PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 22379028-4 2012 Strikingly, a short course of high-dose, but not low-dose, rapamycin treatment transiently blocks viral vaccination-induced mammalian target of rapamycin activity in CD8(+) T cells favoring persistence and Ag-recall responses over type 1 effector maturation; however, prolonged high-dose rapamycin administration abrogated memory responses. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 124-153 22385271-8 2012 Rapamycin, that enhances autophagy by inhibition of mTOR and previously shown to be neuroprotective in our animal model of HI when administered before the ischemic insult, was used to study the potential interaction between autophagy and survival pathways. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 52-56 22564882-9 2012 At variance with rapamycin, dual PI3K/mTOR inhibitors targeted both mTOR complex 1 and mTOR complex 2, and inhibited the rapamycin-resistant phosphorylation of eukaryotic initiation factor 4E-binding protein 1, resulting in a marked inhibition of oncogenic protein translation. Sirolimus 17-26 mechanistic target of rapamycin kinase Homo sapiens 38-42 22564882-9 2012 At variance with rapamycin, dual PI3K/mTOR inhibitors targeted both mTOR complex 1 and mTOR complex 2, and inhibited the rapamycin-resistant phosphorylation of eukaryotic initiation factor 4E-binding protein 1, resulting in a marked inhibition of oncogenic protein translation. Sirolimus 121-130 mechanistic target of rapamycin kinase Homo sapiens 38-42 22457328-2 2012 By assembling with unique and shared partner proteins, mTOR forms the catalytic core of at least two complexes, mTOR complex 1 (mTORC1) and mTORC2, that show differential sensitivity to the allosteric mTOR inhibitor rapamycin and that phosphorylate distinct substrates to modulate cell growth, proliferation, survival, and metabolism in response to diverse environmental cues. Sirolimus 216-225 mechanistic target of rapamycin kinase Homo sapiens 55-59 22457328-2 2012 By assembling with unique and shared partner proteins, mTOR forms the catalytic core of at least two complexes, mTOR complex 1 (mTORC1) and mTORC2, that show differential sensitivity to the allosteric mTOR inhibitor rapamycin and that phosphorylate distinct substrates to modulate cell growth, proliferation, survival, and metabolism in response to diverse environmental cues. Sirolimus 216-225 mechanistic target of rapamycin kinase Homo sapiens 112-116 22457328-2 2012 By assembling with unique and shared partner proteins, mTOR forms the catalytic core of at least two complexes, mTOR complex 1 (mTORC1) and mTORC2, that show differential sensitivity to the allosteric mTOR inhibitor rapamycin and that phosphorylate distinct substrates to modulate cell growth, proliferation, survival, and metabolism in response to diverse environmental cues. Sirolimus 216-225 mechanistic target of rapamycin kinase Homo sapiens 112-116 22167413-0 2012 Single-cell pharmacodynamic monitoring of S6 ribosomal protein phosphorylation in AML blasts during a clinical trial combining the mTOR inhibitor sirolimus and intensive chemotherapy. Sirolimus 146-155 mechanistic target of rapamycin kinase Homo sapiens 131-135 22167413-3 2012 The mTOR signaling pathway is frequently activated in acute myelogenous leukemia (AML) and we previously showed the safety of combining the mTOR inhibitor, sirolimus, with mitoxantrone, etoposide, and cytarabine (MEC) chemotherapy. Sirolimus 156-165 mechanistic target of rapamycin kinase Homo sapiens 4-8 22167413-3 2012 The mTOR signaling pathway is frequently activated in acute myelogenous leukemia (AML) and we previously showed the safety of combining the mTOR inhibitor, sirolimus, with mitoxantrone, etoposide, and cytarabine (MEC) chemotherapy. Sirolimus 156-165 mechanistic target of rapamycin kinase Homo sapiens 140-144 22394614-3 2012 By inhibiting the growth-promoting mTOR pathway, rapamycin decelerates geroconversion of the arrested cells. Sirolimus 49-58 mechanistic target of rapamycin kinase Homo sapiens 35-39 22190165-0 2012 Sorafenib, a multikinase inhibitor, is effective in vitro against non-Hodgkin lymphoma and synergizes with the mTOR inhibitor rapamycin. Sirolimus 126-135 mechanistic target of rapamycin kinase Homo sapiens 111-115 22416776-3 2012 The first identified mTOR inhibitor was rapamycin (sirolimus). Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 21-25 22416776-3 2012 The first identified mTOR inhibitor was rapamycin (sirolimus). Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 21-25 22144101-8 2012 These in vitro findings correlate with our in vivo data showing that inhibition of mTOR by rapamycin injection attenuated the onset of myelination in the early postnatal brain. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 83-87 22193387-6 2012 Similarly, human podocytes treated with the MTOR inhibitor rapamycin accumulated autophagosomes and autophagolysosomes. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 44-48 22170729-6 2012 Everolimus is a rapamycin analog that inhibits mTOR, but it is more soluble than rapamycin and can be administered orally. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 47-51 22357207-8 2012 Ly294002 (a PI3K inhibitor) and rapamycin (an mTOR inhibitor) could prevent the regulatory effects of leptin on the proliferation and apoptosis of HCT-116 cells via abrogating leptin-mediated PI3K/Akt/mTOR pathway. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 46-50 22357207-8 2012 Ly294002 (a PI3K inhibitor) and rapamycin (an mTOR inhibitor) could prevent the regulatory effects of leptin on the proliferation and apoptosis of HCT-116 cells via abrogating leptin-mediated PI3K/Akt/mTOR pathway. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 201-205 22496622-4 2012 Expression of a rapamycin-resistant and kinase-active mTOR (S2035T, mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR (S2035T/D2357E, mTOR-TE), conferred resistance to rapamycin inhibition of LEC tube formation, suggesting that rapamycin inhibition of LEC tube formation is mTOR kinase activity dependent. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 54-58 22496622-4 2012 Expression of a rapamycin-resistant and kinase-active mTOR (S2035T, mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR (S2035T/D2357E, mTOR-TE), conferred resistance to rapamycin inhibition of LEC tube formation, suggesting that rapamycin inhibition of LEC tube formation is mTOR kinase activity dependent. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 68-72 22496622-4 2012 Expression of a rapamycin-resistant and kinase-active mTOR (S2035T, mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR (S2035T/D2357E, mTOR-TE), conferred resistance to rapamycin inhibition of LEC tube formation, suggesting that rapamycin inhibition of LEC tube formation is mTOR kinase activity dependent. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 68-72 22496622-4 2012 Expression of a rapamycin-resistant and kinase-active mTOR (S2035T, mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR (S2035T/D2357E, mTOR-TE), conferred resistance to rapamycin inhibition of LEC tube formation, suggesting that rapamycin inhibition of LEC tube formation is mTOR kinase activity dependent. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 68-72 22496622-4 2012 Expression of a rapamycin-resistant and kinase-active mTOR (S2035T, mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR (S2035T/D2357E, mTOR-TE), conferred resistance to rapamycin inhibition of LEC tube formation, suggesting that rapamycin inhibition of LEC tube formation is mTOR kinase activity dependent. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 68-72 22121221-9 2012 While rapamycin has no effect on overall nucleolar morphology or its proteome, it does induce loss of mTOR and raptor from them. Sirolimus 6-15 mechanistic target of rapamycin kinase Homo sapiens 102-106 22171948-4 2012 Treatment with the mTOR inhibitor rapamycin blocked activation of P70S6K and S6, but it also increased activation of AKT and failed to induce cell death. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 19-23 21898543-5 2012 We found that mTOR inhibition by rapamycin blocks Epo-dependent and -independent osteoblastic phenotypes in human bone marrow stromal cells (hBMSCs) and ST2 cells, respectively. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 14-18 22070140-5 2012 Treatment with the specific mTORC1 [mTOR (mammalian target of rapamycin) complex 1] inhibitor rapamycin or siRNA (small interfering RNA) knockdown of mTOR destabilized the ODC mRNA, but rapamycin had only a minor effect on ODC translation initiation. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 28-32 22070140-5 2012 Treatment with the specific mTORC1 [mTOR (mammalian target of rapamycin) complex 1] inhibitor rapamycin or siRNA (small interfering RNA) knockdown of mTOR destabilized the ODC mRNA, but rapamycin had only a minor effect on ODC translation initiation. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 36-40 22281494-3 2012 However, the inhibition of mTOR activity by rapamycin (inhibitor of several intracellular pathways including S6K1 pathways) reversed the ER stress-reduced tyrosine phosphorylation of IRS-1 and glucose uptake. Sirolimus 44-53 mechanistic target of rapamycin kinase Homo sapiens 27-31 22281494-5 2012 Interestingly, inhibition of mTOR by rapamycin did not affect ER stress markers such as PERK and JNK activity under the ER stress condition. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 29-33 22281494-8 2012 Taken together, these results suggest that rapamycin improved ER stress-induced insulin resistance via inhibition of mTOR/S6K1 hyperphosphorylation in L6 myotubes. Sirolimus 43-52 mechanistic target of rapamycin kinase Homo sapiens 117-121 21742593-3 2012 Rapamycin is an antibiotic inhibiting mTOR. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 38-42 21779001-2 2012 We found that rapamycin, an inhibitor of mTOR complex 1 (mTORC1), attenuated endoplasmic reticulum (ER) stress-induced apoptosis. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 41-45 22262166-1 2012 ATP-competitive mTOR kinase inhibitors (mTorKIs) are a new generation of mTOR-targeted agents with more potent anticancer activity than rapamycin in several tumor models. Sirolimus 136-145 mechanistic target of rapamycin kinase Homo sapiens 16-20 22214523-2 2012 Efficacy varies not so much with drug action, but with tumor type, as different cancer types (and different pre-clinical models) exhibit widely differing susceptibilities to mTOR inhibitors, such as rapamycin. Sirolimus 199-208 mechanistic target of rapamycin kinase Homo sapiens 174-178 20890785-10 2012 Based on these results, neuroblastoma tumor cells are sensitive to treatment with inhibitors of glycolysis, and the demonstrated synergy with rapamycin suggests that the combination of glycolysis and mTOR inhibitors represents a novel therapeutic approach for neuroblastoma that warrants further investigation. Sirolimus 142-151 mechanistic target of rapamycin kinase Homo sapiens 200-204 21993902-7 2012 Moreover, treatment of CML cell line (K562) with rapamycin resulted in a decrease of phosphorylation of mTOR, 4E-BP1 and p70S6K. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 128-132 22028412-6 2012 An inhibitor of mTOR, rapamycin, attenuated the ANG II-stimulated phosphorylation of p70S6K and phosphorylation of IRS-1 (Ser(636/639)) and blocked the ability of ANG II to impair insulin-stimulated phosphorylation of eNOS, nitric oxide production, and mesenteric-arteriole vasodilation. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 16-20 21903859-4 2012 Herein, it is demonstrated that the mammalian target of rapamycin (mTOR) inhibitors rapamycin (sirolimus) and temsirolimus limit both hormone therapy (HT)-sensitive and castration-resistant PCa (CRPC) cell proliferation as single agents and have a profound radiosensitization effect when used in combination with IR. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 36-65 21903859-4 2012 Herein, it is demonstrated that the mammalian target of rapamycin (mTOR) inhibitors rapamycin (sirolimus) and temsirolimus limit both hormone therapy (HT)-sensitive and castration-resistant PCa (CRPC) cell proliferation as single agents and have a profound radiosensitization effect when used in combination with IR. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 67-71 22787661-2 2012 In animal models of TSC and cortical dysplasia, hyperactivation of the mTOR pathway promotes epileptogenesis and neuropathological abnormalities, and the mTOR inhibitor, rapamycin, prevents epilepsy and associated cellular and molecular phenotypes in these models. Sirolimus 170-179 mechanistic target of rapamycin kinase Homo sapiens 154-158 22166573-1 2012 Sirolimus is an approved anti-rejection agent following liver or kidney transplantation that works through inhibition of the mammalian target of rapamycin (mTOR). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 125-154 22166573-1 2012 Sirolimus is an approved anti-rejection agent following liver or kidney transplantation that works through inhibition of the mammalian target of rapamycin (mTOR). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 156-160 22250258-0 2012 A novel application of topical rapamycin formulation, an inhibitor of mTOR, for patients with hypomelanotic macules in tuberous sclerosis complex. Sirolimus 31-40 mechanistic target of rapamycin kinase Homo sapiens 70-74 24116273-3 2012 Here, we report that rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR), reduces the expression of TNF-alpha in rat basophilic leukemia (RBL-2H3) cells. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 56-85 24116273-3 2012 Here, we report that rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR), reduces the expression of TNF-alpha in rat basophilic leukemia (RBL-2H3) cells. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 87-91 23304619-6 2012 CsA was replaced by sirolimus, an mTOR inhibitor, in order to reduce or control the increase in the cyst and liver volume. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 34-38 22059905-6 2012 Rapamycin, the first defined inhibitor of mTOR, showed effectiveness as an anticancer agent in various preclinical models. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 42-46 22614575-7 2012 We review the cutaneous and mucosal toxicities induced by temsirolimus and everolimus, two mTOR inhibitors used as anticancer agents and by their parent molecule sirolimus. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 91-95 22281494-0 2012 Improved insulin sensitivity by rapamycin is associated with reduction of mTOR and S6K1 activities in L6 myotubes. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 74-78 22354768-4 2012 Recent work has shown that treatment with rapamycin, an inhibitor of the mTOR pathway, reduced nuclear blebbing in HGPS fibroblasts. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 73-77 22043997-7 2012 Pharmacologic inhibition of mTOR using rapamycin or ridaforolimus increased lapatinib sensitivity and reduced phospho-Akt levels in cells that showed poor response to single-agent lapatinib, including those transfected with hyperactive Akt. Sirolimus 39-48 mechanistic target of rapamycin kinase Homo sapiens 28-32 21567173-3 2012 We show for the first time that in THP-1-derived macrophages and human monocytes, mTOR inhibition by rapamycin reversed L. donovani-induced IL-12 and IL-10 modulation. Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 82-86 21567173-5 2012 This increase in P70S6K phosphorylation was completely blocked by rapamycin (mTOR inhibitor) and partially by wortmannin (PI3K inhibitor). Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 77-81 22084168-2 2012 Here, we investigated whether rapamycin, an mTOR inhibitor, increased the sensitivity to doxorubicin therapy in two HER-2-overexpressing cell lines: C5.2, which was derived from the parental HB4a by transfection with HER-2 and SKBR3, which exhibits HER-2 amplification. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 44-48 22080480-2 2012 Rapamycin analogs, which are allosteric mTOR complex 1 (mTORC1) inhibitors, are active in mantle cell lymphoma and other lymphoid neoplasms, but responses are usually partial and short-lived. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 40-44 22214188-8 2012 In contrast, the mTOR inhibitor rapamycin enhanced both COX-2 and mPGES-1 immunoreactivity and the release of PGE2 and PGD2. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 17-21 23082251-1 2012 Effects of the mTOR inhibitor rapamycin were characterized on in vitro cultured primary human acute myeloid leukemia (AML) cells and five AML cell lines. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 15-19 23082251-8 2012 To conclude, (i) pharmacological characterization of PI3K-Akt-mTOR inhibitors requires carefully standardized experimental models, (ii) rapamycin effects differ between patients, and (iii) combined targeting of different steps in this pathway should be further investigated whereas combination of rapamycin with valproic acid, ATRA, or NF-kappaB inhibitors seems less promising. Sirolimus 136-145 mechanistic target of rapamycin kinase Homo sapiens 62-66 22619555-2 2012 Sirolimus, an inhibitor of mammalian target of rapamycin has gained attention for targeted anticancer therapy, but its clinical application has been limited by its poor solubility. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-56 22030071-8 2012 Rapamycin is a macrolide that, besides its antiepileptic effect, restores the Akt function and inhibits the mTOR pathway which may have an antidepressant effect. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 108-112 21980128-5 2011 Targeting mTOR and EGFR pathways by treatment with rapamycin and cetuximab (an anti-EGFR mAb), respectively, prevented cixutumumab-induced expression of EGFR, Akt, and survivin and induced synergistic antitumor effects in vitro and in vivo. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 10-14 22125057-0 2012 Biochemical and pharmacological inhibition of mTOR by rapamycin and an ATP-competitive mTOR inhibitor. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 46-50 22125063-6 2012 Moreover, the mTORC2 complex components rictor and sin1 are dephosphorylated and dynamically distributed between the cytoplasm and the nucleus upon long-term treatment with the mTOR-inhibitor rapamycin. Sirolimus 192-201 mechanistic target of rapamycin kinase Homo sapiens 14-18 22125064-2 2012 Constitutive mTOR signaling characterizes multiple human malignancies, and pharmacological inhibitors of mTOR such as the immunosuppressant rapamycin and some of its nonimmunosuppressive derivatives not only have been ascribed with promising anticancer properties in vitro and in vivo but are also being extensively evaluated in clinical trials. Sirolimus 140-149 mechanistic target of rapamycin kinase Homo sapiens 13-17 22125064-2 2012 Constitutive mTOR signaling characterizes multiple human malignancies, and pharmacological inhibitors of mTOR such as the immunosuppressant rapamycin and some of its nonimmunosuppressive derivatives not only have been ascribed with promising anticancer properties in vitro and in vivo but are also being extensively evaluated in clinical trials. Sirolimus 140-149 mechanistic target of rapamycin kinase Homo sapiens 105-109 22479189-10 2012 Combination treatment using roscovitine (CDK inhibitor) plus either rapamycin (mTOR inhibitor) or sorafenib (a pan kinase inhibitor targeting b-Raf) effectively prevented aberrant acinar formation in LMW-E-expressing cells by inducing G1/S cell cycle arrest. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 79-83 22479189-12 2012 The b-Raf-ERK1/2-mTOR signaling pathway is aberrantly activated in breast cancer and can be suppressed by combination treatment with roscovitine plus either rapamycin or sorafenib. Sirolimus 157-166 mechanistic target of rapamycin kinase Homo sapiens 17-21 23071528-9 2012 Low dose oral sirolimus increases the risk of menstrual cycle disturbances and ovarian cysts and monitoring of sirolimus-associated ovarian toxicity is warranted and might guide clinical practice with mammalian target of rapamycin inhibitors. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 201-230 23071528-9 2012 Low dose oral sirolimus increases the risk of menstrual cycle disturbances and ovarian cysts and monitoring of sirolimus-associated ovarian toxicity is warranted and might guide clinical practice with mammalian target of rapamycin inhibitors. Sirolimus 111-120 mechanistic target of rapamycin kinase Homo sapiens 201-230 22900063-3 2012 Here we show that elevated VEGF levels produced by hemangioma endothelial cells are reduced by the mTOR inhibitor rapamycin. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 99-103 22848663-5 2012 HBx upregulated cell proliferation and vascular endothelial growth factor (VEGF) production, and these HBx-upregulated phenotypes were abolished by treatment with IKKbeta inhibitor Bay 11-7082 or mTOR inhibitor rapamycin. Sirolimus 211-220 mechanistic target of rapamycin kinase Homo sapiens 196-200 20207175-2 2012 Rapamycin, the inhibitor of mTOR Complex 1, provides alternative immunosuppressive therapy after kidney transplantation with less neoplastic potential. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 28-32 21994950-4 2011 The ORF45/RSK-mediated eIF4B phosphorylation was distinguishable from that caused by the canonical AKT/mammalian target of rapamycin/ribosomal S6 kinase and MEK/ERK/RSK pathways because it was resistant to both rapamycin (an mammalian target of rapamycin inhibitor) and U1026 (an MEK inhibitor). Sirolimus 123-132 mechanistic target of rapamycin kinase Homo sapiens 225-254 20828737-9 2011 Pretreatment with rapamycin, a specific inhibitor of mTOR, resulted in a significant decrease of IL-10 and IL-6 translation and expression but did not affect the LPS-induced TNFalpha production. Sirolimus 18-27 mechanistic target of rapamycin kinase Homo sapiens 53-57 22057915-1 2012 Inhibition of mTOR signaling by rapamycin has been shown to activate extracellular signal-regulated kinase 1 or 2 (ERK1/2) and Akt in various types of cancer cells, which contributes to rapamycin resistance. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 14-18 22057915-1 2012 Inhibition of mTOR signaling by rapamycin has been shown to activate extracellular signal-regulated kinase 1 or 2 (ERK1/2) and Akt in various types of cancer cells, which contributes to rapamycin resistance. Sirolimus 186-195 mechanistic target of rapamycin kinase Homo sapiens 14-18 22015781-9 2011 Inhibition of mTOR with rapamycin reversed the down-regulation of cellular lipid efflux mediator ABCA1, which resulted from the activation of TLR4 by ligands. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 14-18 21889928-8 2011 Importantly, co-treatment with MEK/ERK inhibitor (U0126) and PI3K/Akt (LY294002) or mTOR (rapamycin) inhibitors, instead of ATO, also potentiates lonidamine-provoked apoptosis. Sirolimus 90-99 mechanistic target of rapamycin kinase Homo sapiens 84-88 21438065-1 2011 BACKGROUND: Rapamycin is an mTOR inhibitor with preclinical efficacy in squamous cell carcinoma of the head and neck (SCCHN). Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 28-32 22091684-1 2011 Sirolimus (SRL) is a mammalian target of rapamycin inhibitor, which provides an immunosuppressive effect by inhibiting cell cycle progression. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 21-50 21445948-5 2011 PROCEDURE: Here we retrospectively evaluate a series of six patients with complicated, life-threatening vascular anomalies who were treated with the mTOR inhibitor sirolimus for compassionate use at two centers after failing multiple other therapies. Sirolimus 164-173 mechanistic target of rapamycin kinase Homo sapiens 149-153 22071574-0 2011 High-dose rapamycin induces apoptosis in human cancer cells by dissociating mTOR complex 1 and suppressing phosphorylation of 4E-BP1. Sirolimus 10-19 mechanistic target of rapamycin kinase Homo sapiens 76-80 22071574-5 2011 We report here that the apoptotic effects of high-dose rapamycin treatment correlate with suppressing phosphorylation of the mTOR complex 1 substrate, eukaryotic initiation factor 4E (eIF4E) binding protein-1 (4E-BP1). Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 125-129 22074495-11 2011 Finally, the mTOR inhibitor Rapamycin enhanced the effect of GSI on RhoA expression, resulting in down regulation of phospho-Akt and increased in vitro tumor cytotoxity. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 13-17 21946849-2 2011 Since rapamycin is considered to be a highly specific inhibitor of the mammalian target of rapamycin (mTOR), many have concluded that mTOR plays a key role in CML-induced growth regulatory events. Sirolimus 6-15 mechanistic target of rapamycin kinase Homo sapiens 71-100 21946849-2 2011 Since rapamycin is considered to be a highly specific inhibitor of the mammalian target of rapamycin (mTOR), many have concluded that mTOR plays a key role in CML-induced growth regulatory events. Sirolimus 6-15 mechanistic target of rapamycin kinase Homo sapiens 102-106 21946849-2 2011 Since rapamycin is considered to be a highly specific inhibitor of the mammalian target of rapamycin (mTOR), many have concluded that mTOR plays a key role in CML-induced growth regulatory events. Sirolimus 6-15 mechanistic target of rapamycin kinase Homo sapiens 134-138 21883182-17 2011 The mammalian target of rapamycin (mTOR) signaling pathway might be a useful drug target for influencing GABAergic synaptic reorganization after epileptogenic treatments, but additional side effects of rapamycin treatment must be considered carefully. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 35-39 21602892-6 2011 Blocking mTOR kinase activity via rapamycin and its activation in TSC2(-/-) cells and via TSC2 small interfering RNAs revealed that it regulates the localization of p70, but not of p85 and p31. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 9-13 21890461-7 2011 Altered regulation of mTOR pathway proteins in BPA-treated HRBECs led to marked resistance to rapamycin, the defining mTOR inhibitor. Sirolimus 94-103 mechanistic target of rapamycin kinase Homo sapiens 22-26 21890461-7 2011 Altered regulation of mTOR pathway proteins in BPA-treated HRBECs led to marked resistance to rapamycin, the defining mTOR inhibitor. Sirolimus 94-103 mechanistic target of rapamycin kinase Homo sapiens 118-122 22037041-2 2011 Rapamycin is an allosteric inhibitor of mTOR, and was approved as an immuno-suppressant in 1999. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 40-44 21945951-8 2011 Furthermore, p53 activation by AICAR was blocked by rapamycin, a specific inhibitor of the mTOR kinase, which is a crucial regulator of cell growth. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 91-95 21968016-8 2011 Rapamycin, the pharmacologic inhibitor of mammalian target of rapamycin (mTOR), diminished NGF-induced S6 phosphorylation, cell migration and protective effects against oxidative stress. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 42-71 21968016-8 2011 Rapamycin, the pharmacologic inhibitor of mammalian target of rapamycin (mTOR), diminished NGF-induced S6 phosphorylation, cell migration and protective effects against oxidative stress. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 73-77 22737268-3 2011 Demonstrated herein, we have shown that both the development and growth of metastatic lesions are markedly reduced by the mTOR inhibitor sirolimus. Sirolimus 137-146 mechanistic target of rapamycin kinase Homo sapiens 122-126 21302298-6 2011 The effects of TGFbeta and bleomycin on ECM synthesis were blunted by pre-treatment with an mTOR inhibitor rapamycin. Sirolimus 107-116 mechanistic target of rapamycin kinase Homo sapiens 92-96 21854819-5 2011 The insulin-induced increase of tau protein level was abolished by LY294002 [an inhibitor of phosphoinositide 3-kinase (PI3K)] and rapamycin [an inhibitor of mammalian target of rapamycin (mTOR)], but not by PD98059 and U0126 [two inhibitors of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK)]. Sirolimus 131-140 mechanistic target of rapamycin kinase Homo sapiens 158-187 21854819-5 2011 The insulin-induced increase of tau protein level was abolished by LY294002 [an inhibitor of phosphoinositide 3-kinase (PI3K)] and rapamycin [an inhibitor of mammalian target of rapamycin (mTOR)], but not by PD98059 and U0126 [two inhibitors of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK)]. Sirolimus 131-140 mechanistic target of rapamycin kinase Homo sapiens 189-193 22099798-5 2011 OBJECTIVE: The aim was to evaluate the cost-effectiveness of early conversion from tacrolimus to mammalian target of rapamycin inhibitors sirolimus or everolimus versus continuous treatment with tacrolimus among renal transplantat patients in Colombia. Sirolimus 138-147 mechanistic target of rapamycin kinase Homo sapiens 97-126 21825008-1 2011 Ridaforolimus is a nonprodrug rapamycin analogue that potently inhibits mTOR and has shown significant activity in patients with metastatic sarcoma and endometrial cancer, two diseases where high unmet need remains. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 72-76 22016125-8 2011 Calcineurin inhibitors (cyclosporine, tacrolimus) and mTOR inhibitors (sirolimus, everolimus) are particularly susceptible to the effects of substances that inhibit or induce cytochrome P450 (CYP) 3A4 and P-glycoprotein. Sirolimus 71-80 mechanistic target of rapamycin kinase Homo sapiens 54-58 21128236-3 2011 We found that, despite showing no effect on HSV replication in tumor cells fully permissive to the virus growth, the mTOR inhibitor rapamycin markedly increased the yield and dissemination of oncolytic HSVs in semipermissive tumor cells. Sirolimus 132-141 mechanistic target of rapamycin kinase Homo sapiens 117-121 21862955-1 2011 BACKGROUND: The mammalian target of rapamycin inhibitor sirolimus has been associated with an increased incidence of wound-healing complications after de novo heart transplantation. Sirolimus 56-65 mechanistic target of rapamycin kinase Homo sapiens 16-45 21524191-1 2011 The goal of this study was to assess the interaction of the mTOR inhibitors (ImTORs) sirolimus and everolimus with the human organic anion-transporting polypeptides (OATPs) expressed in hepatocytes and enterocytes by conducting uptake experiments using (i) transfected HEK293T cells, (ii) the hepatocyte-like HepaRG cell line and (iii) the enterocyte-like Caco-2 cell line. Sirolimus 85-94 mechanistic target of rapamycin kinase Homo sapiens 60-64 21984149-10 2011 Rapamycin significantly inhibited mTOR signaling upstream Akt and downstream S6K activation triggered by IDA, and the combination of the two agents led to synergistic inhibition of ERK phosphorylation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 34-38 21690574-7 2011 PM02734 caused inhibition of Akt/mTOR signaling pathways and cotreatment with the Akt inhibitor wortmannin or with the mTOR inhibitor rapamycin led to a significant increase in PM02734-induced cell death. Sirolimus 134-143 mechanistic target of rapamycin kinase Homo sapiens 33-37 21690574-7 2011 PM02734 caused inhibition of Akt/mTOR signaling pathways and cotreatment with the Akt inhibitor wortmannin or with the mTOR inhibitor rapamycin led to a significant increase in PM02734-induced cell death. Sirolimus 134-143 mechanistic target of rapamycin kinase Homo sapiens 119-123 21480865-8 2011 ACEA, JWH133 and HU210 induced a time-dependent phosphorylation of Akt and mTOR, whereas the inhibitors of PI3K/Akt (LY294002) or of mTOR (rapamycin) reversed the effects of HU-210 on oligodendrocyte differentiation and kinase activation. Sirolimus 139-148 mechanistic target of rapamycin kinase Homo sapiens 133-137 21827982-4 2011 Thereby, mTOR inhibition with rapamycin (sirolimus) or its derivates (rapalogs) represents promising treatments, either alone or in combination with strategies to target other pathways that may overcome resistance. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 9-13 21827982-4 2011 Thereby, mTOR inhibition with rapamycin (sirolimus) or its derivates (rapalogs) represents promising treatments, either alone or in combination with strategies to target other pathways that may overcome resistance. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 9-13 21168455-0 2011 Potent antifibrotic activity of mTOR inhibitors sirolimus and everolimus but not of cyclosporine A and tacrolimus in experimental liver fibrosis. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 32-36 21168455-7 2011 CONCLUSIONS: mTOR inhibition by sirolimus and everolimus in experimental liver fibrosis associates with significantly less fibrosis progression and portal hypertension than treatment with calcineurin inhibitors tacrolimus and cyclosporine A. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 13-17 21690228-6 2011 The combination of EGFR inhibition by using lapatinib and mTOR inhibition with rapamycin resulted in significantly greater cytotoxicity than the single agents alone and these effects were synergistic in vitro. Sirolimus 79-88 mechanistic target of rapamycin kinase Homo sapiens 58-62 21772323-3 2011 By inhibiting the activity of mammalian target of rapamycin (mTOR), rapamycin influences a variety of essential cellular processes, such as cell growth and proliferation, protein synthesis and autophagy. Sirolimus 50-59 mechanistic target of rapamycin kinase Homo sapiens 61-65 21613408-7 2011 Finally, X-396 displayed synergistic growth inhibitory activity when combined with the mTOR inhibitor rapamycin. Sirolimus 102-111 mechanistic target of rapamycin kinase Homo sapiens 87-91 21742783-3 2011 In vitro cigarette smoke extract (CSE) and one of its components, acrolein, inhibit the mammalian target of rapamycin (mTOR)/p70S6K pathway in human endothelial cells, and chemical inhibition of this pathway by rapamycin resulted in elevated MMP-1. Sirolimus 108-117 mechanistic target of rapamycin kinase Homo sapiens 119-123 21440356-6 2011 mTOR inhibitor sirolimus reduces angymiolipoma volumes. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 0-4 21862872-6 2011 Trastuzumab-resistant sublines were resistant to rapamycin induced changes in mTOR activity and cell growth. Sirolimus 49-58 mechanistic target of rapamycin kinase Homo sapiens 78-82 21702716-3 2011 So far, specific mTOR inhibitors, such as rapamycin analogs, have been developed and studied as anti-cancer agents. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 17-21 21702716-5 2011 EXPERT OPINION: In the near future, mTOR-targeted drugs might represent a new approach for the therapy of thyroid cancer patients; rapamycin analogs have already been developed and are currently being clinically tested. Sirolimus 131-140 mechanistic target of rapamycin kinase Homo sapiens 36-40 21336564-0 2011 Combined inhibition of PI3K and mTOR exerts synergistic antiproliferative effect, but diminishes differentiative properties of rapamycin in acute myeloid leukemia cells. Sirolimus 127-136 mechanistic target of rapamycin kinase Homo sapiens 32-36 21336564-5 2011 These results demonstrate that, although the combination of PI3K inhibitor and rapamycin is more effective in inhibiting proliferation of AML, the concomitant inhibition of PI3K and mTOR by LY 294002 and rapamycin has more inhibitory effects on ATRA-mediated differentiation than the presence of PI3K-inhibitor alone, and diminishes positive effects of rapamycin on leukemia cell differentiation. Sirolimus 204-213 mechanistic target of rapamycin kinase Homo sapiens 182-186 21911134-2 2011 Newer immunosuppressants such as mycophenolic acid and, particularly, mammalian target of rapamycin (mTOR) inhibitors (eg, sirolimus) may cause significant lung toxicity. Sirolimus 123-132 mechanistic target of rapamycin kinase Homo sapiens 70-99 21911134-2 2011 Newer immunosuppressants such as mycophenolic acid and, particularly, mammalian target of rapamycin (mTOR) inhibitors (eg, sirolimus) may cause significant lung toxicity. Sirolimus 123-132 mechanistic target of rapamycin kinase Homo sapiens 101-105 21252047-6 2011 In the presence of rapamycin, a specific mTOR inhibitor, leptin and PDGF were no longer able to activate mTOR, and expression of VEGF was reduced, whereas HIF-1alpha abundance was not affected. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 41-45 21252047-6 2011 In the presence of rapamycin, a specific mTOR inhibitor, leptin and PDGF were no longer able to activate mTOR, and expression of VEGF was reduced, whereas HIF-1alpha abundance was not affected. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 105-109 21305305-7 2011 Biologically targeted pharmacotherapy with mTOR inhibitors such as sirolimus and everolimus provides a safe and efficacious treatment option for patients with SGCT and has the potential to change the clinical management of these tumors. Sirolimus 67-76 mechanistic target of rapamycin kinase Homo sapiens 43-47 21508335-4 2011 Here, we demonstrate that the inhibition of mTORC1 by rapamycin (mTORC1 inhibitor), torin1 (both mTORC1 and mTORC2 inhibitor) or short hairpin RNA-mediated knockdown of mTOR, regulatory associated protein of mTOR (RAPTOR), and p70 S6 kinase (p70S6K) increased basal NT release via upregulating NT gene expression in BON cells. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 44-48 21600903-1 2011 AIMS: Rapamycin (sirolimus) is an antibiotic that inhibits protein synthesis through mammalian targeting of rapamycin (mTOR) signaling, and is used as an immunosuppressant in the treatment of organ rejection in transplant recipients. Sirolimus 6-15 mechanistic target of rapamycin kinase Homo sapiens 119-123 21600903-1 2011 AIMS: Rapamycin (sirolimus) is an antibiotic that inhibits protein synthesis through mammalian targeting of rapamycin (mTOR) signaling, and is used as an immunosuppressant in the treatment of organ rejection in transplant recipients. Sirolimus 17-26 mechanistic target of rapamycin kinase Homo sapiens 119-123 21501360-3 2011 Treatment of human epithelial HeLa cells with mTOR inhibitor rapamycin reduced lysosomal exocytosis and MT invasion. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 46-50 20686837-6 2011 Further analysis demonstrated that the combination of the mTOR inhibitor rapamycin and cisplatin generated significant drug synergism in basal-like MDA-MB-468, MDA-MB-231, and HCC1937 cells but not in luminal-like T47D or MCF-7 cells. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 58-62 21602434-4 2011 At the molecular level, combined inhibition of mTOR prevented the rebound activation of Akt that is seen after treatment with rapamycin and its analogues and caused more sustained inhibition of Akt phosphorylation. Sirolimus 126-135 mechanistic target of rapamycin kinase Homo sapiens 47-51 21415215-8 2011 Inhibition of the mTOR catalytic site with OSI-027 results in suppression of both mTORC2 and RI-mTORC1 complexes and elicits much more potent antileukemic responses than selective mTORC1 targeting with rapamycin. Sirolimus 202-211 mechanistic target of rapamycin kinase Homo sapiens 18-22 21561413-2 2011 mTOR complex 1 (mTORC1) is potently inhibited by the immunosupressive macrolide rapamycin; whereas, mTORC2 is insensitive to this durg. Sirolimus 80-89 mechanistic target of rapamycin kinase Homo sapiens 0-4 21576371-5 2011 Rapamycin exposure destabilizes mTORC1, but in cell lines where autophagy is drug insensitive, higher levels of mTOR-bound raptor are detected than in cells where rapamycin stimulates autophagy. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 32-36 21633171-2 2011 Mammalian TOR (mTOR) is thought to work through 2 independent complexes to regulate cell size and cell replication, and these 2 complexes show differential sensitivity to rapamycin. Sirolimus 171-180 mechanistic target of rapamycin kinase Homo sapiens 15-19 21488160-3 2011 Sirolimus (rapamysin) inhibits the serine-threonine kinase mammalian target of rapamysin (mTOR), and blocks CsA-resistant and calcium-independent pathways late in the progression of the T-cell cycle. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 90-94 21730367-5 2011 Cells which expressed Akt-1(CA) were hypersensitive to the mTOR inhibitor rapamycin. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 60-64 21730367-6 2011 Furthermore, rapamycin lowered the IC50s for doxorubicin, etoposide and 4HT in the cells which expressed Akt-1(CA), demonstrating a potential improved method for treating certain breast cancers which have deregulated PI3K/PTEN/Akt/mTOR signaling. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 232-236 21418335-5 2011 The impact of immunosuppression and especially immunosuppression with mammalian target of rapamycin (mTOR) inhibitors on the development of surgical wound complications has been widely discussed following reports of increased occurrence with sirolimus. Sirolimus 242-251 mechanistic target of rapamycin kinase Homo sapiens 70-99 21418335-5 2011 The impact of immunosuppression and especially immunosuppression with mammalian target of rapamycin (mTOR) inhibitors on the development of surgical wound complications has been widely discussed following reports of increased occurrence with sirolimus. Sirolimus 242-251 mechanistic target of rapamycin kinase Homo sapiens 101-105 21715609-5 2011 Interestingly, rapamycin (a Food and Drug Administration-approved drug) restores normal levels of phosphorylated Akt-mTOR proteins and normal rates of local translation in Ts1Cje neurons, opening new therapeutic perspectives for DS. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 117-121 21690594-3 2011 Sirolimus is a mammalian target of rapamycin inhibitor that has been reported to decrease the size of neoplastic growths in animal models of tuberous sclerosis complex and to reduce the size of angiomyolipomas and stabilize lung function in humans. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 15-44 21665152-1 2011 Angioproliferative tumors induced by the Kaposi"s sarcoma-associated herpesvirus (KSHV) have been successfully treated with rapamycin, which provided direct evidence of the clinical activity of mTOR inhibitors in human malignancies. Sirolimus 124-133 mechanistic target of rapamycin kinase Homo sapiens 194-198 21316758-3 2011 Potentiated ATP depletion and pro-apoptotic effects were seen for 3-BrOP combinations with the cytochrome-c-reductase inhibitor antimycin A and the mTOR inhibitor rapamycin. Sirolimus 163-172 mechanistic target of rapamycin kinase Homo sapiens 148-152 20715103-5 2011 Simultaneous inhibition of VEGFR downstream effector mTOR using rapamycin 20 mg/kg q2dx5 did not statistically enhance tumor growth delay compared to single agent activities. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 53-57 21557327-4 2011 mTOR exists in two distinct complexes-mTORC1 and mTORC2 that differ in their components and sensitivity to rapamycin. Sirolimus 107-116 mechanistic target of rapamycin kinase Homo sapiens 0-4 21318349-8 2011 The specific mTOR inhibitor rapamycin (10 nM) attenuated leptin-induced RhoA and Rac1 activation. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 13-17 21089180-5 2011 Chrysophanic acid (80 and 120 microm) significantly blocked cell proliferation when combined with the mTOR inhibitor, rapamycin. Sirolimus 118-127 mechanistic target of rapamycin kinase Homo sapiens 102-106 21478152-5 2011 Activation of AMPK with 5-aminoimidazole-4-carbozamide-1-beta-D-ribifuranoside or inhibition of mTOR with rapamycin or mTOR siRNA attenuated these resistin-induced changes. Sirolimus 106-115 mechanistic target of rapamycin kinase Homo sapiens 96-100 21541789-3 2011 Sirolimus and its derivatives (rapalogs) interact with the intracellular receptor FK506 binding protein 12 (FKBP12), forming a complex with high affinity for mTOR and thus disrupting its activity. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 158-162 21478152-8 2011 Resistin also stimulated the activation of p70(S6K), a downstream kinase target of mTOR, and increased phosphorylation of the IRS1 serine 636/639 residues, whereas treatment with rapamycin reduced the phosphorylation of these residues. Sirolimus 179-188 mechanistic target of rapamycin kinase Homo sapiens 83-87 21572994-5 2011 The expression of IFN-gammainduced by IL-12 and IL-18 is sensitive to rapamycin and SB203580, indicating the possible involvement of mTOR and p38 MAP kinase, respectively, in this synergistic pathway. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 133-137 21576264-5 2011 CPT1C expression correlates inversely with mammalian target of rapamycin (mTOR) pathway activation, contributes to rapamycin resistance in murine primary tumors, and is frequently up-regulated in human lung tumors. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 74-78 24212820-2 2011 Knowledge in this field has been gained from discoveries in basic research as well as from observations made in patients treated with allosteric mTOR inhibitors such as rapamycin. Sirolimus 169-178 mechanistic target of rapamycin kinase Homo sapiens 145-149 21521942-11 2011 The failure to limit mTOR-dependent induction of HIF-1 may contribute to age-related macular degeneration and diabetic retinopathy, suggesting rapamycin for prevention of these age-related diseases. Sirolimus 143-152 mechanistic target of rapamycin kinase Homo sapiens 21-25 21228102-4 2011 Both GSK3 inhibitors reduced the phosphorylation of the mTOR downstream target, p70(S6K), indicating that GSK3 inhibition in podocytes is able to cause similar effects as treatment with rapamycin. Sirolimus 186-195 mechanistic target of rapamycin kinase Homo sapiens 56-60 21329734-6 2011 Inhibition of the mTOR pathway by rapamycin eliminated the angiogenic and proliferative effects of visfatin. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 18-22 21243421-1 2011 The tuberous sclerosis complex 1/2-mammalian target of rapamycin (TSC1/2-mTOR) proteins act as integrators of a range of intracellular signalling pathways. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 73-77 20680277-9 2011 In addition, ROS generation was included in downstream signaling events associated with the phosphorylation of mTOR, because pretreatment of cells with rapamycin inhibited ROS generation. Sirolimus 152-161 mechanistic target of rapamycin kinase Homo sapiens 111-115 21203833-8 2011 Addition of rapamycin, an inhibitor of mTOR, caused stimulation of the MG-132-induced cell death. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 39-43 21520111-1 2011 OBJECTIVES/HYPOTHESIS: To evaluate antitumor efficacy of the generic mammalian target of rapamycin (mTOR) inhibitor sirolimus in preclinical animal models of head and neck squamous cell carcinoma (HNSCC) and compare its effects with those of the patented analogue temsirolimus. Sirolimus 116-125 mechanistic target of rapamycin kinase Homo sapiens 69-98 21520111-1 2011 OBJECTIVES/HYPOTHESIS: To evaluate antitumor efficacy of the generic mammalian target of rapamycin (mTOR) inhibitor sirolimus in preclinical animal models of head and neck squamous cell carcinoma (HNSCC) and compare its effects with those of the patented analogue temsirolimus. Sirolimus 116-125 mechanistic target of rapamycin kinase Homo sapiens 100-104 21520111-12 2011 CONCLUSIONS: In this study, we demonstrate that the generic mTOR inhibitor sirolimus shows potent antitumor activity in HNSCC and produces comparable effects to the patent drug temsirolimus. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 60-64 21127480-4 2011 The kinases AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) are each linked to food intake regulation, but only mTOR had increased activity in KSR2(-/-) mouse brain, and the ability of rapamycin to inhibit food intake in KSR2(-/-) mice further implicated mTOR in this process. Sirolimus 72-81 mechanistic target of rapamycin kinase Homo sapiens 83-87 21304100-8 2011 Blocking of mTOR with rapamycin suppressed the maturation of neonatal MKs without affecting ploidy, in contrast to the synchronous inhibition of polyploidization and cytoplasmic maturation in adult MKs. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 12-16 21511183-5 2011 The ability of rapamycin to augment HP-induced memory was cell-intrinsic given that silencing mTOR in CD8+ T cells generated identical outcomes. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 94-98 21410393-2 2011 Sirolimus (also called rapamycin) inhibits mTOR and has shown promise in phase 1-2 trials involving patients with LAM. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 43-47 21410393-2 2011 Sirolimus (also called rapamycin) inhibits mTOR and has shown promise in phase 1-2 trials involving patients with LAM. Sirolimus 23-32 mechanistic target of rapamycin kinase Homo sapiens 43-47 21439267-2 2011 Indeed, the inhibition of mTOR with an allosteric inhibitor such as rapamycin reduces the growth of endothelial cell in vitro and inhibits angiogenesis in vivo. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 26-30 21439267-5 2011 Here we found that blocking mTOR with ATP-competitive inhibitors of mTOR or with rapamycin induced the activation of the mitogen-activated protein kinase (MAPK) in endothelial cells. Sirolimus 81-90 mechanistic target of rapamycin kinase Homo sapiens 28-32 21367753-5 2011 Rapamycin effectively modulated the protein kinase B (Akt)/mTOR pathway by inhibiting the phosphorylation of Akt and mTOR proteins, and this inhibition was further enhanced by radiation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 59-63 21367753-5 2011 Rapamycin effectively modulated the protein kinase B (Akt)/mTOR pathway by inhibiting the phosphorylation of Akt and mTOR proteins, and this inhibition was further enhanced by radiation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 117-121 21446969-4 2011 Here, we review recent findings concerning the contradictory outcomes of rapamycin induced mTOR inhibition on CD4(+) and CD8(+) T cell responses in transplantation and protective immunity. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 91-95 21138727-3 2011 To demonstrate, we characterized the binding of polyketide ligands based on the mTOR inhibitor rapamycin to the cellular immunophilin FKBP12. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 80-84 21447721-1 2011 PURPOSE: Sirolimus is the prototypical mTOR inhibitor. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 39-43 21428917-2 2011 Rapamycin inhibits some of the functions of mTORC1, whereas newly developed mTOR kinase inhibitors interfere with the actions of both types of complex. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 44-48 21428919-2 2011 The present review highlights molecular and phenotypic differences between AZD8055 and allosteric inhibitors of mTOR such as rapamycin. Sirolimus 125-134 mechanistic target of rapamycin kinase Homo sapiens 112-116 21277936-7 2011 Functional studies using rapamycin or CCI-779 showed a dominant inhibitory effect of mTOR blockade on interleukin-7-induced proliferation, survival, and cell-cycle progression of T-ALL cells. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 85-89 21451536-2 2011 The Spare the Nephron Trial describes the popular approach of early conversion from a CNI to the mTOR agent sirolimus for patients maintained on mycophenolate mofetil and steroids. Sirolimus 108-117 mechanistic target of rapamycin kinase Homo sapiens 97-101 21406405-4 2011 Inhibition of MNK1 activity in GBM cells by the small molecule CGP57380 suppressed eIF4E phosphorylation, proliferation, and colony formation whereas concomitant treatment with CGP57380 and the mTOR inhibitor rapamycin accentuated growth inhibition and cell-cycle arrest. Sirolimus 209-218 mechanistic target of rapamycin kinase Homo sapiens 194-198 21415462-1 2011 Rapamycin inhibits the mTOR (target of rapamycin) pathway and extends lifespan in multiple species. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 23-27 20714941-2 2011 DISCUSSION: Sirolimus is a mTOR inhibitor which has been used as an immunosuppressive medication in patients who are at high risk of tumor reoccurrence after liver transplantation. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 27-31 21308356-7 2011 For chronic GvHD mTOR inhibitors (sirolimus, everolimus) may replace calcineurin-inhibitors with the advantage of not inducing malignant skin tumors. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 17-21 21350938-6 2011 We also tested whether inhibition of mTOR with low concentrations of rapamycin and ectopic Beclin-1 expression would further sensitize multidrug resistance (MDR)-positive cancer cells by upregulating autophagy. Sirolimus 69-78 mechanistic target of rapamycin kinase Homo sapiens 37-41 21168265-0 2011 Resveratrol enhances the anti-tumor activity of the mTOR inhibitor rapamycin in multiple breast cancer cell lines mainly by suppressing rapamycin-induced AKT signaling. Sirolimus 67-76 mechanistic target of rapamycin kinase Homo sapiens 52-56 21168265-0 2011 Resveratrol enhances the anti-tumor activity of the mTOR inhibitor rapamycin in multiple breast cancer cell lines mainly by suppressing rapamycin-induced AKT signaling. Sirolimus 136-145 mechanistic target of rapamycin kinase Homo sapiens 52-56 21629335-2 2011 Constant and inadequate proliferation occurring in TS may be blocked by mTOR inhibitors (mammalian target of rapamycin), such as rapamycin. Sirolimus 109-118 mechanistic target of rapamycin kinase Homo sapiens 72-76 21651476-4 2011 Rapamycin, the selective and allosteric inhibitor of mTOR, inhibits the enzyme in mTORC1, but not in mTORC2. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 53-57 21745772-4 2011 Rapamycin is an immunosupressor used in transplanted patients that inhibits the mTOR transduction signal pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 80-84 21320304-1 2011 BACKGROUND: Inhibitors of the kinase mTOR, such as rapamycin and everolimus, have been used as cancer therapeutics with limited success since some tumours are resistant. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 37-41 20625781-6 2011 Experiments with the mTOR inhibitor rapamycin revealed that neither blocking the phosphorylation of S6 at S235/236 and S240/244 nor arresting the cell cycle affects the cytoplasmic/nuclear localization of S6 protein. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 21-25 20594757-11 2011 Inhibition of mTOR by rapamycin inhibited the phosphorylation of mTOR, reduced serine307 phosphorylation, elevated tyrosine phosphorylation and partly prevented the decrease of GIR after burn. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 20594757-11 2011 Inhibition of mTOR by rapamycin inhibited the phosphorylation of mTOR, reduced serine307 phosphorylation, elevated tyrosine phosphorylation and partly prevented the decrease of GIR after burn. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 65-69 20940044-5 2011 We found that Li(+) activated the mammalian target of rapamycin (mTOR) pathway via GSK-3beta in these cells, and the effect of Li(+) to induce c-Ret was amenable to the inhibitory effect of the mTOR inhibitor, rapamycin. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 65-69 21062901-7 2011 The differences between Tsc1(GFAP1)CKO and Tsc2(GFAP1)CKO mice were correlated with higher levels of mammalian target of rapamycin (mTOR) activation in Tsc2(GFAP1)CKO mice and were reversed by the mTOR inhibitor, rapamycin. Sirolimus 121-130 mechanistic target of rapamycin kinase Homo sapiens 132-136 21216928-1 2011 The identification of mammalian target of rapamycin (mTOR) as a major mediator of neurofibromatosis-1 (NF1) tumor growth has led to the initiation of clinical trials using rapamycin analogs. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 53-57 21162600-5 2011 De novo use of a mammalian target of rapamycin (mTOR) inhibitor (sirolimus or everolimus) or conversion from a calcineurin inhibitor to an mTOR inhibitor may constitute another therapeutic option to avoid or reduce calcineurin inhibitor-induced nephrotoxicity. Sirolimus 65-74 mechanistic target of rapamycin kinase Homo sapiens 17-46 21162600-5 2011 De novo use of a mammalian target of rapamycin (mTOR) inhibitor (sirolimus or everolimus) or conversion from a calcineurin inhibitor to an mTOR inhibitor may constitute another therapeutic option to avoid or reduce calcineurin inhibitor-induced nephrotoxicity. Sirolimus 65-74 mechanistic target of rapamycin kinase Homo sapiens 48-52 21268715-4 2011 Here we show that treating MCF7 breast cancer cells with rapamycin (an mTOR inhibitor) results in significant suppression of homologous recombination (HR) and nonhomologous end joining (NHEJ), two major mechanisms required for repairing ionizing radiation-induced DNA DSBs. Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 71-75 21073880-9 2011 This loop provides much of the surface buried at the protein-protein interface of the ternary complex, leading us to assert that preorganization upon rapamycin binding facilitates binding of the second molecule, mTOR. Sirolimus 150-159 mechanistic target of rapamycin kinase Homo sapiens 212-216 21208419-0 2011 The mTOR kinase inhibitor rapamycin decreases iNOS mRNA stability in astrocytes. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 4-8 21430336-7 2011 Notable examples include rapamycin (sirolimus) in suppressing the mTOR pathway associated hamartomas in dominantly inherited cancer family syndromes and angiotensin converting enzyme receptor blockers (ACE-RB) in preventing aortic dilatation in Marfan syndrome and related familial arteriopathies. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 66-70 21430336-7 2011 Notable examples include rapamycin (sirolimus) in suppressing the mTOR pathway associated hamartomas in dominantly inherited cancer family syndromes and angiotensin converting enzyme receptor blockers (ACE-RB) in preventing aortic dilatation in Marfan syndrome and related familial arteriopathies. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 66-70 20730884-1 2010 Sirolimus (Rapamune), a mammalian target of Rapamycin (mTOR) inhibitor, which has been used extensively in children following solid organ transplantation, has been demonstrated to have anti-angiogenic activity in pre-clinical models. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 24-53 21406469-6 2011 The common activation of the PI3K pathway in breast cancer has led to the development of compounds targeting the effector mechanisms of the pathway including selective and pan-PI3K/pan-AKT inhibitors, rapamycin analogs for mTOR inhibition, and TOR-catalytic subunit inhibitors. Sirolimus 201-210 mechanistic target of rapamycin kinase Homo sapiens 223-227 21915260-2 2011 METHODS: We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas. Sirolimus 115-124 mechanistic target of rapamycin kinase Homo sapiens 99-103 21079551-7 2010 The combination of sirolimus and leflunomide inhibited BK virus genome replication, large T antigen expression, PDK1, Akt, mammalian target of rapamycin, and p70S6K phosphorylation. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 123-152 20868675-10 2010 Rapamycin (pharmacological inhibitor of mTOR) resulted in decrease in prolidase activity. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 40-44 20730884-1 2010 Sirolimus (Rapamune), a mammalian target of Rapamycin (mTOR) inhibitor, which has been used extensively in children following solid organ transplantation, has been demonstrated to have anti-angiogenic activity in pre-clinical models. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 55-59 20937815-3 2010 Recently we found that rapamycin inhibits type I insulin-like growth factor (IGF-1)-stimulated lamellipodia formation and cell motility, indicating involvement of mTOR in regulating cell motility. Sirolimus 23-32 mechanistic target of rapamycin kinase Homo sapiens 163-167 21098662-8 2010 The remaining LTD was reduced by anisomycin, an inhibitor of protein synthesis, by U0126, an inhibitor of MEK1/2 kinases, and by rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), suggesting mediation by the same mechanisms as in WT. Sirolimus 129-138 mechanistic target of rapamycin kinase Homo sapiens 156-185 21098662-8 2010 The remaining LTD was reduced by anisomycin, an inhibitor of protein synthesis, by U0126, an inhibitor of MEK1/2 kinases, and by rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), suggesting mediation by the same mechanisms as in WT. Sirolimus 129-138 mechanistic target of rapamycin kinase Homo sapiens 187-191 20703217-1 2010 Sirolimus (SRL) is an antiproliferative agent inhibiting the mammalian target of rapamycin (mTOR) proposed as a non-nephrotoxic alternative to calcineurin inhibitors for the prevention of acute rejection in renal transplantation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 61-90 20926775-1 2010 Rapamycin, an inhibitor of the serine/threonine kinase mammalian target of rapamycin (mTOR), is a widely used immunosuppressive drug. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 55-84 20926775-1 2010 Rapamycin, an inhibitor of the serine/threonine kinase mammalian target of rapamycin (mTOR), is a widely used immunosuppressive drug. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 86-90 20854816-0 2010 mTOR inhibitor rapamycin suppresses striatal post-ischemic LTP. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 0-4 20854816-2 2010 To evaluate the involvement of mTOR complexes during ischemia we analyzed the time course of i-LTP by intracellular recordings of MSNs from corticostriatal slices incubated with 1muM mTOR inhibitor rapamycin. Sirolimus 198-207 mechanistic target of rapamycin kinase Homo sapiens 183-187 20861822-7 2010 A feature of increasing importance is that the mTOR pathway is central for vital aspects of tumor development, including angiogenesis and cell growth; rapamycin, therefore, has anticancer activities, which may prove critical in the fight against high cancer rates in transplant recipients. Sirolimus 151-160 mechanistic target of rapamycin kinase Homo sapiens 47-51 20861085-4 2010 Here, we show that the inactivation of mammalian target of rapamycin (mTor) by the mTor inhibitor rapamycin or knockdown of mTor reduced sphere formation and the expression of neural stem cell (NSC)/progenitor markers in CSLCs of the A172 glioblastoma cell line. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 70-74 20861085-4 2010 Here, we show that the inactivation of mammalian target of rapamycin (mTor) by the mTor inhibitor rapamycin or knockdown of mTor reduced sphere formation and the expression of neural stem cell (NSC)/progenitor markers in CSLCs of the A172 glioblastoma cell line. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 83-87 20861085-4 2010 Here, we show that the inactivation of mammalian target of rapamycin (mTor) by the mTor inhibitor rapamycin or knockdown of mTor reduced sphere formation and the expression of neural stem cell (NSC)/progenitor markers in CSLCs of the A172 glioblastoma cell line. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 83-87 21042741-4 2010 The well known mTOR inhibitor rapamycin has a disadvantage of feedback stimulation of Akt. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 15-19 21042741-8 2010 Our results indicated that anthocyanins significantly decreased phospho-mTOR comparable to rapamycin, a synthetic mTOR inhibitor, and this inhibitory effect of anthocyanins on mTOR was completely abrogated by inactivating AMPKalpha1. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 114-118 21042741-8 2010 Our results indicated that anthocyanins significantly decreased phospho-mTOR comparable to rapamycin, a synthetic mTOR inhibitor, and this inhibitory effect of anthocyanins on mTOR was completely abrogated by inactivating AMPKalpha1. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 114-118 21223797-4 2010 Treating HepG2 cells with rapamycin, a specific mTOR inhibitor, significantly reduced the survivin protein level but not affected the survivin transcription, indicating that tamoxifen and rapamycin were synergistic in regards to down-regulation of survivin expression in hepatocellular carcinoma cells. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 48-52 21223797-4 2010 Treating HepG2 cells with rapamycin, a specific mTOR inhibitor, significantly reduced the survivin protein level but not affected the survivin transcription, indicating that tamoxifen and rapamycin were synergistic in regards to down-regulation of survivin expression in hepatocellular carcinoma cells. Sirolimus 188-197 mechanistic target of rapamycin kinase Homo sapiens 48-52 21045832-1 2010 BACKGROUND: The combination of sorafenib (vascular endothelial growth factor receptor 2 inhibitor) and sirolimus (mammalian target of rapamycin inhibitor) might work synergistically. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 114-143 21228924-1 2010 The mammalian target of rapamycin (MTOR) assembles into two distinct complexes: mTOR complex 1 (mTORC1) is predominantly cytoplasmic and highly responsive to rapamycin, whereas mTOR complex 2 (mTORC2) is both cytoplasmic and nuclear, and relatively resistant to rapamycin. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 35-39 21228924-1 2010 The mammalian target of rapamycin (MTOR) assembles into two distinct complexes: mTOR complex 1 (mTORC1) is predominantly cytoplasmic and highly responsive to rapamycin, whereas mTOR complex 2 (mTORC2) is both cytoplasmic and nuclear, and relatively resistant to rapamycin. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 80-84 21228924-1 2010 The mammalian target of rapamycin (MTOR) assembles into two distinct complexes: mTOR complex 1 (mTORC1) is predominantly cytoplasmic and highly responsive to rapamycin, whereas mTOR complex 2 (mTORC2) is both cytoplasmic and nuclear, and relatively resistant to rapamycin. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 96-100 21228924-1 2010 The mammalian target of rapamycin (MTOR) assembles into two distinct complexes: mTOR complex 1 (mTORC1) is predominantly cytoplasmic and highly responsive to rapamycin, whereas mTOR complex 2 (mTORC2) is both cytoplasmic and nuclear, and relatively resistant to rapamycin. Sirolimus 158-167 mechanistic target of rapamycin kinase Homo sapiens 4-33 21228924-1 2010 The mammalian target of rapamycin (MTOR) assembles into two distinct complexes: mTOR complex 1 (mTORC1) is predominantly cytoplasmic and highly responsive to rapamycin, whereas mTOR complex 2 (mTORC2) is both cytoplasmic and nuclear, and relatively resistant to rapamycin. Sirolimus 158-167 mechanistic target of rapamycin kinase Homo sapiens 35-39 21228924-1 2010 The mammalian target of rapamycin (MTOR) assembles into two distinct complexes: mTOR complex 1 (mTORC1) is predominantly cytoplasmic and highly responsive to rapamycin, whereas mTOR complex 2 (mTORC2) is both cytoplasmic and nuclear, and relatively resistant to rapamycin. Sirolimus 158-167 mechanistic target of rapamycin kinase Homo sapiens 80-84 21228924-1 2010 The mammalian target of rapamycin (MTOR) assembles into two distinct complexes: mTOR complex 1 (mTORC1) is predominantly cytoplasmic and highly responsive to rapamycin, whereas mTOR complex 2 (mTORC2) is both cytoplasmic and nuclear, and relatively resistant to rapamycin. Sirolimus 158-167 mechanistic target of rapamycin kinase Homo sapiens 96-100 21040901-1 2010 Pten deficiency depletes hematopoietic stem cells (HSCs) but expands leukemia-initiating cells, and the mTOR inhibitor, rapamycin, blocks these effects. Sirolimus 120-129 mechanistic target of rapamycin kinase Homo sapiens 104-108 21182472-4 2010 Of note, rapamycin and FK506 bind to FKBP12, and the resulting complexes interfere with distinct intracellular signaling pathways driven, respectively, by the mammalian target of rapamycin and calcineurin phosphatase. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 159-188 20663789-3 2010 Recent reports suggest a possible beneficial role of the mTOR inhibitor rapamycin for TSC. Sirolimus 72-81 mechanistic target of rapamycin kinase Homo sapiens 57-61 20500493-1 2010 Immediate or early use of proliferation signal inhibitor (PSI)/mammalian target of rapamycin (mTOR) inhibitor therapy can avoid high exposure to calcineurin inhibitors but concerns exist relating to the risk of delayed graft function (DGF) and impaired wound healing with the mTOR sirolimus. Sirolimus 281-290 mechanistic target of rapamycin kinase Homo sapiens 63-92 20500493-1 2010 Immediate or early use of proliferation signal inhibitor (PSI)/mammalian target of rapamycin (mTOR) inhibitor therapy can avoid high exposure to calcineurin inhibitors but concerns exist relating to the risk of delayed graft function (DGF) and impaired wound healing with the mTOR sirolimus. Sirolimus 281-290 mechanistic target of rapamycin kinase Homo sapiens 94-98 21095445-4 2010 The trend has therefore been to use a low-dose CNI in combination with the mTOR-inhibitor sirolimus in order to reduce the risk of nephrotoxicity. Sirolimus 90-99 mechanistic target of rapamycin kinase Homo sapiens 75-79 21095447-4 2010 The first family of drugs that have these properties are mammalian target of rapamycin inhibitors: these include sirolimus and everolimus. Sirolimus 113-122 mechanistic target of rapamycin kinase Homo sapiens 57-86 21095452-2 2010 In animal models of experimental polycystic kidney disease, the mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus effectively reduce cyst growth and loss of renal function. Sirolimus 112-121 mechanistic target of rapamycin kinase Homo sapiens 64-93 21095452-2 2010 In animal models of experimental polycystic kidney disease, the mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus effectively reduce cyst growth and loss of renal function. Sirolimus 112-121 mechanistic target of rapamycin kinase Homo sapiens 95-99 20855840-1 2010 PURPOSE: Synergistic/additive cytotoxicity in tumor models and widespread applicability of fluoropyrimidines in solid tumors prompted the study of the combination of the mammalian target of rapamycin (mTOR) inhibitor, non-prodrug rapamycin analog ridaforolimus, with capecitabine. Sirolimus 190-199 mechanistic target of rapamycin kinase Homo sapiens 201-205 20703217-1 2010 Sirolimus (SRL) is an antiproliferative agent inhibiting the mammalian target of rapamycin (mTOR) proposed as a non-nephrotoxic alternative to calcineurin inhibitors for the prevention of acute rejection in renal transplantation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 92-96 21036716-2 2010 The aim of this study was to investigate the effects of the COX2 inhibitor celecoxib and the mTOR antagonist rapamycin on angiosarcoma cell lines. Sirolimus 109-118 mechanistic target of rapamycin kinase Homo sapiens 93-97 20600853-6 2010 The mTor inhibitor, rapamycin, activates autophagy, prevents PDE4A4 from forming intracellular aggregates and triggers the loss of bound p62 from PDE4A4. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 4-8 20842569-14 2010 Inhibitors of the mammalian target of rapamycin (i.e., sirolimus and everolimus) have not yet assumed a major place as adjunctive agents, as their safety and efficacy have not been well established in children. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 18-47 20429048-3 2010 The inhibitory effects of palmitate on the insulin signaling were diminished in PKCTheta- and mTOR (mammalian target of rapamycin)-deficient C2C12 myotubes, and C2C12 myotubes pre-treated with rapamycin. Sirolimus 120-129 mechanistic target of rapamycin kinase Homo sapiens 94-98 21495229-4 2010 Novel therapies, such as drugs that target cellular pathways, for example, mTOR inhibitor deforolimus, an analog of rapamycin, have been developed and used in clinical trials to treat women with progressive endometrial cancer. Sirolimus 116-125 mechanistic target of rapamycin kinase Homo sapiens 75-79 20664001-7 2010 It is noteworthy that the mammalian target of rapamycin (mTOR) inhibitor rapamycin also induced phosphorylation of eIF4E in a Mnk-dependent manner, whereas inhibition strongly enhanced its antileukemic effects. Sirolimus 46-55 mechanistic target of rapamycin kinase Homo sapiens 57-61 20811722-0 2010 Effect of rapamycin, an mTOR inhibitor, on radiation sensitivity of lung cancer cells having different p53 gene status. Sirolimus 10-19 mechanistic target of rapamycin kinase Homo sapiens 24-28 20686448-2 2010 Sirolimus, an inhibitor of the protein kinase mammalian target of rapamycin (mTOR) and a potent anti-proliferative agent, decreases cyst growth in several genetically distinct rodent models of polycystic kidney disease (PKD). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 46-75 20686448-2 2010 Sirolimus, an inhibitor of the protein kinase mammalian target of rapamycin (mTOR) and a potent anti-proliferative agent, decreases cyst growth in several genetically distinct rodent models of polycystic kidney disease (PKD). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 77-81 20599569-5 2010 Furthermore, the inhibition of mTOR by chronic infusion of rapamycin, a specific inhibitor of mTOR, into the ventricle retards the establishment of spatial learning. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 31-35 20599569-5 2010 Furthermore, the inhibition of mTOR by chronic infusion of rapamycin, a specific inhibitor of mTOR, into the ventricle retards the establishment of spatial learning. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 94-98 20566381-1 2010 Inhibition of mTOR by rapamycin has been shown to suppress seizures in TSC/PTEN genetic models. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 20970608-1 2010 BACKGROUND: The mammalian target of rapamycin inhibitors (mTORi) sirolimus (Si) and everolimus (Ev) induce pneumonitis, an unusual but potentially fatal adverse effect. Sirolimus 65-74 mechanistic target of rapamycin kinase Homo sapiens 16-45 21210335-6 2010 The use of mTOR inhibitors such as rapamycin and everolimus is discussed and recent clinical trials of these drugs in TSC are reviewed. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 11-15 20970608-1 2010 BACKGROUND: The mammalian target of rapamycin inhibitors (mTORi) sirolimus (Si) and everolimus (Ev) induce pneumonitis, an unusual but potentially fatal adverse effect. Sirolimus 76-78 mechanistic target of rapamycin kinase Homo sapiens 16-45 20629977-2 2010 Rapamycin (=sirolimus), a specific mTOR inhibitor, leads to G(1) arrest of many malignant cell lines and currently, analogues of rapamycin are being investigated as a cancer chemotherapeutic adjuvant. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 35-39 20668162-4 2010 Furthermore, the presumed role of mTOR in hypertrophy is derived from studies that used rapamycin to inhibit mTOR; yet, there is very little direct evidence that mTOR is the rapamycin-sensitive element that confers the hypertrophic response. Sirolimus 88-97 mechanistic target of rapamycin kinase Homo sapiens 109-113 20668162-4 2010 Furthermore, the presumed role of mTOR in hypertrophy is derived from studies that used rapamycin to inhibit mTOR; yet, there is very little direct evidence that mTOR is the rapamycin-sensitive element that confers the hypertrophic response. Sirolimus 88-97 mechanistic target of rapamycin kinase Homo sapiens 109-113 20668162-5 2010 In this study, we determined that, in skeletal muscle, overexpression of Rheb stimulates a PI3K/PKB-independent activation of mTOR signaling, and this is sufficient for the induction of a rapamycin-sensitive hypertrophic response. Sirolimus 188-197 mechanistic target of rapamycin kinase Homo sapiens 126-130 20629977-2 2010 Rapamycin (=sirolimus), a specific mTOR inhibitor, leads to G(1) arrest of many malignant cell lines and currently, analogues of rapamycin are being investigated as a cancer chemotherapeutic adjuvant. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 35-39 20629977-2 2010 Rapamycin (=sirolimus), a specific mTOR inhibitor, leads to G(1) arrest of many malignant cell lines and currently, analogues of rapamycin are being investigated as a cancer chemotherapeutic adjuvant. Sirolimus 129-138 mechanistic target of rapamycin kinase Homo sapiens 35-39 20368307-5 2010 Co-expression of mTOR significantly enhanced I(pi) in NaPi-IIa-expressing Xenopus oocytes, an effect abrogated by treatment with rapamycin (50 nM for the last 24 h of incubation). Sirolimus 129-138 mechanistic target of rapamycin kinase Homo sapiens 17-21 20716637-9 2010 Compared with single antibodies, the BIIB4 and BIIB5 combination also significantly further enhanced the antitumor activity of the epidermal growth factor receptor inhibitor erlotinib and the mTOR inhibitor rapamycin. Sirolimus 207-216 mechanistic target of rapamycin kinase Homo sapiens 192-196 20167228-6 2010 The DHEA-action was sensitive to the PI3K inhibitor LY294002 and the mammalian target of rapamycin (mTOR) inhibitor rapamycin. Sirolimus 89-98 mechanistic target of rapamycin kinase Homo sapiens 100-104 20581391-2 2010 The drug sirolimus suppresses mTOR signaling. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 30-34 21092676-0 2010 [Inhibition of cell growth by rapamycin through targeting mammalian target of rapamycin signaling pathway in nasopharyngeal carcinoma]. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 58-87 21092676-9 2010 RT-PCR showed that rapamycin significantly inhibited mRNA expression of mTOR in CNE-2 cells (t = 10.625, P < 0.01). Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 72-76 21092676-10 2010 CONCLUSIONS: Rapamycin inhibits the growth of CNE-1 and CNE-2 cells by inhibiting the progression of cell cycle, which could be achieved through decreasing the expression of mTOR. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 174-178 20505189-8 2010 Primary AML blasts without functional NF1, unlike blasts with functional NF1, displayed sensitivity to rapamycin-induced apoptosis, thus identifying a dependence on mammalian target of rapamycin (mTOR) signaling for survival. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 165-194 20505189-8 2010 Primary AML blasts without functional NF1, unlike blasts with functional NF1, displayed sensitivity to rapamycin-induced apoptosis, thus identifying a dependence on mammalian target of rapamycin (mTOR) signaling for survival. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 196-200 20626386-3 2010 We found that donor BALB/c bone marrow-derived DCs (BMDCs) pharmacologically modified by the mTOR inhibitor rapamycin had significantly enhanced ability to induce CD4(+)CD25(+)Foxp3(+) iTregs of recipient origin (C57BL/6 (B6)) in vitro under Treg driving conditions compared to unmodified BMDCs. Sirolimus 108-117 mechanistic target of rapamycin kinase Homo sapiens 93-97 20581056-7 2010 Tgs receiving rapamycin not only showed inhibition of the mTOR-associated downstream signaling but also displayed attenuated renal lesions. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 58-62 20569080-2 2010 AREAS COVERED IN THIS REVIEW: The analysis of molecular activity of the PI3K/AKT/mTOR pathway and resistance mechanisms of rapamycin and rapalogues led to the development of several inhibitory molecules. Sirolimus 123-132 mechanistic target of rapamycin kinase Homo sapiens 81-85 20506288-8 2010 RESULTS: Inhibition of mTOR by sirolimus or everolimus reduced synovial osteoclast formation and protected against local bone erosions and cartilage loss. Sirolimus 31-40 mechanistic target of rapamycin kinase Homo sapiens 23-27 20135346-3 2010 As mTOR inhibition by rapamycin is associated with attenuation of negative feedback to IRS-1, rapamycin is known to increase activation of AKT, which may reduce its anti-neoplastic activity. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 3-7 20483386-2 2010 The aim of this cohort study was to evaluate the effect of sirolimus as an mTOR inhibitor on hepatitis C recurrence in liver transplant recipients. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 75-79 19906497-11 2010 When ENZ was combined with the mTOR inhibitor, rapamycin, in H460 lung cancer cells, radiosensitization was observed. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 31-35 20585037-10 2010 The mTOR inhibitor rapamycin, but not AMD3100, inhibited growth of AML tumor xenografts. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 20071026-2 2010 We found that a combination of a farnesyltransferase inhibitor, tipifarnib, and an mTOR inhibitor, rapamycin, synergistically inhibited the growth of myeloid leukemia cell lines and primary leukemia cells by inducing apoptosis and cell-cycle blockage. Sirolimus 99-108 mechanistic target of rapamycin kinase Homo sapiens 83-87 20070623-2 2010 Recent reports suggest a possible beneficial role of the mTOR-inhibitor (mTOR-I) sirolimus for TSC; however, safety and efficiency of sirolimus in TSC patients after renal transplantation, both as primary immunosuppressant as well as anti-proliferative agent, are still undefined. Sirolimus 81-90 mechanistic target of rapamycin kinase Homo sapiens 73-77 20439463-4 2010 mTOR inhibitor rapamycin or NS5A knockdown blocked S6K1 and 4EBP1 phosphorylation increase in NS5A-Huh7 and HCV replicon cells, suggesting that NS5A specifically regulated mTOR activation. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 0-4 20439463-4 2010 mTOR inhibitor rapamycin or NS5A knockdown blocked S6K1 and 4EBP1 phosphorylation increase in NS5A-Huh7 and HCV replicon cells, suggesting that NS5A specifically regulated mTOR activation. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 172-176 20439463-7 2010 Moreover, NS5A suppressed caspase 3 and poly(ADP-ribose) polymerase activation, which was abolished by NS5A knockdown or rapamycin, indicating NS5A inhibited apoptosis specifically through the mTOR pathway. Sirolimus 121-130 mechanistic target of rapamycin kinase Homo sapiens 193-197 20382746-7 2010 The mammalian target of rapamycin (mTOR)/S6 kinase 1 (S6K1) inhibition with rapamycin inhibited IFN- and EGF-induced protein synthesis, suggesting that IFN-induced protein synthesis is modulated by mTOR/S6K1 activation. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 35-39 20382746-7 2010 The mammalian target of rapamycin (mTOR)/S6 kinase 1 (S6K1) inhibition with rapamycin inhibited IFN- and EGF-induced protein synthesis, suggesting that IFN-induced protein synthesis is modulated by mTOR/S6K1 activation. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 198-202 20642692-1 2010 Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease, and sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to significantly retard cyst expansion in animal models. Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 114-143 20642692-1 2010 Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease, and sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to significantly retard cyst expansion in animal models. Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 145-149 20642692-8 2010 While sirolimus treatment reduced the activation of mTOR in peripheral blood mononuclear cells, it failed to prevent mTOR activation in kidney tubular cells, this could account for the inefficiency of treatment on cyst growth. Sirolimus 6-15 mechanistic target of rapamycin kinase Homo sapiens 52-56 20642692-9 2010 Together, our results suggest that the dose of sirolimus required to inhibit mTOR varies according to the tissue. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 77-81 20597028-4 2010 The efficacy of derivatives of the natural product rapamycin (sirolimus), which functions as an allosteric inhibitor of mTORC1, has validated mTOR inhibition as an anticancer treatment. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 120-124 20603607-3 2010 In particular, kainate-induced status epilepticus causes abnormal activation of the mTOR pathway, and the mTOR inhibitor, rapamycin, can decrease the development of neuronal death and chronic seizures in the kainate model. Sirolimus 122-131 mechanistic target of rapamycin kinase Homo sapiens 106-110 20421347-3 2010 We report a previously unsuspected role for the nonprotein-coding RNA GAS5 in the inhibition of T-cell proliferation produced by mTOR antagonists such as rapamycin. Sirolimus 154-163 mechanistic target of rapamycin kinase Homo sapiens 129-133 20177775-0 2010 Effect of combination treatment of rapamycin and isoflavones on mTOR pathway in human glioblastoma (U87) cells. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 64-68 20177775-5 2010 Rapamycin and its analogues are known to inhibit mTOR pathway; however, they also show simultaneous upregulation of Akt and eIF4E survival pathways on inhibition of mTOR, rendering cells more resistant to rapamycin treatment. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 49-53 20177775-5 2010 Rapamycin and its analogues are known to inhibit mTOR pathway; however, they also show simultaneous upregulation of Akt and eIF4E survival pathways on inhibition of mTOR, rendering cells more resistant to rapamycin treatment. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 165-169 20177775-5 2010 Rapamycin and its analogues are known to inhibit mTOR pathway; however, they also show simultaneous upregulation of Akt and eIF4E survival pathways on inhibition of mTOR, rendering cells more resistant to rapamycin treatment. Sirolimus 205-214 mechanistic target of rapamycin kinase Homo sapiens 165-169 20177775-6 2010 In this study we investigated the effect of combination treatment of rapamycin with isoflavones such as genistein and biochanin A on mTOR pathway and activation of Akt and eIF4E in human glioblastoma (U87) cells. Sirolimus 69-78 mechanistic target of rapamycin kinase Homo sapiens 133-137 20643380-3 2010 Molecularly-targeted treatments using mTOR inhibitors (such as rapamycin) are showing great promise for the physical and neurological phenotype of TSC. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 38-42 20108343-4 2010 In an attempt to avoid bilateral nephrectomies, the patient was treated with the mTOR inhibitor sirolimus. Sirolimus 96-105 mechanistic target of rapamycin kinase Homo sapiens 81-85 20630348-5 2010 The involvement of mTOR in LAM pathogenesis is the basis for initiation of therapeutic trials of mTOR inhibitors (e.g., sirolimus). Sirolimus 120-129 mechanistic target of rapamycin kinase Homo sapiens 19-23 20630348-5 2010 The involvement of mTOR in LAM pathogenesis is the basis for initiation of therapeutic trials of mTOR inhibitors (e.g., sirolimus). Sirolimus 120-129 mechanistic target of rapamycin kinase Homo sapiens 97-101 21188109-1 2010 Patients with mantle cell lymphoma (MCL) have a poor prognosis; consequently, new therapeutic approaches, such as rapamycin and its derivates, mammalian target of rapamycin (mTOR) inhibitors, are warranted. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 143-172 21188109-1 2010 Patients with mantle cell lymphoma (MCL) have a poor prognosis; consequently, new therapeutic approaches, such as rapamycin and its derivates, mammalian target of rapamycin (mTOR) inhibitors, are warranted. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 174-178 20603607-4 2010 Here, we discuss the significance of these findings and extend them further by identifying upstream signaling pathways through which kainate status epilepticus activates the mTOR pathway and by demonstrating limited situations where rapamycin may paradoxically increase mTOR activation and worsen neuronal death in the kainate model. Sirolimus 233-242 mechanistic target of rapamycin kinase Homo sapiens 270-274 20360610-10 2010 Mammalian target of rapamycin (mTOR) phosphorylation was increased in G391R cells with increased survival (55%) compared with WT (30%) and had increased sensitivity to rapamycin. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 31-35 20395440-5 2010 In addition, mTOR inhibition via rapamycin administration reduced cell proliferation in UCC cell lines RT4, T24, J82, and UMUC3 in a dose-dependent manner to 6% of control levels and was significant at 1 nmol/L in J82, T24, and RT4 cells (P < 0.01, P < 0.01, P = 0.03, respectively) and at 10 nmol/L in UMUC3 cells (P = 0.03). Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 13-17 20606252-7 2010 In these senescence-prone cells, the mTOR inhibitor rapamycin converted nutlin-3a-induced senescence into quiescence. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 37-41 20299603-8 2010 We have demonstrated that exposure of HIMEC to low levels of irradiation induced Akt and mTOR phosphorylation, which was attenuated by curcumin, rapamycin, LY294002, and mTOR small interference RNA (siRNA). Sirolimus 145-154 mechanistic target of rapamycin kinase Homo sapiens 89-93 20299475-2 2010 Whereas acute treatment of insulin target cells with the mTOR complex 1 (mTORC1) inhibitor rapamycin prevents nutrient-induced insulin resistance, the chronic effect of rapamycin on insulin sensitivity and glucose metabolism in vivo remains elusive. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 57-61 20833335-5 2010 The pathogenesis of these familial syndromes is linked by the shared regulation of a common pathway, the protein kinase mammalian target of rapamycin (mTOR). Sirolimus 140-149 mechanistic target of rapamycin kinase Homo sapiens 151-155 20497911-8 2010 Inhibitors of mTOR (sirolimus, temsirolimus) demonstrated an antitumoral activity in the PEComas. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 14-18 20368736-6 2010 We also found that p53 knockdown or inhibition of mTOR activity by rapamycin cotreatment impairs 6-TG- and 5-FU-induced upregulation of BNIP3 protein levels and autophagy. Sirolimus 67-76 mechanistic target of rapamycin kinase Homo sapiens 50-54 20496258-2 2010 The discovery of the involvement of rapamycin-insensitive mTOR complex 2 (mTORC2) in the activation of Akt, combined with the limited clinical antitumor activity of mTOR complex 1 (mTORC1)-directed rapamycin analogs, have led to the discovery of ATP-competitive selective inhibitors of the mTOR kinase that inhibit the function of both mTORC1 and mTORC2. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 74-78 20496258-2 2010 The discovery of the involvement of rapamycin-insensitive mTOR complex 2 (mTORC2) in the activation of Akt, combined with the limited clinical antitumor activity of mTOR complex 1 (mTORC1)-directed rapamycin analogs, have led to the discovery of ATP-competitive selective inhibitors of the mTOR kinase that inhibit the function of both mTORC1 and mTORC2. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 74-78 20351317-13 2010 Furthermore, LH-directed changes in AMPK and GSK3B phosphorylation appear to exert a greater impact on progesterone synthesis in the corpus luteum than rapamycin-sensitive MTOR-mediated events. Sirolimus 152-161 mechanistic target of rapamycin kinase Homo sapiens 172-176 20230819-5 2010 Inhibition of PI3K or mTOR/p70S6K by wortmannin and rapamycin, respectively, increased apoptosis and inhibited phosphorylation of Akt and p70S6K induced by single-dose oxidative stress. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 22-26 19856312-2 2010 In this study, to elucidate whether the rapamycin, the inhibitor of the mTOR (mammalian target of rapamaycin), can enhance the potentiation of TXT and 5-fluorouracil (5-Fu) in gastric carcinoma cells. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 72-76 19856312-2 2010 In this study, to elucidate whether the rapamycin, the inhibitor of the mTOR (mammalian target of rapamaycin), can enhance the potentiation of TXT and 5-fluorouracil (5-Fu) in gastric carcinoma cells. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 78-108 20375166-11 2010 The mTOR inhibitor rapamycin reversed the inhibitory effects of SOCS3. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 20472200-3 2010 The patient received the mammalian target of rapamycin inhibitor, sirolimus, for recurrent subependymal giant cell brain tumors. Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 25-54 20144629-2 2010 IGF-I-induced IGF-I receptor decrease was abolished by LY294002 (phosphoinositide 3-kinase inhibitor) and partially attenuated by rapamycin (an inhibitor of mammalian target of rapamycin [mTOR]). Sirolimus 130-139 mechanistic target of rapamycin kinase Homo sapiens 157-186 20144629-2 2010 IGF-I-induced IGF-I receptor decrease was abolished by LY294002 (phosphoinositide 3-kinase inhibitor) and partially attenuated by rapamycin (an inhibitor of mammalian target of rapamycin [mTOR]). Sirolimus 130-139 mechanistic target of rapamycin kinase Homo sapiens 188-192 20459775-4 2010 Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. Sirolimus 76-85 mechanistic target of rapamycin kinase Homo sapiens 61-65 20127734-12 2010 Attenuation of Rheb expression or treatment with the mTOR inhibitor rapamycin decreased proliferation of PC3 and DU145 cells, with a decrease in the activated form of p70S6 kinase, one of the main targets of mTOR. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 53-57 20127734-12 2010 Attenuation of Rheb expression or treatment with the mTOR inhibitor rapamycin decreased proliferation of PC3 and DU145 cells, with a decrease in the activated form of p70S6 kinase, one of the main targets of mTOR. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 208-212 20102553-2 2010 The mammalian target of rapamycin inhibitors (mTORi), sirolimus and everolimus, have been demonstrated to attenuate the progression of CAV and are cytotoxic to EPC. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 4-33 20457898-8 2010 Like rapamycin, which is known to suppress senescence, p53 inhibited the mTOR pathway. Sirolimus 5-14 mechanistic target of rapamycin kinase Homo sapiens 73-77 20495773-8 2010 The mTOR signaling cascade has been implicated in membrane traffic and is activated in nearly all human cancers, but clinical response to the mTOR-specific inhibitor rapamycin has been disappointing. Sirolimus 166-175 mechanistic target of rapamycin kinase Homo sapiens 4-8 20495773-8 2010 The mTOR signaling cascade has been implicated in membrane traffic and is activated in nearly all human cancers, but clinical response to the mTOR-specific inhibitor rapamycin has been disappointing. Sirolimus 166-175 mechanistic target of rapamycin kinase Homo sapiens 142-146 20459645-9 2010 The study suggests that inhibition of mTOR by rapamycin augments whereas overexpression of mTOR/p70S6 kinase inhibits OPN-induced ICAM-1 expression. Sirolimus 46-55 mechanistic target of rapamycin kinase Homo sapiens 38-42 20445056-4 2010 To this end, we show that the in vivo infusion of the mTOR inhibitor rapamycin led to a significant attenuation of the phase-delaying effect of early-night light. Sirolimus 69-78 mechanistic target of rapamycin kinase Homo sapiens 54-58 20139176-5 2010 The activation of HIF-1alpha by TNFalpha/IL-4 was countered by the phosphoinositol 3-kinase (PI3K) inhibitor LY-294002 and rapamycin, an antagonist of mammalian target of rapamycin (mTOR), but not by inhibition of the MAPK pathway. Sirolimus 123-132 mechanistic target of rapamycin kinase Homo sapiens 151-180 20139176-5 2010 The activation of HIF-1alpha by TNFalpha/IL-4 was countered by the phosphoinositol 3-kinase (PI3K) inhibitor LY-294002 and rapamycin, an antagonist of mammalian target of rapamycin (mTOR), but not by inhibition of the MAPK pathway. Sirolimus 123-132 mechanistic target of rapamycin kinase Homo sapiens 182-186 20420793-6 2010 Everolimus is derived from the mTOR inhibitor sirolimus and is in Phase III study. Sirolimus 46-55 mechanistic target of rapamycin kinase Homo sapiens 31-35 20178983-6 2010 Using an animal model of AD, we show that pharmacologically restoring mTOR signaling with rapamycin rescues cognitive deficits and ameliorates Abeta and Tau pathology by increasing autophagy. Sirolimus 90-99 mechanistic target of rapamycin kinase Homo sapiens 70-74 19853261-3 2010 Sirolimus is a well-established inhibitor of the mammalian target of rapamycin. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 49-78 19853261-12 2010 CONCLUSIONS: Sirolimus appears to enhance the cytotoxicity of cisplatin in malignant pleural mesothelioma cell lines through the mammalian target of rapamycin pathway. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 129-158 19931998-10 2010 Treating HepG2 cells with rapamycin, a specific mTOR inhibitor, significantly reduce survivin protein level but did not affect survivin transcription, which indicated that tamoxifen and rapamycin were synergistic in regards to down-regulation of survivin expression in hepatocellular carcinoma cells. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 48-52 20133820-7 2010 ANXA1, GPNMB, LTF, RND3, S100A11, SFRP4, and NPTX1 genes were likely to be mTOR effector genes in SEGA, as their expression was modulated by an mTOR inhibitor, rapamycin, in SEGA-derived cells. Sirolimus 160-169 mechanistic target of rapamycin kinase Homo sapiens 75-79 20133820-7 2010 ANXA1, GPNMB, LTF, RND3, S100A11, SFRP4, and NPTX1 genes were likely to be mTOR effector genes in SEGA, as their expression was modulated by an mTOR inhibitor, rapamycin, in SEGA-derived cells. Sirolimus 160-169 mechanistic target of rapamycin kinase Homo sapiens 144-148 19931998-10 2010 Treating HepG2 cells with rapamycin, a specific mTOR inhibitor, significantly reduce survivin protein level but did not affect survivin transcription, which indicated that tamoxifen and rapamycin were synergistic in regards to down-regulation of survivin expression in hepatocellular carcinoma cells. Sirolimus 186-195 mechanistic target of rapamycin kinase Homo sapiens 48-52 20116405-1 2010 Inhibition of mTORC1 with the mTOR inhibitor rapamycin may lead to an induction of Akt phosphorylation in cancer cells via mTORC2 activation. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 14-18 20372065-3 2010 It was reported recently that rapamycin is able to extend the lifespan of a mammal--implicating the mammalian TOR (mTOR). Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 115-119 20704577-5 2010 PBTDs possessed inhibitory activity against mTOR and also impeded hyper-phosphorylation of Akt as a feedback of inhibition of mTOR by rapamycin. Sirolimus 134-143 mechanistic target of rapamycin kinase Homo sapiens 126-130 20102778-6 2010 mTOR-specific siRNA effectively suppressed HeLa cell growth through mechanisms including inhibition of the cell cycle and increased apoptosis, which were similar to the mechanisms of rapamycin action. Sirolimus 183-192 mechanistic target of rapamycin kinase Homo sapiens 0-4 20099302-10 2010 Rapamycin, an inhibitor of mTOR, is known to induce autophagy. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 20099302-11 2010 Serotonin could override rapamycin by an mTOR-independent pathway and activate common downstream signals such as p70S6K and 4E-BP1. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 41-45 20130026-2 2010 Calcineurin inhibitors and sirolimus (mTOR inhibitor), commonly used in transplant patients as immunosuppressives, have antifungal activity. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 38-42 20492406-8 2010 Based on the evidence that downregulation of the mTOR pathway due to treatment with rapamycin (everolimus) would suppress tumor cell growth, an experimental study using the GCT cell line was designed to clarify whether HIF-1alpha and VEGF expressions decline. Sirolimus 84-93 mechanistic target of rapamycin kinase Homo sapiens 49-53 20371718-1 2010 The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway mediates multiple myeloma (MM) cell proliferation, survival, and development of drug resistance, underscoring the role of mTOR inhibitors, such as rapamycin, with potential anti-MM activity. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 72-76 20371718-1 2010 The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway mediates multiple myeloma (MM) cell proliferation, survival, and development of drug resistance, underscoring the role of mTOR inhibitors, such as rapamycin, with potential anti-MM activity. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 208-212 20371718-3 2010 We confirmed that suppression of mTOR signaling in MM cells by rapamycin was associated with upregulation of Akt phosphorylation. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 33-37 20371718-10 2010 Our data suggest that mutual suppression of the PI3K/Akt/mTOR pathway by rapamycin and perifosine combination induces synergistic MM cell cytotoxicity, providing the rationale for clinical trials in patients with relapsed/refractory MM. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 57-61 20106729-4 2010 VEGF(165) was constantly secreted by all cultured tumor cells in an mTOR-dependent manner, as it was inhibited by the mTOR inhibitor rapamycin. Sirolimus 133-142 mechanistic target of rapamycin kinase Homo sapiens 68-72 20106729-4 2010 VEGF(165) was constantly secreted by all cultured tumor cells in an mTOR-dependent manner, as it was inhibited by the mTOR inhibitor rapamycin. Sirolimus 133-142 mechanistic target of rapamycin kinase Homo sapiens 118-122 20234352-4 2010 First-generation mTOR inhibitors are sirolimus derivatives (rapalogs), which have been evaluated extensively in cancer patients. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 17-21 19642865-0 2010 Rapamycin promotes the osteoblastic differentiation of human embryonic stem cells by blocking the mTOR pathway and stimulating the BMP/Smad pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 98-102 19642865-4 2010 Under feeder-free culture conditions, rapamycin (an mTOR inhibitor) potently inhibited the activities of mTOR and p70S6K in undifferentiated hESCs; however, LY294002 (a PI3K inhibitor) and an AKT inhibitor had no effects. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 52-56 19642865-4 2010 Under feeder-free culture conditions, rapamycin (an mTOR inhibitor) potently inhibited the activities of mTOR and p70S6K in undifferentiated hESCs; however, LY294002 (a PI3K inhibitor) and an AKT inhibitor had no effects. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 105-109 20459645-14 2010 Inhibition of mTOR by rapamycin attenuates Ser-371 phosphorylation but does not have any effect on Thr-389 and Thr-421/Ser-424 phosphorylation of p70S6 kinase. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 19966866-4 2010 Tsc1-Kras(G12D) tumors showed consistent activation of mTOR (mammalian target of rapamycin)C1 and responded to treatment with rapamycin, leading to significantly improved survival, whereas rapamycin had minor effects on cancers in Kras(G12D) alone mice. Sirolimus 81-90 mechanistic target of rapamycin kinase Homo sapiens 55-59 20022946-1 2010 The mammalian target of rapamycin (mTOR) Ser/Thr kinase signals in at least two multiprotein complexes distinguished by their different partners and sensitivities to rapamycin. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 35-39 20022946-4 2010 Before the identification of distinct mTOR complexes, mTOR was reported to autophosphorylate on Ser-2481 in vivo in a rapamycin- and amino acid-insensitive manner. Sirolimus 118-127 mechanistic target of rapamycin kinase Homo sapiens 54-58 20142330-7 2010 Lastly, the finding that endometrial cancer cell lines were especially sensitive to the mTOR (mammalian target of rapamycin) inhibitor rapamycin prompted us to test its efficacy against Lkb1-driven endometrial cancers. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 88-92 20072130-2 2010 The mTOR kinase functions in two complexes, TORC1 (target of rapamycin complex-1) and TORC2 (target of rapamycin complex-2); however, neither of these complexes is fully inhibited by the allosteric inhibitor rapamycin or its analogs. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 4-8 20350481-7 2010 Thus mTOR offers a window into diverse facets of lupus pathogenesis as well as a unifying narrative in our understanding of the therapeutic efficacy of rapamycin in SLE. Sirolimus 152-161 mechanistic target of rapamycin kinase Homo sapiens 5-9 19688827-7 2010 Treatment with rapamycin and paclitaxel resulted in decreased phosphorylation of S6 and 4E-BP1, two critical downstream targets of the mTOR pathway. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 135-139 20075061-2 2010 mTOR inhibitors, such as rapamycin, are highly effective in several rodent models of PKD, but these models result from mutations in genes other than Pkd1 and Pkd2, which are the primary genes responsible for human autosomal dominant PKD. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 0-4 20155724-2 2010 Its blockade, by mTOR inhibitors (mTOR-Is), such as sirolimus or everolimus, leads to antiproliferative effects. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 17-21 20155724-2 2010 Its blockade, by mTOR inhibitors (mTOR-Is), such as sirolimus or everolimus, leads to antiproliferative effects. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 34-38 19935717-7 2010 Sorafenib induces reciprocal upregulation of Akt phosphorylation; and simultaneous inhibition of downstream mTOR with rapamycin leads to synergistic effects. Sirolimus 118-127 mechanistic target of rapamycin kinase Homo sapiens 108-112 20048174-3 2010 On this mechanistic basis, we treated three consecutive patients with metastatic PEComa with an oral mTOR inhibitor, sirolimus. Sirolimus 117-126 mechanistic target of rapamycin kinase Homo sapiens 101-105 20014960-4 2010 The mammalian target of rapamycin, which is a sensor of the mitochondrial transmembrane potential, has been successfully targeted for treatment of SLE with rapamycin or sirolimus in both patients and animal models. Sirolimus 169-178 mechanistic target of rapamycin kinase Homo sapiens 4-33 20193134-4 2010 Moreover, inhibition of mTOR activity by rapamycin resulted in a reduction of SREBP-1c protein expression and adipogenesis in cells. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 24-28 20022946-10 2010 These data suggest that mTORC1- and likely mTORC2-associated mTOR Ser-2481 autophosphorylation directly monitors intrinsic mTORC-specific catalytic activity and reveal that rapamycin inhibits mTORC1 signaling in vivo by reducing mTORC1 catalytic activity. Sirolimus 173-182 mechanistic target of rapamycin kinase Homo sapiens 24-28 20048174-0 2010 Clinical activity of mTOR inhibition with sirolimus in malignant perivascular epithelioid cell tumors: targeting the pathogenic activation of mTORC1 in tumors. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 21-25 19815051-0 2010 The rapamycin-derivative RAD001 (everolimus) inhibits cell viability and interacts with the Akt-mTOR-p70S6K pathway in human medullary thyroid carcinoma cells. Sirolimus 4-13 mechanistic target of rapamycin kinase Homo sapiens 96-100 19914305-11 2010 These results, taken together, indicate that Bim protein is the key mediator of apoptosis induced by Dex and also responsible for the potentiating effect of rapamycin, providing molecular criteria for the use of glucocorticoids combined with mTOR inhibitors in myeloma therapy. Sirolimus 157-166 mechanistic target of rapamycin kinase Homo sapiens 242-246 20089925-1 2010 We report that rapamycin, an allosteric inhibitor of certain but not all actions of the key cellular kinase mammalian target of rapamycin (mTOR), protects neurons from death in both cellular and animal toxin models of Parkinson"s disease (PD). Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 108-137 19906641-11 2010 In addition, RvE1 enhanced phagocytosis of zymosan A by human macrophages, which are inhibited by PD98059 and rapamycin (mTOR inhibitor). Sirolimus 110-119 mechanistic target of rapamycin kinase Homo sapiens 121-125 20089925-1 2010 We report that rapamycin, an allosteric inhibitor of certain but not all actions of the key cellular kinase mammalian target of rapamycin (mTOR), protects neurons from death in both cellular and animal toxin models of Parkinson"s disease (PD). Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 139-143 19945507-6 2010 Only TS but not an equally antiprion active PKC inhibitor could be partially antagonized by substochiometric 1 nM rapamycin suggesting that there are pathways via mammalian target of rapamycin (mTOR) that interfere with tocopherol"s biological effects. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 163-192 20089925-4 2010 The capacity of rapamycin to provide neuroprotection in PD models appears to arise from its selective suppression of some but not all actions of mTOR, as indicated by the contrasting finding that Torin1, a full catalytic mTOR inhibitor, is not protective and induces Akt dephosphorylation and neuron death. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 145-149 19945507-6 2010 Only TS but not an equally antiprion active PKC inhibitor could be partially antagonized by substochiometric 1 nM rapamycin suggesting that there are pathways via mammalian target of rapamycin (mTOR) that interfere with tocopherol"s biological effects. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 194-198 20089925-4 2010 The capacity of rapamycin to provide neuroprotection in PD models appears to arise from its selective suppression of some but not all actions of mTOR, as indicated by the contrasting finding that Torin1, a full catalytic mTOR inhibitor, is not protective and induces Akt dephosphorylation and neuron death. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 221-225 20068177-2 2010 Rapamycin and its analogues (rapalogs) partially inhibit mTOR through allosteric binding to mTOR complex 1 (mTORC1) but not mTOR complex 2 (mTORC2), an emerging player in cancer. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 57-61 19634141-6 2010 We demonstrate that rapamycin significantly inhibited human NF1-MPNST mTOR pathway activation and explant growth in vivo at doses as low as 1.0 mg/kg/day, without systemic toxicities. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 70-74 19634141-8 2010 Rapamycin effectively decreased activation of S6 downstream of mTOR, but there was accompanied increased Akt activation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 63-67 20068177-2 2010 Rapamycin and its analogues (rapalogs) partially inhibit mTOR through allosteric binding to mTOR complex 1 (mTORC1) but not mTOR complex 2 (mTORC2), an emerging player in cancer. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 92-96 20068177-2 2010 Rapamycin and its analogues (rapalogs) partially inhibit mTOR through allosteric binding to mTOR complex 1 (mTORC1) but not mTOR complex 2 (mTORC2), an emerging player in cancer. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 92-96 20203370-6 2010 In the androgen responsive prostate cancer cell line LNCaP, androgen and the mTOR inhibitor rapamycin synergistically activated androgen target genes. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 77-81 19917848-5 2010 TSC2 and PTEN are two key inhibitors of the Akt/mammalian target of rapamycin (mTOR) pathway and the specific inhibition of mTOR with rapamycin or RAD001 inhibited cell proliferation of PET cell lines. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 79-83 20146692-6 2010 Antagonism of the mTOR pathway with rapamycin and related compounds may provide new therapeutic options for TSC patients. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 18-22 20019183-6 2010 Rapamycin inhibited S6K at mTOR-sensitive phosphorylation sites in response to strain and hypoxia. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 19919613-1 2010 Sirolimus is one treatment option in transplant recipients with Kaposi"s sarcoma (KS), which involves dysregulation of Akt-mammalian target of rapamycin (mTOR) signaling pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 119-152 19919613-1 2010 Sirolimus is one treatment option in transplant recipients with Kaposi"s sarcoma (KS), which involves dysregulation of Akt-mammalian target of rapamycin (mTOR) signaling pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 154-158 19919613-12 2010 Suppressed expression of VEGF, p-Akt, and p-mTOR was the major event of signaling modification through the long-term use of sirolimus. Sirolimus 124-133 mechanistic target of rapamycin kinase Homo sapiens 44-48 20549474-8 2010 These inhibitors bind to the ATP binding site of the kinase domain of mTOR and as a result inhibit both mTOR complexes, TORC1 (rapamycin sensitive) and TORC2 (rapamycin resistant). Sirolimus 127-136 mechanistic target of rapamycin kinase Homo sapiens 70-74 20047144-5 2010 More recently, rapamycin (sirolimus) analogs that antagonize the mTOR signaling pathway have been approved for the treatment of several cancers. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 65-69 20047144-5 2010 More recently, rapamycin (sirolimus) analogs that antagonize the mTOR signaling pathway have been approved for the treatment of several cancers. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 65-69 20549474-8 2010 These inhibitors bind to the ATP binding site of the kinase domain of mTOR and as a result inhibit both mTOR complexes, TORC1 (rapamycin sensitive) and TORC2 (rapamycin resistant). Sirolimus 127-136 mechanistic target of rapamycin kinase Homo sapiens 104-108 19887566-7 2010 Insulin phosphorylation of S6K1 correlated with IRS-1 ser1101 phosphorylation and the mTOR-S6K1 pathway inhibitor rapamycin prevented IRS-1 serine phosphorylation. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 86-90 20043723-10 2010 Finally, increased knowledge of molecular and cellular mechanisms involved with NF1 tumorigenesis has led to multiple preclinical and clinical studies of targeted therapy, including the mTOR inhibitor rapamycin, which is demonstrating promising preclinical results for treatment of MPNSTs and gliomas. Sirolimus 201-210 mechanistic target of rapamycin kinase Homo sapiens 186-190 19661225-7 2010 In contrast, rapamycin-induced inhibition of mTOR did not significantly affect cell proliferation because it simultaneously stimulated PI3K/Akt activation and cyclin D1 expression. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 45-49 19562254-1 2010 We evaluated the anti-tumor activity and safety of erlotinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor, plus sirolimus, an inhibitor of the mammalian target of rapamycin, among patients with recurrent glioblastoma (GBM) in a phase 2, open-label, single-arm trial. Sirolimus 145-154 mechanistic target of rapamycin kinase Homo sapiens 176-205 19845851-0 2010 Rapamycin and CCI-779 inhibit the mammalian target of rapamycin signalling in hepatocellular carcinoma. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 34-63 19845851-10 2010 Upon rapamycin and CCI-779 treatment, the phosphorylation level of mTOR and p70S6K in HCC cell lines was significantly reduced, indicating that both drugs can suppress mTOR activity in HCC cells. Sirolimus 5-14 mechanistic target of rapamycin kinase Homo sapiens 67-71 19845851-10 2010 Upon rapamycin and CCI-779 treatment, the phosphorylation level of mTOR and p70S6K in HCC cell lines was significantly reduced, indicating that both drugs can suppress mTOR activity in HCC cells. Sirolimus 5-14 mechanistic target of rapamycin kinase Homo sapiens 168-172 20013687-5 2009 This overview provides an insight into the disease and the specific mTOR inhibitor sirolimus, which is currently tested in clinical trials. Sirolimus 83-92 mechanistic target of rapamycin kinase Homo sapiens 68-72 20072839-1 2010 Temsirolimus, an ester of sirolimus (rapamycin), selectively inhibits the kinase mammalian target of rapamycin and consequently blocks the translation of cell cycle regulatory proteins and prevents overexpression of angiogenic growth factors. Sirolimus 3-12 mechanistic target of rapamycin kinase Homo sapiens 81-110 20072839-1 2010 Temsirolimus, an ester of sirolimus (rapamycin), selectively inhibits the kinase mammalian target of rapamycin and consequently blocks the translation of cell cycle regulatory proteins and prevents overexpression of angiogenic growth factors. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 81-110 19800362-4 2010 Previously, the inhibitors, rapamycin for mTOR, wortmannin for phosphoinositide 3 kinase (PI3K) and PD98059 for ERK, each blocked the upregulation of the System A transporter in IAA depleted APC neurons. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 42-46 19944562-7 2010 Hopes are high for mTor inhibitors (sirolimus and everolimus) and treatment trials are currently underway. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 19-23 20080789-6 2009 Inhibition of mTOR not only enhances aerobic glycolysis, but also induces a state of increased dependence on aerobic glycolysis in leukemic cells, as shown by the synergy between the glycolytic inhibitor 2-deoxyglucose and rapamycin in decreasing cell viability. Sirolimus 223-232 mechanistic target of rapamycin kinase Homo sapiens 14-18 19875810-4 2009 Inhibition of mTOR with rapamycin delays recovery of renal function after acute kidney injury. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 14-18 19920197-7 2009 These results thus suggest that perifosine inhibits the mTOR axis through a different mechanism from inhibition of mTOR signaling by classic mTOR inhibitors such as rapamycin. Sirolimus 165-174 mechanistic target of rapamycin kinase Homo sapiens 115-119 19920197-7 2009 These results thus suggest that perifosine inhibits the mTOR axis through a different mechanism from inhibition of mTOR signaling by classic mTOR inhibitors such as rapamycin. Sirolimus 165-174 mechanistic target of rapamycin kinase Homo sapiens 115-119 19923913-5 2009 Selective inhibition of the PI3K-AKT-mTOR pathway using pharmacologic inhibitors (LY294002, AKT inhibitor VIII, Rapamycin) significantly attenuated expression of p-AKT and p-70S6K, respectively and radiosensitized SKBR3 cells. Sirolimus 112-121 mechanistic target of rapamycin kinase Homo sapiens 37-41 19901542-3 2009 Until recently, we have relied largely on the use of rapamycin to study mTOR function and its anticancer potential. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 72-76 19901542-4 2009 Recent insights now indicate that rapamycin is a partial inhibitor of mTOR through allosteric inhibition of mTOR complex-1 (mTORC1) but not mTOR complex-2 (mTORC2). Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 70-74 19901542-4 2009 Recent insights now indicate that rapamycin is a partial inhibitor of mTOR through allosteric inhibition of mTOR complex-1 (mTORC1) but not mTOR complex-2 (mTORC2). Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 108-112 19901542-4 2009 Recent insights now indicate that rapamycin is a partial inhibitor of mTOR through allosteric inhibition of mTOR complex-1 (mTORC1) but not mTOR complex-2 (mTORC2). Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 108-112 19901542-8 2009 The discovery of specific, active-site mTOR inhibitors has opened a new chapter in the 40-plus year old odyssey that began with the discovery of rapamycin from a soil sample collected on Easter Island (see Vezina C, et al. Sirolimus 145-154 mechanistic target of rapamycin kinase Homo sapiens 39-43 19892307-2 2009 METHODS: We treated 5 patients with chemotherapy-refractory AML with the mTOR-inhibitor rapamycin at 2mg per os daily for 14 days, with dose adjustment allowed to reach a target serum rapamycin concentration of 10-20 ng/mL. Sirolimus 88-97 mechanistic target of rapamycin kinase Homo sapiens 73-77 19892307-2 2009 METHODS: We treated 5 patients with chemotherapy-refractory AML with the mTOR-inhibitor rapamycin at 2mg per os daily for 14 days, with dose adjustment allowed to reach a target serum rapamycin concentration of 10-20 ng/mL. Sirolimus 184-193 mechanistic target of rapamycin kinase Homo sapiens 73-77 19875810-9 2009 Inhibition of mTOR by rapamycin or one of its analogues represents a potentially novel treatment for autosomal dominant polycystic kidney disease. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 19570961-2 2009 The evidence of upstream and/or downstream mammalian target of rapamycin (mTOR) pathway activation prompted us to combine an mTOR inhibitor, sirolimus, to IM in IM-resistant advanced chordoma. Sirolimus 141-150 mechanistic target of rapamycin kinase Homo sapiens 43-72 19892916-3 2009 We hypothesized that rapamycin, a specific inhibitor of mTOR, will maintain primary human oral keratinocytes as a small-sized, undifferentiated cell population capable of retaining their proliferative capacity. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 56-60 20195232-7 2009 Sirolimus (SRL) and everolimus constitute a new class of compounds designated as the mammalian target of rapamycin (mTOR) inhibitors, which exhibit immunosuppressive and antiproliferative effects. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 85-114 20195232-7 2009 Sirolimus (SRL) and everolimus constitute a new class of compounds designated as the mammalian target of rapamycin (mTOR) inhibitors, which exhibit immunosuppressive and antiproliferative effects. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 116-120 19632318-8 2009 Pretreatment with the phosphatidylinositol 3-kinase inhibitor Ly294002 and mTOR inhibitor rapamycin restored the ability of PDBu to downregulate PKC delta in HeLa/CP cells. Sirolimus 90-99 mechanistic target of rapamycin kinase Homo sapiens 75-79 19843663-0 2009 A phase I study of the mammalian target of rapamycin inhibitor sirolimus and MEC chemotherapy in relapsed and refractory acute myelogenous leukemia. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 23-52 19843663-2 2009 We sought to determine the safety and describe the toxicity of this approach by adding the mTOR inhibitor, sirolimus (rapamycin), to intensive AML induction chemotherapy. Sirolimus 107-116 mechanistic target of rapamycin kinase Homo sapiens 91-95 19843663-2 2009 We sought to determine the safety and describe the toxicity of this approach by adding the mTOR inhibitor, sirolimus (rapamycin), to intensive AML induction chemotherapy. Sirolimus 118-127 mechanistic target of rapamycin kinase Homo sapiens 91-95 19718660-7 2009 Cancer cells have a constitutively active mTOR pathway; surprisingly, inhibition of mTOR complex 1 (mTORC1) by rapamycin barely affects the global rate of translation and of initiation of translation, but deeply inhibits mesothelioma spreading on ECM. Sirolimus 111-120 mechanistic target of rapamycin kinase Homo sapiens 42-46 19718660-7 2009 Cancer cells have a constitutively active mTOR pathway; surprisingly, inhibition of mTOR complex 1 (mTORC1) by rapamycin barely affects the global rate of translation and of initiation of translation, but deeply inhibits mesothelioma spreading on ECM. Sirolimus 111-120 mechanistic target of rapamycin kinase Homo sapiens 84-88 19215663-9 2009 When the level of phosphorylation of the mammalian target of rapamycin (mTOR) was measured, down-regulation of phosphorylated mTOR levels was observed only in rapamycin-treated cells. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 72-76 19215663-9 2009 When the level of phosphorylation of the mammalian target of rapamycin (mTOR) was measured, down-regulation of phosphorylated mTOR levels was observed only in rapamycin-treated cells. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 126-130 19816606-1 2009 BACKGROUND: The mTOR inhibitor rapamycin has anti-tumor activity across a variety of human cancers, including hepatocellular carcinoma. Sirolimus 31-40 mechanistic target of rapamycin kinase Homo sapiens 16-20 19648118-5 2009 The mTOR inhibitor rapamycin suppresses the translation of some neuronal polarity proteins, including CRMP2 and Tau, thereby inhibiting axon formation. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 19641186-6 2009 Addition of the histone deacetylase inhibitor (HDI) LBH589 (LBH) overcame rapamycin resistance by blocking mTOR, thus preventing Akt activation. Sirolimus 74-83 mechanistic target of rapamycin kinase Homo sapiens 107-111 19785652-9 2009 The mTOR inhibitor LY294002, like rapamycin, decreased IP(3)-evoked Ca(2+) release. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 4-8 19761448-6 2009 Most importantly, however, if select focal cortical malformations result from enhanced mTOR signaling, new therapeutic antiepileptic compounds, such as rapamycin, can be designed and tested that specifically target mTOR signaling. Sirolimus 152-161 mechanistic target of rapamycin kinase Homo sapiens 87-91 19761448-6 2009 Most importantly, however, if select focal cortical malformations result from enhanced mTOR signaling, new therapeutic antiepileptic compounds, such as rapamycin, can be designed and tested that specifically target mTOR signaling. Sirolimus 152-161 mechanistic target of rapamycin kinase Homo sapiens 215-219 19724909-8 2009 PDGF-induced nuclear localization of mTOR was blocked by pre-treatment with RAPA. Sirolimus 76-80 mechanistic target of rapamycin kinase Homo sapiens 37-41 19665249-10 2009 Blockade of Ras and mTOR pathways with sorafenib and rapamycin reduced cell proliferation and induced apoptosis in cell lines. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 20-24 19702335-6 2009 The upregulation of Seryl-aminoacyl-tRNA-synthetase and Eef2 was sensitive to the mTOR inhibitor rapamycin, as determined by Western blot. Sirolimus 97-106 mechanistic target of rapamycin kinase Homo sapiens 82-86 19698731-5 2009 The levels of p-mTOR, cyclin D1, and p21(WAF1/CIP1/SDI1) as well as the aging-related phenotypes were all reduced in cells treated with rapamycin (an inhibitor of mTOR) than in control cells (P < 0.05). Sirolimus 136-145 mechanistic target of rapamycin kinase Homo sapiens 16-20 19698731-5 2009 The levels of p-mTOR, cyclin D1, and p21(WAF1/CIP1/SDI1) as well as the aging-related phenotypes were all reduced in cells treated with rapamycin (an inhibitor of mTOR) than in control cells (P < 0.05). Sirolimus 136-145 mechanistic target of rapamycin kinase Homo sapiens 163-167 19596836-5 2009 Treatment of TSC2-null tumors with mTOR inhibitor rapamycin attenuated STAT3 expression and phosphorylation. Sirolimus 50-59 mechanistic target of rapamycin kinase Homo sapiens 35-39 19954658-7 2009 (3) On exposure to RAPA, the levels of p-mTOR, p-S6 and IFN-gamma in T cells in refractory/relapsed AA patients were significantly lower than those before the exposure (all P < 0.05). Sirolimus 19-23 mechanistic target of rapamycin kinase Homo sapiens 41-45 19963096-4 2009 Temsirolimus is an ester analog of rapamycin that retains its potent intrinsic mTOR inhibitory activity while exhibiting better solubility for IV formulation. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 79-83 19963098-2 2009 mTOR is found in two different complexes within the cell, mTORC1 and mTORC2, but only mTORC1 is sensitive to inhibition by rapamycin. Sirolimus 123-132 mechanistic target of rapamycin kinase Homo sapiens 0-4 19940197-3 2009 Here, we show that persistent pain states, but not acute pain behavior, are substantially alleviated by centrally administered rapamycin, an inhibitor of the mTOR pathway. Sirolimus 127-136 mechanistic target of rapamycin kinase Homo sapiens 158-162 19940197-6 2009 Intrathecal injections of rapamycin inhibited the activation of downstream targets of mTOR in dorsal horn and dorsal roots and reduced the thermal sensitivity of A-fibers. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 86-90 19570961-2 2009 The evidence of upstream and/or downstream mammalian target of rapamycin (mTOR) pathway activation prompted us to combine an mTOR inhibitor, sirolimus, to IM in IM-resistant advanced chordoma. Sirolimus 141-150 mechanistic target of rapamycin kinase Homo sapiens 74-78 19570961-2 2009 The evidence of upstream and/or downstream mammalian target of rapamycin (mTOR) pathway activation prompted us to combine an mTOR inhibitor, sirolimus, to IM in IM-resistant advanced chordoma. Sirolimus 141-150 mechanistic target of rapamycin kinase Homo sapiens 125-129 19651486-7 2009 The mTOR inhibitors (sirolimus and everolimus) have different side effects (hyperlipidemia, thrombocytopenia, and pulmonary, cutaneous, and articular events) than ACNs. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 4-8 19524688-4 2009 Rapamycin exerts its biological activity by inhibiting the serine-threonine kinase mTOR, which regulates important cellular processes such as control of cell cycle, cell size, translation initiation and transcription. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 83-87 19524688-5 2009 The ability of rapamycin to cause G1-cell cycle arrest, reduced cell growth and a reduced rate of proliferation has led to efforts to develop rapamycin and related mTOR inhibitors as anti-cystogenesis agents. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 164-168 19607806-4 2009 Treatment with the mTOR inhibitor, rapamycin, inhibited this CCL5-inducible proliferation. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 19-23 19584709-0 2009 Rapamycin, the mTOR kinase inhibitor, sensitizes acute myeloid leukemia cells, HL-60 cells, to the cytotoxic effect of arabinozide cytarabine. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 15-19 19645448-2 2009 Rapamycin and its analogues, allosteric inhibitors of mTOR, only partially inhibit one mTOR protein complex. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 54-58 19645448-2 2009 Rapamycin and its analogues, allosteric inhibitors of mTOR, only partially inhibit one mTOR protein complex. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 87-91 19535330-4 2009 OGD-induced apoptosis was increased by the combined deletion of S6K1 and S6K2 genes, as well as by treatment with rapamycin that inhibits S6K1 activity by acting on the upstream regulator mTOR (mammalian target of rapamycin). Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 188-192 19523443-1 2009 Rapamycin is an immunosuppressive drug, which inhibits the mammalian target of rapamycin (mTOR) kinase activity inducing changes in cell proliferation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 59-88 19523443-1 2009 Rapamycin is an immunosuppressive drug, which inhibits the mammalian target of rapamycin (mTOR) kinase activity inducing changes in cell proliferation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 90-94 19535330-4 2009 OGD-induced apoptosis was increased by the combined deletion of S6K1 and S6K2 genes, as well as by treatment with rapamycin that inhibits S6K1 activity by acting on the upstream regulator mTOR (mammalian target of rapamycin). Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 194-223 19625624-2 2009 Rapamycin promotes feedback activation of Akt in some patients, potentially underlying clinical resistance and raising the need for alternative approaches to block mTOR signaling. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 164-168 19375241-13 2009 In addition, rapamycin is a selective and effective mammalian target of rapamycin (mTOR) inhibitor. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 52-81 19549188-5 2009 However, the mode of action of E1 is different from that of the mTOR inhibitor rapamycin. Sirolimus 79-88 mechanistic target of rapamycin kinase Homo sapiens 64-68 19808140-2 2009 Sirolimus, the principal metabolite of temsirolimus in humans, also exhibits mTOR inhibitory activity. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 77-81 19220580-9 2009 Treatment of 10-0505 tumours with sorafenib plus rapamycin resulted in growth inhibition, inhibition of vascular endothelial growth factor receptor-2 phosphorylation, increased apoptosis and completely blocked sorafenib-induced phosphorylation of mTOR targets and cyclin B1 expression. Sirolimus 49-58 mechanistic target of rapamycin kinase Homo sapiens 247-251 19375241-13 2009 In addition, rapamycin is a selective and effective mammalian target of rapamycin (mTOR) inhibitor. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 83-87 19586661-2 2009 mTOR signals via two complexes: TORC1, which contains the Regulatory Associated Protein of TOR (raptor), and TORC2, which contains the Rapamycin-insensitive Companion of TOR (rictor). Sirolimus 135-144 mechanistic target of rapamycin kinase Homo sapiens 0-4 19586661-3 2009 The immunosuppressive/anti-cancer agent rapamycin inhibits TORC1 function by disrupting the mTOR-raptor interaction. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 92-96 19321761-9 2009 Mammalian target of rapamycin (mTOR) activation in the heart, as evidenced by a marked increase in the phospho-S6 protein that was inhibited by rapamycin, was demonstrated in 12-month-old Cy/+ rats. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 31-35 19286253-6 2009 Consequently, e.g. clinical trials for the treatment with rapamycin, a negative regulator of mTOR, of hamartomas in TSC have already been initiated. Sirolimus 58-67 mechanistic target of rapamycin kinase Homo sapiens 93-97 19406104-5 2009 Inhibition of mTOR by rapamycin notably increased the level of phosphorylated eEF2 in infected cells. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 19108833-5 2009 RESULTS: mTOR and its downstream target p70S6 kinase are phosphorylated and activated by mitogenic concentrations of oxLDL (50 microg/ml), and are involved in SMC proliferation, as assessed by the inhibitory effect of the mTOR inhibitor rapamycin. Sirolimus 237-246 mechanistic target of rapamycin kinase Homo sapiens 9-13 19483651-3 2009 In particular, rapamycin, is a well-known immunosuppressant that can decrease the activity of the PI3K/mTOR pathway in tumor cells, but also has a profound inhibitory effect on T cells. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 103-107 19421190-1 2009 Because the size of renal cysts in the native kidneys of patients with ADPKD who have been transplanted was found to be reduced when rapamycin was the immunosuppressant, we tested the involvement of the mTOR pathway in cyst enlargement. Sirolimus 133-142 mechanistic target of rapamycin kinase Homo sapiens 203-207 19522662-1 2009 Sirolimus is an antiproliferative immunosuppressive agent that inhibits the mammalian target of rapamycin. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 76-105 19651290-7 2009 It is anticipated that the inhibition of mTOR with sirolimus can slow disease progression and delay the need for chronic renal replacement therapy. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 41-45 19410601-11 2009 However, this mechanism is not sufficient to explain the high LC3-II activation caused by dopamine: the LC3-II increase was not reversed by IGF-1, which prevented this effect when caused by the mTOR inhibitor rapamycin. Sirolimus 209-218 mechanistic target of rapamycin kinase Homo sapiens 194-198 19557637-6 2009 Because rapamycin targets the mammalian target of rapamycin (mTOR) pathway, we also used our cells to confirm that rapamycin modified the expression of mTOR and effectively suppressed the phosphorylation of two downstream effector molecules in the mTOR pathway, S6K1, and 4E-BP1. Sirolimus 8-17 mechanistic target of rapamycin kinase Homo sapiens 30-59 19557637-6 2009 Because rapamycin targets the mammalian target of rapamycin (mTOR) pathway, we also used our cells to confirm that rapamycin modified the expression of mTOR and effectively suppressed the phosphorylation of two downstream effector molecules in the mTOR pathway, S6K1, and 4E-BP1. Sirolimus 8-17 mechanistic target of rapamycin kinase Homo sapiens 61-65 19557637-6 2009 Because rapamycin targets the mammalian target of rapamycin (mTOR) pathway, we also used our cells to confirm that rapamycin modified the expression of mTOR and effectively suppressed the phosphorylation of two downstream effector molecules in the mTOR pathway, S6K1, and 4E-BP1. Sirolimus 8-17 mechanistic target of rapamycin kinase Homo sapiens 152-156 19557637-6 2009 Because rapamycin targets the mammalian target of rapamycin (mTOR) pathway, we also used our cells to confirm that rapamycin modified the expression of mTOR and effectively suppressed the phosphorylation of two downstream effector molecules in the mTOR pathway, S6K1, and 4E-BP1. Sirolimus 8-17 mechanistic target of rapamycin kinase Homo sapiens 152-156 19302577-3 2009 Toxoplasma invasion of multiple cell types rapidly induced sustained mTOR activation that was restricted to infected cells, as determined by rapamycin-sensitive phosphorylation of ribosomal protein S6; however, phosphorylation of the growth-associated mTOR substrates 4E-BP1 and S6K1 was not detected. Sirolimus 141-150 mechanistic target of rapamycin kinase Homo sapiens 69-73 19331815-5 2009 Rapamycin inhibited mTOR kinase activity as demonstrated with a lower phosphorylation level of the mTOR substrate p70 S6 kinase (S6K). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 20-24 19331815-5 2009 Rapamycin inhibited mTOR kinase activity as demonstrated with a lower phosphorylation level of the mTOR substrate p70 S6 kinase (S6K). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 99-103 19339632-9 2009 Inhibition of the PI3K pathways by the selective PI3K inhibitor LY 294002, an Akt inhibitor, or the mTOR inhibitor rapamycin reduced cell proliferation by 51%. Sirolimus 115-124 mechanistic target of rapamycin kinase Homo sapiens 100-104 19302070-1 2009 Sirolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is increasingly used as an agent for post-transplant immunosuppression and the treatment of solid organ and haematological malignancies and hamartomas. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 31-60 19302070-1 2009 Sirolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is increasingly used as an agent for post-transplant immunosuppression and the treatment of solid organ and haematological malignancies and hamartomas. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 62-66 19553465-6 2009 The present study targeted the mammalian target of rapamycin (mTOR) signaling pathway, which regulates cell growth and is blocked by rapamycin. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 62-66 19478560-1 2009 Inhibition of mTOR by rapamycin prevents cellular senescence. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 19483303-1 2009 We investigated the effect of rapamycin, a specific inhibitor of the mammalian serine/threonine kinase, mammalian target of rapamycin (mTOR), on the expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 104-133 19483303-1 2009 We investigated the effect of rapamycin, a specific inhibitor of the mammalian serine/threonine kinase, mammalian target of rapamycin (mTOR), on the expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 135-139 19166929-1 2009 The mammalian target of rapamycin (mTOR) signalling pathway is implicated in the pathogenesis of a number of cancers and inherited hamartoma syndromes which have led to mTOR inhibitors, such as rapamycin, being tested in clinical trials. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 35-39 19166929-1 2009 The mammalian target of rapamycin (mTOR) signalling pathway is implicated in the pathogenesis of a number of cancers and inherited hamartoma syndromes which have led to mTOR inhibitors, such as rapamycin, being tested in clinical trials. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 169-173 19302577-7 2009 In spite of a failure to phosphorylate 4E-BP1 and S6K1, intracellular T. gondii triggered host cell cycle progression in an mTOR-dependent manner and progression of infected cells displayed increased sensitivity to rapamycin. Sirolimus 215-224 mechanistic target of rapamycin kinase Homo sapiens 124-128 19229543-2 2009 This study addresses the effect of AZA and RPM combination therapy on CRC and its influence on the mammalian target of rapamycin (mTOR) and its signal transduction pathway. Sirolimus 43-46 mechanistic target of rapamycin kinase Homo sapiens 99-128 19458076-4 2009 Here, we examined the effect of targeting mTOR by rapamycin and/or MEK by PD184352 in human glioblastoma cell lines. Sirolimus 50-59 mechanistic target of rapamycin kinase Homo sapiens 42-46 19272638-17 2009 These findings warrant further investigation and suggest a potential role for therapeutic agents targeting the PI3K-AKT-mTOR pathway, such as rapamycin, as well as possible targets of EGFR in the treatment of uterine serous carcinoma. Sirolimus 142-151 mechanistic target of rapamycin kinase Homo sapiens 120-124 19229543-2 2009 This study addresses the effect of AZA and RPM combination therapy on CRC and its influence on the mammalian target of rapamycin (mTOR) and its signal transduction pathway. Sirolimus 43-46 mechanistic target of rapamycin kinase Homo sapiens 130-134 19347904-1 2009 mTOR pathway inhibitors, specifically rapamycin and its derivatives, are promising therapeutics that targets downstream pathways including protein translation. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 0-4 19424604-9 2009 In addition, the mTOR inhibitor rapamycin was found to affect the phosphorylation status of p70S6K in amniotic fluid stem cells. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 17-21 19474323-7 2009 The mTOR inhibitor rapamycin, administered before kainate, blocked both the acute and chronic phases of seizure-induced mTOR activation and decreased kainate-induced neuronal cell death, neurogenesis, mossy fiber sprouting, and the development of spontaneous epilepsy. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 19539245-7 2009 When compared with monotherapy, combinatorial application of rapamycin and PD98059 had greater inhibitory effects on Tsc2 deficient cell proliferation, suggesting that combined suppression of mTOR and ERK/MAPK signaling pathways may have advantages over single mTOR inhibition in the treatment of TSC patients. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 192-196 19539245-7 2009 When compared with monotherapy, combinatorial application of rapamycin and PD98059 had greater inhibitory effects on Tsc2 deficient cell proliferation, suggesting that combined suppression of mTOR and ERK/MAPK signaling pathways may have advantages over single mTOR inhibition in the treatment of TSC patients. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 261-265 19474323-7 2009 The mTOR inhibitor rapamycin, administered before kainate, blocked both the acute and chronic phases of seizure-induced mTOR activation and decreased kainate-induced neuronal cell death, neurogenesis, mossy fiber sprouting, and the development of spontaneous epilepsy. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 120-124 19150980-3 2009 Here we find that Torin1, a highly potent and selective ATP-competitive mTOR inhibitor that directly inhibits both complexes, impairs cell growth and proliferation to a far greater degree than rapamycin. Sirolimus 193-202 mechanistic target of rapamycin kinase Homo sapiens 72-76 19402072-8 2009 Possible mechanisms include the loss of feedback inhibition of insulin receptor substate/PI3K signaling resulting from the inhibition of mTOR complex 1 by rapamycin analogs and the activating phosphorylation of Akt by mTOR complex 2. Sirolimus 155-164 mechanistic target of rapamycin kinase Homo sapiens 137-141 19245654-4 2009 Recent work has revealed that across eukaryotes mTOR orthologues are found in two biochemically distinct complexes and only one of those complexes (mTORC1 in mammals) is acutely sensitive to rapamycin and regulated by nutrients and AMPK. Sirolimus 191-200 mechanistic target of rapamycin kinase Homo sapiens 48-52 19120326-0 2009 Suppression of mTOR complex 2-dependent AKT phosphorylation in melanoma cells by combined treatment with rapamycin and LY294002. Sirolimus 105-114 mechanistic target of rapamycin kinase Homo sapiens 15-19 19389529-0 2009 Significant response after treatment with the mTOR inhibitor sirolimus in combination with carboplatin and paclitaxel in metastatic melanoma patients. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 46-50 19389529-5 2009 We report two cases of patients with metastatic melanoma who showed significant remission after combination of carboplatin and paclitaxel with the mTOR inhibitor sirolimus. Sirolimus 162-171 mechanistic target of rapamycin kinase Homo sapiens 147-151 19412427-11 2009 Low-dose sunitinib (20 mg/kg) demonstrates synergistic cytotoxicity with an mTOR inhibitor, rapamycin, which is more effective than the traditional chemotherapeutic drug, cyclophosphamide. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 76-80 19384185-2 2009 Sirolimus (SRL) is a non-nephrotoxic immunosuppressive drug blocking T-cell proliferation through mTOR inhibition. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 98-102 19368729-3 2009 Early clinical trials show that TSC-related kidney tumors (angiomyolipomas) regress when treated with the mammalian target of rapamycin (mTOR) inhibitor, rapamycin (also known as sirolimus). Sirolimus 126-135 mechanistic target of rapamycin kinase Homo sapiens 137-141 19368729-3 2009 Early clinical trials show that TSC-related kidney tumors (angiomyolipomas) regress when treated with the mammalian target of rapamycin (mTOR) inhibitor, rapamycin (also known as sirolimus). Sirolimus 179-188 mechanistic target of rapamycin kinase Homo sapiens 106-135 19368729-3 2009 Early clinical trials show that TSC-related kidney tumors (angiomyolipomas) regress when treated with the mammalian target of rapamycin (mTOR) inhibitor, rapamycin (also known as sirolimus). Sirolimus 179-188 mechanistic target of rapamycin kinase Homo sapiens 137-141 19190264-4 2009 This effect of insulin on lipolysis was only observed when the mammalian target of rapamycin (mTOR) pathway was inhibited by rapamycin in the adipocytes. Sirolimus 83-92 mechanistic target of rapamycin kinase Homo sapiens 94-98 19414357-1 2009 Rapamycin, an inhibitor of mTOR, is in clinical trials for treatment of cancer. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 19414357-4 2009 Rapamycin inhibition of cell proliferation, the cell cycle and mTOR signaling, including p70S6 and S6RP phosphorylation, was most effective in benign (MCF10A) and premalignant (MCF10AT; MCF10ATG3B) human breast epithelial cells, relative to MCF10CA1a tumor cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 63-67 19154728-1 2009 The calcineurin inhibitors cyclosporin A and tacrolimus and the inhibitors of the mTOR, sirolimus and everolimus bind immunophilins that are required for their immunosuppressive action. Sirolimus 88-97 mechanistic target of rapamycin kinase Homo sapiens 82-86 19208097-1 2009 We hypothesized that sirolimus, an mTOR inhibitor, may be effective in patients with autoimmune lymphoproliferative syndrome (ALPS) and treated patients who were intolerant to or failed other therapies. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 35-39 19013721-6 2009 Inhibition of mTOR by rapamycin (a natural product) or its analogs aims to prevent the deleterious effects of the abnormal signaling, regardless at which point of the signal pathway has the abnormality launched. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 19270529-2 2009 A recent study revealing mechanistically how rapamycin suppresses mTOR provides two explanations for the differential sensitivities to rapamycin. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 66-70 19356713-5 2009 Insulin resistance induced by HF/BCAA feeding was accompanied by chronic phosphorylation of mTOR, JNK, and IRS1Ser307 and by accumulation of multiple acylcarnitines in muscle, and it was reversed by the mTOR inhibitor, rapamycin. Sirolimus 219-228 mechanistic target of rapamycin kinase Homo sapiens 203-207 19211763-3 2009 However, although the mTOR inhibitor rapamycin suppressed VV-induced inactivation of 4E-BP1, it failed to inhibit eIF4F assembly. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 22-26 19225151-6 2009 Inhibition of mTOR by rapamycin or leucine deprivation, the conditions that induce autophagy, leads to dephosphorylation of ULK1, ULK2, and Atg13 and activates ULK to phosphorylate FIP200. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 19379572-6 2009 PCR results showed the down-regulation of mTOR, cyclin D1 and mTOR mRNA expressions after treating RPMI8226 cells with different concentrations of rapamycin for 24 hours. Sirolimus 147-156 mechanistic target of rapamycin kinase Homo sapiens 42-46 19379572-6 2009 PCR results showed the down-regulation of mTOR, cyclin D1 and mTOR mRNA expressions after treating RPMI8226 cells with different concentrations of rapamycin for 24 hours. Sirolimus 147-156 mechanistic target of rapamycin kinase Homo sapiens 62-66 19331694-9 2009 In contrast, rapamycin, an inhibitor of mTOR, blocked phosphorylation only of Ser65 and Thr70. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 40-44 19435890-2 2009 Thus, mTOR inhibition by rapamycin or TSC1/2 results in increased PI3K-Akt activation. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 6-10 19420259-2 2009 The TSC1/TSC2 protein complex plays a major role in controlling the Ser/Thr kinase mammalian target of rapamycin (mTOR), which is a master regulator of protein synthesis and cell growth. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 114-118 19285959-5 2009 We found that FGFR1 activated Akt/mTOR pathway and that the mTOR inhibitor rapamycin partially reversed FGFR1-mediated downregulation of SM marker gene expression. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 60-64 19261747-4 2009 Furthermore, the synergistic effects of p53 and Pten deletion are mediated by deregulation of mammalian target of rapamycin (mTOR) signaling, consistent with the ability of rapamycin to block bladder tumorigenesis in preclinical studies. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 125-129 19293429-6 2009 Rapamycin treatment of diet-induced obese mice or of transgenic mice with long-term activation of endothelial Akt inhibits activation of mammalian target of rapamycin (mTOR)-rictor complex 2 and Akt, prevents vascular senescence without altering body weight, and reduces the severity of limb necrosis and ischemic stroke. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 137-166 19293429-6 2009 Rapamycin treatment of diet-induced obese mice or of transgenic mice with long-term activation of endothelial Akt inhibits activation of mammalian target of rapamycin (mTOR)-rictor complex 2 and Akt, prevents vascular senescence without altering body weight, and reduces the severity of limb necrosis and ischemic stroke. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 168-172 19151764-3 2009 Although mTOR inhibitor, rapamycin, has been widely used to inhibit the aberrant signaling due to mTOR activation that plays a major role in hyperproliferative diseases, in some cases rapamycin does not attenuate the cell proliferation and survival. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 9-13 19276265-6 2009 We also tested the efficacy of the mTOR inhibitor rapamycin on signaling and growth of chordoma cell lines. Sirolimus 50-59 mechanistic target of rapamycin kinase Homo sapiens 35-39 19112174-1 2009 The 40 S ribosomal S6 kinase 1 (S6K1) acts downstream of mTOR (mammalian target of rapamycin) and is sensitive to inhibition by rapamycin. Sirolimus 83-92 mechanistic target of rapamycin kinase Homo sapiens 57-61 19151764-3 2009 Although mTOR inhibitor, rapamycin, has been widely used to inhibit the aberrant signaling due to mTOR activation that plays a major role in hyperproliferative diseases, in some cases rapamycin does not attenuate the cell proliferation and survival. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 98-102 19151764-5 2009 Our data show that in a variety of cell types the mTOR inhibitor rapamycin activates extracellularly regulated kinases (Erk1/2) signaling. Sirolimus 65-74 mechanistic target of rapamycin kinase Homo sapiens 50-54 18783828-0 2009 Hypersensitivity of Ph-positive lymphoid cell lines to rapamycin: Possible clinical application of mTOR inhibitor. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 99-103 19244117-8 2009 Thus, phospho-S2481 on mTOR serves as a biomarker for intact mTORC2 and its sensitivity to rapamycin. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 23-27 18783828-5 2009 Here, we report that the serine/threonine kinase mTOR (the mammalian target of rapamycin) inhibitor, rapamycin, inhibits the growth of not only the Bcr-Abl-positive lymphoid leukemic cell line, SU-Ph2, established from Ph(+)ALL patients, but also the imatinib-resistant cell line, SU/SR, that has acquired T315I. Sirolimus 79-88 mechanistic target of rapamycin kinase Homo sapiens 49-53 19114562-9 2009 Data provided here demonstrate a PA requirement for the stabilization of both mTORC1 and mTORC2 complexes and reveal a mechanism for the inhibitory effect of rapamycin on mTOR. Sirolimus 158-167 mechanistic target of rapamycin kinase Homo sapiens 78-82 19250527-5 2009 In the tissue culture system, we detected significantly elevated Foxp3 expression and IL-10 production, as well as an increased percentage of Foxp3+ Tregs in nasal polyps after blocking the mTOR signaling pathway with rapamycin. Sirolimus 218-227 mechanistic target of rapamycin kinase Homo sapiens 190-194 17990907-4 2009 Recently, some trials treating TSC with the mTOR inhibitor rapamycin have been published; however, the impact of such treatment on heart tumors is not known. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 44-48 19019920-10 2009 Our data provide new molecular insights explaining which pathways and molecules are affected in podocytes by an imbalanced mTOR function because of rapamycin treatment. Sirolimus 148-157 mechanistic target of rapamycin kinase Homo sapiens 123-127 18713146-2 2009 Its immunosuppression regimen was largely based on the mTOR inhibitor rapamycin (sirolimus), which remains the most frequently used immunosuppressive drug in clinical islet transplant protocols. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 55-59 19074484-5 2009 mTOR inhibition with rapamycin at below pharmacological concentrations blocked p70S6K phosphorylation and induced a differentiated contractile phenotype with smooth muscle (sm)-calponin, sm-alpha-actin, and SM protein 22-alpha (SM22alpha) expression. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 0-4 19028034-5 2009 Rapamycin normalizes the dysregulated mTOR pathway, and recent clinical trials have demonstrated its efficacy in various TSC manifestations, suggesting the possibility that rapamycin may have benefit in the treatment of TSC brain disease. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 38-42 19028034-5 2009 Rapamycin normalizes the dysregulated mTOR pathway, and recent clinical trials have demonstrated its efficacy in various TSC manifestations, suggesting the possibility that rapamycin may have benefit in the treatment of TSC brain disease. Sirolimus 173-182 mechanistic target of rapamycin kinase Homo sapiens 38-42 19177002-4 2009 PI-103 and the mTOR inhibitor rapamycin both inhibited ribosomal protein S6 phosphorylation but there were clear differences in the response of upstream components of the PI3 kinase pathway, such as phosphorylation of Thr(308)-AKT, that were inhibited by PI-103 but not rapamycin. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 15-19 19177002-4 2009 PI-103 and the mTOR inhibitor rapamycin both inhibited ribosomal protein S6 phosphorylation but there were clear differences in the response of upstream components of the PI3 kinase pathway, such as phosphorylation of Thr(308)-AKT, that were inhibited by PI-103 but not rapamycin. Sirolimus 270-279 mechanistic target of rapamycin kinase Homo sapiens 15-19 19148492-11 2009 Rapamycin also down-regulated the activity of p70S6, pAkt and p-mTOR, but had no effect on pGSK-3beta, p44Erk, pCdc2, TSC1/2 or Hsp70 or Hsp90. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 64-68 19190120-8 2009 Similarly, combining a monoclonal anti-HGF antibody (L2G7) with the mTOR inhibitor rapamycin had additive inhibitory effects on glioblastoma cell proliferation. Sirolimus 83-92 mechanistic target of rapamycin kinase Homo sapiens 68-72 18927120-1 2009 BACKGROUND: The specific mTor inhibitor sirolimus has been implicated in the pathogenesis of renal glomerular lesions and nephrotic syndrome appearance after transplantation. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 25-29 18713146-2 2009 Its immunosuppression regimen was largely based on the mTOR inhibitor rapamycin (sirolimus), which remains the most frequently used immunosuppressive drug in clinical islet transplant protocols. Sirolimus 81-90 mechanistic target of rapamycin kinase Homo sapiens 55-59 19147764-3 2009 This study tested the hypothesis that rapamycin radiosensitizes soft tissue sarcoma and endothelial cells in vitro and in vivo through the inhibition of mTOR. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 153-157 19165201-5 2009 We show that this subset of NSCLC is also sensitised to the mTOR inhibitor rapamycin. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 60-64 19276368-9 2009 Together, using rapamycin phosphoproteomics, we not only advance the global mechanistic understanding of the action of rapamycin but also show that CDC25B may serve as a drug target for improving mTOR-targeted cancer therapies. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 196-200 19147764-11 2009 CONCLUSIONS: Minimally cytotoxic concentrations of rapamycin inhibited the mTOR cascade in culture and in vivo while radiosensitizing soft tissue sarcoma, and produced synergistic effects with radiation on HDMEC microvessel formation. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 75-79 19211363-3 2009 Rapamycin is an inhibitor of mTOR that has first been developed for its immunosuppressive characteristics, as a preventive treatment of graft rejection. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 29-33 18987252-4 2009 Inhibition of mTOR by rapamycin significantly reduced the activity of system A (-17%), system L (-28%), and taurine (-40%) amino acid transporters. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 19489650-5 2009 The immunosuppressant sirolimus (rapamycin) directly inhibits mTOR activity and suppresses the growth of cancer cells in vitro and in vivo. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 62-66 19489650-5 2009 The immunosuppressant sirolimus (rapamycin) directly inhibits mTOR activity and suppresses the growth of cancer cells in vitro and in vivo. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 62-66 19090006-12 2009 Overall, the current results demonstrated the potential for the application of rapamycin, an mTOR inhibitor, as an additional novel component of chemotherapy for a defined subset of patients with lung carcinoma. Sirolimus 79-88 mechanistic target of rapamycin kinase Homo sapiens 93-97 19117990-6 2009 Rapamycin, the pharmacologic inhibitor of mTOR, prevents TGF-beta-mediated anchorage-independent growth without affecting TGF-beta transcriptional responses or extracellular matrix protein induction. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 42-46 18636076-3 2009 Autophagy is negatively regulated by the mammalian target of rapamycin (mTOR) and can be induced in all mammalian cell types by the mTOR inhibitor rapamycin. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 72-76 19139015-7 2009 Furthermore, we show that the inhibition of mTOR by the chronic administration of rapamycin halts the malignant conversion of precancerous lesions and promotes the regression of advanced carcinogen-induced SCCs. Sirolimus 82-91 mechanistic target of rapamycin kinase Homo sapiens 44-48 18636076-3 2009 Autophagy is negatively regulated by the mammalian target of rapamycin (mTOR) and can be induced in all mammalian cell types by the mTOR inhibitor rapamycin. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 132-136 19705921-2 2009 In part II, we review the pharmacokinetics and therapeutic drug monitoring of mycophenolate and mammalian target of rapamycin inhibitors--sirolimus and everolimus--in thoracic transplantation, and we provide an overall discussion and suggest various areas for future study. Sirolimus 138-147 mechanistic target of rapamycin kinase Homo sapiens 96-125 19118035-10 2009 Treatment with the PI3K inhibitors LY294002 or wortmannin resulted in nuclear relocalization of p27, whereas mTOR inhibition by rapamycin did not. Sirolimus 128-137 mechanistic target of rapamycin kinase Homo sapiens 109-113 18781596-9 2009 Thus, activation of HIF-1alpha in exponentially growing cells via hypoxic stimulation is independent of the Akt/mTOR pathway whereas HIF-1alpha activation obtained in high confluency is totally dependent on mTOR pathway as rapamycin totally impaired (i) HIF-1alpha stabilization and (ii) mRNA levels of CA9 and BNIP3, two HIF-target genes. Sirolimus 223-232 mechanistic target of rapamycin kinase Homo sapiens 207-211 19430174-1 2009 We attempted a switch of mammalian target of rapamycin (mTOR) inhibitors from sirolimus to everolimus, a derivative of sirolimus and now on the market in Japan, in two pancreatic islet transplant patients. Sirolimus 78-87 mechanistic target of rapamycin kinase Homo sapiens 25-54 19430174-1 2009 We attempted a switch of mammalian target of rapamycin (mTOR) inhibitors from sirolimus to everolimus, a derivative of sirolimus and now on the market in Japan, in two pancreatic islet transplant patients. Sirolimus 78-87 mechanistic target of rapamycin kinase Homo sapiens 56-60 19430174-1 2009 We attempted a switch of mammalian target of rapamycin (mTOR) inhibitors from sirolimus to everolimus, a derivative of sirolimus and now on the market in Japan, in two pancreatic islet transplant patients. Sirolimus 119-128 mechanistic target of rapamycin kinase Homo sapiens 25-54 19430174-1 2009 We attempted a switch of mammalian target of rapamycin (mTOR) inhibitors from sirolimus to everolimus, a derivative of sirolimus and now on the market in Japan, in two pancreatic islet transplant patients. Sirolimus 119-128 mechanistic target of rapamycin kinase Homo sapiens 56-60 19834275-6 2009 Sirolimus, an mTOR protein inhibitor, was used to treat epithelioid AML. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 19129735-1 2009 Clinical studies of drug-eluting stents delivering the mammalian target of rapamycin (mTOR) inhibitor, rapamycin (Sirolimus), have demonstrated a reduced efficacy for these devices in patients with diabetes, which suggests that the mTOR pathway may cease to be dominant in mediating the vascular response to injury under diabetic conditions. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 86-90 19129735-1 2009 Clinical studies of drug-eluting stents delivering the mammalian target of rapamycin (mTOR) inhibitor, rapamycin (Sirolimus), have demonstrated a reduced efficacy for these devices in patients with diabetes, which suggests that the mTOR pathway may cease to be dominant in mediating the vascular response to injury under diabetic conditions. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 232-236 19129735-1 2009 Clinical studies of drug-eluting stents delivering the mammalian target of rapamycin (mTOR) inhibitor, rapamycin (Sirolimus), have demonstrated a reduced efficacy for these devices in patients with diabetes, which suggests that the mTOR pathway may cease to be dominant in mediating the vascular response to injury under diabetic conditions. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 55-84 19129735-1 2009 Clinical studies of drug-eluting stents delivering the mammalian target of rapamycin (mTOR) inhibitor, rapamycin (Sirolimus), have demonstrated a reduced efficacy for these devices in patients with diabetes, which suggests that the mTOR pathway may cease to be dominant in mediating the vascular response to injury under diabetic conditions. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 86-90 19129735-1 2009 Clinical studies of drug-eluting stents delivering the mammalian target of rapamycin (mTOR) inhibitor, rapamycin (Sirolimus), have demonstrated a reduced efficacy for these devices in patients with diabetes, which suggests that the mTOR pathway may cease to be dominant in mediating the vascular response to injury under diabetic conditions. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 232-236 19200882-3 2009 mTORC1 activity is inhibited by rapamycin, a specific inhibitor of mTOR, whereas mTORC2 activity is resistant to short-term treatments with rapamycin. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 0-4 19827268-6 2009 Resveratrol reduced phosphorylation of ribosomal protein S6 and the mTOR inhibitor rapamycin further enhanced resveratrol-induced cell death. Sirolimus 83-92 mechanistic target of rapamycin kinase Homo sapiens 68-72 20066897-1 2009 The cytotoxic effects and mechanism of action of cisplatin and the mTOR inhibitor rapamycin on Hep-2 laryngeal cancer cells were investigated. Sirolimus 82-91 mechanistic target of rapamycin kinase Homo sapiens 67-71 20419051-3 2009 Recent work implicates the mammalian target of rapamycin (mTOR) pathway as mediating epileptogenesis in a genetic epilepsy, Tuberous Sclerosis Complex (TSC), and suggests that mTOR inhibitors, such as rapamycin, may have antiepileptogenic properties for epilepsy in TSC. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 58-62 20419051-3 2009 Recent work implicates the mammalian target of rapamycin (mTOR) pathway as mediating epileptogenesis in a genetic epilepsy, Tuberous Sclerosis Complex (TSC), and suggests that mTOR inhibitors, such as rapamycin, may have antiepileptogenic properties for epilepsy in TSC. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 176-180 20419051-5 2009 Here, we describe evidence from a recently-published study that mTOR mediates epileptogenesis in a popular animal model of acquired limbic epilepsy due to brain injury following kainate-induced status epilepticus, and that rapamycin has antiepileptogenic effects in this model. Sirolimus 223-232 mechanistic target of rapamycin kinase Homo sapiens 64-68 19125612-6 2009 Treatment with the mTOR inhibitor rapamycin reduced the p-mTOR level by 25% after 4-24 h of incubation. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 19-23 19125612-6 2009 Treatment with the mTOR inhibitor rapamycin reduced the p-mTOR level by 25% after 4-24 h of incubation. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 58-62 20066897-6 2009 p-mTOR and S6K expressions were significantly downregulated by rapamycin. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 2-6 20066897-8 2009 Combined cisplatin and rapamycin treatment resulted in significant downregulated p-mTOR and S6K expression, but no change in ERCC1 expression. Sirolimus 23-32 mechanistic target of rapamycin kinase Homo sapiens 83-87 20066897-10 2009 Rapamycin may facilitate increased Hep-2 cell apoptosis with cisplatin via inhibiting downstream expression of proteins in the AKT-mTOR signaling pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 131-135 19293927-9 2009 S9 also completely impeded hyper-phosphorylation of Akt as a feedback of inhibition of mTOR by rapamycin. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 87-91 18945681-5 2008 mTOR exists in two complexes, mTORC1 and mTORC2, which are differentially sensitive to rapamycin. Sirolimus 87-96 mechanistic target of rapamycin kinase Homo sapiens 0-4 19149738-3 2009 Currently, the mTOR inhibitor rapamycin and its analogs have been vigorously evaluated and developed as anticancer drugs. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 15-19 20641681-8 2004 For example, PAI-2 (triciribine) and perifosine are potent and selective inhibitors of Akt, rapamycin is an inhibitor for downstream mTOR, and LY294002 is an inhibitor for upstream PI3K. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 133-137 19077306-12 2008 Pin1 inhibition greatly increased the sensitivity of Her2-positive breast cancer cells to the mTOR inhibitor Rapamycin, while it did not increase their sensitivity to Trastuzumab, suggesting that Pin1 might act on Her2 signaling. Sirolimus 109-118 mechanistic target of rapamycin kinase Homo sapiens 94-98 19020099-6 2008 Leptin significantly increases the dose of the mTOR inhibitor sirolimus that is required for effective inhibition of neointimal formation. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 47-51 19001324-2 2008 Sirolimus, an mTOR inhibitor, also has activity in the treatment and prophylaxis of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem-cell transplantation (HSCT). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 18809972-4 2008 In contrast, eIF4E phosphorylation is low in PC3 and LNCaP cells with mutated PTEN and constitutively active AKT/mTOR pathway, but it can be strongly induced through inhibition of mTOR activity by rapamycin or serum depletion. Sirolimus 197-206 mechanistic target of rapamycin kinase Homo sapiens 180-184 19020722-10 2008 Rapamycin treatment revealed a reduction of p-mTOR and p-4E-BP1 but increased p-AKT levels. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 46-50 18981735-7 2008 The combination of rapamycin with the MEK inhibitor U0126 significantly enhanced growth inhibitory effects of cancer cells, suggesting that MEK/ERK activation may counteract mTOR inhibitors" anticancer efficacy. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 174-178 18981735-9 2008 Moreover, the presence of erlotinib suppressed rapamycin-induced phosphorylation of Akt, ERK and eIF4E as well, implying that erlotinib can suppress mTOR inhibition-induced feedback activation of several survival signaling pathways including Akt, ERK and eIF4E. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 149-153 19180880-4 2008 Transient expressions of 3 types of mammalian target of rapamycin (mTOR), including mTOR-WT (wild type), mTOR-RR (rapamycin resistant, with kinase activity), and mTOR-RR-KD (rapamycin resistant, without kinase activity), were obtained by plasmid transfection. Sirolimus 56-65 mechanistic target of rapamycin kinase Homo sapiens 67-71 18930332-9 2008 Rapamycin inhibits phosphorylation of p70 S6 kinase and 4E-BP-1, downstream targets of mTOR, and decreases VEGF. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 87-91 18784743-2 2008 Interestingly, further inactivation of mTOR by rapamycin analog RAD001 (everolimus) significantly enhanced MS-275-mediated growth inhibition and apoptosis of these cells in parallel with enhanced upregulation of p27(kip1) and downregulation of c-Myc. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 39-43 19100909-7 2008 Mammalian TORC1 (mTORC1) is rapamycin sensitive and contains mTOR, raptor, and mLST8. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 17-21 18511708-5 2008 In a majority of tumors (67%; 10 of 15), apoptotic resistance could be reduced by more than 50% by rapamycin, an mTOR inhibitor, but not by LY294002, a PI3K inhibitor. Sirolimus 99-108 mechanistic target of rapamycin kinase Homo sapiens 113-117 18812319-2 2008 mTOR forms two functionally distinct complexes, termed the mTOR complex 1 (mTORC1) and 2 (mTORC2); only the former of which is inhibited by rapamycin. Sirolimus 140-149 mechanistic target of rapamycin kinase Homo sapiens 0-4 18812319-2 2008 mTOR forms two functionally distinct complexes, termed the mTOR complex 1 (mTORC1) and 2 (mTORC2); only the former of which is inhibited by rapamycin. Sirolimus 140-149 mechanistic target of rapamycin kinase Homo sapiens 59-63 18511708-6 2008 Responsiveness to rapamycin correlated with staining for the mTOR target, p-S6K, in the original tumor, but not for p-Akt. Sirolimus 18-27 mechanistic target of rapamycin kinase Homo sapiens 61-65 18848473-3 2008 Inhibition of mTOR by rapamycin promoted production of proinflammatory cytokines via the transcription factor NF-kappaB but blocked the release of interleukin-10 via the transcription factor STAT3. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 18790727-2 2008 We tested whether sirolimus, an immunosuppressive agent that inhibits mTOR, a protein that regulates cell division and differentiation, might modify cardiac hypertrophy after cardiac transplantation. Sirolimus 18-27 mechanistic target of rapamycin kinase Homo sapiens 70-74 18790727-8 2008 The number of cells in myocardial biopsies positive for p27Kip1, a protein induced by mTOR inhibition, increased in sirolimus-treated subjects (P = 0.0005) and did not change in controls (P = 0.54) suggesting sirolimus acted directly on myocardium. Sirolimus 116-125 mechanistic target of rapamycin kinase Homo sapiens 86-90 18713735-4 2008 We further demonstrate that DeltaPsi(m) reflects the degree of overall mammalian target of rapamycin (mTOR) activation and that the mTOR inhibitor rapamycin reduces metabolic rate, augments differentiation, and inhibits tumor formation of the mouse embryonic stem cells with a high metabolic rate. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 102-106 18682538-2 2008 To elucidate the molecular mechanism by which leucine stimulates protein synthesis in neonatal muscle, overnight-fasted 7-day-old piglets were treated with rapamycin [an inhibitor of mammalian target of rapamycin (mTOR) complex (mTORC)1] for 1 h and then infused with leucine for 1 h. Fractional rates of protein synthesis and activation of signaling components that lead to mRNA translation were determined in skeletal muscle. Sirolimus 156-165 mechanistic target of rapamycin kinase Homo sapiens 183-212 18922908-1 2008 Rapamycin (or sirolimus), the prototypical inhibitor of the mammalian target of rapamycin (mTOR) and an immunosuppressant used for the prevention of renal transplant rejection, has recently emerged as an effective treatment for Kaposi"s sarcoma (KS), an enigmatic vascular tumor and a model for pathologic angiogenesis. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 60-89 18922908-1 2008 Rapamycin (or sirolimus), the prototypical inhibitor of the mammalian target of rapamycin (mTOR) and an immunosuppressant used for the prevention of renal transplant rejection, has recently emerged as an effective treatment for Kaposi"s sarcoma (KS), an enigmatic vascular tumor and a model for pathologic angiogenesis. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 91-95 18922908-1 2008 Rapamycin (or sirolimus), the prototypical inhibitor of the mammalian target of rapamycin (mTOR) and an immunosuppressant used for the prevention of renal transplant rejection, has recently emerged as an effective treatment for Kaposi"s sarcoma (KS), an enigmatic vascular tumor and a model for pathologic angiogenesis. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 60-89 18922908-1 2008 Rapamycin (or sirolimus), the prototypical inhibitor of the mammalian target of rapamycin (mTOR) and an immunosuppressant used for the prevention of renal transplant rejection, has recently emerged as an effective treatment for Kaposi"s sarcoma (KS), an enigmatic vascular tumor and a model for pathologic angiogenesis. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 91-95 18832178-5 2008 mTORC1 activation by SF2/ASF bypasses upstream PI3K/Akt signaling and is essential for SF2/ASF-mediated transformation, as inhibition of mTOR by rapamycin blocked transformation by SF2/ASF in vitro and in vivo. Sirolimus 145-154 mechanistic target of rapamycin kinase Homo sapiens 0-4 18832563-4 2008 Infusion of PI3K inhibitors (wortmannin and LY294002) and an mTOR inhibitor (rapamycin) into the mPFC in vivo suppressed HFS-induced LTP as well as the phosphorylation of PI3K/Akt-mTOR signaling pathway. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 61-65 18832563-4 2008 Infusion of PI3K inhibitors (wortmannin and LY294002) and an mTOR inhibitor (rapamycin) into the mPFC in vivo suppressed HFS-induced LTP as well as the phosphorylation of PI3K/Akt-mTOR signaling pathway. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 180-184 18806968-5 2008 Various studies provided evidence that the macrolide rapamycin decreases growth of brain and kidney tumors by specific inhibition of mTOR kinase. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 133-137 19016759-5 2008 Cell proliferation tests in control cells demonstrated that the mTOR inhibitor rapamycin enhanced cell sensitivity to endocrine therapy when combined to OH-Tam or to fulvestrant. Sirolimus 79-88 mechanistic target of rapamycin kinase Homo sapiens 64-68 18614546-10 2008 Our data allow new insights into the molecular consequences of mTOR dysregulation under pathophysiological conditions and should help to optimize rapamycin treatment of human diseases. Sirolimus 146-155 mechanistic target of rapamycin kinase Homo sapiens 63-67 18658177-2 2008 However, a series of adverse events has been reported with the first-generation mTOR inhibitor sirolimus that includes hypersensitivity-like interstitial pneumonitis. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 80-84 18565131-9 2008 The phosphatidylinositol 3"-kinase (PI3K) inhibitor, LY294002, and the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exerted an inhibitory effect on the thrombin-induced OPG synthesis. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 102-106 18678646-6 2008 Treatment of both primary cells and cancer cell lines with rapamycin, metformin, and pyrvinium resulted in an increase in p73 levels, as did RNA interference-mediated knockdown of mTOR. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 180-184 18922461-2 2008 (2008) demonstrate that fatty acid biosynthesis, under the transcriptional control of SREBP1, is regulated by the rapamycin-sensitive mTOR signaling network, thus expanding the scope of biosynthetic processes integrated by mTOR. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 134-138 19176057-2 2008 METHODS: The expression of the downstream effector proteins of mTOR were analyzed by Western blot before and after Karpas299, BaF3/NPM-ALK and BaF3 cell lines treated with rapamycin. Sirolimus 172-181 mechanistic target of rapamycin kinase Homo sapiens 63-67 18660503-9 2008 p70 S6 kinase activation was blocked by wortmannin and rapamycin, consistent with PI3K, mTOR, and p70 S6 kinase in a linear pathway. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 88-92 18922461-2 2008 (2008) demonstrate that fatty acid biosynthesis, under the transcriptional control of SREBP1, is regulated by the rapamycin-sensitive mTOR signaling network, thus expanding the scope of biosynthetic processes integrated by mTOR. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 223-227 18769147-7 2008 Notably, rapamycin downregulated GSK-3beta Ser9 phosphorylation with concurrent nuclear export of cyclin D1 only in MCL cells in which GSK-3beta is under the control of mTOR. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 169-173 18768852-6 2008 The observed impairment of skin gammadelta T cell function is directly related to the inhibitory action of rapamycin on mammalian target of rapamycin. Sirolimus 107-116 mechanistic target of rapamycin kinase Homo sapiens 120-149 18787170-4 2008 Tumor cell lines harboring deletions or mutations in FBXW7 are particularly sensitive to rapamycin treatment, which suggests that loss of FBXW7 may be a biomarker for human cancers susceptible to treatment with inhibitors of the mTOR pathway. Sirolimus 89-98 mechanistic target of rapamycin kinase Homo sapiens 229-233 18722121-9 2008 CONCLUSIONS: We propose a unique mode of mTOR regulation in which RSK-mediated phosphorylation of Raptor regulates mTORC1 activity and thus suggest a means by which the Ras/MAPK pathway might promote rapamycin-sensitive signaling independently of the PI3K/Akt pathway. Sirolimus 200-209 mechanistic target of rapamycin kinase Homo sapiens 41-45 18588872-7 2008 Combination of honokiol with the mTOR inhibitor rapamycin presented synergistic effects on induction of apoptosis of breast cancer cells. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 33-37 18757421-0 2008 Chemoprevention and treatment of experimental Cowden"s disease by mTOR inhibition with rapamycin. Sirolimus 87-96 mechanistic target of rapamycin kinase Homo sapiens 66-70 18602894-5 2008 Rapamycin can cause hyperlipidaemia clinically, and we hypothesised that this may be mediated via an effect of mTOR on SREBP-2. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 111-115 18650261-8 2008 These increases in glucose uptake and GLUT1 levels were prevented by inhibition of mTOR with rapamycin. Sirolimus 93-102 mechanistic target of rapamycin kinase Homo sapiens 83-87 18926092-3 2008 Commercially available mTOR inhibitors include rapamycin (i.e., sirolimus) and temsirolimus. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 23-27 18926092-3 2008 Commercially available mTOR inhibitors include rapamycin (i.e., sirolimus) and temsirolimus. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 23-27 18598780-1 2008 The signalling components upstream and downstream of the protein kinase mammalian target of rapamycin (mTOR) are frequently altered in a wide variety of human diseases. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 103-107 18594209-0 2008 Combination of rapamycin and 17-allylamino-17-demethoxygeldanamycin abrogates Akt activation and potentiates mTOR blockade in breast cancer cells. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 109-113 18586400-2 2008 By using calcium imaging and patch-clamping techniques to study the role of this signaling pathway in the activity of cultured hippocampal neurons, we found that rapamycin significantly reduces the spontaneous activities of network neurons as well as the efficacy of synaptic transmission through insulin-mTOR signaling pathway. Sirolimus 162-171 mechanistic target of rapamycin kinase Homo sapiens 305-309 18547304-0 2008 The mTOR inhibitor rapamycin significantly improves facial angiofibroma lesions in a patient with tuberous sclerosis. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 18492954-3 2008 Rapamycin, an inhibitor of mTOR, enhanced IL-12 production in LPS-stimulated DCs, whereas the activation of mTOR by lentivirus-mediated transduction of a constitutively active form of Rheb suppressed the production of IL-12. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 18547304-7 2008 Immunosuppressive treatment with rapamycin, a specific mTOR inhibitor, initiated because of renal transplantation, reduced facial angiofibroma dramatically. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 55-59 18754885-1 2008 Cotylenin A, a plant growth regulator, and rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), are potent inducers of differentiation of myeloid leukemia cells. Sirolimus 43-52 mechanistic target of rapamycin kinase Homo sapiens 70-99 18754885-1 2008 Cotylenin A, a plant growth regulator, and rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), are potent inducers of differentiation of myeloid leukemia cells. Sirolimus 43-52 mechanistic target of rapamycin kinase Homo sapiens 101-105 18348264-6 2008 Carbachol-evoked S6 phosphorylation was blocked by the mTOR inhibitor rapamycin, but was independent of phosphoinositide 3-kinase activation. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 55-59 18264722-4 2008 Herein, we show that IRS-1 antisense oligonucleotide and rapamycin synergistically antagonize the activation of mTOR in vivo and induced tumor suppression, through inhibition of proliferation and induction of apoptosis, in prostate cancer cell xenografts. Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 112-116 18474542-3 2008 An in vitro study has revealed that mTOR is activated in oesophageal squamous cell carcinoma (OSCC) cell lines and that mTOR expression is inhibited by rapamycin. Sirolimus 152-161 mechanistic target of rapamycin kinase Homo sapiens 120-124 18323781-2 2008 Herein, we examined whether targeting the RAS-RAF-MEK-ERK pathway with the RAF inhibitor sorafenib and/or the PI3K-AKT-mTOR pathway with the mTOR inhibitor rapamycin has therapeutic effects against melanoma. Sirolimus 156-165 mechanistic target of rapamycin kinase Homo sapiens 141-145 18596167-4 2008 Even after macroautophagy is strongly induced by suppressing mTOR (mammalian target of rapamycin) kinase activity with rapamycin or nutrient deprivation, active cathepsin-positive autolysosomes rather than LC3-II-positive autophagosomes predominate, implying efficient autophagosome clearance in healthy neurons. Sirolimus 87-96 mechanistic target of rapamycin kinase Homo sapiens 61-65 18652687-5 2008 These profiles were further correlated with gene expression alterations caused by inhibition of PI3K/mTOR pathway with PI3K inhibitor Ly294002 or mTOR inhibitor rapamycin. Sirolimus 161-170 mechanistic target of rapamycin kinase Homo sapiens 101-105 18652687-5 2008 These profiles were further correlated with gene expression alterations caused by inhibition of PI3K/mTOR pathway with PI3K inhibitor Ly294002 or mTOR inhibitor rapamycin. Sirolimus 161-170 mechanistic target of rapamycin kinase Homo sapiens 146-150 18587045-4 2008 Mammalian target of rapamycin inhibition with sirolimus or everolimus results in attenuation of cyst formation in rat and mouse models of polycystic kidney disease. Sirolimus 46-55 mechanistic target of rapamycin kinase Homo sapiens 0-29 18715846-1 2008 Preclinical studies using human gastric adenocarcinoma (GAC) cell lines have shown that the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, can inhibit tumor growth and that the extracellular signal-regulated kinase (ERK) of the Ras/Raf kinase/ERK pathway is related to chemoresistance and apoptosis. Sirolimus 112-121 mechanistic target of rapamycin kinase Homo sapiens 123-127 18612547-7 2008 Inhibition of this pathway with the specific mTOR inhibitor, rapamycin, markedly decreased cell migration induced by formation of TF-FVIIa-FXa complex. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 45-49 18490075-7 2008 Reductions in tumor growth by bevacizumab plus rapamycin were associated with inhibition of downstream targets of the mammalian target-of-rapamycin pathway, reductions in vascular endothelial growth factor expression, and tumor microvessel density. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 118-147 18278068-6 2008 MYCN siRNA significantly blocked VEGF secretion, irrespective of serum conditions, in MYCN-amplified NB cells; this effect was enhanced when combined with rapamycin, an mTOR inhibitor. Sirolimus 155-164 mechanistic target of rapamycin kinase Homo sapiens 169-173 18675098-1 2008 Sirolimus (SRL) is an mTOR inhibitor that has been shown, in contrast to calcineurin inhibitors (CNI), to inhibit cancers in experimental models. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 22-26 18443272-14 2008 The latter was sensitive to the mTOR inhibitor, rapamycin. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 32-36 18570873-3 2008 Cellular mTOR activation, by refeeding of amino acid-deprived cells or by TSC2 shRNA, activated SGK1 and p27 phosphorylation at T157, and both were inhibited by short-term rapamycin treatment and by SGK1 shRNA. Sirolimus 172-181 mechanistic target of rapamycin kinase Homo sapiens 9-13 18283037-9 2008 The mTOR inhibitor rapamycin was found to supraadditively increase lapatinib efficacy in MCF-7/HER2 cells [ approximately 10-fold enhancement; combination index (CI(50)) = 0.243 < 1.0 = additivity, P < 0.001] but not in p70S6K1 gene-amplified MCF-7 parental cells ( approximately 1.3-fold enhancement; CI(50) = 0.920 congruent with 1.0 = additivity). Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 18250144-7 2008 Under the conditions adopted, rapamycin inhibited both mammalian target-of-rapamycin complexes (mTORC1 and mTORC2), as indicated by the reduced amount of raptor and rictor bound to mTOR in immunoprecipitates and by the marked hypophosphorylation of protein S6 kinase I (p70S6K) and Akt, determined by western blotting. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 55-84 18250144-7 2008 Under the conditions adopted, rapamycin inhibited both mammalian target-of-rapamycin complexes (mTORC1 and mTORC2), as indicated by the reduced amount of raptor and rictor bound to mTOR in immunoprecipitates and by the marked hypophosphorylation of protein S6 kinase I (p70S6K) and Akt, determined by western blotting. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 96-100 18519793-7 2008 Treatment with rapamycin resulted in inhibition of the downstream signals of the mTOR pathway and increased phosphorylation of Akt in C2 cells, whereas the constitutively activated Akt in PC3 cells was not modulated. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 81-85 18519641-7 2008 The results provide insight into the effects of Akt/mTOR-dependent signaling on gene expression and into the therapeutic action of rapamycin. Sirolimus 131-140 mechanistic target of rapamycin kinase Homo sapiens 52-56 17950843-7 2008 Under these conditions FK506, which displaces FKBP12 (to inhibit calcineurin) and rapamycin, which displaces FKBP12 (to inhibit mTOR), each increased the [Ca(2+)](c) rise evoked by caffeine. Sirolimus 82-91 mechanistic target of rapamycin kinase Homo sapiens 128-132 18282244-0 2008 Inhibition of mTOR by sirolimus induces remission of post-transplant lymphoproliferative disorders. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 18033679-11 2008 Inhibition of mTOR by rapamycin abolished the protein synthesis and cell proliferation stimulated by both IGF-1 and leucine. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 18339627-4 2008 Inhibitors of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway, particularly rapamycin, blocked much of the acquired resistance of the spheroids, suggesting a key role for mTOR. Sirolimus 72-81 mechanistic target of rapamycin kinase Homo sapiens 83-87 18630505-5 2008 Inhibition of IGF1R signaling can be accomplished by other agents, including rapamycin or temsirolimus, which target mTOR (mammalian target of rapamycin). Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 117-121 18630505-5 2008 Inhibition of IGF1R signaling can be accomplished by other agents, including rapamycin or temsirolimus, which target mTOR (mammalian target of rapamycin). Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 123-152 18483275-7 2008 Treatment with the mTOR inhibitor rapamycin effectively sensitizes established cancers to adoptive immunotherapy in vivo. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 19-23 18451215-9 2008 In contrast, although rapamycin inhibited mTOR signaling, it did not relieve phosphorylation of TSC2 at S939. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 42-46 18451215-12 2008 However, whereas rapamycin and its analogues may be efficacious at inhibiting mTOR activity, these drugs do not reverse the functional inactivation of TSC2 that occurs in these tumors. Sirolimus 17-26 mechanistic target of rapamycin kinase Homo sapiens 78-82 18375114-7 2008 Furthermore, mTOR inhibitor rapamycin not only drastically inhibited migration and MMP production, but also induced type II programmed cell death, autophagic cell death. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 13-17 18391949-2 2008 Autophagy induction with the mTOR inhibitor rapamycin accelerates clearance of these toxic substrates. Sirolimus 44-53 mechanistic target of rapamycin kinase Homo sapiens 29-33 18026138-2 2008 In this study we investigated the phosphorylation status of key proteins in the PI3K/AKT/mTOR pathway and the effects of the mTOR inhibitors rapamycin and CCI-779 on neuroblastoma tumorigenesis. Sirolimus 141-150 mechanistic target of rapamycin kinase Homo sapiens 125-129 18021293-8 2008 Treatment with rapamycin, an mTOR inhibitor, blocked Cd-induced phosphorylation of S6K1 and eukaryotic initiation factor 4E binding protein 1, and markedly inhibited Cd-induced apoptosis. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 29-33 18398477-6 2008 We then showed with electromyographic studies that the mTOR inhibitor rapamycin reduced the sensitivity of a population of myelinated nociceptors known to be important for the increased mechanical sensitivity that follows injury. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 55-59 18389497-11 2008 Correspondingly, rapamycin inhibited the abnormal activation of the mammalian target of rapamycin pathway, astrogliosis, and neuronal disorganization, and increased brain size in Tsc1(GFAP)CKO mice. Sirolimus 17-26 mechanistic target of rapamycin kinase Homo sapiens 68-97 18381446-4 2008 To determine whether mTOR is involved in 6-TG-induced autophagy, we used rapamycin, a potential anticancer agent, to inhibit mTOR activity. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 125-129 18381446-7 2008 Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser(473) and the inhibition of 6-TG-induced apoptosis and cell death. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 40-44 18174523-0 2008 mTOR inhibition by rapamycin prevents beta-cell adaptation to hyperglycemia and exacerbates the metabolic state in type 2 diabetes. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 0-4 18174523-3 2008 We tested this hypothesis in the Psammomys obesus (P. obesus) model of nutrition-dependent type 2 diabetes, using the mTOR inhibitor rapamycin. Sirolimus 133-142 mechanistic target of rapamycin kinase Homo sapiens 118-122 18261725-2 2008 Rapamycin is an inhibitor of mTOR. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 29-33 18490844-8 2008 In refed rats, PTB level in the cytoplasmic fraction returned to a level comparable to that in fed rats, but was inhibited by treatment with rapamycin, a mammalian target of rapamycin (mTOR) inhibitor. Sirolimus 141-150 mechanistic target of rapamycin kinase Homo sapiens 154-183 18490844-8 2008 In refed rats, PTB level in the cytoplasmic fraction returned to a level comparable to that in fed rats, but was inhibited by treatment with rapamycin, a mammalian target of rapamycin (mTOR) inhibitor. Sirolimus 141-150 mechanistic target of rapamycin kinase Homo sapiens 185-189 17635004-0 2008 Initial testing (stage 1) of the mTOR inhibitor rapamycin by the pediatric preclinical testing program. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 33-37 18631865-1 2008 Massive urinary protein excretion has been observed after conversion from calcineurin inhibitors to mammalian target of rapamycin (mToR) inhibitors, especially sirolimus, in renal transplant recipients with chronic allograft nephropathy. Sirolimus 160-169 mechanistic target of rapamycin kinase Homo sapiens 100-129 18631865-1 2008 Massive urinary protein excretion has been observed after conversion from calcineurin inhibitors to mammalian target of rapamycin (mToR) inhibitors, especially sirolimus, in renal transplant recipients with chronic allograft nephropathy. Sirolimus 160-169 mechanistic target of rapamycin kinase Homo sapiens 131-135 18339874-5 2008 Rapamycin repressed mTOR activity and concomitantly resulted in the activation of Akt, which could attenuate the therapeutic effects of mTOR inhibitors. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 20-24 18339874-5 2008 Rapamycin repressed mTOR activity and concomitantly resulted in the activation of Akt, which could attenuate the therapeutic effects of mTOR inhibitors. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 136-140 18320031-8 2008 It was noted that treatment of SIRT1-.transfected cells with Rapamycin, a mTOR inhibitor, reduced the phosphorylation of S6K1 and the expression of Id1, implying that SIRT1-induced phosphorylation of S6K1 may be partly for the decreased expression of p16(INK4A) and promoted phosphorylation of Rb in 2BS. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 74-78 17998426-5 2008 Interactions of mTOR with regulatory-associated protein of TOR or rapamycin-insensitive companion of mTOR result in 2 mTOR complexes, with the former (mTOR complex-1) being the primary controller of cell growth and the latter (mTOR complex-2) mediating effects that are insensitive to rapamycin, such as cytoskeletal organization. Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 16-20 18191814-4 2008 By contrast, gefitinib inhibited in a fast and completely way p-EGFR and partially p-Akt while a 3 days-rapamycin exposure resulted in the inhibition of the expression of both mTor and p70S6K. Sirolimus 104-113 mechanistic target of rapamycin kinase Homo sapiens 176-180 18075305-4 2008 Rapamycin (a specific Mtor inhibitor) could lead to G(1) arrest of many malignant cell lines, and currently analogs of rapamycin are being investigated as a cancer chemotherapeutic adjuvant. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 22-26 18075305-4 2008 Rapamycin (a specific Mtor inhibitor) could lead to G(1) arrest of many malignant cell lines, and currently analogs of rapamycin are being investigated as a cancer chemotherapeutic adjuvant. Sirolimus 119-128 mechanistic target of rapamycin kinase Homo sapiens 22-26 18075305-8 2008 These results suggest that inhibitors of mTOR may have anticancer potential when used together with some other chemotherapeutic agents, and that down-regulation of AP-1 and NF kappa B transcription activity might take part in a senescence-like growth arrest program induced by rapamycin plus 5-Fu. Sirolimus 277-286 mechanistic target of rapamycin kinase Homo sapiens 41-45 18310292-10 2008 In conclusion, rapamycin causes significant growth inhibition in carcinoid tumor cell lines in vitro and in vivo, thus mTOR is a promising therapeutic target for neuroendocrine tumors. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 119-123 18344684-0 2008 A new trick for an old drug: mTOR inhibitor rapamycin augments the effect of fluorouracil on hepatocellular carcinoma by inducing cell senescence. Sirolimus 44-53 mechanistic target of rapamycin kinase Homo sapiens 29-33 18060476-5 2008 Furthermore, rapamycin, a specific inhibitor of mTOR, blocked the activation of mTOR/p70S6K but not PI3K/Akt. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 48-52 18199797-1 2008 The immunosuppressive agent sirolimus exerts an antiproliferative effect by inhibiting mammalian target of rapamycin (mTOR). Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 87-116 18199797-1 2008 The immunosuppressive agent sirolimus exerts an antiproliferative effect by inhibiting mammalian target of rapamycin (mTOR). Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 118-122 18199797-8 2008 In summary, treatment with sirolimus was associated with decreased polycystic liver volume, perhaps by preventing aberrant activation of mTOR in epithelial cells lining the cysts. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 137-141 18060476-5 2008 Furthermore, rapamycin, a specific inhibitor of mTOR, blocked the activation of mTOR/p70S6K but not PI3K/Akt. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 80-84 18374093-6 2008 Rapamycin treatment of islets resulted in reduced phosphorylation of p70s6k, a downstream effector molecule of mTOR and increased ERK1/2 phosphorylation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 111-115 17700525-9 2008 Importantly, this study provides evidence indicating that tumors with defective TGF-beta signaling--common in colon and pancreatic cancers--will be selectively sensitive to rapamycin or other strategies that target mTOR. Sirolimus 173-182 mechanistic target of rapamycin kinase Homo sapiens 215-219 18250445-6 2008 Long-term pretreatment with the mTOR inhibitor rapamycin significantly blocked both mTOR-raptor and mTOR-rictor complex formation. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 32-36 18250445-6 2008 Long-term pretreatment with the mTOR inhibitor rapamycin significantly blocked both mTOR-raptor and mTOR-rictor complex formation. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 84-88 18250445-6 2008 Long-term pretreatment with the mTOR inhibitor rapamycin significantly blocked both mTOR-raptor and mTOR-rictor complex formation. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 84-88 17719815-8 2008 The IGFBP-3-promoted apoptosis in the presence of IFN-gamma could also be abrogated by blockade of the mTOR pathway with its pharmacological inhibitors, LY294002 or rapamycin. Sirolimus 165-174 mechanistic target of rapamycin kinase Homo sapiens 103-107 18068336-6 2008 mTOR inhibitor rapamycin and a dominant negative mutant of mTOR suppressed TGFbeta-induced phosphorylation of S6 kinase and 4EBP-1. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 0-4 18039669-9 2008 In addition, rapamycin inhibited leptin-induced adipose differentiation-related protein accumulation in macrophages and lipid body-dependent leukotriene synthesis, demonstrating a key role for mTOR in lipid body biogenesis and function. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 193-197 18307022-0 2008 Effects of the mTOR inhibitor sirolimus in patients with hepatocellular and cholangiocellular cancer. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 15-19 18305058-2 2008 Currently, the mTOR inhibitor rapamycin and its analogues (CCI-779, RAD001, AP23573), which induce cell-cycle arrest in the G(1) phase, are being evaluated in cancer clinical trials. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 15-19 17921520-2 2008 Aggregate-prone proteins are cleared by macroautophagy, and upregulating this process by rapamycin, which inhibits the mammalian target of rapamycin (mTOR), attenuates their toxicity in various HD models. Sirolimus 89-98 mechanistic target of rapamycin kinase Homo sapiens 119-148 17921520-2 2008 Aggregate-prone proteins are cleared by macroautophagy, and upregulating this process by rapamycin, which inhibits the mammalian target of rapamycin (mTOR), attenuates their toxicity in various HD models. Sirolimus 89-98 mechanistic target of rapamycin kinase Homo sapiens 150-154 17921520-6 2008 In order to counteract the autophagy inhibitory effects of mTOR activation resulting from lithium treatment, we have used the mTOR inhibitor rapamycin in combination with lithium. Sirolimus 141-150 mechanistic target of rapamycin kinase Homo sapiens 59-63 17921520-6 2008 In order to counteract the autophagy inhibitory effects of mTOR activation resulting from lithium treatment, we have used the mTOR inhibitor rapamycin in combination with lithium. Sirolimus 141-150 mechanistic target of rapamycin kinase Homo sapiens 126-130 17942753-6 2008 Pim 2-deficient B cells are readily protected from death by BLyS stimulation, but this protection is completely abrogated by treatment with the mTOR inhibitor rapamycin. Sirolimus 159-168 mechanistic target of rapamycin kinase Homo sapiens 144-148 18184959-2 2008 The drug sirolimus suppresses mTOR signaling. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 30-34 17993646-4 2008 Here we show that rapamycin, the inhibitor of mTOR signaling, rescues insulin signaling and glycogen synthesis from IL-6 inhibition in HepG2 hepatocarcinoma cells as well as in mouse primary hepatocytes. Sirolimus 18-27 mechanistic target of rapamycin kinase Homo sapiens 46-50 18370442-1 2008 Temsirolimus, an ester of sirolimus (rapamycin), selectively inhibits the kinase mammalian target of rapamycin and consequently blocks the translation of cell cycle regulatory proteins and prevents the over expression of angiogenic growth factors. Sirolimus 3-12 mechanistic target of rapamycin kinase Homo sapiens 81-110 18209481-6 2008 Rapamycin and dibutyryl-cAMP, which inhibited basal signaling via mammalian target of rapamycin (mTOR), restored insulin-induced PKB- but not IRbeta phosphorylation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 66-95 18209481-6 2008 Rapamycin and dibutyryl-cAMP, which inhibited basal signaling via mammalian target of rapamycin (mTOR), restored insulin-induced PKB- but not IRbeta phosphorylation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 97-101 18980674-1 2008 INTRODUCTION: Treatment with sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to be efficacious in the MRL/lpr and NZB x NZW F1 mouse models of lupus nephritis, indicating a critical role for the mTOR pathway in both models. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 42-71 18980674-1 2008 INTRODUCTION: Treatment with sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to be efficacious in the MRL/lpr and NZB x NZW F1 mouse models of lupus nephritis, indicating a critical role for the mTOR pathway in both models. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 73-77 17955327-5 2008 Pre-treatment of cardiocytes with the mTOR inhibitor rapamycin blocked the agonist-induced rpL32 mRNA mobilization to polysomes. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 38-42 18370442-1 2008 Temsirolimus, an ester of sirolimus (rapamycin), selectively inhibits the kinase mammalian target of rapamycin and consequently blocks the translation of cell cycle regulatory proteins and prevents the over expression of angiogenic growth factors. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 81-110 17908691-3 2007 We have previously reported that rapamycin promotes VSMC differentiation by inhibiting the mammalian target of rapamycin (mTOR) target S6K1. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 91-120 18776537-20 2008 The latter is a downstream kinase of rapamycin and its phosphorylation is inhibited by rapamycin, an mTOR inhibitor. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 101-105 18094094-7 2008 The observation that the TSC1/TSC2 functions as a negative regulator of the mammalian target of rapamycin (mTOR)/p70 S6 kinase (S6K1) signaling pathway yielded the first rapamycin clinical trial for LAM. Sirolimus 96-105 mechanistic target of rapamycin kinase Homo sapiens 107-111 18509482-1 2008 A 66-year old female with HIV-negative classic Kaposi"s sarcoma responded to mTOR targeting by rapamycin. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 77-81 17908691-3 2007 We have previously reported that rapamycin promotes VSMC differentiation by inhibiting the mammalian target of rapamycin (mTOR) target S6K1. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 122-126 17347776-0 2007 Decreased levels of hypoxic cells in gefitinib treated ER+ HER-2 overexpressing MCF-7 breast cancer tumors are associated with hyperactivation of the mTOR pathway: therapeutic implications for combination therapy with rapamycin. Sirolimus 218-227 mechanistic target of rapamycin kinase Homo sapiens 150-154 17983731-1 2007 PURPOSE: We assayed the effects of rapamycin, an immunomodulatory agent known to inhibit the activity of the mammalian target of rapamycin (mTOR) cascade, on candidate gene expression and single unit firing properties in cultured rat hippocampal neurons as a strategy to define the effects of rapamycin on neuronal gene transcription and excitability. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 140-144 17713840-3 2007 Rapamycin and its analogs temsirolimus and everolimus are specific inhibitors of mTOR that exert suppressive effects on proliferation, invasion, and metastasis and induce apoptosis of tumor cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 81-85 18082048-1 2007 OBJECTIVE: This study examined the effect of rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), on eukaryotic initiation factor (eIF- 4E) expression in rat myocardial fibroblasts infected by Coxsackievirus B3 (CVB3) in order to identify the drug target for treatment of viral myocarditis. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 72-101 18082048-1 2007 OBJECTIVE: This study examined the effect of rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), on eukaryotic initiation factor (eIF- 4E) expression in rat myocardial fibroblasts infected by Coxsackievirus B3 (CVB3) in order to identify the drug target for treatment of viral myocarditis. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 103-107 18046414-5 2007 In skeletal muscle tissues and cells, the mTOR inhibitor rapamycin decreased the gene expression of the mitochondrial transcriptional regulators PGC-1alpha, oestrogen-related receptor alpha and nuclear respiratory factors, resulting in a decrease in mitochondrial gene expression and oxygen consumption. Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 42-46 17986349-3 2007 Rapamycin (also known as sirolimus), an mTOR inhibitor, has been shown to reduce disease severity in rodent models of TSC and is currently being evaluated in clinical trials in human populations. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 40-44 17986349-3 2007 Rapamycin (also known as sirolimus), an mTOR inhibitor, has been shown to reduce disease severity in rodent models of TSC and is currently being evaluated in clinical trials in human populations. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 40-44 17968710-5 2007 Sirolimus is effective in vivo against pancreatic carcinoma and demonstrates that the effect of sirolimus on the inhibition of tumor cell proliferation is associated with the suppression of the mTOR/HIF-1alpha/vascular endothelial growth factor (VEGF) pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 194-198 17968710-5 2007 Sirolimus is effective in vivo against pancreatic carcinoma and demonstrates that the effect of sirolimus on the inhibition of tumor cell proliferation is associated with the suppression of the mTOR/HIF-1alpha/vascular endothelial growth factor (VEGF) pathway. Sirolimus 96-105 mechanistic target of rapamycin kinase Homo sapiens 194-198 17950100-3 2007 To determine if signaling via mTOR might be directly involved in regulation of fatty acid metabolism in hepatocytes, we performed studies with rapamycin, a specific inhibitor of mTOR. Sirolimus 143-152 mechanistic target of rapamycin kinase Homo sapiens 30-34 17950100-3 2007 To determine if signaling via mTOR might be directly involved in regulation of fatty acid metabolism in hepatocytes, we performed studies with rapamycin, a specific inhibitor of mTOR. Sirolimus 143-152 mechanistic target of rapamycin kinase Homo sapiens 178-182 17664276-6 2007 The insulin resistance of the of the PTP-1B-/- adipocytes could also be rescued by treatment with rapamycin, suggesting that in adipose the loss of PTP-1B results in basal activation of mTOR (mammalian target of rapamycin) complex 1 leading to a tissue-specific insulin resistance. Sirolimus 98-107 mechanistic target of rapamycin kinase Homo sapiens 186-190 17664276-6 2007 The insulin resistance of the of the PTP-1B-/- adipocytes could also be rescued by treatment with rapamycin, suggesting that in adipose the loss of PTP-1B results in basal activation of mTOR (mammalian target of rapamycin) complex 1 leading to a tissue-specific insulin resistance. Sirolimus 98-107 mechanistic target of rapamycin kinase Homo sapiens 192-221 17825298-2 2007 Rapamycin is considered to be a highly specific inhibitor of the protein kinase mTOR; however, mTOR is also considered to be a PI3K-dependent signaling molecule. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 80-84 17845575-1 2007 The mammalian-target-of-rapamycin/mTOR-inhibitor sirolimus as a component of the immunosuppressive strategy after solid organ transplantation is effective at preventing allograft rejection. Sirolimus 49-58 mechanistic target of rapamycin kinase Homo sapiens 4-33 17845575-1 2007 The mammalian-target-of-rapamycin/mTOR-inhibitor sirolimus as a component of the immunosuppressive strategy after solid organ transplantation is effective at preventing allograft rejection. Sirolimus 49-58 mechanistic target of rapamycin kinase Homo sapiens 34-38 17728765-2 2007 Although sirolimus (rapamycin), the oldest inhibitor of mTOR, was discovered more than 30 years ago, renewed interest in this pathway is evident by the numerous rapalogs recently developed. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 56-60 17728765-2 2007 Although sirolimus (rapamycin), the oldest inhibitor of mTOR, was discovered more than 30 years ago, renewed interest in this pathway is evident by the numerous rapalogs recently developed. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 56-60 17724683-7 2007 Similarly, functional responses to LPS are partially wortmannin resistant yet sensitive to mTOR inhibition by rapamycin. Sirolimus 110-119 mechanistic target of rapamycin kinase Homo sapiens 91-95 17804674-2 2007 Our aim was to evaluate the effect of sirolimus, an mTOR inhibitor, on renal function and histology in a proteinuric model of reduced renal mass. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 52-56 17670836-9 2007 On the other hand, rapamycin, an mTOR inhibitor, significantly suppressed VSV replication in GADD34-KO MEFs. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 33-37 17624310-5 2007 In addition, D-glucosamine enhanced the growth inhibitory effects of rapamycin, a specific inhibitor of mTOR. Sirolimus 69-78 mechanistic target of rapamycin kinase Homo sapiens 104-108 17983731-1 2007 PURPOSE: We assayed the effects of rapamycin, an immunomodulatory agent known to inhibit the activity of the mammalian target of rapamycin (mTOR) cascade, on candidate gene expression and single unit firing properties in cultured rat hippocampal neurons as a strategy to define the effects of rapamycin on neuronal gene transcription and excitability. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 109-138 17698027-6 2007 Experiments using chimeric apoB UTR-luciferase constructs transfected into HepG2 cells followed by treatment with wortmannin, a PI-3K inhibitor, and rapamycin, an mTOR inhibitor, showed that signaling via PI-3K and mTOR pathways is necessary for insulin-mediated inhibition of chimeric 5" UTR-luciferase expression. Sirolimus 149-158 mechanistic target of rapamycin kinase Homo sapiens 163-167 17698027-6 2007 Experiments using chimeric apoB UTR-luciferase constructs transfected into HepG2 cells followed by treatment with wortmannin, a PI-3K inhibitor, and rapamycin, an mTOR inhibitor, showed that signaling via PI-3K and mTOR pathways is necessary for insulin-mediated inhibition of chimeric 5" UTR-luciferase expression. Sirolimus 149-158 mechanistic target of rapamycin kinase Homo sapiens 215-219 17868472-2 2007 Evidence has recently been obtained from animal experiments that activation of the mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cyst growth and renal volume expansion, and that the inhibition of mTOR with rapamycin (sirolimus) markedly slows cyst development and renal functional deterioration. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 114-118 17868472-2 2007 Evidence has recently been obtained from animal experiments that activation of the mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cyst growth and renal volume expansion, and that the inhibition of mTOR with rapamycin (sirolimus) markedly slows cyst development and renal functional deterioration. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 229-233 17868472-2 2007 Evidence has recently been obtained from animal experiments that activation of the mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cyst growth and renal volume expansion, and that the inhibition of mTOR with rapamycin (sirolimus) markedly slows cyst development and renal functional deterioration. Sirolimus 250-259 mechanistic target of rapamycin kinase Homo sapiens 83-112 17868472-2 2007 Evidence has recently been obtained from animal experiments that activation of the mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cyst growth and renal volume expansion, and that the inhibition of mTOR with rapamycin (sirolimus) markedly slows cyst development and renal functional deterioration. Sirolimus 250-259 mechanistic target of rapamycin kinase Homo sapiens 114-118 17868472-2 2007 Evidence has recently been obtained from animal experiments that activation of the mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cyst growth and renal volume expansion, and that the inhibition of mTOR with rapamycin (sirolimus) markedly slows cyst development and renal functional deterioration. Sirolimus 250-259 mechanistic target of rapamycin kinase Homo sapiens 229-233 17868472-4 2007 METHOD/DESIGN: This single center, randomised controlled, open label trial assesses the therapeutic effect, safety and tolerability of the mTOR inhibitor sirolimus (Rapamune) in patients with autosomal dominant polycystic kidney disease and preserved renal function. Sirolimus 154-163 mechanistic target of rapamycin kinase Homo sapiens 139-143 17390104-0 2007 Specific mTOR inhibitor rapamycin enhances cytotoxicity induced by alkylating agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) in human U251 malignant glioma cells. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 9-13 17575014-8 2007 Inhibition of the mammalian target of rapamycin (mTOR) pathway by rapamycin not only inhibited the phosphorylation of p70(S6K) and the expression of cell cycle regulatory proteins but also reduced accumulation of > or =4N cells and BrdU incorporation of >4N cells. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 49-53 17390104-2 2007 Rapamycin is a highly specific inhibitor of mTOR and induces a cytostatic effect in various glioma cell lines. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 44-48 17609269-5 2007 This suppression of HBV gene transcription was apparently mediated by the activation of mTOR, as it was abolished by the mTOR inhibitor rapamycin. Sirolimus 136-145 mechanistic target of rapamycin kinase Homo sapiens 88-92 17609269-5 2007 This suppression of HBV gene transcription was apparently mediated by the activation of mTOR, as it was abolished by the mTOR inhibitor rapamycin. Sirolimus 136-145 mechanistic target of rapamycin kinase Homo sapiens 121-125 17890266-7 2007 This overview provides a summary of the current literature on inhibitors of the mammalian target of rapamycin, with a special focus on sirolimus. Sirolimus 135-144 mechanistic target of rapamycin kinase Homo sapiens 80-109 17970580-0 2007 [3/3 Inhibitors of mTOR (sirolimus and everolimus)]. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 19-23 17353907-8 2007 Finally, the mTOR inhibitor rapamycin markedly decreased proliferation and increased the apoptotic rate of ALK+TCL cells. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 13-17 17889116-5 2007 An mTOR inhibitor was introduced to replace cyclosporine (everolimus, 65%; sirolimus, 35%). Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 3-7 17968710-0 2007 Sirolimus inhibits human pancreatic carcinoma cell proliferation by a mechanism linked to the targeting of mTOR/HIF-1 alpha/VEGF signaling. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 107-111 17968710-1 2007 Sirolimus(SRL, Rapamune(a), rapamycin) is a highly specific inhibitor of mammalian target of rapamycin (mTOR). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 73-102 17968710-1 2007 Sirolimus(SRL, Rapamune(a), rapamycin) is a highly specific inhibitor of mammalian target of rapamycin (mTOR). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 104-108 17968710-2 2007 Sirolimus exerts its biological activity by inhibiting the serine-threonine kinase mammalian target of rapamycin (mTOR), which regulates important cellular processes such as control of cell cycle, cell size, translation initiation and transcription. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 83-112 17968710-2 2007 Sirolimus exerts its biological activity by inhibiting the serine-threonine kinase mammalian target of rapamycin (mTOR), which regulates important cellular processes such as control of cell cycle, cell size, translation initiation and transcription. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 114-118 17968710-3 2007 The ability of sirolimus to inhibit cancer cell proliferation has led to efforts to develop rapamycin and related mTOR inhibitors as anticancer agents. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 114-118 17553806-3 2007 In these studies we treated endothelial cells with the mTOR inhibitor rapamycin, and we found that it decreases Akt phosphorylation and activity, as determined by phosphorylation of its substrate glycogen synthase kinase-3. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 55-59 17553806-5 2007 Also, in the presence of rapamycin, vascular endothelial growth factor, tumor necrosis factor, and insulin failed to phosphorylate Akt, further indicating that mTOR regulates Akt activation in endothelial cells. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 160-164 17645716-1 2007 The mTOR (mammalian target of rapamycin) inhibitors sirolimus (SRL) and everolimus (EVL) are potent immunosuppressive agents, which allow reducing the dose of the nephrotoxic calcineurin inhibitors cyclosporin and tacrolimus (TAC) in solid organ transplant recipients. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 4-8 17494629-6 2007 S6K deletion in muscle mimics the effect of the mTOR inhibitor rapamycin on rpS6 and eIF4B phosphorylation without affecting eEF2 phosphorylation. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 48-52 17510244-2 2007 Inhibiting mTOR activation using rapamycin significantly reduced the FSH-mediated increase in cyclin D2 mRNA expression, suggesting that mTOR plays a role in the FSH-mediated increase in granulosa cell proliferation. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 11-15 17510244-2 2007 Inhibiting mTOR activation using rapamycin significantly reduced the FSH-mediated increase in cyclin D2 mRNA expression, suggesting that mTOR plays a role in the FSH-mediated increase in granulosa cell proliferation. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 137-141 17634255-3 2007 Hearts from male Sprague-Dawley rats fed a meal consisting of rat nonpurified diet were sampled prior to and 3 h following the meal in the presence or absence of treatment with rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR) complex 1. Sirolimus 177-186 mechanistic target of rapamycin kinase Homo sapiens 208-237 17766661-3 2007 Currently, the mTOR inhibitor rapamycin and its derivatives CCI-779, RAD001, and AP23573 are being evaluated in cancer clinical trials. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 15-19 17646396-5 2007 Rapamycin, a specific inhibitor of mTOR complex 1, inhibits the TGF-beta-induced translation pathway and increase in cell size without affecting the EMT phenotype. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 35-39 17646396-8 2007 Activation of mTOR by TGF-beta, which leads to increased cell size and invasion, adds to the role of TGF-beta-induced EMT in cancer progression and may represent a therapeutic opportunity for rapamycin analogues in cancer. Sirolimus 192-201 mechanistic target of rapamycin kinase Homo sapiens 14-18 17502379-4 2007 Our work shows that activation of mTOR by Ras homologue enriched in brain (Rheb) overexpression potently enhances the activity of HIF1alpha and vascular endothelial growth factor (VEGF)-A secretion during hypoxia, which is reversed with rapamycin. Sirolimus 237-246 mechanistic target of rapamycin kinase Homo sapiens 34-38 17502379-10 2007 Our work explains why human cancers with aberrant mTOR signaling are prone to angiogenesis and suggests that inhibition of mTOR with rapamycin might be a suitable therapeutic strategy. Sirolimus 133-142 mechanistic target of rapamycin kinase Homo sapiens 50-54 17502379-10 2007 Our work explains why human cancers with aberrant mTOR signaling are prone to angiogenesis and suggests that inhibition of mTOR with rapamycin might be a suitable therapeutic strategy. Sirolimus 133-142 mechanistic target of rapamycin kinase Homo sapiens 123-127 17389711-3 2007 Gastrocnemius from male Sprague-Dawley rats trained to consume a meal consisting of rat chow was sampled prior to and following 3 h of having the meal provided in the presence or absence of treatment with rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR) complex 1 (TORC1). Sirolimus 205-214 mechanistic target of rapamycin kinase Homo sapiens 236-265 17004104-11 2007 Rapamycin, an inhibitor of MTOR, was synergistic with fluvastatin in two of the four cell lines and antagonistic in two other cell lines. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 17623090-11 2007 Combined treatment with AICAR and the mTOR inhibitor rapamycin resulted in additive anti-proliferative activity ALL cells. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 38-42 17645716-1 2007 The mTOR (mammalian target of rapamycin) inhibitors sirolimus (SRL) and everolimus (EVL) are potent immunosuppressive agents, which allow reducing the dose of the nephrotoxic calcineurin inhibitors cyclosporin and tacrolimus (TAC) in solid organ transplant recipients. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 10-39 17394554-7 2007 In parallel, it was found that the NA-induced increase in MCT2 protein was almost completely blocked by LY294002 (phosphoinositide 3-kinase inhibitor) as well as by rapamycin (mTOR inhibitor), while mitogen-activated protein kinase kinase and p38 MAPK inhibitors had much smaller effects. Sirolimus 165-174 mechanistic target of rapamycin kinase Homo sapiens 176-180 17549403-4 2007 IGF-I induction of myogenin protein was blocked by anti-IGF-IR monoclonal antibody alphaIR-3 and the mTOR-specific inhibitor rapamycin. Sirolimus 125-134 mechanistic target of rapamycin kinase Homo sapiens 101-105 17549426-3 2007 In this study, we have analyzed the molecular impact on a human leiomyosarcoma cell line (SK-LMS-1) of a combination consisting of the mTOR inhibitor rapamycin and either the anti-metabolite drug gemcitabine (Gemzar) or the protein tyrosine kinase inhibitor imatinib mesylate (Gleevec, STI571). Sirolimus 150-159 mechanistic target of rapamycin kinase Homo sapiens 135-139 17379645-6 2007 Short-term treatment with rapamycin, an mTOR (mammalian target of rapamycin) inhibitor, completely abrogated the ability of insulin to increase the rate and magnitude of Ca2+ signaling and production of inositol 1,4,5-trisphosphate in response to bradykinin stimulation, indicating that insulin potentiates Gq protein-coupled receptor signaling through an mTOR-dependent pathway. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 40-44 17379645-6 2007 Short-term treatment with rapamycin, an mTOR (mammalian target of rapamycin) inhibitor, completely abrogated the ability of insulin to increase the rate and magnitude of Ca2+ signaling and production of inositol 1,4,5-trisphosphate in response to bradykinin stimulation, indicating that insulin potentiates Gq protein-coupled receptor signaling through an mTOR-dependent pathway. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 46-75 17379645-6 2007 Short-term treatment with rapamycin, an mTOR (mammalian target of rapamycin) inhibitor, completely abrogated the ability of insulin to increase the rate and magnitude of Ca2+ signaling and production of inositol 1,4,5-trisphosphate in response to bradykinin stimulation, indicating that insulin potentiates Gq protein-coupled receptor signaling through an mTOR-dependent pathway. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 356-360 17463046-7 2007 We further demonstrate that placental mTOR regulates activity of the l-amino acid transporter, but not system A or taurine transporters, by determining the mediated uptake of isotope-labelled leucine, methylaminoisobutyric acid and taurine in primary villous fragments after inhibition of mTOR using rapamycin. Sirolimus 300-309 mechanistic target of rapamycin kinase Homo sapiens 38-42 17466941-5 2007 Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), suppressed leucine-induced activation of p70 S6 kinase and 4E-BP1 and negated the stimulatory effect of leucine on HGF production. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-56 17692667-4 2007 Everolimus is an mTOR inhibitor sirolimus analogue, that has proved, to be highly efficacious to prevent acute myocardial rejection and reduce the severity of cardiac allograft vasculopathy in de novo HTx patients. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 17-21 17466941-5 2007 Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), suppressed leucine-induced activation of p70 S6 kinase and 4E-BP1 and negated the stimulatory effect of leucine on HGF production. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 58-62 17329620-11 2007 Rapamycin partially inhibited this increase in mTOR-mediated S6K phosphorylation and IRS-1 Ser312 and Ser636 phosphorylation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 47-51 17397797-2 2007 Here we show that also rapamycin, an inhibitor of mTOR kinase, stimulates system y(+)-mediated arginine uptake in human endothelial cells derived from either saphenous (HSVECs) or umbilical veins (HUVECs). Sirolimus 23-32 mechanistic target of rapamycin kinase Homo sapiens 50-54 17452018-2 2007 mTOR exists in two complexes: mTOR Complex1, which is rapamycin-sensitive and phosphorylates S6K1 and initiation factor 4E binding proteins (4E-BPs), and mTOR Complex2, which is rapamycin-insensitive and phosphorylates protein kinase B (PKB, also known as Akt). Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 0-4 17543777-4 2007 Everolimus and sirolimus, the proliferation signal inhibitors (PSIs) or mammalian target-of-rapamycin (mTOR) inhibitors, now provide new strategies for immunosuppression because of their proven efficacy that translates to a reduction in doses of calcineurin inhibitors needed to prevent acute rejection. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 72-101 17543777-4 2007 Everolimus and sirolimus, the proliferation signal inhibitors (PSIs) or mammalian target-of-rapamycin (mTOR) inhibitors, now provide new strategies for immunosuppression because of their proven efficacy that translates to a reduction in doses of calcineurin inhibitors needed to prevent acute rejection. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 103-107 17371807-8 2007 The mTOR inhibitor, rapamycin, also inhibited entry into S phase. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 4-8 17452018-2 2007 mTOR exists in two complexes: mTOR Complex1, which is rapamycin-sensitive and phosphorylates S6K1 and initiation factor 4E binding proteins (4E-BPs), and mTOR Complex2, which is rapamycin-insensitive and phosphorylates protein kinase B (PKB, also known as Akt). Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 30-34 17452018-2 2007 mTOR exists in two complexes: mTOR Complex1, which is rapamycin-sensitive and phosphorylates S6K1 and initiation factor 4E binding proteins (4E-BPs), and mTOR Complex2, which is rapamycin-insensitive and phosphorylates protein kinase B (PKB, also known as Akt). Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 30-34 17483347-6 2007 An inhibitor of mTOR, rapamycin, was able to revert this phenotype. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 16-20 17350953-1 2007 Rapamycin is an immunosuppressive drug that binds simultaneously to the 12-kDa FK506- and rapamycin-binding protein (FKBP12, or FKBP) and the FKBP-rapamycin binding (FRB) domain of the mammalian target of rapamycin (mTOR) kinase. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 185-214 17350953-1 2007 Rapamycin is an immunosuppressive drug that binds simultaneously to the 12-kDa FK506- and rapamycin-binding protein (FKBP12, or FKBP) and the FKBP-rapamycin binding (FRB) domain of the mammalian target of rapamycin (mTOR) kinase. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 216-220 20477684-1 2007 The mammalian target of rapamycin (mTOR) inhibitor drugs rapamycin (sirolimus) and everolimus have undergone extensive clinical trials for a variety of organ grafts and have been licensed for use in human transplantation. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 35-39 20477684-1 2007 The mammalian target of rapamycin (mTOR) inhibitor drugs rapamycin (sirolimus) and everolimus have undergone extensive clinical trials for a variety of organ grafts and have been licensed for use in human transplantation. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 4-33 20477684-1 2007 The mammalian target of rapamycin (mTOR) inhibitor drugs rapamycin (sirolimus) and everolimus have undergone extensive clinical trials for a variety of organ grafts and have been licensed for use in human transplantation. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 35-39 17016437-6 2007 Assessment of p70S6 kinase activity indicated that rapamycin induced comparable mTOR inhibition in both cell lines suggesting that an adverse effect on VEGF cap-dependent translation would be comparable. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 80-84 17007924-0 2007 Longitudinal inhibition of PI3K/Akt/mTOR signaling by LY294002 and rapamycin induces growth arrest of adult T-cell leukemia cells. Sirolimus 67-76 mechanistic target of rapamycin kinase Homo sapiens 36-40 17007924-2 2007 Rapamycin (1-100 nM, 48h), the inhibitor of mTOR and its analog RAD001 (1-100 nM, 48 h)-induced growth inhibition and G0/G1 cell cycle arrest of these cells in association with de-phosphorylation of p70S6K and 4E-BP-1, although IC50 was not achieved. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 44-48 17483438-5 2007 Rapamycin, a selective inhibitor of mTOR, reduced VEGF production in rhabdomyosarcoma cells under normoxic conditions and partially suppressed hypoxia-driven increases in VEGF. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 36-40 17482291-4 2007 Wortmannin, SH-5, and rapamycin significantly blocked PDGF-stimulated induction of SphK1 mRNA and protein expression, indicating a regulatory role of the PI3K/AKT/mTOR pathway in SphK1 expression. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 163-167 17158029-5 2007 The mTOR inhibitor rapamycin mitigated apoptosis in U266 but potentiated it in H929 cells. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 17299523-2 2007 Therefore, we investigated whether the mTOR inhibitor rapamycin, besides its known antihemangiogenic effect, also impedes regenerative lymphangiogenesis. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 39-43 17301289-6 2007 Although Akt did not require mTOR/RAPTOR to maintain surface Glut1 levels, inhibition of mTOR/RAPTOR by rapamycin greatly diminished glucose uptake, suggesting Akt-stimulated mTOR/RAPTOR may promote Glut1 transporter activity. Sirolimus 104-113 mechanistic target of rapamycin kinase Homo sapiens 89-93 17301289-6 2007 Although Akt did not require mTOR/RAPTOR to maintain surface Glut1 levels, inhibition of mTOR/RAPTOR by rapamycin greatly diminished glucose uptake, suggesting Akt-stimulated mTOR/RAPTOR may promote Glut1 transporter activity. Sirolimus 104-113 mechanistic target of rapamycin kinase Homo sapiens 89-93 17445551-3 2007 Nevertheless, increasing data have demonstrated that sirolimus (SRL), the first mTOR introduced in the treatment of solid organ transplant recipients, induces proteinuria, an adverse event that could produce deterioration of long-term renal function. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 80-84 17371596-6 2007 Incubation of rapamycin (inhibitor of mTOR) inhibited amino acid or insulin-dependent p70 S6 kinase phosphorylation, blocked (P < 0.05) the inhibitory effects of 1.0 x PC AA on protein degradation, but did not alter the inhibitory effects of insulin or leucine CONCLUSION: In a C2C12 myotube model of myofibrillar protein turnover, amino acid limitation increases proteolysis in a ubiquitin-proteasome-dependent manner. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 38-42 17336708-2 2007 The present study is designed to explore mTOR signaling in peripheral-blood mononuclear cells (PBMCs) from renal transplant recipients with Kaposi sarcoma and ascertain whether it would reflect deregulation of the AKT-mTOR pathway in skin cancer tissue and might help identify which patients would benefit from rapamycin treatment, as well as to monitor their clinical response. Sirolimus 311-320 mechanistic target of rapamycin kinase Homo sapiens 41-45 17336708-7 2007 Thus, monitoring P70(S6K) phosphorylation can help predict and monitor the biological effectiveness of rapamycin in renal transplant recipients with Kaposi sarcoma and possibly adjust the biologically active doses of the mTOR inhibitor. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 221-225 17082322-1 2007 The antitumor potency of the mTOR inhibitor rapamycin (sirolimus) is the subject of intense investigations. Sirolimus 44-53 mechanistic target of rapamycin kinase Homo sapiens 29-33 17179228-2 2007 We investigated the molecular effects of mTOR inhibition by the rapamycin derivatives (RDs) temsirolimus (CCI-779) and everolimus (RAD001) in acute myeloid leukemia (AML) cells. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 41-45 17082322-1 2007 The antitumor potency of the mTOR inhibitor rapamycin (sirolimus) is the subject of intense investigations. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 29-33 17360675-10 2007 In mammalian systems, we find that mammalian target of rapamycin (mTOR) carrying analogous mutations (L1460P or E2419K), although sensitive to rapamycin, exhibits constitutive activation even when the cells are starved for nutrients. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 66-70 17109887-4 2007 The sensitivity of these cells to rapamycin has been attributed to activation of the PI3K/Akt/mTOR pathway by nongenomic ER signaling. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 94-98 17109887-10 2007 In our system, this sensitivity is probably not due to nongenomic ER activation of the PI3K/Akt/mTOR pathway; rapid stimulation of mTOR occurred nonspecifically after medium replacement, and addition of E2 stimulated mTOR only after 1 h. Combining rapamycin and tamoxifen under E2-dependent conditions yielded additive/synergistic effects at effective concentrations. Sirolimus 248-257 mechanistic target of rapamycin kinase Homo sapiens 131-135 17109887-10 2007 In our system, this sensitivity is probably not due to nongenomic ER activation of the PI3K/Akt/mTOR pathway; rapid stimulation of mTOR occurred nonspecifically after medium replacement, and addition of E2 stimulated mTOR only after 1 h. Combining rapamycin and tamoxifen under E2-dependent conditions yielded additive/synergistic effects at effective concentrations. Sirolimus 248-257 mechanistic target of rapamycin kinase Homo sapiens 131-135 17318075-9 2007 Prospective clinical trials are needed to test whether the activation status of the mTOR pathway in HCCs predicts the antitumor effect of rapamycin derivative in the posttransplantation course. Sirolimus 138-147 mechanistic target of rapamycin kinase Homo sapiens 84-88 17182613-5 2007 Furthermore, trehalose and mTOR inhibition by rapamycin together exerted an additive effect on the clearance of these aggregate-prone proteins because of increased autophagic activity. Sirolimus 46-55 mechanistic target of rapamycin kinase Homo sapiens 27-31 17329974-6 2007 Indeed, pharmacological inhibition of mTOR with rapamycin has shown promising results in preventing vGPCR tumorigenesis in an animal model for KS. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 38-42 17108021-4 2007 mTOR is a regulator of cell growth and metabolism downstream of Akt and is specifically inhibited by rapamycin. Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 0-4 17316544-7 2007 The effects of sirolimus (most often studied mTOR inhibitor) appear to depend on serum levels, cell type (ss cell or cell line), species (human or animal) and also environmental nutrients. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 45-49 17218776-6 2007 We therefore assessed the effects of treatment with the RTK antagonist alone and in combination with rapamycin on mTOR targeted proteins. Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 114-118 17110594-4 2007 Hypoxia (1% O(2)) rapidly (>30 minutes) and in a concentration-dependent manner promoted rapamycin-sensitive and sustained phosphorylation of mTOR-Ser2448 followed by nuclear translocation in RAECs. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 145-149 16952420-0 2007 Effects of rapamycin on cell proliferation and phosphorylation of mTOR and p70(S6K) in HepG2 and HepG2 cells overexpressing constitutively active Akt/PKB. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 66-70 17200203-5 2007 Accordingly, the enhanced synthesis of fibrillin-1 was blocked by rapamycin, an inhibitor of mTOR. Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 93-97 16952420-3 2007 Therefore, the effects of insulin and rapamycin (an inhibitor of mTOR) on the phosphorylation of mTOR (Ser 2448) and p70(S6K) (Thr 389) as well as on cell proliferation in parental HepG2 cells and HepG2 cells overexpressing constitutively active Akt/PKB (HepG2-CA-Akt/PKB) were studied. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 97-101 17393579-5 2007 Importantly, mutations in upstream negative regulators of mTOR cause hamartomas, haemangiomas, and cancers that are sensitive to rapamycin treatment. Sirolimus 129-138 mechanistic target of rapamycin kinase Homo sapiens 58-62 17110454-6 2007 Inhibition of mTOR by rapamycin blocks clot retraction by human platelets. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 17335296-1 2007 Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor that inhibits cell cycle progression and has proven to be a potent immunosuppressive agent for use in solid organ transplant recipients. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 15-44 17210710-7 2007 Critical components in the translational machinery, such as phosphorylated mammalian target of rapamycin (mTOR) and its downstream targets, phosphorylated eukaryotic translation initiation factor and p70 S6 kinase, were up-regulated following NO treatment, and inhibition of mTOR with rapamycin attenuated NO induced increase of cyclin D1 and ODC. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 106-110 17210710-7 2007 Critical components in the translational machinery, such as phosphorylated mammalian target of rapamycin (mTOR) and its downstream targets, phosphorylated eukaryotic translation initiation factor and p70 S6 kinase, were up-regulated following NO treatment, and inhibition of mTOR with rapamycin attenuated NO induced increase of cyclin D1 and ODC. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 275-279 18034588-8 2007 Because of activation of the mammalian target of rapamycin (mTOR) pathway, the use of sirolimus (rapamycin) an mTOR inhibitor, markedly reduced cyst formation and decreased polycystic kidney size in several animal models. Sirolimus 86-95 mechanistic target of rapamycin kinase Homo sapiens 29-58 18034588-8 2007 Because of activation of the mammalian target of rapamycin (mTOR) pathway, the use of sirolimus (rapamycin) an mTOR inhibitor, markedly reduced cyst formation and decreased polycystic kidney size in several animal models. Sirolimus 86-95 mechanistic target of rapamycin kinase Homo sapiens 60-64 18034588-8 2007 Because of activation of the mammalian target of rapamycin (mTOR) pathway, the use of sirolimus (rapamycin) an mTOR inhibitor, markedly reduced cyst formation and decreased polycystic kidney size in several animal models. Sirolimus 86-95 mechanistic target of rapamycin kinase Homo sapiens 111-115 17335296-1 2007 Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor that inhibits cell cycle progression and has proven to be a potent immunosuppressive agent for use in solid organ transplant recipients. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 46-50 16962100-9 2007 Rapamycin, which inhibits mTOR leading to inactivation of p70(S6K), did not affect acetaldehyde-induced inhibition on phosphorylation of Akt and mTOR. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 26-30 17895299-2 2007 The immunosuppressive effect of sirolimus is due to inhibition of the mammalian target of rapamycin, necessary for the proliferation and clonal expansion of activated T-cells. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 70-99 16912221-3 2006 This study shows that in follicular lymphoma (FL) cells, mTOR is active because the cells displayed rapamycin-sensitive phosphorylation of p70S6 kinase and 4E-BP1. Sirolimus 100-109 mechanistic target of rapamycin kinase Homo sapiens 57-61 17259349-8 2007 Phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was found to regulate PDCD4 expression because inhibition of PI3K by LY294002 and wortmannin or of mTOR by rapamycin induced PDCD4 protein and mRNA expression. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 72-76 17142137-4 2006 Rapamycin, a uniquely specific mTOR inhibitor with clinical applications, increased fatty acid oxidation by 60% accompanied by increased activities of carnitine palmitoyltransferases I and II, the former believed to be the primary intracellular regulatory enzyme of the fatty acid oxidation pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 31-35 17167087-4 2006 When the activation of mTOR was prevented by posttraining injection of rapamycin into the amygdala, formation of the memory and the increase in p70s6 kinase phosphorylation was attenuated. Sirolimus 71-80 mechanistic target of rapamycin kinase Homo sapiens 23-27 16929481-6 2006 Inhibition of the kinase mTOR, a key player in the integration of nutrition and growth signals into protein synthesis, with rapamycin reduced serine phosphorylation of eIF3i and resulted in a loss of anchorage-independent growth. Sirolimus 124-133 mechanistic target of rapamycin kinase Homo sapiens 25-29 17050735-4 2006 In the presence of rapamycin, which induces a tight association between FKBP (FK506-binding protein) and FRAP (FKBP-rapamycin-associated protein), an FKBP-tagged Golgi enzyme can be trapped when it visits the ER by an ER-retained protein fused to FRAP. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 105-109 17050735-4 2006 In the presence of rapamycin, which induces a tight association between FKBP (FK506-binding protein) and FRAP (FKBP-rapamycin-associated protein), an FKBP-tagged Golgi enzyme can be trapped when it visits the ER by an ER-retained protein fused to FRAP. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 111-144 17050735-4 2006 In the presence of rapamycin, which induces a tight association between FKBP (FK506-binding protein) and FRAP (FKBP-rapamycin-associated protein), an FKBP-tagged Golgi enzyme can be trapped when it visits the ER by an ER-retained protein fused to FRAP. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 247-251 17142137-7 2006 Rapamycin treatment also decreased baseline phosphorylation of mTOR residues S2448 and S2481 by 30% and almost completely abolished p70 S6 kinase phosphorylation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 63-67 17142137-8 2006 These results show that rapamycin causes a metabolic shift from glucose utilization to fatty acid oxidation in model muscle cells in the presence of nutrient abundance and underline the importance of mTOR as a key regulator in glucose and lipid metabolism. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 200-204 17124526-4 2006 A new class of drugs (inhibitors of mammalian target of rapamycin) that includes sirolimus is being increasingly used in stable kidney transplant recipients. Sirolimus 81-90 mechanistic target of rapamycin kinase Homo sapiens 36-65 17175265-12 2006 Our discovery of IRI-induced up-regulation of genes associated with calcineurin and mTOR pathways are consistent with clinical observations that FK506 and Rapamycin can alter the course of DGF. Sirolimus 155-164 mechanistic target of rapamycin kinase Homo sapiens 84-88 17121904-5 2006 RESULTS: In this study, we showed that the combination of rapamycin and 17-AAG synergistically inhibited proliferation, induced apoptosis and cell cycle arrest, induced cleavage of poly(ADP-ribose) polymerase and caspase-8/caspase-9, and dysregulated signaling in the phosphatidylinositol 3-kinase/AKT/mTOR and cyclin D1/retinoblastoma pathways. Sirolimus 58-67 mechanistic target of rapamycin kinase Homo sapiens 302-306 16981910-3 2006 Rapamycin, a central immunosuppressant in islet transplantation, is an mTOR inhibitor that has been shown to inhibit cancer angiogenesis. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 71-75 17121928-8 2006 Consistent with this, the mTOR inhibitor rapamycin strongly potentiated As(2)O(3)-mediated suppression of primitive leukemic progenitors from the bone marrow of chronic myelogenous leukemia patients. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 26-30 16955484-7 2006 This phenomenon is associated with caspase-3 activation, and inhibition of mTOR by the inhibitor rapamycin enhances Abeta-induced cell death. Sirolimus 97-106 mechanistic target of rapamycin kinase Homo sapiens 75-79 16959214-5 2006 It would seem that this increase in VEGFR-3 occurred via the ERK and mTOR pathways, since their respective inhibitors U0126, LY294002 or rapamycin were responsible for a decrease of VEGFR-3. Sirolimus 137-146 mechanistic target of rapamycin kinase Homo sapiens 69-73 17041628-2 2006 Rapamycin, the naturally occurring inhibitor of mTOR, along with a number of recently developed rapamycin analogs (rapalogs) consisting of synthetically derived compounds containing minor chemical modifications to the parent structure, inhibit the growth of cell lines derived from multiple tumor types in vitro, and tumor models in vivo. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 48-52 16919239-5 2006 The activity of mammalian target of rapamycin (mTOR) is essential for phosphorylation of S6K1 and the treatment of dermal fibroblasts with rapamycin, a potent inhibitor of mTOR abolished procollagen I production. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 47-51 17047067-3 2006 The mTOR inhibitor rapamycin and its derivatives are cytotoxic to a number of cell lines. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 16952420-5 2007 Rapamycin treatment partially decreased the phosphorylation of mTOR but completely abolished the phosphorylation of p70(S6K) in the absence as well as presence of insulin in both cell lines. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 63-67 16919239-5 2006 The activity of mammalian target of rapamycin (mTOR) is essential for phosphorylation of S6K1 and the treatment of dermal fibroblasts with rapamycin, a potent inhibitor of mTOR abolished procollagen I production. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 172-176 16870609-3 2006 mTORC1 (mTOR complex 1) is rapamycin-sensitive and regulates the rate of protein synthesis in part by phosphorylating two well established effectors, S6K1 (p70 ribosomal S6 kinase 1) and 4E-BP1 (eukaryotic initiation factor 4E-binding protein 1). Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 0-4 17023663-2 2006 We found that the mTOR inhibitor, rapamycin, increased the Kv1.1 voltage-gated potassium channel protein in hippocampal neurons and promoted Kv1.1 surface expression on dendrites without altering its axonal expression. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 18-22 16874098-4 2006 In rapamycin-treated HEK293 cells, there was little accumulation of endogenous GABARAP-PL, even in the presence of lysosomal protease-inhibitors, whereas there was significant accumulation of endogenous LC3-II, together with inactivation of the mTor kinase-signaling pathway. Sirolimus 3-12 mechanistic target of rapamycin kinase Homo sapiens 245-249 16989597-4 2006 Rapamycin and its analogues CCI-779, RAD-001 and AP-23573 are known specific inhibitors of the mTOR kinase. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 95-99 17018601-4 2006 The phosphoinositide-3-kinase inhibitor, wortmannin, and the mTOR inhibitor, rapamycin, blocked E(2)-induced activation of p70 ribosomal protein S6 kinase. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 61-65 16896936-0 2006 The impact of the mTOR inhibitor sirolimus on the proliferation and function of pancreatic islets and ductal cells. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 18-22 16969122-3 2006 Inhibitors of mTOR currently under evaluation in cancer clinical trials are rapamycin (also known as sirolimus, Wyeth) and derivatives temsirolimus (CCI-779, Wyeth), everolimus, (RAD001, Novartis Pharma AG), and AP23573 (Ariad Pharmaceuticals). Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 14-18 16816403-5 2006 The stimulation of S6K1 in response to PGF2alpha treatment was abolished by the mTOR inhibitor rapamycin. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 80-84 16959613-4 2006 Furthermore, in TSC2(-/-) MEFs, the rapamycin-mediated inhibition of deregulated mTOR activity restored NF-kappaB activation and survival. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 81-85 16682955-7 2006 This may reflect both inhibition of PI-3 kinase pathways and mammalian target of rapamycin (mTOR)-dependent signaling, as the phosphorylation of Thr389 site was sensitive to treatment with the PI3-K and mTOR inhibitors, LY294002 and rapamycin, respectively. Sirolimus 81-90 mechanistic target of rapamycin kinase Homo sapiens 92-96 16682955-7 2006 This may reflect both inhibition of PI-3 kinase pathways and mammalian target of rapamycin (mTOR)-dependent signaling, as the phosphorylation of Thr389 site was sensitive to treatment with the PI3-K and mTOR inhibitors, LY294002 and rapamycin, respectively. Sirolimus 81-90 mechanistic target of rapamycin kinase Homo sapiens 203-207 16847060-5 2006 Disruption of this complex following treatment with the mTOR pharmacological inhibitor rapamycin lowered mitochondrial membrane potential, oxygen consumption, and ATP synthetic capacity. Sirolimus 87-96 mechanistic target of rapamycin kinase Homo sapiens 56-60 16959574-5 2006 Inhibition of mTOR by rapamycin blocks Wnt-induced cell growth and tumor development, suggesting a potential therapeutic value of rapamycin for cancers with activated Wnt signaling. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 16966063-1 2006 Sirolimus (SRL, rapamycin) is a potent immunosuppressive drug that binds to and inhibits mammalian Target Of Rapamycine (mTOR) kinase activity, a central controller of cell growth. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 89-119 16939811-5 2006 Rapamycin and LY294002 suppressed pS6 in 10 of 11 cases that showed increased basal levels, consistent with phosphatidylinositol 3 (PI3)-kinase/Akt/mTOR signaling being the predominant upstream signaling pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 148-152 17026798-5 2006 Rapamycin and its analogues, including temsirolimus, everolimus, and AP23573, block the mTOR signaling pathway and induce a cellular state akin to starvation, with significant antitumor activity in a variety of malignancies, including renal cell carcinoma (RCC). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 88-92 17026798-6 2006 Current data from ongoing clinical trials suggest that mTOR-targeted therapy with rapamycin derivatives is well tolerated with significant clinical activity in patients with advanced-stage RCC. Sirolimus 82-91 mechanistic target of rapamycin kinase Homo sapiens 55-59 16966063-1 2006 Sirolimus (SRL, rapamycin) is a potent immunosuppressive drug that binds to and inhibits mammalian Target Of Rapamycine (mTOR) kinase activity, a central controller of cell growth. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 121-125 16966063-1 2006 Sirolimus (SRL, rapamycin) is a potent immunosuppressive drug that binds to and inhibits mammalian Target Of Rapamycine (mTOR) kinase activity, a central controller of cell growth. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 89-119 16966063-1 2006 Sirolimus (SRL, rapamycin) is a potent immunosuppressive drug that binds to and inhibits mammalian Target Of Rapamycine (mTOR) kinase activity, a central controller of cell growth. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 121-125 16922504-7 2006 Hence, we have identified compounds that can directly mimic rapamycin or can dissociate the FRB binding from the inhibition of the catalytic activity of mTOR. Sirolimus 60-69 mechanistic target of rapamycin kinase Homo sapiens 153-157 16597595-3 2006 Surprisingly, the mTOR inhibitor rapamycin induces only apoptosis in HMC-1 cells bearing the D816V but not the V560G mutation. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 18-22 16871590-4 2006 Immunosuppressive drugs used were tacrolimus (a calcineurin inhibitor) and its synergistic partners, rapamycin (a regulator of the mammalian target of rapamycin [mTOR]) and mycophenolate mofetil (an inosine monophosphate dehydrogenase inhibitor). Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 131-160 16885382-5 2006 DHT treatment increased mTOR activity as assessed by phosphorylation of the downstream targets p70 S6 kinase and 4E-BP1, and mTOR inhibition with rapamycin blocked the DHT-stimulated increase in cyclin D proteins. Sirolimus 146-155 mechanistic target of rapamycin kinase Homo sapiens 24-28 16885382-5 2006 DHT treatment increased mTOR activity as assessed by phosphorylation of the downstream targets p70 S6 kinase and 4E-BP1, and mTOR inhibition with rapamycin blocked the DHT-stimulated increase in cyclin D proteins. Sirolimus 146-155 mechanistic target of rapamycin kinase Homo sapiens 125-129 16899564-6 2006 PRL activation of mTOR was inhibited by rapamycin (mTOR inhibitor), LY249002, and wortmannin (P13K inhibitors), but not by AG490 (Jak2 inhibitor), indicating that it was mediated by the P13K/Akt, but not Jak2, pathway. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 18-22 16807405-2 2006 On the basis of in vitro studies, the mTOR inhibitor rapamycin has been reported to lead to enhanced activation of AKT by relieving this feedback inhibition on IRS function. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 38-42 16899564-6 2006 PRL activation of mTOR was inhibited by rapamycin (mTOR inhibitor), LY249002, and wortmannin (P13K inhibitors), but not by AG490 (Jak2 inhibitor), indicating that it was mediated by the P13K/Akt, but not Jak2, pathway. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 51-55 16951268-3 2006 Because the mammalian target of the rapamycin (mTOR) pathway contributes to the activation of NF-kappaB through immunophilin/mTOR signaling, we investigated: (a) the immunohistochemical expression and state of activation and potential clinical significance of components of the mTOR signal transduction pathway in SCCT patients (morphoproteomics); and (b) the inhibitory effects of rapamycin on the growth and state of activation of mTOR in 2 HNSCC cell lines (pharmacoproteomics). Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 47-51 16769083-1 2006 Rapamycin (sirolimus) is an antibiotic that inhibits protein synthesis through mammalian target of rapamycin (mTOR) signaling and is used as an immunosuppressant in the treatment of organ rejection in transplant recipients. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 79-108 16769083-1 2006 Rapamycin (sirolimus) is an antibiotic that inhibits protein synthesis through mammalian target of rapamycin (mTOR) signaling and is used as an immunosuppressant in the treatment of organ rejection in transplant recipients. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 110-114 16769083-1 2006 Rapamycin (sirolimus) is an antibiotic that inhibits protein synthesis through mammalian target of rapamycin (mTOR) signaling and is used as an immunosuppressant in the treatment of organ rejection in transplant recipients. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 79-108 16769083-1 2006 Rapamycin (sirolimus) is an antibiotic that inhibits protein synthesis through mammalian target of rapamycin (mTOR) signaling and is used as an immunosuppressant in the treatment of organ rejection in transplant recipients. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 110-114 16818631-8 2006 We also show that inhibition of mTOR with rapamycin, as well as silencing mTOR gene product expression using mTOR-specific small interfering RNA, decreased phosphorylation of mTOR signaling proteins and induced cell cycle arrest and apoptosis in ALK+ ALCL cells. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 32-36 16855395-4 2006 Since rapamycin is a highly specific inhibitor of a protein kinase called the mammalian target of rapamycin (mTOR), many investigators have concluded that mTOR signaling is necessary for the mechanically induced growth of skeletal muscle. Sirolimus 6-15 mechanistic target of rapamycin kinase Homo sapiens 78-107 16855395-4 2006 Since rapamycin is a highly specific inhibitor of a protein kinase called the mammalian target of rapamycin (mTOR), many investigators have concluded that mTOR signaling is necessary for the mechanically induced growth of skeletal muscle. Sirolimus 6-15 mechanistic target of rapamycin kinase Homo sapiens 109-113 16855395-4 2006 Since rapamycin is a highly specific inhibitor of a protein kinase called the mammalian target of rapamycin (mTOR), many investigators have concluded that mTOR signaling is necessary for the mechanically induced growth of skeletal muscle. Sirolimus 6-15 mechanistic target of rapamycin kinase Homo sapiens 155-159 16916489-5 2006 Rapamycin (sirolimus), the prototypic mTOR inhibitor, exhibits activity in acute myeloid leukemia. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 38-42 16916489-5 2006 Rapamycin (sirolimus), the prototypic mTOR inhibitor, exhibits activity in acute myeloid leukemia. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 38-42 16877971-4 2006 METHODS: Male FVB/N mice underwent transverse aortic constriction (TAC) for 5 weeks to allow for establishment of LVH, followed by treatment with the mTOR inhibitor, Rapamune (2 mg/kg per day, gavage), for 4 weeks. Sirolimus 166-174 mechanistic target of rapamycin kinase Homo sapiens 150-154 16877971-11 2006 CONCLUSION: Despite sustained pressure overload, inhibition of mTOR by a 4-week period of Rapamune treatment attenuates chronically established LVH and cardiac fibrosis with preserved contractile function. Sirolimus 90-98 mechanistic target of rapamycin kinase Homo sapiens 63-67 16717100-7 2006 Phosphorylation of p70(S6K), a known target of mTOR, occurred rapidly following T3 treatment and was inhibited by rapamycin and wortmannin. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 47-51 16730658-8 2006 Preincubation of the oocytes for 24 h with rapamycin (50 nM) did not significantly affect Ip in the absence of mTOR but virtually abolished the increase of Ip following coexpression of mTOR. Sirolimus 43-52 mechanistic target of rapamycin kinase Homo sapiens 185-189 16951268-11 2006 Rapamycin in a dose-dependent fashion inhibited growth more in SCC-15, which correlated with a greater reduction in constitutively activated p-mTOR (Ser 2448) as shown by Western blotting. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 143-147 16951269-3 2006 The aim of this study was to evaluate the expression and activation of the Akt-mTOR-p70S6K pathway in renal cell carcinoma (RCC), seeking to strengthen the rationale for targeted therapy of RCC using rapamycin or a rapamycin analogue. Sirolimus 200-209 mechanistic target of rapamycin kinase Homo sapiens 79-83 16951269-3 2006 The aim of this study was to evaluate the expression and activation of the Akt-mTOR-p70S6K pathway in renal cell carcinoma (RCC), seeking to strengthen the rationale for targeted therapy of RCC using rapamycin or a rapamycin analogue. Sirolimus 215-224 mechanistic target of rapamycin kinase Homo sapiens 79-83 16819968-4 2006 Blockade of the mammalian targets of rapamycin (mTOR)/70 kDa ribosomal S6 kinase 1 (S6K1) pathway by the specific inhibitor rapamycin greatly enhanced M. tbc-induced IL-12/IL-23 p40 (p40) and IL-23 p19 (p19) mRNA and IL-23 protein expression. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 48-52 16819968-4 2006 Blockade of the mammalian targets of rapamycin (mTOR)/70 kDa ribosomal S6 kinase 1 (S6K1) pathway by the specific inhibitor rapamycin greatly enhanced M. tbc-induced IL-12/IL-23 p40 (p40) and IL-23 p19 (p19) mRNA and IL-23 protein expression. Sirolimus 124-133 mechanistic target of rapamycin kinase Homo sapiens 48-52 17309148-4 2006 Previous reports demonstrated that rapamycin, which inhibits mTOR activity, sensitizes certain resistant cancer cells to chemotherapeutic agents. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 61-65 16815851-4 2006 The proliferation signal inhibitors (PSIs)/mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus have shown considerable promise in reducing acute rejection in renal transplant recipients. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 43-72 16815851-4 2006 The proliferation signal inhibitors (PSIs)/mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus have shown considerable promise in reducing acute rejection in renal transplant recipients. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 74-78 16815856-2 2006 Conversion from CNI-based regimens to proliferation signal inhibitors or mammalian target of rapamycin inhibitors, such as everolimus and sirolimus, has been associated with an improvement in cardiovascular risk. Sirolimus 138-147 mechanistic target of rapamycin kinase Homo sapiens 73-102 16815857-2 2006 The proliferation signal inhibitors/mammalian target of rapamycin inhibitors everolimus and sirolimus may play an important role in achieving CNI withdrawal. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 36-65 16575396-12 2006 This high incidence of mTOR signaling pathway activation suggests that treatment with mTOR inhibitors, such as Rapamycin, may benefit patients with angiomyolipomas independent of the detection of TSC1/TSC2 loss of heterozygosity. Sirolimus 111-120 mechanistic target of rapamycin kinase Homo sapiens 23-27 16575396-12 2006 This high incidence of mTOR signaling pathway activation suggests that treatment with mTOR inhibitors, such as Rapamycin, may benefit patients with angiomyolipomas independent of the detection of TSC1/TSC2 loss of heterozygosity. Sirolimus 111-120 mechanistic target of rapamycin kinase Homo sapiens 86-90 16651733-6 2006 Wortmannin and rapamycin were demonstrated to deactivate suppression of AQP3 expression by insulin and troglitazone, suggesting that the signal transducers, phosphoinositide 3 kinase (PI3K) and the mammalian target of rapamycin (mTOR), are involved in the signal pathway for regulating transcription of AQP3. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 198-227 16651733-6 2006 Wortmannin and rapamycin were demonstrated to deactivate suppression of AQP3 expression by insulin and troglitazone, suggesting that the signal transducers, phosphoinositide 3 kinase (PI3K) and the mammalian target of rapamycin (mTOR), are involved in the signal pathway for regulating transcription of AQP3. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 229-233 16627974-7 2006 HIF-1alpha activity was found to be required in Akt-induced melanocyte transformation and tumor growth and it was suppressed greatly by mTOR inhibition with rapamycin. Sirolimus 157-166 mechanistic target of rapamycin kinase Homo sapiens 136-140 16540312-0 2006 Inhibition of the mammalian target of rapamycin (mTOR) by rapamycin increases chemosensitivity of CaSki cells to paclitaxel. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 49-53 16651424-5 2006 In addition, we found that inhibition of p53 by NIC-1 mainly occurs through mammalian target of rapamycin (mTOR) using phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) pathway as the mTOR inhibitor, rapamycin treatment abrogated NIC-1 inhibition of p53 and reversed the chemoresistance. Sirolimus 96-105 mechanistic target of rapamycin kinase Homo sapiens 107-111 16651424-5 2006 In addition, we found that inhibition of p53 by NIC-1 mainly occurs through mammalian target of rapamycin (mTOR) using phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) pathway as the mTOR inhibitor, rapamycin treatment abrogated NIC-1 inhibition of p53 and reversed the chemoresistance. Sirolimus 96-105 mechanistic target of rapamycin kinase Homo sapiens 198-202 16540312-12 2006 Pre-treatment with rapamycin inhibited activation of mTOR signalling and significantly enhanced the sensitivity of CaSki cells to paclitaxel by increasing apoptotic cell death. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 53-57 16427044-7 2006 The IFN-gamma-induced dephosphorylation of pY-STAT3, however, was inhibited when the mTOR pathway was specifically blocked by rapamycin. Sirolimus 126-135 mechanistic target of rapamycin kinase Homo sapiens 85-89 16775502-8 2006 The inhibitory effects of amino acids are reverted by the mTor inhibitor rapamycin. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 58-62 16545079-9 2006 Inhibition of mTOR by rapamycin markedly impairs insulin-activated protein synthesis. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 16466692-6 2006 Preincubation of the oocytes for 32 h with rapamycin (50 nM) decreased the creatine-induced current and abrogated its stimulation by mTOR. Sirolimus 43-52 mechanistic target of rapamycin kinase Homo sapiens 133-137 16410300-7 2006 Rapamycin, a specific inhibitor of the FRAP/mammalian target of rapamycin/p70(s6k) pathway, prevented GD-IgG-provoked IL-16 synthesis. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 44-73 16497721-2 2006 Rapamycin, a lipophilic, macrolide antibiotic, induces autophagy by inactivating the protein mammalian target of rapamycin (mTOR). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 93-122 16497721-2 2006 Rapamycin, a lipophilic, macrolide antibiotic, induces autophagy by inactivating the protein mammalian target of rapamycin (mTOR). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 124-128 16647452-1 2006 The mTOR inhibitor sirolimus improves renal transplant function compared with the nephrotoxic calcineurin inhibitors. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 16537399-9 2006 Furthermore, we showed that mTOR signaling was partially resistant to rapamycin in muscles subjected to mechanical stimulation. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 28-32 16626322-3 2006 Among these drugs are for example thalidomide,COX-2 inhibitors, PPARgamma agonists (thiazolidindiones) and mTOR antagonists (rapamycin). Sirolimus 125-134 mechanistic target of rapamycin kinase Homo sapiens 107-111 16282343-3 2006 We show that phosphorylation of mTOR, p70S6K1, and 4E-BP1 was diminished in thrombopoietin-cultured human MKs after rapamycin treatment. Sirolimus 116-125 mechanistic target of rapamycin kinase Homo sapiens 32-36 16193082-4 2005 Mechanistic studies showed that inhibition of the mTOR pathway by rapamycin alone sufficiently suppressed the phosphorylation of the downstream molecules p70S6K and 4E-BP-1, but only caused a moderate cytostatic effect. Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 50-54 16546986-3 2006 To assess the spectrum of activity in other cell types and to compare PIAs with other inhibitors of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, we compared growth inhibition by PIAs against the PI3K inhibitors LY294002 and wortmannin and the mTOR inhibitor rapamycin in the NCI60 cell line panel. Sirolimus 165-174 mechanistic target of rapamycin kinase Homo sapiens 176-180 16452206-2 2006 In model systems, tumors exhibiting mutational activation of phosphoinositide-3-kinase/Akt kinase, a common event in cancers, are hypersensitive to mTOR inhibitors, including rapamycin. Sirolimus 175-184 mechanistic target of rapamycin kinase Homo sapiens 148-152 16452206-4 2006 We now show that mTOR inhibition induces insulin receptor substrate-1 expression and abrogates feedback inhibition of the pathway, resulting in Akt activation both in cancer cell lines and in patient tumors treated with the rapamycin derivative, RAD001. Sirolimus 224-233 mechanistic target of rapamycin kinase Homo sapiens 17-21 16404421-5 2006 Importantly, mutations in upstream negative regulators of mTOR cause hamartomas, haemangiomas, and cancers that are sensitive to rapamycin treatment. Sirolimus 129-138 mechanistic target of rapamycin kinase Homo sapiens 58-62 16859513-0 2006 The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 17100699-7 2006 Sirolimus (SRL), as the first member of mTOR inhibitors, has been utilized in many clinical trials with respect to its benefit-risk assessment. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 40-44 17717968-5 2006 Sirolimus is a member of the mammalian target of rapamycin (mTOR) family. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 29-58 17717968-5 2006 Sirolimus is a member of the mammalian target of rapamycin (mTOR) family. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 60-64 16431291-3 2006 METHODS: We examined the apoptotic effects of the calcineurin inhibitor cyclosporine A and mTOR inhibitor rapamycin on the apoptotic alterations that occur in allospecifically activated human lymphocytes in a one-way mixed lymphocyte culture (MLC). Sirolimus 106-115 mechanistic target of rapamycin kinase Homo sapiens 91-95 16339025-6 2005 A rapamycin-resistant mutant of mTOR "rescued" the morphogenetic effects of PI3K in the presence of rapamycin. Sirolimus 2-11 mechanistic target of rapamycin kinase Homo sapiens 32-36 15895362-7 2005 The activity of mammalian target of rapamycin (mTOR) is essential for phosphorylation of S6K1 and the treatment malanoma cells with rapamycin, a potent inhibitor of mTOR effectively induced melanogenesis. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 47-51 15895362-7 2005 The activity of mammalian target of rapamycin (mTOR) is essential for phosphorylation of S6K1 and the treatment malanoma cells with rapamycin, a potent inhibitor of mTOR effectively induced melanogenesis. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 165-169 16489035-3 2006 We assessed both effects to understand the mechanism by which mTOR inhibitors like rapamycin sensitize multiple myeloma cells to dexamethasone-induced apoptosis. Sirolimus 83-92 mechanistic target of rapamycin kinase Homo sapiens 62-66 16434506-1 2006 Sirolimus (SRL) is a mammalian target of rapamycin inhibitor that, in contrast to cyclosporine (CsA), has been shown to inhibit rather than promote cancers in experimental models. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 21-50 16339216-10 2006 Both phenotypes are rescued after pre-treatment with the mTOR inhibitor rapamycin. Sirolimus 72-81 mechanistic target of rapamycin kinase Homo sapiens 57-61 17937632-0 2006 Sirolimus, the first mTOR inhibitor. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 21-25 16150937-6 2005 Furthermore, etoposide consistently decreased the engraftment of AML cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID) animals, and this effect was enhanced by coincubation with rapamycin, demonstrating that mTOR regulates survival of AML stem cells after etoposide treatment. Sirolimus 198-207 mechanistic target of rapamycin kinase Homo sapiens 228-232 16123394-9 2005 Apoptotic resistance of mesothelioma cells was significantly reduced by inhibiting either the PI3K/Akt pathway with LY294002 (47 +/- 6% apoptosis) or the mTOR pathway with rapamycin (50 +/- 17% apoptosis). Sirolimus 172-181 mechanistic target of rapamycin kinase Homo sapiens 154-158 16380505-10 2005 The mTOR antagonist, rapamycin, prevented foci formation of the A549/BMP-2 cells. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 4-8 16267020-6 2005 Of interest, this enhanced level of the phosphorylated active form of S6 was rapidly reduced in HNSCC cell lines and HNSCC xenograft models at clinically relevant doses of rapamycin, which specifically inhibits mTOR. Sirolimus 172-181 mechanistic target of rapamycin kinase Homo sapiens 211-215 16267020-8 2005 These findings identify the Akt-mTOR pathway as a potential therapeutic target for HNSCC, and may provide the rationale for the early clinical evaluation of rapamycin and its analogues in patients with HNSCC. Sirolimus 157-166 mechanistic target of rapamycin kinase Homo sapiens 32-36 16205124-2 2005 mTOR inhibitors (rapamycin, or analogues such as CCI-779, RAD001, AP23573), which have been shown to have a potent anti-neoplastic effect in many solid tumor models, are now being used in clinical trials. Sirolimus 17-26 mechanistic target of rapamycin kinase Homo sapiens 0-4 16109729-5 2005 Incubation of the slices with the mRNA translation inhibitor cycloheximide or the mammalian target of rapamycin (mTOR) inhibitor rapamycin blocked late-LTP in both "intact" and "isolated" slice preparations. Sirolimus 102-111 mechanistic target of rapamycin kinase Homo sapiens 113-117 15790787-7 2005 Moreover, the mTOR inhibitor rapamycin enhanced the suppressive effects of imatinib mesylate on primary leukemic granulocyte macrophage-colony-forming unit (CFU-GM) progenitors from patients with chronic myelogenous leukemia (CML). Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 14-18 16317089-3 2005 Although inhibitors of Akt are not yet clinically available, rapamycin, a mTOR-specific inhibitor, has long been used as an immunosuppressant, and several rapamycin analogues are now in clinical trials in oncology. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 74-78 16317089-5 2005 We show that dominant-negative mTOR diminishes phosphorylation of endogenous Akt and exogenous myristoylated Akt (mAkt), that prolonged exposure to rapamycin also inhibits Akt activation, and that this inhibition is dependent on new protein synthesis. Sirolimus 148-157 mechanistic target of rapamycin kinase Homo sapiens 31-35 16255777-0 2005 Synergistic inhibition of human melanoma proliferation by combination treatment with B-Raf inhibitor BAY43-9006 and mTOR inhibitor Rapamycin. Sirolimus 131-140 mechanistic target of rapamycin kinase Homo sapiens 116-120 16255777-12 2005 As expected, rapamycin inhibited the phosphorylation of mTOR substrates, p70S6K and 4EBP1, and BAY43-9006 inhibited phosphorylation of ERK, which is dependent on B-Raf activity. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 56-60 16244323-7 2005 As a specific inhibitor of mTOR, rapamycin has therapeutic potential for the treatment of TSC hamartomas. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 27-31 16227402-1 2005 Mammalian target of rapamycin (mTOR) inhibitors, such as rapamycin and CCI-779, have shown preclinical potential as therapy for multiple myeloma. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 31-35 15905878-2 2005 When promoted by rapamycin as prototype inhibitor, the mTOR deactivation-dependent cell size reduction was associated with slowed, but not suppressed, proliferation. Sirolimus 17-26 mechanistic target of rapamycin kinase Homo sapiens 55-59 16219581-2 2005 The mTOR inhibitor, rapamycin, inhibited proliferation in three mantle cell lymphoma (MCL) cell lines and reduced cyclin D3 expression while cyclin D1 levels remained unchanged. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 4-8 15927518-8 2005 The PI3K inhibitor LY294002 and the mTOR inhibitor rapamycin reversed the anabolic effect of IGF-I in dexamethasone-treated myotubes. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 36-40 16099428-1 2005 In 3T3-L1 adipocytes, insulin or anisomycin stimulated phosphorylation of IRS-1 at Ser(307) and Ser(636/639), both of which were partially reduced by the mTOR inhibitor, rapamycin, or the JNK inhibitor, SP600125, and were further inhibited by a combination of them. Sirolimus 170-179 mechanistic target of rapamycin kinase Homo sapiens 154-158 16140948-7 2005 Furthermore, rapamycin, a potent and specific mTOR inhibitor, suppressed profoundly proliferation of cells from all three types of transformed B cells. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 46-50 16096426-3 2005 Inhibition of mTOR in patients with cancer became more feasible after the development of rapamycin analogs with improved pharmacologic properties. Sirolimus 89-98 mechanistic target of rapamycin kinase Homo sapiens 14-18 15923340-6 2005 In human lung epithelial adenocarcinoma (A549) cells, LY303511, like rapamycin, inhibited mTOR-dependent phosphorylation of S6K, but not PI3K-dependent phosphorylation of Akt. Sirolimus 69-78 mechanistic target of rapamycin kinase Homo sapiens 90-94 16103051-7 2005 Treatment of human lung cancer cells with rapamycin suppressed the phosphorylation of p70S6 kinase and 4E-BP1, indicating an inhibition of mTOR signaling. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 139-143 16018822-8 2005 The effect of sirolimus on activation of mammalian target of rapamycin (mTOR) was measured by phosphorylation of the substrate p70s6k at T389, and activation of RhoA was measured by pull-down assay. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 41-70 16018822-8 2005 The effect of sirolimus on activation of mammalian target of rapamycin (mTOR) was measured by phosphorylation of the substrate p70s6k at T389, and activation of RhoA was measured by pull-down assay. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 72-76 16018822-10 2005 The stimulation of TF expression by sirolimus was associated with inhibition of basal activity of mTOR. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 98-102 16018822-14 2005 CONCLUSION: Although sirolimus stimulates TF protein expression in human SMC associated with inhibition of mTOR, it does not enhance TF activity released from the cells, suggesting a relatively safe profile of CYPHER stents. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 107-111 16342424-5 2005 Pretreatment of cells with PD-98059 and rapamycin, inhibitors of mitogen-activated protein kinase (ERK1/2) and mammalian target for rapamycin (mTOR), respectively, partially blocked Ang IV-mediated phosphorylation of 4EBP1. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 111-141 16342424-5 2005 Pretreatment of cells with PD-98059 and rapamycin, inhibitors of mitogen-activated protein kinase (ERK1/2) and mammalian target for rapamycin (mTOR), respectively, partially blocked Ang IV-mediated phosphorylation of 4EBP1. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 143-147 15958750-4 2005 This effect is blocked by rapamycin, indicating that the increase in EF1A expression is mediated by the mammalian target of rapamycin (mTOR) pathway. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 104-133 15958750-4 2005 This effect is blocked by rapamycin, indicating that the increase in EF1A expression is mediated by the mammalian target of rapamycin (mTOR) pathway. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 135-139 15937108-8 2005 Importantly, tumor cell lines derived from NF1 patients, and a genetically engineered cell system that requires Nf1-deficiency for transformation, are highly sensitive to the mTOR inhibitor rapamycin. Sirolimus 190-199 mechanistic target of rapamycin kinase Homo sapiens 175-179 15846119-8 2005 Like the mTOR inhibitor rapamycin, the patellazoles inhibit translation through the 4EBP1 and S6 kinase pathways. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 9-13 15914125-10 2005 Significantly, rapamycin completely inhibited the phosphorylation of p70(S6K), an mTOR-regulated kinase implicated in the control of proliferation, but had no effect on collagen or total protein synthesis. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 82-86 15784722-0 2005 Identification of mTOR as a novel bifunctional target in chronic myeloid leukemia: dissection of growth-inhibitory and VEGF-suppressive effects of rapamycin in leukemic cells. Sirolimus 147-156 mechanistic target of rapamycin kinase Homo sapiens 18-22 15784722-1 2005 The mammalian target of rapamycin (mTOR) has recently been described to be constitutively activated in Bcr-Abl-transformed cells and to mediate rapamycin-induced inhibition of growth in respective cell lines. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 35-39 15922966-6 2005 Maturation of leukemic cells into APCs was mediated at least partially via a PI3K/mTOR pathway, as the inhibitors LY294002, wortmannin, and rapamycin inhibited the maturation effect induced by the AdTNF.F(pK7) adenovirus. Sirolimus 140-149 mechanistic target of rapamycin kinase Homo sapiens 82-86 15845392-1 2005 We present immunohistochemical evidence that the mTOR/p70s6k pathway is activated in pancreatic tumors and show that the mTOR inhibitor and rapamycin analog CCI-779 potently suppresses the proliferation of pancreatic cancer cells. Sirolimus 140-149 mechanistic target of rapamycin kinase Homo sapiens 49-53 16139919-5 2005 In addition, TGF-beta1-induced ADAM12 up-regulation was blocked by the Frap/mTOR inhibitor rapamycin, which abrogated the phosphorylation of p70S6K. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 71-75 16139919-5 2005 In addition, TGF-beta1-induced ADAM12 up-regulation was blocked by the Frap/mTOR inhibitor rapamycin, which abrogated the phosphorylation of p70S6K. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 76-80 15955739-1 2005 mTOR kinase plays a central role in the activation of many cell types, and blocking mTOR function with rapamycin results in arrest of the cell cycle at the G1 phase. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 0-4 15955739-1 2005 mTOR kinase plays a central role in the activation of many cell types, and blocking mTOR function with rapamycin results in arrest of the cell cycle at the G1 phase. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 84-88 15899889-6 2005 Here we show that p70S6 kinase phosphorylates mTOR at Ser-2448 in vitro and that ectopic expression of rapamycin-resistant p70S6 kinase restores Ser-2448 phosphorylation in rapamycin-treated cells. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 46-50 16182816-1 2005 The concomitant use of calcineurin inhibitors (CNIs) with mTOR inhibitors, that is, either sirolimus (SRL) or everolimus (ERL), in de novo renal transplant patients is still debated. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 58-62 15850772-3 2005 Inhibition of the PI3K/Akt downstream target mTOR by rapamycin also significantly enhanced fludarabine-induced apoptosis. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 45-49 15591158-10 2005 GS activity was augmented only in leucine-treated rats and was completely inhibited by rapamycin, an inhibitor of mammalian target of rapamycin. Sirolimus 87-96 mechanistic target of rapamycin kinase Homo sapiens 114-143 15782132-1 2005 Rapamycin, a complex macrolide and potent fungicide, immunosuppressant and anticancer agent, is a highly specific inhibitor of mammalian target of rapamycin (mTOR). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 127-156 15782132-1 2005 Rapamycin, a complex macrolide and potent fungicide, immunosuppressant and anticancer agent, is a highly specific inhibitor of mammalian target of rapamycin (mTOR). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 158-162 15782132-6 2005 Transient transfection studies using kinase-dead and rapamycin-resistant forms of mTOR demonstrated that only the downregulation of Bcl-xL was caused by the mTOR inhibitory action of rapamycin, which prevented cap-dependent translation initiation, whereas Bax upregulation was induced by rapamycin through a mechanism independent of its mTOR inhibitory activity. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 82-86 15782132-6 2005 Transient transfection studies using kinase-dead and rapamycin-resistant forms of mTOR demonstrated that only the downregulation of Bcl-xL was caused by the mTOR inhibitory action of rapamycin, which prevented cap-dependent translation initiation, whereas Bax upregulation was induced by rapamycin through a mechanism independent of its mTOR inhibitory activity. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 157-161 15782132-6 2005 Transient transfection studies using kinase-dead and rapamycin-resistant forms of mTOR demonstrated that only the downregulation of Bcl-xL was caused by the mTOR inhibitory action of rapamycin, which prevented cap-dependent translation initiation, whereas Bax upregulation was induced by rapamycin through a mechanism independent of its mTOR inhibitory activity. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 157-161 15782132-6 2005 Transient transfection studies using kinase-dead and rapamycin-resistant forms of mTOR demonstrated that only the downregulation of Bcl-xL was caused by the mTOR inhibitory action of rapamycin, which prevented cap-dependent translation initiation, whereas Bax upregulation was induced by rapamycin through a mechanism independent of its mTOR inhibitory activity. Sirolimus 183-192 mechanistic target of rapamycin kinase Homo sapiens 82-86 15782132-6 2005 Transient transfection studies using kinase-dead and rapamycin-resistant forms of mTOR demonstrated that only the downregulation of Bcl-xL was caused by the mTOR inhibitory action of rapamycin, which prevented cap-dependent translation initiation, whereas Bax upregulation was induced by rapamycin through a mechanism independent of its mTOR inhibitory activity. Sirolimus 183-192 mechanistic target of rapamycin kinase Homo sapiens 157-161 15782132-6 2005 Transient transfection studies using kinase-dead and rapamycin-resistant forms of mTOR demonstrated that only the downregulation of Bcl-xL was caused by the mTOR inhibitory action of rapamycin, which prevented cap-dependent translation initiation, whereas Bax upregulation was induced by rapamycin through a mechanism independent of its mTOR inhibitory activity. Sirolimus 183-192 mechanistic target of rapamycin kinase Homo sapiens 157-161 15816883-3 2005 In rodents, donor antigen (e.g., a donor blood transfusion), or mTOR inhibition (e.g., sirolimus), enhances anti-CD154"s efficacy. Sirolimus 87-96 mechanistic target of rapamycin kinase Homo sapiens 64-68 15788477-6 2005 The highly specific mTOR inhibitor rapamycin blocked UNX-increased phosphorylation of both rpS6 and 4E-BP1. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 20-24 15550488-3 2005 In this study, we show that mTOR inhibition by rapamycin strongly inhibits the growth of the most immature acute myeloid leukemia (AML) cell lines through blockade in G0/G1 phase of the cell cycle. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 28-32 15827164-3 2005 We show that mTOR is activated by expression of LMP2A in carcinoma cells, leading to wortmannin- and rapamycin-sensitive inhibition of the negative regulator of translation, eukaryotic initiation factor 4E-binding protein 1, and increased c-Myc protein translation. Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 13-17 15833867-3 2005 However, the mechanisms underlying the cytotoxic effects of a selective mTOR inhibitor, rapamycin, on malignant glioma cells are poorly understood. Sirolimus 88-97 mechanistic target of rapamycin kinase Homo sapiens 72-76 15833867-5 2005 We showed that rapamycin induced autophagy but not apoptosis in rapamycin-sensitive malignant glioma U87-MG and T98G cells by inhibiting the function of mTOR. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 153-157 15833867-9 2005 These results indicate that rapamycin exerts its antitumor effect on malignant glioma cells by inducing autophagy and suggest that in malignant glioma cells a disruption of the PI3K/Akt signaling pathway could greatly enhance the effectiveness of mTOR inhibitors. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 247-251 15591312-1 2005 The contribution of mammalian target of rapamycin (mTOR) signaling to the resistance exercise-induced stimulation of skeletal muscle protein synthesis was assessed by administering rapamycin to Sprague-Dawley rats 2 h prior to a bout of resistance exercise. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 51-55 15591312-7 2005 The proportion of eIF2Bepsilon mRNA in polysomes was increased following exercise, an effect that was prevented by rapamycin treatment, suggesting that the increase in eIF2Bepsilon protein expression was mediated by an mTOR-dependent increase in translation of the mRNA encoding the protein. Sirolimus 115-124 mechanistic target of rapamycin kinase Homo sapiens 219-223 15788644-12 2005 Rapamycin, an mTOR inhibitor, had a growth-inhibitory effect in C4-2 cells, but not in LNCaP cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 15576463-4 2005 Inhibition of mTOR/S6K1 by rapamycin increased insulin-stimulated glucose transport by as much as 45% in 3T3-L1 adipocytes. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 14-18 15578690-7 2005 We found that treatment with either an mTOR kinase inhibitor (CCI-779, a rapamycin analog) or with IFN-gamma reduced the severity of TSC-related disease without significant toxicity. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 39-43 15833062-3 2005 Currently, the mTOR inhibitor rapamycin (sirolimus, Wyeth) and its derivatives temsirolimus (CCI-779, Wyeth), everolimus (RAD-001, Novartis Pharma AG) and AP-23573 (Ariad Pharmaceuticals) are being evaluated in cancer clinical trials. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 15-19 15833062-3 2005 Currently, the mTOR inhibitor rapamycin (sirolimus, Wyeth) and its derivatives temsirolimus (CCI-779, Wyeth), everolimus (RAD-001, Novartis Pharma AG) and AP-23573 (Ariad Pharmaceuticals) are being evaluated in cancer clinical trials. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 15-19 15714459-4 2005 The mTOR inhibitor, rapamycin, inhibited phosphorylation of these proteins. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 4-8 15514971-3 2005 SB 203580 and rapamycin reversed the RNA stabilization effect of IL-1beta in a dose-dependent manner, suggesting involvement of the p38/MAP kinase and mTOR pathways. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 151-155 15723049-3 2005 Deletion of S6K1 does not affect myoblast cell proliferation but reduces myoblast size to the same extent as that observed with mTOR inhibition by rapamycin. Sirolimus 147-156 mechanistic target of rapamycin kinase Homo sapiens 128-132 15537654-6 2005 In adenoviral-infected beta-cells expressing mTORDelta, the decrease in IRS-2 protein levels was also prevented by rapamycin or lactacystin, further indicating a proteasomal mediated degradation of IRS-2 mediated via mTOR-induced Ser/Thr phosphorylation of IRS-2. Sirolimus 115-124 mechanistic target of rapamycin kinase Homo sapiens 45-49 15501927-8 2005 The activation of p70S6K/S6 pathway was sensitive to inhibition by rapamycin and LY294002, indicating that mTOR and PI3K/Akt are upstream signaling regulators. Sirolimus 67-76 mechanistic target of rapamycin kinase Homo sapiens 107-111 15501954-8 2004 In vitro, we further confirmed the causal relationship between ErbB2 overexpression and mTOR activation, which was associated with enhanced invasive ability and sensitivity to a mTOR inhibitor, rapamycin. Sirolimus 194-203 mechanistic target of rapamycin kinase Homo sapiens 88-92 15522880-5 2005 IL-12-induced phosphorylation of Stat3 on Ser-727 was affected by rapamycin, which may be due to the effect of rapamycin on the IL-12-induced interaction between mammalian target of rapamycin (mTOR) and Stat3. Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 162-191 15522880-5 2005 IL-12-induced phosphorylation of Stat3 on Ser-727 was affected by rapamycin, which may be due to the effect of rapamycin on the IL-12-induced interaction between mammalian target of rapamycin (mTOR) and Stat3. Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 193-197 15657358-5 2005 RAD001 (everolimus) is an orally available mTOR inhibitor structurally related to rapamycin. Sirolimus 82-91 mechanistic target of rapamycin kinase Homo sapiens 43-47 15319277-0 2004 Combination of the mTOR inhibitor rapamycin and CC-5013 has synergistic activity in multiple myeloma. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 19-23 15489897-4 2004 Treatment of cells with the PI-3 kinase inhibitor LY294002 (10 muM) or the mTOR inhibitor rapamycin (10 nM) also reduced PMA-induced proliferation and cell-cycle progression. Sirolimus 90-99 mechanistic target of rapamycin kinase Homo sapiens 75-79 15578919-5 2004 Hyperactivation of mTOR signaling has been implicated in tumorigenesis, and promising pre-clinical studies in several tumor types suggest that the anti-proliferative and anti-angiogenic properties of rapamycin may be useful in cancer therapy. Sirolimus 200-209 mechanistic target of rapamycin kinase Homo sapiens 19-23 15501691-5 2004 Rapamycin is a potent immunosuppressant and investigational anticancer drug, which inhibits mTOR, blocking protein synthesis and arresting the cell cycle in G1 phase. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 92-96 15492868-4 2004 The combination of the anti-metabolite gemcitabine and the mTOR blocker, rapamycin, has achieved an impressive response in a patient with metastatic leiomyosarcoma. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 59-63 15691225-1 2005 Sirolimus (rapamycin) is a macrocyclic lactone isolated from a strain of Streptomyces hygroscopicus that inhibits the mammalian target of rapamycin (mTOR)-mediated signal-transduction pathways, resulting in the arrest of cell cycle of various cell types, including T- and B-lymphocytes. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 118-147 15691225-1 2005 Sirolimus (rapamycin) is a macrocyclic lactone isolated from a strain of Streptomyces hygroscopicus that inhibits the mammalian target of rapamycin (mTOR)-mediated signal-transduction pathways, resulting in the arrest of cell cycle of various cell types, including T- and B-lymphocytes. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 149-153 15691225-1 2005 Sirolimus (rapamycin) is a macrocyclic lactone isolated from a strain of Streptomyces hygroscopicus that inhibits the mammalian target of rapamycin (mTOR)-mediated signal-transduction pathways, resulting in the arrest of cell cycle of various cell types, including T- and B-lymphocytes. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 118-147 15691225-1 2005 Sirolimus (rapamycin) is a macrocyclic lactone isolated from a strain of Streptomyces hygroscopicus that inhibits the mammalian target of rapamycin (mTOR)-mediated signal-transduction pathways, resulting in the arrest of cell cycle of various cell types, including T- and B-lymphocytes. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 149-153 16372478-9 2005 Wortmannin and rapamycin, an inhibitor of mTOR, suppressed Ang1-induced p70 S6 kinase phosphorylation and partially inhibited the Ang1-induced anti-apoptotic effect. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 42-46 15623621-2 2004 The role of mTOR and S6K in hepatocellular carcinoma has not been investigated, but this pathway is of particular interest because an effective inhibitor, rapamycin, is available. Sirolimus 155-164 mechanistic target of rapamycin kinase Homo sapiens 12-16 15589136-1 2004 Recent studies show that hyperactivated mTOR, the "target of rapamycin" that senses nutrient availability in eukaryotic cells, inhibits signaling by insulin receptor substrates. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 40-44 15593048-2 2004 Sirolimus and everolimus may interfere with mTOR activity after their binding with FK binding protein. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 44-48 15501954-8 2004 In vitro, we further confirmed the causal relationship between ErbB2 overexpression and mTOR activation, which was associated with enhanced invasive ability and sensitivity to a mTOR inhibitor, rapamycin. Sirolimus 194-203 mechanistic target of rapamycin kinase Homo sapiens 178-182 15456827-8 2004 In contrast, rapamycin, an inhibitor of mTOR (mammalian target of rapamycin), altered effects of elevated Akt-1 selectively: it eliminated the increase in stem cells and reduced the proliferative response, but had no effect on survival. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 40-44 15367412-6 2004 The PTEN-negative cell line displayed greater sensitivity to the growth inhibitory effects of the PI3K inhibitor, LY294002 and rapamycin, an inhibitor of the PI3K/Akt downstream mediator mTOR, compared with the PTEN-positive cell lines. Sirolimus 127-136 mechanistic target of rapamycin kinase Homo sapiens 187-191 15367412-9 2004 These findings indicate that inhibitors of mTOR, some of which are already in clinical development (CCI-779, an ester of rapamycin), have the potential to be effective in the treatment of breast cancer patients with PTEN-negative tumors and should be evaluated in this setting. Sirolimus 121-130 mechanistic target of rapamycin kinase Homo sapiens 43-47 15452223-2 2004 However, translation is inhibited by cellular stress responses or rapamycin treatment, which inhibit mTOR kinase activity. Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 101-105 15452223-3 2004 We show that during human cytomegalovirus (HCMV) infection, viral protein synthesis and virus production proceed relatively normally when mTOR kinase activity is inhibited due to hypoxic stress or rapamycin treatment. Sirolimus 197-206 mechanistic target of rapamycin kinase Homo sapiens 138-142 15456827-8 2004 In contrast, rapamycin, an inhibitor of mTOR (mammalian target of rapamycin), altered effects of elevated Akt-1 selectively: it eliminated the increase in stem cells and reduced the proliferative response, but had no effect on survival. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 46-75 15322222-9 2004 RA-IgG-provoked IL-16 expression is inhibited by rapamycin, a specific macrolide inhibitor of the Akt/FRAP/mammalian target of rapamycin/p70(s6k) pathway, and by dexamethasone. Sirolimus 49-58 mechanistic target of rapamycin kinase Homo sapiens 102-106 15322222-9 2004 RA-IgG-provoked IL-16 expression is inhibited by rapamycin, a specific macrolide inhibitor of the Akt/FRAP/mammalian target of rapamycin/p70(s6k) pathway, and by dexamethasone. Sirolimus 49-58 mechanistic target of rapamycin kinase Homo sapiens 107-136 15235105-8 2004 In addition, there was a concentration-dependent inhibition of cell migration and p70S6K phosphorylation (Thr(389) and Thr(421)/Ser(424)) in the presence of Rapamycin, a specific inhibitor of the mammalian target of rapamycin (mTOR, a downstream of AKT). Sirolimus 157-166 mechanistic target of rapamycin kinase Homo sapiens 196-225 15235105-8 2004 In addition, there was a concentration-dependent inhibition of cell migration and p70S6K phosphorylation (Thr(389) and Thr(421)/Ser(424)) in the presence of Rapamycin, a specific inhibitor of the mammalian target of rapamycin (mTOR, a downstream of AKT). Sirolimus 157-166 mechanistic target of rapamycin kinase Homo sapiens 227-231 15279778-1 2004 The mammalian target of rapamycin (mTOR) is a large multidomain protein whose function is inhibited by the immunosuppressant drug rapamycin. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 35-39 15208659-7 2004 Rapamycin, a specific inhibitor of FRAP/mTOR (the upstream kinase of p70S6K), also blocked p70S6K activation, indicating the involvement of FRAP/mTOR activation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 35-39 15208659-7 2004 Rapamycin, a specific inhibitor of FRAP/mTOR (the upstream kinase of p70S6K), also blocked p70S6K activation, indicating the involvement of FRAP/mTOR activation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 40-44 15208659-7 2004 Rapamycin, a specific inhibitor of FRAP/mTOR (the upstream kinase of p70S6K), also blocked p70S6K activation, indicating the involvement of FRAP/mTOR activation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 140-144 15208659-7 2004 Rapamycin, a specific inhibitor of FRAP/mTOR (the upstream kinase of p70S6K), also blocked p70S6K activation, indicating the involvement of FRAP/mTOR activation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 145-149 15028555-11 2004 The mTOR inhibitor rapamycin had similar inhibitory effects on G(1) cell cycle progression and on the expression of cyclin D1, CDK4, CDC25A, and retinoblastoma phosphorylation. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 15218033-1 2004 Under serum-free conditions, rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), induces a cellular stress response characterized by rapid and sustained activation of the apoptosis signal-regulating kinase 1 (ASK1) signaling pathway and selective apoptosis of cells lacking functional p53. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 56-85 15218033-1 2004 Under serum-free conditions, rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), induces a cellular stress response characterized by rapid and sustained activation of the apoptosis signal-regulating kinase 1 (ASK1) signaling pathway and selective apoptosis of cells lacking functional p53. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 87-91 15190216-3 2004 Interestingly, lymphomas expressing Akt, but not those expressing Bcl-2 are sensitized to chemotherapy-induced apoptosis by the mTOR inhibitor rapamycin, an effect that is countered by eIF4E. Sirolimus 143-152 mechanistic target of rapamycin kinase Homo sapiens 128-132 15254091-9 2004 Finally, we observed that both PI3K inhibitors and rapamycin, an mTOR inhibitor, prevented mGluR-LTD induced by DHPG. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 65-69 15487700-5 2004 Combinatorial therapy with pamidronate and Gleevec, an inhibitor of several tyrosine kinases; Velcade, a proteasome inhibitor; or rapamycin, an inhibitor of the mammalian target of rapamycin (m-TOR) all showed additive effects in causing proliferative inhibition in MDA-175 cells. Sirolimus 130-139 mechanistic target of rapamycin kinase Homo sapiens 161-190 15066126-6 2004 Rapamycin diminished the recovery of endogenous raptor with endogenous or recombinant mTOR in vivo; this inhibition required the ability of mTOR to bind the FKBP12/rapamycin complex, but was independent of mTOR kinase activity. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 86-90 15347472-1 2004 OBJECTIVE: To investigate the inhibitory effect of the mammalian target of rapamycin (mTOR) inhibitor, sirolimus on expression of hypoxia-inducible factor (HIF)1alpha protein and growth of ovarian carcinoma in an athymic mouse xenogeneic transplant model of ovarian cancer. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 86-90 15064712-7 2004 Inhibition of the VEGF receptor and PKB/Akt-downstream PIK-related mTOR-kinase by rapamycin also neutralized the VEGF-protective effect in an PKB/Akt gene expression-independent way but results in proteolysis-dependent reduction of PKB/Akt protein stability. Sirolimus 82-91 mechanistic target of rapamycin kinase Homo sapiens 67-71 15146184-5 2004 This protects against polyglutamine toxicity, as the specific mTOR inhibitor rapamycin attenuates huntingtin accumulation and cell death in cell models of Huntington disease, and inhibition of autophagy has the converse effects. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 62-66 15150095-2 2004 We demonstrate a dramatic decrease of IFN-gamma expression in tumors and mouse embryo fibroblast cell lines that lack either Tsc1 or Tsc2, which is reversed by rapamycin (mammalian target of rapamycin inhibitor) therapy. Sirolimus 160-169 mechanistic target of rapamycin kinase Homo sapiens 171-200 14982927-6 2004 FSH-stimulated HIF-1 activity is inhibited by the PI 3-kinase inhibitor LY294002, the Rheb inhibitor FTI-277 (farnesyltransferase inhibitor-277), and the mTOR inhibitor rapamycin. Sirolimus 169-178 mechanistic target of rapamycin kinase Homo sapiens 154-158 15070696-2 2004 The use of the macrolide rapamycin, selectively inhibiting the phosphoprotein mammalian target of rapamycin (mTOR) downstream of, for example, insulin-like growth factor-I receptor (IGF-IR), possibly represents such a molecular mode of therapy. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 78-107 15070696-2 2004 The use of the macrolide rapamycin, selectively inhibiting the phosphoprotein mammalian target of rapamycin (mTOR) downstream of, for example, insulin-like growth factor-I receptor (IGF-IR), possibly represents such a molecular mode of therapy. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 109-113 15048882-4 2004 Pretreatment of the cells with wortmannin, a specific inhibitor of PI3K, or rapamycin, a specific inhibitor of mTOR kinase, prevented H2O2-increased mitosis. Sirolimus 76-85 mechanistic target of rapamycin kinase Homo sapiens 111-115 15067056-8 2004 When we examined the phosphorylation of 4EBP-1, a downstream substrate of the mammalian target of rapamycin, we found that rapamycin, but not SFA, inhibited the mammalian target of rapamycin activity. Sirolimus 98-107 mechanistic target of rapamycin kinase Homo sapiens 161-190 14726531-14 2004 Interestingly, rapamycin treatment suggests a novel connection between the mTOR pathway and eukaryotic initiation factor-2alpha phosphorylation in mammalian cells, which may not, however, be involved in TOP mRNA translational regulation. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 75-79 15056668-4 2004 Inhibition of mTOR by rapamycin or by overexpression of a kinase dead mutant of mTOR, efficiently blocked IFNalpha-induced apoptosis. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 15056668-5 2004 A PI3K and mTOR-dependent phosphorylation of p70S6 kinase and 4E-BP1 repressor was induced by IFNalpha treatment of cells and was strongly inhibited by Ly294002 or rapamycin. Sirolimus 164-173 mechanistic target of rapamycin kinase Homo sapiens 11-15 15071500-3 2004 Ser422 phosphorylation appears to be regulated by the S6Ks: (a) Ser422 phosphorylation is sensitive to pharmacological inhibitors of phosphoinositide-3 kinase and the mammalian target of rapamycin; (b) S6K1/S6K2 specifically phosphorylate Ser422 in vitro; and (c) rapamycin-resistant S6Ks confer rapamycin resistance upon Ser422 phosphorylation in vivo. Sirolimus 264-273 mechanistic target of rapamycin kinase Homo sapiens 167-196 15020250-3 2004 We further investigated the role of mTOR in regulating serine 307 phosphorylation, demonstrating that serine 307 phosphorylation in response to insulin, anisomycin, or tumor necrosis factor was quantitatively and temporally associated with activation of mTOR and could be inhibited by rapamycin. Sirolimus 285-294 mechanistic target of rapamycin kinase Homo sapiens 254-258 15066126-6 2004 Rapamycin diminished the recovery of endogenous raptor with endogenous or recombinant mTOR in vivo; this inhibition required the ability of mTOR to bind the FKBP12/rapamycin complex, but was independent of mTOR kinase activity. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 140-144 15066126-6 2004 Rapamycin diminished the recovery of endogenous raptor with endogenous or recombinant mTOR in vivo; this inhibition required the ability of mTOR to bind the FKBP12/rapamycin complex, but was independent of mTOR kinase activity. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 140-144 15016873-7 2004 Significantly, rapamycin, an inhibitor commonly used to investigate the mTOR/p70S6K pathway, reduced the in vivo phosphorylation of specific NS5A phosphopeptides, strongly suggesting that p70S6 kinase and potentially related members of this group phosphorylate NS5A inside the cell. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 72-76 15010827-4 2004 Recent studies have demonstrated that mTOR inhibition by rapamycin or its analogues have remarkable activity against a wide range of human cancers in vitro and in human tumor xenograft models. Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 38-42 15050414-12 2004 Our results also indicated that the mTOR/FRAP inhibitor, rapamycin, inhibited 4-OHE2-induced HIF-1alpha and VEGF-A expression. Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 36-40 15050414-12 2004 Our results also indicated that the mTOR/FRAP inhibitor, rapamycin, inhibited 4-OHE2-induced HIF-1alpha and VEGF-A expression. Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 41-45 15163844-9 2004 In the absence of a clear target, common downstream signal transduction proteins that are known to intersect with the ER pathway can be inhibited to address resistance, including G proteins with farnesyltransferase inhibitors and molecular target of rapamycin (mTOR) with rapamycin analogues. Sirolimus 250-259 mechanistic target of rapamycin kinase Homo sapiens 261-265 14592809-7 2004 Notably, we detected a striking rapamycin induction of calponin and SM-MHC mRNA, suggesting a role for mTOR in transcriptional control of VSMC gene expression. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 103-107 15004009-3 2004 Inhibition of mTOR signaling by rapamycin inactivates TIF-IA and impairs transcription-initiation complex formation. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 14-18 14576155-1 2004 Prior work demonstrates that AKT activity regulates sensitivity of cells to G(1) arrest induced by mammalian target of rapamycin (mTOR) inhibitors such as rapamycin and CCI-779. Sirolimus 119-128 mechanistic target of rapamycin kinase Homo sapiens 130-134 15318929-5 2004 Rapamycin is a specific mTOR antagonist that targets this pathway and blocks the downstream signaling elements, resulting in cell cycle arrest in the G1 phase. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 24-28 15565817-14 2004 Rapamycin, a specific mTOR inhibitor, has potent antitumoral activities in preclinical models of TSC and is currently undergoing phase I/II clinical studies. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 22-26 15020250-2 2004 Rapamycin, an inhibitor of the kinase mTOR, can prevent serine 307 phosphorylation and the development of insulin resistance. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 38-42 14871980-11 2004 Rapamycin inhibited the phosphorylation of S6K1, ribosomal S6 protein, and 4E-BP1 in rapamycin-resistant as well as -sensitive cells, indicating that its ability to inhibit the mTOR pathway is not sufficient to confer sensitivity to rapamycin. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 177-181 14871980-11 2004 Rapamycin inhibited the phosphorylation of S6K1, ribosomal S6 protein, and 4E-BP1 in rapamycin-resistant as well as -sensitive cells, indicating that its ability to inhibit the mTOR pathway is not sufficient to confer sensitivity to rapamycin. Sirolimus 85-94 mechanistic target of rapamycin kinase Homo sapiens 177-181 14871980-11 2004 Rapamycin inhibited the phosphorylation of S6K1, ribosomal S6 protein, and 4E-BP1 in rapamycin-resistant as well as -sensitive cells, indicating that its ability to inhibit the mTOR pathway is not sufficient to confer sensitivity to rapamycin. Sirolimus 233-242 mechanistic target of rapamycin kinase Homo sapiens 177-181 14718170-4 2004 Since treatment with rapamycin induces a tight association between FKBP and FRAP, one would expect rapamycin to trap the FKBP-fused Golgi protein in the ER if it ever visits the ER during mitosis. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 76-80 14766378-12 2004 Rapamycin also inhibits IL-2 expression, though by interaction with the mammalian Target of Rapamycin (mTOR) protein. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 72-101 14766378-12 2004 Rapamycin also inhibits IL-2 expression, though by interaction with the mammalian Target of Rapamycin (mTOR) protein. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 103-107 14681687-6 2003 We demonstrate that rapamycin, an mTOR inhibitor, efficiently blocked the proliferation of all cell lines by promoting cell cycle arrest at the G1 phase. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 34-38 14679009-10 2003 These results indicate that rapamycin exerts variable inhibitory actions on mTOR signaling functions and suggest that direct inhibitors of the mTOR kinase domain will display substantially broader anticancer activities than rapamycin. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 76-80 14679009-10 2003 These results indicate that rapamycin exerts variable inhibitory actions on mTOR signaling functions and suggest that direct inhibitors of the mTOR kinase domain will display substantially broader anticancer activities than rapamycin. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 143-147 14623952-2 2003 The mTOR inhibitor rapamycin can prevent forms of protein synthesis-dependent synaptic plasticity such as long-term facilitation in Aplysia and late-phase long-term potentiation (L-LTP) in the hippocampal CA1 region of rodents. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 12916871-0 2003 Mutant type glutathione S-transferase theta 1 gene homologue to mTOR in myelodysplastic syndrome: possible clinical application of rapamycin. Sirolimus 131-140 mechanistic target of rapamycin kinase Homo sapiens 64-68 14555183-6 2003 With regard to the involvement of mammalian target of rapamycin (mTOR) and p70 S6 kinase, angiotensin II-induced phosphorylation was abolished by pretreatment with rapamycin, but not by tosylphenylalanine chloromethyl ketone or tosyllysine chloromethyl ketone. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 65-69 12807916-9 2003 Thus, LPS and IFN-gamma activate the PI3K and mTOR pathways, which converge to regulate STAT1-dependent transcription of pro-apoptotic and pro-inflammatory genes in a rapamycin-insensitive manner. Sirolimus 167-176 mechanistic target of rapamycin kinase Homo sapiens 46-50 12914928-4 2003 However, we recently found that the regulation of the IGFBP1 but not the PEPCK or G6Pase genes by insulin was sensitive to rapamycin, an inhibitor of mTOR. Sirolimus 123-132 mechanistic target of rapamycin kinase Homo sapiens 150-154 12906785-6 2003 This dissociation is completely sensitive to rapamycin (an mTOR inhibitor) but not wortmannin (a phosphoinositide 3-kinase [PI3K] inhibitor). Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 59-63 12906785-7 2003 Rheb also activates S6K1 during amino acid insufficiency via a rapamycin-sensitive mechanism, suggesting that Rheb participates in nutrient signaling through mTOR. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 158-162 12939469-1 2003 Rapamycin exerts its biological activity by inhibiting the kinase mammalian target of rapamycin (mTOR), which regulates important cellular processes such as control of cell cycle and cell size, translation initiation, and transcription. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 66-95 12939469-1 2003 Rapamycin exerts its biological activity by inhibiting the kinase mammalian target of rapamycin (mTOR), which regulates important cellular processes such as control of cell cycle and cell size, translation initiation, and transcription. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 97-101 12939469-3 2003 Some investigators have hypothesized that loss of the PTEN tumor suppressor may sensitize tumor cells to the antiproliferative activity of rapamycin because PTEN loss leads to activation of the mTOR pathway. Sirolimus 139-148 mechanistic target of rapamycin kinase Homo sapiens 194-198 12939469-9 2003 We demonstrate that rapamycin inhibits phosphorylation of downstream targets of mTOR such as p70(S6K) kinase and 4E-BP1 translation repressor. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 80-84 12740386-4 2003 The immunosuppressant FK506 failed to inhibit p70S6K activation, but was able to rescue the rapamycin-induced downshift, pointing to a role for the mammalian target of rapamycin (mTOR) kinase. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 148-177 12740386-4 2003 The immunosuppressant FK506 failed to inhibit p70S6K activation, but was able to rescue the rapamycin-induced downshift, pointing to a role for the mammalian target of rapamycin (mTOR) kinase. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 179-183 12713446-7 2003 This activity was resistant to the effects of rapamycin or wortmannin, indicating that mammalian target of rapamycin (mTOR) and phosphoinositide 3-kinase (PI3K) regulate S6K2 activity via Thr-388. Sirolimus 46-55 mechanistic target of rapamycin kinase Homo sapiens 87-116 12713446-7 2003 This activity was resistant to the effects of rapamycin or wortmannin, indicating that mammalian target of rapamycin (mTOR) and phosphoinositide 3-kinase (PI3K) regulate S6K2 activity via Thr-388. Sirolimus 46-55 mechanistic target of rapamycin kinase Homo sapiens 118-122 12876075-3 2003 Rapamycin, a specific inhibitor of mTOR function, was found to inhibit the Akt-induced increase in cell size by 70%, presumably via inhibition of the Akt-induced increase in protein synthesis. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 35-39 14559232-8 2003 The mTOR inhibitor rapamycin has similar inhibitory effects on G(1) cell cycle progression and expression of cyclin D1, CDK4, and Rb phosphorylation. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 14500340-5 2003 Rapamycin, a mTOR inhibitor, reduced the production of VEGF by Tsc1- and Tsc2-null fibroblasts to normal levels. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 13-17 12949840-5 2003 Treatment with rapamycin inhibited EGF-induced phosphorylation and activation of ribosomal p70 S6 protein kinase (p70 S6K), an mTOR downstream target, but had no effect on phosphorylation and activation of Akt. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 127-131 12875979-14 2003 Pretreatment of cells with rapamycin (an inhibitor of FRAP/mTOR which is the immediate upstream kinase of the p70 S6 kinase) attenuated the effects induced by zinc. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 54-58 12875979-14 2003 Pretreatment of cells with rapamycin (an inhibitor of FRAP/mTOR which is the immediate upstream kinase of the p70 S6 kinase) attenuated the effects induced by zinc. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 59-63 12957289-6 2003 Rapamycin normalizes HIF levels in TSC2(-/-) cells, indicating that TSC2 regulates HIF by inhibiting mTOR. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 101-105 12912932-5 2003 Exposure of Raji lymphoblastoid cells to increasing concentrations of rapamycin resulted in a linear concentration-dependent inhibition of p70(s6) kinase activity, suggesting that p70(s6) kinase activity could be an appropriate marker for mTOR-interacting agents. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 239-243 12916871-8 2003 These results suggest that rapamycin could be included in the therapeutic modality for the patients with MDS who have the mTOR sequences in GSTT-1 gene. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 122-126 12813467-2 2003 Rapamycin is a highly specific inhibitor of mTOR in clinical trials for the treatment of breast and other cancers. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 44-48 12813467-10 2003 These data implicate mTOR as a critical target for survival signals generated by PLD and suggest that PLD levels in breast cancer could be a valuable indicator of the likely efficacy of rapamycin treatment. Sirolimus 186-195 mechanistic target of rapamycin kinase Homo sapiens 21-25 12820963-1 2003 Under serum-free conditions, rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), induces apoptosis of cells lacking functional p53. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 56-85 12800089-4 2003 Pretreatment of L6 cells with sodium orthovanadate (Na(3)VO(4)) plus the mTOR inhibitor rapamycin caused a 5-fold increase in insulin-responsive glucose uptake at 2 hours when compared to insulin alone. Sirolimus 88-97 mechanistic target of rapamycin kinase Homo sapiens 73-77 12800089-7 2003 When L6 cells were pretreated with Na(3)VO(4) plus the proteasome inhibitor MG-132 or the mTOR inhibitor rapamycin prior to insulin addition, IRS-1 mass loss as well as IRS-1/PI-3 kinase complex decay was blocked at 2 hours and PI 3-kinase activity was increased 2.5-fold and 4-fold, respectively, over insulin alone. Sirolimus 105-114 mechanistic target of rapamycin kinase Homo sapiens 90-94 12820963-1 2003 Under serum-free conditions, rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), induces apoptosis of cells lacking functional p53. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 87-91 12604610-5 2003 Raptor appears to serve as an mTOR scaffold protein, the binding of which to the TOS motif of mTOR substrates is necessary for effective mTOR-catalyzed phosphorylation in vivo and perhaps for conferring their sensitivity to rapamycin and amino acid sufficiency. Sirolimus 224-233 mechanistic target of rapamycin kinase Homo sapiens 30-34 12604610-5 2003 Raptor appears to serve as an mTOR scaffold protein, the binding of which to the TOS motif of mTOR substrates is necessary for effective mTOR-catalyzed phosphorylation in vivo and perhaps for conferring their sensitivity to rapamycin and amino acid sufficiency. Sirolimus 224-233 mechanistic target of rapamycin kinase Homo sapiens 94-98 12604610-5 2003 Raptor appears to serve as an mTOR scaffold protein, the binding of which to the TOS motif of mTOR substrates is necessary for effective mTOR-catalyzed phosphorylation in vivo and perhaps for conferring their sensitivity to rapamycin and amino acid sufficiency. Sirolimus 224-233 mechanistic target of rapamycin kinase Homo sapiens 94-98 12134068-9 2002 The mTOR inhibitor rapamycin diminished Akt-mediated increases in cell size, mitochondrial membrane potential, and cell survival. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 12742477-1 2003 Sirolimus is the first of a group of mammalian target of rapamycin inhibitors to be introduced for clinical use in the United States. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 37-66 12742500-4 2003 Sirolimus targets a unique serine-threonine kinase, mammalian target of rapamycin (mTor), which plays a key role in mitogenic and nutritional cells signals. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 52-81 12742500-4 2003 Sirolimus targets a unique serine-threonine kinase, mammalian target of rapamycin (mTor), which plays a key role in mitogenic and nutritional cells signals. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 83-87 12647306-8 2003 Treatment of cells with rapamycin, an inhibitor of the mammalian target of mTOR, resulted in a 47% and a 53% decrease in the AP activity induced by OP-1 alone and by OP-1 plus IGF-I, respectively. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 75-79 12681504-5 2003 Amino acid-induced S6K1 activation was inhibited by LY294002 (PI3-kinase inhibitor) and rapamycin (inhibitor of the mammalian target of rapamycin, mTOR), suggesting the involvement of an avian homolog of mTOR. Sirolimus 88-97 mechanistic target of rapamycin kinase Homo sapiens 116-145 12681504-5 2003 Amino acid-induced S6K1 activation was inhibited by LY294002 (PI3-kinase inhibitor) and rapamycin (inhibitor of the mammalian target of rapamycin, mTOR), suggesting the involvement of an avian homolog of mTOR. Sirolimus 88-97 mechanistic target of rapamycin kinase Homo sapiens 147-151 12569580-7 2003 Progression of the cell cycle from G1 to S phase was inhibited up to 90% by wortmannin or rapamycin, an inhibitor of mTOR, which acts downstream of PI3K. Sirolimus 90-99 mechanistic target of rapamycin kinase Homo sapiens 117-121 12504590-5 2002 Tsc2 null NEP cells express high levels of phosphorylated S6kinase, S6, Stat3, and 4E-BP-1, which is reversed by treatment with rapamycin, an inhibitor of mTOR. Sirolimus 128-137 mechanistic target of rapamycin kinase Homo sapiens 155-159 12393646-7 2002 BCR/ABL-induced VEGF gene expression was counteracted by the phosphoinositide 3-kinase (PI3-kinase) inhibitor LY294002 and rapamycin, an antagonist of mammalian target of rapamycin (mTOR), but not by inhibition of the mitogen-activated protein kinase pathway. Sirolimus 123-132 mechanistic target of rapamycin kinase Homo sapiens 151-180 12393646-7 2002 BCR/ABL-induced VEGF gene expression was counteracted by the phosphoinositide 3-kinase (PI3-kinase) inhibitor LY294002 and rapamycin, an antagonist of mammalian target of rapamycin (mTOR), but not by inhibition of the mitogen-activated protein kinase pathway. Sirolimus 123-132 mechanistic target of rapamycin kinase Homo sapiens 182-186 12414639-3 2002 This study aimed to determine the effects of PTEN status and treatment with rapamycin, an inhibitor of mTOR, in the response of prostate cancer cell lines to doxorubicin. Sirolimus 76-85 mechanistic target of rapamycin kinase Homo sapiens 103-107 12193593-6 2002 LY294002 and rapamycin, potent inhibitors of PI3-kinase and mTOR, respectively, also blocked the DNA synthesis induced by 5(S)-HETE. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 60-64 12393186-3 2002 Rapamycin, which binds to FRAP/mTOR and completely suppressed the activation of p70S6 kinase by insulin, almost completely blocked the induction of the hexokinase II gene, and caused an approximately 50% inhibition of the induction of the Fra-1 gene. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 26-30 12393186-3 2002 Rapamycin, which binds to FRAP/mTOR and completely suppressed the activation of p70S6 kinase by insulin, almost completely blocked the induction of the hexokinase II gene, and caused an approximately 50% inhibition of the induction of the Fra-1 gene. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 31-35 12515720-6 2003 The mTOR inhibitors rapamycin and CCI-779, the PI3-kinase inhibitor LY294002, and the MEK inhibitor PD98059 all significantly curtailed growth of mutant ras-containing cells. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 4-8 12543789-1 2003 The mTOR inhibitor rapamycin induces G1 cell cycle accumulation and p53-independent apoptosis of the human rhabdomyosarcoma cell line Rh1. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 12234610-6 2002 A molecular mechanism for rapamycin inhibition of mTOR signaling is proposed, in which a putative interaction between PA and mTOR is abolished by rapamycin binding. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 50-54 12234610-6 2002 A molecular mechanism for rapamycin inhibition of mTOR signaling is proposed, in which a putative interaction between PA and mTOR is abolished by rapamycin binding. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 125-129 12351422-3 2002 Rapamycin, an inhibitor of mTOR, is a potent immunosuppressant due, in part, to its ability to interfere with T-cell activation at the level of translation, and it has gained a prominent role in preventing the development and progression of rejection in pancreatic islet transplant recipients. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 12242281-5 2002 Pretreatment of PC-3 cells with the mTOR inhibitor, rapamycin, inhibited both the accumulation of HIF-1alpha and HIF-1-dependent transcription induced by hypoxia or CoCl(2). Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 36-40 12242281-6 2002 Transfection of these cells with wild-type mTOR enhanced HIF-1 activation by hypoxia or CoCl(2), while expression of a rapamycin-resistant mTOR mutant rendered both HIF-1alpha stabilization and HIF-1 transactivating function refractory to inhibition by rapamycin. Sirolimus 119-128 mechanistic target of rapamycin kinase Homo sapiens 139-143 12242281-8 2002 These studies position mTOR as an upstream activator of HIF-1 function in cancer cells and suggest that the antitumor activity of rapamycin is mediated, in part, through the inhibition of cellular responses to hypoxic stress. Sirolimus 130-139 mechanistic target of rapamycin kinase Homo sapiens 23-27 12051762-2 2002 In this study, to investigate whether rapamycin (an mTOR inhibitor) could prevent insulin resistance induced by hyperinsulinemia, 3T3-L1 adipocytes were incubated chronically in the presence of insulin with or without the addition of rapamycin. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 52-56 12039858-8 2002 However, mTOR inhibition by rapamycin specifically abrogated hypoxia-mediated amplification of proliferation and angiogenesis, but was without effect on proliferation under normoxia. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 9-13 11875068-5 2002 Our results show that Delta10mTORrr signals 4E-BP1 and permits rapamycin-treated myoblasts to differentiate, confirming the mTOR dependence of the inhibition of myogenesis by rapamycin. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 29-33 11967149-7 2002 The TOS motif is essential for S6K1 activation by mTOR, as mutations in this motif mimic the effect of rapamycin on S6K1 phosphorylation, and render S6K1 insensitive to changes in amino acids. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 50-54 11847216-1 2002 To determine whether inhibition of either the ribosomal p70 S6 kinase or eukaryotic initiation factor (eIF) 4E pathways downstream of the mammalian target of rapamycin, mTOR, contributes to rapamycin-induced growth arrest, clones of Rh30 rhabdomyosarcoma cells were selected for rapamycin resistance. Sirolimus 158-167 mechanistic target of rapamycin kinase Homo sapiens 169-173 11847216-1 2002 To determine whether inhibition of either the ribosomal p70 S6 kinase or eukaryotic initiation factor (eIF) 4E pathways downstream of the mammalian target of rapamycin, mTOR, contributes to rapamycin-induced growth arrest, clones of Rh30 rhabdomyosarcoma cells were selected for rapamycin resistance. Sirolimus 190-199 mechanistic target of rapamycin kinase Homo sapiens 169-173 11805722-7 2002 SRL disrupts costimulatory and cytokine-stimulated T cell activation by inhibiting a multifunctional kinase, mammalian target of sirolimus (mTOR). Sirolimus 129-138 mechanistic target of rapamycin kinase Homo sapiens 140-144 11909972-8 2002 Rapamycin attenuated caAkt-induced overgrowth of the heart, suggesting that the mammalian target of rapamycin (mTOR) or effectors of mTOR mediated caAkt-induced heart growth. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 80-109 11909972-8 2002 Rapamycin attenuated caAkt-induced overgrowth of the heart, suggesting that the mammalian target of rapamycin (mTOR) or effectors of mTOR mediated caAkt-induced heart growth. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 111-115 11909972-8 2002 Rapamycin attenuated caAkt-induced overgrowth of the heart, suggesting that the mammalian target of rapamycin (mTOR) or effectors of mTOR mediated caAkt-induced heart growth. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 133-137 11799119-5 2002 The TPA-stimulated phosphorylation of all these sites is sensitive to inhibitors of MEK and to the inhibitor of mTOR, rapamycin, indicating that inputs from both mTOR and MEK are required for the regulation of 4E-BP1 phosphorylation by TPA. Sirolimus 118-127 mechanistic target of rapamycin kinase Homo sapiens 112-116 11799119-5 2002 The TPA-stimulated phosphorylation of all these sites is sensitive to inhibitors of MEK and to the inhibitor of mTOR, rapamycin, indicating that inputs from both mTOR and MEK are required for the regulation of 4E-BP1 phosphorylation by TPA. Sirolimus 118-127 mechanistic target of rapamycin kinase Homo sapiens 162-166 11855825-6 2002 The phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin and the mammalian target of rapamycin (mTOR) inhibitor rapamycin, but not the mitogen-activated protein kinase (MAPK)-activating kinase (MEK) inhibitor PD98059, reversed the IGF-1-induced effects observed on eIF-4E/4G assembly and phosphorylation status of 4E-BP1, eIF-4E, and eIF-4G. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 102-106 12489846-8 2002 However, HBC4 cells were sensitized to anoikis when PD98059 was combined with the mTOR inhibitor rapamycin. Sirolimus 97-106 mechanistic target of rapamycin kinase Homo sapiens 82-86 11792863-9 2002 The inhibition by rapamycin was blocked by FK506, which competitively inhibits those effects of rapamycin that are mediated by inhibition of mTOR. Sirolimus 96-105 mechanistic target of rapamycin kinase Homo sapiens 141-145 11756682-9 2002 Disruption of mTOR signaling by rapamycin results in a reduction of late-phase LTP expression induced by high-frequency stimulation; the early phase of LTP is unaffected. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 14-18 11777993-7 2002 Addition of the macrolide, rapamycin, to fibroblast culture medium blocked the up-regulation by GD-IgG of IL-16, implicating the FRAP/mTOR/p70(s6k) pathway in the induction of IL-16 expression. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 129-133 11777993-7 2002 Addition of the macrolide, rapamycin, to fibroblast culture medium blocked the up-regulation by GD-IgG of IL-16, implicating the FRAP/mTOR/p70(s6k) pathway in the induction of IL-16 expression. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 134-138 11948686-2 2002 Inhibition of mTOR with rapamycin resulted in approximately 50% inhibition of the insulin-induced degradation of IRS-1. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 14-18 11825325-6 2001 Since the inhibitory effect of sirolimus disables virtually all responses to cytokine mediators due to the widespread involvement of mTOR in multiple signalling pathways, the agent is likely also to retard proliferation of endothelial and vascular smooth muscle cells, an important component of the immuno-obliterative processes associated with chronic rejection. Sirolimus 31-40 mechanistic target of rapamycin kinase Homo sapiens 133-137 11713299-7 2001 Inhibition of mTOR by rapamycin led to fast and complete repression of S6K1, as judged by rpS6 phosphorylation, but to only partial and delayed repression of translational activation of TOP mRNAs. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 11698435-2 2001 Anti-CTLA-4 mAb treatment during primary Ag exposure increases cell cycle progression and enhances recall Ag responsiveness; however, simultaneous treatment with rapamycin, an inhibitor of the mammalian target of rapamycin and potent antiproliferative agent, prevents both effects. Sirolimus 162-171 mechanistic target of rapamycin kinase Homo sapiens 193-222 11733037-8 2001 The portion of p70beta activity inhibited by rapamycin was rescued by the rapamycin-resistant mutant of the mammalian target of rapamycin (mTOR). Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 108-137 11733037-8 2001 The portion of p70beta activity inhibited by rapamycin was rescued by the rapamycin-resistant mutant of the mammalian target of rapamycin (mTOR). Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 139-143 11715023-4 2001 Furthermore, rapamycin, a selective blocker of mTOR, blocked hypertrophy in all models tested, without causing atrophy in control muscles. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 47-51 11498541-5 2001 The effect of amino acids was fully prevented by the specific mTOR inhibitor rapamycin. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 62-66 11593425-1 2001 Rapamycin, a specific inhibitor of the serine/threonine mTOR kinase, markedly inhibited both cell growth and apoptosis in human B-cell lines. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 56-60 11792863-9 2002 The inhibition by rapamycin was blocked by FK506, which competitively inhibits those effects of rapamycin that are mediated by inhibition of mTOR. Sirolimus 18-27 mechanistic target of rapamycin kinase Homo sapiens 141-145 11573200-7 2001 We conclude that a component of the adipogenic program, operating after the completion of clonal expansion, is inhibited by rapamycin, suggesting an ongoing need for mTOR function in this process. Sirolimus 124-133 mechanistic target of rapamycin kinase Homo sapiens 166-170 11593425-6 2001 It was found that the mTOR kinase was activated in cells treated with taxol or with nocodazole although it was inhibited in cells pre-treated with rapamycin. Sirolimus 147-156 mechanistic target of rapamycin kinase Homo sapiens 22-26 11500364-2 2001 Insulin induces dephosphorylation of eEF2 and inactivation of eEF2 kinase, and these effects are blocked by rapamycin, which inhibits the mammalian target of rapamycin, mTOR. Sirolimus 108-117 mechanistic target of rapamycin kinase Homo sapiens 138-167 11500364-2 2001 Insulin induces dephosphorylation of eEF2 and inactivation of eEF2 kinase, and these effects are blocked by rapamycin, which inhibits the mammalian target of rapamycin, mTOR. Sirolimus 108-117 mechanistic target of rapamycin kinase Homo sapiens 169-173 11352836-8 2001 Treatment with rapamycin, an inhibitor of the p70S6 kinase activator mTOR, also resulted in growth inhibition, further suggesting the importance of the PI3K signaling pathway in AVP-induced proliferation. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 69-73 11438661-1 2001 A pathway sensitive to rapamycin, a selective inhibitor of mammalian target of rapamycin (mTOR), down-regulates effects of insulin such as activation of Akt (protein kinase B) via proteasomal degradation of insulin receptor substrate 1 (IRS-1). Sirolimus 23-32 mechanistic target of rapamycin kinase Homo sapiens 59-88 11438661-1 2001 A pathway sensitive to rapamycin, a selective inhibitor of mammalian target of rapamycin (mTOR), down-regulates effects of insulin such as activation of Akt (protein kinase B) via proteasomal degradation of insulin receptor substrate 1 (IRS-1). Sirolimus 23-32 mechanistic target of rapamycin kinase Homo sapiens 90-94 11287630-8 2001 mTOR induced the serine phosphorylation of IRS-1 (Ser-636/639), and such phosphorylation was inhibited by rapamycin. Sirolimus 106-115 mechanistic target of rapamycin kinase Homo sapiens 0-4 11341787-4 2001 METHODS: Quiescent BxPC3 and Panc-1 human pancreatic cancer cells treated with or without 20 ng/mL rapamycin (FRAP inhibitor) were repleted with 10% FCS to induce cell cycle entry. Sirolimus 99-108 mechanistic target of rapamycin kinase Homo sapiens 110-114 11023817-5 2000 Rapamycin, the inhibitor of mammalian target of rapamycin ("mTOR"), but not PD98059, the inhibitor of extracellular signal-regulated protein kinases ("ERK1/2"), induced similar effects on 4E-BP1 phosphorylation to ischaemia; nevertheless, 4E-BP1-eIF4E complex levels were higher in ischaemia than in rapamycin-treated cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 28-57 11231341-7 2001 Rapamycin abrogated 4E-BP1 phosphorylation in response to insulin, suggesting involvement of mammalian target of rapamycin (mTOR), a kinase downstream of Akt. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 93-122 11231341-7 2001 Rapamycin abrogated 4E-BP1 phosphorylation in response to insulin, suggesting involvement of mammalian target of rapamycin (mTOR), a kinase downstream of Akt. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 124-128 11400101-3 2001 Rapamycin, an mTOR signaling inhibitor, immunosuppressant, and G1-phase arresting agent, was identified and tested for efficacy in restraining cell cycle progression in CRL 1606 hybridoma cultures. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 11054111-9 2000 Consistent with this observation, pretreatment of resting cells with rapamycin suppresses the activation of TOP mRNA translation induced by act D. These results indicate that the effect of act D on translation is mediated by the S6Ks through FRAP/mTOR. Sirolimus 69-78 mechanistic target of rapamycin kinase Homo sapiens 242-246 11054111-9 2000 Consistent with this observation, pretreatment of resting cells with rapamycin suppresses the activation of TOP mRNA translation induced by act D. These results indicate that the effect of act D on translation is mediated by the S6Ks through FRAP/mTOR. Sirolimus 69-78 mechanistic target of rapamycin kinase Homo sapiens 247-251 10971657-5 2000 These deletions also abolished the ability of a rapamycin-resistant mTOR mutant to rescue the activity of p70 alpha from inhibition induced by rapamycin in vivo. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 68-72 10981855-4 2000 Rapamycin, a specific inhibitor of the mammalian target of rapamycin (mTOR), which is an upstream signaling of p70S6K, completely inhibited FCS-induced cell size increases and protein synthesis, but had no effect on SKA mRNA expression. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 39-68 10981855-4 2000 Rapamycin, a specific inhibitor of the mammalian target of rapamycin (mTOR), which is an upstream signaling of p70S6K, completely inhibited FCS-induced cell size increases and protein synthesis, but had no effect on SKA mRNA expression. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 70-74 10660603-5 2000 The FRAP kinase inhibitor rapamycin and the DNA repair inhibitor aphidicolin significantly suppressed the UVB-mediated increase in p70 ribosomal S6 kinase activity by 50-65% and MMP-1 and MMP-3 protein levels by 34-68% and 42-88% compared with UVB-irradiated fibroblasts. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 4-8 10775131-5 2000 Rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), and wortmannin, a phosphatidylinositol 3-kinase inhibitor, blocked flow-induced pp70(S6k) activation; FK-506, a rapamycin analog with minimal mTOR inhibitory activity, and PD-98059, an inhibitor of the flow-sensitive mitogen-activated protein kinase pathway, had no effect. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 31-60 10775131-5 2000 Rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), and wortmannin, a phosphatidylinositol 3-kinase inhibitor, blocked flow-induced pp70(S6k) activation; FK-506, a rapamycin analog with minimal mTOR inhibitory activity, and PD-98059, an inhibitor of the flow-sensitive mitogen-activated protein kinase pathway, had no effect. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 62-66 10775131-5 2000 Rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), and wortmannin, a phosphatidylinositol 3-kinase inhibitor, blocked flow-induced pp70(S6k) activation; FK-506, a rapamycin analog with minimal mTOR inhibitory activity, and PD-98059, an inhibitor of the flow-sensitive mitogen-activated protein kinase pathway, had no effect. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 211-215 10775131-6 2000 Synthesis of Bcl-3, a protein whose translation is controlled by an mTOR-dependent pathway, was induced by flow and inhibited by rapamycin and wortmannin. Sirolimus 129-138 mechanistic target of rapamycin kinase Homo sapiens 68-72 10753934-2 2000 All these effects were blocked by rapamycin, a specific inhibitor of mTOR. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 69-73 10749120-4 2000 LY294002 and rapamycin also inhibit growth factor- and mitogen-induced secretion of vascular endothelial growth factor, the product of a known HIF-1 target gene, thus linking the PI3K/PTEN/AKT/FRAP pathway, HIF-1, and tumor angiogenesis. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 193-197 10567431-3 1999 We report here that a mammalian recombinant p70alpha polypeptide, extracted in an inactive form from rapamycin-treated cells, can be directly phosphorylated by the mTOR kinase in vitro predominantly at the rapamycin-sensitive site Thr-412. Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 164-168 10660304-5 2000 We found that CNTF-induced phosphorylation of Ser727 was inhibited by the mTOR inhibitor rapamycin, but not by inhibitors of MAPK and protein kinase C (PKC) activation. Sirolimus 89-98 mechanistic target of rapamycin kinase Homo sapiens 74-78 10574945-7 1999 Phosphorylation at the Ser-662 site is independently controlled by a pathway involving mammalian TOR (mTOR) because the rapamycin-induced block of its phosphorylation is overcome by co-expression of a rapamycin-resistant mutant of mTOR. Sirolimus 120-129 mechanistic target of rapamycin kinase Homo sapiens 102-106 10574945-7 1999 Phosphorylation at the Ser-662 site is independently controlled by a pathway involving mammalian TOR (mTOR) because the rapamycin-induced block of its phosphorylation is overcome by co-expression of a rapamycin-resistant mutant of mTOR. Sirolimus 120-129 mechanistic target of rapamycin kinase Homo sapiens 231-235 10716639-4 2000 Rapamycin kills normal cells more readily in normal than in A-T cells, and inhibits the FRAP target p70 S6 kinase (p70S6K) more readily in normal than in A-T cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 88-92 10567431-3 1999 We report here that a mammalian recombinant p70alpha polypeptide, extracted in an inactive form from rapamycin-treated cells, can be directly phosphorylated by the mTOR kinase in vitro predominantly at the rapamycin-sensitive site Thr-412. Sirolimus 206-215 mechanistic target of rapamycin kinase Homo sapiens 164-168 10551813-4 1999 Further characterization of ROS-induced activation of p70(S6k) using specific inhibitors for p70(S6k) signaling pathway, rapamycin, and wortmannin revealed that ROS acted upstream of the rapamycin-sensitive component FRAP/RAFT and wortmannin-sensitive component phosphatidylinositol 3-kinase, because both inhibitors caused the inhibition of ROS-induced p70(S6k) activity. Sirolimus 121-130 mechanistic target of rapamycin kinase Homo sapiens 217-221 10318894-2 1999 We describe a dominant clonal-selection assay of stably transfected cells expressing partner proteins FKBP (FK506 binding protein) and FRAP (FKBP-rapamycin binding protein) fused to DHFR fragments and show a rapamycin dose-dependent survival of clones that requires approximately 25 molecules of reconstituted DHFR per cell. Sirolimus 146-155 mechanistic target of rapamycin kinase Homo sapiens 135-139 10490847-1 1999 Rapamycin is an immunosuppressant which antagonizes cellular proliferation by inhibiting the function of mTOR. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 105-109 10499523-10 1999 Furthermore, rapamycin, a selective inhibitor of mammalian target of rapamycin, completely blocked ET-1-stimulated [3H]leucine and [3H]thymidine uptake. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 49-78 10446965-2 1999 Treatment of cells with rapamycin, a selective FRAP Inhibitor, inhibited basal p70s6K kinase activity and induced dephosphorylation of p70s6K and 4E-BP1. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 47-51 10330171-4 1999 Phosphorylation of the 4E-BPs is effected by the phosphatidylinositol (PI) 3-kinase signal transduction pathway and is inhibited by rapamycin through its binding to FRAP/mTOR (FK506 binding protein-rapamycin-associated protein or mammalian target of rapamycin). Sirolimus 132-141 mechanistic target of rapamycin kinase Homo sapiens 170-174 10359590-6 1999 Similarly, inhibition of the PI3K-mTOR pathway by addition of the PI3K inhibitor 2-[4-morpholinyl]-8-phenyl-4H-1-benzopyran-4-one (LY294002) or the mTOR inhibitor rapamycin, although reducing several parameters of transformation, also failed to block transformation. Sirolimus 163-172 mechanistic target of rapamycin kinase Homo sapiens 34-38 10200280-7 1999 FRAP also is shown to phosphorylate PP2A in vitro, consistent with a model in which phosphorylation of PP2A by FRAP prevents the dephosphorylation of 4E-BP1 and p70(s6k), whereas amino acid deprivation or rapamycin treatment inhibits FRAP"s ability to restrain the phosphatase. Sirolimus 205-214 mechanistic target of rapamycin kinase Homo sapiens 111-115 10206976-9 1999 Rapamycin, an inhibitor of the protein kinase mTOR, prevented all of the leucine-induced effects. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 46-50 10200280-2 1999 Depriving cells of amino acids or treating them with the small molecule rapamycin inhibits FRAP and results in rapid dephosphorylation and inactivation of the translational regulators 4E-BP1(eukaryotic initiation factor 4E-binding protein 1) and p70(s6k) (the 70-kDa S6 kinase). Sirolimus 72-81 mechanistic target of rapamycin kinase Homo sapiens 91-95 10200280-7 1999 FRAP also is shown to phosphorylate PP2A in vitro, consistent with a model in which phosphorylation of PP2A by FRAP prevents the dephosphorylation of 4E-BP1 and p70(s6k), whereas amino acid deprivation or rapamycin treatment inhibits FRAP"s ability to restrain the phosphatase. Sirolimus 205-214 mechanistic target of rapamycin kinase Homo sapiens 0-4 10200280-7 1999 FRAP also is shown to phosphorylate PP2A in vitro, consistent with a model in which phosphorylation of PP2A by FRAP prevents the dephosphorylation of 4E-BP1 and p70(s6k), whereas amino acid deprivation or rapamycin treatment inhibits FRAP"s ability to restrain the phosphatase. Sirolimus 205-214 mechanistic target of rapamycin kinase Homo sapiens 111-115 10092613-7 1999 Finally, the negative regulatory effects of PDGF and Akt were inhibited by rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), one of the downstream targets of Akt. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 106-135 10092613-7 1999 Finally, the negative regulatory effects of PDGF and Akt were inhibited by rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), one of the downstream targets of Akt. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 137-141 9792703-7 1998 PI 3-kinase inhibitors such as wortmannin and LY294002, and rapamycin, an inhibitor of FRAP/TOR, cause a decline in the level of D-cyclins, whereas inhibitors of mitogen-activated protein kinase kinase and farnesyltransferase do not. Sirolimus 60-69 mechanistic target of rapamycin kinase Homo sapiens 87-91 10029080-0 1999 Rapamycin causes poorly reversible inhibition of mTOR and induces p53-independent apoptosis in human rhabdomyosarcoma cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 49-53 10029080-3 1999 Here, we report that rapamycin, a specific inhibitor of mTOR kinase, induces G1 cell cycle arrest and apoptosis in two rhabdomyosarcoma cell lines (Rh1 and Rh30) under conditions of autocrine cell growth. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 56-60 10029080-9 1999 Rh1 and Rh30 mTOR-rr clones were highly resistant (>3000-fold) to both growth inhibition and apoptosis induced by rapamycin. Sirolimus 117-126 mechanistic target of rapamycin kinase Homo sapiens 13-17 9852118-1 1998 Incubating 3T3-L1 adipocytes with forskolin, which increases intracellular cAMP by activating adenylate cyclase, mimicked rapamycin by attenuating the effect of insulin on stimulating the phosphorylation of four (S/T)P sites in PHAS-I, a downstream target of the mammalian target of rapamycin (mTOR) signaling pathway. Sirolimus 122-131 mechanistic target of rapamycin kinase Homo sapiens 263-292 9852118-1 1998 Incubating 3T3-L1 adipocytes with forskolin, which increases intracellular cAMP by activating adenylate cyclase, mimicked rapamycin by attenuating the effect of insulin on stimulating the phosphorylation of four (S/T)P sites in PHAS-I, a downstream target of the mammalian target of rapamycin (mTOR) signaling pathway. Sirolimus 122-131 mechanistic target of rapamycin kinase Homo sapiens 294-298 9722592-9 1998 Phosphorylation of p70 S6 kinase and 4E-BP1 is also repressed by PI3K inhibitors as well as by rapamycin, the selective inhibitor of FRAP/mTOR. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 133-137 9722592-9 1998 Phosphorylation of p70 S6 kinase and 4E-BP1 is also repressed by PI3K inhibitors as well as by rapamycin, the selective inhibitor of FRAP/mTOR. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 138-142 9621041-1 1998 Inhibitors of the phosphatidylinositol 3-kinase (PI3 kinase)-FKBP-rapamycin-associated protein (FRAP) pathway, such as rapamycin and wortmannin, induce dephosphorylation and activation of the suppressor of cap-dependent translation, 4E-BP1. Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 96-100 9636226-4 1998 Insulin also increased by severalfold the 32P content of mTOR that was determined after purifying the protein from 32P-labeled adipocytes with rapamycin.FKBP12 agarose beads. Sirolimus 143-152 mechanistic target of rapamycin kinase Homo sapiens 57-61 9249059-1 1997 The role of phosphatidylinositol 3-kinase and FK506-binding protein rapamycin-associated protein (FRAP) in translational control has been examined by treating RD-rhabdomyosarcoma cells with wortmannin and rapamycin and studying the effects on cell-growth, translation initiation, and protein synthesis. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 98-102 9434772-4 1997 Protein kinase activity directed towards mTOR was tightly associated with mTOR immunoprecipitates and this kinase activity was inhibited by FKBP12-rapamycin indicating it was due to an autokinase activity present in mTOR. Sirolimus 147-156 mechanistic target of rapamycin kinase Homo sapiens 41-45 9434772-4 1997 Protein kinase activity directed towards mTOR was tightly associated with mTOR immunoprecipitates and this kinase activity was inhibited by FKBP12-rapamycin indicating it was due to an autokinase activity present in mTOR. Sirolimus 147-156 mechanistic target of rapamycin kinase Homo sapiens 74-78 9434772-4 1997 Protein kinase activity directed towards mTOR was tightly associated with mTOR immunoprecipitates and this kinase activity was inhibited by FKBP12-rapamycin indicating it was due to an autokinase activity present in mTOR. Sirolimus 147-156 mechanistic target of rapamycin kinase Homo sapiens 74-78 9334222-2 1997 Previous work has established that the protein known as mTOR/RAFT-1/FRAP is the target through which the rapamycin.FKBP12 complex acts to dephosphorylate/deactivate the p70 S6 kinase; thus, some mTOR mutants that have lost the ability to bind to the rapamycin.FKBP12 complex in vitro can protect the p70 S6 kinase against rapamycin-induced dephosphorylation/deactivation in situ. Sirolimus 105-114 mechanistic target of rapamycin kinase Homo sapiens 56-60 9334222-2 1997 Previous work has established that the protein known as mTOR/RAFT-1/FRAP is the target through which the rapamycin.FKBP12 complex acts to dephosphorylate/deactivate the p70 S6 kinase; thus, some mTOR mutants that have lost the ability to bind to the rapamycin.FKBP12 complex in vitro can protect the p70 S6 kinase against rapamycin-induced dephosphorylation/deactivation in situ. Sirolimus 105-114 mechanistic target of rapamycin kinase Homo sapiens 61-67 9334222-2 1997 Previous work has established that the protein known as mTOR/RAFT-1/FRAP is the target through which the rapamycin.FKBP12 complex acts to dephosphorylate/deactivate the p70 S6 kinase; thus, some mTOR mutants that have lost the ability to bind to the rapamycin.FKBP12 complex in vitro can protect the p70 S6 kinase against rapamycin-induced dephosphorylation/deactivation in situ. Sirolimus 105-114 mechanistic target of rapamycin kinase Homo sapiens 68-72 9334222-2 1997 Previous work has established that the protein known as mTOR/RAFT-1/FRAP is the target through which the rapamycin.FKBP12 complex acts to dephosphorylate/deactivate the p70 S6 kinase; thus, some mTOR mutants that have lost the ability to bind to the rapamycin.FKBP12 complex in vitro can protect the p70 S6 kinase against rapamycin-induced dephosphorylation/deactivation in situ. Sirolimus 105-114 mechanistic target of rapamycin kinase Homo sapiens 195-199 9334222-3 1997 We show herein that such mTOR mutants also protect eIF-4E BP1 against rapamycin-induced dephosphorylation, and for both p70 S6 kinase and eIF-4E BP1, such protection requires that the rapamycin-resistant mTOR variant retains an active catalytic domain. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 25-29 9334222-3 1997 We show herein that such mTOR mutants also protect eIF-4E BP1 against rapamycin-induced dephosphorylation, and for both p70 S6 kinase and eIF-4E BP1, such protection requires that the rapamycin-resistant mTOR variant retains an active catalytic domain. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 204-208 8662507-1 1996 Rapamycin, a potent immunosuppressive agent, binds two proteins: the FK506-binding protein (FKBP12) and the FKBP-rapamycin-associated protein (FRAP). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 108-141 8662507-1 1996 Rapamycin, a potent immunosuppressive agent, binds two proteins: the FK506-binding protein (FKBP12) and the FKBP-rapamycin-associated protein (FRAP). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 143-147 8595879-6 1996 Moreover, TOR2-RAFT1 and TOR1-RAFT1 hybrid proteins mutated at the position corresponding to rapamycin-resistant TOR mutants (S20351) conferred rapamycin resistance. Sirolimus 93-102 mechanistic target of rapamycin kinase Homo sapiens 30-35 7673106-6 1995 Thus, it is likely that, in vivo, rapamycin does not directly inhibit the PI 4-kinase activity and affects the RAFT1/FRAP protein through another mechanism. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 111-116 7673106-6 1995 Thus, it is likely that, in vivo, rapamycin does not directly inhibit the PI 4-kinase activity and affects the RAFT1/FRAP protein through another mechanism. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 117-121 9383417-2 1995 In the case of FK506, ascomycin and cyclosporin, the target of the immunophilin-immunosuppressant complex is calcineurin; in the case of rapamycin, the target is FRAP (TOR/RAFT1). Sirolimus 137-146 mechanistic target of rapamycin kinase Homo sapiens 162-166 7518356-5 1994 Sequences (330 amino acids total) of tryptic peptides derived from the 245 kDa RAFT1 reveal striking homologies to the yeast TOR gene products, which were originally identified by mutations that confer rapamycin resistance in yeast. Sirolimus 202-211 mechanistic target of rapamycin kinase Homo sapiens 79-84 33971279-1 2021 Inhibition of the mammalian target of rapamycin (mTOR) by rapamycin attenuates heart failure (HF) and age-associated changes in left ventricular (LV) function. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 49-53 33971279-2 2021 Rapamycin has also been suggested as a therapy for pulmonary hypertension (PH) and concomitant right heart failure (PH-RHF) based on reports of elevated mTOR signaling in young models with PH. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 153-157 33797919-3 2021 In this study, we used stable isotope labeling of amino acids in cell culture with a two-step strategy for phosphopeptide enrichment and high-throughput quantitative mass spectrometry to perform a global phosphoproteome analysis of mTOR inhibition by rapamycin. Sirolimus 251-260 mechanistic target of rapamycin kinase Homo sapiens 232-236 33797919-4 2021 By monitoring the phosphoproteome alterations upon rapamycin treatment, downregulation of mTOR signaling pathway was detected and enriched. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 90-94 33816275-7 2021 Mechanistically, NRBP2 regulated the activation of the 5"-adenosine monophosphate (AMP)-activated protein kinase/ mammalian target of rapamycin (AMPK/mTOR) signaling pathway. Sirolimus 134-143 mechanistic target of rapamycin kinase Homo sapiens 150-154 33797919-9 2021 In conclusion, we presented a high-confidence phosphoproteome map inside the cells upon mTOR inhibition by rapamycin. Sirolimus 107-116 mechanistic target of rapamycin kinase Homo sapiens 88-92 33773987-7 2021 Withdrawal of sirolimus from TSC2-/- cells resulted in a highly proliferative phenotype and caused cells to enter the S-phase of the cell cycle, with persistent phosphorylation of mTOR, p70 S6 kinase, ribosomal protein S6, and 4EBP1, decreased cyclin D kinase inhibitors and transient hyperactivation of Akt. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 180-184 33800526-10 2021 Additionally, co-treatment with OxyR with rapamycin intended to inhibit the mammalian target of rapamycin (mTOR) caused significantly lower levels of phospho-S6 ribosomal protein (pS6) and higher LC3-II expression, implying that OxyR-mediated autophagy was dependent on the mTOR pathway. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 76-105 33800526-10 2021 Additionally, co-treatment with OxyR with rapamycin intended to inhibit the mammalian target of rapamycin (mTOR) caused significantly lower levels of phospho-S6 ribosomal protein (pS6) and higher LC3-II expression, implying that OxyR-mediated autophagy was dependent on the mTOR pathway. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 107-111 33800526-10 2021 Additionally, co-treatment with OxyR with rapamycin intended to inhibit the mammalian target of rapamycin (mTOR) caused significantly lower levels of phospho-S6 ribosomal protein (pS6) and higher LC3-II expression, implying that OxyR-mediated autophagy was dependent on the mTOR pathway. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 274-278 33034924-5 2021 This effect was dependent on protein kinase B/mechanistic target of rapamycin (mTOR)/ p70 S6 Kinase signaling. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 79-83 32889867-3 2020 Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. Sirolimus 130-139 mechanistic target of rapamycin kinase Homo sapiens 77-106 32889867-3 2020 Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. Sirolimus 130-139 mechanistic target of rapamycin kinase Homo sapiens 108-112 32889867-10 2020 CONCLUSIONS: mTOR-inhibitor treatment with sirolimus for >=3 months improves outcomes in LT for HCC, especially in patients with AFP-evidence of higher tumor activity, advocating particularly for mTOR inhibitor use in this subgroup of patients. Sirolimus 43-52 mechanistic target of rapamycin kinase Homo sapiens 13-17 32796405-7 2020 Furthermore, UBE2T appears to exert its effects via the mammalian target of rapamycin (mTOR) pathway as the cellular effects caused by UBE2T overexpression are inhibited by the mTOR inhibitor rapamycin. Sirolimus 76-85 mechanistic target of rapamycin kinase Homo sapiens 87-91 32796405-7 2020 Furthermore, UBE2T appears to exert its effects via the mammalian target of rapamycin (mTOR) pathway as the cellular effects caused by UBE2T overexpression are inhibited by the mTOR inhibitor rapamycin. Sirolimus 76-85 mechanistic target of rapamycin kinase Homo sapiens 177-181 32796887-2 2020 Mammalian target of rapamycin complex 1 (mTORC1), a protein complex that contains the serine-threonine kinase mTOR, mediates signaling that underlies the control of cellular functions such as proliferation and autophagy by various external stimuli. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 41-45 34191518-5 2022 Our studies showed that WRX606 formed a ternary complex with FK506-binding protein-12 (FKBP12) and FKBP-rapamycin-binding (FRB) domain of mTOR, resulting in the allosteric inhibition of mTORC1. Sirolimus 104-113 mechanistic target of rapamycin kinase Homo sapiens 138-142 17360108-0 2007 An activated mTOR/p70S6K signaling pathway in esophageal squamous cell carcinoma cell lines and inhibition of the pathway by rapamycin and siRNA against mTOR. Sirolimus 125-134 mechanistic target of rapamycin kinase Homo sapiens 13-17 17360108-0 2007 An activated mTOR/p70S6K signaling pathway in esophageal squamous cell carcinoma cell lines and inhibition of the pathway by rapamycin and siRNA against mTOR. Sirolimus 125-134 mechanistic target of rapamycin kinase Homo sapiens 153-157 15894895-10 2005 Treatment with 6 nmol/l rapamycin partly antagonized the effect of DMSO, indicating the involvement of mTOR in regulation of the smooth muscle phenotype of MSCs. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 103-107 34902358-5 2022 We determined that the knockdown of Maf1 promoted the survival of RGCs and their axon regeneration through altering the activity of the PTEN/mTOR pathway, which could be blocked by rapamycin. Sirolimus 181-190 mechanistic target of rapamycin kinase Homo sapiens 141-145 23997112-7 2013 Stimulation of mammalian target of rapamycin (mTOR)-dependent signaling protected against cell death induced by paraquat, whereas MPP+-induced toxicity was enhanced by wortmannin, a phosphoinositide 3-kinase class III inhibitor, rapamycin, and trehalose, an mTOR-independent autophagy activator. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 46-50 23888043-1 2013 The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) protein kinase promotes growth and is the target of rapamycin, a clinically useful drug that also prolongs life span in model organisms. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 37-41 34847519-2 2022 Rapamycin is a specific natural inhibitor of the mechanistic target of rapamycin (mTOR) that is a kinase protein playing a pivotal role in cell growth and proliferation by activation of several metabolic processes. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 49-80 34847519-2 2022 Rapamycin is a specific natural inhibitor of the mechanistic target of rapamycin (mTOR) that is a kinase protein playing a pivotal role in cell growth and proliferation by activation of several metabolic processes. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 82-86 34959190-8 2022 In addition, treatment with rapamycin, an inhibitor of mTOR, reversed the SKBR3-TR-induced promotion of tube formation. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 55-59 34839054-1 2022 A phase II study was conducted to ascertain whether sequential exposure to decitabine followed by rapamycin, an mTOR (mechanistic target of rapamycin) inhibitor would result in better responses than decitabine alone. Sirolimus 98-107 mechanistic target of rapamycin kinase Homo sapiens 112-116 34619135-7 2022 Inhibiting mTOR activity with rapamycin induces raptor and restores AKT activity, allowing beta-cells to gain proliferation capacity that are lost after HFD exposure. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 11-15 34748756-6 2022 The observed effects of Gpc4 on MFS were significantly antagonized when mice were treated with L-leucine or rapamycin, an agonist or antagonist of the mammalian target of rapamycin (mTOR) signal, respectively, demonstrating that mTOR pathway is an essential requirement for Gpc4-regulated MFS. Sirolimus 108-117 mechanistic target of rapamycin kinase Homo sapiens 151-180 34748756-6 2022 The observed effects of Gpc4 on MFS were significantly antagonized when mice were treated with L-leucine or rapamycin, an agonist or antagonist of the mammalian target of rapamycin (mTOR) signal, respectively, demonstrating that mTOR pathway is an essential requirement for Gpc4-regulated MFS. Sirolimus 108-117 mechanistic target of rapamycin kinase Homo sapiens 182-186 34748756-6 2022 The observed effects of Gpc4 on MFS were significantly antagonized when mice were treated with L-leucine or rapamycin, an agonist or antagonist of the mammalian target of rapamycin (mTOR) signal, respectively, demonstrating that mTOR pathway is an essential requirement for Gpc4-regulated MFS. Sirolimus 108-117 mechanistic target of rapamycin kinase Homo sapiens 229-233 34797524-12 2022 Accordingly, the in vivo and in vitro experiments revealed that the mTOR inhibitor rapamycin further increased cell mortality and exhibited enhanced antitumor effect on GBM cells when co-treated with the ERK inhibitor. Sirolimus 83-92 mechanistic target of rapamycin kinase Homo sapiens 68-72 34304300-3 2022 We report our experience of using sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, in the treatment of CHI in seven newborns who are poorly responding to standard medical therapy. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 47-76 34304300-3 2022 We report our experience of using sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, in the treatment of CHI in seven newborns who are poorly responding to standard medical therapy. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 78-82 34304300-9 2022 Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, was recently reported to be useful for refractory CHI cases with variable efficacy. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 13-42 34304300-9 2022 Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, was recently reported to be useful for refractory CHI cases with variable efficacy. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 44-48 34839054-1 2022 A phase II study was conducted to ascertain whether sequential exposure to decitabine followed by rapamycin, an mTOR (mechanistic target of rapamycin) inhibitor would result in better responses than decitabine alone. Sirolimus 98-107 mechanistic target of rapamycin kinase Homo sapiens 118-149 34965300-2 2022 The mTOR inhibitor Rapamycin (RAPA) is used as an immunosuppressive agent in patients with organ transplants and other immunological disorders; and it also has anti-tumorigenic potential. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 34739690-0 2022 Hormetic effect of low doses of rapamycin triggers anti-aging cascades in WRL-68 cells by modulating an mTOR-mitochondria cross-talk. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 104-108 34739690-5 2022 Although previous studies have suggested that hormetic (low) doses of rapamycin can cause partial/incomplete inhibition of mTOR, the actual modus operandi of how such partial mTOR inhibition might modulate the mTOR-mitochondria cross-talk remained to be deciphered in the context of cellular aging. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 123-127 34739690-5 2022 Although previous studies have suggested that hormetic (low) doses of rapamycin can cause partial/incomplete inhibition of mTOR, the actual modus operandi of how such partial mTOR inhibition might modulate the mTOR-mitochondria cross-talk remained to be deciphered in the context of cellular aging. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 175-179 34739690-5 2022 Although previous studies have suggested that hormetic (low) doses of rapamycin can cause partial/incomplete inhibition of mTOR, the actual modus operandi of how such partial mTOR inhibition might modulate the mTOR-mitochondria cross-talk remained to be deciphered in the context of cellular aging. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 210-214 34739690-11 2022 CONCLUSIONS: We established that low doses of rapamycin can hormetically amend the mTOR-mitochondria cross-talk, and can consequently promote anti-aging outcome in cells. Sirolimus 46-55 mechanistic target of rapamycin kinase Homo sapiens 83-87 34662660-9 2022 These effects of LicA were restored or suppressed by mTOR inhibitor rapamycin or PI3K inhibitor LY294002. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 53-57 34965300-2 2022 The mTOR inhibitor Rapamycin (RAPA) is used as an immunosuppressive agent in patients with organ transplants and other immunological disorders; and it also has anti-tumorigenic potential. Sirolimus 30-34 mechanistic target of rapamycin kinase Homo sapiens 4-8 34961940-6 2022 Direct suppression of mTOR activity by rapamycin selectively impaired IL-10 production by B cells whereas secretion was restored upon GSK3 inhibition. Sirolimus 39-48 mechanistic target of rapamycin kinase Homo sapiens 22-26 34983907-3 2022 Increasing evidence shows that mTOR also regulates VSMC proliferation in vascular proliferative diseases and that mTOR inhibitors, such as rapamycin, effectively restrain VSMC proliferation. Sirolimus 139-148 mechanistic target of rapamycin kinase Homo sapiens 114-118 34983907-3 2022 Increasing evidence shows that mTOR also regulates VSMC proliferation in vascular proliferative diseases and that mTOR inhibitors, such as rapamycin, effectively restrain VSMC proliferation. Sirolimus 139-148 mechanistic target of rapamycin kinase Homo sapiens 31-35 34987517-8 2021 Blockade of the pathway with mTOR inhibitor sirolimus not only inhibits tumor growth but also suppresses the T cell infiltration in colitic lesions. Sirolimus 44-53 mechanistic target of rapamycin kinase Homo sapiens 29-33 34936813-0 2022 Mammalian Target of Rapamycin Inhibitor Rapamycin Alleviates 7-Ketocholesterol Induced Inflammatory Responses and Vascular Endothelial Growth Factor Elevation by Regulating MAPK Pathway in Human Retinal Pigment Epithelium Cells. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 0-29 34970878-1 2021 OBJECTIVE: To observe the effect of acupuncture of "Yinlingquan"(SP9) and "Sanyinjiao"(SP6) on expression of phosphatidylinositol-3 kinase/protein kinase B/mammalian target protein of rapamycin (PI3K/Akt/mTOR) signaling in adjuvant arthritis (AA) rats, so as to explore its mechanism underlying improvement of AA. Sirolimus 184-193 mechanistic target of rapamycin kinase Homo sapiens 204-208 34936813-8 2022 mTOR inhibitor rapamycin significantly suppressed the elevation of IL-6, IL-8, and VEGF stimulated by 7-KC. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 0-4 34936813-9 2022 Rapamycin not only decreased the level of phosphorylated mTOR, P70S6K, 4EBP1 but also inhibited the activation of MAPK pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 57-61 34931134-6 2021 Further inhibition of PI3K signaling, using LY294002, or of mTOR, by rapamycin, blocked the migration and invasion of UM cells similarly to artemisinin. Sirolimus 69-78 mechanistic target of rapamycin kinase Homo sapiens 60-64 34944711-11 2021 Finally, the treatment with mTOR inhibitor rapamycin predominantly reduced the formation of autophagy and ultimately mitigated the cellular migration ability of ccRCC cells with LTF knockdown. Sirolimus 43-52 mechanistic target of rapamycin kinase Homo sapiens 28-32 34924000-11 2021 Lastly, the PI3K/AKT/mTOR pathway both in fractured osteoblasts and femurs was inhibited by rapamycin and beta-ecdysterone. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 21-25 34919773-1 2022 BACKGROUND: The effects of mammalian target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) on survival in liver transplantation (LT) recipients with hepatocellular carcinoma (HCC) remain the subject of intense research. Sirolimus 76-85 mechanistic target of rapamycin kinase Homo sapiens 27-56 34919773-1 2022 BACKGROUND: The effects of mammalian target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) on survival in liver transplantation (LT) recipients with hepatocellular carcinoma (HCC) remain the subject of intense research. Sirolimus 76-85 mechanistic target of rapamycin kinase Homo sapiens 58-62 34813306-8 2021 The combination treatment of BDMC and rapamycin enhanced the inhibition of TNBC proliferation and metastasis through increasing the blockage of mTOR activation. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 144-148 34876569-12 2021 In addition, the enhanced sensitivity was partially diminished by rapamycin-mediated inhibition of mTOR in TTK knockdown cells. Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 99-103 34718162-6 2021 Clinical trials in SLE patients have provided preliminary evidence that mTOR blockade by sirolimus (rapamycin) can reverse pro-inflammatory lineage skewing, including the expansion of Th17 and double-negative T cells and plasma cells and the contraction of regulatory T cells. Sirolimus 89-98 mechanistic target of rapamycin kinase Homo sapiens 72-76 34943047-0 2021 mTOR Inhibition via Rapamycin Treatment Partially Reverts the Deficit in Energy Metabolism Caused by FH Loss in RPE Cells. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 0-4 34943047-8 2021 We found that silencing of CFH results in hyperactivation of mTOR signaling along with decreased mitochondrial respiration and that mTOR inhibition via rapamycin can partially rescue these metabolic defects. Sirolimus 152-161 mechanistic target of rapamycin kinase Homo sapiens 132-136 34899911-10 2021 Furthermore, PC4 mediated lung adenocarcinoma cell sensitivity to the HIF-PH inhibitor DMOG and the mTOR inhibitor rapamycin, and PC4 mediated the synergistic effect of DMOG and cisplatin. Sirolimus 115-124 mechanistic target of rapamycin kinase Homo sapiens 100-104 34585990-9 2021 Mechanistically, IL-23 induced EMT was mTOR/S6 signaling dependent and reversible by rapamycin. Sirolimus 85-94 mechanistic target of rapamycin kinase Homo sapiens 39-43 34718162-6 2021 Clinical trials in SLE patients have provided preliminary evidence that mTOR blockade by sirolimus (rapamycin) can reverse pro-inflammatory lineage skewing, including the expansion of Th17 and double-negative T cells and plasma cells and the contraction of regulatory T cells. Sirolimus 100-109 mechanistic target of rapamycin kinase Homo sapiens 72-76 34718162-7 2021 Moreover, sirolimus has shown promising efficacy in the treatment of refractory idiopathic multicentric Castleman disease, newly characterized by systemic autoimmunity due to mTOR overactivation. Sirolimus 10-19 mechanistic target of rapamycin kinase Homo sapiens 175-179 34700229-0 2021 Rapamycin attenuates PLA2R activation-mediated podocyte apoptosis via the PI3K/AKT/mTOR pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 83-87 34859624-1 2021 OBJECTIVES: To study the effects of 17beta-estradiol (E2) on the regulation of the proliferation of condylar chondrocytes and provide a preliminary discussion on the role of phosphorylate-mammalian target of rapamycin (p-mTOR) in this regulatory process. Sirolimus 208-217 mechanistic target of rapamycin kinase Homo sapiens 221-225 34607803-7 2021 Prior work shows that mammalian target of rapamycin (mTOR) inhibitor, rapamycin, induces the proliferation and effector function of gammadelta T cells. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 22-51 34607803-7 2021 Prior work shows that mammalian target of rapamycin (mTOR) inhibitor, rapamycin, induces the proliferation and effector function of gammadelta T cells. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 53-57 34274968-10 2021 The inhibition of MAPK signaling by the ERK1/ERK2 inhibitor and mTOR signaling by rapamycin abrogated the miR-592-mediated upregulation of neuronal differentiation-related genes. Sirolimus 82-91 mechanistic target of rapamycin kinase Homo sapiens 64-68 34888748-11 2021 Furthermore, the rescue assay exhibited that the mTOR inhibitor rapamycin significantly reversed the promoting effect of NUP37 in cell proliferation, migration, and invasion. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 49-53 34624607-3 2021 The mechanistic target of rapamycin inhibitors everolimus and sirolimus have shown to be effective treatments for multiple conditions. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 4-35 34847842-11 2021 The officially accepted mTOR inhibitors that have undergone clinical testing are sirolimus, everolimus, temsirolimus, and tacrolimus. Sirolimus 81-90 mechanistic target of rapamycin kinase Homo sapiens 24-28 34580903-7 2021 The patient responded well to targeted therapy with sirolimus, an mTOR inhibitor. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 66-70 34637337-2 2021 To our knowledge, this phase II, single-arm, registration trial is the first prospective clinical trial in this disease, investigating the safety and efficacy of the mammalian target of rapamycin inhibitor nab-sirolimus (AMPECT, NCT02494570). Sirolimus 210-219 mechanistic target of rapamycin kinase Homo sapiens 166-195 34765012-8 2021 We also found that QYLGT had the ability to activate phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of the rapamycin (mTOR) pathway. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 125-129 34858182-6 2021 Phosphorylation of both PDGFRalpha and PDGFRbeta was increased in hPASMCs after treatment with rapamycin for 48 and 72 h. Based on co-immunoprecipitation studies, longer exposure to rapamycin (24-72 h) significantly inhibited the binding of mTOR to Rictor, mechanistically suggesting mTORC2 inhibition by rapamycin. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 241-245 34858182-6 2021 Phosphorylation of both PDGFRalpha and PDGFRbeta was increased in hPASMCs after treatment with rapamycin for 48 and 72 h. Based on co-immunoprecipitation studies, longer exposure to rapamycin (24-72 h) significantly inhibited the binding of mTOR to Rictor, mechanistically suggesting mTORC2 inhibition by rapamycin. Sirolimus 182-191 mechanistic target of rapamycin kinase Homo sapiens 241-245 34858182-6 2021 Phosphorylation of both PDGFRalpha and PDGFRbeta was increased in hPASMCs after treatment with rapamycin for 48 and 72 h. Based on co-immunoprecipitation studies, longer exposure to rapamycin (24-72 h) significantly inhibited the binding of mTOR to Rictor, mechanistically suggesting mTORC2 inhibition by rapamycin. Sirolimus 305-314 mechanistic target of rapamycin kinase Homo sapiens 241-245 34765012-9 2021 Treatment with PI3K inhibitors, LY294002 and wortmannin, or mTOR inhibitors, rapamycin and Torin 1, could not only recover QYLGT-inhibited cell viability of NPC cells but also inhibit Atg3 expression. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 60-64 34099592-3 2021 Pharmacological inhibitors of mTOR, such as rapamycin and Torin2, markedly suppressed the mRNA level as well as the protein level of HMMR in LNCaP and PC-3 cells. Sirolimus 44-53 mechanistic target of rapamycin kinase Homo sapiens 30-34 34099592-8 2021 Furthermore, the upregulation of HMMR by DHT was abolished by stimulation with rapamycin, prior to DHT treatment, suggesting that mTOR activity is required for the induction of HMMR expression by androgen. Sirolimus 79-88 mechanistic target of rapamycin kinase Homo sapiens 130-134 34560177-11 2021 We detected the changes in autophagy marker protein LC3-II and lipid accumulation using an AKT inhibitor ARQ-092 or a mTOR inhibitor rapamycin in HepG2 cells. Sirolimus 133-142 mechanistic target of rapamycin kinase Homo sapiens 118-122 34757123-6 2022 The mTOR inhibitor, rapamycin, completely abolished activation of mTORC1 and mTORC2 after long term treatment with receptor antibodies. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 4-8 34534609-5 2021 The enhancement of H2S donors on autophagic flux was mediated by adenosine 5"-monophosphate-activated protein kinase (AMPK)-dependent mammalian target of rapamycin (mTOR) inhibition, as H2S donors activated AMPK but reduced the mTOR activity and H2S donors-induced LC3-II increase was diminished by mTOR activator. Sirolimus 154-163 mechanistic target of rapamycin kinase Homo sapiens 165-169 34669157-3 2021 In this study, we found that cMet-low HCC cells showed primary resistance to cMet inhibitors, and the combination of cabozantinib and mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exhibited a synergistic inhibitory effect on the in vitro cell proliferation and in vivo tumor growth of these cells. Sirolimus 182-191 mechanistic target of rapamycin kinase Homo sapiens 134-163 34735882-1 2021 Abnormal activation of the mechanistic target of rapamycin (mTOR) signaling is commonly observed in many cancers and attracts extensive attention as an oncology drug discovery target, which is encouraged by the success of rapamycin and its analogs (rapalogs) in treatment of mTORC1-hyperactive cancers in both pre-clinic models and clinical trials. Sirolimus 222-231 mechanistic target of rapamycin kinase Homo sapiens 27-58 34735882-1 2021 Abnormal activation of the mechanistic target of rapamycin (mTOR) signaling is commonly observed in many cancers and attracts extensive attention as an oncology drug discovery target, which is encouraged by the success of rapamycin and its analogs (rapalogs) in treatment of mTORC1-hyperactive cancers in both pre-clinic models and clinical trials. Sirolimus 222-231 mechanistic target of rapamycin kinase Homo sapiens 60-64 34669157-3 2021 In this study, we found that cMet-low HCC cells showed primary resistance to cMet inhibitors, and the combination of cabozantinib and mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exhibited a synergistic inhibitory effect on the in vitro cell proliferation and in vivo tumor growth of these cells. Sirolimus 182-191 mechanistic target of rapamycin kinase Homo sapiens 165-169 34669157-4 2021 Mechanically, the combination of rapamycin with cabozantinib resulted in the remarkable inhibition of AKT, extracellular signal-regulated protein kinases, mTOR, and common downstream signal molecules of receptor tyrosine kinases; decreased cyclin D1 expression; and induced cell cycle arrest. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 155-159 34543777-12 2021 Treatment of rapamycin and let-7i-5p inhibitor reversed the effects of downregulated DICER in cell viability, ratio of LC3-II/LC3-I, autophagosomes, cell apoptosis rate and the phosphorylation levels of PI3K/AKT/mTOR in A549/DDP cells. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 212-216 34321280-1 2021 PURPOSE: To evaluate the safety and tolerability in phase 1 first-in-human combination therapy with pexidartinib, an inhibitor of colony-stimulating factor-1 receptor, and sirolimus, an mTOR inhibitor, to target tumor associated macrophage (TAM) polarization in soft tissue sarcomas (STSs). Sirolimus 172-181 mechanistic target of rapamycin kinase Homo sapiens 186-190 34679726-10 2021 The mTOR inhibitor rapamycin produced a similar reduction in SGK1 mRNA and protein levels as well as phosphorylation. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 34635641-6 2021 Mechanistic studies have shown that MYH9 regulates stem cell-like features of LCCs by regulating the mTOR signaling pathway, which was supported by sphere formation experiments after LCCs were treated with inhibitors Rapamycin and CHIR-99021. Sirolimus 217-226 mechanistic target of rapamycin kinase Homo sapiens 101-105 34790050-13 2021 Rapamycin, an inhibitor of mTOR, remarkably abolished UBE2O-induced mTOR phosphorylation and HCC cell proliferation and mobility. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 34790050-13 2021 Rapamycin, an inhibitor of mTOR, remarkably abolished UBE2O-induced mTOR phosphorylation and HCC cell proliferation and mobility. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 68-72 34712915-0 2021 Rapamycin recruits SIRT2 for FKBP12 deacetylation during mTOR activity modulation in innate immunity. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 57-61 34475980-0 2021 Rapamycin suppresses the PI3K/AKT/mTOR signaling pathway by targeting SIRT1 in esophageal cancer. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 34-38 34475980-10 2021 In addition, SIRT1 transfection rescued the decreased level of phosphorylated (p)-PI3K, p-AKT and p-mTOR induced by rapamycin treatment. Sirolimus 116-125 mechanistic target of rapamycin kinase Homo sapiens 100-104 34475980-11 2021 Taken together, the present results suggested that rapamycin suppressed the cell viability, migration, invasion and PI3K/AKT/mTOR signaling pathway in EC by negatively regulating SIRT1. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 125-129 34168367-3 2021 These "bi-steric inhibitors" comprise a rapamycin-like core moiety covalently linked to an mTOR active-site inhibitor. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 91-95 34399087-5 2021 Treatment of JEG-3 cells with GRalpha siRNA, LY294002, XO/HX or rapamycin inhibited phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, glycogen synthase kinase 3 and mammalian target of rapamycin (mTOR) and induced the phosphorylation of AMP-activated protein kinase (AMPK) and tuberous sclerosis complex 2. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 177-206 34399087-5 2021 Treatment of JEG-3 cells with GRalpha siRNA, LY294002, XO/HX or rapamycin inhibited phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, glycogen synthase kinase 3 and mammalian target of rapamycin (mTOR) and induced the phosphorylation of AMP-activated protein kinase (AMPK) and tuberous sclerosis complex 2. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 208-212 34119651-0 2021 Review: Schistosoma mansoni phosphatidylinositol 3 kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 102-106 34351835-4 2021 Drugs targeting mTOR and AMPK, such as sirolimus, rapamycin, and metformin, have shown some efficacy and tolerability in clinical trials on patients with SLE, but have not led to breakthroughs. Sirolimus 39-48 mechanistic target of rapamycin kinase Homo sapiens 16-20 34351835-4 2021 Drugs targeting mTOR and AMPK, such as sirolimus, rapamycin, and metformin, have shown some efficacy and tolerability in clinical trials on patients with SLE, but have not led to breakthroughs. Sirolimus 50-59 mechanistic target of rapamycin kinase Homo sapiens 16-20 34627459-2 2021 Sirolimus, as an immunosuppressant against of mTOR, induces immune tolerance by adjusting Treg cells, which has application prospect in the treatment of refractory autoimmune cytopenia. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 46-50 34712915-3 2021 The FKBP12-mTOR association can be strengthened by the immunosuppressant rapamycin, but the underlying mechanism remains elusive. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 11-15 34712915-10 2021 In contrast, rapamycin strengthening FKBP12-mTOR association blocks mTOR antiviral activity by recruiting SIRT2 to deacetylate FKBP12. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 44-48 34632383-2 2021 The main cellular activity of the mechanistic target of rapamycin cascade funnels through mechanistic target of rapamycin complex 1, which is inhibited by rapamycin, a macrolide compound produced by the bacterium Streptomyces hygroscopicus. Sirolimus 112-121 mechanistic target of rapamycin kinase Homo sapiens 34-65 34632383-2 2021 The main cellular activity of the mechanistic target of rapamycin cascade funnels through mechanistic target of rapamycin complex 1, which is inhibited by rapamycin, a macrolide compound produced by the bacterium Streptomyces hygroscopicus. Sirolimus 155-164 mechanistic target of rapamycin kinase Homo sapiens 34-65 34712915-10 2021 In contrast, rapamycin strengthening FKBP12-mTOR association blocks mTOR antiviral activity by recruiting SIRT2 to deacetylate FKBP12. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 68-72 34572126-6 2021 Rapamycin preconditioning resulted in activated autophagy and improved survival of ADSCs achieved by increased autophagosomes, upregulated autophagy-specific LC3-II gene, decreased protein degradation/ubiquitination by downregulated p62 gene, downregulated mTOR gene, and finally, upregulated antiapoptotic BCL-2 gene. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 257-261 34554926-7 2021 In addition, the mechanism of action of miR-19b-3p was clarified using the PTEN inhibitor (VO-Ohpic triphosphate) or the mTOR inhibitor (Rapamycin) on the basis of IL-1beta intervention and miR-19b-3p mimics transfection. Sirolimus 137-146 mechanistic target of rapamycin kinase Homo sapiens 121-125 34543857-9 2021 Consistently, SKO cells were more responsive to mTOR inhibition by rapamycin and presented impairment of the feedback activation loop in Akt. Sirolimus 67-76 mechanistic target of rapamycin kinase Homo sapiens 48-52 34531361-2 2021 For this reason, the mammalian target of rapamycin inhibitors (mTORi) such as sirolimus (SRL) and everolimus (EVE) has been preferred more frequently, as they are associated with fewer complications and longer graft function. Sirolimus 78-87 mechanistic target of rapamycin kinase Homo sapiens 21-50 34089901-5 2021 The activation of mammalian target of rapamycin (mTOR) signaling is one of the core and detrimental mechanisms related to aging; rapamycin can reduce the rate of aging, improve age-related diseases by inhibiting the mTOR pathway, and prolong lifespan and healthspan effectively. Sirolimus 129-138 mechanistic target of rapamycin kinase Homo sapiens 18-47 34114360-2 2021 First-generation mTOR inhibitors include rapamycin and its analogues (rapalogs) which act as allosteric inhibitors of TORC1. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 17-21 34493557-3 2021 Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, is frequently used as a second-line maintenance immunosuppressive agent in solid organ transplant recipients. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 13-42 34493557-3 2021 Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, is frequently used as a second-line maintenance immunosuppressive agent in solid organ transplant recipients. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 44-48 34089901-5 2021 The activation of mammalian target of rapamycin (mTOR) signaling is one of the core and detrimental mechanisms related to aging; rapamycin can reduce the rate of aging, improve age-related diseases by inhibiting the mTOR pathway, and prolong lifespan and healthspan effectively. Sirolimus 129-138 mechanistic target of rapamycin kinase Homo sapiens 49-53 34089901-5 2021 The activation of mammalian target of rapamycin (mTOR) signaling is one of the core and detrimental mechanisms related to aging; rapamycin can reduce the rate of aging, improve age-related diseases by inhibiting the mTOR pathway, and prolong lifespan and healthspan effectively. Sirolimus 129-138 mechanistic target of rapamycin kinase Homo sapiens 216-220 34405459-2 2021 The aim of this study was to compare the protracted effects of adolescent versus late-adolescent chronic exposure to THC on short-term memory and plasticity, and to examine whether rapamycin, a blocker of the mammalian target of rapamycin (mTOR) pathway, can restore THC-induced deficits in memory and plasticity. Sirolimus 181-190 mechanistic target of rapamycin kinase Homo sapiens 209-238 34242625-7 2021 Furthermore, we inhibited HIF1-alpha with PX-478 and inactivated mTOR with Rapamycin before the silence of PTEN in H/R model. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 65-69 34405459-2 2021 The aim of this study was to compare the protracted effects of adolescent versus late-adolescent chronic exposure to THC on short-term memory and plasticity, and to examine whether rapamycin, a blocker of the mammalian target of rapamycin (mTOR) pathway, can restore THC-induced deficits in memory and plasticity. Sirolimus 181-190 mechanistic target of rapamycin kinase Homo sapiens 240-244 34331013-4 2021 The mTOR inhibitors, sirolimus, everolimus, and temsirolimus, were the most active single agents tested, potently induced tumor-suppressive autophagy, but not apoptosis. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 4-8 34214676-10 2021 Moreover, PA interacts with the rapamycin binding domain of mTOR, demonstrated by the molecular dynamic (MD) simulation and binding free energy calculations. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 60-64 34304249-6 2021 The mTOR inhibitors, rapamycin and NVP-BEZ235, induced cell cycle arrest and apoptosis in CR cell lines. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 4-8 34102263-3 2021 Additionally, the therapeutic effects of rapamycin, an allosteric inhibitor of mammalian target of rapamycin (mTOR), which negatively regulates autophagy, on the sensory disturbance are not fully investigated. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 79-108 34512728-12 2021 We observed that the target proteins of the FDA-approved drug rapamycin (a known inhibitor of mTOR) were conserved across all four species. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 94-98 34445344-6 2021 Rapamycin, as an mTOR inhibitor, blocked T3-induced autophagic suppression and UCP1 upregulation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 17-21 34445268-2 2021 Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has a proven efficacy in patients with LAM. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 13-42 34445268-2 2021 Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has a proven efficacy in patients with LAM. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 44-48 34445268-7 2021 Sirolimus showed efficacy in patients with LAM, who exhibited a reduced expression of mTOR and p-cofilin as well as reduced interstitial septal thickness. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 86-90 34445268-8 2021 In addition, sirolimus suppresses mTOR and p-cofilin, thus suppressing the migration and proliferation of LAM cells isolated from the patient"s lung tissue. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 34-38 34361836-1 2021 Zotarolimus is a semi-synthetic derivative of rapamycin and an inhibitor of mammalian target of rapamycin (mTOR) signaling. Sirolimus 46-55 mechanistic target of rapamycin kinase Homo sapiens 107-111 34522186-11 2021 Furthermore, inhibition of the AKT/mTOR signaling by MK2206 or rapamycin significantly attenuated PRMT4-mediated malignant phenotypes. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 35-39 34540765-5 2021 Targeted therapies with PI3Kdelta-Akt-mTOR pathway pharmacologic inhibitors (i.e., Rapamycin, Theophylline, PI3K inhibitors) represent a good therapeutic strategy. Sirolimus 83-92 mechanistic target of rapamycin kinase Homo sapiens 38-42 34527488-5 2021 Use of sirolimus in a patient with renal transplant recipient helped in preventing intensification of the severity in COVID-19 attributing to its inhibiting effect on mammalian target of rapamycin (mTOR) which he was using post his renal transplant, therefore, proving to be a blessing in disguise. Sirolimus 7-16 mechanistic target of rapamycin kinase Homo sapiens 167-196 34527488-5 2021 Use of sirolimus in a patient with renal transplant recipient helped in preventing intensification of the severity in COVID-19 attributing to its inhibiting effect on mammalian target of rapamycin (mTOR) which he was using post his renal transplant, therefore, proving to be a blessing in disguise. Sirolimus 7-16 mechanistic target of rapamycin kinase Homo sapiens 198-202 34368895-2 2022 Our previous study showed that inhibition of MTOR with rapamycin treatment suppressed human endothelial cell tube formation, concomitant with the down-regulation of miR-107. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 45-49 34452154-1 2021 The phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (Akt)/mammalian target of the rapamycin (mTOR)-signaling pathway has been suggested to have connections with the malignant transformation, growth, proliferation, and metastasis of various cancers and solid tumors. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 106-110 34102263-3 2021 Additionally, the therapeutic effects of rapamycin, an allosteric inhibitor of mammalian target of rapamycin (mTOR), which negatively regulates autophagy, on the sensory disturbance are not fully investigated. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 110-114 34394184-8 2021 Then, the combined application of overexpressed PDK1 and rapamycin verified that PDK1 could regulate the expression of PD-L1 in NSCLC cells through the mTOR signaling pathway. Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 152-156 34331820-1 2022 The mammalian target of rapamycin inhibitor (mTOR-I) Rapamycin, a drug widely used in kidney transplantation, exerts important anti-cancer effects, particularly in Kaposi"s Sarcoma (KS), through several biological interactions. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 4-33 34331820-7 2022 In conclusion, our in vitro data demonstrated, for the first time, that in Kaposi"s sarcoma, autophagy triggered by Rapamycin through p75NTR represented a major mechanism by which mTOR inhibitors may induce tumor regression. Sirolimus 116-125 mechanistic target of rapamycin kinase Homo sapiens 180-184 34590575-5 2021 Fatty acids and glucose metabolites are involved in regulation of immune response mainly via free fatty acid receptors and AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway. Sirolimus 172-181 mechanistic target of rapamycin kinase Homo sapiens 188-192 34238334-11 2021 Currently, there are no systemic agents that have regulatory approval for these disorders, but the mTOR inhibitor sirolimus has been used for several years in clinical trials and off label to address symptoms. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 99-103 34594200-3 2021 Variable therapeutic modalities were used in the management of BRBNS; sirolimus (SRL), a mammalian target of rapamycin (mTOR) inhibitor, is found to be a promising therapy for vascular anomalies. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 89-118 34594200-3 2021 Variable therapeutic modalities were used in the management of BRBNS; sirolimus (SRL), a mammalian target of rapamycin (mTOR) inhibitor, is found to be a promising therapy for vascular anomalies. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 120-124 34594200-3 2021 Variable therapeutic modalities were used in the management of BRBNS; sirolimus (SRL), a mammalian target of rapamycin (mTOR) inhibitor, is found to be a promising therapy for vascular anomalies. Sirolimus 81-84 mechanistic target of rapamycin kinase Homo sapiens 89-118 34594200-3 2021 Variable therapeutic modalities were used in the management of BRBNS; sirolimus (SRL), a mammalian target of rapamycin (mTOR) inhibitor, is found to be a promising therapy for vascular anomalies. Sirolimus 81-84 mechanistic target of rapamycin kinase Homo sapiens 120-124 34421360-9 2021 Mechanistically, rapamycin in combination with trametinib resulted in a greater decrease of phosphorylation of AKT, ERK, mTOR and 4EBP1. Sirolimus 17-26 mechanistic target of rapamycin kinase Homo sapiens 121-125 34281475-1 2021 BACKGROUND: Sirolimus constitutes a safe and effective treatment for cardiac manifestations of tuberous sclerosis complex (TSC) in children but only four cases describing prenatal treatment of rhabdomyomas with mTOR inhibitors have been published. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 211-215 34235896-8 2021 Intravitreal administration of rapamycin, a negative regulator of mTOR, inhibits the mTOR pathway in rd1 photoreceptors. Sirolimus 31-40 mechanistic target of rapamycin kinase Homo sapiens 66-70 34235896-8 2021 Intravitreal administration of rapamycin, a negative regulator of mTOR, inhibits the mTOR pathway in rd1 photoreceptors. Sirolimus 31-40 mechanistic target of rapamycin kinase Homo sapiens 85-89 34282122-6 2021 Moreover, both AMP-activated protein kinase (AMPK) agonist metformin and two mammalian targets of rapamycin (mTOR) inhibitors (INK128 and rapamycin) inhibited the percentage of M-MDSCs in lupus mice as well as in the TLR7- and IFN-alpha-induced bone marrow (BM) differentiation into MDSCs in vitro. Sirolimus 98-107 mechanistic target of rapamycin kinase Homo sapiens 109-113 34282122-6 2021 Moreover, both AMP-activated protein kinase (AMPK) agonist metformin and two mammalian targets of rapamycin (mTOR) inhibitors (INK128 and rapamycin) inhibited the percentage of M-MDSCs in lupus mice as well as in the TLR7- and IFN-alpha-induced bone marrow (BM) differentiation into MDSCs in vitro. Sirolimus 138-147 mechanistic target of rapamycin kinase Homo sapiens 109-113 34326770-1 2021 Background: Mammalian target of rapamycin (mTOR) inhibitors, such as everolimus and sirolimus, may be efficacious in preserving renal function in liver transplantation (LT) recipients while preventing hepatocellular carcinoma (HCC) recurrence. Sirolimus 84-93 mechanistic target of rapamycin kinase Homo sapiens 12-41 34326770-1 2021 Background: Mammalian target of rapamycin (mTOR) inhibitors, such as everolimus and sirolimus, may be efficacious in preserving renal function in liver transplantation (LT) recipients while preventing hepatocellular carcinoma (HCC) recurrence. Sirolimus 84-93 mechanistic target of rapamycin kinase Homo sapiens 43-47 34356626-5 2021 Interestingly, circadian pathways hold an intricate relationship with autophagy, the mechanistic target of rapamycin (mTOR), the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), mammalian forkhead transcription factors (FoxOs), and the trophic factor erythropoietin. Sirolimus 107-116 mechanistic target of rapamycin kinase Homo sapiens 118-122 34135202-5 2021 Based on these results we decided to test a novel treatment using sirolimus, an mTOR inhibitor, for epileptic seizures in patients with FCD type II. Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 80-84 34401617-2 2021 Sirolimus is a mechanistic target of rapamycin inhibitor used as an immunosuppressive drug. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 15-46 34276381-9 2021 Rapamycin, an inhibitor of mTOR, prevented oligodendrocyte growth differentiation and myelination. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 34215308-7 2021 Beyond rapamycin; an mTOR inhibitor, there are rapalogs having greater tolerability and micro delivery modes, that hold promise in arresting these age dependent conditions. Sirolimus 7-16 mechanistic target of rapamycin kinase Homo sapiens 21-25 34209274-4 2021 The mammalian target of the Rapamycin (mTOR) signaling pathway that acts via two distinct multiprotein complexes, mTORC1 and mTORC2, can affect oxidative stress. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 39-43 34276381-12 2021 The finding that these effects are reduced when OPCs are exposed to rapamycin suggests an involvement of mTOR signaling in PEALut effects. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 105-109 34226528-6 2021 Inhibition of mammalian target of rapamycin (mTOR) by rapamycin preserved tight junction proteins and attenuated BBB leakage and neuronal apoptosis after HI in the endothelial-specific IRS-1 transgenic pups. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 14-43 34226528-6 2021 Inhibition of mammalian target of rapamycin (mTOR) by rapamycin preserved tight junction proteins and attenuated BBB leakage and neuronal apoptosis after HI in the endothelial-specific IRS-1 transgenic pups. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 45-49 34209599-5 2021 Metabolic dysfunction, upregulation of the mammalian target of the rapamycin (mTOR) pathway, the gut microbiome, 3-hydroxyisobutyrate, inflammation, and the collusion of G-protein coupled receptors (GPCRs) are among the indicators and causes of metabolic disorders generating from amino acids that contribute to IR and the onset of type 2 diabetes mellitus (T2DM). Sirolimus 67-76 mechanistic target of rapamycin kinase Homo sapiens 78-82 34142125-9 2021 Incubation of human pluripotent stem cell-derived cardiomyocytes with elevated concentration of BCAAs induced similar calcium dysregulation and pro-arrhythmic events which were prevented by rapamycin, demonstrating the crucial involvement of mTOR pathway activation. Sirolimus 190-199 mechanistic target of rapamycin kinase Homo sapiens 242-246 34180556-9 2022 Moreover, rapamycin, a mTOR inhibitor, could enhance the cytotoxicity effect in xanthatin treated HT-29 cells. Sirolimus 10-19 mechanistic target of rapamycin kinase Homo sapiens 23-27 34249417-1 2021 The phosphatidylinositol 3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) signaling pathways are critical for normal human physiology, and any alteration in their regulation leads to several human cancers. Sirolimus 78-87 mechanistic target of rapamycin kinase Homo sapiens 89-93 34082911-2 2021 Sirolimus, a mammalian target of rapamycin inhibitor, has demonstrated promise as a primary medical therapy for PVS, but the impact on patient survival is unknown. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 13-42 34082911-3 2021 OBJECTIVES: The authors sought to investigate whether mTOR inhibition with sirolimus as a primary medical therapy would improve outcomes in high-risk infants and children with PVS. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 54-58 34104708-6 2021 IF inhibits the mTOR pathway which is similar to the effects of Rapamycin in some animal models. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 16-20 34103076-3 2021 Sirolimus, which is an inhibitor of mammalian target of rapamycin, has been shown to have promising potential in the treatment of complicated vascular anomalies. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 36-65 34079249-8 2021 Furthermore, exosomal anti-let-7i-5p promoted the activation the tuberous sclerosis complex subunit 1/mammalian target of rapamycin (TSC1/mTOR) signaling pathway in vivo and in vitro. Sirolimus 122-131 mechanistic target of rapamycin kinase Homo sapiens 138-142 33269749-11 2021 Both LY294002 (20 muM) and rapamycin (500 nM), which are inhibitors of the PI3K/Akt/mTOR pathway, significantly attenuated the inhibition of autophagy and apoptosis caused by apelin-13. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 84-88 34258421-4 2021 The concentrations of most serum AA and the AA transporters related gene expressions were highest in 7-d-old piglets (P < 0.05), whereas the phosphorylation status of the mammalian target of the rapamycin (mTOR) signaling pathway in the small intestine increased in piglets from 1 to 21 d old (P < 0.05). Sirolimus 195-204 mechanistic target of rapamycin kinase Homo sapiens 206-210 34295558-2 2021 Methods: We retrospectively analyzed the clinical data of 46 patients who underwent liver transplantation for HCC and performed next generation sequencing to analyze the relationship between the efficacy of sirolimus after liver transplantation for HCC and mutations in mTOR pathway-related genes, especially tuberous sclerosis complex (TSC) mutations. Sirolimus 207-216 mechanistic target of rapamycin kinase Homo sapiens 270-274 34295558-7 2021 Of the 35 patients using sirolimus, those with mTOR-related mutations had significantly better survival rates than patients without mTOR-related mutations (P=0.016). Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 47-51 34295558-7 2021 Of the 35 patients using sirolimus, those with mTOR-related mutations had significantly better survival rates than patients without mTOR-related mutations (P=0.016). Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 132-136 34295558-9 2021 Patients with mTOR-related gene mutations, especially TSC mutations, can gain significant benefits from the use of mTOR inhibitors such as sirolimus. Sirolimus 139-148 mechanistic target of rapamycin kinase Homo sapiens 14-18 34295558-9 2021 Patients with mTOR-related gene mutations, especially TSC mutations, can gain significant benefits from the use of mTOR inhibitors such as sirolimus. Sirolimus 139-148 mechanistic target of rapamycin kinase Homo sapiens 115-119 34247157-11 2021 Functionally, rapamycin, but not Gleevec, significantly enhanced the expression of endothelial differentiation marker proteins, while attenuating the expression of mammalian target of rapamycin signaling-related proteins. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 164-193 34065350-5 2021 Administration of the mTOR inhibitor rapamycin rescues mitochondrial alterations. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 22-26 34915755-7 2021 Moreover, Cisplatin-induced activation of mammalian target of rapamycin mTOR and inactivation of AMPK/PI3K/Akt signal pathway, and was coupled with induction of p53 activity and the executioner caspase3 to induce apoptotic renal cell death. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 72-76 34073791-2 2021 Neuroprotection and recovery after SCI can be partially achieved by rapamycin (RAPA) treatment, an inhibitor of mTORC1, complex 1 of the mammalian target of rapamycin (mTOR) pathway. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 137-166 34073791-2 2021 Neuroprotection and recovery after SCI can be partially achieved by rapamycin (RAPA) treatment, an inhibitor of mTORC1, complex 1 of the mammalian target of rapamycin (mTOR) pathway. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 168-172 34073791-2 2021 Neuroprotection and recovery after SCI can be partially achieved by rapamycin (RAPA) treatment, an inhibitor of mTORC1, complex 1 of the mammalian target of rapamycin (mTOR) pathway. Sirolimus 79-83 mechanistic target of rapamycin kinase Homo sapiens 137-166 34073791-2 2021 Neuroprotection and recovery after SCI can be partially achieved by rapamycin (RAPA) treatment, an inhibitor of mTORC1, complex 1 of the mammalian target of rapamycin (mTOR) pathway. Sirolimus 79-83 mechanistic target of rapamycin kinase Homo sapiens 168-172 34123648-2 2021 Recent reports have suggested that mTOR inhibitor sirolimus and related drugs show some benefit in non-tuberous sclerosis complex PEComas. Sirolimus 50-59 mechanistic target of rapamycin kinase Homo sapiens 35-39 34703427-1 2021 We present a rare case of KRAS keratinocytic epidermal nevus syndrome with lymphatic malformation, responsive to treatment with sirolimus, an mTOR inhibitor. Sirolimus 128-137 mechanistic target of rapamycin kinase Homo sapiens 142-146 34084203-4 2021 Determining effective environmental factors such as stress conditions on the expression of PD1 and PD-L1 genes can provide an immunotherapeutic strategy to control PD1 signaling in the patients Mammalian target of rapamycin signaling is a stress-responsive pathway in the cells that can be blocked by rapamycin. Sirolimus 301-310 mechanistic target of rapamycin kinase Homo sapiens 194-223 34187243-5 2021 After repeated recurrence, the patient was treated with mTOR inhibitor sirolimus, which had a safety mechanism and specifically rebalance the DNT/Treg axis. Sirolimus 71-80 mechanistic target of rapamycin kinase Homo sapiens 56-60 34522717-10 2021 Here, we showed the coexistence of immunodeficiency and SLE phenotype in APDS1, and the inhibition of rapamycin in activated Akt-mTOR signaling pathway. Sirolimus 102-111 mechanistic target of rapamycin kinase Homo sapiens 129-133 34476091-2 2021 The mammalian target of rapamycin inhibitor sirolimus (SRL) has immunosuppressive and antitumour activities but knowledge about its use in recipients with cancer is limited. Sirolimus 44-53 mechanistic target of rapamycin kinase Homo sapiens 4-33 34476091-2 2021 The mammalian target of rapamycin inhibitor sirolimus (SRL) has immunosuppressive and antitumour activities but knowledge about its use in recipients with cancer is limited. Sirolimus 55-58 mechanistic target of rapamycin kinase Homo sapiens 4-33 35487271-8 2022 Application of rapamycin, the mTOR inhibitor, significantly reduced the upregulation of the proliferation, migration, and invasion abilities of lung adenocarcinoma cells transfected with Rab22a. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 30-34 35489420-10 2022 MiR-199a-3p directly targeted and repressed mTOR, and its suppression effect on ICAM-1 and VCAM-1 was abolished by mTOR inhibitor rapamycin, and rescued by mTOR activator MHY1485. Sirolimus 130-139 mechanistic target of rapamycin kinase Homo sapiens 44-48 35192892-6 2022 However, these effects were markedly reversed by MARKs inhibitor 39621, or MARK2/4 deletion, mTOR inhibitor rapamycin, or AMPK activator AICAR. Sirolimus 108-117 mechanistic target of rapamycin kinase Homo sapiens 93-97 35428493-10 2022 WB results showed that LC3-II/I expression was significantly elevated in KHE primary cells treated with rapamycin, while the level of p-mTOR, p-S6K1, and p-4E-BP1 expression was reduced. Sirolimus 104-113 mechanistic target of rapamycin kinase Homo sapiens 136-140 35428493-12 2022 CONCLUSIONS: Rapamycin inhibited KHE primary cell proliferation, induced apoptosis and autophagy, and blocked the mTOR signaling pathway. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 114-118 35605444-3 2022 The patients were treated with mTOR inhibitors (rapamycin). Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 31-35 35489420-10 2022 MiR-199a-3p directly targeted and repressed mTOR, and its suppression effect on ICAM-1 and VCAM-1 was abolished by mTOR inhibitor rapamycin, and rescued by mTOR activator MHY1485. Sirolimus 130-139 mechanistic target of rapamycin kinase Homo sapiens 115-119 35176419-8 2022 Currently, the only clinically available p70S6K inhibitors are rapamycin analogs (rapalogs) which target mTOR. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 105-109 35521831-4 2022 One such drug, rapamycin, is currently under study for this purpose, given its immunosuppressant effects that are mediated by its inhibition of the mechanistic target of rapamycin (mTOR), a master regulator of cell growth. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 148-179 35521831-4 2022 One such drug, rapamycin, is currently under study for this purpose, given its immunosuppressant effects that are mediated by its inhibition of the mechanistic target of rapamycin (mTOR), a master regulator of cell growth. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 181-185 35521831-5 2022 Consistent with this premise, acute rapamycin administration in young healthy humans blocks or attenuates mTOR and its downstream effectors, leading to the inhibition of muscle protein synthesis (MPS). Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 106-110 35585420-9 2022 Notably, their expressions were decreased when the mTOR pathway was inhibited by rapamycin. Sirolimus 81-90 mechanistic target of rapamycin kinase Homo sapiens 51-55 35363301-1 2022 PURPOSE: To report efficacy and safety of samotolisib (LY3023414; phosphoinositide 3- kinase/mechanistic target of rapamycin (PI3K/mTOR) dual kinase and DNA-dependent protein kinase (DNA-PK) inhibitor) plus enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) following cancer progression on abiraterone. Sirolimus 115-124 mechanistic target of rapamycin kinase Homo sapiens 131-135 35107743-12 2022 Studies on other respiratory viruses suggest that the therapeutic inhibitors of the mTOR pathway, especially rapamycin, can be a potential approach to anti-SARS-CoV-2 therapy. Sirolimus 109-118 mechanistic target of rapamycin kinase Homo sapiens 84-88 35488725-4 2022 The mTOR inhibitor sirolimus, which preferentially inhibits mTORC1, has led to sustained remission in a small cohort of anti-IL-6-refractory iMCD patients with thrombocytopenia, anasarca, fever, renal dysfunction and organomegaly (iMCD-TAFRO). Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 35286973-8 2022 The levels of phosphorylated mTOR and ribosomal protein S6 kinase 1 (p70S6K) were increased after GLUT1 inhibition and decreased by an mTOR inhibitor (rapamycin, Rapa) during the odontogenic induction of hDPSCs. Sirolimus 151-160 mechanistic target of rapamycin kinase Homo sapiens 29-33 35286973-8 2022 The levels of phosphorylated mTOR and ribosomal protein S6 kinase 1 (p70S6K) were increased after GLUT1 inhibition and decreased by an mTOR inhibitor (rapamycin, Rapa) during the odontogenic induction of hDPSCs. Sirolimus 151-160 mechanistic target of rapamycin kinase Homo sapiens 135-139 35588700-8 2022 Among the mTOR inhibitors, everolimus and sirolimus showed the best results. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 10-14 35573101-7 2022 Sirolimus could effectively block the upstream and downstream factors of mammalian target of rapamycin signaling pathways to achieve the antiangiogenic effect. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 73-102 35526176-4 2022 METHODS: A systematic search of the literature regarding studies on sirolimus treatment of children with lymphatic malformations of the head and neck was performed in PubMed, Embase, and Google Scholar up to July 2021 with the search terms "lymphatic malformation", "lymphangioma", "cystic hygroma", "low-flow malformation", "sirolimus", "rapamycin", "mTOR inhibitor" and "children". Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 352-356 35506423-3 2022 Everolimus is a mechanistic/mammalian target of rapamycin (mTOR) inhibitor used to prevent tumor growth by inhibiting the PI3K signaling pathway. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 59-63 35218870-7 2022 The use of rapamycin to prolong life in different animal models may be attributable to the multiple roles played by mTOR signaling in various processes involved in ageing, protein translation, autophagy, stem cell pool turnover, inflammation, and cellular senescence. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 116-120 35380294-14 2022 Despite Diaph3 expression not correlating with survival and tumor size in GBM, there is an accumulating body of evidence that Diaph3 correlates with mTOR activity and can thus be used as a predictor for response to rapamycin and taxanes, clinical studies of which have shown promising, if mixed results in GBM. Sirolimus 215-224 mechanistic target of rapamycin kinase Homo sapiens 149-153 35299066-2 2022 Besides providing nitrogen substrates and carbon framework for energy homeostasis and transamination, BCAA also function as signaling molecules in the regulation of glucose, lipid, and protein synthesis via protein kinase B and as a mechanistic target of the rapamycin (AKT-mTOR) signaling pathway that is important for muscle accretion. Sirolimus 259-268 mechanistic target of rapamycin kinase Homo sapiens 274-278 35571122-9 2022 Both mycophenolic acid and rapamycin inhibited inflammatory and fibrotic processes induced by TGF-beta1 or IL-6 by downregulating mTOR and ERK phosphorylation. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 130-134 35405122-7 2022 RN-1747 and rapamycin molecules were successfully loaded in sHA-oleylamide, previously prepared at 12 mg/mL in PBS; both formulations were stable, sterile and confirmed in vitro to have mTOR inhibition by rapamycin and TRPV4 activation activity by RN-1747. Sirolimus 205-214 mechanistic target of rapamycin kinase Homo sapiens 186-190 35472723-6 2022 These alterations, which mirror diabetes-associated human beta-cell dysfunction, are partially reversed by acute mTOR inhibition with rapamycin. Sirolimus 134-143 mechanistic target of rapamycin kinase Homo sapiens 113-117 35436937-1 2022 BACKGROUND: Increasing evidence has shown that the mammalian target of rapamycin (mTOR) pathway plays a critical role in oocyte meiosis and embryonic development, however, previous studies reporting the effects of rapamycin on oocyte IVM showed different or even opposite results, and the specific mechanisms were not clear. Sirolimus 214-223 mechanistic target of rapamycin kinase Homo sapiens 51-80 35436937-1 2022 BACKGROUND: Increasing evidence has shown that the mammalian target of rapamycin (mTOR) pathway plays a critical role in oocyte meiosis and embryonic development, however, previous studies reporting the effects of rapamycin on oocyte IVM showed different or even opposite results, and the specific mechanisms were not clear. Sirolimus 214-223 mechanistic target of rapamycin kinase Homo sapiens 82-86 35444442-3 2022 Current research shows that rapamycin, an mTOR inhibitor, is probably a promising adjunctive therapy for PWS, which suggests that the mTOR signaling pathway may play an important role in its pathological process. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 42-46 35444442-3 2022 Current research shows that rapamycin, an mTOR inhibitor, is probably a promising adjunctive therapy for PWS, which suggests that the mTOR signaling pathway may play an important role in its pathological process. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 134-138 35456509-8 2022 The drugs with a mostly anti-correlated signature were: efavirenz, an anti-retroviral drug; tacrolimus, a calcineurin inhibitor; and sirolimus, an mTOR inhibitor. Sirolimus 133-142 mechanistic target of rapamycin kinase Homo sapiens 147-151 35143831-10 2022 Use of Sirolimus (mTOR inhibitor) was significantly associated with higher BCAA plasma levels, independent of age, sex, time after OLTx, MetS and other immunosuppressive medication (adjusted P=0.002). Sirolimus 7-16 mechanistic target of rapamycin kinase Homo sapiens 18-22 35406578-6 2022 Here, we aim to clarify the role of the hypoxia-responding mammalian target of the rapamycin (mTOR) pathway in esophageal CSCs. Sirolimus 83-92 mechanistic target of rapamycin kinase Homo sapiens 94-98 35391614-8 2022 Treatment with MAP kinase inhibitor U0126 prevented the change to a spindle-shaped morphology in NRASQ61R endothelial cells, whereas mTOR inhibitor rapamycin did not. Sirolimus 148-157 mechanistic target of rapamycin kinase Homo sapiens 133-137 35444553-2 2022 With its analogs (everolimus, ridaforolimus, and rapamycin), it forms a group of anticancer agents that block the activity of one of the two mammalian targets of rapamycin (mTOR) complexes, mTORC1. Sirolimus 49-58 mechanistic target of rapamycin kinase Homo sapiens 173-177 35444553-2 2022 With its analogs (everolimus, ridaforolimus, and rapamycin), it forms a group of anticancer agents that block the activity of one of the two mammalian targets of rapamycin (mTOR) complexes, mTORC1. Sirolimus 162-171 mechanistic target of rapamycin kinase Homo sapiens 173-177 35253967-1 2022 BACKGROUND AND PURPOSE: To provide further evidence for sirolimus, a mammalian target of rapamycin inhibitor, as a treatment strategy for patients with inclusion body myositis (IBM). Sirolimus 56-65 mechanistic target of rapamycin kinase Homo sapiens 69-98 35040506-0 2022 mTOR Inhibition with Sirolimus in Multiple System Atrophy: A Randomized, Double-Blind, Placebo-Controlled Futility Trial and 1-Year Biomarker Longitudinal Analysis. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 0-4 35183509-3 2022 We hypothesized that systemic induction of autophagy, via phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) inhibition, would be effective in preventing anal cancer development in human papillomavirus (HPV) mice (K14E6/E7) with established low-grade anal dysplasia. Sirolimus 104-113 mechanistic target of rapamycin kinase Homo sapiens 120-124 35040506-2 2022 Sirolimus (rapamycin) is an mTOR inhibitor that promotes alpha-synuclein autophagy and reduces its associated neurotoxicity in preclinical models. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 28-32 35040506-2 2022 Sirolimus (rapamycin) is an mTOR inhibitor that promotes alpha-synuclein autophagy and reduces its associated neurotoxicity in preclinical models. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 28-32 35153184-1 2022 OBJECTIVE: The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of the rapamycin (PI3K-AKT-mTOR) signaling pathway is an important regulator of cell proliferation, survival, and motility. Sirolimus 86-95 mechanistic target of rapamycin kinase Homo sapiens 106-110 35088890-1 2022 The phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathway is a therapeutic target for various types of human tumors, and dual PI3K/mTOR inhibitors demonstrate antitumor activities in both preclinical and clinical studies. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 70-74 35358003-5 2022 Rapamycin, a reversible inhibitor of growth, slows down mTOR-driven geroconversion. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 56-60 35316619-1 2022 The protein kinase mechanistic target of rapamycin (mTOR) functions as a central regulator of metabolism, integrating diverse nutritional and hormonal cues to control anabolic processes, organismal physiology, and even aging. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 52-56 35433677-8 2022 Our results showed patients in C2 NSCLC had the highest sensitivity to MK.2206 (AKT.inhibitor) and Rapamycin (mTOR inhibitor). Sirolimus 99-108 mechanistic target of rapamycin kinase Homo sapiens 110-114 35348612-2 2022 Multiple studies, sought to reveal the precise mechanism employed, commonly used autophagy inducers, such as rapamycin, which is a mammalian target of rapamycin (mTOR) inhibitor. Sirolimus 109-118 mechanistic target of rapamycin kinase Homo sapiens 131-160 35348612-2 2022 Multiple studies, sought to reveal the precise mechanism employed, commonly used autophagy inducers, such as rapamycin, which is a mammalian target of rapamycin (mTOR) inhibitor. Sirolimus 109-118 mechanistic target of rapamycin kinase Homo sapiens 162-166 35359607-8 2022 The previous inhibition of mTOR by rapamycin had a synergistic effect with SFs, reducing cell viability even more significantly than the untreated control. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 27-31 35337287-0 2022 Anti-angiogenic properties of rapamycin on human retinal pericytes in an in vitro model of neovascular AMD via inhibition of the mTOR pathway. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 129-133 35337287-4 2022 METHODS: The mTOR inhibitor rapamycin was used to treat human retinal pericytes (HRP) at doses ranging from 0.005 to 15 g/ml. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 13-17 35337287-12 2022 CONCLUSIONS: Rapamycin allows for an efficient modulation of aspects of angiogenesis in pericytes via mTOR-modulation in vitro. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 102-106 35372343-1 2022 Rapamycin, also known as sirolimus, an inhibitor of mammalian target of rapamycin (mTOR), is a regulatory kinase responsible for multiple signal transduction pathways. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 52-81 35372343-1 2022 Rapamycin, also known as sirolimus, an inhibitor of mammalian target of rapamycin (mTOR), is a regulatory kinase responsible for multiple signal transduction pathways. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 83-87 35372343-1 2022 Rapamycin, also known as sirolimus, an inhibitor of mammalian target of rapamycin (mTOR), is a regulatory kinase responsible for multiple signal transduction pathways. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 52-81 35372343-1 2022 Rapamycin, also known as sirolimus, an inhibitor of mammalian target of rapamycin (mTOR), is a regulatory kinase responsible for multiple signal transduction pathways. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 83-87 35330555-1 2022 Background: Rapamycin was shown to reduce transforming growth factor beta1 (TGF-beta1) expression, inhibit the Mammalian target of rapamycin function, and prevent TGF-beta1-induced pulmonary fibrosis. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 111-140 35255005-5 2022 Mechanistic dissection demonstrated that FOXH1-induced cell growth and cell migration/invasion relied on mTOR signaling because inhibition of mTOR signaling by rapamycin could attenuate FOXH1-mediated phenotypic alterations of HCC cells. Sirolimus 160-169 mechanistic target of rapamycin kinase Homo sapiens 105-109 35255005-5 2022 Mechanistic dissection demonstrated that FOXH1-induced cell growth and cell migration/invasion relied on mTOR signaling because inhibition of mTOR signaling by rapamycin could attenuate FOXH1-mediated phenotypic alterations of HCC cells. Sirolimus 160-169 mechanistic target of rapamycin kinase Homo sapiens 142-146 35235808-6 2022 Treatment with the mTOR inhibitor rapamycin decreases the growth of syngeneic KPC tumors with Galpha13 loss by promoting cell death. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 19-23 35246210-5 2022 Although mTOR inhibitors (rapamycin/everolimus) demonstrate great potential in TSC management, two major concerns hamper their generalized application. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 9-13 35402590-3 2022 Sirolimus, an inhibitor of the mammalian target of rapamycin (mTOR), has been reported to reduce viral replication and improve clinical outcomes in severe H1N1 infections when combined with oseltamivir. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 31-60 35402590-3 2022 Sirolimus, an inhibitor of the mammalian target of rapamycin (mTOR), has been reported to reduce viral replication and improve clinical outcomes in severe H1N1 infections when combined with oseltamivir. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 62-66 35184679-0 2022 Rapamycin ameliorates chronic intermittent hypoxia and sleep deprivation-induced renal damage via the mammalian target of rapamycin (mTOR)/NOD-like receptor protein 3 (NLRP3) signaling pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 102-131 35184679-0 2022 Rapamycin ameliorates chronic intermittent hypoxia and sleep deprivation-induced renal damage via the mammalian target of rapamycin (mTOR)/NOD-like receptor protein 3 (NLRP3) signaling pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 133-137 35184679-1 2022 Rapamycin inhibits the activation of NOD-like receptor protein 3 (NLRP3) by regulating the mammalian target of rapamycin (mTOR) to treat obstructive sleep apnea-related renal injury. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 91-120 35184679-1 2022 Rapamycin inhibits the activation of NOD-like receptor protein 3 (NLRP3) by regulating the mammalian target of rapamycin (mTOR) to treat obstructive sleep apnea-related renal injury. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 122-126 35059731-6 2022 For instance, short-term treatment with mammalian target of rapamycin inhibitors (such as everolimus and sirolimus) has been found to improve responses to influenza vaccination in adults, with benefits possibly persisting for a year following treatment. Sirolimus 105-114 mechanistic target of rapamycin kinase Homo sapiens 40-69 35282339-6 2022 Our group has also demonstrated that conversion from calcineurin inhibitor to the mammalian target of rapamycin (mTOR) inhibitor, sirolimus, as a primary immunosuppression was associated with a decreased risk of PTLD following HT. Sirolimus 130-139 mechanistic target of rapamycin kinase Homo sapiens 82-111 35251323-1 2022 It has been reported that the mammalian target of rapamycin (mTOR) pathway is involved in the pathogenesis of systemic lupus erythematosus (SLE), and increasing evidence has shown the effect of mTOR-targeted therapies with sirolimus in SLE. Sirolimus 223-232 mechanistic target of rapamycin kinase Homo sapiens 30-59 35251323-1 2022 It has been reported that the mammalian target of rapamycin (mTOR) pathway is involved in the pathogenesis of systemic lupus erythematosus (SLE), and increasing evidence has shown the effect of mTOR-targeted therapies with sirolimus in SLE. Sirolimus 223-232 mechanistic target of rapamycin kinase Homo sapiens 61-65 35251323-1 2022 It has been reported that the mammalian target of rapamycin (mTOR) pathway is involved in the pathogenesis of systemic lupus erythematosus (SLE), and increasing evidence has shown the effect of mTOR-targeted therapies with sirolimus in SLE. Sirolimus 223-232 mechanistic target of rapamycin kinase Homo sapiens 194-198 35251323-5 2022 Treatment with the mTOR inhibitor sirolimus was initiated in this patient. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 19-23 35149934-2 2022 Convincing evidence indicates that the mTOR inhibitor rapamycin could play a fundamental role in protection against podocyte injury. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 39-43 35149934-8 2022 We further found that nestin co-localized with p-mTOR in glomeruli, and the protective effect of rapamycin was reduced by nestin-siRNA in podocytes. Sirolimus 97-106 mechanistic target of rapamycin kinase Homo sapiens 49-53 35149934-10 2022 CONCLUSION: We demonstrated that rapamycin attenuated podocyte apoptosis via upregulation of nestin expression through the mTOR/P70S6K signaling pathway in an Ang II-induced podocyte injury. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 123-127 35251315-3 2022 Genetic alterations in the mammalian target for rapamycin (mTOR) pathway have been identified in NEN, providing a rationale for treatment with the mTOR-inhibitor everolimus. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 59-63 35282339-6 2022 Our group has also demonstrated that conversion from calcineurin inhibitor to the mammalian target of rapamycin (mTOR) inhibitor, sirolimus, as a primary immunosuppression was associated with a decreased risk of PTLD following HT. Sirolimus 130-139 mechanistic target of rapamycin kinase Homo sapiens 113-117 35007565-7 2022 Western blot was used to determine the down-regulation of rapamycin (mTOR) signaling and autophagy enhancement induced by ORFV. Sirolimus 58-67 mechanistic target of rapamycin kinase Homo sapiens 69-73 35051778-8 2022 Further analysis revealed that MEOX2 negatively modulated the phosphatidyl-inositol-3 kinase (PI3K)/AKT/mammalian target of the rapamycin (mTOR) and extracellular signal-regulated kinase (ERK1/2) pathways. Sirolimus 128-137 mechanistic target of rapamycin kinase Homo sapiens 139-143 35182368-1 2022 It has recently emerged that drugs such as the mTOR inhibitor rapamycin (Rapa) may play a key role in the treatment of airway inflammation associated with lung diseases, such as chronic obstructive pulmonary disease, asthma, and cystic fibrosis. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 47-51 35182368-1 2022 It has recently emerged that drugs such as the mTOR inhibitor rapamycin (Rapa) may play a key role in the treatment of airway inflammation associated with lung diseases, such as chronic obstructive pulmonary disease, asthma, and cystic fibrosis. Sirolimus 73-77 mechanistic target of rapamycin kinase Homo sapiens 47-51 35114332-3 2022 Naturally aged C57BL/6J mice were used to identify the role of autophagy in ARHL, and rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, was administered for 34 weeks to explore the potential therapeutic effect of rapamycin in ARHL. Sirolimus 86-95 mechanistic target of rapamycin kinase Homo sapiens 130-134 35040598-1 2022 OBJECTIVE: To determine whether sirolimus, a mechanistic target of rapamycin (mTOR) inhibitor, reduces epileptic seizures associated with focal cortical dysplasia (FCD) type II. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 45-76 35125022-0 2022 Efficacy of mTOR inhibitors (sirolimus) in isolated limb overgrowth: a systematic review. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 12-16 35040598-1 2022 OBJECTIVE: To determine whether sirolimus, a mechanistic target of rapamycin (mTOR) inhibitor, reduces epileptic seizures associated with focal cortical dysplasia (FCD) type II. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 78-82 35143341-7 2022 Furthermore, hyperactivation of mTOR signaling was relieved by rapamycin. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 32-36 35085453-4 2022 Rapamycin, a mechanistic target of rapamycin (mTOR) inhibitor, was added during rabbit embryonic fibroblasts induction to improve the autophagy level. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 13-44 35085453-4 2022 Rapamycin, a mechanistic target of rapamycin (mTOR) inhibitor, was added during rabbit embryonic fibroblasts induction to improve the autophagy level. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 46-50 35159256-2 2022 Rapamycin, a specific inhibitor of MTOR, has been widely used as an immunosuppressant in organ transplant patients, and its clinical application has been recently expanded to cancer therapy. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 35-39 35587661-1 2022 PURPOSE: To investigate the mechanism of microRNA-100-5p (miR-100-5p) on mammalian target (mTOR) of rapamycin in temporomandibular arthritis. Sirolimus 100-109 mechanistic target of rapamycin kinase Homo sapiens 91-95 34874016-9 2022 On the other hand, rapamycin abolished the effects of T-induced cardiac hypertrophy, decreased the systolic and diastolic blood pressure of SHR, and inhibited the activation of mTOR/ S6K1/4EBP1 signaling pathway in a concentration-dependent manner. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 177-181 35163076-6 2022 Therapeutic strategies associated with rapamycin have worked well in a number of different diseases, and there is every reason to believe that targeting components of the mTOR pathway may pay off in atherosclerosis as well. Sirolimus 39-48 mechanistic target of rapamycin kinase Homo sapiens 171-175 35499412-12 2022 In November 2021, the FDA approved nab-sirolimus (mTOR inhibitor) for PEComas. Sirolimus 39-48 mechanistic target of rapamycin kinase Homo sapiens 50-54 34904422-7 2022 Finally, we found that CP blocked the interaction of L. japonicus protein kinase B (AKT) with LjHSP90ab1 by competitively binding the NM domain of LjHSP90ab1 to inhibit the AKT-mechanistic target of the rapamycin (MTOR) pathway. Sirolimus 203-212 mechanistic target of rapamycin kinase Homo sapiens 214-218 33554444-8 2021 Inhibition of mTOR with rapamycin blocked the effects of GPR39 overexpression on protein synthesis and repressed cardiac hypertrophy. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 14-18 35087713-1 2022 Introduction: Recent studies showed that rapamycin, as a mammalian target of rapamycin (mTOR) inhibitor, could have beneficial therapeutic effects for the central nervous system (CNS) related diseases. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 57-86 35087713-1 2022 Introduction: Recent studies showed that rapamycin, as a mammalian target of rapamycin (mTOR) inhibitor, could have beneficial therapeutic effects for the central nervous system (CNS) related diseases. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 88-92 34987640-9 2022 Further, to reactivate functionally indolent TILs, we reprogrammed ex vivo TILs with Ibrutinib plus Rapamycin to block interleukin-2-inducible kinase (ITK) and mTOR pathways, respectively. Sirolimus 100-109 mechanistic target of rapamycin kinase Homo sapiens 160-164 33872697-1 2021 Activation of the protein kinase mechanistic target of rapamycin (mTOR) in both complexes 1 and 2 (mTORC1/2) in the liver is repressed during fasting and rapidly stimulated in response to a meal. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 66-70 35012940-10 2022 However, mTOR-selective inhibitors (everolimus, rapamycin) alone did not exert cytotoxic effects. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 9-13 33838212-7 2021 In addition, phosphorylation levels of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt) and mammalian rapamycin target protein (mTOR) decreased after HS treatment in early and medium stages of PD rats. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 140-144 33955513-0 2021 Rapamycin protects against aristolochic acid nephropathy in mice by potentiating mammalian target of rapamycin-mediated autophagy. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 81-110 33955513-6 2021 Mechanistically, rapamycin inhibited the renal expression of phosphorylated (p-)mammalian target of rapamycin (mTOR) and p-ribosomal S6 protein kinase 1, which in turn activated renal autophagy and decreased apoptosis, probably by removing AA-elicited damaged mitochondria and misfolded proteins. Sirolimus 17-26 mechanistic target of rapamycin kinase Homo sapiens 111-115 33955513-6 2021 Mechanistically, rapamycin inhibited the renal expression of phosphorylated (p-)mammalian target of rapamycin (mTOR) and p-ribosomal S6 protein kinase 1, which in turn activated renal autophagy and decreased apoptosis, probably by removing AA-elicited damaged mitochondria and misfolded proteins. Sirolimus 100-109 mechanistic target of rapamycin kinase Homo sapiens 111-115 33955513-7 2021 The findings of the present study demonstrated that rapamycin protects against AA-induced nephropathy by activating the mTOR-autophagy axis and suggested that rapamycin may be a promising pharmacological target for the treatment of AAN. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 120-124 33955513-7 2021 The findings of the present study demonstrated that rapamycin protects against AA-induced nephropathy by activating the mTOR-autophagy axis and suggested that rapamycin may be a promising pharmacological target for the treatment of AAN. Sirolimus 159-168 mechanistic target of rapamycin kinase Homo sapiens 120-124 33846781-5 2021 MET and the mTOR inhibitor rapamycin (RAPA) decreased the viability in control and resistant cells, and decreased the cell size increase induced by CIS. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 12-16 33846781-5 2021 MET and the mTOR inhibitor rapamycin (RAPA) decreased the viability in control and resistant cells, and decreased the cell size increase induced by CIS. Sirolimus 38-42 mechanistic target of rapamycin kinase Homo sapiens 12-16 34050114-4 2021 Previous studies have suggested that all-trans retinoic acid (atRA) and rapamycin (RAPA), an mTOR inhibitor, protect lipopolysaccharide (LPS)-induced neuronal inflammation through inhibiting nuclear import of NFkappaB. Sirolimus 72-81 mechanistic target of rapamycin kinase Homo sapiens 93-97 34050114-4 2021 Previous studies have suggested that all-trans retinoic acid (atRA) and rapamycin (RAPA), an mTOR inhibitor, protect lipopolysaccharide (LPS)-induced neuronal inflammation through inhibiting nuclear import of NFkappaB. Sirolimus 83-87 mechanistic target of rapamycin kinase Homo sapiens 93-97 33908567-0 2021 Facile synthesis of rapamycin-peptide conjugates as mTOR and Akt inhibitors. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 52-56 34048926-2 2021 The disease involves the mTOR pathway and the cutaneous manifestation responds to topical treatment with sirolimus (SIR). Sirolimus 105-114 mechanistic target of rapamycin kinase Homo sapiens 25-29 34048926-2 2021 The disease involves the mTOR pathway and the cutaneous manifestation responds to topical treatment with sirolimus (SIR). Sirolimus 116-119 mechanistic target of rapamycin kinase Homo sapiens 25-29 34003452-2 2021 Previous studies have shown that the mTOR inhibitor sirolimus can reduce complaints and improve QoL in some patients. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 37-41 34004440-8 2021 Inhibition of mTOR with rapamycin or knockdown of mTOR enhanced metformin"s suppression of hsBAFF-induced phosphorylation of S6K1, PTEN, Akt, and Erk1/2, as well as B-cell proliferation/viability. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 14-18 33128812-6 2021 Concomitant treatment with belatacept plus a mammalian target of rapamycin inhibitor (mTORi; sirolimus or everolimus) has yielded AR rates ranging from 0 to 4%. Sirolimus 93-102 mechanistic target of rapamycin kinase Homo sapiens 45-74 33888602-4 2021 We have previously shown that mechanistic/mammalian target of rapamycin (mTOR) drives cerebrovascular dysfunction in models of AD by reducing the activity of endothelial nitric oxide synthase (eNOS), and that attenuation of mTOR activity with rapamycin is sufficient to restore eNOS-dependent cerebrovascular function. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 73-77 33888602-4 2021 We have previously shown that mechanistic/mammalian target of rapamycin (mTOR) drives cerebrovascular dysfunction in models of AD by reducing the activity of endothelial nitric oxide synthase (eNOS), and that attenuation of mTOR activity with rapamycin is sufficient to restore eNOS-dependent cerebrovascular function. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 224-228 33888602-5 2021 Here we show mTOR drives NVC impairments in an AD model through the inhibition of neuronal NOS and non-NOS dependent components of NVC, and that mTOR attenuation with rapamycin is sufficient to restore NVC and even enhance it above WT responses. Sirolimus 167-176 mechanistic target of rapamycin kinase Homo sapiens 145-149 33231291-2 2021 The mTOR inhibitor sirolimus is emerging as targeted therapy in KHE. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 33952452-2 2021 The phosphatidylinositol-3-kinase/AKT serine/threonine kinase/mammalian target of rapamycin (PI3K/AKT/mTOR) signalling pathway is frequently activated in colorectal cancer (CRC). Sirolimus 82-91 mechanistic target of rapamycin kinase Homo sapiens 102-106 33922284-1 2021 BACKGROUND: Melanoma patients stop responding to targeted therapies mainly due to mitogen activated protein kinase (MAPK) pathway re-activation, phosphoinositide 3 kinase/the mechanistic target of rapamycin (PI3K/mTOR) pathway activation or stromal cell influence. Sirolimus 197-206 mechanistic target of rapamycin kinase Homo sapiens 213-217 33542495-4 2021 The mTOR inhibitor rapamycin impeded glycolysis and limited flagellin-induced secretion of immune mediators. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 33531656-6 2021 Thus, we designed a novel therapeutic approach that implements dual targeting of mTOR: direct inhibition of the mTOR protein (with rapamycin), in combination with IKAROS-mediated transcriptional repression of the MTOR gene (using the CK2 inhibitor, CX-4945). Sirolimus 131-140 mechanistic target of rapamycin kinase Homo sapiens 112-116 33913609-8 2021 Both mTOR inhibitor rapamycin and MEK inhibitor trametinib inhibited growth of the two cell lines. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 5-9 33930827-8 2021 Rapamycin, an inhibitor of mTOR, was used to study the role of mTOR signaling pathway on exosomes mediated migration of SW480 cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 33912444-0 2021 Rapamycin Antagonizes BCRP-Mediated Drug Resistance Through the PI3K/Akt/mTOR Signaling Pathway in mPRalpha-Positive Breast Cancer. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 73-77 33959512-4 2021 Rapamycin and 3BDO were used to regulate the mTOR pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 45-49 33206174-5 2021 CHIR-124, a selective CHK1 inhibitor, impairs cell viability and induces remarkable synergistic lethality with mTOR inhibitor rapamycin in MYC-overexpressing cells. Sirolimus 126-135 mechanistic target of rapamycin kinase Homo sapiens 111-115 33880473-4 2022 While rapamycin and rapamycin analogs (rapalogs) are FDA-approved for use as mTOR inhibitors in multiple clinical settings, including cancer, we previously found that rapamycin can increase the susceptibility of cells to infection by Influenza A virus. Sirolimus 6-15 mechanistic target of rapamycin kinase Homo sapiens 77-81 33880473-4 2022 While rapamycin and rapamycin analogs (rapalogs) are FDA-approved for use as mTOR inhibitors in multiple clinical settings, including cancer, we previously found that rapamycin can increase the susceptibility of cells to infection by Influenza A virus. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 77-81 33880473-4 2022 While rapamycin and rapamycin analogs (rapalogs) are FDA-approved for use as mTOR inhibitors in multiple clinical settings, including cancer, we previously found that rapamycin can increase the susceptibility of cells to infection by Influenza A virus. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 77-81 33927621-8 2021 However, these protective effects against HIBD could be suppressed when rapamycin, a specific inhibitor of mTOR, was included. Sirolimus 72-81 mechanistic target of rapamycin kinase Homo sapiens 107-111 33924197-6 2021 Autophagy inhibition by chloroquine reduced decorin mRNA levels, while autophagy activation using the mTOR inhibitor rapamycin enhanced decorin transcription. Sirolimus 117-126 mechanistic target of rapamycin kinase Homo sapiens 102-106 33902956-2 2021 Sirolimus is a typical mammalian target of rapamycin (mTOR) inhibitor, and tuberous sclerosis 1-tuberous sclerosis 2 complex (TSC1/TSC2) is an important negative effector in the mTOR pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 23-52 33902956-2 2021 Sirolimus is a typical mammalian target of rapamycin (mTOR) inhibitor, and tuberous sclerosis 1-tuberous sclerosis 2 complex (TSC1/TSC2) is an important negative effector in the mTOR pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 54-58 33902956-2 2021 Sirolimus is a typical mammalian target of rapamycin (mTOR) inhibitor, and tuberous sclerosis 1-tuberous sclerosis 2 complex (TSC1/TSC2) is an important negative effector in the mTOR pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 178-182 33935683-5 2021 This study aimed to explore whether rapamycin can ameliorate anesthesia/surgery-induced cognitive deficits by inhibiting mTOR, activating autophagy and rising synaptic plasticity-related proteins in the hippocampus. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 121-125 33540491-5 2021 We also found that LPAR5 specific antagonists TC LPA5 4, PI3K inhibitor Wortmannin or mTOR inhibitor Rapamycin pretreatment abrogated phosphorylation of Akt and p70S6K1 stimulated by LPA in CGTH-W3 and TPC-1 cells. Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 86-90 33897695-11 2021 We found rapamycin, a mTOR inhibitor, partly inhibited cell proliferation, invasion, and migration in shTOX HCT116 cells. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 22-26 33916918-8 2021 In vitro studies demonstrated that the effect of KP-Nano Rapa-loaded, in reducing the amount of the Phospo-Ser757-ULK1 protein through the inhibition of the mammalian target of rapamycin (mTOR), is comparable to that of the free drug. Sirolimus 57-61 mechanistic target of rapamycin kinase Homo sapiens 157-186 33916918-8 2021 In vitro studies demonstrated that the effect of KP-Nano Rapa-loaded, in reducing the amount of the Phospo-Ser757-ULK1 protein through the inhibition of the mammalian target of rapamycin (mTOR), is comparable to that of the free drug. Sirolimus 57-61 mechanistic target of rapamycin kinase Homo sapiens 188-192 33897381-1 2021 Hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) due to mutations in genes along the PI3K-mTOR pathway and the GATOR1 complex causes a spectrum of neurodevelopmental disorders (termed mTORopathies) associated with malformation of cortical development and intractable epilepsy. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 66-70 33839363-11 2021 Accordingly, LUAD-0061AS3 cells were more sensitive to MTOR inhibitors than MDA-MB-175-VII cells and targeting the MTOR pathway with rapamycin blocked growth of LUAD-0061AS3 PDX tumors in vivo. Sirolimus 133-142 mechanistic target of rapamycin kinase Homo sapiens 55-59 33839363-11 2021 Accordingly, LUAD-0061AS3 cells were more sensitive to MTOR inhibitors than MDA-MB-175-VII cells and targeting the MTOR pathway with rapamycin blocked growth of LUAD-0061AS3 PDX tumors in vivo. Sirolimus 133-142 mechanistic target of rapamycin kinase Homo sapiens 115-119 33962348-2 2021 A mammalian target of rapamycin (mTOR) inhibitor (mTORi), either everolimus or sirolimus, is now routinely prescribed for multiple clinical manifestations of TSC, including subependymal giant cell astrocytoma and epilepsy. Sirolimus 79-88 mechanistic target of rapamycin kinase Homo sapiens 2-31 33962348-2 2021 A mammalian target of rapamycin (mTOR) inhibitor (mTORi), either everolimus or sirolimus, is now routinely prescribed for multiple clinical manifestations of TSC, including subependymal giant cell astrocytoma and epilepsy. Sirolimus 79-88 mechanistic target of rapamycin kinase Homo sapiens 33-37 33300153-0 2021 Growth inhibition and suppression of the mTOR and Wnt/beta-catenin pathways in T-acute lymphoblastic leukemia by rapamycin and MYCN depletion. Sirolimus 113-122 mechanistic target of rapamycin kinase Homo sapiens 41-45 33826265-12 2021 Two patients were treated with mTOR inhibitors (rapamycin), with a progressive decrease in extracutaneous involvement and platelet recovery, but with a poor response in dermal lesions. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 31-35 33300153-3 2021 Rapamycin, the mTOR inhibitor, showed inhibitory effects on T-ALL cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 15-19 33300153-7 2021 Rapamycin and MYCN inhibition suppressed both Wnt/beta-catenin and mTOR signaling pathways. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 67-71 33156513-6 2021 In addition, autophagy inhibitor 3-methyladenine (3-MA) had a protective effect similar to that of AMI, but autophagy activator rapamycin eliminated the protective effect of AMI by suppressing mTOR activation. Sirolimus 128-137 mechanistic target of rapamycin kinase Homo sapiens 193-197 33534053-1 2021 The mechanistic (or mammalian) target of rapamycin (mTOR) is considered as a critical regulatory enzyme involved in essential signaling pathways affecting cell growth, cell proliferation, protein translation, regulation of cellular metabolism, and cytoskeletal structure. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 52-56 33661803-7 2021 Rapamycin, an inhibitor of mTOR, was used to further study the role of H19 in autophagy. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 33070461-4 2021 Furthermore, the evidence of an efficient T-cell alloimmunity abrogation accompanied by a sustained anti-viral response after sirolimus addition, promotes the potential benefit of converting patients to an mTOR-based immunosuppression in case of PVAN. Sirolimus 126-135 mechanistic target of rapamycin kinase Homo sapiens 206-210 33892851-5 2021 In recent decades, the identification of the responsible genes and gene products forming the mechanistic target of rapamycin complex, previously termed the mammalian target of rapamycin, not only has expanded our understanding of tuberous sclerosis pathophysiology, but has also inspired the search for targeted interventions. Sirolimus 115-124 mechanistic target of rapamycin kinase Homo sapiens 156-185 33865602-11 2021 The expression of p-mTOR, p-4EBP1, and p-P70S6K decreased and the ratio of LC-3 II/LC-3 I elevated after treatment of sirolimus. Sirolimus 118-127 mechanistic target of rapamycin kinase Homo sapiens 20-24 33865602-13 2021 Sirolimus may block mTOR-mediated pathways and induced autophagy in KHE. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 20-24 33307051-10 2021 Furthermore, the treatment efficacy of IGF were blocked with AMPA receptor inhibitor NBQX or mTOR inhibitor Rapamycin. Sirolimus 108-117 mechanistic target of rapamycin kinase Homo sapiens 93-97 33710804-12 2021 SNORA23 and rapamycin blocked the PI3K/AKT/mTOR signaling pathway and impaired HCC growth in vivo. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 43-47 33675613-3 2021 Previous studies have reported that sertraline and fluoxetine can suppress the growth of gastric carcinoma, melanoma and nonsmall cell lung cancers by inhibiting the mammalian target rapamycin (mTOR) activity. Sirolimus 183-192 mechanistic target of rapamycin kinase Homo sapiens 194-198 33691148-4 2021 Against this background, the present study aimed interfering with extinction of conditioned anti-proliferative and immunosuppressive immune responses in a taste-associative learning paradigm with the mTOR inhibitor rapamycin. Sirolimus 215-224 mechanistic target of rapamycin kinase Homo sapiens 200-204 33691148-5 2021 By pairing sub-effective doses of the US (rapamycin) as reminder cues simultaneously with the CS (taste stimulus) at retrieval, conditioned pharmacological responses of rapamycin persisted peripherally and centrally, reflected as suppressed interleukin-10 production and T cell activity as well as diminished activity of the mTOR target protein p70s6k in the amygdala. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 325-329 33691148-5 2021 By pairing sub-effective doses of the US (rapamycin) as reminder cues simultaneously with the CS (taste stimulus) at retrieval, conditioned pharmacological responses of rapamycin persisted peripherally and centrally, reflected as suppressed interleukin-10 production and T cell activity as well as diminished activity of the mTOR target protein p70s6k in the amygdala. Sirolimus 169-178 mechanistic target of rapamycin kinase Homo sapiens 325-329 33340561-8 2021 Silencing FAM135B shows synergy with PI3K/Akt/mTOR pathway inhibitor (rapamycin) in increasing radiosensitivity, regulating the expression of cell cycle protein and inducing apoptosis of ESCC cells. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 46-50 33683500-6 2021 The suppressed activation of mTOR and MEK by combined rapamycin and binimetinib treatment was confirmed using Western blot assay. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 29-33 33416457-2 2021 The mechanistic target of the rapamycin (mTOR) pathway is vital for fetal lung development and implicated in hypoxia-associated PH, yet its involvement in the developmental programming of PH remains unclear. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 41-45 33423298-2 2021 Previous studies suggest a connection between the FA protein FANCD2 and the non-FA protein mechanistic target of rapamycin (mTOR). Sirolimus 113-122 mechanistic target of rapamycin kinase Homo sapiens 124-128 33481427-8 2021 SUMMARY: The mTOR inhibitor sirolimus is the most used targeted therapy so far but new molecules are tested currently. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 13-17 32037974-1 2021 Rapamycin and their derivatives known as rapalogs, were the first-generation mTOR inhibitors which interacted with mTORC1 but not with the mTORC2 protein. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 77-81 33527306-4 2021 Recently, some researchers have suggested the therapeutic potential of mTOR inhibitors such as rapamycin against COVID-19. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 71-75 33369022-1 2021 INTRODUCTION: Sirolimus has become a pillar in the treatment of vascular anomalies due to its inhibition of the mammalian target of rapamycin (mTOR). Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 112-141 33369022-1 2021 INTRODUCTION: Sirolimus has become a pillar in the treatment of vascular anomalies due to its inhibition of the mammalian target of rapamycin (mTOR). Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 143-147 33640883-2 2021 mTOR inhibition by rapamycin can sensitize cancer cells to radiotherapy. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 0-4 33660929-2 2021 In particular, mTOR complex 1 (mTORC1) promotes protein synthesis in ribosomes by activating the downstream effectors, p70S6K and 4EBP1, in skeletal muscle and is highly sensitive to rapamycin, an mTOR inhibitor. Sirolimus 183-192 mechanistic target of rapamycin kinase Homo sapiens 15-19 33641344-3 2021 Our goal was to assess the effects of mTOR inhibition by rapamycin on inflammation, microglial activation, oxidative stress, and apoptosis associated with the changes in the inhibitor-kappaB (IkappaB)-alpha/nuclear factor-kappaB (NF-kappaB)/hypoxia-inducible factor-1alpha (HIF-1alpha) pathway activity following a systemic challenge with lipopolysaccharide (LPS). Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 38-42 33679734-2 2021 Recent findings indicate that the mammalian target of the rapamycin (mTOR)-signaling pathway is implicated in the regulation of BTB assembly and restructuring. Sirolimus 58-67 mechanistic target of rapamycin kinase Homo sapiens 69-73 32482020-3 2021 Sirolimus, a mammalian target of rapamycin(mTOR) inhibitor recently has been reported to be effective in the treatment of insulinoma and CHI patients. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 13-42 32482020-3 2021 Sirolimus, a mammalian target of rapamycin(mTOR) inhibitor recently has been reported to be effective in the treatment of insulinoma and CHI patients. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 43-47 33718332-2 2020 As such, rapamycin that inhibits the mechanistic target of rapamycin (mTOR), the downstream effector of this signaling pathway, is of great interest. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 37-68 33718332-2 2020 As such, rapamycin that inhibits the mechanistic target of rapamycin (mTOR), the downstream effector of this signaling pathway, is of great interest. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 70-74 33718332-10 2020 Interestingly, cells cultivated in normoxia (21% O2) seem to be more sensitive to mTOR inhibition by rapamycin than those cultivated in hypoxia (0.4% O2). Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 82-86 33669763-2 2021 We employed a structure-based workflow to identify new inhibitors targeting mTOR kinase at rapamycin binding site. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 76-80 33681258-13 2021 Further assessments revealed that activation of mTOR and GSK3beta was almost completely inhibited by rapamycin and SB216763, respectively, which significantly increased the caspase-3 levels. Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 48-52 33578031-11 2021 Mechanistically, BAG3 overexpression in NRVCs promoted physiological hypertrophy by activating the protein kinase B (AKT)/mammalian (or mechanistic) target of rapamycin (mTOR) pathway. Sirolimus 159-168 mechanistic target of rapamycin kinase Homo sapiens 170-174 33634164-3 2020 The presence of these populations in VAs is supported, in part, by the observed clinical effect of the mTOR inhibitor, sirolimus, that regulates differentiation of embryonic stem cells (ESCs). Sirolimus 119-128 mechanistic target of rapamycin kinase Homo sapiens 103-107 33669763-8 2021 Furthermore, the stability of the resulting complexes was studied by means of MD simulation which revealed that the selected compounds were able to form a stable ternary complex with FKBP12 and FRB domain, thus underlining their potential ability to inhibit mTOR with a rapamycin-like mechanism. Sirolimus 270-279 mechanistic target of rapamycin kinase Homo sapiens 258-262 33599151-6 2021 mTOR forms two protein complexes, mTORC1, which is sensitive to rapamycin and mTORC2, which is not directly inhibited by this drug. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 0-4 33621205-6 2021 The relevant mechanisms were related to activation of mTOR, and selective inhibition of mTOR by rapamycin could weaken the sensitization of nicardipine to temozolomide, which suggest that nicardipine can be applied as an adjuvant to inhibit autophagy in GSCs, and enhance apoptosis-promoting effect of temozolomide in GSCs as well. Sirolimus 96-105 mechanistic target of rapamycin kinase Homo sapiens 88-92 33412209-6 2021 However, U0126, a potent extracellular signal-regulated kinase 1/2 (Erk1/2) inhibitor, decreased PDGF-BB-induced LC3 expression, while rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), increased it. Sirolimus 135-144 mechanistic target of rapamycin kinase Homo sapiens 166-195 33643212-4 2021 In cell models of epilepsy and TSC, rapamycin, an mTOR inhibitor, has been shown to decrease seizure frequency and duration, and positively affect cell growth and morphology. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 50-54 32835451-6 2021 Treatment with the mTOR inhibitor rapamycin decreased astroglial VEGFR-3 expression and GLT-1 expression after SE. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 19-23 33435684-5 2021 Thus, rapamycin differentially influences protein and lipid synthesis in mTOR signaling. Sirolimus 6-15 mechanistic target of rapamycin kinase Homo sapiens 73-77 33450548-2 2021 Herein, a series of flavonol-based derivatives of fisetin, a plant-based flavonoid identified as an anti-tumorigenic agent targeting the mammalian targets of rapamycin (mTOR)-regulated pathways, were synthesized and fully characterized. Sirolimus 158-167 mechanistic target of rapamycin kinase Homo sapiens 169-173 32457486-4 2021 Both the classical autophagy inducer rapamycin and the classical ferroptosis activator RSL3 can block MTOR activation and cause GPX4 protein degradation in human pancreatic cancer cells. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 102-106 33359326-5 2021 In this study, we examined the effects of mammalian target of rapamycin (mTOR) inhibitors (rapamycin or Torin1) on the fibrotic response induced by transforming growth factor-beta 1 (TGF-beta1) in cultured human conjunctival fibroblast (HCF) cells. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 73-77 33540133-9 2021 Sirolimus, a strong inhibitor of mTOR, has shown tremendous promise in the treatment of LM, both as an oral and a topical agent. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 33-37 33337347-11 2021 ICV BMP9-induced increase in hepatic insulin sensitivity and related metabolic effects were blocked by ICV injection of rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) signaling. Sirolimus 120-129 mechanistic target of rapamycin kinase Homo sapiens 147-176 33337347-11 2021 ICV BMP9-induced increase in hepatic insulin sensitivity and related metabolic effects were blocked by ICV injection of rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) signaling. Sirolimus 120-129 mechanistic target of rapamycin kinase Homo sapiens 178-182 33183431-3 2021 Therefore, research at home and abroad is actively focusing on the mTOR signaling pathway to further clarify the pathogenesis of the disease, and from a clinical point of view, to summarize the clinical data of more patients treated with mTOR inhibitors, to conduct a long-term follow-up and exploration of rapamycin treatment, and to summarize mature treatment experience. Sirolimus 307-316 mechanistic target of rapamycin kinase Homo sapiens 67-71 33183431-3 2021 Therefore, research at home and abroad is actively focusing on the mTOR signaling pathway to further clarify the pathogenesis of the disease, and from a clinical point of view, to summarize the clinical data of more patients treated with mTOR inhibitors, to conduct a long-term follow-up and exploration of rapamycin treatment, and to summarize mature treatment experience. Sirolimus 307-316 mechanistic target of rapamycin kinase Homo sapiens 238-242 33411714-9 2021 We confirmed internalization of mf-derived EVs by human DCs and monocytes using confocal microscopy and flow cytometry, and further demonstrated through flow cytometry, that mf-derived EVs downregulate the phosphorylation of mTOR in human monocytes (THP-1 cells) to the same degree that rapamycin (a known mTOR inhibitor) does. Sirolimus 287-296 mechanistic target of rapamycin kinase Homo sapiens 225-229 33316689-3 2021 Sirolimus is an mammalian target of rapamycin inhibitor studied in other vascular anomalies and a potentially promising therapy in Sturge-Weber syndrome. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 16-45 33496749-4 2021 Activation of the mammalian target of rapamycin (mTOR) was diminished in hypoxic leukemic cells, and treatment of T-ALL with the mTOR inhibitor rapamycin in normoxia mimicked the hypoxia effects, namely decreased cell growth and increased quiescence and drug resistance. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 49-53 33496749-4 2021 Activation of the mammalian target of rapamycin (mTOR) was diminished in hypoxic leukemic cells, and treatment of T-ALL with the mTOR inhibitor rapamycin in normoxia mimicked the hypoxia effects, namely decreased cell growth and increased quiescence and drug resistance. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 129-133 33479203-9 2021 Notably, therapeutic inhibition of mTOR with rapamycin or temsirolimus induced preferential apoptosis of CSC, when compared to bulk tumor cells. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 35-39 33565716-8 2021 Rapamycin or miR-138-5p mimics similarly suppressed the activation of AKT and mTOR, whereas UCA1 overexpression exert opposite roles. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 78-82 33565716-9 2021 Interestingly, administration of rapamycin or miR-138-5p mimics apparently antagonized the effects of UCA1 on AKT and mTOR activation. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 118-122 33431351-3 2021 The discovery of this underlying mechanism paved the way for the use of a class of drugs called mTOR inhibitors including rapamycin and everolimus and specifically targeting this pathway. Sirolimus 122-131 mechanistic target of rapamycin kinase Homo sapiens 96-100 33489922-3 2020 mTOR inhibitors, such as Rapamycin and Rapamycin analogs (Rapalogs), have become a promising class of agents to treat malignant blood diseases-either alone or in combination with other treatment regimens. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 0-4 33489922-3 2020 mTOR inhibitors, such as Rapamycin and Rapamycin analogs (Rapalogs), have become a promising class of agents to treat malignant blood diseases-either alone or in combination with other treatment regimens. Sirolimus 39-48 mechanistic target of rapamycin kinase Homo sapiens 0-4 33858600-2 2021 Among many important molecular machines that lie at the intersection of this triad, the mechanistic (formerly mammalian) target of rapamycin (mTOR) is a central regulator of cell metabolism, proliferation, and survival. Sirolimus 131-140 mechanistic target of rapamycin kinase Homo sapiens 142-146 33405944-2 2021 The mTOR (mammalian target of rapamycin) inhibitor sirolimus shows promise for treating vascular anomalies, though response assessment is not standardized. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 4-8 33405944-2 2021 The mTOR (mammalian target of rapamycin) inhibitor sirolimus shows promise for treating vascular anomalies, though response assessment is not standardized. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 10-39 33419207-8 2021 Whereas RICTOR (rapamycin independent companion of mammalian target of rapamycin) was predicted to be inhibited in both WB and FE datasets, the predictions were based on different downstream molecules. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 51-80 33428109-9 2021 The mTOR inhibitor rapamycin mitigated TGF-beta-induced expression of p21, p16, and DNA damage foci and improved replicative potential of preadipocytes, supporting the cell-specific response to this cytokine. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 33858600-4 2021 Accordingly, the pharmacological implications of mTOR inhibition using rapamycin or others rapalogs span the treatment of various human diseases from immune disorders to cancer. Sirolimus 71-80 mechanistic target of rapamycin kinase Homo sapiens 49-53 32507936-9 2021 A single case report of rapamycin, an mTOR inhibitor, used as chemoprevention in FAP patients exists, but no formal clinical studies have been conducted. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 38-42 33162031-3 2021 Different from previous reports about additives treatment on recipient after ovarian transplantation, we here report a new vitrification protocol with pretreatment of rapamycin, an inhibitor of the mTOR signaling pathway. Sirolimus 167-176 mechanistic target of rapamycin kinase Homo sapiens 198-202 33384406-6 2021 Importantly, inhibition of mTOR signaling by rapamycin serves as an effective osteoanabolic therapeutic strategy to protect against TNFalpha deficiency and mechanical unloading. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 27-31 32394479-3 2021 The mTOR protein is incorporated into two distinct complexes: mammalian target of Rapamycin complex 1 (mTORC1) and mammalian target of Rapamycin complex 2 (mTORC2). Sirolimus 82-91 mechanistic target of rapamycin kinase Homo sapiens 4-8 32394479-3 2021 The mTOR protein is incorporated into two distinct complexes: mammalian target of Rapamycin complex 1 (mTORC1) and mammalian target of Rapamycin complex 2 (mTORC2). Sirolimus 135-144 mechanistic target of rapamycin kinase Homo sapiens 4-8 33372169-8 2020 Interestingly, the protective effects of MCH were blocked by the mTOR inhibitor, rapamycin. Sirolimus 81-90 mechanistic target of rapamycin kinase Homo sapiens 65-69 33278711-5 2021 mTOR inhibitor such as rapamycin are thought to induce tolerance and are used as anticancer drugs in several cancers. Sirolimus 23-32 mechanistic target of rapamycin kinase Homo sapiens 0-4 32803763-8 2021 Finally, with mTOR inhibitor rapamycin, we confirmed that NEAT1 promoted glioma activity through mTOR signaling both in vitro and in vivo. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 14-18 32803763-8 2021 Finally, with mTOR inhibitor rapamycin, we confirmed that NEAT1 promoted glioma activity through mTOR signaling both in vitro and in vivo. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 97-101 33508825-5 2021 In this patient, the modification of an immunosuppressive regimen with introduction of rapamycin (mTOR) inhibitors and withdrawal of calcineurin inhibitors (CNIs) led to the resolution of this severe condition. Sirolimus 87-96 mechanistic target of rapamycin kinase Homo sapiens 98-102 31736460-3 2021 Here we investigated whether putatively interfering with synaptic plasticity using the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, could weaken retrieved chocolate reward memories through blockade of reconsolidation. Sirolimus 107-116 mechanistic target of rapamycin kinase Homo sapiens 118-122 33189285-2 2021 The mammalian target of rapamycin/eukaryotic initiation factor 4E (mTOR/eIF4E) signaling pathway is involved in fat synthesis. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 67-71 33141044-5 2021 Although the mTOR signaling might be inhibited by rapamycin treatment, signals transmitted from the upstream pathway supports cell survival and proliferation. Sirolimus 50-59 mechanistic target of rapamycin kinase Homo sapiens 13-17 33176606-9 2021 Pretreatment with mTOR inhibitor, rapamycin, could attenuate the activation of mTOR and the secretion of RANKL in OBs. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 18-22 33176606-9 2021 Pretreatment with mTOR inhibitor, rapamycin, could attenuate the activation of mTOR and the secretion of RANKL in OBs. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 79-83 33317397-4 2020 The present study investigates the potential of therapeutic plant peptides against cellular senescence by targeting three key proteins in the ageing network - target of rapamycin (mTOR), adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 1 (SIRT1). Sirolimus 169-178 mechanistic target of rapamycin kinase Homo sapiens 180-184 33389971-3 2020 For example, mechanistic target of rapamycin (mTOR) inhibitors such as rapamycin, phenols, and flavonoids show antioxidant characteristics, while spermidine induces autophagy. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 46-50 33307758-8 2021 These findings were associated with an increase in ERK, Akt, and mTOR phosphorylation, whereas autophagy induction through mTOR/p70S6K inhibition by rapamycin significantly suppressed NO-induced cell apoptosis. Sirolimus 149-158 mechanistic target of rapamycin kinase Homo sapiens 123-127 33327255-2 2020 Although sirolimus, a mammalian target of rapamycin inhibitor, has been suggested to be effective in patients with iMCD, the long-term safety and efficacy of sirolimus on individuals with IL-6 inhibitor-resistant iMCD have not been evaluated. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 22-51 33311440-5 2020 In addition, Comp34 alone is effective in cells with secondary resistance to rapamycin, the best-known inhibitor of mTOR, and displays a greater in vivo antitumor efficacy and lower toxicity than rapamycin in TNBC xenografted models. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 116-120 32681646-1 2020 The immunosuppressant rapamycin (RAPA) inhibits mTOR (mammalian target of rapamycin) functions and is applied after allogeneic bone marrow transplantation (BMT) to attenuate the development of graft-versus-host disease (GVHD) although the cellular targets of RAPA treatment are not well defined. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 48-52 33490152-8 2020 Finally, it was shown that the application of SKP-SC-EVs could activate the Akt/mTOR/p70S6K signaling pathway that can be abolished by rapamycin. Sirolimus 135-144 mechanistic target of rapamycin kinase Homo sapiens 80-84 32985258-2 2020 Herein, we sought to explore the anti-cancer mechanisms of ISL loaded nanoliposomes (ISL-NLs) on AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathways mediated glycolysis. Sirolimus 146-155 mechanistic target of rapamycin kinase Homo sapiens 162-166 33171062-6 2020 Mechanistically, curcumin inactivates the mechanistic target of rapamycin complex 1 (mTORC1), the upstream regulator of rDNA transcription and autophagy induction, by inhibiting mTOR lysosomal localization. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 85-89 32681646-1 2020 The immunosuppressant rapamycin (RAPA) inhibits mTOR (mammalian target of rapamycin) functions and is applied after allogeneic bone marrow transplantation (BMT) to attenuate the development of graft-versus-host disease (GVHD) although the cellular targets of RAPA treatment are not well defined. Sirolimus 33-37 mechanistic target of rapamycin kinase Homo sapiens 54-83 32681646-1 2020 The immunosuppressant rapamycin (RAPA) inhibits mTOR (mammalian target of rapamycin) functions and is applied after allogeneic bone marrow transplantation (BMT) to attenuate the development of graft-versus-host disease (GVHD) although the cellular targets of RAPA treatment are not well defined. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 54-83 32681646-1 2020 The immunosuppressant rapamycin (RAPA) inhibits mTOR (mammalian target of rapamycin) functions and is applied after allogeneic bone marrow transplantation (BMT) to attenuate the development of graft-versus-host disease (GVHD) although the cellular targets of RAPA treatment are not well defined. Sirolimus 33-37 mechanistic target of rapamycin kinase Homo sapiens 48-52 33349211-1 2020 Lung toxicity is a rare but serious side effect of sirolimus, a mammalian target of rapamycin inhibitor used as an immunosuppressive agent in solid-organ transplant recipients. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 64-93 33174028-13 2020 Furthermore, depleting expression of RAGE or mTORC2 protein components (rapamycin-insensitive companion of mTOR) by small interfering RNA was found to reduce the cell viability, migration and angiogenesis of S100A8/9-treated HUVECs. Sirolimus 72-81 mechanistic target of rapamycin kinase Homo sapiens 45-49 32610114-13 2020 Rapamycin, the mTOR inhibitor, can inhibit the pro-tumorigenic effect of VEPH1-knockdown. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 15-19 32865663-4 2020 Mechanistic (formerly mammalian) target of rapamycin (mTOR), sirtuin (SIRT) and insulin/insulin growth factor 1 (IGF1) signalling pathways are among the most important pathways in ageing-associated conditions, such as neurodegeneration. Sirolimus 43-52 mechanistic target of rapamycin kinase Homo sapiens 54-58 32599680-1 2020 Therapeutics targeting the phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway initially produce potent antitumor effects, but resistance frequently occurs. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 93-97 32279604-9 2020 mTOR activity in the brain following the IF and rapamycin treatment was differentially regulated by age. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 0-4 32279604-10 2020 Interestingly, rapamycin inhibited mTOR more potently in young animals than IF. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 35-39 32157856-3 2020 mTOR inhibitor Sirolimus has been used in hyperinsulinemic hypoglycemia that was unresponsive to other medical treatment. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 0-4 32157856-14 2020 Sirolimus treatment, by mTOR inhibition, appeared to be effectively controlling the peristent hypoglycemia and could be a lifesaving tool for these kind of disorders. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 24-28 33202661-8 2020 When mTOR was inhibited directly via the macrolide rapamycin, peroxisome degradation was still partially suppressed by Ras2, while inactivation of Ras2 resulted in an enhanced degradation of peroxisomes, suggesting a role of Ras2 in the inhibition of peroxisome degradation in glucose-grown cells. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 5-9 33294353-11 2020 Rapamycin has been used in several cases based on the purported activation of the mammalian target of rapamycin (mTOR) in DIPNECH. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 82-111 33294353-11 2020 Rapamycin has been used in several cases based on the purported activation of the mammalian target of rapamycin (mTOR) in DIPNECH. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 113-117 33138632-1 2020 The drug rapamycin is a potent inhibitor of the mTOR complex, acting directly in the signaling cascade of this protein complex; interrupting cell proliferation, in addition to being an extremely efficient immunosuppressant. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 48-52 33158864-1 2020 The protein kinase mammalian target of rapamycin (mTOR) is the central regulator of cell growth. Sirolimus 39-48 mechanistic target of rapamycin kinase Homo sapiens 50-54 33237667-5 2021 Cells from patients with TED and controls were treated with rapamycin [mechanistic target of rapamycin an (mTOR) inhibitor] and MHY1485 (an mTOR stimulator) as well as inhibitors upstream in the same signaling cascade (saracatinib and befatinib). Sirolimus 60-69 mechanistic target of rapamycin kinase Homo sapiens 71-105 33237667-5 2021 Cells from patients with TED and controls were treated with rapamycin [mechanistic target of rapamycin an (mTOR) inhibitor] and MHY1485 (an mTOR stimulator) as well as inhibitors upstream in the same signaling cascade (saracatinib and befatinib). Sirolimus 60-69 mechanistic target of rapamycin kinase Homo sapiens 107-111 31931659-12 2020 Collectively, our results identify ROS as central inducers of MTORC2 activation during chronic autophagy, which in turn fuels senescence activation and myofibroblast differentiation in distinct cellular subpopulations.Abbreviations: 3-MA: 3-methyladenine; ACTA2: actin, alpha 2, smooth muscle, aorta; AKT1: AKT serine/threonine kinase 1; p-AKT1: AKT1 Ser473 phosphorylation; t-AKT1: total AKT serine/threonine kinase 1; ATG4A: autophagy related 4A cysteine peptidase; ATG7: autophagy gene 7; C12FDG: 5-dodecanoylaminofluorescein Di-beta-D-Galactopyranoside; CDKN1A: cyclin dependent kinase inhibitor 1A; CDKN2A: cyclin dependent kinase inhibitor 2A; Ctl: control; DAPI: 4",6-diamidino-2-phenylindole, dilactate; ECM: extracellular matrix; GSH: L-glutathione reduced; H2O2: hydrogen peroxide; HLF: adult human lung fibroblasts; Ho: Hoechst 33342 (2"-[4-ethoxyphenyl]-5-[4-methyl-1-piperazinyl]-2.5"-bi-1H-benzimidazole); HSC: hepatic stellate cells; LY: LY294002; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MTORC1/2: mechanistic target of rapamycin kinase complex 1/2; N: normal growth medium; NAC: N-acetyl-L-cysteine; PBS: phosphate-buffered saline; PDGFA: platelet derived growth factor subunit A; PRKCA/PKCalpha: protein kinase C alpha; PtdIns3K: class III phosphatidylinositol 3-kinase; PTEN: phosphatase and tensin homolog; R: rapamycin; RICTOR: RPTOR independent companion of MTOR complex 2; ROS: reactive oxygen species; RPTOR: regulatory associated protein of MTOR complex 1; SA-GLB1/beta-gal: senescence-associated galactosidase beta 1; SGK1: serum/glucocorticoid regulated kinase 1; shRNA: short hairpin RNA; siCtl: control siRNA; siRNA: small interfering RNA; SQSTM1: sequestosome 1; SS: serum-free (serum starvation) medium; TP53: tumor protein p53; TUBA: tubulin alpha; V: vehicle. Sirolimus 1357-1366 mechanistic target of rapamycin kinase Homo sapiens 62-66 31865844-8 2020 : intra peritoneal; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; NPHS1: nephrosis 1, nephrin; NPHS2: nephrosis 2, podocin; PLA: proximity-ligation assay; PRKAA: 5"-AMP-activated protein kinase catalytic subunit alpha; RPTOR/RAPTOR: regulatory associated protein of MTOR, complex 1; RFP: red fluorescent protein; TSC1: tuberous sclerosis 1; ULK1: unc-51 like kinase 1. Sirolimus 109-118 mechanistic target of rapamycin kinase Homo sapiens 81-85 31931659-12 2020 Collectively, our results identify ROS as central inducers of MTORC2 activation during chronic autophagy, which in turn fuels senescence activation and myofibroblast differentiation in distinct cellular subpopulations.Abbreviations: 3-MA: 3-methyladenine; ACTA2: actin, alpha 2, smooth muscle, aorta; AKT1: AKT serine/threonine kinase 1; p-AKT1: AKT1 Ser473 phosphorylation; t-AKT1: total AKT serine/threonine kinase 1; ATG4A: autophagy related 4A cysteine peptidase; ATG7: autophagy gene 7; C12FDG: 5-dodecanoylaminofluorescein Di-beta-D-Galactopyranoside; CDKN1A: cyclin dependent kinase inhibitor 1A; CDKN2A: cyclin dependent kinase inhibitor 2A; Ctl: control; DAPI: 4",6-diamidino-2-phenylindole, dilactate; ECM: extracellular matrix; GSH: L-glutathione reduced; H2O2: hydrogen peroxide; HLF: adult human lung fibroblasts; Ho: Hoechst 33342 (2"-[4-ethoxyphenyl]-5-[4-methyl-1-piperazinyl]-2.5"-bi-1H-benzimidazole); HSC: hepatic stellate cells; LY: LY294002; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MTORC1/2: mechanistic target of rapamycin kinase complex 1/2; N: normal growth medium; NAC: N-acetyl-L-cysteine; PBS: phosphate-buffered saline; PDGFA: platelet derived growth factor subunit A; PRKCA/PKCalpha: protein kinase C alpha; PtdIns3K: class III phosphatidylinositol 3-kinase; PTEN: phosphatase and tensin homolog; R: rapamycin; RICTOR: RPTOR independent companion of MTOR complex 2; ROS: reactive oxygen species; RPTOR: regulatory associated protein of MTOR complex 1; SA-GLB1/beta-gal: senescence-associated galactosidase beta 1; SGK1: serum/glucocorticoid regulated kinase 1; shRNA: short hairpin RNA; siCtl: control siRNA; siRNA: small interfering RNA; SQSTM1: sequestosome 1; SS: serum-free (serum starvation) medium; TP53: tumor protein p53; TUBA: tubulin alpha; V: vehicle. Sirolimus 1063-1072 mechanistic target of rapamycin kinase Homo sapiens 62-66 33031791-5 2020 Here, we review the potential use of rapamycin, an mTOR (Mammalian Target of Rapamycin) inhibitor that can be repurposed at low dosages for the treatment of COVID-19. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 51-55 32805499-6 2020 Further, as a drug-delivery vehicle, a rapamycin (RM)-coated eStent was designed to amplify the inhibitory effect of eStent on intimal hyperplasia through the synergistic effects of the Hippo and mammalian target of rapamycin (mTOR) signaling pathways. Sirolimus 39-48 mechanistic target of rapamycin kinase Homo sapiens 196-225 32805499-6 2020 Further, as a drug-delivery vehicle, a rapamycin (RM)-coated eStent was designed to amplify the inhibitory effect of eStent on intimal hyperplasia through the synergistic effects of the Hippo and mammalian target of rapamycin (mTOR) signaling pathways. Sirolimus 39-48 mechanistic target of rapamycin kinase Homo sapiens 227-231 33031791-5 2020 Here, we review the potential use of rapamycin, an mTOR (Mammalian Target of Rapamycin) inhibitor that can be repurposed at low dosages for the treatment of COVID-19. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 57-86 32771373-5 2020 Treatment with rapamycin (an mTOR inhibitor) inhibited some effects of PA on inflammation. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 29-33 32475067-1 2020 The rapamycin analogue everolimus (EVR) is a potent inhibitor of the mammalian target of rapamycin (mTOR) and clinically used to prevent allograft rejections as well as tumor growth. Sirolimus 4-13 mechanistic target of rapamycin kinase Homo sapiens 69-98 32475067-1 2020 The rapamycin analogue everolimus (EVR) is a potent inhibitor of the mammalian target of rapamycin (mTOR) and clinically used to prevent allograft rejections as well as tumor growth. Sirolimus 4-13 mechanistic target of rapamycin kinase Homo sapiens 100-104 33055173-2 2020 PATIENTS AND METHODS: During the dose-escalation study (ClinicalTrials.gov number: NCT01087554) with the HDAC inhibitor vorinostat and the mTOR inhibitor sirolimus (V+S), a patient with Hodgkin lymphoma refractory to nine prior therapies demonstrated a partial response (PR) lasting for 18.5 months, which promoted additional enrollment of patients with Hodgkin lymphoma as well as exploration of an alternative combination of vorinostat and mTOR inhibitor everolimus (V+E). Sirolimus 154-163 mechanistic target of rapamycin kinase Homo sapiens 139-143 32898934-1 2020 Ginsenoside Rg3, a ginsenoside isolated from Panax ginseng, can regulate autophagy via AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway. Sirolimus 136-145 mechanistic target of rapamycin kinase Homo sapiens 152-156 32871057-5 2020 In the present study, we investigated the effect of mTOR inhibition with rapamycin from different time points on human umbilical cord blood-derived CD34+ cell erythropoiesis in vitro and the underlying mechanisms. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 52-56 32703671-7 2020 Reversal of heart failure occurred after tacrolimus discontinuation and the switch to a mammalian target of rapamycin (mTOR) inhibitor: sirolimus. Sirolimus 136-145 mechanistic target of rapamycin kinase Homo sapiens 88-117 32703671-7 2020 Reversal of heart failure occurred after tacrolimus discontinuation and the switch to a mammalian target of rapamycin (mTOR) inhibitor: sirolimus. Sirolimus 136-145 mechanistic target of rapamycin kinase Homo sapiens 119-123 33149623-3 2020 Rapamycin is a new type macrocyclic lactone, which can inhibit the serine/threonine protein kinase mTOR. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 99-103 33149623-14 2020 Conclusion: The results suggested that 3-BrPA combined with rapamycin could induce cell apoptosis in NB cells by inhibiting mTOR activity. Sirolimus 60-69 mechanistic target of rapamycin kinase Homo sapiens 124-128 33149623-13 2020 Rapamycin individually discourages the mTOR signaling pathway, while combined with 3-BrPA can enhance this phenomenon and influence cell metabolism of the NB cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 39-43 32819718-2 2020 Recently, the mTOR inhibitor rapamycin and its analogs have attracted growing interests and evaluated as therapeutic agents against TNBC, in which the PI3K/AKT/mTOR pathway is often activated. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 14-18 32819718-4 2020 In this study, we found that the sensitivity of TNBC cells to rapamycin was highly dependent on the expression level of rapamycin-insensitive companion of mTOR (Rictor), a key component of the mTOR complex 2. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 155-159 32819718-6 2020 Furthermore, we showed that the suppression of Rictor expression was also effective in rapamycin-insensitive cells that had acquired resistance to mTOR kinase inhibitors. Sirolimus 87-96 mechanistic target of rapamycin kinase Homo sapiens 147-151 32819718-2 2020 Recently, the mTOR inhibitor rapamycin and its analogs have attracted growing interests and evaluated as therapeutic agents against TNBC, in which the PI3K/AKT/mTOR pathway is often activated. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 160-164 33092063-2 2020 The activation of mechanistic Target Of Rapamycin (mTor)/hypoxia inducible factor (HIF)-1 pathway can be targeted by rapamycin and irinotecan, respectively. Sirolimus 117-126 mechanistic target of rapamycin kinase Homo sapiens 18-49 33105631-9 2020 For instance, rapamycin is currently being investigated for the treatment of various vascular malformations associated with hyperactivation of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 177-206 33105631-9 2020 For instance, rapamycin is currently being investigated for the treatment of various vascular malformations associated with hyperactivation of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 217-221 33145347-10 2020 Furthermore, rapamycin reduced the expression of mTOR, whereas the promotion of LC3-II/LC3-I was blocked by the GSK3beta inhibitor TWS119. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 49-53 33092063-2 2020 The activation of mechanistic Target Of Rapamycin (mTor)/hypoxia inducible factor (HIF)-1 pathway can be targeted by rapamycin and irinotecan, respectively. Sirolimus 117-126 mechanistic target of rapamycin kinase Homo sapiens 51-55 33076974-9 2020 The mTOR inhibitor rapamycin suppresses neuronal hyperactivity, but does not increase synchronised network activity, whereas activation of AMPK restores some aspects of network activity. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 33050143-9 2020 The AKT-mammalian target of the rapamycin (mTOR) signal pathway, which is important for muscle protein synthesis, was increased in LL-administered groups. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 43-47 33173419-3 2020 Present study is aimed to assess the activity of the two mTOR inhibitors (rapamycin - RAP and sapanisertib - MLN) as a single agent and combined with gemcitabine (GEM, one of substances commonly used in systemic anticancer treatment) in uterine sarcoma and carcinosarcoma in vitro models. Sirolimus 74-83 mechanistic target of rapamycin kinase Homo sapiens 57-61 33162811-2 2020 While a well-known mTOR inhibitor, rapamycin, has been shown to reduce glioblastoma survival, the role of mitochondria in achieving this therapeutic effect is less well known. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 19-23 33076263-1 2020 Research has suggested that nutrient, exercise, and metabolism-related proteins interact to regulate mammalian target of rapamycin complex one (mTOR) post-exercise and their interactions needs clarification. Sirolimus 121-130 mechanistic target of rapamycin kinase Homo sapiens 144-148 32557381-6 2020 The mTOR inhibitor sirolimus is the most studied compound for the treatment of venous, lymphatic, and complex malformations. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 32861747-2 2020 Here to study the mechanism of the acquired resistance of MCF-7 breast cancer cells to mTOR inhibitors two different models of the cell resistance were used: rapamycin-resistant MCF-7/Rap subline developed under long-term rapamycin treatment, and metformin-resistant MCF-7/M subline obtained by long-term metformin treatment. Sirolimus 158-167 mechanistic target of rapamycin kinase Homo sapiens 87-91 32590192-7 2020 A dual-targeting delivery liposomal system was designed with dual-modification of PD-L1 nanobody and mannose ligands for co-delivering an mTOR inhibitor (rapamycin) and an anti-angiogenic drug (regorafenib). Sirolimus 154-163 mechanistic target of rapamycin kinase Homo sapiens 138-142 32457396-8 2020 Topical Rapamycin treatment improved extramammary PD-associated symptoms in humans, suggesting mTOR inhibition as a novel therapeutic treatment in PD. Sirolimus 8-17 mechanistic target of rapamycin kinase Homo sapiens 95-99 32861747-5 2020 Transfection of mir-181c, one of the positive regulators of Akt and mTOR, lead to an increase in the cell resistance to both mTOR inhibitors, rapamycin, and metformin, which correlated with Raptor overexpression and activation of Akt/AP-1 signaling. Sirolimus 142-151 mechanistic target of rapamycin kinase Homo sapiens 68-72 32747423-9 2020 Combined mTOR (rapamycin) and CDK4/6 (palbociclib) inhibition decreased tumor size and proliferation in tumor flank transplants, increased survival in an intravenous transplant model of disseminated leukemia compared to single agent treatment and cooperatively decreased cell viability in human T-ALL/LBL cell lines. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 9-13 33016658-1 2020 OBJECTIVE: Sirolimus mTOR inhibitor represents a major advance in the treatment of patients with complicated vascular abnormalities. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 21-25 33448097-8 2020 OS cell lines exhibited differential sensitivity to mTOR inhibitor Rapamycin. Sirolimus 67-76 mechanistic target of rapamycin kinase Homo sapiens 52-56 33448097-11 2020 Immunofluorescence (IF) analysis showed that mTOR is constitutively activated in the 143B cells but is suppressed in the U2OS cells, indicating that this might be their reason for being resistant to Rapamycin. Sirolimus 199-208 mechanistic target of rapamycin kinase Homo sapiens 45-49 33069284-6 2020 Advances in medical therapy through inhibition of the mTOR/PI3K/AKT pathway with Sirolimus and more proximal targeted drugs along with advances in sclerotherapy techniques are promising for the long-term improvement and amelioration of symptoms in patients with venous malformations. Sirolimus 81-90 mechanistic target of rapamycin kinase Homo sapiens 54-58 32160289-12 2020 Inhibition of the mechanistic target of the rapamycin (mTOR) pathway suppressed IFNalpha production from monocytes and downregulated enhanced STING expression and its downstream molecules. Sirolimus 44-53 mechanistic target of rapamycin kinase Homo sapiens 55-59 33193709-3 2020 It is also known that hamartin is involved as a target in the rapamycin (mTOR) signaling pathway, which functions to integrate a variety of environmental triggers in order to exert control over cellular metabolism and homeostasis. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 73-77 33004923-6 2020 In further experiments, in vitro exposure to rapamycin inhibited placental glutamine and glutamate uptake (24 h, uncomplicated pregnancies) indicating a role of mTOR in regulating placental transport of these amino acids. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 161-165 33062677-5 2020 In the present study, we investigated if Wubeizi ointment suppressed keloid formation through the modulation of key molecules of the rapamycin (mTOR) pathway including phosphatase and tensin homolog (PTEN), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt). Sirolimus 133-142 mechanistic target of rapamycin kinase Homo sapiens 144-148 33013932-3 2020 Our results show that RLR stimulation increased the phosphorylation of the mTOR complex (mTORC) 1 and mTORC2 downstream targets p70S6 kinase and Akt, respectively, and this process was prevented by the mTORC1 inhibitor rapamycin as well as the dual mTORC1/C2 kinase inhibitor AZD8055 in both DC subtypes. Sirolimus 219-228 mechanistic target of rapamycin kinase Homo sapiens 75-79 32621911-7 2020 Compared with liraglutide group, treatment with rapamycin, a specific inhibitor of mTOR, compatibly augmented GLP-1 receptor level, inhibited phosphorylation of mTOR/p70S6K and expression of p62 as well as increased level of LC3-II/LC3-I ratio and Beclin-1, suggesting that there is an interaction between GLP-1 and mTOR/p70S6K signaling in the regulation of autophagy. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 83-87 32621911-7 2020 Compared with liraglutide group, treatment with rapamycin, a specific inhibitor of mTOR, compatibly augmented GLP-1 receptor level, inhibited phosphorylation of mTOR/p70S6K and expression of p62 as well as increased level of LC3-II/LC3-I ratio and Beclin-1, suggesting that there is an interaction between GLP-1 and mTOR/p70S6K signaling in the regulation of autophagy. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 161-165 32621911-7 2020 Compared with liraglutide group, treatment with rapamycin, a specific inhibitor of mTOR, compatibly augmented GLP-1 receptor level, inhibited phosphorylation of mTOR/p70S6K and expression of p62 as well as increased level of LC3-II/LC3-I ratio and Beclin-1, suggesting that there is an interaction between GLP-1 and mTOR/p70S6K signaling in the regulation of autophagy. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 161-165 32693673-10 2020 Mechanistically, LAPTM4B regulated the activity of mammalian target of rapamycin complex 1 (mTORC1) via interacting with mTOR through its EC3 domain. Sirolimus 71-80 mechanistic target of rapamycin kinase Homo sapiens 92-96 32707053-9 2020 Moreover, the expression of Rab31-induced p-p70S6K was almost inhibited by rapamycin, a well-established inhibitor of mTOR. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 118-122 32900356-9 2021 LY294002 and rapamycin inhibited PI3K/Akt/mTOR and AQP1 expression (P<0.01), prevented the change of AQP1 location in SRA01/04 plasma membrane (P<0.01). Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 42-46 32911743-8 2020 In both HT29 and DLD-1 cells, the CSC population was significantly decreased following treatment with metformin, AMPK activator (AICAR), HMG-CoA reductase inhibitor (simvastatin), or mTOR inhibitor (rapamycin), and was increased by mevalonate. Sirolimus 199-208 mechanistic target of rapamycin kinase Homo sapiens 183-187 32867785-9 2020 Mechanically, RAPA ameliorated the physiological function of mutant ECs by inhibiting AKT-mTOR pathway, but also facilitated the nuclear location of FOXO1 and the expression of PDGFB in mutant ECs, and then improved paracrine interactions between ECs and SMCs. Sirolimus 14-18 mechanistic target of rapamycin kinase Homo sapiens 90-94 32705169-12 2020 Furthermore, IDH1-overexpressing and alpha-KG-treated U87 cells were incubated with rapamycin, an mTOR-specific inhibitor, and the results revealed that rapamycin treatment reversed the increased cell migration caused by IDH1 overexpression and alpha-KG treatment. Sirolimus 84-93 mechanistic target of rapamycin kinase Homo sapiens 98-102 32705169-12 2020 Furthermore, IDH1-overexpressing and alpha-KG-treated U87 cells were incubated with rapamycin, an mTOR-specific inhibitor, and the results revealed that rapamycin treatment reversed the increased cell migration caused by IDH1 overexpression and alpha-KG treatment. Sirolimus 153-162 mechanistic target of rapamycin kinase Homo sapiens 98-102 32428390-2 2020 Previous reports showed resolution of immune cytopenias in solid organ transplant recipients following replacement of the calcineurin inhibitor tacrolimus with the mTOR inhibitor sirolimus. Sirolimus 179-188 mechanistic target of rapamycin kinase Homo sapiens 164-168 32717360-6 2020 mTOR inhibition by rapamycin triggered FOXO3 and miR-34, leading to KLF4 repression. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 0-4 32772681-1 2020 BACKGROUND AND PURPOSE: Rapamycin is a clinically approved mammalian target of rapamycin inhibitor that has been shown to be neuroprotective in animal models of stroke. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 59-88 32776229-3 2020 Several reports indicate that the inhibitor of mTOR rapamycin can reverse GC resistance, but the molecular mechanism involved in this synergistic effect has not been fully defined. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 47-51 32847614-6 2020 Moreover, both MA-TAM master regulators and their target genes are significantly correlated with poor clinical outcomes and are often associated with genomic aberrations in neurofibromin 1 (NF1) and phosphoinositide 3-kinases/mammalian target of rapamycin/Akt pathway (PI3K-mTOR-AKT)-related genes. Sirolimus 246-255 mechanistic target of rapamycin kinase Homo sapiens 274-278 32825760-6 2020 We have demonstrated metformin"s ability to enhance the cytostatic activity of the tamoxifen and rapamycin on both parent MCF-7 cells and MCF-7-resistant derivates mediated via the suppression of mTOR signaling and growth-related transcriptional factors. Sirolimus 97-106 mechanistic target of rapamycin kinase Homo sapiens 196-200 32843029-11 2020 We prescribed sirolimus, which is an oral mTOR inhibitor, for two consecutive years. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 42-46 32526201-6 2020 Western blot results showed that NEP down-regulates the production of phospho-mammalian target of rapamycin (p-mTOR), whereas increases the expression of key autophagy-related molecules such as Beclin-1, Atg5-Atg12, and LC3-II. Sirolimus 98-107 mechanistic target of rapamycin kinase Homo sapiens 111-115 32531316-0 2020 Resveratrol potentiates the anti-tumor effects of rapamycin in papillary thyroid cancer: PI3K/AKT/mTOR pathway involved. Sirolimus 50-59 mechanistic target of rapamycin kinase Homo sapiens 98-102 32850379-8 2020 Deoxyshikonin inactivated the protein kinase B (Akt)/mammalian target of the rapamycin (mTOR) pathway. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 88-92 32823598-8 2020 In the present study, we mitigated the effects of IR-induced inflammatory EVs (i.e., TNF-alpha), through the use of mTOR inhibitors (mTORi; Rapamycin and INK128). Sirolimus 140-149 mechanistic target of rapamycin kinase Homo sapiens 116-120 32335491-1 2020 BACKGROUND: We performed a retrospective study on the efficacy and safety of sirolimus (an mTOR inhibitor) in hormone receptor (HR)-positive advanced breast cancer and searched for biomarkers to predict its efficacy. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 91-95 32335491-10 2020 For patients who received less than 3 lines of chemotherapy, those with PI3K/Akt/mTOR pathway alterations had a better response to sirolimus than those without alterations, with a median PFS of 7.0 months vs 4.3 months (hazard ratio = 0.01, 95% CI 0.00-0.34, P = 0.010). Sirolimus 131-140 mechanistic target of rapamycin kinase Homo sapiens 81-85 32416459-3 2020 Of note, first-generation mTOR inhibitors are mainly reported to be rapamycin and its derivatives and second-generation mTOR inhibitors that consist of several ATP-competitive kinase inhibitors. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 26-30 32057805-3 2020 A major pathway leading to senescence is via the activation of PI3 kinase-mammalian target of rapamycin (mTOR) signaling. Sirolimus 94-103 mechanistic target of rapamycin kinase Homo sapiens 105-109 31900833-8 2020 The suppression of the autophagic flux inhibited the apoptosis of compound C-treated U937 and U937/HQ cells, whereas co-treatment with rapamycin, a mTOR inhibitor, sensitized the two cell lines to compound C cytotoxicity. Sirolimus 135-144 mechanistic target of rapamycin kinase Homo sapiens 148-152 32416459-4 2020 Interestingly, the third-generation mTOR inhibitor, RapaLink-1, mediates rapamycin and mTOR kinase inhibitors via the same molecule and shows much higher efficiency. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 36-40 32849956-8 2020 Conclusions: Since many tumors are characterized by deregulated PI3K/AKT/mTOR pathway, rapamycin is thought to inhibit the pathway and tumor growth. Sirolimus 87-96 mechanistic target of rapamycin kinase Homo sapiens 73-77 32742319-13 2020 Of note, calcineurin, cyclosporin A, mTOR inhibitor rapamycin and NFATC2-specific small interfering RNA restored the function of SOCE in p.R304W-mutant BMDMs. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 37-41 32850534-0 2020 Early Adjuvant Medication With the mTOR Inhibitor Sirolimus in a Preterm Neonate With Compressive Cystic Lymphatic Malformation. Sirolimus 50-59 mechanistic target of rapamycin kinase Homo sapiens 35-39 32696949-9 2020 In addition, p-mTOR and p-GSK-3beta were up-regulated by RES and down-regulated by RAPA and SB216763. Sirolimus 83-87 mechanistic target of rapamycin kinase Homo sapiens 15-19 32850534-3 2020 An mTOR inhibitor, sirolimus, was started from the first day of life, and was combined with iterative sclerotherapy procedures. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 3-7 32683410-13 2020 Finally, treatment with rapamycin (an mTOR inhibitor) was shown to abolish the increased proliferation capability of DM1 SSCs due to MBNL1 overexpression. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 38-42 32711543-4 2020 Although sirolimus known as a mTOR inhibitor has good response to FAVA, expression pattern of the mTOR pathway was still unclear. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 30-34 32774365-2 2020 Sirolimus as a mammalian target of rapamycin inhibitor may be helpful in patients with CHI who do not respond well to other treatments including diazoxide and octreotide. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 15-44 32766308-12 2020 In addition, rapamycin, the mTOR inhibitor, has cooperative effect with minocycline on suppression of TNF-alpha release and induction of autophagy by repressing mTOR. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 28-32 32766308-12 2020 In addition, rapamycin, the mTOR inhibitor, has cooperative effect with minocycline on suppression of TNF-alpha release and induction of autophagy by repressing mTOR. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 161-165 32668776-1 2020 Background and objectives: Everolimus (EVE) is a mammalian target of the rapamycin (mTOR) inhibitor that is widely used in cancer patients. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 84-88 32344255-6 2020 To test this, rapamycin, an mTOR inhibitor, was used. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 28-32 32676162-4 2020 We found high mTOR signaling activity in the cultured cells, which were sensitive to a small molecule inhibitor, rapamycin, a suppressor of the mTOR pathway. Sirolimus 113-122 mechanistic target of rapamycin kinase Homo sapiens 14-18 32676162-4 2020 We found high mTOR signaling activity in the cultured cells, which were sensitive to a small molecule inhibitor, rapamycin, a suppressor of the mTOR pathway. Sirolimus 113-122 mechanistic target of rapamycin kinase Homo sapiens 144-148 32676162-5 2020 Suppressed mTOR signaling after treatment with rapamycin was confirmed by decreased phosphorylation of the S6 ribosomal protein. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 11-15 32630768-3 2020 The discovery of mTOR signaling started from isolation of rapamycin in 1975 and cloning of TOR genes in 1993. Sirolimus 58-67 mechanistic target of rapamycin kinase Homo sapiens 17-21 32348869-8 2020 Finally, we observed that rapamycin, an mTOR inhibitor, blocked both the MK-801-induced increases in phosphorylated mTOR and the MK-801 facilitating effect on memory consolidation. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 40-44 32348869-8 2020 Finally, we observed that rapamycin, an mTOR inhibitor, blocked both the MK-801-induced increases in phosphorylated mTOR and the MK-801 facilitating effect on memory consolidation. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 116-120 32753891-13 2020 Protein microarray and Western blot verification showed that activity of Akt/mammalian target of rapamycin/eukaryotic translation initiation factor 4E binding protein 1 (Akt/mTOR/4EBP1) pathway was downregulated along with RRM2 downregulation. Sirolimus 97-106 mechanistic target of rapamycin kinase Homo sapiens 174-178 32541317-2 2020 Indeed, they harbour loss of function of TSC1/TSC2, which lead to the activation of the mammalian target of rapamycin (mTOR) pathway, which is targetable therapeutically with mTOR inhibitors like sirolimus. Sirolimus 196-205 mechanistic target of rapamycin kinase Homo sapiens 88-117 32524929-3 2020 More recently, those invasive or challenging tumours have been successfully treated with mammalian target of rapamycin inhibitors, typically everolimus and sirolimus. Sirolimus 156-165 mechanistic target of rapamycin kinase Homo sapiens 89-118 32541317-2 2020 Indeed, they harbour loss of function of TSC1/TSC2, which lead to the activation of the mammalian target of rapamycin (mTOR) pathway, which is targetable therapeutically with mTOR inhibitors like sirolimus. Sirolimus 196-205 mechanistic target of rapamycin kinase Homo sapiens 119-123 32541317-2 2020 Indeed, they harbour loss of function of TSC1/TSC2, which lead to the activation of the mammalian target of rapamycin (mTOR) pathway, which is targetable therapeutically with mTOR inhibitors like sirolimus. Sirolimus 196-205 mechanistic target of rapamycin kinase Homo sapiens 175-179 32319590-8 2020 Furthermore, it was found that the energy metabolism of cervical cancer cells was inhibited following treatment with the mTOR inhibitor rapamycin. Sirolimus 136-145 mechanistic target of rapamycin kinase Homo sapiens 121-125 32352655-7 2020 Higher reactivity to the mTOR complex 1 activation marker, phospho-ribosomal protein S6, was associated with a better lung function response to rapamycin (p = 0.0001). Sirolimus 144-153 mechanistic target of rapamycin kinase Homo sapiens 25-29 32409220-2 2020 Drugs that inhibit the mTOR pathway, such as sirolimus, can reduce the size of both SGCTs and AMLs. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 23-27 32352655-10 2020 Markers of mTOR activation predict the response to rapamycin, suggesting that more advanced LAM may be less mTOR responsive and treatments specifically targeted towards LAM associated fibroblasts may have roles as adjuncts to mTOR inhibition. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 11-15 32386481-9 2020 More important, preconditioning with PI3K/AKT inhibitor LY294002 or mTOR inhibitor rapamycin both aggravated KLK10 knockdown-suppressed cancer cell growth and glucose metabolism. Sirolimus 83-92 mechanistic target of rapamycin kinase Homo sapiens 68-72 32404282-8 2020 HRG blocked the inhibitory effect of mTOR inhibitors, such as rapamycin and everolimus, on cell growth but not that of a PI3K inhibitor. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 37-41 32027426-4 2020 Cell lines derived from NF1-related tumours have shown to be sensitive to the mTOR inhibitor rapamycin. Sirolimus 93-102 mechanistic target of rapamycin kinase Homo sapiens 78-82 32323340-3 2020 Sirolimus, an mTOR inhibitor, is a promising drug for the treatment of vascular malformations and vascular tumors. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 32391547-0 2020 Lowe syndrome patient cells display mTOR- and RhoGTPase-dependent phenotypes alleviated by rapamycin and statins. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 36-40 32642630-3 2020 CDK4/6 inhibitor monotherapy is ineffective due to RAS-mediated activation of alternative pathways, including phosphatidylinositol 3-kinase-mammalian target of rapamycin (PI3K-mTOR). Sirolimus 160-169 mechanistic target of rapamycin kinase Homo sapiens 176-180 32580379-5 2020 The mammalian target of rapamycin/ribosomal S6 kinase (mTOR/S6K) pathway is blocked in these conditions, and we provide evidence that this is mediated by modulation of both the 5" AMP-activated protein kinase (AMPK) and phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathways. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 55-59 32670280-16 2020 Inhibition of mTOR in purified NK cells from healthy donors by rapamycin decreased the synthesis of IFN-gamma. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 14-18 32488108-10 2020 The mTOR inhibitor rapamycin inhibited AP-induced DC-SIGN expression, CD4+ Th1/Th17 cell differentiation and the pro-inflammatory response via Myc. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 32513927-6 2020 Combined inhibition of VEGF-C and the PI3K downstream target mTOR using Rapamycin, but neither treatment alone, promotes regression of lesions. Sirolimus 72-81 mechanistic target of rapamycin kinase Homo sapiens 61-65 32512849-1 2020 Progressive bladder cancer growth is associated with abnormal activation of the mammalian target of the rapamycin (mTOR) pathway, but treatment with an mTOR inhibitor has not been as effective as expected. Sirolimus 104-113 mechanistic target of rapamycin kinase Homo sapiens 115-119 32512849-1 2020 Progressive bladder cancer growth is associated with abnormal activation of the mammalian target of the rapamycin (mTOR) pathway, but treatment with an mTOR inhibitor has not been as effective as expected. Sirolimus 104-113 mechanistic target of rapamycin kinase Homo sapiens 152-156 32488108-5 2020 The mTOR inhibitor rapamycin was administered before AP induction. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 31996011-7 2020 For rats in the EA+Rapa group, rapamycin, a mammalian target of rapamycin (mTor) pathway inhibitor, was injected intramuscularly (1 mg/kg/day) near the site of crush injury in the sciatic nerve and an equivalent amount of dimethyl sulfoxide was injected in the other three groups every other day. Sirolimus 31-40 mechanistic target of rapamycin kinase Homo sapiens 44-73 31996011-7 2020 For rats in the EA+Rapa group, rapamycin, a mammalian target of rapamycin (mTor) pathway inhibitor, was injected intramuscularly (1 mg/kg/day) near the site of crush injury in the sciatic nerve and an equivalent amount of dimethyl sulfoxide was injected in the other three groups every other day. Sirolimus 31-40 mechanistic target of rapamycin kinase Homo sapiens 75-79 32184097-8 2020 The treatment with AKT1/2 inhibitor and the mTOR inhibitor rapamycin abolished CBD protective effects. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 44-48 32236601-6 2020 Furthermore, inhibition of the mTOR signaling pathway by rapamycin or knockdown of mTOR suppressed neural differentiation. Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 31-35 32067331-1 2020 The mammalian target of rapamycin (mTOR) inhibitor sirolimus is an effective treatment for difficult-to-treat lymphatic anomalies. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 35-39 32469178-3 2020 Therein, we investigated clinical manifestations of APDS1 and collected data on the efficacy and safety profile of sirolimus, a mammalian target of rapamycin inhibitor and pathway-specific targeted medicine. Sirolimus 115-124 mechanistic target of rapamycin kinase Homo sapiens 128-157 32067331-1 2020 The mammalian target of rapamycin (mTOR) inhibitor sirolimus is an effective treatment for difficult-to-treat lymphatic anomalies. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 4-33 32505499-5 2020 The anemia was successfully treated with an intense course of corticosteroids ands witch of immunosuppressive therapy from a calcineurin inhibitor to sirolimus, a mammalian target of rapamycin inhibitor. Sirolimus 150-159 mechanistic target of rapamycin kinase Homo sapiens 163-192 32523648-1 2020 PURPOSE: Metformin combined with the mTOR inhibitor rapamycin showed potential synergistic anti-tumor activity in preclinical studies in pancreatic ductal adenocarcinoma (PDA). Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 37-41 32347294-3 2020 As the mTOR name implies it is the target of natural product called rapamycin, a clinically approved drug used to treat human disease. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 7-11 32460884-3 2020 The aim of this study was to determine if the addition of ACr to BCAAs can enhance MPS and activate expression of the mammalian target of the rapamycin (mTOR) pathway compared to BCAAs and exercise alone in exercise-trained rats. Sirolimus 142-151 mechanistic target of rapamycin kinase Homo sapiens 153-157 32509933-8 2020 Furthermore Runx2+/- mice exhibited delayed and suppressed expression of mammalian target of rapamycin (mTOR) and rapamycin-insensitive companion of mTOR (Rictor), essential factors of mTORC2, which is regulated by Runx2 to phosphorylate Akt to regulate cell proliferation and differentiation, in osteoblasts on the tension side of tooth movement in vivo and in vitro. Sirolimus 93-102 mechanistic target of rapamycin kinase Homo sapiens 104-108 32422996-9 2020 In particular, the data suggest an action mechanism for molecules including Chitosan and macrolides such as the mTOR (mammalian target of Rapamycin) pathway inhibitor Rapamycin. Sirolimus 138-147 mechanistic target of rapamycin kinase Homo sapiens 112-116 32444668-4 2020 We observed reduced mTOR signalling and proliferation in human parietal epithelial cells after rapamycin treatment. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 20-24 32444674-10 2020 AMPK inhibits mTOR, and the mTOR inhibitor rapamycin also decreases NaCT expression. Sirolimus 43-52 mechanistic target of rapamycin kinase Homo sapiens 28-32 32424120-1 2020 Rapamycin inhibits protein translation in cells, including neural stem cells (NSCs), by suppressing the mechanistic target of rapamycin (mTOR). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 104-135 32424120-1 2020 Rapamycin inhibits protein translation in cells, including neural stem cells (NSCs), by suppressing the mechanistic target of rapamycin (mTOR). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 137-141 32206779-4 2020 We previously reported three anti-IL-6 non-responders with increased mTOR activation who responded to mTOR inhibition with sirolimus. Sirolimus 123-132 mechanistic target of rapamycin kinase Homo sapiens 69-73 32206779-4 2020 We previously reported three anti-IL-6 non-responders with increased mTOR activation who responded to mTOR inhibition with sirolimus. Sirolimus 123-132 mechanistic target of rapamycin kinase Homo sapiens 102-106 32206779-8 2020 Further, the degree of mTOR activation in iMCD was comparable to autoimmune lymphoproliferative syndrome, a disease driven by mTOR hyperactivation that responds to sirolimus treatment. Sirolimus 164-173 mechanistic target of rapamycin kinase Homo sapiens 23-27 32206779-8 2020 Further, the degree of mTOR activation in iMCD was comparable to autoimmune lymphoproliferative syndrome, a disease driven by mTOR hyperactivation that responds to sirolimus treatment. Sirolimus 164-173 mechanistic target of rapamycin kinase Homo sapiens 126-130 32206779-12 2020 These findings support mTOR activation as a novel therapeutic target for iMCD, which is being investigated through a trial of sirolimus (NCT03933904). Sirolimus 126-135 mechanistic target of rapamycin kinase Homo sapiens 23-27 32045600-5 2020 Moreover, Nar increases the phosphorylation levels of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt) and mammalian rapamycin target protein (mTOR). Sirolimus 129-138 mechanistic target of rapamycin kinase Homo sapiens 155-159 32369692-3 2020 We have previously shown that Tacrolimus (FK506) exerts a more potent pro-apoptotic and anti-proliferative effects than the mammalian target of rapamycin (mTOR) inhibitors (Sirolimus and Everolimus) in liver cancer cells. Sirolimus 173-182 mechanistic target of rapamycin kinase Homo sapiens 124-153 32369692-3 2020 We have previously shown that Tacrolimus (FK506) exerts a more potent pro-apoptotic and anti-proliferative effects than the mammalian target of rapamycin (mTOR) inhibitors (Sirolimus and Everolimus) in liver cancer cells. Sirolimus 173-182 mechanistic target of rapamycin kinase Homo sapiens 155-159 32369692-9 2020 The inhibition of the mTOR pathway by Sirolimus and Everolimus was related to an induction of autophagy; and at a high dose, these drugs impaired translation likely at a very early step of the elongation phase. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 22-26 32031317-5 2020 Here, we present a case of rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, in treating recurrent IVL. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 40-69 32375443-1 2020 Objective: To exploer the effect of mammalian target ofrapamycin(mTOR)on cognitive dysfunction of mice with Alzheimer"s disease (AD) induced by amyloid beta(1-42) (Abeta(1-42)) via observing the regulation effect of rapamycin on Homer3 in hippocampus. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 65-69 32031317-5 2020 Here, we present a case of rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, in treating recurrent IVL. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 71-75 31943518-2 2020 This study aimed to investigate the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway in sepsis-induced leucine resistance and its upstream signals, and to seek a way to correct leucine resistance in sepsis. Sirolimus 85-94 mechanistic target of rapamycin kinase Homo sapiens 101-105 32384426-2 2020 We identified pathophysiology of a neurodegenerative disorder in PDS patient derived cochlear cells that were induced via induced pluripotent stem cells and found sirolimus, an mTOR inhibitor, as an inhibitor of cell death with the minimum effective concentration less than 1/10 of the approved dose for other diseases. Sirolimus 163-172 mechanistic target of rapamycin kinase Homo sapiens 177-181 32231246-10 2020 Instead, we find that steatohepatitis in OTULIN-deficient livers is associated with aberrant mTOR activation, and inhibition of mTOR by rapamycin administration significantly reduces the liver pathology. Sirolimus 136-145 mechanistic target of rapamycin kinase Homo sapiens 128-132 31990892-3 2020 Sirolimus, which inhibits mammalian target of rapamycin, a regulator of cell growth and vascular endothelial growth factor expression, has successfully treated systemic vascular malformations. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 26-55 32029275-7 2020 Intriguingly, mTOR inhibitor Rapamycin was incapable to reverse this damped autophagy and EPC damage. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 14-18 32313883-2 2020 Rapamycin is a bacterial product that can inhibit mTOR via the PI3K/AKT/mTOR pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 50-54 32313883-2 2020 Rapamycin is a bacterial product that can inhibit mTOR via the PI3K/AKT/mTOR pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 72-76 31950225-8 2020 Importantly, NK cell treatment with the PI3K or mTOR inhibitors, idelalisib and rapamycin, respectively, prevents the enhanced cytokine responsiveness, thus, highlighting the relevance of the PI3K/mTOR axis in CD16-dependent priming. Sirolimus 80-89 mechanistic target of rapamycin kinase Homo sapiens 48-52 31950225-8 2020 Importantly, NK cell treatment with the PI3K or mTOR inhibitors, idelalisib and rapamycin, respectively, prevents the enhanced cytokine responsiveness, thus, highlighting the relevance of the PI3K/mTOR axis in CD16-dependent priming. Sirolimus 80-89 mechanistic target of rapamycin kinase Homo sapiens 197-201 32145384-10 2020 Furthermore, mTOR inhibition by rapamycin or serum starvation reduced ectopic expression of CCND1.tv.-derived CCND1 protein, but not 5"-UTR less CCND1-derived CCND1 protein in HEK293 cells, suggesting that the protein expression of CCND1.tv. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 13-17 32090494-6 2020 Inhibition of mTOR with rapamycin reversed LA-induced inactivation of autophagy and abolished LA-induced suppression of A549 cell viability. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 14-18 32256773-13 2020 The findings suggest that rapamycin can ameliorate kidney injury induced by AAI via blockade of mTOR, and thus could be a therapeutic strategy for patients with CAAN. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 96-100 32273566-5 2020 In the present study, we evaluated the effect of mTOR inhibition by rapamycin on the cellular function of human cardiac progenitor cells and discovered that treatment with rapamycin markedly attenuated replicative cell senescence in human cardiac progenitor cells (hCPCs) and promoted their cellular functions. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 49-53 32273566-5 2020 In the present study, we evaluated the effect of mTOR inhibition by rapamycin on the cellular function of human cardiac progenitor cells and discovered that treatment with rapamycin markedly attenuated replicative cell senescence in human cardiac progenitor cells (hCPCs) and promoted their cellular functions. Sirolimus 172-181 mechanistic target of rapamycin kinase Homo sapiens 49-53 32273566-6 2020 Furthermore, rapamycin not only inhibited mTOR signaling but also influenced signaling pathways, including STAT3 and PIM1, in hCPCs. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 42-46 31985020-5 2020 Flow cytometry was used to detect the expression of adiponectin receptor 1 (AdipoR1) and the phosphorylation of the mechanistic target of rapamycin kinase (mTOR) pathway-associated proteins mTOR and eukaryotic translation initiation factor 4E-binding protein (4EBP1). Sirolimus 138-147 mechanistic target of rapamycin kinase Homo sapiens 156-160 31985020-5 2020 Flow cytometry was used to detect the expression of adiponectin receptor 1 (AdipoR1) and the phosphorylation of the mechanistic target of rapamycin kinase (mTOR) pathway-associated proteins mTOR and eukaryotic translation initiation factor 4E-binding protein (4EBP1). Sirolimus 138-147 mechanistic target of rapamycin kinase Homo sapiens 190-194 32124948-9 2020 Pretreatment with the mTOR phosphorylation inhibitor rapamycin affected the autophagy of MPPa-PDT-induced osteosarcoma MG-63 cells and enhanced apoptosis through targeting mTOR. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 22-26 31925925-3 2020 Here, we describe three patients who received therapy with the mTOR inhibitor sirolimus with improvement in clinical symptoms, imaging, and overall well-being. Sirolimus 78-87 mechanistic target of rapamycin kinase Homo sapiens 63-67 32124948-9 2020 Pretreatment with the mTOR phosphorylation inhibitor rapamycin affected the autophagy of MPPa-PDT-induced osteosarcoma MG-63 cells and enhanced apoptosis through targeting mTOR. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 172-176 32256210-9 2020 The signaling pathway was analyzed with western blot and mTOR was inhibited with rapamycin. Sirolimus 81-90 mechanistic target of rapamycin kinase Homo sapiens 57-61 32279296-8 2020 Sirolimus, an mTOR inhibitor, has been approved for LAM treatment in the United States and many other countries. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 32296709-4 2020 Sirolimus (SRL) is a mammalian target of rapamycin (mTOR) inhibitor that has been demonstrated to inhibit lymphocyte activity, indicating potential for SRL in treatment of ITP. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 21-50 32296709-4 2020 Sirolimus (SRL) is a mammalian target of rapamycin (mTOR) inhibitor that has been demonstrated to inhibit lymphocyte activity, indicating potential for SRL in treatment of ITP. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 52-56 32296709-4 2020 Sirolimus (SRL) is a mammalian target of rapamycin (mTOR) inhibitor that has been demonstrated to inhibit lymphocyte activity, indicating potential for SRL in treatment of ITP. Sirolimus 11-14 mechanistic target of rapamycin kinase Homo sapiens 21-50 32296709-4 2020 Sirolimus (SRL) is a mammalian target of rapamycin (mTOR) inhibitor that has been demonstrated to inhibit lymphocyte activity, indicating potential for SRL in treatment of ITP. Sirolimus 11-14 mechanistic target of rapamycin kinase Homo sapiens 52-56 32296709-4 2020 Sirolimus (SRL) is a mammalian target of rapamycin (mTOR) inhibitor that has been demonstrated to inhibit lymphocyte activity, indicating potential for SRL in treatment of ITP. Sirolimus 152-155 mechanistic target of rapamycin kinase Homo sapiens 52-56 32296709-5 2020 Activation of the mTOR pathway in autoimmune diseases suggests that SRL might be a useful agent for treating ITP. Sirolimus 68-71 mechanistic target of rapamycin kinase Homo sapiens 18-22 32256210-15 2020 Finally, we showed that inhibition of mTOR with rapamycin blocked the effects of JMJD2A on protein synthesis, cell proliferation and colony formation of glioma cells. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 38-42 31887337-3 2020 Earlier studies demonstrated the important role of the mammalian targets of the rapamycin (MTOR) signaling pathway in the activation of primordial follicles and suggested that treatment with the MTOR inhibitor rapamycin could maintain the follicle pool in rodents. Sirolimus 80-89 mechanistic target of rapamycin kinase Homo sapiens 91-95 32309446-6 2020 Western blotting was used to examine autophagy and mammalian target of rapamycin/P70S6 kinase (mTOR/p70S6K) pathway-related proteins. Sirolimus 71-80 mechanistic target of rapamycin kinase Homo sapiens 95-99 32257249-4 2020 Patient underwent surgical resection of the primary lesion in the abdomen and sigmoid colon followed by adjuvant therapy with the mTOR inhibitor, sirolimus. Sirolimus 146-155 mechanistic target of rapamycin kinase Homo sapiens 130-134 31887337-3 2020 Earlier studies demonstrated the important role of the mammalian targets of the rapamycin (MTOR) signaling pathway in the activation of primordial follicles and suggested that treatment with the MTOR inhibitor rapamycin could maintain the follicle pool in rodents. Sirolimus 80-89 mechanistic target of rapamycin kinase Homo sapiens 195-199 31887337-3 2020 Earlier studies demonstrated the important role of the mammalian targets of the rapamycin (MTOR) signaling pathway in the activation of primordial follicles and suggested that treatment with the MTOR inhibitor rapamycin could maintain the follicle pool in rodents. Sirolimus 210-219 mechanistic target of rapamycin kinase Homo sapiens 91-95 31887337-3 2020 Earlier studies demonstrated the important role of the mammalian targets of the rapamycin (MTOR) signaling pathway in the activation of primordial follicles and suggested that treatment with the MTOR inhibitor rapamycin could maintain the follicle pool in rodents. Sirolimus 210-219 mechanistic target of rapamycin kinase Homo sapiens 195-199 32231197-2 2020 Rapamycin, an mTOR kinase inhibitor, and also a potent autophagy inducer, could not only effectively reverse glucocorticoid resistance, but also promote autophagy in the ALL cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 31913698-7 2020 Inhibition of the kinase mTOR (rapamycin, palomid, siRNA), which is normally associated with cell growth, reduces VSOAC activity synergistically to TSA. Sirolimus 31-40 mechanistic target of rapamycin kinase Homo sapiens 25-29 32231197-7 2020 RESULTS: Inhibition of mTOR by rapamycin could reverse glucocorticoid resistance in CEM-C1 cells, and also induce autophagy in these cells by up-regulation of LC3-II and Beclin-1 expressions. Sirolimus 31-40 mechanistic target of rapamycin kinase Homo sapiens 23-27 31931362-10 2020 In vitro, our results showed that DHA could downregulate the mammalian target of rapamycin/ribosomal protein S6 kinase beta-1 (mTOR/S6K1) signaling pathway, promote cell autophagy, and ameliorate cell proliferation in aIgA1-induced HMCs. Sirolimus 81-90 mechanistic target of rapamycin kinase Homo sapiens 127-131 32114433-3 2020 We have previously shown that rapamycin inhibits p-mTOR to repress PS1 transcription and Notch 1-signaling. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 49-55 32114433-6 2020 We now report that rapamycin inhibits the phosphorylation of both mTOR (p-mTOR) and JNK (p-JNK). Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 66-70 32114433-6 2020 We now report that rapamycin inhibits the phosphorylation of both mTOR (p-mTOR) and JNK (p-JNK). Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 74-78 31884111-10 2020 Inhibition of AKT/mTOR signaling by MK2206 or rapamycin attenuates the PRMT6-mediated EMC progression. Sirolimus 46-55 mechanistic target of rapamycin kinase Homo sapiens 18-22 31894316-3 2020 There are two classes of mTOR inhibitors: i) The rapalogs, such as rapamycin, which bind to the 12-kDa FK506-binding protein/rapamycin-binding domain of mTOR; and ii) the ATP-competitive inhibitors, such as AZD8055, which block the mTOR kinase domain. Sirolimus 67-76 mechanistic target of rapamycin kinase Homo sapiens 25-29 32006551-5 2020 Transcription assays of calcineurin (CaN)- and mTOR (mammalian target of rapamycin)-downstream target genes confirm that BbFKBP12 is the target of both FK506 and rapamycin, associated with CaN- and mTOR-signal pathways in B. bassiana. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 47-51 32087218-4 2020 METHODS AND RESULTS: Western blotting, quantitative PCR, and a dual-luciferase reporter assay indicated that mTOR inhibitors rapamycin and torin 1 upregulated IRF-1 expression and increased its transcriptional activity. Sirolimus 125-134 mechanistic target of rapamycin kinase Homo sapiens 109-113 31837522-4 2020 Sirolimus, a mTOR inhibitor, acts by inhibiting the T-cell proliferation and the release of inflammatory cytokines, have been widely investigated for its potential role in the treatment of PSED. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 13-17 31894316-3 2020 There are two classes of mTOR inhibitors: i) The rapalogs, such as rapamycin, which bind to the 12-kDa FK506-binding protein/rapamycin-binding domain of mTOR; and ii) the ATP-competitive inhibitors, such as AZD8055, which block the mTOR kinase domain. Sirolimus 67-76 mechanistic target of rapamycin kinase Homo sapiens 153-157 31894316-3 2020 There are two classes of mTOR inhibitors: i) The rapalogs, such as rapamycin, which bind to the 12-kDa FK506-binding protein/rapamycin-binding domain of mTOR; and ii) the ATP-competitive inhibitors, such as AZD8055, which block the mTOR kinase domain. Sirolimus 67-76 mechanistic target of rapamycin kinase Homo sapiens 153-157 31894316-3 2020 There are two classes of mTOR inhibitors: i) The rapalogs, such as rapamycin, which bind to the 12-kDa FK506-binding protein/rapamycin-binding domain of mTOR; and ii) the ATP-competitive inhibitors, such as AZD8055, which block the mTOR kinase domain. Sirolimus 125-134 mechanistic target of rapamycin kinase Homo sapiens 25-29 31894316-3 2020 There are two classes of mTOR inhibitors: i) The rapalogs, such as rapamycin, which bind to the 12-kDa FK506-binding protein/rapamycin-binding domain of mTOR; and ii) the ATP-competitive inhibitors, such as AZD8055, which block the mTOR kinase domain. Sirolimus 125-134 mechanistic target of rapamycin kinase Homo sapiens 153-157 31894316-3 2020 There are two classes of mTOR inhibitors: i) The rapalogs, such as rapamycin, which bind to the 12-kDa FK506-binding protein/rapamycin-binding domain of mTOR; and ii) the ATP-competitive inhibitors, such as AZD8055, which block the mTOR kinase domain. Sirolimus 125-134 mechanistic target of rapamycin kinase Homo sapiens 153-157 31863766-5 2020 In this study, we found that rapamycin (an mTOR inhibitor) and p70S6K siRNA diminished thrombin-induced IL-8/CXCL8 release. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 43-47 31769520-5 2020 In contrast, mTOR inhibitors rapamycin and AZD2014 did not induce apoptosis in SVEC cells. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 13-17 32070029-5 2020 The inhibition of the mTOR pathway by currently available pharmacological compounds (i.e., sirolimus or everolimus) is able to hamper tumor progression both in vitro and in animal models. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 22-26 32125970-1 2020 INRODUCTION: The mechanistic target of rapamycin inhibitors (mTORi) sirolimus and everolimus stabilize lung function in patients with pulmonary lymphangioleiomyomatosis (LAM) but do not induce remission. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 17-48 32194539-0 2019 mTOR Blockade by Rapamycin in Spondyloarthritis: Impact on Inflammation and New Bone Formation in vitro and in vivo. Sirolimus 17-26 mechanistic target of rapamycin kinase Homo sapiens 0-4 32194539-4 2019 Therefore, the inhibition of mTOR (with rapamycin) could be a promising therapeutic avenue in SpA. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 29-33 32075941-1 2020 Epilepsy treatments for patients with mechanistic target of rapamycin (mTOR) disorders, such as tuberous sclerosis complex (TSC) or focal cortical dysplasia type II (FCDII), are urgently needed. Sirolimus 60-69 mechanistic target of rapamycin kinase Homo sapiens 71-75 32054043-4 2020 The immunosuppressant drug rapamycin and its analogs that inhibit mTOR are currently being evaluated for their potential as anti-cancer agents, albeit with limited efficacy. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 66-70 31895414-2 2020 Objective: To evaluate the clinical response to the mammalian target of rapamycin (mTOR) inhibitor sirolimus and/or the epidermal growth factor receptor (EGFR) inhibitor erlotinib among patients with Olmsted syndrome. Sirolimus 99-108 mechanistic target of rapamycin kinase Homo sapiens 52-81 32014025-9 2020 Recent studies have demonstrated a satisfactory efficacy of sirolimus, an inhibitor of mammalian target of rapamycin, in the treatment of KHE. Sirolimus 60-69 mechanistic target of rapamycin kinase Homo sapiens 87-116 32127188-0 2020 Eosinophilic Fasciitis Triggered by Nivolumab: A Remarkable Efficacy of the mTOR Inhibitor Sirolimus. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 76-80 31895414-2 2020 Objective: To evaluate the clinical response to the mammalian target of rapamycin (mTOR) inhibitor sirolimus and/or the epidermal growth factor receptor (EGFR) inhibitor erlotinib among patients with Olmsted syndrome. Sirolimus 99-108 mechanistic target of rapamycin kinase Homo sapiens 83-87 31862477-18 2020 In contrast, everolimus, temsirolimus, and sirolimus are larger molecules (MW 1000) that bind to FK506 binding protein-12 (FKBP-12) to generate a complex that inhibits the mammalian target of rapamycin (mTOR) protein kinase complex. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 174-203 31966066-10 2020 The implication of phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR) in Ca-125 modulation was investigated using specific inhibitors. Sirolimus 105-114 mechanistic target of rapamycin kinase Homo sapiens 125-129 31667906-11 2020 The rates of p/t-p70S6K, p/t-mammalian target of rapamycin (mTOR) and p/t-adenosine monophosphate-activated protein kinase (AMPK) were raised by BB and suppressed by silencing miR-153 under TNF-alpha induced condition. Sirolimus 49-58 mechanistic target of rapamycin kinase Homo sapiens 60-64 31862477-18 2020 In contrast, everolimus, temsirolimus, and sirolimus are larger molecules (MW 1000) that bind to FK506 binding protein-12 (FKBP-12) to generate a complex that inhibits the mammalian target of rapamycin (mTOR) protein kinase complex. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 205-209 32329644-5 2020 Rapamycin pre-treatment with Naringin showed significant decrease in mTOR phosphorylation and increase in LC3B activation in AGS cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 69-73 31941840-2 2020 To elucidate the effects of 2 commonly used agents, the calcineurin inhibitor tacrolimus (TAC) and the mTOR inhibitor sirolimus (SIR), on islet function and test whether these effects could be reversed or prevented, we investigated human islets transplanted into immunodeficient mice treated with TAC or SIR at clinically relevant levels. Sirolimus 118-127 mechanistic target of rapamycin kinase Homo sapiens 103-107 31941840-2 2020 To elucidate the effects of 2 commonly used agents, the calcineurin inhibitor tacrolimus (TAC) and the mTOR inhibitor sirolimus (SIR), on islet function and test whether these effects could be reversed or prevented, we investigated human islets transplanted into immunodeficient mice treated with TAC or SIR at clinically relevant levels. Sirolimus 129-132 mechanistic target of rapamycin kinase Homo sapiens 103-107 31838137-7 2020 Importantly, we found that HBO reduced excessive autophagy in the prefrontal cortex, which was evidenced by activating of the mammalian target of the rapamycin (mTOR) and 4E-BP1, as well as suppression of LC3II and ATG5. Sirolimus 150-159 mechanistic target of rapamycin kinase Homo sapiens 161-165 32047421-9 2020 The brown fat-like phenotype in 3T3-L1 adipocytes induced by Res was possibly mediated by activation of mammalian target of rapamycin (mTOR), as brown adipocyte-specific markers were decreased by rapamycin, an inhibitor of mTOR and the MHY1485 treatment, an activator of mTOR, showed the similar effect of Res on browning markers. Sirolimus 124-133 mechanistic target of rapamycin kinase Homo sapiens 135-139 31693798-3 2020 We have previously shown that the mechanistic/mammalian target of rapamycin (mTOR) drives disease progression in mouse models of AD and in models of cognitive impairment associated with atherosclerosis, closely recapitulating vascular cognitive impairment. Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 77-81 31947591-1 2020 Studies of the mechanistic (mammalian) target of rapamycin inhibitors (mTOR) represent a step towards the targeted treatment of gynecological cancers. Sirolimus 49-58 mechanistic target of rapamycin kinase Homo sapiens 71-75 31633763-8 2020 Moreover, flow cytometry and immunoblotting analyses demonstrated that A151 is able to reverse mTOR phosphorylation comparably to the well-known mTOR inhibitor rapamycin. Sirolimus 160-169 mechanistic target of rapamycin kinase Homo sapiens 145-149 31936065-2 2020 These insights in the biological pathways have resulted in the development of multiple agents targeting vascular endothelial growth factor (VEGF), as well as inhibitors of the mammalian target of the rapamycin (mTOR) pathway. Sirolimus 200-209 mechanistic target of rapamycin kinase Homo sapiens 211-215 31782272-1 2020 BACKGROUND: Rapamycin inhibits the mammalian target of rapamycin (mTOR) activity and has been proven effective for the treatment of lung injury. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 35-64 31782272-1 2020 BACKGROUND: Rapamycin inhibits the mammalian target of rapamycin (mTOR) activity and has been proven effective for the treatment of lung injury. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 66-70 31611063-6 2020 Interestingly, this autophagy promotion concurred with enhanced anabolic activation via AKT-mammalian target of rapamycin (mTOR)-p70S6K signaling cascade and enhanced antioxidant capacity such as copper zinc superoxide dismutase (CuZnSOD), glutathione peroxidase (GPX), and peroxiredoxin 3 (PRX3), known to be as antagonists of autophagy. Sirolimus 112-121 mechanistic target of rapamycin kinase Homo sapiens 123-127 32356448-0 2020 Investigation of the effects of rapamycin on the mTOR pathway and apoptosis in metastatic and non-metastatic human breast cancer cell lines. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 49-53 31663933-2 2020 Although mTOR inhibitors are usually well tolerated, their adverse effects have been reported: sirolimus treatment in transplant patients has been rarely reported to be associated with lymphedema of the skin and subcutaneous tissues, whereas the use of everolimus seemed to be less burdened by this type of adverse effect. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 9-13 33268702-8 2020 Accordingly, YZFDF increased the expression of the phosphorylated mammalian targets of rapamycin (mTOR), leading to inhibition of autophagy (downregulated LC3 and upregulated P62). Sirolimus 87-96 mechanistic target of rapamycin kinase Homo sapiens 98-102 32356448-1 2020 AIM: The aim of this study was to analyze the effects of rapamycin treatment on apoptosis via mTOR pathway in metastatic and non-metastatic human breast cancer cell lines by immunohistochemical and TUNEL analysis. Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 94-98 32356448-8 2020 In addition, the demonstration and confirmation of increased apoptosis in Rapamycin treated groups suggested that Rapamycin, an inhibitor of mTOR, is promising in the treatment of breast cancer (Tab. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 141-145 31567652-1 2020 BACKGROUND: Rapamycin is a type of immunosuppressive agent that acts through inhibition of mammalian target of rapamycin (mTOR). Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 91-120 33028104-8 2020 Moreover, inhibition of the mammalian target of rapamycin (mTOR) activity by rapamycin influenced the effects of GASAL1 on cell proliferation, invasion, and apoptosis. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 59-63 32640952-6 2020 The mTOR-inhibitors (sirolimus, everolimus) are use rarely in pediatrics because of common side effects and no evidence of a benefit over calcineurin inhibitors. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 4-8 31896113-12 2020 The KHE pattern of expression [PTEN (-), TSC2 (-), p-mTOR (+), p-P70S6K (+), and p-4EBP1 (+)] suggested that sirolimus may be a good therapeutic choice. Sirolimus 109-118 mechanistic target of rapamycin kinase Homo sapiens 53-57 31621069-6 2020 This study yielded 35 small cell-permeable compounds with a reproducible inhibitory effect on B-cell activation and plasmablast formation, among which was the clinically applied mTOR inhibitor rapamycin. Sirolimus 193-202 mechanistic target of rapamycin kinase Homo sapiens 178-182 31567652-1 2020 BACKGROUND: Rapamycin is a type of immunosuppressive agent that acts through inhibition of mammalian target of rapamycin (mTOR). Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 122-126 31605630-7 2020 Pretreatment of LY294002 (a PI3K inhibitor) or rapamycin (an mTOR inhibitor) markedly reduced EGF-induced motility and p-AKT/p-mTOR/c-Jun/Sp1 expression when combined with melatonin. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 61-65 30794726-2 2020 However, the side effects associated with long-term rapamycin treatment, many of which are due to inhibition of a second mTOR complex, mTORC2, have seemed to preclude the routine use of rapamycin as a therapy for age-related diseases. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 121-125 30794726-2 2020 However, the side effects associated with long-term rapamycin treatment, many of which are due to inhibition of a second mTOR complex, mTORC2, have seemed to preclude the routine use of rapamycin as a therapy for age-related diseases. Sirolimus 186-195 mechanistic target of rapamycin kinase Homo sapiens 121-125 31801817-10 2020 To confirm the role of mTOR activation, we found that rapamycin diminished the effect of pembrolizumab-mediated downregulation of FOXP3. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 23-27 31605630-7 2020 Pretreatment of LY294002 (a PI3K inhibitor) or rapamycin (an mTOR inhibitor) markedly reduced EGF-induced motility and p-AKT/p-mTOR/c-Jun/Sp1 expression when combined with melatonin. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 127-131 31493485-6 2019 To understand the mechanism by which rapamycin differentially inhibits the mTOR complexes in the cancer cells, we present a mathematical model of rapamycin mode of action based on the first explanation, i.e., Le Chatelier"s principle. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 75-79 32579497-5 2020 Mammalian target to rapamycin complex 1 (mTORC1), another form of mTOR complex regulates translation of synaptic proteins involved in alcohol-induced plasticity. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 41-45 31493485-6 2019 To understand the mechanism by which rapamycin differentially inhibits the mTOR complexes in the cancer cells, we present a mathematical model of rapamycin mode of action based on the first explanation, i.e., Le Chatelier"s principle. Sirolimus 146-155 mechanistic target of rapamycin kinase Homo sapiens 75-79 31493485-8 2019 This model shows that rapamycin has stronger effects on mTORC1 compared with mTORC2, simply due to its direct interaction with free mTOR and mTORC1, but not mTORC2, without the need to consider other components that might further stabilize mTORC2. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 56-60 31848319-2 2019 Compounds that block mTOR signaling and eIF4F complex formation, such as rapamycin and its analogs, have been used in combination therapies to enhance cell killing, although their success has been limited. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 21-25 31870254-7 2019 Although rapamycin inhibited mTOR (mammalian target of rapamycin) signaling, it failed to enhance the autophagy and to ameliorate the severity of AKI caused by ischemia or cisplatin-induced nephrotoxicity. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 29-33 31817676-4 2019 The elucidation of the regulation and functions of mTOR can be traced to the discovery of the natural compound, rapamycin. Sirolimus 112-121 mechanistic target of rapamycin kinase Homo sapiens 51-55 31817676-5 2019 Studies using rapamycin have unraveled the role of mTOR in the control of cell growth and metabolism. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 51-55 31847908-4 2019 Sirolimus is an inhibitor of mammalian target of rapamycin (mTOR) involved in angio-lymphangiogenesis. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 29-58 31847908-4 2019 Sirolimus is an inhibitor of mammalian target of rapamycin (mTOR) involved in angio-lymphangiogenesis. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 60-64 31835352-5 2019 mechanistic target of rapamycin (mTOR)is the core hub regulating autophagy, which is subject to different upstream signaling pathways to regulate autophagy. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 33-37 31817676-10 2019 Since rapamycin does not fully inhibit mTOR activity, new compounds have been engineered to inhibit the catalytic activity of mTOR to more potently block its functions. Sirolimus 6-15 mechanistic target of rapamycin kinase Homo sapiens 126-130 31870254-7 2019 Although rapamycin inhibited mTOR (mammalian target of rapamycin) signaling, it failed to enhance the autophagy and to ameliorate the severity of AKI caused by ischemia or cisplatin-induced nephrotoxicity. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 35-64 31512504-2 2019 To gain therapeutic levels of Tregs there is a need to expand obtained cells ex vivo, usually in the presence of the mTOR inhibitor Rapamycin due to its ability to suppress proliferation of non-Treg T cells, thus promoting a purer Treg yield. Sirolimus 132-141 mechanistic target of rapamycin kinase Homo sapiens 117-121 31732331-3 2019 A growing body of preclinical evidence in in vitro and rodent model systems suggests that mTOR signaling may be altered in status epilepticus (SE) and that modulation of mTOR activation with mTOR inhibitors such as rapamycin (sirolimus) could provide new therapeutic avenues for treatment of both refractory epilepsy and SE. Sirolimus 215-224 mechanistic target of rapamycin kinase Homo sapiens 90-94 31732331-3 2019 A growing body of preclinical evidence in in vitro and rodent model systems suggests that mTOR signaling may be altered in status epilepticus (SE) and that modulation of mTOR activation with mTOR inhibitors such as rapamycin (sirolimus) could provide new therapeutic avenues for treatment of both refractory epilepsy and SE. Sirolimus 215-224 mechanistic target of rapamycin kinase Homo sapiens 170-174 31732331-3 2019 A growing body of preclinical evidence in in vitro and rodent model systems suggests that mTOR signaling may be altered in status epilepticus (SE) and that modulation of mTOR activation with mTOR inhibitors such as rapamycin (sirolimus) could provide new therapeutic avenues for treatment of both refractory epilepsy and SE. Sirolimus 215-224 mechanistic target of rapamycin kinase Homo sapiens 170-174 31732331-3 2019 A growing body of preclinical evidence in in vitro and rodent model systems suggests that mTOR signaling may be altered in status epilepticus (SE) and that modulation of mTOR activation with mTOR inhibitors such as rapamycin (sirolimus) could provide new therapeutic avenues for treatment of both refractory epilepsy and SE. Sirolimus 226-235 mechanistic target of rapamycin kinase Homo sapiens 90-94 31732331-3 2019 A growing body of preclinical evidence in in vitro and rodent model systems suggests that mTOR signaling may be altered in status epilepticus (SE) and that modulation of mTOR activation with mTOR inhibitors such as rapamycin (sirolimus) could provide new therapeutic avenues for treatment of both refractory epilepsy and SE. Sirolimus 226-235 mechanistic target of rapamycin kinase Homo sapiens 170-174 31732331-3 2019 A growing body of preclinical evidence in in vitro and rodent model systems suggests that mTOR signaling may be altered in status epilepticus (SE) and that modulation of mTOR activation with mTOR inhibitors such as rapamycin (sirolimus) could provide new therapeutic avenues for treatment of both refractory epilepsy and SE. Sirolimus 226-235 mechanistic target of rapamycin kinase Homo sapiens 170-174 31089971-15 2019 CONCLUSION: Based on the pharmacokinetic profiles observed, the nano-amorphous formulation could be a better alternative to Rapamune for the treatment of mammalian target of rapamycin-responsive malignancies. Sirolimus 124-132 mechanistic target of rapamycin kinase Homo sapiens 155-184 31636463-4 2019 The hypoxic tumor microenvironment drove the sustained activation of mechanistic target of rapamycin-GTPase dynamin-related protein 1 (mTOR-Drp1) in NK cells, resulting in excessive mitochondrial fission into fragments. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 135-139 31761958-3 2019 To determine whether rapamycin, an FDA-approved drug targeting the mechanistic target of rapamycin (mTOR) complex, can reduce senescence and markers of aging in human skin, an exploratory, placebo-controlled, interventional trial was conducted in a clinical dermatology setting. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 67-98 31761958-3 2019 To determine whether rapamycin, an FDA-approved drug targeting the mechanistic target of rapamycin (mTOR) complex, can reduce senescence and markers of aging in human skin, an exploratory, placebo-controlled, interventional trial was conducted in a clinical dermatology setting. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 100-104 31381473-2 2019 Clinical researches have shown that rapamycin, a specific inhibitor of mTOR, is effective in treating LMs. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 71-75 31606937-2 2019 While sirolimus, another mammalian target of rapamycin [mTOR] inhibitor had been used off-label for many years prior to the approval of EVR, the latter"s shorter terminal half-life and quicker time to steady-state trough level resulted in the requirement for no loading dose and easier dosing. Sirolimus 6-15 mechanistic target of rapamycin kinase Homo sapiens 25-54 31606937-2 2019 While sirolimus, another mammalian target of rapamycin [mTOR] inhibitor had been used off-label for many years prior to the approval of EVR, the latter"s shorter terminal half-life and quicker time to steady-state trough level resulted in the requirement for no loading dose and easier dosing. Sirolimus 6-15 mechanistic target of rapamycin kinase Homo sapiens 56-60 30782087-7 2019 The importance of Tregs at the time of embryo implantation has been well established and immunotherapy treatments, such as rapamycin (mammalian target of rapamycin inhibitor), may prove to be an effective treatment for patients with RPL, RIF, or unexplained infertility with low Treg. Sirolimus 123-132 mechanistic target of rapamycin kinase Homo sapiens 134-163 31350329-1 2019 LESSONS LEARNED: This is the first human interventional study in patients with Cowden syndrome that is driven by inactivation of germline PTEN gene.Single-agent sirolimus, a mTOR inhibitor, suppressed mTOR signaling in surrogate human tissues without significant toxicity. Sirolimus 161-170 mechanistic target of rapamycin kinase Homo sapiens 174-178 31350329-1 2019 LESSONS LEARNED: This is the first human interventional study in patients with Cowden syndrome that is driven by inactivation of germline PTEN gene.Single-agent sirolimus, a mTOR inhibitor, suppressed mTOR signaling in surrogate human tissues without significant toxicity. Sirolimus 161-170 mechanistic target of rapamycin kinase Homo sapiens 201-205 31350329-14 2019 CONCLUSION: A 56-day course of sirolimus was well tolerated in subjects with Cowden syndrome and was associated with some evidence of improvement in symptoms, skin and GI lesions, cerebellar function, and decreased mTOR signaling. Sirolimus 31-40 mechanistic target of rapamycin kinase Homo sapiens 215-219 31552622-8 2019 Previous work has also demonstrated that inhibition of the mTOR pathway, via rapamycin, altered total levels of BZLF1 transcripts. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 59-63 31733794-2 2019 We examined whether the calcineurin inhibitor tacrolimus (TAC) and the mammalian target of rapamycin (mtor) inhibitor sirolimus (SRL) inhibit Tfh cell differentiation, and affect subsequent B-cell functions. Sirolimus 118-127 mechanistic target of rapamycin kinase Homo sapiens 71-100 31739256-2 2019 Rapamycin is a potent inhibitor of mammalian target of rapamycin (mTOR) with various applications. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 35-64 31739256-2 2019 Rapamycin is a potent inhibitor of mammalian target of rapamycin (mTOR) with various applications. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 66-70 31852644-8 2019 Compared with the menthol-treated cells, the cells treated with both menthol and rapamycin showed significantly decreased TNF- alpha, IL-1beta, and p-mTOR expression and obviously lowered intracellular Ca2+ concentration (P < 0.05). Sirolimus 81-90 mechanistic target of rapamycin kinase Homo sapiens 150-154 31591157-8 2019 Finally, we found that treatment of iPSC-derived neurons with rapamycin reduced neuronal activity and partially reversed gene expression abnormalities, demonstrating that mTOR dysregulation contributes to both phenotypes. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 171-175 31704693-9 2019 These results allow for several conclusions as to how mTOR inhibition by rapamycin affects a developing organism. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 54-58 31717694-5 2019 Targeting PKM2 affected the protein kinase B (AKT)/mechanistic target of the rapamycin 1 (mTOR) pathway, and downregulated the expression of glycolytic enzymes, including lactate dehydrogenase A and glucose transporter-1, and other downstream signaling key proteins. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 90-94 31747377-8 2019 It inhibited Akt-mammalian target of rapamycin (mTOR) signaling pathway and also downregulated the expression of essential proteins that are involved in tumorigenesis such as cyclin D1, cyclooxygenase 2 (COX2), survivin, matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor-A (VEGF-A). Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 48-52 31748639-8 2019 Inhibition of mTOR signalling with rapamycin reduced the expression of endogenous VIP and of VIP-induced S6 phosphorylation. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 14-18 31540687-7 2019 The mTOR inhibitor rapamycin and mTOR siRNA blocked the TNF-alpha-induced up-regulation of DC-SIGN expression. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 31695068-3 2019 It has been shown that manipulating the mTOR (mammalian target of rapamycin) pathway using rapamycin or its analogue CCI-779 can improve the cellular and behavioural phenotypes of HD models. Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 40-44 31695068-4 2019 Ribosomal protein S6 kinase 1 (S6K1) is a major downstream signalling molecule of mTOR, and its activity is reduced by rapamycin suggesting that deregulation of S6K1 activity may be beneficial in HD. Sirolimus 119-128 mechanistic target of rapamycin kinase Homo sapiens 82-86 31271885-2 2019 Sirolimus is a mammalian target of rapamycin inhibitor that has proven effective in GVHD prophylaxis in combination with a calcineurin inhibitor, such as tacrolimus. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 15-44 31750334-10 2019 Radical surgical resection constitutes the treatment of choice for localized disease, while mammalian target of the rapamycin (mTOR) inhibitors constitute the most promising therapy for disseminated disease. Sirolimus 116-125 mechanistic target of rapamycin kinase Homo sapiens 127-131 31685878-10 2019 Alterations in SHFYNG patient fibroblast lines and iPSC-derived neurons are rescued by treatment with the mTOR inhibitor rapamycin. Sirolimus 121-130 mechanistic target of rapamycin kinase Homo sapiens 106-110 31781682-2 2019 Sirolimus, a mTOR inhibitor, is reported to allow growth of functional Tregs; here, we investigated the efficacy of low-dose sirolimus combined with conventional immunosuppressants (sirolimus immunoregulation therapy) for RA treatment with lower side effects and better tolerance. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 13-17 31297862-11 2019 Therefore, our findings provide a rationale for rapamycin treatment of NBR1-knockdown human urothelial cancer through the regulation of autophagy and mitochondrial dysfunction by regulating the AMPK/mTOR signaling pathway, indicating that NBR1 can be a potential therapeutic target of human urothelial cancer. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 199-203 31388935-4 2019 A systematic drug combination screen was subsequently performed to identify that AEE788, an inhibitor targeting multiple receptor tyrosine kinases (RTKs) EGFR/HER2 and VEGFR, synergizes with selective mTOR inhibitor rapamycin as well as its analogs (rapalogs) temsirolimus and everolimus to inhibit TNBC cell proliferation. Sirolimus 216-225 mechanistic target of rapamycin kinase Homo sapiens 201-205 31485623-12 2019 Promotion of KLK12 overexpression-induced cell viability was reversed by 5-aminoimidazole-4-carboxamide ribonucleotide, an activator of the AMPK signaling pathway, and rapamycin, a specific inhibitor of the mTOR signaling pathway. Sirolimus 168-177 mechanistic target of rapamycin kinase Homo sapiens 207-211 32128100-10 2019 In addition, eupafolin promoted expression of PI3K/AKT/mTOR signaling pathway and mTOR inhibitor rapamycin reversed the inhibitory effects on LPS-induced cardiomyocyte autophagy. Sirolimus 97-106 mechanistic target of rapamycin kinase Homo sapiens 82-86 31277013-10 2019 Pretreatment with rapamycin significantly aggravated intestinal injury evidenced by increased Chiu"s score, intestinal mucosal wet-to-dry ratio and lactic acid level, increased autophagy level evidenced by increased autophagosomes and LC3-II/LC3-I and decreased expression of p62, and downregulated expression of p-mTOR/mTOR. Sirolimus 18-27 mechanistic target of rapamycin kinase Homo sapiens 315-319 31277013-10 2019 Pretreatment with rapamycin significantly aggravated intestinal injury evidenced by increased Chiu"s score, intestinal mucosal wet-to-dry ratio and lactic acid level, increased autophagy level evidenced by increased autophagosomes and LC3-II/LC3-I and decreased expression of p62, and downregulated expression of p-mTOR/mTOR. Sirolimus 18-27 mechanistic target of rapamycin kinase Homo sapiens 320-324 31640284-5 2019 RESULTS: Rapamycin and cetuximab inhibited the mTOR/HIF-1alpha axis, and sensitized the SQ20B cell line to EGFR-inhibition. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 47-51 31351920-9 2019 Pharmacological activators of PPARalpha and AMPK had minor effects, while the mTOR inhibitor rapamycin potentiated the effect of TTA. Sirolimus 93-102 mechanistic target of rapamycin kinase Homo sapiens 78-82 31736762-0 2019 Rapamycin Attenuates High Glucose-Induced Inflammation Through Modulation of mTOR/NF-kappaB Pathways in Macrophages. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 77-81 31736762-7 2019 Rapamycin reduced NLRP3 inflammasome activation by inhibiting mTOR phosphorylation and NF-kappaB activation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 62-66 31736762-9 2019 Conclusion: Rapamycin can ameliorate high glucose-induced NLRP3 inflammasome activation by attenuating the mTOR/NF-kappaB signaling pathway in macrophages. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 107-111 30805585-13 2019 To screen the potential drug candidates, the gene expression profile of the GCPR module was mapped connectivity map (Cmap), and the mTOR inhibitor (Sirolimus) was found to be the most promising candidate. Sirolimus 148-157 mechanistic target of rapamycin kinase Homo sapiens 132-136 31624262-2 2019 In a melanoma patient in whom programmed-death 1 (PD-1) blockade resulted in organ rejection and colitis, the addition of the mTOR inhibitor sirolimus resulted in ongoing anti-tumor efficacy while promoting allograft tolerance. Sirolimus 141-150 mechanistic target of rapamycin kinase Homo sapiens 126-130 31627299-3 2019 We previously established that irinotecan has antiangiogenic properties and it is known that new mammalian target of rapamycin (mTOR) catalytic AZD inhibitors, unlike rapamycin, target both mTORC1 and mTORC2. Sirolimus 117-126 mechanistic target of rapamycin kinase Homo sapiens 128-132 32181277-4 2020 It is important to differentiate APDS from the usual polygenic CVID in view of the availability of targeted therapy like mTOR inhibitors such as Rapamycin and selective PI3Kdelta inhibitors. Sirolimus 145-154 mechanistic target of rapamycin kinase Homo sapiens 121-125 31762815-12 2019 Rapamycin, an mTOR antagonist, compromised DHA-induced autophagy. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 31434610-4 2019 In addition, whether rapamycin, a specific blocker of the mTOR signaling pathway, plays a therapeutic role by inhibiting lymphocyte metabolism remains unclear. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 58-62 31434610-9 2019 By inhibiting the mTOR signaling pathway, rapamycin could ameliorate the phenotype of the immune-mediated AA model and inhibit the proliferation of T cells by preventing cell cycle transition from G0 to G1 phase. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 18-22 31434610-11 2019 We confirmed that mitochondrial oxidative phosphorylation is involved in the metabolic reprogramming of T cells in AA and further extended the mechanism of rapamycin in treating AA by inhibiting the mTOR signaling pathway. Sirolimus 156-165 mechanistic target of rapamycin kinase Homo sapiens 199-203 31582727-6 2019 We revealed that circCDR1as enhanced autophagy in OSCC cells via inhibition of rapamycin (mTOR) activity and upregulation of AKT and ERK1/2 pathways. Sirolimus 79-88 mechanistic target of rapamycin kinase Homo sapiens 90-94 31236744-8 2019 Meanwhile, rapamycin, a specific inhibitor of mTORC1, was co-applied with gentamicin to verify the role of mTOR signaling. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 46-50 31575848-11 2019 Tivantinib (1 mumol/L) in combination with PI3K inhibitor LY294002 (0.5 mumol/L) and mTOR inhibitor rapamycin (0.1 nmol/L) largely inhibited the proliferation of glioblastoma cells. Sirolimus 100-109 mechanistic target of rapamycin kinase Homo sapiens 85-89 33911648-8 2019 Although the evidence is limited, topical mammalian target of rapamycin inhibitors such as sirolimus (rapamycin) are effective in facial angiofibroma treatment. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 42-71 30864227-12 2019 The combination of HMGB1 short interference (si) RNA and the autophagy activator rapamycin protected against podocyte apoptosis and EMT progression by inhibiting the AKT/mTOR and TGF-beta/smad signaling pathway, respectively. Sirolimus 81-90 mechanistic target of rapamycin kinase Homo sapiens 170-174 30864227-13 2019 CONCLUSIONS: Although HMGB1 siRNA and rapamycin treatment had opposite effects on autophagy and AKT/mTOR signaling, there was no contradiction about the role of HMGB1 siRNA and rapamycin on AKT/mTOR pathway because autophagy and AKT/mTOR signaling play dual roles in intracellular biological processes. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 100-104 31524635-5 2019 Treatment with sirolimus, an mTOR inhibitor, induced remission in all three patients. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 29-33 31568401-10 2019 Disruption of PNO1 expression significantly reduced protein kinase B (AKT)/rapamycin (mTOR) signaling, indicating that this pathway may be involved in PNO1-mediated tumorigenic activity. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 86-90 31166253-8 2019 In addition, BNIP3 knockdown upregulated p-mTOR and p-p70s6k as well as decreased apoptosis, whereas rapamycin (which is an inhibitor of mTOR) reversed apoptosis. Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 137-141 31047942-0 2019 Preincubation With Everolimus and Sirolimus Reduces Organic Anion-Transporting Polypeptide (OATP)1B1- and 1B3-Mediated Transport Independently of mTOR Kinase Inhibition: Implication in Assessing OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 146-150 32274481-1 2019 PURPOSE: To investigate the expression of rapamycin target protein (mTOR) mRNA and transferrin receptor 1(Tfr1) mRNA in mucoepidermoid carcinoma of parotid gland and its relationship with prognosis. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 68-72 31579114-4 2019 The GC cells were subsequently transfected with siRNA against LINC01419 or Rapamycin (the inhibitor of the mTOR pathway), or both, in order to measure cell migration and invasion in vitro as well as tumor growth and metastasis in vivo. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 107-111 31723531-4 2019 This somatic mutation is, in turn, associated with the activation of the protein kinase B-mammalian target of the rapamycin (AKT-mTOR) pathway that drives various signaling cascades. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 129-133 31608069-7 2019 Use of allosteric panAkt inhibitor MK2206 and mTOR inhibitor rapamycin confirmed the role of Akt/mTOR signaling in autophagy inhibition by P. gingivalis in DCs. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 46-50 31299610-5 2019 Sirolimus as the most common mTOR (mammalian target of Rapamycin) inhibitor is able to effectively prevent allograft rejection. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 29-33 31483776-2 2019 The mammalian target of rapamycin (mTOR) inhibitor, rapamycin, is a treatment for advanced retinoblastoma. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 35-39 31296735-7 2019 Unexpectedly, rapamycin, a well-established inhibitor of mTOR, also strongly protected NK-A20-/- cells from death, and further studies revealed that A20 restricts mTOR activation in NK cells. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 57-61 31296735-7 2019 Unexpectedly, rapamycin, a well-established inhibitor of mTOR, also strongly protected NK-A20-/- cells from death, and further studies revealed that A20 restricts mTOR activation in NK cells. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 163-167 31649854-1 2019 Recently, considerable attention in the field of cancer therapy has been focused on the mammalian rapamycin target (mTOR), inhibition of which could result in autophagic cell death (ACD). Sirolimus 98-107 mechanistic target of rapamycin kinase Homo sapiens 116-120 31315433-10 2019 On the contrary, lentivirus-mediated overexpression of Rheb in macrophages increased oxidized LDL-induced lipid uptake and inflammation, and the stimulatory effect of Rheb was suppressed by the mTOR (mammalian target of rapamycin) inhibitor rapamycin or the PKA (protein kinase A) activator forskolin. Sirolimus 220-229 mechanistic target of rapamycin kinase Homo sapiens 194-198 31398711-3 2019 Several mTOR inhibitors, including sirolimus, temsirolimus and everolimus have been clinically developed. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 8-12 31546722-10 2019 On the other hand, inhibition of mTOR activation by rapamycin (an allosteric mTOR inhibitor) significantly attenuated neuronal death induced by HFD, showing reduction of HFD-induced increases of oxidative stress indicators and proinflammatory cytokines, and microglia activation. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 33-37 31546722-10 2019 On the other hand, inhibition of mTOR activation by rapamycin (an allosteric mTOR inhibitor) significantly attenuated neuronal death induced by HFD, showing reduction of HFD-induced increases of oxidative stress indicators and proinflammatory cytokines, and microglia activation. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 77-81 30672370-6 2019 Pre-treatment of spinal neurons with a PI3K inhibitor, LY294002 or mammalian target of rapamycin (mTOR) inhibitor, rapamycin blocked bpV activation of Akt and ribosomal protein S6 activity, respectively. Sirolimus 87-96 mechanistic target of rapamycin kinase Homo sapiens 98-102 31120172-4 2019 We showed that branching buds in the salivary glands were substantially decreased and phosphorylation of mTORC1 signalling pathway related proteins (mTOR, p70 ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E-binding protein 1) was inhibited by rapamycin (an mTOR inhibitor). Sirolimus 261-270 mechanistic target of rapamycin kinase Homo sapiens 105-109 31299610-5 2019 Sirolimus as the most common mTOR (mammalian target of Rapamycin) inhibitor is able to effectively prevent allograft rejection. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 35-64 31358596-4 2019 Rapamycin inhibits mTOR and is effective in preventing kidney transplant rejection, with the additional merits of reduced incidence of malignancies and viral infections. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 19-23 31021470-12 2019 Preconditioning with mTOR inhibitor rapamycin engendered not only a reduction in mTOR activation, but also a reactivation of autophagy in REDD1 knockdown-neurons upon OGD/R. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 21-25 31021470-12 2019 Preconditioning with mTOR inhibitor rapamycin engendered not only a reduction in mTOR activation, but also a reactivation of autophagy in REDD1 knockdown-neurons upon OGD/R. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 81-85 31404320-9 2019 Rapamycin and doxorubicin also reduced the phosphorylation levels of mTOR and p70S6K. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 69-73 31404320-12 2019 These results suggested that rapamycin could enhance the antitumor effects of doxorubicin on K562 cells by downregulating mTOR/p70S6K signaling. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 122-126 31102490-0 2019 Inhibition of mTOR by Rapamycin Aggravates Corneal Epithelial Stem Cell Deficiency by Upregulating Inflammatory Response. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 31102490-6 2019 Hence, our data reveal that the mTOR signaling is implicated in the control of the pro-inflammatory and anti-inflammatory balance in the cornea and that mTOR inhibition with rapamycin is detrimental to CESCs by accelerating inflammation-induced collateral damage to the cells. Sirolimus 174-183 mechanistic target of rapamycin kinase Homo sapiens 153-157 31524870-7 2019 From the proteolytic curve we saw that the proteolysis of mTOR by pronase was inhibited by the presence of rapamycin. Sirolimus 107-116 mechanistic target of rapamycin kinase Homo sapiens 58-62 31406198-8 2019 Furthermore, when combined with the inhibitors MK2206 and rapamycin to inhibit Akt and mTOR kinase activity, Pae-induced autophagy was increased. Sirolimus 58-67 mechanistic target of rapamycin kinase Homo sapiens 87-91 31408438-7 2019 Proteomic, immunophenotypic, and clinical response assessments were performed to quantify the effects of administration of the mTOR inhibitor, sirolimus. Sirolimus 143-152 mechanistic target of rapamycin kinase Homo sapiens 127-131 31404320-0 2019 Rapamycin enhanced the antitumor effects of doxorubicin in myelogenous leukemia K562 cells by downregulating the mTOR/p70S6K pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 113-117 31404320-5 2019 The aim of the present study was to investigate the effects of rapamycin and doxorubicin on K562 cell proliferation following the combination treatment, and further focus on confirming whether rapamycin enhanced the antitumor effects of doxorubicin by downregulating the mTOR/ribosomal protein S6 kinase (p70S6K) pathway. Sirolimus 193-202 mechanistic target of rapamycin kinase Homo sapiens 271-275 31173788-7 2019 Mechanistically, mTOR signaling, responsible for autophagy induction, was activated in vivo and in vitro, and targeting inhibition of mTOR with rapamycin protected SH-SY5Y cells from defective autophagy and excessive apoptosis, thereby enhancing neuronal survival. Sirolimus 144-153 mechanistic target of rapamycin kinase Homo sapiens 17-21 31173788-7 2019 Mechanistically, mTOR signaling, responsible for autophagy induction, was activated in vivo and in vitro, and targeting inhibition of mTOR with rapamycin protected SH-SY5Y cells from defective autophagy and excessive apoptosis, thereby enhancing neuronal survival. Sirolimus 144-153 mechanistic target of rapamycin kinase Homo sapiens 134-138 31150648-8 2019 However, rapamycin significantly inhibited mTOR, which can impact the anti-ischemic effect of crocin in vitro. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 43-47 31383843-7 2019 The intracellular calcium-dependent PKCalpha/mammalian target of the rapamycin (mTOR) signaling pathway triggered by cP1P regulated HIF1alpha translation via S6K1, which is critical for HIF1 activation. Sirolimus 69-78 mechanistic target of rapamycin kinase Homo sapiens 80-84 30549029-1 2019 Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, has significant potential for application in the treatment of urothelial carcinoma (URCa) of the bladder. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 13-42 30728467-9 2019 In HepG2 cells, rapamycin (a mTOR inhibitor) significantly reduced the OLZ-stimulated hepatocellular lipid contents and weakened the ability of Sim to lower lipids via a mechanism associated with the upregulation of SREBP1c-mediated de novo lipogenesis. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 29-33 31102854-2 2019 To combat in-stent restenosis, drug-eluting stents (DES) delivering mTOR inhibitors such as sirolimus or everolimus have become standard for coronary stenting. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 68-72 31066320-2 2019 This has resulted in calls for the use of the MTOR inhibitor rapamycin for the treatment of dementia in humans. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 46-50 30528864-1 2019 BACKGROUND: During the past decade, mTOR inhibitors (mTORi), everolimus and sirolimus, have been increasingly used after adult liver transplantation (LT). Sirolimus 76-85 mechanistic target of rapamycin kinase Homo sapiens 36-40 31173192-8 2019 Furthermore, co-treatment with MK-2206 (an Akt specific inhibitor) or rapamycin (an inhibitor of mTOR) enhanced T7 peptide-induced autophagy, whereas co-treatment with insulin (an activator of the Akt/mTOR signaling pathway) alleviated T7 peptide-induced autophagy, which suggested that the T7 peptide may induce autophagy activation via inhibition of the Akt/mTOR signaling pathway. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 97-101 30701530-9 2019 Knockdown of miR-30b reduced MMP and autophagy, elevated VC, and suppressed the presence of rapamycin (an inhibitor of the mTOR signaling pathway). Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 123-127 30549029-1 2019 Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, has significant potential for application in the treatment of urothelial carcinoma (URCa) of the bladder. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 44-48 31366686-9 2019 Treatment with sirolimus, an mTOR inhibitor, was initiated with the aim of inhibiting polyp growth. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 29-33 30710341-4 2019 Researchers report that rapamycin, a selective mTOR inhibitor, and immunosuppressive agent, has surprising immunostimulatory effects on inducing both quantitative and qualitative aspects of virus-specific memory CD8+ T-cells differentiation and homeostasis in a T-cell-intrinsic manner. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 47-51 31330912-7 2019 Additionally, the Akt (protein kinase B) inhibitor BML257 and the mTOR (mammalian target of rapamycin) inhibitor rapamycin contributed to the survival of astrocytes. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 66-70 30905858-1 2019 Rapamycin is an immunosuppressant that inhibits the mammalian or mechanistic target of rapamycin (mTOR) protein kinase and extends lifespan in organisms including mice. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 65-96 30905858-1 2019 Rapamycin is an immunosuppressant that inhibits the mammalian or mechanistic target of rapamycin (mTOR) protein kinase and extends lifespan in organisms including mice. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 98-102 31316104-7 2019 Rapamycin treatment rescued mitophagy, blocked the increase in MTOR and phosphorylated-MTOR, and increased the mitophagy-related gene expression in Gas6-depleted MII oocytes. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 63-67 31316104-7 2019 Rapamycin treatment rescued mitophagy, blocked the increase in MTOR and phosphorylated-MTOR, and increased the mitophagy-related gene expression in Gas6-depleted MII oocytes. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 87-91 31360296-8 2019 The protein kinase B/mammalian target of the rapamycin (Akt/mTOR) pathway which is involved in cardiac remodeling process was activated in response to norepinephrine and was mitigated by bucindolol. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 60-64 30445633-10 2019 Taken together, our study demonstrated that metformin suppressed the carcinogenesis of ESCC through inhibiting AMPK/mammalian target of the rapamycin (mTOR) signaling pathway, resulting in its chemopreventive effects on the carcinogenesis of ESCC. Sirolimus 140-149 mechanistic target of rapamycin kinase Homo sapiens 151-155 30959047-2 2019 We compared the effect of two synthetic mammalian mTOR blockers MC2141 and MC2183 with that of natural/plant-derived mTOR blocker rapamycin and mTOR activator resveratrol on cultured human ovarian granulosa cells. Sirolimus 130-139 mechanistic target of rapamycin kinase Homo sapiens 117-121 30959047-2 2019 We compared the effect of two synthetic mammalian mTOR blockers MC2141 and MC2183 with that of natural/plant-derived mTOR blocker rapamycin and mTOR activator resveratrol on cultured human ovarian granulosa cells. Sirolimus 130-139 mechanistic target of rapamycin kinase Homo sapiens 117-121 31338346-3 2019 Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been used as an immunosuppressant after organ transplantation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 13-42 30958627-5 2019 The expression of ERK1/2 and phosphatidylinositol 3 kinase/protein kinase B/mammalian targets of the rapamycin (PI3K/AKt/mTOR) signals and transferrin receptor (TfR/CD71) was detected with the methods of immunoblotting. Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 121-125 31025371-6 2019 Importantly, treatment of the mTOR inhibitor rapamycin blocked the neuroprotective effects of AO-2 on reducing LC3-II and cleaved Caspase-3 expression and cancelled AO-2-mediated neuronal survival. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 30-34 30499005-9 2019 mTOR inhibition with rapamycin effectively blocks the migration and proliferation of the RPE cells. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 0-4 30995105-6 2019 Interestingly, inhibition of mTOR with rapamycin did not alter HIF-1alpha or PDHK1 protein levels in LSFC fibroblasts. Sirolimus 39-48 mechanistic target of rapamycin kinase Homo sapiens 29-33 31338346-3 2019 Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been used as an immunosuppressant after organ transplantation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 44-48 31018220-10 2019 It was completely abolished by pretreatment of platelet-rich plasma with the mechanistic target of rapamycin (mTOR) inhibitors rapamycin or everolimus. Sirolimus 99-108 mechanistic target of rapamycin kinase Homo sapiens 110-114 30965356-10 2019 Rapamycin, an mTOR inhibitor, blocks IL-6Ralpha protein expression. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 31312368-7 2019 This migration promotion was alleviated by the specific mTOR inhibitor rapamycin, indicating that the GSK3/mTOR signaling pathway was involved in this process. Sirolimus 71-80 mechanistic target of rapamycin kinase Homo sapiens 56-60 31247000-10 2019 Rapamycin reduced phosphorylation of mTOR, and Ly-294,002 that of Akt. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 37-41 31312368-7 2019 This migration promotion was alleviated by the specific mTOR inhibitor rapamycin, indicating that the GSK3/mTOR signaling pathway was involved in this process. Sirolimus 71-80 mechanistic target of rapamycin kinase Homo sapiens 107-111 31247083-1 2019 Purpose: To analyze the activity of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinases/mechanistic target of rapamycin (PI3K/mTOR) pathways in benign and malignant conjunctival melanocytic proliferations and explore whether specific inhibitors can suppress growth of conjunctival melanoma (CJM) cells. Sirolimus 129-138 mechanistic target of rapamycin kinase Homo sapiens 145-149 31354297-3 2019 Rapamycin, an mTOR inhibitor, was reported to have anti-angiogenic and anti-lymphangiogenic properties. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 31354297-12 2019 Conclusion: In conclusion, rapamycin suppresses angiogenesis and lymphangiogenesis in melanoma by blocking the mTOR signal pathway and subsequently downregulating the expression of VEGF-A/VEGFR-2 and VEGF-C/VEGFR-3. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 111-115 31196153-8 2019 Rapamycin (a mTOR inhibitor, an autophagy activator) further down-regulated h/R-induced decrease of the phosphorylated PI3K, Akt and mTOR. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 13-17 31196153-8 2019 Rapamycin (a mTOR inhibitor, an autophagy activator) further down-regulated h/R-induced decrease of the phosphorylated PI3K, Akt and mTOR. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 133-137 31244838-12 2019 The mTOR inhibitor rapamycin restored pro-IL-1beta protein levels as well as LPS/ATP-induced IL-1beta release from serum starved cells. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 31236308-7 2019 Furthermore, studies demonstrated the efficacy of the mammalian target of rapamycin (mTOR) inhibitor sirolimus for these lymphatic diseases. Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 54-83 31236308-7 2019 Furthermore, studies demonstrated the efficacy of the mammalian target of rapamycin (mTOR) inhibitor sirolimus for these lymphatic diseases. Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 85-89 31120393-4 2019 Notably, targeting metabolism such as the mTOR by rapamycin, hexokinase by 2-deoxy-D-glucose, AMP-activated protein kinase by metformin, may be used to ameliorate autoimmune inflammation. Sirolimus 50-59 mechanistic target of rapamycin kinase Homo sapiens 42-46 31041622-13 2019 Rapamycin and NAC, which impact on the MTOR pathway, both reduced both pools of progerin without increasing prelamin A in HGPS cell nuclei. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 39-43 31125447-3 2019 Here, we further examined whether hypervascularization occurs in animal models of global and focal MCD with and without seizures, and whether it is sensitive to the mTOR blocker, rapamycin, that is approved for epilepsy treatment in tuberous sclerosis complex. Sirolimus 179-188 mechanistic target of rapamycin kinase Homo sapiens 165-169 30838516-2 2019 This study aims to describe the IGF pathway in ACC and to explore the response to the combined treatment with the IGF1R/IR inhibitor linsitinib, and mTOR inhibitors (sirolimus and everolimus) in in vitro models of ACC. Sirolimus 166-175 mechanistic target of rapamycin kinase Homo sapiens 149-153 31012209-1 2019 Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, is a potent immunosuppressant that is increasingly used in prevention and treatment of graft-vs-host disease (GVHD) in allogeneic hematopoietic stem cell transplant (HSCT) patients. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 13-42 31049797-5 2019 Rapamycin, an inhibitor of mTOR activity, can reverse the effect of DPSCs stimulated by IGF-1. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 30825612-9 2019 A higher compensatory increase in Akt phosphorylation after rapamycin treatment of LKB1-deficient cells than after rapamycin treatment of LKB1 wild-type cells is responsible for the synergistic effect of mTOR and PI3K inhibition. Sirolimus 60-69 mechanistic target of rapamycin kinase Homo sapiens 204-208 30825612-9 2019 A higher compensatory increase in Akt phosphorylation after rapamycin treatment of LKB1-deficient cells than after rapamycin treatment of LKB1 wild-type cells is responsible for the synergistic effect of mTOR and PI3K inhibition. Sirolimus 115-124 mechanistic target of rapamycin kinase Homo sapiens 204-208 31124053-1 2019 BACKGROUND: It has been 15 years since sirolimus, an mTOR inhibitor, received Food and Drug Administration approval to prevent acute rejection in kidney transplantation, and 8 years since its analog everolimus acquired the same status. Sirolimus 39-48 mechanistic target of rapamycin kinase Homo sapiens 53-57 31124053-4 2019 AIMS: The aims of this study were to describe our center"s experience with sirolimus and everolimus in managing rare pediatric conditions for which mTOR inhibitors have been reported as a therapeutic option, although without conclusive approval from regulatory agencies, and to evaluate safety and tolerability of the treatment at the prescribed doses. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 148-152 31130397-6 2019 Given the absence of worrisome feature, we ruled out surgery and decided to initiate treatment with Sirolimus, an mTOR inhibitor. Sirolimus 100-109 mechanistic target of rapamycin kinase Homo sapiens 114-118 30793789-0 2019 The effect of the mTOR inhibitor rapamycin on glucoCEST signal in a preclinical model of glioblastoma. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 18-22 30877063-9 2019 In contrast, sirolimus, temsirolimus, and everolimus are larger molecules (MW 1000) that bind to FKBP-12 to generate a complex that inhibits mTOR (mammalian target of rapamycin). Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 143-147 30877063-9 2019 In contrast, sirolimus, temsirolimus, and everolimus are larger molecules (MW 1000) that bind to FKBP-12 to generate a complex that inhibits mTOR (mammalian target of rapamycin). Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 149-178 31012209-1 2019 Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, is a potent immunosuppressant that is increasingly used in prevention and treatment of graft-vs-host disease (GVHD) in allogeneic hematopoietic stem cell transplant (HSCT) patients. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 44-48 30703503-0 2019 Functional Effects of Cuprizone-Induced Demyelination in the Presence of the mTOR-Inhibitor Rapamycin. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 77-81 31367538-2 2019 Preclinical studies showed promising synergistic effects when the mammalian target of rapamycin (mTOR) inhibitor sirolimus was added to pemetrexed. Sirolimus 113-122 mechanistic target of rapamycin kinase Homo sapiens 66-95 31367538-2 2019 Preclinical studies showed promising synergistic effects when the mammalian target of rapamycin (mTOR) inhibitor sirolimus was added to pemetrexed. Sirolimus 113-122 mechanistic target of rapamycin kinase Homo sapiens 97-101 31191530-7 2019 Our recent data suggest that Rapamycin treatment during TCP manufacture, conferring partial inhibition of mTOR, might improve its composition. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 106-110 31136303-4 2019 It is instead retarded by rapamycin, the potent inhibitor of the mTOR complex which governs many pathways relating to cellular metabolism. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 65-69 30703503-5 2019 Thus, in an effort to inhibit spontaneous remyelination, the mTOR inhibitor rapamycin has been administered during cuprizone diet. Sirolimus 76-85 mechanistic target of rapamycin kinase Homo sapiens 61-65 30989721-2 2019 Conversely, mechanistic target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) have been suggested to reduce recurrence rates and improve survival in this patient group. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 12-43 31091245-8 2019 Further studies indicated that pretreatment with the Akt inhibitor GSK690693 or the mTOR inhibitor rapamycin promoted Rk3-induced apoptosis and autophagy, demonstrating that the PI3K/Akt/mTOR pathway is related to Rk3-induced apoptosis and autophagy. Sirolimus 99-108 mechanistic target of rapamycin kinase Homo sapiens 84-88 31091245-8 2019 Further studies indicated that pretreatment with the Akt inhibitor GSK690693 or the mTOR inhibitor rapamycin promoted Rk3-induced apoptosis and autophagy, demonstrating that the PI3K/Akt/mTOR pathway is related to Rk3-induced apoptosis and autophagy. Sirolimus 99-108 mechanistic target of rapamycin kinase Homo sapiens 187-191 31010692-11 2019 However, a search of more effective way to target mTOR has generated a third generation inhibitor of mTOR, "Rapalink", that bivalently combines rapamycin with an ATP-binding inhibitor, which effectively abolishes the mTORC1 activity. Sirolimus 144-153 mechanistic target of rapamycin kinase Homo sapiens 50-54 31010692-11 2019 However, a search of more effective way to target mTOR has generated a third generation inhibitor of mTOR, "Rapalink", that bivalently combines rapamycin with an ATP-binding inhibitor, which effectively abolishes the mTORC1 activity. Sirolimus 144-153 mechanistic target of rapamycin kinase Homo sapiens 101-105 30989721-2 2019 Conversely, mechanistic target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) have been suggested to reduce recurrence rates and improve survival in this patient group. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 45-49 30814053-10 2019 By inhibiting mTOR signalling with metformin or rapamycin, a reduction of cell death and release of inflammatory mediators was observed. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 14-18 30270358-3 2019 As mTOR mediates the growth-promoting actions of PI3K, we hypothesized that the mTOR inhibitor sirolimus would slow pathological overgrowth. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 3-7 30724000-3 2019 Sirolimus is a mTOR pathway inhibitor, and has been tried successfully in the treatment of various vascular anomalies. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 15-19 30794430-7 2019 Moreover, inhibiting the mammalian target of rapamycin (mTOR) complex 1, an important downstream effector of PI3K-Akt, by short-term application of rapamycin attenuated the effects of M1 receptors on GluA1. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 56-60 30270358-3 2019 As mTOR mediates the growth-promoting actions of PI3K, we hypothesized that the mTOR inhibitor sirolimus would slow pathological overgrowth. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 80-84 30911930-0 2019 mTOR inhibitor sirolimus negatively impacts in vitro fertilization outcomes. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 0-4 31151763-7 2019 Treatment with the mTOR signaling pathway inhibitor, rapamycin, inhibited the phosphorylation of mTOR and AKT, decreased Snail and Vimentin protein levels, and increased VE-cad protein levels. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 19-23 31151763-7 2019 Treatment with the mTOR signaling pathway inhibitor, rapamycin, inhibited the phosphorylation of mTOR and AKT, decreased Snail and Vimentin protein levels, and increased VE-cad protein levels. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 97-101 31183237-2 2019 Sirolimus, an inhibitor of the mammalian target of rapamycin, is effective against vascular anomalies with few severe adverse drug reactions. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 31-60 30670777-6 2019 Rapamycin, a lactate transport blocker and metformin were used as modulators of the Akt-mTOR pathway and cell metabolism. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 88-92 30614215-3 2019 EBV utilizes the mammalian target of rapamycin (mTOR) pathway for tumor growth, and sirolimus, a mTOR inhibitor, has shown to result in a short-term response. Sirolimus 84-93 mechanistic target of rapamycin kinase Homo sapiens 17-46 30614215-3 2019 EBV utilizes the mammalian target of rapamycin (mTOR) pathway for tumor growth, and sirolimus, a mTOR inhibitor, has shown to result in a short-term response. Sirolimus 84-93 mechanistic target of rapamycin kinase Homo sapiens 97-101 30873702-9 2019 Meanwhile, repression of mTOR by rapamycin promoted autophagy and AIM2/caspase-1 activation. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 25-29 30976008-6 2019 MTOR inhibition by rapamycin equalizes cytokine production in CBMPhi and PBMPhi. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 0-4 30923227-11 2019 Furthermore, CB2R dysfunction significantly attenuated the cardiac protective effects of rapamycin both in vivo and in vitro Finally, we found that CB2R-mediated autophagy was induced by AMPK-mTOR-p70S6K signaling pathway. Sirolimus 89-98 mechanistic target of rapamycin kinase Homo sapiens 192-196 30860477-10 2019 In one approach, drugs can be targeted at known patient dysfunctional processes such as in the case of patients carrying autophagy-related genetic polymorphisms being treated with rapamycin, a drug that inhibits mTOR inhibitor and enhances autophagy. Sirolimus 180-189 mechanistic target of rapamycin kinase Homo sapiens 212-216 30552782-6 2019 Blockage of mTOR by rapamycin or inhibition of glutaminolysis abolished the discrepancy in tumorigenic capacity between SIRT4-depleted hepatoma cells and control cells. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 12-16 30747999-8 2019 Western blot for phosphorylated-S6 (pS6) and phosphorylated S6K confirmed that rapamycin inhibited the mTOR pathway, whereas curcumin only lowered pS6 expression at one phosphorylation site. Sirolimus 79-88 mechanistic target of rapamycin kinase Homo sapiens 103-107 30144378-10 2019 Consistently, the inhibition of mTOR by rapamycin also sensitized cells to cisplatin, and the effects of cisplatin plus rapamycin were identical to those obtained with cisplatin plus ADP. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 32-36 30317677-10 2019 Preconditioning with mTOR antagonist rapamycin engendered not only mTOR inhibition but also abrogated GAS5-mediated depression in cisplatin-evoked autophagy. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 21-25 30317677-10 2019 Preconditioning with mTOR antagonist rapamycin engendered not only mTOR inhibition but also abrogated GAS5-mediated depression in cisplatin-evoked autophagy. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 67-71 31019827-3 2019 Sirolimus, an inhibitor of the mammalian target of rapamycin, is a relatively new medical therapy for the treatment of vascular malformations. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 31-60 30242894-10 2019 Reversely, rapamycin or S3I-201 inhibited mTOR/STAT-3 activation. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 42-46 30972187-8 2019 Furthermore, combined inhibition of FGFR and mTOR pathways by BGJ398 and Rapamycin induced remarkable cell cycle arrest and apoptosis in OC cells. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 45-49 29752013-1 2019 BACKGROUND: Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor used after organ transplantation and to treat vascular malformations. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 27-56 31128031-0 2019 A study on the mechanism of rapamycin mediating the sensitivity of pancreatic cancer cells to cisplatin through PI3K/AKT/mTOR signaling pathway. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 121-125 31128031-1 2019 PURPOSE: To study the mechanism of rapamycin mediating the sensitivity of pancreatic cancer cells to cisplatin through phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling pathway in vitro. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 186-215 31128031-1 2019 PURPOSE: To study the mechanism of rapamycin mediating the sensitivity of pancreatic cancer cells to cisplatin through phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling pathway in vitro. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 217-221 31128031-7 2019 3: Rapamycin combined with cisplatin could inhibit the expressions of PI3K, AKT and phosphorylated mTOR (p-mTOR) in pancreatic cancer cells (p<0.05). Sirolimus 3-12 mechanistic target of rapamycin kinase Homo sapiens 99-103 31128031-7 2019 3: Rapamycin combined with cisplatin could inhibit the expressions of PI3K, AKT and phosphorylated mTOR (p-mTOR) in pancreatic cancer cells (p<0.05). Sirolimus 3-12 mechanistic target of rapamycin kinase Homo sapiens 107-111 31128031-8 2019 CONCLUSION: Rapamycin combined with cisplatin can alter the PI3K/AKT/mTOR signal transduction pathway which leads to markedly increased cell apoptosis rate, indicating that rapamycin can mediate the sensitivity of pancreatic cancer cells to cisplatin. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 69-73 31128031-8 2019 CONCLUSION: Rapamycin combined with cisplatin can alter the PI3K/AKT/mTOR signal transduction pathway which leads to markedly increased cell apoptosis rate, indicating that rapamycin can mediate the sensitivity of pancreatic cancer cells to cisplatin. Sirolimus 173-182 mechanistic target of rapamycin kinase Homo sapiens 69-73 30747221-11 2019 ER-positive breast cancer cells exhibiting low BAG-1 expression appeared to be more sensitive to treatment with the mTOR inhibitor rapamycin. Sirolimus 131-140 mechanistic target of rapamycin kinase Homo sapiens 116-120 30455224-1 2019 Tuberous sclerosis complex (TSC) is a rare disease that causes multisystem benign neoplasm, induced by dysregulation of the mammalian target of the rapamycin pathway (mTOR). Sirolimus 148-157 mechanistic target of rapamycin kinase Homo sapiens 167-171 29752013-1 2019 BACKGROUND: Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor used after organ transplantation and to treat vascular malformations. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 58-62 30420444-0 2019 Inhibition of mTOR Signaling and Clinical Activity of Rapamycin in Head and Neck Cancer in a Window of Opportunity Trial. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 14-18 30795552-4 2019 Mammalian (or mechanistic) target of rapamycin (mTOR) is a conserved serine/threonine kinase belonging to the phosphatidylinositol 3-kinase (PI3K)-related kinase family (PIKK) and resides in two distinct signalling complexes named mTORC1, involved in mRNA translation and protein synthesis and mTORC2 that controls cell survival and migration. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 48-52 30782662-7 2019 MLN0128 inhibited phosphorylation of mTOR complex 1 and 2 targets, while rapamycin only partially inhibited mTOR complex 1 targets. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 108-112 30791416-6 2019 Pharmacological activation of autophagy is typically achieved by blocking the kinase activity of mammalian target of rapamycin (mTOR) enzymatic complex 1 (mTORC1), removing its autophagy suppressor activity observed under physiological conditions; acting in this way, rapamycin provided the first proof of principle that pharmacological autophagy enhancement can induce neuroprotection through the facilitation of oligomers" clearance. Sirolimus 117-126 mechanistic target of rapamycin kinase Homo sapiens 128-132 30420444-1 2019 PURPOSE: We studied the impact of mTOR signaling inhibition with rapamycin in head and neck squamous cell carcinoma (HNSCC) in the neoadjuvant setting. Sirolimus 65-74 mechanistic target of rapamycin kinase Homo sapiens 34-38 30420444-13 2019 CONCLUSIONS: Rapamycin treatment was well tolerated, reduced mTOR signaling and tumor growth, and resulted in significant clinical responses despite the brief treatment duration, thus supporting the potential role of mTOR inhibitors in treatment regimens for HNSCC. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 61-65 30420444-13 2019 CONCLUSIONS: Rapamycin treatment was well tolerated, reduced mTOR signaling and tumor growth, and resulted in significant clinical responses despite the brief treatment duration, thus supporting the potential role of mTOR inhibitors in treatment regimens for HNSCC. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 217-221 30765891-7 2019 Cultured tissue slices were metabolically active and responsive to rapamycin, an mTOR inhibitor. Sirolimus 67-76 mechanistic target of rapamycin kinase Homo sapiens 81-85 30787878-2 2019 Inhibition of the mammalian target of rapamycin (mTOR) pathway by sirolimus, a drug approved and in clinical use to prevent transplant rejection, has shown promising effects in lupus animal models as well as in patients with both antiphospholipid syndrome and SLE. Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 18-47 30739121-2 2019 More recently, tapering of calcineurin inhibitor-based immunotherapies with concurrent administration of the mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus has been employed within pharmacological regimens designed to achieve better safety and efficacy for preservation of allograft kidney function. Sirolimus 157-166 mechanistic target of rapamycin kinase Homo sapiens 109-138 30739121-2 2019 More recently, tapering of calcineurin inhibitor-based immunotherapies with concurrent administration of the mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus has been employed within pharmacological regimens designed to achieve better safety and efficacy for preservation of allograft kidney function. Sirolimus 157-166 mechanistic target of rapamycin kinase Homo sapiens 140-144 30760308-0 2019 Efficacy and safety of mTOR inhibitors (rapamycin and its analogues) for tuberous sclerosis complex: a meta-analysis. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 23-27 30787878-2 2019 Inhibition of the mammalian target of rapamycin (mTOR) pathway by sirolimus, a drug approved and in clinical use to prevent transplant rejection, has shown promising effects in lupus animal models as well as in patients with both antiphospholipid syndrome and SLE. Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 49-53 30462552-5 2019 Inhibition of mTOR through siRNA-mediated depletion or treatment with chemical inhibitors rapamycin or torin 1 suppressed VCAM1 transcription, which translated to inhibition of VCAM-1 surface expression by HAECs and concomitant decreased adhesion of monocytes. Sirolimus 90-99 mechanistic target of rapamycin kinase Homo sapiens 14-18 30711941-2 2019 In this study, we investigated the combined effect of the autophagy inhibitor chloroquine and the mTOR inhibitor rapamycin on MG63 osteosarcoma cells. Sirolimus 113-122 mechanistic target of rapamycin kinase Homo sapiens 98-102 30711941-4 2019 Effects of chloroquine and/or rapamycin on the mTOR pathway components, autophagy, and apoptosis were investigated by western blot, flow cytometry, and fluorescence microscopy using immunocytochemical staining of LC3 and Annexin V-FITC/propidium iodide. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 47-51 30711941-6 2019 Rapamycin promoted autophagy by blocking the mTOR pathway, and chloroquine enhanced apoptosis by blocking autophagy. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 45-49 31056947-4 2019 On the other hand, mTOR inhibitors, as rapamycin and/or its derivatives, restore corticosteroid sensitivity in peripheral blood mononuclear cells from chronic obstructive pulmonary disease (COPD) patients, and overexpression of mTOR suppresses cigarette smoke-induced inflammation and emphysema, suggesting that induction of mTOR expression/activity might be useful to treat COPD. Sirolimus 39-48 mechanistic target of rapamycin kinase Homo sapiens 19-23 30548896-3 2019 Sirolimus, an inhibitor of mammalian target of rapamycin, is used for immunosuppression in kidney transplantation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-56 31056947-4 2019 On the other hand, mTOR inhibitors, as rapamycin and/or its derivatives, restore corticosteroid sensitivity in peripheral blood mononuclear cells from chronic obstructive pulmonary disease (COPD) patients, and overexpression of mTOR suppresses cigarette smoke-induced inflammation and emphysema, suggesting that induction of mTOR expression/activity might be useful to treat COPD. Sirolimus 39-48 mechanistic target of rapamycin kinase Homo sapiens 228-232 31056947-4 2019 On the other hand, mTOR inhibitors, as rapamycin and/or its derivatives, restore corticosteroid sensitivity in peripheral blood mononuclear cells from chronic obstructive pulmonary disease (COPD) patients, and overexpression of mTOR suppresses cigarette smoke-induced inflammation and emphysema, suggesting that induction of mTOR expression/activity might be useful to treat COPD. Sirolimus 39-48 mechanistic target of rapamycin kinase Homo sapiens 228-232 30489210-3 2019 Animal studies investigating the effect of rapamycin on mTOR inhibition following cerebral ischemia have shown conflicting results. Sirolimus 43-52 mechanistic target of rapamycin kinase Homo sapiens 56-60 30682771-6 2019 Rapalogs, such as sirolimus and everolimus, partially inhibit mTOR complex 1 (mTORC1) and exhibit anti-cancer activity in vitro and in vivo in BTC. Sirolimus 18-27 mechanistic target of rapamycin kinase Homo sapiens 62-66 30615938-0 2019 Rapamycin - mTOR + BRAF = ? Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 12-16 30569107-8 2019 The antioxidant N-acetylcysteine, the phosphoinositide 3-kinase (PI3K)/AKT inhibitor LY294002 and the mTOR inhibitor rapamycin ameliorated the effects of high glucose. Sirolimus 117-126 mechanistic target of rapamycin kinase Homo sapiens 102-106 29405800-2 2019 Recently, pharmacologic inhibition of the mTOR pathway by sirolimus was reported as a safe and efficacious treatment option for lymphatic malformations (also known as lymphangiomas). Sirolimus 58-67 mechanistic target of rapamycin kinase Homo sapiens 42-46 30621732-17 2019 Rapamycin may be an effective treatment for non-syndromic ASD in adolescent and adult patients who present impairments in the mTOR signaling pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 126-130 30847392-5 2019 Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor that inhibits the pathway downstream of PIK3CA. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 15-44 30847392-5 2019 Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor that inhibits the pathway downstream of PIK3CA. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 46-50 30581017-6 2019 Pharmacological intervention with the mTOR regulator rapamycin suppressed these defects. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 38-42 30858935-2 2019 Sirolimus inhibits mammalian target of rapamycin (mTOR) and its administration in past studies was hopeful in treatment of patients with LAM. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 19-48 30414939-13 2019 In addition, ACSL4 inhibition and chemotherapeutic treatment combined with rapamycin-induced mTOR inhibition synergically inhibited proliferation and reduced ABCG2 expression in cells overexpressing ACSL4. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 93-97 30858935-2 2019 Sirolimus inhibits mammalian target of rapamycin (mTOR) and its administration in past studies was hopeful in treatment of patients with LAM. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 50-54 30651769-0 2019 The combination of NVP-BEZ235 and rapamycin regulates nasopharyngeal carcinoma cell viability and apoptosis via the PI3K/AKT/mTOR pathway. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 125-129 30387804-8 2019 Treatment of MDAH-2774 cells with the mTOR inhibitors resulted in the significant upregulation of DEPTOR mRNA, whereas treatment with rapamycin and BEZ-235 (100 nM) resulted in downregulation of the mTOR protein expression after 48 h of treatment. Sirolimus 134-143 mechanistic target of rapamycin kinase Homo sapiens 199-203 30542717-5 2019 We demonstrated that rapamycin, an FDA-approved mammalian target of rapamycin (mTOR) inhibitor, enhanced the effects of endocrine therapy with tamoxifen, and the concentration of tamoxifen required for ER+ breast cancer cell growth inhibition was substantially reduced. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 48-77 30334673-7 2019 One such therapy already in use in transplant medicine is the mTOR inhibitor rapamycin. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 62-66 30542717-5 2019 We demonstrated that rapamycin, an FDA-approved mammalian target of rapamycin (mTOR) inhibitor, enhanced the effects of endocrine therapy with tamoxifen, and the concentration of tamoxifen required for ER+ breast cancer cell growth inhibition was substantially reduced. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 79-83 30888659-6 2019 Resveratrol, rapamycin, metformin and aspirin, showing effectiveness in model organism life- and healthspan extension mainly target the master regulators of aging such as mTOR, FOXO and PGC1alpha, affecting autophagy, inflammation and oxidative stress. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 171-175 30619313-0 2018 Selective Effects of mTOR Inhibitor Sirolimus on Naive and CMV-Specific T Cells Extending Its Applicable Range Beyond Immunosuppression. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 21-25 30619313-2 2018 However, recent clinical observations indicate that mammalian target of rapamycin (mTOR) inhibition with sirolimus may improve the outcome of CMV complications. Sirolimus 105-114 mechanistic target of rapamycin kinase Homo sapiens 52-81 30619313-2 2018 However, recent clinical observations indicate that mammalian target of rapamycin (mTOR) inhibition with sirolimus may improve the outcome of CMV complications. Sirolimus 105-114 mechanistic target of rapamycin kinase Homo sapiens 83-87 30145837-5 2018 Besides, the regulatory relationships between Sox2ot and miR-211, miR-211 and MCL-1, as well as between MCL-1 and the protein kinase B (Akt)/mammalian target of the rapamycin (mTOR)/p70 ribosomal S6 protein kinase (p70S6K) signaling pathway were explored. Sirolimus 165-174 mechanistic target of rapamycin kinase Homo sapiens 176-180 30138677-8 2018 Treatment with rapamycin ameliorated the lymphoproliferative immunodeficiency caused by hyperactivation of mTOR. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 107-111 30198771-7 2018 Blocking mTOR pathway with rapamycin eliminated such neuroprotective effects of BCAAs. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 9-13 30297200-12 2018 Other agents such as tyrosine kinase inhibitors (imatinib and nilotinib) and mTOR inhibitors (sirolimus) may also cause eyelid edema. Sirolimus 94-103 mechanistic target of rapamycin kinase Homo sapiens 77-81 30442335-3 2018 Rapamycin, a macrolide antibiotic and mTOR inhibitor, has recently also been implicated in telomerase inhibition and telomere attrition, although the mechanisms remain poorly understood. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 38-42 29663284-10 2018 Use of the mTOR inhibitor rapamycin blunts the effects of FLX on body weight and on functional and structural plasticity of POMC neurons. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 11-15 30442335-4 2018 Using breast cancer cells (MCF-7 and MDA-MB-231) wherein telomerase activity and mTOR pathway are concurrently overexpressed, this study sought to unravel novel mechanisms by which rapamycin may affect these pathways. Sirolimus 181-190 mechanistic target of rapamycin kinase Homo sapiens 81-85 30442335-7 2018 While long term treatment with a clinically relevant dose of rapamycin resulted in compromised population doubling capacity and mTOR pathway inhibition, there was no effect on telomere functionality and telomerase activity as evidenced by our assessments of hTERT protein levels, in vitro telomerase activity, telomere length and telomere FISH analyses. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 128-132 30393233-8 2018 The WB results showed that the expression levels of Beclin-1 and LC3-II/LC3-I were significantly elevated in NB cells treated with Rapamycin, while the expression levels of P62, mTOR, and p-mTOR proteins were significantly reduced compared with the control cells (P<0.05). Sirolimus 131-140 mechanistic target of rapamycin kinase Homo sapiens 178-182 30060978-2 2018 Recently, an intravitreal formulation of sirolimus, an immunosuppressant that inhibits the mammalian target of rapamycin, a key regulator of cell growth in the immune system, was developed. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 91-120 29964224-8 2018 RESULTS: mTOR pathway inhibitor rapamycin decreased the level of P-p70 S6K reduced by ALA-PDT. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 9-13 30393233-8 2018 The WB results showed that the expression levels of Beclin-1 and LC3-II/LC3-I were significantly elevated in NB cells treated with Rapamycin, while the expression levels of P62, mTOR, and p-mTOR proteins were significantly reduced compared with the control cells (P<0.05). Sirolimus 131-140 mechanistic target of rapamycin kinase Homo sapiens 190-194 29380900-3 2018 In this study, we report a novel dendrimer conjugate modified to deliver the mammalian target of rapamycin (mTOR) inhibitor, rapamycin. Sirolimus 97-106 mechanistic target of rapamycin kinase Homo sapiens 108-112 30357890-1 2018 Rapamycin is an mTOR allosteric inhibitor with multiple functions such as immunosuppressive, anticancer, and lifespan prolonging activities. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 16-20 30422993-2 2018 Sirolimus, an inhibitor of mammalian target of rapamycin (mTOR), was effective in improving clinical outcomes in patients with severe H1N1 infection; however, the mechanisms by which it attenuates acute lung injury have not been elucidated. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-56 30422993-2 2018 Sirolimus, an inhibitor of mammalian target of rapamycin (mTOR), was effective in improving clinical outcomes in patients with severe H1N1 infection; however, the mechanisms by which it attenuates acute lung injury have not been elucidated. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 58-62 30422993-10 2018 These results demonstrated that combined treatment with sirolimus and oseltamivir attenuates pH1N1-induced severe lung injury, which is correlated with suppressed mTOR-NLRP3-IL-1beta axis and reduced viral titer. Sirolimus 56-65 mechanistic target of rapamycin kinase Homo sapiens 163-167 30005812-1 2018 OBJECTIVE: To evaluate the safety of mTOR inhibitors (sirolimus or everolimus) in infants and very young children with tuberous sclerosis complex (TSC) under two years of age. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 37-41 29449635-7 2018 The mTOR inhibitor rapamycin rescued the deficits in differentiation, synaptic dysfunction, and hypoexcitability of TSC2 mutant hiPSC-PCs in vitro. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 30499059-6 2018 The changes of phosphorylation of Akt and mammalian target of rapamycin (mTOR) signaling pathway after rapamycin treatment were detected by flow cytometry and real-time PCR. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 73-77 30499059-13 2018 Rapamycin inhibited the activated Akt-mTOR signaling pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 38-42 30499059-15 2018 Treatment with the mTOR inhibitor rapamycin improved patient outcomes. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 19-23 30220530-0 2018 The mTOR-inhibitor Sirolimus decreases the cyclosporine-induced expression of the oncogene ATF3 in human keratinocytes. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 30220530-2 2018 Randomized studies of kidney-transplanted patients indicate a significant lower susceptibility for cSCC among patients receiving the mTOR-inhibitor Sirolimus, compared to patients without mTOR-regimen. Sirolimus 148-157 mechanistic target of rapamycin kinase Homo sapiens 133-137 29772587-5 2018 In accordance with rapamycin, the activation of the mammalian target of rapamycin and its downstream target, ribosomal protein S6 kinase 1, was inhibited by cardamonin, while pyrrolidine dithiocarbamate substantially blocked nuclear factor-kappaB activation and mildly inhibited the phosphorylation of the mammalian target of rapamycin and ribosomal protein S6 kinase 1. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 52-81 29772587-7 2018 In cells pretreated with rapamycin, the inhibitory effects of cardamonin were completely suppressed with regards to the phosphorylation of the mammalian target of rapamycin, ribosomal protein S6 kinase 1, TNF-alpha, and interleukin-6, and nuclear factor-kappaB p65 protein expression was decreased. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 143-172 30510618-3 2018 Since the discovery of rapamycin (or sirolimus), more than four decades ago, advances in our understanding of how mTOR participates in renal physiological and pathological mechanisms have grown exponentially, due to both preclinical studies in animal models with genetic modification of some mTOR components as well as due to evidence coming from the clinical experience. Sirolimus 23-32 mechanistic target of rapamycin kinase Homo sapiens 114-118 30373605-3 2018 Recent preclinical and clinical data demonstrated that sirolimus could offset the progression of vascular malformations and significantly improve quality of life of patients through inhibition of the Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian Target of Rapamycin (mTOR) pathway. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 241-270 30373605-3 2018 Recent preclinical and clinical data demonstrated that sirolimus could offset the progression of vascular malformations and significantly improve quality of life of patients through inhibition of the Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian Target of Rapamycin (mTOR) pathway. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 272-276 30713663-12 2019 The addition of rapamycin, the mTOR inhibitor, activated the autophagic pathway that accelerated the removal of damaged proteins. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 31-35 30564080-1 2018 Everolimus (EVR), as a rapamycin analog, is a selective inhibitor of the mammalian target of rapamycin (mTOR) kinase and its associated signaling pathway. Sirolimus 23-32 mechanistic target of rapamycin kinase Homo sapiens 73-102 30564080-1 2018 Everolimus (EVR), as a rapamycin analog, is a selective inhibitor of the mammalian target of rapamycin (mTOR) kinase and its associated signaling pathway. Sirolimus 23-32 mechanistic target of rapamycin kinase Homo sapiens 104-108 30510618-3 2018 Since the discovery of rapamycin (or sirolimus), more than four decades ago, advances in our understanding of how mTOR participates in renal physiological and pathological mechanisms have grown exponentially, due to both preclinical studies in animal models with genetic modification of some mTOR components as well as due to evidence coming from the clinical experience. Sirolimus 23-32 mechanistic target of rapamycin kinase Homo sapiens 292-296 30510618-3 2018 Since the discovery of rapamycin (or sirolimus), more than four decades ago, advances in our understanding of how mTOR participates in renal physiological and pathological mechanisms have grown exponentially, due to both preclinical studies in animal models with genetic modification of some mTOR components as well as due to evidence coming from the clinical experience. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 114-118 30337735-10 2018 Moreover, the knock down of either Ulk1 or LC3 decreased the ST-caused apoptosis.Interestingly, we observed that rapamycin, a specific inhibitor of mTOR (mammalian target of rapamycin) and an inducer of autophagy, also showed to inhibit cell viability and increased the cleavage of PARP-1 in the ST-treated cells, suggesting that autophagy was likely to play a dual role in the regulation of the ST-induced apoptosis. Sirolimus 113-122 mechanistic target of rapamycin kinase Homo sapiens 148-152 30337735-10 2018 Moreover, the knock down of either Ulk1 or LC3 decreased the ST-caused apoptosis.Interestingly, we observed that rapamycin, a specific inhibitor of mTOR (mammalian target of rapamycin) and an inducer of autophagy, also showed to inhibit cell viability and increased the cleavage of PARP-1 in the ST-treated cells, suggesting that autophagy was likely to play a dual role in the regulation of the ST-induced apoptosis. Sirolimus 113-122 mechanistic target of rapamycin kinase Homo sapiens 154-183 30416863-12 2018 Levels of p-mTOR (Ser2448) and p-p70S6K (Thr389) increased in URI-overexpressing cells treated with the mTOR inhibitor rapamycin but decreased in URI-silenced cells. Sirolimus 119-128 mechanistic target of rapamycin kinase Homo sapiens 12-16 30324134-7 2018 Furthermore, the muscle contractions were recovered by single treatments and cotreatment with rapamycin (a mechanistic target of rapamycin inhibitor) and bosutinib (an Src/c-Abl inhibitor). Sirolimus 94-103 mechanistic target of rapamycin kinase Homo sapiens 107-138 30326670-2 2018 mTOR functions in two distinct complexes-mTORC1 is sensitive to rapamycin, while, mTORC2 is insensitive to this drug. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 0-4 30416863-12 2018 Levels of p-mTOR (Ser2448) and p-p70S6K (Thr389) increased in URI-overexpressing cells treated with the mTOR inhibitor rapamycin but decreased in URI-silenced cells. Sirolimus 119-128 mechanistic target of rapamycin kinase Homo sapiens 104-108 30285764-15 2018 CONCLUSIONS: Menin is involved in regulatory mechanism between the two mTOR complexes, and its reduced expression is accompanied with increased mTORC2-Akt signaling, which consequently impairs anti-migratory effect of rapamycin. Sirolimus 218-227 mechanistic target of rapamycin kinase Homo sapiens 71-75 29758325-9 2018 However, these effects were reversed by AICAR (an agonist of adenosine monophosphate [AMP]-activated protein kinase [AMPK]) and rapamycin (an inhibitor of mammalian target of rapamycin [mTOR]). Sirolimus 128-137 mechanistic target of rapamycin kinase Homo sapiens 186-190 29758325-9 2018 However, these effects were reversed by AICAR (an agonist of adenosine monophosphate [AMP]-activated protein kinase [AMPK]) and rapamycin (an inhibitor of mammalian target of rapamycin [mTOR]). Sirolimus 128-137 mechanistic target of rapamycin kinase Homo sapiens 155-184 30223538-2 2018 Constitutive activation of the phosphatidylinositol-3-kinase-Akt-mechanistic target of rapamycin (PI3K-Akt-mTOR) pathway is present in AML cells, and this pathway integrates signaling from several upstream receptors/mediators. Sirolimus 87-96 mechanistic target of rapamycin kinase Homo sapiens 107-111 29744857-8 2018 Similarly, inhibition of mTOR with Rapamycin totally abolished the 10 microM NaHS-induced stimulation of PMECs proliferation and alteration of proliferative genes expression, with no influence on PI3 K/Akt signaling pathway. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 25-29 29627129-7 2018 Rapamycin, a PIK3/AKT/mTOR pathway inhibitor, demonstrated its efficiency for some forms of PROS. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 22-26 30208576-6 2018 Inhibition of PI3K/AKT/mTOR signaling pathway in the DU-145 cells by employing inhibitor LY294002 (10 muM) or rapamycin (20 nM) effectively attenuated AAP-H-induced phosphorylation of AKT and mTOR. Sirolimus 110-119 mechanistic target of rapamycin kinase Homo sapiens 23-27 30258985-2 2018 Although rapamycin inhibits the two canonical mTOR complexes, mTORC1 and mTORC2, it often shows minimal benefit as an anticancer drug. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 46-50 30258985-3 2018 This is caused by rapamycin resistance of many different tumors, and we show that a third mTOR complex, mTORC3, contributes to this resistance. Sirolimus 18-27 mechanistic target of rapamycin kinase Homo sapiens 90-94 30208576-6 2018 Inhibition of PI3K/AKT/mTOR signaling pathway in the DU-145 cells by employing inhibitor LY294002 (10 muM) or rapamycin (20 nM) effectively attenuated AAP-H-induced phosphorylation of AKT and mTOR. Sirolimus 110-119 mechanistic target of rapamycin kinase Homo sapiens 192-196 30109759-3 2018 Rapamycin, also known as sirolimus, selectively inhibits mammalian target of rapamycin, a regulatory kinase responsible for multiple signal transduction pathways. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 57-86 29203371-9 2018 The expression of Sema3A, and mTOR signaling were up-regulated in HaCaT cells incubated with HG or rSema3A, and this could be attenuated by rapamycin. Sirolimus 140-149 mechanistic target of rapamycin kinase Homo sapiens 30-34 29979258-6 2018 Sirolimus, an mTor inhibitor, has benefited patients with primary autoimmune cytopenias, possibly by stimulating T regulatory cells, and may also have efficacy for SLE-associated cytopenias. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 30181250-4 2018 The Akt/mammalian target of sirolimus (mTOR) pathway is inhibited by both bacterial species in vitro, indicating that several regulatory pathways are involved in the distinct intracellular lipid outcomes associated with each bacterial species. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 39-43 30066399-5 2018 Furthermore, preincubation of ex-vivo-expanded DN Tregs with a mechanistic target of rapamycin (mTOR) inhibitor rapamycin enhanced their immune regulatory function further. Sirolimus 85-94 mechanistic target of rapamycin kinase Homo sapiens 96-100 30109759-3 2018 Rapamycin, also known as sirolimus, selectively inhibits mammalian target of rapamycin, a regulatory kinase responsible for multiple signal transduction pathways. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 57-86 31949841-2 2018 As a natural mTOR inhibitor, rapamycin has been demonstrated to regulate various cellular biological behaviors of cancer cells, including growth inhibition and induction of apoptosis in multiple types of malignant tumors. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 13-17 30170968-5 2018 In vivo modulation of mTOR and autophagy was achieved by using AZD8055, rapamycin and 3-methyladenine. Sirolimus 72-81 mechanistic target of rapamycin kinase Homo sapiens 22-26 29964122-2 2018 Herein, inhalable multi-compartmental nanocomposites with the capability for both localized and modulated release of the hydrophobic mTOR inhibitor, rapamycin (RAP) and the hydrophilic herbal drug, berberine (BER) have been developed for lung cancer therapy. Sirolimus 149-158 mechanistic target of rapamycin kinase Homo sapiens 133-137 30347925-11 2018 Furthermore, the inhibition of PI3K/Akt by LY294002 or that of mTOR by rapamycin augmented LCA-induced autophagy. Sirolimus 71-80 mechanistic target of rapamycin kinase Homo sapiens 63-67 29748632-8 2018 In addition, we found that inhibition of Akt/mTOR pathway by rapamycin blocks the changes in 5-HT2AR signaling pattern and the supersensitivity to schizophrenia-like effects induced by chronic THC. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 45-49 30015406-1 2018 The mTOR inhibitor rapamycin is used systemically for the treatment of vascular lesions. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 30058583-9 2018 Results: The beneficial effects of rapamycin on neuropathic pain were attributed to a reduction in mammalian target of rapamycin sensitive complex 1 (mTORC1)-positive cells (70.80 +- 2.41 vs. 112.30 +- 5.66, F = 34.36, P < 0.01) and mTORC1 activity in the mouse spinal cord. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 99-128 30154572-7 2018 We inhibited mTOR by treating MCF7 cells with rapamycin and observed that the expression of NMT1 increased with rapamycin treatment over the period of time with a concomitant decrease in mTOR phosphorylation. Sirolimus 46-55 mechanistic target of rapamycin kinase Homo sapiens 13-17 30154572-7 2018 We inhibited mTOR by treating MCF7 cells with rapamycin and observed that the expression of NMT1 increased with rapamycin treatment over the period of time with a concomitant decrease in mTOR phosphorylation. Sirolimus 112-121 mechanistic target of rapamycin kinase Homo sapiens 13-17 30135653-1 2018 Rapamycin (sirolimus) is a mTOR kinase inhibitor and is widely used as an immunosuppressive drug to prevent graft rejection in organ transplantation currently. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 30135653-1 2018 Rapamycin (sirolimus) is a mTOR kinase inhibitor and is widely used as an immunosuppressive drug to prevent graft rejection in organ transplantation currently. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 27-31 30135653-4 2018 Using lentivirus-mediated small hairpin RNA (shRNA) we demonstrated that knockdown of mTOR, Raptor, or Rictor mimicked the effect of rapamycin treatment. Sirolimus 133-142 mechanistic target of rapamycin kinase Homo sapiens 86-90 30135653-5 2018 Mechanistically, inhibition of mTOR activity with rapamycin resulted in a hyperactive PI3K-Akt pathway, whereas this activation inhibited the expression of CTGF in HPCs. Sirolimus 50-59 mechanistic target of rapamycin kinase Homo sapiens 31-35 30015070-4 2018 Enzyme inhibition assay was performed for compound 19 against mTOR (IC50 = 0.64 muM) and VEGFR-2 (IC50 = 1.97 muM) to show high potency in comparison to rapamycin (IC50 = 0.43 muM) and sorafenib (IC50 = 0.3 muM) as references, respectively. Sirolimus 153-162 mechanistic target of rapamycin kinase Homo sapiens 62-66 29924669-0 2018 Treatment of Lymphatic Malformations with the mTOR Inhibitor Sirolimus: A Systematic Review. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 46-50 30219159-13 2018 Furthermore, in vitro studies revealed that the inhibitory effect of rapamycin on the angiogenic ability of HUVECs and its significant inhibitory effects on the protein level of HIF-1alpha and the phosphorylation of proteins involved in the mTORC1 pathway, including mTOR, raptor and p70S6K (P < 0.05), were enhanced by cotreatment with SRT1720 and rapamycin (P < 0.05). Sirolimus 69-78 mechanistic target of rapamycin kinase Homo sapiens 241-245 29857052-4 2018 Pre-senescent HUVECs were prolonged treated with low dose rapamycin (1 nM), an MTOR inhibitor. Sirolimus 58-67 mechanistic target of rapamycin kinase Homo sapiens 79-83 29857052-5 2018 Rapamycin treatment down-regulated the phosphorylated MTOR, RPS6 and 4EBP1 expressions, which confirmed MTORC1 suppression. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 54-58 29948021-1 2018 BACKGROUND: Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 27-56 29948021-1 2018 BACKGROUND: Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 58-62 29948021-2 2018 Metformin may potentiate mTOR inhibition by sirolimus while mitigating its adverse effects. Sirolimus 44-53 mechanistic target of rapamycin kinase Homo sapiens 25-29 29676052-1 2018 We evaluated the neuroprotective role of rapamycin, a mammalian target of rapamycin (mTOR) kinase inhibitor, in cerebral ischaemia and locomotor function in a mouse model of subarachnoid haemorrhage (SAH). Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 54-83 29676052-1 2018 We evaluated the neuroprotective role of rapamycin, a mammalian target of rapamycin (mTOR) kinase inhibitor, in cerebral ischaemia and locomotor function in a mouse model of subarachnoid haemorrhage (SAH). Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 85-89 30037344-1 2018 BACKGROUND: Previous studies in various rodent epilepsy models have suggested that mammalian target of rapamycin (mTOR) inhibition with rapamycin has anti-epileptogenic potential. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 114-118 29929111-1 2018 PURPOSE: Tuberous sclerosis (TSC) is an autosomal dominant inherited disease caused by mutations in the TSC1 or TSC2 gene and results in the over-activation of the mammalian target of the rapamycin (mTOR) signaling pathway. Sirolimus 188-197 mechanistic target of rapamycin kinase Homo sapiens 199-203 29929111-2 2018 Rapamycin, an mTOR inhibitor, is clinically used to treat hamartomatous lesionsas in TSC and its effect on controlling epilepsy is also reported in many studies. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 30037344-8 2018 RESULTS: Rapamycin, but not curcumin, suppressed mTOR activation in cultured astrocytes. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 49-53 30057537-3 2018 Case Report: We treated 3 consecutive infants aged less than 12 months with sirolimus, an oral mTOR inhibitor. Sirolimus 76-85 mechanistic target of rapamycin kinase Homo sapiens 95-99 29668485-2 2018 Conventional chemotherapy has little activity in this disease, but case reports are available on the activity of mammalian target of rapamycin inhibitors (e.g. sirolimus and temsirolimus). Sirolimus 160-169 mechanistic target of rapamycin kinase Homo sapiens 113-142 29668485-11 2018 This case confirms the activity of mammalian target of rapamycin inhibitors in PEComa and strengthens the importance of pharmacokinetic drug blood levels monitoring in patients treated with sirolimus. Sirolimus 190-199 mechanistic target of rapamycin kinase Homo sapiens 35-64 29889583-1 2018 OBJECTIVES: Constitutive signaling through the phosphatidylinositol-3-kinase-Akt-mammalian target of rapamycin (PI3K-Akt-mTOR) pathway is present in acute myeloid leukemia (AML) cells. Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 121-125 29945674-5 2018 Sirolimus directly inhibits the mTOR pathway, thereby inhibiting cell proliferation and angio/lymphangiogenesis. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 32-36 30317760-9 2018 Rapamycin alleviated lipid deposition caused by oleic acid and palmitic acid and inhibited their induction of increased expression of mTOR, S6K1, and SREBP-1c. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 134-138 29727731-2 2018 Although it has been shown that rapamycin (a specific inhibitor of mammalian target of rapamycin) can reduce astrocyte reactivation in the early stage of TBI, its effect on glial scar formation has not been characterized in TBI and other acute brain injury models. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 67-96 29481864-12 2018 DEPDC5/NPRL3 KD effects on morphology and functional mTOR activation were reversed by rapamycin. Sirolimus 86-95 mechanistic target of rapamycin kinase Homo sapiens 53-57 29447340-10 2018 In addition, silencing DDIT4 caused up-regulated p-mTOR and p-p70s6k and reduced apoptosis, whereas rapamycin, an inhibitor of mTOR, reversed the result of apoptosis. Sirolimus 100-109 mechanistic target of rapamycin kinase Homo sapiens 127-131 29757021-7 2018 Other studies report that Advagraf -treated patients receiving a mTOR-inhibitor agent (sirolimus or everolimus) instead of MMF: this was associated with good allograft outcome, and might also prevent late-onset cytomegalovirus infection. Sirolimus 87-96 mechanistic target of rapamycin kinase Homo sapiens 65-69 29483712-8 2018 Importantly, mTOR inhibition with rapamycin inhibited anti-huCD69-induced mobilization of hematopoietic stem and progenitor cells (HSPCs). Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 13-17 29885659-5 2018 Current immunomodulators include various immunosuppressants and biologics but mammalian target of rapamycin (mTOR) inhibitors (such as sirolimus and everolimus) may also be contenders for this role. Sirolimus 135-144 mechanistic target of rapamycin kinase Homo sapiens 78-107 29885659-5 2018 Current immunomodulators include various immunosuppressants and biologics but mammalian target of rapamycin (mTOR) inhibitors (such as sirolimus and everolimus) may also be contenders for this role. Sirolimus 135-144 mechanistic target of rapamycin kinase Homo sapiens 109-113 29226570-2 2018 Elective conversion to inhibitors of the mammalian target of rapamycin (mTOR, eg, sirolimus) pathway might avoid long-term CNI renal damage and improve outcomes. Sirolimus 82-91 mechanistic target of rapamycin kinase Homo sapiens 41-70 29226570-2 2018 Elective conversion to inhibitors of the mammalian target of rapamycin (mTOR, eg, sirolimus) pathway might avoid long-term CNI renal damage and improve outcomes. Sirolimus 82-91 mechanistic target of rapamycin kinase Homo sapiens 72-76 29175009-1 2018 BACKGROUND: The mammalian targets of rapamycin (mTOR) inhibitors (sirolimus [SRL] and everolimus [EVR]) are used after transplantation for their immunosuppressive activity. Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 48-52 29462337-11 2018 Conclusions: Our findings indicate that anxiety-related behavior following rapamycin treatment was not directly attributed to mTOR-dependent mechanisms or stress but rather due to hyperexcitability of the amygdala together with glucocorticoid receptor-regulated mechanism(s) in this brain region. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 126-130 29862167-7 2018 The expression of TLR4, stimulated by A. fumigatus, was reduced as well when the mTOR signaling pathway was suppressed by rapamycin. Sirolimus 122-131 mechanistic target of rapamycin kinase Homo sapiens 81-85 29736615-5 2018 The effects of BDNF were completely inhibited by rapamycin, an inhibitor of mammalian target of rapamycin (mTOR). Sirolimus 49-58 mechanistic target of rapamycin kinase Homo sapiens 76-105 29736615-5 2018 The effects of BDNF were completely inhibited by rapamycin, an inhibitor of mammalian target of rapamycin (mTOR). Sirolimus 49-58 mechanistic target of rapamycin kinase Homo sapiens 107-111 29506143-8 2018 Purified IgG from TA patients induced a significant EC proliferation compared with to GCA and HC IgG, and this effect was decreased after EC exposure with sirolimus, a specific mTOR inhibitor and PI3K inhibitor. Sirolimus 155-164 mechanistic target of rapamycin kinase Homo sapiens 177-181 29872523-3 2018 Sirolimus, a mammalian target of rapamycin inhibitor, produced rapid and dramatic improvement of the Kasabach-Merritt phenomenon and kaposiform hemangioendothelioma shrinkage. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 13-42 29532571-10 2018 As far as we know, these are the first 2 GLILD patients treated successfully with sirolimus, suggesting the advisability of further study of mTOR inhibitors as a more targeted treatment for GLILD, if impairment in Tregs is demonstrated. Sirolimus 82-91 mechanistic target of rapamycin kinase Homo sapiens 141-145 29880342-3 2018 The aim of this study was to determine the effect of sirolimus, an mTOR inhibitor, on cyst volume regression in patients with ADPKD who have undergone renal transplantation. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 67-71 29136244-4 2018 Results: An unbiased phosphoproteomic screen quantified phosphorylation changes associated with chronic exposure to the mTOR inhibitor rapamycin, and our analysis implicated a role for glycogen synthase kinase (GSK)3B attenuation in mediating resistance that was confirmed by functional studies. Sirolimus 135-144 mechanistic target of rapamycin kinase Homo sapiens 120-124 29581305-3 2018 Previous work has shown that treatment of HGPS cells with the mTOR inhibitor rapamycin or with the rapamycin analog everolimus corrects several of the phenotypes seen at the cellular level-at least in part by increasing autophagy and reducing the amount of progerin, the toxic form of lamin A that is overproduced in HGPS patients. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 62-66 29731844-6 2018 These results suggested that downregulation of the mTOR signaling cascades is likely to be a crucial mediator in the impairment of viability and the induction of apoptosis resulting from combined therapy with resveratrol and rapamycin in MM1.S cells. Sirolimus 225-234 mechanistic target of rapamycin kinase Homo sapiens 51-55 29861744-7 2018 Rapamycin-induced inhibition of mTOR decreased liver lipid accumulation at 24 h after PHx, leading to impaired LR. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 32-36 29720621-2 2018 Mammalian target of rapamycin (mTOR) is a vital modulator in cell growth control and related diseases, and we have recently demonstrated that rapamycin can suppress eosinophil differentiation in allergic airway inflammation. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 31-35 29276026-1 2018 The phosphatidylinositol 3-kinase/protein kinase B (Akt)/mechanistic target of rapamycin (PI3K/Akt/mTOR) pathway is amplified in 60-80% of patients with acute myelogenous leukemia (AML). Sirolimus 79-88 mechanistic target of rapamycin kinase Homo sapiens 99-103 29241092-2 2018 Trehalose, a naturally occurring nontoxic disaccharide found in plants, insects, microorganisms and invertebrates, but not in mammals, was reported to function as a mechanistic target of the rapamycin (mTOR)-independent inducer of autophagy. Sirolimus 191-200 mechanistic target of rapamycin kinase Homo sapiens 202-206 29524402-5 2018 PI3K inhibitor (LY 294002), ERK inhibitor (PD98059) and mTOR inhibitor (Rapamycin) inhibited ghrelin-induced A549 cell proliferation. Sirolimus 72-81 mechanistic target of rapamycin kinase Homo sapiens 56-60 29692710-7 2018 We provide further insights that explain the reasons for the failure of numerous clinical trials conducted to date targeting PI3K or mTOR complex 1 (mTORC1) with rapamycin and its analogs. Sirolimus 162-171 mechanistic target of rapamycin kinase Homo sapiens 133-137 29721158-1 2018 The mechanistic target of the rapamycin (mTOR) inhibitor, temsirolimus, has significantly improved the outcome of patients with renal cell carcinoma (RCC). Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 41-45 29636391-3 2018 We show that TPC2 is required for intracellular Ca2+ signaling in response to NAADP or to mTOR inhibition by rapamycin. Sirolimus 109-118 mechanistic target of rapamycin kinase Homo sapiens 90-94 29636391-7 2018 In HEK293 cells stably overexpressing human TPC2, shRNA-mediated knockdown of mTOR blocked rapamycin- and NAADP-evoked Ca2+ signals. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 78-82 29444470-11 2018 In addition, the hepatic phosphorylated mammalian target of rapamycin (mTOR) and P70S6K protein expressions were significantly downregulated and endothelial nitric oxide synthase (eNOS) expression upregulated by sirolimus. Sirolimus 212-221 mechanistic target of rapamycin kinase Homo sapiens 71-75 29440231-9 2018 SI-NET was more sensitive to the mTOR inhibitor sirolimus than the other solid tumor types tested. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 33-37 29351469-4 2018 We and others recently established that inhibition of the mammalian/mechanistic target of rapamycin (mTOR) pathway with rapamycin yields significant neuroprotective effects, improving cerebrovascular and cognitive function in mouse models of AD. Sirolimus 90-99 mechanistic target of rapamycin kinase Homo sapiens 101-105 29336620-3 2018 THP-1 activated cells were incubated with or without PI3K inhibitor-wortmannin or with mTOR inhibitor-rapamycin. Sirolimus 102-111 mechanistic target of rapamycin kinase Homo sapiens 87-91 29336620-11 2018 Rapamycin inhibited mTOR activation as the number of p-S6 positive cells decreased in the tested cases. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 20-24 29190547-7 2018 Treatment of H23 cells with mTOR siRNA or the mTOR inhibitor rapamycin abrogated LF-activated Akt-mTOR-Hif1-Foxo signaling and stemness-associated sonic hedgehog pathway, reversed Warburg metabolic switch and diminished invasion of H23 cells. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 46-50 29665934-9 2018 mTOR inhibitor rapamycin did not only inhibit the adipogenic differentiation of BM-MSCs from AA pateints at the early-middle stage, but also partly reversed the adipogenic differention of BM-MSCs from AA pateints at the late stage by PPARgamma regulation. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 0-4 29509701-1 2018 The mechanistic target of rapamycin (mTOR) is part of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AkT)/mTOR pathway and owes its name to the inhibitory effect of rapamycin. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 37-41 29509701-1 2018 The mechanistic target of rapamycin (mTOR) is part of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AkT)/mTOR pathway and owes its name to the inhibitory effect of rapamycin. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 114-118 29233209-4 2018 Here we report rapid regression of several massive cardiac rhadomyomas in two neonates with the use of the mammalian target of rapamycin inhibitor sirolimus. Sirolimus 147-156 mechanistic target of rapamycin kinase Homo sapiens 107-136 28969943-7 2018 The Jak 1/2 inhibitor ruxolitinib, the mTOR inhibitor rapamycin and the PI3 kinase inhibitor LY294002 all prevented the potentiation of cell death by IL-13. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 39-43 28969943-8 2018 Moreover, 4E-BP1, a target of mTOR, appeared to mediate the protective effects of rapamycin. Sirolimus 82-91 mechanistic target of rapamycin kinase Homo sapiens 30-34 29475988-8 2018 Importantly, suppression of mTORC2 for 24 h with rapamycin or everolimus or treatment with mTOR active-site inhibitors enhanced HLA-II Ab-stimulated phosphorylation of ERK. Sirolimus 49-58 mechanistic target of rapamycin kinase Homo sapiens 28-32 29247557-0 2018 Combination of melatonin and rapamycin for head and neck cancer therapy: Suppression of AKT/mTOR pathway activation, and activation of mitophagy and apoptosis via mitochondrial function regulation. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 92-96 29247557-2 2018 However, the effectiveness of treatment with the mTOR inhibitor rapamycin is often limited by chemoresistance. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 49-53 29247557-8 2018 Relationships between inhibition of the mTOR pathway, reactive oxygen species (ROS), and apoptosis and mitophagy reportedly increased the cytotoxic effects of rapamycin in HNSCC. Sirolimus 159-168 mechanistic target of rapamycin kinase Homo sapiens 40-44 29247557-9 2018 Our results demonstrated that combined treatment with rapamycin and melatonin blocked the negative feedback loop from the specific downstream effector of mTOR activation S6K1 to Akt signalling, which decreased cell viability, proliferation and clonogenic capacity. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 154-158 29619032-4 2018 Addition of the mTOR inhibitor rapamycin to Treg cultures enhances FOXP3 expression and Treg stability, but does impair proliferative capacity. Sirolimus 31-40 mechanistic target of rapamycin kinase Homo sapiens 16-20 29072256-4 2018 Knockdown of mTOR or rictor, rather than raptor, mimicked the effects of rapamycin. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 13-17 29314656-2 2018 Rapamycin is an inhibitor of serine/threonine kinase mammalian target of rapamycin (mTOR) involved in the regulation of autophagy as well as oxidative/nitrative stress. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 53-82 29314656-2 2018 Rapamycin is an inhibitor of serine/threonine kinase mammalian target of rapamycin (mTOR) involved in the regulation of autophagy as well as oxidative/nitrative stress. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 84-88 29190547-7 2018 Treatment of H23 cells with mTOR siRNA or the mTOR inhibitor rapamycin abrogated LF-activated Akt-mTOR-Hif1-Foxo signaling and stemness-associated sonic hedgehog pathway, reversed Warburg metabolic switch and diminished invasion of H23 cells. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 46-50 29328421-11 2018 It is worth noting that the inhibition of mTOR by rapamycin or of PI3K/Akt by LY294002 augmented curcumin-induced apoptosis and autophagy, leading to significant inhibition of cell proliferation. Sirolimus 50-59 mechanistic target of rapamycin kinase Homo sapiens 42-46 29087803-4 2018 Both approved mTOR inhibitors everolimus and sirolimus are widely used as immunosuppressive agents after organ transplantation. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 14-18 29424687-4 2018 We report the architecture of human mTORC2 at intermediate resolution, revealing a conserved binding site for accessory proteins on mTOR and explaining the structural basis for the rapamycin insensitivity of the complex. Sirolimus 181-190 mechanistic target of rapamycin kinase Homo sapiens 36-40 29343616-1 2018 Rapamycin, the macrolide immunosuppressant and active pharmaceutic in drug-eluting stents (DES), has a well-recognized antiproliferative action that involves inhibition of the mTOR pathway after binding to the cytosolic protein FKBP12. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 176-180 29439710-10 2018 Rapamycin, an inhibitor of AKT/mTOR, could reverse the effects of SeMet on OTA-induced autophagy and the PCV2 replication promotion. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 31-35 29146131-3 2018 Although we have already confirmed that topical rapamycin treatment (an mTOR inhibitor) protects patients with TSC against macular hypopigmentation, the pathogenesis of such lesions remains poorly understood. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 72-76 29445291-7 2018 Results: Rapamycin, AZD8055, and cardamonin inhibited the activity of mammalian target of rapamycin (mTOR). Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 70-99 29445291-7 2018 Results: Rapamycin, AZD8055, and cardamonin inhibited the activity of mammalian target of rapamycin (mTOR). Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 101-105 29160909-4 2018 Sirolimus/everolimus (mammalian target of rapamycin [mTOR] inhibitors) was added to baseline immunosuppression as rescue therapy in patients with CR. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 22-51 29160909-4 2018 Sirolimus/everolimus (mammalian target of rapamycin [mTOR] inhibitors) was added to baseline immunosuppression as rescue therapy in patients with CR. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 53-57 28488736-1 2018 Rapamycin (mTOR inhibitor) has been reported to have negative effect on human male gonadal function. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 11-15 29270715-5 2018 Furthermore, p70S6K knockdown and the specific mTOR inhibitor rapamycin decreased the expression levels of p-p70S6K and alpha-SMA in cultured fibroblasts from grade T3 pterygium. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 47-51 29434877-6 2018 Additionally, metformin (20 mmol/l) + rapamycin (200 ng/ml) significantly suppressed the expression of phosphorylated mTOR compared with metformin or rapamycin alone. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 118-122 29434854-5 2018 Additionally, the combined treatment with COE and rapamycin (an mTOR inhibitor) acted synergistically in ECA-109 cells compared with the treatment with COE or rapamycin alone. Sirolimus 50-59 mechanistic target of rapamycin kinase Homo sapiens 64-68 29434877-6 2018 Additionally, metformin (20 mmol/l) + rapamycin (200 ng/ml) significantly suppressed the expression of phosphorylated mTOR compared with metformin or rapamycin alone. Sirolimus 150-159 mechanistic target of rapamycin kinase Homo sapiens 118-122 29492193-8 2018 Our data indicate that there is a significant involvement of the mTOR network in the etiopathogenesis of MS and that Rapamycin treatment may represent a useful therapeutic approach in this clinical setting. Sirolimus 117-126 mechanistic target of rapamycin kinase Homo sapiens 65-69 28263222-3 2018 mTOR inhibitors, when used as immunosuppressive agents (sirolimus, everolimus), can induce diabetes with an incidence which is low when used without calcineurin inhibitors but high when used in combination with calcineurin inhibitors (from 11.0% to 38.1%). Sirolimus 56-65 mechanistic target of rapamycin kinase Homo sapiens 0-4 28843050-6 2018 This case contributes to the growing evidence regarding the efficacy of mTOR inhibitors, such as sirolimus, in multifocal PMH. Sirolimus 97-106 mechanistic target of rapamycin kinase Homo sapiens 72-76 29369972-3 2018 Agents that inhibit mTOR, such as sirolimus and everolimus, are incorporated in immunosuppressive regimens to prevent renal allograft rejection and are often used to facilitate calcineurin inhibitor minimization or to reduce the incidence of tumor recurrence. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 20-24 29074462-7 2018 Researchers show that mTOR inhibitor rapamycin reduces telomerase activity without changing hTERT mRNA activity. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 22-26 29382066-1 2018 Constitutive signaling through the phosphatidylinositol-3-kinase-Akt-mechanistic target of rapamycin (PI3K-Akt-mTOR) pathway is present in acute myeloid leukemia (AML) cells. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 111-115 29348392-10 2018 Our findings demonstrated that mammalian target of rapamycin (mTOR) signaling affects cellular senescence, catabolic and inflammatory responses, and multi-differentiation potential, suggesting that potential treatment value of rapamycin for disc degenerative diseases, especially lower back pain. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 62-66 29749806-2 2018 Interestingly, it has been demonstrated that in the human proximal tubular renal cell line, HK-2, the MTOR inhibitor rapamycin enhanced autophagy and mitigated the apoptosis damage induced by urinary protein overload. Sirolimus 117-126 mechanistic target of rapamycin kinase Homo sapiens 102-106 29186990-1 2018 Sirolimus (rapamycin) is a mammalian target of rapamycin (mTOR) inhibitor with immunosuppressive, antiproliferative, antiangiogenic, antifungal, anti-restenosis and anti-inflammatory properties. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-56 29186990-1 2018 Sirolimus (rapamycin) is a mammalian target of rapamycin (mTOR) inhibitor with immunosuppressive, antiproliferative, antiangiogenic, antifungal, anti-restenosis and anti-inflammatory properties. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 58-62 29186990-1 2018 Sirolimus (rapamycin) is a mammalian target of rapamycin (mTOR) inhibitor with immunosuppressive, antiproliferative, antiangiogenic, antifungal, anti-restenosis and anti-inflammatory properties. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 27-56 29186990-1 2018 Sirolimus (rapamycin) is a mammalian target of rapamycin (mTOR) inhibitor with immunosuppressive, antiproliferative, antiangiogenic, antifungal, anti-restenosis and anti-inflammatory properties. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 58-62 29975938-9 2018 However, the AMPK activator AICAR and the mTOR inhibitor rapamycin reduced the protective effects of melatonin on IRI. Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 42-46 29099279-4 2018 Pharmacological inhibition of MTOR activity by rapamycin (RPM) causes severe thymic atrophy and reduction of TECs. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 30-34 29099279-4 2018 Pharmacological inhibition of MTOR activity by rapamycin (RPM) causes severe thymic atrophy and reduction of TECs. Sirolimus 58-61 mechanistic target of rapamycin kinase Homo sapiens 30-34 28881154-4 2018 The possible role of mTOR was evaluated by the injection of rapamycin (5 mg/kg body weight, by intraperitoneal injection) before I/R was induced. Sirolimus 60-69 mechanistic target of rapamycin kinase Homo sapiens 21-25 29478616-5 2018 The mTOR inhibitors rapamycin (sirolimus) and everolimus have been shown to reduce renal and brain lesion size, and improve pulmonary function in TSC, and these compounds may also decrease seizure frequency. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 4-8 28696243-5 2018 Clinical trials using allosteric mTOR inhibitors (rapamycin and rapalogs) to treat patients with glioblastoma have also been unsuccessful or uncertain, in part, because rapamycin inefficiently blocks the mTORC1 target 4EBP1 and feeds back to activate PI3K-AKT signaling. Sirolimus 50-59 mechanistic target of rapamycin kinase Homo sapiens 33-37 29758934-3 2018 The mTOR pathway which is found to be regulated in lipomatous tissue as well as associated with brown adipose tissue can be inhibited by a compound called rapamycin. Sirolimus 155-164 mechanistic target of rapamycin kinase Homo sapiens 4-8 29190625-3 2018 Inhibition of the mTOR complex 1 (mTORC1) with rapamycin is currently the only known pharmacological treatment that increases lifespan in all model organisms studied. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 18-22 29554648-12 2018 Increased phospho-AMPKalpha, CHOP and Grp78 as well as cellular apoptosis were prevented by mTOR inhibitor rapamycin in HG-treated podocytes. Sirolimus 107-116 mechanistic target of rapamycin kinase Homo sapiens 92-96 28888335-2 2018 mTOR inhibitors (Sirolimus and Everolimus) are currently approved only for the treatment of growing subependymal giant cell astrocytomas, renal angiomyolipomas and lymphangioleiomyomatosis in TSC. Sirolimus 17-26 mechanistic target of rapamycin kinase Homo sapiens 0-4 29478616-5 2018 The mTOR inhibitors rapamycin (sirolimus) and everolimus have been shown to reduce renal and brain lesion size, and improve pulmonary function in TSC, and these compounds may also decrease seizure frequency. Sirolimus 31-40 mechanistic target of rapamycin kinase Homo sapiens 4-8 28300280-2 2018 Recently, we have reported that rapamycin, a macrocyclic lactone, attenuates human soluble BAFF (hsBAFF)-stimulated B-cell proliferation/survival by suppressing mTOR-mediated PP2A-Erk1/2 signaling pathway. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 161-165 28475412-8 2018 Importantly, a clinically used mTOR inhibitor, rapamycin, potently inhibited both experimental and patient-derived rotavirus strains. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 31-35 30779006-3 2018 Caloric restriction, the most widely studied longevity promoting intervention, works through multiple nutrient signaling pathways, while inhibition of mTOR through treatment with rapamycin reproducibly delays ageing and disease through specific inhibition of the mTOR complexes. Sirolimus 179-188 mechanistic target of rapamycin kinase Homo sapiens 151-155 30779006-3 2018 Caloric restriction, the most widely studied longevity promoting intervention, works through multiple nutrient signaling pathways, while inhibition of mTOR through treatment with rapamycin reproducibly delays ageing and disease through specific inhibition of the mTOR complexes. Sirolimus 179-188 mechanistic target of rapamycin kinase Homo sapiens 263-267 30056926-0 2018 Efficacy and Safety of Mammalian Target of Rapamycin Inhibitor Use-Long-term Follow-up of First Tuberous Sclerosis Complex Patient Treated De Novo With Sirolimus After Kidney Transplantation: A Case Report. Sirolimus 152-161 mechanistic target of rapamycin kinase Homo sapiens 23-52 29287601-8 2017 RESULTS: Inhibition of mTOR signaling using rapamycin enhanced the immunosuppressive functions of MSCs, while prolonged exposure to rapamycin did not. Sirolimus 44-53 mechanistic target of rapamycin kinase Homo sapiens 23-27 29162840-0 2017 Whey Protein Concentrate Renders MDA-MB-231 Cells Sensitive to Rapamycin by Altering Cellular Redox State and Activating GSK3beta/mTOR Signaling. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 130-134 29056443-8 2017 Further, we report on successful co-loading of 17-AAG (Hsp90) and rapamycin (mTOR) (g-EAR). Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 77-81 29246172-1 2017 We first introduced the concept of the mTOR pathway"s involvement in congenital hyperinsulinism of infancy (CHI), based largely on morphoproteomic observations and clinical outcomes using sirolimus (rapamycin) as a therapeutic agent in infants refractory to octreotide and diazoxide treatment. Sirolimus 188-197 mechanistic target of rapamycin kinase Homo sapiens 39-43 29246172-1 2017 We first introduced the concept of the mTOR pathway"s involvement in congenital hyperinsulinism of infancy (CHI), based largely on morphoproteomic observations and clinical outcomes using sirolimus (rapamycin) as a therapeutic agent in infants refractory to octreotide and diazoxide treatment. Sirolimus 199-208 mechanistic target of rapamycin kinase Homo sapiens 39-43 29269724-1 2017 BACKGROUND Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor, which is used in immunosuppressive treatment regimens in organ transplant recipients. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 26-55 29269724-1 2017 BACKGROUND Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor, which is used in immunosuppressive treatment regimens in organ transplant recipients. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 57-61 29021448-1 2017 Recently, sirolimus, an inhibitor of mammalian target of rapamycin, was reported to decrease chylous effusion in patients with lymphangioleimyomatosis (LAM). Sirolimus 10-19 mechanistic target of rapamycin kinase Homo sapiens 37-66 29040365-8 2017 Meanwhile, rapamycin, an mTOR inhibitor, reversed the increased cell proliferation induced by the HPV11 L1-L2 plasmid. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 25-29 27860549-4 2017 Our findings suggest five novel potential mTOR inhibitors, with similar or better properties than the classic inhibitor complex, rapamycin. Sirolimus 129-138 mechanistic target of rapamycin kinase Homo sapiens 42-46 29078414-1 2017 In my PNAS Inaugural Article, I describe the development of the mTOR field, starting with efforts to understand the mechanism of action of the drug rapamycin, which ~25 y ago led to the discovery of the mTOR protein kinase. Sirolimus 148-157 mechanistic target of rapamycin kinase Homo sapiens 64-68 29165314-2 2017 Metformin and rapamycin are two FDA-approved mTOR inhibitors proposed for this purpose, exhibiting significant anti-cancer and anti-aging properties beyond their current clinical applications. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 45-49 29078414-1 2017 In my PNAS Inaugural Article, I describe the development of the mTOR field, starting with efforts to understand the mechanism of action of the drug rapamycin, which ~25 y ago led to the discovery of the mTOR protein kinase. Sirolimus 148-157 mechanistic target of rapamycin kinase Homo sapiens 203-207 28220552-9 2017 Furthermore, when the mTOR inhibitor rapamycin was administered with ketamine to the HBdMECs, the expression of FSP-1 decreased significantly. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 22-26 28903183-4 2017 Rapamycin is a well-know potent antiangiogenic agent, whereas the daily oral administration of rapamycin exerts undesired metabolic effects due to its inhibition of mechanistic target of rapamycin (mTOR) which is critical in cell metabolism. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 198-202 28903183-4 2017 Rapamycin is a well-know potent antiangiogenic agent, whereas the daily oral administration of rapamycin exerts undesired metabolic effects due to its inhibition of mechanistic target of rapamycin (mTOR) which is critical in cell metabolism. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 165-196 28903183-4 2017 Rapamycin is a well-know potent antiangiogenic agent, whereas the daily oral administration of rapamycin exerts undesired metabolic effects due to its inhibition of mechanistic target of rapamycin (mTOR) which is critical in cell metabolism. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 198-202 28916337-13 2017 Rapamycin can enhance the level of autophagy by inhibiting mTOR, and 3-methyladenine (3-MA) can inhibit autophagosome formation through blocking class III phosphatidylinositol 3-kinase. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 59-63 28882485-9 2017 Both the phosphatidylinositol 3-kinase (PI3K) inhibitor LY 294002 and the mammalian target of rapamycin (mTOR) inhibitor rapamycin abolished ZnCl2-induced transport stimulation. Sirolimus 94-103 mechanistic target of rapamycin kinase Homo sapiens 105-109 28836710-2 2017 We present a 9-year-old girl, remote from transplant, who presented with airway plaque after a change in immunosuppression to include the mTOR inhibitor sirolimus. Sirolimus 153-162 mechanistic target of rapamycin kinase Homo sapiens 138-142 28807764-6 2017 However, SEC2/ST-4-induced changes in cell cycle and PI3K/mTOR signaling were significantly relieved by either LY294002 or rapamycin, and the induction of NF-kB/p65 induced was significantly downregulated by Bay11-7085. Sirolimus 123-132 mechanistic target of rapamycin kinase Homo sapiens 58-62 29085896-1 2017 Following traumatic brain injury (TBI), treatment with rapamycin suppresses mammalian (mechanistic) target of rapamycin (mTOR) activity and specific components of hippocampal synaptic reorganization associated with altered cortical excitability and seizure susceptibility. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 121-125 28514891-3 2017 Herein, we have investigated the beneficial effect of cotreatment with CRM-candidate drugs, rapamycin (an immunosuppressant drug and inhibitor of mammalian target of rapamycin) and metformin (an antidiabetic biguanide and activator of adenosine monophosphate kinase), against aging-induced oxidative stress in erythrocytes and plasma of aging rats. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 146-175 31966350-2 2017 Rapamycin (RAPA), a highly specific inhibitor of mTOR, is widely used in cancer studies for its antiangiogenic activity. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 49-53 31966350-2 2017 Rapamycin (RAPA), a highly specific inhibitor of mTOR, is widely used in cancer studies for its antiangiogenic activity. Sirolimus 11-15 mechanistic target of rapamycin kinase Homo sapiens 49-53 28608572-9 2017 Among the missense mutations, one in the rapamycin-insensitive companion of mammalian target of rapamycin (RICTOR)-coding gene (rs140964083: G > A, found in one proband) was predicted to be hazardous. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 76-105 28993730-8 2017 However, targeting the altered biological pathways (mTOR, PDGFRB, FGF2, HDAC) guided identification of possibly beneficial treatment with a combination of sirolimus, thalidomide, sunitinib, and vorinostat. Sirolimus 155-164 mechanistic target of rapamycin kinase Homo sapiens 52-56 29070114-0 2017 [Effects of mTOR Inhibitor Rapamycin on Burkitt"s Lymphoma Cells]. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 12-16 29070114-1 2017 OBJECTIVE: To explore the effects of mTOR inhibitor rapamycin on proliferation, cell cycle and apoptosis of Burkitt"s lymphoma cell line Raji and CA46 cells and its mechanism, so as to provide the experimental evidence for a therapeutic target of Burkitt"s lymphoma. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 37-41 28931653-3 2017 Conversely, mechanistic target of rapamycin (mTOR) inhibition with sirolimus is more Treg-compatible but is inadequate to fully control Teff activation. Sirolimus 67-76 mechanistic target of rapamycin kinase Homo sapiens 12-43 28931653-3 2017 Conversely, mechanistic target of rapamycin (mTOR) inhibition with sirolimus is more Treg-compatible but is inadequate to fully control Teff activation. Sirolimus 67-76 mechanistic target of rapamycin kinase Homo sapiens 45-49 28734155-6 2017 The mTOR inhibitor rapamycin (100nM) could attenuate the elevated expression of TF and IL-8. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 28765952-9 2017 Rapamycin, an mTOR inhibitor, suppressed the expression and activity of mTOR and p70S6K, however enhanced expression of SIRT1, LXRalpha, and CCR7. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 28765952-9 2017 Rapamycin, an mTOR inhibitor, suppressed the expression and activity of mTOR and p70S6K, however enhanced expression of SIRT1, LXRalpha, and CCR7. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 72-76 28926611-2 2017 Here, we report that the mTOR inhibitors rapamycin (sirolimus) and structurally related temsirolimus are capable of inducing UPR in sarcoma cells. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 25-29 28926611-2 2017 Here, we report that the mTOR inhibitors rapamycin (sirolimus) and structurally related temsirolimus are capable of inducing UPR in sarcoma cells. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 25-29 28724580-10 2017 mTOR activation was central to this process, because rapamycin systematically inhibited the beneficial effect of recombinant human IL-7. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 0-4 28566443-5 2017 Signalling in dermal fibroblasts from one patient and efficacy of the mTOR inhibitor Sirolimus on pathway activation were examined. Sirolimus 85-94 mechanistic target of rapamycin kinase Homo sapiens 70-74 29152091-8 2017 The mTOR inhibitor Rapamycin prevented FGF-2 protection, and blocked the FGF-2 effects on Nrf-2, HO-1 and p62/SQSTM1. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 28831455-2 2017 One potential and current model that explains Akt activation induced by the mTOR inhibitor rapamycin is the relief of mTORC1/p70S6K-mediated feedback inhibition of IRS-1/PI3K/Akt signaling, although this has not been experimentally proven. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 76-80 28768489-12 2017 The newly predicted drug responses of GDSC dataset suggest that mTOR inhibitor rapamycin was sensitive to non-small cell lung cancer (NSCLC), and expression of AK1RC3 and HINT1 may be adjunct markers of cell line sensitivity to rapamycin. Sirolimus 79-88 mechanistic target of rapamycin kinase Homo sapiens 64-68 28528119-7 2017 Specifically, the mTOR-dependent autophagy inducer rapamycin enhanced the knockdown efficiency of both lipoplex and polyplex, whereas mTOR-dependent autophagy inhibitor 3-methyladenine (3-MA) suppressed their silencing efficiency. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 18-22 28167236-4 2017 Rapamycin, an inhibitor of mTOR that increases longevity in several species, inhibits cell senescence in vitro, while silencing the Nrf2 gene induces premature senescence. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 28665070-3 2017 We validated mTOR downstream genes with immunohistochemistry using a tissue microarray (TMA) of 125 non-muscle invasive HG-UC patients and knockout study to evaluate the synergistic effect with rapamycin. Sirolimus 194-203 mechanistic target of rapamycin kinase Homo sapiens 13-17 28819418-12 2017 Conclusions: Our results suggest that CENPH inhibits rapamycin sensitivity by regulating GOLPH3 dependent mTOR pathway. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 106-110 28507054-8 2017 In contrast, rapamycin was able to decrease the androgen-mediated expression of SLC1A4 and SLC1A5 independent of PTEN status, indicating that mTOR complex 1 (mTORC1) was needed for maximal AR-mediated glutamine uptake and prostate cancer cell growth. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 142-146 28724379-11 2017 The c-MYC inhibitor, the PI3K inhibitor LY294002, the mTOR inhibitor Rapamycin and 2-DG all diminished the number of viable cells. Sirolimus 69-78 mechanistic target of rapamycin kinase Homo sapiens 54-58 28724388-6 2017 Inhibition of MTOR by rapamycin decreased basal levels of protein O-GlcNAcylation, decreased AKT activation and partially reversed the effect of thiamet G on alpha-synuclein monomer accumulation. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 28698309-5 2017 The concept that mTOR has a crucial role in ageing is supported by numerous reports on the lifespan-prolonging effects of the mTOR inhibitor rapamycin in invertebrate and vertebrate model organisms. Sirolimus 141-150 mechanistic target of rapamycin kinase Homo sapiens 17-21 28698309-5 2017 The concept that mTOR has a crucial role in ageing is supported by numerous reports on the lifespan-prolonging effects of the mTOR inhibitor rapamycin in invertebrate and vertebrate model organisms. Sirolimus 141-150 mechanistic target of rapamycin kinase Homo sapiens 126-130 28484962-3 2017 Recent studies demonstrate treatment with rapamycin-a key inhibitor of the mTOR pathway-can skew T cell development, moving T cell responses away from inflammatory phenotypes and toward regulatory T cells (TREGS). Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 75-79 28525374-6 2017 We assessed the therapeutic effects of four compounds (rapamycin, NVP-BEZ235, aspirin, and metformin) on PI3K/AKT/mTOR signaling pathway and cell growth. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 114-118 28595829-5 2017 We report on six cases of complicated VAs, refractory to current treatments, treated with rapamycin, an mTor inhibitor recently used in VAs. Sirolimus 90-99 mechanistic target of rapamycin kinase Homo sapiens 104-108 28217909-3 2017 Reversion of the atrial ectopic tachycardia was achieved with mammalian target of rapamycin pathway (mTOR) inhibitor sirolimus. Sirolimus 117-126 mechanistic target of rapamycin kinase Homo sapiens 62-91 28217909-3 2017 Reversion of the atrial ectopic tachycardia was achieved with mammalian target of rapamycin pathway (mTOR) inhibitor sirolimus. Sirolimus 117-126 mechanistic target of rapamycin kinase Homo sapiens 101-105 28560385-8 2017 Inhibition of mTOR with rapamycin promoted autophagy and viral mRNA replication but did not impact VP1 expression. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 14-18 28579603-9 2017 Immunohistochemistry of the cysts demonstrated a high level of phosphorylation of p70S6 kinase, a downstream mTOR target, and since a target therapy that blocks PI3K/Akt/mTOR pathway has been shown to have a scientific and logical rationale to treat this rare intra-abdominal neoplasia, we started the patient on low dose rapamycin therapy, an mTOR inhibitor. Sirolimus 322-331 mechanistic target of rapamycin kinase Homo sapiens 170-174 28663780-4 2017 Development of the mTOR inhibitors everolimus and sirolimus has led to considerable progress in the treatment of renal angiomyolipomata, pulmonary lymphangioleiomyomatosis, and subependymal giant cell astrocytomas in the brain. Sirolimus 50-59 mechanistic target of rapamycin kinase Homo sapiens 19-23 28706974-1 2017 BACKGROUND: Kidney transplant recipients (KTRs) receiving the mammalian target of rapamycin inhibitor sirolimus may display a reduced risk of skin cancer development compared to KTRs receiving calcineurin inhibitors. Sirolimus 102-111 mechanistic target of rapamycin kinase Homo sapiens 62-91 28134984-2 2017 The mTOR inhibitor sirolimus was used in selected liver graft recipients despite safety concerns and lack of approval. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 28579603-9 2017 Immunohistochemistry of the cysts demonstrated a high level of phosphorylation of p70S6 kinase, a downstream mTOR target, and since a target therapy that blocks PI3K/Akt/mTOR pathway has been shown to have a scientific and logical rationale to treat this rare intra-abdominal neoplasia, we started the patient on low dose rapamycin therapy, an mTOR inhibitor. Sirolimus 322-331 mechanistic target of rapamycin kinase Homo sapiens 170-174 28579603-11 2017 CONCLUSIONS The current case is the first report of BMPM successfully treated with rapamycin, which resulted in a long-lasting response to mTOR inhibition. Sirolimus 83-92 mechanistic target of rapamycin kinase Homo sapiens 139-143 27915965-7 2017 The mammalian target of rapamycin inhibitors everolimus and sirolimus are preferred due to their complementary mechanisms of action and favorable nephrotoxicity profile, which have opened the way for calcineurin inhibitor reduction/withdrawal in the early posttransplant period. Sirolimus 60-69 mechanistic target of rapamycin kinase Homo sapiens 4-33 28434143-5 2017 While short-term treatment with rapamycin, an mTOR inhibitor, is a promising strategy for cardiac diseases such as acute myocardial infarction and cardiac hypertrophy in T2DM, there are many concerns about chronic usage of rapamycin. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 46-50 28254579-1 2017 Previous work revealed that intracellular Ca2+ signals and the inositol 1,4,5-trisphosphate (IP3) receptors (IP3R) are essential to increase autophagic flux in response to mTOR inhibition, induced by either nutrient starvation or rapamycin treatment. Sirolimus 230-239 mechanistic target of rapamycin kinase Homo sapiens 172-176 28542147-10 2017 In addition, the NGF inhibitor K252a and the mTOR inhibitor rapamycin constitute good candidates for protecting follicular reserve against over exhaustion after ovarian surgery. Sirolimus 60-69 mechanistic target of rapamycin kinase Homo sapiens 45-49 28238805-7 2017 Interestingly, the LSD1 inhibitor, RN-1, and the mitophagy-inducing agent mammalian target of rapamycin (mTOR) inhibitor, sirolimus, increased RBC lifespan and reduced ROS accumulation in parallel with reducing mitochondria-retaining RBCs in the SCD mouse model. Sirolimus 122-131 mechanistic target of rapamycin kinase Homo sapiens 74-103 28238805-7 2017 Interestingly, the LSD1 inhibitor, RN-1, and the mitophagy-inducing agent mammalian target of rapamycin (mTOR) inhibitor, sirolimus, increased RBC lifespan and reduced ROS accumulation in parallel with reducing mitochondria-retaining RBCs in the SCD mouse model. Sirolimus 122-131 mechanistic target of rapamycin kinase Homo sapiens 105-109 28548953-1 2017 Inhibitors of mTOR, including clinically available rapalogs such as rapamycin (Sirolimus) and Everolimus, are gerosuppressants, which suppress cellular senescence. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 14-18 28548953-1 2017 Inhibitors of mTOR, including clinically available rapalogs such as rapamycin (Sirolimus) and Everolimus, are gerosuppressants, which suppress cellular senescence. Sirolimus 79-88 mechanistic target of rapamycin kinase Homo sapiens 14-18 28573133-5 2017 Inhibition of mTOR with rapamycin (10 nM) significantly interfered with all aspects of osteoclastogenesis. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 14-18 28450865-3 2017 Inhibition of mTOR complex 1 by rapamycin revealed the immunosuppressive activity of Dex was independent from the effect of enhancing NK cell proliferation. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 14-18 28186963-7 2017 In addition, B392 enhanced the cytotoxicity of sirolimus in sirolimus-resistant acute leukemic cells through inhibition of Akt/mTOR pathway and Mcl-1 protein expression, and also was active in the p-glycoprotein (p-gp)-overexpressing National Cancer Institute/Adriamycin-Resistant cells with little susceptibility to p-gp. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 127-131 28507917-6 2017 The mTOR inhibitors such as everolimus and sirolimus, due to their complementary mechanism of action and favourable nephrotoxicity profile; better glomerular filtration, lower serum creatinine with equivalent survival. Sirolimus 43-52 mechanistic target of rapamycin kinase Homo sapiens 4-8 28514674-4 2017 We also discuss the impact of metabolic constraints in tissues on immune homeostasis and disease, and how manipulating mTOR activity with drugs such as rapamycin can modulate immunity in these contexts. Sirolimus 152-161 mechanistic target of rapamycin kinase Homo sapiens 119-123 28418837-3 2017 Therefore, in the present study we administered different doses of the mTOR inhibitor rapamycin to explore whether the transcription of specific genes are modified. Sirolimus 86-95 mechanistic target of rapamycin kinase Homo sapiens 71-75 28250148-6 2017 Systemic rapamycin treatment, thought to selectively target mTOR complex 1 (mTORC1), suppressed mTOR/S6 signaling, reduced levels of MBP and overall tubulin, and decreased NF-H phosphorylation in nerves strained for 6 h, revealing a role for mTOR in increasing MBP expression and NF-H phosphorylation, and maintaining tubulin levels. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 60-64 28250148-6 2017 Systemic rapamycin treatment, thought to selectively target mTOR complex 1 (mTORC1), suppressed mTOR/S6 signaling, reduced levels of MBP and overall tubulin, and decreased NF-H phosphorylation in nerves strained for 6 h, revealing a role for mTOR in increasing MBP expression and NF-H phosphorylation, and maintaining tubulin levels. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 76-80 28250148-6 2017 Systemic rapamycin treatment, thought to selectively target mTOR complex 1 (mTORC1), suppressed mTOR/S6 signaling, reduced levels of MBP and overall tubulin, and decreased NF-H phosphorylation in nerves strained for 6 h, revealing a role for mTOR in increasing MBP expression and NF-H phosphorylation, and maintaining tubulin levels. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 76-80 28119225-8 2017 Combination therapy with rapamycin, an mTOR inhibitor, and BTdCPU, an activator of HRI, demonstrated additive effects on apoptosis in dex-resistant cells. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 39-43 28104700-2 2017 The second generation of mTOR kinase inhibitors (TORKi), directly targeting the mTOR catalytic site, are more effective than rapamycin and its analogs in cancer treatment, particularly in inducing apoptosis. Sirolimus 125-134 mechanistic target of rapamycin kinase Homo sapiens 25-29 28317380-8 2017 The Ingenuity Systems software identified 16 pathways, and this analysis indicated sirolimus, an mTOR pathway inhibitor, as a potential inhibitor of CypA. Sirolimus 83-92 mechanistic target of rapamycin kinase Homo sapiens 97-101 28379293-4 2017 We recently found that RA stimulation of the Phosphatidylinositol 3-kinase (PI3K)/AKT/Mammalian target of rapamycin (mTOR) kinase signaling pathway is required for differentiation, and that short-term inhibition of mTOR complex 1 (mTORC1) by rapamycin blocked spermatogonial differentiation in vivo and prevented RA-induced translational activation. Sirolimus 106-115 mechanistic target of rapamycin kinase Homo sapiens 117-121 28386356-13 2017 Similar to FA, downregulation of mTOR signaling by rapamycin inhibited VSMC dedifferentiation. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 33-37 28209733-7 2017 Rapamycin had the converse effect, linking MTOR signaling to induction of fiber cell differentiation by TGFbeta. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 43-47 31988901-4 2017 Herein, we report a premature neonate at the gestational age of 30 + 4 weeks with severe left ventricular outflow tract obstructive cardiac rhabdomyoma who was successfully treated with the mTOR inhibitor sirolimus. Sirolimus 205-214 mechanistic target of rapamycin kinase Homo sapiens 190-194 28333142-7 2017 Like rapamycin, NaHS also significantly inhibited expression of p-PI3K, p-Akt and mTOR proteins in HCC cells. Sirolimus 5-14 mechanistic target of rapamycin kinase Homo sapiens 82-86 28027414-7 2017 Upstream of p62, we found that BDNF triggered phosphorylation of mammalian target of rapamycin (mTOR) and its downstream mediator p70S6K; importantly, the mTOR inhibitor rapamycin reduced both BDNF-dependent p62 induction as well as 3-NP resistance. Sirolimus 85-94 mechanistic target of rapamycin kinase Homo sapiens 96-100 28292440-2 2017 Allosteric mTOR inhibitors, such as rapamycin, incompletely block mTORC1 compared with mTOR kinase inhibitors (TORKi). Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 11-15 28292440-2 2017 Allosteric mTOR inhibitors, such as rapamycin, incompletely block mTORC1 compared with mTOR kinase inhibitors (TORKi). Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 66-70 28292440-6 2017 RapaLink-1 showed better efficacy than rapamycin or TORKi, potently blocking cancer-derived, activating mutants of mTOR. Sirolimus 39-48 mechanistic target of rapamycin kinase Homo sapiens 115-119 28257428-11 2017 mTOR phosphorylation can be decreased by the mTOR antagonist, rapamycin. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 0-4 28257428-11 2017 mTOR phosphorylation can be decreased by the mTOR antagonist, rapamycin. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 45-49 28181194-2 2017 Here we report the case of a 12-year-old girl with widespread disfiguring facial angiofibromas that were successfully treated with topical rapamycin, a mTOR inhibitor. Sirolimus 139-148 mechanistic target of rapamycin kinase Homo sapiens 152-156 28400999-1 2017 The mTOR pathway was discovered in the late 1970s after the compound and natural inhibitor of mTOR, rapamycin was isolated from the bacterium Streptomyces hygroscopicus. Sirolimus 100-109 mechanistic target of rapamycin kinase Homo sapiens 4-8 28400999-1 2017 The mTOR pathway was discovered in the late 1970s after the compound and natural inhibitor of mTOR, rapamycin was isolated from the bacterium Streptomyces hygroscopicus. Sirolimus 100-109 mechanistic target of rapamycin kinase Homo sapiens 94-98 28027414-7 2017 Upstream of p62, we found that BDNF triggered phosphorylation of mammalian target of rapamycin (mTOR) and its downstream mediator p70S6K; importantly, the mTOR inhibitor rapamycin reduced both BDNF-dependent p62 induction as well as 3-NP resistance. Sirolimus 85-94 mechanistic target of rapamycin kinase Homo sapiens 155-159 28260460-1 2017 The mammalian target of rapamycin inhibitor sirolimus was introduced into clinical transplant practice in 1999. Sirolimus 44-53 mechanistic target of rapamycin kinase Homo sapiens 4-33 28243129-13 2017 Furthermore, inhibition of the mTOR/p70s6k signaling pathway by rapamycin significantly induced autophagy and apoptosis and inhibited cell viability (P<0.05). Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 31-35 28367235-3 2017 Thus, rapamycin, as an mTOR specific inhibitor, has been assumed as a potential drug for the treatment of TSC. Sirolimus 6-15 mechanistic target of rapamycin kinase Homo sapiens 23-27 28182765-8 2017 Furthermore, osteogenesis of MC3T3-E1 showed significant association with the mammalian target of rapamycin (mTOR) phosphorylation by RA, which required further study about the mechanism. Sirolimus 134-136 mechanistic target of rapamycin kinase Homo sapiens 78-107 28182765-8 2017 Furthermore, osteogenesis of MC3T3-E1 showed significant association with the mammalian target of rapamycin (mTOR) phosphorylation by RA, which required further study about the mechanism. Sirolimus 134-136 mechanistic target of rapamycin kinase Homo sapiens 109-113 27990590-4 2017 Blood was collected at baseline and then 6 and 12 months after treatment with the mTOR inhibitor sirolimus. Sirolimus 97-106 mechanistic target of rapamycin kinase Homo sapiens 82-86 27862340-2 2017 Recently, mTOR inhibitors such as sirolimus and everolimus (EVR) have been used with or without CNIs in LT recipients for their renal-sparing effect. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 10-14 28439198-11 2017 mTOR inhibitors such as everolimus and sirolimus have been increasingly used in the treatment of these tumors. Sirolimus 39-48 mechanistic target of rapamycin kinase Homo sapiens 0-4 27225870-4 2017 In this study, we asked whether combination treatment with rapamycin and resveratrol could be effective in concurrently inhibiting mTOR and PI3K signaling and inducing cell death in bladder cancer cells. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 131-135 27974559-8 2017 Together, these findings demonstrate that mTOR signals play an essential role in antigen-specific humoral immune responses by differentially regulating B cell and CD4 T cell responses during acute viral infection and that rapamycin treatment alters the interplay of immune cell subsets involved in antiviral humoral immunity. Sirolimus 222-231 mechanistic target of rapamycin kinase Homo sapiens 42-46 28028691-4 2017 To investigate the mechanism for the variability in the change in PCSK9 levels, lymphoblastoid cell lines were incubated with both sirolimus and everolimus, resulting in a 2-3 fold increase in PCSK9 expression and protein levels in mTOR inhibitor sensitive but not in mTOR inhibitor resistant cell lines. Sirolimus 131-140 mechanistic target of rapamycin kinase Homo sapiens 232-236 28028691-4 2017 To investigate the mechanism for the variability in the change in PCSK9 levels, lymphoblastoid cell lines were incubated with both sirolimus and everolimus, resulting in a 2-3 fold increase in PCSK9 expression and protein levels in mTOR inhibitor sensitive but not in mTOR inhibitor resistant cell lines. Sirolimus 131-140 mechanistic target of rapamycin kinase Homo sapiens 268-272 27585353-5 2017 MTOR inhibitors such as Everolimus or Sirolimus are implemented in the treatment of TSC/LAM and found to control disease burden. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 0-4 28094770-3 2017 Here, we have explored a strategy that involves a combination of immune activation and the immunosuppressive mTOR inhibitor rapamycin. Sirolimus 124-133 mechanistic target of rapamycin kinase Homo sapiens 109-113 27914823-12 2017 Moreover, rapamycin (10nM) inhibited mTOR-FABP4 signaling and HemEC proliferation. Sirolimus 10-19 mechanistic target of rapamycin kinase Homo sapiens 37-41 28031240-4 2017 Western blotting analysis demonstrated that the inhibitory effect of STX-0119 on S6 and 4E-BP1 activation through regulation of YKL-40 expression occurred in addition to the inhibitory effect of rapamycin against the mTOR pathway. Sirolimus 195-204 mechanistic target of rapamycin kinase Homo sapiens 217-221 28100577-2 2017 Its physiopathology is unclear but there might be an association with mammalian target of rapamycin (m-TOR) inhibitors, especially in patients with chronic hepatitis C. We report a case of late spontaneous decapsulation 12 years after kidney transplant in a patient infected with hepatitis C under treatment with sirolimus. Sirolimus 313-322 mechanistic target of rapamycin kinase Homo sapiens 70-99 28078989-2 2017 There is a need for efficacious steroid-sparing immunomodulatory therapy for these patients, and the mTOR inhibitors (sirolimus and everolimus) may be contenders for this role. Sirolimus 118-127 mechanistic target of rapamycin kinase Homo sapiens 101-105 27764525-9 2017 Inhibition of mTOR with rapamycin or knockdown of mTOR potentiated prevention by celastrol, of Cd-induced phosphorylation of p70 S6 kinase 1/eukaryotic initiation factor 4E binding protein 1 and apoptosis. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 14-18 28214861-11 2017 Both the Akt inhibitor MK2206 and mTOR inhibitor rapamycin further increased TNF-alpha-induced VAF autophagy. Sirolimus 49-58 mechanistic target of rapamycin kinase Homo sapiens 34-38 28848090-13 2017 All effects were offset by pretreating with rapamycin (an mTOR antagonist). Sirolimus 44-53 mechanistic target of rapamycin kinase Homo sapiens 58-62 28721811-7 2017 Interestingly, the circadian clock system relies upon the regulation of the critical pathways of autophagy, the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) as well as proliferative mechanisms that involve the wingless pathway of Wnt/beta-catenin pathway to foster cell survival during injury and block tumor cell growth. Sirolimus 134-143 mechanistic target of rapamycin kinase Homo sapiens 145-149 28386314-3 2017 The establishment of a connection between TSC and mTOR led to the clinical use of drugs known as mTOR inhibitors (like rapamycin, also known as sirolimus and everolimus), which are becoming an increasingly interesting tool in the management of TSC-associated features, such as subependymal giant cell astrocytomas, renal angiomyolipomas, and also epilepsy. Sirolimus 119-128 mechanistic target of rapamycin kinase Homo sapiens 50-54 28487599-8 2017 Furthermore, rapamycin, a specific inhibitor of the mTOR/p70S6K signaling pathway, decreased the levels of Ki-67 and Bcl-2/Bax ratio, inhibited cell proliferation, and promoted apoptosis in EC cells. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 52-56 28035937-10 2017 Rapamycin decreased phospho-mTOR and to lesser degree p-Rictor. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 28-32 27690737-3 2017 Areas covered: In this review, we report all the current findings on the use of mTOR inhibitors (rapamycin, rapalogues) in the treatment of AD. Sirolimus 97-106 mechanistic target of rapamycin kinase Homo sapiens 80-84 27807044-1 2017 Golgi-specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 98-102 28191279-8 2017 These effects were inhibited by the PI3K inhibitor LY294002, the AKT inhibitor triciribine, the mTOR inhibitor rapamycin, mTOR siRNA, and N-acetyl cysteine. Sirolimus 111-120 mechanistic target of rapamycin kinase Homo sapiens 96-100 28386314-3 2017 The establishment of a connection between TSC and mTOR led to the clinical use of drugs known as mTOR inhibitors (like rapamycin, also known as sirolimus and everolimus), which are becoming an increasingly interesting tool in the management of TSC-associated features, such as subependymal giant cell astrocytomas, renal angiomyolipomas, and also epilepsy. Sirolimus 119-128 mechanistic target of rapamycin kinase Homo sapiens 97-101 28386314-3 2017 The establishment of a connection between TSC and mTOR led to the clinical use of drugs known as mTOR inhibitors (like rapamycin, also known as sirolimus and everolimus), which are becoming an increasingly interesting tool in the management of TSC-associated features, such as subependymal giant cell astrocytomas, renal angiomyolipomas, and also epilepsy. Sirolimus 144-153 mechanistic target of rapamycin kinase Homo sapiens 50-54 28386314-3 2017 The establishment of a connection between TSC and mTOR led to the clinical use of drugs known as mTOR inhibitors (like rapamycin, also known as sirolimus and everolimus), which are becoming an increasingly interesting tool in the management of TSC-associated features, such as subependymal giant cell astrocytomas, renal angiomyolipomas, and also epilepsy. Sirolimus 144-153 mechanistic target of rapamycin kinase Homo sapiens 97-101 28400912-9 2017 Finally, MTOR inhibition by Rapamycin, everolimus, or pp242 did not affect the series of biological events in keratinocytes exposed to UVB, including the downregulation of BiP and PERK, activation of Histone H2A and JNK, and cleavage of caspase-3 and PARP. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 9-13 27547865-5 2017 The mammalian target of rapamycin (mTOR) inhibitors, sirolimus and everolimus, are increasingly used after organ transplantation with potential advantages in virus-associated posttransplant malignancies as well as anti-cancer properties. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 4-33 27547865-5 2017 The mammalian target of rapamycin (mTOR) inhibitors, sirolimus and everolimus, are increasingly used after organ transplantation with potential advantages in virus-associated posttransplant malignancies as well as anti-cancer properties. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 35-39 27989873-11 2016 PGB treatment increased the phosphorylation of AMP-activated protein kinase (AMPK) and subsequently suppressed the AKT/mammalian target of the rapamycin (mTOR) pathway. Sirolimus 143-152 mechanistic target of rapamycin kinase Homo sapiens 154-158 27769712-0 2016 CWF-145, a novel synthetic quinolone derivative exerts potent antimitotic activity against human prostate cancer: Rapamycin enhances antimitotic drug-induced apoptosis through the inhibition of Akt/mTOR pathway. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 198-202 28053551-6 2017 The mTOR inhibitors rapamycin (sirolimus) and everolimus have been shown to reduce the size of renal and brain lesions and improve pulmonary function in TSC, and these compounds may also decrease seizure frequency. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 4-8 27769712-10 2016 Interestingly, rapamycin inhibited Akt-mediated therapeutic resistance, indicating that these effects were dependent on mTOR. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 120-124 28053551-6 2017 The mTOR inhibitors rapamycin (sirolimus) and everolimus have been shown to reduce the size of renal and brain lesions and improve pulmonary function in TSC, and these compounds may also decrease seizure frequency. Sirolimus 31-40 mechanistic target of rapamycin kinase Homo sapiens 4-8 27713162-6 2016 The association between tumor drug resistance and the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K-AKT-mTOR) pathway was measured by western blot, assessing the changes in protein kinase B (AKT), phosphor-AKT (p-AKT), P70, and p-P70 protein levels. Sirolimus 123-132 mechanistic target of rapamycin kinase Homo sapiens 143-147 27342399-8 2016 CONCLUSIONS: Metastatic competence of osteosarcoma cells is dependent on efficient mRNA translation during stressful periods of metastatic progression, and the mTOR inhibitor, rapamycin, can mitigate this translation and inhibit metastasis in vivo Our data suggest that mTOR pathway inhibitors should be reconsidered in the clinic using rationally designed dosing schedules and clinical metrics related to metastatic progression. Sirolimus 176-185 mechanistic target of rapamycin kinase Homo sapiens 160-164 27992581-7 2016 Inhibition of autophagy by 3-methyladenine shortens the transient phase, while inhibition of mTOR by rapamycin or resveratrol prolongs it. Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 93-97 27342399-8 2016 CONCLUSIONS: Metastatic competence of osteosarcoma cells is dependent on efficient mRNA translation during stressful periods of metastatic progression, and the mTOR inhibitor, rapamycin, can mitigate this translation and inhibit metastasis in vivo Our data suggest that mTOR pathway inhibitors should be reconsidered in the clinic using rationally designed dosing schedules and clinical metrics related to metastatic progression. Sirolimus 176-185 mechanistic target of rapamycin kinase Homo sapiens 270-274 27691052-3 2016 Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been reported to obviate the need for pancreatectomy, but experience is limited. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 13-42 27566137-7 2016 Treatment with rapamycin and PP242, that target the PI3K/AKT/mTOR signaling pathway, modified starvation-induced autophagy and apoptosis in IPF fibroblasts. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 61-65 27815691-2 2016 The mTOR pathway has become an exciting treatment target for these various disorders, with mTOR inhibitors such as rapamycin being studied for their potential therapeutic applications. Sirolimus 115-124 mechanistic target of rapamycin kinase Homo sapiens 91-95 27789294-7 2016 By induction of autophagy via inhibition of mTOR using rapamycin an increase of ferritin H turnover was obtained in senescent cells, demonstrating a mTOR dependent reduction of autophagy in senescent human fibroblasts. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 44-48 27789294-7 2016 By induction of autophagy via inhibition of mTOR using rapamycin an increase of ferritin H turnover was obtained in senescent cells, demonstrating a mTOR dependent reduction of autophagy in senescent human fibroblasts. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 149-153 28529994-4 2016 Rapamycin, a potent inhibitor of mTOR (mammalian target of rapamycin), has been demonstrated to be a potential pharmacological agent against the aberrant mTOR signaling seen in ciliopathies such as polycystic kidney disease (PKD) and tuberous sclerosis complex (TSC). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 33-37 28529994-4 2016 Rapamycin, a potent inhibitor of mTOR (mammalian target of rapamycin), has been demonstrated to be a potential pharmacological agent against the aberrant mTOR signaling seen in ciliopathies such as polycystic kidney disease (PKD) and tuberous sclerosis complex (TSC). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 39-68 28529994-4 2016 Rapamycin, a potent inhibitor of mTOR (mammalian target of rapamycin), has been demonstrated to be a potential pharmacological agent against the aberrant mTOR signaling seen in ciliopathies such as polycystic kidney disease (PKD) and tuberous sclerosis complex (TSC). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 154-158 27371338-1 2016 We previously demonstrated that rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), protects against N-methyl-d-aspartic acid (NMDA)-induced retinal damage in rats. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 63-92 27371338-1 2016 We previously demonstrated that rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), protects against N-methyl-d-aspartic acid (NMDA)-induced retinal damage in rats. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 94-98 26276683-5 2016 RESULTS: The mTOR inhibitor rapamycin was found to be a potent inhibitor for HCV RNA replication in Huh-7.5 cells as well as primary human hepatocytes. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 13-17 27691052-3 2016 Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been reported to obviate the need for pancreatectomy, but experience is limited. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 44-48 27916907-8 2016 In addition, the anti-EMT effects of metformin could be partially in accord with rapamycin, a specific mTOR inhibitor. Sirolimus 81-90 mechanistic target of rapamycin kinase Homo sapiens 103-107 27495747-1 2016 The mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus are increasingly used in cardiothoracic transplantation. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 4-33 27495747-1 2016 The mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus are increasingly used in cardiothoracic transplantation. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 35-39 27599716-10 2016 Inhibition of autophagic clearance of Abeta led to increased ROS levels and aggravating mitochondrial defects, which were blocked by Rapamycin (an mTOR inhibitor). Sirolimus 133-142 mechanistic target of rapamycin kinase Homo sapiens 147-151 27463007-8 2016 Notably, rapamycin rescued oxidative stress-induced embryonic defects via modulating gene expression of sirtuin and mammalian target of rapamycin. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 116-145 28124643-11 2016 Rapamycin also attenuated the TGF beta 1 induced activation of PI3K and mTOR, and its inhibitory effects were similar to those of mTOR silencing and a specific PI3K inhibitor. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 72-76 26952863-2 2016 Recently, this signalling pathway has come to the attention of the scientific community owing to the unexpected finding that inhibition of mTOR by rapamycin, an antibiotic with immunosuppressant and chemotherapeutic properties, extends lifespan in diverse animal models. Sirolimus 147-156 mechanistic target of rapamycin kinase Homo sapiens 139-143 27245261-2 2016 More recently mTOR inhibitors such as sirolimus and everolimus have been introduced to the field of allogeneic haematopoietic stem cell transplantation where their unique combination of immunosuppressive purposes offering reduced nephrotoxicity and potential antimalignant effects reflect a unique drug profile that has led to their widespread use in both prophylaxis and therapy of graft-versus-host disease (GVHD). Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 14-18 27589687-0 2016 Phase I dose-escalation study of the mTOR inhibitor sirolimus and the HDAC inhibitor vorinostat in patients with advanced malignancy. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 37-41 27256566-3 2016 Here, we showed that suppressing mTOR signaling in in vitro-expanded Vgamma4 gammadelta T cells via the mechanistic inhibitor rapamycin enhanced their cytotoxicity against multiple tumor cell lines, and these cells performed better tumor-suppressing effects upon adoptive therapy. Sirolimus 126-135 mechanistic target of rapamycin kinase Homo sapiens 33-37 27735842-8 2016 Additionally, DOXO significantly induced mTOR expression in hCPCs, and inhibition of mTOR signaling by rapamycin, a specific inhibitor, rescued DOXO-mediated autophagosome depletion in hCPCs with significant reduction of DOXO-mediated cytosolic Ca2+ accumulation in hCPCs, and restored SMP30 and mTOR expression. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 85-89 27616194-1 2016 Rapamycin, a specific inhibitor of mTOR used extensively as an immunosuppressant, has been expanded recently to cancer therapy, because the mTOR signal is known to be up-regulated in various cancer cells including hepatocellular carcinoma (HCC) cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 35-39 27616194-1 2016 Rapamycin, a specific inhibitor of mTOR used extensively as an immunosuppressant, has been expanded recently to cancer therapy, because the mTOR signal is known to be up-regulated in various cancer cells including hepatocellular carcinoma (HCC) cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 140-144 27616194-11 2016 Overall, this study demonstrates that rapamycin inhibited the proliferation of Huh7 cells by up-regulating the expression of p53 and down-regulating the ERK1/2 signal, indicating that p53 is a useful biomarker for anti-cancer therapy using the specific inhibitor of mTOR signal, rapamycin, against hepatocellular carcinoma cells. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 266-270 27616194-11 2016 Overall, this study demonstrates that rapamycin inhibited the proliferation of Huh7 cells by up-regulating the expression of p53 and down-regulating the ERK1/2 signal, indicating that p53 is a useful biomarker for anti-cancer therapy using the specific inhibitor of mTOR signal, rapamycin, against hepatocellular carcinoma cells. Sirolimus 279-288 mechanistic target of rapamycin kinase Homo sapiens 266-270 27735842-8 2016 Additionally, DOXO significantly induced mTOR expression in hCPCs, and inhibition of mTOR signaling by rapamycin, a specific inhibitor, rescued DOXO-mediated autophagosome depletion in hCPCs with significant reduction of DOXO-mediated cytosolic Ca2+ accumulation in hCPCs, and restored SMP30 and mTOR expression. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 85-89 27705797-3 2016 Here, we show that simultaneous inhibition of mTOR signaling to both S6K1 and 4E-BP1 is sufficient to reduce AKT-induced muscle growth and render it insensitive to the mTORC1-inhibitor rapamycin. Sirolimus 185-194 mechanistic target of rapamycin kinase Homo sapiens 46-50 27423526-1 2016 BACKGROUND: The purpose of the study was to evaluate lipid homeostasis before and after treatment of everolimus, the mammalian target of the rapamycin (mTOR) inhibitor, among patients with tuberous sclerosis complex (TSC). Sirolimus 141-150 mechanistic target of rapamycin kinase Homo sapiens 152-156 27581648-4 2016 First, inhibition of translation with cycloheximide had a more potent effect on protein synthesis than rapamycin indicating that mTOR function during hypertrophy is not on general, but rather on specific protein synthesis. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 129-133 27581648-8 2016 Inhibition of mTOR signaling by rapamycin disrupted mTOR-rDNA promoter interaction and resulted in altered histone marks indicative of repressed transcription and formation of higher-order chromatin structure. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 14-18 27581648-8 2016 Inhibition of mTOR signaling by rapamycin disrupted mTOR-rDNA promoter interaction and resulted in altered histone marks indicative of repressed transcription and formation of higher-order chromatin structure. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 52-56 27484210-2 2016 We further hypothesized that co-treatment of CDK inhibitors with rapamycin, an mTOR inhibitor, would be an effective combinatory strategy for the inhibition of prostate cancer regard to androgen receptor (AR) status due to inhibition of proliferative pathway, PI3K/AKT/mTOR, and induction of cell death mechanisms. Sirolimus 65-74 mechanistic target of rapamycin kinase Homo sapiens 79-83 27484210-2 2016 We further hypothesized that co-treatment of CDK inhibitors with rapamycin, an mTOR inhibitor, would be an effective combinatory strategy for the inhibition of prostate cancer regard to androgen receptor (AR) status due to inhibition of proliferative pathway, PI3K/AKT/mTOR, and induction of cell death mechanisms. Sirolimus 65-74 mechanistic target of rapamycin kinase Homo sapiens 269-273 27371614-3 2016 Rapamycin is a well-characterized inhibitor of mTOR complex 1 signalling and a potent inducer of Treg cells in the periphery. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 47-51 27742384-3 2016 Mammalian target of rapamycin inhibitors, both sirolimus and everolimus, have been studied in several trials to facilitate preservation of kidney function with variable effects on kidney allograft function and immunogenicity. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 0-29 26604019-6 2016 mTOR inhibitors such as sirolimus or everolimus have shown a beneficial effect on the decline in pulmonary function and a reduction of angiomyolipoma size, but are necessary in only some patients. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 0-4 27310200-1 2016 BACKGROUND: Sirolimus is a mammalian target of rapamycin inhibitor that is being used to prevent organ rejection in kidney transplant patients often in combination with calcineurin inhibitors (CNIs; cyclosporine and tacrolimus). Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 27-56 27694325-2 2016 Rapamycin is an inhibitor of the serine/threonine kinase mammalian target of rapamycin (mTOR) implicated in the progression of many different forms of renal disease. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 57-86 27694325-2 2016 Rapamycin is an inhibitor of the serine/threonine kinase mammalian target of rapamycin (mTOR) implicated in the progression of many different forms of renal disease. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 88-92 27694325-3 2016 Given that Na/K-ATPase signaling is known to stimulate the mTOR system, we speculated that the ameliorative effects of rapamycin might influence this pathway. Sirolimus 119-128 mechanistic target of rapamycin kinase Homo sapiens 59-63 27694325-10 2016 Our results suggest that rapamycin may have a dual effect on cardiac fibrosis through (1) mTOR inhibition and (2) inhibiting MBG-mediated profibrotic signaling and provide support for beneficial effect of a novel therapy for uremic cardiomyopathy. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 90-94 27658964-10 2016 Importantly, rapamycin, a well-known mTOR inhibitor, is able to reduce STAT3 phosphorylation to basal levels in our experimental model. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 37-41 27392709-10 2016 Both PI3K inhibitor LY294002 and mTOR inhibitor rapamycin decreased the augmented caspase-3 expression and TC content induced by ox-LDL, respectively. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 33-37 27163752-4 2016 Using a formalin-induced conditioned place avoidance (F-CPA) test, the current study investigated the effects of the mTOR specific inhibitor rapamycin on noxious stimulation induced aversion in the rostral anterior cingulate cortex (rACC). Sirolimus 141-150 mechanistic target of rapamycin kinase Homo sapiens 117-121 27188418-7 2016 Rapamycin (50 nM; an inhibitor of mTOR) attenuated (P < 0.05) the stimulatory effect of AKG on mTOR signaling and syntheses of milk protein and lactose, while relieving (P < 0.05) an inhibitory effect of AKG on expression of proteins related to ERS. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 34-38 27188418-7 2016 Rapamycin (50 nM; an inhibitor of mTOR) attenuated (P < 0.05) the stimulatory effect of AKG on mTOR signaling and syntheses of milk protein and lactose, while relieving (P < 0.05) an inhibitory effect of AKG on expression of proteins related to ERS. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 98-102 27482884-0 2016 Mechanistically distinct cancer-associated mTOR activation clusters predict sensitivity to rapamycin. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 43-47 27593484-4 2016 Such decreased pro-IL-1beta expression in TSC1 KO macrophages was rescued by reducing mTORC1 activity with rapamycin or deletion of mTOR. Sirolimus 107-116 mechanistic target of rapamycin kinase Homo sapiens 86-90 27482884-8 2016 Moreover, VHL-deficient cells that expressed activating mTOR mutants grew tumors that were sensitive to rapamycin treatment. Sirolimus 104-113 mechanistic target of rapamycin kinase Homo sapiens 56-60 27610411-1 2016 Mammalian target of rapamycin (mTOR) signaling is a core pathway in cellular metabolism, and control of the mTOR pathway by rapamycin shows potential for the treatment of metabolic diseases. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 31-35 27566410-9 2016 Expression of both constitutive and immunoproteasome subunits in FCD II-derived astroglial cultures was negatively regulated by treatment with the immunomodulatory drug rapamycin (inhibitor of the mammalian target of rapamycin (mTOR) pathway, which is activated in both TSC and FCD II). Sirolimus 169-178 mechanistic target of rapamycin kinase Homo sapiens 197-226 27566410-9 2016 Expression of both constitutive and immunoproteasome subunits in FCD II-derived astroglial cultures was negatively regulated by treatment with the immunomodulatory drug rapamycin (inhibitor of the mammalian target of rapamycin (mTOR) pathway, which is activated in both TSC and FCD II). Sirolimus 169-178 mechanistic target of rapamycin kinase Homo sapiens 228-232 27635236-4 2016 However, progress in using inhibitors of mTOR signaling as therapeutic agents in oncology has been limited by a number of factors, including the fact that the classic mTOR inhibitor, rapamycin, inhibits only some of the effects of mTOR; the existence of several feedback loops; and the crucial importance of mTOR in normal physiology. Sirolimus 183-192 mechanistic target of rapamycin kinase Homo sapiens 41-45 27635236-4 2016 However, progress in using inhibitors of mTOR signaling as therapeutic agents in oncology has been limited by a number of factors, including the fact that the classic mTOR inhibitor, rapamycin, inhibits only some of the effects of mTOR; the existence of several feedback loops; and the crucial importance of mTOR in normal physiology. Sirolimus 183-192 mechanistic target of rapamycin kinase Homo sapiens 167-171 27635236-4 2016 However, progress in using inhibitors of mTOR signaling as therapeutic agents in oncology has been limited by a number of factors, including the fact that the classic mTOR inhibitor, rapamycin, inhibits only some of the effects of mTOR; the existence of several feedback loops; and the crucial importance of mTOR in normal physiology. Sirolimus 183-192 mechanistic target of rapamycin kinase Homo sapiens 167-171 27635236-4 2016 However, progress in using inhibitors of mTOR signaling as therapeutic agents in oncology has been limited by a number of factors, including the fact that the classic mTOR inhibitor, rapamycin, inhibits only some of the effects of mTOR; the existence of several feedback loops; and the crucial importance of mTOR in normal physiology. Sirolimus 183-192 mechanistic target of rapamycin kinase Homo sapiens 167-171 27198515-5 2016 Brefeldin A, Akt inhibitor, Bay 11-7085 (an inhibitor of NF-kappaB activation), and rapamycin (mTOR inhibitor) inhibited the TNF-alpha-stimulated productions of inflammatory mediators, and activations of Akt, mTOR, and NF-kappaB in keratinocytes. Sirolimus 84-93 mechanistic target of rapamycin kinase Homo sapiens 95-99 27610411-1 2016 Mammalian target of rapamycin (mTOR) signaling is a core pathway in cellular metabolism, and control of the mTOR pathway by rapamycin shows potential for the treatment of metabolic diseases. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 108-112 27174915-9 2016 Testing their cooperation in vitro, a significant involvement of IDO1 in mTOR immunogenic pathway was found, able to counteract the aim of rapamycin treatment. Sirolimus 139-148 mechanistic target of rapamycin kinase Homo sapiens 73-77 27297394-4 2016 Utilizing Western blot analysis, we demonstrate that similar to rapamycin (a known mTOR inhibitor), mf downregulate the phosphorylation of mTOR and its regulatory proteins, p70S6K1 and 4E-BP1, a process essential for DC protein synthesis. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 83-87 27297394-4 2016 Utilizing Western blot analysis, we demonstrate that similar to rapamycin (a known mTOR inhibitor), mf downregulate the phosphorylation of mTOR and its regulatory proteins, p70S6K1 and 4E-BP1, a process essential for DC protein synthesis. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 139-143 28903328-8 2017 Rapamycin, an mTOR inhibitor, hinders cell proliferation along with sphere formation in vitro and impedes tumor growth in vivo. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 27418134-12 2016 MiR-184 based supplementary therapeutics and mTOR blocker, like rapamycin, are prospective options for AMD treatment. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 45-49 27601112-1 2016 Sirolimus is an inhibitor of the mammalian target of rapamycin (mTOR), used as an immunosuppressant for solid-organ transplant recipients and patients with autoimmune disorders. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 33-62 27221774-5 2016 Myricetin, Akt inhibitor, Bay 11-7085 (an inhibitor of NF-kappaB activation), rapamycin (mTOR inhibitor) and N-acetylcysteine attenuated TNF-alpha-induced activation of Akt, mTOR and NF-kappaB. Sirolimus 78-87 mechanistic target of rapamycin kinase Homo sapiens 89-93 27525306-6 2016 These effects mimicked that of c-Met inhibitor SU11274 or PI3 kinase inhibitor LY294002 or mTOR inhibitor rapamycin treatment. Sirolimus 106-115 mechanistic target of rapamycin kinase Homo sapiens 91-95 27601112-1 2016 Sirolimus is an inhibitor of the mammalian target of rapamycin (mTOR), used as an immunosuppressant for solid-organ transplant recipients and patients with autoimmune disorders. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 64-68 27019134-1 2016 Everolimus (EVR) is an orally-administered rapamycin analog that selectively inhibits the mammalian target of rapamycin (mTOR) kinase (mainly mTORC1 and likely mTORC2) and the related signaling pathway. Sirolimus 43-52 mechanistic target of rapamycin kinase Homo sapiens 90-119 27630374-0 2016 The Effect of Different Dosing Schedules of Intravitreal Sirolimus, a Mammalian Target of Rapamycin (mTOR) Inhibitor, in the Treatment of Non-Infectious Uveitis (An American Ophthalmological Society Thesis). Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 70-99 27630374-0 2016 The Effect of Different Dosing Schedules of Intravitreal Sirolimus, a Mammalian Target of Rapamycin (mTOR) Inhibitor, in the Treatment of Non-Infectious Uveitis (An American Ophthalmological Society Thesis). Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 101-105 27630374-1 2016 PURPOSE: To determine if two different doses of intravitreal sirolimus, an mTOR inhibitor, can decrease inflammation and is safe in eyes with non-infectious posterior, intermediate, or panuveitis in the Sirolimus as a Therapeutic Approach UVEitis: Protocol-2 (SAVE-2) Study. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 75-79 27345368-5 2016 Notably, the mTOR inhibitor rapamycin, previously reported to mimic effects of CR, abolishes this expansion of ISCs. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 13-17 26991755-9 2016 The PI3K inhibitor wortmannin and the mTOR inhibitor rapamycin inhibited APR-246-induced nuclear translocation of NFE2L2 and counteracted the protective cellular responses to APR-246, resulting in synergistic cell killing together with APR-246. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 38-42 27208895-3 2016 mTOR forms two different protein complexes, mTORC1 and mTORC2; the former is acutely sensitive to rapamycin whereas the latter is only chronically sensitive to rapamycin in vivo. Sirolimus 98-107 mechanistic target of rapamycin kinase Homo sapiens 0-4 27208895-3 2016 mTOR forms two different protein complexes, mTORC1 and mTORC2; the former is acutely sensitive to rapamycin whereas the latter is only chronically sensitive to rapamycin in vivo. Sirolimus 160-169 mechanistic target of rapamycin kinase Homo sapiens 0-4 27648364-6 2016 Rapamycin (Sirolimus) is an mTORC1 inhibitor, which inhibits the PI3K/Akt/mTOR signaling pathway, which is commonly altered in prostate cancer. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 28-32 27648364-6 2016 Rapamycin (Sirolimus) is an mTORC1 inhibitor, which inhibits the PI3K/Akt/mTOR signaling pathway, which is commonly altered in prostate cancer. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 28-32 27648364-7 2016 We determined the expression of cyclin D1 and phosphorylated-mTOR proteins in association with the response to rapamycin in two androgen sensitive (22RV1 and LNCaP) and two androgen independent (DU145 and PC3) prostate cancer cell lines and found that the base-line and changes of cyclin D1 level, but not the expression level of p-mTOR, correlated with rapamycin sensitivity. Sirolimus 111-120 mechanistic target of rapamycin kinase Homo sapiens 61-65 27394642-8 2016 Inhibition of mTOR pathway using rapamycin rescued the aberrant differentiation. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 14-18 27329724-8 2016 Further, three other cell lines established independently from the tumors of three patients with HCC were also approximately 2,000-fold times more sensitive to rapamycin, which correlated closely with the inhibition of mTOR Ser2481 phosphorylation by rapamycin. Sirolimus 160-169 mechanistic target of rapamycin kinase Homo sapiens 219-223 27329724-8 2016 Further, three other cell lines established independently from the tumors of three patients with HCC were also approximately 2,000-fold times more sensitive to rapamycin, which correlated closely with the inhibition of mTOR Ser2481 phosphorylation by rapamycin. Sirolimus 251-260 mechanistic target of rapamycin kinase Homo sapiens 219-223 27493626-6 2016 This was reversed dose-dependently by administering the mTOR inhibitor rapamycin. Sirolimus 71-80 mechanistic target of rapamycin kinase Homo sapiens 56-60 26538632-7 2016 Kim-1 expression led to activation of the mammalian target of rapamycin (mTOR) pathway, and inhibition of this pathway with rapamycin increased survival. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 73-77 27019134-1 2016 Everolimus (EVR) is an orally-administered rapamycin analog that selectively inhibits the mammalian target of rapamycin (mTOR) kinase (mainly mTORC1 and likely mTORC2) and the related signaling pathway. Sirolimus 43-52 mechanistic target of rapamycin kinase Homo sapiens 121-125 30634218-1 2016 OBJECTIVE: To explore the mechanism of electropuncture (EA) for reducing diet-induced obesity (DIO) rat weight through tuberous sclerosis complex 1 (TSC1 )-mammalian target of rapa- mycin (mTOR) signal pathway in hypothalamus. Sirolimus 176-187 mechanistic target of rapamycin kinase Homo sapiens 189-193 26526985-3 2016 It is associated with the mutation of two genes: TSC1 (hamartin) and TSC2 (tuberin), with the change in the functionality of the complex target of rapamycin (mTOR). Sirolimus 147-156 mechanistic target of rapamycin kinase Homo sapiens 158-162 27030639-0 2016 Combination targeted therapy of VEGFR inhibitor, sorafenib, with an mTOR inhibitor, sirolimus induced a remakable response of rapid progressive Uterine PEComa. Sirolimus 84-93 mechanistic target of rapamycin kinase Homo sapiens 68-72 27338360-1 2016 The first compound that inhibited the mammalian target of rapamycin (mTOR), sirolimus (rapamycin) was discovered in the 1970s as a soil bacterium metabolite collected on Easter Island (Rapa Nui). Sirolimus 76-85 mechanistic target of rapamycin kinase Homo sapiens 38-67 27338360-1 2016 The first compound that inhibited the mammalian target of rapamycin (mTOR), sirolimus (rapamycin) was discovered in the 1970s as a soil bacterium metabolite collected on Easter Island (Rapa Nui). Sirolimus 76-85 mechanistic target of rapamycin kinase Homo sapiens 69-73 27338360-1 2016 The first compound that inhibited the mammalian target of rapamycin (mTOR), sirolimus (rapamycin) was discovered in the 1970s as a soil bacterium metabolite collected on Easter Island (Rapa Nui). Sirolimus 58-67 mechanistic target of rapamycin kinase Homo sapiens 69-73 27045863-0 2016 Huaier aqueous extract sensitizes cells to rapamycin and cisplatin through activating mTOR signaling. Sirolimus 43-52 mechanistic target of rapamycin kinase Homo sapiens 86-90 27045863-9 2016 Moreover, activation of mTOR signaling induced by Huaier contributes to the increased sensitivity of cells to rapamycin or cisplatin in response to Huaier treatment. Sirolimus 110-119 mechanistic target of rapamycin kinase Homo sapiens 24-28 27296621-10 2016 The efficacy of PKC inhibitor (GF 109203X) or mTOR complex 1 inhibitor (rapamycin) for attenuating mechanical hyperalgesia and mechanical allodynia by intraplantar injection was dose-dependent. Sirolimus 72-81 mechanistic target of rapamycin kinase Homo sapiens 46-50 28123821-8 2016 Also, we showed that blocking spinal mTOR by intrathecal injection of rapamycin significantly inhibited pain responses induced by mechanical and thermal stimulation. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 37-41 27167192-6 2016 Treatment with mTOR pathway inhibitor rapamycin further verified its contribution to HCC progression in AIM2 absent HCC cells. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 15-19 27256228-1 2016 OBJECTIVE: To assess the efficacy and safety of mammalian target of rapamycin (mTOR) inhibitor rapamycin in treatment of children with cardiac rhabdomyoma, associated with tuberous sclerosis complex (TSC). Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 79-83 27150260-1 2016 Rapamycin, a potent antifungal antibiotic, was approved as immunosuppressant, and lately its derivatives have been developed into mTOR targeting anticancer drugs. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 130-134 26799240-10 2016 Among the mammalian target of rapamycin (mTOR) inhibitors, sirolimus was approved in 2002, and its use increased to 8.7% in 2009. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 10-39 27103123-1 2016 PURPOSE: Sirolimus, an oral mTOR inhibitor, may complement the anti-angiogenic and anti-tumor activity of sunitinib, an oral small molecule inhibitor of multiple receptor tyrosine kinases, by vertical disruption of vascular epithelial growth factor receptor (VEGFR) signaling, by reducing the compensatory production of VEGF in sunitinib-treated patients and also by directly inhibiting tumor cell proliferation. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 28-32 26799240-10 2016 Among the mammalian target of rapamycin (mTOR) inhibitors, sirolimus was approved in 2002, and its use increased to 8.7% in 2009. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 41-45 27132889-5 2016 Mechanistically, small interfering RNA knockdown of RAPTOR, a component of mTOR complex 1, phenocopied the mesendoderm-enhancing effects of rapamycin. Sirolimus 140-149 mechanistic target of rapamycin kinase Homo sapiens 75-79 27109477-5 2016 Overexpression of FXR prevented the growth of cells and induced cell cycle arrest, which was enhanced by the mTOR/S6K inhibitor rapamycin. Sirolimus 128-137 mechanistic target of rapamycin kinase Homo sapiens 109-113 27216612-3 2016 Recent studies have suggested that mTOR inhibitors such as rapamycin can reverse TSC-associated deficits in rodent models of TSC. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 35-39 27050906-5 2016 We show that Npm1 gene expression is dependent on mTOR as demonstrated by treatment of wild-type and Pten inactivated MEFs cultured with rapamycin or by transient transfections of small interfering RNA directed against mTOR. Sirolimus 137-146 mechanistic target of rapamycin kinase Homo sapiens 50-54 27196739-11 2016 The combination of ICG-001 and mTOR inhibitor, rapamycin, yielded an additive effect on the inhibition of viability in TamR cells. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 31-35 26348114-7 2016 RESULTS: In vitro western blot analysis showed that there were lower levels of expression of phosphorylated mammalian target of rapamycin, p70S6K and p4EBP1, transforming growth factor-beta and pSmad3 expression in the cells treated with sirolimus, MMF and sirolimus plus MMF. Sirolimus 238-247 mechanistic target of rapamycin kinase Homo sapiens 108-137 27009856-7 2016 Immunoprecipitation assay further revealed that KPNA2 physically associated with the phospho-mTOR/mTOR and this association was abolished by rapamycin treatment. Sirolimus 141-150 mechanistic target of rapamycin kinase Homo sapiens 93-97 27009856-7 2016 Immunoprecipitation assay further revealed that KPNA2 physically associated with the phospho-mTOR/mTOR and this association was abolished by rapamycin treatment. Sirolimus 141-150 mechanistic target of rapamycin kinase Homo sapiens 98-102 26607948-6 2016 Sirolimus was the most frequent mTOR inhibitor used (98.8%, n = 83). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 32-36 27048648-0 2016 Rapamycin reverses the senescent phenotype and improves immunoregulation of mesenchymal stem cells from MRL/lpr mice and systemic lupus erythematosus patients through inhibition of the mTOR signaling pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 185-189 27037216-3 2016 This study was performed to investigate how pre-inhibition of the mTOR pathway with rapamycin would affect BBB disruption and the size of the infarcted cortical area in the early stage of focal cerebral ischemia-reperfusion using quantitative analysis of BBB disruption. Sirolimus 84-93 mechanistic target of rapamycin kinase Homo sapiens 66-70 27037216-10 2016 Our data suggest that activation of mTOR pathway is necessary for neuronal survival in the early stage of cerebral ischemia-perfusion and that the reason for the enlarged cortical infarct by rapamycin pretreatment may be related to its non-BBB effects on the mTOR pathway. Sirolimus 191-200 mechanistic target of rapamycin kinase Homo sapiens 36-40 27037216-10 2016 Our data suggest that activation of mTOR pathway is necessary for neuronal survival in the early stage of cerebral ischemia-perfusion and that the reason for the enlarged cortical infarct by rapamycin pretreatment may be related to its non-BBB effects on the mTOR pathway. Sirolimus 191-200 mechanistic target of rapamycin kinase Homo sapiens 259-263 26348114-7 2016 RESULTS: In vitro western blot analysis showed that there were lower levels of expression of phosphorylated mammalian target of rapamycin, p70S6K and p4EBP1, transforming growth factor-beta and pSmad3 expression in the cells treated with sirolimus, MMF and sirolimus plus MMF. Sirolimus 257-266 mechanistic target of rapamycin kinase Homo sapiens 108-137 26886375-3 2016 We report an 18-year-old male with Gorham-Stout disease manifested by lytic rib lesions and an intractable pleural effusion that responded dramatically to the combination of the mammalian target of rapamycin (mTOR) inhibitor sirolimus and the aminobisphosphonate zoledronic acid after failing interferon therapy. Sirolimus 225-234 mechanistic target of rapamycin kinase Homo sapiens 178-207 30044067-8 2016 Conclusions: Rapamycin could inhibit the proliferation of keloid fibroblasts, and could not affect the apoptosis of cells.However, rapamycin induced the autophagy of keloid fibroblasts through regulating the expression of autophagy-related non-coding RNAs and genes in the mTOR signaling pathway. Sirolimus 131-140 mechanistic target of rapamycin kinase Homo sapiens 273-277 27029073-4 2016 To overcome this problem, CH12 was combined with the mTOR inhibitor rapamycin, leading to a synergistic inhibitory effect on EGFRvIII+PTEN- GBM in vivo. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 53-57 27029073-5 2016 Mechanistically, the synergistic antitumor effect was achieved via attenuating EGFR and PI3K/AKT/mTOR pathway more effectively and reversing the STAT5 activation caused by rapamycin treatment. Sirolimus 172-181 mechanistic target of rapamycin kinase Homo sapiens 97-101 26729448-2 2016 The mTOR inhibitor sirolimus has been used in the prevention and treatment of graft-versus-host disease (GVHD) after allogeneic haematopoietic stem cell transplantation (HSCT). Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 26927950-4 2016 However, pharmacological therapy with mTOR inhibitors such as everolimus and sirolimus is now emerging as an alternate approach. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 38-42 27090655-9 2016 Analyzing mechanism of action interference of the mTOR inhibitor sirolimus shows specific impact on the drug resistance signature imposed by cisplatin and paclitaxel, further holding evidence for a synthetic lethal interaction to paclitaxel mechanism of action involving cyclin D1. Sirolimus 65-74 mechanistic target of rapamycin kinase Homo sapiens 50-54 27070592-5 2016 In addition, suppression of mTOR activity by rapamycin decreased the level of activity of p70S6K, induced upregulation of p53 and caspase 3, and led to increase of apoptosis in K562R(IMT) cells. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 28-32 26879868-5 2016 We also found that a dominant negative mutant of Ras (Ras DN), a PI3K inhibitor (LY 294002), an Akt DN, and an mTOR inhibitor (rapamycin) attenuated ghrelin-caused colon cancer cell proliferation. Sirolimus 127-136 mechanistic target of rapamycin kinase Homo sapiens 111-115 26886375-3 2016 We report an 18-year-old male with Gorham-Stout disease manifested by lytic rib lesions and an intractable pleural effusion that responded dramatically to the combination of the mammalian target of rapamycin (mTOR) inhibitor sirolimus and the aminobisphosphonate zoledronic acid after failing interferon therapy. Sirolimus 225-234 mechanistic target of rapamycin kinase Homo sapiens 209-213 27020819-8 2016 The expression of P-p70S6K1 declined after rapamycin treatment, showing that the signaling pathway of mTOR is inhibited by rapamycin. Sirolimus 43-52 mechanistic target of rapamycin kinase Homo sapiens 102-106 27020819-8 2016 The expression of P-p70S6K1 declined after rapamycin treatment, showing that the signaling pathway of mTOR is inhibited by rapamycin. Sirolimus 123-132 mechanistic target of rapamycin kinase Homo sapiens 102-106 26626406-4 2016 Based on the evidence of mammalian target of rapamycin mTORC, mTOR Complex; RAS, Rat sarcoma; RAF, rapidly accelerated fibrosarcoma (mTOR) pathway activation in the tumor, targeted therapy was applied resulting in complete remission of disease. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 55-59 27000748-8 2016 However, the presenescent SMSCs can be rejuvenated by agents that stimulate autophagy, such as the mTOR inhibitor rapamycin. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 99-103 26698679-6 2016 Primary hSCs cultures were established from each biopsy and divided into a control group and one treated with rapamycin, the inhibitor of mTOR, for 24 hours. Sirolimus 110-119 mechanistic target of rapamycin kinase Homo sapiens 138-142 26977999-9 2016 Regarding monitoring of mTOR inhibitors (mTORis), the results of the first study that provided data on measurement of mTOR pathway molecules [p70 ribosomal protein S6 kinase (p70S6 kinase) and phosphorylated ribosomal protein S6] suggest that they are suitable targets for individualized PD monitoring of sirolimus and everolimus after organ transplantation. Sirolimus 305-314 mechanistic target of rapamycin kinase Homo sapiens 41-45 27008180-3 2016 mTOR inhibition by rapamycin significantly preserves neuronal ATP levels, particularly when oxidative phosphorylation is impaired, such as in neurons treated with mitochondrial inhibitors, or in neurons derived from maternally inherited Leigh syndrome (MILS) patient iPS cells with ATP synthase deficiency. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 0-4 26931735-2 2016 mTOR signalling is upregulated in PKD and rapamycin slows cyst expansion, whereas renal inactivation of the Tsc genes causes cysts. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 0-4 26639422-4 2016 Sirolimus impaired BKPyV replication with a 90% inhibitory concentration of 4 ng/mL by interfering with mTOR-SP6-kinase activation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 104-108 27011924-5 2016 But recently therapy with mammalian target of rapamycin (mTOR) inhibitors such as sirolimus has shown promising results in the stabilization of lung function and reduction of chylous effusions in LAM. Sirolimus 82-91 mechanistic target of rapamycin kinase Homo sapiens 26-55 27011924-5 2016 But recently therapy with mammalian target of rapamycin (mTOR) inhibitors such as sirolimus has shown promising results in the stabilization of lung function and reduction of chylous effusions in LAM. Sirolimus 82-91 mechanistic target of rapamycin kinase Homo sapiens 57-61 26748241-2 2016 Temsirolimus (TEM) and its primary active metabolite rapamycin allosterically block mTOR complex 1 substrate recruitment. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 84-88 27007909-5 2016 Additionally, in duck myoblasts treated with LY294002 and rapamycin, the specific inhibitors ofPI3K and mTOR, respectively, the overexpression of Six1 could significantly ameliorate inhibitive effects of these inhibitors on protein synthesis. Sirolimus 58-67 mechanistic target of rapamycin kinase Homo sapiens 104-108 26335579-10 2016 Surprisingly, rapamycin (an mTOR inhibitor), cAMP, and its natural inducer isoproterenol, elicit identical dephosphorylation kinetics on both S6K1 ribosomal kinase (a downstream mTOR target) and H3. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 28-32 26861999-5 2016 We applied the blockers of Kv1.3 (Anuroctoxin), KCa3.1 (TRAM-34) and CRAC (2-Apb) channels of T cells either alone or in combination with rapamycin, the inhibitor of the mammalian target of rapamycin (mTOR). Sirolimus 138-147 mechanistic target of rapamycin kinase Homo sapiens 170-199 26861999-5 2016 We applied the blockers of Kv1.3 (Anuroctoxin), KCa3.1 (TRAM-34) and CRAC (2-Apb) channels of T cells either alone or in combination with rapamycin, the inhibitor of the mammalian target of rapamycin (mTOR). Sirolimus 138-147 mechanistic target of rapamycin kinase Homo sapiens 201-205 26335579-10 2016 Surprisingly, rapamycin (an mTOR inhibitor), cAMP, and its natural inducer isoproterenol, elicit identical dephosphorylation kinetics on both S6K1 ribosomal kinase (a downstream mTOR target) and H3. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 178-182 26833095-2 2016 Immunosuppressive drug rapamycin (RPM), targeting on the key cellular metabolism molecule mTOR, is currently used in clinics to treat patients with allo-grafts, autoimmune diseases and tumors. Sirolimus 23-32 mechanistic target of rapamycin kinase Homo sapiens 90-94 27239444-0 2016 mTOR inhibition by rapamycin increases ceramide synthesis by promoting transforming growth factor-beta1/Smad signaling in the skin. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 0-4 26776341-6 2016 Rapamycin and PP242 inhibit phosphorylation of Akt, ribosomal S6 kinase, 4EBP1 and mTOR. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 83-87 26707081-2 2016 Mammalian target of rapamycin (mTOR) activation is one of the most frequent events in human malignancies, and is critical for sustaining the self-renewing ability of cancer stem cells (CSCs); inhibition by rapamycin is an effective and promising strategy in anticancer treatments. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 31-35 26707081-3 2016 In the present study, we found that mTOR activity was closely related to the self-renewal ability of BrCSCs, and in triple negative MDA-MB-453 and MDA-MB-468 cells, rapamycin repression of mTOR phosphorylation decreased the number of mammospheres and helped to sensitize the resistant CSCs to low-dose radiation therapy. Sirolimus 165-174 mechanistic target of rapamycin kinase Homo sapiens 36-40 26707081-3 2016 In the present study, we found that mTOR activity was closely related to the self-renewal ability of BrCSCs, and in triple negative MDA-MB-453 and MDA-MB-468 cells, rapamycin repression of mTOR phosphorylation decreased the number of mammospheres and helped to sensitize the resistant CSCs to low-dose radiation therapy. Sirolimus 165-174 mechanistic target of rapamycin kinase Homo sapiens 189-193 26713679-8 2016 Whilst the mTOR inhibitor rapamycin has shown some benefit in patients with LAM, with stabilisation of lung function and improved quality of life, cessation of treatment results in recurrence of the disease progression. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 11-15 26800397-6 2016 Blocking the activation of Akt with LY294002 or mTOR with rapamycin significantly prevented miR-222-induced proliferation and restored the sensitivity of bladder cancer cells to cisplatin. Sirolimus 58-67 mechanistic target of rapamycin kinase Homo sapiens 48-52 26916116-5 2016 First, different doses of rapamycin are needed to suppress mTOR in different cell lines; second, different doses of rapamycin are needed to suppress the phosphorylation of different mTOR substrates; and third, there is a differential sensitivity of the two mTOR complexes mTORC1 and mTORC2 to rapamycin. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 59-63 26916116-6 2016 Intriguingly, the enigmatic properties of rapamycin dosage can be explained in large part by the competition between rapamycin and phosphatidic acid (PA) for mTOR. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 158-162 26698023-9 2016 Rapamycin (which primarily inhibits mTORC1), ATP-competitive, dual mTORC1/mTORC2 inhibitors and upstream regulators of the mTOR pathway are being developed to treat autoimmune, hyperproliferative and degenerative diseases. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 36-40 26879559-6 2016 Inhibition of mTOR signaling with rapamycin, an mTOR signaling inhibitor, disturbed PGRN- or IL-6-mediated proliferation, migration and invasion of HCC cells in vitro. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 14-18 26879559-6 2016 Inhibition of mTOR signaling with rapamycin, an mTOR signaling inhibitor, disturbed PGRN- or IL-6-mediated proliferation, migration and invasion of HCC cells in vitro. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 48-52 26496029-8 2016 Remarkably, the latter feature coincided with a gain of sensitivity to the mTOR inhibitor rapamycin. Sirolimus 90-99 mechanistic target of rapamycin kinase Homo sapiens 75-79 26707081-4 2016 By inhibiting mTOR and mitochondrial manganese superoxide dismutase (MnSOD), we confirmed that rapamycin functioned through the mTOR/MnSOD/reactive oxygen species (ROS) signaling pathway, and the existence of Akt governed the rapamycin-induced asymmetric division (AD) of stem cells in cases of radiation-treated breast cancer. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 14-18 26707081-4 2016 By inhibiting mTOR and mitochondrial manganese superoxide dismutase (MnSOD), we confirmed that rapamycin functioned through the mTOR/MnSOD/reactive oxygen species (ROS) signaling pathway, and the existence of Akt governed the rapamycin-induced asymmetric division (AD) of stem cells in cases of radiation-treated breast cancer. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 128-132 26659860-3 2016 In syncytiotrophoblasts, starvation, rapamycin, or punicalagin all decreased the expression of phosphorylated ribosomal protein S6, a downstream target of the mTOR kinase, and of the autophagy markers, LC3-II and p62. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 159-163 26833095-2 2016 Immunosuppressive drug rapamycin (RPM), targeting on the key cellular metabolism molecule mTOR, is currently used in clinics to treat patients with allo-grafts, autoimmune diseases and tumors. Sirolimus 34-37 mechanistic target of rapamycin kinase Homo sapiens 90-94 26639426-7 2016 These findings suggest that acute inhibition of mTOR signaling by rapamycin induces an immediate impact on L5 pyramidal neurons" electrophysiological properties, indicating that its effects might involve mechanisms of ion channel"s regulation. Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 48-52 26607598-2 2016 There are several FDA-approved mTOR inhibitors (sirolimus, everolimus, and temsirolimus) with indications for cancer treatment and for prevention of solid organ rejection. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 31-35 26426522-7 2016 MEASUREMENTS AND MAIN RESULTS: mTOR activity was increased in peripheral blood mononuclear cells from patients with COPD, and treatment with rapamycin inhibited this as well as restoring corticosteroid sensitivity. Sirolimus 141-150 mechanistic target of rapamycin kinase Homo sapiens 31-35 26426522-9 2016 CONCLUSIONS: mTOR inhibition by rapamycin restores corticosteroid sensitivity via inhibition of c-Jun expression, and thus mTOR is a potential novel therapeutic target for COPD. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 13-17 26771918-3 2016 The mice were subsequently treated with rapamycin, a mammalian target of rapamycin (mTOR) inhibitor. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 53-82 26771918-3 2016 The mice were subsequently treated with rapamycin, a mammalian target of rapamycin (mTOR) inhibitor. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 84-88 27855235-3 2016 Sirolimus, an mTOR inhibitor, has reportedly been successful in treating children with severe diffuse HH, thus obviating the need for pancreatectomy. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 26620226-8 2016 The inhibitors LY294002 (PI3K-AKT inhibitor), U0126 (inhibitor of ERK1/2) and rapamycin (mTOR inhibitor) also blocked the ability of EGF to increase HIF-1alpha protein and to phosphorylate AKT, ERK1/2 and mTOR proteins. Sirolimus 78-87 mechanistic target of rapamycin kinase Homo sapiens 89-93 26563881-2 2016 mTORC1, consisting of mTOR, raptor, and mLST8 (GbetaL), is sensitive to rapamycin and thought to control autonomous cell growth in response to nutrient availability and growth factors. Sirolimus 72-81 mechanistic target of rapamycin kinase Homo sapiens 0-4 26752047-0 2016 Rapamycin Inhibits Oxidized Low Density Lipoprotein Uptake in Human Umbilical Vein Endothelial Cells via mTOR/NF-kappaB/LOX-1 Pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 105-109 26752047-6 2016 Western blotting showed that rapamycin inhibited mechanistic target of rapamycin (mTOR), p70s6k and IkappaBalpha phosphorylation triggered by ox-LDL. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 49-80 26752047-6 2016 Western blotting showed that rapamycin inhibited mechanistic target of rapamycin (mTOR), p70s6k and IkappaBalpha phosphorylation triggered by ox-LDL. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 82-86 26752047-8 2016 Moreover, immunofluorescent staining showed that rapamycin reduced the accumulation of p65 in the nucleus after ox-LDL treatment for 30 h. mTOR knockdown decreased LOX-1 protein production and IkappaBalpha phosphorylation induced by ox-LDL. Sirolimus 49-58 mechanistic target of rapamycin kinase Homo sapiens 139-143 26752047-10 2016 CONCLUSIONS: These findings demonstrate that rapamycin reduce mTOR phosphorylation and subsequently inhibit NF-kappaB activation and suppresses LOX-1, resulting in a reduction in ox-LDL uptake in HUVECs. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 62-66 26427479-3 2016 Rapamycin, an allosteric mTOR inhibitor, has been shown to block only one of the primary downstream mTOR effectors, p70 S6 kinase 1, in many cell types. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 25-29 26427479-3 2016 Rapamycin, an allosteric mTOR inhibitor, has been shown to block only one of the primary downstream mTOR effectors, p70 S6 kinase 1, in many cell types. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 100-104 26687832-5 2016 The interactions of calcineurin inhibitors and mammalian target of rapamycin inhibitor sirolimus also promote hypertension. Sirolimus 87-96 mechanistic target of rapamycin kinase Homo sapiens 47-76 26691741-2 2016 In the accompanying contrast-enhanced magnetic resonance imaging (CE-MRI) study we showed that the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduced BBB leakage and seizure activity during the chronic epileptic phase. Sirolimus 119-128 mechanistic target of rapamycin kinase Homo sapiens 130-134 26863215-7 2016 To avoid a subtotal pancreatectomy, an mTOR inhibitor - sirolimus - was introduced. Sirolimus 56-65 mechanistic target of rapamycin kinase Homo sapiens 39-43 26667069-1 2016 INTRODUCTION: Mammalian target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) are a class of immunosuppressive drugs approved for solid organ transplantation (SOT). Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 14-43 26667069-1 2016 INTRODUCTION: Mammalian target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) are a class of immunosuppressive drugs approved for solid organ transplantation (SOT). Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 45-49 27833825-8 2016 mTOR inhibitors, (e.g., sirolimus) are effective in stabilizing lung function, and reducing the size of chylous effusions, lymphangioleiomyomas, and angiomyolipomas. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 0-4 27883166-1 2016 Rapamycin, an mTOR inhibitor affects senescence through suppression of senescence-associated secretory phenotype (SASP). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 26530936-3 2016 The aim of this study was to examine the effects of rapamycin, an mTOR inhibitor, on MG63 osteosarcoma cells. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 66-70 26530936-7 2016 We found that rapamycin inhibited cell proliferation and decreased the phosphorylation of mTOR pathway components in MG63 cells. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 90-94 26427711-4 2016 The mTOR inhibitor rapamycin dose-dependently reduced the cell viability of the breast cancer cell line, MCF-7, but did not reduce the cell viability of the colon cancer cell line, HT-29. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 26462881-8 2016 An increase in the level of HDAC10 was also obtained when mTOR was inhibited by Rapamycin. Sirolimus 80-89 mechanistic target of rapamycin kinase Homo sapiens 58-62 25715851-8 2016 These analyses revealed that both TBTO and the mTOR inhibitor rapamycin inactivate RPS6, but via different mechanisms. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 47-51 27595116-1 2016 It has been demonstrated that mTOR/p70S6K pathway was abnormally activated in many cancers and rapamycin and its analogs can restrain tumor growth through inhibiting this pathway, but some tumors including esophageal squamous cell carcinoma (ESCC) appear to be insensitive to rapamycin in recent studies. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 30-34 26471831-5 2016 RESULTS: mTOR inhibitors AZD8055, RAD-001, rapamycin and BEZ235 induced synergistic cytotoxicity with the Chk1 inhibitor V158411 in p53 mutant colon cancer cells. Sirolimus 43-52 mechanistic target of rapamycin kinase Homo sapiens 9-13 27565326-1 2016 The presented study aimed to investigate the antitumor efficacy of combination of oxaliplatin with rapamycin, an mTOR inhibitor, in hepatocellular carcinoma (HCC). Sirolimus 99-108 mechanistic target of rapamycin kinase Homo sapiens 113-117 27421126-6 2016 Partial response of TSC-associated tumors and decrease the rate of lung function decline in females with LAM due to inhibition of mTOR pathway with sirolimus have been demonstrated. Sirolimus 148-157 mechanistic target of rapamycin kinase Homo sapiens 130-134 27504842-3 2016 This review discusses data regarding patient outcomes that were used to develop current guidelines for embolization of renal angiomyolipomas and presents recent data on 2 available mTOR inhibitors - sirolimus and everolimus - in the treatment of angiomyolipoma. Sirolimus 199-208 mechanistic target of rapamycin kinase Homo sapiens 181-185 32262937-6 2015 Moreover, we use rapamycin, the inhibitor of the mammalian target of rapamycin (mTOR), to induce autophagy and inhibit cell growth. Sirolimus 17-26 mechanistic target of rapamycin kinase Homo sapiens 49-78 26636543-2 2015 Here we studied the role of mTOR-dependent autophagy in implementating the antiprolifrative effect of mTORC1-specific inhibitor rapamycin and ATP-competitive mTOR kinase inhibitor pp242. Sirolimus 128-137 mechanistic target of rapamycin kinase Homo sapiens 28-32 26636543-2 2015 Here we studied the role of mTOR-dependent autophagy in implementating the antiprolifrative effect of mTORC1-specific inhibitor rapamycin and ATP-competitive mTOR kinase inhibitor pp242. Sirolimus 128-137 mechanistic target of rapamycin kinase Homo sapiens 102-106 32262937-6 2015 Moreover, we use rapamycin, the inhibitor of the mammalian target of rapamycin (mTOR), to induce autophagy and inhibit cell growth. Sirolimus 17-26 mechanistic target of rapamycin kinase Homo sapiens 80-84 26256674-1 2015 AIMS: Sirolimus is an mTOR inhibitor metabolized by CYP3A4 and CYP3A5. Sirolimus 6-15 mechanistic target of rapamycin kinase Homo sapiens 22-26 26566676-7 2015 Akt-mediated downregulation of Mfn2 was via the mTORC1 pathway because this downregulation was blocked by rapamycin, and overexpression of wild-type, but not kinase-dead mTOR, caused Mfn2 downregulation. Sirolimus 106-115 mechanistic target of rapamycin kinase Homo sapiens 48-52 26652716-8 2015 By treatment of MKN45 gastric cancer cells with rapamycin, a reduction of p-mTOR in the Western blot was achieved; however, expression of MMPs remained unaffected. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 76-80 26490657-6 2015 These effects were observed with as little as 0.5 nM rapamycin, demonstrating the profound affinity the compound has for FK-binding protein 12 (FKBP12), which subsequently forms the FKBP12/rapamycin complex to inhibit mTOR. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 218-222 26118661-6 2015 Furthermore, expression of a rapamycin-resistant and kinase-active mTOR (mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR-T (mTOR-TE), conferred resistance to rapamycin"s effects on PP2A, Erk1/2 and B-cell proliferation/viability, implying mTOR-dependent mechanism involved. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 73-77 26118661-7 2015 The findings indicate that rapamycin inhibits BAFF-stimulated cell proliferation/survival by targeting mTOR-mediated PP2A-Erk1/2 signaling pathway in normal and neoplastic B-lymphoid cells. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 103-107 26118661-0 2015 Rapamycin inhibits BAFF-stimulated cell proliferation and survival by suppressing mTOR-mediated PP2A-Erk1/2 signaling pathway in normal and neoplastic B-lymphoid cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 82-86 26118661-6 2015 Furthermore, expression of a rapamycin-resistant and kinase-active mTOR (mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR-T (mTOR-TE), conferred resistance to rapamycin"s effects on PP2A, Erk1/2 and B-cell proliferation/viability, implying mTOR-dependent mechanism involved. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 67-71 26118661-6 2015 Furthermore, expression of a rapamycin-resistant and kinase-active mTOR (mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR-T (mTOR-TE), conferred resistance to rapamycin"s effects on PP2A, Erk1/2 and B-cell proliferation/viability, implying mTOR-dependent mechanism involved. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 73-77 26118661-6 2015 Furthermore, expression of a rapamycin-resistant and kinase-active mTOR (mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR-T (mTOR-TE), conferred resistance to rapamycin"s effects on PP2A, Erk1/2 and B-cell proliferation/viability, implying mTOR-dependent mechanism involved. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 73-77 26118661-6 2015 Furthermore, expression of a rapamycin-resistant and kinase-active mTOR (mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR-T (mTOR-TE), conferred resistance to rapamycin"s effects on PP2A, Erk1/2 and B-cell proliferation/viability, implying mTOR-dependent mechanism involved. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 73-77 26549380-2 2015 Sirolimus, an inhibitor of mammalian target of rapamycin (mTOR), may inhibit growth of lymphatic malformations. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-56 26549380-2 2015 Sirolimus, an inhibitor of mammalian target of rapamycin (mTOR), may inhibit growth of lymphatic malformations. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 58-62 26496900-9 2015 These effects were enhanced following treatment with selected inhibitors of PI3K (LY294002), Akt (SH-6) and mTOR (rapamycin). Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 108-112 26588841-7 2015 Co-treatment with the antiprogestin mifepristone reduced graft growth (four independent donors, p<0.0001 two-sided t-test), as did treatment with the mTOR inhibitor rapamycin (three independent donors, p<0.0001 two-sided t-test). Sirolimus 168-177 mechanistic target of rapamycin kinase Homo sapiens 153-157 26289591-0 2015 Differentiating the mTOR inhibitors everolimus and sirolimus in the treatment of tuberous sclerosis complex. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 20-24 26289591-5 2015 The molecular connection between TSC and mTOR led to the clinical use of allosteric mTOR inhibitors (sirolimus and everolimus) for the treatment of TSC. Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 41-45 26289591-5 2015 The molecular connection between TSC and mTOR led to the clinical use of allosteric mTOR inhibitors (sirolimus and everolimus) for the treatment of TSC. Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 84-88 26289591-8 2015 Everolimus and sirolimus selectively inhibit mTOR signaling with similar molecular mechanisms, but with distinct clinical profiles. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 45-49 26284586-4 2015 We used an in vitro model to examine combination treatment with vemurafenib and mammalian target of rapamycin (mTOR) inhibitors, metformin and rapamycin. Sirolimus 100-109 mechanistic target of rapamycin kinase Homo sapiens 111-115 26569621-10 2015 Mice bearing advanced stage chemically-induced bladder tumours mimicking the histological and molecular nature of human tumours were then administrated with mTOR-pathway inhibitor sirolimus (rapamycin). Sirolimus 180-189 mechanistic target of rapamycin kinase Homo sapiens 157-161 26561782-11 2015 Whereas rapamycin augmented the A2E-mediated autophagy, attenuated protein expression of inflammation-associated and angiogenic factors, and blocked the Akt/mTOR pathway. Sirolimus 8-17 mechanistic target of rapamycin kinase Homo sapiens 157-161 26561782-12 2015 Taken together, A2E induces autophagy in RPE cells at the early stage of incubation, and this autophagic response can be inhibited by 3-MA or augmented by rapamycin via the mTOR pathway. Sirolimus 155-164 mechanistic target of rapamycin kinase Homo sapiens 173-177 26010766-6 2015 Rapamycin, an inhibitor of mTOR, can suppress the glucose-induced phosphorylation of HSF1/S326 and the expression of alpha B-crystallin. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 27606328-3 2015 Systemic pharmacological inhibition of mTOR signaling with rapamycin has been shown to rescue DISC1 deficiency-induced neurodevelopmental defects, as well as cognitive and affective deficits. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 39-43 26586952-1 2015 Mammalian target of rapamycin (mTOR) has been shown to be overactive in human colorectal cancer, but the first-generation mTOR inhibitor, rapamycin, has failed to show clinical efficacy against colorectal cancer. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 31-35 26540269-5 2015 Chronic systemic rapamycin treatment partially inhibited phosphorylation of a mechanistic target of rapamycin substrate in brain and stimulated LC3 cleavage, a marker of autophagic flux. Sirolimus 17-26 mechanistic target of rapamycin kinase Homo sapiens 78-109 26546739-5 2015 To evaluate a potential therapeutic option for the patient, we treated her primary skin fibroblasts and BM HSCs with the mTOR inhibitor rapamycin. Sirolimus 136-145 mechanistic target of rapamycin kinase Homo sapiens 121-125 26362858-0 2015 Rapamycin restores p14, p15 and p57 expression and inhibits the mTOR/p70S6K pathway in acute lymphoblastic leukemia cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 64-68 26644772-5 2015 Sirolimus causes immunosuppressive effects by inhibiting mammalian target of rapamycin (mTOR), and has well known side effects. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 57-86 26226122-4 2015 Introduction of sirolimus, an mTOR (mammalian target of rapamycin) inhibitor, obviated the requirement for glucose infusion. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 30-34 26226122-4 2015 Introduction of sirolimus, an mTOR (mammalian target of rapamycin) inhibitor, obviated the requirement for glucose infusion. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 36-65 26471225-3 2015 These findings open the possibility of disabling the pathological effects of senescence with mTOR inhibitors and may explain the anti-aging properties of rapamycin. Sirolimus 154-163 mechanistic target of rapamycin kinase Homo sapiens 93-97 26181590-7 2015 Further, the apoptotic effect of 1 was suppressed by treatment of cell with rapamycin, a well-known inhibitor of the mTOR signaling pathway, illustrating the selectivity of the compound. Sirolimus 76-85 mechanistic target of rapamycin kinase Homo sapiens 117-121 26311737-9 2015 Furthermore, the inhibition of PI3K/Akt by LY294002/si-Akt or of mTOR by rapamycin augmented LicA-induced apoptosis and autophagy. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 65-69 26358751-3 2015 Current clinical mTOR inhibitors only inhibit the mTORC1 complex and are derivatives of the macrolide rapamycin (rapalogs). Sirolimus 102-111 mechanistic target of rapamycin kinase Homo sapiens 17-21 26208432-8 2015 Using the mTOR inhibitors rapamycin, everolimus and PF-04691502 (a dual PI3K/mTOR inhibitor) and in combination with tamoxifen, significant reduction in mammosphere formation was observed. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 10-14 26208432-8 2015 Using the mTOR inhibitors rapamycin, everolimus and PF-04691502 (a dual PI3K/mTOR inhibitor) and in combination with tamoxifen, significant reduction in mammosphere formation was observed. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 77-81 26123689-7 2015 Sirolimus, which is directed against the PI3/AKT/mTOR downstream signalling pathway involved in lymphangiogenesis, has also shown promising results, although further study is needed. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 49-53 26050578-1 2015 The mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus have shown their efficacy in kidney transplantation, but their wider introduction has been limited by relative high discontinuation rates. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 4-33 26050578-1 2015 The mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus have shown their efficacy in kidney transplantation, but their wider introduction has been limited by relative high discontinuation rates. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 35-39 26644772-5 2015 Sirolimus causes immunosuppressive effects by inhibiting mammalian target of rapamycin (mTOR), and has well known side effects. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 88-92 26722609-0 2015 The mTOR inhibitor sirolimus suppresses renal, hepatic, and cardiac tissue cellular respiration [Retraction]. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 26623104-9 2015 In contrast, treatment with RAPA only significantly inhibited the protein expression of p-mTOR (P<0.05). Sirolimus 28-32 mechanistic target of rapamycin kinase Homo sapiens 90-94 26251974-4 2015 Furthermore, the inhibition of Akt or mTOR with an antagonist (wortmannin or rapamycin) suppressed the stretch-induced increase in glucose consumption, lactate levels, intracellular ATP levels and the expression of mitochondrial ATP synthase and LDHA, indicating the significance of the Akt/mTOR/p70s6k pathway in regulating osteoblastic energy metabolism in response to mechanical stretch. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 38-42 26251974-4 2015 Furthermore, the inhibition of Akt or mTOR with an antagonist (wortmannin or rapamycin) suppressed the stretch-induced increase in glucose consumption, lactate levels, intracellular ATP levels and the expression of mitochondrial ATP synthase and LDHA, indicating the significance of the Akt/mTOR/p70s6k pathway in regulating osteoblastic energy metabolism in response to mechanical stretch. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 291-295 26002629-6 2015 Expression of a rapamycin-resistant and kinase-active mTOR (S2035T, mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR (S2035T/D2357E, mTOR-TE), conferred resistance to rapamycin inhibition of Cd-induced cell death, implying that the preventive effect of rapamycin on Cd-induced neurotoxicity is mTOR kinase activity-dependent. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 54-58 26061549-6 2015 Interestingly, the expression of Klotho, an antiaging gene that suppresses VC, was reduced in calcified vasculature, whereas rapamycin reversed membrane and secreted Klotho decline through mTOR inhibition. Sirolimus 125-134 mechanistic target of rapamycin kinase Homo sapiens 189-193 26002629-6 2015 Expression of a rapamycin-resistant and kinase-active mTOR (S2035T, mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR (S2035T/D2357E, mTOR-TE), conferred resistance to rapamycin inhibition of Cd-induced cell death, implying that the preventive effect of rapamycin on Cd-induced neurotoxicity is mTOR kinase activity-dependent. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 68-72 26002629-6 2015 Expression of a rapamycin-resistant and kinase-active mTOR (S2035T, mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR (S2035T/D2357E, mTOR-TE), conferred resistance to rapamycin inhibition of Cd-induced cell death, implying that the preventive effect of rapamycin on Cd-induced neurotoxicity is mTOR kinase activity-dependent. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 68-72 26002629-6 2015 Expression of a rapamycin-resistant and kinase-active mTOR (S2035T, mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR (S2035T/D2357E, mTOR-TE), conferred resistance to rapamycin inhibition of Cd-induced cell death, implying that the preventive effect of rapamycin on Cd-induced neurotoxicity is mTOR kinase activity-dependent. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 68-72 26002629-6 2015 Expression of a rapamycin-resistant and kinase-active mTOR (S2035T, mTOR-T), but not a rapamycin-resistant and kinase-dead mTOR (S2035T/D2357E, mTOR-TE), conferred resistance to rapamycin inhibition of Cd-induced cell death, implying that the preventive effect of rapamycin on Cd-induced neurotoxicity is mTOR kinase activity-dependent. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 68-72 26041743-3 2015 We tested in this study, the efficacy and safety of the mTOR-inhibitor sirolimus (SRL) plus prednisone (PDN) in patients with ECD. Sirolimus 71-80 mechanistic target of rapamycin kinase Homo sapiens 56-60 26046470-8 2015 Reduced intracellular sirolimus concentration was followed by increased p70S6k phosphorylation suggesting preservation of the mTOR-signaling pathway. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 126-130 26416965-5 2015 Blocking mTOR signaling with rapamycin or PP242 or mitochondrial ATP production (e.g., with CCCP) reduced mitochondrial Ca(2+) uptake and membrane potential, and impaired cellular ATP release and neutrophil chemotaxis. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 9-13 26353013-12 2015 Co-treatment of EBR with rapamycin, an upstream mTOR pathway inhibitor, prevented EBR-induced cell viability loss and PARP cleavage in LNCaP prostate cancer cells, suggesting that EBR could induce ER stress in these cells. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 48-52 25943403-5 2015 Due to lack of treatment options and the involvement of the mTOR pathway in TSC, a trial of an mTOR inhibitor, rapamycin, was initiated. Sirolimus 111-120 mechanistic target of rapamycin kinase Homo sapiens 95-99 26186486-1 2015 BACKGROUND: Sirolimus (SRL), a mammalian target of rapamycin inhibitor, has been used as a de novo base therapy with steroids and mycophenolate mofetil to avoid the use of calcineurin inhibitors. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 31-60 26208739-13 2015 All the observation was confirmed by silencing TS and inactivating the mTOR/p70S6K1 signaling pathway by rapamycin, both of which increased the chemo-sensitizing efficacy of 5-FU. Sirolimus 105-114 mechanistic target of rapamycin kinase Homo sapiens 71-75 26349966-8 2015 Activation of PI3K by 740Y-P treatment leaded to upregulation of p-Akt, mTOR and MMP-9; inactivation of mTOR by Rapamycin treatment inhibited expression MMP-9 while activation of mTOR by l-Leucine treatment enhanced MMP-9 expression in Schisandrin B incubated cells. Sirolimus 112-121 mechanistic target of rapamycin kinase Homo sapiens 104-108 26238486-5 2015 Importantly, however, FOXP3(+) iNKT cells only acquired suppressive abilities when cultured in the presence of the mTOR inhibitor rapamycin. Sirolimus 130-139 mechanistic target of rapamycin kinase Homo sapiens 115-119 26239133-2 2015 Inhibition of mTOR by rapamycin has been shown to attenuate pathological cardiac hypertrophy and improve the function of aging heart, accompanied by an inhibition of the cardiac proteasome activity. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 29388579-6 2015 Improved understanding of the genetic basis of TSC and of the central issue of mTOR overactivation has led to use of pharmacotherapies such as the mTOR inhibitors everolimus and sirolimus in the treatment of TSC disease. Sirolimus 178-187 mechanistic target of rapamycin kinase Homo sapiens 79-83 29388579-6 2015 Improved understanding of the genetic basis of TSC and of the central issue of mTOR overactivation has led to use of pharmacotherapies such as the mTOR inhibitors everolimus and sirolimus in the treatment of TSC disease. Sirolimus 178-187 mechanistic target of rapamycin kinase Homo sapiens 147-151 26302180-3 2015 This function might be crucial for the growth and survival of cancer cells, especially for those resistant to the allosteric mTOR inhibitor rapamycin. Sirolimus 140-149 mechanistic target of rapamycin kinase Homo sapiens 125-129 26202311-0 2015 Downregulation of cancer stem cell properties via mTOR signaling pathway inhibition by rapamycin in nasopharyngeal carcinoma. Sirolimus 87-96 mechanistic target of rapamycin kinase Homo sapiens 50-54 26202311-6 2015 Interestingly, we found that rapamycin inhibited mTOR signaling in addition to simultaneously downregulating the expression of CD44, SOX2 and MMP-2 and that it affected cell growth and tumor size and weight both in vitro and in vivo. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 49-53 26280535-3 2015 In a drug screen to find new SASP regulators, we uncovered the mTOR inhibitor rapamycin as a potent SASP suppressor. Sirolimus 78-87 mechanistic target of rapamycin kinase Homo sapiens 63-67 26048361-2 2015 Inhibition of mTOR by rapamycin can mitigate some of the phenotypic abnormalities associated with TSC and autism, but whether this is due to the mTOR-related function in energy metabolism remains to be elucidated. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 26073719-2 2015 Classic mTOR inhibitors such as rapamycin or everolimus are commonly used in transplant as well as cancer patients to prevent transplant rejection or cancer progression, respectively. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 8-12 26020804-4 2015 Treatment of FaDu and SCC-1 cell lines with rapamycin, an inhibitor of mTOR pathway, also reduced cell viability of HNSCC cells. Sirolimus 44-53 mechanistic target of rapamycin kinase Homo sapiens 71-75 26046303-2 2015 Recently we have shown that rapamycin prevents Cd-induced neuronal cell death by inhibiting mTOR signaling pathway. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 92-96 26287365-9 2015 Additionally, the mTOR inhibitor rapamycin further reduced the cell viability of TSA- and SAHA-treated SGC-996 cells and the phosphorylation of mTOR, whereas the mTOR activator 1,2-dioctanoyl-sn-glycero-3-phosphate (C8-PA) exerted the opposite influence. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 18-22 26287365-9 2015 Additionally, the mTOR inhibitor rapamycin further reduced the cell viability of TSA- and SAHA-treated SGC-996 cells and the phosphorylation of mTOR, whereas the mTOR activator 1,2-dioctanoyl-sn-glycero-3-phosphate (C8-PA) exerted the opposite influence. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 144-148 26287365-9 2015 Additionally, the mTOR inhibitor rapamycin further reduced the cell viability of TSA- and SAHA-treated SGC-996 cells and the phosphorylation of mTOR, whereas the mTOR activator 1,2-dioctanoyl-sn-glycero-3-phosphate (C8-PA) exerted the opposite influence. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 144-148 26349966-8 2015 Activation of PI3K by 740Y-P treatment leaded to upregulation of p-Akt, mTOR and MMP-9; inactivation of mTOR by Rapamycin treatment inhibited expression MMP-9 while activation of mTOR by l-Leucine treatment enhanced MMP-9 expression in Schisandrin B incubated cells. Sirolimus 112-121 mechanistic target of rapamycin kinase Homo sapiens 104-108 26045471-8 2015 Inhibition of mTOR activity by rapamycin or blocking S6 expression by siRNA inhibited GDH and GLS activity, leading to a decrease in glutamine-induced cell proliferation. Sirolimus 31-40 mechanistic target of rapamycin kinase Homo sapiens 14-18 26253949-1 2015 PURPOSE: This phase I/II study sought to determine the safety and maximum tolerated dose (MTD) of the combination of rapamycin, an mTOR inhibitor, with short-course radiotherapy in rectal cancer patients. Sirolimus 117-126 mechanistic target of rapamycin kinase Homo sapiens 131-135 26367731-6 2015 Western-blot and real time-PCR were used to test whether mTOR-signaling pathway was inhibited with rapamycin treatment. Sirolimus 99-108 mechanistic target of rapamycin kinase Homo sapiens 57-61 26367731-9 2015 p-mTOR, p-p70S6K and p-4E-BP1 were expressed in the cytoplasm of SW1990 cells and those proteins were significantly reduced with rapamycin (p < 0.05). Sirolimus 129-138 mechanistic target of rapamycin kinase Homo sapiens 2-6 26006020-9 2015 Fibrin-cultured cells treated with rapamycin, the mTOR pathway inhibitor, had significantly decreased phospho-p70(s6k) and PDX-1 expression. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 50-54 26033306-10 2015 However, a combination of rapamycin (an mTOR inhibitor) and pimasertib did not induce a synergistic effect in endometrial cancer cells, except for HEC-1B cells. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 40-44 27088062-1 2015 BACKGROUND: We hypothesize that the combination of an mTOR inhibitor, sirolimus, with a well-known cytotoxic agent, cyclophosphamide, provides a well-tolerated and promising alternative treatment for advanced, differentiated thyroid cancers (DTC). Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 54-58 26148957-3 2015 Sirolimus inhibits the mammalian target of rapamycin, which acts as a master switch of numerous cellular processes. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 23-52 26257526-4 2015 The tumor had shown significant avidity on PET/CT as well as an evident response to sirolimus (rapamycin, Rapamune ) that supports the utility of mTOR inhibitors as an effective treatment for malignant PEComa. Sirolimus 84-93 mechanistic target of rapamycin kinase Homo sapiens 146-150 25978917-1 2015 BACKGROUND AND OBJECTIVE: Sirolimus (SR) is a lipophilic macrocytic lactone with immunosuppressive properties (mTOR inhibitor) commonly used in solid organ transplantation and recently introduced in the prophylaxis and treatment of graft-versus-host disease. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 111-115 26170311-3 2015 Rapamycin is an allosteric inhibitor of mTOR that selectively inhibits mTORC1. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 40-44 26379864-0 2015 Rapamycin, an mTOR inhibitor, induced apoptosis via independent mitochondrial and death receptor pathway in retinoblastoma Y79 cell. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 26255626-7 2015 Mutations in the FAT domain of MTOR and in RHEB remained sensitive to rapamycin, though several of these mutations demonstrated residual mTOR kinase activity after treatment with rapamycin at clinically relevant doses. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 31-35 26255626-7 2015 Mutations in the FAT domain of MTOR and in RHEB remained sensitive to rapamycin, though several of these mutations demonstrated residual mTOR kinase activity after treatment with rapamycin at clinically relevant doses. Sirolimus 179-188 mechanistic target of rapamycin kinase Homo sapiens 31-35 26255626-7 2015 Mutations in the FAT domain of MTOR and in RHEB remained sensitive to rapamycin, though several of these mutations demonstrated residual mTOR kinase activity after treatment with rapamycin at clinically relevant doses. Sirolimus 179-188 mechanistic target of rapamycin kinase Homo sapiens 137-141 25968579-8 2015 Incubation with rapamycin and AZD8055 indicated that mammalian target of rapamycin complex (mTORC)2, but not mTORC1, also is required for LIF-stimulated glucose uptake. Sirolimus 16-25 mechanistic target of rapamycin kinase Homo sapiens 53-82 25978917-1 2015 BACKGROUND AND OBJECTIVE: Sirolimus (SR) is a lipophilic macrocytic lactone with immunosuppressive properties (mTOR inhibitor) commonly used in solid organ transplantation and recently introduced in the prophylaxis and treatment of graft-versus-host disease. Sirolimus 37-39 mechanistic target of rapamycin kinase Homo sapiens 111-115 26151793-3 2015 Immunosuppressants that inhibit mTOR, such as sirolimus, may be used in combination with a systemic retinoid for chemoprophylaxis of cutaneous malignancies. Sirolimus 46-55 mechanistic target of rapamycin kinase Homo sapiens 32-36 25912929-1 2015 INTRODUCTION: The inhibitors of the mammalian target of rapamycin (mTOR) sirolimus and everolimus are used not only as immunosuppressants after organ transplantation in combination with calcineurin inhibitors (CNIs) but also as proliferation signal inhibitors coated on drug-eluting stents and in cancer therapy. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 36-65 25912929-1 2015 INTRODUCTION: The inhibitors of the mammalian target of rapamycin (mTOR) sirolimus and everolimus are used not only as immunosuppressants after organ transplantation in combination with calcineurin inhibitors (CNIs) but also as proliferation signal inhibitors coated on drug-eluting stents and in cancer therapy. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 67-71 25836987-9 2015 Administration of single high doses of rapamycin to mice, to model the spikes in rapamycin levels that occur in patients with severe diarrheal episodes, resulted in reduced phosphorylation of S6 and AKT in ileal tissues, indicating inhibition of the mTOR complex (mTORC1 and mTORC2). Sirolimus 39-48 mechanistic target of rapamycin kinase Homo sapiens 250-254 25836987-14 2015 Loss of mTOR regulation of NHE3 could mediate the development of diarrhea in patients undergoing rapamycin therapy. Sirolimus 97-106 mechanistic target of rapamycin kinase Homo sapiens 8-12 25813876-6 2015 The mTOR complex (C)1/S6K1 blocker rapamycin inhibited the phosphorylation of IRS-1 at Ser636 in cells overexpressing alpha-Syn, suggesting that mTORC1/S6K1 activation by alpha-Syn causes feedback inhibition of insulin signaling via suppression of IRS-1 function. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 4-8 26094583-1 2015 The mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus has been increasingly used as immunosuppressants for recipients of solid organ transplants. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 4-33 26094583-1 2015 The mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus has been increasingly used as immunosuppressants for recipients of solid organ transplants. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 35-39 26071984-3 2015 A number of studies have indicated that the mTOR inhibitors everolimus and sirolimus suppress cell proliferation and tumor growth in animal models of HCC. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 44-48 26540919-7 2015 The expression levels of P-mTOR, P-70S6, P-4EBP1 in spherical cells were gradually decreased with increasing of the concentrations of rapamycin, but the difference of the expression levels of mTOR, P70S6, 4EBP1 were not significant. Sirolimus 134-143 mechanistic target of rapamycin kinase Homo sapiens 27-31 26540919-8 2015 CONCLUSION: The proteins of mTOR signaling pathway of CSCs in nasopharyngeal carcinoma are overexpressed, and rapamycin can effectively inhibit cell proliferation of CSCs in nasopharyngeal carcinoma by blocking mTOR signaling pathway. Sirolimus 110-119 mechanistic target of rapamycin kinase Homo sapiens 28-32 26540919-8 2015 CONCLUSION: The proteins of mTOR signaling pathway of CSCs in nasopharyngeal carcinoma are overexpressed, and rapamycin can effectively inhibit cell proliferation of CSCs in nasopharyngeal carcinoma by blocking mTOR signaling pathway. Sirolimus 110-119 mechanistic target of rapamycin kinase Homo sapiens 211-215 26087255-1 2015 The direct effect of immunosuppressive drugs calcineurin inhibitor (Tacrolimus, TAC) and mTOR inhibitor (Sirolimus, SRL) on B cell activation, differentiation and proliferation is not well documented. Sirolimus 105-114 mechanistic target of rapamycin kinase Homo sapiens 89-93 26104664-10 2015 CONCLUSIONS: The present data suggests that 20-h exposure of ITA rings to rapamycin reduces endothelium-mediated relaxation through down-regulation of Akt-phosphorylation via the mTOR signalling axis within the ITA tissue without injuring the endothelial cell layer. Sirolimus 74-83 mechanistic target of rapamycin kinase Homo sapiens 179-183 26061184-0 2015 Rapamycin Enhances the Anti-Cancer Effect of Dasatinib by Suppressing Src/PI3K/mTOR Pathway in NSCLC Cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 79-83 26061184-5 2015 Mechanistic investigations demonstrated that FoxO1/FoxO3a and p70S6K/4E-BP1, the molecules at downstream of Src-PI3K-Akt and mTOR signaling, were significantly suppressed by the combined use of Dasatinib and Rapamycin. Sirolimus 208-217 mechanistic target of rapamycin kinase Homo sapiens 125-129 26026094-7 2015 In order to evaluate the effect of rapamycin, a natural inhibitor of mTOR kinase, on S-LAM1 cells, a sulforhodamine B cell viability assay was performed with different concentrations of rapamycin. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 69-73 26053020-9 2015 TUSC2 inhibits mTOR activation and the latter cell lines were responsive to the mTOR inhibitor rapamycin combined with erlotinib. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 80-84 25907074-3 2015 Although rapamycin was originally developed as an inhibitor of T cell proliferation for preventing organ transplant rejection, its molecular target, mTOR, has been subsequently identified as a central regulator of metabolic cues that drive lineage specification in the immune system. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 149-153 25649370-0 2015 Phase 1b study of the mammalian target of rapamycin inhibitor sirolimus in combination with nanoparticle albumin-bound paclitaxel in patients with advanced solid tumors. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 22-51 25851741-6 2015 CONCLUSIONS: Sirolimus-based immunosuppression had a lower incidence of CMV infection compared with conventional prophylaxis therapy and did not increase rejection risks and mortality after liver transplantation, indicating that with the use of an mammalian target-of-rapamycin (mTOR)-inhibitor, CMV prophylaxis may be dispensable. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 248-277 25794661-5 2015 Rapamycin, an inhibitor of mTORC1 (mTOR complex 1) did not elicit apoptosis in lymphoma cells; however, the combination of rapamycin with exogenous TGF-beta1 induced apoptosis and restored TGF-beta1 dependent apoptotic machinery in several lymphoma cell lines with reduced TGF-beta sensitivity in vitro. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 25818165-11 2015 PI3K/Akt/mTOR inhibitor, PF-04691502 and mTOR inhibitor rapamycin enhanced the apoptosis-inducing effect of celastrol. Sirolimus 56-65 mechanistic target of rapamycin kinase Homo sapiens 41-45 26902021-0 2015 Rapamycin-Mediated mTOR Inhibition Reverses Drug Resistance to Adriamycin in Colon Cancer Cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 19-23 25162215-1 2015 BACKGROUND: Sirolimus is an inhibitor of mammalian target of rapamycin, which exhibits large interindividual pharmacokinetic variability. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 41-70 25988388-5 2015 The suppression of HIF-1alpha and VEGF by rapamycin was associated with dephosphorylation of mTOR and the downstream effector ribosomal protein S6 kinase (P70S6K) and 4E-binding protein-1 (4E-BP1) of mTORC1. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 93-97 25151963-9 2015 Conversely, suppression of mTOR with the chemical inhibitors PP242 or rapamycin-sensitized DOV13, an ovarian cancer cell line incapable of inducing REDD1, to orlistat-induced cell death through caspase-2. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 27-31 26191215-0 2015 Rapamycin, a mTOR inhibitor, induced growth inhibition in retinoblastoma Y79 cell via down-regulation of Bmi-1. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 13-17 25833958-5 2015 Whereas in conventional DCs, rapamycin effectively blocks mammalian target of rapamycin (mTOR) 1 signaling induced by Flt3L, increased mTOR1 activity renders pDCs more resistant to inhibition by rapamycin. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 58-87 25833958-5 2015 Whereas in conventional DCs, rapamycin effectively blocks mammalian target of rapamycin (mTOR) 1 signaling induced by Flt3L, increased mTOR1 activity renders pDCs more resistant to inhibition by rapamycin. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 89-93 25833958-5 2015 Whereas in conventional DCs, rapamycin effectively blocks mammalian target of rapamycin (mTOR) 1 signaling induced by Flt3L, increased mTOR1 activity renders pDCs more resistant to inhibition by rapamycin. Sirolimus 78-87 mechanistic target of rapamycin kinase Homo sapiens 89-93 25657110-7 2015 Furthermore, rapamycin, a specific inhibitor of mTOR, almost completely blocked FN-induced phosphorylation of 4E-BP1 and also partially abrogated the stimulatory effects of FN on GBC cell proliferation and invasion. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 48-52 25576058-2 2015 We used a Panc02 pancreatic tumor cell transplant model in diet-induced obese (DIO) C57BL/6 mice to compare the effects of metformin and the direct mammalian target of rapamycin (mTOR) inhibitor rapamycin on PC growth, glucose regulation, mTOR pathway signaling, and candidate microRNA (miR) expression. Sirolimus 168-177 mechanistic target of rapamycin kinase Homo sapiens 179-183 26191215-5 2015 Western blot assay demonstrated that the mTOR pathway in Y79 cells was blocked by rapamycin. Sirolimus 82-91 mechanistic target of rapamycin kinase Homo sapiens 41-45 26191215-8 2015 Together, all these results illustrated that rapamycin induced growth inhibition of human retinoblastoma cells, and inactive of mTOR pathway and downregulation of Bmi-1 was involved in its action mechanism. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 128-132 26176526-2 2015 Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have recently become a treatment option for LAM patients, especially those with extrapulmonary manifestations. Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 0-29 26176526-2 2015 Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have recently become a treatment option for LAM patients, especially those with extrapulmonary manifestations. Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 31-35 25773262-5 2015 Treatment with rapamycin, an mTOR inhibitor, attenuated the proliferation of THP-1 cells. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 29-33 25518065-8 2015 Sirolimus, a mTOR inhibitor, was commenced at 9 weeks of age following which he showed a marked improvement in his glycaemic control. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 13-17 26390657-4 2015 With the intervention of mammalian target of rapamycin mTOR inhibitor rapamycin (100 nmol x L(-1)) , the effect of blocking mTOR signaling pathway on autophagic inhibition of emodin was observed. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 124-128 25899445-4 2015 The mammalian target of rapamycin (mTOR) inhibitor sirolimus (SIR) is an immunosuppressant with strong antiproliferative effects, and is potentially able to stop or reduce cyst growth and preserve renal function in ADPKD. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 4-33 25899445-4 2015 The mammalian target of rapamycin (mTOR) inhibitor sirolimus (SIR) is an immunosuppressant with strong antiproliferative effects, and is potentially able to stop or reduce cyst growth and preserve renal function in ADPKD. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 35-39 25897262-8 2015 Sirolimus and everolimus, two mTOR inhibitors, are effective in stabilizing lung function and reducing the size of chylous effusions, lymphangioleiomyo-mas, and angiomyolipomas. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 30-34 25884947-6 2015 Herein, we report results of administration of rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, and chloroquine, a lysosomal inhibitor which reverses autophagy by accumulating in lysosomes, responsible for blocking autophagy in 20-month old VCPR155H/+ mice. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 86-117 25884947-6 2015 Herein, we report results of administration of rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, and chloroquine, a lysosomal inhibitor which reverses autophagy by accumulating in lysosomes, responsible for blocking autophagy in 20-month old VCPR155H/+ mice. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 119-123 25884947-7 2015 Rapamycin-treated mice demonstrated significant improvement in muscle performance, quadriceps histological analysis, and rescue of ubiquitin, and TDP-43 pathology and defective autophagy as indicated by decreased protein expression levels of LC3-I/II, p62/SQSTM1, optineurin and inhibiting the mTORC1 substrates. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 294-300 25424831-13 2015 Treatment with the mTOR inhibitor rapamycin also diminished cellular proliferation, sprouting and AKT phosphorylation, but only in LM-LEC. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 19-23 25906314-7 2015 Further investigation showed that MTOR activation was enhanced in cilia-suppressed cells and the MTOR inhibitor rapamycin could largely reverse autophagy suppression. Sirolimus 112-121 mechanistic target of rapamycin kinase Homo sapiens 34-38 25906314-7 2015 Further investigation showed that MTOR activation was enhanced in cilia-suppressed cells and the MTOR inhibitor rapamycin could largely reverse autophagy suppression. Sirolimus 112-121 mechanistic target of rapamycin kinase Homo sapiens 97-101 25402866-1 2015 Rapamycin-related mTOR inhibitors (rapalogs) possess immunosuppressive and antiproliferative properties. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 18-22 25644152-2 2015 Rapamycin is an inhibitor of the serine/threonine protein kinase mTOR. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 65-69 25644152-9 2015 Rapamycin alone blocked the mTOR signaling pathway, whereas 3-BrPA did not potentiate this effect. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 28-32 25402866-5 2015 This review presents the clinical experience of rapamycin-related mTOR inhibitors in patients with TSC and summarizes their toxicity profiles in renal transplant and TSC populations. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 66-70 25770080-4 2015 Rapamycin, an inhibitor of mTOR signaling, can exert neuroprotective effects in several CNS diseases. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 25770080-10 2015 Taken together, our findings indicated that mTOR blockade by rapamycin attenuates astrocyte migration, proliferation and production of inflammation mediators. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 44-48 25537496-4 2015 While compounds used to study mTOR signaling, such as rapamycin and related analogs, primarily inhibit mTORC1, prolonged exposure can also disrupt mTORC2 function, confounding interpretation of inhibitor studies. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 30-34 26069529-0 2015 The mTOR inhibitor sirolimus suppresses renal, hepatic, and cardiac tissue cellular respiration. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 25578324-11 2015 Human cerebrovascular smooth muscle cells exposed to purified NOTCH3 ectodomain upregulated BGN, DCN, and COL4A1 through mechanisms that are sensitive to rapamycin, a potent mTOR inhibitor. Sirolimus 154-163 mechanistic target of rapamycin kinase Homo sapiens 174-178 25880415-16 2015 Rapamycin lowered NS levels and inhibited pS65 4E-BP1 phosphorylation in cells with activated Akt-mTOR signaling. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 98-102 25807077-6 2015 Inhibition of mTOR by rapamycin blocked radiation-induced mTOR mitochondrial relocation and the shift of glycolysis to mitochondrial respiration, and reduced the clonogenic survival. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 25807077-6 2015 Inhibition of mTOR by rapamycin blocked radiation-induced mTOR mitochondrial relocation and the shift of glycolysis to mitochondrial respiration, and reduced the clonogenic survival. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 58-62 25749036-8 2015 Mechanistically, treatment with rapamycin, a mTOR inhibitor, inhibited EMT, stem-like capacity and metastasis induced by FBXW7 silencing both in vitro and in vivo. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 45-49 26069529-4 2015 Consistently, inhibitors of mTOR (e.g., rapamycin, also known as sirolimus or Rapamune ) have been shown to impair mitochondrial function. Sirolimus 65-74 mechanistic target of rapamycin kinase Homo sapiens 28-32 25884175-8 2015 Different dosages of p-Akt inhibitor LY294002 (12.5 muM, 25 muM, 50 muM) and p-mTOR inhibitor Rapamycin (25 nM, 50 nM, 100 nM) were given to gastric cancer cell line SGC-7901 in vitro. Sirolimus 94-103 mechanistic target of rapamycin kinase Homo sapiens 79-83 25814705-7 2015 Sirolimus belongs to a novel class of anticancer drugs known as mTOR (mammalian target of Rapamycin) inhibitors. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 64-68 25466898-7 2015 Inhibition of mTOR complex 1 (mTORC1) by rapamycin [drug concentration causing 50% inhibition (IC50) = 5 nM] and mTORC1/mTORC2 by Torin2 (IC50 = 6 nM), or by knocking down key mTORC1/2 components, Raptor and Rictor, respectively, decreased directional cell migration toward CXCL12. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 14-18 25482865-0 2015 Mammalian target of rapamycin inhibitor-associated stomatitis in hematopoietic stem cell transplantation patients receiving sirolimus prophylaxis for graft-versus-host disease. Sirolimus 124-133 mechanistic target of rapamycin kinase Homo sapiens 0-29 25482865-1 2015 The mammalian target of rapamycin (mTOR) inhibitor sirolimus is effective in reducing incidence of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 4-33 25482865-1 2015 The mammalian target of rapamycin (mTOR) inhibitor sirolimus is effective in reducing incidence of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 35-39 25586480-5 2015 In vitro and in vivo experiments with the mTOR inhibitor sirolimus plus gemcitabine showed dramatic results in preclinical models of sarcoma. Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 42-46 25814705-7 2015 Sirolimus belongs to a novel class of anticancer drugs known as mTOR (mammalian target of Rapamycin) inhibitors. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 70-99 26011354-3 2015 Rapamycin, as an inhibitor of mTOR, has been developed as potentially valuable therapeutic agent. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 30-34 26045804-0 2015 The mTOR inhibitor sirolimus suppresses renal, hepatic, and cardiac tissue cellular respiration. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 26045804-4 2015 Consistently, inhibitors of mTOR (e.g., rapamycin, also known as sirolimus or Rapamune ) have been shown to impair mitochondrial function. Sirolimus 65-74 mechanistic target of rapamycin kinase Homo sapiens 28-32 25663935-8 2015 Furthermore, treatment with rapamycin, a specific inhibitor of the mammalian target of rapamycin/p70S6K cascade, resulted in decreased FOXP1 expression in the MCF7 cells, but not in the MDA-MB-231 cells, which were resistant to rapamycin-induced inhibition. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 67-96 25738366-6 2015 Expression of rapamycin-resistant mutant of mTOR (mTOR-T), but not rapamycin-resistant and kinase dead mutant of mTOR (mTOR-TE), prevented rapamycin from inhibiting mSin1 phosphorylation, suggesting that rapamycin-induced dephosphorylation of mSin1 is mTOR-dependent. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 44-48 25738366-6 2015 Expression of rapamycin-resistant mutant of mTOR (mTOR-T), but not rapamycin-resistant and kinase dead mutant of mTOR (mTOR-TE), prevented rapamycin from inhibiting mSin1 phosphorylation, suggesting that rapamycin-induced dephosphorylation of mSin1 is mTOR-dependent. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 50-54 25738366-6 2015 Expression of rapamycin-resistant mutant of mTOR (mTOR-T), but not rapamycin-resistant and kinase dead mutant of mTOR (mTOR-TE), prevented rapamycin from inhibiting mSin1 phosphorylation, suggesting that rapamycin-induced dephosphorylation of mSin1 is mTOR-dependent. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 50-54 25738366-6 2015 Expression of rapamycin-resistant mutant of mTOR (mTOR-T), but not rapamycin-resistant and kinase dead mutant of mTOR (mTOR-TE), prevented rapamycin from inhibiting mSin1 phosphorylation, suggesting that rapamycin-induced dephosphorylation of mSin1 is mTOR-dependent. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 50-54 25738366-6 2015 Expression of rapamycin-resistant mutant of mTOR (mTOR-T), but not rapamycin-resistant and kinase dead mutant of mTOR (mTOR-TE), prevented rapamycin from inhibiting mSin1 phosphorylation, suggesting that rapamycin-induced dephosphorylation of mSin1 is mTOR-dependent. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 50-54 25738366-9 2015 However, silencing mTOR or mLST8 mimicked the effect of rapamycin, inhibiting mSin1 phosphorylation. Sirolimus 56-65 mechanistic target of rapamycin kinase Homo sapiens 19-23 25738366-10 2015 Our findings suggest that rapamycin inhibits mSin1 phosphorylation, which is independent of mTORC1 and mTORC2, but is possibly dependent on a new mTOR complex, which at least contains mTOR and mLST8. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 103-107 25571970-8 2015 Furthermore, the mTOR inhibitor rapamycin increased iso-GNA-induced cell death by enhancing autophagy. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 17-21 25428129-7 2015 Inhibition of mTOR with rapamycin partially suppressed the phosphorylation of PERK and eIF2a and the induction of CHOP and GRP78 induction during tunicamycin treatment. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 14-18 25456069-1 2015 The involvement of mammalian target of rapamycin (mTOR) in lifespan control in invertebrates, calorie-restricted rodents, and extension of mouse lifespan by rapamycin have prompted speculation that diminished mTOR function may contribute to mammalian longevity in several settings. Sirolimus 39-48 mechanistic target of rapamycin kinase Homo sapiens 50-54 25581066-7 2015 Rapamycin-induced suppression of mTOR activity during the early postnatal period enhanced not only autophagy but also developmental reduction of myelinating Schwann cells cytoplasm in vivo. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 33-37 25687356-2 2015 This phase II trial was designed to evaluate the safety and clinical activity of daily oral sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, in combination with trastuzumab in HER2-positive metastatic breast cancer following disease progression on prior trastuzumab therapy. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 105-134 25687356-2 2015 This phase II trial was designed to evaluate the safety and clinical activity of daily oral sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, in combination with trastuzumab in HER2-positive metastatic breast cancer following disease progression on prior trastuzumab therapy. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 136-140 25503302-3 2015 Sirolimus inhibits mammalian target of rapamycin (mTOR), a member the phosphoinositide 3-Kinase signaling pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 19-48 25503302-3 2015 Sirolimus inhibits mammalian target of rapamycin (mTOR), a member the phosphoinositide 3-Kinase signaling pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 50-54 26521828-1 2015 We previously demonstrated that rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), protects against N-methyl-D-aspartic acid (NMDA)-induced retinal neurotoxicity, but the mechanism underlying this protection is not fully understood. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 63-92 25442674-7 2015 Rapamycin (sirolimus) and its analogs known as rapalogues, such as RAD001 (everolimus) and CCI-779 (temsirolimus), suppress mTOR activity through an allosteric mechanism that acts at a distance from the ATP-catalytic binding site, and are considered incomplete inhibitors. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 124-128 25442674-7 2015 Rapamycin (sirolimus) and its analogs known as rapalogues, such as RAD001 (everolimus) and CCI-779 (temsirolimus), suppress mTOR activity through an allosteric mechanism that acts at a distance from the ATP-catalytic binding site, and are considered incomplete inhibitors. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 124-128 25714412-4 2015 Here, we report on the induction of autophagy initiated by the pathogen receptor HSP90AA1 (heat shock protein 90 kDa alpha [cytosolic], class A member 1) via the AKT-MTOR (mechanistic target of rapamycin)-dependent pathway. Sirolimus 194-203 mechanistic target of rapamycin kinase Homo sapiens 166-170 26521828-1 2015 We previously demonstrated that rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), protects against N-methyl-D-aspartic acid (NMDA)-induced retinal neurotoxicity, but the mechanism underlying this protection is not fully understood. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 94-98 26583091-3 2015 In many cases, autophagy is regulated by the phosphatidylinositol 3-phosphate kinase/AKT/mammalian target of rapamycin/p70 ribosomal protein S6 kinase (PI3K/AKT/mTOR/p70S6K) signaling pathway. Sirolimus 109-118 mechanistic target of rapamycin kinase Homo sapiens 161-165 25918725-0 2015 Inhibition of mTOR by Rapamycin Results in Auditory Hair Cell Damage and Decreased Spiral Ganglion Neuron Outgrowth and Neurite Formation In Vitro. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 25945415-3 2015 Suppression of mTOR predominantly causes G1 cell cycle arrest, which likely contributes to the ineffectiveness of rapamycin-based therapeutic strategies. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 15-19 25791172-6 2015 This sequence of events could be prevented by pretreatment with rapamycin (mTOR inhibition) or metformin (enzyme 5"-AMP-activated protein kinase activation). Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 75-79 24882386-6 2015 Under basal conditions, mammalian target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) had the most potent anti-inflammatory effect, decreasing both IL-8 release ( -80%) and vascular endothelial growth factor (VEGF) release ( -65%) and preserving the release of the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1RA). Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 24-53 24882386-6 2015 Under basal conditions, mammalian target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) had the most potent anti-inflammatory effect, decreasing both IL-8 release ( -80%) and vascular endothelial growth factor (VEGF) release ( -65%) and preserving the release of the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1RA). Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 55-59 25034463-7 2015 We measured the activity of mammalian target of rapamycin (mTOR) in the pilocarpine rat model pretreated with the mTOR-specific inhibitor, rapamycin, and SB-399885 using western blotting. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 59-63 25591762-7 2015 In cultured renal fibroblasts, overexpression of AMPKalpha1D157A upregulated mTOR signaling and matrix synthesis, which were ameliorated by co-treatment with the inhibitor of mTOR, rapamycin. Sirolimus 181-190 mechanistic target of rapamycin kinase Homo sapiens 77-81 26351512-6 2015 Interestingly, auraptene induces an increase in the phosphorylation of Akt, which is reminiscent of the effect of rapamycin, the mTOR inhibitor that triggers a negative feedback loop on Akt/mTOR pathway. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 129-133 26351512-6 2015 Interestingly, auraptene induces an increase in the phosphorylation of Akt, which is reminiscent of the effect of rapamycin, the mTOR inhibitor that triggers a negative feedback loop on Akt/mTOR pathway. Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 190-194 26323019-6 2015 However, AICAR also suppresses production of phosphatidic acid (PA), which interacts with mTOR in a manner that is competitive with rapamycin. Sirolimus 132-141 mechanistic target of rapamycin kinase Homo sapiens 90-94 25714699-5 2015 This is the reason to consider the mTOR inhibitors such as rapamycin analogs as an encouraging therapy for malignant glioma, but current investigations suggest that single inhibition of mTOR may be insufficient. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 35-39 25314592-5 2015 Rapamycin, the prototypical inhibitor of the mTOR signaling pathway, has recently emerged as an effective treatment for KS when administered orally. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 45-49 25976336-1 2015 OBJECTIVE: This study aimed to investigate the efficacy of combination of rapamycin, an mammalian target of rapamycin (mTOR) inhibitor for treating rejection after organ transplantation, and oxaliplatin, a third-generation of platinum drug usually used to treat chemoresistant or progressive ovarian cancer, in cisplatin-resistant ovarian carcinoma cells A2780cis. Sirolimus 74-83 mechanistic target of rapamycin kinase Homo sapiens 88-117 25976336-1 2015 OBJECTIVE: This study aimed to investigate the efficacy of combination of rapamycin, an mammalian target of rapamycin (mTOR) inhibitor for treating rejection after organ transplantation, and oxaliplatin, a third-generation of platinum drug usually used to treat chemoresistant or progressive ovarian cancer, in cisplatin-resistant ovarian carcinoma cells A2780cis. Sirolimus 74-83 mechanistic target of rapamycin kinase Homo sapiens 119-123 25587030-9 2014 Either MEK or mTOR was sufficient to phosphorylate these PMA-induced rapamycin-resistant sites because co-treatment with U0126 and rapamycin was required to abrogate them. Sirolimus 69-78 mechanistic target of rapamycin kinase Homo sapiens 14-18 26770837-2 2015 Previous studies have suggested that rapamycin (an mTOR inhibitor) can attenuate nociceptive behaviors in many pain models, most likely at the spinal cord level. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 51-55 25478892-1 2015 Rapamycin, an inhibitor of mTOR activity, is a potent inducer of erythroid differentiation and fetal hemoglobin production in beta-thalassemic patients. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 25628925-4 2015 In the present study, we describe that AZD2014, a small molecular ATP-competitive inhibitor of mTOR, was a highly potent inhibitor of mTORC1 and mTORC2 in human HCC cells, which led to a more thorough inhibition of mTORC1 than rapamycin, and the inhibition of mTORC2 prevented the feedback activation of AKT signaling. Sirolimus 227-236 mechanistic target of rapamycin kinase Homo sapiens 95-99 25453101-10 2014 On the other hand, rapamycin treatment leads to transient appearance of monomeric mTORC1 before complete disruption of the mTOR-raptor interaction, whereas mTORC2 stoichiometry is unaffected. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 82-86 25552900-8 2015 Additionally, mTOR inhibitors (everolimus/sirolimus) were applied since 2003. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 14-18 25388971-7 2014 Rapamycin, an mTOR inhibitor, blocked osteogenic differentiation induced by IGF-1. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 25514416-8 2014 Incubation of cells with rapamycin, a known inhibitor of mTOR kinase activity, increased the total Edc4 protein expression but at the same time decreased the Edc4 interaction with mTORC1. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 57-61 24879590-6 2014 The cell invasiveness induced by LKB1 loss was nearly suppressed by mammalian target of rapamycin (mTOR) inhibitor (rapamycin and everolimus) and mTOR/AKT dual inhibitor Palomid 529 (P529). Sirolimus 88-97 mechanistic target of rapamycin kinase Homo sapiens 99-103 25060812-7 2014 Furthermore, such crosstalk was also noted in an in vivo context, after mTOR inhibition by rapamycin treatment of perinatal pups. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 72-76 25489805-1 2014 OBJECTIVES: The mammalian target of rapamycin inhibitors sirolimus and everolimus are immunosuppressive drugs for kidney transplant patients, but adverse events may include proteinuria. Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 16-45 25580270-4 2014 The major development in the treatment of LAM is the discovery of two mammalian target of rapamycin (mTOR) inhibitors, sirolimus and everolimus, as effective drugs. Sirolimus 119-128 mechanistic target of rapamycin kinase Homo sapiens 70-99 25580270-4 2014 The major development in the treatment of LAM is the discovery of two mammalian target of rapamycin (mTOR) inhibitors, sirolimus and everolimus, as effective drugs. Sirolimus 119-128 mechanistic target of rapamycin kinase Homo sapiens 101-105 25580270-7 2014 Another consequence of mTOR inhibition by sirolimus is an increase in Rho activity, resulting in reduced programmed cell death. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 23-27 25199529-2 2014 Rapamycin, an inhibitor of the mTOR pathway, has been shown in a landmark clinical trial to halt the decline in lung function, as long as it is used continuously. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 31-35 25310356-7 2014 Moreover, the cells treated with the combination of the two agents exhibited significantly decreased protein levels of phosphorylated (p)-p70S6 kinase 1 (Thr389), the downstream effector of mTOR, compared with the cells treated with rapamycin or berberine alone. Sirolimus 233-242 mechanistic target of rapamycin kinase Homo sapiens 190-194 25531195-0 2014 Lung injury associated with mTOR inhibitors (sirolimus and everolimus). Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 28-32 24375594-0 2014 The immunosuppressant tributyltin oxide blocks the mTOR pathway, like rapamycin, albeit by a different mechanism. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 51-55 25347473-5 2014 Indeed, treatment with the clinically available mTOR inhibitor rapamycin suppressed the growth of cancer cells in which PRL was overexpressed. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 48-52 25310356-8 2014 Furthermore, overexpression of cluster of differentiation (CD) 147, a transmembrance glycoprotein associated with the anticancer effects of berberine, was found to upregulate p-mTOR expression and inhibit cell death in SMMC7721 cells co-treated with rapamycin and berberine. Sirolimus 250-259 mechanistic target of rapamycin kinase Homo sapiens 177-181 25464856-3 2014 Blockade of inhibitory receptor programmed cell death protein 1 (PD-1) in vivo increased mTOR activity in virus-specific CTLs, and its therapeutic effects were abrogated by the mTOR inhibitor rapamycin. Sirolimus 192-201 mechanistic target of rapamycin kinase Homo sapiens 89-93 25375091-2 2014 Herein, we showed rapamycin, a MTOR inhibitor and autophagy inducer, could reduce total and phospho-KIT expression levels and enhance apoptosis in imatinib-resistant GIST cells. Sirolimus 18-27 mechanistic target of rapamycin kinase Homo sapiens 31-35 25193464-3 2014 We have used loss-of-function RNAi screens of the mTOR inhibitor rapamycin to identify sensitizers of mTOR inhibition. Sirolimus 65-74 mechanistic target of rapamycin kinase Homo sapiens 50-54 25193464-3 2014 We have used loss-of-function RNAi screens of the mTOR inhibitor rapamycin to identify sensitizers of mTOR inhibition. Sirolimus 65-74 mechanistic target of rapamycin kinase Homo sapiens 102-106 25289568-7 2014 The FRB also binds the mTOR inhibitor rapamycin that has been referred to as an allosteric inhibitor, implying that this inhibitor is actually a competitive inhibitor of the protein substrate. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 23-27 25416705-10 2014 Both the high- and low-risk alleles respond to allosteric mTOR inhibition by rapamycin until, at high drug levels, allelic differences are eliminated. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 58-62 25464856-3 2014 Blockade of inhibitory receptor programmed cell death protein 1 (PD-1) in vivo increased mTOR activity in virus-specific CTLs, and its therapeutic effects were abrogated by the mTOR inhibitor rapamycin. Sirolimus 192-201 mechanistic target of rapamycin kinase Homo sapiens 177-181 25520866-11 2014 Inhibition of mTOR by rapamycin could effectively reduced tumor growth. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 25411474-7 2014 However, we found that rapamycin, in addition to inhibiting the mammalian target of rapamycin (mTOR) pathway, facilitated autophagy and prevented p62 accumulation-induced NF-kappaB activation and tumor cell proliferation. Sirolimus 23-32 mechanistic target of rapamycin kinase Homo sapiens 64-93 25411474-7 2014 However, we found that rapamycin, in addition to inhibiting the mammalian target of rapamycin (mTOR) pathway, facilitated autophagy and prevented p62 accumulation-induced NF-kappaB activation and tumor cell proliferation. Sirolimus 23-32 mechanistic target of rapamycin kinase Homo sapiens 95-99 24810750-0 2014 Laryngomalacia and complicated, life-threatening mTOR-positive Kaposiform hemangioendothelioma cured by Supraglottoplasty and sirolimus. Sirolimus 126-135 mechanistic target of rapamycin kinase Homo sapiens 49-53 24890505-4 2014 Using 3-methyladenine (3-MA) and rapamycin to regulate the activity of mTOR, it was found that the efficiency of neuronal differentiation was affected. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 71-75 24827931-1 2014 Ridaforolimus, a unique non-prodrug analog of rapamycin, is a potent inhibitor of mTOR under development for cancer treatment. Sirolimus 46-55 mechanistic target of rapamycin kinase Homo sapiens 82-86 25270513-8 2014 CONCLUSION: Topical application of 1% RPM can significantly and systematically suppress the PDL-induced early stage of angiogenesis via inhibition of the AKT/mTOR/P70S6K pathway in a rodent model. Sirolimus 38-41 mechanistic target of rapamycin kinase Homo sapiens 158-162 24810750-4 2014 Successfully treatment of the prior fatal course of the KHE with KMP was initiated not till adding the mTOR inhibitor sirolimus to therapy. Sirolimus 118-127 mechanistic target of rapamycin kinase Homo sapiens 103-107 25164809-10 2014 The abundance of PDK4 dictated the responsiveness of cells to the mTOR inhibitor, rapamycin. Sirolimus 82-91 mechanistic target of rapamycin kinase Homo sapiens 66-70 24548545-1 2014 OBJECTIVES: Sirolimus (rapamycin) is a mammalian target of rapamycin (mTOR) inhibitor with antiproliferative activity. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 39-68 24548545-1 2014 OBJECTIVES: Sirolimus (rapamycin) is a mammalian target of rapamycin (mTOR) inhibitor with antiproliferative activity. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 70-74 24548545-1 2014 OBJECTIVES: Sirolimus (rapamycin) is a mammalian target of rapamycin (mTOR) inhibitor with antiproliferative activity. Sirolimus 23-32 mechanistic target of rapamycin kinase Homo sapiens 39-68 24548545-1 2014 OBJECTIVES: Sirolimus (rapamycin) is a mammalian target of rapamycin (mTOR) inhibitor with antiproliferative activity. Sirolimus 23-32 mechanistic target of rapamycin kinase Homo sapiens 70-74 25193511-10 2014 Combination of MEDI-573 with either rapamycin or AZD2014, another mTOR inhibitor (mTORi), significantly enhanced the antitumor activity of MEDI-573, and this response correlated with modulation of AKT and mTOR signaling. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 66-70 25193511-10 2014 Combination of MEDI-573 with either rapamycin or AZD2014, another mTOR inhibitor (mTORi), significantly enhanced the antitumor activity of MEDI-573, and this response correlated with modulation of AKT and mTOR signaling. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 82-86 25175735-5 2014 In vitro, U87 malignant glioblastoma cells formed tube structures similar to HUVECs on Matrigel in 3D culture, and mTOR-specific inhibitor rapamycin inhibited VM formation in the U87 malignant glioblastoma cells under both normoxia and hypoxia. Sirolimus 139-148 mechanistic target of rapamycin kinase Homo sapiens 115-119 25001862-3 2014 In this study, we demonstrate that the PI3K/mTOR pathway is indispensable for eliciting intact type I and III IFN responses in moDCs stimulated with polyI:C. The inhibition of mTOR functionality by rapamycin impairs the pIRF3 and also a few members of the MAPK family, suggesting that mTOR contributes to the activation of multiple signaling pathways in the presence of viral antigens. Sirolimus 198-207 mechanistic target of rapamycin kinase Homo sapiens 44-48 25288394-1 2014 Genetic studies have shown that the tuberous sclerosis complex (TSC) 1-TSC2-mammalian target of Rapamycin (mTOR) and the Hippo-Yes-associated protein 1 (YAP) pathways are master regulators of organ size, which are often involved in tumorigenesis. Sirolimus 96-105 mechanistic target of rapamycin kinase Homo sapiens 107-111 25200144-7 2014 Additionally, the overexpression of duck FST also relieved the inhibition of myoblast proliferation caused by the addition of rapamycin (an mTOR inhibitor) through PI3K/Akt/mTOR signalling. Sirolimus 126-135 mechanistic target of rapamycin kinase Homo sapiens 140-144 25200144-7 2014 Additionally, the overexpression of duck FST also relieved the inhibition of myoblast proliferation caused by the addition of rapamycin (an mTOR inhibitor) through PI3K/Akt/mTOR signalling. Sirolimus 126-135 mechanistic target of rapamycin kinase Homo sapiens 173-177 25043732-9 2014 Together, these results demonstrate that acute blockade of mTOR signaling by acute rapamycin administration not only causes changes in neuronal activity, but also leads to elevated protein expression in protein kinase pathways others than mTOR, contributing to the development of anxiety-like behavior. Sirolimus 83-92 mechanistic target of rapamycin kinase Homo sapiens 59-63 25043732-9 2014 Together, these results demonstrate that acute blockade of mTOR signaling by acute rapamycin administration not only causes changes in neuronal activity, but also leads to elevated protein expression in protein kinase pathways others than mTOR, contributing to the development of anxiety-like behavior. Sirolimus 83-92 mechanistic target of rapamycin kinase Homo sapiens 239-243 25336989-6 2014 Although the clinical trial with temsirolimus, an mTOR inhibitor, did not show any benefit when compared with endocrine therapy alone, a Phase II clinical trial with sirolimus has been promising. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 50-54 25123131-6 2014 The low cytotoxic combination of EPA-FFA 150 microM, EGCG 175 microM and GS extract 15 microM completely inhibited the mTOR signaling in HCT116 and SW480 cells, reaching an effect stronger than or comparable to that of the mTOR inhibitor Rapamycin in HCT116 or SW480 cells, respectively. Sirolimus 238-247 mechanistic target of rapamycin kinase Homo sapiens 119-123 24986086-2 2014 Interestingly, epidemiological studies have shown that patients administered the mammalian target of rapamycin (mTOR) inhibitor, sirolimus (rapamycin), exhibit more favourable outcomes, suggestive of activity against HCMV in vivo. Sirolimus 129-138 mechanistic target of rapamycin kinase Homo sapiens 81-110 24986086-2 2014 Interestingly, epidemiological studies have shown that patients administered the mammalian target of rapamycin (mTOR) inhibitor, sirolimus (rapamycin), exhibit more favourable outcomes, suggestive of activity against HCMV in vivo. Sirolimus 129-138 mechanistic target of rapamycin kinase Homo sapiens 112-116 24986086-2 2014 Interestingly, epidemiological studies have shown that patients administered the mammalian target of rapamycin (mTOR) inhibitor, sirolimus (rapamycin), exhibit more favourable outcomes, suggestive of activity against HCMV in vivo. Sirolimus 101-110 mechanistic target of rapamycin kinase Homo sapiens 112-116 26779398-8 2014 EXPERT OPINION: Targeting mTOR activation with rapamycin analogs sirolimus and everolimus are awaiting approval by the FDA for treatment of LAM. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 26-30 26779398-8 2014 EXPERT OPINION: Targeting mTOR activation with rapamycin analogs sirolimus and everolimus are awaiting approval by the FDA for treatment of LAM. Sirolimus 65-74 mechanistic target of rapamycin kinase Homo sapiens 26-30 25091623-5 2014 However, 3-DSC-mediated HO-1 induction was completely blocked by treatment with cycloheximide, a translational inhibitor, or rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR). Sirolimus 125-134 mechanistic target of rapamycin kinase Homo sapiens 156-185 25091623-5 2014 However, 3-DSC-mediated HO-1 induction was completely blocked by treatment with cycloheximide, a translational inhibitor, or rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR). Sirolimus 125-134 mechanistic target of rapamycin kinase Homo sapiens 187-191 24859454-0 2014 Rapamycin and everolimus facilitate hepatitis E virus replication: revealing a basal defense mechanism of PI3K-PKB-mTOR pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 115-119 25001862-3 2014 In this study, we demonstrate that the PI3K/mTOR pathway is indispensable for eliciting intact type I and III IFN responses in moDCs stimulated with polyI:C. The inhibition of mTOR functionality by rapamycin impairs the pIRF3 and also a few members of the MAPK family, suggesting that mTOR contributes to the activation of multiple signaling pathways in the presence of viral antigens. Sirolimus 198-207 mechanistic target of rapamycin kinase Homo sapiens 176-180 25001862-3 2014 In this study, we demonstrate that the PI3K/mTOR pathway is indispensable for eliciting intact type I and III IFN responses in moDCs stimulated with polyI:C. The inhibition of mTOR functionality by rapamycin impairs the pIRF3 and also a few members of the MAPK family, suggesting that mTOR contributes to the activation of multiple signaling pathways in the presence of viral antigens. Sirolimus 198-207 mechanistic target of rapamycin kinase Homo sapiens 176-180 24804854-1 2014 Mammalian target of rapamycin inhibitors (mTOR-I), everolimus and sirolimus, are immunosuppressive drugs extensively used in renal transplantation. Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 42-46 25257976-0 2014 Effects of the mTOR inhibitor rapamycin on monocyte-secreted chemokines. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 15-19 25109305-6 2014 In order to investigate whether mammalian target of rapamycin (mTOR) is involved in mediating the protective effect of ulinastatin, cells were treated with the mTOR inhibitor, rapamycin 30 min prior to ulinastatin treatment. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 63-67 25380949-3 2014 mTOR inhibitors (mTOR-I, rapamycin/everolimus) may correct underlying defects in TSC. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 0-4 26993551-2 2014 We successfully managed the patient"s severely restricted arm mobility and consumptive coagulopathy with surgical debulking followed by medical therapy with the mammalian target of rapamycin inhibitor sirolimus. Sirolimus 201-210 mechanistic target of rapamycin kinase Homo sapiens 161-190 25060689-3 2014 The events were secondary to the activation of the mammalian-target of rapamycin (mTOR)-pathway induced by leptin, as testified by its reversion induced by mTOR inhibition with rapamycin. Sirolimus 71-80 mechanistic target of rapamycin kinase Homo sapiens 82-86 25060689-3 2014 The events were secondary to the activation of the mammalian-target of rapamycin (mTOR)-pathway induced by leptin, as testified by its reversion induced by mTOR inhibition with rapamycin. Sirolimus 71-80 mechanistic target of rapamycin kinase Homo sapiens 156-160 24943720-2 2014 The mammalian target of rapamycin inhibitors (mTORi) (sirolimus/everolimus) might represent an alternative immunosuppressive regimen with antineoplastic effect. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 4-33 25257976-1 2014 BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and its derivative, everolimus, are potent immunosuppressive and antiproliferative drugs. Sirolimus 69-78 mechanistic target of rapamycin kinase Homo sapiens 12-41 25257976-1 2014 BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and its derivative, everolimus, are potent immunosuppressive and antiproliferative drugs. Sirolimus 69-78 mechanistic target of rapamycin kinase Homo sapiens 43-47 25128827-7 2014 Moreover, PGE2 increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Sirolimus 150-159 mechanistic target of rapamycin kinase Homo sapiens 140-144 25092287-6 2014 mTOR inhibition by rapamycin also down-regulated TCTP protein expression, whereas knockdown or overexpression of TCTP suppressed or activated mTOR signaling, respectively, and affected cell viability. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 0-4 25115395-8 2014 Inhibition of mTOR activity by rapamycin sensitized Aur-A-overexpressed breast cancer cells to metabolic stress-induced cell death. Sirolimus 31-40 mechanistic target of rapamycin kinase Homo sapiens 14-18 25258166-4 2014 She was first treated with a low dose of the mammalian target of rapamycin (mTOR) inhibitor sirolimus (up to 3 mg/day over a 12-month period) and following significant AML size reduction, percutaneous cryoablation was performed. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 45-74 25258166-4 2014 She was first treated with a low dose of the mammalian target of rapamycin (mTOR) inhibitor sirolimus (up to 3 mg/day over a 12-month period) and following significant AML size reduction, percutaneous cryoablation was performed. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 76-80 24898389-2 2014 Interleukin (IL)-12 is critical for the generation of memory CTLs, and inhibition of mammalian target of rapamycin (mTOR) by rapamycin can effectively enhance the memory CTL response. Sirolimus 105-114 mechanistic target of rapamycin kinase Homo sapiens 116-120 25214801-5 2014 Everolimus, a 40-O-(2-hydroxyethyl) derivative of mTOR inhibitor sirolimus, has a distinct pharmacokinetic profile. Sirolimus 65-74 mechanistic target of rapamycin kinase Homo sapiens 50-54 25711103-4 2014 It exists in two mTOR protein complexes mTORC1 and mTORC2 with various sensitivity to the inhibitory effect of rapamycin. Sirolimus 111-120 mechanistic target of rapamycin kinase Homo sapiens 17-21 25180793-1 2014 Rapamycin derivatives allosterically targeting mTOR are currently FDA approved to treat advanced renal cell carcinoma (RCC), and catalytic inhibitors of mTOR/PI3K are now in clinical trials for treating various solid tumors. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 47-51 25180793-4 2014 Catalytic mTOR inhibition with BEZ235 decreased proliferation and increased apoptosis better than allosteric mTOR inhibition with rapamycin. Sirolimus 130-139 mechanistic target of rapamycin kinase Homo sapiens 109-113 24590896-3 2014 Expression of the reactive oxygen species-controlling kinase Mirk/dyrk1B was increased severalfold by the mammalian target of rapamycin (mTOR) inhibitors RAD001, WYE354 and rapamycin, with less effect by the Akt inhibitors AZD5363 and MK-2206. Sirolimus 126-135 mechanistic target of rapamycin kinase Homo sapiens 137-141 25162929-1 2014 OBJECTIVE: To analyze upper-limb lymphedema characteristics of renal transplant recipients taking sirolimus, an mTOR inhibitor. Sirolimus 98-107 mechanistic target of rapamycin kinase Homo sapiens 112-116 24984264-9 2014 The mTOR inhibitor rapamycin can neutralize the protective effects of LL-37 on mitochondria. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 25187723-14 2014 An effective treatment for LAM is now available, namely using a mechanistic target of rapamycin (mTOR) inhibitor such as sirolimus. Sirolimus 121-130 mechanistic target of rapamycin kinase Homo sapiens 97-101 25003665-0 2014 Phase I study and preclinical efficacy evaluation of the mTOR inhibitor sirolimus plus gemcitabine in patients with advanced solid tumours. Sirolimus 72-81 mechanistic target of rapamycin kinase Homo sapiens 57-61 25003665-9 2014 In vitro and in vivo studies suggested mTOR pathway hyperactivation by gemcitabine that was reversed by sirolimus. Sirolimus 104-113 mechanistic target of rapamycin kinase Homo sapiens 39-43 25324684-14 2014 Compared to untreated MCMV-infected control cells, rapamycin treatment resulted in a significant decrease in the cleaved caspase 3 levels as well as a significant decrease in the ratio of phosphorylated mammalian target of rapamycin (mTOR) to total mTOR and in the ratio of phosphorylated P70S6K to total P70S6K. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 203-232 24682598-6 2014 Membrane-associated LRRK2 co-localized to autophagosome membranes following either TLR4 stimulation or mTOR inhibition with rapamycin. Sirolimus 124-133 mechanistic target of rapamycin kinase Homo sapiens 103-107 25324684-14 2014 Compared to untreated MCMV-infected control cells, rapamycin treatment resulted in a significant decrease in the cleaved caspase 3 levels as well as a significant decrease in the ratio of phosphorylated mammalian target of rapamycin (mTOR) to total mTOR and in the ratio of phosphorylated P70S6K to total P70S6K. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 234-238 25324684-14 2014 Compared to untreated MCMV-infected control cells, rapamycin treatment resulted in a significant decrease in the cleaved caspase 3 levels as well as a significant decrease in the ratio of phosphorylated mammalian target of rapamycin (mTOR) to total mTOR and in the ratio of phosphorylated P70S6K to total P70S6K. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 249-253 24842496-5 2014 This review highlights the important and well-described aspects of the critical phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT/mTOR pathway and discusses the mechanisms of action of rapamycin, its clinical efficacy in lymphoid malignancies, and the mechanisms of resistance. Sirolimus 193-202 mechanistic target of rapamycin kinase Homo sapiens 138-142 25116684-0 2014 Rapamycin-Induced apoptosis in HGF-stimulated lens epithelial cells by AKT/mTOR, ERK and JAK2/STAT3 pathways. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 75-79 25116684-6 2014 Further investigation of the underlying mechanism using siRNA transfection revealed that rapamycin could promote apoptosis of LECs via inhibiting HGF-induced phosphorylation of AKT/mTOR, ERK and JAK2/STAT3 signaling molecules. Sirolimus 89-98 mechanistic target of rapamycin kinase Homo sapiens 181-185 25116684-8 2014 Together, these findings suggested that rapamycin-induced apoptosis in HGF-stimulated LECs is accompanied by inhibition of AKT/mTOR, ERK and JAK2/STAT3 pathways, which supports its use to inhibit PCO in preclinical studies and provides theoretical foundation for future possible practice. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 127-131 24914132-3 2014 We show here that rapamycin, an allosteric inhibitor of the mammalian target of rapamycin complexes, facilitates highly efficient lentiviral transduction of mouse and human HSCs and dramatically enhances marking frequency in long-term engrafting cells in mice. Sirolimus 18-27 mechanistic target of rapamycin kinase Homo sapiens 60-89 24891456-2 2014 The aim of the current study is to describe the expression of the mTOR pathway in normal adrenals (NAs) and pathological adrenals and to explore whether there are correlation between the expression of these proteins and the in vitro response to sirolimus. Sirolimus 245-254 mechanistic target of rapamycin kinase Homo sapiens 66-70 24800850-0 2014 Rapamycin enhances cetuximab cytotoxicity by inhibiting mTOR-mediated drug resistance in mesenchymal hepatoma cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 56-60 24800850-9 2014 In addition, the induction of EMT in HuH7 and HepG2 cells significantly decreased cetuximab cytotoxicity; however, rapamycin treatment significantly restored cetuximab sensitivity and decreased mTOR signaling in these cells. Sirolimus 115-124 mechanistic target of rapamycin kinase Homo sapiens 194-198 24991977-6 2014 SUMMARY: Initial studies focused on the ability of the mTOR inhibitor rapamycin to suppress immune responses by inhibiting T cell proliferation. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 55-59 24962700-3 2014 Although mTOR was originally discovered as a target protein of rapamycin, a natural macrolide immunosuppressant, rapamycin mainly inhibits the kinase activity of mTORC1, whereas mTORC2 is affected to a much lesser extent. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 9-13 24366287-8 2014 Rapamycin, an mTOR inhibitor, was used for analysis of the suppressive effect on the Th17 response in vitro. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 24325131-5 2014 Cetuximab in combination with rapamycin had synergistic effects on inhibiting the phosphrylation of proteins in PI3K/AKT/mTOR and Ras/MAPK signaling pathway. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 121-125 25009644-1 2014 The aim of the present study was to investigate whether radiation induces the mammalian target of rapamycin (Rap) (mTOR) signaling pathway in esophageal carcinoma Eca109 cells, and whether mTOR inhibition by rapamycin increases Eca109 cell radiosensitivity. Sirolimus 98-107 mechanistic target of rapamycin kinase Homo sapiens 115-119 24946052-4 2014 Computational analyses suggested components of several signal transduction mechanisms including the AKT (also PKB, protein kinase B)/mTOR (mechanistic target of rapamycin) pathway are overrepresented in EV from PC9R cells. Sirolimus 161-170 mechanistic target of rapamycin kinase Homo sapiens 133-137 25161878-7 2014 The effect of perturbed mTOR activity in ER stressed cells was studied on autophagy and cell viability by using agents causing mTOR pathway inhibition (such as rapamycin or metyrapone). Sirolimus 160-169 mechanistic target of rapamycin kinase Homo sapiens 24-28 24982337-1 2014 BACKGROUND: The aim of this study was to investigate the antitumor effect of rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) signaling, combined with 5-fluorouracil treatment on CT-26 colorectal adenocarcinoma cells implanted into BALB/c mice. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 104-133 25048611-9 2014 Rapamycin, an mTOR-specific inhibitor, reduced the phosphorylation of mTOR signalling pathway and decreased the CD36 translational efficiency and protein level even under inflammatory stress resulting in the alleviation of inflammatory stress-induced hepatic lipid accumulation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 25048611-9 2014 Rapamycin, an mTOR-specific inhibitor, reduced the phosphorylation of mTOR signalling pathway and decreased the CD36 translational efficiency and protein level even under inflammatory stress resulting in the alleviation of inflammatory stress-induced hepatic lipid accumulation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 70-74 23995790-10 2014 Rapamycin, the mTOR inhibitor, significantly reduced Smurf1 protein levels, and Smurf1 was degraded in mitosis. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 15-19 24982384-13 2014 CONCLUSION: Our study confirms that mTOR inhibition with sirolimus/temsirolimus is well-tolerated with good radiological responses, albeit short-lived, and supports its use in PEComas. Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 36-40 24982337-1 2014 BACKGROUND: The aim of this study was to investigate the antitumor effect of rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) signaling, combined with 5-fluorouracil treatment on CT-26 colorectal adenocarcinoma cells implanted into BALB/c mice. Sirolimus 77-86 mechanistic target of rapamycin kinase Homo sapiens 135-139 24944633-0 2014 Interferon-alpha enhances the susceptibility of renal cell carcinoma to rapamycin by suppressing mTOR activity. Sirolimus 72-81 mechanistic target of rapamycin kinase Homo sapiens 97-101 24713582-1 2014 The mammalian target of rapamycin (mTOR) inhibiting drug rapamycin (Sirolimus) has severe side effects in patients including hyperlipidemia, an established risk factor for atherosclerosis. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 35-39 24713582-1 2014 The mammalian target of rapamycin (mTOR) inhibiting drug rapamycin (Sirolimus) has severe side effects in patients including hyperlipidemia, an established risk factor for atherosclerosis. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 4-33 24713582-1 2014 The mammalian target of rapamycin (mTOR) inhibiting drug rapamycin (Sirolimus) has severe side effects in patients including hyperlipidemia, an established risk factor for atherosclerosis. Sirolimus 68-77 mechanistic target of rapamycin kinase Homo sapiens 35-39 24713582-4 2014 By using the mTOR inhibitor rapamycin, we show that SR-BI is down-regulated in human umbilical vein endothelial cells (HUVECs). Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 13-17 24713582-8 2014 We demonstrate that inhibition of mTOR leads to endothelial cell dysfunction and decreased SR-BI expression, which may contribute to atherogenesis during rapamycin treatment. Sirolimus 154-163 mechanistic target of rapamycin kinase Homo sapiens 34-38 24944633-6 2014 IFN-alpha and RPM alone decreased the phosphorylation of mTOR, p70 S6 kinase, S6 and 4E binding protein 1, and IFN-alpha significantly enhanced the RPM-induced suppression of the mTOR pathway. Sirolimus 14-17 mechanistic target of rapamycin kinase Homo sapiens 57-61 24944633-6 2014 IFN-alpha and RPM alone decreased the phosphorylation of mTOR, p70 S6 kinase, S6 and 4E binding protein 1, and IFN-alpha significantly enhanced the RPM-induced suppression of the mTOR pathway. Sirolimus 14-17 mechanistic target of rapamycin kinase Homo sapiens 179-183 24944633-6 2014 IFN-alpha and RPM alone decreased the phosphorylation of mTOR, p70 S6 kinase, S6 and 4E binding protein 1, and IFN-alpha significantly enhanced the RPM-induced suppression of the mTOR pathway. Sirolimus 148-151 mechanistic target of rapamycin kinase Homo sapiens 57-61 24944633-6 2014 IFN-alpha and RPM alone decreased the phosphorylation of mTOR, p70 S6 kinase, S6 and 4E binding protein 1, and IFN-alpha significantly enhanced the RPM-induced suppression of the mTOR pathway. Sirolimus 148-151 mechanistic target of rapamycin kinase Homo sapiens 179-183 24944633-7 2014 However, in RCC cells with low mTOR activity, the synergy of IFN-alpha and RPM was eliminated. Sirolimus 75-78 mechanistic target of rapamycin kinase Homo sapiens 31-35 24012802-4 2014 Systemic blockade of mTOR with rapamycin immediately or 12h after training or reactivation impairs both consolidation and reconsolidation of an auditory fear memory. Sirolimus 31-40 mechanistic target of rapamycin kinase Homo sapiens 21-25 24569835-0 2014 Colocalized delivery of rapamycin and paclitaxel to tumors enhances synergistic targeting of the PI3K/Akt/mTOR pathway. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 106-110 24569835-1 2014 Ongoing clinical trials target the aberrant PI3K/Akt/mammalian target of rapamycin (mTOR) pathway in breast cancer through administration of rapamycin, an allosteric mTOR inhibitor, in combination with paclitaxel. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 84-88 25098457-1 2014 The mammalian target of rapamycin inhibitors (mTOR-I) sirolimus and everolimus represents a class of immunosuppressive drugs largely used in renal transplantation. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 4-33 25098457-1 2014 The mammalian target of rapamycin inhibitors (mTOR-I) sirolimus and everolimus represents a class of immunosuppressive drugs largely used in renal transplantation. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 46-50 25313747-8 2014 In ECs in culture LY294002, an inhibitor of phosphatidylinositol-3-kinase (PI3K)/Akt pathway and rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) reversed the effect of sarcosine. Sirolimus 97-106 mechanistic target of rapamycin kinase Homo sapiens 124-153 24915467-1 2014 The activation of the p53 pathway by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a molecule that mimics metabolic stress, is attenuated by rapamycin, an inhibitor of mTOR kinase, immunosuppressant, and cancer drug. Sirolimus 150-159 mechanistic target of rapamycin kinase Homo sapiens 177-181 24012802-8 2014 These findings also provide evidence for a cogent treatment model for reducing the emotional strength of established, traumatic memories analogous to those observed in acquired anxiety disorders such as posttraumatic stress disorder (PTSD) and specific phobias, through pharmacologic blockade of mTOR using systemic rapamycin following reactivation. Sirolimus 316-325 mechanistic target of rapamycin kinase Homo sapiens 296-300 24685370-1 2014 Mammalian target of rapamycin (mTOR) inhibitors are used as potent immunosuppressive agents in solid-organ transplant recipients (everolimus and sirolimus) and as antineoplastic therapies for various cancers (eg, advanced renal cell carcinoma; everolimus, temsirolimus, ridaforolimus). Sirolimus 145-154 mechanistic target of rapamycin kinase Homo sapiens 0-29 24810875-4 2014 Thus, the systemic treatment with mammalian target of rapamycin inhibitors such as sirolimus and everolimus has recently been established to treat specific tuberous sclerosis complex-associated lesions. Sirolimus 83-92 mechanistic target of rapamycin kinase Homo sapiens 34-63 24682932-0 2014 Rapamycin combined with celecoxib enhanced antitumor effects of mono treatment on chronic myelogenous leukemia cells through downregulating mTOR pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 140-144 24682932-2 2014 We recently found that rapamycin could induce G0/G1 phase arrest and apoptosis and inhibit proliferation of K562 cells through inhibiting mammalian target of rapamycin (mTOR) pathway. Sirolimus 23-32 mechanistic target of rapamycin kinase Homo sapiens 138-167 24682932-2 2014 We recently found that rapamycin could induce G0/G1 phase arrest and apoptosis and inhibit proliferation of K562 cells through inhibiting mammalian target of rapamycin (mTOR) pathway. Sirolimus 23-32 mechanistic target of rapamycin kinase Homo sapiens 169-173 24682932-8 2014 Western blot and reverse transcription PCR (RT-PCR) analysis showed that the expressions of mTOR, 4E-BP1, and p70S6K were all significantly decreased in K562 cells after rapamycin + celecoxib treatment (P < 0.05). Sirolimus 170-179 mechanistic target of rapamycin kinase Homo sapiens 92-96 23740036-1 2014 The mammalian target of the rapamycin (mTOR) inhibitors sirolimus and everolimus are increasingly being used in pediatric kidney transplantation in different combinations and doses. Sirolimus 56-65 mechanistic target of rapamycin kinase Homo sapiens 39-43 24685370-1 2014 Mammalian target of rapamycin (mTOR) inhibitors are used as potent immunosuppressive agents in solid-organ transplant recipients (everolimus and sirolimus) and as antineoplastic therapies for various cancers (eg, advanced renal cell carcinoma; everolimus, temsirolimus, ridaforolimus). Sirolimus 145-154 mechanistic target of rapamycin kinase Homo sapiens 31-35 24682932-9 2014 In conclusion, rapamycin combined with celecoxib could induce cell cycle arrest and apoptosis and decrease the expressions of mTOR, 4E-BP1, and p70S6K. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 126-130 24964744-5 2014 Combination of EGFR inhibitors with either the PI3K inhibitor ZSTK474 or the MTOR inhibitor sirolimus showed increased activity. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 77-81 24814708-5 2014 Biliverdin administration inhibited lipopolysaccharide (LPS)-induced C5aR expression (without altering basal expression), an effect partially blocked by rapamycin, an inhibitor of mTOR signaling. Sirolimus 153-162 mechanistic target of rapamycin kinase Homo sapiens 180-184 24936148-7 2014 These effects of S100A4 were abolished by treatment with either the specific PI3K/Akt inhibitor LY294002, or the specific mTOR/p70S6K inhibitor rapamycin. Sirolimus 144-153 mechanistic target of rapamycin kinase Homo sapiens 122-126 24910976-5 2014 Topical use of the mTOR inhibitor rapamycin is an effective treatment for the skin tumours (angiofibromas) in tuberous sclerosis complex, which is also characterised by mTOR deregulation. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 19-23 24910976-5 2014 Topical use of the mTOR inhibitor rapamycin is an effective treatment for the skin tumours (angiofibromas) in tuberous sclerosis complex, which is also characterised by mTOR deregulation. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 169-173 24532005-12 2014 The suppressive effect of Lys on the proteolysis by the autophagic-lysosomal system was maintained partially when mTOR activity was inhibited by 100 nM rapamycin, suggesting that some regulator other than mTOR signaling, for example, Akt, might also suppress the autophagic-lysosomal system. Sirolimus 152-161 mechanistic target of rapamycin kinase Homo sapiens 114-118 24623173-7 2014 To elucidate the effect of autophagy on apoptosis, the mechanically-injured neurons were treated with the mTOR inhibitor rapamycin and 3-methyl adenine (3-MA), which are known to regulate autophagy positively and negatively, respectively. Sirolimus 121-130 mechanistic target of rapamycin kinase Homo sapiens 106-110 24813579-3 2014 Switch of the immunosuppressive regimen to mTOR-inhibitors such as everolimus or sirolimus can have an antitumor effect. Sirolimus 81-90 mechanistic target of rapamycin kinase Homo sapiens 43-47 24676456-3 2014 In the present study, we demonstrate that an mTOR inhibitor, rapamycin, induces autophagy in the Nara-H malignant fibrous histiocytoma (MFH) cell line through the activation of ERK1/2. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 45-49 24411482-6 2014 Specifically, we show that rapamycin, an mTOR inhibitor, prevents the detrimental effects of sucrose in the brain without altering changes in peripheral insulin resistance. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 41-45 24688046-9 2014 mTOR-targeting drugs (rapamycin and AZD8055) significantly reduced proliferation of PELP1-overexpressed breast cancer cells in both in vitro and in vivo xenograft tumor models. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 0-4 24737099-9 2014 The decrease in the expression and phosphorylation of mTOR and its downstream kinases may be one of the molecular mechanisms underlying rapamycin resistance. Sirolimus 136-145 mechanistic target of rapamycin kinase Homo sapiens 54-58 24932295-5 2014 Furthermore, the selected inhibitors of PI3K (LY294002), Akt (SH-6) and mTOR (rapamycin) enhanced the effects of resveratrol in K562 cells. Sirolimus 78-87 mechanistic target of rapamycin kinase Homo sapiens 72-76 24851266-5 2014 Sirolimus is a macrolide antibiotic that inhibits mTOR activity. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 50-54 24641525-5 2014 Sirolimus antagonizes the mTOR pathway, which regulates cell proliferation, differentiation, and migration, and is being studied as an anti-neoplastic agent for solid tumors. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 26-30 24851266-7 2014 In stratum 2, we sought to determine whether the mTOR inhibitor sirolimus in subjects with NF1 results in objective radiographic responses in inoperable PNs in the absence of documented radiographic progression at trial entry. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 49-53 24810045-7 2014 Evidence supporting a key role of mTOR/PP2A signaling included the finding that, similar to metformin, the canonical mTOR inhibitor rapamycin was capable of lowering the ratio of phospho-Ser129 alpha-synuclein to total alpha-synuclein. Sirolimus 132-141 mechanistic target of rapamycin kinase Homo sapiens 34-38 24861504-4 2014 Pharmacokinetic studies have shown that mTOR inhibitors, everolimus (EVR) and sirolimus (SRL), have a large intra- and inter-patient variability in drug exposure, and narrow therapeutic windows (trough levels [C0] 3-8 ng/mL and 5-15 ng/mL, respectively). Sirolimus 78-87 mechanistic target of rapamycin kinase Homo sapiens 40-44 24935295-1 2014 BACKGROUND: Based on evidence available in the literature, rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, but not calcineurin inhibitors (CNIs), has been shown to decrease spleen size. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 72-101 24935295-1 2014 BACKGROUND: Based on evidence available in the literature, rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, but not calcineurin inhibitors (CNIs), has been shown to decrease spleen size. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 103-107 24861463-10 2014 Mechanistically, regulation of G6PD via AR in both hormone-sensitive and castration-resistant models of prostate cancer was abolished following rapamycin treatment, indicating that AR increased flux through the pentose phosphate pathway by the mammalian target of rapamycin (mTOR)-mediated upregulation of G6PD. Sirolimus 144-153 mechanistic target of rapamycin kinase Homo sapiens 244-273 24861463-10 2014 Mechanistically, regulation of G6PD via AR in both hormone-sensitive and castration-resistant models of prostate cancer was abolished following rapamycin treatment, indicating that AR increased flux through the pentose phosphate pathway by the mammalian target of rapamycin (mTOR)-mediated upregulation of G6PD. Sirolimus 144-153 mechanistic target of rapamycin kinase Homo sapiens 275-279 24904824-4 2014 The initial mTOR inhibitor, sirolimus (also known as rapamycin), was first discovered in 1975 in the soil of Easter Island. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 12-16 24904824-6 2014 Shortly thereafter, recognition of sirolimus"s ability to inhibit cellular proliferation and cell cycle progression brought sirolimus to the forefront as a possible inhibitor of mTOR. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 178-182 24904824-6 2014 Shortly thereafter, recognition of sirolimus"s ability to inhibit cellular proliferation and cell cycle progression brought sirolimus to the forefront as a possible inhibitor of mTOR. Sirolimus 124-133 mechanistic target of rapamycin kinase Homo sapiens 178-182 24614082-4 2014 Combining the mTOR inhibitor rapamycin with ABT-737 rescued this resistance mechanism, was highly synergistic in vitro, and provided durable tumor regressions in vivo without notable hematologic suppression. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 14-18 24607296-3 2014 Here, we demonstrated that rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), markedly protected 661W photoreceptor cells from visible light exposure-induced damage at the nanomolar level. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 58-87 24607296-3 2014 Here, we demonstrated that rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), markedly protected 661W photoreceptor cells from visible light exposure-induced damage at the nanomolar level. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 89-93 24989291-5 2014 It is concluded that rapamycin plays an critical role in inhibiting cell proliferation, cell cycles, and adipogenesis, these effects may be related with the autophagy activation and mTOR inhibition resulting from rapamycin. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 182-186 24866893-5 2014 The present study implicated the PI3K/AKT/mTOR pathway in the regulation of FASN expression in ER/HER2-positive breast cancer cells and demonstrated that rapamycin, an mTOR inhibitor, inhibited FASN expression. Sirolimus 154-163 mechanistic target of rapamycin kinase Homo sapiens 42-46 24866893-5 2014 The present study implicated the PI3K/AKT/mTOR pathway in the regulation of FASN expression in ER/HER2-positive breast cancer cells and demonstrated that rapamycin, an mTOR inhibitor, inhibited FASN expression. Sirolimus 154-163 mechanistic target of rapamycin kinase Homo sapiens 168-172 24630930-10 2014 Inhibition of PI3K and mTOR by LY295002 and rapamycin, respectively, decreases the phosphorylation of downstream targets (i.e. GSK3beta and p70S6K) and leads to an increase of catalase expression only in MCF-7 but not in Resox cells. Sirolimus 44-53 mechanistic target of rapamycin kinase Homo sapiens 23-27 24810045-7 2014 Evidence supporting a key role of mTOR/PP2A signaling included the finding that, similar to metformin, the canonical mTOR inhibitor rapamycin was capable of lowering the ratio of phospho-Ser129 alpha-synuclein to total alpha-synuclein. Sirolimus 132-141 mechanistic target of rapamycin kinase Homo sapiens 117-121 24217803-9 2014 In particular, data regarding the role of mammalian target of rapamycin inhibitors (mTORi), such as sirolimus and everolimus, in the PRO development are still controversial. Sirolimus 100-109 mechanistic target of rapamycin kinase Homo sapiens 42-71 24518659-9 2014 Downregulation of mTOR by siRNA or rapamycin significantly inhibited osteoblastic differentiation of VSMCs and decreased the expression and phosphorylation of mTOR and P70 ribosomal S6 kinase in a time- and concentration-dependent manner. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 18-22 24518659-9 2014 Downregulation of mTOR by siRNA or rapamycin significantly inhibited osteoblastic differentiation of VSMCs and decreased the expression and phosphorylation of mTOR and P70 ribosomal S6 kinase in a time- and concentration-dependent manner. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 159-163 24043497-5 2014 However, clinical trials with rapamycin, an effective inhibitor of mTOR, have not been up to the created expectations and a plausible explanation is missing. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 67-71 24732420-8 2014 Further signaling dissection revealed that PDGF-BB posttranscriptional upregulated p21WAF1/Cip1 protein expression, which was inhibited by rapamycin, an activator of autophagy via suppressing mammalian target of rapamycin (mTOR), rather than MG132, a proteasome inhibitor. Sirolimus 139-148 mechanistic target of rapamycin kinase Homo sapiens 192-221 24685479-1 2014 Rapamycin, a mammalian target of rapamycin (mTOR)-specific inhibitor, has the effect of anti-lipid deposition on non-alcoholic fatty liver disease (NAFLD), but the mechanisms with which rapamycin alleviates hepatic steatosis are not fully disclosed. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 44-48 24685479-9 2014 We further confirmed that rapamycin inhibited the phosphorylation of mTOR and its downstream translational regulators including p70 ribosomal protein S6 kinase (p70S6K), eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), and eukaryotic initiation factor 4E (eIF4E). Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 69-73 24685479-10 2014 This study demonstrates that rapamycin inhibits hepatic CD36 translational efficiency through the mTOR pathway, resulting in reduction of CD36 protein expression and alleviation of hepatic steatosis. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 98-102 23708663-0 2014 Accumulation of dephosphorylated 4EBP after mTOR inhibition with rapamycin is sufficient to disrupt paracrine transformation by the KSHV vGPCR oncogene. Sirolimus 65-74 mechanistic target of rapamycin kinase Homo sapiens 44-48 24732420-8 2014 Further signaling dissection revealed that PDGF-BB posttranscriptional upregulated p21WAF1/Cip1 protein expression, which was inhibited by rapamycin, an activator of autophagy via suppressing mammalian target of rapamycin (mTOR), rather than MG132, a proteasome inhibitor. Sirolimus 139-148 mechanistic target of rapamycin kinase Homo sapiens 223-227 24667713-1 2014 BACKGROUND: Everolimus, an orally administered rapamycin analogue, inhibits the mammalian target of rapamycin (mTOR), a highly conserved intracellular serine-threonine kinase that is a central node in a network of signaling pathways controlling cellular metabolism, growth, survival, proliferation, angiogenesis, and immune function. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 80-109 24667713-1 2014 BACKGROUND: Everolimus, an orally administered rapamycin analogue, inhibits the mammalian target of rapamycin (mTOR), a highly conserved intracellular serine-threonine kinase that is a central node in a network of signaling pathways controlling cellular metabolism, growth, survival, proliferation, angiogenesis, and immune function. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 111-115 24534455-3 2014 A large body of evidence indicates that mammalian target of rapamycin (mTOR) inhibitors such as rapamycin or everolimus have pleiotropic anti-atherosclerotic effects so that these drugs can be used as add-on therapy to prevent or delay the pathogenesis of atherosclerosis. Sirolimus 60-69 mechanistic target of rapamycin kinase Homo sapiens 71-75 24458007-4 2014 The same as in nucleated mammalian cells, autophagy was stimulated by cell starvation or the MTOR inhibitor rapamycin in a phosphatidylinositol 3-kinase (PtdIns3K)-dependent manner. Sirolimus 108-117 mechanistic target of rapamycin kinase Homo sapiens 93-97 24549759-6 2014 Recently, biologically targeted pharmacotherapy with mammalian target of rapamycin (mTOR) inhibitors such as sirolimus and everolimus has provided a safe and efficacious treatment option for patients with SEGAs. Sirolimus 109-118 mechanistic target of rapamycin kinase Homo sapiens 53-82 24549759-6 2014 Recently, biologically targeted pharmacotherapy with mammalian target of rapamycin (mTOR) inhibitors such as sirolimus and everolimus has provided a safe and efficacious treatment option for patients with SEGAs. Sirolimus 109-118 mechanistic target of rapamycin kinase Homo sapiens 84-88 24366516-4 2014 We describe a therapeutic attempt with the mammalian target of rapamycin (mTOR) inhibitor sirolimus for a PHTS patient suffering from thymus hyperplasia and lipomatosis. Sirolimus 90-99 mechanistic target of rapamycin kinase Homo sapiens 43-72 24319109-9 2014 Although rapamycin treatment induced autophagy and led to apoptosis promotion, the pro-apoptotic effect of rapamycin was reversed by the addition of 3-MA, suggesting that mTOR inhibition promotes endometriotic cell apoptosis via autophagy induction. Sirolimus 107-116 mechanistic target of rapamycin kinase Homo sapiens 171-175 25852858-1 2014 Mammalian target of rapamycin inhibitor (mTOR-I)/proliferation signal inhibitors (PSI) including sirolimus and everolimus represent a new class of drugs increasingly used in solid-organ transplantation as alternatives to calcineurin inhibitors for patients with renal dysfunction, transplant coronary arterial vasculopathy or malignancy. Sirolimus 97-106 mechanistic target of rapamycin kinase Homo sapiens 0-29 24366516-4 2014 We describe a therapeutic attempt with the mammalian target of rapamycin (mTOR) inhibitor sirolimus for a PHTS patient suffering from thymus hyperplasia and lipomatosis. Sirolimus 90-99 mechanistic target of rapamycin kinase Homo sapiens 74-78 24675464-5 2014 However, 3 days following ligation with rapamycin treatment, a selective mTOR inhibitor, gland weights were maintained, 4E-BP1 and S6rp phosphorylation was inhibited, and there were morphological signs of recovery from atrophy. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 73-77 24691473-6 2014 Treatment of those same cells used in the imatinib studies with rapamycin, an inhibitor of mTOR, resulted in elevated GPx-1 and GPx-4 protein levels independent of Bcr-Abl expression. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 91-95 24675464-6 2014 However, following 5 and 7 days of ligation and rapamycin treatment, glands expressed active mTOR and showed signs of considerable atrophy. Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 93-97 24675464-7 2014 This evidence suggests that inhibition of mTOR by rapamycin delays ligation-induced atrophy of salivary glands. Sirolimus 50-59 mechanistic target of rapamycin kinase Homo sapiens 42-46 24451985-9 2014 Furthermore, VEGF significantly stimulated proliferation and migration of pTr cells, but these effects were blocked by SB203580, U0126, rapamycin, and LY294002, which inhibit p38 MAPK, ERK1/2, mTOR, and PI3K, respectively. Sirolimus 136-145 mechanistic target of rapamycin kinase Homo sapiens 193-197 24645945-3 2014 We examined the effectiveness of the mammalian target of rapamycin (mTOR) inhibitor sirolimus in four infants with severe hyperinsulinemic hypoglycemia that had been unresponsive to maximal doses of diazoxide (20 mg per kilogram of body weight per day) and octreotide (35 mug per kilogram per day). Sirolimus 84-93 mechanistic target of rapamycin kinase Homo sapiens 37-66 24645945-3 2014 We examined the effectiveness of the mammalian target of rapamycin (mTOR) inhibitor sirolimus in four infants with severe hyperinsulinemic hypoglycemia that had been unresponsive to maximal doses of diazoxide (20 mg per kilogram of body weight per day) and octreotide (35 mug per kilogram per day). Sirolimus 84-93 mechanistic target of rapamycin kinase Homo sapiens 68-72 24508654-11 2014 Both rapamycin and cardamonin decreased the phosphorylation of mTOR and p70S6K in two kinds of transfected cells. Sirolimus 5-14 mechanistic target of rapamycin kinase Homo sapiens 63-67 24462935-9 2014 Our findings demonstrated that toxicity of simulated ischemia conditions were enhanced in HUVEC when autophagy was blocked, and that rapamycin effectively prevented OGD-evoked damage by induction of protective autophagy via inhibition of the mTOR pathway. Sirolimus 133-142 mechanistic target of rapamycin kinase Homo sapiens 242-246 24334270-7 2014 As the mTOR inhibitor rapamycin up-regulated PDCD4 mRNA levels, the PI3K-Akt-mTOR signaling pathway may control the transcription of the PDCD4 gene as well as the degradation of the protein. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 7-11 24603487-6 2014 PTEN and p-Akt downregulation could be abrogated by both the PI3K inhibitor LY294002 and the mTOR inhibitor rapamycin. Sirolimus 108-117 mechanistic target of rapamycin kinase Homo sapiens 93-97 24508508-3 2014 Rapamycin, a specific inhibitor of mTOR, has been shown to be useful in the treatment of certain diseases. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 35-39 24334270-7 2014 As the mTOR inhibitor rapamycin up-regulated PDCD4 mRNA levels, the PI3K-Akt-mTOR signaling pathway may control the transcription of the PDCD4 gene as well as the degradation of the protein. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 77-81 23564336-10 2014 CONCLUSIONS: The calcineurin inhibitor cyclosporine A and the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, improve the course of AIP in MRL/Mp mice via different mechanisms. Sirolimus 82-91 mechanistic target of rapamycin kinase Homo sapiens 93-97 24464150-4 2014 This paper wants to share experience of mTOR inhibitors sirolimus in the treatment of refractory KHE. Sirolimus 56-65 mechanistic target of rapamycin kinase Homo sapiens 40-44 24658085-7 2014 In vivo, the combination of rapamycin and pemetrexed inhibited growth of NSCLC xenografts, which correlated with decreased mTOR activity and suppression of pemetrexed-induced TS expression. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 123-127 24429254-3 2014 Here we evaluate the synergy of pharmacologically affecting both of these critical pathways using the mTOR inhibitor sirolimus and the histone deacetylase inhibitor entinostat. Sirolimus 117-126 mechanistic target of rapamycin kinase Homo sapiens 102-106 23741975-0 2014 Rapamycin interacts synergistically with idarubicin to induce T-leukemia cell apoptosis in vitro and in a mesenchymal stem cell simulated drug-resistant microenvironment via Akt/mammalian target of rapamycin and extracellular signal-related kinase signaling pathways. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 178-207 23741975-4 2014 Combined treatment with rapamycin and IDA down-regulated Bcl-2 and Mcl-1, and inhibited the activation of phosphoinositide 3-kinase (PI3K)/mTOR and extracellular signal-related kinase (ERK). Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 139-143 24528777-7 2014 Since mycobacterial killing could be observed only at fairly high concentrations of the mTOR inhibitors, exceeding doses necessary to inhibit mTOR, we hypothesized that high doses of Rapamycin, the most commonly utilized mTOR inhibitor for inducing autophagic killing, may exert a direct bactericidal effect on the mycobacteria. Sirolimus 183-192 mechanistic target of rapamycin kinase Homo sapiens 88-92 24575738-4 2014 Since the mTOR pathway is often altered in PEComas and responses have been reported with mTOR-inhibitors such as sirolimus or temsirolimus, we decided to start a neoadjuvant treatment with sirolimus. Sirolimus 129-138 mechanistic target of rapamycin kinase Homo sapiens 10-14 24575738-9 2014 For patients with a large and histologically aggressive PEComa, we think that neoadjuvant treatment with mTOR-inhibitor sirolimus may be considered to facilitate surgery and allow early control of a potentially metastatic disease. Sirolimus 120-129 mechanistic target of rapamycin kinase Homo sapiens 105-109 24558502-6 2014 Rapamycin, a mTOR inhibitor, is effective in treating TSC-associated angiofibromas. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 13-17 24575738-4 2014 Since the mTOR pathway is often altered in PEComas and responses have been reported with mTOR-inhibitors such as sirolimus or temsirolimus, we decided to start a neoadjuvant treatment with sirolimus. Sirolimus 113-122 mechanistic target of rapamycin kinase Homo sapiens 89-93 24586420-2 2014 Analogs of the allosteric mTOR inhibitor rapamycin are approved for mantle cell lymphoma but have limited efficacy in other blood cancers. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 26-30 24586420-3 2014 ATP-competitive "active-site" mTOR inhibitors produce more complete mTOR inhibition and are more effective than rapamycin in preclinical models of leukemia, lymphoma and multiple myeloma. Sirolimus 112-121 mechanistic target of rapamycin kinase Homo sapiens 30-34 24226526-2 2014 Many of these advances originated from studies of the genetic disease tuberous sclerosis complex (TSC), leading to one of the clearest therapeutic opportunities to target mTOR with rapamycin and its analogs ("rapalogs"), which effectively inhibit mTOR complex 1 (mTORC1) by an allosteric mechanism. Sirolimus 181-190 mechanistic target of rapamycin kinase Homo sapiens 171-175 24462769-8 2014 In addition, chronic treatment with rapamycin, a condition known to interfere with assembly of mTORC2, reduces the interaction between Gbetagamma and mTOR and the phosphorylation of AKT; whereas overexpression of Galphai interfered with the effect of Gbetagamma as promoter of p70S6K and AKT phosphorylation. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 95-99 24300666-4 2014 The MTOR inhibitor rapamycin was used as a reference treatment to emphasize the differences between an MTOR-dependent and -independent autophagy-induction. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 24057571-8 2014 Treatment with rapamycin, an mTOR inhibitor, MK2206, an Akt inhibitor, and BI-D1870, a RSK inhibitor, partially suppressed CdCl2-induced ATF4 expression. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 29-33 24067927-9 2014 The STS- and C.C-induced dopaminergic neurite outgrowth was suppressed by rapamycin, an mTOR inhibitor. Sirolimus 74-83 mechanistic target of rapamycin kinase Homo sapiens 88-92 24269559-5 2014 Rapamycin (1muM) inhibited ecdysteroid secretion in Carcinus maenas and Gecarcinus lateralis YOs in vitro, indicating that ecdysteroidogenesis requires mTOR-dependent protein synthesis. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 152-156 24101601-8 2014 These data demonstrate the potential for pharmacological inhibition of mTOR kinase activity to activate mitophagy as a strategy to drive selection against a heteroplasmic mtDNA G11778A mutation and raise the exciting possibility that rapamycin may have therapeutic potential for the treatment of mitochondrial disorders associated with heteroplasmic mtDNA mutations, although further studies are needed to determine if a similar strategy will be effective for other mutations and other cell types. Sirolimus 234-243 mechanistic target of rapamycin kinase Homo sapiens 71-75 23853042-5 2014 The mTOR inhibitors such as rapamycin have been proven to ameliorate the AD-like pathology and cognitive deficits effectively in a broad range of animal models. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 4-8 24377908-1 2014 Sirolimus and its derivate everolimus are two immunosuppressive drugs with similar chemical structure that inhibit the proliferation of T cells by interfering with a serine-threonine kinase, called mTOR. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 198-202 23954967-2 2014 3-Methyladenine (3-MA) is a selective inhibitor of autophagy, whereas rapamycin, an antifungal agent, is a specific inducer of autophagy, inhibiting the protein mammalian target of rapamycin. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 161-190 24505621-7 2014 Additionally, while the autophagy inhibitor chloroquine had no effect, significant neuroprotection was seen instead with two drugs that enhance autophagy induction by different mechanisms, rapamycin (mTOR-dependent) and trehalose (mTOR-independent). Sirolimus 189-198 mechanistic target of rapamycin kinase Homo sapiens 200-204 24438107-10 2014 The anti-proliferation effect and mTOR inhibition ability of rapamycin-loaded PHBHHxPEG NPs was stronger than that of drug-loaded PHBHHx NPs and free rapamycin. Sirolimus 61-70 mechanistic target of rapamycin kinase Homo sapiens 34-38 24395633-3 2014 Against this background, we report a dramatic response in a young patient with advanced HL refractory to the standard treatment who responded to the combination of a pan-histone deacetylase inhibitor (vorinostat, suberoylanilide hydroxamic acid, SAHA) and mammalian target of rapamycin (mTOR) inhibitor therapy (sirolimus,rapamume). Sirolimus 312-321 mechanistic target of rapamycin kinase Homo sapiens 256-285 24395633-3 2014 Against this background, we report a dramatic response in a young patient with advanced HL refractory to the standard treatment who responded to the combination of a pan-histone deacetylase inhibitor (vorinostat, suberoylanilide hydroxamic acid, SAHA) and mammalian target of rapamycin (mTOR) inhibitor therapy (sirolimus,rapamume). Sirolimus 312-321 mechanistic target of rapamycin kinase Homo sapiens 287-291 24395633-12 2014 The morphoproteomic/morphometric findings in this "unusual responder" patient"s relapsed HL that correlate best, as a response signature with the subsequent clinical remission following rapamycin (sirolimus) and vorinostat (SAHA) therapies, center on an immune dysregulation involving an imbalance between effector and functional T regulatory cells in addition to targeting the mTOR pathway. Sirolimus 186-195 mechanistic target of rapamycin kinase Homo sapiens 378-382 24603476-3 2014 The present study was designed to explore the renoprotective potential of low-dose mammalian target of rapamycin (mTOR) inhibitor rapamycin in an IgAN rat model and the possible mechanism of action. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 114-118 24316214-9 2014 Further, mTOR inhibition by rapamycin, or by mTOR siRNA knockdown, diminished alpha-MSH"s pro-survival effect in RPE cells. Sirolimus 28-37 mechanistic target of rapamycin kinase Homo sapiens 9-13 24835866-4 2014 To examine its mechanism of action, we performed genomewide microarray on human fibroblasts (from normal skin, HTS, and keloid scars) treated with the mTOR inhibitor, rapamycin. Sirolimus 167-176 mechanistic target of rapamycin kinase Homo sapiens 151-155 24018642-6 2014 Combination of rapamycin with sunitinib resulted in enhanced cell cycle arrest in G1 phase, which was accompanied with enhanced suppression of mTOR signaling and disruption of the negative feedback loop that activate AKT upon mTORC1 inhibition. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 143-147 24327332-3 2014 Rapamycin is an immunomodulatory drug that targets the mammalian target of rapamycin pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 55-84 25482947-6 2014 We found that inhibitors of the mTOR pathway including rapamycin, wortmannin, and caffeine blunted the p53 response to nucleolar stress induced by actinomycin D. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 32-36 25597356-10 2014 Cells treated with rapamycin, an inhibitor of mTOR, displayed less expression of pRKIP after H. pylori infection. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 46-50 25104960-8 2014 We report the outcome of one patient with pretreated, progressing low grade metastatic ESS treated with medroxyprogesterone acetate in combination with the mTOR inhibitor sirolimus. Sirolimus 171-180 mechanistic target of rapamycin kinase Homo sapiens 156-160 24434865-3 2014 OBJECTIVE: Here, we investigate how different types of immunosuppressive therapy, namely the calcineurin inhibitors cyclosporin A and tacrolimus, as well as the mTOR inhibitor rapamycin, affect the function of immune cells in young and elderly persons. Sirolimus 176-185 mechanistic target of rapamycin kinase Homo sapiens 161-165 23530502-3 2014 Using rapamycin derivative (RAD001) as a prototype inhibitor, we aimed to systematically analyze the molecular mechanisms underlying the pleiotropic effects of mTOR signaling. Sirolimus 6-15 mechanistic target of rapamycin kinase Homo sapiens 160-164 24735369-16 2014 A newly synthesised dual inhibitor of PI3K and mTOR BEZ235 has been shown to be more effective than mTOR inhibitor rapamycin. Sirolimus 115-124 mechanistic target of rapamycin kinase Homo sapiens 47-51 24735369-16 2014 A newly synthesised dual inhibitor of PI3K and mTOR BEZ235 has been shown to be more effective than mTOR inhibitor rapamycin. Sirolimus 115-124 mechanistic target of rapamycin kinase Homo sapiens 100-104 24434958-8 2014 Further investigations are necessary to determine whether new drugs such as the mTOR inhibitor rapamycin may be effective for treatment of diffuse LM. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 80-84 26464852-8 2014 However, the inhibition of the mTOR pathway by rapamycin did not have a negative effect on p21 expression, suggesting that metformin regulates p21 upstream of mTOR. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 31-35 24756806-1 2014 Temsirolimus, an ester of sirolimus (rapamycin), selectively inhibits the kinase mammalian target of rapamycin (mTOR) and consequently blocks the translation of cell cycle regulatory proteins and prevents overexpression of angiogenic growth factors. Sirolimus 3-12 mechanistic target of rapamycin kinase Homo sapiens 81-110 24563652-4 2014 Lithium stimulates autophagy by decreasing the intracellular myo-inositol-1,4,5-triphosphate levels, while rapamycin acts through the inhibition of the mammalian target of rapamycin (mTOR). Sirolimus 107-116 mechanistic target of rapamycin kinase Homo sapiens 152-181 24563652-4 2014 Lithium stimulates autophagy by decreasing the intracellular myo-inositol-1,4,5-triphosphate levels, while rapamycin acts through the inhibition of the mammalian target of rapamycin (mTOR). Sirolimus 107-116 mechanistic target of rapamycin kinase Homo sapiens 183-187 24924131-6 2014 Moreover, here we demonstrate that SIRT3 expression is responsive to rapamycin, a small inhibitor of mammalian target of rapamycin that has been extensively employed as a caloric restriction mimetic. Sirolimus 69-78 mechanistic target of rapamycin kinase Homo sapiens 101-130 24072614-0 2014 LY294002 and Rapamycin promote coxsackievirus-induced cytopathic effect and apoptosis via inhibition of PI3K/AKT/mTOR signaling pathway. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 113-117 24587596-0 2014 Rapamycin attenuates endothelial apoptosis induced by low shear stress via mTOR and sestrin1 related redox regulation. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 75-79 24587596-3 2014 Since mTOR (mammalian target of rapamycin) pathway is involved in the antioxidative sestrins expression, we hypothesized that rapamycin attenuated low SS (LSS) induced endothelial dysfunction through mTOR and sestrin1 associated redox regulation. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 6-10 23956145-1 2014 BACKGROUND: The combination of vinblastine and mammalian target of rapamycin (mTOR) inhibitor sirolimus inhibits the growth of neuroblastoma xenografts through pro-apoptotic and anti-angiogenic mechanisms. Sirolimus 94-103 mechanistic target of rapamycin kinase Homo sapiens 47-76 23956145-1 2014 BACKGROUND: The combination of vinblastine and mammalian target of rapamycin (mTOR) inhibitor sirolimus inhibits the growth of neuroblastoma xenografts through pro-apoptotic and anti-angiogenic mechanisms. Sirolimus 94-103 mechanistic target of rapamycin kinase Homo sapiens 78-82 24756806-1 2014 Temsirolimus, an ester of sirolimus (rapamycin), selectively inhibits the kinase mammalian target of rapamycin (mTOR) and consequently blocks the translation of cell cycle regulatory proteins and prevents overexpression of angiogenic growth factors. Sirolimus 3-12 mechanistic target of rapamycin kinase Homo sapiens 112-116 24756806-1 2014 Temsirolimus, an ester of sirolimus (rapamycin), selectively inhibits the kinase mammalian target of rapamycin (mTOR) and consequently blocks the translation of cell cycle regulatory proteins and prevents overexpression of angiogenic growth factors. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 81-110 24756806-1 2014 Temsirolimus, an ester of sirolimus (rapamycin), selectively inhibits the kinase mammalian target of rapamycin (mTOR) and consequently blocks the translation of cell cycle regulatory proteins and prevents overexpression of angiogenic growth factors. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 112-116 24184927-3 2013 Using the MTOR inhibitor rapamycin we augmented colchicine"s myotoxic effect by increasing the autophagic flux; this resulted in an acute myopathy with muscle necrosis. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 10-14 24507028-3 2014 The drug sirolimus suppresses mTOR signaling but plays an uncertain role in the treatment of ADPKD. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 30-34 24189100-1 2013 Hyperactivation of mechanistic target of rapamycin (MTOR) is a common feature of human cancers, and MTOR inhibitors, such as rapamycin, are thus becoming therapeutics in targeting certain cancers. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 52-56 24189100-1 2013 Hyperactivation of mechanistic target of rapamycin (MTOR) is a common feature of human cancers, and MTOR inhibitors, such as rapamycin, are thus becoming therapeutics in targeting certain cancers. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 100-104 24012499-9 2013 This effect was attenuated by treatment with the pharmacological inhibitors U0126, LY294002 and rapamycin, which selectively block the activation of ERK1/2, Akt and mTOR, respectively, and siRNAs directed against ERK1/2, Akt and mTOR. Sirolimus 96-105 mechanistic target of rapamycin kinase Homo sapiens 165-169 23933173-5 2013 Rapamycin, an mTOR inhibitor, significantly suppressed ESC-positive NPC cell growth in vitro and tumor formation in vivo. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 24012499-9 2013 This effect was attenuated by treatment with the pharmacological inhibitors U0126, LY294002 and rapamycin, which selectively block the activation of ERK1/2, Akt and mTOR, respectively, and siRNAs directed against ERK1/2, Akt and mTOR. Sirolimus 96-105 mechanistic target of rapamycin kinase Homo sapiens 229-233 23689994-2 2013 Palomid 529, an investigational medication involving the immune Akt/mTOR pathway, is unique in dissociating both targets of rapamycin complexes TORC1 and TORC2. Sirolimus 124-133 mechanistic target of rapamycin kinase Homo sapiens 68-72 23968562-5 2013 Surprisingly, mTOR-inhibition enhanced the capacity of TLR-7-activated PDC to stimulate naive and memory T helper cell proliferation, which was caused by rapamycin-induced up-regulation of CD80 expression on PDC. Sirolimus 154-163 mechanistic target of rapamycin kinase Homo sapiens 14-18 24108520-6 2013 Rapamycin increased phosphorylation of raptor at Ser792 and decreased phosphorylation of rictor at Thr1135, suggesting that both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) are involved in GLT-1 expression. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 129-133 24108520-6 2013 Rapamycin increased phosphorylation of raptor at Ser792 and decreased phosphorylation of rictor at Thr1135, suggesting that both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) are involved in GLT-1 expression. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 145-149 23952610-2 2013 A large part of the immune response depends on the proliferation and clonal expansion of antigen-specific T cells, which depends on mTOR activation, and the pharmacological inhibition of this pathway by rapamycin is therefore potently immunosuppressive. Sirolimus 203-212 mechanistic target of rapamycin kinase Homo sapiens 132-136 24138944-1 2013 A phase I study utilizing decitabine (DAC) followed by the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, in patients with relapsed/refractory adult AML was undertaken to assess safety and feasibility. Sirolimus 79-88 mechanistic target of rapamycin kinase Homo sapiens 90-94 24314180-2 2013 We examined the involvement of the mammalian target of rapamycin (mTOR) signaling pathway in granulation formation and examined the effects of rapamycin. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 66-70 24067973-8 2013 We found that S6K was hyperphosphorylated in ANDV-infected, hypoxia-treated MECs and LECs and that rapamycin treatment for 1 h inhibited mTOR signaling responses and blocked permeability and giant cell formation in ANDV-infected monolayers. Sirolimus 99-108 mechanistic target of rapamycin kinase Homo sapiens 137-141 23911398-7 2013 Interestingly, the impaired memory CTL programming by wnt was partially rescued by mTOR inhibitor rapamycin. Sirolimus 98-107 mechanistic target of rapamycin kinase Homo sapiens 83-87 23911398-8 2013 In conclusion, we found that crosstalk between wnt and the IL-12 signaling inhibits T-bet and mTOR pathways and impairs memory programming which can be recovered in part by rapamycin. Sirolimus 173-182 mechanistic target of rapamycin kinase Homo sapiens 94-98 26824026-10 2013 We found that both rapamycin, a specific mTORC1 blocker, and PP242 a mTOR antagonist induce the arrest of myeloma cells irrespective of bortezomib sensitivity. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 41-45 24312355-5 2013 In studies with the mTOR inhibitor rapamycin, we have elucidated the stimulatory role of a mTOR-HIF-1alpha-VEGF axis in allergic response. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 20-24 24312355-5 2013 In studies with the mTOR inhibitor rapamycin, we have elucidated the stimulatory role of a mTOR-HIF-1alpha-VEGF axis in allergic response. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 91-95 24344117-8 2013 Mechanistic studies reveal that overexpression of FAM83D downregulates FBXW7 expression levels through a physical interaction, which results in elevated protein levels of oncogenic substrates downstream to FBXW7, such as mTOR, whose inhibition by rapamycin can suppress FAM83D-induced cell migration and invasion. Sirolimus 247-256 mechanistic target of rapamycin kinase Homo sapiens 221-225 24303008-7 2013 In support of this supposition, animals in which the mTOR/S6K1 intracellular pathway was blocked by chronic rapamycin treatment, rimonabant had no effect on ghrelin secretion. Sirolimus 108-117 mechanistic target of rapamycin kinase Homo sapiens 53-57 24260371-1 2013 Everolimus (EVL) and Sirolimus (SRL) are potent immunosuppressant agents belonging to the group of mammalian target of rapamycin (mTOR) inhibitors used to prevent transplant rejection. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 99-128 24049142-8 2013 Reactive oxygen species (ROS) increased by 32% after TGF-beta1 exposure for 48 h. TGF-beta activated the mammalian target of rapamycin (mTOR) pathway, and rapamycin reduced the TGF-beta1-stimulated increases in OCR, ECAR, ATP generation, cellular metabolic activity, and protein generation. Sirolimus 125-134 mechanistic target of rapamycin kinase Homo sapiens 136-140 24231729-4 2013 The mTOR inhibitor, rapamycin, reduced the viability of CD133(+) pancreatic cancer cells and sphere formation which is an index of self-renewal of stem-like cells, indicating that the mTOR pathway functions to maintain cancer stem-like cells. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 4-8 24231729-4 2013 The mTOR inhibitor, rapamycin, reduced the viability of CD133(+) pancreatic cancer cells and sphere formation which is an index of self-renewal of stem-like cells, indicating that the mTOR pathway functions to maintain cancer stem-like cells. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 184-188 24260371-1 2013 Everolimus (EVL) and Sirolimus (SRL) are potent immunosuppressant agents belonging to the group of mammalian target of rapamycin (mTOR) inhibitors used to prevent transplant rejection. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 130-134 24204783-1 2013 In an effort to circumvent resistance to rapamycin--an mTOR inhibitor--we searched for novel rapamycin-downstream-targets that may be key players in the response of cancer cells to therapy. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 55-59 24106124-2 2013 The purpose of this study was to examine the effects of rapamycin (an inhibitor of the mammalian target of rapamycin [mTOR] pathway) on myofibroblast formation in vitro and in-vivo. Sirolimus 56-65 mechanistic target of rapamycin kinase Homo sapiens 87-116 24106124-2 2013 The purpose of this study was to examine the effects of rapamycin (an inhibitor of the mammalian target of rapamycin [mTOR] pathway) on myofibroblast formation in vitro and in-vivo. Sirolimus 56-65 mechanistic target of rapamycin kinase Homo sapiens 118-122 24157830-8 2013 CONCLUSION: The mTOR inhibitor rapamycin significantly contributes to tumour growth inhibition and normalisation of the tumour vasculature through potent antiangiogenic effects. Sirolimus 31-40 mechanistic target of rapamycin kinase Homo sapiens 16-20 23932230-5 2013 Treatment of ARH-77 cells with the NF-kappaB inhibitor dimethyl fumarate or the mTOR inhibitor rapamycin suppressed NF-kappaB p65 nuclear translocation and enhanced the cytotoxic effect of melphalan. Sirolimus 95-104 mechanistic target of rapamycin kinase Homo sapiens 80-84 23316753-6 2013 As an inhibitor of the mammalian target of rapamycin (mTOR) pathway, the effective use of sirolimus may shed light on the emerging role of mTOR signaling in the development and pathogenesis of IHs. Sirolimus 90-99 mechanistic target of rapamycin kinase Homo sapiens 23-52 23316753-6 2013 As an inhibitor of the mammalian target of rapamycin (mTOR) pathway, the effective use of sirolimus may shed light on the emerging role of mTOR signaling in the development and pathogenesis of IHs. Sirolimus 90-99 mechanistic target of rapamycin kinase Homo sapiens 54-58 23316753-6 2013 As an inhibitor of the mammalian target of rapamycin (mTOR) pathway, the effective use of sirolimus may shed light on the emerging role of mTOR signaling in the development and pathogenesis of IHs. Sirolimus 90-99 mechanistic target of rapamycin kinase Homo sapiens 139-143 23792225-3 2013 The modest clinical anticancer activity of conventional mTOR allosteric inhibitors, rapamycin and its analogs (rapalogs), which preferentially inhibit mTORC1, in most types of cancer, has encouraged great efforts to develop mTOR kinase inhibitors (TORKinibs) that inhibit both mTORC1 and mTORC2, in the hope of developing a novel generation of mTOR inhibitors with better therapeutic efficacy than rapalogs. Sirolimus 84-93 mechanistic target of rapamycin kinase Homo sapiens 56-60 23792225-3 2013 The modest clinical anticancer activity of conventional mTOR allosteric inhibitors, rapamycin and its analogs (rapalogs), which preferentially inhibit mTORC1, in most types of cancer, has encouraged great efforts to develop mTOR kinase inhibitors (TORKinibs) that inhibit both mTORC1 and mTORC2, in the hope of developing a novel generation of mTOR inhibitors with better therapeutic efficacy than rapalogs. Sirolimus 84-93 mechanistic target of rapamycin kinase Homo sapiens 151-155 23792225-3 2013 The modest clinical anticancer activity of conventional mTOR allosteric inhibitors, rapamycin and its analogs (rapalogs), which preferentially inhibit mTORC1, in most types of cancer, has encouraged great efforts to develop mTOR kinase inhibitors (TORKinibs) that inhibit both mTORC1 and mTORC2, in the hope of developing a novel generation of mTOR inhibitors with better therapeutic efficacy than rapalogs. Sirolimus 84-93 mechanistic target of rapamycin kinase Homo sapiens 151-155 24159260-9 2013 CONCLUSION: To evaluate the financial consequence of adding mTOR inhibitors to the insurers" formulary, in the present study, a budget impact analysis was conducted on sirolimus. Sirolimus 168-177 mechanistic target of rapamycin kinase Homo sapiens 60-64 24205274-2 2013 Studies of signal transduction pathways leading to accelerated senescence have revealed that inhibition of mammalian target of rapamycin (mTOR) by rapamycin rescues cells from senescence. Sirolimus 127-136 mechanistic target of rapamycin kinase Homo sapiens 138-142 24205274-6 2013 Ly294002 (a phosphatidylinositol-3-kinase [PI3K] inhibitor) or rapamycin (an mTOR inhibitor) blocked the induction of cellular senescence markers suggesting roles for PI3K and mTOR. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 77-81 24205274-6 2013 Ly294002 (a phosphatidylinositol-3-kinase [PI3K] inhibitor) or rapamycin (an mTOR inhibitor) blocked the induction of cellular senescence markers suggesting roles for PI3K and mTOR. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 176-180 24012930-6 2013 Rapamycin, an inhibitor of mammalian target of rapamycin, evokes autophagy, as do capsaicin or thapsigargin, a sarco(endo)plasmic reticulum Ca(2+) ATPase inhibitor that causes Ca(2+) store depletion. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-56 24205354-6 2013 Quantitation of acidic vesicular organelles confirmed that combination of LC3 shRNA plasmid transfection and GST treatment prevented rapamycin-induced autophagy due to down regulation of autophagy promoting marker molecules (LC3 II, Beclin 1, TLR-4, and Myd88) and upregulation of autophagy inhibiting marker molecules (p62 and mTOR) in both cell lines. Sirolimus 133-142 mechanistic target of rapamycin kinase Homo sapiens 328-332 23580240-4 2013 Temsirolimus, an analog of the mTOR inhibitor rapamycin, is approved for the treatment of relapsed MCL. Sirolimus 46-55 mechanistic target of rapamycin kinase Homo sapiens 31-35 24030701-1 2013 PURPOSE: mTOR pathway hyperactivation occurs in approximately 90% of glioblastomas, but the allosteric mTOR inhibitor rapamycin has failed in the clinic. Sirolimus 118-127 mechanistic target of rapamycin kinase Homo sapiens 103-107 23636313-8 2013 Rituximab combined with rapamycin synergically downregulated the PI3K/AKT/mTOR signaling pathway. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 74-78 24099268-9 2013 injection of rapamycin - a specific inhibitor of mTOR - was observed to result in the reduction of spontaneous pain responses and the attenuation of unilateral thermal and bilateral mechanical hypersensitivity elicited by BmK I. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 49-53 23981724-1 2013 Clinical immunosuppression protocols use calcineurin inhibitors, such as cyclosporine A (CsA) or tacrolimus (FK506), or mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus (rapamycin). Sirolimus 177-186 mechanistic target of rapamycin kinase Homo sapiens 120-149 23553037-7 2013 Strikingly, combining anastrozole with the highly selective and allosteric Akt inhibitor MK-2206 or with the mTOR inhibitor rapamycin increased sensitivity to this AI in the control cells and was sufficient to overcome resistance and restore sensitivity to endocrine therapy in the resistant cells. Sirolimus 124-133 mechanistic target of rapamycin kinase Homo sapiens 109-113 23266287-8 2013 The inhibition of GSK-3beta phosphorylation and mTOR was achieved with LY294002 and rapamycin, respectively. Sirolimus 84-93 mechanistic target of rapamycin kinase Homo sapiens 48-52 23756767-4 2013 In a number of rodent models, the mTOR inhibitor rapamycin induces increased food intake, which is accompanied by increased body weight. Sirolimus 49-58 mechanistic target of rapamycin kinase Homo sapiens 34-38 24108003-7 2013 Interestingly, rapamycin, an inhibitor of MTOR, enhanced the expression of the autophagosomal marker LC3-II and GRP was localized within LC3-II-marked autophagosomes in vitro as well as in vivo, indicating autophagy-mediated degradation of GRP. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 42-46 23981724-1 2013 Clinical immunosuppression protocols use calcineurin inhibitors, such as cyclosporine A (CsA) or tacrolimus (FK506), or mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus (rapamycin). Sirolimus 140-149 mechanistic target of rapamycin kinase Homo sapiens 151-155 24044547-3 2013 As a result, mTOR inhibitors such as sirolimus and everolimus have the potential to provide targeted therapy for TSC patients. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 13-17 23773767-5 2013 This review explores the relevance of the mTOR pathway to epileptogenesis and its potential as a therapeutic target in epilepsy treatment by presenting the current results on mTOR inhibitors, in particular, rapamycin, in animal models of diverse types of epilepsy. Sirolimus 207-216 mechanistic target of rapamycin kinase Homo sapiens 42-46 23773767-5 2013 This review explores the relevance of the mTOR pathway to epileptogenesis and its potential as a therapeutic target in epilepsy treatment by presenting the current results on mTOR inhibitors, in particular, rapamycin, in animal models of diverse types of epilepsy. Sirolimus 207-216 mechanistic target of rapamycin kinase Homo sapiens 175-179 24023300-1 2013 BACKGROUND: Mammalian Target of Rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have been shown to reduce cutaneous carcinogenesis in organ-transplant recipients requiring for immunosuppressive treatment to prevent from allograft rejection. Sirolimus 69-78 mechanistic target of rapamycin kinase Homo sapiens 43-47 24265855-1 2013 Functional intracellular Ca(2+) signaling is essential for the upregulation of the canonical mTOR-controlled autophagy pathway triggered by rapamycin or by nutrient deprivation. Sirolimus 140-149 mechanistic target of rapamycin kinase Homo sapiens 93-97 24023300-1 2013 BACKGROUND: Mammalian Target of Rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have been shown to reduce cutaneous carcinogenesis in organ-transplant recipients requiring for immunosuppressive treatment to prevent from allograft rejection. Sirolimus 69-78 mechanistic target of rapamycin kinase Homo sapiens 12-41 23971829-4 2013 Ridaforolimus is a non-prodrug analog of rapamycin (sirolimus) with conserved affinity for mTOR but improved solubility, stability and bioavailability when compared with sirolimus. Sirolimus 41-50 mechanistic target of rapamycin kinase Homo sapiens 91-95 23971829-4 2013 Ridaforolimus is a non-prodrug analog of rapamycin (sirolimus) with conserved affinity for mTOR but improved solubility, stability and bioavailability when compared with sirolimus. Sirolimus 52-61 mechanistic target of rapamycin kinase Homo sapiens 91-95 23668915-3 2013 Yet AD, PD, HD and SCA3 are chronic degenerative diseases, and chronic administration of rapamycin at advanced clinical stages may result in deleterious systemic effects due to chronic inhibition of mammalian target of rapamycin (mTOR). Sirolimus 89-98 mechanistic target of rapamycin kinase Homo sapiens 199-228 23668915-3 2013 Yet AD, PD, HD and SCA3 are chronic degenerative diseases, and chronic administration of rapamycin at advanced clinical stages may result in deleterious systemic effects due to chronic inhibition of mammalian target of rapamycin (mTOR). Sirolimus 89-98 mechanistic target of rapamycin kinase Homo sapiens 230-234 24027431-7 2013 Rapamycin, an mTOR inhibitor, induces cell cycle arrest of PCa cells and enhances chemotherapeutic resistance of PCa cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 14-18 23161184-8 2013 Rapamycin, an inhibitor of mTOR, also reversed the effect of citrate in human umbilical vein endothelial cells and sprouting of aortic rings suggesting that the angiogenic effect of citrate involves activation of PI3K-Akt-mTOR pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 23161184-8 2013 Rapamycin, an inhibitor of mTOR, also reversed the effect of citrate in human umbilical vein endothelial cells and sprouting of aortic rings suggesting that the angiogenic effect of citrate involves activation of PI3K-Akt-mTOR pathway. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 222-226 23668243-3 2013 Studies on a number of ATP-competitive mTOR inhibitors have suggested that these inhibitors have a therapeutic superiority to rapalogs (rapamycin analogs) in a number of cancers. Sirolimus 136-145 mechanistic target of rapamycin kinase Homo sapiens 39-43 23991179-1 2013 Mammalian target of rapamycin complex 1 and 2 (mTORC1/2) are overactive in colorectal carcinomas; however, the first generation of mTOR inhibitors such as rapamycin have failed to show clinical benefits in treating colorectal carcinoma in part due to their effects only on mTORC1. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 47-51 23839048-2 2013 For rapamycin, this is achieved by inducing inhibitory ternary complexes with the kinase mTOR. Sirolimus 4-13 mechanistic target of rapamycin kinase Homo sapiens 89-93 23881200-6 2013 This Review describes the complex mTOR signaling pathways, which control vital cellular functions including mRNA translation, cell proliferation, cell growth, differentiation, angiogenesis, and apoptosis, and examines molecular mechanisms for rapamycin toxicity in beta-cells. Sirolimus 243-252 mechanistic target of rapamycin kinase Homo sapiens 34-38 23978644-2 2013 Sirolimus, an inhibitor of mTOR, has been reported to decrease the size of angiomyolipomas and stabilize pulmonary function in patients with LAM. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 24009772-5 2013 Additionally rapamycin, a known inhibitor of mTOR-dependent protein synthesis, rescued cells from metformin-induced apoptosis and down-regulated CHOP expression. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 45-49 23480027-2 2013 The aim of this study was to investigate the effect and mechanisms of sirolimus, an inhibitor of the mammalian target of rapamycin, on immune responses in a murine model of Crohn"s disease. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 101-130 23812052-8 2013 Increased understanding of the genetic cause of the disease and the underlying dysregulation of the mTOR pathway has led to clinical trials of mTOR inhibitors including sirolimus and everolimus. Sirolimus 169-178 mechanistic target of rapamycin kinase Homo sapiens 100-104 23835553-3 2013 Using a co-culture system of human lipopolysaccharide (LPS)-matured moDCs and allogeneic naive CD4(+) T cells, we show that inhibition of mTOR by the immunosuppressive drug rapamycin reduced moDC maturation and promoted Th2 skewing. Sirolimus 173-182 mechanistic target of rapamycin kinase Homo sapiens 138-142 23812052-8 2013 Increased understanding of the genetic cause of the disease and the underlying dysregulation of the mTOR pathway has led to clinical trials of mTOR inhibitors including sirolimus and everolimus. Sirolimus 169-178 mechanistic target of rapamycin kinase Homo sapiens 143-147 23879512-4 2013 The mTOR inhibitor sirolimus is reported to produce resolution of lymphatic abnormalities in LAM, but the efficiacy of the mTOR inhibitor everolimus has not been assessed. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 23702336-6 2013 Similar results were obtained by treatment with the mTOR inhibitor rapamycin. Sirolimus 67-76 mechanistic target of rapamycin kinase Homo sapiens 52-56 23884207-1 2013 Sirolimus is an inhibitor of mammalian target of rapamycin (mTOR) and is increasingly being used in transplantation and cancer therapies. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 29-58 23884207-1 2013 Sirolimus is an inhibitor of mammalian target of rapamycin (mTOR) and is increasingly being used in transplantation and cancer therapies. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 60-64 23722550-2 2013 The mTOR inhibitor rapamycin activates autophagy but paradoxically it also enhances radiosensitivity. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 23580233-9 2013 Moreover, the effect of Mono-Pt involved the AKT1-MTOR-RPS6KB1 pathway and MAPK1 (ERK2)/MAPK3 (ERK1) signaling, since the MTOR inhibitor rapamycin increased, while the MAPK1/3 inhibitor U0126 decreased Mono-Pt-induced autophagic cell death. Sirolimus 137-146 mechanistic target of rapamycin kinase Homo sapiens 122-126 22890326-4 2013 Rapamycin increases epidermal Akt1 phosphorylation via inhibition of the mTOR complex 1-dependent regulation of insulin receptor substrate-1. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 73-77 23395884-3 2013 Following the identification and characterization of mTOR-promoting activity in gliomagenesis, data from preclinical studies suggested the targeting of mTOR by rapamycin or its analogs (rapalogs) as a promising therapeutic approach. Sirolimus 160-169 mechanistic target of rapamycin kinase Homo sapiens 152-156 22890326-0 2013 The mTOR inhibitor rapamycin opposes carcinogenic changes to epidermal Akt1/PKBalpha isoform signaling. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 23478858-9 2013 Either systemic administration or intra-PFC infusion of the mTOR inhibitor rapamycin completely blocked the behavioral effects produced by PCMS in adolescence. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 60-64 26120590-5 2013 Interestingly, pharmacological activation of AMPK can prevent activation of mTOR/p70S6K and insulin resistance, while inhibition of mTOR with rapamycin prevents insulin resistance, but not AMPK downregulation. Sirolimus 142-151 mechanistic target of rapamycin kinase Homo sapiens 132-136 23619386-1 2013 Rapamycin is a canonical allosteric inhibitor of the mammalian tarpet of rapamycin (mTOR) kinase with immunosuppressive and proapoptotic activities. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 84-88 23499726-4 2013 A pilot trial in 16 ADPKD patients demonstrated that sirolimus, an mTOR inhibitor, reduced PLD volume by 26%. Sirolimus 53-62 mechanistic target of rapamycin kinase Homo sapiens 67-71 23730210-6 2013 Rapamycin alone inhibited mTOR signaling of all cancer cell lines tested in vitro and in vivo. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 26-30 23739000-5 2013 Preliminary studies in patients affected by tuberous sclerosis and treated with rapamycin or everolimus demonstrated potential benefits in seizure frequency reduction, suggesting that mTOR inhibition could be a promising treatment option for mTORopathies-related epilepsy. Sirolimus 80-89 mechanistic target of rapamycin kinase Homo sapiens 184-188 23532091-9 2013 Curcumin induced autophagy and apoptosis in SKN and SK-UT-1 cells, whereas rapamycin, a specific mTOR inhibitor, did not. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 97-101 23636418-1 2013 Rapamycin is a selective inhibitor of the mammalian target of rapamycin (mTOR), a regulator kinase that integrates growth factors signaling via the phosphoinositide-3-kinase pathway and that has emerged as a novel therapeutic modality in breast cancer (BC). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 42-71 23636418-1 2013 Rapamycin is a selective inhibitor of the mammalian target of rapamycin (mTOR), a regulator kinase that integrates growth factors signaling via the phosphoinositide-3-kinase pathway and that has emerged as a novel therapeutic modality in breast cancer (BC). Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 73-77 23578333-3 2013 Everolimus is a synthetic, orally available analogue of rapamycin that inhibits the activation of mTOR. Sirolimus 56-65 mechanistic target of rapamycin kinase Homo sapiens 98-102 23819061-4 2013 Rapamycin, an inhibitor of mTOR complex 1, reduced the level of HIF-1 alpha and blocked phosphorylation of ribosomal protein S6 kinase 1 (S6K), a transcriptional regulator of mTOR, demonstrating that hypoxia activates mTOR/S6K/HIF-1 alpha signaling in CCA. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 175-179 23730416-2 2013 The goal of this study was to compare the radiosensitizing activities of the allosteric mTOR inhibitor rapamycin with that of the competitive mTOR inhibitor PP242. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 88-92 23730416-3 2013 On the basis of immunoblot analyses, whereas rapamycin only partially inhibited mTOR complex 1 (mTORC1) activity and had no effect on mTOR complex 2 (mTORC2), PP242 inhibited the activity of both mTOR-containing complexes. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 80-84 23730416-3 2013 On the basis of immunoblot analyses, whereas rapamycin only partially inhibited mTOR complex 1 (mTORC1) activity and had no effect on mTOR complex 2 (mTORC2), PP242 inhibited the activity of both mTOR-containing complexes. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 96-100 23730416-3 2013 On the basis of immunoblot analyses, whereas rapamycin only partially inhibited mTOR complex 1 (mTORC1) activity and had no effect on mTOR complex 2 (mTORC2), PP242 inhibited the activity of both mTOR-containing complexes. Sirolimus 45-54 mechanistic target of rapamycin kinase Homo sapiens 96-100 23585566-1 2013 Previous evidence from post-mortem Alzheimer disease (AD) brains and drug (especially rapamycin)-oriented in vitro and in vivo models implicated an aberrant accumulation of the mammalian target of rapamycin (mTor) in tangle-bearing neurons in AD brains and its role in the formation of abnormally hyperphosphorylated tau. Sirolimus 86-95 mechanistic target of rapamycin kinase Homo sapiens 177-206 23585566-1 2013 Previous evidence from post-mortem Alzheimer disease (AD) brains and drug (especially rapamycin)-oriented in vitro and in vivo models implicated an aberrant accumulation of the mammalian target of rapamycin (mTor) in tangle-bearing neurons in AD brains and its role in the formation of abnormally hyperphosphorylated tau. Sirolimus 86-95 mechanistic target of rapamycin kinase Homo sapiens 208-212 23819061-4 2013 Rapamycin, an inhibitor of mTOR complex 1, reduced the level of HIF-1 alpha and blocked phosphorylation of ribosomal protein S6 kinase 1 (S6K), a transcriptional regulator of mTOR, demonstrating that hypoxia activates mTOR/S6K/HIF-1 alpha signaling in CCA. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 23819061-4 2013 Rapamycin, an inhibitor of mTOR complex 1, reduced the level of HIF-1 alpha and blocked phosphorylation of ribosomal protein S6 kinase 1 (S6K), a transcriptional regulator of mTOR, demonstrating that hypoxia activates mTOR/S6K/HIF-1 alpha signaling in CCA. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 175-179 23724051-9 2013 Unexpectedly, we found that pretreatment with rapamycin, a potent mTOR inhibitor, gradually (i) sensitized animals to KA treatment and (ii) induced gross anatomical changes in the brain. Sirolimus 46-55 mechanistic target of rapamycin kinase Homo sapiens 66-70 24252508-5 2013 This dysregulation of the mTOR downstream signaling cascade is not restricted to the brain but appears to be systemic and can be detected in peripheral lymphocytes as a reduced Rapamycin response. Sirolimus 177-186 mechanistic target of rapamycin kinase Homo sapiens 26-30 23663564-14 2013 Furthermore, the mTOR inhibitor, rapamycin, suppressed BCSCs in vitro and in vivo. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 17-21 23693095-7 2013 The in vitro and in vivo effect of the mTOR inhibitor rapamycin was also examined in human Hodgkin-lymphoma cell lines. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 39-43 23686371-5 2013 We observed an association between G6P accumulation, mTOR activation, endoplasmic reticulum (ER) stress, and impaired contractile function, all of which were prevented by pretreating animals with rapamycin (mTOR inhibition) or metformin (AMPK activation). Sirolimus 196-205 mechanistic target of rapamycin kinase Homo sapiens 53-57 24252508-6 2013 CONCLUSIONS: The dysfunction of the signaling pathways downstream of mTOR may represent a risk factor for Alzheimer"s disease and is independent of the ApoE status of the patients.We have also identified the molecular substrates of the beneficial effects of Rapamycin on the nervous system. Sirolimus 258-267 mechanistic target of rapamycin kinase Homo sapiens 69-73 23558291-5 2013 mTOR inhibition by rapamycin suppresses FBXW7 loss-driven EMT, invasion and stemness. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 0-4 23577651-2 2013 Furthermore, as mTOR is widely expressed, rapamycin (a macrolide antibiotic produced by Streptomyces hygroscopicus) is recommended in patients presenting neoplasia due to its antiproliferative actions. Sirolimus 42-51 mechanistic target of rapamycin kinase Homo sapiens 16-20 23403125-11 2013 The induction of S6K2/YY1 complex formation in response to serum stimulation is abolished by pre-treatment of cells with the mTOR inhibitor, rapamycin. Sirolimus 141-150 mechanistic target of rapamycin kinase Homo sapiens 125-129 23493289-2 2013 We investigated whether rapamycin, an inhibitor of the cell growth regulator mammalian target of rapamycin (mTOR) and effective against other SMC proliferative disorders, is of therapeutic benefit in experimental models of elastin deficiency. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 77-106 23493289-2 2013 We investigated whether rapamycin, an inhibitor of the cell growth regulator mammalian target of rapamycin (mTOR) and effective against other SMC proliferative disorders, is of therapeutic benefit in experimental models of elastin deficiency. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 108-112 23493289-4 2013 Increased mTOR signaling was detected in elastin-deficient aortas of newborn pups that was inhibited by maternal administration of rapamycin. Sirolimus 131-140 mechanistic target of rapamycin kinase Homo sapiens 10-14 23611130-0 2013 Rapamycin sensitizes glucocorticoid resistant acute lymphoblastic leukemia CEM-C1 cells to dexamethasone induced apoptosis through both mTOR suppression and up-regulation and activation of glucocorticoid receptor. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 136-140 23453973-6 2013 We then treated glucose-replete and -depleted cells with SB415286, U0126, LY294 and rapamycin to inhibit GSK3, MEK1/2, PI3K and mTOR, respectively. Sirolimus 84-93 mechanistic target of rapamycin kinase Homo sapiens 128-132 23557796-4 2013 This is supported by the findings that intracellular Ca(2+) chelator (BAPTA/AM) or mTOR inhibitor (rapamycin) abolished the events. Sirolimus 99-108 mechanistic target of rapamycin kinase Homo sapiens 83-87 23395818-5 2013 Rapamycin effectively inhibits mTOR in all phases of CML, but does not reduce number of LSC-enriched CD34(+) blast crisis (BC) cells, neither alone nor in combination with imatinib in CML-BC cells. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 31-35 23595747-8 2013 Axonal application of LY294002, a phosphoinositide3-kinase inhibitor, or rapamycin, an mTOR inhibitor, abolished axonal outgrowth enhanced by overexpression of the miR-17-92 cluster. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 87-91 23548622-1 2013 PURPOSE: To investigate the safety and effects of subconjunctival sirolimus, an mTOR inhibitor and immunosuppressive agent, for the treatment of geographic atrophy (GA). Sirolimus 66-75 mechanistic target of rapamycin kinase Homo sapiens 80-84 23601105-2 2013 Switching from cyclosporine to the mTOR inhibitor rapamycin is reported to promote KS regression without allograft rejection. Sirolimus 50-59 mechanistic target of rapamycin kinase Homo sapiens 35-39 23601105-3 2013 Examining the underlying molecular basis for this clinical observation, we find that KSHV infection selectively upregulates mTOR signaling in primary human lymphatic endothelial cells (LECs), but not blood endothelial cells (BECs), and sensitizes LECs to rapamycin-induced apoptosis. Sirolimus 255-264 mechanistic target of rapamycin kinase Homo sapiens 124-128 23591341-9 2013 Cisplatin treatment inhibited the phosphorylation of mTOR/P70S6K, which was most significant at the concentration of 100 mumol/L for 48 h. Cisplatin also induced cell viability loss, which was 12% and 45% at the concentrations of 50, and 100 mumol/L for 24 h. This effect could be enhanced by rapamycin (F=74.890,P<0.01). Sirolimus 293-302 mechanistic target of rapamycin kinase Homo sapiens 53-57 23274896-8 2013 The mammalian target of rapamycin (mTOR) kinase inhibitor Torin1 mimicked the rapamycin effects on autophagy and stress, indicating that the beneficial effects of rapamycin are indeed mediated via inhibition of mTOR. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 35-39 23416162-8 2013 When treated with the PI3K/AKT/mTOR pathway inhibitor rapamycin alone or in combination with the multikinase inhibitor sorafenib, all xenografts responded with increased lipid content and a more differentiated gene expression profile. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 31-35 23274896-8 2013 The mammalian target of rapamycin (mTOR) kinase inhibitor Torin1 mimicked the rapamycin effects on autophagy and stress, indicating that the beneficial effects of rapamycin are indeed mediated via inhibition of mTOR. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 211-215 23479645-9 2013 Application of the mTOR inhibitor rapamycin prevented post-hypoxic seizure impairment of homeostasis, suggesting that homeostatic plasticity mechanisms may be potentially modifiable therapeutic targets in epileptogenesis. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 19-23 23512499-9 2013 As with rapamycin, cardamonin inhibited the activity of the mammalian target of rapamycin and S6 kinase 1, decreased the Ser 636/639 phosphorylation of insulin receptor substrate-1 and increased the activation of protein kinase B. Sirolimus 8-17 mechanistic target of rapamycin kinase Homo sapiens 60-89 22927055-4 2013 Preliminary reports have indicated that the mTOR inhibitors sirolimus and related drugs have activity in some patients with non-TSC-associated PEComa. Sirolimus 60-69 mechanistic target of rapamycin kinase Homo sapiens 44-48 23312829-3 2013 Everolimus, a rapamycin derivative, inhibits the mTOR pathway by acting on the mTOR complex 1. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 49-53 23662044-2 2013 Rapamycin (RPM), a specific inhibitor of mTOR, exhibits potent and broad in vitro and in vivo antitumor activity against leukemia, breast cancer, and melanoma. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 41-45 23662044-2 2013 Rapamycin (RPM), a specific inhibitor of mTOR, exhibits potent and broad in vitro and in vivo antitumor activity against leukemia, breast cancer, and melanoma. Sirolimus 11-14 mechanistic target of rapamycin kinase Homo sapiens 41-45 23555162-7 2013 Additionally, involvement of the phosphatidylinositol-3 kinase (PI3K)/Akt/mammalian target of the rapamycin (mTOR) pathway was also detected by Western blotting. Sirolimus 98-107 mechanistic target of rapamycin kinase Homo sapiens 109-113 23312829-3 2013 Everolimus, a rapamycin derivative, inhibits the mTOR pathway by acting on the mTOR complex 1. Sirolimus 14-23 mechanistic target of rapamycin kinase Homo sapiens 79-83 23297825-2 2013 The mammalian target of rapamycin complex 1 (mTORC1) is rapamycin-sensitive and mediates temporal control of cell growth by regulating several cellular processes, such as translation, transcription, and nutrient transport while the mammalian target of rapamycin complex 2 (mTORC2) is in sensitive to rapamycin and is involved in spatial control of cell growth via cytoskeleton regulation. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 232-261 23644232-6 2013 mTOR inhibitors, such as rapamycin and its analogs, may represent novel, rational therapies for a variety of neurological disorders. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 0-4 23395931-11 2013 Inhibition of mTOR with rapamycin decreased NF-kappaB activation resulting in increased Bnip3 expression and cell death. Sirolimus 24-33 mechanistic target of rapamycin kinase Homo sapiens 14-18 23482748-0 2013 Comparative effects of PP242 and rapamycin on mTOR signalling and NOTCH signalling in leukemia cells. Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 46-50 23252795-2 2013 The importance of mTOR in health and diseases has fueled the development of molecules that inhibit mTOR signaling, including rapalogs (sirolimus, temsirolimus, everolimus and deforolimus), which complex with FK506-binding protein 12 (FK-BP12) to inhibit mTOR complex 1 (MTORC1) activity in an allosteric manner, or the more recent ATP-competitive mTOR inhibitors (mTORi), which target the catalytic site of the enzyme. Sirolimus 135-144 mechanistic target of rapamycin kinase Homo sapiens 99-103 23252795-2 2013 The importance of mTOR in health and diseases has fueled the development of molecules that inhibit mTOR signaling, including rapalogs (sirolimus, temsirolimus, everolimus and deforolimus), which complex with FK506-binding protein 12 (FK-BP12) to inhibit mTOR complex 1 (MTORC1) activity in an allosteric manner, or the more recent ATP-competitive mTOR inhibitors (mTORi), which target the catalytic site of the enzyme. Sirolimus 135-144 mechanistic target of rapamycin kinase Homo sapiens 99-103 23252795-2 2013 The importance of mTOR in health and diseases has fueled the development of molecules that inhibit mTOR signaling, including rapalogs (sirolimus, temsirolimus, everolimus and deforolimus), which complex with FK506-binding protein 12 (FK-BP12) to inhibit mTOR complex 1 (MTORC1) activity in an allosteric manner, or the more recent ATP-competitive mTOR inhibitors (mTORi), which target the catalytic site of the enzyme. Sirolimus 135-144 mechanistic target of rapamycin kinase Homo sapiens 99-103 23328844-9 2013 The impact of TGF-beta/Smad3 signals on T-cell activation was similar to that of the mTOR inhibitor Rapamycin. Sirolimus 100-109 mechanistic target of rapamycin kinase Homo sapiens 85-89 23044764-7 2013 Therefore, the inhibition of mTOR kinase activity in glial cells results in anti-inflammatory actions, suggesting possible beneficial effects of mTOR inhibitors (like rapamycin) in the treatment of inflammatory-based pathologies of the central nervous system. Sirolimus 167-176 mechanistic target of rapamycin kinase Homo sapiens 29-33 23044764-7 2013 Therefore, the inhibition of mTOR kinase activity in glial cells results in anti-inflammatory actions, suggesting possible beneficial effects of mTOR inhibitors (like rapamycin) in the treatment of inflammatory-based pathologies of the central nervous system. Sirolimus 167-176 mechanistic target of rapamycin kinase Homo sapiens 145-149 23283642-0 2013 Disruption of an hTERT-mTOR-RAPTOR protein complex by a phytochemical perillyl alcohol and rapamycin. Sirolimus 91-100 mechanistic target of rapamycin kinase Homo sapiens 23-27 23283642-1 2013 We previously demonstrated in prostate cancer cells that a phytochemical-perillyl alcohol-and the mechanistic target of rapamycin (mTOR) inhibitor rapamycin rapidly attenuated telomerase activity. Sirolimus 120-129 mechanistic target of rapamycin kinase Homo sapiens 131-135 23283642-7 2013 Perillyl alcohol or rapamycin caused rapid dissociation of the captured hTERT-mTOR-RAPTOR complex, establishing an additional mechanism by which these agents decrease telomerase activity. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 78-82 23555298-4 2013 Expectedly, our subjects exhibited a marked range of hypertrophic responses (3% to +28%), and when applying Ingenuity Pathway Analysis (IPA) up-stream analysis to ~580 genes that co-varied with gain in lean mass, we identified rapamycin (mTOR) signaling associating with growth (P = 1.4 x 10(-30)). Sirolimus 227-236 mechanistic target of rapamycin kinase Homo sapiens 238-242 23426399-2 2013 For in vitro experiments, NCI-H358, a human lung adenocarcinoma cell line, was co-cultured with immortalized astrocytes, and treated with rapamycin, an mTOR inhibitor. Sirolimus 138-147 mechanistic target of rapamycin kinase Homo sapiens 152-156 23446718-8 2013 Antagonism of the mTOR pathway with rapamycin and everolimus may provide new therapeutic options for these TSC patients. Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 18-22 23879996-8 2013 RT-PCR showed that the expression of mTOR mRNA was lower in OSCs treated with 100 nmol/L rapamycin (0.961 +- 0.060) than that with 0 nmol/L rapamycin (1.654 +- 0.246, P < 0.05). Sirolimus 89-98 mechanistic target of rapamycin kinase Homo sapiens 37-41 23879996-8 2013 RT-PCR showed that the expression of mTOR mRNA was lower in OSCs treated with 100 nmol/L rapamycin (0.961 +- 0.060) than that with 0 nmol/L rapamycin (1.654 +- 0.246, P < 0.05). Sirolimus 140-149 mechanistic target of rapamycin kinase Homo sapiens 37-41 23364979-5 2013 Furthermore, we also found that TGF-beta1-induced mTOR and p70S6K phosphorylation were significantly down-regulated by rapamycin. Sirolimus 119-128 mechanistic target of rapamycin kinase Homo sapiens 50-54 23364979-7 2013 CONCLUSION: These results indicate that rapamycin effectively suppresses TGF-beta1-induced type III collagen and fibronectin levels in primary human lung fibroblasts partly through the mTOR/p70S6K pathway. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 185-189 23370361-10 2013 Pristimerin inhibited migration and invasion of cells, and co-treatment with the mTOR inhibitor rapamycin additionally suppressed these activities. Sirolimus 96-105 mechanistic target of rapamycin kinase Homo sapiens 81-85 23261661-2 2013 Rapamycin is a powerful mTOR inhibitor and strong autophagy inducer. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 24-28 23361299-6 2013 Using an ex vivo platform, we identified putative responders to rapamycin, an mTOR inhibitor in these tumors. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 78-82 22930581-5 2013 We proposed that the use of dual inhibitors of PI3K and mTOR could be a promising approach to more efficiently inhibit the PI3K/Akt pathway than rapamycin or PI3K inhibitor alone and produce better treatment outcome. Sirolimus 145-154 mechanistic target of rapamycin kinase Homo sapiens 56-60 23222818-11 2013 Furthermore, the mTOR inhibitor sirolimus strongly inhibited alloresponses in vitro, whereas it did not affect CMV-specific responses. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 17-21 23393364-1 2013 BACKGROUND: Sirolimus is a potent blocker of mammalian target of Rapamycin (MTOR), with anti proliferative activity. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 45-74 23393364-1 2013 BACKGROUND: Sirolimus is a potent blocker of mammalian target of Rapamycin (MTOR), with anti proliferative activity. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 76-80 23079231-0 2013 Synergistic immunosuppressive effects of the mTOR inhibitor sirolimus and the phytochemical curcumin. Sirolimus 60-69 mechanistic target of rapamycin kinase Homo sapiens 45-49 23079231-2 2013 Whereas the antiproliferative effect of sirolimus is mainly mediated by inhibition of mTOR, curcumin is described to affect many molecular targets which makes it unpredictable to appraise if the effects of these both substances on cell proliferation and especially on immunosuppression are additive or synergistic. Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 86-90 22762560-3 2013 By doing so, rapamycin interferes with the phosphoinositide 3-kinase (PI3K)-Akt-mTOR axis that controls several cellular functions involving cell growth, proliferation and angiogenesis. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 80-84 23555865-4 2013 The mTOR inhibitor, Rapamycin, stabilizes lung function in LAM and decreases the volume of renal angiomyolipomas, but lung function declines and angiomyolipomas regrow when treatment is discontinued, suggesting that factors induced by mTORC1 inhibition may promote the survival of TSC2-deficient cells. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 4-8 24319682-4 2013 The noncoding RNA growth arrest specific transcript 5 (GAS5) has recently been shown to play a key role in growth arrest induced by several mechanisms, including serum withdrawal and treatment with the mTOR inhibitor rapamycin. Sirolimus 217-226 mechanistic target of rapamycin kinase Homo sapiens 202-206 23492649-3 2013 Several mTOR inhibitors (sirolimus, everolimus, temsirolimus, and ridaforolimus) have demonstrated antitumor activity in breast cancer cells. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 8-12 24151517-1 2013 The mammalian target of rapamycin inhibitors (mTOR-I), sirolimus and everolimus, are immunosuppressive drugs largely used in renal transplantation. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 4-33 24151517-1 2013 The mammalian target of rapamycin inhibitors (mTOR-I), sirolimus and everolimus, are immunosuppressive drugs largely used in renal transplantation. Sirolimus 55-64 mechanistic target of rapamycin kinase Homo sapiens 46-50 23259423-2 2013 mTOR inhibitors, such as sirolimus (SRL), display immunosuppressive and antiproliferative properties, and the use of SRL in kidney transplant recipients reduces the risk of post-transplant cancer. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 0-4 24093774-3 2013 However, the dual nature of mTOR, existing in two multiprotein complexes mTORC1 and mTORC2 driven by different feedback loops, decreases the therapeutic effects of rapamycin, the specific mTOR inhibitor. Sirolimus 164-173 mechanistic target of rapamycin kinase Homo sapiens 28-32 24093774-3 2013 However, the dual nature of mTOR, existing in two multiprotein complexes mTORC1 and mTORC2 driven by different feedback loops, decreases the therapeutic effects of rapamycin, the specific mTOR inhibitor. Sirolimus 164-173 mechanistic target of rapamycin kinase Homo sapiens 73-77 22711601-5 2013 An mTOR inhibitor, rapamycin, suppressed lactic acid production in lymphoma cell line cultures and also diminished steady-state lactate levels in xenotransplants. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 3-7 23879172-3 2013 Phosphorus-containing sirolimus (FIM-A), which targets mTOR signaling, inhibits cancer cell growth in vitro. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 55-59 23116613-8 2013 This effect was abated by pathway blockers: the AMPK activator AICAR and the mTOR inhibitor rapamycin. Sirolimus 92-101 mechanistic target of rapamycin kinase Homo sapiens 77-81 23560047-7 2013 Rapamycin, an inhibitor of mTOR signalling, previously observed to prevent bladder strain induced de-differentiation of fully differentiated smooth muscle cells in vitro, inhibits FBS-induced smooth muscle cell differentiation of undifferentiated SKPs. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 23117620-4 2013 The dephosphorylating activity of ferulic acid was almost comparable to that of rapamycin, an established mTor inhibitor (TORC1). Sirolimus 80-89 mechanistic target of rapamycin kinase Homo sapiens 106-110 22234876-2 2013 However, mammalian target of rapamycin inhibitors (e.g., sirolimus; SRL) appear to be more immunoregulatory and might promote a tolerant state for withdrawal. Sirolimus 57-66 mechanistic target of rapamycin kinase Homo sapiens 9-38 23439391-1 2013 Rapamycin (sirolimus) is a fungal fermentation product that inhibits the proper functioning of a serine/threonine protein kinase in mammalian cells eponymously named mammalian target of rapamycin, or mTOR. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 166-195 23439391-1 2013 Rapamycin (sirolimus) is a fungal fermentation product that inhibits the proper functioning of a serine/threonine protein kinase in mammalian cells eponymously named mammalian target of rapamycin, or mTOR. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 200-204 23439391-1 2013 Rapamycin (sirolimus) is a fungal fermentation product that inhibits the proper functioning of a serine/threonine protein kinase in mammalian cells eponymously named mammalian target of rapamycin, or mTOR. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 166-195 23439391-1 2013 Rapamycin (sirolimus) is a fungal fermentation product that inhibits the proper functioning of a serine/threonine protein kinase in mammalian cells eponymously named mammalian target of rapamycin, or mTOR. Sirolimus 11-20 mechanistic target of rapamycin kinase Homo sapiens 200-204 23712219-1 2013 INTRODUCTION: mTOR (mammalian target of rapamycin) inhibitors sirolimus and everolimus, used as immunosuppressants in solid organ transplantation, may cause severe adverse effects, such as interstitial pneumonitis. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 14-18 23712219-1 2013 INTRODUCTION: mTOR (mammalian target of rapamycin) inhibitors sirolimus and everolimus, used as immunosuppressants in solid organ transplantation, may cause severe adverse effects, such as interstitial pneumonitis. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 20-49 23565163-3 2013 The phosphorylation is inhibited by rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR) in complex with raptor (mTORC1). Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 71-100 23565163-3 2013 The phosphorylation is inhibited by rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR) in complex with raptor (mTORC1). Sirolimus 36-45 mechanistic target of rapamycin kinase Homo sapiens 102-106 23887441-1 2012 Sirolimus, the prototypical inhibitor of the mammalian target of rapamycin, has substantial antitumor activity. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 45-74 23536771-9 2013 Rapamycin decreased the SE-induced mTOR activation and attenuated microgliosis which was mostly localized within the CA1 area. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 35-39 22875481-8 2013 Moreover, inhibition of mTOR by rapamycin reversed the antidepressant effects of ketamine. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 24-28 23127854-9 2012 Moreover, the exacerbation of OA-induced events by rapamycin suggests that mTOR and PP2A work in concert to regulate cell survival, activated Akt and the levels of ubiquitinated proteins. Sirolimus 51-60 mechanistic target of rapamycin kinase Homo sapiens 75-79 22902509-3 2012 However, mTOR inhibition with rapamycin analogs or kinase inhibitors reduces cell growth but does not induce apoptosis, and the clinical benefit of rapamycin analogs has been modest. Sirolimus 30-39 mechanistic target of rapamycin kinase Homo sapiens 9-13 23271044-3 2012 Preclinical data also suggest that allosteric mTOR inhibition with rapamycin impaired leukemia initiating cells (LICs) function. Sirolimus 67-76 mechanistic target of rapamycin kinase Homo sapiens 46-50 22921929-7 2012 In addition, the sustained effect of MPEP in the NSF test was partially abolished by pretreatment with a mammalian target of rapamycin (mTOR) antagonist, rapamycin. Sirolimus 125-134 mechanistic target of rapamycin kinase Homo sapiens 136-140 23089982-5 2012 Interestingly, despite apparent inactivation of the PI3K/AKT signaling pathway, resistant cells exhibited constitutive activation of mammalian target of rapamycin complex 1 (mTORC1) and were highly sensitive to mTOR inhibition with rapamycin and the dual PI3K/mTOR inhibitor NVP-BEZ235. Sirolimus 153-162 mechanistic target of rapamycin kinase Homo sapiens 174-178 23089982-5 2012 Interestingly, despite apparent inactivation of the PI3K/AKT signaling pathway, resistant cells exhibited constitutive activation of mammalian target of rapamycin complex 1 (mTORC1) and were highly sensitive to mTOR inhibition with rapamycin and the dual PI3K/mTOR inhibitor NVP-BEZ235. Sirolimus 153-162 mechanistic target of rapamycin kinase Homo sapiens 211-215 22983984-5 2012 We also investigated changes in sensitivity to the mTOR inhibitor, rapamycin, in inhibitor miR-144-transfected cells. Sirolimus 67-76 mechanistic target of rapamycin kinase Homo sapiens 51-55 23730262-3 2012 As a result, mTOR inhibitors such as sirolimus and everolimus have the potential to provide targeted therapy for patients with TSC. Sirolimus 37-46 mechanistic target of rapamycin kinase Homo sapiens 13-17 23136410-2 2012 Although hyperactivation of mTOR has been strongly linked to the development of epilepsy and, conversely, inhibition of mTOR by rapamycin treatment is protective against seizures in several models, the downstream epileptic mechanisms have remained elusive. Sirolimus 128-137 mechanistic target of rapamycin kinase Homo sapiens 120-124 23215723-8 2012 In preclinical settings, dual PI3K/mTOR inhibitors displayed a much stronger cytotoxicity against leukemic cells than either PI3K inhibitors or allosteric mTOR inhibitors, such as rapamycin and its derivatives (rapalogs). Sirolimus 180-189 mechanistic target of rapamycin kinase Homo sapiens 35-39 23762622-5 2012 mTOR inhibitors, such as rapamycin and its derivatives temsirolimus and everolimus, exhibit inhibitory effects on head and neck cancer in both in vitro cell line model and in vivo xenograft model. Sirolimus 25-34 mechanistic target of rapamycin kinase Homo sapiens 0-4 22917563-5 2012 Transfection of SH-SY5Y cells with AMPK or LC3beta shRNA, as well as treatment with pharmacological autophagy inhibitors suppressed, while mTOR inhibitor rapamycin potentiated 6-OHDA-induced oxidative stress and apoptotic cell death. Sirolimus 154-163 mechanistic target of rapamycin kinase Homo sapiens 139-143 22895070-8 2012 Proliferative inhibition correlated loosely with the presence of activating PIK3CA mutations and was strengthened in combination with the mTOR inhibitor rapamycin. Sirolimus 153-162 mechanistic target of rapamycin kinase Homo sapiens 138-142 22689083-6 2012 Activation of autophagy with rapamycin resulted in increased wogonin-mediated autophagy via inhibition of mTOR/P70S6K pathway. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 106-110 23053656-8 2012 Subsequent studies revealed that NDGA may also direct target mTORC1 complex because NDGA suppressed amino acids- and insulin-stimulated mTORC1 and acted like rapamycin to disrupt mTOR-Raptor interaction. Sirolimus 158-167 mechanistic target of rapamycin kinase Homo sapiens 61-65 22307455-0 2012 Remarkable inhibition of mTOR signaling by the combination of rapamycin and 1,4-phenylenebis(methylene)selenocyanate in human prostate cancer cells. Sirolimus 62-71 mechanistic target of rapamycin kinase Homo sapiens 25-29 24710534-5 2012 mTOR inhibition via rapamycin decreases TAZ levels in HepG2 but not MCF7 cells and increases TEAD1 levels in MCF7 but not HepG2 cells, suggesting a selective role of the mTOR pathway in regulating these Hippo targets in a cell type-specific manner. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 0-4 22995302-10 2012 The mTOR inhibitor, rapamycin, abolishes Sirtinol-induced inflammation and NF-kappaB activation associated with p62/Sqstm1 accumulation. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 4-8 23342262-5 2012 In vitro studies prove that while Sirolimus (25 nmol/L) affects the signal downstream to mammalian target of rapamycin (mTOR), Nimotuzumab (83 nmol/L) downregulates pTYR, pMAPK and pSTAT3 by 40%, 20% and 30%, respectively. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 89-118 22913509-0 2012 Preventive and therapeutic effects of rapamycin, a mammalian target of rapamycin inhibitor, on food allergy in mice. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 51-80 23342262-5 2012 In vitro studies prove that while Sirolimus (25 nmol/L) affects the signal downstream to mammalian target of rapamycin (mTOR), Nimotuzumab (83 nmol/L) downregulates pTYR, pMAPK and pSTAT3 by 40%, 20% and 30%, respectively. Sirolimus 34-43 mechanistic target of rapamycin kinase Homo sapiens 120-124 22992293-6 2012 These effects were intensified by combined treatment of AST with the mTOR inhibitor rapamycin. Sirolimus 84-93 mechanistic target of rapamycin kinase Homo sapiens 69-73 23027611-5 2012 Linking this signalling event to cognitive impairment, the mTOR inhibitor rapamycin prevented deficits in social cognition and novel object discrimination induced by 5-HT(6) agonists. Sirolimus 74-83 mechanistic target of rapamycin kinase Homo sapiens 59-63 22863900-1 2012 BACKGROUND: The mammalian target of rapamycin (m-TOR) inhibitor sirolimus is an immunosuppressive drug used in kidney transplantation. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 16-45 23384908-3 2012 The expressions of mTOR, 4E-BP1 and p70S6K at protein and mRNA level in K562 cells with rapamycin treatment were detected by Western blot and RT-PCR. Sirolimus 88-97 mechanistic target of rapamycin kinase Homo sapiens 19-23 23384908-8 2012 The phosphorylation of mTOR was decreased after rapamycin treatment, as well as the expressions of 4E-BP1 and p70S6K at protein and mRNA level (P < 0.05). Sirolimus 48-57 mechanistic target of rapamycin kinase Homo sapiens 23-27 22941182-4 2012 When mammalian target of rapamycin (mTOR) inhibitors (sirolimus, everolimus) became available, these findings were observed increasingly, particularly in direct comparisons with inosine 5"-monophosphate dehydrogenase inhibitors. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 5-34 22941182-4 2012 When mammalian target of rapamycin (mTOR) inhibitors (sirolimus, everolimus) became available, these findings were observed increasingly, particularly in direct comparisons with inosine 5"-monophosphate dehydrogenase inhibitors. Sirolimus 54-63 mechanistic target of rapamycin kinase Homo sapiens 36-40 22840496-7 2012 RESULTS: We observed that IL-22 induced significant proliferation of NHEK and FLS which was effectively inhibited by dual kinase (PI3K/mTOR) inhibitor, NVP-BEZ235 and specific mTOR inhibitor, Rapamycin. Sirolimus 192-201 mechanistic target of rapamycin kinase Homo sapiens 176-180 22840496-8 2012 In NHEK and FLS, IL-22 significantly induced phosphorylation of Akt and mTOR which was effectively blocked by Rapamycin and NVP-BEZ235. Sirolimus 110-119 mechanistic target of rapamycin kinase Homo sapiens 72-76 22285179-4 2012 Moreover, rapamycin inhibited AKT/mTOR signalling by dephosphorylation of the downstream target p70S6 kinase (p70S6K). Sirolimus 10-19 mechanistic target of rapamycin kinase Homo sapiens 34-38 22285179-8 2012 In conclusion, we demonstrate that rapamycin effectively inhibits HB growth both in vitro and in vivo by blocking AKT/mTOR signalling at the level of p70S6K and that rapamycin should be considered to treat HB patients especially those to be indicated for liver transplantation to benefit from its anti-tumourigenic and immunosuppressive properties. Sirolimus 35-44 mechanistic target of rapamycin kinase Homo sapiens 118-122 23369601-4 2012 RAPA-DC are generated through inhibition of the integrative kinase mammalian target of rapamycin (mTOR) by the immunosuppressive macrolide rapamycin during propagation of monocyte-derived DC. Sirolimus 87-96 mechanistic target of rapamycin kinase Homo sapiens 98-102 22973301-1 2012 Rapamycin, an inhibitor of mTOR complex 1 (mTORC1), improves insulin sensitivity in acute studies in vitro and in vivo by disrupting a negative feedback loop mediated by S6 kinase. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 22932872-3 2012 We have tested the therapeutic potential of rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR) and three other autophagy activators (spermidine, carbamazepine, and tamoxifen) in a FTLD-U mouse model with TDP-43 proteinopathies. Sirolimus 44-53 mechanistic target of rapamycin kinase Homo sapiens 75-104 22932872-3 2012 We have tested the therapeutic potential of rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR) and three other autophagy activators (spermidine, carbamazepine, and tamoxifen) in a FTLD-U mouse model with TDP-43 proteinopathies. Sirolimus 44-53 mechanistic target of rapamycin kinase Homo sapiens 106-110 22973301-2 2012 We find that rapamycin has a clear biphasic effect on insulin sensitivity in C2C12 myotubes, with enhanced responsiveness during the first hour that declines to almost complete insulin resistance by 24-48 h. We and others have recently observed that chronic rapamycin treatment induces insulin resistance in rodents, at least in part due to disruption of mTORC2, an mTOR-containing complex that is not acutely sensitive to the drug. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 355-359 22973301-8 2012 Thus, mTORC2 disruption, rather than inhibition of mitochondria, causes insulin resistance in rapamycin-treated myotubes, and this system may serve as a useful model to understand the effects of rapamycin on mTOR signaling in vivo. Sirolimus 94-103 mechanistic target of rapamycin kinase Homo sapiens 6-10 22759736-8 2012 Kaposi"s sarcoma may regress with the use of the mammalian target of rapamycin inhibitor sirolimus. Sirolimus 89-98 mechanistic target of rapamycin kinase Homo sapiens 49-78 22842983-2 2012 While rapamycin and its derivatives (e.g., everolimus) have been shown to inhibit mTOR signaling and cell proliferation in preclinical models of breast cancer, mTOR inhibition has demonstrated variable clinical efficacy with a trend toward better responses in estrogen receptor alpha positive (ERalpha+) compared to ERalpha negative (ERalpha-) tumors. Sirolimus 6-15 mechanistic target of rapamycin kinase Homo sapiens 82-86 22842983-5 2012 We investigated the effect of rapamycin on the growth of several ERalpha+ and ERalpha- breast cancer cell lines and examined differences in the phosphorylation of mTOR substrates (SGK1, p70S6K, and Akt) that might account for the differing sensitivity of these cell lines to rapamycin. Sirolimus 275-284 mechanistic target of rapamycin kinase Homo sapiens 163-167 22613737-3 2012 Because the mammalian target of rapamycin (mTOR) pathway regulates neurite outgrowth, synaptic plasticity and cell survival, thereby influencing brain development, we tested if exposure of the immature brain to the mTOR inhibitor rapamycin changes seizure susceptibility to neurological insults. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 43-47 22613737-3 2012 Because the mammalian target of rapamycin (mTOR) pathway regulates neurite outgrowth, synaptic plasticity and cell survival, thereby influencing brain development, we tested if exposure of the immature brain to the mTOR inhibitor rapamycin changes seizure susceptibility to neurological insults. Sirolimus 32-41 mechanistic target of rapamycin kinase Homo sapiens 215-219 22872575-1 2012 PURPOSE: Sirolimus is the eponymous inhibitor of the mTOR; however, only its analogs have been approved as cancer therapies. Sirolimus 9-18 mechanistic target of rapamycin kinase Homo sapiens 53-57 22447639-12 2012 No obvious changes observed in the expression of AKT indicated that there might be a feedback loop effect by the mTOR inhibition induced by rapamycin. Sirolimus 140-149 mechanistic target of rapamycin kinase Homo sapiens 113-117 22861825-2 2012 Temsirolimus is an inhibitor of mTOR, and is a unique ester derivative of sirolimus, a macrocyclic lactone, with improved pharmaceutical properties, including stability and solubility. Sirolimus 3-12 mechanistic target of rapamycin kinase Homo sapiens 32-36 22527536-4 2012 The role of sirolimus, an mTOR inhibitor with immunomodulatory and anti-proliferative properties, has been less well-defined. Sirolimus 12-21 mechanistic target of rapamycin kinase Homo sapiens 26-30 22895726-3 2012 In addition, rapamycin, a clinically important immunosuppressant, is a specific and potent inhibitor of mTOR signaling. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 104-108 22895726-5 2012 We therefore performed an electrophysiological and morphological comparison of glutamatergic and GABAergic neurons in which mTOR signaling was either increased by loss of the repressor Pten or decreased by treatment with rapamycin. Sirolimus 221-230 mechanistic target of rapamycin kinase Homo sapiens 124-128 26894018-5 2012 mTOR inhibition with sirolimus or everolimus decreases cysts in most animal models of PKD including Pkd1 and Pkd2 gene deficient orthologous models of human disease. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 0-4 22710790-2 2012 Rapamycin, a specific inhibitor of mTOR, results predominately in G1 cell cycle arrest through translation control and occasionally, cell type-dependent apoptosis by an unknown mechanism. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 47-51 22447639-11 2012 Rapamycin could inhibit the proliferation and induce the apoptosis of human thyroid cancer cells in vitro by mTOR inhibition. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 109-113 22544534-6 2012 Clinical studies of rapamycin in human epilepsy are limited, but suggest that mTOR inhibitors at least have antiseizure effects in tuberous sclerosis patients. Sirolimus 20-29 mechanistic target of rapamycin kinase Homo sapiens 78-82 22329629-4 2012 The mTOR inhibitor rapamycin was found to restore both mitophagy and mitochondrial function in these cells. Sirolimus 19-28 mechanistic target of rapamycin kinase Homo sapiens 4-8 22117756-6 2012 We evaluated the effect of the mTOR inhibitor rapamycin, which has been previously shown to block hypoxia-inducible factor (HIF) 1alpha. Sirolimus 46-55 mechanistic target of rapamycin kinase Homo sapiens 31-35 21631587-1 2012 The mTOR inhibitors (ImTORs) sirolimus (SRL) and everolimus (EVR) have been increasingly used in renal transplantation as part of calcineurin inhibitor (CNI) sparing or avoidance regimens. Sirolimus 29-38 mechanistic target of rapamycin kinase Homo sapiens 4-8 22117756-15 2012 The hypoxic response is mediated partly through HIF1alpha and the mTOR inhibitor rapamycin blocks the hypoxic-induced angiogenic effects but does not affect the direct TGFbeta-mediated fibrosis and angiogenesis. Sirolimus 81-90 mechanistic target of rapamycin kinase Homo sapiens 66-70 22522471-5 2012 Treatment with rapamycin, a potent mTOR (mammalian target of rapamycin pathway)-pathway inhibitor, markedly diminished aggressive behavior. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 35-39 22261591-11 2012 PKI-587 is a potent inhibitor of AKT (Ser473), mTOR (Ser2448), and S6K (Thr389) phosphorylation; in contrast, rapamycin stimulated mTOR complex 2 substrate AKT(Ser473) phosphorylation although it inhibited mTOR complex 1 substrate S6K phosphorylation. Sirolimus 110-119 mechanistic target of rapamycin kinase Homo sapiens 131-135 22261591-11 2012 PKI-587 is a potent inhibitor of AKT (Ser473), mTOR (Ser2448), and S6K (Thr389) phosphorylation; in contrast, rapamycin stimulated mTOR complex 2 substrate AKT(Ser473) phosphorylation although it inhibited mTOR complex 1 substrate S6K phosphorylation. Sirolimus 110-119 mechanistic target of rapamycin kinase Homo sapiens 131-135 22696643-8 2012 Giant cells are associated with constitutive mammalian target of rapamycin (mTOR) activation, and we found that both giant LECs and LEC permeability were sensitive to rapamycin, an mTOR inhibitor, and VEGF-C addition. Sirolimus 65-74 mechanistic target of rapamycin kinase Homo sapiens 76-80 22522471-5 2012 Treatment with rapamycin, a potent mTOR (mammalian target of rapamycin pathway)-pathway inhibitor, markedly diminished aggressive behavior. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 41-70 22578218-7 2012 In the multiple-hit model of infantile spasms, pulse high-dose rapamycin administration can reduce the cortical overactivation of the mTOR pathway, suppresses spasms, and has disease-modifying effects by partially improving cognitive deficits. Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 134-138 24358826-1 2012 The recent development of mammalian target of rapamycin (mTOR) kinase domain inhibitors and genetic dissection of rapamycin-sensitive and -insensitive mTOR protein complexes (mTORC1 and mTORC2) have revealed that phosphorylation of the mTOR substrate 4E-BP1 on amino acids Thr37 and/or Thr46 represents a rapamycin-insensitive activity of mTORC1. Sirolimus 46-55 mechanistic target of rapamycin kinase Homo sapiens 57-61 22496407-4 2012 The activity of mTOR complex 1 (mTORC1) is necessary for renal regeneration and repair after AKI, and inhibition of mTORC1 by rapamycin has been shown to delay recovery from ischemic AKI in animal studies, and to prolong delayed graft function in humans who have received a kidney transplant. Sirolimus 126-135 mechanistic target of rapamycin kinase Homo sapiens 16-20 22645144-3 2012 We found that leucine-induced insulin secretion was inhibited by both the mTOR inhibitor rapamycin as well as the adrenergic alpha2 receptor agonist clonidine. Sirolimus 89-98 mechanistic target of rapamycin kinase Homo sapiens 74-78 22645144-7 2012 The role of the mTOR pathway in metabolic homeostasis led us to a second important finding in this study; retrospective analysis of clinical data showed that co-administration of rapamycin and clonidine was associated with an increased incidence of new-onset diabetes in renal transplantation patients over those receiving rapamycin alone. Sirolimus 179-188 mechanistic target of rapamycin kinase Homo sapiens 16-20 22645144-7 2012 The role of the mTOR pathway in metabolic homeostasis led us to a second important finding in this study; retrospective analysis of clinical data showed that co-administration of rapamycin and clonidine was associated with an increased incidence of new-onset diabetes in renal transplantation patients over those receiving rapamycin alone. Sirolimus 323-332 mechanistic target of rapamycin kinase Homo sapiens 16-20 22698676-10 2012 Since stromal loss of Cav-1 is a marker of a lethal tumor microenvironment in breast tumors, these high-risk patients might benefit from treatment with mTOR inhibitors, such as rapamycin or other rapamycin-related compounds (rapalogues). Sirolimus 177-186 mechanistic target of rapamycin kinase Homo sapiens 152-156 22698676-10 2012 Since stromal loss of Cav-1 is a marker of a lethal tumor microenvironment in breast tumors, these high-risk patients might benefit from treatment with mTOR inhibitors, such as rapamycin or other rapamycin-related compounds (rapalogues). Sirolimus 196-205 mechanistic target of rapamycin kinase Homo sapiens 152-156 23018254-1 2012 BACKGROUND: Calcineurin inhibitor (cyclosporine, CsA) and mTOR inhibitors (sirolimus, SRL) - immunosuppressants used to prevent allograft rejection after renal transplantation - have a narrow therapeutic index and show considerable inter-individual pharmacokinetic differences. Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 58-62 22751858-1 2012 Iatrogenic Kaposi sarcomas (KS) in organ transplant recipients are often treated by switching immunosuppressive therapy to an mTOR inhibitor, such as sirolimus or everolimus, as these have immunosuppressive as well as anti-tumor effects. Sirolimus 150-159 mechanistic target of rapamycin kinase Homo sapiens 126-130 21940156-4 2012 The incidence of BK-related events may be reduced in patients receiving mTOR inhibitors (everolimus or sirolimus) with cyclosporine vs a calcineurin inhibitor with mycophenolic acid. Sirolimus 103-112 mechanistic target of rapamycin kinase Homo sapiens 72-76 22552366-3 2012 In search of effective combination therapies, we show here that simultaneous targeting of EGFR with its inhibitor, erlotinib and mTOR with its inhibitor, rapamycin inhibits the phosphorylation and activation of downstream phosphatidylinositol 3-kinase (PI3K), Akt, mTOR and extracellular-signal-regulated kinase 1/2 (Erk1/2) pathways, resulting in the inhibition of cell cycle progression and the growth of both KRAS wild-type and mutated colorectal carcinoma cells. Sirolimus 178-187 mechanistic target of rapamycin kinase Homo sapiens 153-157 22552366-3 2012 In search of effective combination therapies, we show here that simultaneous targeting of EGFR with its inhibitor, erlotinib and mTOR with its inhibitor, rapamycin inhibits the phosphorylation and activation of downstream phosphatidylinositol 3-kinase (PI3K), Akt, mTOR and extracellular-signal-regulated kinase 1/2 (Erk1/2) pathways, resulting in the inhibition of cell cycle progression and the growth of both KRAS wild-type and mutated colorectal carcinoma cells. Sirolimus 178-187 mechanistic target of rapamycin kinase Homo sapiens 301-305 22344941-4 2012 Inhibition of mTOR by rapamycin improves cognitive deficits and rescues Abeta pathology and NFTs by increasing autophagy. Sirolimus 22-31 mechanistic target of rapamycin kinase Homo sapiens 14-18 22544507-6 2012 Specific inhibitors of mTOR are in clinical use, including sirolimus, everolimus, temsirolimus, and deforolimus. Sirolimus 59-68 mechanistic target of rapamycin kinase Homo sapiens 23-27 22488882-6 2012 This striking myelin pathology, with features of human CMT type 4B1 and HNPP, is dependent on AKT/mTOR signalling, as evidenced by a significant amelioration of the pathology in mice treated with rapamycin. Sirolimus 196-205 mechanistic target of rapamycin kinase Homo sapiens 98-102 22788941-4 2012 At present, inhibitors of mammalian target of rapamycin such as sirolimus appear to be the most promising therapeutic agents, although drug toxicity and development of resistance are potential problems. Sirolimus 64-73 mechanistic target of rapamycin kinase Homo sapiens 26-55 22428559-4 2012 Rapamycin inhibits some mTORC1 functions, whereas mTOR-KIs (mTOR kinase inhibitors) interfere with all of them. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 24-28 22758368-1 2012 Treatment with rapamycin, an inhibitor of mammalian target of rapamycin complex 1 (mTORC1) can increase mammalian life span. Sirolimus 15-24 mechanistic target of rapamycin kinase Homo sapiens 42-71 22758368-2 2012 However, extended treatment with rapamycin results in increased hepatic gluconeogenesis concomitant with glucose and insulin insensitivity through inhibition of mTOR complex 2 (C2). Sirolimus 33-42 mechanistic target of rapamycin kinase Homo sapiens 161-165 22420007-2 2012 The aim of this study was to evaluate the effects of the mTOR inhibitors sirolimus and temsirolimus on human ACC cell growth and cortisol production. Sirolimus 73-82 mechanistic target of rapamycin kinase Homo sapiens 57-61 22483750-9 2012 Coexpression of mTOR significantly increased I(glu), an effect reversed by rapamycin (100 nM). Sirolimus 75-84 mechanistic target of rapamycin kinase Homo sapiens 16-20 22333157-0 2012 mTOR inhibition with rapamycin causes impaired insulin signalling and glucose uptake in human subcutaneous and omental adipocytes. Sirolimus 21-30 mechanistic target of rapamycin kinase Homo sapiens 0-4 22466652-5 2012 Mouse models of obesity also exhibit increased hepatic activity of mammalian target of rapamycin complex 1 (mTORC1) and ER stress, and we found that administration of the mTOR inhibitor rapamycin to ob/ob mice reduced ER stress and increased hepatic sortilin-1 levels. Sirolimus 87-96 mechanistic target of rapamycin kinase Homo sapiens 108-112 22338016-4 2012 EXPERIMENTAL DESIGN: We sought to identify a GEP of mTOR inhibitor resistance by stratification of eight DLBCL cell lines with respect to response to rapamycin. Sirolimus 150-159 mechanistic target of rapamycin kinase Homo sapiens 52-56 22343118-0 2012 Dose-dependent effects of sirolimus on mTOR signaling and polycystic kidney disease. Sirolimus 26-35 mechanistic target of rapamycin kinase Homo sapiens 39-43 22577264-10 2012 Furthermore, rapamycin and wortmannin, inhibitors of mTOR and PI3K, respectively, have co-stimulatory effects with alpha-MSH in enhancing melanogenesis in melanocyte cells. Sirolimus 13-22 mechanistic target of rapamycin kinase Homo sapiens 53-57 22409888-8 2012 The preclinical efficacy of mTOR inhibition by rapamycin and RAD001 was explored in HPV(+) HNSCC and CCSCC tumor xenografts. Sirolimus 47-56 mechanistic target of rapamycin kinase Homo sapiens 28-32 22449574-4 2012 Here we demonstrate that besides inhibiting their respective target kinases, the pharmacological PI3-kinase inhibitor LY294002 and the downstream mTOR kinase inhibitor rapamycin also directly inhibit ABCG2 function. Sirolimus 168-177 mechanistic target of rapamycin kinase Homo sapiens 146-150 22450807-5 2012 We therefore hypothesized that the mTOR inhibitor rapamycin would increase LPS-induced apoptosis and lung injury in vivo. Sirolimus 50-59 mechanistic target of rapamycin kinase Homo sapiens 35-39 22399302-4 2012 By fluorescence confocal microscopy, inactivation of mTOR with rapamycin promoted the nuclear translocation of unphosphorylated STAT1, but not that of a STAT1 mutant incapable of binding its nuclear import adaptor karyopherin-alpha1 (KPNA1). Sirolimus 63-72 mechanistic target of rapamycin kinase Homo sapiens 53-57 22399302-5 2012 By immunoprecipitation, KPNA1 was physically associated with mTOR and STAT1 in a complex that translocated to the nucleus in response to rapamycin. Sirolimus 137-146 mechanistic target of rapamycin kinase Homo sapiens 61-65 22520346-7 2012 Increased understanding of the genetic cause of the disease and underlying dysregulation of the mammalian target of rapamycin pathway has led to clinical trials of mammalian target of rapamycin inhibitors, including sirolimus and everolimus. Sirolimus 216-225 mechanistic target of rapamycin kinase Homo sapiens 96-125 22520346-7 2012 Increased understanding of the genetic cause of the disease and underlying dysregulation of the mammalian target of rapamycin pathway has led to clinical trials of mammalian target of rapamycin inhibitors, including sirolimus and everolimus. Sirolimus 216-225 mechanistic target of rapamycin kinase Homo sapiens 164-193 22311674-2 2012 mTOR inhibitors, including rapamycin (sirolimus), are currently being evaluated in cancer trials. Sirolimus 27-36 mechanistic target of rapamycin kinase Homo sapiens 0-4 22287562-7 2012 Inhibition of the AKT-mTOR pathway with rapamycin significantly reduced the size of high-grade papillary UCB but hyperactivated mitogen-activated protein kinase (MAPK). Sirolimus 40-49 mechanistic target of rapamycin kinase Homo sapiens 22-26 22275355-6 2012 Although mycobacterial infection potently induces mTOR activity, we confirm that bacterial viability can be reduced by rapamycin treatment. Sirolimus 119-128 mechanistic target of rapamycin kinase Homo sapiens 50-54 22014210-2 2012 However, new-onset diabetes is a frequent complication occurring in patients treated with mTOR inhibitors such as rapamycin (Sirolimus). Sirolimus 114-123 mechanistic target of rapamycin kinase Homo sapiens 90-94 22014210-2 2012 However, new-onset diabetes is a frequent complication occurring in patients treated with mTOR inhibitors such as rapamycin (Sirolimus). Sirolimus 125-134 mechanistic target of rapamycin kinase Homo sapiens 90-94 22311674-2 2012 mTOR inhibitors, including rapamycin (sirolimus), are currently being evaluated in cancer trials. Sirolimus 38-47 mechanistic target of rapamycin kinase Homo sapiens 0-4 21618507-10 2012 We also found that treatment of cells with mTOR inhibitor rapamycin and mTOR-siRNA caused decrease in phosphorylation of mTOR and its target proteins which were further downregulated on treatment with fisetin, suggesting that these effects are mediated in part, through mTOR signaling. Sirolimus 58-67 mechanistic target of rapamycin kinase Homo sapiens 43-47 21701901-11 2012 Sirolimus, a specific inhibitor of mTOR pathway, inhibited MHV68-induced hepatic expression of serine p-IRS-1, increased total IRS-1 levels and improved MHV68-induced hepatic insulin resistance. Sirolimus 0-9 mechanistic target of rapamycin kinase Homo sapiens 35-39 22246168-8 2012 The PI3K/AKT inhibitor, LY294002, and the mTOR inhibitor, rapamycin, largely neutralized the protective effects of niacin, suggesting that AKT and downstream signaling mTOR/S6 activation are necessary for the niacin-induced protective effects against UV-induced cell death and cell apoptosis. Sirolimus 70-79 mechanistic target of rapamycin kinase Homo sapiens 54-58