PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 16740780-8 2006 Addition of imatinib to ADW742 synergistically augmented these effects and was especially effective in inhibiting AKT/mTOR phosphorylation and reducing vascular endothelial growth factor expression in cell lines having high IGF1R activation levels. Imatinib Mesylate 12-20 mechanistic target of rapamycin kinase Homo sapiens 118-122 18223253-2 2008 We have previously shown that the mTOR/p70 S6 kinase (p70 S6K) pathway is constitutively activated in BCR-ABL transformed cells and that inhibition of BCR-ABL kinase activity by imatinib mesylate abrogates such activation. Imatinib Mesylate 178-195 mechanistic target of rapamycin kinase Homo sapiens 34-38 16908864-4 2006 Analysis of tumor tissue from imatinib-treated mice showed diminished phosphatidylinositol 3-kinase (PI3-kinase) and mammalian target of rapamycin (mTOR) signaling suggesting that oncogenic Kit signaling critically contributes to the translational response in GIST. Imatinib Mesylate 30-38 mechanistic target of rapamycin kinase Homo sapiens 117-146 16908864-4 2006 Analysis of tumor tissue from imatinib-treated mice showed diminished phosphatidylinositol 3-kinase (PI3-kinase) and mammalian target of rapamycin (mTOR) signaling suggesting that oncogenic Kit signaling critically contributes to the translational response in GIST. Imatinib Mesylate 30-38 mechanistic target of rapamycin kinase Homo sapiens 148-152 28777148-3 2019 Recently, activation of mTOR pathway independent of KIT signaling was demonstrated in imatinib mesylate naive malignant GISTs and treatment-resistant metastatic tumors. Imatinib Mesylate 86-103 mechanistic target of rapamycin kinase Homo sapiens 24-28 15790787-6 2005 In contrast to the effects of IFNs, imatinib mesylate suppressed p70 S6 kinase activity, consistent with inhibition of BCR-ABL-mediated activation of the mTOR/p70 S6 kinase pathway. Imatinib Mesylate 36-53 mechanistic target of rapamycin kinase Homo sapiens 154-158 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). Imatinib Mesylate 75-92 mechanistic target of rapamycin kinase Homo sapiens 14-18 15790787-8 2005 Taken altogether, our data demonstrate that IFNs and imatinib mesylate differentially regulate PI 3" kinase/mTOR-dependent signaling cascades in BCR-ABL-transformed cells, consistent with distinct effects of these agents on pathways regulating mRNA translation. Imatinib Mesylate 53-70 mechanistic target of rapamycin kinase Homo sapiens 108-112 35313299-0 2022 MiR-199a-3p Overexpression Suppressed Cell Proliferation and Sensitized Chronic Myeloid Leukaemia Cells to Imatinib by Inhibiting mTOR Signalling. Imatinib Mesylate 107-115 mechanistic target of rapamycin kinase Homo sapiens 130-134 35313299-11 2022 Both miR-199a-3p overexpression and mTOR silencing inhibited CML cell proliferation, promoted CML cell apoptosis and sensitized these cells to imatinib. Imatinib Mesylate 143-151 mechanistic target of rapamycin kinase Homo sapiens 36-40 35313299-12 2022 mTOR silencing reversed the promoting effect of miR-199a-3p inhibition on the proliferation of CML cells and the inhibitory effects on cell apoptosis and sensitivity to imatinib. Imatinib Mesylate 169-177 mechanistic target of rapamycin kinase Homo sapiens 0-4 35313299-14 2022 CONCLUSION: MiR-199a-3p suppressed cell propagation, facilitated apoptosis of CML cells and sensitized CML cells to imatinib by downregulating mTOR signalling. Imatinib Mesylate 116-124 mechanistic target of rapamycin kinase Homo sapiens 143-147 16136169-0 2005 Compensatory PI3-kinase/Akt/mTor activation regulates imatinib resistance development. Imatinib Mesylate 54-62 mechanistic target of rapamycin kinase Homo sapiens 28-32 14522890-6 2003 The mTOR inhibitor rapamycin enhanced imatinib-mediated killing of CML cell lines in vitro, and it overcame imatinib resistance in cells with Bcr-Abl gene amplification. Imatinib Mesylate 38-46 mechanistic target of rapamycin kinase Homo sapiens 4-8 14522890-6 2003 The mTOR inhibitor rapamycin enhanced imatinib-mediated killing of CML cell lines in vitro, and it overcame imatinib resistance in cells with Bcr-Abl gene amplification. Imatinib Mesylate 108-116 mechanistic target of rapamycin kinase Homo sapiens 4-8 34893099-7 2021 CONCLUSION: CML imatinib resistance is associated with oxidative phosphorylation, during which the pathway of TGF-beta and mTOR are significantly up-regulated. Imatinib Mesylate 16-24 mechanistic target of rapamycin kinase Homo sapiens 123-127 35597499-12 2022 Immunofluorescence experiments and western blot results showed that psoralen could affect ROS levels and downstream Nrf2 and mTOR protein changes, whereas the ABL1 inhibitor imatinib and ABL1 agonist DPH could enhance or inhibit this effect. Imatinib Mesylate 174-182 mechanistic target of rapamycin kinase Homo sapiens 125-129 33603171-7 2021 Given that CAF paracrine signaling modulated GIST biology, we directly targeted CAFs with a dual PI3K/mTOR inhibitor, which synergized with imatinib to increase tumor cell killing and in vivo disease response. Imatinib Mesylate 140-148 mechanistic target of rapamycin kinase Homo sapiens 102-106 33022360-7 2020 Also, Imatinib could independently deregulate the other cell survival and proliferation signaling e.g. PI3-K/Akt/mTOR, Wnt/beta-catenin and MAPK. Imatinib Mesylate 6-14 mechanistic target of rapamycin kinase Homo sapiens 113-117 28777148-5 2019 In this study, mTOR pathway genes were evaluated in 14 imatinib mesylate naive, KIT-mutant, malignant small intestinal GISTs using next-generation sequencing. Imatinib Mesylate 55-63 mechanistic target of rapamycin kinase Homo sapiens 15-19 26617858-9 2015 As compared with the control (GIST-R cells without any treatment), the expression levels of p-mTOR and Bcl-2 proteins of GIST-R cells in combination of Peg-IFNalpha-2b and imatinib group were decreased (P<0.01). Imatinib Mesylate 172-180 mechanistic target of rapamycin kinase Homo sapiens 94-98 29552859-8 2018 The results indicated that PD increased the sensitivity of drug-resistant cells to imatinib, and the inhibitory effect of PD combined with imatinib was significantly better than the single drug on cell proliferation, induction of apoptosis, inhibition of Bcr/abl protein and PI3K/AKT/mTOR signaling pathway. Imatinib Mesylate 139-147 mechanistic target of rapamycin kinase Homo sapiens 284-288 29423045-8 2018 Additionally, Ova alone or in combination with Imatinib suppressed the hCSC traits of the CD34+/CD38- cells, resulting in loss of their ability to form tumorspheres, enhanced apoptosis, increase in the Bax/Bcl-2 ratio, and dysregulation of the PI3K/AKT/mTOR signaling pathway. Imatinib Mesylate 47-55 mechanistic target of rapamycin kinase Homo sapiens 253-257 29046392-5 2017 Here, we reported that nutlin-3 plus tanshinone IIA significantly potentiated the cytotoxic and apoptotic induction effects of imatinib by downregulation of the AKT/mTOR pathway and reactivating p53 pathway deeply in Ph+ acute lymphoblastic leukemia cell line. Imatinib Mesylate 127-135 mechanistic target of rapamycin kinase Homo sapiens 165-169 28962554-9 2017 Interestingly, the levels of p-Akt, p-mTOR and p-S6 are lower in cells treated with combination of propofol and imatinib than cells treated with propofol or imatinib alone, suggesting that propofol augments BCR-ABL TKI"s inhibitory effect via suppressing Akt/mTOR pathway. Imatinib Mesylate 112-120 mechanistic target of rapamycin kinase Homo sapiens 38-42 28962554-9 2017 Interestingly, the levels of p-Akt, p-mTOR and p-S6 are lower in cells treated with combination of propofol and imatinib than cells treated with propofol or imatinib alone, suggesting that propofol augments BCR-ABL TKI"s inhibitory effect via suppressing Akt/mTOR pathway. Imatinib Mesylate 112-120 mechanistic target of rapamycin kinase Homo sapiens 259-263 28711648-11 2017 The Akt-mTOR pathway is thus a potential therapeutic target in imatinib-resistant DFSP/FS. Imatinib Mesylate 63-71 mechanistic target of rapamycin kinase Homo sapiens 8-12 28442505-8 2017 Compared with both monotherapies, the C75/imatinib combination more effectively suppressed the growth of xenografts, exhibiting decreased KIT phosphorylation, Ki-67, and phosphorylated PI3K/AKT/mTOR levels and increased TUNEL labeling.Conclusions: We have characterized the prognostic, biological, and therapeutic implications of overexpressed FASN in GISTs. Imatinib Mesylate 42-50 mechanistic target of rapamycin kinase Homo sapiens 194-198 26892093-0 2016 Hsp90 inhibitor, BIIB021, induces apoptosis and autophagy by regulating mTOR-Ulk1 pathway in imatinib-sensitive and -resistant chronic myeloid leukemia cells. Imatinib Mesylate 93-101 mechanistic target of rapamycin kinase Homo sapiens 72-76 26898422-0 2016 Heme oxygenase-1 contributes to imatinib resistance by promoting autophagy in chronic myeloid leukemia through disrupting the mTOR signaling pathway. Imatinib Mesylate 32-40 mechanistic target of rapamycin kinase Homo sapiens 126-130 28612529-6 2017 CONCLUSION: The combination of IM and PP242 could increase the inhibition of PI3K/Akt/mTOR signaling pathway and apoptosis mediated by bax and caspase-3 in SUP-B15 cell line. Imatinib Mesylate 31-33 mechanistic target of rapamycin kinase Homo sapiens 86-90 26919095-4 2016 In imatinib-resistant CML cells, high concentration of imatinib is required to strongly inhibit Bcr-Abl, ERK1/2 and Akt Ser473 phosphorylation, but under these conditions the phosphorylation of rpS6, a common downstream effector of MEK/ERK1/2 and PI3K/Akt/mTOR pathways is only slightly reduced. Imatinib Mesylate 55-63 mechanistic target of rapamycin kinase Homo sapiens 256-260 25979368-7 2015 Curcumin exerted synergetic anti-leukemia effects with imatinib by inhibition of the imatinib-mediated overactivation of AKT/mTOR signaling and down-regulation of BCR/ABL gene expression. Imatinib Mesylate 85-93 mechanistic target of rapamycin kinase Homo sapiens 125-129 25979368-0 2015 Curcumin potentiates the anti-leukemia effects of imatinib by downregulation of the AKT/mTOR pathway and BCR/ABL gene expression in Ph+ acute lymphoblastic leukemia. Imatinib Mesylate 50-58 mechanistic target of rapamycin kinase Homo sapiens 88-92 22895079-9 2012 Oridonin plus imatinib exerted synergetic effects by overcoming imatinib defect of upregulating Akt/mTOR and LYN signaling. Imatinib Mesylate 14-22 mechanistic target of rapamycin kinase Homo sapiens 100-104 25979368-7 2015 Curcumin exerted synergetic anti-leukemia effects with imatinib by inhibition of the imatinib-mediated overactivation of AKT/mTOR signaling and down-regulation of BCR/ABL gene expression. Imatinib Mesylate 55-63 mechanistic target of rapamycin kinase Homo sapiens 125-129 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. Imatinib Mesylate 42-50 mechanistic target of rapamycin kinase Homo sapiens 91-95 24260131-4 2013 Catalytic mTOR inhibition also results in upregulation of SESN3 expression in cells harboring the TKI-insensitive T315I-BCR-ABL mutant, which is resistant to imatinib mesylate. Imatinib Mesylate 158-175 mechanistic target of rapamycin kinase Homo sapiens 10-14 25757539-0 2015 PI3K/AKT/mTOR pathway is activated after imatinib secondary resistance in gastrointestinal stromal tumors (GISTs). Imatinib Mesylate 41-49 mechanistic target of rapamycin kinase Homo sapiens 9-13 25757539-1 2015 Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of the rapamycin (mTOR) pathway activation may be related to imatinib resistance; however, no study has focused on whether signal conduction of this pathway will change after imatinib resistance. Imatinib Mesylate 119-127 mechanistic target of rapamycin kinase Homo sapiens 76-80 25757539-1 2015 Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of the rapamycin (mTOR) pathway activation may be related to imatinib resistance; however, no study has focused on whether signal conduction of this pathway will change after imatinib resistance. Imatinib Mesylate 233-241 mechanistic target of rapamycin kinase Homo sapiens 76-80 25757539-4 2015 The activation of AKT/mTOR was significantly higher in imatinib secondary resistant GIST (53.1 %) than in imatinib-sensitive (27.1 %) and primary resistant GIST (33.3 %) (P = 0.049). Imatinib Mesylate 55-63 mechanistic target of rapamycin kinase Homo sapiens 22-26 25757539-4 2015 The activation of AKT/mTOR was significantly higher in imatinib secondary resistant GIST (53.1 %) than in imatinib-sensitive (27.1 %) and primary resistant GIST (33.3 %) (P = 0.049). Imatinib Mesylate 106-114 mechanistic target of rapamycin kinase Homo sapiens 22-26 25757539-6 2015 AKT/mTOR status was inactivated in pre-imatinib and on-treatment samples in eight patients with effective imatinib; however, the status of six patients was changed from inactivated to activated in 12 patients at the time of tumor progression. Imatinib Mesylate 39-47 mechanistic target of rapamycin kinase Homo sapiens 4-8 25757539-6 2015 AKT/mTOR status was inactivated in pre-imatinib and on-treatment samples in eight patients with effective imatinib; however, the status of six patients was changed from inactivated to activated in 12 patients at the time of tumor progression. Imatinib Mesylate 106-114 mechanistic target of rapamycin kinase Homo sapiens 4-8 25757539-8 2015 PI3K/AKT/mTOR pathway can be partly activated after imatinib secondary resistance in GIST. Imatinib Mesylate 52-60 mechanistic target of rapamycin kinase Homo sapiens 9-13 25375091-0 2014 MTOR inhibition enhances NVP-AUY922-induced autophagy-mediated KIT degradation and cytotoxicity in imatinib-resistant gastrointestinal stromal tumors. Imatinib Mesylate 99-107 mechanistic target of rapamycin kinase Homo sapiens 0-4 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. Imatinib Mesylate 147-155 mechanistic target of rapamycin kinase Homo sapiens 31-35 24112092-0 2014 Mammalian target of rapamycin inhibitor rapamycin enhances anti-leukemia effect of imatinib on Ph+ acute lymphoblastic leukemia cells. Imatinib Mesylate 83-91 mechanistic target of rapamycin kinase Homo sapiens 0-29 23395818-3 2013 Inhibition of the mammalian target of rapamycin (mTOR) in imatinib-resistant BCR-ABL1-positive cells was effective in vitro, but in a pilot clinical trial, only a few patients responded to the treatment. Imatinib Mesylate 58-66 mechanistic target of rapamycin kinase Homo sapiens 18-47 23395818-3 2013 Inhibition of the mammalian target of rapamycin (mTOR) in imatinib-resistant BCR-ABL1-positive cells was effective in vitro, but in a pilot clinical trial, only a few patients responded to the treatment. Imatinib Mesylate 58-66 mechanistic target of rapamycin kinase Homo sapiens 49-53 22895079-0 2012 Oridonin in combination with imatinib exerts synergetic anti-leukemia effect in Ph+ acute lymphoblastic leukemia cells in vitro by inhibiting activation of LYN/mTOR signaling pathway. Imatinib Mesylate 29-37 mechanistic target of rapamycin kinase Homo sapiens 160-164 22895079-9 2012 Oridonin plus imatinib exerted synergetic effects by overcoming imatinib defect of upregulating Akt/mTOR and LYN signaling. Imatinib Mesylate 64-72 mechanistic target of rapamycin kinase Homo sapiens 100-104 22895079-11 2012 Our data showed that oridonin remarkably suppressed activations of Akt/mTOR, Raf/MEK and STAT5 pathway in these primary specimens and oridonin with imatinib exerted synergetic suppressive effects on mTOR, STAT5 and LYN signaling in one imatinib resistant patient specimen. Imatinib Mesylate 148-156 mechanistic target of rapamycin kinase Homo sapiens 199-203 21993902-3 2012 Recent studies showed that mTOR pathway can increase responses to imatinib. Imatinib Mesylate 78-86 mechanistic target of rapamycin kinase Homo sapiens 39-43 21392556-10 2011 CONCLUSIONS: These results demonstrate that SphK1 is upregulated in imatinib-resistant K562 cells by a pathway contingent on a phosphoinositide 3-kinase/AKT2/mammalian target of rapamycin signaling pathway. Imatinib Mesylate 68-76 mechanistic target of rapamycin kinase Homo sapiens 158-187 21715304-7 2011 We demonstrate that imatinib-induced autophagy is because of inhibition of the BCR-ABL/PI3K/AKT/FOXO4/ATF5/mTOR pathway that we have identified in this study. Imatinib Mesylate 20-28 mechanistic target of rapamycin kinase Homo sapiens 107-111 21392556-0 2011 Sphingosine kinase 1 overexpression is regulated by signaling through PI3K, AKT2, and mTOR in imatinib-resistant chronic myeloid leukemia cells. Imatinib Mesylate 94-102 mechanistic target of rapamycin kinase Homo sapiens 86-90 19643477-0 2010 mTOR inhibitor RAD001 (Everolimus) enhances the effects of imatinib in chronic myeloid leukemia by raising the nuclear expression of c-ABL protein. Imatinib Mesylate 59-67 mechanistic target of rapamycin kinase Homo sapiens 0-4 21299849-10 2011 PI3K pathway inhibitors effected dephosphorylation of RPS6 in imatinib-resistant cell lines suggesting that an oncogene other than BCR-ABL1 might be responsible for activation of the PI3K/AKT1/mTOR pathway, which would explain the TKI resistance of these cells. Imatinib Mesylate 62-70 mechanistic target of rapamycin kinase Homo sapiens 193-197 20499309-10 2010 The KIT secondary mutation and PI3-K/AKT/MTOR pathway are particularly relevant for therapeutic targeting in imatinib-resistant GIST. Imatinib Mesylate 109-117 mechanistic target of rapamycin kinase Homo sapiens 41-45 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. Imatinib Mesylate 251-259 mechanistic target of rapamycin kinase Homo sapiens 49-53 19846571-5 2010 Treatment with c-Abl or mTOR inhibitors, imatinib mesylate and rapamycin, respectively, each blocks noncanonical (non-smad) TGF-beta pathways in the kidney in vivo and diminishes the number of interstitial fibroblasts and myofibroblasts as well as the interstitial accumulation of extracellular matrix proteins. Imatinib Mesylate 41-58 mechanistic target of rapamycin kinase Homo sapiens 24-28 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. Imatinib Mesylate 251-259 mechanistic target of rapamycin kinase Homo sapiens 59-88