PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 32738450-13 2021 The mTOR inhibitor rapamycin significantly reduced hepatocarcinogenesis triggered by Tsc1 loss and p53 haploinsufficiency in vivo, as well as the biomarker Abcc4. Sirolimus 19-28 TSC complex subunit 1 Mus musculus 85-89 33352197-0 2021 Rapamycin ameliorates corneal injury after alkali burn through methylation modification in mouse TSC1 and mTOR genes. Sirolimus 0-9 TSC complex subunit 1 Mus musculus 97-101 32484794-4 2020 Injection of rapamycin to pregnant mice inhibited the mTOR pathway and tubular cell proliferation in kidneys of TSC1 null offspring. Sirolimus 13-22 TSC complex subunit 1 Mus musculus 112-116 33159078-1 2020 Lymphangioleiomyomatosis (LAM) is a rare fatal cystic lung disease due to bi-allelic inactivating mutations in tuberous sclerosis complex (TSC1/TSC2) genes coding for suppressors of the mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 208-217 TSC complex subunit 1 Mus musculus 139-143 32588887-2 2020 TSC results from inactivating variants within the TSC1 or TSC2 genes, leading to constitutive activation of mechanistic Target of Rapamycin Complex 1 (mTORC1) signaling. Sirolimus 130-139 TSC complex subunit 1 Mus musculus 0-3 32588887-2 2020 TSC results from inactivating variants within the TSC1 or TSC2 genes, leading to constitutive activation of mechanistic Target of Rapamycin Complex 1 (mTORC1) signaling. Sirolimus 130-139 TSC complex subunit 1 Mus musculus 50-54 32484794-6 2020 Gene expression analysis of proximal tubule cells, identified sets of genes and pathways that were modified secondary to TSC1 deletion and rescued by rapamycin administration during nephrogenesis. Sirolimus 150-159 TSC complex subunit 1 Mus musculus 121-125 32375878-2 2020 TSC1 and TSC2 are repressors of the mechanistic target of rapamycin complex 1 (mTORC1), a key regulator of protein synthesis. Sirolimus 58-67 TSC complex subunit 1 Mus musculus 0-4 31433805-3 2019 Here, we demonstrate a special metabolic-epigenetic coupling mechanism orchestrated by tuberous sclerosis complex subunit 1 (TSC1)-mechanistic target of rapamycin (mTOR) for homeostatic DC function. Sirolimus 153-162 TSC complex subunit 1 Mus musculus 87-123 31078684-6 2019 Loss of either Tsc1 or Tsc2 from astrocytes resulted in a marked increase in Aqp4 expression which was sensitive to mTORC1 inhibition with rapamycin. Sirolimus 139-148 TSC complex subunit 1 Mus musculus 15-19 31433805-3 2019 Here, we demonstrate a special metabolic-epigenetic coupling mechanism orchestrated by tuberous sclerosis complex subunit 1 (TSC1)-mechanistic target of rapamycin (mTOR) for homeostatic DC function. Sirolimus 153-162 TSC complex subunit 1 Mus musculus 125-129 30185506-6 2018 Rapamycin restored LPS-induced up-regulation of EDN1, endothelin converting enzyme-1 (ECE1), and p-JNK in TSC1-knockdown mouse embryonic fibroblasts (MEFs). Sirolimus 0-9 TSC complex subunit 1 Mus musculus 106-110 30816216-2 2019 Dysregulation of mTOR signaling has been implicated in the pathogenesis of certain types of ASD, and inhibition of mTOR by rapamycin has been demonstrated to be an effective therapeutics for impaired social interaction in Tsc1+/-, Tsc2+/-, Pten-/- mice and valproic acid-induced ASD animal models. Sirolimus 123-132 TSC complex subunit 1 Mus musculus 222-226 31353861-8 2019 Tsc1 gene deletion resulted in a strong activation of the mTORC1 pathway, and both epileptogenesis and lethality could be entirely prevented by RHEB1 gene deletion or rapamycin treatment. Sirolimus 167-176 TSC complex subunit 1 Mus musculus 0-4 30247156-8 2018 Treatment with rapamycin and the antioxidant N-acetylcysteine rescued Tsc1-cKO hair cells from injury in vivo. Sirolimus 15-24 TSC complex subunit 1 Mus musculus 70-74 28844017-0 2017 Assessment of Response of Kidney Tumors to Rapamycin and Atorvastatin in Tsc1+/- Mice. Sirolimus 43-52 TSC complex subunit 1 Mus musculus 73-77 30079598-5 2018 RESULTS: Tsc1Cx3cr1-Cre CKO mice exhibited a high efficiency of microglia Tsc1 inactivation, mTORC1 activation, increased microglial size and number, and robust epilepsy, which were rapamycin-dependent. Sirolimus 182-191 TSC complex subunit 1 Mus musculus 9-13 28701517-5 2017 Furthermore, rapamycin treatment of Foxd1ER(+) TSC1 mice suppressed mesangial expansion. Sirolimus 13-22 TSC complex subunit 1 Mus musculus 47-51 29396625-7 2018 The elongated cilium phenotype of Tsc1-/- MEFs is likely due to increased mTORC1-dependent autophagic flux observed in these cells, as both the autophagic flux and the cilia length phenotype was restored by rapamycin. Sirolimus 207-216 TSC complex subunit 1 Mus musculus 34-38 29635516-1 2018 Tuberous sclerosis complex (TSC) is an autosomal dominant neurodevelopmental disorder and the quintessential disorder of mechanistic Target of Rapamycin Complex 1 (mTORC1) dysregulation. Sirolimus 143-152 TSC complex subunit 1 Mus musculus 28-31 28972182-7 2017 However, rapamycin further increased uPA expression in TSC2-null tumor cells and immortalized TSC2-null angiomyolipoma cells, but not in cells with intact TSC. Sirolimus 9-18 TSC complex subunit 1 Mus musculus 55-58 28775826-0 2017 A brain proteomic investigation of rapamycin effects in the Tsc1+/- mouse model. Sirolimus 35-44 TSC complex subunit 1 Mus musculus 60-64 28520214-5 2017 Conversely, BMMs lacking Tsc1 exhibited a severe defect in osteoclast-like differentiation and absorptive function, both of which were restored following rapamycin treatment. Sirolimus 154-163 TSC complex subunit 1 Mus musculus 25-29 28808237-1 2017 Tuberous Sclerosis Complex (TSC) is a rare genetic disorder that results from a mutation in the TSC1 or TSC2 genes leading to constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 179-188 TSC complex subunit 1 Mus musculus 96-100 28775826-3 2017 Heterozygocity induces hyperactivation of mTOR which can be inhibited by mTOR inhibitors, such as rapamycin, which have proven efficacy in the treatment of TSC-associated symptoms. Sirolimus 98-107 TSC complex subunit 1 Mus musculus 156-159 28775826-4 2017 The aim of the present study was (1) to identify molecular changes associated with social and cognitive deficits in the brain tissue of Tsc1+/- mice and (2) to investigate the molecular effects of rapamycin treatment, which has been shown to ameliorate genotype-related behavioural deficits. Sirolimus 197-206 TSC complex subunit 1 Mus musculus 136-140 28775826-13 2017 Rapamycin treatment exerted a stronger proteomic effect in Tsc1+/- mice with significant changes (mainly decreased expression) in 231 and 106 proteins, respectively. Sirolimus 0-9 TSC complex subunit 1 Mus musculus 59-63 28775826-14 2017 The cellular pathways "oxidative stress" and "apoptosis" were found to be affected in Tsc1+/- mice and the cellular compartments "myelin sheet" and "neurofilaments" were affected by rapamycin treatment. Sirolimus 182-191 TSC complex subunit 1 Mus musculus 86-90 28775826-15 2017 Thirty-three proteins which were altered in Tsc1+/- mice were normalized following rapamycin treatment, amongst them oxidative stress related proteins, myelin-specific and ribosomal proteins. Sirolimus 83-92 TSC complex subunit 1 Mus musculus 44-48 27362797-6 2016 Because cells with TSC loss fail to completely inhibit mTORC1 and properly activate autophagy in the absence of amino acids, we sporadically administered the mTORC1 inhibitor rapamycin, which was sufficient to correct the defects seen in cones, further enhancing the efficiency of cone survival mediated by Tsc1 loss. Sirolimus 175-184 TSC complex subunit 1 Mus musculus 307-311 27524416-4 2017 Pituitary knockout of either mTOR signaling pathway negative regulator Tsc1 or Pten caused mouse pituitary prolactinoma, which was abolished by rapamycin treatment. Sirolimus 144-153 TSC complex subunit 1 Mus musculus 71-75 26991739-6 2016 Treatment with 5 mg/kg rapamycin for 3 weeks to inhibit mTORC1 and mTORC2 fully reversed PH in SM22-TSC1(-/-) mice. Sirolimus 23-32 TSC complex subunit 1 Mus musculus 100-104 25613864-1 2015 The genetic disease tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by loss of function mutations in either TSC1 (hamartin) or TSC2 (tuberin), which serve as negative regulators of mechanistic target of rapamycin complex 1 (mTORC1) activity. Sirolimus 229-238 TSC complex subunit 1 Mus musculus 48-51 26296742-7 2016 Furthermore, pharmacologic treatment of Tsc1 single-mutant mice with rapamycin reduced hyperphosphorylation and accumulation of 4E-BP1 but also inhibited phosphorylation of rpS6. Sirolimus 69-78 TSC complex subunit 1 Mus musculus 40-44 26655465-1 2016 Expression of hypoxia-inducible factor 1a (HIF1a) is increased under several pathological conditions such as hyperactive mechanistic target of rapamycin complex 1 (mTORC1) in tuberous sclerosis complex (TSC). Sirolimus 143-152 TSC complex subunit 1 Mus musculus 203-206 26846849-9 2016 Following acute Tsc1 deletion from hepatocytes, Akt phosphorylation, but not IRS1/PI3K association, was rapidly restored by treatment with the mTORC1 inhibitor rapamycin. Sirolimus 160-169 TSC complex subunit 1 Mus musculus 16-20 26795955-3 2016 Phosphorylated S6 was up-regulated in Tsc1(-/-) mammary epithelium, which could be reversed by rapamycin, suggesting that mTORC1 was hyperactivated in Tsc1(-/-) mammary epithelium. Sirolimus 95-104 TSC complex subunit 1 Mus musculus 38-42 26795955-3 2016 Phosphorylated S6 was up-regulated in Tsc1(-/-) mammary epithelium, which could be reversed by rapamycin, suggesting that mTORC1 was hyperactivated in Tsc1(-/-) mammary epithelium. Sirolimus 95-104 TSC complex subunit 1 Mus musculus 151-155 26795955-4 2016 The mTORC1 inhibitor rapamycin restored the development of Tsc1(-/-) mammary glands whereas suppressed the development of Tsc1(wt/wt) mammary glands, indicating that a modest activation of mTORC1 is critical for mammary development. Sirolimus 21-30 TSC complex subunit 1 Mus musculus 59-63 26795955-4 2016 The mTORC1 inhibitor rapamycin restored the development of Tsc1(-/-) mammary glands whereas suppressed the development of Tsc1(wt/wt) mammary glands, indicating that a modest activation of mTORC1 is critical for mammary development. Sirolimus 21-30 TSC complex subunit 1 Mus musculus 122-126 26224859-6 2015 Importantly, transcripts for the activating transcription factor-3 (Atf3) and mitochondrial uncoupling protein-2 (Ucp2) are highly induced in Tsc2-deficient neurons, as well as in a neuron-specific Tsc1 conditional knock-out mouse model, and show differential responses to the mTOR inhibitor rapamycin. Sirolimus 292-301 TSC complex subunit 1 Mus musculus 198-202 26122303-6 2015 Based on the Western blot studies, different dosing paradigms of rapamycin starting at postnatal day 21 were tested for their ability to prevent epilepsy or pathologic abnormalities in Tsc1(GFAP)CKO mice: 4 days of rapamycin only (4- ), 4 days on-24 days off (4-24), and 4 days on-10 days off (4-10). Sirolimus 65-74 TSC complex subunit 1 Mus musculus 185-189 26122303-9 2015 SIGNIFICANCE: Intermittent dosing of rapamycin, with drug holidays of more than 3 weeks, maintains significant antiepileptogenic properties in mouse models of TSC. Sirolimus 37-46 TSC complex subunit 1 Mus musculus 159-162 25613864-1 2015 The genetic disease tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by loss of function mutations in either TSC1 (hamartin) or TSC2 (tuberin), which serve as negative regulators of mechanistic target of rapamycin complex 1 (mTORC1) activity. Sirolimus 229-238 TSC complex subunit 1 Mus musculus 134-138 25613864-1 2015 The genetic disease tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by loss of function mutations in either TSC1 (hamartin) or TSC2 (tuberin), which serve as negative regulators of mechanistic target of rapamycin complex 1 (mTORC1) activity. Sirolimus 229-238 TSC complex subunit 1 Mus musculus 140-148 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 TSC complex subunit 1 Mus musculus 64-67 25213336-8 2015 Rapamycin reversed the conversion from BAT to WAT in Fabp4-Tsc1(-/-) mice. Sirolimus 0-9 TSC complex subunit 1 Mus musculus 59-63 25646773-9 2015 However, liver TG levels were significantly reduced in the Tsc1-/-;Pten-/- mice compared to the Pten-/- mice, which was restored with rapamycin. Sirolimus 134-143 TSC complex subunit 1 Mus musculus 59-63 25082895-4 2014 L-Tsc1 KO mice displayed reduced locomotor activity, body temperature, and hepatic triglyceride content in a rapamycin-sensitive manner. Sirolimus 109-118 TSC complex subunit 1 Mus musculus 0-9 23386687-3 2013 Rapamycin and related drugs have been shown to have clinical benefit for these tumors in patients with TSC and those with sporadic forms of TSC-related neoplasms. Sirolimus 0-9 TSC complex subunit 1 Mus musculus 103-106 23661807-8 2013 Similarly, mice with fibroblast-specific deletion of Tsc1, a negative regulator of Rheb, exhibited activated mTORC1 signaling in kidney interstitial fibroblasts and increased renal fibrosis, both of which rapamycin abolished. Sirolimus 205-214 TSC complex subunit 1 Mus musculus 53-57 23386687-3 2013 Rapamycin and related drugs have been shown to have clinical benefit for these tumors in patients with TSC and those with sporadic forms of TSC-related neoplasms. Sirolimus 0-9 TSC complex subunit 1 Mus musculus 140-143 21212099-0 2011 Smooth muscle protein-22-mediated deletion of Tsc1 results in cardiac hypertrophy that is mTORC1-mediated and reversed by rapamycin. Sirolimus 122-131 TSC complex subunit 1 Mus musculus 46-50 23143994-5 2013 Maternal administration of rapamycin, a classical mTOR inhibitor, significantly increased the survival time of Fabp4-Tsc1cKO mice for up to 23 days. Sirolimus 27-36 TSC complex subunit 1 Mus musculus 117-121 21890496-4 2011 These observations have led us to examine the benefit of prenatal rapamycin in a new fetal brain model of TSC. Sirolimus 66-75 TSC complex subunit 1 Mus musculus 106-109 21890496-10 2011 These observations demonstrate the therapeutic benefit and limitations of prenatal rapamycin in a prenatal-onset brain model of TSC. Sirolimus 83-92 TSC complex subunit 1 Mus musculus 128-131 23335988-9 2013 In addition, rapamycin, a specific mTORC1 inhibitor, effectively rescued the phenotype caused by increased mTORC1 activity in the Tsc1(cko) ovaries. Sirolimus 13-22 TSC complex subunit 1 Mus musculus 130-134 14500340-6 2003 Moreover, short-term treatment of Tsc1+/- mice with rapamycin at 20 mg/kg led to some changes in tumor morphology and a reduction in serum VEGF levels. Sirolimus 52-61 TSC complex subunit 1 Mus musculus 34-38 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 TSC complex subunit 1 Mus musculus 24-28 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 TSC complex subunit 1 Mus musculus 32-35 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 TSC complex subunit 1 Mus musculus 32-35 19368729-6 2009 RESULTS: Here, we examine the efficacy of a prolonged maintenance dose of rapamycin in Tsc2+/- mice with TSC-related kidney tumors. Sirolimus 74-83 TSC complex subunit 1 Mus musculus 105-108 18389497-5 2008 METHODS: Tsc1(GFAP)CKO mice and littermate control animals were treated with rapamycin or vehicle starting at postnatal day 14 (early treatment) or 6 weeks of age (late treatment), corresponding to times before and after onset of neurological abnormalities in Tsc1(GFAP)CKO mice. Sirolimus 77-86 TSC complex subunit 1 Mus musculus 9-13 18389497-9 2008 RESULTS: Early treatment with rapamycin prevented the development of epilepsy and premature death observed in vehicle-treated Tsc1(GFAP)CKO mice. Sirolimus 30-39 TSC complex subunit 1 Mus musculus 126-130 18389497-10 2008 Late treatment with rapamycin suppressed seizures and prolonged survival in Tsc1(GFAP)CKO mice that had already developed epilepsy. Sirolimus 20-29 TSC complex subunit 1 Mus musculus 76-80 18389497-12 2008 INTERPRETATION: Rapamycin has strong efficacy for preventing seizures and prolonging survival in Tsc1(GFAP)CKO mice. Sirolimus 16-25 TSC complex subunit 1 Mus musculus 97-101 17290308-4 2007 This was a direct effect of mTOR activation, since rapamycin restored PDGFR expression and PDGF-sensitive Akt activation in Tsc1-/- and Tsc2-/- cells. Sirolimus 51-60 TSC complex subunit 1 Mus musculus 124-128 16845661-3 2006 The mTOR inhibitor, rapamycin (sirolimus), reduces disease severity in rodent models of TSC, and is currently in phase II clinical trials. Sirolimus 20-29 TSC complex subunit 1 Mus musculus 88-91 16845661-3 2006 The mTOR inhibitor, rapamycin (sirolimus), reduces disease severity in rodent models of TSC, and is currently in phase II clinical trials. Sirolimus 31-40 TSC complex subunit 1 Mus musculus 88-91 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 TSC complex subunit 1 Mus musculus 125-129 34365025-4 2021 Herein, we report that constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling via Tsc1 (Tuberous sclerosis 1) deletion in chondrocytes causes abnormal skull development with decreased size and rounded shape. Sirolimus 76-85 TSC complex subunit 1 Mus musculus 119-123 11875047-6 2002 Tsc1 null embryo fibroblast lines have persistent phosphorylation of the p70S6K (S6K) and its substrate S6, that is sensitive to treatment with rapamycin, indicating constitutive activation of the mTOR-S6K pathway due to loss of the Tsc1 protein, hamartin. Sirolimus 144-153 TSC complex subunit 1 Mus musculus 0-4 11875047-6 2002 Tsc1 null embryo fibroblast lines have persistent phosphorylation of the p70S6K (S6K) and its substrate S6, that is sensitive to treatment with rapamycin, indicating constitutive activation of the mTOR-S6K pathway due to loss of the Tsc1 protein, hamartin. Sirolimus 144-153 TSC complex subunit 1 Mus musculus 233-237 11875047-6 2002 Tsc1 null embryo fibroblast lines have persistent phosphorylation of the p70S6K (S6K) and its substrate S6, that is sensitive to treatment with rapamycin, indicating constitutive activation of the mTOR-S6K pathway due to loss of the Tsc1 protein, hamartin. Sirolimus 144-153 TSC complex subunit 1 Mus musculus 247-255 32890589-2 2020 The rapamycin derivative ("rapalog") everolimus, which allosterically inhibits the mTOR pathway, is approved for the treatment of partial epilepsy with spontaneous recurrent seizures (SRS) in individuals with tuberous sclerosis complex (TSC). Sirolimus 4-13 TSC complex subunit 1 Mus musculus 237-240 34365025-4 2021 Herein, we report that constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling via Tsc1 (Tuberous sclerosis 1) deletion in chondrocytes causes abnormal skull development with decreased size and rounded shape. Sirolimus 76-85 TSC complex subunit 1 Mus musculus 125-145 34677125-3 2021 Here, we find that the hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) in an RPC subset by deletion of tuberous sclerosis complex 1 (Tsc1) makes the RPCs arrive at the division limit precociously and produce Muller glia (MG) that degenerate from senescence-associated cell death. Sirolimus 64-73 TSC complex subunit 1 Mus musculus 125-153 34677125-3 2021 Here, we find that the hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) in an RPC subset by deletion of tuberous sclerosis complex 1 (Tsc1) makes the RPCs arrive at the division limit precociously and produce Muller glia (MG) that degenerate from senescence-associated cell death. Sirolimus 64-73 TSC complex subunit 1 Mus musculus 155-159 34253722-1 2021 Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, resulting in hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 128-137 TSC complex subunit 1 Mus musculus 28-31 34253722-1 2021 Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, resulting in hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 128-137 TSC complex subunit 1 Mus musculus 46-50