PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 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 2 Mus musculus 9-13 33159078-6 2020 Mesenchymal-restricted deletion of Tsc2 in the mouse lung produces a mTORC1-driven pulmonary phenotype, with a progressive disruption of alveolar structure, a decline in pulmonary function, increase of rapamycin-sensitive expression of WNT ligands, and profound female-specific changes in mesenchymal and epithelial lung cell gene expression. Sirolimus 202-211 TSC complex subunit 2 Mus musculus 35-39 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 2 Mus musculus 58-62 32781001-9 2020 AA levels and rapamycin differentially modulate S6 and 4E-BP1 phosphorylation and mTOR lysosomal localization in neurons following Tsc2 KO versus Depdc5 KO. Sirolimus 14-23 TSC complex subunit 2 Mus musculus 131-135 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 2 Mus musculus 144-148 32191726-6 2020 Rapamycin attenuated podocyte dysfunction and extends survival in Tsc2Deltapodocyte mice. Sirolimus 0-9 TSC complex subunit 2 Mus musculus 66-70 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 2 Mus musculus 23-27 31207499-6 2019 Both AZD2014 and rapamycin potently suppressed EMT of renal tumors and effectively blocked tumor progression in Tsc2+/- mice. Sirolimus 17-26 TSC complex subunit 2 Mus musculus 112-116 31182914-0 2019 Feedback Activation of SGK3 and AKT Contributes to Rapamycin Resistance by Reactivating mTORC1/4EBP1 Axis via TSC2 in Breast Cancer. Sirolimus 51-60 TSC complex subunit 2 Mus musculus 110-114 29396625-5 2018 Hedgehog signaling was restored in Tsc1-/- cells after exogenous expression of Gli2, whereas rapamycin restored HH signaling in Tsc2-/- cells. Sirolimus 93-102 TSC complex subunit 2 Mus musculus 128-132 30816188-6 2019 We developed the first Tsc2-null rapamycin-resistant cell line, ELT3-245, which is highly tumorigenic in mice, and refractory to rapamycin treatment. Sirolimus 33-42 TSC complex subunit 2 Mus musculus 23-27 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 2 Mus musculus 231-235 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 2 Mus musculus 153-157 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 2 Mus musculus 55-59 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 2 Mus musculus 94-98 24632604-0 2015 Renal tumours in a Tsc2(+/-) mouse model do not show feedback inhibition of Akt and are effectively prevented by rapamycin. Sirolimus 113-122 TSC complex subunit 2 Mus musculus 19-23 24632604-10 2015 In conclusion, in contrast to previous studies, we found that Akt signalling is not inhibited in Tsc-associated renal lesions and that by partially inhibiting the Akt/mTOR pathway, rapamycin is highly effective in preventing Tsc-associated tumours. Sirolimus 181-190 TSC complex subunit 2 Mus musculus 225-228 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 2 Mus musculus 104-108 27278252-9 2016 In addition, treatment of mice deficient in tuberin with rapamycin resulted in significant decrease in all Nox protein expression. Sirolimus 57-66 TSC complex subunit 2 Mus musculus 44-51 26854565-6 2016 Using a large-scale, unbiased quantitative proteomic platform, we comprehensively characterized the rapamycin-sensitive secretome in TSC2(-/-) mouse embryonic fibroblasts, and identified IGFBP5 as a secreted, mTORC1 downstream effector protein. Sirolimus 100-109 TSC complex subunit 2 Mus musculus 133-137 24931163-3 2015 We show that rapamycin reduces HIF-1alpha protein levels, and to a lesser extent VEGF-A levels, in renal cystadenoma cells in a Tsc2+/- mouse model. Sirolimus 13-22 TSC complex subunit 2 Mus musculus 128-132 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 2 Mus musculus 159-166 21802234-5 2012 One Tsc2(+/-) mouse was treated with rapamycin for two months after the initial scan. Sirolimus 37-46 TSC complex subunit 2 Mus musculus 4-8 23081885-4 2014 Then, we show that Tsc2 shRNA knockdown (KD) in mouse neural progenitor cells (mNPCs) in vitro results in enhanced mTORC1 (phospho-S6, phospho-4E-BP1) and mTORC2 (phospho-Akt and phospho-NDRG1) signaling, as well as a doubling of cell size that is rescued by rapamycin, an mTORC1 inhibitor. Sirolimus 259-268 TSC complex subunit 2 Mus musculus 19-23 23081885-5 2014 Tsc2 KD in vivo in the fetal mouse brain by in utero electroporation causes disorganized cortical lamination and increased cell volume that is prevented with rapamycin. Sirolimus 158-167 TSC complex subunit 2 Mus musculus 0-4 23035046-7 2012 The combination of rapamycin and simvastatin prevented both growth of TSC2-null lesions and lung destruction by inhibiting MMP-2, MMP-3, and MMP-9. Sirolimus 19-28 TSC complex subunit 2 Mus musculus 70-74 25155956-5 2014 The mTOR inhibitor rapamycin corrected ASD-like behaviors and spine pruning defects in Tsc2 +- mice, but not in Atg7(CKO) neuronal autophagy-deficient mice or Tsc2 +- :Atg7(CKO) double mutants. Sirolimus 19-28 TSC complex subunit 2 Mus musculus 87-91 21802234-10 2012 By MRI, these lesions demonstrated significant growth in the 9 untreated Tsc1(+/-) and Tsc2(+/-) mice but shrinkage in the rapamycin treated Tsc2(+/-) mouse. Sirolimus 123-132 TSC complex subunit 2 Mus musculus 141-145 20146790-0 2010 Comparison of three rapamycin dosing schedules in A/J Tsc2+/- mice and improved survival with angiogenesis inhibitor or asparaginase treatment in mice with subcutaneous tuberous sclerosis related tumors. Sirolimus 20-29 TSC complex subunit 2 Mus musculus 54-58 20656472-10 2010 In contrast, transfection of Tsc2(+/-) cells with DN-S6K abolished p70S6K phosphorylation and increased OGG1 expression, a response enhanced by rapamycin. Sirolimus 144-153 TSC complex subunit 2 Mus musculus 29-33 20656472-11 2010 Treatment of Tsc2(+/-) mice with rapamycin resulted in activation of AMPK, downregulation of phospho-p70S6K and enhanced OGG1 expression. Sirolimus 33-42 TSC complex subunit 2 Mus musculus 13-17 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 2 Mus musculus 43-47 20656472-2 2010 In early clinical trials, tuberous sclerosis complex (TSC)-related kidney tumours were found to regress following rapamycin treatment. Sirolimus 114-123 TSC complex subunit 2 Mus musculus 54-57 20656472-4 2010 Treatment of HK2 cells, mouse Tsc-deficient cells and human VHL-deficient cells (786-O) with rapamycin resulted in decrease in p70S6K phosphorylation at Thr(389), and increase in the expression of NF-YA and OGG1 proteins. Sirolimus 93-102 TSC complex subunit 2 Mus musculus 30-33 20159776-8 2010 In response to artery injury using a carotid artery ligation model, Tsc2(+/-) mice significantly increased neointima formation compared with the control mice, and the neointima formation was inhibited by treatment with rapamycin. Sirolimus 219-228 TSC complex subunit 2 Mus musculus 68-72 20146790-2 2010 Rapamycin has been shown to reduce the size of kidney angiomyolipomas associated with TSC; however, tumor regression is incomplete and kidney angiomyolipomas regrow after cessation of treatment. Sirolimus 0-9 TSC complex subunit 2 Mus musculus 86-89 20146790-9 2010 When rapamycin dosing schedules were compared in A/J Tsc2+/- cohorts, we observed a 66% reduction in kidney tumor burden in mice treated daily for 4 weeks, an 82% reduction in mice treated daily for 4 weeks followed by weekly for 8 weeks, and an 81% reduction in mice treated weekly for 12 weeks. Sirolimus 5-14 TSC complex subunit 2 Mus musculus 53-57 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 2 Mus musculus 133-137 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 2 Mus musculus 136-140 19539245-6 2009 Investigation of this hypothesis in a TSC cell model revealed that mTOR suppression with an mTOR inhibitor, rapamycin (sirolimus), led to up-regulation of ERK/MAPK signaling in mouse Tsc2 knockout cells and that this augmented signaling was attenuated by concurrent administration of a MEK1/2 inhibitor, PD98059. Sirolimus 108-117 TSC complex subunit 2 Mus musculus 183-187 19539245-6 2009 Investigation of this hypothesis in a TSC cell model revealed that mTOR suppression with an mTOR inhibitor, rapamycin (sirolimus), led to up-regulation of ERK/MAPK signaling in mouse Tsc2 knockout cells and that this augmented signaling was attenuated by concurrent administration of a MEK1/2 inhibitor, PD98059. Sirolimus 119-128 TSC complex subunit 2 Mus musculus 183-187 19420259-5 2009 In Tsc2-deficient neurons, the expression of stress markers such as CHOP and HO-1 is increased, and this increase is completely reversed by the mTOR inhibitor rapamycin both in vitro and in vivo. Sirolimus 159-168 TSC complex subunit 2 Mus musculus 3-7 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 2 Mus musculus 87-91 19368729-9 2009 We observed a 94.5% reduction in kidney tumor burden in Tsc2+/- mice treated (part one) daily with rapamycin (8 mg/kg) at 6 months