PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 30728291-2 2019 TSC is caused by inactivating mutations in the genes encoding TSC1/2, negative regulators of the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 117-126 TSC complex subunit 1 Homo sapiens 0-3 30988224-3 2019 As the hamartin-tuberin-complex downregulates the mechanistic/mammalian target of the rapamycin complex1 (mTORC1), dysfunction in either hamartin or tuberin induces the constitutive activation of mTORC1. Sirolimus 86-95 TSC complex subunit 1 Homo sapiens 7-15 30988224-3 2019 As the hamartin-tuberin-complex downregulates the mechanistic/mammalian target of the rapamycin complex1 (mTORC1), dysfunction in either hamartin or tuberin induces the constitutive activation of mTORC1. Sirolimus 86-95 TSC complex subunit 1 Homo sapiens 137-145 30728291-2 2019 TSC is caused by inactivating mutations in the genes encoding TSC1/2, negative regulators of the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 117-126 TSC complex subunit 1 Homo sapiens 62-68 30144504-2 2018 The TSC1 and TSC2 genes encode proteins forming a complex (TSC), which is a major regulator and suppressor of mammalian target of rapamycin complex 1 (mTORC1), a signaling complex that promotes cell growth and proliferation. Sirolimus 130-139 TSC complex subunit 1 Homo sapiens 4-8 30127391-1 2018 Tuberous sclerosis complex (TSC) is a multisystem developmental disorder caused by mutations in the TSC1 or TSC2 genes, whose protein products are negative regulators of mechanistic target of rapamycin complex 1 signaling. Sirolimus 192-201 TSC complex subunit 1 Homo sapiens 28-31 30127391-1 2018 Tuberous sclerosis complex (TSC) is a multisystem developmental disorder caused by mutations in the TSC1 or TSC2 genes, whose protein products are negative regulators of mechanistic target of rapamycin complex 1 signaling. Sirolimus 192-201 TSC complex subunit 1 Homo sapiens 100-104 30904097-4 2019 Through the discovery of the TSC1 and TSC2 genes and the signaling pathways responsible for the pathology of TSC, a new drug target called mechanistic target of rapamycin complex 1 (mTORC1) was discovered. Sirolimus 161-170 TSC complex subunit 1 Homo sapiens 29-33 30904097-4 2019 Through the discovery of the TSC1 and TSC2 genes and the signaling pathways responsible for the pathology of TSC, a new drug target called mechanistic target of rapamycin complex 1 (mTORC1) was discovered. Sirolimus 161-170 TSC complex subunit 1 Homo sapiens 29-32 30904097-5 2019 Rapamycin, an mTORC1 inhibitor, is now the only pharmacological therapy approved for the treatment of TSC. Sirolimus 0-9 TSC complex subunit 1 Homo sapiens 102-105 30144504-2 2018 The TSC1 and TSC2 genes encode proteins forming a complex (TSC), which is a major regulator and suppressor of mammalian target of rapamycin complex 1 (mTORC1), a signaling complex that promotes cell growth and proliferation. Sirolimus 130-139 TSC complex subunit 1 Homo sapiens 4-7 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 TSC complex subunit 1 Homo sapiens 146-149 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 TSC complex subunit 1 Homo sapiens 104-108 29339522-1 2018 Lymphangioleiomyomatosis (LAM), a rare disease of women, is associated with cystic lung destruction resulting from the proliferation of abnormal smooth muscle-like LAM cells with mutations in the tuberous sclerosis complex (TSC) genes TSC1 and/or TSC2 The mutant genes and encoded proteins are responsible for activation of the mechanistic target of rapamycin (mTOR), which is inhibited by sirolimus (rapamycin), a drug used to treat LAM. Sirolimus 390-399 TSC complex subunit 1 Homo sapiens 224-227 29339522-1 2018 Lymphangioleiomyomatosis (LAM), a rare disease of women, is associated with cystic lung destruction resulting from the proliferation of abnormal smooth muscle-like LAM cells with mutations in the tuberous sclerosis complex (TSC) genes TSC1 and/or TSC2 The mutant genes and encoded proteins are responsible for activation of the mechanistic target of rapamycin (mTOR), which is inhibited by sirolimus (rapamycin), a drug used to treat LAM. Sirolimus 350-359 TSC complex subunit 1 Homo sapiens 224-227 30087333-5 2018 Knockout of either TSC1 or DEPDC5 led to enhanced HIV-1 reactivation in both a T-cell line (C11) and a monocyte cell line (U1), and this enhancement could be antagonized by the mTORC1 inhibitor rapamycin. Sirolimus 194-203 TSC complex subunit 1 Homo sapiens 19-23 29559472-0 2018 Plk1-Mediated Phosphorylation of TSC1 Enhances the Efficacy of Rapamycin. Sirolimus 63-72 TSC complex subunit 1 Homo sapiens 33-37 29559472-6 2018 Tumors derived from cancer cells expressing the TSC1-S467E/S578E mutant exhibited greater sensitivity to rapamycin than those expressing WT TSC1. Sirolimus 105-114 TSC complex subunit 1 Homo sapiens 48-52 29559472-7 2018 Collectively, our data support a model in which Plk1, instead of AKT, regulates the TSC/mTORC1 pathway during mitosis, eventually regulating the efficacy of rapamycin.Significance: This seminal report shows that activation of mTORC1 can be independent of AKT during mitosis. Sirolimus 157-166 TSC complex subunit 1 Homo sapiens 84-87 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 TSC complex subunit 1 Homo sapiens 146-149 28637240-1 2017 Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by mutations in either of two genes, TSC1 or TSC2, resulting in the constitutive activation of the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 201-210 TSC complex subunit 1 Homo sapiens 28-31 28637240-1 2017 Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by mutations in either of two genes, TSC1 or TSC2, resulting in the constitutive activation of the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 201-210 TSC complex subunit 1 Homo sapiens 119-123 28771801-14 2017 Topical sirolimus appears to be both effective and well-tolerated as a treatment of facial angiofibromas in children with TSC. Sirolimus 8-17 TSC complex subunit 1 Homo sapiens 122-125 28667702-4 2017 Hamartin-Tuberin complex is involved in the phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin signal transduction pathway, and suppresses mammalian target of rapamycin complex 1 activity, which is a center for various functions. Sirolimus 107-116 TSC complex subunit 1 Homo sapiens 0-8 27225870-6 2017 In addition, combination treatment with rapamycin and resveratrol induced cell death specifically in TSC1-/- MEF cells, and not in wild-type MEFs. Sirolimus 40-49 TSC complex subunit 1 Homo sapiens 101-105 29340326-4 2018 Mammalian target of rapamycin complex 1 (mTORC1) inhibitors (e.g., sirolimus) have been found to be effective in treating TSC- or lymphangioleiomyomatosis-associated AML, but to date it is unknown whether this strategy is effective for sporadic AML. Sirolimus 67-76 TSC complex subunit 1 Homo sapiens 122-126 29340326-7 2018 Consequently, we showed that in vitro treatment with sirolimus results in significant growth inhibition of the human sporadic AML cell line SV7Tert, similar to the effect seen when the same treatment is applied to the human TSC-associated AML cell line UMBSV-tel. Sirolimus 53-62 TSC complex subunit 1 Homo sapiens 224-227 28903387-6 2017 Most importantly, rapamycin in combination with AG1295, a PDGFR inhibitor, significantly inhibited growth of TSC1/TSC2 complex-deficient cells in vitro and in vivo. Sirolimus 18-27 TSC complex subunit 1 Homo sapiens 109-113 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 TSC complex subunit 1 Homo sapiens 106-109 28367235-7 2017 Furthermore, MK-2206 increased the cytotoxicity of rapamycin in Tsc1-/- or Tsc2-/- MEFs. Sirolimus 51-60 TSC complex subunit 1 Homo sapiens 64-68 28367235-9 2017 We conclude that the combination of rapamycin and MK-2206 may be utilized as a new therapeutic regimen for TSC. Sirolimus 36-45 TSC complex subunit 1 Homo sapiens 107-110 28336152-5 2017 The gene products of TSC1/2 form a complex which at energy limiting states, down-regulates the activity of the regulator of protein synthesis, the mammalian target of rapamycin complex1 (mTORC1). Sirolimus 167-176 TSC complex subunit 1 Homo sapiens 21-27 28057888-8 2017 Re-inactivation of mTORC1 activity via rapamycin may resist hypoxia-induced cell death in TSC1 knockdown lymphocytes. Sirolimus 39-48 TSC complex subunit 1 Homo sapiens 90-94 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 TSC complex subunit 1 Homo sapiens 42-45 27862655-7 2017 Because the product of the TSC2/Tsc2 gene (tuberin) together with hamartin, the product of another TSC gene (TSC1/Tsc1), suppresses mammalian/mechanistic target of rapamycin complex 1 (mTORC1), rapalogs have been used as therapeutic drugs for TSC. Sirolimus 164-173 TSC complex subunit 1 Homo sapiens 66-74 27862655-7 2017 Because the product of the TSC2/Tsc2 gene (tuberin) together with hamartin, the product of another TSC gene (TSC1/Tsc1), suppresses mammalian/mechanistic target of rapamycin complex 1 (mTORC1), rapalogs have been used as therapeutic drugs for TSC. Sirolimus 164-173 TSC complex subunit 1 Homo sapiens 27-30 27862655-7 2017 Because the product of the TSC2/Tsc2 gene (tuberin) together with hamartin, the product of another TSC gene (TSC1/Tsc1), suppresses mammalian/mechanistic target of rapamycin complex 1 (mTORC1), rapalogs have been used as therapeutic drugs for TSC. Sirolimus 164-173 TSC complex subunit 1 Homo sapiens 109-113 27862655-7 2017 Because the product of the TSC2/Tsc2 gene (tuberin) together with hamartin, the product of another TSC gene (TSC1/Tsc1), suppresses mammalian/mechanistic target of rapamycin complex 1 (mTORC1), rapalogs have been used as therapeutic drugs for TSC. Sirolimus 164-173 TSC complex subunit 1 Homo sapiens 114-118 27862655-7 2017 Because the product of the TSC2/Tsc2 gene (tuberin) together with hamartin, the product of another TSC gene (TSC1/Tsc1), suppresses mammalian/mechanistic target of rapamycin complex 1 (mTORC1), rapalogs have been used as therapeutic drugs for TSC. Sirolimus 164-173 TSC complex subunit 1 Homo sapiens 99-102 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 TSC complex subunit 1 Homo sapiens 244-247 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 TSC complex subunit 1 Homo sapiens 42-45 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 TSC complex subunit 1 Homo sapiens 244-247 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 TSC complex subunit 1 Homo sapiens 153-156 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 TSC complex subunit 1 Homo sapiens 153-156 26693177-2 2015 The TSC1 and TSC2 proteins form a complex that inhibits mammalian target of rapamycin complex 1 (mTORC1) signaling. Sirolimus 76-85 TSC complex subunit 1 Homo sapiens 4-8 27797139-4 2016 TSC is caused by the lack of functional Tsc1-Tsc2 complex, which serves as a major cellular inhibitor of mammalian Target of Rapamycin Complex 1 (mTORC1). Sirolimus 125-134 TSC complex subunit 1 Homo sapiens 0-3 27797139-4 2016 TSC is caused by the lack of functional Tsc1-Tsc2 complex, which serves as a major cellular inhibitor of mammalian Target of Rapamycin Complex 1 (mTORC1). Sirolimus 125-134 TSC complex subunit 1 Homo sapiens 40-44 27797139-6 2016 Consequently, mTORC1 inhibitors, such as rapamycin, serve as experimental or already approved drugs for several TSC symptoms. Sirolimus 41-50 TSC complex subunit 1 Homo sapiens 112-115 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 TSC complex subunit 1 Homo sapiens 42-46 26975583-12 2016 These results indicate that an AMPK/p27 axis is promoting a survival mechanism that could explain in part the relapse of TSC tumors treated with rapamycin, exposing new avenues for designing more efficient treatments for TSC patients. Sirolimus 145-154 TSC complex subunit 1 Homo sapiens 121-124 26975583-12 2016 These results indicate that an AMPK/p27 axis is promoting a survival mechanism that could explain in part the relapse of TSC tumors treated with rapamycin, exposing new avenues for designing more efficient treatments for TSC patients. Sirolimus 145-154 TSC complex subunit 1 Homo sapiens 221-224 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 TSC complex subunit 1 Homo sapiens 81-84 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 TSC complex subunit 1 Homo sapiens 125-128 27493206-2 2016 The gene products hamartin and tuberin form the TSC complex that acts as GTPase-activating protein for Rheb and negatively regulates the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 157-166 TSC complex subunit 1 Homo sapiens 18-26 27493206-2 2016 The gene products hamartin and tuberin form the TSC complex that acts as GTPase-activating protein for Rheb and negatively regulates the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 157-166 TSC complex subunit 1 Homo sapiens 48-51 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 TSC complex subunit 1 Homo sapiens 49-53 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 TSC complex subunit 1 Homo sapiens 55-63 26449264-2 2015 This multi-organ disorder results from inactivating point mutations in either the TSC1 or the TSC2 genes and consequent activation of the canonical mammalian target of rapamycin complex 1 signalling (mTORC1) pathway. Sirolimus 168-177 TSC complex subunit 1 Homo sapiens 82-86 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 TSC complex subunit 1 Homo sapiens 33-36 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 TSC complex subunit 1 Homo sapiens 148-151 25738543-3 2015 The protein complex TSC1/2 has been reported to have an inhibitory function on mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 99-108 TSC complex subunit 1 Homo sapiens 20-26 26356487-6 2015 With LPS + rapamycin monocytes from patients with TSC showed gene expression patterns different from healthy subjects. Sirolimus 11-20 TSC complex subunit 1 Homo sapiens 50-53 26356487-8 2015 CONCLUSION: The effects of LPS, even more of LPS with rapamycin on monocytes from patients with TSC suggested that inflammatory processes are distinct from those in healthy subjects. Sirolimus 54-63 TSC complex subunit 1 Homo sapiens 96-99 26060906-8 2015 Mutations in the TSC1 and TSC2 genes that cause tuberous sclerosis lead to hyperactivation of signaling via the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 132-141 TSC complex subunit 1 Homo sapiens 17-21 26051878-8 2015 Inhibitors of mTORC1, such as rapamycin, effectively suppress the symptoms of TSC. Sirolimus 30-39 TSC complex subunit 1 Homo sapiens 78-81 25814705-8 2015 Sirolimus has been used as a targeted therapy for the renal and neurological manifestations of TSC. Sirolimus 0-9 TSC complex subunit 1 Homo sapiens 95-98 25582464-1 2014 OBJECTIVE: To evaluate the therapeutic effect and safety of rapamycin in treatment of children with tuberous sclerosis complex (TSC) complicated with epilepsy. Sirolimus 60-69 TSC complex subunit 1 Homo sapiens 128-131 25580270-8 2014 From these data, the concept evolved that a combination of sirolimus with disruption of Rho activity with statins (e.g. simvastatin) may increase TSC-null cell death and reduce LAM cell survival. Sirolimus 59-68 TSC complex subunit 1 Homo sapiens 146-149 24889507-2 2014 Tsc1 and Tsc2 proteins form a complex that inhibits mammalian target of rapamycin complex 1 (mTORC1) signalling through Rheb-GTPase. Sirolimus 72-81 TSC complex subunit 1 Homo sapiens 0-4 25380949-3 2014 mTOR inhibitors (mTOR-I, rapamycin/everolimus) may correct underlying defects in TSC. Sirolimus 25-34 TSC complex subunit 1 Homo sapiens 81-84 25380949-4 2014 Previous data prove benefits and safety of mTOR-I on a wide spectrum of disease manifestations and effectiveness of rapamycin in TSC patients after kidney transplantation (KT). Sirolimus 116-125 TSC complex subunit 1 Homo sapiens 129-132 24599401-2 2014 TSC1/2 protein complex negatively regulates the mammalian target of rapamycin complex 1 (mTORC1) a master regulator of protein synthesis, cell growth and autophagy. Sirolimus 68-77 TSC complex subunit 1 Homo sapiens 0-6 24558502-6 2014 Rapamycin, a mTOR inhibitor, is effective in treating TSC-associated angiofibromas. Sirolimus 0-9 TSC complex subunit 1 Homo sapiens 54-57 24714658-1 2014 The TSC1-TSC2-TBC1D7 complex is an important negative regulator of the mechanistic target of rapamycin complex 1 that controls cell growth in response to environmental cues. Sirolimus 93-102 TSC complex subunit 1 Homo sapiens 4-8 24486221-9 2014 Rapamycin, an mTOR inhibitor, has been used successfully in Tsc-deficient mice to prevent and treat seizures and behavioral abnormalities. Sirolimus 0-9 TSC complex subunit 1 Homo sapiens 60-63 22532572-3 2012 Hamartin and tuberin form a heterodimer that inhibits the mammalian target of rapamycin complex 1 (mTORC1) kinase, a major cellular regulator of protein translation, cell growth and proliferation. Sirolimus 78-87 TSC complex subunit 1 Homo sapiens 0-8 24304514-7 2014 Thus, the addition of resveratrol to rapamycin treatment may be a promising option for selective and targeted therapy for diseases with TSC loss and mTORC1 hyperactivation. Sirolimus 37-46 TSC complex subunit 1 Homo sapiens 136-139 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 TSC complex subunit 1 Homo sapiens 113-116 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 TSC complex subunit 1 Homo sapiens 128-131 23446718-8 2013 Antagonism of the mTOR pathway with rapamycin and everolimus may provide new therapeutic options for these TSC patients. Sirolimus 36-45 TSC complex subunit 1 Homo sapiens 107-110 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 TSC complex subunit 1 Homo sapiens 127-130 22532572-4 2012 Hyperactivated mTORC1 signaling, an important feature of TSC, has prompted a number of preclinical and clinical studies with the mTORC1 inhibitor rapamycin. Sirolimus 146-155 TSC complex subunit 1 Homo sapiens 57-60 22532572-6 2012 We hypothesized that low-dose rapamycin given prenatally and/or postnatally in a well-established neuroglial (Tsc2-hGFAP) model of TSC would rescue brain developmental defects. Sirolimus 30-39 TSC complex subunit 1 Homo sapiens 131-134 22532572-12 2012 These results have important translational implications in the optimization of the timing and dosage of rapamycin treatment in TSC affected children. Sirolimus 104-113 TSC complex subunit 1 Homo sapiens 127-130 21907282-12 2012 The dramatic effect of rapamycin suggests that even with extensive multi-lineage abnormalities, a postnatal therapeutic window may exist for patients with TSC. Sirolimus 23-32 TSC complex subunit 1 Homo sapiens 155-158 21874011-4 2012 It has been demonstrated that most of these lesions are determined by mutations affecting genes of the tuberous sclerosis complex, tuberous sclerosis 1 (TSC1) and tuberous sclerosis 2 (TSC2), with eventual deregulation of the RHEB/MTOR/RPS6KB2 pathway, and it has been observed that some PEComas regressed during sirolimus therapy, an MTOR inhibitor. Sirolimus 313-322 TSC complex subunit 1 Homo sapiens 131-151 21874011-4 2012 It has been demonstrated that most of these lesions are determined by mutations affecting genes of the tuberous sclerosis complex, tuberous sclerosis 1 (TSC1) and tuberous sclerosis 2 (TSC2), with eventual deregulation of the RHEB/MTOR/RPS6KB2 pathway, and it has been observed that some PEComas regressed during sirolimus therapy, an MTOR inhibitor. Sirolimus 313-322 TSC complex subunit 1 Homo sapiens 153-157 22025691-8 2011 Postnatal rapamycin treatment completely reversed these phenotypes and rescued the mutants from epilepsy and premature death, despite prenatal onset of Tsc1 loss and mTOR complex 1 activation in the developing brain. Sirolimus 10-19 TSC complex subunit 1 Homo sapiens 152-156 21692771-0 2011 A topical combination of rapamycin and tacrolimus for the treatment of angiofibroma due to tuberous sclerosis complex (TSC): a pilot study of nine Japanese patients with TSC of different disease severity. Sirolimus 25-34 TSC complex subunit 1 Homo sapiens 119-122 21692771-3 2011 Although rapamycin improves many TSC lesions, significant side-effects appear after systemic administration. Sirolimus 9-18 TSC complex subunit 1 Homo sapiens 33-36 21692771-5 2011 OBJECTIVES: The efficacy of rapamycin-tacrolimus ointment was examined for TSC-related angiofibroma. Sirolimus 28-37 TSC complex subunit 1 Homo sapiens 75-78 21692771-11 2011 CONCLUSIONS: Topical application of rapamycin-tacrolimus ointment is a safe and useful treatment for TSC-related angiofibroma. Sirolimus 36-45 TSC complex subunit 1 Homo sapiens 101-104 20566381-1 2010 Inhibition of mTOR by rapamycin has been shown to suppress seizures in TSC/PTEN genetic models. Sirolimus 22-31 TSC complex subunit 1 Homo sapiens 71-74 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 TSC complex subunit 1 Homo sapiens 66-72 21530413-3 2011 Recently, understanding the neurobiology of hamartin and tuberin in the development of epilepsy and cognitive impairment associated with tuberous sclerosis complex allowed the development of sirolimus and everolimus to be used in human clinical trials. Sirolimus 191-200 TSC complex subunit 1 Homo sapiens 44-52 20146692-6 2010 Antagonism of the mTOR pathway with rapamycin and related compounds may provide new therapeutic options for TSC patients. Sirolimus 36-45 TSC complex subunit 1 Homo sapiens 108-111 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 TSC complex subunit 1 Homo sapiens 147-150 20087180-4 2010 RECENT FINDINGS: In this review, I discuss the basic science findings that position the TSC1 and TSC2 genes as critical regulators of the mammalian target of rapamycin kinase within mammalian target of rapamycin complex 1. Sirolimus 158-167 TSC complex subunit 1 Homo sapiens 88-92 20087180-4 2010 RECENT FINDINGS: In this review, I discuss the basic science findings that position the TSC1 and TSC2 genes as critical regulators of the mammalian target of rapamycin kinase within mammalian target of rapamycin complex 1. Sirolimus 202-211 TSC complex subunit 1 Homo sapiens 88-92 19966866-8 2010 Rapamycin may have unique benefit for patients with lung cancer, for whom the TSC1/TSC2 function is limited. Sirolimus 0-9 TSC complex subunit 1 Homo sapiens 78-82 20235887-4 2010 However, these Tsc rodent models have been useful in confirming the two-hit model of tumor development in TSC, and in providing systems in which therapeutic trials (e.g., rapamycin) can be performed. Sirolimus 171-180 TSC complex subunit 1 Homo sapiens 15-18 19694899-5 2009 CONCLUSIONS: Results suggest that reversing the underlying molecular deficits of TSC with rapamycin or other mTOR inhibitors could result in clinically significant improvements of cognitive function and neurological symptoms, even if treatments are started in adulthood. Sirolimus 90-99 TSC complex subunit 1 Homo sapiens 81-84 20924998-11 2010 Oral rapamycin therapy may induce regression of astrocytomas associated with TSC. Sirolimus 5-14 TSC complex subunit 1 Homo sapiens 77-80 19917366-1 2009 Herein we have reported the use of rapamycin in immunosuppressive treatment after renal transplantation as a therapy of choice in a patient with diagnosis of tuberous sclerosis complex (TSC). Sirolimus 35-44 TSC complex subunit 1 Homo sapiens 186-189 19917366-13 2009 Experimental and clinical studies have confirmed that rapamycin exerts beneficial effects in TSC, providing a new therapeutic option. Sirolimus 54-63 TSC complex subunit 1 Homo sapiens 93-96 19917366-14 2009 Therefore an immunosuppressive regimen with rapamycin should be considered as the treatment of choice after kidney transplantation among patients with TSC seeking to avoid development or progression of disease complications. Sirolimus 44-53 TSC complex subunit 1 Homo sapiens 151-154 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 TSC complex subunit 1 Homo sapiens 179-183 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 TSC complex subunit 1 Homo sapiens 116-119 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 1 Homo sapiens 38-41 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 1 Homo sapiens 38-41 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 TSC complex subunit 1 Homo sapiens 297-300 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 TSC complex subunit 1 Homo sapiens 31-34 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 TSC complex subunit 1 Homo sapiens 121-124 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 TSC complex subunit 1 Homo sapiens 4-8 19297407-3 2009 The gene products of TSC1 and TSC2, also known as hamartin and tuberin, respectively, form a physical and functional complex and inhibit the mammalian target of rapamycin complex 1 (mTORC1) signaling. Sirolimus 161-170 TSC complex subunit 1 Homo sapiens 21-25 19297407-3 2009 The gene products of TSC1 and TSC2, also known as hamartin and tuberin, respectively, form a physical and functional complex and inhibit the mammalian target of rapamycin complex 1 (mTORC1) signaling. Sirolimus 161-170 TSC complex subunit 1 Homo sapiens 50-58 18350576-1 2008 OBJECTIVE: Genetic loss of TSC1/TSC2 function in tuberous sclerosis complex (TSC) results in overactivation of the mammalian target of rapamycin complex 1 pathway, leading to cellular dysplasia. Sirolimus 135-144 TSC complex subunit 1 Homo sapiens 27-31 18350576-1 2008 OBJECTIVE: Genetic loss of TSC1/TSC2 function in tuberous sclerosis complex (TSC) results in overactivation of the mammalian target of rapamycin complex 1 pathway, leading to cellular dysplasia. Sirolimus 135-144 TSC complex subunit 1 Homo sapiens 27-30 17637444-9 2007 Special attention is paid in this work to TSC treatment options, including therapeutic trials with rapamycin, also known as sirolimus. Sirolimus 124-133 TSC complex subunit 1 Homo sapiens 42-45 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 TSC complex subunit 1 Homo sapiens 118-121 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 TSC complex subunit 1 Homo sapiens 118-121 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 TSC complex subunit 1 Homo sapiens 25-29 17179073-12 2007 We discuss the complex genetic interactions between tor1(+), tor2(+), and tsc1/2(+) and the implications for rapamycin sensitivity in tsc1 or tsc2 mutants. Sirolimus 109-118 TSC complex subunit 1 Homo sapiens 134-138 17179073-11 2007 Mutants lacking Tsc1 or Tsc2 are highly sensitive to rapamycin under poor nitrogen conditions, suggesting that the function of Tor1 under such conditions is sensitive to rapamycin. Sirolimus 53-62 TSC complex subunit 1 Homo sapiens 16-20 17179073-11 2007 Mutants lacking Tsc1 or Tsc2 are highly sensitive to rapamycin under poor nitrogen conditions, suggesting that the function of Tor1 under such conditions is sensitive to rapamycin. Sirolimus 170-179 TSC complex subunit 1 Homo sapiens 16-20 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 TSC complex subunit 1 Homo sapiens 133-136 16412252-12 2006 TSC1/TSC2 mutant cell lines administered Rapamycin blocked S6 phorphorylation and diminished the levels of HIF-1alpha to those observed in cell lines with wild type TSC1/TSC2. Sirolimus 41-50 TSC complex subunit 1 Homo sapiens 0-4 16412252-12 2006 TSC1/TSC2 mutant cell lines administered Rapamycin blocked S6 phorphorylation and diminished the levels of HIF-1alpha to those observed in cell lines with wild type TSC1/TSC2. Sirolimus 41-50 TSC complex subunit 1 Homo sapiens 165-169 16244323-7 2005 As a specific inhibitor of mTOR, rapamycin has therapeutic potential for the treatment of TSC hamartomas. Sirolimus 33-42 TSC complex subunit 1 Homo sapiens 90-93 15150095-5 2004 A combination of IFN-gamma and rapamycin is markedly synergistic in induction of apoptosis in Tsc1 or Tsc2 null cells because pSTAT3 Tyr705 phosphorylation is abolished completely and the other effects of IFN-gamma are maintained or enhanced. Sirolimus 31-40 TSC complex subunit 1 Homo sapiens 94-98 15150095-6 2004 Rapamycin-IFN-gamma has unique potential therapeutic benefit for management of TSC tumors. Sirolimus 0-9 TSC complex subunit 1 Homo sapiens 79-82 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 TSC complex subunit 1 Homo sapiens 97-100 12773161-3 2003 Hamartin and tuberin form a complex and antagonise phosphoinositide 3-kinase/protein kinase B/target of rapamycin signal transduction by inhibiting p70 S6 kinase, an activator of translation, and activating 4E-binding protein 1, an inhibitor of translation initiation. Sirolimus 104-113 TSC complex subunit 1 Homo sapiens 0-8 14500340-5 2003 Rapamycin, a mTOR inhibitor, reduced the production of VEGF by Tsc1- and Tsc2-null fibroblasts to normal levels. Sirolimus 0-9 TSC complex subunit 1 Homo sapiens 63-67 14607085-3 2003 Together, these genetic, biochemical and cell-biological studies have demonstrated that the tuberin-hamartin complex inhibits target of rapamycin (TOR) signaling by acting as a GTPase-activating protein for the Ras-related small G protein Rheb. Sirolimus 136-145 TSC complex subunit 1 Homo sapiens 100-108 33773987-3 2021 Rapamycin (sirolimus) shrinks TSC tumors but clinical benefits of sirolimus are not sustained after its withdrawal. Sirolimus 0-9 TSC complex subunit 1 Homo sapiens 30-33 12384518-7 2002 Our data provide in vivo evidence that the mTOR pathway is aberrantly activated in TSC renal pathology and that treatment with rapamycin appears effective in the preclinical setting. Sirolimus 127-136 TSC complex subunit 1 Homo sapiens 83-86 33773987-3 2021 Rapamycin (sirolimus) shrinks TSC tumors but clinical benefits of sirolimus are not sustained after its withdrawal. Sirolimus 11-20 TSC complex subunit 1 Homo sapiens 30-33 33773987-9 2021 These results suggest that sirolimus may decrease the size of TSC tumors by reducing TSC2-/- cell volume, altering cell cycle and reprogramming TSC2-null cells. Sirolimus 27-36 TSC complex subunit 1 Homo sapiens 62-65 34806651-1 2021 Mutations underlying disease in tuberous sclerosis complex (TSC) give rise to tumors with biallelic mutations in TSC1 or TSC2 and hyperactive mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 162-171 TSC complex subunit 1 Homo sapiens 60-63 34349839-1 2021 Tuberous sclerosis complex (TSC) is a rare genetic disorder caused by mutations in the TSC1 or TSC2 genes, which encode proteins that antagonise the mammalian isoform of the target of rapamycin complex 1 (mTORC1) - a key mediator of cell growth and metabolism. Sirolimus 184-193 TSC complex subunit 1 Homo sapiens 28-31 34544857-1 2021 Tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM) are caused by aberrant mechanistic Target of Rapamycin Complex 1 (mTORC1) activation due to loss of either TSC1 or TSC2 Cytokine profiling of TSC2-deficient LAM patient-derived cells revealed striking up-regulation of Interleukin-6 (IL-6). Sirolimus 113-122 TSC complex subunit 1 Homo sapiens 28-31 34301883-1 2021 Tuberous sclerosis complex 1 (Tsc1) is a tumor suppressor that functions together with Tsc2 to negatively regulate the mechanistic target of rapamycin complex 1 (mTORC1) activity. Sirolimus 141-150 TSC complex subunit 1 Homo sapiens 0-28 34301883-1 2021 Tuberous sclerosis complex 1 (Tsc1) is a tumor suppressor that functions together with Tsc2 to negatively regulate the mechanistic target of rapamycin complex 1 (mTORC1) activity. Sirolimus 141-150 TSC complex subunit 1 Homo sapiens 30-34 34778262-2 2021 In response to nutrient shortage and stresses, the TSC complex inhibits the mechanistic target of rapamycin complex 1 (mTORC1) at the lysosomes. Sirolimus 98-107 TSC complex subunit 1 Homo sapiens 51-54 34853810-1 2021 Loss of function of tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) leads to the activation of mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 116-125 TSC complex subunit 1 Homo sapiens 55-59 34349839-1 2021 Tuberous sclerosis complex (TSC) is a rare genetic disorder caused by mutations in the TSC1 or TSC2 genes, which encode proteins that antagonise the mammalian isoform of the target of rapamycin complex 1 (mTORC1) - a key mediator of cell growth and metabolism. Sirolimus 184-193 TSC complex subunit 1 Homo sapiens 87-91 33891611-2 2021 Mutation and loss of function of TSC1 and/or TSC2 also occur in a variety of sporadic cancers, and rapamycin and related drugs show highly variable treatment benefit in patients with such cancers. Sirolimus 99-108 TSC complex subunit 1 Homo sapiens 33-37 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 TSC complex subunit 1 Homo sapiens 337-340 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 TSC complex subunit 1 Homo sapiens 54-57 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 TSC complex subunit 1 Homo sapiens 133-137 33910008-1 2021 Recent studies have demonstrated that selective activation of mammalian target of rapamycin complex 1 (mTORC1) in the cerebellum by deletion of the mTORC1 upstream repressors TSC1 or phosphatase and tensin homolog (PTEN) in Purkinje cells (PCs) causes autism-like features and cognitive deficits. Sirolimus 82-91 TSC complex subunit 1 Homo sapiens 175-179 34178631-4 2021 We also aimed to investigate the effect of the FDA approved drug rapamycin and the vitamin A metabolite retinoic acid (RA) in cell lines with TSC mutation. Sirolimus 65-74 TSC complex subunit 1 Homo sapiens 142-145 34178631-11 2021 Combination of the two FDA approved drugs -RA for acute myeloid leukaemia and rapamycin for TSC mutation- normalised ALDH and ADH expression and activity, restored RARbeta expression and reduced cellular proliferation and migration. Sirolimus 78-87 TSC complex subunit 1 Homo sapiens 92-95 34178631-14 2021 Based on our data, translational studies could confirm whether combination of RA with reduced dosage of rapamycin would have more beneficial effects to higher dosage of rapamycin monotherapy meanwhile reducing adverse effects of rapamycin for patients with TSC mutation. Sirolimus 229-238 TSC complex subunit 1 Homo sapiens 257-260 35596872-10 2022 Treatment with anti-seizure medication (ASM) or in combination with rapamycin results in clinical remission in most patients with TSC-associated seizures (14/15). Sirolimus 68-77 TSC complex subunit 1 Homo sapiens 130-133 35483522-6 2022 Genetic deletion of the Tuberous sclerosis 1 gene in kidney glomerular podocytes activated mammalian target of rapamycin complex 1 signaling to rpS6 phosphorylation, resulting in podocyte hypertrophy and pathologic features similar to those of patients with FSGS including podocyte loss, leading to segmental glomerulosclerosis. Sirolimus 111-120 TSC complex subunit 1 Homo sapiens 24-44 35359647-1 2022 Objective: Tuberous sclerosis complex (TSC) is a genetic disease that arises from TSC1 or TSC2 abnormalities and induces the overactivation of the mammalian/mechanistic target of rapamycin pathways. Sirolimus 179-188 TSC complex subunit 1 Homo sapiens 39-42 35246210-5 2022 Although mTOR inhibitors (rapamycin/everolimus) demonstrate great potential in TSC management, two major concerns hamper their generalized application. Sirolimus 26-35 TSC complex subunit 1 Homo sapiens 79-82 33902956-0 2021 Sirolimus-based immunosuppression improves the prognosis of liver Transplantation Recipients with low TSC1/2 expression in hepatocellular carcinoma beyond the Milan Criteria. Sirolimus 0-9 TSC complex subunit 1 Homo sapiens 102-108 33902956-11 2021 Subgroup (TSC1-based or TSC2-based) analyses revealed that patients with low TSC1 or TSC2 expression benefited from sirolimus (DFS: P = 0.046, OS: P = 0.006 for TSC1; DFS: P = 0.05, OS: P = 0.003 for TSC2) compared with patients with high expression. Sirolimus 116-125 TSC complex subunit 1 Homo sapiens 77-81 33902956-11 2021 Subgroup (TSC1-based or TSC2-based) analyses revealed that patients with low TSC1 or TSC2 expression benefited from sirolimus (DFS: P = 0.046, OS: P = 0.006 for TSC1; DFS: P = 0.05, OS: P = 0.003 for TSC2) compared with patients with high expression. Sirolimus 116-125 TSC complex subunit 1 Homo sapiens 77-81 33902956-12 2021 TSC1 knockdown in Huh-7 and Bel-7402 HCC cell lines activated the mTORC1 pathway and enhanced cell proliferation, migration and sensitivity to SRL in vitro and in vivo. Sirolimus 143-146 TSC complex subunit 1 Homo sapiens 0-4 33902956-13 2021 CONCLUSION: TSC1/2 expression could be used to predict the prognosis of patients with HCC beyond the Milan criteria who underwent SRL-based immunosuppression following LT. TSC1 knockdown promoted HCC malignancy and enhanced sensitivity to SRL. Sirolimus 130-133 TSC complex subunit 1 Homo sapiens 12-18 33902956-13 2021 CONCLUSION: TSC1/2 expression could be used to predict the prognosis of patients with HCC beyond the Milan criteria who underwent SRL-based immunosuppression following LT. TSC1 knockdown promoted HCC malignancy and enhanced sensitivity to SRL. Sirolimus 130-133 TSC complex subunit 1 Homo sapiens 12-16 33902956-13 2021 CONCLUSION: TSC1/2 expression could be used to predict the prognosis of patients with HCC beyond the Milan criteria who underwent SRL-based immunosuppression following LT. TSC1 knockdown promoted HCC malignancy and enhanced sensitivity to SRL. Sirolimus 239-242 TSC complex subunit 1 Homo sapiens 12-18 33902956-13 2021 CONCLUSION: TSC1/2 expression could be used to predict the prognosis of patients with HCC beyond the Milan criteria who underwent SRL-based immunosuppression following LT. TSC1 knockdown promoted HCC malignancy and enhanced sensitivity to SRL. Sirolimus 239-242 TSC complex subunit 1 Homo sapiens 12-16 33860865-5 2021 The study also reveals that treatment of TSC mutant cells with the drug candidate Proxison combined with reduced concentration of rapamycin can increase production of reactive oxygen species (ROS), can modify miRNA expression pattern associated with p53 regulation and can reduce cell viability. Sirolimus 130-139 TSC complex subunit 1 Homo sapiens 41-44 32761379-4 2020 The identification of TSC1 and TSC2, as tumor suppressor genes causative of the disorder, led to the elucidation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway and its pivotal role in the pathogenesis of hamartoma formation. Sirolimus 140-149 TSC complex subunit 1 Homo sapiens 22-26 33923449-1 2021 Tuberous sclerosis complex (TSC) is a genetic disorder caused by inactivating mutations in TSC1 (hamartin) or TSC2 (tuberin), crucial negative regulators of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. Sirolimus 183-192 TSC complex subunit 1 Homo sapiens 28-31 33923449-1 2021 Tuberous sclerosis complex (TSC) is a genetic disorder caused by inactivating mutations in TSC1 (hamartin) or TSC2 (tuberin), crucial negative regulators of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. Sirolimus 183-192 TSC complex subunit 1 Homo sapiens 91-95 33923449-1 2021 Tuberous sclerosis complex (TSC) is a genetic disorder caused by inactivating mutations in TSC1 (hamartin) or TSC2 (tuberin), crucial negative regulators of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. Sirolimus 183-192 TSC complex subunit 1 Homo sapiens 97-105 33923449-8 2021 Rapamycin efficiently decreased mTORC1 activity of these TSC1-deficient cells in vitro. Sirolimus 0-9 TSC complex subunit 1 Homo sapiens 57-61 33923449-9 2021 In vivo, TSC1-deficient cells could form SEGA-like tumors and Rapamycin treatment decreased tumor growth. Sirolimus 62-71 TSC complex subunit 1 Homo sapiens 9-13 33307091-1 2021 The Tuberous Sclerosis Complex (TSC) protein complex (TSCC), comprising TSC1, TSC2, and TBC1D7, is widely recognised as a key integration hub for cell growth and intracellular stress signals upstream of the mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 227-236 TSC complex subunit 1 Homo sapiens 72-76 33398801-1 2021 Tuberous sclerosis complex (TSC) is a dominant autosomal genetic disorder caused by loss-of-function mutations in TSC1 and TSC2, which lead to constitutive activation of the mammalian target of rapamycin C1 (mTORC1) with its decoupling from regulatory inputs. Sirolimus 194-203 TSC complex subunit 1 Homo sapiens 28-31 33398801-1 2021 Tuberous sclerosis complex (TSC) is a dominant autosomal genetic disorder caused by loss-of-function mutations in TSC1 and TSC2, which lead to constitutive activation of the mammalian target of rapamycin C1 (mTORC1) with its decoupling from regulatory inputs. Sirolimus 194-203 TSC complex subunit 1 Homo sapiens 114-118 33658088-2 2021 Mutations in the TSC1 or TSC2 genes have been reported to cause disruption in the TSC1-TSC2 intracellular protein complex, causing over-activation of the mammalian target of rapamycin protein complex. Sirolimus 174-183 TSC complex subunit 1 Homo sapiens 17-21 33658088-2 2021 Mutations in the TSC1 or TSC2 genes have been reported to cause disruption in the TSC1-TSC2 intracellular protein complex, causing over-activation of the mammalian target of rapamycin protein complex. Sirolimus 174-183 TSC complex subunit 1 Homo sapiens 82-86 33431351-4 2021 Rapamycin has been widely used in different animal models of TSC-related epilepsy and proved to be able not only to suppress seizures but also to prevent the development of epilepsy, thus demonstrating an antiepileptogenic potential. Sirolimus 0-9 TSC complex subunit 1 Homo sapiens 61-64 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 TSC complex subunit 1 Homo sapiens 22-30 31869431-1 2020 AIMS: Oxidative stress is evident in resected epileptogenic brain tissue of patients with developmental brain malformations related to mammalian target of rapamycin activation: tuberous sclerosis complex (TSC) and focal cortical dysplasia type IIb (FCD IIb). Sirolimus 155-164 TSC complex subunit 1 Homo sapiens 205-208 32739207-2 2020 As an important negative regulatory factor of the mammalian target of rapamycin complex 1 (mTORC1) signal, tuberous sclerosis complex 1 (Tsc1) is also a key regulatory point of glycolysis. Sirolimus 70-79 TSC complex subunit 1 Homo sapiens 107-135 32927859-1 2020 TSC1 is a tumor suppressor that inhibits cell growth via negative regulation of the mammalian target of rapamycin complex (mTORC1). Sirolimus 104-113 TSC complex subunit 1 Homo sapiens 0-4 32739207-2 2020 As an important negative regulatory factor of the mammalian target of rapamycin complex 1 (mTORC1) signal, tuberous sclerosis complex 1 (Tsc1) is also a key regulatory point of glycolysis. Sirolimus 70-79 TSC complex subunit 1 Homo sapiens 137-141 32502382-1 2020 The TSC complex is the cognate GTPase-activating protein (GAP) for the small GTPase Rheb and a crucial regulator of the mechanistic target of rapamycin complex 1 (mTORC1). Sirolimus 142-151 TSC complex subunit 1 Homo sapiens 4-7 32765227-4 2020 Inactivating mutations in TSC genes (TSC1/TSC2) cause sustained Ras homologue enriched in brain (RHEB) activation of the mammalian isoform of the target of rapamycin complex 1 (mTORC1). Sirolimus 156-165 TSC complex subunit 1 Homo sapiens 26-29 32765227-4 2020 Inactivating mutations in TSC genes (TSC1/TSC2) cause sustained Ras homologue enriched in brain (RHEB) activation of the mammalian isoform of the target of rapamycin complex 1 (mTORC1). Sirolimus 156-165 TSC complex subunit 1 Homo sapiens 37-41 32469097-7 2020 Supplementing miR-196b-5p activity in progenitor cells reduced the protein level of TSC1 and activated mammalian target of rapamycin complex 1 (mTORC1) signaling. Sirolimus 123-132 TSC complex subunit 1 Homo sapiens 84-88 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 TSC complex subunit 1 Homo sapiens 41-45 32579942-1 2020 Tuberous sclerosis complex (TSC) is a neurogenetic disorder that leads to elevated mechanistic targeting of rapamycin complex 1 (mTORC1) activity. Sirolimus 108-117 TSC complex subunit 1 Homo sapiens 28-31 31921404-0 2020 TSC patient-derived isogenic neural progenitor cells reveal altered early neurodevelopmental phenotypes and rapamycin-induced MNK-eIF4E signaling. Sirolimus 108-117 TSC complex subunit 1 Homo sapiens 0-3 31958214-2 2020 The main etiology of TSC is the loss-of-function mutation of TSC1 or TSC2 gene, which leads to aberrant activation of mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 138-147 TSC complex subunit 1 Homo sapiens 21-24 31958214-2 2020 The main etiology of TSC is the loss-of-function mutation of TSC1 or TSC2 gene, which leads to aberrant activation of mammalian target of rapamycin complex 1 (mTORC1). Sirolimus 138-147 TSC complex subunit 1 Homo sapiens 61-65 31958214-8 2020 In addition, combination of rapamycin with PFK15, a PFKFB3 inhibitor, exerts a stronger inhibitory effect on cell proliferation of Tsc1- or Tsc2-null MEFs than treatment with single drug. Sirolimus 28-37 TSC complex subunit 1 Homo sapiens 131-135 31958214-9 2020 We conclude that loss of TSC1 or TSC2 led to upregulated expression of PFKFB3 through activation of mTORC1/HIF-1alpha signaling pathway and co-administration of rapamycin and PFK15 may be a promising strategy for the treatment of TSC tumors as well as other hyperactivated mTORC1-related tumors. Sirolimus 161-170 TSC complex subunit 1 Homo sapiens 25-29 31958214-9 2020 We conclude that loss of TSC1 or TSC2 led to upregulated expression of PFKFB3 through activation of mTORC1/HIF-1alpha signaling pathway and co-administration of rapamycin and PFK15 may be a promising strategy for the treatment of TSC tumors as well as other hyperactivated mTORC1-related tumors. Sirolimus 161-170 TSC complex subunit 1 Homo sapiens 25-28 31921404-2 2020 The aberrant activation of mTORC1 in TSC has led to treatment with mTORC1 inhibitor rapamycin as a lifelong therapy for tumors, but TSC-associated neurocognitive manifestations remain unaffected by rapamycin. Sirolimus 84-93 TSC complex subunit 1 Homo sapiens 37-40 31921404-9 2020 In TSC1-Het and Null NPCs, we also observed basal activation of ERK1/2, which was further activated upon rapamycin treatment. Sirolimus 105-114 TSC complex subunit 1 Homo sapiens 3-7 31921404-10 2020 Rapamycin also increased MNK1/2-eIF4E signaling in TSC1-deficient NPCs. Sirolimus 0-9 TSC complex subunit 1 Homo sapiens 51-55 31921404-12 2020 Our data showing upregulation of these signaling pathways by rapamycin support a strategy to combine a MEK or a MNK inhibitor with rapamycin that may be superior for TSC-associated CNS defects. Sirolimus 61-70 TSC complex subunit 1 Homo sapiens 166-169 31665839-1 2019 Objective: To investigate the efficacy and safety of rapamycin in children with tuberous sclerosis complex (TSC) associated renal disease. Sirolimus 53-62 TSC complex subunit 1 Homo sapiens 108-111 31665839-15 2019 Conclusions: Rapamycin could decrease the diameter of TSC-related RAML, but could not inhibit the growth of cysts. Sirolimus 13-22 TSC complex subunit 1 Homo sapiens 54-57 31834371-1 2020 Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited neurocutaneous disorder caused by inactivating mutations in TSC1 or TSC2, key regulators of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Sirolimus 188-197 TSC complex subunit 1 Homo sapiens 28-31 31834371-1 2020 Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited neurocutaneous disorder caused by inactivating mutations in TSC1 or TSC2, key regulators of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Sirolimus 188-197 TSC complex subunit 1 Homo sapiens 130-134