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R0395 Sigma

Rapamycin from Streptomyces hygroscopicus

≥95% (HPLC), powder

Synonym: 23,27-Epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine, AY 22989, Sirolimus

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Description

Frequently Asked Questions

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Biochem/physiol Actions

A macrocyclic triene antibiotic that binds to and inhibits the molecular target of rapamycin (mTOR). It forms a complex with FKBP12 that binds to and inhibits the molecular target of rapamycin (mTOR). Rapamycin is a potent immunosuppressant and has anticancer activity.

Features and Benefits

This compound is featured on the PKB/Akt page of the Handbook of Receptor Classification and Signal Transduction. To browse other handbook pages, click here.

This compound was developed by Pfizer. To browse the list of other pharma-developed compounds and Approved Drugs/Drug Candidates, click here.

Protocols & Applications

Antibiotic Selector for application, solubility, solution stability, working concentration, and mode of action information

Price and Availability

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Safety & Documentation

Protocols & Articles

Articles

Oncogenes and Tumor Suppressors Reprogram Metabolism

Proliferating cells require the biosynthesis of structural components for biomass production and for genomic replication. This requires a reprogramming of the metabolic pathways to ensure nutrients s...
Keywords: Aerobic, Antitumor agents, Apoptosis, Biofiles, Cancer, Citric Acid Cycle, Degradations, Environmental, Events, Gene expression, Glycolysis, Growth factors, Metabolic Pathways, Metabolism, Metabolites, Nucleotide Synthesis, PAGE, Pentose phosphate pathway, Phosphorylations, Support

The Cancer Stem Cell Hypothesis

Traditionally, cancer has been viewed as a disease in which environmental or endogenous events induce mutations to critical oncogenes and tumor suppressor genes within a normal cell. The clinical man...
Vicki Caligur
BioFiles 2008, 3.5, 4.
Keywords: Angiogenesis, Apoptosis, Asymmetric synthesis, Cancer, Catalysis, Cell culture, Cell division, Cell proliferation, Clinical, DNA replication, Degradations, Eliminations, Environmental, Events, Gastrointestinal, Gene expression, Growth factors, Ligands, Metabolic Pathways, Phosphorylations, Poisons, Transcription, Transfection, transformation

Peer-Reviewed Papers

References

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Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford Progeria Syndrome cells. Cao, K. et al. Sci. Transl. Med. 3, (2011)

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Upstream of the mammalian target of rapamycin; do all roads pass through mTOR? Corradetti MN, and Guan KL. Oncogene 25, 6347-6360, (2006)

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Activation of mammalian target of rapamycin and synaptogenesis: role in the actions of rapid-acting antidepressants. Dwyer JM and Duman RS Biol. Psychiatry 73(12), 1189-98, (2013)

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Bare metal stents, durable polymer drug eluting stents, and biodegradable polymer drug eluting stents for coronary artery disease: mixed treatment comparison meta-analysis. Bangalore S, Toklu B, Amoroso N, et al. BMJ 347, f6625, (2013)

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Chemical injury-induced corneal opacity and neovascularization reduced by rapamycin via TGF-β1/ERK pathways regulation. Shin YJ, Hyon JY, Choi WS, et al. Invest. Ophthalmol. Vis. Sci. 54(7), 4452-8, (2013)

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Biodegradable polymer biolimus-eluting stent versus durable polymer everolimus-eluting stent: a randomized, controlled, noninferiority trial. Natsuaki M, Kozuma K, Morimoto T, et al. J. Am. Coll. Cardiol. 62(3), 181-90, (2013)

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Degradation Of Regulator Of Calcineurin 1 (RCAN1) Is Mediated By Both Chaperone-mediated Autophagy And Ubiquitin Proteasome Pathways. Liu, H., et al. FASEB J. 23, 3383-92, (2009)

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A comprehensive review of everolimus clinical reports: a new mammalian target of rapamycin inhibitor. Gurk-Turner C, Manitpisitkul W, and Cooper M Transplantation 94(7), 659-68, (2012)

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Current understanding of the molecular biology of pancreatic neuroendocrine tumors. Zhang J, Francois R, Iyer R, et al. J. Natl. Cancer Inst. 105(14), 1005-17, (2013)

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TOR Complex 2 Controls Gene Silencing, Telomere Length Maintenance, And Survival Under DNA-damaging Conditions. Schonbrun, M., et al. Mol. Cell. Biol. 29, 4584-94, (2009)

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Both PI3K- and mTOR-signaling pathways take part in CVB3-induced apoptosis of Hela cells. Li X, Zhang J, Chen Z, et al. DNA Cell. Biol. 32(7), 359-70, (2013)

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Phase II study of temsirolimus (CCI-779) in women with recurrent, unresectable, locally advanced or metastatic carcinoma of the cervix. A trial of the NCIC Clinical Trials Group (NCIC CTG IND 199). Tinker AV, Ellard S, Welch S, et al. Gynecol. Oncol. 130(2), 269-74, (2013)

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Lipid droplet and early autophagosomal membrane targeting of Atg2A and Atg14L in human tumor cells. Pfisterer SG, Bakula D, Frickey T, et al. J. Lipid Res. 55(7), 1267-1278, (2014)

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Ageing research: Blood to blood. Scudellari M Nature 517(7535), 426-9, (2015)

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Hypersensitivity reaction in the US Food and Drug Administration-approved second-generation drug-eluting stents: histopathological assessment with ex vivo optical coherence tomography. Otsuka F, Yahagi K, Ladich E, et al. Circulation 131(3), 322-4, (2015)

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Intravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial. Petrou PA, Cunningham D, Shimel K, et al. Invest. Ophthalmol. Vis. Sci. 56(1), 330-8, (2015)

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What the Human Genome Project hasn't told us: the epigenetics of development of esophageal squamous cell cancer. Ferraris VA J. Thorac. Cardiovasc. Surg. 149(1), 386-7, (2015)

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Enhanced Longevity by Ibuprofen, Conserved in Multiple Species, Occurs in Yeast through Inhibition of Tryptophan Import. He C, Tsuchiyama SK, Nguyen QT, et al. PLoS Genet. 10(12), e1004860, (2014)

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Long-term outcome of sirolimus-eluting and zotarolimus-eluting coronary stent implantation in patients with and without diabetes mellitus (a Danish organization for randomized trials on clinical outcome III substudy). Olesen KK, Tilsted HH, Jensen LO, et al. Am. J. Cardiol. 115(3), 298-302, (2015)

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Chronic sirolimus therapy for lymphangioleiomyomatosis. McCormack FX Am. J. Respir. Crit. Care Med. 190(12), 1332-3, (2014)

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Translational Medicine. A target for pharmacological intervention in an untreatable human disease. Johnson SC Science 346(6214), 1192, (2014)

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Long-term favorable coronary healing after bioresorbable scaffold implantation: insights from OCT. Gonzalo N, Dangas G, and Ibanez B J. Am. Coll. Cardiol. 64(22), 2357-9, (2014)

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OCT assessment of the long-term vascular healing response 5 years after everolimus-eluting bioresorbable vascular scaffold. Karanasos A, Simsek C, Gnanadesigan M, et al. J. Am. Coll. Cardiol. 64(22), 2343-56, (2014)

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Everolimus for subependymal giant cell astrocytoma in patients with tuberous sclerosis complex: 2-year open-label extension of the randomised EXIST-1 study. Franz DN, Belousova E, Sparagana S, et al. Lancet Oncol. 15(13), 1513-20, (2014)

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The mTOR inhibitor revolution rolls on. Northrup H Lancet Oncol. 15(13), 1418-9, (2014)

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Topical rapamycin combined with pulsed dye laser in the treatment of capillary vascular malformations in Sturge-Weber syndrome: phase II, randomized, double-blind, intraindividual placebo-controlled clinical trial. Marqués L, Núñez-Córdoba JM, Aguado L, et al. J. Am. Acad. Dermatol. 72(1), 151-8.e1, (2015)

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Effects of mTOR inhibition on normal retinal vascular development in the mouse. Yagasaki R, Nakahara T, Mori A, et al. Exp. Eye Res. 129, 127-34, (2014)

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The dual mTORC1 and mTORC2 inhibitor PP242 shows strong antitumor activity in a pheochromocytoma PC12 cell tumor model. Zhang X, Wang X, Qin L, et al. Urology 85(1), 273.e1-7, (2015)

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The 4E-BP1/eIF4E ratio is a determinant for rapamycin response in esophageal cancer cells. Hsu HS, Lin MH, Jang YH, et al. J. Thorac. Cardiovasc. Surg. 149(1), 378-85, (2015)

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Phase I clinical trial of temsirolimus and vinorelbine in advanced solid tumors. Piatek CI, Raja GL, Ji L, et al. Cancer Chemother. Pharmacol. 74(6), 1227-34, (2014)

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Pet dogs set to test anti-ageing drug. Check Hayden E Nature 514(7524), 546, (2014)

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Rapamycin protection of livers from ischemia and reperfusion injury is dependent on both autophagy induction and mammalian target of rapamycin complex 2-Akt activation. Zhu J, Lu T, Yue S, et al. Transplantation 99(1), 48-55, (2015)

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Cellular factors promoting resistance to effective treatment of glioma with oncolytic myxoma virus. Zemp FJ, McKenzie BA, Lun X, et al. Cancer Res. 74(24), 7260-73, (2014)

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Sustained effects of sirolimus on lung function and cystic lung lesions in lymphangioleiomyomatosis. Yao J, Taveira-DaSilva AM, Jones AM, et al. Am. J. Respir. Crit. Care Med. 190(11), 1273-82, (2014)

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A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy. Ronan B, Flamand O, Vescovi L, et al. Nat. Chem. Biol. 10(12), 1013-9, (2014)

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Inhibition of the mTORC pathway in the antiphospholipid syndrome. Van Laecke S, Nagler EV, and Vanholder R N. Engl. J. Med. 371(16), 1553, (2014)

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Inhibition of the mTORC pathway in the antiphospholipid syndrome. Canaud G and Terzi F N. Engl. J. Med. 371(16), 1554-5, (2014)

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Response and acquired resistance to everolimus in anaplastic thyroid cancer. Wagle N, Grabiner BC, Van Allen EM, et al. N. Engl. J. Med. 371(15), 1426-33, (2014)

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Changes in the diffusion capacity for carbon monoxide and the development of non-infectious pneumonitis in patients with metastatic renal cell carcinoma treated with everolimus. Park K, Kim HJ, Lee JL, et al. Anticancer Res. 34(10), 5723-8, (2014)

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A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions (ABSORB II): an interim 1-year analysis of clinical and procedural secondary outcomes from a randomised controlled trial. Serruys PW, Chevalier B, Dudek D, et al. Lancet 385(9962), 43-54, (2015)

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Biodegradable stents: the golden future of angioplasty? Di Mario C and Caiazzo G Lancet 385(9962), 10-2, (2015)

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Compelling results of adjuvant therapy with sirolimus for severe H1N1 pneumonia. Chuang YC, Ruan SY, and Huang CT Crit. Care Med. 42(10), e687-8, (2014)

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Revisiting the BIOSCIENCE of drug-eluting stent technology. Mehilli J and Massberg S Lancet 384(9960), 2086-8, (2014)

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Ultrathin strut biodegradable polymer sirolimus-eluting stent versus durable polymer everolimus-eluting stent for percutaneous coronary revascularisation (BIOSCIENCE): a randomised, single-blind, non-inferiority trial. Pilgrim T, Heg D, Roffi M, et al. Lancet 384(9960), 2111-22, (2014)

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Retrospective review of combined sirolimus and simvastatin therapy in lymphangioleiomyomatosis. Taveira-DaSilva AM, Jones AM, Julien-Williams PA, et al. Chest 147(1), 180-7, (2015)

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Stent thrombosis in early-generation drug-eluting stents versus newer-generation everolimus-eluting stent assorted by LVEF. van Boven N, Windecker S, Umans VA, et al. Heart 101(1), 50-7, (2015)

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4EBP1/eIF4E and p70S6K/RPS6 axes play critical and distinct roles in hepatocarcinogenesis driven by AKT and N-Ras proto-oncogenes in mice. Wang C, Cigliano A, Jiang L, et al. Hepatology 61(1), 200-13, (2015)

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Pharmacological inhibition of coronary restenosis: systemic and local approaches. Guerra E, Byrne RA, and Kastrati A Expert Opin. Pharmacother. 15(15), 2155-71, (2014)

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RIST: a potent new combination therapy for glioblastoma. Nonnenmacher L, Westhoff MA, Fulda S, et al. Int. J. Cancer 136(4), E173-87, (2015)

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Phase 1 and pharmacokinetic study of everolimus in combination with cetuximab and carboplatin for recurrent/metastatic squamous cell carcinoma of the head and neck. Saba NF, Hurwitz SJ, Magliocca K, et al. Cancer 120(24), 3940-51, (2014)

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Pharmacodynamic monitoring of mammalian target of rapamycin inhibition by phosphoflow cytometric determination of p70S6 kinase activity. Hoerning A, Wilde B, Wang J, et al. Transplantation 99(1), 210-9, (2015)

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A randomized 2×2 factorial trial, part 1: single-dose rabbit antithymocyte globulin induction may improve renal transplantation outcomes. Stevens RB, Foster KW, Miles CD, et al. Transplantation 99(1), 197-209, (2015)

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Bioenergetic adaptation in response to autophagy regulators during rotenone exposure. Giordano S, Dodson M, Ravi S, et al. J. Neurochem. 131(5), 625-33, (2014)

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Medical treatment of advanced thoracic neuroendocrine tumors. Ferolla P Thorac. Surg. Clin. 24(3), 351-5, (2014)

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Leptin modulates autophagy in human CD4+CD25- conventional T cells. Cassano S, Pucino V, La Rocca C, et al. Metabolism 63(10), 1272-9, (2014)

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Reconsideration of age as a contraindication for curative therapy of sickle cell disease. King AA and DiPersio JF JAMA 312(1), 33-4, (2014)

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The mTORC pathway in the antiphospholipid syndrome. Eikelboom JW and Weitz JI N. Engl. J. Med. 371(4), 369-71, (2014)

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Identification and expression analysis of the zebrafish orthologues of the mammalian MAP1LC3 gene family. Ganesan S, Moussavi Nik SH, Newman M, et al. Exp. Cell Res. 328(1), 228-37, (2014)

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The pharmacokinetics of everolimus in de novo kidney transplant patients receiving tacrolimus: an analysis from the randomized ASSET study. Rostaing L, Christiaans MH, Kovarik JM, et al. Ann. Transplant. 19, 337-45, (2014)

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The antiviral immune response in human conventional dendritic cells is controlled by the mammalian target of rapamycin. Fekete T, Pazmandi K, Szabo A, et al. J. Leukoc. Biol. 96(4), 579-89, (2014)

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Acute respiratory distress attributed to sirolimus in solid organ transplant recipients. Wang WL and Yu LX Am. J. Emerg. Med. 33(1), 124.e1-4, (2015)

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The regulatory T cell effector molecule fibrinogen-like protein 2 is necessary for the development of rapamycin-induced tolerance to fully MHC-mismatched murine cardiac allografts. Urbanellis P, Shyu W, Khattar R, et al. Immunology 144(1), 91-106, (2015)

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Rapamycin does not inhibit human cytomegalovirus reactivation from dendritic cells in vitro. Glover TE, Kew VG, and Reeves MB J. Gen. Virol. 95(Pt 10), 2260-6, (2014)

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Safety and efficacy of the early introduction of everolimus with reduced-exposure cyclosporine a in de novo kidney recipients. Oh CK, Huh KH, Ha J, et al. Transplantation 99(1), 180-6, (2015)

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Calcineurin inhibitor-free graft-versus-host disease prophylaxis with sirolimus and mycophenolate mofetil in a second allogeneic stem cell transplantation for engraftment failure and rituximab-refractory Epstein-Barr virus-induced posttransplant lymphoproliferative disease. Ceppi F, Duval M, Teira P, et al. J. Pediatr. Hematol. Oncol. 36(5), e319-21, (2014)

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Effects of obesity on transcriptomic changes and cancer hallmarks in estrogen receptor-positive breast cancer. Fuentes-Mattei E, Velazquez-Torres G, Phan L, et al. J. Natl. Cancer Inst. 106(7), doi:10.1093/jnci/dju158, (2014)

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YM155 reverses rapamycin resistance in renal cancer by decreasing survivin. Koike H, Nitta T, Sekine Y, et al. J. Cancer Res. Clin. Oncol. 140(10), 1705-13, (2014)

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Illuminating and alarming insights into vascular healing. Lavi S and Camuglia AC Can. J. Cardiol. 30(8), 855-7, (2014)

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News products to avoid. Prescrire Int. 23(148), 105, (2014)

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A randomized comparison of platinum chromium-based everolimus-eluting stents versus cobalt chromium-based Zotarolimus-Eluting stents in all-comers receiving percutaneous coronary intervention: HOST-ASSURE (harmonizing optimal strategy for treatment of coronary artery stenosis-safety & effectiveness of drug-eluting stents & anti-platelet regimen), a randomized, controlled, noninferiority trial. Park KW, Kang SH, Kang HJ, et al. J. Am. Coll. Cardiol. 63(25 Pt A), 2805-16, (2014)

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When is downstream pathway inhibition important? Wilson S and Chia SK Lancet Oncol. 15(6), 541-2, (2014)

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Temsirolimus combined with cisplatin or bevacizumab is active in osteosarcoma models. Fleuren ED, Versleijen-Jonkers YM, Roeffen MH, et al. Int. J. Cancer 135(12), 2770-82, (2014)

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Inhibition of mTOR down-regulates scavenger receptor, class B, type I (SR-BI) expression, reduces endothelial cell migration and impairs nitric oxide production. Fruhwürth S, Krieger S, Winter K, et al. Biochim. Biophys. Acta 1841(7), 944-53, (2014)

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Mammalian target of rapamycin: a novel pathway in vascular calcification. Montezano AC and Touyz RM Can. J. Cardiol. 30(5), 482-4, (2014)

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Control of thrombotic thrombocytopenic purpura by sirolimus in a child with juvenile myelomonocytic leukemia and somatic N-RAS mutation. Maschan M, Bobrynina V, Khachatryan L, et al. Pediatr. Blood Cancer 61(10), 1871-3, (2014)

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Flavaglines target primitive leukemia cells and enhance anti-leukemia drug activity. Callahan KP, Minhajuddin M, Corbett C, et al. Leukemia 28(10), 1960-8, (2014)

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[A case of massive pancreatic neuroendocrine carcinoma successfully treated with surgical resection and postoperative everolimus administration]. Mukai Y, Takeda Y, Nakahira S, et al. Gan To Kagaku Ryoho. 40(12), 1887-9, (2013)

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Invited commentary. Bhorade S Ann. Thorac. Surg. 97(1), 274-5, (2014)

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Medicine. A common pathway for a rare disease? Vafai SB and Mootha VK Science 342(6165), 1453-4, (2013)

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Needs for monitoring mosquito transmission of malaria in a pre-elimination world. James S, Takken W, Collins FH, et al. Am. J. Trop. Med. Hyg. 90(1), 6-10, (2014)

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Response of subependymal giant cell astrocytoma with spinal cord metastasis to everolimus. Aguilera D, Flamini R, Mazewski C, et al. J. Pediatr. Hematol. Oncol. 36(7), e448-51, (2014)

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Biomedicine. A putative antiaging drug takes a step from mice to men. Leslie M Science 342(6160), 789, (2013)

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Drug-eluting stent trials: too much non-inferiority, too little progress? Byrne RA and Kastrati A Lancet 383(9915), 386-8, (2014)

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Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and human immunodeficiency. Lucas CL, Kuehn HS, Zhao F, et al. Nat. Immunol. 15(1), 88-97, (2014)

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mTORC1 phosphorylation sites encode their sensitivity to starvation and rapamycin. Kang SA, Pacold ME, Cervantes CL, et al. Science 341(6144), 1236566, (2013)

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FIM-A, a phosphorus-containing sirolimus, inhibits the angiogenesis and proliferation of osteosarcomas. Liu WN, Lin JH, Cheng YR, et al. Oncol. Res. 20(7), 319-26, (2013)

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Combination of rapamycin and imatinib in treating refractory chronic myeloid leukemia myeloid blast crisis:a case report(025B3;). Xie J, Zhang X, Fang BZ, et al. Chin. Med. Sci. J. 28(2), 127-8, (2013)

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Results of an international randomized phase III trial of the mammalian target of rapamycin inhibitor ridaforolimus versus placebo to control metastatic sarcomas in patients after benefit from prior chemotherapy. Demetri GD, Chawla SP, Ray-Coquard I, et al. J. Clin. Oncol. 31(19), 2485-92, (2013)

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[An advance in the management of breast cancer]. Soins. (774), 12, (2013)

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It may be possible to delay the onset of neurodegenerative diseases with an immunosuppressive drug (rapamycin). Aso E and Ferrer I Expert Opin. Biol. Ther. 13(9), 1215-9, (2013)

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Mammalian target of rapamycin (mTOR) pathways in neurological diseases. Wong M Biomed. J. 36(2), 40-50, (2013)

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Chronic mechanistic target of rapamycin inhibition: preventing cancer to delay aging, or vice versa?. Sharp ZD, Curiel TJ, and Livi CB Interdiscip. Top. Gerontol. 38, 1-16, (2013)

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mTOR as a positive regulator of tumor cell responses to hypoxia. Abraham, R.T. Curr. Top. Microbiol. Immunol. 279, 299-319, (2004)

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Integration of growth factor and nutrient signaling: implications for cancer biology. Shamji, A.F., et al. Mol. Cell. 12, 271-280, (2003)

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Lkb1/Stk11 regulation of mTOR signaling controls the transition of chondrocyte fates and suppresses skeletal tumor formation. Lai LP, Lilley BN, Sanes JR, et al. Proc. Natl. Acad. Sci. U. S. A. 110(48), 19450-5, (2013)

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Myc and mTOR converge on a common node in protein synthesis control that confers synthetic lethality in Myc-driven cancers. Pourdehnad M, Truitt ML, Siddiqi IN, et al. Proc. Natl. Acad. Sci. U. S. A. 110(29), 11988-93, (2013)

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Mitonuclear protein imbalance as a conserved longevity mechanism. Houtkooper RH, Mouchiroud L, Ryu D, et al. Nature 497(7450), 451-7, (2013)

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A zebrafish model of chordoma initiated by notochord-driven expression of HRASV12. Burger A, Vasilyev A, Tomar R, et al. Dis. Model Mech. 7(7), 907-13, (2014)

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PI3K-Akt signaling activates mTOR-mediated epileptogenesis in organotypic hippocampal culture model of post-traumatic epilepsy. Berdichevsky Y, Dryer AM, Saponjian Y, et al. J. Neurosci. 33(21), 9056-67, (2013)

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Wound healing complications and the use of mammalian target of rapamycin inhibitors in kidney transplantation: a critical review of the literature. Nashan B and Citterio F Transplantation 94(6), 547-61, (2012)

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Targeting the mTOR signaling network in cancer Chiang GG, and Abraham RT. Trends Mol. Med. 13, 433-442, (2007)

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Possible prevention of tuberous sclerosis complex lesions. Kotulska K, Borkowska J, and Jozwiak S Pediatrics 132(1), e239-42, (2013)

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Everolimus-eluting stents in patients undergoing percutaneous coronary intervention: final 3-year results of the Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Subjects With de Novo Native Coronary Artery Lesions trial. Brener SJ, Kereiakes DJ, Simonton CA, et al. Am. Heart J. 166(6), 1035-42, (2013)

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Safety and efficacy outcomes of first and second generation durable polymer drug eluting stents and biodegradable polymer biolimus eluting stents in clinical practice: comprehensive network meta-analysis. Navarese EP, Tandjung K, Claessen B, et al. BMJ 347, f6530, (2013)

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Three vs twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. Feres F, Costa RA, Abizaid A, et al. JAMA 310(23), 2510-22, (2013)

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Systematic characterization of the conformation and dynamics of budding yeast chromosome XII. Albert B, Mathon J, Shukla A, et al. J. Cell Biol. 202(2), 201-10, (2013)

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Effect of visceral metastases on the efficacy and safety of everolimus in postmenopausal women with advanced breast cancer: subgroup analysis from the BOLERO-2 study. Campone M, Bachelot T, Gnant M, et al. Eur. J. Cancer 49(12), 2621-32, (2013)

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mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome. Johnson SC, Yanos ME, Kayser EB, et al. Science 342(6165), 1524-8, (2013)

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Leukemia inhibitory factor promotes nasopharyngeal carcinoma progression and radioresistance. Liu SC, Tsang NM, Chiang WC, et al. J. Clin. Invest. 123(12), 5269-83, (2013)

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Involvement of PI3K/Akt/TOR pathway in stretch-induced hypertrophy of myotubes. Sasai, N., et al. Muscle Nerve 41, 100-6, (2010)

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Randomized comparison of Zotarolimus-Eluting Endeavor Sprint versus bare-metal stent implantation in uncertain drug-eluting stent candidates: rationale, design, and characterization of the patient population for the Zotarolimus-eluting Endeavor Sprint stent in uncertain DES candidates study. Valgimigli M, Patialiakas A, Thury A, et al. Am. Heart J. 166(5), 831-8, (2013)

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The molecular target of rapamycin (mTOR) as a therapeutic target against cancer. Mita, MM, et al. Cancer Biol. Ther. 2, S169-S177, (2003)

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The molecular target of rapamycin (mTOR) as a therapeutic target against cancer. Mita, MM, et al. Cancer Biol. Ther. 2, S169-S177, (2003)

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Phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway inhibition: a breakthrough in the management of luminal (ER+/HER2-) breast cancers? Zardavas D, Fumagalli D, and Loi S Curr. Opin. Oncol. 24(6), 623-34, (2012)

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Evidence for rapamycin toxicity in pancreatic β-cells and a review of the underlying molecular mechanisms. Barlow AD, Nicholson ML, and Herbert TP Diabetes 62(8), 2674-82, (2013)

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Targeting mTOR with rapamycin; One dose does not fit all Foster DA, Toschi A. Cell Cycle 2, 8, (2009)

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RTOG 0913: a phase 1 study of daily everolimus (RAD001) in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma. Chinnaiyan P, Won M, Wen PY, et al. Int. J. Radiat. Oncol. Biol. Phys. 86(5), 880-4, (2013)

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Metabolic regulation, mitochondria and the life-prolonging effect of rapamycin: a mini-review. Pan Y, Nishida Y, Wang M, et al. Gerontology 58(6), 524-30, (2012)

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Outcomes in ethnic minority renal transplant recipients receiving everolimus versus mycophenolate: comparative risk assessment results from a pooled analysis. Melancon K, Mulgaonkar SP, Delcoro C, et al. Transplantation 96(12), 1073-81, (2013)

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The Mammalian target of rapamycin inhibitors in breast cancer: current evidence and future directions. Malaguti P, Vari S, Cognetti F, et al. Anticancer Res. 33(1), 21-8, (2013)

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A randomized, open-label study of sirolimus versus cyclosporine in primary de novo renal allograft recipients. Flechner SM, Gurkan A, Hartmann A, et al. Transplantation 95(10), 1233-41, (2013)

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Time dependency of outcomes for drug-eluting vs bare-metal stents. Leung AA, Southern DA, Galbraith PD, et al. Can. J. Cardiol. 29(12), 1616-22, (2013)

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Role of inhibitors of mammalian target of rapamycin in the treatment of luminal breast cancer. Ciruelos E, Cortes-Funes H, Ghanem I, et al. Anticancer Drugs 24(8), 769-80, (2013)

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Bone effects of mammalian target of rapamycin (mTOR) inhibition with everolimus. Hadji P, Coleman R, and Gnant M Crit. Rev. Oncol. Hematol. 87(2), 101-11, (2013)

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Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial. Zhu AX, Kudo M, Assenat E, et al. JAMA 312(1), 57-67, (2014)

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A phase Ib study investigating the combination of everolimus and dovitinib in vascular endothelial growth factor refractory clear cell renal cancer. Powles T, Foreshew SJ, Shamash J, et al. Eur. J. Cancer 50(12), 2057-64, (2014)

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Persistent long-term facilitation at an identified synapse becomes labile with activation of short-term heterosynaptic plasticity. Hu JY and Schacher S J. Neurosci. 34(14), 4776-85, (2014)

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Rapamycin-mediated CD36 translational suppression contributes to alleviation of hepatic steatosis. Wang C, Yan Y, Hu L, et al. Biochem. Biophys. Res. Commun. 447(1), 57-63, (2014)

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Rapamycin limits the growth of established experimental abdominal aortic aneurysms. Rouer M, Xu BH, Xuan HJ, et al. Eur. J. Vasc. Endovasc. Surg. 47(5), 493-500, (2014)

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Temsirolimus and chloroquine cooperatively exhibit a potent antitumor effect against colorectal cancer cells. Kaneko M, Nozawa H, Hiyoshi M, et al. J. Cancer Res. Clin. Oncol. 140(5), 769-81, (2014)

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Everolimus for patients with mantle cell lymphoma refractory to or intolerant of bortezomib: multicentre, single-arm, phase 2 study. Wang M, Popplewell LL, Collins RH, et al. Br. J. Haematol. 165(4), 510-8, (2014)

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mTOR inhibitors and their clinical application in cervical, endometrial and ovarian cancers: a critical review. Husseinzadeh N and Husseinzadeh HD Gynecol. Oncol. 133(2), 375-81, (2014)

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Mammalian target of rapamycin inhibitor-associated stomatitis. Boers-Doets CB, Raber-Durlacher JE, Treister NS, et al. Future Oncol. 9(12), 1883-92, (2013)

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Hypoxia-inducible factor 1 regulation through cross talk between mTOR and MT1-MMP. Sakamoto T, Weng JS, Hara T, et al. Mol. Cell. Biol. 34(1), 30-42, (2014)

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From The Cover: Bifurcation Of Insulin Signaling Pathway In Rat Liver: MTORC1 Required For Stimulation Of Lipogenesis, But Not Inhibition Of Gluconeogenesis Li, S., et al. Proc. Natl. Acad. Sci. U. S. A. 107, 3441-3446, (2010)

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Podocyte autophagic activity plays a protective role in renal injury and delays the progression of podocytopathies. Zeng C, Fan Y, Wu J, et al. J. Pathol. 234(2), 203-13, (2014)

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Autophagy inhibition by sustained overproduction of IL6 contributes to arsenic carcinogenesis. Qi Y, Zhang M, Li H, et al. Cancer Res. 74(14), 3740-52, (2014)

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Requirement of Mammalian target of rapamycin complex 1 downstream effectors in cued fear memory reconsolidation and its persistence. Huynh TN, Santini E, and Klann E J. Neurosci. 34(27), 9034-9, (2014)

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Evaluation of T and B lymphocyte function in clinical practice using a flow cytometry based proliferation assay. Marits P, Wikström AC, Popadic D, et al. Clin. Immunol. 153(2), 332-42, (2014)

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Sirolimus for non-progressive NF1-associated plexiform neurofibromas: an NF clinical trials consortium phase II study. Weiss B, Widemann BC, Wolters P, et al. Pediatr. Blood Cancer 61(6), 982-6, (2014)

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Combined treatment of tacrolimus and everolimus increases oxidative stress by pharmacological interactions. Piao SG, Lim SW, Doh KC, et al. Transplantation 98(1), 22-8, (2014)

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A phase I trial of everolimus in combination with 5-FU/LV, mFOLFOX6 and mFOLFOX6 plus panitumumab in patients with refractory solid tumors. McRee AJ, Davies JM, Sanoff HG, et al. Cancer Chemother. Pharmacol. 74(1), 117-23, (2014)

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Rapamycin protects against Aβ-induced synaptotoxicity by increasing presynaptic activity in hippocampal neurons. Ramírez AE, Pacheco CR, Aguayo LG, et al. Biochim. Biophys. Acta 1842(9), 1495-501, (2014)

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Pediatric patients with refractory central nervous system tumors: experiences of a clinical trial combining bevacizumab and temsirolimus. Piha-Paul SA, Shin SJ, Vats T, et al. Anticancer Res. 34(4), 1939-45, (2014)

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Deficiency of cardiac Acyl-CoA synthetase-1 induces diastolic dysfunction, but pathologic hypertrophy is reversed by rapamycin. Paul DS, Grevengoed TJ, Pascual F, et al. Biochim. Biophys. Acta 1841(6), 880-7, (2014)

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Activation of the MAPK11/12/13/14 (p38 MAPK) pathway regulates the transcription of autophagy genes in response to oxidative stress induced by a novel copper complex in HeLa cells. Zhong W, Zhu H, Sheng F, et al. Autophagy 10(7), 1285-300, (2014)

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eIF4E-Overexpression imparts perillyl alcohol and rapamycin-mediated regulation of telomerase reverse transcriptase. Sundin T, Peffley D, and Hentosh P Exp. Cell Res. 319(13), 2103-12, (2013)

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Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. André F, O'Regan R, Ozguroglu M, et al. Lancet Oncol. 15(6), 580-91, (2014)

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Targeting S1P1 receptor protects against murine immunological hepatic injury through myeloid-derived suppressor cells. Liu G, Bi Y, Wang R, et al. J. Immunol. 192(7), 3068-79, (2014)

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Methyllycaconitine alleviates amyloid-β peptides-induced cytotoxicity in SH-SY5Y cells. Zheng X, Xie Z, Zhu Z, et al. PLoS ONE 9(10), e111536, (2014)

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The role of mechanistic target of rapamycin (mTOR) complexes signaling in the immune responses. Soliman GA Nutrients 5(6), 2231-57, (2013)

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Elutax paclitaxel-eluting balloon followed by bare-metal stent compared with Xience V drug-eluting stent in the treatment of de novo coronary stenosis: a randomized trial. Liistro F, Porto I, Angioli P, et al. Am. Heart J. 166(5), 920-6, (2013)

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Short and long term in vivo effects of Cyclosporine A and Sirolimus on genes and proteins involved in lipid metabolism in Wistar rats. Lopes PC, Fuhrmann A, Sereno J, et al. Metabolism 63(5), 702-15, (2014)

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Biosynthesis And Expression Of VE-cadherin Is Regulated By The PI3K/mTOR Signaling Pathway. Bieri, M., et al. Mol. Immunol. 46, 866-72, (2009)

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Rheb and mammalian target of rapamycin in mitochondrial homoeostasis. Groenewoud MJ and Zwartkruis FJ Open Biol. 3(12), 130185, (2013)

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Diagnostic value of tolerance-related gene expression measured in the recipient alloantigen-reactive T cell fraction. Lim DG, Park YH, Kim SE, et al. Clin. Immunol. 148(2), 219-26, (2013)

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New strategies to overcome resistance to mammalian target of rapamycin inhibitors in breast cancer. Vicier C, Dieci MV, and Andre F Curr. Opin. Oncol. 25(6), 587-93, (2013)

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Novel targeting of phosphatidylinositol 3-kinase and mammalian target of rapamycin in renal cell carcinoma. Cho D Cancer J. 19(4), 311-5, (2013)

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The rationale of targeting mammalian target of rapamycin for ischemic stroke. Chong ZZ, Yao Q, and Li HH Cell. Signal. 25(7), 1598-607, (2013)

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A retrospective analysis of two different sequences of therapy lines for advanced kidney cancer. Paglino C, Procopio G, Sabbatini R, et al. Anticancer Res. 33(11), 4999-5004, (2013)

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Catalase expression in MCF-7 breast cancer cells is mainly controlled by PI3K/Akt/mTor signaling pathway. Glorieux C, Auquier J, Dejeans N, et al. Biochem. Pharmacol. 89(2), 217-23, (2014)

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Rechallenge with mTOR inhibitors in metastatic renal cell carcinoma patients who progressed on previous mTOR inhibitor therapy. Maj-Hes A, Medioni J, Scotte F, et al. Oncology 85(1), 8-13, (2013)

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Rapamycin: in vitro profile of a new immunosuppressive macrolide. Sehgal, S.N. and Bansback, C.C. Ann. N. Y. Acad. Sci. 685, 58-67, (1993)

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Third-generation zotarolimus-eluting and everolimus-eluting stents in all-comer patients requiring a percutaneous coronary intervention (DUTCH PEERS): a randomised, single-blind, multicentre, non-inferiority trial. von Birgelen C, Sen H, Lam MK, et al. Lancet 383(9915), 413-23, (2014)

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Loss of hydrophobic motif and activation loop phosphorylation is a consequence and not the mechanism of S6 kinase 1 inhibition by rapamycin. Beigh MA, Showkat M, Hussain MU, et al. J. Biol. Regul. Homeost. Agents 27(2), 399-408, (2013)

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Monitoring The Autophagy Pathway In Cancer. Dorsey, F.C., et al. Meth. Enzymol. 453, 251-71, (2009)

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Combined EGFR and autophagy modulation impairs cell migration and enhances radiosensitivity in human glioblastoma cells. Palumbo S, Tini P, Toscano M, et al. J. Cell Physiol. 229(11), 1863-73, (2014)

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Effects of rapamycin and tacrolimus on mature endothelial cells and endothelial progenitor cells. Macunluoglu B, Atakan A, Gökçe I, et al. J. Pak. Med. Assoc. 62(8), 822-5, (2012)

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Conversion of calcineurin inhibitors with mammalian target of rapamycin inhibitors after kidney transplant. Nikoueinejad H, Soleimani A, Mirshafiey A, et al. Exp. Clin. Transplant. 11(1), 12-6, (2013)

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Everolimus's influence on persistent acute rejection after experimental lung transplantation. Brunner E, Lehle K, Hirt SW, et al. Adv. Clin. Exp. Med. 22(3), 355-9, (2013)

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Early vascular healing with biodegradable polymer coated sirolimus-eluting coronary stent implantation: assessed by optical coherence tomography results at 4-month follow-up. Abhyankar A, Prajapati J, Reddy S, et al. Minerva Cardioangiol. 61(3), 313-22, (2013)

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Nonmyeloablative HLA-matched sibling allogeneic hematopoietic stem cell transplantation for severe sickle cell phenotype. Hsieh MM, Fitzhugh CD, Weitzel RP, et al. JAMA 312(1), 48-56, (2014)

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Inhibition of the mTORC pathway in the antiphospholipid syndrome. Canaud G, Bienaimé F, Tabarin F, et al. N. Engl. J. Med. 371(4), 303-12, (2014)

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BOLERO-3 results: pharmacological activity or pharmacokinetic effect?--authors' reply. André F and Gianni L Lancet Oncol. 15(8), e304-5, (2014)

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A retrospective study of patients with malignant PEComa receiving treatment with sirolimus or temsirolimus: the Royal Marsden Hospital experience. Benson C, Vitfell-Rasmussen J, Maruzzo M, et al. Anticancer Res. 34(7), 3663-8, (2014)

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The synergistic effect of rapamycin combined with 5-fluorouracil in BALB/cByJNarl mice bearing CT-26 tumor cells. Chao TH, Chang GR, Chen WY, et al. Anticancer Res. 34(7), 3329-35, (2014)

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Rapamycin inhibits pre-B acute lymphoblastic leukemia cells by downregulating DNA and RNA polymerases. Wang Z, Xu F, Yuan N, et al. Leuk. Res. 38(8), 940-7, (2014)

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Rapamycin represses myotube hypertrophy and preserves viability of C2C12 cells during myogenesis in vitro. Gao H, Ao M, Wang H, et al. Transplantation 98(2), 139-47, (2014)

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Malignant renal epithelioid angiomyolipoma with liver metastasis after resection: a case report with multimodality imaging and review of the literature. Vicens RA, Jensen CT, Korivi BR, et al. J. Comput. Assist. Tomogr. 38(4), 574-7, (2014)

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Analysis by optical coherence tomography of long-term arterial healing after implantation of different types of stents. Nakagawa M, Otake H, Shinke T, et al. Can. J. Cardiol. 30(8), 904-11, (2014)

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Analysis of rapamycin induced autophagy in Dictyostelium discoideum. Swer PB, Lohia R, and Saran S Indian J. Exp. Biol. 52(4), 295-304, (2014)

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Immunosuppressive compounds exhibit particular effects on functional properties of human anti-Aspergillus Th1 cells. Tramsen L, Schmidt S, Roeger F, et al. Infect. Immun. 82(6), 2649-56, (2014)

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Efficacy of everolimus in patients with advanced renal cell carcinoma refractory or intolerant to VEGFR-TKIs and safety compared with prior VEGFR-TKI treatment. Kato R, Obara W, Matsuura T, et al. Jpn. J. Clin. Oncol. 44(5), 479-85, (2014)

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Synergistic therapeutic vascular cytoprotection against complement-mediated injury induced via a PKCα-, AMPK-, and CREB-dependent pathway. Hamdulay SS, Wang B, Calay D, et al. J. Immunol. 192(9), 4316-27, (2014)

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Readmission rate after coronary artery bypass grafting versus percutaneous coronary intervention for unprotected left main coronary artery narrowing. Roh JH, Kim YH, Ahn JM, et al. Am. J. Cardiol. 113(10), 1639-46, (2014)

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PPARγ activation attenuates glucose intolerance induced by mTOR inhibition with rapamycin in rats. Festuccia WT, Blanchard PG, Belchior T, et al. Am. J. Physiol. Endocrinol. Metab. 306(9), E1046-54, (2014)

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Controversies in renal cell carcinoma: treatment choice after progression on vascular endothelial growth factor-targeted therapy. Calvo E, Grünwald V, and Bellmunt J Eur. J. Cancer 50(7), 1321-9, (2014)

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Therapy of mRCC beyond mTOR-inhibition in clinical practice: results of a retrospective analysis. Maute L, Grünwald V, Weikert S, et al. J. Cancer Res. Clin. Oncol. 140(5), 823-7, (2014)

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Rapamycin-resistant effector T-cell therapy. Fowler DH Immunol. Rev. 257(1), 210-25, (2014)

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Phase I study of neratinib in combination with temsirolimus in patients with human epidermal growth factor receptor 2-dependent and other solid tumors. Gandhi L, Bahleda R, Tolaney SM, et al. J. Clin. Oncol. 32(2), 68-75, (2014)

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Cholesterol esterification as a mediator of proliferation of vascular smooth muscle cells and peripheral blood mononuclear cells during atherogenesis. Mulas MF, Maxia A, Dessì S, et al. J. Vasc. Res. 51(1), 14-26, (2014)

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Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection. Chu LW, Huang YL, Lee JH, et al. J. Biomed. Opt. 19(1), 011018, (2014)

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A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC). Molina AM, Hutson TE, Larkin J, et al. Cancer Chemother. Pharmacol. 73(1), 181-9, (2014)

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