Rapamycin: Current clinical uses and major adverse effects

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dc.contributor.advisorPórszász, Róbert
dc.contributor.advisordeptDebreceni Egyetem::Általános Orvostudományi Kar::Farmakológiai és Farmakoterápiai Intézethu_HU
dc.contributor.authorYan, Chen
dc.contributor.departmentDE--Általános Orvostudományi Karhu_HU
dc.contributor.opponentDrimba, László
dc.contributor.opponentSzentmiklósi, József András
dc.contributor.opponentdeptKenézy Kórház Aneszteziológiai és Intenziv Therápiás Osztályhu_HU
dc.contributor.opponentdeptDebreceni Egyetem::Általános Orvostudományi Kar::Farmakológiai és Farmakoterápiai Intézethu_HU
dc.date.accessioned2015-11-20T11:41:58Z
dc.date.available2015-11-20T11:41:58Z
dc.date.created2015-08-27
dc.description.abstractRapamycin (Sirolimus) is a mTOR inhibitor. The mTOR pathway is a central regulator of cell growth and metabolism in response to hormonal and environmental stimuli. There are two functionally unique multi-protein enzymatic complexes that contain mTOR. mTORC1 which is sensitive to rapamycin, and mTORC2, which is practically insensitive to rapamycin. The mTORC1 pathway summarize information from both intracellular and extracellular stimuli such as energy level, growth factors, oxygen level, stress and amino acids to induce anabolic processes – protein synthesis, ribosome biogenesis, transcription, lipogenesis, energy metabolism - and inhibit catabolic processes such as autophagy and lyposome biogenesis to promote cell growth and proliferation through S6K1 and 4EBP1. mTORC2 pathway is insensitive to most stimuli, and can only be activated by growth factors and it controls cytoskeletal organization and cell survival and cell metabolism. Rapamycin was accepted by the FDA for preventing renal transplant rejection in 1997, because of its immunosuppressive characteristics, and for use in coronary-artery eluting stents in 2003 because of its antiproliferative property on vascular smooth muscle cells. Besides its use in kidney transplantation and coronary stent coating, rapamycin and its analogs have been proven their valuable uses in heart transplantation and several cancer types, such as metastatic advanced renal cell carcinoma, subependymal giant-cell astrocytoma, advanced pancreatic neuroendocrine tumors and advanced hormone receptor-positive breast cancer. However, despite the impressive features of rapamycin as an immunosuppressive, antiproliferative and antimigratory therapeutic agent, it does have numerous side effects, such as hyperlipidaemia, myelosuppression, nephrotoxicity, impaired wound healing and interstitial pneumonia, mainly due to the mTOR-S6K1 pathway which is common to multiple cell lines. In my thesis, I reviewed a series of landmark studies, regarding the mechanism of action and the clinical development of rapamycinhu_HU
dc.description.correctorLB
dc.description.courseáltalános orvostudományihu_HU
dc.description.courseactnappalihu_HU
dc.description.courselangmagyarhu_HU
dc.description.degreeegységes, osztatlanhu_HU
dc.format.extent42hu_HU
dc.identifier.urihttp://hdl.handle.net/2437/218723
dc.language.isoenhu_HU
dc.rightsNevezd meg! - Ne változtasd! 2.5 Magyarország*
dc.rights.urihttp://creativecommons.org/licenses/by-nd/2.5/hu/*
dc.subjectRapamycinhu_HU
dc.subjectmTORhu_HU
dc.subjectSirolimushu_HU
dc.subject.dspaceDEENK Témalista::Orvostudományhu_HU
dc.titleRapamycin: Current clinical uses and major adverse effectshu_HU
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Hallgatói dolgozatok (Általános Orvostudományi Kar)