Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/71554
DC FieldValueLanguage
dc.contributor.authorWu, M.J.en_US
dc.contributor.authorChang, C.H.en_US
dc.contributor.authorChiu, Y.T.en_US
dc.contributor.authorWen, M.C.en_US
dc.contributor.authorShu, K.H.en_US
dc.contributor.authorLi, J.R.en_US
dc.contributor.authorChiu, K.Y.en_US
dc.contributor.authorChen, Y.T.en_US
dc.date2012zh_TW
dc.date.accessioned2014-06-11T06:01:55Z-
dc.date.available2014-06-11T06:01:55Z-
dc.identifier.issn1078-1439zh_TW
dc.identifier.urihttp://hdl.handle.net/11455/71554-
dc.description.abstractObjective: We previously reported a very high cumulative incidence of urothelial carcinoma in Taiwanese kidney transplant recipients. Rapamycin, the inhibitor of mTOR Complex I, provides alternative immunosuppressive therapy after kidney transplantation with less neoplastic potential. We examined the in vivo and in vitro effects of rapamycin on urothelial carcinoma. Materials and methods: The rat model of urothelial carcinoma was induced by 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in Fischer F344 rats. The anti-tumor effect of rapamycin was assessed grossly, microscopically, and by Western blot analysis. The mechanism of rapamycin's attenuation of urothelial carcinoma was also evaluated by T24 cells. Results: Rapamycin significantly reduced urinary bladder tumor growth in the rat model of 0.05% BBN-induced urothelial carcinoma (P < 0.001). The blood trough levels of rapamycin were correlated with the occurrence of urothelial carcinoma. In vitro, rapamycin also inhibited the cell proliferation, migration, and invasion, as well as the protein expression of vascular endothelial growth factor-A of T24 urothelial carcinoma cells, whereas rapamycin did not induce significant apoptosis in T24 cells. Rapamycin decreased the expression of phospho-mTOR, phospho-S6K, cyclin D1, and VEGF-A. Rapamycin also activated AKT in T24 cells in the rat model of urothelial carcinoma. The rapamycin-associated activation of AKT was inhibited by rictor siRNA, but not raptor siRNA. Conclusions: This study provides in vitro and in vivo evidence that rapamycin may inhibit the development of urothelial carcinoma. The present findings also suggest rictor-dependent AKT activation as a consequence of mTORC I inhibition. (C) 2012 Elsevier Inc. All rights reserved.en_US
dc.language.isoen_USzh_TW
dc.relationUrologic Oncology-Seminars and Original Investigationsen_US
dc.relation.ispartofseriesUrologic Oncology-Seminars and Original Investigations, Volume 30, Issue 1, Page(s) 69-77.en_US
dc.relation.urihttp://dx.doi.org/10.1016/j.urolonc.2009.11.009en_US
dc.subjectAKTen_US
dc.subjectRapamycinen_US
dc.subjectRictoren_US
dc.subjectUrothelial carcinomaen_US
dc.subjectVEGFen_US
dc.subjectde-novo malignanciesen_US
dc.subjectmammalian targeten_US
dc.subjectkidney-transplantationen_US
dc.subjectrenal-transplantationen_US
dc.subjectcell carcinomaen_US
dc.subjectgrowth-factoren_US
dc.subjectcanceren_US
dc.subjectmtoren_US
dc.subjectefficacyen_US
dc.subjectimmunosuppressionen_US
dc.titleRictor-dependent AKT activation and inhibition of urothelial carcinoma by rapamycinen_US
dc.typeJournal Articlezh_TW
dc.identifier.doi10.1016/j.urolonc.2009.11.009zh_TW
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypeJournal Article-
item.cerifentitytypePublications-
item.fulltextno fulltext-
item.languageiso639-1en_US-
item.grantfulltextnone-
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