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    The mammalian target of rapamycin protein expression in human granulosa cell tumors
    (GALENOS YAYINCILIK, 2019-01-01) Guralp, Onur; Bese, Tugan; Bildik, Gamze; Demikiran, Fuat; Ince, Umit; Malik, Eduard; Arvas, Macit; Oktem, Ozgur
    Objective: To investigate the role of mammalian target of rapamycin (mTOR) in human granulosa cell ovarian tumors and the therapeutic effect of rapamycin in COV434 mitotic granulosa cell lines. Material and Methods: A retrospective evaluation of the medical records and pathologic sections of patients with granulosa cell ovarian carcinoma was performed. mTOR and p-mTOR expression was immunohistochemically investigated. A COV434 cell culture were treated with 0.5, 1, 2, and 5 mu M rapamycin. Real-time growth curve analysis via xCELLigence system and apoptotic cell analysis via YO-PROT-1 Iodide were performed to assess the therapeutic effect of rapamycin on cancer cells. Results: A total of twenty patients were evaluated. mTOR staining was detected in 18 (90\%) patients. Mild, moderate, intense, and very intense staining was observed in three (15\%), eight (40\%), six (30\%), and one (5\%) sample, respectively. The mean mTOR staining ratio was 59 +/- 41\%. P-mTOR staining was observed in two ( 10\%) patients. One (5\%) patient had 5\% staining, and one (5\%) patient had 100\% staining for p-mTOR. Both of the latter patients had very intense staining. Rapamycin caused a dose-dependent growth arrest and induced apoptosis in COV434 mitotic granulosa cells. The real-time growth curves of the cells treated with these drugs were distinguished by a marked reduced slope after exposure for several hours, indicating a rapid onset of apoptosis. Live/dead cell analysis with YO-PRO-1 staining showed that rapamycin induced apoptosis in 24\% of the cells when used at 1 mu M concentration, whereas the rate increased to 61\% and 72\% when the cells were treated with 2 mu M and 5 mu M rapamycin, respectively. Conclusion: mTOR expression is observed in various degrees in 90\%, and p-mTOR expression is observed in only 10\% of patients with granulosa cell ovarian carcinoma. Rapamycin caused a dose-dependent growth arrest and apoptosis in COV434 mitotic granulosa cells.
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    Survival by self-destruction: A role for autophagy in the placenta?
    (W B SAUNDERS CO LTD, 2012-01-01) Bildirici, I.; Longtine, M. S.; Chen, B.; Nelson, D. M.
    Autophagy is a burgeoning area of research from yeast to humans. Although previously described as a death pathway, autophagy is now considered an important survival phenomenon in response to environmental stressors to which most organs are exposed. Despite an ever expanding literature in non-placental cells, studies of autophagy in the placenta are lagging. We review the regulation of autophagy, summarize available placental studies of autophagy, and highlight potential areas for future research. We believe that such studies will yield novel insights into how placentas protect the survival of the species by ``self-eating{''}. (C) 2012 Elsevier Ltd. All rights reserved.