Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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Master Thesis The Involvement of Ceramide Metabolizing Genes and Their Products in Docetaxel Induced Apoptosis in Human Prostate Cancer Cells(Izmir Institute of Technology, 2009) Başsoy, Esen Yonca; Baran, YusufPatients diagnosed with prostate cancer initially respond to androgen ablation therapy with tumor cells undergoing apoptosis, but then the patients relapse in time and develop metastatic, androgen independent prostate cancer. Docetaxel has been widely used for treatment of patients with advanced metastatic prostate cancer. The sphingolipid, ceramide, is a lipid second messenger that mediates a lot of functions as regulation of cell growth, proliferation, differentiation, senescence and apoptotic responses in various cancer cells. The enzyme, glucosylceramide synthase (GCS) is responsible for bioactivation of the proapoptotic mediator ceramide to antiapoptotic glucosylceramide. Likewise, sphingosine kinase-1 (SK-1) transforms apoptotic ceramide to antiapoptotic sphingosine 1-phosphate. Emerging results indicate that GCS and SK-1 are overexpressed in resistant cancer cell lines and cancerous tissue samples of patients. Moreover apoptosis and inhibition of cell proliferation and survival are induced by intracellular ceramide levels including enhancement in de novo ceramide production, exogenous delivery of cell permeable ceramide and inhibition of ceramide metabolism by affecting GCS and SK-1. In this study, we applied exogenous ceramide and inhibitors of GCS and SK-1 in combination with docetaxel for sensitizing androgen independent prostate cancer cells to chemotherapy and provide their effectively utilization with minimizing side effects of the drugs. The de novo generation of ceramide is regulated by the genes (LASS1-6) in mammalian cells. Therefore in this study, we examined the possible roles of the ceramide/S1P and ceramide/GS by examining expression levels of GCS, SK-1 and LASS1,2,4,5,6 which can play important roles to overcome androgen independent.Master Thesis Investigating the Role of Zoledronic Acid on Interleukin-6 Cytokine Expression in Prostate Cancer Cell Lines(Izmir Institute of Technology, 2006) Abbasi Asbagh, Layka; Doymaz, FuatProstate cancer (CaP) is a common disease in aged men. Androgen deprivation therapy is the first line treatment for advanced disease. Following this therapy, within few months CaP cells become androgen independent in a few mounths. The mechanism responsible for development of androgen-independent cancer is not known. Evidences suggest that growth factors and cytokines including Interleukin.6 (IL-6) cast a main role in this mechanism. IL.6 is an important cytokine on CaP progression. Bisphosphonates inhibit the proliferation and induce the apoptosis of certain prostate cancer cell lines, in vitro. However, their mechanism of action is not clearly understood. One possible mechanism might be the IL-6 mediated pathway. This relation between zoledronic acid (ZA) and IL-6 hasn.t been studied.The objective of this study is to evaluate the cytotoxic and apoptotic effect of ZA on hormone independent CaP cell line (PC-3) and to understand the relation of underlying mechanism of ZA-mediated cytotoxicity and IL-6 expression. PC-3 cells were treated with different concentrations of ZA. Drug-mediated cytotoxicity and apoptosis were determined. IL-6 levels were measured from the supernatants of PC-3 cells at 24, 48, 72 hrs.Maximum cytotoxicity was achieved at 90 and 100 .M of ZA. ZA produced the classical DNA ladders on gel synonymous of apoptosis. The decrease in IL-6 secretion was found to be statistically significant compared to controls. The decreasing effect of ZA on IL-6 expression might suggest a new mechanism of action of ZA's antitumor activity. This outcome may offer a novel therapy that utilizes IL-6 antagonists along with ZA in CaP patients.