Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/37449
Title: CHARACTERIZING CISPLATIN-RESISTANT NSCLC CELLS AND IDENTIFYING TRAIL AS A POTENTIAL SECOND-LINE THERAPY IN REFRACTORY CANCER CELLS
Authors: SEAH BEE KEE SERENA
Keywords: NSCLC, Cisplatin-resistance, TRAIL, Apoptosis
Issue Date: 28-Sep-2012
Source: SEAH BEE KEE SERENA (2012-09-28). CHARACTERIZING CISPLATIN-RESISTANT NSCLC CELLS AND IDENTIFYING TRAIL AS A POTENTIAL SECOND-LINE THERAPY IN REFRACTORY CANCER CELLS. ScholarBank@NUS Repository.
Abstract: Chemoresistance remains one of the greatest challenge in the clinical management for cancer. Despite initial response to chemotherapy, most cancer often relapse with a drug resistant phenotype. Thus, this study aims to characterize the molecular mechanisms underlying cisplatin resistance and thus design better chemotherapeutic strategies to combat the problem of resistance. In this regard, we develop a NSCLC cisplatin-resistant model to emulate the refractory disease condition. In this model, we found alterations in the energy metabolism and mitochondrial function of the cisplatin-resistant cells and proposed that mitochondrial dysfunction could contribute to the acquisition of resistance to cisplatin. In addition, we found that TRAIL can effectively induce apoptosis in the cisplatin-resistant cells, as a result of the redistribution of TRAIL receptors into the lipid rafts on the plasma membrane. Furthermore, we discovered that TRAIL was able to induce caspase-dependent intracellular peroxynitrite production, which function as an important mediator of cell death, in the cisplatin-resistant cells. Finally, our study also provides evidence for TRAIL to be used as a second-line treatment, either as a monotherapy or combination therapy, for refractory NSCLC and possibly other cisplatin-resistant models.
URI: http://scholarbank.nus.edu.sg/handle/10635/37449
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