Cholangiocarcinoma cell lines: proteomic analysis and enhancing response to chemotherapy.
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Cholangiocarcinoma (CCA) is a rare cancer with a poor prognosis. Much of medical research has focused on investigating cancers with a higher incidence and little focus has been devoted to this disease. The aim of this thesis was to perform a protein analysis of CCA and cholangiocyte cell lines. Differences between immortalised cancer and normal cells were sought in order to identify potential therapeutic targets and/or diagnostic tools. A variety of CCA cell lines were used, reflecting both intra and extrahepatic disease. The different subtypes of CCA through the developed and developing world are also represented so differences were also sought between them. Proteomic analysis was performed using DIGE with subsequent spot selection. Identified spots were extracted and processed using mass spectrometry. In addition, available chemotherapy agents were tested in vitro against the same cell lines to check for their action and how this could be enhanced. A benzodiazepine receptor antagonist (PK11195) was used to demonstrate apoptosis promotion in the presence of established cytotoxic agents (gemcitabine, etoposide, 5 fluorouracil and cisplatin). Cytotoxic assays were carried out using the SRB (Sulphorhodamine B) assay. Cell lines were tested for benzodiazepine receptor status using qRTPCR and response was correlated
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