Mehmood, RK;
(2007)
In vitro assessment of cisplatin and oxaliplatin in oesophageal cancer.
Doctoral thesis , UCL (University College London).
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Abstract
Oesophageal carcinoma is a common and highly virulent malignancy. Systemic metastatic disease is present in 50% of patients at diagnosis and will develop in the vast majority of the rest. Combined chemotherapy and radiotherapy is the standard regime of care in the non-surgical management of oesophageal cancer. Preoperative chemoradiotherapy followed by surgery continues to be actively studied in the surgical management of locally advanced oesophageal cancer. The limited efficacy and substantial toxicity of conventional 5-FU-cisplatin-based chemotherapy combined with radiation, has prompted the evaluation of newer agents, including the oxaliplatin, taxanes and irinotecan. Oxaliplatin has demonstrated antitumor activity against cisplatin resistant colon cancer both in vitro and in vivo and is now used in the chemotherapeutic treatment of metastatic colon and rectal cancer. Despite extensive study the precise mechanisms of action of oxaliplatin are yet to be fully elucidated. Much of the knowledge is based on the extrapolation of the findings for cisplatin and other 1,2 diaminocyclohexane ligand (DACH) compounds. Like cisplatin, oxaliplatin reacts with DNA and forms DNA adducts at the same sites as cisplatin. However, oxaliplatin is markedly less reactive with DNA and forms fewer adducts with DNA than equimolar cisplatin. Both react with cellular proteins a possibly significant mechanism of their toxicity. This thesis compares the cytotoxicity and pharmacology of oxaliplatin and cisplatin on two oesophageal cancer cell lines in vitro. Gene expression studies were performed to determine the predictive value of Excision Repair Cross Complementing 1(ERCC1), a DNA repair enzyme, as a potential marker of chemotherapeutic response or resistance of cisplatin and oxaliplatin in oesophageal adenocarcinoma cells.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | In vitro assessment of cisplatin and oxaliplatin in oesophageal cancer |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. Third party copyright material has been removed from the ethesis. Images identifying individuals have been redacted or partially redacted to protect their identity. |
| UCL classification: | |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1569252 |
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