An investigation of the inflammatory response in patients with prostate cancer

McArdle, Peter Alexander (2006) An investigation of the inflammatory response in patients with prostate cancer. MD thesis, University of Glasgow.

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Abstract

Prostate cancer remains a major global health problem. Each year, in the UK, more than 27,000 patients are diagnosed with prostate cancer and approximately 9,500 die of their disease. The therapeutic options range from treatments primarily aimed at cure, such as radical surgery or radical radiotherapy, in patients with organ-confined disease to palliative treatments such as homrone therapy or chemotherapy used in patients with advanced disease. In chapter 1, the epidemiology, pathology, clinical features and treatment of prostate cancer are discussed. In chapter 2, the specific cellular and non-specific systemic inflammatory responses are discussed. In chapter three, the influence of tumour-bed lymphocyte infiltration on survival in patients with prostate cancer was evaluated. In chapter four, the effect of the systemic inflammatory response on outcome in patients with metastatic prostate cancer was investigated. In chapter five, the relationship between IL-6 and C-reactive protein in patients with untreated prostate cancer and benign prostatic disease was evaluated. Given that the inflammatory response appears to be important in predicting outcome in patients with prostate cancer, the question of whether C-reactive protein, could be used in the diagnostic setting to detect prostate cancer was explored in chapter 6. In conclusion, these studies suggest that in patients with prostate cancer, both the presence of a systemic inflammatory response and a profuse CD4+ lymphocyte infiltration of the tumour bed, predict poor survival. The negative impact of the systemic inflammatory response has been well documented in a variety of other common solid tumours. In contrast, the effect on survival of tumour bed lymphocyte infiltration appears to differ between tumour types. Whereas the presence of tumour-bed lymphocyte infiltration appears to be protective in patients with colorectal cancer, it appears to be detrimental in patients with prostate cancer. The reasons for these differences are as yet not clear. However, given that tumour lymphocyte infiltration parallels that of other inflammatory cells and that an elevated C-reactive protein is associated with poor survival in both tumour types, it may be that the source of interleukin-6 differs in different tumours. In colorectal cancer patients it has been reported that interleukin-6 concentrations increase with tumour stage and correlate with CEA concentrations. This would suggest that in colorectal cancer patients, interleukin-6 is produced by the tumour cells. In contrast, in patients with prostate cancer there is no significant correlation between serum interleukin-6 and PSA concentrations. It may therefore be that in patients with prostate cancer, interleukin-6 is produced by the host inflammatory cells rather than the tumour. If this were so, it might have implications for the treatment of the systemic inflammatory response in patients with different tumour types. (Abstract shortened by ProQuest.).

Item Type: Thesis (MD)
Qualification Level: Doctoral
Additional Information: Adviser: Donald McMillan
Keywords: Oncology, Immunology
Date of Award: 2006
Depositing User: Enlighten Team
Unique ID: glathesis:2006-71430
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 10 May 2019 10:49
Last Modified: 10 May 2019 10:49
URI: http://theses.gla.ac.uk/id/eprint/71430

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