U196147.pdf (13.64 MB)
Radiosensitivity in bladder cancer cells
thesisposted on 2014-12-15, 10:34 authored by Benedict T. Sherwood
Potentially curative treatment options for patients with organ-confined transitional cell carcinoma (TCC) of the bladder (T1-4a/N0/M0) are radical cystectomy or radiotherapy (RT)-based 'bladder-preserving' regimens. A substantial number of patients who receive RT fail to respond (approximately 50%). Consequently, a greater understanding of the mechanisms of radioresistence is required, together with predictive information regarding the response of tumours to RT. Hypoxia and intrinsic cellular Radiosensitivity (IRS) are examined here, a factors that may influence the outcome of RT.;An immunohistochemical assay using hypoxia-related carbonic anhydrase IX (CA IX) was undertaken to determine the prognostic significance of hypoxia in bladder tumours treated with RT. A modified version of the alkaline comet assay (ACA) was used to examine differences in IRS between cells derived from TCC specimens. Nuclear factors that influence comet formation (and therefore radiosensitivity) were also examined, such as DNA double strand break (DSB) rates and differences in nuclear matrix protein (NMP) composition.;CA IX immunostaining did not provide prognostic information with respect to response to radical RT. ACA analysis indicated a wide range of responses between tumours. In TCC cell lines, DSB rates are not demonstrably different in cells of differentiated radiosensitivity, however, comparative analysis of nuclear proteins identified differences in their constitutive NMPs and repair enzymes.;These results do not provide evidence that hypoxia influences outcome after RT, but support the contention that ICR is important in dictating the response of bladder tumours to RT. Furthermore, in bladder cancer cell lines of differing radiosensitivity, differences in NMP and repair enzymes are identified. Further work is required to determine whether these are of prognostic importance.
Date of award2005-01-01
Author affiliationCancer Studies and Molecular Medicine
Awarding institutionUniversity of Leicester