Improving the outcome of patients with premalignant and malignant disorders of the vulva

[摘要] Research presented in this thesis was driven by the need to identify risk factors that predict local recurrence (LVR) in patients with vulval cancer (VSCC), and the need for more effective treatments for women with vulvar intraepithelial neoplasia (VIN). To identify the risk factors that predispose women to LVR, a multivariate analysis was performed on a well-characterized cohort of women treated for VSCC. This analysis revealed that the only independent predictor of LVR was the presence of Lichen Sclerosis (LS). These women were five times more likely to recur than those without LS. VIN is a recognised precursor lesion of HPV-positive VSCC. Topical application of Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, has been shown to be an effective treatment for genital warts; a condition caused by HPV. Although the mechanism(s) by which EGCG influences the growth of HPV-associated proliferative disorders are unknown, I demonstrate that EGCG inhibits cell proliferation and promotes apoptosis, an effect that was accompanied by down-regulation of the E6 and E7 proteins and the induction of p53, p21 and pRb. Biochemical analysis revealed that EGCG did not stimulate E6 degradation by enhancing poly-ubiquitination and proteasome-mediated degradation, suggesting that EGCG-mediated E6 proteolysis occurred through other mechanisms.

[发布机构] University:University of Birmingham;Department:Institute of Cancer and Genomic Sciences

[关键词] R Medicine;RG Gynecology and obstetrics