Topotecan shows modest clinical activity against cisplatin-refractory ovarian cancer, although the dose-intensity is compromised by the depth of the granulocyte nadir and the duration of granulocytopenia. Further studies of topotecan may necessitate a reevaluation of optimal dose schedule, with the possible incorporation of multilineage cytokines, and its activity in taxane-resistant tumors.
A genome-wide hypomethylation is a common and crucial event in cancer. This study was to evaluate common epithelial ovarian cancer (EOC) if long interspersed element-1 (LINE-1) repetitive sequences methylation levels are progressively decreased during multistage carcinogenesis and there are the correlation between LINE-1 methylation levels and clinicopathologic characteristics. A total of 59 pairs of microdissected EOC tissues obtained from patients with EOC were examined for the methylation levels of LINE-1 repetitive sequences by a COBRALINE-1 (combined bisulfite restriction analysis of LINE-1) PCR protocol. The methylation levels were correlated with clinicopathologic parameters to determine the potential role of global hypomethylation as a prognostic marker for EOC. The LINE-1 methylation levels of 59 EOCs, 34.87 +/- 7.39%, were lower than in representative normal ovarian tissues (46.89 +/- 8.31%; 95% CI: 9.42-14.62; P < 0.001, paired-two-tailed t test). A decrease in the LINE-1 level of methylation was correlated with histological subtypes, higher FIGO and advanced tumor grade. Patients with greater hypomethylation (i.e., a methylation level
A subset of patients with platinum-refractory disease that initially responded to a taxane and who eventually have a platinum-free interval of at least 1 year may respond to carboplatin reinduction. This finding may be secondary to paclitaxel or docetaxel therapy that leads to the reversal of platinum resistance, or the prolonged platinum-free interval permits the loss of resistance to platinum by the tumor. Carboplatin reinduction should be considered in the treatment of patients whose ovarian cancer progresses after an initial sensitivity to a taxane and who had a prolonged platinum-free interval.
Background: The aim of this study was to evaluate epigenetic status of cyclin A1 in human papillomavirusassociated cervical cancer. Y. Tokumaru et al., Cancer Res 64, 5982-7 (Sep 1, 2004)demonstrated in head and neck squamous-cell cancer an inverse correlation between cyclin A1 promoter hypermethylation and TP53 mutation. Human papillomavirus-associated cervical cancer, however, is deprived of TP53 function by a different mechanism. Therefore, it was of interest to investigate the epigenetic alterations during multistep cervical cancer development.
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