二瓶 岳人 札幌医科大学, 医学部, 助手 (30274939)
KUDO Ryuichi Sapporo Med.Uni.OB/GYN Professor, 医学部, 教授 (70045409)
NISHIKAWA Akira Sapporo Med.Uni.OB/GYN Clin.Instruct., 医学部, 助手 (70295351)
KOIZUMI Motoiki Sapporo Med.Uni.OB/GYN Clin.Instruct., 医学部, 助手 (50244348)
|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1997 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1996 : ¥1,300,000 (Direct Cost : ¥1,300,000)
In the current study, we reported that the frequency of replication error (RER) in endometrial cancer was significantly higher than that of ovarian cancer and two somatic mutations of hMLH1 were detected in a single endometrial cancer and RER was important in the carcinogenesis and progression of endometrial cancer, with poorer survival of the patients with RER(+) tumor.
Concerning to ovarian cancer, we reported the protein interaction of tumor suppressor gene products. such as p53 or Rb with 73 kDa heat shock cognate protein in ovarian cancer cell lines. In tumor immunology, cellular surface antigens were associated with HSP in the carcinogenesis of ovarian cancer cells and the importance of HSP was reported at the rejection in the organ transplantation and as CTL-targeted tumor rejection antigens. In human ovarian cancer, we performed an analysis of the association between hsc73 and p53 or Rb gene products. p53 was an independent prognostic factor, and even in the p53 negative cases,
hsc73 overexpression and reduced pRB expression were also important as the prognostic factor. Furthermore, we detected a commonly deleted region in ovarian cancers to a 300-kb segment of chromosome 6q27 containing the putative tumor suppressor gene.
Under the analysis of telomerase activity in human ovarian tumor, the level of its activities was increased from benign, LMP,and malignant tumors, but not associated with clinical prognostic factors. From the analysis with cell cycle-regulated protein, we found that degeneration of cell cycle regulatory proteins upregulated telomerase activity in human ovarian cancer.This is a first report of the interaction between telomerase activity and cell cycle-regulated protein in human tumor.
About the chemosensitivity of ovarian cancer cells, we analyzed the association of apoptosis during Taxol or CDDP containing chemotherapy. From the quantitation of DNA fragmentation during these drug-induced apoptosis, apoptosis was required with more than constant level of drug stimuli and DNA fragmentation varied in the different cell lines. From the experiments of IL-6 administration, CDDP-induced apoptosis was prevented with high doses of IL-6. Less