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1997 Fiscal Year Final Research Report Summary

Analysis of genetic abnormalities in gynecologic malignancies, especially endometrial cancer and ovarian cancer

Research Project

Project/Area Number 08671910
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionSAPPORO MEDICAL UNIVERSITY

Principal Investigator

SAGAE Satoru  Sapporo Med.Uni.OB/GYN Assist.Prof., 医学部, 講師 (00187056)

Co-Investigator(Kenkyū-buntansha) 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)
Project Period (FY) 1996 – 1997
Keywordsendometrial cancer / ovarian cancer / genetic abnormalities / DNA repair gene / heat shock protein / p53 gene / Rb gene / telomerase
Research Abstract

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, … More 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

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Kobayashi K, Sagae S: "Mutational analysis of Mismatch repair genes,hMLH1 and hMSH2,in sporadic endometrial carcinomas with microsatellite instability." Jpn J Cancer Res. 87. 141-145 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takashima S, Sagae S: "Involvement of peptide antigens in the cytotoxicity between 70-kDa heat shock cognate protein-like molecule and CD3+,CD4-,CD8- TCR-α β-kille T cells." J Immunol. 157. 3391-3395 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Saito S, Sagae S: "Definition of a commonly deleted region in ovarian cancers to a 300-kb segment of chromosome 6q27." Cancer Res. 56. 5586-5589 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeda T, Sagae S: "Expression of heat shock protein(hsc73)in epithelial ovarian tumors and its clinical implications." Cancer. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Terasawa K, Sagae S: "Telomerase activity and cell cycle-associated proteins in human ovarian tumors" Clin Cancer Res. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishioka S, Sagae S: "Effects of interleukin-6(IL-6)on chemotherapy-induced apoptosis in human ovarian cancer cell lines." Jpn J Cancer Res. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 工藤 隆一、寒河 江悟: "「病理と臨床」別冊「腫瘍鑑別診断アトラス 子宮体部 第2版」" 文光堂(印刷中),

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kobayasshi K,Sagae S: "Mutational analysis of Mismatch repair genes, hMLH1 and hMSH2, in sporadic endometrial carcinomas with microsatellite instability" Jpn J Cancer Res. 87. 141-145 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takashima S,Sagae S: "Involvement of peptide antigens in the cytotoxicity between 70-kDa heat shock cognate protein-like molecule and CD3+, CD4-, CD8-, TCR-alphabeta-killer T cells." J Immunol. 157. 3391-3395 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saito S,Sagae S: "Definition of a commonly deleted region in ovarian cancers to a 300-kb segment of chromosome 6q27." Cancer Res. 56. 5586-5589 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeda T,Sagae S: "Expression of heat shock protein (hsc73) in epithelial ovarian tumors and its clinical implications." Cancer. in press. (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Terasawa K,Sagae S: "Telomerase activity and cell cycle-associated proteins in human ovarian tumors" Clin Cancer Res. in press.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishioka S,Sagae S: "Effects of interleukin-6(IL-6) on demotherary- induced apoptosis in human ovarian cancer cell lines." Jpn J Cancer Res. in press.

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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