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The role of Heat shock protein in the process of cartinogeneis and progression of human ovarian cancer

Research Project

Project/Area Number 06671671
Research Category

Grant-in-Aid for General Scientific Research (C)

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

Principal Investigator

SAGAE Satoru  Sapporo Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (00187056)

Co-Investigator(Kenkyū-buntansha) KOIZUMI Motoiki  Sapporo Medical University, School of Medicine, clinical instructor, 医学部, 助手 (50244348)
SATO Noriyuki  Sapporo Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (50158937)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsovarian cancer / carcinogenesis / invasion and metastasis / heat shock protein / p53 gene product / Rb gene product / tumor antigen / host-immune response
Research Abstract

In the previous studies, we reported Rb or p53 geen products could be bind with intracellular heat shock proteins in ovarian cancer cell lines, with some corelation with carcinogenesis in human cells.
In this studywe performed a immunohistochemical analysis of heat shock proteinp53 or Rb gene products in human ovarian cancerwhich showed p53 protein expression was associated with cancer progression, but Rb products and their phosphorylating enzyme cdc-2 was expressed in the early process of carcinogenesis. Further, by using newly produced anti-hap 73 monoclonal antibody (Hybridoma 13 : 737,1994), hap73 expressions were examined with ovarian tisuues ; negative for normal ovarial tissues, 36% of bening tumors, 77% of borderline tumors, and 68% in early stage ovarian cancer, 65% in advanced ovarian cancer. And Rb proteins were also expressd in the similar fashion, at borderline tumors most frequently. But, the frequency of p53 expression was increased with the grade of malignancies during c … More arcinogenesis and progression. And as the prognostic factor, only p53 expression was associated with poor prognosis of ovarian cancer patients.
70kDa heat shock proteins overexpress in the process of carcinogenesis and may be expressed on the surface, as an important tumor-rejection antigen during hostimmune responses. We reported that one of the antigens expressed on the surface of H-ras transformed fibrosarcoma cell line, W31 from rat fetal fibroblast WFB was heat shock protein, especially hsc 73, and the cytotoxicity of CE3+4-8-T cell receptor alphabeta-killer (DNT) cells for W31 was recognized as the ligand of hsc73 with certain celluar nascent of mutant peptides from the tumor cell, and this immunologic reaction was also detected in the system of human ovarian cancer cell lines. Further analysis of these intracellular peptides were performed between rat fetal cells and W31 tumor cells, cytotoxicity included with peptides was inhibited with hsc73 antibody and proteinase treatment was blocked with this reaction. This means these peptides are very important in the immunoreaction of hsc73-ralated cytotoxicity in the process of tumor rejection. Less

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Tsuboi N, Sato N, Kikuchi K.: "Monoclonal antibody specifically reacting against 73-Kilodalton heat shock cognate protein:possible expression on mammalian cell surface." HYBRIDOMA. 13. 373-381 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takeda T, Sagae S, Kudo R et al: "Multiple primary malignancies in patients with gynecologic cancer." Int J Gynecol Cancer. 5. 34-39 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kobayashi K, Sagae S, et al: "Microsatellite instability in endometrial carcinomas;frequent replication errors in tumors of early onset and/or with poorly differentiated histology" Genes Chromosomes & Cancer. 14. 128-132 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kobayashi K, Sagae S, et al: "Mutation analysis of mismatch repair genes, hMLH1 and hMSH2, in sporadic endometrial and ovarian 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
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takashima S, Sato N, Sagae S, Kudo R, Kikuchi K.: "Interaction between cell-surface-expressed 70kDa heat shock protein-like antigen and CD3+4-8-killer T cells." Transplantation Proceedings. (in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takashima S, Sato N, Sagae S, et al: "Involvement of peptide antigens in the cytotoxicity between 70kDa heat shock cognate protein-like molecule and CD3^+,CD4^-,CD8^-,T cell receptor α/β^-killer T cells" J Immunol. (in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sagae S. ed.: "Prognostic factors in Ovarian Cancer" Kokuku Print.Sappro, Japan, 80 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tsuboi N,Sato N,Kikuchi K.: "Monoclonal antibody specifically reacting against 73-Kilodalton heat shock cognate protein : possible expression on mammalian cell surface." HYBRIDOMA. 13. 373-381 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takeda T,Sagae S,Kudo R et al: "Multiple primary malignancies in patients with gynecologic cancer." Int J Gynecol Cacner. 5. 34-39 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kobayashi K,Sagae S,et al: "Microsatellite instability in endometrial carcinomas ; frequent replacation errors in tumors of early onset and/or with poorly differentiated histology" Genes Chromosomes & Cancer. 14. 128-132 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kobayashi K,Sagae S,et al: "Mutation analysis of mismatch repair genes, hMLH1 and hMSH2, in sporadic endometrial and ovarian 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
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takashima S,Sato N,Sagae S,Kudo R,Kikuchi K.: "Interaction between cell-surface-expressed 70kDa heat shock protein-like antigen and CD3+4-8-killer T cells." Transplantation Proceedings. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takashima S,Sato N,Sagae S,et al: "Involvement of peptide antigens in the cytotoxicity between 70 kDa heat shock cognate protein-like molecule and CD3^+, CD4^-, CD8^-, T cell receptor alpha/beta-killer T cells" J Immunol. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sagae S,ed.: Prognostic factors in Ovarian Cancer. Hokuku Print, 80 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nihei T,: "Demonstration of selective protein complexes of p53 with 73kDa heat shock cognate protein,but not with 72kDa heat shock protein in human tumor cells." Cancer Letters. 73. 181-189 (1993)

    • Related Report
      1995 Annual Research Report
  • [Publications] Saito H,: "Detailed deletion mapping of chromosome 17q in ovarian and breast cancers:2-cM region on 17q21.3 often and commonly deleted in tumors." Cancer Res.53. 3382-3385 (1993)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tamura Y,: "70kDa heat shock cognate protein is a transformation-associated antigen,and a possible target for the host's anti-tumor immunity." J Immunol. 151. 5516-5524 (1993)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tsuboi N: "Monoclonal antibody specifically reacting against 73-Kilodalton heat shock cognate protein:possible expression on mammalian cell surface." HYBRIDOMA. 13. 373-381 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kobayashi K,: "Microsatellite instability in endometrial carcinomas;frequent replication errora in tumors of early onset and/or with poorly differentiated histology." Genes Chromosomes & Cancer. 14. 128-132 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kobayashi K,: "Mutation analysis of mismatch repair genes,hMLH1 and hMSH2,in sporadic endometrial and ovarian carcinomas with microsatellite instability." Jpn J Cancer Res in press. (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takeda T,: "Multiple primary malignancies in patients with gynecologic cancer." Int J Gynecol Cancer.5. 34-39 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takashima S: "Involvement of peptide antigens in the cytotoxicity between 70kDa heat shock cognate protein-like molecule and CD3^+,CD4^-,CD8^-,T cell receptor d/β-killer T cells" J.Immunol,. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sagae S,: "Prognostic factors in Ovarian Cancer" Kokoku Print.Sapporo,Japan, 80 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 武田智幸、寒河江悟、他: "ヒト卵巣癌の進行におけるp53,Rb蛋白とheat shock protein 70 familyの発現" 日本産科婦人科学会講演要旨集. 46(Supplement). 169- (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 杉村政樹、寒河江悟、他: "ヒト卵巣癌における70kDa熱ショック蛋白(hsp)ファミリーの発現" 日本婦人科病理コルポスコピー学会講演要旨集. 12. 37- (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 武田智幸、寒河江悟、他: "ヒト上皮性卵巣癌におけるRb蛋白、cdc2,hsp70 familyの免疫組織化学的検討" 日本癌学会講演要旨集. 1349- (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 斉藤 督、寒河江悟、他: "卵巣癌における第6染色体長腕の共通欠失領域から単離された癌抑制遺伝子の候補遺伝子の解析" 日本癌学会講演要旨集. 724- (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 高嶋 知、寒河江悟、佐藤昇志: "腫瘍抗原としての熱ショック蛋白質(hsp)の宿主免疫応答" 日本産科婦人科学会講演要旨集. 47(Supplement). 141- (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Terasawa K,Sagae S,et al.: "Heat shock protein(hsp) 70 family in the carcinogenesis of ovarian cancer" proceeding of American Association of Cancer Research. 36. 1176- (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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