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Biochemical Modulation targetting topoesomerase I and II

Research Project

Project/Area Number 03670588
Research Category

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

Allocation TypeSingle-year Grants
Research Field General surgery
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

HIRABAYASHI Naoki  Hiroshima Univ.Med.Hosp.Assistant Prof., 医学部・附属病院, 講師 (40221519)

Co-Investigator(Kenkyū-buntansha) AOGI Kenjiro  Hiroshima Univ.Med.Hosp.Resident, 医学部・附属病院, 医員
YOSHIDA Kazuhiro  Res.Inst.Nucl.Med.Biol.Dept.Surg., Research Associate, 原爆放射能医学研究所, 助手 (50230727)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1992: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1991: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsTopoisomerase I / Topoisomerase II / CPT-11 / Adriamycin / Apoptosis / トポイソメレースI / トポイソメレースII / バイオケミカルモジュレイション / トポイソメレ-スI / トポイソメレ-スII
Research Abstract

The following results were obtained during the research period.
1 The level of mRNA of topoisomerase I and II were found to be higher in digestive tract cancer tissues than those in adjacent normal tissues.
2 The positive correlation was obtained between the level of mRNA of topoisomerase II in breast cancer tissues and clinical response to adriamycin. In addition, the similar results were observed using nude mice transplantable xenograft tumor system.
3 The sequential treatment of CPT-11 followed by adriamycin exhibited synergistic effect against tumor xenograft tumors grown in nude mice, whereas simultaneous treatment of CPT-11 with adriamycin showed no synergistic effect.
4 The mRNA expression of topoisomerase II in xenograft tumors treated with CPT-11 reached the maximum 24-48 hr after treatment.
5 CPT-11 could induce apoptosis in colon cancer cell lines including WiDr, Colo 320 DM, and Colo201. The more P53 protein was in these cell lines, the higher incidence of apoptosis occured.
6 From the point of induction of apoptosis, the optimal concentration existed in terms of the induction of apoptosis inn colon cancer cell lines treated with CPT-11 and adriamycin.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Kim.R.: "Expression of MDR-1,GST-π,and topoisomerase II as an indicator of Clinical response of adriamycin." Anticancer Research. 11. 429-432 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kim.R.: "Clinical significance of P-glycoprotein expression analyzed by immunohistochemical staining in cancer tissues." The Japanese Journal of Surgery. 21. 590-593 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kim.R.: "mRNA expression of topoisomerase II in human tumors and nomal tissues." The Japanese Journal of Surgery. 21. 587-589 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 峠 哲哉: "抗癌剤感受性試験の現況とその問題点" 日本臨床外科医学会雑誌. 53. 751-757 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kim.R.: "Factors contributing to adriamycin sensitivity in human xenograft tumors:the relationship between expression of MDR-1,GST-π,and topoisomerase II genes and tumor sensitivity to adriamycin" Anticancer Research. 12. 241-246 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kim.R.: "Experimental studies on biochemical modulation targeting topoisomerase I and II in human tumor xenografts in nude mise" Int.J.Cancer. 50. 760-766 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 平林直樹: "固形腫瘍におけるMDR-1,トポイソメラーゼI,II遺伝子発現の臨床的意義" Oncologia. 26. 426-430 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nishiyama,M.: "Relevance of DT-diaphorase activity to mitomycin C(MMC)efficacy on human cancer cells:differences in in vitro and in vivo systems." Int.J.Cancer. 53. 1013-1016 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Aogi,K.: "Mechanism of cytotoxic activity of topoisomerase I inhibitor SN-38 in colon cancer cell lines." J.of Bacteriology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kim R.: "Expression of MDR-1, GST-pi, and topoisomerase II as an indicator of clinical response of adriamycin." Anticancer Research. 11. 429-432 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kim R.: "Clinical significance of P-glycoprotein expression analyzed by immunohistochemical staining in cancer tissues." The Japanese Journal of Surgery. 21. 590-593 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kim R.: "mRNA expression of topoisomerase II in human tumors and normal tissues." The Japanese Journal of Surgery. 21. 587-589 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Toge T.: "Current status of chemosensitivity tests and its problems." The J.Japanese Soc.of Clinical Surgery. 53. 751-757 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kim R.: "Factors contributing to adriamycin sensitivity in human xenograft tumors : the relationship between expression of the MDR-1, GST-pi, and topoisomerase II genes and tumor sensitivity to adriamycin." Anticancer Research. 12. 241-246 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kim R.: "Experimental studies on biochemical modulation targeting topoisomerase I and II in human tumor xenografts in nude mice." Int.J.Cancer. 50. 760-766 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hirabayashi N.: "Clinical significance of mRNA expression of MDR-1, topoisomerase I and II genes in solid tumors." Oncologia. 26. 426-430 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nishiyama M.: "Relevance of DT-diaphorase activity to mitomycin C(MMC) efficacy on human cancer cells : differences in in vitro and in vivo systems." Int.J.Cancer. 53. 1013-1016 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Aogi K.: "Mechanism of cytotoxic activity of topoisomerase I inhibitor SN-38 in colon cancer cell lines." J.of Bacteriology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 平林 直樹: "固形腫瘍におけるMDR-1,トポイソメラーゼI,II遺伝子発現の臨床的意義" Oncologia. 26. 426-430 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nishiyama,M.: "Relevance of DT-diaphorase activity to mitomycin C(MMC)efficacy on human cancer cells:differences in in vitro and in vivo systems." Int.J.Cancer. 53. 1013-1016 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 岩田 尚士: "ATP assayを利用した腫瘍温熱感受性試験の検討" Oncologia. 25. 330-336 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 平井 敏弘: "高齢者のがん治療における問題点 -高齢者胃がんの外科治療とその成績-" 広島医学. 45. 701-705 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ryungsa KIM: "mRNA Expression of Topoisomerase II in Human Tumors and Normal Tissues" The Japanese Journal of Surgery. 21. 587-589 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ryungsa KIM: "Expression of MDR1,GSTーπ and Topoisomerase II as an Indicator of Clinical Response to Adriamycin" ANTICANCER RESEARCH. 11. 429-432 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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