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Study on the multiple drug resistant mechanisms in clinical materials of lung cencer

Research Project

Project/Area Number 07670646
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

ISOBE Hiroshi  Hokkaido Univ., Medical Hospital, Assistant, 医学部・附属病因, 助手 (90241322)

Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1995: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsLung Cancer / Drug Resistance / Topoisomerase / Confocal Laser Microscopy / p-glycoprotein / トポインメラーゼ / P-glycoprotein / 共焦点走査型レーザー顕微鏡
Research Abstract

Topoisomerase II alpha content, topoisomerase II catalytic activity and drug sensitivities to the topoisomerase inhibitors, doxorubicin, and etoposide, were examined in human lung cencer cell lines to determine the relationship between topoisomerase II and drug sensitivities to the topoisomerase II inhibitors. Moreover, the relationship between these biochemical analyzes and topoisomerase II immunostaining in cytosp=in preparations was examined. The difference in drug sensitivities to doxorubicin and etoposide in human lung cencer cell lines is not explainable by the topoisomerase II alpha levels and topoisomerase II catalytic activity. The percentages of positive cells for topoisomerase II immunostaining are compatible with the levels of topoisomerase II alpha content or topoisomerase II catalytic activity. Our results indicate that topoisomerase II immunostaining can be utilized in place of biochemical analysis. It is difficult to collect sufficient cells for these biochemical analyzes from lung cencer patients by transbronchial brushing or aspiration, or pleural effusions. Therefore, we examined the intracellular drug distribution using a confocal laser scanning microscopy. In this study, the cells with intranuclear drug accumulation are more sensitive than those with extranuclear drug accumulation. Moreover, the resistant cell line showed extranuclear distribution of topoisomerase II enzyme detected by immunostaining method using the confocal laser scanning microscopy. The confocal laser scanning microscopy is useful to detect the drug sensitivity and resistant in clinical samples those are usually small amount.
These methods are applied in the patients with malignant pleural effusion after intra-pleural injection of anthracyclines. The patients with intranuclear drug accumulation revealed the good control of malignant effusion. We conclude that this method is useful in the estimation of drug sensitivity of lung cencer cells, especially the clinical materials.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report

Research Products

(11 results)

All Other

All Publications

  • [Publications] 磯部宏: "フローサイトメトリーによる抗癌剤の細胞内取り込みの測定" Cytometry Research. 5. 31-33 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 山崎浩一: "Flow cytometryおよび共焦点レーザー顕微鏡による薬剤耐性機序の検討" Cytometry Research. 5. 57-62 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kohichi Yamazaki: "Quantitative immunoaytochemicalassays of topoisamerase II in lung adenocarcinoma cell lines" Acta Oncologica. 35. 417-423 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kohichi Yamazaki: "Topoisomerase IIα content and topoisomerase II catalytic activity cannot explain dnig sensitivities to topoisomerase II inhinitors in lung cancer cell lines" Cancer Chemother Pharmacol. 39. 192-198 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hiroshi Isobe: "Flow cytometric detection of cellular anti-cancer drug accumulation" Cytometry Research. 5-2. 31-33 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kohichi Yamazaki: "Flow cytometric and confocal laser microscopic analysis of doxorubicin resistance mechanisms in a human small cell lung cancer cell line" Cytometry Research. 5-2. 57-62 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kohichi Yamazaki: "Quantitative immunocytochemical assays of topoisomerase II in lung adenocarcinoma cell lines" Acta Oncologica. 35-4. 417-423 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Koichi Yamazaki: "Topoisomerase II alpha content and topoisomerase II catalytic activity cannot explain drug sensitivities to topoisomerase II in lung cancer cell lines" Cancer Chemother Pharmacol. 39. 192-198 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kohichi Yamazaki: "Quantitative immunocytochemical assays of topt aisome rase II in lmg adenocarcinoma cell lines" Acta Oncologica. 35. 417-423 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 磯部 宏: "フローサイトメトリーによる抗癌剤の細胞内取り込みの測定" Cytometry Research. 5. 31-33 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 山崎 浩一: "Flow cytometryおよび共焦点レーザー顕微鏡による薬剤耐性機序の検討" Cytometry Research. 5. 57-62 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-03-31   Modified: 2016-04-21  

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