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Basic and Climicol Research for BCG Immunatherapy agoinst Bledd-Caner

Research Project

Project/Area Number 07671719
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

MIZUTANI Youichi  Kyoto University, Urology, Lecturer, 医学研究科, 助手 (10243031)

Co-Investigator(Kenkyū-buntansha) YOSHIDA Osamu  Kyoto University, Urology, Professor, 医学研究科, 教授 (70025584)
OKADA Yusaku  Kyoto University, Urology, Assistant Professor, 医学研究科, 助教授 (20127062)
TERACHI Toshiro  Kyoto University, Urology, Associate Professor, 医学研究科, 講師 (50207487)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1996: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsBladdr cancer / BCG / Immunity / Lymphocyte / Cytotoxicity / Autologors tumor / Fas / ADR / cytotoxicity / Immunity / T lymphocyte / NK cell / IL-6 / c-myc / G-CSF / lymphocyte
Research Abstract

The resistance of bladder cancer to anticancer chemotherapeutic agents remains a major problem. Hence, several immunotherapeutic approaches have been developed to treat the drug-resistant cancer cells. Fas antigen (Fas) and Fas ligand participate in T lymphocyte-and natural killer cell-mediated cytotoxicity, which are activated by BCG immunotherapy. Like Fas ligand, anti-Fas monoclonal antibody (mAb) induces apoptosis of the cells expressing Fas. This study has examined whether bladder cancer cells are sensitive to anti-Fas mAb-mediated cytotoxicity and whether anticancer agents synergize with anti-Fas mAb in cytotoxicity. The T24 human bladder cancer cell line constitutively expressed the Fas on the cell surface, however, T24 line was resistant to anti-Fas mAb. Treatment of T24 cells with anti-Fas mAb in combination with mitomycin C,methotrexate or 5-fluorouracil did not overcome their resistance to these agents. However, treatment of T24 cells with combination of anti-Fas mAb and adr … More iamycin (ADR) resulted in a synergistic cytotoxic effect. In addition, the ADR-resistant T24 cells (T24/ADR) was sensitive to treatment with combination of anti-Fas mAb and ADR.Synergy was also achieved in three other bladder cancer lines and four freshly derived human bladder cancer cells. Treatment with anti-Fas mAb in combination with epirubicin or pirarubicin also resulted in a synergistic cytotoxic effect on T24 cells. The mechanisms of synergy were examined. Intracellular accumulation of ADR,the expression of P-glycoprotein, or the expression of the anti-oxidant glutathione S transferase-pi mRNA was not affected by anti-Fas mAb. However, treatment with ADR enhanced the expression of Fas on T24 cells. This study demonstrates that treatment of bladder cancer cells with ADR sensitizes the cells to lysis by anti-Fas mAb. The synergistic effect obtained with established ADR-resistant bladder cancer cells and freshly isolated bladder cancer cells suggests that drug-resistant bladder cancer cells can be sensitized by ADR to Fas-Fas ligand-mediated cytotoxicity by lymphocytes. Furthermore, the sensitization required low concentrations of ADR,thus supporting the in vivo application of combination of drug and BCG immunotherapy in the treatment of drug-and/or BCG immunotherapy-resistant bladder cancer. Less

Report

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

Research Products

(28 results)

All Other

All Publications (28 results)

  • [Publications] Youichi Mizutani: "Sensitization of rlumen Renal Cell Caruinoma Cells to CDDP by Ann-IL-6 in Ab or ^-Anti-IL-6 Receptor in Ab" Caucer Research. 55. 590-596 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Youichi Miztani: "Enhanced suscephilyility of c-myc antifcnce oligonulofrade-truted human reral cell caruinora cells" Journal of Immurotherapy. 17. 78-87 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Youichi Mizutani: "Progrostrc significonce of ciruilrtiry aytoxic lyrploytes aginst antologace timoss in patients with blodder concer" The Journal of Urology. 155. 888-894 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Youichi Mizutani: "significence of uyfotoxic actinty of periplarel blsod lymphoys against antologous tuaor cells in patheys with blodder cencer" Cancer Biothorapy & Radio pharmaumtials. 11. 385-391 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Youichi Miztani: "Eyperssion of plctelet-denived endothlicl cell grouth fecfor in bladder cercitioma" Carar. 79. 1190-1194 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Youichi Miztani: "Do xour bicin sensitizes human bleddor carcinoma cells to Fus-radiated cido toxlity" Cancer. 79. 1180-1189 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mizutani, Y., Bonavida, B., Koishihara, Y., Akamatsu, K., Ohsugi, Y.and Yoshida, O.: "Sensitization of human renal cell carcinoma cells to cisdiamminedichloroplatinum (II) by anti-interleukin-6 monoclonal antibody or anti-interleukin-6-receptor monoclonal antibody" Cancer Research. 55. 590-596 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mizutani, Y., Fukumoto, M., Bonavida, B.and Yoshida, O.: "Enhanced susceptibility of c-myc antisense oligonucleotide-treated human renal cell carcinoma cells to lysis by peripheral blood lymphocytes." Journal of Immunotherapy. 17. 78-87 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mizutani, Y.and Yoshida, O.: "Prognostic significance of circulationg cytotoxic lymphocytes against autologous tumors in patients with urinary bladder cancer" Journal of Urology. 155. 888-894 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mizutani, Y., Okada, Y.and Yoshida, O.: "Significance of cytotoxic activity of peripheral blood lymphocytes against autologous tumor cells in patients with bladder cancer." Cancer Biotherapy & Radiotherapeutics. 11. 385-391 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mizutani, Y., Okada, Y.and Yoshida, O.: "Expression of platelet-derived endothelial cell growth factor in bladder carcinoma" Cancer. 79. 1190-1194 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mizutani, Y., Okada, Y., Fukumoto, M., Bonavida, B.and Yoshida, O.: "Doxorubicin sensitizes human bladder cancer cells to Fas-mediated cytotoxicity" Cancer. 79. 1180-1189 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Youichi Mizutani: "Prognostic Significance of Circulating Cytotoxic Lymphocytes against Autologons Tumors in Patients with Bladder Cancer" The Journal of Urology. 155. 888-894 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Youichi Mizutani: "Simultaneons Left Reinal Pelnic and Bilateral Ureteral Tumors Producing Carbohydrate Antigen 19-9" International Journal of Urology. 3. 231-233 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Youichi Mizutani: "Effect of Surgical Stress on Immune Function in Patients with Urologic Cancer" International Journal of Urology. 3. 426-434 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Youichi Mizutani: "Significance of Cytotoxic Activity of Peripheral Bloocl Lynphocytes against Autologons Tumor Cells in Patients with Biology Cancer" Cancer Biotherapy & Radiopharmaceaticals. 11. 385-391 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Youichi Mizutani: "Adriamycin Sensitizes Human Bladoler Cancer Cells to Fas-Mediated Cytotonicity" Cancer. (発表予定).

    • Related Report
      1996 Annual Research Report
  • [Publications] Youichi Mizutani: "Expression of Platelet-Derived Endothelial Cell Growth Factor in Bladcler Cancer" Cancer. (発表予定).

    • Related Report
      1996 Annual Research Report
  • [Publications] 水谷陽一: "最新癌化学療法" メディカルレビュー社, 10 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 水谷陽一: "現代医療" 現代医療社(発表予定),

    • Related Report
      1996 Annual Research Report
  • [Publications] Youichi Mizutani: "Sensitization of Human Renal cell carcinoma cells to coop by anti-IL6 mAb or anti-IL6 receptor mAb" Cancer Research. 55. 590-596 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Youichi Mizutani: "Enhanced susceptibility of c-myc antisense oligonucleotide-treated human renal cell carcinoma cells" Journal of Immunotherapy. 17. 78-87 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Y. Mizutani: "Serum G-CSF levels in patients with urinary bladder and various urological malignancies" Britich Journal of Urology. 76. 580-586 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Youichi Mizutani: "Prognostic significance of cirivelating cytotoxic lymphoagtes against autologous tumors" The Journal of Urology. (発表予定).

    • Related Report
      1995 Annual Research Report
  • [Publications] Youichi Mizutani: "A case report of simultaneous left renal pelvic and bilateral ureteral tumors" International Journal of Urology. (発表予定).

    • Related Report
      1995 Annual Research Report
  • [Publications] 水谷陽一: "Chemoimmunotherapyに関する基礎的研究" Biotherapy. 9. 425-426 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 水谷陽一: "癌化学療法のあり方 1996" メディカルレビュー社(発表予定),

    • Related Report
      1995 Annual Research Report
  • [Publications] 水谷陽一: "外科基本手技マニュアル" 永井書店(発表予定),

    • Related Report
      1995 Annual Research Report

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

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