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Analysis of the immune response of tumor-bearing host at the immunochemotherapy -from the viewpoint of optimum combination of chemotherapy and immunotherapy -

Research Project

Project/Area Number 12671212
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKanazawa University

Principal Investigator

FUJIMOTO Toshihiro  Kanazawa University, Medical School, Assistant Professor, 医学部・附属病院, 講師 (00242561)

Co-Investigator(Kenkyū-buntansha) MAI Masayoshi  Kanazawa University, Cancer Research Institute, Professor, がん研究所, 教授 (80092807)
TAKAHASHI Yutaka  Kanazawa University, Cancer Research Institute, Associate Professor, がん研究所, 助教授 (10179541)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsIrinotecan(CPT-11) / OK-432 / Th1 / IL-12 / immunochemotherapy / tumor bearing state / immunochemc therapy
Research Abstract

Chemotherapy with lower dose of irinotecan (CPT-ll) exerts larger antitumor effect. In this study, SN-38, the active metabolite of CPT-ll, exerted dose-dependent inhibition of interferon (IFN)-γ and interleukin (IL)-10 production induced by streptococcal preparation OK-432 in mouse splenocytes. In contrast, the optimum concentration of SN-38 (0.4-0.8(μg/ml) increased IL-6 and IL-12 production by OK-432 activated macrophages. In tumor-bearing mice (C57BL/6 mice bearing with B16 melanoma), CPT-11 inhibited tumor growth and OK-432 had an additive antitumor effect with CPT-11. Investigation of cytokine production showed that CPT-11 treatment principally inhibited IL-12 and IFN-γ production, which was improved by the combined administration with OK-432. These results indicate that CPT-11 inhibits type-1 T helper (Th1) cells despite its potential to stimulate macrophages and that OK-432 enhances the antitumor activity of CPT-11 by increasing Th1-cytokine production (Anticancer Research 21 : 2505-2510, 2001).
In the treatment for the peritoneal metastasis of gastric carcinoma, we may control disseminated cancer cells by intraperitoneal immunochemotherapy using MMC and OK432 in patients with curative resection (Oncology, 2002, in press).
Briefly, these results have demonstrated the efficacy of the combination of chemotherapy and immunotherapy.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] 藤本敏博: "胃癌の腹膜播種に対するMMC+OK-432腹腔内投与の臨床効果"Therapeutic Research. 21. 1940-1945 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Fujimoto, et al.: "The effect of OK-432 on the cytokine production of the tumor bearing mouse splenocytes"Biotherapy. 14. 528-528 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] X.Wang, T.Fujimoto, et al.: "Streptococcal preparation OK-432 enhances the antitumor activity of CPT-11 by increasing Th1 cytokine production in tumor-bearing mice"Anticancer Research. 21. 2505-2510 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Fujimoto, et al.: "Evaluation of intraoperative intraperitoneal cytology for advanced gastric carcinoma"Oncology. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 藤本敏博, 他: "肝転移、メカニズムと臨床「免疫療法」"医学書院. 228 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujimoto T: "The efficacy of intrapertioneal administration of MMC and OK-432 against peritoneal metastasis of gastric cancer"Therapeutic Research. 21. 1940-1945 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wang X, Fujimoto T, Zhang B, Shimizu A, and Mai M: "The effect of OK-432 on the cytokine production of the tumor bearing mouse splenocytesy"Biotherapy. 14. 528 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wang X, Fujimoto T, Zhang B, and Mai M: "Streptococcal preparation OK-432 enhances the antitumor activity of CPT-11 by increasing Th1 cytokine production in tumor-bearing mice"Vrticancer Research. 21. 2505-2510 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujrmoto T, Zhang B, Minami S, Wang X, Takahashi Y, and Mai M: "Evaluation of intraoperative intraperitoneal cytology for advanced gastric carcinoma"Oncology. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujimoto T: "Imraunotherapy for liver metastasis. Liver metastasis- its mechanism and clinical experience. (Mai M, Seiki M and Takahashi Y ed.)"Igaku-shoin, Tokyo. 212-219 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 藤本 敏博: "胃癌の腹膜藩種に対するMMC+OK-432腹腔内投与の臨床効果"Therapeutic Research. 21. 1940-1945 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Fujimoto, et al.: "The effect of OK-432 on the cytokine production of the tumor bearing mouse splenocytes"Biotherapy. 14. 528-528 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] X.Wang, T.Fujimoto, et al.: "Streptococcal preparation OK-432 enhances the antitumor activity of CPT-11 by increasing Th1 cytokine production in tumor-bearing mice"Anticancer Research. 21. 2505-2510 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Fujimoto, et al.: "Evaluation of intraoperative intraperitoneal cytology for advanced gastric carcinoma"Oncology. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 藤本敏博, 他: "肝転移、メカニズムと臨床「免疫療法」"医学書院. 228 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] 藤本敏博 他: "胃癌の腹膜播種に対するMMC+OK-432腹腔内投与の臨床効果"Therapeutic Research. 21. 1940-1945 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Fujimoto el al.: "The effect of OK-432 on the cytokine production of the tumor bearing mouse splenocytes."Biotherapy. 14. 528-528 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 藤本敏博: "肝転移,メカニズムと臨床「免疫療法」"医学書院. 212-219 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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