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Antimetastatic therapy by matrix metalloproteinase inhibitors

Research Project

Project/Area Number 10671216
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

OTANI Yoshihide  Keio University, School of Medicine, Assistant Professor, 医学部, 専任講師 (20168983)

Co-Investigator(Kenkyū-buntansha) KAMEYAMA Kaori  Keio University, School of Medicine, Instructor, 医学部, 助手 (10245467)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsGastric cancer / peritoneal dissemination / metastasis / invasion / matrix metalloproteinases / MMP / G.I.tract cancer / tumor
Research Abstract

Cancer cells degradate extracellular matrix around cancer nests during invasion and metastasis. We have reported the role of matrix metalloproteinases in invasion and metastasis using gastrointestinal tract cancers. Postoperative survival of gastric cancer patients with peritoneal dissemination is very poor. We investigated therapeutic efficacy of newly developed, synthetic MMP inhibitors.
First, nude mice peritoneal dissemination model of human gastric cancer cell line was established. A gastric carcinoma cell line (TMK-1;5x10ィイD15ィエD1/body) was injected intraperitoneally into nude mice. Subsequently, R-94138 (30 mg/kg), CDDP (3 mg/kg) and MMC (2 mg/kg) were administered alone or in combination of two of these agents into the mice. They were sacrificed 5 weeks after the injection, and therapeutic efficacy was evaluated by counting the number of peritoneal nodules. R-94138 significantly decreased the formation of peritoneal nodules and the combination of R-94138 and MMC significantly decreased the number of peritoneal nodules compared with a control or other combination groups.
In conclusion, MMP inhibitor suppressed the peritoneal metastasis in nude mice model. The possibility of clinical application of MMP inhibitor was evidenced in this study.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Igarashi N, Kubota T, Otani Y, et al: "Preventive effect of matrix metalloproteinase inhibitor, R-94138, in combination with mitomycin C or cisplatin on partoneal dissemination of human gastric cancer cell line TMK-1 in nude mice."Jpn. J. Cancer Res.. 90. 116-121 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 大谷吉秀ほか: "消化器癌の浸潤転移における間葉系細胞の重要性-細胞外マトリックス破壊から見て"日消外会誌. 31. 990-994 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 大谷吉秀ほか: "消化器癌転移抑制におけるMMP活性阻害の意義-臨床応用への展望"Biotherapy. 13. 679-685 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 木全大、大谷吉秀ほか: "ヌードマウス胃癌腹膜播種モデルにおけるマトリックス分解酵素阻害剤TA-2516(Marimastat)の腫瘍抑制効果"日外会誌. 100. 363 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshihide Otani, et al: "Expression of matrix metalloproteinases in gastric carcinoma and possibility of clinical application of matrix metalloproteinase inhibitor in vivo."Ann NY Acad. Sci. 878. 541-543 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 大谷吉秀: "MMP活性阻害による新しい胃癌転移治療"消化器科. 30. 40-45 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 大谷吉秀他: "コラーゲン代謝と消化器癌転移-基礎研究の臨床応用"医学書院 東京. 197〜206 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Naoki Igarashi, Tetsuro Kubota, Yoshihide Otani, et al.: "Preventive effect of matrix metalloproteinase inhibitor, R-94138, in combination with mitomycin C or cisplatin on peritoneal dissemination of human gastric cancer cell line TMK-1 in nude mice"Jpn J Cancer Res. 90. 116-121 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshihide Otani, et al.: "Expression of matrix metalloproteinases in gastric carcinoma and possibility od clinical application of matrix metalloproteinase inhibitor in vivo"Ann NY Acad Sci. 878. 541-543 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 大谷吉秀ほか: "消化器癌転移抑制におけるMMP活性阻害の意義-臨床応用への展望"Biotherapy. 13・6. 679-685 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 木全 大、大谷吉秀ほか: "ヌードマウス胃癌腹膜播種モデルにおけるマトリックス 分解酵素阻害剤TA-2516(Marimastat)の腫瘍抑制効果"日外会誌. 100・5. 363 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshihide Otani,et al: "Expression of matrix metalloproteinases in gastric carcinoma and possibility of clinical application of matrix metalloproteinase inhibitor in vivo"Ann NY Acad Sci. 878. 541-543 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 大谷吉秀ほか: "MMP活性阻害による新しい胃癌転移治療"消化器科. 30・1. 40-45 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Igarashi N,Kubota T,Otani Y,et al.: "Preventive effect of matrix metalloproteinase inhibitor, R-94138, in combination with mitomycin C of cisplatin on peritoneal dissemination of human gastric cancer cell line TMK-1 in nude mice." Jpn J Cancer Res. 90・1. 116-121 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 大谷吉秀ほか: "消化器癌の浸潤転移における間葉系細胞の重要性-細胞外マトリックス破壊からみて" 日消外会誌. 31・4. 990-994 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 大谷吉秀ほか: "Matrix metalloproteinase(MMP)の研究および臨床の現状" 癌と化学療法. 25・7. 957-964 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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