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Mechanisms responsible for peritoneal metastasis and lymph node metastasis in scirrhous gastric carcinoma

Research Project

Project/Area Number 13470260
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

HIRAKAWA Kosei  Osaka City University, Graduate School of Medicine Department :Surgical Oncology, Professor, 大学院・医学研究科, 教授 (40188652)

Co-Investigator(Kenkyū-buntansha) YOSHIRO Masakazu  Osaka City University, Graduate School of Medicine Department : Surgical Oncology, Lecturer, 大学院・医学研究科, 講師 (60305638)
Project Period (FY) 2001 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsgrowth activity / fibroblasts / ICAM1 / Peritoneal metastasis / scirrhous gastric carcinoma / lymph node metastasis / スキルス胃癌 / リンパ筋転移 / 腹膜転移 / 接着分子 / CD44H / インテグリン / 接着ペプチド
Research Abstract

Prognosis of advanced stage gastric carcinoma remains poor because of the frequent incidence of metastasis. We examined the effect of adhesion polypeptides on the adhesion and invasiveness of gastric cancer cell lines. Peritoneal-seeding cell line, OCUM-2MD3, was established from a poorly seeding human scirrhous gastric carcinoma cell line, OCUM-2M. Both α2β1 and α3β1 integrin expression was markedly increased on OCUM-2MD3 cells compared with OCUM-2M cells, and the adhesion ability of OCUM-2MD3 cells to the extracellular matrix (ECM) was also significantly higher than that of OCUM-2M cells. The adhesion polypeptides, YIGSR and RGD significantly inhibited the adhesion of OCUM-2MD3 cells to the submesothelial ECM, while not inhibiting the adhesiveness of OCUM-2M cells and two well differentiated human gastric cell lines, MKN-28 and MKN-74. The YIGSR and RGD peptides also significantly inhibited the invasiveness of OCUM-2MD3 cells. The survival of nude mice with peritoneal dissemination g … More iven YIGSR sequence intraperitoneally was obviously longer than that of untreated mice. These polypeptides appear to block the binding of integrins, which are expressed on OCUM-2MD3 cells, to the submesothelial ECM. The peritoneal injection of adhesion polypeptides may be a new therapy against the dissemination of scirrhous gastric cancer, and may be useful for the prevention of dissemination in high-risk patients.
We transfected ICAM-1 genes into gastric cancer cell line, 2MLN, and analyzed the effect on the lymph node metastasis of the transduction of ICAM-1 in vitro and in vivo. Lymph node metastases caused by 2MLN/ICAM cells were recognized as being fewer in number and smaller, while many lymph node metastases caused by 2MLN cells were recognized. These findings indicate that ICAM-1 gene might be a tumor suppressor gene that is important for lymph node metastasis, and that ICAM-1 gene transduction could prove to be an effective gene therapy for lymph node metastasis of gastric cancer. Less

Report

(5 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (22 results)

All 2005 2004 2003 Other

All Journal Article (14 results) Publications (8 results)

  • [Journal Article] CD54 Expression Is Predictive for Lymphatic Spread in Human Gastric Carcinoma.2005

    • Author(s)
      Yashiro M
    • Journal Title

      Dig Dis Sci. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] K-ras mutation influences macroscopic features of gastric carcinoma.2005

    • Author(s)
      Yashiro M
    • Journal Title

      J Surg Res 124

      Pages: 74-78

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] CD54 Expression Is Predictive for Lymphatic Spread in Human Gastric Carcinoma.2005

    • Author(s)
      Yashiro M, Sunami T, Hirakawa K
    • Journal Title

      Dig Dis Sci. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] K-ras mutation influences macroscopic features of gastric carcinoma.2005

    • Author(s)
      Yashiro M, Nishioka N, Hirakawa K
    • Journal Title

      J Surg Res 124

      Pages: 74-78

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ICAM-2 gene therapy for peritoneal dissemination of scirrhous gastric carcinoma2004

    • Author(s)
      Tanaka H
    • Journal Title

      Clin Cancer Res 10

      Pages: 4885-4892

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Novel models for human scirrhous gastric carcinoma in vivo.2004

    • Author(s)
      Takemura S
    • Journal Title

      Cancer Sci 95

      Pages: 893-900

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Is a lymph node detected by the dye-guided method a true sentinel node in gastric cancer?2004

    • Author(s)
      Osaka H
    • Journal Title

      Clin Cancer Res 10

      Pages: 6912-6918

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ICAM-2 gene therapy for peritoneal dissemination of scirrhous gastric carcinoma.2004

    • Author(s)
      Tanaka H, Yashiro M, Sunami T, Sakate Y, Kosaka K, Hirakawa K
    • Journal Title

      Clin Cancer Res 10

      Pages: 4885-4892

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Novel models for human scirrhous gastric carcinoma in vivo.2004

    • Author(s)
      Takemura S, Yashiro M, Sunami T, Tendo M, Hirakawa K
    • Journal Title

      Cancer Sci 95

      Pages: 893-900

    • NAID

      10014197818

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Is a lymph node detected by the dye-guided method a true sentinel node in gastric cancer?2004

    • Author(s)
      Osaka H, Yashiro M, Sawada T, Katsuragi K, Hirakawa K
    • Journal Title

      Clin Cancer Res 10

      Pages: 6912-6918

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ICAM-2 Gene Therapy for Peritoneal Dissemination of Scirrhous Gastric Carcinoma2004

    • Author(s)
      Tanaka H, Yashiro M, Hirakawa K, et al.
    • Journal Title

      Clinical Cancer Research 10

      Pages: 4885-4892

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Usefulness of inhibiting The Lymph Node Metastasis in Human Gastric Carcinoma by B7-1 Gene Transfection2004

    • Author(s)
      Sakate Y, Yashiro M, Hirakawa K, et al.
    • Journal Title

      Journal of Surgical Research 122

      Pages: 89-95

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Keratinocyte growth factor produced by gastric fibroblasts specifically stimulates proliferation kf cancer cells from scirrhous gastric carcinoma.2003

    • Author(s)
      Nakazawa K
    • Journal Title

      Cancer Res 63

      Pages: 8848-8852

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Keratinocyte growth factor produced by gastric fibroblasts specifically stimulates proliferation of cancer cells from scirrhous gastric carcinoma.2003

    • Author(s)
      Nakazawa K, Yashiro M, Hirakawa K
    • Journal Title

      Cancer Res 63

      Pages: 8848-8852

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Nakazawa K, Yashiro M, Hirakawa K: "Keratinocyte growth factor produced by gastric fibroblasts specifically stimulates proliferation of cancer cells from scirrhous gastric carcinoma"Cancer Res.. 63. 8848-8852 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirakawa K, Yashiro H, et al.: "Tranilast (N-3,4-dimethoxycinamoyl anthranilic acid) : a novel inhibitor of invasion -stimulating interaction between gastric cancer cells and orthotopic fibroblasts"Anticancer Res.. 23. 3899-904 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirakawa K, Yashiro M, et al.: "An opposing view on WWOX protein function as a tumor suppressor"Cancer Res.. 63. 63:8629-63:8633 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 八代正和, 平川弘聖: "胃癌診断のコツ-遺伝子診断-"胃癌診療の基本(中山書店・初版). 113-120 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 八代正和, 平川弘聖: "間質細胞との相互作用からみたスキルス胃癌の分子標的治療"Surgery Frontier. 9. 95-100 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tanaka H, Yashiro M, Hirakawa K: "Lipid-mediated gene transfection of intercellular adhesion molecule-1 suppresses the peritoneal metastasis of gastric carcinoma"International Journal of Molecular Medicine. 10. 613-617 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hippo Y.: "Differential gene expression profiles of scirrhous gastric cancer cells with high metastatic potential to peritoneum or lymph nodes."Cancer Research. 61. 889-895 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsuoka T: "Effect of a Matrix metalloproteinase inhibitor on a lymph node metastatic model of gastric cancer cells"J. Exp. Clin. Cancer Res.. 20,2. 213-218 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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