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2005 Fiscal Year Final Research Report Summary

In vivo analysis of micrometastasis formation and subsequent peritoneal dissemination using GFP-tagged gastric cancer cell lines.

Research Project

Project/Area Number 16590336
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

NAKANISHI Hayao  Aichi Cancer Center research Institute, Division of Oncological Pathology, Section Head, 腫瘍病理学部室長, 室長 (20207830)

Project Period (FY) 2004 – 2005
KeywordsGastric cnacer / Peritoneal metastasis / Mecirometastasia / TNF-alpha / Knockout mouse / Angiogenesis
Research Abstract

Peritoneal metastasis is the most important pattern of recurrence after curative resection in gastric cancer. The research goal of this project is to understand the molecular mechanisms of micrometastasis formation and subsequent peritoneal dissemination, and developed a new therapeutic approaches to protect patients from peritoneal recurrence. During this period (2004-2006), we demonstrated several findings as follows. We investigated whether peritoneal dissemination can be suppressed by the blockade of TNF-α using two mouse models such as TNF-α knockout (KO) mice/bone marrow chimera mice model and human gastric cancer xenograft model. We found that GFP-tagged Lewis carcinoma cells (P-29) disseminated into the whole peritoneal cavity including abdominal wall peritoneum in wild type C57BL mice after intraperitoneal injection, whereas in the TNF-α KO mice, tumor cells only metastasized to the omentum and mesentery in a milky spot-dependent manner without dissemination as well as growth … More stimulation, leading to the significant longer survival of KO mice than wild type mice. This ristricted peritoneal metastasis was canceled in chimeric KO mice transplanted with wild type bone marrow, in which TNF-α expressing leukocyte recruited into the peritoneal cavity. Addition of intraperitoneal chemotherapy with pacitaxel inhibited tumor growth in the peritoneal cavity and significantly increased survival time of KO mice rather than wild type mice because of inhibition of both growth and peritoneal dissemination of tumor cells. Furthermore, peritoneal dissemination of human gastric cancers tagged with GFP in nude mice was partially inhibited by the treatment with anti human TNF-α antibody (infliximab), resulting in a longer survival of the treated mice. These results indicate that TNF-α derived from host inflammatory leukocytes as well as tumor cells in the peritoneal cavity is responsible for peritoneal dissemination of tumor cells and suggest that anti TNF-α therapy in combination with chemotherapy would be a new potential therapeutic modality for protection of peritoneal dissemination and therefore prevention of peritoneal recurrence after curative surgery in gastric cancer patients. We are also developing ant-angiogenic therapy targeting to micrometastais with humanized anti-VEGE monoclonal antibody as well as a new drug delivery system to the peritoneal micrometastasis using mannose-coated liposome Less

  • Research Products

    (15 results)

All 2006 2005 2004

All Journal Article (14 results) Book (1 results)

  • [Journal Article] Biological significance of isolated tumor cells and micro metastasis in lymph nodes evaluated using a green fluorescent protein (GFP)-tagged human gastric cancer cell line.2006

    • Author(s)
      Yokoyama H, Nakanishi H, Kodera Y. et al.
    • Journal Title

      Clin. Cancer Res. 12(2)

      Pages: 361-68

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Biological significance of isolated tumor cells and micrometastasis in lymph nodes evaluated using a green fluorescent protein (GFP)-tagged human gastric cancer cell line.2006

    • Author(s)
      Yokoyama H., Nakanishi H., Kodera Y.et al.
    • Journal Title

      Clin.Cancer Res. 12(2)

      Pages: 631-368

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Immunocytochemical detection unsing CDX2. An aid for discerning tumor involvement in ascites cytology.2006

    • Author(s)
      Kobayashi M., Ueyama Y, Nakanishi H.et al.
    • Journal Title

      Cancer (Cancer Cytopathology) 12(2)

      Pages: 361-368

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Prognostic significance of intraperitoneal cancer cells in gastric carcinoma : detection of cytokeratin 20 mRNA in peritoneal washes, in addition to detection of carcinoembryonic antigen.2005

    • Author(s)
      Kodera Y, Nakanishi H, Ito S et al.
    • Journal Title

      Gastric Cancer. 8(3)

      Pages: 142-8

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Efficacy of intraperitoneal chemotherapy with paclitaxel targeting peritoneal micro metastasis as revealed by GFP-tagged human gastric cancer cell lines in nude mice.2005

    • Author(s)
      Ohasi.N, Kodera.Y, Nakanishi H.et al.
    • Journal Title

      Int. J. Oncol. 27(9)

      Pages: 637-44

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Prospective validation of quantitative CEA mRNA detection in peritoneal washes in gastric carcinoma patients.2005

    • Author(s)
      Ito S, Nakanishi H, Kodera Y. et al.
    • Journal Title

      Br. J. Cancer 93(9)

      Pages: 986-92

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Prognositc siginificance of intraperitoneal cancer cells in gastric carcinoma : detection of cytokeratin 20 mRNA in peritoneal washes, in addition to detection of carcinoembryonic antigen2005

    • Author(s)
      Kodera Y, Nakanishi H, Ito S et al.
    • Journal Title

      Gastric Cancer 8

      Pages: 142-148

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Efficacy of intraperitoneal chemotherapy with paclitaxel targeting peritoneal micrometastasis as revealed by GFP-tagged human gastric cancer cell line in nude mice2005

    • Author(s)
      Ohashi.N, Kodera.Y, Nakanishi H.et al.
    • Journal Title

      Int.J.Oncol. 27(9)

      Pages: 637-644

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Prospective validation of quantitative CEA mRNA detection in peritoneal washes in gastric carcinoma patients2005

    • Author(s)
      Ito S., Nakanishi H., Kodera Y.et al.
    • Journal Title

      Br.J.Cancer 93(9)

      Pages: 986-992

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] "腹膜播種に対する洗浄細胞診への術中迅速遺伝子診断の応用"胃腸・大腸癌II-悪性度診断2005

    • Author(s)
      中西速夫, 小寺泰弘, 伊藤誠二, 山村義孝, 加藤知行, 立松正衞
    • Journal Title

      病理と臨床(文光堂) 23巻9号

      Pages: 945-953

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] TNF-alpha promotes progression of peritoneal metastasis as demonstrated using a green fluorescence protein (GFP)-tagged human gastric cancer cell line2004

    • Author(s)
      Mochizuki, Y, Nakanishi, H, Kodera, Y. et al.
    • Journal Title

      Clin. Exp. Metastasis 21

      Pages: 39-47

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Detection of Disseminated Cancer Cells in Linitis Plastica type Gastric Carcinoma.2004

    • Author(s)
      Kodera Y, Nakanishi H, Ito S et al.
    • Journal Title

      Jpn. J. Clin. Oncol. 34

      Pages: 525-31

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] TNF-alpha promotes prgression of peritoneal metastasis as demonstrated using a green fluorescence protein (GFP)-tagged human gastric cancer cell line2004

    • Author(s)
      Mochizuki, Y., Nakanishi, H., Kodera, Y.et al.
    • Journal Title

      Clin.Exp.Metastasis 21

      Pages: 39-47

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Detection of Disseminates Cancer Cell in Linitis Plastica type Gastric Carcinoms.2004

    • Author(s)
      Kodera Y., Nakanishi H., Ito S et al.
    • Journal Title

      Jpn.J.Clin.Oncol. 34

      Pages: 525-531

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] "腹膜播種に対する洗浄細胞診への術中迅速遺伝子診断の応用"胃癌・大腸癌II-悪性度診断2005

    • Author(s)
      中西速夫, 小寺泰弘, 伊藤誠二, 山村義孝, 加藤知行, 立松正衛
    • Total Pages
      945-953
    • Publisher
      文光堂、病理と臨床
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2007-12-13  

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