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2004 Fiscal Year Final Research Report Summary

Development of multimodal gene therapy for gastrointestinal cancer using in vivo electroporation

Research Project

Project/Area Number 14370377
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

MATSUBARA Hisairo  Chiba Univ., Graduate School of Med., Assistant Professor, 大学院・医学研究院, 講師 (20282486)

Co-Investigator(Kenkyū-buntansha) OCHIAI Takenori  Chiba Univ., Graduate School of Med., Professor, 大学院・医学研究院, 教授 (80114255)
GUNJI Yoshio  Chiba Univ., Graduate School of Med., Associate Professor, 大学院・医学研究院, 助教授 (60241957)
TAGAWA Masatoshi  Chiba Cancer Center, Research Inst., Director, 研究局, 部長 (20171572)
MIYAZAKI Shin-ichi  Chiba Univ., University Hospital, Assistant Professor, 医学部附属病院, 助手 (40334198)
URASHIMA Tetsuro  Chiba Univ., University Hospital, Assistant Professor, 医学部附属病院, 助手 (80375625)
Project Period (FY) 2002 – 2004
Keywordsgene therapy / in vivo electroporation / gastrointestinal cancer / p53 gene / suicide gene / cytokine
Research Abstract

The preparation of cDNA of interleukin-21 and-23 which is a new cytokine gene was done. It could confirm that powerful tumor immunity was induced by transducing these new cytokine genes to the tumor cells. And, as for human esophageal cancer transplantation model as well which a nude mice was used for, the effect on an anti-tumor activity of IL-21 was confirmed. The utility of the HSV-tk gene which is promoted by tumor specific mini-promoter was examined. The most interesting effect of HSV-tk gene therapy is the by-stander effect, a phenomenon allowing the killing of untransduced cells. By using the minimal promoter region of midkine to drive HSV-tk gene, and in vivo electroporation to transduce the IL-21 DNA into the tumors, this comibination strategy produces an efficient gene therapy with improved safety.
in vivo electroporatio under the view adds a limitation to that utility and clinical application range gets narrow. The clinical trials of in vivo electroporation using anticancer d … More rugs until now was used for is limited to the subcutaneous tumor. Therfore the new electrode which could be used under the fiberscope was developed, in vivo electroporation to the esophagus or the liver under thoracotomy or laparotomy in swine model didn't give it a physiological effect and it could be carried out safely. These results caused to clinical application. The electrode which could be used by fiberscope or under the scopic operation was improved. And that prototype was completed.At present, an application for a patent is being prepared.
As for the combination with the gene transfer, a very high gene expression is expected so that histone deacethyl taransferase inhibitor (FK226) may strengthen the transcription of the transfected gene. One of the tumor suppressor genes was induced by FK226, and we confirmed that effect on an anti-tumor activity was shown in the human esophageal cancer cells. It will be analyzed about the reinforcement action of the effect on an anti-tumor of cytokine genes and the effect on vaccine by the combination of in vivo electroporation using FK226. Less

  • Research Products

    (12 results)

All 2004 2003

All Journal Article (12 results)

  • [Journal Article] Expression of the interleukin-21 and -23 in human esophageal tumors produced Antitumor effects in nude mice.2004

    • Author(s)
      Shan B., Yu L., Shimozato O., Li Q., Tagawa M.
    • Journal Title

      Anticancer Res 24

      Pages: 79-82

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Synergistic antitumor effect of antiangiogenic factor genes on colon 26 produced by low-voltage electroporation.2004

    • Author(s)
      Uesato M., Gunji Y, Tomonaga T, Miyazaki S, Matsubara H, et al.
    • Journal Title

      Cancer Gene Ther 11・9

      Pages: 625-632

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expression of the interleukin-21 and -23 in human esophageal tumors Produced antitumor effects in nude mice.2004

    • Author(s)
      Shan B., Yu L., Shimozato O., Li Q., Tagawa M.
    • Journal Title

      Anticancer Res 24

      Pages: 79-82

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Synergistic antitumor effect of antiangiogenic factor genes on colon 26 produced by low-voltage electroporation.2004

    • Author(s)
      Uesato M, Gunji Y, Tomonaga T, Miyazaki S, Matsubara H, et al.
    • Journal Title

      Cancer Gene Ther 11

      Pages: 625-632

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] 食道癌の遺伝子治療2003

    • Author(s)
      松原 久裕, 島田 英昭, 落合 武徳
    • Journal Title

      医学と薬学 50

      Pages: 392-398

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Progress of gene therapy for esophageal cancer in Japan2003

    • Author(s)
      Matsubara H, Ochiai T.
    • Journal Title

      Gan To Kagaku Ryoho 30

      Pages: 944-944

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Possible Involvement of Antitumor Immunity in the Eradication of Colon 26 Induced by Low-Voltage Electrochemotherapy with Bleomycin2003

    • Author(s)
      Miyazaki S, Gunji Y, Matsubara H, Uesato M, Ochiai T. et al.
    • Journal Title

      Surg Today 33

      Pages: 39-44

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Preoperative serum midkine concentration is a prognostic marker for esophageal squamous cell carcinoma.2003

    • Author(s)
      Shimada H, Nabeya Y, Tagawa M, Okazumi S, Matsubara H, Ochiai T., et al.
    • Journal Title

      Cancer Sci. 94・7

      Pages: 628-632

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Progress of gene therapy for esophageal cancer in Japan.2003

    • Author(s)
      Matsubara H, Ochiai T.
    • Journal Title

      Gan To Kagaku Ryoho 30

      Pages: 944-949

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Possible Involvement of Antitumor Immunity in the Eradication of Colon 26 Induced by Low-Voltage Electrochemotherapy with Bleomycin.2003

    • Author(s)
      Miyazaki S, Gunji Y, Matsubara H, Uesato M, Ochiai T. et al.
    • Journal Title

      Surg Today 33

      Pages: 39-44

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Preoperative serum midkine concentration is a prognostic marker for esophageal squamous cell carcinoma.2003

    • Author(s)
      Shimada H, Nabeya Y, Tagawa M, Okazumi S, Matsubara H, Ochiai T., et al.
    • Journal Title

      Cancer Sci 94

      Pages: 628-632

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression of the interleukin-21 gene in murine colon carcinoma cells generates systemic immunity in the inoculated hosts.2003

    • Author(s)
      Ugai S, Shimozato O, Kawamura K, Wang YQ, Yamaguchi T, Saisho H, Sakiyama S., Tagawa M.
    • Journal Title

      Cancer Gene Ther. 10

      Pages: 187-192

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2006-07-11  

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