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Suicide gene therapy for gastrointestinal tumors using tumor-specific promoters

Research Project

Project/Area Number 11671298
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionChiba Cancer Center Research Institute

Principal Investigator

TAGAWA Masatoshi  Chiba Cancer Center Research Institute, Division of Pathology, Head, 研究局・病理研究部, 部長 (20171572)

Co-Investigator(Kenkyū-buntansha) OCHIAI Takenori  Chiba University, School of Medicine, Surgery(II), Professor, 医学部・外科学第二講座, 教授 (80114255)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsGene therapy / Promoter / Suicide gene / Transcriptional regulation / c-erbB-2 / Midkine / VEGF / c-erbB2 / エレクトロポレーション / 転写調節 / 消化器がん / レトロウイルス
Research Abstract

Tumor-specific gene expression is important for improved safely and enhanced efficacy of gene therapy for cancer. We then examined promoter regions of the midkine gene which was expressed in tumors but not in normal surrounding tissues or that of the c-erbB-2 and vascular endothelial growth factor gene whose expressions were predominantly found in the tumors of upper gastrointesinal tract and a number of solid tumors, respectively. Our results were as follows. (1)The midkine gene was expressed in 8 out of 14 human esophageal specimens and 14 out of 15 hepatocellular carcinoma specimnens, whereas none of non-tumorous regions of the same patients were negative for the expression. (2)Reporter assays using deletion mutants of the promoter region of the midkine gene showed that the 550-bp fragment was responsible for tumor-specific transcriptional activation. (3)The 250-bp fragment of 5'-upstream region of the c-erbB-2 gene strongly drove the transcription of the fused reporter gene in tumors but not in normal fibroblasts. (4)The 1.2-kb promoter region of the vascular endothelial growth factor gene had a cis-acting element for hypoxic responsiveness. (5)Forced expression of the herpes simplex virus-thymine kinase gene using these linked promoters conferred increased sensitivity of the transfected vells to ganciclovir. (6)The deoxycytidine kinase/ara-C and the uracil phosphoribosyl transferase/5-FU systems were useful for cell killing together with an appropriate promoter.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Miyauchi,M.,Tagawa,M. et al.: "Frequent expression of midkine gene in esophageal cancer suggests a potential usage of its promoter for suicide gene therapy."Jpn J Cancer Res. 90. 469-475 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsubara,H.,Tagawa,M. et al.: "Expression of wild-type p53 gene confers increased sensitivity to radiation and chemotherapeutic agents in human esophageal carcinoma cells"Int J Oncol. 14. 1081-1085 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Maeda,T.,Tagawa,M. et al.: "Loss of tumorigenicity of human breast cancer cells engineered to produce IL-2 IL-4 or GM-CSF in nude mice."Int J Oncol. 15. 943-947 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsubara,H.,Tagawa,M. et al.: "Differential efficacy of suicide gene therapy by herpes simplex virus-thymidine kinase gene reflects the status of p53 gene in human esophageal cancer cells."Anticancer Res. 19. 4157-4160 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tasaki,K.,Tagawa,M. et al.: "Protective immunity is induced in murine colon carcinoma cells by the expression of interleukin-12 or interleukin-18, which activate type 1 helper T cells."Cancer Gene Ther. 7. 247-254 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tasaki,K.,Tagawa,M. et al.: "Transduction of murine colon carcinoma cells with interleukin-15 gene induces antitumor effects in immunocompetent and immunocompromised hosts."Cancer Gene Ther. 7. 255-261 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawamura,K.,Tagawa,M. et al.: "Expression of Escherichia coli uracil phosphoribosyltransferase gene in murine colon carinoma cells augments the antitumoral effect of 5-fluorouracil and induces protective immunity."Cancer Gene Ther. 7. 637-643 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Koshikawa,N.,Tagawa,M. et al.: "Therapeutic efficacy of the suicide gene driven by the promoter of vascular endothelial growth gene against hypoxic tumor cells."Cancer Res. 60. 2936-2941 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawamura,K.,Tagawa,M. et al.: "Transduction of the human deoxycytidine kinase gene in rodent tumor cells induces in vivo growth retardation in syngeneic hosts."Cancer Lett. 156. 151-157 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tasaki,K.,Tagawa,M. et al.: "Expression of herpes simplex virus-thymidine kinase gene controlled by a promoter region of the midkine gene confers selective cytotoxicity to ganciclovir in human carcinoma cells."Int J Cancer. 91. 723-727 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyauchi, M., Shimada, H., Kadomatsu, K., Muramatsu, T., Matsubara, S., Ikematsu, S., Takenaga, K., Asano, T., Ochiai, T., Sakiyama, S.and Tagawa, M.: "Frequent expression of midkine gene in esophageal cancer suggests a potential usage of its promoter for suicide gene therapy."Jpn. J.Cancer Res.. 90. 469-475 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsubara, H., Kimura, M., Sugaya, M., Koide, Y., Gunji, Y., Takegana, K., Asano, A., Ochiai, T., Isono, K., Sakiyama, S.and Tagawa, M.: "Expression of wild-type p53 gene confers increased sensitivity to radiation and chemotherapeutic agents in human esophageal carcinoma cells."Int. J.Oncol. 14. 1081-1085 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Maeda, T., Matsubara, H., Sugaya, M., Miyazawa, Y., Gunji, Y., Ochiai, T., Sakiyama, S.and Tagawa, M.: "Loss of tumorigenicity of human breast cancer cells engineered to produce IL-2, IL-4 or GM-CSF in nude mice."Int. J.Oncol.. 15. 943-947 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsubara, H., Kawamura, K., Sugaya, M., Koide, Y., Gunji, Y., Takenaga, K., Asano, T., Ochiai, T., Sakiyama, S.and Tagawa, M.: "Differential efficacy of suicide gene therapy by herpes simplex virus-thymidine kinase gene reflects the status of p53 gene in human esophageal cancer cells."Anticancer Res.. 19. 4157-4160 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tasaki, K., Yoshida, Y., Maeda, T., Miyauchi, M., Kawamura, K., Takenaga, K., Yamamoto, H., Kouzu, T., Asano, T., Ochiai, T., Sakiyama, S.and Tagawa, M.: "Protective immunity is induced in murine colon carcinoma cells by the expression of interleukin-12 or interleukin-18, which activate type 1 helper T cells."Cancer Gene Ther.. 7. 247-254 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tasaki, K., Yoshida, Y., Miyauchi, M., Maeda, T., Takenaga, K., Kouzu, T., Asano, T., Ochiai, T., Sakiyamna, S.and Tagawa, M.: "Transduction of murine colon carcinoma cells with interleukin-15 gene induces antitumor effects in immunocompetent and immunocompromised hosts."Cancer Gene Ther.. 7. 255-261 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawamura, K., Tasaki, K., Hamada, H., Takenaga, K.Sakiyama, S.and Tagawa, M.: "Expression of Escherichia coli uracil phosphoribosyltransferase gene in murine colon carcinoma cells augments the antitumoral effect of 5-fluorouracil and induces protective immunity."Cancer Gene Ther.. 7. 637-643 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Koshikawa, N., Takenaga, K., Tagawa, M.and Sakiyama, S.: "Therapeutic efficacy of the suicide genedriven by the promoter of vascular endothelial growth gene against hypoxic tumor cells."Cancer Res.. 60. 2936-2941 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawamura, K., Namba, H., Bahar, R., Miyauchi, M., Maeda, T., Hamada, H., Sakiyama, S.and Tagawa, M.: "Transduction of the human deoxycytidinekinase gene in rodent tumor cells induces in vivo growth retardation in syngeneic hosts."Cancer Lett.. 156. 151-157 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Miyauchi, M., Yoshida, Y., Tada, Y., Narita, M., Maeda, T., Bahar, R., Kadomatsu, K., Muramatsu, T., Matsubara, S., Nakagawara, A., Sakiyama, S.and Tagawa, M.: "Expression of herpes simplex virus-thymidine kinase gene controlled by a promoter region of the midkine gene congers selective cytotoxicity to ganciclovir in human carcinoma cells."Int. J.Cancer. 91. 723-727 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tasaki,K.,Ochiai,T. et al: "Protective immunity is induced in murine colon carcinoma cells by the expression of interleukin-12 or interleukin-18, which activate type 1 helper T cells."Cancer Gene Ther. 7. 247-254 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tasaki,K.,Ochiai,T. et al: "Transduction of murine colon carcinoma cells with interleukin-15 gene induces antitumor effects in immunocompetent and immunocompromised hosts."Cancer Gene Ther. 7. 255-261 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshida,Y.,Tagawa,M. et al: "Impaired tumorigenicity of human pancreatic cancer cells retrovirally transduced with interleukin-12 or interleukin-15 gene."Cancer Gene Ther. 7. 324-331 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawamura,K.,Tagawa,M. et al: "Expression of Escherichia coli uracil phosphoribosyltransferase gene in murine colon carcinoma cells augments the antitumoral effect of 5-fluorouracil and induces porotective immunity."Cancer Gene Ther. 7. 637-643 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawamura,K.,Tagawa,M. et al: "Transduction of the human deoxycytidine kinase gene in rodent tumor cells induces in vivo growth retardation in syngeneic hosts."Cancer Lett. 156. 151-157 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyauchi,M.,Tagawa, M. et al: "Expression of herpes simplex virus-thymidine kinase gene controlled by a promoter region of the midkine gene confers selective cytotoxicity to ganciclovir in human carcinoma cells."Int J Cancer. 91. 723-727 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyauchi M.,Tagawa M.et al.: "Frequent expression of midkine gene in esophageal cancer suggests a potential usage of its promoter for suicide gene therapy"Japanese Journal of Cancer Research. 90. 469-475 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshida H.,Tagawa M.et al.: "Induced immunity by the expression of interleukin-2 or granulocyte macrophagecolony stimulating factor gene in murine neuroblastoma cells generated antitumor response for established tumors"Cancer Gene Ther.. 6. 395-401 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsubara H.,Ochiai T.et al.: "Expression of wild-type p53 gene confers increased sensitivity to radiation and chemotherapeutic agents in human esophageal carcinoma cells"Int.J.Oncol.. 14. 1081-1085 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsubara H.,Ochiai T.et al: "Differential efficacy of suicide gene therapy by herpes simplex virus-thymidine kinase gene reflects the status of p53 gene in human esophageal cancer cells"Anticancer Res.. 19. 4157-4160 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tasaki K.,Tagawa M.et al.: "Transduction of murine colon carcinoma cells with interleukin-15 gene induces antitumor effect in immunocompetent and immunocompromised hosts"Cancer Gene Ther.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawamura K.,Tagawa M.et al.: "Expression of Escherichia coli uracil phosphoribosytransferase gene in murine colon carcinoma cells augments the antitumor effect of 5-fluorouracil and induces protective immunity"Cancer Gene Ther.. (in press).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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