• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Suicide gene therapy for intractable gastrointestinal cancer with tumor specific promoters

Research Project

Project/Area Number 13670580
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

KAWAMURA Kiyoko  Chiba Cancer Center Research Institute Division of Pathology Research Fellow, 病理研究部, 主席研究員 (80260248)

Co-Investigator(Kenkyū-buntansha) SAISHO Hiromitsu  Chiba University, Graduate School of Medicine Department of Medicine and Clinical Oncology Professor, 大学院・医学研究院腫瘍内科学, 教授 (10092058)
TAGAWA Masatoshi  Chiba Cancer Center Research Institute Division of Pathology Head, 病理研究部, 部長 (20171572)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsGene therapy / Tumor promoter / HSV-TK / Reporter assay / c-erbB-2 / Survivin / Midkine / c-erbB-2
Research Abstract

We examined the transcriptional regulatory regions of the midkine gene, which is expressed in a variety of tumors but scarcely in normal cells, with luciferase reporter assays. We demonstrated that the most potent transcriptional activity was obtained with the 2335-bp upstream region tested in hepatocellular carcinoma and with the 609-bp region in pancreatic tumors. The 1041- and the 335-bp but not the 70-bp region contained cis-acting elements for transcriptional activation in both types of tumor cells. Transfection of the herpes simplex virus-thymidine kinase (HSV-TK) gene fused with the midkine regulatory region in tumor cells increased their susceptibility to a prodrug ganciclovir. The regulatory regions of the c-erbB-2 gene, which is highly expressed in breast and gastric cancer, were also analyzed with the same reporter assays. We showed that the activity of the 251-bp region was the strongest in tumors among other genomic fragments deleted from 5'-side. Tumor cells transfected with the 251-bp region linked with the HSV-TK gene was more sensitive to ganciclovir in vitro and in vivo than parent cells. We also investigated the transcriptional control regions of the survivin gene, which is highly expressed in the G2/M phase. Deletion of the regulatory regions from the 5'-side showed that the 500-bp region was responsible for the preferential expression in tumor cells but not in normal cells.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Kawamura K, et al.: "The error-prone DNA polymerase ζ catalytic subunit (Rev3) gene is ubquitously expressed in normal and malignant human tissues"Int.J.Oncol.. 18. 97-103 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawamura K, et al.: "Bystander effect in uracil phophoribosyltransferase/5-fluorouracil-mediated suicide gene therapy is correlated with the level of intercellular communication"Int.J.Oncol.. 18. 117-120 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] O-Wang J, Kawamura K, et al.: "DNA polymerase κ implicated in spontaneous and DNA damage-induced mutagenesis, is overexpressed in lung cancer"Cancer Res.. 61. 5366-5369 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maeda T, Tagawa M, et al.: "A minimum c-erbB-2 promoter-mediated expression of herpes simplex virus thymidine kinase gene confers selective cytotoxicity of human breast cancer cells to ganciclovir"Cancer Gene Ther.. 8. 890-896 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida Y, Tagawa M, et al.: "A promoter region of midkine gene can activate transcription of an exogenous suicide gene in human pancreatic cancer"Anticancer Res.. 22. 117-120 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawamura K, Tagawa T, et al.: "Secretion on interleukin-10 from murine colon carcinoma cells suppresses systemic anti-tumor immunity and impairs protective immunity induced against the tumors"Cancer Gene Ther.. 9. 109-115 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tagawa M, et al.: "Identification of a minimal c-erbB-2 promoter region that mediates preferential expression of a linked foreign gene in human breast cancer cells"Int.J.Oncol.. 20. 607-610 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawamura K, Tagawa M, et al.: "An essential role for REV3 in mammalian cell survival : absence of REV3 induces p53-independent embyronic cells"Biochem.Biophys.Res.Commun.. 293. 1132-1137 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Bahar R, Kawamura K, et al.: "Growth retardation, polyploidy and multinucleation induced by Clast3, a novel cell cycle-regulated protein"J.Biol.Chem.. 277. 40012-40019 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saisho H, et al.: "Expression of the interleukin-21 gene in murine colon carcinoma cells generates systemic immunity in the inoculated hosts"Cancer Gene Ther. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawamura, K., O-Wang, J., Bahar, R., Koshikawa, N., Shishikura, T. Nakagawara, A., Sakiyama, S., Kajiwara, K., Kimura, M. and Tagawa, M.: "The error-prone DNA polymerase ζ catalytic subunit (Rev3) gene is ubiquitously expressed in normal and malignant human tissues"Int. J. Oncol.. 18. 97-103 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawamura, K., Bahar, R., Namba, H., Seimiya, M., Takenaga, K., Hamada, H., Sakiyama, S. and Tagawa, M.: "Bystander effect in uracil phosphoribosyltransferase/5-fluorouracil-mediated suicide gene therapy is correlated with the level of intercellular communication"Int J. Oncol.. 18. 117-120 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] O-Wang, J., Kawamura, K., Tada, Y., Ohmori, H., Kimura, H., Sakiyama, S and Tagawa, M.: "DNA polymerase κ implicated in spontaneous and DNA damage-induced mutagenesis, is overexpressed in lung cancer"Cancer Res.. 61. 5366-5369 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 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 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(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maeda, T., O-Wang, J., Matsubara, H., Asano, T., Ochiai, T., Sakiyama, S. and Tagawa, M.: "A minimum c-erbB-2 promoter-mediated expression of herpes simplex virus thymidine kinase gene confers selective cytotoxicity of human breast cancer cells to ganciclovir"Cancer Gene Ther.. 8. 890-896 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida, Y., Tomizawa, M., Bahar, R., Miyauchi, M., Yamaguchi, T., Saisho, H., Kadomatsu, K., Muramatsu, T., Matsubara, S., Sakiyama, S. and Tagawa, M.: "A promoter region of midkine gene can activate transcription of an exogenous suicide gene in human pancreatic cancer"Anticancer Res.. 22. 117-120 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawamura, K., Bahar, R., Natsume, W., Sakiyama, S. and Tagawa, T.: "Secretion of interleukin-10 from murine colon carcinoma cells suppresses systemic anti-tumor immuinuty and impairs protective immunity induced against the tumors"Cancer Gene Ther.. 9. 109-115 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yu, L., Kamo, S. and Tagawa, M.: "Identification of a minimal c-erbB-2 promoter region that mediates preferential expression of a linked foreign gene in human breast cancer cells"Int. J. Oncol.. 20. 607-610 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] O-Wang, J., Kajiwara, K., Kawamura K., Kimura, M., Miyagishima, H., Kosei, A. and Tagawa, M.: "An essential role for REV3 in mammalian cell survival : absence of REV3 induces p53-independent embryonic cells"Biochem. Biophys. Res. Commun.. 293. 1132-1137 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ba|har, R., O-Wang, J., Kawamura, K., Seimiya, M., Wang, Y., Hatano, M., Okada, S., Tokuhisa, T., Watanabe, T. and Tagawa, M.: "Growth retardation, polyploidy and multinucleation induced by Clast3, a novel cell cycle-regulated protein"J. Biol. Chem.. 277. 40012-40019 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ugai, S., Shimozato, O., Kawamura, K., Wang, Y-Q., Yamaguchi, T., Saisho, H., Sakiyama, S and Tagawa, M.: "Expression of the interleukin-21 gene in murine colon carcinoma cells generates systemic immunity in the inoculated hosts"Cancer Gene Ther.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawamura K, Tagawa T, et al.: "Secretion of interleukin-10 from murine colon carcinoma cells suppresses systemic anti-tumor immunity and impairs protective immunity induced against the tumors"Cancer Gene Ther.. 9. 109-115 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tagawa M, et al.: "Identification of a minimal c-erbB-2 promoter region that mediates preferential expression of a linked foreign gene in human breast cancer cells"Int. J. Oncol.. 20. 607-610 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshida Y, Tagawa M, et al.: "A promoter region of midkine gene can activate transcription of an exogenous suicide gene in human pancreatic cancer"Anticancer Res.. 22. 117-120 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawamura K, Tagawa M, et al.: "An essential role for REV3 in mammalian cell survival : absence of REV3 induces p53-independent embryonic cells"Biochem. Biophys. Res. Commun.. 293. 1132-1137 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Bahar R, Kawamura K, et al.: "Growth retardation, polyploidy and multinucleation induced by Clast3, a novel cell cycle-regulated protein"J. Biol. Chem.. 277. 40012-40019 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Saisho H, et al.: "Expression of the interleukin-21 gene in murine colon carcinoma cells generates systemic immunity in the inoculated hosts"Cancer Gene Ther.. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawamura K, et al.: "The error-prone DNA polymerase ζ catalytic subunit(Rev3)gene is ubiquitously expressed in normal and malignant human tissues"Int. J. Oncol.. 18. 97-103 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawamura K, et al.: "Bystander effect in uracil phosphoribosyltransferase/5-fluorouracil-mediated suicide gene therapy is correlated with thelevel of intercellular communication"Int. J. Oncol.. 18. 117-120 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] O-Wang J, Kawamura K, et al.: "DNA polymerase κ implicated in spontaneous and DNA damage-induced mutagenesis, is overexpressed in lung cancer"Cancer Res.. 61. 5366-5369 (2001)

    • Related Report
      2001 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
      2001 Annual Research Report
  • [Publications] Maeda T, Tagawa M, et al.: "A minimum c-erbB-2 promoter-mediated expression of herpes simplex virus thymidine kinase gene confers selective cytotoxicity of human breast cancer cells to ganciclovir"Cancer Gene Ther.. 8. 890-896 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshida Y, Saisho H, et al.: "A promoter region of midkine gene can activate transcription of an exogenous suicide gene in human pancreatic cancer"Anticancer Res.. (in press).

    • Related Report
      2001 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi