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

2001 Fiscal Year Final Research Report Summary

Enhancement of anticancer effects by HSV-TK potentiators and evaluation of navel liposome vectors in MSV-TK/prodding gene therapy

Research Project

Project/Area Number 12672210
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionTOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY

Principal Investigator

HAYASHI Kyoko  Toyama Medical and Pharmaceutical university, Faculty of Medicine Assistant Professor, 医学部, 助手 (60110623)

Co-Investigator(Kenkyū-buntansha) MAITANI Yoshie  Hoshi University, Faculty of pharmaceutical Sciences Professor, 薬学部, 教授 (10231581)
HAYASHI Toshimitsu  Toyama Medical and Pharmaceutical university, Faculty of Pharmaceutical Sciences Professor, 薬学部, 教授 (40092796)
Project Period (FY) 2000 – 2001
Keywordscancer gene therapy / herpes simplex virus / thymidine kinase / acyclovir / ganciclovir / ponicidin / scepadulciol / liposome vector
Research Abstract

In cancer gene therapy trials, herpes simplex virus-specific thymidine kinase (HSV-TK) has been used as a suicide gene in the presence of ganciclovir (GCV) or acyclovir (ACV). Two diterpenoids, scopadulciol (SDC) and ponicidin (PND), stimulated selectively the HSV-TK enzymatic activity. Thus, we studied the potentiation of GCV/ACV toxicity by these compounds in HSV-TK-expressing cancer cells. The results obtained were as follows:
1) Transfectants: Human cancer cells were transfected with the plasmid containing HSV-l tk gene. After cloning, stably HSV-TK-expressing (TK^+) cell clones were obtained. These transfectants showed the ability of forming tumors in nude mice.
2) In vivo anticancer effects: The in vivo growth of TK^+ cells was significantly inhibited by coadministration of SDC/PND and ACV, or of SDC/PND and GCV, compared with single administration of ACV or GCV in spite of lower doses.
3) Bystander effects: The abilities of SDC and PND to potentiate the bystander effects of the products were determined in both in vitro and in vivo systems. In vitro combined use of SDC/PND. With ACV/GCV rendered tumor cells more sensitive to the prodrugs as compared with the prodrug only in 1 to 20% of TK^+ cells. In the in vivo experiments using nude mice injected with 3 or 10% TK^+ cells, significant reduction in tumor volume was observed in mice treated with drug combinations as compared with those treated with the produg only.
4) Toxicity and efficacy: No toxicity of both SDC and PND was seen in mice even at a dose 10-fold higher than that used in the in vivo experiments. SDC has more potent effects than PND, and the possibility for stable supply from organ cultures of the plant.
5) Evaluation of the efficiency of liposome vectors: Transfection efficiency of the gene by cationic liposome was increased in the presence of soybean-derived sterylglucoside. The liver targeting was also improved by this liposome.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] K.Hayashi, T.Hayashi, H.D.Sun, Y.Takeda: "Potentiation of ganciclovir in herpes simplex virus thymidine Kinase/ganciclovir adminstration system by ponicidin"Cancer Gene Therapy. 7. 45-52 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.H.Hwang, K.Hayashi, K.Takayama, Y.Maitani: "Liver-targeted gene transfer into a human hepatoblastoma cell line and in vivo by sterylglucoside-containing cationic liposoma"Gene Therapy. 8. 1276-1280 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Hayashi, T.Hayashi, H.D.Sun, Y.Takeda: "Contribution of a combination of ponicidin and acyclovir/ganciclovir to the antitumor efficacy of the herpes simplex virus thymidine kinase gane therapy system"Human Gene Therapy. 13. 415-423 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Hayashi, T.Hayashi: "Recent Development in chemical and Pharmaceutical Sciences"Transworld Research Network(in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Hayashi, T. Hayashi, H.-D. Sun, and Y. Takeda: "Potentiation of ganciclovir toxicity in the herpes simplex virus thymidine kinase/ganciclovir administration system by ponicidin"Cancer Gene Therapy. 7. 45-52 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.H. Hwang, K. Hayashi, K. Takayama, and Y.Mitani: "Liver-targeted transfer into a human hepatoblastoma cell line and in vivo by sterylglucoside-containing cationic liposomes"Gene Therapy. 8. 1276-1280 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Hayashi, T. Hayashi, H.-D. Sun, and Y. Takeda: "Contribution of a combination of ponicidin and acyclovir/ganciclovir to the antitumor efficacy in HSV-TK gene therapy system"Human Gene Therapy. 13. 415-423 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Hayashi, and T. Hayashi: Bioactive diterpenoids: "from antiviral therapy through gene therapy"Recent Development in Chemical and Pharmaceutical Scinces, Transworld Research Network. Vol.1(in press.).

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

URL: 

Published: 2003-09-17  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi