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Research on the potentiators of HSV-specific thymidine kinase for the purpose of their application to gene therapy and antiviral therapy

Research Project

Project/Area Number 09672276
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 医薬分子機能学
Research InstitutionToyama Medical and Pharmaceutical University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) HAYASHI Toshimitsu  Toyama Medical and Pharmaceutical University, Faculty of Pharmaceutical Sciences, 薬学部, 助教授 (40092796)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsGene therapy / Antiviral activity / Herpes simplex virus / Thymidine Kinase (TK) / TK-expressing cell lines / Acyclovir / Ganciclovir / Synergistic effect / 単純ヘルペスウイルス / TK発現細胞株
Research Abstract

So far, we found three compounds which exerted synergistic antiherpetic activities with acyclovir (ACV) and ganciclovir(GCV). Especially, of these agents, two diterpenoids, scopadulciol (SDC) and ponicidin (PND), potentiated the cell-killing activity of ACV and GCV in herpes simplex virus type 1(HSV-1) thymidine kinase (TK)-expressing cells. We report about these in detail as follows A naturally occuring flavone, 5,6,7-irimethoxyflavone (TMF), isolated from a plant Gallicarpa japonica, was subjected to antiviral assays . The agent exhibited inhibitory effects on HSV- 1 . TMF and ACV were synergic in their anti-HSV activities, During the evaluation of the effect of ponicidin(PND), which was isolated from a plant Rabdosia ternifolia . on the antiviral activities of ACV and GCV, the compound was found to preferentially activate HSV- 1 -specific TK but not cellular kinases. ln cultured human cancer cells transfected with HSV- 1 TK gene, cytotoxicities of ACV and GCV was strongly potentiated by PND.When the stability of the bioactivity of PND in the blood of mice was determined, the substance showed long-lasting effects on the potentiation of antiherpetic and cytotoxic activities of GCV.Another diterpenoid, SDC isolated from Scoparia dulcis, was also demonstrated as a potentiator of antiherpetic and cell-killing activities of ACV and GCV in in vilro experimental models. These data suggest that combined use of PND or SDC with ACV/GCV will be effective for cancer gene therapy because of more rapid and enhanced tumor elimination.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] K.Hayashi, T.Hayashi, H.Otsuka, Y.Takeda: "Antiviral activity of 5,6,7-trimethoxyflavono and its potentiation of antiherpes activity of acyclovir" Journal of Antimicrobial Chemotherapy. 39・6. 821-824 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Hayashi, T.Hayashi, H.D.Sun, Y.Takeda: "Potentiation of ganciclovir toxicity in nerpes simplex virus thymidine kinase/ganciclovir administration system by ponicidin" Cancer Gene Therapy. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Hayashi, K.Hayashi, S.Asano et al.: "Towards Natural Medicine Research in the 21st Century" E lsevier Science Publisher, 9 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kyoko Hayashiet al.: "Antiviral activity of 5,6,7-trimethoxyflavone and its potentiation of the antigerpes activity of acyclovir" Journal of Antimicrobial Chemotherrapy. 39. 821-824 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kyoko Hayashiet al.: "Potentiation of ganciclovir in herpes simplex virus thymidine kinase/ganciclovir administration system by ponicidin" Cancer Gene Therapy. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Toshimitsu Hayashi et al.: Bioactive diterpenoids from a herb, Scoparia dulcis L.Toward Natural Medicine Research in the 21st Century. Elsevier Science B.V., 9 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Hayashi,T.Hayashi,H.Otsuka,Y.Takeda: "Antiviral activity of 5,6,7-trimethoxyflavone and its potentiation of antiherpes activity of acyclovir" Journal of Antimicrobial Chemotherapy. 39・6. 821-824 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Hayashi,T.Hayashi,Sun,H.-D.,Y.Takeda: "Potentiation of ganciclovir toxicity in herpes simplex virus thymidine kinase / ganciclovir administration system by ponicidin" Cancer Gene Therapy. in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hayashi,T.,Hayashi,K.,Asano,S. et al.: "Towards Natural Medicine Research in the 21st Century" Elsevier Science Publisher, (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Hayashi, T.Hayashi, H.Otsuka, Y.Takeda: "Antivioal activity of 5,6,7-trimethoxyflavone and its potentiation of antiherpes activity of acyclorir" Journal of Antimirobial Chemotherapy. 39.6. 821-824 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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