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The development of brand new therapy for therapy resistant lung disease (interstitial pneumonia and emphysema)

Research Project

Project/Area Number 16590769
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionKurume University

Principal Investigator

YUGE Kentaro  Kurume University, School of medicine, Assistant professor, 医学部, 助手 (00258485)

Co-Investigator(Kenkyū-buntansha) AIZAWA Hisamichi  Kurume University, School of medicine, Professor, 医学部, 教授 (90175711)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsEmphysema / Interstitial Pneumonia / adenovirus / HGF / HB-EGF / TGF-β / Stem Cell Transplantation / IL-18 / 慢性閉塞性肺疾患 / トランスジェニック / サイトカイン
Research Abstract

The development of brand new therapy for therapy resistant lung disease (interstitial pneumonia and emphysema)
I.The trial of the therapy of interstitial pneumonia by gene transduction of adenovirus vector with HGF, HB-EGF and the fusion of extracellular domain of TGF-β receptor II and human IgG Fc portion gene.
1.The trial of the therapy of interstitial pneumonia by gene transduction of adenovirus vector with TGF-β receptor II and human IgG Fc portion gene (Ad.CAG.TGF-β RII/IgG Fc). The TGF-β receptor II and human IgG Fc portion fusion protein which was expressed by Ad.CAG.TGF-β RII/IgG Fc infected 293 cells suppressed the effect of TGF-β. In preparative study, the therapeutic effects were seen in interstitial pneumonia model mouse by transduction of Ad.CAG.TGF-β RII/IgG Fc. It will be the effective therapy if the duration of the protein expression and the immunogenicity of adenovirus are solved.
II.The trials of emphysema by gene trunsduction of HGF, HB-EGF and mesenchymal stem cells.
The trial of the therapy of emphysema by gene transduction of adenovirus vector with human HGF gene (Ad.CAG.HGF).
The obvious improvement was seen in mouse emphysema models by Ad.CAG.HGF injected to hind limbs in contrast to that in Ad.CMV.LacZ injected mouse models. The alveolar structure was more conserved in Ad.CAG.HGF injected group than in Ad.CMV.LacZ injected group. The decrease of tunnel positive cells was seen in Ad.CAG.HGF injected group, so we thought that HGF suppresses the apoptosis of alveolar cells in emphysema as the mechanism of improvement effect of HGF. The cell growth effect and angiogenic effect were also recognized in Ad.CAG.HGF injected group compared with Ad.CMV.LacZ injected group, though statistical differences were not seen.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (12 results)

All 2005 2004 Other

All Journal Article (12 results)

  • [Journal Article] In vivo hepatic HB-EGF gene transduction inhibits Fas-induced liver injury andinduces liver regeneration in mice : A comparative study to HGF.2005

    • Author(s)
      Khai NC, Takahashi T, Ushikoshi H, Nagano S, Yuge K et al.
    • Journal Title

      J. Hepatol. 44・6

      Pages: 1046-1054

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Adenoviral gene transduction of hepatocyte growth factor elicits inhibitoryeffects for hepatoma.2005

    • Author(s)
      Yuge K, Takahashi T, Nagano S, Terazaki Y et al.
    • Journal Title

      Int J Oncol. 27・1

      Pages: 77-85

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Postinfarction gene therapy against transforming growth factor-beta signal modulates infarct tissue dynamics and attenuates left ventricular remodeling and heart failure.2005

    • Author(s)
      Okada H, Takemura G, Kosai K, Li Y, Takahashi T, et al.
    • Journal Title

      Circulation 111・19

      Pages: 2430-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Local overexpression of HB-EGF exacerbates remodeling following myocardial infarction by activating noncardiomyocytes.2005

    • Author(s)
      Ushikoshi H, Takahashi T, Chen X, Khai NC, Esaki M, et al.
    • Journal Title

      Lab Invest. 85・7

      Pages: 862-73

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Local overexpression of HB-EGF exacerbates remodeling following myocardial infarction by activating moncardiomyocytes.2005

    • Author(s)
      Ushikoshi H, Takahashi T, Chen X, Khai NC, Esaki M, et al.
    • Journal Title

      Lab Invest. 85・7

      Pages: 862-873

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] In vivo hepatic HB-EGF gene transduction inhibits Fas-induced liver injury andinduces liver regeneration in mice: A comparative study to HGF.2005

    • Author(s)
      Khai NC, Takahashi T, Ushikoshi H, Nagano S, Yuge K et al.
    • Journal Title

      J Hepatol (インターネット) E-pub

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Adenoviral gene transduction of hepatocyte growth factor elicits inhibitoryeffects for hepatoma.2005

    • Author(s)
      Yuge K, Takahashi T, Nagano S, Terazaki Y et al.
    • Journal Title

      Int J Oncol 27・1

      Pages: 77-85

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Postinfarction gene therapy against transforming growth factor-beta signal modulates infarct tissue dynamics and attenuates left ventricular remodeling and heart failure.2005

    • Author(s)
      Okada H, Takemura G, Kosai K, Li Y, Takahashi T, Esaki M, Yuge K et al.
    • Journal Title

      Circulation 111・19

      Pages: 2430-2437

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Local overexpression of HB-EGF exacerbates remodeling following myocardial infarction by activating noncardiomyocytes.2005

    • Author(s)
      Ushikoshi H, Takahashi T, Chen X, Khai NC, Esaki M, Goto K, Takemura G, Maruyama R, Minatoguchi S, Fujiwara T, Nagano S, Yuge K et al.
    • Journal Title

      Lab Invest 85・7

      Pages: 862-873

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Critical roles for the Fas/Fas ligand system in postinfarction ventricular remodeling and heart failure.2004

    • Author(s)
      Li Y, Yuge K, et al.
    • Journal Title

      Circ Res 95

      Pages: 627-636

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gene therapy eradicating distant disseminated micro-metastases by optimal cytokine expression in the primary lesion only : novel concepts for successful cytokine gene therapy.2004

    • Author(s)
      Nagano S, Yuge K, et al.
    • Journal Title

      Int J Oncol. 24

      Pages: 549-558

    • Related Report
      2004 Annual Research Report
  • [Journal Article] In vivo hepatic HB-EGF gene transduction inhibits Fas-induced liver injury andinduces liver regeneration in mice : A comparative study to HGF.

    • Author(s)
      Khai NC, Takahashi T, Ushikoshi H, Nagano S, Yuge K et al.
    • Journal Title

      J Hepatol. 44・6

      Pages: 1046-1054

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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