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Assessment of immune-activated BID gene-radiation combined modality therapy

Research Project

Project/Area Number 23791456
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Radiation science
Research InstitutionKansai Medical University

Principal Investigator

TSUNO Takaya  関西医科大学, 医学部, 助教 (60598259)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsBID / アポトーシス / 分子標的療法 / 遺伝子治療 / IFN-α / 放射線治療
Research Abstract

To overcome difficulties in cancer therapy, we have reported an in vitro study that interferon (IFN)-alpha induces mitochondrial apoptosis mediated by BH3-interacting domain death agonist (BID) in A549 human lung epithelial carcinoma cells resistant to both IFN-alpha and irradiation (Tsuno T, et al, 2012). Here, we further assessed in vivo antitumor effects of IFN-alpha-activated BID gene therapy combined with radiation therapy. In BID gene transfected A549 xenografts inoculated subcutaneously into nude mice, IFN-alpha injection followed by irradiation remarkably inhibited tumor growth. Immunohistochemistry revealed that the combined therapy led to dramatic reduction in BID protein in the nuclei of tumor cells. Electron micrographs disclosed mitochondrial apoptosis induced by the combined therapy. Thus, the combined modality therapy exhibited notable antitumor effects, suggesting that it may be promising to treat malignant tumors even resistant to both IFN-alpha and irradiation.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (9 results)

All 2013 2012 2011 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (6 results)

  • [Journal Article] BID is a critical factor controlling cell viability regulated by IFN-α2012

    • Author(s)
      Tsuno T, Mejido J, Zhao T.
    • Journal Title

      Phillips T, Myers TG, Bekisz J, Zoon KC. J Immunother

      Volume: 35 Issue: 1 Pages: 23-31

    • DOI

      10.1097/cji.0b013e3182372dcf

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] BID is a critical factor controlling cell viability regulated by IFN-α2012

    • Author(s)
      Takaya Tsuno, Josef Mejido, Tongmao Zhao, Terry Phillips, Timothy G. Myers, Joseph Bekisz, Kathryn C. Zoon
    • Journal Title

      Journal of Immunotherapy

      Volume: 35 Pages: 23-31

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel role for IFN-stimulated gene factor 3II in IFN-γsignaling and induction of antiviral activity in human cells2011

    • Author(s)
      Morrow AN, Schmeisser H, Tsuno T, Zoon KC.
    • Journal Title

      J Immunol

      Volume: 186 Issue: 3 Pages: 1685-1693

    • DOI

      10.4049/jimmunol.1001359

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] BH3 INTERACTING DOMAIN DEATH AGONIST GENE THERAPY ENHANCES ANTITUMOR EFFECT OF INTERFERON-ΑLPHA2013

    • Author(s)
      津野隆哉
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートピアアイランド(神戸市)
    • Year and Date
      2013-12-05
    • Related Report
      2013 Final Research Report
  • [Presentation] BH3 INTERACTING DOMAIN DEATH AGONIST GENE THERAPY ENHANCES ANTITUMOR EFFECT OF INTERFERON-ΑLPHA2013

    • Author(s)
      Takaya Tsuno
    • Organizer
      Cytokines 2013
    • Place of Presentation
      Hyatt Regency San Francisco (San Francisco, CA, USA)
    • Year and Date
      2013-10-02
    • Related Report
      2013 Final Research Report
  • [Presentation] What is a critical factor controlling cell viability regulated by IFN-α?2011

    • Author(s)
      津野隆哉
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2011-12-16
    • Related Report
      2013 Final Research Report
  • [Presentation] What is a critical factor controlling cell viability regulated by IFN-α?2011

    • Author(s)
      津野 隆哉
    • Organizer
      第34回 日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Related Report
      2011 Research-status Report
  • [Presentation] BH3 INTERACTING DOMAIN DEATH AGONIST GENE THERAPY ENHANCES ANTITUMOR EFFECT OF INTERFERON-ALPHA

    • Author(s)
      Takaya Tsuno
    • Organizer
      Cytokines 2013
    • Place of Presentation
      Hyatt Regency San Francisco (San Francisco, CA, USA)
    • Related Report
      2013 Annual Research Report
  • [Presentation] BH3 INTERACTING DOMAIN DEATH AGONIST GENE THERAPY ENHANCES ANTITUMOR EFFECT OF INTERFERON-ΑLPHA

    • Author(s)
      津野 隆哉
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートピアアイランド(神戸市)
    • Related Report
      2013 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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