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Inhibition of iNOS activity enhances the anti-tumor effects of alpha-galactosylceramide in cancer model

Research Project

Project/Area Number 25460679
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory medicine
Research InstitutionGifu University

Principal Investigator

Ito Hiroyasu  岐阜大学, 医学(系)研究科(研究院), 准教授 (80373075)

Co-Investigator(Kenkyū-buntansha) SEISHIMA Mitsuru  岐阜大学, 大学院医学系研究科, 教授 (10171315)
SHIRAKAMI Yohei  岐阜大学, 大学院医学系研究科, 助教 (50632816)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsNKT細胞 / 腫瘍免疫 / 一酸化窒素 / 免疫抑制因子 / NKT細胞 / 癌転移 / インドールアミン酸素添加酵素 / 癌免疫療法 / 癌進展
Outline of Final Research Achievements

Alpha-garactosylceramide (GalCer) has anti-tumor effect in the basic research and clinical studies. However, anti-tumor effect of GalCer is limited. GalCer increases the production of IFN-γ which is involved in the suppression of tumor growth. On the other hand, the enhancement of IFN-γ production increases immunosuppressive factors such as nitric oxide (NO). This suppressive action might impair the anti-tumor effect. In the present study, we evaluated the anti-tumor effect of GalCer in the absence of inducible nitric oxide synthase (iNOS). In lung metastatic model, the number of tumor nodules in the lung of iNOS-KO mice treated with GalCer was significantly reduced compared with that in WT mice. The subcutaneous tumor experiments revealed that the administration of GalCer in the absence of iNOS expression enhanced the induction of tumor antigen-specific Th1 response. Our results indicated that the inhibition of iNOS expression could enhance the therapeutic efficacy of GalCer.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (7 results)

All 2015 2013

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 2 results,  Open Access: 1 results) Presentation (3 results)

  • [Journal Article] Inhibition of indoleamine 2,3-dioxygenase activity enhances the anti-tumour effects of a Toll-like receptor 7 agonist in an established cancer model.2015

    • Author(s)
      Ito H, Ando T, Arioka Y, Saito K, Seishima M.
    • Journal Title

      Immunology

      Volume: 144(4) Issue: 4 Pages: 621-630

    • DOI

      10.1111/imm.12413

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combination therapy with α-galactosylceramide and a Toll-like receptor agonist exerts an augmented suppressive effect on lung tumor metastasis in a mouse model.2015

    • Author(s)
      Ando T, Ito H, Arioka Y, Ogiso H, Seishima M.
    • Journal Title

      Oncology Reports

      Volume: 33 Issue: 2 Pages: 826-832

    • DOI

      10.3892/or.2014.3634

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Inhibition of induced nitric oxide synthase enhances the anti-tumor effects on cancer immunotherapy using TLR7 agonist in mice.2015

    • Author(s)
      Ito H, Ando T, Ogiso H, Arioka Y, Seishima M.
    • Journal Title

      Cancer Immunol Immunother.

      Volume: 64(4) Issue: 4 Pages: 429-436

    • DOI

      10.1007/s00262-014-1644-6

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of iNOS activity enhances the anti-tumor effects of alpha-galactosylceramide in established murine cancer model.2015

    • Author(s)
      Ito H, Ando T, Seishima M.
    • Journal Title

      Oncotarget.

      Volume: 6(39) Issue: 39 Pages: 41863-41874

    • DOI

      10.18632/oncotarget.6172

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Toll様受容体アゴニストと一酸化窒素合成酵素の抑制を用いた抗腫瘍効果の検討2015

    • Author(s)
      伊藤弘康、安藤達也、小木曽英介、清島 満
    • Organizer
      第62回日本臨床検査医学会学術集会
    • Place of Presentation
      岐阜市
    • Year and Date
      2015-11-20
    • Related Report
      2015 Annual Research Report
  • [Presentation] Toll様受容体アゴニストとインドールアミン酸素添加酵素制御を用いた抗腫瘍効果の検討2013

    • Author(s)
      伊藤 弘康
    • Organizer
      第53回日本臨床化学会
    • Place of Presentation
      徳島
    • Related Report
      2013 Research-status Report
  • [Presentation] TLR7アゴニストとインドールアミン酸素添加酵素発現抑制による 抗腫瘍効果の検討2013

    • Author(s)
      安藤 達也
    • Organizer
      第35回トリプトファン研究会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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