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Research for a sensitizer of molecular targeted therapy by a regulation of extra-cellular matrix in bone and soft tissue sarcomas

Research Project

Project/Area Number 24791533
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Orthopaedic surgery
Research InstitutionNagoya University

Principal Investigator

URAKAWA Hiroshi  名古屋大学, 医学(系)研究科(研究院), 特任助教 (60584753)

Research Collaborator NISHIDA Yoshihiro  名古屋大学, 医学系研究科, 准教授 (50332698)
KOZAWA Eiji  名古屋大学, 医学部附属病院, 病院助教 (60635572)
IKUTA Kunihiro  名古屋大学, 医学部附属病院, 医員 (40732657)
HAMADA Shunsuke  名古屋大学, 医学部附属病院, 医員 (90747289)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords骨軟部肉腫 / 細胞外マトリックス / ヒアルロン酸
Outline of Final Research Achievements

Hyaluronan (HA) is known to have pivotal roles in the growth, migration and invasion of malignant tumors. We initially investigated the prognostic value of HA in patients with malignant peripheral nerve sheath tumors (MPNST). In multivariate analysis, large tumor size was an independent prognostic factor for overall survival, and HA expression and tumor size were independent prognostic factors for disease-free survival. We also investigated the effects of 4-Methylumbelliferone (MU) on bone and soft tissue sarcoma cell lines. MU treatment inhibited extra-cellular matrix, HA accumulation, cell growth, cell motility, and cell invasiveness. In vivo, administration of MU inhibited the tumor growth in isograft models of Rat chondrosarcoma cells. These data suggest that MU might be a therapeutic candidate for sarcomas via suppression of HA synthesis and accumulation. HA-targeting therapy may have potential as a sensitizer of molecular targeted therapy.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (4 results)

All 2015 2014 2013

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

  • [Journal Article] Hyaluronan expression as a significant prognostic factor in patients with ma lignant peripheral nerve sheath tumors.2014

    • Author(s)
      Ikuta K, Urakawa H, Kozawa E, Arai E, Zhuo L, Futamura N, Hamada S, Kimata K, Ishiguro N, Nishida Y.
    • Journal Title

      Clin Exp Metastasis

      Volume: 31 Issue: 6 Pages: 715-725

    • DOI

      10.1007/s10585-014-9662-5

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Hyaluronan synthesis inhibitor supplements the inhibitory effects of zoledronic acid on bone metastasis of lung cancer2013

    • Author(s)
      Futamura N, Urakawa H, Arai E, Kozawa E, Ishiguro N, Nishida Y
    • Journal Title

      Clin Exp Metastasis

      Volume: 30(5) Issue: 5 Pages: 595-606

    • DOI

      10.1007/s10585-012-9563-4

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒアルロン酸合成制御によるラット軟骨肉腫細胞の抑制効果の検討2015

    • Author(s)
      浜田 俊介、浦川 浩、新井 英介、小澤 英史、生田 国大、篠村 多摩之、 石黒 直樹、西田 佳弘
    • Organizer
      第28回日本軟骨代謝学会
    • Place of Presentation
      東京医科歯科大学(東京都文京区)
    • Year and Date
      2015-03-06 – 2015-03-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] Hyaluronan is a Useful Prognostic Marker and a Possible Therapeutic Target in Patients with MPNSTs2014

    • Author(s)
      Kunihiro Ikuta, Naohisa Futamura, Hiroshi Urakawa, Eisuke Arai, Eiji Kozawa, Shunsuke Hamada, Satoshi Tsukushi, Naoki Ishiguro, Yoshihiro Nishida
    • Organizer
      AAOS 2014 Annual Meeting
    • Place of Presentation
      New Orleans (USA)
    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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