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Development of new treatments against malignant bone and soft tissue tumors by using bisphosphonate and ionizing radiation

Research Project

Project/Area Number 23592196
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

MURATA Hiroaki  京都府立医科大学, 医学(系)研究科(研究院), 客員講師 (90360031)

Co-Investigator(Kenkyū-buntansha) KOTO Kazutaka  明治国際医療大学, 公私立大学の部局等, 講師 (50649340)
Co-Investigator(Renkei-kenkyūsha) MAEKAWA Taira  京都大学, 大学院医学研究科, 教授 (80229286)
KIMURA Shinya  佐賀大学, 医学部, 教授 (80359794)
ASHIHARA Eishi  京都薬科大学, 薬学部, 教授 (70275197)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsビスホスフォネート / 軟部肉腫 / 放射線治療 / アポトーシス / 骨肉腫 / ビスホスホネート
Research Abstract

Fibrosarcoma cells were treated with third-generation bisphosphonate (BPs) and/or ionizing radiation (IR), together or sequentially, and the antitumor effects were assessed. BPs significantly enhanced IR-induced apoptosis, especially when cells were treated with BPs followed by IR. We therefore assessed the detailed mechanism of sequential treatment with BPs and IR. Cells in G2 and M phases, the most radiosensitive phases of the cell cycle, were not increased by low concentrations of BPs. However, the levels of expression of Akt, ERK1/2, and NF- B proteins, all of which are related to radioadaptive resistance, were increased within a short time after irradiation with 3 Gy, and this expression was inhibited by a low concentration of BPs, which blocked the prenylation of small GTPases. This sequential treatment also increased the generation of reactive oxygen species (ROS).

Report

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

    (10 results)

All 2013 2012 2011 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (9 results)

  • [Journal Article] Zoledronic acid significantly enhances radiation induced apoptosis against human fibrosarcoma cells by inhibiting radioadaptive signaling.2013

    • Author(s)
      8. Koto K, Murata H, Kimura S, Sawai Y, Horie N, Matsui T, Ryu K, Ashihara E, Maekawa T, Kubo T, Fushiki S.
    • Journal Title

      Int J Oncol

      Volume: 42 Issue: 2 Pages: 525-534

    • DOI

      10.3892/ijo.2012.1735

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Presentation] The third-generation bisphosphonate shows combined effects with anti-tumor drugs in human fibrosarcoma cells2013

    • Author(s)
      Murata H, Koto K, Sawai Y, Matsui TA, Horie N, Fushiki S, Kimura S, Maekawa T, Horii M, Kubo T
    • Organizer
      International Society of Limb Salvage 17th General Meeting
    • Place of Presentation
      Bologna, Italy
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Zoledronic acid significantly enhances radiation-induced apoptosis against human fibrosarcoma cells by inhibiting radioadaptive signaling2013

    • Author(s)
      Koto K, Murata H, Matsui TA, Horie N, Sawai Y, Ashihara E, Kimura S, Maekawa T, Fushiki S, Horii M, Kubo T
    • Organizer
      International Society of Limb Salvage 17th General Meeting
    • Place of Presentation
      Bologna, Italy
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Combined effects of the Third-Generation Bisphosphonate and Radiation on Fibrosarcoma Cells2012

    • Author(s)
      Koto K, Murata H, Sakabe T, Matsui TA, Horie N, Sawai Y, Ashihara E, Kimura S, Maekawa T, Fushiki S, Kubo T
    • Organizer
      13th EFORT Congress
    • Place of Presentation
      Berlin, Germany
    • Year and Date
      2012-05-25
    • Related Report
      2013 Final Research Report
  • [Presentation] 線維肉腫細胞株に対するゾレドロン酸と放射線の併用による細胞内シグナル伝達経路への影響の検討2012

    • Author(s)
      小藤和孝,堀井基行,村田博昭,松井隆明,堀江直行,澤井泰志,久保俊一
    • Organizer
      第27回日本整形外科学会基礎学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] 線維肉細胞株に対するゾレドロン酸と放射線の併用によるアポトーシス誘導効果および細胞内シグナル伝達経路への影響の検討2011

    • Author(s)
      小藤和孝,村田博昭,坂部智哉,大島康史,松井隆明,堀江直行,澤井泰志,久保俊一
    • Organizer
      第26回日本整形外科学会基礎学術集会
    • Place of Presentation
      前橋
    • Year and Date
      2011-10-21
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] 線維肉細胞株に対する第3世代ビスフォスフォネートと放射線の併用による抗腫瘍効果の検討2011

    • Author(s)
      小藤和孝,村田博昭,坂部智哉,松井隆明,堀江直行,澤井泰志,久保俊一
    • Organizer
      第44回日本整形外科学会骨・軟部腫瘍学術集会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] 線維肉腫細胞株に対する第3世代ビスフォスフォネートと放射線の併用による抗腫瘍効果の検討2011

    • Author(s)
      小藤和孝,村田博昭,坂部智哉,松井隆明,堀江直行,澤井泰志,久保俊一
    • Organizer
      第44回日本整形外科学会骨・軟部腫瘍学会
    • Place of Presentation
      京都
    • Related Report
      2011 Research-status Report
  • [Presentation] Combined effects of the Third-Generation Bisphosphonate and Radiation on Fibrosarcoma Cells

    • Author(s)
      Koto K, Murata H, Sakabe T, Matsui TA, Horie N, Sawai Y, Ashihara E, Kimura S, Maekawa T, Fushiki S, Kubo T.
    • Organizer
      13th EFORT Congress 2012
    • Place of Presentation
      Berlin, Germany
    • Related Report
      2012 Research-status Report
  • [Presentation] 線維肉腫細胞株に対するゾレドロン酸と放射線の併用による細胞内シグナル伝達経路への影響の検討

    • Author(s)
      小藤和孝,堀井基行,村田博昭,松井隆明,堀江直行, 澤井泰志,久保俊一
    • Organizer
      第27回日本整形外科学会基礎学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report

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

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