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Study of radiosensitizer using a mouse model of brain metastasis

Research Project

Project/Area Number 24890233
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Radiation science
Research InstitutionJuntendo University

Principal Investigator

HIRAI Takahisa  順天堂大学, 医学部, 助教 (30626669)

Project Period (FY) 2012-08-31 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords放射線増感 / γ線 / X線 / 陽子線 / 炭素線 / PARP / PARP阻害剤 / マウス脳転移モデル / ガンマ線
Research Abstract

In this study, we demonstrated the radiosensitization effect of poly(ADP-ribose) polymerase (PARP) inhibitor AZD2281 in cells exposed to proton beam irradiation through affecting the DNA damage response. The results suggest that AZD2281 might offer beneficial clinical effects without increasing the toxic effects of proton therapy like in photon therapy.
Furthermore, we prepared a mouse model of brain metastasis by direct injection of tumor cells into the animal brain to test the effectiveness of radiosensitizing drugs in vivo. However, because of the low tumor implantation rate in this model, we altered our approach to a mouse model, in which tumor cells were subcutaneously administered into the thigh. In this model, AZD2281 treatment enhanced the anti-tumor effect of X-ray irradiation compared to controls.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • Research Products

    (19 results)

All 2014 2013 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (14 results) (of which Invited: 2 results) Remarks (1 results)

  • [Journal Article] Histological and biochemical analysis of DNA damage after BNCT in rat model2014

    • Author(s)
      Mitsuko Masutani, Diaz Baiseitov, Tasuku Itoh, Takahisa Hirai, Kulzhan Berikkhanova, Yasufumi Murakami, Zhaxybay Zhumadilov, Yoshio Imahori, Masaharu Hoshi, Jun Itami
    • Journal Title

      Applied Radiation and Isotopes

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Parg Deficiency Confers Radio- sensitization through Enhanced Cell Death in Mouse ES Cells Exposed to Various Forms of Ionizing Radiation2013

    • Author(s)
      Shirai H, Fujimori H, Gunji A, Maeda D, Hirai T, Poetsch R A, Harada H, Yoshida T, Sasai K, Okayasu R, Masutani M
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 24 Pages: 100-106

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Parg Deficiency Confers Radio-sensitization through Enhanced Cell Death in Mouse ES Cells Exposed to Various Forms of Ionizing Radiation.2013

    • Author(s)
      Shirai H, Fujimori H, Gunji A, Maeda D, Hirai T, Poetsch AR, Harada H, Yoshida T, Sasai K, Okayasu R, Masutani M.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: Epub ahead of print Issue: 1 Pages: 100-106

    • DOI

      10.1016/j.bbrc.2013.04.048

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PARP阻害剤:がん治療における合成致死と増感剤としての役割2013

    • Author(s)
      平井崇久
    • Journal Title

      放射線生物研究

      Volume: 48 Pages: 52-65

    • NAID

      40019645305

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] がんの陽子線治療と重粒子線治療の生物効果の比較と増感剤の検討2014

    • Author(s)
      平井崇久、斎藤総一郎、藤森浩彰、西尾禎治、岡安隆一、藤森亮、笹井啓資、益谷美都子
    • Organizer
      平成25年度放射線医学総合研究所HIMAC共同利用研究成果発表会
    • Place of Presentation
      千葉市
    • Year and Date
      2014-04-22
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] DNA損傷応答阻害剤の重粒子線及び低LET放射線に対する効果増強作用2014

    • Author(s)
      藤森浩彰、平井崇久、佐藤聡、齋藤総一郎、茂木章、原田博美、笹井啓資、岡安隆一、藤森亮、益谷美都子
    • Organizer
      平成25年度放射線医学総合研究所HIMAC共同利用研究成果発表会
    • Place of Presentation
      千葉市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Radiosensitization by PARP inhibitor to proton beam irradiation in cancer cells2013

    • Author(s)
      Takahisa Hirai, Souichiro Saito, Hiroaki Fujimori, Teiji Nishio, Ryuichi Okayasu, Akira Fujimori, Keisuke Sasai, Mitsuko Masutani
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜市
    • Year and Date
      2013-10-05
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] がんの陽子線治療と重粒子線治療の生物効果の比較と増感剤の検討2013

    • Author(s)
      平井崇久、斎藤総一郎、藤森浩彰、西尾禎治、岡安隆一、藤森亮、笹井啓資、益谷美都子
    • Organizer
      平成24年度放射線医学総合研究所HIMAC共同利用研究成果発表会
    • Place of Presentation
      千葉市
    • Year and Date
      2013-04-23
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] DNA損傷応答阻害剤の重粒子線及び低LET放射線に対する効果増強作用2013

    • Author(s)
      平井崇久、藤森浩彰、吉田周平、齋藤総一郎、茂木章、原田博美、笹井啓資、岡安隆一、藤森亮、益谷美都子
    • Organizer
      平成24年度放射線医学総合研究所HIMAC共同利用研究成果発表会
    • Place of Presentation
      千葉市
    • Year and Date
      2013-04-23
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] DNA損傷応答関連の放射線増感剤の研究2013

    • Author(s)
      平井崇久
    • Organizer
      第54回放射線医学研究所重粒子医科学センター研究交流会
    • Place of Presentation
      千葉市
    • Year and Date
      2013-04-04
    • Related Report
      2013 Final Research Report
  • [Presentation] DNA損傷応答関連の放射線増感剤の研究:PARP阻害剤の放射線増感効果2013

    • Author(s)
      平井崇久
    • Organizer
      放射線医学研究所重粒子医科学センター研究交流会
    • Place of Presentation
      千葉市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ホウ素中性子線捕捉反応後に対するがん細胞の応答機構のプロテオーム解析2013

    • Author(s)
      佐藤 聡、伊藤 祐、齋藤総一郎、藤森浩彰、平井崇久、今堀良夫、伊丹 純、村上康文、中村 浩之、鈴木 実、小野公二、増永慎一郎、益谷美都子
    • Organizer
      第10回日本中性子捕捉療法学会学術大会
    • Place of Presentation
      岡山市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Poly(ADP-ribose) formation/metabolism after DNA damage2013

    • Author(s)
      Hiromi Harada, Miyuki Hozumi, Hiroaki Fujimori, Takahisa Hirai, Soichiro Saito, Yasufumi Murakami, Mitsuko Masutani
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜市
    • Related Report
      2013 Annual Research Report
  • [Presentation] PARP阻害剤の低及び高LET放射線増感効果2013

    • Author(s)
      平井崇久
    • Organizer
      第15回癌治療増感研究シンポジウム
    • Place of Presentation
      奈良市
    • Related Report
      2012 Annual Research Report
  • [Presentation] ポリADP-リボシル化経路阻害による重粒子線に対する放射線増感2013

    • Author(s)
      益谷美都子
    • Organizer
      第15回癌治療増感研究シンポジウム
    • Place of Presentation
      奈良市
    • Related Report
      2012 Annual Research Report
  • [Presentation] DNA損傷応答関連の放射線増感剤の研究2013

    • Author(s)
      平井崇久
    • Organizer
      放射線医学研究所重粒子医科学センター研究交流会
    • Place of Presentation
      千葉市
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] がんの陽子線治療と重粒子線治療の生物効果の比較と増感剤の検討2013

    • Author(s)
      平井崇久
    • Organizer
      平成24年度HIMAC共同利用研究成果発表会
    • Place of Presentation
      千葉市
    • Related Report
      2012 Annual Research Report
  • [Presentation] DNA損傷応答阻害剤の重粒子線及び低LET放射線に対する効果増強作用2013

    • Author(s)
      益谷美都子
    • Organizer
      平成24年度HIMAC共同利用研究成果発表会
    • Place of Presentation
      千葉市
    • Related Report
      2012 Annual Research Report
  • [Remarks] 順天堂大学 研究者情報データベース

    • URL

      https://www.juntendo.ac.jp/graduate/kenkyudb/search/researcher.php?MID=4971

    • Related Report
      2013 Annual Research Report

URL: 

Published: 2012-11-27   Modified: 2019-07-29  

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