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Radiosensitization

Research Project

Project/Area Number 24791293
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Radiation science
Research InstitutionKyoto University

Principal Investigator

YOSHIMURA MICHIO  京都大学, 医学(系)研究科(研究院), 助教 (40597936)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords放射線増感 / 分子標的薬 / 放射線治療 / 細胞周期 / 放射線 / 分子標的 / 放射線増感剤
Outline of Final Research Achievements

Polo-like kinase 1 is a serine/threonine kinase that functions in mitotic progression. We herein investigated whether PLK1 blockade enhanced the cytotoxic effects of radiation by modulating the cell cycle phase of cancer cells using the novel small molecule inhibitor of PLK1, TAK-960. In vitro clonogenic assays as well as time-lapse imaging and flow cytometric analyses of cell cycle phases demonstrated that the TAK-960 treatment exhibited a radiosensitizing effect, especially when it increased the proportion of M-phase cells. Tumor growth delay assay combined with optical imaging of cell cycle phases in tumor xenografts also demonstrated that the radiosensitizing effect of TAK-960 depended on an increase in the proportion of M-phase cells. These results provide a rational basis of targeting PLK1 for radiosensitization when considering the therapeutic time window for M-phase arrest as the best timing for radiation treatment.

Report

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

    (10 results)

All 2015 2014 2013 2012

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (3 results) Book (1 results)

  • [Journal Article] Radiotherapy for patients with isolated local recurrence of primary resected pancreatic cancer : Prolonged disease-free interval associated with favorable prognosis2014

    • Author(s)
      Nakamura, A. Itasaka S, Takaori K, Kawaguchi Y, Shibuya K, Yoshimura M, Matsuo Y, Mizowaki T, Uemoto S, Hiraoka M.
    • Journal Title

      Strahlentherapie und Onkologie

      Volume: MAR 6 Issue: 5 Pages: 485-485

    • DOI

      10.1007/s00066-014-0610-8

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Factors influencing survival outcome for radiotherapy for biliary tract cancer: A multicenter retrospective study2014

    • Author(s)
      Yoshioka, Y. Ogawa K, Yoshimura M et al.
    • Journal Title

      Radiotherapy and oncology

      Volume: Feb 20 Issue: 3 Pages: 2167-2167

    • DOI

      10.1016/j.radonc.2014.01.003

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] HIF-1-mediated metabolic reprogramming reduces ROS levels and facilitates the metastatic colonization of cancers in lungs.2014

    • Author(s)
      1. Zhao T, Zhu Y, Morinibu A, Kobayashi M, Shinomiya K, Itasaka S, Yoshimura M, Guo G, Hiraoka M, Harada H.
    • Journal Title

      Scientific Reports

      Volume: 4.3793 Issue: 1 Pages: 1-7

    • DOI

      10.1038/srep03793

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of decreased hypoxia-inducible factor 1 activity and resultant G(1)-S cell cycle transition in radioresistance of perinecrotic tumor cells2013

    • Author(s)
      Y. Zhu, T. Zhao, S. Itasaka, L. Zeng, C.J. Yeom, K. Hirota, K. Suzuki, A. Morinibu, K. Shinomiya, G. Ou, M. Yoshimura, M. Hiraoka, H. Harada
    • Journal Title

      Oncogene

      Volume: 32 Issue: 16 Pages: 2058-2068

    • DOI

      10.1038/onc.2012.223

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Microenvironment and radiation therapy2013

    • Author(s)
      M Yoshimura, S Itasaka, H Harada,
    • Journal Title

      Biomed Res Int

      Volume: 2013 Pages: 685308-685308

    • DOI

      10.1155/2013/685308

    • NAID

      120005243745

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cancer cells that survive radiation therapy acquire HIF-1 activity and translocate towards tumour blood vessels2012

    • Author(s)
      H. Harada, M. Inoue, S. Itasaka, K. Hirota,A. Morinibu, K. Shinomiya, L. Zeng, G. Ou, Y. Zhu, M. Yoshimura, W.G. McKenna, R.J. Muschel, M. Hiraoka
    • Journal Title

      Nature communications

      Volume: 3 Issue: 1 Pages: 783-783

    • DOI

      10.1038/ncomms1786

    • NAID

      120004007582

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] PLK1 blockade enhances therapeutic effects of radiation by inducing cell cycle arrest at the mitotic phase2015

    • Author(s)
      井上実, 吉村通央, 小林稔, 板坂聡, 本田弘平,原田浩, 平岡真寛
    • Organizer
      第17回癌治療増感研究シンポジウム
    • Place of Presentation
      奈良
    • Year and Date
      2015-02-06 – 2015-02-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] A PLK1 inhibitor, TAK-960, acts as a radiosensitizer by inducing mitotic arrest2014

    • Author(s)
      井上実, 吉村通央, 小林稔, 板坂聡, 本田弘平,原田浩, 平岡真寛
    • Organizer
      日本放射線腫瘍学会第27回学術大会
    • Place of Presentation
      横浜
    • Year and Date
      2014-12-11 – 2014-12-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] A novel small molecule inhibitor of PLK1, TAK-960, sensitizes therapeutic effect of radiation by inducing mitotic arrest2014

    • Author(s)
      井上実, 吉村通央, 小林稔, 板坂聡, 本田弘平,原田浩, 平岡真寛
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Book] Principles of Molecular Diagnostics and Personalized Cancer Medicine2012

    • Author(s)
      Dongfeng Tan, Henry T. Lynch, Yoshimura, M. Harada, H. Hiraoka, M.
    • Total Pages
      992
    • Publisher
      Lippincott Williams & Wilkins
    • Related Report
      2012 Research-status Report

URL: 

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

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