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Analysis of molecular targeting radiosensitization using DPYD depletion

Research Project

Project/Area Number 22791207
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Radiation science
Research InstitutionSapporo Medical University

Principal Investigator

SOMEYA Masanori  札幌医科大学, 医学部, 講師 (60404711)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords放射線治療生物学 / 放射線増感剤 / 放射線
Research Abstract

Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase(DPYD), partially inhibits homologous recombination(HR) repair and has a radiosensitizing effect. We investigated the mechanisms of sensitization of radiation by DPYD inhibition using DLD-1 cells treated with siRNA for DPYD. DPYD depletion by siRNA significantly restrained the formation of radiation-induced foci of Rad51 and RPA, whereas it increased the number of foci of NBS1. The numbers of colocalization of NBS1 and RPA foci in DPYD-depleted cells after radiation were significantly smaller than in the control cells. The phosphorylation of RPA by irradiation was partially suppressed in DPYD-depleted cells, suggesting that DPYD depletion may partially inhibit DNA repair with HR by suppressing phosphorylation of RPA.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (10 results)

All 2012 2011 2010

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (4 results)

  • [Journal Article] Effects of Depletion of Dihydropyrimidine Dehydrogenase on Focus Formation and RPA Phosphorylation2012

    • Author(s)
      Masanori Someya, Masaru Takagi, Koh-ichi Sakata, Yoshihisa Matsumoto, Hiroshi Tauchi, Masahiro Kai, Masato HAREYAMA, Masakazu Fukushima
    • Journal Title

      Journal of Radiation Research

      Volume: 53 Issue: 2 Pages: 250-256

    • DOI

      10.1269/jrr.11190

    • NAID

      130001876844

    • ISSN
      0449-3060, 1349-9157
    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of depletion of dihydropyrimidine dehydrogenase on focus formation and RPA phosphorylation2012

    • Author(s)
      Masanori Someya, Masaru Takagi, Koh-ichi Sakata
    • Journal Title

      Journal of Radiation Research

      Volume: (In press)

    • NAID

      130001876844

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The combination of hyperthermia or chemotherapy with gimeracil for effective radiosensitization2011

    • Author(s)
      Masaru Takagi
    • Journal Title

      Strahlentherapie und Onkologie

      Volume: 188 Issue: 3 Pages: 255-261

    • DOI

      10.1007/s00066-011-0043-6

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gimeracil sensitizes cells to radiation via inhibition of homologous recombination2011

    • Author(s)
      Masaru Takagi, Koh-ichi Sakata, Masanori Someya
    • Journal Title

      Radiotherapy and Oncology

      Volume: 96 Issue: 2 Pages: 259-266

    • DOI

      10.1016/j.radonc.2010.05.020

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gimeracil,an inhibitor of dihydropyrimidine dehydrogenase, inhibits the early step in homologous recombination2011

    • Author(s)
      Koh-ichi Sakata
    • Journal Title

      Cancer Sci

      Volume: 102 Issue: 9 Pages: 1712-1716

    • DOI

      10.1111/j.1349-7006.2011.02004.x

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gimeracil sensitizes cells to radiation via inhibition of homologous recombination.2010

    • Author(s)
      Masaru Takagi
    • Journal Title

      Radiotherapy and Oncology

      Volume: 96 Pages: 259-266

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 放射線誘発NBS1, RPAフォーカスの共局在に対するギメラシルの影響2011

    • Author(s)
      染谷正則、坂田耕一、高木克、晴山雅人、田内広、松本義久、福島正和
    • Organizer
      第24回日本放射線腫瘍学会学術大会
    • Place of Presentation
      兵庫県神戸市
    • Year and Date
      2011-11-17
    • Related Report
      2011 Final Research Report
  • [Presentation] 放射線誘発NBS1,RPAフォーカスの共局在に対するギメラシルの影響2011

    • Author(s)
      染谷正則
    • Organizer
      第24回日本放射線腫瘍学会学術大会
    • Place of Presentation
      兵庫県神戸市
    • Related Report
      2011 Annual Research Report
  • [Presentation] Radiosensitizing effects of Gimeracil2010

    • Author(s)
      Masanori Someya, Masaru Takagi, Koh擁chi Sakata, Hiroshi Tauchi, Yoshihisa Matsumoto, Masato Hareyama, Masakazu Fukushima
    • Organizer
      第56回Radiation Research Society
    • Place of Presentation
      アメリカハワイ州
    • Year and Date
      2010-09-25
    • Related Report
      2011 Final Research Report
  • [Presentation] Radiosensitizing effects of Gimeracil2010

    • Author(s)
      Masanori Someya
    • Organizer
      Radiation Research Society
    • Place of Presentation
      アメリカ ハワイ州
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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