Studies about gimeracil, a radiosensitizer

• Project/Area Number: 21591616
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: Sapporo Medical University
• Principal Investigator: SAKATA Koh-ichi 札幌医科大学, 医学部, 准教授 (10235153)
• Co-Investigator(Kenkyū-buntansha): 高木 克 札幌医科大学, 医学部, 研究員 (10404716)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 放射線治療 / 放射線増感 / DNA2重鎖切断 / 相同組換え修復 / DNA 2重鎖切断

Research Abstract

We studied the radiosensitizing effects of gimeracil, a component of TS-1, an anti-cancer drug. We obtained the following results. Gimeracil had the radiosensitizing effects in all different 10 cells examined. Gimeracil did not influence the cell cycle. Gimeracil partially inhibited the homologous recombination repair(HR) of DNA double strand breaks. dihydropyrimidine dehydrogenase(DPYD) is the target protein for radiosensitization by Gimeracil. The inhibitors of DPYD such as Gimeracil could enhance the efficacy of radiotherapy through partial suppression of HR-mediated DNA repair.

Research Products

• [Journal Article] Effects of depletion of dihydropyrimidine dehydrogenase on focus formation and RPA phosphorylation (2012)
  • Author(s): Someya M, Sakata K, Matsumoto Y, Tauchi H, Kai M, Hareyama M, Fukushima M
  • Journal Title: J Radiat Res Volume: (in press)
  • Peer Reviewed
• [Journal Article] The combination of hyperthermia or chemotherapy with Gimeracil for effective radiosensitization (2012)
  • Author(s): Takagi M, Sakata K, Someya M, Matsumoto Y, Tauchi H, Hareyama M, Fukushima M
  • Journal Title: Strahlenther Onkol Volume: 188 Pages: 255-261
  • Peer Reviewed
• [Journal Article] Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase, inhibits the early step in homologous recombination (2011)
  • Author(s): Sakata K, Someya M, Matsumoto Y, Tauchi H, Kai M, Toyota M, Takagi M, Hareyama M, Fukushima M
  • Journal Title: Cancer Sci Volume: 102(9) Pages: 1712-1716
  • NAID: 10030243264
  • Peer Reviewed
• [Journal Article] The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer (2011)
  • Author(s): Someya M, Sakata K, Matsumoto Y, Kamdar P. R, Kai M, Toyota M, Hareyama M
  • Journal Title: Brit J Cancer Volume: 104(11) Pages: 1724-1729
  • Peer Reviewed
• [Journal Article] Gimeracil,an inhibitor of dihydropyrimidine dehydrogenase, inhibits the early step in homologous recombination (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Gimeracil sensitizes cell to radiation via inhibition of homologous recombination (2010)
  • Author(s): Takagi M, Sakata K, Someya M, Tauchi H, Iijima K, Matsumoto Y, Torigoe T, Takahashi A, Hareyama M, Fukushima M
  • Journal Title: Radiother Oncol Volume: 96 Pages: 259-266
  • 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
  • Peer Reviewed
• [Presentation] DNA 2重鎖切断修復の臨床応用 (2012)
  • Author(s): 坂田耕一
  • Organizer: 茨城大学理学部公開シンポジウム第4回Quantum Medicine研究会
  • Place of Presentation: 水戸(招待講演)
  • Year and Date: 2012-03-04
• [Presentation] ギメラシル放射線増感効果の分子メカニズムの検討 (2011)
  • Author(s): 坂田耕一
  • Organizer: 第24回日本放射線腫瘍学会
  • Place of Presentation: 神戸
  • Year and Date: 2011-11-18
• [Presentation] Mechanisms of radiosensitization by Gimeracil, inhibitor of dihydropyrimidine dehydrogenase (2011)
  • Author(s): 坂田耕一
  • Organizer: American Society for Therapeutic Radiology and Oncology, 53th annual meeting
  • Place of Presentation: Miami Beach, FL USA
• [Presentation] ギメラシル放射線増感効果の分子メカニズムの検討 (2010)
  • Author(s): 坂田耕一
  • Organizer: 日本放射線腫瘍学会
  • Place of Presentation: 東京
  • Year and Date: 2010-11-19
• [Presentation] ギメラシル放射線増感効果の分子メカニズムの検討 (2010)
  • Author(s): 坂田耕一
  • Organizer: 第23回日本放射線腫瘍学会
  • Place of Presentation: 東京
  • Year and Date: 2010-09-17
• [Presentation] ギメラシルの放射線増感作用 (2010)
  • Author(s): 坂田耕一
  • Organizer: 第40回日本放射線腫瘍学会制癌シンポジウム
  • Place of Presentation: 札幌
  • Year and Date: 2010-09-17
• [Presentation] ギメラシルの放射線増感作用 (2010)
  • Author(s): 坂田耕一
  • Organizer: 生物部会
  • Place of Presentation: 札幌
  • Year and Date: 2010-07-10
• [Presentation] ギメラシル放射線増感効果の分子メカニズムの検討 (2009)
  • Author(s): 坂田耕一
  • Organizer: 第22回日本放射線腫瘍学会
  • Place of Presentation: 京都
  • Year and Date: 2009-09-17