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Administration of a hypoxic cell sensitizer, 6-FP, enhance of radiation-induced apoptosis in human carcinoma

Research Project

Project/Area Number 21591619
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionKeio University

Principal Investigator

SHIGEMATSU Naoyuki  慶應義塾大学, 医学部, 教授 (30178868)

Co-Investigator(Kenkyū-buntansha) KAWATA Tetsuya  慶應義塾大学, 医学部, 講師 (60234077)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords放射線抵抗性 / 低酸素細胞 / ラジカル / 増感効果 / 染色体解析 / 増感遺伝子解析 / 増感剤
Research Abstract

Hypoxia governs cellular adaption to oxygen deficiency by regulating tumor-relevant genes involved in energy metabolism, angiogenesis, cell proliferation and apoptosis. Heterogeneity of tumor was investigated with respect to radiosensitizing efficiencies of a hypoxic cell sensitizer, 6-FP(6-formylpterin), a metabolite of folic acid. In contrast to apoptosis induced by extracellular H_2O_2, only a few studies have examined apoptosis induced by intracellular H_2O_2. Oxidative stress is known to induce many forms of apoptosis, and as its common mediator, intracellular reactive oxygen species play a cardinal role in oxidative stress-induced apoptosis. Here we used an intracellular H_2O_2 inducer, 6-FP, which is a member of the pterin family. Tumor cells and normal cells were treated with 6-FP before expose of X-ray and then irradiated. We collected the cells and colony efficiency and survival fraction were analyzed. The results showed that the tumor cells were higher colony efficiency than the normal cells, and the cells with both X-ray irradiation and 6-FP treatment were significantly lower survival rate. These results suggested that 6-FP may have radioprotective effect for the tumor cells and the incidated that 6-FP enhances the apoptosis by the radiation-induced and 6-FP may be effective use of the drug.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (2 results)

All 2012

All Journal Article (2 results) (of which Peer Reviewed: 2 results)

  • [Journal Article] Clinical evidence of particle beam therapy2012

    • Author(s)
      Shigematsu N, Shiraishi Y., Seki S., Fukada J., Ohashi T
    • Journal Title

      Int J Clin Oncol

      Volume: 17(2) Pages: 75-78

    • NAID

      10030626272

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impact of MRI-based postimplant dosimetric assessment in prostate brachytherapy using contrast-enhanced T1-weighted images2012

    • Author(s)
      Ohashi T., Momma T., Yamashita S., Nagatusma K., Kanai K., Kitagawa K., Takahashi S., Hanada T., Yorozu A., Shigematsu N
    • Journal Title

      Brachytherapy

      Volume: (In press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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