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Basic analysis of secreted factors which suppress delayed ROS for effective radiotherapy

Research Project

Project/Area Number 18K07764
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionNara Medical University

Principal Investigator

Kashino Genro  奈良県立医科大学, 医学部, 准教授 (00437287)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsVEGF / 活性酸素 / 放射線治療 / 細胞老化 / p53 / 酸化ストレス / 放射線抵抗性 / ミトコンドリア / エクソソーム / 放射線感受性 / 遅発性活性酸素 / 細胞外因子 / バイスタンダー効果
Outline of Final Research Achievements

In this study, we searched for cancer cell-specific extracellular factors that affect radiosensitivity. As a result, it was found that in the culture of rat glioma C6 cells, VEGF contained in the culture supernatant for 3 days of culture suppresses mitochondrial ROS via mitochondrial metabolism, leading to radiation resistance. On the other hand, it was found that the glutamic acid depleted state in the culture supernatant showed a radiation sensitizing effect. These results suggest that fluctuations in cytokine secretion levels in culture supernatants and the amount of trophic factors involved in amino acid and glucose metabolism are important target factors for improving therapeutic effects that affect radiosensitivity. ..

Academic Significance and Societal Importance of the Research Achievements

放射線治療による治療効果をより高くするためには、正常細胞とがん細胞の性質を理解し、正常細胞では放射線による障害を抑え、がん細胞では放射線による致死効果が高くなるような工夫が必要である。本研究で、細胞分泌性因子の中でVEGFががん細胞特異的な放射線抵抗性因子である可能性を示すことが出来た。この因子を標的とした放射線治療が有効となる可能性が高い。また栄養因子の影響もがん細胞では現れやすいことがわかった。このような基礎研究の結果が、将来の新しい放射線治療の開発に結びつくことを期待したい。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2020 2019 2018

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Inhibition of the ATR kinase enhances 5-FU sensitivity independently of nonhomologous end-joining and homologous recombination repair pathways2020

    • Author(s)
      Ito Soichiro S.、Nakagawa Yosuke、Matsubayashi Masaya、Sakaguchi Yoshihiko M.、Kobashigawa Shinko、Matsui Takeshi K.、Nanaura Hitoki、Nakanishi Mari、Kitayoshi Fumika、Kikuchi Sotaro、Kajihara Atsuhisa、Tamaki Shigehiro、Sugie Kazuma、Kashino Genro、Takahashi Akihisa、Hasegawa Masatoshi、Mori Eiichiro、Kirita Tadaaki
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 37 Pages: 12946-12961

    • DOI

      10.1074/jbc.ra120.013726

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 放射線感受性を変動させる細胞分泌性因子の解析2019

    • Author(s)
      菓子野元郎、小橋川新子、熊谷純
    • Organizer
      日本放射線影響学会第62回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] グルコピラノシルアスコルビン酸の照射後処理による放射線感受性の変化~正常細胞とがん細胞の比較2018

    • Author(s)
      小橋川新子、菓子野元郎、真田悠生、田野恵三、増永慎一郎
    • Organizer
      日本放射線影響学会第61回大会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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