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Efficacy of combination of high-LET radiation and anti-VEGF antibody for glioma stem cell control

Research Project

Project/Area Number 18H02770
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

Hasegawa Masatoshi  奈良県立医科大学, 医学部, 教授 (50251111)

Co-Investigator(Kenkyū-buntansha) 小此木 範之  国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 重粒子線治療研究部, 医長(定常) (00750572)
大野 達也  群馬大学, 大学院医学系研究科, 教授 (10344061)
若月 優  国立研究開発法人量子科学技術研究開発機構, QST病院 治療診断部, 部長 (40399449)
三浦 幸子  奈良県立医科大学, 医学部, 講師 (60597095)
森 英一朗  奈良県立医科大学, 医学部, 准教授 (70803659)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2021: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2020: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Keywordshigh-LET / anti-VEGF antibody / glioma stem cell / carbon ion / proton / RBE / 高LET放射線 / 炭素イオン線 / 抗VEGF抗体 / 陽子線 / 神経膠腫 / 幹細胞 / グリオーマ幹細胞 / p53 / オーガノイド
Outline of Final Research Achievements

To evaluate the efficacy of the combination of high-LET carbon ion beams and anti-VEGF antibody for high grade gliomas, an ependymoblastoma with wild-type p53 was transplanted to nude mice subcutaneously. Tumors were treated with 1) 2Gy carbon ion. 2) 2Gy X-ray, 3) anti-VEGF antibody (bevacizumab 20mg/kg or 40mg/kg), 4) combination of 2Gy carbon ion beams and bevacizumab, or 5) combination of 2Gy X-ray and bevacizumab. Tumor growth delay and gene expression was evaluated 6 or 48 hours after the treatment.
A giloma cell line (U-251) was utilized to evaluate the RBE of proton beams and effect of ultra-high dose rate proton beam irradiation.

Academic Significance and Societal Importance of the Research Achievements

膠芽腫等の悪性神経膠腫は、手術後に、放射線治療(X線)とアルキル化剤(テモゾロミド)を併用するが、予後は不良である。近年、分子標的治療薬の抗VEGF抗体(ベバシズマブ)の併用もしばしば行われているが、その有効性、使用意義等の議論が多い。本研究は悪性神経膠腫に対する低LETのX線、低LETの粒子施である陽子線、高LETの粒子線である炭素イオン線の比較、さらに抗VEGF抗体とX線、重粒子線との併用を検討した研究で、分子標的治療と高LETの粒子線治療を併用する意義についても検討を行ったことが、今後の基礎的、臨床的研究の発展に貢献する可能性がある。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (4 results)

All 2020 2019

All Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (1 results)

  • [Journal Article] Brainstem organoids from human pluripotent stem cells2020

    • Author(s)
      Nobuyuki Eura, Takeshi K. Matsui, Joachim Luginbuhl, Masaya Matsubayashi, Hitoki Nanaura, Tomo Shiota, Kaoru Kinugawa, Naohiko Iguchi, Takao Kiriyama, Canbin Zheng, Tsukasa Kouno, Yan Jun Lan, Pornparn Kongpracha, Pattama Wiriyasermkul, Yoshihiko M. Sakaguchi, Riko Nagata, Tomoya Komeda, Naritaka Morikawa, et al.
    • Journal Title

      Frontiers in Neuroscience

      Volume: - Pages: 00538-00538

    • DOI

      10.3389/fnins.2020.00538

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
  • [Journal Article] 27‐Hydroxycholesterol regulates human SLC22A12 gene expression through estrogen receptor action2020

    • Author(s)
      Matsubayashi M、Sakaguchi YM.、Sahara Y、Nanaura H、Kikuchi S、Asghari A、Bui L、Kobashigawa S、Nakanishi M、Nagata R、Matsui TK.、Kashino G、Hasegawa M、Takasawa S、Eriguchi M、Tsuruya K、Nagamori S、Sugie K、Nakagawa T、Takasato M、Umetani M、Mori E
    • Journal Title

      The FASEB Journal

      Volume: 35 Issue: 1

    • DOI

      10.1096/fj.202002077r

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 悪性神経膠腫を標的とした重粒子線と抗VEGF抗体併用の有効性2019

    • Author(s)
      長谷川正俊
    • Organizer
      放射線医学総合研究所 平成30年度HIMAC共同利用研究成果発表会
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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