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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] A human neurodevelopmental disease model using human brainstem organoids-Brainstem organoids from human pluripotent stem cells2020

    • Author(s)
      Eura N, Matsui TK, ....Kuniyasu H, Nagamori S, Muotri AR, Shin JW, Sugie K, Mori E
    • Journal Title

      Front Neurosci

      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

      J Biol Chem.

      Volume: 295 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

    • 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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