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Identification of highly densed areas of glioma-stem cells in glioblastoma.

Research Project

Project/Area Number 20K08004
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 InstitutionIwate Medical University

Principal Investigator

Beppu Takaaki  岩手医科大学, 医学部, 教授 (70275543)

Co-Investigator(Kenkyū-buntansha) 寺崎 一典  岩手医科大学, 医歯薬総合研究所, 准教授 (60285632)
藤原 俊朗  岩手医科大学, 薬学部, 講師 (60405842)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords膠芽腫 / PET / 腫瘍幹細胞 / FRP170 / Methionine / glioma stem cell / glioblastoma / 18F-FRP170 / 11C-methionine / glioma-stem cell / CD133
Outline of Research at the Start

グリオーマ幹細胞(glioma stem-like cell, GSC)の存在は膠芽腫の治療耐性に大きく影響していることから、画像によってGCSの高密度領域を視覚化することは有意義である。PET画像における低酸素細胞トレーサ とアミノ酸代謝トレーサ重複して集積する箇所にGSCが高密度に分布している、という仮説を明らかにする研究である。

Outline of Final Research Achievements

The aim of the current study is to clarify whether glioma-stem cells densely exist within glioblastoma tissues showing high-uptakes of both tracers for hypoxic cells (18F-FRP170) and amino-acid metabolic cells (11C-methionine) on positron emission topography (PET). As a result, lesions showing high-uptake of both tracers were depicted on PET in all of 10 patients. Those tissues microscopically included micro-necroses and proliferating micro-vessels. In addition, glioma stem-like cells stained with nestin, CD133, SOX2, musashi-1 were detected in those tissues.

Academic Significance and Societal Importance of the Research Achievements

膠芽腫において18F-FRP170と11C-methionineが重複して集積する箇所は、腫瘍幹細胞の至適箇所とされている低酸素組織と血管近傍組織が近接して混在する組織であり、グリオーマ幹細胞関連蛋白を発現する腫瘍細胞が高密度に存在したことから、同部はグリオーマ幹細胞様腫瘍細胞の高密度領域である可能性が示唆された。
腫瘍幹細胞は放射線治療や薬物治療に抵抗性を有するとされており、18F-FRP170と11C-methionineの2つのトレーサーによるPET画像によって、治療における究極的な標的部位を視覚化できることは今後の膠芽腫治療の一助となる可能性がある。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (18 results)

All 2024 2022 2021 2020 2019

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Glypican-1-targeted antibody?drug conjugate inhibits the growth of glypican-1-positive glioblastoma2024

    • Author(s)
      Uchida Shun、Serada Satoshi、Suzuki Yuji、Funajima Eiji、Kitakami Kei、Dobashi Kazumasa、Tamatani Satomi、Sato Yuichi、Beppu Takaaki、Ogasawara Kuniaki、Naka Testuji
    • Journal Title

      Neoplasia

      Volume: 50 Pages: 100982-100982

    • DOI

      10.1016/j.neo.2024.100982

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Positron emission tomography with 11C-methyl-L-methionine as a predictor of consequential outcomes at the time of discontinuing temozolomide-adjuvant chemotherapy in patients with residual IDH-mutant lower-grade glioma2022

    • Author(s)
      Beppu T, Iwaya T, Sato Y, Nomura J, Terasaki K, Sasaki T, Yamada N, Fujiwara S, Sugai T, Ogasawara K
    • Journal Title

      Clin Nucl Med

      Volume: in press Issue: 7 Pages: 569-574

    • DOI

      10.1097/rlu.0000000000004221

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Utility of arterial spin labeling for objective assessment of intratumoral microvessels in diffuse hemispheric glioma, H3 G34R-mutant: a case report and literature review.2022

    • Author(s)
      Kitakami K, Beppu T, Sato Y, Kurose A, Ogasawara K.
    • Journal Title

      Radiology Case Reports

      Volume: 18 Issue: 3 Pages: 856-861

    • DOI

      10.1016/j.radcr.2022.11.074

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of outcome at the time of discontinuing TMZ-adjuvant therapy in IDH-mutant lower grade glioma using 11C-methinine PET2022

    • Author(s)
      Beppu T, Sato Y, Sasaki T, Terasaki K, Iwaya T, Ogasawara K
    • Journal Title

      Neuro-Oncology Advances

      Volume: 3 Issue: Supplement_6 Pages: vi20-vi20

    • DOI

      10.1093/noajnl/vdab159.075

    • Related Report
      2021 Research-status Report
  • [Journal Article] Clinicopathological risk factors for a poor prognosis of primary central nervous system lymphoma in elderly patients in the Tohoku and Niigata area: a multicenter, retrospective, cohort study of the Tohoku Brain Tumor Study Group2022

    • Author(s)
      Asano K, Yamashita Y, Ono T, Natsumeda M, Beppu T, Matsuda K, Ichikawa M, Kanamori M, Matsuzaka M, Kurose A, Fumoto T, Saito K, Sonoda Y, Ogasawara K, Fujii Y, Shimizu H, Ohkuma H, Kitanaka C, Kayama T, Tominaga T.
    • Journal Title

      Brain Tumor Pathol

      Volume: 印刷中 Issue: 3 Pages: 139-150

    • DOI

      10.1007/s10014-022-00427-4

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Real-World status and risk factors for a poor prognosis in elderly patients with primary central nervous system malignant lymphomas: a multicenter, retrospective cohort study of the Tohoku Brain Tumor Study Group2022

    • Author(s)
      Asano K, Yamashita Y, Ono T, Natsumeda M, Beppu T, Matsuda K, Ichikawa M, Kanamori M, Matsuzaka M, Kurose A, Saito K, Sonoda Y, Ogasawara K, Fujii Y, Shimizu H, Ohkuma H, Kitanaka C, Kayama T, Tominaga T.
    • Journal Title

      Int J Clin Oncol

      Volume: 27 Issue: 1 Pages: 77-94

    • DOI

      10.1007/s10147-021-02042-3

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Safety and efficacy of depatuxizumab mafodotin in Japanese patients with malignant glioma: A nonrandomized, phase 1/2 trial.2021

    • Author(s)
      Narita Y, Muragaki Y, Kagawa N, Asai K, Nagane M, Matsuda M, Ueki K, Kuroda J, Date I, Kobayashi H, Kumabe T, Beppu T, Kanamori M, Kasai S, Nishimura Y, Xiong H, Ocampo C, Yamada M, Mishima K.
    • Journal Title

      Cancer Sci.

      Volume: 12 Issue: 12 Pages: 5020-5033

    • DOI

      10.1111/cas.15153

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Primary Cranial Vault Lymphoma Extending between Subcutaneous Tissue and Brain Parenchyma without Skull Destruction after Mild Head Trauma: A Case Report and Literature Review2021

    • Author(s)
      Setta Kengo、Beppu Takaaki、Sato Yuichi、Saura Hiroaki、Nomura Junichi、Sugai Tamotsu、Ogasawara Kuniaki
    • Journal Title

      Case Reports in Oncology

      Volume: 14 Issue: 2 Pages: 1118-1123

    • DOI

      10.1159/000516272

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Primary plasmacytoma in the cerebellum: A case report and literature review.2019

    • Author(s)
      Yanagihara W, Beppu T, Ogasawara Y, Ito S, Sato Y, Sugai T, Ogasawara K.
    • Journal Title

      World Neurosurg.

      Volume: 134 Pages: 10-13

    • DOI

      10.1016/j.wneu.2019.10.036

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Synergistic effect from combination of tumor-treating fields therapy (TTF) and temozolomide in a patient with secondary glioblastoma.2022

    • Author(s)
      Beppu T
    • Organizer
      Clinical Excellence in GBM meeting
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 膠芽腫に対する術前アバスチン投与の有用性2022

    • Author(s)
      別府髙明、佐藤雄一、野村順一、藤原俊朗、小笠原邦昭
    • Organizer
      第81回日本脳神経外科学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 膠芽腫に対する術前ベバシズマブ投与の臨床的意義2022

    • Author(s)
      別府髙明、佐藤雄一、野村順一、藤原俊朗、小笠原邦昭
    • Organizer
      第40回日本脳腫瘍学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 膠芽腫における低酸素細胞トレーサー18F-FRP170集積部位の腫瘍内環境2021

    • Author(s)
      別府髙明、佐藤雄一、佐々木敏秋、寺崎一典、藤原俊朗、小笠原邦昭
    • Organizer
      第44回日本脳神経CI学会
    • Related Report
      2021 Research-status Report
  • [Presentation] メチオニンPETはlower grade gliomaのテモゾロマイド維持療法中止時の予後予測に有用か2021

    • Author(s)
      別府髙明、佐藤雄一、佐々木敏秋、寺崎一典、岩谷岳、小笠原邦昭
    • Organizer
      第80回日本脳神経外科学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] メチオニンPETによるIDH変異型低悪性神経膠腫の維持療法終了時における予後予測2021

    • Author(s)
      別府髙明、佐藤雄一、佐々木敏秋、寺崎一典、岩谷岳、小笠原邦昭
    • Organizer
      第39回日本脳腫瘍学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 膠芽腫における低酸素細胞トレーサー18F-FRP170集積部位の腫瘍内環境2021

    • Author(s)
      別府髙明、佐藤雄一、佐々木敏秋、寺崎一典、藤原俊朗、小笠原邦昭
    • Organizer
      第44回日本脳神経CI学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 1C-methionine PETはテモゾロマイド維持療法終了の判断とその後の予後予測に有用か2020

    • Author(s)
      別府髙明、佐藤雄一、小笠原邦昭
    • Organizer
      第79回日本脳神経外科学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 11C-methionine PETはテモゾロマイド維持療法終了の決定2020

    • Author(s)
      別府髙明、佐藤雄一、小笠原邦昭
    • Organizer
      第38回日本脳腫瘍学会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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