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Analysis of neutral amino acid metabolism after X-irradiation and Radio-sensitization by targeting amino acid metabolism

Research Project

Project/Area Number 21K14971
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 42020:Veterinary medical science-related
Research InstitutionYamagata University

Principal Investigator

BO TOMOKI  山形大学, 医学部, 助教 (90878141)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsがん / 分岐鎖アミノ酸 / 代謝 / 放射線療法 / 中性アミノ酸 / 放射線 / エネルギー代謝
Outline of Research at the Start

申請者は中性アミノ酸輸送体LAT1阻害ががん放射線増感効果をもたらす結果を得たことから、放射線照射が中性アミノ酸代謝を亢進し、これが放射線照射後の細胞生存に働くのではないかと仮説を立てた。本研究では仮説立証のために、中性アミノ酸の動態をエネルギー代謝の面から解析し、中性アミノ酸代謝の放射線応答についても調べる。これらの検討から、がん細胞の中性アミノ酸代謝を標的とした新たながん治療法の開発を目指す。

Outline of Final Research Achievements

In this study, we analyze cancer neutral amino acids metabolism in terms of energy metabolism after X-irradiation. We investigated the radiation response of neutral amino acid metabolism to develop a new cancer therapy targeting neutral amino acid metabolism in cancer cells. (1) We attempted radiosensitization targeting the branched-chain amino acid metabolic process among neutral amino acids. (2) We evaluated the energy response to X-irradiation when branched-chain amino acid metabolism was inhibited. (3) We also provided the mechanism of radiosensitization by inhibiting the branched-chain amino acid metabolic process. Based on the above studies, we succeeded in obtaining basic data for the development of novel radiotherapy by realizing radiosensitization targeting branched-chain amino acid metabolism.

Academic Significance and Societal Importance of the Research Achievements

本研究により中性アミノ酸代謝のうち分岐鎖アミノ酸を標的とした放射線増感効果が実証することができたことから、新規がん放射線療法の開発につながる基礎データを得られた。また、がん細胞におけるアミノ酸代謝過程の理解が進めることができ、新規のがん治療標的を確立する上で意義ある研究結果となった。本知見は、放射線照射を受けたがん細胞の生存戦略におけるアミノ酸代謝の担う役割の理解に繋がり、放射線生物学の知見をより一層深化させただけでなく、アミノ酸代謝を標的とした新規がん放射線療法の開発につながる知見となった。

Report

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

    (10 results)

All 2024 2023 2022 2021

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Ascorbic Acid Protects Bone Marrow from Oxidative Stress and Transient Elevation of Corticosterone Caused by X-ray Exposure in Akr1a-Knockout Mice2024

    • Author(s)
      Bo Tomoki、Nohara Hidekazu、Yamada Ken-ichi、Miyata Satoshi、Fujii Junichi
    • Journal Title

      Antioxidants

      Volume: 13 Issue: 2 Pages: 152-152

    • DOI

      10.3390/antiox13020152

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Heme Biosynthesis is Crucial for Cell Survival and Mitochondrial OXPHOS after X Irradiation2023

    • Author(s)
      Bo Tomoki、Van Wijk Koen、Nakajima Osamu
    • Journal Title

      Radiation Research

      Volume: 201 Issue: 1 Pages: 48-54

    • DOI

      10.1667/rade-23-00035.1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ascorbate Is a Primary Antioxidant in Mammals2022

    • Author(s)
      Fujii Junichi、Osaki Tsukasa、Bo Tomoki
    • Journal Title

      Molecules

      Volume: 27 Issue: 19 Pages: 6187-6187

    • DOI

      10.3390/molecules27196187

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] LAT1 inhibitor JPH203 sensitizes cancer cells to radiation by enhancing radiation-induced cellular senescence2021

    • Author(s)
      Bo Tomoki、Kobayashi Sho、Inanami Osamu、Fujii Junichi、Nakajima Osamu、Ito Tsunekata、Yasui Hironobu
    • Journal Title

      Translational Oncology

      Volume: 14 Issue: 11 Pages: 101212-101212

    • DOI

      10.1016/j.tranon.2021.101212

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Heme biosynthesis is upregulated to enhance oxidative phosphorylation for cell survival after X-irradiation2023

    • Author(s)
      Tomoki BO
    • Organizer
      17th International Congress of Radiation Research
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibition of BCAT1 and BCKDHα enhances cancer radiosensitivity.2023

    • Author(s)
      Tomoki BO
    • Organizer
      日本放射線影響学会第66回大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] The effect of inhibition of heme synthesis on cellular survival and mitochondrial function after X-irradiation2022

    • Author(s)
      Tomoki Bo, Koen Van Wijk, Tsunekata Ito, Osamu Nakajima
    • Organizer
      日本放射線影響学会第65回大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Succinyl acetoneによるヘム生合成阻害はX線照射後のミトコンドリア機能亢進を抑制し放射線誘発細胞死を増強する2022

    • Author(s)
      房 知輝,Koen Van Wijk,伊藤 恒賢,中島 修
    • Organizer
      第30回山形分子生物学セミナー
    • Related Report
      2022 Research-status Report
  • [Presentation] 中性アミノ酸輸送体 LAT1阻害剤 JPH203によるがん放射線増感効果の評価とメカニズムの解明2021

    • Author(s)
      房知輝、小林翔、伊藤恒賢、中島修、藤井順逸
    • Organizer
      第74回日本酸化ストレス学会/第21回日本NO学会合同学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] LAT1 inhibitor JPH203 enhances radiation-induced cellular senescence by downregulation of mTOR activity2021

    • Author(s)
      Tomoki Bo, Sho Kobayashi, Osamu Inanami, Junichi Fujii, Osamu Nakajima, Tsunekata Ito, Hironobu Yasui
    • Organizer
      日本放射線影響学会第63回大会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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