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Development of new boron-drugs and models for BNCT targeting malignant cells.

Research Project

Project/Area Number 21K04790
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 27040:Biofunction and bioprocess engineering-related
Research InstitutionOkayama University

Principal Investigator

Kasai Tomonari  岡山大学, 中性子医療研究センター, 准教授 (30530191)

Co-Investigator(Kenkyū-buntansha) 岩崎 良章  岡山大学, 保健管理センター, 教授 (00314667)
杉山 友康  東京工科大学, 応用生物学部, 教授 (30367198)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsホウ素中性子捕捉療法 / ホウ素薬剤 / 悪性がん / がん幹細胞 / 動物モデル / 人工多能性幹細胞 / BNCT / iPS細胞
Outline of Research at the Start

ホウ素中性子捕捉療法(BNCT: Boron Neutron Capture Therapy)の治療効果はホウ素薬剤のがん細胞への特異性とがん細胞内に蓄積したホウ素10B濃度に大きく依存する。腫瘍組織の中には多様ながん細胞が存在するため、取り込み機序が異なる複数の薬剤を併用する必要がある。不均一ながん幹細胞を標的とするホウ素薬剤開発と新規ホウ素薬剤の取り込み量を予測するシステムの構築を目指す。

Outline of Final Research Achievements

The new boron-drug uptake and gene expression level were confirmed by using the liver cancer stem cell model derived from mouse iPS cells and human cancer cell lines. We developed a model for boron uptake from gene expression levels and measured the boron uptake of cancer cell lines. As a result, 70% of cancer cell lines were matched with the prediction. It was found that the concentration of a new boron agent taken into the cell was greatly influenced by not only cell surface markers, but the factors thought to be involved in intracellular retention, The novel boron drug has a high possibility of cancer cell elimination by boron neutron capture reaction, since it was observed that the drugs accumulate in the nucleus and in intracellular organelles involved in metabolism.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果から、1回の照射だけでがんを全て消滅する技術開発が期待でき、それによって再発や転移のリスクを回避することが期待できる。すなわち、新規ホウ素薬剤を開発しBPAと併用することによって、多様な性質を有するがん細胞全てにホウ素(10B)を高濃度で行き渡らせることを可能とする。また、正常細胞を始点として、CSCsおよびがん細胞までの様々な細胞について、新規ホウ素薬剤の取り込みを予測する技術を構築し、殺傷効果を検証した。適応疾患の拡大だけでなく、がん早期診断法の開発やペプチドを用いた新規薬剤開発にも繋がる。BNCTによる悪性がん根治を目指して更に発展した研究が期待できる。

Report

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

    (28 results)

All 2024 2023 2022 2021

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (19 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] The current status and novel advances of boron neutron capture therapy clinical trials2024

    • Author(s)
      Zhou Tianyun, Kazuyo Igawa, Tomonari Kasai, Takuya Sadahira, Wei Wang, Tomofumi Watanabe, Kensuke Bekku, Satoshi Katayama, Takehiro Iwata, Tadashi Hanafusa.
    • Journal Title

      American Journal of Cancer Research

      Volume: 14 Issue: 2 Pages: 429-447

    • DOI

      10.62347/hbbe6868

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Particle and Heavy Ion Transport Code System-Based Microdosimetry for the Development of Boron Agents for Boron Neutron Capture Therapy2023

    • Author(s)
      Takafumi Shigehira, Tadashi Hanafusa, Kazuyo Igawa, Tomonari Kasai, Shuichi Furuya, Hisakazu Nishimori, Yoshinobu Maeda, Hiroyuki Michiue, Atsushi Fujimura
    • Journal Title

      Advanced Theory and Simulations

      Volume: - Issue: 7 Pages: 2332-2342

    • DOI

      10.1002/adts.202300163

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A new strategy for screening novel functional genes involved in reduction of lipid droplet accumulation2023

    • Author(s)
      Maruyama Ryuto、Kudo Yasuhiro、Sugiyama Tomoyasu
    • Journal Title

      BioFactors

      Volume: 81 Issue: 3 Pages: 459-468

    • DOI

      10.1002/biof.2019

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deep Learning of Phase-Contrast Images of Cancer Stem Cells Using a Selected Dataset of High Accuracy Value Using Conditional Generative Adversarial Networks2023

    • Author(s)
      Zhang Zaijun、Ishihata Hiroaki、Maruyama Ryuto、Kasai Tomonari、Kameda Hiroyuki、Sugiyama Tomoyasu
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 6 Pages: 5323-5323

    • DOI

      10.3390/ijms24065323

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of the anti-inflammatory drug celecoxib on cell death signaling in human colon cancer2023

    • Author(s)
      Maruyama Ryuto、Kiyohara Yuki、Kudo Yasuhiro、Sugiyama Tomoyasu
    • Journal Title

      Naunyn-Schmiedeberg's Archives of Pharmacology

      Volume: - Issue: 6 Pages: 1171-1185

    • DOI

      10.1007/s00210-023-02399-4

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Case of Autoimmune Gastritis and Hepatitis with Enlarging Gastric Polyps after Reducing the Dose of Prednisolone2023

    • Author(s)
      Katsumata Ryo、Kamada Tomoari、Murao Takahisa、Sunago Aya、Suehiro Mitsuhiko、Monobe Yasumasa、Iwasaki Yoshiaki、Kawamoto Hirofumi、Nagai Hiroshi、Haruma Ken
    • Journal Title

      Case Reports in Gastroenterology

      Volume: 17 Issue: 1 Pages: 117-123

    • DOI

      10.1159/000529151

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Temporal and Locational Values of Images Affecting the Deep Learning of Cancer Stem Cell Morphology2022

    • Author(s)
      Hanai Yumi, Ishihata Hiroaki, Zhang Zaijun, Maruyama Ryuto, Kasai Tomonari, Kameda Hiroyuki, Sugiyama Tomoyasu
    • Journal Title

      Biomedicines

      Volume: 10 Issue: 5 Pages: 941-941

    • DOI

      10.3390/biomedicines10050941

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Levocarnitine may improve the survival of patients with liver cirrhosis who undergo cell-free and concentrated ascites reinfusion therapy for refractory ascites2021

    • Author(s)
      Kawaji Hiromichi、Moriya Akio、Nagahara Teruya、Iwasaki Yoshiaki、Ando Masaharu
    • Journal Title

      Kanzo

      Volume: 62 Issue: 10 Pages: 663-666

    • DOI

      10.2957/kanzo.62.663

    • NAID

      130008101720

    • ISSN
      0451-4203, 1881-3593
    • Year and Date
      2021-10-01
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Living with Family Is Directly Associated with Regular Dental Checkup and Indirectly Associated with Gingival Status among Japanese University Students: A 3-Year Cohort Study2021

    • Author(s)
      Nakahara Momoko、Ekuni Daisuke、Kataoka Kota、Yokoi Aya、Uchida-Fukuhara Yoko、Fukuhara Daiki、Kobayashi Terumasa、Toyama Naoki、Saho Hikari、Islam Md Monirul、Iwasaki Yoshiaki、Morita Manabu
    • Journal Title

      International Journal of Environmental Research and Public Health

      Volume: 18 Issue: 1 Pages: 324-324

    • DOI

      10.3390/ijerph18010324

    • NAID

      120007004819

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 人工知能が識別したがん幹細胞を深層学習した人工知能の開発2023

    • Author(s)
      杉山友康、張再軍、石畑宏明、丸山竜人、笠井智成、亀田弘之
    • Organizer
      第75回日本生物工学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 水晶振動子マイクロバランス法と画像解析による細胞老化のモニタリング2023

    • Author(s)
      山口響、村松宏、杉山友康
    • Organizer
      第75回日本生物工学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ヒト結腸がん細胞株HCT116のROSレベルの増加を誘導するshRNAのRNAiスクリーニング2022

    • Author(s)
      工藤康博、丸山竜人、杉山友康
    • Organizer
      2022年度 日本生化学会関東支部例会
    • Related Report
      2022 Research-status Report
  • [Presentation] CoQ合成酵素遺伝子PDSS2のノックダウンによる細胞の膜酸化の検討2022

    • Author(s)
      若松音子、丸山竜人、藤沢章雄、杉山友康
    • Organizer
      2022年度 日本生化学会関東支部例会
    • Related Report
      2022 Research-status Report
  • [Presentation] がん細胞分裂を抑制する人工核酸のRNAiスクリーニング2022

    • Author(s)
      岩永遼,丸山竜人,工藤康博,樋口浄,杉山友康
    • Organizer
      日本核酸医薬学会第7回年会
    • Related Report
      2022 Research-status Report
  • [Presentation] 深層学習法を応用したがん幹細胞形態の認識技術の開発2022

    • Author(s)
      杉山友康、花井優未、石畑宏明、張再軍、丸山竜人、笠井智成、亀田弘之
    • Organizer
      第45回日本分子生物学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 若年成人の非アルコール性脂肪性肝疾患におけるFIB-4 indexの検討2022

    • Author(s)
      岩崎 良章, 中山 光, 池田 房雄, 高木 章乃夫, 岡田 裕之
    • Organizer
      第26回日本肝臓学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 腹水濾過濃縮再静注法におけるカルニチン喪失に関する検討2022

    • Author(s)
      守屋 昭男, 川地 紘通, 永原 照也, 岩崎 良章, 安東 正晴
    • Organizer
      第26回日本肝臓学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 若年成人の非アルコール性脂肪性肝疾患におけるPTGER4遺伝子多型の検討2022

    • Author(s)
      岩崎 良章, 中山 光, 池田 房雄, 和田 望, 高木 章乃夫, 岡田 裕之
    • Organizer
      第26回日本肝臓学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Relationship between fatty liver and high-sensitivity C-reactive protein2021

    • Author(s)
      Hideaki Taniguchi, Yoshiaki Iwasaki, Masahito Aimi, Hiroshi Matsushita
    • Organizer
      United European Gastroenterology UEG Week Virtual 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 若年成人のトランスアミナーゼ異常における脂肪肝関連遺伝子多型の検討2021

    • Author(s)
      岩崎良章、中山 光、池田房雄、和田 望、安中哲也、高木章乃夫、岡田裕之
    • Organizer
      第57回日本肝臓学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 人間ドック受診者で認められたMetabolic associated fatty liver disease (MAFLD)とnon-alcoholic fatty liver disease (NAFLD)の比較2021

    • Author(s)
      守屋昭男、岩崎良章、永原 照也、安東正晴
    • Organizer
      第57回日本肝臓学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] レボカルニチン投与は難治性腹水に対し腹水濾過濃縮再静注を実施されている肝硬変患者の予後改善に寄与する可能性がある2021

    • Author(s)
      守屋昭男、川地紘通、永原 照也、岩崎良章、安東正晴
    • Organizer
      第57回日本肝臓学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 非アルコール性脂肪性肝疾患におけるPTGER4遺伝子多型と肝線維化の検討2021

    • Author(s)
      岩崎良章、池田房雄、中山 光、高木章乃夫、岡田裕之
    • Organizer
      第25回日本肝臓学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 若年成人の非アルコール性脂肪性肝疾患における遺伝子多型と血中脂質の検討2021

    • Author(s)
      岩崎良章、中山 光、池田房雄、和田 望、安中哲也、高木章乃夫、岡田裕之
    • Organizer
      第25回日本肝臓学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 人間ドックにおけるMetabolic associated fatty liver disease (MAFLD)の経時的特徴2021

    • Author(s)
      守屋昭男、岩崎良章、永原 照也、安東正晴
    • Organizer
      第25回日本肝臓学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 脂肪肝と高感度CRPとの関連について2021

    • Author(s)
      谷口英明、岩崎良章、相見正史、松下浩志
    • Organizer
      第63回消化器病学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Segmentation of cancer stem cell using CGAN2021

    • Author(s)
      Tomoyasu Sugiyama
    • Organizer
      The 15th IEEE International Conference on Nano/Molecular Medicine & Engineering (IEEE-NANOMED 2021)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] がん幹細胞を識別する人工知能のための基礎研究2021

    • Author(s)
      杉山友康
    • Organizer
      ファーマTI & デジタルヘルスケア2021
    • Related Report
      2021 Research-status Report
    • Invited

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

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