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Radiobiological effects of novel brachytherapy using alfa-radiation sources for oral cancer

Research Project

Project/Area Number 20H03886
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

MIURA MASAHIKO  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (10272600)

Co-Investigator(Kenkyū-buntansha) 宇尾 基弘  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (20242042)
戒田 篤志  東京医科歯科大学, 東京医科歯科大学病院, 助教 (40632097)
小野里 祐佑  東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (10844300)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2022: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2021: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2020: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords口腔がん / 小線源治療 / α線源
Outline of Research at the Start

我々の施設では、頭頸部がんの再発腫瘍に対し、α線源を用いた小線源治療法による治験を開始した。線源は、Ra-224でそこからRn-220が気化し、組織内に拡散することで腫瘍がα線照射される。しかしながら、線源近傍でどのような放射線生物学的現象が起こっているのか、基礎生物学的な解析はほとんど行われていない。本研究では、これまでの研究を踏まえ、DNA損傷応答(DDR)がその領域でどのように起こっているかを娘核種の分布と対応させながら可視化し、さらに、どのような生物学的因子がその拡散やDDRに影響を与え、どうすればより効率の高い効果が得られるのかを検討し、実臨床への還元を目指す。

Outline of Final Research Achievements

Diffusing alpha-emitters radiation therapy (Alpha-DaRT) is a unique method, in which interstitial sources carrying Ra-224 release a chain of short-lived daughter atoms from their surface. Although DNA damage response (DDR) is crucial to inducing cell death after irradiation, how the DDR occurs during Alpha-DaRT treatment has not yet been explored. In this study, we temporo-spatially characterized DDR such as kinetics of DNA double-strand breaks (DSBs) and cell cycle, in two-dimensional (2D) culture conditions qualitatively mimicking Alpha-DaRT treatments, by employing HeLa cells expressing the Fucci cell cycle-visualizing system. A medium containing daughter nuclides prepared from Ra-224 sources allowed us to estimate the radiation dose after 24 h of exposure, and determine surviving fractions. The present experimental model revealed for the first time temporo-spatial information of DDR occurring around the source in its early stages and we attempted to apply the data to clinics.

Academic Significance and Societal Importance of the Research Achievements

Diffusing alpha-emitters radiation therapy (Alpha-DaRT)は、現在PMDAによる承認間近な状況となっている。しかしながら、基礎的な検討は十分になされていなかった。そこで、本研究では、細胞周期、DNA損傷、α粒子を可視化する方法を導入して早期のDNA損傷応答を可視化したところ、FucciによるG2アレスト細胞が、他の指標よりより高感度に検出されることがわかり、今後の前臨床試験を実施する上で、治療による有効性を確認するための有用な指標となりうることが示唆された。

Report

(4 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (45 results)

All 2024 2023 2022 2021 2020 Other

All Int'l Joint Research (1 results) Journal Article (12 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 12 results,  Open Access: 11 results) Presentation (29 results) (of which Int'l Joint Research: 1 results,  Invited: 11 results) Book (3 results)

  • [Int'l Joint Research] Ben-Gurion University of the Negev/Alpha Tau Medical 社(イスラエル)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] DNA damage response in a 2D-culture model by diffusing alpha-emitters radiation therapy (Alpha-DaRT)2024

    • Author(s)
      Nojima Hitomi、Kaida Atsushi、Matsuya Yusuke、Uo Motohiro、Yoshimura Ryo-ichi、Arazi Lior、Miura Masahiko
    • Journal Title

      Scientific Reports

      Volume: 14 Issue: 1 Pages: 11468-11468

    • DOI

      10.1038/s41598-024-62071-6

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Potential of preoperative fluorodeoxyglucose-positron emission tomography/computed tomography to diagnose contralateral lymph node metastases in patients with oral cancer2023

    • Author(s)
      Wamasing Natnicha、Nakamura Shin、Watanabe Hiroshi、Kuribayashi Ami、Miura Masahiko
    • Journal Title

      Nuclear Medicine Communications

      Volume: 44 Issue: 12 Pages: 1168-1175

    • DOI

      10.1097/mnm.0000000000001765

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Invasion of the bucco-mandibular space by oral squamous cell carcinoma: histopathological analysis of invasion pattern2023

    • Author(s)
      Kugimoto Takuma、Nishii Naoto、Oikawa Yu、Kuroshima Takeshi、Hirai Hideaki、Tomioka Hirofumi、Michi Yasuyuki、Kayamori Kou、Sakamoto Junichiro、Iwanaga Joe、Tubbs R. Shane、Ikeda Tohru、Miura Masahiko、Harada Hiroyuki
    • Journal Title

      Frontiers in Oncology

      Volume: 13 Pages: 1168376-1168376

    • DOI

      10.3389/fonc.2023.1168376

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of Ablative Dose Irradiation on Redistribution and Radioresponse in a Mouse Xenograft Model2022

    • Author(s)
      Nojima Hitomi、Kaida Atsushi、Harada Hiroyuki、Akiyama Masako、Miura Masahiko
    • Journal Title

      Radiation Research

      Volume: 198 Issue: 6 Pages: 632-638

    • DOI

      10.1667/rade-22-00096.1

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Retrograde Migration of an Au-198 Grain to the Submandibular Gland Post Brachytherapy Treatment of Floor of Mouth Cancer2022

    • Author(s)
      Nojima Hitomi、Kaida Atsushi、Kuroshima Takeshi、Yoshimura Ryo-ichi、Miura Masahiko
    • Journal Title

      Cureus

      Volume: 14

    • DOI

      10.7759/cureus.31904

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Determination of Clonogenic Radiosensitivity of HeLa Cells in Early and Late G<sub>1</sub>Phases2022

    • Author(s)
      TOHYAMA KOHKI、KAIDA ATSUSHI、MIURA MASAHIKO
    • Journal Title

      Anticancer Research

      Volume: 42 Issue: 11 Pages: 5407-5413

    • DOI

      10.21873/anticanres.16045

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Roles of IGFBP-3 in cell migration and growth in an endophytic tongue squamous cell carcinoma cell line2022

    • Author(s)
      Ng Esther Feng Ying、Kaida Atsushi、Nojima Hitomi、Miura Masahiko
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 11503-11503

    • DOI

      10.1038/s41598-022-15737-y

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 再発・転移頭頸部癌に対する網羅的がんゲノム解析と臨床的有用性2021

    • Author(s)
      遠山皓基, 加納嘉人, 野地理夏, 青柳康子, 松寺翔太郎, 大野十央, 有泉陽介, 道泰介, 富岡寛文, 島本裕彰, 吉村亮一, 朝蔭孝宏, 原田浩之, 三宅智, 三浦雅彦, 池田貞勝
    • Journal Title

      頭頚部癌

      Volume: 47 Pages: 359-366

    • NAID

      130008145015

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy and Safety of Induction Chemotherapy and/or External Beam Radiotherapy Followed by Brachytherapy in Patients With Tongue Cancer2021

    • Author(s)
      YOSHIMURA RYO-ICHI、TODA KAZUMA、WATANABE HIROSHI、KAIDA ATSUSHI、HARADA HIROYUKI、ASAKAGE TAKAHIRO、MIURA MASAHIKO
    • Journal Title

      Anticancer Research

      Volume: 41 Issue: 12 Pages: 6259-6266

    • DOI

      10.21873/anticanres.15446

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic impact of lingual lymph node metastasis in patients with squamous cell carcinoma of the tongue: a retrospective study2021

    • Author(s)
      Kuroshima Takeshi、Onozato Yusuke、Oikawa Yu、Ohsako Toshimitsu、Kugimoto Takuma、Hirai Hideaki、Tomioka Hirofumi、Michi Yasuyuki、Miura Masahiko、Yoshimura Ryoichi、Harada Hiroyuki
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 20535-20535

    • DOI

      10.1038/s41598-021-99925-2

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prolonged cetuximab treatment promotes p27Kip1-mediated G1 arrest and autophagy in head and neck squamous cell carcinoma2021

    • Author(s)
      Okuyama Kohei、Suzuki Keiji、Naruse Tomofumi、Tsuchihashi Hiroki、Yanamoto Souichi、Kaida Atsushi、Miura Masahiko、Umeda Masahiro、Yamashita Shunichi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 5259-5259

    • DOI

      10.1038/s41598-021-84877-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fluctuation in radioresponse of HeLa cells during the cell cycle evaluated based on micronucleus frequency2020

    • Author(s)
      Shimono Hiroaki、Kaida Atsushi、Homma Hisao、Nojima Hitomi、Onozato Yusuke、Harada Hiroyuki、Miura Masahiko
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 20973-20973

    • DOI

      10.1038/s41598-020-77969-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 高齢口腔がん診療臨床的指針 高齢口腔癌患者に対する放射線治療2024

    • Author(s)
      三浦雅彦、伊川裕明、武者篤、戒田篤志、森川貴迪
    • Organizer
      第42会日本口腔腫瘍学会学術大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 放射線感受性の細胞周期依存性を再考する2023

    • Author(s)
      三浦雅彦
    • Organizer
      第23回菅原・大西記念癌治療増感シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 超高齢者社会の口腔癌治療の現状2023

    • Author(s)
      三浦雅彦、伊川裕明、武者篤、戒田篤志、森川貴迪
    • Organizer
      第41回日本口腔腫瘍学会学術大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 新規小線源治療Diffusing Alpha-Emitters Radiation Therapy (DaRT)によるin vitroにおけるDNA損傷応答2023

    • Author(s)
      野島瞳、戒田篤志、宇尾基弘、三浦雅彦
    • Organizer
      第88回口腔病学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Au-198 grainを用いたモールド療法の早期口腔がんへの有効性2023

    • Author(s)
      野島瞳、戒田篤志、原田美穂子、三浦雅彦
    • Organizer
      第68回日本口腔外科学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 細胞周期可視化マウス腫瘍モデルを用いた1回大線量分割照射における再分布の意義2023

    • Author(s)
      野島瞳、戒田篤志、三浦雅彦
    • Organizer
      第60回日本放射線腫瘍学会生物部会学術大会・第51回放射線による制癌シンポジウム
    • Related Report
      2022 Annual Research Report
  • [Presentation] 口腔癌に対する小線源治療後にAu-198grainの顎下腺への逆行性移動がみられた一例2023

    • Author(s)
      野島瞳、戒田篤志、三浦雅彦
    • Organizer
      日本歯科放射線学会第63回学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] α線源を用いた新規小線源治療DaRTにおける生物学的効果の検討2023

    • Author(s)
      野島瞳、戒田篤志、三浦雅彦
    • Organizer
      第41回日本口腔腫瘍学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ”Hallmarks of cancer”から読み解く放射線生物学2022

    • Author(s)
      三浦雅彦
    • Organizer
      日本放射線腫瘍学会第35回学術大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 頭頸部の密封小線源治療ー頭頸部小線源治療事情ー2022

    • Author(s)
      吉村亮一、桑原宏文、長野拓也、松原大五郎、三木谷智範、野島瞳、戒田篤志、三浦雅彦
    • Organizer
      第59回日本医学放射線学会秋季臨床大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Introduction to radiotherapy for oral cancer,2022

    • Author(s)
      Masahiko MIURA
    • Organizer
      The 13th Asian Congress of Oral and Maxillo-Facial Radiology, The 62nd Japanese Society for Oral and Maxillo-Facial Radiology
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 6R(+1)から見た前立腺癌に対するSBRTとHDRの効果2022

    • Author(s)
      三浦雅彦
    • Organizer
      日本放射線腫瘍学会小線源治療部会第24回学術大会,
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Diffusing Alpha-emitters Radiation Therapy(DaRT)による線源周囲でのDNA損傷応答2022

    • Author(s)
      野島瞳、戒田篤志、三浦雅彦
    • Organizer
      日本放射線腫瘍学会第59回生物部会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 細胞周期チェックポイント阻害剤による口腔がん細胞の細胞周期動態変化と細胞死様式2022

    • Author(s)
      野島瞳、戒田篤志、原田浩之、三浦雅彦
    • Organizer
      第76回日本口腔科学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 10年後の量子医科学における生物の役割2021

    • Author(s)
      三浦雅彦
    • Organizer
      第1回日本量子医科学会学術大会領域合同シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 高線量放射線照射後の腫瘍内酸素環境の変化に基づく寡分割照射法の再考2021

    • Author(s)
      三浦雅彦
    • Organizer
      日本放射線腫瘍学会第34回学術大会シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 細胞周期動態の可視化から見た放射線応答2021

    • Author(s)
      三浦雅彦
    • Organizer
      第1回日本放射線影響学会・若手部会・放射線影響研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 放射線照射後のG2アレスト動態が細胞運命に及ぼす影響2021

    • Author(s)
      戒田篤志、三浦雅彦
    • Organizer
      日本放射線腫瘍学会第34回学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 放射線照射後に生じる腫瘍細胞の再分布から考える定位放射線治療の生物学的有効性2021

    • Author(s)
      野島瞳、戒田篤志、三浦雅彦
    • Organizer
      日本放射線腫瘍学会第58回生物部会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 口腔がんの定位放射線治療に置ける再分布の意義2021

    • Author(s)
      野島瞳、戒田篤志、原田浩之、三浦雅彦
    • Organizer
      日本歯科放射線学会第61回学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] がんゲノム解析によりニボルマブ耐性機構が示唆された再発頬粘膜癌の一例2021

    • Author(s)
      野地理夏、加納嘉人、平井秀明、山下大和、工藤亮、富岡寛文、島本裕彰、道泰之、大西威一郎、三浦雅彦、吉村亮一、三宅智、池田貞勝、原田浩之
    • Organizer
      第45回日本頭頸部癌学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 低酸素細胞増感剤開発の経験と実用化の現実2021

    • Author(s)
      三浦雅彦
    • Organizer
      日本放射線腫瘍学会第11回放射線生物学セミナー
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 頭頸部癌に対するがんゲノム解析と臨床的有用性2021

    • Author(s)
      加納嘉人、三浦雅彦 et al.
    • Organizer
      第18回日本臨床腫瘍学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 口腔扁平上皮癌細胞を用いた定位放射線治療の効果とG2アレストの関連性の検討2021

    • Author(s)
      野島瞳、戒田篤志、三浦雅彦
    • Organizer
      第39回日本口腔腫瘍学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] セツキシマブの長期処理がもたらす舌癌細胞遊走能の抑制はp27Kip1依存性G1アレストとオートファジーを誘導する2021

    • Author(s)
      奥山紘平、戒田篤志、三浦雅彦 et al.
    • Organizer
      第39回日本口腔腫瘍学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 舌扁平上皮癌における舌リンパ節転移の臨床病理学的検討2021

    • Author(s)
      黒嶋雄志、小野里祐佑、三浦雅彦 et al.
    • Organizer
      第39回日本口腔腫瘍学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 口腔癌に対するがんゲノム解析と臨床的有用性2021

    • Author(s)
      野地理夏、加納嘉人、三浦雅彦 et al.
    • Organizer
      第39回日本口腔腫瘍学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 再発・転移頭頚部癌に対するがんゲノムリアルワールド解析と有用性2020

    • Author(s)
      遠山皓基、加納嘉人、三浦雅彦 et al.
    • Organizer
      第44回頭頸部癌学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 舌扁平上皮癌StageⅠ・Ⅱ症例における小線源治療の臨床的検討2020

    • Author(s)
      平井秀明、及川悠、三浦雅彦 et al.
    • Organizer
      第44回頭頸部癌学会
    • Related Report
      2020 Annual Research Report
  • [Book] 口腔癌, 口腔癌の放射線療法、薬物療法、免疫療法, 1章 放射線療法, 1 基礎知識2023

    • Author(s)
      三浦雅彦 他
    • Total Pages
      724
    • Publisher
      医歯薬出
    • Related Report
      2022 Annual Research Report
  • [Book] 必修 視覚で学ぶ歯科放射線学2022

    • Author(s)
      三浦雅彦 他
    • Total Pages
      178
    • Publisher
      砂書房
    • Related Report
      2022 Annual Research Report
  • [Book] Methods Mol Biol2021

    • Author(s)
      Atsushi Kaida, Masahiko Miura
    • Total Pages
      352
    • Publisher
      Spring Nature
    • Related Report
      2021 Annual Research Report

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

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