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Research and development about helium and proton hybrid system with proton CT and Immuno-radiotherapy

Research Project

Project/Area Number 19H03591
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 InstitutionHokkaido University

Principal Investigator

Shirato Hiroki  北海道大学, 医学研究院, 教授 (20187537)

Co-Investigator(Kenkyū-buntansha) 宮本 直樹  北海道大学, 工学研究院, 准教授 (00552879)
高尾 聖心  北海道大学, 工学研究院, 准教授 (10614216)
茶本 健司  京都大学, 医学研究科, 特定教授 (50447041)
橋本 孝之  北海道大学, 医学研究院, 教授 (60400678)
Nam JinMin  京都大学, 生命科学研究科, 准教授 (60414132)
西岡 健太郎  北海道大学, 医学研究院, 助教 (80463743)
久我 悠馬  医療法人徳洲会札幌東徳洲会病院医学研究所, IBD・免疫研究部, 研究員 (80971522)
小野寺 康仁  北海道大学, 医学研究院, 准教授 (90435561)
松浦 妙子  北海道大学, 工学研究院, 教授 (90590266)
梅垣 菊男  北海道大学, 工学研究院, 特任教授 (40643193)
平田 雄一  北海道大学, アイソトープ総合センター, 准教授 (00821985)
田中 創大  北海道大学, 工学研究院, 助教 (00826092)
清水 伸一  北海道大学, 医学研究院, 教授 (50463724)
Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2023: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2022: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2021: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2020: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2019: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Keywords放射線治療 / 粒子線治療 / 免疫治療 / 時空間分割照射 / 放射線生物学 / ヘリウム線治療 / 陽子線CT / 免疫放射線治療 / 4次元分割照射 / 陽子線 / ヘリウム線 / 免疫賦活照射 / 低LET / PD-1機能 / ヘリウム / PD-L1阻害 / PD-1 / 免疫賦活 / リアルタイム適合照射
Outline of Research at the Start

難治性の局所進行性肺がん等の治癒率を向上させるため、新小型超電導加速器によりヘリウムと陽子を同一治療装置で加速可能とし、治療計画精度を飛躍的に向上できる次世代型粒子線治療装置「陽子線CT搭載型ヘリウム・陽子線混合治療装置」を開発するための医学物理研究を行う。また、放射線のLETと細胞内活性酸素発現・ミトコンドリア分布・免疫チェックポイント阻害に関連する分子等の関係を明確にし、ヘリウム線が'免疫賦活照射法'として適しているかに関して小動物in vivoイメージングシステム等を用いて探求する。これらにより安全な局所制御のみならず、免疫賦活による生存率向上に最適な、次世代放射線治療法を追及する。

Outline of Final Research Achievements

A technology was devised to emit diagnostic (high-energy, low-intensity) beams in addition to the therapeutic beams from the particle therapy device in a short time to estimate the irradiation range in real time, control the energy, intensity and irradiation angle of the therapeutic beams using the estimated results, and deliver an accurate dose to the affected area in accordance with the treatment plan. A working hypothetical model of four-dimensional (spatiotemporal) segmented particle beam therapy for immunostimulation of living organisms was developed, and the model was fitted to the results of several previous animal experiments. A search was conducted for proteins that regulate changes in the spatial distribution of intracellular organelles as a radiation response in cancer cells, and several candidates were obtained, suggesting the possibility of a clue to the elucidation of the ‘post-irradiation recovery-power field.’

Academic Significance and Societal Importance of the Research Achievements

陽子線、ヘリウム線、炭素線などの粒子線治療における体内のリアルタイムな吸収線量分布を把握するために有用な新たな技術仕様が示すことができ、今後の画像誘導粒子線治療の一つの可能性を示した。放射線により、宿主側の免疫を賦活しつつ、がんを消失させるための作業仮説モデルが完成した。4次元分割照射をミクロンレベルで行うことが、細胞内小器官の空間分布の変化を制御するために意義があることが示唆され、さらに細胞内小器官の分布や活性酸素レベルの分布研究を進める意義が示された。

Report

(6 results)
  • 2024 Final Research Report ( PDF )
  • 2023 Annual Research Report
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (29 results)

All 2024 2021 2020 Other

All Int'l Joint Research (1 results) Journal Article (26 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 25 results,  Open Access: 22 results) Presentation (1 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Dept. of Radiation Oncology/Faculty of Medicine/Stanford University(米国)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Chest wall pain after single-fraction thoracic stereotactic ablative Radiotherapy: Dosimetric analysis from the iSABR trial2024

    • Author(s)
      Lau Brianna、Wu Yufan F.、Cui Sunan、Fu Jie、Jackson Scott、Pham Daniel、Dubrowski Piotr、Eswarappa Shaila、Skinner Lawrie、Shirato Hiroki、Taguchi Hiroshi、Gensheimer Michael F.、Gee Harriet、Chin Alexander L.、Diehn Maximilian、Loo Billy W.、Moiseenko Vitali、Vitzthum Lucas K.
    • Journal Title

      Radiotherapy and Oncology

      Volume: 196 Pages: 110317-110317

    • DOI

      10.1016/j.radonc.2024.110317

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A novel method for measurements of sleep/wake states, feeding and drinking behaviors using the tracking technique of 3D positions in freely moving mice2024

    • Author(s)
      Hamada Toshiyuki、Sutherland Kenneth、Ishikawa Masayori、Saito Jun、Miyamoto Naoki、Honma Sato、Shirato Hiroki、Honma Ken-ichi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 732 Pages: 150359-150359

    • DOI

      10.1016/j.bbrc.2024.150359

    • Related Report
      2023 Annual Research Report
    • Open Access
  • [Journal Article] Quality of life improvement after radiotherapy for bone metastases assessed using real-world data: a secondary analysis of a Nationwide Multicenter Cohort Study2024

    • Author(s)
      Utsumi Nobuko、.. Shirato Hiroki、et al.
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: 55 Issue: 2 Pages: 140-147

    • DOI

      10.1093/jjco/hyae150

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Health Utility of Pain Response Versus Nonresponse to Palliative Radiation Therapy for Symptomatic Bone Metastases: Analyses Based on Real-World Data from 26 Centers2024

    • Author(s)
      Saito Tetsuo、.. Shirato Hiroki、..et al.
    • Journal Title

      Journal of Palliative Medicine

      Volume: 28 Pages: 42-49

    • DOI

      10.1089/jpm.2024.0208

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The lipid‐binding D4 domain of perfringolysin O facilitates the active loading of exogenous cargo into extracellular vesicles2024

    • Author(s)
      Opadele Abayomi Emmanuel、Nishioka Soichiro、Wu Ping‐Hsiu、Le Quynh‐Thu、Shirato Hiroki、Nam Jin‐Min、Onodera Yasuhito
    • Journal Title

      FEBS Letters

      Volume: 598 Issue: 4 Pages: 446-456

    • DOI

      10.1002/1873-3468.14807

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Single-Institution Prospective Study To Evaluate the Safety and Efficacy of Real- Time Image-Gated Spot-Scanning Proton Therapy (RGPT) for Prostate Cancer2024

    • Author(s)
      Nishioka Kentaro、Hashimoto Takayuki、Mori Takashi、Uchinami Yusuke、Kinoshita Rumiko、Katoh Norio、Taguchi Hiroshi、Yasuda Koichi、Ito Yoichi M.、Takao Seishin、Tamura Masaya、Matsuura Taeko、Shimizu Shinichi、Shirato Hiroki、Aoyama Hidefumi
    • Journal Title

      Advances in Radiation Oncology

      Volume: 9 Issue: 5 Pages: 101464-101464

    • DOI

      10.1016/j.adro.2024.101464

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiparametric Analysis of Tumor Morphological and Functional MR Parameters Potentially Predicts Local Failure in Pharynx Squamous Cell Carcinoma Patients2021

    • Author(s)
      Fujima Noriyuki、Shimizu Yukie、Yoshida Daisuke、Kano Satoshi、Mizumachi Takatsugu、Homma Akihiro、Yasuda Koichi、Onimaru Rikiya、Sakai Osamu、Kudo Kohsuke、Shirato Hiroki
    • Journal Title

      The Journal of Medical Investigation

      Volume: 68 Issue: 3.4 Pages: 354-361

    • DOI

      10.2152/jmi.68.354

    • NAID

      130008115660

    • ISSN
      1343-1420, 1349-6867
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The role of endoscopic resection for selected patients with sinonasal squamous cell carcinoma2021

    • Author(s)
      Yuji Nakamaru, Masanobu Suzuki, Satoshi Kano, Takatsugu Mizumachi, Nayuta Tsushima, Takayoshi Suzuki, Aya Honma, Akira Nakazono, Shogo Kimura, Rikiya Onimaru, Koichi Yasuda, Hiroki Shirato, Akihiro Homma
    • Journal Title

      Auris Nasus Larynx

      Volume: 48 Issue: 1 Pages: 131-137

    • DOI

      10.1016/j.anl.2020.06.014

    • NAID

      120007189934

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Calibrated uncertainty estimation for interpretable proton computed tomography image correction using Bayesian deep learning2021

    • Author(s)
      Nomura Yusuke、Tanaka Sodai、Wang Jeff、Shirato Hiroki、Shimizu Shinichi、Xing Lei
    • Journal Title

      Physics in Medicine & Biology

      Volume: 66 Issue: 6 Pages: 065029-065029

    • DOI

      10.1088/1361-6560/abe956

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Period1 gene expression in the olfactory bulb and liver of freely moving streptozotocin-treated diabetic mouse2021

    • Author(s)
      Kanou H, Nagasawa K, Ishi Y, Chishima A, Hayashi J, Haga S, Sutherland K, Ishikawa M, Ozaki M, Shirato H, Hamada K, Hamada T
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 260 Pages: 14-20

    • DOI

      10.1016/j.bbrc.2021.04.049

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Fundamental study on quality assurance (QA) procedures for a real‐time tumor tracking radiotherapy (RTRT) system from the viewpoint of imaging devices2021

    • Author(s)
      Kimura Suguru、Miyamoto Naoki、Sutherland Kenneth L.、Suzuki Ryusuke、Shirato Hiroki、Ishikawa Masayori
    • Journal Title

      Journal of Applied Clinical Medical Physics

      Volume: 22 Issue: 7 Pages: 165-176

    • DOI

      10.1002/acm2.13307

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Validation of dose distribution for liver tumors treated with real-time-image gated spot-scanning proton therapy by log data based dose reconstruction2021

    • Author(s)
      Yamada Takahiro、Takao Seishin、Koyano Hidenori、Nihongi Hideaki、Fujii Yusuke、Hirayama Shusuke、Miyamoto Naoki、Matsuura Taeko、Umegaki Kikuo、Katoh Norio、Yokota Isao、Shirato Hiroki、Shimizu Shinichi
    • Journal Title

      Journal of Radiation Research

      Volume: 62 Issue: 4 Pages: 626-633

    • DOI

      10.1093/jrr/rrab024

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of target position from multiple fiducial markers by partial least squares regression in real-time tumor-tracking radiation therapy2021

    • Author(s)
      Ukon Kanako、Arai Yohei、Takao Seishin、Matsuura Taeko、Ishikawa Masayori、Shirato Hiroki、Shimizu Shinichi、Umegaki Kikuo、Miyamoto Naoki
    • Journal Title

      Journal of Radiation Research

      Volume: 62 Issue: 5 Pages: 926-933

    • DOI

      10.1093/jrr/rrab054

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of liver Dmean for proton beam therapy using deep learning and contour-based data augmentation2021

    • Author(s)
      Jampa-ngern Sira、Kobashi Keiji、Shimizu Shinichi、Takao Seishin、Nakazato Keiji、Shirato Hiroki
    • Journal Title

      Journal of Radiation Research

      Volume: -

    • DOI

      10.1093/jrr/rrab095

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Are simple verbal instructions sufficient to ensure that bladder volume does not deteriorate prostate position reproducibility during spot scanning proton therapy?2021

    • Author(s)
      Nishioka Kentaro、Gotoh Kento、Hashimoto Takayuki、Abe Takashige、Osawa Takahiro、Matsumoto Ryuji、Yokota Isao、Katoh Norio、Kinoshita Rumiko、Yasuda Koichi、Yakabe Toshiaki、Yoshimura Takaaki、Takao Seishin、Shinohara Nobuo、Aoyama Hidefumi、Shimizu Shinichi、Shirato Hiroki
    • Journal Title

      BJR|Open

      Volume: 3 Issue: 1

    • DOI

      10.1259/bjro.20210064

    • NAID

      120007171672

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Radiological tumour classification across imaging modality and histology2021

    • Author(s)
      Wu Jia、Li Chao、Gensheimer Michael、Padda Sukhmani、Kato Fumi、Shirato Hiroki、Wei Yiran、Schonlieb Carola-Bibiane、Price Stephen John、Jaffray David、Heymach John、Neal Joel W.、Loo Billy W.、Wakelee Heather、Diehn Maximilian、Li Ruijiang
    • Journal Title

      Nature Machine Intelligence

      Volume: 3 Issue: 9 Pages: 787-798

    • DOI

      10.1038/s42256-021-00377-0

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Potential benefits of adaptive intensity-modulated proton therapy in nasopharyngeal carcinomas.2021

    • Author(s)
      Minatogawa H, Yasuda K, Dekura Y, Takao S, Matsuura T, Yoshimura T, Suzuki R, Yokota I, Fujima N, Onimaru R, Shimizu S, Aoyama H, Shirato H.
    • Journal Title

      Journal of Applied Clinical Medical Physics

      Volume: 22 Issue: 1 Pages: 174-183

    • DOI

      10.1002/acm2.13128

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stability of D-luciferin for bioluminescence to detect gene expression in freely moving mice for long duration2021

    • Author(s)
      Nakajima K, Hamada K, Ito R, Yoshida Y, Sutherland K, Ishikawa M,Ozaki M, Shirato H, Hamada T
    • Journal Title

      The Journal of Biological and Chemical Luminescence

      Volume: 38 Issue: 1 Pages: 94-98

    • DOI

      10.1002/bio.3917

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rab27b contributes to radioresistance and exerts a paracrine effect via epiregulin in glioblastoma.2020

    • Author(s)
      Nishioka S, Wu PH, Yakabe T, Giaccia AJ, Le QT, Aoyama H, Shimizu S, Shirato H, Onodera Y, Nam JM.
    • Journal Title

      Neuro-Oncology Advances

      Volume: 8 Issue: 1 Pages: 1-13

    • DOI

      10.1093/noajnl/vdaa091

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quantitative analysis of treatments using real‐time image gated spot‐scanning with synchrotron‐based proton beam therapy system log data2020

    • Author(s)
      Yoshimura Takaaki、Shimizu Shinichi、Hashimoto Takayuki、Nishioka Kentaro、Katoh Norio、Taguchi Hiroshi、Yasuda Koichi、Matsuura Taeko、Takao Seishin、Tamura Masaya、Tanaka Sodai、Ito Yoichi M.、Matsuo Yuto、Tamura Hiroshi、Horita Kenji、Umegaki Kikuo、Shirato Hiroki
    • Journal Title

      Journal of Applied Clinical Medical Physics

      Volume: 21 Issue: 12 Pages: 10-19

    • DOI

      10.1002/acm2.13029

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lysosomal trafficking mediated by Arl8b and BORC promotes invasion of cancer cells that survive radiation.2020

    • Author(s)
      Wu PH, Onodera Y, Giaccia AJ, Le QT, Shimizu S, Shirato H, Nam JM.
    • Journal Title

      Communications Biology

      Volume: 27 Issue: 1 Pages: 1-15

    • DOI

      10.1038/s42003-020-01339-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Double recording system of Period1 gene expression rhythm in the olfactory bulb and liver in freely moving mouse2020

    • Author(s)
      Hamada K, Oota A, Ito R, Kasahara S,Nakajima K, Kikuchi K, Sutherland K, Ishikawa M,Shirato H, Ozaki M, Hamada T
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 529 Issue: 4 Pages: 898-903

    • DOI

      10.1016/j.bbrc.2020.05.224

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The impact of dose delivery time on biological effectiveness in proton irradiation with various biological parameters2020

    • Author(s)
      Kasamatsu Koki、Matsuura Taeko、Tanaka Sodai、Takao Seishin、Miyamoto Naoki、Nam Jin‐Min、Shirato Hiroki、Shimizu Shinichi、Umegaki Kikuo
    • Journal Title

      Medical Physics

      Volume: 47 Issue: 9 Pages: 4644-4655

    • DOI

      10.1002/mp.14381

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fast spot-scanning proton dose calculation method with uncertainty quantification using a three-dimensional convolutional neural network2020

    • Author(s)
      Nomura Yusuke、Wang Jeff、Shirato Hiroki、Shimizu Shinichi、Xing Lei
    • Journal Title

      Physics in Medicine & Biology

      Volume: 65 Issue: 21 Pages: 215007-215007

    • DOI

      10.1088/1361-6560/aba164

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dynamic gating window technique for the reduction of dosimetric error in respiratory-gated spot-scanning particle therapy: An initial phantom study using patient tumor trajectory data2020

    • Author(s)
      Naoki Miyamoto, Kouhei Yokokawa, Seishin Takao, Taeko Matsuura, Sodai Tanaka, Shinichi Shimizu, Hiroki Shirato, Kikuo Umegaki
    • Journal Title

      Journal of Applied Clinical Medical Physics

      Volume: 1 Issue: 4 Pages: 1-9

    • DOI

      10.1002/acm2.12832

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The updated outcomes of bladder-preserving trimodal therapy using a real-time tumor-tracking radiotherapy system for patients with muscle-invasive bladder cancer2020

    • Author(s)
      Miyata Haruka、Osawa Takahiro、Abe Takashige、Kikuchi Hiroshi、Matsumoto Ryuji、Maruyama Satoru、Nishioka Kentaro、Shimizu Shinichi、Hashimoto Takayuki、Shirato Hiroki、Shinohara Nobuo
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: - Issue: 5 Pages: 609-616

    • DOI

      10.1093/jjco/hyz211

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] A Phase II Trial of Individualized Stereotactic Ablative Radiotherapy for Lung Tumors (iSABR)2021

    • Author(s)
      MF Gensheimer, HE Gee, R Von Eyben, H Shirato, et al.
    • Organizer
      Annual Meeting of American Society for Radiation Oncology 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 治療計画装置、治療計画生成方法及びコンピュータプログラム2021

    • Inventor(s)
      高柳 泰介 , 山田 貴啓 , .. 白土 博樹 , 他
    • Industrial Property Rights Holder
      高柳 泰介 , 山田 貴啓 , .. 白土 博樹 , 他
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-057201
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report

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Published: 2019-04-18   Modified: 2026-01-16  

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