Analysis of cancer cell dynamics after proton irradiation using real-time imaging

• Project/Area Number: 19K17175
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Aichi Cancer Center Research Institute (2022); Nagoya City University (2019-2021)
• Principal Investigator: Hashimoto Shingo 愛知県がんセンター(研究所), 分子腫瘍学分野, 研究員 (90803510)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 陽子線 / X線 / DNA二本鎖切断 / γH2AX / 遊走能 / 浸潤能 / スクラッチ / 増感効果 / リアルタイムイメージング

Outline of Research at the Start

リアルタイムイメージング装置を活用し、生体内環境に近似した細胞培養下において、陽子線照射後の癌細胞動態（細胞遊走能・浸潤能）をX線照射後と比較することで評価する。

Outline of Final Research Achievements

Experiments were performed on cultured cells using X-ray and proton beam. In this study, the migration ability after irradiation experiments was examined using time-lapse images, and no significant difference could be shown. On the other hand, it was suggested that the migration ability may differ transiently depending on the irradiation dose and the type of beam. Proton beam have the characteristic of low dose exposure at the proximal end and high dose exposure at the distal end, and may have different cellular effects at the proximal and distal ends. Although γH2AX is often used to predict cell viability, the optimal timing of the evaluation in the low-dose range is unknown and needed to be investigated. The optimal timing of γH2AX evaluation for cell viability prediction after low (10 mGy) to high (4000 mGy) doses of X-rays was 12 hours after irradiation.

Academic Significance and Societal Importance of the Research Achievements

陽子線は一つのビームの中で近位端の低線量被曝領域と遠位端の高線量被曝領域が混在しているという物理的な特性をもつ。10~4000mGy領域におけるX線照射後の細胞生存率予測に最適なγH2AX評価タイミングを確立することができた。これを用いて低線量被曝領域と高線量被曝領域における陽子線とX線の放射線生物学的な効果の推定につなげていくことができ、陽子線治療の最適な治療指針の確立という目的に向けて有意義なものと考えられる。

Research Products

• [Journal Article] Optimal timing of a γH2AX analysis to predict cellular lethal damage in cultured tumor cell lines after exposure to diagnostic and therapeutic radiation doses (2023)
  • Author(s): Takano Seiya、Shibamoto Yuta、Wang Zhen、Kondo Takuhito、Hashimoto Shingo、Kawai Tatsuya、Hiwatashi Akio
  • Journal Title: Journal of Radiation Research Volume: 64 Issue: 2 Pages: 317-327
  • DOI: 10.1093/jrr/rrac096
  • Peer Reviewed / Open Access
• [Journal Article] Outcomes of proton therapy for non-small cell lung cancer in patients with interstitial pneumonia (2022)
  • Author(s): Shingo Hashimoto, Hiromitsu Iwata, Yukiko Hattori, Koichiro Nakajima, Kento Nomura, Kensuke Hayashi, Toshiyuki Toshito, Eiko Yamamori, Kenji Akita, Jun-etsu Mizoe, Hiroyuki Ogino, Yuta Shibamoto
  • Journal Title: Radiation Oncology Volume: 17 Issue: 1 Pages: 56-56
  • DOI: 10.1186/s13014-022-02027-0
  • Peer Reviewed / Open Access
• [Presentation] 放射線照射後のDNA二本鎖切断の定量タイミングが細胞生存率予測に及ぼす影響 (2022)
  • Author(s): 高野聖矢、芝本雄太、王禎、近藤拓人、橋本眞吾、河合辰哉、樋渡昭雄
  • Organizer: 日本放射線腫瘍学会第35回学術大会
• [Presentation] Outcomes of Proton Therapy for Non-small Cell Lung Cancer in Patients with Interstitial Pneumonia (2020)
  • Author(s): 橋本眞吾
  • Organizer: 2020 ASTRO annual meeting
  • Int'l Joint Research