Research for local and systemic response of BNCT and identification of biomarkers related to its efficacy and side effects

• Project/Area Number: 18H02693
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Nagasaki University
• Principal Investigator: Masutani Mitsuko 長崎大学, 医歯薬学総合研究科(医学系), 教授 (60238904)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2021: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
• Keywords: BNCT / 中性子 / バイオマーカー / HMGB1 / プロテオーム / DAMPs / 中性子線 / マウスモデル / メラノーマ

Outline of Final Research Achievements

BNCT (boron neutron capture therapy) is a selective radiation therapy for cancer cells that utilizes boron carrier drugs targeting cancer cells. Particle beams including alpha ray with short path cause selective killing of cancer cells in BNCT. In this study, we carried out research for identification of local and systemic biomarkers for early response of BNCT. Using transcriptome and proteome and other analyses, we found multiple biomarker candidate molecules including HMGB1, which show an early extracellular release and release in blood in a mouse xenograft model.

Academic Significance and Societal Importance of the Research Achievements

BNCTの大きな課題の一つとして、効果や副作用を早期に予測、判定することが難しいことである。BNCTが効果を得るには、薬剤の腫瘍部位への到達、中性子線照射の詳細な測定が必要だが、これらの照射中の測定は未だ困難である。
本研究で見いだしたHMGB1などのBNCT後の早期応答に関する複数の候補因子はBNCTの治療の奏効性や副作用と関連するバイオマーカーとしても有用な基盤的資料となると考えられる。

Research Products

• [Int'l Joint Research] National Council of Research (ITB-CNR)(イタリア)
• [Int'l Joint Research] University of Leipzig(ドイツ)
• [Int'l Joint Research] National Council of Research (ITB-CNR)(イタリア)
• [Int'l Joint Research] University of Leipzig(ドイツ)
• [Journal Article] Analysis of the response of tumor tissue and cells to BNCT (2020)
  • Author(s): S. Imamichi, L. Chen, M. Ihara, N. Toriya, Y. Mitsuhashi, T. Onodera, Y. Sasaki, Y. Sanada, S. Masunaga and M. Masutani
  • Journal Title: KURNS Progress Report 2019 Volume: - Pages: 71-71
  • Open Access
• [Journal Article] Analysis of the response of tumor and normal tissues to BNCT. (2020)
  • Author(s): S. Imamichi, L. Chen, M. Ihara, Y. Sasaki, Takae Onodera, Y. Natori, N. Toriya, A. Takahira J. Itami, S. Masunaga and M. Masutani.
  • Journal Title: KURRI Progress Report 2018 Volume: in press
  • Open Access
• [Presentation] Increase of HMGB1 level released from cancer cells after BNCT irradiation and its role in the radiation response. (2020)
  • Author(s): S. Imamichi, Lichao Chen, Tong Ying, Yuka Sasaki, Takae Onodera, Minoru Suzuki, Shinichiro Masunaga , Mitsuko Masutani.
  • Organizer: 第79回日本癌学会学術総会
• [Presentation] The roles of GM-CSF and inflammatory/immune cascades in the tumor cell response to boron neutron capture therapy (BNCT). (2020)
  • Author(s): Lichao Chen, S. Imamichi, Tong Ying, Yuka Sasaki, Takae Onodera, S Masunaga, M. Masutani.
  • Organizer: 第79回日本癌学会学術総会
• [Presentation] 加速器型ホウ素中性子捕捉療法 (BNCT）の生物研究と動向 (2020)
  • Author(s): 益谷美都子
  • Organizer: QMFライフサイエンス研究会
  • Invited
• [Presentation] Evaluation of the biological effectiveness in cells and mice for BNCT system in National Cancer Center Hospital (2019)
  • Author(s): Shoji Imamichi, Satoshi Nakamura, Yuka Sasaki, Chen Lichao, Takae Onodera, Makoto Ihara, Hiroyuki Okamoto, Yoshihisa Abe, Kenji Sshimada, Masaru Nakamura, Yoshio Imahori, Jun Itami, Mitsuko Masutani.
  • Organizer: ICRR 2019
  • Int'l Joint Research
• [Presentation] A clinical trial of lithium-targeted accelerator-based boron neutron capture therapy at National Cancer Center Hospital. (2019)
  • Author(s): Hiroshi Igaki, Satoshi Nakamura, Shoji Imamichi, Mitsuko Masutani, and Jun Itami et al.
  • Organizer: yBNCT10
  • Int'l Joint Research
• [Presentation] がん細胞におけるホウ素中性子捕捉反応後の早期の遺伝子発現変動の解析 (2019)
  • Author(s): 鳥谷直紀、今道祥二、Chen, Lichao、 名取 宥哉、佐々木由香、小野寺貴恵、前田祐斗、井原 誠、真田 悠生、中村哲志、伊丹 純、増永慎一郎、益谷美都子
  • Organizer: 第16回日本中性子捕捉療法学会学術大会
• [Presentation] Biological evaluation of the BNCT system in National Cancer Center Hospital using cells and mice (2019)
  • Author(s): Shoji Imamichi, Yuka Sasaki, Makoto Ihara, Takae Onodera, Chen Lichao, Satoshi Nakamura, Hiroyuki Okamoto, Yoshio Imahori, Jun Itami, Mitsuko Masutani.
  • Organizer: 第16回日本中性子捕捉療法学会学術大会
• [Presentation] The roles of GM-CSF in the response of cancer cells after BNCT (2019)
  • Author(s): Lichao Chen, Shoji Imamichi, Takae Onodera, Yuka Sasaki, Makoto Ihara, Yu Sanada, Satoshi Nakamura, Jun Itami, Shinichiro Masunaga, Mitsuko Masutani.
  • Organizer: 第16回日本中性子捕捉療法学会学術大会
• [Book] Proteomic Investigations for BNCT. chapter 22 Neutron Capture Therapy, Second Edition (2020)
  • Author(s): Mitsuko Masutani, PierLuigi Mauri
  • Publisher: Springer Nature
• [Book] Proteomic Investigations for BNCT chapter 22, Neutron Capture Therapy, Second Edition_Chapter (2020)
  • Author(s): Mitsuko Masutani, PierLuigi Mauri
  • Publisher: Springer Nature