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Development of new radiation sensitization therapy by drug repositioning of chloroquine

Research Project

Project/Area Number 18K07771
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionKeio University

Principal Investigator

SHIGEMATSU Naoyuki  慶應義塾大学, 医学部(信濃町), 教授 (30178868)

Co-Investigator(Kenkyū-buntansha) 深田 淳一  慶應義塾大学, 医学部(信濃町), 講師 (50338159)
公田 龍一  慶應義塾大学, 医学部(信濃町), 助教 (00464834)
小池 直義  慶應義塾大学, 医学部(信濃町), 助教 (60464913)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords放射線生物学 / 膵癌 / 放射線抵抗性 / オートファジー / 放射線増感剤 / 膵臓癌 / クロロキン / 放射線照射 / 増感剤 / ドラッグリポジショニング
Outline of Final Research Achievements

As a treatment method for pancreatic cancer, which is an intractable malignant tumor, we focused on radiation resistance by autophagy and searched for the radiosensitizing effect of chloroquine drug repositioning. Pancreatic cancer cells were used to form spheroids, which were irradiated and administered with chloroquine in both normal medium and undernutrition, but there was no significant change in survival rate or size due to chloroquine, and no radiation sensitizing effect was observed.Moreover, the autophagy inhibitory effect was not clear. However, another study suggested an inhibitory effect on mitochondrial autophagy, mitophagy.

Academic Significance and Societal Importance of the Research Achievements

膵癌の多くは切除不能であり、放射線治療抵抗性で予後不良であることから放射線増感効果に着目した抗腫瘍効果の増強を探索する試みは重要と考える。オートファジーに着目した放射線増感剤の探索、機序解明を進めることで、放射線生物学的にも重要な研究と考えている。
本研究ではクロロキンによる増感効果、オートファジー阻害効果を明らかにすることはできなかったが、マイトファジーの阻害作用が示唆された。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (8 results)

All 2020 2019 2018

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (3 results)

  • [Journal Article] 2-Nitroimidazoles induce mitochondrial stress and ferroptosis in glioma stem cells residing in a hypoxic niche2020

    • Author(s)
      Koike Naoyoshi、Kota Ryuichi、Naito Yoshiko、Hayakawa Noriyo、Matsuura Tomomi、Hishiki Takako、Onishi Nobuyuki、Fukada Junichi、Suematsu Makoto、Shigematsu Naoyuki、Saya Hideyuki、Sampetrean Oltea
    • Journal Title

      Communications Biology

      Volume: 3 Issue: 1 Pages: 450-462

    • DOI

      10.1038/s42003-020-01165-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Efficacy evaluation of 2D, 3D U-Net semantic segmentation and atlas-based segmentation of normal lungs excluding the trachea and main bronchi.2020

    • Author(s)
      Nemoto T, Futakami N, Yagi M, Kumabe A, Takeda A, Kunieda E, Shigematsu N.
    • Journal Title

      J Radiat Res

      Volume: 61(2) Issue: 2 Pages: 257-264

    • DOI

      10.1093/jrr/rrz086

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pleural contact decreases survival in clinical T1N0M0 lung cancer patients undergoing SBRT.2019

    • Author(s)
      Eriguchi T, Takeda A, Tsurugai Y, Sanuki N, Kibe Y, Hara Y, Kaneko T, Taguri M, Shigematsu N.
    • Journal Title

      Radiother Oncol

      Volume: 134 Pages: 191-198

    • DOI

      10.1016/j.radonc.2019.02.005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Highly Advanced Gastric Cancer Maintaining a Clinical Complete Response after Chemoradiotherapy Comprising S-1 and Cisplatin2018

    • Author(s)
      Yura Masahiro、Takahashi Tsunehiro、Fukuda Kazumasa、Nakamura Rieko、Wada Norihito、Fukada Junichi、Kawakubo Hirofumi、Takeuchi Hiroya、Shigematsu Naoyuki、Kitagawa Yuko
    • Journal Title

      Case Reports in Gastroenterology

      Volume: 12 Issue: 3 Pages: 578-585

    • DOI

      10.1159/000492206

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prostate-specific antigen nadir within 12 months as an early surrogate marker of biochemical failure and distant metastasis after low-dose-rate brachytherapy or external beam radiotherapy for localized prostate cancer.2018

    • Author(s)
      Nishimura S, Ohashi T, Momma T, Sakayori M, Eriguchi T, Tanaka T, Yamashita S, Kosaka T, Oya M, Shigematsu N
    • Journal Title

      Cancer Med

      Volume: 7 Issue: 5 Pages: 1794-1801

    • DOI

      10.1002/cam4.1443

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 機械学習による胸部放射線照射後の予後予測因子と有害事象発症予測因子の探索2020

    • Author(s)
      深田淳一、深田恭平、小池直義、公田龍一、茂松直之
    • Organizer
      第58回日本癌治療学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 放射線照射後のマウス心臓の形態学的・病理学的検討2019

    • Author(s)
      小池直義、深田淳一、公田龍一、伊藤章吾、湯浅慎介、茂松直之
    • Organizer
      日本放射線腫瘍学会第32回学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] マウス放射線肺臓炎モデルにおける病理学的検討2019

    • Author(s)
      公田龍一、小池直義、深田淳一、茂松直之
    • Organizer
      日本放射線腫瘍学会第32回学術大会
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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