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Basic study of targeting cancer stem cells by heavy-ion beams and hyperthermia

Research Project

Project/Area Number 16K10341
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Radiation science
Research InstitutionGunma University

Principal Investigator

Takahashi Akihisa  群馬大学, 重粒子線医学推進機構, 教授 (60275336)

Research Collaborator ParK Seong-Joon  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords放射線科学 / 重粒子線 / ハイパーサーミア / がん幹細胞 / 感受性
Outline of Final Research Achievements

Targeting cancer stem cells (CSCs) might enable improvement of the cancer therapies. The overexpression of Lin28B reduced mature let-7 microRNA expression in melanoma cell lines, and enhanced the sphere-forming ability of melanoma cell lines, which is a characteristic of CSC populations. Interestingly, Lin28B-overexpressed melanoma cells were more resistant to X-ray irradiation than control cells, and Lin28B-induced radioresistance was abolished after carbon ion irradiation. Our results suggest that a carbon ion beam is more effective than an X-ray beam in terms of killing cancer cells, possibly due to elimination of CSC populations.
In addition, we demonstrated that C-ion and heat treatment can induce DNA damage via DSB formation reflected by γH2AX foci formation under hypoxia. C-ion and yperthermia therapy can be beneficial for the prognosis of cancer patients through increased DNA damage leading to tumor cell death.

Academic Significance and Societal Importance of the Research Achievements

従来、「がん幹細胞」は細胞表面マーカーを指標としていたが、それらは数多く存在し。さらに、細胞表面マーカーは一過性に増減するものの、細胞集団内での陽性頻度が一定に保たれていることが報告されており、がん幹細胞化に果たす役割は不明な点が多かった。その点、我々が利用したLin28未分化誘導経路を遺伝子操作したがん細胞を用いることは、本質的な「がん幹細胞」を捉えられる点が学術的な特色があったと言えるだろう。
また、従来のX線治療で抵抗性を示した低酸素分画において、重粒子線と温熱による効率的なDNA損傷生成を確認し、重粒子線と温熱治療のアドバンテージを示す結果を得た。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (19 results)

All 2018 2017 2016 Other

All Int'l Joint Research (3 results) Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (2 results) Remarks (1 results)

  • [Int'l Joint Research] DIRAMS(韓国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] University of South Calorina(米国)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] DIRAMS(韓国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Formation Mechanism and Cellular Functions of Nuclear Stress Bodies Induced by Heat Stress2018

    • Author(s)
      Yuichi Miyoshi, Kazunori Watanabe
    • Journal Title

      Thermal Medicine

      Volume: 34 Issue: 3 Pages: 23-34

    • DOI

      10.3191/thermalmed.34.23

    • NAID

      130007520470

    • ISSN
      1882-2576, 1882-3750
    • Year and Date
      2018-09-15
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] BRCA2 protects mammalian cells from heat shock2018

    • Author(s)
      Yosuke Nakagawa, Atsuhisa Kajihara, Akihisa Takahashi, Akiho S. Murata, Masaya Matsubayashi, Soichiro S. Ito, Ichiro Ota, Takahiko Nakagawa, Masatoshi Hasegawa, Tadaaki Kirita, Takeo Ohnishi, Eiichiro Mori
    • Journal Title

      Int J Hyperthermia

      Volume: 印刷中 Issue: 6 Pages: 1-7

    • DOI

      10.1080/02656736.2017.1370558

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Homologous recombination preferentially repairs heat-induced DNA double-strand breaks in mammalian cells2016

    • Author(s)
      Akihisa Takahashi, Eiichiro Mori, Yosuke Nakagawa, Atsuhisa Kajihara, Tadaaki Kirita, Douglas L. Pittman, Masatoshi Hasegawa, Takeo Ohnishi
    • Journal Title

      Int J Hyperthermia

      Volume: 13 Issue: 3 Pages: 1-7

    • DOI

      10.1080/02656736.2016.1252989

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 低酸素環境下における温熱誘導DNA二本鎖切断の生成2018

    • Author(s)
      吉田由香里, 富永信太朗, 高橋昭久
    • Organizer
      第22回関東ハイパーサーミア研究会・全身ハイパーサーミア研究会合同学術研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] X線と重粒子線によるDNA二本鎖切断生成の酸素濃度依存性2018

    • Author(s)
      富永 信太朗, 吉田 由香里, 高橋 昭久
    • Organizer
      第55回群馬放射線腫瘍研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] Effects of oxygen concentration and radiation quality on radiation-induced DNA damage2017

    • Author(s)
      Shintaro Tominaga, Hiroko Okada, Hiroko Ikeda, Yukari Yoshida, Akihisa Takahashi
    • Organizer
      第7回国際放射線神経生物科学会
    • Place of Presentation
      ホテル双葉, 越後湯沢
    • Year and Date
      2017-02-09
    • Related Report
      2016 Research-status Report
  • [Presentation] 炭素線によるがん治療効果向上ための基礎研究成果~ DNA修復と細胞周期調節の阻害剤による炭素線の増感効果~2017

    • Author(s)
      髙橋 昭久
    • Organizer
      第19回癌治療増感研究シンポジウム
    • Place of Presentation
      奈良県文化会館, 奈良
    • Year and Date
      2017-02-03
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] HR修復およびNHEJ修復阻害剤による炭素線増感効果の検討2017

    • Author(s)
      高橋昭久、吉田由香里、金井達明、大野達也、馬洪玉、中川彰子、中野隆史、舟山知夫、小林泰彦
    • Organizer
      第1回QST高崎研シンポジウム
    • Place of Presentation
      量研機構・高崎研, 高崎
    • Year and Date
      2017-01-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 腫瘍内微小環境における温熱誘導DNA二本鎖切断2017

    • Author(s)
      高橋昭久,瀬下幸彦,富永信太朗,安達彰子,原田浩,吉田由香里
    • Organizer
      日本ハイパーサーミア学会第34回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] マウス移植腫瘍における温熱誘導DNA二本鎖切断2017

    • Author(s)
      髙橋 昭久, 瀬下幸彦, 安達彰子, 吉田由香里
    • Organizer
      第21回関東ハイパーサーミア研究会・全身ハイパーサーミア研究会合同学術研究会
    • Place of Presentation
      東海大学校友会館, 東京
    • Related Report
      2016 Research-status Report
  • [Presentation] 温熱によるDNA二本鎖切断は相同組換えで修復される2016

    • Author(s)
      髙橋 昭久, 森 英一朗, 仲川 洋介, 梶原 淳久, 桐田 忠昭, 大西 武雄,
    • Organizer
      日本ハイパーサーミア学会第33回大会
    • Place of Presentation
      つくば国際会議場, 筑波
    • Year and Date
      2016-09-02
    • Related Report
      2016 Research-status Report
  • [Presentation] Enhancement of heat sensitivity of human cancer cells by inhibitor of HR but not NHEJ2016

    • Author(s)
      Akihisa Takahashi, Eiichiro Mori, Atsuhisa Kajihara, Yosuke Nakagawa, Takeo Ohnishi
    • Organizer
      2016 International Congress of Hyperthermic Oncology
    • Place of Presentation
      New Orlens, LA
    • Year and Date
      2016-04-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] The role of Lin28/let7 axis as a target for radiosensitization of melanoma cancer cells2016

    • Author(s)
      Seong-Joon Park, Akihisa Takahashi
    • Organizer
      第22回癌治療増感研究会
    • Place of Presentation
      沖縄県市町村自治会館, 那覇
    • Related Report
      2016 Research-status Report
    • Invited
  • [Book] Molecular damage: Hyperthermia alone. "Hyperthermic Oncology from Bench to Besides"2016

    • Author(s)
      Takahashi A
    • Total Pages
      14
    • Publisher
      Springer
    • Related Report
      2016 Research-status Report
  • [Book] Inhibition of DNA repair system activity. "Hyperthermic Oncology from Bench to Besides"2016

    • Author(s)
      Takahashi A
    • Total Pages
      17
    • Publisher
      Springer
    • Related Report
      2016 Research-status Report
  • [Remarks] http://heavy-ion.showa.gunma-u.ac.jp/lab/

    • Related Report
      2017 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2022-02-22  

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