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Elucidation of radioresistance mechanisms in cancer stem cells focusing on mTOR activation under hypoxic/nutrient starvation conditions

Research Project

Project/Area Number 26860974
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Radiation science
Research InstitutionTohoku University

Principal Investigator

Murata Yasuhiko  東北大学, 医学系研究科, 助教 (40716172)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsmTOR / 低酸素状態 / 低栄養状態 / 放射線抵抗性 / 癌肝細胞 / PLDR / 癌幹細胞 / 低栄養 / 低酸素
Outline of Final Research Achievements

The presence of radiation resistant cells in solid human tumors is one of the most important factors for radiotherapy. In solid human tumors, it is well known that hypoxia causes cellular radioresistance and that tumor hypoxia is consistently associated with nutrient starvation conditions. To identify molecular targets for selective regulation of radioresistance under hypoxic/nutrient starvation conditions, mTOR, known as nutrient sensor, was focused. Under nutrient starvation conditions, mTOR activity is thought to be inhibited and cells show radioresistance. Liver cancer cell lines, however, showed that mTOR activation and increased radiosensitivity under nutrient starvation conditions. Inhibition of mTOR expression by siRNA suppresses the increased radiosensitivity under nutrient starvation conditions. This study demonstrates for the first time that nutrient starvation conditions activate mTOR and increase radiosensitivity through mTOR activation in liver cancer cell lines.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (11 results)

All 2016 2015 2014

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (8 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] NSAIDs diclofenac, indomethacin, and meloxicam highly upregulate expression of ICAM-1 and COX-2 induced by X-irradiation in human endothelial cells2016

    • Author(s)
      Y Uehara, Y Murata, S Shiga, Y Hosoi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 479 Issue: 4 Pages: 847-852

    • DOI

      10.1016/j.bbrc.2016.09.120

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation of mTORC1 under nutrient starvation conditions increases cellular radiosensitivity in human liver cancer cell lines, HepG2 and HuH6.2015

    • Author(s)
      Yasuhiko Murata, Yoshihiko Uehara, Yoshio Hosoi
    • Journal Title

      Biochimical and Biophysical Research Communications

      Volume: 468 Issue: 4 Pages: 684-690

    • DOI

      10.1016/j.bbrc.2015.11.016

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Enhanced survival of mice infused with bone marrow-derived as compared with adipose-derived mesenchymal stem cells.2014

    • Author(s)
      Shiratsuki S, Terai S, Murata Y, Takami T, Yamamoto N, Fujisawa K, Burganova G, Quintanilha LF, Sakaida I.
    • Journal Title

      Hepatol Res

      Volume: - Issue: 13 Pages: 1353-1359

    • DOI

      10.1111/hepr.12507

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 低栄養状態のヒト肝癌細胞におけるmTORC1の活性化による放射線感受性の増加2016

    • Author(s)
      村田泰彦、上原芳彦、細井義夫
    • Organizer
      第45回制癌シンポジウム第54回生物部会学術大会
    • Place of Presentation
      I-siteなんば(大阪府大阪市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヒト肝癌細胞における低栄養状態によるmTORC1の活性化は放射線感受性を増加させる2016

    • Author(s)
      村田泰彦、上原芳彦、細井義夫
    • Organizer
      日本放射線影響学会第59回大会
    • Place of Presentation
      JMSアステールプラザ(広島県広島市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Effects of nutrient starvation condition on radiosensitivity of cultured cells.2015

    • Author(s)
      Yasuhiko Murata, Yoshihiko Uehara, Yoshio Hosoi
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      Kyoto International Conference Center, Kyoto, Japan
    • Year and Date
      2015-05-27
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Synergistic effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and ionizing radiation on ICMA-1 expression in HUVECs.2015

    • Author(s)
      Yoshihiko Uehara, Yasuhiko Murata, Yoshio Hosoi
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      Kyoto International Conference Center, Kyoto, Japan
    • Year and Date
      2015-05-26
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 低栄養状態が培養細胞の放射線感受性に及ぼす影響2015

    • Author(s)
      村田泰彦、上原芳彦、細井義夫
    • Organizer
      第17回癌治療増感研究シンポジウム
    • Place of Presentation
      奈良県文化会館(奈良市)
    • Year and Date
      2015-02-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 非ステロイド抗炎症性薬は放射線と相乗的に作用してヒト血管内皮細胞におけるICAM-1の発現を亢進させる2014

    • Author(s)
      上原芳彦、村田泰彦、細井義夫
    • Organizer
      日本放射線影響学会第57回大会
    • Place of Presentation
      かごしま県民交流センター(鹿児島市)
    • Year and Date
      2014-10-03
    • Related Report
      2014 Research-status Report
  • [Presentation] 低栄養状態が培養細胞の放射線感受性に及ぼす影響2014

    • Author(s)
      村田泰彦、上原芳彦、細井義夫
    • Organizer
      日本放射線影響学会第57回大会
    • Place of Presentation
      かごしま県民交流センター(鹿児島市)
    • Year and Date
      2014-10-03
    • Related Report
      2014 Research-status Report
  • [Presentation] 低栄養が放射線感受性に及ぼす影響2014

    • Author(s)
      村田泰彦、上原芳彦、細井義夫
    • Organizer
      第43回制癌シンポジウム第52回生物部会学術大会
    • Place of Presentation
      メルパルク京都(京都市)
    • Year and Date
      2014-07-12
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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