• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Basic Research on Gastrointestinal Cancer Stem Cell Targeting Therapy with Heavy Ion Beams

Research Project

Project/Area Number 24591858
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Radiation science
Research InstitutionNational Institute of Radiological Sciences

Principal Investigator

SAI SEI  独立行政法人放射線医学総合研究所, 重粒子医科学センター, 主任研究員 (20342735)

Co-Investigator(Kenkyū-buntansha) KAMIJO Takehiko  埼玉県立がんセンター, 臨床腫瘍研究所, 所長 (90262708)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords粒子線生物学 / 膵臓がん / がん幹細胞 / DNA損傷と修復 / 分子病理学 / 炭素線 / 膵臓癌 / 癌幹細胞 / 細胞生存率 / DNA損傷 / 治癒率 / 重粒子
Outline of Final Research Achievements

To elucidate whether a carbon ion beam in combination with gemcitabine has advantages over X-ray in targeting putative pancreatic cancer stem-like cells (CSCs) in vitro and in vivo. The number of colonies and spheroids formed from CSCs after carbon ion beam was significantly reduced compared to after X-ray irradiation, and they were extremely highly suppressed when carbon ion beam combined with gemcitabine. Expressions of multiple cell death-related genes were remarkably highly induced, and large numbers of γH2AX foci in CSCs were formed after carbon ion beam combined with gemcitabine. The highly expressed CSC markers were significantly inhibited after 30 Gy of carbon ion beam and almost lost after 25 Gy carbon ion beam combined with 50 mg/kg gemcitabine. In conclusion, a carbon ion beam combined with gemcitabine has superior potential to kill pancreatic CSCs via irreparable clustered DSB compared to a carbon ion alone or X-rays combined with gemcitabine.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (41 results)

All 2015 2014 2013 2012

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (35 results) (of which Invited: 9 results)

  • [Journal Article] Combination of Carbon Ion Beam and Gemcitabine Causes Unreparable DNA Damage and Death of Radioresistant Pancreatic Cancer Stem-Like Cells In Vitro and In Vivo2015

    • Author(s)
      Sai S, Wakai T, Vares G, Yamada S, Kamijo T, Kamada T, and Shirai T. Combination of Carbon Ion Beam and Gemcitabine Causes Unreparable DNA Damage and Death of Radioresistant Pancreatic Cancer Stem-Like Cells In Vitro and In Vivo
    • Journal Title

      Oncotarget

      Volume: 6 Pages: 5517-5535

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Progesterone generates cancer stem cells through membrane progesterone receptor-triggered signaling in basal-like human mammary cells2015

    • Author(s)
      Vares G, Sai S, Wang B, Fujimori A, Nenoi M, Nakajima T.
    • Journal Title

      Cancer Letter

      Volume: 362 Issue: 2 Pages: 167-173

    • DOI

      10.1016/j.canlet.2015.03.030

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The complexity of DNA double strand break is a crucial factor for activating ATR signaling pathway for G2/M checkpoint regulation regardless of ATM function.2015

    • Author(s)
      Xue L, Furusawa Y, Okayasu R, Miura M, Cui X et al.
    • Journal Title

      DNA Repair

      Volume: 25 Issue: 3 Pages: 72-83

    • DOI

      10.1104/pp.114.255430

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Arsenite induces premature senescence via p53/p21 pathway as a result of DNA damage in human malignant glioblastoma cells.2014

    • Author(s)
      Ninomiya Y, Cui X*, Yasuda T, Wang B, Yu D, Suzuki-Sekine E, and Nenoi M.
    • Journal Title

      BMB Reports

      Volume: 6

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Generation of breast cancer stem cells by steroid hormones in irradiated human mammary cell lines.2013

    • Author(s)
      Vares G, Cui X, Wang B, Nakajima T, Nenoi M.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 10 Pages: e77124-e77124

    • DOI

      10.1371/journal.pone.0077124

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Different effects of carbon ion beams and X-rays on clonogenic survival and DNA repair in human pancreatic cancer stem-like cells.2012

    • Author(s)
      Oonishi K, Cui X, Hirakawa H, Fujimori A, Kamiio T, Yamada S, Yokosuka O, Kamada T.
    • Journal Title

      Radiother Oncol.

      Volume: 105 Issue: 2 Pages: 258-265

    • DOI

      10.1016/j.radonc.2012.08.009

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 放射線抵抗性癌幹細胞に対する重粒子線単独或は抗癌剤との併用による細胞生存、DNA損傷、腫瘍抑制効果について2015

    • Author(s)
      崔星
    • Organizer
      第57回日本放射線影響学会
    • Place of Presentation
      鹿児島
    • Year and Date
      2015-10-01 – 2015-10-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Pancreatic Cancer Stem-Like Cell Targeting Radiotherapy by Carbon Ion Beam Alone or in Combination with Gemcitabine2015

    • Author(s)
      Sei Sai and Toshiyuki Shirai
    • Organizer
      Korea Society of Radiation Bioscience (KSRB) Spring Conference
    • Place of Presentation
      Busan, Korea
    • Year and Date
      2015-05-07 – 2015-05-08
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Combination of Carbon Ion Beam and Gemcitabine Causes Unrepairable DNA Damage and Death of Radioresistant Pancreatic Cancer Stem-Like Cells In Vitro and In Vivo2015

    • Author(s)
      Sei Sai, Toshifumi Wakai, Guillaume Vares, Shigeru Yamada, Tadashi Kamada, and Toshiyuki Shirai
    • Organizer
      AACR annual meeting
    • Place of Presentation
      Philadelphia, USA
    • Year and Date
      2015-04-18 – 2015-04-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] 炭素線とCisplatinとの併用によるTriple Negative乳癌幹細胞に対する細胞殺傷及びDNA損傷増感作用2015

    • Author(s)
      崔星、唐澤久美子、堀本義哉、林光弘、白井敏之
    • Organizer
      第17回癌治療増感シンポジウム
    • Place of Presentation
      奈良
    • Year and Date
      2015-02-06 – 2015-02-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 肝癌幹細胞に対する重粒子単独或はSorafenibとの併用による殺傷効果2014

    • Author(s)
      崔星、若井俊文、上條岳彦、白井敏之
    • Organizer
      第27回日本放射線腫瘍学会
    • Place of Presentation
      横浜
    • Year and Date
      2014-12-11 – 2015-12-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] ARTEMIS欠損によるヒト大腸癌幹細胞マーカー発現変化及びX線、炭素線に対する感受性増強2014

    • Author(s)
      崔星、上條岳彦、若井俊文、白井敏之
    • Organizer
      第73回日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 重粒子単独或はCisplatinとの併用によるTriple Negative乳癌幹細胞に対する細胞生存及びDNA損傷2014

    • Author(s)
      崔星、唐澤久美子、堀本義哉、林光弘、白井敏之
    • Organizer
      第22回日本乳癌学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-07-10 – 2014-07-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] arbon Ion Beam Combined with Gemcitabine Remarkably Disrupts Pancreatic Cancer Stem-Like Cells via Complex DNA Double Strand Breaks (DSB) and Multiple Cell Death Pathways2014

    • Author(s)
      Sei Sai and Toshiyuki Shirai
    • Organizer
      46th Annual Meeting of the European Pancreatic Club
    • Place of Presentation
      Southampton, UK
    • Year and Date
      2014-06-25 – 2014-06-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cancer Stem Cell-Targeting Radiotherapy by Carbon Ion Beam Alone or in Combination with Molecular Targeting Drugs2014

    • Author(s)
      Sei Sai and Toshiyuki Shirai
    • Organizer
      The 2nd Global Chinese Congress of Radiation Research (GCCRR2014)
    • Place of Presentation
      Suzhou, China
    • Year and Date
      2014-05-11 – 2015-05-15
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Effects of Carbon Ion Beam Alone or in Combination with Cisplatin on Triple Negative Breast Cancer Stem-Like Cells2014

    • Author(s)
      2.Sei Sai, Kumiko Karasawa, Guillaume Vares, Yoshiya Horimoto, Mitsuhiro Hayashi, and Toshiyuki Shirai
    • Organizer
      AACR annual meeting
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2014-04-04 – 2014-04-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] 重粒子単独或はGemcitabine併用によるヒト膵癌幹細胞及び移植腫瘍抑制効果2013

    • Author(s)
      崔星、若井俊文、趙 建東、山田滋、鎌田正
    • Organizer
      第44回日本膵臓学会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] Defects in XRCC4 Alters Human Colon Cancer Stem Cell Markers and Enhances Its Radiosensitivity to X-ray and Carbon Ion Beam2013

    • Author(s)
      Sei Sai, Toshifumi Wakai, Guillaume Vares, Bing Wang, Mitsuru Nenoi, Tekehiko Kamijo, Toshiyuki Shirai, and Tadashi Kamada
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 重粒子線単独或はSorafenibやChk1阻害剤併用による肝癌幹細胞への影響2013

    • Author(s)
      崔星、若井俊文、白井敏之
    • Organizer
      第56回放射線影響学会
    • Place of Presentation
      青森
    • Related Report
      2013 Research-status Report
  • [Presentation] X線単独或はCisplatinやChk1阻害剤併用によるTriple Negative乳癌幹細胞への影響2013

    • Author(s)
      崔星、唐澤久美子、堀本義哉、Guillaume Vares、林光弘、白井敏之
    • Organizer
      第26回日本放射線腫瘍学会
    • Place of Presentation
      青森
    • Related Report
      2013 Research-status Report
  • [Presentation] Triple Negative乳癌幹細胞に対する重粒子とCisplatin、Chk1阻害剤併用による殺傷効果2013

    • Author(s)
      崔星、堀本義哉、林光弘、唐澤久美子
    • Organizer
      第10回日本乳癌学会・関東地方会
    • Place of Presentation
      大宮
    • Related Report
      2013 Research-status Report
  • [Presentation] Eradication of Gastrointestinal Cancer Stem Cells by Heavy Ion Radiotherapy2013

    • Author(s)
      Sei Sai and Toshiyuki Shirai
    • Organizer
      6th Annual World Congress of Regenerative Medicine & Stem Cells
    • Place of Presentation
      Dalian, China
    • Related Report
      2013 Research-status Report
  • [Presentation] Effects of Carbon Ion Beam Alone or in Combination with Chk1 Inhibitor and Gemcitabine on Putative Pancreatic Cancer Stem Cells2013

    • Author(s)
      Sei Sai, Toshiyuki Shirai, Tadashi Kamada
    • Organizer
      International Association of Pancreatology (IAP) and Korean Pancreatobiliary Association (KPBA)
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2013 Research-status Report
  • [Presentation] Effects of Carbon Ion Beam Alone or in Combination with Sorafenib on Putative Liver Cancer Stem Cells2013

    • Author(s)
      Sei Sai,Toshifumi Wakai, Jian-Dong Zhao, Toshiyuki Shirai, and Tadashi Kamada
    • Organizer
      The 17th ECCO, 38th ESMO, 32nd ESTRO European Cancer Congress
    • Place of Presentation
      Amsterdam, Netherlands
    • Related Report
      2013 Research-status Report
  • [Presentation] Carbon Ion Beams Are Effective in Targeting Cholangiocarcinoma Stem-Like Cells In Vitro and In Vivo2013

    • Author(s)
      Sei Sai, Toshifumi Wakai, Jian-Dong Zhao,Shigeru Yamada, Tadashi Kamada
    • Organizer
      Heavy Ion in Therapy and Space Radiation Symposium (HITSRS)
    • Place of Presentation
      Chiba, Japan
    • Related Report
      2013 Research-status Report
  • [Presentation] The Role of XRCC4 in Human Colon Cancer Stem Cell Properties and Radiosensitivity2013

    • Author(s)
      Sei Sai, Toshifumi Wakai, Guillaume Vares, Tadashi Kamada.
    • Organizer
      International Society for Stem Cell Research (ISSCR) 11 th Annual Meeting
    • Place of Presentation
      Boston, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Distinct Effects of Carbon Ion Beam and X-ray on Putative Liver Cancer Stem Cell In Vitro and In Vivo2013

    • Author(s)
      Sei Sai, Toshifumi Wakai, Tadashi Kamada
    • Organizer
      23rd Conference of the Asian Pacific Association for the Study of the Liver (APASL 2013)
    • Place of Presentation
      Singapore
    • Related Report
      2013 Research-status Report
  • [Presentation] がんの親玉―がん幹細胞を狙い撃ちできる重粒子治療 ――消化器系がんを中心に2013

    • Author(s)
      崔星
    • Organizer
      東海がんプロフェッショナル養成基盤推進プランセミナー
    • Place of Presentation
      名古屋
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] ヒト大腸癌細胞における癌幹細胞マーカー発現とXRCC4の役割2013

    • Author(s)
      崔星
    • Organizer
      第5回消化器疾患プロジェクト会議 2013年2月16日
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 重粒子線による癌幹細胞を標的とした癌治療の基礎的研究2013

    • Author(s)
      崔星
    • Organizer
      山梨大学医学部 (分子病理学講座) にて
    • Place of Presentation
      山梨県中央市
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 重粒子線による消化器癌幹細胞を標的とした癌治療の基礎的研究2013

    • Author(s)
      崔星
    • Organizer
      新潟大学医学部 (第一外科講座) にて
    • Place of Presentation
      新潟市
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 重粒子線によるヒト肝癌幹細胞生存率及びDNA損傷への影響2012

    • Author(s)
      崔星、山田滋、鎌田正
    • Organizer
      第25回日本放射線腫瘍学会・ 2012年11月23日~25日
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] Identification of Cholangiocarcinoma Stem-Like Cells and Its Radiosensitivity to Carbon Ion Beams2012

    • Author(s)
      Sei Sai, Toshifumi Wakai, Takehiko Kamijo,Shigeru Yamada, Tadashi Kamada
    • Organizer
      第71回日本癌学会学術総会 2012年9月19日~21日
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] 重粒子線による癌幹細胞を標的とした癌治療の基礎的研究2012

    • Author(s)
      崔星、上條岳彦、山田滋、鎌田正
    • Organizer
      日本放射線影響学会第55回大会2012年9月6日~8日
    • Place of Presentation
      仙台
    • Related Report
      2012 Research-status Report
  • [Presentation] 重粒子線照射によるヒト膵癌幹細胞生存率、DNA修復及び移植腫瘍への影響2012

    • Author(s)
      崔星、大西和彦、上條岳彦、山田滋、鎌田正.
    • Organizer
      第43回日本膵臓学会・2012年6月28日~29日 山形
    • Place of Presentation
      山形市
    • Related Report
      2012 Research-status Report
  • [Presentation] The Role of XRCC4 in Sensitizing Human Colon Cancer Stem-Like Cells to X-ray or Carbon Ion Beam2012

    • Author(s)
      Sei Sai, Kazuhiko Oonishi, Masahiko Mori, Takehiko Kamijo, Shigeru Yamada, and Tadashi Kamada.
    • Organizer
      ASTRO's 54th Annual Meeting October 28 - 31, 2012
    • Place of Presentation
      Boston, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Effects of Carbon Ion Beams on Liver Cancer Stem-Like Cells and Its Comparison with X-rays.2012

    • Author(s)
      Sei Sai, Kazuhiko Oonishi, Takehiko Kamijo, Shigeru Yamada, Tadashi Kamada
    • Organizer
      International Society for Stem Cell Research (ISSCR) 10 th Annual Meeting
    • Place of Presentation
      Yokohama, Japan
    • Related Report
      2012 Research-status Report
  • [Presentation] Effects of Carbon Ion Beam on Pancreatic Cancer Stem-Like Cells In Vitro and In Vivo2012

    • Author(s)
      Sei Sai, Kazuhiko Oonishi, Takehiko Kamijo, Shigeru Yamada, Tadashi Kamada
    • Organizer
      51st Annual Meeting of Particle Therapy Co-Operative Group (PTCOG51)
    • Place of Presentation
      Goyang, Seoul, Korea
    • Related Report
      2012 Research-status Report
  • [Presentation] Elimination of Cancer Stem Cells by Carbon Ion Beam ---A Promising New Strategy for Cancer Treatment2012

    • Author(s)
      崔星
    • Organizer
      韓国原子力研究院(KAERI)先端放射線技術研究所(ARTI)にて
    • Place of Presentation
      井邑市, 韓国
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Elimination of Cancer Stem Cells by Carbon Ion Beam ---A Promising New Strategy for Cancer Treatment2012

    • Author(s)
      崔星
    • Organizer
      中国延辺大学付属病院にて
    • Place of Presentation
      延吉市, 中国
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Eradication of Cancer Stem Cells by Heavy Ion Radiotherapy2012

    • Author(s)
      崔星
    • Organizer
      Columbia University Radiological Centerにて
    • Place of Presentation
      NewYork, USA
    • Related Report
      2012 Research-status Report
    • Invited

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi