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Development of the loco-systemic cancer therapy combining localized radiation and novel immune adjuvant mesoporous silica

Research Project

Project/Area Number 26670548
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Radiation science
Research InstitutionUniversity of Tsukuba

Principal Investigator

Tsuboi Koji  筑波大学, 医学医療系, 教授 (90188615)

Co-Investigator(Kenkyū-buntansha) ZENKOH Junko  筑波大学, 医学医療系, 研究員 (20710148)
ITO Atsuo  国立研究開発法人産業技術総合研究所, 生命工学領域 健康工学研究部門 生体材料研究グループ, 研究グループ長 (30356480)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords放射線治療生物学 / 免疫応答細胞死
Outline of Final Research Achievements

Localized radiotherapy for cancers has an effect of immune adjuvant by inducing immunogenic cell death. The signals from dying or newly dead cells evoke anti-tumor immunity that is mediated by activated CTLs.
In this study, murine glioma cells GL261 were inoculated to syngeneic albino C57BL/6 mice. Mesoporous silica nanoparticles (MSNs) were used as an immune adjuvant. Intra-tumoral injection of MSNs was combined with localized X-ray irradiation, and the tumor growth rates and survival were analyzed. In addition, the immune-enhancing effect of indomethacin was examined.
Consequently, MSNs administration (0.1 mg/mouse) once a week for 3 weeks delayed tumor growth significantly. Moreover, 6 times administrations induced complete cure in 90% of the treated mice inducing abscopal effect in the brain. Furthermore, sequential oral administration of indomethacin enhanced anti-tumor effect and prolonged survivals of the mice. MSNs may be a promising candidate for a novel immune adjuvant.

Report

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

    (15 results)

All 2015 2014

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Invited: 2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Generation of low-flux X-ray micro-planar beams and their biological effect on a murine subcutaneous tumor model.2015

    • Author(s)
      Hong Z, Zenkoh J, Le B, Gerelchuluun A, Suzuki K, Moritake T, Washio M, Urakawa J, Tsuboi K.
    • Journal Title

      J Radiat Res.

      Volume: 56 Issue: 5 Pages: 768-776

    • DOI

      10.1093/jrr/rrv037

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Major DNA Repair Pathway after Both Proton and Carbon-Ion Radiation is NHEJ, but the HR Pathway is More Relevant in Carbon Ions.2015

    • Author(s)
      Gerelchuluun A, Manabe E, Ishikawa T, Sun L, Itoh K, Sakae T, Suzuki K, Hirayama R, Asaithamby A, Chen DJ, Tsuboi K.
    • Journal Title

      Radiat Res.

      Volume: 183 Issue: 3 Pages: 345-356

    • DOI

      10.1667/rr13904.1

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Long-term survival after treatment of glioblastoma multiforme with hyperfractionated concomitant boost proton beam therapy.2015

    • Author(s)
      Mizumoto M, Yamamoto T, Takano S, Ishikawa E, Matsumura A, Ishikawa H, Okumura T, Sakurai H, Miyatake S, Tsuboi K.
    • Journal Title

      Pract Radiat Oncol.

      Volume: 5 Issue: 1 Pages: e9-e16

    • DOI

      10.1016/j.prro.2014.03.012

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] X線とセレコキシブの併用は癌細胞に強い小胞体ストレスを負荷してcalreticulinの発現を上昇させる2015

    • Author(s)
      鈴木健之、ゲレルチュルン・アリウンゲレル、真鍋絵梨、善光純子、坪井康次
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場、愛知
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 放射線照射により誘導される免疫細胞死は脳内へもアブスコパル効果をもたらす2015

    • Author(s)
      善光 純子、鈴木 健之、ゲレルチュルン・アリウンゲレル、大野 忠夫、坪井 康次
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場、愛知
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] HDAC阻害剤であるSAHAの陽子線増感効果についての研究2015

    • Author(s)
      真鍋絵梨、ゲレルチュルン・アリウンゲレル、鈴木健之、善光純子、加藤宝光、David Chen J、榮武二、坪井康次
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場、愛知
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 陽子線とHDAC阻害剤の併用治療法に関する基礎的研究2015

    • Author(s)
      ゲレルチュルン・アリウンゲレル、真鍋絵梨、志村友梨、鈴木健之、善光純子、坪井康次
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場、愛知
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] The Combination of X-rays and Celecoxib Causes The Strong ER Stress to Tumor Cells and Raises Expression of Calreticulin.2015

    • Author(s)
      Kenshi Suzuki, Ariungerel Gerelchuluun, Lue Sun, Takaaki Ishikawa, Kazuya Ito, Eri Manabe, Junko Zenkoh, Koji Tsuboi
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      京都国際会館、京都
    • Year and Date
      2015-06-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] Radiation Induced Tumor Cell Death Bring about the "Abscopal Effect" in the Brain2015

    • Author(s)
      Junko Zenkoh, Ariungerel Gerelchuluun, Kenshi Suzuki, Xiupeng Wang, Atsuo Ito, Tadao Ohno, Koji Tsuboi
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      京都国際会館、京都
    • Year and Date
      2015-06-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] DNA Repair Pathways for DNA Damages Induced By Proton and Carbon-ion Beams.2015

    • Author(s)
      Ariungerel Gerelchuluun, Eri Manabe, Takaaki Ishikawa, Takeji Sakae, Kenshi Suzuki, Ryoichi Hirayama, Aroumougame Asaithambi, David J Chen, Koji Tsuboi
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      京都国際会館、京都
    • Year and Date
      2015-06-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] A HDAC Inhibitor, Suberoylanilide Hydroxamic Acid Enhances Biological Effect of Proton Beams.2015

    • Author(s)
      Eri Manabe, Ariungerel Gerelchuluun, Kenshi Suzuki, Takeji Sakae, Takamitsu Kato, David J Chen, Koji Tsuboi
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      京都国際会館、京都
    • Year and Date
      2015-06-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] 放射線による細胞死研究の新展開 細胞死につながる初期過程を考察する2014

    • Author(s)
      坪井康次、鈴木健之、Gerelchuluun Ariungerel
    • 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)
    • Year and Date
      2014-10-01 – 2014-10-03
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Biological effectiveness of clinically used proton beam2014

    • Author(s)
      Ariungerel Gerelchuluun 、石川隆昭、真鍋絵梨、孫略、伊東和也、鈴木健之、善光純子、Aroumougame Asaithambi, David J Chen、坪井康次
    • 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)
    • Year and Date
      2014-10-01 – 2014-10-03
    • Related Report
      2014 Research-status Report
  • [Presentation] 放射線神経生物学の夜明け 多形性膠芽腫に対する陽子線治療2014

    • Author(s)
      坪井康次
    • Organizer
      第57回日本神経化学会大会
    • Place of Presentation
      奈良県文化会館(奈良)
    • Year and Date
      2014-09-29 – 2014-10-01
    • Related Report
      2014 Research-status Report
    • Invited
  • [Patent(Industrial Property Rights)] メソポーラスシリカ粒子2015

    • Inventor(s)
      王秀鵬,十河友,伊藤敦夫,大野忠夫,坪井康次,善光純子
    • Industrial Property Rights Holder
      産業技術総合研究所、セルメディシン(株)
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-171512
    • Filing Date
      2015-08-31
    • Related Report
      2015 Annual Research Report

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Published: 2014-04-04   Modified: 2017-05-10  

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