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Molecular targeted drug discovery for cancer cell radiosensitization using RNA technology

Research Project

Project/Area Number 23390301
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionTottori University

Principal Investigator

KURIMASA Akihiro  鳥取大学, 医学(系)研究科(研究院), 准教授 (80343276)

Co-Investigator(Kenkyū-buntansha) OKAYASU Ryuichi  放射線医学総合研究所, 放射線防護センターリスク低減化研究プログラム, 主任研究員 (50356135)
Project Period (FY) 2011-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2014: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2013: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2011: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Keywordsがん / 放射線 / 放射線生物影響 / RNA工学 / 画像工学 / DNA修復 / 分子標的創薬 / DNA損傷 / RNA / アプタマー / RNA
Outline of Final Research Achievements

RNA aptamers are artificial synthetic ribonucleic acids that form a higher-order structure and bind phosphorylated sites of specific protein. We will develop novel cancer therapy by utilizing RNA aptamers for controlling radio-sensitivities of malignant cells during radiation therapy for cancer. We tried making RNA aptamers against phosphorylated sites of DNA-PKcs by SELEX, and produced specific molecules to DNA-PK. Some of the RNA enhanced sensitivity of radiation for U2OS cells. In this experiment, we also try to construct an expression system of RNA aptamers using lenti-virus RNA expression vector, and try to find a good candidate molecule for therapy. Furthermore, for developing better radiation therapy, we combine RNA technology and live cell-imaging technology for evaluating DNA damage and cell cycle progression.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (20 results)

All 2015 2014 2013 2012 2011

All Journal Article (10 results) (of which Peer Reviewed: 9 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) Book (1 results)

  • [Journal Article] The combination of Hsp90 inhibitor 17AAG and heavy-ion irradiation provides effective tumor control in human lung cancer cells.2015

    • Author(s)
      Hirokazu Hirakawa, Hiroshi Fujisawa, Aya Masaoka, Miho Noguchi, Ryoichi Hirayama, Momoko Takahashi, Akira Fujimori, Ryuichi Okayasu
    • Journal Title

      Cancer Medicine

      Volume: 4 Issue: 3 Pages: 426-436

    • DOI

      10.1002/cam4.377

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Differential Radiosensitivity Phenotypes of DNA-PKcs Mutations Affecting NHEJ and HRR Systems following Irradiation with Gamma-Rays or Very Low Fluences of Alpha Particles.2014

    • Author(s)
      Lin YF, Nagasawa H, Little JB, Kato TA, Shih HY, Xie XJ, Wilson PF Jr, Brogan JR, Kurimasa A, Chen DJ, Bedford JS, Chen BP.
    • Journal Title

      PLoS One.

      Volume: 9(4) Issue: 4 Pages: e93579-e93579

    • DOI

      10.1371/journal.pone.0093579

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential Radiosensitivity Phenotypes of DNA-PKcs Mutations Affecting NHEJ and HRR Systems following Irradiation with Gamma-Rays or Very Low Fluences of Alpha Particles.2014

    • Author(s)
      Lin YF, Nagasawa H, Little JB, Kato TA, Shih HY, Xie XJ, Wilson PF Jr, Brogan JR, Kurimasa A, Chen DJ, Bedford JS, Chen BP
    • Journal Title

      PLoS One.

      Volume: 9(4)

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Parg deficiency confers radio-sensitization through enhanced cell death in mouse ES cells exposed to various forms of ionizing radiation.2013

    • Author(s)
      Shirai H, Fujimori H, Gunji A, Maeda D, Hirai T, Poetsch AR, Harada H, Yoshida T, Sasai K, Okayasu R, Masutani M.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 435(1) Pages: 100-6

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selective enhancing effect of early mitotic inhibitor 1 (Emi1) depletion on the sensitivity of doxorubicin or X-ray treatment in human cancer cells.2013

    • Author(s)
      Shimizu N, Nakajima NI, Tsunematsu T, Ogawa I, Kawai H, Hirayama R, Fujimori A, Yamada A, Okayasu R, Ishimaru N, Takata T, Kudo Y.
    • Journal Title

      J Biol Chem.

      Volume: 288(24) Pages: 17238-52

    • NAID

      120006718350

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Visualisation of γH2AX foci caused by heavy ion particle traversal; distinction between core track versus non-track damage.2013

    • Author(s)
      Nakajima NI, Brunton H, Watanabe R, Shrikhande A, Hirayama R, Matsufuji N, Fujimori A, Murakami T, Okayasu R, Jeggo P, Shibata A.
    • Journal Title

      PLoS One.

      Volume: 8(8)

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The complexity of DNA double strand breaks is a critical factor enhancing end-resection.2013

    • Author(s)
      Yajima H1, Fujisawa H, Nakajima NI, Hirakawa H, Jeggo PA, Okayasu R, Fujimori A.
    • Journal Title

      DNA Repair (Amst).

      Volume: 12(11) Pages: 936-46

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exo1 plays a major role in DNA end resection in humans and influences double-strand break repair and damage signaling decisions.2012

    • Author(s)
      Tomimatsu N, Mukherjee B, Deland K, Kurimasa A, Bolderson E, Khanna KK, Burma S
    • Journal Title

      DNA Repair (Amst)

      Volume: 11(4) Issue: 4 Pages: 441-8

    • DOI

      10.1016/j.dnarep.2012.01.006

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Differential role of DNA-PKcs phosphorylations and kinase activity in radiosensitivity and chromosomal instability.2011

    • Author(s)
      Nagasawa H, Little JB, Lin YF, So S, Kurimasa A, Peng Y, Brogan JR, Chen DJ, Bedford JS and Chen BP
    • Journal Title

      Radiat Res

      Volume: 175(1) Issue: 1 Pages: 83-89

    • DOI

      10.1667/rr2092.1

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NK314 potentiates anti-tumor activity with adult T-cell leukemia-lymphoma cellsby inhibition of dual targets on topoisomerase II{alpha}c and DNA-dependent protein kinase.2011

    • Author(s)
      Hisatomi T, Sueoka-Aragane N, Sato A, Tomimasu R, Ide M, Kurimasa A, Okamoto K, Kimura S and Sueoka E
    • Journal Title

      Blood

      Volume: 117(13) Issue: 13 Pages: 3575-84

    • DOI

      10.1182/blood-2010-02-270439

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] The spatiotemporal dynamics of centrosomes and the genome during first cleavage in human tripronuclear zygotes in vitro.2015

    • Author(s)
      Kai Y., Kurimasa A., Iwata K., Yumoto K., Iba Y., Mio Y.
    • Organizer
      Europian Society of Human Reproduction and Embryology Annual Meeting 2015
    • Place of Presentation
      Portugal, Lisbon
    • Year and Date
      2015-06-14 – 2015-06-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] Live cell imaging of DNA double-strand breaks (DSBs) foci and evaluation of cell cycle perturbation induced by Topoisomerase inhibitors2015

    • Author(s)
      Kurimasa A.
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      京都府京都市(国立京都国際会館)
    • Year and Date
      2015-05-25 – 2015-05-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] 移動・変化する細胞核の追尾と細胞核内スポットの計測を自動で行う画像処理システムの開発2014

    • Author(s)
      廣江翼、河野清尊、栗政晃弘
    • Organizer
      第23回計測自動制御学会中国支部学術講演会
    • Place of Presentation
      福山大学 福山 広島
    • Year and Date
      2014-12-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] DNA2本鎖切断損傷ライブセルイメージングによる損傷フォーカス形成と細胞周期の乱れの評価2013

    • Author(s)
      栗政明弘
    • Organizer
      日本放射線影響学会 第56回大会 ワークショップW10「DNA損傷のセンシングと分子細胞応答の最前線」
    • Place of Presentation
      青森、クラウンパレス青森
    • Related Report
      2013 Annual Research Report
  • [Presentation] DNA2本鎖切断損傷ライブセルイメージングによるトポイソメラーゼ阻害剤の薬効評価2012

    • Author(s)
      堀田絵理香、宮野佳子、岡田茜、矢倉はるな、末岡榮三朗、栗政明弘
    • Organizer
      日本放射線影響学会、第55回大会
    • Place of Presentation
      仙台(東北大学)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Live cell imaging of DNA double-strand breaks (DSBs) foci induced by topoisomerase inhibitors and evaluation of cell cycle progression.2012

    • Author(s)
      Hotta E, Miyano Y, Okada A, Yakura H, Sueoka E, Iwabuchi K, Kurimasa A
    • Organizer
      28th RBC-NIRS International Symposium
    • Place of Presentation
      Kyoto, Co-op Inn Kyoto
    • Related Report
      2012 Annual Research Report
  • [Presentation] Live cell imaging and kinetics of DNA double-strand breaks (DSBs) foci in cycling U2OS cells.2012

    • Author(s)
      Hotta E, Okada A, Miyano Y, Tomimatsu N, Iwabuchi K, Chen DJ, Kurimasa A
    • Organizer
      The 14th International Workshop on Ataxia-Telangiectasia (ATW2012)
    • Place of Presentation
      Radisson Blu Hotel, Paschim Vihar, New Delhi, INDIA
    • Related Report
      2011 Annual Research Report
  • [Presentation] U2OS細胞におけるDNA2本鎖切断損傷フォーカスのライブセルイメージングとその動態2011

    • Author(s)
      栗政明弘、堀田絵理香、富松望、岩淵邦芳、David J. Chen
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋(コンベンションセンター)
    • Related Report
      2011 Annual Research Report
  • [Presentation] U2OS細胞におけるDNA2本鎖切断損傷フォーカスのライブセルイメージングとその動態2011

    • Author(s)
      堀田絵理香、岡田茜、宮野佳子、富松望、岩淵邦芳、David J. Chen、栗政明弘
    • Organizer
      日本放射線影響学会、第54回大会
    • Place of Presentation
      神戸(商工会議所会館)
    • Related Report
      2011 Annual Research Report
  • [Book] 細胞周期とDNA損傷を検出するバイオセンサーとその画像解析システム バイオセンサの迅速・簡易・高機能化技術と課題解説書 第8章 第10節:医療用バイオセンサ開発における課題と解決策の取り組み事例 がん化学療法剤スクリーニングのためのバイオセンサーシステムの開発事例2014

    • Author(s)
      栗政明弘
    • Total Pages
      13
    • Publisher
      技術情報協会
    • Related Report
      2014 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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