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Molecular targeted drug discovery for cancer cell radiosensitization using RNA aptamars

Research Project

Project/Area Number 20200039
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)

Allocation TypeSingle-year Grants
Research Field Radiation science
Living organism molecular science
Research InstitutionTottori University

Principal Investigator

KURIMASA Akihiro  Tottori University, 大学院・医学系研究科, 准教授 (80343276)

Co-Investigator(Kenkyū-buntansha) NIWA Ohtaura  放射線医学総合研究所, 重粒子医科学センター, 副センター長 (80093293)
OKAYASU Ryuichi  放射線医学総合研究所, 重粒子医科学センター, グループリーダー (50356135)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥31,590,000 (Direct Cost: ¥24,300,000、Indirect Cost: ¥7,290,000)
Fiscal Year 2010: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2009: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Fiscal Year 2008: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
Keywords放射線治療生物学 / 分子標的創薬 / DNA修復 / RNA工学 / 生理活性物質 / RNAアプタマー / タンパク質リン酸化 / 癌治療
Research Abstract

It is well known that blocking protein kinases related to DNA repair machinery such as DNA-PKcs, ATM, or ATR enhance sensitivity to ionizing radiation (IR). From this point of view, we expect that tumor cell sensitivity against radiotherapy is enhanced by exploiting this mechanism. Protein kinases related to DNA repair machinery are activated by being phosphorylated. Therefore we attempted making the RNA engineering technology, and will develop new radiation sensitization medicine as a molecular target drug for cancer. In this experiment, we are making RNA aptamers against phosphorylated site of DNA-PKcs by SELEX. In this research, we produced RNA aptamers specific to DNA-PKcs phosphorylation site. Furtheremore their specific template sequences were analyzed by next-generation sequencing technology, and some that may recognize DNA-PKcs specifically were focused. U2OS cells are transfected with the RNA molecules, we tested whether can increase sensitivity of radiation. In conclusion, we found some RNA molecules that enhance sensitivity of radiation for U2OS cells.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (23 results)

All 2011 2010 2009 Other

All Journal Article (10 results) (of which Peer Reviewed: 5 results) Presentation (12 results) Remarks (1 results)

  • [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, Sueoka E
    • Journal Title

      Blood 117(13)

      Pages: 3575-84

    • Related Report
      2010 Final 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, Chen BP
    • Journal Title

      Radiat Res 175

      Pages: 83-9

    • Related Report
      2010 Final Research Report
  • [Journal Article] Differential role of DNA-PKcs phosphorylations and kinase activity in radiosensitivity and chromosomal instability.2011

    • Author(s)
      Nagasawa H
    • Journal Title

      Radiat Res

      Volume: 175 Pages: 83-89

    • Related Report
      2010 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} and DNA-dependent protein kinase.2011

    • Author(s)
      Hisatomi T
    • Journal Title

      Blood

      Volume: 117(13) Pages: 3575-3584

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of N-acetyltransferase human in the cytotoxic activity of 5-fluorouracil.2009

    • Author(s)
      Takubo K, Tsuchiya H, Kurimasa A, Arnesen T, Ryoke K, Shiota G.
    • Journal Title

      Anticaneer Drugs 20(8)

      Pages: 668-75

    • Related Report
      2010 Final Research Report
  • [Journal Article] SIRT2 down- regulation confers resistance to microtubule inhibitors by prolonging chronic mitotic arrest.2009

    • Author(s)
      Inoue T, Nakayama Y, Yamada H, Li YC, Yamaguchi S, Osaki M, Kurimasa A, Hiratsuka M, Katoh M, Oshimura M.
    • Journal Title

      Cell Cyele 8(8)

      Pages: 1279-91

    • Related Report
      2010 Final Research Report
  • [Journal Article] SIRT2 downregulation confers resistance to microtubule inhibitors by prolonging chronic mitotic arrest.2009

    • Author(s)
      Inoue T
    • Journal Title

      Cell Cycle 15:8(8)

      Pages: 1279-1291

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of N-acetyltransferase human in the cytotoxic activity of 5-fluorouracil.2009

    • Author(s)
      Takubo K
    • Journal Title

      Anticancer Drugs. 20(8)

      Pages: 668-675

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effectiveness of combined treatment using X-rays and a phosphoinositide 3-kinase inhibitor, ZSTK474, on proliferation of HeLa cells in vitro and in vivo.

    • Author(s)
      Anzai K, Sekine-Suzuki E, Ueno M, Okamura M, Yoshimi H, Dan S, Yaguchi SI, Enami J, Yamori T, Okayasu R
    • Journal Title

      Caneer Sei. in press

    • NAID

      10029294463

    • Related Report
      2010 Final Research Report
  • [Journal Article] Effectiveness of combined treatment using X-rays and a phosphoinositide 3-kinase inhibitor, ZSTK474, on proliferation of HeLa cells in vitro and in vivo.

    • Author(s)
      Anzai K
    • Journal Title

      Cancer Sci.

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Live Cell Imaging and kinetics of DNA double-strand breaks (DBSs)foci in cycling U2OS cells.2011

    • Author(s)
      Kurimasa A, Okuda S, Okada A, Tomimatsu N, Iwabuchi K, Chen DJ.
    • Organizer
      Genomic Instability and DNA repair in Keystone symposia on Molecular and Cellular Biology
    • Place of Presentation
      Keystone, Colorado, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] DNA resection by Exol dictates critical DNA repair and damage signaling decisions in response to DNA double-strand breaks.2011

    • Author(s)
      Tomimatsu N, Mukherjee B, Deland K, Kurimasa A, Porteus M, Bolderson E, Khanna KK, Burma S.
    • Organizer
      Genomic Instability and DNA repair in Keystone symposia on Molecular and Cellular Biology
    • Place of Presentation
      Keystone, Colorado, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] Live Cell Imaging and kinetics of DNA double-strand breaks (DBSs) foci in cycling U2OS cells.2011

    • Author(s)
      Kurimasa A
    • Organizer
      Genomic Instability and DNA repair" in Keystone symposia on Molecular and Cellular Biology
    • Place of Presentation
      Keystone, Colorado, USA
    • Related Report
      2010 Annual Research Report
  • [Presentation] DNA resection by Exo1 dictates critical DNA repair and damage signaling decisions in response to DNA double-strand breaks.2011

    • Author(s)
      Tomimatsu N
    • Organizer
      Genomic Instability and DNA repair" in Keystone symposia on Molecular and Cellular Biology
    • Place of Presentation
      Keystone, Colorado, USA
    • Related Report
      2010 Annual Research Report
  • [Presentation] Laser and ionizing radiation induced DSB fbci fbrmation : in vivo real time imaging using modified 53BP1-GFP fusion protein.2010

    • Author(s)
      Kurimasa A, Nagayoshi Y, Okuda S, Okada A, Tomimatsu N, Iwabuchi K, Chen DJ.
    • Organizer
      Recent Advances in DNA Repair and Related Studies 6th NIRS International Open Laboratory Workshop
    • Place of Presentation
      放射線医学総合研究所、千葉
    • Year and Date
      2010-03-24
    • Related Report
      2010 Final Research Report
  • [Presentation] Laser and ionizing radiation induced DSB foci formation : in vivo real time imaging using modified 53BP1-GFP fusion protein.2010

    • Author(s)
      Kurimasa A
    • Organizer
      "Recent Advances in DNA Repair and Related Studies" 6th NIRS International Open Laboratory Workshop
    • Place of Presentation
      放射線医学総合研究所、千葉
    • Year and Date
      2010-03-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] DNA二本鎖切断再結合におけるATMと53BP1の役割2010

    • Author(s)
      井原誠、小林純也、栗政明弘、小松賢志、工藤崇
    • Organizer
      日本放射線影響学会、第53回大会
    • Place of Presentation
      京都テルサ、京都
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Analysis of novel phosphorylation site of 53BPI induced by DNA double-strand breaks.2010

    • Author(s)
      Kurimasa A, Nagayoshi Y, Okuda S, Okada A, Tomimatsu N, Iwabuchi K, Chen DJ.
    • Organizer
      A-T International Workshop 2010
    • Place of Presentation
      Redondo Beach, California, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] Analysis of novel phosphorylation site of 53BP1 induced by DNA double-strand breaks.2010

    • Author(s)
      Kurimasa A
    • Organizer
      A-T International Workshop 2010
    • Place of Presentation
      Crown Plaza Hotel, Redondo Beach, California
    • Related Report
      2009 Annual Research Report
  • [Presentation] がん放射線治療の展開と生物影響の基礎研究2009

    • Author(s)
      丹羽太貫
    • Organizer
      茨城大学理学部量子サイエンスフォーラム 公開シンポジウム第2回Quantum Medicine研究会
    • Place of Presentation
      茨城大学理学部(水戸市文京2-1-1)
    • Year and Date
      2009-01-31
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] DNA-PKリン酸化部位に対するRNAアプタマーの作製2009

    • Author(s)
      奥田沙奈絵、永吉悠里、岡田茜、押村光雄、汐田剛史、栗政明弘
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] DNA2本鎖切断により誘導される53BP1新規リン酸化部位の解析2009

    • Author(s)
      永吉悠里、奥田沙奈絵、岡田茜、押村光雄、汐田剛史、栗政明弘
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2018-03-28  

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