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Development of a novel therapeutic strategy utilizing PARP inhibitors in combination with radiotherapy based on cancer-specific abnormalities in homologous recombination

Research Project

Project/Area Number 23591836
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Radiation science
Research InstitutionThe University of Tokyo

Principal Investigator

HOSOYA Noriko  東京大学, 医学(系)研究科(研究院), 講師 (00396748)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords癌 / 相同組換え / 放射線 / PARP阻害剤 / DNA損傷応答
Research Abstract

SYCP3 is one of the components of the synaptonemal complex, the structure essential for meiotic recombination. The protein is not expressed in normal mitotic cells, but is aberrantly expressed in various cancers. Since we have found that SYCP3 inhibits homologous recombination by interfering with BRCA2 in mitotic cells, in this study, we examined whether the mitotic cells expressing SYCP3 is sensitive to the PARP inhibitor or combination therapies of the PARP inhibitor and agents that exert anti-tumor activities by inducing DNA double-strand breaks. Cells expressing SYCP3 showed extreme hypersensitivity to the PARP inhibitor NU1025, and pretreatment with radiation or cisplatin markedly enhanced this hypersensitivity. These findings would serve as a molecular basis for developing novel therapies for SYCP3-expressing tumors.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (33 results)

All 2014 2013 2012 2011 Other

All Journal Article (7 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (26 results) (of which Invited: 3 results)

  • [Journal Article] Targeting DNA damage response in cancer therapy.2014

    • Author(s)
      Hosoya N, Miyagawa K
    • Journal Title

      Cancer Sci.

      Volume: 105 Issue: 4 Pages: 370-388

    • DOI

      10.1111/cas.12366

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-tumor activity of olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, in cultured endometrial carcinoma cells2014

    • Author(s)
      A. Miyasaka, K. Oda, Y. Ikeda, O. Wada-Hiraike, T. Kashiyama, A. Enomoto, N. Hosoya, T. Koso, T. Fukuda, K. Inaaba, K. Sone, Y. Uehara, R. Kurikawa, K. Nagasaka, Y.Matsumoto, T. Arimoto, S. Nakagawa, H. Kuramoto, K. Miyagawa, T. Yano, K. Kawana, Y. Osuga, T. Fujii.
    • Journal Title

      BMC Cancer

      Volume: 14 Issue: 1 Pages: 179-179

    • DOI

      10.1186/1471-2407-14-179

    • URL

      https://pure.teikyo.jp/en/publications/f996ce24-f9b5-4341-813a-49220ade8663

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The DNA damage responses: important determinants of the biological responses to radiation.2013

    • Author(s)
      Hosoya N, Miyagawa K
    • Journal Title

      J Phys Conf Ser

      Volume: 印刷中

    • NAID

      120005650267

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 放射線の晩発影響2012

    • Author(s)
      細谷紀子
    • Journal Title

      BIO MEDICA

      Volume: 27(5) Pages: 39-44

    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Journal Article] Synaptonemal complex protein SYCP3 impairs mitotic recombination by interfering with BRCA22012

    • Author(s)
      Hosoya N
    • Journal Title

      EMBO Rep

      Volume: 13 Issue: 1 Pages: 44-51

    • DOI

      10.1038/embor.2011.221

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synaptonemal complex protein SYCP3 impairs mitotic recombination by interfering with BRCA2.2012

    • Author(s)
      Hosoya N, Okajima M, Kinomura A, Fujii Y, Hiyama T, Sun J, Tashiro S, Miyagawa K.
    • Journal Title

      EMBO reports

      Volume: 13 Pages: 44-51

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] がんにおけるゲノム不安定性2011

    • Author(s)
      細谷紀子
    • Journal Title

      細胞

      Volume: 43(6) Pages: 13-16

    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] がん精巣抗原SYCE1の体細胞発現によるDNA損傷抵抗性の誘導2013

    • Author(s)
      細谷紀子, 藤井義大、宮川清
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸国際展示場(兵庫県神戸市)
    • Year and Date
      2013-12-03
    • Related Report
      2013 Final Research Report
  • [Presentation] 減数分裂特異的分子SMC1betaは、体細胞において、コヒーシンと干渉し、DNAの二重鎖切断の修復を阻害する2013

    • Author(s)
      後藤悌、細谷紀子、宮川清
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2013-10-05
    • Related Report
      2013 Final Research Report
  • [Presentation] The cancer-testis antigen SYCE2 impairs chromosome stability by activating ATM2013

    • Author(s)
      Hosoya N, Miyagawa K
    • Organizer
      Chromatin, Replication and Chromosomal Stability 2013
    • Place of Presentation
      BRIC, University of Copenhagen, Copenhagen, Denmark
    • Year and Date
      2013-06-18
    • Related Report
      2013 Final Research Report
  • [Presentation] がん精巣抗原SYCE1の体細胞発現によるDNA損傷抵抗性の誘導2013

    • Author(s)
      細谷紀子, 藤井義大、宮川清
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド・神戸国際会議場・神戸国際展示場・神戸ポートピアホテル(兵庫県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 減数分裂特異的分子SMC1betaは、体細胞において、コヒーシンと干渉し、DNAの二重鎖切断の修復を阻害する2013

    • Author(s)
      後藤悌、細谷紀子、宮川清
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] The meiosis-specific synaptonemal complex proteins modulate the intrinsic homologous recombination pathway in human cancer cells2012

    • Author(s)
      細谷紀子, 宮川清
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡(福岡県福岡市)
    • Year and Date
      2012-12-11
    • Related Report
      2013 Final Research Report
  • [Presentation] The synaptonemal complex protein SYCE2 activates ATM and induces chromosome instability in tumors2012

    • Author(s)
      Hosoya N, Miyagawa K
    • Organizer
      第74回日本血液学会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2012-10-20
    • Related Report
      2013 Final Research Report
  • [Presentation] がん精巣抗原によるゲノム不安定性の誘導と治療応用2012

    • Author(s)
      細谷紀子
    • Organizer
      日本女性科学者の会第9回学術大会
    • Place of Presentation
      アルカディア市ヶ谷(東京都新宿区)
    • Year and Date
      2012-10-08
    • Related Report
      2013 Final Research Report
  • [Presentation] The role for a meiosis-specific protein in regulating DNA damage response and chromosome stability in cancer2012

    • Author(s)
      Hosoya N, Miyagawa K
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市教育文化会館(北海道札幌志)
    • Year and Date
      2012-09-19
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒトがん細胞における異所性発現分子によるDNA損傷応答の多様な制御機構2012

    • Author(s)
      細谷紀子
    • Organizer
      日本放射線影響学会第55回大会
    • Place of Presentation
      東北大学川内北キャンパス(宮城県仙台市)
    • Year and Date
      2012-09-07
    • Related Report
      2013 Final Research Report
  • [Presentation] がんにおける減数分裂特異的分子の異所性発現の生物学的役割の解明2012

    • Author(s)
      細谷紀子、宮川清
    • Organizer
      第49回日本臨床分子医学会学術集会
    • Place of Presentation
      みやこめっせ(京都府京都市)
    • Year and Date
      2012-04-14
    • Related Report
      2013 Final Research Report
  • [Presentation] 減数分裂特異的分子SYCP3の体細胞発現の生物学的役割2012

    • Author(s)
      細谷紀子、宮川清
    • Organizer
      第119回小児血液腫瘍懇話会
    • Place of Presentation
      東京医科歯科大学(東京都文京区)
    • Year and Date
      2012-02-17
    • Related Report
      2013 Final Research Report
  • [Presentation] 減数分裂特異的分子SYCP3の体細胞発現の生物学的役割2012

    • Author(s)
      細谷紀子
    • Organizer
      第119回小児血液腫瘍懇話会(招待講演)
    • Place of Presentation
      東京医科歯科大学(東京都)
    • Related Report
      2011 Research-status Report
  • [Presentation] 減数分裂特異的分子の体細胞発現による中心体異常の誘導2011

    • Author(s)
      細谷紀子
    • Organizer
      第3回中心体研究会
    • Place of Presentation
      東京理科大学森戸記念館(東京都新宿区)
    • Year and Date
      2011-12-17
    • Related Report
      2013 Final Research Report
  • [Presentation] The synaptonemal complex protein SYCE2 induces chromosome instability in mitotic cells through activation of the ataxia-telangiectasia-mutated kinase2011

    • Author(s)
      細谷紀子, 宮川清
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2011-12-16
    • Related Report
      2013 Final Research Report
  • [Presentation] Expression of the meiosis-specific cohesion SMC1beta interferes with mitotic cohesion2011

    • Author(s)
      Goto Y, Hosoya N, Miyagawa K
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2011-10-04
    • Related Report
      2013 Final Research Report
  • [Presentation] The synaptonemal complex protein SYCE2 induces chromosome instability through activation of ATM in cancer2011

    • Author(s)
      Hosoya N, Miyagawa K
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2011-10-04
    • Related Report
      2013 Final Research Report
  • [Presentation] The synaptonemal complex protein SYCE2 induces chromosome instability through activation of ATM in cancer2011

    • Author(s)
      Noriko Hosoya
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Related Report
      2011 Research-status Report
  • [Presentation] The synaptonemal complex protein SYCE2 induces chromosome instability in mitotic cells through activation of the ataxia-telangiectasia-mutated kinase2011

    • Author(s)
      Noriko Hosoya
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2011 Research-status Report
  • [Presentation] 減数分裂特異的分子の体細胞発現による中心体異常の誘導2011

    • Author(s)
      細谷紀子
    • Organizer
      第3回中心体研究会(招待講演)
    • Place of Presentation
      東京理科大学 森戸記念館(東京都)
    • Related Report
      2011 Research-status Report
  • [Presentation] The meiosis-specific synaptonemal complex proteins modulate the intrinsic homologous recombination pathway in human cancer cells

    • Author(s)
      細谷紀子, 宮川清
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡(福岡県)
    • Related Report
      2012 Research-status Report
  • [Presentation] The synaptonemal complex protein SYCE2 activates ATM and induces chromosome instability in tumors

    • Author(s)
      細谷紀子, 宮川清
    • Organizer
      第74回日本血液学会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Related Report
      2012 Research-status Report
  • [Presentation] がん精巣抗原によるゲノム不安定性の誘導と治療応用

    • Author(s)
      細谷紀子
    • Organizer
      日本女性科学者の会第9回学術大会
    • Place of Presentation
      アルカディア市ヶ谷(東京都)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] The role for a meiosis-specific protein in regulating DNA damage response and chromosome stability in cancer

    • Author(s)
      Noriko Hosoya
    • Organizer
      第71回日本癌学会学術総会 Symposia 1 「Recent development of chromosome and genome instability research」
    • Place of Presentation
      札幌市教育文化会館(北海道)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] ヒトがん細胞における異所性発現分子によるDNA損傷応答の多様な制御機構

    • Author(s)
      細谷紀子
    • Organizer
      日本放射線影響学会第55回大会
    • Place of Presentation
      東北大学川内北キャンパス(宮城県)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] がんにおける減数分裂特異的分子の異所性発現の生物学的役割の解明

    • Author(s)
      細谷紀子、宮川清
    • Organizer
      第49回日本臨床分子医学会学術集会
    • Place of Presentation
      みやこめっせ(京都府)
    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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