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

Analysis of a novel small-molecule compound inducing the degradation of a cisplatin resistance-related factor ERCC1

Research Project

Project/Area Number 25640089
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor therapeutics
Research InstitutionKanazawa University

Principal Investigator

MATSUNAGA Tsukasa  金沢大学, 薬学系, 教授 (60192340)

Co-Investigator(Kenkyū-buntansha) INOBE Manabu  金沢大学, 薬学系, 准教授 (10312414)
WAKASUGI Mitsuo  金沢大学, 薬学系, 助教 (80345595)
NISHINAGA Mari  富山県衛生研究所, 研究員 (10646681)
Co-Investigator(Renkei-kenkyūsha) KUNISHIMA Munetaka  金沢大学, 薬学系, 教授 (10214975)
ODA Akifumi  金沢大学, 薬学系, 准教授 (50433511)
ENDO Yoshio  金沢大学, がん進展制御研究所, 准教授 (30211783)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsヌクレオチド除去修復 / 阻害剤 / 抗癌剤 / シスプラチン / 低分子化合物 / 増感作用
Outline of Final Research Achievements

In this study, we have analyzed whether a small-molecule inhibitor of nucleotide excision repair (NERi) we recently found can potentiate the cytotoxic effects of cisplatin in cancer cells. The clonogenic survival assay revealed that NERi treatment increases the cisplatin-sensitivity of KKLS stomach cancer cell lines and A2780 ovarian cancer cell lines 2-3 fold. Using an immunoassay with damage-specific antibody, we showed that the removal of cisplatin-induced DNA intrastrand crosslinks is markedly attenuated by NERi treatment. Furthermore, in vivo experiments using murine Lewis lung carcinoma and C57BL/6 mice revealed that a combination of cisplatin and NERi significantly suppresses tumor growth, compared with cisplatin alone.

Report

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

    (13 results)

All 2015 2014 2013 Other

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

  • [Journal Article] Nucleotide excision repair-dependent DNA double-strand break formation and ATM signaling activation in mammalian quiescent cells2014

    • Author(s)
      Mitsuo Wakasugi, Takuma Sasaki, Megumi Matsumoto, Miyuki Nagaoka, Keiko Inoue, Manabu Inobe, Katsuyoshi Horibata, Kiyoji Tanaka, and Tsukasa Matsunaga
    • Journal Title

      J. Biological Chemistry

      Volume: 289 Issue: 41 Pages: 28730-28737

    • DOI

      10.1074/jbc.m114.589747

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rapid proliferation of activated lymph node CD4+ T Cells is achieved by eliminating gap phases in cell cycle progression.2014

    • Author(s)
      Mishima, T., Toda, S., Ando, Y., Matsunaga, T. and Inobe, M.
    • Journal Title

      Cell. Mol. Biol. Lett.

      Volume: 19 Issue: 4 Pages: 638-648

    • DOI

      10.2478/s11658-014-0219-z

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Concanavalin A-mediated T cell proliferation is regulated by Herpes Virus Entry Mediator costimulatory molecule.2014

    • Author(s)
      Ando, Y., Yasuoka, C., Mishima, T., Ikematsu, T., Uede, T., Matsunaga, T. and Inobe, M.
    • Journal Title

      In Vitro Cell. Dev. Biol.- Animal

      Volume: 50 Issue: 4 Pages: 313-320

    • DOI

      10.1007/s11626-013-9705-2

    • NAID

      120005349169

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proteasome inhibitors and knockdown of SMG1 cause accumulation of Upf1 and Upf2 in human cells.2014

    • Author(s)
      Zhao, X., Nogawa, A., Matsunaga, T., Takegami, T., Nakagawa, H. and Ishigaki, Y.
    • Journal Title

      Int. J. Oncol.

      Volume: 44 Issue: 1 Pages: 222-228

    • DOI

      10.3892/ijo.2013.2149

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The scaffold protein JLP plays a key role in regulating ultraviolet B-induced apoptosis in mice2014

    • Author(s)
      Enkhtuya R, Sato T, Wakasugi M, Tuvshintugs B, Miyata H, Sakurai T, Matsunaga T, Yoshioka K.
    • Journal Title

      Genes to Cells

      Volume: 19 Issue: 4 Pages: 350-358

    • DOI

      10.1111/gtc.12135

    • NAID

      120005440448

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] DNA修復因子ERCC1-XPFの安定性と細胞内局在性を決定する要因の解析2015

    • Author(s)
      高森千枝、宮崎幸太郎、西永真理、大澤琢郎、若杉光生、松永 司
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      兵庫医療大学(神戸)
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] NER-dependent DSB formation activates ATM signaling pathway in mammalian quiescent cells2015

    • Author(s)
      Wakasugi, M., Sasaki, T., Nagaoka, M., Matsumoto, M., Inoue, K., Horibata, K., Tanaka, K. and Matsunaga, T.
    • Organizer
      Keystone Symposia “Genomic instability and DNA repair joint with DNA replication and recombination”
    • Place of Presentation
      Whistler (Canada)
    • Year and Date
      2015-03-01 – 2015-03-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] 生体内の様々な細胞におけるヌクレオチド除去修復に依存した二次的DNA損傷の生成2014

    • Author(s)
      若杉光生、長岡美由紀、堀田侑希、松永 司
    • 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 Annual Research Report
  • [Presentation] シスプラチン抵抗性関連因子ERCC1を分解誘導する新規低分子化合物の同定2014

    • Author(s)
      松永 司、斎藤臣雄、長田裕之、遠藤良夫
    • Organizer
      第18回日本がん分子標的治療学会学術集会
    • Place of Presentation
      TKPガーデンシティ仙台(仙台)
    • Year and Date
      2014-06-25 – 2014-06-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 新開発セルベースドアッセイ系を利用したヌクレオチド除去修復研究の新展開2013

    • Author(s)
      松永 司
    • Organizer
      日本環境変異原学会第42回大会・シンポジウム「光遺伝毒性」
    • Place of Presentation
      岡山コンベンションセンター
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 癌細胞のシスプラチン感受性を増感させるヌクレオチド除去修復阻害剤の作用機序2013

    • Author(s)
      松永 司、西永真理、長田裕之、若杉光生
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] ヌクレオチド除去修復を阻害する低分子化合物の作用機序に関する解析2013

    • Author(s)
      西永真理、宮崎幸太郎、福島直紀、高森千枝、若杉光生、斎藤臣雄、長田裕之、松永 司
    • 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
    • Related Report
      2013 Research-status Report
  • [Remarks] 松永研究室|遺伝情報制御学

    • URL

      http://www.p.kanazawa-u.ac.jp/~iden/

    • Related Report
      2014 Annual Research Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi