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Novel molecular targeting strategy against chromosomal maintenance factor FANCJ

Research Project

Project/Area Number 25460390
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionKyushu University

Principal Investigator

KITAO HIROYUKI  九州大学, 医学(系)研究科(研究院), 准教授 (30368617)

Co-Investigator(Kenkyū-buntansha) IIMORI Makoto  九州大学, 医学研究院, 助教 (20546460)
MORITA Masaru  独立行政法人国立病院機構(九州がんセンター), その他部局等, 消化器外科部長 (30294937)
OKI Eiji  九州大学, 大学病院, 講師 (70380392)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords染色体不安定性 / 抗がん剤 / FANCJ / FdUrd / トリフルリジン / ロンサーフ(TFTD,TAS-102) / 抗癌剤
Outline of Final Research Achievements

Chromosomal stability is ensured by the accurate DNA replication and the equal segregation of duplicated chromosomes. In tumors, such mechanism is often disrupted and chromosomal instability, which is represented as high mutation frequency and abnormal number of chromosomes, emerges. In our previous study, we reported that the colorectal cancer patients who exhibited higher expression of chromosomal stability factor FANCJ in their tumors tended to be poor prognosis and less effective with 5-FU-based chemotherapy (Nakanishi et al. Ann Surg Oncol 2012). In this project, we drugged the underlying molecular mechanism of the association between FANCJ expression and 5-FU resistance experimentally and found that the physical interaction between FANCJ and key partners are critical.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (18 results)

All 2015 2014 2013 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (5 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Trifluridine Induces p53-Dependent Sustained G2 Phase Arrest with Its Massive Misincorporation into DNA and Few DNA Strand Breaks2015

    • Author(s)
      Matsuoka K, Iimori M, Niimi S, Tsukihara H, Watanabe S, Kiyonari S, Kiniwa M, Ando K, Tokunaga E, Saeki H, Oki E, Maehara Y, Kitao H.
    • Journal Title

      Molecular Cancer Therapeutics

      Volume: 14 Issue: 4 Pages: 1004-1013

    • DOI

      10.1158/1535-7163.mct-14-0236

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The 1,2-diaminocyclohexane carrier ligand in oxaliplatin induces p53-dependent transcriptional repression of factors involved in thymidylate biosynthesis.2015

    • Author(s)
      Kiyonari S, Iimori M, Matsuoka K, Watanabe S, Morikawa-Ichinose T, Miura D, Niimi S, Saeki H, Tokunaga E, Oki E, Morita M, Kadomatsu K, Maehara Y, Kitao H
    • Journal Title

      Mol Cancer Ther

      Volume: 14 Issue: 10 Pages: 2332-42

    • DOI

      10.1158/1535-7163.mct-14-0748

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chromosomal instability associated with global DNA hypomethylation is associated with the initiation and progression of esophageal squamous cell carcinoma2014

    • Author(s)
      Kawano H, Saeki H, Kitao H, Tsuda Y, Otsu H, Ando K, Ito S, Egashira A, Oki E, Morita M, Oda Y, Maehara Y.
    • Journal Title

      Annals of Surgical Oncology

      Volume: 4 Issue: S4 Pages: 696-702

    • DOI

      10.1245/s10434-014-3818-z

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oxidative DNA damage in human esophageal cancer: clinicopathological analysis of 8-hydroxydeoxyguanosine and its repair enzyme.2014

    • Author(s)
      Kubo N, Morita M, Nakashima Y, Kitao H, Egashira A, Saeki H, Oki E, Kakeji Y, Oda Y, Maehara Y.
    • Journal Title

      Dis Esophagus.

      Volume: 27 Issue: 3 Pages: 285-293

    • DOI

      10.1111/dote.12107

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rad9, Rad17, TopBP1 and claspin play essential roles in heat-induced activation of ATR kinase and heat tolerance2013

    • Author(s)
      Tuul M
    • Journal Title

      PLoS One

      Volume: 8巻(2号) Issue: 2 Pages: 55361-55361

    • DOI

      10.1371/journal.pone.0055361

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of ribonucleotide reductase-M1 in 5-fluorouracil induced DNA damage in esophageal cancer cell lines.2013

    • Author(s)
      Aoki Y, Sakogawa K, Hihara J, Emi M, Hamai Y, Kono K, Shi L, Sun J, Kitao H, Ikura T, Niida H, Nakanishi M, Okada M, Tashiro S.
    • Journal Title

      Int J Oncol.

      Volume: 42(6) Issue: 6 Pages: 1951-60

    • DOI

      10.3892/ijo.2013.1899

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] The 1,2-diaminocyclohexane carrier ligand in oxaliplatin induces p53-dependent transcriptional repression of factors involved in thymidylate biosynthesis2015

    • Author(s)
      北尾洋之
    • Organizer
      27th AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics
    • Place of Presentation
      Hynes Convention Center, Boston, MA, USA
    • Year and Date
      2015-11-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cellular response to a fluorinated thymidine analogue trifluridine, a key component of the novel oral antitumor drug TAS-102.2015

    • Author(s)
      Hiroyuki Kitao
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      Rockport, RI
    • Year and Date
      2015-06-28 – 2015-07-03
    • Related Report
      2014 Research-status Report
  • [Presentation] Cellular response to a fluorinated thymidine analogue trifluridine, a key component of the novel oral antitumor drug TAS-1022015

    • Author(s)
      北尾洋之
    • Organizer
      Gordon Research Conference on Nucleosides, Nucleotides and Oligonucleotides
    • Place of Presentation
      Salva Regina University, Newport, RI, USA
    • Year and Date
      2015-06-28
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Trifluridine induces p53-dependent sustained G2 phase arrest with its massive misincorporation into DNA and few DNA strand breaks2015

    • Author(s)
      Kazuaki Matsuoka, Hiroyuki Kitao
    • Organizer
      American Association of Cancer Research (AACR) Annual Meeting 2015
    • Place of Presentation
      Philadelphia, PA
    • Year and Date
      2015-04-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 新規経口ヌクレオシド型抗腫瘍薬「ロンサーフ」の作用機序2015

    • Author(s)
      北尾 洋之
    • Organizer
      九州大学先端融合医療レドックスナビ研究拠点若手研究者主催シンポジウム
    • Place of Presentation
      福岡
    • Year and Date
      2015-01-27
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Trifluorothymidine induces p53-dependent sustained G2 arrest without extensive DNA strand-breaks2013

    • Author(s)
      Kazuaki Matsuoka, Makoto Iimori, Hiroshi Tsukihara, Shinichi Kiyonari, Sugiko Watanabe, Eiji Oki, Hiroyuki Kitao, Yoshihiko Maehara
    • Organizer
      第36回日本分子生物学会総会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Remarks] 九州大学消化器・総合外科(第二外科)

    • URL

      http://www.kyudai2geka.com

    • Related Report
      2015 Annual Research Report
  • [Remarks] 九州大学大学院 消化器・総合外科(第二外科)

    • URL

      http://www.kyudai2geka.com/

    • Related Report
      2014 Research-status Report
  • [Remarks] 九州大学先端融合医療レドックスナビ研究拠点 先端がん診断・創薬グループ

    • URL

      http://redoxnavi.kyushu-u.ac.jp/group4/

    • Related Report
      2014 Research-status Report
  • [Remarks] 九州大学大学院 消化器・総合外科(第二外科)

    • URL

      http://www.kyudai2geka.com/

    • Related Report
      2013 Research-status Report
  • [Remarks] 九州大学先端融合医療レドックスナビ研究拠点 先端がん診断・創薬グループ

    • URL

      http://redoxnavi.kyushu-u.ac.jp/group4/

    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] 検出剤、該検出剤を含むキット、被験試料中のDNAに取り込まれたトリフルリジンを検出する方法およびトリフルリジンまたはトリフルリジンを含む抗悪性腫瘍剤の抗腫瘍効果を判定する方法2015

    • Inventor(s)
      北尾洋之、諸富洋介、木庭守、前原喜彦
    • Industrial Property Rights Holder
      北尾洋之、諸富洋介、木庭守、前原喜彦
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-10-08
    • Related Report
      2015 Annual Research Report

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

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