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Personalized medicine using newly identified paclitaxel-sensitive genes in gynecologic cancer

Research Project

Project/Area Number 21592146
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionTokyo Medical University

Principal Investigator

ISAKA Keiichi  東京医科大学, 医学部, 教授 (10201310)

Co-Investigator(Kenkyū-buntansha) NISHI Hirotaka  東京医科大学, 産科婦人科, 講師 (60307345)
Co-Investigator(Renkei-kenkyūsha) KURODA Masahiko  東京医科大学, 分子病理学, 教授 (80251304)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords癌 / 遺伝子 / 薬学 / 卵巣がん / 子宮体がん / パクリタキセル / 薬剤耐性 / テーラーメード医療
Research Abstract

Paclitaxel is often used in clinic to treat gynecologic cancers. Nevertheless, some carcinomas such as breast cancer, ovarian cancer, and non-small cell lung cancer demonstrate resistance to paclitaxel treatment. We screened a lentiviral siRNA library against the entire human genomes to assess the ability of clones to influence the sensitivity of paclitaxel. We identified three paclitaxel-resistant clones, which were determined as targeting for septin 10(SEPT10), ubiquitin-specific protease 15(USP15) and budding uninhibited by benzimidazoles 3(BUB3), respectively. We conducted the present study to investigate whether and how chemosensitivity can be determined by means of genetic diagnosis using these genes in patients with epithelial ovarian cancer. A total of 61 samples were obtained with informed consent from patients who had epithelial ovarian cancer and received first-line chemotherapy, consisting of paclitaxel and carboplatin(TC). The mRNA expression of SEPT10 and USP15 was measured by real-time reverse transcription-polymerase chain reaction. These expressions were showing a tendency to be higher in patients who did not respond to TC therapy. Also, SEPT10 expression was upregulated in serous type carcinoma compared with others. The present study suggests that genetic diagnosis by these genes may be useful to determine chemosensitivity in patients with epithelial ovarian cancer. Furthermore, these genes may candidate a novel cancer therapeutic method for paclitaxel-resistant cancers.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (5 results)

All 2012 2011 2009 Other

All Journal Article (2 results) (of which Peer Reviewed: 1 results) Presentation (3 results)

  • [Journal Article] Identification of a novel role of Septin 10 in Paclitaxel-resistance in cancers through a functional genomics screen2012

    • Author(s)
      Xu M, Takanashi M, Oikawa K, Nishi H, Isaka K, Yoshimoto T, Ohyashiki J, Kuroda M
    • Journal Title

      Cancer Sci

      Volume: 103 Issue: 4 Pages: 821-827

    • DOI

      10.1111/j.1349-7006.2012.02221.x

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] USP15 plays an essential role for caspase-3 activation during Paclitaxel-induced apoptosis2009

    • Author(s)
      Xu M, Takanashi M, Oikawa K, Tanaka M, Nishi H, Isaka K, Kudo M, Kuroda M.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 388 Pages: 366-371

    • URL

      http://www.sciencedirect.com/science/article/pii/S0006291X09015678

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Genetic diagnosis for chemosensitivity with paclitaxel-sensitive genes in epithelial ovarian cancer2011

    • Author(s)
      Hirotaka Nishi
    • Organizer
      16^<th> World Congress on Advances in Oncology
    • Place of Presentation
      Rhodes Island, Greece
    • Related Report
      2011 Annual Research Report
  • [Presentation] A functional genomic screen identifies a role of USP15 and Septin 10 in spindle-checkpoint and Paclitaxel-resistance in human cancers2009

    • Author(s)
      Mingli Xu, Masakatsu Takanashi, Kosuke Oikawa, Masami Tanaka, Hirotaka Nishi, Keiichi Isaka, Motoshige Kudo and Masahiko Kuroda
    • Organizer
      AACR Annual Meeting 2009
    • Place of Presentation
      Denver, CO, Abstrac
    • Related Report
      2011 Final Research Report
  • [Presentation] Genetic diagnosis for chemosensitivity with paclitaxel-sensitive genes in epithelial ovarian cancer

    • Author(s)
      Hirotaka Nishi, Toru Sasaki, Yotaro Takaesu, Yuzo Nagamitsu, Chinatsu Higuma, Fumitoshi Terauchi, Masahiko Kuroda, Keiichi Isaka
    • Organizer
      16th World Congress on Advances in Oncology
    • Place of Presentation
      Rhodes, Greece
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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