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The investigation of new treatment for ovarian clear cell carcinoma with TOP2A amplification

Research Project

Project/Area Number 16H06907
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Obstetrics and gynecology
Research InstitutionKyoto University

Principal Investigator

Murakami Ryusuke  京都大学, 医学研究科, 特定病院助教 (40782363)

Project Period (FY) 2016-08-26 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords卵巣明細胞癌 / 染色体17番長腕増幅 / シスプラチン耐性 / PDK2 / 染色体17番長腕 / プラチナ抵抗性 / stemness / TP53 / TOP2A
Outline of Final Research Achievements

Ovarian clear cell carcinoma (CCC) has poor prognosis owing to its chemoresistance. Here we aimed to identify a biomarker of this drug resistance and the therapeutic target of CCC. Whole exome sequencing and expression microarray were conducted using 39 CCC clinical samples and 13 CCC cell lines. IC50 values and apoptosis of 13 CCC cell lines against cisplatin were measured by cleaved caspase-3. Chr17q21-24 amplification correlated positively with IC50 values for cisplatin in 13 CCC cell lines (r>0.4). The expression levels of 59 genes located on chr17q21-24 are positively correlated with Chr17q21-24 amplification in 13 CCC cell lines and 18 CCC patients (r>0.4). Of these 59 genes, we focused on pyruvate dehydrogenase kinase isoform 2(PDK2). A PDK inhibitor and suppression of PDK2 decreased the IC50 values for cisplatin by increasing cleaved caspase-3 expression. PDK2 inhibition is a promising therapeutic strategy against CCC.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • Research Products

    (3 results)

All 2017 2016

All Presentation (3 results) (of which Int'l Joint Research: 2 results)

  • [Presentation] Is the mesenchymal transition subtype more responsive to dose dense taxane chemotherapy combined with carboplatin (ddTC) than to conventional taxane and carboplatin chemotherapy (TC) in high grade serous ovarian carcinoma? A survey of Japanese Gynecology Oncology Group study (JGOG3016A1)2017

    • Author(s)
      Ryusuke Murakami, Noriomi Matsumura, Hiroshi Tanabe, Hirofumi Michimae, Mayu Yunokawa, Haruko Iwase, Motoi Sasagawa, Toshiaki Nakamura, Osamu Tokuyama, Masashi Takano, Toru Sugiyama, Takashi Sawasaki, Seiji Isonishi, Kazuhiro Takehara, Hidekatsu Nakai, Aikou Okamoto, Masaki Mandai, Ikuo Konishi
    • Organizer
      ASCO2017, J Clin Oncol 35, 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PDK2 contributes to the platinum resistance of ovarian clear cell carcinoma accompanied by chromosome 17q amplification2017

    • Author(s)
      Sachiko Kitamura, Ken Yamaguchi, Ryusuke Murakami, Kaoru Abiko Junzo Hamanishi, Tsukasa Baba, Noriomi Matsumura, Masaki Mandai
    • Organizer
      日本癌学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The investigation for overcoming platinum resistance of Ovarian Clear Cell Carcinoma with chromosome 17q amplification2016

    • Author(s)
      Sachiko Kitamura, Ken Yamaguchi, Ryusuke Murakami, Kaoru Abiko, Junzo Hamanishi, Tsukasa Baba, Noriomi Matsumura
    • Organizer
      がんプロ 5大学連携 香港合同教育セミンター
    • Place of Presentation
      プリンスオブウェールズ病院, Chinese University Hong Kong
    • Year and Date
      2016-10-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research

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Published: 2016-09-02   Modified: 2019-03-29  

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