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Study of prognostic biomarker KLF4 and Her4 for triple negative breast cancer

Research Project

Project/Area Number 25461975
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionUniversity of Toyama

Principal Investigator

Nagata Takuya  富山大学, 大学病院, 講師 (40303242)

Co-Investigator(Kenkyū-buntansha) TSUKADA Kazuhiro  富山大学, 大学院医学薬学研究部(医学), 教授 (90171967)
SHIMADA Yutaka  富山大学, 大学院医学薬学研究部(医学), 准教授 (30216072)
OZAWA Tatsuhiko  富山大学, 大学院医学薬学研究部(免疫学), 助教 (10432105)
吉田 徹  富山大学, 大学病院, 助教 (40456364)
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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsTNBC / CTC / KLF4 / siRNA / EMT / OS / DFS / 乳癌 / トリプルネガティブ / NANOG / 培養細胞株
Outline of Final Research Achievements

We assessed the expression levels of KLF4 in 84 patients with TNBC by immunohistochemical staining. In addition, CTCs in the peripheral blood of TNBC patients were identified and compared with primary lesions in terms of KLF4 expression. Moreover, the expression of KLF4 was inhibited by transfecting cultured TNBC cells with the siRNA of KLF4 to analyze the effects of KLF4 on cell proliferation and EMT-like changes.
In the 84 patients with TNBC, higher KLF4 expression was associated with significantly better OS and DFS. KLF4 expression was lower in CTCs than in cancer cells in TNBC primary lesions. TNBC cells with inhibited KLF4 expression exhibited a greater ability to growth. These cells also underwent EMT-like changes with reduced expression of epitherial factors such as E-cadherin.
TNBC patients with reduced KLF4 expression had poor outcomes. The results of our experiments suggest the expression of KLF4 is one of the important factors that inhibit the EMT and growth of TNBC.

Report

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

    (15 results)

All 2016 2015 2014 2013 2012 Other

All Journal Article (7 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Endoscopic thyroidectomy using the EZ-VANS method.2016

    • Author(s)
      Nagata T, Shimada Y, Miwa T, Hashimoto I, Kojima H, Okumura T, Tsukada K.
    • Journal Title

      Surg Today

      Volume: 46 Issue: 5 Pages: 575-582

    • DOI

      10.1007/s00595-015-1209-0

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Anticancer effect of a Kampo preparation Daikenchuto2016

    • Author(s)
      Nagata, T.; Toume, K.; Long, LX.; Hirano, K.; Watanabe, T.; Sekine, S.; Okumura, T.; Komatsu, K.; Tsukada, K.
    • Journal Title

      J. Nat. Med.

      Volume: 70 Issue: 3 Pages: 599-622

    • DOI

      10.1007/s11418-016-0989-x

    • NAID

      40020889440

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] p75 neurotrophin receptor expression is a characteristic of the mitotically quiescent cancer stem cell population present in esophageal squamous cell carcinoma.2016

    • Author(s)
      Yamaguchi T, Okumura T, Hirano K, Watanabe T, Nagata T, Shimada Y, Tsukada K.
    • Journal Title

      Int J Oncol

      Volume: 48 Issue: 5 Pages: 1943-1954

    • DOI

      10.3892/ijo.2016.3432

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Detection of circulating tumor cells by p75NTR expression in patients with esophageal cancer.2016

    • Author(s)
      Yamaguchi T, Okumura T*, Hirano K, Watanabe T, Nagata T, Shimada Y, Tsukada K
    • Journal Title

      World Journal of Surgical Oncology

      Volume: 14 Issue: 1 Pages: 40-47

    • DOI

      10.1186/s12957-016-0793-9

    • NAID

      120005758258

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 新規血液中浮遊癌細胞(CTC)捕捉システムによる乳癌患者末梢血液中のCTC同定と抗癌剤感受性予測2015

    • Author(s)
      長田拓哉, 大永 崇, 呂 暁龍, 渡辺 徹, 平野勝久, 奥村知之, 塚田一博
    • Journal Title

      癌と化学療法

      Volume: 42 Pages: 1240-1242

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 乳癌手術とドレーン管理2013

    • Author(s)
      長田拓哉、塚田一博
    • Journal Title

      プロフェッショナルがんナーシング

      Volume: 3 Pages: 11-14

    • Related Report
      2013 Research-status Report
  • [Journal Article] Prognostic significance of NANOG and KLF4 in breast carcinoma patients2012

    • Author(s)
      Nagata T, Shimada Y, Sekine S, Osawa S, Hori R, Matsui K, Okumura T, Fukuoka J, Tsukada K
    • Journal Title

      Breast Cancer 2012

      Volume: 21 Issue: 1 Pages: 96-101

    • DOI

      10.1007/s12282-012-0357-y

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Analysis of circulating tumor cell (CTC) from breast cancer patients with new CTC-chip2015

    • Author(s)
      Nagata T, Tsukada K.
    • Organizer
      46th World Congress of Surgery
    • Place of Presentation
      Bangkok Thailand
    • Year and Date
      2015-08-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 新規解析装置を用いた血液中浮遊乳癌細胞(CTC)の同定2015

    • Author(s)
      長田拓哉, 松井恒志, 橋本伊佐也, 塚田一博.
    • Organizer
      第23回日本乳癌学会総会
    • Place of Presentation
      東京
    • Year and Date
      2015-07-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] トリプルネガティブ乳癌におけるKLF4を介した転移調節機構2015

    • Author(s)
      長田拓哉, 塚田一博
    • Organizer
      第36回癌免疫外科研究会
    • Place of Presentation
      鹿児島
    • Year and Date
      2015-05-14
    • Related Report
      2015 Annual Research Report
  • [Presentation] トリプルネガティブ乳癌の治療選択におけるNanog, KLF4発現解析の有用性2015

    • Author(s)
      長田拓哉, 松井恒志, 吉岡伊作, 関根慎一, 橋本伊佐也, 渋谷和人, 森山亮仁, 北條荘三, 奥村知之, 塚田一博
    • Organizer
      第115回日本外科学会定期学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-04-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] トリプルネガティブ乳癌(TNBC)の予後予測マーカー・KLF4に関する多施設共同研究2014

    • Author(s)
      長田拓哉
    • Organizer
      日本乳癌学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-07-12 – 2014-07-14
    • Related Report
      2014 Research-status Report
  • [Presentation] iPS細胞誘導因子KLF4は乳癌TN症例のバイオマーカーとして有用である

    • Author(s)
      長田拓哉、松井恒志、北條荘三、渡辺智子、堀 亮太、吉岡伊作、澤田成朗、奥村知之、吉田 徹、嶋田 裕、福岡順也、塚田一博
    • Organizer
      第113回日本外科学会定期学術集会
    • Place of Presentation
      福岡
    • Related Report
      2013 Research-status Report
  • [Presentation] トリプルネガティブ乳癌におけるバイオマーカー・KLF4の有用性

    • Author(s)
      長田拓哉、松井恒志、橋本伊佐也、神山公希、塚田一博
    • Organizer
      第21回日本乳癌学会学術総会
    • Place of Presentation
      浜松
    • Related Report
      2013 Research-status Report
  • [Presentation] iPS誘導因子KLF4が持つトリプルネガティブ乳癌における予後予測因子としての意義

    • Author(s)
      長田拓哉、東山考一、清水哲郎、島多勝夫、田澤賢一、松井公志、吉岡伊作、橋本伊佐也、渋谷和人、神山公希 、奥村知之、澤田成朗、吉田徹、塚田一博
    • Organizer
      第114回日本外科学会定期学術集会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report

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

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