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Drug screening for cholangiocarcinoma targeting the epigenetical mechanism of cancer progression

Research Project

Project/Area Number 15K10191
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKumamoto University

Principal Investigator

CHIKAMOTO Akira  熊本大学, 医学部附属病院, 准教授 (10419640)

Co-Investigator(Kenkyū-buntansha) 美馬 浩介  熊本大学, 医学部附属病院, 非常勤診療医師 (00546559)
中川 茂樹  熊本大学, 医学部附属病院, 医員 (10594872)
岡部 弘尚  熊本大学, 医学部附属病院, 助教 (40573621)
林 洋光  熊本大学, 医学部附属病院, 非常勤診療医師 (80625773)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords肝内胆管癌 / EZH2 / VASH1 / 血管新生 / 細胞増殖 / Notch1 / DZNep / 胆管癌 / 細胞周期 / アポトーシス / Angiogenesis
Outline of Final Research Achievements

Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) and regulate tumor malignancy by gene silencing via histone methylation. In this study, we investigate the role of EZH2 in angiogenesis of intrahepatic cholangiocarcinoma (ICC). The influence of EZH2 on tumor angiogenesis and the prognostic significance of EZH2 and VASH1 expression was also examined in ICC cohort by IHC.
By bioinformatical analysis, EZH2 was associated with several angiogenesis gene set in public database. We also find that EZH2 suppress VASH1 expression in vitro assay and IHC study. In IHC analysis. EZH2-high/VASH1-low status was independently associated with poor disease-free survival (P=0.019) and poor overall survival (P=0.0055). The current study demonstrated that high EZH2 expression was associated with activation of tumor angiogenesis, and the EZH2 mediated angiogenesis pathway predicts the prognosis of patients with ICC.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (11 results)

All 2018 2017 2016 2015 2013

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 2 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Prognostic impacts of postoperative complications in patients with intrahepatic cholangiocarcinoma after curative operations.2017

    • Author(s)
      Tatsunori Miyata, Yoichi Yamashita, Takanobu Yamao, Naoki Umezaki, Masayo Tsukamoto, Yuki Kitano, Kensuke Yamamura, Kota Arima, Takayoshi Kaida, Shigeki Nakagawa, Katsunori Imai, Daisuke Hashimoto, Akira Chikamoto, Takatoshi Ishiko, Hideo Baba.
    • Journal Title

      Int J Clin Oncol

      Volume: - Issue: 3 Pages: 526-532

    • DOI

      10.1007/s10147-017-1099-9

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Preoperative high SUVmax, associated with glucose transporter 1, predicts poor prognosis in pancreatic cancer.2017

    • Author(s)
      Chikamoto A, Inoue R, Komohara Y, Sakamaki K, Hashimoto D, Shiraishi S, Takamori H, Yamashita Y, Yoshida N, Yamanaka T, Yamashita Y, Baba H
    • Journal Title

      Ann Surg Oncol

      Volume: in press Issue: 7 Pages: 2040-2046

    • DOI

      10.1245/s10434-017-5799-1

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] C5a receptor (CD88) promotes motility and invasiveness of gastric cancer by activating RhoA.2016

    • Author(s)
      Kaida T, Nitta H, Kitano Y, Yamamura K, Arima K, Izumi D, Higashi T, Kurashige J, Imai K, Hayashi H, Iwatsuki M, Ishimoto T, Hashimoto D, Yamashita Y, Chikamoto A, Imanura T, Ishiko T, Beppu T, Baba H.
    • Journal Title

      Oncotarget.

      Volume: 20(7) Issue: 51 Pages: 84798-84809

    • DOI

      10.18632/oncotarget.12656

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Statin attenuates cell proliferative ability via TAZ (WWTR1) in hepatocellular carcinoma.2016

    • Author(s)
      Higashi T, Hayashi H, Kitano Y, Yamamura K, Kaida T, Arima K, Taki K, Nakagawa S, Okabe H, Nitta H, Imai K, Hashimoto D, Chikamoto A, Beppu T, Baba H.
    • Journal Title

      Med Oncol.

      Volume: 33(11) Issue: 11 Pages: 123-123

    • DOI

      10.1007/s12032-016-0845-6

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Heterogeneity of KRAS Mutations in Pancreatic Ductal Adenocarcinoma2016

    • Author(s)
      Hashimoto D, Arima K, Yokoyama N, Chikamoto A, Taki K, Inoue R, Kaida T, Higashi T, Nitta H, Ohmuraya M, Hirota M, Beppu T, Baba H
    • Journal Title

      Pancreas

      Volume: 45 Issue: 8 Pages: 1111-1114

    • DOI

      10.1097/mpa.0000000000000624

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An Imbalance in TAZ and YAP Expression in Hepatocellular Carcinoma Confers Cancer Stem Cell-like Behaviors Contributing to Disease Progression.2015

    • Author(s)
      Hayashi H, Higashi T, Yokoyama N, Kaida T, Sakamoto K, Fukushima Y, Ishimoto T, Kuroki H, Nitta H, Hashimoto D, Chikamoto A, Oki E, Beppu T, Baba H.
    • Journal Title

      Cancer Res.

      Volume: 75(22) Issue: 22 Pages: 4985-97

    • DOI

      10.1158/0008-5472.can-15-0291

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significance of P-cadherin overexpression and possible mechanism of its regulation in intrahepatic cholangiocarcinoma and pancreatic cancer.2015

    • Author(s)
      Sakamoto K, Imai K, Higashi T, Taki K, Nakagawa S, Okabe H, Nitta H, Hayashi H, Chikamoto A, Ishiko T, Beppu T, Baba H.
    • Journal Title

      Cancer Sci

      Volume: 106(9) Issue: 9 Pages: 1153-62

    • DOI

      10.1111/cas.12732

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Scoring system based on tumor markers and Child-Pugh classification for HCC patients who underwent liver resection.2015

    • Author(s)
      Nakagawa S, Hayashi H, Nitta H, Okabe H, Sakamoto K, Higashi T, Kuroki H, Imai K, Hashimoto D, Sakamoto Y, Chikamoto A, Beppu T, Baba H.
    • Journal Title

      Anticancer Res

      Volume: 35(4) Pages: 2157-63

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Enhancer of Zeste Homolog 2 (EZH2) Promotes Progression of Cholangiocarcinoma Cells by Regulating Cell Cycle and Apoptosis.2013

    • Author(s)
      Nakagawa S, Okabe H, Sakamoto Y, Hayashi H, Hashimoto D, Yokoyama N, Sakamoto K, Kuroki H, Mima K, Nitta H, Imai K, Chikamoto A, Watanabe M, Beppu T, Baba H.
    • Journal Title

      Ann Surg Oncol

      Volume: 3 Issue: S3 Pages: 667-675

    • DOI

      10.1245/s10434-013-3135-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] A stromal liver gene signature predictive of HCC risk across all liver disease etiologies2018

    • Author(s)
      Shigeki Nakagawa, Naoki Umesaki, Takanobu Yamao Yuki Kitano, Kensuke Yamamura, Kota Arima, Tatsunori Miyata, Takayoshi Kaida, Yujin Hoshida, Katsunori Imai,Daisuke Hashimoto, Yoichi Yamashita, Akira Chikamoto, Hideo Baba
    • Organizer
      AACR 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 肝細胞癌における多中心性及び肝内転移再発予測の為のMolecular gene signatureの検討2017

    • Author(s)
      中川茂樹、梅崎直紀、山尾宣暢、北野雄希、山村謙介、宮田辰徳、美馬浩介、今井克憲、橋本大輔、山下洋市、近本亮、馬場秀夫
    • Organizer
      第72回日本消化器外科学会総会
    • Related Report
      2017 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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