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Analysis of a mouse model of diffuse-type gastric cancer

Research Project

Project/Area Number 24650609
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Carcinogenesis
Research InstitutionTokyo Medical and Dental University

Principal Investigator

YUASA Yasuhito  東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (80111558)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords胃がん / マウスモデル / 治療薬 / E-カドヘリン / p53 / エピジェネティクス / 遺伝子改変動物 / 抗がん剤 / がん幹細胞
Research Abstract

We have reported an E-cadherin/p53 double conditional knockout (DCKO) mouse line as the first genetically engineered diffuse-type gastric cancer (DGC), which recapitulates human DGC morphologically and molecularly. Recently, we have also established mouse DGC (MDGC) cell lines from primary tumors and lymph node metastases of the DCKO mice. We observed that the expression levels of epigenetic modulators and frequently methylated genes were up- and down-regulated in mouse primary DGC, respectively. Treatment with some epigenetic inhibitors induced differentiation and attenuated sphere formation of the MDGC cell lines in vitro. Moreover, we could validate tumor-suppressing activity of these agents in vivo. These results suggest that epigenetic alterations may play significant roles in diffuse-type gastric carcinogenesis and support to develop a relevant therapeutic strategy in human DGC.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (30 results)

All 2014 2013 2012 Other

All Journal Article (14 results) (of which Peer Reviewed: 13 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (15 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] BMP4/Thrombospondin-1 loop paracrinically inhibits tumor angiogenesis and suppresses the growth of solid tumors2014

    • Author(s)
      Tsuchida R, Osawa T, Wang F, Nishii R, Das B, Tsuchida S, Muramatsu M, Takahashi T, Inoue T, Wada Y, Minami T, Yuasa Y, Shibuya M
    • Journal Title

      Oncogene

      Volume: 33 Issue: 29 Pages: 3803-3811

    • DOI

      10.1038/onc.2013.358

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] NF-κB Inducing Kinase, a Central Signaling Component of the Non-Canonical Pathway of NF-κB, Contributes to Ovarian Cancer Progression.2014

    • Author(s)
      Uno M, Saitoh Y, Mochida K, Tsuruyama E, Kiyono T, Imoto I, Inazawa J, Yuasa Y, Kubota T, Yamaoka S.
    • Journal Title

      PLoS One

      Volume: 9(2) Issue: 2 Pages: e88347-e88347

    • DOI

      10.1371/journal.pone.0088347

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Circulating microRNAs as biomarkers for early detection of diffuse-type gastric cancer using a mouse model2013

    • Author(s)
      Rotkrua P, Shimada S, Mogushi, K, Akiyama Y, Tanaka H, Yuasa Y
    • Journal Title

      Brit. J. Cancer

      Volume: 108 Issue: 4 Pages: 932-940

    • DOI

      10.1038/bjc.2013.30

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] CD49f^<high> cells retain sphere-forming and tumor-initiating activities in human gastric tumors2013

    • Author(s)
      Fukamachi H, Seol HS, Shimada S, Funasaka C, Baba K, Kim JH, Park YS, Kawachi H, Yook JH, Eishi Y, Kojima K, Kim WH, Jang SJ, Yuasa Y
    • Journal Title

      PLoS One

      Volume: 8 Issue: 8 Pages: e72438-e72438

    • DOI

      10.1371/journal.pone.0072438

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Multiple-to-multiple relationships between microRNAs and target genes in gastric cancel2013

    • Author(s)
      Hashimoto Y, et al.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 5 Pages: e62589-e62589

    • DOI

      10.1371/journal.pone.0062589

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of histone demethylase JMJD1A improves anti-angiogenic therapy and reduces tumor associated macrophages2013

    • Author(s)
      Shimamura T, Wang F, Suehiro J, Kanki Y, Wada Y, Yuasa Y, Aburatani H, Miyano S, Minami T, Kodama T, Shibuya M
    • Journal Title

      Cancer Res

      Volume: 73 Issue: 10 Pages: 3019-3028

    • DOI

      10.1158/0008-5472.can-12-3231

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activin A regulates growth of gastro-intestinal epithelial cells by mediating epithelial-mesenchymal interaction2013

    • Author(s)
      Fukamachi H, Kato S, Asashima M, Ichinose M, Yuasa Y
    • Journal Title

      Development Growth and Differentiation

      Volume: 55 Issue: 9 Pages: 786

    • DOI

      10.1111/dgd.12102

    • NAID

      40019937971

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Insulin-like growth factor 2 hypomethylation of blood leukocyte DNA is associated with gastric cancer risk2012

    • Author(s)
      Yuasa Y, Nagasaki H, Oze I, Akiyama Y, Yoshida S, Shitara K, Ito S, Hosono S, Watanabe M, Ito H, Tanaka H, Kang DH, Pan K-F, You W-C, Matsuo K
    • Journal Title

      Int. J. Cancer

      Volume: 131 Pages: 2596-2603

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synergistic tumour suppressor activity of E-cadherin and p53 in a conditional mouse model for metastatic diffuse-type gastric cancer2012

    • Author(s)
      Shimada S, Mimata A, Sekine M, Mogushi K, Akiyama Y, Fukamachi H, Jonkers J, Tanaka H, Eishi Y, Yuasa Y
    • Journal Title

      Gut

      Volume: 61 Pages: 344-353

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of serum microRNAs as novel non-invasive biomarkers for early detection of gastric cancer2012

    • Author(s)
      Song M-Y, Pan K-F, Su H-J, Zhang L, Ma J-L, Li J-Y, Yuasa Y, KangDH, Kim YS, You W-C
    • Journal Title

      PLoS One

      Volume: 7

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] IGF2 hypomethylation of blood leukocyte DNA is associated with gastric cancer risk2012

    • Author(s)
      Yuasa Y, et al.
    • Journal Title

      Int.J.Cancer

      Volume: (in press) Issue: 11 Pages: 2596-2603

    • DOI

      10.1002/ijc.27554

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of serum microRNAs as novel non-invasive biomarkers for early detection of gastric cancer2012

    • Author(s)
      Song M-Y, et al.
    • Journal Title

      PLoS One

      Volume: 7 Issue: 3 Pages: e33608-e33608

    • DOI

      10.1371/journal.pone.0033608

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] DNA Methylation in Peripheral Blood: A Potential Biomarker for Cancer Molecular Epidemiology2012

    • Author(s)
      Li L, Choi JY, Lee KM, Sung H, Park SK, Oze I, Pan KF, You WC, Chen YX, Fang JY, Matsuo K, Kim WH, Yuasa Y, Kang D.
    • Journal Title

      Journal of Epidemiology

      Volume: 22 Issue: 5 Pages: 384-394

    • DOI

      10.2188/jea.JE20120003

    • NAID

      130001913612

    • ISSN
      0917-5040, 1349-9092
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] スキルス胃癌マウスモデル研究の展望2012

    • Author(s)
      島田周、秋山好光、湯浅保仁
    • Journal Title

      日本臨床

      Volume: 70 Pages: 1660-1665

    • Related Report
      2012 Research-status Report
  • [Presentation] Targeting epigenetic alterations in a mouse model of E-cadherin/p53-deficient diffuse-type gastric cancer2013

    • Author(s)
      Shimada S, Akiyama Y, Fukamachi H, Yuasa Y
    • Organizer
      NRF A3 Foresight Program 2013 Seminar - Epigenetic Signatures in Gastric Carcinogenesis
    • Place of Presentation
      扶余,韓国
    • Related Report
      2013 Final Research Report
  • [Presentation] Alterations of histone lysine methyltransferases, SETDB1 and SETDB2, in gastric cancers2013

    • Author(s)
      Nishikawaji T, Akiyama Y, Shimada S, Yuasa Y
    • Organizer
      NRF A3 Foresight Program 2013 Seminar - Epigenetic Signatures in Gastric Carcinogenesis
    • Place of Presentation
      扶余,韓国
    • Related Report
      2013 Final Research Report
  • [Presentation] Frequent loss of SET7/9 protein and its clinicopathological significance in gastric carcinoma2013

    • Author(s)
      Akiyama Y, Koda Y, Nishikawaji T, Shimada S, Yuasa Y
    • Organizer
      第72回日本癌学会総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Function and expression of Twist1 in diffuse-type gastric cancer cell lines of an E-cadherin/p53-deficient mouse model2013

    • Author(s)
      Sakamoto A, Shimada S, Akiyama Y, Yuasa Y
    • Organizer
      第72回日本癌学会総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Patient-dependent differences in the features of human gastric tumor-initiating cells in primary culture2013

    • Author(s)
      Fukamachi H, Shimada S, Yuasa Y
    • Organizer
      第72回日本癌学会総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Targeting epigenetic alterations in a mouse model of E-cadherin/p53-deficient diffuse-type gastric cancer2013

    • Author(s)
      Shimada S, Akiyama Y, Fukamachi H, Yuasa Y
    • Organizer
      NRF A3 Foresight Program 2013 Seminar
    • Place of Presentation
      韓国プヨ
    • Related Report
      2013 Annual Research Report
  • [Presentation] Alterations of histone lysine methyltransferases, SETDB1 and SETDB2, in gastric cancers2013

    • Author(s)
      Nishikawaji T, Akiyama Y, Shimada S, Yuasa Y
    • Organizer
      NRF A3 Foresight Program 2013 Seminar
    • Place of Presentation
      韓国プヨ
    • Related Report
      2013 Annual Research Report
  • [Presentation] Summary of GC stem cell researches in the A3 project2013

    • Author(s)
      Fukamachi H, Seol HS, Shimada S, Kim WH, Jang SJ, Yuasa Y
    • Organizer
      NSFC A3 Foresight Program 2013 Seminar
    • Place of Presentation
      中国桂林
    • Related Report
      2013 Annual Research Report
  • [Presentation] 胃がんにおけるヒストン修飾関連遺伝子SET7の異常とその機能解析.2012

    • Author(s)
      秋山好光、甲田裕樹、橋本裕、湯浅保仁.
    • Organizer
      第6回日本エピジェネティクス研究会年会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] Functional analysis of Twist1 in diffuse-type gastric cancer cell lines of an E-cadherin/p53-deficient mouse model.2012

    • Author(s)
      Sakamoto A, Shimada S, Akiyama Y, Yuasa Y.
    • Organizer
      NRF A3 Foresight Program 2012 Seminar Epigenetic Signatures in Gastric Carcinogenesis
    • Place of Presentation
      Busan, Korea
    • Related Report
      2012 Research-status Report
  • [Presentation] Loss of SET7, a histone H3K4 methyltransferase, and its function in gastric cancer.2012

    • Author(s)
      Akiyama Y, Koda Y, Nishikawaji T, Shimada S, Yuasa Y.
    • Organizer
      第71回日本癌学会総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] Human gastric tumor-initiating cells form spheres in culture, and are more resistant to anti-cancer agents.2012

    • Author(s)
      Fukamachi H, Shimada S, Yuasa Y.
    • Organizer
      第71回日本がん学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] Identification of circulating miRNA as biomarkers for early detection of diffuse-type gastric cancer using a mouse model.2012

    • Author(s)
      Shimada S, Rotkrua P, Akiyama Y, Yuasa Y.
    • Organizer
      第71回日本がん学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] Loss of SET7, a histone H3K4 methyltransferase, in gastric cancer.2012

    • Author(s)
      Akiyama Y, Koda Y, Nishikawaji T, Shimada S, Zhu WG, Yuasa Y.
    • Organizer
      The Third International Cancer Epigenetics Meeting
    • Place of Presentation
      Beijing, China
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Over-expression of SETDB2, a histone methyltransferase, in gastric cancers.2012

    • Author(s)
      Nishikawaji T, Akiyama Y, Shimada S, Yuasa Y.
    • Organizer
      NSFC A3 Foresight Program 2012 Seminar Epigenetic Signatures in Gastric Carcinogenesis
    • Place of Presentation
      Hangzhou, China
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.tmd.ac.jp/grad/monc/index.html

    • Related Report
      2013 Final Research Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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