2013 Fiscal Year Final Research Report
Analysis of a mouse model of diffuse-type gastric cancer
| Project/Area Number |
24650609
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Carcinogenesis
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
YUASA Yasuhito 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (80111558)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| 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 |
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| 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.
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[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
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Journal Title
Oncogene
Volume: (in press)
DOI
Peer Reviewed
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[Journal Article] NF-κB inducing kinase, a central signaling component of the non-canonical pathway of NF-κB, contributes to ovarian cancer progression2014
Author(s)
Uno M, Saitoh Y, Mochida K, Tsuruyama E, Kiyono T, Imoto I, Inazawa J, Yuasa Y, Kubota T, Yamaoka S
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Journal Title
PLoS One
Volume: 9
Pages: e88347
DOI
Peer Reviewed
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[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
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Journal Title
PLoS One
Volume: 8
Pages: e72438
DOI
Peer Reviewed
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[Journal Article] Inhibition of histone demethylase JMJD1A improves anti-angiogenic therapy and reduces tumor associated macrophages2013
Author(s)
Osawa T, Tsuchida R, Muramatsu M, Shimamura T, Wang F, Suehiro J, Kanki Y, Wada Y, Yuasa Y, Aburatani H, Miyano S, Minami T, Kodama T, Shibuya M
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Journal Title
Cancer Res
Volume: 73
Pages: 3019-3028
DOI
Peer Reviewed
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[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
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Journal Title
Int. J. Cancer
Volume: 131
Pages: 2596-2603
Peer Reviewed
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