2013 Fiscal Year Annual Research Report
大腸上皮の癌化に伴う管腔形成異常メカニズムの解明
Publicly Offered Research
| Project Area | Regulation of polarity signaling during morphogenesis, remodeling, and breakdown of epithelial tubular structure |
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| Project/Area Number |
24112523
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| Research Institution | Keio University |
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Principal Investigator |
佐藤 俊朗 慶應義塾大学, 医学部, 特任准教授 (70365245)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | 三次元培養 / 大腸がん / 幹細胞 |
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| Research Abstract |
我々は，ヒト臨床検体を用い，腸管上皮幹細胞ならびに大腸がん上皮細胞の3次元培養法（オルガノイド培養）を開発した. 本研究計画では樹立した大腸がんオルガノイドを用いて，上皮細胞の管腔構造形成の異常メカニズムの解明を目的としている．平成24年度は大腸がん症例数を増やし，様々な臨床ステージの大腸がんのオルガノイド培養を樹立した．また，マウスへの異種移植により，in vivoでの管腔形成の評価が可能になった．こうした技術開発より，ヒト腸管上皮の管腔形成異常をin vitro，in vivoの双方で解析するシステムが確立された．さらに，オルガノイドの遺伝子変異の網羅的解析により，管腔構造形成異常を誘導する遺伝子について解明していきたい．
ウィルスベクタ－などの遺伝子操作技術が向上し，より自由度の高い，オルガノイドの遺伝子操作が可能になった．正常上皮細胞からの人工大腸がん誘導，細胞周期・幹細胞の蛍光可視化が実現しつつあり，今後，こうした技術を基に，腸管上皮細胞の時空間的な動態を数理学的モデルも含めて解明していきたい．
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| Current Status of Research Progress |
Reason
25年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
25年度が最終年度であるため、記入しない。
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Research Products
(29 results)
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[Journal Article] KLF5 regulates the integrity and oncogenicity of intestinal stem cells.2014
Author(s)
Nakaya T, Ogawa S, Manabe I, Tanaka M, Sanada M, Sato T, Taketo M, Nakao K, Clevers H, Fukayama M, Kuroda M, Nagai R.
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Journal Title
Cancer Res.
Volume: in press
Pages: in press
DOI
Peer Reviewed
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[Journal Article] Macrophages and Dendritic Cells Emerge in the Liver during Intestinal Inflammation and Predispose the Liver to Inflammation.2014
Author(s)
Mikami Y, Mizuno S, Nakamoto N, Hayashi A, Sujino T, Sato T, Kamada N, Matsuoka K, Hisamatsu T, Ebinuma H, Hibi T, Yoshimura A, Kanai T.
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Journal Title
PLoS One.
Volume: 9
Pages: e84619
DOI
Peer Reviewed
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[Journal Article] Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis.2013
Author(s)
Huch M, Bonfanti P, Boj SF, Sato T, Loomans CJ, van de Wetering M, Sojoodi M, Li VS, Schuijers J, Gracanin A, Ringnalda F, Begthel H, Hamer K, Mulder J, van Es JH, de Koning E, Vries RG, Heimberg H, Clevers H.
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Journal Title
EMBO J.
Volume: 32(20)
Pages: 2708-21
DOI
Peer Reviewed
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[Journal Article] Continuous low-dose irradiation by I-125 seeds induces apoptosis of gastric cancer cells regardless of histological origin.2013
Author(s)
Takabayashi K, Kashiwagi K, Kawata T, Sato T, Matsuoka K, Hisamatsu T, Takaishi H, Hibi T, Ogata H, Yahagi N, Kitagawa Y, Shigematsu N, Kanai T.
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Journal Title
Cancer Biol Ther.
Volume: 15(1)
Pages: 81-8
DOI
Peer Reviewed
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[Journal Article] A single strain of Clostridium butyricum induces intestinal IL-10-producing macrophages to suppress acute experimental colitis in mice.2013
Author(s)
Hayashi A, Sato T, Kamada N, Mikami Y, Matsuoka K, Hisamatsu T, Hibi T, Roers A, Yagita H, Ohteki T, Yoshimura A, Kanai T.
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Journal Title
Cell Host Microbe.
Volume: 13(6)
Pages: 711-22
DOI
Peer Reviewed
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[Journal Article] Mucosal healing with oral tacrolimus is associated with favorable medium- and long-term prognosis in steroid-refractory/dependent ulcerative colitis patients.2013
Author(s)
Miyoshi J, Matsuoka K, Inoue N, Hisamatsu T, Ichikawa R, Yajima T, Okamoto S, Naganuma M, Sato T, Kanai T, Ogata H, Iwao Y, Hibi T.
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Journal Title
J Crohns Colitis.
Volume: 7(12)
Pages: e609-14
DOI
Peer Reviewed
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[Journal Article] Establishment of novel prediction system of intestinal absorption in humans using human intestinal tissues.2013
Author(s)
Miyake M, Toguchi H, Nishibayashi T, Higaki K, Sugita A, Koganei K, Kamada N, Kitazume MT, Hisamatsu T, Sato T, Okamoto S, Kanai T, Hibi T.
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Journal Title
J Pharm Sci.
Volume: 102(8)
Pages: 2564-71
DOI
Peer Reviewed
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[Journal Article] TGR5 signalling inhibits the production of pro-inflammatory cytokines by in vitro differentiated inflammatory and intestinal macrophages in Crohn's disease.2013
Author(s)
Yoneno K, Hisamatsu T, Shimamura K, Kamada N, Ichikawa R, Kitazume MT, Mori M, Uo M, Namikawa Y, Matsuoka K, Sato T, Koganei K, Sugita A, Kanai T, Hibi T.
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Journal Title
Immunology
Volume: 139(1)
Pages: 19-29
DOI
Peer Reviewed
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[Journal Article] In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration.2013
Author(s)
Huch M, Dorrell C, Boj SF, van Es JH, Li VSW, van de Wetering M, Sato T, Hamer K, Sasaki N, Finegold MJ, Haft A, Vries R, Grompe M, Clevers H.
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Journal Title
Nature
Volume: 494(7436)
Pages: 247-50
DOI
Peer Reviewed
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