Nrf2 activation inhibits steatohepatitis and liver cancer in overeating-induced obese mice.
| Project/Area Number |
25293278
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
NAKAYAMA MASAMITI 東京女子医科大学, 医学部, 講師 (00338980)
YANAGAWA TORU 筑波大学, 医学医療系, 准教授 (10312852)
YAMAMOTO MASAKAZU 東京女子医科大学, 医学部, 教授 (60220498)
UTSUNOMIYA HIROTOSHI 和歌山県立医科大学, 共同利用施設, 准教授 (60264876)
GOTO NAOHIRO 東京海洋大学, 海洋科学技術研究科, 准教授 (60323854)
WARABI EIJI 筑波大学, 医学医療系, 講師 (70396612)
SHODA JUNNICHI 筑波大学, 医学医療系, 教授 (90241827)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2013: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
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| Keywords | 肥満 / 脂肪性肝炎 / 肝発癌 / 転写因子 / 動物モデル / Nrf2 |
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| Outline of Final Research Achievements |
We generated double knockout (DKO) mice without Sqstm1 and Nrf2 genes. To confirm a hypothesis for bacteria-induced metabolic liver disease, we focused on the endotoxin produced by Gram-negative bacteria. In DKO mice, severe NASH was developed with the pathological state of steatohepatitis after 30 weeks. The serum endotoxin levels were significantly higher in DKO mice than those in WT mice. Furthermore, the intestinal permeability, and the gram-negative bacteria levels and endotoxin in feces were all increased significantly in DKO mice. DKO mice had a significant decrease in Kupffer cells (KCs)’ phagocytic function compared with WT. The overload of serum endotoxin induced by the modification of intestine microbiota, the increase of intestinal permeability and the impaired clearance of LPS by KCs dysfunction were considered to be important for the progression of NASH in DKO mice. DKO mouse is a novel animal model that develops mature-onset NASH.
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Report
(4 results)
Research Products
(119 results)
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[Journal Article] Overexpression and gene amplification of EGFR, HER2,ond HER3 in biliary tract carcinomas,and the possibility for therapy with the HER2-trageting antibody pertuzumab.2015
Author(s)
Kawamoto T, Ishige K, Tomas M, Yamashita Y, Shu S, Ishikura N, Ariizumi S, Yamamoto M, Kurosaki K, Shoda J.
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Journal Title
J Gastroenterol
Volume: 50
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[Journal Article] Whole-genome mutational landscape of liver cancers displaying biliary phenotype reveals hepatitis impact and molecular diversity.2015
Author(s)
Fujimoto A, Furuta M, Shiraishi Y, Gotoh K, Kawakami Y, Arihiro K, Nakamura T, Ueno M, Ariizumi S, Ha HN, Shigemizu D, Abe T, Keith A. B, Nakano K, Sasaki A, Kitada R maejima K, Yamamoto Y, Tanaka H, Shibuya T, Shibata T, Ojima H, Shimada K, Hayami S, Shigekawa Y, Aikata H, Ohdan H, Marubashi S.
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Nature Communications
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Pages: 6120-6127
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Author(s)
羽鳥隆, 鈴木修司, 大島奈々, 鈴木隆二, 君島映, 出雲渉, 古川徹, 田原純子, 高山敬子, 清水京子, 白鳥敬子, 三橋紀夫, 山本雅一
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Journal Title
胆と膵
Volume: 35
Pages: 43-47
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] 特集 膵癌に対する術前治療をめぐって2014
Author(s)
羽鳥隆, 鈴木修司, 大島奈々, 鈴木隆二, 君島映, 出雲渉, 古川徹, 田原純子, 高山敬子, 清水京子, 白鳥敬子, 三橋紀夫, 山本雅一*
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Journal Title
胆と膵
Volume: 35
Pages: 43-47
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] 特集 消化器外科におけるチーム医療 食道癌治療におけるチーム医療の現状と展望2014
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成宮孝祐, 太田正穂, 工藤健司, 佐藤拓也, 白井雄史, 金子由香, 伊藤俊一, 堀部達也, 工藤弦, 菊地剛, 山中昭広, 井手博子, 小谷透, 山本雅一
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Journal Title
消化器外科
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Pages: 335-341
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植村修一郎, 有泉俊一, 高橋豊, 大森亜紀子, 小寺由人, 片桐聡, 橋本悦子, 中野雅行, 山本雅一
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Journal Title
日本消化器病学会雑誌
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[Journal Article] Clinicopathological characterization of so-called "cholangiocarcinoma with intraductal papillary growth" with respect to "intraductal papillary neoplasm of bile duct (IPNB)".2014
Author(s)
Nakanuma Y, Sato Y, Ojima H, Kanai Y, Aishima S, Yamamoto M, Ariizumi S, Furukawa T, Hayashi H, Unno M, Ohta T
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Journal Title
International Journal of Clinical and Experimental Pathology
Volume: 7
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Acceleration training for management of non-alcoholic fatty liver disease: a pilot study.2014
Author(s)
Oh S, Shida T, Onozuka T, Maruyama T, Eguchi K, Isobe T, Okamoto Y, Someya N, Tanaka K, Tozawa A, Arai E, Shoda J.
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Ther Clin Risk Manag
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[Journal Article] Peroxidoxin I plays a ptotective role against UVA irradiation through reduction of oxidative stress.2014
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Ito T, Kimura S, Seto K, Warabi E, Kawauchi Y, Shoda J, Tabuchi K, Yamagata K, Hasegawa S, Bukawa H, Ishii T, Yanagawa T.
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Expression of N-acetylglucosaminyltransferase V in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder.2014
Author(s)
Onuki, K., Sugiyama, H., Ishige, K., Kawamoto, T., Ota, T., Ariizumi, S., Yamato, M., Kadota, S., Takeuchi, K., Ishikawa, A., Onodera, M., Onizawa, K., Yamamoto, M., Miyoshi, E., Shoda, J.
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Journal Title
J Gastroenterol
Volume: 49
Pages: 702-714
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Expression of N-acetylglucosaminyltransferase V in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder.2013
Author(s)
Onuki K, Sugiyama H, Ishige K, Kawamoto T, Ota T, Ariizumi S, Yamato M, Kadota S, Takeuchi K, Ishikawa A, Onodera M, Onizawa K, Yamamoto M, Miyoshi E, Shoda J
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Journal Title
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Volume: 49
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[Journal Article] Deficiency of p62/Sequestosome 1 causes hyperphagia due to leptin resistance in the brain2013
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[Journal Article] Novel virtual hepatectomy is useful is for evaluation of the portal territory for anatomical sectionectomy,segmentsctomy,and hemihepatectomy2013
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山本雅一
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ANAクラウンプラザホテル広島（広島県広島市）
Year and Date
2014-07-02
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[Presentation] （シンポジウム1 早期肝細胞癌の基礎・診断・治療・予後）Glypican3陽性の早期肝細胞癌は二次発癌が高率である2014
Author(s)
有泉俊一, ChenI-pei, 片桐聡, 小寺由人, 高橋豊, 大森亜紀子, 山下信吾, 尾形哲, 江川裕人, 中野雅行, 山本雅一
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第50回日本肝癌研究会
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Year and Date
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Author(s)
有泉俊一, 片桐聡, 小寺由人, 高橋豊, 大森亜紀子, 山下信吾, 尾形哲, 江川裕人, 中野雅行, 斎藤明子, 山本雅一
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[Presentation] Master-class liver operations2014
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Master class on "The trestment of HCC"
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Shimkent, Kazakhstan
Year and Date
2014-05-01
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[Presentation] 多血性早期肝細胞癌の1例2014
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Year and Date
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