Suppression of alpha-fetoprotein related hepatocellular proliferation and hepatocellular carcinogenesis in nonalcoholic steatohepatitis
| Project/Area Number |
24590981
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kochi University |
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Principal Investigator |
SAIBARA Toshiji 高知大学, 教育研究部医療学系, 教授 (60145125)
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| Co-Investigator(Kenkyū-buntansha) |
TODA Katsumi 高知大学, 教育研究部医療学系, 准教授 (40197893)
ONO Masafumi 高知大学, 教育研究部医療学系, 講師 (70304681)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 肝臓学 / NASH / 肝発癌 / エストロゲン / PPAR-α / 非アルコール性脂肪性肝疾患 / 非アルコール性脂肪肝炎 / NASH動物モデル / 肥満 / 肝細胞癌 / AFP / MC4R / α-fetoprotein |
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| Outline of Final Research Achievements |
Aromatase deficient mice develop hepatic steatosis spontaneously via enhanced lipogenesis with increased glyconeogenesis. PPAR-α expression is decreased in this model and it recovers gradually after exogenous estrogen and/or PPAR-α ligand administration. Impaired PPAR-αexpression is a risk factor for the development of diabetes and hepatic steatosis in the hepatocarcinogenic model using these mice. PPAR-α expression in these mice recovered spontaneously in the liver with chronic inflammation and hepatocellular carcinoma emerged afterward. The frequency of hepatocarcinogenesis in these mice is suppressed when PPAR-α is deficient. These observation suggest that PPAR-α activation mediated process is involved profoundly in the hepatocarcinogenesis in these mice and that estrogen could affect this process to suppress the carcinogenesis efficiently.
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Report
(4 results)
Research Products
(122 results)
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[Journal Article] Evaluation of Ki-67 index in EUS-FNA specimens for the assessment of malignancy risk in pancreatic neuroendocrine tumors.2014
Author(s)
Hasegawa T, Yamao K, Hijioka S, Bhatia V, Mizuno N, Hara K, Imaoka H, Niwa Y, Tajika M, Kondo S, Tanaka T, Shimizu Y, Kinoshita T, Kohsaki T, Nishimori I, Iwasaki S, Saibara T, Hosoda W, Yatabe Y
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Journal Title
Endoscopy
Volume: 46(1)
Issue: 01
Pages: 32-38
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Simple scoring system for predicting cirrhosis in nonalcoholic fatty liver disease.2014
Author(s)
Kessoku T, Ogawa Y, Yoneda M, Imajo K, Sumida Y, Eguchi Y, Fujii H, Hyogo H, Ono M, Suzuki Y, Kawaguchi T, Chayama K, Tanaka S, Fujimoto K, Anzai K, Saibara T, Sata M, Itoh Y, Nakajima A, Okanoue T
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Journal Title
World J Gastroenterol
Volume: 20（29）
Issue: 29
Pages: 10108-10114
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Multicenter validation study of anti-programmed cell death-1 antibody as a serological marker for type 1 autoimmune hepatitis.2014
Author(s)
Miyake Y, Yamamoto K, Matsushita H, Abe M, Takahashi A, Umemura T, Tanaka A, Nakamuta M, Nakamoto Y, Ueno Y, Saibara T, Takikawa H, Yoshizawa K, Ohira H, Zeniya M, Onji M, Tsubouchi H; Intractable Liver and Biliary Diseases Study Group of Japan
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Journal Title
Hepatol Res.
Volume: in press
Issue: 13
Pages: 1299-1307
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Autoantibody status and histological variables influence biochemical response to treatment and long-term outcomes in Japanese patients with primary biliary cirrhosis.2014
Author(s)
Nakamura M, Kondo H, Tanaka A, Komori A, Ito M, Yamamoto K, Ohira H, Zeniya M, Hashimoto E, Honda M, Kaneko S, Ueno Y, Kikuchi K, Shimoda S, Harada K, Arai K, Miyake Y, Abe M, Taniai M, Saibara T, Sakisaka S, Takikawa H, Onji M, Tsubouchi H, Nakanuma Y, Ishibashi H.
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Journal Title
Hepatol Res.
Volume: -
Issue: 8
Pages: 846-855
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Safety and efficacy of image-guided enzyme-targeting radiosensitization and intraoperative radiotherapy for locally advanced unresectable pancreatic cancer.2014
Author(s)
Nishioka A, Ogawa Y, Miyatake K, Tadokoro M, Nogami M, Hamada N, Kubota K, Kariya S, Kohsaki T, Saibara T, Okabayashi T, Hanazaki K.
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Journal Title
Oncol Lett
Volume: 8(1)
Pages: 404-408
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Type 2 diabetes mellitus is associated with the fibrosis severity in patients with nonalcoholic fatty liver disease in a large retrospective cohort of Japanese patients.2014
Author(s)
Nakahara T, Hyogo H, Yoneda M, Sumida Y, Eguchi Y, Fujii H, Ono M, Kawaguchi T, Imajo K, Aikata H, Tanaka S, Kanemasa K, Fujimoto K, Anzai K, Saibara T, Sata M, Nakajima A, Itoh Y, Chayama K, Okanoue T
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Journal Title
J Gastroenterol
Volume: 49(11)
Issue: 11
Pages: 1477-1484
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The association of insomnia with gastroesophageal reflux symptoms in biopsy-proven nonalcoholic fatty liver disease.2014
Author(s)
Taketani H, Sumida Y, Tanaka S, Imajo K, Yoneda M, Hyogo H, Ono M, Fujii H, Eguchi Y, Kanemasa K, Chayama K, Itoh Y, Yoshikawa T, Saibara T, Fujimoto K, Nakajima A
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Journal Title
J Gastroenterol
Volume: 49(7)
Issue: 7
Pages: 1163-1174
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Bofutsushosan, a Japanese herbal (Kampo) medicine, attenuates progression of nonalcoholic steatohepatitis in mice2013
Author(s)
Masafumi Ono, Mitsunari Ogasawara, Akira Hirose, Sachiko Mogami, Nobuhiro Ootake, Kosuke Aritake, Takuma Higuchi, Nobuto Okamoto, Shuji Sakamoto, Masahiro Yamamoto, Yoshihiro Urade, Toshiji Saibara, Jude A. Oben.
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Journal Title
Journal of Gastroenterology
Volume: 49(6)
Issue: 6
Pages: 1065-1173
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The association of insomnia with gastroesophageal reflux symptoms in biopsy-proven nonalcoholic fatty liver disease.2013
Author(s)
Taketani H, Sumida Y, Tanaka S, Imajo K, Yoneda M, Hyogo H, Ono M, Fujii H, Eguchi Y, Kanemasa K, Chayama K, Itoh Y, Yoshikawa T, Saibara T, Fujimoto K, Nakajima A; Japan Study Group of NAFLD (JSG-NAFLD).
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Journal Title
J Gastroenterol
Volume: in press
Related Report
Peer Reviewed
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[Journal Article] Hepatocyte destruction with enhanced collagen synthesis: Characteristic feature of chronic hepatitis C patients on haemodialysis2013
Author(s)
Ue, M., Ikebe, N., Munekage, K., Ochi, T., Hirose, A., Kataoka, H., Fujimoto, S., Kikuchi, K., Okuhara, Y., Ono, M.a , Saibara, T.
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Journal Title
Journal of Viral Hepatitis
Volume: 20(6)
Issue: 5
Pages: 350-357
DOI
Related Report
Peer Reviewed
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[Journal Article] Validation of the FIB4 index in a Japanese nonalcoholic fatty liver disease population2012
Author(s)
Sumida Y, Yoneda M, Hyogo H, Itoh Y, Ono M, Fujii H, Eguchi Y, Suzuki Y, Aoki N, Kanemasa K, Fujita K, Chayama K, Saibara T, Kawada N, Fujimoto K, Kohgo Y, Yoshikawa T, Okanoue T, Jsg-Nafld JS
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Journal Title
BMC Gastroenterol
Volume: (Epub)
Issue: 1
Pages: 2-2
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Clinical and pathological progression of non-alcoholic steatohepatitis to hepatocellular carcinoma2012
Author(s)
Yasui K, Hashimoto E, Tokushige K, Koike K, Shima T, Kanbara Y, Saibara T, Uto H, Takami S, Kawanaka M, Komorizono Y, Okanoue T, and The Japan NASH Study Group.
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Journal Title
Hepatol Res
Volume: 42
Issue: 8
Pages: 767-773
DOI
Related Report
Peer Reviewed
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[Presentation] The association of insomnia with gastroesophageal reflux symptoms in biopsy-proven nonalcoholic fatty liver disease．2013
Author(s)
Taketani H, Sumida Y, Tanaka S, Kanemasa K, Yoneda M, Imajo K, Nakajima A, Hyogo H, Chayama K, Ono M, Saibara T, Fujii H, Eguchi Y, Itoh Y
Organizer
AASLD 2013
Place of Presentation
Walter E. Washington convention center ( Washington USA)
Related Report
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[Presentation] Glycemic variability is an independent predictive factor for development of hepatic fibrosis in nonalcoholic fatty liver disease．2013
Author(s)
Ochi T, Hashiba M, Ono M, Hyogo H, Ikeda Y, Munekage K, Okamoto N, Iwasaki S, Chayama K, Eguchi Y, Saibara T
Organizer
The 64th Annual Meeting of the American Association for the Study of Liver Diseases 2013
Place of Presentation
Walter E. Washington convention center ( Washington USA)
Related Report
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