Analysis of epigenetic changes via histone modification in liver cancer and development of new therapeutic strategy
Project/Area Number |
15K09021
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Keio University |
Principal Investigator |
SAITO Hidetsugu 慶應義塾大学, 薬学部(芝共立), 教授 (80186949)
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Research Collaborator |
KAMADA Nobuhiko University of Michigan, Center for Microbial Systems
SAITO Yoshimasa
MASHINO Tadahiko
KIMURA Masaki
YAMADA Shoji
NAKAOKA Toshiaki
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 脂肪性肝炎 / 肝発癌 / エピジェネティック変化 / mTOR / Nrf-2 / EZH2 / microRNA-122 / 高脂肪食摂餌 / 肝細胞癌 / Nrf2 / HCV / NASH / 高脂肪食STHD-01 / 長鎖飽和脂肪酸 / 腸内細菌 / 胆汁酸 / brusatol / miR-122 |
Outline of Final Research Achievements |
The main cause of hepatocarcinogenesis in Japan has been changing from viral infection to fatty liver diseases. The hepatic pathogenesis in fatty liver diseases is considered to be induced by dietary environmental change and this fact indicated that epigenetic change is an important factor in this disease entity. We refined Nrf-2, EZH2 and microRNA-122 as pathogenetic factors from the analyses of HCV particle producing cell line HPI and a murine model STAM. Moreover, we focused on a C57BL/6 model which develops hepatoma with only a high fat diet without giving any chemical carcinogens, and obtained an important result from this murine model that a component change of bile acids metabolized by intestinal microbiota and a consequent activation of mTOR pathway were most notable pathogenetic factors. Nrf-2, EZH2 and microRNA were also changed in this model, and these results reflected in vitro aspects.
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Report
(4 results)
Research Products
(49 results)
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[Journal Article] Commensal Lactobacillus controls immune tolerance during acute liver injury in mice2017
Author(s)
Nakamoto N, Amiya T, Aoki R, Taniki N, Koda Y, Miyamoto K, Teratani T, Suzuki T, Chiba S, Chu PS, Hayashi A, Yamaguchi A, Shiba S, Miyake R, Katayama T, Suda W, Mikami Y, Kamada N, Ebinuma H, Saito H, Hattori M, Kanai T
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Journal Title
Cell Reports
Volume: 5
Issue: 5
Pages: 1215-1226
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Genotype-associated differential NKG2D expression on CD56+CD3+lymphocytes predicts response to pegylated-Interferon/ribavirin therapy in chronic hepatitis C.2015
Author(s)
Chu P S, Ebinuma H, Nakamoto N, Sugiyama K, Usui S, Wakayama Y, Taniki N, Yamaguchi A, Shiba S, Yamagishi Y, Wakita T, Hibi T, Saito H, Kanai T.
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Journal Title
PLoS One
Volume: 10
Issue: 5
Pages: e0125664-e0125664
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Decrease of platelet count predicts de novo hepatocellular carcinoma in chronic hepatitis B patients who achieved sustained virological effect under long-term nucleus(t)ide analogues.2017
Author(s)
Miyake R, Chu P-S, Ikura A, Takeda K, Ugamura A, Shiba S, Yamaguchi A, Taniki N, Nakamoto N, Saito H, Kanai T.
Organizer
AASLD The Liver Meeting 2017
Related Report
Int'l Joint Research
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[Presentation] Nicotinamide N-methyltransferase regulates hepatic immunity via gut-liver axis2017
Author(s)
Taniki N, Nakamoto N, Mikami Y, Chu P-S, Ugamura A, Shiba S, Miyake R, Yamaguchi A, Amiya T, Ebinuma H, Saito H, Kanai T.
Organizer
AASLD The Liver Meeting 2017
Related Report
Int'l Joint Research
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[Presentation] Integrated collaboration of intestinal microbiota induces bacterial translocation and Th17 immune response in primary sclerosis cholangitis2017
Author(s)
Nakamoto N, Aoki R, Sasaki N, Taniki N, Chu P-S, Yamaguchi A, Shiba S, Saito H, Sato T, Kanai, T.
Organizer
AASLD The Liver Meeting 2017
Related Report
Int'l Joint Research
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