Phosphoproteome analysis of the liver tissues with NAFLD/NASH and identification of therapeutic targets.
Project/Area Number |
18H02793
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 53010:Gastroenterology-related
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Research Institution | Kanazawa University |
Principal Investigator |
HONDA Masao 金沢大学, 保健学系, 教授 (00272980)
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Co-Investigator(Kenkyū-buntansha) |
堀本 勝久 国立研究開発法人産業技術総合研究所, 生命工学領域, 招聘研究員 (40238803)
鍵和田 晴美 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (40443204)
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Project Period (FY) |
2018-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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Keywords | 非アルコール性脂肪性肝炎 / リン酸化 / プロテインアレイ / 肝癌 |
Outline of Final Research Achievements |
NASH is closely associated with the increase in lifestyle-related diseases and effective therapy to NASH is now under development. We developed high throughput phosphoproteome analysis system and examined liver tissues of mouse NSAH model and the patients of NASH. We identified 13 genes associated with NASH progressions and one of them was receptor of soluble factor. We also newly identified the hyper phospholylation of V-ATPase family genes in NASH-HCC. These genes could be new targets to prevent the progression of NASH and the therapy to treat NASH related HCC.
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Academic Significance and Societal Importance of the Research Achievements |
生活習慣病の増加と共に増加するNASHの成因は不明であり、有効な治療法は存在しない。申請者らは、ハイスループットで多検体のリン酸化解析を網羅的に解析する新技術プロテインアレイを確立し、マウスNASH肝発がんモデル及びNAFLD/NASH症例のリン酸化プロファイルを明らかにした。NASH病態の進行と関連する特に変動の大きな13遺伝子の中には、液性因子レセプターが含まれ、創薬の候補になり得ると考えられた。また、NASH肝癌の新たな治療標的分子としてV-ATPaseファミリー遺伝子を同定した。免疫チェックポイント阻害剤による治療に抵抗性を示すNASH肝癌の新たな治療標的として有望と考えられた。
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Report
(4 results)
Research Products
(77 results)
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[Journal Article] Hepatitis B Core-Related Antigen to Indicate High Viral Load: Systematic Review and Meta-Analysis of 10,397 Individual Participants2021
Author(s)
Yoshida K, Desbiolles A, Feldman SF, Ahn SH, Alidjinou EK, Atsukawa M, Bocket L, Brunetto MR, Buti M, Carey I, Caviglia GP, Chen EQ, Cornberg M, Enomoto M, Honda M, Tanaka Y, Shimakawa Y. etal
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Journal Title
Clinical Gastroenterology and Hepatology
Volume: 19
Issue: 1
Pages: 46-60.e8
DOI
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Peer Reviewed / Open Access
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[Journal Article] Serum laminin γ2 monomer as a novel diagnostic and predictive biomarker for hepatocellular carcinoma.2021
Author(s)
T Yamashita, N Koshikawa, T Shimakami, T Terashima, M Nakagawa, K Nio, R Horii, N Iida, K Kawaguchi, K Arai, Y Sakai, T Yamashita, E Mizukoshi, M Honda, A Kitao, S Kobayashi, S Takahara, Y Imai, K Yoshimura, T Murayama, Y Nakamoto, E Yoshida, T Yoshimura, M Seiki, S Kaneko.
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Journal Title
Hepatology
Volume: -
Issue: 2
Pages: 760-775
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Peer Reviewed / Open Access
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[Journal Article] Upregulation of the Long Noncoding RNA HULC by Hepatitis C Virus and Its Regulation of Viral Replication2020
Author(s)
Kitabayashi J, Shirasaki T, Shimakami T, Nishiyama T, Welsch C, Funaki M, Murai K, Sumiyadorj A, Takatori H, Kitamura K, Kawaguchi K, Arai K, Yamashita T, Sakai Y, Yamashita T, Mizukoshi E, Honda M, Kaneko S; Hokuriku Liver Study Group.
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Journal Title
The Journal of Infectious Diseases
Volume: -
Issue: 3
Pages: 407-419
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Peer Reviewed / Open Access
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[Journal Article] Comparative analysis of liver functional reserve during lenvatinib and sorafenib for advanced hepatocellular carcinoma.2020
Author(s)
Terashima T, Yamashita T, Takata N, Toyama T, Shimakami T, Takatori H, Arai K, Kawaguchi K, Kitamura K, Yamashita T, Sakai Y, Mizukoshi E, Honda M, Kaneko S.
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Journal Title
Hepatology Research
Volume: -
Issue: 7
Pages: 871-884
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Peer Reviewed / Open Access
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[Journal Article] Fatty acid-driven modifications in T-cell profiles in non-alcoholic fatty liver disease patients.2020
Author(s)
T Seike, E Mizukoshi, K Yamada, H Okada, M Kitahara, T Yamashita, K Arai, T Terashima, N Iida, K Fushimi, T Yamashita, Y Sakai, M Honda, K Harada, S Kaneko.
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Journal Title
J Gastroenterol
Volume: -
Issue: 7
Pages: 701-711
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Tumor lysis syndrome in a patient with metastatic melanoma treated with nivolumab2020
Author(s)
Sugimoto Saiho、Terashima Takeshi、Yamashita Tatsuya、Iida Noriho、Kitahara Masaaki、Hodo Yuji、Shimakami Tetsuro、Takatori Hajime、Arai Kuniaki、Kawaguchi Kazunori、Kitamura Kazuya、Yamashita Taro、Sakai Yoshio、Shirota Yukihiro、Sato Katsuaki、Mizukoshi Eishiro、Honda Masao、Harada Kenichi、Kaneko Shuichi
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Journal Title
Clinical Journal of Gastroenterology
Volume: 13
Issue: 5
Pages: 935-939
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Peer Reviewed / Open Access
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[Journal Article] IL-28B variant as a predictor in patients with advanced hepatocellular carcinoma treated with hepatic arteiral infusion chemotherapy.2020
Author(s)
Terashima T, Honda M, Toyama T, Shimakami T, Shimizu R, Takatori H, Arai K, Kawaguchi K, Kitamura K, Yamashita T, Sakai Y, Yamashita T, Mizukoshi E, Kaneko S.
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Journal Title
Journal of Gastroenterology and Hepatology
Volume: -
Issue: 10
Pages: 1813-1820
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Peer Reviewed / Open Access
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[Journal Article] DOCK11 and DENND2A play pivotal roles in the maintenance of hepatitis B virus in host cells.2020
Author(s)
Hashimoto S, Shirasaki T, Yamashita T, Iwabuchi S, Suzuki Y, Takamura Y, Ukita Y, Deshimaru S, Okayama T, Ikeo K, Kuroki K, Kawaguchi K, Mizukoshi E, Matsushima K, Honda M, Kaneko S
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Journal Title
PLoS One
Volume: 16(2)
Issue: 2
Pages: e0246313-e0246313
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[Journal Article] Characteristics of impaired dendritic cell function in patients with hepatitis B virus infection.2019
Author(s)
Yonejima A, Mizukoshi E, Tamai T, Nakagawa H, Kitahara M, Yamashita T, Arai K, Terashima T, Iida N, Fushimi K, Okada H, Yamashita T, Sakai Y, Honda M, Kaneko S.
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Journal Title
Hepatology
Volume: 10.1002/hep
Issue: 1
Pages: 30637-30637
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Peer Reviewed / Open Access
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[Journal Article] Induction of Selenoprotein P mRNA during Hepatitis C Virus Infection Inhibits RIG-I-Mediated Antiviral Immunity.2019
Author(s)
Murai K, Honda M, Shirasaki T, Shimakami T, Omura H, Misu H, Kita Y, Takeshita Y, Ishii KA, Takamura T, Urabe T, Shimizu R, Okada H, Yamashita T, Sakai Y, Kaneko S.
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Journal Title
Cell Host Microbe
Volume: 10;25(4)
Issue: 4
Pages: 588-601
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Peer Reviewed / Open Access
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[Journal Article] Serum C16:1n7/C16:0 ratio as a diagnostic marker for non-alcoholic steatohepatitis.2019
Author(s)
K Yamada, E Mizukoshi, T Seike, R Horii, T Terashima, N Iida, M Kitahara, H Sunagozaka, K Arai, T Yamashita, M Honda, T Takamura, K Harada, S Kaneko.
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Journal Title
J Gastroenterol Hepatol
Volume: 34
Issue: 10
Pages: 1829-1835
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Peer Reviewed / Open Access
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[Journal Article] Distinct chemotherapy-associated anti-cancer immunity by myeloid cells inhibition in murine pancreatic cancer models.2019
Author(s)
Sakai Y, Miyazawa M, Komura T, Yamada T, Nasti A, Yoshida K, Takabatake H, Yamato M, Yamashita T, Yamashita T, Mizukoshi E, Okuzono M, Ho TTB, Kawaguchi K, Wada T, Honda M, Kaneko S.
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Journal Title
Cancer Sci
Volume: 110
Issue: 3
Pages: 903-912
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Three renal failure cases successfully treated with ombitasvir/paritaprevir/ritonavir for genotype 1b hepatitis C virus reinfection after liver transplantation.2019
Author(s)
Orita N, Shimakami T, Sunagozaka H, Horii R, Nio K, Terashima T, Iida N, Kitahara M, Takatori H, Kawaguchi K, Kitamura K, Arai K, Yamashita T, Sakai Y, Yamashita T, Mizukoshi E, Honda M, Kaneko S.
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Journal Title
Clin J Gastroenterol
Volume: 12
Issue: 1
Pages: 63-70
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Peer Reviewed / Open Access
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[Journal Article] Characteristics of Immune Response to Tumor‐Associated Antigens and Immune Cell Profile in Patients With Hepatocellular Carcinoma.2019
Author(s)
Y Inada, E Mizukoshi, T Seike, T Tamai, N Iida, M Kitahara, T Yamashita, K Arai, T Terashima, K Fushimi, T Yamashita, M Honda, S Kaneko.
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Journal Title
Hepatology
Volume: 69
Issue: 2
Pages: 653-665
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[Journal Article] Serum aldo-keto reductase family 1 member B10 predicts advanced liver fibrosis and fatal complications of nonalcoholic steatohepatitis.2019
Author(s)
M Kanno, K Kawaguchi, M Honda, R Horii, H Takatori, T Shimakami, K Kitamura, K Arai, T Yamashita, Y Sakai, T Yamashita, E Mizukoshi, S Kaneko.
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Journal Title
J Gastroenterol
Volume: -
Issue: 6
Pages: 549-557
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[Journal Article] Biological characteristics of gene expression features in pancreatic cancer cells induced by proton and X-ray irradiation.2018
Author(s)
Fujinaga H, Sakai Y, Yamashita T, Arai K, Terashima T, Komura T, Seki A, Kawaguchi K, Nasti A, Yoshida K, Wada T, Yamamoto K, Kume K, Hasegawa T, Takata T, Honda M, Kaneko S.
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Journal Title
Int J Radiat Biol
Volume: 17
Issue: 5
Pages: 1-9
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Peer Reviewed / Open Access
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[Journal Article] Analysis of the liver functional reserve of patients with advanced hepatocellular carcinoma undergoing sorafenib treatment: Prospects for regorafenib therapy.2018
Author(s)
Terashima T, Yamashita T, Sunagozaka H, Arai K, Kawaguchi K, Kitamura K, Yamashita T, Sakai Y, Mizukoshi E, Honda M, Kaneko S.
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Journal Title
Hepatol Res
Volume: 48
Issue: 12
Pages: 956-966
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[Journal Article] Prevention of hepatocellular carcinoma by targeting MYCN-positive liver cancer stem cells with acyclic retinoid2018
Author(s)
Qin XY, Suzuki H, Honda M, Okada H, Kaneko S, Inoue I, Ebisui E, Hashimoto K, Carninci P, Kanki K, Tatsukawa H, Ishibashi N, Masaki T, Matsuura T, Kagechika H, Toriguchi K, Hatano E, Shirakami Y, Shiota G, Shimizu M, Moriwaki H, Kojima S
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Journal Title
Proc Natl Acad Sci U S A
Volume: 115
Issue: 19
Pages: 4969-4974
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[Journal Article] Genome-wide association study identified new susceptible genetic variants in HLA class I region for hepatitis B virus-related hepatocellular carcinoma2018
Author(s)
awai H, Nishida N, Sugiyama M, Murata K, Hino K, Nishina S, Matsumoto A, Tanaka E, Sakamoto N, Ogawa K, Yamamoto K, Tamori A, Yokosuka O, Kanda T, Sakaida I, Itoh Y, Eguchi Y, Oeda S, Mochida S, Yuen MF, Seto WK, Poovorawan Y, Posuwan N, Mizokami M, Tokunaga K
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Journal Title
Sci Rep
Volume: 8
Issue: 1
Pages: 7958-7958
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[Journal Article] Unexpected Replication Boost by Simeprevir for Simeprevir-resistant Variants in Genotype 1a Hepatitis C Virus2018
Author(s)
Murai K, Shimakami T, Welsch C, Shirasaki T, Liu F, Kitabayashi J, Tanaka S, Funaki M, Omura H, Nishikawa T, Suminyadorj A, Honda M, Kaneko S.
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Journal Title
Antimicrob Agents Chemother
Volume: 印刷中
Issue: 7
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[Journal Article] Immune Condition of Colorectal Cancer Patients Featured by Serum Chemokines and Gene Expressions of CD4+ Cells in Blood.2018
Author(s)
Komura T, Yano M, Miyake A, Takabatake H, Miyazawa M, Ogawa N, Seki A, Honda M, Wada T, Matsui S, Kaneko S, Sakai Y.
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Journal Title
Can J Gastroenterol Hepatol
Volume: 7436205
Pages: 1-9
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[Journal Article] The osteopontin-CD44 axis in hepatic cancer stem cells regulates IFN signaling and HCV replication.2018
Author(s)
Shirasaki T, Honda M, Yamashita T, Nio K, Shimakami T, Shimizu R, Nakasyo S, Murai K, Shirasaki N, Okada H, Sakai Y, Sato T, Suzuki T, Yoshioka K, Kaneko S.
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Journal Title
Sci Rep.
Volume: 8
Issue: 1
Pages: 13143-13143
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[Journal Article] Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein predicts hepatocellular carcinoma incidence and recurrence in nucleos(t)ide analogue therapy for chronic hepatitis B.2017
Author(s)
Kawaguchi K, Honda M, Ohta H, Terashima T, Shimakami T, Arai K, Yamashita T, Sakai Y, Yamashita T, Mizukoshi E, Komura T, Unoura M, Kaneko S
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Journal Title
J Gastroenterol
Volume: ePub ahead
Issue: 6
Pages: 740-751
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[Presentation] Annual decline in serum albumin concentration is a predictor of serious events in non-alcoholic fatty liver disease -a retrospective multicenter study2020
Author(s)
Kazunori Kawaguchi, Yoshio Sakai, Takeshi Terashima, Akihiro Seki, Tetsuro Shimakami, Hajime Takatori, Kuniaki Arai, Kazuya Kitamura, Taro Yamashita, Tatsuya Yamashita, Eishiro Mizukoshi, Masao Honda, Shuichi Kaneko
Organizer
AASLD2020
Related Report
Int'l Joint Research
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[Presentation] Dynamics of Programmed cell death-1 in peripheral blood immune cell profiles and RNA-seq analysis of chronic hepatitis C patients treated with direct-acting antivirals2020
Author(s)
Miyabi Miura, Kazunori Kawaguchi, Eishiro Mizukoshi, Kiichiro Kaji, Toshikatsu Tamai, Hidetoshi Nakagawa, Takeshi Terashima, Masaaki Kitahara,Noriho Iida, Tetsuro Shimakami, Kuniaki Arai, Taro Yamashita, Yoshio Sakai, Tatsuya Yamashita, Masao Honda, Shuichi Kaneko
Organizer
AASLD2020
Related Report
Int'l Joint Research
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[Presentation] Serum aldo-keto reductase family 1 member B10 predicts HBV-related hepatocellular carcinoma during nucleos(t)ide analogue treatment2019
Author(s)
Kazunori Kawaguchi, Masao Honda, Noriaki Orita, Masataka Kanno, Rika Horii, Kouki Nio, Takeshi Terashima, Tetsuro Shimakami, Kuniaki Arai, Taro Yamashita, Yoshio Sakai, Tatsuya Yamashita, Eishiro Mizukoshi, Shuichi Kaneko
Organizer
AASLD2019
Related Report
Int'l Joint Research
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[Presentation] Characteristics and Functional Regulation of Dendritic Cells in Hepatitis B Patients2018
Author(s)
Atsushi Yonejima, Eishiro Mizukoshi, Kiichiro Kaji, Toshikatsu Tamai, Hidetoshi Nakagawa, Takeshi Terashima, Noriho Iida, Masaaki Kitahara, Kuniaki Arai, Tatsuya Yamashita, Masao Honda, Shuichi Kaneko
Organizer
AASLD2018
Related Report
Int'l Joint Research
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[Presentation] Immune response to tumor-associated antigens and immune vell profiles in NASH-related hepatocellular carcinoma2018
Author(s)
Takuya Seike, Eishiro Mizukoshi, Yuki Inada, Toshikatsu Tamai, Noriho Iida, Masaaki Kitahara, Tatsuya Yamashita, Kuniaki Arai, Takeshi Terashima, Taro Yamashita, Masao Honda, Shuichi Kaneko
Organizer
AASLD2018
Related Report
Int'l Joint Research
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[Presentation] Elevation of serum aldo-keto reductase family 1 member B10 is associated with advanced liver fibrosis in non-alcoholic steatohepatitis2018
Author(s)
Kanno Masataka, Kazunori Kawaguchi, Masao Honda, Rika Horii, Hajime Takatori, Tetsuro Shimakami, Kazuya Kitamura, Kuniaki Arai, Taro Yamashita, Yoshio Sakai, Tatsuya Yamashita, Eishiro Mizukoshi, Shuichi Kaneko
Organizer
AASLD2018
Related Report
Int'l Joint Research