NAFLD/NASH肝組織リン酸化活性プロファイリングと新規治療標的分子の同定

• Project/Area Number: 18H02793
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kanazawa University
• Principal Investigator: 本多 政夫 金沢大学, 保健学系, 教授 (00272980)
• 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)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Granted (Fiscal Year 2020)
• Budget Amount: ¥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)
• 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

Outline of Annual Research Achievements

申請者らは世界最大のヒトタンパク質発現リソースHuPEX (Human Proteome Expression Resource)（約2万種）を基に高操作性・ハイスループットなプロテインアレイを作製し、正味のチロシンキナーゼ活性を高感度に測定する系を初めて確立した。本研究目的は新技術プロテインアレイを用いて、NAFLD/NASH肝組織のリン酸化プロファイルを明らかにして新規治療標的を同定する。
本年度はAth+HFDマウス肝組織の12週（Ath+HFD：5サンプル、コントロール：5サンプル）、30週（Ath+HFD：5サンプル、コントロール：5サンプル）、60週（Ath+HFD：5サンプル、コントロール：5サンプル）のリン酸化アレイを行った。1377個のリン酸化タンパクを標的とし、1サンプルあたり、6回の測定を行い、計180アレイの解析を行った。コントロールと比較し、12週では137個(p<0.005)、30週では154個(p<0.005)、60週では36個(p<0.005)の遺伝子のリン酸化変動が認められた。60週ではむしろ変動遺伝子の低下が認められ、炎症シグナルの減弱によるものと推察された。12週から60週までの全てを対象とした場合、変動遺伝子は203個（上昇：148個、低下：55個）(p<0.005)であった。発現上昇する遺伝子のパスウェイ解析では1）WNTシグナル、2）ケモカインシグナル、3）TGF-βシグナル、4）神経ペプチドシグナルの活性化が認められた。一方、発現低下する遺伝子のパスウェイ解析では1）血管新生制御、2）細胞接着、3）好中球活性化制御が認められた。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。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

Ath+HFDマウス肝組織のリン酸化アレイを実施し、標的リン酸化蛋白の候補を同定した。また、ヒトNASH肝組織におけるリン酸化プロファイルを施行中である。

Strategy for Future Research Activity

申請者らは世界最大のヒトタンパク質発現リソースHuPEX (Human Proteome Expression Resource)（約2万種）を基に高操作性・ハイスループットなプロテインアレイを作製し、正味のチロシンキナーゼ活性を高感度に測定する系を初めて確立した。本研究目的は新技術プロテインアレイを用いて、NAFLD/NASH肝組織のリン酸化プロファイルを明らかにして新規治療標的を同定する。
本年度はAth+HFDマウス肝組織の12週（Ath+HFD：5サンプル、コントロール：5サンプル）、30週（Ath+HFD：5サンプル、コントロール：5サンプル）、60週（Ath+HFD：5サンプル、コントロール：5サンプル）のリン酸化アレイを行った。1377個のリン酸化タンパクを標的とし、1サンプルあたり、6回の測定を行い、計180アレイの解析を行った。現在、ヒトNASH肝組織手術サンプル（20症例：癌部・非癌部）の解析を実施中であり、マウスの結果との比較を行う。マウスモデル解析では液性因子レセプターが同定されたことから、液性因子レセプター抗体を用いた in vitro及びin vivoでの検証を行う。

Research Products

• [Journal Article] A novel α-fetoprotein-derived helper T-lymphocyte epitope with strong immunogenicity in patients with hepatocellular carcinoma (2020)
  • Author(s): Tamai Toshikatsu、Mizukoshi Eishiro、Kumagai Masashi、Terashima Takeshi、Iida Noriho、Kitahara Masaaki、Shimakami Tetsuro、Kitamura Kazuya、Arai Kuniaki、Yamashita Taro、Sakai Yoshio、Yamashita Tatsuya、Honda Masao、Fushimi Kazumi、Kaneko Shuichi
  • Journal Title: Scientific reports Volume: 10 Pages: 4021-4021
  • DOI: 10.1038/s41598-020-60843-4
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: Journal of Gastroenterology Volume: -
  • DOI: 10.1007/s00535-020-01679-7
  • Peer Reviewed / Open Access
• [Journal Article] Xanthine oxidase inhibition attenuates insulin resistance and diet-induced steatohepatitis in mice (2020)
  • Author(s): Nishikawa Tomoki、Nagata Naoto、Shimakami Tetsuro、Shirakura Takashi、Matsui Chieko、Ni Yinhua、Zhuge Fen、Xu Liang、Chen Guanliang、Nagashimada Mayumi、Yamashita Taro、Sakai Yoshio、Yamashita Tatsuya、Mizukoshi Eishiro、Honda Masao、Kaneko Shuichi、Ota Tsuguhito
  • Journal Title: Sci Rep Volume: 10 Pages: 815-815
  • DOI: 10.1038/s41598-020-57784-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Gut-derived Enterococcus faecium from ulcerative colitis patients promotes colitis in a genetically susceptible mouse host (2019)
  • Author(s): Seishima Jun、Iida Noriho、Kitamura Kazuya、Yutani Masahiro、Wang Ziyu、Seki Akihiro、Yamashita Taro、Sakai Yoshio、Honda Masao、Yamashita Tatsuya、Kagaya Takashi、Shirota Yukihiro、Fujinaga Yukako、Mizukoshi Eishiro、Kaneko Shuichi
  • Journal Title: Genome Biology Volume: 20 Pages: 1-18
  • DOI: 10.1186/s13059-019-1879-9
  • Peer Reviewed / Open Access
• [Journal Article] Danaparoid sodium-based anticoagulation therapy for portal vein thrombosis in cirrhosis patients (2019)
  • Author(s): Hayashi T、Takatori H、Horii R、Nio K、Terashima T、Iida N、Kitahara M、Shimakami T、Arai K、Kitamura K、Kawaguchi K、Yamashita T、Sakai Y、Yamashita T、Mizukoshi E、Honda M、Toyama T、Okumura K、Kozaka K、Kaneko S
  • Journal Title: BMC gastroenterology Volume: 19 Pages: 217-217
  • DOI: 10.1186/s12876-019-1140-8
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA‐10a Impairs Liver Metabolism in Hepatitis C Virus‐Related Cirrhosis Through Deregulation of the Circadian Clock Gene Brain and Muscle Aryl Hydrocarbon Receptor Nuclear Translocator‐Like 1 (2019)
  • Author(s): Horii Rika、Honda Masao、Shirasaki Takayoshi、Shimakami Tetsuro、Shimizu Ryogo、Yamanaka Souma、Murai Kazuhisa、Kawaguchi Kazunori、Arai Kuniaki、Yamashita Tatsuya、Sakai Yoshio、Yamashita Taro、Okada Hikari、Nakamura Mikiko、Mizukoshi Eishiro、Kaneko Shuichi
  • Journal Title: Hepatology Communications Volume: 3 Pages: 1687-1703
  • DOI: 10.1002/hep4.1431
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: Hepatology. Volume: 10.1002/hep Pages: 30637-30637
  • DOI: 10.1002/hep.30637
  • Peer Reviewed / Open Access
• [Journal Article] Establishment and Characterization of a New Cell Line Permissive for Hepatitis C Virus Infection (2019)
  • Author(s): Omura Hitoshi、Liu Fanwei、Shimakami Tetsuro、Murai Kazuhisa、Shirasaki Takayoshi、Kitabayashi Juria、Funaki Masaya、Nishikawa Tomoki、Nakai Ryotaro、Sumiyadorj Ariunaa、Hayashi Takehiro、Yamashita Taro、Honda Masao、Kaneko Shuichi
  • Journal Title: Scientific Reports Volume: 9 Pages: 7943-7943
  • DOI: 10.1038/s41598-019-44257-5
  • Peer Reviewed / Open Access
• [Journal Article] Biological characteristics of gene expression features in pancreatic cancer cells induced by proton and X-ray irradiation. (2019)
  • 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.
  • Journal Title: International journal of radiation biology Volume: 17 Pages: 571-579
  • DOI: 10.1080/09553002.2019.1558297
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: Cell Host Microbe. Volume: 10;25(4) Pages: 588-301
  • DOI: 10.1016/j.chom.2019.02.015
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: 34 Pages: 1829-1835
  • DOI: 10.1111/jgh.14654
  • Peer Reviewed / Open Access
• [Journal Article] Adipose tissue‐derived stem cells prevent fibrosis in murine steatohepatitis by suppressing IL‐17‐mediated inflammation (2019)
  • Author(s): Yamato Masatoshi、Sakai Yoshio、Mochida Hatsune、Kawaguchi Kazunori、Takamura Masayuki、Usui Soichiro、Seki Akihiro、Mizukoshi Eishiro、Yamashita Taro、Yamashita Tatsuya、Ishida Kousuke、Nasti Alessandro、Tuyen Ho Thuy Bich、Komura Takuya、Yoshida Keiko、Wada Takashi、Honda Masao、Kaneko Shuichi
  • Journal Title: J Gastroenterol Hepatol Volume: - Pages: 1432-1440
  • DOI: 10.1111/jgh.14647
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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.
  • Journal Title: Cancer Sci. Volume: 110 Pages: 903-912
  • DOI: 10.1111/cas.13944
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Surrogacy of Time to Progression for Overall Survival in Advanced Hepatocellular Carcinoma Treated with Systemic Therapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (2019)
  • Author(s): Terashima Takeshi、Yamashita Tatsuya、Toyama Tadashi、Arai Kuniaki、Kawaguchi Kazunori、Kitamura Kazuya、Yamashita Taro、Sakai Yoshio、Mizukoshi Eishiro、Honda Masao、Kaneko Shuichi
  • Journal Title: Liver Cancer. Volume: 8 Pages: 130-139
  • DOI: 10.1159/000489505
  • Peer Reviewed / Open Access
• [Journal Article] Development of novel diagnostic system for pancreatic cancer, including early stages, measuring mRNA of whole blood cells (2019)
  • Author(s): Sakai Yoshio、Honda Masao、Matsui Shigeyuki、Komori Osamu、Murayama Toshinori、Fujiwara Tadami、Mizuno Masaaki、Imai Yasuhito、Yoshimura Kenichi、Nasti Alessandro、Wada Takashi、Iida Noriho、Kitahara Masaaki、Horii Rika、Toshikatsu Tamai、Nishikawa Masashi、Okafuji Hirofumi、Mizukoshi Eishiro、et al
  • Journal Title: Cancer Sci. Volume: 110 Pages: 1364-1388
  • DOI: 10.1111/cas.13971
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: Clin J Gastroenterol. Volume: 12 Pages: 63-70
  • DOI: 10.1007/s12328-018-0884-y
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: Hepatology Volume: 69 Pages: 653-665
  • DOI: 10.1002/hep.30212
  • Peer Reviewed / Open Access
• [Journal Article] POGLUT1, the putative effector gene driven by rs2293370 in primary biliary cholangitis susceptibility locus chromosome 3q13.33 (2019)
  • Author(s): Hitomi, Y. Ueno, K. Kawai, Y. Nishida, N. , Umemura, T. et al
  • Journal Title: Sci Rep. Volume: 9 Pages: 102-102
  • DOI: 10.1038/s41598-018-36490-1
  • NAID: 120006715480
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: J Gastroenterol. Volume: - Pages: 549-557
  • DOI: 10.1007/s00535-019-01551-3
  • Peer Reviewed / Open Access
• [Journal Article] Notch signaling facilitates hepatitis B virus covalently closed circular DNA transcription via cAMP response element-binding protein with E3 ubiquitin ligase-modulation (2019)
  • Author(s): Wang Zijing、Kawaguchi Kazunori、Honda Masao、Hashimoto Shinichi、Shirasaki Takayoshi、Okada Hikari、Orita Noriaki、Shimakami Tetsuro、Yamashita Taro、Sakai Yoshio、Mizukoshi Eishiro、Murakami Seishi、Kaneko Shuichi
  • Journal Title: Sci Rep Volume: 9 Pages: 1621-1621
  • DOI: 10.1038/s41598-018-38139-5
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: Hepatology Research Volume: 48 Pages: 956-966
  • DOI: 10.1111/hepr.13196
  • Peer Reviewed / Open Access
• [Journal Article] Immune responses against tumor-associated antigen-derived cytotoxic T lymphocyte epitopes in cholangiocarcinoma patients. (2018)
  • Author(s): Kida A, Mizukoshi E, Tamai T, Kitahara M, Yamashita T, Arai K, Terashima T, Iida N, Fushimi K, Kaneko S.
  • Journal Title: Liver International Volume: 38 Pages: 2040-2050
  • DOI: 10.1111/liv.13885
  • Peer Reviewed / Open Access
• [Journal Article] Prevention of hepatocellular carcinoma by targeting MYCN-positive liver cancer stem cells with acyclic retinoid (2018)
  • 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
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 115 Pages: 4969-4974
  • DOI: 10.1073/pnas.1802279115
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genome-wide association study identified new susceptible genetic variants in HLA class I region for hepatitis B virus-related hepatocellular carcinoma (2018)
  • 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
  • Journal Title: Scientific Reports Volume: 8 Pages: 7958-7958
  • DOI: 10.1038/s41598-018-26217-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Unexpected Replication Boost by Simeprevir for Simeprevir-resistant Variants in Genotype 1a Hepatitis C Virus (2018)
  • 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.
  • Journal Title: Antimicrobial Agents and Chemotherapy Volume: 印刷中
  • DOI: 10.1128/aac.02601-17
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Distinct notch signaling expression patterns between nucleoside and nucleotide analogues treatment for hepatitis B virus infection. (2018)
  • Author(s): Wang Z, Kawaguchi K, Honda M, Sakai Y, Yamashita T, Mizukoshi E, Kaneko S.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 501 Pages: 682-687
  • DOI: 10.1016/j.bbrc.2018.04.236
  • Peer Reviewed / Open Access
• [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. (2018)
  • 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
  • Journal Title: Journal of Gastroenterology Volume: ePub ahead Pages: 740-751
  • DOI: 10.1007/s00535-017-1386-2
  • Peer Reviewed / Open Access
• [Journal Article] Immune responses of human T lymphocytes to novel hepatitis B virus-derived peptides (2018)
  • Author(s): Yamamiya D, Mizukoshi E, Kaji K, Terashima T, Kitahara M, Yamashita T, Arai K, Fushimi K, Honda M, Kaneko S.
  • Journal Title: PLOS ONE Volume: 13
  • DOI: 10.1371/journal.pone.0198264
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: Canadian Journal of Gastroenterology and Hepatology Volume: 7436205 Pages: 7436205-7436205
  • DOI: 10.1155/2018/7436205
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: Scientific Reports Volume: 8 Pages: 13143-13143
  • DOI: 10.1038/s41598-018-31421-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] NASHにおける新規バイオマーカーとしての血清ＡＫＲ1Ｂ10の有用性 (2019)
  • Author(s): 神野正隆，本多政夫，金子周一
  • Organizer: 第105回日本消化器病学会総会
• [Presentation] 肝線維化に伴うリモデリングを正常化する新規治療法の開発 (2019)
  • Author(s): 岡田光、本多政夫、金子周一
  • Organizer: 第55回日本肝臓学会総会
• [Presentation] ヒト非B非C肝癌におけるシングルセル遺伝子発現解析 (2019)
  • Author(s): 岩淵 禎弘、川口 和紀、本多 政夫、山下 太郎、山下 竜也、金子 周一、橋本 真一
  • Organizer: 第78回日本癌学会学術学会総会
• [Presentation] Heterogeneity of tumor micro-environment in 2 different HBV associated HCCs (2019)
  • Author(s): Sadahiro Iwabuchi, Kazunori Kawaguchi, Masao Honda, Tarp Yamashita, Tatsuya Yamashita, Shuichi Kaneko
  • Organizer: International HBV meeting 2019
  • Int'l Joint Research
• [Presentation] Serum aldo-keto reductase family 1 member B10 predicts HBV-related hepatocellular carcinoma during nucleos(t)ide analogue treatment (2019)
  • 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
  • Int'l Joint Research
• [Presentation] Identification of a host factor for the improvement of immune checkpoint blockade therapy for hepatocellular carcinoma (2019)
  • Author(s): Kazuhisa Murai, Masao Honda, Takayoshi Shirasaki, Seishi Murakami, and Shuichi Kaneko
  • Organizer: AASLD2019
  • Int'l Joint Research
• [Presentation] Genome-wide methylation analysis identified a new intrahepatic vascular endothelial marker associated with induction of tumorigenesis after successful eradication of HCV (2019)
  • Author(s): Masashi Nishikawa, Masao Honda, Shuichi Kaneko
  • Organizer: AASLD2019
  • Int'l Joint Research
• [Presentation] NASH患者における肝線維化と血清AKR1B10との関連 (2018)
  • Author(s): 川口和紀，神野正隆，本多政夫，金子周一
  • Organizer: 第104回日本消化器病学会総会
• [Presentation] ペレチノインの作用機序からみた肝癌化学予防療法の個別化医療の可能性 (2018)
  • Author(s): 山下太郎，本多政夫，金子周一
  • Organizer: 第104回日本消化器病学会総会
• [Presentation] 肝癌治療後C型慢性肝疾患に対する抗ウイルス薬治療後の肝癌再発に関する検討 (2018)
  • Author(s): 舩木雅也，島上哲朗，堀井里和，砂子阪肇，荒井邦明，山下太郎，酒井佳夫，山下竜也，水腰英四郎，本多政夫，金子周一
  • Organizer: 第104回日本消化器病学会総会
• [Presentation] HBV cccDNAに作用する転写因子を標的とした抗HBV効果 (2018)
  • Author(s): 川口和紀，本多政夫，金子周一
  • Organizer: 第104回日本消化器病学会総会
• [Presentation] 難治性腹水を伴う非代償性肝硬変におけるトルバプタン導入後の肝癌治療と予後について (2018)
  • Author(s): 朝日向良朗，堀井里和，丹尾幸樹，飯田宗穂，北原征明，寺島健志，鷹取元，荒井邦明，川口和紀，北村和哉，山下太郎，酒井佳夫，山下竜也、水腰英四郎，本多政夫，金子周一
  • Organizer: 第54回日本肝臓学科総会
• [Presentation] HBV生活環におけるNotchシグナルを介した核酸アナログの作用点に関する検討 (2018)
  • Author(s): 川口和紀，本多政夫，金子周一
  • Organizer: 第54回日本肝臓学科総会
• [Presentation] C型慢性肝疾患に対する第2世代DAAの治療成績とDAA非著効例に対する再治療成績に関する解析 (2018)
  • Author(s): 島上哲朗，本多政夫，金子周一
  • Organizer: 第54回日本肝臓学科総会
• [Presentation] 当科における抗ミトコンドリア抗体陰性原発性胆汁性胆管炎の検討 (2018)
  • Author(s): 岡藤啓史，北村和哉，朝日向良朗，高田昇，堀井里和，北原征明，飯田宗穂，鷹取 元，島上哲朗，荒井邦明，川口和紀，山下太郎，酒井佳夫，山下竜也，水腰英四郎，本多政夫，金子周一
  • Organizer: 第54回日本肝臓学科総会
• [Presentation] B型慢性肝炎患者の核酸アナログ投与下における肝線維化と肝発癌および再発予測 (2018)
  • Author(s): 川口和紀，本多政夫，金子周一
  • Organizer: JDDW2018
• [Presentation] NASHにおける血清バイオマーカーを組み合わせた肝発癌および重症度予測 (2018)
  • Author(s): 神野正隆，川口和紀，本多政夫，金子周一
  • Organizer: JDDW2018
• [Presentation] Characteristics and Functional Regulation of Dendritic Cells in Hepatitis B Patients (2018)
  • 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
  • Int'l Joint Research
• [Presentation] Mint3 is a novel molecular target expressed in well-differentiated AFP-negative HCC for prevention of cancer progression (2018)
  • Author(s): Nishitani Masaki, Yamashita Taro, Okada Hikari, Nio Kouki, Suda Tsuyoshi, Takatori Hajime, Honda Masao, Sakamoto Takeharu, Kaneko Shuichi
  • Organizer: AASLD2018
  • Int'l Joint Research
• [Presentation] A Liver-Derived Secretory Protein, LECT2, Enhances the Innate Immune Response and Suppresses RIG-I Mediated Virus Infection (2018)
  • Author(s): Takayoshi Shirasaki, Masao Honda, Kazuhisa Murai, Tetsuro Shimakami, Hirofumi Misu, Toshinari Takamura, Shuichi Kaneko
  • Organizer: AASLD2018
  • Int'l Joint Research
• [Presentation] Levocarnitine improves Liver Histology and the Development of Hepatocellular Carcinoma in the Atherogenic High-Fat Diet Nash-HCC Mouse Model (2018)
  • Author(s): Hikari Okada, Masao Honda, Hajime Sunakozaka, Shuichi Kaneko
  • Organizer: AASLD2018
  • Int'l Joint Research
• [Presentation] Adipose tissue derived stromal/stem cells alleviated hepatic fibrosis development induced by IL17-mediated stellate cell activation in NASH mice (2018)
  • Author(s): Masatoshi Yamato, Yoshio Sakai, Hatsune Mochida, Takuya Komura, Alessandro Nasti, Akihiro Seki, Kazunori Kawaguchi, Takashi Wada, Masao Honda, Shuichi Kaneko
  • Organizer: AASLD2018
  • Int'l Joint Research
• [Presentation] Immune response to tumor-associated antigens and immune vell profiles in NASH-related hepatocellular carcinoma (2018)
  • 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
  • Int'l Joint Research
• [Presentation] Inactivation of transcriptional repressor capicua confers chemoresistance to sorafenib in hepatocellular carcinoma (2018)
  • Author(s): Tomomi Hashiba, Taro Yamashita, Hikari Okada, Kouki Nio, Takehiro Hayashi, Masao Honda, Shuichi Kaneko
  • Organizer: AASLD2018
  • Int'l Joint Research
• [Presentation] Elevation of serum aldo-keto reductase family 1 member B10 is associated with advanced liver fibrosis in non-alcoholic steatohepatitis (2018)
  • 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
  • Int'l Joint Research