Investigation of tumor immune escape mechanisms in liver cancer using allograft mouse model

• Project/Area Number: 20K08276
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Chiba University
• Principal Investigator: Chiba Tetsuhiro 千葉大学, 大学院医学研究院, 講師 (00381583)
• Co-Investigator(Kenkyū-buntansha): 金山 健剛 千葉大学, 医学部附属病院, 医員 (20835102)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 腫瘍微小環境 / 癌免疫逃避機構 / 免疫チェックポイント / 肝細胞癌

Outline of Research at the Start

免疫チェックポイント阻害分子を介した腫瘍細胞と免疫担当細胞の相互作用は癌免疫回避機
構として機能し、「薬物治療による癌の根治」を困難なものとする。近年、消化器癌領域に
おいても免疫チェックポイント阻害薬の承認・開発が進んでいるが、こうした薬剤の単独使用では治療効果が不十分であることが多く、更なる治療アプローチの創意工夫が必要である。本研究では、まずマウスモデルを用いて多様な切り口から肝細胞癌の癌免疫微小環境の詳細な解析を行うことにより、癌免疫逃避メカニズムの解明と新規治療アプローチの創出を試みる。

Outline of Final Research Achievements

The antitumor effect of UNC1999, an EZH2 inhibitor, was clearly attenuated in an allogeneic mouse model compared to an immunodeficient mouse model. Flow cytometric analysis of H22 cell-derived tumors in BALB/c mice showed a significant decrease in interferon gamma+ CD8+ T cells and regulatory T cells and a significant increase in myeloid-derived suppressor cells (MDSCs). Combination of UNC1999 with Gr-1 neutralizing antibody restored the antitumor effect with an increase in the number of CD8+ T cells and a decrease in the number of MDSCs.
In conclusion, EZH2 inhibition contributes to attenuation of tumor immunity, and combination therapy with EZH2 inhibitors and agents that reduce MDSCs may be a novel therapeutic strategy for hepatocellular carcinoma.

Academic Significance and Societal Importance of the Research Achievements

ポリコームタンパクEZH2は肝細胞がんにおいて高発現しており、発癌並びに癌の進行に大きな役割を果たすことが知られている。本研究では、同種移植マウスモデルにEZH2阻害剤を投与することで、EZH2の肝癌微小環境に与える影響を詳細に検証する事ができた。本研究成果は、癌免疫療法の新規アプローチの分子基盤の提供を可能とするものであり、学術的意義も富むものと考えられる。

Research Products

• [Journal Article] Miglustat, a glucosylceramide synthase inhibitor, mitigates liver fibrosis through TGF-β/Smad pathway suppression in hepatic stellate cells (2023)
  • Author(s): Iwanaga T, Chiba T, Nakamura M, et al.
  • Journal Title: Biochem Biophys Res Commun Volume: 642 Pages: 192-200
  • DOI: 10.1016/j.bbrc.2022.12.025
  • Peer Reviewed
• [Journal Article] Successful Identification of a Novel Therapeutic Compound for Hepatocellular Carcinoma Through Screening of ADAM9 Inhibitors. (2023)
  • Author(s): Ogawa K, Chiba T, Nakamura M, Arai J, Zhang J, et al.
  • Journal Title: Anticancer Res. Volume: 43 Issue: 3 Pages: 1043-1052
  • DOI: 10.21873/anticanres.16249
  • Peer Reviewed / Open Access
• [Journal Article] Alteration of the tumor microenvironment by pharmacological inhibition of EZH2 in hepatocellular carcinoma. (2023)
  • Author(s): Qiang N, Ao J, Nakamura M, Chiba T, Kusakabe Y, Kaneko T, Kurosugi A, Kogure T, Ma Y, Zhang J, Ogawa K, Kan M, Iwanaga T, Sakuma T, Kanayama K, Kanzaki H, Kojima R, Nakagawa R, Kondo T, Nakamoto S, Muroyama R, Kato J, Mimura N, Ma A, Jin J, Kato N.
  • Journal Title: Int Immunopharmacol. Volume: 118 Pages: 110068-110068
  • DOI: 10.1016/j.intimp.2023.110068
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effect of Atezolizumab plus Bevacizumab in Patients with Hepatocellular Carcinoma Harboring CTNNB1 Mutation in Early Clinical Experience. (2022)
  • Author(s): Ogawa K, Kanzaki H, Chiba T, Ao J, Qiang N, et al.
  • Journal Title: J Cancer Volume: 13 Issue: 8 Pages: 2656-2661
  • DOI: 10.7150/jca.71494
  • Peer Reviewed / Open Access
• [Journal Article] The RNA-Binding Protein ELAVL1 Regulates Hepatitis B Virus Replication and Growth of Hepatocellular Carcinoma Cells. (2022)
  • Author(s): Kanzaki H, Chiba T, Kaneko T, Ao J, Kan M, Muroyama R, Nakamoto S, Kanda T, Maruyama H, Kato J, Zen Y, Kotani A, Sekiba K, Otsuka M, Ohtsuka M, Kato N.
  • Journal Title: Int J Mol Sci Volume: 23 Issue: 14 Pages: 7878-7878
  • DOI: 10.3390/ijms23147878
  • Peer Reviewed / Open Access
• [Journal Article] A diet-induced murine model for non-alcoholic fatty liver disease with obesity and insulin resistance that rapidly develops steatohepatitis and fibrosis. (2022)
  • Author(s): Sakuma T, Nakamura M, Chiba T, Iwanaga T, Kan M, Kojima R, Ao J, Ma Y, Unozawa H, Fujita N, Kanayama K, Kanzaki H, Koroki K, Kobayashi K, Nakagawa R, Kanogawa N, Kiyono S, Kondo T, Saito T, Ogasawara S, Nakamoto S, Muroyama R, Kato J, Kishimoto T, Kato N.
  • Journal Title: Lab Invest. Volume: 102 Issue: 10 Pages: 1150-1157
  • DOI: 10.1038/s41374-022-00807-6
  • Peer Reviewed
• [Journal Article] Bile proteome analysis by high-precision mass spectrometry to examine novel biomarkers of primary sclerosing cholangitis. (2022)
  • Author(s): Kan M, Chiba T, Konno R, Kouchi Y, Mishima T, Kawashima Y, Kishimoto T, Ohtsuka M, Ohara O, Kato N.
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: in press Issue: 7 Pages: 914-923
  • DOI: 10.1002/jhbp.1299
  • Peer Reviewed
• [Journal Article] EZH1/2 inhibition augments the anti-tumor effects of sorafenib in hepatocellular carcinoma (2021)
  • Author(s): Kusakabe Y, Chiba T, Zen Y, Otsuka M, Kaneda A, Iwama A, Kato N, et al
  • Journal Title: Sci Rep Volume: 11 Issue: 1 Pages: 21396-21396
  • DOI: 10.1038/s41598-021-00889-0
  • Peer Reviewed / Open Access
• [Journal Article] Human hepatocyte-derived extracellular vesicles attenuate the carbon tetrachloride-induced acute liver injury in mice (2021)
  • Author(s): Kakizaki Masatoshi、Yamamoto Yuichiro、Nakayama Shunya、Kameda Kazuaki、Nagashima Etsuko、Ito Masatoshi、Suyama Takashi、Matsuzaki Yumi、Chiba Tetsuhiro、Sumiyoshi Hideaki、Inagaki Yutaka、Kotani Ai
  • Journal Title: Cell Death and Disease Volume: 12 Issue: 11 Pages: 1010-1010
  • DOI: 10.1038/s41419-021-04204-7
  • Peer Reviewed / Open Access
• [Journal Article] Genetic profiles of Barrett’s esophagus and esophageal adenocarcinoma in Japanese patients (2021)
  • Author(s): Tokunaga Mamoru、Okimoto Kenichiro、Akizue Naoki、Ishikawa Kentaro、Hirotsu Yosuke、Amemiya Kenji、Ota Masayuki、Matsusaka Keisuke、et al.
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 17671-17671
  • DOI: 10.1038/s41598-021-97249-9
  • Peer Reviewed / Open Access
• [Journal Article] Diagnostic value of IMP3 and p53 immunohistochemical staining in EUS-guided fine-needle aspiration for solid pancreatic tumors (2021)
  • Author(s): Mikata R, Yasui S, Kishimoto T, Kouchi Y, Shingyoji A, Senoo J, Takahashi K, Nagashima H, Kusakabe Y, Ohyama H, Ohno I, Sugiyama H, Chiba T, Kato J, Kato N.
  • Journal Title: Sci Rep. Volume: 11 Issue: 1 Pages: 17257-17257
  • DOI: 10.1038/s41598-021-96492-4
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive mutational analysis of background mucosa in patients with Lugol‐voiding lesions (2021)
  • Author(s): Akizue Naoki、Okimoto Kenichiro、Arai Makoto、Hirotsu Yosuke、Amemiya Kenji、Oura Hirotaka、Kaneko Tatsuya et al
  • Journal Title: Cancer Medicine Volume: 10 Issue: 11 Pages: 3545-3555
  • DOI: 10.1002/cam4.3905
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of circulating cell-free DNA after endoscopic ultrasound-guided fine needle aspiration in pancreatic ductal adenocarcinoma. (2021)
  • Author(s): Asano K, Mikata R, Chiba T, Kan M, Maruta S, Yamada T, Miura Y, Shima Y, Sensui M, Nagashima H, Yokoyama M, Ohyama H, Kusakabe Y, Yasui S, Sugiyama H, Ohno I, Kato J, Takano S, Ohtsuka M, Kato N.
  • Journal Title: Pancreatology Volume: - Issue: 6 Pages: 3903-3903
  • DOI: 10.1016/j.pan.2021.04.001
  • Peer Reviewed
• [Journal Article] Serum Angiopoietin 2 acts as a diagnostic and prognostic biomarker in hepatocellular carcinoma (2021)
  • Author(s): Ao Junjie、Tawada Akinobu、Kato Naoya et al
  • Journal Title: Journal of Cancer Volume: 12 Issue: 9 Pages: 2694-2701
  • DOI: 10.7150/jca.56436
  • Peer Reviewed / Open Access
• [Journal Article] Acquisition of mesenchymal-like phenotypes and overproduction of angiogenic factors in lenvatinib-resistant hepatocellular carcinoma cells (2021)
  • Author(s): Ao J, Chiba T, Shibata S, Kurosugi A, Qiang N, Ma Y, Kan M, Iwanaga T, Sakuma T, Kanzaki H, Kanayama K, Kojima R, Kusakabe Y, Nakamura M, Saito T, Nakagawa R, Kondo T, Ogasawara S, Suzuki E, Muroyama R, Kato J, Mimura N, Kanda T, Maruyama H, Kato N.
  • Journal Title: Biochem Biophys Res Commun. Volume: 549 Pages: 171-178
  • DOI: 10.1016/j.bbrc.2021.02.097
  • Peer Reviewed
• [Journal Article] The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma (2021)
  • Author(s): Kanzaki H、Chiba T、Ao J、Koroki K、Kanayama K、Maruta S、Maeda T、Kusakabe Y、Kobayashi K、Kanogawa N、Kiyono S、Nakamura M、Kondo T、Saito T、Nakagawa R、Ogasawara S、Suzuki E、Ooka Y、Muroyama R、Nakamoto S、Yasui S、Tawada A、Arai M、Kanda T、Maruyama H、Mimura N、Kato J、Zen Y、Ohtsuka M、Iwama A、Kato N
  • Journal Title: Sci Rep Volume: 11 Issue: 1 Pages: 5303-5303
  • DOI: 10.1038/s41598-021-84117-9
  • Peer Reviewed / Open Access
• [Journal Article] The combination of the tubulin binding small molecule PTC596 and proteasome inhibitors suppresses the growth of myeloma cells. (2021)
  • Author(s): Nagai Y, Mimura N, Nakaseko C et al
  • Journal Title: Sci Rep Volume: 11 Issue: 1 Pages: 2074-2074
  • DOI: 10.1038/s41598-021-81577-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The efficacy of linked color imaging in the endoscopic diagnosis of Barrett’s esophagus and esophageal adenocarcinoma. (2020)
  • Author(s): Tokunaga M, Matsumura T, Ishikawa K, Kaneko T, Oura H, Ishikawa T, Nagashima A, Shiratori W, Okimoto K, Akizue N, Maruoka D, Ohta Y, Saito K, Nakagawa T, Chiba T, Arai M, Kato J, Kato N.
  • Journal Title: Gastroenterol Res Pract Volume: 2020 Pages: 9604345-9604345
  • DOI: 10.1155/2020/9604345
  • Peer Reviewed / Open Access
• [Journal Article] Analyses of intermediate-stage hepatocellular carcinoma patients receiving TACE prior to designing clinical trials. (2020)
  • Author(s): Koroki K, Ogasawara S, Ooka Y, Kanzaki H, Kanayama K, Maruta S, Maeda T, Yokoyama M, Wakamatsu T, Inoue M, Kobayashi K, Kiyono S, Nakamura M, Kanogawa N, Saito T, Kondo T, Suzuki E, Nakamoto S, Yasui S, Tawada A, Chiba T, Arai M, Kanda T, Maruyama H, Kato J, Kuboki S, Ohtsuka Miyazaki M, Yokosuka O, Kato N.
  • Journal Title: Liver Cancer Volume: 9 Issue: 5 Pages: 596-612
  • DOI: 10.1159/000508809
  • Peer Reviewed / Open Access
• [Journal Article] A randomized, double-blind, placebo-controlled, phase 3 study of tivantinib in Japanese patients with MET-high hepatocellular carcinoma. (2020)
  • Author(s): Kudo M, Morimoto M, Moriguchi M, Izumi N, Takayama T, Yoshiji H, Hino K, Oikawa T, Chiba T, Motomura K, Kato J, Yasuchika K, Ido A, Sato T, Nakashima D, Ueshima K, Ikeda M, Okusaka T, Tamura K, Furuse J.
  • Journal Title: Cancer Sci Volume: 111 Issue: 10 Pages: 3759-3769
  • DOI: 10.1111/cas.14582
  • Peer Reviewed / Open Access
• [Journal Article] Interferon-γ induced PD-L1 expression and soluble PD-L1 production in gastric cancer. (2020)
  • Author(s): Imai Y, Chiba T, Kondo T, Kanzaki H, Kanayama K, Ao J, Kojima R, Kusakabe Y, Nakamura M, Saito T, Nakagawa R, Suzuki E, Nakamoto S, Muroyama R, Tawada A, Matsumura T, Nakagawa T, Kato J, Kotani A, Matsubara H, Kato N.
  • Journal Title: Oncol Lett Volume: 20 Issue: 3 Pages: 2161-2168
  • DOI: 10.3892/ol.2020.11757
  • Peer Reviewed
• [Journal Article] PD-L1 is induced on hepatocyte surface via CKLF-like MARVEL transmembrane domain-containing protein 6 upregulation by the anti-HBV drug Entecavir (2020)
  • Author(s): Yamamoto Yuichiro、Kakizaki Masatoshi、Shimizu Takayuki、Carreras Joaquim、Chiba Tetsuhiro、Chamoto Kenji、Kagawa Tatehiro、Aoki Taku、Nakamura Naoya、Ando Kiyoshi、Kotani Ai
  • Journal Title: International Immunology Volume: - Issue: 8 Pages: 519-531
  • DOI: 10.1093/intimm/dxaa018
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Long-term administration of Tolvaptan to patients with decompensated cirrhosis. (2020)
  • Author(s): Kanayama K, Chiba T, Kobayashi K, Koroki K, Maruta S, Kanzaki H, Kusakabe Y, Saito T, Kiyono S, Nakamura M, Ogasawara S, Suzuki E, Ooka H, Yasui S, Nakamoto S, Kanda T, Maruyama H, Kato J, Kato N.
  • Journal Title: Int J Med Sci Volume: 17 Issue: 7 Pages: 874-880
  • DOI: 10.7150/ijms.41454
  • Peer Reviewed / Open Access
• [Journal Article] Sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Japan. (2020)
  • Author(s): Ogasawara S, Ooka Y, Itokawa N, Inoue M, Okabe S, Obu M, Atsukawa M, Itobayashi E, Mizumoto H, Sugiura N, Azemoto R, Kanayama K, Kanzaki H, Maruta S, Maeda T, Kusakabe Y, Yokoyama M, Kobayashi K, Kiyono S, Nakamura M, Saito T, Suzuki E, Nakamoto S, Yasui S, Tawada A, Chiba T, Arai M, Kanda T, Maruyama H, Kato N
  • Journal Title: Invest New Drugs Volume: 38 Issue: 1 Pages: 172-180
  • DOI: 10.1007/s10637-019-00801-8
  • Peer Reviewed
• [Journal Article] Potential of Lenvatinib for an Expanded Indication from the REFLECT Trial in Patients with Advanced Hepatocellular Carcinoma. (2020)
  • Author(s): Maruta S, Ogasawara S, Ooka Y, Obu M, Inoue M, Itokawa N, Haga Y, Seki A, Okabe S, Azemoto R, Itobayashi E, Atsukawa M, Sugiura N, Mizumoto H, Koroki K, Kanayama K, Kanzaki H, Kobayashi K, Kiyono S, Nakamura M, Kanogawa N, Saito T, Kondo T, Suzuki E, Nakamoto S, Tawada A, Chiba T, Arai M, Kanda T, Maruyama H, Kato N.
  • Journal Title: Liver Cancer Volume: 9 Issue: 4 Pages: 382-396
  • DOI: 10.1159/000507022
  • Peer Reviewed / Open Access
• [Journal Article] Free fatty acid-based low-impedance liver image: a characteristic appearance in nonalcoholic steatohepatitis (NASH). (2020)
  • Author(s): Maruyama H, Kobayashi K, Kiyono S, Chiba T, Kato N, Ohtsuka M, Ito K, Yamaguchi T, Shiina S.
  • Journal Title: Eur Radiol Exp Volume: 4 Issue: 1 Pages: 3-3
  • DOI: 10.1186/s41747-019-0137-y
  • Peer Reviewed / Open Access
• [Presentation] 高精度質量分析を用いた胆汁プロテオーム解析による原発性硬化性胆管炎の病態解明の 試み (2022)
  • Author(s): 菅元康、千葉哲博、加藤直也
  • Organizer: 第108回日本消化器病学会総会
• [Presentation] 肝細胞癌におけるCTNNB1遺伝子変異とアテゾリズマブ/ベバシズマブ併用療法の初期治療効果と末梢血CCL5濃度に関する検討 (2022)
  • Author(s): 小川慶太、千葉哲博、加藤直也
  • Organizer: 第59回日本消化器免疫学会総会
• [Presentation] Role of FGF19/FGFR4 Signaling and Potential of Serum FGF19 as a Biomarker in Hepatocellular Carcinoma. (2021)
  • Author(s): Chiba T
  • Organizer: APASL Oncology 2021
  • Int'l Joint Research
• [Presentation] Impacts of EZH2 inhibitor UNC1999 on tumor and tumor microenvironment in hepatocellular carcinoma (2021)
  • Author(s): Ao J, Chiba T, Kaneko T et al.
  • Organizer: APASL Oncology 2021
  • Int'l Joint Research
• [Presentation] The effect of glucosylceramide synthase inhibitor on liver fibrosis regression (2021)
  • Author(s): Iwanaga T, Chiba T, Zhang J, et al.
  • Organizer: APASL Oncology 2021
  • Int'l Joint Research
• [Presentation] Effects of EZH2 inhibition on tumor and tumor microenvironment in hepatocellular carcinoma (2021)
  • Author(s): Ao J, Chiba T, Kato N.
  • Organizer: AASLD The Liver Meeting 2021
  • Int'l Joint Research
• [Presentation] Involvement of FGF and VEGF signaling in multi-kinase inhibitor resistance in hepatocellular carcinoma (2021)
  • Author(s): Kanzaki H, Chiba T, Kato N.
  • Organizer: AASLD The Liver Meeting 2021
  • Int'l Joint Research
• [Presentation] EZH2阻害剤の肝癌微小環境に与える影響の検討 (2021)
  • Author(s): 敖俊杰, 千葉哲博, 加藤直也
  • Organizer: JDDW 2021
• [Presentation] 血清Angiopoietin 2の肝細胞癌新規バイオマーカーとしての有用性 (2021)
  • Author(s): 強娜, 千葉哲博, 敖俊杰, 他.
  • Organizer: JDDW 2021
• [Presentation] 血清可溶型PD-L1のバイオマーカーとしての意義-アテゾリズマブ/ベバシズマブ併用症例を含めて- (2021)
  • Author(s): 神﨑洋彰, 千葉哲博, 加藤直也
  • Organizer: 第57回日本肝癌研究会
• [Presentation] 血清FGF19値に基づいた肝細胞癌に対するレンバチニブの後方治療時の成績 (2021)
  • Author(s): 千葉哲博, 神﨑洋彰, 敖俊杰, 他.
  • Organizer: 第57回日本肝癌研究会
• [Presentation] 肝細胞癌におけるGas6と可溶型Axlのバイオマーカーとしての有用性の検証 (2021)
  • Author(s): 佐久間崇文, 千葉哲博, 加藤直也
  • Organizer: 第57回 日本肝臓学会総会
• [Presentation] グルコシルセラミド合成酵素阻害薬の肝線維化抑制効果の検討 (2021)
  • Author(s): 岩永光巨, 千葉哲博, 加藤直也
  • Organizer: 第57回 日本肝臓学会総会
• [Presentation] マルチキナーゼ阻害剤耐性化におけるFGFシグナルとVEGFシグナルの関わり (2021)
  • Author(s): 神﨑洋彰, 千葉哲博, 加藤直也
  • Organizer: 第107回 日本消化器病学会総会
• [Presentation] 新規食餌誘導性非アルコール性脂肪性肝疾患マウスモデルの構築と病態解析 (2021)
  • Author(s): 中村昌人, 千葉哲博, 加藤直也
  • Organizer: 第107回 日本消化器病学会総会
• [Presentation] 血清FGF19・VEGF値からみた進行肝癌症例におけるソラフェニブ及びレンバチニブの治療反応性と病勢進行に伴う変化の検討 (2020)
  • Author(s): 神崎洋彰，千葉哲博，加藤直也
  • Organizer: 第43回日本肝臓学会東部会
• [Presentation] 肝細胞癌における可溶型PD-L1の特性および分泌機序の検討 (2020)
  • Author(s): 神崎洋彰，千葉哲博，加藤直也
  • Organizer: 第24回日本肝臓学会大会
• [Presentation] 同種移植肝癌モデルマウスを用いたマルチキナーゼ阻害剤の肝癌微小環境への影響の検討 (2020)
  • Author(s): 金山健剛，千葉哲博，加藤直也
  • Organizer: 第56回日本肝臓学会総会
• [Presentation] 肝癌のMKI治療におけるFG19及びVEGFの血清バイオマーカーとしての意義 (2020)
  • Author(s): 千葉哲博，神崎洋彰，加藤直也
  • Organizer: 第56回日本肝癌研究会
• [Presentation] Serum angiopoietin 2 as a diagnostic and prognostic biomarkers in hepatocellular carcinoma. (2020)
  • Author(s): Chiba T，Ao J，Kanzaki H，Shibata S，Kakiuchi R，Sakaue A，Qiang N，Ma Y，Kanayama K, Kojima R，Kusakabe Y，Nakamura M，Saito T，Nakagawa R，Kondo T，Ogasawara S，Suzuki E，Muroyama R，Kondo T，Maruyama H，Kato J，Kato N.
  • Organizer: 米国肝臓学会議 2020
  • Int'l Joint Research
• [Presentation] Potential as biomarkers of circulating cell-free DNA. (2020)
  • Author(s): Kanzaki H，Chiba T，Unozawa H，Iwanaga T，Sakuma T，Fujita N，Koroki K，Kobayashi K，Kiyono S，Nakmaura M，Kanogawa N，Kondo T，Saito T，Nakagawa R，Ogasawara S，Suzuki E，Muroyama R，Nakamoto S，Tawada A，Kato N.
  • Organizer: 米国肝臓学会議 2020
  • Int'l Joint Research
• [Presentation] An improved diet-induced murine model for nonalcoholic fatty liver disease with rapid progression of steatohepatitis and fibrosis. (2020)
  • Author(s): Nakmaura M，Chiba T，Sakuma T，Iwanaga T，Fujita N，Ao J，Ma Y，Kanayama K， Kanzaki H，Koroki K，Kobayashi K，Nakagawa R，Kanogawa N，Kiyono S，Kondo T， Saito T，Ogasawara S，Ooka Y，Suzuki E，Nakamoto S，Muroyama R，Kato N.
  • Organizer: 米国肝臓学会議 2020
  • Int'l Joint Research