Establishment new HCC derived cell lines that support efficient hepatitis virus replication.

• Project/Area Number: 26670378
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Kanazawa University
• Principal Investigator: HONDA Masao 金沢大学, 保健学系, 教授 (00272980)
• Co-Investigator(Renkei-kenkyūsha): YAMASHITA Taro 金沢大学, 附属病院, 助教 (90377432) ; SHIMAKAMI Tetsuro 金沢大学, 附属病院, 助教 (50436820) ; SHIRASAKI Takayoshi 金沢大学, 保健学系, 助教 (50547180)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ウイルス培養細胞 / 幹細胞マーカー / 自然免疫 / 癌 / 感染症 / ウイルス

Outline of Final Research Achievements

We established a new cell line that is positive for cancer stem cell marker, EpCAM and supports efficient HCV replication and infection (JFH-1 and HJ3-5), from HCC tissue infected with genotype 1b HCV. KH cells have intact RIG-I sequence and produce IFN signaling, therefore, HCV replication once decline and increased again after infection. TP53 status of KH is wild and established tumor formation in NOD-SCID mice. Thus, we established a new HCC cell line that support efficient HCV replication and infection. Further studies should be needed to establish KH derived cells that support an efficient genotype 1b HCV replication.

Research Products

• [Journal Article] Post-progression survival and progression-free survival in patients with advanced hepatocellular carcinoma treated by sorafenib. (2016)
  • Author(s): Terashima T, Yamashita T, Takata N, Nakagawa H, Toyama T, Arai K, Kitamura K, Yamashita T, Sakai Y, Mizukoshi E, Honda M, Kaneko S.
  • Journal Title: Hepatol Res. Volume: 印刷中 Issue: 7 Pages: 650-656
  • DOI: 10.1111/hepr.12601
  • NAID: 120005704530
  • Peer Reviewed / Open Access
• [Journal Article] Small tRNA-derived RNAs are increased and more abundant than microRNAs in chronic hepatitis B and C. (2015)
  • Author(s): Selitsky SR, Baran-Gale J, Honda M, Yamane D, Masaki T, Fannin EE, Guerra B, Shirasaki T, Shimakami T, Kaneko S, Lanford RE, Lemon SM, Sethupathy P.
  • Journal Title: Sci Rep. Volume: 5 Issue: 1 Pages: 7675-7675
  • DOI: 10.1038/srep07675
  • Peer Reviewed / Open Access
• [Journal Article] Characteristics of hepatic fatty acid compositions in patients with nonalcoholic steatohepatitis. (2015)
  • Author(s): Yamada K, Mizukoshi E, Sunagozaka H, Arai K, Yamashita T, Takeshita Y, Misu H, Takamura T, Kitamura S, Zen Y, Nakanuma Y, Honda M, Kaneko S.
  • Journal Title: Liver Int. Volume: 35(2) Issue: 2 Pages: 582-90
  • DOI: 10.1111/liv.12685
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide association study identifies a PSMD3 variant associated with neutropenia in interferon-based therapy for chronic hepatitis C. (2015)
  • Author(s): Iio E, Matsuura K, Nishida N, Maekawa S, Enomoto N, Nakagawa M, Sakamoto N, Yatsuhashi H et al.
  • Journal Title: Hum Genet Volume: 134 Issue: 3 Pages: 279-289
  • DOI: 10.1007/s00439-014-1520-7
  • Peer Reviewed / Open Access
• [Journal Article] TSU-68 Ameliorates Hepatocellular Carcinoma Growth by Inhibiting Microenvironmental Platelet-derived Growth Factor Signaling. (2015)
  • Author(s): Hara Y, Yamashita T, Oishi N, Nio K, Hayashi T, Nomura Y, Yoshida M, Hayashi T, Hashiba T, Asahina Y, Kondo M, Okada H, Sunagozaka H, Honda M, Kaneko S.
  • Journal Title: Anticancer Res. Volume: 35 Pages: 1423-1431
  • Peer Reviewed / Open Access
• [Journal Article] Inflammatory Features of Pancreatic Cancer Highlighted byMonocytes/Macrophages and CD4+ T cells with Clinical Impact. (2015)
  • Author(s): Komura T, Sakai Y, Harada K, Kawaguchi K, Takabatake H, Kitagawa H, Wada T, Honda M, Ohta T, Nakanuma Y, Kaneko S.
  • Journal Title: Cancer Sci. Volume: 106(6) Issue: 6 Pages: 672-86
  • DOI: 10.1111/cas.12663
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of microRNA-214 ameliorates hepatic fibrosis and tumor incidence in platelet-derived growth factor C transgenic mice. (2015)
  • Author(s): H Okada, M Honda, JS Campbell, K Takegoshi, Y Sakai, T Yamashita, T Shirasaki, R Takabatake, M Nakamura, T Tanaka, S Kaneko.
  • Journal Title: Cancer Sci Volume: 106 Issue: 9 Pages: 1143-1152
  • DOI: 10.1111/cas.12730
  • NAID: 120005830608
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Response to Importance of confounding factors in assessing fatty acid compositions in patients with non-alcoholic steatohepatitis (2015)
  • Author(s): Yamada K, Mizukoshi E, Sunagozaka H, Arai K, Yamashita T, Takeshita Y, Misu H, Takamura T, Kitamura S, Zen Y, Nakanuma Y, Honda M, Kaneko S
  • Journal Title: Liver Int Volume: 35 Issue: 6 Pages: 1773-1773
  • DOI: 10.1111/liv.12755
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Defeating EpCAM(+) liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma. (2015)
  • Author(s): Nio K, Yamashita T, Okada H, Kondo M, Hayashi T, Hara Y, Nomura Y, Zeng SS, Yoshida M, Hayashi T, Sunagozaka H, Oishi N, Honda M, Kaneko S
  • Journal Title: J. Hepatology Volume: 5 Issue: 5 Pages: 1164-72
  • DOI: 10.1016/j.jhep.2015.06.009
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transcriptomic Analysis of Chronic Hepatitis B and C and Liver Cancer Reveals MicroRNA-Mediated Control of Cholesterol Synthesis Programs. (2015)
  • Author(s): Selitsky SR, Dinh TA, Toth CL, Kurtz CL, Honda M, Struck BR, Kaneko S, Vickers KC, Lemon SM, Sethupathy P.
  • Journal Title: MBio. Volume: 6 Issue: 6
  • DOI: 10.1128/mbio.01500-15
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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.
  • Journal Title: Hepatol Res. Volume: - Issue: 8 Pages: 846-855
  • DOI: 10.1111/hepr.12423
  • Peer Reviewed / Open Access
• [Journal Article] Blood neutrophil to lymphocyte ratio as a predictor in patients with advanced hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy. (2014)
  • Author(s): Terashima T, Yamashita T, Iida N, Yamashita T, Nakagawa H, Arai K, Kitamura K, Kagaya T, Sakai Y, Mizukoshi E, Honda M, Kaneko S.
  • Journal Title: Hepatol Res. Volume: - Issue: 9 Pages: 949-959
  • DOI: 10.1111/hepr.12436
  • Peer Reviewed / Open Access
• [Journal Article] Impaired interferon signaling in chronic hepatitis C patients with advanced fibrosis via the transforming growth factor beta signaling pathway. (2014)
  • Author(s): Shirasaki T, Honda M, Shimakami T, Murai K, Shiomoto T, Okada H, Takabatake R, Tokumaru A, Sakai Y, Yamashita T, Lemon SM, Murakami S, Kaneko S.
  • Journal Title: Hepatology. Volume: 60(5) Issue: 5 Pages: 1519-30
  • DOI: 10.1002/hep.27277
  • Peer Reviewed
• [Journal Article] The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism : a randomised controlled trial (2014)
  • Author(s): Y Takeshita, T Takamura, M Honda, Y Kita, Y Zen, KI Kato, H Misu, T Ota, M Nakamura, K Yamada, H Sunagozaka, K Arai, T Yamashita, E Mizukoshi, S Kaneko
  • Journal Title: Diabetologia Volume: 57(5) Issue: 5 Pages: 878-90
  • DOI: 10.1007/s00125-013-3149-9
  • Peer Reviewed / Open Access
• [Journal Article] P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma. (2014)
  • Author(s): Terashima T, Mizukoshi E, Arai K, Yamashita T, Yoshida M, Ota H, Onishi I, Kayahara M, Ohtsubo K, Kagaya T, Honda M, Kaneko S.
  • Journal Title: Cancer Immunol Immunother. Volume: 63(5) Issue: 5 Pages: 479-89
  • DOI: 10.1007/s00262-014-1529-8
  • NAID: 120005464870
  • Peer Reviewed / Open Access
• [Journal Article] The acyclic retinoid peretinoin inhibits hepatitis C virus replication and infectious virus release in vitro. (2014)
  • Author(s): Shimakami T, Honda M, Shirasaki T, Takabatake R, Liu F, Murai K, Shiomoto T, Funaki M, Yamane D, Murakami S, Lemon SM, Kaneko S.
  • Journal Title: Sci Rep. Volume: 4 Issue: 1 Pages: 4688-4688
  • DOI: 10.1038/srep04688
  • NAID: 120005774911
  • Peer Reviewed / Open Access
• [Journal Article] Hepatic interferon-stimulated genes are differentially regulated in the liver of chronic hepatitis C patients with different interleukin 28B genotypes (2014)
  • Author(s): M Honda, T Shirasaki, T Shimakami, A Sakai, R Horii, K Arai, T Yamashita, Y Sakai, T Yamashita, H Okada, K Murai, M Nakamura, E Mizukoshi, S Kaneko
  • Journal Title: Hepatology Volume: 59(3) Issue: 3 Pages: 828-38
  • DOI: 10.1002/hep.26788
  • NAID: 120005447749
  • Peer Reviewed / Open Access
• [Journal Article] Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma. (2014)
  • Author(s): Yamashita T, Kitao A, Matsui O, Hayashi T, Nio K, Kondo M, Ohno N, Miyati T, Okada H, Yamashita T, Mizukoshi E, Honda M, Nakanuma Y, Takamura H, Ohta T, Nakamoto Y, Yamamoto M, Takayama T, Arii S, Wang XW, Kaneko S
  • Journal Title: Hepatology Volume: in press Issue: 5 Pages: 1674-85
  • DOI: 10.1002/hep.27093
  • Peer Reviewed / Open Access
• [Journal Article] New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia. (2014)
  • Author(s): Nishida N, Sawai H, Kashiwase K, Minami M, Sugiyama M, Seto WK, Yuen MF, Posuwan N, Poovorawan Y, Ahn SH, Han KH, Matsuura K, Tanaka Y, Kurosaki M, Asahina Y, Izumi N, Kang JK, （省略）, Tokunaga K, and Mizokami M
  • Journal Title: PLoS One Volume: 9 Issue: 2 Pages: e86449-e86449
  • DOI: 10.1371/journal.pone.0086449
  • Peer Reviewed / Open Access
• [Journal Article] The transcription factor SALL4 regulates stemness of EpCAM-positive hepatocellular carcinoma. (2014)
  • Author(s): Zeng SS, Yamashita T, Kondo M, Nio K, Hayashi T, Hara Y, Nomura Y, Yoshida M, Hayashi T, Oishi N, Ikeda H, Honda M, and Kaneko S.
  • Journal Title: Journal of Hepatology Volume: 60 Issue: 1 Pages: 127-134
  • DOI: 10.1016/j.jhep.2013.08.024
  • NAID: 120005349158
  • Peer Reviewed
• [Journal Article] Feasibility and efficacy of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma after sorafenib. (2013)
  • Author(s): Terashima T, Yamashita T, Arai K, Sunagozaka H, Kitahara M, Nakagawa H, Kagaya T, Mizukoshi E, Honda M, Kaneko S.
  • Journal Title: Hepatol Res. Volume: Oct 31 Issue: 12 Pages: 1-7
  • DOI: 10.1111/hepr.12266
  • NAID: 120005537892
  • Peer Reviewed / Open Access
• [Presentation] Hepatitis B virus X protein stimulates HBV replication by regulating transcription factors associated with DNA or histone methylation (2015)
  • Author(s): Naoki Oishi, Xuyang Wang, Kazunori Kawaguchi, Masao Honda, Seishi Murakami, Shuichi Kaneko
  • Organizer: AASLD The Liver Meeting 2015
  • Place of Presentation: サンフランシスコ（アメリカ）
  • Year and Date: 2015-11-13
  • Int'l Joint Research
• [Presentation] Peretinoin, an acyclic retinoid, suppresses steatohepatitis and development of tumorigenesis by activated Atg16L1-dependent autophagy in mice fed an atherogenic high-fat diet (2015)
  • Author(s): Hikari Okada, Masao Honda, Kai Takegoshi, Taro Yamashita, Naoto Matsuzawa,Toshinari Takamura, Takuji Tanaka, Shuichi Kaneko
  • Organizer: AASLD The Liver Meeting 2015
  • Place of Presentation: サンフランシスコ（アメリカ）
  • Year and Date: 2015-11-13
  • Int'l Joint Research
• [Presentation] Effective prevention of direct-acting antiviral-resistant hepatitis C virus by combination with LNA-anti-miR-122 therapy in cell culture (2015)
  • Author(s): Fanwei Liu, Tetsuro Shimakami, Kazuhisa Murai, Takayuki Shirasaki, Masaya Funaki, Masao Honda, Hong Tang, Seishi Murakami, Shuichi Kaneko
  • Organizer: 22nd International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: ストラスブール（フランス）
  • Year and Date: 2015-10-09
  • Int'l Joint Research
• [Presentation] LECT2 Specifically Induced by IL28B Regulates Interferon Response and HCV Replication. (2014)
  • Author(s): Shirasaki T, Honda M, Shimakami T, Murai K, Shiomoto T, Misu H, Takamura T, Lemon SM, Murakami S, Kaneko S.
  • Organizer: 21st International Symposium on Hepatitis C Viruses (HCV2014)
  • Place of Presentation: バンフ（カナダ）
  • Year and Date: 2014-09-09