Analysis of hepatitis C-related hepatocellular carcinoma pathogenesis

• Project/Area Number: 24790678
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Chiba University
• Principal Investigator: NAKAMOTO Shingo 千葉大学, 医学(系)研究科(研究院), 助教 (90586596)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ウイルス性肝疾患 / 肝発癌

Research Abstract

It is known that hepatitis C virus (HCV)-related hepatocellular carcinoma development is associated with age. In this study, the effect of sirtuin (SIRT) gene, considered age-related, on HCV-related liver pathogenesis was examined. SIRT gene was down-regulated in the human liver cancerous tissue compared to the non-cancerous tissue. There was no effect of SIRT expression on patients age or gender. HCV replication was independent of SIRT gene inhibition or activation in HCV-replicating liver cancer cells. Cellular senescence determined by beta-galactosidase staining is affected by cellular density and possibly by HCV. Although precise mechanisms remain to be elucidated, there might be a relationship between SIRT gene expression and HCV-related hepatocellular carcinoma.

Research Products

• [Journal Article] Prevalence of hepatitis C virus subgenotypes 1a and 1b in Japanese pa tients : ultra-deep sequencing analysis of HCV NS5B genotype-specific region (2013)
  • Author(s): Wu S., at al.
  • Journal Title: PLoS One. Volume: 8 Issue: 9 Pages: e73615-e73615
  • DOI: 10.1371/journal.pone.0073615
  • Peer Reviewed
• [Journal Article] Different effects of three interferons L on Toll-like receptor-related gene exnression in HepG2 cells (2013)
  • Author(s): Kanda T., et al.
  • Journal Title: Cytokine Volume: 64 Issue: 2 Pages: 577-583
  • DOI: 10.1016/j.cyto.2013.08.010
  • Peer Reviewed
• [Journal Article] Effect of occult hepatitis B virus infection on the early-onset of hepatocellular carcinoma in patients with hepatitis C virus infection (2013)
  • Author(s): Nakano M, Kawaguchi T, Nakamoto S, Kawaguchi A, Kanda T, Imazeki F, Kuromatsu R, Sumie S, Satani M, Yamada S, Torimura T, Kakuma T, Yokosuka O, Sata M
  • Journal Title: Oncol Rep. Volume: 30(5) Issue: 5 Pages: 2049-55
  • DOI: 10.3892/or.2013.2700
  • Peer Reviewed
• [Journal Article] Lipopolysaccharide blocks induction of unfolded protein response in hum an hepatoma cell lines (2013)
  • Author(s): Jiang X., et al.
  • Journal Title: Immunol Lett. Volume: 152 Issue: 1 Pages: 8-19
  • DOI: 10.1016/j.imlet.2013.03.006
  • Peer Reviewed
• [Journal Article] Prevalence of Hepatitis C Virus Subgenotypes 1a and 1b in Japanese Patients: Ultra-Deep Sequencing Analysis of HCV NS5B Genotype-Specific Region. (2013)
  • Author(s): Wu S, Kanda T, Nakamoto S, Jiang X, Miyamura T, Nakatani SM, Ono SK, Takahashi-Nakaguchi A, Gonoi T, Yokosuka O.
  • Journal Title: PLoS One Volume: 8
  • Peer Reviewed
• [Journal Article] Different effects of three interferons L on Toll-like receptor-related gene expression in HepG2 cells. (2013)
  • Author(s): Kanda T, Jiang X, Nakamoto S, Nakamura M, Miyamura T, Wu S, Yokosuka O.
  • Journal Title: Cytokine Volume: 64 Pages: 577-83
  • Peer Reviewed
• [Journal Article] Lipopolysaccharide blocks induction of unfolded protein response in human hepatoma cell lines (2013)
  • Author(s): Jiang X, Kanda T, Tanaka T, Wu S, Nakamoto S, Imazeki F, Yokosuka O.
  • Journal Title: Immunol Lett Volume: 152 Pages: 8-15
  • Peer Reviewed
• [Journal Article] Peginterferon Alfa-2a plus ribavirin in Japanese patients infected with hepatitis C virus genotype 2 who failed previous interferon therapy. (2013)
  • Author(s): Kanda T, Nakamoto S, Nishino T, Takada N, Tsubota A, Kato K, Miyamura T, Maruoka D, Wu S, Tanaka T, Arai M, Mikami S, Fujiwara K, Imazeki F, Yokosuka O.
  • Journal Title: Int J Med Sci Volume: 10 Issue: 1 Pages: 43-49
  • DOI: 10.7150/ijms.5358
  • Peer Reviewed
• [Journal Article] Knockdown of receptor-interacting serine/threonine protein kinase-2 (RIPK2) affects EMT-associated gene expression in human hepatoma cells (2012)
  • Author(s): Wu S, Kanda T, Nakamoto S, Imazeki F, Yokosuka O
  • Journal Title: Anticancer Res. Volume: 32(9) Pages: 3775-83
  • URL: http://ar.iiarjournals.org/content/32/9/3775.long
  • Peer Reviewed
• [Journal Article] Interleukin-29 suppresses hepatitis A and C viral internal ribosomal entry site-mediated translation. (2012)
  • Author(s): Kanda T, Wu S, Kiyohara T, Nakamoto S, Jiang X, Miyamura T, Imazeki F, Ishii K, Wakita T, Yokosuka O.
  • Journal Title: Viral Immunol. Volume: 25 Issue: 5 Pages: 379-86
  • DOI: 10.1089/vim.2012.0021
  • Peer Reviewed
• [Journal Article] Knockdown of receptor-interacting serine/threonine protein kinase-2 (RIPK2) affects EMT-associated gene expression in human hepatoma cells. (2012)
  • Author(s): Wu S, Kanda T, Nakamoto S, Imazeki F, Yokosuka O.
  • Journal Title: Anticancer Res. Volume: 32 Pages: 3775-83
  • Peer Reviewed
• [Journal Article] Hepatitis B virus e antigen physically associates with receptor-interacting serine/threonine protein kinase 2 and regulates IL-6 gene expression. (2012)
  • Author(s): Wu S, Kanda T, Imazeki F, Nakamoto S, Tanaka T, Arai M, Roger T, Shirasawa H, Nomura F, Yokosuka O.
  • Journal Title: The Journal of Infectious Diseases Volume: 206(3) Issue: 3 Pages: 415-420
  • DOI: 10.1093/infdis/jis363
  • Peer Reviewed
• [Presentation] Reactivation of hepatitis B after hematopoietic stem cell transplantation for hematological malignancy (2013)
  • Author(s): Shingo Nakamoto, Tatsuo Kanda, Shuang Wu, Xia Jiang, Tatsuo Miyamura, Fumio Imazeki, Hiroshi Shirasawa, Chiaki Nakaseko, Osamu Yokosuka
  • Organizer: The liver meeting 2013
  • Place of Presentation: Washington D.C. USA
  • Year and Date: 2013-11-03
• [Presentation] 造血幹細胞移植における HBV再活性化に関する検討 (2013)
  • Author(s): 中本晋吾, 神田達郎, 中世古知昭
  • Organizer: 第21回日本消化器関連学会週間
  • Place of Presentation: 東京
  • Year and Date: 2013-10-09
• [Presentation] B型慢性肝炎核酸アナログ製剤反応不良例に対する Ultra Deep Sequenceの解析 (2013)
  • Author(s): 中本晋吾、呉霜、神田達郎、姜霞、宮村達雄、新井誠人、藤原慶一、今関文夫、齋藤謙悟、白澤浩、横須賀收
  • Organizer: 第49回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2013-06-07
• [Presentation] Prevalence of resistance mutations against NS5A inhibitors in DAA-treatment-na〓ve patients infected with HCV G1 in Japan (2013)
  • Author(s): Shingo Nakamoto, Tatsuo Kanda, Shuang Wu, Xia Jiang, Tatsuo Miyamura, Makoto Arai, Keiichi Fujiwara, Kengo Saito, Fumio Imazeki, Hiroshi Shirasawa, Osamu Yokosuka
  • Organizer: Asian Pacific Association for the Study of the Liver
  • Place of Presentation: Singapore
  • Year and Date: 2013-06-07
• [Presentation] B型慢性肝炎核酸アナログ製剤反応不良例に対するUltra Deep Sequenceの解析 (2013)
  • Author(s): 中本晋吾、呉霜、神田達郎、姜霞、宮村達雄、新井誠人、藤原慶一、今関文夫、齋藤謙悟、白澤浩、横須賀收
  • Organizer: 第49回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] 造血幹細胞移植におけるHBV再活性化に関する検討 (2013)
  • Author(s): 中本晋吾、神田達郎、中世古知昭
  • Organizer: 第21回 日本消化器関連学会週間
  • Place of Presentation: 東京
• [Presentation] Reactivation of hepatitis B after hematopoietic stem cell transplantation for hematological malignancy (2013)
  • Author(s): Shingo Nakamoto, Tatsuo Kanda, Shuang Wu, Xia Jiang, Tatsuo Miyamura, Fumio Imazeki, Hiroshi Shirasawa, Chiaki Nakaseko, Osamu Yokosuka
  • Organizer: The 64rd Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: Washington D.C. USA
• [Presentation] The association between DEPDC5 polymorphism and the development of hepatocellular carcinoma in patients with chronic hepatitis C (2012)
  • Author(s): Shingo Nakamoto, Tatsuo Kanda, Shuang Wu, Xia Jiang, Tatsuo Miyamura, Makoto Arai, Keiichi Fujiwara, Kengo Saito, Fumio Imazeki, Hiroshi Shirasawa, Osamu Yokosuka
  • Organizer: The 63rd Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: Boston, MA, USA
  • Year and Date: 2012-11-11
• [Presentation] ASSOCIATION BETWEEN MICA POLYMORPHISM AND THE DEVELOPMENT OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH CHRONIC HEPATITIS C (2012)
  • Author(s): S. Nakamoto, F. Imazeki, T. Kanda, S. Wu, T. Miyamura, A. Tawada, M. Arai, K. Fujiwara, K. Saito, H. Shirasawa, O. Yokosuka
  • Organizer: 47th annual meeting of the European Association for the Study of the Liver
  • Place of Presentation: Barcelona, Spain
• [Presentation] C型慢性肝疾患の肝発癌予測における遺伝子多型の有用性に関する検討 (2012)
  • Author(s): 中本晋吾、今関文夫、神田達郎、呉霜、宮村達雄、太和田暁之、新井誠人、藤原慶一、齋藤謙悟、白澤浩、横須賀收
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: 金沢市
• [Presentation] C型慢性肝炎G1型におけるIFN著効後肝発癌についての検討 (2012)
  • Author(s): 中本晋吾、今関文夫、神田達郎、呉霜、姜霞、宮村達雄、新井誠人、藤原慶一、齋藤謙悟、白澤浩、横須賀收
  • Organizer: 第16回日本肝臓学会大会
  • Place of Presentation: 神戸市
• [Presentation] HCV G1症例におけるウイルス特異的阻害剤耐性変異に関する検討 (2012)
  • Author(s): 中本晋吾、呉霜、神田達郎、姜霞、宮村達雄、新井誠人、藤原慶一、今関文夫、齋藤謙悟、白澤浩、横須賀收
  • Organizer: 第16回日本肝臓学会大会
  • Place of Presentation: 神戸市
• [Presentation] Shingo Nakamoto, Tatsuo Kanda, Shuang Wu, Xia Jiang, Tatsuo Miyamura, Makoto Arai, Keiichi Fujiwara, Kengo Saito, Fumio Imazeki, Hiroshi Shirasawa, Osamu Yokosuka (2012)
  • Author(s): The association between DEPDC5 polymorphism and the development of hepatocellular carcinoma in patients with chronic hepatitis C
  • Organizer: The Liver Meeting 2012
  • Place of Presentation: Boston, MA, USA