Investigation about the role of WT1 and PKR for the carcinogenesis or progression of hepatocellular carcinoma

• Project/Area Number: 21590848
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Ehime University
• Principal Investigator: HIASA Yoichi 愛媛大学, 大学院・医学系研究科, 准教授 (70314961)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: WT1遺伝子 / PKR / 肝細胞癌 / アポトーシス / C型肝炎ウイルス / interleukin-8 / Caspase / siRNA / PCRアレイ / H77 / Annexin V / HCV粒子生成可能複製系 / 細胞増殖 / 細胞接着因子

Research Abstract

We investigated about the role of Wilms' tumor 1(WT1) gene and Protein kinase R(PKR), which over-expressed in the tissue of hepatocellular carcinoma(HCC). The expression of WT1 in HCC was related with oncogenesis, recurrence, tumor growth and prognosis. The PKR was induced by interferon, as well as by ribavirin, both drugs are well known as anti-hepatitis C virus(HCV) drugs. The interaction of PKR and HCV would have some possibilities related with the hepatocarcinogenesis induced by HCV, and overexpressed WT1 and PKR might be therapeutic target of HCC.

Research Products

• [Journal Article] Rivabirin regulates hepatitis C virus replication through enhancing interferon-stimulated genes and interleukin 8 (2012)
  • Author(s): Tokumoto Y, Hiasa Y, Uesugi K, 他7名
  • Journal Title: J Infect Dis
  • Peer Reviewed
• [Journal Article] Ribavirin regulates hepatitis C virus replication through enhancing interferon-stimulated genes and interleukin 8 (2012)
  • Author(s): Tokumoto Y, Hiasa Y, Uesugi K, 他7名、2番目
  • Journal Title: Journal of Infectious Diseases Volume: 205 Issue: 7 Pages: 1121-1130
  • DOI: 10.1093/infdis/jis025
  • Peer Reviewed
• [Journal Article] Splenic elasticity measured with real-time tissue elastography is a marker of portal hypertension (2011)
  • Author(s): Hirooka M, Ochi H, Hiasa Y, 他6名
  • Journal Title: Radiology Volume: 261巻 Pages: 960-968
  • Peer Reviewed
• [Journal Article] Hepatic elasticity in patients with ascites : evaluation with real-time tissue elastography (2011)
  • Author(s): Hirooka M, Koizumi Y, Hiasa Y, 他4名
  • Journal Title: AJR Am J Roentgenol Volume: 196巻
  • Peer Reviewed
• [Journal Article] Aerobic exercise improves insulin resistance and decreases body fat and serum levels of leptin in patients with hepatitis C virus (2011)
  • Author(s): Konishi I, Hiasa Y, Tokumoto Y, 他5名
  • Journal Title: Hepatol Res Volume: 41巻 Pages: 928-935
  • Peer Reviewed
• [Journal Article] Sustained virological response of patients with hepatitis C virus genotype 2 depends on pegylated interferon compliance (2011)
  • Author(s): Watanabe T, Konishi I, Hiasa Y, 他12名
  • Journal Title: Hepatol Res Volume: 41巻 Pages: 720-730
  • Peer Reviewed
• [Journal Article] Genome-wide association study identified ITPA/DDRGK1 variants reflecting thrombocytopenia in pegylated interferon and ribavirin therapy for chronic hepatitis C (2011)
  • Author(s): Tanaka Y, Kurosaki M, Hiasa Y, 他19名
  • Journal Title: Hum Mol Genet Volume: 20巻 Pages: 3507-3516
  • Peer Reviewed
• [Journal Article] Association of IL28B variants with response to pegylated-interferon alpha plus ribavirin combination therapy reveals intersubgenotypic differences between genotypes 2a and 2b (2011)
  • Author(s): Sakamoto N, Nakagawa M, Hiasa Y, 他17名
  • Journal Title: J Med Virol Volume: 83巻 Pages: 871-878
  • Peer Reviewed
• [Journal Article] Liver Fibrosis in Patients with Chronic Hepatitis C : Noninvasive Diagnosis by Means of Real-time Tissue Elastography-Establishment of the Method for Measurement (2011)
  • Author(s): Koizumi Y, Hirooka M, Hiasa Y, 他6名
  • Journal Title: Radiology Volume: 258巻 Pages: 610-617
  • Peer Reviewed
• [Journal Article] Factors predictive of sustained virological response following 72 weeks of combination therapy for genotype 1b hepatitis C (2011)
  • Author(s): Chayama K, Hayes CN, Hiasa Y, 他14名
  • Journal Title: J Gastroenterol Volume: 46巻 Pages: 545-555
  • Peer Reviewed
• [Journal Article] Splenic elasticity measured with real-time tissue elastography is a marker of portal hypertension (2011)
  • Author(s): Hirooka M, Ochi H, Hiasa Y, 他6名, 8番目
  • Journal Title: Radiology Volume: 261 Issue: 3 Pages: 960-968
  • DOI: 10.1148/radiol.11110156
  • Peer Reviewed
• [Journal Article] Hepatic elasticity in patients with ascites : evaluation with real-time tissue elastography (2011)
  • Author(s): Hirooka M, Koizumi Y, Hiasa Y, 他4名, 3番目
  • Journal Title: AJR American Journal of Roentgenology Volume: 196 Issue: 6 Pages: W766-W771
  • DOI: 10.2214/ajr.10.4867
  • Peer Reviewed
• [Journal Article] Accumulation of refractory factors for pegylated interferon plus ribavirin therapy in older female patients with chronic hepatitis C (2010)
  • Author(s): Chayama K, Hayes CN, Hiasa Y, 他14名
  • Journal Title: Hepatol Res Volume: 40巻 Pages: 1155-1167
  • Peer Reviewed
• [Journal Article] Immune modulator and antiviral potential of dendritic cells pulsed with both hepatitis B surface antigen and core antigen for treating chronic HBV infection (2010)
  • Author(s): Akbar SM, Yoshida O, Hiasa Y, 他5名
  • Journal Title: Antivir Ther Volume: 15巻 Pages: 887-895
  • Peer Reviewed
• [Journal Article] Variability of the polymerase gene(NS5B) in HCV-infected women (2010)
  • Author(s): Blackard JT, Ma G, Hiasa Y, 他8名
  • Journal Title: J Clin Microbiol Volume: 48巻 Pages: 4256-4259
  • Peer Reviewed
• [Journal Article] Persistent expression of the full genome of hepatitis C virus in B cells induces spontaneous development of B-cell lymphomas in vivo (2010)
  • Author(s): Kasama Y, Sekiguchi S, Hiasa Y, 他8名
  • Journal Title: Blood Volume: 116巻 Pages: 4926-4933
  • Peer Reviewed
• [Journal Article] Safety and immunogenicity of hepatitis B surface antigen-pulsed dendritic cells in patients with chronic hepatitis B (2010)
  • Author(s): Akbar SM, Furukawa S, Hiasa Y, 他3名
  • Journal Title: J Viral Hepat Volume: 18巻 Pages: 408-414
  • Peer Reviewed
• [Journal Article] Mechanism of restoration of immune responses of patients with chronic hepatitis B during lamivudine therapy : increased antigen processing and presentation by dendritic cells (2010)
  • Author(s): Akbar SM, Horiike N, Hiasa Y, 他5名
  • Journal Title: J Viral Hepat Volume: 18巻 Pages: 200-205
  • Peer Reviewed
• [Journal Article] Impaired dendritic cell functions disrupt antigen-specific adaptive immune responses in mice with nonalcoholic fatty liver disease (2010)
  • Author(s): Miyake T, Akbar SM, Hiasa Y, 他5名
  • Journal Title: J Gastroenterol Volume: 45巻 Pages: 859-867
  • Peer Reviewed
• [Journal Article] Mass reduction by radiofrequency ablation before hepatic arterial infusion chemotherapy improved prognosis for patients with huge hepatocellular carcinoma and portal vein thrombus (2010)
  • Author(s): Hirooka M, Koizumi Y, Hiasa Y, 他5名
  • Journal Title: AJR Am J Roentgenol Volume: 194巻
  • Peer Reviewed
• [Journal Article] Liver Fibrosis in Patients with Chronic Hepatitis C : Noninvasive Diagnosis by Means of Real-time Tissue Elastography--Establishment of the Method for Measurement (2010)
  • Author(s): Koizumi Y, Hirooka M, Hiasa Y, (他6名、8番目)
  • Journal Title: Radiology Volume: 258 Pages: 610-617
  • Peer Reviewed
• [Journal Article] Variability of the polymerase gene (NS5B) in hepatitis C virus-infected women (2010)
  • Author(s): Blackard JT, Ma G, Hiasa Y, (他8名、7番目)
  • Journal Title: Journal of Clinical Microbiology Volume: 48 Pages: 4256-4259
  • Peer Reviewed
• [Journal Article] Persistent expression of the full genome of hepatitis C virus in B cells induces spontaneous development of B-cell lymphomas in vivo (2010)
  • Author(s): Kasama Y, Sekiguchi S, Hiasa Y, (他8名、9番目)
  • Journal Title: Blood Volume: 116 Pages: 4926-4933
  • Peer Reviewed
• [Journal Article] Hepatocellular carcinoma for the non-specialist (2009)
  • Author(s): Kumagi T, Hiasa Y, Hirschfield GM
  • Journal Title: BMJ Volume: 339巻 Pages: 1366-1370
  • Peer Reviewed
• [Journal Article] Radiofrequency ablation therapy for hepatocellular carcinoma in elderly patients (2009)
  • Author(s): Hiraoka A, Michitaka K, Hiasa Y, 他16名
  • Journal Title: J Gastroenterol Hepatol Volume: 25巻 Pages: 403-407
  • Peer Reviewed
• [Journal Article] Etiology of liver cirrhosis in Japan : a nationwide survey (2009)
  • Author(s): Michitaka K, Nishiguchi S, Hiasa Y, 他3名
  • Journal Title: J Gastroenterol Volume: 45巻 Pages: 86-94
  • Peer Reviewed
• [Journal Article] Genome-wide association of IL28B with response to pegylated interferon-αand ribavirin therapy for chronic hepatitis C (2009)
  • Author(s): Tanaka Y, Nishida N, Hiasa Y, 他26名
  • Journal Title: Nat Genet Volume: 48巻 Pages: 1647-1650
  • Peer Reviewed
• [Journal Article] Diabetes pattern on the 75 g oral glucose tolerance test is a risk factor for hepatocellular carcinoma in patients with hepatitis C virus (2009)
  • Author(s): Konishi I, Hiasa Y, Shigematsu S, 他7名
  • Journal Title: Liver Int Volume: 29巻 Pages: 1194-1201
  • Peer Reviewed
• [Journal Article] Diabetes pattern on the 75g oral glucose tolerance test is a risk factor for hepatocellular carcinoma in patients with hepatitis C virus (2009)
  • Author(s): Konishi I, Hiasa Y, Shigematsu S, 他7名, 2番目
  • Journal Title: Liver International 29 Pages: 1194-1201
  • Peer Reviewed
• [Journal Article] Genome-wide association of IL28B with response to pegylated interferon-α and ribavirin therapy for chronic hepatitis C (2009)
  • Author(s): Tanaka Y, Nishida N, Hiasa Y, 他26名, 18番目
  • Journal Title: Nature Genetics 48 Pages: 1647-1650
  • Peer Reviewed
• [Journal Article] Hepatocellular carcinoma for the non-specialist (2009)
  • Author(s): Kumagi T, Hiasa Y, Hirschfield GM
  • Journal Title: BMJ 339 Pages: 1366-1370
  • Peer Reviewed
• [Presentation] Characterization of ZNF689 in Human Hepatocellular Carcinoma as a Novel Target for Chemotherapy (2011)
  • Author(s): Shigematsu S, Hiasa Y, Fukuda S, 他3名
  • Organizer: The 62th AASLD
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-11-04
• [Presentation] Characterization of ZNF689 in Human Hepatocellular Carcinoma as a Novel Target for Chemotherapy (2011)
  • Author(s): Shigematsu S, Hiasa Y, Fukuda S, 他3名、2番目
  • Organizer: The 62th American association for the study of liver disease
  • Place of Presentation: アメリカ合衆国、サンフランシスコ
  • Year and Date: 2011-11-04
• [Presentation] Up-regulated Wilms' tumor 1 gene functions in anti-apoptosis : potential therapeutic target for hepatocellular carcinoma (2010)
  • Author(s): Uesugi K, Koizumi Y, Hiasa Y, 他8名
  • Organizer: The 61th AASLD
  • Place of Presentation: Boston, USA
  • Year and Date: 2010-11-01
• [Presentation] Up-regulated Wilms' tumor 1 gene functions in anti-apoptosis : potential therapeutic target for hepatocellular carcinoma (2010)
  • Author(s): Uesugi K, Koizumi Y, Hiasa Y, (他8名、3番目)
  • Organizer: The 61th American association for the study of liver disease
  • Place of Presentation: アメリカ合衆国、ボストン
  • Year and Date: 2010-11-01
• [Presentation] Decrease of SOCS-3 by ME3738 contributes to its synergistic anti-HCV effects when combined with type I interferon (2009)
  • Author(s): Hiasa Y, Tokumoto Y, Konishi I, 他4名
  • Organizer: The 60th AASLD
  • Place of Presentation: Boston, USA
  • Year and Date: 2009-11-03
• [Presentation] Decrease of SOCS-3 by ME3738 contributes to its synergistic anti-HCV effects when combined with type I interferon (2009)
  • Author(s): Hiasa Y, Tokumoto Y, Konishi I, 他4名, 1番目
  • Organizer: The 60th American association for the study of liver disease
  • Place of Presentation: アメリカ合衆国、ボストン
  • Year and Date: 2009-11-03
• [Book] 動物モデルによるHBV増殖とその応用B型肝炎ウイルス研究の進歩 (2011)
  • Author(s): 日浅陽一、恩地森一
  • Publisher: 日本臨床社
• [Book] 新時代のウイルス性肝炎学III B型肝炎3)動物モデルによるHBV増殖とその応用 (2011)
  • Author(s): 日浅陽一、恩地森一
  • Publisher: 日本臨牀社
• [Book] クリニカルトピックスWilms' tumor 1遺伝子と肝細胞癌 (2010)
  • Author(s): 日浅陽一、上杉和寛、恩地森一
  • Publisher: BIO Clinica
• [Patent(Industrial Property Rights)] SEP(splenic elasticity for portal hypertension) score (2011)
  • Inventor(s): 日浅陽一、廣岡昌史、恩地森一
  • Industrial Property Rights Holder: 日浅陽一、廣岡昌史、恩地森一
  • Industrial Property Number: 2011-130701
  • Filing Date: 2011-06-01
• [Patent(Industrial Property Rights)] SEP (splenic elasticity for portal hypertension) score (2011)
  • Inventor(s): 日浅陽一、廣岡昌史、恩地森一
  • Industrial Property Rights Holder: 日浅陽一、廣岡昌史、恩地森一
  • Industrial Property Number: 2011-130701
  • Filing Date: 2011-06-01