Significance of HBV integration in clonal proliferation of hepatocytes

• Project/Area Number: 20590791
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: MINAMI Masahito Kyoto Prefectural University of Medicine, 医学研究科, 講師 (60326220)
• Research Collaborator: MIYAGAWA Masami 京都府立医科大学, 大学院生 ; SENDO Rei 京都府立医科大学, 大学院生 ; KATAYAMA Takayuki 京都府立医科大学, 大学院生
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: B型肝炎ウイルス / 肝発癌 / 組み込み / HBV

Research Abstract

Hepatitis B virus (HBV) DNA can be integrated into the host genome and co-exist after its replication become decreased. In this study we revealed that HBV integration does not occur randomly, but is preferentially located in the certain region of the host genome. In those regions, there are many human genes related to cell proliferation, suggesting that HBV integration plays some role in modulating cell cycle. This mechanism can be related to viral persistence in the host cells and resulting liver carcinogenesis.

Research Products

• [Journal Article] Efficacy of long-term ezetimibe therapy in patients with nonalcoholic fatty liver disease. (2011)
  • Author(s): Park H, Shima T, Yamaguchi K, Mitsuyoshi H, Minami M, Yasui K, Itoh Y, Yoshikawa T, Fukui M, Hasegawa G, Nakamura N, Ohta M, Obayashi H, Okanoue T.
  • Journal Title: J Gastroenterol 46(1) Pages: 101-107
  • NAID: 10029026804
  • Peer Reviewed
• [Journal Article] PEG10 is a probable target for the amplification at 7q21 detected in hepatocellular carcinoma. (2010)
  • Author(s): Tsuji K, Yasui K, Gen Y, Endo M, Dohi O, Zen K, Mitsuyoshi H, Minami M, Itoh Y, Taniwaki M, Tanaka S, Arii S, Okanoue T, Yoshikawa T.
  • Journal Title: Cancer Genet Cytogenet 198 Pages: 118-125
  • Peer Reviewed
• [Journal Article] Interferon and nucleoside analog combination therapy. (2010)
  • Author(s): Minami M, Katayama T, Sendo R, Okanoue T, Yoshikawa T.
  • Journal Title: Clin J Gastroenterol 3 Pages: 69-72
  • Peer Reviewed
• [Journal Article] Hepatic senescence marker protein-30 is involved in the progression of nonalcoholic fatty liver disease. (2010)
  • Author(s): Park H, Ishigami A, Shima T, Mizuno M, Maruyama N, Yamaguchi K, Mitsuyoshi H, Minami M, Yasui K, Itoh Y, Yoshikawa T, Fukui M, Hasegawa G, Nakamura N, Ohta M, Obayashi H, Okanoue T.
  • Journal Title: J Gastroenterol 45(4) Pages: 426-434
  • NAID: 10027215694
  • Peer Reviewed
• [Journal Article] Steatosis and hepatic expression of genes regulating lipid metabolism in Japanese patients infected with hepatitis C virus. (2010)
  • Author(s): Yasui K, Harano Y, Mitsuyoshi H, Tsuji K, Endo M, Nakajima T, Minami M, Itoh Y, Zen Y, Nakanuma Y, Yoshikawa T, Okanoue T.
  • Journal Title: J Gastroenterol 45(1) Pages: 95-104
  • NAID: 10027214026
  • Peer Reviewed
• [Journal Article] Relapse of hepatitis C in a pegylated-interferon-alpha-2b plus ribavirin-treated sustained virological responder. (2010)
  • Author(s): Fujii H, Itoh Y, Ohnishi N, Sakamoto M, Ohkawara T, Sawa Y, Nishida K, Nishimura T, Yamaguchi K, Yasui K, Minami M, Okanoue T, Ohkawara Y, Yoshikawa T.
  • Journal Title: Hepatol Res 40(6) Pages: 654-660
  • Peer Reviewed
• [Journal Article] The fatty acid composition of plasma cholesteryl esters and estimated desaturase activities in patients with nonalcoholic fatty liver disease and the effect of long-term ezetimibe therapy on these levels. (2010)
  • Author(s): Park H, Hasegawa G, Shima T, Fukui M, Nakamura N, Yamaguchi K, Mitsuyoshi H, Minami M, Yasui K, Itoh Y, Yoshikawa T, Kitawaki J, Ohta M, Obayashi H, Okanoue T.
  • Journal Title: Clin Chim Acta 411(21-22) Pages: 1735-1740
  • Peer Reviewed
• [Journal Article] Nonalcoholic steatohepatitis and increased risk of chronic kidney disease. (2010)
  • Author(s): Yasui K, Sumida Y, Mori Y, Mitsuyoshi H, Minami M, Itoh Y, Kanemasa K, Matsubara H, Okanoue T, Yoshikawa T.
  • Journal Title: Metabolism 60(5) Pages: 735-739
  • Peer Reviewed
• [Journal Article] Lower circulating levels of dehydroepiandrosterone, independ- ent of insulin resistance, is an important determinant of severity of non-alcoholic steatohepatitis in Japanese patients. (2010)
  • Author(s): Sumida Y, Yonei Y, Kanemasa K, Hara T, Inada Y, Sakai K, Imai S, Hibino S, Yamaguchi K, Mitsuyoshi H, Yasui K, Minami M, Itoh Y, Naito Y, Yoshikawa T, Okanoue T.
  • Journal Title: Hepatol Res 40(9) Pages: 901-910
  • Peer Reviewed
• [Journal Article] PEG10 is a probable target for the amplification at 7q21 detected in hepatocellular carcinoma. (2010)
  • Author(s): Tsuji K, Yasui K, Gen Y, Endo M, Dohi O, Zen K, Mitsuyoshi H, Minami M, Itoh Y, Taniwaki M, Tanaka S, Arii S, Okanoue T, Yoshikawa T.
  • Journal Title: Cancer Genet Cytogenet Volume: 198 Pages: 118-125
  • Peer Reviewed
• [Journal Article] Infrequent amplification of JUN in hepatocellular carcinoma. (2009)
  • Author(s): Endo M, Yasui K, Nakajima T, Gen Y, Tsuji K, Dohi O, Zen K, Mitsuyoshi H, Minami M, Itoh Y, Taniwaki M, Tanaka S, Arii S, Okanoue T, Yoshikawa T.
  • Journal Title: Anticancer Res 29 Pages: 4894-4898
  • Peer Reviewed
• [Journal Article] ERK5 is a target for gene amplification at 17p11 and promotes cell growth in hepatocellular carcinoma by regulating mitotic entry. (2009)
  • Author(s): Zen K, Yasui K, Nakajima T, Zen Y, Zen K, Gen Y, Mitsuyoshi H, Minami M, Mitsufuji S, Tanaka S, Itoh Y, Nakanuma Y, Taniwaki M, Arii S, Okanoue T, Yoshikawa T.
  • Journal Title: Genes Chromosomes Cancer 48(2) Pages: 109-120
  • Peer Reviewed
• [Journal Article] Predictive values of amino acid sequences of the core and NS5A regions in antiviral therapy for hepatitis C : a Japanese multi-center study. (2009)
  • Author(s): Okanoue T, Itoh Y, Hashimoto H, Yasui K, Minami M, Takehara T, Tanaka E, Onji M, Toyota J, Chayama K, Yoshioka K, Izumi N, Akuta N, Kumada H.
  • Journal Title: J Gastroenterol 44(9) Pages: 952-963
  • NAID: 10025581408
  • Peer Reviewed
• [Journal Article] Predictive values of amino acid sequences of the core and NS5A regions in antiviral therapy for hepatitis C : a Japanese multi-center study. (2009)
  • Author(s): Miyagawa M, Minami M, Fujii K, Sendo R, Mori K, Shimizu D, Nakajima T, Yasui K, Itoh Y, Taniwaki M, Okanoue T, Izumi N, Akuta N, Kumada H.
  • Journal Title: J Gastroenterol 44(9) Pages: 952-963
  • NAID: 10025581408
  • Peer Reviewed
• [Journal Article] Infrequent amplification of JUN in hepatocellular carcinoma (2009)
  • Author(s): Endo M, Yasui K, Nakajima T, Gen Y, Tsuji K, Dohi O, Zen K, Mitsuyoshi H, Minami M, Itoh Y, Taniwaki M, Tanaka S, Arii S, Okanoue T, Yoshikawa T.
  • Journal Title: Anticancer Res 29 Pages: 4989-4994
  • Peer Reviewed
• [Journal Article] Molecular characterization of a variant virus that caused de novo hepatitis B without elevation of hepatitis B surface antigen after chemotherapy with rituximab. (2008)
  • Author(s): Miyagawa M, Minami M, Fujii K, Sendo R, Mori K, Shimizu D, Nakajima T, Yasui K, Itoh Y, Taniwaki M, Okanoue T, Yoshikawa T.
  • Journal Title: J Med Virol 80 Pages: 2069-2078
  • Peer Reviewed
• [Journal Article] CREB3L4, INTS3, and SNAPAP are targets for the 1q21 amplicon frequently detected in hepatocellular carcinoma. (2008)
  • Author(s): Inagaki Y, Yasui K, Endo M, Nakajima T, Zen K, Tsuji K, Minami M, Tanaka S, Taniwaki M, Itoh Y, Arii S, Okanoue T.
  • Journal Title: Cancer Genet Cytogenet 180(1) Pages: 30-36
  • Peer Reviewed
• [Journal Article] Activation of B-Myb by E2F1 in hepatocellular carcinoma. (2008)
  • Author(s): Nakajima T, Yasui K, Zen K, Inagaki Y, Fujii H, Minami M, Tanaka S, Taniwaki M, Itoh Y, Arii S, Inazawa J, Okanoue T.
  • Journal Title: Hepatol Res 38(9) Pages: 886-895
  • NAID: 10021946383
  • Peer Reviewed
• [Journal Article] A novel amplification target, ARHGAP5, promotes cell spreading and migration by negatively regulating RhoA in Huh-7 hepatocellular carcinoma cells. (2008)
  • Author(s): Gen Y, Yasui K, Zen K, Nakajima T, Tsuji K, Endo M, Mitsuyoshi H, Minami M, Itoh Y, Tanaka S, Taniwaki M, Arii S, Okanoue T, Yoshikawa T.
  • Journal Title: Cancer Lett 275(1) Pages: 27-34
  • Peer Reviewed
• [Journal Article] Non-prescription supplement-induced hepatitis with hyperferritinemia and mutation (H63D) in the HFE gene. (2008)
  • Author(s): Fujii H, Takagaki N, Yoh T, Morita A, Ohkawara T, Yamaguchi K, Minami M, Sawa Y, Okanoue T, Ohkawara Y, Itoh Y.
  • Journal Title: Hepatol Res 38(3) Pages: 319-323
  • NAID: 10024147708
  • Peer Reviewed
• [Journal Article] Evidence of oxidative stress as a cofactor in the development of insulin resistance in patients with chronic hepatitis C. (2008)
  • Author(s): Mitsuyoshi H, Itoh Y, Sumida Y, Minami M, Yasui K, Nakashima T, Okanoue T.
  • Journal Title: Hepatol Res 38(4) Pages: 348-353
  • NAID: 10024147806
  • Peer Reviewed
• [Journal Article] Guidelines for the antiviral therapy of hepatitis C virus carriers with normal serum aminotransferase based on platelet counts. (2008)
  • Author(s): Okanoue T, Itoh Y, Minami M, Hashimoto H, Yasui K, Yotsuyanagi H, Takehara T, Kumada T, Tanaka E, Nishiguchi S, Izumi N, Sata M, Onji M, Yamada G, Okita K, Kumada H.
  • Journal Title: Hepatol Res 38(1) Pages: 27-36
  • NAID: 10020116834
  • Peer Reviewed
• [Journal Article] Analysis of hepatic genes involved in the metabolism of fatty acids and iron in nonalcoholic fatty liver disease. (2008)
  • Author(s): Mitsuyoshi H, Yasui K, Harano Y, Endo M, Tsuji K, Minami M, Itoh Y, Okanoue T, Yoshikawa T.
  • Journal Title: Hepatol Res 38(4) Pages: 348-353
  • NAID: 10025325411
  • Peer Reviewed
• [Journal Article] ウイルス性肝炎 : B型肝炎3 核酸アナログ製剤による治療. (2008)
  • Author(s): 南 祐仁.
  • Journal Title: 治療学 42 Pages: 25-28
• [Journal Article] Molecular characterization of a variant virus that caused de novo hepatitis B without elevation of hepatitis Bsurface antigen after chemotherapy with rituximab. (2008)
  • Author(s): Miyagawa M, Minami M, Fujii K, Sendo R, Mori K, Shimizu D, Nakajima T, Yasui K, Itoh Y, Taniwaki M, Okanoue T, Yoshikawa T.
  • Journal Title: Journal of Medical Virology 80(12) Pages: 2069-2078
  • Peer Reviewed
• [Presentation] 染色体脆弱部位は、HBV感染肝細胞におけるHBV DNA組み込みの標的部位である (2009)
  • Author(s): 千藤麗, 南祐仁, 宮川昌巳, 藤井恒太, 安居幸一郎, 伊藤義人, 嘉数直樹, 岡上武, 吉川敏一
  • Organizer: 第45回日本肝臓学会総会.ワークショップ4 ; B型肝炎の基礎と臨床
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-04
• [Presentation] 染色体脆弱部位は、HBV感染肝細胞におけるHBV DNA組み込みの標的部位である (2009)
  • Author(s): 千藤麗, 南祐仁, 宮川昌巳, 藤井恒太, 安居幸一郎, 伊藤義人, 嘉数直樹, 岡上武, 吉川敏一
  • Organizer: 第45回日本肝臓学会総会.ワークショップ4;B型肝炎の某礎と臨床
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-04
• [Book] 肝硬変の成因別実態2008(肝硬変の成因別実態と肝癌合併例の検討.)東京 (2008)
  • Author(s): 山口寛二, 伊藤義人, 新美敏久, 光吉博則, 安居幸一郎, 南祐仁, 岩井眞樹, 岡上武, 吉川敏一
  • Publisher: 中外医学社
• [Book] 肝硬変の成因別実態と肝癌合併例の検討. 肝硬変の成因別実態2008. (2008)
  • Author(s): 山口寛二, 伊藤義人, 新美敏久, 光吉博則, 安居幸一郎, 南 祐仁, 岩井眞樹, 岡上武, 吉川敏一.
  • Publisher: 中外医学社, 東京