2000 Fiscal Year Final Research Report Summary
Therapetic strategy for chronic hepatitis C by inducing apoptosis of hepatocyte infected with hepatitis C virus
| Project/Area Number |
11470132
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Osaka University |
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Principal Investigator |
HAYASHI Norio Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (00144478)
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| Co-Investigator(Kenkyū-buntansha) |
MOCHIZUKI Kiyosi Osaka University Hospital, Clinical Staff, 医学部・附属病院, 医員
HIRAMATSU Naoki Osaka University Hospital, Clinical Staff, 医学部・附属病院, 医員
SASAKI Yutaka Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (70235282)
OKAWA Kazuyoshi Osaka University Hospital, Clinical Staff, 医学部・附属病院, 医員
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| Project Period (FY) |
1999 – 2000
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| Keywords | Hepatitis C virus / Apoptosis / Cell cycle / Hepatocyte / Core / Microarray |
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| Research Abstract |
To investigate influence of hepatitis C virus (HCV) infection on hepatocyte, we established several permanent hepatocyte clones that express HCV core gene. Microarray analysis of these clones revealed a couple of gene of which expression was modulated in HCV core-expressing clones. We applied Nothern blot analysis to confirm 2 genes of which expression was downrgulated as well as 3 genes of which expression was upregulated in HCV core-expressing clones. We are currently analyzing the role of these genes in hepatocytes. We also investigated the effect of HCV core expression on apoptosis as well as cell proliferation. Expression of HCV core gene did not affect apoptosis, but significantly retarded proliferation of hepatocyte by inhibiting G1/S transition. These results suggest that infection of HCV inhibits hepatocyte proliferation but does not affect apoptosis of hepatocytes, raising the possibility that HCV-infected hepatocytes can be eradicated by apoptotic stimuli.
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[Publications] Ishida H, Ueda K, Ohkawa K, Kanazawa Y, Hosui A, Nakanishi F, Mita E, Kasahara A, Sasaki Y, Hori M, Hayashi N.: "Identification of multiple transcription factors, HLF, FTF, and E4BP4, controlling hepatitis B virus enhancer II."J Virol. 74. 1241-1251 (2000)
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[Publications] Kasahara A, Hayashi N, Mochizuki K, Hiramatsu N, Kato M,. Masuzawa M, Oshita M, Naito M, Kashiwagi T, Yoshihara H, Hori M, Kamada T: "Pretreatment viral load and response to interferon therapy for liver cirrhosis caused by hepatitis C virus : a multicenter controlled study."Hepatol Res. 16. 124-138 (2000)
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[Publications] Kasahara A, Hayashi N, Mochizuki K, Hiramatsu N, Sasaki Y, Kakumu S, Kiyosawa K, Okita K, Osaka Liver Disease Study Group.: "Clinical charactertistics of patients with chronic hepatitis C showing biochemical remission, without hepatitis C virus eradication, as a result of interferon therapy."J Viral Hep. 7. 343-351 (2000)
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[Publications] Tanaka Y, Sasaki Y, Katayama K, Hiramatsu N, Ito A, Murata H, Enomoto N, Oshita M, Mochizuki K, Ysujii M, Tsuji S, Kasahara A, Tomoda K, Nakamura H, Hayashi N, Hori M.: "Probability of hepatocellular carcinoma of small hepatocellular nodules undetectable by computed tomography during arterial portography."Hepatology. 31. 890-898 (2000)
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[Publications] Yuki N, Ishida H, Inoue T, Tabata T, Matsushita Y, Kishimoto H, Kato M, Masuzawa M, Sasaki Y, Hayashi N, Hori M.: "Reappraisal of biochemical hepatitis C activity in hemodialysis patients."J Clin Gastroenterol. 30. 187-194 (2000)
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[Publications] Yasuda K, Ohashi Y, Matsushima T, Kumada H, Hino K, Ito M, Takeuchi T, Kakumu S, Kuroki T, Hayashi N, Sata M, Iino S.: "Low-dose oral interferon-α in the treatment of chronic viral hepatitis type B : A double-blind, randomized, placebo-controlled, clinical trial."Curr Ther Res Clin Exp. 61. 245-254 (2000)
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[Publications] Tanaka H, Tsukuma H, Kasahara A, Hayashi N, Yoshihara H, Masuzawa M, Kanda T, Kashiwagi T, Inoue A, Kato M, Oshita A, Kinoshita Y, Kamada T.: "Effect of interferon therapy on the incidence of hepatocellular carcinoma and mortality of patients with chronic hepatitis C : A retrospective cohort study of 738 patients."Int J Cancer. 87. 741-749 (2000)
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[Publications] Horimoto M, Sasaki Y, Ugawa S, Wada S, Toyama T, Iyoda K, Yakushijin T, Minami Y, Ito T, Hijioka T, Eguchi A, Nakanishi M, Shimada S, Tohyama M, Hayashi N, Hori M.: "A novel strategy for cancer therapy by mutated mammalian degenerin gene transfer."Cancer Gene Ther. 7. 1341-1347 (2000)
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[Publications] Katayama K, Kasahara A, Sasaki Y, Kashiwagi T, Naito M, Masuzawa M, KatohM, Yoshihara H, Kamada T, Mukuda T, Hijioka T, Hori M, Hayashi N: "Immunological response to interferon-γ priming prior to interferon-α treatment in refractory chronic hepatitis C in relation to viral clearance."J Viral Hep. (in press).
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