start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=20111021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Hepatitis B virus core promoter mutations G1613A and C1653T are significantly associated with hepatocellular carcinoma in genotype C HBV-infected patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Hepatitis B virus (HBV) is a major cause of hepatocarcinogenesis. To identify mutations relevant to hepatocellular carcinoma (HCC) development, we compared the full genome sequences of HBV from the sera of patients with and without HCC. Methods: We compared the full genome sequences of HBV isolates from 37 HCC patients (HCC group 1) and 38 patients without HCC (non-HCC group 1). We also investigated part of the core promoter region sequences from 40 HCC patients (HCC group 2) and 68 patients without HCC. Of the 68 patients who initially did not have HCC, 52 patients remained HCC-free during the follow-up period (non-HCC group 2), and 16 patients eventually developed HCC (pre-HCC group 2). Serum samples collected from patients were subjected to PCR, and the HBV DNA was directly sequenced. Results: All patients had genotype C. A comparison of the nucleotide sequences of the HBV genome between HCC group 1 and non-HCC group 1 revealed that the prevalence of G1613A and C1653T mutations in the core promoter region was significantly higher in the HCC group. These mutations tended to occur simultaneously in HCC patients. Multivariate analysis with group 2 revealed that the presence of HCC was associated with aging and the double mutation. Future emergence of HCC was associated with aging and the presence of a single G1613A mutation. Conclusions: G1613A and C1653T double mutations were frequently found in patients with HCC. A single G1613A mutation was associated with future emergence of HCC. These mutations may serve as useful markers in predicting HCC development. en-copyright= kn-copyright= en-aut-name=TatsukawaMasashi en-aut-sei=Tatsukawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakakiAkinobu en-aut-sei=Takaki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShirahaHidenori en-aut-sei=Shiraha en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KoikeKazuko en-aut-sei=Koike en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwasakiYoshiaki en-aut-sei=Iwasaki en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobashiHaruhiko en-aut-sei=Kobashi en-aut-mei=Haruhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiokaShin-Ichi en-aut-sei=Fujioka en-aut-mei=Shin-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SakaguchiKohsaku en-aut-sei=Sakaguchi en-aut-mei=Kohsaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoKazuhide en-aut-sei=Yamamoto en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=2 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=3 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=4 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=5 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=6 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=7 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=8 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=9 en-affil= kn-affil=Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=20110104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Runt-related transcription factor 3 (RUNX3) is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC). Methods: RUNX3 expression was analyzed by immunoblot and immunohistochemistry in HCC cells and tissues, respectively. Hep3B cells, lacking endogenous RUNX3, were introduced with RUNX3 constructs. Cell proliferation was measured using the MTT assay and apoptosis was evaluated using DAPI staining. Apoptosis signaling was assessed by immunoblot analysis. Results: RUNX3 protein expression was frequently inactivated in the HCC cell lines (91%) and tissues (90%). RUNX3 expression inhibited 90 +/- 8% of cell growth at 72 h in serum starved Hep3B cells. Forty-eight hour serum starvation-induced apoptosis and the percentage of apoptotic cells reached 31 +/- 4% and 4 +/- 1% in RUNX3-expressing Hep3B and control cells, respectively. Apoptotic activity was increased by Bim expression and caspase-3 and caspase-9 activation. Conclusion: RUNX3 expression enhanced serum starvation-induced apoptosis in HCC cell lines. RUNX3 is deleted or weakly expressed in HCC, which leads to tumorigenesis by escaping apoptosis. en-copyright= kn-copyright= en-aut-name=NakanishiYutaka en-aut-sei=Nakanishi en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShirahaHidenori en-aut-sei=Shiraha en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishinaShin-ichi en-aut-sei=Nishina en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaShigetomi en-aut-sei=Tanaka en-aut-mei=Shigetomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsubaraMinoru en-aut-sei=Matsubara en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakaokaNobuyuki en-aut-sei=Takaoka en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UemuraMasayuki en-aut-sei=Uemura en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KuwakiKenji en-aut-sei=Kuwaki en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HagiharaHiroaki en-aut-sei=Hagihara en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ToshimoriJunichi en-aut-sei=Toshimori en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OhnishiHideki en-aut-sei=Ohnishi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TakakiAkinobu en-aut-sei=Takaki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakamuraShinichiro en-aut-sei=Nakamura en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KobayashiYoshiyuki en-aut-sei=Kobayashi en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=NousoKazuhiro en-aut-sei=Nouso en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YagiTakahito en-aut-sei=Yagi en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamamotoKazuhide en-aut-sei=Yamamoto en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ affil-num=2 en-affil= kn-affil=Okayama Univ affil-num=3 en-affil= kn-affil=Okayama Univ affil-num=4 en-affil= kn-affil=Okayama Univ affil-num=5 en-affil= kn-affil=Okayama Univ affil-num=6 en-affil= kn-affil=Okayama Univ affil-num=7 en-affil= kn-affil=Okayama Univ affil-num=8 en-affil= kn-affil=Okayama Univ affil-num=9 en-affil= kn-affil=Okayama Univ affil-num=10 en-affil= kn-affil=Okayama Univ affil-num=11 en-affil= kn-affil=Okayama Univ affil-num=12 en-affil= kn-affil=Okayama Univ affil-num=13 en-affil= kn-affil=Okayama Univ affil-num=14 en-affil= kn-affil=Okayama Univ affil-num=15 en-affil= kn-affil=Okayama Univ affil-num=16 en-affil= kn-affil=Okayama Univ affil-num=17 en-affil= kn-affil=Okayama Univ affil-num=18 en-affil= kn-affil=Okayama Univ affil-num=19 en-affil= kn-affil=Okayama Univ END