RESUMEN
OBJECTIVE: To identify the association strength of the prevalence of HBeAg, covalently closed circular DNA (cccDNA) and 1762/1764 nucleotide mutations of hepatitis B virus (HBV) with the occurrence of hepatocellular carcinoma (HCC) in Qidong high risk male cohort. METHODS: A cohort of 377 middle aged HBV infected men in Qidong was followed from January 1989 to December 2002. Incident HCC cases were carefully registered. A matched case-controlled study was conducted on 32 pairs of inherent HCC cases with their matched non-HCC controls. Serum HBeAg was measured by ELISA. cccDNA was detected by primer selected PCR. 1762/1764 nucleotide mutations of HBV was identified by PCR of X gene segment spanning the mutation region. Standard statistical comparison between the prevalence of each HBV marker in HCC versus in control group provided the odds ratio with P value to evaluate its association strength with HCC occurrence. RESULTS: Serum HBeAg prevalence was 53.1% (17/32) in HCC group versus and 15.6% (5/32) in controls (OR = 6.12, P < 0.01). Prevalence of serum cccDNA was detected in 62.5% (21/32) of HCC cases but in 25.0% (8/32) of controls (OR = 5.73, P < 0.01). Sequence of detected cccDNA was repeatedly found to be over 90% homologous with HBV. However, the mutation rate of nucleotide 1762/1764 was not found to be statistically higher in the HCC group versus its controls (OR = 1.54, P = 0.425). CONCLUSIONS: The Qidong male case-controlled cohort had shown that serum HBeAg and cccDNA prevalence were tightly associated with hepatocellular carcinoma occurrence in HBV infected men. These biomarkers may have predictive value in earlier diagnosis and therapeutic effect monitoring.
Asunto(s)
Carcinoma Hepatocelular/virología , Virus de la Hepatitis B/genética , Hepatitis B Crónica/virología , Neoplasias Hepáticas/virología , Carcinoma Hepatocelular/etiología , Estudios de Casos y Controles , Estudios de Cohortes , ADN Viral/sangre , ADN Viral/genética , Estudios de Seguimiento , Antígenos e de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/genética , Hepatitis B Crónica/complicaciones , Humanos , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Mutación Puntual , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common cancer in China. Hepatitis B and C viruses (HBV and HCV) and aflatoxins are known risk factors for HCC, but the etiological status of these factors in HCC development is not clear. This study was undertaken to define the absolute importance of HBV in hepatocarcinogenesis of North China. METHODS: A consecutive series of 119 patients with pathologically proven HCC were collected from North China during January 1998 to December 2000 by the Cancer Hospital of the Chinese Academy of Medical Sciences, Beijing. Serum HBsAg, anti-HBc and anti-HCV were negative HBV sero-markers. The HBV X gene was analyzed for its expression by PCR, DNA sequencing, and immunohistochemistry. RESULTS: In the 119 HCC patients, 82.4% (98/119) were HBsAg seropositive. When a comprehensive set of HBV markers were detected, the HBV infection rate in these HCC patients was 99.2% (118/119). Of the patients, 11.8%(14/119) were found to be anti-HCV positive. But all the anti-HCV positive HCC patients were co-infected with HBV. CONCLUSIONS: HBV infection is virtually ubiquitous in HCC patients in North China. The tight association of HBV with HCC strongly suggests the dominant role of HBV infection in causing hepatocellular carcinoma. About 11.8% of HCC patients being HCV-related are co-infected with HBV.
Asunto(s)
Carcinoma Hepatocelular/epidemiología , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B Crónica/epidemiología , Neoplasias Hepáticas/epidemiología , Adulto , Distribución por Edad , Anciano , Carcinoma Hepatocelular/diagnóstico , China/epidemiología , Comorbilidad , ADN Viral/análisis , Femenino , Hepatitis B Crónica/diagnóstico , Humanos , Incidencia , Neoplasias Hepáticas/diagnóstico , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Pronóstico , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo , Distribución por Sexo , Tasa de SupervivenciaRESUMEN
This is the first report that a Fusarium toxin nivalenol (NIV) naturally existing at high levels in dietary food in high-risk areas of cancer of esophagus and gastric cardia in China induced benign and malignant tumors in mice. The levels of two Fusarium toxins, nivalenol and deoxynivalenol (DON) were quantitated using high performance liquid chromatography (HPLC) in a total of 97 samples of dietary wheat flour, barley and corn collected from families in two areas with high mortality rate of cancer of esophagus and gastric cardia (132/100,000), Linxian, Henan province and Cixiang, Hepei province, China. The mean level of NIV and DON in three dietary foods was 830+/-927 microg/kg (range 584-1,780 microg/kg) and 4,281+/-6,114 microg/kg (range 732-10,980 microg/kg) respectively. The highest mean level of NIV was 1,780+/-1,705 microg/kg found in barley from Linxian, that of DON was 10,980+/-10,139 microg/kg found in corn from Cixiang. NIV was undetectable in 2 samples of rice from USA. The mean levels of NIV in three main dietary foods in those two high-risk areas were estimated at 400 to 800-fold higher than that in the USA, where NIV was undetectable in dietary food, and the mortality rate of esophageal cancer is <5/100,000 in white Caucasians in the USA, (odds ratio was estimated at 17-34, p<0.000005). These data suggest that Linxian and Cixiang peasants who consumed a diet with high NIV had significantly higher risk for developing esophageal cancer than the US residents who consumed food without or with negligible amounts of NIV. Three repeated experiments were performed using Balb/C mice with inter-mittent application of NIV, alternate with 12-Tetradeconoyl-phorbol-13-acetate (TPA) application on skin. Papillomas and carcinomas developed in a total of 23/49 (47%) mice that survived 11-60 weeks of experiments. Among all the tumors, 4 carcinomas in 3 mice were identified. No tumors were found in the 60 control mice applying either TPA or acetone (solvent) only on skin.
Asunto(s)
Cardias/patología , Dieta , Neoplasias Esofágicas/inducido químicamente , Fusarium/metabolismo , Neoplasias Experimentales/inducido químicamente , Neoplasias Gástricas/inducido químicamente , Tricotecenos/farmacología , Alimentación Animal , Animales , Carcinoma , Cromatografía Líquida de Alta Presión , Aberraciones Cromosómicas , Femenino , Harina , Hordeum/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Micotoxinas/química , Oportunidad Relativa , Papiloma , Temperatura , Zea mays/metabolismoRESUMEN
OBJECTIVE: To study the inhibitory effect of RNA interference (RNAi) on c-myc expression in hepatocellular carcinoma cell line, HepG2. METHODS: Expression vector of c-myc gene-targeting small interference RNA (siRNA) was constructed (psilencer-c-myc) and transfected into HepG2 cells by lipofectamine, and the unloaded vector was used as control (mock). The expression of c-myc mRNA and protein was identified by quantitive PCR and Western blot. Apoptosis of the transfected cells was examined by flow cytometry and immunofluorescent microscopy. RESULTS: After HepG2 cells were transfected with psilencer-c-myc, the expression of c-myc mRNA and protein was suppressed with an inhibition rate of 67% compared with the mock-transfected cells. Apoptosis was identified in the transfected HepG2 cells. CONCLUSION: The expression of c-myc at transcriptional and translational levels in HepG2 cells transfected with siRNA is markedly inhibited, which may be associated with the induction of apoptosis.