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Objective: To investigate the dynamic expressions of TGF-beta 1 and TGF-beta 1 mRNA at different stages of hepatocellular carcinoma (HCC) development and their use in clinical diagnosis., Methods: Hepatoma models were developed with 2-FAA using male Sprague-Dawley (SD) rats. Morphological changes of the rat liver histological preparations (H and E stained) were studied. The fragment of TGF-beta 1 gene obtained was amplified by nested RT-PCR. Dynamic change of TGF-beta 1 level was quantitatively analyzed by ELISA. The distribution of TGF-beta 1 in the cells and its gene expression were detected in human HCC tissues., Results: The progressive increases of hepatic TGF-beta 1 and TGF-beta 1 mRNA were observed in rat hepatocytes which progressed from granular degeneration, atypical hyperplasia and finally to HCC development induced by 2-FAA. The expression levels in HCC tissues were significantly higher than those in the normal and degenerative ones. TGF-beta 1 was shown in rat hepatocytes by immunohistochemistry. Plasma TGF-beta 1 was detected in 89.5% of all the patients with HCC, but it was detected in 93.3% of them who had an AFP less than 400 microg/L. TGF-beta 1 mRNA showed a stronger expression in HCC tissues. TGF-beta 1 mRNA was found in peripheral blood mononuclear cells from all HCC patients with extrahepatic metastasis., Conclusion: TGF-beta 1 may participate in hepatocyte canceration. The overexpression of TGF-beta 1 and TGF-beta 1 mRNA could be useful markers for early diagnosis and predicting prognosis of HCC.

Objective: To study the resistant rate of hepatitis B virus (HBV) to ADV and the dynamic evolution of HBV in lamivudine (Lam)-resistant chronic hepatitis B (CHB) patients., Methods: Twenty-three Lam-resistant CHB patients were assigned to a 10mg/d ADV monotherapy for 68-116 weeks. The baseline and different time point blood samples after ADV monotherapy were analyzed for ADV-resistant mutations using direct sequencing of PCR products; the evolution of HBV mutations was examined by clonal analysis of serial samples from one patient infected with ADV-associated resistant HBV strains., Results: The cumulative incidence of genotypic ADV resistance at weeks 48 and 96 was 4.3% and 10.5% respectively respectively. The evolution analysis of HBV mutant strains in an ADV-resistant CHB patient showed that the proportion of YMDD mutants gradually decreased with rtA181S mutants increasing over time after ADV monotherapy, and that rtA181S+N236T mutants became the predominant strains during prolonged ADV monotherapy. The addition of Lam to the ongoing ADV treatment had poorer antiviral response in the patient with rtA181S or rtA181S+N236T mutant infection; one clone with multi-drug resistant mutations was selected during Lam and ADV combination therapy., Conclusion: Increased risk of adefovir resistance and selection of multi-drug resistant mutations are associated with long-term ADV monotherapy in patients with Lam-resistant chronic hepatitis B.

Objective: To explore the roles of vascular endothelial growth factor (VEGF) in microvessel angiogenesis, development and metastasis of hepatocellular carcinoma (HCC)., Methods: The cellular distributions of VEGF expression and microvascular density (MVD) in 36 HCCs were investigated, and the levels of total RNA and VEGF were detected in HCCs, Para cancerous, and distal cancerous tissues, respectively., Results: The incidence of VEGF was 63.9% in 36 cases of HCCs, 78.3% in non-encapsulated HCCs, and 90.9% in HCCs with extrahepatic metastasis, respectively. The VEGF expression was tightly correlated with MVD (t=4.49, P<0.01). No significant difference was found between VEGF or MVD and tumor diameter or differentiation degree. The level of total RNA in HCCs was lower but the VEGF level significantly higher than those of Para cancerous or distal cancerous ones (q=6.10, P<0.01)., Conclusion: The present data suggest that VEGF over expression and MVD abnormality are useful markers for vascular invasion and metastasis of liver tumors.