Activating mechanism of transcriptor NF-kappaB regulated by hepatitis B virus X protein in hepatocellular carcinoma

AIM:To investigate the mechanism and significance of NF-κB activation regulated by hepatitis B virus X protein (HBx) in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).METHODS:The expression levels of HBx, p65,IκB-α and ubiquitin were detected by immunohistochemistry in HCC tissue microarrays (TMA) respectively, and IκB-α was detected by Western blot in HCC and corresponding liver tissues.RESULTS: The percentage of informative TMA samples was 98.8% in 186 cases with a total of 367 samples. Compared with corresponding liver tissues (60.0%),the HBx expression was obviously decreased in HBV-associated HCC (47.9%,u=2.24,P<0.05).On the contrary, the expressions of p65 (20.6% vs45.3%, u=4.85, P<0.01) and ubiquitin (8.9% vs 59.0%,u=9.68,P<0.01) were notably elevated in HCC.In addition, IκB-α had a tendency to go up. Importantly, positive relativity was observed between HBx and p65 (X^2=10.26,P<0.01), p65 and IκB-α (x^2=16.86,P<0.01), IκB-α and ubiquitin (x^2=8.90, P<0.01) in HCC, respectively.CONCLUSION:Both active and non-active forms of NF-κB are increased in HBV-associated HCC. Variant HBx is the major cause of the enhancement of NF-κB activity. The activation always proceeds in nucleus and the proteasome complexes play an important role in the activation.

Tumor cyclooxygenase-2 levels correlate with tumor invasiveness in human hepatocellular carcinoma

AIM: Recent studies suggested that cyclooxygenase-2(COX-2) enhances tumor angiogenesis via upregulationof vascular endothelial growth factor (VEGF). AlthoughCOX-2 expression has been demonstrated in hepatocellularcarcinoma (HCC), the significance of COX-2 in progressionof HCC remains unclear. This study evaluated the clinico-pathological correlation of COX-2 level and its relationshipwith VEGF level in HCC.METHODS: Fresh tumor tissues were obtained from 100patients who underwent resection of HCC. COX-2 proteinexpression was examined by immunohistochemistry, andquantitatively by an enzyme immunometric assay (EIA)of tumor cytosolic COX-2 levels. Tumor cytosolic VEGFlevels were measured by an ELISA.RESULTS: Immunostaining showed expression of COX-2in tumor cells. Tumor cytosolic COX-2 levels correlatedwith VEGF levels (r = 0.469, P＜0.001). Correlation withclinicopathological features showed significantly highertumor cytosolic COX-2 levels in the presence of multipletumors (P = 0.027), venous invasion (P = 0.030),microsatellite lesions (P = 0.037) and advanced tumorstage (P = 0.008). Higher tumor cytosolic COX-2 levelswere associated with worse patient survival.CONCLUSION: This study shows that elevated tumorCOX-2 levels correlate with elevated VEGF levels andinvasiveness in HCC, suggesting that COX-2 plays a significantrole in the progression of HCC.

Oncogenic role of clusterin overexpression in multistage colorectal tumorigenesis and progression

AIM: To investigate the expression pattern of clusterin in colorectal adenoma-carcinoma-metastasis series, and to explore the potential role of dusterin in multistage colorectal tumorigenesis and progression.METHOD:S: A colorectal carcinoma (CRC)-tissue microarray (TMA), which contained 85 advanced CRCs including 43 cases of Dukes B, 21 of Dukes C and 21 of Dukes D tumors, were used for assessing the expression of clusterin (clone 41D) and tumor cell apoptotic index (AI) by immunohistochemistry and TUNEL assay, respectively. Moreover the potential correlation of dusterin expression with the patient'sclinical-pathological features were also examined. RESULTS: The positive staining of clusterin in different colorectal tissues was primarily a cytoplasmic pattern. Cytoplasmic overexpression of clusterin was detected in none of the normal coloredal mucosa, 17% of the adenomas, 46% of the primary CRCs, and 57% of the CRC metastatic lesions. In addition, a significant positive correlation between overexpression of clusterin and advanced clinical (Dukes) stage was observed (P＜0.01). Overexpression of cytoplasmic clusterin in CRCs was inversely correlated with tumor apoptotic index (P＜0.01), indicating the anti apoptotic function of cytoplasmic clusterin in CRCs.CONCLUSION: These data suggests that overexpression of cytoplasmic dustin might be involved in the tumorigenesis and/or progression of CRCs. The anti-apoptotic function of cytoplasmic dusterin may be responsible, at least in part, for the development and biologically aggressive behavior of CRC.

Potent antitumoral effects of a novel gene-viral therapeutic system CNHK300-mEndostatin in hepatocellular carcinoma

Background The expression of therapeutic gene and its anti-tumor effects will be augmented and a synergism of oncolytic virus with the therapeutic gene is speculated. This study was undertaken to assess the anti-tumor effects of a novel gene-viral therapeutic system CNHK300-mEndostatin (CNHK300-mE) in hepatocellular carcinoma (HCC).