Elevated levels of plasma VEGF in patients with dengue hemorrhagic fever.

Vascular endothelial growth factor (VEGF) can be produced by monocytes and endothelial cells. It plays important role in angiogenesis and vascular permeability. The phenomenon of extensive plasma leakage into various serous cavities of the body is a cardinal symptom of dengue hemorrhagic fever (DHF). This study was performed to investigate the role of VEGF in patients with DHF. Plasma samples collected from the 53 dengue fever (DF) patients (including 14 patients with DHF), and 5 additional subjects with non-dengue febrile illness as controls were tested for VEGF levels using commercial enzyme-linked immunosorbent assay (ELISA) kits. The results showed that median plasma levels of VEGF in the patients with DHF (54.6 pg ml(-1)) were significantly higher than those of DF (14.6 pg ml(-1)) and control group (27.1 pg ml(-1)) (P<0.05). In addition, VEGF levels in DF patients were not significantly different from those of control patients with non-dengue febrile illness (P=0.17). Multiple regression analysis was used to analyze the clinical variables independently associated with VEGF levels. The data showed that D-dimer levels were significantly associated with VEGF levels. In this study, plasma VEGF levels in patients with DHF were significantly higher than values from DF patients. The association between increased plasma VEGF levels and increased plasma D-dimer levels in the patients with dengue illness suggests that activation of the fibrinolytic system may play a role in VEGF production in the patients with DF.

Clinical significance of plasma D-dimer levels and serum VEGF levels in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Angiogenesis and coagulation system activation are associated with tumor growth and metastasis. Vascular endothelial growth factor (VEGF) has been reported to play a major role in tumor angiogenesis. The elevation of plasma D-dimer level indicates the activation of coagulation and fibrinolysis. The purpose of this study was to: (a) evaluate the correlation between serum VEGF and plasma D-dimer level; (b) analyze the clinical features that might affect the VEGF and D-dimer levels in patients with hepatocellular carcinoma. METHODOLOGY: Twenty patients with hepatocellular carcinoma were included prior to treatment. Serum VEGF levels were measured by enzyme-linked immunosorbent assay. Plasma D-dimer levels were measured by quantitative latex microparticle enhanced turbidimetric immunoassay. RESULTS: The presence of a high plasma D-dimer level was found to be correlated with the presence of central necrosis, higher Child's grade, advanced TNM stage, and the presence of portal vein thrombosis when plasma D-dimer levels were compared between different clinicopathologic groups. Tumors larger than 2 cm in diameter had higher median serum VEGF levels than tumors less than 2cm in diameter. No correlation was found between plasma D-dimer level and serum VEGF level in hepatocellular carcinoma patients (r=0.126, p=0.598). CONCLUSIONS: No correlation was found between the plasma D-dimer level and the serum VEGF level in hepatocellular carcinoma patients. The plasma D-dimer level appeared to reflect the tumor stage and vascular invasion of hepatocellular carcinoma. Serum VEGF level in hepatocellular carcinoma patients showed a positive correlation with tumor size.

UDP-glucuronosyltransferase 1A7 genetic polymorphisms are associated with hepatocellular carcinoma risk and onset age.

OBJECTIVES: It has been demonstrated that the UDP-glucuronosyltransferase (UGT) 1A7*3 allele is a risk factor for hepatocellular carcinoma (HCC) in German and Japanese populations. In this study, therefore, we evaluated the association between UGT1A7 genetic polymorphisms and HCC risk in southern Taiwan, where hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are endemic. METHODS: The 217 HCC patients and 291 controls enrolled in this case-control study were genotyped for UGT1A7 polymorphisms using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Univariate logistic regression analysis revealed that presence of UGT1A7*2 and *3 alleles was associated with HCC risk [odds ratio (OR) = 1.50, 95% confidence interval (CI): 1.04 approximately 2.16 and OR = 1.73, 95% CI: 1.19 approximately 2.52, respectively]. Multiple logistic regression analysis demonstrated that significant independent risk factors for HCC were male gender (OR = 2.53, 95% CI: 1.42 approximately 4.52), HBV infection (OR = 13.73, 95% CI: 8.04 approximately 23.46), HCV infection (OR = 83.93, 95% CI: 37.01 approximately 190.32), and low-activity UGT1A7 genotype [high/low (H/L) genotype: OR = 1.93, 95% CI: 1.12 approximately 3.32; low/low (L/L) genotype: OR = 3.06, 95% CI: 1.50 approximately 6.24]. For male HCC patients, significantly earlier onset age was observed for those bearing the UGT1A7 low-activity genotype as opposed to those with the high-activity analogue (median age: 50 vs 59 yr; p < 0.05). CONCLUSIONS: An inverse dose-response relationship was demonstrated between the detoxifying activity of the UGT1A7 genotypes and HCC. Of the male HCC patients, median onset age for those carrying an UGT1A7 low-activity genotype was 9 yr lower than those bearing the high-activity variant.