Influence of vascular endothelial growth factor and alpha-fetoprotein on hepatocellular carcinoma.

We evaluated the influence of the vascular endothelial growth factor (VEGF) -C936T polymorphism on prognosis of hepatocellular carcinoma (HCC), cirrhosis, and hepatitis C virus (HCV) infection. Serum VEGF and alpha-fetoprotein (AFP) levels were determined and used to characterize sensitivity and specificity. A total of 285 subjects were studied: 68 HCC, 118 cirrhosis, 43 HCV, and 56 healthy controls. Prevalence of the VEGF -C936T polymorphism and serum levels of VEGF and AFP were analyzed by polymerase chain reaction-restriction fragment length polymorphism and enzyme-linked immunosorbent assay, respectively. The genotype CC (frequencies between 63.24 and 76.79%; P > 0.05) and the C allele (absolute frequencies from 0.816 to 0.884, P > 0.05) were prevalent in all groups. Higher VEGF levels in HCC patients (588.0 ± 501.0 pg/mL) were observed, particularly in patients with the T allele in VEGF -C936T (764.4 ± 571.7 pg/mL) compared to those in the other groups (P < 0.05). The same trend occurred with AFP levels (HCC = 8.522 ± 23.830; cirrhosis = 12.7 ± 59.3; HCV = 4.6 ± 4.7; control = 2.7 ± 1.8 ng/mL; P = 0.005). Levels of VEGF and AFP showed sensitivity of 65 and 28% and specificity of 85 and 99%, respectively, for HCC patients. In conclusion, the VEGF -C936T polymorphism is not associated with HCC but the mutant allele (T) increases VEGF levels in HCC patients. VEGF could be a potential biomarker for HCC, while AFP could be used to distinguish between patients with HCC and cirrhosis or HCV.

Nicotine induces sensitization of turning behavior in 6-hydroxydopamine lesioned rats.

Nicotinic drugs have been proposed as putative drugs to treat Parkinson's disease (PD). In this study, we investigated whether nicotine can sensitize parkinsonian animals to the effect of dopaminergic drugs. Testing this hypothesis is important because nicotine has been shown to present neuroprotective and acute symptomatic effects on PD, but few studies have addressed the question of whether it may induce long-lasting effects on dopamine neurotransmission. We tested this hypothesis in the 6-hydroxydopamine (6-OHDA) rat model of PD. A pretreatment of these rats with 0.1-1.0 mg/kg nicotine induced a dose-dependent sensitization of the turning behavior when the animals were challenged with the dopamine receptor agonist apomorphine 24 h later. In agreement with previous studies, while apomorphine induced contraversive turns, nicotine, as well as amphetamine, induced ipsiversive turns in the 6-OHDA rats. This result suggests that, like amphetamine, nicotine induces turning behavior by promoting release of dopamine in the non-lesioned striatum of the rats. However, it is unlikely that the release of dopamine may also explain the nicotine-induced sensitization of turning behavior. First, the dopamine amount that could be released in the lesioned hemi-striatum by the nicotine pretreatment was minimum-less than 3%, as detected by HPLC-EC. Second, a pretreatment with amphetamine did not induce this behavioral sensitization. A pretreatment with apomorphine-induced sensitization, but it was minimal when compared to that induced by nicotine. Therefore, it is unlikely that the sensitization of the turning behavior induced by nicotine was consequent of the release of dopamine. However, the expression of such sensitization seems to depend on the activation of dopaminergic receptors, since it was seen when the nicotine-sensitized animals were challenged with apomorphine, but not with a second nicotine challenge. These findings are relevant for PD drug therapy since they suggest that the doses of dopaminergic drugs used to treat PD could be reduced if a nicotinic drug were co-administered.