Abstract. Liver cancer is the sixth most commonly occurring cancer globally, and the main histological type is hepatocellular carcinoma. This type of neoplasia has a poor prognosis due to a high rate of recurrence and intrahepatic metastasis, which are closely are closely associated with the angiogenic process. Vascular endothelial growth factor (VEGF), which is under the control of hypoxia inducible factor-1α (HIF-1α), stimulates the proliferation of endothelial cells and increases cell permeability, promoting the growth, spread and metastasis of tumors. Melatonin, the main hormone secreted by the pineal gland, may have a significant role in tumor suppression and has demonstrated antiangiogenic and antimetastatic effects. The aim of the present study was to analyze the cell viability, migration and invasion, as well as the expression of proangiogenic proteins VEGF and HIF-1α, in HepG2 hepatocarcinoma cells, following treatment with melatonin. Cells were cultured and cell viability was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of proangiogenic proteins VEGF and HIF-1α, under conditions of normoxia and hypoxia, was verified using immunocytochemistry and quantified by densitometry. The analysis of the processes of cell migration and invasion was performed in a Boyden chamber. The MTT assay revealed a reduction in cell viability (P=0.018) following treatment with 1 mM melatonin for 24 h. The expression of proangiogenic proteins VEGF and HIF-1α was reduced in cells treated with 1 mM melatonin for 24 h in normoxic (P<0.001) and hypoxic (P<0.001) conditions, compared with the control group and with induced hypoxia alone. The rate of cell migration and invasion was additionally reduced in cells treated with 1 mM melatonin for 48 h when compared with the control group (P=0.496). The results of the present study suggest that melatonin may have an antiproliferative, antiangiogenic and antimetastatic role in hepatocarcinoma cells and may present a novel therapeutic option for the treatment of liver cancer.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.

ResumoO presente estudo trata do diagnóstico da influência do crescimento urbano na área da sub-bacia hidrográfica do rio Vargem Grande em Montes Claros-MG e os impactos ambientais que esse crescimento causa nos recursos hídricos. As análises feitas revelaram que o rápido crescimento da mancha urbano tem proporcionado o comprometimento da quantidade e qualidade da água dessa sub-bacia através de atividades antrópicas realizadas no local como: loteamentos urbanos, retirada da vegetação natural além de lançamento de resíduos sólidos nos cursos d'água ou próximo a eles.Palavras-chave:Recursos Hídricos, Crescimento Urbano, Impactos Ambientais. AbstractThis study deals with the diagnosis of the influence of urban growth in the area of the sub-basin of the river Vargem Grande Claros -MG Montes and environmental impacts that this growth because water resources. The analyzes revealed that the rapid growth of urban spot has provided the commitment of the quantity and quality of water in this sub -basin through anthropogenic activities on site as urban settlements , removal of natural vegetation as well as release of solid waste in watercourses ' water or close to them.

AIMTo evaluated the association of the risk factors and polymorphisms in MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G genes.METHODSPatients with cirrhosis (n = 116), hepatocellular carcinoma (HCC) (n = 71) and controls (n = 356) were included. Polymerase chain reaction followed by enzymatic digestion and allelic discrimination technique real-time PCR techniques were used for analysis. MINITAB-14.0 and SNPstats were utilized for statistical analysis.RESULTSShowed that age ≥ 46 years (OR = 10.31; 95%CI: 5.66-18.76; P < 0.001) and smoking (OR = 0.47; 95%CI: 0.28-0.78; P = 0.003) were associated with cirrhosis. Age ≥ 46 years (OR = 16.36; 95%CI: 6.68-40.05; P < 0.001) and alcohol habit (OR = 2.01; 95%CI: 1.03-3.89; P = 0.039) were associated with HCC. MTHFR A1298C in codominant model (OR = 3.37; 95%CI: 1.52-7.50; P = 0.014), recessive model (OR = 3.04; 95%CI: 1.43-6.47; P = 0.0051) and additive model (OR = 1.71; 95%CI: 1.16-2.52; P = 0.0072) was associated with HCC, as well as MTR A2756G in the additive model (OR = 1.68; 95%CI: 1.01-2.77; P = 0.047), and MTRR A66G in the codominant model (OR = 3.26; 95%CI: 1.54-6.87; P < 0.001), dominant model (OR = 2.55; 95%CI: 1.24-5.25; P = 0.007) and overdominant model (OR = 3.05; 95%CI: 1.66-5.62; P < 0.001). MTR A2756G in the additive model (OR = 1.54; 95%CI: 1.02-2.33; P = 0.042) and smokers who presented at least one polymorphic allele for MTRR A66G (OR = 1.71; 95%CI: 0.77-3.82; P = 0.0051) showed increased risk for cirrhosis. There was no association between clinical parameters and polymorphisms.CONCLUSIONAge ≥ 46 years, alcohol habit and MTR A2756G, MTHFR A1298C and MTRR A66G polymorphisms are associated with an increased risk of HCC development; age ≥ 46 years, tobacco habit and the MTR A2756G polymorphism are associated with cirrhosis.

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