Methylation status of ANAPC1, CDKN2A and TP53 promoter genes in individuals with gastric cancer

Gastric cancer is the forth most frequent malignancy and the second most common cause of cancer death worldwide. DNA methylation is the most studied epigenetic alteration, occurring through a methyl radical addition to the cytosine base adjacent to guanine. Many tumor genes are inactivated by DNA methylation in gastric cancer. We evaluated the DNA methylation status of ANAPC1, CDKN2A and TP53 by methylation-specific PCR in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosa in individuals from Northern Brazil. All gastric cancer samples were advanced stage adenocarcinomas. Gastric samples were surgically obtained at the João de Barros Barreto University Hospital, State of Pará, and were stored at -80°C before DNA extraction. Patients had never been submitted to chemotherapy or radiotherapy, nor did they have any other diagnosed cancer. None of the gastric cancer samples presented methylated DNA sequences for ANAPC1 and TP53. CDKN2A methylation was not detected in any normal gastric mucosa; however, the CDKN2A promoter was methylated in 30.4% of gastric cancer samples, with 35% methylation in diffuse-type and 26.9% in intestinal-type cancers. CDKN2A methylation was associated with the carcinogenesis process for ~30% diffuse-type and intestinal-type compared to non-neoplastic samples. Thus, ANAPC1 and TP53 methylation was probably not implicated in gastric carcinogenesis in our samples. CDKN2A can be implicated in the carcinogenesis process of only a subset of gastric neoplasias.

Gestão de orla urbana e turismo sustentável: reflexões e proposições a partir do projeto do complexo Ver-o-Rio em Belém (PA)

O trabalho tem por objetivo analisar como o turismo contribui para a gestão sustentável de orla urbana, discutindo as concepções e práticas de planejamento e gestão urbana na orla fluvial de Belém (PA), tendo como objeto empírico de pesquisa o Complexo Ver-O-Rio, espaço de lazer e turismo localizado na orla central da cidade. A análise foi realizada a partir do levantamento das diretrizes e instrumentos de planejamento e gestão urbanos das intervenções realizadas pela Prefeitura Municipal de Belém para o espaço orla. Além da temática apresentada o quadro conceitual aborda também estudos acerca do turismo, analisando seus aspectos como fenômeno social, utilizado neste debate como instrumento que contribui tanto para a gestão sustentável de orla urbana, quanto para mobilidade e inclusão da população local envolvida no processo, sob a perspectiva do turismo sustentável levantando dados e refletindo mais especificamente sobre os atores sociais envolvidos no Complexo Ver-O-Rio desde sua inauguração, como os comerciantes do entorno, os permissionários dos quiosques e os vendedores ambulantes que trabalham no espaço. O método utilizado foi um estudo de caso trabalhado através do tipo de abordagem qualitativa com análise do tipo histórico-descritiva. O estudo mostra que o turismo contribui para gestão sustentável de espaços situados em orlas urbanas na medida em que promove a mobilidade socioeconômica, a geração de emprego e renda e a participação da população local nesse processo.

Epigenetic alterations in human brain tumors in a Brazilian population

Aberrant methylation of CpG islands located in promoter regions represents one of the major mechanisms for silencing cancer-related genes in tumor cells. We determined the frequency of aberrant CpG island methylation for several tumor-associated genes: DAPK, MGMT, p14^ARF, p16^INK4a, TP73, RB1 and TIMP-3 in 55 brain tumors, consisting of 26 neuroepithelial tumors, 6 peripheral nerve tumors, 13 meningeal tumors and 10 metastatic brain tumors. Aberrant methylation of at least one of the seven genes studied was detected in 83.6% of the cases. The frequencies of aberrant methylation were: 40% for p14^ARF, 38.2% for MGMT, 30.9% for, p16^INK4a, 14.6% for TP73 and for TIMP-3, 12.7% for DAPK and 1.8% for RB1. These data suggest that the hypermethylation observed in the genes p14^ARF, MGMT and p16^INK4a is a very important event in the formation or progression of brain tumors, since the inactivation of these genes directly interferes with the cell cycle or DNA repair. The altered methylation rate of the other genes has already been reported to be related to tumorigenesis, but the low methylation rate of RB1 found in tumors in our sample is different from that so far reported in the literature, suggesting that perhaps hypermethylation of the promoter is not the main event in the inactivation of this gene. Our results suggest that hypermethylation of the promoter region is a very common event in nervous system tumors.