Methylation pattern of THBS1, GATA-4, and HIC1 in pediatric and adult patients infected with helicobacter pylori

Background: Helicobacter pylori infection is usually acquired in childhood and persists into adulthood if untreated. The bacterium induces a chronic inflammatory response, which is associated with epigenetic alterations in oncogenes, tumor-suppressor genes, cell-cycle regulators, and cell-adhesion molecules. Aim: The aim of this study was to analyze the effect of H. pylori infection on the methylation status of Thrombospondin-1 (THBS1), Hypermethylated in cancer 1 (HIC1) and Gata binding protein-4 (GATA-4) in gastric biopsy samples from children and adults infected or uninfected with the bacterium and in samples obtained from gastric cancer patients. Methods: The methylation pattern was analyzed with methylation-specific PCR. Results: Our results showed that H. pylori infection was associated with methylation of the promoter regions of the THBS1 and GATA-4 genes in pediatric and adult samples (p < 0.01). HIC1 showed the lowest level of methylation, which was not an early event during gastric carcinogenesis. Conclusions: The results from this study indicate that methylation of THBS1 and GATA-4 occurs in the early stages of chronic gastritis and gastric cancer in association with H. pylori infection; however, in gastric cancer samples, other mechanisms cooperate with the down-regulation of these genes. Methylation of HIC1 may not be the principal mechanism implicated in its down-regulation in gastric cancer samples. © 2013 Springer Science+Business Media New York.

Detecção de mutação no gene supressor de tumor p53 e associação e cepas patogênicas do Helicobacter pylori em câncer gástrico

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Metabolismo de glicogênio e relógio biológico em Neurospora crassa: fatores e cofatores de transcrição envolvidos nos processos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Caracterização funcional de fatores de transcrição hipotéticos de Neurospora crassa

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo do Fator de Início de Tradução de Eucariotos 5A (eIF5A) na tradução específica e na ligação direta com ribossomo

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

TGFβ, pSmad2, p53, p63, E-caderina e Vimentina como marcadores prognósticos em tumores espontâneos de mama de cadelas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Verificação da formação de complexos protéicos nos telômeros de L. amazonensis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Avaliação imuno-histoquímica do marcado de proliferação celular KI-67 em glandula perianal normal e em neoplástica de cães

Pós-graduação em Ciência Animal - FMVA

Genotipagem de HPV e imunorreatividade da ciclina D1 em adenocarcinoma de colo do útero

Pós-graduação em Patologia - FMB

Caracterização funcional de eIF5A: análise genética e molecular utilizando o modelo de Saccharomyces cerevisiae

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Expressão da survivina em diferentes condições relacionadas à carcinogênese intra-bucal humana

Pós-graduação em Biopatologia Bucal - ICT

Estudos imuno-histoquímico das proteínas p53, p16, Fhit, caspase 3 e antígeno Ki67 ; e citogenético molecular em lesões benignas e carcinoma de esôfago

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Expressão de genes relacionados ao ciclo celular e proteção da mucosa gástrica em metaplasia intestinal e ulcera gástrica em comparação com câncer gástrico

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Mutagenicity of hydroxyurea in lymphocytes from patients with sickle cell disease

Hydroxyurea is commonly used in the treatment of myeloproliferative diseases and in patients with sickle cell disease (SCD). The use of this antineoplastic agent in patients with SCD is justified because of the drug's ability to increase fetal hemoglobin levels, thereby decreasing the severity of SCD. However, high doses or prolonged treatment with hydroxyurea can be cytotoxic or genotoxic for these patients, with an increased risk of developing acute leukemia. This danger can be avoided by monitoring the lymphocytes of patients treated with hydroxyurea. Cytogenetic tests are important endpoints for monitoring the physiological effects of physical and chemical agents, including drugs. In this work, we assessed the genotoxicity of hydroxyurea in short-term cultures of lymphocytes from SCD patients. Hydroxyurea was not cytotoxic or genotoxic at the concentrations tested in the G2 phase of the cell cycle. These results support the use of hydroxyurea in the treatment of SCD, although further work is necessary to understand the effects of this drug in vivo

Conventional cytogenetic characterization of a new cell line, ACP01, established from a primary human gastric tumor

Gastric cancer is the second most frequent type of neoplasia and also the second most important cause of death in the world. Virtually all the established cell lines of gastric neoplasia were developed in Asian countries, and western countries have contributed very little to this area. In the present study we describe the establishment of the cell line ACP01 and characterize it cytogenetically by means of in vitro immortalization. Cells were transformed from an intestinal-type gastric adenocarcinoma (T4N2M0) originating from a 48-year-old male patient.This is the first gastric denocarcinoma cell line established in Brazil. The most powerful application of the cell line ACP01 is in the assessment of cytotoxicity. Solid tumor cell lines from different origins have been treated with several conventional and investigational anticancer drugs. The ACP01 cell line is triploid, grows as a single, non-organized layer, similar to fibroblasts, with focus formation,heterogeneous division, and a cell cycle of approximately 40 h. Chromosome 8 trisomy, present in 60% of the cells, was the most frequent cytogenetic alteration. These data lead us to propose a multifactorial triggering of gastric cancer which evolves over multiple stages involving progressive genetic changes and clonal expansion.