Detection of Helicobacter pylori in gastric biopsies, saliva and dental plaques of dyspeptic patients from Marília, São Paulo, Brazil: presence of vacA and cagA genes

Helicobacter pylori, a gram-negative bacterium, possesses two important virulence factors: the vacuolating toxin (vacA), and the cytotoxin-associated gene product (cagA). The aim of the present study was to evaluate the presence of H. pylori in the stomach and oral cavity of humans and compare the cagA and vacA genotypes of H. pylori found in different samples (stomach, saliva and dental plaque) from the same patient. Gastric biopsies, saliva and dental plaques were obtained from 62 dyspeptic adults. DNA was extracted and evaluated for the presence of H. pylori and the alleles cagA and vacA. Persons with gastritis had a higher frequency of H. pylori -positive samples in the stomach while positive samples from gastric biopsies were significantly correlated with those from the oral cavity. There was a high H. pylori frequency in patients while the cagA gene was associated with vacA s1 alleles in gastric biopsies. Our results suggest a reservoir of the species in the oral cavity and that, in one patient, more than one H. pylori strain may exist in the saliva, dental plaque and stomach. We found a relationship between gastric infection and the bacterium in the oral cavity, with the cytotoxin genotype varying between saliva and dental plaque.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Sacred Heart University Postgraduate Program in Oral BiologyMarília Medical School Blood Center Department of GeneticsMarília Medical School Department of Anatomic PathologyMarília Medical School Department of Digestive System SurgeryFederal University of São Paulo Department of MorphologyUNIFESP, Department of MorphologySciEL

Estudo dos genes ribossômicos e do efeito citogenético da 5-azacitidina na doença de Alzheimer

BV UNIFESP: Teses e dissertaçõe

Schizophrenia and fragile sites

Univ Fed Sao Paulo, Escola Paulista Med, Dept Morphol, Disciplina Genet, BR-04023900 Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Psiquiatria, BR-04023900 Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Morphol, Disciplina Genet, BR-04023900 Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Psiquiatria, BR-04023900 Sao Paulo, BrazilWeb of Scienc

Polymorphisms of the TP53 codon 72 and WRN codon 1367 in individuals from Northern Brazil with gastric adenocarcinoma

Gastric cancer is the second most frequent type of neoplasia and also the second most common cause of death in the world. TP53 codon 72, which produces variant proteins with an arginine (Arg) or proline (Pro), has been reported to be associated with cancers of the lung, oesophagus, stomach and cervix. Werner's syndrome (WS) is a premature ageing disease caused by a mutation in the WRN gene. the WRN protein acts as a DNA helicase and as an exonuclease. WRN codon 1367 produces variant proteins with an Arg or cysteine (Cys). This polymorphism has been studied, in order to understand the clinical impact of the molecular variants in WS and in age-related disorders. in the present study, the TP53 codon 72 and the WRN codon 1367 polymorphisms were investigated in 54 gastric adenocarcinoma patients (31 diffuse-type and 25 intestinal-type) and 54 controls. DNA samples were extracted, and PCR-RFLP was utilised for genotyping TP53 codon 72 and WRN codon 1367. the allele frequencies of the TP53 polymorphism were: Arg=0.74 and Pro=0.26. the allele frequencies of the WRN polymorphism were: Cys=0.73 and Arg=0.27. the crude genotypic frequencies in gastric cancer patients were similar to those of the controls, but in the WRN codon 1367 polymorphisms the mean age tended to be higher in the Arg/Arg genotypes. There also was an association, although not statistically significant, between the presence of Helicobacter pylori and the genotypes Cys/Cys and Cys/Arg and a higher percentage of cardia cancer among the Arg/Arg genotypes, and of non-cardia cancer among genotypes Cys/Cys and Cys/Arg. These findings may be a reflection of differences in the interaction between WRN codon 1367 polymorphisms and local factors in the stomach. To our knowledge, this is the first study to examine a genetic polymorphism of the WRN gene in cancer. the precise mechanisms of action of the TP53 and WRN polymorphisms involved in the aetiopathogeny of this disease need further investigation.Fed Univ Para, Ctr Ciencias Biol, Dept Biol, Lab Citogenet Humana, BR-66075900 Belem, Para, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Disciplina Genet, São Paulo, BrazilFac Med Marilia, Disciplinas Genet & Biol Mol, Marilia, SP, BrazilUniv São Paulo, Fac Med Ribeirao Preto, Dept Genet, Ribeirao Preto, SP, BrazilHosp Univ Joao de Barros Barreto, Serv Cirurgia, UFPA, Belem, Para, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Disciplina Genet, São Paulo, BrazilWeb of Scienc

Differential expression of histone deacetylase and acetyltransferase genes in gastric cancer and their modulation by trichostatin A

Gastric cancer is still the second leading cause of cancer-related death worldwide, even though its incidence and mortality have declined over the recent few decades. Epigenetic control using histone deacetylase inhibitors, such as trichostatin A (TSA), is a promising cancer therapy. This study aimed to assess the messenger RNA (mRNA) levels of three histone deacetylases (HDAC1, HDAC2, and HDAC3), two histone acetyltransferases (GCN5 and PCAF), and two possible targets of these histone modifiers (MYC and CDKN1A) in 50 matched pairs of gastric tumors and corresponding adjacent nontumors samples from patients with gastric adenocarcinoma, as well as their correlations and their possible associations with clinicopathological features. Additionally, we evaluated whether these genes are sensitive to TSA in gastric cancer cell lines. Our results demonstrated downregulation of HDAC1, PCAF, and CDKN1A in gastric tumors compared with adjacent nontumors (P < 0.05). On the other hand, upregulation of HDAC2, GCN5, and MYC was observed in gastric tumors compared with adjacent nontumors (P < 0.05). the mRNA level of MYC was correlated to HDAC3 and GCN5 (P < 0.05), whereas CDKN1A was correlated to HDAC1 and GCN5 (P < 0.05 and P < 0.01, respectively). in addition, the reduced expression of PCAF was associated with intestinal-type gastric cancer (P = 0.03) and TNM stages I/II (P = 0.01). the increased expression of GCN5 was associated with advanced stage gastric cancer (P = 0.02) and tumor invasion (P = 0.03). the gastric cell lines treated with TSA showed different patterns of histone deacetylase and acetyltransferase mRNA expression, downregulation of MYC, and upregulation of CDKN1A. Our findings suggest that alteration of histone modifier genes play an important role in gastric carcinogenesis, contributing to MYC and CDKN1A deregulation. in addition, all genes studied here are modulated by TSA, although this modulation appears to be dependent of the genetic background of the cell line.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Disciplina Genet, Dept Morfol & Genet, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ortopedia & Traumatol, BR-04038032 São Paulo, BrazilUniv Sagrado Coracao, BR-17011160 Bauru, BrazilFac Med Marilia, Dept Genet & Biol Mol, Hemoctr, BR-17519050 Marilia, BrazilFed Univ Para, Nucleo Pesquisa Oncol, Hosp Joao de Barros Barreto, BR-66073000 Belem, Para, BrazilUniversidade Federal de São Paulo, Disciplina Gastroenterol Cirurg, Dept Cirurgia, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Patol, BR-04023000 São Paulo, BrazilFed Univ Para, Lab Citogenet Humana, Inst Ciencias Biol, BR-66075110 Belem, Para, BrazilUniversidade Federal de São Paulo, Disciplina Genet, Dept Morfol & Genet, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ortopedia & Traumatol, BR-04038032 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Gastroenterol Cirurg, Dept Cirurgia, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Patol, BR-04023000 São Paulo, BrazilWeb of Scienc