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

Prohibitin Expression Deregulation in Gastric Cancer Is Associated with the 3 ' Untranslated Region 1630 C > T Polymorphism and Copy Number Variation

PHB is a reported oncogene and tumor suppressor in gastric cancer. Here, we evaluated whether the PHB copy number and the rs6917 polymorphism affect its expression in gastric cancer. Down-regulation and up-regulation of PHB were observed in the evaluated tumors. Reduced expression was associated with tumor dedifferentiation and cancer initiation. the T allele of the rs6917 polymorphism was associated with reduced PHB mRNA levels. Moreover, the up-regulation of PHB appeared to be regulated by the gain of additional gene copies. Thus, PHB copy number variation and differential expression of the rs6917 polymorphism may play a role in PHB transcriptional regulation.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Disciplina Genet, Dept Morfol & Genet, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ortopedia & Traumatol, São Paulo, BrazilUniversidade Federal de São Paulo, Fac Med, Dept Radiol, Lab Oncol Expt, São Paulo, BrazilInst Canc Estado São Paulo, Ctr Invest Translat Oncol, São Paulo, BrazilFed Univ Para, Hosp Univ Joao Barros Barreto, BR-66059 Belem, Para, BrazilFed Univ Para, Inst Ciencias Biol, Lab Citogenet Humana, BR-66059 Belem, Para, BrazilUniversidade Federal de São Paulo, Disciplina Genet, Dept Morfol & Genet, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ortopedia & Traumatol, São Paulo, BrazilUniversidade Federal de São Paulo, Fac Med, Dept Radiol, Lab Oncol Expt, São Paulo, BrazilWeb of Scienc

Doença de Alzheimer

This paper concisely reviews the genetics of Alzheimer Disease (AD). So far, three different genes have been implicated in AD. Specifically, the gene that codes for APP - the amyloid beta precursor protein, which is associated to dementia through intense brain deposition - the presenilin 1 gene (PS1) and the presenilin 2 gene (PS2). Both presenilin genes code for cellular membrane proteins and PS1 are responsible for approximately 40% of the early-onset familial cases. Genes that code for ApoE4, alpha-2 macroglobulin and cathepsin D, which are all involved in APP metabolism, have been considered as risk factors for AD. The ApoE4 gene is a risk factor in about 50% of the AD sporadic and late-onset cases. Several other genes that have been associated to AD are briefly discussed. Different strategies for genetic counseling of relatives are considered, and finally, ribosomal gene alterations are discussed as possible mechanisms underlying genetic progeroid syndromes such as AD.O artigo apresenta uma revisão sucinta dos aspectos genéticos da doença de Alzheimer e da metodologia empregada. Três genes distintos foram responsabilizados pela afecção até o momento: o da APP- responsável pela substância precursora da b-amilóide, a qual se deposita intensamente no cérebro dos afetados e está associada ao quadro demencial -, o gene da presenilina 1 (PS1) e o da presenilina 2 (PS2), proteínas de membrana celular. O gene da PS1 é responsável por cerca de 40% dos casos familiares e de acometimento precoce da DA . Os genes da ApoE4, da a-2-macroglobulina e da catepsina D, envolvidos no metabolismo da b-amilóide, foram caracterizados como fatores de risco para a DA. O gene da ApoE4 é fator de risco em cerca de 50% dos casos de DA esporádicos e de acometimento tardio. Muitos outros genes foram ainda associados à DA e são apresentados brevemente. São discutidas a conduta - quanto ao aconselhamento genético para familiares de afetados - e a utilização de diagnóstico molecular na predisposição genética à afecção. É apresentado como mecanismo comum às síndromes progeróides genéticas, como a DA, a alteração da atividade dos genes ribossômicos

Longitudinal lipid profile variations and clinical change in Alzheimer's disease dementia

Hypercholesterolemia and statin use have been unevenly associated with clinical change in Alzheimer's disease dementia. In this longitudinal study, 192 consecutive outpatients with late-onset Alzheimer's disease dementia were stratified according to APOE haplotypes, and followed for one year to investigate associations of lipid profile variations and lipophilic statin therapy with changes in cognition, caregiver burden, basic and instrumental functionality. Overall, 102 patients (53.1%) carried APOE4+ haplotypes and 90 (46.9%) carried APOE4- haplotypes189 patients (98.4%) used either a cholinesterase inhibitor, or Memantine, or both144 patients had dyslipidemias and 143 of them received statin therapy. Total cholesterol, LDL-cholesterol, Mini-Mental State Examination scores, and functional independence scores were significantly lower at the end of the follow-up, while Clinical Dementia Rating sum-of-boxes scores were higher. Exclusively for APOE4- carriers, rising LDL-cholesterol levels were associated with a trend toward improvements in the Index of Independence in Activities of Daily Living (beta=0.010rho= 0.16), whereas rising HDL-cholesterol levels were associated with lowered scores (beta = -0.051rho= 0.04). Lipophilic statin therapy had non-significant protective effects over Clinical Dementia Rating sum-of boxes score variations only for APOE4- carriers. APOE4- haplotypes might enhance lipid availability to protect neuronal membranes, thus overcoming their supposed dysfunction in cholesterol metabolism, while APOE4+ carriers have inefficient neural repair mechanisms. In conclusion, APOE haplotypes seem to influence the protective effects of lipid profile variations for patients with Alzheimer's disease dementia, but current evidence is insufficient to propose lipid-lowering drugs as specific anti-dementia therapy. (C) 2017 Elsevier B.V. All rights reserved.CAPES - Coordenacao de Aperfeicoamento de Pessoal de Nivel SuperiorFAPESP - The State of Sao Paulo Research FoundationFed Univ Sao Paulo UNIFESP, Escola Paulista Med, Dept Neurol & Neurosurg, Rua Botucatu 740, BR-04023900 Sao Paulo, SP, BrazilFed Univ Sao Paulo UNIFESP, Escola Paulista Med, Dept Morphol & Genet, Sao Paulo, SP, BrazilFed Univ Sao Paulo UNIFESP, Escola Paulista Med, Dept Neurol & Neurosurg, Rua Botucatu 740, BR-04023900 Sao Paulo, SP, BrazilCAPES: 1067/10FAPESP: 2015/10109-5Web of Scienc

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

MYC Insertions in Diffuse-type Gastric Adenocarcinoma

Background: MYC is important in gastric carcinogenesis. A few studies reported MYC translocation or insertion associated with gastric cancer. Materials and Methods: MYC copy number and its insertion, as well as the chromosomes in which MYC was inserted, were evaluated by fluorescence in situ hybridization assay in interphase and metaphase cells of 12 diffuse-type gastric cancer samples. MYC protein expression was evaluated by immunohistochemistry. Results: The presence of 3 MYC signals was the most frequent alteration. All cases also presented 4 and 5 MYC signals. In all samples, we observed chromosome 8 trisomy with MYC copies and MYC insertion into the chromosomes 2, 7, 14, 17, 18 and 22. All samples presented nucleic and cytoplasmic immunoreactivity. Conclusion: MYC cytoplasmic immunoreactivity can be the result of MYC insertion with the breakpoints within or close to the regions that are able to target the nucleus. MYC insertion and cytoplasmatic immunoreactivity may be a common characteristic of diffuse-type gastric cancer.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fed Univ Para, Inst Ciencias Biol, Lab Citogenet Humana, BR-66075900 Belem, Para, BrazilFed Univ Para, Joao de Barros Barreto Univ Hosp, BR-66075900 Belem, Para, BrazilUniv Fed Sao Paulo, Dept Morphol & Genet, Div Genet, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Morphol & Genet, Div Genet, Sao 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

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