RESUMO
INTRODUCTION: Helicobacter pylori infection is an established risk factor for gastric cancer development, but the exact underlying mechanism still remains obscure. The inactivation of tumor suppressor genes such as p53 and p27(KIP1) is a hypothesized mechanism, although there is no consensus regarding the influence of H. pylori cagA(+) in the development of these genetic alterations. GOALS: To verify the relationship among H. pylori infection, p53 mutations and p27(Kip1) Protein (p27) expression in gastric adenocarcinomas (GA) seventy-four tissues were assayed by PCR for H. pylori and cagA presence. Mutational analysis of p53 gene was performed by single-strand conformation polymorphism (SSCP). Seventy tissues were analyzed by an immunohistochemical method for p27 expression. RESULTS: From the samples examined, 95% (70/74) were H. pylori positive, 63% cagA(+). Altered p53 electrophoretic mobility was found in 72% of cases and significantly more frequent in the presence of cagA. Considerable reduction in p27 expression (19%) was found with a tendency for association between cagA(+) and p27(-), although the results were not statistically significant. Concomitant alterations of both suppressor genes were detected in 60% of cases. In the cases cagA(+), 66.7% of them had these concomitant alterations. CONCLUSIONS: The data suggest that H. pylori cagA(+) contributes to p53 alteration and indicate that concomitant gene inactivation, with reduced p27 expression, may be a mechanism in which H. pylori can promote the development and progression of gastric cancer.
Assuntos
Adenocarcinoma/microbiologia , Genes p53 , Infecções por Helicobacter/genética , Helicobacter pylori/isolamento & purificação , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Mutação , Neoplasias Gástricas/microbiologia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Inibidor de Quinase Dependente de Ciclina p27 , Feminino , Inativação Gênica , Infecções por Helicobacter/metabolismo , Helicobacter pylori/genética , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Adulto JovemRESUMO
OBJECTIVE: Decreases in p27(KIP1) and C-MYC expression have been associated with Helicobacter pylori infection. Furthermore, C-MYC seems to be a transcriptional repressor of p27(KIP1). Therefore, in a series of gastric adenocarcinomas we studied the association of p27(KIP1) expression with H. pylori genotype (vacA, cagA, cagE and virB11) and the involvement of C-MYC in this process. MATERIAL AND METHODS: Expression of p27(KIP1) and C-MYC was determined by immunohistochemistry in 84 gastric adenocarcinoma samples and H. pylori infection and genotype were determined by polymerase chain reaction. RESULTS: Most p27(KIP1)-negative cases (94.0%) were H. pylori-positive and 44.8% were C-MYC-positive. In the diffuse gastric cancer subtype, p27-negative-C-MYC-positive was the most frequent combination (cluster II), and was associated with the more pathogenic H. pylori strains. Although an association with p27(KIP1) and H. pylori strain was found in the intestinal gastric cancer subtype, negativity for p27(KIP1) and C-MYC markers was the most frequent cluster, followed by cluster II, and both were present, independent of the H. pylori genotype. CONCLUSIONS: Reduced expression of p27(KIP1) was closely linked to H. pylori infection, and was dependent on the more pathogenic strains. Moreover, intestinal and diffuse subtypes showed distinct carcinogenic pathways influenced by H. pylori strains. These data add insight to the differential influence and relevance of H. pylori genotype in gastric cancer development.
Assuntos
Adenocarcinoma/genética , Infecções por Helicobacter/genética , Helicobacter pylori/genética , Helicobacter pylori/patogenicidade , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Distribuição de Qui-Quadrado , Inibidor de Quinase Dependente de Ciclina p27 , Eletroforese em Gel de Ágar , Feminino , Gastrectomia , Genótipo , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Neoplasias Gástricas/cirurgiaRESUMO
AIM: To investigate the interrelationship between H pylori and Epstein-Barr virus (EBV) infection in the gastric carcinogenesis having in focus the p53 mutation and the c-Myc, Bcl-2 and Bax expression. METHODS: seventy-one gastric carcinoma tissues were assessed by polymerase chain reaction (PCR) for H pylori and in situ hybridization for EBV. c-Myc, Bcl-2 and Bax expression were detected by immunohistochemistry and single-stranded conformational polymorphism (SSCP) for p53 mutation. RESULTS: The positivity rates for H pylori and EBV were 94.4% and 8.45%, respectively. The majority of the cases displayed only the H pylori presence. All EBV positive cases were also H pylori positive. None infectious agent was observed in 5.55% of the cases. The intestinal type tumor was more frequent in the co-infected and non-infected groups. The female predominated in the non-infected group showing statistical significance (70.4% vs 29.6%, P = 0.039). The Bcl-2 was only detected in the group exclusively infected by H pylori. However, c-Myc and Bax were detected in the three groups but with a low frequency in the co-infected group. Mutation of p53 was present in all groups, with the highest frequencies in the H pylori positive groups. CONCLUSION: The frequency of H pylori infection in gastric carcinomas was high. The presented data indicated that gastric carcinogenesis has different pathways depending of the presence of the two investigated infectious agents, suggesting a possible involvement of H pylori with apoptotic process. The low expression of c-Myc and Bax in the EBV-positive groups suggests that EBV may inhibit the expression of these proteins. Nevertheless, p53 mutation shows to be a relevant alteration, independent of both infectious agents.
Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Genes p53 , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Neoplasias Gástricas , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo , Adolescente , Adulto , Idoso , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr , Feminino , Infecções por Helicobacter/metabolismo , Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myc/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Proteína Supressora de Tumor p53/genética , Proteína X Associada a bcl-2/genéticaRESUMO
Os fungos säo tidos como um dos microrganismos mais dispersos pelo ar. A contaminaçäo ambiental fúngica, além de ser frequente, proporciona a açäo destes seres vivos como agentes patogênicos de doenças respiratórias e oportunistas. Este estudo objetivou avaliar a contaminaçäo fúngica do ar da Clínica de Periodontia da Faculdade de Odontologia da Universidade Federal de Goiás (FO/UFG). As amostras foram coletadas em placas de Petri aberta, contendo ágar infusão cérebro-coraçäo, mediante a sua exposiçäo ao ambiente por 30 minutos, após atendimento dos pacientes. As colônias fúngicas desenvolvidas foram repicadas em ágar Sabouraud e identificadas por características macroscópicas e microcultivo. Os fungos detectados compreenderam 6 cepas de Aspergillus sp.;1 de Penicillium sp.; 1 de Curvularia sp.; 1 de Mycella sterelia; 1 Botrytis sp. e 2 fungos filamentosos negros; além de um isolado bacteriano Nocardia sp. O resultado mostrou que as condiçöes ambientais da clínica de Periodontia não estavam adequadas e medidas de controle devem ser revistas
