RESUMEN
Campylobacter jejuni is a major pathogen in bacterial gastroenteritis worldwide and can cause bacteremia in severe cases. C. jejuni is highly structured into clonal lineages of which the ST677CC lineage has been overrepresented among C. jejuni isolates derived from blood. In this study, we characterized the genomes of 31 C. jejuni blood isolates and 24 faecal isolates belonging to ST677CC in order to study the genome biology related to C. jejuni invasiveness. We combined the genome analyses with phenotypical evidence on serum resistance which was associated with phase variation of wcbK; a GDP-mannose 4,6-dehydratase involved in capsular biosynthesis. We also describe the finding of a Type III restriction-modification system unique to the ST-794 sublineage. However, features previously considered to be related to pathogenesis of C. jejuni were either absent or disrupted among our strains. Our results refine the role of capsule features associated with invasive disease and accentuate the possibility of methylation and restriction enzymes in the potential of C. jejuni to establish invasive infections. Our findings underline the importance of studying clinically relevant well-characterized bacterial strains in order to understand pathogenesis mechanisms important in human infections.
Asunto(s)
Campylobacter jejuni/genética , Genoma Bacteriano , Proteínas Bacterianas/química , Proteínas Bacterianas/clasificación , Proteínas Bacterianas/genética , Campylobacter jejuni/aislamiento & purificación , Campylobacter jejuni/patogenicidad , Hibridación Genómica Comparativa , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Bacteriano/metabolismo , Heces/microbiología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Filogenia , Análisis de Secuencia de ADN , Serogrupo , Suero/microbiología , VirulenciaRESUMEN
Helicobacter pylori infection is the most common cause of gastritis, gastric ulcer and adenocarcinoma. It has proven difficult to cure because of its capability to develop strains resistant to antibiotics. The effect of three strains of lactic acid bacteria (LAB) and bovine colostral preparations on the adhesion of H. pylori NCTC 11637 on gastric adenocarcinoma (AGS) cells and on the interleukin (IL)-8 production was studied. Before infection, H. pylori were pretreated with Lactobacillus plantarum MLBPL1, Lactobacillus rhamnosus GG, Lactococcus lactis, or with a colostral preparation with or without specific H. pylori antibodies. The relative number of H. pylori adhered on AGS cells was determined by urease test. IL-8 produced by the cells was studied by enzyme-linked immunosorbent assay. Colostral preparations with and without specific antibodies reduced the adhesion of H. pylori on AGS cells in a dose-dependent manner. Live LAB at a concentration of 10(10) CFU/ml reduced the adhesion by approximately 50% (P < 0.05). After the infection of AGS cells by H. pylori, the IL-8 level rose up to about 10-fold (5500 +/- 1600 pg/ml). Pretreatment of H. pylori with colostral preparations or high concentrations of LAB prevented this IL-8 rise. Similar effect was seen with live and heat-killed LAB, the live LAB being more effective. Heat-killed LAB at a concentration of 10(10) CFU/ml rose the IL-8 level of non-infected cells significantly. Suppression of IL-8 production by LAB or colostral products could have a suppressive effect on inflammation in Helicobacter infection.
Asunto(s)
Anticuerpos/farmacología , Productos Biológicos/farmacología , Calostro/metabolismo , Infecciones por Helicobacter/microbiología , Helicobacter pylori , Lactobacillus/metabolismo , Probióticos/farmacología , Adenocarcinoma/inmunología , Adenocarcinoma/metabolismo , Adenocarcinoma/microbiología , Animales , Anticuerpos/inmunología , Adhesión Bacteriana/efectos de los fármacos , Adhesión Bacteriana/inmunología , Productos Biológicos/metabolismo , Bovinos , Línea Celular Tumoral , Calostro/inmunología , Medios de Cultivo Condicionados/metabolismo , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta Inmunológica , Femenino , Helicobacter pylori/fisiología , Interleucina-8/biosíntesis , Embarazo , Probióticos/metabolismoRESUMEN
Some oral squamous cell carcinomas (OSCCs) overexpress epidermal growth factor receptor (EGFR) but little is known about the receptor system overall during oral carcinogenesis. We studied all four ERBB receptors (EGFR, ERBB2-4) in developing (n=2), normal (n=7), dysplastic (n=23) and malignant (n=26) oral epithelia by means of immunohistochemistry. The investigations were supplemented by conducting reverse transcription-polymerase chain reactions in relation to 13 OSCC samples. All four ERBB receptors were detected in developing oral epithelium and, to a lesser degree, in mature oral epithelium. An increase in EGFR immunoreactivity was seen in 61% and 54% of dysplasias and OSCCs, respectively. The corresponding percentages for ERBB2 were 48 and 12, for ERBB3 48 and 43. ERBB4 nuclear staining was increased in 30% of dysplasias and 26% of OSCCs. Changes in ERBB receptor mRNA levels were not statistically significant. The results show that ERBB receptor profiles are specific to each tumour. Increased nuclear translocation of ERBB4 in some OSCCs may alter transcription of target genes and be associated with cancer progression. This information may be useful for clinicians as EGFR inhibitors are becoming treatment options in modern oncology.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Mucosa Bucal/metabolismo , Neoplasias de la Boca/metabolismo , Proteínas Tirosina Quinasas Receptoras/análisis , Adulto , Anciano , Carcinoma de Células Escamosas/genética , Receptores ErbB/análisis , Genes erbB , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Mucosa Bucal/embriología , Mucosa Bucal/patología , Neoplasias de la Boca/genética , Ploidias , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/patología , ARN Mensajero/análisis , Proteínas Tirosina Quinasas Receptoras/genética , Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptor ErbB-2/análisis , Receptor ErbB-3/análisis , Receptor ErbB-4 , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Coloración y Etiquetado , Estadísticas no ParamétricasRESUMEN
Cancer results from multiple genomic changes that affect DNA and its gene expression. The DNA sequences may be gained, lost or amplified, or translocated into different parts of the genome to form a fusion gene with oncogenic properties. The occurrence of specific chromosomal aberrations may be restricted to only one cancer type and it may be considered a primary carcinogenic event. Furthermore, the aberration profiles may be used to cluster tumors with similar origins. A variety of techniques exist for the detection of specific chromosomal and gene expression changes. However, the etiology of these molecular alterations remains unclear. Here we discuss the roles of Helicobacter pylori and asbestos burden as carcinogens that cause gastric cancer, mesothelioma and lung cancer.
Asunto(s)
Amianto/toxicidad , Carcinógenos/toxicidad , Helicobacter pylori/patogenicidad , Neoplasias/genética , Cromatina/genética , ADN/genética , Humanos , Neoplasias/diagnóstico , Neoplasias/microbiologíaRESUMEN
DNA copy number amplifications activate oncogenes and are hallmarks of nearly all advanced tumors. Amplified genes represent attractive targets for therapy, diagnostics and prognostics. To investigate DNA amplifications in different neoplasms, we performed a bibliomics survey using 838 published chromosomal comparative genomic hybridization studies and collected amplification data at chromosome band resolution from more than 4500 cases. Amplification profiles were determined for 73 distinct neoplasms. Neoplasms were clustered according to the amplification profiles, and frequently amplified chromosomal loci (amplification hot spots) were identified using computational modeling. To investigate the site specificity and mechanisms of gene amplifications, colocalization of amplification hot spots, cancer genes, fragile sites, virus integration sites and gene size cohorts were tested in a statistical framework. Amplification-based clustering demonstrated that cancers with similar etiology, cell-of-origin or topographical location have a tendency to obtain convergent amplification profiles. The identified amplification hot spots were colocalized with the known fragile sites, cancer genes and virus integration sites, but global statistical significance could not be ascertained. Large genes were significantly overrepresented on the fragile sites and the reported amplification hot spots. These findings indicate that amplifications are selected in the cancer tissue environment according to the qualitative traits and localization of cancer genes.