RESUMEN
Gastric cancer is one of the most common malignancies. DNA methylation is implicated in DNA mismatch repair genes deficiency. In the present study, we evaluated the methylation status of MLH1, MSH2, MSH6 and PMS2 in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosal of gastric cancer patients from Northern Brazil. We found that none of the nonneoplastic samples showed methylation of any gene promoter and 50% of gastric cancer samples showed at least one methylated gene promoter. Methylation frequencies of MLH1, MSH2, MSH6 and PMS2 promoter were 21.74%, 17.39%, 0% and 28.26% respectively in gastric cancer samples. MLH1 and PMS2 methylation were associated with neoplastic samples compared to nonneoplastic ones. PMS2 methylation was associated with diffuse- and intestinal-type cancer compared with normal controls. Intestinal-type cancer showed significant association with MLH1 methylation. Diffuse-type cancer was significantly associated with MSH2 methylation. Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that methylation is associated with gastric carcinogenesis. Methylation of mismatch repair genes was associated with gastric carcinogenesis and may be a helpful tool for diagnosis, prognosis and therapies. However, MSH6 does not seem to be regulated by methylation in our samples.
Asunto(s)
Humanos , Masculino , Adulto , Femenino , Persona de Mediana Edad , Metilación de ADN , Neoplasias Gástricas/genética , Reparación de la Incompatibilidad de ADN , Análisis de Secuencia de ADN , Brasil , Enzimas Reparadoras del ADN/genética , Regiones Promotoras GenéticasRESUMEN
Gastric cancer is the forth most frequent malignancy and the second most common cause of cancer death worldwide. DNA methylation is the most studied epigenetic alteration, occurring through a methyl radical addition to the cytosine base adjacent to guanine. Many tumor genes are inactivated by DNA methylation in gastric cancer. We evaluated the DNA methylation status of ANAPC1, CDKN2A and TP53 by methylation-specific PCR in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosa in individuals from Northern Brazil. All gastric cancer samples were advanced stage adenocarcinomas. Gastric samples were surgically obtained at the João de Barros Barreto University Hospital, State of Pará, and were stored at -80°C before DNA extraction. Patients had never been submitted to chemotherapy or radiotherapy, nor did they have any other diagnosed cancer. None of the gastric cancer samples presented methylated DNA sequences for ANAPC1 and TP53. CDKN2A methylation was not detected in any normal gastric mucosa; however, the CDKN2A promoter was methylated in 30.4 percent of gastric cancer samples, with 35 percent methylation in diffuse-type and 26.9 percent in intestinal-type cancers. CDKN2A methylation was associated with the carcinogenesis process for ~30 percent diffuse-type and intestinal-type compared to non-neoplastic samples. Thus, ANAPC1 and TP53 methylation was probably not implicated in gastric carcinogenesis in our samples. CDKN2A can be implicated in the carcinogenesis process of only a subset of gastric neoplasias.
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adenocarcinoma/genética , Metilación de ADN/genética , Neoplasias Gástricas/genética , Complejos de Ubiquitina-Proteína Ligasa/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Estudios de Casos y Controles , Reacción en Cadena de la Polimerasa , Regiones Promotoras Genéticas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologíaRESUMEN
The TP53 tumor suppressor gene codifies a protein responsible for preventing cells with genetic damage from growing and dividing by blocking cell growth or apoptosis pathways. A common single nucleotide polymorphism (SNP) in TP53 codon 72 (Arg72Pro) induces a 15-fold decrease of apoptosis-inducing ability and has been associated with susceptibility to human cancers. Recently, another TP53 SNP at codon 47 (Pro47Ser) was reported to have a low apoptosis-inducing ability; however, there are no association studies between this SNP and cancer. Aiming to study the role of TP53 Pro47Ser and Arg72Pro on glioma susceptibility and oncologic prognosis of patients, we investigated the genotype distribution of these SNPs in 94 gliomas (81 astrocytomas, 8 ependymomas and 5 oligodendrogliomas) and in 100 healthy subjects by the polymerase chain reaction-restriction fragment length polymorphism approach. Chi-square and Fisher exact test comparisons for genotype distributions and allele frequencies did not reveal any significant difference between patients and control groups. Overall and disease-free survivals were calculated by the Kaplan-Meier method, and the log-rank test was used for comparisons, but no significant statistical difference was observed between the two groups. Our data suggest that TP53 Pro47Ser and Arg72Pro SNPs are not involved either in susceptibility to developing gliomas or in patient survival, at least in the Brazilian population.
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , Glioma/genética , Polimorfismo de Nucleótido Simple , /genética , Apoptosis/genética , Brasil , Estudios de Casos y Controles , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Glioma/etiología , Glioma/mortalidad , Pronóstico , Análisis de SupervivenciaRESUMEN
The cancer is one of the most common and severe problems in clinical medicine, and nervous system tumors represent about 2% of the types of cancer. The central role of the nervous system in the maintenance of vital activities and the functional consequences of the loss of neurons can explain how severe brain cancers are. The cell cycle is a highly complex process, with a wide number of regulatory proteins involved, and such proteins can suffer alterations that transform normal cells into malignant ones. The INK4 family members (CDK inhibitors) are the cell cycle regulators that block the progression of the cycle through the R point, causing an arrest in G1 stage. The p14ARF (alternative reading frame) gene is a tumor suppressor that inhibits p53 degradation during the progression of the cell cycle. The PTEN gene is related to the induction of growth suppression through cell cycle arrest, to apoptosis and to the inhibition of cell adhesion and migration. The purpose of the present study was to assess the mutational state of the genes p14ARF, p15INK4b, p16INK4a, and PTEN in 64 human nervous system tumor samples. Homozygous deletions were found in exon 2 of the p15INK4b gene and exon 3 of the p16INK4a gene in two schwannomas. Three samples showed a guanine deletion (63 codon) which led to a loss of heterozygosity in the p15 gene, and no alterations could be seen in the PTEN gene. Although the group of patients was heterogeneous, our results are in accordance with other different studies that indicate that homozygous deletion and loss of heterozygosity in the INK4 family members are frequently observed in nervous system tumors.
Asunto(s)
Humanos , /genética , /genética , Neoplasias del Sistema Nervioso/genética , /genética , Análisis Mutacional de ADN/métodos , Eliminación de Gen , Homocigoto , Pérdida de Heterocigocidad , Neoplasias del Sistema Nervioso/patología , Reacción en Cadena de la Polimerasa , Fosfohidrolasa PTENRESUMEN
Gliomas are the most common tumors of the central nervous system. In spite of the marked advances in the characterization of the molecular pathogenesis of gliomas, these tumors remain incurable and, in most of the cases, resistant to treatments, due to their molecular heterogeneity. Gene PAX6, which encodes a transcription factor that plays an important role in the development of the central nervous system, was recently recognized as a tumor suppressor in gliomas. The objective of the present study was to analyze the mutational status of the coding and regulating regions of PAX6 in 94 gliomas: 81 astrocytomas (11 grade I, 23 grade II, 8 grade III, and 39 grade IV glioblastomas), 5 oligodendrogliomas (3 grade II, and 2 grade III), and 8 ependymomas (5 grade II, and 3 grade III). Two regulating regions (SX250 and EIE) and the 11 coding regions (exons 4-13, plus exon 5a resulting from alternative splicing) of gene PAX6 were analyzed and no mutation was found. Therefore, we conclude that the tumor suppressor role of PAX6, reported in previous studies on gliomas, is not due to mutation in its coding and regulating regions, suggesting the involvement of epigenetic mechanisms in the silencing of PAX6 in these tumors.
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , ADN de Neoplasias/genética , Glioma/genética , Mutación , Neoplasias del Sistema Nervioso Central/genética , Proteínas Represoras/genética , Proteínas de Homeodominio/genética , Proteínas del Ojo/genética , Astrocitoma , Secuencia de Bases , Análisis Mutacional de ADN , Epigénesis Genética , Ependimoma/genética , Factores de Transcripción Paired Box/genética , Silenciador del Gen , Oligodendroglioma/genética , Reacción en Cadena de la Polimerasa , Cartilla de ADN/genéticaAsunto(s)
Humanos , Donantes de Sangre , Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/fisiopatología , Inmunoensayo , Pruebas de Hemaglutinación , Pruebas Serológicas/métodos , Trypanosoma cruzi/patogenicidad , Exámenes Obligatorios/métodos , Valor Predictivo de las PruebasRESUMEN
En los enzimoinmunoensayos de segunda generación (EIA 2.0) se incrementó la sensibilidad y especificidad respecto de los de primera generación. Actualmente se emplean los equipos de tercera generación (EIA3.0) con el fin de acortar el período de ventana y mejorar el comportamiento de sus versiones anteriores. El objetivo de este trabajo es evaluar el comportamiento de EIA 3.0 y EIA 2.0 en la población de dadores de sangre (DS) de nuestro hospital y relacionarlos con un ensayo suplementario (LIA III), con especial énfasis en las distintas intensidades de reacción (RP) de ambos EIAs. Fueron estudiados 15.898 DS con reactivos Abbott HCV EIA 2.0 y 4.147 con Abbott HCV EIA 3.0 (Abbott Laboratoires, Wiesbaden, Alemania). Las muestras doblemente reactivas fueron evaluadas por InnoLIA III (Innogenetics, Bélgica). La prevalencia de DS seropositivos para HCV fue 1,17 por ciento por EIA 2.0 y 1,83 por ciento por EIA 3.0. Independientemente del valor de RP, el EIA 3.0 mostró una mayor frecuencia de muestras LIA III negativas e indeterminadas que el EIA 2.0 (negativas 44 por ciento versus 38 por ciento; indeterminadas 14 por ciento versus 4 por ciento). Este comportamiento fue similar en todos los valores de RP. Para DS EIA reactivos con RP>=4.0 el 100 por ciento fue LIA III positivo cuando se empleó EIA 2.0 y el 68 por ciento en los analizados con EIA 3.0. El perfil de bandas reactivas en LIA III fue similar para ambos equipos y se hace más completo e intenso al aumentar el RP. De estas observaciones se concluye que el EIA 3.0 posee una perfomance más pobre respecto de su versión anterior, con mayor porcentaje de resultados LIA III indeterminados y negativos, en casi todos los valores de RP. Esta elevada frecuencia de datos falso-positivos crea en el dador de sangre una preocupación innecesaria y hace necesario el empleo de pruebas suplementarias para su certificación, con el consiguiente incremento en el costo de la unidad de sangre estudiada y su posterior descarte.
Asunto(s)
Humanos , Reacciones Antígeno-Anticuerpo , Donantes de Sangre , Ensayo de Inmunoadsorción Enzimática , Anticuerpos contra la Hepatitis C/sangre , Técnicas para Inmunoenzimas/métodos , Manejo de EspecímenesAsunto(s)
Humanos , Masculino , Femenino , Embarazo , Adolescente , Adulto , Persona de Mediana Edad , Transfusión Sanguínea , Síndrome Hemolítico-Urémico , Intercambio Plasmático , Plasmaféresis , Púrpura Trombocitopénica Trombótica/complicaciones , Púrpura Trombocitopénica Trombótica/diagnóstico , Púrpura Trombocitopénica Trombótica/etiología , Púrpura Trombocitopénica Trombótica/fisiopatología , Púrpura Trombocitopénica Trombótica/historia , Púrpura Trombocitopénica Trombótica/mortalidad , Púrpura Trombocitopénica Trombótica/terapia , Aspirina/uso terapéutico , Fenitoína/uso terapéutico , Estudios de Seguimiento , Glucocorticoides/uso terapéutico , Prednisona/uso terapéutico , Recurrencia/prevención & control , Esplenectomía , Tasa de SupervivenciaRESUMEN
Se presenta un nuevo caso de asociacion de anemia hemolitica autoinmune (AHAI) con neoplasia de ovario, y se efectua revision de la literatura. Se trata de una paciente de 29 anos de edad que consulta en el noveno dia de su puerperio por anemia e ictericia. Al examen fisico se encontraron como datos de mayor interes, importante hepatomegalia y un tumor en hipogastrio que al examen ginecologico se interpreto como una formacion anexial derecha.Los estudios complementarios demostraron un cuadro de hiperhemolisis y una prueba de Coombs directa positiva de tipo IgM + complemento, evidenciando el autoanticuerpo especificidad anti-I.Ante la falta de respuesta al tratamiento de la anemia mediante corticosteroides, se decidio someter a la paciente a una laparotomia exploradora, tratando de relacionar la tumoracion abdominal con la hiperhemolisis. En el acto operatorio se descubrio un blastoma de ovario y nodulos de aspecto metastasico en higado. Se practico una anexohisterectomia total. La anatomia patologica informo carcinoma anaplasico de ovario derecho con diseminacion al ovario contralateral y al higado. Luego de la cirugia la anemia revirtio completamente, continuandose el tratamiento con poliquimioterapia hasta el momento actual