Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Eur J Cancer ; 50(13): 2241-50, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24953332

RESUMO

BACKGROUND AND AIMS: Individuals with tumours showing mismatch repair (MMR) deficiency not linked to germline mutations or somatic methylation of MMR genes have been recently referred as having 'Lynch-like syndrome' (LLS). The genetic basis of these LLS cases is unknown. MUTYH-associated polyposis patients show some phenotypic similarities to Lynch syndrome patients. The aim of this study was to investigate the prevalence of germline MUTYH mutations in a large series of LLS patients. METHODS: Two hundred and twenty-five probands fulfilling LLS criteria were included in this study. Screening of MUTYH recurrent mutations, whole coding sequencing and a large rearrangement analysis were undertaken. Age, sex, clinical, pathological and molecular characteristics of tumours including KRAS mutations were assessed. RESULTS: We found a prevalence of 3.1% of MAP syndrome in the whole series of LLS (7/225) and 3.9% when only cases fulfilling clinical criteria were considered (7/178). Patients with MUTYH biallelic mutations had more adenomas than monoallelic (P=0.02) and wildtype patients (P<0.0001). Six out of nine analysed tumours from six biallelic MUTYH carriers harboured KRAS-p.G12C mutation. This mutation was found to be associated with biallelic MUTYH germline mutation when compared with reported series of unselected colorectal cancer cohorts (P<0.0001). CONCLUSIONS: A proportion of unexplained LLS cases is caused by biallelic MUTYH mutations. The obtained results further justify the inclusion of MUTYH in the diagnostic strategy for Lynch syndrome-suspected patients.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , DNA Glicosilases/genética , Mutação em Linhagem Germinativa , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Proteínas ras/genética
2.
Clin Immunol ; 119(2): 156-65, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16480927

RESUMO

Strong evidence suggests that microbial components are involved in the etiopathology of inflammatory bowel diseases (IBD). Since pathogen-associated molecular patterns are recognized by TLRs, dysregulation of TLR-mediated microbial recognition could be taking place in IBD patients. An in vitro assay with different TLR agonists was used to reproduce the immunostimulation via TLR ligands. Elevated TNFalpha production was found in response to LTA and Zymosan in 48% of active Crohn's disease and ulcerative colitis patients when compared to inactive patients or controls. The expression of CD14 did not differ in active patients, whereas TLR2 was significantly upregulated on monocytes from 71% of those patients with high production of TNFalpha. The marked increase of TNFalpha response to TLR2 ligands correlated with a higher TLR2 expression in a group of IBD patients, suggesting that an abnormal mechanism may provide an excess of inflammatory mediators during the active phase of IBDs.


Assuntos
Colite Ulcerativa/metabolismo , Doença de Crohn/metabolismo , Leucócitos Mononucleares/metabolismo , Receptor 2 Toll-Like/fisiologia , Fator de Necrose Tumoral alfa/biossíntese , Células Cultivadas , Colite Ulcerativa/sangue , Doença de Crohn/sangue , Feminino , Humanos , Interferon gama/sangue , Interleucina-6/sangue , Ligantes , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade
3.
Med. clín (Ed. impr.) ; 115(8): 299-301, sept. 2000.
Artigo em Espanhol | IBECS | ID: ibc-7144

RESUMO

Fundamento: La azatioprina es un fármaco inmunodepresor ampliamente utilizado en el tratamiento de diversos procesos autoinmunes. Los efectos adversos del tratamiento están en relación con la actividad de la tiopurina metiltransferasa (TPMT), enzima que interviene en el metabolismo de la azatioprina. La existencia de variantes alélicas del gen que codifica dicha enzima permite clasificar a los pacientes en tres grupos: de riesgo leve, moderado y alto de padecer una mielodepresión tras la administración de azatioprina. Pacientes y métodos: Se ha realizado el estudio de las variantes alélicas del gen de la TPMT en las posiciones 460 y 719 mediante reacción en cadena de la polimerasa y digestión con enzimas de restricción, en un enfermo con enfermedad de Crohn que presentó aplasia tras la administración de azatioprina, así como de sus familiares directos disponibles. Resultados: En la muestra del caso en estudio se identificó la variante alélica más frecuente del gen de la TPMT asociada a una actividad enzimática disminuida. La madre del paciente, así como su hermana, también presentaron esta variante. Conclusión: La identificación genotípica de las variantes alélicas del gen TPMT es un método eficaz para identificar a los pacientes con riesgo leve, moderado o grave de padecer una mielodepresión tras la administración de azatioprina (AU)


Assuntos
Pessoa de Meia-Idade , Adulto , Masculino , Feminino , Humanos , Próteses Valvulares Cardíacas , Polimorfismo Genético , Polimorfismo Genético , Fatores de Tempo , Infecções Relacionadas à Prótese , Mortalidade Hospitalar , Metiltransferases , Complicações Pós-Operatórias , Aplasia Pura de Série Vermelha , Azatioprina , Doença de Crohn , Imunossupressores , Emergências , Endocardite Bacteriana , Seguimentos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA