RESUMO
PURPOSE: Peripheral T-cell lymphomas (PTCL) are a heterogeneous entity of neoplasms with poor prognosis, a lack of effective therapies, and a largely unknown molecular pathology. Deregulated NF-κB activity has been associated with several lymphoproliferative diseases, but its importance in T-cell lymphomagenesis is poorly understood. We investigated the function of the NF-κB-inducing kinase (NIK), in this pathway and its role as a potential molecular target in T-cell lymphomas. EXPERIMENTAL DESIGN: We used immunohistochemistry to analyze the expression of different NF-κB members in primary human PTCL samples and to study its clinical impact. With the aim of inhibiting the pathway, we used genetic silencing of NIK in several T-cell lymphoma cell lines and observed its effect on downstream targets and cell viability. RESULTS: We showed that the NF-κB pathway was activated in a subset of PTCLs associated with poor overall survival. NIK was overexpressed in a number of PTCL cell lines and primary samples, and a pivotal role for NIK in the survival of these tumor cells was unveiled. NIK depletion led to a dramatic induction of apoptosis in NIK-overexpressing cell lines and also showed a more pronounced effect on cell survival than inhibitor of kappa B kinase (IKK) knockdown. NIK silencing induced a blockage of both classical and alternative NF-κB activation and reduced expression of several prosurvival and antiapoptotic factors. CONCLUSIONS: The results of the present study indicate that NIK could be a promising therapeutic target in these aggressive malignancies.
Assuntos
Linfoma de Células T/enzimologia , NF-kappa B/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Linfoma de Células T/mortalidade , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Modelos de Riscos Proporcionais , Proteínas Serina-Treonina Quinases/genética , RNA Interferente Pequeno/genética , Linfócitos T/enzimologia , Transcriptoma , Quinase Induzida por NF-kappaBRESUMO
OBJECTIVES: To report one case of retroperitoneal cystic lymphangioma in an adult patient. METHODS: We describe the case of a 70 year-old female patient who complained of periumbilical pain and progressive increases of abdominal perimeter over a few months. Physical examination showed a great abdominal mass; CT scan confirmed its cystic nature. The indication of surgery was established. RESULTS: complete lesion excision. Pathology report showed the definitive diagnosis of cystic lymphangioma. No evidence of disease after one year. CONCLUSIONS: We emphasize that it is an unfrequent type of retroperitoneal neoplasias in the adult age. We concur with other authors in the importance of complete excision.
Assuntos
Linfangioma Cístico , Neoplasias Retroperitoneais , Idoso , Feminino , Humanos , Linfangioma Cístico/diagnóstico , Neoplasias Retroperitoneais/diagnósticoRESUMO
OBJETIVO: Presentación de un caso de linfangiomaquístico retroperitoneal en adulto.METODO: Describimos el caso de una paciente mujer de70 años que refiere en los últimos meses dolor periumbilicaly sensación de aumento progresivo del perímetroabdominal. La exploración física evidenció una gran masaabdominal, confirmándose su carácter quístico en la tomografíaaxial computerizada. Se indicó cirugía.RESULTADOS: Extirpación completa de la lesión. El estudioanatomopatológico permitió un diagnóstico definitivocompatible con linfangioma quístico. No evidencia derecidiva tras un año de la intervención.CONCLUSIONES: Destacamos la infrecuencia de estetipo de neoplasias retroperitoneales en la edad adulta.Coincidimos con otros autores en la importancia de la exéresiscompleta en este tipo de entidades
OBJECTIVES: To report one case of ;;retroperitoneal cystic lymphangioma in an adult patient. ;;METHODS: We describe the case of a 70-year-old female ;;patient who complained of periumbilical pain and ;;progressive increases of abdominal perimeter over a few ;;months. Physical examination showed a great abdominal ;;mass; CT scan confirmed its cystic nature. The indication ;;of surgery was established. ;;RESULTS: complete lesion excision. Pathology report ;;showed the definitive diagnosis of cystic lymphangioma. ;;No evidence of disease after one year. ;;CONCLUSIONS: We emphasize that it is an unfrequent ;;type of retroperitoneal neoplasias in the adult age. We ;;concur with other authors in the importance of complete ;;excision
