RESUMEN
IkappaBgamma is one member of a family of proteins that can inhibit the nuclear localization of nuclear factor-kappaB. However, the other specific functions of IkappaBgamma are still poorly understood, and its effects on tumor metastasis have not yet been characterized. We examined the consequences of targeting IkappaBgamma in melanoma cells using a hammerhead ribozyme. We developed stable transformant B16-F10 melanoma cell lines that express a ribozyme that targets mouse IkappaBgamma (IkappaBgamma-144-Rz). Tail-vein injection of B16-F10 cells that stably express IkappaBgamma-144-Rz into mice resulted in a significant reduction of the metastatic potential of these cells. IkappaBgamma-144-Rz-expressing B16 cells were shown to have increased transcriptional activity of nuclear factor-kappaB. We then showed that IkappaBgamma-144-Rz-expressing cells demonstrated both reduced invasion and increased apoptosis, suggesting the existence of pathways through which IkappaBgamma promotes melanoma metastasis. Using gene expression profiling, we identified a differentially expressed gene set that is regulated by the stable suppression of IkappaBgamma that may participate in mediating its anti-metastatic effects; we also confirmed the altered expression levels of several of these genes by quantitative real time polymerase chain reaction. Plasmid-mediated expression of IkappaBgamma-144-Rz produced a significant inhibition of the metastatic progression of B16-F10 cells to the lung and resulted in significant anti-invasive and pro-apoptotic effects on murine Lewis lung carcinoma cells. Our results suggest a novel role for IkappaBgamma in promoting the metastatic progression of melanoma.
Asunto(s)
Melanoma Experimental/genética , Melanoma Experimental/patología , Subunidad p50 de NF-kappa B/genética , FN-kappa B/genética , Invasividad Neoplásica/prevención & control , Metástasis de la Neoplasia/prevención & control , ARN Catalítico/genética , Animales , Clonación Molecular , Citometría de Flujo , Ratones , FN-kappa B/antagonistas & inhibidores , Invasividad Neoplásica/patología , Metástasis de la Neoplasia/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , ARN Neoplásico/genética , Transcripción Genética , Células Tumorales CultivadasRESUMEN
We report a case of necrobiotic xanthogranuloma that responded to treatment with chlorambucil. A 56-year-old man presented with a 5-year history of multiple, mildly pruritic, brown-to-violaceous plaques with central ulceration and atrophy involving the periorbital area, extremities, and trunk. Laboratory studies showed mild leukopenia and a monoclonal gammopathy of the IgG lambda type on serum protein immunoelectrophoresis. Histopathological evaluation revealed a dense histiocytic infiltrate with hyaline necrobiosis involving the dermis with extension to the subcutis. Multiple large multinucleated giant cells and scattered lymphocytes were seen. A diagnosis of necrobiotic xanthogranuloma was established. The patient was started on chlorambucil initially at 2 mg per day. The dose was later increased to 4 mg per day, which resulted in flattening and complete resolution of his skin lesions.
Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Clorambucilo/uso terapéutico , Granuloma/patología , Xantomatosis/patología , Relación Dosis-Respuesta a Droga , Granuloma/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Xantomatosis/tratamiento farmacológicoRESUMEN
BACKGROUND: Temporal hair loss has been reported to occur in up to 8.4% of patients after rhytidectomy. To date, no one has described the associated histopathologic findings. OBJECTIVE: The objective was to illustrate the microscopic findings seen in the affected area of hair loss after rhytidectomy. METHODS: Two punch biopsies from the temporal area were performed, and pathologic material was submitted. RESULTS: Histopathologic finding was suggestive of acute localized telogen effluvium. CONCLUSION: One mechanism for temporal hair loss after rhytidectomy is an acute localized telogen effluvium.