RESUMEN
Aberrant expression of vascular endothelial growth factor (VEGF) is associated with human prostate cancer (PCa) metastasis and poor clinical outcome. We found that both phosphorylation of cyclic AMP-responsive element-binding protein (CREB) and VEGF levels were significantly elevated in patient bone metastatic PCa specimens. A PCa ARCaP progression model demonstrating epithelial-to-mesenchymal transition exhibited increased CREB phosphorylation and VEGF expression as ARCaP cells became progressively more mesenchymal and bone-metastatic. Activation of CREB induced, whereas inhibition of CREB blocked, VEGF expression in ARCaP cells. CREB may regulate VEGF transcription via a hypoxia-inducible factor-dependent mechanism in normoxic conditions. Activation of CREB signaling is involved in the coordinated regulation of VEGF and may pre-dispose to PCa bone metastasis.
Asunto(s)
Neoplasias Óseas/secundario , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Próstata/patología , Factor A de Crecimiento Endotelial Vascular/genética , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/análisis , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Masculino , Regiones Promotoras Genéticas , Neoplasias de la Próstata/química , Neoplasias de la Próstata/metabolismo , Transcripción Genética , Factor A de Crecimiento Endotelial Vascular/sangreRESUMEN
Two genes, i.e. survival motor neuron (SMN) and neuronal apoptosis inhibitory protein (NAIP) have been mapped to the SMA region of chromosome 5q13. Both genes are frequently deleted or truncated in SMA patients. We have studied 26 patients with SMA types I-III, 29 first relatives, and 14 subjects with mild adult-onset type IV. DNA deletion genotypes were determined by PCR techniques amplifying exons 7 and 8 of SMN, and exon 5 of NAIP gene which distinguish SMN and NAIP telomeric copy from a non-pathogenic gene homologue as a centromeric copy. Results revealed the homozygous deletions of exon 7 and 8 of the SMN gene and exon 5 of the NAIP gene in 3/3 infants with SMA I and in 1/20 with SMA type II. Exons 7 and 8 of the SMN gene were homozygously deleted in 10/20 and only exon 7 in 6/20 children with SMA type II. The overall percentage of deletion cases observed was 77% in children with SMA types I-III. Adult patients with type IV SMA showed no homozygous deletion of exons 7, 8 and 5 of the SMN and NAIP genes. Also, all relatives had both a telomeric and centromeric SMN and NAIP copy. Deletion analysis of SMN and NAIP genes are a significant diagnostic tool, because there are clinical entities resembling SMA which most likely have another pathogenetic background.
Asunto(s)
Atrofia Muscular Espinal/genética , Proteínas del Tejido Nervioso/genética , Atrofias Musculares Espinales de la Infancia/genética , Adulto , Niño , Preescolar , Croacia , Análisis Mutacional de ADN , Exones , Eliminación de Gen , Humanos , LactanteRESUMEN
A case of neuro-cutaneous melanoma, in the course of which a bifocal melanoma of the cerebral hemisphere had developed, was used as a natural model for the study of the relation between tumorous and non-tumorous elements. The need is pointed out for the definition of such a cutaneous-meningeal syndrome before the development of a neoplasm. As tumours develop from the cells defining leptomeningeal melanosis, the possibility of a neuroradiological diagnosis of this process is accentuated, primarily by a minute examination of the sites characteristic of the disease. A premorbid detection of all such cases is imperative in order to introduce an early anti-tumour treatment.