EPB41L3, TSP-1 and RASSF2 as new clinically relevant prognostic biomarkers in diffuse gliomas.

Hypermethylation of tumor suppressor genes is one of the hallmarks in the progression of brain tumors. Our objectives were to analyze the presence of the hypermethylation of EPB41L3, RASSF2 and TSP-1 genes in 132 diffuse gliomas (astrocytic and oligodendroglial tumors) and in 10 cases of normal brain, and to establish their association with the patients' clinicopathological characteristics. Gene hypermethylation was analyzed by methylation-specific-PCR and confirmed by pyrosequencing (for EPB41L3 and TSP-1) and bisulfite-sequencing (for RASSF2). EPB41L3, RASSF2 and TSP-1 genes were hypermethylated only in tumors (29%, 10.6%, and 50%, respectively), confirming their cancer-specific role. Treatment of cells with the DNA-demethylating-agent 5-aza-2'-deoxycytidine restores their transcription, as confirmed by quantitative-reverse-transcription-PCR and immunofluorescence. Immunohistochemistry for EPB41L3, RASSF2 and TSP-1 was performed to analyze protein expression; p53, ki-67, and CD31 expression and 1p/19q co-deletion were considered to better characterize the tumors. EPB41L3 and TSP-1 hypermethylation was associated with worse (p = 0.047) and better (p = 0.037) prognosis, respectively. This observation was confirmed after adjusting the results for age and tumor grade, the role of TSP-1 being most pronounced in oligodendrogliomas (p = 0.001). We conclude that EPB41L3, RASSF2 and TSP-1 genes are involved in the pathogenesis of diffuse gliomas, and that EPB41L3 and TSP-1 hypermethylation are of prognostic significance.

Hemorragia intraparenquimatosa por una malformación arteriovenosa en una paciente con esclerosis tuberosa / Intracranial hemorrhage from an arteriovenous malformation (AVM) in a tuberous sclerosis patient

Describimos el caso de una paciente diagnosticada previamente de esclerosis tuberosa que ingresó de urgencia por una hemorragia intraparenquimatosa debido a una malformación arteriovenosa. La paciente fue intervenida mejorando su sintomatología clínica. A pesar de que la asociación de esclerosis tuberosa y hemorragia intracerebral es conocida en la bibliografía nunca antes se había descrito asociada a una malformación arteriovenosa (AU)

Carbonyl reductase and NADPH cytochrome P450 reductase activities in human tumoral versus normal tissues.

The use of bioreductive agents in enzyme-directed bioreductive therapy has been proposed to take advantage not only of hypoxia in tumours, but also of the presence of reductases that metabolise such compounds. In this study, we studied the activities of NADPH cytochrome P450 reductase (P450R) and carbonyl reductase (CR) in 17 human lung tumours and 18 human breast tumours, together with the corresponding normal tissues. For lung cancer but not for breast cancer there was a significant difference in the CR activity between normal and tumour tissue. CR activity was increased with respect to the normal tissue between 2-fold and 40-fold indicating heterogeneity in tumour samples. No relationship was found between CR activity and the histological type, tumoral grade or TNM stage of the tumours. Although some variation in P450R activity in tumoral versus normal tissues was found in the majority of the samples studied, no significant differences could be demonstrated.

Paraspinal muscle pathology in experimental scoliosis.

Paraspinal muscle biopsies from ten rabbits with experimentally induced scoliosis and from four healthy controls were analyzed histologically and histochemically. Scoliosis was induced by two different methods: six animals underwent unilateral damage of the dorsal column of the spinal cord (mean curve: 22 degrees) and four costotransversectomy (mean curve: 47 degrees). In eight scoliotic animals myopathic changes were detected on the muscles of the concave side. Only those animals which underwent costotransversectomy showed a neuropathic pattern with cronic denervation changes on the convex side. As regards the fiber type distribution, the control group showed a higher percentage of type-I fibers, which were similar on both sides of the spinal cord. No fiber proportion asymmetry could be detected in the muscles on the concave side in normal or scoliotic rabbits. There was a tendency to depart from normal values, in two different ways, on the convex side of scoliotic animals. Thus, in contrast to the medullary damage group, the muscles of the costotransversectomized rabbits showed an increased proportion of type-I fibers. Taken together, our findings support the hypothesis that myopathic changes as observed in human idiopathic scoliosis are a consequence of the postural deformity. Fiber type distribution does not appear to be related to the curvature in the same way.

Scoliosis induced by medullary damage: an experimental study in rabbits.

To date, there have been no reports of experiments designed to induce scoliosis by direct damage of different areas of the spinal cord. In a series of rabbits with medullary damage, the authors attempted selectively to interrupt the pathways that mediate proprioceptive input. Unilateral lesion of the dorsal column and posterior horn of the spinal cord was performed using three different techniques: coagulation with laser, stereotaxic microcoagulation, and longitudinal electrocoagulation. Of 32 operated rabbits, 17 developed scoliosis, exhibiting clear pathologic damage of the spinal cord. Electrophysiologic study, including EMG and analysis of the tonic -- vibratory reflex, was performed on 10 rabbits with medullary damage (scoliotic and non-scoliotic) and 12 matched controls. The data suggest disturbance of the sensory afferences that control the postural tone and consequent muscular imbalance, expressed as reduced activity in the muscles of the convex side. This work supports the view that loss of proprioceptive neural impulses caused by medullary damage can induce scoliosis.