The assessment of caveolin-1 (Cav-1) as a marker of tumor aggressiveness in pancreatic ductal adenocarcinoma (PDAC). In this study, we examined the expression of Cav-1 in 34 human PDAC tissue samples and the associated peritumoral tissues by immunohistochemistry and western blot. Additionally, we correlated Cav-1 expression with other tissue (Ki-67, p53) and serum (CA 19-9) tumor markers. In the tumor-derived tissue, both tumor cells and blood vessels expressed Cav-1. In contrast, in peritumoral tissue, Cav-1 expression was confined mainly to blood vessels and was only occasionally expressed in ductal or parenchymal cells. Western blot analysis confirmed the overexpression of Cav-1 in pancreatic tumors compared with peritumoral tissue. Cav-1 expression in tumor tissues was correlated with both the Ki-67 LI (r = 0.95, P < 0.0001) and p53 expression (chi2 = 9.91, P < 0.005). Overexpression of Cav-1 was associated with tumor size, grade and stage and Cav-1 expression in tumors was correlated with an increased serum level of CA 19-9 (r = 0.795, P < 0.001). Based on the results of this study, the inclusion of Cav-1 in a putative panel of biomarkers predicting pancreatic cancer aggressiveness is warranted.

We analysed the spatial and temporal distribution of apoptosis in human cerebellum development, during embryonic and fetal periods. Cerebella excised from two human embryos (8 weeks old) and eight fetuses (12-22 weeks old), were paraffin embedded and serially sectioned. Apoptotic cells were identified by propidium iodide staining, and TUNEL. In addition, immunohistochemistry for suicide receptor Fas(APO-1/CD95) was performed. We determined the distribution and percentage of apoptotic cells as well as Fas(APO-1/CD95)-positive cells in different regions and stages of development. Apoptotic cells were seen in both proliferative zones and postmitotic regions along the migratory pathways as well as in the developing cerebellar cortex in all examined stages. The Fas(APO-1/CD95) immunoreactivity was present in all examined stages in a small population of apoptotic cells: either neuroblasts or differentiated cells in postmitotic zones. These findings suggest that apoptosis drives the selection of the cells which are committed to differentiate during the early stages of cerebellar development. The differences between apoptotic cells distribution and Fas receptor expression suggest that cell selection is driven by different apoptotic pathways.

Ischemic preconditioning (IPC) of the brain describes the neuroprotection induced by a short, conditioning ischemic episode (CIE) to a subsequent severe (test) ischemic episode (TIE). Most of the supporting evidence for IPC is based on histological assessment, several days after TIE. The aim of this study is to investigate if changes induced by IPC can be detected within 30 min of reperfusion following the ischemic episode. A rat model of "four-vessel occlusion" transient global cerebral ischemia and parametric analysis of electrocorticogram were used. A control group was subjected directly to a 10 min TIE, and in a preconditioned group TIE was induced 48 h after a 3 min CIE. Quantitative histology was performed 48 h after TIE. Our key finding is that, 30 min after reperfusion, there is a significant increase in the electrocortical slow activity in the control group but not in the preconditioned group. Moreover the increase inversely correlates with the degree of electrocortical suppression during seconds 10 to 15 after the onset of the ischemic episode.The tolerance of the brain to an ischemic injury depends not only on the duration and severity of insufficient blood flow but also on various pre-and post-ischemic factors that are able to influence the post ischemic outcome. There is a lot of interest concerning the postischemic factors that can improve the recovery due to immediate clinical applicability. Nevertheless, recent experimental work focuses on the preischemic factors, that can increase the ischemic tolerance, among which the suppression of metabolic rate, the increase of brain tissue energy reserves and the inhibition of membrane permeability of cations are of particular importance [1].One of the most surprising discoveries in the search for preischemic neuroprotective factors was that exposure to short episodes of sublethal insults like ischemia, hypoxia, hyperthermic stresses and toxic agents results in a subsequent resistance to severe ischemic injury. The phenomenon of

We investigated the apoptosis at the beginning of human cerebral cortex development, in the 6th week of embryogenesis, Carnegie stages 16 and 17. Attention was focused on the dorsal wall of the telencephalon to the ventricular zone of proliferation and to the postmitotic zone with beginning of neuronal migration. We identified apoptotic cells in tissue sections by propidium iodide staining, TUNEL and immunohistochemistry for Fas(APO-1/CD95). We determined the distribution and the percentage (reported to the propidium iodide stained nuclei) of apoptotic TUNEL-positive and Fas(APO-1/CD95)-positive cells. TUNEL-positive apoptotic cells in the proliferative zone were 20% in stage 16 and 60% in stage 17. TUNEL-positive apoptotic cells in the postmitotic zone were 8% in stage16 and 30% in stage 17. CD95-positive apoptotic cells in the proliferative zone were 5% in stage 16 and 2% in stage 17. There were no CD95-positive cells in the postmitotic zone. We evidentiated the presence of the suicide receptor Fas(APO-1/CD95) only on a small population of apoptotic neuroblasts in the proliferative zone. The differences between apoptotic distribution and receptors in early corticogenesis suggest that different apoptotic pathways drive the selection of neuronal populations.

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