Biomedical subjects

Paola Cavalla

Publications and source records attributed to Paola Cavalla.

3 recordsLinked to original sources

PubMed2005

Grey matter pathology in multiple sclerosis.

The aim of our study is to evaluate the extent and distribution of grey matter demyelinating lesions in multiple sclerosis (MS), addressing also neuronal loss and synaptic loss. Whole coronal sections of 6 MS brains and 6 control brains were selected. Immunohistochemistry was performed for myelin basic protein, neurofilaments, synaptophysin, ubiquitin, and activated caspase-3. Neuronal density and optical density of synaptophysin staining were estimated in cortical lesions and compared with those observed in corresponding areas of normal (i.e. nondemyelinated) cortex in the same section. Demyelinating lesions were observed in the cerebral cortex, in the thalamus, basal ganglia, and in the hippocampus. The percentage of demyelinated cortex was remarkable in 2 cases of secondary progressive MS (48% and 25.5%, respectively). Neuronal density was significantly reduced in cortical lesions (18-23% reduction), if compared with adjacent normal cortex, in the 2 cases showing the higher extent of cortical demyelination; in the same cases, very rare apoptotic neurons expressing caspase-3 were observed in cortical lesions and not in adjacent normal cortex. No significant decrease in optical density of synaptophysin staining was observed in cortical lesions. Grey matter demyelination and neuronal loss could contribute to disability and cognitive dysfunctions in MS.

Adult↗

PubMed2003

Deregulation of the p14ARF/Mdm2/p53 pathway and G1/S transition in two glioblastoma sets.

Sixty-one glioblastomas have been studied, subdivided into the categories of classic glioblastomas (GBM) and glioblastomas with astrocytic (GBA) and oligodendroglial (GBO) differentiated areas. On surgical samples, TP53, Mdm2, CDKN2A/p16-p14 alterations were studied by molecular biology techniques and by immunohistochemistry. It has been found that Mdm2 amplification was more frequent in GBM than in GBA and GBO, that p14ARF was inactivated in a high percentage of cases in the three tumor categories. Both these and other alterations did not reach a statistical significance, with the exception of CDKN2A/p16 homozygous deletion which showed the highest frequency in GBO. The latter finding could be in line with the observation that CDKN2A/p16 inactivation is a step in the molecular pathway to tumor progression in oligodendrogliomas. TP53 mutations and Mdm2 amplifications were mutually exclusive, whereas TP53 mutations and CDKN2A/p14 inactivation coexisted in 5 cases. The alterations of the p53/Mdm2/p14ARF pathway occurred in 73% of cases and in 80% of cases if CDKN2A homozygous deletions were associated. All glioblastomas with gemistocytic areas showed p14ARF inactivation. Immunohistochemistry showed higher percentages of positivity in comparison with molecular genetics, but with similar variations.

Brain Neoplasms↗

PubMed2002

Inverse relationship between p27/Kip.1 and the F-box protein Skp2 in human astrocytic gliomas by immunohistochemistry and Western blot.

The F-box protein Skp2 regulates G1-S transition by controlling p27/Kip.1. The deregulated expression of p27/Kip.1 plays a critical role in the pathogenesis of many human tumors. Its cellular levels depend on ubiquitin-mediated degradation. Recently, Skp2 has been demonstrated to mediate p27/Kip.1 degradation and to have oncogenic properties. In a series of astrocytic gliomas, immunohistochemistry and Western blot of p27/Kip.1 and Skp2 have been compared. p27/Kip.1 decreased with anaplasia and almost disappeared in glioblastomas (GBM), whereas Skp2 was absent or poorly expressed in well differentiated astrocytomas and it was diffusely or focally expressed in most GBM. Since the expression of Skp2 increases during G1-S transition, the correlation of Skp2 levels with malignancy might simply reflect the highest percentage of proliferating cells in anaplastic gliomas or alternatively be instrumental to p27/Kip.1 degradation.

Astrocytes↗