Prognostic impact of chromosomal aberrations and GNAQ, GNA11 and BAP1 mutations in uveal melanoma.

Purpose: To evaluate clinico-pathological and molecular prognostic factors in a well-defined series of posterior uveal melanoma (UM) with focus on chromosomal aberrations and mutations in the GNAQ, GNA11 and BRCA1-associated protein 1 (BAP1) genes.

Methods: Formalin-fixed paraffin-embedded (FFPE) tissue samples were obtained from 50 consecutive eyes enucleated for UM between 1993 and 2005. The material was tested for loss of chromosome 3 and gain of chromosome 8q gene signatures by selective molecular gene markers using multiplex ligation-dependent probe amplification (MLPA), and for DNA mutations in the GNAQ, GNA11 and BAP1 genes.

Age-Dependent Association between Protein Expression of the Embryonic Stem Cell Marker Cripto-1 and Survival of Glioblastoma Patients.

Exploring the re-emergence of embryonic signaling pathways may reveal important information for cancer biology. Nodal is a transforming growth factor-β (TGF-β)-related morphogen that plays a critical role during embryonic development. Nodal signaling is regulated by the Cripto-1 co-receptor and another TGF-β member, Lefty.

EGFR wild-type amplification and activation promote invasion and development of glioblastoma independent of angiogenesis.

Angiogenesis is regarded as a hallmark of cancer progression and it has been postulated that solid tumor growth depends on angiogenesis. At present, however, it is clear that tumor cell invasion can occur without angiogenesis, a phenomenon that is particularly evident by the infiltrative growth of malignant brain tumors, such as glioblastomas (GBMs). In these tumors, amplification or overexpression of wild-type (wt) or truncated and constitutively activated epidermal growth factor receptor (EGFR) are regarded as important events in GBM development, where the complex downstream signaling events have been implicated in tumor cell invasion, angiogenesis and proliferation.

The cuprizone model: regional heterogeneity of pathology.

The cuprizone model is a model of de- and remyelination secondary to oligodendrocyte death, likely to be mediated by an inhibition of mitochondrial function. The aim of this study was to characterize histopathological changes associated with de/remyelination in grey and white matter at different disease stages in C57Bl/6 mice after per oral administration of cuprizone. Oligodendrocyte loss, astrocytosis and complement activation was detected in areas of demyelination.

Transscleral optical spectroscopy of uveal melanoma in enucleated human eyes.

Purpose: The aims of this study were to use transscleral optical spectroscopy to analyze normal and tumor-infiltrated areas of enucleated human eyes, and to characterize the spectral properties of uveal melanomas in relation to various morphological features.

Methods: Nine consecutive eyes enucleated for uveal melanoma were examined by transscleral spectroscopy, using a fiber-optic probe that exerted a fixed pressure on the scleral surface. Spectroscopic measurements, covering the wavelength range of 400-1100 nm, were sequentially performed over the uveal melanoma and on the opposite (normal) side of each eye.

Dietary vitamin D3 supplements reduce demyelination in the cuprizone model.

Vitamin D is emerging as a probably important environmental risk factor in multiple sclerosis, affecting both susceptibility and disease progression. It is not known to what extent this effect is due to a modulation of peripheral lymphocyte function, or to intrathecal effects of vitamin D. We investigated the effect of dietary vitamin D3 content on de/remyelination in the cuprizone model, which is a well established toxic model of demyelination, with no associated lymphocyte infiltration.

Microtubule-severing ATPase spastin in glioblastoma: increased expression in human glioblastoma cell lines and inverse roles in cell motility and proliferation.

We studied the expression and distribution of the microtubule-severing enzyme spastin in 3 human glioblastoma cell lines (U87MG, U138MG, and T98G) and in clinical tissue samples representative of all grades of diffuse astrocytic gliomas (n = 45). In adult human brains, spastin was distributed predominantly in neuronsand neuropil puncta and, to a lesser extent, in glia. Compared with normal mature brain tissues, spastin expression and cellular distribution were increased in neoplastic glial phenotypes, especiallyin glioblastoma (p < 0.

Global gene expression profiling and tissue microarray reveal novel candidate genes and down-regulation of the tumor suppressor gene CAV1 in sporadic vestibular schwannomas.

Background: The vestibular nerve is the predilection site for schwannomas. Few transcriptomic studies have been performed on solely sporadic vestibular schwannomas (VSs).

Objective: To detect genes with altered expression levels in sporadic VSs.

Progressive multifocal leucoencephalopathy in an immunocompetent patient with favourable outcome. A case report.

Background: To report the clinical course of PML in an apparently immunocompetent patient treated with cidofovir.

Case Presentation: A 35-year-old immunocompetent man who developed progressive hemianopsia, aphasia, and limb weakness underwent repeated MRI scans of the brain, spinal fluid analyses, and brain biopsy. Before diagnosis was established based on brain biopsy, he was consecutively treated with methylprednisolone, acyclovir, ceftriaxone and plasmapheresis, but he deteriorated rapidly suggestive of the immune reconstitution inflammatory syndrome (IRIS).

Localized cerebral energy failure in DNA polymerase gamma-associated encephalopathy syndromes.

Mutations in the catalytic subunit of the mitochondrial DNA-polymerase gamma cause a wide spectrum of clinical disease ranging from infantile hepato-encephalopathy to juvenile/adult-onset spinocerebellar ataxia and late onset progressive external ophthalmoplegia. Several of these syndromes are associated with an encephalopathy that characteristically shows episodes of rapid neurological deterioration and the development of acute cerebral lesions. The purpose of this study was to investigate the nature, distribution and natural evolution of central nervous system lesions in polymerase gamma associated encephalopathy focusing particularly on lesions identified by magnetic resonance imaging.

A salmon based diet protects mice from behavioural changes in the cuprizone model for demyelination.

Background & Aims: Although many patients with multiple sclerosis (MS) use special diets, the data available at present are insufficient to assess any potential benefit of diet modification. Cuprizone induced demyelination is a commonly used animal model for demyelination in the central nervous system.

Methods: The present study was designed to analyse behaviour and activity due to demyelination in mice fed with 0.

Effects of dietary intervention on MRI activity, de- and remyelination in the cuprizone model for demyelination.

Whether differences in diet composition may influence demyelinating diseases remains controversial. The aim of this study was to analyse if diets with a different composition of polyunsaturated fatty acids (PUFAs) could influence demyelination and remyelination in cuprizone fed mice, a widely used animal model for de- and remyelination. C57Bl/6 mice were fed with 0.

Ependymal tumors with sarcomatous change ("ependymosarcoma"): a clinicopathologic and molecular cytogenetic study.

Gliosarcomas are uncommon primary tumors of the central nervous system defined as exhibiting both glial and sarcomatous components. Sarcomatous change occurring in ependymal tumors is rare. We identified 11 such examples.

mtDNA nt13708A variant increases the risk of multiple sclerosis.

Background: Mitochondrial DNA (mtDNA) polymorphism is a possible factor contributing to the maternal parent-of-origin effect in multiple sclerosis (MS) susceptibility.

Methods And Findings: In order to investigate the role of mtDNA variations in MS, we investigated six European MS case-control cohorts comprising >5,000 individuals. Three well matched cohorts were genotyped with seven common, potentially functional mtDNA single nucleotide polymorphisms (SNPs).

Panel review of anaplastic oligodendroglioma from European Organization For Research and Treatment of Cancer Trial 26951: assessment of consensus in diagnosis, influence of 1p/19q loss, and correlations with outcome.

The diagnosis of anaplastic oligodendroglioma (AOD) or anaplastic oligoastrocytoma (AOA) is subject to interobserver variation. The aim of this study was to estimate consensus in typing and grading of these tumors using tumor material collected in a large prospective randomized phase III study and to correlate the consensus diagnosis with the 1p/19q status of the tumors and the clinical outcome. The available pathology material of the first 150 patients, randomized into the European Organization for Research and Treatment of Cancer Trial 26951, was reviewed by an independent panel of 9 neuropathologists.

Pigmented astrocytoma with suprasellar location: case report and literature review.

A large suprasellar, partly cystic, contrast-enhancing tumor was resected from a 19-year-old woman who presented with bitemporal visual field defects and reduced visual acuity. Grossly, the tumor was brown and located in the subarachnoid space. Histologically, it was composed of spindle and pleomorphic cells, including giant tumor cells, with markedly pleomorphic nuclei.

Class III beta-tubulin isotype: a key cytoskeletal protein at the crossroads of developmental neurobiology and tumor neuropathology.

The expression of the cytoskeletal protein class III beta-tubulin isotype is reviewed in the context of human central nervous system development and neoplasia. Compared to systemic organs and tissues, class III beta-tubulin is abundant in the brain, where it is prominently expressed during fetal and postnatal development. As exemplified in cerebellar neurogenesis, the distribution of class III beta-tubulin is neuron associated, exhibiting different temporospatial gradients in the neuronal progeny of the external granule layer versus the neuroepithelial germinal matrix of the velum medullare.

Subpial demyelination in the cerebral cortex of multiple sclerosis patients.

The extent and pattern of demyelination in the cerebral cortex was determined in 78 tissue blocks from the brains of 20 multiple sclerosis (MS) patients and 28 tissue blocks from 7 patients without neurological disease. Tissue blocks from 4 predetermined areas (cingulate gyrus, frontal, parietal, and temporal lobe) were studied, irrespective of macroscopically evident MS plaques. All tissue blocks contained cerebral cortex and periventricular and/or subcortical white matter.

Class III beta-tubulin in human development and cancer.

The differential cellular expression of class III beta-tubulin isotype (betaIII) is reviewed in the context of human embryological development and neoplasia. As compared to somatic organs and tissues, betaIII is abundant in the central and peripheral nervous systems (CNS and PNS) where it is prominently expressed during fetal and postnatal development. As exemplified in cerebellar and sympathoadrenal neurogenesis, the distribution of betaIII is neuron-associated, exhibiting distinct temporospatial gradients according to the regional neuroepithelia of origin.

On the neuronal/neuroblastic nature of medulloblastomas: a tribute to Pio del Rio Hortega and Moises Polak.

The concept that medulloblastomas represent cerebellar neuroblastic tumours was championed by del Rio Hortega in the 1930s and was critically reappraised in the 1960s by Moises Polak. Whereas the aetiology and molecular pathogenesis of medulloblastomas remain unresolved, there is now compelling evidence in support of a fundamentally neuronal tumour phenotype. Tumour cells express in a differentiation-dependent manner a repertoire of neuronal cytoskeletal, synaptic, and other lineage-associated proteins.

Localization of the neuronal class III beta-tubulin in oligodendrogliomas: comparison with Ki-67 proliferative index and 1p/19q status.

The class III beta-tubulin isotype (betaIII) is widely regarded as a neuronal marker in development and neoplasia. Whereas the expression of betaIII in neuronal/neuroblastic tumors is differentiation-dependent, the aberrant expression of this cytoskeletal protein in astrocytomas is associated with an ascending gradient of malignancy. To test the generality of this observation we have compared the immunoreactivity (IR) profiles of the betaIII isotype with the Ki-67 nuclear antigen proliferative index in 41 archival, surgically excised oligodendrogliomas (32 classical [WHO grade II] and 9 anaplastic [WHO grade III]).