Jean-Paul Issartel

The transcriptomic response of mixed neuron-glial cell cultures to 1,25-dihydroxyvitamin d3 includes genes limiting the progression of neurodegenerative diseases.

Seasonal or chronic vitamin D deficiency and/or insufficiency is highly prevalent in the human population. Receptors for 1,25-dihydroxyvitamin D3, the hormonal metabolite of vitamin D, are found throughout the brain. To provide further information on the role of this hormone on brain function, we analyzed the transcriptomic profiles of mixed neuron-glial cell cultures in response to 1,25-dihydroxyvitamin D3. 1,25-dihydroxyvitamin D3 treatment increases the mRNA levels of 27 genes by at least 1.9 fold. Among them, 17 genes were related to neurodegenerative and psychiatric diseases, or brain morphogenesis. Notably, 10 of these genes encode proteins potentially limiting the progression of Alzheimers disease. These data provide support for a role of 1,25-dihydroxyvitamin D3 in brain disease prevention. The possible consequences of circannual or chronic vitamin D insufficiencies on a tissue with a low regenerative potential such as the brain should be considered.

The heterogeneity of meningioma revealed by multiparameter analysis: infiltrative and non-infiltrative clinical phenotypes

Tumor invasion or infiltration of adjacent tissues is the source of clinical challenges in diagnosis as well as prevention and treatment. Among brain tumors, infiltration of the adjacent tissues with diverse pleiotropic mechanisms is frequently encountered in benign meningiomas. We assessed whether a multiparametric analysis of meningiomas based on data from both clinical observations and molecular analyses could provide a consistent and accurate appraisal of invasive and infiltrative phenotypes and help determine the diagnosis of these tumors. Tissue analyses of 37 meningiomas combined enzyme-linked immunosorbent assay (ELISA) and surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) assays of two different protein biomarkers (thrombospondin 1 and a phosphorylated form of vimentin) as well as gene expression analyses with oligonucleotide micro-arrays. Up to four different clinical and molecular parameters were then examined for tumor classification. From this study, we were able to cluster 36 out of the 37 tumors into two different subsets corresponding to infiltrative/invasive and non-infiltrative tumors. In addition, meningiomas that invade brain and those that infiltrate the neighboring skull bone exhibited no distinguishable molecular features. Our multi-parameter analysis that combines clinical data, transcriptomic and molecular assays clearly reveals the heterogeneity of meningiomas and distinguishes the intrinsically infiltrative/invasive tumors from the non-infiltrative meningiomas.

Comparative proteomic profiles of Aspergillus fumigatus and Aspergillus lentulus strains by surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS)

BackgroundSurface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) was applied to analyze the protein profiles in both somatic and metabolic extracts of Aspergillus species. The study was carried out on some Aspergillus species within the Fumigati section (Aspergillus fumigatus wild-types and natural abnormally pigmented mutants, and Aspergillus lentulus). The aim was to validate whether mass spectrometry protein profiles can be used as specific signatures to discriminate different Aspergillus species or even mutants within the same species.ResultsThe growth conditions and the SELDI-TOF parameters were determined to generate characteristic protein profiles of somatic and metabolic extracts of Aspergillus fumigatus strains using five different ProteinChips®, eight growth conditions combining two temperatures, two media and two oxygenation conditions. Nine strains were investigated: three wild-types and four natural abnormally pigmented mutant strains of A. fumigatus and two strains of A. lentulus. A total of 242 fungal extracts were prepared. The spectra obtained are protein signatures linked to the physiological states of fungal strains depending on culture conditions. The best resolutions were obtained using the chromatographic surfaces CM10, NP20 and H50 with fractions of fungi grown on modified Sabouraud medium at 37°C in static condition. Under these conditions, the SELDI-TOF analysis allowed A. fumigatus and A. lentulus strains to be grouped into distinct clusters.ConclusionsSELDI-TOF analysis distinguishes A. fumigatus from A. lentulus strains and moreover, permits separate clusters of natural abnormally pigmented A. fumigatus strains to be obtained. In addition, this methodology allowed us to point out fungal components specifically produced by a wild-type strain or natural mutants. It offers attractive potential for further studies of the Aspergillus biology or pathogenesis.

MicroRNA-Based Drugs for Brain Tumors

MicroRNAs (miRNAs) are key regulatory elements encoded by the genome. A single miRNA can downregulate the expression of multiple genes involved in diverse functions. Because cancer is a disease with multiple gene aberrations, developing novel approaches to identify and modulate miRNA pathways may result in a breakthrough for cancer treatment. With a special focus on glioblastoma (GBM), this review provides an up-to-date summary of miRNA biogenesis, the role of miRNA in cancer resistance, and essential tools for modulating miRNA expression, as well as of clinically promising RNAi delivery systems and how they can be adapted for therapy.