Search

Glioblastoma (GBM) possesses glioma stem cells (GSCs) that exhibit aggressive invasion behavior in the brain. Current preclinical GBM invasion assays using mouse brain xenografts are time consuming and less efficient. Here, we demonstrate an array of methods that allow rapid and efficient assaying of GSCs invasion in human brain organoids. The assays are versatile to characterize various aspects of GSCs, such as invasion, integration, and interaction with mature neurons of brain organoids. Tissue clearing and quantitative 3D imaging of GSCs in host organoids reveal that invasiveness is inversely correlated with the organoids' age. Importantly, the described invasion assays can distinguish the invasive behaviors of primary and recurrent GSCs. The assays are also amenable to test pharmacological agents. As an example, we show that GI254023X, an inhibitor of ADAM10, could prevent the integration of GSCs into the organoids.

Microbial biofilms are known to support a number of human infections, including those related to medical devices. This work is focused on the development of novel dual-function amphiphilic random copolymers to be employed as coatings for medical devices. Particularly, copolymers were obtained by polymerization of an antimicrobial cationic monomer (bearing tertiary amine) and an antioxidant and antimicrobial hydrophobic monomer (containing hydroxytyrosol, HTy). To obtain copolymers with various amphiphilic balance, different molar ratios of the two monomers were used. 1H NMR and DSC analyses evidenced that HTy aromatic rings are able to interact with each other leading to a supra-macromolecular re-arrangement and decrease the copolymer size in water. All copolymers showed good antioxidant activity and Fe2+ chelating ability. Cytotoxicity and hemolytic tests evidenced that the amphiphilic balance, cationic charge density and polymer size in solution are key determinants for polymer biocompatibility. As for the antimicrobial properties, the lowest minimal inhibitory concentration (MIC = 40 μg/mL) against Staphylococcus epidermidis was shown by the water-soluble copolymer having the highest HTy molar content (0.3). This copolymer layered onto catheter surfaces was also able to prevent staphylococcal adhesion. This approach permits not only prevention of biofilm infections but also reduction of the risk of emergence of drug-resistant bacteria. Indeed, the combination of two active compounds in the same polymer can provide a synergistic action against biofilms and suppress reactive species oxygen (ROS), known to promote the occurrence of antibiotic resistance. © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Purpose Glioblastoma multiforme (GBM) is the most aggressive brain tumor. The cancer stem cell hypothesis postulates the existence within GBM of a small fraction of self-renewing cells with stem like properties (GSCs), resistant to conventional treatments. Metabolic profiling may contribute to discover new diagnostic or prognostic biomarkers to be used for personalized therapies. Methods Forty-four GSC lines, derived from GBM patients were analyzed via MR spectroscopy as described in [1] . Unsupervised Cluster analysis of MR data was performed to identify GSC subgroups with different metabolic profiles. Responses to treatment with oligomycin and etomoxir were examined by MRS and confocal microscopy. Results Clustering of GSCs evidenced three subgroups: Clusters 1a and 1b, with high intergroup similarity and neural fingerprints, and Cluster 2, with a metabolism typical of commercial tumor lines (Fig. 1) according to [2] . Subclones generated by the same GSC line showed different metabolic phenotypes. Aerobic glycolysis prevailed in Cluster 2 cells as demonstrated by higher lactate production compared to Cluster 1 cells. Oligomycin, a mitochondrial ATPase inhibitor, induced high lactate extrusion only in Cluster 1 cells, where it produced neutral lipid accumulation detected as mobile lipid signals (MRS) and as lipid droplets (confocal microscopy). Conclusions These results indicate a relevant role of mitochondrial fatty acids oxidation for energy production in GSCs. On the other hand, further metabolic differences, likely accounting for different therapy responsiveness observed after etomoxir treatment, suggest that caution must be used in considering patient treatment with mitochondria FAO blockers.