Bevacizumab dose adjustment to improve clinical outcomes of glioblastoma.

BACKGROUND: Glioblastoma (GBM) is one of the most aggressive and vascularized brain tumors in adults, with a median survival of 20.9 months. In newly diagnosed and recurrent GBM, bevacizumab demonstrated an increase in progression-free survival, but not in overall survival. METHODS: We conducted an in silico analysis of VEGF expression, in a cohort of 1082 glioma patients. Then, to determine whether appropriate bevacizumab dose adjustment could increase the anti-angiogenic response, we used in vitro and in vivo GBM models. Additionally, we analyzed VEGFA expression in tissue, serum, and plasma in a cohort of GBM patients before and during bevacizumab treatment. RESULTS: We identified that 20% of primary GBM did not express VEGFA suggesting that these patients would probably not respond to bevacizumab therapy as we proved in vitro and in vivo. We found that a specific dose of bevacizumab calculated based on VEGFA expression levels increases the response to treatment in cell culture and serum samples from mice bearing GBM tumors. Additionally, in a cohort of GBM patients, we observed a correlation of VEGFA levels in serum, but not in plasma, with bevacizumab treatment performance. CONCLUSIONS: Our data suggest that bevacizumab dose adjustment could improve clinical outcomes in Glioblastoma treatment.

Polyethylene glycol improves current methods for circulating extracellular vesicle-derived DNA isolation.

BACKGROUND: Extracellular vesicles (EVs) are small membrane-bound vesicles which play an important role in cell-to-cell communication. Their molecular cargo analysis is presented as a new source for biomarker detection, and it might provide an alternative to traditional solid biopsies. However, the most effective approach for EV isolation is not yet well established. RESULTS: Here, we study the efficiency of the most common EV isolation methods-ultracentrifugation, Polyethlyene glycol and two commercial kits, Exoquick® and PureExo®. We isolated circulating EVs from the bloodstream of healthy donors, characterized the size and yield of EVs and analyzed their protein profiles and concentration. Moreover, we have used for the first time Digital-PCR to identify and detect specific gDNA sequences, which has several implications for diagnostic and monitoring many types of diseases. CONCLUSIONS: Our findings present Polyethylene glycol precipitation as the most feasible and less cost-consuming EV isolation technique.

Persistence and variation in microstructural design during the evolution of spider silk.

The extraordinary mechanical performance of spider dragline silk is explained by its highly ordered microstructure and results from the sequences of its constituent proteins. This optimized microstructural organization simultaneously achieves high tensile strength and strain at breaking by taking advantage of weak molecular interactions. However, elucidating how the original design evolved over the 400 million year history of spider silk, and identifying the basic relationships between microstructural details and performance have proven difficult tasks. Here we show that the analysis of maximum supercontracted single spider silk fibers using X ray diffraction shows a complex picture of silk evolution where some key microstructural features are conserved phylogenetically while others show substantial variation even among closely related species. This new understanding helps elucidate which microstructural features need to be copied in order to produce the next generation of biomimetic silk fibers.

Identification and dynamics of polyglycine II nanocrystals in Argiope trifasciata flagelliform silk.

Spider silks combine a significant number of desirable characteristics in one material, including large tensile strength and strain at breaking, biocompatibility, and the possibility of tailoring their properties. Major ampullate gland silk (MAS) is the most studied silk and their properties are explained by a double lattice of hydrogen bonds and elastomeric protein chains linked to polyalanine ß-nanocrystals. However, many basic details regarding the relationship between composition, microstructure and properties in silks are still lacking. Here we show that this relationship can be traced in flagelliform silk (Flag) spun by Argiope trifasciata spiders after identifying a phase consisting of polyglycine II nanocrystals. The presence of this phase is consistent with the dominant presence of the -GGX- and -GPG- motifs in its sequence. In contrast to the passive role assigned to polyalanine nanocrystals in MAS, polyglycine II nanocrystals can undergo growing/collapse processes that contribute to increase toughness and justify the ability of Flag to supercontract.