A polysialic acid mimetic peptide promotes functional recovery in a mouse model of spinal cord injury

International audienc

Polysialic acid neural cell adhesion molecule (PSA-NCAM) is an adverse prognosis factor in glioblastoma, and regulates olig2 expression in glioma cell lines

International audienceBackground: Glioblastoma multiforme (GBM) is the most aggressive and frequent brain tumor, albeit without cure. Although patient survival is limited to one year on average, significant variability in outcome is observed. The assessment of biomarkers is needed to gain better knowledge of this type of tumor, help prognosis, design and evaluate therapies. The neurodevelopmental polysialic acid neural cell adhesion molecule (PSA-NCAM) protein is overexpressed in various cancers. Here, we studied its expression in GBM and evaluated its prognosis value for overall survival (OS) and disease free survival (DFS).Methods: We set up a specific and sensitive enzyme linked immunosorbent assay (ELISA) test for PSA-NCAM quantification, which correlated well with PSA-NCAM semi quantitative analysis by immunohistochemistry, and thus provides an accurate quantitative measurement of PSA-NCAM content for the 56 GBM biopsies analyzed. For statistics, the Spearman correlation coefficient was used to evaluate the consistency between the immunohistochemistry and ELISA data. Patients' survival was estimated by using the Kaplan-Meier method, and curves were compared using the log-rank test. On multivariate analysis, the effect of potential risk factors on the DFS and OS were evaluated using the cox regression proportional hazard models. The threshold for statistical significance was p = 0.05.Results: We showed that PSA-NCAM was expressed by approximately two thirds of the GBM at variable levels. On univariate analysis, PSA-NCAM content was an adverse prognosis factor for both OS (p = 0.04) and DFS (p = 0.0017). On multivariate analysis, PSA-NCAM expression was an independent negative predictor of OS (p = 0.046) and DFS (p = 0.007). Furthermore, in glioma cell lines, PSA-NCAM level expression was correlated to the one of olig2, a transcription factor required for gliomagenesis.Conclusion: PSA-NCAM represents a valuable biomarker for the prognosis of GBM patients

Efficacy of a novel endotoxin adsorber polyvinylidene fluoride fiber immobilized with l-serine ligand on septic pigs*

A novel adsorber, polyvinylidene fluoride matrix immobilized with l-serine ligand (PVDF-Ser), was developed in the present study to evaluate its safety and therapeutic efficacy in septic pigs by extracorporeal hemoperfusion. Endotoxin adsorption efficiency (EAE) of the adsorber was firstly measured in vitro. The biocompatibility and hemodynamic changes during extracorporeal circulation were then evaluated. One half of 16 pigs receiving lipopolysaccharide (Escherichia coli O111:B4, 5 μg/kg) intravenously in 1 h were consecutively treated by hemoperfusion with the new adsorber for 2 h. The changes of circulating endotoxin and certain cytokines and respiratory function were analyzed. The 72 h-survival rate was assessed eventually. EAE reached 46.3% (100 EU/ml in 80 ml calf serum) after 2 h-circulation. No deleterious effect was observed within the process. The plasma endotoxin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were decreased during the hemoperfusion. Arterial oxygenation was also improved during and after the process. Furthermore, the survival time was significantly extended (>72 h vs. 47.5 h for median survival time). The novel product PVDF-Ser could adsorb endotoxin with high safety and efficacy. Early use of extracorporeal hemoperfusion with the new adsorber could reduce the levels of circulating endotoxin, IL-6, and TNF-α, besides improve respiratory function and consequent 72 h-survival rate of the septic pigs. Endotoxin removal strategy with blood purification using the new adsorber renders a potential promising future in sepsis therapy