Therapeutic perspectives of high pulse repetition rate electroporation.

Electroporation, a technique that uses electrical pulses to temporarily or permanently destabilize cell membranes, is increasingly used in cancer treatment, gene therapy, and cardiac tissue ablation. Although the technique is efficient, patients report discomfort and pain. Current strategies that aim to minimize pain and muscle contraction rely on the use of pharmacological agents.

Pharmacological Characterization of [F]-FNM and Evaluation of NMDA Receptors Activation in a Rat Brain Injury Model.

Purpose: NMDA receptors (NMDARs) dysfunction plays a central role in the physiopathology of psychiatric and neurodegenerative disorders whose mechanisms are still poorly understood. The development of a PET (positron emission tomography) tracer able to selectively bind to the NMDARs intra-channel PCP site may make it possible to visualize NMDARs in an open and active state. We describe the in vitro pharmacological characterization of [F]-fluoroethylnormemantine ([F]-FNM) and evaluate its ability to localize activated NMDA receptors in a rat preclinical model of excitotoxicity.

Sphingosine 1-Phosphate Receptor 5 (S1P5) Deficiency Promotes Proliferation and Immortalization of Mouse Embryonic Fibroblasts.

Sphingosine 1-phosphate (S1P), a bioactive lipid, interacts with five widely expressed G protein-coupled receptors (S1P1-5), regulating a variety of downstream signaling pathways with overlapping but also opposing functions. To date, data regarding the role of S1P5 in cell proliferation are ambiguous, and its role in controlling the growth of untransformed cells remains to be fully elucidated. In this study, we examined the effects of S1P5 deficiency on mouse embryonic fibroblasts (MEFs).

Sphingosine Kinase-1 Is Overexpressed and Correlates with Hypoxia in Osteosarcoma: Relationship with Clinicopathological Parameters.

The Sphingosine kinase-1/Sphingosine 1-Phosphate (SphK1/S1P) signaling pathway is overexpressed in various cancers, and is instrumental for the adaptation to hypoxia in a number of solid tumor models, but no data are available in osteosarcoma. Here we report that SphK1 and the S1P receptor are involved in HIF-1α accumulation in hypoxic osteosarcoma cells. FTY720 (Fingolimod), which targets SphK1 and S1P prevented HIF-1α accumulation, and also inhibited cell proliferation in both normoxia and hypoxia unlike conventional chemotherapy.