Background: Adenosine is a nucleoside that impacts the cardiovascular system during cardiovascular or inflammatory diseases. The rapid determination of adenosine in blood may be useful in emergency medicine especially in syncope diagnose or septic shock. We compare its measurement in blood using fixed potential amperometry (FPA), with usual methods: mass spectrometry (LC-MS/MS) or high performance liquid chromatography (HPLC). Methods:Twenty healthy subjects (14 men and 6 women) and ten patients suffering from vasovagal syncope (VVS, 6 women and 4 men) were included. Blood samples were collected by vein puncture for plasma adenosine assay and in the same time using finger puncture for direct FAP measurement and on blotting paper for LC-MS/MS. Results:Mean plasma adenosine concentration was 26% higher using HPLC compared with LC-MSMS; p<0.01. In whole blood, adenosine concentration was 35% higher using FPA compared with LC-MS/MS. We found a good correlation between adenosine values measured by FAP and LC-MS/MS in whole blood and between LC-MS/MS and HPLC in plasma. Mean adenosine concentration was higher in patients whatever the method used. Conclusion:Adenosine measurement to the patient's bed, using FPA may be useful in some cases where high adenosine is associated with pejorative outcome.

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Lower proportion of CD19 þ IL-10 þ and CD19 þ CD24 þ CD27 þ but not CD1d þ CD5 þ CD19 þ CD24 þ CD27 þ IL-10 þ B cells in children with autoimmune thyroid diseases

Enzalutamide (MDV3100) is a potent second-generation androgen receptor antagonist approved for the treatment of castration-resistant prostate cancer (CRPC) in chemotherapy-na€ ve as well as in patients previously exposed to chemotherapy. However, resistance to enzalutamide and enzalutamide withdrawal syndrome have been reported. Thus, reliable and integrated preclinical models are required to elucidate the mechanisms of resistance and to assess therapeutic settings that may delay or prevent the onset of resistance. In this study, the prostate cancer multistage murine model TRAMP and TRAMP-derived cells have been used to extensively characterize in vitro and in vivo the response and resistance to enzalutamide. The therapeutic profile as well as the resistance onset were characterized and a multiscale stochastic mathematical model was proposed to link the in vitro and in vivo evolution of prostate cancer. The model showed that all therapeutic strategies that use enzalutamide result in the onset of resistance. The model also showed that combination therapies can delay the onset of resistance to enzalutamide, and in the best scenario, can eliminate the disease. These results set the basis for the exploitation of this "TRAMPbased platform" to test novel therapeutic approaches and build further mathematical models of combination therapies to treat prostate cancer and CRPC.Significance: Merging mathematical modeling with experimental data, this study presents the "TRAMP-based platform" as a novel experimental tool to study the in vitro and in vivo evolution of prostate cancer resistance to enzalutamide.

A better understanding of the complex crosstalk among key receptors and signaling pathways involved in cancer progression is needed to improve current therapies. We have investigated in cell models representative of the major subtypes of breast cancer (BC) the interplay between the chemokine CXCL12/CXCR4/ACKR3 and EGF receptor (EGFR) family signaling cascades. These cell lines display a high heterogeneity in expression profiles of CXCR4/ACKR3 chemokine receptors, with a predominant intracellular localization and different proportions of cell surface CXCR4+, ACKR3+ or double-positive cell subpopulations, and display an overall modest activation of oncogenic pathways in response to exogenous CXCL12 alone. Interestingly, we find that in MDA-MB-361 (luminal B subtype, Her2-overexpressing), but not in MCF7 (luminal A) or MDA-MB-231 (triple negative) cells, CXCR4/ACKR3 and EGFR receptor families share signaling components and crosstalk mechanisms to concurrently promote ERK1/2 activation, with a key involvement of the G protein-coupled receptor kinase 2 (GRK2) signaling hub and the cytosolic tyrosine kinase Src. Our findings suggest that in certain BC subtypes, a relevant cooperation between CXCR4/ACKR3 and growth factor receptors takes place to integrate concurrent signals emanating from the tumor microenvironment and foster cancer progression.