MCAM and its Isoforms as Novel Targets in Angiogenesis Research and Therapy

Melanoma cell adhesion molecule (MCAM) (CD146) is a membrane glycoprotein of the mucin family. It is one of the numerous proteins composing the junction of the vascular endothelium, and it is expressed in other cell types such as cancer cells, smooth muscle cells, and pericytes. Some recent works were designed to highlight its structural features, its location in the endothelium, and its role in angiogenesis, vascular permeability, and monocyte transmigration, but also in the maintenance of endothelial junctions and tumor development. MCAM exists in different splice variants and is shedded from the vascular membrane by metalloproteases. Studies about MCAM spliced and cleaved variant on human angiogenic physiological and pathological models permit a better understanding on the roles initially described for this protein. Furthermore, this knowledge will help in the future to develop therapeutic and diagnostic tools targeting specifically the different MCAM variant. Recent advances in research on angiogenesis and in the implication of MCAM in this process are discussed in this chapter

MCAM/MUC18/CD146 as a multifaceted warning marker of melanoma progression in liquid biopsy

Human malignant melanoma shows a high rate of mortality after metastasization, and its incidence is continuously rising worldwide. Several studies have suggested that MCAM/MUC18/CD146 plays an important role in the progression of this malignant disease. MCAM/MUC18/CD146 is a typical single-spanning transmembrane glycoprotein, existing as two membrane isoforms, long and short, and an additional soluble form, sCD146. We previously documented that molecular MCAM/MUC18/CD146 expression is strongly associated with disease progression. Recently, we showed that MCAM/MUC18/CD146 and ABCB5 can serve as melanoma-specific-targets in the selection of highly primitive circulating melanoma cells, and constitute putative proteins associated with disease spreading progression. Here, we analyzed CD146 molecular expression at onset or at disease recurrence in an enlarged melanoma case series. For some patients, we also performed the time courses of molecular monitoring. Moreover, we explored the role of soluble CD146 in different cohorts of melanoma patients at onset or disease progression, rather than in clinical remission, undergoing immune therapy or free from any clinical treatment. We showed that MCAM/MUC18/CD146 can be considered as: (1) a membrane antigen suitable for identification and enrichment in melanoma liquid biopsy; (2) a highly effective molecular "warning " marker for minimal residual disease monitoring; and (3) a soluble protein index of inflammation and putative response to therapeutic treatments

Regulation du transport de sodium par l'aldosterone: influence de la concentration intracellulaire de sodium sur la Na-K-ATPase dans le tubule collecteur cortical de rein de lapin

SIGLEINIST T 73231 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Élaboration d'une méthodologie d'analyse foncière reproductible sur une sélection de gares de l'agglomération lyonnaise

This urban master thesis has for aim to elaborate the first part of a reproducible methodology analyze (concerning the cartographic and reglementary analyze) concerning a perimeter of train stations selection. This thesis rely on first of all a short history of French train stations evolution. The goal is to understand why these equipments became today a centrality for public and private actors who are looking for urban project opportunities promoting social and urban development. Secondly, on the analyze of different methodologies from public studies but also on reflection concerning a building project implementation which are the skeleton to elaborate a reproducible methodology. To check the success of its implementation, this methodology has been applied on a selection of zones around train stations allowing also to determinate its reproducibility and at the end of this thesis, its evaluation.Ce mémoire de master 2 en urbanisme a pour objectif d’élaborer la première partie d’une méthodologie d’analyse foncière reproductible (à savoir l’analyse cartographique et règlementaire) sur un périmètre autour d’une sélection de gares ferroviaires. Pour ce faire, celui-ci s’est appuyé dans un premier temps sur un court historique de l’évolution des gares ferroviaires en France. Le but étant de comprendre pourquoi ces équipements sont devenus aujourd’hui une centralité pour les acteurs publics ou privés qui cherchent à réaliser des projets d’aménagements induisant un développement social et urbain. Dans un deuxième temps, sur l’analyse de différentes méthodologies issues d’études publiques mais également de réflexions concernant la mise en oeuvre d’un projet immobilier qui ont constitué le squelette pour élaborer cette méthodologie reproductible. Enfin, pour vérifier le succès de sa mise en oeuvre, cette méthodologie a été par la suite appliquée sur une sélection de zones autour des gares permettant également de déterminer sa reproductibilité mais aussi à la fin de ce mémoire, son évaluation

Contribution à l'étude du rôle de CD146 soluble dans langiogenèse et de l'effet du blocage du récepteur P2Y12 sur la lésion endothéliale lors d'une angioplastie coronaire

Nous avons montré que la molécule recombinante humaine CD146 soluble (rh-sCD146) a un effet chimiotactique et angiogénique sur les cellules dérivées de progéniteurs endothéliaux (PEC) en augmentant leur capacité à migrer, à proliférer et à former des pseudo-capillaires. Des expériences réalisées in vivo sur un modèle d'ischémie de la patte chez le rat ont montré que des injections locales répétées de rh-sCD146 permettent une diminution significative du taux d'auto-amputation des animaux et une augmentation du taux de perfusion sanguin de la patte et de la densité capillaire. Dans une 2ème partie du travail, nous avons montré que l'angioplastie coronaire induit une hausse significative du nombre de cellules endothéliales circulantes (CEC) 6h après l'intervention (H6). Les lésions endothéliales, évaluées par la mesure de la variation du nombre de CEC (H6-H0), sont plus élevées chez les non-répondeurs par rapport aux bons répondeurs au Clopidogrel et sont corrélées à l'index VASPWe showed that the recombinant human soluble CD146 (rh-sCD146) has a chemotactic and angiogenic effect on endothelial progenitor derived cells (EPC) by increasing their ability to migrate, to proliferate and to form pseudo- capillaries. In an in vivo experiments model of ischemia in the rat by femoral artery ligation we showed that repeated local injections of rh-sCD146 for 12 days allows a significant reduction in the rate of animals self-amputation and an increase in the rate of blood perfusion of the leg and in the capillary density. In a second part of the work, we have shown that percutaneous coronary intervention induced a significant rise in circulating endothelial cells (CEC) levels 6h after the procedure (H6). The endothelial injury, assessed by CEC delta-change between H6 and H0, was significantly higher in the high on-treatment platelet reactivity group compared with the good responders to Clopidogrel and correlated with the Vasodilatator-Stimulated Phosphoprotein indexAIX-MARSEILLE2-Bib.electronique (130559901) / SudocSudocFranceF

Vasopressin potentiates mineralocorticoid selectivity by stimulating 11 beta hydroxysteroid deshydrogenase in rat collecting duct.

Arginine vasopressin (AVP) and corticosteroid hormones are involved in sodium reabsorption regulation in the renal collecting duct. Synergy between AVP and aldosterone has been well documented, although its mechanism remains unclear. Both aldosterone and glucocorticoid hormones bind to the mineralocorticoid receptor (MR), and mineralocorticoid selectivity depends on the MR-protecting enzyme 11 beta hydroxysteroid deshydrogenase (11-HSD), which metabolizes glucocorticoids into derivatives with low affinity for MR. We have investigated whether the activity of 11-HSD could be influenced by AVP and corticosteroid hormones. This study shows that in isolated rat renal collecting ducts, AVP increases 11-HSD catalytic activity. This effect is maximal at 10(-8) M AVP (a concentration clearly above the normal physiological range of AVP concentrations) and involves the V2 receptor pathway, while activation of protein kinase C or changes in intracellular calcium are ineffective. The stimulatory effect of AVP on 11-HSD is largely reduced after adrenalectomy, and is selectively restored by infusion of aldosterone, not glucocorticoids. We conclude that this synergy between AVP and aldosterone in controlling the activity of 11-HSD is likely to play a pivotal role in resetting mineralocorticoid selectivity, and hence sodium reabsorption capacities of the renal collecting duct