Mise au point de la quantification des progéniteurs endothéliaux circulants par cytométrie en flux (application au suivi de l'angiogenèse dans le cancer)

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Etude pilote ENDOMAG sur les complications vasculaires chez les patients traités par allogreffe de cellules souches hématopoïétiques

Les patients bénéficiant d une allogreffe de cellules souches hématopoïetiques (CSH) sont sujet à de graves complications infectieuses opportunistes, immunologiques (GvHD) oui vasculaires. Maladie veino-occlusive (MVO), microangiopathie thrombotique (MAT) et syndrome de fuite capillaire (SFC) représentent les principaux syndromes d atteinte vasculaire décrits dans cette population. Leur diagnostic, qui devrait être précoce, reste difficile en l absence de marqueur biologique spécifique. L étude prospective multicentrique ENDOMAG a pour objectif principal de déterminer si les cellules endothéliales circulantes (CEC) peuvent constituer un marqueur prédictif de la survenue de complications vasculaires chez le patients allogreffé. Les CEC sont un marqueur sensible et spécifique d atteinte vasculaire dans de nombreuses pathologies cardiovasculaires, auto-immunes ou néoplasiques. Selon nos résultats, le taux de CEC avant conditionnement, ainsi que son évolution jusqu en période post-greffe précoce permettrait la discrimination des patients allogreffés à risque de développer certaines complications vasculaires (SFC). Son utilisation en tant que marqueur supplémentaire diagnostique ou de suivi de complications vasculaires pourrait être envisagée. En effet, leur diagnostic fait appel à des signes cliniques et des paramètres biologiques peu spécifiques. A l inverse, ce marqueur, ne nous semble pas utile via à vis des autres complications rencontrées chez l allogreffé. Enfin, nous n avons pas identifié de nouveau paramètre susceptible d influencer le taux de CEC dans cette population.CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Recherche de causes de thromboses dans l'hémoglobulinurie paroxystique nocturne

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Rôle de la sous-unité d'intégrine alpha6 dans l'angiogènese et la vasculogènese

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Recherches de marqueurs biologiques associés à la survenue de séquelles après un épisode symptomatique d'embolie pulmonaire

PARIS-BIUP (751062107) / SudocSudocFranceF

Effect of fucoidan on fibroblast growth factor-2-induced angiogenesis in vitro

Fucoidans are sulfated polysaccharides extracted from brown marine algae. A purified fucoidan fraction exhibits the same venous antithrombotic activity as heparin in rabbits, but with a lower anticoagulant effect. Because of its heparin-like structure, we postulated that fucoidan might modulate heparin-binding angiogenic growth factor activity. We thus studied its effect, at antithrombotic concentrations, on fibroblast growth factor (FGF)-2-induced proliferation and differentiation of human umbilical vein endothelial cells. The fucoidan effect on endothelial cell differentiation was evaluated by studying the expression of surface proteins (i.e. integrin, adhesion molecule) known to be modulated by FGF-2 and involved in angiogenesis, and by quantifying closed areas delimited by vascular tubes formed on reconstituted basement membrane. Fucoidan had no modulatory effect on the mitogenic activity of FGF-2, but significantly increased tubular structure density induced by FGF-2. Fucoidan alone increased α6 integrin subunit expression with only partially organized tubular structure. In the presence of FGF-2, fucoidan enhanced α6, β1 and PECAM-1 and inhibited αvβ3 integrin expression. Heparin had no effect in these systems. The most striking effect of fucoidan was observed on α6 expression and tube formation was abolished by monoclonal anti-α6 antibodies. Fucoidan plus FGF-2 effect on α6 expression was markedly decreased by monoclonal anti-FGF-2 antibodies, indicating that fucoidan acts mainly via FGF-2. These results show that, at antithrombotic concentrations, contrary to heparin, fucoidan can enhance vascular tube formation induced by FGF-2 with a modulation of the expression of surface proteins (mainly α6) involved in angiogenesis

Recent Advances in Anticoagulant Treatment of Immune Thrombosis: A Focus on Direct Oral Anticoagulants in Heparin-Induced Thrombocytopenia and Anti-Phospholipid Syndrome

For more than 10 years, direct oral anticoagulants (DOACs) have been increasingly prescribed for the prevention and treatment of thrombotic events. However, their use in immunothrombotic disorders, namely heparin-induced thrombocytopenia (HIT) and antiphospholipid syndrome (APS), is still under investigation. The prothrombotic state resulting from the autoimmune mechanism, multicellular activation, and platelet count decrease, constitutes similarities between HIT and APS. Moreover, they both share the complexity of the biological diagnosis. Current treatment of HIT firstly relies on parenteral non-heparin therapies, but DOACs have been included in American and French guidelines for a few years, providing the advantage of limiting the need for treatment monitoring. In APS, vitamin K antagonists are conversely the main treatment (+/− anti-platelet agents), and the use of DOACs is either subject to precautionary recommendations or is not recommended in severe APS. While some randomized controlled trials have been conducted regarding the use of DOACs in APS, only retrospective studies have examined HIT. In addition, vaccine-induced immune thrombotic thrombocytopenia (VITT) is now a part of immunothrombotic disorders, and guidelines have been created concerning an anticoagulant strategy in this case. This literature review aims to summarize available data on HIT, APS, and VITT treatments and define the use of DOACs in therapeutic strategies

Renal Carcinoma and Angiogenesis: Therapeutic Target and Biomarkers of Response in Current Therapies

Due to the aberrant hypervascularization and the high immune infiltration of renal tumours, current therapeutic regimens of renal cell carcinoma (RCC) target angiogenic or immunosuppressive pathways or both. Tumour angiogenesis plays an essential role in tumour growth and immunosuppression. Indeed, the aberrant vasculature promotes hypoxia and can also exert immunosuppressive functions. In addition, pro-angiogenic factors, including VEGF-A, have an immunosuppressive action on immune cells. Despite the progress of treatments in RCC, there are still non responders or acquired resistance. Currently, no biomarkers are used in clinical practice to guide the choice between the different available treatments. Considering the role of angiogenesis in RCC, angiogenesis-related markers are interesting candidates. They have been studied in the response to antiangiogenic drugs (AA) and show interest in predicting the response. They have been less studied in immunotherapy alone or combined with AA. In this review, we will discuss the role of angiogenesis in tumour growth and immune escape and the place of angiogenesis-targeted biomarkers to predict response to current therapies in RCC

Increased VEGFR2 expression during human late endothelial progenitor cells expansion enhances in vitro angiogenesis with up-regulation of integrin α 6

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