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Specific inhibition of CAIX activity enhanced the effect of tumor irradiation and might, therefore, be an attractive strategy to improve overall cancer treatment.

Introduction: Several studies reported on the humoral response in subjects having received the BNT162b2 mRNA COVID-19 vaccine. However, data on the kinetics of antibodies 3 months postvaccination are currently lacking and are important to drive the future vaccination strategy. Methods:The CRO-VAX HCP study is an ongoing multicenter, prospective and interventional study designed to assess the antibody response in a population of healthcare professionals who had received two doses of the BNT162b2 mRNA COVID-19 vaccine. Two-hundred individuals underwent a blood drawn within 2 days before the first vaccine dose. One-hundred and forty-two persons (71%)were categorized as seronegative at baseline while 58 (29%) were seropositive. Samples were then collected after 14, 28, 42, 56, and 90 days. Antibodies against the SARS-CoV-2 nucleocapsid and the receptor binding domain of the S1 subunit of the spike protein were measured in all individuals at different time points.Results: Using a one-compartment kinetics model, the time to maximum concentration was estimated at 36 ± 3 days after the first dose and the estimated half-life of antibodies was 55 days (95% CI: 37-107 days) in seronegative participants. In seropositive participants, the time to maximum concentration was estimated at 24 ± 4 days and the estimated half-life was 80 days (95% CI: 46-303 days). The antibody response was higher in seropositive compared to seronegative participants. Conclusion:In both seropositive and seronegative subjects, a significant antibody decline was observed at 3 months compared to the peak response. Nevertheless, the humoral response remained robust in all participants.

Blood coagulation starts immediately after damage to the vascular endothelium. This system is essential for minimizing blood loss from an injured blood vessel but also contributes to vascular thrombosis. Although it has long been thought that the intrinsic coagulation pathway is not important for clotting in vivo, recent data obtained with genetically altered mice indicate that contact phase proteins seem to be essential for thrombus formation. We show that recombinant Ixodes ricinus contact phase inhibitor (Ir-CPI), a Kunitz-type protein expressed by the salivary glands of the tick Ixodes ricinus, specifically interacts with activated human contact phase factors (FXIIa, FXIa, and kallikrein) and prolongs the activated partial thromboplastin time (aPTT) in vitro. The effects of Ir-CPI were also examined in vivo using both venous and arterial thrombosis models. Intravenous administration of Ir-CPI in rats and mice caused a dose-dependent reduction in venous thrombus formation and revealed a defect in the formation of arterial occlusive thrombi. Moreover, mice injected with Ir-CPI are protected against collagen- and epinephrine-induced thromboembolism. Remarkably, the effective antithrombotic dose of Ir-CPI did not promote bleeding or impair blood coagulation parameters. To conclude, our results show that a contact phase inhibitor is an effective and safe antithrombotic agent in vivo.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder of the hematopoietic stem cell that makes blood cells more sensitive to the action of complement. Patients experience intravascular hemolysis, smooth muscle dystonia, renal failure, arterial and pulmonary hypertension, recurrent infectious diseases and an increased risk of notably dreadful thrombotic complications. The diagnosis is made by flow cytometry. Efforts have been recently performed to improve the sensitivity and the standardization of this technique. PNH is frequently associated with aplastic anemia or low-risk myelodysplasia and may be asymptomatic. Management of the classical form of PNH has been dramatically revolutionized by the development of eculizumab, which brings benefits in terms of hemolysis, quality of life, renal function, thrombotic risk, and life expectancy. Prophylaxis and treatment of arterial and venous thrombosis currently remain a challenge in PNH.

Dasatinib, nilotinib, and ponatinib increase vascular occlusive events. New-generation TKIs improve MMR but not the overall survival at 1 year in patients with CML.

This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. AbstractBackground: Thrombin generation testing has been used to provide information on the coagulation phenotype of patients. The most used technique is the calibrated automated thrombogram (CAT) but it suffers from a lack of standardization, preventing its implementation in routine. The ST Genesia is a new analyzer designed to assess thrombin generation based on the same principle as the CAT. Unlike the CAT system, the ST Genesia is a benchtop, fully automated analyzer, able to perform the analyses individually and not by batch, with strict control of variables such as temperature and volumes, ensuring, theoretically, maximal reproducibility. Objectives:This study aimed at assessing the performance of the STG-DrugScreen application on the ST Genesia analyzer. We also aimed at exploring stability of plasma samples after freezing and defining a reference normal range. Results:Results demonstrated the excellent interexperiment precision of the ST Genesia and confirmed that the use of a reference plasma helps reducing the