Clinical performance evaluation of the Idylla NRAS-BRAF mutation test on retrospectively collected formalin-fixed paraffin-embedded colorectal cancer tissue.

Aims: Understanding the molecular mechanisms of underlying disease has led to a movement away from the one-drug-fits-all paradigm towards treatment tailored to the genetic profile of the patient. The Biocartis Idylla platform is a novel fully automated, real-time PCR-based diagnostic system. The Idylla NRAS-BRAF mutation test has been developed for the qualitative detection of mutations in and oncogenes, facilitating genetic profiling of patients with cancer.

Thrombin activatable fibrinolysis inhibitor: a putative target to enhance fibrinolysis.

Thrombin activatable fibrinolysis inhibitor (TAFI) was discovered two decades ago consequent to the identification of an unstable carboxypeptidase (CPU) formed upon thrombin activation of its proenzyme. The antifibrinolytic effects of the activated form (TAFIa, CPU) are linked with its capacity to remove C-terminal lysines from the surface of the fibrin clot. A distinctive characteristic of TAFIa is its temperature-dependent conformational instability: TAFIa activity spontaneously decays with an apparent half-life of 8 to 15 minutes at 37°C.

Identification and characterisation of monoclonal antibodies that impair the activation of human thrombin activatable fibrinolysis inhibitor through different mechanisms.

Thrombin activatable fibrinolysis inhibitor (TAFI) forms a molecular link between coagulation and fibrinolysis and is a putative target to develop profibrinolytic drugs. Out of a panel of monoclonal antibodies (MA) raised against TAFI-ACIIYQ, we selected MA-TCK11A9, MA-TCK22G2 and MA-TCK27A4, which revealed high affinity towards human TAFI-TI-wt. MA-TCK11A9 was able to inhibit mainly plasmin-mediated TAFI activation, MA-TCK22G2 inhibited plasmin- and thrombin-mediated TAFI activation and MA-TCK27A4 inhibited TAFI activation by plasmin, thrombin and thrombin/thrombomodulin (T/TM) in a dose-dependent manner.

Evaluation of the profibrinolytic properties of an anti-TAFI monoclonal antibody in a mouse thromboembolism model.

The enhancement of fibrinolysis constitutes a promising approach to treat thrombotic diseases. Activated thrombin activatable fibrinolysis inhibitor (TAFIa) attenuates fibrinolysis and is an attractive target to develop profibrinolytic drugs. TAFI can be activated by thrombin, thrombin/thrombomodulin, or plasmin, but the in vivo physiologic TAFI activator(s) are unknown.