Monkey PLAU/uPA (Urokinase-type plasminogen Activator) ELISA Kit

Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder associated with reduced platelet counts and a unique gain-of-function defect in fibrinolysis due to increased expression and storage of urokinase plasminogen activator (uPA) by megakaryocytes. QPD increases risks for bleeding and its key clinical feature is delayed-onset bleeding, following surgery, dental procedures or trauma, which responds only to treatment with fibrinolytic inhibitors. The genetic cause of the disorder is a tandem duplication mutation of the uPA gene, PLAU, which upregulates uPA expression in megakaryocytes by an unknown mechanism. The increased platelet stores of uPA trigger plasmin-mediated degradation of QPD alpha-granule proteins. The gain-of-function defect in fibrinolysis is thought to be central to the pathogenesis of QPD bleeding as the activation of QPD platelets leads to release of uPA from alpha-granules and accelerated clot lysis. The purpose of this review is to summarize current knowledge on QPD pathogenesis and the recommended approaches to QPD diagnosis and treatment.

Dapper homolog 1 alpha (DACT1 alpha) is a member of DACT family and an important regulator in the planar cell polarity pathway. We aim to clarify its functional role in metastasis ability of gastric cancer. DACT1 alpha was silenced in all gastric cancer cell lines (8/8), but expressed in normal gastric tissue. Ectopic expression of DACT1 alpha in silenced gastric cancer cell lines (AGS, BGC823 and MGC803) by stable transfection significantly suppressed cancer cell spreading (P < 0.05), migration (P < 0.01) and invasion (P < 0.01). These effects were associated with downregulation of planar cell polarity pathway related genes involved in cell proliferation (PDGFB, VEGFA), adhesion (ITGA1, ITGA2, ITGA3, ITGB3) and migration/invasion (PLAU, MMP9, MCAM, Dvl-2 and JNK). DACT1 alpha promoter methylation was detected in 205 gastric cancers and 20 normal controls by direct bisulfite genomic sequencing. DACT1 alpha methylation was detected in 29.3% (60/205) of gastric cancer patients, but not in normal tissues. DACT1 alpha methylation was associated with poor survival of gastric cancer patients. In conclusion, DACT1 alpha plays a pivotal role as a potential tumor suppressor in migration and invasion of gastric cancer. DACT1 alpha methylation may serve as a biomarker for the prognosis of gastric cancer.