Hemostatic System in Malignancy: Providing the “Soil” in Metastatic Niche Formation

Malignancy arises and progresses in tight association with changes in the tumor microenvironment and deregulation of hemostatic system. Cancer induces hemostatic imbalance through production and secretion of procoagulant substances, suppression of anticoagulant mechanisms, endothelial activation, and angiogenic switch. Cancer cells are equipped with certain coagulation signaling receptors such as tissue factor (TF) and urokinase plasminogen activator receptor (uPAR). Tissue factor: as major initiator of coagulation, TF is considered the main cause for hypercoagulability in cancer. Constitutive TF expression by cancer cells is a hallmark of malignancy rendering tumors proangiogenic and prometastatic. TF fosters metastasis through coagulation-dependent pathways leading to fibrin deposition in the evolving premetastatic niche. TF has been identified as an independent predictor for metastatic development and adverse prognosis. uPAR: Tissue overexpression of uPAR is demonstrated in almost all human cancers and is associated with advanced disease. Increased uPAR expression is driven by molecular events involving K-ras and SRC oncogenes. Transactivation of these receptors, mediated by binding to hemostatic proteins, activates intracellular signaling pathways, modulates gene expression and facilitates processes of tumor initiation, epithelial-to-mesenchymal transition, anoikis, and metastasis. By manipulating hemostatic processes, tumor induces tolerant host environment necessary for evasion of defense attacks, survival, and progression

Acute Poisoning with Dapsone and Olanzapine: Severe Methemoglobinemia and Coma with a Favourable Outcome / Острое Отравление Медикаментами Dapsone И Olanzapine: Тяжёлая Метгемоглобинемия И Кома С Благоприятным Исходом

Дапсон является лекарством, которое обычно применяется для лечения проказы (лепры). В Европе его предписывают в редких случаях, прежде всего для лечения некоторых кожных заболеваний, напр. dermatitis herpetiformis. Отравления Дапсоном тоже исключительно редки, поэтому информация о них представляет интерес для токсикологической практики. Здесь мы описываем случай острого отравления Даксоном, единственный в серии из 21 000 случаев острых отравлений, лечение которых проводилось в клинике клинической токсикологии Университетской больницы „Св. Георги” ЕАД, Пловдив, Болгария в течение периода 1999 - 2013 г