Institute of Pathological Physiology

Prague, Czech Republic

Institute of Pathological Physiology

Prague, Czech Republic
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Kriska M.,Institute of Pharmacology and Clinical Pharmacology | Gajdoslk J.,Ambulatory Praxis | Dukat A.,University Hospital Bratislava | Bernadic M.,Institute of Pathological Physiology
Farmaceuticky Obzor | Year: 2016

Pharmacotherapy rating standardized quality indicators are still not available. Indirect evaluation is the topic of frequent discussions, commonly without relevant conclusions. Relevant results are often missing, and it seems that the bias of optimal results and healthy ammonut of criticism is an invincible barrier. If we refer to the issue from the point of entire society and human actions, pharmacological failure occurs in medicine more frequently than in technical disciplines mainly because of high variability of biological system reactions and changes in human body. Increasing of pharmacotherapeutical safety requires implementation of preventive programs to recognize and monitor negative interactions. These programs have to involve all participants in pharmacovigilancy, firstly medical proffesionals, doctors, farmaceuts, but also patients.


Molinsky J.,Institute of Pathological Physiology | Molinsky J.,General University Hospital | Klanova M.,Institute of Pathological Physiology | Klanova M.,General University Hospital | And 14 more authors.
Leukemia and Lymphoma | Year: 2013

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand with selective antitumor activity. However, many primary tumors are TRAIL resistant. Previous studies reported that roscovitine, a cyclin-dependent kinase inhibitor, sensitized various solid cancer cells to TRAIL. We show that roscovitine and TRAIL demonstrate synergistic cytotoxicity in hematologic malignant cell lines and primary cells. Pretreatment of TRAIL-resistant leukemia cells with roscovitine induced enhanced cleavage of death-inducing signaling complex-bound proximal caspases after exposure to TRAIL. We observed increased levels of both pro-and antiapoptotic BCL-2 proteins at the mitochondria following exposure to roscovitine. These results suggest that roscovitine induces priming of cancer cells for death by binding antiapoptotic BCL-2 proteins to proapoptotic BH3-only proteins at the mitochondria, thereby decreasing the threshold for diverse proapoptotic stimuli. We propose that the mitochondrial priming and enhanced processing of apical caspases represent major molecular mechanisms of roscovitine-induced sensitization to TRAIL in leukemia/lymphoma cells. © 2012 Informa UK, Ltd.

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