Metabolism and epigenetics of pancreatic cancer stem cells.

Pancreatic Cancer (PDA) is an aggressive malignancy characterized by early spread and a high mortality. Current studies suggest that a subpopulation of cells exist within tumors, cancer stem cell (CSC), which are capable of self-renewal and give rise to unique progeny which form the major neoplastic cellular component of tumors. While CSCs constitute a small cellular subpopulation within the tumor, their resistance to chemotherapy and radiation make them an important therapeutic target for eradication. Along with distinctive phenotypic properties, CSCs possess a unique metabolic plasticity allowing them to rapidly respond and adapt to environmental changes. These cells and their progeny also display a significantly altered epigenetic state with distinctive patterns of DNA methylation. Several mechanisms of cross-talk between epigenetic and metabolic pathways in PDA exist which ultimately contribute to the observed cellular plasticity and enhanced tumorigenesis. In this review we discuss various examples of this metabolic-epigenetic interplay and how it may constitute a new avenue for therapy specifically targeting CSCs in PDA.

The effect of selected pre-analytical phase variables on plasma thromboxane A2 measurements in humans.

AIMS: Platelet function testing is often affected by the existence of different pre-analytical variables that can cause platelet activation. The aim of this study was to assess the effect of such variables that are present when samples are taken (different anticoagulants, incubation temperature, and storage conditions) to select those which enable to reach optimal range of measured plasma concentrations of the two stable thromboxane A2 metabolites, that is, thromboxane B2 (TxB2) and 11-dehydrothromboxane B2 (11-dTxB2). MATERIALS AND METHODS: For the purpose of this study, whole blood samples obtained from 20 volunteers were screened for TxB2 and 11-dTxB2 concentrations using commercial EIA kits (Cayman Chemicals™; Neogen™) in relation to the effect of different anticoagulants, using different incubation temperatures and storage conditions. RESULTS: Trisodium citrate has been shown not to be affecting the TxB2 and 11-dTxB2 concentrations compared with the values measured in the serum. Incubation of the samples for 1 h at 37 °C and freezing at -20 °C or -80 °C give the most suitable concentration range of both thromboxanes in the used EIA measurement. CONCLUSION: This study describes the setup of such pre-analytical phase conditions that enable the screening of platelet function in terms of the plasma concentrations of TxB2 and 11-dTxB2 in selected EIA measurement.

Multicentre randomized trial comparing transport to primary angioplasty vs immediate thrombolysis vs combined strategy for patients with acute myocardial infarction presenting to a community hospital without a catheterization laboratory. The PRAGUE study.

BACKGROUND: Primary coronary angioplasty is an effective reperfusion strategy in acute myocardial infarction. However, its availability is limited, and transporting patients to an angioplasty centre in the acute phase of myocardial infarction has not yet been proved safe. METHODS: The PRAGUE study (PRimary Angioplasty in patients transferred from General community hospitals to specialized PTCA Units with or without Emergency thrombolysis) compared three reperfusion strategies in patients with acute myocardial infarction, presenting within 6 h of symptom onset at community hospitals without a catheterization laboratory: group A - thrombolytic therapy in community hospitals (n=99), group B - thrombolytic therapy during transportation to angioplasty (n=100), group C - immediate transportation for primary angioplasty without pre-treatment with thrombolysis (n=101). RESULTS: No complications occurred during transportation in group C. Two ventricular fibrillations occurred during transportation in group B. Median admission-reperfusion time in transported patients (group B 106 min, group C 96 min) compared favourably with the anticipated >90 min in group A. The combined primary end-point (death/reinfarction/stroke at 30 days) was less frequent in group C (8%) compared to groups B (15%) and A (23%, P<0. 02). The incidence of reinfarction was markedly reduced by transport to primary angioplasty (1% in group C vs 7% in group B vs 10% in group A, P<0.03). CONCLUSIONS: Transferring patients from community hospitals to a tertiary angioplasty centre in the acute phase of myocardial infarction is feasible and safe. This strategy is associated with a significant reduction in the incidence of reinfarction and the combined clinical end-point of death/reinfarction/stroke at 30 days when compared to standard thrombolytic therapy at the community hospital.