Calcium (Ca2+) signaling and the modulation of intracellular calcium ([Ca2+]i) levels play critical roles in several key processes that regulate cellular survival, growth, differentiation, metabolism, and death in normal cells. On the other hand, aberrant Ca2+-signaling and loss of [Ca2+]i homeostasis contributes to tumor initiation proliferation, angiogenesis, and other key processes that support tumor progression in several different cancers. Currently, chemically and functionally distinct drugs are used as chemotherapeutic agents in the treatment and management of cancer among which certain anti-cancer drugs reportedly suppress pro-survival signals and activate pro-apoptotic signaling through modulation of Ca2+-signaling-dependent mechanisms. Most importantly, the modulation of [Ca2+]i levels via the endoplasmic reticulum-mitochondrial axis and corresponding action of channels and pumps within the plasma membrane play an important role in the survival and death of cancer cells. The endoplasmic reticulum-mitochondrial axis is of prime importance when considering Ca2+-signaling-dependent anti-cancer drug targets. This review discusses how calcium signaling is targeted by anti-cancer drugs and highlights the role of calcium signaling in epigenetic modification and the Warburg effect in tumorigenesis.

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INTRODUCTION: Patients with rheumatoid arthritis (RA) have shorter life expectancy and their risk of cardiovascular death is more than 50 % higher than the rest of the population. Early myocardial dysfunction in RA patients may be detectable sooner using speckle-tracking echocardiography. METHOD: Cross-sectional study enrolled 55 patients with RA (mean age 44.1 years) without known cardiovascular disease and 31 healthy controls. All subjects underwent a standard echocardiographic examination: indexed left ventricular mass, left ventricle ejection fraction, isovolumic contraction and relaxation times (IVCT and IVRT), mitral valve infl ow curve (E/A), septal mitral annular motion (e'), and E/e' ratio as well as the speckle tracking assessment of left ventricle longitudinal, radial and circular strain and strain rate. (-19.51 % vs -21.46 %, p=0.049). Radial, circular, and transversal strains and strain rates were same in both groups. Global longitudinal epicardial strain correlated with IVCT and IVRT, disease duration, and markers of myocardial damage NTproBNP. CONCLUSIONS: Standard echocardiographic assessment of myocardial function is examiner-and angle-dependent method with considerable limitations for evaluation of minimal subclinical changes. Speckle-tracking echocardiography signifi cantly revealed incipient myocardial dysfunction in RA patients without overt cardiovascular diseases. This correlates with clinical RA characteristics and markers of cardiac damage (Tab. 4, Ref. 48). Text in PDF www.elis.sk.

Background In contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity. Methods and results CLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure. Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest. Conclusion In patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes. ClinicalTrials identifier ISRCTN43070564