Predictions for the future of kallikrein-related peptidases in molecular diagnostics

Kallikrein-related peptidases (KLKs) form a cancer-related ensemble of serine proteases. This multigene family hosts the most widely used cancer biomarker that is PSA-KLK3, with millions of tests performed annually worldwide. The present report provides an overview of the biomarker potential of the extended KLK family (KLK1-KLK15) in various disease settings and envisages approaches that could lead to additional KLK-driven applications in future molecular diagnostics. Particular focus is given on the inclusion of KLKs into multifaceted cancer biomarker panels that provide enhanced diagnostic, prognostic and/or predictive accuracy in several human malignancies. Such panels have been described so far for prostate, ovarian, lung and colorectal cancers. The role of KLKs as biomarkers in non-malignant disease settings, such as Alzheimer’s disease and multiple sclerosis, is also commented upon. Predictions are given on the challenges and future directions regarding clinically oriented KLK research

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

On the origin of Euphorbia subg. Esula in Europe (Euphorbiaceae)

A study of the taxonomy and chorology of the Bulgarian species of Euphorbia has led me to consider their phytogeography; this entailed a closer view on the main features of florogenesis and distribution of subg. Esula in Europe. There are two problems concerned, viz. the origin of the two sections Tulocarpa (Raf.) Prokh. and Murtekias Prokh. which contain the most primitive and ancient species of the subg. Esula and furthermore a consideration of their mutual relationships and the main trends of their evolution within the subgenus. The data on the distribution of the species examined in the present paper have been taken from the works of Boissier (1862, 1879), Halacsy (1904), Fiori (1925), Hegi (1925), Hayek (1927), Eig (1932), Prokhanov (1933, 1949), Ade & Rechinger (1938), Rechinger (1938,1943, 1952, 1960), Czeczott (1939), Losa Espagna (1946), Diapoulis (1948), Prodan (1953), Vindt (1953), and Köie & Rechinger (1954/55)

Acute myocardial infarction due to the left main coronary artery occlusion: Electrocardiographic patterns, angiographic findings, revascularization and in-hospital outcomes

AbstractBackgroundPrimary angioplasty improves outcomes of acute myocardial infarction (AMI). However, in the highest risk subgroups, the mortality remains high despite modern catheter-based reperfusion therapy. This study analyzed patients with AMI caused by the left main coronary artery unstable lesion, a subgroup considered to be associated with very high early mortality.MethodsA multicenter registry enrolled 6742 consecutive patients with AMI. Ninety-seven patients (1,4% of the entire study population) had left main as the infarct related artery. Baseline clinical characteristics, ECG patterns, coronary angiographic and echocardiographic data were correlated with the revascularization therapies used and with in-hospital outcomes.ResultsTwenty-five patients (25,8%) died during the hospital stay. The deceased patients were older, had more freqently bundle branch block on the admission ECG, had higher Killip class on presentation, more frequently had TIMI flow <3 and PCI success rate was 72% (vs. 100% among survivors). Left main coronary artery (LMCA) lesion impaired distal flow (TIMI flow 0–2 on presentation) in 35 patients: the most frequent ECG presentation pattern for these LMCA occlusions was ST segment elevation (n=17), followed by RBBB (n=9; with LAH 6 and without LAH 3), LBBB (n=6) and ST segment depression (n=3). In other words: acute LMCA occlusion presents in 51% with ECG changes other than ST segment elevations. Patients with TIMI flow 0–2 had higher Killip class on admission, lower ejection fraction and higher in-hospital mortality (37% vs. 20%), when compared to those with TIMI flow 3 on the initial angiogram.ConclusionsDespite modern interventional therapy, acute myocardial infarction caused by the left main coronary artery obstruction bears high early mortality. The presence of bundle branch block, diminished TIMI flow on the initial angiogram, higher age and Killip class are related with increased mortality