THE EVOLUTION OF FUNDAMENTAL RIGHTS PROTECTION WITHIN THE EU LEGAL ORDER

The issue of fundamental rights protection in the European Union is of highestimportance. The discussion on the topic has been started as early as the beginning of 1970s,although the founding Treaties did not include any catalogue of fundamental rights. After along evolutionary process with many actors involved, the final result is shown in the Treaty ofLisbon

European Union Accession to the European Convention on Human Rights: An Institutional “Marriage”

A possible accession of European Union (hereinafter: EU/the Union) to the European Convention on Human Rights (ECHR/the Convention) has been discussed in legal society for more than thirty years. The topic had widely opened after the 1979 Commission Memorandum where the major pros and cons were underlined and practical problems were addressed. This discussion led to an official request to the European Court of Justice (ECJ/the Court) in relation to the legality of such accession; the outcome was included in opinion 2/94 that found such accession incompatible with the European Community (EC/the Community) Treaty. © Konstantinos G. Margaritis. All rights reserved. This paper may be freely circulated in electronic or hard copy provided it is not modified in any way, the rights of the author not infringed, and the paper is not quoted or cited without express permission of the author. The editors cannot guarantee a stable URL for any paper posted here, nor will they be responsible for notifying others if the URL is changed or the paper is taken off the site. Electronic copies of this paper may not be posted on any other website without express permission of the author

Loss of miR-378 in prostate cancer, a common regulator of KLK2 and KLK4, correlates with aggressive disease phenotype and predicts the short-term relapse of the patients

A large number of prostate cancer (PCa) patients receive treatment without significant benefits, strengthening the need for accurate prognosis, which can be supported by the study of miRNAs. In silico specificity analysis was performed for the identification of miRNAs able to regulate KLK2 and KLK4 expression. Total RNA was extracted from prostate tissues obtained from PCa and benign prostate hyperplasia patients. Thereafter, RNA was polyadenylated and reverse transcribed to cDNA, which was used for qPCR analysis. miR-378 was predicted to target both KLK2 and KLK4 and downregulated levels detected in PCa patients (p = 0.050). The reduction of miR-378 was correlated with higher Gleason score (p = 0.018), larger diameter tumors (p = 0.034), and elevated serum PSA (p = 0.006). Regarding prognosis, miR-378 was able to improve risk stratification according to Gleason score or tumor stage, while higher risk to recur highlighted for the patients expressing lower miR-378 levels. Finally, the loss of miR-378 was able to predict the short-term relapse of ‘high’- and ‘very high’- recurrence-risk patients, independent of Gleason score, tumor stage, PSA, and age as indicated by Kaplan-Meier survival curves (p = 0.030) and multivariate Cox regression analysis (p = 0.018). In conclusion, loss of miR-378 expression increases the risk for PCa progression and relapse, despite active treatment

Targeting kallikrein-related peptidases in prostate cancer

Introduction: Novel therapeutic compounds are needed for prostate cancer (CaP), given the limitations of already used drugs and the disease’s mortality, often attributed to castrate resistance. Tissue kallikrein and kallikrein-related peptidases (KLKs) form a family of serine proteases aberrantly expressed and broadly implicated in human malignancies. In CaP, KLKs participate in the promotion of cell proliferation, extracellular matrix degradation, tumour cell invasion and metastasis. Areas covered: This review discusses the different ways of inhibiting, modulating and exploiting KLK activity and/or expression as emerging CaP therapeutics. KLKs are targeted by diverse naturally occurring substances, including proteinaceous inhibitors, low-molecular-weight peptides and Zn2+. Synthetic KLK inhibitors include protein/peptide-based inhibitors and small molecules. A re-engineered serpin-based KLK inhibitor is under evaluation in first-in-human trials as a CaP therapeutic, whereas additional potent and selective KLK inhibitors with relevance to CaP have been synthesized. KLK3-activated pro-drugs have entered Phase I and Phase II clinical trials as therapeutics for prostate tumours. The KLK3-based PROSTVAC vaccine is evaluated in Phase III clinical trials. Targeting KLK expression via RNA interference methods could represent another promising therapeutic approach for CaP. Expert opinion: Apart from their immense biomarker potential, KLKs also hold promise as the basis of novel CaP therapeutics