Prognostic and predictive biomarkers in prostate cancer

Prostate cancer (PCa) is one of the leading causes of cancer death among males, especially in more developed countries. Diagnosis is often achieved at an early stage of the disease with prostate biopsy, following a screening test showing elevated serum levels of prostate-specific antigen or a positive digital rectal examination. Early detection of PCa has led to a substantial decline in the number of metastatic patients. However, the prostate-specific antigen screening test has proved to be a double-edged sword so far, as it also accounts for PCa overdiagnosis. Due to the variability of PCa features, accurate prognosis of PCa patients is very important for determining treatment options. Therefore, this review focuses on the most promising prognostic and predictive biomarkers in PCa, which are likely to play a pivotal role, alone or in panels, in the personalized medicine era that has recently emerged

Advanced glycation end-products induce endoplasmic reticulum stress in human aortic endothelial cells

Background: Advanced glycation end products (AGEs), the final products of the Maillard reaction, have been shown to impair endothelial proliferation and function, thus contributing to endothelial cell injury present in diabetes, inflammatory and cardiovascular diseases. Endoplasmic reticulum (ER) stress triggered under hyperglycemic, hypoxic and oxidative conditions has been implicated in endothelial dysfunction through activation of the unfolded protein response (UPR). The present study investigates the role of AGEs in ER stress induction in human aortic endothelial cells exposed to variable AGE treatments. Methods: Human aortic endothelial cells (HAEC) were treated with increasing concentrations (100, 200 μg/mL) of AGE-bovine serum albumin (AGE-BSA) at different time-points (24, 48, 72 h). The induction of ER stress and the involved UPR components were investigated on mRNA and protein levels. Apoptosis was quantitatively determined by flow cytometry detecting propidium iodide expression and annexin V binding simultaneously. Results: AGEs administration significantly reduced HAEC proliferation in a time- and dose-dependent manner. An immediate induction of the ER chaperones GRP78, GRP94 and the transcriptional activator, XBP-1 was observed at 24 h and 48 h. A later induction of the phospho-lF2α and proapoptotic transcription factor CHOP was observed at 48 h and 72 h, being correlated with elevated early apoptotic cell numbers at the same time-points. Conclusions: The present study demonstrates that AGEs directly induce ER stress in human aortic endothelial cells, playing an important role in endothelial cell apoptosis. Targeting AGEs signaling pathways in order to alleviate ER stress may prove of therapeutic potential to endothelial dysfunction-related disorders

Transcriptional regulation of endothelin-1 expression by advanced glycation end-products in human aortic endothelium is mediated via NF-kappaΒ and AP-1

Advanced Glycation End-products (AGEs) are produced by the non-enzymatic glycation of proteins, lipids and nucleic acids, resulting in an overload of highly reactive molecules of endogenous or exogenous (dietary) origin. Increased AGE levels in circulation and concomitant elevated tissue deposition have been associated with diabetic complications, atheromatosis, ageing and more recently with polycystic ovary syndrome pathogenesis. Interaction of AGEs with their receptor RAGE (Receptor for AGEs) activates intracellular signaling pathways which induce targeted gene expression in endothelium including upregulation of cell adhesion molecules and endothelin-1 (ET-1), implicated in vascular injury and endothelial dysfunction. The purpose of this study is to explore the molecular mechanism of AGE-induced regulation of ET-1 gene/protein expression in human endothelial cells and investigate its functional relevance in normal rat vascular endothelium

Marine Renewable Energy Clustering in the Mediterranean Sea: The Case of PELAGOS Project

The main ideas presented in this work are an outcome of the Interreg MED project PELAGOS (Promoting innovative nEtworks and cLusters for mArine renewable energy synerGies in Mediterranean cOasts and iSlands). Since Blue Energy development is at its very beginning in the Mediterranean Sea, the aim of the paper is to present and discuss in depth the key-issues for a Marine Renewable Energy (MRE) cluster development in the Mediterranean and reveal its necessity for the commercial and sustainable development of Blue Energy in the area. This cluster is expected to stimulate the relevant Blue Energy sectors under the perspective of smart and sustainable growth. A healthy cluster is based on an efficient cluster policy. The main policy constituents (innovation, legislation and financial frameworks) are discussed taking into account the interrelated characteristics that are expected to specify the commercial development of MRE in the area. Key issues that can contribute to the establishment and acceleration of deployment of the related technological innovation are identified, and existent hindrances and challenges encountered in MRE sector are determined. The importance of solid financing instruments and strong collaborations among interested stakeholders is also highlighted for the viability of the MRE cluster. Finally, as an example of the cluster activities at a national level, the Greek Hub for Blue Energy is introduced. In this respect, aspects in terms of its structure and the services provided to its members are analyzed

The role of CXC-chemokine receptor CXCR2 and suppressor of cytokine signaling-3 (SOCS-3) in renal cell carcinoma

BACKGROUND: Chemokine receptor signaling pathways are implicated in the pathobiology of renal cell carcinoma (RCC). However, the clinical relevance of CXCR2 receptor, mediating the effects of all angiogenic chemokines, remains unclear. SOCS (suppressor of cytokine signaling)-3 is a negative regulator of cytokine-driven responses, contributing to interferon-α resistance commonly used to treat advanced RCC with limited information regarding its expression in RCC. METHODS: In this study, CXCR2 and SOCS-3 were immunohistochemically investigated in 118 RCC cases in relation to interleukin (IL)-6 and (IL)-8, their downstream transducer phosphorylated (p-)STAT-3, and VEGF expression, being further correlated with microvascular characteristics, clinicopathological features and survival. In 30 cases relationships with hypoxia-inducible factors, i.e. HIF-1a, p53 and NF-κΒ (p65/RelA) were also examined. Validation of immunohistochemistry and further investigation of downstream transducers, p-JAK2 and p-c-Jun were evaluated by Western immunoblotting in 5 cases. RESULTS: Both CXCR2 and IL-8 were expressed by the neoplastic cells their levels being interrelated. CXCR2 strongly correlated with the levels of HIF-1a, p53 and p65/RelA in the neoplastic cells. Although SOCS-3 was simultaneously expressed with p-STAT-3, its levels tended to show an inverse relationship with p-JAK-2 and p-c-Jun in Western blots and were positively correlated with HIF-1a, p53 and p65/p65/RelA expression. Neither CXCR2 nor SOCS-3 correlated with the extent of microvascular network. IL-8 and CXCR2 expression was associated with high grade, advanced stage and the presence/number of metastases but only CXCR2 adversely affected survival in univariate analysis. Elevated SOCS-3 expression was associated with progression, the presence/number of metastasis and shortened survival in both univariate and multivariate analysis. CONCLUSIONS: Our findings implicate SOCS-3 overexpression in RCC metastasis and biologic aggressiveness advocating its therapeutic targeting. IL-8/CXCR2 signaling also contributes to the metastatic phenotype of RCC cells but appears of lesser prognostic utility. Both CXCR2 and SOCS-3 appear to be related to transcription factors induced under hypoxia

Fully Integrated Electronic-Biophotonic System-on-Chip for Real-Time Label-Free Molecular Sensing

Label-free miniaturized optical sensors can have a tremendous impact on highly sensitive and scalable Point-of-Care (PoC) diagnostics by monitoring in real-time molecular interactions without any labels. However, current biophotonic platforms are limited by complex optical and external readout equipment, precluding their use in a PoC setting. In this research, we aim to address this challenge by developing a first of its kind fully integrated electronic-photonic real-time label-free molecular sensor utilizing micro-ring resonators (MRRs) co-integrated with on-chip electronics in a high volume advanced electronic process. This technology will reduce cost and enable self-contained and miniaturized Point-of-Care devices that are needed in healthcare applications.This thesis introduces an arrayed electronic-photonic system-on-chip (EPSoC) in GlobalFoundries (GF) 45nm RFSOI with 60 5μm radius MRRs connected to on-chip receivers, approaching a limit of detection (LoD) equivalent to a single 140nm viral particle. In order to deliver multiple fluidic solutions and enable multi-analyte sensing, we propose an efficient packaging strategy for fabricating multi-channel microfluidic networks interfacing with mm-scale chips. Leveraging co-integration of planar MRRs with on-chip receivers, we eliminate the need for a tunable laser and external readout equipment by shifting the requirements of resonance tuning and readout processing to the electronic domain. To further enhance the LoD we propose a dual-ring phase-based sensing architecture, boosting the system’s sensitivity by 3.7x compared to intensity-based single MRR schemes. The inherent intrinsic limitations of MRRs due to environmental variations are addressed with an on-chip differential scheme using sensing and reference rings to cancel common mode errors. We demonstrate the sensing capabilities of the EPSoC by monitoring in real-time binding events of proteins and nanoparticles, unlocking the door towards self-contained fully integrated Lab-on-Chip (LoC) photonic sensors for PoC applications

From language to strategic communication: didactic approaches for the optimisation of communication in public administration

The aim of this doctoral thesis is to highlight the issues that arise in relation to the use of Modern Greek terminology in public documents, the transparency and clarity of which are of fundamental importance for an effective communication and in general for the relationship between the State and its officials as well as the State and the citizens, and ultimately for an efficient and fair Public Administration.This research was conducted by taking into consideration the language training provided by public education to citizens in general as well as to public officials in particular, and highlights aspects and manifestations related directly or indirectly, to communication as it develops between the Public Administration and its employees, on the one hand, and the citizens, on the other.In particular, the study analyses Communication as the uninterrupted human activity through which every interaction is carried out in the context of Public Administration with a focus on Strategic Communication and as an interdisciplinary and holistic tool for achieving communication goals. It also records and comments on the way intra-organisational written communication is organised and functions in the social area of the Hellenic Public Administration, as conducted through administrative documents, with a focus on their language, syntax and writing style. In addition, it presents the design, planning and organisation of field research with an emphasis on the analysis and justification of the chosen methodology as a valid scientific tool for extracting reliable, safe and objective conclusions and formulating relevant and suitable proposals for the sociolinguistic issue under research, while recording and commenting on the information derived from the answers of civil servants who voluntarily participated in the field survey. Finally, it attempts a short but thorough review of the historical presence of the phenomenon under research by focusing on the way in which the official Hellenic State has managed the whole situation from the Post-colonial era to the present day and, at the same time, lists and analyses the relevant improvement proposals made by the participants in the field research, i.e. civil servants.Στόχος της παρούσας διδακτορικής διατριβής είναι η ανάδειξη των ζητημάτων που προκύπτουν σε σχέση με τη χρήση νεοελληνικής ορολογίας στα δημόσια έγγραφα, η διαφάνεια και η σαφήνεια των οποίων είναι κεφαλαιώδους σημασίας για την επικοινωνία και γενικότερα για τη σχέση μεταξύ Δημοσίου και Υπαλλήλων του καθώς και Δημοσίου και Πολίτη, αναφορικά με την αποτελεσματική και δίκαιη Δημόσια Διοίκηση. Η έρευνα αυτή διεξήχθη σε σχέση με τη γλωσσική κατάρτιση που παρέχει η δημόσια εκπαίδευση στους πολίτες και τους δημοσίους υπαλλήλους και ειδικότερα αναδεικνύει πτυχές και εκφάνσεις που σχετίζονται, άλλοτε άμεσα και άλλοτε έμμεσα με την επικοινωνία όπως αναπτύσσεται ανάμεσα στη Δημόσια Διοίκηση και τους υπαλλήλους της, αφενός, και ανάμεσα στη Διοίκηση και τους πολίτες, αφετέρου.Ειδικότερα, η μελέτη αναλύει την Επικοινωνία, ως την αδιάλειπτη εκείνη ανθρώπινη δραστηριότητα μέσω της οποίας διενεργείται κάθε διάδραση στο πλαίσιο της Δημόσιας Διοίκησης, με εστίαση στη Στρατηγική Επικοινωνία, ως διεπιστημονικό και ολιστικό εργαλείο επίτευξης επικοινωνιακών εγχειρημάτων. Επίσης, καταγράφει και σχολιάζει τον τρόπο οργάνωσης και λειτουργίας της ενδοοργανωσιακής γραπτής επικοινωνίας στον κοινωνικό «χώρο» της Ελληνικής Δημόσιας Διοίκησης, όπως διεξάγεται μέσω των διοικητικών εγγράφων, με εστίαση στη γλώσσα, τη σύνταξη και το ύφος συγγραφής τους. Επιπλέον, παρουσιάζει το σχεδιασμό, τον προγραμματισμό και την οργάνωση της έρευνας πεδίου με έμφαση στην ανάλυση και την αιτιολόγηση της επιλεγμένης μεθοδολογίας ως έγκυρου επιστημονικού εργαλείου για την εξαγωγή αξιόπιστων, ασφαλών και αντικειμενικών συμπερασμάτων και τη διατύπωση ανάλογων και κατάλληλων προτάσεων βελτιστοποίησης του διερευνώμενου κοινωνιογλωσσικού ζητήματος, ενώ καταγράφει και σχολιάζει τις πληροφορίες που αντλήθηκαν από τις απαντήσεις των δημοσίων υπαλλήλων οι οποίοι συμμετείχαν εθελοντικά στην έρευνα πεδίου. Τέλος, επιχειρεί μια σύντομη αλλά εμπεριστατωμένη αναδρομή στην ιστορική παρουσία του φαινομένου με εστίαση στον τρόπο με τον οποίο το επίσημο Ελληνικό Κράτος έχει διαχειριστεί την κατάσταση αυτή από την εποχή της Μεταπολίτευσης έως τις ημέρες μας και παράλληλα παραθέτει και αναλύει τις σχετικές προτάσεις εξυγίανσης τις οποίες διατύπωσαν οι συμμετέχοντες, δημόσιοι υπάλληλοι, στην έρευνα πεδίου