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Η πλειονότητα των προσβολών του κολποτραχηλικού επιθηλίου από τον ιο του ανθρώπινου θηλώματος (Human Papilloma Virus-HPV) χαρακτηρίζονται ασυμπτωματικές με τάση υποστροφής, ενώ η δημιουργία εμφανών κυτταρομορφολογικών αλλοιώσεων (κοιλοκύτταρα) στο τεστ ΠΑΠ εκτείνεται σε ένα διάστημα από 3 εβδομάδες εώς 9 μήνες μετά την ενσφήνωση του ιού στο κολποτραχηλικό επιθήλιο. Η ενσωμάτωση –σε αντίθεση με την απλή επισωματική προσβολή- των υψηλής επικινδυνότητας υπότυπων του ιού HPV στο DNA των κυττάρων του ξενιστή τροποποιεί τα επιθηλιακά κύτταρα με την απενεργοποίηση των ογκοκατασταλτικών πρωτεϊνών p53 και Rb (5,9,22). Κατά την HPV προσβολή του τραχηλικού συστήματος, η υπερέκφραση της πρωτείνης p16 πραγματοποιείται μέσω της ενεργοποίησης του Ε7 γονιδίου που οδηγεί σε αποσυγχρονισμό του Rb και του Ε2F μεταγραφικού παράγοντα. (11) Ο αποσυγχρονισμός του κυτταρικού κύκλου κατά την εμμένουσα High Risk HPV προσβολή του κολποτραχηλικού επιθηλίου εμπλέκει εκτός των προαναφερθέντων και τα μόρια cyclinD1 και MDM2, καθώς παρατηρείται διαταραχή στην έκφραση τους στα εν λόγω επιθήλια και αποτελεί νέο πεδίο έρευνας ειδικά για τα δίπολα p16/cyclinD1 και p53/MDM2. (23,26,56,58,59,82,85,103) Το εν λόγω ερευνητικό πρωτόκολλο σχεδιάστηκε με γνώμονα τη διερεύνηση του ρόλου της απορρύθμισης των πρωτεινών p16/cyclinD1/p53/MDM2 στο κολποτραχηλικό επιθήλιο κατά την προσβολή του από τον ιο των ανθρωπίνων θηλωμάτων (HPV) με βάση τα επίπεδα της έκφρασής τους σε παθολογικά κολποτραχηλικά επιχρίσματα. Όλοι οι εξεταζόμενοι πρωτεινικοί δείκτες εμφάνισαν διαφορετική έκφραση επί των εξεταζόμενων ανοσοχρωσμένων πλακιδίων (υπερέκφραση ως υψηλή και μέτρια ένταση χρώσης καθώς και χαμηλή). Υπερέκφραση της p53 παρατηρήθηκε σε 13/80 (16.25%), της MDM2 σε 27/80 (33.75%) της cyclin D1 σε 8/80 (10%) και της p16INK4 σε 9/80 (11.25%). Human papillomavirus (HPV) involvement in cervical carcinogenesis represents a classical template of analyzing viral-mediated carcinogenesis. High Risk (HR) HPV subtypes cause initially a simple (episomal) penetration in target host cells. Persistent HR-HPV infection leads to an HPV-DNA integration into the host cell genome resulting to an aberrant oncogene E6/E7 expression. MDM2, a proto-oncogene encoding for a nuclear-localized E3 ubiquitin ligase, acts as a major negative regulator in p53-MDM2 auto-regulatory pathway. MDM2 directly binds to p53 and represses its transcriptional activity and promotes p53 proteasomal degradation. Our aim was to investigate the role of abnormal p53/MDM2 protein co-expression in HPV-mediated cervical squamous intraepithelial lesions (SIL) and also the role of abnormal Cyclin D1 in them combined with p16INK4A expression. Eighty (n=80) cases characterized as SILs and also borderline ones with molecularly proven HPV infection were examined. Using liquid-based cytology, we constructed ten (n=10) slides each containing eight (n=8) cell spots. Immunocytochemistry (ICC) was performed using anti-Cyclin D1/MDM2/p16/p53 antibodies. Digital image analysis was also implemented for evaluating objectively the protein expression levels on the corresponding stained slides. Cyclin D1 protein over expression was observed in 8/80 (10%) cell spots, whereas low expression rates were detected in 72/80 (90%) cases. Cyclin D1 expression was strongly associated with the HPV type group (HR-HPV) (p=0.001) and borderline with the Cervical Intraepithelial Neoplasia (CIN) categorization (p=0.06). Concerning the influence of marker’s protein expression in SIL categorization, no statistical significance was identified (p=0.10). Cyclin D1 overexpression is observed in a sub set of SILs developed by HR-HPV persistent infection. Although SIL and CIN categorization seem to be not influenced by Cyclin D1 expression levels, mechanisms of gene’s deregulation should be a promising molecular target for discriminating specific genetic signatures in the corresponding initial cervical neoplastic lesions. P53 and especially MDM2 over expression is observed in a sub set of SILs developed by HR-HPV persistent infection in cervical epithelial host cells. SIL and CIN categorization seem to be strongly influenced by p53 expression levels, but not by MDM2 aberrant expression. p16 overexpression also represents a significant and useful biomarker for evaluating progression of SILs/CINs.

This article investigates the contemporary economic role of Crete through its history of many centuries. More specifically, it considers the effect of the natural, climatic and marine environment in the productive economic activity, in the international trade and its relations with its neighbors, as well as Crete’s modern financial, developmental characteristics and its position in the Mediterranean, in Europe and the World. From the review of the relative, with the economy of Crete, bibliography, ranging from antiquity until today, as well as from the analysis of modern related quantitative data, it is realized that the basic elements that determine the economic identity and the position of Crete in the international environment during its extensive history are the ground and the products that it produces, the marine environment and the interconnections that it creates with the world, the climate, and the favorable conditions that it shapes for the flora and the fauna and its human resource, as this develops in the particular historical environment each time. These are the characteristics, along with the multiform and rich accumulated cultural reserve, which Crete can evolve and strengthen in the contemporary world so that it cures its disadvantages and most importantly so that it takes advantage of the developmental surplus of possibilities that it allocates. Crete has all the prerequisite conditions- productive and human resources, research and technological infrastructure, democratically programmed institutions- and allocates the initial conditions for a developmental take off, in the frame of flexible specialization, intelligent and viable growth.

Background: The rising incidence of breast cancer suggests lifestyle and environmental causes. During the last decade many chemicals, among which parabens and aluminium, have been shown to express estrogenic properties in in-vitro and animal studies. A causative relationship theory between chemicals and breast cancer has been proposed. Another theory has linked the use of underarm cosmetics with the increased prevalence of breast cancer in the upper outer quadrant.Purpose: We conducted this study to investigate the presence and distribution of five commonly used esters of para-hydroxybenzoic acid and aluminium, in the female breast and their possible relationship with breast cancer development. We attempted to shed light into the link hypothesis between underarm cosmetics and breast cancer. Materials and methods: Fourty breast cancer patiens who would undergo mastectomy, completed the study questionnaire with information about underarm cosmetics use and other lifestyle and epidemiological parameters. Histological information was retreived from their medical records. We obtained tissue samples from four different regions across every mastectomy specimen, from the axilla to the sternum and analysed them for parabens and aluminium.Results: Parabens and aluminium were found intact in almost all samples. The distribution in the four regions across the breast from the axilla to the sternum was homogenous and independent of the patient’s age, tumor location and hormone receptor status. There were no significant differences in the concentrations between women who had used underarm cosmetics and those who had not, or those who had used them in the past but have now stopped using them. There was no correlation between the length of underarm cosmetic use and the the concentration of parabens and aluminium across the breast.Discussion: This is the first study to demonstrate the presence of five commonly used p-hydroxybenzoic acid esters and aluminium in the healthy female breast tissue. The measured concentrations are low and the pattern of distribution is homogenous but universal in the studied population, thus allowing the expression of their weak estrogenic properties for a lifelong period. We did not find a causative relationship with breast cancer. However, our findings can be added to those from other in-vitro, animal and human studies on the presence, properties, and combined effect of several widely used chemicals with hormonal properties. In the light of this relatively recent evidence there is an urge for developing biomonitoring techniques, determining the total chemical burden, and investigating the mixture effects in humans. Prevention policies should support the reduction of exposure to artificial chemicals, especially to those categorised as endocrine disrupters and for vulnerable groups.Conclusions: Parabens and aluminium can be found intact in the healthy female breast. Underarm deodorants or antiperspirants do not constitute the main source of parabens and aluminium for the female breast and cannot be considered an independent risk factor for breast cancer. Further research is needed to identify the contribution of these chemicals to the total body burden and the possible effect of mixtures in the pathogenesis of breast cancer.