Προγραμματισμένος κυτταρικός θάνατος.Η εμπλοκή του σε παθήσεις και νόσους του βλεννογόνου του στόματος
Creators: name: Λέτσα, Σπυριδούλα Φωτίου
Publisher: name: Aristotle University of Thessaloniki
Year: 2017
Subjects: απόπτωση
καρκίνος στόματος
ομαλός λειχήνας
apoptosis
oral cancer
oral diseases

description: Στην παρούσα βιβλιογραφική ανασκόπηση συλλέξαμε τα πιο πρόσφατα στοιχεία που αφορούν στην απόπτωση, τα μόρια αυτής σε σχέση με τις διάφορες νοσολογικές οντότητες που ανήκουν στο πλαίσιο της Στοματολογίας. Αρχικά παρουσιάζονται τα μοριακά μονοπάτια και οι πρωτεΐνες της απόπτωσης, με ακόλουθη παρουσίαση μονοπατιών ανεξάρτητων από τις βασικές πρωτεΐνες της απόπτωσης, τις κασπάσες, καθώς και κάποιοι αναστολείς της αποπτωτικής διαδικασίας. Στη συνέχεια γίνεται αναφορά της σημασίας και των μηχανισμών της απόπτωσης σε άλλους οργανισμούς εκτός του ανθρώπου και έπειτα παρουσιάζονται στοιχεία νευροεκφυλιστικών, ρευματολογικών και άλλων νόσων που συνδέουν την παθογένεια αυτών με την απόπτωση. Το τελευταίο μέρος αφορά συνοπτική αναφορά των δεδομένων σε μερικές από τις κύριες και συχνές παθήσεις και κακοήθειες του στόματος με ξεχωριστή παρουσίαση του καρκίνου του στόματος. Στο τέλος παρουσιάζονται τα συμπεράσματα και τα σημαντικότερα στοιχεία της συγκεκριμένης ανασκόπησης
description: The aim of the current thesis was the review of apoptosis in oral cancer and common oral diseases. Cell death appears to be a basic phenomenon which is maintained by the human body. Apoptosis is essential for development, growth and tissue homeostasis. Alteration in its molecular mechanisms contributes to a range of diseases in general and in oral cavity. After many researches it is become known apoptosis and its mechanisms to be crucial therapeutic targets. The review summarizes the mechanisms of apoptosis, its relation to neurodegenerative disorders and autoimmune diseases and focus on the latest facts considering apoptosis and oral diseases. Methods: A systematic literature search of the electronic database PubMed and google scholar from 2006-2016 was performed. A combination of the following terms was used for the search: ‘apoptosis, Bcl-2,Bax, Fas, p53,m TOR, caspases, granzymes, drosophila melanogaster, C.elegans, plants, S.cerevicae, immune system, autoimmune diseases, systemic erythematosus lupus, rheumatoid arthritis, Alzheimer disease, cancer, malignant transformation, lichen planus, pemphigus, pemphigoid, Sjögren syndrome, oral cancer, melanoma, oral papilloma, oral fibrosis, adenoid cystic carcinoma, mucoepidermoid carcima, pleomorphic adenoma, carcinoma ex pleomorphic adenoma, apthous ulceration, Stevens-Johnson disease, oral candidiasis, oral leukoplakia, Behcet disease’.Irrelevant and repeated studies were indentified and excluded. The remaining literature was reviewed for additional pertinent studies. Finally, all the associated publications were included and studied in order to summarize the key facts for its disease.A total number of 35 reports of lichen planus and malignant transformation were able to accessed and were relevant. A total number of 6 articles of Bcl-2 and lichen planus were obtained were able to accessed and were relevant. For Bax and oral lichen planus were 3. For p53 and oral lichen planus only 14 were relevant and we were able to access. For apoptosis and lichen planus only 22 were included. For Fas/FasL and lichen planus the number decreased to 3 articles that were used. For caspases and lichen planus 4 reports were included. For granzymes and oral lichen planus the 5 articles that were found were not included. For apoptosis and oral cancer a total number of 41 were included. For Bcl-2 and oral cancer 7 articles were used. For p53 and oral cancer 26 were included. For Bax and oral cancer 4 reports were used. For apoptosis and bullus pemphigoid 2 articles were found and used. For apoptosis and pemphigus 10 articles were included. For Fas 2 articles were found and used. For caspase-3 1 article was found and used. For apoptosis and Sjögren syndrome a total number of 13 articles were found and included. Bcl-2 and Sjögren syndrome gave 1 article that was inadequate to use. For Bax and Sjögren syndrome 2 were found and only one was included. For Fas and Sjögren syndrome 3 were used. For apoptosis and melanoma 10 were included, Fas and melanoma gave 1 inadequate article and p53 and melanoma gave 2 articles which we used. For apoptosis and adenoid cystic carcinoma 11 articles were found and used. Bcl-2 and p53 and adenoid cystic carcinoma 3 articles were found and included. For apoptosis and mucoepidermoid carcinoma 8 articles were found and used, Bcl-2 and mucoepidermoid carcinoma 3 reports were found and used, and 1 for p53. For pleomorphic adenoma and apoptosis, Bcl-2 and p53 3, 2 and 1 article were found and used respectively. For carcinoma ex pleomorphic adenoma only 3 articles were found with report for p53 and XIAP. For apoptosis and oral leukoplakia 3 reports were found and included and 1 for p53. For Stevens-Johnson disease 3 articles were found for apoptosis and Fas. For apoptosis and oral candidiasis 7 articles were found and used. For apoptosis, Bcl-2, Bax and apthous ulceration 2 articles were found and used respectively. And for apoptosis and Behcet disease 3/4 were included. After review of the above articles significant conclusions for its disease were made.Conclusions: Considering the oral cancer was made clear that p53 is a essential prognostic factor and the expression of p53 higher than 50% is associated with low outcome. Through numerous researches proteins such as MDM2, cdh1(E-cadherin), EGFR and cyclin D1 in combination with the expression of p53 were considered significant prognostic factors. In the other hand, many natural products were able to induce apoptosis through activation of caspase-3,-9 or via p38MAPK pathways through the activation by ROS. Some other potential drugs induced apoptosis through permeabilization of mitochondrial membrane and release of Cyt c and activation of the intrinsic apoptotic pathway. Considering oral lichen planus was became clear that apoptosis is involved in its pathogenesis. T-cytotoxic lymphocytes release cytokines that induce apoptosis in the oral epithelial cells. Also,apoptosis proved to be linked with acantholysis and the formation of vesicles in pemphigus and pemphigoid. Apoptosis and its molecules, Bcl-2 were found to be essential in the pathogenesis of mucoepidermoid and adenoid cystic carcinoma. Furthermore, autophagic protein Beclin-1 was associated in reverse with apoptosis and was significant for the progression of adenoid cystic carcinoma. From several reports is noted that the oral melanoma is not associated with the exposure to natural light and the potential therapies are able to induce apoptosis with activation of Akt/m TOR pathway and the intrinsic pathway. Many researchers used natural products and drugs in cell lines in order to prove possible potential use of them through the induction of apoptosis. In Sjögren syndrome apoptosis was able to be induced by the autoantibodies anti-Ro and anti-La and in other reports the negative regulation of Fas and its gene mutation lead to increase proliferation of lymphocytes and lymphocytic infiltration. In oral leukoplakia negative regulation or knockdown of Bcl-2 seems to play a crucial role to its pathogenesis. In Stevens-Johnson disease soluble Fas was found to be increased in the early stages of the disease, so it may be a potential prognostic factor of its progression. The pathogenesis of apthous ulceration is associated with abnormal apoptosis that leads to a secondary necrosis and it seems that apoptotic products and molecules increase the secretion of inflammation cytokines. In the end, Candida albicans induce apoptosis after entering the epithelial cells with the input of Ca+2 in the cells to be an early event of apoptosis by candida. Through studying of several reports, reviews and researches apoptosis and its mechanisms seem to contribute to pathogenesis of many diseases and it is essential for the future studies to focus in chemotherapeutic agents that increase and regulate apoptosis