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Identifier uch.med.phd//2001dokianaki
Title Προσδιορισμός μεταλλάξεων στα γονίδια RAS, γενετικών αλλοιώσεων στο γονίδιο της P53 και των ιών του θηλώματος του ανθρώπου (HPY) σε κυτταρολογικό υλικό από γυναικολογικούς καρκίνους και προκαρκινικές αλλοιώσεις
Creator Dokianaki, Despina N
Abstract The multi-event nature of carcinogenesis has led to extensive studies focusing on the involvement of several cellular oncogenes, oncosuppressor genes, viral genes and their combined participation in the development of human cancers. The collaboration of a variety of genetic factors, gene mutations and specific gene polymorphism in female genital cancer lesions and their interactions and correlation with their host and the environment have also been extensively studied. In the present study, the pattern of point mutations at codon 12 of the K-ras, H-ras and N-ras genes was investigated, using the polymerase chain reaction and restriction fragment length polymorphism analysis, in human cytological specimens from female genital malignant and premalignant lesions.In parallel, the pattern of point mutations at codon 12 of the K-ras, H-ras and N-ras genes was studied in malignant cytological specimens of ovarian adenocarcinoma peritoneal and ascitic fluids. The purpose of this study was also to detect and identify the human papillomaviruses in stained cervical smears and to correlate them with the other parameters studied and with the clinicopathological parameters of the patients. Regarding the association between p53 polymorphisms and risk for HPV-associated cervical cancer. It has been reported that patients with the arginine form have a higher risk of developing cervical cancer than those with the proline form. In the lesions examined, K-ras gene activation by codon 12 point mutations, was the most frequent alteration observed, mutations of H-ras and N-ras were also found although at lower rates. The highest incidence of K-ras mutations was found in ovarian cancer, followed by in cervical cancer (47% and 30% respectively). Activation occurs in early as well as in late stages. It is suggested that activated ras genes could serve as genetic indicators for progression of a lesion to a higher grade, or even as indicators for metastasis. HPV viruses were found to be strongly implicated in the development of cervical lesions, the high risk HPV types were overrepresented. Based on the findings of this study, it is suggested that p53 Arg homozygosity at codon 72 could represent a potential risk factor for the tumorigenesis of high risk HPV-associated cervical cancer. In conclusion, ras activation combined with HPV infection particularly by a high risk type of the virus may be an important step in the development of a substantial numbers of cervical carcinomas, while their interactions with other genes or events may also be involved.
Issue date 2001-05-01
Date available 2001-09-10
Collection   School/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
Permanent Link https://elocus.lib.uoc.gr//dlib/f/d/2/metadata-dlib-2001dokianaki.tkl Bookmark and Share
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