Τομέας Βιοχημείας Μοριακής Βιολογίας
Library of the School of Science

2016-02-19

2016

Αυγέρης Μαργαρίτης

Τριμελής Συμβουλευτική Επιτροπή: Σκορίλας Ανδρέας, Καθηγητής, Τμήμα Βιολογίας, Ε.Κ.Π.Α. (Επιβλέπων), Φραγκούλης Γ. Εμμανουήλ, Ομότιμος Καθηγητής, Τμήμα Βιολογίας, Ε.Κ.Π.Α., Κλέτσας Δημήτριος, Διευθυντής Ερευνών, Ινστιτούτο Βιολογίας, ΕΚΕΦΕ «Δημόκριτος»

Μελέτη ρύθμισης της γονιδιακής έκφρασης, μέσω μορίων microRNA, της L-DOPA αποκαρβοξυλάσης και των καλλικρεϊνών στον καρκίνο του προστάτη και της ουροδόχου κύστεως: Αξιολόγηση της διαφοροδιαγνωστικής και προγνωστικής τους αξίας

Greek

Study of L-DOPA decarboxylase and kallikreins gene expression regulation through microRNA molecules, in prostate and bladder cancers: Evaluation of their differential diagnostic and prognostic value

One of the main features of prostate and bladder cancers is their clinical
heterogeneity, in terms of disease progression rate, patients’ survival and
treatment response. Therefore, the studying of the different molecular
signatures of the disease and the identification of novel molecular biomarkers
could offer, an alternative approach to improve disease prognosis and to
support personalized treatment decisions, and is of first research and clinical
priority.
L-DOPA decarboxylase (DDC) was recently identified as a novel co-activator of
androgen receptor (AR), enhancing the ligand-dependent AR transcriptional
activity. Additionally, DDC represents also a marker of the neuroendocrine (NE)
differentiation of the prostate. The NE prostate cells play essential role in
prostate cancer progression. Tissue kallikrein (KLK1) and the
kallikrein-related peptidases (KLK2-KLK15) constitute a family of 15 homologous
secreted serine proteases. The value of KLKs as cancer biomarkers is
highlighted by the previously established clinical utility of prostate specific
antigen (PSA), as kallikrein-related peptidase 3 (KLK3) is largely known, for
prostate cancer diagnosis and treatment monitoring. Finally, microRNAs (miRNAs)
are a rapidly growing family of small (~22nt) non-coding RNAs, representing the
most powerful gene expression regulators at the post-transcriptional level.
Their function is crucial for cellular homeostasis, and the deregulation of
miRNAs expression has become a hallmark of the majority of human malignancies.
In the present Ph.D. Thesis is performed the expression analysis and the
evaluation of the clinical significance of DDC, KLKs genes, and miRNAs
molecules, which regulate their expression post-transcriptionally, in prostate
and bladder cancers. To fulfill these objectives, a statistically significant
number of 137 prostate and 279 blabber fresh frozen tissues were collected,
processed and included in the study. Moreover, novel molecular methodologies
were developed and optimized for the accurate and sensitive quantification of
the tested genes and miRNAs in prostate and bladder tissue specimens.
Additionally, a detailed database of patients’ history, clincopathological and
follow-up data has been constructed for all patients. The analysis of the total
number of tissue specimens and the extended statistical analysis of the results
of the study highlighted the significant clinical value of the tested
biomarkers for the differential diagnosis and the accurate prognosis of
prostate and bladder cancers.

Prostate cancer, Bladder cancer, miRNA, L-DOPA decarboxylase, Kallikrein-related peptidases

Yes

vii - xiv

Yes

742

425

File access is restricted.

https://pergamos.lib.uoa.gr/uoa/dl/object/1309067