E-Locus - Institutional Repository of the University of Crete

Home Search

Results - Details

Search command : Author="Ζερβού" And Author="Μαρία"

Current Record: 1 of 14

[Add to Basket]

Identifier

000455944

Title

Μελέτη των μηχανισμών αλληλεπίδρασης της κυτταρικής απόκρισης και του μεταβολώματος έπειτα από χορήγηση νέων συνθετικών μορίων ανάλογων πουρίνης σε μοντέλα καρκίνου μαστού in vitro και in vivo

Alternative Title

Study of the interacion mechanisms of cellular response and metabolome after administration of novel synthetic purine analoques in breast cancer models in vitro and in vivo

Author

Μάλαμος, Παναγιώτης

Thesis advisor

Ζερβού, Μαρία

Reviewer

Στέλλας Δημήτριος
Σουλιώτης, Βασίλειος

Abstract

Over the years, purine metabolism has been a target for the discovery of novel antineoplastic drugs, since it has been found to be disrupted in many malignancies. Purine antimetabolites interfere with the DNA during S-phase and block important physiological processes like cell replication and development. A group of newly synthesized 1,4,6-tris-substituted pyrazolo[3,4-b]pyridines had shown promising results by inhibiting cell proliferation in breast (EO771) and pancreatic (KPC) murine cell lines. The analogue MG71 ((4-methylpiperazin-1-yl)ethoxy) had shown in vivo, to inhibit tumor growth and cell proliferation and also to promote apoptosis in murine breast cancer models. For this master thesis, NMR-metabolomic studies and multivariate statistical analysis were performed on tissues (breast tumors, kidneys), in order to identify metabolic changes due to MG71 injections in vivo. Pathway analysis on altered metabolites of the tumors shows important changes in purine biosynthesis and many of its interacting pathways suggesting possible inhibition by the analogue. On the other, metabolomic analysis on kidneys revealed no statistical changes between animals injected with MG71 and the control group. This may be due to absence of kidneys drug toxicity. Alongside, a group of 26 new MG71 analogues were synthesized and their effect on cell proliferation was calculated with SRB assay in vitro (breast murine cell line, EO771). Only one of those was found to be selective for cancer cells compared with normal cells.

Language

Greek, English

Subject

Antimetabolites

Cell toxicity

Nuclear magnetic resonance

Ανάλογα Πουρίνης

Αντιμεταβολίτες

Κυτταροτοξικότητα

Μεταβολομική

Πυρηνικός μαγνητικός συντονισμός

Issue date