Biochemical, computer, and spectroscopic techniques applied to the study of prions and of combinations of antineoplastic drugs
type: CreativeWork
description: This thesis collects the work I have done during the three-year PhD Course. The results obtained are divided according to the research topics addressed: · Drug discovery of anticancer agents and development of synergistic associations (Part I); · Studies on the prion structure and the pathogenesis of prion diseases (Part II). Studies referring to the Part I have been carried out at the University of Cagliari and were focalized on the evaluation and experimental validation of the method known as Artificial Neural Network (ANN), which allows to determine, and also to predict, types and degree of interaction of two or more drugs in combination with one another(s). I have successfully applied the ANN approach to combinations of two cytotoxic compounds, i.e. cis-platinum (CDDP), a potent antineoplastic used in the therapy of some types of carcinoma, with Cu(II) complexes that were previously shown to be endowed with potent cytotoxic activity in vitro (Pivetta et al., J Inorg Biochem. 2011 and 2012). Binary combinations comprising CDDP and Cu(II) complexes revealed (Part I, Chapter I) a strong synergistic cytotoxic effect against leukemia cell lines (Pivetta et al., Talanta 2013). The synergistic effect was confirmed in CDDP-resistant leukemia and ovarian cancer cell lines (Part I, Chapter II). Investigations on molecular bases of the CDDP – Cu(II) complexes synergism are in progress. As for the Part II of my research, I firstly investigated the mechanisms underlying the process of generation of pathogenic prion protein (PrPSc). These studies were carried out in part at the University of Cagliari, and in part at the Rocky Mountains Laboratories (RML) of the NIAID/NIH in USA (Hamilton, Montana), during my 14-month research internship as supplemental visiting fellow in a graduate partnership program. The studies carried out in Cagliari have investigated 1H NMR modifications of brain metabolite profiles in sheep from a Sardinian farm hit by natural Scrapie with the aim to di…
abstract: This thesis collects the work I have done during the three-year PhD Course. The results obtained are divided according to the research topics addressed: · Drug discovery of anticancer agents and development of synergistic associations (Part I); · Studies on the prion structure and the pathogenesis of prion diseases (Part II). Studies referring to the Part I have been carried out at the University of Cagliari and were focalized on the evaluation and experimental validation of the method known as Artificial Neural Network (ANN), which allows to determine, and also to predict, types and degree of interaction of two or more drugs in combination with one another(s). I have successfully applied the ANN approach to combinations of two cytotoxic compounds, i.e. cis-platinum (CDDP), a potent antineoplastic used in the therapy of some types of carcinoma, with Cu(II) complexes that were previously shown to be endowed with potent cytotoxic activity in vitro (Pivetta et al., J Inorg Biochem. 2011 and 2012). Binary combinations comprising CDDP and Cu(II) complexes revealed (Part I, Chapter I) a strong synergistic cytotoxic effect against leukemia cell lines (Pivetta et al., Talanta 2013). The synergistic effect was confirmed in CDDP-resistant leukemia and ovarian cancer cell lines (Part I, Chapter II). Investigations on molecular bases of the CDDP – Cu(II) complexes synergism are in progress. As for the Part II of my research, I firstly investigated the mechanisms underlying the process of generation of pathogenic prion protein (PrPSc). These studies were carried out in part at the University of Cagliari, and in part at the Rocky Mountains Laboratories (RML) of the NIAID/NIH in USA (Hamilton, Montana), during my 14-month research internship as supplemental visiting fellow in a graduate partnership program. The studies carried out in Cagliari have investigated 1H NMR modifications of brain metabolite profiles in sheep from a Sardinian farm hit by natural Scrapie with the aim to di…
author: PERRA, DANIELA
language: eng
keywords: Artificial Neural Network, PrPSc, anticancer agents, prion structure, Settore BIO/19 - Microbiologia Generale
date published: 2015-05-22
date modified: 2026-07-24T01:30:07Z
provider: Università di Cagliari
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Cagliari

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property ID: Handle
value: http://hdl.handle.net/11584/266787