https://www.um.edu.mt/library/oar/handle/123456789/34081 2026-05-27T12:12:00Z https://www.um.edu.mt/library/oar/handle/123456789/42773 Title: Cognitive neuroscience of cocaine drug use. Abstract: Based on theories, such as the Dopamine Hypothesis, Schultz (1997, 2006), and Hyman's (2005) outlook on addiction as a disease of learning and memory, the main objective of this study was to assess for the first time, whether cognitive performance, with respect to Associative Learning, in a population of Cocaine users, was compromised. Secondary objectives included the identification plus confirmation of additional characteristics that might be related to the development and maintenance of the addiction. This was achieved by employing a quantitative approach, through the use of a battery of cognitive, biopsychosocial and demographic tests. These tests included a computer based Kamin Blocking and Latent Inhibition Test, in addition to a Beck Depression Inventory-Il, and a European Addiction Severity Index. Reported results confirm that in Cocaine-users, cognitive alterations on performance were evident when compared to their age, gender and education matched counterparts. A number of additional characteristics shaping the development and maintenance of the drug addiction in question were also established. Moreover, this work, succeeds in providing reliable data that could eventually facilitate the understanding of why cocaine users are more susceptible to relapse. Keywords: COCAINE ADDICTION, AETIOLOGY, ASSOCIATIVE LEARNING, KAMIN BLOCKING, LATENT INHIBITION, DOPAMINE HYPOTHESIS. Description: M.SC.BIOMED.SCI. 2011-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/34104 Title: Molecular biomarkers associated with mutant BRCAl breast cancer patients Abstract: The presence of mutations in the BRCA1 gene has been linked to a worse overall prognosis in the case of breast cancer. Furthermore, its mutational status has been linked to susceptibility or resistance to certain adjuvant therapies used in the treatment of the cancer. This study aims at investigating the feasibility of using phospho-Akt (Serine-473) status as a biomarker for mutant BRCA1 gene and generation of a cellular model for the measurement of Akt activation with respect to BRCA1 mutational status. The use of p-Akt as a biomarker is supported by other studies which showed that inhibition of BRCA1 activity leads to increased phosphorylation of Akt (Xiang, et aI., 2008). Formalin-fixed paraffin-embedded (FFPE) triple negative breast cancer samples were stained with an antibody raised against phosphorylated Ser-473 in Akt (p-Akt (S473)) and an attempt was made to correlate the intensity of staining with the presence of mutations in the BRCA1 gene. A subset of triple negative breast cancer cases (53%) was found to have high p-Akt. Cases with high Akt activation may derive greater benefit from therapies targeting the Akt/mTor pathway. This is supported by the finding that FTY720 (at l/µM), an activator of PP2A (a phosphatase that inhibits Akt activity) suppresses Akt activation in MCF-7 and HCC1937 cells stimulated by IGF-1 (a stimulator of Akt), indicating that p-Akt (S473) is a potential predictive biomarker. Mutational analysis of triple negative breast cancers has revealed the presence of two novel . mutations: IVS2+38insTA in the second intron of BR CA 1, and 5384G>T in exon 20. Further studies are required to investigate the function of the identified mutations in BRCA1 and their significance in disease. Description: M.SC.BIOMED.SCI. 2011-01-01T00:00:00Z