Browsing by Author "Sarmento-Ribeiro, AB"
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- Aberrant p15, p16, p53, and DAPK Gene Methylation in Myelomagenesis: Clinical and Prognostic ImplicationsPublication . Geraldes, C; Gonçalves, AC; Cortesão, E; Pereira, MI; Roque, A; Paiva, A; Ribeiro, L; Nascimento-Costa, JM; Sarmento-Ribeiro, ABBACKGROUND: Aberrant DNA methylation is considered a crucial mechanism in the pathogenesis of monoclonal gammopathies. We aimed to investigate the contribution of hypermethylation of 4 tumor suppressor genes to the multistep process of myelomagenesis. METHODS: The methylation status of p15, p16, p53, and DAPK genes was evaluated in bone marrow samples from 94 patients at diagnosis: monoclonal gammopathy of uncertain significance (MGUS) (n = 48), smoldering multiple myeloma (SMM) (n = 8) and symptomatic multiple myeloma (MM) (n = 38), and from 8 healthy controls by methylation-specific polymerase chain reaction analysis. RESULTS: Overall, 63% of patients with MM and 39% of patients with MGUS presented at least 1 hypermethylated gene (P < .05). No aberrant methylation was detected in normal bone marrow. The frequency of methylation for individual genes in patients with MGUS, SMM, and MM was p15, 15%, 50%, 21%; p16, 15%, 13%, 32%; p53, 2%, 12,5%, 5%, and DAPK, 19%, 25%, 39%, respectively (P < .05). No correlation was found between aberrant methylation and immunophenotypic markers, cytogenetic features, progression-free survival, and overall survival in patients with MM. CONCLUSIONS: The current study supports a relevant role for p15, p16, and DAPK hypermethylation in the genesis of the plasma cell neoplasm. DAPK hypermethylation also might be an important step in the progression from MGUS to MM.
- Impact of splenic artery ligation after major hepatectomy on liver function, regeneration and viabilityPublication . Carrapita, J; Abrantes, AM; Campelos, S; Gonçalves, AC; Cardoso, D; Sarmento-Ribeiro, AB; Rocha, C; Santos, JN; Botelho, MF; Tralhão, JG; Farges, O; Barbosa, JMIt was reported that prevention of acute portal overpressure in small-for-size livers by inflow modulation results in a better postoperative outcome. The aim is to investigate the impact of portal blood flow reduction by splenic artery ligation after major hepatectomy in a murine model. Forty-eight rats were subjected to an 85% hepatectomy or 85% hepatectomy and splenic artery ligation. Both groups were evaluated at 24, 48, 72 and 120 post-operative hours: liver function, regeneration and viability. All methods and experiments were carried out in accordance with Coimbra University guidelines. Splenic artery ligation produces viability increase after 24 h, induces a relative decrease in oxidative stress during the first 48 hours, allows antioxidant capacity increment after 24 h, which is reflected in a decrease of half-time normalized liver curve at 48 h and at 72 h and in an increase of mitotic index between 48 h and 72 h. Splenic artery ligation combined with 85% hepatectomy in a murine model, allows portal inflow modulation, promoting an increase in hepatocellular viability and regeneration, without impairing the function, probably by inducing a less marked elevation of oxidative stress at first 48 hours.
- Influence of P53 on the radiotherapy response of hepatocellular carcinomaPublication . Gomes, AR; Abrantes, AM; Brito, AF; Laranjo, M; Casalta-Lopes, JE; Gonçalves, AC; Sarmento-Ribeiro, AB; Botelho, MF; Tralhão, JGHepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it has a poor prognosis and few therapeutic options. Radiotherapy is one of the most effective forms of cancer treatment, and P53 protein is one of the key molecules determining how a cell responds to radiotherapy. The aim of this study was to determine the therapeutic efficacy of iodine-131 in three human HCC cell lines.
- Study of hepatocellular function in the murine model following hepatic artery selective clampingPublication . Tralhão, JG; Abrantes, AM; Gonçalves, AC; Hoti, E; Laranjo, M; Martins, R; Oliveiros, B; Cardoso, D; Sarmento-Ribeiro, AB; Botelho, MF; Castro e Sousa, FPURPOSE: To investigate the impact of selective hepatic artery clamping (SHAC) in hepatocellular function. METHODS: Three groups of Wistar male rats were subjected to SHAC ischemia period of 60min: Group A continuous SHAC were subjected to SHAC ischemia period of 60min, Group B intermittent SHAC of 30min with 5min of reperfusion and Group C intermittent SHAC of 15min with 5min of reperfusion. Animals without SHAC were included-Group D. To evaluate hepatocellular function blood markers and hepatic extraction function (HEF) using 99mTc-mebrofenin were performed before and after surgery. Flow cytometry was used to analyze oxidative stress and cell viability. RESULTS: A mortality rate of 7.6% in Group A was observed. HEF maintained normal values between the groups. Flow cytometry demonstrated no significant differences between the groups in viability, type of cell death as well as in the production of reactive oxygen species. CONCLUSIONS: The selective hepatic artery clamping compared to other clamping techniques results on increased cell viability and decreased hepatocyte death. The SHAC is a potential alternative to decrease per-operative bleeding while maintaining hepatocellular function.