http://comum.rcaap.pt/handle/123456789/1954 2013-05-23T01:16:16Z 2013-05-23T01:16:16Z Costa, BM Viana-Pereira, M Fernandes, R Costa, S Linhares, P Vaz, R Pinheiro, C Lima, J Soares, P Silva, A Pardal, F Amorim, J Nabiço, R Almeida, R Alegria, C Pires, MM Pinheiro, C Carvalho, E Oliveira, P Lopes, JM Reis, RM http://comum.rcaap.pt/handle/123456789/3590 2013-01-10T15:49:46Z 2011-01-01T00:00:00Z

Title: Impact of EGFR genetic variants on glioma risk and patient outcome Authors: Costa, BM; Viana-Pereira, M; Fernandes, R; Costa, S; Linhares, P; Vaz, R; Pinheiro, C; Lima, J; Soares, P; Silva, A; Pardal, F; Amorim, J; Nabiço, R; Almeida, R; Alegria, C; Pires, MM; Pinheiro, C; Carvalho, E; Oliveira, P; Lopes, JM; Reis, RM Abstract: BACKGROUND: The epidermal growth factor receptor (EGFR) regulates important cellular processes and is frequently implicated in human tumors. Three EGFR polymorphisms have been described as having a transcriptional regulatory function: two single-nucleotide polymorphisms in the essential promoter region, -216G/T and -191C/A, and a polymorphic (CA)(n) microsatellite sequence in intron 1. We aimed to elucidate the roles of these EGFR polymorphisms in glioma susceptibility and prognosis. METHODS: We conducted a case-control study with 196 patients with glioma and 168 cancer-free controls. Unconditional multivariate logistic regression models were used to calculate ORs and 95% confidence intervals. A Cox regression model was used to evaluate associations with patient survival. False-positive report probabilities were also assessed. RESULTS: None of the EGFR -216G/T variants was significantly associated with glioma risk. The -191C/A genotype was associated with higher risk for glioma when the (CA)(n) alleles were classified as short for ≤16 or ≤17 repeats. Independently of the (CA)(n) repeat cutoff point used, shorter (CA)(n) repeat variants were significantly associated with increased risk for glioma, particularly glioblastoma and oligodendroglioma. In all tested models with different (CA)(n) cutoff points, only -191C/A genotype was consistently associated with improved survival of patients with glioblastoma. CONCLUSIONS: Our findings implicate EGFR -191C/A and the (CA)(n) repeat polymorphisms as risk factors for gliomas, and suggest -191C/A as a prognostic marker in glioblastoma. IMPACT: Our data support a role of these EGFR polymorphisms in determining glioma susceptibility, with potential relevance for molecularly based stratification of patients with glioblastoma for individualized therapies

2011-01-01T00:00:00Z Marques, H Catarino, R Domingues, N Barros, E Portela, C Almeida, MI Costa, S Reis, RM Medeiros, R Longatto-Filho, A http://comum.rcaap.pt/handle/123456789/3496 2012-12-18T02:14:36Z 2012-01-01T00:00:00Z

Title: Detection of the Epstein-Barr virus in blood and bone marrow mononuclear cells of patients with aggressive B-cell non-Hodgkin's lymphoma is not associated with prognosis Authors: Marques, H; Catarino, R; Domingues, N; Barros, E; Portela, C; Almeida, MI; Costa, S; Reis, RM; Medeiros, R; Longatto-Filho, A Abstract: The Epstein-Barr virus (EBV) is associated with a large spectrum of lymphoproliferative diseases. Traditional methods of EBV detection include the immunohistochemical identification of viral proteins and DNA probes to the viral genome in tumoral tissue. The present study explored the detection of the EBV genome, using the BALF5 gene, in the bone marrow or blood mononuclear cells of patients with diffuse large B-cell lymphomas (DLBCL) and related its presence to the clinical variables and risk factors. The results show that EBV detection in 21.5% of patients is not associated with age, gender, staging, B symptoms, international prognostic index scores or any analytical parameters, including lactate dehydrogenase (LDH) or β-2 microglobulin (B2M). The majority of patients were treated with R-CHOP-like (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone or an equivalent combination) and some with CHOP-like chemotherapy. Response rates [complete response (CR) + partial response (PR)] were not significantly different between EBV-negative and -positive cases, with 93.2 and 88.9%, respectively. The survival rate was also similar in the two groups, with 5-year overall survival (OS) rates of 64.3 and 76.7%, respectively. However, when analyzing the treatment groups separately there was a trend in EBV-positive patients for a worse prognosis in patients treated with CHOP-like regimens that was not identified in patients treated with R-CHOP-like regimens. We conclude that EBV detection in the bone marrow and blood mononuclear cells of DLBC patients has the same frequency of EBV detection on tumoral lymphoma tissue but is not associated with the risk factors, response rate and survival in patients treated mainly with immunochemotherapy plus rituximab. These results also suggest that the addition of rituximab to chemotherapy improves the prognosis associated with EBV detection in DLBCL.

2012-01-01T00:00:00Z Ventura, F Rocha, J Pereira, T Marques, H Pardal, F Brito, C http://comum.rcaap.pt/handle/123456789/2814 2012-11-30T16:04:19Z 2009-01-01T00:00:00Z

Title: Sweet syndrome as the presenting symptom of hairy cell leukemia Authors: Ventura, F; Rocha, J; Pereira, T; Marques, H; Pardal, F; Brito, C

2009-01-01T00:00:00Z Pinheiro, C Longatto-Filho, A Scapulatempo, C Mesquita-Rodrigues, A Alves, VA Schmitt, F Baltazar, F http://comum.rcaap.pt/handle/123456789/2526 2012-09-01T01:14:35Z 2008-01-01T00:00:00Z

Title: Increased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas Authors: Pinheiro, C; Longatto-Filho, A; Scapulatempo, C; Mesquita-Rodrigues, A; Alves, VA; Schmitt, F; Baltazar, F Abstract: Tumour cells are known to be highly glycolytic, thus producing high amounts of lactic acid. Monocarboxylate transporters (MCTs), by promoting the efflux of the accumulating acids, constitute one of the most important mechanisms in the maintenance of tumour intracellular pH. Since data concerning MCT expression in colorectal carcinomas (CRC) are scarce and controversial, the present study aimed to assess the expressions of MCT1, 2, and 4 in a well characterized series of CRC and assess their role in CRC carcinogenesis. CRC samples (126 cases) were analyzed for MCT1, MCT2, and MCT4 immunoexpression and findings correlated with clinico-pathological parameters. Expression of all MCT isoforms in tumour cells was significantly increased when compared to adjacent normal epithelium. Remarkably, there was a significant gain of membrane expression for MCT1 and MCT4 and loss of plasma membrane expression for MCT2 in tumour cells. Plasma membrane expression of MCT1 was directly related to the presence of vascular invasion. This is the larger study on MCT expression in CRC and evaluates for the first time its clinico-pathological significance. The increased expression of these transporters suggests an important role in CRC, which might justify their use, especially MCT1 and MCT4, as targets in CRC drug therapy.

2008-01-01T00:00:00Z