Browsing by Author "Martins, A"
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- Expression, mutation and copy number analysis of platelet-derived growth factor receptor A (PDGFRA) and its ligand PDGFA in gliomasPublication . Martinho, O; Longatto-Filho, A; Lambros, MB; Martins, A; Pinheiro, C; Silva, AI; Pardal, F; Amorim, J; Mackay, A; Milanezi, F; Tamber, N; Fenwick, K; Ashworth, A; Reis-Filho, J; Lopes, JM; Reis, RMBACKGROUND: Malignant gliomas are the most prevalent type of primary brain tumours but the therapeutic armamentarium for these tumours is limited. Platelet-derived growth factor (PDGF) signalling has been shown to be a key regulator of glioma development. Clinical trials evaluating the efficacy of anti-PDGFRA therapies on gliomas are ongoing. In this study, we intended to analyse the expression of PDGFA and its receptor PDGFRA, as well as the underlying genetic (mutations and amplification) mechanisms driving their expression in a large series of human gliomas. METHODS: PDGFA and PDGFRA expression was evaluated by immunohistochemistry in a series of 160 gliomas of distinct World Health Organization (WHO) malignancy grade. PDGFRA-activating gene mutations (exons 12, 18 and 23) were assessed in a subset of 86 cases by PCR-single-strand conformational polymorphism (PCR-SSCP), followed by direct sequencing. PDGFRA gene amplification analysis was performed in 57 cases by quantitative real-time PCR (QPCR) and further validated in a subset of cases by chromogenic in situ hybridisation (CISH) and microarray-based comparative genomic hybridisation (aCGH). RESULTS: PDGFA and PDGFRA expression was found in 81.2% (130 out of 160) and 29.6% (48 out of 160) of gliomas, respectively. Its expression was significantly correlated with histological type of the tumours; however, no significant association between the expression of the ligand and its receptor was observed. The absence of PDGFA expression was significantly associated with the age of patients and with poor prognosis. Although PDGFRA gene-activating mutations were not found, PDGFRA gene amplification was observed in 21.1% (12 out of 57) of gliomas. No association was found between the presence of PDGFRA gene amplification and expression, excepting for grade II diffuse astrocytomas. CONCLUSION: The concurrent expression of PDGFA and PDGFRA in different subtypes of gliomas, reinforce the recognised significance of this signalling pathway in gliomas. PDGFRA gene amplification rather than gene mutation may be the underlying genetic mechanism driving PDGFRA overexpression in a portion of gliomas. Taken together, our results could provide in the future a molecular basis for PDGFRA-targeted therapies in gliomas.
- Molecular alterations of PDGA and PDGFRA in GliomasPublication . Martinho, O; Longatto-Filho, A; Lambros, MB; Martins, A; Pinheiro, C; Silva, AI; Pardal, F; Amorim, J; Mackay, A; Milanezi, F; Tamber, N; Fenwick, K; Ashworth, A; Reis-Filho, JS; Lopes, JM; Reis, RM
- Mutation analysis of B-RAF gene in human gliomas.Publication . Basto, D; Trovisco, V; Lopes, JM; Martins, A; Pardal, F; Soares, P; Reis, RMThe RAS/RAF/MEK/ERK kinase pathway is pivotal in the transduction of mitogenic stimuli from activated growth factor receptors, which regulates cell proliferation, survival, and differentiation. Up-regulation of this pathway due to RAS mutations is found in approximately 30% of human tumors. Recently, activating mutations of B-RAF were identified in a large proportion of human cancers. Gliomas are the most frequent primary central nervous system tumors and the molecular mechanisms that underlie the development and progression of these tumors are far from being completely understood. The purpose of this study was to clarify the incidence of B-RAF mutations and their possible relation with tumor progression in a series of 82 human gliomas, including 49 astrocytic and 33 oligodendroglial tumors. The analysis of B-RAF hotspot regions, exons 11 and 15, showed presence of B-RAF mutations in only 2 out of 34 (6%) glioblastomas, and absence in the remaining histological types. Both mutations were located in the hotspot residue 600 (V600E) at exon 15, which leads to constitutive B-RAF kinase activity. These data suggest that activating mutations of B-RAF are not a frequent event in gliomas; nevertheless, when present they are associated with high-grade malignant lesions.
- Role of central obesity in risk stratification after an acute coronary event: Does central obesity add prognostic value to the Global Registry of Acute Coronary Events (GRACE) risk score in patients with acute coronary syndrome?Publication . Martins, A; Ribeiro, S; Gonçalves, P; Correia, ABACKGROUND: Accurate risk stratification is an important step in the initial management of acute coronary syndrome (ACS), and current guidelines recommend the use of risk scores, such as the Global Registry of Acute Coronary Events risk score (GRACE RS). Recent studies have suggested that abdominal obesity is associated with cardiovascular events in patients with ACS. However, little is known about the additional value of abdominal obesity beyond risk scores. The aim of our study was thus to assess whether waist circumference, a surrogate of abdominal adiposity, adds prognostic information to the GRACE RS. METHODS: This was a retrospective cohort study of ACS patients admitted consecutively to a cardiac care unit between June 2009 and July 2010. The composite of all-cause mortality or myocardial reinfarction within six months of index hospitalization was used as the endpoint for the analysis. RESULTS: A total of 285 patients were studied, 96.1% admitted for myocardial infarction (with or without ST elevation) and 3.9% for unstable angina. At the end of the follow-up period, 10 patients had died and the composite endpoint had been reached in 27 patients (9.5%). More than 70% of the study population were obese or overweight, and abdominal obesity was present in 44.6%. The GRACE RS showed poor predictive accuracy (area under the curve 0.60), and most of the GRACE variables did not reach statistical significance in multivariate analysis. The addition of waist circumference to the GRACE RS did not improve its discriminatory performance. CONCLUSION: Abdominal obesity does not add prognostic information to the GRACE RS to predict six-month mortality or myocardial reinfarction
- Tiroidectomia Total e Hipocalcemia: Análise de 100 casosPublication . Ribas, S; Martins, A; Soares, V; Koch, P
- Treatment planning systems dosimetry auditing project in PortugalPublication . Lopes, MC; Cavaco, A; Jacob, K; Madureira, L; Germano, S; Faustino, S; Lencart, J; Trindade, M; Vale, J; Batel, V; Sousa, M; Bernardo, A; Brás, S; Macedo, S; Pimparel, D; Ponte, F; Diaz, E; Martins, A; Pinheiro, A; Marques, F; Batista, C; Silva, L; Rodrigues, M; Carita, L; Gershkevitsh, E; Izewska, JBACKGROUND AND PURPOSE: The Medical Physics Division of the Portuguese Physics Society (DFM_SPF) in collaboration with the IAEA, carried out a national auditing project in radiotherapy, between September 2011 and April 2012. The objective of this audit was to ensure the optimal usage of treatment planning systems. The national results are presented in this paper. MATERIAL AND METHODS: The audit methodology simulated all steps of external beam radiotherapy workflow, from image acquisition to treatment planning and dose delivery. A thorax CIRS phantom lend by IAEA was used in 8 planning test-cases for photon beams corresponding to 15 measuring points (33 point dose results, including individual fields in multi-field test cases and 5 sum results) in different phantom materials covering a set of typical clinical delivery techniques in 3D Conformal Radiotherapy. RESULTS: All 24 radiotherapy centers in Portugal have participated. 50 photon beams with energies 4-18 MV have been audited using 25 linear accelerators and 32 calculation algorithms. In general a very good consistency was observed for the same type of algorithm in all centres and for each beam quality. CONCLUSIONS: The overall results confirmed that the national status of TPS calculations and dose delivery for 3D conformal radiotherapy is generally acceptable with no major causes for concern. This project contributed to the strengthening of the cooperation between the centres and professionals, paving the way to further national collaborations.