Browsing by Author "Peixoto, Joana"
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- High VEGFA expression Is associated with improved progression-free survival after Bevacizumab treatment in recurrent GlioblastomaPublication . Alves, Bárbara; Peixoto, Joana; Macedo, Sofia; Pinheiro, Jorge; Carvalho, Bruno; Soares, Paula; Lima, Jorge; Lima, Raquel T.Glioblastoma (GB) is a deadly tumor that demands for relevant biomarkers, particularly regarding patients’ response to treatment. MMP-2, MMP-9, VEGFA, and YKL40 are important molecules, given their implication in the infiltrative and angiogenic phenotype of GBs. The purpose of this study was to assess the relationship between the expression of MMP-2, MMP-9, VEGFA, and YKL40 in GB tissues and the patients’ response to temozolomide (first-line treatment) or bevacizumab (second-line treatment). Our results showed that increased VEGFA is significantly associated with an improved response to bevacizumab, while having no correlation with the response to temozolomide. Additionally, YKL40 expression may also be important regarding information about the extent of antiangiogenic treatment in GB patients.
- Study of the relevance of antioxidant enzymes in thyroid cancerPublication . Freitas, Sílvia; Peixoto, Joana; Máximo, Valdemar; Soares, PaulaThyroid cancer(TC) is the most common endocrine malignancy, arising from follicular and parafollicular cells. Oxidative stress, caused by excess reactive oxygen species(ROS) and metabolites, influences TC development and progression, as the thyroid is highly exposed to ROS. The redox balance is maintained by antioxidant enzymes (SOD, GPX) and non-enzymatic antioxidants, which limit ROS formation and detoxify metabolites. Dysregulation of this balance is observed in various TC types(papillary, follicular, medullary, anaplastic). However, the role of antioxidants in TC progression, prognosis, and therapy remains under study. This project aims to explore the correlation between antioxidant enzyme expression and clinicopathological factors to address their role in TC. A series of 90 TC samples were collected, corresponding to benign and malignant lesions. The protein expression pattern of superoxide dismutase 1(SOD1), superoxide dismutase 2(SOD2) and glutathione peroxidase 1(GPX1) was optimized and assessed by immunohistochemistry in formalin-fixed paraffin-embedded samples for this cohort. In addition, the mRNA expression of SOD1, SOD2 and GPX1 are underway by quantifying mRNA expression using real-time quantitative PCR(qPCR). Our series comprise the following histotypes: Multinodular Follicular Disease(2.2%), follicular adenoma(17.8%), fetal adenoma(7.8%), papillary thyroid carcinoma (PTC)(31.1%) - classic PTC(5.6%) and follicular variant of PTC(11.1%) - follicular thyroid carcinoma(12.2%), oncocytic carcinoma(1.1%), medullary thyroid carcinoma(3.3%) and others(26.7%). QuPath evaluation of immunohistochemical analyses are underway being validated by a specialized pathologist. In parallel, qPCR analysis is ongoing. Clinicopathological parameters will be correlated with the expression patterns of the analyzed molecules. We expect to disclose the expression of antioxidant enzymes in TC and assess their potential as diagnostic and prognostic biomarkers.
- TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomasPublication . Melo, Miguel; Gaspar Da Rocha, Adriana; Vinagre, João; Batista, Rui; Peixoto, Joana; Tavares, Catarina; Celestino, Ricardo; Almeida, Ana; Salgado, Catarina; Eloy, Catarina; Castro, Patrícia; Prazeres, Hugo; Lima, Jorge; Amaro, Teresina; Lobo, Cláudia; Martins, Maria João; Moura, Margarida; Cavaco, Branca; Leite, Valeriano; Cameselle-Teijeiro, José; Carrilho, Francisco; Carvalheiro, Manuela; Maximo, Valdemar; Sobrinho-Simões, Manuel; Soares, PaulaContext: Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers. Objectives: We aimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTCs). Design: This was a retrospective observational study. Setting and Patients: We studied 647 tumors and tumor-like lesions. A total of 469 patients with FCDTC treated and followed in five university hospitals were included. Mean follow-up (±SD) was 7.8 ± 5.8 years. Main Outcome Measures: Predictive value of TERT promoter mutations for distant metastasization, disease persistence at the end of follow-up, and disease-specific mortality. Results: TERT promoter mutations were found in 7.5% of papillary carcinomas (PTCs), 17.1% of follicular carcinomas, 29.0% of poorly differentiated carcinomas, and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumors were older (P < .001) and had larger tumors (P = .002). In DTCs, TERT promoter mutations were significantly associated with distant metastases (P < .001) and higher stage (P < .001). Patients with DTC harboring TERT promoter mutations were submitted to more radioiodine treatments (P = .009) with higher cumulative dose (P = .004) and to more treatment modalities (P = .001). At the end of follow-up, patients with TERT-mutated DTCs were more prone to have persistent disease (P = .001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P < .001)] in DTCs (P < .001), PTCs (P = .001), and follicular carcinomas (P < .001). After adjusting for age at diagnosis and gender, the hazard ratio was 10.35 (95% confidence interval 2.01–53.24; P = .005) in DTC and 23.81 (95% confidence interval 1.36–415.76; P = .03) in PTCs. Conclusions: TERT promoter mutations are an indicator of clinically aggressive tumors, being correlated with worse outcome and disease-specific mortality in DTC. TERT promoter mutations have an independent prognostic value in DTC and, notably, in PTC.