Browsing by Author "Silva, G"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
- Development of Dl1.72, a Novel Anti-DLL1 Antibody with Anti-Tumor Efficacy against Estrogen Receptor-Positive Breast CancerPublication . Silva, G; Sales-Dias, J; Casal, D; Alves, S; Domenici, G; Barreto, C; Matos, C; Lemos, AR; Matias, AT; Kucheryava, K; Ferreira, A; Moita, MR; Braga, S; Brito, C; Cabral, MG; Casalou, C; Barral, DC; Sousa, PM; Videira, PA; Bandeiras, TM; Barbas, AAberrant Notch signaling is implicated in several cancers, including breast cancer. However, the mechanistic details of the specific receptors and function of ligand-mediated Notch signaling that promote breast cancer remains elusive. In our studies we show that DLL1, a Notch signaling ligand, is significantly overexpressed in ERα+ luminal breast cancer. Intriguingly, DLL1 overexpression correlates with poor prognosis in ERα+ luminal breast cancer, but not in other subtypes of breast cancer. In addition, this effect is specific to DLL1, as other Notch ligands (DLL3, JAGGED1, and JAGGED2) do not influence the clinical outcome of ERα+ patients. Genetic studies show that DLL1-mediated Notch signaling in breast cancer is important for tumor cell proliferation, angiogenesis, and cancer stem cell function. Consistent with prognostic clinical data, we found the tumor-promoting function of DLL1 is exclusive to ERα+ luminal breast cancer, as loss of DLL1 inhibits both tumor growth and lung metastasis of luminal breast cancer. Importantly, we find that estrogen signaling stabilizes DLL1 protein by preventing its proteasomal and lysososmal degradations. Moreover, estrogen inhibits ubiquitination of DLL1. Together, our results highlight an unexpected and novel subtype-specific function of DLL1 in promoting luminal breast cancer that is regulated by estrogen signaling. Our studies also emphasize the critical role of assessing subtype-specific mechanisms driving tumor growth and metastasis to generate effective subtype-specific therapeutics.
- Loop diuretic discontinuation in chronic heart failure patients: A retrospective studyPublication . Silva, G; Moura, B; Moreira, E; Camila Dias, C; Sousa Pinto, B; Campelo, M; Amorim, S; Martins, E; Pinto, R; Maia Araújo, P; Resende, CX; Mena, B; Grácio, T; Teixeira, A; Silva Cardoso, JIntroduction and objectives: The use of loop diuretics is central in managing congestion in heart failure (HF), but their impact on prognosis remains unclear. In euvolemic patients, dose reduction is recommended, but there is no recommendation on their discontinuation. This study aims to assess the impact of loop diuretic discontinuation on the prognosis of outpatients with HF with reduced ejection fraction. Methods: This retrospective cohort study collected data from medical records of patients followed in an outpatient HF clinic at a university hospital center. Patients were included if they had been on loop diuretics and these were discontinued. Demographic, clinical and laboratory data were collected, and number and type of congestive events during the one-year period after discontinuation were recorded. Results: Among 265 patients on loop diuretics, almost half (129) discontinued them at some point. Patients had optimized medical therapy, low median age, low New York Heart Association class, low B-type natriuretic peptide values, normal blood pressure, controlled heart rate and kidney function within normal limits. Among 122 patients with one year of follow-up, 18 (14.8%) had a congestive event. Fifteen events (83.3%) were low-dose diuretic reinitiation at a scheduled visit. There were only three worsening heart failure events (2.5%) during the one-year period. A significant improvement in kidney function from discontinuation to the one-year follow-up appointment was also observed. Conclusions: In our cohort, loop diuretic discontinuation was possible and safe in a large proportion of patients. The results should be interpreted with caution and cannot be extrapolated to a broader population of HF patients.
- Metabolic Profile and Cardiovascular Risk in a Population of Renal transplant recipientsPublication . Gonçalves, M; Vieira, P; Resende, L; Durães, J; Rosa, N; Teixeira, JA; Silva, GIntroduction. Cardiovascular disease is more common in renal transplant recipients (RTRs) than in the general population, and is the major cause of both graft loss and patient death in RTRs. Objectives. This study aimed to characterize the cardiovascular risk factors, calculate the 7-year risk for major adverse cardiac events and the 7-year risk for death in a population of RTRs using a cardiovascular risk calculator, and determine the main cardiovascular risk factors associated with increased prediction of major adverse cardiac event (MACE) and death. Patients. This is a retrospective review of clinical data from 121 RTRs who are in follow-up programs at our institution, and who had a functioning and stable graft for longer than 6 months. Results. Among 121 adult patients followed at our institution (59.5% males, mean age of 49.6 13.8 years, mean times for functioning grafts were 105 73.5 mo), 86.8% had hypertension, 19.8% had diabetes, 24.8% were current or former smokers, 61.9% had increased body mass index, and 71% had dyslipidemia. The 7-year risk for MACE was more than 10% in 38 (31.4%) patients with age, diabetes, and smoke being independent risk predictors. The 7-year risk for death was more than 10% in 56 (46.3%) patients with age, diabetes, blood pressure, smoking, and male gender being independent risk predictors. Conclusion. There is a high prevalence of cardiovascular risk factors in a population of RTRs, and there is increased risk for MACE and death. Accurate risk prediction is important for physician decision support and patient education, promoting improved cardiovascular health of RTRs, and thus prolonging the survival of both patients and graft.