Browsing by Author "Soares, M"
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- Adult B-Cell Acute Lymphoblastic Leukemia Cells Display Decreased PTEN Activity and Constitutive Hyperactivation of PI3K/Akt Pathway Despite High PTEN Protein LevelsPublication . Gomes, AM; Soares, M; Ribeiro, P; Caldas, J; Póvoa, V; Martins, L; Melão, A; Serra-Caetano, A; Botelho de Sousa, A; Lacerda, J; Barata, JAdult B-cell acute lymphoblastic leukemia remains a major therapeutic challenge, requiring a better characterization of the molecular determinants underlying disease progression and resistance to treatment. Here, using a phospho-flow cytometry approach we show that adult diagnostic B-cell acute lymphoblastic leukemia specimens display PI3K/Akt pathway hyperactivation, irrespective of their BCR-ABL status and despite paradoxically high basal expression of PTEN, the major negative regulator of the pathway. Protein kinase CK2 is known to phosphorylate PTEN thereby driving PTEN protein stabilization and concomitant PTEN functional inactivation. In agreement, we found that adult B-cell acute lymphoblastic leukemia samples show significantly higher CK2 kinase activity and lower PTEN lipid phosphatase activity than healthy controls. Moreover, the clinical-grade CK2 inhibitor CX-4945 (Silmitasertib) reversed PTEN levels in leukemia cells to those observed in healthy controls, and promoted leukemia cell death without significantly affecting normal bone marrow cells. Our studies indicate that CK2-mediated PTEN posttranslational inactivation, associated with PI3K/Akt pathway hyperactivation, are a common event in adult B-cell acute lymphoblastic leukemia and suggest that CK2 inhibition may constitute a valid, novel therapeutic tool in this malignancy.
- Cross-Protection to New Drifted Influenza A(H3) Viruses and Prevalence of Protective Antibodies to Seasonal Influenza, During 2014 in PortugalPublication . Guiomar, R; Pereira da Silva, S; Conde, P; Cristóvão, P; Maia, AC; Pechirra, P; Rodrigues, AP; Nunes, B; Milho, L; Coelho, AP; Fernandes, A; Caseiro, P; Rodrigues, F; Correia, L; Pereira-Vaz, J; Almeida, S; Branquinho, P; Côrte-Real, R; Viseu, R; Peres, MJ; Sanches, R; Dantas, F; Freitas, L; Andrade, G; Maurílio, M; Caldeira, F; Cabral Veloso, R; Mota-Vieira, L; Soares, M; Couto, AR; Bruges-Armas, J; Mouro Pinto, R; Sobrinho Simões, J; Costa, MR; Guimarães, JT; Martins, L; Cunha, MINTRODUCTION: Immune profile for influenza viruses is highly changeable over time. Serological studies can assess the prevalence of influenza, estimate the risk of infection, highlight asymptomatic infection rate and can also provide data on vaccine coverage. The aims of the study were to evaluate pre-existing cross-protection against influenza A(H3) drift viruses and to assess influenza immunity in the Portuguese population. MATERIALS AND METHODS: We developed a cross-sectional study based on a convenience sample of 626 sera collected during June 2014, covering all age groups, both gender and all administrative health regions of Portugal. Sera antibody titers for seasonal and new A(H3) drift influenza virus were evaluated by hemagglutination inhibition assay (HI). Seroprevalence to each seasonal influenza vaccine strain virus and to the new A(H3) drift circulating strain was estimated by age group, gender and region and compared with seasonal influenza-like illness (ILI) incidence rates before and after the study period. RESULTS: Our findings suggest that seroprevalences of influenza A(H3) (39.9%; 95% CI: 36.2-43.8) and A(H1)pdm09 (29.7%; 95% CI: 26.3-33.4) antibodies were higher than for influenza B, in line with high ILI incidence rates for A(H3) followed by A(H1)pdm09, during 2013/2014 season. Low pre-existing cross-protection against new A(H3) drift viruses were observed in A(H3) seropositive individuals (46%). Both against influenza A(H1)pdm09 and A(H3) seroprotection was highest in younger than 14-years old. Protective antibodies against influenza B were highest in those older than 65years old, especially for B/Yamagata lineage, 33.3% (95% CI: 25.7-41.9). Women showed a high seroprevalence to influenza, although without statistical significance, when compared to men. A significant decreasing trend in seroprotection from north to south regions of Portugal mainland was observed. CONCLUSIONS: Our results emphasize that low seroprotection increases the risk of influenza infection in the following winter season. Seroepidemiological studies can inform policy makers on the need for vaccination and additional preventive measures.
- Deficiência Femoral Proximal FocalPublication . Soares, M; Teixeira Martins, A; Sant´Anna, F
- Recomendações para Análise Mutacional em Tumores do Estroma Gastrointestinal (GISTs). Grupo de Trabalho Português GIST - Proposta de CondeixaPublication . Lopes, JM; Soares, M; Gouveia, AM; Barroso, S; Cravo, M; Mansinho, H; Penedo, J; Sá, A; Santos, LL; Teixeira, JAOs autores apresentam as recomendações para a análise mutacional de GISTs, aprovadas por unanimidade por um grupo multidisciplinar em 20 de Julho de 2012. O estado mutacional de genes como o KIT e o PDGFRA permite identificar alvos terapêuticos para inibidores da tirosinacínase (ITKs) e, por isso, a boa prática clínica nas decisões bioterapêuticas de doentes com GISTs deve incluir a análise do estado mutacional. A análise mutacional da doença primária não é recomendada na rotina diagnóstica da generalidade dos GISTs; no entanto, pode ter valor prognóstico e ser útil na seleção de doentes, após ressecção completa de GIST primário e é considerada experimental na doença progressiva sob tratamento com ITKs. A análise mutacional deve considerar-se nos casos selecionados descritos neste texto e ser realizada em laboratórios em conformidade com padrões elevados de garantia de qualidade, atendendo ao seu elevado impacto sobre as decisões clínicas.
- The Sequential Organ Failure Assessment (SOFA) Score: Has the Time Come for an Update?Publication . Moreno, R; Rhodes, A; Piquilloud, L; Hernandez, G; Takala, J; Gershengorn, H; Tavares, M; Coopersmith, C; Myatra, S; Singer, M; Rezende, E; Prescott, H; Soares, M; Timsit, JF; de Lange, D; Jung, C; De Waele, J; Martin, G; Summers, C; Azoulay, E; Fujii, T; McLean, A; Vincent, JLThe Sequential Organ Failure Assessment (SOFA) score was developed more than 25 years ago to provide a simple method of assessing and monitoring organ dysfunction in critically ill patients. Changes in clinical practice over the last few decades, with new interventions and a greater focus on non-invasive monitoring systems, mean it is time to update the SOFA score. As a first step in this process, we propose some possible new variables that could be included in a SOFA 2.0. By so doing, we hope to stimulate debate and discussion to move toward a new, properly validated score that will be fit for modern practice.
- The Status of Intensive Care Medicine Research and a Future Agenda for Very Old Patients in the ICUPublication . Flaatten, H; de Lange, DW; Artigas, A; Bin, D; Moreno, R; Christensen, S; Joynt, GM; Bagshaw, SM; Sprung, CL; Benoit, D; Soares, M; Guidet, BThe "very old intensive care patients" (abbreviated to VOPs; greater than 80 years old) are probably the fastest expanding subgroup of all intensive care unit (ICU) patients. Up until recently most ICU physicians have been reluctant to admit these VOPs. The general consensus was that there was little survival to gain and the incremental life expectancy of ICU admission was considered too small. Several publications have questioned this belief, but others have confirmed the poor long-term mortality rates in VOPs. More appropriate triage (resource limitation enforced decisions), admission decisions based on shared decision-making and improved prediction models are also needed for this particular patient group. Here, an expert panel proposes a research agenda for VOPs for the coming years.