RESUMO
Survivin, a member of the inhibitor of apoptosis family of proteins (IAPs) that controls cell division, apoptosis, metastasis and angiogenesis, is overexpressed in essentially all human cancers. As a consequence, the gene/protein is considered an attractive target for cancer treatment. Here, we discuss recent findings related to the regulation of survivin expression and its role in angiogenesis, particularly in the context of hypoxia. We propose a novel role for survivin in cancer, whereby expression of the protein in tumor cells promotes VEGF synthesis, secretion and angiogenesis. Mechanistically, we propose the existence of a positive feed-back loop involving PI3-kinase/Akt activation and enhanced ß-Catenin-TCF/LEF-dependent VEGF expression followed by secretion. Finally, we elaborate on the possibility that this mechanism operating in cancer cells may contribute to enhanced tumor vascularization by vasculogenic mimicry together with conventional angiogenesis.
Assuntos
Proteínas Inibidoras de Apoptose/metabolismo , Neovascularização Patológica/metabolismo , Hipóxia Celular/genética , Hipóxia Celular/fisiologia , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Inibidoras de Apoptose/genética , Espécies Reativas de Oxigênio/metabolismo , SurvivinaRESUMO
Platelet units for transfusion purposes are obtained manually from whole blood or by apheresis, in an automated process. In both methods, platelets during storage present a characteristics grouped under the name "storage lesion" that are associated with adverse effects on platelet units. Oxidative stress has been claimed to be one of major causes, leading to activation and apoptosis processes affecting their post transfusion functionality. In this work, we observed an association between apheresis and a reduced presence of oxidative stress and better results in functional markers in stored platelets, compared to manually obtained platelets. Then, apheresis which would ensure a greater number of functional platelets during the 5 days of storage, compared to concentrates obtained from whole blood.
Assuntos
Plaquetas/metabolismo , Preservação de Sangue , Estresse Oxidativo , Ativação Plaquetária , Plaquetoferese , Adulto , Feminino , Humanos , Masculino , Transfusão de Plaquetas , Fatores de TempoRESUMO
AIM: To study the evolution of impaired fasting glucose (IFG), considering glucose and HbA1c levels and risk factors associated, in a period of 6 years. METHODS: We studied 94 subjects with impaired fasting glucose (IFG) that were diagnosed in 2005 and followed up to 2012. Glucose and HbA1c levels were determined. A descriptive analysis of contingence charts was performed in order to study the evolution in the development of type-2 diabetes mellitus (T2DM). RESULTS: Twenty-eight of ninety-four subjects became T2DM; 51/94 remained with IFG; and 20/94 presented normal fasting glucose. From the 28 diabetic subjects, 9 had already developed diabetes and were under treatment with oral hypoglycemic agents; 5 were diagnosed with plasma glucose < 126 mg/dL, but with HbA1c over 6.5%. In those who developed diabetes, 15/28 had a family history of T2DM in first relative degree. Also, diabetic subjects had a BMI significantly higher than nodiabetics (t test: P < 0.01). The individuals that in 2005 had the highest BMI are those who currently have diabetes. CONCLUSION: The IFG constitutes a condition of high risk of developing T2DM in a few years, especially over 110 mg/dL and in obesity patients.