Myxoma or Lung Cancer? / ¿Mixoma o cáncer de pulmón?

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[BRAF gene mutation in the natural history of papillary thyroid carcinoma: diagnostic and prognostic implications]. / Mutação do gene BRAF na história natural do carcinoma papilar da tireóide: implicações diagnósticas e prognósticas.

The papillary carcinoma is the most prevalent malignant neoplasm of the thyroid gland, representing 85-90% of all cases, and its incidence has been increasing in recent years. It is relatively indolent, however other types poorly differentiated or anaplastic, are more aggressive and usually associated with poor prognosis. Approximately half of these papillary carcinomas harbor a thymine-to-adenine transversion (T1799A) point mutation, in the gene encoding the serine/threonine-kinase B-type Raf kinase (BRAF), with substitution of valine by glutamate (V600E). Mutated BRAF, generates a constitutive activation of the mitogen-activated protein kinases (MAPK) signaling pathway, which plays a critical role in transmitting proliferative signals generated by cell surface receptors and cytoplasmic signaling elements, to the nucleus. BRAF mutation is mutually exclusive with other common genetic alterations, supporting its independent oncogenic role in cell proliferation, survival and tumor de-differentiation. The BRAFV600E occurs exclusively in papillary thyroid carcinoma and papillary carcinoma-derived anaplastic cancer, rising as a specific diagnostic marker for this tumor when identified in cytological / histological exams. This mutation has recently emerged, as a potential prognostic marker for papillary thyroid carcinoma, after several studies have found this mutation to be associated with some clinicopathological characteristics, known to predict tumor recurrence and progression, including, for instance, old patient age, extrathyroidal invasion and lymph node metastasis. It is therefore considered a marker of aggressive disease in these tumors, associated with increased cancer recurrence and even loss of radioiodine avidity. Several studies were not able to confirm these associations. It has become clearer that BRAF mutation will likely have significant impact on the clinical management of papillary thyroid carcinoma.

[Oxidative stress and its effects on insulin resistance and pancreatic beta-cells dysfunction: relationship with type 2 diabetes mellitus complications]. / Stress oxidativo e seus efeitos na insulino-resistência e disfunção das células Beta-pancreáticas: relação com as complicações da diabetes mellitus tipo 2.

Type 2 diabetes mellitus, the most prevalent and serious metabolic disease worldwide, is believed to result from the interaction between genetical and lifestyle factors. In genetically predisposed people, the combination of a hypercaloric ingestion and reduced physical activity is responsible for the appearance of insulin resistance. This state can be overcomed, until a certain point, with increments of insulin secretion (hyperinsulinemia). However, an insufficient compensation leads to a state of glucose intolerance, which can evolve to diabetes, according to actual knowledge. The noxious effects of the hyperglycemia, allied with the possible increase of free fatty acids, are mediated by highly reactive molecules, oxygen and nitrogen free radicals species (ROS and RNS). Recent data suggests that these reactive species are signalling molecules and are involved in the regulation of the cellular function, being its increased production or reduced elimination a cause of oxidative stress. Indeed, those free radicals act directly through oxidative damage on macromolecules (proteins, lipids, DNA) or indirectly, activating single transduction pathways sensible to stress mechanisms. In this review, we will consider the pathways recognized as the more significant in stress mechanisms, namely: NF-kB, JNK/SAPK, p38 MAPK, PKC, AGE/RAGE, hexosamines and poliol. These signalling cascades are believed to be responsible for the insulin resistance and reduced insulin secretion, therefore the use of innocuous antioxidant substances such as vitamin C, E and the a-lipoic acid, is seen as a possible step for type 2 diabetic complications management. We will also discuss acetylsalicylic acid potentialities in the above-mentioned pathologies.