248 research outputs found
Loss of expression of the oncosuppressor PTEN in thyroid incidentalomas associates with GLUT1 plasmamembrane expression
No full textAIM: Molecular imaging diagnosis with FDG-PET ((18)F-fluorodeoxyglucose positron emission tomography with computed tomography) can reveal the presence of un-suspected thyroid cancer that are referred to as "incidentaloma" because of the incidental finding. The glucose analogue (18)FDG is internalized in the cells by glucose transporters belonging to the GLUTs family. The surface expression of GLUT is under the control of the PI3k/Akt pathway. PTEN is an oncosuppressor frequently mutated or deleted in thyroid cancers. The lipid phosphatase activity of wild type PTEN switches off the Akt pathway. Here we tested the hypothesis that PTEN expression might affect the surface expression of GLUT1 and therefore influence the possibility of "incidental" detection of thyroid cancer based on FDG-PET.
METHODS:
The biopsy of 8 patients, who were incidentally diagnosed with PTC by (18)F-fluorodeoxyglucose positron emission tomography with computed tomography, was assayed by immunofluorescence for the co-expression of the PTEN oncosuppressor and of GLUT1.
RESULTS:
Loss of PTEN expression was detected in the majority of investigated cases (N.=6/8). Strikingly, while the two PTEN positive cases were negative for GLUT1 expression, the PTEN negative cases showed intense expression of GLUT1 at the cell surface.
CONCLUSION:
The present observations, though made in a limited number of cases, suggest that PTEN negative thyroid cancers have high chances to be revealed as incidentalomas at FDG-PET
Ghrelin: more than a new frontier in neuroendocrinology.
No full textGhrelin, a peptide predominantly produced by the stomach, has been discovered as natural ligand of the growth hormone secretagogue receptor (GHS-R) type 1a. More recently, ghrelin attracted enormous interest as new orexigenic factor. However, ghrelin exerts several other neuroendocrine, metabolic and also non-endocrine actions (e.g. cardiovascular activities) that are explained by the widespread distribution of ghrelin and GHS-R expression. The existence of GHS-R subtypes and evidence that neuroendocrine but not all other ghrelin actions are dependent on acylation in serine 3 add further complexity to the system whose major physiological role remains to be definitely clarified. What we are learning from the studies about the control of ghrelin secretion is that it is mostly under metabolic control; the most important impact of ghrelin would, in turn, be metabolic. However, a recent study states that the ghrelin knockout (KO) mouse is not anorectic dwarf and this evidence clearly depicts a remarkable difference from the leptin KO mouse. Nevertheless, the original and fascinating ghrelin story as well as its potential pathophysiological implications in endocrinology and internal medicine are not definitely canceled by this evidence. Besides potential clinical implications for natural or synthetic ghrelin analogues acting as agonists or antagonists, open questions that are waiting for an answer are: how many are the ghrelin receptors? Is ghrelin the or a GHS ligand, i.e. are there other natural GHS-R ligands? Is there a functional balance between acylated and unacylated ghrelin forms that would play different actions? Within the next years these questions will find the appropriate answer and we'll know about the ghrelin system something more precise; this knowledge will more appropriately clarify the potential clinical perspectives
Ghrelin: from somatotrope secretion to new perspectives in the regulation of peripheral metabolic functions.
No full textGhrelin, a peptide predominantly produced by the stomach, has been discovered as natural ligand of the GH secretagogue (GHS) receptor type 1a (GHS-R1a), suggesting the existence a new endogenous modulator of somatotrope secretion. Subsequently, ghrelin turned out to exert pleiotropic actions, consistent with the widespread distribution of ghrelin and GHS-R expression in central and peripheral tissues. Despite that the binding to GHS-R1a requires ghrelin to be acylated in serine 3, some ghrelin actions are independent of such acylation; thus suggesting the possibility of the existence of other GHS-R subtypes. Ghrelin secretion (70% in its unacylated form) is mainly under metabolic control being modulated by glucose, insulin and feeding. On the other hand, ghrelin influences energy metabolism acting both as a central orexigenic factor and directly on the endocrine pancreas, liver and adipose tissue. Recently, another gastric hormone derived from the same ghrelin gene has been isolated and named obestatin. Obestatin in rats resulted in reduced food intake, jejunal contraction and body weight gain, via specific distinct receptors. Thus, all these data indicate that we are exploring a very complex system deeply involved in the modulation of metabolic functions, whose understanding will probably increase our knowledge about diabetes mellitus and the metabolic syndrome
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