Serum tumour markers in germ cell tumours: From diagnosis to cure.

Germ cell tumors (GCTs) represent the best and the only example of solid tumors curable in the large majority of patients. GCTs are one of the few malignancies for which specific biochemical markers have been identified: human chorionic gonadotropin (HCG) and alfa-fetoprotein (AFP). Due to their specificity and sensitivity they constitute formidable tools in the diagnosis and monitoring of treatment for GCTs. As a tumor mass marker, lactate dehydrogenase (LDH) is also considered. Tumor markers are expressed in 15-20% of seminoma and 60-80% of non-seminoma. With the aim to increase sensitivity and specificity, recent studies have proposed miRNAs as serum biomarkers. This review will focus on role of serum tumor markers in diagnosis, staging, prognosis, monitoring of response, and finally follow-up of GCTs.

Different modulation of dipeptidyl peptidase-4 activity between microvascular and macrovascular human endothelial cells.

Dipeptidyl peptidase 4 (DPP-4) is an enzyme that is produced by endothelial cells in different districts and circulates in plasma. Patients with type 2 diabetes show a reduction in active Glucagon-Like Peptide-1 (GLP-1) that could be due to impairment of secretion or its degradation or both. GLP-1 is rapidly inactivated in vivo, mainly by the DPP-4. Some authors suggest that Metformin has no direct inhibitory effect on DPP-4 activity and that Metformin and the other biguanides enhance GLP-1 secretion; others suggest a possible role of Metformin in the inhibition of the DPP-4 activity. In order to better elucidate the role of insulin sensitizers on the modulation of GLP-1 circulating levels, DPP-4 activity and mRNA expression were measured in cultured human aortic endothelial cells (HAEC) and human microvascular dermal endothelial cells (HMVEC) exposed to high glucose, Metformin and Rosiglitazone. Present data show that hyperglycemia is capable of increasing in a significant manner the DPP-4 activity only in microvascular endothelial cells. Rosiglitazone is able to modulate in a negative manner the expression of DPP-4 but not its activity in macrovascular endothelial cells, while at 24 h of exposure it is able to increase significantly DPP-4 activity but not its expression in microvascular endothelial cells. Metformin at 48 h only in microvascular endothelial cells is able to reduce in a significant manner (p = 0.01) the activity of DPP-4 but not its expression. The modulation of DPP-4 is site specific.

Adipokines as possible new predictors of cardiovascular diseases: a case control study.

Background and Aims. The secretion of several adipocytokines, such as adiponectin, retinol-binding protein 4 (RBP4), adipocyte fatty acid binding protein (aFABP), and visfatin, is altered in subjects with abdominal adiposity; these endocrine alterations could contribute to increased cardiovascular risk. The aim of the study was to assess the relationship among adiponectin, RBP4, aFABP, and visfatin, and incident cardiovascular disease. Methods and Results. A case-control study, nested within a prospective cohort, on 2945 subjects enrolled for a diabetes screening program was performed. We studied 18 patients with incident fatal or nonfatal IHD (Ischemic Heart Disease) or CVD (Cerebrovascular Disease), compared with 18 matched control subjects. Circulating adiponectin levels were significantly lower in cases of IHD with respect to controls. Circulating RBP4 levels were significantly increased in CVD and decreased in IHD with respect to controls. Circulating aFABP4 levels were significantly increased in CVD, while no difference was associated with IHD. Circulating visfatin levels were significantly lower in cases of both CVD and IHD with respect to controls, while no difference was associated with CVD. Conclusions. The present study confirms that low adiponectin is associated with increased incidents of IHD, but not CVD, and suggests, for the first time, a major effect of visfatin, aFABP, and RBP4 in the development of cardiovascular disease.

Dipeptidyl peptidase-IV expression and activity in human glomerular endothelial cells.

Glucagon-like peptide-1 (GLP-1), a meal-stimulated gastrointestinal insulinotropic hormone inactivated by dipeptidyl peptidase-IV (DPP-IV), is reduced in type 2 diabetic patients. The present study shows that 2-week exposure of human glomerular endothelial cells to high glucose (22 mM) determines a highly significant increase in DPP-IV activity and mRNA expression, which cannot be entirely accounted for by hyperosmolarity. On the other hand, incubation of purified DPP-IV in a buffer solution added with high glucose does not affect enzyme activity. These results suggest that high glucose increases expression and activity of DPP-IV, possibly contributing to GLP-1 reduction in type 2 diabetic patients.