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Neuroendocrine cells are widely distributed throughout the body. They can produce, store, and secrete peptides and biogenic amines. Neuroendocrine tumors (NETs) are rare, but most are found in the intestine, pancreas, and lung. NETs may cause specific hormonal symptoms (eg, carcinoid syndrome) or appear nonfunctional. Blood or urine concentrations of tumor-secreted amines and peptides have been used as biomarkers in the diagnosis and management of NETs. This article focuses on currently available biochemical testing of blood or urine for gastroenteropancreatic and lung NETs and discusses the limitations of these tests and the potential role of newer multianalyte markers for NET management.

To characterize the cell surface receptor for dehydroepiandrosterone (DHEA), we synthesized a DHEA analog containing biotin and benzophenone groups (DHEA–BP–Bt). DHEA–BP–Bt was equipotent with DHEA in competing with [ 3 H]DHEA for binding to solubilized plasma membranes of bovine aortic endothelial cells (BAEC). Additionally, DHEA–BP–Bt pre-conjugated to avidin and immobilized on agarose, also inhibited plasma membrane binding of [ 3 H]DHEA. Furthermore, DHEA–BP–Bt activated endothelial nitric oxide synthase, similar to DHEA. Confocal micrographs showed that, upon photoirradiation, DHEA–BP–Bt bound to sites on the cell surface of BAEC in a DHEA inhibitable manner. Finally, DHEA–BP–Bt bound specifically to proteins of approximately 55 kDa and 80 kDa, either when live cells were UV irradiated with the analog and plasma membrane proteins separated by SDS-PAGE or in a ligand blot analysis. These data confirm the successful synthesis of a photoactive, biotinylated DHEA analog which is capable of cross-linking to and identifying plasma membrane DHEA binding sites and which will allow us to further purify this receptor.

A role for uncoupling protein (UCP) homologues in mediating the proton leak in mammalian mitochondria is controversial. We subjected insulinoma (INS-1) cells to adenoviral expression of UCP2 or UCP1 and assessed the proton leak as the kinetic relationship between oxygen use and the inner mitochondrial membrane potential. Cells were infected with different amounts of rat UCP2, and, in other experiments, with either UCP2 or UCP1. The relative molar expression of these subtypes was quantified through comparison with histidine-tagged UCP1 or UCP2 proteins engineered by expression in Escherichia coli. Adenoviral infection with UCP2, compared with beta-galactosidase, resulted in a dose-dependent shift in kinetics indicating increased H(+) flux at any given membrane potential. UCP1 also enhanced H(+) flux, but, on a relative molar basis, the overexpression of the endogenous protein, UCP2, was more potent than UCP1. These results were not due to nonspecific overexpression of mitochondrial protein since UCP1 activity was inhibited by GDP and because overexpression of another membrane carrier protein, the oxoglutarate malate carrier had no effect. UCP2-mediated H(+) conduction was not GDP sensitive. These data suggest that the UCP homologue, UCP2, mediates the proton leak in mitochondria of a mammalian cell wherein UCP2 is the native subtype.

Efficacy and safety of telotristat ethyl in patients with carcinoid syndrome inadequately controlled by somatostatin analogs : Analysis of the completed TELESTAR extension period