Somatostatin (Sheep)

Prostaglandins inhibit insulin secretion in a manner similar to that of norepinephrine (NE) and somatostatin. As NE inhibits endocytosis as well as exocytosis we have now examined the modulation of endocytosis by prostaglandin E1(PGE1). Endocytosis following exocytosis was recorded by whole-cell patch clamp capacitance measurements in INS-832/13 cells. Prolonged depolarizing pulses producing a high level of Ca2+influx were used to stimulate maximal exocytosis and to deplete the readily releasable pool of granules (RRP). This high Ca2+influx eliminates the inhibitory effect of PGE1on exocytosis and allows specific characterization of the inhibitory effect of PGE1on the subsequent compensatory endocytosis. After stimulating exocytosis, endocytosis was apparent under control conditions but was inhibited by PGE1in a PTX-insensitive manner. Dialyzing a synthetic peptide mimicking the C-terminus of the α-subunit of the heterotrimeric G-protein Gzinto the cells blocked the inhibition of endocytosis by PGE1whereas a control-randomized peptide was without effect.

Glutathione (GSH)-, somatostatin acetate (ST)- and ovomucoid (OV)-functionalized silica-monolithic stationary phases were designed and synthesized for HILIC and chiral separation using capillary electrochromatography (CEC). GSH, ST and OV were covalently incorporated into the silica skeleton via the epoxy ring-opening reaction between their amino groups and the glycidyl moiety in γ-glycidoxypropyltrimethoxysilane (GPTMS) together with polycondensation and copolymerization of tetramethyloxysilane and GPTMS. Not only could the direction and electroosmotic flow magnitude on the prepared GSH-, ST- and OV-silica hybrid monolithic stationary phases be controlled by the pH of the mobile phase, but also a typical HILIC behavior was observed so that the nucleotides and HPLC peptide standard mixture could be baseline separated using an aqueous mobile phase without any acetonitrile during CEC. Moreover, the prepared monolithic columns had a chiral separation ability to separate dl-amino acids.

Gastro-entero-pancreatic tumors (GEP-NETs) are rare neoplasms often characterized by an overexpression of somatostatin receptors. Thus, radiolabeled somatostatin analogues have showed an increasing relevance both in diagnosis and treatment, especially in low- and intermediate-differentiated GEP-NETs. These evidences have led to a growing development of new functional imaging techniques as 68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) proved useful in the management of these neoplasms. However these tumors have a heterogeneous behavior also modifying their aggressiveness through time. Therefore sometimes 18F-fluorodeoxyglucose PET/CT appears to be more appropriate to obtain a better assessment of the disease. According to these considerations, the combination of different functional imaging techniques should be considered in the management of GEP-NETs patients allowing clinicians to choose the tailored therapeutic approach among available options.

BACKGROUND: Targeted therapies (interferon (IFN), VEGF inhibitors, and somatostatin analogs (SSA)) have become an integral part of the NET treatment paradigm. We systematically review the available literature to assess the overall benefits and harms of targeted therapy on progression-free survival (PFS), overall survival (OS), response rate (RR) and toxicity.