Combined treatment by octreotide and everolimus: Octreotide enhances inhibitory effect of everolimus in aggressive meningiomas.

Treatment for recurrent and aggressive meningiomas remains an unmet medical need in neuro-oncology, and chemotherapy exhibits limited clinical activity, if any. Merlin expression, encoded by the NF2 gene, is lost in a majority of meningiomas, and merlin is a negative regulator of mTORC1. The sst2 somatostatin receptor, targeted by octreotide, is highly expressed in meningiomas.

Somatostatin receptor sst2 gene transfer in human prolactinomas in vitro: impact on sensitivity to dopamine, somatostatin and dopastatin, in the control of prolactin secretion.

Objective: As prolactinomas fail to respond to dopamine agonist (DA) in 10-20% of cases, we hypothesized that somatostatin subtype 2 receptor (sst2) overexpression in DA-resistant prolactinomas may enhance suppression of prolactine (PRL) using chimeric agonist (dopastatin) that simultaneously binds sst2 and the dopamine subtype 2 receptor (D2DR).

Design And Methods: PRL suppression by octreotide, sst5 agonist, sst2-D2DR agonist (BIM-23A760 dopastatin) and cabergoline was assessed in primary cultures of seven DA-resistant prolactinomas overexpressing sst2.

Results: sst2 was effectively overexpressed via adenoviral expression in prolactinomas (38.

Expression of somatostatin receptors, dopamine D₂ receptors, noradrenaline transporters, and vesicular monoamine transporters in 52 pheochromocytomas and paragangliomas.

While somatostatin receptors (sst), through somatostatin-radiolabeled analogs, are used, mainly in second line, in the diagnosis and treatment of pheochromocytomas (PCC) and paragangliomas (PGL), the clinical significance of dopamine receptor subtype 2 (D₂) in PCC/PGL is unknown. Indeed, radiolabeled dopamine (DA) analogs such as fluorine 18 ((18)F)-DA, used for positron emission tomography in PCC localization, are mainly correlated to the presence of noradrenaline transporter (NAT) and vesicular monoamine transporters (VMAT) but not to D₂. The aim of this study was to quantitate D₂ and sst expression in 52 PCC/PGL and to compare it with that of 35 gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Somatostatin receptor sst2 decreases cell viability and hormonal hypersecretion and reverses octreotide resistance of human pituitary adenomas.

In human somatotroph adenomas, growth hormone (GH) hypersecretion can be inhibited by somatostatin analogues such as octreotide. Unfortunately, serum GH levels reach normal values in only 60% of treated patients. The decreased sensitivity to octreotide is strongly related to a lower expression of somatostatin receptor sst2.

Somatostatinergic ligands in dopamine-sensitive and -resistant prolactinomas.

Objective: Ten percent of patients with prolactinoma fail to respond with normalization of prolactin (PRL) and tumor shrinkage under dopamine agonist (DA) therapy. The resistance to treatment is linked to a loss of dopamine receptor 2 (D2DR). Prolactinomas express somatostatin (SST) receptor subtypes, SSTR1, 2, and 5.