Effects of somatostatin and its analogues on progenitor mesenchymal cells isolated from human pituitary adenomas

Purpose: Progenitor mesenchymal cells (PMCs) have been found also in epithelial tumors and may derive from cancer stem cells (CSCs) by EMT mechanism. In this scenario, the effects of traditionally drugs on PMCs become of primary concern for therapeutic approaches. Previously, we isolated PMCs from acromegalic (GHomas) and not-functioning pituitary adenomas (NFPAs). Here we evaluate: (1) the role of EMT on their origin; (2) the presence of the somatostatin receptors (SSTR1-5); (3) the effects of somatostatin (SST) and its analogues (SSAs) on PMCs proliferation, apoptosis and SSTR1-5 expression. Methods: PMCs were isolated from GHomas and NFPAs; the expression of E-CADHERIN and TGFβRII (referred to EMT), the expression of the SSTR1-5 as well as the proliferation and apoptosis were tested before and after drugs administration. Results: Results show a decrease of E-CADHERIN and an increase of TGFβRII, confirming an EMT involvement; SSTR1-5 are more expressed by PMCs from GHomas than from NFPAs. SST and SSAs administration does not affect cell proliferation and SSTR1-5 expression on PMCs from NFPAs while in PMCs from GHomas, cell proliferation showed a marked decrease and a corresponding increase in the expression of SSTR1-2. Apoptosis rate and EMT were not affected by drugs administration. Conclusions: Results indicate as EMT may be related to the presence of PMCs on pituitary tumors; SSAs, currently used in the management of human GHomas, exert anti-proliferative effect also in PMCs that, because of their derivation from CSCs, may be a new meaningful target for drugs treatment

Vagus nerve stimulation: clinical experience in drug-resistant pediatric epileptic patients.

Vagus nerve stimulation (VNS) is an effective alternative treatment for patients with partial refractory epilepsy. Nevertheless, information regarding VNS in children is still limited.The clinical efficacy, safety and neuropsychological effects of VNS in 34 children (mean age 11.5 years) with drug-resistant epilepsy were studied. Mean follow-up was 30.8 months. Nine patients have been diagnosed with Lennox-Gastaut Syndrome, nine patients were affected by severe partial epilepsy with bisynchronous EEG and drop attacks, and 16 patients suffered from partial epilepsy without bisynchronous EEG and fall seizures. Forms were designed for prospective data collection on each patient's history, seizures, implants, device settings, quality of life (QOL), neuropsychological assessment and adverse events. Surgical technique was performed both by standard two incisions and single neck incision.Mean reduction in total seizures was 39\% at 3 months, 38\% at 6 months, 49\% at 12 months, 61\% at 24 months and 71\% at 36 months. Significant better results were obtained in partial epilepsy, with and without drop attacks, than in Lennox-Gastaut syndrome--three patients being seizure-free. No operative morbidity was reported. Side-effects were minor and transient--the most common were voice alteration and coughing during stimulation. In two patients, electrode breakage occurred 3 years after surgical procedure; in both cases, a new device was implanted after removing the vagal electrode coils and generator.VNS can be considered an appropriate strategy as an add-on treatment in children affected by drug-resistant partial epilepsy and ineligible for resective epilepsy surgery