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Somatostatin analogues inhibit in vitro cell proliferation via specific membrane receptors (SSTRs). Recent studies on transfected cell lines have shown a ligand-induced formation of receptor dimers. The aim of this study is 1) to evaluate the role of specific ligands in modulating receptor interactions in the androgen-dependent prostate cancer cell line, LNCaP, and in the non-small cell lung cancer line, Calu-6, by co-immunoprecipitation and immunoblot; and 2) to correlate the antiproliferative effect of these compounds with their ability in modulating receptor interactions. In LNCaP, we have demonstrated the constitutive presence of sstr1/sstr2, sstr2/sstr5, sstr5/dopamine (DA) type 2 receptor (D2R), and sstr2/D2R dimers. BIM- 23704 (sstr1- and sstr2-preferential compound) increased the co-immunoprecipitation of sstr1/sstr2 and significantly inhibited proliferation (K30.98%). BIM-23244 (sstr2-sstr5 selective agonist) significantly increased the co-immunoprecipitation of sstr2/sstr5, and induced a K41.36% inhibition of proliferation. BIM-23A760, a new somatostatin/DA chimeric agonist with a high affinity for sstr2 and D2R and a moderate affinity for sstr5, significantly increased the sstr5/D2R and sstr2/D2R complexes and was the most powerful in inhibiting proliferation (K42.30%). The chimeric compound was also the most efficient in modulating receptor interaction in Calu-6, increasing the co-immunoprecipitation of D2R/sstr5 and inhibiting cell proliferation (K30.54%). However, behind BIM-23A760, BIM-53097 (D2R-preferential compound) also significantly inhibited Calu-6 proliferation (K17.71%), suggesting a key role for D2R in receptor cross talk and in controlling cell growth. Indeed, activation of monomeric receptors did not affect receptor co-immunoprecipitation, whereas cell proliferation was significantly inhibited when the receptors were synergistically activated. In conclusion, our data show a dynamic ligand-induced somatostatin and DA receptor interaction, which may be crucial for the antiproliferative effects of the new analogues. [ABSTRACT FROM AUTHOR]

The article describes the case of a female Gordon Setter dog which was diagnosed with pancreatic islet cell tumor that secretes insulin-like growth factor type II. Among the symptoms presented by the dog are progressive weakness and ataxia. A pancreatic lesion was revealed by abdominal ultrasound. The dog was treated with prednisone and high-protein diet.

Objective Lanreotide Autogel® 120 mg (ATG120; Ipsen S.p.A, Milan, Italy) is a high-dose, sustained-release aqueous gel formulation, supplied in a prefilled syringe and given by deep subcutaneous injection. The aim of this study was to compare efficacy and tolerability of ATG120 given every 4–8 weeks with those of octreotide LAR (o-LAR) given every 4 weeks. Design patients and intervention A phase III multicentre Italian open clinical study of 23 acromegalic patients (15 female, 8 male). All patients had received o-LAR for 6–18 months and, after 3 months wash out, ATG120 was given every 6 weeks for a total of four injections (Period 1). Then the interval between ATG120 injections was adjusted according to three different schemes: every 4, 6 or 8 weeks depending on GH levels (GH > 2·5 µg/l; 1 < GH ≤ 2·5 µg/l; GH ≤ 1 µg/l, respectively). ATG120 was given for a further two to three doses, with a final assessment (Period 2) at Week 34, 36 or 42. Measurements Hormonal (GH and IGF-I) and clinical efficacy and tolerability. Results ATG120 induced a significant GH decrease from 9·9 ± 11·3 at baseline (Visit 1) to 3·5 ± 5·7 at the end of Period 1 ( P < 0·01) and to 3·8 ± 5·7 µg/l at the final visit ( P < 0·01). IGF-I also decreased from 544 ± 312 at baseline (Visit 1) to 318 ± 181 at Period 1 and to 356 ± 187 µg/l at the final visit (both P < 0·05 vs. baseline). The frequency of ATG120 administrations was adjusted to every 4 weeks in 12 patients, every 6 weeks in 4 patients and every 8 weeks in 6 patients; 1 patient withdrew before the dose adjustment. Serum GH and IGF-I achieved at the end of Period 1 and Period 2 were similar to those reached with o-LAR. The number of patients who achieved GH < 2·5 µg/l was comparable between o-LAR (43%) and ATG120 at Period 1 (48%) and at Period 2 (62%). Normal IGF-I levels were recorded in 8 patients during o-LAR (35%), 11 during ATG Period 1 (48%) and 10 at the final visit (43%). Last, 4 patients showed a better response to ATG120 and 2 to o-LAR. Conclusions Lanreotide Autogel 120 mg is an effective and well-tolerated therapy for acromegaly. In approximately half of patients ATG120 may be administered every 6–8 weeks, instead of every 4 weeks, without lost of efficacy. [ABSTRACT FROM AUTHOR]

Abstract Background The control of growth and nutritional status in the foetus and neonate is a complex mechanism, in which also hormones produced by adipose tissue, such as adiponectin and leptin are involved. The aim of this study was to evaluate levels of adiponectin, leptin and insulin in appropriate (AGA) and small for gestational age (SGA) children during the 1st year of life and to correlate these with auxological parameters. Methods In 33 AGA and 29 SGA infants, weight, length, head circumference, glucose, insulin, adiponectin and leptin levels were evaluated at the second day of life, and at one, six and twelve months, during which a portion of SGA could show catch-up growth (rapid growth in infants born small for their gestational age). Results Both total and isoform adiponectin levels were comparable between AGA and SGA infants at birth and until age one year. These levels significantly increased from birth to the first month of life and then decreased to lower values at 1 year of age in all subjects. Circulating leptin concentrations were higher in AGA (2.1 ± 4.1 ng/ml) than in SGA neonates (0.88 ± 1.03 ng/ml, p < 0.05) at birth, then similar at the 1st and the 6th month of age, but they increased in SGA from six months to one year, when they showed catch-up growth. Circulating insulin levels were not statistically different in AGA and SGA neonates at any study time point. Insulin levels in both AGA and SGA infants increased over the study period, and were significantly lower at birth compared to one, six and 12 months of age. Conclusions During the first year of life, in both AGA and SGA infants a progressive decrease in adiponectin levels was observed, while a difference in leptin values was correlated with the nutritional status.

Introduction: In the last decade, GEP-NET nomenclature has been twice reviewed. The 2000 WHO classification had poor prognostic power in well-differentiated (WD) neoplasms which led to the introduction of two new important parameters: grade and stage, by ENETS; the former became part of the new 2010 WHO classification. Aim(s): Considering the recent introduction of grade and stage, their external validation has been called for in the literature. Since these are important tools in the management of patients, our aim was to reclassify retrospectively with grade and stage our series and correlate with follow-up. Materials and methods: From the histopathology archive at our center, 170 GEPNETs (1993-2011) were identified. Until now, 50 patients have been reclassified. Mean age at diagnosis was 56 years, F:M ratio was 1:1.2 and mean follow-up was 56 months (2-196). Results: Correlating differentiation with overall survival (OS), WD NETs had a strikingly better outcome with respect to poorly differentiated ones. However, only grade identified a subgroup of patients with WD lesions with less favorable clinical behavior (OS at 5 yrs: G1 - 96% v. G2 - 50%). Stage was also useful though not statistically significant in our small series. Conclusion: Our series confirms the importance of grade and stage in prognostic stratification. Retrospective classification of patients who may not have been previously graded or staged may influence the choice of therapeutic options in the future. [ABSTRACT FROM AUTHOR]

Highlights: [•] Somatostatin system plays a significant role in the progression of human prostate cancer. [•] Activation of SS1R and SS2R/SS5R leads to relevant antiproliferative effect. [•] SS1R, SS2R and SS5R are differently distributed among lysosomes and microsomes. [•] SS1R and the SS2R/SS5R dimer represent potential novel targets for the treatment of late-stage prostate cancer. [ABSTRACT FROM AUTHOR]