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Chile T.,Laboratory for Cellular and Molecular Endocrinology LIM 25 | Correa-Giannella M.L.,Laboratory for Cellular and Molecular Endocrinology LIM 25 | Fortes M.A.H.Z.,Laboratory for Cellular and Molecular Endocrinology LIM 25 | Bronstein M.D.,Neuroendocrine Unit | And 3 more authors.
Journal of Endocrinological Investigation | Year: 2011

Background: Pituitary tumors account for approximately 10-15% of intracranial neoplasms. Aim: Using the cDNA microarray method, we have previously compared expression under two distinct conditions: a pool of 4 clinically non-functioning pituitary adenomas (NFPA) and a spinal cord metastasis of a non-functioning pituitary carcinoma, in order to gain biological insights into genomic changes of pituitary neoplasias. In the present study, we further investigated the mRNA expression of 3 selected genes previously described as being involved in other neoplasias based on a series of 60 pituitary adenomas: CRABP1 (cellular retinoic acid binding protein 1), GRP (gastrin-releasing peptide), and RERG (Ras-related, estrogen-regulated, growth inhibitor). Material and methods: The expression of CRABP1, GRP, and RERG was determined by quantitative RT-PCR. Results: A significantly higher content of CRABP1 mRNA was observed in NFPA compared to functioning adenomas, and PRL-secreting adenomas showed a lower expression of this gene compared to normal pituitary. A lower expression of GRP mRNA was detected in NFPA compared to normal pituitary and also to functioning adenomas. RERG mRNA was overexpressed in NFPA in comparison to functioning adenomas and to normal pituitary. Among the functioning adenomas, only the ACTH-secreting adenomas presented a higher expression of RERG mRNA compared to normal pituitary. Conclusions: The findings of differential expression of CRABP1 in prolactinomas and of RERG in NFPA compared to normal pituitary suggests that retinoic acid and estrogen receptor, respectively, could be involved in the tumorigenesis of these adenomas subtypes. Additional studies are required to further confirm this hypothesis. ©2011, Editrice Kurtis. Source


Purpose: To test the performance of dual-energy computed tomography (CT) in the assessment of marrow adipose tissue (MAT) content of the lumbar spine by using proton (hydrogen 1 [1H]) magnetic resonance (MR) spectroscopy as a reference standard and to determine the influence of MAT on the assessment of bone mineral density (BMD). Materials and Methods: This study was institutional review board approved and complied with HIPAA guidelines. Written informed consent was obtained. Twelve obese osteopenic but otherwise healthy subjects (mean age 6 standard deviation, 43 years 6 13) underwent 3-T 1H MR spectroscopy of the L2 vertebra by using a point-resolved spatially localized spectroscopy sequence without water suppression. The L2 vertebra was scanned with dual-energy CT (80 and 140 kV) by using a dual-source multi-detector row CT scanner with a calibration phantom. Mean basis material composition relative to the phantom was estimated in the L2 vertebra. Volumetric BMD was measured with and without correction for MAT. Bland-Altman 95% limits of agreement and Pearson correlation coefficients were calculated. Results: There was excellent agreement between 1H MR spectroscopy and dual-energy CT, with a mean difference in fat fraction of 20.02 between the techniques, with a 95% confidence interval of 20.24, 0.20. There was a strong correlation between marrow fat fraction obtained with 1H MR spectroscopy and that obtained with dual-energy CT (r = 0.91, P , .001). The presence of MAT led to underestimation of BMD, and this bias increased with increasing MAT content (P , .001). Conclusion: Dual-energy CT can be used to assess MAT content and BMD of the lumbar spine in a single examination and provides data that closely agree and correlate with 1H MR spectroscopy data. © RSNA, 2015. Source


John B.J.,Neuroendocrine Unit | Davidson B.R.,Neuroendocrine Unit
Expert Review of Gastroenterology and Hepatology | Year: 2012

Hepatic metastases develop in 85% of patients with gastroenteropancreatic neuroendocrine tumors. Radical surgery, which involves resection of the primary and liver metastases, is the mainstay of treatment, with 60-70% 5-year survival and 35% 10-year survival rates. However, less than 15% of neuroendocrine tumor liver metastases (NETLMs) are resectable, owing either to multifocality or the inability to preserve sufficient parenchyma following resection. This article deals with the therapeutic modalities available for nonresectable liver metastases, and the therapeutic options available for management of nonresectable NETLMs are discussed. Targeted therapies for NETLMs include hepatic artery embolization, transcatheter arterial chemoembolization, radiolabeled/drug-eluting microspheres, radiofrequency ablation, cryoablation and phenol injection. Hepatic artery embolization/transcatheter arterial chemoembolization is associated with 75-100% symptom relief and an objective tumor response varying from 33 to 80%. Other modalities, such as biotherapy, peptide receptor therapy and chemotherapy, target both the primary and metastatic disease. Their effects on NETLMs as a subgroup have not been evaluated. Various therapeutic options are available for the treatment of unresectable NETLMs. Most offer significant symptomatic relief, with only a few comparative studies showing survival benefit. Most of the available evidence is based on retrospective and prospective case series rather than randomized controlled trials. Well-designed studies on existing treatment modalities and the search for newer therapeutic options are required. © 2012 Expert Reviews Ltd. Source


Doknic M.,Neuroendocrine Unit | Stojanovic M.,Neuroendocrine Unit | Popovic V.,Neuroendocrine Unit
Pediatric Endocrinology Reviews | Year: 2014

Background: Growth hormone (GH) treatment currently requires years of treatment. Maintaining full compliance with daily injections has been difficult. Teens have the highest rate of non-concordance (missing injections 1-2 per week). In adults the rate of low concordance (low IGF1) rises with each year of treatment. Improving compliance to GH therapy by less burdensome means of GH replacement can be achieved either by changing GH delivery frequency (weekly, monthly) or by changing injection device characteristics (minimal preparation, easy setting, minimal pain, automatic needle insertion, needle free devices).Long acting formulations: Long-acting forms of GH have been developed either as sustained-release preparations of GH (Nutropin-depot, which has been withdrawn in 2004 and LB 03002 once weekly GH, which has received a positive opinion by CHMP of EMA in early 2013) or as the conjugated analogues which prolong the half life of GH. Currently a variety of modified GH molecules which delay GH clearance (CTP modified GH, recombinant polypeptide XTEN, GH conjugated with albumin, GH linked to immunoglobulin) are studied and the ongoing studies are in different phases (from I-III). Each of these preparations has been tested in experimental animal models.Efficacy and safety: Although different types of formulations have been studied, all are pharmacokinetically and pharmacodynamically effective in extending GH action and result in prolonged increase in IGF-I concentrations. Clinical data are available for once-weekly sustained-release GH treatment and the data show beneficial effects in adults with GH deficiency over a 12 month period and adequate growth rate in pre-pubertal children with GH deficiency over the period of three-years.Conclusions: Clinical data are still very limited. Available short term studies show that treatment with long-acting GH preparation is effective and safe in GH deficient children and adults. A different physiology underlies the long-acting GH and we still need to improve our knowledge about these formulations of GH. Long-term studies are needed to confirm the value and safety (greater exposure to GH) of these agents. Source


Perello M.,Neuroendocrine Unit | Giovambattista A.,Neuroendocrine Unit | Castrogiovanni D.,Neuroendocrine Unit | Gaillard R.C.,University of Lausanne | Spinedi E.,Neuroendocrine Unit
NeuroImmunoModulation | Year: 2011

The aim of this study was to evaluate the effect of ovariectomy on the acute-phase response of inflammatory stress. Ex vivo adrenocortical, peripheral mononuclear cell (PMNC) and adipocyte activities were studied in intact and ovariectomized mice. Endotoxemia was mimicked by intraperitoneal administration of bacterial lipopolysaccharide (LPS; 25 mg per mouse) to sham-operated and 21-day ovariectomized mice. Circulating corticosterone, tumor necrosis factor-α (TNFα) and leptin concentrations were monitored before and 30-120 min after the administration of LPS. Additionally, in vitro experiments were performed with isolated corticoadrenal cells, PMNCs and omental adipocytes from sham-operated and ovariectomized mice incubated with specific secretagogues. The results indicate that while ovariectomy enhanced TNFα secretion after in vivo administration of LPS, it reduced corticoadrenal response and abrogated LPS-elicited leptin secretion into the circulation. While the corticoadrenal sensitivity to ACTH stimulation was reduced by ovariectomy, the LPS-induced PMNC response was not affected. Exogenous leptin enhanced baseline PMNC function regardless of surgery. Finally, ovariectomy drastically reduced in vitro adipocyte functionality. Our data support the notion that ovariectomy modified neuroendocrine-immune-adipocyte axis function and strongly suggest that ovarian activity could play a pivotal role in the development of an adequate immune defense mechanism after injury. Copyright © 2010 S. Karger AG, Basel. Source

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