Autologous peripheral retinal pigment epithelium translocation in patients with subfoveal neovascular membranes.

Aim: To evaluate the possibility of translocating autologous peripheral retinal pigment epithelial (RPE) cells and enhance their adhesion to improve functional outcome after choroidal neovascular membrane extraction in patients with subfoveal neovascular membranes.

Methods: A prospective, non-controlled surgical study in eight consecutive patients operated between February and July 2001 with final data monitoring in July 2002. All patients had mixed subfoveal membranes of 2-4 disc diameters.

Crucial role for somatostatin receptor subtype 2 in determining the uptake of [111In-DTPA-D-Phe1]octreotide in somatostatin receptor-positive organs.

Unlabelled: Human somatostatin (SS) receptor (sst)-positive tumors can be visualized by gamma camera scintigraphy after the injection of [(111)In-diethylenetriaminepentaacetic acid (DTPA)-D-Phe(1)] octreotide. Uptake of [(111)In-DTPA-D-Phe(1)]octreotide is dependent on sst-mediated internalization of the radioligand by the tumor cells. Human sst-positive tumors frequently express multiple sst subtypes.

Expression of somatostatin, cortistatin, and somatostatin receptors in human monocytes, macrophages, and dendritic cells.

Increasing evidence suggests that neuropeptides play a role in the regulatory mechanisms between the neuroendocrine and immune systems. A differential expression of the five known somatostatin (SS) receptors (sst1-5) has been demonstrated in human immune cells and tissues. However, little is known concerning regulation and expression of sst1-5 and the peptide SS.

The pathophysiological consequences of somatostatin receptor internalization and resistance.

Somatostatin receptors expressed on tumor cells form the rationale for somatostatin analog treatment of patients with somatostatin receptor-positive neuroendocrine tumors. Nevertheless, although somatostatin analogs effectively control hormonal hypersecretion by GH-secreting pituitary adenomas, islet cell tumors, and carcinoid tumors, significant differences are observed among patients with respect to the efficacy of treatment. This may be related to a differential expression of somatostatin receptor subtypes among tumors.

Cortistatin rather than somatostatin as a potential endogenous ligand for somatostatin receptors in the human immune system.

Cells of the human immune system have been shown to express somatostatin receptors (sst). The expression of sst suggests a functional role of the peptide somatostatin (SS). However, SS expression has not been demonstrated yet in different human immune tissues.

Luteinizing hormone (LH)-responsive Cushing's syndrome: the demonstration of LH receptor messenger ribonucleic acid in hyperplastic adrenal cells, which respond to chorionic gonadotropin and serotonin agonists in vitro.

In a substantial part of adrenal adenomas and hyperplasias from patients with Cushing's syndrome, cortisol production is controlled by the expression of aberrant hormone receptors on adrenocortical cells. We present in vivo and in vitro data of two patients with a LH-responsive Cushing's syndrome based on ACTH-independent bilateral adrenal hyperplasia. Patients 1 and 2 are women who presented with Cushing's syndrome and bilateral adrenal hyperplasia.

Somatostatin receptor gene therapy combined with targeted therapy with radiolabeled octreotide: a new treatment for liver metastases.

Objective: To evaluate the effect of peptide receptor radionuclide therapy (PRRT) on somatostatin receptor (SSR)-transfected colon carcinoma cells in a rat liver metastases model.

Summary Background Data: Previously the authors have shown highly effective therapy with PRRT of SSR-positive tumors. This treatment is SSR-mediated; successful treatment is seen only in SSR-positive tumors, with no effect in SSR-negative tumors.

Selective alkylation and acylation of alpha and epsilon amino groups with PEG in a somatostatin analogue: tailored chemistry for optimized bioconjugates.

The effects of the type and location of polymer grafting on the biological activity of different mono-PEG derivatives of the somatostatin analogue RC160 were evaluated. A chemical strategy to obtain mono-PEG alkylation or acylation of the peptide's alpha-terminal or lysil-epsilon primary amines was devised. Selective BOC protection of the two available primary amines, followed by reaction with two different PEG reagents and removal of the protecting group, was carried out.

Somatostatin analogs in the diagnosis and treatment of cancer.

Over the past few years, significant progress has been made in our understanding of the biology and functional significance of somatostatin receptors (sst) on human tumors. Somatostatin analogs, such as octreotide, bind predominantly to sst(2) and successfully control hormone hypersecretion in patients with acromegaly, islet cell tumors and carcinoids, and (temporary) control of tumor growth is often also seen. Furthermore, sst(2) on tumors can be imaged in vivo after the injection of radionuclide-coupled octreotide.

Quantitative and functional expression of somatostatin receptor subtypes in human thymocytes.

We recently demonstrated the expression of somatostatin (SS) and SS receptor (SSR) subtype 1 (sst1), sst2A, and sst3 in normal human thymic tissue and of sst1 and sst2A on isolated thymic epithelial cells (TEC). We also found an inhibitory effect of SS and octreotide on TEC proliferation. In the present study, we further investigated the presence and function of SSR in freshly purified human thymocytes at various stages of development.

Ghrelin secretion is inhibited by either somatostatin or cortistatin in humans.

Ghrelin possesses endocrine and non-endocrine actions mediated by the GH Secretagogue (GHS)-Receptors (GHS-R). The regulation of ghrelin secretion is still largely unknown. Somatostatin (SRIF) modulates central and gastroenteropancreatic hormonal secretions and functions.

Tissue distribution of octreotide binding receptors in normal mice and strains prone to autoimmunity.

Somatostatin has diverse functions, including immunomodulatory functions. In humans, sites of active inflammation can be visualized by the administration of 111In-DTPA(0)-octreotide, a radiolabelled somatostatin analogue. We wished to establish an animal model for preclinical evaluation of the effects of somatostatin analogues on the immune system.

Sequential ACTH and catecholamine secretion in a phaeochromocytoma.

Objective: We describe a patient with an ACTH-producing phaeochromocytoma who initially presented with hypercortisolism and normal catecholamine concentrations, followed by near-normalisation of ACTH secretion and massive catecholamine secretion. In vitro studies were carried out on the tumour to evaluate the interaction between the tumour cells and normal adrenal cortex.

Methods And Results: A 30-year-old man initially presented with severe hypercortisolism, biochemical evidence of ectopic ACTH production, a tumour in the right adrenal gland without a hyperintense signal on the T2-weighted images at magnetic resonance imaging (MRI) scanning, and normal urinary metanephrine concentrations.

Somatostatin modulates G-CSF-induced but not interleukin-3-induced proliferative responses in myeloid 32D cells via activation of somatostatin receptor subtype 2.

Introduction: Somatostatin, originally identified as a peptide involved in neurotransmission, functions as an inhibitor of multiple cellular responses, including hormonal secretion and proliferation. Somatostatin acts through activation of G-protein-coupled receptors of which five subtypes have been identified. We have recently established that human CD34/c-kit expressing hematopoietic progenitors and acute myeloid leukemia (AML) cells exclusively express SSTR2.

Ghrelin drives GH secretion during fasting in man.

Objectives: In humans, fasting leads to elevated serum GH concentrations. Traditionally, changes in hypothalamic GH-releasing hormone and somatostatin release are considered as the main mechanisms that induce this elevated GH secretion during fasting. Ghrelin is an endogenous ligand of the GH secretagogue receptor and is synthesized in the stomach.

Somatostatin is a selective chemoattractant for primitive (CD34(+)) hematopoietic progenitor cells.

Objective: Somatostatin (SST) is a regulatory peptide with a wide variety of activities in different tissues. SST activates G(alpha i)-protein-coupled receptors of a family comprising five members (SSTR1-5). Despite the broad use of SST and its analogs in clinical practice, the spectrum of activities of SST is incompletely defined.

Somatostatin receptor subtype expression in human tumors.

The presence of functional SSR in tumors has several clinical implications which include the possibility a) to control hormonal hypersecretion and related symptomatology by treatment with SS-analogs, b) to detect SSR positive tumors and their metastases by in vivo SSR scintigraphy, and c) to carry out SSR-targeted radiotherapy using radiolabeled SS-analogs. The majority of SSR positive tumors show a differential expression of somatostatin receptor subtypes, sst2 receptors being the most frequently expressed SSR subtype. The predominant expression of sst2 receptors forms the basis for the successful application of sst2 preferring agonists in the treatment of patients with GH-secreting pituitary adenomas, as well as in patients with carcinoid or islet cell tumors.

Neuroendocrine aspects of immunolymphoproliferative diseases.

Exchange of information occurs between cells of neuroendocrine and immune systems. Neuroendocrine hormones may modulate lymphoid cell activities, including proliferation and mitogenesis, and immune cells may produce neuropeptides as well. Neuropetide Y is synthesized in B-cell leukaemia lymphoblasts, while substance P immunoreactivity has been detected in neoplastic haematological samples of different types of leukaemias.

Systemic ghrelin levels in subjects with growth hormone deficiency are not modified by one year of growth hormone replacement therapy.

Objective: Ghrelin stimulates growth hormone (GH) secretion both in vivo and in vitro. Ghrelin is mainly produced in and released from the stomach but it is probably also produced in the hypothalamic arcuate nucleus. Whether pituitary GH release is under the control of ghrelin from the stomach and/or from the arcuate nucleus is not known.

Acute effect of pegvisomant on cardiovascular risk markers in healthy men: implications for the pathogenesis of atherosclerosis in GH deficiency.

Cardiovascular risk is increased in GH deficiency (GHD). GHD adults are frequently abdominally obese and display features of the metabolic syndrome. Otherwise healthy abdominally obese subjects have low GH levels and show features of the metabolic syndrome as well.

Effects of fasting and pegvisomant on the GH-releasing hormone and GH-releasing peptide-6 stimulated growth hormone secretion.

Objective: Pegvisomant is a mutated GH molecule which prevents functional dimerization and subsequent activation of the growth hormone receptor. Pegvisomant and fasting both lead to GH resistance.

Design And Patients: We performed a double-blind placebo-controlled cross-over study comparing the effects of pegvisomant and fasting on the GH-releasing hormone (GHRH)- and GH-releasing peptide-6 (GHRP-6)-stimulated GH-release before and after 3 days of fasting in 10 healthy lean male subjects.

Neuroendocrine tumor markers.

Tumor markers used in the diagnosis and follow-up of patients with neuroendocrine tumors are in most instances not specific for a given tumor and circulate under normal conditions in the serum, making their use as an early diagnostic tool difficult (low sensitivity). By combining hormone measurements with tissue responsiveness, demonstrations of inappropriate secretions of PTH, insulin, and gastrin during hypercalcemia, hypoglycemia, and hyperacidity, respectively, become highly sensitive and specific diagnostic tests. The application of polyclonal antibodies in RIAs of hormones, such as ACTH, insulin, and gastrin, increase the diagnostic level of hormone measurements in patients with neuroendocrine tumors.

Internalization-defective mutants of somatostatin receptor subtype 2 exert normal signaling functions in hematopoietic cells.

The regulatory peptide somatostatin (SST) acts via a family of G-protein-coupled receptors comprising five subtypes (SSTR1-5). G-protein-coupled receptors activate multiple signaling mechanisms, which variably depend on internalization and intracellular routing of activated receptors. We have recently demonstrated that hematopoietic precursors express SSTR2 and that SST is a chemoattractant for these cells.