Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the immunohistochemical and ultrastructural features of three duodenal gangliocytic paragangliomas and compare them with duodenal carcinoid, extra-adrenal paraganglioma, pheochromocytoma, and ganglioneuroma. The gangliocytic paraganglioma is characterized by polygonal or columnar epithelial cells, ganglion cells, and spindle cells. The epithelial cells stained for neurofilament, neuron-specific enolase, pancreatic polypeptide, and somatostatin in three cases; leu-enkephalin, molluskan cardioexcitatory peptide, and vasoactive intestinal peptide in two; and glucagon and insulin in one case each. The ganglion cells were positive for leu-enkephalin, neurofilament, neuron-specific enolase, pancreatic polypeptide, and somatostatin in three cases, and glucagon in one. The spindle cells stained for neurofilament, neuron-specific enolase, and S-100 protein. Although there was some overlap in immunoreactivity between the gangliocytic paraganglioma and the other tumors examined, our data indicate that the gangliocytic paraganglioma is a distinctive lesion. We propose that it is a hyperplastic or neoplastic proliferation of 1) endodermally derived epithelial cells originating from the ventral primordium of the pancreas, 2) neuroectodermal ganglion cells, and 3) neuroectodermal spindle cells (Schwann cells).
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PMID:Duodenal gangliocytic paraganglioma. An immunohistochemical and ultrastructural study and a hypothesis concerning its origin. 257 47

Neuropeptide Y (NPY)- and somatostatin (SS)-like immunoreactivities (LI) were investigated in tumor tissues of one ganglioneuroma (GN), 3 ganglioneuroblastomas (GNB) and one neuroblastoma (NB) by radioimmunoassay. NPY-LI was detected from all 5 tumor tissues (16.4-1247 pmol/g wet tissue). Sephadex G-50 column chromatography and reverse phase high performance liquid chromatography (HPLC) revealed that most of the NPY-LI in tumor extracts was eluted in an identical position to synthetic human NPY except one GNB (case 2). In this case, most of the NPY-LI was eluted in a higher molecular weight region than synthetic human NPY in Sephadex G-50 column chromatography and in a more hydrophobic position in HPLC. SS-LI was detected from 4 tumor extracts except one GNB (case 2) (21.3-787 pmol/g wet tissue). Sephadex G-25 column chromatography and reverse phase HPLC revealed that SS-LI in tumor extracts was eluted just after the void volume and then in the same positions as SS-28 and SS-14. These results suggest that NPY, SS-14 and SS-28 exist in tumor tissues of GN, GNB and NB, and most of the NPY-LI in one GNB was a higher molecular and more hydrophobic form of NPY-LI.
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PMID:Neuropeptide Y- and somatostatin-like immunoreactivities in ganglioneuroma, ganglioneuroblastoma and neuroblastoma. 262 Jun 62

The association of neurofibromatosis and pheochromocytoma is well recognized; more recently, attention has been drawn to links between neurofibromatosis, pheochromocytoma, and ampullary somatostatin-rich carcinoid. Because of this association, the duodenum was explored during a recent laparotomy for resection of bilateral pheochromocytoma in a patient with von Recklinghausen's disease. A clinically unsuspected ampullary tumor was discovered; this proved to be in part a ganglioneuroma and in part a somatostatin-rich carcinoid. This paper presents full details of this carefully investigated and documented case and reviews the recent advances in this field. These studies lead us to conclude that: the clinical association of neurofibromatosis, pheochromocytoma, and D cell carcinoids ("somatostatinomas") of the ampullary region is confirmed; this association may be more common than has been previously thought, and the duodenum should be carefully examined in any patient with neurofibromatosis who undergoes laparotomy for pheochromocytoma.
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PMID:The association of neurofibromatosis, pheochromocytoma, and somatostatin-rich duodenal carcinoid tumor. 287 97

We studied five cases of central nervous system neuronal tumor, one gangliocytoma and four gangliogliomas, both ultrastructurally and immunohistochemically, using antibodies to neuroendocrine markers including tyrosine hydroxylase (TH), serotonin (5HT), somatostatin (SOM), met-enkephalin (MEK), leu-enkephalin (LEK), substance P (SP), gastrin, vasopressin, oxytocin, vasoactive intestinal polypeptide, adrenocorticotropic hormone and calcitonin. In all cases, the presence of dense-core vesicles (60-250 nm) in the neuronal elements was the characteristic ultrastructural finding. Synapses were observed in two cases. Immunohistochemically, variable numbers of neuronal cells showed positive staining for SOM in five cases, TH, MEK and LEK in three cases, and 5HT and SP in one case each. The others were negative. Positive immunoreactivity for multiple markers was shown in all cases. SOM, TH, 5HT and SP were present in the small- to medium-sized cells, while MEK and LEK were almost exclusively confined to the large cells. Our study clearly indicated that these tumors contained neuronal cells which were not homogeneous with regard to neuroendocrine markers.
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PMID:Neuroendocrine markers in central nervous system neuronal tumors (gangliocytoma and ganglioglioma). 292 88

Since the description of the watery diarrhea syndrome by Verner and Morrison 29 years ago, clinical and experimental observations have elucidated the pathophysiology of this disease. Vasoactive intestinal polypeptide (VIP) is produced and released by a tumor of the pancreatic islets or by a tumor of neural crest origin such as a ganglioneuroma. Under normal conditions, current evidence suggests that VIP is a neurotransmitter in the central and peripheral nervous systems and particularly in the peptidergic nervous system. The low VIP plasma concentration observed in healthy subjects is viewed as a neuronal overflow since it has been impossible to ascertain any endocrine role for circulating VIP. Markedly elevated VIP plasma levels in the VIPoma syndrome lead to intestinal secretion with severe secretory diarrhea, resulting in hypovolemia, hypokalemia, and acidosis. These symptoms subside after successful tumor removal. Approximately 50 percent of patients have metastatic spread at the time of diagnosis. For these patients, a new and promising therapeutic modality is available in the form of a subcutaneously administered somatostatin analogue that relieves symptoms through potent inhibition of VIP release from tumor tissue.
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PMID:VIPoma syndrome. 303 22

We report the histological, ultrastructural, and immunocytochemical features of six hypothalamic gangliocytomas associated with pituitary GH cell adenomas and/or acromegaly. In four patients, the gangliocytoma was intrasellar, and no hypothalamic investigation was performed; in two patients, autopsy confirmed hypothalamic involvement. Four patients had a gangliocytoma associated with pituitary GH cell adenoma and acromegaly; electron microscopy demonstrated an intimate association between neurons and adenomatous GH cells. One patient had a gangliocytoma and a GH cell adenoma but no clinical evidence of acromegaly. In the sixth patient, clinical and biochemical acromegaly was manifest, but no pituitary adenoma was demonstrated. Using immunocytochemistry, human pancreatic tumor GRF (hptGRF-40) was localized in the majority of neurons of all six gangliocytomas. The pituitary adenomas and nontumorous adenohypophyses were negative for hptGRF-40. In addition, somatostatin, glucagon, and GnRH were demonstrated within some neurons of several tumors; insulin and gastrin stains were equivocal. These findings confirm previous proposals of production of a GRF by such gangliocytomas. While the significance of other peptides found in some of the tumors is uncertain, the presence of hptGRF-40 in neurons of these gangliocytomas supports the theory that GRF excess is the mechanism responsible for over-production of GH and provides evidence for a syndrome of hypothalamic acromegaly.
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PMID:A case for hypothalamic acromegaly: a clinicopathological study of six patients with hypothalamic gangliocytomas producing growth hormone-releasing factor. 642 59

Neuroblastomas and ganglioneuromas frequently produce somatostatin (SOM) and vasoactive intestinal peptide (VIP), and elevated concentrations in tumour tissue are associated with favourable outcome. Both somatostatin and VIP have been shown to have an autocrine effect on tumour growth and differentiation in vitro, and VIP may cause clinical symptoms when released systemically. Using gel-permeation chromatography and specific radioimmunoassays, we further characterised somatostatin-like immunoreactivity (SOM-LI) and VIP-like immunoreactivity (VIP-LI) in neuroblastoma and ganglioneuroma tumour tissue. The major part of SOM-LI and VIP-LI in both neuroblastoma and ganglioneuroma represents the biologically active forms SOM-28, SOM-14 and VIP-2, respectively. 21 children with neuroblastoma and ganglioneuroma were monitored with serial plasma samples during surgery. In 8 children with measurable concentrations of SOM-LI, all showed increased concentrations during tumour manipulation (P = 0.004) that subsequently decreased below preoperative levels in all but one case (P = 0.06). The only child presenting with diarrhoea showed the highest preoperative plasma VIP-LI in the study (54 pmol/l). 2 children with increased concentrations of VIP-LI preoperatively showed a rapid decrease after surgical tumour removal. These findings indicate a systemic release from the tumours. It is concluded that plasma and tumour tissue from children with neuroblastoma and ganglioneuroma contain biologically active molecular forms of somatostatin and vasoactive intestinal peptide. These peptides may bear significance both for specific symptoms in certain patients as well as influencing tumour growth and differentiation in vivo.
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PMID:Somatostatin and vasoactive intestinal peptide (VIP) in neuroblastoma and ganglioneuroma: chromatographic characterisation and release during surgery. 757 50

Two cases of duodenal gangliocytic paraganglioma were studied by means of immunocytochemical methods using 41 kinds of antibodies. The tumors consisted of three histological types; carcinoid, ganglioneuroma and paraganglioma. Tumors of both cases exhibited immunoreactivity to at least one or as many as three of the following: calcitonin, calcitonin-gene related peptide, endocrine granule constituent, Leu7, neuropeptide Y and basic fibroblast growth factor. In addition, these tumors were also immunopositive for neuron specific enolase, S-100 protein, neurofilament protein, pancreatic polypeptide, chromogranin A, somatostatin, leuenkephalin, substance P and vasoactive intestinal peptide, as has been described in previous reports. In one case, tumor cells were immunopositive for adrenocorticotropin, bombesin, gastrin releasing peptide, myelin basic protein, neuroendocrine marker and tyrosine hydroxylase. Moreover, paraganglioma cells of tumors showed both argyrophilia and argentaffinity. These results suggest that duodenal gangliocytic paraganglioma may originate from embryonic neuroinsular complex.
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PMID:Two cases of duodenal gangliocytic paraganglioma: immunocytochemical characteristics. 882 94

Neuroblastoma is a pediatric cancer for which a cure is elusive for most children with disseminated disease. Neuroblastomas possess receptors for somatostatin (SS). Some SS analogues can inhibit their proliferation. In addition, when SS analogues were used as agents for scintigraphy, neuroblastoma tumor sites can be localized with high efficiency. In this study, to better characterize the SS receptor subtype(s) (sst1-5) present in primary tumors and metastases of neuroblastoma, we show that: (1) The ligand 125I-Tyr11-SS-14 binding on membrane proteins from primary tumors and metastases of neuroblastoma cell line IGR-N-91 developed in nude mice shows similar values of Kd (in order of 0.1 nM) and Bmax (in order of fmol/mg) by filter-retention assay. These data are close to those measured on two other neuroblastoma cell lines: SK-N-SH and IGR-N-835 or to that measured on the rat cerebral cortex. (2) The IGR-N-91 sublines derived from primary tumor and metastases show one major complex of 57 kD by the chemical cross-linking assay using the ligands: 125I-SS-14 and 125I-BIM23014. One similar major complex of 57 kD was also detected in SK-N-SH and IGR-N-835 or in the cerebral cortex. (3) Addition of excess nonlabeled peptides selective for sst2 (BIM23014, BIM23060, BIM23068) suppressed the formation of the complex 57 kD whereas addition of BIM23052 or BIM23056 (sst5 and sst3 selective respectively) does not. This pharmacological profile corresponds to sst2. (4) Only RNA message of sst2 gene is detected in IGR-N-91 cells and its metastases derived sublines by reverse-transcription-polymerase chain reaction and Northern hybridization in keeping with the presence of sst2. (5) In human biopsies, the complex of 57 kD corresponding to sst2 is consistently detected in three samples of the histological subset of the disease: benign ganglioneuroma, ganglioneuroblastoma and immature neuroblastoma. Therefore, the sst2 should be considered as the primary target to develop more potent SS analogues for neuroblastoma therapy or/and scintigraphy.
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PMID:Somatostatin-14 mainly binds the somatostatin receptor subtype 2 in human neuroblastoma tumors. 905 84

Neuroblastoma, a childhood tumour of the sympathetic nervous system, may in some cases differentiate to a benign ganglioneuroma or regress due to apoptosis. Somatostatin may inhibit neuroblastoma growth and induce apoptosis in vitro and was therefore investigated. Using a radioimmunoassay, we found that all ganglioneuromas contained high somatostatin concentrations (> 16 pmol/g), significantly higher than neuroblastomas (n = 117, median 2.8 pmol/g), healthy adrenals, Wilms' tumours, phaeochromocytomas and other neuroendocrine tumours (P < 0.001). Neuroblastomas contained more somatostatin than control tumours (P < 0.001-0.05). Neuroblastomas amplified for the MYCN oncogene contained less somatostatin than non-amplified tumours (1.2 pmol/g versus 4.0 pmol/g, respectively; P = 0.026). In a clinically unfavourable neuroblastoma subset (age > 12 months, stage 3 or 4) 16 children with high concentrations of somatostatin in primary tumours had a better prognosis than 23 with low somatostatin (46.7% versus 0% survival at 5 years, P < 0.005). Scintigraphy using 111In-pentetreotide identified tumours expressing high-affinity somatostatin receptors in vivo. However, no significant correlation was found between somatostatin receptor expression and peptide content in 15 tumours. Similarly, human SH-SY5Y neuroblastoma xenografts grown in nude rats showed low somatostatin concentrations, but were positive for somatostatin receptor scintigraphy. Treatment of these rats with the somatostatin analogue octreotide seemed to upregulate in vivo receptor expression of somatostatin and vasoactive intestinal peptide more effectively than 13-cis retinoic acid. In conclusion, somatostatin in neuroblastoma is associated with differentiation to benign ganglioneuromas in vivo and favourable outcome in advanced tumours. Furthermore, somatostatin receptor scintigraphy may identify tumours with high-affinity receptors in children that might benefit from targeted therapy using synthetic somatostatin analogues.
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PMID:Somatostatin in neuroblastoma and ganglioneuroma. 951 58


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