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

Four patients with advanced endocrine malignancies were treated with a somatostatin analogue (SMS 201-995) for palliation of hormone-induced symptoms during 3-6 months. Two had the carcinoid syndrome (one midgut and one foregut), one had medullary thyroid carcinoma and an ectopic ACTH syndrome, and one patient had a metastatic gastrinoma. The carcinoid patients had excellent symptomatic relief with a low dose of the drug, 50 micrograms subcutaneously twice daily, in one case despite progression of tumour disease and biochemical tumour markers. These findings indicate an action of the drug not only on hormonal release but also at peripheral sites. The patient with medullary thyroid carcinoma had relief of gastrointestinal symptoms when the drug dose was increased (100 micrograms twice daily). The levels of ACTH in peripheral blood were reduced, but not the calcitonin levels. The gastrinoma patient had undergone a major pancreatic resection (Whipple procedure) and was treated with omeprazole. SMS 201-995 reduced the peripheral gastrin levels acutely, but during the treatment fasting gastrin values increased, and the tumour growth progressed. Treatment was stopped owing to elevated fasting glucose level, increased steatorrhoea, and clinical attacks of cholangitis. Special attention is advocated for patients with major pancreatic resection and biliary reconstruction, who may be susceptible to physiological effects of somatostatin (or its analogues)--that is, impaired insulin release and decreased motility.
 ...
PMID:The use of a long-acting somatostatin analogue in the treatment of advanced endocrine malignancies with gastrointestinal symptoms. 289 Nov 86

Somatostatin analogue (SMS 201-995) has been shown to decrease total serum gastrin in patients with gastrinoma; however, the gastrin level rarely returns to normal, despite the near-complete inhibition of acid secretion. This implies that SMS may have an inhibitory action on the biologically active molecular species of gastrin and have little effect on biologically inactive species. To test this hypothesis, we determined the effect of SMS on the molecular species of gastrin in eight patients with the Zollinger-Ellison syndrome. Serum obtained before treatment and 6 hours and 18 hours after treatment (SMS 1 microgram/kg, subcutaneously) was sampled and assayed for molecular species of gastrin by means of gel filtration chromatography and fractional quantitation of gastrin species by radioimmunoassay. There was a significant decrease in the amount of G-34 and G-17 species. BBG and G-14 decreased, a change not significant at 6 hours but significant 18 hours after SMS. The distribution of the various molecular species as a percent of total immunoreactive gastrin was analyzed before and after SMS. There was a shift in the distribution of the molecular species, so that 6 hours after SMS treatment nearly 50% of total gastrin activity was accounted for by BBG and component I. SMS seems to have a different potency to inhibit release of the various gastrin molecular species. This observation may explain the failure of total gastrin levels to return to normal after SMS treatment in patients with the Zollinger-Ellison syndrome.
 ...
PMID:Effect of somatostatin analogue (SMS 201-995) on molecular species of gastrin in gastrinoma. 289 Dec 4

Functional gastrin-containing tumor cells (GT cells) have been maintained in short-term culture on microporous membranes, and their response to selected agents has been determined. After dispersion of gastrinoma by collagenase-DNAase digestion coupled with mechanical disruption, dispersed cells were depleted in stromal material by selective attachment to a plastic substrate, then cultured for 72 hours on porous cellulose membranes. Cultures contained 68 +/- 5% GT cells with a viability of 92 +/- 2%. Secretin stimulated the rate of gastrin release from cultured GT cells in both a time- and a dose-dependent fashion. To examine the possible involvement of adenylate cyclase- and protein kinase C-mediated mechanisms in regulating gastrin release from the neoplastic GT cells, we evaluated the effects of 8-bromoadenosine 3':5'-cyclic monophosphate (8-BrcAMP; 10(-4) - 10(-2) mol/L), the diterpene forskolin (10(-5) mol/L), 12-0-tetradencanoylphorobol 13-acetate (TPA; 10(-8) - 10(-6) mol/L), and 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD; 10(-8) - 10(-6) mol/L) on gastrin release. Among all compounds tested, 8-BrcAMP (10(-2) mol/L) was the most potent, stimulating the rate of gastrin release 263% above basal. Both 8-BrcAMP and TPA stimulated gastrin release in a dose-dependent fashion. The biologically inactive phorbol ester, 4 alpha PDD, was without effect at all concentrations. Somatostatin (10(-8) - 10(-6) mol/L) inhibited 8-BrcAMP-stimulated gastrin release in a dose-dependent fashion to a maximum of 75%.
 ...
PMID:Control of gastrin release in cultured gastrinoma-derived G cells. 289 16

We have examined the effects of the somatostatin analogue (SMS 201-995) in 10 patients with gastrinoma syndrome. Four had hepatic metastases, one had a tumor in a peripancreatic lymph node, two had resectable intrahepatic and intraduodenal gastrinomas, and in three the primary tumor was not found. Acutely, SMS 201-995 decreased acid secretion and restored the BAO/MAO ratio to normal in eight of eight patients. Basal and secretin-stimulated gastrin responses were suppressed but not normalized in eight of eight patients. Suppression of endogenous gastrin restored responsiveness to exogenous gastrin. Treatment for up to 12 months with SMS 201-995 controlled symptoms in six of eight patients, suppressed serum gastrin in three of five, and suppressed acid secretion in three of three patients. Treatment with SMS 201-995 in three patients for 5 months decreased tumor secretion of gastrin and diminished basal acid secretion, an effect that persisted in two of three patients 48 hours after withdrawal of SMS. In patients with metastatic disease who had high levels of gastrin, SMS treatment for 5 to 12 months did not inhibit tumor growth or decrease gastrin levels. SMS treatment arrested progression of tumor growth only in patients who had a reduction in gastrin and gastric acid secretion. We conclude that SMS may be useful in the management of gastrinoma patients by decreasing hypersecretion of gastrin and gastric acid and, over a longer term, may even change tumor capacity to release gastrin and gastric acid secretion. SMS may thus be useful as a palliative agent and as an adjunct to conventional treatment of the gastrinoma syndrome. SMS does not appear to shrink tumor mass in patients with very high basal gastrin levels.
 ...
PMID:Somatostatin analogue (SMS 201-995) in patients with gastrinomas. 290 62

Unlike its lethal exocrine counterpart, islet cell carcinoma of the pancreas is an indolent neuroendocrine neoplasm. The majority of these tumors are hormonally active. When functioning, a number of clinical syndromes (for example, hyperinsulinism, Zollinger-Ellison and Cushing's syndromes) may be evident. Fifty-eight patients surgically treated between 1965 and 1984 were retrospectively analyzed. The purpose of this study was to determine the distribution of functioning versus nonfunctioning tumors and the response to type of therapy. Mean postoperative follow-up was 7.4 years. Survival and prognostic indices were calculated by the Kaplan-Meier method and compared with log-rank tests. Of the group, 54% had functioning and 46% nonfunctioning tumors. Gastrinomas were the most common functioning tumors encountered (19%). Of interest was the finding that nonfunctioning tumors increased steadily during the last 15 years of the study (25% to 65%). Curative resections were performed in 15 (26%) and noncurative procedures in 43 patients (74%), with an overall operative mortality rate of 3%. Symptomatic improvement was achieved in 90% (curative) and 51% (noncurative). Survival at 3 years was 87% and 66% for the curative and noncurative groups, respectively (p less than 0.1), with an overall 5-year survival of 42%. The absence of hepatic metastases was a major predictor of survival at 3 years (82% vs 56%, p less than 0.05). Survival was statistically better at 3 years in those patients with gastrinomas compared with patients with nonfunctioning tumors (91% vs 58%, p less than 0.05). Although surgical cure is rare, significant long-term palliation may be achieved in a large percentage of patients with an aggressive surgical approach, occasional total gastrectomy, combination chemotherapy, H2 blockade, when indicated, and, most recently, with the new long-acting analogue of somatostatin.
 ...
PMID:Islet cell carcinomas of the pancreas: a twenty-year experience. 290 80

The number of gastrin cells (G cells) and somatostatin cells (D cells) per surface unit, and the G/D cell ratio were estimated in biopsy specimens of the antrum from normal subjects without hypergastrinemia, and from patients with hypergastrinemia not induced by gastrinoma or supra selective vagotomy. Compared with normal subjects, antral G cell density and G/D cell ratio were significantly increased in patients with hypergastrinemia. A significant correlation was found between G cell density or G/D cell ratio and the integrated gastrin output values. A quantitative estimation appears therefore possible in biopsy specimens.
 ...
PMID:[Hyperplasia of antral "G" cells. Quantitative evaluation in endoscopic biopsies]. 290 2

Zollinger-Ellison syndrome developed in a 46-yr-old woman due to a gastrinoma originating in the proximal jejunum. Resection of the tumor and adjacent lymph nodes containing metastatic carcinoma resulted in prompt reversal of all clinical and biochemical abnormalities, and she remains well 42 mo after surgery. To our knowledge, this patient is one of the first well-documented cases of primary jejunal gastrinoma causing the Zollinger-Ellison syndrome. The tumor contained numerous cells positive for gastrin and smaller numbers positive for serotonin, somatostatin, or bovine pancreatic polypeptide, as diagnosed by immunohistochemistry. In addition, a small subset of tumor cells was positive for growth hormone releasing factor. Our case is the first to document the presence of this neuropeptide in an enteric gastrinoma.
 ...
PMID:Zollinger-Ellison syndrome. Cure by surgical resection of a jejunal gastrinoma containing growth hormone releasing factor. 310 8

We report the first establishment and characterization of functioning gastrinoma from a human being transplanted into nude mice. Tissue was obtained at operation from a gastrinoma liver metastasis from a patient with the Zollinger-Ellison syndrome. The tumor was implanted subcutaneously in five athymic nude mice. Serum gastrin was measured by means of radioimmunoassay in specimens of mouse blood taken before and 5 minutes after intraperitoneal injection of secretin (100 micrograms/kg). In a second experiment serum gastrin was measured 30 minutes after injection of somatostatin analogue, SMS 201-995 (300 micrograms/kg). Studies were also done in 10 control mice. At passage, the fundus of each tumor-bearing mouse was weighed and examined microscopically. The gastrinoma (tumor line, PT) has been maintained for 34 months through four passages with a tumor doubling time of 37 to 45 days. The histology is similar to the original tumor. Immunocytochemistry showed that PT contained gastrin. In two mice metastasis developed 9 months after implantation. Gastrin levels in mice bearing PT have ranged from 216 to 12,000 pg/ml. Gastrin levels of control mice ranged from 0 to 63 pg/ml. Secretin increased gastrin levels in three of five mice tested and decreased gastrin levels in two mice. Repeat secretin tests showed identical results. SMS 201-995 decreased gastrin levels from basal values. Fundic weight of mice bearing PT (397 +/- 93 mg) was significantly greater than control fundic weight (180 +/- 26 mg). Gastrinomas growing in nude mice produce physiologically active gastrin as shown by elevated serum gastrin levels and by hyperplasia of the stomach. Two distinct subpopulations of gastrinoma cells respond differently to secretin. This model should provide important information on mechanisms of growth control and on gastrin release by gastrinomas in human beings.
 ...
PMID:Establishment of a human gastrinoma in nude mice. 319 31

We have studied the concentration of various gastrointestinal peptides in a crude porcine secretin (Boots) preparation and pure natural porcine secretin (GIH, Kabi) preparation. Boots secretin was found to contain 140.3 ng secretin, 1.27 ng human pancreatic polypeptide (hPP), 1.03 ng gastrin, 137.4 ng cholecystokinin (CCK), 241 microU insulin, 1.86 ng vasoactive intestinal polypeptide (VIP), 2.22 ng glucagon and 6.60 ng somatostatin (SRIF) per Crick Harper unit Boots secretin. Sephadex gel filtration demonstrated that the immunoreactivity was due to the hormone per se. GIH secretin contained 240 ng secretin per clinical unit (CU) and less than detectable concentrations of hPP, gastrin, CCK, insulin, VIP, glucagon and SRIF. To determine the clinical significance of having contaminating peptides in Boots secretin, we investigated the effect(s) in 4 subjects. Determined in a highly gastrin-specific assay, the mean plasma gastrin response to Boots secretin administration was slightly, but not significantly greater than the GIH secretin response at 1 and 2.5 minutes. However, in some subjects false positive elevations in plasma gastrin immunoreactivity occurred when some commercially available kit gastrin assays were employed. After intravenous injection of Boots secretin, mean plasma hPP levels rose significantly more than after GIH secretin administration. The mean peak plasma insulin level after GIH secretin administration was significantly higher than after Boots secretin. Neither secretin preparation caused a change in plasma glucose, glucagon and SRIF levels. From these results, it is suggested that GIH secretin be used as the preparation of choice in provocative testing for diagnosing gastrinoma or deficiencies of exocrine pancreatic function.
 ...
PMID:Stimulation of human pancreatic polypeptide and gastrin by Boots and GIH secretin: in vitro and in vivo studies. 355 22

It is now evident that hypersecretion of gastric hydrochloric acid is an important pathogenetic element among a variety of heterogeneous factors responsible for the production of common duodenal ulcer. Hypersecretion of gastric acid due to usually strikingly increased circulating levels of gastrin released from gastrinoma tissue is characteristics of patients with to Zollinger-Ellison Syndrome. In contrast, fasting serum gastrin levels are normal in patients with common duodenal ulcer. The polypeptide hormone, gastrin does, however, appear to play subtle and multiple roles in enhancement of gastric acid secretion in duodenal ulcer. Recent evidence suggests that abnormalities in gastrin release and action may be influenced by participation of somatostatin. The hypothesis is proposed for consideration and for further investigation that the multiple subtle abnormalities in gastrin release and parietal cell sensitivity to gastrin may be due to disturbances in the actions or concentrations of locally acting polypeptides, substances which are capable of suppressing gastrin release and its effects (somatostatin), or alternatively, are capable of stimulating release of gastrin into the circulation (bombesin).
 ...
PMID:The role of gastrin in duodenal ulcer. 611 7


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>