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)

Primary neoplasms arising in the liver (3 cases), skin (3 cases) and larynx (2 cases) were studied with a combination of light microscopy, immunohistochemical and electron microscopic techniques. Clinically, only one case exhibited a hormonal syndrome (Zollinger-Ellison) while another had elevated levels of calcitonin in the serum. By light microscopy only one tumour appeared characteristically neuroendocrine ('carcinoid'). The other cases showed variable patterns of small to intermediate size cell carcinomas at times admixed with exocrine appearing areas. Immunoperoxidase studies showed reactivity for various peptides including gastrin, calcitonin, somatostatin and ACTH. Several tumours were positive for more than one peptide. Electron microscopy revealed variable populations of neurosecretory type granules either in the main cytoplasmic mass or in cytoplasmic processes. We conclude that some 'undifferentiated' neoplasms from the aforementioned sites may prove to have neuroendocrine differentiation if the proper techniques are applied to their study. Clinical hormonal syndromes appear to be rare in these tumours;s however, determination of various amine and/or peptide materials, or possibly their metabolites, may be valid aids for their recognition and monitoring. The structural patterns of these tumours are very variable and may include cells with squamous features as well as exocrine differentiation with occasionally prominent production of mucosubstances.
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PMID:Neuroendocrine neoplasms in unusual primary sites. 727 96

Among endocrine tumors arising in the intestinal tract, midgut argentaffin EC cell carcinoids, duodenal gastrin cell tumors and rectal trabecular L cell carcinoids, in order of decreasing frequency, are those better represented. Together they account for more than 80% of such tumors. Duodenal somatostatin cell tumors, gangliocytic paragangliomas and poorly differentiated neuroendocrine carcinomas, are also well defined tumor entities. The carcinoid syndrome with intermittent flushing, hypotension and diarrhea, and the Zollinger-Ellison syndrome with severe peptic ulcer disease, are the only hyperfunctional syndromes consistently found in association with these tumors. The carcinoid syndrome arises in about 10% of intestinal carcinoids, usually in their advanced metastatic stage. The Zollinger-Ellison syndrome occurs in association with about 40% of gastrin cell tumors, including small intramural growths. Tumor prognosis depends on mode and site of presentation, histology, cell type(s), size, level of invasion, metastases (especially distant metastases) and associated clinical syndrome or background disease.
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PMID:Endocrine tumors of the small and large intestine. 747 53

In a 66-year old woman, who suffered from recurrent melena, diarrhea and hematemesis with multiple untreatable gastric and duodenal ulcers, a markedly increased basal and secretin-stimulated gastrin level, clinically a Zollinger-Ellison syndrome was assumed. The conventional diagnostic procedures (esophago-gastro-duodenoscopy, colonoscopy, endosonography, ERCP, abdominal CT and small bowel enema) had failed to reveal the localisation of any gastrinoma. The thereupon performed scintigraphy with In-111-pentetreotide showed four somatostatin receptor expressing liver lesions: two of them could be detected at first site in the consecutively performed MR scans, another retrospectively bearing in mind the scintigraphic images. Today, the somatostatin receptor imaging seems to be a highly sensitive procedure for detecting and localizing hormonally active gastroenteropancreatic tumors. At the same time it is a method for in vivo evaluation of the somatostatin receptor status of localized GEP tumors, thus delivering a decisive diagnostic step for the evaluation of the effectiveness of a therapy with somatostatin analogues before such an expensive therapy is started.
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PMID:[Somatostatin receptor scintigraphy in neuroendocrine tumors exemplified by a patient with hepatic metastases of gastrinoma]. 751 13

Duodenal gastrinomas are now more frequently recognized as the source of hypergastrinemia in patients with Zollinger-Ellison syndrome. The cell lineage of duodenal gastrinomas may differ from that of pancreatic gastrinomas, which accounts for variations in their clinical behavior. Attempts to localize the submucosal tumors are difficult and are limited by their small size. Intraoperative endoscopic transillumination, selective intra-arterial secretin injection, and duodenotomy with mucosal eversion are currently the most sensitive and reliable methods of localization. Endoscopic ultrasonography and somatostatin scintigraphy further enhance the accuracy of preoperative localization of these tumors. Current information based on cure rates and survival data mandates a primary surgical approach in patients with either the sporadic or the multiple endocrine neoplasia type 1-associated form of the disease. Thus, wide local resection of duodenal gastrinomas with removal of all tumor-bearing lymphatic tissue and acid inhibitory pharmacotherapy (proton pump inhibition) may yield 5-year survival rates of 80% to 90%. Similarly, in patients with pancreatic and duodenal gastrinomas as a manifestation of multiple endocrine neoplasia type 1, the additional enucleation of pancreatic lesions with or without distal pancreatectomy has resulted in cure rates of 67% to 100%.
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PMID:Recent advances in the localization and surgical management of duodenal gastrinomas. 758 48

The enterochromaffin-like (ECL) cell of the oxyntic, acid-secreting mucosa is at present the most extensively studied endocrine cell type in the gastrointestinal tract. It is functionally related to acid secretion through paracrine release of histamine. Its ability to undergo proliferation in response to the trophic stimulus of hypergastrinemia has important implications in pathology, being involved in the development of ECL-cell carcinoid tumors of rodents treated with powerful inhibitors of acid secretion as well as in that of most human gastric carcinoids which, with rare exceptions, are composed of ECL cells. The various aspects of the ECL-cell response to hypergastrinemia in humans are discussed in this review. The trophic effect of gastrin is specific for ECL cells and its sensitivity is enhanced by the female sex and by the genetic background of the multiple endocrine neoplasia type 1 (MEN-1) syndrome. Exposure of ECL cells to hypergastrinemia induces peculiar changes in the structure of cytoplasmic granules and triggers the phenotypic expression of a novel protein, the alpha subunit of glycoprotein hormones, absent in normal cells. The ECL-cell hyperplasia driven by hypergastrinemia may influence the hypersecretory gastric state of patients with Zollinger-Ellison syndrome (ZES) by inappropriate intramucosal secretion of histamine and may contribute to the high circulating levels of basic fibroblast growth factor (bFGF), an ECL-cell product responsible for parathyroid mitogenic effects in MEN-1 patients. However, hypergastrinemia per se cannot promote evolution of hyperplasia into carcinoid tumors, for which additional unknown factors, particularly associated with atrophic gastritis or MEN-1 syndrome, are required. ECL-cell carcinoids developing within these backgrounds have a strikingly more favorable course than their gastrin-independent counterpart. Suppression of hypergastrinemia, either by antrectomy or treatment with somatostatin analogues, may induce regression of both ECL-cell hyperplasia and gastrin-sensitive ECL-cell carcinoids.
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PMID:Hypergastrinemia and gastric enterochromaffin-like cells. 776 39

Neuroendocrine gut and pancreatic tumors are neoplasms that present distinct features from other malignant tumors. Firstly, in most patients, tumor growth is rather slow, and even in advanced metastatic disease, there is very little impairment of the general well-being of the individual, e.g. appetite and weight. Secondly, these tumors are known to produce specific peptide hormones which may be factors in some clinical conditions e.g. carcinoid, Zollinger-Ellison and hypoglycemic syndromes. These conditions can be critical to the patients and can occasionally be lethal. Therefore, the treatment of neuroendocrine tumors must control the clinical symptoms related to hormone over-production and prevent further tumor growth. These two features are not always in parallel. Systemic treatment of neuroendocrine tumors mainly consists of chemotherapy, interferon and somatostatin analog administration. Chemotherapy has been used for at least 30 years; the most effective combination has proved to be streptozotocin with 5-fluorouracil or adriamycin. This combination produces biochemical responses in up to 60% of patients with endocrine pancreatic tumors; the results in carcinoid patients are very poor and response rates are < or = 10%. Alpha-interferon (IFN-alpha) produces biochemical responses in approximately 50% of patients with malignant carcinoid tumors, significant reductions in tumor size in 15% and a further 39% of patients have disease stabilization with no further tumor growth. Somatostatin analogs have only been used clinically within the last 10 years, but produce symptomatic improvement in 70% of cases, biochemical responses in 40-60%, but rarely produce any significant reduction in tumor size. These analogs are particularly useful to control severe clinical symptoms and are the first-line therapy for the management of carcinoid patients both peri- and intra-operatively. Patients with endocrine pancreatic tumors, particularly those with glucagon and vasointestinal peptide-producing tumors, benefit most from this type of treatment. Recently, a combination of IFN-alpha and a somatostatin analog has showed an additive effect of these two drugs. The side effects of streptozotocin and 5-fluorouracil are mainly nausea and vomiting which can be controlled with 5-HT3 receptor blocker therapy. Another significant adverse reaction is impaired renal function. The adverse reactions to IFN-alpha are mainly flu-like symptoms, fatigue, mild impairment of liver and bone marrow function and autoimmune reactions in 15% cases. Somatostatin analog treatment causes a low frequency of adverse reactions, those which do occur include gall stone formation and steatorrhea. Future systemic treatment should be based on increased knowledge of the tumor biology, particularly growth-regulatory mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endocrine tumors of the gastrointestinal tract: systemic treatment. 785 82

In patients with the Zollinger-Ellison syndrome, which is either sporadic or integrated into multiple endocrine neoplasia type 1, accurate localization of all the tumours is difficult and may have therapeutic implications. In an attempt to improve this localization, somatostatin receptor scintigraphy using [111In-DTPA-D-Phe1]-octreotide was performed prospectively in 48 consecutive patients with the Zollinger-Ellison syndrome. Thirty of them had the sporadic type of this disease. Scintigraphic data were compared with data obtained by conventional imaging methods, and also, in 32 selected patients, with those obtained by endoscopic ultrasonography. Somatostatin receptor scintigraphy showed abnormal tracer uptake in 39 patients (81%), in whom it correctly identified 50 of the 60 tumoral sites (83%) previously localized by the other imaging methods. In 17 patients (35%) somatostatin receptor scintigraphy disclosed abnormal tracer uptake at 18 different tumoral sites: 14 were located in the abdomen, including four in the liver and eight in the duodenopancreatic area, and four outside the abdomen, including two in the mediastinum. Six of the ten tumoral sites which were not correctly identified by somatostatin receptor scintigraphy were located in the duodenopancreatic area. However, in the 20 patients for whom conventional techniques failed to visualize any tumour in the duodenopancreatic area, somatostatin receptor scintigraphy was positive in ten (50%) whereas endoscopic ultrasonography was only positive in five (25%). In our patients with the Zollinger-Ellison syndrome, somatostatin receptor scintigraphy appeared to be a useful new addition to the battery of tests used for tumour detection.
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PMID:Somatostatin receptor scintigraphy in forty-eight patients with the Zollinger-Ellison syndrome. GRESZE: Groupe d'Etude du Syndrome de Zollinger-Ellison. 785 70

Historically, the interplay between basic research and clinical observation has been essential in the development of new therapies for peptic ulcer disease. That histamine is an important regulator of acid secretion emerged from basic research, followed by the clinical development and use of the H2-receptor antagonists. Basic research contributed again by defining the importance of H+/K(+)-ATPase in acid secretion, resulting in a new class of useful antisecretory agents. Basic studies also gave us prostaglandins (PG) as mucosal protective agents. As 'replacement' therapy, clinicians have found that PG are protective against non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulcer (GU). Physiologic studies established that somatostatin is a potent inhibitor of acid secretion, providing the stimulus for clinical studies in Zollinger-Ellison (ZE) Syndrome with a synthetic analog (octreotide). Work on isoforms of the parietal cell gastrin receptor has shown differences in the cytoplasmic domain for G protein coupling. This will aid in understanding how receptor changes and coupling to second messengers relate to the aetiopathogenesis of abnormal gastric secretion. Immune cells express mRNA for histamine, muscarinic and gastrin receptors, supporting the relevance of mucosal immunology in gastroenterology, especially in light of Helicobacter pylori-associated gastritis and ulcers. Lab research has revealed a potential role for basic fibroblast growth factor (bFGF), and another endogenous peptide BPC-15, in ulcer healing. The former substance may be responsible for the antiulcer efficacy of sucralfate. Intensive basic work on how H. pylori organisms attach to gastric cells and initiate inflammatory reactions in the mucosa will have unquestionable impact on improved therapy for peptic ulcer disease.
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PMID:Clinical relevance of basic research in peptic ulcer disease. 788 Oct 29

Among endocrine tumors occurring in the gastrointestinal tract, midgut argentaffin EC cell carcinoids, gastric argyrophil ECL cell carcinoids, duodenal gastrin cell tumors, and rectal trabecular L cell carcinoids (in order of decreasing frequency) are those occurring more frequently. Together, they account for more than 80% of such tumors. Duodenal somatostatin cell tumors, gangliocytic paragangliomas, and differentiated neuroendocrine carcinomas are also well-defined tumor entities. The carcinoid syndrome, either classical, with intermittent flushing, hypotension, and diarrhea, or atypical, with persistent histamine-type red flushing, bronchospasm, and no diarrhea, and Zollinger-Ellison syndrome, with severe peptide ulcer disease, are the only hyperfunctional syndromes consistently found in association with these tumors. The carcinoid syndrome occurs in about 10% of gastrointestinal carcinoids, usually in their advanced, metastatic stage. The Zollinger-Ellison syndrome occurs in association with about 40% of intestinal gastrin cell tumors, including small intramural growths. Tumor prognosis depends on the mode and site of presentation, histology, cell type(s), size, level of invasion, metastases (especially distant metastases), and associated clinical syndrome or background disease. Hormones, trophic factors, inherited genetic traits, somatic mutations, and some chronic inflammatory processes are pathogenetically important in a large proportion of cases.
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PMID:The pathology of the gastrointestinal endocrine system. 812 73

Somatostatin receptor scintigraphy (SRS) was performed in 14 patients (five men, nine women; mean age 51.5 [20-71] years) with Zollinger-Ellison syndrome (ZES), a gastrinoma proven in 7 and suspected on clinical or biochemical grounds in 7. The results were compared with those obtained by other methods (ultrasound, computed tomography, angiography). All 12 known tumour manifestations were demonstrated by SRS in seven patients with histologically confirmed gastrinoma. In four patients previously non-localized tumour was revealed by SRS, while in seven other patients the procedure led to modification of the treatment (primary tumour resection: n = 3, resection of metastases: n = 2, percutaneous radiation or chemoembolization: one each). These results suggest the following indications for SRS: (1) staging or re-staging in histologically proven gastrinoma and (2) search for primary tumour in clinically and biochemically suspected ZES.
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PMID:[Somatostatin receptor scintigraphy in the primary diagnosis and follow-up care of gastrinoma]. 813 15


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