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)

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome linked to mutations in the MEN1 gene, which encodes a 610-amino-acid nuclear protein termed menin. Because of the lack of a suitable detection protocol, the in situ expression pattern of menin in human tissues remains to be determined. In this study, we have developed an antimenin monoclonal antibody and an indirect immunofluorescence/laser-scanning microscopy protocol for analyzing menin expression in frozen tissue sections. Because neuroendocrine pancreatic tumors represent a key feature of MEN1, we focused this study on nontumoral pancreas and a small panel of neuroendocrine pancreatic tumors. Results showed that menin was readily detected in nontumoral exocrine cells. In contrast, most islet cells expressing insulin, glucagon, or somatostatin showed considerably weaker levels of menin expression; however, a subpopulation of pancreatic polypeptide-positive cells exhibited a signal comparable with that detected in adjacent exocrine cells. Sporadic endocrine tumors showed variable levels of menin expression, whereas a MEN1-/- gastrinoma scored negative. This report thus provides the first description of the expression pattern of menin in human pancreas in situ and lays the groundwork for further studies of other tissues and tumors.
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PMID:In situ analysis of human menin in normal and neoplastic pancreatic tissues: evidence for differential expression in exocrine and endocrine cells. 1291 85

The role of surgery in the management of patients with sporadic (not part of multiple endocrine neoplasia type 1) Zollinger-Ellison syndrome (ZES) is controversial. In this setting, 60-90% of gastrinomas are malignant and medical therapy can control the gastric acid hypersecretion in virtually every patient. Therefore, the progression of tumor is the major determinant of survival. Surgery will cure approximately one-third of patients with sporadic ZES. It will decrease the development of liver metastases and may improve survival. Somatostatin receptor scintigraphy is the best preoperative localization study. Its results are as good as all other imaging studies combined. Operative techniques should always include duodenotomy (opening the duodenum) and meticulous dissection of lymph nodes in the gastrinoma triangle, because duodenal primary tumors are often missed and lymph node primary tumors or metastases are common. Postoperative evaluation should include secretin test because it is the most sensitive method to document cure and detect tumor recurrence.
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PMID:Current surgical management of Zollinger-Ellison syndrome (ZES) in patients without multiple endocrine neoplasia-type 1 (MEN1). 1294 85

The somatostatin analogue octreotide was effective in controlling systemic effects related to multiple liver metastases from a gastrinoma. A 61-year-old man underwent distal gastrectomy for gastrinoma in the duodenum, because a curative resection was not feasible due to metastases found in paraaortic lymph nodes during operation. Multiple liver metastases, associated with an increase in serum gastrin concentration, were found by magnetic resonance imaging 16 months after the operation. Although chemotherapy with dimethyltrizenoimidazole carboxamide was not effective, subcutaneous administration of octreotide was effective in controlling the growth of the liver metastases and in stabilizing serum gastrin. The patient now receives subcutaneous injections of octreotide, at 200 microg a day, twice a week, as an outpatient.
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PMID:Octreotide in control of multiple liver metastases from gastrinoma. 1456 38

Over the last decade somatostatin receptor scintigraphy using various derivatives of long-acting somatostatin analogues has gained its place in the management of pancreatic islet-cell tumours. Scintigraphy is based on the high-affinity binding of such somatostatin analogues to receptors over-expressed by these tumour types. Following the introduction of (111)In-DTPA-D-Phe(1)-octreotide, clinical studies with radiolabelled DOTA-Tyr(3)-octreotide and DOTA-Tyr(3)-octreotate derivatives have shown considerable improvement of imaging results with increased tumour uptake. One of the newer developments, (68)Ga-labelled DOTA-Tyr(3)-octreotide, has shown promising results in patients with pancreatic islet-cell tumours, based on the high-affinity binding to the somatostatin receptor subtype 2 in combination with positron emission tomography (PET) technology. Other peptides--such as ligands for the gastrin/CCK2 receptors or vasoactive intestinal peptide (VIP)--have also been studied for imaging pancreatic cell tumours. Whereas small-sized gastrinoma, somatostatinoma, glucagonoma, carcinoid and VIPoma are frequently detected by somatostatin receptor scintigraphy, insulinoma may escape detection due to reduced receptor expression. Following peptide receptor scintigraphy, a change in patient management is reported in up to 30% of patients. When labelled with (90)Y or (177)Lu, some somatostatin analogues have been applied to patients in advanced stages of the disease. Despite positive response data in 50% of patients, long-term results and survival rates are lacking.
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PMID:Nuclear medicine in the detection and management of pancreatic islet-cell tumours. 1576 96

Only relatively recently has there been an increased clinical recognition and characterization of the heterogeneous group of rare gastroenteropancreatic neuroendocrine neoplasms. Most have endocrine function and exhibit varying degrees of malignancy. This review summarizes the derivation of these tumors and the advances in their diagnosis and treatment over the past decade and a half. They are varied in their biological behavior and clinical courses and, depending on their cell type, can produce different hormones causing distinct clinical endocrine syndromes (insulinoma [hypoglycemia], gastrinoma [Zollinger-Ellison syndrome (ZES)], vasoactive intestinal peptideoma [VIPoma], watery diarrhea, hypokalemia-achlorhydria [WDHA], glucagonoma [glucagonoma syndrome], and so forth). In addition to surgery for cure or palliation (by excision and a variety of other cytoreductive techniques), they each are treated with anti-hormonal agents or drugs targeted to each tumor's specific product or its effects. The majority have benefited from the gut hormone-inhibiting action of somatostatin analogs. Because of their usual slow rate of growth it is recommended that, even when they are advanced and incurable, unlike in patients with common and more malignant cancers, patients with neuroendocrine tumors often can be palliated and appear to survive longer when managed with an active approach using sequential multimodality treatment. Advances in these various therapies are reviewed and the beneficial emergence of global self-help patient support groups is noted.
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PMID:Enteroendocrine tumors other than carcinoid: a review of clinically significant advances. 1588 58

Gastrinomas of the stomach are extremely rare endocrine tumors producing Zollinger-Ellison syndrome. We report here the case of a patient with gastrinoma of the stomach who presented regional and hepatic metastases at the time of diagnosis. The endocrine tumor was discovered incidentally 8 yr after the onset of symptoms related to peptic ulcer, which responded to medical treatment with a proton pump inhibitor. Surgery did not cure the patient, as demonstrated by provocative tests showing serum gastrin responses indicative of residual disease. A long-term treatment with the somatostatin analog lanreotide induced a biochemical response and was associated with a substantially stable disease.
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PMID:Gastrinoma of the stomach: a case report. 1611 Jan 23

Zollinger-Ellison syndrome (ZES) is characterised by peptic ulcers of the upper gastrointestinal tract failing to heal despite maximal medical therapy, diarrhoea and marked gastric acid hypersecretion associated with a gastrin-secreting tumour (gastrinoma). ZES might be associated with multiple endocrine neoplasia type 1. The main diagnostic features are hypergastrinemia and acid hypersecretion. When these parameters give borderline results, provocation test (with secretin or calcium) may be required. To identify the localisation of gastrinoma several imaging techniques have been proposed. Somatostatin receptor scintigraphy is capable to localise the tumour in 80% of the cases and to identify it even in anatomic sites other than pancreas and duodenum. Endoscopic ultrasonography has a sensitivity as high as 79-93% and a specificity of 93%. The 2 main principal therapeutic strategies are to control both the gastric acid hypersecretion and the growth of the neoplasia. Proton pump inhibitors (PPIs) are the drugs of choice for patients with ZES. Furthermore, safety of PPIs in the maintenance therapy has been proven both in short- and in long-term studies. The best surgical treatment is excision of gastrinoma before metastatic spread has occurred. Somatostatin-analogues can reduce both gastric acid hypersecretion and serum gastrin levels. Moreover, they have an antiproliferative effect. Chemotherapy, interferon and embolisation are indicated in rapidly evolving tumours or in cases in which the tumoral symptoms cannot be treated by other approaches.
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PMID:Zollinger-Ellison syndrome in 2006: concepts from a clinical point of view. 1663 30

In summary, neuroendocrine tumors of the pancreas comprise a unique and relatively rare group of tumors, of which gastrinoma and insulinoma are the most common types. Insulinomas tend to be small, solitary and benign, with surgical resection curable in most cases. The remainder of the neuroendocrine tumors are usually large, and unlikely to be cured with surgery; their slow-growing nature, however, mandates aggressive surgical therapy; even in cases where metastatic disease is present. Somatostatin analogs such as octreotide, are used to control the symptoms of hormone secretion; they are generally less effective in patients with insulinoma than in those with the other neuroendocrine tumors. Streptozocin, 5-fluorouracil, and doxorubicin are the most widely used chemotherapeutic agents in metastatic neuroendocrine tumors; their efficacy is limited, and significant side effects limit their use. Finally, liver transplantation in very select patients may prolong survival and alleviate debilitating symptoms.
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PMID:Neuroendocrine tumors of the pancreas, excluding gastrinoma. 1688 94

Several circulating or urinary tumour markers can be used for the diagnosis and follow-up of functioning and clinically non-functioning neuroendocrine tumours of the pancreatic islet cells and intestinal tract. Among the specific tumour markers are serotonin and its metabolites--e.g. 5-hydroxyindoleacetic acid (5-HIAA)--in carcinoid tumours and the carcinoid syndrome, insulin and its precursors or breakdown products in insulinoma, and gastrin in gastrinoma. Plasma vasointestinal polypeptide (VIP) determinations have been used in the diagnosis of VIPoma, plasma glucagon for glucagonoma, and serum somatostatin for somatostatinoma. Among the tumour-non-specific markers are: chromogranins, neuron-specific enolase (NSE), alpha-subunits of the glycoprotein hormones, catecholamines, pancreatic polypeptide (PP), ghrelin and adrenomedullin.
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PMID:Biochemistry of neuroendocrine tumours. 1738 64

Gastric carcinoid tumors are uncommon, but their percentage among all gastric malignancies has increased to 1.8%. Although they are most often discovered incidentally during endoscopy, gastric carcinoids can present with abdominal pain, bleeding, or symptoms related to the secretion of bioactive substances, most commonly histamine. Gastric carcinoids originate from the foregut and are derived from histamine-containing enterochromaffin-like (ECL) cells. Type I gastric carcinoid, the most common, exhibits slow growth and benign behavior. It occurs within the setting of chronic atrophic gastritis with achlorhydria-induced hypergastrinemia. Gastrin acts directly on ECL cells to induce hyperplasia, dysplasia, and, eventually, neoplasia. Type II gastric carcinoid, the least common type, occurs in patients with gastrinoma-associated multiple endocrine neoplasia syndrome-type 1 (MEN-1). The overall survival is related more to the underlying MEN-1 syndrome than to the gastric carcinoid. Rodents readily develop gastric carcinoid tumors in response to hypergastrinemia. However, in humans, other factors in addition to hypergastrinemia, such as pernicious anemia or MEN-1, must be present, implying that a genetic predisposition is necessary for the development of these tumors. Type III or sporadic gastric carcinoids exhibit a more malignant behavior, with overall 5-year survival rates of less than 50% and normal serum gastrin concentrations. Treatment of all types of gastric carcinoids is predicated upon accurate classification and staging. Radiolabeled somatostatin analogues are superior to conventional radiologic imaging techniques in detecting both primary and metastatic lesions. Treatment of choice for localized disease is excision, either endoscopically or surgically. Antrectomy, by eliminating the trophic effect of gastrin, can be useful for select type I carcinoids. Long-acting somatostatin analogues are excellent palliative agents.
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PMID:Treatment of gastric carcinoids. 1739 27


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