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)

Rat prosomatostatin was isolated from a somatostatin-producing cell line and was partially microsequenced. This indicated the amino terminal structure of cellular prosomatostatin and implied a 92-amino acid sequence for the somatostatin precursor. Based on the structure for cellular prosomatostatin, a peptide was synthesized and used to develop a radioimmunoassay directed toward the amino terminal portion of prosomatostatin. This assay has revealed two peptides containing the amino-terminal portion of prosomatostatin in a somatostatin-secreting CA-77 rat medullary thyroid carcinoma cell line. These two peptides - MW 4000 and 8000 daltons - lack somatostatin immunoreactivity. Thus, processing of prosomatostatin occurs both at the amino and carboxyl regions. These results open the way for elucidation of the structure, function and metabolism of non-somatostatin peptides derived from the amino terminus of prosomatostatin.
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PMID:Identification of cellular prosomatostatin and nonsomatostatin peptides derived from its amino terminus. 614 49

Clinical and laboratory data, histologic, electron microscopic and immunocytochemical findings of the tumors of eight patients suffering from Cushing's syndrome and of one patient with hypercalcemia are described. The unlabeled antibody enzyme method was used for the detection of insulin, glucagon, somatostatin, pancreatic polypeptide, corticotropin, beta-lipotropin, calcitonin, parathyroid hormone, and gastrin. Ectopic Cushing's syndrome was caused by pancreatic endocrine tumors, medullary thyroid carcinoma, a bronchial, a gastric and a thymic carcinoid, and a carcinoid of the mediastinum. Hypercalcemia in one patient was related to a pancreatic endocrine tumor. After surgery the clinical symptoms disappeared in two patients, but persisted or relapsed in five patients. ACTH-immunoreactivity could be demonstrated in six of eight tumors; calcitonin-immunoreactivity was found in the tumor of the patient suffering from hypercalcemia. ACTH-immunoreactivity could be localized to secretory granules by immunoelectron microscopy, and the presence of ACTH and beta-LPH in the same tumor cells could be shown in one pancreatic tumor. A combination of production of orthotopic and ectopic hormones was found in one, and secretion of two ectopic hormones was detected in another pancreatic endocrine tumor.
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PMID:Ectopic hormone production by endocrine tumors: localization of hormones at the cellular level by immunocytochemistry. 627 90

A rat medullary thyroid carcinoma cell line, CA-77, has been established as a model system for investigating calcitonin biosynthesis and secretion. Growth of this cell line in serum-free defined medium provided suitable conditions for studying steroid hormone effects on the production of calcitonin and related peptides. After exposure for 5 days to a variety of steroids, only dexamethasone and corticosterone increased cellular content of calcitonin and a second secretory peptide (CCAP) derived from the same mRNA translation product as calcitonin. Glucocorticoids had no effect on cellular somatostatin, another secretory product of these cells. Increasing doses of dexamethasone progressively elevated cellular calcitonin and CCAP, with a maximal effect at 10(-8) M; 10(-9) M and lower doses were ineffective. On a molar basis, corticosterone was approximately 50-fold less potent than the synthetic glucocorticoid. An increase in cellular calcitonin content was observed only after 48 h of glucocorticoid treatment; a maximum increase (13-fold) occurred after 7 days. Glucocorticoids also increased basal calcitonin secretion. Similar effects were observed for cellular and secreted CCAP. Withdrawal of dexamethasone after 4 days of treatment lowered cellular calcitonin toward the level of control cultures. Dexamethasone pretreatment potentiated the acute secretory response to calcium for both calcitonin and CCAP, while no such enhancement was noted for calcium stimulation of somatostatin secretion. We conclude that the glucocorticoids specifically stimulate the production and secretion of calcitonin and CCAP, two secretory peptides derived from preprocalcitonin.
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PMID:Glucocorticoids stimulate the production of preprocalcitonin-derived secretory peptides by a rat medullary thyroid carcinoma cell line. 631 19

The serum gastrin response to a standard test meal was evaluated in patients with familial medullary thyroid carcinoma (MTC) and in normal subjects. Patients with MTC and elevated plasma calcitonin levels had a lower gastrin response to the test meal than did normal persons or MTC patients who had normal calcitonin levels postthyroidectomy. There was no significant difference between the mean gastrin response of the normal group and that of the MTC patients with normal calcitonin levels. The serum gastrin response was studied before and after thyroidectomy in four patients. In all four, the post-operative response was greater than the preoperative one . We conclude that patients with MTC may have reduced gastrin responses to a test meal. This effect may be related to circulating calcitonin, somatostatin, or other factors related to familial MTC.
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PMID:Gastrin Responses to a test meal in patients with familial medullary thyroid carcinoma. 706 88

An autopsied patient with medullary carcinoma of the thyroid and ectopic ACTH syndrome is reported. A microadenoma of pancreatic islet coexisted in this case, which is assumed to be of D cell origin. Immunohistochemical study revealed decreased number of pituitary ACTH cells. Some of them showed Crooke's degeneration. Hormone assay study of tumor tissue and plasma disclosed abnormal ACTH, beta-MSH as well as calcitonin. Somatostatin and Substance P were also demonstrated in tissue. Histologically the tumor showed solid alveolar pattern with a minor part consisting of small cell variant and this histologic variation is discussed.
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PMID:Medullary carcinoma of the thyroid with ectopic ACTH syndrome. 713 94

Somatostatin (SRIF) immunoreactivity has been frequently reported in tumor tissues of cell types, belonging to the APUD system, including medullary thyroid carcinoma (MTC). However, the value of SRIF as a plasma tumor marker for MTC is controversial. We have measured SRIF plasma levels in 35 patients with different stages of MTC to evaluate the use of SRIF as a plasma tumor marker compared to the current "gold standard" calcitonin (CT). The median SRIF value in healthy controls was 36.5 pg/mL, the upper limit of normal was defined at the controls. The median value was 28 pg/mL (p = 0.37, Mann-Whitney U test). Five patients in the control group and three in the MTC group had SRIF levels that exceed the 95th percentile. SRIF and CT levels correlated only weakly (0.38), as determined by the Spearman rank order correlation test. Pentagastrin stimulation led to a diagnostic increase in SRIF levels in only one of five MTC patients. During selective venous catheterization, diagnostic gradients for CT, allowing tumor localization, could be demonstrated, whereas measurement of SRIF levels did not aid in tumor detection. Although SRIF immunostaining may be valuable as an additional marker in the histochemical diagnosis of MTC, SRIF has no value as a plasma tumor marker in the diagnosis of this disease.
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PMID:Evaluation of somatostatin as a plasma tumor marker in medullary thyroid carcinoma. 748 70

Requisites for preoperative and intraoperative tumor localization with [111In]diethylenetriaminepentaacetic acid-D-[Phe1]-octreotide scanning were explored in 23 patients with endocrine tumors (15 carcinoids, 4 insulinomas, and single cases of gastrinoma, medullary thyroid carcinoma, aldosteronoma, and paraganglioma). The patients were subjected to Octreoscan single photon emission computed tomographic examination prior to surgery and well counter investigation of nuclide uptake in tumors and normal tissues sampled at surgery. Somatostatin receptor-positive tumors demonstrated efficient nuclide accumulation with mean tumor:blood radioactivity ratios of 180-370 (for carcinoids and insulinoma), compared with tissue:blood ratios of 302 for spleen, 42 for liver, and < 10-15 in other normal tissues (pancreas, small intestine, and mesenteric fat). Inefficient preoperative visualization of lesions was related to inconspicuous size, as for primary intestinal carcinoids, tiny liver metastases, and a single small insulinoma. High background activity, pronounced tumor fibrosis, and meager accumulation of tracer also interfered with visualization. Tumor deposits in organs with low background activity (such as carcinoid mesenteric metastases and endocrine pancreatic tumors) were generally most readily detected. Intraoperative investigations with hand-held gamma detector probes were disturbed by obvious high background activity. These investigations revealed two preoperatively unrecognized primary intestinal carcinoids, which, however, were both palpable during surgery. These studies, therefore, had little impact on the surgical strategy.
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PMID:Human biodistribution of [111In]diethylenetriaminepentaacetic acid-(DTPA)-D-[Phe1]-octreotide and peroperative detection of endocrine tumors. 749 48

The regulation of cholecystokinin and somatostatin expression by vitamin D and cyclic AMP in the rat medullary thyroid carcinoma cell line CA-77 was investigated. Treatment with 100 nmol/l vitamin D did not affect cholecystokinin mRNA and peptide concentrations significantly; somatostatin mRNA level increased 6 times and the somatostatin peptide concentration increased 2-fold after 5 days of drug treatment. Under the same experimental conditions cyclic AMP increased cholecystokinin mRNA level 4.5 times and the cellular cholecystokinin-peptide concentration 2-fold; somatostatin mRNA and peptide concentrations were not significantly changed. Cyclic AMP stimulated peptide secretion from the cells were not affected by vitamin D, but cyclic AMP mediated increase in CCK peptide concentration was significantly inhibited by vitamin D (p < 0.05).
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PMID:Vitamin D3 effects on basal and cAMP modulated expression of cholecystokinin and somatostatin genes in a rat medullary thyroid carcinoma cell line [CA-77]. 756 12

The increased understanding of the neuroendocrine tumors at a cellular and molecular level has led to the development of new radiopharmaceuticals for imaging. Two of the imaging agents include 131I metaiodobenzylguanidine (131I-MIBG) and 111In-DTPA-D-Phe1-octreotide (111In-pentetreotide) each having specific localization in certain neuroendocrine tumors. The selective uptake of these radiopharmaceuticals by the tumor cells has generated interest in potential use for targeted radiotherapy for neuroendocrine tumors. 131I-MIBG has been used to treat patients with pheochromocytoma, neuroblastoma, carcinoid tumors, medullary thyroid carcinoma, and paragangliomas. The tumor responses have been variable with the most encouraging results being in patients with pheochromocytoma. The dose-limiting toxicity has been thrombocytopenia or granulocytopenia. 111In-pentetreotide has been used as therapy in only a few patients and has resulted in objective evidence of tumor responses. A therapeutic agent using a somatostatin analogue will most likely require radiolabeling with a beta- or possibly an alpha-emitting radionuclide to achieve significant and durable tumor responses.
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PMID:Therapy of neuroendocrine tumors with radiolabeled MIBG and somatostatin analogues. 757 46

Medullary thyroid carcinoma is an uncommon cancer of the thyroid gland. It comprises a neuroendocrine tumor of the calcitonin secreting cells. Its level of aggressiveness lies between that of well-differentiated and anaplastic thyroid malignancies. We have undertaken a retrospective study of 18 patients with medullary thyroid carcinoma to evaluate various parameters for their prognostic value. We looked at epidemiologic factors such as stage, age at onset, sex and the heredity of the disease. In addition various immunohistochemical stains were looked at including Leu-M1, calcitonin, thyroglobulin, somatostatin, carcinoembryonic antigen, neuron specific enolase and BRST-1. Finally, DNA ploidy was determined using the flow cytometer. Stage, age at onset, DNA ploidy and staining for BRST-1 were found to be significant factors in determining outcome of this disease.
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PMID:Medullary thyroid carcinoma: prognostic factors. 769 Apr 9


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