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)

Twenty medullary carcinomas of the thyroid gland were examined for the presence of immunoreactive calcitonin, thyroglobulin, glucagon, keratin, gastrin/CCK, carcinoembryonic antibody (CEA), insulin, serotonin, adreno-corticotropic hormone (ACTH), prostatic acid phosphatase, and somatostatin using the immunoperoxidase peroxidase-antiperoxidase technique. In addition, they were stained with mucicarmine, alcian blue/periodic acid-Schiff (PAS), Grimelius, Congo red, crystal violet, and Fontana-Masson stains. Calcitonin-immunoreactive cells were absent in one tumor and present in 19 tumors (95%). Thyroglobulin was present in seven tumors (35%). Twenty tumors contained CEA-immunoreactive cells (100%). Fourteen cases were immunoreactive to serotonin (70%) and 12 were positive for somatostatin (60%). Glucagon- and gastrin/CCK-immunoreactive cells were found in two cases each (10%). Four tumors (20%) contained ACTH-immunoreactive cells and three cases (15%) were positive for prostatic acid phosphatase. Five cases (25%) contained keratin-immunoreactive cells. One case was immunoreactive to insulin (5%). Grimelius-positive cells were present in 19 of the cases (95%). Mucin-containing cells were present in 65% of the cases. The validity of the immunocytochemical localizations was tested by specific absorption of each antibody with the corresponding antigen. The demonstration of immunoreactivity for multiple antigens in each of the 20 cases suggests that the origin of medullary thyroid carcinomas is from a neuroendocrine cell potentially capable of producing numerous hormone substances. In addition, as the neoplastic cells in 35% of the tumors contained hormonal substances as well as thyroglobulin, it is suggested that papillary or follicular tumors mixed with a neuroendocrine component exist more commonly than previously suspected. Finally, psammoma bodies might be present in pure medullary carcinoma of the thyroid gland.
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PMID:Medullary carcinoma of the thyroid gland. Clinical, pathological, and immunohistochemical features with review of the literature. 241 97

A somatostatin analog (SMS 201-995) was used to treat symptomatic patients with a residual tumor burden of gastrinoma or medullary thyroid carcinoma and pathologic elevations of circulating marker peptides associated with these neuroendocrine tumors. Possible inhibitory effects of the analog on marker peptides, patients' symptoms, or tumor progression were studied in a dose-response protocol and during several months of self-injection of SMS 201-995. Both patients reported remarkable relief of secretory diarrhea and other symptoms, and serum gastrin was successfully suppressed by increasing doses of the analog. However, no effect was seen in reduction of hypercalcitoninemia. Morphologic imaging of residual tumor showed no progression of medullary thyroid carcinoma during treatment and, in the case of hepatic gastrinoma metastases, remarkable tumor regression was confirmed. No toxicity or glucose intolerance was experienced. Somatostatin analog shows promise for palliative management of endocrinologic symptoms due to neuroendocrine tumors, and an inhibitory effect can be measured in some but not all peptide markers. Further evidence of its negative trophic effect on tumor blood flow may suggest an antineoplastic potential, as well as palliative use of this new treatment.
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PMID:Somatostatin analog: effects on hypergastrinemia and hypercalcitoninemia. 243 92

Parafollicular (PF) cells have been found to be a good model system for the study of serotonergic cellular mechanisms relevant to neurons. PF cells are derived from the same region of the neural crest that gives rise to the neurons of the gut and are capable of extending neurofilament-bearing neuritic processes. PF cells also synthesize 5-hydroxytryptamine (5-HT) and costore 5-HT in the same vesicles as the specific 5-HT-binding protein, 45 kDa SBP. A hypothesis has been advanced that PF cells and enteric neurons share a common developmental precursor. The present investigation was undertaken in order to determine whether a human medullary thyroid carcinoma (MTC) cell line, which is derived from PF cells, sufficiently mimics PF cells that it can be substituted for them in investigations of serotonergic cellular biology. In contrast to PF cells, MTC cells can be propagated in vitro to provide adequate amounts of material for biochemical studies. MTC cells were found to contain neuropeptides, including calcitonin, calcitonin gene-related peptide, and somatostatin, which have also been reported to be present in PF cells and enteric neurons. MTC cells also were observed to store endogenous 5-HT, to be able to synthesize 3H-5-HT from 3H-L-tryptophan, and to take up 3H-5-HT from the ambient medium by a carrier-mediated mechanism very similar to that of serotonergic neurons. In addition, the longterm accumulation of 3H-5-HT in MTC cells was antagonized by reserpine, suggesting that the cells contain 5-HT storage vesicles that, like the synaptic vesicles of serotonergic neurons, are characterized by a reserpine-sensitive transporter of biogenic amines. MTC cells also contain type A, but not type B, monoamine oxidase. Finally, MTC cells were found to contain both 45 and 56 kDa SBP. MTC cells thus retain a great many of the properties of PF cells, and, like PF cells, they are serotonergic cells with characteristics similar to serotonergic neurons. Substantial differences were found in the content of immunoreactive 5-HT and neuropeptides in individual MTC cells. Moreover, the release of newly synthesized 5-HT to the medium exceeded the ability of the cells to store the amine. Studies of the ultrastructure of the MTC cells revealed a limited and highly variable number of secretory granules, probably accounting for their limited 5-HT storage capacity and for the heterogeneity of immunostaining with antisera to 5-HT or neuropeptides.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Human medullary thyroid carcinoma: characterization of the serotonergic and neuronal properties of a neurectodermally derived cell line. 253 40

The authors evaluated the presence of somatostatin (SRIF) in the plasma and in the tumor tissue of a total of 22 patients with medullary thyroid cancer (MTC) and studied the effect of exogenous SRIF administration on basal and pentagastrin (PG)-stimulated plasma calcitonin (CT) and carcinoembryonic antigen (CEA) levels. Mean plasma SRIF concentrations were significantly higher than those found in normal controls, with five of 15 patients having plasma SRIF levels above the mean + 2 SD of normal controls. High immunoreactive SRIF concentrations were found in the extract of three tumor tissues but not in one follicular thyroid cancer or in one toxic diffuse goiter. By immunoperoxidase staining seven of 11 (63.6%) primary MTC and five of 13 (38.5%) metastases expressed SRIF antigen in a low number of cells and with a weak degree of staining. As expected, CT was expressed in almost 100% of the cases with positivity in most of the cells and strong degree of staining. Patients with positive SRIF staining in the primary tumor had longer survival than SRIF negative patients. Infusion of synthetic SRIF (11 micrograms/minute/45 minutes) produced a significant reduction of plasma CT (but not CEA) levels in 12 of the 15 patients submitted to this test. Maximal percent decrease of plasma CT ranged from 10.8% to 72.7% of the basal value and was usually observed between 30 and 45 minutes from the beginning of the infusion. When infused together with the injection of PG, SRIF was able to significantly (P less than 0.05) inhibit the PG-induced CT release in five of six patients tested. These results demonstrate the following: SRIF is present in a few cells of many primary MTC and less frequently in their metastases; tentatively, the expression of SRIF antigen in the tumor seems to be associated with longer survival; increased SRIF concentrations are found in the plasma of some patients with metastatic involvement; and treatment with exogenous SRIF reduces the basal and PG-induced CT (but not CEA) release from the tumor.
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PMID:Somatostatin in medullary thyroid cancer. In vitro and in vivo studies. 256 68

A retrospective study of 224 patients with medullary thyroid carcinoma (MTC) diagnosed between 1963 and 1988 was performed to 1) establish the diagnosis of MTC in early childhood, 2) establish the role of prophylactic regional lymphadenectomy in patients with MTC, 3) study the effect of chemotherapy on MTC patients with metastatic disease, 4) study the effect of somatostatin analog 201-995 (Sandoz Pharmaceuticals) on the frequency of diarrhea in MTC, and 5) locate the common region(s) of gene deletion on chromosome 1 and examine the loss of heterozygosity on chromosome 10 in tumors. Our data indicated that a progressive rise of serum calcitonin in early childhood (rather than the expected fall with age seen in normal subjects) is diagnostic of MTC. No differences in clinical course of prognosis were observed between patients with MTC localized to the thyroid who had prophylactic neck node dissection and those who did not. Conventional chemotherapy had no significant benefit in the treatment of patients with metastatic disease. The somatostatin analog was found to be an effective drug in the treatment of diarrhea associated with MTC. Allelic losses were frequently found in MTCs and pheochromocytomas, and the loss of DNA sequences in these tumors appeared to involve the distal third of the short arm of chromosome 1, with a common breakpoint at 1p32.
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PMID:Diagnosis, management, and pathogenetic studies in medullary thyroid carcinoma syndrome. 257 46

Recent studies have suggested that somatostatin could reduce calcitonin plasma levels (CT) in normal subjects and in medullary thyroid carcinoma (MTC). The aim of this study was to examine the usefulness of the somatostatin analog, sandostatine (SMS 201.995) in MTC with elevated residual CT levels post-thyroidectomy with or without metastases. 18 patients (17-64 years, 12 men and 8 women) with CT greater than 850 pg/ml (N less than 150 pg/ml) and with metastases in 12 cases, were studied. MTC was sporadic in 11 cases, familial in 4 cases and of undefined form in 3. Initial posology was 300 micrograms/d of sandostatin (3 injections/day). It was then increased by 300 micrograms/d every 9 day till a maximum of 1500 micrograms/d. Treatment duration was 37 days in 11 cases and 60 days in 7 cases. Plasma CT and carcinoembryonic antigen levels (CEA) were measured before treatment and at the end of each dosage plateau. Morphologic evaluation of metastases was done at 0, 30, 60 days. 7/18 patients were reevaluated 2 to 8 months after with drawal of sandostatine. Treatment was well tolerated. Flushes improved in 4 out of 5 cases but diarrhea in only 2 out of 9 patients. Sandostatine was without any effect on plasma CEA. Heterogenous responses were observed for plasma CT levels (CT decreases greater than 20% in 8/18 patients when 900 to 1500 micrograms/day were administered). Patients were subdivised into 3 groups according to CEA levels and presence or absence of metastases. Group A (n = 9) had elevated CEA levels (greater than 10 mg/ml) and metastases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of subcutaneous administration of sandostatine (SMS 201.995) in 18 cases of thyroid medullary cancer]. 263 43

A rare case is reported of melanin-producing medullary thyroid carcinoma in a 62-year-old man. Intraoperative imprints of the thyroid tumor revealed numerous detached tumor cells containing large amounts of brown pigment. The Fontana-Masson argentaffin reaction with bleach confirmed that those granules were melanin. Histologically, the tumor was composed of two different components--a medullary area with hyalinized stroma and a follicular area. Melanin was scattered in both areas. The tumor cells in both areas were immunoreactive to carcinoembryonic antigen, calcitonin, gastrin-releasing peptide, somatostatin, met.-enkephalin, neuron-specific enolase, chromogranin and neurofilaments, and negative for thyroglobulin and S-100 protein. The histologic diagnosis was melanin-producing medullary thyroid carcinoma with glandular differentiation. Although various kinds of peptides and amines have been reported to be produced in medullary thyroid carcinoma, melanin production is quite rare; this appears to be only the third reported case.
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PMID:Melanin-producing medullary thyroid carcinoma with glandular differentiation. 264 44

Our current knowledge of the processes regulating somatostatin biosynthesis is still scarce. Approaches used for the direct investigation of somatostatin biosynthesis in different tissues include 1) analysis of incorporation of labeled amino acids into somatostatin-like immunoreactivity (SLI), 2) cell-free translation of mRNA isolated from SLI producing tissues and 3) analysis of mRNA coding for somatostatin by cDNA blot hybridization. Amino acid incorporation into SLI has been studied in a variety of systems, including anglerfish and rat pancreas, frog retina, rat dorsal root ganglia, cerebral cortex and hypothalamus. We have studied the neuronal biosynthesis of somatostatin using monolayer cultures of neonatal rat hypothalamic cells. Following pulse labeling with [3H]phenylalanine, the cellular extracts contained material that bound specifically to an immobilized anti-somatostatin antibody. Analysis of the bound label by gel chromatography and HPLC provided evidence for the presence of labeled somatostatin-14 (S-14), somatostatin-28 (S-28) and a precursor molecule of Mr 15,000 (15 K SLI). Pulse-chase experiments demonstrated a transfer of label from 15K SLI to material corresponding to S-28 and S-14. Using cloned cDNAs complementary to somatostatin mRNA, the presence of somatostatin mRNA has been demonstrated in anglerfish pancreas and intestine, rat hypothalamus and antrum, as well as in a rat medullary thyroid carcinoma and a rat pancreatic cell line. We have recently studied the developmental regulation of somatostatin gene expression in the rat brain and stomach. Messenger RNA hybridizing specifically to a rat somatostatin cDNA probe was already clearly detectable in tissue extracts derived from brains of one week old rat fetuses. A marked increase of somatostatin mRNA occurred between day 14 and day 21 of embryonic life. By contrast, in tissue extracts derived from stomach, somatostatin mRNA remained undetectable until shortly before birth. These marked differences in the tissue specific regulation of somatostatin gene expression during ontogenesis may reflect basic differences in the developmental regulation of somatostatin gene expression in neural vs. nonneural tissues or may be related to the onset of functional activity in the organs studied.
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PMID:Approaches to the study of somatostatin biosynthesis. 286 49

We have established a system, the CA77 rat medullary thyroid carcinoma cell line, for studying the products of somatostatin (SS) gene expression. Based on the amino acid sequence of proSS, we developed a RIA for the amino terminus of proSS (proSS-NTP) and demonstrated in acidic cell extracts two major proSS-NTP-containing species of 8000 and 4000 daltons. Studies were then performed on species secreted into culture medium. Serial dilutions of culture medium showed tracer displacement curves parallel to serial dilutions of synthetic proSS-NTP standard. Analysis by gel filtration chromatography of 24-h culture medium showed the major proSS-NTP-containing species to have an estimated mol wt of 8000 daltons. No 4000-dalton species was observed. The acute effects of calcium and glucagon, known secretagogues of SS, on secretion of immunoreactive (i) proSS-NTP were investigated in 3-h experiments. Basal (0.5 mM calcium) secretory rates (mean +/- SE) of iproSS-NTP and iSS were 1.29 +/- 0.36 and 7.38 +/- 1.51 ng/mg acid-extractable protein, respectively. High calcium (3 mM) stimulated iproSS-NTP and iSS secretion 302 +/- 100% and 363 +/- 105%, respectively. High calcium plus 10(-6) M glucagon also stimulated secretion of iproSS-NTP and iSS in a coordinate fashion. Analyses by gel filtration chromatography of 3-h culture medium revealed that high calcium markedly increased the 8000-dalton proSS-NTP-containing species. No 4000-dalton species was observed. The absence of 4000-dalton proSS-NTP species in 24-h culture medium, the lack of degradation of 4000-dalton proSS-NTP (recovered from CA77 cell extracts) added to tissue culture medium, and the selective secretion of the 8000-dalton proSS-NTP species under both basal and stimulated conditions coordinate with the secretion of SS indicate that the 4000-dalton proSS-NTP-containing species is not secreted.
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PMID:Nonsomatostatin secretory peptide(s) derived from prosomatostatin's amino terminus in a rat medullary thyroid carcinoma cell line. 286 50

Somatostatin (SRIF, SRIF-14) is a known product of the normal and malignant parafollicular cell of the thyroid. In this report we characterize SRIF production by the TT cells, a line of transformed calcitonin-producing cells derived from a human medullary thyroid carcinoma. The cells were found to contain (5-12 ng/10(6) cells) and secrete (3-10 ng/10(6) cells X 48 h) immunoreactive SRIF. Molecular sieve chromatography of cell extracts under denaturing conditions showed a major peak with a mol wt slightly larger than 12,700, probably representing pro-SRIF and a second peak which coeluted with SRIF; in one gel chromatogram a very small peak was also noted which coeluted with SRIF-28, but represented less than 0.4% of the total immunoreactive SRIF. Short term secretion of calcitonin and SRIF was stimulated by calcium in vitro (0.5-4 mM) in a dose-related manner. mRNA isolated from the TT cells hybridized to a specific bovine fetal pancreatic SRIF DNA (BFPS-2); there was no hybridization to identical amounts of mRNA from the atT-20/D16, 3T3, or RINC5F cell lines. In vitro translation of the TT cell mRNA followed by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the product revealed a single protein band of approximately 13,000 daltons. It was completely abolished when the immunoprecipitation was performed in the presence of excess unlabeled SRIF. Northern transfer of TT cell cytoplasmic RNA and hybridization with FBPS-2 cDNA showed a single hybridizing band with an apparent size of approximately 750 nucleotides. Our observations demonstrate the production of SRIF by a continuous line of human medullary thyroid carcinoma cells and provide a model for studying the biosynthesis and secretion of SRIF in the parafollicular cell.
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PMID:Somatostatin production by a human medullary thyroid carcinoma cell line. 286 83


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