Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We compared the maximal calcitonin secretion produced by pentagastrin, calcium, and glucagon for preoperative detection of medullary thyroid carcinoma in four subjects with normal or slightly increased plasma immunoreactive calcitonin (iCT) levels. In each case, pentagastrin administration produced higher peak iCT levels (5- to 36-fold increases over basal) than did calcium infusion (by 1.9- to 10.3-fold) and glucagon administration (by 3.6- to 27.4-fold). These preliminary studies suggest that pentagastrin is an effective agent for use in rapid stimulation tests designed to detectmedullary thyroid carcinoma in asymptomatic patients who have normal basal iCT concentrations.
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PMID:Stimulation tests for diagnosis of medullary thyroid carcinoma. 111 54

The gross, histomorphologic, cytochemical, and immunocytochemical findings in 16 dogs with medullary thyroid carcinoma were evaluated. Grossly, the neoplasms were encapsulated, firm, lobulated, and grey-white to tan. The typical histologic pattern was groups or sheets of round to polygonal cells with fibrovascular stroma, which was thickened and hyalinized in places. Variants of clear cell (two dogs), giant cell (one dog), and oxyphil cell (one dog) types were also seen. In all 16 dogs, Grimelius-stained sections of the neoplasms revealed intracytoplasmic silver granules; ten tumors contained amyloid and four contained mucin. Immunohistochemically, the neoplasms reacted to AE1/AE3 (n = 13), S-100 protein (n = 5), neuron specific enolase (n = 14), synaptophysin (n = 11), calcitonin (n = 16), somatostatin (n = 4), gastrin (n = 7), and serotonin (n = 6). Only one neoplasm was positive for vimentin. None of the neoplasms reacted to antibodies for neurofilaments, thyroglobulin, insulin, glucagon, or adrenocorticotrophic hormone. Eleven neoplasms contained multiple (two to four) peptides, in various combinations. It was concluded that in dogs, gross and histologic features can be used to distinguish medullary thyroid carcinoma from other thyroid malignancies. Cytochemical and immunocytochemical studies with neuron specific enolase, synaptophysin, and calcitonin can be used to establish the diagnosis of medullary thyroid carcinoma in dogs.
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PMID:Gross, histologic, cytochemical, and immunocytochemical study of medullary thyroid carcinoma in sixteen dogs. 190 46

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

Calcitonin secretion dynamics of a medullary thyroid carcinoma in tissue culture was studied by addition of calcium chloride (20 mM), magnesium chloride (20 mM), glucagon (6 x 10(-6) M), and pentagastrin (3 x 10(-6) M). After correction by protein content, calcium caused the greatest release of calcitonin to medium (264%), and glucagon the lowest (48%), in relation to control values. The direct action of glucagon on calcitonin secretion of medullary thyroid carcinoma was confirmed. This system may be also used for testing quimiotherapics acting upon the tumor.
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PMID:[Dynamics of calcitonin secretion in tissue culture of medullary thyroid carcinoma]. 281 86

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

Although the benign counterpart of medullary carcinoma of the thyroid has never been indicated in textbooks, we propose that C cell adenoma is a rare but distinct clinical entity. Two patients, a 43-year-old man and a 53-year-old woman, had similar thyroid tumors, both about 4 cm in diameter. The cut surfaces of the resected tumors were indistinguishable from a common microfollicular adenoma of the thyroid. Microscopically, the tumors were uniformly composed of fusiform cells without any follicle formation. Neither amyloid deposition nor calcification was found. Although some kind of C cell tumors were suggested, the exact nature was debatable. However, extremely high levels of calcitonin (1330 and 2065 pg/ml, respectively; normal level, less than 170 pg/ml) were found in the stored sera taken preoperatively. Serum levels of carcinoembryonic antigen (CEA) were normal in both patients. Immunohistochemically, the tumor tissues were positive for calcitonin and neuron-specific enolase but negative for CEA with a monoclonal anti-CEA antibody. No somatostatin, glucagon, or adrenocorticotropic hormone activity was found. It is highly probable that such tumors have not been closely studied and have been regarded as eccentric adenomas of the thyroid or simply as the so-called medullary carcinomas of the thyroid.
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PMID:C cell adenoma of the thyroid: a rare but distinct clinical entity. 319 51

A series of six ovarian strumal carcinoids was examined. The presence of thyroid follicular epithelium was conclusively proved by the presence of follicular cells immunohistochemically positive for thyroglobulin, and by the ultrastructural identification of non-neuroendocrine cells with features of thyroid epithelium lining the follicles. Progressive replacement of thyroid epithelial cells by carcinoid cells accounts for the predominance of neuroendocrine granule-containing cells and the scarcity of thyroid epithelial cells lining many of the follicles. A variety of neuroendocrine hormones and other immunoreactive substances was demonstrated within carcinoid cells, including somatostatin (five cases), chromogranin (five cases), serotonin (five cases), glucagon (four cases), insulin (two cases), and gastrin (one case). Only one case contained calcitonin-positive cells. None were carcinoembryonic antigen-positive or had amyloid deposits. The carcinoid element in five cases stained positively for prostatic acid phosphatase. While strumal carcinoid shares some features with medullary carcinoma of the thyroid gland, it has sufficient differences to warrant a separate designation.
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PMID:Strumal carcinoids of the ovary. An immunohistologic and ultrastructural study. 355 74

Medullary thyroid carcinoma (hMTC) cells were established from nine patients with MTC disease to initiate a new approach of adjuvant medical therapy in these patients. We measured calcitonin (CT) secretion, DNA synthesis, and cell proliferation in vitro and their response to various substances. Nerve growth factor (NGF) (0.01 to 10 micrograms/ml), glucagon (0.01 to 100 micrograms/ml), and isoproterenol (4 to 500 micrograms/ml) stimulated CT secretion and DNA synthesis in hMTC cells. Other substances, calcium (1.0 to 15 mmol), pentagastrin (1.0 to 50 mumol), dibutyryl-cyclic-adenosine-monophosphate (1.0 to 100 mumol), and phorbol ester TPA (1.0 to 100 nmol), stimulated CT secretion but not DNA synthesis. In addition, NGF enhanced cell proliferation of hMTC cells 2- to 3- fold and caused an increased sensitivity of these cells for chemotherapy in vitro. Thus 0.5 microgram/ml doxorubicin (half-maximal effective dose) induced a cell death rate of up to 32.8%, which was enhanced by preincubation with NGF to 68.1% (1.0 microgram/ml, NGF) and to 100% (10.0 micrograms/ml, NGF), respectively. Pulsative stimulation of APUD cell carcinomas with NGF may therefore improve the response rate of these tumors to chemotherapy, which would be of significant clinical importance for patients with residual postoperative MTC tissue.
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PMID:Nerve growth factor (NGF) sensitizes human medullary thyroid carcinoma (hMTC) cells for cytostatic therapy in vitro. 368 43

Twenty-seven cases of medullary carcinoma of the thyroid gland (MCT) were studied by light microscopy, immunocytochemistry, and electron microscopy. Immunoreactivity for neuron-specific enolase (NSE) and calcitonin was present in all tumors. The numbers of peptides and serotonin demonstrated in each case varied from one to eight. Bombesin was present in 18 of the 27 cases, serotonin in 15, leu-enkephalin in 8, somatostatin in 8, gastrin in 3, substance P in 1, vasoactive intestinal peptide (VIP) in 1, and ACTH in 1. Insulin and glucagon were not encountered in any of the tumors. Immunoreactivity for thyroglobulin was seen in five primary tumors as well as in one lymph node metastasis. The finding of concurrent production of calcitonin and thyroglobulin within the same tumor is enough to question the dogma of the separate origin of follicular cells and C-cells. We were unable to attach any clinical importance to the production of multiple peptides and/or amines.
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PMID:Medullary carcinoma of the thyroid gland: an immunocytochemical study. 390 54

Tissue cultures of four C-cell carcinomas (medullary thyroid carcinoma, MTC) were prepared to study the basal and stimulated calcitonin (CT) and carcinoembryonic antigen (CEA) release. Immunohistological staining of the explants for CT and CEA have been performed after various periods of culture. These MTC explants were able continuously to release CT and CEA for periods up to 157 days. The spontaneous CT and CEA release decreased sharply during the 1st week of culture, then remained nearly constant over the observation period. THE CEA/CT secretion ratio slightly declined during long-term culture; CEA release seems to drop earlier than CT production. CT and CEA could be detected in the same cells by immunocytochemical technique. The septal tissue consisting of dense connective tissue and amyloid produced by tumor cells seemed to increase during long-term culture. CT, but not CEA, was stimulated by pentagastrin (10(-5) M), glucagon (6 x 10 (-6) M), and dose related by calcium (2.5-20 mM) in vitro. The MTC explant organ long-term culture proved to be a useful model for studies of human CT and CEA secretion.
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PMID:Secretion of calcitonin and carcinoembryonic antigen in long-term organ culture of human medullary thyroid carcinoma: biochemical and immunocytochemical studies. 399 Jan 62


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