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)

The authors report a case of neuroendocrine carcinoma of the lower third of the esophagus. Immunohistochemical study revealed that most tumor cells expressed neuron specific enolase, chromogranin A, carcinoembryonic antigen and glucagon. They insist on the usefulness of this study on biopsies in order to guide therapeutic decision.
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PMID:[Neuroendocrine carcinoma of the esophagus. Case report with immunohistochemical study]. 129 57

The proglucagon gene is expressed in A cells of the pancreas and L cells of the large and small intestine. Transgenic mice expressing SV40 large T antigen under the control of proglucagon regulatory sequences develop neuroendocrine carcinoma of the large intestine. To determine the consequences of coexpression of SV40 large T antigen and proglucagon in different cell types, the levels of proglucagon mRNA transcripts and proglucagon-derived peptides were determined in tumor-bearing transgenic mice and in age-matched paired controls. Plasma levels of proglucagon-derived peptides (glicentin, oxyntomodulin, and glucagon, as determined by high pressure liquid chromatography and radioimmunoassay) were markedly elevated in association with tumor growth (p < 0.001). Northern blot analysis demonstrated that the increased concentration of proglucagon-derived peptides was associated with significant inhibition of the endogenous proglucagon gene in pancreas, and to a lesser extent, small intestine. Concomitantly, the concentrations of proglucagon-derived peptides fell to 1-10% of control values in pancreas (p < 0.001) and to 62% of control values in small intestine (p < 0.001). Analysis of proglucagon-derived peptides in mice of different ages demonstrated that tumor growth was associated with a switch in the post-translational processing of proglucagon. Compared with normal mouse intestine, tumors contained increased proportions of glucagon and glucagon-like peptide-1(7-37) relative to glicentin, oxyntomodulin, and glucagon-like peptide-1(1-37). The results of these studies provide evidence for humorally-mediated tissue-specific inhibition of proglucagon gene expression.
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PMID:Alterations in proglucagon processing and inhibition of proglucagon gene expression in transgenic mice which contain a chimeric proglucagon-SV40 T antigen gene. 132 10

Transgenic mice that express a glucagon gene-simian virus-40 large T-antigen (GLUTag) fusion gene develop neuroendocrine carcinoma of the large bowel. This glucagon-producing tumor was implanted sc and reproducibly formed tumors in nude mice. The transplanted GLUTag tumor expressed large amounts of proglucagon mRNA transcripts, and the levels of proglucagon mRNA transcripts remained constant during 2-8 weeks of tumor growth. The posttranslational processing of proglucagon in the transplantable tumor resembled that detected in the original transgenic tumor, with the liberation of glicentin, oxyntomodulin, glucagon, glucagon-like peptide (1-37) [GLP-1-(1-37)] and GLP-1-(7-37). Tumor-bearing mice demonstrated progressive elevations in the plasma levels of proglucagon-derived peptides. Elevated plasma levels of glucagon-like immunoreactive peptides and immunoreactive glucagon were associated with a marked reduction in the levels of pancreatic glucagon mRNA transcripts by 4 weeks, and after 8 weeks of tumor growth, the levels of glucagon mRNA transcripts in the pancreas were not detectable by Northern blot analysis. Synthesis of the proglucagon-derived peptides was also significantly suppressed at 4-8 weeks in the pancreas of tumor-bearing animals. Histological examination of the endocrine pancreas in mice carrying the GLUTag tumor for 6-8 weeks demonstrated a marked reduction in the number and size of the islets of Langerhans and a disproportionately greater decrease in the number of cells exhibiting glucagon immunoreactivity. By electron microscopy, the residual A-cells were small, compressed at the periphery of the islets, and had poorly developed cytoplasmic organelles. In contrast, no changes in mouse glucagon gene expression or islet morphology were detected in control animals without tumors or mice carrying a sc v-jun-induced fibrosarcoma. The suppression of pancreatic A-cell function and islet size in mice with elevated plasma levels of the proglucagon-derived peptides raises the possibility that a proglucagon-derived peptide may participate in a negative feedback loop, inhibiting expression of the glucagon gene in the A-cells of the endocrine pancreas.
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PMID:Inhibition of pancreatic glucagon gene expression in mice bearing a subcutaneous glucagon-producing GLUTag transplantable tumor. 149 97

From 1980 to 1987, 35 patients underwent exploratory surgery for carcinomas of the extrahepatic biliary tract (EBT). Samples from 28 of these tumors (15 gallbladder, 13 bile duct) were assessed by immunohistochemical analysis for exocrine and/or neuroendocrine differentiation. Seven patients were excluded from the study because of insufficient available specimen or loss to follow-up. Paraffin sections were immunostained for neuroendocrine differentiation markers: neuron-specific enolase (NSE), chromogranin-A, synaptophysin, serotonin, somatostatin, substance-P, and glucagon. Additional sections were also stained with monoclonal antibody A-80 that recognizes a glycoprotein related to exocrine differentiation. The tumors were reclassified on the basis of immunophenotyping data: (I) pure exocrine carcinoma (n = 8); (II) predominantly exocrine carcinoma with occasional neuroendocrine cells (n = 9); (III) mixed exocrine-neuroendocrine carcinoma (n = 4); (IV) pure neuroendocrine (n = 2); and (V) predominantly neuroendocrine with occasional exocrine cells (n = 5). Survival time among the two pure neuroendocrine (group IV) and five predominantly neuroendocrine carcinomas (group V) was significantly less than the survival time of patients from the other groups (2.6 +/- 2.2 months vs 13.5 +/- 12.3 months; p = 0.015). No difference was noted between groups in extent of disease, treatment rendered, or location of tumor (bile duct vs gallbladder). This study indicates that (1) the incidence of neuroendocrine differentiation in cancers of the EBT is higher than generally recognized, (2) carcinomas of the EBT may be phenotypically reclassified on the basis of immunohistochemical analysis, and (3) the presence of pure or predominant neuroendocrine differentiation in carcinomas of the EBT is associated with shorter survival time than carcinomas with pure or predominant exocrine differentiation (or mixed exocrine and neuroendocrine factors).
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PMID:Neuroendocrine differentiation and prognosis of extrahepatic biliary tract carcinomas. 171 46

High circulating levels of somatostatin (SRIF) were detected in a patient with a metastatic tumour after development of diabetic ketoacidosis (DKA). Fasting insulin and C-peptide levels were markedly suppressed, but plasma glucagon was not suppressed below normal. Progressive cachexia ensued; at autopsy a poorly differentiated non-small cell neuroendocrine carcinoma metastatic to liver was found. Small gallstones were noted. Electron microscopy of tumour tissue showed neurosecretory granules and tonofilament bundles. Immunohistochemical staining of tumour cells was diffusely positive for carcinoembryonic antigen, bombesin-like immunoreactivity, and calcitonin with focal immunoreactivity for SRIF, serotonin, neuron-specific enolase, chromogranin, and epithelial membrane antigen. Column chromatography of plasma and tumour extract revealed five or more peaks of material with SRIF-like immunoreactivity (SRIF-LI): predominantly SRIF-28 and intermediates in tumour extract, and SRIF-14 and an intermediate between SRIF-28 and SRIF-14 in plasma, DKA in this case of somatostatinoma syndrome may reflect differential effects of tumour production of larger molecular weight SRIF forms on insulin and glucagon secretion.
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PMID:Malignant somatostatinoma presenting with diabetic ketoacidosis. 282 97

Seventeen rectal neuroendocrine tumors ("Rectal Carcinoids") were studied by immunohistochemistry using antibodies directed against neuroendocrine markers: chromogranin A, neuron-specific enolase, synaptophysin, neuroendocrine peptides (ACTH, glicentin, glucagon, pancreatic polypeptide, somatostatin, vasoactive intestinal peptide) and antibody against serotonin. All patients with tumors measuring 1 cm or less had no specific symptoms and survived between fifteen months and eight years. Only one patient with a 6 cm poorly differentiated neuroendocrine carcinoma died less than one year after diagnosis. Only five out of seventeen tumors secreted serotonin. Most tumors were derived from L cell secreting glucagon, glicentin or pancreatic polypeptide.
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PMID:[Immunohistochemical study of 17 cases of rectal neuroendocrine tumors]. 876 75

Primary hepatic carcinoid and neuroendocrine carcinoma (NEC) are rare tumors. We experienced three carcinoids and two NEC originating in the liver during the past 25 years and attempted to elucidate the clinicopathological and immunohistochemical features of these tumors. The patients had no endocrine symptoms despite two of them having elevated plasma serotonin. Three of the five patients died of the tumor after operation with an average survival time of 20.6 months. All tumors were large (up to 26 cm in diameter), four of them solitary and one multinodular, and were not associated with liver cirrhosis. The carcinoid tumors showed insular, trabecular or glandular arrangement of argyrophilic cells, whereas in the NEC this histological pattern was distorted. Immunohistochemically the tumors showed expression of chromogranin A (all cases), chromogranin B (three cases), pancreastatin and chromostatin (four cases, respectively), prohormone convertase PC3 (three cases), carcinoembryonic antigen (CEA) and CA19-9 (two cases), cytokeratin 56 kDa (three cases), 160 kDa neurofilament (two cases) and neuron-specific enolase (two cases). Serotonin and glucagon were sporadically detected in two tumors. The most useful marker to confirm the diagnosis was chromogranin A, which was cleaved to pancreastatin and chromostatin in the tumor tissue, and was more reliable than other markers of neuroendocrine differentiation.
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PMID:Primary hepatic carcinoid and neuroendocrine carcinoma: clinicopathological and immunohistochemical study of five cases. 1036 51

A nine-year-old neutered female crossbred Bernese mountain dog was diagnosed with superficial necrolytic dermatitis and a glucagon-producing islet cell tumour. Laboratory findings included hyperglucagonaemia and hypoaminoacidaemia. The dog was euthanased because of progression of the disease, and necropsy revealed liver metastases of a neuroendocrine carcinoma with immunohistochemical expression of glucagon and somatostatin. This report represents a case of canine glucagonoma syndrome; the previously reported cases in dogs are also briefly described.
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PMID:Glucagon-producing neuroendocrine tumour associated with hypoaminoacidaemia and skin lesions. 1102 26

Small cell carcinomas of the uterine cervix are rare tumors with an aggressive behavior. Although these tumors can exhibit neuroendocrine differentiation, the criteria for neuroendocrine differentiation are subjective and not well defined. In this study, the authors tentatively defined small cell neuroendocrine carcinoma (SCNEC) as a tumor composed of small cells with at least two of the following: argyrophilic cytoplasm, chromogranin A immunoreactivity, and synaptophysin immunoreactivity. We found 10 cases fulfilling these requirements. Five of the 10 tumors were composed mainly of small ("oat") cells and 5 of mainly larger "intermediate" cells. The majority of both subtypes showed an insular pattern. Three of the 10 SCNECs were pure, whereas the other seven were mixed with adenocarcinoma and/or squamous cell carcinoma or cervical intraepithelial neoplasia. In addition to the definitional markers noted earlier, the tumors were immunoreactive for serotonin (6 cases), somatostatin, gastrin, glucagon, and pancreatic polypeptide. No tumors were immunoreactive for cytokeratin 20. Human papillomavirus (HPV)-18 was detected in all of the pure tumors and both the SCNEC and adenocarcinomatous components in four of the mixed tumors. No other types of HPV were detected. The tumors showed a relatively low frequency of loss of heterozygosity for representative tumor suppressor gene sites; p53 mutations were found in only one case.
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PMID:Small cell neuroendocrine carcinomas of the uterine cervix: a histological, immunohistochemical, and molecular genetic study. 1538 6

Neuroendocrine tumors of the lung are carcinomas characterized by different impact on the patients' prognosis, ranging from relatively indolent, low- to intermediate-grade neoplasms with longer life expectation (i.e., typical and atypical carcinoids) to very aggressive and poorly differentiated neoplasms with dismal prognosis (i.e., large cell neuroendocrine carcinoma and small cell lung cancer). The standard treatment of typical or atypical carcinoids is the complete surgical resection, whereas the role of radio-chemotherapy in a multimodality treatment or for palliation remains controversial. Conversely, high-grade neuroendocrine carcinomas are in primis treated by aggressive combination chemotherapy, deserving surgical resection for uncommon low-stage tumors. Since evidence has been accumulated that neuroendocrine tumors of the lung are supplied with a wide array of peptide receptors detectable on cell membranes by immunohistochemical methods, innovative strategies for diagnosis and radiometabolic therapy have been devised to target these molecules for the correct clinical management of the patients. In this paper, the structural and functional aspects and the clinical applications of the detection of several peptide receptors in pulmonary neuroendocrine tumors will be reviewed, including somatostatin receptors, vasoactive intestinal peptide/pituitary adenylate cyclase activating peptide family receptors, cholecystokinin /gastrin receptors, bombesin/gastrin releasing peptide receptors, neurotensin receptors, substance P receptors, neuroepeptide Y receptors, calcitonin/calcitonin gene-related peptide receptors, atrial natriuretic peptide receptors, glucagon-like-peptide-1 receptors, oxytocin receptors and endothelin receptors. Only a detailed knowledge of the peptide receptor distribution in these tumor types, especially in uncommon neoplasms such as atypical carcinoids and large cell neuroendocrine carcinomas, is pivotal for planning the most adequate interventions for the patients' diagnosis and therapy.
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PMID:Peptide receptors in neuroendocrine tumors of the lung as potential tools for radionuclide diagnosis and therapy. 1704 25


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