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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three pancreatic beta-cell lines have been established from insulinomas derived from transgenic mice carrying a hybrid insulin-promoted simian virus 40 tumor antigen gene. The beta tumor cell (beta TC) lines maintain the features of differentiated beta cells for about 50 passages in culture. The cells produce both proinsulin I and II and efficiently process each into mature insulin, in a manner comparable to normal beta cells in isolated islets. Electron microscopy reveals typical beta-cell type secretory granules, in which insulin is stored. Insulin secretion is inducible up to 30-fold by glucose, although with a lower threshold for maximal stimulation than that for normal beta cells. beta TC lines can be repeatedly derived from primary beta-cell tumors that heritably arise in the transgenic mice. Thus, targeted expression of an oncogene with a cell-specific regulatory element can be used both to immortalize a rare cell type and to provide a selection for the maintenance of its differentiated phenotype.
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PMID:Beta-cell lines derived from transgenic mice expressing a hybrid insulin gene-oncogene. 284 53

The role of cytoplasmic activator of adenylate cyclase in rat lung metabolism was investigated. Mouse adrenal tumor (MAT) cells undergo differentiation in response to choleratoxin which acts through cyclic AMP. The activator of adenylate cyclase from rat lung also produced cyclic AMP in a disrupted MAT cell preparation. However, unlike choleratoxin, it did not induce MAT cell differentiation in whole cells. These results suggest impermeability of MAT cells, and possibly other cells, to the activator. Thus, means of altering activator activity in lung cytoplasm were sought, and changes in activator activity were related to lung glycogen. Adrenalectomy (ADX) in rats led to a reduction in activator activity that was accompanied by an elevation in lung glycogen. Dexamethasone treatment of adrenalectomized rats reversed both of these effects. Streptozotocin-induced diabetes in rats elevated activator activity and lowered lung glycogen. Insulin treatment of the diabetic rats restored activator activity to the normal control values. Preweaning of rats on day 16 instead of day 22 increased activator activity on the 19th day over the controls and there was a concomitant decrease in lung glycogen. Feeding the separated pups with homogenized milk restored glycogen and activator activity to the control values. These results indicate that activator activity in rat lung cytoplasm was dependent on the circulating levels of cortisol and insulin, and that there appeared to be an inverse relationship between activator activity and glycogen level in rat lungs.
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PMID:Relationship between the cytoplasmic activator of adenylate cyclase and glycogen metabolism in rat lung. 285 15

Surgical fragments of healthy and tumor-bearing pancreas from a patient with pancreatic tumor were studied by electron or light microscopy, histochemistry, and immunocytochemistry (human insulin, glucagon, somatostatin, gastrin, and bovine pancreatic polypeptide). Histological results were compared to those obtained by radioimmunoassay, both in tumor and serum. The tumor was identified as a glucagonoma because reactions for Grimelius' silver impregnation and immunoreaction with an antiserum against glucagon were positive and because a very high level of glucagon in the tumor was observed. Insulin, somatostatin, and gastrin levels remained normal, both in tumor and serum, but the glucagon level was normal in serum. Associated with this silent glucagonoma, an uncommon nesidioblastosis was also diagnosed with many A cells irregularly mixed with acinar cells, isolated or clustered in small groups. Acinar "intermediate" cells of "A" type were also observed. Such associative histopathological processes evoked possible development of an endocrine tumor from nesidioblastic-like tissue. Its embryogenic origin remained uncertain.
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PMID:Silent human pancreatic glucagonoma and "A" nesidioblastosis. 285 84

Using several tumor cell lines (HC-32, C-Hc4 and MHT-1), the anti-proliferating action of cis-dichlorodiamine platinum (cis-platin) was investigated in relation to the transferrin receptors (Tf-R) expressed on the surface of these cell lines. The number of Tf-R determined by 131I-transferrin binding assay was the most in HC-32, the least in C-Hc 4 and intermediate in MHT-1. Cis-platin was found to bind stoichiometrically to transferrin and to produce more marked inhibition of 3H-thymidine uptake in the presence of apo-transferrin, suggesting that cis-platin.transferrin complex was transferred into the cells through Tf-R. Cis-platin itself increased the binding sites of transferrin. Insulin, known to cause redistribution of Tf-R to the cell surface, potentiated the inhibition of 3H-thymidine uptake induced by cis-platin and apotransferrin in the concentrations less than 50 nM. Furthermore, insulin was found to increase the binding sites of transferrin in Hc-32 in the concentrations less than 5 nM. These facts support that cis-platin was effectively transferred into the cells through Tf-R, when apotransferrin coexisted with cis-platin. Some [Ca2+]0 and protein kinase C (PK-C) modulators affected Tf-R turnover in these cell lines. These results suggested the possibility that a combination treatment of cis-platin.transferrin complex with insulin or [Ca2+]0 and/or PK-C modulators may not only enhance the antiproliferating effect of cis-platin, but also reduce the dose of cis-platin.
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PMID:Experimental studies on the treatment of hepatocellular carcinoma with cis-platin.transferrin complex. 285 16

A long-acting somatostatin analog, SMS 201-995, is now available to treat the hormonal manifestations of islet cell tumors. We report its use in a patient with a metastatic glucagonoma refractory to conventional therapy. This patient, who was severely disabled by the rash of necrolytic migratory erythema and brittle diabetes mellitus, allowed us to evaluate the therapeutic efficacy of SMS 201-995 and to gain insight into the origin of the rash. SMS 201-995 was administered subcutaneously (.05 mg twice a day). The rash improved markedly within 48 hours and was completely resolved within 1 week of treatment. Insulin requirements decreased from 90 U/day to zero during the first week of treatment. Corresponding to improvement in clinical symptoms circulating glucagon levels showed a marked decrease. There was no substantial change in plasma or urinary levels of zinc or in plasma amino acid levels. When SMS 201-995 was stopped, the rash recurred within 36 hours and it improved within 48 hours of readministration. The rash and diabetes have remained well controlled during 8 months of therapy but no change in tumor size has been seen on CT scan. The rapid changes in the rash related to the administration of SMS 201-995 indicate that the pathogenesis of necrolytic migratory erythema is probably due to circulating hyperglucagonemia or some other hormonal substance produced by the tumor.
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PMID:Use of a somatostatin analog (SMS 201-995) in the glucagonoma syndrome. 287

Thirty-one primary canine pancreatic endocrine tumors and their metastases were studied histologically and immunohistochemically for the presence of insulin, glucagon, somatostatin, pancreatic polypeptide (PP), gastrin, and adrenocorticotrophic hormone (ACTH). Tumors were also evaluated for the presence of amyloid. The cytoarchitectural pattern of 25 of 31 primary tumors was predominantly solid, whereas three tumors were mostly glandular, two were unclassified, and one had a gyriform pattern. Cells with insulin immunoreactivity were found in 30 of 31 tumors and were found in all cases in which there was clinical evidence of inappropriate insulin secretion. Insulin was the only hormone demonstrable in three of the 30 tumors, but cells immunoreactive for other hormones were also present in various combinations in most tumors [i.e., glucagon (13 of 30), somatostatin (17 of 30), PP (25 of 30), and gastrin (2 of 30)]. One tumor contained only cells with glucagon and PP immunoreactivity. Amyloid was found in ten of 31 primary tumors but was not detected in metastases. Cells with insulin immunoreactivity were the only cell type consistently present in tumors containing amyloid. Amyloid deposits did not immunoreact with any of the antisera. Seventeen of 31 dogs had metastasis of the pancreatic endocrine tumor to regional lymph nodes, liver, or both. All metastases available for study (15 of 17) contained cells with insulin immunoreactivity and some contained cells with PP or somatostatin immunoreactivity. No statistically significant (P greater than 0.05) differences in tendency to metastasize were found when pancreatic endocrine tumors were compared by region of origin, cytoarchitectural pattern, presence of amyloid, or by number of hormones contained within the tumor.
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PMID:Canine pancreatic endocrine tumors: immunohistochemical analysis of hormone content and amyloid. 288 54

Incubation of chicken embryo fibroblasts with mitogenic concentrations of insulin for 24 hr or with the tumor promoter phorbol 12-myristate 13-acetate for 6 hr stimulated lactate release and 3-O-methylglucose uptake. Insulin also increased the Vmax of 6-phosphofructo-1-kinase (ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11). Both agents increased the concentration of fructose 2,6-bisphosphate and the activity of 6-phosphofructo-2-kinase (EC 2.7.1.-), the enzyme that catalyzes the synthesis of this stimulator of 6-phosphofructo-1-kinase. These changes provide an explanation for the stimulation of glycolysis by insulin and phorbol esters. In contrast to the situation in rat liver, fructose 2,6-bisphosphate concentration did not decrease after cyclic AMP treatment. Incubation of cells with phorbol ester analogues or with glycerol derivatives that are known to stimulate, or to bind to, protein kinase C did increase the concentration of fructose 2,6-bisphosphate, suggesting that the stimulation of 6-phosphofructo-2-kinase by phorbol 12-myristate 13-acetate is mediated by protein kinase C.
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PMID:Phorbol 12-myristate 13-acetate and insulin increase the concentration of fructose 2,6-bisphosphate and stimulate glycolysis in chicken embryo fibroblasts. 293 20

Histologic, immunofluorescence and ultrastructural studies were performed in 17 cases of pancreatic carcinomas induced by the BK virus in Syrian hamsters, a unique model of experimentally induced malignant islet cell tumors. The tumors were composed of small, poorly differentiated cells mostly arranged in a trabecular structure. By immunofluorescence all four islet cell types were found in the tumors, though with different frequency. Insulin cells were present in 16 cases, glucagon cells in 11, somatostatin cells in 7, PP cells in 6. Thirteen tumors contained more than one cell type. Insulin cells were the most frequent cell type in 13 cases, and glucagon cells predominated in 1 case. Insulin-containing cells usually occupied a central position within tumor-cell aggregates, while the other cell types were mostly located in a peripheral position, a distribution reminiscent of that seen in normal islets. Gastrin and calcitonin immunoreactivities were not observed. Immunoreactive cells were more abundant in tumors with trabecular structure. Argyrophil cells revealed by the Grimelius method often exceeded the cumulative number of immunoreactive cells in the same tumor, which suggests that there were additional cell types. Multiple cell types were also found in liver metastases. Ultrastructurally most neoplastic cells were poorly granulated. The occurrence of many damaged cells suggests hormone leakage, which may account, at least in part, for the deregulated hormone release from the tumors.
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PMID:Histologic, immunofluorescence, and ultrastructural study of malignant islet-cell tumors of the pancreas induced in hamsters by BK human papovavirus. 298 71

A case of simultaneous presentation of a small-cell carcinoma involving the ovary and the uterine endometrium is reported. We consider the endometrium as the primary localization of the tumor. The epithelial origin and neuroendocrine differentiation were confirmed by electron microscopy. Tumor cells were attached by small desmosomes, and in the cytoplasm typically neurosecretory granules measuring 100-200 nm were found. Immunohistochemically, no content of polypeptide hormones (ACTH, Calcitonin, Gastrin, Glucagon, Insulin, Somatostatin and VIP) were encountered. The tumor stained strongly for neuronspecific enolase. The histogenetic possibilities are shortly presented.
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PMID:Simultaneous presentation of a small-cell carcinoma involving the ovary and the uterine endometrium. 298 80

Adrenocortical carcinoma tissue removed from a mildly hirsute 16-year-old girl was cultured in order to assess steroidogenesis and responsiveness of the cells to adrenocorticotropic hormone (ACTH), human chorionic gonadotropin (HCG), and insulin. The cells in culture produced large amounts of androstenedione and testosterone; however, production of cortisol, which was initially high, decreased with time. No aldosterone, estrone, or estradiol was produced in vitro. Both monolayer cells maintained for 6 weeks and organ culture explants maintained for over 3 days responded to ACTH (10(-7) M) with increased production of androgens (testosterone, androstenedione, dehydroepiandrosterone) but decreased production of cortisol as measured by radioimmunoassay of steroids in the culture media. Concomitant with decreased cortisol production was the enhanced formation of 11-deoxycortisol in cells exposed to ACTH, suggesting impaired 11 beta-hydroxylation. Tissue exposed to HCG (10(-7) M) in organ culture showed an increase in androgen production over control levels, but no significant effect of HCG on glucocorticoid production was found. Tumor cells differed in their androgen response to ACTH and HCG, with enhanced adrenal androgens in the presence of ACTH and more gonadal-type androgens after exposure to HCG. Insulin exposure had no effect on production of either androgen or glucocorticoid by tumor tissue in organ culture. Thus, this adrenocortical carcinoma showed marked androgen production in culture which was enhanced in different ways by ACTH and HCG. 11 beta-Hydroxylation was impaired with time in culture. No specific effect of insulin on steroidogenesis was noted.
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PMID:Effects of adrenocorticotropic hormone, human chorionic gonadotropin, and insulin on steroid production by human adrenocortical carcinoma cells in culture. 299 Jun 78


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