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

Avian sarcoma virus (ASV) induces sarcomas in animals and transforms fibroblasts to a neoplastic state in cell culture. A single viral gene (src) is responsible for both the induction and maintenance of neoplastic transformation. Recent work has identified a protein with a molecular weight of 60,000 daltons that is apparently encoded in src and may be the effector molecule for the gene (Brugge and Erikson, 1977; Purchio et al, 1978). The putative product of src can be immunoprecipitated by antisera obtained from rabbits bearing tumors induced by ASV. We have used this approach to isolate the protein to characterize further its genetic origins and possible function. Our rabbit tumor antisera precipitated a protein with a molecular weight of 60,000 daltons; according to serological, biochemical and genetic criteria, this protein is encoded in src. We found that this protein is phosphorylated and therefore denoted it pp60. Phosphorylation of pp60 could be accomplished in vitro with extracts of ASV-infected cells. A temperature-sensitive conditional mutation in src had no demonstrable effect on either the production or stability of pp60 in the infected cell, but phosphorylation of the protein was temperature-sensitive. Since the mutant src is not expressed at the restrictive temperature, our findings raise the possibility that phosphorylation of pp60 is required for its function as the putative effector of src. Immunoprecipitates prepared with extracts of ASV-infected cells and the rabbit tumor antisera contained a protein kinase activity that catalyzed phosphorylation of the heavy chains of immunoglobulin molecules, using either ATP or GTP as phosphate donor. The kinase activity immunoprecipitated in parallel with pp60 was obtained only from cells that contained a functioning product of src and could not be precipitated with antisera directed against structural proteins of ASV. A temperature-sensitive conditional mutation in src caused the kinase activity to be thermally inactivated in vitro far more rapidly than the activity from cells infected with wild-type virus. We conclude that both the protein kinase and pp60 are encoded in src, and that the enzymatic activity may be an intrinsic property of pp60. Phosphorylation of pp60 in cellular extracts was inhibited by calcium ion, whereas the immunoprecipitable kinase activity was not, suggesting that the kinase responsible for pp60 phosphorylation may be distinct from that encoded in src. Collett and Erikson (1978) have also identified a protein kinase activity associated with pp60. These findings raise the possibility that phosphorylation of specific cellular targets might account for transformation of the host cell by src.
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PMID:Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein. 21 42

A calcium infusion (4 mg Ca++/kg/hr) significantly increased plasma insulin levels and reduced blood glucose in 4 patients with insulin-secreting pancreatic islet cell tumors. These parameters were not altered by a similar infusion of calcium in normal volunteers, 2 patients with alimentary hypoglycemia, and 2 with functional hypoglycemia. No difference in response was observed between patients with benign and malignant beta-cell tumors. Infusion of diazoxide (600 mg) with calcium blocked the stimulation of the latter on insulin secretion. The results indicate the usefulness of calcium infusion in the diagnosis of insulin-secreting tumor.
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PMID:Insulin release in response to calcium in the diagnosis of insulinoma. 21 87

Prostaglandin E concentrations were measured in a patiet with breast carcinoma, hypercalcemia, undetectable parathyroid hormone (PTH) and no evidence of bone metastases. Catheterization of the drainage bed of her tumor documented production of E series prostaglandins. Treatment with the largest recommended doses of indomethacin for 10 days failed to lower her plasma prostaglandin E (PGE) concentrations or to correct the hypercalcemia, but it normalized urinary excretion of PGE. Subsequent chemotherapy reduced prostaglandin concentrations toward normal values concomitant with a reduction of clinically estimated tumor burden. During this period of time, serum calcium concentrations had no consistent relationship to the plasma PGE levels. We suggest that PGE merely reflected the tumor burden of this patient and did not directly contribute to the genesis of her hypercalcemia. The pertinent literature relating PGE and hypercalcemia is reviewed.
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PMID:Prostaglandin E and hypercalcemia in breast carcinoma: only a tumor marker? A need for perspective. 21 52

The in vivo and in vitro effects of the dopamine precursor L-dopa on basal and stimulated calcitonin release from medullary thyroid carcinoma have been studied. In six studies of five patients, including 7- to 8-h control and test periods, oral L-dopa depressed basal calcitonin secretion by an average of 35%; the peak effects occurred within 30 min of drug administration and lasted for as long as 4 h. In seven of eight patients with medullary thyroid carcinoma (three infused with calcium and five with pentagastrin), L-dopa inhibited to varying degrees peak levels of stimulated calcitonin release and total calcitonin secretion; basal calcitonin levels, where directly tested, also again generally fell after L-dopa by an average of 50%. In a short term organ culture system using medullary thyroid carcinoma tissues, calcitonin secretion into the medium was linear with time for 2 h and could be stimulated by dibutyryl cAMP and pentagastrin. L-Dopa, in concentrations from 0.5--3.0 mM, inhibited basal calcitonin secretion (ranging from 25--55%). Addition of the L-dopa decarboxylase inhibitor, alpha-methyldopa, abolished the inhibitory effects of L-dopa. Another L-dopa decarboxylase inhibitor, carbidopa, stimulated calcitonin secretion in vitro; this effect may be independent of the L-dopa decarboxylase-inhibiting properties of this drug since alpha-methyldopa alone did not stimulate calcitonin secretion. It is concluded that the amine precursor L-dopa inhibits calcitonin release in patients with medullary thyroid carcinoma; the in vitro studies suggest that a portion of this effect may involve direct metabolism of L-dopa to dopamine in the tumor tissue itself. The importance of considering the uptake of amine precursors and the subsequent metabolism of these compounds as a modulating site for peptide hormone release from peripheral endocrine tissues is stressed.
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PMID:The effects of L-dopa on in vitro and in vivo calcitonin release from medullary thyroid carcinoma. 21 91

The Ca2+ content of glial tumor (C6) cells was reduced approximately 5-fold by repeated treatment with media containing ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA) without loss of cellular viability. The ability of the cells to accumulate cAMP in response to beta-adrenergic agonists was reduced 60 to 70% following Ca2+ depletion. Ca2+ did not affect the apparent KACT for norepinephrine, nor did it change the concentration of propranolol required to produce 50% inhibition of the maximal norepinephrine response. Phentolamine did not alter the Ca2+ dependence of the response. The binding of dihydroalprenolol by intact C6 cells was not influenced by Ca2+. Furthermore, pretreatment with norepinephrine did not affect the Ca2+ dependence of cAMP accumulation. The effects of Ca2+, therefore, appeared to be exerted on components of the adenylate cyclase system other than the catecholamine receptor. Micromolar free Ca2+ concentration in the extracellular medium were sufficient to restore a maximal norepinephrine response to Ca2+-depeleted cells. The effect of Ca2+ on cAMP accumulation in response to hormone was immediate and was rapidly reversible upon the addition of EGTA in excess of the cation. Cells in media containing Ca2+ exhibited a characteristic biphasic time course of cAMP accumulation; with Ca2+-depleted cells cAMP was accumulated more slowly and the subsequent decline in cAMP content was also reduced. Verapamil, an inhibitor of plasmalemmal Ca2+ influx, decreased the Ca2+-dependent component of the cAMP accumulation when added prior to the cation. The effect of Ca2+ on cAMP accumulation was reduced more extensively by pretreatment of cells at 45 degrees C under Ca2+-depleted (80% loss) than under Ca2+-restored (30% loss) conditions. Trifluoperazine at micromolar concentrations decreased the Ca2+-dependent increment in accumulation of cAMP in Ca2+-restored cells. This inhibition was not overcome by increasing concentrations of norepinephrine or of extracellular Ca2+.
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PMID:Calcium dependence of hormone-stimulated cAMP accumulation in intact glial tumor cells. 22 32

Tumor tissues obtained from two patients with the ectopic ACTH syndrome caused by medullary carcinoma of the thyroid and malignant epithelial thymoma were dispersed by tryptic digestion and mechanical agitation. Using the isolated cells, the effects of various agents on ACTH secretion and intracellular cAMP concentrations were studied. Addition of rat median eminence extract significantly stimulated ACTH secretion and increased levels of intracellular cAMP in both cell preparations, and a dose-response relationship appeared to exist between the dose of rat median eminence extract added and either ACTH secretion or intracellular cAMP formation in the thymic tumor cells. High concentrations of calcium also produced a marked ACTH secretion in both cases. In the thymic tumor cells, norepinephrine, serotonin, and TRH were found to be effective in increasing ACTH secretion and intracellular cAMP levels, whereas biogenic amines, hypothalamic hormones, and gastrointestinal hormones did not affect hormone secretion in the thyroid tumor cells. These results suggest that a corticortropin-releasing factor-like substance(s), as yet unspecified, may play some role in stimulating ectopic ACTH secretion by certain tumors, that both intracellular cAMP and Ca++ may be involved in ectopic hormone secretion, and that the inappropriate hormonal secretory responses of some tumors to a variety of stimuli might be mediated by altered membrane receptors of the neoplastic cells.
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PMID:Effect of hypothalamic extract and other factors on release of adrenocorticotropin from and adenosine 3',5'-monophosphate levels in dispersed nonpituitary tumor cells. 22 71

Calcium gluconate (10 mg Ca(++)/kg) was administered intravenously over a 2-hour period to 16 adult patients who were evaluated for hypoglycemia. In nine of ten patients with benign or malignant insulinomas (eight proven at operation, and two with positive chemical tests and angiographic localization awaiting operation), significant hypoglycemia and hyperinsulinemia occurred within 60 to 90 minutes after the start of the calcium infusion. Serum proinsulin and Cpeptide concentrations increased at the time of the calciuminduced hyperinsulinemia in several patients in whom these parameters were studied. The one individual who did not respond to the calcium infusion was found to have a benign insulinoma. His basal glucose/insulin ratio of 0.64 was the lowest of the insulinoma group and thus his failure to respond to calcium may indicate that his tumor was secreting maximally at the time of the infusion. Following successful removal of the insulinoma, calcium infusion did not result in changes in serum glucose or insulin concentrations (tested in five patients). In contrast, neither a patient with pathologically documented islet cell hyperplasia, five others with reactive, fupctional or drug-induced hypoglycemia, nor four healthy volunteers showed any changes in circulating glucose or insulin levels while receiving calcium intravenously. Calcium infusion is a safe, rapid and effective provocative test for the diagnosis of insulin-secreting, islet cell tumors of the pancreas.
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PMID:Calcium infusion: a new provocative test for insulinomas. 22 13

Calcium, in partnership with cyclic AMP, controls the proliferation of non-tumorigenic cells in vitro and in vivo. While it does not seem to be involved in the proliferative activation of cells such as hepatocytes (in vivo) or small lymphocytes (in vitro), it does control two later stages of prereplicative (G1) development. It must be one of the very many regulatory and permissive factors affecting early prereplicative development, because severe calcium deprivation reversibly arrests some types of cell early in the G1 phase of their growth-division cycle in vitro. However, calcium more specifically and much more often regulates a later (mid or late G1) stage of prereplicative development. Thus, regardless of its severity or the type of cell, calcium deprivation in vitro or in vivo reversibly stops proliferative development at that part of the G1 phase in which the cellular cyclic AMP content transiently rises and the synthesis of the four deoxyribonucleotides begins. The evidence points to calcium and the cyclic AMP surge being co-generators of the signal committing the cell to DNA synthesis. The evidence is best explained so far by the cyclic AMP surge causing a surge of calcium ions which combine with molecules of the multi-purpose, calcium-dependent, regulator protein calmodulin (CDR) somewhere between the cell surface and the cytosol. The resulting Ca-calmodulin complexes then stimulate many different (and possibly membrane-associated) enzymes such as protein kinases, one of which produces the DNA-synthetic initiator. Calcium has little or no influence on the proliferation of tumor cells. Some possible explanations of this very important loss of control are considered.
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PMID:The regulation of cell proliferation by calcium and cyclic AMP. 22 7

An improved basal medium is presented that required only minimal supplementation with dialyzed fetal bovine serum or bovine serum albumin and fetuin to be comparable to Ham's F-10, which requires 15% horse serum (HS) and 2.5% fetal bovine serum (FBS) for the growth and function of Y-1, mouse adrenal cortex tumor, cells. Cell monolayers maintained for up to 2 weeks without any protein supplementation have retained their steroid response to ACTH. The medium differs from Ham's F-10 in its buffer composition and higher calcium-ion concentration. This medium should be a useful adjunct to studies pertaining to steroid and lipid intermediary metabolism, the retention of a specialized physiological function in a chemically defined medium, and the mechanism of hormonal response.
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PMID:Improved basal medium for Y-1 mouse adrenal cortex tumor cells in culture. I. Dependence of growth and steroid response on calcium ion concentration. 23 59

Twenty patients with osteogenic sarcoma of the distal portion of the femur and the proximal portion of the tibia received chemotherapy (vincristine sulfate, methotrexate with leucovorin calcium rescue, [citrovorum factor; folinade calcium], and doxorubicin hydrochloride [Adriamycin]), followed by radical en bloc resection and prosthetic bone replacement. Histologic examination of surgical specimens obtained after chemotherapy showed variable degrees of tumor destruction and, in some cases, massive tumor necrosis, attesting to the profound effects of vigorous chemotherapy. This new therapeutic regimen, when feasible, may prove to be the treatment of choice in osteogenic sarcoma.
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PMID:Primary osteogenic sarcoma: pathologic aspects in 20 patients after treatment with chemotherapy en bloc resection, and prosthetic bone replacement. 29 12


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