Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the adrenocortical carcinoma cell, in contrast to normal isolated adrenal cells, 10 to 50 muunits of ACTH do not raise the level of adenosine cyclic 3':5'-monophosphate (cyclic AMP), protein kinase activity, and steroidogenesis. This indicates a lesion in the tumor adenylate cyclase system. Two-tenths to 10 mM cyclic AMP and guanosine cyclic 3':5'-monophosphate (cyclic GMP) which stimulate steroidogenesis in a normal cell, activate protein kinase activity in a concentration-response manner without any detectable rise in steroidogenesis in the adrenocortical carcinoma cell. Cycloheximide and actinomycin D do not inhibit the stimulation of the phosphorylation. These results suggest that the tumor cyclic nucleotide-dependent protein kinase activity is unrelated to steroidogenesis and is also not under the transcriptional or translational control steps. Curiously, muM concentrations of cyclic AMP, in contrast to cyclic GMP, stimulate protein kinase activity. In a normal cell, both cyclic AMP and cyclic GMP, in this concentration range, stimulate protein kinase without an increase in steroidogenesis. It is therefore proposed that, in contrast to the normal cell, there is an additional defect in cyclic GMP-dependent protein kinase.
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PMID:Metabolic regulation and relationship of endogenous protein kinase activity and steroidogenesis in isolated adrenocortical carcinoma cells of the rat. 18 48

Primary functional bovine adrenal cortical cell cultures have been developed to study the factors controlling adrenal cell growth. Cells were prepared by the collagenase technique and maintained in F-12 medium containing fetal calf serum and horse serum. Cells contained abundant lipid as demonstrated by staining with Oil Red O and showed strongly positive staining for delta5,3beta-hydroxysteroid dehydrogenase. ACTH inhibited DNA synthesis and stimulated steriodogenesis in these cells. Fibroblast growth factor (FGF) was shown to be a potent stimulator of the growth of normal bovine adrenal cortical cells maintained in tissue culture. The minimal effective dose of FGF was 1 ng/ml with maximal effects being observed at 100 ng/ml. The effect of FGF was dependent on the serum concentration. Inclusion of FGF in F-12 medium containing serum permitted cloning of functional bovine adrenal cortical cells from cultures seeded at low density (4 cells/cm2). ACTH inhibited the mitogenic effects of FGF. In addition to its mitogenic action, FGF is a migratory factor for bovine adrenal cortical cells. Though ACTH inhibited the mitogenic effects of FGF, it did not block the migratory activity. Epidermal growth factor did not affect the growth of either normal bovine adrenal or functional mouse adrenal tumor cells (Y-1) in tissue culture. FGF is the first direct mitogen identified for adrenal cortical cells; ACTH opposes this mitogenic action and functions directly as a differentiate function signal.
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PMID:Control of bovine adrenal cortical cell proliferation by fibroblast growth factor. Lack of effect of epidermal growth factor. 18 90

Protein kinase activity has been studied in four human adrenocortical tumors and compared to the one of the normal human adrenal. In two cases where the lack of action of ACTH was related to an anomaly of ACTH receptor, the protein kinase activity was normal. In the other two cases the ACTH receptor was normal, but the protein kinase activity was different from that of the normal adrenal. In one of these cases where the steroidogenesis response of isolated tumor cells to ACTH and DcAMP was higher than in normal adrenal, basal and cAMP stimulated protein kinase activities were significantly higher than those of the normal adrenal, but the activation constants of both nucleotides were similar to those of the normal gland. In the other case, the basal and the cAMP stimulated protein kinase activities were significantly lower, as well as the activation constant of cAMP. However, the binding affinity of 3H-cAMP was normal. Normal adrenal cytosol contains three protein kinases, as resolved by DEAE-cellulose, two of which designated I and II, are cAMP-dependent. The DEAE-cellulose chromatography of the last tumor showed a loss of isoenzyme II. In addition, the protein kinase eluted at the same molarity as that of isoenzyme I of the normal adrenal was not activated by cAMP. Therefore, the lack of response to ACTH of some adrenocortical human tumors may be attributed either to an anomaly of the ACTH receptor or to some defect of the cAMP-dependent protein kinase.
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PMID:Adenosine 3'5'-cyclic monophosphate dependent protein kinase in human adrenocortical tumors. 19 Feb 57

Corticotropin-releasing factor (CRF)-like activity in two different kinds of ACTH-producing tumors (human ectopic ACTH-producing colonic cancer and rat MtT/F4 tumor) was determined by an in vitro method using isolated normal rat pituitary cells. The ACTH content of the post mortem colonic cancer was 5.5 ng/g w.wt. The ACTH content of the medium of MtT/F4 tumor cells was 153+/-32 pg/10(5) cells. The ACTH content of MtT/F4 tumor cell suspensions was elevated with increasing doses of hypothalamic median eminence extract (HME). The response of MtT/F4 tumor cells to HME was suppressed by 1 mug/ml of dexamethasone. Extracts of colonic cancer, MtT/F4 tumor and HME produced elevation of the ACTH content of the medium of isolated rat pituitary cells. The CRF-like activities of two kinds of tumor extracts in multiple dilutions ran parallel to that of HME. The CRF-like activities were 0.037 HME equiv/mg w.wt in MtT/F4 tumor and 0.052 HME equiv/mg w.wt. in colonic cancer. These results demonstrated that CRF-like activity existed in these two kinds of ACTH-producing tumors.
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PMID:Corticotropin-releasing factor-like activity in ACTH producing tumors. 19 Feb 59

ACTH producing cells in islet cell carcinoma associated with Cushing's syndrome were studied by an improved immunoperoxidase as well as immunofluorescence technique. The cells which contained ACTH antigen were distributed throughout the tumor tissue of both primary and metastatic lesions in rather small numbers. In the small cancer nests they were present in an irregular or mosaic pattern and, on the contrary, they tend to line along the margin in the larger nests. The intracytoplasmic localization of the ACTH antigen was characteristically demonstrated in the infranuclear area of the tumor cells, closely simulating that of the argentaffin granules of the enterochromaffin cells. The electron microscopic observation identified membrane enclosed, cored granules, 200-300 nm in diameter, present in clusters in the infranuclear area of some tumor cells, which were considered corresponding well to the ACTH positive cells in immune staining.
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PMID:Immunohistological study on the ACTH producing islet cell carcinoma of the pancreas. 19 53

Since 1965, 118 glioblastoma and 18 malignant astrocytomas of the adult have been treated by concentrated irradiation after a more or less complete surgical excision of the tumor. Three types of irradiation have been used; at present 3 600 rads whole brain irradiation are delivered in 2 series of 1 800 rads over 3 days 20 to 30 spaced a part. All patients receive ACTH and the tolerance has been excellent. The results of this rapid palliative therapy are quite comparable to those of more classical irradiation. Because of the very short survival of these patients, it would appear advantageous to treat them in as short a time interval as possible.
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PMID:[Concentrated irradiation of malignant astrocytoma and glioblastoma]. 19 98

ACTH stimulates the incorporation of 14C-leucine into proteins of adrenal tumor cells in culture. This stimulation though about 20% over controls is statistically significant. Cyclic AMP did not reproduce the stimulation observed with ACTH.
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PMID:[Stimulation by ACTH of protein synthesis in cultured adrenal cells. Absence of an effect by cyclin AMP]. 19 54

This article tries to give criteria for the two possible modes of treatment of the pituitary-dependent Cushing's syndrome. Patients (n = 6) who show no secondary complications on Cushing's disease should undergo implantation of 90Y and/or 192Ir into the pituitary gland. After implantation, the excessive secretion of ACTH is suppressed to normal values. The symptoms of Cushing's syndrome disappear. Following the operation, certain patients must also receive hormonal replacement therapy. Fertility is not always preserved. Total adrenalectomy as the alternative procedure is performed in adults with advanced symptoms of the disease (n = 3) and in children (n = 3). Following removal of the adrenal glands, the symptoms of Cushing's syndrome disappear. The appearance of Nelson's tumor after adrenalectomy (10% in the literature) is discussed.
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PMID:[Criteria for surgical therapy of hypothalamo-hypophyseal Cushing's syndrome]. 19 73

The ability of cytochalasin B to inhibit the steroidogenic response of mouse adrenal tumor cells (Y-1) to adrenocorticotropin (ACTH) was examined with two aims: to consider the specificity of the inhibitor and to determine at what point(s) in the steroidogenic pathway it acts. Cytochalasin B did not inhibit protein synthesis or transport of [3H]-cholesterol into the cells nor did it alter total cell concentration of ATP. Together with previous evidence, this suggests that the effects of cytochalasin observed are relatively specific in these cells. Cytochalasin inhibits the increase in conversion of [3H]cholesterol to 20alpha-[3H]dihydroprogesterone (20alpha-hydroxypregn-4-en-3-one: a major product of the steroid pathway in Y-1 cells) produced by ACTH but does not inhibit conversion of cholesterol to pregnenolone by mitochondrial and purified enzyme preparations from Y-1 cells and bovine adrenal, respectively. Cytochalasin does not inhibit the conversion of pregnenolone to 20alpha-dihydroprogesterone but was shown to inhibit increased transport of [3H]cholesterol to mitochondria resulting from the action of ACTH. These findings indicate that cytochalasin acts after cholesterol has entered the cells and before it is subjected to side-chain cleavage in mitochondria. In view of the known action of cytochalasin on microfilaments, it is proposed that these organelles are necessary for the transport of cholesterol to the mitochondrial cleavage enzyme and that at least one effect of ACTH (and cyclic AMP) is exerted upon this transport process. The specificity of the effects of cytochalasin is considered in relation to this conclusion.
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PMID:Response of adrenal tumor cells to adrenocorticotropin: site of inhibition by cytochalasin B. 19 28

Locally recurrent, poorly differentiated carcinoma of the prostate was associated with hypokalemic alkalosis, marked hypernatremia, diabetes mellitus of recent onset, and hyperosmolar syndrome. These findings, with mild hypertension, in the absence of clinical features of Cushing's syndrome, suggested an ectopic ACTH syndrome. Plasma ACTH and cortisol levels were markedly elevated, and failed to suppress in response to either low or high-dose dexamethazone administration. The patient's condition deteriorated rapidly. Autopsy findings included carcinoma extensively infiltrating the prostate with extension to the urinary bladder, and metastases confined to the pelvic nodes and soft tissues. The adrenal glands weighed 23 g and showed diffuse hyperplasia. Extract of the prostatic tumor was analyzed for ACTH and showed approximately 40 times normal plasma levels (or about 4,010 pg/g of tissue); ultrastructural features showed secretory granules consistent with ACTH content of the tumor cells. Such cells were positive when stained for ACTH by peroxidase-tagged immunochemical methods. The case fulfills all established criteria for relating excess corticosteroid production and nonpituitary tumors.
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PMID:Ectopic ACTH, prostatic oat cell carcinoma, and marked hypernatremia. 19 43


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