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

Data from cultured cells have suggested that cyclic AMP and cyclic GMP may be important determinants of cell growth and transformation. However, few studies have examined cyclic nucleotide content and metabolism in naturally occurring tumors of man. Accordingly, in the present study we compared cAMP and cGMP levels and metabolism in carcinomas of the human colon to those of the adjacent uninvolved mucosa after therapeutic resection of these tissues. The cAMP content of the tumors, determined in samples frozen 30 min after excision, was significantly lower than that of the adjacent mucosa, when expressed on the basis of tissue wet weight, protein, or DNA content. By contrast, the cGMP content of the tumors was higher than that of the surrounding mucosa if calculated on the basis of tissue wet weight, but this difference did not persist when correction was made for the higher protein or DNA content of the tumors. Incubation of slices of mucosa or tumor with or without theophylline in vitro increased tissue cAMP and cGMP content above levels observed in frozen samples of the same tissue. However, after such incubations cAMP levels in the tumors remained clearly below that of the mucosa, while cGMP content of the two tissues did not differ. The failure of theophylline to abolish differences in cAMP content and the comparable activities of high and low Km cAMP-phosphodiesterase in homogenates of the two tissues suggested that the lower cAMP content of the tumors was a consequence of diminished cAMP synthesis rather than enhanced degradation. This possibility was supported by the reduction in basal and maximal prostaglandin E1 (PGE1)-responsive adenylate cyclase activity found in tumor homogenates relative to those of mucosa, and the lower levels of cAMP in tumor slices after incubation of the tissues with a maximal dose of PGE1 and theophylline. Since NaF-responsive adenylate cyclase activity was not significantly reduced in the tumors, the lower basal and PGE1 activities may not be related to a deficiency of the catalytic unit of the cyclase complex in this tissue. The role of reduced activity of the adenylate cyclase-cAMP system and/or reduced tissue cAMP-to-cGMP ratios in the pathogenesis of colonic carcinoma is uncertain, but these changes might favor unregulated cellular proliferation.
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PMID:The content and metabolism of cyclic adenosine 3', 5'-monophosphate and cyclic guanosine 3', 5'-monophosphate in adenocarcinoma of the human colon. 17 89

ACTH stimulated steroidogenesis and cAMP (adenosine 3',5'-monophosphate) accumulation in an adrenocortical mouse tumor cell line (clone Y1) with Kd values which differed by more than one order of magnitude (5.2 X 10(-11) M and 7 X 10(-10) M, respectively). All of the cAMP formed in response to added ACTH appeared extracellularly in 5- or 30-min incubations. ACTH, at 5 and 10 muU/ml, stimulated steroidogenesis to 25% and 40% of maximum activity; and increased the extracellular accumulation of cAMP 1.4-fold and 2.3-fold, respectively. The effects of ACTH appeared to be via an action on intracellular ATP, specific for cAMP and dependent on an ACTH-sensitive adenylate cyclase system. These observations indicate that ACTH increases cAMP accumulation in Y1 cells at virtually all steroidogenic concentrations and suggest that cAMP is an essential component of ACTH-stimulated steroidogenesis.
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PMID:Steroidogenesis and extracellular cAMP accumulation in adrenal tumor cell cultures. 17 21

Literature on the hormonal effects of cell proliferation in the rat prostate is reviewed. Prostatic growth is initiated when subnormal levels of glandular cells are present. During this process, DNA synthesis and cell proliferation are stimulated by androgens. During the phase of negative feedback that occurs when the number of cells returns to normal, DNA synthesis is decreased and cell proliferation is markedly reduced, though secretion continues to be stimulated by androgen. Autophagia begins after the withdrawal of androgens, and is characterized by extensive autolysis of cells and loss of functional per formance. Dihydrotestosterone (DHT) may be necessary for inducing mitotic activity during the phase of initiation, though DNA synthesis and cell division are not affected unless there are fewer than the normal number of cells. If the regenerative process is completed, the cells undergo 1.8 doublings with a doubling time of 40 hours and a division cycle time of 20 hours. In the negative feedback phase, the cell division potential is determined by the total number of prostate cells at the start of proliferation. Autophagia eliminates a large number of prostatic cells, with those remaining being available for androgen stimulation. It is possible that the growth response of the prostate may be influenced by enzymes that form or metabolize dihydrotestosterone and also by cytoplasmic receptors. Changes in the rates of DNA synthesis and cell proliferation do not coincide with the concentrations of cAMP, cytoplasmic receptor, and nuclear receptor durin g phases of prostatic involution. This implies that cAMP and androgen r eceptors are not directly responsible for regulating DNA synthesis and cell proliferation. It is suggested that the activity of homeostatic constraint mechanisms depends on the presence of initiator, nullifier, and autophage genes, and that the absence of lessening of growth-function genes is associated with the development of neoplasia.
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PMID:Hormonal effects on cell proliferation in rat prostate. 18 Jun 81

Tissues from normal thyroid, euthyroid multinodular goiter, toxic goiter, Hashimoto's thyroiditis, thyroid adenoma, and carcinoma were examined for their content of deoxyribonucleic acid (DNA), thyroid peroxidase activity (TPA), thyroglobulin (TG), and adenosine 3',5'-cyclic monophosphate (cAMP). Compared with normal thyroids DNA was increased in the neoplastic tissues and decreased in euthyroid multinodular goiter. Quantitative changes of thyroglobulin were observed, especially in the thyroid tumors, and, in one case, immunoreactive 4S thyroglobulin-like protein was identified in the absence of 19S. TPA was grossly elevated in toxic goiter. This may be of significance in the pathogenesis of Graves' disease. TPA remained elevated even after adequate control of hyperthyroidism by preoperative PTU treatment. The cyclic AMP concentration in toxic goiter did not statistically differ from normal. This may indicate that extrathyroidal regulatory factors have a lesser role in the genesis and perpetuation of Graves' disease than otherwise believed. Cyclic AMP is known to exert a negative influence on tissue growth, and low concentrations in neoplasia have been reported. The values in the thyroid tumors studied were elevated, requiring further explanation.
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PMID:Thyroid peroxidase, thyroglobulin, cAMP and DNA in human thyroid. 18 98

Six cases of Cushing's syndrome with adrenocortical tumors which showed a variety of responsiveness to ACTH were investigated in relation to their clinical pictures and laboratory findings. Abnormal responses to ACTH in tumors was analyzed by in vitro experiments with surgically obtained tumor tissues, and the ACTH responsive mechanism of the tumors was discussed. An 8 hour intravenous ACTH infusion test showed that three of these patients were ACTH responsive, and the other three unresponsive. Histological observation of the tumors revealed that ACTH responsive tumors were adenomas and that ACTH unresponsive tumors were "black adenomas" in two and a carcinoma in one. To investigate possible factors which might account for these differences in ACTH responsiveness, tumor specimens of each one of the responsive and unresponsive adenomas, and a carcinoma were subjected to in vitro studies. When incubated with ACTH or cyclic AMP, tissue sections of a responsive adenoma enhanced cortisol secretion, while that of a black adenoma failed to show any change. Steroidogenesis by carcinoma sections were significantly suppressed in the presence of ACTH or cyclic AMP. Cycloheximide abolished a stimulatory effect of ACTH and cyclic AMP on steroidogenesis in a responsive adenoma without affecting its basal secretion of cortisol. Steroidogenesis by unresponsive tumors (an adenoma and a carcinoma) were decreased by cycloheximide. Since the conversion of cholesterol to pregnenolone, the rate limiting step in steroidogenesis, takes place in adrenal mitochondria, the effect of cyclic AMP on pregnenolone formation from 14C-cholesterol by mitochondrial fractions of these tumors was examined. Cyclic AMP stimulated pregnenolone formation by mitochondrial fraction of an ACTH responsive adenoma, while with that of an unresponsive adenoma pregnenolone formation was not affected. Pregnenolone formation by cancer mitochondria was significantly suppressed by cyclic AMP. These results suggest that the unresponsiveness to ACTH of these tumors might be explained by the ineffectiveness of cyclic AMP to stimulate pregnenolone formation by tumor mitochondria, and that the steroidogenic pathway in unresponsive tumors are in an enhanced state even without cyclic AMP. It should be mentioned that all unresponsive adenomas gave a characteristic appearance of a "black adenoma". Histologically, tumors were composed of compact cells with abundant lipofuscin granules. The possible relationship between the ACTH responsiveness of adrenocortical tumors and some clinical pictures caused by them was also noticed. ACTH unresponsive adenomas resulted in shorter duration, severer conditions of the disease and higher 17-ketosteroid excretion than responsive adenomas. The growth of unresponsive tumors seemed faster than that of responsive ones.
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PMID:[Studies on the responsiveness of human adrenocortical tumors to ACTH the clinical and experimental observations (author's transl)]. 18 66

Cyclic AMP levels in Ehrlich ascites tumor cells changed little after deprivation of cells of essential nutrients, serum, glucose and amino acids, deprival of each of which leads to marked inhibition of growth and protein synthesis. Cyclic AMP levels also changed little after the addition of these nutrients to deprived cells. Thus cyclic AMP is not likely to be the intracellular mediator for growth regulation by these three nutrients. Elevation of cyclic AMP levels for short periods by exposure of cells to choleratoxin or theophylline produced only slight changes in parameters of protein synthesis (polyribosome pattern and rate of [3H]leucine incorporation). An exposure for 1 day to dibutyryl cyclic AMP did not inhibit cell growth. However, prolonged exposure to dibutyryl cyclic AMP inhibited the multiplication of Ehrlich ascites cells both in suspension and in stationary cultures. No morphological effects were evident in the former; in the latter, cells attached firmly to the substratum and formed elongated cytoplasmic processes. Inhibition of cell multiplication by dibutyryl cyclic AMP was related to cell density and to serum concentration. Cells in dibutyryl cyclic AMP-containing media plated at low cell densities multiplied as rapidly as control cells. The final densities cells reached were determined by the serum concentration; in dibutyryl cyclic AMP-containing media these densities were about one-half those of respective control cells. Limitation of cell multiplication by dibutyryl cyclic AMP was reversed by the addition of serum, by resuspending cells at lower densities, or by resuspending cells in media without dibutyryl cyclic AMP. These findings suggested that dibutyryl cyclic AMP may affect the utilization of serum factors by cells. Dibutyryl cyclic AMP did not inactivate serum factors and did not change the rate at which cells depleted the growth medium of serum factors. Dibutyryl cyclic AMP may limit cell multiplication by increasing the cellular requirement for serum factors.
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PMID:Cyclic AMP and growth of Ehrlich ascites tumor cells. Lack of cyclic AMP elevation in nutritionally deprived cells and mechanism of retardation of growth by dibutryl cyclic AMP. 18 28

ACTH and cAMP stimulate steroidogenesis and the mitochondrial electron transport system for steroid hydroxylation in cultured mouse adrenal cortex tumor cells. During this stimulation, the biosynthesis of adrenodoxin, a non-heme iron protein which is one of the electron transport enzymes, was examined. 14C-labeled adrenodoxin was isolated by employing a purified rabbit antibody to bovine adrenodoxin. The antibody-adrenodoxin precipitates were further purified by acrylamide gel electrophoresis. It was observed that the biosynthesis of adrenodoxin was stimulated in response to ACTH induction and that this stimulation was completely inhibited with cycloheximide and partially inhibited with chloramphenicol. As a result, it was concluded that adrenodoxin requires both mitochondrial and cytosol ribosomal activities for its synthesis and integration into adrenal mitochondria.
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PMID:Biosynthesis of adrenodoxin in mouse adrenal tumor cells. 18 50

Cyclic AMP may be involved in the modulation of cell growth. The present work sought to further define differences between normal cells and tumor cells in their cyclic AMP system. Mouse embryo fibroblasts and murine bladder transitional epithelium tumor cells were grown in vitro; at various times, adenyl cyclase activity was assayed by measuring the conversion of [alpha32P]ATP to cyclic AM32P; stimulation by prostaglandin E1 or sodium fluoride was also determined. Base line and fluoride-stimulated enzyme activity were significantly greater in normal cells than tumor cells (P less than 0.01), and reached a peak at day 2; at confluency, levels in both systems decreased. Prostaglandin E1-stimulated levels, in contrast, were greater in tumor cells, there being a 10 fold greater relative stimulation in these cells compared to normal cells (P less than 0.01). Findings of a possibly greater sensitivity in these tumor cells may be important in a therapeutic modulation of tumor growth.
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PMID:Differences in adenylate cyclase activities in murine normal cells and bladder tumor cells in tissue culture. 18 32

The murine neuroblastoma appears to be a useful model for elucidating the mechanism of cellular differentiation. In tissue culture, MNB cells were induced to "irreversibly" differentiate into neuronal-like cells by DBcAMP alone or in combination with cAMP phosphodiesterase inhibitors: papaverine (Pap) and theophylline (Theo). Cells differentiated by DBcAMP, Pap, and Theo were no longer tumorgenic when reinoculated into animals of the host strain. In vivo, DBcAMP, Pap, and Theo caused a reduced tumor volume growth rate in animals with established tumors. Morphologically, this effect appears to be secondary to an arrest of cellular mitoses. Cells insensitive to these agents emerged after 3 to 4 days, and tumor growth accelerated to parallel the rate of the untreated tumors.
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PMID:Differentiation of mouse neuroblastoma cells in vitro and in vivo induced by cyclic adenosine monophosphate (cAMP). 18 80

There is evidence than adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) may have antagonistic actions on cell growth, with cAMP inhibiting and cGMP stimulating this process. However, reductions in cAMP and increases in cGMP are not charactersitic of all neoplastic tissues. Thus, benign and malignant tissues from hepatoma-bearing rats exposed to the hepatic carcinogen DL-ethionine have elevated rather than depressed cAMP, compared to control liver, and parenteral administration of this drug increases hepatic cAMP within hours. In the present study, the effects of ethionine ingestion on the hepatic content and metabolism of both cAMP and cGMP were examined sequentially in rats at 2 and then 6 wk intervals, from the initiation of drug administration until the development of hepatomas. After 2 wk, cAMP content of quick-frozen liver from rats receiving ethionine (E) was significantly increased (826 +/- 91 pmole/g wet weight) above that of liver from pair-fed controls (C, 415 +/- 44), whether calculated by tissue wet weight, protein, or DNA content. In benign tissue from E, higher cAMP was still evident after in vitro incubations of slices with 2 mM 1-methyl-3-iso-butylxanthine (MIX) and was associated with enhanced adenylate cyclase and unchanged high or low Km cAMP-phosphodiesterase activities. These findings are compatible with accelerated cAMP generation in liver from E. Protein kinase activity ratios were significantly increased in frozen liver from E (0.52 +/- 0.04 versus 0.36 +/- 0.03 in C), and the percent glycogen synthetase in the I form was clearly reduced (19% +/- 2% in E versus 47% +/- 5% in c). incubation of hepatic slices from E or C with MIX and/or 10 muM glucagon further increased cAMP and protein kinase activity ratios, data which imply higher effective, as well as total, cellular cAMP in E. Changes in cAMP metabolism and action observed at 2 wk persisted throughout the 38-wk period of drug ingestion. Adenylate cyclase activity, cAMP content, and protein kinase activity ratios of ethionine-induced hepatomas exceeded those of both the surrounding liver from tumor-bearing rats and that of control liver, but alterations in these parameters were qualitatively similar in both tissues from E. By contrast, while cGMP in quick-frozen surrounding liver from tumor-bearing rats (36 +/- 4 pmole/g wet weight) did not differ from that of control liver (30 +/- 3), cGMP in the hepatomas was increased. This change was evident in both frozen tumor (89 +/- 10) and in tumor slices incubated in vitro with MIX (C, 90 +/- 11; surrounding liver, 85 +/- 10; hepatoma 231 +/- 29). These results indicate that malignant conversion can occur in liver with a sustained elevation of both total and effective cAMP during the premalignant phase. The increase in cGMP detected in ethionine-induced hepatomas could also be a key determinant of malignant transformation in the model, although premalignant changes in cGMP were not apparent.
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PMID:Sequential alterations in the hepatic content and metabolism of cyclic AMP and cyclic GMP induced by DL-ethionine: evidence for malignant transformation of liver with a sustained increase in cyclic AMP. 18 92


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