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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies suggested that 3',5'-cyclic AMP (CAMP) may be involved in the regulation of cell proliferation and differentiation. Theophylline, an inhibitor of cyclic nucleotide phosphodiesterase, elevated intracellular cAMP. A melanotic clone of the B16 melanoma was treated with theophylline and studied in vitro and in vivo. With 12 hours after 1.0 mM theophylline was added to growing cultures, the number of cells incorporating tritiated thymidine (3-H-TDR) and the rate of uptake of 3-H-TDR into DNA were significantly reduced. After 7 days, the number of cells in the control cultures increased twenty-four times, whereas theophylline-treated cells increased only sixfold. Compared to the controls, the theophylline-treated cells contained ten times the melanin and an elevated cAMP content. Stimulation of melanogenesis and inhibition of proliferation increased progressively with duration of exposure to theophylline. After 5 days of culture with theophylline, cells were assayed for plating efficiency in theophylline-free medium. Although the number of colony-forming cells was unaffected by previous exposure to theophylline, the colonies were composed of fewer cells inoculated into syngeneic hosts were less tumorigenic than untreated cells. However, theophylline treatment of hosts bearing B16 tumors failed to reduce the tumor growth rate, and theophylline did not potentiate the growth inhibition resulting from treatment with the synthetic polyribonucleotide, polyinosinic-polycytidylic acid.
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PMID:Maturation and differentiation of B16 melanoma cells induced by theophylline treatment. 16 92

The role of adenosine 3',5'-monophosphate (cyclic AMP) in the regulation of mouse melanoma cell growth and differentiation was investigated. A variant melanoma (Cloudman S91-F) which displays a greater degree of transformation than the parental cell (Cloudman S91) was isolated. A correlation between cyclic AMP metabolism and transformation was made. Dibutyryl cyclic AMP depressed cell growth and increased pigmentation in both parental and variant cell lines. The parental cell line, however, was more responsive to melanocyte-stimulating hormone (MSH) which was found to affect cell growth and pigmentation by increasing cyclic AMP levels. The more transformed S91-F cell line contained lower levels of cyclic AMP than the parental cell line, and this fact correlated well with the higher degree of growth and lesser degree of pigmentation in the variant. Enzymatic analysis revealed that the hydrolysis of cyclic AMP in both cell lines was similar, while the adenylate cyclase activity of the variant cell line was lower than that of the parental cell line. Lineweaver-Burk plots demonstrated that the Km's for the enzymes in the two cell lines were the same but that the Vmax of the S91-F cell line was significantly less that that of the S91 cell line. Thus, the lesion in the S91-F cell which is responsible for its more transformed characteristics seems to be one which affects adenylate cyclase at the level of the cell membrane.
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PMID:The role of adenosine 3',5'-monophosphate in the transformation of Cloudman mouse melanoma cells. 17 19

Growth and melanization are intimately related in melanoma cells. MSH, by promoting elevated cyclic AMP levels, causes increases in melanization, cessation of growth, and gross morphologic changes in Cloudman S-91 melanoma cells. Growth inhibition results from high levels of cyclic AMP while growth stimulation occurs with lower levels. During melanization, oxidation products of tyrosine are generated which are toxic to the cells. Genetic studies have revealed that some of these processes are related through common biochemical pathways. This article reviews work of recent years on such regulatory mechanisms in melanoma.
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PMID:Factors regulating growth and pigmentation of melanoma cells. 17 4

Both dibutyryl cyclic AMP (DBcAMP) and cholera toxin promote the formation and elongation of processes of cultivated Greene hamster melanoma cells. The formation and maintenance of these processes, which contain many microtubules, are sensitive to colcemid and vinblastine. Tubulin was measured by [3H]colchicine binding and by acrylamide gel electrophoresis. We found that DBcAMP or cholera toxin increases the ratio of polymerized to unpolymerized tubulin but not the total amount of tubulin per cell. The sum of the lengths of microtubules per unit area was significantly greater in cells treated with DBcAMP than in control cells. Our findings support the hypothesis that cyclic AMP promotes the elongation of cell processes by stimulating the assembly of microtubules from existing tubulin.
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PMID:Microtubule assembly in cultivated Greene melanoma cells is stimulated by dibutyryl adenosine 3':5'-cyclic monophosphate or cholera toxin. 18 62

Melanoma cells treated with dibutyryl cyclic AMP (db cAMP) for 24 h resulted in dendritic cells possessing parallel assembled microtubules. A23187 treatments resulted in a biphasic response: Long term effects of the ionophore were characterized by small epitheloid cells while the immediate response produced elongated cells with parallel arranged 10 nm microgilaments, characteristic of dispersive melanocytes.
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PMID:Ionophore A23187 and dibutyryl cyclic AMP effects on cell shape and morphology of B-16 melanoma. 18 29

The proliferation of human melanocytes in vitro was stimulated by MSH. This stimulation was further intensified by the simultaneous addition of theophylline with MSH. Theophylline alone stimulated proliferation moderately. Dibutyryl cyclic AMP strongly stimulated the proliferation, but sodium butyrate, 5'-AMP and cGMP did not. The stimulation by dibutyryl cyclic AMP was continued up to 4 days so far tested. These findings are directly opposed to those on mouse melanoma cells in culture which responded with retarded growth to MSH and cyclic AMP. It is suggested that the difference of proliferation control may explain the different reaction of the melanocyte and the melanoma cells. The epidermal melanocytes seem to belong to the exceptional group of the cells which responded to cyclic AMP with accelerated proliferation.
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PMID:Stimulation by melanocyte stimulating hormone and dibutyryl adenosine 3'5'-cyclic monophosphate of DNA synthesis in human melanocytes in vitro. 18 88

Cultured Cloudman melanoma cells exposed either to dibutyryl 3':5'-cyclic AMP and theophylline or to cholera toxin bind significantly more 125I-labeled beta-melanocyte stimulating hormone (MSH) and fluorescein-labeled MSH than untreated cells. MSH binds to melanoma cells in the G2 phase of the cell cycle. The stimulation of MSH binding by dibutyryl cyclic AMP results from an increase in the number of MSH receptors per G2 cell and, to a lesser extent, from an increase in the number of G2 cells. The affinity of the receptors for MSH is not influenced by dibutyryl cyclic AMP.
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PMID:The number of receptors for beta-melanocyte stimulating hormone in Cloudman melanoma cells is increased by dibutyryl adenosine 3':5'-cyclic monophosphate or cholera toxin. 19 18

The in vitro proliferation of murine melanoma cell lines S91 and B16 was inhibited by retinoic acid and retinyl acetate. The inhibitory effects were dependent on retinoid concentration and increased from 55 and 30% at 10(-9) M retinoic acid to 85 and 82% at 10(-5) M retinoic acid for S91 and B16 melanoma cells, respectively. S91 melanoma cells were more sensitive than B16 melanoma cells to inhibition by either retinoid, and both cell lines were more sensitive to retinoic acid than to retinyl acetate. When exposed to 10(-5) M retinoic acid, the two cell types grew at the same rate as did control cells for 48 hours, whereupon the growth rates of retinoid-treated cells decreased. After 6 days, the number of cells in control cultures increased 140 times (S91 melanoma cells) and 265 times (B16 melanoma cells), whereas retinoic acid-treated cells increased only 14 times (S91 melanoma cells) and 40 times (B16 melanoma cells). The degree of growth inhibition by retinoic acid was not dependent on initial cell density. Cortisone and hydrocortisone failed to prevent or reduce the inhibitory effect of retinoic acid; the release of lysosomal acid phosphatase was not increased and the intracellular level of 3',5'-cyclic AMP in cells grown for 5 days in the presence of 10(-5) M retinoic acid was not elevated. Viability of S91 and B16 cells after 8 days' exposure to 10(-5) M retinoic acid was similar to that in control cultures. The reduced growth rate of retinoic acid-treated cells reversed to the control rate 48-72 hours after removal of retinoic acid from the growth medium.
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PMID:Characterization of the inhibitory effects of retinoids on the in vitro growth of two malignant murine melanomas. 20 60

The acute in vitro action of adrenocorticotropin (ACTH) and corticosterone alone and in combination were determined in the Cloudman S-91 melanoma grown in vivo. Hormone-treated melanoma dice (5-240 min) were analyzed for tyrosinase activity (EC 1.14.18.1), cyclic AMP (cAMP) and cyclic GMP (cGMP). ACTH elevated cAMP levels in the S-91 melanoma. However, these increases in cAMP were not accompanied by increased tyrosinase activity. Corticosterone depressed cAMP levels while stimulating tyrosinase activity. ACTH plus corticosterone produced an early cAMP peak followed by depression. ACTH plus corticosterone stimulated tyrosine activity coincident with the early cAMP peak followed by a drop in tyrosinase activity which was subsequently elevated. cGMP levels were not altered by any hormone treatment. The results indicate that cAMP is not the sole modulator of tyrosinase activity and suggest the interaction of ACTH, corticosterone and cAMP in the regulation of melanoma tyrosinase activity.
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PMID:Glucocorticoid modulation of adrenocorticotropin-induced melanogenesis in the Cloudman S-91 melanoma in vitro. 20 85

The ability of melanocyte stimulating hormone (MSH), adrenocorticotropic hormone (ACTH), and prostaglandin E1 (PGE1) to stimulate the accumulation of cyclic AMP was examined in intact mouse melanoma cells of varying metastatic potential. F1 cells (low metastatic potential) had significantly greater cyclic AMP levels in response to all three hormones than F5 (intermediate metastatic potential) and F10 (high metastatic potential) cells. The ranking of the response was as follows: MSH, F1 greater than F5 greater than F10, ACTH, F1 greater than F5 greater F10, PGE, F1 greater than F10 greater F5. In contrast to the above, the degree of hormonal stimulation of adenylate cyclase in broken cell preparations was virtually identical in all three melanoma cell lines. Control enzyme activity was depressed in both F5 and F10 relative to F1. The conflicting results between studies of intact vs. broken cell preparations could not be explained by increased cyclic AMP phosphodiesterase activity in F5 and F10 cells. We conclude that as the melanoma cells increase in metastatic potential, there is a significant loss in the ability of their cyclic AMP system to respond appropriately to hormonal stimuli.
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PMID:Hormonal activation of adenylate cyclase in mouse melanoma metastatic variants. 20 54


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