Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

Previous studies have shown that vitamin E supplementation inhibits murine melanoma cell growth in vitro. In this study, malignant murine melanoma (BL6) and non-malignant monkey kidney (LLCMK) cells were supplemented with 1-10 micrograms/ml D-alpha-tocopherol acid succinate (vitamin E succinate). The effect of vitamin E succinate supplementation on growth as well as the levels of adenylate cyclase activity, prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cAMP) were determined in these cells. Results from these studies indicated a significant inhibition of BL6 cell growth at 5 (P < 0.025), 7 and 10 micrograms/ml (P < 0.001) vitamin E succinate supplementation, while LLCMK cells showed no significant increase or decrease in growth following vitamin E succinate supplementation. BL6 cells supplemented with 7 and 10 micrograms/ml vitamin E succinate showed a marked increase in PGE2 levels, with a significant increase (P < 0.025) occurring at 10 micrograms/ml. Adenylate cyclase activity in BL6 cells was also significantly increased at vitamin E succinate concentrations of 7 (P < 0.05) and 10 micrograms/ml (P < 0.05), respectively, and supplementation of these cells with 5 (P < 0.05), 7 and 10 micrograms/ml (P < 0.001) vitamin E succinate resulted in a significant increase in the levels of cAMP, while LLCMK cells showed no significant increase or decrease in PGE2, adenylate cyclase activity or cAMP levels over the vitamin concentrations tested.
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PMID:The role of adenylate cyclase, cAMP and PGE2 in the in vitro growth regulation of murine melanoma cells by vitamin E. 883 67

Malignant murine melanoma (BL6) cells cultured in vitro were supplemented with indomethacin (0.15 microM) and varying levels (1-10 micrograms/ml) of vitamin E succinate. The effect of combined indomethacin and vitamin E succinate treatment on the growth as well as the levels of adenylate cyclase activity, prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cAMP) were determined in these cells. BL6 cells supplemented with 0.15 microM indomethacin and 1-10 micrograms/ml vitamin E succinate showed a significant (P < or = 0.05) decrease in growth at 1 microgram/ml vitamin E succinate, while at 3-10 micrograms/ml, no significant increase or decrease in growth was observed when compared to control cultures (OE). Results from studies of adenylate cyclase activity in BL6 cells showed no significant increase or decrease in enzyme activity, nor were the levels of PGE2 and cAMP affected when the cells were supplemented with 0.15 microM indomethacin and 1-10 micrograms/ml vitamin E succinate.
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PMID:Effect of vitamin E and indomethacin treatment on adenylate cyclase activity, PGE2 and cAMP levels in murine melanoma cells. 905 24

An analogue of human melanin-concentrating hormone (MCH) suitable for radioiodination was designed in which Tyr13 and Val19 of the natural peptide were replaced by phenylalanyl and tyrosyl residues: [Phe13, Tyr19]-MCH. The peptide was synthesized by the continuous-flow solid-phase methodology using Fmoc-strategy and polyhipe PA 500 and PEG-PS resins. The linear MCH peptides with either acetamidomethyl-protected or free cysteinyl residues were purified to homogeneity and cyclized by iodine oxidation, yielding the final product with the correct molecular weight of 2434.61. Radioiodination of the C-terminal tyrosine was carried out enzymatically using solid-phase bound glucose oxidase/lactoperoxidase, followed by purification on a reversed-phase mini-column and by high-pressure liquid chromatography. The resulting [125I]-[Phe13, Tyr19]-MCH tracer was the first radiolabelled MCH peptide suitable for radioreceptor assay: saturation binding analysis using mouse G4F-7 melanoma cells demonstrated the presence of 1090 MCH receptors per cell. The dissociation constant (KD) was 1.18 x 10(-10) M, indicating high-affinity MCH receptors on these cells. MCH receptors were also found in other cell lines such as mouse B16-F1 and G4F and human RE melanoma cells as well as in PC12 and COS-7 cells. Competition binding analyses with a number of other peptides such as alpha-MSH, neuropeptide Y, substance P and pituitary adenylate cyclase activating peptide, demonstrated that the binding to the MCH receptor is specific. Atrial natriuretic factor was found to be a weak competitor of MCH, indicating topological similarities between MCH and ANF when interacting with MCH receptors.
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PMID:Synthesis and iodination of human (phenylalanine 13, tyrosine 19) melanin-concentrating hormone for radioreceptor assay. 922 84

We have previously reported that neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) successfully inhibited Matrigel invasion and haptotactic migration of B16-BL6 melanoma cells towards both fibronectin and laminin without affecting their growth. In the present study, we investigated the inhibitory mechanism of tumor cell motility by alpha-MSH. Alpha-MSH significantly blocked the autocrine motility factor (AMF)-enhanced cell motility. However, alpha-MSH did neither prevent the secretion of AMF from B16-BL6 cells nor alter the expression level of AMF receptor (gp78). On the other hand, alpha-MSH induced the secretion of the motility inhibitory factor(s) from B16-BL6 cells in a concentration- and time-dependent manner. The induction of the motility inhibitor(s) was proportional to increasing levels of intracellular cAMP induced by alpha-MSH as well as forskolin, and the activity was abolished by an adenylate cyclase inhibitor, 2',5'-dideoxyadenosine (DDA). The motility-inhibiting activity in conditioned medium (CM) from alpha-MSH-treated B16-BL6 cells was found to have a m.w. below 3 kDa after fractionation. This activity was abolished by boiling but insensitive to trypsin. The treatment of tumor cells with cycloheximide reduced the activity in alpha-MSH-stimulated CM. Our results suggest that alpha-MSH inhibited the motility of B16-BL6 cells through induction of autocrine factor(s).
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PMID:Induction of autocrine factor inhibiting cell motility from murine B16-BL6 melanoma cells by alpha-melanocyte stimulating hormone. 1007 23

Bordetella pertussis secretes an invasive adenylate cyclase toxin, CyaA, that is able to deliver its N-terminal catalytic domain into the cytosol of eukaryotic target cells directly through the cytoplasmic membrane. We have shown previously that recombinant CyaA can be used to deliver viral CD8+ T cell epitopes to the MHC-class I presentation pathway to trigger specific CTL responses in vivo. In the present study, we show that mice immunized with a detoxified but still invasive CyaA carrying a CD8+ T cell epitope of OVA developed strong epitope-specific CTL responses, which kill tumor cells expressing this Ag. Treating mice with this recombinant molecule after the graft of melanoma cells expressing OVA induced a strong survival advantage compared with control animals. To our knowledge, this study represents the first demonstration that a nonreplicative and nontoxic vector carrying a single CTL epitope can stimulate efficient protective and therapeutic antitumor immunity.
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PMID:Therapy of murine tumors with recombinant Bordetella pertussis adenylate cyclase carrying a cytotoxic T cell epitope. 1020 41

Proteins that bind to G protein-coupled receptors have recently been identified as regulators of receptor anchoring and signaling. In this study, actin-binding protein 280 (ABP-280), a widely expressed cytoskeleton-associated protein that plays an important role in regulating cell morphology and motility, was found to associate with the third cytoplasmic loop of dopamine D(2) receptors. The specificity of this interaction was originally identified in a yeast two-hybrid screen and confirmed by protein binding. The functional significance of the D(2) receptor-ABP-280 association was evaluated in human melanoma cells lacking ABP-280. D(2) receptor agonists were less potent in inhibiting forskolin-stimulated cAMP production in these cells. Maximal inhibitory responses of D(2) receptor activation were also reduced. Further yeast two-hybrid experiments showed that ABP-280 association is critically dependent on the carboxyl domain of the D(2) receptor third cytoplasmic loop, where there is a potential serine phosphorylation site (S358). Serine 358 was replaced with aspartic acid to mimic the effects of receptor phosphorylation. This mutant (D(2)S358D) displayed compromised binding to ABP-280 and coupling to adenylate cyclase. PKC activation also generated D(2) receptor signaling attenuation, but only in ABP-containing cells, suggesting a PKC regulatory role in D(2)-ABP association. A mechanism for these results may be derived from a role of ABP-280 in the clustering of D(2) receptors, as determined by immunocytochemical analysis in ABP-deficient and replete cells. Our results suggest a new molecular mechanism of modulating D(2) receptor signaling by cytoskeletal protein interaction.
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PMID:Modulation of dopamine D(2) receptor signaling by actin-binding protein (ABP-280). 1069 83

The intraocular pressure-lowering drug latanoprost, a phenyl-substituted analogue of prostaglandin F2 alpha (PGF2 alpha), increases iris pigmentation in a small number of patients. In theory, this could be due to increased melanogenesis or melanocyte proliferation. To distinguish these two possibilities, the present study examined the effects of latanoprost on tyrosinase activity (the rate-limiting step for melanin synthesis) and mitotic index of cultured melanoma lines. Murine cutaneous melanoma lines (S91 and B16), and human uveal (OCM1, OCM3, and OM431) and cutaneous (SK-MEL5 and M21) melanoma lines were cultured with PGE1, PGE2, PGF2 alpha, latanoprost, or the adenylate cyclase stimulating agent forskolin. After treatment, tyrosinase was assayed with respect to its dopa oxidase activity using a colorimetric assay. PGE1, PGE2, PGF2 alpha, and latanoprost greatly increased tyrosinase activity in murine melanoma lines and caused small increases in tyrosinase activity in human uveal and cutaneous melanoma lines. Similar results were obtained with the cAMP-elevating compound forskolin. Cyclic AMP content, as determined by an enzyme-linked immunoassay, was similarly increased by all treatments, with forskolin being the most potent stimulator. Since the species difference in tyrosinase activity was observed without an apparent difference in induction of cAMP, latanoprost would appear to induce tyrosinase activity through a non-cAMP-dependent pathway. Finally, latanoprost and PGF2 alpha did not enhance the mitotic index of human uveal or cutaneous melanoma lines, measured by [6-3H] thymidine uptake, although they increased the mitotic index of one murine cutaneous line. Given that latanoprost induced tyrosinase activity, but did not increase the mitotic index in any of the human melanoma lines studied, this suggests that the in vivo iris pigmentation side effect of latanoprost may not result from increased cell division, but from elevated tyrosinase activity.
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PMID:Effects of latanoprost on tyrosinase activity and mitotic index of cultured melanoma lines. 1087 May 14

The terminal differentiation of malignant melanoma cells is known to be induced by activating cAMP signaling pathway with alpha-MSH or cAMP analogues. However, sustained activation of cAMP signaling system that induces the differentiation of melanoma cells, also induces the desensitization of the pathway at the receptor level. Nevertheless, the adaptation of adenylate cyclase (AC) expression by sustained activation of cAMP signaling system has not been clearly understood. This study was performed to examine whether the sustained activation of cAMP system induce changes in the expression AC isoforms as an adaptation mechanism. Treatment of B16/F10 murine melanoma cells with 100 mM forskolin for 6 days resulted in differentiation, melanin accumulation and increased expression of tyrosine hydroxylase mRNA. In the forskolin-treated melanoma cells, change in expression of various AC isoform at the transcription level was detected by reverse-transcription polymerase chain reaction (RT-PCR). Expression of AC isoform mRNA: ACI, III, VI, VII, and IX increased to the level of 196-392% of the control whereas the level of ACII was decreased by 30%. The cAMP concentration was increased both in basal and alpha-MSH stimulated cells, but the AC activity was decreased in the forskolin treated cells. Thus, these results suggest that sustained activation of cAMP system induces differential expression of AC isoforms, which results in increase of cAMP accumulation.
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PMID:Multi-facet expressions of adenylate cyclase isoforms in B16-F10 melanoma cells differentiated by forskolin treatment. 1119 Feb 77

The ACTH receptor is the type 2 (MC2R) among the melanocortin receptor family and is expressed almost exclusively in the adrenal cortex. The human MC2R (hMC2R) was very difficult to express in heterologous cell lines. We have succeeded in transient and stable expression of hMC2R using the M3 melanoma cells. Moreover, we have found that the expressed hMC2R in M3 cells showed similar ACTH binding affinity and coupling to adenylate cyclase as the MC2R of normal human adrenal cells, contrarily to most of the other expression cell models. In these conditions, we have been able to test several mutant hMC2R described in patients with the familial glucocorticoid deficiency syndrome (FGD) using this cell line.
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PMID:Functional expression of the human ACTH receptor gene. 1119 27

DEC1 (BHLHB2)/Stra13/Sharp2, a basic helix-loop-helix (bHLH) transcription factor has been suggested to be involved in the control of proliferation and/or differentiation of several cells including nerve cells, fibroblasts and chondrocytes. In the present study, we examined the effect of parathyroid hormone (PTH), dibutyryl cAMP (Bt2cAMP) and forskolin on the expression of DEC1 in various cells. In rabbit chondrocyte cultures, PTH or Bt2cAMP increased the DEC1 mRNA level within 1 h. Thereafter, the DEC1 mRNA level rapidly decreased to the basal level at 3 h, and increased at 6-24 h. In cultures of a mouse embryo prechondrogenic cell line ATDC5, PTH or forskolin, an activator of adenylate cyclase, also increased the DEC1 mRNA level within 1 h. Furthermore, in all evaluated cell lines of human fibroblasts, canine epithelial cells, human carcinoma, human glioblastoma and human melanoma, Bt2cAMP increased the DEC1 mRNA level within 1-3 h. Studies with actinomycin D and cycloheximide indicated that the enhancement of DEC1 mRNA by cAMP was not due to mRNA stabilization and did not require new protein synthesis. These findings suggest that DEC1 is a novel direct target for cAMP in wide types of cells, and that the bHLH protein is involved in the control of gene expression in cAMP-activated cells.
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PMID:Induction of basic helix-loop-helix protein DEC1 (BHLHB2)/Stra13/Sharp2 in response to the cyclic adenosine monophosphate pathway. 1143 22


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