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)

Pyrrolo[1,2-a]benzimidazole(PBI)-based aziridinyl quinones cleave DNA under reducing conditions specifically at G + A bases without any significant cleavage at C + T bases. The postulated mechanisms involve phosphate alkylation by the reductively activated aziridine to afford a hydrolytically labile phosphotriester as well as the classic N(7) purine alkylation followed by depurination and backbone cleavage. Evidence is presented that the phosphate alkylation mechanism could contribute. The PBIs possess a unique spectrum of cytotoxicity against cancer cells (inactive against leukemia but active against nonsmall cell lung, colon, CNS, melanoma, ovarian, and renal cancers). Also reported are results of in vivo antitumor activity screens.
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PMID:Pyrrolo[1,2-a]benzimidazole-based aziridinyl quinones. A new class of DNA cleaving agent exhibiting G and A base specificity. 823 90

We describe a serine phosphorylation of the putative metastasis suppressor protein Nm23, and present evidence of its relevance to the signal transduction and tumor metastatic processes. Nm23 was previously demonstrated to exhibit nucleoside diphosphate kinase (NDPK) activity, which transfers a phosphate among nucleoside tri- and diphosphates via an Nm23-phospho-histidine intermediate. Recent data have dissociated the NDPK activity of Nm23 from its phenotypic effects; therefore we have asked whether Nm23 possesses additional biochemical functions. An acid-stable (nonhistidine) phosphorylation was identified on autophosphorylated purified recombinant Nm23 proteins and [32P]orthophosphate-labeled human breast carcinoma and murine melanoma Nm23. Phosphoamino acid analysis identified serine as the acid-stable phosphorylation and serine 44 as the major site of phosphorylation. The acid stable phosphorylation (serine) of Nm23 was inhibited by cAMP in vitro and forskolin in vivo, suggesting that this phosphorylation pathway is regulated in signal transduction. No effect of cAMP was observed on Nm23 NDPK activity. Once phosphorylated, Nm23-phosphoserine can release free phosphate in vitro. The biological relevance of the novel phosphorylation identified herein is suggested by the direct correlation of in vivo Nm23 acid-stable phosphorylation levels, but not Nm23 NDPK activity, with suppression of tumor metastatic potential among control and nm23-1 transfected murine melanoma cells.
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PMID:A serine phosphorylation of Nm23, and not its nucleoside diphosphate kinase activity, correlates with suppression of tumor metastatic potential. 824 15

Six human melanoma xenograft lines grown s.c. in BALB/c-nu/nu mice were subjected to 31P-nuclear magnetic resonance (31P-NMR) spectroscopy in vivo. The following resonances were detected: phosphomonoesters (PME), inorganic phosphate (Pi), phosphodiesters (PDE), phosphocreatine (PCr) and nucleoside triphosphate gamma, alpha and beta (NTP gamma, alpha and beta). The main purpose of the work was to search for possible relationships between 31P-NMR resonance ratios and tumour pH on the one hand and blood supply per viable tumour cell on the other. The latter parameter was measured by using the 86Rb uptake method. Tumour bioenergetic status [the (PCr + NTP beta)/Pi resonance ratio], tumour pH and blood supply per viable tumour cell decreased with increasing tumour volume for five of the six xenograft lines. The decrease in tumour bioenergetic status was due to a decrease in the (PCr + NTP beta)/total resonance ratio as well as an increase in the Pi/total resonance ratio. The decrease in the (PCr + NTP beta)/total resonance ratio was mainly a consequence of a decrease in the PCr/total resonance ratio for two lines and mainly a consequence of a decrease in the NTP beta/total resonance ratio for three lines. The magnitude of the decrease in the (PCr + NTP beta)/total resonance ratio and the magnitude of the decrease in tumour pH were correlated to the magnitude of the decrease in blood supply per viable tumour cell. Tumour pH decreased with decreasing tumour bioenergetic status, and the magnitude of this decrease was larger for the tumour lines showing a high than for those showing a low blood supply per viable tumour cell. No correlations across the tumour lines were found between tumour pH and tumour bioenergetic status or any other resonance ratio on the one hand and blood supply per viable tumour cell on the other. The differences in the 31P-NMR spectrum between the tumour lines were probably caused by differences in the intrinsic biochemical properties of the tumour cells rather than by the differences in blood supply per viable tumour cell. Biochemical properties of particular importance included rate of respiration, glycolytic capacity and tolerance to hypoxic stress. On the other hand, tumour bioenergetic status and tumour pH were correlated to blood supply per viable tumour cell within individual tumour lines. These observations suggest that 31P-NMR spectroscopy may be developed to be a clinically useful method for monitoring tumour blood supply and parameters related to tumour blood supply during and after physiological intervention and tumour treatment. However, clinically useful parameters for prediction of tumour treatment resistance caused by insufficient blood supply can probably not be derived from a single 31P-NMR spectrum since correlations across tumour lines were not detected; additional information is needed.
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PMID:31P-nuclear magnetic resonance spectroscopy in vivo of six human melanoma xenograft lines: tumour bioenergetic status and blood supply. 826 Mar 56

Sphingosine-1-phosphate (Sph-1-P) has been implicated as a second messenger in control of cell motility and proliferation (e.g., Sadahira Y, et al., PNAS 89:9686, 1992; Olivera A & Spiegel S, Nature 365:557, 1993). The control mechanism for its synthesis, as catalyzed by sphingosine kinase, is crucial in signal transduction. Synthesis of Sph-1-P in Balb/c 3T3 fibroblasts (A31 variant) is strongly up-regulated by brief treatment of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA). Level of Sph-1-P in PKC-depleted cells is 10-fold higher than in undepleted cells, and a further 5-fold increase occurs after treatment with TPA. In Swiss 3T3 and B16 melanoma cells, Sph-1-P level was unaffected by TPA treatment. Thus, the effect of TPA on Sph-1-P synthesis appears to be cell type-specific.
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PMID:Regulatory effect of phorbol esters on sphingosine kinase in BALB/C 3T3 fibroblasts (variant A31): demonstration of cell type-specific response--a preliminary note. 829 9

The melanocyte-stimulating hormone (alpha-MSH) used at 10(-6)-5 x 10(-8) M concentrations inhibited the growth of amelanotic cells of human malignant melanoma BRO and influenced cell morphology without any effect on melanization or tyrosinase activity. Inhibition of tumour cell growth was accompanied by marked elevation of intracellular cAMP levels but not that of cGMP. Dibutyryl-cAMP and the cAMP-dependent protein kinase A inhibitor also inhibited the cell growth. alpha-MSH increased mono-, di- and 1.4.5-myoinositol triphosphate concentrations and influenced the activities of phosphatidylinositol kinase and phosphatidylinositol-4-phosphate kinase determining phosphatidylinositol-4-phosphate kinase and phosphatidylinositol-4.5-diphosphate levels. Myoinositol phosphate concentrations changed on a second scale and levelled off by the 3rd-5th min, whereas that of cAMP increased drastically by the 30th min.
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PMID:[Melanocyte-stimulating hormone induces growth of human malignant melanoma amelanotic cells with a change in cAMP, phosphatidylinositols, and inositol phosphate concentration]. 838 47

1. The distributions and rates of transfer of carbon isotopes from a selection of specifically labelled ketosugar-phosphate substrates by exchange reactions catalyzed by the pentose and photosynthetic carbon-reduction-pathway group-transferring enzymes transketolase, transaldolase and aldolase have been measured using 13C-NMR spectroscopy. 2. The rates of these exchange reactions were 5, 4 and 1.5 mumol min-1 mg-1 for transketolase exchange, transaldolase exchange and aldolase exchange, respectively. 3. A comparison of the exchange capacities contributed by the activities of these enzymes in three in vitro liver preparations with the maximum non-oxidative pentose pathway flux rates of the preparations shows that transketolase and aldolase exchanges exceeded flux by 9-19 times in liver cytosol and acetone powder enzyme preparations and by 5 times in hepatocytes. Transaldolase was less effective in the comparison of exchange versus flux rates: transaldolase exchange exceeded flux by 1.6 and 5 in catalysis by liver cytosol and acetone powder preparations, respectively, but was only 0.6 times the flux in hepatocytes. 4. Values of group enzyme exchange and pathway flux rates in the above three preparations are important because of the feature role of liver and of these particular preparations in the establishment, elucidation and measurement of a proposed reaction scheme for the fat-cell-type pentose pathway in biochemistry. 5. It is the claim of this paper that the excess of exchange rate activity (particularly transketolase exchange) over pathway flux will overturn attempts to unravel, using isotopically labelled sugar substrates, the identity, reaction sequence and quantitative contribution of the pentose pathway to glucose metabolism. 6. The transketolase exchange reactions relative to the pentose pathway flux rates in normal, regenerating and foetal liver, Morris hepatomas, mammary carcinoma, melanoma, colonic epithelium, spinach chloroplasts and epididymal fat tissue show that transketolase exchange may exceed flux in these tissues by factors ranging over 5-600 times. 7. The confusion of pentose pathway theory by the effects of transketolase exchange action is illustrated by the 13C-NMR spectrum of the hexose 6-phosphate products of ribose 5-phosphate dissimilation, formed after 30 min of liver enzyme action, and shows 13C-labelling in carbons 1 and 3 of glucose 6-phosphate with ratios which range over 2.1-6.4 rather than the mandatory value of 2 which is imposed by the theoretical mechanism of the pathway.
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PMID:Exchange reactions catalyzed by group-transferring enzymes oppose the quantitation and the unravelling of the identify of the pentose pathway. 847 19

Studies have been conducted in mice (B6C3F1) and rats (Sprague Dawley, Fischer 344) to investigate the adjuvancy potential of silicone mammary gel and the low molecular weight silicone fluid, octamethylcyclotetrasiloxane (D4). Dependent on the experimental conditions employed, a divergent data profile emerges. If the antigen (bovine serum albumin, BSA) is emulsified with either the gel or the D4 prior to intramuscular immunization, an amplified anti-BSA IgG antibody response, as measured by multipoint ELISA methodology, is noted over the 8 week measurement period. In parallel studies, a variety of non-silicone personal care ingredients (lanolin, white mineral oil, isopropyl palmitate) were also capable of amplifying this humoral response relative to the non-adjuvant phosphate buffered saline control. These observations are consistent with the empirical knowledge that hydrophobic substances tend to augment immune responses. However, under conditions in which the antigen is not blended with the silicone prior to immunization, normal immune responses are noted. In short (10 day) and long (180 day) term gel implant studies, the optimal IgM and IgG antibody responses, as determined in the antibody forming cell assay, were equivalent between the gel implanted and control animals. Moreover, under similar exposure conditions, no adjuvancy was noted in the three Host Resistance models (B16F10 Melanoma, Listeria monocytogenes, and Streptococcus pneumoniae) tested. Antibody forming cell studies conducted after 28 days of oral or inhalation exposure to D4 have also yielded responses similar to the non-silicone exposed vehicle controls. Collectively, these data suggest that in the absence of premixing the antigen with the silicone test material, there does not appear to be any silicone induced adjuvant response.
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PMID:The adjuvancy of silicones: dependency on compartmentalization. 856 49

Sphingosine-1-phosphate (Sph-1-P), the initial product of sphingosine (Sph) catabolism, has been reported to inhibit motility of mouse melanoma B16/F1 and other types of cells at very low concentrations (10-100 nM). Sph-1-P (100 nM-1 microM) inhibited pseudopodium formation by blocking polymerization and reorganization of actin filaments in newly formed pseudopodia, and reduced F-actin by approximately 25% in F1 cells. A pyrene-labeled actin nucleation assay revealed that Sph-1-P (100 nM) inhibits actin nucleation mediated by F1 cell plasma membranes. These results suggest that Sph-1-P interacts with molecules associated with actin nucleation to inhibit reorganization of pseudopodium formation and cell motility.
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PMID:Sphingosine-1-phosphate inhibits actin nucleation and pseudopodium formation to control cell motility of mouse melanoma cells. 861 51

1. Galanin is a 29 (in humans 30) amino acids long neuropeptide with mostly inhibitory, hyperpolarizing actions. 2. Differential structural requirements of truncated forms of galanin and differential agonist/antagonist behaviour of chimeric peptides, high affinity galanin receptor ligands suggest the presence of pharmacologically distinct galanin receptor subtypes. 3. The galanin receptor from human Bowes melanoma cell line--a member of G-protein coupled receptor superfamily--has been cloned. 4. Galanin acts via Gi/G(o) proteins inhibiting cAMP production, inositol phosphate turnover, opening K+ channels or closing Ca2+ channels.
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PMID:Galanin--a neuropeptide with inhibitory actions. 871 35

Interest in 5-S-cysteinyldopa (5-S-CD), a major excretion product of normal and malignant melanocytes, has traditionally concentrated on its significance as a biosynthetic precursor of pheomelanins, the characteristic pigments of red hair, and as a specific biochemical marker for monitoring melanoma progression. The present study shows that 5-S-CD is a potent inhibitor of hydroxylation/oxidation reactions mediated by hydrogen peroxide and the Fe2+/EDTA complex under both aerobic and anaerobic conditions. The inhibitory effect of 5-S-CD, as determined by the deoxyribose and salicylic acid assays in phosphate buffer (pH 7.4), is much stronger than that of dopa, acetylsalicylic acid and mannitol, increases with increasing ligand-to-metal ratio, and is inversely proportional to the concentration of EDTA present in the Fenton system. Spectrophotometric evidence and competition experiments indicate that 5-S-CD forms a chelate complex with ferric ions (lambda max = 500 nm at pH 7.4), which may account for both an altered production of hydroxyl radicals by the Fenton reagent and a site-specific localization of oxidative damage on the chelate complex itself.
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PMID:5-S-cysteinyldopa, a diffusible product of melanocyte activity, is an efficient inhibitor of hydroxylation/oxidation reactions induced by the Fenton system. 878 28


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