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)

Cultured melanoma cells were labeled with 3H-leucine over a period of 1-3 days. The labeled cells were mechanically disrupted and a preparation of "extranuclear membranes" was obtained by differential centrifugation. The membrane fragments were solubilized by the nonionic detergent NP-40 and the soluble material was double precipitated with antisera from melanoma patients and anti-human immunoglobulin sera. Because of the small quantitative differences of precipitated radiolabeled material between control and melanoma patients' sera, the precipitates were further analyzed on SDS-containing polyacrylamide gels. The labeled profiles of experimental and control gels now revealed clearcut differences usually seen in 2-3 characteristic peaks in the molecular weight range from 130,000-330,000.
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PMID:Membrane associated antigens of human malignant melanoma. I. Internal labeling, detergent solubilization and characterization by homologous antisera and polyacrylamide gel electrophoresis. 12 75

Serum removal from the media of serial monolayer cultures of the Harding-Passey melanoma during an incubation period of 3 days resulted in an exponentially declining DNA synthesis rate (measured by the incorporation of [14C]thymidine) and in an inhibition of cell proliferation. Protein synthesis, as measured by the incorporation of radioactive leucine, was less affected than DNA synthesis. Incubation in serum-free culture medium resulted in significant rises of tyrosinase activity and cellular melanin content. Addition of dibutyryl adenosine 3':5' monophosphate (Bu2cAMP, 5X10(-4) M) and theophylline (5X10(-4) M) to serum-free cultures caused a further striking increase of tyrosinase activity and melanin formation, while treatment of serum containing cultures with Bu2cAMP and theophylline showed only a slight rise in melanogenesis. It is suggested that these stimulatory effects are mediated by an increased intracellular cAMP level, since a correlation between the degree of melanogenesis and cellular cAMP content was indicated. Treatment of serum-free or serum-containing cultures with the phosphodiesterase inhibitor theophylline (5X10(-4)--10(-3)M) alone revealed only a slight enhancement (about 20%) of melanogenesis. Because augmentation of melanogenesis by serum-free medium alone or together with Bu2cAMP and theophylline was prevented by cycloheximide (or actinomycin D), de novo protein synthesis seems to be required for these stimulatory effects.
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PMID:Stimulation of tyrosinase activity and melanin formation of cultured melanoma cells by serum deprivation alone or in combination with dibutyryl cyclic AMP and theophylline. 19 88

3,4-Dihydroxybenzylamine (DHBA), a dopamine analog, was much less toxic than dopamine when tested against the B16 melanoma in vivo and in vitro. Daily doses of 1,000 mg DHBA/kg were better tolerated than doses of 400 mg dopamine/kg. When tested against the B16 melanoma in (C57BL/6 x DBA/2)F1 mice, DHBA had a significantly improved therapeutic effect as shown by a life-span increased 70% as compared to 48% with dopamine. DHBA shared the catecholamine property of selectively inhibiting thymidine incorporation as compared to leucine or uridine incorporation. Because the inhibitory effects of DHBA on the B16 melanoma cells in vitro were similar to those of dopamine, much of the improved efficacy in vivo might be attributed to decreased toxicity.
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PMID:3,4-Dihydroxybenzylamine: a dopamine analog with enhanced antitumor activity against B16 melanoma. 29 14

Murine melanoma cells provide an excellent system for studying the proposed role of nuclear nonhistone proteins (NHP's) as regulators of gene expression. Cloudman mouse melanoma cells (S91, NCTC 3960, CCL 53), grown in culture, are normally lightly pigmented, but in the presence of melanocyte stimulating hormone (MSH) show a large increase in melanin content. Cells were grown in medium with and withoug MSH and labeled with either 14C- or 3H-leucine, respectively. Following 48 hr of incubation, the cells were harvested, combined, and nuclei isolated. The NHPs were extracted from these nuclei in a series of steps which yielded 4 major fractions. Each fraction was further separated on DEAE cellulose columns into a total of 40 subfractions, each of which was electrophoresed on SDS gels. Each gel was sliced and counted and the 14C/3H ratio was determined for each slice. A number of differences in 14C/3H ratios were observed between the NHPs isolated from MSH-treated and control cells which reflect changes in the synthesis and/or transport of NHPs in MSH-treated cells.
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PMID:Nuclear nonhistone proteins in murine melanoma cells: II. changes following exposure to MSH. 41 35

In seven human melanoma cell lines and one human fibroblast strain some correlation of resistance to cell killing was found with two bifunctional alkylating agents (melphalan, chlorambucil) and three monofunctional agents (4(5)-(3,3-dimethyl-l-triazeno)imidazole-5(4)-carboxamide (DTIC), methylmethane sulphonate (MMS) and N-methyl-N1-nitro-N-nitrosoguanidine (MNNG), but little cross-resistance was found between these two groups of agents or with cytosine arabinoside (ara-C). In contrast to previous studies with rodent tumours, potentially synergistic (chloroquine, arginine) or antagonistic (ascorbic acid, leucine) compounds did not affect the toxicity of melphalan in a human melanoma cell line. In two melanoma lines DTIC induced patterns of DNA damage (inhibition of semi-conservative synthesis) and repair (strand breaks and repair synthesis) similar to, but not identical with, those induced by the methylating agent MMNG. These results suggest that a methylating species is derived from DTIC but has a different reactivity toward DNA compared with MNNG.
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PMID:Cytotoxicity studies of human melanoma cells and fibroblasts. 48 82

Hamster melanoma cells (RPMI 3460) were examined for their ability to utilize phenylalanine for melanin biosynthesis. There was a small but significant incorporation of L-[1-1414C] phenylalanine into hot acid-insoluble cellular material in the presence of cycloheximide. However, this radioactivity was removable from the acid-insoluble fraction by pronase digestion. A similar percentage of L-[U-14C] leucine incorporation was likewise resistant to cycloheximide inhibition. Residual protein synthesis is apparently responsible for the incorporation of both amino acids. Cycloheximide did not inhibit melanin synthesis. These results suggest that mammalian melanocytes do not use phenylalanine for melanin synthesis. Phenylalanine is not incorporated directly into melanin, nor do the cells appear to convert it to tyrosine via a phenylalanine hydroxylase.
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PMID:Mammalian melanocytes do not use phenylalanine for melanin synthesis. 55 59

L-dopa methyl ester has been shown to be an effective antitumor agent against the B-16 melanoma in vivo. We have now examined the analog, dopamine, a major catabolite of L-dopa. Dopamine administration at a daily dose of 600 mg/kg resulted in a 48% (p less than .001) increase in survival of treated mice as compared to non-treated controls. In vitro, an effect similar to that observed with L-dopa methyl ester was noted, specifically, a rapid and profound inhibition of thymidine incorporation with little effect on uridine or leucine incorporation. We have postulated that the inhibition of a DNA polymerase might be the site of action of these novel antitumor agents.
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PMID:Dopamine: a novel antitumor agent active against B-16 melanoma in vivo. 68 87

The effect of 4-isopropylcatechol (4-IPC), a potent, irreversible cutaneous depigmenting agent, on protein biosynthesis of malignant melanoma cells in mice was studied by examining the in vitro amino acid (leucine) incorporation into a microsome fraction in cell sap. The present study revealed that 4-IPC does not inhibit the protein biosynthesis of the cell-free system in mouse liver, but remarkably inhibits it in mouse melanoma cells, which contain a high level of tyrosinase. The enhanced inhibition was found also in the mouse liver cell-free system when tyrosinase was added. Air oxidation products of 4-IPC were not responsible for such inhibition. These results may indicate that 4-IPC directly inhibits protein biosynthesis, probably by some intermediates that occur in an early stage of enzymatic oxidation of 4-IPC.
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PMID:Tyrosinase-mediated inhibition of in vitro leucine incorporation into mouse melanoma by 4-isopropylcatechol. 81 Feb 42

Several agents were compared for their ability to inhibit protein synthesis for long periods in tumor cells growing in culture. Mouse B16 melanoma cells, treated with high concentrations of cycloheximide or pactamycin for 1 hour and then washed repeatedly, recovered their ability to incorporate [3H]leucine into protein in about 4 hours, while cells treated with emetine recovered in 12 hours. After similar treatment with muconomycin A, however, incorporation of [3H]leucine remained inhibited for at least 30 hours. During this time the cells remained attached to the culture dishes, were able to exclude trypan blue dye, and retained nearly normal levels of rubidium-86 content. When another, untreated, population of cells was added to the muconomycin-treated cells, protein synthesis was not inhibited in the untreated population; action of the drug was thus shown to be confined to the treated cells. In melanoma cells treated with neuraminidase and muconomycin, measurement of glycoprotein synthesis (as determined by sialic acid analysis) showed that muconomycin also inhibited restoration of sialic acid content. Brief treatment with muconomycin, therefore, appeared to be sufficient for prolonged inhibition of protein and glycoprotein synthesis.
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PMID:Prolonged inhibition of protein and glycoprotein synthesis in tumor cells treated with muconomycin A. 83 56

Lymphocyte-stimulated protein synthesis (SPS) in response to human tumor-associated antigens was assessed by measuring [3H]leucine incorporation. Correlation of SPS with other in vivo and in vitro response was demonstrated by immunizing normal subjects with keyhole limpet hemocyanin and testing sequentially frozen lymphocytes and serum samples. One week after immunization, lymphocytes from normal subjects demonstrated increased SPS to keyhole limpet hemocyanin. This correlated with the appearance of delayed cutaneous hypersensitivity responses and preceded detection of hemagglutinating antibodies and increases in lymphocyte [3H]thymidine incorporation. There was no difference in the reactivity of fresh and viable frozen lymphocytes, and as few as 5X 10(5) lymphocytes/microtiter plate well could be used. Tumor-associated antigens were prepared from four lung carcinomas, six sarcomas, and six melanomas, using 3 M KCI extraction. Lymphocyte responses to both autologous and allogeneic tumor extracts were observed. Five of 15 patients demonstrated significant SPS to autologous tumor antigens. Fourteen of 20 lung cancer patients responded to lung cancer antigen, whereas only 11 of 41 patients with other tumors and 3 of 19 normal subjects reacted. Significantly, more lung cancer patients reacted to the tumor extract than to an extract of uninvolved lung from the same patient. Twenty-one of 42 melanoma patients responded to melanoma antigen. Ten of 33 patients with other tumors and 3 of 24 normal subjects reacted to the melanoma extract. Eight of 30 melanoma patients reacted to an extract of muscle from the same donor as was the melanoma antigen. Tumor-associated antigenic activity of 3 M KCI extracts can therefore be detected by measuring lymphocyte [3h]leucine incorporation.
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PMID:A rapid assay for stimulation of human lymphocytes by tumor-associated antigens. 97 69


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