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)

A number of biochemical aspects of melanogenesis were studied in 15 variously melanized human melanomas. The tryosinase activity was correlated with the degree of melanoma varied from 3,667 to 46,183 tryosinase units, in partially melanotic melanoma it varied from 14 to 75 tryrosinase units. The subcellular distribution of tryrosinase activity was limited to the particulate fraction )144,000 x g) of the partially melanotic and amelanotic melanomas. However, the melanotic melanomas contained the enzyme in both particulate and soluble fractions, with the greater tyrosinase activity in the particulate fraction. Electrophoretic resolution of tyrosinase isozymes in the soluble fraction or lipase-solubilized tyrosinase derived from the particulate fraction revealed three isozymes in melanotic melanomas. The isozyme of intermediate mobility always was the dominant form. In partially melaotic melanomas, the solubilized tyrosinase showed six isozymes. Three were similar to those of melanotic melanomas. The remaining three isozymes showed slower mobilities, possibly with greater molecular weights than the isozymes derived from melanotic melanomas. Inhibitors of tyrosinase were present in melanomas. Increased tyrosinase activity occurred after storing the homogenate at 0-4degree, removing of supernatant from the homogenate sediment, and washing the 144,000 x g particulate fraction, which suggested the presence of water-soluble, loosely bound inhibitor (s) in the soluble fraction of partially melanotic melanoma. Another inhibitor was released from the 144,000 x g particulate fraction of melanotic melanoma after lipase digestion. These substances inhibit both the isolated dominant tyrosinase isozyme(human) and mushroom tyrosinase. As inhibition of tyrosinase activity may produce regression of abnormal cell growth, the inhibitors may provide an approach to melanoma chemotherapy.
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PMID:Melanogenesis in human melanomas. 80 70

The melanogenic activity of tyrosinase as a function of temperature was studied in 9 different skin and melanoma tissues of vertebrates. The 600 times g supernatant fraction of tissue homogenates was incubated with 14C-L-tyrosine at 0 degrees to 60 degrees C for 16 hr and the 14C-melanin product was determined. The range of optimal temperature occurred at 35 degrees to 45 degrees C. The maximal activity and thermostability depended on the source of the enzyme preparation utilized. Thermal activation and species differences in the optimal temperature for maximal activity are complicated processes which depend upon many factors. At cold conditions, a higher percentage of maximal activity was achieved with enzyme from cold-blooded species than with enzyme from warm-blooded species.
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PMID:Thermal activation and inactivation of melanin formation in vertebrate skins and melanomas. 80 28

The possibility that peroxidase is functional in melanogenesis in the murine S-91 melanoma has been investigated. It was found that, as in the normal mouse, tyrosinase is the enzyme responsible for the bulk of melanin formation in the malignant melanocyte. Tyrosinase was capable of utilizing tyrosine as a substrate, as well as dopa, although the Vmax with dopa was much higher than with tyrosine. Conversely, the affinity of the enzyme for tyrosine is higher than for dopa, and this relationship may in part be responsible for the occasional misinterpretation of the functional capability of this enzyme.
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PMID:Involvement of tyrosinase in melanin formation in murine melanoma. 80 29

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

We have studied the kinetics of suppression of tyrosinase activity and tumorigenicity in unsynchronized B16 mouse melanoma cells (clone B559) exposed to 5-bromodeoxyuridine (BrdU, 3 mug/ml) for one or two cell divisions, then cultured in BrdU-free medium (RM) for five or six days. Bromouracil replaced about 23% of thymine residues after 24 hours (1 cell division) and almost 40% after 48 hours (2 cell divisions) in the presence of BrdU. Upon subsequent growth in RM the extent of replacement declined in a manner consistent with dilution by new DNA synthesis, reaching 5-10% substitution by day 7 of these experiments. Tyrosinase activity was significantly reduced after treatment with BrdU for 24 or 48 hours but continued to decline after the cultures were changed to RM, approaching undetectable levels on day 7. The time course of reduction was similar to that previously determined in cells grown continuously for seven days in the presence of BrdU. Therefore, suppression of tyrosinase activity can result from incorporation of BrdU during a single cell cycle, but requires about seven days for full manifestation of the effect. Tumorigenicity decreased to 55% after 24 hours and to 15% after 48 hours with BrdU but rapidly reversed to approach that of untreated melanoma cells when subsequently grown in RM for 5-6 days. The effects of BrdU on total RNA or protein synthesis, or on plating efficiency appeared insufficient to account for the degree of suppression observed. Our results indicate that substitution by bromouracil into either strand of DNA loci controlling tyrosinase activity or tumorigenic potential may be sufficient for suppression. In addition, they demonstrate that such brief treatment with BrdU may be used to probe the regulation of differentiated function and tumorigenicity in these melanoma cells.
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PMID:Suppression of melanoma cell tyrosinase activity and tumorigenicity after incorporation of bromouracil for one or two cell divisions. 81 76

The T1 variety of tyrosinase is present in both particulate and soluble or readily solubilized forms in the pigmented hypodermis (hair bulbs) of C57BL mice and Harding-Passey mouse melanoma. Trypsin treatment of 35,000g supernatants containing the microsomal (small granule) fraction of gentle homogenates of hair bulbs and melanoma results in significantly increased T1 activity within polyacrylamide gels. Similar treatment of 100,000g supernatants results in a slight increase in T1 activity. Addition of Triton-X or DOC to 35,000g supernatants of hair bulb and melanoma homogenates followed by centrifugation at 100,000g results in a marked enhancement of T1 when the latter supernatants are treated with trypsin. In the absence of trypsin treatment, T1 activity is comparable to nondetergent-treated controls. A slow-moving dopa-reactive band (Ts) is found in electropherograms of the nontrypsinized 100,000g supernants of detergent-treated 35,000g supernatants. It is absent in those treated with trypsin. The slow-moving enzyme appears to give rise to T1 molecules when eluted from acrylamide gels and even to a greater extent when elution is combined with trypsin treatment prior to reelectrophoresis. In mammals, tyrosinase apparently is not derived by a proteolytic activation of protyrosinase.
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PMID:Action of trypsin and detergents on tyrosinase of normal and malignant melanocytes. 81 38

The biochemistry of malignant melanoma is reviewed. The biosynthesis of melanin from tyrosine is described and the role of tyrosinase and other enzymes in melanoma considered. Detailed methods for the assay of free catechols, their metabolites and urinary indole melanogens are included. Normal values for these constituents and their significance in the evaluation of melanoma patients are discussed.
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PMID:Biochemistry of malignant melanoma. 81 57

Electrophoretic studies on malignant melanoma extracts before and after treatment with neuraminidase revealed that tyrosinase is a glycoprotein containing N-acetyl-neuraminic acid. Double diffusion tests using Concanavalin A and the lectin from Ricinus communis show that the carbohydrated chain of tyrosinase contains D-mannose as a sugar unit located within the carbohydrate chain. The terminal neuraminic acid groups are linked to D-galactose. The enzymatic activity of tyrosinase is not inhibited by Concanavalin A.
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PMID:Demonstration of carbohydrate structures in malignant melanoma tyrosinase. 81 68

Theophylline, a phosphodiesterase inhibitor, was found to be a potent stimulator of melanogenesis in the RPMI 3460 hamster melanoma cell line. This stimulation was greater than that caused by either dibutyryl cyclic AMP (db-cAMP) or another phosphodiesterase inhibitor, papaverine. Theophylline and db-cAMP treatments also produced strikingly different morphologies in the monolayered cells. The theophylline effect on melanogenesis was diminished by db-cAMP, whereas simultaneous treatment of cells with db-cAMP and papaverine produced greater stimulation of melanotic activity than either agent acting alone. Theophylline, therefore, may have phenotypic effects that are at least partially independent of phosphodiesterase inhibition. Theophylline stimulated melanin biosynthesis, as measured by rates of 2-[2-14C] thiouracil incorporation, and also caused an increase in the level of tyrosinase (EC 1.10.3.1) activity. This melanotic stimulation was prevented by the presence of cordycepin or cycloheximide. Theophylline inhibited DNA synthesis and mitosis in the melanoma cell cultures but stimulated protein synthesis. However, inhibition of proliferation and the first appearance of induced melanotic activity did not bear an immediate direct relationship to one another.
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PMID:Stimulation of melanotic expression in a melanoma cell line by theophylline. 81 64

Human tyrosinase, partially purified from metastatic malignant melanoma, reacted with antiserum prepared against tyrosinase purified from Harding-Passey mouse melanoma melanosomes, although the human and mouse tyrosinases were not completely identical immunologically. The human tyrosinae showed only one band on disc electrophoresis which corresponded in mobility to T2 tyrosinase of mouse.
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PMID:Immunologic cross-reaction between human and mouse tyrosinases. 81 20


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