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)

L-Dopa has has been shown to demonstrate enhanced toxicity toward melanoma cells in vitro. Since melanocytes arise from the neural crest embryologically, the effect of L-dopa methyl ester, a soluble analog, on the murine C1300 neuroblastoma was studied. There was significant antitumor activity against the neuroblastoma, which was enhanced by combination with a dopa decarboxylase inhibitor, Ro4-4602. In vitro studies suggested inhibition of DNA synthesis as the principal site of action. A mechanism involving sulfhydryl compound scavenging is postulated.
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PMID:L-Dopa methyl ester: prolongation of survival of neuroblastoma-bearing mice after treatment. 62 65

The incorporation of precursors of the biopigment melanin into melanotic and amelanotic S-91 Cloudman melanoma, mouse fibroblast L-929, and Chinese hamster ovary cells was studied. Tyrosine did not selectively accumulate in pigmented cells compared to that in nonpigmented control cells. Inhibition of protein synthesis with cycloheximide provided an estimate of the partition of tyrosine between protein (95%) and pigment biosynthesis (5%). L-3,4-Dihydroxyphenylalanine, a more proximal precursor of melanin, was selectively incorporated into pigmented cells up to 60 times that of control lines. alpha-Melanocyte-stimulating hormone and theophylline, agents that enhance pigmentation, further increased the incorporation of L-3,4-dihydroxyphenylalanine into melanocytic cells. A unique property of melanoma cells thereby has been defined that may permit a selective chemotherapeutic and diagnostic approach.
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PMID:Selective incorporation of L-3,4-dihydroxyphenylalanine by S-91 Cloudman melanoma in vitro. 86 38

By using ion-exchange column chromatography with effluent monitoring using the stable, free radical alpha,alpha-diphenyl-beta-picryhydrazyl as a colorimetric reagent, we have demonstrated the occurrence of elevated levels of five peaks in the urine of patients with metastatic disease. The tentative assignment of two of the peaks as 3,4-dihydroxyphenylalanine and as 3-methoxy-4-hydroxyphenylalanine has been made. Three remain unknown. The correlation of these peaks with the clinical status of melanoma patients shows that, while the individual excretion pattern of these compounds may be variable, the sustained occurrence of one or more of them in a patient's urine is evidence of recurrent or continuing disease. The excretion levels appear to be proportional to the tumor burden. The results with a group of 39 melanoma patientshaving Stage II or Stage III disease indicate that this chromatography technique provides earlier evidenc eof liver metastases than doses the liver scan, may detect occult metastases generally, and has detected tumor in clinically enlarged lymph nodes. This method, in its present form, does not detect small pulmonary lesions earlier than chest X-ray or tomography do or brain metastases earlier than do brain scan or computerized axial tomography. The technique is clinically useful for the diagnosis of melanoma patients and in their follow-up while under treatment.
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PMID:Detection of occult metastatic melanoma by urine chromatography. 97 93

Junction nevus, dermal nevus, melanosis circumscripta praecancerosa Dubreuilh, superficial spreading melanoma, and nodular melanoma were investigated and characterized by use of the formalin induced fluorescence method (FIF). In the vicinity of junctional nevus cell clusters and near tumor cells of the superficial spreading melanoma increased numbers of melanocytes are found. These show different types of dendritic branching. Spherical nevus cells however are completely devoid of dendritic processes. On the other hand, the atypical pigment cells in melanosis circumscripta praecancerosa Dubreuilh exhibit a shape similar to that of melanocytes, whereas the globular cells of superficial spreading melanoma have the appearance of nevus cells. The arrangement of nodular melanoma cells resembles that observed in dermal nevus. However the characteristic decrease in fluorescence intensity from epidermal junction to deeper dermis as observed in the dermal nevus was missed in nodular melanomas. Dendritic pigment cells displaying formalin induced fluorescence (FIF) could be demonstrated in all types of malignant melanomas investigated in the present study. The fluorophores of the pigment lesions are characterized microspectrofluorimetrically by (1) ill-defined emission maxima between 470 and 490 nm and (2) a clear-cut excitation maximum at 430 nm accompanied by a lower one at 320 nm. Hydrochloric acid vapor induces a hyposochromic shift of the 430 nm excitation maximum to 370-380 nm and a marked elevation of the 320 nm maximum. These results indicate fluorophores of DOPA and its derivatives; in this respect there are no marked differences between melanocytes, nevus cells and the cells of malignant melanoma.
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PMID:[Fluorescence histochemical and microfluorometrical investigations of pigmentary tumors of the skin (author's transl)]. 119 Aug 35

L-DOPA had no effect on the endogenous phosphorylation of proteins after extraction with 1% Triton X-100 from hamster melanoma. When proteins were purified further by wheat germ-agglutinin chromatography, however, a dramatic and dose-dependent inhibitory effect of DOPA on glycoprotein phosphorylation was observed in the presence of Mn+2.
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PMID:L-dopa inhibits in vitro phosphorylation of melanoma glycoproteins. 149 74

L-DOPA, the product of enzymatic hydroxylation of L-tyrosine, is released by melanotic melanoma cells in vivo and in vitro. Here we report that DOPA at pharmacologically relevant micromolar doses dramatically inhibits the stimulation of DNA synthesis by lipopolysaccharide and concanavalin A in murine splenocytes and human lymphocytes, having little or no effect on unstimulated (control) lymphocytes or proliferating fibroblasts. Therefore we propose that melanogenically active melanoma cells can inhibit the host's immune response via the release of DOPA and/or its oxidation products.
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PMID:Dopa inhibits induced proliferative activity of murine and human lymphocytes. 162 34

Cutaneous malignant melanoma of Sinclair Swine (SSCM) is a heritable, congenital neoplasm which either proves fatal to the neonatal animal or undergoes spontaneous regression. Four SSCM cell lines, UISO-SSCM-433, UISO-SSCM-438, UISO-SSCM-5052, and UISO-SSCM-8093, were derived from biopsy specimens of primary tumors removed from swine at 26, 8, and 8 weeks of age, and 15 weeks gestation, respectively. Morphologic features, DOPA oxidase staining, and abnormal karyotype were suggestive of malignant melanoma. Each cell line was morphologically heterogeneous in culture with dendritic, spindle- and cuboidal-shaped cells. Pigmented melanosomes and DOPA oxidase activity were present in all cell lines at passages 20-22. UISO-SSCM-433 and UISO-SSCM-5052 contained hypodiploid and hypotetraploid sublines whereas UISO-SSCM-438 and UISO-SSCM-8093 were hypodiploid and hypotetraploid, respectively. At later passages, all cell lines presented evolutionary, karyotypic changes; the same chromosomes were involved in the alterations, however. Chromosomes 2, 6, 13, and 14 were the most affected, exhibiting numerical and structural alterations in all four cell lines. Despite the presence of multiple chromosomal anomalies in all cell lines, each with a unique set of chromosomal markers, clonal growth was not detected in soft agar, nor were any of the lines tumorigenic following s.c. inoculation in athymic mice. This suggests that the loss of malignant potential in SSCM may be inherent.
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PMID:Establishment and characterization of four Sinclair swine cutaneous malignant melanoma cell lines. 163 85

The effect of DOPA and glutathione (GSH) on enzyme systems for 5-S-cysteinyl-DOPA (5SCD) genesis in murine melanoma cells cultured in tyrosine- and cystine-free medium were studied. DOPA at its optimum concentration (10(-5) M) when added alone did not alter tyrosinase, glutathione-S-transferase or gamma-glutamyl transpeptidase activities. In the presence of GSH at its optimum concentration (10(-5) M), DOPA loading did not cause any significant changes in tyrosinase or glutathione-S-transferase (GST) activities. This indicates that the higher 5SCD levels observed in the medium because of DOPA loading in the GSH dependent system results from increased substrate availability rather than the increased enzyme activity. An acute drop in 5SCD at DOPA concentrations above 10(-5) M observed in the GSH dependent system may be due to the inhibition of tyrosinase at high substrate concentrations (10(-4) M). Conversely, in the presence of DOPA, when GSH was increased, the resultant higher production of 5SCD could be explained by the increased activity of GST. When added alone, GSH (10(-5) M) caused a significant increase in GST (approximately 125%) and gamma-GTP (approximately 50%) activities. A drop in 5SCD in the medium when GSH was added beyond its optimum concentration (10(-5) M) in the DOPA-dependent system could be due to competitive inhibition of gamma-GTP by GSH. The data demonstrate that 5SCD genesis may be enhanced due to the accumulation of cytotoxic melanin precursors such as DOPA/DOPA quinone. The relative quantities of GSH at the sites of DOPA quinone formation and the levels of its metabolising enzymes can influence the type of product formed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of dopa-loading on glutathione metabolising enzymes and tyrosinase in relation to 5-S-cysteinyl-dopa genesis in cultured B-16 melanoma cells. 168 90

Retinoic acid, hexamethylene bisacetamide, sodium butyrate, and dimethylsulfoxide, four compounds which modulate phenotypic expression in a variety of neoplastic cell lines, all inhibited the induction of tyrosinase activity and melanogenesis by the combination of melanocyte-stimulating hormone and isobutylmethyxanthine in Cloudman S91 melanoma cells. Results were the same in assays of whole cells or in extracts made from them. Only retinoic acid, however, was effective at inhibiting the activation of dopachrome isomerase, another regulatory enzyme in melanogenesis. Despite inhibiting the effects of melanocyte-stimulating hormone (MSH) and isobutylmethylxanthine on tyrosinase activity, all of the agents tested increased the binding of MSH to intact cells. Ultrastructural analysis of treated cells following DOPA cytochemistry revealed that both retinoic acid and hexamethylene bisacetamide arrested melanosomal maturation at stage I-II. Retinoic acid resulted in a derangement of melanosomal structure. The specificity of these agents for preventing the induction of melanogenesis makes them powerful tools for the dissection of this complex cellular process.
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PMID:Inhibition of induced melanogenesis in Cloudman melanoma cells by four phenotypic modifiers. 170 21

Tyrosinase is a key enzyme in melanine biosynthesis. The modulating effect of cytostatic agents on DOPA-oxidase activity of tyrosinase could be linked with the drug treatment of melanoma tumors. Two groups of nitrosoureas which influence DOPA-oxidase activity of tyrosinase were studied: new nitrosoureas and their spin-labeled derivatives synthesized in our laboratory. Using Burnett's spectrophotometric method (Burnett et al., 1967) the following effects were established: inhibition by CCNU, inhibition and the activating effects of the other investigated nitrosoureas depend on their physicochemical half-life. The predominant activating effect of the spin-labeled derivatives is due to the nitroxyl radical present in these compounds.
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PMID:New nitrosoureas and their spin-labeled derivatives influence dopa-oxidase activity of tyrosinase. 176 6


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