Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical case of a 73-years old male who was admitted for diarrhea and loss of weight is presented. Barium enema and colonoscopy demonstrated small size polyps in the sigmoid colon, one of which had a histologic diagnosis of adenocarcinoma. Abdominal examination detected a mass in the mesohypogastrium which did not appear to be related to the previous findings. CAT and intestinal transit confirmed a second tumor in the small bowel with the histologic diagnosis of a resected specimen being melanoma.
 ...
PMID:[Melanoma of the small intestine and adenocarcinoma of the colon]. 762 22

Non-premelanosomal melanogenic compartments and their melanogenesis-controlling functions have been further elucidated. In addition to enzymatic and nonenzymatic controlling factors, we have also been exploring the role of melanogenesis-related genes. Naturally occurring intrinsic melanogenic inhibitors, MW < 6,000(alpha), 6,000-30,000(beta), and > 30,000(gamma), having different modes of action, have been identified within melanoma cells. One of the alpha-type melanogenic inhibitors of isolated tyrosinase(Ty) nonsuppressive types, later identified as lactic acid, induces depigmentation of cultured B-16 cells by the reduction in Ty activity level due to the inhibition of its mRNA expression. The transfection of Ty cDNA, rather than nuclear DNA-binding master regulatory gene, can induce, within both Ty-deficient amelanotic melanoma cells and also within fibroblasts, melanin polymer formation. This multisequential step occurs not only by the induction of Ty synthesis but also by the induction of other regulatory proteins and factors such as dopachrome tautomerase, DHICA-oxidase, catalase, Ty-glycosylation in GERL, and Ty-transfer by coated vesicles to newly assigned melanogenic vacuoles in which not only eumelanin but also rather pronounced concomitant pheomelanin formation is seen. Investigation of melanin-producing vacuoles in transfected fibroblasts and reexamination of premelanosomes in pigment cells has revealed the following: 1) Melanosomes possess phagocytic ability; 2) melanosomes receive tyrosinase and hydrolases via coated vesicles from GERL; 3) melanosomes possess lysosome-associated membrane protein 1 (LAMP-1); 4) amelanotic melanoma contains lysosome-like vacuoles with myelin figures that acquire typical premelanosome structure after Ty-cDNA transfection. Thus it is proposed that melanosomes are specialized lysosomes in pigment cells. Coated vesicles synthesize melanin monomers such as DHICA and some DHI, and have a monomer-stabilizing system. Thus they can transport them in intact form with Ty to premelanosomes, which subsequently polymerize these monomers by the action of DHICA-oxidase and T3-Ty. Selective eradication and diagnosis of malignant melanoma using our 10B-dopa analogue has been successfully performed in human melanoma patients using combined thermal neutron irradiation for the former and positron emission CT for the latter.
 ...
PMID:Molecular and biological control of melanogenesis through tyrosinase genes and intrinsic and extrinsic regulatory factors. 776 45

We have reported previously that a factor with a molecular weight of 53,000 under SDS-polyacrylamide gel electrophoresis purified from human erythrocyte extracts promoted the growth of a wide variety of cell types from different species, including T cells, B cells, myeloid leukemia cells, melanoma cells, and mastocytoma cells, as well as normal and transformed fibroblast cells. In the present study, amino acid sequence analysis revealed that this factor has homology with human catalase. The purified factor exhibited catalase activity. Catalases derived from human erythrocytes, bovine liver, Aspergillus niger, and recombinant rat liver catalase are all able to promote the growth of cells. Antibody against human catalase absorbed both the growth-promoting activity and the enzyme activity of the purified factor. In addition, treatment of the factor with an irreversible enzyme inhibitor, aminotriazole, resulted in abrogation of both the growth-promoting activity and enzyme activity. These results indicate that the growth-promoting factor is catalase, and its activity is associated with the decomposition of hydrogen peroxide.
 ...
PMID:A human erythrocyte-derived growth-promoting factor with a wide target cell spectrum: identification as catalase. 788 69

The present study was carried out to examine the role of reactive oxygen species in mediating the melanogenic effects of UVR. B16 mouse melanoma cells responded to a single dose of UVR by showing increases in their melanin content. Although there was a small increase in melanin at 48-72 hours, which was associated with a rise in tyrosinase activity at 48 h, the greatest change occurred at 3 h and this was not associated with an increase in tyrosinase activity. This short-term response, unlike the more delayed melanogenic response, was reduced by superoxide dismutase (SOD). Xanthine oxidase (XO), which generates the superoxide anion (O2-), also increased the melanin content of B16 melanoma cells with effects at 3 h and 48 h. As with UVR, the delayed response was accompanied by an increase in tyrosinase activity but no such association was evident at 3 h. In addition, the short-term effect, like that seen with UVR, was reduced with SOD and to a lesser extent with catalase. In contrast to the effects found with XO, glucose oxidase, which generates hydrogen peroxide, had no effect on the melanin content or tyrosinase activity of the B16 cells. These results confirm previous observations that UVR is able to act directly on cells to bring about delayed increases in melanogenesis. They further demonstrate that UVR also stimulates melanogenesis through a more rapid action that is not associated with an activation of tyrosinase. This effect could be mediated by the O2- which, rather than activating tyrosinase, could act by serving as a substrate for the enzyme.
 ...
PMID:The superoxide anion may mediate short- but not long-term effects of ultraviolet radiation on melanogenesis. 795 23

The potential cytotoxicity of the melanogenic intermediates DOPA, (L-3,4-dihydroxyphenylalanine) and DHI (5,6-dihydroxyindole) has long been recognized and exploited as a targeting concept in experimental melanoma therapy. In recent years, however, a novel branchpoint in the melanin biosynthetic pathway has been shown to divert the metabolism of DOPAchrome to a carboxylated derivative termed DHICA (DHI-2-carboxylic acid) rather than to DHI. In order to evaluate the biological implications of this regulatory control, we have reexamined the inherent cytotoxicity of DHICA versus DHI on different cell lines. We found that under the usual conditions of the biological assay, the apparent cytotoxicity of the two indoles reflect their instability in the culture medium, the less stable DHI being generally more toxic than DHICA to melanoma cells and nonmelanocytic cells. Moreover, the observed cytotoxic effects increased with the time of incubation and were markedly reduced by the addition of catalase to the medium, suggesting that they were probably due to the generation of reactive oxygen species (particularly H2O2) during the autoxidation of the melanin precursors outside the cells. To circumvent this problem, we then tested the diacetylated derivatives of DHI and DHICA (DAI and DAICA) which are sufficiently stable until taken up into the cells whereupon they may be converted by endogenous esterases back to the parent indoles. Although DAI proved to be cytotoxic for nonmelanocytic cells, it had no detectable activity on melanoma cells, whereas DAICA showed no effect on any of the cells examined. These results, when combined with other studies, point to a reconsideration of the inherent cytotoxicity of the 5,6-dihydroxyindoles, as well as DOPA, to melanin producing cells.
 ...
PMID:The inherent cytotoxicity of melanin precursors: a revision. 816 48

Low plasma selenium levels have been linked to increased risk of non-melanoma skin cancer in humans. The present study examined the relationship between selenium level in the diet and development of skin tumors induced by ultraviolet radiation in female Skh:HR-1 hairless mice. Animals were maintained on a torula yeast-based diet containing either 0, 0.1, or 0.5 mg/kg selenium as Na2SeO3. Ultraviolet light at a dose of 90 mJ/cm2, three times weekly for 20 weeks, resulted in skin tumors in all groups. Following cessation of ultraviolet light exposure, tumors continued to increase in selenium-deficient mice and those fed only 0.1 mg/kg, but leveled off for those on 0.5 mg/kg. During the carcinogenesis process, epidermal antioxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase were monitored. Selenium deficiency decreased glutathione peroxidase and resulted in an early increase in superoxide dismutase and catalase in response to ultraviolet light treatment. These results indicate that dietary Se may be an important chemopreventive agent for skin cancer.
 ...
PMID:Effects of dietary selenium on UVB-induced skin carcinogenesis and epidermal antioxidant status. 817 60

Many genes mapping to pigmentation loci are involved in the regulation of melanin synthesis in the mouse. The brown (b) locus controls black/brown coat coloration, and its product has significant homology to the key melanogenic enzyme tyrosinase. This has led to suggestions that the b-protein is itself a melanogenic enzyme. In order to investigate its function, we have established lines of mouse fibroblasts stably expressing the b-protein by co-transfection of a b-protein expression vector and a plasmid conferring resistance to the antibiotic G418. The b-protein synthesised by these cells has the expected molecular mass of 75 kDa and reacts with three different anti-b-protein antibodies. We were unable to confirm previous reports that the b-protein has tyrosinase or catalase activity, but detected stereospecific dopachrome tautomerase activity in b-protein-expressing fibroblasts. This dopachrome tautomerase binds to Concanavalin A-Sepharose, and the major product of its action on L-dopachrome is 5,6-dihydroxyindole-2-carboxylic acid. Since this activity is not present in untransfected cells we conclude that the b-protein has dopachrome tautomerase activity. Fibroblasts do not contain melanosomes, the specialised organelles in which the b-protein is located in melanocytes. Nevertheless, indirect immunofluorescence localisation of the b-protein in transfected fibroblasts produces a distinctive pattern of intense juxtanuclear staining combined with punctate cytoplasmic staining. Double-labelling shows co-localisation of the b-protein with the late endosomal/lysosomal markers beta-glucuronidase and LAMP-1, both in transfected fibroblasts and in mouse melanoma cells. These findings are consistent with the hypothesis that melanosomes are closely related to lysosomes.
 ...
PMID:The mouse brown (b) locus protein has dopachrome tautomerase activity and is located in lysosomes in transfected fibroblasts. 827 Jun 21

The protective role of melanin, either synthetic or derived from a metastatic lung melanoma nodule, was studied in terms of its ability to interact with active oxygen species (O2., H2O2, RO., ROO., etc.). Both melanins showed the ability to react with O2.. The superoxide dismutase-like activity corresponds to 21 and 10 U/mg for synthetic and tumor melanin, respectively. The latter value accounts for about 8% of the superoxide dismutase activity of cultured melanoma cells. Neither type of melanin showed catalase-like or glutathione peroxidase-like activity. Both types of melanin reacted with RO. and ROO. radicals as determined by inhibition of the lipid peroxidation reaction of rat liver homogenates. The spontaneous lipid peroxidation of rat liver homogenate was inhibited up to 90% and 80% by synthetic and tumor melanin with half-maximal effects at 2.5 and 5.5 micrograms melanin/ml, respectively. The 2,2-azo-bis-(2 amidino propane) (AAPH)-initiated lipid peroxidation of rat liver homogenate was inhibited up to 30% and 20% by synthetic and tumor melanin, with half maximal effect at 120 and 500 micrograms melanin/ml, respectively. Both types of melanin were able to protect the in vitro inactivation of glucose oxidase, which occurs in the presence of AAPH-generated radicals.
 ...
PMID:Role of melanin as a scavenger of active oxygen species. 830 73

The activities of reactive oxygen species scavenging enzymes, superoxide dismutases (SODs) and catalase (in cells of two melanomas (mouse B16 and human SK23) and in Chinese hamster ovary (CHO) cells were examined. Melanoma cells are relatively depleted in activities of superoxide dismutases and catalase as compared to CHO cells. Short equitoxic (500 microM for CHO and B16 cells and 5 microM for SK23 cells) paraquat treatment (15 min before the X-irradiation, 45 min in postirradiation period--the total time of treatment was 1 h) caused an increase in radiation resistance, measured as colony forming ability, in two of the three lines examined. It is proposed that PQ may exert its radioprotective effect by induction of antioxidant enzymes.
 ...
PMID:The effect of paraquat on the radiosensitivity of melanoma cells: the role of superoxide dismutase & catalase. 831 24

The effects of systems generating active oxygen species (superoxide anion, hydrogen peroxide, hydroxyl radical) on tyrosinase have been studied in cultured human melanoma cells. Tyrosinase activity was determined by measuring the quantity of 5-S-L-cysteinyl-L-dopa (5-S-CD) formed in the presence of D,L-dopa and L-cysteine. In some experiments, the enzyme protein was determined by radio immunoassay [RIA]. Exposure of cells to xanthine/xanthine oxidase or glucose/glucose oxidase resulted in a dose-related elevation of tyrosinase. Catalase, but not superoxide dismutase, prevented this increase indicating that hydrogen peroxide may be the agent responsible for the action, whereas superoxide anion is not involved. Hydroxyl radicals formed by the Haber-Weiss or Fenton type reactions were not found to produce elevation of tyrosinase. Catalase determinations showed no enzyme in the medium but a high concentration in the cells. Inhibition of intracellular catalase by 3-amino-1,2,4-triazole caused an increase in the tyrosinase level. The effects of dopac, xanthine/xanthine oxidase, and glucose/glucose oxidase all producing hydrogen peroxide, and increasing tyrosinase, were enhanced by the inhibition of catalase. It is concluded that hydrogen peroxide, formed by the systems, accounts for the elevation of tyrosinase level. When tyrosinase activities determined by 5-S-CD formation were compared to enzyme amounts found by RIA, the ratios of these values were always constant. This fact indicates that the increase in the tyrosinase activities was not due to an activation of the enzyme, but mirrored the quantities of enzyme protein present in the samples. On the basis of our findings, it is assumed that hydrogen peroxide is a regulator of tyrosinase in normal melanocytes and melanoma cells.
 ...
PMID:Hydrogen peroxide as an inducer of elevated tyrosinase level in melanoma cells. 843 9


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>