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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The response of human melanocytes and melanoma cells to hydrogen peroxide stress was measured. Cells were exposed to glucose/glucose oxidase or free H2O2 and reactive oxygen species measured by luminol-enhanced chemiluminescence. The response was distinctly different between the two types and the addition of superoxide dismutase to melanoma cells paradoxically enhanced the chemiluminescent signal. These findings coupled with other known differences between the way these two types of cells handle oxidative stress at a molecular level suggests that a therapeutic window may be available for exploitation.
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PMID:Luminol-enhanced chemiluminescent response of human melanocytes and melanoma cells to hydrogen peroxide stress. 926 7

Various investigations have reported the occurrence in bacterial and mammalian cells of an adaptive response to the toxic effects of oxidants or agents that cause oxidation via redox reactions. In our previous study, it was shown that several cell lines pretreated with a low dose of hydrogen peroxide (H2O2) exhibited an adaptive response to subsequent high doses of adriamycin (ADR), whereas other cell lines did not. Based on the observation that the cell lines utilized differed in their sensitivity towards adriamycin, we undertook the present investigation with the goal of evaluating possible relationships between the levels of antioxidant enzymes and sensitivity towards adriamycin. Another aim was to determine relationships between the inducibility of these enzymes and the occurrence of adaptation. We utilized African Green monkey kidney (V3), human embryo (CLV98), human melanoma (ME18), and Chinese hamster ovary (CHO) cell lines and experimentally developed adriamycin-resistant human melanoma (ME18/RN) and Chinese hamster ovary (CHO/RN) cell sublines. Cytotoxicity was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and trypan blue exclusion. The levels of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were determined in the same kind of experiment as that revealing the occurrence of adaptation. The rank order established for catalase activities was similar to that for sensitivity towards adriamycin. Aberrant increases in the tested enzymes were demonstrated in experimental groups of all kinds of cells. We conclude that in our cell systems catalase is a major determinant of adriamycin resistance. Whether the occurrence of the adaptive response under study is dependent on the contribution of catalase, itself dependent on the degree of resistance to the drug, is discussed.
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PMID:Studies on adaptation to adriamycin in cells pretreated with hydrogen peroxide. 933 76

Soluble intercellular adhesion molecule-1 (sICAM-1) and copper zinc superoxide dismutase (CuZnSOD) were measured in 930 serum samples of 256 patients with histologically proven malignant melanoma and 78 serum samples of 78 controls by enzyme-linked immunosorbent assay. Seventy-seven patients were stage Ia, 79 stage Ib, 59 stage IIa, 30 stage IIb, 13 stage IIIb, and 7 stage IV according to the German Society of Dermatology (DDG) classification. We calculated the normal range (mean +/- SD) for sICAM-1 (71.3-257.3 ng/ml; mean 163.3 ng/ml) and CuZnSOD (34.8-175.6 ng/ml, mean 105.2 ng/ml). The serum levels of sICAM-1 were significantly higher in all stages of melanoma than in controls (p<0.00005). Additionally, significant differences were observed between different stages of melanoma (Ia and Ib vs IIa/IIb/IIb/IV, IIa and b vs IV). The mean levels of sICAM-1 in melanoma were lowest in stage I (Ia: 257.25 ng/ ml, Ib: 252.47 ng/ml) and highest in stage IV (394.24 ng/ml). Significant differences in CuZnSOD levels were not detected between melanoma patients and controls, neither between melanoma patients of different stages. A decrease of CuZnSOD was found in only 37 samples of melanoma patients independent of the clinical stage. Our results demonstrate a relationship of increased sICAM-1 levels to melanoma and disease progression. We conclude that sICAM-1, but not CuZnSOD, is useful in monitoring of patients with malignant melanoma and might be beneficial in evaluation of therapeutic efficacy.
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PMID:Simultaneous measurement of circulating intercellular adhesion molecule-1 and serum copper zinc superoxide dismutase activity in patients with malignant melanoma. 946 82

In recent studies, decreased expression of Mn SOD, an intramitochondrial enzyme responsible for the dismutation of anion superoxide, has been reported in multiple, malignant cell types, whereas its gene has been proposed as a tumour suppressor gene in melanoma. We studied the expression of Mn SOD both at genetic (DNA, mRNA) and protein levels in three human melanoma cell lines (M3 Da, M4 Be, M1 Do). All cell lines were tumorigenic in a nude mouse model. In these cell lines, Mn SOD was studied at the molecular level using PCR of genomic DNA, and by RT-PCR of total mRNA extracts to detect Mn SOD transcripts. Mn SOD protein expression was studied by indirect immunofluorescence using a monoclonal antibody anti-human Mn SOD (Bender) on suspended cells fixed on slides after cytospin. All three human melanoma cell lines studied contained detectable amounts of DNA and mRNA specific for the Mn SOD gene. In contrast, there was variable expression of Mn SOD at the protein level. As detected by immunofluorescence, Mn SOD protein was expressed in only two cell lines (strongly in M3 Da, weakly in M4 Be) but not in M1 Do. These preliminary, qualitative results demonstrate that the deficit of Mn SOD protein expression is variable depending on the particular melanoma cell line. Further investigations are required in order to evaluate quantitative Mn SOD protein expression and activity as well as the level of functional Mn SOD mRNA and DNA in these or other cell lines.
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PMID:Variable expression of Mn SOD in three different human melanoma cell lines. 964 9

We have previously shown an imbalance of the antioxidant system in some cultures of normal melanocytes from patients with melanoma. In order to evaluate if the alteration of the antioxidants could be the basis of an increased sensitivity to exposure to peroxidative agents, in cultured melanocytes from normal individuals (n = 11) and from patients with melanoma (n = 11), superoxide dismutase and catalase activities were evaluated by spectrophotometer, and the levels of vitamin E and of the polyunsaturated fatty acid of cell membranes were determined by gas chromatography mass spectrometry. In 5 out of the 11 cultures of melanocytes from melanoma patients, with respect to those from normal individuals, a significant decrease of catalase activity (Cat) associated with an increase of vitamin E (Vit E) concentration was found, whereas no significant modification of superoxide dismutase activity (SOD) was observed. A wide range of variability was detected in the percentage of the polyunsaturated fatty acids of the cell membranes and a correlation was found between the ratio SOD/Cat and the percentage of linoleic acid, indicating that the imbalance of the enzymatic antioxidants leads to a lipoperoxidative process. The electron microscopic examination of these cultures revealed many microvilli in the plasma membranes and nuclear infoldings and in the cytoplasm light vacuoles. Moreover some cells contained several dense bodies with a round shape and numerous spherical lamellae possibly representing immature melanosomes. Treatment with cumene hydroperoxide between 0.66 and 20 microM did not produce a significant modification of cell viability in melanocytes from normal individuals. On the contrary in melanocytes from melanoma patients correlated with the ratio Vit E/Cat, considered as a parameter of the antioxidant imbalance, a stimulatory effect was observed at 0.66 microM CUH and a cytotoxic effect at 20 microM. In conclusion our results suggest that a constitutional alteration of the scavenger system could be present in normal melanocytes from melanoma patients and that this could be the basis for an increased sensitivity to pro-oxidant agents.
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PMID:Increased sensitivity to peroxidizing agents is correlated with an imbalance of antioxidants in normal melanocytes from melanoma patients. 975 19

Five human melanoma cell lines were investigated for their antioxidant activities. These metabolic data were correlated with cytogenetic analysis giving the relative numbers of chromosomes or chromosomal segments carrying the gene encoding for each enzyme. Particular attention was focused on the expression of superoxide dismutase 2 (SOD2), whose gene, located on the long arm of chromosome 6 (6q), has been proposed as a tumour suppressor gene. The activity of glutathione peroxidase (GPX), glutathione reductase (GSR) and catalase appeared to be unrelated to the relative number of 3q, 8p and 11p arms which, respectively, carry their encoding genes. GPX activity paralleled that of total SOD activity, and GSR variations followed those of GPX, suggesting possible metabolic regulation. Both the activity and the amount of SOD1 immunoreactive protein correlated with the number of chromosomes 21, suggesting a gene dosage effect. The three cell lines with deletions of the 6q arm had lower SOD2 activity and less immunoreactive protein than the two cell lines without 6q deletion. In addition, they demonstrated high thymidine kinase and thymidylate synthetase activities, which are directly linked to the cell proliferation rate. These results strengthen the hypothesis that SOD2 has a function as a tumour suppressor gene, but also suggest that the expression of other antioxidant enzymes might be altered in human melanomas.
Melanoma Res 1998 Aug
PMID:Modifications of the antioxidant enzymes in relation to chromosome imbalances in human melanoma cell lines. 976 8

Metastasis is a complicated multi-step process involving interactions between tumour cells, the extracellular matrix and the vessel walls. Experimental observations suggest that leucocyte migration and function could be a suitable model in order to understand tumour cell dissemination. In the present report we show and quantify the production of free radicals by human malignant melanoma cells (St-ml12) by means of a spectrophotometrical method, using an enzyme immunoassay reader. Endothelial cells and activated polymorphonuclear leucocytes were used as controls. Melanoma cells without stimulants produced large amounts of superoxide anion at an increasing rate in relation to time, which could be inhibited by superoxide dismutase. Production of hydrogen peroxide was minimal. The endothelial cells produced a negligible amount, in contrast to the activated polymorphonuclear leucocytes, which released large quantities of both free radicals. A rapid assay to analyse the production of free radicals by tumour cells is presented here. Using this, we demonstrated that melanoma cells produce superoxide anions, supporting previous observations which implicate superoxide anion in the mechanism of metastasis.
Melanoma Res 1998 Oct
PMID:Production of superoxide by human malignant melanoma cells. 983 50

Intracellular superoxide (O(2)*- was manipulated in M14 melanoma cells by overexpression or repression of Cu/Zn SOD using a tetracycline-inducible expression system. Scavenging intracellular O(2)*- increased tumor cell sensitivity to daunorubicin, etoposide, and pMC540, whereas expression of the antisense SOD mRNA significantly decreased cell sensitivity to drug treatment. Whereas Cu/Zn SOD overexpressing cells exhibited higher activation of the executioner caspase 3 upon drug exposure, caspase 3 activation was significantly lower when Cu/Zn SOD was repressed by antisense expression. These data show that intracellular O(2)*- regulates tumor cell response to drug-induced cell death via a direct or indirect effect on the caspase activation pathway.
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PMID:Superoxide anion inhibits drug-induced tumor cell death. 1052 62

The flavonoid antioxidant silymarin is used clinically in Europe and Asia for the treatment of liver diseases and is sold in the United States and Europe as a dietary supplement. Recently we showed that silymarin possesses exceptionally high cancer-preventive effects in different mouse skin carcinogenesis models and affords strong anticancer effects in human skin, cervical, prostate, and breast carcinoma cells. More recently, we showed that the anti-tumor-promoting effect of silymarin is primarily targeted against stage I tumor promotion in mouse skin (Cancer Res 1999;59:622-632). Based on this recent study, in this report, further investigations were made to identify and define the biochemical and molecular mechanisms of silymarin's effect during stage I tumor promotion in mouse skin. A single topical application of silymarin at 3-, 6-, and 9-mg doses onto SENCAR mouse skin followed 30 min later with 12-O-tetradecanoylphorbol 13-acetate (TPA) at a 3-microg dose resulted in a 76-95% inhibition (P < 0.001) of TPA-caused skin edema. Similarly, these doses of silymarin also showed 39-90%, 29-85%, and 15-67% protection (P < 0.05 or 0.001), against TPA-caused depletion of epidermal superoxide dismutase, catalase, and glutathione peroxidase activity, respectively. Pretreatment of mice with silymarin also produced highly significant inhibition of TPA-caused induction of epidermal lipid peroxidation (47-66% inhibition, P < 0.001) and myeloperoxidase activity (56-100% inhibition, P < 0.001). In additional studies assessing the effect of silymarin on arachidonic acid metabolism pathways involving lipoxygenase and cyclooxygenase (COX), similar doses of silymarin showed highly significant inhibition of TPA-caused induction of epidermal lipoxygenase (49-77% inhibition, P < 0.001) and COX (35-64% inhibition, P < 0.01 or 0.001) activity. Western immunoblot analysis showed that the observed effect of silymarin on COX activity was due to inhibition of TPA-inducible COX-2 with no change in constitutive COX-1 protein levels. In other studies, silymarin also showed dose-dependent inhibition of TPA-caused induction of epidermal interleukin 1alpha (IL-1alpha) protein (39-72% inhibition, P < 0.005 or 0.001) and mRNA expression. Taken together, the results from these biochemical and molecular studies further substantiate our recent observation of silymarin's anti-tumor-promoting effects primarily at stage I tumor promotion. Furthermore, the observed inhibitory effects of silymarin on COX-2 and IL-1alpha should be further explored to develop preventive strategies against those cancers in which these molecular targets play one of the causative roles, such as non-melanoma skin, colon, and breast cancers in humans.
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PMID:Significant inhibition by the flavonoid antioxidant silymarin against 12-O-tetradecanoylphorbol 13-acetate-caused modulation of antioxidant and inflammatory enzymes, and cyclooxygenase 2 and interleukin-1alpha expression in SENCAR mouse epidermis: implications in the prevention of stage I tumor promotion. 1056 9

It is well known that ICAM-1 expression can be stimulated by TNF and by oxidative stress, via the activation of specific transcription factors. Two of these--NFkappaB and AP-1--can also be activated by reactive oxygen species, including the superoxide anion (also produced under TNF challenge). The latter is inactivated by superoxide dismutase of which two forms exist: Cu/Zn-SOD (cytoplasmic) and Mn-SOD (mitochondrial). We investigated whether superoxide anion direct generation or accumulation through specific SOD inhibition, may affect ICAM-1 expression in human melanoma and endothelial cells. Our results show a 20-50% increase in both SOD activities when cells were exposed to TNF or to an oxidative stress produced by Paraquat (a generator of superoxide anion radicals), both in terms of enzymes activity (zymogram) and protein levels (Western blotting and ELISA). Either with TNF or Paraquat, we could measure a significant increase of ICAM-1 expression with maxima ranging from 140 to 200%, depending on the cell line. Specific inhibition of Cu/Zn-SOD activity by DTIC (diethyldithiocarbamic acid), in presence of Paraquat or TNF, was followed by an upregulation of ICAM-1 expression (60 and 20%, respectively). In contrast, the addition of a SOD mimetic (MnTMPyP) completely inhibited Paraquat-stimulated ICAM-1 expression in melanoma cells and significantly decreased it in HUVEC (50%). In presence of TNF however, the same SOD mimetic inhibited TNF-stimulated ICAM-1 expression by 25% in melanoma and 17% in endothelial cells. In conclusion, these data provide evidence that melanoma and endothelial cells exposure to TNF or oxidative stress results in a significant increase of both Mn- and Cu/Zn-SOD activities. This increase seems to be associated with a reduction in the stimulation of ICAM-1 expression by TNF or oxidative stress.
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PMID:SODs are involved in the regulation of ICAM-1 expression in human melanoma and endothelial cells. 1064 10


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