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)

Metallothioneins are ubiquitous proteins with a high affinity for heavy metal ions, e.g. zinc, copper and cadmium. Experimentally, metallothionein over-expression in cell lines derived from a variety of cancers has been associated with resistance to anticancer drugs and irradiation therapy. Using a monoclonal antibody (E9) to metallothionein we investigated immunoreactive expression in routinely fixed and paraffin-embedded tissue from 63 cases of malignant melanoma and 13 secondary deposits. Whereas a variety of cells in normal skin showed metallothionein expression, all forms of benign naevi studied were uniformly negative. In contrast 13/30 'thin' (< or = 1.5 mm; 0.7 +/- 0.4), 25/29 'thick' malignant melanoma (> 1.5 mm; 5.5 +/- 3.9) and 12/13 metastases were positive. Six patients with thin and 19 with thick melanoma with metallothionein expression died during a mean observation period of 6.4 +/- 1.8 and 3.6 +/- 2.5 years, respectively, their survival distribution function analyses giving statistically significant results for both the vertical tumour thickness (P < 0.0001) and metallothionein expression (P < 0.0001). These immunohistochemical results, based on routinely processed paraffin-embedded tissue, suggest that metallothionein expression in malignant melanoma is significantly associated with progressive disease and might therefore be a useful prognostic indicator.
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PMID:Immunohistochemically demonstrated metallothionein expression in malignant melanoma. 822 44

Eleven pairs of surgically resected lung cancers and corresponding non-neoplastic lung tissue were evaluated for metallothionein (MT) and metal content (cadmium and copper) by the heme/109Cd binding assay and atomic absorption spectroscopy, respectively. Tissue samples, obtained from patients ranging in age from 51 to 79, included six adenocarcinomas, two small cell carcinomas, one mixed cell carcinoma, one squamous cell carcinoma, and one carcinoma of non-primary origin (i.e., melanoma). Paired t-tests showed that metallothionein and copper concentrations in lung tumor tissue were significantly elevated when compared to non-malignant lung tissue. Cu was the major metal associated with the 10 kDa MT fraction in lung tumors whereas Cd was the primary metal bound to MT from non-neoplastic lung tissue. Since Cu-thionein is also known to be elevated in fetal lung tissue, the possibility exists that MT might represent an oncodevelopmental product which is useful as a biomarker for the early detection of lung carcinoma.
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PMID:Metallothionein in human lung carcinoma. 829 22

1-Carboranyl-3-(2-methylaziridino)-2-propanol (MACB) was prepared from the reaction of 1-carboranyl-2,3-epoxypropane with metalated methylaziridines having copper [Cu(CN)Li2]1/2 or lead (PbBu3) as the metal. MACB exhibited relatively high growth inhibition toward some cancer cells, and selective uptake of MACB by B-16 melanoma was accomplished.
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PMID:1-Carboranyl-3-(2-methylaziridino)-2-propanol. Synthesis, selective uptake by B-16 melanoma, and selective cytotoxicity toward cancer cells. 834 Sep 24

We analyzed and tried to characterize substance(s) responsible for cytotoxic activities detected in culture media conditioned by non pigmented B16 melanoma cells (NPB16). The different cytological tests used showed that ultrafiltrated conditioned media (CM U1 fraction) contained several cytotoxic factors with a Mw lower than 1000 Da. These factors seemed to act either directly or indirectly on cell membranes, mitochondria, on the cell cycle and on protein and DNA synthesis. A cytotoxic activity could be found even after high dilution of CM U1. These cytotoxic factors were rapidly released by B16 cells in culture, independently of cell confluence. Their activities in the treated cells were also very fast and the cytotoxic effects were irreversible after only a few hours of treatment. These factors were not intermediate products during melanogenesis, neither polyamines, nor proteases. At least one of them seemed to be a small acidic and basic stable peptide without disulfide bounds but not heat stable. The synthesis of at least one of these cytotoxic factors was inhibited by cycloheximide and the cytotoxic activity was partially destroyed by pronase and trypsin, but not by pepsin. The cytotoxicity was not modified by copper complexants or free radical inhibitors (bovine serum albumin (BSA), tyrosine, superoxyde dismutase (SOD), catalase, vitamin E). Furthermore the levels of glutathione peroxydase activity and reduced glutathione did not change after treatment by CM U1 as compared to controls.
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PMID:Characterization of non pigmented B16 melanoma cell-derived cytotoxic factors. 905 Nov 24

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

We studied the levels of serum copper and zinc as possible diagnostic factors or markers for the early detection of patients with melanoma. Levels were determined in 35 melanoma patients at various clinical stages and in 39 healthy persons. Measurements were performed by atomic absorption spectroscopy using 5100-PC-Perkin-Elmer equipment. We found that serum copper levels were very similar in the melanoma patients and the healthy individuals, the medium values being 118.32 +/- 25.32 micrograms/dl and 117.94 +/- 28.01 micrograms/dl, respectively. Therefore, no significant differences were observed with regard to copper levels. On the other hand, we obtained a medium value of 82.32 +/- 25.38 micrograms/dl for serum zinc levels in the melanoma patients and 56.72 +/- 11.79 micrograms/dl in the healthy persons, which represents a very significant increase in the serum levels of zinc in melanoma patients (P < 0.0001). A receiver operating characteristic (ROC) curve statistical analysis was also performed; the cut-off value obtained was 60.9 micrograms/dl. According to our results, zinc is increased in 86.5% of melanoma patients. Although further investigations are needed to assess its value in prognosis and follow-up, evaluation of serum zinc level could be a good tool to check for the presence of melanoma.
Melanoma Res 1998 Jun
PMID:Serum zinc levels are increased in melanoma patients. 966 50

The cytotoxic effects of beta-thujaplicin and five kinds of metal chelates were examined on mouse melanoma B16BL6 cells by cell viability and lactate dehydrogenase (LDH) release assay. Beta-thujaplicin-zinc chelate and beta-thujaplicin-copper chelate had higher cytotoxic effects than beta-thujaplicin, and the 50% effective doses (ED50) of these metal chelates were 12.5 and 25 microM, respectively. In addition, the zinc chelate induced DNA ladder formation in B16BL6 cells, as shown by the DNA fragmentation assay, suggesting that cell death induced by the zinc chelate is apoptosis. The zinc chelate also had a cytotoxic effect and induced DNA fragmentation on other tumor cell lines: HeLa, Meth A, and B16F1 cells, but not on normal human diploid fibroblasts FS-4. These results suggest that beta-thujaplicin-zinc chelate induces apoptotic cell death in various tumor cell lines and is a potent antitumor agent for tumor cells including malignant melanomas.
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PMID:Beta-thujaplicin zinc chelate induces apoptosis in mouse high metastatic melanoma B16BL6 cells. 988 34

It has been known for several decades that cutaneous depigmentation, i.e., contact/occupational vitiligo, can be caused by some phenolic derivatives that have a similar structure to tyrosine. Among these phenolic depigmenting agents, 4-tertiary butylphenol is the most potent. The cutaneous depigmentation induced by phenolic derivatives results from the loss of functional melanocytes. Tyrosinase is a melanocyte specific copper-containing enzyme that catalyzes the conversion of the amino acid tyrosine, through a complex series of intermediates, to melanin. In this study we tested the hypothesis that the cytotoxicity induced by 4-tertiary butylphenol is mediated by tyrosinase and occurs via an apoptotic process. Melanocyte cultures derived from African-American and Caucasian donors exhibiting a 3-fold difference in tyrosinase activity and 14-fold difference in melanin content demonstrate comparable concentration-dependent sensitivity to 4-tertiary butylphenol. In addition, cultures of dermal fibroblasts and epidermal keratinocytes exhibited similar and reduced sensitivity, respectively, to 4-tertiary butylphenol compared with autologous melanocytes. Two melanoma cell lines, one melanotic and one amelanotic lacking the expression of both tyrosinase protein and activity, when transfected with the tyrosinase cDNA, exhibited no alteration in its sensitivity to 4-tertiary butylphenol. These data suggest that 4-tertiary butylphenol cytotoxicity is not mediated via tyrosinase. Melanocytes treated with 4-tertiary butylphenol, however, did exhibit plasma membrane blebbing, DNA fragmentation, and phosphatidylserine relocalization indicating that 4-tertiary butylphenol induced melanocyte destruction occurs by an apoptotic process.
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PMID:The cytotoxicity and apoptosis induced by 4-tertiary butylphenol in human melanocytes are independent of tyrosinase activity. 1062 Jan 32

We investigated survival of two kinds of human embryonic cells (CLV102, Lu106) and human melanoma cells (Mel8) exposed to exogenous iron and copper ions in the absence or in the presence of ascorbic acid, catalase and superoxide dismutase. Iron ions produced cytotoxicity towards both kinds of cells dependent on its concentration. Catalase suppressed the cytotoxicity induced by iron ions in Lu106 cells. whereas in CLV102 and Mel8 cells, was ineffective. By contrast, superoxide dismutase abolished the cytotoxicity of iron ions towards CLV102 cells, whereas in Lu106 and Mel8 cells, was ineffective. The mixture of iron ions with ascorbic acid was less cytotoxic than iron ions themselves or ascorbic acid itself, only in CLV102 and Lu106 cells. Ascorbic acid enhanced drastically cytotoxic effect of copper ions in all kinds of cells.
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PMID:Influence of ascorbic acid on cytotoxic activity of copper and iron ions in vitro. 1124 46

Copper(II) complexes of 6-(2-chlorobenzylamino)purine (HL1) and 6-(3-chlorobenzylamino)purine (HL2), respectively, were prepared. Depending on the pH of the medium and the molar ratio of reactants the following mononuclear (trigonal-bipyramidal) and dinuclear (octahedral, trigonal-bipyramidal or tetrahedral) complexes were isolated: [Cu2(mu-HL1)2(mu-Cl2)2(HL1)2Cl2] (1a,b), [Cu2(mu-Cl)2(mu-L1)2(H2O)2] (2a), [Cu2(mu-Cl)2(mu-L2)2(H2O)2] (2b), [Cu(H+L2)2Cl3]Cl.H2O (3a,b), [Cu2(mu-Cl)2(HL1)2Cl2] (4a), and [Cu2(mu-Cl)2(HL2)2Cl2] (4b). The compounds were characterized by elemental analyses, electronic, infrared and mass (FAB+, ES+) spectral data, magnetic susceptibility temperature dependence measurements and molar conductivity data. An X-ray single-crystal structural analysis of [Cu(H+L2)2Cl3]Cl.2H2O (3b) showed that the Cu2+ ion is penta-coordinated by three chloride ions and by two H+L2 ligands. Thus, the Cu2+ ion adopts a distorted trigonal bipyramidal coordination geometry with the protonated H+L2 ligands coordinated in trans apical positions, while the three chloride ions are situated in an equatorial plane. The cytotoxic activity of the complexes was determined by a calcein AM assay. Mouse melanoma cell line B16-FO, human malignant melanoma cell line G361, human osteogenic sarcoma cell line HOS and human breast adenocarcinoma cell line MCF7 were used. IC50 values, the drug concentrations lethal to 50% of the tumor cells, were estimated. One of the important mechanisms responsible for the cytotoxicity of cytokinin-derived compounds, the inhibition of cyclin-dependent kinases by the studied complexes, was also determined.
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PMID:Preparation, physicochemical properties and biological activity of copper(II) complexes with 6-(2-chlorobenzylamino)purine (HL1) or 6-(3-chlorobenzylamino)purine (HL2). The single-crystal X-ray structure of. 1133 Apr 78


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