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

Melanins are ubiquitous catecholic pigments, formed in organelles called melanosomes within melanocytes, the function of which is to protect skin against harmful effects of UV radiation. Melanosomes within melanoma cells are characteristically abnormal, with fragmented melanin and disrupted membranes. We hypothesize that the disruption of melanosomal melanin might be an early event in the etiology and progression of melanoma, leading to increased oxidative stress and mutation. In this report, we examine the effect of a combination of UV treatment and metal ion exposure on melanosomes within melanocytes, as well as their ability to act as pro-oxidants in ex situ experiments, and assay the effects of this treatment on viability and cell cycle progression. UVB exposure causes morphologic changes of the cells and bleaching of melanosomes in normal melanocytes, both significantly enhanced in Cu(II) and Cd(II)-treated cells, as observed by microscopy. The promoted bleaching by Cu(II) is due to its ability to redox cycle under oxidative conditions, generating reactive oxygen species; verified by the observed enhancement of hydroxyl radical generation when isolated melanosomes were treated with both Cu(II) ions and UVB, as assayed by DNA clipping. Single-dose UVB/Cu treatment does not greatly affect cell viability or cell cycle progression in heavily pigmented cells, but did so in an amelanotic early stage melanoma cell line.
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PMID:Melanosomal damage in normal human melanocytes induced by UVB and metal uptake--a basis for the pro-oxidant state of melanoma. 1833 99

Melanoma is a highly invasive tumor with elevated mortality rates. Progression and aggressiveness appear related to the achievement of an angiogenic phenotype. Melanoma cells express several angiogenic factors, including fibroblast growth factor (FGF)-1 and FGF-2. The autocrine production and release of FGFs and the subsequent activation of FGF receptors, have a central role in melanoma tumor progression. We demonstrated that FGF-1 is secreted from a human melanoma cell line, A375, under conditions of serum deprivation. The release of FGF-1 is inhibited by the copper chelator ammonium tetrathiomolybdate, suggesting a role of copper in the secretory pathway, and is triggered by activation of phosphatidylinositol 3-kinase (PI3K)/Akt intracellular signaling. Interestingly, overexpression or activation of Akt has been correlated with poor prognosis in melanoma patients. Our data indicate a novel role for Akt in supporting the progression of human melanomas and advocate the need for new treatments targeting PI3K/Akt signaling pathway, to control tumor development and progression.
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PMID:The release of fibroblast growth factor-1 from melanoma cells requires copper ions and is mediated by phosphatidylinositol 3-kinase/Akt intracellular signaling pathway. 1840 Mar 76

The in vitro cytotoxicities of a number of gold(I), silver(I) and copper(I) complexes containing chiral tertiary phosphine ligands have been examined against the mouse tumour cell lines P815 mastocytoma, B16 melanoma [gold(I) and silver(I) compounds] and P388 leukaemia [gold(I) complexes only] with many of the complexes having IC(50) values comparable to that of the reference compounds cis-diamminedichloroplatinum(ll), cisplatin, and bis[1,2-bis(diphenylphosphino) ethane]gold(I) iodide. The chiral tertiary phosphine ligands used in this study include (R)-(2-aminophenyl)methylphenylphosphine; (R,R)-, (S,S)- and (R(*),R(*))-1,2-phenylenebis(methylphenylphosphine); and (R,R)-, (S,S)- and (R(*),R(*))-bis{(2-diphenylphosphinoethyl)phenylphosphino}ethane. The in vitro cytotoxicities of gold(I) and silver(I) complexes containing the optically active forms of the tetra(tertiary phosphine) have also been examined against the human ovarian carcinoma cell lines 41M and CH1, and the cisplatin resistant 41McisR, CH1cisR and SKOV-3 tumour models. IC(50) values in the range 0.01 - 0.04 muM were determined for the most active compounds, silver(I) complexes of the tetra(tertiary phosphine). Furthermore, the chirality of the ligand appeared to have little effect on the overall activity of the complexes: similar IC(50) data were obtained for complexes of a particular metal ion with each of the stereoisomeric forms of a specific ligand.
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PMID:Antitumor activity of gold(i), silver(i) and copper(i) complexes containing chiral tertiary phosphines. 1847 46

The efficacy of ellagic acid (EA), one of the naturally occurring polyphenols, in inhibiting melanogenesis was examined in vitro and in vivo. When mushroom-derived tyrosinase, a metaloprotein containing copper, was incubated with EA, enzymatic activity tended to decrease with decreasing copper concentration. Enzyme activity partially recovered when copper was added to the inactivated enzyme. Tyrosinase activity in the B16 melanoma cells was observed to recover in a dose-dependent manner when copper ions were added to the medium containing EA. Based on these results, EA is thought to react specifically with the copper located at the active centre of the tyrosinase molecule. Furthermore, when EA was applied for 6 weeks to brownish guinea-pigs, which have melanocytes in their skin, at the same time as irradiating for 2 weeks with ultra-violet light, skin pigmentation was clearly suppressed and the skin to which EA had been applied showed features similar to that of non-irradiated skin. These areas were irradiated again when the application of EA had been completed, and skin pigmentation occurred at the former site of EA application. In similar studies with hydroquinone, re-pigmentation did not occur on the sites at which hydroquinone (1%) had been applied. Based on the results reported here, EA is thought to suppress melanogenesis by reacting with activated melanocytes and without injuring cells.
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PMID:In vitro and in vivo evaluation of ellagic acid on melanogenesis inhibition. 1850 16

A study of magnetic susceptibility and electron spin resonance (E.S.R.) spectra of Cloudman S91 and S91A melanomas and various mouse tissues was correlated with trace-metal analysis and known biochemical reactions. Average magnetic moments obtained from temperature-dependence studies showed the following order for tissues: S91>S91A>leg muscle. These results indicated a similar order in the relative concentration of magnetic species (free radicals and/or paramagnetic ions) and were confirmed by E.S.R. The E.S.R. spectra at different power levels showed that the free radical activity and the Cu2+ and Fe3+ activity attributed to different signals was generally higher in S91 than in S91A, which did not show an Fe3+ type signal. Normal tissues such as liver, spleen, heart, kidney, brain, and leg muscle showed varying amounts of free radical activity but not signals attributable to paramagnetic ions. E.S.R. spectra and trace-metal analysis at different stages of S91 tumor growth indicated a systematic increase in the free rad cal activity, total copper and iron concentrations, and paramagnetic ions, presumed to be Cu2+ and Fe3+. The S91A melanoma showed increase in total copper, but not in free radical and paramagnetic ion (CU2+) activity after the initial growth. Correlation of these findings with known biochemical reactions suggests that the free radical activity may be attributed partly to melanin and intermediates of various enzymatic reactions. Presumed paramagnetic ion activity cannot yet be ascribed to specific biostates.
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PMID:Magnetic susceptibility and electron spin resonance absorption spectra of mouse melanomas S91 and 591A. 1862 33

A 53-year-old woman with a history of melanoma status-post excision two years prior presented with a 4-month history of 4, dark-brown macules on the inferior surface of her tongue. A biopsy specimen showed a squamous mucosa with chronic submucosal inflammation and brown pigment. The clinical and histopathologic findings were consistent with a diagnosis of amalgam tattoo. Amalgam tattoos are common, oral pigmented lesions that clinically present as isolated, blue, grey, or black macules on the gingivae, the buccal and alveolar mucosae, the palate, and/or the tongue. They are due to deposition of a mixture of silver, tin, mercury, copper, and zinc, which are components of an amalgam filling, into the oral soft tissues. Amalgam tattoos can either be treated surgically or with a Q-switched ruby laser. In the case of our patient with the history of melanoma, her oral lesions proved not to be the more dire diagnosis of malignant melanoma.
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PMID:Amalgam tattoo. 1862 55

Tyrosinase is a mono-oxygenase with a dinuclear copper catalytic center which is able to catalyze both the ortho-hydroxylation of monophenols (cresolase activity) and the oxidation of catechols (catecholase activity) yielding ortho-quinone products. Tyrosinases appear to have arisen early in evolution and are widespread in living organisms where they are involved in several processes, including antibiosis, adhesion of molluscs, the hardening of the exoskeleton of insects, and pigmentation. Tyrosinase is the principal enzyme of melanin formation in vertebrates and is of clinical interest because of the possible utilization of its activity for targeted treatment of malignant melanoma. Tyrosinase is characterised by an irreversible inactivation that occurs during the oxidation of catechols. In a recent publication we proposed a mechanism to account for this feature based on the ortho-hydroxylation of catecholic substrates, during which process Cu(II) is reduced to Cu(0) which no longer binds to the enzyme and is eliminated (reductive elimination). Since this process is dependent on cresolase activity of tyrosinase, a strong prediction of the proposed inactivation mechanism is that it will not be exhibited by enzymes lacking cresolase activity. We show that the catechol oxidase readily extracted from bananas (Musa cavendishii) is devoid of cresolase activity and that the kinetics of catechol oxidation do not exhibit inactivation. We also show that a species with the molecular mass of the putative cresolase oxidation product is formed during tyrosinase oxidation of 4-methylcatechol. The results presented are entirely consistent with our proposed mechanism to account for suicide-inactivation of tyrosinase.
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PMID:Evidence consistent with the requirement of cresolase activity for suicide inactivation of tyrosinase. 1898 57

High mortality rate for metastatic melanoma is related to its resistant to the current methods of therapy. Melanogenesis is a metabolic pathway characteristic for normal and malignant melanocytes that can affect the behavior of melanoma cells or its surrounding environment. Human melanoma cells in which production of melanin pigment is dependent on tyrosine levels in medium were used for experiments. Peripheral blood mononuclear cells were derived from the buffy coats purchased from Lifeblood Biological Services. Cell pigmentation was evaluated macroscopically, and tyrosinase activity was measured spectrophotometrically. Cell proliferation and viability were measured using lactate dehydrogenase release MTT, [(3)H]-thymidine incorporation and DNA content analyses, and gene expression was measured by real time RT-PCR. Pigmented melanoma cells were significantly less sensitive to cyclophosphamide and to killing action of IL-2-activated peripheral blood lymphocytes. The inhibition of melanogenesis by either blocking tyrosinase catalytic site or chelating copper ions sensitized melanoma cells towards cytotoxic action of cyclophosphamide, and amplified immunotoxic activities of IL-2 activated lymphocytes. Exogenous L-DOPA inhibited lymphocyte proliferation producing the cell cycle arrest in G1/0 and dramatically inhibited the production of IL-1beta, TNF-alpha, IL-6 and IL-10. Thus, the active melanogenesis could not only impair the cytotoxic action of cyclophosphamid but also has potent immunosuppressive properties. This resistance to a chemotherapeutic agent or immunotoxic activity of lymphocytes could be reverted by the action of tyrosinase inhibitors. Thus, the inhibition of melanogenesis might represent a valid therapeutic target for the management of advanced melanotic melanomas.
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PMID:Inhibitors of melanogenesis increase toxicity of cyclophosphamide and lymphocytes against melanoma cells. 1908 34

The members of the S100 protein family are multifunctional proteins with a regulatory role in a variety of cellular processes. They exert their actions usually through calcium binding, although Zn2+ and Cu2+ have also been shown to regulate their biological activity. The most studied member, protein S100B, exhibits neurotrophic (at physiologic concentration) or neurotoxic (at higher concentration) activity and its immunohistochemical expression or serum levels have been determined in various clinical disorders. S100B has been well documented as a marker of astrocytic activation mediating its effects via interaction with receptor for advanced glycation end products (RAGE). We herein provide a wide range of information concerning their clinical application in traumatic brain injuries, Alzheimer disease, subarachnoid haemorrhage and other neurologic disorders, malignant melanoma and several other neoplasms (as S100B has been shown to down-regulate p53), as well as inflammatory diseases. Also its use on predicting neurologic outcome after resuscitation for cardiac arrest or in intrauterine growth retardation newborns is discussed.
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PMID:S100 protein family and its application in clinical practice. 1915 63

Phenoloxidases (POs) occur in all organisms and are involved in skin and hair coloring in mammals, and initiating melanization in wound healing. Mutation or overexpression of PO can cause albinism or melanoma, respectively. SDS can convert inactive PO and the oxygen carrier hemocyanin (Hc) into enzymatically active PO. Here we present single-particle cryo-EM maps at subnanometer resolution and pseudoatomic models of the 24-oligomeric Hc from scorpion Pandinus imperator in resting and SDS-activated states. Our structural analyses led to a plausible mechanism of Hc enzyme PO activation: upon SDS activation, the intrinsically flexible Hc domain I twists away from domains II and III in each subunit, exposing the entrance to the active site; this movement is stabilized by enhanced interhexamer and interdodecamer interactions, particularly in the central linker subunits. This mechanism could be applicable to other type 3 copper proteins, as the active site is highly conserved.
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PMID:Structural mechanism of SDS-induced enzyme activity of scorpion hemocyanin revealed by electron cryomicroscopy. 1944 30


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