Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1522102 (Melanoma)
 7,698 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of iron chelates to promote hydroxyl radical (.OH) formation from hydrogen peroxide (H2O2) via Fenton chemistry was exploited to detect H2O2 produced during the oxidations of the eumelanin precursors 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA). H2O2 generation during the autooxidations of DHI and DHICA was confirmed on the basis of the electrochemical detection of three hydroxylation products of salicylate [2,3 and 2,5-dihydroxybenzoic acid (DHBA) and catechol], which was used as an .OH indicator. The oxidations of both 5,6-dihydroxyindoles were augmented by tyrosinase and peroxidase without the addition of H2O2. The partial inhibitions by catalase of the auto-oxidations and tyrosinase- and peroxidase-mediated oxidations of DHI and DHICA provide additional evidence of an endogenous origin of H2O2 during the final stages of eumelanogenesis. The mechanism proposed for the formation of H2O2 involves the semiquinones of DHI and DHICA in the univalent transfer of electrons to molecular oxygen. The observations described in this study support previous reports suggesting that factors modulating the levels of H2O2 in melanocytes and melanoma cells play critical roles in directing the course of melanogenesis and influencing the potential cytotoxicity of the biosynthetic pathways.
Melanoma Res 1996 Oct
PMID:Hydrogen peroxide generation associated with the oxidations of the eumelanin precursors 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid. 890 94

Previous studies have shown that sensitivity to high extracellular levels of Zn2+ is a general feature of cells in vitro and that a prerequisite of the toxic action of zinc is entry into cells via channels that are shared with iron or calcium. As the biochemical and toxicological behaviour of zinc chelate complexes could be different from that of free Zn2+, the effect of chelating agents on zinc transport into human melanoma cell lines was tested. EDTAcal and tetracycline reduced the toxic action of zinc ions in vitro, whereas phenytoin and diethyldithiocarbamate potentiated its effects. D-penicillamine, an effective chelator of zinc in vivo, also exerted a protective action in vitro. Comparison of sensitivity to Zn2+ in vitro between human melanoma lines and several lines of pigment cells from skin of various origins demonstrated that melanoma cells are killed by zinc ions at concentrations which are only partially toxic for normal pigment cells. This is consistent with the repeatedly observed high uptake of 65Zn by melanoma cells.
Melanoma Res 1997 Dec
PMID:Cytotoxic interactions of Zn2+ in vitro: melanoma cells are more susceptible than melanocytes. 946 16

CDKN2A is regarded as a major melanoma susceptibility gene. A 19 bp deletion has been detected within Dutch families with familial atypical multiple mole-melanoma syndrome. Genetic analysis revealed two individuals with germline deletions in both copies of CDKN2A. One of them did not develop atypical naevi or melanoma, but died of adenocarcinoma at the age of 54 years. This report describes the results of the investigation of the second p16-null individual, who was also found to have glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and who has developed many atypical naevi and seven melanomas. Using electron microscopic techniques, striking alterations in melanosomal structures and deviations in their sulphur, iron and calcium composition indicating a strong preference for phaeomelanogenesis and increased oxidative stress were found in the naevus cells of the patient. Using an in vitro model, we demonstrated that leaking melanin precursors may strongly enhance oxidative DNA damage through iron release from ferritin. We conclude that the homozygous p16 deletion is not sufficient for the development of a dysplastic naevus phenotype and melanoma. However, when an additional modifying factor, such as G-6-PD deficiency, increases the level of oxidative DNA damage in melanin-producing cells, the risk of developing atypical naevi and their malignant transformation may increase significantly.
Melanoma Res 2003 Apr
PMID:Homozygous germline mutation of CDKN2A/p16 and glucose-6-phosphate dehydrogenase deficiency in a multiple melanoma case. 1269 Mar 1

Sodium ascorbate (vitamin C) has a reputation for inconsistent effects upon malignant tumor cells, which vary from growth stimulation to apoptosis induction. Melanoma cells were found to be more susceptible to vitamin C toxicity than any other tumor cells. The present study has shown that sodium ascorbate decreases cellular iron uptake by melanoma cells in a dose- and time-dependent fashion, indicating that intracellular iron levels may be a critical factor in sodium ascorbate-induced apoptosis. Indeed, sodium ascorbate-induced apoptosis is enhanced by the iron chelator, desferrioxamine (DFO) while it is inhibited by the iron donor, ferric ammonium citrate (FAC). Moreover, the inhibitory effects of sodium ascorbate on intracellular iron levels are blocked by addition of transferrin, suggesting that transferrin receptor (TfR) dependent pathway of iron uptake may be regulated by sodium ascorbate. Cells exposed to sodium ascorbate demonstrated down-regulation of TfR expression and this precedes sodium ascorbate-induced apoptosis. Taken together, sodium ascorbate-mediated apoptosis appears to be initiated by a reduction of TfR expression, resulting in a down-regulation of iron uptake followed by an induction of apoptosis. This study demonstrates the specific mechanism of sodium ascorbate-induced apoptosis and these findings support future clinical trial of sodium ascorbate in the prevention of human melanoma relapse.
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PMID:Sodium ascorbate (vitamin C) induces apoptosis in melanoma cells via the down-regulation of transferrin receptor dependent iron uptake. 1567 19

Melanoma incidence has been steadily increasing in recent years in most western countries, thus suggesting a role of environmental risk factors. Among these determinants, it has been hypothesized that some trace elements of nutritional and toxicological interest may be implicated in the etiology of the disease. We examined patients with newly diagnosed melanoma of the skin and population controls from the Modena province northern Italy. Clinical and dietary data were collected through questionnaires, and toenails were sampled for trace element determination. Levels of cadmium, chromium, lead, selenium, zinc, copper and iron in toenails were measured by inductively coupled plasma optical emission spectrometry and by neutron activation analysis. Data obtained from 58 cases and 58 controls indicated higher levels of copper and lower concentrations of iron in melanoma patients, whilst no other differences were seen for the remaining elements. Patterns of correlations of zinc and copper with the estimated intake of some dietary factors were different between cases and controls. Results of the present study suggest that abnormal intake or metabolism of copper and of iron might be implicated in the etiology of melanoma, whilst they do not indicate an involvement of exposure to cadmium, chromium, lead, selenium and zinc in this disease.
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PMID:Trace elements and melanoma. 1624 Jun 75

Melanoma tumor antigen p97 or melanotransferrin (MTf) is an iron (Fe)-binding protein with high homology to serum transferrin. MTf is expressed at very low levels in normal tissues and in high amounts in melanoma cells although its function remains elusive. To understand the function of MTf, we utilized whole-genome microarray analysis to examine the gene expression profile of five models after modulating MTf expression. These models included two new stably transfected MTf hyper-expression models (SK-N-MC neuroepithelioma and LMTK- fibroblasts) and one cell type (SK-Mel-28 melanoma) where MTf was down-regulated by post-transcriptional gene silencing. These findings were compared with alterations in gene expression identified using the MTf-/- mice. In addition, the changes identified from the microarray data were also assessed in a new model of MTf down-regulation in SK-Mel-2 melanoma cells. In the cell line models, MTf hyper-expression led to increased proliferation, whereas MTf down-regulation resulted in decreased proliferation. Across all five models of MTf down- and up-regulation, we identified three genes modulated by MTf. These included ATP-binding cassette subfamily B member 5, whose change in expression mirrored MTf down- or up-regulation. In addition, thiamine triphosphatase and transcription factor 4 were inversely expressed relative to MTf levels across all five models. The products of these three genes are involved in membrane transport, thiamine phosphorylation and proliferation/survival, respectively. This study identifies novel molecular targets directly or indirectly regulated by MTf and the potential pathways involved in its function, including modulation of proliferation.
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PMID:Identification of distinct changes in gene expression after modulation of melanoma tumor antigen p97 (melanotransferrin) in multiple models in vitro and in vivo. 1744 3

Metastasis is responsible for most deaths due to malignant melanoma. The clinical significance of micrometastases in the lymph is a hotly debated topic, but an improved understanding of the lymphatic spread of cancer remains important for improving cancer survival. Cellular magnetic resonance imaging (MRI) is a newly emerging field of imaging research that is expected to have a large impact on cancer research. In this study, we demonstrate the cellular MRI technology required to reliably image the lymphatic system in mice and to detect iron-labeled metastatic melanoma cells within the mouse lymph nodes. Melanoma cells were implanted directly into the inguinal lymph nodes in mice, and micro-MRI was performed using a customized 1.5-T clinical MRI system. We show cell detection of as few as 100 iron-labeled cells within the lymph node, with injections of larger cell numbers producing increasingly obvious regions of signal void. In addition, we show that cellular MRI allows monitoring of the fate of these cells over time as they develop into intranodal tumors. This technology will allow noninvasive investigations of cellular events in cancer metastasis within an entire animal and will facilitate progress in understanding the mechanisms of metastasis within the lymphatic system.
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PMID:Cellular magnetic resonance imaging: in vivo imaging of melanoma cells in lymph nodes of mice. 1832 65

A magnetite nanoparticle, NPrCAP/M, was produced for intracellular hyperthermia treatment of melanoma by conjugating N-propionyl-cysteaminylphenol (NPrCAP) with magnetite and used for the study of selective targeting and degradation of melanoma cells. NPrCAP/M, like NPrCAP, was integrated as a substrate in the oxidative reaction by mushroom tyrosinase. Melanoma, but not non-melanoma, cells incorporated larger amounts of iron than magnetite from NPrCAP/M. When mice bearing a B16F1 melanoma and a lymphoma on opposite flanks were given NPrCAP/M, iron was observed only in B16F1 melanoma cells and iron particles (NPrCAP/M) were identified within late-stage melanosomes by electron microscopy. When cells were treated with NPrCAP/M or magnetite and heated to 43 degrees C by an external alternating magnetic field (AMF), melanoma cells were degraded 1.7- to 5.4-fold more significantly by NPrCAP/M than by magnetite. Growth of transplanted B16 melanoma was suppressed effectively by NPrCAP/M-mediated hyperthermia, suggesting a clinical application of NPrCAP/M to lesional therapy for melanoma. Finally, melanoma cells treated with NPrCAP/M plus AMF showed little sub-G1 fraction and no caspase 3 activation, suggesting that the NPrCAP/M-mediated hyperthermia induced non-apoptotic cell death. These results suggest that NPrCAP/M may be useful in targeted therapy for melanoma by inducing non-apoptotic cell death after appropriate heating by the AMF.
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PMID:N-propionyl-cysteaminylphenol-magnetite conjugate (NPrCAP/M) is a nanoparticle for the targeted growth suppression of melanoma cells. 1929 15

Nanosecond pulsed electric fields (nsPEFs) can affect the intracellular structures of cells in vitro. This study shows the direct effects of nsPEFs on tumor growth, tumor volume, and histological characteristics of normal skin and B16-F10 melanoma in SKH-1 mice. A melanoma model was set up by injecting B16-F10 into female SKH-1 mice. After a 100-pulse treatment with an nsPEF (40-kV/cm field strength; 300-ns duration; 30-ns rise time; 2-Hz repetition rate), tumor growth and histology were studied using transillumination, light microscopy with hematoxylin and eosin stain and transmission electron microscopy. Melanin and iron within the melanoma tumor were also detected with specific stains. After nsPEF treatment, tumor development was inhibited with decreased volumes post-nsPEF treatment compared with control tumors (P<0.05). The nsPEF-treated tumor volume was reduced significantly compared with the control group (P<0.01). Hematoxylin and eosin stain and transmission electron microscopy showed morphological changes and nuclear shrinkage in the tumor. Fontana-Masson stain indicates that nsPEF can externalize the melanin. Iron stain suggested nsPEF caused slight hemorrhage in the treated tissue. Histology confirmed that repeated applications of nsPEF disrupted the vascular network. nsPEF treatment can significantly disrupt the vasculature, reduce subcutaneous murine melanoma development, and produce tumor cell contraction and nuclear shrinkage while concurrently, but not permanently, damaging peripheral healthy skin tissue in the treated area, which we attribute to the highly localized electric fields surrounding the needle electrodes.
Melanoma Res 2009 Dec
PMID:Histopathology of normal skin and melanomas after nanosecond pulsed electric field treatment. 1973 Apr 4

Melanogenesis substrate, N-propionyl-4-S-cysteaminylphenol (NPrCAP) is specifically taken up by melanoma cells and inhibits their growth by producing cytotxic free radicals. By taking advantage of this unique chemical agent, we have established melanoma-targeting intracellular hyperthermia by conjugating NPrCAP with magnetite nanoparticles (NPrCAP/M) upon exposure to an alternating magnetic field (AMF). This treatment causes cytotoxic reaction as well as heat shock responses, leading to elicitation of antitumor immune response, which was proved by tumor rechallenge test and CTL induction. We found the level of heat shock protein 72 (Hsp72) to be increased in the cell lysate and culture supernatant after intracellular hyperthermia. Melanoma-specific CD8(+) T-cell response to dendritic cells loaded with hyperthermia-treated tumor lysate was enhanced when compared with non-treated tumor lysate. When heat shock protein, particularly Hsp72, was immuno-depleted from hyperthermia-treated tumor cell lysate, specific CD8(+) T-cell response was abolished. Thus, it is suggested that antitumor immune response induced by hyperthermia using NPrCAP/M is derived from the release of HSP-peptide complex from degraded tumor cells. Therefore, this chemo-thermo-immuno (CTI)-therapy might be effective not only for primary melanoma but also for distant metastasis because of induction of systemic antimelanoma immune responses.
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PMID:Melanoma-targeted chemo-thermo-immuno (CTI)-therapy using N-propionyl-4-S-cysteaminylphenol-magnetite nanoparticles elicits CTL response via heat shock protein-peptide complex release. 2059 94


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