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)

Our previous studies have shown that a peptide corresponding to the residue sequence 185-203 of the NC1 domain of the alpha3 chain of basement membrane collagen (type IV) inhibits the activation of polymorphonuclear leukocytes. Peptides from the same region of the alpha1, alpha2, alpha4, and alpha5(IV) chains did not exhibit this property. Because of the intimate relationship between metastasizing neoplastic cells and vascular as well as epithelial basement membranes, we measured the cell adhesion-promoting activity of peptides from the NC1 domain of type IV collagen and their effect on proliferation of human melanoma cells. We found that peptide alpha3(IV)185-203 (CNYYSNSYSFWLASLNPER) not only promotes adhesion of human melanoma cells but also inhibits their proliferation. Adhesion increased by 50-60% over control. Melanoma cell proliferation was inhibited by 40% when cells were grown in a medium containing 5 microg/ml peptide for 5 days. Studies showed that replacement of serine in position 189 or 191 by alanine resulted in significantly reduced adhesion. Similarly, serine replacement resulted in reduced ability to inhibit proliferation. Our data suggest that a region of the NC1 domain of the alpha3(IV) chain, contained within the sequence 185-203, not only specifically promotes adhesion but also inhibits proliferation of melanoma cells. These properties appear to be dependent on the presence of the triplet sequence -SNS- (residues 189-191), which is unique to the alpha3 chain and may represent an important functional epitope.
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PMID:A cell binding domain from the alpha3 chain of type IV collagen inhibits proliferation of melanoma cells. 925 46

Tissue factor (TF) is a transmembrane glycoprotein that complexes with factor VIIa to initiate blood coagulation. It was reported in an earlier study that expression of high levels of TF in a human melanoma cell line promotes metastasis, and that the cytoplasmic domain of TF is required for this metastatic effect. To analyze the functions of the cytoplasmic and extracellular domains of TF in metastasis, two TF mutants were constructed; in one mutant alanine was substituted for each of the three serine residues in the cytoplasmic domain, preventing phosphorylation; in the other mutant alanine was substituted for four key residues in the extracellular domain, preventing binding of factor VIIa and consequently eliminating the initiation of blood coagulation by the TF-VIIa complex. Melanoma lines expressing high levels of either mutant form of TF were weakly metastatic in SCID mice, indicating that phosphorylation of the cytoplasmic domain and formation of a complex with VIIa by the extracellular domain are required for the full metastatic effect of TF. It was also found that increasing TF expression in human melanoma cells does not increase expression of vascular endothelial growth factor or promote growth and vascularization of tumors derived from the melanoma cells, suggesting that TF acts by a mechanism other than angiogenesis to promote metastasis.
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PMID:Role of tissue factor in metastasis: functions of the cytoplasmic and extracellular domains of the molecule. 1045 59

The Fas/FasL signalling system plays an important role in chemotherapy-induced apoptosis in several different cell types. After interferon-gamma (IFN-gamma) treatment, we have previously reported a significant increase in Fas expression in oral malignant melanoma cell lines (MMN9, PMP, MAA, HMG) in vitro, and combination therapy using IFN-gamma and anti-Fas antibody (CH-11) has shown a synergistic anti-proliferative effect in MMN9 cells. There have been several in-vitro studies using CH-11, but there are few reports of its anti-tumour effect in vivo. In this study, we investigated experimental therapy using anti-Fas antibody against MMN9 in vivo in a mouse model, and histologically examined tumour tissue removed from BALB/c nude mice. Animals that received both IFN-gamma and CH-11 showed a 53.8% increase in anti-tumour effect (P=0.0018) 20 days after the first administration. In the histological study, the combined administration group tested positive in terminal deoxynucleotidyl transferase-mediated nick end labelling staining, and showed significantly increased levels of Fas expression on immunostaining compared with the vehicle group. These results show the efficacy of anticancer therapy using IFN-gamma and anti-Fas antibody via the modulation of Fas-mediated apoptosis. Moreover, inhibition of IFN-gamma/CH-11-induced apoptosis with a general caspase inhibitor (benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone) reduced cell death significantly in vitro. Bcl-2 cleavage did not occur under these conditions, suggesting a relationship between caspase activation and Bc1-2 cleavage in MMN9 cells.
Melanoma Res 2005 Oct
PMID:Experimental therapy using interferon-gamma and anti-Fas antibody against oral malignant melanoma cells. 1617 66

Stem cell factor (SCF) activates a variety of signals associated with stimulation of proliferation, differentiation, migration, and survival in melanocytes. However, the molecular mechanisms by which SCF and its receptor Kit activates these signaling pathways simultaneously and independently are still poorly defined. Here, we examined whether SCF induces ezrin/radixin/moesin (ERM) proteins phosphorylation as a downstream target of PI3K in melanocytes. ERM proteins are cross-linkers between the plasma membrane and the actin cytoskeleton and are activated by phosphorylation of a C-terminal threonine residue. Our results demonstrated that SCF-induced ERM proteins phosphorylation on threonine residue and Rac1 activation in cultured normal human melanocytes through the activation of PI3K. The functional role of phosphorylated-ERM proteins was examined using melanocytes infected with adenovirus carrying a dominant negative mutant (Ala-558, TA) or wild type of moesin. In the TA moesin-overexpressing melanocytes, SCF-induced cell proliferation and migration were inhibited. Thus, our results indicate that phosphorylation of ERM proteins plays an important role in the regulation of SCF-induced melanocyte proliferation and migration.
Pigment Cell Melanoma Res 2009 Feb
PMID:Stem cell factor induces ERM proteins phosphorylation through PI3K activation to mediate melanocyte proliferation and migration. 1898 38

beta-N-methylamino-l-alanine (BMAA), a neurotoxic amino acid produced by cyanobacteria, has been suggested to be involved in the etiology of a neurodegenerative disease complex which includes Parkinson-dementia complex (PDC). In PDC, neuromelanin-containing neurons in substantia nigra are degenerated. Many PDC patients also have an uncommon pigmentary retinopathy. The aim of this study was to investigate the distribution of (3)H-BMAA in mice and frogs, with emphasis on pigment-containing tissues. Using autoradiography, a distinct retention of (3)H-BMAA was observed in melanin-containing tissues such as the eye and neuromelanin-containing neurons in frog brain. Analysis of the binding of (3)H-BMAA to Sepia melanin in vitro demonstrated two apparent binding sites. In vitro-studies with synthetic melanin revealed a stronger interaction of (3)H-BMAA with melanin during synthesis than the binding to preformed melanin. Long-term exposure to BMAA may lead to bioaccumulation in melanin- and neuromelanin-containing cells causing high intracellular levels, and potentially changed melanin characteristics via incorporation of BMAA into the melanin polymer. Interaction of BMAA with melanin may be a possible link between PDC and pigmentary retinopathy.
Pigment Cell Melanoma Res 2009 Feb
PMID:Retention of the cyanobacterial neurotoxin beta-N-methylamino-l-alanine in melanin and neuromelanin-containing cells--a possible link between Parkinson-dementia complex and pigmentary retinopathy. 1915 35

The tyrosine kinase receptor KIT and the transcription factor MITF, each required for melanocyte development, have been shown to interact functionally both in vitro and in vivo. In vitro, KIT signaling leads to MITF phosphorylation, affecting MITF activity and stability. In vivo, the presence of the Mitf (Mi-wh) allele exacerbates the spotting phenotype associated with heterozygosity for Kit mutations. Here, we show that among a series of other Mitf alleles, only the recessive Mitf (mi-bws) mimics the effect of Mitf (Mi-wh) on Kit. Intriguingly, Mitf (mi-bws) is characterized by a splice defect that leads to a reduction of RNAs containing MITF exon 2B which encodes serine-73, a serine phosphorylated upon KIT signaling. Nevertheless, other Mitf alleles that generally affect Mitf RNA levels, or carry a serine-73-to-alanine mutation that specifically reduces exon 2B-containing RNAs, do not show similar interactions with Kit in vivo. We conclude that the recessive Mitf (mi-bws) is a complex allele that can display a semi-dominant effect when present in a Kit-sensitized background. We suggest that human disease variability may equally be due to complex, allele-specific interactions between different genes.
Pigment Cell Melanoma Res 2010 Jun
PMID:Allele-specific genetic interactions between Mitf and Kit affect melanocyte development. 2037 22

In this perspective, we revise the historic notion that cancer is a disease of mitochondria. We summarize recent findings on the function and rewiring of central carbon metabolism in melanoma. Metabolic profiling studies using stable isotope tracers show that glycolysis is decoupled from the tricarboxylic acid (TCA) cycle. This decoupling is not 'dysfunction' but rather an alternate wiring required by tumor cells to remain metabolically versatile. In large part, this requirement is met by glutamine feeding the TCA cycle as an alternative source of carbon. Glutamine is also used in non-conventional ways, like traveling in reverse through the TCA flux to feed fatty acid biosynthesis. Biosynthetic networks linked with non-essential amino acids alanine, serine, arginine, and proline are also significantly impacted by the use of glutamine as an alternate carbon source.
Pigment Cell Melanoma Res 2012 Nov
PMID:Glutamine-fueled mitochondrial metabolism is decoupled from glycolysis in melanoma. 2284 58

Melanoma is a type of cancer that reaches more people in the world, characterized by genetic mutations that trigger the growth of disorganized cells. The diagnosis of skin tumors by invasive techniques has become a risk to the patients, so the search for new non-invasive techniques has been the subject of research in recent years. The objective of this work is to propose a non-invasive method prognosis based on the identification of specific biomarkers of the cancer, known as metabolomics analysis. For this study, we used B16F10 melanoma tumor cells and metabolic profiles were obtained at three time-periods by (1)HNMR and comparison with the cell cycle, apoptosis pathways and proliferation index. The metabolic profiles show the relationship between the metabolites found with energy metabolism, pathways of apoptosis and proliferation, which showed increases in proportion during growth and progression. Were found 29 metabolites, of which the differentially expressed are: lactate, aspartate, glycerol, lipids, alanine, myo-inositol, phosphocholine, choline, acetate, creatine and taurine. Choline and creatine are closely related with tumor progression, and are inversely expressed in later stages of tumor growth, which demonstrates the ability to be markers of tumor progression or monitoring the pharmacological efficacy when combined with other therapies. We conclude that the metabolome appeared as effective non-invasive technique predicts, besides providing possible biomarkers of melanoma.
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PMID:Prognostic relationship of metabolic profile obtained of melanoma B16F10. 2343 55

Melanoma is the fatal form of skin cancer. Herein, a three-dimensional quantitative structure-activity relationship study on a series of 105 colchicine binding site-targeted 2-arylthiazolidine-4-carboxylic acid amides (ATCAA) derivatives as melanoma antagonists was conducted. The optimal CoMSIA model yields a Q(2) of 0.556, R(2)(ncv) of 0.833 and R(2)(pred) of 0.757, while the CoMFA yields a Q(2) of 0.569, R(2)(ncv) of 0.812 and R(2)(pred) of 0.589. In addition, molecular docking was also carried out. The study results demonstrated that: (1) Bulky substituents in Rings C and D significantly increase the biological activity of compounds while decrease the activity at Rings A and B; (2) Electropositive groups at Rings A and B as well as electronegative groups at Ring C help to increase the activity; (3) HB donor favors Rings A and D while HB acceptor favors Rings B and C. Besides, a statistical analysis of the key amino acids as well as the ones forming HB with various antagonists of the colchicine binding site was conducted based on 34 essays and found HB to be the key interaction that MTAs have with the colchicine binding site and that Ala 250, Asn 258, Thr 179, Lys 254 and Lys 352 are vital in the composition of the site and the formation of HB. The results of this study provide useful information on designing antagonists with improved activity and insight on the composition of the colchicine binding site.
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PMID:Structural analysis for colchicine binding site-targeted ATCAA derivatives as melanoma antagonists. 2362 86

Melanoma is a malignant tumor of melanocytes. Although extensive investigations have been done to study metabolic changes in primary melanoma in vivo and in vitro, little effort has been devoted to metabolic profiling of metastatic tumors in organs other than lymph nodes. In this work, NMR-based metabolomics combined with multivariate data analysis is used to study metastatic B16-F10 melanoma in C57BL/6J mouse spleen. Principal Component Analysis (PCA), an unsupervised multivariate data analysis method, is used to detect possible outliers, while Orthogonal Projection to Latent Structure (OPLS), a supervised multivariate data analysis method, is employed to find important metabolites responsible for discriminating the control and the melanoma groups. Two different strategies, i.e. spectral binning and spectral deconvolution, are used to reduce the original spectral data before statistical analysis. Spectral deconvolution is found to be superior for identifying a set of discriminatory metabolites between the control and the melanoma groups, especially when the sample size is small. OPLS results show that the melanoma group can be well separated from its control group. It is found that taurine, glutamate, aspartate, O-Phosphoethanolamine, niacinamide,ATP, lipids and glycerol derivatives are decreased statistically and significantly while alanine, malate, xanthine, histamine, dCTP, GTP, thymidine, 2'-Deoxyguanosine are statistically and significantly elevated. These significantly changed metabolites are associated with multiple biological pathways and may be potential biomarkers for metastatic melanoma in spleen.
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PMID:1H NMR Metabolomics Study of Metastatic Melanoma in C57BL/6J Mouse Spleen. 2538 71


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