Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Researchers have suggested that the increased longitudinal relaxation rates (1/T1) of solvent water protons often found in melanoma result either from the paramagnetism of stable free radicals occurring in melanin or from that of methemoglobin in nonacute hemorrhagic regions of the tumor. However, field-cycling relaxometry and model solutions of synthetic melanin produced data which show that free radicals in melanin do not contribute significantly to 1/T1; instead, aggregation of melanin into macromolecular particles and binding of biologically-common paramagnetic metal ions (ie Fe3+, Mn2+, and Cu2+) to melanin effectively do increase 1/T1. These data have been combined with published histochemical data on melanin-containing tissues, while disregarding any additional effect related to hemorrhage. The result indicates that in melanoma the expected contribution of melanin-bound Fe3+ to 1/T1, at typical imaging fields, predominates under estimated in vivo conditions; furthermore, the total contribution from all sources, specifically due to the presence of melanin, is sufficient to account for reported measurements of 1/T1 in melanoma. Comparing the latter results with published data on T1 relaxation in model solutions of methemoglobin suggests that co-existing regions of nonacute microhemorrhage also may contribute significantly to 1/T1 under certain conditions. Finally, the implications for 1/T2 of melanin occurring in vivo within discrete melanosomes is discussed.
 ...
PMID:Sources of the increased longitudinal relaxation rates observed in melanotic melanoma. An in vitro study of synthetic melanins. 250 76

The effect of zinc ions on B16 mouse melanoma lines, HeLa cells and I-221 epithelial cells was investigated in vitro in order to ascertain whether sensitivity to Zn2+ is a general feature of cells in vitro and in an attempt to elucidate the mechanism(s) of zinc cytotoxicity. The proliferation of B16, HeLa and I-221 cell lines was inhibited by 1.25 x 10(-4), 1.50 x 10(-4) and 1.50 x 10(-4) mol/l Zn2+, respectively. The free radical scavengers, methimazole and ethanol, did not suppress the toxicity of Zn2+, neither did superoxide dismutase or catalase. The addition of the chelating agent EDTA reduced the zinc cytotoxicity. It was possible to suppress the cytotoxicity of zinc by increasing the concentration of either Fe2+ or Ca2+ but not Mg2+, which suggests that a prerequisite for the toxic action of zinc is entry into cells using channels that are shared with iron or calcium. This view was supported by experiments in which transferrin intensified the cytotoxic action of zinc in serum-free medium. Another agent facilitating zinc transport, prostaglandin E2, inhibited the proliferation of the B16 melanoma cell line. There were no conspicuous differences in zinc toxicity to pigmented and unpigmented cells. The toxic effect of zinc in the cell systems studied exceeded that of iron, copper, manganese and cobalt in the same concentration range. In vitro, Zn2+ should be regarded as a dangerous cation.
 ...
PMID:Cytotoxicity of zinc in vitro. 270 7

Hyperthermia has been combined with conventional radiation methods to achieve enhanced tumor destruction. We combined iodine 125 seeds with ferromagnetic thermoseeds in a single plaque to simultaneously deliver radiation and heat in a rabbit model of choroidal melanoma. Initially, six ferromagnetic thermoseeds were placed in parallel on a 14-mm episcleral plaque. The plaques were placed on normal rabbit eyes and on eyes containing transvitreally implanted choroidal melanoma. The heating response was assessed in both normal and tumor-containing eyes. Rigid copper-constantan and flexible Baily thermocouples were used to monitor temperature responses. The animals were subjected to an electromagnetic field of 100 kHz, with power of 1100 to 1500 W. The thermoseeds autoregulated at 48.2 degrees C. Scleral temperatures stabilized at 45.8 degrees C +/- 0.4 degrees C (SD), while temperatures at the base of the tumor stabilized at 43.6 degrees C +/- 0.1 degrees C. Ferromagnetic thermoseeds were then combined with iodine 125 seeds. Similar temperature responses were recorded, and autoradiographic findings confirmed a uniform radiation distribution. Varying the amount or type of ferromagnetic material in the thermoseeds allows the delivery of heat at virtually any temperature. Ferromagnetic hyperthermia may provide a more simplified approach over currently available methods of heat delivery.
 ...
PMID:Ferromagnetic hyperthermia and iodine 125 brachytherapy in the treatment of choroidal melanoma in a rabbit model. 280 4

The phenomenon of an elevated copper concentration in melanoma tumors was examined. It was demonstrated that 50-60% of total tissue copper is associated with metallothionein. The amino acid composition, electronic absorption and fluorescence were identical to that of the many known vertebrate Cu-thioneins. The immunological identification of melanoma tissue metallothionein was successful. The elevated Cu-thionein concentration in melanoma tumor tissue is not yet understood. It appears to be a common concept that in most tumors transient changes of the copper status parallel the metallothionein levels.
 ...
PMID:Copper-thionein in melanoma. 280 82

The toxicity and selectivity of 3,4-dihydroxybenzylamine (DHBA), an experimental antimelanoma agent that cannot enter the melanin pathway, broadly paralleled that of L-dopa in a panel of human melanoma cell lines sensitive or resistant to the latter drug. A human retinoblastoma cell line was found to be sensitive to both compounds. The toxicity and selectivity of both catechols were associated with inhibition of DNA synthesis; DHBA was more potent yet allowed a much greater degree of recovery compared with an equitoxic level of dopa. Dopa and DHBA had similar, dose-dependent effects on the cell cycle, arresting cells in S phase at low doses and in G1 at high doses. Replication of the DNA virus adenovirus was found to be inhibited by both agents. There was no difference between sensitive and resistant cell lines in the manganese or copper/zinc forms of superoxide dismutase, or in iron content and iron-binding capacity. Catechol toxicity was inhibited by the hydrogen peroxide scavenging agents pyruvate and methaemoglobin. Sensitivity to catechols did not correlate with melanin or tyrosinase content, rate of incorporation of tyrosine or dopa, intracellular levels of phenylalanine or tyrosine, or binding of a new monoclonal antibody directed against a melanosomal protein. These results indicate that DHBA and dopa exhibit selective toxicity for neural crest tumor cells independently of the melanisation pathway and of the superoxide scavenging system.
 ...
PMID:Melanin synthesis and the action of L-dopa and 3,4-dihydroxybenzylamine in human melanoma cells. 290 84

Challenge of human or murine melanoma cells with sodium arsenite, heavy metals (Zn2+, Cu2+ and Cd2+), or thiol-reactive agents (p-chloromercuribenzoate and iodoacetamide) induced the synthesis of four stress proteins with molecular masses of 100, 90, 72 (a doublet), and 32 (human) or 34 (murine) kDa. Enhanced expression of the 32- and 34-kDa polypeptides (p32 and p34) preceded or paralleled the synthesis of the other stress proteins. Hyperthermia, the calcium ionophore A23187, and amino acid analogs (L-azetidine-2-carboxylic acid and L-canavanine) induced the formation of the major stress proteins, but failed to increase synthesis of p32 and p34. Characterization of the dose and time dependence of p32 and p34 synthesis in human (A375) and murine (B16-F10) melanoma cells, respectively, indicated that these proteins were subject to similar regulatory mechanisms. Electrophoretic analysis of stressed cells pulsed with different metabolic precursors revealed that p32 and p34 were radiolabeled with [35S]methionine or 3H-amino acids but not by [3H]mannose or [35S]cysteine. Polyclonal antibodies raised against human p32 cross-reacted with murine p34. These data suggest that p32 and p34 are closely regulated human and murine gene products, respectively, whose synthesis can be modulated by thiol-reactive reagents. Induction of p32 and p34 by these agents, but not by heat shock, suggests that these proteins are a subset of stress-inducible gene products.
 ...
PMID:Induction of 32- and 34-kDa stress proteins by sodium arsenite, heavy metals, and thiol-reactive agents. 309 79

The B16/C3 murine melanoma is a pigmented tumor that is rich in the copper-containing enzyme, tyrosinase. This enzyme, which converts tyrosine to melanin precursors, is largely associated with membrane fractions of cells and exists in a number of discrete isozymic forms ranging in molecular mass from 58,000 to 150,000 daltons and pI from 3.4 to 5.2. One of these isozymes (Mr = 58,000, pI 3.4) has been purified to homogeneity. The purified enzyme catalyzes the hydroxylation of L-tyrosine to L-dihydroxyphenylalanine (L-DOPA) and the conversion of L-DOPA to dopaquinone. Ascorbic acid, tetrahydrofolate, and dopamine can serve as cofactors in the hydroxylase reaction. The Michaelis constants for the purified enzyme were 7 X 10(-4) M for L-tyrosine and 6 X 10(-4) M for L-DOPA. The Vmax for L-DOPA was much greater than the Vmax for L-tyrosine indicating that tyrosine hydroxylation is rate-limiting in melanin precursor biosynthesis. Two putative copper chelators, phenylthiourea and diethyldithiocarbamide inhibited both the tyrosine hydroxylase and L-DOPA oxidase activities of the enzyme. Phenylthiourea was a noncompetitive inhibitor while diethyldithiocarbamide was a competitive inhibitor indicating that these agents act by different mechanisms. When digested with proteases and glycosidases, higher molecular weight forms of tyrosinase co-migrated with the purified enzyme in isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggesting that the isozyme was derived from larger precursors. Thus, post-translational processing of tyrosinase may underlie isozyme diversity and this may be important in the control of melanogenesis in this tumor model.
 ...
PMID:Tyrosinase isozyme heterogeneity in differentiating B16/C3 melanoma. 309 4

This paper reports the effect of Cu(II) supplementation on the tyrosinase isozymes from Harding-Passey mouse melanoma. The dopa-oxidase activity of the microsomal and soluble isozymes is increased by incubation with Cu(II), whereas the activity of the unique 'in vivo' melanin-forming isozyme, bound to melanosomes, is not. Other divalent cations are ineffective in increasing the dopa-oxidase activity of tyrosinases. These results indicate the existence of a mixture of tyrosinase and apotyrosinase in the cytosol of melanocytes before reaching the melanosome. The paucity of Cu(II) in the cytosol could be one of the mechanisms of regulation contributing to avoid the formation of melanin outside the melanosome. Some kinetic characteristics of the enzymatic reconstitution of soluble and microsomal isozymes by Cu(II) are also studied, and the results suggest that the glycosylation of apotyrosinase during its maturation yields a conformational change favouring the binding of Cu(II) at the enzyme active site, by lowering the activation energy of the reconstitution reaction.
 ...
PMID:The existence of apotyrosinase in the cytosol of Harding-Passey mouse melanoma melanocytes and characteristics of enzyme reconstitution by Cu(II). 310 92

A number of transition metal ions with a wide distribution in biological systems, e.g., Cu2+, Co2+ and Zn2+, are shown to affect markedly the chemical properties of melanins formed by the tyrosinase-catalysed oxidation of dopa. Acid decarboxylation and permanganate degradation provide evidence that melanins prepared in the presence of metal ions contain a high content of carboxyl groups arising from the incorporation of 5,6-dihydroxyindole-2-carboxylic acid (DICA) into the pigment polymer. Naturally occurring melanins from cephalopod ink and B16 mouse melanoma were found to be much more similar to melanins prepared in the presence of metal ions than to standard melanins prepared in the absence of metal ions. These results suggest that the presence of carboxylated indole units in natural melanins is probably due to the intervention in the biochemical pathway of metal ions which, as recently shown, catalyse the formation of DICA versus 5,6-dihydroxyindole in the rearrangement of dopachrome.
 ...
PMID:Structural modifications in biosynthetic melanins induced by metal ions. 312 88

Using human tyrosinase cDNA as a probe, a mouse tyrosinase cDNA clone representing approximately 75% of the tyrosinase coding region and a mouse genomic clone which includes the tyrosinase 5' coding sequences were isolated: nucleotide and deduced amino acid sequence of the mouse tyrosinase gene were determined from these clones. The predicted amino acid sequence revealed that the mouse tyrosinase is composed of 533 amino acids with a molecular weight of 60,536. The deduced protein contains 6 potential N-glycosylation sites, two cysteine- and two histidine-rich regions which may serve as copper-binding sites, a potential signal and transmembrane sequences. The mouse and human tyrosinase nucleotide and deduced amino acid sequences are approximately 81% homologous. The level of mouse tyrosinase mRNA was elevated after stimulation of Cloudman S-91 melanoma cells with melanotropin and isobutylmethylxanthine and the level of transcript reflected that of tyrosinase activity and melanin content in the cells.
 ...
PMID:Sequence analysis of mouse tyrosinase cDNA and the effect of melanotropin on its gene expression. 313 20


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>