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)

In 19 patients with malignant melanoma of the choroid and 11 controls 20 different metabolic parameters of melanin and melatonin metabolism in urine were examined by high-pressure liquid chromatography (HPLC). Significant differences were found in DOPA, DOPAC, MHPG, alpha-keto-glutaric acid, pseudo-uridine, serotonin, OH-tryptophan and homovanillic acid.
 ...
PMID:[HPLC detection of pathologic metabolites of melanin and melatonin metabolism in the urine in malignant melanoma of the choroid]. 376 75

Tyrosine countertransport was used to demonstrate the existence of a carrier system for neutral amino acids in the lysosomal membrane of FRTL-5 thyroid cells. In addition to tyrosine, the carrier system recognized the neutral amino acids leucine, histidine, phenylalanine, and tryptophan. Cystine and lysine, amino acids for which a lysosomal carrier system has been demonstrated, showed no competition with tyrosine for countertransport. The tyrosine system showed stereospecificity and cation independence. It did not require an acidic lysosome or the availability of free thiols. The apparent Km for tyrosine was approximately 100 microM; the energy of activation of the system was approximately 9.7 kcal/mol. This new lysosomal membrane carrier system for neutral amino acids resembles the plasma membrane L system in 3T3 Chinese hamster ovary cells and melanoma B-16 cells.
 ...
PMID:Characteristics of a lysosomal membrane transport system for tyrosine and other neutral amino acids in rat thyroid cells. 378 56

The purification of two isoenzymes of tyrosinase has been carried out in Harding-Passey mouse melanoma. One is found in the cytosol and the other one bound to melanosomes. Both migrate as single bands on sodium dodecyl sulphate/polyacrylamide gels, having an apparent Mr of 58 000. Solubilized particulate tyrosinase showed an aggregation equilibrium involving a monomer, tetramer, octamer and a high-Mr micellar form with Brij 35, the solubilizing agent. H.p.l.c. studies indicated a interconversion between those species, the monomer contribution increasing with the sample dilution. The tetramer and the octamer probably represent the predominant forms in vivo. Soluble tyrosinase showed a simpler aggregation equilibrium, involving two forms, monomer and tetramer, with the same interconversion pattern. Fluorescence studies suggested that tryptophan residues were exposed to the aqueous environment when tyrosinase was dissociated by dilution. Tyrosinase shows a tendency to aggregate, at low protein concentration, and a resistance to dissociation by urea or SDS so remarkable that gel-permeation chromatography in 4M-urea does not affect the equilibrium, and the band obtained on SDS/polyacrylamide-gel electrophoresis is a dimer.
 ...
PMID:Aggregation equilibria of tyrosinase of Harding-Passey mouse melanoma. 392 35

The role of L-tyrosine, L-phenylalanine, L-dihydroxyphenylalanine (dopa) and L-tryptophan in melanin biosynthesis in melanotic hamster melanoma IC-Sofia was investigated with the aid of 14C-aminoacids. Tyrosine and phenylalanine were found to be the main melanin precursors: about 64.5% of total melanin labeling was due to tyrosine incorporation and 27.4% to phenylalanine incorporation. Negligible proportions of melanin radioactivity (5.7% and 2.4%, respectively) resulted from dopa and tryptophan utilization in melanin synthesis. The involvement of each of the aminoacids under investigation in melanin synthesis in vivo is discussed.
 ...
PMID:Aminoacids--precursors of melanin synthesis in hamster melanoma. 651 10

Tryptophan metabolism has been studied in mice with Harding-Passey melanoma and in controls, after a load of 1.0 g/kg b.w. of L-tryptophan by determining ten urinary metabolites of the kynurenine pathway and some enzyme activities involved in the degradation of this aminoacid. Kynurenine was the only tryptophan derivative excreted in significantly higher quantities in mice with melanoma with respect to the controls. This result is in agreement with a significantly higher activity of hepatic tryptophan pyrrolase in mice with melanoma. Liver kynureninase and liver and kidney kynurenine aminotransferase activities were similar in the two groups of mice. These findings point to a possible role of tryptophan in the biogenesis of melanins in pathological conditions such as in melanoma.
 ...
PMID:Enzyme activities and metabolites along the kynurenine pathway in mice with Harding-Passey melanoma. 686 53

1. Linear uptake of tyrosine lasted for 1 min in cultured B-16 mouse melanoma cells preloaded with an amino acid such as tyrosine. 2. The tyrosine uptake increased markedly on preincubating the cells with 0.1 mM methionine, tyrosine, histidine or tryptophan and moderately with 1 mM phenylalanine, valine, isoleucine, or leucine. The effects of the preincubation on leucine uptake were similar to those on tyrosine uptake. 3. The tyrosine uptake was Na-independent under the experimental conditions used (0.05-1.0 mM); Km 75 micrometers and Vmax 15 nmol/min/mg protein. The methionine uptake (0.1-0.5 mM) was also Na-independent (Km 150 micrometers and Vmax 25 nmol/min/mg protein), whereas Na-dependent uptake could contribute at 2 mM methionine. 4. Inhibitions of tyrosine uptake by tryptophan, phenylalanine, leucine, isoleucine, methionine, valine, and histidine were competitive, giving K1 values of 70, 80, 100, 130, 160, 350, and 900 micrometers, respectively. 5. Exchange between intracellular methionine and extracellular tyrosine and vice versa was equimolar. Potencies of amino acids in stimulating tyrosine efflux were in the following order: methionine greater than tyrosine greater than histidine greater than tryptophan greater than phenylalanine greater than leucine greater than isoleucine much greater than valine. 6. The amino acid affinity of the system in the intracellular surface was suggested to be different from that in the extracellular surface. 7. The theophylline-treated cells showed a marked increase in tyrosine-uptake rate with elevated Vmax and unchanged Km.
 ...
PMID:Studies on the transport of tyrosine, leucine, and methionine in cultured B-16 mouse melanoma cells. 713 Jan 45

We have developed a routine capillary gas-chromatographic profiling method for simultaneous quantitative determination of the tert-butyldimethylsilyl derivatives of homovanillic acid, vanilmandelic acid, 3-methoxy-4-hydroxyphenylethylene glycol, and 3,4-dihydroxyphenylacetic acid and the estimation of 5-hydroxyindole-3-acetic acid in urine. The method is useful for diagnosis and followup of patients with functional tumors characterized by increased urinary excretion of metabolites originating from the metabolism of tyrosine and tryptophan--e.g., neuroblastoma, pheochromocytoma, carcinoid, and melanoma. It may also be applicable in pharmacokinetic studies of administered aromatic amino acids (parkinsonism, mental diseases, loading tests) and for diagnosis and followup of patients with inborn errors of metabolism that are characterized by organic aciduria (for instance, tyrosyluria and phenylketonuria).
 ...
PMID:Simultaneous determination of the four major catecholamine metabolites and estimation of a serotonin metabolite in urine by capillary gas chromatography of their tert-butyldimethylsilyl derivatives. 746 Feb 71

Expression systems were developed for evaluating recombinant human thrombomodulin (TM) production in different host cell lines by investigating the performance of five mammalian expression vectors. The expression vectors were constructed so that they contain multiple monocistronic gene cassettes which include a gene encoding a dominant selectable marker, HyR (hygromycin B phosphotransferase), under the regulation of the thymidine kinase promoter, the target gene which encodes a truncated human re-TM under the regulation of various promoters, an amplifiable gene (Dhfr) encoding murine dihydrofolate reductase under the regulation of either the SV40 early or late promoter along with the SV40 enhancer and the SV40 ori. We tested the performance of the five expression vectors in human embryonic kidney cells (HEK293), baby hamster kidney cells (BHK), human melanoma cells (CHL-1) and Dhfr- Chinese hamster ovary cells (CHO/Dhfr-). We found that the efficiency of DNA uptake, transient expression and stable expression of the different expression vectors were all cell-line dependent. However, the myeloproliferative sarcoma virus (MPSV) LTR promoter consistently showed higher expression levels in all cell lines, particularly in HEK293 cells. These results were confirmed by the distribution curves of the level of expression of individual clones. Furthermore, by amplifying Dhfr in transfected CHO/Dhfr- cells with 100 nM methotrexate, we achieved a 20-fold increase in re-TM production using the SV40 late promoter to control murine Dhfr expression. Our data from DNA and mRNA analysis reveal that pMPSV-TM has a high transcription efficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Expression efficiency of the human thrombomodulin-encoding gene in various vector and host systems. 752 46

The human melanoma cell line M24met expresses tissue factor, the cellular initiator of the blood coagulation cascade. Blocking of the coagulation pathways at the level of tissue factor, factor Xa, or thrombin inhibits hematogenous M24met metastasis in SCID mice, implicating a role for thrombin generation in this process. Dependent on cell surface tissue factor activity, M24met cells generate thrombin in vitro. Thrombin and the thrombin receptor agonist peptide TRP-14 activate a signaling pathway in M24met cells that involves an increase in intracellular calcium and induces cell proliferation. Immunofluorescence evidences expression of the signaling thrombin receptor on these cells. Thus, M24met melanoma cells express both the initiating cell surface receptor for the coagulation pathways and the central signaling receptor of the coagulation system, suggesting the in situ generation of proliferative signals which can contribute to the malignant phenotype.
 ...
PMID:Tissue factor-initiated thrombin generation activates the signaling thrombin receptor on malignant melanoma cells. 771 65

Previous work demonstrated that alpha-thrombin promoted tumor cell adhesion to endothelium and extracellular matrix as well as enhanced the metastatic capacity of tumor cells. This study was initiated to investigate whether the thrombin effect on tumor cells is mediated through the "tethered ligand" thrombin receptor. RT-PCR analysis using primers based on the human thrombin receptors detected mRNA in human colon adenocarcinoma cells (clone A), whose authenticity was confirmed by Southern hybridization. The presence of thrombin receptor mRNA in rat (W256 carcinosarcoma) and mouse (melanoma) tumor cells was demonstrated by RT-PCR/Southern blotting using species-specific PCR primers. Sequencing of the PCR fragment of clone A cells revealed complete homology with the reported human cDNA sequence. Subsequently, tumor cells derived from three species, i.e., human, rat, and mouse, were found to express the thrombin receptor protein as revealed by immunoblotting using ligand peptide-derived mAb ATAP138, whose reactivity towards the M(r) approximately 66,000, potential thrombin receptor was blocked by preincubating the antibody with the immunogen peptide SFLLRNPNDKYEPF (TRP 14). Finally, peptides TRP 14 and TRP 7 (SFLLRNP), but not TRP 5 (FLLRN), were found to mimic alpha-thrombin in stimulating tumor cell adhesion to fibronectin, suggesting that the thrombin receptors expressed on solid tumor cells are biologically functional.
 ...
PMID:Solid tumor cells express functional "tethered ligand" thrombin receptor. 783 43


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