Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lysosomal enzyme beta-hexosaminidase and the melanocyte specific enzyme tyrosinase were examined in human melanoma cell cultures. The beta-hexosaminidase activity of the medium was approximately 40% of the total cellular activity after 24 h, while after 48 h the activity in the medium was twice that of the cells. The tyrosinase activity in the medium was 5% and 19% of the total cellular activity after the 24 h and 48 h incubation, respectively. The low level of lactate dehydrogenase activity in the medium after 24 as well as 48 h of incubation indicated that the release of beta-hexosaminidase and tyrosinase was not due to membrane injury. The data suggest, that 1) beta-hexosaminidase may be a candidate for tumor markers in malignant melanoma, and 2) the tyrosinase activity found in sera of melanoma patients may be due, at least partly, to enzyme release by living cancer cells.
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PMID:Enzyme release from cultured human melanoma cells. 197 50

Beagle serum proteins were separated by polyacrylamide gel electrophoresis (PAGE) and the electrophoretograms were examined by one- and two-dimensional analyses with a laser densitometer. In order from the anodic side of the PAGE pattern, pre-albumin, hexokinase, tyrosinase, alkaline phosphatase, urease, and aldehyde dehydrogenase were assumed to be present based on Rf and Mw. Serum albumin, lactate dehydrogenase, and catalase appeared to be present based on a comparison of their electrophoretic mobility with that of protein standards of known Mw. Verification of beagle serum protein fractions by immunofixation electrophoresis and western blotting electrophoresis, with rabbit anti-human serum, indicated alpha 1-antitrypsin, albumin, haptoglobin, ceruloplasmin, C3c complement, IgG, and IgA. Serum protein fraction values (%) obtained by one- and two-dimensional analyses were similar.
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PMID:Analysis of a polyacrylamide gel electrophoretogram of beagle serum protein by laser densitometer. 765 Sep 2

Paralogy is a pervasive problem in trying to use nuclear gene sequences to infer species phylogenies. One strategy for dealing with this problem is to infer species phylogenies from gene trees using reconciled trees, rather than directly from the sequences themselves. In this approach, the optimal species tree is the tree that requires the fewest gene duplications to be invoked. Because reconciled trees can identify orthologous from paralogous sequences, there is no need to do this prior to the analysis. Multiple gene trees can be analyzed simultaneously; however, the problem of nonuniform gene sampling raises practical problems which are discussed. In this paper the technique is applied to phylogenies for nine vertebrate genes (aldolase, alpha-fetoprotein, lactate dehydrogenase, prolactin, rhodopsin, trypsinogen, tyrosinase, vassopressin, and Wnt-7). The resulting species tree shows much similarity with currently accepted vertebrate relationships.
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PMID:Extracting species trees from complex gene trees: reconciled trees and vertebrate phylogeny. 1063 Oct 44

Allozyme spectra of peroxidase, esterase, superoxid dismutase, tyrosinase, alcohol dehydrogenase, lactate dehydrogenase, and acid phosphatase were examined in populations of sexual (Taraxacum serotinum and Pilosella echioides) and apomictic (T. officinalis and P. officinarum) plant species. The heterozygosity in these populations (0.455-0.620) proved to be considerably higher than the average level characteristic of plant populations (0.058-0.185). The populations examined did not differ in the mean phenotype number mu, i.e., they exhibited the same diversity (3.213-3.380). The proportion of rare phenotypes h also did not differ between the sexual and apomictic species of the same genus, whereas this parameter in the Pilosella populations (0.150-0.174) was significantly higher than in the Taraxacum ones (0.093-0.114). The populations were characterized by numerous isozyme spectra (more than 11 per populations) and displayed multiple allelism (the mean allele frequency was 3.63-4.38 per locus). They exhibited a high percentage of rare (occurring at a frequency lower than 5%) spectra (35-80%). This indicates that agamic complexes, to which these populations belong, may have a more complicated genetic structure of both apomictic and sexual populations than the species that do not belong to agamic complexes.
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PMID:[Allozyme variation in sexual and apomictic Taraxacum and Pilosella (Asteraceae) populations]. 1581 Jun 10

The search is on for biomarkers for use in the diagnosis, staging, prognosis, and management of patients with melanoma. As with many types of cancer, the hematogenous spread of melanoma is a bad prognostic sign, and many groups have attempted to detect circulating melanoma cells in patients with different stages of melanoma. Some studies have used direct extraction of intact tumor cells from the peripheral blood and others the detection of surrogate markers of circulating melanoma cells, such as tyrosinase or MART-1. However, a correlation between the detection of intact melanoma cells in the circulation and prognosis is controversial. Many other biomarkers have also been studied, including lactate dehydrogenase, S100, TA90, and C-reactive protein. Much progress has been made, and preliminary studies have shown promise with many of these markers. Finally, the detection of tumor-specific circulating DNA has shown promise as a prognostic and diagnostic marker of disease in melanoma as well. In this review we examine the most promising biomarkers for use in patients with cutaneous melanoma.
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PMID:Tumor cell and circulating markers in melanoma: diagnosis, prognosis, and management. 1609 Dec

This study was conducted to examine the prognostic impact of four biomarkers [tyrosinase and MART-1 messenger RNA (mRNA), S100beta protein and lactate dehydrogenase (LDH)] in patients with metastatic melanoma, together with established clinical factors. Tyrosinase and MART-1 mRNA were measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). S100beta was measured using a commercially available immunoassay, and LDH was analysed conventionally. All markers were measured in blood samples before interleukin-2-based immunotherapy in 85 patients with metastatic melanoma. LDH, S100beta, tyrosinase, number of metastatic sites, location of metastatic sites and performance status were all significant factors for survival in univariate analyses. In multivariate analysis, tyrosinase [hazard ratio (HR)=1.6; 95% confidence interval (CI), 1.1-2.6; P=0.04] and LDH (HR=2.0; 95% CI, 1.1-3.5; P=0.02) were both independent prognostic factors for survival. A combination variable of tyrosinase and LDH remained independently associated with survival (P=0.04) after adjusting for the American Joint Committee on Cancer (AJCC) stage IV classification in a multivariate analysis involving both models. It can be concluded that tyrosinase mRNA and elevated LDH are independent prognostic factors for poor survival in this group of 85 patients. Additional studies are needed before the prognostic value of tyrosinase mRNA in metastatic melanoma can be firmly established. Further evaluation of the combined measurement of tyrosinase mRNA and LDH is warranted.
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PMID:Tyrosinase messenger RNA in peripheral blood is related to poor survival in patients with metastatic melanoma following interleukin-2-based immunotherapy. 1617 68

High sensitivity differential scanning calorimetry (HSDSC) has been used to study the interaction of the model proteins lactate dehydrogenase (LDH) and tyrosinase with dimyristoylphosphatidylcholine (DMPC) liposomes, and relate this to the thermal and physical stability of the proteins. On heating, both LDH and tyrosinase denatured irreversibly in a time-dependent manner and modified the phase transition behaviour of DMPC liposomes at all concentrations investigated. The most marked effects occurred for the pretransition rather than the main phospholipid phase transition. The effects on the bilayer are likely to result from electrostatic interactions of the hydrophilic proteins with the head-groups of DMPC molecules, whilst due to their hydrophilic nature they do not penetrate into the bilayer. Tyrosinase is more highly ionised than LDH at the pH of the investigation, which may explain why tyrosinase has a greater effect than LDH on the HSDSC scans at mg/ml protein concentrations.
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PMID:High sensitivity differential scanning calorimetry investigation of the interaction between liposomes, lactate dehydrogenase and tyrosinase. 1681 96

Although there is no routine procedure for determination of serum markers in patients with malignant melanoma (MM), some markers are being studied as potentially useful prognostic tools. Serum lactate dehydrogenase (LDH), protein S-100B, melanoma-inhibiting activity (MIA) and tyrosinase may correlate with melanoma progression. In this study, the results of determination of S100 protein, LDH, MIA and tyrosinase in the serum of 50 patients with MM (stages I-IV) were determined. The increased values of MIA were found in 26% patients in stage I, while in 50% patients in stage IV Increased S-100 protein was found in 13% patients in stage I while in 50% patients in stage IV. The increased values of LDH were found in 26% patients in stage I, while in 25% patients in stage IV. The positive serum tyrosinase was noticed in 17.3% patients in stage II, while in 25% patients in stage IV. The obtained results have revealed no significant differences between the groups in higher and lower stages of the disease, indicating that blood markers are not reliable prognostic factors for MM progression.
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PMID:Results of the determination of serum markers in patients with malignant melanoma. 1746 41

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

Melanoma is the most malignant type of all skin neoplasms. Its worldwide incidence has steadily increased during the past decades, suggesting a probable melanoma 'epidemic'. Although current clinical, morphologic, and histopathologic methods provide insights into disease behavior and outcome, melanoma is still an unpredictable disease. Once in an advanced stage, it remains a disastrous affliction with scarce therapeutic options. Therefore, significant efforts need to be made in finding informative biomarkers or surrogate markers that could aid or improve early diagnosis of melanoma, its correct staging, the discrimination of other pathological conditions as well as indicate patients' prognosis or the most appropriate therapeutic regimes. Ideally these markers are secreted into body fluids and easily amenable to the design of non-invasive clinical tests. A critical view on the current debate on serologic protein markers, e.g., lactate dehydrogenase, tyrosinase, and melanoma inhibiting activity, and some selected non-protein markers, e.g., 5-S-cysteinyl-dopa and circulating nucleic acids, will be offered and novel innovative approaches currently being explored will be discussed. Special emphasis is put on the S100 family of calcium binding proteins that is more and more emerging as a potentially important group of both molecular key players and biomarkers in the etiology, progression, manifestation, and therapy of neoplastic disorders, including malignant melanoma. Notably, S100B and, possibly, other S100 proteins like S100A4 are assumed to fulfill requirements which make them strong biomarker candidates in melanoma. Moreover, S100 proteins receive attention as possible targets of therapeutic intervention moving closer to clinical impact.
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PMID:Protein and non-protein biomarkers in melanoma: a critical update. 2305 20


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