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

Phenotypic heterogeneity is a characteristic feature of tumor lesions in patients with melanoma. Variability can be observed in cell morphology, pigmentation, and antigen expression. To test whether phenotypic heterogeneity could be the result of events regulated during cell differentiation, we evaluated the expression of a panel of differentiation traits on melanoma cells. Metastatic melanoma lesions from two patients, designated FD and AP, were examined histologically and found to contain mixed populations of cells. Established melanoma cell lines derived from each of these lesions were subcloned at early passage in culture (passages 7 and 8) to create a panel of clones derived from each tumor. There was heterogeneity in the expression of differentiation-related traits in clones, corresponding to distinct phenotypes observed within the original tumors. Clones from patient FD corresponded to early to intermediate stages of melanocyte differentiation, and clones from patient AP ranged from intermediate to late stages. The influence of cholera toxin and PMA on differentiation of parental cultures and subclone was studied. Results of induction studies demonstrated a number of features of differentiation of melanoma cells: regulation of differentiation traits is coordinated as a program of traits expressed sequentially at specific stages; early traits, such as the epidermal growth factor receptor and the melanoma chondroitin sulfate proteoglycan antigen, are downregulated as melanoma cells differentiate, whereas late markers, including melanin, tyrosinase activity, and antigens expressed in mature melanosomes, are upregulated; Ia (class II major histocompatibility) antigens are characteristically expressed on melanomas corresponding to early or intermediate stages of differentiation and are regulated as part of the differentiation program; minimal changes in stage of differentiation were observed during induction of parental cultures with either cholera toxin or PMA, whereas definite shifts in differentiation could be induced in selected cloned subpopulations. We conclude that melanoma cells are not frozen at a specific stage of differentiation, but rather are capable of differentiating when exposed to appropriate signals. Diversity in the differentiation state of melanoma cells can account for much of the phenotypic heterogeneity observed in melanoma lesions.
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PMID:Phenotypic heterogeneity of melanoma. Relation to the differentiation program of melanoma cells. 310 78

Antityrosinase antibody is a newly detected antibody in the sera of patients with melanoma or vitiligo. The serum level of the antibody is measured by enzyme-linked immunosorbent assay (ELISA). The autoantigen is tyrosinase itself, the enzyme that participates in pigment (melanin) formation by both melanocytes and melanoma cells Antityrosinase IgG antibodies were found to be present in high titers in sera of patients with vitiligo in comparison to patients with melanoma or healthy volunteers. The level of antityrosinase antibodies in patients with metastatic melanoma was significantly higher than the level in healthy subjects, but insignificantly higher than the level in patients with no evidence of disease. Patients with melanoma and MAH (melanoma-associated hypopigmentation; vitiligo-like) had the same level of antityrosinase antibodies as the controls or the patients with metastatic melanoma. This observation reflected the possible absorption of antityrosinase antibodies by melanoma antigens, and pointed to the participation of the antibodies in the destruction of normal melanocytes in patients with melanoma, as part of the immune reaction towards this disease. The most interesting observation was the high level of antityrosinase antibodies in patients with vitiligo in comparison with the low level in patients with melanoma, patients with MAH, and patients with NED. Although the cutaneous manifestations of vitiligo and MAH are similar and result from destruction of melanocytes by specific antibodies, the two situations are immunologically different. The serum level of free antityrosinase antibodies could not serve as marker for the state of the disease or disease progression or relapse, as no significant difference could be detected between the levels in patients without evidence of disease to those with metastatic melanoma; nor could the levels of antityrosinase antibodies differentiate between the different sites of the primary lesion. However, we have shown that antityrosinase antibodies could be used for monitoring the response to active specific immunotherapy by injection of anti-idiotypic antibodies mimicking the HMW-MAA. In the future, antityrosinase antibodies may be incorporated into immunotherapy for malignant melanoma.
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PMID:The clinical significance of antityrosinase antibodies in melanoma and related hypopigmentary lesions. 977 50

Adoptive transfer of tumor-infiltrating lymphocytes (TIL) is in development for the treatment of metastatic melanoma. In phase II clinical trials, patients with metastatic melanoma that received TIL after preconditioning had a 50-70% clinical response rate. The current approach to generate TIL is to culture melanoma enzyme digests in the presence of IL-2 for a 10- to 20-day period followed by 2 weeks of rapid expansion (REP). Prior to administration, cell therapies are characterized and tested for purity. TIL are characterized by CD3 surface marker expression, and purity is assessed by the amount of tumor remaining in culture. Evaluating TIL purity has traditionally been done by immunohistochemistry, which is often considered semiquantitative. To generate a quantitative assay, we used multiparameter flow cytometry to evaluate the presence of viable tumor cells by staining TIL populations with a viability dye and an antibody cocktail that detects intracellular tumor-antigens gp100, Mart-1, tyrosinase, S100, and surface tumor-antigen melanoma chondroitin sulfate proteoglycan (MCSP), and CD3 on T cells. Tumors were identified by gating on the viable CD3(-) population. Antigens in tumors were initially optimized with individual antibodies using both immunohistochemistry and flow cytometry. When eight different tumor cell lines were spiked into an activated T cell culture, flow cytometry was able to distinguish lymphocytes from tumors in all samples tested. Most importantly, the assay was able to detect melanoma cells in all enzyme digests (9/9) from patient samples. After IL-2-induced TIL expansion, there was a significant decrease in tumor cells; tumor cells were detected in only 2 of 12 samples. In eight IL-2-induced TIL samples that were further expanded in REP, no tumor cells were detected. We have demonstrated that flow cytometry is an alternative to immunohistochemistry for defining the purity of a TIL population.
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PMID:Flow cytometry assessment of residual melanoma cells in tumor-infiltrating lymphocyte cultures. 2246 96