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 reactivity in an avidin-biotin complex immunoperoxidase reaction with a large panel of anti-human melanoma associated antigen (MAA) and anti-HLA monoclonal antibodies of 24 primary and 11 metastatic acral lentiginous melanoma (ALM) lesions was compared to that of 12 primary and 12 metastatic nodular melanoma (NM) lesions. The expression of the membrane bound vitronectin receptor, Mr 110,000 MAA, Mr 97,000 MAA, and intercellular adhesion molecule-1 was significantly lower in both primary and metastatic ALM lesions than in their NM counterparts. Furthermore, primary ALM lesions displayed a significantly lower expression than primary NM lesions of the membrane bound high molecular weight melanoma associated antigen (HMW-MAA), Mr 110,000 MAA, Mr 100,000 MAA, 9-O-acetyl-GD3, GD2-GD3, and GD2, of the cytoplasmic monoclonal antibody 465.12 defined MAA and of transferrin receptor and of HLA-DQ and DP antigens; ALM metastases expressed a significantly lower level of carcinoembryonic antigen-MAA than NM metastases. These antigenic differences do not reflect an antigenic paucity of ALM cells, since ALM lesions express a higher level of T4-tyrosinase than NM lesions and a level of HLA Class I antigens similar to that of NM lesions. In view of the use of HMW-MAA, Mr 97,000 MAA, and GD3 in immunoscintigraphy and/or in immunotherapy, it is noteworthy that the three antigens are expressed in a similar high percentage of ALM metastases and of primary and metastatic NM lesions, while the HMW-MAA is expressed in a markedly lower percentage of primary ALM lesions than Mr 97,000 MAA and GD3. However, the degree of heterogeneity of HMW-MAA within a positive primary ALM lesion, as measured by the percentage of stained melanoma cells, is lower than that of Mr 97,000 MAA and GD3. The expression of the antigens investigated in ALM and NM lesions was not correlated with the presence of lymphocyte infiltrates, melanin content of melanoma cells, and epithelioid and spindle type of melanoma cells in the lesions. On the other hand, the survival of patients with ALM was inversely correlated with the expression of intercellular adhesion molecule 1 or HMW-MAA in their primary lesions. A potential role of HMW-MAA in the course of the disease is suggested by its significantly higher expression in metastatic than in primary ALM lesions.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differential expression of melanoma associated antigens in acral lentiginous melanoma and in nodular melanoma lesions. 167 29

Since response rates in human melanoma are low with currently available therapeutic modalities, we have reevaluated the potential usefulness of retinoids as new alternatives for therapy of metastatic melanoma. Nine synthetic retinoids with high affinity and/or selectivity for the retinoic acid receptors (RAR) alpha, beta, and gamma were studied in comparison to all-trans retinoic acid (RA) for their in vitro effects on melanoma cell proliferation and for their immunomodulating capacities using four human melanoma cell lines. Eight out of ten retinoids tested had no effect on melanoma cell growth, whereas the remaining two compounds with high RAR-gamma selectivity (CD437 and CD2325) showed a dose-dependent antiproliferative effect on all melanoma cell lines with IC50 (concentration inhibiting response by 50%) values between 10(-6) and 10(-7)M. Further analyses showed that paracrine-mediated tumor cell growth inhibition such as induction of transforming growth factor (TGF)-beta described as one mechanism of retinoid action and enzyme systems such as tyrosinase and monoamine oxidase were not involved in mediating the antiproliferative effects exerted by the two retinoids. Four of nine retinoids modulated HLA-DR expression on human melanoma cells, and expression levels of intercellular adhesion molecule 1 (ICAM-1) was increased by another subset of compounds. These effects were, however, not correlated to the receptor selectivity of the retinoids. The potent growth inhibitory effect of the RAR-gamma-selective retinoids and the immunomodulating capacities of the retinoids open an interesting alternative for new antiproliferative and immunomodulatory strategies in the treatment of metastatic melanoma.
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PMID:Effects of various synthetic retinoids on proliferation and immunophenotype of human melanoma cells in vitro. 759 89

Expression of HLA class I molecules is essential for the recognition of tumor cells by CD8+ T cells. In this study, 48 bioptic samples of 42 patients in all stages of melanoma were investigated after short-time cultivation of tumor cells. To confirm melanocytic origin of cultured cells, samples were screened for mRNA expression of melanoma markers gp100, tyrosinase, MAGE-3, MelanA, and MUC18 by reverse transcriptase-polymerase chain reaction. Surface expression of specific HLA-A and -B allospecificities on melanoma cells were analyzed with a standard microcytotoxicity assay after stimulation with interferon (IFN)-alpha and compared with the background found in peripheral blood mononuclear cells from the corresponding patients. Immunohistochemistry and flow cytometry confirmed specific losses in cases where the appropriate monoclonal antibodies were available. The level of expression of HLA-I, HLA-II, and intercellular adhesion molecule 1 antigens on melanoma cells cultured in the presence or absence of IFN-alpha and IFN-gamma was determined cytofluorometrically. All cell cultures tested were found to be positive for one or more melanocytic markers by reverse transcriptase-polymerase chain reaction. The specific HLA-I alleles on the cultured cells were detectable in 45 of 48 samples. In 11 cases a specific loss of one HLA-I allele was observed (2 x A2, B7, B8, B18, 4XB44, B47, B49). Ten of these samples were derived from locoregional lymphnode metastases or from distant metastatic tumors. Only one sample from a primary melanoma showed a specific loss of HLA-I (B47). IFN-alpha upregulated expression of HLA-I up to 4-fold. IFN-gamma enhanced the appearance of HLA-II up to 35-fold and the expression of intercellular adhesion molecule 1 up to 40-fold. Selective loss of HLA-I allospecificities might be a major step in tumor progression.
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PMID:Higher frequency of selective losses of HLA-A and -B allospecificities in metastasis than in primary melanoma lesions. 974 Feb 47