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)

We have previously shown that small B16 melanomas can be successfully treated using a combination of anti-cytotoxic T lymphocyte antigen (CTLA)-4 monoclonal antibody with a granulocyte/macrophage colony-stimulating factor (GM-CSF) producing irradiated tumor cell vaccine. Regression of tumors results in long-lasting immunity and is frequently accompanied by autoimmune depigmentation. Here we examine the cellular and molecular mechanisms of this combined treatment. Histological examination of depigmented lesions revealed infiltration of polymorphonuclear cells and deposition of antibody. The combination therapy also induced tumor rejection and skin depigmentation in B cell-deficient and in CD4(+) T cell-depleted mice. Both effects of the treatment absolutely required CD8(+) T cells. Analysis of the response in successfully treated mice revealed elevated levels of CD8(+) T cells specific for a nonameric peptide consisting of residues 180-188 of the melanocyte differentiation antigen tyrosinase-related protein (TRP)2. There was no evidence of reactivity to the melanocyte antigens gp100, tyrosinase, Mart1/MelanA, or TRP1. Fas-FasL interactions and perforin played a role in mounting the effector response, whereas the tumor necrosis factor pathway was not required. The cellular requirements for tumor rejection in this therapeutic setting were strikingly different from those in a prophylactic setting. In particular, if mice received a prophylactic vaccine consisting of anti-CTLA-4 and B16-GM-CSF before tumor challenge, full protection was obtained even in the absence of CD8(+) T cells. Our data demonstrate that therapeutic autoreactive CD8(+) T cell responses can effectively be generated in tumor-bearing mice and stresses the value of studying tumor immunity in a therapeutic rather than a prophylactic setting.
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PMID:Elucidating the autoimmune and antitumor effector mechanisms of a treatment based on cytotoxic T lymphocyte antigen-4 blockade in combination with a B16 melanoma vaccine: comparison of prophylaxis and therapy. 1151 4

A number of single gene mutations in laboratory mice produce hair follicle defects resulting in deformed hair shafts. The radiation-induced (SB/LeJ-Foxq1(sa)) satin mutant mice have a satin-like sheen to their hair and dilute colouration. This sheen is due to failure of the hair shafts to develop normal medullas, while the pigment dilution is due to the unrelated beige (lysosomal trafficking regulator, Lyst(bg)) mutation. A new allelic mutation, Foxq1(sa-J), arose spontaneously on the albino (tyrosinase, Tyr(c)) MRL/MpJ-Fas(lpr) background. The Foxq1(sa-J) allele has a C to T transition at position 490. By contrast, the Foxq1(sa) mutant allele was confirmed to be a 67 base pair deletion followed by two base changes (GA to AT). Morphologic changes were similar to those seen in Hoxc13 transgenic and targeted mutant mice. This new allelic mutation provides yet another tool to investigate formation of the interior structures of hair shafts.
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PMID:R164C mutation in FOXQ1 H3 domain affects formation of the hair medulla. 2348 30