Tyrosinase (TYR) is a key enzyme in melanin biosynthesis and its activity is an important biomarker for dermatological disorders, such as vitiligo, melanoma and actinic damages.
Herein, we show that a large fraction of the human melanoma epitope tyrosinase reactive TCR transduced T cells that exhibit effector memory (TEM) phenotype and undergo programmed necrosis, or necroptosis, upon TCR restimulation.
NFATc2(+/Hi) melanoma cell lines were CD271(+) and deficient for expression of melanocyte differentiation antigens (MDAs) MART-1, gp100, tyrosinase and of GPNMB, PGC1-α and Rab27a, all regulated by MITF.
Structural insight with mutational impact on tyrosinase and PKC-β interaction from Homo sapiens: Molecular modeling and docking studies for melanogenesis, albinism and increased risk for melanoma.
In a multivariable model that included only the most statistically significant findings from univariable modeling and adjusted for pigmentary phenotype, back nevi, and baseline features, we found TERT/CLPTM1L rs401681 (P = 0.004), TYRP1 rs2733832 (P = 0.006), MTAP rs1335510 (P = 0.0005), TYRrs10830253 (P = 0.003), and MX2 rs45430 (P = 0.008) to be significantly associated with multiple primary melanoma, while NCOA6 rs4911442 approached significance (P = 0.06).
In 53 nevi and 116 primary malignant melanomas, 81% and 52%, respectively, are DCT+/Tyr+, showing that DCT is a stable antigen, retained by most tumors and partially expressed in Tyr-negative cell populations.
Consequently, MTX sensitizes melanomas to a tyrosinase-processed antifolate prodrug 3-O-(3,4,5-trimethoxybenzoyl)-(-)-epicatechin (TMECG), that inhibits the essential enzyme DHFR with high affinity.
Few high penetrance genes are known in Malignant Melanoma (MM), however, the involvement of low-penetrance genes such as MC1R, OCA2, ASIP, SLC45A2 and TYR has been observed.
Critically, such metastatic behavior is transplantable, as intradermal inoculation of melanoma cells from TyrRas-DMBA mice into non-transgenic mice led to the growth of melanoma and, again, metastasis to skin-draining lymph nodes.
Adjustment for all clinical potential confounders showed that melanoma risks attributable to MC1R and SLC45A2 variants strongly persisted (OR: 2.01 95% CI: 1.49-2.72 and OR: 0.50, 95% CI: 0.31-0.80, respectively), while the association of TYRp.Arg402Gln was no longer significant.
The enhancement of tyrosinase gene expression and melanin production by loading the plasmid in elastic cationic niosomes was investigated in tyrosinase gene knocked out human melanoma (M5) cells and in tyrosine-producing mouse melanoma (B(16) F(10) ) cells.
Metastatic HLA-A2.1(+) melanoma patients were vaccinated intravenously (on average 25 × 10(6) DC) and intradermally (on average 11 × 10(6) DC) with mature DC loaded with keyhole limpet hemocyanin (KLH) together with tyrosinase peptide and either wild-type (15 patients) or modified (12 patients) gp100 peptides.
Safety and efficacy of a xenogeneic DNA vaccine encoding for human tyrosinase as adjunctive treatment for oral malignant melanoma in dogs following surgical excision of the primary tumor.
Here we present the first nested polymerase chain reaction process carried out by a microfabricated, hybrid plastic-glass microfluidic chip on the tyrosinase gene, a predictive marker for melanoma diagnosis.
The resulting tyrosinase promoter-regulated and FCU1-encoding adenovirus combined effective oncolysis with targeted prodrug activation therapy of melanoma.
We genotyped a frequent TYR variant (p.R402Q) in 1273 patients {1047 cutaneous melanoma (CM) and 226 basal cell carcinoma (BCC)} and 925 controls, and the full coding region of TYR was sequenced in 287 patients suspected of genetic predisposition to SK (familial and/or multiple SK and/or onset before 40 years) and 187 controls.
Analysis of MITF as an additional marker to tyrosinase allowed for detection of circulating melanoma cells in a larger number of melanoma patients in comparison to tyrosinase analysis alone (48 vs. 20 positive).
The standard curve of the qRT-PCR method used melanoma cell line SK-MEL-28, added to the blood of normal donors and it was calibrated on a synthetic RNA standard (1 SK-MEL-28 cell corresponding to 18 tyrosinase mRNA copies) to improve the procedural standardization to facilitate the comparison of data collected at different laboratories.