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Cancer Immunol Res ; 5(8): 618-629, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28630054


Cytotoxic T lymphocyte (CTL)-based immunotherapies have had remarkable success at generating objective clinical responses in patients with advanced metastatic melanoma. Although the melanocyte differentiation antigens (MDA) MART-1, PMEL, and tyrosinase were among the first melanoma tumor-associated antigens identified and targeted with immunotherapy, expression within normal melanocytes of the eye and inner ear can elicit serious autoimmune side effects, thus limiting their clinical potential as CTL targets. Using a tandem mass spectrometry (MS) approach to analyze the immunopeptidomes of 55 melanoma patient-derived cell lines, we identified a number of shared HLA class I-bound peptides derived from the melanocyte-specific transporter protein SLC45A2. Antigen-specific CTLs generated against HLA-A*0201- and HLA-A*2402-restricted SLC45A2 peptides effectively killed a majority of HLA-matched cutaneous, uveal, and mucosal melanoma cell lines tested (18/25). CTLs specific for SLC45A2 showed significantly reduced recognition of HLA-matched primary melanocytes that were, conversely, robustly killed by MART1- and PMEL-specific T cells. Transcriptome analysis revealed that SLC45A2 mRNA expression in normal melanocytes was less than 2% that of other MDAs, therefore providing a more favorable melanoma-to-melanocyte expression ratio. Expression of SLC45A2 and CTL sensitivity could be further upregulated in BRAF(V600E)-mutant melanoma cells upon treatment with BRAF or MEK inhibitors, similarly to other MDAs. Taken together, our study demonstrates the feasibility of using tandem MS as a means of discovering shared immunogenic tumor-associated epitopes and identifies SLC45A2 as a promising immunotherapeutic target for melanoma with high tumor selectivity and reduced potential for autoimmune toxicity. Cancer Immunol Res; 5(8); 618-29. ©2017 AACR.

Antígenos de Neoplasias/imunologia , Imunoterapia , Melanoma/terapia , Proteínas de Membrana Transportadoras/imunologia , Proteínas Proto-Oncogênicas B-raf/genética , Linfócitos T Citotóxicos/imunologia , Apresentação do Antígeno/genética , Apresentação do Antígeno/imunologia , Antígenos de Neoplasias/genética , Citotoxicidade Imunológica , Epitopos/imunologia , Antígeno HLA-A2/imunologia , Antígeno HLA-A24/imunologia , Humanos , Antígeno MART-1/imunologia , Melanócitos/imunologia , Melanoma/imunologia , Melanoma/patologia , Proteínas de Membrana Transportadoras/genética , Peptídeos/genética , Peptídeos/imunologia , Proteínas Proto-Oncogênicas B-raf/imunologia , Espectrometria de Massas em Tandem , Transcriptoma/genética , Antígeno gp100 de Melanoma/imunologia
Angle Orthod ; 78(2): 234-40, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18251617


OBJECTIVE: To determine the variation in the insertion torque of orthodontic miniscrews according to the screw length, diameter, and shape. MATERIALS AND METHODS: The maximum insertion torque (MIT) was measured using a torque tester at a constant speed of 3 rotations per minute. Cylindrical and taper type of miniscrews (Biomaterials Korea Inc, Seoul, Korea) with different lengths, diameters, and pitches were tested. RESULTS: The results showed that the insertion torque significantly increased with increasing screw length (P < .01). In particular, there was a significant increase in torque with increasing screw length and diameter (P < .01). An analysis of the serial insertion torque of miniscrews revealed the cylindrical type screw to have much higher insertion torque at the incomplete screw thread, while the taper type screw showed a much higher insertion torque at the final inclination part of the screw thread. The insertion torque was affected by the outer diameter, length, and shape in that order. CONCLUSIONS: An increase in screw diameter can efficiently reinforce the initial stability of the miniscrew, but the proximity of the root at the implanted site should be considered.

Parafusos Ósseos , Implantação Dentária Endo-Óssea , Procedimentos de Ancoragem Ortodôntica/instrumentação , Desenho de Aparelho Ortodôntico , Análise do Estresse Dentário , Miniaturização , Análise de Regressão , Torque