RESUMO
BACKGROUND: Little is known about epigenetic silencing of genes by promoter hypermethylation in renal cell carcinoma (RCC). The aim of this study was to identify prognostic methylation markers in surgically treated clear cell RCC (ccRCC). METHODS: Methylation patterns were assayed using the Infinium HumanMethylation450 BeadChip array on pairs of ccRCC and normal tissue from 12 patients. Using quantitative PSQ analysis, tumor-specific hypermethylated genes were validated in 25 independent cohorts and their clinical relevance was also verified in 152 independent cohorts. RESULTS: Using genome-wide methylation array, Zinc finger protein 278 (ZNF278), Family with sequence similarity 155 member A (FAM155A) and Dipeptidyl peptidase 6 (DPP6) were selected for tumor-specific hypermethylated genes in primary ccRCC. The promoter methylation of these genes occurred more frequently in ccRCC than normal kidney in independent validation cohort. The hypermethylation of three genes were associated with advanced tumor stage and high grade tumor in ccRCC. During median follow-up of 39.2 (interquartile range, 15.4-79.1) months, 22 (14.5%) patients experienced distant metastasis. Multivariate analysis identified the methylation status of these three genes, either alone, or in a combined risk score as an independent predictor of distant metastasis. CONCLUSION: The promoter methylation of ZNF278, FAM155A and DPP6 genes are associated with aggressive tumor phenotype and early development of distant metastasis in patients with surgically treated ccRCC. These potential methylation markers, either alone, or in combination, could provide novel targets for development of individualized therapeutic and prevention regimens.
Assuntos
Carcinoma de Células Renais/patologia , Metilação de DNA , Neoplasias Renais/patologia , Idoso , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/cirurgia , Análise por Conglomerados , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Fatores de Transcrição Kruppel-Like/genética , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Proteínas do Tecido Nervoso/genética , Canais de Potássio/genética , Intervalo Livre de Progressão , Proteínas Repressoras/genética , Fatores de RiscoRESUMO
PURPOSE: To report a case of recurrent herpes simplex keratitis after verteporfin photodynamic therapy for corneal neovascularization. METHODS: A 69-year-old man who had lipid keratopathy with corneal neovascularization secondary to herpes simplex keratitis in the right eye and who was treated with topical steroid received photodynamic therapy with verteporfin. Six neovascular areas in the cornea were treated consecutively to occlude new vessels and reduce the risk of allograft rejection after subsequent keratoplasty. RESULTS: Three days after verteporfin photodynamic therapy, there was evidence of vascular occlusion. However, a herpetic epithelial ulcer was detected in the cornea. Ten days after treatment, the lesion progressed to a geographic ulcer. After topical and systemic acyclovir treatment, the lesion healed. Five months after treatment, penetrating keratoplasty and postoperative antiviral prophylaxis were performed. During a follow-up period of 12 months, the graft remained clear with visual acuity of 20/40. CONCLUSION: Herpes simplex keratitis can recur after verteporfin photodynamic therapy for corneal neovascularization.
Assuntos
Neovascularização da Córnea/tratamento farmacológico , Ceratite Herpética/etiologia , Fotoquimioterapia/efeitos adversos , Fármacos Fotossensibilizantes/efeitos adversos , Porfirinas/efeitos adversos , Ativação Viral/efeitos dos fármacos , Aciclovir/uso terapêutico , Idoso , Antivirais/uso terapêutico , Humanos , Ceratite Herpética/diagnóstico , Ceratite Herpética/tratamento farmacológico , Masculino , Recidiva , Verteporfina , Acuidade VisualRESUMO
PURPOSE: To investigate the expression of CXCL9, -10, -11, and CXCR3 in the tear film and ocular surface of patients with dry eye syndrome. METHODS: Thirty-three patients with dry eye (16 with and 17 without Sjögren's syndrome) and 15 control subjects were recruited. The concentrations of CXCL9, -10, and -11 in tears were measured with enzyme-linked immunosorbent assays. The correlation between chemokine levels and tear film and ocular surface parameters was analyzed. The expression of CXCL9, -10, -11, and CXCR3 in the conjunctiva was evaluated by using immunohistochemistry. Flow cytometry was performed to count CXCR3(+) cells and CXCR3(+)CD4(+) cells in the conjunctiva. RESULTS: The concentrations of CXCL9, -10, and -11 were 1,148 +/- 1,088, 24,338 +/- 8,706, and 853 +/- 334 pg/mL, in the patients with dry eye, and 272 +/- 269 (P = 0.01), 18,149 +/- 5,266 (P = 0.02), and 486 +/- 175 (P < 0.01) pg/mL in the control subjects, respectively. The concentrations significantly increased in tears of the patients with Sjögren's syndrome compared with those of the patients with non-Sjögren's dry eye (P < 0.05). CXCL10 levels correlated significantly with basal tear secretion, and CXCL11 levels correlated significantly with basal tear secretion, tear clearance rate, keratoepitheliopathy score, and goblet cell density (P < 0.05). Staining for CXCL9, -10, -11, and CXCR3 increased in patients with dry eye, especially in the patients with Sjögren's syndrome. Flow cytometry demonstrated an increased number of CXCR3(+) and CXCR3(+)CD4(+) cells in all the patients with dry eye. CONCLUSIONS: Expression of CXCL9, -10, -11, and CXCR3 increased in the tear film and ocular surface of patients with dry eye syndrome, especially in those with Sjögren's syndrome. CXCL11 levels correlated significantly with various tear film and ocular surface parameters. (ClinicalTrials.gov number, NCT00991679.).
