RESUMEN
Oral epithelial dysplasia (OED) is a premalignant lesion of the oral mucosa. Considering the poor 5-year survival rate of oral cancer, further investigation is needed in order to determine the pathogenesis of OED. In the present study, serial analysis of gene expression (SAGE) data from patients with OED were compared to normal controls to identify differentially expressed genes (DEGs). SAGE data were obtained from the Gene Expression Omnibus, and included samples from patients with mild, moderate, or severe dysplasia. The DEGs were identified using the edgeR software package and functional-enrichment analysis was performed with the DAVID (https://david.ncifcrf.gov/) software program. The co-expression network was constructed using the CoExpress software and target genes of long non-coding RNAs (lncRNAs) were predicted according to the proximity between the lncRNAs and mRNAs in the genome. A total of 517 DEGs were identified, including 409 mRNAs and 108 lncRNAs. Functional-enrichment analysis showed that mRNAs and lncRNAs involved in epithelial cell differentiation, epithelium development, and epidermal cell differentiation were significantly enriched in the DEGs. Thirty-eight potential regulatory relationships were unveiled between lncRNAs and mRNAs, and two subnetworks were discovered by analyzing the topological properties of the co-expression network. In conclusion, we have identified key mRNAs and lncRNAs in OED, and these findings may aid in understanding the pathogenesis of OED and advance potential future treatments.
Asunto(s)
Regulación Neoplásica de la Expresión Génica , Mucosa Bucal/metabolismo , Neoplasias de la Boca/genética , Lesiones Precancerosas/genética , ARN Largo no Codificante/genética , ARN Mensajero/genética , Diferenciación Celular , Bases de Datos Genéticas , Células Epiteliales/metabolismo , Células Epiteliales/patología , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Anotación de Secuencia Molecular , Mucosa Bucal/patología , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/patología , ARN Largo no Codificante/metabolismo , ARN Mensajero/metabolismo , Índice de Severidad de la Enfermedad , Programas InformáticosRESUMEN
Antibody-mediated rejection (AMR) is an important factor affecting survival after renal transplantation. A highly selective proteasome inhibitor, bortezomib, clears activated plasma cells from the body and has important therapeutic effect on AMR. We investigated the effects of bortezomib on AMR in a patient after a second renal transplant. Biopsy confirmed the diagnosis of mixed cellular rejection and AMR. Bortezomib was administered on day 1 (1.3 mg/m(2)), day 4 (1.0 mg/m(2)), and day 8 (1.0 mg/m(2)). On the same days, 250 mg methylprednisolone was administered once, and cyclosporine dose (5 mg·kg(-1)·day(-1)) was reduced by 50%. Oral mycophenolate mofetil and steroid were withdrawn on day 1 of bortezomib treatment. Intermittent double-filtration plasmapheresis was also performed. We monitored parameters, including T lymphocyte subsets, CD139 and CD19 expression, panel reactive antibody (PRA), and serum creatinine concentration. At follow-up 6 months after bortezomib treatment, we observed: 1) serum creatinine stabilized at 130 µM from a peak level of 337 µM; 2) PRA decreased from a maximum of 66.7 to 0%; 3) blood plasma cell percentage rebounded after significantly decreasing following the first dose of bortezomib; 4) in renal allograft biopsy, immunohistochemical staining for C4d shifted from strongly positive to negative, and cellular rejection shifted from type IIA to borderline; and 5) adverse effects such as platelet suppression, hypotension, and grade 3 peripheral neuropathy emerged. Bortezomib effectively treated antibody-mediated renal transplantation rejection in this case study, but clinical trials with large sample sizes are still needed to explore clinical safety and tolerability.
Asunto(s)
Anticuerpos/efectos adversos , Bortezomib/efectos adversos , Rechazo de Injerto/tratamiento farmacológico , Trasplante de Riñón/efectos adversos , Anticuerpos/inmunología , Bortezomib/administración & dosificación , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/patología , Humanos , Riñón/efectos de los fármacos , Riñón/inmunología , Riñón/patología , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/análogos & derivados , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/patología , Trasplante Homólogo/efectos adversosRESUMEN
Although there is evidence suggesting genetic susceptibility for keloids, studies investigating the association between Arg72Pro polymorphism in the P53 gene and tendency to form keloids have given variable results. We made a meta-analysis of the effects of P53 Arg72Pro polymorphism on keloid risk in the Chinese population by conducting searches of the published literature in Pubmed, Embase, CBMdisc, and CNKI databases up to June 2011. Six studies were included in the meta-analysis, with a total of 359 keloid cases and 493 healthy controls. Meta-analysis results, respectively in the PCR-reverse dot blot and PCR-RFLP subgroups, showed significant associations between P53 Arg72Pro polymorphism and susceptibility to keloid in the comparisons of Pro allele vs Arg allele (odds ratio (OR) = 2.29, 95% confidence interval (CI) = 1.45-3.60; OR = 0.74, 95%CI = 0.56-0.98); Pro/Pro vs Pro/Arg + Arg/Arg (OR = 2.91, 95%CI = 1.88-4.53; OR = 0.54, 95%CI = 0.32-0.92); Pro/Pro vs Arg/Arg (OR = 2.79, 95%CI = 1.54-5.06; OR = 0.51, 95%CI = 0.28-0.92); Pro/Pro vs Pro/Arg (OR = 2.85, 95%CI = 1.75-4.63; OR = 0.57, 95%CI = 0.32-0.99). We conclude that the Pro allele of P53 Arg72Pro polymorphism is a risk factor for keloids in the Chinese population.