RESUMEN
The NF1 gene is related to neurofibromatosis type 1 (NF1), which is an autosomal dominant disorder associated with multisystem involvement and epilepsy susceptibility. A human induced pluripotent stem cell (iPSC) line was derived from a pediatric patient with NF1 and epilepsy, harboring a heterozygous NF1 gene mutation. The iPSC line exhibits high levels of pluripotency markers, maintains the NF1 gene mutation, and demonstrates the capacity to undergo differentiation potential in vitro into three germ layers. The iPSC line will serve as a valuable resource for investigating the underlying mechanisms and conducting drug screening related to NF1 and NF1-associated epilepsy.
Asunto(s)
Epilepsia , Heterocigoto , Células Madre Pluripotentes Inducidas , Mutación , Neurofibromatosis 1 , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/patología , Neurofibromatosis 1/genética , Neurofibromatosis 1/patología , Epilepsia/genética , Epilepsia/patología , Neurofibromina 1/genética , Línea Celular , Diferenciación Celular , Masculino , Genes de Neurofibromatosis 1RESUMEN
To address the relationship of altered expression of double-strand break repair proteins Ku70 and p53 in clinical colorectal cancer (CRC), we examined the expression pattern of Ku70 and p53 by using fluorescent immunohistochemistry and real-time PCR assays in CRC and pericancerous samples from 152 Chinese patients. The results showed that down-expression pattern of both Ku70 and p53 coexisted in the CRC samples with significant correlating rate (R (2) = 0.9103; P < 0.001), and the down-expression of Ku70 and p53 was significantly associated with the advanced tumor node metastasis stage (Ku70: HR 3.453 in recurrence and 4.182 in survival, P < 0.001; P53: HR 3.114 in recurrence and 4.113 in survival, P < 0.001). The down-regulated Ku70 and p53 were associated with poor disease-free survival. Loss of Ku70 and p53 expression might serve as a biomarker of poor prognosis in CRC patients.
Asunto(s)
Antígenos Nucleares/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/metabolismo , Proteínas de Unión al ADN/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Antígenos Nucleares/genética , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Proteínas de Unión al ADN/genética , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Autoantígeno Ku , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Proteína p53 Supresora de Tumor/genéticaRESUMEN
BACKGROUND: Double-strand DNA breaks (DSBs) are a key factor in carcinogenesis. The necessary repair of DSBs is pivotal in maintaining normal cell division. To address the relationship between altered expression of DSB repair of proteins Ku70 and ataxia-telangiectasia mutated (ATM) in colorectal cancer (CRC), we examined the expression levels and patterns of Ku70 and ATM in CRC samples. METHODS: Expression and coexpression of Ku70 and ATM were investigated by using real-time quantitative polymerase chain reaction assays and confirmed further with fluorescent immunohistochemistry in CRC and pericancerous samples from 112 Chinese patients. RESULTS: Downexpression patterns for both Ku70 and ATM were found in the CRC samples and were significantly associated with advanced tumor node metastasis stage and decreased 5-year overall survival rate. CONCLUSION: Downregulated Ku70 and ATM were associated with poor disease-free survival. Loss of Ku70 and ATM expression might act as a biomarker to predict poor prognosis in patients with CRC.
RESUMEN
OBJECTIVE: The current study is to evaluate the effect of thymidylate synthase (TYMS) on lymph node metastasis (LNM) in Chinese colorectal cancer (CRC) patients, and develop potential LNM-associated biomarkers for CRC. DESIGN AND METHODS: Differences in TYMS gene expression between primary CRC with LNM (LNM CRC) and without LNM (non-LNM CRC) were assessed using quantitative real-time PCR analysis in 100 Chinese colorectal cancer patients. The relationship between clinicopathological parameters and prognosis of candidate biomarkers was also examined in the experiment. RESULTS: TYMS was significantly upregulated in LNM CRC compared with non-LNM CRC, which was confirmed by real-time quantitative polymerase chain reaction. Overexpression of TYMS was significantly associated with LNM (P<0.001), advanced TNM stage (P<0.001), increased 5-year recurrence rate (P<0.001) and decreased 5-year overall survival rate (P<0.001). Univariate and multivariate analyses indicated that TYMS expression was an independent prognostic factor for recurrence and survival of CRC patients (P<0.05). CONCLUSIONS: TYMS effect on lymph node metastasis in CRC might serve as a potential biomarker for LNM and a prognostic factor in CRC. Over-expression of TYMS is a predicting factor to the poor outcome in clinical colorectal cancer patients.