RESUMEN
Thyroid cancer is the most common type of malignant endocrine tumor diagnosed. Previous studies have indicated that gene therapy is the most promising and effective therapeutic method for thyroid cancer. Therefore, in the present study, Na131I/5-fluorocytosine (5-FC) treatment was combined with cytosine deaminase (CD, encoded by the CDA gene) and sodium iodide symporter (NIS, encoded by the SLC5A5 gene) to act together as a therapeutic tool for thyroid cancer. The present study explored the combined cytotoxic effects of adenovirus-mediated CD and NIS under the control of the progression elevated gene-3 (PEG-3) promoter (Ad-PEG-3-CD-NIS) with Na131I/5-FC against the human thyroid cancer TT cell line in vitro. The PEG-3 fragment was obtained by polymerase chain reaction (PCR) using rat genomic DNA as the template, and then Ad-PEG-3-CDA-SLC5A5 was constructed using XbaI. TT cells were transfected by recombinant adenovirus. The method of reverse transcription-quantitative PCR was performed to test the expression of CD and NIS at the level of transcription. The morphological change was assessed by fluorescence microscopy and investigated by western blot analysis. An MTT assay was used to determine the number of living cells inhibited by single or combination therapies on TT cells. The results indicated that the PEG-3 was successfully cloned, and was also positively regulated in 293 cells. CDA and SLC5A5 genes were highly expressed in TT cells. Na131I combined with 5-FC significantly decreased the human thyroid cancer cells. In conclusion, combination therapy of Ad-PEG3-CDA-SLC5A5 and Na131I/5-FC induces significantly more apoptotic characteristics than either single treatment with Ad-PEG-3-CDA-SLC5A5 or Na131I/5-FC, and low doses of Ad-PEG-3-CDA-SLC5A5 enhanced the cytotoxic effects.
RESUMEN
Multiple sclerosis (MS) is an autoimmune/inflammatory neurodegenerative disease which mainly affects the central nervous system in young adults. Fc-receptor-like-3 (FCRL3) gene, which involved in immune cell regulation, has drawn lots of attentions. This study aims to investigate the association between common polymorphisms of FCRL3 gene and MS risk in a Chinese Han population. Nine single nucleotide polymorphisms (SNPs) were genotyped in 120 patients and 240 healthy controls through PCR assay. t test and chi-square test was conducted to find a possible association between FCRL3 genetic mutations and risk of MS. This analysis results performed that four SNPs, rs7528684 (FCRL3_3), rs945635 (FCRL3_5), rs3761959 (FCRL3_6), and rs2282284 (FCRL3_8), were significantly associated with the risk of MS. Further haplotype analysis showed two haplotypes of FCRL3_3, 5, 6, 8, CCAG and CGAG, presented the significant associations with the susceptibility to MS. Four SNPs in FCRL3 gene could possibly associate with the susceptibility of MS in a Chinese Han population. Moreover, the haplotype analysis confirmed that the linkage disequilibrium exists in polymorphisms in FCRL3. Based on the supporting evidence, we deduced that FCRL3_3C, FCRL3_5C, FCRL3_6A, and FCRL3_8G caused increased risk of MS. Nevertheless, large cohort studies are required in the future to validate the autoimmune function.
Asunto(s)
Predisposición Genética a la Enfermedad , Esclerosis Múltiple/genética , Polimorfismo de Nucleótido Simple/genética , Receptores Inmunológicos/genética , Adulto , Alelos , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Haplotipos/genética , Humanos , Masculino , Modelos BiológicosRESUMEN
Cardiac hypertrophy is a primary pathological change associated with cardiovascular diseases. Dysregulated microRNAs are frequent in cardiovascular diseases and contribute to cardiac hypertrophy by regulating a series of targeted genes. In this study, a rat model of cardiac hypertrophy was created by transverse abdominal aortic constriction, and cardiomyocyte hypertrophy in cultured neonatal rat cardiomyocytes was induced using angiotensin II (AngII) to investigate the role of miR-101 in myocardial hypertrophy. We demonstrated that miR-101 was downregulated in both the transverse abdominal aortic constriction rat model and hypertrophic cardiac myocytes. The overexpression of miR-101 in neonatal rat cardiomyocytes, which was accompanied by a reduced Rab1a level, inhibits 3 cardinal features of cardiomyocyte hypertrophy: fetal gene expression, protein synthesis, and cell enlargement. Conversely, the downregulation of miR-101 reverses these effects. Furthermore, the luciferase reporter system demonstrated that Rab1a is a target gene of miR-101, and the ectopic expression of Rab1a can reverse the cardiomyocyte hypertrophy inhibitory activity of miR-101. Taken together, our findings identify miR-101 as an important regulator in cardiac hypertrophy and implicate the potential application of miR-101 in the therapy of cardiac hypertrophy.
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Cardiomegalia , MicroARNs/genética , Miocitos Cardíacos/metabolismo , Proteínas de Unión al GTP rab1/metabolismo , Animales , Cardiomegalia/genética , Cardiomegalia/metabolismo , Células Cultivadas , Modelos Animales de Enfermedad , Regulación hacia Abajo , Expresión Génica Ectópica , Proteínas de Unión al GTP Monoméricas/metabolismo , Ratas , Regulación hacia ArribaRESUMEN
The aim of this study was to detect stress-induced phosphoprotein 1 (STIP1) expression in papillary thyroid carcinoma (PTC) and to analyze its association with prognosis of PTC patients. Immunohistochemistry was performed to detect the expression of STIP1 in 113 PTC tissues and paired adjacent noncancerous tissues. The χ2 test was used to analyze the relationship between STIP1 expression and clinicopathological characteristics. Survival curves were plotted by the Kaplan-Meier method and compared using the log-rank test. Survival data was evaluated using univariate and multivariate Cox regression analysis. We identified abnormally elevated expression of STIP1 protein in PTC tissues compared to paired adjacent noncancerous tissues. Clinicopathological analysis showed that STIP1 expression was significantly correlated with tumor size (P = 0.017), lymph node metastasis (P = 0.007), and TNM stage (P = 0.026). Patients with higher STIP1 expression had shorter overall survival time, whereas those with lower STIP1 expression had longer survival time. Multivariate analysis suggested that STIP1 expression might be an independent prognostic indicator (P < 0.05) for the survival of patients with PTC. In conclusion, our findings provide evidences that positive expression of STIP1 in PTC may be important in the acquisition of an aggressive phenotype, and it is an independent biomarker for poor prognosis of patients with PTC.
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Biomarcadores de Tumor/análisis , Carcinoma/metabolismo , Carcinoma/mortalidad , Carcinoma/patología , Proteínas de Choque Térmico/biosíntesis , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología , Adulto , Anciano , Carcinoma Papilar , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Cáncer Papilar TiroideoRESUMEN
The aim of this study was to detect FOXC1 expression in human non-small cell lung cancer (NSCLC) and to analyze its association with prognosis of NSCLC patients. Expressional levels of FOXC1 mRNA and protein in 30 cases of NSCLC and corresponding non-tumor tissue samples were examined by quantitative real-time PCR and Western blotting. Immunohistochemistry was performed to detect the expression of FOXC1 in 125 NSCLC tissues. We found that the expression levels of FOXC1 mRNA and protein in NSCLC tissues were significantly higher than those in corresponding non-tumor tissues. High-level FOXC1 expression was correlated with poor tumor differentiation, tumor-node-metastasis stage, and lymph node metastasis. Patients with high expression levels of FOXC1 showed lower overall survival rate than those with low expression levels. Multivariate analysis showed that high FOXC1 protein expression was an independent prognostic factor for NSCLC patients. Our study suggests that over-expression of FOXC1 may play an important role in the progression of NSCLC, and FOXC1 expression may offer a valuable marker for predicting the outcome of patients with NSCLC.
Asunto(s)
Adenocarcinoma/mortalidad , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Células Escamosas/mortalidad , Factores de Transcripción Forkhead/metabolismo , Neoplasias Pulmonares/mortalidad , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Western Blotting , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Femenino , Estudios de Seguimiento , Factores de Transcripción Forkhead/genética , Humanos , Técnicas para Inmunoenzimas , Pulmón/metabolismo , Pulmón/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , 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 SupervivenciaRESUMEN
OBJECTIVE: To study the clinical value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the diagnosis and staging of lung cancer. METHODS: Ninety-four patients with lung nodular changes were examined by CT, 18F-FDG PET and pathology, cytology. 18F-FDG PET images were analyzed by semi-quantitative standard uptake value (SUV) only and (or) SUV plus visual observation. Focuses with a SUV > 2.5 were judged as malignant changes, while SUV < or = 2.5 was judged as benign. SUV plus visual analysis, based on the focal SUV, the nodular size and shape, and clinical data, was carried out by two nuclear doctors. CT imaging was interpreted by two radiological doctors. The sensitivity, specificity, accuracy, positive predictive and negative predictive values of 18F-FDG PET and CT in the diagnosis, and in the evaluation of lymphatic metastasis and remote metastasis of lung lesions were calculated. The diagnostic efficiency of the two methods (SUV or visual plus SUV method) was compared. RESULTS: (1) 58 cases were confirmed to be malignant by surgery or pathological examination, while 36 cases were proved benign by pathology or empirical therapy. (2) The sensitivity, specificity, accuracy, positive and negative predictive values were 69%, 65%, 68%, 82% and 49% respectively for CT; and 91%, 89%, 90%, 93% and 87% respectively for SUV analysis; and 95%, 94%, 95%, 97% and 92% respectively for visual plus SUV methods. (3) Among 34 patients with mediastinal lymph node involvement confirmed by pathology, 18F-FDG PET detected 30 cases, while CT detected only 18 cases (P < 0.01). (4) 18F-FDG PET revealed 19 cases with distant metastases, while CT only discovered 8 cases with distant metastases. As a result, the therapy was modified by PET examination in 14 patients. CONCLUSION: 18F-FDG PET imaging is of important clinical value in the diagnosis of lung lesions and the staging of malignancy.