RESUMEN
This study aimed to investigate the mechanism underlying the inhibitory effect of tumor suppressor gene miR-186 and zinc finger protein 545 (ZNF545) on the proliferation of multiple myeloma (MM) cells. CD138 magnetic beads were used to isolate different types of myeloma cell lines (KM3, U266, RPMI-8226, and H929), which were then infected by lentivirus carrying the miR-186 gene. Using uninfected myeloma cells as the control, MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide] assay was performed to calculate the rate of cell proliferation at different time points. In addition, the correlation between the expression of Jagged 1 and miR-186 was analyzed by real-time Polymerase Chain Reaction (PCR). Furthermore, the effect of 5-Aza-2-deoxycytidine and acetylase inhibitor Trichomycin A (TSA) on the expression of ZNF545 and proliferation/apoptosis of MM cells was investigated using Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western blotting (WB), MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] cell proliferation assay, and Annexin V-FITC/PI staining. Compared with the control group, the proliferation of miR-186-overexpressing U266 and RPMI-8226 cells was significantly decreased. In cell cloning experiments, miR-186 decreased the number of U266 and RPMI-8226 clones while reducing the protein expression of Jagged 1. The expression level of ZNF545 in myeloma patients was also reduced to some extent. ZNF545 protein also promoted the apoptosis of myeloma cells. By inhibiting the proliferation of myeloma cells, miR-186 gene and ZNF protein may be used as tumor suppressors in the treatment of myeloma.
Asunto(s)
Proliferación Celular , MicroARNs/metabolismo , Mieloma Múltiple/patología , Proteínas Nucleares/metabolismo , Apoptosis , Línea Celular Tumoral , HumanosRESUMEN
Background Non-invasive prenatal screening (NIPS) using cell-free foetal DNA (cfDNA) has been widely used for identifying common foetal aneuploidies (e.g. trisomy 21 (T21), trisomy (T18) and trisomy 13 (T13)) in clinical practice. The sensitivity and specificity of NIPS exceeds 99%, but the positive prediction value (PPV) is approximately 70% (combined T21, T18 and T13). Thus, some 30% of pregnant women who have positive NIPS results are eventually identified as normal by amniocentesis. These women therefore must undertake needless invasive tests and risk miscarrying healthy babies because of false positive NIPS results. Methods In order to achieve higher accuracy, we amended the standard NIPS (s-NIPS) protocol with an additional cfDNA size selecting step in agarose-electrophoresis. The advantage of the new method (named e-NIPS) was validated by comparing the results of e-NIPS and s-NIPS using 114 retrospective cases selected from 15,930 cases. Results Our results showed that the foetal cfDNA fraction can be enriched significantly by a size selection step. With this modification, all 98 negative cases and 9 of 11 false positive cases of s-NIPS were correctly identified by e-NIPS, resulting in an increased PPV from 71% to 77%. Additionally, a simulation test showed that e-NIPS is more reliable than s-NIPS, especially when the foetal cfDNA concentration and sequencing coverage are low. Conclusion cfDNA size selection is an important step in improving the accuracy of non-invasive prenatal screening for chromosomal abnormalities.
Asunto(s)
Ácidos Nucleicos Libres de Células/genética , Síndrome de Down/genética , Diagnóstico Prenatal/métodos , Trisomía/genética , Adulto , Aneuploidia , Ácidos Nucleicos Libres de Células/aislamiento & purificación , Síndrome de Down/sangre , Síndrome de Down/patología , Femenino , Desarrollo Fetal/genética , Feto/patología , Humanos , Embarazo , Estudios RetrospectivosRESUMEN
Three cases of children, aged 7, 12 and 13 years, respectively, with bronchial mucoepidermoid carcinoma are presented. All patients were primarily misdiagnosed as pneumonitis following common symptoms of prolonged fever, cough, expectoration, and indirect signs of bronchial obstruction by chest roentgenogram, before the tumours in the main bronchi were revealed by chest computed tomography and bronchoscopy. After undergoing lobectomy and systematic lymph node dissection, all three patients recovered uneventfully. Histologically, all the cases were low-grade mucoepidermoid carcinoma; one case additionally had mediastinal lymph node metastasis. The patients have remained in good health during a follow-up of between 1.5 and 6 years. Despite its extremely rare occurrence in childhood, the possibility of bronchial mucoepidermoid carcinoma should be kept in mind when encountering a child presenting with symptoms of recurrent pneumonia.
Asunto(s)
Neoplasias de los Bronquios , Carcinoma Mucoepidermoide , Adolescente , Biopsia , Neoplasias de los Bronquios/diagnóstico por imagen , Neoplasias de los Bronquios/patología , Neoplasias de los Bronquios/cirugía , Carcinoma Mucoepidermoide/diagnóstico por imagen , Carcinoma Mucoepidermoide/patología , Carcinoma Mucoepidermoide/cirugía , Niño , Errores Diagnósticos , Femenino , Humanos , Escisión del Ganglio Linfático , Masculino , Neumonectomía , Neumonía/diagnóstico , Valor Predictivo de las Pruebas , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Selenium (Se) is an essential trace element for animals. Selenocysteine (Sec), the 21st aminoacid, is a component of selenoproteins and has been founded in the active center of selenoenzymes. The functions of Se within the body have been primarily shown in the forms of selenoproteins, especially selenoenzymes. Incorporation of selenocysteine occurs on the basis of genetic expression and Se is the only trace element under direct genetic control. Recently, findings have shown that Se and selenocompounds conducted many other potential functions such as protection against inflammatory factors, inhibition of protein kinase C (PKC), stimulation of MAP kinase (mitogen activated protein kinase/myelin basic protein kinase) and S6 kinase (ribosomal S6 protein kinase), regulation of the immune system and interaction with other elements and vitamins etc, suggesting that the roles of Se in human health may be more diverse than previously suspected.
Asunto(s)
Selenio/fisiología , Selenocisteína/fisiología , Humanos , Proteínas/fisiología , Selenoproteínas , Reductasa de Tiorredoxina-Disulfuro/fisiologíaRESUMEN
AIM: To explore the value of morphological classification in predicting malignant transformation in multiple exostoses (ME). PATIENTS AND METHODS: The imaging data of 116 patients (totally 190 tumors) with ME were retrospectively analyzed. All the tumors were pathology confirmed after surgical resection, including 175 exostoses from 101 patients, and 15 exostotic chondrosarcomas in 15 cases. Based on the ratio of diameter between tumor tip and tumor base (R1), tumors were classified into two types: cauliflower-like tumor (R1 ≥ 1.0) and non-cauliflower-like tumor (R1 < 1.0). In addition, non-cauliflower-like tumors were further classified into two subtypes according to the ratio of tumor height to tumor base diameter: sessile type (R2 < 1.0) and pedunculated type (R2 ≥ 1.0). The relationship between tumor shape and malignant transformation was studied. RESULTS: Of all the 175 exostoses from 101 patients, 27 were cauliflower-like tumors and 148 were non-cauliflower-like tumors. Of all the 15 exostotic chondrosarcomas in 15 cases, most tumors were cauliflower-like (c2 = 38.0075, p < 0.05). Cauliflower-like tumor for the prediction of exostotic chondrosarcoma, the sensibility, specificity, positive predictive value, negative predictive value were 86.7%, 84.6%, 32.5%, 98.7%, respectively. CONCLUSIONS: Tumor malignant transformation was more common in cauliflower-like tumors than in non-cauliflower-like tumors. The morphological classification and preventive resection of cauliflower-like tumors maybe helpful in preventing the malignant transformation of ME.