RESUMO
PURPOSE: Increasing evidences suggest dysfunctions of microRNAs (miRNAs) are playing important part in tumors. Therefore, the role of miR-802 in osteosarcoma (OS) was exploited. The object was to evaluate the effect of miR-802 and verify its influence on p27 Kip1 (p27) in OS. METHODS: RT-qPCR experiment was used to detect miR-802 and p27 expression in OS tissues and cells. We explored the function of miR-802 through Transwell assays. The phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase pathway and epithelial-mesenchymal transition (EMT) was detected by Western blot assays. Luciferase assay was used to testify the target of miR-802. RESULTS: MiR-802 expression was elevated in OS, which was related to poor clinical outcome in OS patients. MiR-802 overexpression promoted OS migration, invasion and EMT. Further, p27 is a direct target of miR-802. P27 elevation counteracted the promotion effect of OS on EMT, migration and invasion induced by miR-802. In addition, miR-802 overexpression inactivated PI3K/AKT pathway via targeting p27 in OS. CONCLUSION: MiR-802 promoted the progress of EMT, migration and invasion in OS via targeting p27. This newly identified miR-802/p27/PI3K/AKT axis may represent potential targets for OS.
Assuntos
Neoplasias Ósseas/etiologia , Inibidor de Quinase Dependente de Ciclina p27/fisiologia , MicroRNAs/fisiologia , Osteossarcoma/etiologia , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Adolescente , Neoplasias Ósseas/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Osteossarcoma/patologia , Adulto JovemRESUMO
The aim of this research was to explore whether IL-18 can be a serological marker for the diagnosis of systemic-onset juvenile idiopathic arthritis (sJIA). A total of 23 sJIA patients (13 males, median age 8.2), 20 acute lymphoblastic leukemia (ALL) patients, 18 patients with severe infections (SIF), 26 Kawasaki disease (KD) patients, 18 juvenile idiopathic arthritis (JIA) patients, and 25 healthy control patients were selected for this study. Enzyme-linked immunosorbent assays (ELISAs) were used to determine the serum concentrations of the S100A8, S100A9, and IL-6 proteins. The serum IL-18 levels were detected by a cytometric bead array (CBA). The serum IL-6 concentrations in various disease groups were significantly higher than that in the healthy control group. The IL-6 concentrations exhibited no significant difference between disease groups. The S100A8 level in the sJIA group was significantly higher than those of the ALL, JIA, and healthy control groups but showed no significant difference compared to the SIF and KD groups. The S100A9 serum concentration in the sJIA group was significantly higher than those in the ALL and healthy control groups and exhibited no significant difference from the SIF, KD, and JIA groups. The IL-18 level of the sJIA group was significantly higher than that of the other febrile disease groups. The IL-18 serum concentration may be used as a biological serum marker to distinguish sJIA from other febrile diseases.
Assuntos
Artrite Juvenil/diagnóstico , Interleucina-18/sangue , Artrite Juvenil/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , MasculinoRESUMO
The aim of this research was to explore whether IL-18 can be a serological marker for the diagnosis of systemic-onset juvenile idiopathic arthritis (sJIA). A total of 23 sJIA patients (13 males, median age 8.2), 20 acute lymphoblastic leukemia (ALL) patients, 18 patients with severe infections (SIF), 26 Kawasaki disease (KD) patients, 18 juvenile idiopathic arthritis (JIA) patients, and 25 healthy control patients were selected for this study. Enzyme-linked immunosorbent assays (ELISAs) were used to determine the serum concentrations of the S100A8, S100A9, and IL-6 proteins. The serum IL-18 levels were detected by a cytometric bead array (CBA). The serum IL-6 concentrations in various disease groups were significantly higher than that in the healthy control group. The IL-6 concentrations exhibited no significant difference between disease groups. The S100A8 level in the sJIA group was significantly higher than those of the ALL, JIA, and healthy control groups but showed no significant difference compared to the SIF and KD groups. The S100A9 serum concentration in the sJIA group was significantly higher than those in the ALL and healthy control groups and exhibited no significant difference from the SIF, KD, and JIA groups. The IL-18 level of the sJIA group was significantly higher than that of the other febrile disease groups. The IL-18 serum concentration may be used as a biological serum marker to distinguish sJIA from other febrile diseases.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Artrite Juvenil/diagnóstico , Interleucina-18/sangue , Artrite Juvenil/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Diagnóstico Diferencial , Ensaio de Imunoadsorção EnzimáticaRESUMO
The objective of this study was to investigate the effect of sodium acetate on the viability of the human gastric adenocarcinoma (AGS) epithelial cell line. AGS cells were exposed to a range of concentrations of sodium acetate for different periods of time, and the sodium acetate-induced cytotoxic effects, including cell viability, DNA fragmentation, apoptotic gene expression, and caspase activity, were assessed. The changes in these phenotypes were quantified by performing a lactate dehydrogenase cell viability assay, annexin V staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and several caspase activity assays. In vitro studies demonstrated that the cytotoxicity of sodium acetate on the AGS cell line were dose- and time-dependent manners. No differences were found between the negative control and sodium acetate-treated cells stained with annexin V and subjected to the TUNEL assay. However, caspase-3 activity was increased in AGS cells exposed to sodium acetate. Overall, it was concluded that sodium acetate exerted an apoptotic effect in AGS cells via a caspase-dependent apoptotic pathway.
Assuntos
Adenocarcinoma/patologia , Apoptose/efeitos dos fármacos , Células Epiteliais/patologia , Acetato de Sódio/farmacologia , Neoplasias Gástricas/patologia , Adenocarcinoma/enzimologia , Caspases/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/enzimologia , Histonas/metabolismo , Humanos , Neoplasias Gástricas/enzimologiaRESUMO
BACKGROUND: To determine the effects of endostatin on vascular growth factor receptor 2 (VEGFR2) expression in non-small cell lung cancer (NSCLC) cells and the mechanisms underlying its radiosensitizing effect. METHODS: VEGFR2 mRNA levels were determined in different NSCLC cell lines using qRT-PCR. RT-PCR and Western blot assays were used to assess the expression of mRNA and proteins. The radiosensitivity of the cells was determined by colony-formation assays; and cell apoptosis and cell cycle distribution were determined by flow cytometry. RESULTS: VEGFR2 mRNA levels differed among the five NSCLC cell lines (P < 0.01), with the highest expression in Calu-1 cells and lowest in A549 cells. Endostatin significantly inhibited the growth of Calu-1 cells (P < 0.01) (IC20 = 296.5 µg/ml), and the expression of VEGFR2 and HIF-1α (P < 0.05). Phosphorylation of protein kinase B (Akt), extracellular signal-regulated kinases 1/2 (ERK1/2), and p38 were significantly lower in endostatin-treated cells than control (P < 0.05). Endostatin enhanced the radiosensitivity of Calu-1 cells to SER = 1.38 and induced apoptosis (P < 0.01) and G2/M blockage (P < 0.01). However, endostatin had limited effects on A549 cells. Compared with Calu-1 cells, there was not significantly effects on cell radiosensitivity (SER = 1.09). CONCLUSIONS: Endostatin induces apoptosis and enhances radiosensitivity of the VEGFR2 high-expressing cell line Calu-1, but it has a limited effect on the VEGFR2 low-expressing cell line A549.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Endostatinas/farmacologia , Neoplasias Pulmonares/genética , Radiossensibilizantes/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Raios gama , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/patologia , Tolerância a Radiação/efeitos dos fármacos , Tolerância a Radiação/genéticaRESUMO
Novel coronavirus (nCoV) belongs to the Coronaviridae family, which includes the virus that causes SARS, or severe acute respiratory syndrome. However, infection source, transmission route, and host of nCoV have not yet been thoroughly characterized. In some cases, nCoV presented a limited person-to-person transmission. Therefore, early diagnosis of nCoV may be of importance for reducing the spread of disease in public. Methods for nCoV diagnosis involve smear dyeing inspection, culture identification, and real-time PCR detection, all of which are proved highly effective. Here, we performed a meta-analysis to evaluate the effectiveness of real-time PCR for diagnosing nCoV infection. Fifteen articles conformed to the inclusion and exclusion criteria for further meta-analysis on the basis of a wide range of publications searched from databases involving PubMed, EMBASE, Web of Science, Medline, ISI. We analyzed the stability and publication bias as well as examined the heterogeneity inspection of real-time PCR detection in contrast to smear staining and culture identification. The fixed-effect model was adopted in our meta-analysis. Our result demonstrated that the combination of real-time PCR and smear diagnostics yielded an odds ratio (OR) = 1.91, 95% confidence interval (CI) = 1.51-2.41, Z = 5.43, P < 0.05, while the combination of real-time PCR and culture identification yielded OR = 2.44, 95%CI = 1.77-3.37, Z = 5.41, P < 0.05. Therefore, we propose real-time PCR as an efficient method that offers an auxiliary support for future nCoV diagnosis.
Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Coronavirus/classificação , Coronavirus/genética , Reação em Cadeia da Polimerase em Tempo Real , Estudos de Casos e Controles , Humanos , Razão de Chances , Viés de Publicação , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sensibilidade e EspecificidadeRESUMO
The aim of this study was to examine the relationship between genetic polymorphisms in DNA ligase 1 (LIG1) and non-small cell lung cancer (NSCLC) susceptibility and radiosensitivity in a Chinese population. This was a case-control study that included 352 NSCLC patients and 448 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism analysis was conducted to detect HaeIII polymorphisms in exon 6 of the LIG1 gene in this popula-tion. This information was used to observe the effects of radiation in pa-tients with different genotypes in order to determine the genotypes as-sociated with radiosensitivity. The CC genotype and C allele frequency were significantly higher in the NSCLC group than in the control group (P = 0.012 and P = 0.023, respectively). The relative risk of experienc-ing NSCLC was 2.55 [95% confidence interval (CI), 1.12-3.98] for CC homozygous patients and 0.87 (95%CI, 0.46-1.88) for AA homozygous patients. Analysis of LIG1 genetic polymorphisms and radiosensitiv-ity of NSCLC patients showed that AA homozygous patients were sig-nificantly more radiosensitive than the control group (AA vs AC, P = 0.014; AA vs CC, P < 0.001; AC vs CC, P = 0.023). Therefore, the LIG1 CC genotype was associated with susceptibility to NSCLC, and the AA genotype demonstrated increased radiosensitivity compared to the AC and CC genotypes.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , DNA Ligases/genética , Raios gama/uso terapêutico , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Estudos de Casos e Controles , DNA Ligase Dependente de ATP , Éxons , Feminino , Expressão Gênica , Frequência do Gene , Homozigoto , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Tolerância a RadiaçãoRESUMO
OBJECTIVE: To determine whether the specific genotype of exon 19 deletion has a better survival outcome than that of exon 21 substitution in advanced lung adenocarcinoma with EGFR mutant patients that were treated with EGFR-TKIs as second-line therapy after first-line chemotherapy. METHODS: Between April 1, 2010 and December 31, 2012, the detailed clinical information of 128 patients was screened from the hospital information database of the First Affiliated Hospital and the Third Affiliated Hospital of Kunming Medical University by inclusion/exclusion criteria. Then, a telephone follow-up and a review of all patients' image data were done to obtain the survival information of all patients. After that, all patients' data were processed by IBM(®) SPSS(®) version 19.0. RESULTS: There were correlations between EGFR mutation status, gross tumor type and PFS or OS according to the Kaplan-Meier survival analyses and log-rank tests. The exon 19 deletions had significantly better survival outcomes in comparison to exon 21 substitutions (median PFS: 8.1 vs. 6.8 months, P = 0.002; median OS: 17.6 vs. 12.5 months, P = 0.000). Stratification analyses of PFS and OS revealed that exon 19 deletions had a survival superior to exon 21 substitutions. CONCLUSION: Compared with L858R mutation, the genotype of exon 19 deletion had a better survival outcome in terms of PFS and OS in patients with advanced lung adenocarcinoma treated with EGFR-TKIs as second-line therapy after first-line chemotherapy.
Assuntos
Adenocarcinoma/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Éxons/genética , Neoplasias Pulmonares/genética , Mutação/genética , Deleção de Sequência , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Éteres de Coroa/administração & dosagem , Cloridrato de Erlotinib/administração & dosagem , Feminino , Seguimentos , Gefitinibe , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/administração & dosagem , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
The objective of the current study was to assess the utility of 64-row helical computed tomography angiography (CTA) in the evaluation of extremity vascular traumas. The extremities from 17 clinical cases of suspected traumatic vascular damage were evaluated using 64-row helical CTA. To evaluate extremity vascular traumas using CTA, volume rendering, multiple planar reconstruction, and curved planar reconstruction technology were applied to accurately and rapidly indicate the type and extent of blood vessel damage, as well as any relationship with injuries to adjacent bones, joints, soft tissue swelling, or hematomas. The types of extremity vascular traumas evaluated included damaged arteries, artery spasms or block, blood vessels shifted because of pressure, pseudo aneurysms, arteriovenous fistula, and vein occlusion. The results of the study indicated that 64-row helical CTA could be highly efficient and accurate in the evaluation of extremity vascular traumas, and could aid in making clinical assessments.
Assuntos
Angiografia/métodos , Extremidades/diagnóstico por imagem , Tomografia Computadorizada Espiral/métodos , Lesões do Sistema Vascular/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fêmur/irrigação sanguínea , Humanos , Artéria Ilíaca/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Ruptura , Adulto JovemRESUMO
Increasing evidence has indicated that microRNAs are involved in the pathogenesis of cardiac hypertrophy. However, whether miR-96 is involved in heart diseases, particularly cardiac hypertrophy, remains unclear. In this study, we found that miR-96 is a negative regulator of cardiac hypertrophy. In primary cardiomyocytes, overexpression of miR-96 inhibited phenylephrine-induced cardiomyocyte hypertrophy and decreased the mRNA expression of cardiac hypertrophy markers such as atrial natriuretic factor and ß-myosin heavy chain. Interestingly, we found that growth factor receptor-bound 2 is a direct target of miR-96, which is a negative regulator of cardiac hypertrophy. Overexpression of miR-96 in cardiomyocytes led to reduced growth factor receptor-bound 2 expression. More importantly, miR-96 repressed the extracellular-regulated protein kinase signaling pathway by targeting growth factor receptor-bound 2 in cardiomyocytes. Our data demonstrate that miR-96 is a negative regulator of cardiac hypertrophy and extracellular-regulated protein kinase signaling, thus offering a new therapeutic strategy for cardiac hypertrophy.