RESUMO
Epidermal growth factor-like domain multiple 7 (EGFL7) is an important sport stimulating factor and motility related factors significantly enhanced the tumor cell metastasis and overexpressed in many cancers, including hepatocellular carcinoma (HCC), associated with tumorigenesis. However, the molecular mechanism by which EGFL7 regulates HCC cell proliferation and apoptosis and the correlation between EGFL7 and cyclin-dependent kinases regulatory subunit 2 (CKS2), which is essential for biological function, have not fully explained. In this study, EGFL7 and CKS2 expression in patients with HCC was measured by real-time polymerase chain reaction and immunohistochemistry. After HCC cells respectively transfected with pLKO.1-EGFL7-shRNA, pLVX-Puro-EGFL7 recombined vector or CKS2 small interfering RNA, cell counting kit-8 and flow cytometry was performed to examine the cell proliferation and apoptosis, respectively, and the expression of ß-catenin, CKS2, CDK2, and cleaved caspase-3 was measured by Western blot analysis. We found that EGFL7 and CKS2 were overexpressed in HCC tissues and a positive correlation was found between them. EGFL7 knockdown markedly inhibited proliferation and promoted apoptosis of HCC cells, along with decreased expression of CKS2 and CDK2, but increased cleaved caspase-3 expression, while EGFL7 overexpression showed an opposite effect. EGFL7 silencing in nude mice also showed decreased tumor growth and altered protein expression similar to its effect in HCC cells in vitro. Importantly, CKS2 silencing significantly inhibited EGFL7-induced HCC cell proliferation and protein expression, and Wnt/ß-catenin signaling pathway inhibitor IWR-1-endo significantly inhibited CKS2 expression in HCC cells. Taken together, EGFL7 promotes HCC cell proliferation and inhibits cell apoptosis through increasing CKS2 expression by activating Wnt/ß-catenin signaling.
Assuntos
Quinases relacionadas a CDC2 e CDC28/genética , Carcinoma Hepatocelular/genética , Proteínas de Transporte/genética , Proteínas de Ciclo Celular/genética , Fatores de Crescimento Endotelial/genética , Neoplasias Hepáticas/genética , Apoptose/genética , Proteínas de Ligação ao Cálcio , Carcinoma Hepatocelular/patologia , Proliferação de Células/genética , Família de Proteínas EGF , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Via de Sinalização Wnt/genéticaRESUMO
BACKGROUND: Percutaneous radiofrequency thermocoagulation through the foramen rotundum (FR) is a new approach for the treatment of V2 trigeminal neuralgia (TN). OBJECTIVES: This study aimed to compare the efficacy and safety of the FR approach with that of the foramen ovale (FO) approach. STUDY DESIGN: Nonrandomized controlled clinical trial. SETTING: The study was conducted at Huaian Hospital of Huaian City, Huaian, China. METHODS: From July 2014 to December 2016, 80 consecutive patients with V2 TN were prospectively assigned into the FO group (n = 40) or the FR group (n = 40). All radiofrequency thermocoagulation procedures were performed under the guidance of digital subtraction angiography (DSA). Patients in the FO group were treated with Gasserian ganglion ablation through the Hartel approach. Patients in the FR group received ablation of the maxillary nerve at the internal opening of the FR. Facial pain was evaluated using the Visual Analog Scale preoperatively and postoperatively at 1 week, 6 months, and 1 year. RESULTS: All surgical procedures were successfully completed using DSA guidance. The FR group had no facial pain at postoperative 1 week, 6 months, and 1 year. The facial fain was not relieved in 4 patients of the FO group. They were treated with radiofrequency thermocoagulation of the maxillary nerve through the FR and maintained painless at postoperative 1 week, 6 months, and 1 year. At postoperative 1 year, another 3 patients relapsed in the FO group. The incidences of facial numbness and swelling did not differ significantly between the 2 groups (all P > 0.05). There was no postoperative corneal involvement or masticatory weakness in the FR group. However, corneal involvement and masticatory weakness occurred postoperatively in 22 (55%) patients and 31 (77.5%) patients in the FO group. The FR group had significantly shorter operation time than the FO group (19.3 ± 5.9 vs. 32.7 ± 8.7 minutes; P < 0.05). LIMITATIONS: We were unable to avoid the V1 and V3 branches, despite multiple adjustments of the needed position in 35 of the 40 patients in this group. CONCLUSIONS: For the treatment of V2 TN, thermocoagulation of the maxillary nerve through the FR had better efficacy and fewer complications in comparison with the Gasserian ganglion ablation through the FO. KEY WORDS: Neuralgia, pain, radiology, facial pain.
Assuntos
Eletrocoagulação/métodos , Forame Oval/diagnóstico por imagem , Terapia por Radiofrequência/métodos , Neuralgia do Trigêmeo/diagnóstico por imagem , Neuralgia do Trigêmeo/terapia , Adulto , Idoso , Angiografia Digital/métodos , China/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Neuralgia do Trigêmeo/epidemiologiaRESUMO
This study explored the predictive value of serum vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) levels combined with enhanced magnetic resonance imaging (MRI) in hepatocellular carcinoma (HCC) patients after transcatheter arterial chemoembolization (TACE). One hundred and seventeen patients who received TACE from June 2010 to December 2012 in our hospital were included in this study. Serum VEGF and CRP levels before and after TACE were determined by ELISA and single immunodiffusion method for analyzing the association of serum levels with pathological features. Enhanced MRI was utilized before and after TACE to measure tumor size and ADC value in enhanced region and non-enhanced region. MRI data were combined with serum VEGF and CRP levels to analyze the predictive value in efficacy and prognosis for HCC patients after TACE. The serum VEGF and CRP levels after TACE were increased, but can return to normal levels in a certain time. VEGF and CRP levels were not statistically associated with tumor location, tumor staining or presence of membrane (all P > 0.05), but closely correlated with combined portal vein tumor thrombus, combined arteriovenous fistula and distant metastasis (all P < 0.05). Low levels of serum VEGF and CRP, small tumor size and low ADC value before treatment indicated a better prognosis. The sensitivity and specificity of serum VEGF and CRP levels, tumor size and ADC value were respectively 92.31% and 88.46%, 93.85% and 90.38%, 81.54% and 78.85% as well as 47.69% and 84.62%. Serum VEGF and CRP levels, tumor size and ADC value could predict the efficacy of TACE for HCC patients. Serum VEGF and CRP levels combined with enhanced MRI may serve as markers for efficacy and prognosis evaluation in HCC patients after TACE.