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Objectives: Breast cancer is an important women's malignancy with high cancer-related deaths worldwide. Drug resistance lowers the treatment efficacy in this malignancy. This study aimed to explore the underlying mechanisms of histone deacetylase (HDAC) inhibitor trichostatin A (TSA) to overcome resistance to tamoxifen in breast cancer cells. Materials and Methods: Tamoxifen-resistance in MCF-7 breast cancer cells was simulated. MTT assay was used to detect the cytotoxic effects of HDAC inhibitor and PI3K inhibitor on the cancer cells. Trans-well assay was applied to evaluate the invasion and migration of the treated cancer cells. Flow cytometer assay was also applied to evaluate cell cycle phases in the treated cancer cells. Finally, expression of vascular endothelial growth factor (VEGF), E-cadherin, Vimentin, phosphorylated phosphatidylinositol kinase (p-PI3k), phosphorylated protein kinase B (p-AKT), and phosphorylated mammalian target protein of rapamycin (p-mTOR) was evaluated by western blotting. Results: The obtained results indicated that HDAC inhibitor treatments significantly decreased viability, migration, and invasion in the cancer cells. Furthermore, the frequency of the treated cancer cells significantly increased in the S phase as well as significantly decreasing in the G2/M phase of the cell cycle. Moreover, HDAC inhibitor modified levels of VEGF, E-cadherin, Vimentin, p-PI3k, p-AKT, and p-mTOR proteins. However, HDAC inhibitor combined with PI3K inhibitor exerts more profound effects on the cancer cells as compared to HDAC inhibitor monotherapy. Conclusion: HDAC inhibitors inhibited the survival of breast cancer drug-resistant cells, invasion, migration, and angiogenesis by inhibiting the PI3k/Akt/mTOR signaling pathway.
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Background: Early surgical closure is warranted to prevent aortic valve lesion and aortic regurgitation (AR) in intracristal ventricular septal defects (icVSDs). Experiences for transcatheter device closure of icVSDs are still limited. Our objectives are to investigate AR progression following transcatheter closure of icVSDs in children and to explore the risk factors for AR progression. Methods and results: From January 2007 to December 2017, 50 children with icVSD who had successfully undergone transcatheter closure were enrolled. With 4.0 (interquartile range: 3.0-6.2) years of follow-up, AR progression was observed in 20% (10/50) of patients after icVSD occlusion, among which 16% (8/50) remained in mild level and 4% (2/50) evolved to moderate. None progressed to severe AR. Freedom from AR progression was 84.0%, 79.5%, and 79.5% at 1, 5, and 10 years of follow-up. A multivariate Cox proportional-hazards model revealed that x-ray exposure time [hazard ratio (HR): 1.11, 95% confidence interval (CI): 1.04-1.18, P = 0.001] and the ratio of pulmonary to systemic blood flows (HR: 3.38, 95% CI: 1.11-10.29, P = 0.032) were independent predictors for AR progression. Conclusions: Our study suggested that transcatheter closure of icVSD in children is safe and feasible in mid- to long-term follow-up. No serious AR progression occurred after icVSD device closure. Greater left-to-right shunting and longer x-ray exposure time were both risk factors for AR progression.
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Background: Pulmonary artery stenosis is often associated with congenital heart disease. The aim of the study was to evaluate the efficacy and safety of stenting for branch pulmonary artery stenosis using a biodegradable nitride iron stent (IBS® Angel™) and right ventricular systolic and diastolic function. Methods: From July 2021 to February 2022, a total of 11 cases (ages ranged from 36 to 86 months old) were included in this pre and post-intervention, prospective, cohort and preclinical study. All cases underwent transthoracic echocardiographic (TTE), chest radiography, along with computed tomography (256-slice scanner, multiple-detector) and right heart catheterization. Different types of biodegradable nitride iron stents were implanted. TTE was performed serially 1 day, 1 month and 3 months after the procedure to evaluate the rate of restenosis and right ventricular function. Results: Stenting was successful in 11 patients. There were no major adverse cardiovascular events related to the device or to the procedure. Blood perfusion in the branch pulmonary artery was improved immediately. At follow-up, there was no significant restenosis that required re-intervention. None of the patients suffered from in-stent thrombosis, vascular embolism, stent displacement or heart failure. Compared with normal values, there were statistical with regards to FAC, E/A and E'/A'. Furthermore, we found that TAPSE correlated significantly with pulsed Doppler S wave (p = 0.008) and left ventricular ejection fraction (p < 0.01). The early trans-tricuspid inflow velocities E/E' (tissue doppler at the lateral tricuspid annulus) correlated significantly with E'/A' (p = 0.009). FAC and E'/A' were statistically different from those prior to stenting (p = 0.041 and p = 0.035) when tested one month postoperatively. At three months postoperatively, only E/A showed a statistical difference (p = 0.015). Conclusion: Our analysis suggests that biodegradable nitride iron stents are feasible, safe, and effective in children. Some small improvements were observed in right ventricular systolic and diastolic function after successful transcatheter intervention, although change was not statistically significant due to the small sample number. (A clinical Trial to Evaluate the Safety and Efficacy of IBS Angel in Patients With Pulmonary Artery Stenosis (IRIS); NCT04973540).
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OBJECTIVES: To observe and analyze the long-term change of different types of arrhythmias after transcatheter closure of perimembranous ventricular septal defect (pmVSD). METHODS: We retrospectively collected the data of patients who underwent pmVSD closure in our institution from March 2002 to December 2010. RESULTS: One hundred thirty-nine patients met the inclusion criteria, of which 265 (25.5%) had early arrhythmia. They were classified into two categories: conduction abnormality (191/1039; 18.4%) and origin abnormality (94/1039; 9.0%), including 20 patients with both types of arrhythmias. The median follow-up time was 84.5 months, and 103 patients (103/191; 53.9%) with early conduction block got permanent arrhythmias, while only three patients (3/94; 3.2%) with early anomalous origin arrhythmias still had an abnormal electrocardiogram. Serious arrhythmias (28/1039; 2.7%), including II° atrioventricular block (AVB), III° AVB, and complete left bundle branch block (CLBBB), can appear immediately in the early postoperative period (21 patients) or in the late outset (seven patients) after several months or even years (6 months to 8.3 years). Twenty patients (20/21; 95.2%) with serious arrhythmia in the early postoperative period improved after early treatment, but six patients relapsed or worsened during follow-up. At the endpoint, severe arrhythmia persisted in 13 patients, of which four patients got permanent pacemaker implanted, and one patient with recurrent CLBBB died from heart failure. CONCLUSIONS: The probability of delayed CAVB or bundle branch block after VSD closure is low but often occurs several years after surgery. Therefore, long-term ECG follow-up should last for several years or even decades. Serious arrhythmias that appear early after transcatheter pmVSD closure may impose a risk of recurrence although they have been cured already. Close attention should be paid to the changes of cardiac function in patients with CLBBB after VSD closure, and the severity of such arrhythmia should be taken seriously and reexamined.
