ABSTRACT
The NOTCH2 gene plays a role in the development of many tumors. Deltex E3 ubiquitin ligase 3 (DTX3) was identified as a novel E3 ligase for NOTCH2 and as a potential therapeutic target for esophageal cancer. However, whether DTX3 could regulate NOTCH2 to suppress the progression of esophageal carcinoma remains unknown. In our study, NOTCH2 had higher expression in human esophageal carcinoma cell lines compared to normal human esophageal epithelial cell line, and ablation of NOTCH2 suppressed the proliferation and migration of esophageal carcinoma cells. A novel E3 ligase for NOTCH2 was identified by yeast two-hybrid (Y2H) screening, and DTX3 promoted the ubiquitination and degradation of NOTCH2. Further study showed that DTX3 overexpression suppressed the proliferation and tumorigenicity of human oesophageal carcinoma cells. The analysis of tissue samples from patients revealed that the expression of NOTCH2 was high while the expression of DTX3 was low in esophageal cancer. Furthermore, the expression of DTX3 and NOTCH2 showed a significant negative correlation in human oesophageal cancer samples. Our study suggested that the DTX3-NOTCH2 axis plays an important role in the progression of esophageal cancer, and DTX3 acts as an anti-oncogene in esophageal carcinoma, potentially offering a therapeutic target for esophageal cancer.
Subject(s)
Esophageal Neoplasms/pathology , Receptor, Notch2/chemistry , Receptor, Notch2/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Animals , Cell Line, Tumor , Cell Movement , Cell Proliferation , Disease Progression , Esophageal Neoplasms/genetics , Esophageal Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Humans , Male , Mice , Neoplasm Invasiveness , Neoplasm Transplantation , Proteolysis , Signal Transduction , UbiquitinationABSTRACT
BACKGROUND: Operative stabilization is frequently used in the clinical treatment of multiple rib fractures (MRF); however, no ideal material exists for use in this fixation. This study investigates a newly developed biodegradable plate system for the stabilization of MRF. METHODS: Silk fiber-reinforced polycaprolactone (SF/PCL) plates were developed for rib fracture stabilization and studied using a canine flail chest model. Adult mongrel dogs were divided into three groups: one group received the SF/PCL plates, one group received standard clinical steel plates, and the final group did not undergo operative fracture stabilization (n = 6 for each group). Radiographic, mechanical, and histologic examination was performed to evaluate the effectiveness of the biodegradable material for the stabilization of the rib fractures. RESULTS: No nonunion and no infections were found when using SF-PCL plates. The fracture sites collapsed in the untreated control group, leading to obvious chest wall deformity not encountered in the two groups that underwent operative stabilization. CONCLUSIONS: Our experimental study shows that the SF/PCL plate has the biocompatibility and mechanical strength suitable for fixation of MRF and is potentially ideal for the treatment of these injuries.
Subject(s)
Flail Chest/surgery , Rib Fractures/surgery , Thoracic Injuries/surgery , Absorbable Implants , Animals , Antibiotic Prophylaxis , Bone Plates , Disease Models, Animal , Dogs , Flail Chest/diagnostic imaging , Intercostal Muscles/surgery , Postoperative Complications/prevention & control , Radiography , Rib Fractures/diagnostic imaging , Thoracic Injuries/diagnostic imagingABSTRACT
BACKGROUND: Second-generation drug-eluting stents (DES) are purported to have a lower risk of stent thrombosis than first-generation DES. However, few studies have examined the frequency of late stent thrombosis (LST) and very LST (VLST) in patients with second-generation DES, and the safety of discontinuation of dual antiplatelet therapy (DAPT) remains controversial. METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Library, and clinicaltrials.gov to identify all reported cases of definite LST and VLST in patients with second-generation DES. Inclusion was restricted to cases with zotarolimus-eluting stents (ZES) and everolimus-eluting stents (EES) in which the time from percutaneous coronary intervention and time from discontinuation of DAPT to LST/VLST was reported. RESULTS: A total of 26 cases (15 ZES and 11 EES) in 11 publications were included. We identified 17 cases of LST and 9 cases of VLST. The median time from percutaneous coronary intervention to LST/VLST in ZES patients was 121 days (interquartile range [IQR], 89-292) and in EES patients was 364 days (IQR, 269-504). For the 5 patients who discontinued taking acetylsalicylic acid and clopidogrel simultaneously, the median time to event was 20 days (IQR, 10-60). For the 7 patients who discontinued taking clopidogrel but continued taking acetylsalicylic acid, the median time to event was 190 days (IQR, 135-303). CONCLUSIONS: With only a few reported cases of LST/VLST in the literature, available data suggest that thrombotic events might be rare with second-generation DES. Moreover, LST/VLST appears to occur later after DAPT discontinuation in patients with second-generation DES than in those with first-generation DES.
