ABSTRACT
OBJECTIVE: To detect the expression of microRNA-556-3p in esophageal cancer (EC) tissues and to elucidate the mechanisms underlying microRNA-556-3p in promoting EC progression. PATIENTS AND METHODS: QRT-PCR (quantitative Real-Time Polymerase Chain Reaction) was performed to detect microRNA-556-3p expression in 65 cases of EC tissues, 30 cases of normal esophageal tissues and EC cell lines. The overall survival (OS) of EC patients was calculated based on the 10-year follow-up data. For in vitro experiments, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell assay were performed to evaluate the effect of microRNA-556-3p on the proliferative and invasive abilities of EC cells. The effect of microRNA-556-3p on DAB2IP and MAPK pathway was determined by Western blot and qRT-PCR. The binding condition between microRNA-556-3p and DAB2IP was further confirmed by Luciferase reporter gene assay. RESULTS: MicroRNA-556-3p expression was upregulated in EC tissues than that of paracancerous tissues. EC patients with higher expression of microRNA-556-3p presented a shorter OS than those with lower expression. Moreover, microRNA-556-3p overexpression in EC cells remarkably promoted cell viability. Upregulated microRNA-556-3p in Eca109 and Eca7906 cell lines markedly increased cell proliferation and invasion. The expression level of DAB2IP was negatively regulated by microRNA-556-3p verified by the Luciferase reporter gene assay. CONCLUSIONS: MicroRNA-556-3p blocked the translation of DAB2IP at mRNA level by directly binding to 3'UTR of DAB2IP, thereafter enhancing the proliferation of Eca109 and Eca7906 cells. MicroRNA-556-3p promoted the occurrence and development of EC. Our study provided a new theoretical basis and therapeutic target for EC treatment.
Subject(s)
Esophageal Neoplasms/metabolism , MicroRNAs/metabolism , ras GTPase-Activating Proteins/metabolism , 3' Untranslated Regions , Binding Sites , Cell Line, Tumor , Cell Movement , Cell Proliferation , Disease Progression , Esophageal Neoplasms/genetics , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Female , Gene Expression Regulation, Neoplastic , Humans , Male , MicroRNAs/genetics , Middle Aged , Mitogen-Activated Protein Kinases/metabolism , Neoplasm Invasiveness , Prognosis , Retrospective Studies , Signal Transduction , ras GTPase-Activating Proteins/geneticsABSTRACT
AIM: To determine the efficacy of dual Y-shaped covered airway stents to treat thoracic stomach-right main bronchus fistulae. MATERIAL AND METHODS: Fifteen patients who developed thoracic stomach-right main bronchus fistula after oesophageal cancer resection and postoperative irradiation were retrospectively analysed. All fistulae were close to the right upper lobe bronchus. Two Y-shaped covered airway stents were designed for each patient. Under radiographic guidance, one stent was placed from the right main bronchus into the bifurcation of upper lobe and intermediate bronchus, the other was placed from the trachea into both main bronchi. RESULTS: All fistulae were closed immediately after stenting. All patients could eat a semi-solid diet. The symptom of coughing while lying down resolved in all patients, and no complications, such as airway bleeding or pneumothorax, occurred. The average survival time was 26.65 months (range 2-40 months, 11 patients were still alive at the study end). Two patients died of tumour recurrence. Another two patients died of pulmonary infections. In one of these patients, there was a long delay between symptom onset and stenting. In the other patient, a small rupture occurred in the silicone membrane covering the stent, which allowed the leakage of gastric contents into the lung. CONCLUSION: Dual Y-shaped covered airway stent placement is feasible and safe to treat thoracic stomach-right main bronchus fistulae. Improvements to the material covering the stents is required.
Subject(s)
Bronchial Fistula/surgery , Gastric Fistula/surgery , Stents , Adult , Aged , Female , Humans , Male , Middle Aged , Prosthesis Design , Retrospective Studies , Treatment OutcomeABSTRACT
Estrogen receptor-related receptor-α (ERRα) is an orphan member of the nuclear receptor superfamily that interacts with peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) to stimulate vascular endothelial growth factor (VEGF) expression and angiogenesis in a hypoxia-inducible factor-1α-independent pathway. Although it is not regulated by any natural ligand, the action of ERRα can be blocked by the synthetic molecule XCT790. In the present study, Sprague-Dawley rats were randomly allocated to a sham group, injury-saline group or injury-XCT90 group. A modified Allen's weight-drop method was applied to induce the acute traumatic spinal cord injury (SCI) model in these rats, and an injection of XCT790 was administered every 24h, starting half an hour after the SCI contusion. Histological analyses revealed that XCT790 significantly aggravated tissue damage and decreased the number of ERRα-positive cells at 1, 3 and 7 days after SCI. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) analyses also indicated that XCT790 dramatically repressed the expression of ERRα, thus reducing the expression of VEGF and angiopoietin-2 (Ang-2) throughout the duration of the experiment, but the expression of PGC-1α was not affected. Immunofluorescence analyses indicated that vascular density and endothelial cell proliferation were decreased in the injury-XCT90 group compared with the injury-saline group. These results suggest that ERRα is involved in mediating angiogenesis after SCI in the rat traumatic SCI model.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Neovascularization, Pathologic/drug therapy , Nitriles/pharmacology , Receptors, Estrogen/metabolism , Spinal Cord Injuries/drug therapy , Thiazoles/pharmacology , Angiopoietin-2/metabolism , Animals , Cell Proliferation/drug effects , Disease Models, Animal , Endothelial Cells/drug effects , Endothelial Cells/pathology , Endothelial Cells/physiology , Male , Neovascularization, Pathologic/pathology , Neovascularization, Pathologic/physiopathology , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Random Allocation , Rats, Sprague-Dawley , Receptors, Estrogen/antagonists & inhibitors , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology , Transcription Factors/metabolism , Vascular Endothelial Growth Factor A/metabolism , ERRalpha Estrogen-Related ReceptorABSTRACT
BACKGROUND: Animal models for the study of tendinopathy and bone-tendon (B-T) junction repair have been established in the past for sports medicine research. As healing at the B-T junction is difficult and sometimes delayed, establishing a delayed B-T healing experimental model is therefore essential to study the efficacy of potential biophysical and biological interventions for treatment of B-T junction healing. OBJECTIVE: To test the hypothesis that a delay in B-T healing could be modelled by shielding the B-T healing interface for the initial few weeks. METHODS: Using an established partial patellectomy model in rabbits, the B-T healing interface was shielded with a latex slice for the first 4 postoperative weeks in mature female rabbits. The characteristics of delay in B-T repair (n = 10) compared with controls (n = 10) were evaluated at 8 and 12 postoperative weeks. RESULTS: Radiology showed consistent delay in osteogenesis at the healing interface in all samples in the delayed healing group; growth of new bone was only 25.8% and 50.1% of that in the control group at weeks 8 and 12, respectively. Bone mineral density was 56.0% lower in the delayed healing group at week 8, but this difference diminished at week 12. The quality of B-T healing was poor in the delayed healing group, with 22.9% and 24.2% lower failure load than the control group at weeks 8 and 12, respectively. The healing quality was also reflected by histological findings. CONCLUSIONS: A delayed B-T healing experimental model was established for the first time for future sports medicine research.
