ABSTRACT
LCN2 is involved in various cellular functions, including transport of small hydrophobic molecules, protection of MMP9 from proteolytic degradation, and regulating innate immunity. LCN2 is elevated in multiple human cancers, frequently being associated with tumor size, stage, and invasiveness. Our previous studies have shown that LCN2 expression could be induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in esophageal squamous cell carcinoma (ESCC) by the binding of five nucleoproteins (MISP, KLF10, KLF15, PPP1R18, and RXRß) at a novel TPA-responsive element (TRE), at -152~-60 bp of the 5' flanking region of the LCN2 promoter. However, much is unknown about whether these proteins can respond to TPA stimulation to regulate LCN2 transactivation and which cell signaling pathways mediate this process. In this study, expression plasmids encoding these five nucleoproteins were stably transfected into EC109 cells. Then, stable transfectant was characterized by a Dual-Luciferase Reporter Assay System. RT-PCR, real-time PCR, western blotting, specific kinase inhibitor treatment, and bioinformatics analyses were applied in this study. We found that MISP, KLF10, KLF15, PPP1R18, and RXRß proteins could strongly respond to TPA stimulation and activate LCN2 transcriptional expression. MEK, ERK, JNK, and P38 kinases were involved in the LCN2 transactivation. Furthermore, the MEK-ERK signal pathway plays a major role in this biological process but does not involve PKCα signaling.
Subject(s)
Carcinoma, Squamous Cell/genetics , Esophageal Neoplasms/genetics , Lipocalin-2/genetics , Neoplasm Proteins/genetics , Transcription, Genetic , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma , Gene Expression Regulation, Neoplastic/drug effects , Humans , MAP Kinase Signaling System/drug effects , Matrix Metalloproteinase 9/genetics , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Promoter Regions, Genetic , Protein Kinase C-alpha/genetics , Signal Transduction/drug effects , Signal Transduction/genetics , Tetradecanoylphorbol Acetate/pharmacologyABSTRACT
OBJECTIVE: To explore the feasibility and safety of using tissue-type plasminogen activator (t-PA) to prevent graft restenosis after coronary artery bypass grafting (CABG). METHODS: In this prospective observational study, 37 patients underwent CABG between June 2009 and May 2013. These patients were grouped according to the anti-coagulation strategy after surgery: t-PA (n = 12) and conventional treatments (n = 25). In the t-PA group, the patients received acetylsalicylic acid (ASA) and clopidogrel plus intravenous infusion of t-PA (0.25 mg/kg/day) starting at 24 h after surgery and that lasted for 3 days. In the conventional group, the patients received only ASA and clopidogrel. 64-row spiral computed tomographic coronary angiography was performed at 1 week, 1, and 3 months after surgery to evaluate the patency of the graft vessel. RESULTS: The mean stenosis severity of the saphenous vein grafts was lower in the t-PA group compared with the conventional group at 3 months after surgery (p < 0.05), but there was no significant difference at 1 week and 1 month (p > 0.05). The patency rate of the grafts was not significantly different between the two groups at 1 week, 1, and 3 months after surgery (p > 0.05). CONCLUSION: Early application of t-PA after CABG was feasible and safe, and might help prevent early restenosis of SV grafts. Additional clinical randomized trials are necessary to address this issue.
Subject(s)
Coronary Artery Bypass/adverse effects , Graft Occlusion, Vascular/drug therapy , Graft Occlusion, Vascular/prevention & control , Tissue Plasminogen Activator/administration & dosage , Aged , Aspirin/administration & dosage , Blood Coagulation/drug effects , Clopidogrel , Coronary Angiography , Female , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/genetics , Humans , Male , Middle Aged , Prospective Studies , Ticlopidine/administration & dosage , Ticlopidine/analogs & derivatives , Ticlopidine/chemistry , Tissue Plasminogen Activator/chemistry , Treatment OutcomeABSTRACT
OBJECTIVE: To compare the quality of life in patients with prevertebral or retrosternal reconstruction after cervical tubular gastroesophagostomy. METHODS: A total of 167 patients enrolled in this prospective study from July 2008 to June 2012 in Shantou Central Hospital, and divided into prevertebral route group(85 cases) and retrosternal route group(82 cases) according to the random number table method. Quality of life questionnaire was investigated 1, 3, 6, 9, and 12 months after operation respectively. RESULTS: The incidence of anastomotic stenosis was lower in the prevertebral route group (P<0.05). However, the differences in perioperative general conditions between the two groups were not statistically significant(all P>0.05). One hundred and forty-nine patients completed the postoperative quality of life questionnaire. Dysphagia and swallowing retching symptom were better, while acid reflux and heartburn symptom were more serious in prevertebral route group as compared to retrosternal route group(all P<0.05). Overall quality of life score difference between the two groups was not statistically significant(P>0.05). CONCLUSIONS: For digestive tract reconstruction after resection of esophageal cancer, tubular gastroesophagostomy by prevertebral or retrosternal route both can obtain better quality of life after surgery. Swallowing function after surgery of the former is superior to the latter, but the reflux symptoms is more serious. Therefore the two mehods have their own advantages and disadvantages, and the choice of route should be depended on clinical experience and patient condition.
