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Down-regulation of long non-coding RNA MEG3 indicates an unfavorable prognosis in non-small cell lung cancer: Evidence from the GEO database
Zhang, ZC;Liu, TT;Wang, K;Qu, X;Pang, ZF;Liu, SR;Liu, Q;Du, JJ
GENE 2017年 630卷 页码:49-58 影响因子:2.319
GENE-EXPRESSION; PROLIFERATION; STATISTICS; VALIDATION; SIGNATURE; APOPTOSIS; HISTOLOGY; P53
Long non-coding RNA (lncRNA) MEG3 (maternally expressed gene 3) is an imprinted gene that suppresses cells growth in various tumors. However, the association between MEG3 expression and prognosis in non-small cell lung cancer (NSCLC) has not been fully investigated. Seven datasets with 1144 patients were obtained from Gene Expression Omnibus (GEO) database (Affymetrix U133 Plus 2.0 platform). Association between MEG3 and other variables was tested using the chi-squared test. Kaplan-Meier survival analysis was carried out to explore the association between MEG3 expression and overall survival (OS)/progression free survival (PFS). Results of univariate and multivariate Cox regression analysis were represented in HR and 95%CI form. Summarized results and publication bias were showed by forest plots and funnel plots respectively. Differential expression of MEG3 was related to stage (GSE31210OS and GSE3121OPFS), histology (GSE29013OS and GSE29013PFS) and gender (GSE29013PFS). In summary, low MEG3 expression was associated with shorter long-term survival time in several datasets (GSE3141 (p = 0.039), GSE30219 (p = 0.008) for OS and GSE30219 (p = 0.048) for PFS). We found that MEG3 was an independent prognostic factor in GSE30219 for PFS (HR 0.666, 95%CI 0.458-0.969, p = 0.033). The summarized results suggested that low MEG3 expression was a poor prognostic factor in NSCLC (HR = 0.77, 95%CI 0.63-0.95). Specifically, the association between low MEG3 expression and poor prognosis was markedly significant in younger patients (<= 60 years old) (HR0.602, 95%CI 0.417-0.867, p = 0.007). These findings indicate that MEG3 could be a novel prognostic factor for NSCLC patients.
Impact of serum SP-A and SP-D levels on comparison and prognosis of idiopathic pulmonary fibrosis: A systematic review and meta-analysis
Wang, K;Ju, Q;Cao, J;Tang, WZ;Zhang, J
MEDICINE 2017年 96卷23期
SURFACTANT-PROTEIN-A; INTERCELLULAR-ADHESION MOLECULE-1; INTERSTITIAL LUNG-DISEASES; ACUTE EXACERBATION; ALVEOLAR MACROPHAGES; PREDICTS SURVIVAL; EPITHELIAL-CELLS; BIOMARKERS; PNEUMONIA; MORTALITY
Background and objective:Idiopathic pulmonary fibrosis (IPF) has a poor prognosis in general; however, it is heterogeneous to detect relative biomarkers for predicting the disease progression. Serum biomarkers can be conveniently collected to detect and help to differentially diagnose IPF and predict IPF prognosis. This meta-analysis aimed to evaluate the use of serum surfactant proteins A and D (SP-A and SP-D) for differential diagnosis and prognosis of IPF.Methods:Relevant articles were searched in PubMed, Embase, and Chinese National Knowledge Infrastructure databases and reviewed by 2 independent readers. Standard mean difference (SMD) and 95% confidence interval (CI) were calculated to assess the difference in serum levels of SP-A/D among patients with IPF, when compared to patients with non-IPF interstitial lung disease (ILD), pulmonary infection, and healthy control. Hazard ratio (HR) and 95% CI were used to compare the relative risk of mortality.Results:Twenty-one articles (totalling 1289 IPF patients) were included in final meta-analysis. Serum SP-A levels were significantly higher in patients with IPF than in patients with non-IPF ILD (SMD: 1.108 [0.584, 1.632], P<.001), or pulmonary infection (SMD: 1.320 [0.999, 1.640], P<.001) and healthy controls (SMD: 2.802 [1.901, 3.702], P<.001). There was no significant difference in serum SP-D levels between patients with IPF and those with non-IPF ILD patients (SMD: 0.459 [-0.000, 0.919], P=.050). Serum SP-D levels were significantly higher in patients with IPF than in patients with pulmonary infection (SMD: 1.308 [0.813, 1.803], P<.001) and healthy controls (SMD: 2.235 [1.739, 2.731], P<.001). Risk of death in patients with IPF and elevated serum SP-A was increased 39% compared to patients with low SP-A groups. Elevated SP-D increased risk by 111% when compared to low SP-D. In acute exacerbation of IPF, serum SP-A/D were higher than those in stable stage. The comparisons and prognosis might be different in Asian and Caucasian patients.Conclusions:Serum SP-A/D detection might be useful for differential diagnosis and prediction of survival in patients with IPF.
ARRB1 enhances the chemosensitivity of lung cancer through the mediation of DNA damage response
Shen, HC;Wang, LG;Zhang, JG;Dong, W;Zhang, TH;Ni, Y;Cao, HX;Wang, K;Li, Y;Wang, YB;Du, JJ
ONCOLOGY REPORTS 2017年 37卷2期 页码:761-767
FLOW-CYTOMETRY; BETA-ARRESTINS; CELL; CARCINOMA; APOPTOSIS; BETA-ARRESTIN-1; EXPRESSION; PROGNOSIS; THERAPY; ASSAY
ARRB1 (also known as beta-arresting) serves as a multifunctional adaptor contributing to the regulation of signaling pathways. ARRB1 may be involved in DNA damage accumulation; however the underlying mechanism involved is unclear. In the present study, non-small cell lung cancer (NSCLC) cell lines (H520 and SK-MES-1) were transfected with ARRB1 plasmids or small interfering ribonucleic acid (siRNA) and received treatment with DNA-damaging agents (cisplatin and etoposide). A mouse xenograft model was used to assess the impact of ARRB1 on the efficacy of cisplatin in vivo. A total of 30 surgically resected NSCLC patients were recruited for the present study and qRT-PCR was performed to determine the mRNA levels in cancer tissues compared with para-carcinoma tissues. Our data showed that DNA damage was abrogated in the ARRB1-knockdown cells and enhanced in the ARRB1-overexpressing cells. ATR and Chk1 were more activated in the ARRB1-overexpressing cells compared to the ARRB1-knockdown cells, followed by increased H2AX phosphorylation. DNA damage and apoptosis were increased in the ARRB1-overexpressing cells treated with cisplatin. These data provided strong evidence that ARRB1 contributes to the response of NSCLC to DNA-damaging agents and is essential for DNA damage response (DDR). ARRB1 may enhance the efficacy of DNA-damaging agents in NSCLC.
Adverse Events and Efficacy of Cixutumumab in Phase II Clinical Trials: A systematic Review and Meta-Analysis
Cao, HX;Cui, LX;Ma, W;Zhu, LH;Wang, K;Ni, Y;Wang, YB;Du, JJ
CLINICAL DRUG INVESTIGATION 2017年 37卷2期 页码:135-153
GROWTH-FACTOR-RECEPTOR; CHILDRENS ONCOLOGY GROUP; CELL LUNG-CANCER; REFRACTORY SOLID TUMORS; SOFT-TISSUE SARCOMA; HUMAN BREAST-CANCER; OPEN-LABEL; MONOCLONAL-ANTIBODY; PEDIATRIC-PATIENTS; INSULIN-RECEPTOR
Background and Objectives Cixutumumab is a monoclonal antibody targeting insulin-like growth factor 1 receptor (IGF1R). We sought to evaluate the efficacy of cixutumumab in the treatment of cancer, and to comprehensively assess the associated adverse events in phase II clinical trials.;-;Methods Data were collected from PubMed, Embase, and Clinicaltrials.gov. The improvement on progression-free survival (PFS) was evaluated by hazard ratio (HR) and 95% confidence intervals (95% CIs). We also carried a meta-analysis to comprehensively evaluate the incidence of adverse events.;-;Results The adverse events that were mentioned most frequently were hyperglycemia, anemia, nausea, fatigue, and thrombocytopenia. The most frequent adverse events were hyponatremia (40.28%), fatigue (35.18%), and skin rash (35.11%). Results showed that cixutumumab treatments did not benefit PFS (HR 1.03, 95% CI 0.83-1.26, p = 0.979). The complete response (CR) was rarely seen in phase II trials.;-;Conclusions Cixutumumab was well tolerated when used alone and in combination therapies, but its antitumor activity was low in the existing phase II clinical trials. An acceptable incidence of adverse effects supports further investigation of this drug, provided that it shows antitumor activity in combination with other drugs.
Gamma-synuclein binds to AKT and promotes cancer cell survival and proliferation
Ma, ZX;Niu, JY;Sun, EL;Rong, XD;Zhang, XX;Ju, YR
TUMOR BIOLOGY 2016年 37卷11期 页码:14999-15005
LUNG-CANCER; MTOR PATHWAY; GENE; KINASE; EXPRESSION; IDENTIFICATION; METASTASIS; RESISTANCE; MUTATION; THERAPY
Hyperactivation of AKT plays a critical role in the survival and proliferation of cancer cells. However, the molecular mechanisms underlying AKT activation remain elusive. Here, we tested the effect of gamma-synuclein, a member of the synuclein family of proteins, on the activation of AKT. We show that the expression level of gamma-synuclein is increased in non-small cell lung cancer (NSCLC) tissues. gamma-Synuclein binds to the protein kinase domain of AKT and promotes its phosphorylation. Overexpression of gamma-synuclein in H157 cells enhances cell proliferation and protects the cells from staurosporine-induced cytotoxicity. Knockdown of gamma-synuclein attenuates AKT activation and cell proliferation induced by epidermal growth factor. The effect of gamma-synuclein is abolished when AKT is depleted. Thus, gamma-synuclein promotes cell survival and proliferation via activating AKT and may play a causal role in the pathogenesis of NSCLC.
Protective effects of drag-reducing polymers in a rat model of monocrotaline-induced pulmonary hypertension
Wang, YL;Hu, F;Mu, XY;Wu, F;Yang, DC;Zheng, GX;Sun, XN;Gong, KZ;Zhang, ZG
BIORHEOLOGY 2016年 53卷1期 页码:13-22 影响因子:0.981
HEMORRHAGIC-SHOCK; ALOE-VERA; DIAGNOSIS; SURVIVAL; REDUCTION; INFUSION; DISEASE; BLOOD
OBJECTIVES: Drag-reducing polymers (DRPs) are blood-soluble macromolecules which may increase blood flow and reduce vascular resistance. The purpose of the present study was to observe the effect of DRPs on monocrotaline-induced pulmonary hypertension (PH) in the rat model.;-;METHODS: A total of 64 male Wistar rats were randomly divided into four groups: Group I (pulmonary hypertension model + DRP treatment); Group II (pulmonary hypertension model + saline treatment); Group III (control + DRP treatment); Group IV (control + saline treatment). After five weeks, comparisons were made of the following indices: survival rate, body weight, blood pressure, right ventricular systolic pressure, right ventricular hypertrophy, wall thickness of pulmonary arteries, the internal diameter of small pulmonary arteries, plasma IL-1 beta and IL-6.;-;RESULTS: The survival rate after 5 weeks varied significantly across all groups (P = 0.013), but the survival rates of Groups I and II were not statistically significantly different. Administration of DRP (intravenous injection twice weekly) attenuated the PH-induced increase in right ventricular systolic pressure and suppressed the increases in right ventricular (RV) weight and the ratio of right ventricular weight to left ventricle plus septum weight (RV/LV + S). DRP treatment also significantly decreased the wall thickness of pulmonary arteries, augmented the internal diameter of small pulmonary arteries, and suppressed increases in the plasma levels of IL-1 beta and IL-6.;-;CONCLUSIONS: DRP treatment with intravenous injection effectively inhibited the development of monocrotaline-induced pulmonary hypertension in the rat model. DRPs may have potential application for the treatment of pulmonary hypertension.
Hispidulin induces mitochondrial apoptosis in acute myeloid leukemia cells by targeting extracellular matrix metalloproteinase inducer
Gao, H;Liu, YJ;Li, K;Wu, TH;Peng, JJ;Jing, FB
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH 2016年 8卷2期 页码:1115-1132
CANCER-CELLS; SIGNALING PATHWAY; RECOGNITION MOLECULE; PANCREATIC-CANCER; ACTIVATING AMPK; DOWN-REGULATION; IN-VITRO; CD147; GROWTH; ANGIOGENESIS
Acute myeloid leukemia (AML) represents a heterogeneous group of hematological neoplasms with marked heterogeneity in response to both standard therapy and survival. Hispidulin, a flavonoid compound that is anactive ingredient in the traditional Chinese medicinal herb Salvia plebeia R. Br, has recently been reported to have anantitumor effect against solid tumors in vitro and in vivo. The aim of the present study was to investigate the effects of hispidulin on the human leukemia cell line in vitro and the underlying mechanisms of its actions on these cells. Our results showed that hispidulin inhibits AML cell proliferation in a dose-and time-dependent manner, and induces cell apoptosis throughan intrinsic mitochondrial pathway. Our results also revealed that hispidulin treatment significantly inhibits extracellular matrix metalloproteinase inducer (EMMPRIN) expression in both tested AML cell lines in a dose-dependent manner, and that the overexpression of EMMPRIN protein markedly attenuates hispidulin-induced cell apoptosis. Furthermore, our results strongly indicated that the modulating effect of hispidulin on EMMPRIN is correlated with its inhibitory effect on both the Akt and STAT3 signaling pathways.
Effect of mu Agonists on Long-Term Survival and Recurrence in Nonsmall Cell Lung Cancer Patients
Wang, K;Qu, X;Wang, Y;Shen, HC;Liu, Q;Du, JJ
MEDICINE 2015年 94卷33期
CIRCULATING TUMOR-CELLS; OPIOID RECEPTOR EXPRESSION; RETROSPECTIVE ANALYSIS; EPIDURAL ANALGESIA; RANDOMIZED-TRIAL; PROSTATE-CANCER; BREAST-CANCER; SURGERY; STATISTICS; ANESTHESIA
Opioids are widely used for postoperative analgesia. Morphine may have an effect on cell replication, migration, and cancer recurrence. However, the association of postoperative mu agonists with outcome of nonsmall cell lung cancer (NSCLC) patients has not been fully investigated.We retrospectively evaluated the impact of postoperative mu agonists on overall survival (OS) and disease-free survival (DFS) in early stage NSCLC patients. Patients and relevant medical information were selected from the Bio-Bank of Shandong Provincial Hospital. Difference of clinicopathologic information in postoperative mu agonists group and no mu agonists group was analyzed by (2) test. Univariate and multivariate Cox regression analysis were conducted and represented as hazards ratio and 95% confidence interval form. The primary endpoint was OS and secondary endpoint was DFS.This retrospective study included 984 consecutive NSCLC patients who underwent surgery between January 2006 and December 2011. No significant difference existed between postoperative mu agonists usage group and no mu agonists usage group in clinicopathologic information except operation type (P=0.041). Postoperative mu agonists usage was related to shorter OS (HR 1.514, 95% CI 1.197-1.916, P=0.001) and shorter DFS (HR 1.415, 95% CI 1.123-1.781, P=0.003) in the multivariate Cox regression model. For the patients who received postoperative chemotherapy or radiotherapy postoperative mu agonists also predict shorter survival (HR 1.437, 95% CI 1.041-1.982, P=0.027). Subgroup analysis showed that administration of postoperative mu agonists was related to shorter OS, especially in males, more smoking, poor differential degree, bilobectomy or pneumonectomy, and stage III subgroup, respectively.Administration of postoperative mu agonists was related to shorter OS and DFS for the NSCLC patients who underwent surgery.
Gastropulmonary Route of Infection and the Prevalence of Microaspiration in the Elderly Patients with Ventilator-Associated Pneumonia Verified by Molecular Microbiology-GM-PFGE
Liu, QH;Zhang, J;Lin, DJ;Mou, XY;He, LX;Qu, JM;Li, HY;Hu, BJ;Zhu, YM;Zhu, DM;Gao, XD
CELL BIOCHEMISTRY AND BIOPHYSICS 2015年 71卷3期 页码:1457-1462
SUBGLOTTIC SECRETION DRAINAGE; MECHANICAL VENTILATION; RISK-FACTORS; PREVENTION; ASPIRATION; METAANALYSIS
Gastropulmonary route of infection was considered to be an important mechanism of ventilator-associated pneumonia (VAP). However there is little evidence to support this assumption. Moreover, the prevalence of microaspiration in elderly ventilated patients was not well understood. To confirm gastropulmonary infection route and investigate the prevalence of microaspiration in elderly ventilated patients using genome macrorestriction-pulsed field gel electrophoresis (GM-PFGE). Patients over 60 years old, expected to receive mechanical ventilation longer than 48 h, were prospectively enrolled from October 2009 to January 2012. Clinical data were collected and recorded until they died, developed pneumonia, or were extubated. Samples from gastric fluid, subglottic secretion and lower respiratory tract (LRT) were collected during the follow-up for microbiological examination. To evaluate the homogeneity, GM-PFGE was performed on strains responsible for VAP that had the same biochemical phenotype as those isolated from gastric juice and subglottic secretions sequentially. Among 44 VAP patients, 76 strains were isolated from LRT and considered responsible for VAP. Twenty-two isolates had the same biochemical phenotype with the corresponding gastric isolates. The homology was further confirmed using GM-PFGE in 12 episodes of VAP. Nearly 30 % of VAPs were caused by microaspiration based on the analysis of bacterial phenotype or GM-PFGE. In addition, 58.3 % patients with gastric colonization developed VAP, especially late-onset VAP (LOP). Gastropulmonary infection route exists in VAP especially LOP in elderly ventilated patients. It is one of the important mechanisms in the development of VAP.
High percentage of alpha 1-globulin in serum protein is associated with unfavorable prognosis in non-small cell lung cancer
Qu, X;Pang, ZF;Yi, WW;Wang, Y;Wang, K;Liu, Q;Du, JJ
MEDICAL ONCOLOGY 2014年 31卷10期
ALPHA-1-ANTITRYPSIN DEFICIENCY; EPITHELIAL-CELLS; CARCINOMA; INHIBITOR; ALPHA-2-MACROGLOBULIN; ELECTROPHORESIS; ADENOCARCINOMA; CLASSIFICATION; GROWTH
The association of the percentage composition of serum protein in patients undergoing lung resections for non-small cell lung cancer (NSCLC) with overall survival and recurrence-free survival has never been investigated. Patients were selected consecutively from the database of the Bio-Bank of Shandong Provincial Hospital. We retrospectively examined the impact of preoperative percentage composition of serum protein detected by serum protein electrophoresis on survival. Furthermore, we investigated the relationships between the potential prognostic biomarkers and clinicopathological factors. A total of 390 patients were evaluated. The higher percentage of alpha 1-globulin in serum protein was significantly associated with histology type (p = 0.001), worse tumor status (p = 0.001) and higher pathological stage (p = 0.004). The alpha 1-globulin percentage composition was an independent prognostic factor for overall survival (hazard ratio 1.52, 95 % CI 1.04-2.23, p = 0.03). High percentage of alpha 1-globulin in serum protein was also related to short recurrence survival (hazard ratio 1.56, 95 % CI 1.14- 2.13, p = 0.005). Our results showed that the percentage of alpha 1-globulin in serum protein may be an independent prognostic factor in NSCLC.
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