Objective To evaluate the prognostic value of the level of serum neurone specific enolase (NSE) in patients with small cell lung cancer (SCLC). Methods We searched MEDLINE, EMbase, CBMdisc, and The Cochrane Central Register of Controlled Trials (1950 to December 2007). Studies meeting the eligibility criteria were retrieved and their bibliographies were checked for other relevant publications. The quality of included studies was evaluated by 2 reviewers independently. Meta-analyses were performed for the results of homogeneous studies using STATA 7.0 software. Results Nine studies involving 2 021 SCLC patients were included. About 66.0% of patients had high serum levels of NSE, according to the cut-off value defined by the authors. The hazard ratio (HR) of high levels of NSE for overall survival (OS) was 1.27 times of that of low levels of NSE for OS in SCLC patients (95% CI 1.19 to 1.35, P=0.281). Conclusion Patients with high levels of NSE appear to have a poorer OS compared with those with low levels of NSE, thus the level of NSE has a prognostic value in SCLC patients. Due to the potential publication bias, selection bias, and measurement bias among these studies, the conclusion should be interpreted carefully. More high-quality homogeneous studies are required to accurately evaluate the prognostic value of NSE.
Objective To evaluate diagnostic value of tumor marker — the serum neuron specific enolase (NSE) in patients with suspected small cell lung cancer with lung pathological diagnosis as the gold standard. Methods A search in The Cochrane Library, PubMed, OVID, MEDLINE, EMbase, Cancerlit, China National Knowledge Infrastructure (CNKI), and CBM, was conducted from 1966 to 2008. Hand searches and additional searches were also conducted. Criteria for inclusion were established based on validity criteria for diagnostic research published by the Cochrane Methods Group on Screening and Diagnostic Tests. Subsequently, the characteristics of the included articles were appraised and extracted. Statistical analysis was performed employing Revman 4.2 software. Heterogeneity of the included articles was tested, which was used to select the proper effect model to calculate pooled weighted sensitivity and specificity. The Summary Receiver Operating Characteristic (SROC) curve was performed and the area under the curve (AUC) was calculated. Finally, sensitivity analysis was performed. Results Six articles entered this meta-analysis: four English articles, one Japanese article and one Chinese article. The quality level of the articles was C. the studies involving 2,366 patients (579 SCLC and 1,847 NSCLC patients that were diagnosed by using the gold standard) were included. The meta-analysis reported that the heterogeneity among studies was high (P=0.005, I2=70.4%), pooled sensitivity was 0.59, 95%CI 0.55 to 0.64, and pooled specificity was 0.88, 95%CI 0.87 to 0.90. The likelihood ratio was 8.17 and 0.31, respectively. The summary ROC of the meta-disc software and the area under the curve was 0.905 0. These data suggested that NSE had a relatively high false negative rate (41%) and a relatively low false positive rate (12%). Conclusion The tumor marker NSE is has diagnostic value of small cell lung cancer, but more high quality trials are required.
Objective To explore whether microRNA-203 (miR-203) targets and regulates the Toll-like receptor 4 (TLR4)/nuclear transcription factor kappa B (NF-κB)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) to protect alveolar epithelial cells from lipopolysaccharide (LPS)-induced apoptosis and inflammation injury. Methods The alveolar epithelial A549 cells were used as the research objects and divided into: Control group (normal culture), LPS group (LPS treatment), LPS+miR-NC mimics group (LPS treatment after transfection of miR-NC mimics), LPS+ miR-203 mimics group (LPS treatment after transfection of miR-203 mimics), LPS+miR-203 mimics+pcDNA group (LPS treatment after transfection of miR-203 mimics and pcDNA), LPS+miR-203 mimics+pcDNA-TLR4 group (LPS treatment after transfection of miR-203 mimics and pcDNA-TLR4). Dual luciferase reporter gene was used to detect the targeting relationship between miR-203 and TLR4; Real-time quantitative reverse transcription-polymerase chain reaction was used to detect the relative expression levels of miR-203 and TLR4 mRNA; enzyme-linked immunosorbent assay was used to measure the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6; flow cytometry was used to detect the apoptosis rate of A549 cells; Western blot was used to detect the expression of B-cell lymphoma/leukemia-2 gene (Bcl-2) and Bcl-2 associated X protein (Bax), TLR4, NF-κB and NLRP3 proteins in A549 cells. Results There was a targeted regulation relationship between miR-203 and TLR4. Compared with the Control group, the expression of miR-203, TLR4 mRNA and protein, Bax, NF-κB, and NLRP3 proteins in A549 cells in the LPS group increased, the levels of TNF-α, IL-1β and IL-6 in the cell supernatant increased, the apoptosis rate increased, the level of Bcl-2 protein in cells decreased (P<0.05). Compared with the LPS+miR-NC mimics group, the expression of TLR4 mRNA and protein, Bax, NF-κB, and NLRP3 proteins in A549 cells in the LPS+miR-203 mimics group decreased, the levels of TNF-α, IL-1β and IL-6 in the cell supernatant decreased, the apoptosis rate decreased, the expression level of miR-203 and the level of Bcl-2 protein in cells increased (P<0.05). Compared with the LPS+miR-203 mimics+pcDNA group, the expression of miR-203, TLR4 mRNA and protein, Bax, NF-κB, and NLRP3 proteins in A549 cells in the LPS+miR-203 mimics+pcDNA-TLR4 group increased, the levels of TNF-α, IL-1β and IL-6 in the cell supernatant increased, the apoptosis rate increased, the expression level of miR-203 and the level of Bcl-2 protein in cells decreased (P<0.05). Conclusion MiR-203 can target TLR4/NF-κB/NLRP3 to protect alveolar epithelial cells from apoptosis and inflammation induced by LPS.
Objective To evaluate the diagnostic value of serum neuron specific enolase (NSE) in patients with small cell lung cancer. Methods We searched MEDLINE, EMBASE, The Cochrane Library and other databases (1966 to March 2007) to collect studies which evaluated the diagnostic value of NSE in patients with small cell lung cancer. The heterogeneity of included studies was tested by the Cochrane Collaboration’s software RevMan 4.2. The Summary Receiver Operating Characteristic (SROC) curve and meta-analyses were performed by MetaDisc. Results Fifteen studies involving 4221 patients (672 SCLC and 3549 NSCLC patients, all diagnosed by the gold standard) were included. Meta-analyses showed that the heterogeneity among studies was high (P=0.000 2, I2=66.1%), the pooled sensitivity was 0.67 (95%CI 0.64 to 0.71) and the pooled specificity was 0.91 (95%CI 0.90 to 0.92). Subgroup analyses indicated that 4 of the studies which used the reagent supplied by The Academy of Military Medical Sciences (P=0.33, I2=13.4%, AUC= 0.9672, SE=0.0393) and another 4 which used the reagent supplied by Roche (P=0.23, I2=29.9%, AUC=0.8311, SE=0.0836) had no heterogeneity. Conclusion NSE could be regarded as one of the reference tests in patients with small cell lung cancer, but more high quality trials are required.
Objective To assess the clinical efficacy and safety of paclitaxel in the first-line and second-line treatment of patients with small cell lung cancer (SCLC). Methods We searched The Cochrane Library, MEDLINE, EMBASE, CBM, CNKI, VIP and etc to collect all clinical controlled trials involving the addition of paclitaxel to chemotherapy in SCLC patients. Two reviewers evaluated the quality of included trials independently. The Cochrane Collaboration’s software RevMan 4.2.2 was used for meta-analyses. Results Nine trials involving 1675 SCLC patients were included. Five trials were randomized controlled trials, and all trails didn’t mention the blinding methods. Meta analyses indicated that the PET arm (paclitaxel+cisplatin+etoposide) had a similar response rate compared with the EP arm (etoposide+cisplatin) (OR1.35, 95%CI 0.98 to 1.85). The incidences of severe thrombocytopenia (OR 1.68, 95%CI 1.12 to 2.52) and lethal toxicity (OR 4.00, 95%CI 1.77 to 9.04) were higher in the PET arm than those in the EP arm, but the incidence of severe leukocytopenia was lower in the PET arm (OR 0.50, 95%CI 0.37 to 0.68). A total of 54 treatment-related deaths were reported. Conclusion In the first-line treatment of SCLC, the combination of paclitaxel, carboplatin and etoposide improved the progression-free survival, but the combination of paclitaxel and EP did not improve the survival and was more toxic than EP alone. Paclitaxel as the second-line treatment showed some therapeutic effect. Due to the poor quality and small sample size of included trials, more well-designed multi-center randomized controlled trials should be performed.