Chemotherapy with or without gefitinib in patients with advanced non-small-cell lung cancer: a meta-analysis of 6,844 patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Gefitinib is widely used in patients with advanced non-small-cell lung cancer (NSCLC), in whom chemotherapy had failed. Previous trials reported inconsistent findings regarding the efficacy of gefitinib on overall survival (OS) and progression free survival (PFS). This study was to evaluate the effects of chemotherapy plus gefitinib versus chemotherapy alone on survival of patients with NSCLC.</p><p><b>METHODS</b>We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major meetings for relevant literature. Randomized controlled trials (RCTs) comparing chemotherapy with and without gefitinib in the treatment of patients with advanced NSCLC were included in our analysis. The primary endpoints were OS and PFS.</p><p><b>RESULTS</b>Of 182 relevant studies, 12 were included in the final analysis, which consisted of 6844 patients with NSCLC. Overall, we noted that gefitinib therapy had an 8% improvement in the OS as compared to the gefitinib-free therapy, but this difference was not statistically significant (HR, 0.92; 95% CI: 0.85-1.00; P=0.051). Furthermore, gefitinib therapy had significantly longer PFS compared to gefitinib-free therapy (HR, 0.72; 95% CI 0.60-0.87, P=0.001). Patients receiving gefitinib therapy also had a more frequent objective response rate (ORR) than the control arm (OR, 2.51; 95% CI, 1.67-3.78, P < 0.001). Rashes, diarrhea, dry skin, pruritus, paronychia, and abnormal hepatic function were more frequent in the gefitinib therapy group.</p><p><b>CONCLUSIONS</b>Treatment with gefitinib had a clear effect on PFS and ORR, and it might contribute considerably to the OS. Furthermore, there was some evidence of benefit for gefitinib therapy among patients with adenocarcinoma.</p>

Effect of quercetin on heat shock protein expression in HepG2 cells determined by SILAC / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the changes of heat shock protein(HSP) expression in human hepatocellular carcinoma HepG2 cells after treated by quercetin through a proteomics strategy termed SILAC (stable isotope labeling by amino acids in cell culture)-MS (mass spectrometry).</p><p><b>METHODS</b>HepG2 cells cultured in d3-labeled DMEM medium were passaged for more than ten generations to reach an enough high labeling ratio. MTT assay was used to assess the inhibitory effect of quercetin on proliferation of HepG2 cells. In SILAC, total protein was extracted from control HepG2 cells and those treated by 50 µmol/L quercetin for 48 h, and then mixed to a 1:1 ratio. After in-gel digestion and idenfication by LC-MS/MS analysis, quantification informations of changed proteins were acquired by searching on Mascot 2.0 program (MatrixScience Ltd., London) against SWISS-PROT protein database. To ensure a high confidence level for identification, those peptides with Mascot scores below the threshold value were excluded from analysis and not included in the list of quantified proteins (P < 0.01). Protein abundance was calculated as ratios of the peak intensity of the fragment ions from the labeled versus the unlabeled peptides. RT-PCR was uesd to verify the reliability of HSPs changes by quercetin treatment from the SILAC-MS results.</p><p><b>RESULTS</b>After passaged for ten generations, the d3-labeling ratio was above 95%. MTT showed that quercetin inhibited the proliferation of HepG2 cells obviously, with a IC(50) close to 50 µmol/L, and in a dose-dependent and time-dependent manner. The MS showed that the expression of almost all heat shock family proteins was down-regulated a lot. The expression of HSP90 exposed to quercetin for 48 h was decreased to 49.3% of the normal HepG2 cells, and the expression of HSP70 was decreased to 43.6% of the normal Hep G2 cells. Quantitation information showed that the expression of HSP90α, HSP76, HSP60 and HSP27 was declined to 59.3%, 44.2%, 51.3% and 62.6%, respectively. Those results demonstrated that the quantification for changed protiens by SILAC-MS was correct.</p><p><b>CONCLUSIONS</b>Quercetin can exert a significant inhibitory effect on whole expression of heat shock proteins in HepG2 cells. We suppose this maybe one of the pathways through which quercetin plays an important anti-tumor role. SILAC-MS is a reliale technique and can be used to quantify the changes of whole protein spectrum in HepG2 cells before and after treatment with some exogeneous factors.</p>

Effect of position on oxygenation in neonates after weaning from mechanical ventilation / 中国当代儿科杂志

<p><b>OBJECTIVE</b>What is the best suitable position for neonates who were weaned from mechanical ventilation has not been identified. This study aimed to evaluate the effect of the supine and prone positions on oxygenation in neonates within 6 hrs after weaning from mechanical ventilation.</p><p><b>METHODS</b>Sixty neonates who were weaned from mechanical ventilation were randomly given prone or supine position (n=30 each). They all received oxygen inspiration and SPO2 was maintained in a normal range by adjusting the oxygen flow rate (FiO2). Blood PaO2 and PaCO2 levels were measured 1 and 6 hrs after weaning and then the alveolodouble ended arrowarterial oxygen partial pressure difference (A-aDO2), respiratory index and oxygenation index were calculated.</p><p><b>RESULTS</b>Mean FiO2 used in the prone position group was significantly lower than that in the supine position group 1 and 6 hrs after weaning (P<0.01). The value of A-aDO2 in the prone position group 1 hr (171.06+/-86.55 vs 253.62+/-71.56; P<0.01) and 6 hrs after weaning (105.85+/-78.18 vs 208.48+/-86.80; P<0.01) were significantly lower than that in the supine position group. The respiratory index in the prone position group 1 and 6 hrs after weaning (2.16+/-1.24 and 1.35+/-1.11) was also reduced compared to 3.74+/-1.68 and 3.65+/-1.28 in the supine position group (P<0.01). In contrast, PaO2 in the prone position group 1 hr (88.70+/-32.65 vs 73.43+/-17.68; P<0.01) and 6 hrs (84.10+/-13.95 vs 70.20+/-20.27; P<0.01) after weaning was significantly higher than that in the supine position group. The oxygenation index in the prone position group 1 and 6 hrs after weaning (213.49+/-88.96 and 275.23+/-108.83) increased significantly compared to 141.54+/-43.25 and 160.62+/-63.03 in the supine position (P<0.01).</p><p><b>CONCLUSIONS</b>The prone position is better than the supine position for the improvement of oxygenation within 6 hrs after weaning from mechanical ventilation in neonates.</p>