ABSTRACT
Objective To evaluate the efficacy and safety of gefitinib combined with concurrent thoracic radiotherapy in the treatment of local - advanced non - small cell lung cancer with sensitive EGFR mutations. Methods From June 2015 to December 2016,fifty-six eligible patients in Chongqing Three Gorges Central Hospital were randomly assigned into two groups by one to one ratio,with 28 cases in each group.A group received treatment of gefitinib combined with concurrent thoracic radiotherapy, and B group adopted concurrent chemoradiotherapy. The toxic effects were recorded and all patients were followed up as defined by the study protocol.Primary study endpoints included:severe toxic effects,objective response rate and disease control rate,progression free survival and overall survival.Results Twenty-six patients in A group completed the study,and the severe toxic effects were as followed:interstitial pneumonia(3/26),radiation esophagitis(4/26),myelosuppression,skin rashes and gastrointestinal disruption. Twenty- eight patients in B group completed the study, and the severe toxicity included: interstitial pneumonia (4/26),radiation esophagitis(3/26),myelosuppression,skin rashes and gastrointestinal disruption.No toxicity higher than gradeⅢdeveloped in both two groups,and there were no statistically significant differences in incidence rates of interstitial pneumonia and radiation esophagitis between the two groups ( all P >0. 05 ). Moreover, there were no statistically significant differences in ORR and DCR between the two groups( ORR:61.5% vs.39.3% ,P=0.102;DCR:84. 6% vs. 71. 4% , P =0. 505 ). A group showed the benefit over B group in PFS ( 12. 45 months vs. 10.35 months,P=0.036).However,OS didn＇t reach and needed further follow-up.Conclusion The modality of gefitinib combined with concurrent thoracic radiotherapy in the treatment of local -advanced non -small cell lung cancer with sensitive EGFR mutations is safe and effective,and it yet needs further follow-up.
ABSTRACT
Objective To explore biological effects of up-regulated expression of transfected FOLR1 gene on SKOV3 cell lines following action by cisplatin(DDP).Methods Three groups of cells originated from the same SKOV3 cell line were used in this research,including the SKOV3 cell line (blank control),the cell line transfected with lentiviral pWPI plasmid (no-load control) and the cell line transfected with FOLR1 gene via lentiviral pWPI plasmid (experimental group).Next,the mRNA and protein expression of FOLR1 gene in the three groups were detected by reverse transcription (RT)-PCR and western blot,respectively.Methyl thiazolyl tetrazolium (MTT) assay was used to analysis cells growth curve and identify their sensitivity to cisplatin,and their half inhibition concentration (IC5o) values were calculated.Based on the IC50 value (3.6 μg/ml) in the experimental group,different levels of cisplatin concentration (0.5 × IC50,1 × IC50,2 × IC50,respectively) were administered to the three groups of cells,and the inhibition rates,apoptosis rates as well as apoptosis proportion of each group after 24,48,72 hours were further recorded.Finally,the residual cisplatin concentrations in the three group cells acted successively by 1 × IC50 cisplatin for 48 hours were measured by high performance liquid chromatography(HPLC).P value less than 0.05 were defined as statistically significant.Results RT-PCR and western blot detection showed that stable mRNA and protein expression of the FOLR1 gene in the experimental group while the other two groups were not.MTT assay demonstrated that higher cell growth rate,sensitivity to cisplatin(IC50 =3.6 μg/ml) and inhibition rate in the experimental group compared with those in the other two groups (P ＜ 0.05),which showed no significance in intergroup comparison(P ＞ 0.05).Flow cytometry showed apoptosis rates among three groups increased with higher cisplatin concentrations and longer action duration in dosage-time dependent manner (P ＜ 0.05),and the proportion of S phase cells increased with higher cisplatin concentration in dosage-dependent manner (P ＜ 0.05) ; for the same concentration and duration,the experimental group showed significantly different apoptosis rates and S phase cells compared with the other two groups,which demonstrated no significance in intergroup comparison (P ＞ 0.05).After action by cisplatin(3.6 μg/ml) for 48 hours,HPLC showed significantly higher residual cisplatin concentration (2.60±0.21) μg/106 cell counts in experimental group than those in no-load control group (1.49 ±0.12) μg/106 cell counts and blank control group (1.54 ± 0.11)xg/106 cell counts,respectively (P ＜0.05),and the comparison within the latter two groups showed no significance (P ＞ 0.05).Conclusion Up-regulated expression of the transfected FOLR1 gene in SKOV3 cells may be associated with higher sensitivity to cisplatin,residual cisplatin concentration and higher proportion of S phase cells,and tended to inhibit cancer cells growth and induce apoptosis.