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Objective To investigate the efficacy and safety of apatinib monotherapy as subsequent-line therapy on patients with advanced ESCC. Methods We included 56 patients with advanced ESCC who were administered with apatinib monotherapy. The initial dosage of apatinib was 500mg or 250mg daily. Clinicopathological characteristics, adverse reaction and prognosis of the patients were analyzed. The primary endpoint of this study was PFS, the secondary endpoints were ORR, DCR, OS and safety of apatinib administration. Results All the 56 patients with ESCC corresponded with the eligibility criteria and were available for the evaluation of efficacy and adverse reaction. The ORR of the 56 patients who received apatinib monotherapy was 8.9% (95%CI: 3.0%-19.6%) and DCR was 64.3% (95%CI: 50.4%-76.6%). The median PFS was 3.7 months (95%CI: 3.19-4.21) and the median OS was 6.3 months (95%CI: 3.53-9.08). The common adverse reactions were hypertension (50.0%), fatigue (41.1%), loss of appetite (35.7%), hand-foot syndrome (30.4%) and diarrhea (26.8%). Conclusion Apatinib monotherapy demonstrates potential efficacy and tolerable safety as the further-line treatment for the patients with advanced ESCC. And the conclusion should be validated in prospective clinical studies subsequently.
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Objective To study the role Erk/Slug signal pathway in the radiosensitivity of MDAMB-231 cells.Methods MDA-MB-231 cells were transfected with NF-κBp65 siRNA,PUMA siRNA and Slug siRNA respectively or treated with U0126 for 24h,then the cells were irradiated with 4 Gy γ-ray.At different time points post-irradiation,the expressions of Erk1/2,NF-κBp65,Slug and PUMA protein were detected.The cell survival rate and apoptotic index were detected by MTT and TUNEL methods.Resluts Compared with 4 Gy irradiated group,the expression of PUMA was reduced in NF-κB p65 siRNA/4 Gy group,the expressions of Slug and Erk1/2 were obviously decreased but PUMA increased in U0126/4 Gy group,the expression of Erk1/2 had no change but the expression of PUMA increased significantly in Slug siRNA/4 Gyγ group.Meanwhile,at 48h post-irradiation,for U0126/4 Gy group and Slug siRNA/4 Gy group,cells survival rates were decreased to 19.78 ±2.71 (F=11.39,P＜0.05) and 17.41 ±4.58(F=15.31,P＜0.05),cell apoptosis rates were 28.61 ±4.70 (F=9.84,P＜0.05) and 27.55±6.41(F =10.31,P ＜ 0.05),respectively.At 24 h post-irradiation,for NF-κB p65 siRNA/4 Gy group and PUMA siRNA/4 Gy group,cell survival rates approached to 85.65 ± 9.60 (F =12.31,P ＜ 0.05) and 87.53±11.50 (F=13.68,P＜0.05),and cell apoptosis rates declined to 3.28 ±0.78 (F=10.83,P ＜ 0.05) and 3.46 ± 0.84 (F =9.92,P ＜ 0.05).Conclusions The radiosensitivity of MDA-MB-231cells was relative to the induction of NF-κB up-regulated PUMA,and the radioresistance was caused by the up-regulation of Slug induced by Erk1/2,which inhibited the expression of PUMA.
