程序性死亡受体-1(programmed death receptor-1,PD-1)和程序性死亡配体-1(programmed death ligand-1,PD-L1)是重要的免疫调节因子。PD-1与PD-L1结合可抑制T细胞的活化与增殖过程,进而介导癌细胞的免疫逃逸。研究发现PD-1/PD-L1单抗用...程序性死亡受体-1(programmed death receptor-1,PD-1)和程序性死亡配体-1(programmed death ligand-1,PD-L1)是重要的免疫调节因子。PD-1与PD-L1结合可抑制T细胞的活化与增殖过程,进而介导癌细胞的免疫逃逸。研究发现PD-1/PD-L1单抗用于术前辅助治疗可显著提高肺癌患者的客观及病理缓解率,对于靶向耐药的患者也有良好的疗效。本文对PD-1/PD-L1单抗在靶向耐药和肺癌术前辅助治疗中的最新进展进行综述,详细列出了免疫治疗能够改善肺癌患者靶向治疗耐药后临床预后的证据,表明免疫治疗在肺癌术前辅助治疗方面具有极大潜力。展开更多
Multidrug resistance （MDR） of breast cancer is a major cause of failure in chemotherapy. In the present study, a distearoylphosphatidyl ethanolamine-polyethylene glycol-pemetrexed （DSPE-PEG2000-PMT） conjugate was ...Multidrug resistance （MDR） of breast cancer is a major cause of failure in chemotherapy. In the present study, a distearoylphosphatidyl ethanolamine-polyethylene glycol-pemetrexed （DSPE-PEG2000-PMT） conjugate was synthesized from DSPE-PEG2000-NH2 and pemetrexed, and targeted sunitinib plus vinorelbine liposomes were developed by modifying DSPE-PEG20o0-PMT onto the surface of liposomes to overcome the MDR of breast cancer. The synthesized DSPE-PEG2000-PMT was confirmed to be consistent with the target product by matrix-assisted laser desorption/ionization time of flight mass spectrometry （MALDI-TOF-MS）. The concentrations of sunitinib and vinorelbine were measured simultaneously by high performance liquid chromatography （HPLC）. The analysis was performed on an ODS column at 30℃ at a wavelength of 215 nm with the mobile phase consisting of acetonitrile, 0.05 M KH2PO4 （pH 3.5） and triethylamine （35：65：0.3, v/v/v）. The limits of detection for sunitinib and vinorelbine were 25 ng/mL and 5 ng/mL, respectively, and the limits of quantification for both drugs were 0.25μg/mL. Two drugs were linearly correlated in the range of 0.5-25.0 μg/mL. For varying types of liposomes, the encapsulation efficiencies were 〉90%; the particle sizes were approximately 90 nm, and zeta potentials were slightly negative. The inhibitory effects were evaluated in the resistant breast cancer MCF-7/Adr cells. The results revealed that targeted sunitinib plus vinorelbine liposomes exhibited the strongest inhibitory effect to the resistant MCF-7/Adr cells among the varying formulations. Targeted coumarin liposomes were used as a fluorescent probe to evaluate the targeting effect to resistant breast cancer MCF-7/Adr cells. The results demonstrated that the targeted coumarin liposomes displayed the highest cellular uptake compared to non-targeted formulations. In conclusion, the targeted sunitinib plus vinorelbine liposomes represented a novel type of nano-formulations, which could accumulate in the resistant breast cancer cells, thereby inhibiting proliferation of the resistant cancer cells. Accordingly, the targeted sunitinib plus vinorelbine liposomes may provide a new strategy for circumventing the drug resistance in the resistant breast cancer.展开更多
文摘程序性死亡受体-1(programmed death receptor-1,PD-1)和程序性死亡配体-1(programmed death ligand-1,PD-L1)是重要的免疫调节因子。PD-1与PD-L1结合可抑制T细胞的活化与增殖过程,进而介导癌细胞的免疫逃逸。研究发现PD-1/PD-L1单抗用于术前辅助治疗可显著提高肺癌患者的客观及病理缓解率,对于靶向耐药的患者也有良好的疗效。本文对PD-1/PD-L1单抗在靶向耐药和肺癌术前辅助治疗中的最新进展进行综述,详细列出了免疫治疗能够改善肺癌患者靶向治疗耐药后临床预后的证据,表明免疫治疗在肺癌术前辅助治疗方面具有极大潜力。
基金Beijing Natural Science Foundation(Grant No.7131009)the National Basic Research Program of China(Grant No.973 program,2013CB932501)+1 种基金the National Natural Science Foundation of China(Grant No.81373343)the Innovation Team of Ministry of Education(Grant No.BMU20110263)
文摘Multidrug resistance （MDR） of breast cancer is a major cause of failure in chemotherapy. In the present study, a distearoylphosphatidyl ethanolamine-polyethylene glycol-pemetrexed （DSPE-PEG2000-PMT） conjugate was synthesized from DSPE-PEG2000-NH2 and pemetrexed, and targeted sunitinib plus vinorelbine liposomes were developed by modifying DSPE-PEG20o0-PMT onto the surface of liposomes to overcome the MDR of breast cancer. The synthesized DSPE-PEG2000-PMT was confirmed to be consistent with the target product by matrix-assisted laser desorption/ionization time of flight mass spectrometry （MALDI-TOF-MS）. The concentrations of sunitinib and vinorelbine were measured simultaneously by high performance liquid chromatography （HPLC）. The analysis was performed on an ODS column at 30℃ at a wavelength of 215 nm with the mobile phase consisting of acetonitrile, 0.05 M KH2PO4 （pH 3.5） and triethylamine （35：65：0.3, v/v/v）. The limits of detection for sunitinib and vinorelbine were 25 ng/mL and 5 ng/mL, respectively, and the limits of quantification for both drugs were 0.25μg/mL. Two drugs were linearly correlated in the range of 0.5-25.0 μg/mL. For varying types of liposomes, the encapsulation efficiencies were 〉90%; the particle sizes were approximately 90 nm, and zeta potentials were slightly negative. The inhibitory effects were evaluated in the resistant breast cancer MCF-7/Adr cells. The results revealed that targeted sunitinib plus vinorelbine liposomes exhibited the strongest inhibitory effect to the resistant MCF-7/Adr cells among the varying formulations. Targeted coumarin liposomes were used as a fluorescent probe to evaluate the targeting effect to resistant breast cancer MCF-7/Adr cells. The results demonstrated that the targeted coumarin liposomes displayed the highest cellular uptake compared to non-targeted formulations. In conclusion, the targeted sunitinib plus vinorelbine liposomes represented a novel type of nano-formulations, which could accumulate in the resistant breast cancer cells, thereby inhibiting proliferation of the resistant cancer cells. Accordingly, the targeted sunitinib plus vinorelbine liposomes may provide a new strategy for circumventing the drug resistance in the resistant breast cancer.
