Background:Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma(ESCC).The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into t...Background:Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma(ESCC).The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects.Therefore,we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first-line treatment of advanced ESCC.Methods:In this single-arm prospective phase II trial,patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg,liposomal paclitaxel 150 mg/m2,and nedaplatin 50 mg/m2 on day 1,and apatinib 250 mg on days 1-14.The treatments were repeated every 14 days for up to 9 cycles,followed by maintenance therapy with camrelizumab and apatinib.The primary endpoint was objective response rate(ORR)according to the Response Evaluation Criteria in Solid Tumors(version 1.1).Secondary endpoints included disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and safety.Results:We enrolled 30 patients between August 7,2018 and February 23,2019.The median follow-up was 24.98 months(95%confidence interval[CI]:23.05-26.16 months).The centrally assessed ORR was 80.0%(95%CI:61.4%-92.3%),with a median duration of response of 9.77 months(range:1.54 to 24.82+months).The DCR reached 96.7%(95%CI:82.8%-99.9%).The median PFS was 6.85 months(95%CI:4.46-14.20 months),and the median OS was 19.43 months(95%CI:9.93 months–not reached).The most common grade 3-4 treatmentrelated adverse events(AEs)were leukopenia(83.3%),neutropenia(60.0%),and increased aspartate aminotransferase level(26.7%).Treatment-related serious AEs included febrile neutropenia,leukopenia,and anorexia in one patient(3.3%),and single cases of increased blood bilirubin level(3.3%)and toxic epidermal necrolysis(3.3%).No treatment-related deaths occurred.Conclusions:Camrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first-line treatment demonstrated feas展开更多
目的:观察黄芪、党参提取物对紫杉醇抑制Lewis肺癌血管生成和肿瘤转移的增强作用,为中医药抗肿瘤应用提供实验依据。方法:C57BL/6小鼠右肋处皮下接种Lewis肺癌,6h后随机分为实验组、紫杉醇组和对照组。实验组接受紫杉醇联合参芪注射液治...目的:观察黄芪、党参提取物对紫杉醇抑制Lewis肺癌血管生成和肿瘤转移的增强作用,为中医药抗肿瘤应用提供实验依据。方法:C57BL/6小鼠右肋处皮下接种Lewis肺癌,6h后随机分为实验组、紫杉醇组和对照组。实验组接受紫杉醇联合参芪注射液治疗,紫杉醇组接受同等剂量的紫杉醇治疗,对照组用等体积的生理盐水代替。观察指标:移植瘤体积,肿瘤组织内微血管度和肺脏转移瘤数量,小鼠存活时间。结果:与紫杉醇治疗相比,紫杉醇联合参芪可以明显减少移植瘤内的微血管密度(10.1±4.4 vs 16.8±7.3,P<0.05)和肺脏转移瘤个数(13.4±4.3 vs 18.4±3.9,P<0.05),明显延长小鼠的存活时间(43.3±8.4d vs 36.3±6.6d,P<0.05)。结论:黄芪、党参提取物对紫杉醇抑制肿瘤血管生成和移植肿瘤转移有一定的增强作用。展开更多
Background:On May 8,2018,the China National Medical Products Administration(NMPA)approved anlotinib,an orally administered anti-angiogenesis inhibitor,for the treatment of patients with advanced non-small cell lung ca...Background:On May 8,2018,the China National Medical Products Administration(NMPA)approved anlotinib,an orally administered anti-angiogenesis inhibitor,for the treatment of patients with advanced non-small cell lung can-cer(NSCLC)who have progressed after treatment with two or more lines of prior systemic chemotherapy.Main body of the abstract:China NMPA reviewed and inspected a regional double-blinded,placebo-controlled,Phase III trial comparing the overall survival(OS)of NSCLC patients between the anlotinib and placebo arms.A total of 437 patients were randomized(2:1)to receive either anlotinib(n=294)or placebo(n=143)once daily on a 2-week on and 1-week off schedule.Patients with epidermal growth factor receptor(EGFR)or activating anaplastic lymphoma kinase(ALK)genomic tumor aberrations should have disease progression on NMPA-approved therapy.Anlotinib is the first NMPA-approved drug for patients with advanced NSCLC who have progressed on at least two lines of prior systemic chemotherapies in China.The approval was based on a statistically and clinically significant improvement in median OS with anlotinib(9.46 months)compared with placebo[6.37 months;hazard ratio(HR])=0.70,95%confidence interval(CI)=0.55-0.89;two-sided log-rank P=0.002].The confirmed objective response rate(ORR)was 9.2%in the anlotinib arm and 0.7%in the placebo arm.The median duration of response(DoR)was 4.83 months,with a 95%CI of 3.31-6.97 months.The toxicity profile of anlotinib was consistent with that of known anti-angiogenesis inhibitors.Common adverse drug reactions(ADRs)in anlotinib-treated patients included hypertension(67.4%),hand-foot syndrome(43.9%),hemoptysis(14.0%),thyroid stimulating hormone(TSH)elevation(46.6%),and corrected QT interval(QTc)prolongation(26.2%).Short conclusion:Anlotinib demonstrated a clinically significant OS prolongation as a novel therapeutic option for advanced or metastatic NSCLC following at least two lines of chemotherapy.展开更多
【目的】为提高重组人ADAM(A Disintegrin And Metalloproteinase)15去整合素结构域蛋白(rhADAM15)的表达水平。【方法】在详尽分析rhADAM15的cDNA和GST(谷胱甘肽-S-转移酶)-ADAM15结构的基础上,选择表达宿主菌并对表达质粒进行改造。...【目的】为提高重组人ADAM(A Disintegrin And Metalloproteinase)15去整合素结构域蛋白(rhADAM15)的表达水平。【方法】在详尽分析rhADAM15的cDNA和GST(谷胱甘肽-S-转移酶)-ADAM15结构的基础上,选择表达宿主菌并对表达质粒进行改造。【结果】(1)选择能为大肠杆菌稀有密码子提供额外tRNA的Escherichia coli.Rosetta(DE3)作为宿主菌,将质粒pGEX-ADAM15转化于其中在最佳诱导表达条件下获得298mg/L融合蛋白GST-ADAM15;(2)采用PCR体外定点突变技术将目标蛋白编码区稀有密码子GGA(Gly425)替换为GGC,使融合蛋白表达水平提高9.4%;(3)通过消除凝血酶识别序列附近的Pro-Glu-Phe残基,提高凝血酶酶切效率,使rhADAM15产量提高了35.7%;(4)在GGA替换为GGC基础上切除"Pro-Glu-Phe"残基,使rhADAM15产量提高到68mg/L,比分别切除"Pro-Glu-Phe"残基、GGA替换为GGC和野生型提高了19.2%、51.1%和61.9%。【结论】这一结果表明,在充分认识目标蛋白特性的基础上定向选择表达宿主并改造表达质粒能实现外源蛋白高水平表达。展开更多
基金This study was supported by the Chinese Society of Clinical Oncology(CSCO)-Hengrui Oncology Research Fund(No.Y-HR2018-364)。
文摘Background:Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma(ESCC).The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects.Therefore,we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first-line treatment of advanced ESCC.Methods:In this single-arm prospective phase II trial,patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg,liposomal paclitaxel 150 mg/m2,and nedaplatin 50 mg/m2 on day 1,and apatinib 250 mg on days 1-14.The treatments were repeated every 14 days for up to 9 cycles,followed by maintenance therapy with camrelizumab and apatinib.The primary endpoint was objective response rate(ORR)according to the Response Evaluation Criteria in Solid Tumors(version 1.1).Secondary endpoints included disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and safety.Results:We enrolled 30 patients between August 7,2018 and February 23,2019.The median follow-up was 24.98 months(95%confidence interval[CI]:23.05-26.16 months).The centrally assessed ORR was 80.0%(95%CI:61.4%-92.3%),with a median duration of response of 9.77 months(range:1.54 to 24.82+months).The DCR reached 96.7%(95%CI:82.8%-99.9%).The median PFS was 6.85 months(95%CI:4.46-14.20 months),and the median OS was 19.43 months(95%CI:9.93 months–not reached).The most common grade 3-4 treatmentrelated adverse events(AEs)were leukopenia(83.3%),neutropenia(60.0%),and increased aspartate aminotransferase level(26.7%).Treatment-related serious AEs included febrile neutropenia,leukopenia,and anorexia in one patient(3.3%),and single cases of increased blood bilirubin level(3.3%)and toxic epidermal necrolysis(3.3%).No treatment-related deaths occurred.Conclusions:Camrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first-line treatment demonstrated feas
文摘目的:观察黄芪、党参提取物对紫杉醇抑制Lewis肺癌血管生成和肿瘤转移的增强作用,为中医药抗肿瘤应用提供实验依据。方法:C57BL/6小鼠右肋处皮下接种Lewis肺癌,6h后随机分为实验组、紫杉醇组和对照组。实验组接受紫杉醇联合参芪注射液治疗,紫杉醇组接受同等剂量的紫杉醇治疗,对照组用等体积的生理盐水代替。观察指标:移植瘤体积,肿瘤组织内微血管度和肺脏转移瘤数量,小鼠存活时间。结果:与紫杉醇治疗相比,紫杉醇联合参芪可以明显减少移植瘤内的微血管密度(10.1±4.4 vs 16.8±7.3,P<0.05)和肺脏转移瘤个数(13.4±4.3 vs 18.4±3.9,P<0.05),明显延长小鼠的存活时间(43.3±8.4d vs 36.3±6.6d,P<0.05)。结论:黄芪、党参提取物对紫杉醇抑制肿瘤血管生成和移植肿瘤转移有一定的增强作用。
基金This work was supported by the Grant from Chinese National Major Project for New Drug Innovation(Grant No.2017ZX09304015)
文摘Background:On May 8,2018,the China National Medical Products Administration(NMPA)approved anlotinib,an orally administered anti-angiogenesis inhibitor,for the treatment of patients with advanced non-small cell lung can-cer(NSCLC)who have progressed after treatment with two or more lines of prior systemic chemotherapy.Main body of the abstract:China NMPA reviewed and inspected a regional double-blinded,placebo-controlled,Phase III trial comparing the overall survival(OS)of NSCLC patients between the anlotinib and placebo arms.A total of 437 patients were randomized(2:1)to receive either anlotinib(n=294)or placebo(n=143)once daily on a 2-week on and 1-week off schedule.Patients with epidermal growth factor receptor(EGFR)or activating anaplastic lymphoma kinase(ALK)genomic tumor aberrations should have disease progression on NMPA-approved therapy.Anlotinib is the first NMPA-approved drug for patients with advanced NSCLC who have progressed on at least two lines of prior systemic chemotherapies in China.The approval was based on a statistically and clinically significant improvement in median OS with anlotinib(9.46 months)compared with placebo[6.37 months;hazard ratio(HR])=0.70,95%confidence interval(CI)=0.55-0.89;two-sided log-rank P=0.002].The confirmed objective response rate(ORR)was 9.2%in the anlotinib arm and 0.7%in the placebo arm.The median duration of response(DoR)was 4.83 months,with a 95%CI of 3.31-6.97 months.The toxicity profile of anlotinib was consistent with that of known anti-angiogenesis inhibitors.Common adverse drug reactions(ADRs)in anlotinib-treated patients included hypertension(67.4%),hand-foot syndrome(43.9%),hemoptysis(14.0%),thyroid stimulating hormone(TSH)elevation(46.6%),and corrected QT interval(QTc)prolongation(26.2%).Short conclusion:Anlotinib demonstrated a clinically significant OS prolongation as a novel therapeutic option for advanced or metastatic NSCLC following at least two lines of chemotherapy.
文摘【目的】为提高重组人ADAM(A Disintegrin And Metalloproteinase)15去整合素结构域蛋白(rhADAM15)的表达水平。【方法】在详尽分析rhADAM15的cDNA和GST(谷胱甘肽-S-转移酶)-ADAM15结构的基础上,选择表达宿主菌并对表达质粒进行改造。【结果】(1)选择能为大肠杆菌稀有密码子提供额外tRNA的Escherichia coli.Rosetta(DE3)作为宿主菌,将质粒pGEX-ADAM15转化于其中在最佳诱导表达条件下获得298mg/L融合蛋白GST-ADAM15;(2)采用PCR体外定点突变技术将目标蛋白编码区稀有密码子GGA(Gly425)替换为GGC,使融合蛋白表达水平提高9.4%;(3)通过消除凝血酶识别序列附近的Pro-Glu-Phe残基,提高凝血酶酶切效率,使rhADAM15产量提高了35.7%;(4)在GGA替换为GGC基础上切除"Pro-Glu-Phe"残基,使rhADAM15产量提高到68mg/L,比分别切除"Pro-Glu-Phe"残基、GGA替换为GGC和野生型提高了19.2%、51.1%和61.9%。【结论】这一结果表明,在充分认识目标蛋白特性的基础上定向选择表达宿主并改造表达质粒能实现外源蛋白高水平表达。
