通过制备拆分剂氯化(8S,9R)-(-)-N-苄基辛可尼定,拆分了外消旋联萘酚得到其两种对映异构体,以手性联萘酚为原料分别合成了配体(R)-L和(S)-L及其相应的Eu(Ⅲ)配合物(R or S)-L-Eu(NO3)3,并测定了旋光度。分别研究了配合物(R or S)-L-Eu(N...通过制备拆分剂氯化(8S,9R)-(-)-N-苄基辛可尼定,拆分了外消旋联萘酚得到其两种对映异构体,以手性联萘酚为原料分别合成了配体(R)-L和(S)-L及其相应的Eu(Ⅲ)配合物(R or S)-L-Eu(NO3)3,并测定了旋光度。分别研究了配合物(R or S)-L-Eu(NO3)3与ct-DNA的作用方式及键合常数,发现配合物与小牛胸腺DNA(ct-DNA)存在插入作用,且(R)-L-Eu3+配合物与ct-DNA的键合能力较强。由于ct-DNA对(R)-L-Eu3+配合物荧光的增敏作用,选择(R)-L-Eu3+配合物作为ct-DNA的手性荧光探针,在最佳实验条件下,其线性范围为0.11×10-5～0.55×10-5 mol·L-1,0.55×10-5～7.8×10-5 mol·L-1,检出限为5.85×10-7 mol·L-1。展开更多
Objective:Apatinib is an oral TKI targeting VEGFR-2.Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated m BC.Oral vinorelbine also holds promise as a treatment o...Objective:Apatinib is an oral TKI targeting VEGFR-2.Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated m BC.Oral vinorelbine also holds promise as a treatment of choice in patients with m BC.This study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated m BC.In addition,we detected gene variants in ct DNA to explore the therapeutic implications.Methods:This study enrolled patients with HER2-negative m BC who were pretreated with anthracycline/taxanes.Patients were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m2 on days 1,8,and 15 of every cycle(3 weeks).The primary endpoint was PFS.The secondary endpoints were ORR,CBR,OS,and safety.Patients eligible for ct DNA detection were evaluated before and during treatment.Results:Forty patients were enrolled.The median PFS was 5.2 months(95%CI,3.4–7.0 months),and the median OS was 17.4 months(95%CI,8.0–27.0 months).The ORR was 17.1%(6/35),and the CBR was 45.7%(16/35).The most common AEs included gastrointestinal reaction,myelosuppression,and hypertension.In 20 patients,ct DNA was detected at baseline and during treatment.A significant difference was found in PFS for undetected vs.detected baseline ct DNA(13.9 months vs.3.6 months,P=0.018).Conclusions:All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2-negative m BC,with acceptable and manageable toxicity profiles.Patients with no gene variant detected and lower variant allele frequencies in ct DNA at baseline showed longer PFS.展开更多
文摘通过制备拆分剂氯化(8S,9R)-(-)-N-苄基辛可尼定,拆分了外消旋联萘酚得到其两种对映异构体,以手性联萘酚为原料分别合成了配体(R)-L和(S)-L及其相应的Eu(Ⅲ)配合物(R or S)-L-Eu(NO3)3,并测定了旋光度。分别研究了配合物(R or S)-L-Eu(NO3)3与ct-DNA的作用方式及键合常数,发现配合物与小牛胸腺DNA(ct-DNA)存在插入作用,且(R)-L-Eu3+配合物与ct-DNA的键合能力较强。由于ct-DNA对(R)-L-Eu3+配合物荧光的增敏作用,选择(R)-L-Eu3+配合物作为ct-DNA的手性荧光探针,在最佳实验条件下,其线性范围为0.11×10-5～0.55×10-5 mol·L-1,0.55×10-5～7.8×10-5 mol·L-1,检出限为5.85×10-7 mol·L-1。
基金funded by the National Natural Science Foundation of China(Grant No.81472753 and 81672634)。
文摘Objective:Apatinib is an oral TKI targeting VEGFR-2.Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated m BC.Oral vinorelbine also holds promise as a treatment of choice in patients with m BC.This study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated m BC.In addition,we detected gene variants in ct DNA to explore the therapeutic implications.Methods:This study enrolled patients with HER2-negative m BC who were pretreated with anthracycline/taxanes.Patients were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m2 on days 1,8,and 15 of every cycle(3 weeks).The primary endpoint was PFS.The secondary endpoints were ORR,CBR,OS,and safety.Patients eligible for ct DNA detection were evaluated before and during treatment.Results:Forty patients were enrolled.The median PFS was 5.2 months(95%CI,3.4–7.0 months),and the median OS was 17.4 months(95%CI,8.0–27.0 months).The ORR was 17.1%(6/35),and the CBR was 45.7%(16/35).The most common AEs included gastrointestinal reaction,myelosuppression,and hypertension.In 20 patients,ct DNA was detected at baseline and during treatment.A significant difference was found in PFS for undetected vs.detected baseline ct DNA(13.9 months vs.3.6 months,P=0.018).Conclusions:All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2-negative m BC,with acceptable and manageable toxicity profiles.Patients with no gene variant detected and lower variant allele frequencies in ct DNA at baseline showed longer PFS.
