目的:研究重组人粒细胞集落刺激因子(recombinant human granulocyte colony-stimulating factor,rhG-CSF)对大鼠局灶性脑缺血的神经元保护作用。方法:用线栓法建立大鼠大脑中动脉缺血再灌注模型,于再灌注不同时间点对治疗组和对照组进...目的:研究重组人粒细胞集落刺激因子(recombinant human granulocyte colony-stimulating factor,rhG-CSF)对大鼠局灶性脑缺血的神经元保护作用。方法:用线栓法建立大鼠大脑中动脉缺血再灌注模型,于再灌注不同时间点对治疗组和对照组进行神经缺损评分(NSS);并用免疫组织化学方法测定神经上皮干细胞蛋白(nestin)的表达。结果:与对照组相比,rhC-CSF治疗组大鼠的神经缺损评分明显降低(P<0.05);治疗组脑梗死区周围的nestin表达较对照组增多。结论:脑缺血再灌注后,一定剂量rhG-CSF可能通过提高nestin的表达,增加神经细胞的修复,改善脑卒中的预后。展开更多
Objective： The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor（PEG rhG-CSF） is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy.However, ...Objective： The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor（PEG rhG-CSF） is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy.However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy.Methods：Eligible patients received 3-cycle chemotherapy every 3 weeks.No PEG rhG-CSF was given in the first cycle.Patients experienced grade 3 or 4 neutropenia would then enter the cycle 2 and 3.In cycle 2,patients received a single subcutaneous injection of prophylactic PEG rhG-CSF on d 3,and received half-dose subcutaneous injection in cycle 3 on d 3 and d 5,respectively.Escalating doses（30,60,100 and 200μg/kg）of PEG rhG-CSF were investigated.Results：A total of 26 patients were enrolled and received chemotherapy,in which 24 and 18 patients entered cycle 2 and cycle 3 treatment,respectively.In cycle 2,the incidence of grade 3 or 4 neutropenia for patients receiving single-dose PEG rhG-CSF of 30,60,100 and 200 μg/kg was 66.67%,33.33%,22.22% and 0,respectively,with a median duration less than 1（0–2）d.No grade 3 or higher neutropenia was noted in cycle 3 in all dose cohorts.Conclusions：The pharmacokinetic and pharmacodynamic profiles of PEG rhG-CSF used in cancer patients were similar to those reported,as well as the safety.Double half dose administration model showed better efficacy result than a single dose model in terms of grade 3 neutropenia and above.The single dose of 60 μg/kg,100 μg/kg and double half dose of 30 μg/kg were recommended to the phase Ⅱ study,hoping to find a preferable method for neutropenia treatment.展开更多
文摘目的:研究重组人粒细胞集落刺激因子(recombinant human granulocyte colony-stimulating factor,rhG-CSF)对大鼠局灶性脑缺血的神经元保护作用。方法:用线栓法建立大鼠大脑中动脉缺血再灌注模型,于再灌注不同时间点对治疗组和对照组进行神经缺损评分(NSS);并用免疫组织化学方法测定神经上皮干细胞蛋白(nestin)的表达。结果:与对照组相比,rhC-CSF治疗组大鼠的神经缺损评分明显降低(P<0.05);治疗组脑梗死区周围的nestin表达较对照组增多。结论:脑缺血再灌注后,一定剂量rhG-CSF可能通过提高nestin的表达,增加神经细胞的修复,改善脑卒中的预后。
基金supported by Hangzhou Jiuyuan Gene Engineering Co., Ltdpartly funded by the Chinese National Science and Technology Major Project on Key New Drug Creation (2012ZX09303-012)Beijing Municipal Science & Technology Commission Major Project for New Drug Innovation (Z111102071011001), China
文摘Objective： The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor（PEG rhG-CSF） is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy.However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy.Methods：Eligible patients received 3-cycle chemotherapy every 3 weeks.No PEG rhG-CSF was given in the first cycle.Patients experienced grade 3 or 4 neutropenia would then enter the cycle 2 and 3.In cycle 2,patients received a single subcutaneous injection of prophylactic PEG rhG-CSF on d 3,and received half-dose subcutaneous injection in cycle 3 on d 3 and d 5,respectively.Escalating doses（30,60,100 and 200μg/kg）of PEG rhG-CSF were investigated.Results：A total of 26 patients were enrolled and received chemotherapy,in which 24 and 18 patients entered cycle 2 and cycle 3 treatment,respectively.In cycle 2,the incidence of grade 3 or 4 neutropenia for patients receiving single-dose PEG rhG-CSF of 30,60,100 and 200 μg/kg was 66.67%,33.33%,22.22% and 0,respectively,with a median duration less than 1（0–2）d.No grade 3 or higher neutropenia was noted in cycle 3 in all dose cohorts.Conclusions：The pharmacokinetic and pharmacodynamic profiles of PEG rhG-CSF used in cancer patients were similar to those reported,as well as the safety.Double half dose administration model showed better efficacy result than a single dose model in terms of grade 3 neutropenia and above.The single dose of 60 μg/kg,100 μg/kg and double half dose of 30 μg/kg were recommended to the phase Ⅱ study,hoping to find a preferable method for neutropenia treatment.
