目的观察褪黑素对尼莫司汀抑制胶质瘤U118细胞增殖的增敏效应并探讨其机制。方法褪黑素和尼莫司汀单独使用或者联合使用处理胶质瘤U118细胞,采用CCK-8实验检测细胞的活性。将细胞分为对照组、褪黑素组(0.75 mmol/L)、尼莫司汀组(100μmo...目的观察褪黑素对尼莫司汀抑制胶质瘤U118细胞增殖的增敏效应并探讨其机制。方法褪黑素和尼莫司汀单独使用或者联合使用处理胶质瘤U118细胞,采用CCK-8实验检测细胞的活性。将细胞分为对照组、褪黑素组(0.75 mmol/L)、尼莫司汀组(100μmol/L)、联合治疗组(0.75 mmol/L褪黑素联合100μmol/L尼莫司汀),采用协同实验、平板克隆实验、RT-qPCR实验、western blot实验检测褪黑素对尼莫司汀抑制胶质瘤U118细胞的增敏效应及其机制。结果与对照组比较,褪黑素、尼莫司汀单独或者协同给药对胶质瘤U118细胞均具有生长抑制作用,差异均有统计学意义(P<0.05);协同实验中,褪黑素联合尼莫司汀时,U118细胞的两药相互作用指数(coefficient of drug interaction,CDI)为0.43,提示两药有协同抑制作用;平板克隆实验中,褪黑素联合尼莫司汀后U118细胞克隆形成率明显减少,差异有统计学意义(P<0.05);RT-qPCR实验中,褪黑素联合尼莫司汀后,U118细胞中COX-2m RNA的表达明显下调,差异有统计学意义(P<0.05);Western blot实验中,褪黑素联合尼莫司汀后,U118细胞中COX-2蛋白、p-IκBα/IκBα表达明显下调,差异均有统计学意义(P<0.05)。结论褪黑素可增强尼莫司汀对胶质瘤U118细胞增殖的抑制作用。展开更多
Background Homoharringtonine （HHT） is effective in treating late stage chronic myelogenous leukaemia （CML）, but little is known about long term maintenance during complete cytogenetic response. Long term efficacy ...Background Homoharringtonine （HHT） is effective in treating late stage chronic myelogenous leukaemia （CML）, but little is known about long term maintenance during complete cytogenetic response. Long term efficacy and toxicity profiles of low dose HHT were evaluated in this study. Methods One hundred and six patients with CML received 1.5 mg/m^2 of HHT alone by continuous daily infusion for seven to nine days every four weeks. Of 79 patients in the control group, 31 were treated with interferon α （IFN-α） and 48 with hydroxycarbamide. For 17 patients who failed to achieve cytogenetic response within 12 months＇ treatment of IFN-α, HHT was administered. Quantitative RT-PCR was used to detect the BCR-ABL mRNA expression in 36 Philadelphia positive CML patients enrolled after 2007. Haematological and cytogenetic responses were evaluated in all patients at the 12th month of follow-up. Long term efficacy was assessed in a follow-up with a median time of 54 months （12 months-98 months）. Results After 12 months of therapy, cytogenetic response rate of the HHT, IFN-α and hydroxycarbamide groups were 39/106, 14/31 and 3/48, and corresponding molecular cytogenetic response rates 6/18, 3/8 and 0. Of the 17 patients who received HHT as salvage treatment, 6 achieved cytogenetic response （3 major）. At the 48 months＇ follow-up, cytogenetic response was maintained in 32/39 patients treated with HHT. Patients who had cytogenetic response in HHT group or treated with IFN-α also showed longer median chronic durations, which were 45 months （12 months-98 months） and 49 months （12 months-92 months） respectively, indicating a longer survival time. Conclusions Low dose HHT alone showed considerable short term and long term efficacy in the treatment of late stage CML. It may also be a good choice for patients who have failed imatinib, IFN-α treatment or haematopoietic stem cell transplantation or cannot afford these treatments.展开更多
文摘目的观察褪黑素对尼莫司汀抑制胶质瘤U118细胞增殖的增敏效应并探讨其机制。方法褪黑素和尼莫司汀单独使用或者联合使用处理胶质瘤U118细胞,采用CCK-8实验检测细胞的活性。将细胞分为对照组、褪黑素组(0.75 mmol/L)、尼莫司汀组(100μmol/L)、联合治疗组(0.75 mmol/L褪黑素联合100μmol/L尼莫司汀),采用协同实验、平板克隆实验、RT-qPCR实验、western blot实验检测褪黑素对尼莫司汀抑制胶质瘤U118细胞的增敏效应及其机制。结果与对照组比较,褪黑素、尼莫司汀单独或者协同给药对胶质瘤U118细胞均具有生长抑制作用,差异均有统计学意义(P<0.05);协同实验中,褪黑素联合尼莫司汀时,U118细胞的两药相互作用指数(coefficient of drug interaction,CDI)为0.43,提示两药有协同抑制作用;平板克隆实验中,褪黑素联合尼莫司汀后U118细胞克隆形成率明显减少,差异有统计学意义(P<0.05);RT-qPCR实验中,褪黑素联合尼莫司汀后,U118细胞中COX-2m RNA的表达明显下调,差异有统计学意义(P<0.05);Western blot实验中,褪黑素联合尼莫司汀后,U118细胞中COX-2蛋白、p-IκBα/IκBα表达明显下调,差异均有统计学意义(P<0.05)。结论褪黑素可增强尼莫司汀对胶质瘤U118细胞增殖的抑制作用。
文摘Background Homoharringtonine （HHT） is effective in treating late stage chronic myelogenous leukaemia （CML）, but little is known about long term maintenance during complete cytogenetic response. Long term efficacy and toxicity profiles of low dose HHT were evaluated in this study. Methods One hundred and six patients with CML received 1.5 mg/m^2 of HHT alone by continuous daily infusion for seven to nine days every four weeks. Of 79 patients in the control group, 31 were treated with interferon α （IFN-α） and 48 with hydroxycarbamide. For 17 patients who failed to achieve cytogenetic response within 12 months＇ treatment of IFN-α, HHT was administered. Quantitative RT-PCR was used to detect the BCR-ABL mRNA expression in 36 Philadelphia positive CML patients enrolled after 2007. Haematological and cytogenetic responses were evaluated in all patients at the 12th month of follow-up. Long term efficacy was assessed in a follow-up with a median time of 54 months （12 months-98 months）. Results After 12 months of therapy, cytogenetic response rate of the HHT, IFN-α and hydroxycarbamide groups were 39/106, 14/31 and 3/48, and corresponding molecular cytogenetic response rates 6/18, 3/8 and 0. Of the 17 patients who received HHT as salvage treatment, 6 achieved cytogenetic response （3 major）. At the 48 months＇ follow-up, cytogenetic response was maintained in 32/39 patients treated with HHT. Patients who had cytogenetic response in HHT group or treated with IFN-α also showed longer median chronic durations, which were 45 months （12 months-98 months） and 49 months （12 months-92 months） respectively, indicating a longer survival time. Conclusions Low dose HHT alone showed considerable short term and long term efficacy in the treatment of late stage CML. It may also be a good choice for patients who have failed imatinib, IFN-α treatment or haematopoietic stem cell transplantation or cannot afford these treatments.
