Prolonged chronic phase in chronic myelogenous leukemia after homoharringtonine therapy

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.     

HPLC荧光法测定高三尖杉酯碱在大鼠体内的分布

目的研究高三尖杉酯碱注射液在大鼠体内的组织分布,为该药进行临床研究及合理应用提供依据。方法生物样品在碱性条件下通过氯仿提取,用KromasilC18柱（4.6mm×150mm,5μm）,乙腈-10mmol·L-1KH2PO4缓冲液（含0.2%三乙胺,用H3PO4调pH至2.5）（25：75）为流动相,荧光检测波长为λex280nm,λem320nm。结果绝对回收率为91.27%～102.4%,最低检测限为0.5ng·mL-1。SD大鼠单次尾静脉注射高三尖杉酯碱注射液0.5,1,2h后主要效应器官的浓度分布特点是：C骨髓〉C心,主要消除器官的浓度分布特点是C肝〉C肺〉C肾。结论本法准确,灵敏度高,可用于高三尖杉酯碱的体内过程研究。高三尖杉酯碱在骨髓中有较高浓度分布,应引起重视。     

HA方案治疗CML—CP的临床研究

目的观察HA联合化疗方案对慢性粒细胞白血病慢性期（CML-CP）的临床疗效和副作用。方法选择36例初诊CML—CP患者，化疗方案为HA联合化疗5—7d，其中高三尖杉酯碱（HHT）5mg／d，阿糖胞苷（Ara-C）200mg／d。主要观察外周血白细胞数、脾脏大小、染色体及化疗副作用。结果HA化疗方案治疗CML—CP近期血液学完全缓解率55．56％，有效率91．67％；近期观察细胞遗传学未发现变化；副作用可以耐受，但是7dHA化疗方案后骨髓抑制发生率高。结论HA化疗方案对于CML—CP近期有肯定疗效，是不能行allo—BMT或者imatinib治疗的有效治疗方法。     

低分子RNA与高三尖杉酯碱联用对白血病细胞系HL-60细胞作用的实验观察

目的:研究低分子RNA与抗白血病药物高三尖杉酯碱联用对HL-60细胞药物敏感性的影响。方法:采用细胞形态学观察、四唑盐(MTT)比色法分析细胞增殖以及应用凯氏定氮法测定细胞蛋白质的含量。结果:①0.05~50μg/ml高三尖杉酯碱对HL-60细胞增殖有抑制作用,并与时间和剂量相关。②低分子RNA与高三尖杉酯碱联用能显著降低HL-60细胞的增殖率,并进一步降低细胞内蛋白质的合成。结论:低分子RNA能提高HL-60细胞对白血病药物高三尖杉酯碱的敏感性,两者联用能有效抑制白血病细胞系HL-60细胞的增殖。     

高三尖杉酯碱和血栓通对人翼状胬肉成纤维细胞周期性变化的影响

目的：研究高三尖杉酯碱和血栓通过对培养人翼状胬肉成纤维细胞周期性变化的影响。方法：对翼状胬肉组织的的成纤维细胞进行培养并传代为第３代－５代,有入三尖杉酯碱及血栓勇分别处理２４ｈ,对照组用生理盐水,应用ＰＩＤＮＡ荧光染色及流式细胞仪检测和分析细胞周期的变化。结果：高三尖杉酯碱组和血栓通组Ｇ１群体细胞明显增多,Ｓ期明显减少,与对照组比较均有明显意义,其中高三尖杉酯碱更为明显。结论：高三尖杉酯碱和血栓通     

Responses of human bone marrow progenitor cells to fluoro-ara-AMP,homoharringtonine, and elliptinium

Summary The cytotoxicity of the investigational anticancer drugs fluoro-ara-AMP, homoharringtonine, and elliptinium on normal human granulocyte-macrophage colony-forming units in culture (GM-CFU) was investigated using a bilayer soft agar system. For each drug, the dose-dependent survival curve on a semilogarithmic plot formed a straight line. The Do were: 0.51 g/ml (fluoro-ara-AMP), 0.004 g/ml (homoharringtonine) and 0.026 g/ml (elliptinium). The in vitro toxicity of drugs on bone marrow progenitor cells did not correlate with the relative myelosuppressive potency observed in vivo.     

高三尖杉酯碱通过激活Caspase-3诱导鼻咽癌细胞凋亡

目的　了解高三尖杉酯碱 (HHT)是否可通过激活Caspase 3诱导鼻咽癌细胞CNE 2Z凋亡。方法　将细胞分为 4组 :对照组、1mg/LHHT处理组 (HHT组 ) ,以及分别用Caspase抑制剂 (z VAD fmk)和Caspase 3抑制剂 (DEVD fmk)预处理 2h后 ,再用 1mg/LHHT处理的z VAD fmk +HHT组和DEVD fmk +HHT组。采用流式细胞术及荧光染色法 ,检测 4组细胞的凋亡率 ,以比色法检测它们中Caspase 3的相对活性。结果　流式细胞术和荧光染色均发现 ,HHT组的凋亡率明显高于其它各组 (P <0 .0 1) ;Caspase 3的活性于 2h开始升高 ,8h达高峰 ,明显高于其它各组 (P <0 .0 1) ,2 4h时同其它各组的差异无显著性 (P >0 .0 5 )。结论　HHT可通过激活Cas pase 3诱导CNE 2Z细胞凋亡 ,Caspase 3的活性升高具有时间依赖性     

STI 571治疗慢性期慢性粒细胞白血病的初步结果分析

目的观察STI 571治疗慢性粒细胞白血病慢性期(CML-CP)与加速期(CML-AP)患者的疗效差异。方法19例CML患者(Ph染色体阳性率和/或荧光原位杂交(FISH)检测双标双融合bcr/abl基因阳性率均>90%)的中位年龄38岁,12例曾经干扰素-α(IFN-α)治疗失败。CML-AP 5例,CML-CP 14例,其中CML-CP早期(诊断≤1年)9例,CML-CP晚期(诊断3~6年)5例。19例患者全部服用STI 571 300~500 mg/d,其中5例CML-AP同时联用高三尖杉酯硷1~2 mg/d,7~14 d为1疗程(中位数疗程1.5个)。治疗的中位数时间4.5个月,治疗≥3个月后复查Ph染色体和FISH-bcr/abl。结果CML患者的血液学完全缓解率为100%,主要细胞遗传学反应率79%;CML-CP早期患者的细胞遗传学完全缓解率高于CML-CP晚期和CML-AP的患者(88.9% vs40.0% vs0%)。结论STI 571治疗CML的血液学完全缓解率高,细胞遗传学反应率在CML-CP早期的患者中最高。