维生素E和低浓度三尖杉酯碱对K562细胞增殖动力学作用的研究

本文应用外细胞培养、克隆形成及＾３Ｈ－ＴｄＲ掺入技术观察了低浓度三尖杉酯碱和维生素Ｅ对人白血病Ｋ５６２细胞作用的细胞增殖动力学变化。     

冬虫夏草对小鼠骨髓粒—单系祖细胞增殖的影响

4—8g/kg的冬虫夏草能明显促进小鼠骨髓粒-单系祖细胞(CFU—GM)增殖,其作用维持约4天;剂量大于10g/kg时,可抑制CFU—GM增殖。4mg/kg的三尖杉酯碱(Ha)明显抑制小鼠CFU—GM增殖;但若先用冬虫夏草(6g/kg)处理小鼠,上述剂量的Ha则可使CFU—GM产率维持于对照组水平。     

三尖杉酯类生物碱对L615及P388白血病细胞cAMP含量的影响

实验证明,三尖杉酯类生物碱对某些动物移植性白血病和实体瘤有不同程度的疗效。在治疗剂量下,三尖杉酯碱能抑制肿瘤细胞有丝分裂,降低肝、脾和肿瘤组织的核酸含量,明显抑制DNA合成。三尖杉酯碱对白血病L1210杀伤动力学研究表明,它是一个细胞周期非特异性抗肿瘤药,但对S期细胞有强烈杀伤作用,对G_0期细胞也有一定影响。临床     

半合成三尖杉酯碱的抗肿瘤作用及毒性研究

Partial synthetic harringtonine was prepared as a mixture of two diastereoisomers ——harringtonine and epiharringtonine. Experimental chemotherapeutic studies'revealed that the partial synthetic harringtonine was as active as the natural harringtonine in rodent tumors (L615, L1210, and P388 leukemia, Lewis lung carcinoma, S180 and Walker256 careinosarcoma). Toxicity studies showed that the LD₅₀ of the synthetic mixture was twice as that of natural harringtonine. The biological activity of one of the diastereoisomers epiharringtonine was shown to be less than 1% of that of the other diastereoisomer——harringtonine. Epiharringtonine given intraperitoneally did not prolong the survival time of P388 leukemia mice. However, the effect of epiharringtonine in combination with harringtonine was higher than that of harringtonine alone.     

抑制细胞外调节蛋白激酶增强Jurkat淋巴瘤细胞对三尖杉酯碱的敏感性

目的 研究细胞外调节蛋白激酶（EPK）在三尖杉酯碱（HRT）诱导Jurkat淋巴瘤细胞调亡中的作用。方法 用四甲基偶氮唑盐（MTT）法、流式细胞术和Western印迹检测法分别检测细胞增殖抑制率，细胞凋亡和磷酸化ERK蛋白的表达。结果 研究发现下调磷酸化状态的细胞外调节蛋白激酶的表达可以增强淋巴瘤细胞系Jurkat对三尖杉酯碱的敏感性。结论 ERK通路对维系Jurkat淋巴瘤生存有重要作用，该通路的抑制可以增强细胞对凋亡诱导剂的敏感性。     

定量分析两种治疗方案与危险指数对慢性髓系白血病临床缓解率的影响

目的定量分析两种治疗方案与危险指数对慢性髓系白血病(CML)临床缓解率的影响。方法按治疗方案与Sokal危险指数分别进行分组,定量分析三尖杉酯碱联合阿糖胞苷(HA)与羟基脲(Hu)二种治疗方案和病人初诊时所处的危险度对慢性期CML患者所获临床疗效的影响。结果尽管HA方案治疗初诊CML慢性期患者的近期疗效优于Hu,但它并不能延长病人的慢性期维持时间(DCP);而且病人的危险指数对完全缓解率(CR)、获CR所需时间及DCP的影响均远超出治疗方案的作用。结论HA方案不能延长病人的DCP,不宜作为初诊CML慢性期患者的一线治疗方案;按危险指数将病人作出合适分层,有利于治疗方案的合理选择及科学评价。     

硼替佐米单用或联合三尖杉酯碱体外诱导HL-60细胞凋亡实验研究

本研究探讨硼替佐米（bortezomib,Bor）单用或联合三尖杉酯碱（harringtonine,HT）对HL-60细胞凋亡的影响。以不同浓度Bor、HT处理HL-60细胞12-48小时,采用MTT比色法检测细胞增殖活性,以DNA凝胶电泳、荧光显微镜检、流式细胞术检测细胞凋亡。结果表明：10-50nmol/LBor可有效抑制HL-60细胞增殖,并诱导其凋亡。其中10nmol/L剂量处理12小时即有细胞凋亡发生,延长作用时间或增加药物剂量可使细胞凋亡率明显增加。30nmol/LHT与10nmol/LBor联合应用时,可见HL-60细胞凋亡率比两种药物单独使用时显著增加。结论：Bor对HL-60细胞具有时间和剂量依赖性的细胞凋亡诱导效应,与HT联合应用有明显的协同作用。     

三尖杉酯碱类药物在眼科应用的研究进展

对近年来三尖杉酯碱类药物在眼科的研究进行了回顾,探讨了此药在眼科的临床应用,尤其是在于光眼滤过术的应用前景。     

阿霉素、5-Fu、三尖杉酯碱及去炎松对体外培养的人视网膜色素上皮细胞的抑制

应用3H-胸腺嘧啶核苷（3H－TdR）掺入及液体闪烁测量技术，观察不同浓度的阿霉素，5-氟尿嘧啶（5－Fu）、三尖杉酯碱及去炎松对体外培养的人视网膜色素上皮细胞（RPE）增殖的抑制作用。结果；阿霉素在2～32ng／ml时，对RPE细胞抑制率为85～77.2％，ID50为12ng／ml；5－Fu在0.2～3．2μg／ml时，对RPE细胞抑制率为14．5～81．7％，ID50为0．6μg／ml；三尖杉酯碱在2．5～40ng／ml时，抑制率为18．5～94．1％，ID50为4.5ng／ml；去炎松在200～350μg／ml时对RPE细胞抑制率为37．9～53．5％，ID50为340μg／ml。结论：阿霉素、5－Fu、三尖杉酯碱及去炎松能有效地抑制RPE细胞的增殖。     

Cytotoxic effects of antiproliferative agents on human retinal glial cells in vitro

Purpose: Proliferative vitreoretinopathy (PVR) is characterizedby the formation of cellular membranes on the detached retina and also in the vitreous. Glial cellscan be found in epiretinal and subretinal membranes from eyes with PVR, proliferative diabeticretinopathy (PDR), idiopathic macular pucker, uveitis and other diseases affecting theretina. Proliferation and contraction of glial cells appears to play a role in the pathogenesisof PVR. This study is designed to inspect the effectiveness of harringtonine, as well as colchicine,daunomycin and fluorouracil, against cellular proliferation of cultured human retinal glial cellsthat might be involved in the retinal and/or vitreous proliferation. Methods: Cultures of human retinal glial cells were preparedusing the enzyme digesting method. Cells that had been in culture for 2–5 passages were usedin this study. Harringtonine (0.063 g/ml 2.0 g/ml), colchicines(0.5 g/ml 16.0 g/ml), daunomycin (0.1 g/ml 3.2 g/ml) and 5-fluorouracil(0.5 g/ml 16.0 g/ml) were added to cultures of human retinal glial cellsand the proliferation rates of the cells were measured by the MTT method. Results: Harringtonine at the dosage of 0.063 g/mlinduced suppression of cellular growth, but the changes were not statistically significant (p > 0.05).At a dosage ranging from 0.125 g/ml to 2.0 g/ml, harringtonine significantly suppressedcellular growth according to the test (p < 0.01). Likewise, other antiproliferativeagents inhibited cellular growth significantly at a dosage from 1.0 g/ml to 16.0 g/ml(colchicine), 0.2 g/ml to 3.2 g/ml (daunomycin) and 1.0 g/ml to 16.0 g/ml(5-fluorouracil), but not at 0.5 g/ml (colchicine), 0.1 g/ml (daunomycin) and0.5 g/ml (5-fluorouracil). The ID₅₀ were 0.33 g/ml (harringtonine), 3.11 g/ml (colchicine), 0.79 g/ml (daunomycin) and 5.23 g/ml (5-fluorouracil), respectively.Conclusions: Harringtonine was extremely effective ininhibiting human retinal glial cell proliferation, like other antiproliferative drugs such as colchicine,daunomycin and 5-fluorouracil. Harringtonine, therefore, may be a candidate for further studies regardingthe treatment of experimental PVR.