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51.
高三尖杉酯碱存在于三尖杉属植物,2012年被美国FDA批准上市用于慢性粒细胞白血病,引起医药工作者更广泛关注。目前,在其原料药的来源途径、理化性质、抗癌活性、临床应用、作用机制等方面已积累了较大量文献,现有综述主要集中在抗癌机制及在血液病应用方面,对药物研发有重要影响的原料药来源、理化性质、质量控制、构效关系等少有梳理。本文以"homoharringtonine"、"Cephalotaxine"、"Tissue culture"、"SAR"等为中、英文主题词,查询Elsevier及cnki、vip、Wanfang等数据库,归纳整理上述内容,以期为深入开发奠定基础。 相似文献
52.
本研究旨在探讨高三尖杉酯碱(HHT)对K562细胞增殖、凋亡及BCL-2和NF-κB蛋白表达的影响。不同浓度HHT作用K562细胞后用MTT法、流式细胞仪、Western blot等方法分别检测细胞增殖、凋亡、BCL-2及NF-κB蛋白表达水平。结果表明,HHT作用48h,浓度依赖性抑制K562细胞增殖,Ic50为43.89rig/ml。HHT10ng/ml作用48h,K562细胞凋亡率明显增高;细胞周期阻滞于G0/G1期;BCL-2和NF-κB蛋白表达水平明显低于对照组(P〈0.05)。结论:HHT对K562细胞有显著的增殖抑制、细胞周期阻滞和凋亡诱导作用,抑制NF-κB和BCL-2表达可能是其抗CML的机制之一。 相似文献
53.
《Expert opinion on pharmacotherapy》2013,14(6):1029-1037
Background: The anticancer activity of the natural alkaloid homoharringtonine (HHT) was first recognized by Chinese investigators. HHT exerts its activity through inhibition of protein synthesis and promotion of apoptosis. Methods: The authors reviewed the most relevant preclinical and clinical studies involving patients with chronic myelogenous leukemia (CML) receiving therapy with either natural HHT or omacetaxine mepesuccinate (Ceflatonin, Myelostat, CGX-653), a semisynthetic subcutaneously bioavailable form of HHT presently under development for the treatment of CML. Results: Prior to the advent of the tyrosine kinase inhibitor (TKI) imatinib mesilate, controlled clinical studies established HHT as the most active therapy in CML after failure of IFN-a for patients who were not candidates for allogeneic stem cell transplantation. Preliminary results from Phase II studies suggest that omacetaxine mepesuccinate is active in patients with imatinib-resistant CML, including those carrying the T315I mutation, which renders imatinib and second-generation TKIs ineffective. Conclusion: These encouraging results have propelled the development of several Phase II/III trials both in Europe and in the US to further delineate the activity of omacetaxine mepesuccinate in patients with CML who are resistant to TKI therapy. 相似文献
54.
Hai-tao MENG Lu LI Hui LIU Ying WANG Gong-chu LI Wen-bin QIAN 《Acta pharmacologica Sinica》2009,30(11):1529-1536
Aim:
To investigate the synergistic effects of SG235-TRAIL, a novel oncolytic adenovirus expressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and homoharringtonine (HHT) in human leukemia cell lines.Methods:
The combined effect of SG235-TRAIL and HHT was assessed using a crystal violet assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, followed by combination index analysis. Cell apoptosis was measured using flow cytometry combined with fluorescein-isothiocyanate-Annexin V staining. The activation of caspase pathway and the expression of Bcl-2 family proteins, TRAIL, and E1A were examined using Western blotting.Results:
HHT synergized the cytotoxicity of SG235-TRAIL against leukemia cell lines Kasumi-1, KG-1, HL-60, and U937, concomitantly with increased apoptosis and enhanced activity of caspase-3 and -9. The combination therapy resulted in significantly lower levels of Bcl-2, Mcl-1, and Bid compared to treatment of cells with either HHT or SG235-TRAIL alone, suggesting that HHT sensitizes leukemia cells to SG235-TRAIL virus through alteration of anti-apoptotic signaling elements. Importantly, HHT combined with SG235-TRAIL did not show significant cytotoxicity to normal human mononuclear cells and mesenchymal stem cells.Conclusion:
Combining oncolytic adenovirus SG235-TRAIL and HHT synergistically enhances cytotoxicity in leukemia cells in vitro, suggesting that the combination therapy could represent a rational approach for the treatment of leukemia. 相似文献55.
用改进逆流分配法分离三尖杉酯碱和高三尖杉酯碱 总被引:3,自引:1,他引:2
李建辉 《中国医院药学杂志》1998,18(1):28-29
对三尖杉酯碱和高三尖杉酯碱混合物的分离利用经改进的逆流分配法,用经pH5缓冲液饱和的氯仿作流动相,经氯仿饱和的pH5磷酸氢二钠-枸橼酸作固定相,醋酸乙酯∶丙酮(6∶2.5)作展开剂,碱性硅胶板作薄层板,经对5批混合物进行分离,均分别获得三尖杉酯碱和高三尖杉酯碱的白色结晶。各项指标检查均符合标准。 相似文献
56.
抗白血病McAbHI30免疫脂质体的制备及其体外导向实验 总被引:2,自引:1,他引:1
以人红细胞膜脂为主要膜材,制备成功MPB高三尖杉酯碱脂质体(MPB-homoharri-ngtonine-liposomes,MPB-HH-Lip),再与鼠抗人白细胞McAb HI30共价偶联,经凝胶柱层析分离,得到McAb HI30高三尖杉酯碱脂质体(简称免疫脂质体,HI30-HH-Lip)。间接免疫荧光法检测表明,HI30-HH-Lip对人系靶细胞CEM-M3具有敏感的靶向作用,并基本上保持了McAb HI30的免疫活性。 相似文献
57.
Identification of genes responsive to apoptosis in HL-60 cells 总被引:2,自引:2,他引:0
AIM: To identify genes responsive to apoptosis in HL-60 cells treated by homoharringtonine. METHODS: cDNA microarray technology was used to detect gene expression and the result of microarrays for genes (TIEG and VDUP1) was confirmed by Northern analysis. RESULTS: Seventy-five individual mRNAs whose mass changed significantly were identified. Among these genes (25 were up-regulated and 50 were down-regulated), most are known related to oncogenes and tumor suppressor. Some genes were involved in apoptosis signaling pathways.CONCLUSION: TGFβ and TNF apoptosis signaling pathways were initiated during apoptosis in HL-60 cells.TIEG and VDUP1 play important roles in mediating apoptosis. 相似文献
58.
Lévy V Zohar S Bardin C Vekhoff A Chaoui D Rio B Legrand O Sentenac S Rousselot P Raffoux E Chast F Chevret S Marie JP 《British journal of cancer》2006,95(3):253-259
To determine the maximum-tolerated dose (MTD), dose-limiting toxicities and pharmacokinetic of semisynthetic homoharringtonine (ssHHT), given as a twice daily subcutaneous (s.c.) injections for 9 days, in patients with advanced acute leukaemia, 18 patients with advanced acute myeloid leukaemia were included in this sequential Bayesian phase I dose-finding trial. A starting dose of 0.5 mg m(-2) day(-1) was explored with subsequent dose escalations of 1, 3, 5 and 6 mg m(-2) day(-1). Myelosuppression was constant. The MTD was estimated as the dose level of 5 mg m(-2) day(-1) for 9 consecutive days by s.c. route. Dose-limiting toxicities were hyperglycaemia with hyperosmolar coma at 3 mg m(-2), and (i) one anasarque and haematemesis, (ii) one life-threatening pulmonary aspergillosis, (iii) one skin rash and (iv) one scalp pain at dose level of 5 mg m(-2) day(-1). The mean half-life of ssHHT was 11.01+/-3.4 h, the volume of distribution at steady state was 2+/-1.4 l kg(-1) and the plasma clearance was 11.6+/-10.4 l h(-1). Eleven of the 12 patients with circulating leukaemic cells had blood blast clearance, two achieved complete remission and one with blast crisis of CMML returned in chronic phase. The recommended daily dose of ssHHT on the 9-day schedule is 5 mg m(-2) day(-1). 相似文献
59.
用软琼脂集落法研究了几种正常及癌细胞对三尖杉酯碱(H)及高三尖杉酯碱(HH)的剂量反应曲线。三种瘤细胞对药物的敏感性依次为HL-60,L1210及B16。正常小鼠粒系祖细胞GM-CFC对药物较耐受。HH的活性约为H的2倍。HH对L1210细胞的杀伤具有高度的时间依赖性。直接取自一名病人的肿瘤克隆原细胞对HH的敏感性低于体外传代的细胞系。 相似文献
60.
目的:建立新的高效液相色谱法(HPLC)分离测定高三尖杉酯碱及其降解产物。方法:采用HPLC,Agilent Extend?C18色谱柱;甲醇-pH2.5的磷酸盐缓冲液-三乙胺(40∶60∶0.1)为流动相;流速为0.5 ml·min-1,检测波长:240 nm。结果:在1.04~52.20 μg·ml-1范围内,溶液的浓度与峰面积呈良好的线性关系。r=0.9999,平均回收率99.5%(n=6),RSD=1.0%,高三尖杉酯碱及其降解产物得到基线分离。结论:本方法简便、快速、准确、灵敏,适用于高三尖杉酯碱注射液的含量测定及其降解产物的检查。 相似文献