亚砷酸注射液治疗难治性B细胞非霍奇金淋巴瘤

目的：观察亚砷酸注射液（三氧化二砷，As2O3）治疗难治性B细胞非霍奇金淋巴瘤（NHL）的有效性和安全性。方法：11例B细胞NHL患者，男性9例，女性3例，中位年龄48岁，均为复治病例。给予As2O3注射液10mg／d静脉滴注，d1～d15或d1～d21，休息2周后重复。按WHO标准评价近期疗效，观察毒副反应。结果：11例患者中，获CR2例，PR3例，有效率（CR＋PR）为45．45％。主要毒副反应有骨髓抑制、肝肾功能损害和腹胀。结论：As2O3注射液可用于治疗难治性B细胞性NHL，初步观察疗效较好，值得进一步应用和观察。

含亚砷酸方案介入治疗中晚期肝癌的疗效评价

目的评价亚砷酸联合化疗药物及超液化碘油行肝动脉化疗栓塞术（TACE）治疗中晚期肝癌的疗效和不良反应。方法中晚期肝癌共65例随机分2组,A组32例行肝动脉灌注羟基喜树碱20mg或阿霉素50mg、顺铂60mg、超液化碘油5~20ml,B组33例在上述化疗药基础上加用亚砷酸20mg。观察其疗效与不良反应。结果A组客观有效率（CR＋PR）达43.8%（14/32）,获益率（CR＋PR＋NC）达71.2%（23/32）;B组客观有效率达51.1%（17/33）,获益率为93.9%（31/33）,两组客观有效率比较无显著性差异（P〉0.05）,获益率比较有显著性差异（P〈0.05）。患者血清AFP水平,A、B组治疗前后比较有非常显著性差异,A、B组治疗后比较有显著性差异。不良反应主要为骨髓抑制、恶心呕吐、疼痛、发热,两组均无Ⅳ度不良反应,无治疗相关性死亡。结论亚砷酸联合化疗药及超液化碘油行TACE治疗中晚期肝癌有较好疗效,不良反应较小,是肝癌介入治疗用药的较佳选择,值得临床推广。

Fabrication of A Folic Acid-Modified Arsenic Trioxide Prodrug Liposome and Assessment of its Anti-Hepatocellular Carcinoma Activity

Objective To reduce the toxicity and side effects of arsenic trioxide(ATO)and provide a new approach for the treatment of primary liver cancer,a folic acid-modified calcium arsenite liposomal“target-controlled”drug delivery system(FA-LP-CaAs)was fabricated using the reverse microemulsion method.Methods A Malvern particle size analyzer and a transmission electron microscope were employed to determine the particle size,distribution,zeta potential and morphology of FA-LP-CaAs.Further,inductively coupled plasma emission spectrometry was employed to determine the drug loading capacity,entrapment efficiency,and in vitro release behavior of FA-LP-CaAs.To determine its toxicity in human hepatoma cells(HepG2)and human normal hepatocytes(LO2)and its effect on HepG2 cell cycle and apoptosis,the MTT method was used.Laser confocal and flow cytometry were also employed to determine the uptake of FA-LP-CaAs by cells.After establishing a mouse liver cancer model,the in vivo distribution of the drug included in the formulation was investigated using in vivo fluorescence.To evaluate the liver cancer targeting and anti-tumor effects of FALP-CaAs in vivo,the distribution of ATO in tissues and changes in tumor volume and body weight after liposomal administration were investigated using hematoxylin-eosin(HE)-stained tumor sections.Results The particle size,zeta potential and PDI of FA-LP-CaAs were(122.67±2.18)nm,(12.81±0.75)mV and 0.22±0.01,respectively,while its drug loading capacity was 18.49%±1.14%.In vitro experimental results revealed that FA-LP-CaAs had a strong killing effect on HepG2 cells.Further,the cell uptake capacity of this formulation was found to improve.Based on in vivo assessments,FA-LP-CaAs could significantly increase the distribution of ATO in tumor sites and inhibit tumor growth.Conclusions Herein,an FA-LP-CaAs formulation was successfully fabricated.This liposomal drug delivery system had a round appearance,uniform particle size,good polydispersity coefficient,evident“core-shell”structure,high drug loading capacity and pH response,tumor targeted drug delivery and sustained drug release.These findings support further research and the application of ATO as an anti-liver cancer prodrug and provide a new method for the treatment of liver cancer.