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作 者:曲秋莲[1] 张英鸽[1] 杨留中[1] 孙岚[1]
机构地区:[1]军事医学科学院毒物药物研究所,北京100850
出 处:《中华肿瘤杂志》2006年第4期257-260,共4页Chinese Journal of Oncology
基 金:军队"十五"规划科研基金资助项目(01Z024)
摘 要:目的探讨新型淋巴靶向制剂吸附丝裂霉素C纳米活性炭(MMC-ACNP)的抗胃癌转移和抗复发作用。方法制备MMC-ACNP并检测其毒性;建立裸鼠人胃癌腹腔种植瘤模型;将48只裸鼠分为6组:生理盐水对照组、高剂量MMC组和低剂量MMC组、高剂量MMC-ACNP组、中剂量MMC-ACNP组和低剂量MMC-ACNP组,腹腔给药。给药4周后进行血液学检查,观察裸鼠体重及肿瘤播散和生长情况。结果MMC-ACNP小鼠腹腔注射半数致死量(LD50)为46.80mg/kg,MMC小鼠腹腔注射LD50为9.33mg/kg。高剂量MMC组裸鼠体重增长缓慢,血小板显著减少,其他各组未见异常。在MMC剂量相同的情况下,MMC-ACNP的毒副作用明显低于MMC,其抑制肿瘤播散和生长的作用明显高于MMC。微小炭粒携带MMC进入肿瘤细胞核,有助于增强抑瘤效果。结论MMC-ACNP选择性高,毒副作用低,具有良好的临床应用前景。Objective To prepare a new dosage formulation of activated carbon nanoparticles adsorbing mitomycin C (MMC-ACNP) and evaluate the beneficial effects of intraperitoneally applied MMC- ACNP as a drug delivery system for lymphatic targeting in preventing metastasis and recurrence of gastric cancer. Methods MMC-ACNP was prepared. Acute toxicity after its intraperitoneal administration was evaluated. An experiment on nude mice model with transplanted human gastric cancer in 6 groups was completed to assess the effects of drugs on intra-abdominal carcinomatosis. Results The LD50 of MMC- ACNP was 46.80 mg/kg ( in terms of MMC ) while that of MMC aqueous solution was 9.33 mg/kg. The toxicity of MMC-ACNP was much less than that of the solution form. MMC-ACNP was superior to MMC aqueous solution in controlling carcinomatosis and tumor growth by intraperitoneal administration. Despite the high dose of MMC, leukopenia and thrombocytopenia were not observed in the MMC-ACNP treated group. Fine activated carbon particles adsorbing MMC entered the nuclei of tumor cells, so that the effects of the antieaneer drug were reinforced. Conclusion MMC-ACNP gives a good promise of clinical use due to its advantages such as high selectivity and low toxicity.
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