【目的】以3种不同方法构建BALB/c裸鼠BEL-7402人肝癌模型,并观察BALB/c裸鼠肿瘤生长情况。【方法】将51只BALB/c裸鼠分为A、B、C 3组,每组17只。A组动物皮下注射0.2 m L BEL-7402人肝癌细胞,B组动物于肝脏原位注射0.05 mL BEL-7402人...【目的】以3种不同方法构建BALB/c裸鼠BEL-7402人肝癌模型,并观察BALB/c裸鼠肿瘤生长情况。【方法】将51只BALB/c裸鼠分为A、B、C 3组,每组17只。A组动物皮下注射0.2 m L BEL-7402人肝癌细胞,B组动物于肝脏原位注射0.05 mL BEL-7402人肝癌细胞与Matrigel Matrix的混合物,C组动物于肝脏原位接种BEL-7402人肝癌细胞瘤块组织。从接种后第2周至第5周,每周测定裸鼠体质量,且每组随机取3只动物解剖取肿瘤测量其大小和质量。第5周后,观察记录各组剩余动物(每组5只)的一般状态和存活天数。采用苏木素—伊红(HE)染色观察肿瘤组织病理学变化。【结果】A、B、C 3组实验动物成瘤率均为100%。5周后,A、B、C 3组剩余动物存活天数分别为(90.8±10.2)、(75.6±14.0)、(67.4±11.1) d。解剖所取肿瘤呈结节状,组织病理学检查可见肿瘤细胞呈一定方向排列,细胞呈梭形、多边形,异型明显,可见核分裂。【结论】本实验所采用的3种不同方法均能成功建立BALB/c裸鼠BEL-7402人肝癌模型。展开更多
A simple, rapid and sensitive LC-MS/MS method was developed to quantify erlotinib and its active metabolite, OSI-420, simultaneously in BALB/c nude mice plasma. Erlotinib, OSI-420 and propranolol （internal standard）...A simple, rapid and sensitive LC-MS/MS method was developed to quantify erlotinib and its active metabolite, OSI-420, simultaneously in BALB/c nude mice plasma. Erlotinib, OSI-420 and propranolol （internal standard） were extracted from nude mice plasma samples by liquid-liquid extraction. Separation was achieved on a reversed phase ClS column with a mobile phase of acetonitrile-water （35：65, v/v） containing 5 mM ammonium formate （pH = 3.0）. All compounds were monitored by mass spectrometry with electrospray positive ionization. The lower limit of quantification was 0.5 ng/mL for both erlotinib and OSI-420; accuracy was estimated by relative error, which was in the range from 0.07% to 8.00% for erlotinib and -2.83% to 6.67% for OSI-420; precision was validated by relative standard deviation, which was from 2.28% to 15.12% for erlotinib and from 1.96% to 11.50% for OSI-420. This method was applied to a pharmacokinetic study of BALB/c nude mice following oral administration of erlotinib at 12.5 mg/kg. A 2-compartment model was used to fit the pharmacokinetics of erlotinib and 1-compartment model for the pharmacokinetics of OSI-420. The ratio of the active metabolite to parent drug in mice was greater than previously reported in humans and probably reflects interspecies difference in the rate of conversion of erlotinib to OSI-420.展开更多
文摘【目的】以3种不同方法构建BALB/c裸鼠BEL-7402人肝癌模型,并观察BALB/c裸鼠肿瘤生长情况。【方法】将51只BALB/c裸鼠分为A、B、C 3组,每组17只。A组动物皮下注射0.2 m L BEL-7402人肝癌细胞,B组动物于肝脏原位注射0.05 mL BEL-7402人肝癌细胞与Matrigel Matrix的混合物,C组动物于肝脏原位接种BEL-7402人肝癌细胞瘤块组织。从接种后第2周至第5周,每周测定裸鼠体质量,且每组随机取3只动物解剖取肿瘤测量其大小和质量。第5周后,观察记录各组剩余动物(每组5只)的一般状态和存活天数。采用苏木素—伊红(HE)染色观察肿瘤组织病理学变化。【结果】A、B、C 3组实验动物成瘤率均为100%。5周后,A、B、C 3组剩余动物存活天数分别为(90.8±10.2)、(75.6±14.0)、(67.4±11.1) d。解剖所取肿瘤呈结节状,组织病理学检查可见肿瘤细胞呈一定方向排列,细胞呈梭形、多边形,异型明显,可见核分裂。【结论】本实验所采用的3种不同方法均能成功建立BALB/c裸鼠BEL-7402人肝癌模型。
基金National Integrity Innovational Technology Platform of New Drug and Development (Grant No. 2009ZX09301-010)Innovation Team of Ministry of Education (Grant No. BMU20110263)
文摘A simple, rapid and sensitive LC-MS/MS method was developed to quantify erlotinib and its active metabolite, OSI-420, simultaneously in BALB/c nude mice plasma. Erlotinib, OSI-420 and propranolol （internal standard） were extracted from nude mice plasma samples by liquid-liquid extraction. Separation was achieved on a reversed phase ClS column with a mobile phase of acetonitrile-water （35：65, v/v） containing 5 mM ammonium formate （pH = 3.0）. All compounds were monitored by mass spectrometry with electrospray positive ionization. The lower limit of quantification was 0.5 ng/mL for both erlotinib and OSI-420; accuracy was estimated by relative error, which was in the range from 0.07% to 8.00% for erlotinib and -2.83% to 6.67% for OSI-420; precision was validated by relative standard deviation, which was from 2.28% to 15.12% for erlotinib and from 1.96% to 11.50% for OSI-420. This method was applied to a pharmacokinetic study of BALB/c nude mice following oral administration of erlotinib at 12.5 mg/kg. A 2-compartment model was used to fit the pharmacokinetics of erlotinib and 1-compartment model for the pharmacokinetics of OSI-420. The ratio of the active metabolite to parent drug in mice was greater than previously reported in humans and probably reflects interspecies difference in the rate of conversion of erlotinib to OSI-420.
