吸入异维甲酸(13-cis视黄酸)是一种有效的肺癌chemopreventive剂在低剂量/ J小鼠:一个试点研究。
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达尔AR、Grossi IM Houchens DP, Scovell LJ, Placke我,Imondi AR,碎石机GD, De Luca LM王D, Mulshine杰
吸入异维甲酸(13-cis视黄酸)是一种有效的肺癌chemopreventive剂在低剂量/ J小鼠:一个试点研究。
癌症研究杂志2000年8月,6 (8):3015 - 24。
- PubMed ID
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10955779 (在PubMed]
- 文摘
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在以前治疗头颈癌患者中,汇票管理异维甲酸(13-cis视黄酸)减少第二aerodigestive肿瘤的发生,包括肺肿瘤,但副作用使慢性治疗问题。我们推断,吸入异维甲酸可能提供足够的药物靶细胞的功效,同时避免系统性毒性,我们在这里进行试点研究报道。男性/ J小鼠接受单一的ip剂量的聚氨酯,一个共同的实验性肺癌致癌物质,或苯并[A]芘(BaP)或4 - (methylnitrosamino) 1 - (3-pyridyl) 1-butanone (NNK),假定的烟草烟雾的主要致癌物质。第二天,接触异维甲酸气溶胶45分钟每天为1.3,20.7,或481 microg / l被启动。2周后,鼻子上的高剂量造成严重的毒性皮肤,需要减少剂量频率每周两次。作为一项预防措施,中期剂量减少到每周三个风险敞口。每周的总剂量后沉积剂量降低频率计算是0.24,1.6,和24.9毫克/公斤,低,中,高剂量,其中16%是估计沉积在肺部。每周把肺药物剂量计算是0.01,0.07,和之前报道的1.1%无效的口服剂量urethane-treated / J小鼠。10到16周后,小鼠牺牲计算肺增生、腺瘤。致癌物质,小鼠暴露于高剂量异维甲酸显示减少肿瘤的多样性从56 - 80% (P < 0.005)。 The mid dose was associated with reductions of tumor multiplicity by 67 and 88% (P < 0.005) in BaP- and NNK-treated mice, respectively, and was tolerated until approximately 12 weeks, when both these and the high-dose mice began losing weight. The low-dose mice had nonsignificant reductions of 30% (P < 0.13) and 16% (P < 0.30) for BaP- and NNK-treated mice, respectively without any evidence of side effects. For BaP- and NNK-treated mice, numbers of hyperplastic areas directly correlated to dose level and inversely to tumor number, suggesting arrested progression. Inhaled mid-dose isotretinoin caused up-regulation of lung tissue nuclear retinoic acid receptors (RARs) relative to vehicle-exposed mice, RARalpha (3.9-fold vehicle), RARbeta (3.3-fold), and RARgamma (3.7-fold), suggesting that these receptors may be useful biomarkers of retinoid activity in this system. The encouraging results from this pilot study suggest that inhaled isotretinoin merits evaluation in people at high risk for lung cancer.