Seabloom Donna E, Galbraith Art R, Haynes Anna M, Fujita Alisha S, Antonides Jenny D, Wuertz Beverly R, Steele Vernon E, Ondrey Frank G, Wattenberg Lee W
Masonic Cancer Center, University of MinnesotaMMC396, 420 Delaware St. SE, Minneapolis, MN 55455, America.
Department of Otolaryngology, University of MinnesotaMMC396, 420 Delaware St. SE, Minneapolis, MN 55455, America.
Am J Transl Res. 2018 Mar 15;10(3):875-880. eCollection 2018.
Talactoferrin alpha is a promising non-toxic solid tumor cancer agent that met with success in the treatment of early-stage lung cancer clinically in humans. It is well-tolerated, anddendritic cell-stimulation is a target. We tested the efficacy of this agent in a chemoprevention setting in A/J mice. All groups received benzo[a]pyrene (B[a]P) by oral gavage in three doses of 3 mg/kg body weight over the course of one week. Animals were then randomized into 5 groups of 24 mice per group based on weight. Experimental diets oftalactoferrin alpha (Agennix Inc., Indianapolis, IN), at 1.40% and 0.42% of the diet, were started one week or eight weeks after the last dose of B[a]P. Animals were continued on the feeding schedule, weighed weekly, and monitored for toxicity. The study was concluded 16 weeks after administration of B[a]P. The agent was well-tolerated for the duration of the experiment and there was no observable toxicity or weight change. The average number of adenomas per animal was 14.04 ± 0.93 (N=24) in the control group, 18.14 ± 1.45 (N=22) in the early low-dose group, 16.70 ± 1.30 (N=23) in the late low-dose group, 15.09 ± 1.41 (N=23) in the early high-dose group and 14.46 ± 1.21 (N=24) in the late high-dose group. We conclude talactoferrinalpha is well-tolerated. However, it did not inhibit carcinogenesis at a dose of 1.4% or 0.42% of the diet, which equates to human doses of 1.12 g/kg/day or 0.336 g/kg/day.
α-乳铁传递蛋白是一种很有前景的无毒实体瘤癌症治疗药物,在人类早期肺癌的临床治疗中取得了成功。它耐受性良好,以刺激树突状细胞为靶点。我们在A/J小鼠的化学预防实验中测试了这种药物的疗效。所有组在一周内通过口服灌胃给予苯并[a]芘(B[a]P),剂量为3毫克/千克体重,分三次给药。然后根据体重将动物随机分为5组,每组24只小鼠。在最后一剂B[a]P给药后一周或八周开始给予含1.40%和0.42%α-乳铁传递蛋白(Agennix公司,印第安纳波利斯,印第安纳州)的实验饮食。动物继续按照喂食计划进行,每周称重,并监测毒性。在给予B[a]P 16周后结束研究。在实验期间,该药物耐受性良好,没有观察到毒性或体重变化。对照组每只动物的腺瘤平均数量为14.04±0.93(N=24),早期低剂量组为18.14±1.45(N=22),晚期低剂量组为16.70±1.30(N=23),早期高剂量组为15.09±1.41(N=23),晚期高剂量组为14.46±1.21(N=24)。我们得出结论,α-乳铁传递蛋白耐受性良好。然而,在饮食中占1.4%或0.42%的剂量下,它并未抑制致癌作用,这相当于人类剂量为1.12克/千克/天或0.336克/千克/天。