Ratko T A, Detrisac C J, Dinger N M, Thomas C F, Kelloff G J, Moon R C
Laboratory of Pathophysiology, IIT Research Institute, Chicago, Illinois 60616.
Cancer Res. 1989 Aug 15;49(16):4472-6.
Dietary N-(4-hydroxyphenyl)retinamide (4-HPR; 3 mmol/kg diet) and s.c. injections of the antiestrogen, tamoxifen (Tx; 10 micrograms or 20 micrograms per rat, thrice weekly) were used together as adjunct chemopreventive therapy in groups of 39-40 female, Sprague-Dawley rats that each received an i.v. injection (50 mg/kg b.w.) of the mammary gland carcinogen N-methyl-N-nitrosourea (MNU). Treatment was started immediately following the surgical excision of the first (primary) mammary carcinoma from each MNU-treated rat and was continued for 180 days. When compared to the effect of treatment with 4-HPR or Tx (30 micrograms/wk) alone, the combination treatments significantly enhanced terminal survival and reduced nonrecurrent mammary cancer incidence and multiplicity. Data showing the incidence of rats bearing the first through fifth additional cancers to appear following surgical resection of a primary lesion demonstrate that combined treatment with 4-HPR/Tx was immediately and consistently more efficacious than either agent per se in suppressing subsequent tumor appearance. This effect was apparently related to the dose of Tx. These results suggest that combined treatment with 4-HPR/Tx is superior to that of either agent alone in blocking progression of incipient neoplastic lesions at both early and later stages of the process.
在39 - 40只雌性斯普拉格 - 道利大鼠中，将膳食中的N -（4 - 羟基苯基）视黄酰胺（4 - HPR；3 mmol/kg饮食）与皮下注射抗雌激素他莫昔芬（Tx；每只大鼠10微克或20微克，每周三次）一起用作辅助化学预防疗法，每只大鼠均接受静脉注射（50 mg/kg体重）乳腺致癌物N - 甲基 - N - 亚硝基脲（MNU）。在每只经MNU处理的大鼠首次（原发性）乳腺癌手术切除后立即开始治疗，并持续180天。与单独使用4 - HPR或Tx（30微克/周）治疗的效果相比，联合治疗显著提高了终末期生存率，降低了非复发性乳腺癌的发病率和多发性。显示在原发性病变手术切除后出现第一至第五例额外癌症的大鼠发生率的数据表明，4 - HPR/Tx联合治疗在抑制后续肿瘤出现方面立即且始终比单独使用任何一种药物更有效。这种效果显然与Tx的剂量有关。这些结果表明，在肿瘤发生过程的早期和后期阶段，4 - HPR/Tx联合治疗在阻断初期肿瘤病变进展方面优于单独使用任何一种药物。
