Chemopreventive efficacy of combined retinoid and tamoxifen treatment following surgical excision of a primary mammary cancer in female rats.
Chemopreventive efficacy of combined retinoid and tamoxifen treatment following surgical excision of a primary mammary cancer in female rats.
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发表时间：
1989-08
期刊：
影响因子：
11.2
通讯作者：
T. Ratko;C. Detrisac;N. Dinger;Cathy F Thomas;G. Kelloff;R. Moon
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作者：
T. Ratko;C. Detrisac;N. Dinger;Cathy F Thomas;G. Kelloff;R. Moon
饲料N-(4-羟基苯基)维甲酰胺(4-HPR；3 mmol/kg饲料)和S.C.将抗雌激素他莫昔芬(TX；每只大鼠10微克或20微克，每周三次)注射作为辅助化学预防治疗，每组39-40只雌性SD大鼠，每组接受静脉注射。注射剂(50 mg/kg B.W.)乳腺癌致癌物N-甲基-N-亚硝脲(MNU)。在手术切除每只MNU处理的大鼠的第一个(原发)乳腺癌后，立即开始治疗，并持续180天。与单独使用4-HPR或TX(30微克/周)治疗相比，联合治疗显著提高了最终存活率，降低了未复发乳腺癌的发病率和多发性。数据显示，在手术切除原发病变后出现第一到第五种额外癌症的大鼠的发病率表明，4-HPR/TX联合治疗在抑制后续肿瘤出现方面立即和一致地比任何一种药物本身更有效。这种作用明显与TX的剂量有关。这些结果表明，在早期和晚期阶段，4-HPR/TX联合治疗在阻止早期肿瘤病变进展方面优于任何一种药物。
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.