Torosian M H, Mullen J L, Miller E E, Zinsser K R, Stein T P, Buzby G P
JPEN J Parenter Enteral Nutr. 1983 Jul-Aug;7(4):337-45. doi: 10.1177/0148607183007004337.
Forced feeding has been shown to effectively stimulate tumor metabolism in numerous animal models. Significant acceleration of tumor growth by exogenous nutrient administration is generally considered to be detrimental to the host. The present study was performed to determine if substrate-induced alterations in tumor metabolism could be exploited to enhance tumor response to cycle-specific chemotherapy. Following subcutaneous mammary tumor implantation (AC-33) and protein depletion, 39 female Lewis/Wistar rats were randomly assigned to one of four nutritional regimens for 48 hr: (1) protein-depleted food (0.03% protein) ad libitum po, (2) parenteral carbohydrate (18.6% dextrose), (3) parenteral amino acids (2.8% amino acids), or (4) total parenteral nutrition (18.6% dextrose/2.8% amino acids). Methotrexate (5 mg/kg im) was administered to all animals 2 hr after initiating these nutritional regimens. Tumor volume and host toxicity were monitored throughout the study. At sacrifice, significant reduction in tumor volume was observed in animals receiving parenteral amino acids (0.37 +/- 0.24 cm3) and total parenteral nutrition (0.25 +/- 0.18 cm3) compared to the group receiving protein-depleted food po (0.70 +/- 0.22 cm3) (p less than 0.01). In this animal model, the parenteral administration of amino acids with or without the addition of hypertonic dextrose was found to effectively potentiate tumor response to methotrexate without increasing host toxicity.
在众多动物模型中，强制喂食已被证明能有效刺激肿瘤代谢。通过外源营养物质给药显著加速肿瘤生长通常被认为对宿主有害。本研究旨在确定是否可以利用底物诱导的肿瘤代谢改变来增强肿瘤对周期特异性化疗的反应。在皮下植入乳腺肿瘤（AC - 33）并使蛋白质耗竭后，39只雌性Lewis/Wistar大鼠被随机分配到四种营养方案中的一种，持续48小时：（1）随意经口给予蛋白质缺乏食物（0.03%蛋白质），（2）胃肠外给予碳水化合物（18.6%葡萄糖），（3）胃肠外给予氨基酸（2.8%氨基酸），或（4）全胃肠外营养（18.6%葡萄糖/2.8%氨基酸）。在开始这些营养方案2小时后，对所有动物给予甲氨蝶呤（5mg/kg，肌肉注射）。在整个研究过程中监测肿瘤体积和宿主毒性。处死时，与经口给予蛋白质缺乏食物的组（0.70±0.22cm³）相比，接受胃肠外氨基酸（0.37±0.24cm³）和全胃肠外营养（0.25±0.18cm³）的动物肿瘤体积显著减小（p＜0.01）。在这个动物模型中，发现胃肠外给予氨基酸，无论是否添加高渗葡萄糖，都能有效增强肿瘤对甲氨蝶呤的反应，而不增加宿主毒性。
