Torosian M H, Mullen J L, Stein T P, Miller E E, Zinsser K R, Buzby G P
J Surg Res. 1985 Aug;39(2):103-13. doi: 10.1016/0022-4804(85)90167-2.
Exogenous nutrient administration has been shown to significantly stimulate tumor growth in numerous animal models. The present study was performed to determine if substrate-induced alterations in tumor metabolism could be exploited to potentiate tumor response to cycle-specific chemotherapy. Following subcutaneous mammary tumor (AC-33) implantation, 55 female Lewis/Wistar rats were randomly assigned to one of three nutritional regimens for 48 hr: (1) protein-depleted chow (0.03% protein) ad lib per os, (2) standard rat chow (22.0% protein) ad lib per os, or (3) total parenteral nutrition (TPN; 18.6% dextrose/2.8% amino acids). One-half of the animals in each group received a single dose of methotrexate (5 mg/kg im) while the remaining animals received placebo (saline) injections. At sacrifice, methotrexate-treated animals receiving TPN demonstrated a significantly smaller tumor volume (0.47 +/- 0.44 cm3) compared to animals given either protein depleted chow (1.30 +/- 0.76 cm3) or standard rat chow (1.34 +/- 0.83 cm3) (P less than 0.01). In this animal model, adjuvant TPN was found to significantly potentiate tumor response to cycle-specific chemotherapy with no detectable exacerbation of host toxicity.
在众多动物模型中，外源性营养物质的给予已被证明会显著刺激肿瘤生长。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细胞周期特异性化疗的反应。在皮下植入乳腺肿瘤（AC - 33）后，55只雌性Lewis/Wistar大鼠被随机分配到三种营养方案之一，持续48小时：（1）经口随意给予蛋白质缺乏的食物（0.03%蛋白质），（2）经口随意给予标准大鼠食物（22.0%蛋白质），或（3）全胃肠外营养（TPN；18.6%葡萄糖/2.8%氨基酸）。每组动物中有一半接受单剂量甲氨蝶呤（5 mg/kg，腹腔注射），其余动物接受安慰剂（生理盐水）注射。在处死时，接受TPN的甲氨蝶呤治疗动物的肿瘤体积（0.47±0.44 cm³）明显小于给予蛋白质缺乏食物（1.30±0.76 cm³）或标准大鼠食物（1.34±0.83 cm³）的动物（P＜0.01）。在这个动物模型中，发现辅助性TPN能显著增强肿瘤对细胞周期特异性化疗的反应，且未检测到宿主毒性的加重。
