title: Enhanced tumor response to cycle-specific chemotherapy by pulse total parenteral nutrition.
abstract: 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.
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D001823:Body Composition; D001835:Body Weight; D002149:Energy Intake; D005260:Female; D007958:Leukocyte Count; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D009584:Nitrogen / Q000378:metabolism; D010288:Parenteral Nutrition; D010289:Parenteral Nutrition, Total; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D009584:Nitrogen; D008727:Methotrexate