Unit Twenty Four Stimulation of Tumor Growth by Nutrition Support [4]
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trient solutions to two oral diets in Lobund rats with PA-Ⅲ prostate adenocarcinoma implants. The TPN solutions consisted of carbohydrate alone; combined carbohydrate and amino acid; or carbohydrate, amino acids, and lipid. A standard protein or protein-depleted diet was used as an oral dietary control and these animals received isovolemic parenteral fluid infusions. This study demonstrated significant acceleration of primary tumor growth and lung metastasis in animals receiving TPN or the standard oral diet compared with protein depleted controls. Combined TPN with dextrose, amino acids, and lipids stimulated tumor metastasis to the greatest degree in this model. A recent study investigated additional TPN solutions in the MAC- 33 mammary adenocarcinoma in Lewis/Wistar rats. This tumor is a spontaneously metastasizing variant of the AC-33 tumor originally induced in this rat strain with the chemical carcinogen, β-aziridinopropionamide. Control animals receiving electrolyte solution were compared with animals given TPN solutions containing glucose, long-chain triglycerides, or a combination of medium-and long-chain triglycerides. Increased primary tumor volume was observed with all TPN solutions compared with the control electrolyte solution. In contrast, lung metastases were greatest in animals receiving the TPN solution containing long-hain triglycerides. An intermediate level of lung metastases were observed in glucose-based TPN and a reduction in metastases were seen in animals receiving TPN with combined medium-chain and long-chain triglycerides. These results suggest that primary tumor growth and tumor metastasis may respond differently to nutrient administration and that various nutrients may have differential effects on the process of tumor metastasis.
Human Studies
Few clinical studies have been reported to define the effect of nutrition on tumor growth in cancer patients. Nixon et al in 1981 compared TFN with oral diets in patients with metastatic colon cancer. Although no objective stimulation of tumor growth could be determined, decreased survival was observed in patients receiving TPN. Mullen et al in 1980 performed a prospective, randomized study of 25 cancer patients with upper gastrointestinal cancers. These patients were randomized to receive either an oral diet or total parenteral nutrition for 7 to 10 days before surgery. On the day of surgery, N-glycine was parenterally infused and tumor biopsies obtained to determine fractional protein synthesis rates at the time of surgery. No change in fractional rate of tumor protein synthesis was observed between patients receiving total parenteral nutrition or the oral diet preoperatively. Baron et al in 1986 studied head and neck patients before and after receiving 7 to 10 days of TPN. In this study, head and neck tumors were aspirated before and after receiving parenteral nutrition, and tumor cells were analyzed by flow cytometry to determine cellular proliferation kinetics. An increase in the number of hyperdiploid cancer cells was seen after TPN compared with pre-TPN baseline levels. Frank et al in 1991 studied head and neck cancer patients after 7 days of TPN. Compared with values obtained before initiating TPN, increased incorporation of bromodeoxyuridine into tumor cells was seen after TPN. These studies indicate the potential to accelerate tumor cell proliferation in squamous cell cancers of the h
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