Our specific aims will be to determine individually the efficacy of chemically structured triglycerides and xylitol as components of total parenteral nutrition to better support host tissue during cancer cachexia. During the stage of exponential tumor growth, rats will be administered complete feeding regimens, isonitrogenous and isoenergetic, with non-protein energy as either 2/3 glucose plus 1/3 long chain triglyceride, 2/3 glucose plus 1/3 chemically structured triglyceride, or 1/3 glucose, plus 1/3 xylitol and 1/3 long chain triglyceride. The efficacy of such infusions will be determined by dynamic measurements of protein and glucose metabolism. Tumor growth will be evaluated by protein synthetic rate and doubling time, while host protein status will be determined by carcass analysis, fractional synthetic rates of host tissue, and whole body leucine appearance, oxidation and net balance. In addition, changes in energy expenditure and alterations in the relative contribution of different calorie sources to energy expenditure induced by alternative energy sources will be evaluated. We will determine the effect of chemically structured triglycerides and xylitol as the principal energy component of total parenteral nutrition provided at maintenance energy levels on support of host tissue during cancer cachexia. During a similar stage of tumor growth to (1) above, rats will be administered complete feeding regimens, isonitrogenous and isoenergetic, but containing 150 rather than 240 non-protein calories/kg.day, with non-protein energy as either glucose only, 1/5 glucose plus 4/5 long chain triglyceride, 1/5 glucose plus 1/5 chemically structured triglyceride, or 1/5 glucose plus 4/5 xylitol. This amount of glucose approximates glucose appearance in mildly stressed animals receiving small amounts of amino acids only (see supporting evidence). This set of experiments will explore the effects of TPN formulas on tumor growth when energy provided is at approximately the energy expenditure and glucose is provided at the low level of the usual hepatic production rate.
Tayek, J A; Blackburn, G L; Bistrian, B R (1988) Alterations in whole body, muscle, liver, and tumor tissue protein synthesis and degradation in Novikoff hepatoma and Yoshida sarcoma tumor growth studied in vivo. Cancer Res 48:1554-8 |
Crosby, L E; Bistrian, B R; Ling, P R et al. (1988) Effects of branched chain amino acid-enriched total parenteral nutrition on amino acid utilization in rats bearing Yoshida sarcoma. Cancer Res 48:2698-702 |