Stimulation of protein synthesis in human tumors by parenteral nutrition: evidence for modulation of tumor growth.

Abstract

The use of total parenteral nutrition (TPN) in patients with cancer has received much attention.1–3 Use of perioperative TPN in patients undergoing tumor resections and its use in patients receiving cancer chemotherapy has been examined.4 One of the early concerns regarding use of TPN in patients with cancer is the effect of administration of concentrated intravenous nutrient solutions on tumor growth rate. Although studies in animal tumor models have demonstrated preferential use of intravenous protein and energy substrates by tumors, in vivo studies in humans have failed to provide similar results. In this study, 18 nutritionally matched patients with localized rectal carcinoma were randomly divided into two groups. Both groups received a low‐residue diet and bowel preparation on days 3 and 2 before the operation. Oral intake was discontinued in both groups on day 1 before the operation. At that time, one group was given intravenous fluid (fasted group) and the other group a lipid‐based TPN regimen (fed group). Both groups received a 20‐hour infusion. Procedures for measuring the rate of tumor protein synthesis began at the end of the infusion immediately before the operation. Patients received an intravenous bolus of [13C]leucine after having blood samples drawn for determining the natural baseline concentration of the isotope in plasma proteins. Sixty to ninety minutes after injection of the isotope, patients were anesthetized and proctoscopic tumor biopsies were performed. The fractional rate of tumor protein synthesis was determined by an equation used in an earlier publication of the authors.5The investigators also performed an in vitro study using malignant colorectal cancer cells isolated from six patients who received the same TPN regimen as the fed group to rule out any contribution to protein synthesis by nontumor cells. Blood samples were taken before TPN and immediately after the 20‐hour infusion. After the malignant tumor cells were incubated in each patient's serum, protein synthetic rates were determined by measuring the incorporation of [3H]phenylalanine into cellular protein.Patients in the fed group demonstrated a significantly higher rate of tumor protein synthesis than did those patients in the fasted group (42.7 ± 3.5%/day vs 22.6 ± 1.9%/day, p =.002). Similarly, the rate of protein synthesis, expressed per gram of RNA, was also significantly increased in the group receiving TPN. The tumor RNA concentration, however, was not significantly affected by feeding. This prompted the authors to conclude that the increase in protein synthesis resulted from an increase in ribosomal synthetic activity instead of an increase in the total number of ribosomes.The measurements presented above were carried out on total tumor protein with limitations because of the heterogeneity of the tumor cell population. To confirm that it was the malignant cells that responded to the nutrient intake changes, in vitro experiments were carried out using homogeneous populations of cancer cells. The results demonstrated a significant increase in incorporation of labeled phenylalanine into protein when colorectal tumor cells were incubated with autologous serum from a patient taken after 24 hours of TPN administration compared with fasting. There was a mean increase of 81% in protein synthesis when fed patient's serum was used (p <.02) compared with serum obtained during fasting. These results provide additional evidence that exogenous nutrients can modulate human tumor growth.