Animal Models for Nutrition in Cancer

Abstract

167 Selection of a model is central to the design of an animal study of carcinogenesis and cancer progression or metastasis. Cancer-associated malnutrition and its dietary therapy in animals is the subject of literature which is marked by the lack of a consensus approach to the use of models and dietary design. There is no single ideal animal model and valuable insights are available from a diversity of animal models. Animal models offer a great advantage in terms of standardization of study conditions, and this is countered by the very great difficulty in extrapolation of results to humans in clinical situations. Most of the work to date has addressed nutritional effects on growth of already established tumors. Treatment by chemotherapy or other approaches has not been extensively integrated into nutritional models to date.The reader is referred to an excellent review by Birt [1], which touches upon methodologic issues, theoretical considerations and design criteria for experimental studies of nutrition and cancer. Although written with particular reference to the fat level and composition of the diet, many important considerations for all types of nutritional experimentation in the cancer area are raised, including models of carcinogenesis and transplantable tumors, and considerations for dietary design. This review focuses on a subset of literature reflecting the authors' experience with models of cancer cachexia and negative nitrogen balance, mediators of protein anabolism and catabolism, and amino acid nutrition in cancer.

Animal models of the cancer anorexia–cachexia syndrome

“…There is also significant variation in anorexia even within the same animal model: The coefficient of variation 21 days after implantation of Morris hepatoma 7777 in Buffalo rats was 35% for body weight, 25% for severity of anorexia, and 17% for tumor mass [4]. Such variation can bias data interpretation.…”

“…Each has specific characteristics (Tables 2 and 3). The Yoshida hepatoma (YAH-130) induces profound anorexia and wasting at low tumor burden [4]. Tumor doubling time is very short, a drawback of this model.…”

“…Lewis lung carcinoma (LLC) induces rapid weight loss with anorexia late in the disease (2 weeks post-implant) when tumor burden represents about 6% of total body weight [10,34]. In the Morris [4]. One week later, wasting is profound mainly from rapid massive tumor mass increase.…”

“…In this model, cachexia can occur without anorexia. The YAH-130 and MAC16 models have many differences [4]. The most obvious is that YAH-130 is highly anorexigenic, while the MAC-16 is not.…”

The silent symptom early satiety: a forerunner of distinct phenotypes of anorexia/cachexia syndromes

“…Early satiety as hallmark of a gutbrain axis phenotype of anorexia/ cachexia Evidence from animal models [9] and preliminary clinical data [10] support the hypothesis of different phenotypes of the anorexia/cachexia syndromes, having simple-to-assess leading symptoms. Such putative phenotypes encompass a distinct constellation of immunological, neurohormonal, and muscular mechanisms, conceptualized also as the muscle-liver, gut-brain, and brain-muscle axes.…”