Rat Brain Tumor Models and the Statistical Evaluation of Survival Data in Experimental Neuro-Oncology

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With the growing interest in gene therapy of brain tumors, there is a major need for suitable animal models that can be used to assess the efficacy of various approaches to genetically engineer brain tumor cells. This chapter will be selective rather than comprehensive, and will focus entirely on rat brain tumor models, their utility in evaluating the efficacy of various treatment modalities, and the statistical evaluation of survival data. Two recent reviews (1,2) provide much useful information about a number of the rat brain tumor models that will be discussed here, and interested readers are referred to these for additional details relating to the tumors described by us. Murine (3,4),canine (5,6),and feline (2,7) models have been described, but these will not be discussed. The rat is one of the most widely used of experimental animals (8,9) and rat brain tumor models have been used in experimental neuro-oncology since the mid-1970s (10). Druckrey (11), Benda, Schmidek, Swenberg, and Koestner (12–16) and their associates reported that central nervous system tumors could be induced selectively and reproducibly in adult rats that had been given repeated, weekly, intravenous (iv) injections of N-methylnitrosourea (NMU). Contemporaneous with this, Druckrey (11) and Swenberg (16) reported that brain tumors also could be induced in the progeny of pregnant rats that had been given a single iv injection of N-ethyl-N-nitrosourea (ENU). These studies led to the development of a number of brain tumor models that were easily reproduced, and that did not require the topical application of a chemical carcinogen to the brain. At about the same time, Bigner et al. (6) described the development of an avian sarcoma virus-induced rat brain tumor model, which also has proven to be useful. Some general principles relating to the use of rat brain tumor models will be presented, brief descriptions of the most widely used of these tumors will be reviewed, and their respective advantages and limitations will be discussed. Xenograft models (17), based on the intracerebral transplantation of human brain tumors into immunologically deficient nude rats, will not be discussed.KeywordsBrain TumorBoron Neutron Capture TherapyHerpes Simplex Virus Thymidine KinaseCumulative Hazard FunctionExperimental Brain TumorThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.