Barth R F
Department of Pathology, The Ohio State University, Columbus 43210, USA.
J Neurooncol. 1998 Jan;36(1):91-102. doi: 10.1023/a:1005805203044.
Rat brain tumor models have been widely used in experimental neuro-oncology for almost three decades. The present review, which will be selective rather than comprehensive, will focus entirely on seven rat brain tumor models and their utility in evaluating the efficacy of various therapeutic modalities. Although no currently available animal brain tumor model exactly simulates human high grade brain tumors, the rat models that are currently available have provided a wealth of information on in vitro and in vivo biochemical and biological properties of brain tumors and their in vivo responses to various therapeutic modalities. Ideally, valid brain tumor models should be derived from glial cells, grow in vitro and in vivo with predictable and reproducible growth patterns that simulate human gliomas, be weakly or non-immunogenic, and their response to therapy, or lack thereof, should resemble human brain tumors. The following tumors will be discussed. The 9L gliosarcoma, which was chemically induced in an inbred Fischer rat, has been one of the most widely used of all rat brain tumor models and has provided much useful information relating to brain tumor biology and therapy. The T9 glioma, although generally unrecognized, was and probably still is the same as the 9L. Both of these tumors can be immunogenic under the appropriate circumstances, and this must be taken into consideration when using either of them for studies of therapeutic efficacy, especially if survival is used as an endpoint. The C6 glioma, which was chemically induced in an outbred Wistar rat, has been extensively used for a variety of studies, but is not syngeneic to any inbred strain. Its potential to evoke an alloimmune response is a serious limitation, if it is being used in survival studies. The F98 and RG2 (D74) gliomas were both chemically induced tumors that appear to be either weakly or non-immunogenic. These tumors have been refractory to a variety of therapeutic modalities and their invasive pattern of growth and uniform lethality following an innoculum of as few as 10 tumor cells make them particularly attractive models to test new therapeutic modalities. The Avian Sarcoma Virus induced tumors and a continuous cell line derived from one of them, designated RT-2, have been useful for studies in which de novo tumor induction is an important requirement. These tumors, however, are immunogenic and this may limit their usefulness for survival studies. Finally, a new chemically induced tumor recently has been described, the CNS-1, and it appears to have a number of properties that should make it useful in experimental neuro-oncology. It is essential to recognize, however, the limitations of each of the models that have been described, and depending upon the nature of the study to be conducted, it is important that the appropriate model be selected.
近三十年来，大鼠脑肿瘤模型已在实验神经肿瘤学中得到广泛应用。本综述将有所侧重而非面面俱到，将完全聚焦于七种大鼠脑肿瘤模型及其在评估各种治疗方式疗效方面的效用。尽管目前没有任何一种动物脑肿瘤模型能完全模拟人类高级别脑肿瘤，但现有的大鼠模型已提供了大量关于脑肿瘤体外和体内生化及生物学特性以及它们对各种治疗方式体内反应的信息。理想情况下，有效的脑肿瘤模型应源自神经胶质细胞，在体外和体内生长，具有可预测和可重复的生长模式，模拟人类胶质瘤，免疫原性弱或无免疫原性，并且它们对治疗的反应（或无反应）应类似于人类脑肿瘤。将讨论以下肿瘤。9L胶质肉瘤是在近交系Fischer大鼠中化学诱导产生的，是所有大鼠脑肿瘤模型中使用最广泛的模型之一，已提供了许多与脑肿瘤生物学和治疗相关的有用信息。T9胶质瘤虽然通常未被认可，但过去是且可能现在仍然与9L相同。在适当情况下，这两种肿瘤都可能具有免疫原性，在将它们用于治疗效果研究时，尤其是以生存作为终点时，必须考虑到这一点。C6胶质瘤是在远交系Wistar大鼠中化学诱导产生的，已广泛用于各种研究，但与任何近交系均非同基因。如果用于生存研究，其引发同种异体免疫反应的可能性是一个严重限制。F98和RG2（D74）胶质瘤都是化学诱导的肿瘤，似乎免疫原性弱或无免疫原性。这些肿瘤对多种治疗方式均具有抗性，并且其侵袭性生长模式以及接种少至10个肿瘤细胞后一致的致死性使其成为测试新治疗方式的特别有吸引力的模型。禽肉瘤病毒诱导的肿瘤以及从中衍生出的一个连续细胞系（命名为RT - 2），对于那些从头诱导肿瘤是重要要求的研究很有用。然而，这些肿瘤具有免疫原性，这可能会限制它们在生存研究中的用途。最后，最近描述了一种新的化学诱导肿瘤CNS - 1，它似乎具有许多特性，应使其在实验神经肿瘤学中有用。然而，必须认识到已描述的每种模型的局限性，并且根据要进行的研究的性质，选择合适的模型很重要。
