Sterling-Levis Katy, White Les
Sydney Children's Hospital, High Street, Randwick, NSW, 2031, Australia.
In Vivo. 2003 Jul-Aug;17(4):329-42.
Pre-clinical models have an important role in cancer research. This review looks at the history as well as advantages and limitations of several animal models used in the study of pediatric brain tumors. The neoplasms of specific interest are the medulloblastoma/primitive neuroectodermal tumor category of brain tumors, because of their relevance to concurrent clinical research and practice. Given the historic poor record for direct heterotransplantation of these malignancies, both the conventional subcutaneous site and immune-privileged sites are assessed, with particular emphasis on models adapted to chemotherapeutic studies. The subcutaneous site is easiest to monitor but may be sub-optimal for therapeutic assays of brain tumors due to low engraftment rate, the absence of a blood-brain barrier equivalent and other lack of similarity to the clinical situation. The addition of a basement membrane attachment matrix (Matrigel) has been shown to enhance engraftment rate and cell yield at the subcutaneous site. In contrast, the intracerebral site, which is an area of immune-privilege, is biologically suitable for the study of brain tumors and their therapy, but there is no opportunity for sequential treatment courses or assessment of tumor growth prior to the death of the animal. An intraocular xenograft model has been shown to mimic human brain tumors in its resemblance of access to systemic agents to that via the blood-brain barrier and offers advantages over other methods for the pre-clinical study of chemotherapy in medulloblastoma/primitive neuroectodermal tumor. The intraocular site allows engraftment from very small clinical samples, is suitable for sequential treatment phases and provides easy access for monitoring of tumor progress. Chemotherapeutic agents which have been evaluated in various xenograft models, both as single agents and in combination, as well as other and novel approaches to the treatment of brain tumors are reviewed.
临床前模型在癌症研究中具有重要作用。本综述探讨了用于小儿脑肿瘤研究的几种动物模型的历史、优势和局限性。特别关注的肿瘤是髓母细胞瘤/原始神经外胚层肿瘤类别，因为它们与当前的临床研究和实践相关。鉴于这些恶性肿瘤直接异种移植的历史记录不佳，本文评估了传统的皮下部位和免疫赦免部位，尤其着重于适用于化疗研究的模型。皮下部位最易于监测，但由于植入率低、缺乏血脑屏障等效物以及与临床情况缺乏其他相似性，可能不适用于脑肿瘤的治疗分析。已证明添加基底膜附着基质（基质胶）可提高皮下部位的植入率和细胞产量。相比之下，脑内部位是免疫赦免区域，在生物学上适合脑肿瘤及其治疗的研究，但在动物死亡前没有机会进行序贯治疗疗程或评估肿瘤生长。眼内异种移植模型已被证明在获取全身药物方面类似于通过血脑屏障的情况，从而能够模拟人类脑肿瘤，并且在髓母细胞瘤/原始神经外胚层肿瘤化疗的临床前研究中比其他方法具有优势。眼内部位允许从非常小的临床样本进行植入，适用于序贯治疗阶段，并便于监测肿瘤进展。本文综述了在各种异种移植模型中作为单一药物和联合药物进行评估的化疗药物，以及治疗脑肿瘤的其他新方法。
