Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
BMC Neurosci. 2012 Nov 1;13:137. doi: 10.1186/1471-2202-13-137.
Spinal cord metastatic lesions affect a high number of cancer patients usually resulting in spinal cord compression syndrome. A major obstacle in the research of spinal metastatic disease is the lack of a simple reproducible animal model that mimics the natural course of the disease. In this study, we present a highly reproducible rodent model that can be used for different types of cancers while mimicking the natural course of human metastatic spinal cord compression syndrome.
All sixteen Fisher 344 rats survived the dorsal approach intraosseous implantation of CRL-1666 adenocarcinoma cells and both rats survived the sham control surgery. By Day 13 functional analysis via the modified Basso-Beattie-Bresnahan (BBB) locomotor rating scale showed significant decrease in motor function; median functional score was 3 for the tumor group (p = 0.0011). Median time to paresis was 8.7 days post-operatively. MR imaging illustrated repeated and consistent tumor formation, furthermore, onset of neurological sequale was the result of tumor formation and cord compression as confirmed by histological examination.
Analysis of these findings demonstrates a repeatable and consistent tumor growth model for cancer spinal metastases in rats. This novel rat model requires a less intricate surgical procedure, and as a result minimizes procedure time while subsequently increasing consistency. Therefore, this model allows for the preclinical evaluation of therapeutics for spinal metastases that more closely replicates physiological findings.
脊髓转移瘤影响了大量癌症患者,通常导致脊髓压迫综合征。在脊髓转移疾病的研究中,一个主要障碍是缺乏简单可重复的动物模型来模拟疾病的自然病程。在这项研究中,我们提出了一种高度可重复的啮齿动物模型,可用于不同类型的癌症,同时模拟人类转移性脊髓压迫综合征的自然病程。
所有 16 只 Fisher 344 大鼠均在背侧入路骨髓腔内植入 CRL-1666 腺癌细胞后存活,且假手术组大鼠均存活。术后第 13 天通过改良的 Basso-Beattie-Bresnahan(BBB)运动评分功能分析显示运动功能明显下降;肿瘤组的平均功能评分为 3(p=0.0011)。术后麻痹平均时间为 8.7 天。磁共振成像显示反复且一致的肿瘤形成,此外,神经并发症的发生是肿瘤形成和脊髓压迫的结果,这通过组织学检查得到了证实。
这些发现的分析表明,在大鼠中存在一种可重复且一致的癌症脊柱转移肿瘤生长模型。这种新型大鼠模型需要一种不太复杂的手术程序,从而减少手术时间,同时提高一致性。因此,该模型允许对更接近生理发现的脊柱转移治疗进行临床前评估。