Abstract
BackgroundSpinal 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.ResultsAll 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.ConclusionsAnalysis 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.
Highlights
Spinal cord metastatic lesions affect a high number of cancer patients usually resulting in spinal cord compression syndrome
Metastatic spinal cord compression is a major cause of morbidity and mortality, a key obstacle in the study of this disease is the lack of reliable, practical and reproducible animal models to allow for the exploration of new treatment methodologies
We present the methodology of intraosseous tumor implantation, study the timing of functional motor loss, and observe tumor growth patterns using magnetic resonance imaging (MRI) and histopathlogic studies
Summary
Spinal cord metastatic lesions affect a high number of cancer patients usually resulting in spinal cord compression syndrome. 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. A substantial number of cancer patients develop metastatic lesions in the spinal vertebra, and are associated with high rates of morbidity and mortality. Metastatic spinal cord compression is a major cause of morbidity and mortality, a key obstacle in the study of this disease is the lack of reliable, practical and reproducible animal models to allow for the exploration of new treatment methodologies. Better models are needed to provide more reliable predictions of novel therapeutic agents in animals, and their subsequent efficacy in humans This preliminary data is essential for the investigation of new therapeutic agents, and the translation of laboratory advances to human cancer care
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