A novel rat model for the study of intraosseous metastatic spine cancer

A novel rat model for the study of intraosseous metastatic spine cancer
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DOI:
10.3171/spi.2005.2.3.0303
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发表时间:
2005-03-01
影响因子:
2.8
通讯作者:
Gokaslan, ZL
Gokaslan, ZL
中科院分区:
医学2区
文献类型:
--
作者:
Mantha, A;Legnani, FG;Gokaslan, ZL

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Object.虽然转移性脊柱疾病占所有脊柱肿瘤的很大比例,但尚未报道可获得和可重复的动物模型。在这项研究中,作者描述了建立大鼠骨内脊柱肿瘤模型的技术,并提出了功能和组织学分析。将18只雌性Fischer 344大鼠随机分为两组。第1组动物接受经腹暴露并将CRL-1666乳腺癌植入L-6椎体(VB)。第2组动物进行假手术。每天使用Basso-Beattie-Bresnahan量表测试后肢功能。肿瘤植入后16天,处死动物并取出其脊柱进行组织学评估。到第15天,功能分析显示,与第2组大鼠(21分中的中位功能评分21分)相比,第1组动物(21分中的中位功能评分2分)的运动功能显著降低(p = 0.0217)。第1组的下肢轻瘫发生在手术后14至16天内。组织学分析显示肿瘤通过VB增殖并进入椎管,具有明显的溶骨性活动和脊髓压迫。对这些发现的分析证明了该模型中肿瘤生长的一致性,并验证了功能测试对轻瘫发作的实用性。这种新的大鼠模型允许临床前评价新的治疗方法对患有转移性脊柱疾病的患者。
Object. Although metastatic spinal disease constitutes a significant percentage of all spinal column tumors, an accessible and reproducible animal model has not been reported. In this study the authors describe the technique for creating an intraosseous spinal tumor model in rats and present a functional and histological analysis.Methods. Eighteen female Fischer 344 rats were randomized into two groups. Group 1 animals underwent a transabdominal exposure and implantation of CRL-1666 breast adenocarcinoma into the L-6 vertebral body (VB). Animals in Group 2 underwent a sham operation. Hindlimb function was tested daily by using the Basso-Beattie-Bresnahan scale. Sixteen days after tumor implantation, animals were killed and their spines were removed for histological assessment. Statistical analysis was performed using the Wilcoxon signed-rank test.By Day 15 functional analysis showed a significant decrease in motor function in Group 1 animals (median functional score 2 of 21) compared with Group 2 rats (median functional score 21 of 21) (p = 0.0217). The onset of paraparesis in Group 1 occurred within 14 to 16 days of surgery. Histopathological analysis showed tumor proliferation through the VB and into the spinal canal, with marked osteolytic activity and spinal cord compression.Conclusions. Analysis of these findings demonstrates the consistency of tumor growth in this model and validates the utility of functional testing for onset of paresis. This new rat model allows for the preclinical evaluation of novel therapeutic treatments for patients harboring metastatic spine disease.