Local delivery of OncoGel delays paresis in rat metastatic spinal tumor model
Local delivery of OncoGel delays paresis in rat metastatic spinal tumor model
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DOI：
10.3171/spi-07/08/194
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发表时间：
2007-08-01
影响因子：
2.8
通讯作者：
Witham, Timothy F.
中科院分区：
文献类型：
--
作者：
Bagley, Carlos A.;Bookland, Markus J.;Witham, Timothy F.
目的。脊柱转移性疾病在临床上每年影响数以千计的癌症患者。局部化疗代表了治疗脊柱转移性疾病的新选择。尽管转移性脊柱疾病具有临床影响，但文献目前缺乏准确的动物模型来在脊柱内有效给药局部化疗药物。方法。本研究使用雌性 Fischer 344 大鼠，每只体重 150 至 200 克。麻醉诱导后，对 L-6 腹侧椎体进行经腹入路。钻一个小孔，立即注射5μL ReGel（空白聚合物）、OncoGel（紫杉醇和ReGel）1.5%、OncoGel 3.0%或OncoGel 6.0%以确定药物毒性。基于这些结果，通过在 CRL-1666 乳腺癌转移性脊柱肿瘤模型中第 6 天瘤内注射 5 μL ReGel、OncoGel 3.0% 和 OncoGel 6.0% 进行疗效研究。使用 Basso-Beattie-Bresnahan 评分量表在术前和术后测试后肢功能。当动物死亡或被处死时，对脊髓和脊柱进行组织学分析。结果。没有观察到与所研究的任何药物相关的毒性迹象。与对照组（仅肿瘤）相比，空白聚合物组没有看到增加的益处。 OncoGel 3.0% 和 OncoGel 6.0% 在各自的研究组中可有效延迟麻痹的发作。结论。这些发现证明了 OncoGel 在转移性脊柱肿瘤次全切除病例中的潜在益处。 OncoGel 6.0% 是最有效的药物浓度，在此实验模型中提供了最佳的治疗选择。这些结果为开发治疗脊柱转移瘤的局部化疗方法提供了希望。
Object. Spinal column metastatic disease clinically affects thousands of cancer patients every year. Local chemotherapy represents a new option in the treatment of metastatic disease of the spine. Despite the clinical impact of metastatic spine disease, the literature currently lacks an accurate animal model for the effective dosing of local chemotherapeutic agents within the vertebral column.Methods. Female Fischer 344 rats, weighing 150 to 200 g each, were used in this study. After induction of anesthesia, a transabdominal approach to the ventral vertebral body of L-6 was performed. A small hole was drilled and 5 mu L of ReGel (blank polymer), OncoGel (paclitaxel and ReGel) 1.5%, OncoGel 3.0%, or OncoGel 6.0% were immediately injected to determine drug toxicity. Based on these results, efficacy studies were performed by intratumoral injection of 5 mu L of ReGel, OncoGel 3.0%, and OncoGel 6.0% on Day 6 in a CRL-1666 breast adenocarcinoma metastatic spine tumor model. Hind limb function was tested pre- and postoperatively using the Basso-Beattie-Bresnahan rating scale. Histological analysis of the spinal cord and vertebral column was performed when the animal died or was killed.Results. There were no signs of toxicity observed in association with any of the agents under study. No increased benefit was seen in the blank polymer group compared with the control group (tumor only). OncoGel 3.0% and OncoGel 6.0% were effective in delaying the onset of paralysis in the respective study groups.Conclusions. These findings demonstrate the potential benefit of OncoGel in cases of subtotal resections of metastatic spinal column tumors. OncoGel 6.0% is the most efficacious drug concentration and offers the best therapeutic option in this experimental model. These results provide promise for the development of local chemotherapeutic means to treat spinal metastases.