Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopaedic Institute, Bologna, Italy.
Clin Exp Metastasis. 2013 Dec;30(8):1033-45. doi: 10.1007/s10585-013-9601-x. Epub 2013 Jul 7.
Bone metastases impair general health status, quality of life and survival of patients. Electrochemotherapy (ECT), which combines electroporation (EP) and the administration of anticancer drugs, has been recently introduced into clinical practice for the local treatment of solid tumours. In the present study, the ability of EP with bleomycin (Bleo) to induce MRMT-1 rat breast cancer cell death was investigated in vitro. Then, an in vivo model for bone metastases was set up by the inoculation of MRMT-1 cells in rat proximal tibia. 7 days after tumour induction the animals were treated with Bleo, EP, Bleo followed by EP (ECT), or left untreated. ECT eliminated the tumour in 6 out of 8 (75 %) treated metastases. Radiological evaluation showed that the Honore score in ECT-treated animals was significantly lower when compared with the other groups (p < 0.0005) and not significantly different from healthy controls. Bone morphology in ECT-treated animals, evaluated by histological and microtomographical analyses, showed intact cortical and trabecular bone structure with new bone apposition. Histomorphometric evaluation showed that ECT-treated metastases had significantly higher bone volume, trabecular number, trabecular thickness and bone mineral density compared with those of untreated metastases (respectively p < 0.0005 for BV/TV, Tb.N and BMD; p < 0.05 for Tb.Th) or metastases treated with Bleo (p < 0.05 for BV/TV, Tb.N, p < 0.005 for BMD) or EP (p < 0.005 for BV/TV, Tb.N; p < 0.0005 for BMD). These findings suggest that early ECT treatment of bone metastases is minimally invasive, safe and effective, thus providing pre-clinical evidence for its use in the treatment of human bone metastases.
骨转移会损害患者的整体健康状况、生活质量和生存率。电化疗(ECT)结合电穿孔(EP)和抗癌药物的给药,最近已被引入临床实践,用于实体瘤的局部治疗。在本研究中,研究了 EP 联合博来霉素(Bleo)诱导 MRMT-1 大鼠乳腺癌细胞死亡的能力。然后,通过将 MRMT-1 细胞接种到大鼠胫骨近端建立了骨转移的体内模型。肿瘤诱导后 7 天,用 Bleo、EP、Bleo 后 EP(ECT)或未治疗对动物进行治疗。ECT 消除了 8 只(75%)治疗转移瘤中的 6 只。放射学评估表明,ECT 治疗组动物的 Honore 评分明显低于其他组(p<0.0005),与健康对照组无显著差异。ECT 治疗动物的骨形态学通过组织学和微断层分析进行评估,显示完整的皮质骨和小梁骨结构,有新骨形成。组织形态计量学评估表明,ECT 治疗的转移瘤与未治疗的转移瘤(BV/TV、Tb.N 和 BMD 分别为 p<0.0005;Tb.Th 为 p<0.05)或用 Bleo(BV/TV、Tb.N 和 BMD 分别为 p<0.05)或 EP(BV/TV、Tb.N 分别为 p<0.05;BMD 为 p<0.005)治疗的转移瘤相比,具有更高的骨体积、小梁数量、小梁厚度和骨密度。这些发现表明,早期 ECT 治疗骨转移是微创、安全和有效的,为其在人类骨转移治疗中的应用提供了临床前证据。