Electrochemotherapy to the Bone Lesion of Murine Osteosarcoma

导读：电疗是一种增强抗肿瘤药物进入肿瘤细胞的新治疗方式，在本实验中，我们观察了电疗通过细胞内转运抗肿瘤药物治疗小鼠骨肉瘤的疗效。材料与方法将切除的人骨肉瘤切成小块，植入SCID小鼠后肢骨髓，在骨内形成实体瘤。移植后通过x线摄影检查肿瘤直径，当肿瘤直径达到5mm时开始实验。采用Auerbach公式评估肿瘤体积，依次比较药物组(D)+电穿孔组(E)和不使用D和E两组肿瘤体积的变化。作为抗肿瘤药物，我们使用博来霉素（BLM）。采用生物测定法对BLM肿瘤组织浓度进行分析，并比较D+E组和D不加E组的肿瘤组织浓度。结果与讨论制备了具有骨病变的小鼠骨肉瘤模型。2个月后肿瘤直径达到5mm， x线片见占位性肿瘤呈透光膨出区。在D+E组，平均肿瘤大小依次减小两个月。但此后肿瘤逐渐生长。D组和E组均不作为对照，依次观察骨快速破坏和肿瘤生长。D+E组的肿瘤组织浓度显著高于D不含E组。我们认为电穿孔作用于BLM的高积累，是药物向骨肿瘤转运的一个平均值。6周后组织学检查发现肿瘤周围可见较厚的纤维囊。囊内可见巨噬细胞样细胞浸润。肿瘤中心可见肿瘤坏死。坏死区周围肿瘤细胞零星分布，纤维化密集。我们认为，BLM电疗对小鼠骨肉瘤模型骨损伤是一种有效的治疗方式。少

INTRODUCTIONElectrochemotherapy is a new mode of treatment to enhance the entry of anti-neoplastic agents into tumor cells, In this experiment, we observed the efficacy of electrochemotherapy through intracellular transport of the anti-neoplastic agent on the murine osteosarcoma of bone.MATERIALS AND METHODSTo produce solid murine tumors in bone, resected human osteosarcoma was cut into fine pieces, and inserted into the bone marrow of the posterior limb of SCID mouse. After transplantation, the tumor diameter was checked by X-ray photogram and the experiment was started when it reached 5 mm. Tumor volume was assessed using Auerbach's formula, The changes of tumor volume were compared sequentially among the two groups : Drug(D)+Electroporation(E) and neither D nor E.As an anti-neoplastic agent, we used bleomycin (BLM). The tumor tissue concentration of BLM was analyzed based on the bio-assay and compared among the two groups : D+E and D without E.Histology was investigated on the pseud … More ocapsules and tumor necrosis.RESULTS AND DISCUSSIONSWe made a murine osteosarcoma model which had a bone lesion. It took two months till the tumor size reached 5 mm in a dimeter, And the tumor occupying lesion was seen as a radiolucent and bulging area by the X-ray photogram. In a group : D+E, mean tumor size was lessened sequentially for two months. However, the tumor was gradually grown after that. In a group : neither D nor E as a control, rapid bone destruction and tumor growth were sequentially observed. The tumor tissue concentration in a group : D+E, was significantly higher than that of the another group : D without E.We believe that electroporation acted on an high accumulation of BLM as a mean of the drug transport to the bone tumor. Histological investigation revealed that the thick fibrouscapsule was observed around the tumor in six weeks. And there were cell infiltrations of macrophage-like cells in this capsule. Tumor necrosis was observed in the cener of the tumor. Tumor cells were sporadic surrounding the necrotic area and the fibrosis was dense in these area. We concluded that electrochemotherapy wiith BLM acted on an effective mode to the bone lesion of murine osteosarcoma model. Less