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骨水泥中的镉诱导骨肉瘤细胞坏死并降低其活力:异种移植研究。

Cadmium in bone cement induces necrosis and decreases the viability of residual osteosarcoma cells: A xenograft study.

机构信息

Department of Orthopedics, Kütahya University of Health Sciences University, School of Medicine, Kütahya, Turkey;Department of Basic Oncology, Dokuz Eylül University, Institute of Oncology, İzmir, Turkey.

Department of Basic Oncology, Dokuz Eylül University, Institute of Oncology, İzmir, Turkey.

出版信息

Acta Orthop Traumatol Turc. 2020 Jul;54(4):445-452. doi: 10.5152/j.aott.2020.20247.

Abstract

OBJECTIVE

The aim of this study was to show whether local application of cadmium-impregnated bone cement can induce apoptosis and decrease the viability of residual osteosarcoma (OS) cells in nude mice.

METHODS

K7M2 tumorigenic OS cell line was cultivated in vitro. The xenograft tumor model was formed by subcutaneously adding the tumor cells to athymic nude mice. Tumor was formed within 1 month. Then, mice were randomly assigned to five groups, each containing seven nude mice: control (group 1), wide resection (group 2), intralesional resection (group 3), intralesional resection + bone cement (group 4), and intralesional resection + cadmium embedded in bone cement (group 5). Tumor resection with 1 cm surgical margins was performed in the wide resection group. In intralesional resection groups, tumor tissue was resected with positive margins aiming to leave 15 mm3 of macroscopic tumor tissue. In group 3, the defect was left empty; groups 4 and 5 received bone cements prepared with saline and cadmium solutions, respectively. After the resection, mice were observed for 15 days and sacrificed. Next, surgical resection sites were evaluated histopathologically in each group.

RESULTS

Recurrent tumor was formed in all mice in the wide resection group, and apparent progression of residual tumor was observed in groups 3 and 4. On the contrary, only a thin layer of residual tumor was observed around the bone cement in group 5. Histological evaluation revealed remarkable necrosis in group 5 and lowest viability compared to other groups. No systemic toxic effect related to cadmium was observed.

CONCLUSION

Our data suggest that local application of cadmium in bone cement has a significant potential to increase tumor necrosis and decrease the viability of residual OS cells.

摘要

目的

本研究旨在探讨局部应用含镉骨水泥是否能诱导骨肉瘤(OS)细胞凋亡,降低裸鼠体内残留 OS 细胞的活力。

方法

体外培养 K7M2 致瘤性 OS 细胞系。通过将肿瘤细胞皮下注射到无胸腺裸鼠中构建异种移植肿瘤模型。1 个月内形成肿瘤。然后,将小鼠随机分为 5 组,每组 7 只裸鼠:对照组(第 1 组)、广泛切除术(第 2 组)、局部切除术(第 3 组)、局部切除术+骨水泥(第 4 组)和局部切除术+含镉骨水泥(第 5 组)。在广泛切除组中进行有 1 cm 手术切缘的肿瘤切除术。在局部切除术组中,肿瘤组织以阳性切缘切除,旨在留下 15 mm3 的肉眼可见肿瘤组织。第 3 组的缺损为空置;第 4 组和第 5 组分别接受用生理盐水和镉溶液制备的骨水泥。切除后,观察小鼠 15 天并处死。然后,在每组中评估手术切除部位的组织病理学。

结果

广泛切除组的所有小鼠均形成复发性肿瘤,第 3 组和第 4 组明显观察到残留肿瘤的进展。相反,第 5 组仅在骨水泥周围观察到一层薄薄的残留肿瘤。组织学评估显示第 5 组有明显的坏死,与其他组相比活力最低。未观察到与镉相关的全身毒性作用。

结论

我们的数据表明,局部应用含镉骨水泥具有显著增加肿瘤坏死和降低残留 OS 细胞活力的潜力。

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