摘要
背景:骨肉瘤是儿童期和年轻成年期最常见的恶性骨肿瘤。骨肉瘤患者的长期幸存者显示骨质疏松症和骨折发生率高。调节巨噬细胞活性的免疫调节性mifamurtide可改善疾病预后。 目的:评估mifamurtide对骨肉瘤巨噬细胞成分,破骨细胞在骨肉瘤儿童化疗中的作用。 方法:在存在或不存在mifamurtide的情况下收获从健康供体的外周血细胞获得的破骨细胞。此外,破骨细胞培养物从骨肉瘤患者获得,在开始和化疗期间,单独使用或与mifamurtide。通过生物分子(qPCR),生化分析(qPCR)分析原始骨质疏松酒石酸抗性酸性磷酸酶(TRAP),磷酸激酶-β-2(PKCβ2),1型(1)(TRPV1)和抗骨质疏松大麻素受体2型(CB2)生物标志物(Western Blotting)和形态学(TRAP测定)方法。 结果:来自骨肉瘤患者的破骨细胞相对于来自健康供体的破骨细胞的TRAP显着增加,CB2降低。这种破骨细胞多动症在化疗期间来自骨肉瘤患者的破骨细胞更明显。 Mifamurtide可减少健康供体骨质疏松的TRAP,PKCβ2,TRPV1水平,并增加破骨细胞中的CB2。此外,化学疗法诱导的骨吸收标记物的作用在化疗加mifamurtide骨肉瘤患者的破骨细胞中完全恢复。 结论:我们的数据表明,mifamurtide作为可能的抗吸收剂在骨肉瘤儿童化疗引起的骨质疏松症方面具有新的治疗作用。
关键词: 骨肉瘤相关骨丢失,吸收,破骨细胞活化,肿瘤结局,癌症相关疾病,骨肉瘤随访。
图形摘要
Current Cancer Drug Targets
Title:The Role of Mifamurtide in Chemotherapy-induced Osteoporosis of Children with Osteosarcoma
Volume: 17 Issue: 7
关键词: 骨肉瘤相关骨丢失,吸收,破骨细胞活化,肿瘤结局,癌症相关疾病,骨肉瘤随访。
摘要: Background: Osteosarcoma is the most frequent malignant bone tumor in childhood and young adulthood. Long-term survivors of osteosarcoma patients show high prevalence of osteoporosis and fractures. The immunomodulatory mifamurtide, which modulates macrophages activity, improves disease outcome.
Objective: To evaluate the role of mifamurtide on macrophage component of bone, the osteoclasts, during chemotherapy in children with osteosarcoma. Method: Osteoclasts, obtained from peripheral blood cells of healthy donors were harvested in the presence or not of mifamurtide. Moreover, osteoclast cultures were obtained from osteosarcoma patients, at onset and during chemotherapy, alone or with mifamurtide. Pro-osteoporotic tartrateresistant acid phosphatase (TRAP), phosphokinase-β-2 (PKCβ2), vanilloid receptor type 1 (TRPV1), and anti-osteoporotic cannabinoid receptor type 2 (CB2) biomarkers were analyzed by bio-molecular (qPCR), biochemical (Western Blotting), and morphological (TRAP assay) approaches. Results: Osteoclasts from osteosarcoma patients show significant increase of TRAP and decrease of CB2 with respect to osteoclasts from healthy donors. This osteoclast hyperactivity is more evident in osteoclasts from osteosarcoma patients during chemotherapy. Mifamurtide reduces pro-osteoporotic TRAP, PKCβ2, TRPV1 levels and increases CB2 in osteoclasts from healthy donors. Moreover, chemotherapy-induced effects on bone resorption markers are fully reverted in osteoclasts derived from osteosarcoma patients in chemotherapy plus mifamurtide. Conclusion: Our data suggest a new therapeutic role for mifamurtide as possible anti-resorption agent in chemotherapy-induced osteoporosis in children with osteosarcoma.Export Options
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Cite this article as:
The Role of Mifamurtide in Chemotherapy-induced Osteoporosis of Children with Osteosarcoma, Current Cancer Drug Targets 2017; 17 (7) . https://dx.doi.org/10.2174/1568009616666161215163426
DOI https://dx.doi.org/10.2174/1568009616666161215163426 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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