PDF(Pubmed)
Abstract：
UNASSIGNED: Zoledronic acid (ZOL) is a third-generation bisphosphonate with a higher affinity for bone resorption areas than earlier bisphosphonates (i.e., pamidronate, PAM). In human medicine, ZOL provides improved bone pain relief and prolonged time to skeletal-related events compared to its older generational counterparts. Preclinical studies have investigated its role as an anti-neoplastic agent, both independently and synergistically, with radiation therapy (RT). ZOL and RT act synergistically in several neoplastic human cell lines: prostate, breast, osteosarcoma, and fibrosarcoma. However, the exact mechanism of ZOL\'s radiosensitization has not been fully elucidated.
UNASSIGNED: We investigated ZOL\'s ability to induce apoptosis in canine osteosarcoma cell lines treated with various doses of megavoltage external beam radiotherapy. Second, we evaluated cell cycle arrest in ZOL-treated cells to assess several neo-adjuvant time points. Finally, we treated 20 dogs with naturally occurring appendicular OS with 0.1 mg/kg ZOL IV 24 h before receiving 8 Gy of RT (once weekly fraction x 4 weeks).
UNASSIGNED: We found that apoptosis was increased in all ZOL-treated cell lines compared to controls, and the combination of ZOL and RT resulted in dissimilar apoptosis between Abrams and D-17 and HMPOS cell lines. Cell cycle arrest (G2/M phase) was minimal and variable between cell lines but perhaps greatest at 48 h post-ZOL treatment. Only 10% of dogs treated with ZOL and RT developed pathologic fractures, compared to 44% of dogs historically treated with PAM and RT (p = 0.027).
UNASSIGNED: ZOL and RT appear to be a well-tolerated combination treatment scheme for non-surgical candidates; future studies must elucidate the ideal timing of ZOL.
UNASSIGNED: We investigated ZOL\'s ability to induce apoptosis in canine osteosarcoma cell lines treated with various doses of megavoltage external beam radiotherapy. Second, we evaluated cell cycle arrest in ZOL-treated cells to assess several neo-adjuvant time points. Finally, we treated 20 dogs with naturally occurring appendicular OS with 0.1 mg/kg ZOL IV 24 h before receiving 8 Gy of RT (once weekly fraction x 4 weeks).
UNASSIGNED: We found that apoptosis was increased in all ZOL-treated cell lines compared to controls, and the combination of ZOL and RT resulted in dissimilar apoptosis between Abrams and D-17 and HMPOS cell lines. Cell cycle arrest (G2/M phase) was minimal and variable between cell lines but perhaps greatest at 48 h post-ZOL treatment. Only 10% of dogs treated with ZOL and RT developed pathologic fractures, compared to 44% of dogs historically treated with PAM and RT (p = 0.027).
UNASSIGNED: ZOL and RT appear to be a well-tolerated combination treatment scheme for non-surgical candidates; future studies must elucidate the ideal timing of ZOL.
摘要：
■唑来膦酸（ZOL）是第三代双膦酸盐，与早期的双膦酸盐相比，对骨吸收区域的亲和力更高（即，帕米膦酸盐,PAM）。在人类医学中，与老一代相比，ZOL提供了改善的骨骼疼痛缓解和延长的骨骼相关事件时间。临床前研究已经调查了其作为抗肿瘤剂的作用，既独立又协同，放射治疗（RT）。ZOL和RT在几种肿瘤人类细胞系中协同作用：前列腺，乳房,骨肉瘤,和纤维肉瘤.然而,ZOL放射增敏的确切机制尚未完全阐明。
■我们研究了用各种剂量的兆伏外束放射治疗治疗的犬骨肉瘤细胞系中ZOL诱导细胞凋亡的能力。第二,我们评估了ZOL处理细胞中的细胞周期停滞,以评估几个新佐剂时间点.最后,我们在接受8GyRT(每周一次×4周)前24小时用0.1mg/kgZOLIV治疗了20只患有自然阑尾OS的狗。
■我们发现，与对照组相比，所有ZOL处理的细胞系中细胞凋亡都增加了，ZOL和RT的组合导致艾布拉姆斯和D-17和HMPOS细胞系之间不同的凋亡。细胞周期停滞（G2/M期）是最小的，并且在细胞系之间是可变的，但在ZOL处理后48小时可能最大。只有10％的ZOL和RT治疗的狗发生病理性骨折，相比之下，44%的狗历史上接受PAM和RT治疗（p=0.027）。
■ZOL和RT似乎是非手术候选者的耐受性良好的联合治疗方案；未来的研究必须阐明ZOL的理想时机。
■我们研究了用各种剂量的兆伏外束放射治疗治疗的犬骨肉瘤细胞系中ZOL诱导细胞凋亡的能力。第二,我们评估了ZOL处理细胞中的细胞周期停滞,以评估几个新佐剂时间点.最后,我们在接受8GyRT(每周一次×4周)前24小时用0.1mg/kgZOLIV治疗了20只患有自然阑尾OS的狗。
■我们发现，与对照组相比，所有ZOL处理的细胞系中细胞凋亡都增加了，ZOL和RT的组合导致艾布拉姆斯和D-17和HMPOS细胞系之间不同的凋亡。细胞周期停滞（G2/M期）是最小的，并且在细胞系之间是可变的，但在ZOL处理后48小时可能最大。只有10％的ZOL和RT治疗的狗发生病理性骨折，相比之下，44%的狗历史上接受PAM和RT治疗（p=0.027）。
■ZOL和RT似乎是非手术候选者的耐受性良好的联合治疗方案；未来的研究必须阐明ZOL的理想时机。
