Department of Orthopedic Oncology Surgery, Beijing Ji Shui Tan Hospital, Peking University, Beijing, China.
Am J Med Sci. 2012 Sep;344(3):199-205. doi: 10.1097/MAJ.0b013e31823e62e5.
Although there have been previous efforts to optimize dose intensity or change the chemotherapy protocol for osteosarcoma, long-term survival has not been markedly improved during the past 15 years.
Nude mice bearing established OS-732 human osteosarcoma received varying doses of Adriamycin, paclitaxel and Abraxane to assess tumor growth inhibition. For the dose-response experiments, mice were treated with the following agents at the indicated doses: (A) Adriamycin (2.5 mg/kg, ip), (B) paclitaxel (20 mg/kg, ip), (C-E) Abraxane (10, 20 and 40 mg/kg, ip, respectively) and (F) Saline (20 mg/kg, ip). All agents were administered every 4 days. Mean tumor volume and mice weight measurements were recorded every 3 days. Tumor weights were examined after mice were killed. Real-time polymerase chain reaction and Western blot were used to detect the expression levels of secreted protein, acidic and rich in cysteine (SPARC) in osteosarcoma specimens.
Administration of 40 mg/kg Abraxane showed a tumor inhibitory rate of 98.8% (tumor weight, 0.033 ± 0.044 g, P < 0.01), which was significantly higher than Adriamycin (46.1%, tumor weight, 1.455 ± 1.115 g, P < 0.01) and paclitaxel (40.8%, tumor weight, 1.597 ± 1.834 g, P < 0.05). Real-time polymerase chain reaction and Western blot showed higher expression of SPARC in tumor tissues than in normal tissues.
The antitumor effect of Abraxane was demonstrated in osteosarcoma xenografts in vivo. It suggests that SPARC tends to be highly expressed in osteosarcoma and further experiments need to explore its clinical relevance and the possible mechanisms.
尽管先前已经有过优化骨肉瘤的剂量强度或改变化疗方案的努力，但在过去的 15 年中，长期生存率并没有显著提高。
建立了携带 OS-732 人骨肉瘤的裸鼠接受不同剂量的阿霉素、紫杉醇和 Abraxane 以评估肿瘤生长抑制。在剂量反应实验中，以以下剂量对小鼠进行以下药物治疗：（A）阿霉素（2.5mg/kg，ip），（B）紫杉醇（20mg/kg，ip），（C-E）Abraxane（10、20 和 40mg/kg，ip），（F）生理盐水（20mg/kg，ip）。所有药物均每 4 天给药一次。每 3 天记录一次平均肿瘤体积和小鼠体重测量值。处死小鼠后检查肿瘤重量。使用实时聚合酶链反应和 Western blot 检测骨肉瘤标本中分泌蛋白、酸性和富含半胱氨酸（SPARC）的表达水平。
Abraxane 40mg/kg 给药组肿瘤抑制率为 98.8%（肿瘤重量，0.033±0.044g，P<0.01），明显高于阿霉素（46.1%，肿瘤重量，1.455±1.115g，P<0.01）和紫杉醇（40.8%，肿瘤重量，1.597±1.834g，P<0.05）。实时聚合酶链反应和 Western blot 显示肿瘤组织中 SPARC 的表达高于正常组织。
Abraxane 在骨肉瘤异种移植体内显示出抗肿瘤作用。这表明 SPARC 倾向于在骨肉瘤中高度表达，需要进一步的实验来探索其临床相关性和可能的机制。
