Intravenous administration of the conditionally replicative adenovirus Ad5-Δ24RGD induces regression of osteosarcoma lung metastases
Intravenous administration of the conditionally replicative adenovirus Ad5-Δ24RGD induces regression of osteosarcoma lung metastases
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DOI：
10.1186/1476-4598-7-9
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发表时间：
2008-01-23
期刊：
影响因子：
37.3
通讯作者：
Wuisman, Paul I. J. M.
中科院分区：
文献类型：
--
作者：
Graat, Harm C. A.;van Beusechem, Victor W.;Wuisman, Paul I. J. M.
转移性骨肉瘤(OS)预后很差。因此，需要新的治疗方法。条件复制型腺病毒Ad5-Delta 24RGD在包括OS在内的局部肿瘤中显示出良好的抗肿瘤作用。本研究的目的是确定静脉注射Ad5-Delta 24RGD是否能抑制人OS肺转移瘤的生长。在接种肿瘤细胞后1、2、3周或5、6、7周，用Ad5-Delta 24RGD治疗SAOS-lm7 OS肺转移瘤小鼠。1-3周的病毒治疗对肺重量和总体重没有统计学意义的影响。然而，肉眼可见的肺瘤结节的数量从PBS处理的对照组小鼠的中位数158减少到Ad5-Delta 24RGD处理的小鼠的58(p=0.15)。此外，与PBS治疗的对照组相比，第5-7周治疗的小鼠显示出显著的肺重量减少(肿瘤质量减少，p<；0.005)，体重增加(疾病症状减少，p<；005)和肉眼观察的肺部肿瘤结节的数量减少(中位数60对149，p=0.12)。在最后一次静脉腺病毒注射三周后，在肺肿瘤结节中检测到腺病毒六邻体的表达，这表明病毒感染正在进行。这些发现表明，全身性给药Ad5-Delta 24RGD可能是治疗转移性骨肉瘤的一种有前途的新策略。
Metastatic osteosarcoma (OS) has a very poor prognosis. New treatments are therefore wanted. The conditionally replicative adenovirus Ad5-Delta 24RGD has shown promising anti-tumor effects on local cancers, including OS. The purpose of this study was to determine whether intravenous administration of Ad5-Delta 24RGD could suppress growth of human OS lung metastases. Mice bearing SaOs-lm7 OS lung metastases were treated with Ad5-Delta 24RGD at weeks 1, 2 and 3 or weeks 5, 6 and 7 after tumor cell injection. Virus treatment at weeks 1-3 did not cause a statistically significant effect on lung weight and total body weight. However, the number of macroscopic lung tumor nodules was reduced from a median of > 158 in PBS-treated control mice to 58 in Ad5-Delta 24RGD-treated mice (p = 0.15). Moreover, mice treated at weeks 5-7 showed a significantly reduced lung weight (decrease of tumor mass, p < 0.05), a significantly increased body weight gain (decrease of disease symptoms, p < 0.005) and a reduced number of macroscopic lung tumor nodules (median 60 versus > 149, p = 0.12) compared to PBS-treated control animals. Adenovirus hexon expression was detected in lung tumor nodules at sacrifice three weeks after the last intravenous adenovirus administration, suggesting ongoing viral infection. These findings suggest that systemic administration of Ad5-Delta 24RGD might be a promising new treatment strategy for metastatic osteosarcoma.