Endostatin therapy reveals a U-shaped curve for antitumor activity.
Endostatin therapy reveals a U-shaped curve for antitumor activity.
复制标题
内皮抑素治疗显示抗肿瘤活性呈 U 形曲线。
DOI：
10.1038/sj.cgt.7700938
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Javaherian,K
中科院分区：
文献类型：
--
作者：
TjinThamSjin,RM;Naspinski,J;Birsner,AE;Li,C;Chan,R;Lo,K-M;Gillies,S;Zurakowski,D;Folkman,J;Samulski,J;Javaherian,K
开发内皮抑制素的持续全身递送一直是许多实验室的目标。我们采用了一种利用不同病毒构建体的基因治疗方法。在这里，我们报告了一种新的血清型的腺相关病毒，其中包括犬内皮抑素，在小鼠肌肉注射后，提供剂量依赖性的转基因表达的循环。内皮抑制素水平升高在循环中保持稳定至少4个月。体外实验表明，表达的蛋白具有生物活性。上述构建体的抗肿瘤活性显示出U形曲线，其中在某一临界浓度范围内观察到最大活性。这些数据表明，可能需要最佳剂量范围才能在大型动物模型中达到治疗效果。
Developing continuous systemic delivery of endostatin has been a goal of many laboratories. We have employed a method of gene therapy utilizing different viral constructs. Here, we report that a new serotype of adeno-associated viruses, which incorporates canine endostatin, provides dose-dependent transgene expression in the circulation after intramuscular injection in mice. Elevated levels of endostatin remained stable in the circulation for at least 4 months. In vitro assays determined that the protein expressed was biologically active. Antitumor activities of the above construct demonstrated a U-shape curve, where the maximum activity was observed within a certain critical concentration range. These data suggest that an optimum dose range may be required to achieve therapeutic efficacy in large animal models.