首页> 外文期刊>Molecular therapy: the journal of the American Society of Gene Therapy >Adenoviral vectors expressing human endostatin-angiostatin and soluble Tie2: enhanced suppression of tumor growth and antiangiogenic effects in a prostate tumor model.
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Adenoviral vectors expressing human endostatin-angiostatin and soluble Tie2: enhanced suppression of tumor growth and antiangiogenic effects in a prostate tumor model.

机译:表达人内皮抑素-血管抑制素和可溶性Tie2的腺病毒载体:在前列腺肿瘤模型中增强了对肿瘤生长的抑制作用和抗血管生成作用。

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Angiogenesis is essential for prostate cancer development and metastasis. Antiangiogenic therapy targeting tumor neovasculature, therefore, represents a promising approach for prostate cancer treatment. We hypothesized that adenoviral-mediated delivery of a combination of antiangiogenic factors might have an enhanced antitumor response. We developed the adenoviral vectors Ad-hEndo-angio, expressing a unique, chimeric human endostatin-angiostatin fusion protein, and Ad-sTie2, expressing a soluble form of endothelium-specific receptor tyrosine kinase Tie2. Matrigel angiogenesis assays using Ad-hEndo-angio revealed significant inhibition of tubular network formation and endothelial sprouting compared to Ad-sTie2. In vivo studies in a bilateral PC-3 tumor xenograft model following either intratumoral or systemic administration of Ad-hEndo-angio led to enhanced tumor growth suppression compared to Ad-sTie2. A novel finding is that an intratumoral, combination therapy employing one-half the dose of Ad-hEndo-angio as well as Ad-sTie2 led to a complete regression of the injected, as well as the contralateral uninjected, tumor and prolonged the tumor-free survival in 80% of the animals. In addition, a novel, real-time, intravital imaging modality was used to monitor antiangiogenic responses following adenoviral-mediated gene transfer. These results suggest that a combinatorial antiangiogenic gene therapy approach involving Ad-hEndo-angio and Ad-sTie2 could become a novel form of treatment for localized human prostate cancer.
机译:血管生成对于前列腺癌的发展和转移至关重要。因此,针对肿瘤新脉管系统的抗血管生成治疗代表了一种有前途的前列腺癌治疗方法。我们假设腺病毒介导的抗血管生成因子组合的传递可能具有增强的抗肿瘤反应。我们开发了表达独特,嵌合的人类内皮抑素-血管抑制素融合蛋白的腺病毒载体Ad-hEndo-angio和表达内皮特异性受体酪氨酸激酶Tie2的可溶性形式的Ad-sTie2。与Ad-sTie2相比,使用Ad-hEndo-angio进行的基质胶血管生成测定显示出对肾小管网络形成和内皮发芽的显着抑制。与Ad-sTie2相比,在肿瘤内或全身给药Ad-hEndo-血管瘤后,在双侧PC-3肿瘤异种移植模型中进行的体内研究导致肿瘤生长抑制作用增强。一个新发现是,采用一半剂量的Ad-hEndo-angio以及Ad-sTie2进行的肿瘤内联合治疗可导致注射的以及未注射的对侧肿瘤完全消退,并延长了肿瘤的持续时间。 80%的动物免费存活。此外,一种新型的实时活体成像方式被用于监测腺病毒介导的基因转移后的抗血管生成反应。这些结果表明,涉及Ad-hEndo-angio和Ad-sTie2的组合抗血管生成基因治疗方法可能成为局限性人前列腺癌的新型治疗形式。

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