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贝伐珠单抗、恩度和安罗替尼在转基因和人肺癌异种移植斑马鱼模型中的疗效和毒性比较。

Comparison of efficacy and toxicity of bevacizumab, endostar and apatinib in transgenic and human lung cancer xenograftzebrafish model.

机构信息

Department of Oncology, the Second Affiliated Hospital, Harbin Medical University, Harbin, 150001, P. R. China.

出版信息

Sci Rep. 2018 Oct 26;8(1):15837. doi: 10.1038/s41598-018-34030-5.

Abstract

The poor prognosis in non-small-cell lung cancer has driven the development of novel targeted therapies. Vascular endothelial growth factor is the most potent force in mediating tumor angiogenesis, and many angiogenesis inhibitors have been developed for oncology treatment. We performed a study to characterize the efficacy, safety and tumor suppression of three lung cancer related anti-angiogenic drugs (bevacizumab, endostar and apatinib) using transgenic zebrafish embryo and human lung cancer xenotransplantation model. All three drugs demonstrated remarkable angiogenesis and tumor inhibition effect in the zebrafish model, within the nonlethal dose range. Endostar and bevacizumab showed competitive anti-tumor efficacy. The anti-tumor performance of apatinib was hamstrung by its elevated toxicity at 35 °C. The addition of pemetrexed to anti-angiogenesis therapy had no obvious additional benefit in tumors.

摘要

非小细胞肺癌预后较差,这推动了新型靶向治疗的发展。血管内皮生长因子是介导肿瘤血管生成的最有效因素,许多血管生成抑制剂已被开发用于肿瘤治疗。我们使用转基因斑马鱼胚胎和人肺癌异种移植模型,研究了三种肺癌相关抗血管生成药物(贝伐珠单抗、恩度和阿帕替尼)的疗效、安全性和肿瘤抑制作用。在非致死剂量范围内,这三种药物在斑马鱼模型中均表现出显著的血管生成和肿瘤抑制作用。恩度和贝伐珠单抗显示出竞争性的抗肿瘤疗效。阿帕替尼的抗肿瘤性能受到 35°C 时毒性升高的限制。培美曲塞联合抗血管生成治疗对肿瘤没有明显的额外获益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64e7/6203857/73d63ba3b74b/41598_2018_34030_Fig1_HTML.jpg

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