Combined Anti-PLGF and Anti-Endostatin Treatments Inhibit Ocular Hemangiomas

Combined Anti-PLGF and Anti-Endostatin Treatments Inhibit Ocular Hemangiomas
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DOI:
10.1159/000430267
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发表时间:
2015-06
影响因子:
--
通讯作者:
Hua Jiang;Xinyi Wu;Hong Wang;Chao Huang;Linna Zhang
Hua Jiang;Xinyi Wu;Hong Wang;Chao Huang;Linna Zhang
中科院分区:
医学1区
文献类型:
--
作者:
Hua Jiang;Xinyi Wu;Hong Wang;Chao Huang;Linna Zhang

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背景/目的:新生血管的程度决定了眼部血管瘤(OH)的侵袭性。迄今为止,使用血管内皮生长因子A(VEGF-A)拮抗剂或内皮抑素的抗血管生成治疗并不总是导致令人满意的治疗结果。方法:我们检测了OH标本中VEGF受体1(VEGFR 1)的水平。我们比较了抗PLGF,内皮抑制素,以及它们的组合治疗对OH在小鼠模型中的生长的影响,在活体动物中使用生物发光成像。我们还通过CD 31表达检测了血管形成。结果:与配对的正常组织相比,我们在OH中检测到更高的VEGFR 1水平。因此,我们推测作为VEGFR 1的主要配体,胎盘生长因子(PLGF)也可能在OH的新生血管形成和肿瘤发生中发挥作用。在小鼠的植入OH模型中,我们发现抗PLGF和内皮抑制素均显著降低OH生长以及血管形成,而联合治疗具有显著更显著的效果。结论:我们的数据表明,联合抗PLGF和内皮抑素可能是一个更有效的治疗抑制眼部血管和肿瘤生长的OH。
Background/Aims: The degree of neovascularization determines the aggressiveness of ocular hemangiomas (OH). So far, the anti-angiogenic treatments using either antagonists against vascular endothelial growth factor A (VEGF-A), or endostatin, do not always lead to satisfactory therapeutic outcome. Methods: We examined the VEGF receptor 1 (VEGFR1) levels in the OH specimen. We compared the effects of anti-PLGF, endostatin, as well as their combined treatments on the growth of OH in a mouse model, using bioluminescence imaging in living animals. We also examined vascularization by CD31 expression. Results: We detected higher VEGFR1 levels in the OH, compared to paired normal tissue. Thus, we hypothesize that as a major ligand for VEGFR1, placental growth factor (PLGF) may also play a role in the neovascularization and tumorigenesis of OH. In an implanted OH model in mice, we found that both anti-PLGF and endostatin significantly decreased OH growth as well as vascularization, while combined treatments had a significantly more pronounced effect. Conclusion: Our data suggest that combined anti-PLGF and endostatin may be a more effective therapy for inhibition of ocular vascularization and the tumor growth in OH.