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苏拉单抗,一种新型抗血管生成药物,可抑制肿瘤生长和角膜新生血管形成。

Suramab, a novel antiangiogenic agent, reduces tumor growth and corneal neovascularization.

机构信息

Departments of Ophthalmology and Internal Medicine, Austral University Medical School and Austral University Hospital, Pilar, Buenos Aires, Argentina.

出版信息

Cancer Chemother Pharmacol. 2011 Mar;67(3):723-8. doi: 10.1007/s00280-010-1457-z. Epub 2010 Sep 21.

Abstract

PURPOSE

Oncological and ophthalmological diseases are increasingly treated with antiangiogenic agents. These agents have different intensities and duration of effects that should be considered to choose the most suitable therapy. Our purpose was to evaluate the synergistic effect of two drugs, jointly administered as a pharmaceutical compound, in two animal models.

METHODS

Corneal neovascularization was induced in three groups of nine white New Zealand rabbits, applying a filter paper disk soaked in 1 M NaOH on the central cornea (Ormerod et al., Invest Ophthalmol Vis Sci 30:2148-2153, 1989). Group one was treated immediately after injury with intravenous Suramab, compound of Bevacizumab + Suramin, and group two with intravenous Bevacizumab. A third group of non-treated rabbits was included as control group. Digital photographs were taken at days 9, 15, 21, and 35. Neovessel index (NVI) was calculated using the Image J Program. Neovessels formation was quantified and given a score from 0 to 4 to each quadrant according to the centripetal growth of the longest vessel. Colorectal animal model: 6- to 8-week-old male BALB/c mice were inoculated with cancer cells. Seven days after tumor inoculation, four groups of BALB/c mice were treated with intravenous Bevacizumab (n = 9); intravenous Suramin (n = 10); intravenous Suramab (n = 10); and intravenous saline solution (n = 4). Tumor growth was assessed twice weekly by caliper measurement.

RESULTS

The NVI was remarkably inferior in the group of rabbits treated with intravenous Suramab compared with controls after 35 days of follow-up. A greater inhibitory effect was obtained with Suramab compared to that obtained with Bevacizumab. Suramab significantly reduced tumor volume and prolonged survival of mice compared to controls.

CONCLUSIONS

Suramab strongly reduced neovascularization in a rabbit model of corneal angiogenesis and induced a potent antitumoral effect in mice.

摘要

目的

越来越多的肿瘤学和眼科疾病采用抗血管生成药物治疗。这些药物的作用强度和持续时间不同,应考虑选择最合适的治疗方法。我们的目的是评估两种药物联合给药的协同作用,这两种药物联合给药形成一种药物化合物,在两种动物模型中进行评估。

方法

三组共 9 只新西兰白兔的中央角膜应用浸有 1M NaOH 的滤纸盘诱导角膜新生血管(Ormerod 等人,Invest Ophthalmol Vis Sci 30:2148-2153, 1989)。一组在损伤后立即给予静脉注射 Suramab,Bevacizumab+Suramin 的复合物,另一组给予静脉注射 Bevacizumab。一组未治疗的兔子作为对照组。在第 9、15、21 和 35 天拍摄数字照片。使用 Image J 程序计算新生血管指数(NVI)。根据最长血管的向心性生长,对每个象限的新生血管形成进行量化,并给出 0 到 4 的评分。结直肠癌动物模型:6-8 周龄雄性 BALB/c 小鼠接种癌细胞。肿瘤接种后 7 天,四组 BALB/c 小鼠分别给予静脉注射 Bevacizumab(n=9);静脉注射 Suramin(n=10);静脉注射 Suramab(n=10);静脉注射生理盐水(n=4)。通过卡尺测量每周两次评估肿瘤生长。

结果

与对照组相比,静脉注射 Suramab 的兔组在随访 35 天后 NVI 明显降低。Suramab 比 Bevacizumab 具有更强的抑制作用。Suramab 显著降低了肿瘤体积并延长了小鼠的生存时间。

结论

Suramab 强烈抑制了兔角膜血管生成模型中的新生血管形成,并在小鼠中诱导了有效的抗肿瘤作用。

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