A highly sensitive model for quantification of in vivo tumor angiogenesis induced by alginate-encapsulated tumor cells.

A highly sensitive model for quantification of in vivo tumor angiogenesis induced by alginate-encapsulated tumor cells.
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DOI:
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发表时间:
1997-09
期刊:
影响因子:
11.2
通讯作者:
J. Hoffmann;M. Schirner;A. Menrad;Martin R. Schneider
J. Hoffmann;M. Schirner;A. Menrad;Martin R. Schneider
中科院分区:
医学1区
文献类型:
--
作者:
J. Hoffmann;M. Schirner;A. Menrad;Martin R. Schneider

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一个显着的方法,一个特定的肿瘤血管生成模型在体内是使用海藻酸盐植入物封装肿瘤细胞。然而,这种先前报道的方法经常受到质疑,因为怀疑海藻酸盐植入物中血红蛋白作为血管化参数的相关性。在本研究中,我们研究了使用高分子量的血池试剂FITC-葡聚糖是否会显著改善藻酸盐植入物处的血管形成测定。在我们的实验中,我们发现静脉推注后,FITC-葡聚糖在小鼠血液循环中快速分布。藻酸盐植入物内FITC-葡聚糖的量与包封的LL 2癌细胞或B16/F10细胞的数量密切相关。即使每个藻酸盐植入物10(3)个细胞的低数量也会导致FITC-葡聚糖的累积显著增加。用含有10(4)个LL 2或B16/F10肿瘤细胞的藻酸盐植入物发现了超过对照组10倍的刺激。在不同的治疗方案中使用研究化合物AGM-1470,我们发现用FITC-葡聚糖定量藻酸盐植入物血管生成是测定血管生成抑制的灵敏方法。总之,我们的结果表明,使用FITC-葡聚糖能够高度灵敏地定量测量藻酸盐植入物的血管形成。
A remarkable approach to a specific tumor angiogenesis model in vivo is the use of alginate implants encapsulating tumor cells. However, this previously reported approach has often been questioned because of doubts regarding the relevance of hemoglobin at the alginate implant as a parameter of vascularization. In the present investigation, we examined whether or not the use of the blood pool agents FITC-dextran of high molecular weight would significantly improve the determination of vascularization at the alginate implant. In our experiments, we found a rapid distribution of FITC-dextran within the blood circulation of mice after i.v. bolus injection. The amount of FITC-dextran within alginate implants strongly correlated with the number of LL2 carcinoma cells or B16/F10 cells encapsulated. Even a low number of 10(3) cells per alginate implant led to a significantly increased accumulation of FITC-dextran. A more than 10-fold stimulation above that of controls was found with alginate implants containing 10(4) LL2 or B16/F10 tumor cells. Using the investigational compound AGM-1470 in different treatment schedules, we found that quantification of alginate implant anglogenesis with FITC-dextran is a sensitive method for the determination of angiogenesis inhibition. In conclusion, our results demonstrated that the use of FITC-dextran enables highly sensitive, quantitative measurement of blood vessel formation by alginate implants.