Suramin treatment of human glioma xenografts; effects on tumor vasculature and oxygenation status
Suramin treatment of human glioma xenografts; effects on tumor vasculature and oxygenation status
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DOI：
10.1023/a:1006363215260
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发表时间：
1999-09-01
影响因子：
3.9
通讯作者：
van der Kogel, AJ
中科院分区：
文献类型：
--
作者：
Bernsen, HJJA;Rijken, PFJW;van der Kogel, AJ
在这项研究中，苏拉明对裸鼠移植的人胶质瘤的肿瘤生长，血管和氧合的影响进行了检查。血管参数和氧合状态的异种移植物的肿瘤的冷冻切片中，使用缺氧标记物盐酸哌莫尼达唑检测缺氧区域化学测定。这些切片中的肿瘤血管通过内皮细胞标记物染色，并且在收获肿瘤之前通过施用灌注标记物Hoechst 333342使血管灌注可视化。用图像分析系统对血管参数进行定量分析。结果表明，苏拉明治疗后肿瘤生长明显减少。这种生长抑制伴随着血管结构的显著变化。尽管苏拉明治疗后肿瘤血管的总血管面积和灌注分数保持不变，但血管密度增加，表明治疗期间形成了更多但更小的血管结构。这些血管结构也更均匀地分布在肿瘤区域。对照肿瘤显示出广泛的缺氧区域，而在治疗的肿瘤中，缺氧区域大多消失。这种效应可能是由于治疗的肿瘤中均匀分布的灌注血管结构密度较高，导致肿瘤氧合增加。这些观察结果表明，苏拉明治疗可以导致显着的变化，不仅在肿瘤血管，而且在肿瘤氧合状态，可能有重要的后果，这些肿瘤的敏感性，如放射治疗。
In this study the effect of suramin on tumor growth, vascularity and oxygenation of a human glioma xenografted in the nude mouse was examined. Vascular parameters and oxygenation status of the xenografts were determined immunohistochemically in frozen sections of the tumors, using the hypoxia marker pimonidazole-hydrochloride to detect hypoxic areas. Tumor vessels in these sections were stained by an endothelial cell marker and perfusion of vessels was visualized by administration of the perfusion marker Hoechst 333342 before harvesting the tumors. The vascular parameters were quantified with an image analysis system. The results show that tumor growth was reduced considerably after suramin treatment. This growth suppression was accompanied by marked changes in vascular architecture. Although the total vascular area and perfused fraction of tumor vessels remained unchanged after suramin treatment, vascular density increased, indicating that more but smaller vessel structures had developed during therapy. These vessel structures were also more homogeneously spread over the tumor area. Control tumors showed extensive areas of hypoxia while in treated tumors hypoxic areas had mostly disappeared. This effect was probably due to the higher density of homogeneously distributed perfused vessel structures in the treated tumors, contributing to an increased oxygenation of the tumor. These observations suggest that suramin therapy can result in marked changes not only in tumor vascularity but also in tumor oxygenation status which may have important consequences for sensitivity of these tumors to other therapies such as radiation treatment.