Magnetic resonance imaging for monitoring the effects of thalidomide on experimental human breast cancers
Magnetic resonance imaging for monitoring the effects of thalidomide on experimental human breast cancers
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DOI：
10.1007/s00330-008-1111-x
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发表时间：
2009-01-01
影响因子：
5.9
通讯作者：
Brasch, Robert C.
中科院分区：
文献类型：
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作者：
Cyran, Clemens C.;Sennino, Barbara;Brasch, Robert C.
沙利度胺可抑制某些肿瘤类型的血管生成，可减少人类乳腺癌模型中大分子造影剂（MMCM）的外渗，通过MMCM增强动态磁共振成像（MRI）和荧光显微镜在同一肿瘤中进行检测。经过 1 周、三剂沙利度胺疗程后，平均 MRI 测定的内皮转移系数 K-PS 显着下降 (p < 0.05)，从 19.4 +/- 9.1 降至 6.3 +/- 9.1 μl/min 中心点 100 cm(3)。相应地，沙利度胺治疗的肿瘤（18.6 A +/- 11.9%）中外渗 MMCM 的显微测量（以链霉亲和素染色的分数面积表示）显着（p < 0.05）低于对照盐水治疗的肿瘤（50.2 A +/- 2.3%）。在逐个肿瘤的基础上，治疗后 K-PS 值与 MMCM 外渗的显微镜测量显着相关（r (2) = 0.55，p < 0.05）。然而，在生理盐水和沙利度胺治疗的肿瘤之间，在生长速率、血管丰富度或含有 VEGF 的细胞数量方面没有观察到显着差异。由于其对检测肿瘤血管渗漏变化的敏感性，这种 MMCM 增强的 MRI 检测可用于监测沙利度胺对个体患者的影响。 MMCM 外渗的 MRI 和荧光显微镜测量之间的显着相关性支持使用非侵入性 MRI 方法来评估沙利度胺对肿瘤血管的作用。
Thalidomide, which inhibits angiogenesis in certain tumor types, reduced extravasation of a macromolecular contrast medium (MMCM) in a human breast cancer model as assayed by MMCM-enhanced dynamic magnetic resonance imaging (MRI) and fluorescence microscopy in the same tumors. After a 1-week, three-dose course of thalidomide, the mean MRI-assayed endothelial transfer coefficient, K-PS, decreased significantly (p < 0.05) from 19.4 +/- 9.1 to 6.3 +/- 9.1 mu l/min center dot 100 cm(3). Correspondingly, microscopic measurements of extravasated MMCM, expressed as fractional area of streptavidin staining, were significantly (p < 0.05) lower in thalidomide-treated tumors (18.6 A +/- 11.9%) than in control saline-treated tumors (50.2 A +/- 2.3%). On a tumor-by-tumor basis, post-treatment K-PS values correlated significantly (r (2) = 0.55, p < 0.05) with microscopic measures of MMCM extravasation. However, no significant differences were observed between saline- and thalidomide-treated tumors with respect to rate of growth, vascular richness, or amount of VEGF-containing cells. Because of its sensitivity to the detection of changes in vascular leakage in tumors, this MMCM-enhanced MRI assay could prove useful for monitoring the effects of thalidomide on an individual patient basis. The significant correlation between MRI and fluorescence microscopic measures of MMCM extravasation supports the utility of the non-invasive MRI approach for assessing the action of thalidomide on tumor blood vessels.