Blood tumor permeability of experimental brain tumor: An electron microscopic study using lanthanum
Blood tumor permeability of experimental brain tumor: An electron microscopic study using lanthanum
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DOI：
10.1111/j.1440-1789.2004.00575.x
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发表时间：
2005-03-01
期刊：
影响因子：
2.3
通讯作者：
Kawamoto, K
中科院分区：
文献类型：
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作者：
Kato, T;Tsuchida, T;Kawamoto, K
为了评估实验性脑肿瘤模型中微血管的通透性，使用镧离子（La 3+）作为低分子量电子显微镜探针。将大鼠胶质瘤9 L和腺癌ACL 15移植到大鼠脑内和侧腹下。然后将大鼠麻醉，依次灌注生理盐水、生理盐水加La 3+，然后灌注磷酸盐缓冲液中的固定剂。取出脑和皮下肿瘤，进一步固定，并进行电子显微镜检查。La ~（3+）不通过正常脑血管内皮细胞的紧密连接。同样地，La 3+在移植的脑肿瘤中没有穿透微血管的内皮细胞壁。相反，观察到移植的皮下肿瘤中的微血管中的La 3+外渗。电镜观察结果表明，La 3+透过内皮细胞壁的主要机制是囊泡转运。由于大多数类似于La ~（3+）的化疗药物都是低分子量的，因此我们可以从我们目前的研究结果表明，在大鼠脑胶质瘤移植模型中，抗癌药物的血液肿瘤渗透性不同于在大鼠皮下胶质瘤运输模型中。换句话说，我们的结果表明，当皮下胶质瘤移植模型用于抗癌药物的敏感性试验时，可能很难预测体内的抗肿瘤作用。
In an attempt to assess the permeability of microvessels in the experimental brain tumor model, lanthanum ion (La3+) was used as a low-molecular weight electron microscopic probe. Rat glioma 9 L and adenocarcinoma ACL15 were transplanted to the brain and subflank of rats. The rats were then anesthetized sequentially perfused with saline, saline plus La3+ followed by a fixative in phosphate buffer. The brain and subcutaneous tumors were removed, further fixed, and processed for electron microscopy. La3+ did not pass through the tight junctions of the normal cerebral endothelium. Similarly, La3+ did not penetrate the endothelial cell wall of the microvessels in the transplanted brain tumors. In contrast, extravasation of La3+ from the microvessels in the transplanted subcutaneous tumors was observed. The electron microscopy examination results indicate that the vesicular transport was a predominant mechanism in the penetration of La3+ through the endothelial cell wall. Since most chemotherapeutic agents similar as La3+ are of low molecular weight, we can suggest from the results of our present study that the blood tumor permeability of the anti-cancer agents in the rat model of brain glioma transplantation differs from that in the rat model of subcutaneous glioma transportation. In other words, our results indicate that when the subcutaneous glioma transplantation model is used in sensitivity tests of anti-cancer agents, it will possibly be very difficult to predict the anti-neoplastic effect in vivo.