Vascular permeability and microcirculation of gliomas and mammary carcinomas transplanted in rat and mouse cranial windows.
Vascular permeability and microcirculation of gliomas and mammary carcinomas transplanted in rat and mouse cranial windows.
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发表时间：
1994-09
期刊：
影响因子：
11.2
通讯作者：
Fan Yuan;H. A. Salehi;Y. Boucher;U. Vasthare;R. Tuma;R. Jain
中科院分区：
文献类型：
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作者：
Fan Yuan;H. A. Salehi;Y. Boucher;U. Vasthare;R. Tuma;R. Jain
许多脑肿瘤对化疗具有高度抵抗性，可能是由于存在紧密的血液肿瘤屏障。为了更好地了解脑环境对这种屏障的调节，通过将肿瘤组织移植到大鼠和小鼠的颅窗中建立了一种新的活体显微镜模型。该模型的特点是红细胞速度，血管直径和血管通透性的各种肿瘤：R3230 AC（大鼠乳腺癌），MCaIV（小鼠乳腺癌），U87和HGL 21（人类恶性星形细胞瘤）。我们的研究结果表明，肿瘤的血流量在颅窗是一个到三个数量级低于软脑膜血管中的血流量和类似的背皮褶室在以前的研究中观察到的。平均血管直径范围为HGL 21的6.8 +/- 1.3 μ m至MCaIV的30.4 +/- 8.5 μ m。在肿瘤细胞系之间观察到血管对白蛋白的渗透性至少有一个数量级的差异：HGL 21为0.11 +/- 0.05 x 10（-7）cm/s，而U87为3.8 +/- 1.2 x 10（-7）cm/s。荧光素钠和丽丝胺绿色注射也证实了HGL 21的低血管渗透性，这表明并非所有肿瘤都对示踪分子渗漏，并且该肿瘤的血-肿瘤屏障仍然具有在其他颅内肿瘤中观察到的血-脑屏障的一些特征。本文提出的模型将使我们能够操纵脑肿瘤中的血管通透性，从而可能提供关于调节血肿瘤屏障的新信息和改善脑肿瘤中药物递送的新策略。
Many brain tumors are highly resistant to chemotherapy, presumably due to the presence of a tight blood-tumor barrier. For a better understanding of the regulation of this barrier by the brain environment, a new intravital microscopy model was established by transplanting tumor tissue into cranial windows in both rats and mice. The model was characterized by RBC velocities, vessel diameters, and vascular permeabilities of various tumors: R3230AC (a rat mammary adenocarcinoma), MCaIV (a mouse mammary adenocarcinoma), and U87 and HGL21 (human malignant astrocytomas). Our results showed that tumor blood flow in cranial windows was one to three orders of magnitude lower than the blood flow in pial vessels and similar to that in dorsal skin-fold chambers observed in previous studies. The mean vessel diameter ranged from 6.8 +/- 1.3 microns for HGL21 to 30.4 +/- 8.5 microns for MCaIV. At least one order of magnitude difference in vascular permeability to albumin was observed between tumor lines: 0.11 +/- 0.05 x 10(-7) cm/s for HGL21 versus 3.8 +/- 1.2 x 10(-7) cm/s for U87. The low vascular permeability of HGL21, which was also confirmed by both sodium fluorescein and Lissamine green injections, suggests that not all tumors are leaky to tracer molecules and that the blood-tumor barrier of this tumor still possesses some characteristics of blood-brain barrier as observed in other intracranial tumors. The model presented here will allow us to manipulate the vascular permeability in brain tumors and thus may provide new information on the regulation of the blood-tumor barrier and new strategies for improving drug delivery in brain tumors.