Interstitial pressure gradients in tissue-isolated and subcutaneous tumors: implications for therapy.
Interstitial pressure gradients in tissue-isolated and subcutaneous tumors: implications for therapy.
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发表时间：
1990-08
期刊：
影响因子：
11.2
通讯作者：
Y. Boucher;L. T. Baxter;R. Jain
中科院分区：
文献类型：
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作者：
Y. Boucher;L. T. Baxter;R. Jain
实体瘤中的高间质流体压力（IFP）与血流减少以及治疗剂（如单克隆抗体）的递送不足相关。在本研究中，IFP被测量为两个大鼠组织分离的肿瘤（乳腺腺癌R3230 AC，0.4-1.9 g，n = 9，和步行者256癌，0.5-5.0 g，n = 6）和一个皮下注射的肿瘤内径向位置的函数。肿瘤（乳腺腺癌R3230 AC，0.6-20.0 g，n = 7）。将连接到伺服零位压力监测系统的微量移液管（尖端直径2至4微米）引入到距肿瘤表面2.5至3.5mm的深度，并在将微量移液管取回到表面的同时测量IFP。大多数（86%）的压力曲线表明，在周边的大梯度，导致在肿瘤的深层几乎均匀的压力平台。在孤立的肿瘤内，压力在距离表面0.2至1.1 mm处达到平台值。在南卡罗来纳州。在皮肤中开始急剧增加，并在皮肤-肿瘤界面处趋于平稳。这些结果第一次证明IFP在整个肿瘤中升高，并且在肿瘤的周边或紧邻的周围组织中急剧下降至正常值。这些结果证实了我们最近发表的肿瘤间质液转运的数学模型的预测（Jain和巴克斯特，癌症研究，四十八：7022-7032，1988），提供了对间质性高血压病因学的新见解，并提出了改善治疗剂递送的可能策略。
High interstitial fluid pressure (IFP) in solid tumors is associated with reduced blood flow as well as inadequate delivery of therapeutic agents such as monoclonal antibodies. In the present study, IFP was measured as a function of radial position within two rat tissue-isolated tumors (mammary adenocarcinoma R3230AC, 0.4-1.9 g, n = 9, and Walker 256 carcinoma, 0.5-5.0 g, n = 6) and a s.c. tumor (mammary adenocarcinoma R3230AC, 0.6-20.0 g, n = 7). Micropipettes (tip diameters 2 to 4 microns) connected to a servo-null pressure-monitoring system were introduced to depths of 2.5 to 3.5 mm from the tumor surface and IFP was measured while the micropipettes were retrieved to the surface. The majority (86%) of the pressure profiles demonstrated a large gradient in the periphery leading to a plateau of almost uniform pressure in the deeper layers of the tumors. Within isolated tumors, pressures reached plateau values at a distance of 0.2 to 1.1 mm from the surface. In s.c. tumors the sharp increase began in skin and levelled off at the skin-tumor interface. These results demonstrate for the first time that the IFP is elevated throughout the tumor and drops precipitously to normal values in the tumor's periphery or in the immediately surrounding tissue. These results confirm the predictions of our recently published mathematical model of interstitial fluid transport in tumors (Jain and Baxter, Cancer Res., 48: 7022-7032, 1988), offer novel insight into the etiology of interstitial hypertension, and suggest possible strategies for improved delivery of therapeutic agents.