Microvascular architecture in a mammary carcinoma: branching patterns and vessel dimensions.

Microvascular architecture in a mammary carcinoma: branching patterns and vessel dimensions.
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DOI:
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发表时间:
1991
期刊:
影响因子:
11.2
通讯作者:
J. R. Less;T. Skalak;E. Sevick;R. Jain
J. R. Less;T. Skalak;E. Sevick;R. Jain
中科院分区:
医学1区
文献类型:
--
作者:
J. R. Less;T. Skalak;E. Sevick;R. Jain

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这项工作的目的是介绍一种肿瘤血管分类方案,并提供第一个定量测量的血管分支模式和相关的血管尺寸在乳腺癌。在大鼠卵巢组织分离的肿瘤制备物中生长的乳腺腺癌R3230 AC肿瘤用巴特森17号聚合物输注,并在聚合期间维持在50 mm Hg的血管内压力。在KOH中浸渍肿瘤允许可视化脉管系统。在4个肿瘤(4-5 g)中测量血管分支模式、长度和直径。离心排序方案是专门设计的,以考虑肿瘤微血管网络拓扑结构的独特功能。动脉网络揭示了两种类型的分支模式。一种类型的小动脉网络表现出血管直径和长度随着分支顺序的增加而减少。在第二种类型的网络中,血管的直径和长度在较高世代的两个变量中显示出波动。肿瘤中存在无血管和血管化不良的区域,毛细血管供应稀少,但对血管化区域中的几个毛细血管网络的分析显示了相互连接的血管的非平面网络。网状物由平均段长度为67微米、平均直径为10微米、平均毛细管间距为49微米的血管组成。毛细血管路径长度范围为0.5至1.5 mm。因此,肿瘤毛细血管直径大于大多数正常组织,在毛细血管网络存在的区域,毛细血管间距在正常范围内。在静脉网中,第一至第九级小静脉的直径从650微米减小到20微米。小静脉长度从5到0.5毫米的第一至第四顺序,但相当均匀(小于500微米)为更高的订单。总之,实体瘤血管结构虽然表现出与正常组织中观察到的相似的几个特征,但具有在正常组织中不常见的其他特征。肿瘤微循环的这些特征可能导致局部血细胞比容、氧张力和药物浓度的异质性,从而降低当今癌症治疗的功效。
The objective of this work was to introduce a tumor vessel classification scheme and to provide the first quantitative measurements of vessel branching patterns and the related vascular dimensions in a mammary carcinoma. Mammary adenocarcinoma R3230AC tumors, grown in the rat ovarian tissue-isolated tumor preparation, were infused with Batson's No. 17 polymer and maintained at an intravascular pressure of 50 mm Hg during polymerization. Maceration of the tumor in KOH allowed visualization of the vasculature. The vessel branching patterns, lengths, and diameters were measured in four tumors (4-5 g). A centrifugal ordering scheme was devised specifically to account for the unique features of tumor microvascular network topology. The arterial networks revealed two types of branching patterns. One type of arteriolar network exhibited decreasing vessel diameters and lengths with increasing branch order. In a second type of network, the diameter and length of the vessels displayed fluctuations in both variables at higher generations. Avascular and poorly vascularized regions with sparse capillary supply were present in the tumors, but analysis of several capillary networks in vascularized regions revealed a nonplanar meshwork of interconnected vessels. The meshworks were composed of vessels with a mean segment length of 67 microns, a mean diameter of 10 microns, and a mean intercapillary distance of 49 microns. Capillary path lengths ranged from 0.5 to 1.5 mm. Thus, tumor capillary diameter was greater than that in most normal tissues and, in the regions where capillary networks existed, intercapillary spacing was in the normal range. In the venous network, diameters decreased from 650 to 20 microns for the first to ninth order venules. Venule length decreased from 5 to 0.5 mm for first to fourth order but was fairly uniform (less than 500 microns) for higher orders. In conclusion, solid tumor vascular architecture, while exhibiting several features that are similar to those observed in normal tissues, has others that are not commonly seen in normal tissues. These features of the tumor microcirculation may lead to heterogeneous local hematocrits, oxygen tensions, and drug concentrations, thus reducing the efficacy of present day cancer therapies.