Rabes H M, Carl P, Meister P, Rattenhuber U
Cancer. 1979 Sep;44(3):799-813. doi: 10.1002/1097-0142(197909)44:3<799::aid-cncr2820440303>3.0.co;2-d.
Vascular perfusion of 16 renal adenocarcinomas with radioactive DNA precursors provides a possibility of characterize proliferative compartments of this tumor type. Immediately after resection of the tumor-bearing kidney, the organ is perfused via renal artery with dextran-diluted, heparinized oxygenated blood at physiological temperature, pH, flow, and pressure in a recirculation system. DNA synthetizing cells are labeled by addition of 3H- or 14C-thymidine or both isotopes at different intervals. Beta camera scans and whole-tumor autoradiograms disclose a striking proliferative heterogeneity of the tumor. Cell proliferation depends on intratumoral localization, cellular differentiation, histological structure and vascular supply. Subpopulations of high proliferative activity are found at the invasive borderline near normal kidney, focally in subcapsular areas and in intrarenal metastases, but also immediately adjacent to necrotic areas in the tumor center. Quantitative evaluation of autoradiograms yields, at the cellular level, a significantly higher labeling index in granular cells (3.21%) than in clear cells (0.65%), with a large variability dependent on the histological structure. The highest number of DNA synthetizing cells is seen in papillary and mixed solid-tubular zones and at peripheral parts of solid areas, whereas in central parts of solid tumor cords and in highly differentiated tubular areas lower labeling indices are observed. The labeling index decreases exponentially as a function of the distance from the supporting blood vessel. In solid cords, no labeled cells are seen at a distance of more than 200 micron from the capillary. The ts determined by 3H/14C-thymidine double labeling is between 9.9 and 16.8 hr for granular cells and about 9.2 hr for clear cells. Potential population doubling time calculated for various subpopulations yields values between 4 and 50 days. It is concluded that cell loss is high, for granular cells in particular. Besides cell loss, a large nonproliferating compartment contributes to a delay of the tumor volume doubling time. Proliferative heterogeneity of advanced human tumors, as exemplified by the renal adenocarcinoma, bears important implications for therapy and prognosis.
用放射性DNA前体对16例肾腺癌进行血管灌注，为表征这种肿瘤类型的增殖区室提供了可能。在切除患肾后，立即在循环系统中，于生理温度、pH值、血流和压力条件下，经肾动脉用葡聚糖稀释、肝素化的含氧血液对该器官进行灌注。通过在不同时间间隔添加³H - 或¹⁴C - 胸腺嘧啶核苷或两种同位素，对DNA合成细胞进行标记。β相机扫描和全肿瘤放射自显影片揭示了肿瘤显著的增殖异质性。细胞增殖取决于肿瘤内定位、细胞分化、组织结构和血管供应。在靠近正常肾的浸润边缘、包膜下区域局部以及肾内转移灶中发现具有高增殖活性的亚群，但也在肿瘤中心紧邻坏死区域处发现。放射自显影片的定量评估在细胞水平上显示，颗粒细胞的标记指数（3.21%）显著高于透明细胞（0.65%），且因组织结构不同而有很大差异。在乳头状和混合实性 - 管状区域以及实性区域周边部分可见到数量最多的DNA合成细胞，而在实性肿瘤条索的中央部分和高分化管状区域观察到较低的标记指数。标记指数随距供养血管距离的增加呈指数下降。在实性条索中，距毛细血管超过200微米处未见标记细胞。通过³H/¹⁴C - 胸腺嘧啶核苷双重标记测定的颗粒细胞的ts在9.9至16.8小时之间，透明细胞约为9.2小时。为不同亚群计算的潜在群体倍增时间在4至50天之间。得出的结论是细胞丢失率很高，尤其是颗粒细胞。除细胞丢失外，一个大的非增殖区室导致肿瘤体积倍增时间延迟。以肾腺癌为例的晚期人类肿瘤的增殖异质性对治疗和预后具有重要意义。
