Van Dierendonck J H, Keijzer R, Cornelisse C J, Van de Velde C J
Department of Surgery, University Hospital Leiden, The Netherlands.
Cancer. 1991 Aug 15;68(4):759-67. doi: 10.1002/1097-0142(19910815)68:4<759::aid-cncr2820680417>3.0.co;2-2.
The effect of surgical removal of "primary" tumors on the cytokinetics of local tumor remnants, secondary implants, and metastases was investigated in three different rat tumor models in the Wag/Rij rat: a slow-growing (MCR83) and a fast-growing (EMR86) hormone-dependent mammary tumor and a rapidly, but autonomously growing carcinoma (MCR86). The latter two tumors had metastatic potential. Cell kinetic studies were done using in vivo labeling with 5'-bromodeoxyuridine (BrdUrd). Thirty-three hours after removal of a subcutaneous MCR83 flank tumor, secondary implants showed a significant (P less than 0.05) but transient increase in the BrdUrd labeling index (LI). A more rapid and prolonged increase, lasting for at least 7 days, was observed in EMR86 lymph node and lung metastases. In both models, no effect was observed after sham surgery (consisting of opening and closing of the skin under anesthesia). Removal of MCR86 tumors (growing in the hind leg muscle) also resulted in a rapid, transient LI increase in metastases. Continuous BrdUrd labeling experiments in this tumor model did not favor the hypothesis that the LI increase predominantly resulted from an increase in the growth fraction. Moreover, in this model, the effect was related to operation trauma. A similar increase in LI, although smaller than after tumor removal, was seen after major surgical trauma in MCR83 flank tumors. These results indicate that in the rat, tumor removal and/or major surgical trauma may modulate the cytokinetics of distant metastases significantly. A study of the systemic, possibly endocrine, factors involved in the growth-stimulating effect of surgical trauma in these rat tumor models may help to assess the clinical relevance of these findings for patients with breast cancer.
在Wag/Rij大鼠的三种不同大鼠肿瘤模型中，研究了手术切除“原发性”肿瘤对局部肿瘤残余、继发性植入物和转移灶细胞动力学的影响：一种生长缓慢的（MCR83）和一种生长快速的（EMR86）激素依赖性乳腺肿瘤，以及一种快速但自主生长的癌（MCR86）。后两种肿瘤具有转移潜能。使用5'-溴脱氧尿苷（BrdUrd）进行体内标记进行细胞动力学研究。切除皮下MCR83侧腹肿瘤33小时后，继发性植入物的BrdUrd标记指数（LI）出现显著（P<0.05）但短暂的增加。在EMR86淋巴结和肺转移灶中观察到更快速和持久的增加，持续至少7天。在这两种模型中，假手术（包括在麻醉下打开和关闭皮肤）后未观察到效果。切除MCR86肿瘤（在后腿肌肉中生长）也导致转移灶中LI快速、短暂增加。在该肿瘤模型中进行的连续BrdUrd标记实验不支持LI增加主要源于生长分数增加这一假设。此外，在该模型中，这种影响与手术创伤有关。在MCR83侧腹肿瘤进行重大手术创伤后，观察到LI有类似增加，尽管比切除肿瘤后小。这些结果表明，在大鼠中，肿瘤切除和/或重大手术创伤可能显著调节远处转移灶的细胞动力学。对这些大鼠肿瘤模型中手术创伤的生长刺激作用所涉及的全身因素（可能是内分泌因素）进行研究，可能有助于评估这些发现对乳腺癌患者的临床相关性。
