Influence of the interval between primary tumor removal and chemotherapy on kinetics and growth of metastases.
Influence of the interval between primary tumor removal and chemotherapy on kinetics and growth of metastases.
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发表时间：
1983-04
期刊：
影响因子：
11.2
通讯作者：
B. Fisher;N. Gunduz;E. Saffer
中科院分区：
文献类型：
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作者：
B. Fisher;N. Gunduz;E. Saffer
在许多动物模型中，原发性肿瘤的切除会导致转移灶中细胞的增殖增加。目前使用小鼠乳腺肿瘤进行的研究是为了确定原发肿瘤切除和单剂量环磷酰胺（CY）给药之间的时间间隔的变化如何影响残留肿瘤细胞的标记指数、它们的生长和动物存活。肿瘤切除当天给予CY（240 mg/kg）比3天后（转移瘤标记指数（LI）达到峰值时）的效果更佳。如果在原发性肿瘤切除后 7 天给药，此时 LI 已恢复至术前水平，则效果最差。手术前给予 CY 时效果最大。它完全阻止了因肿瘤切除而导致的LI增加，更有效地抑制了残留肿瘤的生长，并且比任何其他情况下都更大程度地延长了生存期。肿瘤切除和给予相对少量 CY (60 mg/kg) 之间的时间间隔至关重要。当在肿瘤切除当天给予时，残余病灶的 LI 增加，这比肿瘤切除后的增加更大。当肿瘤切除后 3 天给药时，较小剂量在抑制 LI 方面几乎与较大剂量一样有效。从动力学的角度来看，在使用化疗之前减少肿瘤负荷没有优势。该模型中的肿瘤反应表明，为了最有效地控制转移，最好在原发肿瘤切除时或之前使用最大耐受剂量的化疗。该结果为围手术期辅助化疗的使用提供了生物学原理。
In many animal models, primary tumor removal produces increased proliferation of cells in metastatic foci. The present investigations using a murine mammary tumor were carried out to determine how a variation in the time interval between primary tumor removal and administration of a single dose of cyclophosphamide (CY) affected labeling indices of residual tumor cells, their growth, and animal survival. The CY (240 mg/kg) had a more favorable effect when given on the day of tumor removal than 3 days after, a time when the labeling index (LI) of metastases was at a peak. It was least effective if given at 7 days following primary tumor excision, when the LI had returned to the preoperative level. The greatest effect occurred when the CY was given prior to operation. It completely prevented the increase in LI resulting from tumor removal, more effectively suppressed the growth of residual tumor, and prolonged survival to a greater extent than was noted under any other circumstance. The interval between tumor removal and administration of a relatively small amount of CY (60 mg/kg) was critical. When given on the day of tumor removal, an increase in LI of the residual focus occurred which was greater than that occurring as a result of tumor removal. When given 3 days after tumor removal, the smaller dose was almost as effective in suppressing LI as was the larger. From a kinetic standpoint, there was no advantage in reducing the tumor burden prior to the use of chemotherapy. The tumor response in this model suggests that, for the most effective control of metastases, the largest tolerable dose of chemotherapy would best be used at the time of or before primary tumor removal. The results provide a biological rationale for the use of perioperative adjuvant chemotherapy.