Noble R L
Cancer Res. 1977 Jan;37(1):82-94.
A continuation of previous studies of hormone-dependent tumors in various organs in Nb rats concerns the effects of removal of the hormone stimulus from animals with growing tumors. Tumor regression usually followed this procedure, and in various models it was associated with an increased survival of the animal. A regressed tumor could be caused to grow at any time by estrogen treatment, and the resulting tumor remained hormone dependent, although some progression might occur. Continuous breeding rarely affected the growth or progression of transplanted adrenal or breast carcinomas. When spontaneous regrowth of tumors took place following removal of the estrogen stimulus all types of tumors (except leiomyomas of the uterus, showed progression usually to autonomy, and in the case of male rats bearing breast carcinomas it was inevitable. The substitution of pellets containing a reduced level of estrone to determine which prevented regression and allowed uninterrupted growth offered an assessment of the type or amount of hormone required for the growth of different tumors. By means of such a model of breast cancer in male rats, it was possible to demonstrate that a reduction in hormone levels sufficient to prevent advancing tumor growth, but adequate to reduce the extent of regression, also reduced the frequency or prevented the development of autonomous change. Although regression per se was not a prerequisite for autonomous change, the paradox was evident that progression towards autonomous growth was accelerated with procedures expected to check tumor growth and was minimal with procedures that accelerated it. Liver metastases of hormone-dependent adrenal carcinomas continued growth and could not be influenced by removal of estrogen, although the primary transplant regressed. When such metastases were transplanted, they were not found to have progressed to autonomy but retained a hormone-dependent status. Some tumors, when maintained in estrogen-conditioned hosts, apparently showed a reversion to a more hormone-dependent cell type rather than the expected progression towards autonomy. A theory is suggested to explain the experiments findings on the development and control of estrogen-responsive tumors.
对Nb大鼠各种器官中激素依赖性肿瘤的先前研究的延续涉及从患有生长肿瘤的动物中去除激素刺激的影响。肿瘤消退通常在该程序之后发生，并且在各种模型中，它与动物存活率的提高相关。通过雌激素治疗，消退的肿瘤可在任何时候重新生长，并且由此产生的肿瘤仍然依赖激素，尽管可能会发生一些进展。连续繁殖很少影响移植的肾上腺或乳腺癌的生长或进展。当去除雌激素刺激后肿瘤发生自发再生长时，所有类型的肿瘤（子宫平滑肌瘤除外）通常会进展为自主性，对于患有乳腺癌的雄性大鼠来说，这是不可避免的。用含有降低水平雌酮的药丸进行替代，以确定哪些药丸可防止消退并允许不间断生长，这提供了对不同肿瘤生长所需激素类型或量的评估。通过这种雄性大鼠乳腺癌模型，可以证明激素水平的降低足以防止肿瘤生长进展，但足以减少消退程度，同时也降低了自主性变化的频率或阻止了其发展。尽管消退本身不是自主性变化的先决条件，但矛盾之处显而易见，即预期会抑制肿瘤生长的程序会加速向自主性生长的进展，而加速肿瘤生长的程序则进展最小。激素依赖性肾上腺癌的肝转移继续生长，并且不受雌激素去除的影响，尽管原发性移植瘤会消退。当移植这种转移瘤时，未发现它们已进展为自主性，而是保持激素依赖性状态。一些肿瘤在雌激素预处理的宿主中维持时，显然表现出向更依赖激素的细胞类型的逆转，而不是预期的向自主性的进展。有人提出一种理论来解释关于雌激素反应性肿瘤发展和控制的实验结果。
