Mortel R, Zaino R J, Satyaswaroop P G
Department of Obstetrics and Gynecology, Milton S. Hershey Medical Center, Hershey, PA 17033.
Am J Obstet Gynecol. 1990 Apr;162(4):928-34; discussion 934-6. doi: 10.1016/0002-9378(90)91293-l.
We previously showed that combined treatment with tamoxifen and progestin was effective in arresting the growth of human endometrial carcinomas in the nude mouse model. After a 15- to 20-week tumoristatic period, the tumors began to regrow, reminiscent of the clinical situation. Lack of progestin sensitivity during the regrowth period appeared to reflect the absence of progesterone receptor. To test the prediction that intermittent progestin administration may circumvent the regrowth phenomenon, the effect of various doses of progestin on blood progestin levels, EnCa 101 tumor progesterone receptor profiles, and rate of tumor growth were examined. Whereas 1 mg progestin was ineffective in totally down-regulating tumor progesterone receptor, 2 and 5 mg doses resulted in the total disappearance of tumor progesterone receptor by 1 week followed by its reappearance at 5 to 6 weeks and 9 to 10 weeks, respectively. On the basis of these results we predict that intermittent progestin administration may result in better control of endometrial cancer growth in the nude mouse system.
我们之前的研究表明，在裸鼠模型中，他莫昔芬与孕激素联合治疗能有效抑制人子宫内膜癌的生长。经过15至20周的肿瘤静止期后，肿瘤开始重新生长，这与临床情况相似。肿瘤重新生长期间缺乏孕激素敏感性似乎反映了孕激素受体的缺失。为了验证间歇性给予孕激素可能规避肿瘤重新生长现象这一预测，我们研究了不同剂量的孕激素对血液中孕激素水平、EnCa 101肿瘤孕激素受体情况以及肿瘤生长速率的影响。虽然1毫克孕激素无法完全下调肿瘤孕激素受体，但2毫克和5毫克剂量的孕激素分别在1周时使肿瘤孕激素受体完全消失，随后在5至6周和9至10周时再次出现。基于这些结果，我们预测间歇性给予孕激素可能会更好地控制裸鼠系统中子宫内膜癌的生长。
