Designing a schedule of progestin administration in the control of endometrial carcinoma growth in the nude mouse model.
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.
Mortel
R
R
Department of Obstetrics and Gynecology, Milton S. Hershey Medical Center, Hershey, PA 17033.
Zaino
R J
RJ
Satyaswaroop
P G
PG
D000818:Animals; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008525:Medroxyprogesterone / Q000008:administration & dosage / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011372:Progestins / Q000008:administration & dosage* / Q000627:therapeutic use; D011980:Receptors, Progesterone / Q000378:metabolism; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure
D011372:Progestins; D011980:Receptors, Progesterone; D008525:Medroxyprogesterone