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  • Title: Potent inhibitory activity of a new antiestrogen, RU 16 117, on the development and growth of DMBA-induced rat mammary adenocarcinoma.
    Author: Labrie F, Kelly PA, Asselin J, Raynaud JP.
    Journal: Recent Results Cancer Res; 1976; (57):109-20. PubMed ID: 827798.
    Abstract:
    When initiated the same day as dimethylbenzanthracene (DMBA) administration, daily treatment with 8 or 24 mug of the new antiestrogen RU 16117 (11alpha-methoxy ethinyl estradiol) completely prevented the appearance of mammary tumors in all animals up to the last time interval studied (130 days after DMBA administration). At daily doses of 0.5 and 2.0 mug of RU 16117, the tumor incidence was reduced to 78.6% and 40.0%, respectively. The levels of receptors for estradiol, progesterone, and prolactin in tumor tissue were reduced after treatment with 2.0 mug RU 16117 while the binding of growth hormone and insulin was not affected. While plasma LH levels were decreased after treatment with 8 or 24 mug RU 16117, plasma prolactin levels were slightly increased in animals receiving the highest dose of the antiestrogen. When RU 16117 was given at the daily dose of 24 mug for a period of 4 weeks, RU 16117 led to 65% reduction of the number of already established DMBA-induced mammary tumors. Not only the tumor number but also the tumor size was reduced by RU 16117 in a manner similar to that following ovariectomy. That the inhibitory effect of RU 16117 was not due to its low estrogenic activity is indicated by the absence of inhibitory effect of similar treatment with a range of doses (0.1-12.5 mug per day) of estradiol-17beta which cover the low estrogenic activity of the doses of RU 16117 used. Decreased levels of receptors for estradiol-17beta, progesterone, and prolactin were found in the tumors remaining after ovariectomy while treatment with the dose (24 mug) of RU 16117, efficient to inhibit tumor growth, has a similar inhibitory effect on the levels of estradiol-17beta and prolactin receptors. The present data indicate that the potent inhibitory effect of RU 16117 on the development and growth of DMBA-induced mammary tumors results from actions at both the hypothalamic-pituitary and tumor levels. The action at the peripheral level would be possibly secondary to a reduced sensitivity of the tissue to circulating hormones through lowering of hormone receptor concentrations.
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