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Reproductive System and Mammary Gland
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Justin D. Vidal, Charles E. Wood, Karyn Colman, Katharine M. Whitney, Dianne M. Creasy
A variety of other proliferative changes can be identified in the ovary including rete hyperplasia/adenoma, hemangioma, fibroma, and mesothelioma. Fibromas, an unusual tumor-type in the canine ovary, have been seen with an increased incidence in old dogs given mibolerone (a non-progestational androgenic steroid) for over 9 years at efficacious doses, though not at suprapharmacologic doses (Seaman 1985). The tumors were observed as single or multiple firm, rounded and sometimes bilateral, nodular masses in the medulla or hilar region of the ovary. In addition, proliferative changes have been identified in the smooth muscle extending from the hilus of the ovary into the mesovarium and rats treated with various β-receptor agonists have developed mesovarial leiomyomas (Gopinath and Gibson 1987; Jack et al. 1983).
Darolutamide in hormone-sensitive and castration-resistant prostate cancer
Published in Expert Review of Clinical Pharmacology, 2021
Valeria Emma Palmieri, Giandomenico Roviello, Alberto D’Angelo, Chiara Casadei, Ugo De Giorgi, Roberta Giorgione
Normally, antiandrogens block the negative hypothalamic-pituitary-gonadal feedback which, in turn, inhibits the release of luteinizing hormone-releasing hormone (LH-RH) in presence of testosterone: as a result, serum testosterone level increases and competes for ARs binding [26]. In in vivo test, darolutamide has reported poor permeability through the blood-brain barrier (BBB), with a significant lower brain/serum ratio than enzalutamide and apalutamide (1.9–3.9%, 27%, and 62%, respectively), no consequent substantial effect on the hypothalamic-pituitary-gonadal axis and a lower risk of seizures. In castration-resistant prostate cancer (CRPC) mouse model, darolutamide did not increase testosterone levels and significantly inhibited tumor growth compared to enzalutamide. When tested on cell lines derived from bone metastases of CRPC patients (VCaP cell) with overexpressed AR, in presence of a synthetic androgen (mibolerone), ODM-201 and ORM-15,341 have been shown to suppress androgen-induced proliferation more effectively than enzalutamide and apalutamide [22].