IMR Press / FBL / Volume 12 / Issue 6 / DOI: 10.2741/2228

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article
Combination of 4-HPR and oral contraceptive in monkey model of chemoprevention of ovarian cancer
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1 Department of OB/GYN, University of Arizona, College of Medicine, Tucson, AZ 85724, USA
2 University of Arizona, College of Public Health, Tucson, AZ 85724, USA
3 Department of Veterinary Sciences Park, M. D. Anderson Cancer Center, Houston, TX, 77030, USA
4 Gynecologic Oncology, M. D. Anderson Cancer Center, Houston, TX, 77030, USA
Front. Biosci. (Landmark Ed) 2007, 12(6), 2260–2268; https://doi.org/10.2741/2228
Published: 1 January 2007
Abstract

4-(N-hydroxyphenyl) retinamide (4-HPR) and the oral contraceptives (OCP) are currently being used alone, and in combination, for the prevention of ovarian cancer. However, the mechanism of their effects has not been studied. Non-human primate models are ideal for studying the role of these and other drugs for cancer chemoprevention because of the genetic similarity between primates and humans in respect to hormone regulation and menstrual cycle. 4-HPR and OCP were administered to sixteen female adult Macacca mulatta (Rhesus macaques) for three months alone and in combination. Laparotomy was performed before and after treatment, and ovarian biopsies were obtained to evaluate the expression of retinoid and hormone receptors, and apoptosis.  ERα was undetectable, but ERβ, PR, RXRα, and RXRγ were constitutively expressed in the ovaries. 4-HPR induced RXRα and RXRγ expression at a low level and, OCP induced expression of ERβ. However, the combination of 4-HPR with OCP had a larger effect on expression of retinoid receptors. Apoptosis was detected in the 4-HPR group (equivalent dose: 200 mg/day).

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