Biomarker modulation in a nonhuman rhesus primate model for ovarian cancerchemoprevention

Objective: The objective of this study was to explore whether a nonhuman pr imate model Could be developed to test drugs for the prevention of ovarian cancer. Methods: Nineteen adult female Rhesus macaques were given fenretinide (4HPR ), oral contraceptives (OCP), the combination (4HPR + OCP), or no medicatio n for 3 months. Exploratory laparotomy was done pre- and postdrug to assess intermediary biomarkers of neoplastic phenotype, proliferation, response p athways, and growth-regulatory and metabolic markers. Fluorescence emission spectra were plotted for each group pre- and postdrug and means were overl aid on these plots and normalized. Fluorescence intensities were compared u sing the 2-tailed Student t test, (P = 0.1-0.01). Results: All monkeys tolerated drugs and surgeries without difficulty. Hist ochemical markers showed no significant trend. However, fluorescence spectr oscopy showed increased intensity at 450 nm excitation, 550 unit emission c orrelating with increased FAD presence. The 4HPR group (P = 0.01) showed hi gher intensity than the OCP group (P = 0.05-0.07) when compared with the co ntrols. Decreased emission was seen at 350 unit excitation, 450 nm emission correlating with decreased NAD(P)H presence. The OCP group showed the larg est change (P < 0.01), and the control group showed the smallest change. Conclusions: The nonhuman primate is an excellent model to test drug effect on the ovarian surface epithelium and merits additional study. Fluorescenc e spectroscopy was the most sensitive marker for drug activity and the appa rent increase in NAD and FAD in the 4HPR group is consistent with the effec t of 4HPR observed in cell culture. The differences between the OCP and the 4HPR groups suggest a different mechanism of activity of these drugs.