Biomarker modulation in a nonhuman rhesus primate model for ovarian cancer chemoprevention

Molly Brewer, Urs Utzinger, William Satterfield, Lori Hill, David Gershenson, Robert Bast, J. Taylor Wharton, Rebecca Richards-Kortum, Michele Follen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objective: The objective of this study was to explore whether a nonhuman primate 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 medication for 3 months. Exploratory laparotomy was done pre- and postdrug to assess intermediary biomarkers of neoplastic phenotype, proliferation, response pathways, and growth-regulatory and metabolic markers. Fluorescence emission spectra were plotted for each group pre- and postdrug and means were overlaid on these plots and normalized. Fluorescence intensities were compared using the 2-tailed Student t test, (P = 0.1-0.01). Results: All monkeys tolerated drugs and surgeries without difficulty. Histochemical markers showed no significant trend. However, fluorescence spectroscopy showed increased intensity at 450 nm excitation, 550 nm emission correlating with increased FAD presence. The 4HPR group (P = 0.01) showed higher intensity than the OCP group (P = 0.05-0.07) when compared with the controls. Decreased emission was seen at 350 nm excitation, 450 nm emission correlating with decreased NAD(P)H presence. The OCP group showed the largest 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. Fluorescence spectroscopy was the most sensitive marker for drug activity and the apparent increase in NAD and FAD in the 4HPR group is consistent with the effect of 4HPR observed in cell culture. The differences between the OCP and the 4HPR groups suggest a different mechanism of activity of these drugs.

Original languageEnglish (US)
Pages (from-to)889-893
Number of pages5
JournalCancer Epidemiology Biomarkers and Prevention
Volume10
Issue number8
StatePublished - Jan 1 2001

Fingerprint

Chemoprevention
Oral Contraceptives
Ovarian Neoplasms
Primates
Biomarkers
Flavin-Adenine Dinucleotide
Pharmaceutical Preparations
Fluorescence Spectrometry
NAD
Fluorescence
Fenretinide
Macaca mulatta
Laparotomy
Haplorhini
Epithelium
Cell Culture Techniques
Students
Phenotype
Control Groups
Growth

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Biomarker modulation in a nonhuman rhesus primate model for ovarian cancer chemoprevention. / Brewer, Molly; Utzinger, Urs; Satterfield, William; Hill, Lori; Gershenson, David; Bast, Robert; Wharton, J. Taylor; Richards-Kortum, Rebecca; Follen, Michele.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 10, No. 8, 01.01.2001, p. 889-893.

Research output: Contribution to journalArticle

Brewer, M, Utzinger, U, Satterfield, W, Hill, L, Gershenson, D, Bast, R, Wharton, JT, Richards-Kortum, R & Follen, M 2001, 'Biomarker modulation in a nonhuman rhesus primate model for ovarian cancer chemoprevention', Cancer Epidemiology Biomarkers and Prevention, vol. 10, no. 8, pp. 889-893.
Brewer, Molly ; Utzinger, Urs ; Satterfield, William ; Hill, Lori ; Gershenson, David ; Bast, Robert ; Wharton, J. Taylor ; Richards-Kortum, Rebecca ; Follen, Michele. / Biomarker modulation in a nonhuman rhesus primate model for ovarian cancer chemoprevention. In: Cancer Epidemiology Biomarkers and Prevention. 2001 ; Vol. 10, No. 8. pp. 889-893.
@article{ec552be709dc4353a29f0eaf50c0c6bc,
title = "Biomarker modulation in a nonhuman rhesus primate model for ovarian cancer chemoprevention",
abstract = "Objective: The objective of this study was to explore whether a nonhuman primate 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 medication for 3 months. Exploratory laparotomy was done pre- and postdrug to assess intermediary biomarkers of neoplastic phenotype, proliferation, response pathways, and growth-regulatory and metabolic markers. Fluorescence emission spectra were plotted for each group pre- and postdrug and means were overlaid on these plots and normalized. Fluorescence intensities were compared using the 2-tailed Student t test, (P = 0.1-0.01). Results: All monkeys tolerated drugs and surgeries without difficulty. Histochemical markers showed no significant trend. However, fluorescence spectroscopy showed increased intensity at 450 nm excitation, 550 nm emission correlating with increased FAD presence. The 4HPR group (P = 0.01) showed higher intensity than the OCP group (P = 0.05-0.07) when compared with the controls. Decreased emission was seen at 350 nm excitation, 450 nm emission correlating with decreased NAD(P)H presence. The OCP group showed the largest 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. Fluorescence spectroscopy was the most sensitive marker for drug activity and the apparent increase in NAD and FAD in the 4HPR group is consistent with the effect of 4HPR observed in cell culture. The differences between the OCP and the 4HPR groups suggest a different mechanism of activity of these drugs.",
author = "Molly Brewer and Urs Utzinger and William Satterfield and Lori Hill and David Gershenson and Robert Bast and Wharton, {J. Taylor} and Rebecca Richards-Kortum and Michele Follen",
year = "2001",
month = "1",
day = "1",
language = "English (US)",
volume = "10",
pages = "889--893",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research Inc.",
number = "8",

}

TY - JOUR

T1 - Biomarker modulation in a nonhuman rhesus primate model for ovarian cancer chemoprevention

AU - Brewer, Molly

AU - Utzinger, Urs

AU - Satterfield, William

AU - Hill, Lori

AU - Gershenson, David

AU - Bast, Robert

AU - Wharton, J. Taylor

AU - Richards-Kortum, Rebecca

AU - Follen, Michele

PY - 2001/1/1

Y1 - 2001/1/1

N2 - Objective: The objective of this study was to explore whether a nonhuman primate 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 medication for 3 months. Exploratory laparotomy was done pre- and postdrug to assess intermediary biomarkers of neoplastic phenotype, proliferation, response pathways, and growth-regulatory and metabolic markers. Fluorescence emission spectra were plotted for each group pre- and postdrug and means were overlaid on these plots and normalized. Fluorescence intensities were compared using the 2-tailed Student t test, (P = 0.1-0.01). Results: All monkeys tolerated drugs and surgeries without difficulty. Histochemical markers showed no significant trend. However, fluorescence spectroscopy showed increased intensity at 450 nm excitation, 550 nm emission correlating with increased FAD presence. The 4HPR group (P = 0.01) showed higher intensity than the OCP group (P = 0.05-0.07) when compared with the controls. Decreased emission was seen at 350 nm excitation, 450 nm emission correlating with decreased NAD(P)H presence. The OCP group showed the largest 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. Fluorescence spectroscopy was the most sensitive marker for drug activity and the apparent increase in NAD and FAD in the 4HPR group is consistent with the effect of 4HPR observed in cell culture. The differences between the OCP and the 4HPR groups suggest a different mechanism of activity of these drugs.

AB - Objective: The objective of this study was to explore whether a nonhuman primate 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 medication for 3 months. Exploratory laparotomy was done pre- and postdrug to assess intermediary biomarkers of neoplastic phenotype, proliferation, response pathways, and growth-regulatory and metabolic markers. Fluorescence emission spectra were plotted for each group pre- and postdrug and means were overlaid on these plots and normalized. Fluorescence intensities were compared using the 2-tailed Student t test, (P = 0.1-0.01). Results: All monkeys tolerated drugs and surgeries without difficulty. Histochemical markers showed no significant trend. However, fluorescence spectroscopy showed increased intensity at 450 nm excitation, 550 nm emission correlating with increased FAD presence. The 4HPR group (P = 0.01) showed higher intensity than the OCP group (P = 0.05-0.07) when compared with the controls. Decreased emission was seen at 350 nm excitation, 450 nm emission correlating with decreased NAD(P)H presence. The OCP group showed the largest 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. Fluorescence spectroscopy was the most sensitive marker for drug activity and the apparent increase in NAD and FAD in the 4HPR group is consistent with the effect of 4HPR observed in cell culture. The differences between the OCP and the 4HPR groups suggest a different mechanism of activity of these drugs.

UR - http://www.scopus.com/inward/record.url?scp=0034902134&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034902134&partnerID=8YFLogxK

M3 - Article

C2 - 11489756

AN - SCOPUS:0034902134

VL - 10

SP - 889

EP - 893

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 8

ER -