A bioassay for antiestrogenic activity - potential utility in drug development and monitoring effective in vivo dosing

Michael DeGregorio, Gregory Wurz, Vernon Emshoff, Steven Koester, Patrick Minor, Valerie Wiebe

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Monitoring effective antiestrogenic activity of the triphenylethylenes in patients with breast cancer is usually determined by the duration of response. The pharmacokinetics of toremifene and tamoxifen have been shown to be highly variable but patient specific. In the present study, we developed a method to accurately assess the antiestrogenic activity of these agents using plasma specimens, cell culture, and cell cycle measurements. Plasma specimens (4-5mls) obtained from patients receiving toremifene (360mg/day for 5 days in a phase I trial) or tamoxifen (20mg/day) were extracted and reconstituted in tissue culture media (4-5mls), and growth inhibition was determined in estrogen responsive MCF-7 cells. Additionally, plasma specimens were quantified for toremifene or tamoxifen concentrations using HPLC. Growth inhibition of plasma specimens containing either toremifene or tamoxifen and their metabolites was also examined. Cell cycle measurements were determined following in vitro exposure with flow cytometric techniques. Our results show that a dose-response relationship exists between cell growth inhibition and cell cycle measurements for human plasma with added toremifene or tamoxifen, and also for human plasma specimens containing drug and its metabolites after treatment. Our antiestrogenic bioassay can address clinical research problems such as patient-specific pharmacokinetics, dosing compliance, and acquired antiestrogen resistance.

Original languageEnglish (US)
Pages (from-to)35-41
Number of pages7
JournalBreast Cancer Research and Treatment
Volume24
Issue number1
DOIs
StatePublished - Feb 1992
Externally publishedYes

Fingerprint

Toremifene
Drug Monitoring
Tamoxifen
Biological Assay
Cell Cycle
Growth
Pharmacokinetics
Estrogen Receptor Modulators
MCF-7 Cells
Plasma Cells
Compliance
Culture Media
Estrogens
Cell Culture Techniques
High Pressure Liquid Chromatography
Breast Neoplasms
Research
Pharmaceutical Preparations

Keywords

  • antiestrogens
  • bioassay
  • tamoxifen
  • toremifene

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A bioassay for antiestrogenic activity - potential utility in drug development and monitoring effective in vivo dosing. / DeGregorio, Michael; Wurz, Gregory; Emshoff, Vernon; Koester, Steven; Minor, Patrick; Wiebe, Valerie.

In: Breast Cancer Research and Treatment, Vol. 24, No. 1, 02.1992, p. 35-41.

Research output: Contribution to journalArticle

DeGregorio, Michael ; Wurz, Gregory ; Emshoff, Vernon ; Koester, Steven ; Minor, Patrick ; Wiebe, Valerie. / A bioassay for antiestrogenic activity - potential utility in drug development and monitoring effective in vivo dosing. In: Breast Cancer Research and Treatment. 1992 ; Vol. 24, No. 1. pp. 35-41.
@article{3ec133ee9c1240008967124a206c9fc9,
title = "A bioassay for antiestrogenic activity - potential utility in drug development and monitoring effective in vivo dosing",
abstract = "Monitoring effective antiestrogenic activity of the triphenylethylenes in patients with breast cancer is usually determined by the duration of response. The pharmacokinetics of toremifene and tamoxifen have been shown to be highly variable but patient specific. In the present study, we developed a method to accurately assess the antiestrogenic activity of these agents using plasma specimens, cell culture, and cell cycle measurements. Plasma specimens (4-5mls) obtained from patients receiving toremifene (360mg/day for 5 days in a phase I trial) or tamoxifen (20mg/day) were extracted and reconstituted in tissue culture media (4-5mls), and growth inhibition was determined in estrogen responsive MCF-7 cells. Additionally, plasma specimens were quantified for toremifene or tamoxifen concentrations using HPLC. Growth inhibition of plasma specimens containing either toremifene or tamoxifen and their metabolites was also examined. Cell cycle measurements were determined following in vitro exposure with flow cytometric techniques. Our results show that a dose-response relationship exists between cell growth inhibition and cell cycle measurements for human plasma with added toremifene or tamoxifen, and also for human plasma specimens containing drug and its metabolites after treatment. Our antiestrogenic bioassay can address clinical research problems such as patient-specific pharmacokinetics, dosing compliance, and acquired antiestrogen resistance.",
keywords = "antiestrogens, bioassay, tamoxifen, toremifene",
author = "Michael DeGregorio and Gregory Wurz and Vernon Emshoff and Steven Koester and Patrick Minor and Valerie Wiebe",
year = "1992",
month = "2",
doi = "10.1007/BF01832356",
language = "English (US)",
volume = "24",
pages = "35--41",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",
number = "1",

}

TY - JOUR

T1 - A bioassay for antiestrogenic activity - potential utility in drug development and monitoring effective in vivo dosing

AU - DeGregorio, Michael

AU - Wurz, Gregory

AU - Emshoff, Vernon

AU - Koester, Steven

AU - Minor, Patrick

AU - Wiebe, Valerie

PY - 1992/2

Y1 - 1992/2

N2 - Monitoring effective antiestrogenic activity of the triphenylethylenes in patients with breast cancer is usually determined by the duration of response. The pharmacokinetics of toremifene and tamoxifen have been shown to be highly variable but patient specific. In the present study, we developed a method to accurately assess the antiestrogenic activity of these agents using plasma specimens, cell culture, and cell cycle measurements. Plasma specimens (4-5mls) obtained from patients receiving toremifene (360mg/day for 5 days in a phase I trial) or tamoxifen (20mg/day) were extracted and reconstituted in tissue culture media (4-5mls), and growth inhibition was determined in estrogen responsive MCF-7 cells. Additionally, plasma specimens were quantified for toremifene or tamoxifen concentrations using HPLC. Growth inhibition of plasma specimens containing either toremifene or tamoxifen and their metabolites was also examined. Cell cycle measurements were determined following in vitro exposure with flow cytometric techniques. Our results show that a dose-response relationship exists between cell growth inhibition and cell cycle measurements for human plasma with added toremifene or tamoxifen, and also for human plasma specimens containing drug and its metabolites after treatment. Our antiestrogenic bioassay can address clinical research problems such as patient-specific pharmacokinetics, dosing compliance, and acquired antiestrogen resistance.

AB - Monitoring effective antiestrogenic activity of the triphenylethylenes in patients with breast cancer is usually determined by the duration of response. The pharmacokinetics of toremifene and tamoxifen have been shown to be highly variable but patient specific. In the present study, we developed a method to accurately assess the antiestrogenic activity of these agents using plasma specimens, cell culture, and cell cycle measurements. Plasma specimens (4-5mls) obtained from patients receiving toremifene (360mg/day for 5 days in a phase I trial) or tamoxifen (20mg/day) were extracted and reconstituted in tissue culture media (4-5mls), and growth inhibition was determined in estrogen responsive MCF-7 cells. Additionally, plasma specimens were quantified for toremifene or tamoxifen concentrations using HPLC. Growth inhibition of plasma specimens containing either toremifene or tamoxifen and their metabolites was also examined. Cell cycle measurements were determined following in vitro exposure with flow cytometric techniques. Our results show that a dose-response relationship exists between cell growth inhibition and cell cycle measurements for human plasma with added toremifene or tamoxifen, and also for human plasma specimens containing drug and its metabolites after treatment. Our antiestrogenic bioassay can address clinical research problems such as patient-specific pharmacokinetics, dosing compliance, and acquired antiestrogen resistance.

KW - antiestrogens

KW - bioassay

KW - tamoxifen

KW - toremifene

UR - http://www.scopus.com/inward/record.url?scp=0027056663&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027056663&partnerID=8YFLogxK

U2 - 10.1007/BF01832356

DO - 10.1007/BF01832356

M3 - Article

C2 - 1463870

AN - SCOPUS:0027056663

VL - 24

SP - 35

EP - 41

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 1

ER -