A bioassay for antiestrogenic activity — potential utility in drug development and monitoring effectivein vivo dosing
| Autor: | Koester Sk, Patrick Minor, Valerie J. Wiebe, Vernon Emshoff, DeGregorio Mw, Gregory Wurz |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Cancer Research
medicine.medical_specialty medicine.drug_class Breast Neoplasms chemistry.chemical_compound Pharmacokinetics In vivo Internal medicine Tumor Cells Cultured medicine Humans Bioassay Toremifene skin and connective tissue diseases Chromatography High Pressure Liquid Dose-Response Relationship Drug business.industry Estrogen Antagonists Flow Cytometry Antiestrogen Tamoxifen Endocrinology Oncology chemistry Estrogen Female Drug Screening Assays Antitumor Growth inhibition business Cell Division hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Breast Cancer Research and Treatment. 24:35-41 |
| ISSN: | 1573-7217 0167-6806 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink