| Identification of estrogenic tamoxifen metabolite(s) in tamoxifen-resistant human breast tumors. | |
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MedLine Citation:
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PMID: 1588380 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: We have shown previously that acquired tamoxifen resistance in an in vivo experimental model is associated with reduced tamoxifen accumulation, isomerization of trans-4-hydroxytamoxifen, and tamoxifen-stimulated tumor growth. The purpose of this study is to isolate and verify the presence of estrogenic tamoxifen metabolites in human breast tumors using high-performance liquid chromatography (HPLC) and mass-spectrometry (MS) techniques. PATIENTS AND METHODS: In the present study, we used HPLC and MS to identify the presence of estrogenic metabolites in tumor samples excised from athymic nude mice and in human breast tumors isolated from patients receiving adjuvant tamoxifen therapy. RESULTS: We identified the presence of metabolite E, a known estrogenic metabolite of tamoxifen, in tamoxifen-resistant MCF-7 human breast tumors implanted in athymic nude mice, as well as in tumors from patients with clinical resistance. Additionally, we separated another estrogenic metabolite, bisphenol, by HPLC, and this was also tentatively confirmed by MS analysis. CONCLUSION: These data suggest that cellular tamoxifen metabolism to estrogenic metabolites may in part contribute to stimulating the growth of hormone-responsive breast tumors following prolonged exposure to tamoxifen. Further evaluation of the relationship between cellular metabolism and acquired tamoxifen resistance is warranted. |
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Authors:
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V J Wiebe; C K Osborne; W L McGuire; M W DeGregorio |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of clinical oncology : official journal of the American Society of Clinical Oncology Volume: 10 ISSN: 0732-183X ISO Abbreviation: J. Clin. Oncol. Publication Date: 1992 Jun |
Date Detail:
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Created Date: 1992-06-25 Completed Date: 1992-06-25 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8309333 Medline TA: J Clin Oncol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 990-4 Citation Subset: IM |
Affiliation:
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Cancer Therapy and Research Center, San Antonio, TX. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Breast Neoplasms / chemistry, drug therapy* Chromatography, High Pressure Liquid Drug Resistance Female Humans Mass Spectrometry Mice Mice, Nude Neoplasm Transplantation Tamoxifen / analogs & derivatives*, analysis* |
| Chemical | |
Reg. No./Substance:
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10540-29-1/Tamoxifen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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