Abstract | PURPOSE: The purpose of this research was to assess the effects of single agent and combination treatment with trastuzumab and gefitinib on tumor growth and tumor microenvironment in two HER-2/neu overexpressing breast xenograft models, MDA-MB-435/LCC6(HER-2) (LCC6(HER-2); estrogen receptor negative) and MCF-7(HER-2) ( estrogen receptor positive). EXPERIMENTAL DESIGN: LCC6(HER-2) and MCF-7(HER-2) cells, both in tissue culture and xenografts grown in SCID-Rag 2M mice, were treated with trastuzumab and gefitinib, alone or in combination. The rate of tumor growth was determined. In addition, tumor HER-2/neu and epidermal growth factor receptor expression, cell viability, cell cycle distribution, and proportion of viable hypoxic cells were determined by flow cytometric analyses of single tumor cell suspensions. RESULTS: CONCLUSIONS: Although in vivo efficacy studies in two HER-2/neu overexpressing breast xenograft models showed that the combination of trastuzumab and gefitinib was effective, analyses of various cellular parameters failed to reveal beneficial effects and argue that this drug combination may not be favorable.
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Authors | Corinna Warburton, Wieslawa H Dragowska, Karen Gelmon, Stephen Chia, Hong Yan, Dana Masin, Tetyana Denyssevych, Anne E Wallis, Marcel B Bally |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 10
Issue 7
Pg. 2512-24
(Apr 01 2004)
ISSN: 1078-0432 [Print] United States |
PMID | 15073131
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Coloring Agents
- Quinazolines
- Tetrazolium Salts
- Thiazoles
- ErbB Receptors
- Receptor, ErbB-2
- thiazolyl blue
- Trastuzumab
- Gefitinib
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Topics |
- Animals
- Antibodies, Monoclonal
(therapeutic use)
- Antibodies, Monoclonal, Humanized
- Antineoplastic Combined Chemotherapy Protocols
- Breast Neoplasms
(metabolism)
- Cell Cycle
- Cell Line, Tumor
- Cell Membrane
(metabolism)
- Cell Survival
- Coloring Agents
(pharmacology)
- Dose-Response Relationship, Drug
- Down-Regulation
- ErbB Receptors
(biosynthesis)
- Female
- Flow Cytometry
- Gefitinib
- Humans
- Hypoxia
- Mammary Neoplasms, Animal
(drug therapy)
- Mice
- Mice, SCID
- Neoplasm Transplantation
- Phosphorylation
- Quinazolines
(therapeutic use)
- Receptor, ErbB-2
(biosynthesis)
- Subcellular Fractions
(metabolism)
- Tetrazolium Salts
(pharmacology)
- Thiazoles
(pharmacology)
- Time Factors
- Trastuzumab
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