Document Detail

Sequential combination chemotherapy in human breast cancer: a basis for increased antineoplastic activity and bone marrow protection.
MedLine Citation:
PMID:  17531145     Owner:  NLM     Status:  MEDLINE    
These studies were designed to develop procedures that would capitalize on the growth inhibitory effects of tamoxifen (Tam) and methotrexate (MTX) in breast cancer, while protecting bone marrow with a priming dose of 5-fluorouracil (5-FU). High-dose MTX (10 microM) cytotoxicity is maintained in MCF-7 breast cancer cells but reduced in human bone marrow by a priming and nontoxic dose of 5-FU (10 microM). MTX cytotoxicity is decreased in MCF-7 breast cancer cells when the selective estrogen receptor modulator (SERM) Tam (10 microM) is administered 24 hours prior to 5-FU (10 microM) followed two hours later by MTX (early Tam) resulting in a growth rate of 57.42 +/- 4.38% of the control rate. However, when breast cancer cells are exposed to Tam 24 hours after 5-FU + MTX (late Tam), the interaction between MTX and Tam is not antagonistic, the percentage of the control is 29.47 +/- 4.54%. Bone marrow exposure to these drug combinations exhibits a protective effect to the MTX cytotoxicity, with the early Tam combination yielding 59.45 +/- 16.38% of the control for MTX alone. These studies suggest that a) Tam in combination with a priming dose of 5-FU protects bone marrow from MTX cytotoxicity, b) the interactions between Tam and MTX are sequence-dependent, c) Tam decreases the effect of MTX when Tam administration precedes MTX.
J H Davis; J A Desoto; E B Fryar; W M Southerland; D Bowen
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2007-05-15
Journal Detail:
Title:  Cellular and molecular biology (Noisy-le-Grand, France)     Volume:  53     ISSN:  1165-158X     ISO Abbreviation:  Cell. Mol. Biol. (Noisy-le-grand)     Publication Date:  2007  
Date Detail:
Created Date:  2007-05-28     Completed Date:  2008-01-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9216789     Medline TA:  Cell Mol Biol (Noisy-le-grand)     Country:  France    
Other Details:
Languages:  eng     Pagination:  18-26     Citation Subset:  IM    
1Hampton University, School of Pharmacy, Hampton, VA 23668, USA.
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MeSH Terms
Antimetabolites, Antineoplastic / administration & dosage
Antineoplastic Agents, Hormonal / administration & dosage
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Blotting, Western
Bone Marrow Cells / drug effects
Breast Neoplasms / drug therapy*
Cell Line, Tumor
Cell Survival / drug effects
Flow Cytometry
Fluorouracil / administration & dosage,  pharmacology
Methotrexate / administration & dosage
Tamoxifen / administration & dosage,  pharmacology
Grant Support
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 0/Antineoplastic Agents, Hormonal; 10540-29-1/Tamoxifen; 51-21-8/Fluorouracil; 59-05-2/Methotrexate

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