Source:http://linkedlifedata.com/resource/pubmed/id/11759828
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2001-12-10
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| pubmed:abstractText |
Available clinical and experimental data on the effect of HER-2/neu overexpression on chemosensitivity are controversial. It was the purpose of this in vitro study to define the association between HER-2/neu overexpression and the sensitivity to the chemotherapeutic drug combinations of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) and 5-fluorouracil, epirubicin and cyclophosphamide (FEC) of breast cancer cells derived from 140 chemotherapy-naïve patients at the time of primary surgery. Both drug combinations were tested at six different concentrations ranging from 6.25-200% peak plasma concentration (PPC). Immunohistochemical detection of HER-2/neu overexpression was performed with the HER-2/neu antibodies, CB11, TAB250 and AO485, in the same tumor specimens. Immunoreactions were determined as negative (0/1+), weakly positive (2+) and strongly positive (3+). However, the antibodies varied in their degrees of sensitivity. Breast cancer samples with strong (3+) HER-2/neu overexpression demonstrated 90% growth inhibition (IC90) at significantly lower PPC values, using the CB11 (p = 0.048), TAB250 (p = 0.007) and AO485 (p < or =0.01) antibodies, and showed 50% growth inhibition (IC50) at significantly lower PPC values, using the CB11 antibody (p = 0.01) compared to their counterparts with lower levels of HER-2/neu expression. When analyzing the group of patients with intermediate and strong HER-2/neu overexpression (2+ and 3+), an association between HER-2/neu overexpression and increased chemosensitivity was seen with the TAB250 (p = 0.044) and AO485 (p = 0.032) antibodies, but not with the CB11 antibody (p =0.8) at the IC90 level. Differences in chemosensitivity between samples with strong HER-2/neu overexpression and those with lower levels were then analyzed separately for CMF and FEC. Both regimens achieved 90% tumor growth inhibition at lower PPC values in samples with strong HER-2/neu overexpression (3+) compared to their counterparts with lower expression levels (AO485 p = 0.011 for CMF, and p = 0.09 for FEC). Cumulative concentration-response plots of tumors responding in vitro with 90% tumor cell inhibition showed a stronger dose dependence for both CMF and FEC among tumor samples with strong HER-2/neu overexpression compared to those with lower levels of expression. In conclusion, the data show that HER-2/neu overexpression was not associated with in vitro drug resistance to CMF or FEC. In contrast, tumors with strong HER-2/neu overexpression demonstrated increased dose-dependent in vitro sensitivity to both the FEC and CMF regimens.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclophosphamide,
http://linkedlifedata.com/resource/pubmed/chemical/Epirubicin,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorouracil,
http://linkedlifedata.com/resource/pubmed/chemical/Methotrexate,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
0167-6806
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
69
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
53-63
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:11759828-Adult,
pubmed-meshheading:11759828-Aged,
pubmed-meshheading:11759828-Aged, 80 and over,
pubmed-meshheading:11759828-Antineoplastic Combined Chemotherapy Protocols,
pubmed-meshheading:11759828-Breast Neoplasms,
pubmed-meshheading:11759828-Cyclophosphamide,
pubmed-meshheading:11759828-Dose-Response Relationship, Drug,
pubmed-meshheading:11759828-Drug Resistance, Neoplasm,
pubmed-meshheading:11759828-Drug Screening Assays, Antitumor,
pubmed-meshheading:11759828-Epirubicin,
pubmed-meshheading:11759828-Female,
pubmed-meshheading:11759828-Fluorouracil,
pubmed-meshheading:11759828-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:11759828-Humans,
pubmed-meshheading:11759828-Immunohistochemistry,
pubmed-meshheading:11759828-Methotrexate,
pubmed-meshheading:11759828-Middle Aged,
pubmed-meshheading:11759828-Receptor, erbB-2,
pubmed-meshheading:11759828-Up-Regulation
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| pubmed:year |
2001
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| pubmed:articleTitle |
HER-2/neu overexpression and in vitro chemosensitivity to CMF and FEC in primary breast cancer.
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| pubmed:affiliation |
Department of Medicine, UCLA School of Medicine, 90095-1678, USA. gkonecny@ucla.edu
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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