Source:http://linkedlifedata.com/resource/pubmed/id/11595720
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions |
umls-concept:C0007600,
umls-concept:C0017262,
umls-concept:C0021044,
umls-concept:C0086418,
umls-concept:C0162789,
umls-concept:C0185117,
umls-concept:C0242957,
umls-concept:C0334227,
umls-concept:C0439849,
umls-concept:C0596402,
umls-concept:C0684249,
umls-concept:C0728747,
umls-concept:C0729502,
umls-concept:C1533691,
umls-concept:C2911684
|
pubmed:issue |
10
|
pubmed:dateCreated |
2001-10-11
|
pubmed:abstractText |
Overexpression of the Her-2/neu oncogene and receptor protein was reported in approximately 20% of breast cancers and was associated with a poor prognosis. Her-2/neu expression was a predictor for response to trastuzumab, a monoclonal antibody that recognizes the Her-2/neu cell surface receptor. Data regarding the expression of Her-2/neu in lung cancer are far more limited, and there is little information regarding the influence of Her-2/neu expression and response to trastuzumab alone or in combination with chemotherapeutic agents. In this report we evaluated Her-2/neu gene expression by fluorescence in situ hybridization (FISH) and the cell surface expression of the Her-2/neu receptor by immunohistochemistry using the HercepTest and by FACS analysis in 31 lung cancer cell lines with 5 breast cancer cell lines as controls. By FACS, we found Her-2/neu overexpression (mean fluorescence intensity >8) in 2 of the 22 non-small cell lung cancer (NSCLC) cell lines (9%), none of 11 small cell lung cancer (SCLC) cell lines, and 4 of 5 breast cancer cell lines. A positive HercepTest (2+ or 3+) was found in 6 of 19 NSCLC cell lines (26%, 2+; 5%, 3+), 1 of 3 SCLC cell lines (33%), and 4 of 5 breast cancer cell lines (80%). One of 6 NSCLC cell lines examined (17%) had gene amplification with >32 copies of Her-2/neu/cell and had homogeneous staining regions. One NSCLC cell line had a maximum of 14 copies of Her-2/neu/cell, and 3 had modest increases in Her-2/neu gene copy number without gene amplification (maximum 5-8 copies/cell). None of the SCLC cell lines had more than a maximum of 4 copies/cell, whereas the 2 breast cancer cell lines had maximum Her-2/neu copy numbers of 80 and 5, respectively. Aneusomy rather than true amplification was the major cause of increased Her-2/neu expression in most of the NSCLC cell lines. There was a strong correlation when the results of fluorescence-activated cell sorter, HercepTest results, and FISH were compared in pairs. Furthermore, Trastuzumab produced a G(1) cell cycle arrest and growth inhibition only in cell lines expressing Her-2/neu. The IC(50) for growth inhibition was correlated with cell surface Her-2/neu expression. The combination of trastuzumab and chemotherapeutic agents produced more than additive growth inhibition in cell lines expressing Her-2/neu, but the level of additivity was not related to the amount of Her-2/neu expression. These data indicate that trastuzumab alone and in combination with chemotherapeutic agents should be tested in NSCLC patients and that Her-2/neu should be assessed by both immunohistochemistry and FISH methods in these studies to determine which test is the best predictor of outcome.
|
pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal, Humanized,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cisplatin,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxycytidine,
http://linkedlifedata.com/resource/pubmed/chemical/Paclitaxel,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2,
http://linkedlifedata.com/resource/pubmed/chemical/Vinblastine,
http://linkedlifedata.com/resource/pubmed/chemical/gemcitabine,
http://linkedlifedata.com/resource/pubmed/chemical/trastuzumab,
http://linkedlifedata.com/resource/pubmed/chemical/vinorelbine
|
pubmed:status |
MEDLINE
|
pubmed:month |
Oct
|
pubmed:issn |
1078-0432
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
7
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
3239-50
|
pubmed:dateRevised |
2011-11-17
|
pubmed:meshHeading |
pubmed-meshheading:11595720-Antibodies, Monoclonal,
pubmed-meshheading:11595720-Antibodies, Monoclonal, Humanized,
pubmed-meshheading:11595720-Antineoplastic Agents,
pubmed-meshheading:11595720-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:11595720-Cell Cycle,
pubmed-meshheading:11595720-Cell Division,
pubmed-meshheading:11595720-Cisplatin,
pubmed-meshheading:11595720-Deoxycytidine,
pubmed-meshheading:11595720-Dose-Response Relationship, Drug,
pubmed-meshheading:11595720-Drug Synergism,
pubmed-meshheading:11595720-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:11595720-Humans,
pubmed-meshheading:11595720-Immunohistochemistry,
pubmed-meshheading:11595720-In Situ Hybridization, Fluorescence,
pubmed-meshheading:11595720-Lung Neoplasms,
pubmed-meshheading:11595720-Paclitaxel,
pubmed-meshheading:11595720-Receptor, erbB-2,
pubmed-meshheading:11595720-Tumor Cells, Cultured,
pubmed-meshheading:11595720-Vinblastine
|
pubmed:year |
2001
|
pubmed:articleTitle |
Expression of Her-2/neu in human lung cancer cell lines by immunohistochemistry and fluorescence in situ hybridization and its relationship to in vitro cytotoxicity by trastuzumab and chemotherapeutic agents.
|
pubmed:affiliation |
Lung Cancer Program, Department of Medicine, University of Colorado Cancer Center, 4200 East Ninth Avenue, Denver CO 80262, USA.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|