The Prognostic Value of BCAR1 in Patients with Primary Breast Cancer
Purpose: BCAR1, the human homologue of the rat p130Cas protein, was identified in a functional screen for human breast cancer cell proliferation resistant to antiestrogen drugs. Here, we study the prognostic value of quantitative BCAR1 levels in a large series of breast cancer specimens. Experimenta...
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| Veröffentlicht in: | Clinical cancer research 2004-09, Vol.10 (18), p.6194-6202 |
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| creator | Dorssers, Lambert C J Grebenchtchikov, Nicolai Brinkman, Arend Look, Maxime P van Broekhoven, Simone P J de Jong, Danielle Peters, Harry A Portengen, Henk Meijer-van Gelder, Marion E Klijn, Jan G M van Tienoven, Doorlene T H Geurts-Moespot, Anneke Span, Paul N Foekens, John A Sweep, Fred C G J |
| description | Purpose: BCAR1, the human homologue of the rat p130Cas protein, was identified in a functional screen for human breast cancer cell
proliferation resistant to antiestrogen drugs. Here, we study the prognostic value of quantitative BCAR1 levels in a large
series of breast cancer specimens.
Experimental Design: A specific ELISA was developed to measure BCAR1 protein levels in 2593 primary breast tumor cytosols. Tumor levels of BCAR1
were correlated with relapse-free survival (RFS) and overall survival (OS) and compared with collected data on urokinase-type
plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1).
Results: In tumor cytosols, BCAR1 protein levels varied between 0.02 and 23 ng/mg protein. BCAR1 levels exhibited a positive correlation
with steroid hormone receptor levels, age and menopausal status, and uPA and PAI-1 levels. The level of BCAR1 (continuous
or categorized as low, intermediate, or high) was inversely related with RFS and OS time. Multivariate analysis showed that
BCAR1 levels contributed independently to a base model containing the traditional prognostic factors for both RFS and OS (both
P < 0.0001). When added together with uPA and PAI-1 in the multivariate model, BCAR1 contributed independently of PAI-1 and
was favored over uPA. Interaction tests allowed for additional analyses of BCAR1 protein levels in clinically relevant subgroups
stratified by nodal and menopausal status.
Conclusions: The quantitative BCAR1 protein level represents a prognostic factor for RFS and OS in primary breast cancer, independent
of the traditional prognostic factors and the other novel marker PAI-1. |
| doi_str_mv | 10.1158/1078-0432.CCR-04-0444 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_66911751</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>17694075</sourcerecordid><originalsourceid>FETCH-LOGICAL-c433t-7520f5761cb65bd57dc3b943526c38057869858caf64fa8b7aaae5cbcfd838453</originalsourceid><addsrcrecordid>eNqFkUtr3DAURkVpaB7tT2jRpqFZONW1dCV5OXHzgkBDSLsVskaOVTx2InkI-feRM1OyS0Cguzj3wfkI-QrsGAD1T2BKF0zw8riub3KRnxAfyB4gqoKXEj_m-j-zS_ZT-scYCGDiE9kFFEIzpvbIr9vO0-s43g1jmoKjf22_9nRs6Um9uAEaBnptp-CHKdHHMHUZDSsbn-hJ9DZNtLaD8_Ez2Wltn_yX7X9A_pyd3tYXxdXv88t6cVU4wflUKCxZi0qCayQ2S1RLx5tKcCyl45qh0rLSqJ1tpWitbpS11qNrXLvUXAvkB-RwM_c-jg9rnyazCsn5vreDH9fJSFkBKIQM_ngTBK1QCwmCvTsTlKwEU_Ny3IAujilF35r7jQsDzMyRmFm3mXWbHEkuzBxJ7vu2XbBuVn752rXNIAPft4BNzvZtzE5DeuXymaDLKnNHG64Ld91jiN64F_vRJ2-j617u0EZCVvoMhFSfjw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17694075</pqid></control><display><type>article</type><title>The Prognostic Value of BCAR1 in Patients with Primary Breast Cancer</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Dorssers, Lambert C J ; Grebenchtchikov, Nicolai ; Brinkman, Arend ; Look, Maxime P ; van Broekhoven, Simone P J ; de Jong, Danielle ; Peters, Harry A ; Portengen, Henk ; Meijer-van Gelder, Marion E ; Klijn, Jan G M ; van Tienoven, Doorlene T H ; Geurts-Moespot, Anneke ; Span, Paul N ; Foekens, John A ; Sweep, Fred C G J</creator><creatorcontrib>Dorssers, Lambert C J ; Grebenchtchikov, Nicolai ; Brinkman, Arend ; Look, Maxime P ; van Broekhoven, Simone P J ; de Jong, Danielle ; Peters, Harry A ; Portengen, Henk ; Meijer-van Gelder, Marion E ; Klijn, Jan G M ; van Tienoven, Doorlene T H ; Geurts-Moespot, Anneke ; Span, Paul N ; Foekens, John A ; Sweep, Fred C G J</creatorcontrib><description>Purpose: BCAR1, the human homologue of the rat p130Cas protein, was identified in a functional screen for human breast cancer cell
proliferation resistant to antiestrogen drugs. Here, we study the prognostic value of quantitative BCAR1 levels in a large
series of breast cancer specimens.
Experimental Design: A specific ELISA was developed to measure BCAR1 protein levels in 2593 primary breast tumor cytosols. Tumor levels of BCAR1
were correlated with relapse-free survival (RFS) and overall survival (OS) and compared with collected data on urokinase-type
plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1).
Results: In tumor cytosols, BCAR1 protein levels varied between 0.02 and 23 ng/mg protein. BCAR1 levels exhibited a positive correlation
with steroid hormone receptor levels, age and menopausal status, and uPA and PAI-1 levels. The level of BCAR1 (continuous
or categorized as low, intermediate, or high) was inversely related with RFS and OS time. Multivariate analysis showed that
BCAR1 levels contributed independently to a base model containing the traditional prognostic factors for both RFS and OS (both
P < 0.0001). When added together with uPA and PAI-1 in the multivariate model, BCAR1 contributed independently of PAI-1 and
was favored over uPA. Interaction tests allowed for additional analyses of BCAR1 protein levels in clinically relevant subgroups
stratified by nodal and menopausal status.
Conclusions: The quantitative BCAR1 protein level represents a prognostic factor for RFS and OS in primary breast cancer, independent
of the traditional prognostic factors and the other novel marker PAI-1.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-04-0444</identifier><identifier>PMID: 15448007</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adult ; Aged ; Antineoplastic agents ; Biological and medical sciences ; Breast Neoplasms - diagnosis ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Cell Line, Tumor ; Cell Proliferation ; Chemotherapy, Adjuvant ; Crk-Associated Substrate Protein ; Cytosol - metabolism ; Disease-Free Survival ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Likelihood Functions ; Medical sciences ; Middle Aged ; Multivariate Analysis ; Pharmacology. Drug treatments ; Plasminogen Activator Inhibitor 1 - metabolism ; Prognosis ; Proportional Hazards Models ; Proteins - genetics ; Recurrence ; Retinoblastoma-Like Protein p130 ; Tumors ; Urokinase-Type Plasminogen Activator - metabolism</subject><ispartof>Clinical cancer research, 2004-09, Vol.10 (18), p.6194-6202</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c433t-7520f5761cb65bd57dc3b943526c38057869858caf64fa8b7aaae5cbcfd838453</citedby><cites>FETCH-LOGICAL-c433t-7520f5761cb65bd57dc3b943526c38057869858caf64fa8b7aaae5cbcfd838453</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3343,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16141829$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15448007$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dorssers, Lambert C J</creatorcontrib><creatorcontrib>Grebenchtchikov, Nicolai</creatorcontrib><creatorcontrib>Brinkman, Arend</creatorcontrib><creatorcontrib>Look, Maxime P</creatorcontrib><creatorcontrib>van Broekhoven, Simone P J</creatorcontrib><creatorcontrib>de Jong, Danielle</creatorcontrib><creatorcontrib>Peters, Harry A</creatorcontrib><creatorcontrib>Portengen, Henk</creatorcontrib><creatorcontrib>Meijer-van Gelder, Marion E</creatorcontrib><creatorcontrib>Klijn, Jan G M</creatorcontrib><creatorcontrib>van Tienoven, Doorlene T H</creatorcontrib><creatorcontrib>Geurts-Moespot, Anneke</creatorcontrib><creatorcontrib>Span, Paul N</creatorcontrib><creatorcontrib>Foekens, John A</creatorcontrib><creatorcontrib>Sweep, Fred C G J</creatorcontrib><title>The Prognostic Value of BCAR1 in Patients with Primary Breast Cancer</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: BCAR1, the human homologue of the rat p130Cas protein, was identified in a functional screen for human breast cancer cell
proliferation resistant to antiestrogen drugs. Here, we study the prognostic value of quantitative BCAR1 levels in a large
series of breast cancer specimens.
Experimental Design: A specific ELISA was developed to measure BCAR1 protein levels in 2593 primary breast tumor cytosols. Tumor levels of BCAR1
were correlated with relapse-free survival (RFS) and overall survival (OS) and compared with collected data on urokinase-type
plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1).
Results: In tumor cytosols, BCAR1 protein levels varied between 0.02 and 23 ng/mg protein. BCAR1 levels exhibited a positive correlation
with steroid hormone receptor levels, age and menopausal status, and uPA and PAI-1 levels. The level of BCAR1 (continuous
or categorized as low, intermediate, or high) was inversely related with RFS and OS time. Multivariate analysis showed that
BCAR1 levels contributed independently to a base model containing the traditional prognostic factors for both RFS and OS (both
P < 0.0001). When added together with uPA and PAI-1 in the multivariate model, BCAR1 contributed independently of PAI-1 and
was favored over uPA. Interaction tests allowed for additional analyses of BCAR1 protein levels in clinically relevant subgroups
stratified by nodal and menopausal status.
Conclusions: The quantitative BCAR1 protein level represents a prognostic factor for RFS and OS in primary breast cancer, independent
of the traditional prognostic factors and the other novel marker PAI-1.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Breast Neoplasms - diagnosis</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Chemotherapy, Adjuvant</subject><subject>Crk-Associated Substrate Protein</subject><subject>Cytosol - metabolism</subject><subject>Disease-Free Survival</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Humans</subject><subject>Likelihood Functions</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Pharmacology. Drug treatments</subject><subject>Plasminogen Activator Inhibitor 1 - metabolism</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Proteins - genetics</subject><subject>Recurrence</subject><subject>Retinoblastoma-Like Protein p130</subject><subject>Tumors</subject><subject>Urokinase-Type Plasminogen Activator - metabolism</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtr3DAURkVpaB7tT2jRpqFZONW1dCV5OXHzgkBDSLsVskaOVTx2InkI-feRM1OyS0Cguzj3wfkI-QrsGAD1T2BKF0zw8riub3KRnxAfyB4gqoKXEj_m-j-zS_ZT-scYCGDiE9kFFEIzpvbIr9vO0-s43g1jmoKjf22_9nRs6Um9uAEaBnptp-CHKdHHMHUZDSsbn-hJ9DZNtLaD8_Ez2Wltn_yX7X9A_pyd3tYXxdXv88t6cVU4wflUKCxZi0qCayQ2S1RLx5tKcCyl45qh0rLSqJ1tpWitbpS11qNrXLvUXAvkB-RwM_c-jg9rnyazCsn5vreDH9fJSFkBKIQM_ngTBK1QCwmCvTsTlKwEU_Ny3IAujilF35r7jQsDzMyRmFm3mXWbHEkuzBxJ7vu2XbBuVn752rXNIAPft4BNzvZtzE5DeuXymaDLKnNHG64Ld91jiN64F_vRJ2-j617u0EZCVvoMhFSfjw</recordid><startdate>20040915</startdate><enddate>20040915</enddate><creator>Dorssers, Lambert C J</creator><creator>Grebenchtchikov, Nicolai</creator><creator>Brinkman, Arend</creator><creator>Look, Maxime P</creator><creator>van Broekhoven, Simone P J</creator><creator>de Jong, Danielle</creator><creator>Peters, Harry A</creator><creator>Portengen, Henk</creator><creator>Meijer-van Gelder, Marion E</creator><creator>Klijn, Jan G M</creator><creator>van Tienoven, Doorlene T H</creator><creator>Geurts-Moespot, Anneke</creator><creator>Span, Paul N</creator><creator>Foekens, John A</creator><creator>Sweep, Fred C G J</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20040915</creationdate><title>The Prognostic Value of BCAR1 in Patients with Primary Breast Cancer</title><author>Dorssers, Lambert C J ; Grebenchtchikov, Nicolai ; Brinkman, Arend ; Look, Maxime P ; van Broekhoven, Simone P J ; de Jong, Danielle ; Peters, Harry A ; Portengen, Henk ; Meijer-van Gelder, Marion E ; Klijn, Jan G M ; van Tienoven, Doorlene T H ; Geurts-Moespot, Anneke ; Span, Paul N ; Foekens, John A ; Sweep, Fred C G J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c433t-7520f5761cb65bd57dc3b943526c38057869858caf64fa8b7aaae5cbcfd838453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Breast Neoplasms - diagnosis</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Chemotherapy, Adjuvant</topic><topic>Crk-Associated Substrate Protein</topic><topic>Cytosol - metabolism</topic><topic>Disease-Free Survival</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Humans</topic><topic>Likelihood Functions</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>Pharmacology. Drug treatments</topic><topic>Plasminogen Activator Inhibitor 1 - metabolism</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Proteins - genetics</topic><topic>Recurrence</topic><topic>Retinoblastoma-Like Protein p130</topic><topic>Tumors</topic><topic>Urokinase-Type Plasminogen Activator - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dorssers, Lambert C J</creatorcontrib><creatorcontrib>Grebenchtchikov, Nicolai</creatorcontrib><creatorcontrib>Brinkman, Arend</creatorcontrib><creatorcontrib>Look, Maxime P</creatorcontrib><creatorcontrib>van Broekhoven, Simone P J</creatorcontrib><creatorcontrib>de Jong, Danielle</creatorcontrib><creatorcontrib>Peters, Harry A</creatorcontrib><creatorcontrib>Portengen, Henk</creatorcontrib><creatorcontrib>Meijer-van Gelder, Marion E</creatorcontrib><creatorcontrib>Klijn, Jan G M</creatorcontrib><creatorcontrib>van Tienoven, Doorlene T H</creatorcontrib><creatorcontrib>Geurts-Moespot, Anneke</creatorcontrib><creatorcontrib>Span, Paul N</creatorcontrib><creatorcontrib>Foekens, John A</creatorcontrib><creatorcontrib>Sweep, Fred C G J</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dorssers, Lambert C J</au><au>Grebenchtchikov, Nicolai</au><au>Brinkman, Arend</au><au>Look, Maxime P</au><au>van Broekhoven, Simone P J</au><au>de Jong, Danielle</au><au>Peters, Harry A</au><au>Portengen, Henk</au><au>Meijer-van Gelder, Marion E</au><au>Klijn, Jan G M</au><au>van Tienoven, Doorlene T H</au><au>Geurts-Moespot, Anneke</au><au>Span, Paul N</au><au>Foekens, John A</au><au>Sweep, Fred C G J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Prognostic Value of BCAR1 in Patients with Primary Breast Cancer</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2004-09-15</date><risdate>2004</risdate><volume>10</volume><issue>18</issue><spage>6194</spage><epage>6202</epage><pages>6194-6202</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: BCAR1, the human homologue of the rat p130Cas protein, was identified in a functional screen for human breast cancer cell
proliferation resistant to antiestrogen drugs. Here, we study the prognostic value of quantitative BCAR1 levels in a large
series of breast cancer specimens.
Experimental Design: A specific ELISA was developed to measure BCAR1 protein levels in 2593 primary breast tumor cytosols. Tumor levels of BCAR1
were correlated with relapse-free survival (RFS) and overall survival (OS) and compared with collected data on urokinase-type
plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1).
Results: In tumor cytosols, BCAR1 protein levels varied between 0.02 and 23 ng/mg protein. BCAR1 levels exhibited a positive correlation
with steroid hormone receptor levels, age and menopausal status, and uPA and PAI-1 levels. The level of BCAR1 (continuous
or categorized as low, intermediate, or high) was inversely related with RFS and OS time. Multivariate analysis showed that
BCAR1 levels contributed independently to a base model containing the traditional prognostic factors for both RFS and OS (both
P < 0.0001). When added together with uPA and PAI-1 in the multivariate model, BCAR1 contributed independently of PAI-1 and
was favored over uPA. Interaction tests allowed for additional analyses of BCAR1 protein levels in clinically relevant subgroups
stratified by nodal and menopausal status.
Conclusions: The quantitative BCAR1 protein level represents a prognostic factor for RFS and OS in primary breast cancer, independent
of the traditional prognostic factors and the other novel marker PAI-1.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>15448007</pmid><doi>10.1158/1078-0432.CCR-04-0444</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Aged Antineoplastic agents Biological and medical sciences Breast Neoplasms - diagnosis Breast Neoplasms - genetics Breast Neoplasms - metabolism Cell Line, Tumor Cell Proliferation Chemotherapy, Adjuvant Crk-Associated Substrate Protein Cytosol - metabolism Disease-Free Survival Enzyme-Linked Immunosorbent Assay Female Humans Likelihood Functions Medical sciences Middle Aged Multivariate Analysis Pharmacology. Drug treatments Plasminogen Activator Inhibitor 1 - metabolism Prognosis Proportional Hazards Models Proteins - genetics Recurrence Retinoblastoma-Like Protein p130 Tumors Urokinase-Type Plasminogen Activator - metabolism |
| title | The Prognostic Value of BCAR1 in Patients with Primary Breast Cancer |
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