The L1 Cell Adhesion Molecule Is Induced in Renal Cancer Cells and Correlates with Metastasis in Clear Cell Carcinomas
Purpose: The L1 cell adhesion molecule is overexpressed in many human carcinomas. The objectives of the study were to provide a comprehensive description of L1 distribution in human kidney and to establish the prognostic relevance of L1 expression in renal cell carcinomas (RCC). Experimental Design:...
Gespeichert in:
| Veröffentlicht in: | Clinical cancer research 2005-02, Vol.11 (3), p.1190-1197 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1197 |
|---|---|
| container_issue | 3 |
| container_start_page | 1190 |
| container_title | Clinical cancer research |
| container_volume | 11 |
| creator | ALLORY, Yves MATSUOKA, Yasuko BAZILLE, Céline CHRISTENSEN, Erik Ilso RONCO, Pierre DEBIEC, Hanna |
| description | Purpose: The L1 cell adhesion molecule is overexpressed in many human carcinomas. The objectives of the study were to provide a comprehensive
description of L1 distribution in human kidney and to establish the prognostic relevance of L1 expression in renal cell carcinomas
(RCC).
Experimental Design: Using two antibodies to the extracellular part and the cytoplasmic domain, respectively, we first compared L1 expression
in normal kidney and renal tumors of diverse histopathologic origin, then we studied L1 expression together with tumor stage,
grade, molecular prognostic biomarkers, and metastatic behavior.
Results: In normal kidney, L1 immunoreactive with both antibodies was expressed in all epithelial cells originating from the ureteric
bud except for intercalated cells. In renal tumors, L1 was mainly detected in those originating from cells that do not express
L1 in the normal kidney [i.e., 33 of 72 clear cell RCC (ccRCC) and 25 of 88 papillary RCC (papRCC)]. Both in ccRCC and papRCC,
L1 reacted only with the antibody to the extracellular domain, suggesting that the protein was truncated. In these carcinomas,
L1 expression was strongly correlated with Ki-67 proliferation index (ccRCC, P = 0.0059; papRCC, P = 0.0039), but only in ccRCC, the presence of L1 was associated with the risk of metastasis ( P = 0.0121). This risk was higher if cyclin D1 was concurrently absent in tumor cells ( P < 0.0001). The L1 + /cyclin D1 − profile was an independent prognostic factor of metastasis occurrence in multivariate analysis ( P = 0.0023).
Conclusion: We have found a combination of markers that can serve to identify a subgroup of high-risk patients with ccRCC that may require
more aggressive therapies. |
| doi_str_mv | 10.1158/1078-0432.1190.11.3 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67424784</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>17317207</sourcerecordid><originalsourceid>FETCH-LOGICAL-c442t-84f757da34beff7edaa7e3b38b32ea0090500476af9d49d235e1d44d7cd4766d3</originalsourceid><addsrcrecordid>eNqFkU9r3DAQxUVJadK0n6AQdEnoxYlkSZZ9DKZpFzYUQnoWWmlcq2jtRGM35NtH3t2QY0Doz_B7M-I9Qr5xdsm5qq8403XBpCjzs1lql-IDOeFK6UKUlTrK91fimHxG_McYl5zJT-SYK80aXtcn5P99D3TNaQsx0mvfA4ZxoLdjBDdHoCukq8HPDjwNA72DwUba2sFB2imQ2sHTdkwJop0A6VOYenoLk8W8Ai6iNoLd01mZXBjGrcUv5GNnI8LXw3lK_tz8uG9_FevfP1ft9bpwUpZTUctOK-2tkBvoOg3eWg1iI-qNKMEy1jDFmNSV7RovG18KBdxL6bXzuVp5cUou9n0f0vg4A05mG9Dlv9gBxhlNpWUpdS3fBbkWXJdMZ1DsQZdGxASdeUhha9Oz4cwsuZjFdbO4bpZc8mZEVp0d2s-bLfg3zSGIDJwfAIvOxi5lkwO-cZWsVFM2mfu-5_rwt38KCYzbxZEAs82u343bDRYvtS2iZg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17317207</pqid></control><display><type>article</type><title>The L1 Cell Adhesion Molecule Is Induced in Renal Cancer Cells and Correlates with Metastasis in Clear Cell Carcinomas</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>ALLORY, Yves ; MATSUOKA, Yasuko ; BAZILLE, Céline ; CHRISTENSEN, Erik Ilso ; RONCO, Pierre ; DEBIEC, Hanna</creator><creatorcontrib>ALLORY, Yves ; MATSUOKA, Yasuko ; BAZILLE, Céline ; CHRISTENSEN, Erik Ilso ; RONCO, Pierre ; DEBIEC, Hanna</creatorcontrib><description>Purpose: The L1 cell adhesion molecule is overexpressed in many human carcinomas. The objectives of the study were to provide a comprehensive
description of L1 distribution in human kidney and to establish the prognostic relevance of L1 expression in renal cell carcinomas
(RCC).
Experimental Design: Using two antibodies to the extracellular part and the cytoplasmic domain, respectively, we first compared L1 expression
in normal kidney and renal tumors of diverse histopathologic origin, then we studied L1 expression together with tumor stage,
grade, molecular prognostic biomarkers, and metastatic behavior.
Results: In normal kidney, L1 immunoreactive with both antibodies was expressed in all epithelial cells originating from the ureteric
bud except for intercalated cells. In renal tumors, L1 was mainly detected in those originating from cells that do not express
L1 in the normal kidney [i.e., 33 of 72 clear cell RCC (ccRCC) and 25 of 88 papillary RCC (papRCC)]. Both in ccRCC and papRCC,
L1 reacted only with the antibody to the extracellular domain, suggesting that the protein was truncated. In these carcinomas,
L1 expression was strongly correlated with Ki-67 proliferation index (ccRCC, P = 0.0059; papRCC, P = 0.0039), but only in ccRCC, the presence of L1 was associated with the risk of metastasis ( P = 0.0121). This risk was higher if cyclin D1 was concurrently absent in tumor cells ( P < 0.0001). The L1 + /cyclin D1 − profile was an independent prognostic factor of metastasis occurrence in multivariate analysis ( P = 0.0023).
Conclusion: We have found a combination of markers that can serve to identify a subgroup of high-risk patients with ccRCC that may require
more aggressive therapies.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.1190.11.3</identifier><identifier>PMID: 15709188</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adenocarcinoma, Clear Cell - genetics ; Adenocarcinoma, Clear Cell - metabolism ; Adenocarcinoma, Clear Cell - pathology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic agents ; Biological and medical sciences ; Carcinoma, Renal Cell - genetics ; Carcinoma, Renal Cell - metabolism ; Carcinoma, Renal Cell - pathology ; Cyclin D1 - analysis ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Ki-67 Antigen - analysis ; Kidney - chemistry ; Kidney - metabolism ; Kidney Neoplasms - genetics ; Kidney Neoplasms - metabolism ; Kidney Neoplasms - pathology ; Male ; Medical sciences ; metastasis ; Middle Aged ; Neoplasm Metastasis ; Neural Cell Adhesion Molecule L1 - analysis ; Neural Cell Adhesion Molecule L1 - genetics ; Neural Cell Adhesion Molecule L1 - immunology ; Pharmacology. Drug treatments ; Prognosis ; prognostic markers ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Survival Analysis ; tissue microarray</subject><ispartof>Clinical cancer research, 2005-02, Vol.11 (3), p.1190-1197</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-84f757da34beff7edaa7e3b38b32ea0090500476af9d49d235e1d44d7cd4766d3</citedby><cites>FETCH-LOGICAL-c442t-84f757da34beff7edaa7e3b38b32ea0090500476af9d49d235e1d44d7cd4766d3</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=16465929$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15709188$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ALLORY, Yves</creatorcontrib><creatorcontrib>MATSUOKA, Yasuko</creatorcontrib><creatorcontrib>BAZILLE, Céline</creatorcontrib><creatorcontrib>CHRISTENSEN, Erik Ilso</creatorcontrib><creatorcontrib>RONCO, Pierre</creatorcontrib><creatorcontrib>DEBIEC, Hanna</creatorcontrib><title>The L1 Cell Adhesion Molecule Is Induced in Renal Cancer Cells and Correlates with Metastasis in Clear Cell Carcinomas</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: The L1 cell adhesion molecule is overexpressed in many human carcinomas. The objectives of the study were to provide a comprehensive
description of L1 distribution in human kidney and to establish the prognostic relevance of L1 expression in renal cell carcinomas
(RCC).
Experimental Design: Using two antibodies to the extracellular part and the cytoplasmic domain, respectively, we first compared L1 expression
in normal kidney and renal tumors of diverse histopathologic origin, then we studied L1 expression together with tumor stage,
grade, molecular prognostic biomarkers, and metastatic behavior.
Results: In normal kidney, L1 immunoreactive with both antibodies was expressed in all epithelial cells originating from the ureteric
bud except for intercalated cells. In renal tumors, L1 was mainly detected in those originating from cells that do not express
L1 in the normal kidney [i.e., 33 of 72 clear cell RCC (ccRCC) and 25 of 88 papillary RCC (papRCC)]. Both in ccRCC and papRCC,
L1 reacted only with the antibody to the extracellular domain, suggesting that the protein was truncated. In these carcinomas,
L1 expression was strongly correlated with Ki-67 proliferation index (ccRCC, P = 0.0059; papRCC, P = 0.0039), but only in ccRCC, the presence of L1 was associated with the risk of metastasis ( P = 0.0121). This risk was higher if cyclin D1 was concurrently absent in tumor cells ( P < 0.0001). The L1 + /cyclin D1 − profile was an independent prognostic factor of metastasis occurrence in multivariate analysis ( P = 0.0023).
Conclusion: We have found a combination of markers that can serve to identify a subgroup of high-risk patients with ccRCC that may require
more aggressive therapies.</description><subject>Adenocarcinoma, Clear Cell - genetics</subject><subject>Adenocarcinoma, Clear Cell - metabolism</subject><subject>Adenocarcinoma, Clear Cell - pathology</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Renal Cell - genetics</subject><subject>Carcinoma, Renal Cell - metabolism</subject><subject>Carcinoma, Renal Cell - pathology</subject><subject>Cyclin D1 - analysis</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization</subject><subject>Ki-67 Antigen - analysis</subject><subject>Kidney - chemistry</subject><subject>Kidney - metabolism</subject><subject>Kidney Neoplasms - genetics</subject><subject>Kidney Neoplasms - metabolism</subject><subject>Kidney Neoplasms - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>metastasis</subject><subject>Middle Aged</subject><subject>Neoplasm Metastasis</subject><subject>Neural Cell Adhesion Molecule L1 - analysis</subject><subject>Neural Cell Adhesion Molecule L1 - genetics</subject><subject>Neural Cell Adhesion Molecule L1 - immunology</subject><subject>Pharmacology. Drug treatments</subject><subject>Prognosis</subject><subject>prognostic markers</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Survival Analysis</subject><subject>tissue microarray</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9r3DAQxUVJadK0n6AQdEnoxYlkSZZ9DKZpFzYUQnoWWmlcq2jtRGM35NtH3t2QY0Doz_B7M-I9Qr5xdsm5qq8403XBpCjzs1lql-IDOeFK6UKUlTrK91fimHxG_McYl5zJT-SYK80aXtcn5P99D3TNaQsx0mvfA4ZxoLdjBDdHoCukq8HPDjwNA72DwUba2sFB2imQ2sHTdkwJop0A6VOYenoLk8W8Ai6iNoLd01mZXBjGrcUv5GNnI8LXw3lK_tz8uG9_FevfP1ft9bpwUpZTUctOK-2tkBvoOg3eWg1iI-qNKMEy1jDFmNSV7RovG18KBdxL6bXzuVp5cUou9n0f0vg4A05mG9Dlv9gBxhlNpWUpdS3fBbkWXJdMZ1DsQZdGxASdeUhha9Oz4cwsuZjFdbO4bpZc8mZEVp0d2s-bLfg3zSGIDJwfAIvOxi5lkwO-cZWsVFM2mfu-5_rwt38KCYzbxZEAs82u343bDRYvtS2iZg</recordid><startdate>20050201</startdate><enddate>20050201</enddate><creator>ALLORY, Yves</creator><creator>MATSUOKA, Yasuko</creator><creator>BAZILLE, Céline</creator><creator>CHRISTENSEN, Erik Ilso</creator><creator>RONCO, Pierre</creator><creator>DEBIEC, Hanna</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>20050201</creationdate><title>The L1 Cell Adhesion Molecule Is Induced in Renal Cancer Cells and Correlates with Metastasis in Clear Cell Carcinomas</title><author>ALLORY, Yves ; MATSUOKA, Yasuko ; BAZILLE, Céline ; CHRISTENSEN, Erik Ilso ; RONCO, Pierre ; DEBIEC, Hanna</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-84f757da34beff7edaa7e3b38b32ea0090500476af9d49d235e1d44d7cd4766d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adenocarcinoma, Clear Cell - genetics</topic><topic>Adenocarcinoma, Clear Cell - metabolism</topic><topic>Adenocarcinoma, Clear Cell - pathology</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Renal Cell - genetics</topic><topic>Carcinoma, Renal Cell - metabolism</topic><topic>Carcinoma, Renal Cell - pathology</topic><topic>Cyclin D1 - analysis</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>In Situ Hybridization</topic><topic>Ki-67 Antigen - analysis</topic><topic>Kidney - chemistry</topic><topic>Kidney - metabolism</topic><topic>Kidney Neoplasms - genetics</topic><topic>Kidney Neoplasms - metabolism</topic><topic>Kidney Neoplasms - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>metastasis</topic><topic>Middle Aged</topic><topic>Neoplasm Metastasis</topic><topic>Neural Cell Adhesion Molecule L1 - analysis</topic><topic>Neural Cell Adhesion Molecule L1 - genetics</topic><topic>Neural Cell Adhesion Molecule L1 - immunology</topic><topic>Pharmacology. Drug treatments</topic><topic>Prognosis</topic><topic>prognostic markers</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Survival Analysis</topic><topic>tissue microarray</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ALLORY, Yves</creatorcontrib><creatorcontrib>MATSUOKA, Yasuko</creatorcontrib><creatorcontrib>BAZILLE, Céline</creatorcontrib><creatorcontrib>CHRISTENSEN, Erik Ilso</creatorcontrib><creatorcontrib>RONCO, Pierre</creatorcontrib><creatorcontrib>DEBIEC, Hanna</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>ALLORY, Yves</au><au>MATSUOKA, Yasuko</au><au>BAZILLE, Céline</au><au>CHRISTENSEN, Erik Ilso</au><au>RONCO, Pierre</au><au>DEBIEC, Hanna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The L1 Cell Adhesion Molecule Is Induced in Renal Cancer Cells and Correlates with Metastasis in Clear Cell Carcinomas</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2005-02-01</date><risdate>2005</risdate><volume>11</volume><issue>3</issue><spage>1190</spage><epage>1197</epage><pages>1190-1197</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: The L1 cell adhesion molecule is overexpressed in many human carcinomas. The objectives of the study were to provide a comprehensive
description of L1 distribution in human kidney and to establish the prognostic relevance of L1 expression in renal cell carcinomas
(RCC).
Experimental Design: Using two antibodies to the extracellular part and the cytoplasmic domain, respectively, we first compared L1 expression
in normal kidney and renal tumors of diverse histopathologic origin, then we studied L1 expression together with tumor stage,
grade, molecular prognostic biomarkers, and metastatic behavior.
Results: In normal kidney, L1 immunoreactive with both antibodies was expressed in all epithelial cells originating from the ureteric
bud except for intercalated cells. In renal tumors, L1 was mainly detected in those originating from cells that do not express
L1 in the normal kidney [i.e., 33 of 72 clear cell RCC (ccRCC) and 25 of 88 papillary RCC (papRCC)]. Both in ccRCC and papRCC,
L1 reacted only with the antibody to the extracellular domain, suggesting that the protein was truncated. In these carcinomas,
L1 expression was strongly correlated with Ki-67 proliferation index (ccRCC, P = 0.0059; papRCC, P = 0.0039), but only in ccRCC, the presence of L1 was associated with the risk of metastasis ( P = 0.0121). This risk was higher if cyclin D1 was concurrently absent in tumor cells ( P < 0.0001). The L1 + /cyclin D1 − profile was an independent prognostic factor of metastasis occurrence in multivariate analysis ( P = 0.0023).
Conclusion: We have found a combination of markers that can serve to identify a subgroup of high-risk patients with ccRCC that may require
more aggressive therapies.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>15709188</pmid><doi>10.1158/1078-0432.1190.11.3</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-0432 |
| ispartof | Clinical cancer research, 2005-02, Vol.11 (3), p.1190-1197 |
| issn | 1078-0432 1557-3265 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67424784 |
| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adenocarcinoma, Clear Cell - genetics Adenocarcinoma, Clear Cell - metabolism Adenocarcinoma, Clear Cell - pathology Adolescent Adult Aged Aged, 80 and over Antineoplastic agents Biological and medical sciences Carcinoma, Renal Cell - genetics Carcinoma, Renal Cell - metabolism Carcinoma, Renal Cell - pathology Cyclin D1 - analysis Female Gene Expression Regulation, Neoplastic Humans Immunohistochemistry In Situ Hybridization Ki-67 Antigen - analysis Kidney - chemistry Kidney - metabolism Kidney Neoplasms - genetics Kidney Neoplasms - metabolism Kidney Neoplasms - pathology Male Medical sciences metastasis Middle Aged Neoplasm Metastasis Neural Cell Adhesion Molecule L1 - analysis Neural Cell Adhesion Molecule L1 - genetics Neural Cell Adhesion Molecule L1 - immunology Pharmacology. Drug treatments Prognosis prognostic markers RNA, Messenger - genetics RNA, Messenger - metabolism Survival Analysis tissue microarray |
| title | The L1 Cell Adhesion Molecule Is Induced in Renal Cancer Cells and Correlates with Metastasis in Clear Cell Carcinomas |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T20%3A25%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20L1%20Cell%20Adhesion%20Molecule%20Is%20Induced%20in%20Renal%20Cancer%20Cells%20and%20Correlates%20with%20Metastasis%20in%20Clear%20Cell%20Carcinomas&rft.jtitle=Clinical%20cancer%20research&rft.au=ALLORY,%20Yves&rft.date=2005-02-01&rft.volume=11&rft.issue=3&rft.spage=1190&rft.epage=1197&rft.pages=1190-1197&rft.issn=1078-0432&rft.eissn=1557-3265&rft_id=info:doi/10.1158/1078-0432.1190.11.3&rft_dat=%3Cproquest_cross%3E17317207%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=17317207&rft_id=info:pmid/15709188&rfr_iscdi=true |