Silencing of GLUT-1 inhibits sensitization of oral cancer cells to cisplatin during hypoxia
Background During tumor development, cells are exposed to a hypoxic microenvironment. Tumor hypoxia also has a profound influence on the sensitivity of cancer chemotherapy. The objective of this study was to investigate the mechanism of cisplatin (CDDP) resistance of oral squamous cell carcinoma (OS...
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| Veröffentlicht in: | Journal of oral pathology & medicine 2013-05, Vol.42 (5), p.382-388 |
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| container_title | Journal of oral pathology & medicine |
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| creator | Shimanishi, Makoto Ogi, Kazuhiro Sogabe, Yohei Kaneko, Takeshi Dehari, Hironari Miyazaki, Akihiro Hiratsuka, Hiroyoshi |
| description | Background
During tumor development, cells are exposed to a hypoxic microenvironment. Tumor hypoxia also has a profound influence on the sensitivity of cancer chemotherapy.
The objective of this study was to investigate the mechanism of cisplatin (CDDP) resistance of oral squamous cell carcinoma (OSCC) cells under hypoxia by analyzing gene expression profiles to identify key genes and factors involved.
Methods
Cell viability was measured following culture of the cells in the presence or absence of CDDP, under normoxic or hypoxic conditions, using a CCK‐8 assay. Analysis of the expression of HIF target genes in hypoxia‐treated cells was performed using an HIF‐regulated cDNA plate array. Changes in the mRNA expression of selected HIF target genes were analyzed using RT‐PCR, and changes in the protein levels of these genes were analyzed by Western blotting. Tumor cell apoptosis was assessed by flow cytometry.
Results
The OSCC cell lines responded differently to CDDP under normoxic and hypoxic conditions. The expression of glucose transporter protein‐1 (GLUT‐1) was up‐regulated in human squamous cell carcinoma of mouth (HSC‐2) cells under hypoxia. Furthermore, there was little correlation between the cisplatin sensitivity of human squamous cell carcinoma of tongue (SAS) in normoxia and hypoxia. After GLUT‐1 knockdown, CDDP treatment resulted in increased rates of apoptosis under hypoxia as compared with normoxia in cell lines HSC‐2, Ca9‐22, and SAS (P = 0.025).
Conclusion
The results of this study suggest that knockdown of GLUT‐1 inhibits sensitization of oral squamous cells to CDDP during hypoxia in HSC‐2, Ca9‐22, and SAS cells. |
| doi_str_mv | 10.1111/jop.12028 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1338395628</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1338395628</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4298-27969ddf3e7f4e61845bb4940edc858da05a9e774560fa780372cfcfa9faa1563</originalsourceid><addsrcrecordid>eNp1kLtOwzAUQC0EgvIY-AHkEYaAX4ntESooj_ISRQwMluvYYEjjYKeC8vWkFNi4y13OPbo6AGxjtI-7OXgJzT4miIgl0MMFQhnimC2DHpKIZSTHZA2sp_SCEOaU4VWwRighXEjSA493vrK18fUTDA4OhvejDENfP_uxbxNMtk6-9Z-69aGeAyHqChpdGxuhsVWVYBug8ampOqSG5TTOTc-zJnx4vQlWnK6S3frZG-D-5HjUP82G14Oz_uEwM4xIkREuC1mWjlrumC2wYPl4zCRDtjQiF6VGuZaWc5YXyGkuEOXEOOO0dFrjvKAbYHfhbWJ4m9rUqolP8-90bcM0KUypoDIviOjQvQVqYkgpWqea6Cc6zhRGat5SdS3Vd8uO3fnRTscTW_6Rv_E64GABvHcNZ_-b1Pn1za8yW1z41NqPvwsdX1XBKc_Vw9VAkYujkxG-FOqWfgFUSoz3</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1338395628</pqid></control><display><type>article</type><title>Silencing of GLUT-1 inhibits sensitization of oral cancer cells to cisplatin during hypoxia</title><source>Wiley-Blackwell Journals</source><source>MEDLINE</source><creator>Shimanishi, Makoto ; Ogi, Kazuhiro ; Sogabe, Yohei ; Kaneko, Takeshi ; Dehari, Hironari ; Miyazaki, Akihiro ; Hiratsuka, Hiroyoshi</creator><creatorcontrib>Shimanishi, Makoto ; Ogi, Kazuhiro ; Sogabe, Yohei ; Kaneko, Takeshi ; Dehari, Hironari ; Miyazaki, Akihiro ; Hiratsuka, Hiroyoshi</creatorcontrib><description>Background
During tumor development, cells are exposed to a hypoxic microenvironment. Tumor hypoxia also has a profound influence on the sensitivity of cancer chemotherapy.
The objective of this study was to investigate the mechanism of cisplatin (CDDP) resistance of oral squamous cell carcinoma (OSCC) cells under hypoxia by analyzing gene expression profiles to identify key genes and factors involved.
Methods
Cell viability was measured following culture of the cells in the presence or absence of CDDP, under normoxic or hypoxic conditions, using a CCK‐8 assay. Analysis of the expression of HIF target genes in hypoxia‐treated cells was performed using an HIF‐regulated cDNA plate array. Changes in the mRNA expression of selected HIF target genes were analyzed using RT‐PCR, and changes in the protein levels of these genes were analyzed by Western blotting. Tumor cell apoptosis was assessed by flow cytometry.
Results
The OSCC cell lines responded differently to CDDP under normoxic and hypoxic conditions. The expression of glucose transporter protein‐1 (GLUT‐1) was up‐regulated in human squamous cell carcinoma of mouth (HSC‐2) cells under hypoxia. Furthermore, there was little correlation between the cisplatin sensitivity of human squamous cell carcinoma of tongue (SAS) in normoxia and hypoxia. After GLUT‐1 knockdown, CDDP treatment resulted in increased rates of apoptosis under hypoxia as compared with normoxia in cell lines HSC‐2, Ca9‐22, and SAS (P = 0.025).
Conclusion
The results of this study suggest that knockdown of GLUT‐1 inhibits sensitization of oral squamous cells to CDDP during hypoxia in HSC‐2, Ca9‐22, and SAS cells.</description><identifier>ISSN: 0904-2512</identifier><identifier>EISSN: 1600-0714</identifier><identifier>DOI: 10.1111/jop.12028</identifier><identifier>PMID: 23227892</identifier><language>eng</language><publisher>Denmark: Blackwell Publishing Ltd</publisher><subject>Antineoplastic Agents - therapeutic use ; Apoptosis - drug effects ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Carcinoma, Squamous Cell - drug therapy ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - pathology ; Cell Culture Techniques ; Cell Death - drug effects ; Cell Death - genetics ; Cell Hypoxia - physiology ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival - drug effects ; cisplatin (CDDP) ; Cisplatin - therapeutic use ; Dentistry ; Drug Resistance, Neoplasm - drug effects ; Drug Resistance, Neoplasm - genetics ; Gene Expression Profiling ; Gene Knockdown Techniques ; Gene Silencing ; Glucose Transporter Type 1 - genetics ; glucose transporter-1(GLUT-1) ; Humans ; hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit - genetics ; Mouth Neoplasms - drug therapy ; Mouth Neoplasms - genetics ; Mouth Neoplasms - pathology ; oral squamous cell carcinoma ; RNA, Small Interfering - genetics ; Tongue Neoplasms - drug therapy ; Tongue Neoplasms - pathology ; Tumor Microenvironment - drug effects ; Tumor Microenvironment - genetics</subject><ispartof>Journal of oral pathology & medicine, 2013-05, Vol.42 (5), p.382-388</ispartof><rights>2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd</rights><rights>2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4298-27969ddf3e7f4e61845bb4940edc858da05a9e774560fa780372cfcfa9faa1563</citedby><cites>FETCH-LOGICAL-c4298-27969ddf3e7f4e61845bb4940edc858da05a9e774560fa780372cfcfa9faa1563</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjop.12028$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjop.12028$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23227892$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shimanishi, Makoto</creatorcontrib><creatorcontrib>Ogi, Kazuhiro</creatorcontrib><creatorcontrib>Sogabe, Yohei</creatorcontrib><creatorcontrib>Kaneko, Takeshi</creatorcontrib><creatorcontrib>Dehari, Hironari</creatorcontrib><creatorcontrib>Miyazaki, Akihiro</creatorcontrib><creatorcontrib>Hiratsuka, Hiroyoshi</creatorcontrib><title>Silencing of GLUT-1 inhibits sensitization of oral cancer cells to cisplatin during hypoxia</title><title>Journal of oral pathology & medicine</title><addtitle>J Oral Pathol Med</addtitle><description>Background
During tumor development, cells are exposed to a hypoxic microenvironment. Tumor hypoxia also has a profound influence on the sensitivity of cancer chemotherapy.
The objective of this study was to investigate the mechanism of cisplatin (CDDP) resistance of oral squamous cell carcinoma (OSCC) cells under hypoxia by analyzing gene expression profiles to identify key genes and factors involved.
Methods
Cell viability was measured following culture of the cells in the presence or absence of CDDP, under normoxic or hypoxic conditions, using a CCK‐8 assay. Analysis of the expression of HIF target genes in hypoxia‐treated cells was performed using an HIF‐regulated cDNA plate array. Changes in the mRNA expression of selected HIF target genes were analyzed using RT‐PCR, and changes in the protein levels of these genes were analyzed by Western blotting. Tumor cell apoptosis was assessed by flow cytometry.
Results
The OSCC cell lines responded differently to CDDP under normoxic and hypoxic conditions. The expression of glucose transporter protein‐1 (GLUT‐1) was up‐regulated in human squamous cell carcinoma of mouth (HSC‐2) cells under hypoxia. Furthermore, there was little correlation between the cisplatin sensitivity of human squamous cell carcinoma of tongue (SAS) in normoxia and hypoxia. After GLUT‐1 knockdown, CDDP treatment resulted in increased rates of apoptosis under hypoxia as compared with normoxia in cell lines HSC‐2, Ca9‐22, and SAS (P = 0.025).
Conclusion
The results of this study suggest that knockdown of GLUT‐1 inhibits sensitization of oral squamous cells to CDDP during hypoxia in HSC‐2, Ca9‐22, and SAS cells.</description><subject>Antineoplastic Agents - therapeutic use</subject><subject>Apoptosis - drug effects</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Carcinoma, Squamous Cell - drug therapy</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cell Culture Techniques</subject><subject>Cell Death - drug effects</subject><subject>Cell Death - genetics</subject><subject>Cell Hypoxia - physiology</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cell Survival - drug effects</subject><subject>cisplatin (CDDP)</subject><subject>Cisplatin - therapeutic use</subject><subject>Dentistry</subject><subject>Drug Resistance, Neoplasm - drug effects</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Gene Expression Profiling</subject><subject>Gene Knockdown Techniques</subject><subject>Gene Silencing</subject><subject>Glucose Transporter Type 1 - genetics</subject><subject>glucose transporter-1(GLUT-1)</subject><subject>Humans</subject><subject>hypoxia</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - genetics</subject><subject>Mouth Neoplasms - drug therapy</subject><subject>Mouth Neoplasms - genetics</subject><subject>Mouth Neoplasms - pathology</subject><subject>oral squamous cell carcinoma</subject><subject>RNA, Small Interfering - genetics</subject><subject>Tongue Neoplasms - drug therapy</subject><subject>Tongue Neoplasms - pathology</subject><subject>Tumor Microenvironment - drug effects</subject><subject>Tumor Microenvironment - genetics</subject><issn>0904-2512</issn><issn>1600-0714</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kLtOwzAUQC0EgvIY-AHkEYaAX4ntESooj_ISRQwMluvYYEjjYKeC8vWkFNi4y13OPbo6AGxjtI-7OXgJzT4miIgl0MMFQhnimC2DHpKIZSTHZA2sp_SCEOaU4VWwRighXEjSA493vrK18fUTDA4OhvejDENfP_uxbxNMtk6-9Z-69aGeAyHqChpdGxuhsVWVYBug8ampOqSG5TTOTc-zJnx4vQlWnK6S3frZG-D-5HjUP82G14Oz_uEwM4xIkREuC1mWjlrumC2wYPl4zCRDtjQiF6VGuZaWc5YXyGkuEOXEOOO0dFrjvKAbYHfhbWJ4m9rUqolP8-90bcM0KUypoDIviOjQvQVqYkgpWqea6Cc6zhRGat5SdS3Vd8uO3fnRTscTW_6Rv_E64GABvHcNZ_-b1Pn1za8yW1z41NqPvwsdX1XBKc_Vw9VAkYujkxG-FOqWfgFUSoz3</recordid><startdate>201305</startdate><enddate>201305</enddate><creator>Shimanishi, Makoto</creator><creator>Ogi, Kazuhiro</creator><creator>Sogabe, Yohei</creator><creator>Kaneko, Takeshi</creator><creator>Dehari, Hironari</creator><creator>Miyazaki, Akihiro</creator><creator>Hiratsuka, Hiroyoshi</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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>7X8</scope></search><sort><creationdate>201305</creationdate><title>Silencing of GLUT-1 inhibits sensitization of oral cancer cells to cisplatin during hypoxia</title><author>Shimanishi, Makoto ; Ogi, Kazuhiro ; Sogabe, Yohei ; Kaneko, Takeshi ; Dehari, Hironari ; Miyazaki, Akihiro ; Hiratsuka, Hiroyoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4298-27969ddf3e7f4e61845bb4940edc858da05a9e774560fa780372cfcfa9faa1563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Antineoplastic Agents - therapeutic use</topic><topic>Apoptosis - drug effects</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Carcinoma, Squamous Cell - drug therapy</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Cell Culture Techniques</topic><topic>Cell Death - drug effects</topic><topic>Cell Death - genetics</topic><topic>Cell Hypoxia - physiology</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cell Survival - drug effects</topic><topic>cisplatin (CDDP)</topic><topic>Cisplatin - therapeutic use</topic><topic>Dentistry</topic><topic>Drug Resistance, Neoplasm - drug effects</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Gene Expression Profiling</topic><topic>Gene Knockdown Techniques</topic><topic>Gene Silencing</topic><topic>Glucose Transporter Type 1 - genetics</topic><topic>glucose transporter-1(GLUT-1)</topic><topic>Humans</topic><topic>hypoxia</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - genetics</topic><topic>Mouth Neoplasms - drug therapy</topic><topic>Mouth Neoplasms - genetics</topic><topic>Mouth Neoplasms - pathology</topic><topic>oral squamous cell carcinoma</topic><topic>RNA, Small Interfering - genetics</topic><topic>Tongue Neoplasms - drug therapy</topic><topic>Tongue Neoplasms - pathology</topic><topic>Tumor Microenvironment - drug effects</topic><topic>Tumor Microenvironment - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shimanishi, Makoto</creatorcontrib><creatorcontrib>Ogi, Kazuhiro</creatorcontrib><creatorcontrib>Sogabe, Yohei</creatorcontrib><creatorcontrib>Kaneko, Takeshi</creatorcontrib><creatorcontrib>Dehari, Hironari</creatorcontrib><creatorcontrib>Miyazaki, Akihiro</creatorcontrib><creatorcontrib>Hiratsuka, Hiroyoshi</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of oral pathology & medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shimanishi, Makoto</au><au>Ogi, Kazuhiro</au><au>Sogabe, Yohei</au><au>Kaneko, Takeshi</au><au>Dehari, Hironari</au><au>Miyazaki, Akihiro</au><au>Hiratsuka, Hiroyoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Silencing of GLUT-1 inhibits sensitization of oral cancer cells to cisplatin during hypoxia</atitle><jtitle>Journal of oral pathology & medicine</jtitle><addtitle>J Oral Pathol Med</addtitle><date>2013-05</date><risdate>2013</risdate><volume>42</volume><issue>5</issue><spage>382</spage><epage>388</epage><pages>382-388</pages><issn>0904-2512</issn><eissn>1600-0714</eissn><abstract>Background
During tumor development, cells are exposed to a hypoxic microenvironment. Tumor hypoxia also has a profound influence on the sensitivity of cancer chemotherapy.
The objective of this study was to investigate the mechanism of cisplatin (CDDP) resistance of oral squamous cell carcinoma (OSCC) cells under hypoxia by analyzing gene expression profiles to identify key genes and factors involved.
Methods
Cell viability was measured following culture of the cells in the presence or absence of CDDP, under normoxic or hypoxic conditions, using a CCK‐8 assay. Analysis of the expression of HIF target genes in hypoxia‐treated cells was performed using an HIF‐regulated cDNA plate array. Changes in the mRNA expression of selected HIF target genes were analyzed using RT‐PCR, and changes in the protein levels of these genes were analyzed by Western blotting. Tumor cell apoptosis was assessed by flow cytometry.
Results
The OSCC cell lines responded differently to CDDP under normoxic and hypoxic conditions. The expression of glucose transporter protein‐1 (GLUT‐1) was up‐regulated in human squamous cell carcinoma of mouth (HSC‐2) cells under hypoxia. Furthermore, there was little correlation between the cisplatin sensitivity of human squamous cell carcinoma of tongue (SAS) in normoxia and hypoxia. After GLUT‐1 knockdown, CDDP treatment resulted in increased rates of apoptosis under hypoxia as compared with normoxia in cell lines HSC‐2, Ca9‐22, and SAS (P = 0.025).
Conclusion
The results of this study suggest that knockdown of GLUT‐1 inhibits sensitization of oral squamous cells to CDDP during hypoxia in HSC‐2, Ca9‐22, and SAS cells.</abstract><cop>Denmark</cop><pub>Blackwell Publishing Ltd</pub><pmid>23227892</pmid><doi>10.1111/jop.12028</doi><tpages>7</tpages></addata></record> |
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| subjects | Antineoplastic Agents - therapeutic use Apoptosis - drug effects Basic Helix-Loop-Helix Transcription Factors - genetics Carcinoma, Squamous Cell - drug therapy Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - pathology Cell Culture Techniques Cell Death - drug effects Cell Death - genetics Cell Hypoxia - physiology Cell Line, Tumor Cell Proliferation Cell Survival - drug effects cisplatin (CDDP) Cisplatin - therapeutic use Dentistry Drug Resistance, Neoplasm - drug effects Drug Resistance, Neoplasm - genetics Gene Expression Profiling Gene Knockdown Techniques Gene Silencing Glucose Transporter Type 1 - genetics glucose transporter-1(GLUT-1) Humans hypoxia Hypoxia-Inducible Factor 1, alpha Subunit - genetics Mouth Neoplasms - drug therapy Mouth Neoplasms - genetics Mouth Neoplasms - pathology oral squamous cell carcinoma RNA, Small Interfering - genetics Tongue Neoplasms - drug therapy Tongue Neoplasms - pathology Tumor Microenvironment - drug effects Tumor Microenvironment - genetics |
| title | Silencing of GLUT-1 inhibits sensitization of oral cancer cells to cisplatin during hypoxia |
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