Systematic review and meta-analysis of temozolomide in animal models of glioma: was clinical efficacy predicted?
Background: Malignant glioma is an aggressive tumour commonly associated with a dismal outcome despite optimal surgical and radio-chemotherapy. Since 2005 temozolomide has been established as first-line chemotherapy. We investigate the role of in vivo glioma models in predicting clinical efficacy. M...
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| Veröffentlicht in: | British journal of cancer 2013-01, Vol.108 (1), p.64-71 |
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| creator | Hirst, T C Vesterinen, H M Sena, E S Egan, K J Macleod, M R Whittle, I R |
| description | Background:
Malignant glioma is an aggressive tumour commonly associated with a dismal outcome despite optimal surgical and radio-chemotherapy. Since 2005 temozolomide has been established as first-line chemotherapy. We investigate the role of
in vivo
glioma models in predicting clinical efficacy.
Methods:
We searched three online databases to systematically identify publications testing temozolomide in animal models of glioma. Median survival and number of animals treated were extracted and quality was assessed using a 12-point scale; random effects meta-analysis was used to estimate efficacy. We analysed the impact of study design and quality and looked for evidence of publication bias.
Results:
We identified 60 publications using temozolomide in models of glioma, comprising 2443 animals. Temozolomide prolonged survival by a factor of 1.88 (95% CI 1.74–2.03) and reduced tumour volume by 50.4% (41.8–58.9) compared with untreated controls. Study design characteristics accounted for a significant proportion of between-study heterogeneity, and there was evidence of a significant publication bias.
Conclusion:
These data reflect those from clinical trials in that temozolomide improves survival and reduces tumour volume, even after accounting for publication bias. Experimental
in vivo
glioma studies of temozolomide differ from those of other glioma therapies in their consistent efficacy and successful translation into clinical medicine. |
| doi_str_mv | 10.1038/bjc.2012.504 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3553514</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2866388141</sourcerecordid><originalsourceid>FETCH-LOGICAL-c546t-aefe704c537d59709249177c7ba16b6195f44baa34b374926858b3632772e8033</originalsourceid><addsrcrecordid>eNptkc1P3DAQxS1UBAvlxrmyVPVGFn_GSQ9UCLWlEhKHtmfLcSaLV0m8tbOg7V_P0F0olXoaWe-nN8_zCDnlbM6ZrM6bpZ8LxsVcM7VHZlxLUfBKmDdkxhgzBasFOyRHOS_xWbPKHJBDIaXgmvMZWX3f5AkGNwVPE9wHeKBubOkAkyvc6PpNDpnGjiITf8c-DqEFGkaEwuB6OsQW-j_Aog9xcB_pg8vU92EMHmXoOpx-Q1cJ2uAnaD-9Jfud6zOc7OYx-fnl84-r6-Lm9uu3q8ubwmtVToWDDgxTXkvT6trgJ1TNjfGmcbxsSl7rTqnGOakaaVQtykpXjSylMEZAxaQ8Jhdb39W6GaD1ME7J9XaVMHfa2OiC_VcZw51dxHsrtZaaKzR4vzNI8dca8mSXcZ3wJNlyUdalLOuKI3W2pXyKOSfoXjZwZp_6sdiPferHYj-Iv3ud6gV-LgSBDzvAZbxgl9zoQ_7LGWYQNcgVWy6jNC4gvUr3v8WPPvOoCw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1269636981</pqid></control><display><type>article</type><title>Systematic review and meta-analysis of temozolomide in animal models of glioma: was clinical efficacy predicted?</title><source>MEDLINE</source><source>SpringerLink Journals</source><source>Nature</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Hirst, T C ; Vesterinen, H M ; Sena, E S ; Egan, K J ; Macleod, M R ; Whittle, I R</creator><creatorcontrib>Hirst, T C ; Vesterinen, H M ; Sena, E S ; Egan, K J ; Macleod, M R ; Whittle, I R</creatorcontrib><description>Background:
Malignant glioma is an aggressive tumour commonly associated with a dismal outcome despite optimal surgical and radio-chemotherapy. Since 2005 temozolomide has been established as first-line chemotherapy. We investigate the role of
in vivo
glioma models in predicting clinical efficacy.
Methods:
We searched three online databases to systematically identify publications testing temozolomide in animal models of glioma. Median survival and number of animals treated were extracted and quality was assessed using a 12-point scale; random effects meta-analysis was used to estimate efficacy. We analysed the impact of study design and quality and looked for evidence of publication bias.
Results:
We identified 60 publications using temozolomide in models of glioma, comprising 2443 animals. Temozolomide prolonged survival by a factor of 1.88 (95% CI 1.74–2.03) and reduced tumour volume by 50.4% (41.8–58.9) compared with untreated controls. Study design characteristics accounted for a significant proportion of between-study heterogeneity, and there was evidence of a significant publication bias.
Conclusion:
These data reflect those from clinical trials in that temozolomide improves survival and reduces tumour volume, even after accounting for publication bias. Experimental
in vivo
glioma studies of temozolomide differ from those of other glioma therapies in their consistent efficacy and successful translation into clinical medicine.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/bjc.2012.504</identifier><identifier>PMID: 23321511</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/92/436/2388 ; 692/308/575 ; 692/699/67/1922 ; Animals ; Antineoplastic Agents, Alkylating - therapeutic use ; Bias ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Brain cancer ; Brain Neoplasms - drug therapy ; Brain research ; Cancer Research ; Cancer therapies ; Chemotherapy ; Clinical trials ; Dacarbazine - analogs & derivatives ; Dacarbazine - therapeutic use ; Disease Models, Animal ; Drug Resistance ; Epidemiology ; Gene therapy ; Glioma - drug therapy ; Medical research ; Medical sciences ; Meta-analysis ; Mice ; Molecular Medicine ; Neurology ; Neurosciences ; Oncology ; Radiation therapy ; Rats ; Survival Analysis ; Systematic review ; Translational Therapeutics ; Treatment Outcome ; Tumors ; Tumors of the nervous system. Phacomatoses ; Xenograft Model Antitumor Assays</subject><ispartof>British journal of cancer, 2013-01, Vol.108 (1), p.64-71</ispartof><rights>The Author(s) 2013</rights><rights>2014 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Jan 15, 2013</rights><rights>Copyright © 2013 Cancer Research UK 2013 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c546t-aefe704c537d59709249177c7ba16b6195f44baa34b374926858b3632772e8033</citedby><cites>FETCH-LOGICAL-c546t-aefe704c537d59709249177c7ba16b6195f44baa34b374926858b3632772e8033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553514/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553514/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27073327$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23321511$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hirst, T C</creatorcontrib><creatorcontrib>Vesterinen, H M</creatorcontrib><creatorcontrib>Sena, E S</creatorcontrib><creatorcontrib>Egan, K J</creatorcontrib><creatorcontrib>Macleod, M R</creatorcontrib><creatorcontrib>Whittle, I R</creatorcontrib><title>Systematic review and meta-analysis of temozolomide in animal models of glioma: was clinical efficacy predicted?</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background:
Malignant glioma is an aggressive tumour commonly associated with a dismal outcome despite optimal surgical and radio-chemotherapy. Since 2005 temozolomide has been established as first-line chemotherapy. We investigate the role of
in vivo
glioma models in predicting clinical efficacy.
Methods:
We searched three online databases to systematically identify publications testing temozolomide in animal models of glioma. Median survival and number of animals treated were extracted and quality was assessed using a 12-point scale; random effects meta-analysis was used to estimate efficacy. We analysed the impact of study design and quality and looked for evidence of publication bias.
Results:
We identified 60 publications using temozolomide in models of glioma, comprising 2443 animals. Temozolomide prolonged survival by a factor of 1.88 (95% CI 1.74–2.03) and reduced tumour volume by 50.4% (41.8–58.9) compared with untreated controls. Study design characteristics accounted for a significant proportion of between-study heterogeneity, and there was evidence of a significant publication bias.
Conclusion:
These data reflect those from clinical trials in that temozolomide improves survival and reduces tumour volume, even after accounting for publication bias. Experimental
in vivo
glioma studies of temozolomide differ from those of other glioma therapies in their consistent efficacy and successful translation into clinical medicine.</description><subject>631/92/436/2388</subject><subject>692/308/575</subject><subject>692/699/67/1922</subject><subject>Animals</subject><subject>Antineoplastic Agents, Alkylating - therapeutic use</subject><subject>Bias</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - drug therapy</subject><subject>Brain research</subject><subject>Cancer Research</subject><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>Clinical trials</subject><subject>Dacarbazine - analogs & derivatives</subject><subject>Dacarbazine - therapeutic use</subject><subject>Disease Models, Animal</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Gene therapy</subject><subject>Glioma - drug therapy</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Meta-analysis</subject><subject>Mice</subject><subject>Molecular Medicine</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Oncology</subject><subject>Radiation therapy</subject><subject>Rats</subject><subject>Survival Analysis</subject><subject>Systematic review</subject><subject>Translational Therapeutics</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>Tumors of the nervous system. Phacomatoses</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkc1P3DAQxS1UBAvlxrmyVPVGFn_GSQ9UCLWlEhKHtmfLcSaLV0m8tbOg7V_P0F0olXoaWe-nN8_zCDnlbM6ZrM6bpZ8LxsVcM7VHZlxLUfBKmDdkxhgzBasFOyRHOS_xWbPKHJBDIaXgmvMZWX3f5AkGNwVPE9wHeKBubOkAkyvc6PpNDpnGjiITf8c-DqEFGkaEwuB6OsQW-j_Aog9xcB_pg8vU92EMHmXoOpx-Q1cJ2uAnaD-9Jfud6zOc7OYx-fnl84-r6-Lm9uu3q8ubwmtVToWDDgxTXkvT6trgJ1TNjfGmcbxsSl7rTqnGOakaaVQtykpXjSylMEZAxaQ8Jhdb39W6GaD1ME7J9XaVMHfa2OiC_VcZw51dxHsrtZaaKzR4vzNI8dca8mSXcZ3wJNlyUdalLOuKI3W2pXyKOSfoXjZwZp_6sdiPferHYj-Iv3ud6gV-LgSBDzvAZbxgl9zoQ_7LGWYQNcgVWy6jNC4gvUr3v8WPPvOoCw</recordid><startdate>20130115</startdate><enddate>20130115</enddate><creator>Hirst, T C</creator><creator>Vesterinen, H M</creator><creator>Sena, E S</creator><creator>Egan, K J</creator><creator>Macleod, M R</creator><creator>Whittle, I R</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20130115</creationdate><title>Systematic review and meta-analysis of temozolomide in animal models of glioma: was clinical efficacy predicted?</title><author>Hirst, T C ; Vesterinen, H M ; Sena, E S ; Egan, K J ; Macleod, M R ; Whittle, I R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c546t-aefe704c537d59709249177c7ba16b6195f44baa34b374926858b3632772e8033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>631/92/436/2388</topic><topic>692/308/575</topic><topic>692/699/67/1922</topic><topic>Animals</topic><topic>Antineoplastic Agents, Alkylating - therapeutic use</topic><topic>Bias</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain cancer</topic><topic>Brain Neoplasms - drug therapy</topic><topic>Brain research</topic><topic>Cancer Research</topic><topic>Cancer therapies</topic><topic>Chemotherapy</topic><topic>Clinical trials</topic><topic>Dacarbazine - analogs & derivatives</topic><topic>Dacarbazine - therapeutic use</topic><topic>Disease Models, Animal</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Gene therapy</topic><topic>Glioma - drug therapy</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Meta-analysis</topic><topic>Mice</topic><topic>Molecular Medicine</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Oncology</topic><topic>Radiation therapy</topic><topic>Rats</topic><topic>Survival Analysis</topic><topic>Systematic review</topic><topic>Translational Therapeutics</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><topic>Tumors of the nervous system. Phacomatoses</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hirst, T C</creatorcontrib><creatorcontrib>Vesterinen, H M</creatorcontrib><creatorcontrib>Sena, E S</creatorcontrib><creatorcontrib>Egan, K J</creatorcontrib><creatorcontrib>Macleod, M R</creatorcontrib><creatorcontrib>Whittle, I R</creatorcontrib><collection>Springer Nature OA Free Journals</collection><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>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hirst, T C</au><au>Vesterinen, H M</au><au>Sena, E S</au><au>Egan, K J</au><au>Macleod, M R</au><au>Whittle, I R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Systematic review and meta-analysis of temozolomide in animal models of glioma: was clinical efficacy predicted?</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2013-01-15</date><risdate>2013</risdate><volume>108</volume><issue>1</issue><spage>64</spage><epage>71</epage><pages>64-71</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Background:
Malignant glioma is an aggressive tumour commonly associated with a dismal outcome despite optimal surgical and radio-chemotherapy. Since 2005 temozolomide has been established as first-line chemotherapy. We investigate the role of
in vivo
glioma models in predicting clinical efficacy.
Methods:
We searched three online databases to systematically identify publications testing temozolomide in animal models of glioma. Median survival and number of animals treated were extracted and quality was assessed using a 12-point scale; random effects meta-analysis was used to estimate efficacy. We analysed the impact of study design and quality and looked for evidence of publication bias.
Results:
We identified 60 publications using temozolomide in models of glioma, comprising 2443 animals. Temozolomide prolonged survival by a factor of 1.88 (95% CI 1.74–2.03) and reduced tumour volume by 50.4% (41.8–58.9) compared with untreated controls. Study design characteristics accounted for a significant proportion of between-study heterogeneity, and there was evidence of a significant publication bias.
Conclusion:
These data reflect those from clinical trials in that temozolomide improves survival and reduces tumour volume, even after accounting for publication bias. Experimental
in vivo
glioma studies of temozolomide differ from those of other glioma therapies in their consistent efficacy and successful translation into clinical medicine.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23321511</pmid><doi>10.1038/bjc.2012.504</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3553514 |
| source | MEDLINE; SpringerLink Journals; Nature; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | 631/92/436/2388 692/308/575 692/699/67/1922 Animals Antineoplastic Agents, Alkylating - therapeutic use Bias Biological and medical sciences Biomedical and Life Sciences Biomedicine Brain cancer Brain Neoplasms - drug therapy Brain research Cancer Research Cancer therapies Chemotherapy Clinical trials Dacarbazine - analogs & derivatives Dacarbazine - therapeutic use Disease Models, Animal Drug Resistance Epidemiology Gene therapy Glioma - drug therapy Medical research Medical sciences Meta-analysis Mice Molecular Medicine Neurology Neurosciences Oncology Radiation therapy Rats Survival Analysis Systematic review Translational Therapeutics Treatment Outcome Tumors Tumors of the nervous system. Phacomatoses Xenograft Model Antitumor Assays |
| title | Systematic review and meta-analysis of temozolomide in animal models of glioma: was clinical efficacy predicted? |
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