XIAP expression is post-transcriptionally upregulated in childhood ALL and is associated with glucocorticoid response in T-cell ALL
Background Resistance to glucocorticoid induced apoptosis is one of the major risk factors for relapse and poor outcome in childhood acute lymphoblastic leukemia (ALL). Overexpression of X‐linked inhibitor of apoptosis protein (XIAP) has been shown to be associated with chemotherapy resistance in se...
Gespeichert in:
| Veröffentlicht in: | Pediatric blood & cancer 2010-08, Vol.55 (2), p.260-266 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 266 |
|---|---|
| container_issue | 2 |
| container_start_page | 260 |
| container_title | Pediatric blood & cancer |
| container_volume | 55 |
| creator | Hundsdoerfer, Patrick Dietrich, Isabell Schmelz, Karin Eckert, Cornelia Henze, Günter |
| description | Background
Resistance to glucocorticoid induced apoptosis is one of the major risk factors for relapse and poor outcome in childhood acute lymphoblastic leukemia (ALL). Overexpression of X‐linked inhibitor of apoptosis protein (XIAP) has been shown to be associated with chemotherapy resistance in several malignancies.
Procedure
XIAP protein and mRNA expression were determined in leukemic blasts of 51 childhood ALL patients and normal bone marrow mononuclear cells. XIAP expression was correlated with glucocorticoid response and outcome.
Results
XIAP protein but not mRNA expression was found to be highly increased in childhood ALL compared to control bone marrow mononuclear cells (MNC) (median: 3.5 vs. 0.14 ng/105 MNC, P |
| doi_str_mv | 10.1002/pbc.22541 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_733570255</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1020840381</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3951-f5ec717665c4ce33bf2a22b23c7a3eab64e5c6bdb7a34585fbb4f4eade34f56e3</originalsourceid><addsrcrecordid>eNp9kU9v0zAYhy0EYmNw4Asg34BDNv9N2mNX0TIpgh6GmLhYtvNmNbhxsBNtPfPFcdatNzi9tvU8v9fSD6G3lJxTQthFb-w5Y1LQZ-iUSiELSWj1_Hgm8xP0KqWfGS2JnL1EJywPNpflKfpzc7XYYLjvI6TkQoddwn1IQzFE3SUbXT_kV-39Ho-ZuR29HqDBrsN263yzDaHBi7rGumsmVacUrHtA7tywxbd-tMGGODgbXIPzkj50CSb_urDg_SS_Ri9a7RO8eZxn6Nvq0_Xyc1F_XV8tF3Vh-VzSopVgK1qVpbTCAuemZZoxw7itNAdtSgHSlqYx-SrkTLbGiFaAboCLVpbAz9D7Q24fw-8R0qB2Lk2f0B2EMamKc1kRJmUmP_yXpISRmSB8RjP68YDaGFKK0Ko-up2O-wypqR2V21EP7WT23WPsaHbQHMmnOjJwcQDunIf9v5PU5nL5FFkcDJcGuD8aOv5SZcUrqb5_Wav6x4pu1jcrdcn_AlfDqms</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1020840381</pqid></control><display><type>article</type><title>XIAP expression is post-transcriptionally upregulated in childhood ALL and is associated with glucocorticoid response in T-cell ALL</title><source>MEDLINE</source><source>Wiley Journals</source><creator>Hundsdoerfer, Patrick ; Dietrich, Isabell ; Schmelz, Karin ; Eckert, Cornelia ; Henze, Günter</creator><creatorcontrib>Hundsdoerfer, Patrick ; Dietrich, Isabell ; Schmelz, Karin ; Eckert, Cornelia ; Henze, Günter</creatorcontrib><description>Background
Resistance to glucocorticoid induced apoptosis is one of the major risk factors for relapse and poor outcome in childhood acute lymphoblastic leukemia (ALL). Overexpression of X‐linked inhibitor of apoptosis protein (XIAP) has been shown to be associated with chemotherapy resistance in several malignancies.
Procedure
XIAP protein and mRNA expression were determined in leukemic blasts of 51 childhood ALL patients and normal bone marrow mononuclear cells. XIAP expression was correlated with glucocorticoid response and outcome.
Results
XIAP protein but not mRNA expression was found to be highly increased in childhood ALL compared to control bone marrow mononuclear cells (MNC) (median: 3.5 vs. 0.14 ng/105 MNC, P < 0.0001) indicating a post‐transcriptional regulation of XIAP expression. In patients with T‐cell ALL, poor prednisone response was associated with increased XIAP expression (median: 2.8 in good vs. 5.8 in poor responders; P = 0.005). Similarly, T‐cell ALL patients suffering adverse events showed higher initial XIAP levels than patients in continuous complete remission (CCR) (median: 2.7 in patients in CCR vs. 5.6 in patients suffering adverse events; P = 0.007). XIAP inhibition using the low‐molecular‐weight SMAC mimetic LBW242 resulted in a significant increase of prednisone‐induced apoptosis in vitro.
Conclusion
In childhood ALL compared to control bone marrow, the expression of the apoptosis inhibitor XIAP is highly increased by post‐transcriptional regulation. The association with poor in vivo glucocorticoid response and outcome in T‐cell ALL suggests XIAP inhibition as a promising novel approach for the treatment of resistant ALL. Pediatr Blood Cancer. 2010;55:260–266. © 2010 Wiley–Liss, Inc.</description><identifier>ISSN: 1545-5009</identifier><identifier>ISSN: 1545-5017</identifier><identifier>EISSN: 1545-5017</identifier><identifier>DOI: 10.1002/pbc.22541</identifier><identifier>PMID: 20582956</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Acute lymphatic leukemia ; Adult ; ALL ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Apoptosis ; Blast ; Blood ; Bone marrow ; Bone Marrow Cells - pathology ; Bone Marrow Examination ; Cancer ; Chemotherapy ; Child ; Children ; DIABLO protein ; Drug Resistance ; Female ; Gene expression ; Gene Expression Regulation, Leukemic ; Glucocorticoids ; Glucocorticoids - pharmacology ; Glucocorticoids - therapeutic use ; Humans ; Leukemia-Lymphoma, Adult T-Cell - drug therapy ; Leukocytes (mononuclear) ; Lymphocytes T ; Male ; Malignancy ; molecular biology ; molecular diagnosis & therapy ; Monocytes - pathology ; pediatric hematology/oncology ; Pharmacogenetics ; Post-transcription ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology ; Prednisone ; Prognosis ; Remission ; Risk factors ; RNA, Messenger - analysis ; Treatment Outcome ; Up-Regulation ; X chromosome ; X-Linked Inhibitor of Apoptosis Protein - analysis ; X-Linked Inhibitor of Apoptosis Protein - genetics ; XIAP protein</subject><ispartof>Pediatric blood & cancer, 2010-08, Vol.55 (2), p.260-266</ispartof><rights>Copyright © 2010 Wiley‐Liss, Inc.</rights><rights>(c) 2010 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3951-f5ec717665c4ce33bf2a22b23c7a3eab64e5c6bdb7a34585fbb4f4eade34f56e3</citedby><cites>FETCH-LOGICAL-c3951-f5ec717665c4ce33bf2a22b23c7a3eab64e5c6bdb7a34585fbb4f4eade34f56e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpbc.22541$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpbc.22541$$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/20582956$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hundsdoerfer, Patrick</creatorcontrib><creatorcontrib>Dietrich, Isabell</creatorcontrib><creatorcontrib>Schmelz, Karin</creatorcontrib><creatorcontrib>Eckert, Cornelia</creatorcontrib><creatorcontrib>Henze, Günter</creatorcontrib><title>XIAP expression is post-transcriptionally upregulated in childhood ALL and is associated with glucocorticoid response in T-cell ALL</title><title>Pediatric blood & cancer</title><addtitle>Pediatr. Blood Cancer</addtitle><description>Background
Resistance to glucocorticoid induced apoptosis is one of the major risk factors for relapse and poor outcome in childhood acute lymphoblastic leukemia (ALL). Overexpression of X‐linked inhibitor of apoptosis protein (XIAP) has been shown to be associated with chemotherapy resistance in several malignancies.
Procedure
XIAP protein and mRNA expression were determined in leukemic blasts of 51 childhood ALL patients and normal bone marrow mononuclear cells. XIAP expression was correlated with glucocorticoid response and outcome.
Results
XIAP protein but not mRNA expression was found to be highly increased in childhood ALL compared to control bone marrow mononuclear cells (MNC) (median: 3.5 vs. 0.14 ng/105 MNC, P < 0.0001) indicating a post‐transcriptional regulation of XIAP expression. In patients with T‐cell ALL, poor prednisone response was associated with increased XIAP expression (median: 2.8 in good vs. 5.8 in poor responders; P = 0.005). Similarly, T‐cell ALL patients suffering adverse events showed higher initial XIAP levels than patients in continuous complete remission (CCR) (median: 2.7 in patients in CCR vs. 5.6 in patients suffering adverse events; P = 0.007). XIAP inhibition using the low‐molecular‐weight SMAC mimetic LBW242 resulted in a significant increase of prednisone‐induced apoptosis in vitro.
Conclusion
In childhood ALL compared to control bone marrow, the expression of the apoptosis inhibitor XIAP is highly increased by post‐transcriptional regulation. The association with poor in vivo glucocorticoid response and outcome in T‐cell ALL suggests XIAP inhibition as a promising novel approach for the treatment of resistant ALL. Pediatr Blood Cancer. 2010;55:260–266. © 2010 Wiley–Liss, Inc.</description><subject>Acute lymphatic leukemia</subject><subject>Adult</subject><subject>ALL</subject><subject>Antineoplastic Combined Chemotherapy Protocols - pharmacology</subject><subject>Apoptosis</subject><subject>Blast</subject><subject>Blood</subject><subject>Bone marrow</subject><subject>Bone Marrow Cells - pathology</subject><subject>Bone Marrow Examination</subject><subject>Cancer</subject><subject>Chemotherapy</subject><subject>Child</subject><subject>Children</subject><subject>DIABLO protein</subject><subject>Drug Resistance</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Leukemic</subject><subject>Glucocorticoids</subject><subject>Glucocorticoids - pharmacology</subject><subject>Glucocorticoids - therapeutic use</subject><subject>Humans</subject><subject>Leukemia-Lymphoma, Adult T-Cell - drug therapy</subject><subject>Leukocytes (mononuclear)</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Malignancy</subject><subject>molecular biology</subject><subject>molecular diagnosis & therapy</subject><subject>Monocytes - pathology</subject><subject>pediatric hematology/oncology</subject><subject>Pharmacogenetics</subject><subject>Post-transcription</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology</subject><subject>Prednisone</subject><subject>Prognosis</subject><subject>Remission</subject><subject>Risk factors</subject><subject>RNA, Messenger - analysis</subject><subject>Treatment Outcome</subject><subject>Up-Regulation</subject><subject>X chromosome</subject><subject>X-Linked Inhibitor of Apoptosis Protein - analysis</subject><subject>X-Linked Inhibitor of Apoptosis Protein - genetics</subject><subject>XIAP protein</subject><issn>1545-5009</issn><issn>1545-5017</issn><issn>1545-5017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9v0zAYhy0EYmNw4Asg34BDNv9N2mNX0TIpgh6GmLhYtvNmNbhxsBNtPfPFcdatNzi9tvU8v9fSD6G3lJxTQthFb-w5Y1LQZ-iUSiELSWj1_Hgm8xP0KqWfGS2JnL1EJywPNpflKfpzc7XYYLjvI6TkQoddwn1IQzFE3SUbXT_kV-39Ho-ZuR29HqDBrsN263yzDaHBi7rGumsmVacUrHtA7tywxbd-tMGGODgbXIPzkj50CSb_urDg_SS_Ri9a7RO8eZxn6Nvq0_Xyc1F_XV8tF3Vh-VzSopVgK1qVpbTCAuemZZoxw7itNAdtSgHSlqYx-SrkTLbGiFaAboCLVpbAz9D7Q24fw-8R0qB2Lk2f0B2EMamKc1kRJmUmP_yXpISRmSB8RjP68YDaGFKK0Ko-up2O-wypqR2V21EP7WT23WPsaHbQHMmnOjJwcQDunIf9v5PU5nL5FFkcDJcGuD8aOv5SZcUrqb5_Wav6x4pu1jcrdcn_AlfDqms</recordid><startdate>201008</startdate><enddate>201008</enddate><creator>Hundsdoerfer, Patrick</creator><creator>Dietrich, Isabell</creator><creator>Schmelz, Karin</creator><creator>Eckert, Cornelia</creator><creator>Henze, Günter</creator><general>Wiley Subscription Services, Inc., A Wiley Company</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>201008</creationdate><title>XIAP expression is post-transcriptionally upregulated in childhood ALL and is associated with glucocorticoid response in T-cell ALL</title><author>Hundsdoerfer, Patrick ; Dietrich, Isabell ; Schmelz, Karin ; Eckert, Cornelia ; Henze, Günter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3951-f5ec717665c4ce33bf2a22b23c7a3eab64e5c6bdb7a34585fbb4f4eade34f56e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acute lymphatic leukemia</topic><topic>Adult</topic><topic>ALL</topic><topic>Antineoplastic Combined Chemotherapy Protocols - pharmacology</topic><topic>Apoptosis</topic><topic>Blast</topic><topic>Blood</topic><topic>Bone marrow</topic><topic>Bone Marrow Cells - pathology</topic><topic>Bone Marrow Examination</topic><topic>Cancer</topic><topic>Chemotherapy</topic><topic>Child</topic><topic>Children</topic><topic>DIABLO protein</topic><topic>Drug Resistance</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Leukemic</topic><topic>Glucocorticoids</topic><topic>Glucocorticoids - pharmacology</topic><topic>Glucocorticoids - therapeutic use</topic><topic>Humans</topic><topic>Leukemia-Lymphoma, Adult T-Cell - drug therapy</topic><topic>Leukocytes (mononuclear)</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Malignancy</topic><topic>molecular biology</topic><topic>molecular diagnosis & therapy</topic><topic>Monocytes - pathology</topic><topic>pediatric hematology/oncology</topic><topic>Pharmacogenetics</topic><topic>Post-transcription</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology</topic><topic>Prednisone</topic><topic>Prognosis</topic><topic>Remission</topic><topic>Risk factors</topic><topic>RNA, Messenger - analysis</topic><topic>Treatment Outcome</topic><topic>Up-Regulation</topic><topic>X chromosome</topic><topic>X-Linked Inhibitor of Apoptosis Protein - analysis</topic><topic>X-Linked Inhibitor of Apoptosis Protein - genetics</topic><topic>XIAP protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hundsdoerfer, Patrick</creatorcontrib><creatorcontrib>Dietrich, Isabell</creatorcontrib><creatorcontrib>Schmelz, Karin</creatorcontrib><creatorcontrib>Eckert, Cornelia</creatorcontrib><creatorcontrib>Henze, Günter</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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Pediatric blood & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hundsdoerfer, Patrick</au><au>Dietrich, Isabell</au><au>Schmelz, Karin</au><au>Eckert, Cornelia</au><au>Henze, Günter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>XIAP expression is post-transcriptionally upregulated in childhood ALL and is associated with glucocorticoid response in T-cell ALL</atitle><jtitle>Pediatric blood & cancer</jtitle><addtitle>Pediatr. Blood Cancer</addtitle><date>2010-08</date><risdate>2010</risdate><volume>55</volume><issue>2</issue><spage>260</spage><epage>266</epage><pages>260-266</pages><issn>1545-5009</issn><issn>1545-5017</issn><eissn>1545-5017</eissn><abstract>Background
Resistance to glucocorticoid induced apoptosis is one of the major risk factors for relapse and poor outcome in childhood acute lymphoblastic leukemia (ALL). Overexpression of X‐linked inhibitor of apoptosis protein (XIAP) has been shown to be associated with chemotherapy resistance in several malignancies.
Procedure
XIAP protein and mRNA expression were determined in leukemic blasts of 51 childhood ALL patients and normal bone marrow mononuclear cells. XIAP expression was correlated with glucocorticoid response and outcome.
Results
XIAP protein but not mRNA expression was found to be highly increased in childhood ALL compared to control bone marrow mononuclear cells (MNC) (median: 3.5 vs. 0.14 ng/105 MNC, P < 0.0001) indicating a post‐transcriptional regulation of XIAP expression. In patients with T‐cell ALL, poor prednisone response was associated with increased XIAP expression (median: 2.8 in good vs. 5.8 in poor responders; P = 0.005). Similarly, T‐cell ALL patients suffering adverse events showed higher initial XIAP levels than patients in continuous complete remission (CCR) (median: 2.7 in patients in CCR vs. 5.6 in patients suffering adverse events; P = 0.007). XIAP inhibition using the low‐molecular‐weight SMAC mimetic LBW242 resulted in a significant increase of prednisone‐induced apoptosis in vitro.
Conclusion
In childhood ALL compared to control bone marrow, the expression of the apoptosis inhibitor XIAP is highly increased by post‐transcriptional regulation. The association with poor in vivo glucocorticoid response and outcome in T‐cell ALL suggests XIAP inhibition as a promising novel approach for the treatment of resistant ALL. Pediatr Blood Cancer. 2010;55:260–266. © 2010 Wiley–Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>20582956</pmid><doi>10.1002/pbc.22541</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1545-5009 |
| ispartof | Pediatric blood & cancer, 2010-08, Vol.55 (2), p.260-266 |
| issn | 1545-5009 1545-5017 1545-5017 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_733570255 |
| source | MEDLINE; Wiley Journals |
| subjects | Acute lymphatic leukemia Adult ALL Antineoplastic Combined Chemotherapy Protocols - pharmacology Apoptosis Blast Blood Bone marrow Bone Marrow Cells - pathology Bone Marrow Examination Cancer Chemotherapy Child Children DIABLO protein Drug Resistance Female Gene expression Gene Expression Regulation, Leukemic Glucocorticoids Glucocorticoids - pharmacology Glucocorticoids - therapeutic use Humans Leukemia-Lymphoma, Adult T-Cell - drug therapy Leukocytes (mononuclear) Lymphocytes T Male Malignancy molecular biology molecular diagnosis & therapy Monocytes - pathology pediatric hematology/oncology Pharmacogenetics Post-transcription Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology Prednisone Prognosis Remission Risk factors RNA, Messenger - analysis Treatment Outcome Up-Regulation X chromosome X-Linked Inhibitor of Apoptosis Protein - analysis X-Linked Inhibitor of Apoptosis Protein - genetics XIAP protein |
| title | XIAP expression is post-transcriptionally upregulated in childhood ALL and is associated with glucocorticoid response in T-cell ALL |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T11%3A48%3A48IST&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=XIAP%20expression%20is%20post-transcriptionally%20upregulated%20in%20childhood%20ALL%20and%20is%20associated%20with%20glucocorticoid%20response%20in%20T-cell%20ALL&rft.jtitle=Pediatric%20blood%20&%20cancer&rft.au=Hundsdoerfer,%20Patrick&rft.date=2010-08&rft.volume=55&rft.issue=2&rft.spage=260&rft.epage=266&rft.pages=260-266&rft.issn=1545-5009&rft.eissn=1545-5017&rft_id=info:doi/10.1002/pbc.22541&rft_dat=%3Cproquest_cross%3E1020840381%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=1020840381&rft_id=info:pmid/20582956&rfr_iscdi=true |