Interleukin-11 Increases Cell Motility and Up-Regulates Intercellular Adhesion Molecule-1 Expression in Human Chondrosarcoma Cells

Interleukin‐11 (IL‐11) was originally identified as the cytokine that could induce the proliferation of human cells. Recent studies have shown that IL‐11 plays a critical role in tumor growth, angiogenesis, and metastasis. Chondrosarcoma is a type of highly malignant tumor with a potent capacity to...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of cellular biochemistry 2012-11, Vol.113 (11), p.3353-3362
Hauptverfasser: Li, Te-Mao, Wu, Chi-Ming, Huang, Hsin-Chih, Chou, Pei-Chi, Fong, Yi-Chin, Tang, Chih-Hsin
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 3362
container_issue 11
container_start_page 3353
container_title Journal of cellular biochemistry
container_volume 113
creator Li, Te-Mao
Wu, Chi-Ming
Huang, Hsin-Chih
Chou, Pei-Chi
Fong, Yi-Chin
Tang, Chih-Hsin
description Interleukin‐11 (IL‐11) was originally identified as the cytokine that could induce the proliferation of human cells. Recent studies have shown that IL‐11 plays a critical role in tumor growth, angiogenesis, and metastasis. Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. However, the effects of IL‐11 on human chondrosarcoma cells are largely unknown. Here, we found that IL‐11 increased the migration and expression of intercellular adhesion molecule‐1 (ICAM)‐1 in human chondrosarcoma cells. We also found that human chondrosarcoma tissues had significant expression of the IL‐11 which was higher than that in primary chondrocytes. The phosphatidylinositol 3‐kinase (PI3K), Akt, and NF‐κB pathways were activated by IL‐11 treatment, and the IL‐11‐induced expression of ICAM‐1 and migration activity were inhibited by the specific inhibitors and mutant forms of PI3K, Akt, and NF‐κB cascades. Taken together, our results indicate that IL‐11 enhanced the migration of the chondrosarcoma cells by increasing ICAM‐1 expression through the IL‐11Rα receptor, PI3K, Akt, and NF‐κB signal transduction pathway. J. Cell. Biochem. 113: 3353–3362, 2012. © 2012 Wiley Periodicals, Inc.
doi_str_mv 10.1002/jcb.24211
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1458536164</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1458536164</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4991-eaf3fd5e384499133d74ce4a1b828b03208a7b9b9c24e7b33dd56721c256cb8a3</originalsourceid><addsrcrecordid>eNqFkc1u1DAUhS0EotPCghdAltjQhVv_xsmyhNIOKgVVVEhsLMe5Qz1NnMFORGfLk-OZabtAQqys6_udc3V0EHrF6BGjlB8vXXPEJWfsCZoxWmkiCymfohnVghIuGN9D-yktKaVVJfhztMd5BspCzNDveRghdjDd-kAYw_PgItgECdfQdfjTMPrOj2tsQ4uvV-QKfkydHfN6q3OZyXPEJ-0NJD-ELOjATR0Qhk_vVhHS9tcHfD71NuD6ZghtHJKNbujt9kZ6gZ4tbJfg5f17gK4_nH6tz8nF57N5fXJBnKwqRsAuxKJVIEq5mYVotXQgLWtKXjZUcFpa3VRN5bgE3eR9qwrNmeOqcE1pxQF6u_NdxeHnBGk0vU-bBDbAMCXDpCqVKFgh_49SyQRXtGAZffMXuhymGHIQkxEuhS5UlanDHeVy-BRhYVbR9zaus5XZdGhyh2bbYWZf3ztOTQ_tI_lQWgaOd8Av38H6307mY_3uwZLsFD6NcPeosPHWFFpoZb5dnhldqavL999L80X8AX5js9g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1322437659</pqid></control><display><type>article</type><title>Interleukin-11 Increases Cell Motility and Up-Regulates Intercellular Adhesion Molecule-1 Expression in Human Chondrosarcoma Cells</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Li, Te-Mao ; Wu, Chi-Ming ; Huang, Hsin-Chih ; Chou, Pei-Chi ; Fong, Yi-Chin ; Tang, Chih-Hsin</creator><creatorcontrib>Li, Te-Mao ; Wu, Chi-Ming ; Huang, Hsin-Chih ; Chou, Pei-Chi ; Fong, Yi-Chin ; Tang, Chih-Hsin</creatorcontrib><description>Interleukin‐11 (IL‐11) was originally identified as the cytokine that could induce the proliferation of human cells. Recent studies have shown that IL‐11 plays a critical role in tumor growth, angiogenesis, and metastasis. Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. However, the effects of IL‐11 on human chondrosarcoma cells are largely unknown. Here, we found that IL‐11 increased the migration and expression of intercellular adhesion molecule‐1 (ICAM)‐1 in human chondrosarcoma cells. We also found that human chondrosarcoma tissues had significant expression of the IL‐11 which was higher than that in primary chondrocytes. The phosphatidylinositol 3‐kinase (PI3K), Akt, and NF‐κB pathways were activated by IL‐11 treatment, and the IL‐11‐induced expression of ICAM‐1 and migration activity were inhibited by the specific inhibitors and mutant forms of PI3K, Akt, and NF‐κB cascades. Taken together, our results indicate that IL‐11 enhanced the migration of the chondrosarcoma cells by increasing ICAM‐1 expression through the IL‐11Rα receptor, PI3K, Akt, and NF‐κB signal transduction pathway. J. Cell. Biochem. 113: 3353–3362, 2012. © 2012 Wiley Periodicals, Inc.</description><identifier>ISSN: 0730-2312</identifier><identifier>EISSN: 1097-4644</identifier><identifier>DOI: 10.1002/jcb.24211</identifier><identifier>PMID: 22644863</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Bone Neoplasms - genetics ; Bone Neoplasms - metabolism ; Bone Neoplasms - pathology ; Case-Control Studies ; Cell Movement - drug effects ; Chondrocytes - cytology ; Chondrocytes - metabolism ; CHONDROSARCOMA ; Chondrosarcoma - genetics ; Chondrosarcoma - metabolism ; Chondrosarcoma - pathology ; Enzyme Inhibitors - pharmacology ; Humans ; ICAM-1 ; IL-11 ; Intercellular Adhesion Molecule-1 - genetics ; Intercellular Adhesion Molecule-1 - metabolism ; Interleukin-11 - antagonists &amp; inhibitors ; Interleukin-11 - genetics ; Interleukin-11 Receptor alpha Subunit - genetics ; Interleukin-11 Receptor alpha Subunit - metabolism ; MIGRATION ; NF-kappa B - genetics ; NF-kappa B - metabolism ; Phosphatidylinositol 3-Kinase - genetics ; Phosphatidylinositol 3-Kinase - metabolism ; Proto-Oncogene Proteins c-akt - genetics ; Proto-Oncogene Proteins c-akt - metabolism ; RNA, Small Interfering - genetics ; Signal Transduction - drug effects ; Tumor Cells, Cultured ; Up-Regulation - drug effects</subject><ispartof>Journal of cellular biochemistry, 2012-11, Vol.113 (11), p.3353-3362</ispartof><rights>Copyright © 2012 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4991-eaf3fd5e384499133d74ce4a1b828b03208a7b9b9c24e7b33dd56721c256cb8a3</citedby><cites>FETCH-LOGICAL-c4991-eaf3fd5e384499133d74ce4a1b828b03208a7b9b9c24e7b33dd56721c256cb8a3</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%2Fjcb.24211$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcb.24211$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22644863$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Te-Mao</creatorcontrib><creatorcontrib>Wu, Chi-Ming</creatorcontrib><creatorcontrib>Huang, Hsin-Chih</creatorcontrib><creatorcontrib>Chou, Pei-Chi</creatorcontrib><creatorcontrib>Fong, Yi-Chin</creatorcontrib><creatorcontrib>Tang, Chih-Hsin</creatorcontrib><title>Interleukin-11 Increases Cell Motility and Up-Regulates Intercellular Adhesion Molecule-1 Expression in Human Chondrosarcoma Cells</title><title>Journal of cellular biochemistry</title><addtitle>J. Cell. Biochem</addtitle><description>Interleukin‐11 (IL‐11) was originally identified as the cytokine that could induce the proliferation of human cells. Recent studies have shown that IL‐11 plays a critical role in tumor growth, angiogenesis, and metastasis. Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. However, the effects of IL‐11 on human chondrosarcoma cells are largely unknown. Here, we found that IL‐11 increased the migration and expression of intercellular adhesion molecule‐1 (ICAM)‐1 in human chondrosarcoma cells. We also found that human chondrosarcoma tissues had significant expression of the IL‐11 which was higher than that in primary chondrocytes. The phosphatidylinositol 3‐kinase (PI3K), Akt, and NF‐κB pathways were activated by IL‐11 treatment, and the IL‐11‐induced expression of ICAM‐1 and migration activity were inhibited by the specific inhibitors and mutant forms of PI3K, Akt, and NF‐κB cascades. Taken together, our results indicate that IL‐11 enhanced the migration of the chondrosarcoma cells by increasing ICAM‐1 expression through the IL‐11Rα receptor, PI3K, Akt, and NF‐κB signal transduction pathway. J. Cell. Biochem. 113: 3353–3362, 2012. © 2012 Wiley Periodicals, Inc.</description><subject>Bone Neoplasms - genetics</subject><subject>Bone Neoplasms - metabolism</subject><subject>Bone Neoplasms - pathology</subject><subject>Case-Control Studies</subject><subject>Cell Movement - drug effects</subject><subject>Chondrocytes - cytology</subject><subject>Chondrocytes - metabolism</subject><subject>CHONDROSARCOMA</subject><subject>Chondrosarcoma - genetics</subject><subject>Chondrosarcoma - metabolism</subject><subject>Chondrosarcoma - pathology</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Humans</subject><subject>ICAM-1</subject><subject>IL-11</subject><subject>Intercellular Adhesion Molecule-1 - genetics</subject><subject>Intercellular Adhesion Molecule-1 - metabolism</subject><subject>Interleukin-11 - antagonists &amp; inhibitors</subject><subject>Interleukin-11 - genetics</subject><subject>Interleukin-11 Receptor alpha Subunit - genetics</subject><subject>Interleukin-11 Receptor alpha Subunit - metabolism</subject><subject>MIGRATION</subject><subject>NF-kappa B - genetics</subject><subject>NF-kappa B - metabolism</subject><subject>Phosphatidylinositol 3-Kinase - genetics</subject><subject>Phosphatidylinositol 3-Kinase - metabolism</subject><subject>Proto-Oncogene Proteins c-akt - genetics</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>RNA, Small Interfering - genetics</subject><subject>Signal Transduction - drug effects</subject><subject>Tumor Cells, Cultured</subject><subject>Up-Regulation - drug effects</subject><issn>0730-2312</issn><issn>1097-4644</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAUhS0EotPCghdAltjQhVv_xsmyhNIOKgVVVEhsLMe5Qz1NnMFORGfLk-OZabtAQqys6_udc3V0EHrF6BGjlB8vXXPEJWfsCZoxWmkiCymfohnVghIuGN9D-yktKaVVJfhztMd5BspCzNDveRghdjDd-kAYw_PgItgECdfQdfjTMPrOj2tsQ4uvV-QKfkydHfN6q3OZyXPEJ-0NJD-ELOjATR0Qhk_vVhHS9tcHfD71NuD6ZghtHJKNbujt9kZ6gZ4tbJfg5f17gK4_nH6tz8nF57N5fXJBnKwqRsAuxKJVIEq5mYVotXQgLWtKXjZUcFpa3VRN5bgE3eR9qwrNmeOqcE1pxQF6u_NdxeHnBGk0vU-bBDbAMCXDpCqVKFgh_49SyQRXtGAZffMXuhymGHIQkxEuhS5UlanDHeVy-BRhYVbR9zaus5XZdGhyh2bbYWZf3ztOTQ_tI_lQWgaOd8Av38H6307mY_3uwZLsFD6NcPeosPHWFFpoZb5dnhldqavL999L80X8AX5js9g</recordid><startdate>201211</startdate><enddate>201211</enddate><creator>Li, Te-Mao</creator><creator>Wu, Chi-Ming</creator><creator>Huang, Hsin-Chih</creator><creator>Chou, Pei-Chi</creator><creator>Fong, Yi-Chin</creator><creator>Tang, Chih-Hsin</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley Subscription Services, Inc</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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T7</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201211</creationdate><title>Interleukin-11 Increases Cell Motility and Up-Regulates Intercellular Adhesion Molecule-1 Expression in Human Chondrosarcoma Cells</title><author>Li, Te-Mao ; Wu, Chi-Ming ; Huang, Hsin-Chih ; Chou, Pei-Chi ; Fong, Yi-Chin ; Tang, Chih-Hsin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4991-eaf3fd5e384499133d74ce4a1b828b03208a7b9b9c24e7b33dd56721c256cb8a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Bone Neoplasms - genetics</topic><topic>Bone Neoplasms - metabolism</topic><topic>Bone Neoplasms - pathology</topic><topic>Case-Control Studies</topic><topic>Cell Movement - drug effects</topic><topic>Chondrocytes - cytology</topic><topic>Chondrocytes - metabolism</topic><topic>CHONDROSARCOMA</topic><topic>Chondrosarcoma - genetics</topic><topic>Chondrosarcoma - metabolism</topic><topic>Chondrosarcoma - pathology</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Humans</topic><topic>ICAM-1</topic><topic>IL-11</topic><topic>Intercellular Adhesion Molecule-1 - genetics</topic><topic>Intercellular Adhesion Molecule-1 - metabolism</topic><topic>Interleukin-11 - antagonists &amp; inhibitors</topic><topic>Interleukin-11 - genetics</topic><topic>Interleukin-11 Receptor alpha Subunit - genetics</topic><topic>Interleukin-11 Receptor alpha Subunit - metabolism</topic><topic>MIGRATION</topic><topic>NF-kappa B - genetics</topic><topic>NF-kappa B - metabolism</topic><topic>Phosphatidylinositol 3-Kinase - genetics</topic><topic>Phosphatidylinositol 3-Kinase - metabolism</topic><topic>Proto-Oncogene Proteins c-akt - genetics</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>RNA, Small Interfering - genetics</topic><topic>Signal Transduction - drug effects</topic><topic>Tumor Cells, Cultured</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Te-Mao</creatorcontrib><creatorcontrib>Wu, Chi-Ming</creatorcontrib><creatorcontrib>Huang, Hsin-Chih</creatorcontrib><creatorcontrib>Chou, Pei-Chi</creatorcontrib><creatorcontrib>Fong, Yi-Chin</creatorcontrib><creatorcontrib>Tang, Chih-Hsin</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>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cellular biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Te-Mao</au><au>Wu, Chi-Ming</au><au>Huang, Hsin-Chih</au><au>Chou, Pei-Chi</au><au>Fong, Yi-Chin</au><au>Tang, Chih-Hsin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interleukin-11 Increases Cell Motility and Up-Regulates Intercellular Adhesion Molecule-1 Expression in Human Chondrosarcoma Cells</atitle><jtitle>Journal of cellular biochemistry</jtitle><addtitle>J. Cell. Biochem</addtitle><date>2012-11</date><risdate>2012</risdate><volume>113</volume><issue>11</issue><spage>3353</spage><epage>3362</epage><pages>3353-3362</pages><issn>0730-2312</issn><eissn>1097-4644</eissn><abstract>Interleukin‐11 (IL‐11) was originally identified as the cytokine that could induce the proliferation of human cells. Recent studies have shown that IL‐11 plays a critical role in tumor growth, angiogenesis, and metastasis. Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. However, the effects of IL‐11 on human chondrosarcoma cells are largely unknown. Here, we found that IL‐11 increased the migration and expression of intercellular adhesion molecule‐1 (ICAM)‐1 in human chondrosarcoma cells. We also found that human chondrosarcoma tissues had significant expression of the IL‐11 which was higher than that in primary chondrocytes. The phosphatidylinositol 3‐kinase (PI3K), Akt, and NF‐κB pathways were activated by IL‐11 treatment, and the IL‐11‐induced expression of ICAM‐1 and migration activity were inhibited by the specific inhibitors and mutant forms of PI3K, Akt, and NF‐κB cascades. Taken together, our results indicate that IL‐11 enhanced the migration of the chondrosarcoma cells by increasing ICAM‐1 expression through the IL‐11Rα receptor, PI3K, Akt, and NF‐κB signal transduction pathway. J. Cell. Biochem. 113: 3353–3362, 2012. © 2012 Wiley Periodicals, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>22644863</pmid><doi>10.1002/jcb.24211</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0730-2312
ispartof Journal of cellular biochemistry, 2012-11, Vol.113 (11), p.3353-3362
issn 0730-2312
1097-4644
language eng
recordid cdi_proquest_miscellaneous_1458536164
source MEDLINE; Wiley Online Library Journals Frontfile Complete
subjects Bone Neoplasms - genetics
Bone Neoplasms - metabolism
Bone Neoplasms - pathology
Case-Control Studies
Cell Movement - drug effects
Chondrocytes - cytology
Chondrocytes - metabolism
CHONDROSARCOMA
Chondrosarcoma - genetics
Chondrosarcoma - metabolism
Chondrosarcoma - pathology
Enzyme Inhibitors - pharmacology
Humans
ICAM-1
IL-11
Intercellular Adhesion Molecule-1 - genetics
Intercellular Adhesion Molecule-1 - metabolism
Interleukin-11 - antagonists & inhibitors
Interleukin-11 - genetics
Interleukin-11 Receptor alpha Subunit - genetics
Interleukin-11 Receptor alpha Subunit - metabolism
MIGRATION
NF-kappa B - genetics
NF-kappa B - metabolism
Phosphatidylinositol 3-Kinase - genetics
Phosphatidylinositol 3-Kinase - metabolism
Proto-Oncogene Proteins c-akt - genetics
Proto-Oncogene Proteins c-akt - metabolism
RNA, Small Interfering - genetics
Signal Transduction - drug effects
Tumor Cells, Cultured
Up-Regulation - drug effects
title Interleukin-11 Increases Cell Motility and Up-Regulates Intercellular Adhesion Molecule-1 Expression in Human Chondrosarcoma Cells
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T11%3A53%3A07IST&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=Interleukin-11%20Increases%20Cell%20Motility%20and%20Up-Regulates%20Intercellular%20Adhesion%20Molecule-1%20Expression%20in%20Human%20Chondrosarcoma%20Cells&rft.jtitle=Journal%20of%20cellular%20biochemistry&rft.au=Li,%20Te-Mao&rft.date=2012-11&rft.volume=113&rft.issue=11&rft.spage=3353&rft.epage=3362&rft.pages=3353-3362&rft.issn=0730-2312&rft.eissn=1097-4644&rft_id=info:doi/10.1002/jcb.24211&rft_dat=%3Cproquest_cross%3E1458536164%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=1322437659&rft_id=info:pmid/22644863&rfr_iscdi=true