Loading…
Clinical and biological significance of Cdk10 in hepatocellular carcinoma
Cyclin-dependent kinase 10 (Cdk10) is a Cdc2-related kinase and plays an essential role in the progression from the G2 to M phase of the cell cycle. However, relative little is known about its expression pattern, clinical relevance, and biological function in hepatocellular carcinoma (HCC). In the p...
Saved in:
| Published in: | Gene 2012-04, Vol.498 (1), p.68-74 |
|---|---|
| Main Authors: | , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c379t-ea37ae747374d5124921e39af288acb519fd04f03c1a002cf692664ad86c8bfc3 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c379t-ea37ae747374d5124921e39af288acb519fd04f03c1a002cf692664ad86c8bfc3 |
| container_end_page | 74 |
| container_issue | 1 |
| container_start_page | 68 |
| container_title | Gene |
| container_volume | 498 |
| creator | Zhong, Xiang-yu Xu, Xiao-xue Yu, Jian-hua Jiang, Gui-xing Yu, Yang Tai, Sheng Wang, Zhi-dong Cui, Yun-fu |
| description | Cyclin-dependent kinase 10 (Cdk10) is a Cdc2-related kinase and plays an essential role in the progression from the G2 to M phase of the cell cycle. However, relative little is known about its expression pattern, clinical relevance, and biological function in hepatocellular carcinoma (HCC). In the present study, we investigated the mRNA and protein expression levels of Cdk10 in 127 pairs of HCC samples and adjacent nontumorous liver tissues and evaluated its clinical significance. Additionally, we assessed the effects of restoration of Cdk10 on cell proliferation and drug sensitivity in HCC cells. We showed that the Cdk10 mRNA and protein expression was markedly decreased in HCC samples compared to adjacent nontumorous liver tissues. Quantitative real-time polymerase chain reaction and immunohistochemical studies revealed that reduced Cdk10 expression was significantly associated with alpha-fetoprotein levels, tumor size, and tumor stage. Ectopic expression of Cdk10 reduced HCC cell proliferation, blocked the cell cycle at the G0-G1 phase, as well as inhibited cell migration and anchorage-independent growth. Additionally, Cdk10 overexpression enhanced the chemosensitivity of HCC cells to cisplatin and epidoxorubicin, two chemotherapeutic agents commonly used in HCC. These data collectively demonstrate that reduced Cdk10 expression is closely linked to HCC development and progression. Restoration of its expression may have therapeutic benefits in treating this malignancy.
► HCC tissues show downregulation of Cdk10. ► Cdk10 reduction correlates with AFP levels, tumor size, and tumor stage in HCC. ► Cdk10 restoration inhibits HCC cell growth and migration. ► Cdk10 overexpression confers chemosensitivity to HCC cells. |
| doi_str_mv | 10.1016/j.gene.2012.01.022 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_927988493</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0378111912000650</els_id><sourcerecordid>927988493</sourcerecordid><originalsourceid>FETCH-LOGICAL-c379t-ea37ae747374d5124921e39af288acb519fd04f03c1a002cf692664ad86c8bfc3</originalsourceid><addsrcrecordid>eNp9kMFOGzEQhi1UBIH2BXqge-tpl7G9u7YlLlXUUiQkDsDZmnjHqcNmHewEibfHaWiP-DIe6Zt_Rh9jXzk0HHh_uWqWNFEjgIsGeANCHLEZ18rUAFJ_YjOQStecc3PKznJeQXldJ07YqRBS9ELBjN3MxzAFh2OF01AtQhzj8m-bw3IKvnwnR1X01Xx44lCFqfpDG9xGR-O4GzFVDpMLU1zjZ3bsccz05b2es8dfPx_mv-vbu-ub-Y_b2klltjWhVEiqVVK1Q8dFawQnadALrdEtOm78AK0H6TgCCOd7I_q-xUH3Ti-8k-fs-yF3k-LzjvLWrkPen4MTxV22RiijdWtkIcWBdCnmnMjbTQprTK-Wg90btCu7N2j3Bi1wWwyWoYv3-N1iTcP_kX_KCvDtAHiMFpcpZPt4XxK6YleqsrsQVweCioaXQMlmF6h4HEIit7VDDB9d8AZPJIo2</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>927988493</pqid></control><display><type>article</type><title>Clinical and biological significance of Cdk10 in hepatocellular carcinoma</title><source>ScienceDirect Freedom Collection</source><creator>Zhong, Xiang-yu ; Xu, Xiao-xue ; Yu, Jian-hua ; Jiang, Gui-xing ; Yu, Yang ; Tai, Sheng ; Wang, Zhi-dong ; Cui, Yun-fu</creator><creatorcontrib>Zhong, Xiang-yu ; Xu, Xiao-xue ; Yu, Jian-hua ; Jiang, Gui-xing ; Yu, Yang ; Tai, Sheng ; Wang, Zhi-dong ; Cui, Yun-fu</creatorcontrib><description>Cyclin-dependent kinase 10 (Cdk10) is a Cdc2-related kinase and plays an essential role in the progression from the G2 to M phase of the cell cycle. However, relative little is known about its expression pattern, clinical relevance, and biological function in hepatocellular carcinoma (HCC). In the present study, we investigated the mRNA and protein expression levels of Cdk10 in 127 pairs of HCC samples and adjacent nontumorous liver tissues and evaluated its clinical significance. Additionally, we assessed the effects of restoration of Cdk10 on cell proliferation and drug sensitivity in HCC cells. We showed that the Cdk10 mRNA and protein expression was markedly decreased in HCC samples compared to adjacent nontumorous liver tissues. Quantitative real-time polymerase chain reaction and immunohistochemical studies revealed that reduced Cdk10 expression was significantly associated with alpha-fetoprotein levels, tumor size, and tumor stage. Ectopic expression of Cdk10 reduced HCC cell proliferation, blocked the cell cycle at the G0-G1 phase, as well as inhibited cell migration and anchorage-independent growth. Additionally, Cdk10 overexpression enhanced the chemosensitivity of HCC cells to cisplatin and epidoxorubicin, two chemotherapeutic agents commonly used in HCC. These data collectively demonstrate that reduced Cdk10 expression is closely linked to HCC development and progression. Restoration of its expression may have therapeutic benefits in treating this malignancy.
► HCC tissues show downregulation of Cdk10. ► Cdk10 reduction correlates with AFP levels, tumor size, and tumor stage in HCC. ► Cdk10 restoration inhibits HCC cell growth and migration. ► Cdk10 overexpression confers chemosensitivity to HCC cells.</description><identifier>ISSN: 0378-1119</identifier><identifier>EISSN: 1879-0038</identifier><identifier>DOI: 10.1016/j.gene.2012.01.022</identifier><identifier>PMID: 22326270</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Aged ; Base Sequence ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - enzymology ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - pathology ; Cdk10 ; Cell Cycle ; Cell Line, Tumor ; cell movement ; Cell Proliferation ; cisplatin ; Cisplatin - pharmacology ; clinical significance ; cyclin-dependent kinase ; Cyclin-Dependent Kinases - genetics ; Cyclin-Dependent Kinases - metabolism ; Down-Regulation ; drug resistance ; Drug Resistance, Neoplasm ; Epirubicin - analogs & derivatives ; Epirubicin - pharmacology ; Female ; Glucuronates - pharmacology ; HCC ; hepatoma ; Humans ; Immunohistochemistry ; liver ; Liver Neoplasms - drug therapy ; Liver Neoplasms - enzymology ; Liver Neoplasms - genetics ; Liver Neoplasms - pathology ; Male ; messenger RNA ; Middle Aged ; mitosis ; proliferation ; protein synthesis ; quantitative polymerase chain reaction ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; RNA, Neoplasm - genetics ; RNA, Neoplasm - metabolism</subject><ispartof>Gene, 2012-04, Vol.498 (1), p.68-74</ispartof><rights>2012 Elsevier B.V.</rights><rights>Copyright © 2012 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c379t-ea37ae747374d5124921e39af288acb519fd04f03c1a002cf692664ad86c8bfc3</citedby><cites>FETCH-LOGICAL-c379t-ea37ae747374d5124921e39af288acb519fd04f03c1a002cf692664ad86c8bfc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22326270$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhong, Xiang-yu</creatorcontrib><creatorcontrib>Xu, Xiao-xue</creatorcontrib><creatorcontrib>Yu, Jian-hua</creatorcontrib><creatorcontrib>Jiang, Gui-xing</creatorcontrib><creatorcontrib>Yu, Yang</creatorcontrib><creatorcontrib>Tai, Sheng</creatorcontrib><creatorcontrib>Wang, Zhi-dong</creatorcontrib><creatorcontrib>Cui, Yun-fu</creatorcontrib><title>Clinical and biological significance of Cdk10 in hepatocellular carcinoma</title><title>Gene</title><addtitle>Gene</addtitle><description>Cyclin-dependent kinase 10 (Cdk10) is a Cdc2-related kinase and plays an essential role in the progression from the G2 to M phase of the cell cycle. However, relative little is known about its expression pattern, clinical relevance, and biological function in hepatocellular carcinoma (HCC). In the present study, we investigated the mRNA and protein expression levels of Cdk10 in 127 pairs of HCC samples and adjacent nontumorous liver tissues and evaluated its clinical significance. Additionally, we assessed the effects of restoration of Cdk10 on cell proliferation and drug sensitivity in HCC cells. We showed that the Cdk10 mRNA and protein expression was markedly decreased in HCC samples compared to adjacent nontumorous liver tissues. Quantitative real-time polymerase chain reaction and immunohistochemical studies revealed that reduced Cdk10 expression was significantly associated with alpha-fetoprotein levels, tumor size, and tumor stage. Ectopic expression of Cdk10 reduced HCC cell proliferation, blocked the cell cycle at the G0-G1 phase, as well as inhibited cell migration and anchorage-independent growth. Additionally, Cdk10 overexpression enhanced the chemosensitivity of HCC cells to cisplatin and epidoxorubicin, two chemotherapeutic agents commonly used in HCC. These data collectively demonstrate that reduced Cdk10 expression is closely linked to HCC development and progression. Restoration of its expression may have therapeutic benefits in treating this malignancy.
► HCC tissues show downregulation of Cdk10. ► Cdk10 reduction correlates with AFP levels, tumor size, and tumor stage in HCC. ► Cdk10 restoration inhibits HCC cell growth and migration. ► Cdk10 overexpression confers chemosensitivity to HCC cells.</description><subject>Aged</subject><subject>Base Sequence</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Carcinoma, Hepatocellular - enzymology</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cdk10</subject><subject>Cell Cycle</subject><subject>Cell Line, Tumor</subject><subject>cell movement</subject><subject>Cell Proliferation</subject><subject>cisplatin</subject><subject>Cisplatin - pharmacology</subject><subject>clinical significance</subject><subject>cyclin-dependent kinase</subject><subject>Cyclin-Dependent Kinases - genetics</subject><subject>Cyclin-Dependent Kinases - metabolism</subject><subject>Down-Regulation</subject><subject>drug resistance</subject><subject>Drug Resistance, Neoplasm</subject><subject>Epirubicin - analogs & derivatives</subject><subject>Epirubicin - pharmacology</subject><subject>Female</subject><subject>Glucuronates - pharmacology</subject><subject>HCC</subject><subject>hepatoma</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>liver</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - enzymology</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - pathology</subject><subject>Male</subject><subject>messenger RNA</subject><subject>Middle Aged</subject><subject>mitosis</subject><subject>proliferation</subject><subject>protein synthesis</subject><subject>quantitative polymerase chain reaction</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA, Neoplasm - genetics</subject><subject>RNA, Neoplasm - metabolism</subject><issn>0378-1119</issn><issn>1879-0038</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNp9kMFOGzEQhi1UBIH2BXqge-tpl7G9u7YlLlXUUiQkDsDZmnjHqcNmHewEibfHaWiP-DIe6Zt_Rh9jXzk0HHh_uWqWNFEjgIsGeANCHLEZ18rUAFJ_YjOQStecc3PKznJeQXldJ07YqRBS9ELBjN3MxzAFh2OF01AtQhzj8m-bw3IKvnwnR1X01Xx44lCFqfpDG9xGR-O4GzFVDpMLU1zjZ3bsccz05b2es8dfPx_mv-vbu-ub-Y_b2klltjWhVEiqVVK1Q8dFawQnadALrdEtOm78AK0H6TgCCOd7I_q-xUH3Ti-8k-fs-yF3k-LzjvLWrkPen4MTxV22RiijdWtkIcWBdCnmnMjbTQprTK-Wg90btCu7N2j3Bi1wWwyWoYv3-N1iTcP_kX_KCvDtAHiMFpcpZPt4XxK6YleqsrsQVweCioaXQMlmF6h4HEIit7VDDB9d8AZPJIo2</recordid><startdate>20120425</startdate><enddate>20120425</enddate><creator>Zhong, Xiang-yu</creator><creator>Xu, Xiao-xue</creator><creator>Yu, Jian-hua</creator><creator>Jiang, Gui-xing</creator><creator>Yu, Yang</creator><creator>Tai, Sheng</creator><creator>Wang, Zhi-dong</creator><creator>Cui, Yun-fu</creator><general>Elsevier B.V</general><scope>FBQ</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>20120425</creationdate><title>Clinical and biological significance of Cdk10 in hepatocellular carcinoma</title><author>Zhong, Xiang-yu ; Xu, Xiao-xue ; Yu, Jian-hua ; Jiang, Gui-xing ; Yu, Yang ; Tai, Sheng ; Wang, Zhi-dong ; Cui, Yun-fu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c379t-ea37ae747374d5124921e39af288acb519fd04f03c1a002cf692664ad86c8bfc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aged</topic><topic>Base Sequence</topic><topic>Carcinoma, Hepatocellular - drug therapy</topic><topic>Carcinoma, Hepatocellular - enzymology</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cdk10</topic><topic>Cell Cycle</topic><topic>Cell Line, Tumor</topic><topic>cell movement</topic><topic>Cell Proliferation</topic><topic>cisplatin</topic><topic>Cisplatin - pharmacology</topic><topic>clinical significance</topic><topic>cyclin-dependent kinase</topic><topic>Cyclin-Dependent Kinases - genetics</topic><topic>Cyclin-Dependent Kinases - metabolism</topic><topic>Down-Regulation</topic><topic>drug resistance</topic><topic>Drug Resistance, Neoplasm</topic><topic>Epirubicin - analogs & derivatives</topic><topic>Epirubicin - pharmacology</topic><topic>Female</topic><topic>Glucuronates - pharmacology</topic><topic>HCC</topic><topic>hepatoma</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>liver</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - enzymology</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - pathology</topic><topic>Male</topic><topic>messenger RNA</topic><topic>Middle Aged</topic><topic>mitosis</topic><topic>proliferation</topic><topic>protein synthesis</topic><topic>quantitative polymerase chain reaction</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA, Neoplasm - genetics</topic><topic>RNA, Neoplasm - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhong, Xiang-yu</creatorcontrib><creatorcontrib>Xu, Xiao-xue</creatorcontrib><creatorcontrib>Yu, Jian-hua</creatorcontrib><creatorcontrib>Jiang, Gui-xing</creatorcontrib><creatorcontrib>Yu, Yang</creatorcontrib><creatorcontrib>Tai, Sheng</creatorcontrib><creatorcontrib>Wang, Zhi-dong</creatorcontrib><creatorcontrib>Cui, Yun-fu</creatorcontrib><collection>AGRIS</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>Gene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhong, Xiang-yu</au><au>Xu, Xiao-xue</au><au>Yu, Jian-hua</au><au>Jiang, Gui-xing</au><au>Yu, Yang</au><au>Tai, Sheng</au><au>Wang, Zhi-dong</au><au>Cui, Yun-fu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical and biological significance of Cdk10 in hepatocellular carcinoma</atitle><jtitle>Gene</jtitle><addtitle>Gene</addtitle><date>2012-04-25</date><risdate>2012</risdate><volume>498</volume><issue>1</issue><spage>68</spage><epage>74</epage><pages>68-74</pages><issn>0378-1119</issn><eissn>1879-0038</eissn><notes>http://dx.doi.org/10.1016/j.gene.2012.01.022</notes><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Cyclin-dependent kinase 10 (Cdk10) is a Cdc2-related kinase and plays an essential role in the progression from the G2 to M phase of the cell cycle. However, relative little is known about its expression pattern, clinical relevance, and biological function in hepatocellular carcinoma (HCC). In the present study, we investigated the mRNA and protein expression levels of Cdk10 in 127 pairs of HCC samples and adjacent nontumorous liver tissues and evaluated its clinical significance. Additionally, we assessed the effects of restoration of Cdk10 on cell proliferation and drug sensitivity in HCC cells. We showed that the Cdk10 mRNA and protein expression was markedly decreased in HCC samples compared to adjacent nontumorous liver tissues. Quantitative real-time polymerase chain reaction and immunohistochemical studies revealed that reduced Cdk10 expression was significantly associated with alpha-fetoprotein levels, tumor size, and tumor stage. Ectopic expression of Cdk10 reduced HCC cell proliferation, blocked the cell cycle at the G0-G1 phase, as well as inhibited cell migration and anchorage-independent growth. Additionally, Cdk10 overexpression enhanced the chemosensitivity of HCC cells to cisplatin and epidoxorubicin, two chemotherapeutic agents commonly used in HCC. These data collectively demonstrate that reduced Cdk10 expression is closely linked to HCC development and progression. Restoration of its expression may have therapeutic benefits in treating this malignancy.
► HCC tissues show downregulation of Cdk10. ► Cdk10 reduction correlates with AFP levels, tumor size, and tumor stage in HCC. ► Cdk10 restoration inhibits HCC cell growth and migration. ► Cdk10 overexpression confers chemosensitivity to HCC cells.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>22326270</pmid><doi>10.1016/j.gene.2012.01.022</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0378-1119 |
| ispartof | Gene, 2012-04, Vol.498 (1), p.68-74 |
| issn | 0378-1119 1879-0038 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_927988493 |
| source | ScienceDirect Freedom Collection |
| subjects | Aged Base Sequence Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - enzymology Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - pathology Cdk10 Cell Cycle Cell Line, Tumor cell movement Cell Proliferation cisplatin Cisplatin - pharmacology clinical significance cyclin-dependent kinase Cyclin-Dependent Kinases - genetics Cyclin-Dependent Kinases - metabolism Down-Regulation drug resistance Drug Resistance, Neoplasm Epirubicin - analogs & derivatives Epirubicin - pharmacology Female Glucuronates - pharmacology HCC hepatoma Humans Immunohistochemistry liver Liver Neoplasms - drug therapy Liver Neoplasms - enzymology Liver Neoplasms - genetics Liver Neoplasms - pathology Male messenger RNA Middle Aged mitosis proliferation protein synthesis quantitative polymerase chain reaction RNA, Messenger - genetics RNA, Messenger - metabolism RNA, Neoplasm - genetics RNA, Neoplasm - metabolism |
| title | Clinical and biological significance of Cdk10 in hepatocellular carcinoma |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-22T04%3A44%3A53IST&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=Clinical%20and%20biological%20significance%20of%20Cdk10%20in%20hepatocellular%20carcinoma&rft.jtitle=Gene&rft.au=Zhong,%20Xiang-yu&rft.date=2012-04-25&rft.volume=498&rft.issue=1&rft.spage=68&rft.epage=74&rft.pages=68-74&rft.issn=0378-1119&rft.eissn=1879-0038&rft_id=info:doi/10.1016/j.gene.2012.01.022&rft_dat=%3Cproquest_cross%3E927988493%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c379t-ea37ae747374d5124921e39af288acb519fd04f03c1a002cf692664ad86c8bfc3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=927988493&rft_id=info:pmid/22326270&rfr_iscdi=true |