PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer
PHA-739358 is a small-molecule 3-aminopyrazole derivative with strong activity against Aurora kinases and cross-reactivities with some receptor tyrosine kinases relevant for cancer. PHA-739358 inhibits all Aurora kinase family members and shows a dominant Aurora B kinase inhibition–related cellular...
Gespeichert in:
| Veröffentlicht in: | Molecular cancer therapeutics 2007-12, Vol.6 (12), p.3158-3168 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 3168 |
|---|---|
| container_issue | 12 |
| container_start_page | 3158 |
| container_title | Molecular cancer therapeutics |
| container_volume | 6 |
| creator | Carpinelli, Patrizia Ceruti, Roberta Giorgini, Maria Laura Cappella, Paolo Gianellini, Laura Croci, Valter Degrassi, Anna Texido, Gemma Rocchetti, Maurizio Vianello, Paola Rusconi, Luisa Storici, Paola Zugnoni, Paola Arrigoni, Claudio Soncini, Chiara Alli, Cristina Patton, Veronica Marsiglio, Aurelio Ballinari, Dario Pesenti, Enrico Fancelli, Daniele Moll, Jürgen |
| description | PHA-739358 is a small-molecule 3-aminopyrazole derivative with strong activity against Aurora kinases and cross-reactivities
with some receptor tyrosine kinases relevant for cancer. PHA-739358 inhibits all Aurora kinase family members and shows a
dominant Aurora B kinase inhibition–related cellular phenotype and mechanism of action in cells in vitro and in vivo. p53 status–dependent endoreduplication is observed upon treatment of cells with PHA-739358, and phosphorylation of histone
H3 in Ser 10 is inhibited. The compound has significant antitumor activity in different xenografts and spontaneous and transgenic animal
tumor models and shows a favorable pharmacokinetic and safety profile. In vivo target modulation is observed as assessed by the inhibition of the phosphorylation of histone H3, which has been validated
preclinically as a candidate biomarker for the clinical phase. Pharmacokinetics/pharmacodynamics modeling was used to define
drug potency and to support the prediction of active clinical doses and schedules. We conclude that PHA-739358, which is currently
tested in clinical trials, has great therapeutic potential in anticancer therapy in a wide range of cancers. [Mol Cancer Ther
2007;6(12):3158–68] |
| doi_str_mv | 10.1158/1535-7163.MCT-07-0444 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_69074300</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20469743</sourcerecordid><originalsourceid>FETCH-LOGICAL-c418t-2c09f072bff4d4c481e34e25d635e26a40324ada772bf89ce57fdcb69fe4a2f53</originalsourceid><addsrcrecordid>eNqFkU1v1DAQhi1URD_gJ1D5VHFoij9j57haAa1UBIdytrzOuDFk463tbcW_x2lW7ZHTjEbPOzN6X4Q-UnJFqdSfqeSyUbTlV9_Xdw1RDRFCvEEnda4bLak4eu4X5hid5vybEKo7Rt-hY6qJ7hQlJ2j6eb1qFO-41JfY4l0sMBUcpiFsQokJR49X-xSTxX_CZDNk_BTKUMkMI7gSHgEXm-7hRRPihHcp-jACTpV5tHVfidjZyUF6j956O2b4cKhn6NfXL3fr6-b2x7eb9eq2cYLq0jBHOk8U23gveuGEpsAFMNm3XAJrrSCcCdtbNSO6cyCV792m7TwIy7zkZ-hi2VtfedhDLmYbsoNxtBPEfTZtR5TghPwXZES0XUUrKBfQpZhzAm92KWxt-msoMXMiZnbbzG6bmoghysyJVN354cB-s4X-VXWIoAKfFmAI98NTSGAWqxJksMkNpjWUGV4v8H-4TJU0</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20469743</pqid></control><display><type>article</type><title>PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Carpinelli, Patrizia ; Ceruti, Roberta ; Giorgini, Maria Laura ; Cappella, Paolo ; Gianellini, Laura ; Croci, Valter ; Degrassi, Anna ; Texido, Gemma ; Rocchetti, Maurizio ; Vianello, Paola ; Rusconi, Luisa ; Storici, Paola ; Zugnoni, Paola ; Arrigoni, Claudio ; Soncini, Chiara ; Alli, Cristina ; Patton, Veronica ; Marsiglio, Aurelio ; Ballinari, Dario ; Pesenti, Enrico ; Fancelli, Daniele ; Moll, Jürgen</creator><creatorcontrib>Carpinelli, Patrizia ; Ceruti, Roberta ; Giorgini, Maria Laura ; Cappella, Paolo ; Gianellini, Laura ; Croci, Valter ; Degrassi, Anna ; Texido, Gemma ; Rocchetti, Maurizio ; Vianello, Paola ; Rusconi, Luisa ; Storici, Paola ; Zugnoni, Paola ; Arrigoni, Claudio ; Soncini, Chiara ; Alli, Cristina ; Patton, Veronica ; Marsiglio, Aurelio ; Ballinari, Dario ; Pesenti, Enrico ; Fancelli, Daniele ; Moll, Jürgen</creatorcontrib><description>PHA-739358 is a small-molecule 3-aminopyrazole derivative with strong activity against Aurora kinases and cross-reactivities
with some receptor tyrosine kinases relevant for cancer. PHA-739358 inhibits all Aurora kinase family members and shows a
dominant Aurora B kinase inhibition–related cellular phenotype and mechanism of action in cells in vitro and in vivo. p53 status–dependent endoreduplication is observed upon treatment of cells with PHA-739358, and phosphorylation of histone
H3 in Ser 10 is inhibited. The compound has significant antitumor activity in different xenografts and spontaneous and transgenic animal
tumor models and shows a favorable pharmacokinetic and safety profile. In vivo target modulation is observed as assessed by the inhibition of the phosphorylation of histone H3, which has been validated
preclinically as a candidate biomarker for the clinical phase. Pharmacokinetics/pharmacodynamics modeling was used to define
drug potency and to support the prediction of active clinical doses and schedules. We conclude that PHA-739358, which is currently
tested in clinical trials, has great therapeutic potential in anticancer therapy in a wide range of cancers. [Mol Cancer Ther
2007;6(12):3158–68]</description><identifier>ISSN: 1535-7163</identifier><identifier>EISSN: 1538-8514</identifier><identifier>DOI: 10.1158/1535-7163.MCT-07-0444</identifier><identifier>PMID: 18089710</identifier><language>eng</language><publisher>United States: American Association for Cancer Research</publisher><subject>Abl ; Animals ; Aurora kinase ; Aurora Kinase B ; Aurora Kinases ; Benzamides - pharmacokinetics ; Benzamides - pharmacology ; Benzamides - therapeutic use ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Female ; Humans ; Immunohistochemistry ; Male ; Mice ; Mice, Nude ; Neoplasms - drug therapy ; Neoplasms - enzymology ; Phosphorylation ; Protein-Serine-Threonine Kinases - antagonists & inhibitors ; Pyrazoles - pharmacokinetics ; Pyrazoles - pharmacology ; Pyrazoles - therapeutic use ; Rats ; Rats, Sprague-Dawley ; Ret ; small molecule kinase inhibitor ; TrkA</subject><ispartof>Molecular cancer therapeutics, 2007-12, Vol.6 (12), p.3158-3168</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c418t-2c09f072bff4d4c481e34e25d635e26a40324ada772bf89ce57fdcb69fe4a2f53</citedby><cites>FETCH-LOGICAL-c418t-2c09f072bff4d4c481e34e25d635e26a40324ada772bf89ce57fdcb69fe4a2f53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3343,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18089710$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carpinelli, Patrizia</creatorcontrib><creatorcontrib>Ceruti, Roberta</creatorcontrib><creatorcontrib>Giorgini, Maria Laura</creatorcontrib><creatorcontrib>Cappella, Paolo</creatorcontrib><creatorcontrib>Gianellini, Laura</creatorcontrib><creatorcontrib>Croci, Valter</creatorcontrib><creatorcontrib>Degrassi, Anna</creatorcontrib><creatorcontrib>Texido, Gemma</creatorcontrib><creatorcontrib>Rocchetti, Maurizio</creatorcontrib><creatorcontrib>Vianello, Paola</creatorcontrib><creatorcontrib>Rusconi, Luisa</creatorcontrib><creatorcontrib>Storici, Paola</creatorcontrib><creatorcontrib>Zugnoni, Paola</creatorcontrib><creatorcontrib>Arrigoni, Claudio</creatorcontrib><creatorcontrib>Soncini, Chiara</creatorcontrib><creatorcontrib>Alli, Cristina</creatorcontrib><creatorcontrib>Patton, Veronica</creatorcontrib><creatorcontrib>Marsiglio, Aurelio</creatorcontrib><creatorcontrib>Ballinari, Dario</creatorcontrib><creatorcontrib>Pesenti, Enrico</creatorcontrib><creatorcontrib>Fancelli, Daniele</creatorcontrib><creatorcontrib>Moll, Jürgen</creatorcontrib><title>PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer</title><title>Molecular cancer therapeutics</title><addtitle>Mol Cancer Ther</addtitle><description>PHA-739358 is a small-molecule 3-aminopyrazole derivative with strong activity against Aurora kinases and cross-reactivities
with some receptor tyrosine kinases relevant for cancer. PHA-739358 inhibits all Aurora kinase family members and shows a
dominant Aurora B kinase inhibition–related cellular phenotype and mechanism of action in cells in vitro and in vivo. p53 status–dependent endoreduplication is observed upon treatment of cells with PHA-739358, and phosphorylation of histone
H3 in Ser 10 is inhibited. The compound has significant antitumor activity in different xenografts and spontaneous and transgenic animal
tumor models and shows a favorable pharmacokinetic and safety profile. In vivo target modulation is observed as assessed by the inhibition of the phosphorylation of histone H3, which has been validated
preclinically as a candidate biomarker for the clinical phase. Pharmacokinetics/pharmacodynamics modeling was used to define
drug potency and to support the prediction of active clinical doses and schedules. We conclude that PHA-739358, which is currently
tested in clinical trials, has great therapeutic potential in anticancer therapy in a wide range of cancers. [Mol Cancer Ther
2007;6(12):3158–68]</description><subject>Abl</subject><subject>Animals</subject><subject>Aurora kinase</subject><subject>Aurora Kinase B</subject><subject>Aurora Kinases</subject><subject>Benzamides - pharmacokinetics</subject><subject>Benzamides - pharmacology</subject><subject>Benzamides - therapeutic use</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Female</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - enzymology</subject><subject>Phosphorylation</subject><subject>Protein-Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Pyrazoles - pharmacokinetics</subject><subject>Pyrazoles - pharmacology</subject><subject>Pyrazoles - therapeutic use</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Ret</subject><subject>small molecule kinase inhibitor</subject><subject>TrkA</subject><issn>1535-7163</issn><issn>1538-8514</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi1URD_gJ1D5VHFoij9j57haAa1UBIdytrzOuDFk463tbcW_x2lW7ZHTjEbPOzN6X4Q-UnJFqdSfqeSyUbTlV9_Xdw1RDRFCvEEnda4bLak4eu4X5hid5vybEKo7Rt-hY6qJ7hQlJ2j6eb1qFO-41JfY4l0sMBUcpiFsQokJR49X-xSTxX_CZDNk_BTKUMkMI7gSHgEXm-7hRRPihHcp-jACTpV5tHVfidjZyUF6j956O2b4cKhn6NfXL3fr6-b2x7eb9eq2cYLq0jBHOk8U23gveuGEpsAFMNm3XAJrrSCcCdtbNSO6cyCV792m7TwIy7zkZ-hi2VtfedhDLmYbsoNxtBPEfTZtR5TghPwXZES0XUUrKBfQpZhzAm92KWxt-msoMXMiZnbbzG6bmoghysyJVN354cB-s4X-VXWIoAKfFmAI98NTSGAWqxJksMkNpjWUGV4v8H-4TJU0</recordid><startdate>20071201</startdate><enddate>20071201</enddate><creator>Carpinelli, Patrizia</creator><creator>Ceruti, Roberta</creator><creator>Giorgini, Maria Laura</creator><creator>Cappella, Paolo</creator><creator>Gianellini, Laura</creator><creator>Croci, Valter</creator><creator>Degrassi, Anna</creator><creator>Texido, Gemma</creator><creator>Rocchetti, Maurizio</creator><creator>Vianello, Paola</creator><creator>Rusconi, Luisa</creator><creator>Storici, Paola</creator><creator>Zugnoni, Paola</creator><creator>Arrigoni, Claudio</creator><creator>Soncini, Chiara</creator><creator>Alli, Cristina</creator><creator>Patton, Veronica</creator><creator>Marsiglio, Aurelio</creator><creator>Ballinari, Dario</creator><creator>Pesenti, Enrico</creator><creator>Fancelli, Daniele</creator><creator>Moll, Jürgen</creator><general>American Association for Cancer Research</general><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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20071201</creationdate><title>PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer</title><author>Carpinelli, Patrizia ; Ceruti, Roberta ; Giorgini, Maria Laura ; Cappella, Paolo ; Gianellini, Laura ; Croci, Valter ; Degrassi, Anna ; Texido, Gemma ; Rocchetti, Maurizio ; Vianello, Paola ; Rusconi, Luisa ; Storici, Paola ; Zugnoni, Paola ; Arrigoni, Claudio ; Soncini, Chiara ; Alli, Cristina ; Patton, Veronica ; Marsiglio, Aurelio ; Ballinari, Dario ; Pesenti, Enrico ; Fancelli, Daniele ; Moll, Jürgen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-2c09f072bff4d4c481e34e25d635e26a40324ada772bf89ce57fdcb69fe4a2f53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Abl</topic><topic>Animals</topic><topic>Aurora kinase</topic><topic>Aurora Kinase B</topic><topic>Aurora Kinases</topic><topic>Benzamides - pharmacokinetics</topic><topic>Benzamides - pharmacology</topic><topic>Benzamides - therapeutic use</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Female</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - enzymology</topic><topic>Phosphorylation</topic><topic>Protein-Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>Pyrazoles - pharmacokinetics</topic><topic>Pyrazoles - pharmacology</topic><topic>Pyrazoles - therapeutic use</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Ret</topic><topic>small molecule kinase inhibitor</topic><topic>TrkA</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carpinelli, Patrizia</creatorcontrib><creatorcontrib>Ceruti, Roberta</creatorcontrib><creatorcontrib>Giorgini, Maria Laura</creatorcontrib><creatorcontrib>Cappella, Paolo</creatorcontrib><creatorcontrib>Gianellini, Laura</creatorcontrib><creatorcontrib>Croci, Valter</creatorcontrib><creatorcontrib>Degrassi, Anna</creatorcontrib><creatorcontrib>Texido, Gemma</creatorcontrib><creatorcontrib>Rocchetti, Maurizio</creatorcontrib><creatorcontrib>Vianello, Paola</creatorcontrib><creatorcontrib>Rusconi, Luisa</creatorcontrib><creatorcontrib>Storici, Paola</creatorcontrib><creatorcontrib>Zugnoni, Paola</creatorcontrib><creatorcontrib>Arrigoni, Claudio</creatorcontrib><creatorcontrib>Soncini, Chiara</creatorcontrib><creatorcontrib>Alli, Cristina</creatorcontrib><creatorcontrib>Patton, Veronica</creatorcontrib><creatorcontrib>Marsiglio, Aurelio</creatorcontrib><creatorcontrib>Ballinari, Dario</creatorcontrib><creatorcontrib>Pesenti, Enrico</creatorcontrib><creatorcontrib>Fancelli, Daniele</creatorcontrib><creatorcontrib>Moll, Jürgen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular cancer therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carpinelli, Patrizia</au><au>Ceruti, Roberta</au><au>Giorgini, Maria Laura</au><au>Cappella, Paolo</au><au>Gianellini, Laura</au><au>Croci, Valter</au><au>Degrassi, Anna</au><au>Texido, Gemma</au><au>Rocchetti, Maurizio</au><au>Vianello, Paola</au><au>Rusconi, Luisa</au><au>Storici, Paola</au><au>Zugnoni, Paola</au><au>Arrigoni, Claudio</au><au>Soncini, Chiara</au><au>Alli, Cristina</au><au>Patton, Veronica</au><au>Marsiglio, Aurelio</au><au>Ballinari, Dario</au><au>Pesenti, Enrico</au><au>Fancelli, Daniele</au><au>Moll, Jürgen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer</atitle><jtitle>Molecular cancer therapeutics</jtitle><addtitle>Mol Cancer Ther</addtitle><date>2007-12-01</date><risdate>2007</risdate><volume>6</volume><issue>12</issue><spage>3158</spage><epage>3168</epage><pages>3158-3168</pages><issn>1535-7163</issn><eissn>1538-8514</eissn><abstract>PHA-739358 is a small-molecule 3-aminopyrazole derivative with strong activity against Aurora kinases and cross-reactivities
with some receptor tyrosine kinases relevant for cancer. PHA-739358 inhibits all Aurora kinase family members and shows a
dominant Aurora B kinase inhibition–related cellular phenotype and mechanism of action in cells in vitro and in vivo. p53 status–dependent endoreduplication is observed upon treatment of cells with PHA-739358, and phosphorylation of histone
H3 in Ser 10 is inhibited. The compound has significant antitumor activity in different xenografts and spontaneous and transgenic animal
tumor models and shows a favorable pharmacokinetic and safety profile. In vivo target modulation is observed as assessed by the inhibition of the phosphorylation of histone H3, which has been validated
preclinically as a candidate biomarker for the clinical phase. Pharmacokinetics/pharmacodynamics modeling was used to define
drug potency and to support the prediction of active clinical doses and schedules. We conclude that PHA-739358, which is currently
tested in clinical trials, has great therapeutic potential in anticancer therapy in a wide range of cancers. [Mol Cancer Ther
2007;6(12):3158–68]</abstract><cop>United States</cop><pub>American Association for Cancer Research</pub><pmid>18089710</pmid><doi>10.1158/1535-7163.MCT-07-0444</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1535-7163 |
| ispartof | Molecular cancer therapeutics, 2007-12, Vol.6 (12), p.3158-3168 |
| issn | 1535-7163 1538-8514 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_69074300 |
| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Abl Animals Aurora kinase Aurora Kinase B Aurora Kinases Benzamides - pharmacokinetics Benzamides - pharmacology Benzamides - therapeutic use Cell Line, Tumor Cell Proliferation - drug effects Female Humans Immunohistochemistry Male Mice Mice, Nude Neoplasms - drug therapy Neoplasms - enzymology Phosphorylation Protein-Serine-Threonine Kinases - antagonists & inhibitors Pyrazoles - pharmacokinetics Pyrazoles - pharmacology Pyrazoles - therapeutic use Rats Rats, Sprague-Dawley Ret small molecule kinase inhibitor TrkA |
| title | PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T02%3A48%3A29IST&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=PHA-739358,%20a%20potent%20inhibitor%20of%20Aurora%20kinases%20with%20a%20selective%20target%20inhibition%20profile%20relevant%20to%20cancer&rft.jtitle=Molecular%20cancer%20therapeutics&rft.au=Carpinelli,%20Patrizia&rft.date=2007-12-01&rft.volume=6&rft.issue=12&rft.spage=3158&rft.epage=3168&rft.pages=3158-3168&rft.issn=1535-7163&rft.eissn=1538-8514&rft_id=info:doi/10.1158/1535-7163.MCT-07-0444&rft_dat=%3Cproquest_cross%3E20469743%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=20469743&rft_id=info:pmid/18089710&rfr_iscdi=true |