Immunization with liposome-anchored pegylated peptides modulates doxorubicin sensitivity in P-glycoprotein-expressing P388 cells
Abstract The clinical use of chemotherapy in cancer treatment is limited by the occurrence of multidrug resistance (MDR) associated with the overexpression of membrane transporters, one of the best known is P-glycoprotein (Pgp), that actively expels drugs out of tumor cells. To overcome Pgp-mediated...
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| Veröffentlicht in: | Cancer letters 2007-11, Vol.257 (2), p.165-171 |
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| creator | Gatouillat, Grégory Odot, Johann Balasse, Emilie Nicolau, Claude Tosi, Pierre-François Hickman, David T López-Deber, María Pilar Madoulet, Claudie |
| description | Abstract The clinical use of chemotherapy in cancer treatment is limited by the occurrence of multidrug resistance (MDR) associated with the overexpression of membrane transporters, one of the best known is P-glycoprotein (Pgp), that actively expels drugs out of tumor cells. To overcome Pgp-mediated MDR, synthetic peptides corresponding to fragments from extracellular loops 1, 2 and 4 of the murine Pgp were coupled to polyethylene glycol–distearoylphosphatidylethanolamine and inserted into empty or monophosphoryl lipid A-containing liposomes. This formulation elicited specific antibodies which blocked Pgp-mediated efflux of doxorubicin, resulting in increased intracellular drug accumulation and subsequent potentiation of the cytotoxic effect of doxorubicin on multidrug-resistant P388 (P388R) cells. Previous immunizations with MDR1 peptides improved the efficiency of chemotherapy against P388R cells in vivo , with an increase of 83% of mice survival time. Overall, these results suggest that this approach can modulate Pgp activity by blocking drug efflux and may have clinical relevance as an alternative strategy to toxic chemosensitizers in drug-resistant cancer therapy. |
| doi_str_mv | 10.1016/j.canlet.2007.04.001 |
| format | Article |
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To overcome Pgp-mediated MDR, synthetic peptides corresponding to fragments from extracellular loops 1, 2 and 4 of the murine Pgp were coupled to polyethylene glycol–distearoylphosphatidylethanolamine and inserted into empty or monophosphoryl lipid A-containing liposomes. This formulation elicited specific antibodies which blocked Pgp-mediated efflux of doxorubicin, resulting in increased intracellular drug accumulation and subsequent potentiation of the cytotoxic effect of doxorubicin on multidrug-resistant P388 (P388R) cells. Previous immunizations with MDR1 peptides improved the efficiency of chemotherapy against P388R cells in vivo , with an increase of 83% of mice survival time. Overall, these results suggest that this approach can modulate Pgp activity by blocking drug efflux and may have clinical relevance as an alternative strategy to toxic chemosensitizers in drug-resistant cancer therapy.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2007.04.001</identifier><identifier>PMID: 17517470</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Amino Acid Sequence ; Animals ; Antibiotics, Antineoplastic - metabolism ; Antibiotics, Antineoplastic - pharmacokinetics ; Antibiotics, Antineoplastic - pharmacology ; Antibodies - administration & dosage ; Antibodies - immunology ; Antibodies - pharmacology ; ATP-Binding Cassette, Sub-Family B, Member 1 - chemistry ; ATP-Binding Cassette, Sub-Family B, Member 1 - immunology ; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism ; Blotting, Western ; Cancer ; Cell Line, Tumor ; Cell Survival - drug effects ; Cholesterol ; Dilution ; Dimensional analysis ; Doxorubicin - metabolism ; Doxorubicin - pharmacokinetics ; Doxorubicin - pharmacology ; Drug Resistance, Bacterial ; Female ; Flow Cytometry ; Hematology, Oncology and Palliative Medicine ; Hypotheses ; Immunization ; Immunization - methods ; Liposomes ; Liposomes - chemistry ; Mice ; Mice, Inbred Strains ; Molecular Sequence Data ; Molecular weight ; Multidrug resistance ; Neoplasms, Experimental - immunology ; Neoplasms, Experimental - pathology ; Neoplasms, Experimental - prevention & control ; P-Glycoprotein ; Pegylated peptides ; Peptides ; Peptides - chemistry ; Peptides - immunology ; Polyethylene Glycols - chemistry ; Proteins ; Studies ; Survival Analysis ; Tumors ; Vaccines, Subunit - administration & dosage ; Vaccines, Subunit - chemistry ; Vaccines, Subunit - immunology</subject><ispartof>Cancer letters, 2007-11, Vol.257 (2), p.165-171</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2007 Elsevier Ireland Ltd</rights><rights>Copyright Elsevier Limited Nov 18, 2007</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-6e32e9efef1dc3b565a04811613e054bde787efd0012f2e5b8be23c4ff8667ff3</citedby><cites>FETCH-LOGICAL-c443t-6e32e9efef1dc3b565a04811613e054bde787efd0012f2e5b8be23c4ff8667ff3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.canlet.2007.04.001$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17517470$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gatouillat, Grégory</creatorcontrib><creatorcontrib>Odot, Johann</creatorcontrib><creatorcontrib>Balasse, Emilie</creatorcontrib><creatorcontrib>Nicolau, Claude</creatorcontrib><creatorcontrib>Tosi, Pierre-François</creatorcontrib><creatorcontrib>Hickman, David T</creatorcontrib><creatorcontrib>López-Deber, María Pilar</creatorcontrib><creatorcontrib>Madoulet, Claudie</creatorcontrib><title>Immunization with liposome-anchored pegylated peptides modulates doxorubicin sensitivity in P-glycoprotein-expressing P388 cells</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><description>Abstract The clinical use of chemotherapy in cancer treatment is limited by the occurrence of multidrug resistance (MDR) associated with the overexpression of membrane transporters, one of the best known is P-glycoprotein (Pgp), that actively expels drugs out of tumor cells. To overcome Pgp-mediated MDR, synthetic peptides corresponding to fragments from extracellular loops 1, 2 and 4 of the murine Pgp were coupled to polyethylene glycol–distearoylphosphatidylethanolamine and inserted into empty or monophosphoryl lipid A-containing liposomes. This formulation elicited specific antibodies which blocked Pgp-mediated efflux of doxorubicin, resulting in increased intracellular drug accumulation and subsequent potentiation of the cytotoxic effect of doxorubicin on multidrug-resistant P388 (P388R) cells. Previous immunizations with MDR1 peptides improved the efficiency of chemotherapy against P388R cells in vivo , with an increase of 83% of mice survival time. Overall, these results suggest that this approach can modulate Pgp activity by blocking drug efflux and may have clinical relevance as an alternative strategy to toxic chemosensitizers in drug-resistant cancer therapy.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibiotics, Antineoplastic - metabolism</subject><subject>Antibiotics, Antineoplastic - pharmacokinetics</subject><subject>Antibiotics, Antineoplastic - pharmacology</subject><subject>Antibodies - administration & dosage</subject><subject>Antibodies - immunology</subject><subject>Antibodies - pharmacology</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - chemistry</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - immunology</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism</subject><subject>Blotting, Western</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Cholesterol</subject><subject>Dilution</subject><subject>Dimensional analysis</subject><subject>Doxorubicin - metabolism</subject><subject>Doxorubicin - pharmacokinetics</subject><subject>Doxorubicin - pharmacology</subject><subject>Drug Resistance, Bacterial</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Hypotheses</subject><subject>Immunization</subject><subject>Immunization - methods</subject><subject>Liposomes</subject><subject>Liposomes - chemistry</subject><subject>Mice</subject><subject>Mice, Inbred Strains</subject><subject>Molecular Sequence Data</subject><subject>Molecular weight</subject><subject>Multidrug resistance</subject><subject>Neoplasms, Experimental - immunology</subject><subject>Neoplasms, Experimental - pathology</subject><subject>Neoplasms, Experimental - prevention & control</subject><subject>P-Glycoprotein</subject><subject>Pegylated peptides</subject><subject>Peptides</subject><subject>Peptides - chemistry</subject><subject>Peptides - immunology</subject><subject>Polyethylene Glycols - chemistry</subject><subject>Proteins</subject><subject>Studies</subject><subject>Survival Analysis</subject><subject>Tumors</subject><subject>Vaccines, Subunit - administration & dosage</subject><subject>Vaccines, Subunit - chemistry</subject><subject>Vaccines, Subunit - immunology</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUV1r1TAYDqK4s-k_ECl43Zo0SdNzI8hwczBw4HYd2uTNWY5tUpN0rl750013Dgy88SofPB_v87wIvSO4Ipg0H_eV6twAqaoxFhVmFcbkBdqQVtSl2Lb4JdpgillJW8pP0GmMe4wxZ4K_RidEcCKYwBv052ocZ2d_d8l6V_yy6b4Y7OSjH6HsnLr3AXQxwW4ZuvR0m5LVEIvR63n9ioX2jz7MvVXWFRFctMk-2LQU-XlT7oZF-Sn4BNaV8DgFiNG6XXFD27ZQMAzxDXpluiHC2-N5hu4uvtyefy2vv11enX--LhVjNJUN0Bq2YMAQrWjPG95h1hLSEAo5Va9BtAKMziXUpgbetz3UVDFj2qYRxtAz9OGgm6f5OUNMcu_n4LKlJHzthdWcZRQ7oFTwMQYwcgp27MIiCZZr7XIvD7XLtXaJmcyOmfb-KD73I-hn0rHnDPh0AECO-GAhyKgsOAXaBlBJam__5_CvgBqss6obfsAC8TmLjLXE8vu6-nXzWGS24Fv6F7Rprbg</recordid><startdate>20071118</startdate><enddate>20071118</enddate><creator>Gatouillat, Grégory</creator><creator>Odot, Johann</creator><creator>Balasse, Emilie</creator><creator>Nicolau, Claude</creator><creator>Tosi, Pierre-François</creator><creator>Hickman, David T</creator><creator>López-Deber, María Pilar</creator><creator>Madoulet, Claudie</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Limited</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>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope></search><sort><creationdate>20071118</creationdate><title>Immunization with liposome-anchored pegylated peptides modulates doxorubicin sensitivity in P-glycoprotein-expressing P388 cells</title><author>Gatouillat, Grégory ; Odot, Johann ; Balasse, Emilie ; Nicolau, Claude ; Tosi, Pierre-François ; Hickman, David T ; López-Deber, María Pilar ; Madoulet, Claudie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-6e32e9efef1dc3b565a04811613e054bde787efd0012f2e5b8be23c4ff8667ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibiotics, Antineoplastic - metabolism</topic><topic>Antibiotics, Antineoplastic - pharmacokinetics</topic><topic>Antibiotics, Antineoplastic - pharmacology</topic><topic>Antibodies - administration & dosage</topic><topic>Antibodies - immunology</topic><topic>Antibodies - pharmacology</topic><topic>ATP-Binding Cassette, Sub-Family B, Member 1 - chemistry</topic><topic>ATP-Binding Cassette, Sub-Family B, Member 1 - immunology</topic><topic>ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism</topic><topic>Blotting, Western</topic><topic>Cancer</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Cholesterol</topic><topic>Dilution</topic><topic>Dimensional analysis</topic><topic>Doxorubicin - metabolism</topic><topic>Doxorubicin - pharmacokinetics</topic><topic>Doxorubicin - pharmacology</topic><topic>Drug Resistance, Bacterial</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Hypotheses</topic><topic>Immunization</topic><topic>Immunization - methods</topic><topic>Liposomes</topic><topic>Liposomes - chemistry</topic><topic>Mice</topic><topic>Mice, Inbred Strains</topic><topic>Molecular Sequence Data</topic><topic>Molecular weight</topic><topic>Multidrug resistance</topic><topic>Neoplasms, Experimental - immunology</topic><topic>Neoplasms, Experimental - pathology</topic><topic>Neoplasms, Experimental - prevention & control</topic><topic>P-Glycoprotein</topic><topic>Pegylated peptides</topic><topic>Peptides</topic><topic>Peptides - chemistry</topic><topic>Peptides - immunology</topic><topic>Polyethylene Glycols - chemistry</topic><topic>Proteins</topic><topic>Studies</topic><topic>Survival Analysis</topic><topic>Tumors</topic><topic>Vaccines, Subunit - administration & dosage</topic><topic>Vaccines, Subunit - chemistry</topic><topic>Vaccines, Subunit - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gatouillat, Grégory</creatorcontrib><creatorcontrib>Odot, Johann</creatorcontrib><creatorcontrib>Balasse, Emilie</creatorcontrib><creatorcontrib>Nicolau, Claude</creatorcontrib><creatorcontrib>Tosi, Pierre-François</creatorcontrib><creatorcontrib>Hickman, David T</creatorcontrib><creatorcontrib>López-Deber, María Pilar</creatorcontrib><creatorcontrib>Madoulet, Claudie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gatouillat, Grégory</au><au>Odot, Johann</au><au>Balasse, Emilie</au><au>Nicolau, Claude</au><au>Tosi, Pierre-François</au><au>Hickman, David T</au><au>López-Deber, María Pilar</au><au>Madoulet, Claudie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunization with liposome-anchored pegylated peptides modulates doxorubicin sensitivity in P-glycoprotein-expressing P388 cells</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2007-11-18</date><risdate>2007</risdate><volume>257</volume><issue>2</issue><spage>165</spage><epage>171</epage><pages>165-171</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><abstract>Abstract The clinical use of chemotherapy in cancer treatment is limited by the occurrence of multidrug resistance (MDR) associated with the overexpression of membrane transporters, one of the best known is P-glycoprotein (Pgp), that actively expels drugs out of tumor cells. To overcome Pgp-mediated MDR, synthetic peptides corresponding to fragments from extracellular loops 1, 2 and 4 of the murine Pgp were coupled to polyethylene glycol–distearoylphosphatidylethanolamine and inserted into empty or monophosphoryl lipid A-containing liposomes. This formulation elicited specific antibodies which blocked Pgp-mediated efflux of doxorubicin, resulting in increased intracellular drug accumulation and subsequent potentiation of the cytotoxic effect of doxorubicin on multidrug-resistant P388 (P388R) cells. Previous immunizations with MDR1 peptides improved the efficiency of chemotherapy against P388R cells in vivo , with an increase of 83% of mice survival time. Overall, these results suggest that this approach can modulate Pgp activity by blocking drug efflux and may have clinical relevance as an alternative strategy to toxic chemosensitizers in drug-resistant cancer therapy.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>17517470</pmid><doi>10.1016/j.canlet.2007.04.001</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0304-3835 |
| ispartof | Cancer letters, 2007-11, Vol.257 (2), p.165-171 |
| issn | 0304-3835 1872-7980 |
| language | eng |
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| source | MEDLINE; ScienceDirect Freedom Collection (Elsevier) |
| subjects | Amino Acid Sequence Animals Antibiotics, Antineoplastic - metabolism Antibiotics, Antineoplastic - pharmacokinetics Antibiotics, Antineoplastic - pharmacology Antibodies - administration & dosage Antibodies - immunology Antibodies - pharmacology ATP-Binding Cassette, Sub-Family B, Member 1 - chemistry ATP-Binding Cassette, Sub-Family B, Member 1 - immunology ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism Blotting, Western Cancer Cell Line, Tumor Cell Survival - drug effects Cholesterol Dilution Dimensional analysis Doxorubicin - metabolism Doxorubicin - pharmacokinetics Doxorubicin - pharmacology Drug Resistance, Bacterial Female Flow Cytometry Hematology, Oncology and Palliative Medicine Hypotheses Immunization Immunization - methods Liposomes Liposomes - chemistry Mice Mice, Inbred Strains Molecular Sequence Data Molecular weight Multidrug resistance Neoplasms, Experimental - immunology Neoplasms, Experimental - pathology Neoplasms, Experimental - prevention & control P-Glycoprotein Pegylated peptides Peptides Peptides - chemistry Peptides - immunology Polyethylene Glycols - chemistry Proteins Studies Survival Analysis Tumors Vaccines, Subunit - administration & dosage Vaccines, Subunit - chemistry Vaccines, Subunit - immunology |
| title | Immunization with liposome-anchored pegylated peptides modulates doxorubicin sensitivity in P-glycoprotein-expressing P388 cells |
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