Copper-67 Radioimmunotherapy and Growth Inhibition by Anti–L1-Cell Adhesion Molecule Monoclonal Antibodies in a Therapy Model of Ovarian Cancer Metastasis
Purpose: We examined the tumor-targeting and therapeutic effects of 67 Cu-labeled single amino acid mutant forms of anti-L1 monoclonal antibody chCE7 in nude mice with orthotopically implanted SKOV3ip human ovarian carcinoma cells. Experimental Design: For radioimmunotherapy, chCE7 antibodies with a...
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| Veröffentlicht in: | Clinical cancer research 2007-01, Vol.13 (2), p.603-611 |
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| creator | Knogler, Karin Grünberg, Jürgen Zimmermann, Kurt Cohrs, Susan Honer, Michael Ametamey, Simon Altevogt, Peter Fogel, Mina Schubiger, P August Novak-Hofer, Ilse |
| description | Purpose: We examined the tumor-targeting and therapeutic effects of 67 Cu-labeled single amino acid mutant forms of anti-L1 monoclonal antibody chCE7 in nude mice with orthotopically implanted
SKOV3ip human ovarian carcinoma cells.
Experimental Design: For radioimmunotherapy, chCE7 antibodies with a mutation of histidine 310 to alanine (chCE7H310A) and a mutation of asparagine
297 to glutamine (chCE7agl) were generated to achieve more rapid blood clearance. Biodistributions of 67 Cu-4-(1,4,8,11-tetraazacyclotetradec-1-yl)-methyl benzoic acid tetrachloride (CPTA)–labeled mutant antibodies were measured
in nude mice bearing SKOV3ip human ovarian cancer metastases. The effects of single i.v. injections of 67 Cu-chCE7agl alone on tumor reduction and survival were investigated. In addition, a combination of low-dose 67 Cu-radioimmunotherapy with unlabeled anti-L1 antibody L1-11A on survival was investigated.
Results: 67 Cu-CPTA-chCE7agl showed high (up to 49% ID/g) and persistent (up to 168 h) uptake in SKOV3ip metastases, with low levels in
normal tissues. 67 Cu-CPTA-chCE7H310A revealed a shorter half-life in the blood and a lower tumor uptake and retention. A single low dose of
4 MBq of 67 Cu-chCE7agl reduced tumor growth but did not prolong survival significantly, whereas a single 10.5 MBq dose of 67 Cu-chCE7agl reduced tumor growth and prolonged survival significantly. The combination of unlabeled monoclonal antibody L1-11A
with a subtherapeutic dose of 67 Cu-radioimmunotherapy also prolonged survival significantly.
Conclusion: The results show improved pharmacokinetics and biodistributions as well as the therapeutic effect of the 67 Cu-labeled single amino acid mutant chCE7agl. Therapeutic data indicate, for the first time, the feasibility of combining
anti–L1-directed growth inhibition and 67 Cu-radioimmunotherapy, thereby increasing the efficiency of antibody treatment of metastatic ovarian carcinoma. |
| doi_str_mv | 10.1158/1078-0432.CCR-06-1486 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_68948005</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20223599</sourcerecordid><originalsourceid>FETCH-LOGICAL-c417t-e5506a27ca3a739941bd2f98dea620a0d5a081beba3132c3dd99d1ca57aed4453</originalsourceid><addsrcrecordid>eNqFkc1u1DAQxyMEoqXwCCCf6MnFH3E-jqsISqVdVarK2ZrYs8QosYOdUO2Nd-iVp-NJSLqLOCJZ8kj-_Wc0_mXZW86uOFfVB87KirJciqumuaOsoDyvimfZOVeqpFIU6vlS_2XOslcpfWOM55zlL7MzXgqlRCXPs19NGEeMtCjJHVgX3DDMPkwdRhgPBLwl1zE8TB258Z1r3eSCJ-2BbPzkfv983HLaYN-Tje0wrU-70KOZe1wKH0wfPPRPbBusw0ScJ0DuT813wWJPwp7c_oDowJMGvMFIdjhBWo5Lr7MXe-gTvjndF9mXTx_vm890e3t902y21OS8nCgqxQoQpQEJpazrnLdW7OvKIhSCAbMKWMVbbEFyKYy0tq4tN6BKQJvnSl5k7499xxi-z5gmPbhklsXAY5iTLqo6rxj7PyiYEFLV9QKqI2hiSCniXo_RDRAPmjO9-tOrG7260Ys_zQq9-lty704D5nZA-y91ErYAl0egc1-7BxdRm6dfi5gQouk0l1rogkn5B7ctpvc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20223599</pqid></control><display><type>article</type><title>Copper-67 Radioimmunotherapy and Growth Inhibition by Anti–L1-Cell Adhesion Molecule Monoclonal Antibodies in a Therapy Model of Ovarian Cancer Metastasis</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>American Association for Cancer Research</source><source>Alma/SFX Local Collection</source><creator>Knogler, Karin ; Grünberg, Jürgen ; Zimmermann, Kurt ; Cohrs, Susan ; Honer, Michael ; Ametamey, Simon ; Altevogt, Peter ; Fogel, Mina ; Schubiger, P August ; Novak-Hofer, Ilse</creator><creatorcontrib>Knogler, Karin ; Grünberg, Jürgen ; Zimmermann, Kurt ; Cohrs, Susan ; Honer, Michael ; Ametamey, Simon ; Altevogt, Peter ; Fogel, Mina ; Schubiger, P August ; Novak-Hofer, Ilse</creatorcontrib><description>Purpose: We examined the tumor-targeting and therapeutic effects of 67 Cu-labeled single amino acid mutant forms of anti-L1 monoclonal antibody chCE7 in nude mice with orthotopically implanted
SKOV3ip human ovarian carcinoma cells.
Experimental Design: For radioimmunotherapy, chCE7 antibodies with a mutation of histidine 310 to alanine (chCE7H310A) and a mutation of asparagine
297 to glutamine (chCE7agl) were generated to achieve more rapid blood clearance. Biodistributions of 67 Cu-4-(1,4,8,11-tetraazacyclotetradec-1-yl)-methyl benzoic acid tetrachloride (CPTA)–labeled mutant antibodies were measured
in nude mice bearing SKOV3ip human ovarian cancer metastases. The effects of single i.v. injections of 67 Cu-chCE7agl alone on tumor reduction and survival were investigated. In addition, a combination of low-dose 67 Cu-radioimmunotherapy with unlabeled anti-L1 antibody L1-11A on survival was investigated.
Results: 67 Cu-CPTA-chCE7agl showed high (up to 49% ID/g) and persistent (up to 168 h) uptake in SKOV3ip metastases, with low levels in
normal tissues. 67 Cu-CPTA-chCE7H310A revealed a shorter half-life in the blood and a lower tumor uptake and retention. A single low dose of
4 MBq of 67 Cu-chCE7agl reduced tumor growth but did not prolong survival significantly, whereas a single 10.5 MBq dose of 67 Cu-chCE7agl reduced tumor growth and prolonged survival significantly. The combination of unlabeled monoclonal antibody L1-11A
with a subtherapeutic dose of 67 Cu-radioimmunotherapy also prolonged survival significantly.
Conclusion: The results show improved pharmacokinetics and biodistributions as well as the therapeutic effect of the 67 Cu-labeled single amino acid mutant chCE7agl. Therapeutic data indicate, for the first time, the feasibility of combining
anti–L1-directed growth inhibition and 67 Cu-radioimmunotherapy, thereby increasing the efficiency of antibody treatment of metastatic ovarian carcinoma.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-06-1486</identifier><identifier>PMID: 17255283</identifier><language>eng</language><publisher>United States: American Association for Cancer Research</publisher><subject>Animals ; anti-L1 antibody chCE7 ; Antibodies, Monoclonal - therapeutic use ; Cell Line, Tumor ; Copper Radioisotopes - therapeutic use ; Copper-67 ; Female ; Humans ; Mice ; Mice, Nude ; Mutation ; Neoplasm Metastasis ; Neural Cell Adhesion Molecule L1 - immunology ; Ovarian Neoplasms - immunology ; Ovarian Neoplasms - pathology ; Ovarian Neoplasms - therapy ; Plasmids - metabolism ; Positron-Emission Tomography - methods ; Radioimmunotherapy ; Radioimmunotherapy - methods</subject><ispartof>Clinical cancer research, 2007-01, Vol.13 (2), p.603-611</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c417t-e5506a27ca3a739941bd2f98dea620a0d5a081beba3132c3dd99d1ca57aed4453</citedby><cites>FETCH-LOGICAL-c417t-e5506a27ca3a739941bd2f98dea620a0d5a081beba3132c3dd99d1ca57aed4453</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,3357,27926,27927</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17255283$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Knogler, Karin</creatorcontrib><creatorcontrib>Grünberg, Jürgen</creatorcontrib><creatorcontrib>Zimmermann, Kurt</creatorcontrib><creatorcontrib>Cohrs, Susan</creatorcontrib><creatorcontrib>Honer, Michael</creatorcontrib><creatorcontrib>Ametamey, Simon</creatorcontrib><creatorcontrib>Altevogt, Peter</creatorcontrib><creatorcontrib>Fogel, Mina</creatorcontrib><creatorcontrib>Schubiger, P August</creatorcontrib><creatorcontrib>Novak-Hofer, Ilse</creatorcontrib><title>Copper-67 Radioimmunotherapy and Growth Inhibition by Anti–L1-Cell Adhesion Molecule Monoclonal Antibodies in a Therapy Model of Ovarian Cancer Metastasis</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: We examined the tumor-targeting and therapeutic effects of 67 Cu-labeled single amino acid mutant forms of anti-L1 monoclonal antibody chCE7 in nude mice with orthotopically implanted
SKOV3ip human ovarian carcinoma cells.
Experimental Design: For radioimmunotherapy, chCE7 antibodies with a mutation of histidine 310 to alanine (chCE7H310A) and a mutation of asparagine
297 to glutamine (chCE7agl) were generated to achieve more rapid blood clearance. Biodistributions of 67 Cu-4-(1,4,8,11-tetraazacyclotetradec-1-yl)-methyl benzoic acid tetrachloride (CPTA)–labeled mutant antibodies were measured
in nude mice bearing SKOV3ip human ovarian cancer metastases. The effects of single i.v. injections of 67 Cu-chCE7agl alone on tumor reduction and survival were investigated. In addition, a combination of low-dose 67 Cu-radioimmunotherapy with unlabeled anti-L1 antibody L1-11A on survival was investigated.
Results: 67 Cu-CPTA-chCE7agl showed high (up to 49% ID/g) and persistent (up to 168 h) uptake in SKOV3ip metastases, with low levels in
normal tissues. 67 Cu-CPTA-chCE7H310A revealed a shorter half-life in the blood and a lower tumor uptake and retention. A single low dose of
4 MBq of 67 Cu-chCE7agl reduced tumor growth but did not prolong survival significantly, whereas a single 10.5 MBq dose of 67 Cu-chCE7agl reduced tumor growth and prolonged survival significantly. The combination of unlabeled monoclonal antibody L1-11A
with a subtherapeutic dose of 67 Cu-radioimmunotherapy also prolonged survival significantly.
Conclusion: The results show improved pharmacokinetics and biodistributions as well as the therapeutic effect of the 67 Cu-labeled single amino acid mutant chCE7agl. Therapeutic data indicate, for the first time, the feasibility of combining
anti–L1-directed growth inhibition and 67 Cu-radioimmunotherapy, thereby increasing the efficiency of antibody treatment of metastatic ovarian carcinoma.</description><subject>Animals</subject><subject>anti-L1 antibody chCE7</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Cell Line, Tumor</subject><subject>Copper Radioisotopes - therapeutic use</subject><subject>Copper-67</subject><subject>Female</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Mutation</subject><subject>Neoplasm Metastasis</subject><subject>Neural Cell Adhesion Molecule L1 - immunology</subject><subject>Ovarian Neoplasms - immunology</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Ovarian Neoplasms - therapy</subject><subject>Plasmids - metabolism</subject><subject>Positron-Emission Tomography - methods</subject><subject>Radioimmunotherapy</subject><subject>Radioimmunotherapy - methods</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAQxyMEoqXwCCCf6MnFH3E-jqsISqVdVarK2ZrYs8QosYOdUO2Nd-iVp-NJSLqLOCJZ8kj-_Wc0_mXZW86uOFfVB87KirJciqumuaOsoDyvimfZOVeqpFIU6vlS_2XOslcpfWOM55zlL7MzXgqlRCXPs19NGEeMtCjJHVgX3DDMPkwdRhgPBLwl1zE8TB258Z1r3eSCJ-2BbPzkfv983HLaYN-Tje0wrU-70KOZe1wKH0wfPPRPbBusw0ScJ0DuT813wWJPwp7c_oDowJMGvMFIdjhBWo5Lr7MXe-gTvjndF9mXTx_vm890e3t902y21OS8nCgqxQoQpQEJpazrnLdW7OvKIhSCAbMKWMVbbEFyKYy0tq4tN6BKQJvnSl5k7499xxi-z5gmPbhklsXAY5iTLqo6rxj7PyiYEFLV9QKqI2hiSCniXo_RDRAPmjO9-tOrG7260Ys_zQq9-lty704D5nZA-y91ErYAl0egc1-7BxdRm6dfi5gQouk0l1rogkn5B7ctpvc</recordid><startdate>20070115</startdate><enddate>20070115</enddate><creator>Knogler, Karin</creator><creator>Grünberg, Jürgen</creator><creator>Zimmermann, Kurt</creator><creator>Cohrs, Susan</creator><creator>Honer, Michael</creator><creator>Ametamey, Simon</creator><creator>Altevogt, Peter</creator><creator>Fogel, Mina</creator><creator>Schubiger, P August</creator><creator>Novak-Hofer, Ilse</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>20070115</creationdate><title>Copper-67 Radioimmunotherapy and Growth Inhibition by Anti–L1-Cell Adhesion Molecule Monoclonal Antibodies in a Therapy Model of Ovarian Cancer Metastasis</title><author>Knogler, Karin ; Grünberg, Jürgen ; Zimmermann, Kurt ; Cohrs, Susan ; Honer, Michael ; Ametamey, Simon ; Altevogt, Peter ; Fogel, Mina ; Schubiger, P August ; Novak-Hofer, Ilse</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-e5506a27ca3a739941bd2f98dea620a0d5a081beba3132c3dd99d1ca57aed4453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>anti-L1 antibody chCE7</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Cell Line, Tumor</topic><topic>Copper Radioisotopes - therapeutic use</topic><topic>Copper-67</topic><topic>Female</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Mutation</topic><topic>Neoplasm Metastasis</topic><topic>Neural Cell Adhesion Molecule L1 - immunology</topic><topic>Ovarian Neoplasms - immunology</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Ovarian Neoplasms - therapy</topic><topic>Plasmids - metabolism</topic><topic>Positron-Emission Tomography - methods</topic><topic>Radioimmunotherapy</topic><topic>Radioimmunotherapy - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Knogler, Karin</creatorcontrib><creatorcontrib>Grünberg, Jürgen</creatorcontrib><creatorcontrib>Zimmermann, Kurt</creatorcontrib><creatorcontrib>Cohrs, Susan</creatorcontrib><creatorcontrib>Honer, Michael</creatorcontrib><creatorcontrib>Ametamey, Simon</creatorcontrib><creatorcontrib>Altevogt, Peter</creatorcontrib><creatorcontrib>Fogel, Mina</creatorcontrib><creatorcontrib>Schubiger, P August</creatorcontrib><creatorcontrib>Novak-Hofer, Ilse</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>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Knogler, Karin</au><au>Grünberg, Jürgen</au><au>Zimmermann, Kurt</au><au>Cohrs, Susan</au><au>Honer, Michael</au><au>Ametamey, Simon</au><au>Altevogt, Peter</au><au>Fogel, Mina</au><au>Schubiger, P August</au><au>Novak-Hofer, Ilse</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Copper-67 Radioimmunotherapy and Growth Inhibition by Anti–L1-Cell Adhesion Molecule Monoclonal Antibodies in a Therapy Model of Ovarian Cancer Metastasis</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2007-01-15</date><risdate>2007</risdate><volume>13</volume><issue>2</issue><spage>603</spage><epage>611</epage><pages>603-611</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: We examined the tumor-targeting and therapeutic effects of 67 Cu-labeled single amino acid mutant forms of anti-L1 monoclonal antibody chCE7 in nude mice with orthotopically implanted
SKOV3ip human ovarian carcinoma cells.
Experimental Design: For radioimmunotherapy, chCE7 antibodies with a mutation of histidine 310 to alanine (chCE7H310A) and a mutation of asparagine
297 to glutamine (chCE7agl) were generated to achieve more rapid blood clearance. Biodistributions of 67 Cu-4-(1,4,8,11-tetraazacyclotetradec-1-yl)-methyl benzoic acid tetrachloride (CPTA)–labeled mutant antibodies were measured
in nude mice bearing SKOV3ip human ovarian cancer metastases. The effects of single i.v. injections of 67 Cu-chCE7agl alone on tumor reduction and survival were investigated. In addition, a combination of low-dose 67 Cu-radioimmunotherapy with unlabeled anti-L1 antibody L1-11A on survival was investigated.
Results: 67 Cu-CPTA-chCE7agl showed high (up to 49% ID/g) and persistent (up to 168 h) uptake in SKOV3ip metastases, with low levels in
normal tissues. 67 Cu-CPTA-chCE7H310A revealed a shorter half-life in the blood and a lower tumor uptake and retention. A single low dose of
4 MBq of 67 Cu-chCE7agl reduced tumor growth but did not prolong survival significantly, whereas a single 10.5 MBq dose of 67 Cu-chCE7agl reduced tumor growth and prolonged survival significantly. The combination of unlabeled monoclonal antibody L1-11A
with a subtherapeutic dose of 67 Cu-radioimmunotherapy also prolonged survival significantly.
Conclusion: The results show improved pharmacokinetics and biodistributions as well as the therapeutic effect of the 67 Cu-labeled single amino acid mutant chCE7agl. Therapeutic data indicate, for the first time, the feasibility of combining
anti–L1-directed growth inhibition and 67 Cu-radioimmunotherapy, thereby increasing the efficiency of antibody treatment of metastatic ovarian carcinoma.</abstract><cop>United States</cop><pub>American Association for Cancer Research</pub><pmid>17255283</pmid><doi>10.1158/1078-0432.CCR-06-1486</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research; Alma/SFX Local Collection |
| subjects | Animals anti-L1 antibody chCE7 Antibodies, Monoclonal - therapeutic use Cell Line, Tumor Copper Radioisotopes - therapeutic use Copper-67 Female Humans Mice Mice, Nude Mutation Neoplasm Metastasis Neural Cell Adhesion Molecule L1 - immunology Ovarian Neoplasms - immunology Ovarian Neoplasms - pathology Ovarian Neoplasms - therapy Plasmids - metabolism Positron-Emission Tomography - methods Radioimmunotherapy Radioimmunotherapy - methods |
| title | Copper-67 Radioimmunotherapy and Growth Inhibition by Anti–L1-Cell Adhesion Molecule Monoclonal Antibodies in a Therapy Model of Ovarian Cancer Metastasis |
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