Induction of therapeutic antitumor antiangiogenesis by intratumoral injection of genetically engineered endostatin-producing Semliki Forest virus
Antiangiogenic therapy using Semliki Forest virus (SFV) carrying Endostatin gene for malignant brain tumor was investigated to improve the therapeutic efficacy. The efficiency of SFV-mediated gene delivery was first evaluated for B 16 cells and compared with the efficiency in cells of endothelial or...
Gespeichert in:
| Veröffentlicht in: | Cancer gene therapy 2001-10, Vol.8 (10), p.796-802 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 802 |
|---|---|
| container_issue | 10 |
| container_start_page | 796 |
| container_title | Cancer gene therapy |
| container_volume | 8 |
| creator | Yamanaka, R Zullo, S A Ramsey, J Onodera, M Tanaka, R Blaese, M Xanthopoulos, K G |
| description | Antiangiogenic therapy using Semliki Forest virus (SFV) carrying Endostatin gene for malignant brain tumor was investigated to improve the therapeutic efficacy. The efficiency of SFV-mediated gene delivery was first evaluated for B 16 cells and compared with the efficiency in cells of endothelial origin (HMVECs). HMVECs are more susceptible to SFV infection than B 16 cells. For the in vivo treatment model, phosphate-buffered saline, SFV-LacZ, retrovirus vector GCsap-Endostatin, and SFV-Endostatin were injected to mice bearing B 16 brain tumors. A very significant inhibition of tumor growth was observed in the group that had been treated with SFV-Endostatin. A marked reduction of intratumoral vascularization was seen in the tumor sections from the SFV-Endostatin group compared with tumor sections from the SFV-LacZ or GCsap-Endostatin groups. Moreover, at day 7 after intravenous administration of SFV-Endostatin, the serum level of endostatin was augmented more than 3-fold compared to that after intravenous administration of GCsap-Endostatin. The results indicated that treatment with SFV-Endostatin inhibited the angiogenesis with established tumors. Gene therapy with Endostatin delivered via SFV may be a candidate for the development of new therapy for brain tumors. |
| doi_str_mv | 10.1038/sj.cgt.7700367 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_72243749</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>998143641</sourcerecordid><originalsourceid>FETCH-LOGICAL-c512t-a84cd830b02469da2668b6a92a50ebe9d0709643613ee86d0725c53a263cef853</originalsourceid><addsrcrecordid>eNqFkcuKFDEUhoMoTju6dSlBwV21uVUuSxkcHRhwoa5DKnW6TVmVtElK6MfwjU3PNAqCuMq5fOc_J_wIPadkSwnXb8q09fu6VYoQLtUDtKFCya7vCXmINsQw01FD-AV6UspESGsq_hhdUCq1avUN-nkTx9XXkCJOO1y_QnYHWGvw2MUa6rqkfBe5uA9pDxFKKHg44hBrdndtN7dkgt8aJ6jNu3k-YmhTESDD2MIxlepqiN0hp7YzxD3-BMscvgV8nTKUin-EvJan6NHOzQWend9L9OX63eerD93tx_c3V29vO99TVjunhR81JwNhQprRMSn1IJ1hricwgBmJIkYKLikH0LKlrPc9bxz3sNM9v0Sv73XbOd_Xtt4uoXiYZxchrcUqxgRXwvwXpJopQhlv4Ku_wCmtObZPWCYFVZRoQRv18p8UVUIbxU_Hbe8hn1MpGXb2kMPi8tFSYk_G2zLZZrw9G98GXpxV12GB8Q9-dpr_AnOFrLc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>217489735</pqid></control><display><type>article</type><title>Induction of therapeutic antitumor antiangiogenesis by intratumoral injection of genetically engineered endostatin-producing Semliki Forest virus</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Yamanaka, R ; Zullo, S A ; Ramsey, J ; Onodera, M ; Tanaka, R ; Blaese, M ; Xanthopoulos, K G</creator><creatorcontrib>Yamanaka, R ; Zullo, S A ; Ramsey, J ; Onodera, M ; Tanaka, R ; Blaese, M ; Xanthopoulos, K G</creatorcontrib><description>Antiangiogenic therapy using Semliki Forest virus (SFV) carrying Endostatin gene for malignant brain tumor was investigated to improve the therapeutic efficacy. The efficiency of SFV-mediated gene delivery was first evaluated for B 16 cells and compared with the efficiency in cells of endothelial origin (HMVECs). HMVECs are more susceptible to SFV infection than B 16 cells. For the in vivo treatment model, phosphate-buffered saline, SFV-LacZ, retrovirus vector GCsap-Endostatin, and SFV-Endostatin were injected to mice bearing B 16 brain tumors. A very significant inhibition of tumor growth was observed in the group that had been treated with SFV-Endostatin. A marked reduction of intratumoral vascularization was seen in the tumor sections from the SFV-Endostatin group compared with tumor sections from the SFV-LacZ or GCsap-Endostatin groups. Moreover, at day 7 after intravenous administration of SFV-Endostatin, the serum level of endostatin was augmented more than 3-fold compared to that after intravenous administration of GCsap-Endostatin. The results indicated that treatment with SFV-Endostatin inhibited the angiogenesis with established tumors. Gene therapy with Endostatin delivered via SFV may be a candidate for the development of new therapy for brain tumors.</description><identifier>ISSN: 0929-1903</identifier><identifier>EISSN: 1476-5500</identifier><identifier>DOI: 10.1038/sj.cgt.7700367</identifier><identifier>PMID: 11687903</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Angiogenesis ; Animals ; antiangiogenic factors ; Brain cancer ; Brain Neoplasms - blood supply ; Brain Neoplasms - therapy ; Brain Neoplasms - virology ; Brain tumors ; Cells, Cultured ; Collagen - blood ; Collagen - genetics ; Endostatin ; Endostatins ; Endothelium, Vascular - metabolism ; Endothelium, Vascular - virology ; Female ; Gene Expression ; Gene therapy ; Gene transfer ; Gene Transfer Techniques ; Genetic engineering ; Genetic Therapy - methods ; Genetic Vectors - administration & dosage ; Humans ; Intravenous administration ; Melanoma, Experimental - blood supply ; Melanoma, Experimental - therapy ; Melanoma, Experimental - virology ; Mice ; Mice, Inbred C57BL ; Mice, Nude ; Neovascularization, Pathologic - therapy ; Peptide Fragments - blood ; Peptide Fragments - genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Semliki Forest virus ; Semliki forest virus - physiology ; Survival Rate ; Tumors ; Vascularization</subject><ispartof>Cancer gene therapy, 2001-10, Vol.8 (10), p.796-802</ispartof><rights>Copyright Nature Publishing Group Oct 2001</rights><rights>Nature America, Inc. 2001.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c512t-a84cd830b02469da2668b6a92a50ebe9d0709643613ee86d0725c53a263cef853</citedby><cites>FETCH-LOGICAL-c512t-a84cd830b02469da2668b6a92a50ebe9d0709643613ee86d0725c53a263cef853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11687903$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamanaka, R</creatorcontrib><creatorcontrib>Zullo, S A</creatorcontrib><creatorcontrib>Ramsey, J</creatorcontrib><creatorcontrib>Onodera, M</creatorcontrib><creatorcontrib>Tanaka, R</creatorcontrib><creatorcontrib>Blaese, M</creatorcontrib><creatorcontrib>Xanthopoulos, K G</creatorcontrib><title>Induction of therapeutic antitumor antiangiogenesis by intratumoral injection of genetically engineered endostatin-producing Semliki Forest virus</title><title>Cancer gene therapy</title><addtitle>Cancer Gene Ther</addtitle><description>Antiangiogenic therapy using Semliki Forest virus (SFV) carrying Endostatin gene for malignant brain tumor was investigated to improve the therapeutic efficacy. The efficiency of SFV-mediated gene delivery was first evaluated for B 16 cells and compared with the efficiency in cells of endothelial origin (HMVECs). HMVECs are more susceptible to SFV infection than B 16 cells. For the in vivo treatment model, phosphate-buffered saline, SFV-LacZ, retrovirus vector GCsap-Endostatin, and SFV-Endostatin were injected to mice bearing B 16 brain tumors. A very significant inhibition of tumor growth was observed in the group that had been treated with SFV-Endostatin. A marked reduction of intratumoral vascularization was seen in the tumor sections from the SFV-Endostatin group compared with tumor sections from the SFV-LacZ or GCsap-Endostatin groups. Moreover, at day 7 after intravenous administration of SFV-Endostatin, the serum level of endostatin was augmented more than 3-fold compared to that after intravenous administration of GCsap-Endostatin. The results indicated that treatment with SFV-Endostatin inhibited the angiogenesis with established tumors. Gene therapy with Endostatin delivered via SFV may be a candidate for the development of new therapy for brain tumors.</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>antiangiogenic factors</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - blood supply</subject><subject>Brain Neoplasms - therapy</subject><subject>Brain Neoplasms - virology</subject><subject>Brain tumors</subject><subject>Cells, Cultured</subject><subject>Collagen - blood</subject><subject>Collagen - genetics</subject><subject>Endostatin</subject><subject>Endostatins</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Endothelium, Vascular - virology</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Gene therapy</subject><subject>Gene transfer</subject><subject>Gene Transfer Techniques</subject><subject>Genetic engineering</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors - administration & dosage</subject><subject>Humans</subject><subject>Intravenous administration</subject><subject>Melanoma, Experimental - blood supply</subject><subject>Melanoma, Experimental - therapy</subject><subject>Melanoma, Experimental - virology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Nude</subject><subject>Neovascularization, Pathologic - therapy</subject><subject>Peptide Fragments - blood</subject><subject>Peptide Fragments - genetics</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Semliki Forest virus</subject><subject>Semliki forest virus - physiology</subject><subject>Survival Rate</subject><subject>Tumors</subject><subject>Vascularization</subject><issn>0929-1903</issn><issn>1476-5500</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkcuKFDEUhoMoTju6dSlBwV21uVUuSxkcHRhwoa5DKnW6TVmVtElK6MfwjU3PNAqCuMq5fOc_J_wIPadkSwnXb8q09fu6VYoQLtUDtKFCya7vCXmINsQw01FD-AV6UspESGsq_hhdUCq1avUN-nkTx9XXkCJOO1y_QnYHWGvw2MUa6rqkfBe5uA9pDxFKKHg44hBrdndtN7dkgt8aJ6jNu3k-YmhTESDD2MIxlepqiN0hp7YzxD3-BMscvgV8nTKUin-EvJan6NHOzQWend9L9OX63eerD93tx_c3V29vO99TVjunhR81JwNhQprRMSn1IJ1hricwgBmJIkYKLikH0LKlrPc9bxz3sNM9v0Sv73XbOd_Xtt4uoXiYZxchrcUqxgRXwvwXpJopQhlv4Ku_wCmtObZPWCYFVZRoQRv18p8UVUIbxU_Hbe8hn1MpGXb2kMPi8tFSYk_G2zLZZrw9G98GXpxV12GB8Q9-dpr_AnOFrLc</recordid><startdate>20011001</startdate><enddate>20011001</enddate><creator>Yamanaka, R</creator><creator>Zullo, S A</creator><creator>Ramsey, J</creator><creator>Onodera, M</creator><creator>Tanaka, R</creator><creator>Blaese, M</creator><creator>Xanthopoulos, K G</creator><general>Nature Publishing Group</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>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7QO</scope><scope>7X8</scope></search><sort><creationdate>20011001</creationdate><title>Induction of therapeutic antitumor antiangiogenesis by intratumoral injection of genetically engineered endostatin-producing Semliki Forest virus</title><author>Yamanaka, R ; Zullo, S A ; Ramsey, J ; Onodera, M ; Tanaka, R ; Blaese, M ; Xanthopoulos, K G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c512t-a84cd830b02469da2668b6a92a50ebe9d0709643613ee86d0725c53a263cef853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Angiogenesis</topic><topic>Animals</topic><topic>antiangiogenic factors</topic><topic>Brain cancer</topic><topic>Brain Neoplasms - blood supply</topic><topic>Brain Neoplasms - therapy</topic><topic>Brain Neoplasms - virology</topic><topic>Brain tumors</topic><topic>Cells, Cultured</topic><topic>Collagen - blood</topic><topic>Collagen - genetics</topic><topic>Endostatin</topic><topic>Endostatins</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Endothelium, Vascular - virology</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Gene therapy</topic><topic>Gene transfer</topic><topic>Gene Transfer Techniques</topic><topic>Genetic engineering</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors - administration & dosage</topic><topic>Humans</topic><topic>Intravenous administration</topic><topic>Melanoma, Experimental - blood supply</topic><topic>Melanoma, Experimental - therapy</topic><topic>Melanoma, Experimental - virology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Nude</topic><topic>Neovascularization, Pathologic - therapy</topic><topic>Peptide Fragments - blood</topic><topic>Peptide Fragments - genetics</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Semliki Forest virus</topic><topic>Semliki forest virus - physiology</topic><topic>Survival Rate</topic><topic>Tumors</topic><topic>Vascularization</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamanaka, R</creatorcontrib><creatorcontrib>Zullo, S A</creatorcontrib><creatorcontrib>Ramsey, J</creatorcontrib><creatorcontrib>Onodera, M</creatorcontrib><creatorcontrib>Tanaka, R</creatorcontrib><creatorcontrib>Blaese, M</creatorcontrib><creatorcontrib>Xanthopoulos, K G</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamanaka, R</au><au>Zullo, S A</au><au>Ramsey, J</au><au>Onodera, M</au><au>Tanaka, R</au><au>Blaese, M</au><au>Xanthopoulos, K G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Induction of therapeutic antitumor antiangiogenesis by intratumoral injection of genetically engineered endostatin-producing Semliki Forest virus</atitle><jtitle>Cancer gene therapy</jtitle><addtitle>Cancer Gene Ther</addtitle><date>2001-10-01</date><risdate>2001</risdate><volume>8</volume><issue>10</issue><spage>796</spage><epage>802</epage><pages>796-802</pages><issn>0929-1903</issn><eissn>1476-5500</eissn><abstract>Antiangiogenic therapy using Semliki Forest virus (SFV) carrying Endostatin gene for malignant brain tumor was investigated to improve the therapeutic efficacy. The efficiency of SFV-mediated gene delivery was first evaluated for B 16 cells and compared with the efficiency in cells of endothelial origin (HMVECs). HMVECs are more susceptible to SFV infection than B 16 cells. For the in vivo treatment model, phosphate-buffered saline, SFV-LacZ, retrovirus vector GCsap-Endostatin, and SFV-Endostatin were injected to mice bearing B 16 brain tumors. A very significant inhibition of tumor growth was observed in the group that had been treated with SFV-Endostatin. A marked reduction of intratumoral vascularization was seen in the tumor sections from the SFV-Endostatin group compared with tumor sections from the SFV-LacZ or GCsap-Endostatin groups. Moreover, at day 7 after intravenous administration of SFV-Endostatin, the serum level of endostatin was augmented more than 3-fold compared to that after intravenous administration of GCsap-Endostatin. The results indicated that treatment with SFV-Endostatin inhibited the angiogenesis with established tumors. Gene therapy with Endostatin delivered via SFV may be a candidate for the development of new therapy for brain tumors.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>11687903</pmid><doi>10.1038/sj.cgt.7700367</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0929-1903 |
| ispartof | Cancer gene therapy, 2001-10, Vol.8 (10), p.796-802 |
| issn | 0929-1903 1476-5500 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_72243749 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Angiogenesis Animals antiangiogenic factors Brain cancer Brain Neoplasms - blood supply Brain Neoplasms - therapy Brain Neoplasms - virology Brain tumors Cells, Cultured Collagen - blood Collagen - genetics Endostatin Endostatins Endothelium, Vascular - metabolism Endothelium, Vascular - virology Female Gene Expression Gene therapy Gene transfer Gene Transfer Techniques Genetic engineering Genetic Therapy - methods Genetic Vectors - administration & dosage Humans Intravenous administration Melanoma, Experimental - blood supply Melanoma, Experimental - therapy Melanoma, Experimental - virology Mice Mice, Inbred C57BL Mice, Nude Neovascularization, Pathologic - therapy Peptide Fragments - blood Peptide Fragments - genetics Reverse Transcriptase Polymerase Chain Reaction Semliki Forest virus Semliki forest virus - physiology Survival Rate Tumors Vascularization |
| title | Induction of therapeutic antitumor antiangiogenesis by intratumoral injection of genetically engineered endostatin-producing Semliki Forest virus |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T13%3A12%3A27IST&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=Induction%20of%20therapeutic%20antitumor%20antiangiogenesis%20by%20intratumoral%20injection%20of%20genetically%20engineered%20endostatin-producing%20Semliki%20Forest%20virus&rft.jtitle=Cancer%20gene%20therapy&rft.au=Yamanaka,%20R&rft.date=2001-10-01&rft.volume=8&rft.issue=10&rft.spage=796&rft.epage=802&rft.pages=796-802&rft.issn=0929-1903&rft.eissn=1476-5500&rft_id=info:doi/10.1038/sj.cgt.7700367&rft_dat=%3Cproquest_cross%3E998143641%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=217489735&rft_id=info:pmid/11687903&rfr_iscdi=true |