Prostate-Restricted Replicative Adenovirus Expressing Human Endostatin-Angiostatin Fusion Gene Exhibiting Dramatic Antitumor Efficacy
Purpose: Our previous studies coadministering a replication-deficient adenovirus expressing endostatin and angiostatin fusion gene (EndoAngio) and a prostate-restricted, replication-competent adenovirus (PRRA) showed dramatic antitumor efficacy. This study integrated EndoAngio with an improved PRRA...
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| Veröffentlicht in: | Clinical cancer research 2008-01, Vol.14 (1), p.291-299 |
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| creator | XIONG LI LIU, You-Hong LEE, Sang-Jin GARDNER, Thomas A JENG, Meei-Huey CHINGHAI KAO |
| description | Purpose: Our previous studies coadministering a replication-deficient adenovirus expressing endostatin and angiostatin fusion gene
(EndoAngio) and a prostate-restricted, replication-competent adenovirus (PRRA) showed dramatic antitumor efficacy. This study
integrated EndoAngio with an improved PRRA vector to make a single antiangiogenic PRRA, thereby exerting a similarly dramatic
antitumor effect with feasibility for future clinical trials.
Experimental Design: We developed an antiangiogenic PRRA with structural improvements. The antitumor efficacy of EndoAngio-PRRA was evaluated
in prostate-specific antigen/prostate-specific membrane antigen (PSA/PSMA)-positive, androgen-independent CWR22rv tumor models.
The tumor vasculature and cell morphology were observed by dual-photon microscopy. The antiangiogenic effect of EndoAngio
delivered by PRRA and the killing activity of EndoAngio-PRRA were evaluated in vitro . Virus-inactivated conditioned media from virus-infected PSA/PSMA-positive cells were tested for apoptosis induction in prostate
cancer cells.
Results: Our novel EndoAngio-PRRA is a strong antiangiogenic and antitumor agent. Nine of 10 CWR22rv tumors treated by EndoAngio-PRRA
completely regressed, with 1 tumor remaining in a dormant status for 26 weeks after treatment. Dual-photon microscopy revealed
that EndoAngio-PRRA not only inhibited the development of tumor vasculature but also induced apoptosis in tumor cells. Subsequent
in vitro study indicated that EndoAngio-PRRA exhibited stronger tumor-specific killing activity than enhanced green fluorescent protein-PRRA,
which expresses enhanced green fluorescent protein instead of EndoAngio. Virus-inactivated conditioned medium from EndoAngio-PRRA–infected
PSA/PSMA-positive cells induced apoptosis in C4-2 and CWR22rv cells.
Conclusions: EndoAngio-PRRA uniquely combines three distinct antitumor effects to eliminate androgen-independent prostate cancer: antiangiogenesis,
viral oncolysis, and apoptosis. This novel antiangiogenic PRRA represents a powerful agent feasible for future clinical trials
for prostate cancer therapy. |
| doi_str_mv | 10.1158/1078-0432.CCR-07-0867 |
| format | Article |
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(EndoAngio) and a prostate-restricted, replication-competent adenovirus (PRRA) showed dramatic antitumor efficacy. This study
integrated EndoAngio with an improved PRRA vector to make a single antiangiogenic PRRA, thereby exerting a similarly dramatic
antitumor effect with feasibility for future clinical trials.
Experimental Design: We developed an antiangiogenic PRRA with structural improvements. The antitumor efficacy of EndoAngio-PRRA was evaluated
in prostate-specific antigen/prostate-specific membrane antigen (PSA/PSMA)-positive, androgen-independent CWR22rv tumor models.
The tumor vasculature and cell morphology were observed by dual-photon microscopy. The antiangiogenic effect of EndoAngio
delivered by PRRA and the killing activity of EndoAngio-PRRA were evaluated in vitro . Virus-inactivated conditioned media from virus-infected PSA/PSMA-positive cells were tested for apoptosis induction in prostate
cancer cells.
Results: Our novel EndoAngio-PRRA is a strong antiangiogenic and antitumor agent. Nine of 10 CWR22rv tumors treated by EndoAngio-PRRA
completely regressed, with 1 tumor remaining in a dormant status for 26 weeks after treatment. Dual-photon microscopy revealed
that EndoAngio-PRRA not only inhibited the development of tumor vasculature but also induced apoptosis in tumor cells. Subsequent
in vitro study indicated that EndoAngio-PRRA exhibited stronger tumor-specific killing activity than enhanced green fluorescent protein-PRRA,
which expresses enhanced green fluorescent protein instead of EndoAngio. Virus-inactivated conditioned medium from EndoAngio-PRRA–infected
PSA/PSMA-positive cells induced apoptosis in C4-2 and CWR22rv cells.
Conclusions: EndoAngio-PRRA uniquely combines three distinct antitumor effects to eliminate androgen-independent prostate cancer: antiangiogenesis,
viral oncolysis, and apoptosis. This novel antiangiogenic PRRA represents a powerful agent feasible for future clinical trials
for prostate cancer therapy.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-07-0867</identifier><identifier>PMID: 18172281</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adenoviridae - genetics ; Adenovirus ; Angiogenesis Inhibitors - physiology ; angiostatin ; Angiostatins - genetics ; Animals ; Antiangiogenesis ; Antineoplastic agents ; apoptosis ; Artificial Gene Fusion ; Biological and medical sciences ; Blotting, Western ; endostatin ; Endostatins - genetics ; Flow Cytometry ; gene therapy ; Genetic Therapy - methods ; Genetic Vectors ; Humans ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Medical sciences ; Mice ; Mice, Nude ; oncolytic adenovirus ; Pharmacology. Drug treatments ; prostate cancer ; Prostatic Neoplasms - therapy ; Recombinant Fusion Proteins</subject><ispartof>Clinical cancer research, 2008-01, Vol.14 (1), p.291-299</ispartof><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-e24f1120e12bd7c2698205623aa3442ad4985c55d40a48ed3788ed9da69747d3</citedby><cites>FETCH-LOGICAL-c400t-e24f1120e12bd7c2698205623aa3442ad4985c55d40a48ed3788ed9da69747d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,3345,4012,27910,27911,27912</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20145601$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18172281$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>XIONG LI</creatorcontrib><creatorcontrib>LIU, You-Hong</creatorcontrib><creatorcontrib>LEE, Sang-Jin</creatorcontrib><creatorcontrib>GARDNER, Thomas A</creatorcontrib><creatorcontrib>JENG, Meei-Huey</creatorcontrib><creatorcontrib>CHINGHAI KAO</creatorcontrib><title>Prostate-Restricted Replicative Adenovirus Expressing Human Endostatin-Angiostatin Fusion Gene Exhibiting Dramatic Antitumor Efficacy</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: Our previous studies coadministering a replication-deficient adenovirus expressing endostatin and angiostatin fusion gene
(EndoAngio) and a prostate-restricted, replication-competent adenovirus (PRRA) showed dramatic antitumor efficacy. This study
integrated EndoAngio with an improved PRRA vector to make a single antiangiogenic PRRA, thereby exerting a similarly dramatic
antitumor effect with feasibility for future clinical trials.
Experimental Design: We developed an antiangiogenic PRRA with structural improvements. The antitumor efficacy of EndoAngio-PRRA was evaluated
in prostate-specific antigen/prostate-specific membrane antigen (PSA/PSMA)-positive, androgen-independent CWR22rv tumor models.
The tumor vasculature and cell morphology were observed by dual-photon microscopy. The antiangiogenic effect of EndoAngio
delivered by PRRA and the killing activity of EndoAngio-PRRA were evaluated in vitro . Virus-inactivated conditioned media from virus-infected PSA/PSMA-positive cells were tested for apoptosis induction in prostate
cancer cells.
Results: Our novel EndoAngio-PRRA is a strong antiangiogenic and antitumor agent. Nine of 10 CWR22rv tumors treated by EndoAngio-PRRA
completely regressed, with 1 tumor remaining in a dormant status for 26 weeks after treatment. Dual-photon microscopy revealed
that EndoAngio-PRRA not only inhibited the development of tumor vasculature but also induced apoptosis in tumor cells. Subsequent
in vitro study indicated that EndoAngio-PRRA exhibited stronger tumor-specific killing activity than enhanced green fluorescent protein-PRRA,
which expresses enhanced green fluorescent protein instead of EndoAngio. Virus-inactivated conditioned medium from EndoAngio-PRRA–infected
PSA/PSMA-positive cells induced apoptosis in C4-2 and CWR22rv cells.
Conclusions: EndoAngio-PRRA uniquely combines three distinct antitumor effects to eliminate androgen-independent prostate cancer: antiangiogenesis,
viral oncolysis, and apoptosis. This novel antiangiogenic PRRA represents a powerful agent feasible for future clinical trials
for prostate cancer therapy.</description><subject>Adenoviridae - genetics</subject><subject>Adenovirus</subject><subject>Angiogenesis Inhibitors - physiology</subject><subject>angiostatin</subject><subject>Angiostatins - genetics</subject><subject>Animals</subject><subject>Antiangiogenesis</subject><subject>Antineoplastic agents</subject><subject>apoptosis</subject><subject>Artificial Gene Fusion</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>endostatin</subject><subject>Endostatins - genetics</subject><subject>Flow Cytometry</subject><subject>gene therapy</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>In Situ Nick-End Labeling</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>oncolytic adenovirus</subject><subject>Pharmacology. Drug treatments</subject><subject>prostate cancer</subject><subject>Prostatic Neoplasms - therapy</subject><subject>Recombinant Fusion Proteins</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkdFuFCEUhidGY2v1ETTcqFdUYGBgLjfrtjVpotn0nrBwZhczw6zAVPsAfe8y7qiX3sBJzvdzcviq6i0ll5QK9YkSqTDhNbtcr7eYSExUI59V51QIiWvWiOel_sOcVa9S-k4I5ZTwl9UZVVQypuh59fgtjimbDHgLKUdvMzi0hWPvrcn-HtDKQRjvfZwS2vw6RkjJhz26mQYT0Ca432Ef8Crs_VKjqyn5MaBrCFAyB7_zec58jmYofYtWIfs8DWNEm64rc-zD6-pFZ_oEb5b7orq72tytb_Dt1-sv69UttpyQjIHxjlJGgLKdk5Y1rWJENKw2puacGcdbJawQjhPDFbhaqnK2zjSt5NLVF9WH07PHOP6Yyr568MlC35sA45S0JFQK1dL_goy0jCvWFFCcQFu-MUXo9DH6wcQHTYmePenZgZ4d6OJJE6lnTyX3bhkw7QZw_1KLmAK8XwCTrOm7aIL16S_HikrRkJn7eOIOfn_46SNoW0iIRRSYaA-ack01Kzs9AQpZqwY</recordid><startdate>20080101</startdate><enddate>20080101</enddate><creator>XIONG LI</creator><creator>LIU, You-Hong</creator><creator>LEE, Sang-Jin</creator><creator>GARDNER, Thomas A</creator><creator>JENG, Meei-Huey</creator><creator>CHINGHAI KAO</creator><general>American Association for Cancer Research</general><scope>IQODW</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20080101</creationdate><title>Prostate-Restricted Replicative Adenovirus Expressing Human Endostatin-Angiostatin Fusion Gene Exhibiting Dramatic Antitumor Efficacy</title><author>XIONG LI ; LIU, You-Hong ; LEE, Sang-Jin ; GARDNER, Thomas A ; JENG, Meei-Huey ; CHINGHAI KAO</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c400t-e24f1120e12bd7c2698205623aa3442ad4985c55d40a48ed3788ed9da69747d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adenoviridae - genetics</topic><topic>Adenovirus</topic><topic>Angiogenesis Inhibitors - physiology</topic><topic>angiostatin</topic><topic>Angiostatins - genetics</topic><topic>Animals</topic><topic>Antiangiogenesis</topic><topic>Antineoplastic agents</topic><topic>apoptosis</topic><topic>Artificial Gene Fusion</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>endostatin</topic><topic>Endostatins - genetics</topic><topic>Flow Cytometry</topic><topic>gene therapy</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>In Situ Nick-End Labeling</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>oncolytic adenovirus</topic><topic>Pharmacology. Drug treatments</topic><topic>prostate cancer</topic><topic>Prostatic Neoplasms - therapy</topic><topic>Recombinant Fusion Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>XIONG LI</creatorcontrib><creatorcontrib>LIU, You-Hong</creatorcontrib><creatorcontrib>LEE, Sang-Jin</creatorcontrib><creatorcontrib>GARDNER, Thomas A</creatorcontrib><creatorcontrib>JENG, Meei-Huey</creatorcontrib><creatorcontrib>CHINGHAI KAO</creatorcontrib><collection>Pascal-Francis</collection><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>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>XIONG LI</au><au>LIU, You-Hong</au><au>LEE, Sang-Jin</au><au>GARDNER, Thomas A</au><au>JENG, Meei-Huey</au><au>CHINGHAI KAO</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prostate-Restricted Replicative Adenovirus Expressing Human Endostatin-Angiostatin Fusion Gene Exhibiting Dramatic Antitumor Efficacy</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2008-01-01</date><risdate>2008</risdate><volume>14</volume><issue>1</issue><spage>291</spage><epage>299</epage><pages>291-299</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: Our previous studies coadministering a replication-deficient adenovirus expressing endostatin and angiostatin fusion gene
(EndoAngio) and a prostate-restricted, replication-competent adenovirus (PRRA) showed dramatic antitumor efficacy. This study
integrated EndoAngio with an improved PRRA vector to make a single antiangiogenic PRRA, thereby exerting a similarly dramatic
antitumor effect with feasibility for future clinical trials.
Experimental Design: We developed an antiangiogenic PRRA with structural improvements. The antitumor efficacy of EndoAngio-PRRA was evaluated
in prostate-specific antigen/prostate-specific membrane antigen (PSA/PSMA)-positive, androgen-independent CWR22rv tumor models.
The tumor vasculature and cell morphology were observed by dual-photon microscopy. The antiangiogenic effect of EndoAngio
delivered by PRRA and the killing activity of EndoAngio-PRRA were evaluated in vitro . Virus-inactivated conditioned media from virus-infected PSA/PSMA-positive cells were tested for apoptosis induction in prostate
cancer cells.
Results: Our novel EndoAngio-PRRA is a strong antiangiogenic and antitumor agent. Nine of 10 CWR22rv tumors treated by EndoAngio-PRRA
completely regressed, with 1 tumor remaining in a dormant status for 26 weeks after treatment. Dual-photon microscopy revealed
that EndoAngio-PRRA not only inhibited the development of tumor vasculature but also induced apoptosis in tumor cells. Subsequent
in vitro study indicated that EndoAngio-PRRA exhibited stronger tumor-specific killing activity than enhanced green fluorescent protein-PRRA,
which expresses enhanced green fluorescent protein instead of EndoAngio. Virus-inactivated conditioned medium from EndoAngio-PRRA–infected
PSA/PSMA-positive cells induced apoptosis in C4-2 and CWR22rv cells.
Conclusions: EndoAngio-PRRA uniquely combines three distinct antitumor effects to eliminate androgen-independent prostate cancer: antiangiogenesis,
viral oncolysis, and apoptosis. This novel antiangiogenic PRRA represents a powerful agent feasible for future clinical trials
for prostate cancer therapy.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>18172281</pmid><doi>10.1158/1078-0432.CCR-07-0867</doi><tpages>9</tpages></addata></record> |
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| ispartof | Clinical cancer research, 2008-01, Vol.14 (1), p.291-299 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research; Alma/SFX Local Collection |
| subjects | Adenoviridae - genetics Adenovirus Angiogenesis Inhibitors - physiology angiostatin Angiostatins - genetics Animals Antiangiogenesis Antineoplastic agents apoptosis Artificial Gene Fusion Biological and medical sciences Blotting, Western endostatin Endostatins - genetics Flow Cytometry gene therapy Genetic Therapy - methods Genetic Vectors Humans Immunohistochemistry In Situ Nick-End Labeling Male Medical sciences Mice Mice, Nude oncolytic adenovirus Pharmacology. Drug treatments prostate cancer Prostatic Neoplasms - therapy Recombinant Fusion Proteins |
| title | Prostate-Restricted Replicative Adenovirus Expressing Human Endostatin-Angiostatin Fusion Gene Exhibiting Dramatic Antitumor Efficacy |
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