Conditionally Replicating Adenovirus Expressing TIMP2 Increases Survival in a Mouse Model of Disseminated Ovarian Cancer
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{"title"=>"Conditionally replicating adenovirus expressing TIMP2 increases survival in a mouse model of disseminated ovarian cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Sherry W.", "last_name"=>"Yang", "scopus_author_id"=>"41862677900"}, {"first_name"=>"Diptiman", "last_name"=>"Chanda", "scopus_author_id"=>"16644965800"}, {"first_name"=>"James J.", "last_name"=>"Cody", "scopus_author_id"=>"26025959300"}, {"first_name"=>"Angel A.", "last_name"=>"Rivera", "scopus_author_id"=>"35512652100"}, {"first_name"=>"Reinhard", "last_name"=>"Waehler", "scopus_author_id"=>"13404746600"}, {"first_name"=>"Gene P.", "last_name"=>"Siegal", "scopus_author_id"=>"7006745151"}, {"first_name"=>"Joanne T.", "last_name"=>"Douglas", "scopus_author_id"=>"7403212964"}, {"first_name"=>"Selvarangan", "last_name"=>"Ponnazhagan", "scopus_author_id"=>"7003851226"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"362735273", "sgr"=>"80053947412", "doi"=>"10.1371/journal.pone.0025131", "scopus"=>"2-s2.0-80053947412", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"22022379"}, "id"=>"1ab7774e-f435-34ac-8509-2489303bdbfd", "abstract"=>"Ovarian cancer remains difficult to treat mainly due to presentation of the disease at an advanced stage. Conditionally-replicating adenoviruses (CRAds) are promising anti-cancer agents that selectively kill the tumor cells. The present study evaluated the efficacy of a novel CRAd (Ad5/3-CXCR4-TIMP2) containing the CXCR4 promoter for selective viral replication in cancer cells together with TIMP2 as a therapeutic transgene, targeting the matrix metalloproteases (MMPs) in a murine orthotopic model of disseminated ovarian cancer. An orthotopic model of ovarian cancer was established in athymic nude mice by intraperitonal injection of the human ovarian cancer cell line, SKOV3-Luc, expressing luciferase. Upon confirmation of peritoneal dissemination of the cells by non-invasive imaging, mice were randomly divided into four treatment groups: PBS, Ad-ΔE1-TIMP2, Ad5/3-CXCR4, and Ad5/3-CXCR4-TIMP2. All mice were imaged weekly to monitor tumor growth and were sacrificed upon reaching any of the predefined endpoints, including high tumor burden and significant weight loss along with clinical evidence of pain and distress. Survival analysis was performed using the Log-rank test. The median survival for the PBS cohort was 33 days; for Ad-ΔE1-TIMP2, 39 days; for Ad5/3-CXCR4, 52.5 days; and for Ad5/3-CXCR4-TIMP2, 63 days. The TIMP2-armed CRAd delayed tumor growth and significantly increased survival when compared to the unarmed CRAd. This therapeutic effect was confirmed to be mediated through inhibition of MMP9. Results of the in vivo study support the translational potential of Ad5/3-CXCR4-TIMP2 for treatment of human patients with advanced ovarian cancer.", "link"=>"http://www.mendeley.com/research/conditionally-replicating-adenovirus-expressing-timp2-increases-survival-mouse-model-disseminated-ov", "reader_count"=>13, "reader_count_by_academic_status"=>{"Researcher"=>3, "Student > Ph. D. Student"=>4, "Student > Master"=>2, "Student > Bachelor"=>2, "Professor"=>2}, "reader_count_by_user_role"=>{"Researcher"=>3, "Student > Ph. D. Student"=>4, "Student > Master"=>2, "Student > Bachelor"=>2, "Professor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>3, "Chemistry"=>1, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Chemistry"=>{"Chemistry"=>1}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/725276"], "description"=>"<p>At the time of sacrifice of mice due to tumor burden, tumors were collected from indicated treatment groups and examined for expression of TIMP2 by immunohistochemistry.</p>", "links"=>[], "tags"=>["excised", "epithelial", "ovarian"], "article_id"=>395633, "categories"=>["Cancer", "Genetics"], "users"=>["Sherry W. Yang", "Diptiman Chanda", "James J. Cody", "Angel A. Rivera", "Reinhard Waehler", "Gene P. Siegal", "Joanne T. Douglas", "Selvarangan Ponnazhagan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025131.g004", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TIMP_2_expression_in_excised_epithelial_ovarian_tumor_/395633", "title"=>"TIMP-2 expression in excised epithelial ovarian tumor.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 13:51:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/724987"], "description"=>"<p>Adwt300, is the wild- type Ad5 virus. Ad-ΔE1-TIMP2 is an E1-, E3-deleted replication-deficient Ad5 vector which expresses TIMP2 under the control of the CMV promoter in E1. Ad5/3-CXCR4 is an unarmed CRAd with a CXCR4 promoter in E1 to limit viral replication to the cancer cells in conjunction with a Ad5/3 modified fiber that contains the shaft and tail of Ad5 fiber and the Ad3 fiber knob. Ad5/3-CXCR4-TIMP2 is a CRAd with the CXCR4 promoter in E1, armed with TIMP2 in the E3B region and the aforementioned F5/3 modified fiber.</p>", "links"=>[], "tags"=>["crad"], "article_id"=>395332, "categories"=>["Cancer", "Genetics"], "users"=>["Sherry W. Yang", "Diptiman Chanda", "James J. Cody", "Angel A. Rivera", "Reinhard Waehler", "Gene P. Siegal", "Joanne T. Douglas", "Selvarangan Ponnazhagan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025131.g001", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genomic_organization_of_armed_CRAd_and_control_viruses_/395332", "title"=>"Genomic organization of armed CRAd and control viruses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 13:50:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/725382"], "description"=>"<p>At the time of sacrifice of mice due to tumor burden, tumors were collected from indicated treatment groups and examined for expression of MMP-9 by immunohistochemistry.</p>", "links"=>[], "tags"=>["excised", "epithelial", "ovarian"], "article_id"=>395736, "categories"=>["Cancer", "Genetics"], "users"=>["Sherry W. Yang", "Diptiman Chanda", "James J. Cody", "Angel A. Rivera", "Reinhard Waehler", "Gene P. Siegal", "Joanne T. Douglas", "Selvarangan Ponnazhagan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025131.g005", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MMP_9_expression_in_excised_epithelial_ovarian_tumor_/395736", "title"=>"MMP-9 expression in excised epithelial ovarian tumor.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 13:52:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/725170"], "description"=>"<p>Mice were monitored for survival. Survival data are plotted on a Kaplan-Meier curve (A). Treatment with Ad5/3-CXCR4-TIMP2 significantly enhanced survival when compared to treatment with Ad-ΔE1-TIMP2, Ad5/3-CXCR4, or PBS (p<0.05). (B), median survival in days for each treatment group.</p>", "links"=>[], "tags"=>["genetics and genomics", "oncology"], "article_id"=>395524, "categories"=>["Cancer", "Genetics"], "users"=>["Sherry W. Yang", "Diptiman Chanda", "James J. Cody", "Angel A. Rivera", "Reinhard Waehler", "Gene P. Siegal", "Joanne T. Douglas", "Selvarangan Ponnazhagan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025131.g003", "stats"=>{"downloads"=>2, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Survival_analysis_/395524", "title"=>"Survival analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 13:51:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/725068"], "description"=>"<p>Disseminated tumors were established by injecting 5×10<sup>6</sup> SKOV3-luc cells i.p. into female athymic nude mice on day 0. On day 8, mice were treated with either an i.p. injection of PBS, or 2×10<sup>8</sup> IU of Ad-ΔE1-TIMP2, Ad5/3-CXCR4, and Ad5/3-CXCR4-TIMP2, respectively. Bioluminescence levels were measured weekly. (A), pseudocolor image representing bioluminescence intensity on days 8, 22, 30 and 36. (B), bioluminescence intensity from the abdominal region was quantitated and normalized, and the mean photon counts per second for each group are shown for the given days. Data reported as the mean ± SD for each treatment group. *p<0.05.</p>", "links"=>[], "tags"=>["imaging", "mice"], "article_id"=>395421, "categories"=>["Cancer", "Genetics"], "users"=>["Sherry W. Yang", "Diptiman Chanda", "James J. Cody", "Angel A. Rivera", "Reinhard Waehler", "Gene P. Siegal", "Joanne T. Douglas", "Selvarangan Ponnazhagan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025131.g002", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bioluminescent_imaging_of_mice_before_and_after_treatment_/395421", "title"=>"Bioluminescent imaging of mice before and after treatment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 13:50:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/725504"], "description"=>"<p>Tumor conglomerates in the abdominal area were collected during sacrifice of the animals from indicated treatment groups and fixed. Five µM sections of paraffin blocks of tumor tissues were stained with human CD31 antibody to detect blood vasculature.</p>", "links"=>[], "tags"=>["excised", "epithelial", "ovarian"], "article_id"=>395854, "categories"=>["Cancer", "Genetics"], "users"=>["Sherry W. Yang", "Diptiman Chanda", "James J. Cody", "Angel A. Rivera", "Reinhard Waehler", "Gene P. Siegal", "Joanne T. Douglas", "Selvarangan Ponnazhagan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025131.g006", "stats"=>{"downloads"=>3, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CD31_expression_in_excised_epithelial_ovarian_tumor_/395854", "title"=>"CD31 expression in excised epithelial ovarian tumor.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 13:53:06"}

PMC Usage Stats | Further Information

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Relative Metric

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