Enhanced Antitumor Efficacy of an Oncolytic Herpes Simplex Virus Expressing an Endostatin–Angiostatin Fusion Gene in Human Glioblastoma Stem Cell Xenografts
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{"title"=>"Enhanced antitumor efficacy of an oncolytic herpes simplex virus expressing an endostatin-angiostatin fusion gene in human glioblastoma stem cell xenografts", "type"=>"journal", "authors"=>[{"first_name"=>"Guobin", "last_name"=>"Zhang", "scopus_author_id"=>"55817606500"}, {"first_name"=>"Guishan", "last_name"=>"Jin", "scopus_author_id"=>"7401563134"}, {"first_name"=>"Xiutao", "last_name"=>"Nie", "scopus_author_id"=>"56145614000"}, {"first_name"=>"Ruifang", "last_name"=>"Mi", "scopus_author_id"=>"35211200800"}, {"first_name"=>"Guidong", "last_name"=>"Zhu", "scopus_author_id"=>"55489903200"}, {"first_name"=>"William", "last_name"=>"Jia", "scopus_author_id"=>"55623773800"}, {"first_name"=>"Fusheng", "last_name"=>"Liu", "scopus_author_id"=>"57188590112"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84899690729", "scopus"=>"2-s2.0-84899690729", "issn"=>"19326203", "pmid"=>"24755877", "pui"=>"372991359", "doi"=>"10.1371/journal.pone.0095872"}, "id"=>"84b20729-9294-3fdf-8657-cdbd62f3ba3b", "abstract"=>"Viruses have demonstrated strong potential for the therapeutic targeting of glioblastoma stem cells (GSCs). In this study, the use of a herpes simplex virus carrying endostatin-angiostatin (VAE) as a novel therapeutic targeting strategy for glioblastoma-derived cancer stem cells was investigated. We isolated six stable GSC-enriched cultures from 36 human glioblastoma specimens and selected one of the stable GSCs lines for establishing GSC-carrying orthotopic nude mouse models. The following results were obtained: (a) VAE rapidly proliferated in GSCs and expressed endo-angio in vitro and in vivo 48 h and 10 d after infection, respectively; (b) compared with the control gliomas treated with rHSV or Endostar, the subcutaneous gliomas derived from the GSCs showed a significant reduction in microvessel density after VAE treatment; (c) compared with the control, a significant improvement was observed in the length of the survival of mice with intracranial and subcutaneous gliomas treated with VAE; (d) MRI analysis showed that the tumor volumes of the intracranial gliomas generated by GSCs remarkably decreased after 10 d of VAE treatment compared with the controls. In conclusion, VAE demonstrated oncolytic therapeutic efficacy in animal models of human GSCs and expressed an endostatin-angiostatin fusion gene, which enhanced antitumor efficacy most likely by restricting tumor microvasculature development.", "link"=>"http://www.mendeley.com/research/enhanced-antitumor-efficacy-oncolytic-herpes-simplex-virus-expressing-endostatinangiostatin-fusion-g-1", "reader_count"=>14, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>4, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>4, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>5, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1560383"], "description"=>"<p>(A) RT–PCR results indicated that a significant induction of endo–angio mRNA expression existed after VAE infection in vitro and in vivo. By contrast, only the internal standard control, GAPDH, could be detected in the r-HSV-, Endostar-, and PBS-treated groups. (B) Cell lysates and ECM were harvested 48 h after infection, and the orthotopically implanted tumors were harvested 10 d after injection, as described in the Materials and Methods section. The temporal pattern of the expression of endo–angio was investigated via western blot analysis of cell lysates and ECM for the in vitro experiments, and proteins extracted from the tumors for the in vivo experiments. Western blotting results indicated that a 58 kDa fusion protein recognized by the endostatin antibody was present in the VAE group, but not in the r-HSV group or the Endostar group. β-actin was detectable in all samples.</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "stem cells", "Molecular cell biology", "molecular biology", "Molecular biology techniques", "Gene therapy", "Infectious diseases", "Sexually transmitted diseases", "Herpes simplex", "neurology", "Neurological tumors", "Glioblastoma multiforme", "oncology", "Cancer treatment", "Antiangiogenesis therapy", "Cancers and neoplasms", "Model organisms", "Animal models", "Mouse models", "exogenous", "fusion", "vitro"], "article_id"=>1079677, "categories"=>["Biological Sciences"], "users"=>["Guobin Zhang", "Guishan Jin", "Xiutao Nie", "Ruifang Mi", "Guidong Zhu", "William Jia", "Fusheng Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0095872.g001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_the_exogenous_endo_8211_angio_fusion_gene_and_the_activity_of_the_fusion_protein_in_vitro_and_in_vivo_/1079677", "title"=>"Expression of the exogenous endo–angio fusion gene and the activity of the fusion protein in vitro and in vivo.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-22 11:31:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1560403"], "description"=>"<p>(A) Kaplan–Meier survival curves of mice with subcutaneous GSC-derived tumors treated with PBS, Endostar, r-HSV, or VAE. Mice with subcutaneous GSCs-derived tumors (range = 100 mm<sup>3</sup> to 200 mm<sup>3</sup>) were treated with PBS, Endostar, or 1×10<sup>7</sup> plaque-forming units (p.f.u.) of rHSV or VAE on day 10 (n = 10/group) via direct intratumoral injection. The mice were closely monitored for tumor growth and were killed when their tumors reached 2000 mm<sup>3</sup> or when they lost >20% of their body weight. Mice treated with VAE showed significant improvement in survival compared with mice treated with r-HSV or Endostar (P<0.001). (B) Kaplan–Meier survival curve for mice with intracranial GSC-derived tumors treated with PBS, Endostar, r-HSV, or VAE. Athymic nude mice bearing intracranial GSC-derived tumors were treated with PBS, Endostar, or 2×10<sup>6</sup> p.f.u. of r-HSV or VAE 10 d after tumor cell implantation. The mice were then closely monitored for survival. Note the statistically significant improvement in median survival of mice treated with VAE compared with r-HSV- and Endostar-treated mice (P<0.001). (C) In a separate intracranial glioma experiment, mice were treated with VAE, r-HSV, Endostar, or PBS on day 10 after tumor cell implantation and examined on days 10, 20, 30, and 40 via MRI. Representative images of MRI T2-axial sections indicating the changes in tumor size (red arrows) after treatment with VAE, rHSV, Endostar, or PBS are shown. Note that all animals in the PBS-treated group developed large tumors during the treatment period. VAE-treated mice underwent complete remission, and the r-HSV- and Endostar-treated groups exhibited stable disease on day 20. After day 20, residual tumors in the VAE-treated mice regrew, and tumors in r-HSV- and Endostar-treated mice rapidly worsened (see results on day 30).</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "stem cells", "Molecular cell biology", "molecular biology", "Molecular biology techniques", "Gene therapy", "Infectious diseases", "Sexually transmitted diseases", "Herpes simplex", "neurology", "Neurological tumors", "Glioblastoma multiforme", "oncology", "Cancer treatment", "Antiangiogenesis therapy", "Cancers and neoplasms", "Model organisms", "Animal models", "Mouse models", "anti-tumor", "efficacy", "vae", "compared"], "article_id"=>1079694, "categories"=>["Biological Sciences"], "users"=>["Guobin Zhang", "Guishan Jin", "Xiutao Nie", "Ruifang Mi", "Guidong Zhu", "William Jia", "Fusheng Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0095872.g002", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increased_anti_tumor_efficacy_of_VAE_compared_with_r_HSV_Endostar_and_PBS_/1079694", "title"=>"Increased anti-tumor efficacy of VAE compared with r-HSV, Endostar, and PBS.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-22 11:31:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/1560476"], "description"=>"<p>Mice with subcutaneous GSC-derived tumors were treated with a single dose (1×10<sup>7</sup> plaque-forming units) of rHSV, VAE, PBS, or Endostar 10 d after tumor cell implantation. (A) Representative pictures of immunohistochemical staining for CD31 in tumors isolated from mice 10 d after therapy with PBS, VAE, r-HSV, or Endostar. Scale bar: 10 µm. (B) The quantification of MVD in tumors treated with PBS, VAE, r-HSV, or Endostar. Data are shown as the mean MVD ± SEM for each group (n = 2 to 4 sections/tumor and n = 10 tumors/group). Note the significant difference in MVD for VAE versus r-HSV (*P<0.001), PBS versus VAE (**P<0.001), and Endostar versus VAE (***P<0.001).</p>", "links"=>[], "tags"=>["cell biology", "Cellular types", "Animal cells", "stem cells", "Molecular cell biology", "molecular biology", "Molecular biology techniques", "Gene therapy", "Infectious diseases", "Sexually transmitted diseases", "Herpes simplex", "neurology", "Neurological tumors", "Glioblastoma multiforme", "oncology", "Cancer treatment", "Antiangiogenesis therapy", "Cancers and neoplasms", "Model organisms", "Animal models", "Mouse models", "mvd", "perfusion", "animals", "treated", "vae", "compared"], "article_id"=>1079761, "categories"=>["Biological Sciences"], "users"=>["Guobin Zhang", "Guishan Jin", "Xiutao Nie", "Ruifang Mi", "Guidong Zhu", "William Jia", "Fusheng Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0095872.g003", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reduced_MVD_and_perfusion_in_animals_treated_with_VAE_compared_with_rHSV_Endostar_and_PBS_/1079761", "title"=>"Reduced MVD and perfusion in animals treated with VAE compared with rHSV, Endostar, and PBS.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-22 11:31:58"}

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