Species D Human Adenovirus Type 9 Exhibits Better Virus-Spread Ability for Antitumor Efficacy among Alternative Serotypes
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{"title"=>"Species D human adenovirus type 9 exhibits better virus-spread ability for antitumor efficacy among alternative serotypes", "type"=>"journal", "authors"=>[{"first_name"=>"Junji", "last_name"=>"Uchino", "scopus_author_id"=>"57198150436"}, {"first_name"=>"David T.", "last_name"=>"Curiel", "scopus_author_id"=>"22134188600"}, {"first_name"=>"Hideyo", "last_name"=>"Ugai", "scopus_author_id"=>"6603936630"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"372510353", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"84895103980", "issn"=>"19326203", "pmid"=>"24503714", "scopus"=>"2-s2.0-84895103980", "doi"=>"10.1371/journal.pone.0087342"}, "id"=>"f4ca766e-fedd-3802-8ff9-af8a3041e1a2", "abstract"=>"Species C human adenovirus serotype 5 (HAdV-C5) is widely used as a vector for cancer gene therapy, because it efficiently transduces target cells. A variety of HAdV-C5 vectors have been developed and tested in vitro and in vivo for cancer gene therapy. While clinical trials with HAdV-C5 vectors resulted in effective responses in many cancer patients, administration of HAdV-C5 vectors to solid tumors showed responses in a limited area. A biological barrier in tumor mass is considered to hinder viral spread of HAdV-C5 vectors from infected cells. Therefore, efficient virus-spread from an infected tumor cell to surrounding tumor cells is required for successful cancer gene therapy. In this study, we compared HAdV-C5 to sixteen other HAdV serotypes selected from species A to G for virus-spread ability in vitro. HAdV-D9 showed better virus-spread ability than other serotypes, and its viral progeny were efficiently released from infected cells during viral replication. Although the HAdV-D9 fiber protein contains a binding site for coxsackie B virus and adenovirus receptor (CAR), HAdV-D9 showed expanded tropism for infection due to human CAR (hCAR)-independent attachment to target cells. HAdV-D9 infection effectively killed hCAR-negative cancer cells as well as hCAR-positive cancer cells. These results suggest that HADV-D9, with its better virus-spread ability, could have improved therapeutic efficacy in solid tumors compared to HAdV-C5.", "link"=>"http://www.mendeley.com/research/species-d-human-adenovirus-type-9-exhibits-better-virusspread-ability-antitumor-efficacy-among-alter", "reader_count"=>10, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>3, "Student > Master"=>2, "Other"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>3, "Student > Master"=>2, "Other"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>2, "Psychology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Psychology"=>{"Psychology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}}, "reader_count_by_country"=>{"United Kingdom"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1375659"], "description"=>"a<p>Numbers refer to the serotypes of HAdVs.</p>b<p>Total PFU was calculated with the volume of purified HAdVs.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Gene therapy", "microbiology", "Vector biology", "Viral vectors", "Virology", "Viral classification", "DNA viruses", "Viral transmission and infection", "Clinical genetics", "oncology", "Cancer treatment", "titers", "hadvs"], "article_id"=>925735, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Junji Uchino", "David T. Curiel", "Hideyo Ugai"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087342.t001", "stats"=>{"downloads"=>3, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_biological_and_physical_titers_of_wild_type_HAdVs_used_in_this_study_/925735", "title"=>"Summary of biological and physical titers of wild type HAdVs used in this study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-02-04 03:47:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1375660"], "description"=>"a<p>Numbers refer to the serotypes of HAdVs.</p>b<p>Plaque sizes of HAdVs were represented as the average of the values obtained from ten individual single plaques.</p>c<p>Plaque sizes of these viruses were not able to be measured by a caliper.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Gene therapy", "microbiology", "Vector biology", "Viral vectors", "Virology", "Viral classification", "DNA viruses", "Viral transmission and infection", "Clinical genetics", "oncology", "Cancer treatment", "lines", "viral", "propagation", "plaque", "sizes"], "article_id"=>925736, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Junji Uchino", "David T. Curiel", "Hideyo Ugai"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087342.t002", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Host_cell_lines_used_for_viral_propagation_and_plaque_sizes_of_HAdVs_/925736", "title"=>"Host cell lines used for viral propagation and plaque sizes of HAdVs.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-02-04 03:47:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1375658"], "description"=>"<p>(A) Analysis of hCAR expression in various cancer cell lines by flow cytometry. Filled, gray histograms indicate stained cells; open, white histograms indicate unstained control cells. (B) Two-dimensional cell viability assay. Cancer cell lines were infected with HAdV-C5 (black squares) or HAdV-D9 (white squares) at indicated MOIs. Cell survival in each well was measured at 6 days post-infection using an MTS assay and plotted on y-axis as the percentage of the control values obtained from uninfected cells. (C) Three-dimensional cell viability assay. Spheroids were infected with HAdV-C5 (black squares) or HAdV-D9 (white squares) at indicated MOIs. Cell survival in each well was measured at 12 days post-infection using an MTT assay and plotted on y-axis as the percentage of the control values obtained from uninfected cells. Data points represent mean+standard error of the mean (n = 3).</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Gene therapy", "microbiology", "Vector biology", "Viral vectors", "Virology", "Viral classification", "DNA viruses", "Viral transmission and infection", "Clinical genetics", "oncology", "Cancer treatment", "hcar", "hadv-d9", "cancer"], "article_id"=>925734, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Junji Uchino", "David T. Curiel", "Hideyo Ugai"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087342.g004", "stats"=>{"downloads"=>4, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_hCAR_expression_and_cell_killing_activity_of_HAdV_D9_in_cancer_cell_lines_/925734", "title"=>"Analysis of hCAR expression and cell killing activity of HAdV-D9 in cancer cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-04 03:47:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1375652"], "description"=>"<p>A549 cells were infected with HAdV-C5 or HAdV-D9 at an MOI of 10 PFU/cell and harvested at various time points. Samples to measure the infectious titer of HAdVs were prepared from infected cells harvested along with culture medium (A), a fraction extracted from infected cells without culture medium (B), and culture medium (C). Infectious titers of HAdVs contained in each fraction were measured by triplicate TCID50 assays. Data points represent mean+standard error of the mean (n = 3). Unpaired student <i>t</i>-test analysis was performed with respect to HAdV-C5 at each time point and significance is indicated by *<i>P</i><0.05.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Gene therapy", "microbiology", "Vector biology", "Viral vectors", "Virology", "Viral classification", "DNA viruses", "Viral transmission and infection", "Clinical genetics", "oncology", "Cancer treatment", "hadv-d9", "infected", "cells"], "article_id"=>925731, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Junji Uchino", "David T. Curiel", "Hideyo Ugai"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087342.g002", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Release_of_HAdV_D9_from_infected_cells_to_culture_medium_/925731", "title"=>"Release of HAdV-D9 from infected cells to culture medium.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-04 03:47:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1375651"], "description"=>"<p>HAdVs (HAdV-C5, D9, D51, E4, and F41) were serially diluted with medium containing 2% FBS and A549 cells were infected with HAdV at the range of dilution of 5.0×10<sup>−8</sup> and 5.0×10<sup>−9</sup> for 1 hour. We performed plaque assay as described in the Materials and Methods section. At 14 days post-infection, we stained cells with 2 ml of medium containing 0.75% agar and 0.033% neutral red in order to visualize individual single plaques on A549 cells. Photographs of plaque morphology of HAdVs were taken with a digital camera.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Gene therapy", "microbiology", "Vector biology", "Viral vectors", "Virology", "Viral classification", "DNA viruses", "Viral transmission and infection", "Clinical genetics", "oncology", "Cancer treatment", "morphology", "hadvs", "a549"], "article_id"=>925730, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Junji Uchino", "David T. Curiel", "Hideyo Ugai"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087342.g001", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Plaque_morphology_of_HAdVs_on_A549_cells_/925730", "title"=>"Plaque morphology of HAdVs on A549 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-04 03:47:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1375676", "https://ndownloader.figshare.com/files/1375677", "https://ndownloader.figshare.com/files/1375678", "https://ndownloader.figshare.com/files/1375679", "https://ndownloader.figshare.com/files/1375680", "https://ndownloader.figshare.com/files/1375681"], "description"=>"<div><p>Species C human adenovirus serotype 5 (HAdV-C5) is widely used as a vector for cancer gene therapy, because it efficiently transduces target cells. A variety of HAdV-C5 vectors have been developed and tested <i>in vitro</i> and <i>in vivo</i> for cancer gene therapy. While clinical trials with HAdV-C5 vectors resulted in effective responses in many cancer patients, administration of HAdV-C5 vectors to solid tumors showed responses in a limited area. A biological barrier in tumor mass is considered to hinder viral spread of HAdV-C5 vectors from infected cells. Therefore, efficient virus-spread from an infected tumor cell to surrounding tumor cells is required for successful cancer gene therapy. In this study, we compared HAdV-C5 to sixteen other HAdV serotypes selected from species A to G for virus-spread ability <i>in vitro</i>. HAdV-D9 showed better virus-spread ability than other serotypes, and its viral progeny were efficiently released from infected cells during viral replication. Although the HAdV-D9 fiber protein contains a binding site for coxsackie B virus and adenovirus receptor (CAR), HAdV-D9 showed expanded tropism for infection due to human CAR (hCAR)-independent attachment to target cells. HAdV-D9 infection effectively killed hCAR-negative cancer cells as well as hCAR-positive cancer cells. These results suggest that HADV-D9, with its better virus-spread ability, could have improved therapeutic efficacy in solid tumors compared to HAdV-C5.</p></div>", "links"=>[], "tags"=>["genetics", "Human genetics", "Gene therapy", "microbiology", "Vector biology", "Viral vectors", "Virology", "Viral classification", "DNA viruses", "Viral transmission and infection", "Clinical genetics", "oncology", "Cancer treatment", "adenovirus", "exhibits", "virus-spread", "antitumor", "efficacy"], "article_id"=>925752, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Junji Uchino", "David T. Curiel", "Hideyo Ugai"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0087342.s001", "https://dx.doi.org/10.1371/journal.pone.0087342.s002", "https://dx.doi.org/10.1371/journal.pone.0087342.s003", "https://dx.doi.org/10.1371/journal.pone.0087342.s004", "https://dx.doi.org/10.1371/journal.pone.0087342.s005", "https://dx.doi.org/10.1371/journal.pone.0087342.s006"], "stats"=>{"downloads"=>5, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Species_D_Human_Adenovirus_Type_9_Exhibits_Better_Virus_Spread_Ability_for_Antitumor_Efficacy_among_Alternative_Serotypes_/925752", "title"=>"Species D Human Adenovirus Type 9 Exhibits Better Virus-Spread Ability for Antitumor Efficacy among Alternative Serotypes", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-02-04 03:47:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1375657"], "description"=>"<p>Cells (CHO and CHO-hCAR) were infected with HAdV-C5 or HAdV-D9 at an MOI of 100 genomes/cell, and total cell DNA extracted from infected cells were used for qPCR analysis. (A) Cellular uptakes of HAdVs in CHO and CHO-hCAR were represented as a fold of genome transfer in HAdV-C5-infected CHO cells at 1 hour post-infection and normalized by cellular uptake of HAdV-C5 in CHO cells; HAdV-C5 (black bars) and HAdV-D9 (white bars). (B and C) Cellular uptakes of HAdVs in a time-dependent manner in CHO (B) and CHO-hCAR (C). Total cell DNA was extracted from infected cells at 0, 30, and 60 min post-infection and used for qPCR analysis; HAdV-C5 (black squares) and HAdV-D9 (white squares). Data points represent mean+standard error of the mean (n = 3). CHO; human CAR negative CHO cells and CHO-hCAR; CHO cells stably expressing human CAR. (D) CHO-hCAR cells were treated with the HAdV-C5 fiber knob protein at a final concentration of 0, 0.5, 5.0 or 50 µg/ml at 4°C for 1 hour and then infected with HAdV at an MOI of 100 genomes/cell at 37°C for 1 hour. HAdV-C5 (black bars) and HAdV-D9 (white bars). (E) Cellular uptakes of HAdV-D9 in cancer cells which express little or no hCAR. Cells were infected with HAdV-C5 or HAdV-D9 at an MOI of 100 genomes/cell for 1 hour post-infection, and total cell DNA extracted from infected cells was analyzed by qPCR. HAdV-C5 (black bars) and HAdV-D9 (white bars). Cellular uptakes of HAdVs in cell lines were represented as (A) a fold of genome transfer, (B, C and D) a percentage of genome transfer, and (E) Genome copy numbers per 50 ng of total DNA of each HAdV. Data points represent mean+standard error of the mean (n = 3).</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Gene therapy", "microbiology", "Vector biology", "Viral vectors", "Virology", "Viral classification", "DNA viruses", "Viral transmission and infection", "Clinical genetics", "oncology", "Cancer treatment", "uptake", "hadv-d9", "independently"], "article_id"=>925733, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Junji Uchino", "David T. Curiel", "Hideyo Ugai"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087342.g003", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cellular_uptake_of_HAdV_D9_independently_of_human_CAR_/925733", "title"=>"Cellular uptake of HAdV-D9 independently of human CAR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-04 03:47:26"}

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  • {"unique-ip"=>"9", "full-text"=>"3", "pdf"=>"9", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
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Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[291]}, {"subject_area"=>"/Medicine and health sciences/Clinical genetics", "average_usage"=>[306, 468]}, {"subject_area"=>"/Physical sciences/Chemistry", "average_usage"=>[262]}]}
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