Improved Local and Systemic Anti-Tumor Efficacy for Irreversible Electroporation in Immunocompetent versus Immunodeficient Mice
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{"title"=>"Improved Local and Systemic Anti-Tumor Efficacy for Irreversible Electroporation in Immunocompetent versus Immunodeficient Mice", "type"=>"journal", "authors"=>[{"first_name"=>"Robert E.", "last_name"=>"Neal", "scopus_author_id"=>"34873115100"}, {"first_name"=>"John H.", "last_name"=>"Rossmeisl", "scopus_author_id"=>"6603826124"}, {"first_name"=>"John L.", "last_name"=>"Robertson", "scopus_author_id"=>"7404532496"}, {"first_name"=>"Christopher B.", "last_name"=>"Arena", "scopus_author_id"=>"35774004300"}, {"first_name"=>"Erica M.", "last_name"=>"Davis", "scopus_author_id"=>"36672720600"}, {"first_name"=>"Ravi N.", "last_name"=>"Singh", "scopus_author_id"=>"55613230511"}, {"first_name"=>"Jonathan", "last_name"=>"Stallings", "scopus_author_id"=>"55454182000"}, {"first_name"=>"Rafael V.", "last_name"=>"Davalos", "scopus_author_id"=>"6701641687"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23717630", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0064559", "issn"=>"19326203", "scopus"=>"2-s2.0-84878147451", "pui"=>"368982586", "sgr"=>"84878147451"}, "id"=>"cf8c2693-2f78-3d8d-ad7b-f90562e95b08", "abstract"=>"<p>Irreversible electroporation (IRE) is a non-thermal focal ablation technique that uses a series of brief but intense electric pulses delivered into a targeted region of tissue, killing the cells by irrecoverably disrupting cellular membrane integrity. This study investigates if there is an improved local anti-tumor response in immunocompetent (IC) BALB/c versus immunodeficient (ID) nude mice, including the potential for a systemic protective effect against rechallenge. Subcutaneous murine renal carcinoma tumors were treated with an IRE pulsing protocol that used 60% of the predicted voltage required to invoke complete regressions in the ID mice. Tumors were followed for 34 days following treatment for 11 treated mice from each strain, and 7 controls from each strain. Mouse survival based on tumor burden and the progression-free disease period was substantially longer in the treated IC mice relative to the treated ID mice and sham controls for both strains. Treated IC mice were rechallenged with the same cell line 18 days after treatment, where growth of the second tumors was shown to be significantly reduced or prevented entirely. There was robust CD3<sup>+</sup> cell infiltration in some treated BALB/C mice, with immunocytes focused at the transition between viable and dead tumor. There was no difference in the low immunocyte presence for untreated tumors, nude mice, and matrigel-only injections in both strains. These findings suggest IRE therapy may have greater therapeutic efficacy in immunocompetent patients than what has been suggested by immunodeficient models, and that IRE may invoke a systemic response beyond the targeted ablation region.</p>", "link"=>"http://www.mendeley.com/research/improved-local-systemic-antitumor-efficacy-irreversible-electroporation-immunocompetent-versus-immun", "reader_count"=>28, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>7, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>9, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>7, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>9, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>9, "Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>1, "Medicine and Dentistry"=>9, "Business, Management and Accounting"=>1, "Physics and Astronomy"=>2, "Chemical Engineering"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>9}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Physics and Astronomy"=>{"Physics and Astronomy"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>2}, "Chemical Engineering"=>{"Chemical Engineering"=>1}}, "reader_count_by_country"=>{"United States"=>1, "Brazil"=>1, "India"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1559607"], "description"=>"<p>Plate electrodes are placed on either side of the subcutaneous murine tumor, with a highly conductive gel facilitating improved current delivery into the tumor. Two small electrodes are inserted directly into the tumor perpendicular to the plate electrodes to measure the voltage drop between them, ensuring adequate electric field distribution through the center of the tumor. Treated groups had IRE electric pulses delivered through the plate electrodes, while controls had no pulse delivery.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Immune system proteins", "immunology", "immunity", "Adaptive immunity", "Immune activation", "Innate immunity", "Antigen processing and recognition", "Immune response", "Bioengineering", "Biomedical Engineering", "Medical devices", "Clinical immunology", "oncology", "Cancer treatment", "immunotherapy"], "article_id"=>1078937, "categories"=>["Biological Sciences", "Medicine", "Engineering"], "users"=>["Robert E. Neal II", "John H. Rossmeisl Jr", "John L. Robertson", "Christopher B. Arena", "Erica M. Davis", "Ravi N. Singh", "Jonathan Stallings", "Rafael V. Davalos"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0064559.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_of_experimental_setup_/1078937", "title"=>"Schematic of experimental setup.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-24 11:22:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1559612"], "description"=>"<p>Survival of the different experimental groups based on euthanasia timepoints resulting from excessive tumor burden, when tumors reached 18 mm in any given dimension. The total experimental period was 34 days post-IRE treatment. Where 70% of the treated immunocompetent (IC) BALB/c mice survived until the endpoint of the study, nearly all control IC mice and both experimental immunodeficient (ID) nude mice groups were euthanized prior to reaching the endpoint due to excessive tumor burden.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Immune system proteins", "immunology", "immunity", "Adaptive immunity", "Immune activation", "Innate immunity", "Antigen processing and recognition", "Immune response", "Bioengineering", "Biomedical Engineering", "Medical devices", "Clinical immunology", "oncology", "Cancer treatment", "immunotherapy"], "article_id"=>1078943, "categories"=>["Biological Sciences", "Medicine", "Engineering"], "users"=>["Robert E. Neal II", "John H. Rossmeisl Jr", "John L. Robertson", "Christopher B. Arena", "Erica M. Davis", "Ravi N. Singh", "Jonathan Stallings", "Rafael V. Davalos"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0064559.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kaplan_Meier_survival_plot_/1078943", "title"=>"Kaplan-Meier survival plot.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-24 11:22:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1559624"], "description"=>"<p>(A) Imputed median primary tumor volumes (mm<sup>3</sup>) for each group, showing significantly smaller median tumor size in the treated immunocompetent (IC) BALB/c mice. (B–E) Individual trial tumor comparisons between (B,D) immunodeficient (ID) nude and (C,E) immunocompetent mouse strains for (B,C) sham and (D,E) pulsed treatment groups, showing a clear improvement in progressive disease free survival for the treated IC mice (E) relative to both controls and treated ID mice (B–D). Treated ID mice show an initial pause in tumor volume for the first 12 days from the treatment, followed by progressive growth, a result of selecting a sub-optimal IRE pulsing protocol for this study. All endpoints in data are a result of euthanasia due to tumor reaching 18 mm in any dimension.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Immune system proteins", "immunology", "immunity", "Adaptive immunity", "Immune activation", "Innate immunity", "Antigen processing and recognition", "Immune response", "Bioengineering", "Biomedical Engineering", "Medical devices", "Clinical immunology", "oncology", "Cancer treatment", "immunotherapy", "inoculation"], "article_id"=>1078955, "categories"=>["Biological Sciences", "Medicine", "Engineering"], "users"=>["Robert E. Neal II", "John H. Rossmeisl Jr", "John L. Robertson", "Christopher B. Arena", "Erica M. Davis", "Ravi N. Singh", "Jonathan Stallings", "Rafael V. Davalos"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0064559.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Original_inoculation_tumor_volume_curves_/1078955", "title"=>"Original inoculation tumor volume curves.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-24 11:22:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1559630"], "description"=>"<p>Mean tumor volume for all surviving mice at days 10, 15, 20, and 25 post-treatment. Mann-Whitney statistical significance was calculated between immunodeficient (ID) nude mice and immunocompetent (IC) mice that received treatment or sham control, showing statistically significant difference in mean tumor size for the groups at different timepoints, where treated ID mice show a difference at days 10 and 15, while treated IC mice show a significant difference for all time points considered. *0.05>p>0.01; **0.01>p>0.001; ***p<0.001.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Immune system proteins", "immunology", "immunity", "Adaptive immunity", "Immune activation", "Innate immunity", "Antigen processing and recognition", "Immune response", "Bioengineering", "Biomedical Engineering", "Medical devices", "Clinical immunology", "oncology", "Cancer treatment", "immunotherapy", "means"], "article_id"=>1078961, "categories"=>["Biological Sciences", "Medicine", "Engineering"], "users"=>["Robert E. Neal II", "John H. Rossmeisl Jr", "John L. Robertson", "Christopher B. Arena", "Erica M. Davis", "Ravi N. Singh", "Jonathan Stallings", "Rafael V. Davalos"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0064559.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Primary_tumor_volume_means_and_standard_deviations_/1078961", "title"=>"Primary tumor volume means and standard deviations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-24 11:22:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1559635"], "description"=>"<p>Growth curves for immunocompetent BALB/c mice for tumors grown after the (A) first inoculation and (B) rechallenge inoculation, which occurred 18 days after treatment of the first tumor. Average time for first inoculation tumors to reach minimum protocol treatment size of approximately 5×5 mm across and 4 mm deep was 9.7 days. Rechallenge inoculation tumors showed significantly delayed or completely inhibited growth of contralateral rechallenge tumors from the second inoculation.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Immune system proteins", "immunology", "immunity", "Adaptive immunity", "Immune activation", "Innate immunity", "Antigen processing and recognition", "Immune response", "Bioengineering", "Biomedical Engineering", "Medical devices", "Clinical immunology", "oncology", "Cancer treatment", "immunotherapy", "rechallenge"], "article_id"=>1078966, "categories"=>["Biological Sciences", "Medicine", "Engineering"], "users"=>["Robert E. Neal II", "John H. Rossmeisl Jr", "John L. Robertson", "Christopher B. Arena", "Erica M. Davis", "Ravi N. Singh", "Jonathan Stallings", "Rafael V. Davalos"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0064559.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Primary_and_rechallenge_BALB_c_tumor_growth_curves_/1078966", "title"=>"Primary and rechallenge BALB/c tumor growth curves.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-24 11:22:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1559650"], "description"=>"<p>Histology of different inoculation conditions for (A–D) immunodeficient (ID) Nude mice and (E–H) immunocompetent (IC) BALB/C mice. (A,E) untreated initial tumors, (B,F) matrigel controls, (C,G), treated initial tumors (T1), and (D,H) untreated rechallenge tumors (T2). There is little overall immune reaction present in (A,B,E,F), the untreated T1 tumors and untreated matrigel controls, with no appreciable immunocyte presence difference between ID and IC groups. ID treated T1 (C) and untreated T2 (D) tumors had a relatively low immune response, with some neutrophils present. Arrows in (C,G) denote transition between dead and viable tumor cells in both group treated T1s. Treated IC T1 tumors (G) had most immune reaction at the transition zone between dead and viable tumor. Untreated T2 rechallenge tumors in the IC mice (H) show the presence of lymphocytes (arrowheads) and polymorphonuclear leukocytes (arrows). All scale bars 200 µm. Panels (A,B,C,E,F,G) 200x and (D, H) 400x magnification.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Immune system proteins", "immunology", "immunity", "Adaptive immunity", "Immune activation", "Innate immunity", "Antigen processing and recognition", "Immune response", "Bioengineering", "Biomedical Engineering", "Medical devices", "Clinical immunology", "oncology", "Cancer treatment", "immunotherapy", "eosin", "staining"], "article_id"=>1078981, "categories"=>["Biological Sciences", "Medicine", "Engineering"], "users"=>["Robert E. Neal II", "John H. Rossmeisl Jr", "John L. Robertson", "Christopher B. Arena", "Erica M. Davis", "Ravi N. Singh", "Jonathan Stallings", "Rafael V. Davalos"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0064559.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Haematoxylin_and_Eosin_staining_of_various_treatment_groups_/1078981", "title"=>"Haematoxylin and Eosin staining of various treatment groups.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-24 11:22:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1559679"], "description"=>"<p>CD3<sup>+</sup> staining, indicative for T-cell presence, performed for (A,C) untreated and (B,D) treated initial T1 tumors between (A,B) ID nude and (C,D) IC BALB/c mice. There is no notable difference observed in CD3<sup>+</sup> infiltration for ID nude mice between (A) untreated and (B) treated tumors. For the IC BALB/c mice, a robust increase in CD3<sup>+</sup> (T-cell) infiltration is observed in some treated tumors (D) relative to untreated T1 controls (C). Increased T-cell presence in treated T1 IC mice was also more robust than for both groups for nude mice (A,B). All scale bars 200 µm. Panels (A,C,D) 200x, panel (B) 400x magnification.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Immune system proteins", "immunology", "immunity", "Adaptive immunity", "Immune activation", "Innate immunity", "Antigen processing and recognition", "Immune response", "Bioengineering", "Biomedical Engineering", "Medical devices", "Clinical immunology", "oncology", "Cancer treatment", "immunotherapy", "immunohistochemsistry"], "article_id"=>1079010, "categories"=>["Biological Sciences", "Medicine", "Engineering"], "users"=>["Robert E. Neal II", "John H. Rossmeisl Jr", "John L. Robertson", "Christopher B. Arena", "Erica M. Davis", "Ravi N. Singh", "Jonathan Stallings", "Rafael V. Davalos"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0064559.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CD3_Immunohistochemsistry_of_primary_T1_tumors_/1079010", "title"=>"CD3<sup>+</sup> Immunohistochemsistry of primary (T1) tumors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-24 11:22:14"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"5", "full-text"=>"3", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"20", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"10", "full-text"=>"12", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"5", "full-text"=>"9", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"7", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"6", "full-text"=>"4", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"8", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"6", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[269, 466, 588, 697, 800, 896, 988, 1076, 1165, 1254, 1340, 1417]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[272, 472, 600, 713, 815, 911, 1004, 1094, 1185, 1273, 1358, 1441]}, {"subject_area"=>"/Biology and life sciences/Immunology", "average_usage"=>[266, 466, 591, 701, 799, 887, 982, 1067, 1155, 1237, 1317, 1395, 1458]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[264, 460, 584, 692, 794, 887, 978, 1067, 1154, 1241, 1328, 1408, 1474]}, {"subject_area"=>"/Medicine and health sciences/Anatomy and physiology", "average_usage"=>[253, 430]}, {"subject_area"=>"/Medicine and health sciences/Public and occupational health", "average_usage"=>[291, 491, 610, 723, 817, 906, 991, 1071, 1153, 1238, 1324, 1411, 1478]}]}
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