A Combretastatin-Mediated Decrease in Neutrophil Concentration in Peripheral Blood and the Impact on the Anti-Tumor Activity of This Drug in Two Different Murine Tumor Models
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{"title"=>"A combretastatin-mediated decrease in neutrophil concentration in peripheral blood and the impact on the anti-tumor activity of this drug in two different murine tumor models", "type"=>"journal", "authors"=>[{"first_name"=>"Anja Bille", "last_name"=>"Bohn", "scopus_author_id"=>"47761084200"}, {"first_name"=>"Thomas", "last_name"=>"Wittenborn", "scopus_author_id"=>"32467605900"}, {"first_name"=>"Anne Sofie", "last_name"=>"Brems-Eskildsen", "scopus_author_id"=>"24476079200"}, {"first_name"=>"Tinne", "last_name"=>"Laurberg", "scopus_author_id"=>"6507447829"}, {"first_name"=>"Lotte Bonde", "last_name"=>"Bertelsen", "scopus_author_id"=>"36150364000"}, {"first_name"=>"Thomas", "last_name"=>"Nielsen", "scopus_author_id"=>"55702887800"}, {"first_name"=>"Hans", "last_name"=>"Stødkilde-Jørgensen", "scopus_author_id"=>"34975952700"}, {"first_name"=>"Bjarne Kuno", "last_name"=>"Møller", "scopus_author_id"=>"7202709862"}, {"first_name"=>"Michael R.", "last_name"=>"Horsman", "scopus_author_id"=>"7005349962"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84907856513", "pmid"=>"25299269", "sgr"=>"84907856513", "doi"=>"10.1371/journal.pone.0110091", "issn"=>"19326203", "pui"=>"600116369"}, "id"=>"4ec16b20-7272-3b16-b658-1b1333b222b4", "abstract"=>"The vascular disrupting agent combretastatin A-4 disodium phosphate (CA4P) induces fluctuations in peripheral blood neutrophil concentration. Because neutrophils have the potential to induce both vascular damage and angiogenesis we analyzed neutrophil involvement in the anti-tumoral effects of CA4P in C3H mammary carcinomas in CDF1 mice and in SCCVII squamous cell carcinomas in C3H/HeN mice. Flow cytometry analyses of peripheral blood before and up to 144 h after CA4P administration (25 and 250 mg/kg) revealed a decrease 1 h after treatment, followed by an early (3-6 h) and a late (>72 h) increase in the granulocyte concentration. We suggest that the early increase (3-6 h) in granulocyte concentration was caused by the initial decrease at 1 h and found that the late increase was associated with tumor size, and hence independent of CA4P. No alterations in neutrophil infiltration into the C3H tumor after CA4P treatment (25 and 250 mg/kg) were found. Correspondingly, neutrophil depletion in vivo, using an anti-neutrophil antibody, followed by CA4P treatment (25 mg/kg) did not increase the necrotic fraction in C3H tumors significantly. However, by increasing the CA4P dose to 250 mg/kg we found a significant increase of 359% in necrotic fraction when compared to neutrophil-depleted mice; in mice with no neutrophil depletion CA4P induced an 89% change indicating that the presence of neutrophils reduced the effect of CA4P. In contrast, neither CA4P nor 1A8 affected the necrotic fraction in the SCCVII tumors significantly. Hence, we suggest that the initial decrease in granulocyte concentration was caused by non-tumor-specific recruitment of neutrophils and that neutrophils may attenuate CA4P-mediated anti-tumor effect in some tumor models.", "link"=>"http://www.mendeley.com/research/combretastatinmediated-decrease-neutrophil-concentration-peripheral-blood-impact-antitumor-activity", "reader_count"=>5, "reader_count_by_academic_status"=>{"Researcher"=>1, "Student > Ph. D. Student"=>2, "Student > Master"=>1, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Researcher"=>1, "Student > Ph. D. Student"=>2, "Student > Master"=>1, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>1, "Medicine and Dentistry"=>1, "Veterinary Science and Veterinary Medicine"=>1, "Unspecified"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Spain"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1711829"], "description"=>"<p>A) and C) Granulocytes/ml peripheral blood as a function of hours after treatment with 25 mg/kg (• ○) or 250 mg/kg (▪ □) CA4P in C3H mammary carcinoma bearing (• ▪) and non-tumor bearing (○ □) CDF1 mice (n = 5–15). Blood samples from the saline-treated groups are depicted in the graphs at t = 0 h. In A) ▴ shows the granulocyte concentration in tumor bearing mice 1 h (depicted at t = 0) and 144 h after a saline injection (n = 15). Kruskal-Wallis One Way Analysis of Variance on Ranks was used to analyze for changes over time within each CA4P dose compared to t = 0 in each group. C) is a close up of the first 24 hours after treatment (shown in A). B) Granulocyte concentration as a function of tumor volume in CDF1 mice (n = 14). Pearson’s correlation coefficient = 0.88, p<0.001. D) Granulocytes/ml peripheral blood 1 h after treatment with PBS or 25 mg/kg CA4P in SCCVII squamous cell carcinoma bearing C3H/HeN mice (n = 10, Student’s t-test p<0.001). Data is presented as median values and the 25<sup>th</sup> and 75<sup>th</sup> percentiles (error bars) in A) and C), as single values in B), and as mean ± SEM in D).</p>", "links"=>[], "tags"=>["Different Murine Tumor Models", "flow cytometry analyses", "sccvii", "C 3H mice", "neutrophils", "C 3H tumor", "C 3H tumors", "CA 4P", "granulocyte concentration", "CDF 1 mice", "CA 4P dose", "mg", "blood neutrophil concentration", "decrease 1 h", "neutrophil depletion CA 4P"], "article_id"=>1199411, "categories"=>["Biological Sciences"], "users"=>["Anja Bille Bohn", "Thomas Wittenborn", "Anne Sofie Brems-Eskildsen", "Tinne Laurberg", "Lotte Bonde Bertelsen", "Thomas Nielsen", "Hans Stødkilde-Jørgensen", "Bjarne Kuno Møller", "Michael R. Horsman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0110091.g001", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Granulocyte_concentration_in_peripheral_blood_after_CA4P_treatment_/1199411", "title"=>"Granulocyte concentration in peripheral blood after CA4P treatment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-09 03:40:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1711839"], "description"=>"<p>A) <i>In vitro</i> effect of 2 h incubation of whole blood in the presence of CA4P (10 µM), CA4 (10 µM), DMSO diluted in saline, or saline on the percentage of apoptotic or dead granulocytes. Data is presented as mean + SEM (n = 3). B) A representative forward-side scatter demonstrating gating of the granulocytes (the pink oval gate). C) Verification of Gr-1 positivity of cells in the granulocyte gate. The red line shows the isotype control and the blue line represents the granulocytes. D–H) Annexin V (expressed by apoptotic cells) and 7AAD (expressed by dead cells) expression in granulocytes from D) a negative control (no 7AAD or annexin V staining), or after incubation with E) saline, F) DMSO, G) CA4, or H) CA4P.</p>", "links"=>[], "tags"=>["Different Murine Tumor Models", "flow cytometry analyses", "sccvii", "C 3H mice", "neutrophils", "C 3H tumor", "C 3H tumors", "CA 4P", "granulocyte concentration", "CDF 1 mice", "CA 4P dose", "mg", "blood neutrophil concentration", "decrease 1 h", "neutrophil depletion CA 4P"], "article_id"=>1199413, "categories"=>["Biological Sciences"], "users"=>["Anja Bille Bohn", "Thomas Wittenborn", "Anne Sofie Brems-Eskildsen", "Tinne Laurberg", "Lotte Bonde Bertelsen", "Thomas Nielsen", "Hans Stødkilde-Jørgensen", "Bjarne Kuno Møller", "Michael R. Horsman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0110091.g002", "stats"=>{"downloads"=>0, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vitro_CA4P_toxicity_assay_/1199413", "title"=>"In vitro CA4P toxicity assay.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-09 03:40:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1711840"], "description"=>"<p>A) The estimated area fraction of myeloperoxidase positive granulocytes in tumor tissue from C3H mammary carcinoma bearing CDF1 mice treated with 25 mg/kg CA4P for 1, 3, 6, or 24 hours, with 250 mg/kg CA4P for 24 hours, or in mice injected with saline. B) Representative tumor tissue sections from mice injected with saline and mice treated with 25 mg/kg CA4P (3 hours post-injection). The sections have been stained with anti-myeloperoxidase antibody before estimation. Data is presented as mean + SEM (n = 4–9).</p>", "links"=>[], "tags"=>["Different Murine Tumor Models", "flow cytometry analyses", "sccvii", "C 3H mice", "neutrophils", "C 3H tumor", "C 3H tumors", "CA 4P", "granulocyte concentration", "CDF 1 mice", "CA 4P dose", "mg", "blood neutrophil concentration", "decrease 1 h", "neutrophil depletion CA 4P"], "article_id"=>1199414, "categories"=>["Biological Sciences"], "users"=>["Anja Bille Bohn", "Thomas Wittenborn", "Anne Sofie Brems-Eskildsen", "Tinne Laurberg", "Lotte Bonde Bertelsen", "Thomas Nielsen", "Hans Stødkilde-Jørgensen", "Bjarne Kuno Møller", "Michael R. Horsman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0110091.g003", "stats"=>{"downloads"=>1, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Estimated_area_fraction_of_myeloperoxidase_positive_granulocytes_in_tumor_tissue_/1199414", "title"=>"Estimated area fraction of myeloperoxidase positive granulocytes in tumor tissue.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-09 03:40:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1711842"], "description"=>"<p>A) VEGF, B) MIP-1α (CCL3), C) KC (CXCL1), and D) MIP-2 (CXCL2) concentration in tumors as a function of hours after treatment with 25 mg/kg CA4P and in tumors from saline-treated mice. A) and C) Data is presented as mean ± SEM. B) and D) Data is presented as the median (horizontal bar), the 25<sup>th</sup> and 75<sup>th</sup> percentile (bottom and top of boxes) and the 10<sup>th</sup> and 90<sup>th</sup> percentiles (error bars). For all data n = 10.</p>", "links"=>[], "tags"=>["Different Murine Tumor Models", "flow cytometry analyses", "sccvii", "C 3H mice", "neutrophils", "C 3H tumor", "C 3H tumors", "CA 4P", "granulocyte concentration", "CDF 1 mice", "CA 4P dose", "mg", "blood neutrophil concentration", "decrease 1 h", "neutrophil depletion CA 4P"], "article_id"=>1199416, "categories"=>["Biological Sciences"], "users"=>["Anja Bille Bohn", "Thomas Wittenborn", "Anne Sofie Brems-Eskildsen", "Tinne Laurberg", "Lotte Bonde Bertelsen", "Thomas Nielsen", "Hans Stødkilde-Jørgensen", "Bjarne Kuno Møller", "Michael R. Horsman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0110091.g004", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effect_of_CA4P_treatment_on_cytokine_levels_in_C3H_mammary_carcinomas_in_CDF1_mice_/1199416", "title"=>"The effect of CA4P treatment on cytokine levels in C3H mammary carcinomas in CDF1 mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-09 03:40:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1711843"], "description"=>"<p>A) Granulocytes (percentage of leucocytes) in non-tumor bearing CDF1 mice as a function of hours after treatment (n = 5). The mice were treated with PBS (○), the anti-neutrophil antibody 1A8 (•), CA4P (25 mg/kg, ▿), 1A8 and CA4P (25 mg/kg) in combination (▴), CA4P (250 mg/kg, □), or 1A8 and CA4P (250 mg/kg) in combination (▪). B) Granulocytes as a percentage of leucocytes in C3H/HeN mice 24 h after injection of PBS, 1A8, CA4P (25 mg/kg), or 1A8 and CA4P in combination (n = 5). The data is presented as median values and error bars represent the 25<sup>th</sup> and 75<sup>th</sup> percentiles.</p>", "links"=>[], "tags"=>["Different Murine Tumor Models", "flow cytometry analyses", "sccvii", "C 3H mice", "neutrophils", "C 3H tumor", "C 3H tumors", "CA 4P", "granulocyte concentration", "CDF 1 mice", "CA 4P dose", "mg", "blood neutrophil concentration", "decrease 1 h", "neutrophil depletion CA 4P"], "article_id"=>1199417, "categories"=>["Biological Sciences"], "users"=>["Anja Bille Bohn", "Thomas Wittenborn", "Anne Sofie Brems-Eskildsen", "Tinne Laurberg", "Lotte Bonde Bertelsen", "Thomas Nielsen", "Hans Stødkilde-Jørgensen", "Bjarne Kuno Møller", "Michael R. Horsman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0110091.g005", "stats"=>{"downloads"=>1, "page_views"=>28, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Verification_of_neutrophil_depletion_in_CDF1_and_C3H_HeN_mice_/1199417", "title"=>"Verification of neutrophil-depletion in CDF1 and C3H/HeN mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-09 03:40:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1711845"], "description"=>"<p>1A8: anti-neutrophil antibody, CA4P: Combretastatin A-4 disodium phosphate.</p><p>*signifcantly different from the control group,</p><p>*′significantly different from the 1A8 group. Values are mean ± SEM (n = 5–21).</p><p>Effect of neutrophil depletion on CA4P-mediated necrosis.</p>", "links"=>[], "tags"=>["Different Murine Tumor Models", "flow cytometry analyses", "sccvii", "C 3H mice", "neutrophils", "C 3H tumor", "C 3H tumors", "CA 4P", "granulocyte concentration", "CDF 1 mice", "CA 4P dose", "mg", "blood neutrophil concentration", "decrease 1 h", "neutrophil depletion CA 4P"], "article_id"=>1199419, "categories"=>["Biological Sciences"], "users"=>["Anja Bille Bohn", "Thomas Wittenborn", "Anne Sofie Brems-Eskildsen", "Tinne Laurberg", "Lotte Bonde Bertelsen", "Thomas Nielsen", "Hans Stødkilde-Jørgensen", "Bjarne Kuno Møller", "Michael R. Horsman"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0110091.t001", "stats"=>{"downloads"=>6, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_neutrophil_depletion_on_CA4P_mediated_necrosis_/1199419", "title"=>"Effect of neutrophil depletion on CA4P-mediated necrosis.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-10-09 03:40:53"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"3", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
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  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"2", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"13", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"2", "full-text"=>"1", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
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  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
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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"=>"/Biology and life sciences/Anatomy", "average_usage"=>[267]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[286]}, {"subject_area"=>"/Biology and life sciences/Immunology", "average_usage"=>[293]}, {"subject_area"=>"/Medicine and health sciences/Hematology", "average_usage"=>[256]}, {"subject_area"=>"/Medicine and health sciences/Immunology", "average_usage"=>[289]}]}
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