Neutralization of IL-8 Prevents the Induction of Dermatologic Adverse Events Associated with the Inhibition of Epidermal Growth Factor Receptor
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{"title"=>"Neutralization of IL-8 prevents the induction of dermatologic adverse events associated with the inhibition of epidermal growth factor receptor", "type"=>"journal", "authors"=>[{"first_name"=>"Nannie", "last_name"=>"Bangsgaard", "scopus_author_id"=>"6507163155"}, {"first_name"=>"Mischa", "last_name"=>"Houtkamp", "scopus_author_id"=>"7801541909"}, {"first_name"=>"Danita H.", "last_name"=>"Schuurhuis", "scopus_author_id"=>"6603416154"}, {"first_name"=>"Paul W H I", "last_name"=>"Parren", "scopus_author_id"=>"7004044140"}, {"first_name"=>"Ole", "last_name"=>"Baadsgaard", "scopus_author_id"=>"7005928695"}, {"first_name"=>"Hans W M", "last_name"=>"Niessen", "scopus_author_id"=>"7004569598"}, {"first_name"=>"Lone", "last_name"=>"Skov", "scopus_author_id"=>"7005922600"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84862648351", "pui"=>"365082990", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0039706", "issn"=>"19326203", "scopus"=>"2-s2.0-84862648351", "pmid"=>"22761877"}, "id"=>"07e485d9-36d4-30fd-850d-f6b205d3766d", "abstract"=>"Epidermal growth factor receptor (EGFR) inhibitors are widely used in the treatment of cancer. EGFR-targeted treatment is known to be associated with a high incidence of dermatological adverse reactions, including papulopustular rash, which can be dose-limiting and may affect compliance to treatment. Currently, the pathways involved in EGFR inhibitor-induced rash are poorly understood and few treatment options for this adverse event are available. Here, we developed a model for induction of papulopustular rash in healthy human volunteers by subcutaneous injection of the anti-EGFR monoclonal antibody zalutumumab. The injection sites and surrounding skin were evaluated by a dermatologist for the presence or absence of papulopustular rash and skin biopsies were taken to confirm the macroscopical findings by immunohistochemistry. Locally injected zalutumumab induced a papulopustular rash, characterized by acute follicular neutrophil-rich hair follicle inflammation, and thus mimicked adverse events induced by systemic administration of EGFR inhibitors. In this model, we tested the hypothesis that neutrophils, attracted by IL-8, play a central role in the observed rash. Indeed, concomitant local repeat dose treatment with HuMab-10F8, a neutralizing human antibody against IL-8, reduced the rash. Inhibition of IL-8 can therefore ameliorate dermatological adverse events induced by treatment with EGFR inhibitors.", "link"=>"http://www.mendeley.com/research/neutralization-il8-prevents-induction-dermatologic-adverse-events-associated-inhibition-epidermal-gr", "reader_count"=>17, "reader_count_by_academic_status"=>{"Researcher"=>5, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>3, "Other"=>3, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>5, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>3, "Other"=>3, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>5, "Design"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>2}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>1, "Italy"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/619233"], "description"=>"<p>Injection sites of a patient from study part III is shown. Injection of 100 μg zalutumumab alone (E) induced pustules following two injections. Injection of zalutumumab combined with HuMab-10F8, followed by four daily HuMab-10F8 injections (C), suppressed the induction of pustules. The saline control is also shown (N).</p>", "links"=>[], "tags"=>["humab-10f8", "zalutumumab-induced"], "article_id"=>289723, "categories"=>["Cancer", "Developmental Biology", "Pharmacology", "Immunology"], "users"=>["Nannie Bangsgaard", "Mischa Houtkamp", "Danita H. Schuurhuis", "Paul W. H. I. Parren", "Ole Baadsgaard", "Hans W. M. Niessen", "Lone Skov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039706.g004", "stats"=>{"downloads"=>1, "page_views"=>37, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_HuMab_10F8_on_zalutumumab_induced_pustules_/289723", "title"=>"Effect of HuMab-10F8 on zalutumumab-induced pustules.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 03:27:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/619014"], "description"=>"<p>Representative sections are shown of skin biopsies of one subject for part I of the study (following two injections of 10 μg of zalutumumab). Sections were stained with HE to show nucleated cells and (patho-)histological features. In the saline-injected skin (A, C), inflammatory cells were virtually absent and the hair follicle structure was intact. Note that after zalutumumab injection (B, D), the hair follicle structure was destroyed and extensive influx of inflammatory cells (including neutrophils) in the vicinity of the destroyed hair follicle/glandular structures can be observed (asterisks). Scale bars are 100 µm (A, B) and 20 µm (C, D).</p>", "links"=>[], "tags"=>["biopsies", "saline-", "zalutumumab-injected"], "article_id"=>289506, "categories"=>["Cancer", "Developmental Biology", "Pharmacology", "Immunology"], "users"=>["Nannie Bangsgaard", "Mischa Houtkamp", "Danita H. Schuurhuis", "Paul W. H. I. Parren", "Ole Baadsgaard", "Hans W. M. Niessen", "Lone Skov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039706.g002", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histology_of_biopsies_from_saline_or_zalutumumab_injected_skin_part_I_of_the_study_/289506", "title"=>"Histology of biopsies from saline- or zalutumumab-injected skin (part I of the study).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 03:26:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/619456"], "description"=>"<p>Every injection of zalutumumab was accompanied by a control injection of an identical volume of isotonic saline at a different site. In the third part the dose escalation started at 100 μg.</p>", "links"=>[], "tags"=>["escalation", "zalutumumab"], "article_id"=>289944, "categories"=>["Cancer", "Developmental Biology", "Pharmacology", "Immunology"], "users"=>["Nannie Bangsgaard", "Mischa Houtkamp", "Danita H. Schuurhuis", "Paul W. H. I. Parren", "Ole Baadsgaard", "Hans W. M. Niessen", "Lone Skov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039706.t001", "stats"=>{"downloads"=>12, "page_views"=>86, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dose_escalation_schedule_for_zalutumumab_injections_/289944", "title"=>"Dose escalation schedule for zalutumumab injections.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 03:29:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/619155"], "description"=>"<p>The rash observed at the injection site of one subject in part II of the study, following two injections of 100 µg of zalutumumab each, is shown.</p>", "links"=>[], "tags"=>["rash", "was", "induced", "injection"], "article_id"=>289646, "categories"=>["Cancer", "Developmental Biology", "Pharmacology", "Immunology"], "users"=>["Nannie Bangsgaard", "Mischa Houtkamp", "Danita H. Schuurhuis", "Paul W. H. I. Parren", "Ole Baadsgaard", "Hans W. M. Niessen", "Lone Skov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039706.g003", "stats"=>{"downloads"=>2, "page_views"=>40, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Papulopustular_rash_was_induced_by_local_injection_of_zalutumumab_/289646", "title"=>"Papulopustular rash was induced by local injection of zalutumumab.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 03:27:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/619324"], "description"=>"<p>Data shown are representative sections of skin biopsies of one subject for part III of the study. Biopsies were taken at day 14 after two injections with 100 µg of zalutumumab with [A, C, E, G, I, K] or without HuMab-10F8 [B, D, F, H, J, L]. A, B: HE staining; C, D: staining for EGFR; E–H: staining for macrophages and I–L: staining for neutrophils. Extensive influx of inflammatory cells in the vicinity of the hair follicle with histological signs of folliculitis was observed in zalutumumab-injected skin (right panels), whereas in the zalutumumab-injected skin treated with HuMab-10F8 (left panels) inflammatory cells were virtually absent and sebaceous glands and hair follicles showed normal histological features. Inflammatory infiltrate in the zalutumumab-injected skin was mainly composed of neutrophils (neutrophil elastase positive cells, J, L) and to a lesser extent of macrophages; (CD68 positive cells F, H). Scale bars are 100 µm (A–F, I, J) and 20 µm (G, H, K, L). G, H, K and L are magnifications of the squared areas indicated in E, F, I and J.</p>", "links"=>[], "tags"=>["immunohistochemistry", "biopsies", "zalutumumab-injected", "treated", "humab-10f8"], "article_id"=>289810, "categories"=>["Cancer", "Developmental Biology", "Pharmacology", "Immunology"], "users"=>["Nannie Bangsgaard", "Mischa Houtkamp", "Danita H. Schuurhuis", "Paul W. H. I. Parren", "Ole Baadsgaard", "Hans W. M. Niessen", "Lone Skov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039706.g005", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histology_and_immunohistochemistry_of_biopsies_from_zalutumumab_injected_skin_treated_with_HuMab_10F8_or_untreated_/289810", "title"=>"Histology and immunohistochemistry of biopsies from zalutumumab-injected skin treated with HuMab-10F8 or untreated.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 03:28:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/618918"], "description"=>"<p>Injection schemes for the three different parts of the study are shown. Subjects were injected with different doses of zalutumumab at different sites, as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039706#pone-0039706-t001\" target=\"_blank\">Table 1</a>. Sc – screening of patient.</p>", "links"=>[], "tags"=>["immunology", "oncology", "pharmacology", "dermatology"], "article_id"=>289400, "categories"=>["Cancer", "Developmental Biology", "Pharmacology", "Immunology"], "users"=>["Nannie Bangsgaard", "Mischa Houtkamp", "Danita H. Schuurhuis", "Paul W. H. I. Parren", "Ole Baadsgaard", "Hans W. M. Niessen", "Lone Skov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039706.g001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Trial_design_/289400", "title"=>"Trial design.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 03:25:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/619421"], "description"=>"<p>a) semi-quantitative scoring: normal, acute inflammation (based on influx of neutrophils).</p>", "links"=>[], "tags"=>["follicles", "biopsies", "patients", "treated", "zalutumumab", "humab-10f8", "staining"], "article_id"=>289906, "categories"=>["Cancer", "Developmental Biology", "Pharmacology", "Immunology"], "users"=>["Nannie Bangsgaard", "Mischa Houtkamp", "Danita H. Schuurhuis", "Paul W. H. I. Parren", "Ole Baadsgaard", "Hans W. M. Niessen", "Lone Skov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0039706.t002", "stats"=>{"downloads"=>6, "page_views"=>69, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histological_features_of_hair_follicles_in_skin_biopsies_and_clinical_features_of_patients_treated_with_zalutumumab_zalutumumab_HuMab_10F8_or_saline_based_on_evaluation_of_HE_staining_and_clinical_observations_/289906", "title"=>"Histological features of hair follicles in skin biopsies and clinical features of patients treated with zalutumumab, zalutumumab + HuMab-10F8 or saline, based on evaluation of HE staining and clinical observations.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 03:29:02"}

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Relative Metric

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