Tumor Associated Macrophages Protect Colon Cancer Cells from TRAIL-Induced Apoptosis through IL-1β- Dependent Stabilization of Snail in Tumor Cells
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Tumor associated macrophages protect colon cancer cells from TRAIL-induced apoptosis through IL-1β- dependent stabilization of snail in tumor cells", "type"=>"journal", "authors"=>[{"first_name"=>"Pawan", "last_name"=>"Kaler", "scopus_author_id"=>"23667211100"}, {"first_name"=>"Vincent", "last_name"=>"Galea", "scopus_author_id"=>"36608008100"}, {"first_name"=>"Leonard", "last_name"=>"Augenlicht", "scopus_author_id"=>"7004774947"}, {"first_name"=>"Lidija", "last_name"=>"Klampfer", "scopus_author_id"=>"6603644637"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"359319308", "sgr"=>"77955410185", "issn"=>"19326203", "pmid"=>"20661477", "scopus"=>"2-s2.0-77955410185", "doi"=>"10.1371/journal.pone.0011700", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"459d70d8-d244-395e-a6d9-1dc99c742533", "abstract"=>"Background: We recently reported that colon tumor cells stimulate macrophages to release IL-1β, which in turn inactivates GSK3β and enhances Wnt signaling in colon cancer cells, generating a self-amplifying loop that promotes the growth of tumor cells. Principal Findings: Here we describe that macrophages protect HCT116 and Hke-3 colon cancer cells from TRAIL-induced apoptosis. Inactivation of IL-1β by neutralizing IL-1β antibody, or silencing of IL-1β in macrophages inhibited their ability to counter TRAIL-induced apoptosis. Accordingly, IL-1β was sufficient to inhibit TRAIL-induced apoptosis. TRAIL-induced collapse of the mitochondrial membrane potential (Δψ) and activation of caspases were prevented by macrophages or by recombinant IL-1β. Pharmacological inhibition of IL-1β release from macrophages by vitamin D3, a potent chemopreventive agent for colorectal cancer, restored the ability of TRAIL to induce apoptosis of tumor cells cultured with macrophages. Macrophages and IL-1β failed to inhibit TRAIL-induced apoptosis in HCT116 cells expressing dnIκB, dnAKT or dnTCF4, confirming that they oppose TRAIL-induced cell death through induction of Wnt signaling in tumor cells. We showed that macrophages and IL-1β stabilized Snail in tumor cells in an NF-κB/Wnt dependent manner and that Snail deficient tumor cells were not protected from TRAIL-induced apoptosis by macrophages or by IL-1β, demonstrating a crucial role of Snail in the resistance of tumor cells to TRAIL. Significance: We have identified a positive feedback loop between tumor cells and macrophages that propagates the growth and promotes the survival of colon cancer cells: tumor cells stimulate macrophages to secrete IL-1β, which in turn, promotes Wnt signaling and stabilizes Snail in tumor cells, conferring resistance to TRAIL. Vitamin D3 halts this amplifying loop by interfering with the release of IL-1β from macrophages. Accordingly, vitamin D3 sensitizes tumor cells to TRAIL-induced apoptosis, suggesting that the therapeutic efficacy of TRAIL could be augmented by this readily available chemopreventive agent.", "link"=>"http://www.mendeley.com/research/tumor-associated-macrophages-protect-colon-cancer-cells-trailinduced-apoptosis-through-il1%CE%B2-dependen", "reader_count"=>20, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>6, "Student > Master"=>5, "Lecturer"=>1, "Unspecified"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>6, "Student > Master"=>5, "Lecturer"=>1, "Unspecified"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Agricultural and Biological Sciences"=>12, "Medicine and Dentistry"=>3, "Chemistry"=>1, "Immunology and Microbiology"=>1, "Unspecified"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Unspecified"=>{"Unspecified"=>2}}, "group_count"=>0}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/77955410185"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/77955410185?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=77955410185&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=77955410185&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/77955410185", "dc:identifier"=>"SCOPUS_ID:77955410185", "eid"=>"2-s2.0-77955410185", "dc:title"=>"Tumor associated macrophages protect colon cancer cells from TRAIL-induced apoptosis through IL-1β- dependent stabilization of snail in tumor cells", "dc:creator"=>"Kaler P.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"5", "prism:issueIdentifier"=>"7", "prism:pageRange"=>nil, "prism:coverDate"=>"2010-08-13", "prism:coverDisplayDate"=>"2010", "prism:doi"=>"10.1371/journal.pone.0011700", "citedby-count"=>"47", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"Montefiore Medical Center", "affiliation-city"=>"New York", "affiliation-country"=>"United States"}], "pubmed-id"=>"20661477", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e11700", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0011700", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Counter

  • {"month"=>"7", "year"=>"2010", "pdf_views"=>"70", "xml_views"=>"38", "html_views"=>"195"}
  • {"month"=>"8", "year"=>"2010", "pdf_views"=>"70", "xml_views"=>"2", "html_views"=>"144"}
  • {"month"=>"9", "year"=>"2010", "pdf_views"=>"36", "xml_views"=>"1", "html_views"=>"90"}
  • {"month"=>"10", "year"=>"2010", "pdf_views"=>"39", "xml_views"=>"1", "html_views"=>"102"}
  • {"month"=>"11", "year"=>"2010", "pdf_views"=>"47", "xml_views"=>"0", "html_views"=>"162"}
  • {"month"=>"12", "year"=>"2010", "pdf_views"=>"33", "xml_views"=>"2", "html_views"=>"60"}
  • {"month"=>"1", "year"=>"2011", "pdf_views"=>"39", "xml_views"=>"2", "html_views"=>"99"}
  • {"month"=>"2", "year"=>"2011", "pdf_views"=>"31", "xml_views"=>"0", "html_views"=>"100"}
  • {"month"=>"3", "year"=>"2011", "pdf_views"=>"34", "xml_views"=>"0", "html_views"=>"89"}
  • {"month"=>"4", "year"=>"2011", "pdf_views"=>"25", "xml_views"=>"0", "html_views"=>"79"}
  • {"month"=>"5", "year"=>"2011", "pdf_views"=>"29", "xml_views"=>"1", "html_views"=>"63"}
  • {"month"=>"6", "year"=>"2011", "pdf_views"=>"28", "xml_views"=>"1", "html_views"=>"67"}
  • {"month"=>"7", "year"=>"2011", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"8", "year"=>"2011", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"63"}
  • {"month"=>"9", "year"=>"2011", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"51"}
  • {"month"=>"10", "year"=>"2011", "pdf_views"=>"26", "xml_views"=>"0", "html_views"=>"69"}
  • {"month"=>"11", "year"=>"2011", "pdf_views"=>"22", "xml_views"=>"0", "html_views"=>"68"}
  • {"month"=>"12", "year"=>"2011", "pdf_views"=>"32", "xml_views"=>"0", "html_views"=>"66"}
  • {"month"=>"1", "year"=>"2012", "pdf_views"=>"17", "xml_views"=>"1", "html_views"=>"58"}
  • {"month"=>"2", "year"=>"2012", "pdf_views"=>"27", "xml_views"=>"0", "html_views"=>"69"}
  • {"month"=>"3", "year"=>"2012", "pdf_views"=>"39", "xml_views"=>"0", "html_views"=>"86"}
  • {"month"=>"4", "year"=>"2012", "pdf_views"=>"20", "xml_views"=>"1", "html_views"=>"60"}
  • {"month"=>"5", "year"=>"2012", "pdf_views"=>"31", "xml_views"=>"1", "html_views"=>"83"}
  • {"month"=>"6", "year"=>"2012", "pdf_views"=>"43", "xml_views"=>"0", "html_views"=>"79"}
  • {"month"=>"7", "year"=>"2012", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"69"}
  • {"month"=>"8", "year"=>"2012", "pdf_views"=>"24", "xml_views"=>"6", "html_views"=>"65"}
  • {"month"=>"9", "year"=>"2012", "pdf_views"=>"28", "xml_views"=>"0", "html_views"=>"97"}
  • {"month"=>"10", "year"=>"2012", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"79"}
  • {"month"=>"11", "year"=>"2012", "pdf_views"=>"35", "xml_views"=>"0", "html_views"=>"121"}
  • {"month"=>"12", "year"=>"2012", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"77"}
  • {"month"=>"1", "year"=>"2013", "pdf_views"=>"23", "xml_views"=>"0", "html_views"=>"108"}
  • {"month"=>"2", "year"=>"2013", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"48"}
  • {"month"=>"3", "year"=>"2013", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"81"}
  • {"month"=>"4", "year"=>"2013", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"82"}
  • {"month"=>"5", "year"=>"2013", "pdf_views"=>"25", "xml_views"=>"0", "html_views"=>"73"}
  • {"month"=>"6", "year"=>"2013", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"95"}
  • {"month"=>"7", "year"=>"2013", "pdf_views"=>"25", "xml_views"=>"1", "html_views"=>"79"}
  • {"month"=>"8", "year"=>"2013", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"51"}
  • {"month"=>"9", "year"=>"2013", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"86"}
  • {"month"=>"10", "year"=>"2013", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"59"}
  • {"month"=>"11", "year"=>"2013", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"46"}
  • {"month"=>"12", "year"=>"2013", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"37"}
  • {"month"=>"1", "year"=>"2014", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"2", "year"=>"2014", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"58"}
  • {"month"=>"3", "year"=>"2014", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"90"}
  • {"month"=>"4", "year"=>"2014", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"92"}
  • {"month"=>"5", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"66"}
  • {"month"=>"6", "year"=>"2014", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"82"}
  • {"month"=>"7", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"52"}
  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"10", "xml_views"=>"2", "html_views"=>"42"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"45"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"34"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"45"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"27"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"55"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"17"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"38"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"18"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"55"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"79"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"83"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"89"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"84"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"78"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"31"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"38"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"23"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"29"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"33"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"33"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"40"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"20"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"9"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"4", "html_views"=>"13"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"11"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"6"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"9"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"4"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"4"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"2"}
  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"10", "year"=>"2019", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"6"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/840035"], "description"=>"<p>A: HCT116 and Hke-3 cells were transfected with TOP-FLASH reporter together with an empty vector (neo), or the increasing concentrations of Snail expression vector. The experiment was performed in triplicate. B: Tumor cells were transfected with NSP or Snail specific siRNA and were treated with IL-1β as indicated. The levels of Snail were determined by immunoblotting. C: Tumor cells were transfected with TOP-FLASH reporter together with NSP or Snail specific siRNA. Data represent the average of two independent experiments each performed in duplicate.</p>", "links"=>[], "tags"=>["regulates", "wnt"], "article_id"=>510497, "categories"=>["Cancer", "Cell Biology"], "users"=>["Pawan Kaler", "Vincent Galea", "Leonard Augenlicht", "Lidija Klampfer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0011700.g007", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Snail_regulates_Wnt_signaling_/510497", "title"=>"Snail regulates Wnt signaling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-07-22 00:08:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/839908"], "description"=>"<p><b>A:</b> Macrophages, IL-1β and TNFα stabilize Snail in a NF-κB/AKT/Wnt dependent manner. HCT116 cells were transfected with dnIκB, dnAKT or dnTCF4 and were treated with IL-1β or TNFα, or were cultured with THP1 macrophages as indicated. The levels of Snail and c-jun were determined by immunoblotting. <b>B:</b> The levels of Snail and pGSK3β were determined by immunoblotting in Hke-3 cells that were treated with IL-1β, TNFα or were co-cultured with macrophages in the absence or the presence of LY 294002 for 24 hours. <b>C</b>: HCT116 and Hke-3 cells were treated with TRAIL in the absence or the presence of IL-1β and LY294002, as indicated. The experiment was performed three times.</p>", "links"=>[], "tags"=>["stabilize", "snail"], "article_id"=>510370, "categories"=>["Cancer", "Cell Biology"], "users"=>["Pawan Kaler", "Vincent Galea", "Leonard Augenlicht", "Lidija Klampfer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0011700.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Macrophages_IL_1_946_and_TNF_945_stabilize_Snail_in_a_NF_954_B_AKT_Wnt_dependent_manner_/510370", "title"=>"Macrophages, IL-1β and TNFα stabilize Snail in a NF-κB/AKT/Wnt dependent manner.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-07-22 00:06:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/839501"], "description"=>"<p>A: HCT116 (average of 5 independent experiments) and Hke-3 cells (average of 4 independent experiments) were treated with TRAIL in the absence or the presence of macrophages or IL-1β (5 ng/ml) as indicated and the extent of apoptosis was determined after 7 hours. B: The mitochondrial membrane potential (MMP) was determined by JC1 staining 5 hours after treatment. C: Activation of caspase 8 and caspase-9 was determined in colon cancer cells treated with TRAIL (50 ng/ml) under conditions indicated. D: TRAIL- sensitive cancer cell lines were treated with TRAIL in the absence or the presence of human peripheral blood monocytes (Mo) and the extent of apoptosis was determined 7 hours after treatment. Data shown represent the average of 2 or 3 independent experiments.</p>", "links"=>[], "tags"=>["macrophage-derived", "factors", "colon", "cancer", "cells", "trail-induced"], "article_id"=>509956, "categories"=>["Cancer", "Cell Biology"], "users"=>["Pawan Kaler", "Vincent Galea", "Leonard Augenlicht", "Lidija Klampfer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0011700.g002", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Macrophages_and_macrophage_derived_factors_protect_colon_cancer_cells_from_TRAIL_induced_apoptosis_/509956", "title"=>"Macrophages and macrophage-derived factors protect colon cancer cells from TRAIL-induced apoptosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-07-22 02:45:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/418166", "https://ndownloader.figshare.com/files/418196", "https://ndownloader.figshare.com/files/418221", "https://ndownloader.figshare.com/files/418243"], "description"=>"<div><h3>Background</h3><p>We recently reported that colon tumor cells stimulate macrophages to release IL-1β, which in turn inactivates GSK3β and enhances Wnt signaling in colon cancer cells, generating a self-amplifying loop that promotes the growth of tumor cells.</p> <h3>Principal Findings</h3><p>Here we describe that macrophages protect HCT116 and Hke-3 colon cancer cells from TRAIL-induced apoptosis. Inactivation of IL-1β by neutralizing IL-1β antibody, or silencing of IL-1β in macrophages inhibited their ability to counter TRAIL-induced apoptosis. Accordingly, IL-1β was sufficient to inhibit TRAIL-induced apoptosis. TRAIL-induced collapse of the mitochondrial membrane potential (Δψ) and activation of caspases were prevented by macrophages or by recombinant IL-1β. Pharmacological inhibition of IL-1β release from macrophages by vitamin D<sub>3</sub>, a potent chemopreventive agent for colorectal cancer, restored the ability of TRAIL to induce apoptosis of tumor cells cultured with macrophages. Macrophages and IL-1β failed to inhibit TRAIL-induced apoptosis in HCT116 cells expressing dnIκB, dnAKT or dnTCF4, confirming that they oppose TRAIL-induced cell death through induction of Wnt signaling in tumor cells. We showed that macrophages and IL-1β stabilized Snail in tumor cells in an NF-κB/Wnt dependent manner and that Snail deficient tumor cells were not protected from TRAIL-induced apoptosis by macrophages or by IL-1β, demonstrating a crucial role of Snail in the resistance of tumor cells to TRAIL.</p> <h3>Significance</h3><p>We have identified a positive feedback loop between tumor cells and macrophages that propagates the growth and promotes the survival of colon cancer cells: tumor cells stimulate macrophages to secrete IL-1β, which in turn, promotes Wnt signaling and stabilizes Snail in tumor cells, conferring resistance to TRAIL. Vitamin D<sub>3</sub> halts this amplifying loop by interfering with the release of IL-1β from macrophages. Accordingly, vitamin D<sub>3</sub> sensitizes tumor cells to TRAIL-induced apoptosis, suggesting that the therapeutic efficacy of TRAIL could be augmented by this readily available chemopreventive agent.</p> </div>", "links"=>[], "tags"=>["macrophages", "colon", "cancer", "cells", "trail-induced", "apoptosis", "stabilization", "snail"], "article_id"=>142566, "categories"=>["Cancer", "Cell Biology"], "users"=>["Pawan Kaler", "Vincent Galea", "Leonard Augenlicht", "Lidija Klampfer"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0011700.s001", "https://dx.doi.org/10.1371/journal.pone.0011700.s002", "https://dx.doi.org/10.1371/journal.pone.0011700.s003", "https://dx.doi.org/10.1371/journal.pone.0011700.s004"], "stats"=>{"downloads"=>6, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Tumor_Associated_Macrophages_Protect_Colon_Cancer_Cells_from_TRAIL_Induced_Apoptosis_through_IL_1_Dependent_Stabilization_of_Snail_in_Tumor_Cells/142566", "title"=>"Tumor Associated Macrophages Protect Colon Cancer Cells from TRAIL-Induced Apoptosis through IL-1β- Dependent Stabilization of Snail in Tumor Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-07-22 00:42:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/839628"], "description"=>"<p>A and B: HCT116 cells were cultured with THP1 macrophages with silenced IL-1β or STAT1 expression and were treated with TRAIL as indicated. IL-1β was neutralized by anti-IL-1β specific antibody. Pictures were taken (A) and the amount of apoptosis (B) was determined after 7 hours. Data shown in B represent the average of three independent experiments. C and D: Studies by Gyorffy <i>et al</i> (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011700#pone.0011700-Gyorffy1\" target=\"_blank\">[29]</a>, C) and by Khambata-Ford <i>et al</i> (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011700#pone.0011700-KhambataFord1\" target=\"_blank\">[30]</a>, D) were surveyed through Oncomine and indicate that cell lines (C) and primary colon cancers (D) with higher levels of IL-1βdisplay resistance to therapeutic agents, such as vinblastine, doxorubicin and cetuximab (CTX).</p>", "links"=>[], "tags"=>["cells", "trail-induced"], "article_id"=>510089, "categories"=>["Cancer", "Cell Biology"], "users"=>["Pawan Kaler", "Vincent Galea", "Leonard Augenlicht", "Lidija Klampfer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0011700.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IL_1_946_is_sufficient_and_required_to_protect_cells_from_TRAIL_induced_apoptosis_/510089", "title"=>"IL-1β is sufficient and required to protect cells from TRAIL-induced apoptosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-07-22 00:01:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/839825"], "description"=>"<p>A and B: HCT116 expressing dnIκB, dnAKT or dnTCF4 were treated with TRAIL under indicated conditions and the amount of apoptosis was determined by propidium iodide staining. A: Data represent the average of 5 independent experiments. B: The extent of caspase activation and the cleavage of PARP and β-catenin were determined in cell lysates by immunoblotting. C: The localization of β-catenin was determined by immunofluorescence in HCT116 cells treated with TRAIL in the absence or the presence of IL-1β or TNFα.</p>", "links"=>[], "tags"=>["prosurvival", "macrophages"], "article_id"=>510288, "categories"=>["Cancer", "Cell Biology"], "users"=>["Pawan Kaler", "Vincent Galea", "Leonard Augenlicht", "Lidija Klampfer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0011700.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Wnt_is_required_for_the_prosurvival_activity_of_macrophages_and_IL_1_946_/510288", "title"=>"Wnt is required for the prosurvival activity of macrophages and IL-1β.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-07-22 00:04:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/840316"], "description"=>"<p>Tumor cells activate macrophages to secrete IL-1β which in a NF-κB/AKT dependent manner inactivates GSK3β and thus promotes Wnt signaling in tumor cells. Elevated levels of c-myc contribute to enhanced growth of tumor cells, while increased levels of Snail contribute to enhanced Wnt signaling, protect cells from TRAIL induced apoptosis, and are likely to contribute to the epithelial mesenchymal transition (EMT) and enhanced metastatic potential of tumor cells.</p>", "links"=>[], "tags"=>["cells", "macrophages", "propagates", "cancer"], "article_id"=>510773, "categories"=>["Cancer", "Cell Biology"], "users"=>["Pawan Kaler", "Vincent Galea", "Leonard Augenlicht", "Lidija Klampfer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0011700.g009", "stats"=>{"downloads"=>1, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Crosstalk_between_tumor_cells_and_macrophages_which_propagates_the_growth_and_survival_of_cancer_cells_/510773", "title"=>"Crosstalk between tumor cells and macrophages which propagates the growth and survival of cancer cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-07-22 00:12:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/839710"], "description"=>"<p>A: The amount of apoptosis was determined in HCT116 cells treated with TRAIL under indicated conditions. Error bars were derived from 2 independent experiments. B: The effect of vitamin D<sub>3</sub> on TRAIL-induced activation of caspases and the cleavage of PARP and β-catenin was determined by immunoblotting.</p>", "links"=>[], "tags"=>["inhibition", "secretion", "inhibits", "prosurvival"], "article_id"=>510169, "categories"=>["Cancer", "Cell Biology"], "users"=>["Pawan Kaler", "Vincent Galea", "Leonard Augenlicht", "Lidija Klampfer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0011700.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pharmacological_inhibition_of_IL_1_secretion_by_Vitamin_D_3_inhibits_the_prosurvival_function_of_macrophages_/510169", "title"=>"Pharmacological inhibition of IL-1β secretion by Vitamin D<sub>3</sub> inhibits the prosurvival function of macrophages.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-07-22 00:02:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/839403"], "description"=>"<p>A and B: HCT116 and Hke-3 cells were seeded at a density of 200 cells per well of a six well plate in the absence or the presence of macrophages (1600/well) or IL-1β, and were treated with TRAIL for 4 hours. The results shown in B represent the average of two independent experiments each performed in duplicate.</p>", "links"=>[], "tags"=>["counteract", "trail-induced", "inhibition", "colon", "cancer"], "article_id"=>509860, "categories"=>["Cancer", "Cell Biology"], "users"=>["Pawan Kaler", "Vincent Galea", "Leonard Augenlicht", "Lidija Klampfer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0011700.g001", "stats"=>{"downloads"=>0, "page_views"=>28, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Macrophages_and_IL_1_946_counteract_TRAIL_induced_inhibition_of_colon_cancer_growth_/509860", "title"=>"Macrophages and IL-1β counteract TRAIL-induced inhibition of colon cancer growth.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-07-22 02:44:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/840160"], "description"=>"<p>A: HCT116 and Hke-3 cells were transfected with NSP or Snail specific siRNA and were treated with TRAIL in the absence or the presence of macrophages or IL-1β as indicated. Data represent the average of two independent experiments. B and C: Silencing of IL-1β or STAT1 (B) in macrophages, or treatment with vitamin D<sub>3</sub> (C) abrogates the ability of macrophages to stabilize Snail in colon cancer cells.</p>", "links"=>[], "tags"=>["mediates", "anti-apoptotic", "macrophages"], "article_id"=>510621, "categories"=>["Cancer", "Cell Biology"], "users"=>["Pawan Kaler", "Vincent Galea", "Leonard Augenlicht", "Lidija Klampfer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0011700.g008", "stats"=>{"downloads"=>1, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Snail_mediates_the_anti_apoptotic_activity_of_macrophages_and_IL_1_946_/510621", "title"=>"Snail mediates the anti-apoptotic activity of macrophages and IL-1β.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-07-22 00:10:21"}

PMC Usage Stats | Further Information

  • {"scanned-page-browse"=>"0", "month"=>"7", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"3", "unique-ip"=>"4", "pdf"=>"3", "year"=>"2010", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"8", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"5", "full-text"=>"104", "year"=>"2010", "pdf"=>"72", "unique-ip"=>"95", "figure"=>"16", "scanned-summary"=>"0", "supp-data"=>"3"}
  • {"scanned-page-browse"=>"0", "month"=>"9", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"63", "unique-ip"=>"59", "pdf"=>"55", "year"=>"2010", "figure"=>"9", "scanned-summary"=>"0", "supp-data"=>"9"}
  • {"month"=>"10", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"61", "year"=>"2010", "pdf"=>"47", "unique-ip"=>"52", "figure"=>"7", "scanned-summary"=>"0", "supp-data"=>"6"}
  • {"scanned-page-browse"=>"0", "month"=>"11", "cited-by"=>"0", "abstract"=>"3", "full-text"=>"68", "unique-ip"=>"60", "pdf"=>"53", "year"=>"2010", "figure"=>"17", "scanned-summary"=>"0", "supp-data"=>"12"}
  • {"month"=>"12", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"41", "year"=>"2010", "pdf"=>"45", "unique-ip"=>"42", "figure"=>"5", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"1", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"49", "unique-ip"=>"47", "pdf"=>"38", "year"=>"2011", "figure"=>"7", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"2", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"3", "full-text"=>"41", "year"=>"2011", "pdf"=>"31", "unique-ip"=>"42", "figure"=>"7", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"3", "cited-by"=>"0", "abstract"=>"4", "full-text"=>"39", "unique-ip"=>"39", "pdf"=>"28", "year"=>"2011", "figure"=>"5", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"4", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"24", "year"=>"2011", "pdf"=>"22", "unique-ip"=>"27", "figure"=>"5", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"5", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"30", "unique-ip"=>"36", "pdf"=>"30", "year"=>"2011", "figure"=>"8", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"23", "year"=>"2011", "pdf"=>"26", "unique-ip"=>"28", "figure"=>"7", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"7", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"25", "unique-ip"=>"21", "pdf"=>"21", "year"=>"2011", "figure"=>"5", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"8", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"21", "year"=>"2011", "pdf"=>"11", "unique-ip"=>"25", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"9", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"25", "unique-ip"=>"21", "pdf"=>"15", "year"=>"2011", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"10", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"28", "year"=>"2011", "pdf"=>"17", "unique-ip"=>"22", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"11", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"20", "unique-ip"=>"23", "pdf"=>"17", "year"=>"2011", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"12", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"19", "year"=>"2011", "pdf"=>"7", "unique-ip"=>"20", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"2"}
  • {"scanned-page-browse"=>"0", "month"=>"1", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"15", "unique-ip"=>"20", "pdf"=>"15", "year"=>"2012", "figure"=>"7", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"2", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"18", "year"=>"2012", "pdf"=>"10", "unique-ip"=>"21", "figure"=>"6", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"3", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"21", "unique-ip"=>"22", "pdf"=>"14", "year"=>"2012", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"4", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"22", "year"=>"2012", "pdf"=>"11", "unique-ip"=>"23", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"5", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"16", "unique-ip"=>"17", "pdf"=>"8", "year"=>"2012", "figure"=>"8", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"3", "full-text"=>"17", "year"=>"2012", "pdf"=>"9", "unique-ip"=>"20", "figure"=>"9", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"7"}
  • {"unique-ip"=>"17", "full-text"=>"18", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"8"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"9"}
  • {"unique-ip"=>"21", "full-text"=>"20", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"10"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"12"}
  • {"unique-ip"=>"14", "full-text"=>"12", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"1"}
  • {"unique-ip"=>"25", "full-text"=>"25", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"3", "cited-by"=>"1", "year"=>"2013", "month"=>"3"}
  • {"unique-ip"=>"12", "full-text"=>"13", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"2"}
  • {"unique-ip"=>"16", "full-text"=>"20", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"11"}
  • {"unique-ip"=>"24", "full-text"=>"26", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
  • {"unique-ip"=>"29", "full-text"=>"25", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"12", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
  • {"unique-ip"=>"13", "full-text"=>"15", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"15", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
  • {"unique-ip"=>"10", "full-text"=>"14", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
  • {"unique-ip"=>"13", "full-text"=>"15", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
  • {"unique-ip"=>"16", "full-text"=>"13", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
  • {"unique-ip"=>"20", "full-text"=>"26", "pdf"=>"183", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"16", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"2", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"17", "full-text"=>"14", "pdf"=>"13", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"unique-ip"=>"17", "full-text"=>"12", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"15", "full-text"=>"12", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"15", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"34", "full-text"=>"35", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"29", "full-text"=>"25", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"14", "full-text"=>"15", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"12", "full-text"=>"9", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"14", "full-text"=>"17", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"13", "full-text"=>"11", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"15", "full-text"=>"12", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"22", "full-text"=>"18", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"8", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"14", "full-text"=>"11", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"10", "full-text"=>"14", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"17", "full-text"=>"16", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"13", "full-text"=>"14", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"15", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"12", "full-text"=>"13", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"7", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"10", "full-text"=>"12", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"16", "full-text"=>"15", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"7", "full-text"=>"9", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"13", "full-text"=>"14", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"6", "full-text"=>"8", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"14", "full-text"=>"16", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"20", "full-text"=>"18", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"10", "full-text"=>"7", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"14", "full-text"=>"15", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"15", "full-text"=>"15", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"16", "full-text"=>"15", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}

Relative Metric

{"start_date"=>"2010-01-01T00:00:00Z", "end_date"=>"2010-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Immunology", "average_usage"=>[266, 530, 683, 806, 930, 1032, 1122, 1207, 1292, 1362, 1433, 1495, 1565, 1621, 1680, 1737, 1792, 1851, 1901, 1967, 2022, 2075, 2150, 2203, 2250, 2314, 2367, 2416, 2472, 2531, 2603, 2651, 2707, 2756, 2800, 2877, 2936, 2986, 3036, 3083, 3131, 3191, 3253, 3313, 3376, 3437, 3496, 3556]}, {"subject_area"=>"/Biology and life sciences/Nutrition", "average_usage"=>[333, 622, 806, 950, 1091, 1200, 1320, 1416, 1501, 1597, 1702, 1777, 1853, 1949, 2049, 2127, 2223, 2314, 2439, 2517, 2587, 2739, 2804, 2885, 2967, 3034, 3138, 3236, 3331, 3387, 3485, 3579, 3667, 3745, 3810, 3898, 3955, 4027, 4082, 4134, 4213, 4287, 4369, 4443, 4509, 4575, 4632, 4681, 4796]}, {"subject_area"=>"/Medicine and health sciences/Immunology", "average_usage"=>[267, 555, 705, 829, 955, 1058, 1158, 1248, 1324, 1404, 1476, 1548, 1626, 1706, 1765, 1821, 1875, 1937, 2010, 2063, 2130, 2192, 2264, 2316, 2359, 2409, 2484, 2546, 2631, 2695, 2752, 2816, 2871, 2935, 2987, 3041, 3095, 3153, 3207, 3286, 3353, 3392, 3439, 3478, 3531, 3584, 3649, 3714]}, {"subject_area"=>"/Medicine and health sciences/Nutrition", "average_usage"=>[319, 609, 799, 941, 1085, 1205, 1316, 1426, 1517, 1615, 1714, 1790, 1859, 1949, 2060, 2153, 2229, 2333, 2423, 2525, 2610, 2698, 2790, 2871, 2956, 3008, 3085, 3153, 3221, 3294, 3410, 3505, 3612, 3682, 3731, 3790, 3865, 3961, 4035, 4101, 4160, 4229, 4283, 4344, 4402, 4459, 4510, 4573, 4677]}]}
Loading … Spinner
There are currently no alerts