Drug-Tolerant Cancer Cells Show Reduced Tumor-Initiating Capacity: Depletion of CD44+ Cells and Evidence for Epigenetic Mechanisms
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Drug-tolerant cancer cells show reduced tumor-initiating capacity: Depletion of CD44 + cells and evidence for epigenetic mechanisms", "type"=>"journal", "authors"=>[{"first_name"=>"Hong", "last_name"=>"Yan", "scopus_author_id"=>"35328765400"}, {"first_name"=>"Xin", "last_name"=>"Chen", "scopus_author_id"=>"37100951100"}, {"first_name"=>"Qiuping", "last_name"=>"Zhang", "scopus_author_id"=>"8247587500"}, {"first_name"=>"Jichao", "last_name"=>"Qin", "scopus_author_id"=>"7402896516"}, {"first_name"=>"Hangwen", "last_name"=>"Li", "scopus_author_id"=>"27169799200"}, {"first_name"=>"Can", "last_name"=>"Liu", "scopus_author_id"=>"37061375300"}, {"first_name"=>"Tammy", "last_name"=>"Calhoun-Davis", "scopus_author_id"=>"17343221200"}, {"first_name"=>"Luis", "last_name"=>"Della Coletta", "scopus_author_id"=>"6507168621"}, {"first_name"=>"Jim", "last_name"=>"Klostergaard", "scopus_author_id"=>"7005542764"}, {"first_name"=>"Izabela", "last_name"=>"Fokt", "scopus_author_id"=>"35475451900"}, {"first_name"=>"Stanislaw", "last_name"=>"Skora", "scopus_author_id"=>"6602945214"}, {"first_name"=>"Waldemar", "last_name"=>"Priebe", "scopus_author_id"=>"7007036636"}, {"first_name"=>"Yongyi", "last_name"=>"Bi", "scopus_author_id"=>"7102641894"}, {"first_name"=>"Dean G.", "last_name"=>"Tang", "scopus_author_id"=>"7401987280"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pmid"=>"21935404", "pui"=>"362567466", "scopus"=>"2-s2.0-80052829163", "doi"=>"10.1371/journal.pone.0024397", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"80052829163"}, "id"=>"d0c4d286-7347-38ca-a106-6dfb8fcfc4cb", "abstract"=>"Cancer stem cells (CSCs) possess high tumor-initiating capacity and have been reported to be resistant to therapeutics. Vice versa, therapy-resistant cancer cells seem to manifest CSC phenotypes and properties. It has been generally assumed that drug-resistant cancer cells may all be CSCs although the generality of this assumption is unknown. Here, we chronically treated Du145 prostate cancer cells with etoposide, paclitaxel and some experimental drugs (i.e., staurosporine and 2 paclitaxel analogs), which led to populations of drug-tolerant cells (DTCs). Surprisingly, these DTCs, when implanted either subcutaneously or orthotopically into NOD/SCID mice, exhibited much reduced tumorigenicity or were even non-tumorigenic. Drug-tolerant DLD1 colon cancer cells selected by a similar chronic selection protocol also displayed reduced tumorigenicity whereas drug-tolerant UC14 bladder cancer cells demonstrated either increased or decreased tumor-regenerating capacity. Drug-tolerant Du145 cells demonstrated low proliferative and clonogenic potential and were virtually devoid of CD44(+) cells. Prospective knockdown of CD44 in Du145 cells inhibited cell proliferation and tumor regeneration, whereas restoration of CD44 expression in drug-tolerant Du145 cells increased cell proliferation and partially increased tumorigenicity. Interestingly, drug-tolerant Du145 cells showed both increases and decreases in many \"stemness\" genes. Finally, evidence was provided that chronic drug exposure generated DTCs via epigenetic mechanisms involving molecules such as CD44 and KDM5A. Our results thus reveal that 1) not all DTCs are necessarily CSCs; 2) conventional chemotherapeutic drugs such as taxol and etoposide may directly target CD44(+) tumor-initiating cells; and 3) DTCs generated via chronic drug selection involve epigenetic mechanisms.", "link"=>"http://www.mendeley.com/research/drugtolerant-cancer-cells-show-reduced-tumorinitiating-capacity-depletion-cd44-cells-evidence-epigen", "reader_count"=>50, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>2, "Researcher"=>18, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>2, "Other"=>3, "Student > Master"=>4, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>2, "Researcher"=>18, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>2, "Other"=>3, "Student > Master"=>4, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>6, "Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>22, "Medicine and Dentistry"=>11, "Chemistry"=>2, "Decision Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>11}, "Chemistry"=>{"Chemistry"=>2}, "Decision Sciences"=>{"Decision Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>22}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Unspecified"=>{"Unspecified"=>6}}, "reader_count_by_country"=>{"Iran"=>1, "United States"=>1, "Egypt"=>1, "Poland"=>1, "France"=>1}, "group_count"=>2}

CrossRef

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/80052829163"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/80052829163?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=80052829163&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=80052829163&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/80052829163", "dc:identifier"=>"SCOPUS_ID:80052829163", "eid"=>"2-s2.0-80052829163", "dc:title"=>"Drug-tolerant cancer cells show reduced tumor-initiating capacity: Depletion of CD44 <sup>+</sup> cells and evidence for epigenetic mechanisms", "dc:creator"=>"Yan H.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"6", "prism:issueIdentifier"=>"9", "prism:pageRange"=>nil, "prism:coverDate"=>"2011-09-15", "prism:coverDisplayDate"=>"15 September 2011", "prism:doi"=>"10.1371/journal.pone.0024397", "citedby-count"=>"28", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"University of Texas M. D. Anderson Cancer Center", "affiliation-city"=>"Houston", "affiliation-country"=>"United States"}, {"@_fa"=>"true", "affilname"=>"Wuhan University", "affiliation-city"=>"Wuhan", "affiliation-country"=>"China"}], "pubmed-id"=>"21935404", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e24397", "source-id"=>"10600153309"}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0024397", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Counter

  • {"month"=>"9", "year"=>"2011", "pdf_views"=>"99", "xml_views"=>"4", "html_views"=>"301"}
  • {"month"=>"10", "year"=>"2011", "pdf_views"=>"72", "xml_views"=>"1", "html_views"=>"115"}
  • {"month"=>"11", "year"=>"2011", "pdf_views"=>"51", "xml_views"=>"0", "html_views"=>"95"}
  • {"month"=>"12", "year"=>"2011", "pdf_views"=>"53", "xml_views"=>"16", "html_views"=>"84"}
  • {"month"=>"1", "year"=>"2012", "pdf_views"=>"79", "xml_views"=>"41", "html_views"=>"71"}
  • {"month"=>"2", "year"=>"2012", "pdf_views"=>"46", "xml_views"=>"16", "html_views"=>"59"}
  • {"month"=>"3", "year"=>"2012", "pdf_views"=>"38", "xml_views"=>"13", "html_views"=>"56"}
  • {"month"=>"4", "year"=>"2012", "pdf_views"=>"35", "xml_views"=>"13", "html_views"=>"58"}
  • {"month"=>"5", "year"=>"2012", "pdf_views"=>"27", "xml_views"=>"0", "html_views"=>"60"}
  • {"month"=>"6", "year"=>"2012", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"61"}
  • {"month"=>"7", "year"=>"2012", "pdf_views"=>"40", "xml_views"=>"0", "html_views"=>"86"}
  • {"month"=>"8", "year"=>"2012", "pdf_views"=>"34", "xml_views"=>"5", "html_views"=>"72"}
  • {"month"=>"9", "year"=>"2012", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"54"}
  • {"month"=>"10", "year"=>"2012", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"73"}
  • {"month"=>"11", "year"=>"2012", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"43"}
  • {"month"=>"12", "year"=>"2012", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"1", "year"=>"2013", "pdf_views"=>"23", "xml_views"=>"0", "html_views"=>"63"}
  • {"month"=>"2", "year"=>"2013", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"44"}
  • {"month"=>"3", "year"=>"2013", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"4", "year"=>"2013", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"5", "year"=>"2013", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"6", "year"=>"2013", "pdf_views"=>"21", "xml_views"=>"1", "html_views"=>"43"}
  • {"month"=>"7", "year"=>"2013", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"36"}
  • {"month"=>"8", "year"=>"2013", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"9", "year"=>"2013", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"10", "year"=>"2013", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"47"}
  • {"month"=>"11", "year"=>"2013", "pdf_views"=>"10", "xml_views"=>"2", "html_views"=>"37"}
  • {"month"=>"12", "year"=>"2013", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"72"}
  • {"month"=>"1", "year"=>"2014", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"55"}
  • {"month"=>"2", "year"=>"2014", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"56"}
  • {"month"=>"3", "year"=>"2014", "pdf_views"=>"13", "xml_views"=>"3", "html_views"=>"67"}
  • {"month"=>"4", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"61"}
  • {"month"=>"5", "year"=>"2014", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"66"}
  • {"month"=>"6", "year"=>"2014", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"75"}
  • {"month"=>"7", "year"=>"2014", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"67"}
  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"1", "xml_views"=>"2", "html_views"=>"58"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"38"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"56"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"23"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"2", "html_views"=>"26"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"12"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"25"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"25"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"66"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"91"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"64"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"83"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"83"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"57"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"37"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"25"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"36"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"21"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"18"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"1", "xml_views"=>"1", "html_views"=>"18"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"2", "html_views"=>"16"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"22"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"5"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/370898", "https://ndownloader.figshare.com/files/370909"], "description"=>"<div><p>Cancer stem cells (CSCs) possess high tumor-initiating capacity and have been reported to be resistant to therapeutics. Vice versa, therapy-resistant cancer cells seem to manifest CSC phenotypes and properties. It has been generally assumed that drug-resistant cancer cells may all be CSCs although the generality of this assumption is unknown. Here, we chronically treated Du145 prostate cancer cells with etoposide, paclitaxel and some experimental drugs (i.e., staurosporine and 2 paclitaxel analogs), which led to populations of drug-tolerant cells (DTCs). Surprisingly, these DTCs, when implanted either subcutaneously or orthotopically into NOD/SCID mice, exhibited much reduced tumorigenicity or were even non-tumorigenic. Drug-tolerant DLD1 colon cancer cells selected by a similar chronic selection protocol also displayed reduced tumorigenicity whereas drug-tolerant UC14 bladder cancer cells demonstrated either increased or decreased tumor-regenerating capacity. Drug-tolerant Du145 cells demonstrated low proliferative and clonogenic potential and were virtually devoid of CD44<sup>+</sup> cells. Prospective knockdown of CD44 in Du145 cells inhibited cell proliferation and tumor regeneration, whereas restoration of CD44 expression in drug-tolerant Du145 cells increased cell proliferation and partially increased tumorigenicity. Interestingly, drug-tolerant Du145 cells showed both increases and decreases in many “stemness” genes. Finally, evidence was provided that chronic drug exposure generated DTCs via epigenetic mechanisms involving molecules such as CD44 and KDM5A. Our results thus reveal that 1) not all DTCs are necessarily CSCs; 2) conventional chemotherapeutic drugs such as taxol and etoposide may directly target CD44<sup>+</sup> tumor-initiating cells; and 3) DTCs generated via chronic drug selection involve epigenetic mechanisms.</p> </div>", "links"=>[], "tags"=>["drug-tolerant", "cancer", "cells", "reduced", "tumor-initiating", "depletion", "epigenetic", "mechanisms"], "article_id"=>133269, "categories"=>["Cancer", "Cell Biology", "Genetics"], "users"=>["Hong Yan", "Xin Chen", "Qiuping Zhang", "Jichao Qin", "Hangwen Li", "Can Liu", "Tammy Calhoun-Davis", "Luis Della Coletta", "Jim Klostergaard", "Izabela Fokt", "Stanislaw Skora", "Waldemar Priebe", "Yongyi Bi", "Dean G. Tang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0024397.s001", "https://dx.doi.org/10.1371/journal.pone.0024397.s002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Drug_Tolerant_Cancer_Cells_Show_Reduced_Tumor_Initiating_Capacity_Depletion_of_CD44_Cells_and_Evidence_for_Epigenetic_Mechanisms/133269", "title"=>"Drug-Tolerant Cancer Cells Show Reduced Tumor-Initiating Capacity: Depletion of CD44<sup>+</sup> Cells and Evidence for Epigenetic Mechanisms", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-09-15 00:54:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/735490"], "description"=>"<p>A–B. Parental Du145 and drug-tolerant Du145 cell lines selected with two clinical drugs (A) or three experimental drugs (B) were exposed, side-by-side, to the respective selection drugs (e.g., Du145-VP16 cells to VP16 and Du145-Paclitaxel cells to paclitaxel) at the concentrations (transformed into logarithm) indicated. Y-axis represents cell growth inhibition (%). C. Tabulated presentations of IC<sub>50</sub> values (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024397#s2\" target=\"_blank\">Materials & Methods</a>) and corresponding 95% CI (confidence interval) of Du145 cells and drugs-tolerant Du145 cells in response to the five drugs indicated. Values were calculated from data obtained in A and B.</p>", "links"=>[], "tags"=>["du145", "cells", "resistant"], "article_id"=>405822, "categories"=>["Cancer", "Cell Biology", "Genetics"], "users"=>["Hong Yan", "Xin Chen", "Qiuping Zhang", "Jichao Qin", "Hangwen Li", "Can Liu", "Tammy Calhoun-Davis", "Luis Della Coletta", "Jim Klostergaard", "Izabela Fokt", "Stanislaw Skora", "Waldemar Priebe", "Yongyi Bi", "Dean G. Tang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0024397.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Drug_tolerant_Du145_cells_were_more_resistant_to_the_selection_drugs_/405822", "title"=>"Drug-tolerant Du145 cells were more resistant to the selection drugs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-15 01:37:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/735657"], "description"=>"<p>Du145-VP16 cells were treated with paclitaxel (A), STS (B), and doxorubicin (Dox; C) at the concentrations [log] indicated. Results are presented as % inhibition and IC<sub>50</sub> (D) were determined as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024397#pone-0024397-g001\" target=\"_blank\">Figure 1</a>.</p>", "links"=>[], "tags"=>["du145", "cells", "cross-resistant", "non-selecting"], "article_id"=>405990, "categories"=>["Cancer", "Cell Biology", "Genetics"], "users"=>["Hong Yan", "Xin Chen", "Qiuping Zhang", "Jichao Qin", "Hangwen Li", "Can Liu", "Tammy Calhoun-Davis", "Luis Della Coletta", "Jim Klostergaard", "Izabela Fokt", "Stanislaw Skora", "Waldemar Priebe", "Yongyi Bi", "Dean G. Tang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0024397.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Drug_tolerant_Du145_cells_were_cross_resistant_to_non_selecting_drugs_/405990", "title"=>"Drug-tolerant Du145 cells were cross-resistant to non-selecting drugs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-15 01:39:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/735770"], "description"=>"<p>Parental and drug-tolerant DLD1 cell lines selected with optimal concentrations (see Text) of VP16, paclitaxel, WP1102, and WP1103, were exposed, side-by-side, to the respective selection drugs at the concentrations (transformed into logarithm) indicated (A). Y-axis represents cell growth inhibition (%). B. Tabulated presentations of IC<sub>50</sub> values and corresponding 95% CI (confidence of intervals) of parental DLD1 cells and drug-tolerant DLD1 lines in response to both selecting and non-selecting drugs.</p>", "links"=>[], "tags"=>["dld1", "cells", "resistant", "selecting", "non-selecting"], "article_id"=>406104, "categories"=>["Cancer", "Cell Biology", "Genetics"], "users"=>["Hong Yan", "Xin Chen", "Qiuping Zhang", "Jichao Qin", "Hangwen Li", "Can Liu", "Tammy Calhoun-Davis", "Luis Della Coletta", "Jim Klostergaard", "Izabela Fokt", "Stanislaw Skora", "Waldemar Priebe", "Yongyi Bi", "Dean G. Tang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0024397.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Drug_tolerant_DLD1_cells_were_resistant_to_selecting_and_non_selecting_drugs_/406104", "title"=>"Drug-tolerant DLD1 cells were resistant to selecting and non-selecting drugs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-15 01:41:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/735951"], "description"=>"<p>A. GFP-tagged parental or drug-tolerant Du145 cells were implanted (500,000 cells/injection), in 50% Matrigel, in the DP of NOD/SCID mice. All animals were terminated 75 days post implantation. Shown are tumor incidence and tumor weights (mean ± S.D; statistics not applicable due to relatively small numbers of animals). B–C. Representative tumor and organ images from a tumor-bearing animal in the Du145 (B) and Du145-VP16 (C) group, respectively. All images were acquired using a Nikon microdissecting epifluorescence microscope at 0.75× and the boxed area in B (the lung GFP image) represents an enlargement showing GFP<sup>+</sup> spots in the lung.</p>", "links"=>[], "tags"=>["implanted", "drug-tolerant", "du145", "cells", "showed", "reduced", "tumorigenic", "metastatic"], "article_id"=>406283, "categories"=>["Cancer", "Cell Biology", "Genetics"], "users"=>["Hong Yan", "Xin Chen", "Qiuping Zhang", "Jichao Qin", "Hangwen Li", "Can Liu", "Tammy Calhoun-Davis", "Luis Della Coletta", "Jim Klostergaard", "Izabela Fokt", "Stanislaw Skora", "Waldemar Priebe", "Yongyi Bi", "Dean G. Tang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0024397.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Orthotopically_implanted_drug_tolerant_Du145_cells_showed_reduced_tumorigenic_and_metastatic_potential_/406283", "title"=>"Orthotopically implanted drug-tolerant Du145 cells showed reduced tumorigenic and metastatic potential.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-15 01:44:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/736084"], "description"=>"<p>A. Quantification of numbers of viable cells. Parent and drug-tolerant Du145 cells were plated, in quadruplicate, in 12-well plates (5,000 cells/well) and viable cells were quantified using Trypan blue exclusion assay 10 days post plating. B. Quantification of % BrdU<sup>+</sup> cells (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024397#s2\" target=\"_blank\">Materials & Methods</a>). C. Determination of cloning efficiency. Parent and drug-tolerant Du145 cells were plated, in quadruplicate, in 6-well plates (100 cells/well) with fresh medium replenished every 3 days. The numbers of holoclones and meroclones were determined 10 days post plating. In all data, bars represent the mean ± S.D and statistical analyses were conducted using Student <i>t</i>-test (*, P<0.05; **, P<0.01).</p>", "links"=>[], "tags"=>["du145", "cells", "proliferative", "showed", "cloning"], "article_id"=>406422, "categories"=>["Cancer", "Cell Biology", "Genetics"], "users"=>["Hong Yan", "Xin Chen", "Qiuping Zhang", "Jichao Qin", "Hangwen Li", "Can Liu", "Tammy Calhoun-Davis", "Luis Della Coletta", "Jim Klostergaard", "Izabela Fokt", "Stanislaw Skora", "Waldemar Priebe", "Yongyi Bi", "Dean G. Tang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0024397.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Drug_tolerant_Du145_cells_were_less_proliferative_and_showed_low_cloning_efficiency_/406422", "title"=>"Drug-tolerant Du145 cells were less proliferative and showed low cloning efficiency.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-15 01:47:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/736217"], "description"=>"<p>A. Whole cell lysate from the cell types indicated was used in Western blotting of p21, p27, Bcl-2, and hTERT and the blot was reprobed for β-actin. NS, non-specific. B. Western blotting of CD44 and ABCG2. The blot was reprobed for β-actin and GAPDH. C–D. Du145 and drug-tolerant Du145 cells were plated on glass coverslips and stained for CD44 using monoclonal antibody. Shown are representative images (C) and quantification of CD44<sup>+</sup> cells (D; mean ± S.D, *, P<0.01).</p>", "links"=>[], "tags"=>["changes", "reduced", "cells", "drug-tolerant", "du145"], "article_id"=>406551, "categories"=>["Cancer", "Cell Biology", "Genetics"], "users"=>["Hong Yan", "Xin Chen", "Qiuping Zhang", "Jichao Qin", "Hangwen Li", "Can Liu", "Tammy Calhoun-Davis", "Luis Della Coletta", "Jim Klostergaard", "Izabela Fokt", "Stanislaw Skora", "Waldemar Priebe", "Yongyi Bi", "Dean G. Tang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0024397.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Molecular_changes_and_reduced_CD44_cells_in_drug_tolerant_Du145_cell_cultures_/406551", "title"=>"Molecular changes and reduced CD44<sup>+</sup> cells in drug-tolerant Du145 cell cultures.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-15 01:49:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/736351"], "description"=>"<p>A–C. CD44 knockdown experiments. Du145 cells infected with the control (NS) or CD44 shRNA lentivectors (MOI 20; 72 h) were plated (10,000/well) in triplicate, pulsed by BrdU for 4 h, and processed for BrdU staining (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024397#s2\" target=\"_blank\">Materials & Methods</a>). Shown in (A) is the quantification of BrdU<sup>+</sup> cells from a total of 500 cells counted for each and in (B) are representative images (×400). Inset, Western blot showing reduced CD44 protein expression in Du145 cells infected with CD44-shRNA (lane 2) compared with the cells infected with NS-shRNA (lane 1). For experiments in C, Du145 cells infected with the control (NS) or CD44 lentivector were plated (5,000/well) in quadruplicate on day 0. At the end of day 2, 4, 6, and 8, cells were dissociated and counted by Trypan blue exclusion. Plotted are the live cell numbers (mean ± SD) as a function of time. *<i>P</i> = 0.019; **<i>P</i> = 0.003 (Student's <i>t</i>-test). D–F. CD44 overexpression experiments. Du145-VP16 cells infected with GFP or CD44 retroviral vectors (MOI 20; 72 h) were plated (10,000/well) in triplicate, pulsed by BrdU for 4 h, and processed for BrdU staining. Shown in (D) is the quantification of BrdU<sup>+</sup> cells from a total of 500 cells counted for each condition and in (E) are representative images (×400). Inset, Western blot showing increased CD44 protein expression in Du145-VP16 cells infected with pBabe-CD44 (lane 2) compared with the cells infected with pBabe-GFP (lane 1). For experiments in F, Du145-VP16 cells infected with the GFP or CD44 retroviral vectors were plated (5,000/well) in quadruplicate on day 0. At the end of day 2, 4, 6, and 8, cells were dissociated and counted by Trypan blue exclusion. Plotted are the live cell numbers (mean ± SD) as a function of time. *P = 0.035; **P = 0.028. G–H. Paclitaxel inhibits PC3 orthotopic tumor growth (G) and metastasis (H). Presented in (G) is the tumor weight (mean ± S.D; n = 5 for each group). Tumor incidence is the same (i.e., 5/5) for both groups. Shown in (H) are representative phase and GFP microphotographs of lung metastases, i.e., GFP<sup>+</sup> foci.</p>", "links"=>[], "tags"=>["knockdown", "overexpression", "du145", "cells", "inhibits"], "article_id"=>406686, "categories"=>["Cancer", "Cell Biology", "Genetics"], "users"=>["Hong Yan", "Xin Chen", "Qiuping Zhang", "Jichao Qin", "Hangwen Li", "Can Liu", "Tammy Calhoun-Davis", "Luis Della Coletta", "Jim Klostergaard", "Izabela Fokt", "Stanislaw Skora", "Waldemar Priebe", "Yongyi Bi", "Dean G. Tang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0024397.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CD44_knockdown_and_overexpression_in_Du145_cells_inhibits_and_promotes_respectively_cell_proliferation_/406686", "title"=>"CD44 knockdown and overexpression in Du145 cells inhibits and promotes, respectively, cell proliferation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-15 01:51:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/736460"], "description"=>"<p>A. Du145-VP16 cells show both decreases and increases in stemness gene expression levels. The mRNA levels of the indicated genes in parental Du145 (set at 1, blue bars) and Du145-VP16 (red bars) cells were determined by qPCR. P values were indicated for those genes that showed statistically significant differences. B. Tumor incidence in various types of Du145-VP16 cells implanted (10,000) in NOD/SCID mice. As shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024397#pone-0024397-t001\" target=\"_blank\">Table 1</a>, parental Du145 cells showed 100% incidence at 10,000 cells whereas Du145-VP16 cells failed to initiate tumors. When cultured in drug-free (DF) medium for 2 and 3 months, increased tumor incidence was observed (**<i>P</i><0.01 compared with Du145-VP16). When Du145-VP16 cells treated with Aza (0.1 µM, 72 h) were injected, increased tumor incidence was also observed (*P<0.05 when compared with Du145-VP16 cells). C–D. Du145-VP16 cells treated with the indicated chemicals (72 h) were used in Western blotting analysis of CD44, KDM5A, and E-cadherin. β-Actin was used as loading control.</p>", "links"=>[], "tags"=>["profiles", "epigenetic", "mechanisms", "du145-vp16"], "article_id"=>406801, "categories"=>["Cancer", "Cell Biology", "Genetics"], "users"=>["Hong Yan", "Xin Chen", "Qiuping Zhang", "Jichao Qin", "Hangwen Li", "Can Liu", "Tammy Calhoun-Davis", "Luis Della Coletta", "Jim Klostergaard", "Izabela Fokt", "Stanislaw Skora", "Waldemar Priebe", "Yongyi Bi", "Dean G. Tang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0024397.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_8216_Stemness_8217_gene_expression_profiles_and_epigenetic_mechanisms_in_Du145_VP16_cells_/406801", "title"=>"‘Stemness’ gene expression profiles and epigenetic mechanisms in Du145-VP16 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-09-15 01:53:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/736558"], "description"=>"a<p>Parental Du145 or drug-tolerant Du145 cells were s.c implanted in 50% Matrigel, at the numbers indicated, in NOD/SCID mice. In the two experiments marked by #, cells were first cultured in drug-free medium for 2 months prior to injections.</p>b<p>Tumor incidence (% of tumor development/injections).</p>c<p>Tumor-initiating frequency, as determined using the L-Calc™ software (Stemcell Technologies). The ranges were indicated in the parentheses.</p>d<p>Tumor latency (mean time in days from injection to when tumors were first palpated) and termination time (days from injection to when animals were sacrificed).</p>e<p>Mean ± S.D (ranges in parentheses). Note that tumor weights sometimes varied greatly among different cell number groups. For statistical analyses, Fisher's Exact Test was used to compare tumor incidence and Student <i>t</i>-test was used to compare tumor weights and latencies.</p><p>*P<0.05;</p><p>**P<0.01, when compared with the parental Du145 cells of the same number.</p>", "links"=>[], "tags"=>["du145", "cells", "reduced", "tumorigenic"], "article_id"=>406899, "categories"=>["Cancer", "Cell Biology", "Genetics"], "users"=>["Hong Yan", "Xin Chen", "Qiuping Zhang", "Jichao Qin", "Hangwen Li", "Can Liu", "Tammy Calhoun-Davis", "Luis Della Coletta", "Jim Klostergaard", "Izabela Fokt", "Stanislaw Skora", "Waldemar Priebe", "Yongyi Bi", "Dean G. Tang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0024397.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Drug_tolerant_Du145_cells_possess_much_reduced_tumorigenic_potential_/406899", "title"=>"Drug-tolerant Du145 cells possess much reduced tumorigenic potential.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-09-15 01:54:59"}

PMC Usage Stats | Further Information

  • {"scanned-page-browse"=>"0", "month"=>"9", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"101", "unique-ip"=>"85", "pdf"=>"69", "year"=>"2011", "figure"=>"14", "scanned-summary"=>"0", "supp-data"=>"2"}
  • {"month"=>"10", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"132", "year"=>"2011", "pdf"=>"80", "unique-ip"=>"125", "figure"=>"37", "scanned-summary"=>"0", "supp-data"=>"2"}
  • {"scanned-page-browse"=>"0", "month"=>"11", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"65", "unique-ip"=>"55", "pdf"=>"65", "year"=>"2011", "figure"=>"13", "scanned-summary"=>"0", "supp-data"=>"1"}
  • {"month"=>"12", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"55", "year"=>"2011", "pdf"=>"49", "unique-ip"=>"63", "figure"=>"16", "scanned-summary"=>"0", "supp-data"=>"2"}
  • {"scanned-page-browse"=>"0", "month"=>"1", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"38", "unique-ip"=>"38", "pdf"=>"28", "year"=>"2012", "figure"=>"10", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"2", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"47", "year"=>"2012", "pdf"=>"23", "unique-ip"=>"43", "figure"=>"5", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"3", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"55", "unique-ip"=>"49", "pdf"=>"37", "year"=>"2012", "figure"=>"7", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"4", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"50", "year"=>"2012", "pdf"=>"34", "unique-ip"=>"49", "figure"=>"6", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"5", "cited-by"=>"0", "abstract"=>"5", "full-text"=>"48", "unique-ip"=>"51", "pdf"=>"39", "year"=>"2012", "figure"=>"12", "scanned-summary"=>"0", "supp-data"=>"2"}
  • {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"44", "year"=>"2012", "pdf"=>"28", "unique-ip"=>"49", "figure"=>"3", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"unique-ip"=>"18", "full-text"=>"22", "pdf"=>"17", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"7"}
  • {"unique-ip"=>"30", "full-text"=>"38", "pdf"=>"18", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"17", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"8"}
  • {"unique-ip"=>"17", "full-text"=>"17", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"9"}
  • {"unique-ip"=>"14", "full-text"=>"17", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"10"}
  • {"unique-ip"=>"11", "full-text"=>"14", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"12"}
  • {"unique-ip"=>"31", "full-text"=>"33", "pdf"=>"16", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"1"}
  • {"unique-ip"=>"19", "full-text"=>"20", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
  • {"unique-ip"=>"18", "full-text"=>"17", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"2"}
  • {"unique-ip"=>"14", "full-text"=>"14", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
  • {"unique-ip"=>"22", "full-text"=>"24", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"11"}
  • {"unique-ip"=>"18", "full-text"=>"16", "pdf"=>"7", "abstract"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
  • {"unique-ip"=>"25", "full-text"=>"33", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"21", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
  • {"unique-ip"=>"19", "full-text"=>"17", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"4", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
  • {"unique-ip"=>"13", "full-text"=>"8", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
  • {"unique-ip"=>"14", "full-text"=>"13", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
  • {"unique-ip"=>"10", "full-text"=>"12", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
  • {"unique-ip"=>"10", "full-text"=>"5", "pdf"=>"5", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"unique-ip"=>"16", "full-text"=>"13", "pdf"=>"7", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"7", "full-text"=>"5", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"7", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"18", "full-text"=>"18", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"16", "full-text"=>"15", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"8", "full-text"=>"4", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"4", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"11", "full-text"=>"8", "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"=>"8", "full-text"=>"5", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"13", "full-text"=>"7", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"28", "full-text"=>"25", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"3", "cited-by"=>"2", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"11", "full-text"=>"13", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"19", "full-text"=>"11", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"9", "full-text"=>"13", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"7", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"3", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"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"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"4", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"18", "full-text"=>"25", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"4", "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"=>"5"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}

Relative Metric

{"start_date"=>"2011-01-01T00:00:00Z", "end_date"=>"2011-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[304, 568, 702, 818, 927, 1027, 1118, 1206, 1285, 1357, 1427, 1500, 1564, 1636, 1705, 1773, 1840, 1909, 1974, 2039, 2106, 2170, 2234, 2296, 2358, 2423, 2484, 2546, 2606, 2673, 2734, 2795, 2857, 2921, 2984, 3046, 3100]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[308, 576, 718, 839, 960, 1061, 1156, 1249, 1331, 1408, 1484, 1558, 1625, 1698, 1767, 1842, 1912, 1990, 2058, 2128, 2183, 2259, 2317, 2378, 2436, 2488, 2552, 2627, 2692, 2759, 2820, 2881, 2940, 3001, 3061, 3117, 3164]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[303, 571, 709, 823, 937, 1038, 1133, 1216, 1298, 1370, 1447, 1518, 1588, 1656, 1725, 1790, 1856, 1926, 1992, 2054, 2118, 2182, 2242, 2301, 2363, 2425, 2484, 2544, 2602, 2662, 2716, 2776, 2841, 2901, 2960, 3016, 3071]}, {"subject_area"=>"/Medicine and health sciences/Pharmacology", "average_usage"=>[337, 604, 750, 875, 1001, 1107, 1205, 1299, 1391, 1468, 1552, 1629, 1709, 1785, 1862, 1935, 2013, 2081, 2140, 2212, 2281, 2352, 2422, 2489, 2564, 2629, 2698, 2752, 2833, 2880, 2925, 2983, 3042, 3111, 3183, 3250, 3311]}]}
Loading … Spinner
There are currently no alerts