CiteULike

Mendeley | Further Information

{"title"=>"Sphere Culture of Murine Lung Cancer Cell Lines Are Enriched with Cancer Initiating Cells", "type"=>"journal", "authors"=>[{"first_name"=>"Brian J.", "last_name"=>"Morrison", "scopus_author_id"=>"7101794431"}, {"first_name"=>"Jason C.", "last_name"=>"Steel", "scopus_author_id"=>"8333640600"}, {"first_name"=>"John C.", "last_name"=>"Morris", "scopus_author_id"=>"35355376000"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84869015742", "sgr"=>"84869015742", "pui"=>"366043234", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)", "pmid"=>"23152931", "doi"=>"10.1371/journal.pone.0049752"}, "id"=>"a3431d9c-645b-31f6-ae68-36ac262234ba", "abstract"=>"Cancer initiating cells (CICs) represent a unique cell population essential for the maintenance and growth of tumors. Most in vivo studies of CICs utilize human tumor xenografts in immunodeficient mice. These models provide limited information on the interaction of CICs with the host immune system and are of limited value in assessing therapies targeting CICs, especially immune-based therapies. To assess this, a syngeneic cancer model is needed. We examined the sphere-forming capacity of thirteen murine lung cancer cell lines and identified TC-1 and a metastatic subclone of Lewis lung carcinoma (HM-LLC) as cell lines that readily formed and maintained spheres over multiple passages. TC-1 tumorspheres were not enriched for expression of CD133 or CD44, putative CIC markers, nor did they demonstrate Hoechst 33342 side population staining or Aldefluor activity compared to adherent TC-1 cells. However, in tumorsphere culture, these cells exhibited self-renewal and long-term symmetric division capacity and expressed more Oct-4 compared to adherent cells. HM-LLC sphere-derived cells exhibited increased Oct-4, CD133, and CD44 expression, demonstrated a Hoechst 33342 side population and Aldefluor activity compared to adherent cells or a low metastatic subclone of LLC (LM-LLC). In syngeneic mice, HM-LLC sphere-derived cells required fewer cells to initiate tumorigenesis compared to adherent or LM-LLC cells. Similarly TC-1 sphere-derived cells were more tumorigenic than adherent cells in syngeneic mice. In contrast, in immunocompromised mice, less than 500 sphere or adherent TC-1 cells and less than 1,000 sphere or adherent LLC cells were required to initiate a tumor. We suggest that no single phenotypic marker can identify CICs in murine lung cancer cell lines. Tumorsphere culture may provide an alternative approach to identify and enrich for murine lung CICs. Furthermore, we propose that assessing tumorigenicity of murine lung CICs in syngeneic mice better models the interaction of CICs with the host immune system.", "link"=>"http://www.mendeley.com/research/sphere-culture-murine-lung-cancer-cell-lines-enriched-cancer-initiating-cells", "reader_count"=>40, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>8, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>14, "Student > Master"=>5, "Other"=>3, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>8, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>14, "Student > Master"=>5, "Other"=>3, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>6, "Medicine and Dentistry"=>11, "Agricultural and Biological Sciences"=>20, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>11}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>20}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Portugal"=>1, "Switzerland"=>1}, "group_count"=>0}

ORCID | Further Information

CrossRef

• http://doi.org/10.1016/j.omtn.2018.08.016
• http://doi.org/10.4252/wjsc.v9.i9.159
• http://doi.org/10.1038/s41388-018-0228-x
• http://doi.org/10.1186/s13045-016-0307-9
• http://doi.org/10.1002/cam4.291
• http://doi.org/10.3390/jfb6020241
• http://doi.org/10.1039/C3LC51093J
• http://doi.org/10.3389/fonc.2019.00153
• http://doi.org/10.1371/journal.pone.0095157
• http://doi.org/10.1177/1534735414534462
• http://doi.org/10.1038/labinvest.2015.48
• http://doi.org/10.1371/journal.pcbi.1005093
• http://doi.org/10.1016/j.yexcr.2016.06.003
• http://doi.org/10.1074/jbc.M114.624965
• http://doi.org/10.1016/j.lungcan.2015.11.013
• http://doi.org/10.1016/j.bbrc.2016.10.057
• http://doi.org/10.1186/s12885-018-4389-3
• http://doi.org/10.2217/fon.13.38
• http://doi.org/10.1007/s11523-012-0247-4
• http://doi.org/10.1111/cas.12475
• http://doi.org/10.1093/sleep/zsw040

DataCite

Europe PMC Citations | Further Information

Europe PMC Database Citations

PubMed Central

• 3763165
• 3986414
• 4423515
• 4075950
• 4322977
• 4694990
• 4302662
• 4493510
• 4462388

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84869015742"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84869015742?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84869015742&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84869015742&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84869015742", "dc:identifier"=>"SCOPUS_ID:84869015742", "eid"=>"2-s2.0-84869015742", "dc:title"=>"Sphere Culture of Murine Lung Cancer Cell Lines Are Enriched with Cancer Initiating Cells", "dc:creator"=>"Morrison B.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"7", "prism:issueIdentifier"=>"11", "prism:pageRange"=>nil, "prism:coverDate"=>"2012-11-13", "prism:coverDisplayDate"=>"13 November 2012", "prism:doi"=>"10.1371/journal.pone.0049752", "citedby-count"=>"30", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"University of Cincinnati", "affiliation-city"=>"Cincinnati", "affiliation-country"=>"United States"}], "pubmed-id"=>"23152931", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e49752", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Web of Science® | Further Information

Article Coverage

Article Coverage Curated

Facebook

• {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0049752", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Journal Comments | Further Information

• {"type"=>"COMMENT", "annotationUri"=>"info:doi/10.1371/annotation/715664e3-a13c-4318-9cb1-62a86abfedbe", "title"=>"Media Coverage of This Article", "body"=>"The following article represents some of the media coverage that has occurred for this paper:\n\nPublication: University of Cincinnati \nTitle: “UC HealthNews : Stem Cell Finding Could Advance Immunotherapy for Lung Cancer”\nhttp://www.healthnews.uc.edu/news/?/21324/\n\nIf you see any additional coverage of this paper in the press or blogosphere, please reply to this thread and add the link to the article. \n", "isRemoved"=>false, "created"=>"2012-11-17T00:37:52Z", "lastModified"=>"2012-11-17T00:37:52Z", "creator"=>{"userId"=>"80539"}, "highlightedText"=>"", "competingInterestStatement"=>{"creatorWasPrompted"=>true, "hasCompetingInterests"=>true, "body"=>"PLOS ONE Staff"}, "parentArticle"=>{"doi"=>"info:doi/10.1371/journal.pone.0049752", "state"=>"published", "journals"=>{"PLoSONE"=>{"journalKey"=>"PLoSONE", "eIssn"=>"1932-6203", "title"=>"PLOS ONE"}}}, "replyTreeSize"=>0, "mostRecentActivity"=>"2012-11-17T00:37:52Z", "replies"=>[]}

Nature

Reddit

Research Blogging

ScienceSeeker | Further Information

Twitter

• {"id"=>"268475657586098177", "text"=>"Sphere Culture of Murine Lung Cancer Cell Lines Are Enriched with Cancer Initiating Cells http://t.co/gh1JyO4X", "created_at"=>"2012-11-13T22:09:19Z", "user"=>"TestCellBio", "user_name"=>"Test", "user_profile_image"=>"http://a0.twimg.com/sticky/default_profile_images/default_profile_6_normal.png"}
• {"id"=>"268523258603773952", "text"=>"Interaction model of CICs w/ host immune system: Sphere culture of murine lung #ca c's enriched w/ CA initiating c's http://t.co/RiHw8FA2", "created_at"=>"2012-11-14T01:18:28Z", "user"=>"BiomedRevon", "user_name"=>"Mirko ", "user_profile_image"=>"http://a0.twimg.com/profile_images/1518893315/Arcimboldo_Librarian_Stokholm_normal.jpg"}
• {"id"=>"268748601147133953", "text"=>"Cancer stem cells: Sphere Culture of Murine Lung Cancer Cell Lines Are Enriched with Cancer Initiating Cells, PLoSOne http://t.co/e4nvnLyB", "created_at"=>"2012-11-14T16:13:54Z", "user"=>"NYUBiotech", "user_name"=>"NYU Biotech", "user_profile_image"=>"http://a0.twimg.com/profile_images/2819468759/3e406934c6d965918da400c107c06089_normal.png"}
• {"id"=>"948878965489438721", "text"=>"#PLOSONE: Sphere Culture of Murine Lung Cancer Cell Lines Are Enriched with Cancer Initiating Cells https://t.co/iDzS0mypCf", "created_at"=>"2018-01-04T11:29:09Z", "user"=>"muc1_galectin3", "user_name"=>"Brian", "user_profile_image"=>"http://pbs.twimg.com/profile_images/948876465654910976/3fJNP8f3_normal.jpg"}

Wikipedia

Wordpress.com | Further Information

Counter

• {"month"=>"11", "year"=>"2012", "pdf_views"=>"172", "xml_views"=>"11", "html_views"=>"709"}
• {"month"=>"12", "year"=>"2012", "pdf_views"=>"78", "xml_views"=>"4", "html_views"=>"220"}
• {"month"=>"1", "year"=>"2013", "pdf_views"=>"61", "xml_views"=>"0", "html_views"=>"250"}
• {"month"=>"2", "year"=>"2013", "pdf_views"=>"39", "xml_views"=>"1", "html_views"=>"176"}
• {"month"=>"3", "year"=>"2013", "pdf_views"=>"58", "xml_views"=>"1", "html_views"=>"219"}
• {"month"=>"4", "year"=>"2013", "pdf_views"=>"39", "xml_views"=>"2", "html_views"=>"191"}
• {"month"=>"5", "year"=>"2013", "pdf_views"=>"45", "xml_views"=>"0", "html_views"=>"224"}
• {"month"=>"6", "year"=>"2013", "pdf_views"=>"44", "xml_views"=>"0", "html_views"=>"194"}
• {"month"=>"7", "year"=>"2013", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"167"}
• {"month"=>"8", "year"=>"2013", "pdf_views"=>"29", "xml_views"=>"0", "html_views"=>"139"}
• {"month"=>"9", "year"=>"2013", "pdf_views"=>"31", "xml_views"=>"1", "html_views"=>"121"}
• {"month"=>"10", "year"=>"2013", "pdf_views"=>"33", "xml_views"=>"2", "html_views"=>"142"}
• {"month"=>"11", "year"=>"2013", "pdf_views"=>"31", "xml_views"=>"0", "html_views"=>"132"}
• {"month"=>"12", "year"=>"2013", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"93"}
• {"month"=>"1", "year"=>"2014", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"111"}
• {"month"=>"2", "year"=>"2014", "pdf_views"=>"35", "xml_views"=>"2", "html_views"=>"85"}
• {"month"=>"3", "year"=>"2014", "pdf_views"=>"19", "xml_views"=>"2", "html_views"=>"81"}
• {"month"=>"4", "year"=>"2014", "pdf_views"=>"21", "xml_views"=>"1", "html_views"=>"110"}
• {"month"=>"5", "year"=>"2014", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"82"}
• {"month"=>"6", "year"=>"2014", "pdf_views"=>"13", "xml_views"=>"1", "html_views"=>"71"}
• {"month"=>"7", "year"=>"2014", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"92"}
• {"month"=>"8", "year"=>"2014", "pdf_views"=>"13", "xml_views"=>"2", "html_views"=>"59"}
• {"month"=>"9", "year"=>"2014", "pdf_views"=>"19", "xml_views"=>"1", "html_views"=>"118"}
• {"month"=>"10", "year"=>"2014", "pdf_views"=>"15", "xml_views"=>"1", "html_views"=>"73"}
• {"month"=>"11", "year"=>"2014", "pdf_views"=>"24", "xml_views"=>"1", "html_views"=>"88"}
• {"month"=>"12", "year"=>"2014", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"44"}
• {"month"=>"1", "year"=>"2015", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"54"}
• {"month"=>"2", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"24"}
• {"month"=>"3", "year"=>"2015", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"75"}
• {"month"=>"4", "year"=>"2015", "pdf_views"=>"14", "xml_views"=>"1", "html_views"=>"89"}
• {"month"=>"5", "year"=>"2015", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"54"}
• {"month"=>"6", "year"=>"2015", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"63"}
• {"month"=>"7", "year"=>"2015", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"51"}
• {"month"=>"8", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"45"}
• {"month"=>"9", "year"=>"2015", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"65"}
• {"month"=>"10", "year"=>"2015", "pdf_views"=>"14", "xml_views"=>"1", "html_views"=>"45"}
• {"month"=>"11", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"41"}
• {"month"=>"12", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"58"}
• {"month"=>"1", "year"=>"2016", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"44"}
• {"month"=>"2", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"41"}
• {"month"=>"3", "year"=>"2016", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"46"}
• {"month"=>"4", "year"=>"2016", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"62"}
• {"month"=>"5", "year"=>"2016", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"70"}
• {"month"=>"6", "year"=>"2016", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"38"}
• {"month"=>"7", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"29"}
• {"month"=>"8", "year"=>"2016", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"48"}
• {"month"=>"9", "year"=>"2016", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"61"}
• {"month"=>"10", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"41"}
• {"month"=>"11", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"63"}
• {"month"=>"12", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"64"}
• {"month"=>"1", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"48"}
• {"month"=>"2", "year"=>"2017", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"73"}
• {"month"=>"3", "year"=>"2017", "pdf_views"=>"13", "xml_views"=>"1", "html_views"=>"72"}
• {"month"=>"4", "year"=>"2017", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"61"}
• {"month"=>"5", "year"=>"2017", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"49"}
• {"month"=>"6", "year"=>"2017", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"73"}
• {"month"=>"7", "year"=>"2017", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"59"}
• {"month"=>"8", "year"=>"2017", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"51"}
• {"month"=>"9", "year"=>"2017", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"49"}
• {"month"=>"10", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"54"}
• {"month"=>"11", "year"=>"2017", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"78"}
• {"month"=>"12", "year"=>"2017", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"50"}
• {"month"=>"1", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"78"}
• {"month"=>"2", "year"=>"2018", "pdf_views"=>"15", "xml_views"=>"1", "html_views"=>"50"}
• {"month"=>"3", "year"=>"2018", "pdf_views"=>"3", "xml_views"=>"1", "html_views"=>"28"}
• {"month"=>"4", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"27"}
• {"month"=>"5", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"18"}
• {"month"=>"6", "year"=>"2018", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"24"}
• {"month"=>"7", "year"=>"2018", "pdf_views"=>"2", "xml_views"=>"3", "html_views"=>"28"}
• {"month"=>"8", "year"=>"2018", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"22"}
• {"month"=>"9", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"29"}
• {"month"=>"10", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"2", "html_views"=>"24"}
• {"month"=>"11", "year"=>"2018", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"35"}
• {"month"=>"12", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"2", "html_views"=>"32"}
• {"month"=>"1", "year"=>"2019", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"31"}
• {"month"=>"2", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"2", "html_views"=>"22"}
• {"month"=>"3", "year"=>"2019", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"29"}
• {"month"=>"4", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"20"}
• {"month"=>"5", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"17"}
• {"month"=>"6", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"18"}
• {"month"=>"7", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"10"}
• {"month"=>"8", "year"=>"2019", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"14"}
• {"month"=>"9", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"13"}
• {"month"=>"10", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"16"}
• {"month"=>"11", "year"=>"2019", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"18"}
• {"month"=>"12", "year"=>"2019", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"5"}

Figshare

• {"files"=>["https://ndownloader.figshare.com/files/544259"], "description"=>"<p>Representative SP plots for (<b>A</b>) LLC cells and (<b>B</b>) TC-1 cells comparing matched adherent cells to passage 2, day 1 and day 7 sphere-derived cells. Hoechst 33342 staining was confirmed with verapamil blockade. (<b>C</b>) SP frequency was significantly increased in HM-LLC spheres compared to adherent cells; *P<0.001; **P≤0.012. HM-LLC and LM-LLC adherent cells were not significantly different for SP frequency. (<b>D</b>) SP was not found to be upregulated in sphere-derived TC-1 cells compared to matched adherent cells. Day 1 sphere-derived cells had a significantly lower frequency of SP cells compared to adherent cells and day 7 sphere-derived cells; *P = 0.03. Plots represent combined data from three biological replicates with three technical replicates each. Bars: ±SEM.</p>", "links"=>[], "tags"=>["33342", "enhanced", "hm-llc", "tc-1", "spheres", "compared", "adherent"], "article_id"=>214750, "categories"=>["Cancer", "Cell Biology"], "users"=>["Brian J. Morrison", "Jason C. Steel", "John C. Morris"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049752.g004", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hoechst_33342_side_population_SP_expression_is_enhanced_in_HM_LLC_but_not_in_TC_1_spheres_compared_to_adherent_cells_/214750", "title"=>"Hoechst 33342 side population (SP) expression is enhanced in HM-LLC but not in TC-1 spheres compared to adherent cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:25:26"}
• {"files"=>["https://ndownloader.figshare.com/files/544113"], "description"=>"<p>(<b>A–B</b>) Representative plots showing Aldefluor staining (blue) and DEAB control staining (red) for HM-LLC, LM-LLC and TC-1 adherent cells compared to passage 2, day 1 and day 7 sphere-derived cells. Aldefluor high expressing cells (rectangular box) are significantly greater in (<b>C</b>) frequency and (<b>D</b>) mean fluorescent intensity (MFI) of Aldefluor within HM-LLC spheres compared to LM-LLC or HM-LLC adherent cells, and HM-LLC adherent cells express more Aldefluor than LM-LLC adherent cells; frequency (<b>C</b>) *P≤0.001; MFI (<b>D</b>) *P≤0.002. Compared to DEAB staining, Aldefluor positivity (non-rectangular box) was found to be significantly higher in TC-1 adherent cells compared to spheres (<b>E</b>); *P≤0.004. MFI of Aldefluor within the TC-1 groups (<b>F</b>) was not found to be significantly different. No Aldefluor high population was noted for TC-1 spheres or adherent cells. Plots represent combined data from two biological repeats with three technical replicates each. Bars: ±SEM.</p>", "links"=>[], "tags"=>["enhanced", "hm-llc", "tc-1", "spheres", "compared", "adherent"], "article_id"=>214604, "categories"=>["Cancer", "Cell Biology"], "users"=>["Brian J. Morrison", "Jason C. Steel", "John C. Morris"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049752.g003", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Aldefluor_expression_is_enhanced_in_HM_LLC_but_not_in_TC_1_spheres_compared_to_adherent_cells_/214604", "title"=>"Aldefluor expression is enhanced in HM-LLC but not in TC-1 spheres compared to adherent cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:24:36"}
• {"files"=>["https://ndownloader.figshare.com/files/544512"], "description"=>"<p>Confidence interval plot of limiting dilution analysis is shown with the y-axis displaying the estimated frequency of cancer initiating cells (CIC). (<b>A</b>) A limiting dilution of TC-1 cells (120,000, 80,000, 40,000, 10,000, 5,000, and 1,000) were injected subcutaneously into syngeneic C57BL/6 mice (n = 4 to 8). Sphere derived cells were found to be more tumorigenic than adherent cells; *P≤0.001; **P<0.02. Day 1 sphere-derived cells were more tumorigenic than day 7; ***P = 0.04. A limiting dilution (10,000, 1,000, and 500 cells) (n = 6 to 8) of the same three groups were injected into NSG mice and CIC frequency was found to be below 1/500 for all groups. (<b>B</b>) Analysis of LLC limiting dilution tumor experiment for syngeneic (80,000, 40,000, 20,000, and 10,000 cells) and immunocompromised (NSG) mice (80,000, 40,000, 10,000, and 1,000 cells) (n = 4 to 9). No significant differences noted; however, sphere-derived cells trended towards being more tumorigenic than HM or LM adherent cells in C57BL/6 mice. Lower numbers of implanted cells were needed to initiate tumors in immunocompromised animals than in syngeneic animals with the estimated CIC frequency below 1/1000 for all LLC groups.</p>", "links"=>[], "tags"=>["tumorigenicity", "tc-1", "llc", "cells", "immunocompetent", "immunodeficient"], "article_id"=>215002, "categories"=>["Cancer", "Cell Biology"], "users"=>["Brian J. Morrison", "Jason C. Steel", "John C. Morris"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049752.g006", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vivo_tumorigenicity_of_TC_1_and_LLC_cells_in_immunocompetent_and_immunodeficient_mice_/215002", "title"=>"<i>In vivo</i> tumorigenicity of TC-1 and LLC cells in immunocompetent and immunodeficient mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:26:55"}
• {"files"=>["https://ndownloader.figshare.com/files/544584"], "description"=>"*<p>Ability to form three-dimensional multicellular spheroids.</p>†<p>Mean fold expansion over 1 for serial passage, and ability to passage as spheres more than 3 passages.</p>§<p>Fold expansion average ±standard deviation.</p>", "links"=>[], "tags"=>["cancer", "lines", "forming"], "article_id"=>215079, "categories"=>["Cancer", "Cell Biology"], "users"=>["Brian J. Morrison", "Jason C. Steel", "John C. Morris"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049752.t001", "stats"=>{"downloads"=>2, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Murine_lung_cancer_cell_lines_sphere_forming_capacity_/215079", "title"=>"Murine lung cancer cell lines sphere forming capacity.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 20:27:20"}
• {"files"=>["https://ndownloader.figshare.com/files/544020"], "description"=>"<p>Real time PCR quantitation was done for Oct-4, a gene associated with stem cell self-renewal, mRNA expression. TC-1 spheres (<b>A</b>) and HM-LLC spheres (<b>B</b>) demonstrate increased Oct-4 expression compared to matched adherent cells; *P≤0.001. HM-LLC cells expressed significantly more Oct-4 than LM-LLC adherent cells; **P = 0.005. Plots represent combined data from 2–4 biological replicates, each with three technical replicates. TC-1 cells (red); LM-LLC adherent (grey); HM-LLC cells (black). Bars: ±SEM.</p>", "links"=>[], "tags"=>["spheres", "compared", "adherent"], "article_id"=>214516, "categories"=>["Cancer", "Cell Biology"], "users"=>["Brian J. Morrison", "Jason C. Steel", "John C. Morris"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049752.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Oct_4_expression_is_increased_in_spheres_compared_to_adherent_cells_/214516", "title"=>"Oct-4 expression is increased in spheres compared to adherent cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:24:06"}
• {"files"=>["https://ndownloader.figshare.com/files/543933"], "description"=>"<p>Photomicrographs (10X) of passage 2 day 7 sphere cultures of (<b>A</b>) TC-1 spheres, (<b>B</b>) HM-LLC spheres and (<b>C</b>) LM-LLC sphere media culture. Bar = 100 µm. (<b>D</b>) Total fold expansion and (<b>E</b>) symmetric division frequency over eight passages for TC-1 spheres (red) and HM-LLC spheres (black), and two passages for LM-LLC sphere media culture (grey) shows significant differences; *P<0.001. (<b>F–G</b>) Fold expansion over seven passages for TC-1 spheres (red) and HM-LLC spheres (black). (<b>H</b>) Passage 2 spheres were cultured and counted for total number of cells on the days as shown. Experiment repeated twice, representative results shown. On day 1 the total number of cells in culture is reduced. The surviving mitogen-responsive cancer initiating cells are responsible for cell proliferation and generating fresh multi-cellular spheres that can be harvested on day 7. Bars: ±Standard error of the mean (SEM).</p>", "links"=>[], "tags"=>["tumorsphere"], "article_id"=>214428, "categories"=>["Cancer", "Cell Biology"], "users"=>["Brian J. Morrison", "Jason C. Steel", "John C. Morris"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049752.g001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vitro_tumorsphere_assays_/214428", "title"=>"<i>In vitro</i> tumorsphere assays.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:23:32"}
• {"files"=>["https://ndownloader.figshare.com/files/544362"], "description"=>"<p>(<b>A</b>) Representative flow cytometry plots for CD133 (Y-axis) and CD44 (X-axis) co-staining. (<b>B and D</b>) The mean fluorescent intensity (MFI) of CD44 is shown corrected for intensity of isotype staining for LLC and TC-1 cells. (<b>B</b>) HM-LLC spheres and adherent cells as well as LLC (ATCC) cells express higher amounts of CD44 compared to LM-LLC cells. Sphere-derived cells were found to have a lower MFI for CD44 compared to HM-LLC adherent cells. D7 sphere-derived cells had a lower MFI for CD44 compared to D1 cells; *P<0.001. <b>(D</b>) Day 1 TC-1 sphere-derived cells express less CD44 than day 7 or adherent cells; *P≤0.002. (<b>C</b>) CD133 frequency of positive cells is higher in HM-LLC spheres compared to LM-LLC adherent cells; *P≤0.043. CD133 expression was not significantly different between HM-LLC adherent cells and spheres or amongst the three different LLC adherent cells. (<b>E</b>) No significant difference in CD133 expression amongst the TC-1 culture conditions. Experiment done in triplicate, representative results shown. Bars: ±SEM.</p>", "links"=>[], "tags"=>["cell biology", "oncology"], "article_id"=>214858, "categories"=>["Cancer", "Cell Biology"], "users"=>["Brian J. Morrison", "Jason C. Steel", "John C. Morris"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0049752.g005", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CD133_CD44_cell_surface_expression_/214858", "title"=>"CD133/CD44 cell surface expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:26:06"}

PMC Usage Stats | Further Information

• {"unique-ip"=>"40", "full-text"=>"39", "pdf"=>"20", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"12"}
• {"unique-ip"=>"50", "full-text"=>"49", "pdf"=>"17", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"1"}
• {"unique-ip"=>"30", "full-text"=>"32", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
• {"unique-ip"=>"21", "full-text"=>"24", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"2"}
• {"unique-ip"=>"26", "full-text"=>"28", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
• {"unique-ip"=>"25", "full-text"=>"26", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"17", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"11"}
• {"unique-ip"=>"31", "full-text"=>"34", "pdf"=>"15", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"17", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
• {"unique-ip"=>"31", "full-text"=>"27", "pdf"=>"18", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
• {"unique-ip"=>"10", "full-text"=>"6", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
• {"unique-ip"=>"20", "full-text"=>"14", "pdf"=>"12", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
• {"unique-ip"=>"18", "full-text"=>"23", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
• {"unique-ip"=>"17", "full-text"=>"14", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
• {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
• {"unique-ip"=>"14", "full-text"=>"12", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
• {"unique-ip"=>"21", "full-text"=>"19", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"17", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
• {"unique-ip"=>"19", "full-text"=>"20", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
• {"unique-ip"=>"15", "full-text"=>"13", "pdf"=>"10", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
• {"unique-ip"=>"7", "full-text"=>"13", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
• {"unique-ip"=>"15", "full-text"=>"16", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
• {"unique-ip"=>"19", "full-text"=>"15", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
• {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
• {"unique-ip"=>"27", "full-text"=>"27", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
• {"unique-ip"=>"20", "full-text"=>"19", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
• {"unique-ip"=>"15", "full-text"=>"18", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
• {"unique-ip"=>"24", "full-text"=>"27", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
• {"unique-ip"=>"18", "full-text"=>"15", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
• {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
• {"unique-ip"=>"30", "full-text"=>"29", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"9"}
• {"unique-ip"=>"18", "full-text"=>"21", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"10"}
• {"unique-ip"=>"17", "full-text"=>"18", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
• {"unique-ip"=>"17", "full-text"=>"13", "pdf"=>"9", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
• {"unique-ip"=>"32", "full-text"=>"31", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
• {"unique-ip"=>"10", "full-text"=>"6", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
• {"unique-ip"=>"28", "full-text"=>"27", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
• {"unique-ip"=>"20", "full-text"=>"17", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
• {"unique-ip"=>"17", "full-text"=>"12", "pdf"=>"4", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2014", "month"=>"11"}
• {"unique-ip"=>"16", "full-text"=>"12", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
• {"unique-ip"=>"13", "full-text"=>"11", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
• {"unique-ip"=>"28", "full-text"=>"22", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"11"}
• {"unique-ip"=>"27", "full-text"=>"26", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
• {"unique-ip"=>"17", "full-text"=>"21", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
• {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
• {"unique-ip"=>"23", "full-text"=>"23", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
• {"unique-ip"=>"18", "full-text"=>"20", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
• {"unique-ip"=>"16", "full-text"=>"18", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
• {"unique-ip"=>"17", "full-text"=>"16", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
• {"unique-ip"=>"12", "full-text"=>"11", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
• {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
• {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
• {"unique-ip"=>"19", "full-text"=>"21", "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"=>"26", "full-text"=>"27", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
• {"unique-ip"=>"16", "full-text"=>"11", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
• {"unique-ip"=>"15", "full-text"=>"18", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
• {"unique-ip"=>"22", "full-text"=>"23", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
• {"unique-ip"=>"20", "full-text"=>"22", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
• {"unique-ip"=>"14", "full-text"=>"13", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
• {"unique-ip"=>"19", "full-text"=>"20", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
• {"unique-ip"=>"17", "full-text"=>"18", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
• {"unique-ip"=>"30", "full-text"=>"33", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
• {"unique-ip"=>"32", "full-text"=>"31", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
• {"unique-ip"=>"26", "full-text"=>"26", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
• {"unique-ip"=>"23", "full-text"=>"27", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
• {"unique-ip"=>"22", "full-text"=>"25", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
• {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"2"}
• {"unique-ip"=>"27", "full-text"=>"28", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
• {"unique-ip"=>"25", "full-text"=>"26", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
• {"unique-ip"=>"17", "full-text"=>"20", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
• {"unique-ip"=>"24", "full-text"=>"28", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
• {"unique-ip"=>"29", "full-text"=>"33", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
• {"unique-ip"=>"18", "full-text"=>"18", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
• {"unique-ip"=>"14", "full-text"=>"18", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
• {"unique-ip"=>"17", "full-text"=>"22", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
• {"unique-ip"=>"29", "full-text"=>"40", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
• {"unique-ip"=>"28", "full-text"=>"35", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
• {"unique-ip"=>"21", "full-text"=>"26", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
• {"unique-ip"=>"20", "full-text"=>"27", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
• {"unique-ip"=>"19", "full-text"=>"24", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
• {"unique-ip"=>"34", "full-text"=>"39", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
• {"unique-ip"=>"43", "full-text"=>"56", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
• {"unique-ip"=>"34", "full-text"=>"41", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
• {"unique-ip"=>"35", "full-text"=>"38", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
• {"unique-ip"=>"34", "full-text"=>"40", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}

Relative Metric

{"start_date"=>"2012-01-01T00:00:00Z", "end_date"=>"2012-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[322, 550, 671, 773, 864, 955, 1048, 1135, 1223, 1308, 1387, 1465, 1534, 1602, 1673, 1744, 1813, 1885, 1955, 2026, 2093, 2160, 2228, 2290, 2349]}, {"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[313, 562, 690, 796, 893, 986, 1079, 1173, 1257, 1349, 1429, 1506, 1586, 1661, 1730, 1803, 1876, 1945, 2017, 2091, 2163, 2225, 2294, 2362, 2430]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[312, 547, 668, 769, 861, 953, 1046, 1135, 1224, 1307, 1388, 1464, 1536, 1606, 1676, 1744, 1812, 1882, 1954, 2020, 2089, 2155, 2218, 2282, 2344]}]}

F1000Prime