Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness
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{"title"=>"Lymphangioleiomyomatosis biomarkers linked to lung metastatic potential and cell stemness", "type"=>"journal", "authors"=>[{"first_name"=>"Gorka Ruiz", "last_name"=>"De Garibay", "scopus_author_id"=>"27267507400"}, {"first_name"=>"Carmen", "last_name"=>"Herranz", "scopus_author_id"=>"56814634900"}, {"first_name"=>"Alicia", "last_name"=>"Llorente", "scopus_author_id"=>"56814585400"}, {"first_name"=>"Jacopo", "last_name"=>"Boni", "scopus_author_id"=>"56814554500"}, {"first_name"=>"Jordi", "last_name"=>"Serra-Musach", "scopus_author_id"=>"37051268700"}, {"first_name"=>"Francesca", "last_name"=>"Mateo", "scopus_author_id"=>"15758358700"}, {"first_name"=>"Helena", "last_name"=>"Aguilar", "scopus_author_id"=>"7004357242"}, {"first_name"=>"Laia", "last_name"=>"Gómez-Baldó", "scopus_author_id"=>"24832736100"}, {"first_name"=>"Anna", "last_name"=>"Petit", "scopus_author_id"=>"7101616234"}, {"first_name"=>"August", "last_name"=>"Vidal", "scopus_author_id"=>"35433719800"}, {"first_name"=>"Fina", "last_name"=>"Climent", "scopus_author_id"=>"7003399745"}, {"first_name"=>"Javier", "last_name"=>"Hernández-Losa", "scopus_author_id"=>"23034454900"}, {"first_name"=>"Álex", "last_name"=>"Cordero", "scopus_author_id"=>"56071406500"}, {"first_name"=>"Eva", "last_name"=>"González-Suárez", "scopus_author_id"=>"6507782482"}, {"first_name"=>"José Vicente", "last_name"=>"Sánchez-Mut", "scopus_author_id"=>"15123043200"}, {"first_name"=>"Manel", "last_name"=>"Esteller", "scopus_author_id"=>"14719291800"}, {"first_name"=>"Roger", "last_name"=>"Llatjós", "scopus_author_id"=>"6507147098"}, {"first_name"=>"Mar", "last_name"=>"Varela", "scopus_author_id"=>"56063273200"}, {"first_name"=>"José Ignacio", "last_name"=>"López", "scopus_author_id"=>"7404445435"}, {"first_name"=>"Nadia", "last_name"=>"García", "scopus_author_id"=>"15757511500"}, {"first_name"=>"Ana I.", "last_name"=>"Extremera", "scopus_author_id"=>"56173244200"}, {"first_name"=>"Anna", "last_name"=>"Gumà", "scopus_author_id"=>"36840272200"}, {"first_name"=>"Raúl", "last_name"=>"Ortega", "scopus_author_id"=>"56814349700"}, {"first_name"=>"María Jesús", "last_name"=>"Plà", "scopus_author_id"=>"12783457700"}, {"first_name"=>"Adela", "last_name"=>"Fernández", "scopus_author_id"=>"55605762861"}, {"first_name"=>"Sònia", "last_name"=>"Pernas", "scopus_author_id"=>"11142195700"}, {"first_name"=>"Catalina", "last_name"=>"Falo", "scopus_author_id"=>"56619878400"}, {"first_name"=>"Idoia", "last_name"=>"Morilla", "scopus_author_id"=>"6506127836"}, {"first_name"=>"Miriam", "last_name"=>"Campos", "scopus_author_id"=>"56814284500"}, {"first_name"=>"Miguel", "last_name"=>"Gil", "scopus_author_id"=>"55240048200"}, {"first_name"=>"Antonio", "last_name"=>"Román", "scopus_author_id"=>"7102169163"}, {"first_name"=>"María", "last_name"=>"Molina-Molina", "scopus_author_id"=>"6507158798"}, {"first_name"=>"Piedad", "last_name"=>"Ussetti", "scopus_author_id"=>"6701464905"}, {"first_name"=>"Rosalía", "last_name"=>"Laporta", "scopus_author_id"=>"6602846592"}, {"first_name"=>"Claudia", "last_name"=>"Valenzuela", "scopus_author_id"=>"36843409400"}, {"first_name"=>"Julio", "last_name"=>"Ancochea", "scopus_author_id"=>"56463074900"}, {"first_name"=>"Antoni", "last_name"=>"Xaubet", "scopus_author_id"=>"7005542615"}, {"first_name"=>"Álvaro", "last_name"=>"Casanova", "scopus_author_id"=>"7004144963"}, {"first_name"=>"Miguel Angel", "last_name"=>"Pujana", "scopus_author_id"=>"56618350700"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"26167915", "issn"=>"19326203", "scopus"=>"2-s2.0-84940688735", "pui"=>"605803254", "doi"=>"10.1371/journal.pone.0132546", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"84940688735"}, "id"=>"64466282-86ba-36ac-8a66-e5f7e4d7535d", "abstract"=>"Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ss3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM.", "link"=>"http://www.mendeley.com/research/lymphangioleiomyomatosis-biomarkers-linked-lung-metastatic-potential-cell-stemness", "reader_count"=>20, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Librarian"=>2, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>4, "Student > Master"=>2, "Other"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Librarian"=>2, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. 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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2174121", "https://ndownloader.figshare.com/files/2174122", "https://ndownloader.figshare.com/files/2174123", "https://ndownloader.figshare.com/files/2174124"], "description"=>"<div><p>Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (<i>TSC1</i> or <i>TSC2</i>) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low <i>TSC1/2</i> expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ß3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of <i>Tsc2</i>-deficient cells revealed relative over-expression of FSCN1 and ID1; however, <i>Tsc2</i>-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM.</p></div>", "links"=>[], "tags"=>["aldehyde dehydrogenase 1", "Cell Stemness Lymphangioleiomyomatosis", "luminal progenitor cell biomarkers", "novel LAM biomarkers", "tsc", "ITGB", "23 LAM lesions", "breast cancer", "FSCN", "aldh", "breast cancer datasets", "lung metastasis mediators fascin 1", "sox", "breast cancer metastasis", "id", "immunohistochemical analyses", "DNA binding 1"], "article_id"=>1482002, "categories"=>["Biological Sciences"], "users"=>["Gorka Ruiz de Garibay", "Carmen Herranz", "Alicia Llorente", "Jacopo Boni", "Jordi Serra-Musach", "Francesca Mateo", "Helena Aguilar", "Laia Gómez-Baldó", "Anna Petit", "August Vidal", "Fina Climent", "Javier Hernández-Losa", "Álex Cordero", "Eva González-Suárez", "Jose Vicente Sanchez-Mut", "Manel Esteller", "Roger Llatjós", "Mar Varela", "José Ignacio López", "Nadia García", "Ana I. Extremera", "Anna Gumà", "Raúl Ortega", "María Jesús Plà", "Adela Fernández", "Sònia Pernas", "Catalina Falo", "Idoia Morilla", "Miriam Campos", "Miguel Gil", "Antonio Román", "Maria Molina-Molina", "Piedad Ussetti", "Rosalía Laporta", "Claudia Valenzuela", "Julio Ancochea", "Antoni Xaubet", "Álvaro Casanova", "Miguel Angel Pujana"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0132546.s001", "https://dx.doi.org/10.1371/journal.pone.0132546.s002", "https://dx.doi.org/10.1371/journal.pone.0132546.s003", "https://dx.doi.org/10.1371/journal.pone.0132546.s004"], "stats"=>{"downloads"=>3, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Lymphangioleiomyomatosis_Biomarkers_Linked_to_Lung_Metastatic_Potential_and_Cell_Stemness_/1482002", "title"=>"Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-07-13 03:39:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/2174108"], "description"=>"<p>(A) Representative hematoxylin-eosin and immunohistochemical staining in normal breast tissue. The observed patterns of positivity were those expected with the exception of ALDH1, which could have showed positivity in the basal and luminal cell layers of the acini; nonetheless, this can only be observed at the growing end and branching of the ducts [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132546#pone.0132546.ref048\" target=\"_blank\">48</a>], which may be represented by the image shown in the right panel. Expression of ALDH1, CD61, FSCN1 and SOX9 was also seen in spindle-like cells surrounding the terminal extra-lobular ducts as well as in similar cells of the loose specialized intra-lobular stroma (arrows in insets). The results of CD61 are detailed for the basal cell layer in differentiated acini (a) and for spindle-like intra-lobular cells (b). The arrows mark magnified fields. (B) Representative hematoxylin-eosin and immunohistochemical staining in normal lung tissue. ALDH1 and FSCN1 mark the alveolar endothelium, and ALDH1 also marks the basal and luminal layers of the bronchioles. CD61, ID1 and SOX9 are not expressed in differentiated alveoli, and CD61 and SOX9 show positivity in the luminal and/or basal layers of the bronchioles.</p>", "links"=>[], "tags"=>["aldehyde dehydrogenase 1", "Cell Stemness Lymphangioleiomyomatosis", "luminal progenitor cell biomarkers", "novel LAM biomarkers", "tsc", "ITGB", "23 LAM lesions", "breast cancer", "FSCN", "aldh", "breast cancer datasets", "lung metastasis mediators fascin 1", "sox", "breast cancer metastasis", "id", "immunohistochemical analyses", "DNA binding 1"], "article_id"=>1481989, "categories"=>["Biological Sciences"], "users"=>["Gorka Ruiz de Garibay", "Carmen Herranz", "Alicia Llorente", "Jacopo Boni", "Jordi Serra-Musach", "Francesca Mateo", "Helena Aguilar", "Laia Gómez-Baldó", "Anna Petit", "August Vidal", "Fina Climent", "Javier Hernández-Losa", "Álex Cordero", "Eva González-Suárez", "Jose Vicente Sanchez-Mut", "Manel Esteller", "Roger Llatjós", "Mar Varela", "José Ignacio López", "Nadia García", "Ana I. Extremera", "Anna Gumà", "Raúl Ortega", "María Jesús Plà", "Adela Fernández", "Sònia Pernas", "Catalina Falo", "Idoia Morilla", "Miriam Campos", "Miguel Gil", "Antonio Román", "Maria Molina-Molina", "Piedad Ussetti", "Rosalía Laporta", "Claudia Valenzuela", "Julio Ancochea", "Antoni Xaubet", "Álvaro Casanova", "Miguel Angel Pujana"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132546.g003", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunohistochemical_characterization_of_biomarkers_in_normal_breast_and_lung_tissue_/1481989", "title"=>"Immunohistochemical characterization of biomarkers in normal breast and lung tissue.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-13 03:39:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/2174112"], "description"=>"<p>Representative positive results for ALDH1, CD61 and SOX9 in two LAM cases. Arrows mark magnified fields shown in the insets.</p>", "links"=>[], "tags"=>["aldehyde dehydrogenase 1", "Cell Stemness Lymphangioleiomyomatosis", "luminal progenitor cell biomarkers", "novel LAM biomarkers", "tsc", "ITGB", "23 LAM lesions", "breast cancer", "FSCN", "aldh", "breast cancer datasets", "lung metastasis mediators fascin 1", "sox", "breast cancer metastasis", "id", "immunohistochemical analyses", "DNA binding 1"], "article_id"=>1481993, "categories"=>["Biological Sciences"], "users"=>["Gorka Ruiz de Garibay", "Carmen Herranz", "Alicia Llorente", "Jacopo Boni", "Jordi Serra-Musach", "Francesca Mateo", "Helena Aguilar", "Laia Gómez-Baldó", "Anna Petit", "August Vidal", "Fina Climent", "Javier Hernández-Losa", "Álex Cordero", "Eva González-Suárez", "Jose Vicente Sanchez-Mut", "Manel Esteller", "Roger Llatjós", "Mar Varela", "José Ignacio López", "Nadia García", "Ana I. Extremera", "Anna Gumà", "Raúl Ortega", "María Jesús Plà", "Adela Fernández", "Sònia Pernas", "Catalina Falo", "Idoia Morilla", "Miriam Campos", "Miguel Gil", "Antonio Román", "Maria Molina-Molina", "Piedad Ussetti", "Rosalía Laporta", "Claudia Valenzuela", "Julio Ancochea", "Antoni Xaubet", "Álvaro Casanova", "Miguel Angel Pujana"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132546.g004", "stats"=>{"downloads"=>2, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Positivity_for_breast_cancer_stemness_biomarkers_in_LAM_tissue_/1481993", "title"=>"Positivity for breast cancer stemness biomarkers in LAM tissue.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-13 03:39:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/2174097"], "description"=>"<p>(A) Kaplan-Meier lung metastasis-free survival (LMFS) and bone metastasis-free survival (BMFS) curves based on categorization of <i>TSC2</i> expression. The <i>P</i> values of the Cox proportional-hazards regression analysis are shown. (B) Tumor sample and gene expression clustering, and correlations of <i>TSC1/2</i> and genes from the lung metastasis signature, in the seminal breast cancer dataset [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132546#pone.0132546.ref027\" target=\"_blank\">27</a>]. (C) GSEA results for Cox regression values of the mTOR pathway gene set and LMFS or BMFS. (D) GSEA results for Cox regression values of metabolic pathway gene sets and LMFS or BMFS. (E) Tumor sample and gene expression clustering, and correlations between <i>TSC1/2</i> and genes from lung metastasis signature, in the TCGA dataset [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132546#pone.0132546.ref070\" target=\"_blank\">70</a>]. (F) GSEA results for the expression difference of the lung metastasis signature between MCF7 cells transduced with control or <i>TSC2</i>-target shRNAs. The left top panel shows the results for absolute expression differences, and the middle and bottom panels show the results for real differences of the up-regulated and down-regulated subsets of the signature, respectively. The right panels show the Western blot results for tuberin, pS6 and control loading, TUBA.</p>", "links"=>[], "tags"=>["aldehyde dehydrogenase 1", "Cell Stemness Lymphangioleiomyomatosis", "luminal progenitor cell biomarkers", "novel LAM biomarkers", "tsc", "ITGB", "23 LAM lesions", "breast cancer", "FSCN", "aldh", "breast cancer datasets", "lung metastasis mediators fascin 1", "sox", "breast cancer metastasis", "id", "immunohistochemical analyses", "DNA binding 1"], "article_id"=>1481978, "categories"=>["Biological Sciences"], "users"=>["Gorka Ruiz de Garibay", "Carmen Herranz", "Alicia Llorente", "Jacopo Boni", "Jordi Serra-Musach", "Francesca Mateo", "Helena Aguilar", "Laia Gómez-Baldó", "Anna Petit", "August Vidal", "Fina Climent", "Javier Hernández-Losa", "Álex Cordero", "Eva González-Suárez", "Jose Vicente Sanchez-Mut", "Manel Esteller", "Roger Llatjós", "Mar Varela", "José Ignacio López", "Nadia García", "Ana I. Extremera", "Anna Gumà", "Raúl Ortega", "María Jesús Plà", "Adela Fernández", "Sònia Pernas", "Catalina Falo", "Idoia Morilla", "Miriam Campos", "Miguel Gil", "Antonio Román", "Maria Molina-Molina", "Piedad Ussetti", "Rosalía Laporta", "Claudia Valenzuela", "Julio Ancochea", "Antoni Xaubet", "Álvaro Casanova", "Miguel Angel Pujana"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132546.g001", "stats"=>{"downloads"=>2, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_mTOR_pathway_components_and_breast_cancer_metastasis_to_lung_/1481978", "title"=>"Expression of mTOR pathway components and breast cancer metastasis to lung.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-13 03:39:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/2174102"], "description"=>"<p>(A) Representative results for FSCN1 and ID1 in two LAM cases. Arrows mark magnified fields shown in the insets. (B) Representative immunohistochemistry results for CD34 and FSCN1 in LAM tissue. Positivity for FSCN1 is greater and not limited to endothelial cells.</p>", "links"=>[], "tags"=>["aldehyde dehydrogenase 1", "Cell Stemness Lymphangioleiomyomatosis", "luminal progenitor cell biomarkers", "novel LAM biomarkers", "tsc", "ITGB", "23 LAM lesions", "breast cancer", "FSCN", "aldh", "breast cancer datasets", "lung metastasis mediators fascin 1", "sox", "breast cancer metastasis", "id", "immunohistochemical analyses", "DNA binding 1"], "article_id"=>1481983, "categories"=>["Biological Sciences"], "users"=>["Gorka Ruiz de Garibay", "Carmen Herranz", "Alicia Llorente", "Jacopo Boni", "Jordi Serra-Musach", "Francesca Mateo", "Helena Aguilar", "Laia Gómez-Baldó", "Anna Petit", "August Vidal", "Fina Climent", "Javier Hernández-Losa", "Álex Cordero", "Eva González-Suárez", "Jose Vicente Sanchez-Mut", "Manel Esteller", "Roger Llatjós", "Mar Varela", "José Ignacio López", "Nadia García", "Ana I. Extremera", "Anna Gumà", "Raúl Ortega", "María Jesús Plà", "Adela Fernández", "Sònia Pernas", "Catalina Falo", "Idoia Morilla", "Miriam Campos", "Miguel Gil", "Antonio Román", "Maria Molina-Molina", "Piedad Ussetti", "Rosalía Laporta", "Claudia Valenzuela", "Julio Ancochea", "Antoni Xaubet", "Álvaro Casanova", "Miguel Angel Pujana"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132546.g002", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Positivity_for_breast_cancer_lung_metastasis_mediators_in_LAM_tissue_/1481983", "title"=>"Positivity for breast cancer lung metastasis mediators in LAM tissue.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-13 03:39:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/2174117"], "description"=>"<p>(A) Left panels, details of immunohistochemical results for canonical and novel biomarkers (FSNC1 and ID1) in a given LAM lesion, revealing expression heterogeneity. Right panels, evidence of heterogeneity based on the staining of SMA and FSCN1, SMA and ID1, and SMA and HMB-45 in three independent lesions/cases. (B) Top panel, heterogeneity for pS6 staining in a characteristic LAM cystic structure. The arrows mark two different tissue regions (a, b) that are magnified (bottom panels) for the immunohistochemical results of pS6 and the novel biomarkers. (C) Double immunofluorescence staining results also show intra-tissue heterogeneity for the novel biomarkers. (D) In large LAM lesions, pS6 is mostly apparent at the front.</p>", "links"=>[], "tags"=>["aldehyde dehydrogenase 1", "Cell Stemness Lymphangioleiomyomatosis", "luminal progenitor cell biomarkers", "novel LAM biomarkers", "tsc", "ITGB", "23 LAM lesions", "breast cancer", "FSCN", "aldh", "breast cancer datasets", "lung metastasis mediators fascin 1", "sox", "breast cancer metastasis", "id", "immunohistochemical analyses", "DNA binding 1"], "article_id"=>1481998, "categories"=>["Biological Sciences"], "users"=>["Gorka Ruiz de Garibay", "Carmen Herranz", "Alicia Llorente", "Jacopo Boni", "Jordi Serra-Musach", "Francesca Mateo", "Helena Aguilar", "Laia Gómez-Baldó", "Anna Petit", "August Vidal", "Fina Climent", "Javier Hernández-Losa", "Álex Cordero", "Eva González-Suárez", "Jose Vicente Sanchez-Mut", "Manel Esteller", "Roger Llatjós", "Mar Varela", "José Ignacio López", "Nadia García", "Ana I. Extremera", "Anna Gumà", "Raúl Ortega", "María Jesús Plà", "Adela Fernández", "Sònia Pernas", "Catalina Falo", "Idoia Morilla", "Miriam Campos", "Miguel Gil", "Antonio Román", "Maria Molina-Molina", "Piedad Ussetti", "Rosalía Laporta", "Claudia Valenzuela", "Julio Ancochea", "Antoni Xaubet", "Álvaro Casanova", "Miguel Angel Pujana"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132546.g005", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Intra_tissue_and_inter_case_heterogeneity_in_the_staining_of_canonical_and_novel_LAM_biomarkers_/1481998", "title"=>"Intra-tissue and inter-case heterogeneity in the staining of canonical and novel LAM biomarkers.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-13 03:39:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/2174118"], "description"=>"<p>(A) Western blot results for FSCN1 and ID1, and controls tuberin, pS6 and TUBA in two <i>Tsc2</i>-deficient cell models and their control counterparts. (B) Western blot results for the same biomarkers in cells exposed to everolimus or control solution. (C) Graphs showing the dose-response curves of MEF and ELT3 cell lines exposed to everolimus. (D) Graphs showing the dose-response curves of MEF cell lines exposed to each one of the ID1-expression inhibitors. (E) Western blot results for ID1 and control TUBA in MEF cell lines exposed to the corresponding inhibitors or control solutions.</p>", "links"=>[], "tags"=>["aldehyde dehydrogenase 1", "Cell Stemness Lymphangioleiomyomatosis", "luminal progenitor cell biomarkers", "novel LAM biomarkers", "tsc", "ITGB", "23 LAM lesions", "breast cancer", "FSCN", "aldh", "breast cancer datasets", "lung metastasis mediators fascin 1", "sox", "breast cancer metastasis", "id", "immunohistochemical analyses", "DNA binding 1"], "article_id"=>1481999, "categories"=>["Biological Sciences"], "users"=>["Gorka Ruiz de Garibay", "Carmen Herranz", "Alicia Llorente", "Jacopo Boni", "Jordi Serra-Musach", "Francesca Mateo", "Helena Aguilar", "Laia Gómez-Baldó", "Anna Petit", "August Vidal", "Fina Climent", "Javier Hernández-Losa", "Álex Cordero", "Eva González-Suárez", "Jose Vicente Sanchez-Mut", "Manel Esteller", "Roger Llatjós", "Mar Varela", "José Ignacio López", "Nadia García", "Ana I. Extremera", "Anna Gumà", "Raúl Ortega", "María Jesús Plà", "Adela Fernández", "Sònia Pernas", "Catalina Falo", "Idoia Morilla", "Miriam Campos", "Miguel Gil", "Antonio Román", "Maria Molina-Molina", "Piedad Ussetti", "Rosalía Laporta", "Claudia Valenzuela", "Julio Ancochea", "Antoni Xaubet", "Álvaro Casanova", "Miguel Angel Pujana"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0132546.g006", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_biomarkers_and_ID1_based_therapeutic_evaluation_in_Tsc2_defient_cells_/1481999", "title"=>"Expression of biomarkers and ID1-based therapeutic evaluation in <i>Tsc2</i>-defient cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-13 03:39:45"}

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  • {"unique-ip"=>"6", "full-text"=>"4", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"22", "full-text"=>"19", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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