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{"title"=>"Aberrant promoter methylation of Caveolin-1 is associated with favorable response to taxane-platinum combination chemotherapy in advanced NSCLC", "type"=>"journal", "authors"=>[{"first_name"=>"Seth A.", "last_name"=>"Brodie", "scopus_author_id"=>"54954086300"}, {"first_name"=>"Courtney", "last_name"=>"Lombardo", "scopus_author_id"=>"56362470000"}, {"first_name"=>"Ge", "last_name"=>"Li", "scopus_author_id"=>"55627804100"}, {"first_name"=>"Jeanne", "last_name"=>"Kowalski", "scopus_author_id"=>"7201647693"}, {"first_name"=>"Khanjan", "last_name"=>"Gandhi", "scopus_author_id"=>"41861553300"}, {"first_name"=>"Shaojin", "last_name"=>"You", "scopus_author_id"=>"8705189100"}, {"first_name"=>"Fadlo R.", "last_name"=>"Khuri", "scopus_author_id"=>"7007043446"}, {"first_name"=>"Adam", "last_name"=>"Marcus", "scopus_author_id"=>"36070611500"}, {"first_name"=>"Paula M.", "last_name"=>"Vertino", "scopus_author_id"=>"6701689709"}, {"first_name"=>"Johann C.", "last_name"=>"Brandes", "scopus_author_id"=>"9732982500"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"25222296", "sgr"=>"84907149050", "doi"=>"10.1371/journal.pone.0107124", "scopus"=>"2-s2.0-84907149050", "pui"=>"600033376", "isbn"=>"1932-6203", "issn"=>"19326203"}, "id"=>"db8350d8-0780-326b-85d3-cef6c5675e11", "abstract"=>"PURPOSE: Aberrant promoter DNA methylation can serve as a predictive biomarker for improved clinical responses to certain chemotherapeutics. One of the major advantages of methylation biomarkers is the ease of detection and clinical application. In order to identify methylation biomarkers predictive of a response to a taxane-platinum based chemotherapy regimen in advanced NSCLC we performed an unbiased methylation analysis of 1,536 CpG dinucleotides in cancer-associated gene loci and correlated results with clinical outcomes.\\n\\nMETHODS: We studied a cohort of 49 patients (median age 62 years) with advanced NSCLC treated at the Atlanta VAMC between 1999 and 2010. Methylation analysis was done on the Illumina GoldenGate Cancer panel 1 methylation microarray platform. Methylation data were correlated with clinical response and adjusted for false discovery rates.\\n\\nRESULTS: Cav1 methylation emerged as a powerful predictor for achieving disease stabilization following platinum taxane based chemotherapy (p = 1.21E-05, FDR significance  = 0.018176). In Cox regression analysis after multivariate adjustment for age, performance status, gender, histology and the use of bevacizumab, CAV1 methylation was significantly associated with improved overall survival (HR 0.18 (95%CI: 0.03-0.94)). Silencing of CAV1 expression in lung cancer cell lines(A549, EKVX)by shRNA led to alterations in taxane retention.\\n\\nCONCLUSIONS: CAV1 methylation is a predictor of disease stabilization and improved overall survival following chemotherapy with a taxane-platinum combination regimen in advanced NSCLC. CAV1 methylation may predict improved outcomes for other chemotherapeutic agents which are subject to cellular clearance mediated by caveolae.", "link"=>"http://www.mendeley.com/research/aberrant-promoter-methylation-caveolin1-associated-favorable-response-taxaneplatinum-combination-che", "reader_count"=>10, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>1, "Student > Ph. D. Student"=>4, "Professor"=>1, "Other"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>1, "Student > Ph. D. Student"=>4, "Professor"=>1, "Other"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Mathematics"=>1, "Medicine and Dentistry"=>4, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Germany"=>1}, "group_count"=>0}

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• http://doi.org/10.18632/oncotarget.5789
• http://doi.org/10.1002/ijc.31369
• http://doi.org/10.3389/fphar.2018.01106
• http://doi.org/10.18632/oncotarget.4988
• http://doi.org/10.1002/jcp.27196
• http://doi.org/10.1002/ctm2.2
• http://doi.org/10.1186/s12935-019-0892-0
• http://doi.org/10.1007/s13277-015-4012-z
• http://doi.org/10.1038/s41397-018-0029-1

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/1676863"], "description"=>"<p>Clinical characteristics.</p>", "links"=>[], "tags"=>["Aberrant Promoter Methylation", "CAV 1 expression", "hr", "fdr", "discovery rates.ResultsCav 1 methylation", "methylation biomarkers", "taxane retention.ConclusionsCAV 1 methylation", "age 62 years", "disease stabilization", "ci", "VAMC", "Advanced NSCLC PurposeAberrant promoter DNA methylation", "CAV 1 methylation", "ekvx", "2010. Methylation analysis", "Cox regression analysis", "Illumina GoldenGate Cancer panel 1 methylation microarray platform"], "article_id"=>1170720, "categories"=>["Biological Sciences"], "users"=>["Seth A. Brodie", "Courtney Lombardo", "Ge Li", "Jeanne Kowalski", "Khanjan Gandhi", "Shaojin You", "Fadlo R. Khuri", "Adam Marcus", "Paula M. Vertino", "Johann C. Brandes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107124.t001", "stats"=>{"downloads"=>4, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_characteristics_/1170720", "title"=>"Clinical characteristics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-09-15 03:11:58"}
• {"files"=>["https://ndownloader.figshare.com/files/1676865"], "description"=>"<p>Multivariate analysis.</p>", "links"=>[], "tags"=>["Aberrant Promoter Methylation", "CAV 1 expression", "hr", "fdr", "discovery rates.ResultsCav 1 methylation", "methylation biomarkers", "taxane retention.ConclusionsCAV 1 methylation", "age 62 years", "disease stabilization", "ci", "VAMC", "Advanced NSCLC PurposeAberrant promoter DNA methylation", "CAV 1 methylation", "ekvx", "2010. Methylation analysis", "Cox regression analysis", "Illumina GoldenGate Cancer panel 1 methylation microarray platform"], "article_id"=>1170722, "categories"=>["Biological Sciences"], "users"=>["Seth A. Brodie", "Courtney Lombardo", "Ge Li", "Jeanne Kowalski", "Khanjan Gandhi", "Shaojin You", "Fadlo R. Khuri", "Adam Marcus", "Paula M. Vertino", "Johann C. Brandes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107124.t002", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Multivariate_analysis_/1170722", "title"=>"Multivariate analysis.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-09-15 03:11:58"}
• {"files"=>["https://ndownloader.figshare.com/files/1676836"], "description"=>"<p>A) morphologic changes toward spindle shaped cells after CAV1 shRNA knockdown are observed in A549 cells compared to scrambled shRNA. No such changes are observed in HOP-62 cells which have undergone EMT already. B) CAV1 silencing is associated with reduced expression of E-cadherin and an increase in SLUG expression, both consistent with EMT. Increased FAK-phosphorylation (Y397) signaling serves as a marker for a pro-migratory phenotype C) CAV1 silencing increases cell migration in a wound healing assay D) Quantification of wound healing assays p values (two tailed Student's t) 8 hr p = 0.036, 24 hr p = 0.023, 32 hr p = 0.015, 48 hr p = 0.045.</p>", "links"=>[], "tags"=>["Aberrant Promoter Methylation", "CAV 1 expression", "hr", "fdr", "discovery rates.ResultsCav 1 methylation", "methylation biomarkers", "taxane retention.ConclusionsCAV 1 methylation", "age 62 years", "disease stabilization", "ci", "VAMC", "Advanced NSCLC PurposeAberrant promoter DNA methylation", "CAV 1 methylation", "ekvx", "2010. Methylation analysis", "Cox regression analysis", "Illumina GoldenGate Cancer panel 1 methylation microarray platform"], "article_id"=>1170707, "categories"=>["Biological Sciences"], "users"=>["Seth A. Brodie", "Courtney Lombardo", "Ge Li", "Jeanne Kowalski", "Khanjan Gandhi", "Shaojin You", "Fadlo R. Khuri", "Adam Marcus", "Paula M. Vertino", "Johann C. Brandes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107124.g002", "stats"=>{"downloads"=>2, "page_views"=>106, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stable_shRNA_knockdown_induced_an_epithelial_mesenchymal_transformation_phenotype_in_A549_cells_/1170707", "title"=>"Stable shRNA knockdown induced an epithelial mesenchymal transformation phenotype in A549 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-15 03:11:58"}
• {"files"=>["https://ndownloader.figshare.com/files/1676840"], "description"=>"<p>A: CAV1 silencing increases taxane sensitivity in colony formation assays in a549 and HOP62 NSCLC cell lines. Error bars represent standard deviations, p-value <0.05. B: No impact of CAV1 silencing is observed in relationship to cisplatin sensitivity. C: CAV1 silencing leads to increased intracellular taxol concentrations. Live cell microscopy assays were performed in the presence of fluorescently labeled taxol (Flutax). Red- and green fluorescent images were obtained at a frequency of 1.2 images/min. Green fluorescence was analyzed in red-fluorescent cells and plotted over 50 cycles. Statistical analysis was by trapezoid rule (p-value p = 6.66×10⁻⁹). D: CAV1 silencing is associated with reduced protein expression of MDR-1 in Hop-62 cells but not in A549 cells.</p>", "links"=>[], "tags"=>["Aberrant Promoter Methylation", "CAV 1 expression", "hr", "fdr", "discovery rates.ResultsCav 1 methylation", "methylation biomarkers", "taxane retention.ConclusionsCAV 1 methylation", "age 62 years", "disease stabilization", "ci", "VAMC", "Advanced NSCLC PurposeAberrant promoter DNA methylation", "CAV 1 methylation", "ekvx", "2010. Methylation analysis", "Cox regression analysis", "Illumina GoldenGate Cancer panel 1 methylation microarray platform"], "article_id"=>1170711, "categories"=>["Biological Sciences"], "users"=>["Seth A. Brodie", "Courtney Lombardo", "Ge Li", "Jeanne Kowalski", "Khanjan Gandhi", "Shaojin You", "Fadlo R. Khuri", "Adam Marcus", "Paula M. Vertino", "Johann C. Brandes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107124.g003", "stats"=>{"downloads"=>0, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Loss_of_CAV1_increases_taxane_sensitivity_by_decreasing_taxane_turnover_independent_of_loss_of_MDR1_/1170711", "title"=>"Loss of CAV1 increases taxane sensitivity, by decreasing taxane turnover independent of loss of MDR1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-15 03:11:58"}
• {"files"=>["https://ndownloader.figshare.com/files/1676822"], "description"=>"<p>A) Hierarchical clustering of the most prominent changes in relationship at clinical response. B) CAV1 methylation is (by methylation beta-value) is statistically significantly associated with stable disease. C) differences in CAV1 m-RNA expression by qRT-PCR between the three groups of clinical outcomes show a statistically non-significant trend towards decreased expression in patients with SD.</p>", "links"=>[], "tags"=>["Aberrant Promoter Methylation", "CAV 1 expression", "hr", "fdr", "discovery rates.ResultsCav 1 methylation", "methylation biomarkers", "taxane retention.ConclusionsCAV 1 methylation", "age 62 years", "disease stabilization", "ci", "VAMC", "Advanced NSCLC PurposeAberrant promoter DNA methylation", "CAV 1 methylation", "ekvx", "2010. Methylation analysis", "Cox regression analysis", "Illumina GoldenGate Cancer panel 1 methylation microarray platform"], "article_id"=>1170697, "categories"=>["Biological Sciences"], "users"=>["Seth A. Brodie", "Courtney Lombardo", "Ge Li", "Jeanne Kowalski", "Khanjan Gandhi", "Shaojin You", "Fadlo R. Khuri", "Adam Marcus", "Paula M. Vertino", "Johann C. Brandes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107124.g001", "stats"=>{"downloads"=>3, "page_views"=>87, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_three_way_analysis_between_Progressive_Disease_PD_stable_disease_SD_and_Partial_Response_PR_was_performed_based_on_an_F_statistic_based_ANOVA_with_a_FDR_corrected_p_value_lt_0_05_/1170697", "title"=>"A three way analysis between Progressive Disease (PD), stable disease (SD) and Partial Response (PR) was performed based on an F-statistic based ANOVA with a FDR corrected p-value <0.05.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-15 03:11:58"}
• {"files"=>["https://ndownloader.figshare.com/files/1676860"], "description"=>"<p>Out of 1,715 datasets, 144 had clinical information on both stage and overall survival. After adjusting for stage in a multivariate analysis reduced CAV1 expression was associated with improved survival only in patients who received chemotherapy (A) but not in patient who did not (B).</p>", "links"=>[], "tags"=>["Aberrant Promoter Methylation", "CAV 1 expression", "hr", "fdr", "discovery rates.ResultsCav 1 methylation", "methylation biomarkers", "taxane retention.ConclusionsCAV 1 methylation", "age 62 years", "disease stabilization", "ci", "VAMC", "Advanced NSCLC PurposeAberrant promoter DNA methylation", "CAV 1 methylation", "ekvx", "2010. Methylation analysis", "Cox regression analysis", "Illumina GoldenGate Cancer panel 1 methylation microarray platform"], "article_id"=>1170717, "categories"=>["Biological Sciences"], "users"=>["Seth A. Brodie", "Courtney Lombardo", "Ge Li", "Jeanne Kowalski", "Khanjan Gandhi", "Shaojin You", "Fadlo R. Khuri", "Adam Marcus", "Paula M. Vertino", "Johann C. Brandes"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107124.g004", "stats"=>{"downloads"=>0, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overall_survival_was_analyzed_by_CAV1_expression_status_as_determined_by_Affymetrix_gene_expression_array_in_patients_who_received_chemotherapy_and_those_who_did_not_/1170717", "title"=>"Overall survival was analyzed by CAV1 expression status as determined by Affymetrix gene-expression array in patients who received chemotherapy and those who did not.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-15 03:11:58"}

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Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Medicine and health sciences", "average_usage"=>[285]}, {"subject_area"=>"/Medicine and health sciences/Pharmaceutics", "average_usage"=>[299, 467]}, {"subject_area"=>"/Physical sciences", "average_usage"=>[271]}, {"subject_area"=>"/Physical sciences/Chemistry", "average_usage"=>[262]}]}

F1000Prime