High Expression Levels of Total IGF-1R and Sensitivity of NSCLC Cells In Vitro to an Anti-IGF-1R Antibody (R1507)
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{"title"=>"High expression levels of total IGF-1R and sensitivity of NSCLC cells in vitro to an anti-lGF-1R antibody (R1507)", "type"=>"journal", "authors"=>[{"first_name"=>"Yixuan", "last_name"=>"Gong", "scopus_author_id"=>"15071572700"}, {"first_name"=>"Evelyn", "last_name"=>"Yao", "scopus_author_id"=>"35214162500"}, {"first_name"=>"Ronglai", "last_name"=>"Shen", "scopus_author_id"=>"8636749400"}, {"first_name"=>"Aviva", "last_name"=>"Goel", "scopus_author_id"=>"35078531900"}, {"first_name"=>"Maria", "last_name"=>"Arcila", "scopus_author_id"=>"6603171437"}, {"first_name"=>"Julie", "last_name"=>"Teruya-Feldstein", "scopus_author_id"=>"7004187581"}, {"first_name"=>"Maureen F.", "last_name"=>"Zakowski", "scopus_author_id"=>"7005637900"}, {"first_name"=>"Stanley", "last_name"=>"Frankel", "scopus_author_id"=>"57198221365"}, {"first_name"=>"Martin", "last_name"=>"Peifer", "scopus_author_id"=>"12766980700"}, {"first_name"=>"Roman K.", "last_name"=>"Thomas", "scopus_author_id"=>"9535342500"}, {"first_name"=>"Marc", "last_name"=>"Ladanyi", "scopus_author_id"=>"7006141808"}, {"first_name"=>"William", "last_name"=>"Pao", "scopus_author_id"=>"7003342279"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-70350218696", "pui"=>"355461861", "doi"=>"10.1371/journal.pone.0007273", "sgr"=>"70350218696"}, "id"=>"32c11116-4730-3ba1-88a4-19bd0168452c", "abstract"=>"Background: The IGF-1R (IGF receptor type 1) pathway is frequently deregulated in human tumors and has become a target of interest for anti-cancer therapy. We investigated predictive biomarkers of response to an anti-IGF-1R antibody (Ab) in vitro in NSCLC. Methods: We examined the growth inhibitory effects of R1507, a fully-humanized IgG1 anti-IGF-1R monoclonal Ab (Roche), against a panel of 22 NSCLC cell lines using CellTiter Blue assays. Phospho-receptor tyrosine kinase (pRTK) arrays and ELISAs were used to determine the status of IGF-1R and other RTKs. SNP arrays were used to determine IGF-1R copy number. Immunohistochemical (IHC) staining of total IGF-1R was performed with G11 (an anti-total IGF-1R Ab; Ventana) on a tissue microarray (TMA) containing 77 independent NSCLC tumor samples. Staining intensity was scored on a scale of 0 to 3+ by a pathologist (JF). Results: 5 of 22 NSCLC cell lines were moderately sensitive (25-50% growth inhibition) to R1507 alone. ELISA and pRTK array analysis demonstrated that pIGF-1R levels in the presence or absence of serum did not correlate with drug sensitivity. However, 4 of 5 sensitive lines displayed high levels of total IGF-1R vs 1/17 resistant lines (p=0.003 Fisher's Exact). SNP array analysis showed that sensitive lines also harbor relatively higher copy numbers of IGF-1R. There was no correlation with EGFR/KRAS mutational status. 48% of TMA NSCLC tumors had scores of 2+ or greater, while 5% were scored as 3+. Addition of erlotinib or paclitaxel to R1507 led to further growth inhibition in sensitive but not resistant lines. In one EGFR mutant lung adenocarcinoma cell line, R1507 and erlotinib co-treatment induced apoptosis, whereas treatment with either drug alone induced only cell cycle arrest. Apoptosis was mediated, in part, by the survival-related AKT pathway, as pAKT was significantly downregulated by R1507 but not erlotinib. Conclusions: In NSCLC cell lines, high levels of total IGF-1R are associated with moderate sensitivity to R1507. These results suggest a possible enrichment strategy for clinical trials with anti-IGF-1R therapy.", "link"=>"http://www.mendeley.com/research/high-expression-levels-total-igf1r-sensitivity-nsclc-cells-vitro-antilgf1r-antibody-r1507", "reader_count"=>5, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Student > Ph. D. Student"=>2, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Student > Ph. D. Student"=>2, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Medicine and Dentistry"=>1, "Agricultural and Biological Sciences"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Belgium"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/881769"], "description"=>"<p>Adeno – adenocarcinoma. SCC – squamous cell carcinoma. F – female. M – male. Never smoker – smoked less than 100 cigarettes in a lifetime. Age is shown ± standard deviation. Tumors with 2+ to 3+ staining levels were considered IGF-1R(+), while tumors with 0 to 1+ levels were considered IGF-1R(-). Fisher’s exact test was performed to analyze the association of IGF-1R with histology, sex, and smoking history. Two-sample t-test was performed to evaluate IGF-1R association with age. </p><p>Note: the numbers do not add up to 270 because not all clinical variables were available for all samples examined.</p>", "links"=>[], "tags"=>["igf-1r"], "article_id"=>552219, "categories"=>["Cancer", "Cell Biology"], "users"=>["Yixuan Gong", "Evelyn Yao", "Ronglai Shen", "Aviva Goel", "Maria Arcila", "Julie Teruya-Feldstein", "Maureen F. Zakowski", "Stanley Frankel", "Martin Peifer", "Roman K. Thomas", "Marc Ladanyi", "William Pao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007273.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_of_IGF_1R_status_with_clinical_variables_/552219", "title"=>"Association of IGF-1R status with clinical variables.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-10-06 00:36:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/881654"], "description"=>"<p>A. IGF-1R expression in NSCLC cells lines assessed by IHC analysis. IHC was performed on paraffin-embedded NSCLC cell lines using the total IGF-1R antibody, G11 (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007273#s2\" target=\"_blank\">methods</a>). <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007273#s3\" target=\"_blank\">Results</a> were consistent with data obtained from total IGF-1R ELISAs. B. IGF-1R expression in primary NSCLC tumors. IHC staining with G11 was performed on NSCLC tissue microarrays and scored as follows: 0, no staining; 1, weak focal staining; 2, moderate staining; 3, strong staining with at least 10% of the core showing complete membranous staining. Representative images are shown. C. Distribution of scores for total IGF-1R staining in primary NSCLCs. D. Kaplan-Meier curves for overall survival in patients whose tumors scored 0 and 1+ versus 2+ to 3+.</p>", "links"=>[], "tags"=>["nsclc"], "article_id"=>552102, "categories"=>["Cancer", "Cell Biology"], "users"=>["Yixuan Gong", "Evelyn Yao", "Ronglai Shen", "Aviva Goel", "Maria Arcila", "Julie Teruya-Feldstein", "Maureen F. Zakowski", "Stanley Frankel", "Martin Peifer", "Roman K. Thomas", "Marc Ladanyi", "William Pao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007273.g006", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IGF_1R_expression_in_primary_NSCLC_tissues_/552102", "title"=>"IGF-1R expression in primary NSCLC tissues.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-06 00:35:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/881238"], "description"=>"<p>Cell lines are listed from left to right according to <i>IGF-1R</i> gene copy number, highest (red) to lowest (blue). See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007273#s2\" target=\"_blank\">methods</a> for details.</p>", "links"=>[], "tags"=>["nsclc"], "article_id"=>551683, "categories"=>["Cancer", "Cell Biology"], "users"=>["Yixuan Gong", "Evelyn Yao", "Ronglai Shen", "Aviva Goel", "Maria Arcila", "Julie Teruya-Feldstein", "Maureen F. Zakowski", "Stanley Frankel", "Martin Peifer", "Roman K. Thomas", "Marc Ladanyi", "William Pao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007273.g003", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SNP_array_analysis_of_IGF_1R_gene_copy_number_status_in_a_panel_of_NSCLC_cell_lines_/551683", "title"=>"SNP array analysis of <i>IGF-1R</i> gene copy number status in a panel of NSCLC cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-06 00:28:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/880977"], "description"=>"<p>Various cell lines were treated with R1507 for 72 hours, and cell growth inhibition was measured using CellTiter Blue reagents. The maximum growth inhibition obtained at an R1507 concentration of 25 µg/ml was plotted for each cell line. Data represent the mean ± standard deviation of triplicates.</p>", "links"=>[], "tags"=>["lines", "differential"], "article_id"=>551425, "categories"=>["Cancer", "Cell Biology"], "users"=>["Yixuan Gong", "Evelyn Yao", "Ronglai Shen", "Aviva Goel", "Maria Arcila", "Julie Teruya-Feldstein", "Maureen F. Zakowski", "Stanley Frankel", "Martin Peifer", "Roman K. Thomas", "Marc Ladanyi", "William Pao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007273.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_NSCLC_cell_lines_display_differential_sensitivity_to_single_agent_R1507_/551425", "title"=>"NSCLC cell lines display differential sensitivity to single agent R1507.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-06 00:23:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/881392"], "description"=>"<p>A–D. Cells were serum-starved overnight and then stimulated with the indicated concentrations of EGF, IGF-1, or both for 15 minutes. Additional cells were pre-treated with the indicated concentrations of erlotinib, R1507, or both for 3 hours. Cell lysates were analyzed by immunoblotting, using the indicated antibodies. t: total protein; p: phospho-protein. E. 11–18 cells were transfected with siRNAs against the various indicated targets. 48 hours later, cells were harvested, and lysates were analyzed by immunoblotting, using the indicated antibodies.</p>", "links"=>[], "tags"=>["signaling", "akt", "activation"], "article_id"=>551833, "categories"=>["Cancer", "Cell Biology"], "users"=>["Yixuan Gong", "Evelyn Yao", "Ronglai Shen", "Aviva Goel", "Maria Arcila", "Julie Teruya-Feldstein", "Maureen F. Zakowski", "Stanley Frankel", "Martin Peifer", "Roman K. Thomas", "Marc Ladanyi", "William Pao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007273.g004", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IGF_1R_signaling_is_necessary_and_sufficient_for_the_maintenance_of_AKT_activation_in_sensitive_cells_/551833", "title"=>"IGF-1R signaling is necessary and sufficient for the maintenance of AKT activation in sensitive cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-06 00:30:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/881525"], "description"=>"<p>A. R1507 enhances erlotinib-induced growth inhibition in R1507 sensitive cell lines. Various cell lines were treated with increasing concentrations of erlotinib in the absence or presence of 25 µg/ml R1507 for 72 hours and cell growth inhibition was measured by CellTiter Blue reagents. Data represent the mean ± standard deviation of triplicates. B. The combination of R1507 and erlotinib induced apoptosis in 11–18 cells. 11–18 cells were co-treated with 100 or 500 nM erlotinib in the absence or presence of 25 µg/ml R1507 for 24 hours. The percentage of apoptotic cells (annexin V positive cells) was determined by annexin V/PI apoptosis assays.</p>", "links"=>[], "tags"=>["combinatorial", "r1507", "erlotinib", "nsclc"], "article_id"=>551973, "categories"=>["Cancer", "Cell Biology"], "users"=>["Yixuan Gong", "Evelyn Yao", "Ronglai Shen", "Aviva Goel", "Maria Arcila", "Julie Teruya-Feldstein", "Maureen F. Zakowski", "Stanley Frankel", "Martin Peifer", "Roman K. Thomas", "Marc Ladanyi", "William Pao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007273.g005", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_combinatorial_effect_of_R1507_and_erlotinib_in_NSCLC_cell_lines_/551973", "title"=>"The combinatorial effect of R1507 and erlotinib in NSCLC cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-06 00:32:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/881106"], "description"=>"<p>A. Cell lines were serum starved overnight, then stimulated with either 10% FBS, or 10% FBS plus 50 ng/ml IGF-1 for 15 minutes. Cell lysates were obtained for phospho IGF-1R ELISA analysis. Y axis is expressed as absorbance at 450 nm, as no standard curve was available to calculate absolute amount. B. Cell lines were serum starved overnight and lysates were obtained for total IGF-1R ELISA analysis. Cell lines are listed according to their relative sensitivity to R1507.</p>", "links"=>[], "tags"=>["igf-1r", "phospho", "r1507", "nsclc"], "article_id"=>551553, "categories"=>["Cancer", "Cell Biology"], "users"=>["Yixuan Gong", "Evelyn Yao", "Ronglai Shen", "Aviva Goel", "Maria Arcila", "Julie Teruya-Feldstein", "Maureen F. Zakowski", "Stanley Frankel", "Martin Peifer", "Roman K. Thomas", "Marc Ladanyi", "William Pao"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007273.g002", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Total_IGF_1R_levels_but_not_phospho_IGF_1R_levels_are_associated_with_R1507_sensitivity_in_NSCLC_cells_/551553", "title"=>"Total IGF-1R levels, but not phospho IGF-1R levels, are associated with R1507 sensitivity in NSCLC cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-06 00:25:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/436566", "https://ndownloader.figshare.com/files/436588", "https://ndownloader.figshare.com/files/436601", "https://ndownloader.figshare.com/files/436615"], "description"=>"<div><h3>Background</h3><p>The IGF receptor type 1 (IGF-1R) pathway is frequently deregulated in human tumors and has become a target of interest for anti-cancer therapy.</p><h3>Methodology/Principal Findings</h3><p>We used a panel of 22 non-small cell lung cancer (NSCLC) cell lines to investigate predictive biomarkers of response to R1507, a fully-humanized anti-IGF-1R monoclonal antibody (Ab; Roche). 5 lines were moderately sensitive (25–50% growth inhibition) to R1507 alone. While levels of phospho-IGF-1R did not correlate with drug sensitivity, 4 out of 5 sensitive lines displayed high levels of total IGF-1R versus 1 out of 17 resistant lines (p = 0.003, Fisher's Exact). Sensitive lines also harbored higher copy numbers of <em>IGF-1R</em> as assessed by independent SNP array analysis. Addition of erlotinib or paclitaxel to R1507 led to further growth inhibition in sensitive but not resistant lines. In one <em>EGFR</em> mutant lung adenocarcinoma cell line (11–18), R1507 and erlotinib co-treatment induced apoptosis, whereas treatment with either drug alone induced only cell cycle arrest. Apoptosis was mediated, in part, by the survival-related AKT pathway. Additionally, immunohistochemical (IHC) staining of total IGF-1R with an anti-total IGF-1R Ab (G11;Ventana) was performed on tissue microarrays (TMAs) containing 270 independent NSCLC tumor samples. Staining intensity was scored on a scale of 0 to 3+. 39.3% of tumors showed medium to high IGF-1R IHC staining (scores of 2+ or 3+, respectively), while 16.7% had scores of 3+.</p><h3>Conclusions/Significance</h3><p>In NSCLC cell lines, high levels of total IGF-1R are associated with moderate sensitivity to R1507. These results suggest a possible enrichment strategy for clinical trials with anti-IGF-1R therapy.</p></div>", "links"=>[], "tags"=>["levels", "igf-1r", "nsclc", "cells", "vitro", "anti-igf-1r", "antibody"], "article_id"=>146079, "categories"=>["Cancer", "Cell Biology"], "users"=>["Yixuan Gong", "Evelyn Yao", "Ronglai Shen", "Aviva Goel", "Maria Arcila", "Julie Teruya-Feldstein", "Maureen F. Zakowski", "Stanley Frankel", "Martin Peifer", "Roman K. Thomas", "Marc Ladanyi", "William Pao"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007273.s001", "https://dx.doi.org/10.1371/journal.pone.0007273.s002", "https://dx.doi.org/10.1371/journal.pone.0007273.s003", "https://dx.doi.org/10.1371/journal.pone.0007273.s004"], "stats"=>{"downloads"=>5, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/High_Expression_Levels_of_Total_IGF_1R_and_Sensitivity_of_NSCLC_Cells_In_Vitro_to_an_Anti_IGF_1R_Antibody_R1507_/146079", "title"=>"High Expression Levels of Total IGF-1R and Sensitivity of NSCLC Cells In Vitro to an Anti-IGF-1R Antibody (R1507)", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-10-06 01:41:19"}

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  • {"unique-ip"=>"15", "full-text"=>"16", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
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  • {"unique-ip"=>"18", "full-text"=>"20", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"15", "full-text"=>"13", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
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  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
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  • {"unique-ip"=>"18", "full-text"=>"17", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"15", "full-text"=>"18", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"10", "full-text"=>"14", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"19", "full-text"=>"22", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}

Relative Metric

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