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LC Laboratories ci 1033
ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of <t>CI-1033</t> cytotoxicity.
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Images

1) Product Images from "A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib"

Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

Journal: Biotechnology and bioengineering

doi: 10.1002/bit.23297

ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used:

Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,
Figure Legend Snippet: Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,

Techniques Used:

Ovarian cancer cell lines show different sensitivities to CI-1033
Figure Legend Snippet: Ovarian cancer cell lines show different sensitivities to CI-1033

Techniques Used:

A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that
Figure Legend Snippet: A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that

Techniques Used:

Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.
Figure Legend Snippet: Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.

Techniques Used:

Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used: Expressing

2) Product Images from "A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib"

Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

Journal: Biotechnology and bioengineering

doi: 10.1002/bit.23297

ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used:

Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,
Figure Legend Snippet: Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,

Techniques Used:

Ovarian cancer cell lines show different sensitivities to CI-1033
Figure Legend Snippet: Ovarian cancer cell lines show different sensitivities to CI-1033

Techniques Used:

A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that
Figure Legend Snippet: A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that

Techniques Used:

Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.
Figure Legend Snippet: Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.

Techniques Used:

Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used: Expressing

3) Product Images from "A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib"

Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

Journal: Biotechnology and bioengineering

doi: 10.1002/bit.23297

ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used:

Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,
Figure Legend Snippet: Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,

Techniques Used:

Ovarian cancer cell lines show different sensitivities to CI-1033
Figure Legend Snippet: Ovarian cancer cell lines show different sensitivities to CI-1033

Techniques Used:

A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that
Figure Legend Snippet: A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that

Techniques Used:

Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.
Figure Legend Snippet: Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.

Techniques Used:

Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used: Expressing

4) Product Images from "A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib"

Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

Journal: Biotechnology and bioengineering

doi: 10.1002/bit.23297

ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used:

Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,
Figure Legend Snippet: Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,

Techniques Used:

Ovarian cancer cell lines show different sensitivities to CI-1033
Figure Legend Snippet: Ovarian cancer cell lines show different sensitivities to CI-1033

Techniques Used:

A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that
Figure Legend Snippet: A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that

Techniques Used:

Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.
Figure Legend Snippet: Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.

Techniques Used:

Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used: Expressing

5) Product Images from "A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib"

Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

Journal: Biotechnology and bioengineering

doi: 10.1002/bit.23297

ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used:

Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,
Figure Legend Snippet: Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,

Techniques Used:

Ovarian cancer cell lines show different sensitivities to CI-1033
Figure Legend Snippet: Ovarian cancer cell lines show different sensitivities to CI-1033

Techniques Used:

A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that
Figure Legend Snippet: A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that

Techniques Used:

Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.
Figure Legend Snippet: Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.

Techniques Used:

Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used: Expressing

6) Product Images from "A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib"

Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

Journal: Biotechnology and bioengineering

doi: 10.1002/bit.23297

ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used:

Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,
Figure Legend Snippet: Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,

Techniques Used:

Ovarian cancer cell lines show different sensitivities to CI-1033
Figure Legend Snippet: Ovarian cancer cell lines show different sensitivities to CI-1033

Techniques Used:

A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that
Figure Legend Snippet: A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that

Techniques Used:

Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.
Figure Legend Snippet: Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.

Techniques Used:

Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used: Expressing

7) Product Images from "A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib"

Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

Journal: Biotechnology and bioengineering

doi: 10.1002/bit.23297

ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used:

Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,
Figure Legend Snippet: Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,

Techniques Used:

Ovarian cancer cell lines show different sensitivities to CI-1033
Figure Legend Snippet: Ovarian cancer cell lines show different sensitivities to CI-1033

Techniques Used:

A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that
Figure Legend Snippet: A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that

Techniques Used:

Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.
Figure Legend Snippet: Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.

Techniques Used:

Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used: Expressing

8) Product Images from "A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib"

Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

Journal: Biotechnology and bioengineering

doi: 10.1002/bit.23297

ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used:

Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,
Figure Legend Snippet: Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,

Techniques Used:

Ovarian cancer cell lines show different sensitivities to CI-1033
Figure Legend Snippet: Ovarian cancer cell lines show different sensitivities to CI-1033

Techniques Used:

A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that
Figure Legend Snippet: A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that

Techniques Used:

Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.
Figure Legend Snippet: Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.

Techniques Used:

Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used: Expressing

9) Product Images from "A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib"

Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

Journal: Biotechnology and bioengineering

doi: 10.1002/bit.23297

ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used:

Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,
Figure Legend Snippet: Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,

Techniques Used:

Ovarian cancer cell lines show different sensitivities to CI-1033
Figure Legend Snippet: Ovarian cancer cell lines show different sensitivities to CI-1033

Techniques Used:

A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that
Figure Legend Snippet: A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that

Techniques Used:

Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.
Figure Legend Snippet: Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.

Techniques Used:

Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used: Expressing

10) Product Images from "Inhibition of Oncogenic Epidermal Growth Factor Receptor Kinase Triggers Release of Exosome-like Extracellular Vesicles and Impacts Their Phosphoprotein and DNA Content *"

Article Title: Inhibition of Oncogenic Epidermal Growth Factor Receptor Kinase Triggers Release of Exosome-like Extracellular Vesicles and Impacts Their Phosphoprotein and DNA Content *

Journal: The Journal of Biological Chemistry

doi: 10.1074/jbc.M115.679217

EV-mediated extracellular co-emission of EGFR and DNA following cancer cell exposure to EKIs. A, experimental design: ImmunoCapture of pre-filtered, EGFR-containing EVs produced by A431 cells either in the absence of in the presence of EKIs, followed by detection of extracellular genomic DNA (exo-gDNA; PCR). B, analysis of EGFR genomic sequences in EV fractions captured on plates coated with anti-EGFR antibody. This assay reveals that the same population of small EGFR-positive exosome-like EVs, which are able to pass through both 0.8- and 0.45-μm filters, is enriched in exo-gDNA, but only if the cells were pretreated with growth inhibitory doses of EKIs, CI-1033 or PF-00299804 (see text for details). UC , ultracentrifugation; -, possible but not obligatory step in the procedure.
Figure Legend Snippet: EV-mediated extracellular co-emission of EGFR and DNA following cancer cell exposure to EKIs. A, experimental design: ImmunoCapture of pre-filtered, EGFR-containing EVs produced by A431 cells either in the absence of in the presence of EKIs, followed by detection of extracellular genomic DNA (exo-gDNA; PCR). B, analysis of EGFR genomic sequences in EV fractions captured on plates coated with anti-EGFR antibody. This assay reveals that the same population of small EGFR-positive exosome-like EVs, which are able to pass through both 0.8- and 0.45-μm filters, is enriched in exo-gDNA, but only if the cells were pretreated with growth inhibitory doses of EKIs, CI-1033 or PF-00299804 (see text for details). UC , ultracentrifugation; -, possible but not obligatory step in the procedure.

Techniques Used: Produced, Polymerase Chain Reaction, Genomic Sequencing

EKI-induced cellular vesiculation depends on the neutral sphingomyelinase pathway of exosomal biogenesis. A, NTA analysis of EVs emitted from A431 cells treated with EKI (CI-1033 ( CI )), inhibitor of neutral sphingomyelinase (GW4869), inhibitor of acidic sphingomyelinase (FTY720), or their indicated combinations. Of note is a shift to the right in the median size peak of EVs in presence of GW4869 indicative of reduced numbers of exosome-seized vesicles and the preponderance of larger EV sizes. B, EV output into the A431 conditioned medium as measured within the median exosome size (range 150–200 nm) of vesicles. CI-1033-induced increase in EV numbers is attenuated by GW4869 pretreatment but not by FTY720 pretreatment, which increases the EV production; compilation is of three independent experiments, and p value is as indicated. NS , nonsignificant.
Figure Legend Snippet: EKI-induced cellular vesiculation depends on the neutral sphingomyelinase pathway of exosomal biogenesis. A, NTA analysis of EVs emitted from A431 cells treated with EKI (CI-1033 ( CI )), inhibitor of neutral sphingomyelinase (GW4869), inhibitor of acidic sphingomyelinase (FTY720), or their indicated combinations. Of note is a shift to the right in the median size peak of EVs in presence of GW4869 indicative of reduced numbers of exosome-seized vesicles and the preponderance of larger EV sizes. B, EV output into the A431 conditioned medium as measured within the median exosome size (range 150–200 nm) of vesicles. CI-1033-induced increase in EV numbers is attenuated by GW4869 pretreatment but not by FTY720 pretreatment, which increases the EV production; compilation is of three independent experiments, and p value is as indicated. NS , nonsignificant.

Techniques Used:

Responses of EGFR-driven cancer cells to EGFR inhibitors. A–C, A431 cells harboring genomic amplification of the EGFR gene were grown in monolayer cultures and exposed for 24 h to the indicated irreversible EGFR kinase inhibitors (EKIs: CI-1033 and PF-00299804) or neutralizing anti-EGFR antibody (Cetuximab) at increasing concentrations. The cells were tested for metabolic activity using the MTS assay. EKIs, but not Cetuximab, triggered marked and dose-dependent reduction in metabolic activity. D, effects of drug treatment on EGFR phosphorylation ( P-EGFR ; Western blotting); numerical values represent mean ± S.D. of several independent experiments; *, p > 0.05.
Figure Legend Snippet: Responses of EGFR-driven cancer cells to EGFR inhibitors. A–C, A431 cells harboring genomic amplification of the EGFR gene were grown in monolayer cultures and exposed for 24 h to the indicated irreversible EGFR kinase inhibitors (EKIs: CI-1033 and PF-00299804) or neutralizing anti-EGFR antibody (Cetuximab) at increasing concentrations. The cells were tested for metabolic activity using the MTS assay. EKIs, but not Cetuximab, triggered marked and dose-dependent reduction in metabolic activity. D, effects of drug treatment on EGFR phosphorylation ( P-EGFR ; Western blotting); numerical values represent mean ± S.D. of several independent experiments; *, p > 0.05.

Techniques Used: Amplification, Activity Assay, MTS Assay, Western Blot

11) Product Images from "A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib"

Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

Journal: Biotechnology and bioengineering

doi: 10.1002/bit.23297

ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used:

Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,
Figure Legend Snippet: Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,

Techniques Used:

Ovarian cancer cell lines show different sensitivities to CI-1033
Figure Legend Snippet: Ovarian cancer cell lines show different sensitivities to CI-1033

Techniques Used:

A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that
Figure Legend Snippet: A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that

Techniques Used:

Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.
Figure Legend Snippet: Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.

Techniques Used:

Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used: Expressing

12) Product Images from "A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib"

Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

Journal: Biotechnology and bioengineering

doi: 10.1002/bit.23297

ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used:

Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,
Figure Legend Snippet: Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,

Techniques Used:

Ovarian cancer cell lines show different sensitivities to CI-1033
Figure Legend Snippet: Ovarian cancer cell lines show different sensitivities to CI-1033

Techniques Used:

A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that
Figure Legend Snippet: A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that

Techniques Used:

Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.
Figure Legend Snippet: Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.

Techniques Used:

Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used: Expressing

13) Product Images from "A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib"

Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

Journal: Biotechnology and bioengineering

doi: 10.1002/bit.23297

ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used:

Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,
Figure Legend Snippet: Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,

Techniques Used:

Ovarian cancer cell lines show different sensitivities to CI-1033
Figure Legend Snippet: Ovarian cancer cell lines show different sensitivities to CI-1033

Techniques Used:

A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that
Figure Legend Snippet: A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that

Techniques Used:

Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.
Figure Legend Snippet: Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.

Techniques Used:

Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used: Expressing

14) Product Images from "A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib"

Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

Journal: Biotechnology and bioengineering

doi: 10.1002/bit.23297

ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used:

Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,
Figure Legend Snippet: Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,

Techniques Used:

Ovarian cancer cell lines show different sensitivities to CI-1033
Figure Legend Snippet: Ovarian cancer cell lines show different sensitivities to CI-1033

Techniques Used:

A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that
Figure Legend Snippet: A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that

Techniques Used:

Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.
Figure Legend Snippet: Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.

Techniques Used:

Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used: Expressing

15) Product Images from "A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib"

Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

Journal: Biotechnology and bioengineering

doi: 10.1002/bit.23297

ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used:

Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,
Figure Legend Snippet: Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,

Techniques Used:

Ovarian cancer cell lines show different sensitivities to CI-1033
Figure Legend Snippet: Ovarian cancer cell lines show different sensitivities to CI-1033

Techniques Used:

A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that
Figure Legend Snippet: A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that

Techniques Used:

Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.
Figure Legend Snippet: Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.

Techniques Used:

Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.
Figure Legend Snippet: Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

Techniques Used: Expressing

Related Articles

Produced:

Article Title: Antibody-assisted target identification reveals afatinib, an EGFR covalent inhibitor, down-regulating ribonucleotide reductase
Article Snippet: .. Gemcitabine, propidium iodide, anti-RRM1, anti-RRM2 (Santa Cruz Biotechnology, Inc., Dallas, TX); DMEM, RPMI 1649 medium, fetal bovine serum (HyClone Laboratories, Inc., South Logan, UT); human RRM1 and RRM2 produced from HEK293 cells (OriGene Technologies, Inc., Rockville, MD); anti-EGFR, anti-GAPDH, DNA damage antibody sampler kit (Cell Signaling Technology, Boston, MA); C18 Zip-tip, Amicon Ultra-15 centrifugal filters, anti-phospho-Histone H2AX (Ser 139) (α-γ-H2AX) (Merck Millipore, Darmstadt, Germany); protein A-sepharose fast flow (GE Healthcare, Chicago, IL ); afatinib, canertinib, dacomitinib, neratinib, erlotinib (LC Laboratories, Woburn, MA) were purchased from manufacturers indicated in parentheses. ..

Western Blot:

Article Title: Growth-Factor-Driven Rescue to Receptor Tyrosine Kinase (RTK) Inhibitors through Akt and Erk Phosphorylation in Pediatric Low Grade Astrocytoma and Ependymoma
Article Snippet: .. Western blot analyses 1 x 106 cells were seeded in T25 flasks in 5 ml DMEM-F12 containing 1% FCS to which after adhesion sorafenib 8 uM, dasatinib 1 uM, canertinib 8 uM or crizotinib 9 uM (LC laboratories) was added. .. In the combination treatments, the second inhibitor was added at a lower concentration: sorafenib 2 uM, canertinib 4 uM or crizotinib 3 uM.

Flow Cytometry:

Article Title: Antibody-assisted target identification reveals afatinib, an EGFR covalent inhibitor, down-regulating ribonucleotide reductase
Article Snippet: .. Gemcitabine, propidium iodide, anti-RRM1, anti-RRM2 (Santa Cruz Biotechnology, Inc., Dallas, TX); DMEM, RPMI 1649 medium, fetal bovine serum (HyClone Laboratories, Inc., South Logan, UT); human RRM1 and RRM2 produced from HEK293 cells (OriGene Technologies, Inc., Rockville, MD); anti-EGFR, anti-GAPDH, DNA damage antibody sampler kit (Cell Signaling Technology, Boston, MA); C18 Zip-tip, Amicon Ultra-15 centrifugal filters, anti-phospho-Histone H2AX (Ser 139) (α-γ-H2AX) (Merck Millipore, Darmstadt, Germany); protein A-sepharose fast flow (GE Healthcare, Chicago, IL ); afatinib, canertinib, dacomitinib, neratinib, erlotinib (LC Laboratories, Woburn, MA) were purchased from manufacturers indicated in parentheses. ..

other:

Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib
Article Snippet: To determine responsiveness toward CI-1033 a dose-response cytotoxicity curve was built for each cell line in the panel and fit by a four-parameters logistic curve.

Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib
Article Snippet: We next evaluated the model’s ability to predict sensitivity to CI-1033 for cell lines that were not included as a part of the training set to determine if the model was broadly applicable.

Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib
Article Snippet: To our knowledge, the sensitivity of these cell lines to CI-1033 has not been reported.

Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib
Article Snippet: In addition, using this measure of sensitivity toward CI-1033, we were able to take into account the unique baseline level of cell death due to serum starvation of each cell line. shows two representative dose-response curves for an insensitive cell line (OVCAR5) and a sensitive cell line (OVCA433), while all fitted parameters values are presented in .

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    LC Laboratories ci 1033
    ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of <t>CI-1033</t> cytotoxicity.
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    ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

    Journal: Biotechnology and bioengineering

    Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

    doi: 10.1002/bit.23297

    Figure Lengend Snippet: ErbB autocrine ligands in the EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

    Article Snippet: To our knowledge, the sensitivity of these cell lines to CI-1033 has not been reported.

    Techniques:

    Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,

    Journal: Biotechnology and bioengineering

    Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

    doi: 10.1002/bit.23297

    Figure Lengend Snippet: Top nine reduced models. ( A ) Subsets of proteins used in the top nine models, shaded box indicates the protein was included in the X matrix. ( B ) Representative predictions of a reduced CI-1033 cytotoxicity model (X matrix composed of ErbB1, NRG1-β,

    Article Snippet: To our knowledge, the sensitivity of these cell lines to CI-1033 has not been reported.

    Techniques:

    Ovarian cancer cell lines show different sensitivities to CI-1033

    Journal: Biotechnology and bioengineering

    Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

    doi: 10.1002/bit.23297

    Figure Lengend Snippet: Ovarian cancer cell lines show different sensitivities to CI-1033

    Article Snippet: To our knowledge, the sensitivity of these cell lines to CI-1033 has not been reported.

    Techniques:

    A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that

    Journal: Biotechnology and bioengineering

    Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

    doi: 10.1002/bit.23297

    Figure Lengend Snippet: A multi-protein model is needed to predict cell line cytotoxicity to CI-1033. ( A ) Full PLSR model of CI-1033 cytotoxicity, and ( B ) reduced CI-1033 cytotoxicity models built using subsets of proteins. N/A indicates inability to build a model using that

    Article Snippet: To our knowledge, the sensitivity of these cell lines to CI-1033 has not been reported.

    Techniques:

    Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.

    Journal: Biotechnology and bioengineering

    Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

    doi: 10.1002/bit.23297

    Figure Lengend Snippet: Representative CI-1033 cytotoxicity dose-response curves. ( A ) OVCAR5, ( B ) OVCA433.

    Article Snippet: To our knowledge, the sensitivity of these cell lines to CI-1033 has not been reported.

    Techniques:

    Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

    Journal: Biotechnology and bioengineering

    Article Title: A Multivariate Model of ErbB Network Composition Predicts Ovarian Cancer Cell Response to Canertinib

    doi: 10.1002/bit.23297

    Figure Lengend Snippet: Expression of ErbB1-4 in EOC cell lines in the prediction set. The grey box represents the data range included in the original full PLSR model of CI-1033 cytotoxicity.

    Article Snippet: To our knowledge, the sensitivity of these cell lines to CI-1033 has not been reported.

    Techniques: Expressing

    Growth factors overcome RTK-inhibited-phosphorylation of downstream targets. Examples of immunoblots showing effects of growth factors (100 ng/ml) on Akt and Erk phosphorylation (p) after sorafenib ( A ), dasatinib ( B ), canertinib ( C ), crizotinib ( D ) in pediatric low grade astrocytoma and ependymoma cells (2h). Controls represent the specific cell lines treated with DMSO. Growth-factor-driven rescue on cell viability as given in Fig. 3C and D is indicated underneath the blots: purple squares, no rescue; yellow/orange squares, partial rescue; red squares, complete rescue. Protein expression was normalized to β-actin as loading control and derived from three independent experiments of which the mean (± SEM) was calculated. EGF and HGF-driven rescue resulted in significantly higher protein expression of Akt (p = 0.028) and Erk (p = 0.043) during sorafenib in both UW-467 and Res-196 cells and during dasatinib in the low grade astrocytoma cell lines (p = 0.028 and p = 0.043). Significantly higher Akt phosphorylation was found after HGF addition during canertinib in Res-186, Res-259 and Res-196 cells (p = 0.043) of which Res-186 is shown as an example. *Discrepancies between growth-factor-driven rescue on cell viability level and downstream phosphorylation status.

    Journal: PLoS ONE

    Article Title: Growth-Factor-Driven Rescue to Receptor Tyrosine Kinase (RTK) Inhibitors through Akt and Erk Phosphorylation in Pediatric Low Grade Astrocytoma and Ependymoma

    doi: 10.1371/journal.pone.0122555

    Figure Lengend Snippet: Growth factors overcome RTK-inhibited-phosphorylation of downstream targets. Examples of immunoblots showing effects of growth factors (100 ng/ml) on Akt and Erk phosphorylation (p) after sorafenib ( A ), dasatinib ( B ), canertinib ( C ), crizotinib ( D ) in pediatric low grade astrocytoma and ependymoma cells (2h). Controls represent the specific cell lines treated with DMSO. Growth-factor-driven rescue on cell viability as given in Fig. 3C and D is indicated underneath the blots: purple squares, no rescue; yellow/orange squares, partial rescue; red squares, complete rescue. Protein expression was normalized to β-actin as loading control and derived from three independent experiments of which the mean (± SEM) was calculated. EGF and HGF-driven rescue resulted in significantly higher protein expression of Akt (p = 0.028) and Erk (p = 0.043) during sorafenib in both UW-467 and Res-196 cells and during dasatinib in the low grade astrocytoma cell lines (p = 0.028 and p = 0.043). Significantly higher Akt phosphorylation was found after HGF addition during canertinib in Res-186, Res-259 and Res-196 cells (p = 0.043) of which Res-186 is shown as an example. *Discrepancies between growth-factor-driven rescue on cell viability level and downstream phosphorylation status.

    Article Snippet: Western blot analyses 1 x 106 cells were seeded in T25 flasks in 5 ml DMEM-F12 containing 1% FCS to which after adhesion sorafenib 8 uM, dasatinib 1 uM, canertinib 8 uM or crizotinib 9 uM (LC laboratories) was added.

    Techniques: Western Blot, Expressing, Derivative Assay

    RTK signaling pathways. Schematic illustration showing important growth factors in brain tumors that can bind RTKs activating downstream pathways which contributes to tumor cell survival. These potential drugable targets can be inhibited by e . g . sorafenib, dasatinib, canertinib and crizotinib.

    Journal: PLoS ONE

    Article Title: Growth-Factor-Driven Rescue to Receptor Tyrosine Kinase (RTK) Inhibitors through Akt and Erk Phosphorylation in Pediatric Low Grade Astrocytoma and Ependymoma

    doi: 10.1371/journal.pone.0122555

    Figure Lengend Snippet: RTK signaling pathways. Schematic illustration showing important growth factors in brain tumors that can bind RTKs activating downstream pathways which contributes to tumor cell survival. These potential drugable targets can be inhibited by e . g . sorafenib, dasatinib, canertinib and crizotinib.

    Article Snippet: Western blot analyses 1 x 106 cells were seeded in T25 flasks in 5 ml DMEM-F12 containing 1% FCS to which after adhesion sorafenib 8 uM, dasatinib 1 uM, canertinib 8 uM or crizotinib 9 uM (LC laboratories) was added.

    Techniques:

    Combined RTK treatment can overcome growth-factor-driven rescue. Cell viability assays demonstrating additional effects of combination treatment in pediatric low grade astrocytoma (Res-259) and ependymoma (Res-196) compared with single treatment (mean ± SD, 48h). Immunoblots showing effect of single RTK inhibition (8 uM), the rescue effect of growth factors (100 ng/ml) and the ability of the second inhibitor (canertinib 4 uM, crizotinib 3 uM, sorafenib 2 uM) to overcome this growth-factor-driven rescue on Akt and Erk phosphorylation (p) in pediatric low grade astrocytoma and ependymoma cells (2h). Protein expression was normalized to β-actin as loading control and derived from three independent experiments of which the mean (± SEM) was calculated. The ability of crizotinib to overcome HGF-driven rescue during canertinib treatment reached statistical significance on Akt and Erk phosphorylation (p = 0.028 and p = 0.046 respectively).

    Journal: PLoS ONE

    Article Title: Growth-Factor-Driven Rescue to Receptor Tyrosine Kinase (RTK) Inhibitors through Akt and Erk Phosphorylation in Pediatric Low Grade Astrocytoma and Ependymoma

    doi: 10.1371/journal.pone.0122555

    Figure Lengend Snippet: Combined RTK treatment can overcome growth-factor-driven rescue. Cell viability assays demonstrating additional effects of combination treatment in pediatric low grade astrocytoma (Res-259) and ependymoma (Res-196) compared with single treatment (mean ± SD, 48h). Immunoblots showing effect of single RTK inhibition (8 uM), the rescue effect of growth factors (100 ng/ml) and the ability of the second inhibitor (canertinib 4 uM, crizotinib 3 uM, sorafenib 2 uM) to overcome this growth-factor-driven rescue on Akt and Erk phosphorylation (p) in pediatric low grade astrocytoma and ependymoma cells (2h). Protein expression was normalized to β-actin as loading control and derived from three independent experiments of which the mean (± SEM) was calculated. The ability of crizotinib to overcome HGF-driven rescue during canertinib treatment reached statistical significance on Akt and Erk phosphorylation (p = 0.028 and p = 0.046 respectively).

    Article Snippet: Western blot analyses 1 x 106 cells were seeded in T25 flasks in 5 ml DMEM-F12 containing 1% FCS to which after adhesion sorafenib 8 uM, dasatinib 1 uM, canertinib 8 uM or crizotinib 9 uM (LC laboratories) was added.

    Techniques: Western Blot, Inhibition, Expressing, Derivative Assay

    Tumor cell migration. Cell monolayers were scratched with a pipette tip to produce a clear cell-free area into which cells at the periphery could migrate. Micrographs showing migrated Res-259 cells treated with DMSO (control), the effect on tumor cell migration of HGF (100 ng/ml), canertinib (2 uM), HGF addition to canertinib and the combination treatment including canertinib and crizotinib (3 uM) after 24h (upper panels) and 48h (lower panels).

    Journal: PLoS ONE

    Article Title: Growth-Factor-Driven Rescue to Receptor Tyrosine Kinase (RTK) Inhibitors through Akt and Erk Phosphorylation in Pediatric Low Grade Astrocytoma and Ependymoma

    doi: 10.1371/journal.pone.0122555

    Figure Lengend Snippet: Tumor cell migration. Cell monolayers were scratched with a pipette tip to produce a clear cell-free area into which cells at the periphery could migrate. Micrographs showing migrated Res-259 cells treated with DMSO (control), the effect on tumor cell migration of HGF (100 ng/ml), canertinib (2 uM), HGF addition to canertinib and the combination treatment including canertinib and crizotinib (3 uM) after 24h (upper panels) and 48h (lower panels).

    Article Snippet: Western blot analyses 1 x 106 cells were seeded in T25 flasks in 5 ml DMEM-F12 containing 1% FCS to which after adhesion sorafenib 8 uM, dasatinib 1 uM, canertinib 8 uM or crizotinib 9 uM (LC laboratories) was added.

    Techniques: Migration, Transferring

    RTK expression and inhibition. A , Heat map showing percentages of cells expressing numerous growth factor receptors above control levels using flow cytometry analyses in pediatric low grade astrocytoma (Res-186, Res-259, UW-467) and ependymoma (Res-196) cell lines. B , Cell viability assays demonstrating the mean effect ± SD of sorafenib, dasatinib, canertinib and crizotinib on pediatric low grade astrocytoma (Res-186, Res-259, UW-467) and ependymoma (Res-196) cell lines after 48h.

    Journal: PLoS ONE

    Article Title: Growth-Factor-Driven Rescue to Receptor Tyrosine Kinase (RTK) Inhibitors through Akt and Erk Phosphorylation in Pediatric Low Grade Astrocytoma and Ependymoma

    doi: 10.1371/journal.pone.0122555

    Figure Lengend Snippet: RTK expression and inhibition. A , Heat map showing percentages of cells expressing numerous growth factor receptors above control levels using flow cytometry analyses in pediatric low grade astrocytoma (Res-186, Res-259, UW-467) and ependymoma (Res-196) cell lines. B , Cell viability assays demonstrating the mean effect ± SD of sorafenib, dasatinib, canertinib and crizotinib on pediatric low grade astrocytoma (Res-186, Res-259, UW-467) and ependymoma (Res-196) cell lines after 48h.

    Article Snippet: Western blot analyses 1 x 106 cells were seeded in T25 flasks in 5 ml DMEM-F12 containing 1% FCS to which after adhesion sorafenib 8 uM, dasatinib 1 uM, canertinib 8 uM or crizotinib 9 uM (LC laboratories) was added.

    Techniques: Expressing, Inhibition, Flow Cytometry, Cytometry