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James C Willey - One of the best experts on this subject based on the ideXlab platform.

  • ABCC5 ercc2 xpa and xrcc1 transcript abundance levels correlate with cisplatin chemoresistance in non small cell lung cancer cell lines
    Molecular Cancer, 2005
    Co-Authors: David A Weaver, Kristy A Warner, Fadel Elkhairi, Erin L. Crawford, Sadik A. Khuder, James C Willey
    Abstract:

    Background Although 40–50% of non-small cell lung cancer (NSCLC) tumors respond to cisplatin chemotherapy, there currently is no way to prospectively identify potential responders. The purpose of this study was to determine whether transcript abundance (TA) levels of twelve selected DNA repair or multi-drug resistance genes (LIG1, ERCC2, ERCC3, DDIT3, ABCC1, ABCC4, ABCC5, ABCC10, GTF2H2, XPA, XPC and XRCC1) were associated with cisplatin chemoresistance and could therefore contribute to the development of a predictive marker. Standardized RT (StaRT)-PCR, was employed to assess these genes in a set of NSCLC cell lines with a previously published range of sensitivity to cisplatin. Data were obtained in the form of target gene molecules relative to 106 β-actin (ACTB) molecules. To cancel the effect of ACTB variation among the different cell lines individual gene expression values were incorporated into ratios of one gene to another. Each two-gene ratio was compared as a single variable to chemoresistance for each of eight NSCLC cell lines using multiple regression. In an effort to validate these results, six additional lines then were evaluated.

  • ABCC5, ERCC2, XPA and XRCC1 transcript abundance levels correlate with cisplatin chemoresistance in non-small cell lung cancer cell lines
    Molecular Cancer, 2005
    Co-Authors: David A Weaver, Kristy A Warner, Fadel Elkhairi, Erin L. Crawford, Sadik A. Khuder, James C Willey
    Abstract:

    Background Although 40–50% of non-small cell lung cancer (NSCLC) tumors respond to cisplatin chemotherapy, there currently is no way to prospectively identify potential responders. The purpose of this study was to determine whether transcript abundance (TA) levels of twelve selected DNA repair or multi-drug resistance genes ( LIG1 , ERCC2 , ERCC3 , DDIT3 , ABCC1 , ABCC4 , ABCC5 , ABCC10 , GTF2H2 , XPA , XPC and XRCC1 ) were associated with cisplatin chemoresistance and could therefore contribute to the development of a predictive marker. Standardized RT (StaRT)-PCR, was employed to assess these genes in a set of NSCLC cell lines with a previously published range of sensitivity to cisplatin. Data were obtained in the form of target gene molecules relative to 10^6 β-actin ( ACTB ) molecules. To cancel the effect of ACTB variation among the different cell lines individual gene expression values were incorporated into ratios of one gene to another. Each two-gene ratio was compared as a single variable to chemoresistance for each of eight NSCLC cell lines using multiple regression. In an effort to validate these results, six additional lines then were evaluated. Results Following validation, single variable models best correlated with chemoresistance (p < 0.001), were ERCC2/XPC , ABCC5/GTF2H2 , ERCC2/GTF2H2 , XPA/XPC and XRCC1/XPC . All single variable models were examined hierarchically to achieve two variable models. The two variable model with the highest correlation was ( ABCC5/GTF2H2 , ERCC2/GTF2H2 ) with an R^2 value of 0.96 (p < 0.001). Conclusion These results provide markers suitable for assessment of small fine needle aspirate biopsies in an effort to prospectively identify cisplatin resistant tumors.

David A Weaver - One of the best experts on this subject based on the ideXlab platform.

  • ABCC5 ercc2 xpa and xrcc1 transcript abundance levels correlate with cisplatin chemoresistance in non small cell lung cancer cell lines
    Molecular Cancer, 2005
    Co-Authors: David A Weaver, Kristy A Warner, Fadel Elkhairi, Erin L. Crawford, Sadik A. Khuder, James C Willey
    Abstract:

    Background Although 40–50% of non-small cell lung cancer (NSCLC) tumors respond to cisplatin chemotherapy, there currently is no way to prospectively identify potential responders. The purpose of this study was to determine whether transcript abundance (TA) levels of twelve selected DNA repair or multi-drug resistance genes (LIG1, ERCC2, ERCC3, DDIT3, ABCC1, ABCC4, ABCC5, ABCC10, GTF2H2, XPA, XPC and XRCC1) were associated with cisplatin chemoresistance and could therefore contribute to the development of a predictive marker. Standardized RT (StaRT)-PCR, was employed to assess these genes in a set of NSCLC cell lines with a previously published range of sensitivity to cisplatin. Data were obtained in the form of target gene molecules relative to 106 β-actin (ACTB) molecules. To cancel the effect of ACTB variation among the different cell lines individual gene expression values were incorporated into ratios of one gene to another. Each two-gene ratio was compared as a single variable to chemoresistance for each of eight NSCLC cell lines using multiple regression. In an effort to validate these results, six additional lines then were evaluated.

  • ABCC5, ERCC2, XPA and XRCC1 transcript abundance levels correlate with cisplatin chemoresistance in non-small cell lung cancer cell lines
    Molecular Cancer, 2005
    Co-Authors: David A Weaver, Kristy A Warner, Fadel Elkhairi, Erin L. Crawford, Sadik A. Khuder, James C Willey
    Abstract:

    Background Although 40–50% of non-small cell lung cancer (NSCLC) tumors respond to cisplatin chemotherapy, there currently is no way to prospectively identify potential responders. The purpose of this study was to determine whether transcript abundance (TA) levels of twelve selected DNA repair or multi-drug resistance genes ( LIG1 , ERCC2 , ERCC3 , DDIT3 , ABCC1 , ABCC4 , ABCC5 , ABCC10 , GTF2H2 , XPA , XPC and XRCC1 ) were associated with cisplatin chemoresistance and could therefore contribute to the development of a predictive marker. Standardized RT (StaRT)-PCR, was employed to assess these genes in a set of NSCLC cell lines with a previously published range of sensitivity to cisplatin. Data were obtained in the form of target gene molecules relative to 10^6 β-actin ( ACTB ) molecules. To cancel the effect of ACTB variation among the different cell lines individual gene expression values were incorporated into ratios of one gene to another. Each two-gene ratio was compared as a single variable to chemoresistance for each of eight NSCLC cell lines using multiple regression. In an effort to validate these results, six additional lines then were evaluated. Results Following validation, single variable models best correlated with chemoresistance (p < 0.001), were ERCC2/XPC , ABCC5/GTF2H2 , ERCC2/GTF2H2 , XPA/XPC and XRCC1/XPC . All single variable models were examined hierarchically to achieve two variable models. The two variable model with the highest correlation was ( ABCC5/GTF2H2 , ERCC2/GTF2H2 ) with an R^2 value of 0.96 (p < 0.001). Conclusion These results provide markers suitable for assessment of small fine needle aspirate biopsies in an effort to prospectively identify cisplatin resistant tumors.

Pavlina Konstantinova - One of the best experts on this subject based on the ideXlab platform.

  • adenosine triphosphate binding cassette transporter genes up regulation in untreated hepatocellular carcinoma is mediated by cellular micrornas
    Hepatology, 2012
    Co-Authors: Florie Borel, Allerdien Visser, Harald Petry, Sander Van Deventer, Peter L M Jansen, Pavlina Konstantinova
    Abstract:

    Adenosine triphosphate (ATP)-binding cassette (ABC) transporters are drug efflux pumps responsible for the multidrug resistance phenotype causing hepatocellular carcinoma (HCC) treatment failure. Here we studied the expression of 15 ABC transporters relevant for multidrug resistance in 19 paired HCC patient samples (16 untreated, 3 treated by chemotherapeutics). Twelve ABC transporters showed up-regulation in HCC compared with adjacent healthy liver. These include ABCA2, ABCB1, ABCB6, ABCC1, ABCC2, ABCC3, ABCC4, ABCC5, ABCC10, ABCC11, ABCC12, and ABCE1. The expression profile and function of some of these transporters have not been associated with HCC thus far. Because cellular microRNAs (miRNAs) are involved in posttranscriptional gene silencing, we hypothesized that regulation of ABC expression in HCC might be mediated by miRNAs. To study this, miRNAs were profiled and dysregulation of 90 miRNAs was shown in HCC compared with healthy liver, including up-regulation of 11 and down-regulation of 79. miRNA target sites in ABC genes were bioinformatically predicted and experimentally verified in vitro using luciferase reporter assays. In total, 13 cellular miRNAs were confirmed that target ABCA1, ABCC1, ABCC5, ABCC10, and ABCE1 genes and mediate changes in gene expression. Correlation analysis between ABC and miRNA expression in individual patients revealed an inverse relationship, providing an indication for miRNA regulation of ABC genes in HCC. Conclusion: Up-regulation of ABC transporters in HCC occurs prior to chemotherapeutic treatment and is associated with miRNA down-regulation. Up-regulation of five ABC genes appears to be mediated by 13 cellular miRNAs in HCC patient samples. miRNA-based gene therapy may be a novel and promising way to affect the ABC profile and overcome clinical multidrug resistance. (Hepatology 2012)

  • Adenosine triphosphate‐binding cassette transporter genes up‐regulation in untreated hepatocellular carcinoma is mediated by cellular microRNAs
    Hepatology, 2012
    Co-Authors: Florie Borel, Allerdien Visser, Harald Petry, Peter L M Jansen, Ruiqi Han, Sander J. H. Van Deventer, Pavlina Konstantinova
    Abstract:

    Adenosine triphosphate (ATP)-binding cassette (ABC) transporters are drug efflux pumps responsible for the multidrug resistance phenotype causing hepatocellular carcinoma (HCC) treatment failure. Here we studied the expression of 15 ABC transporters relevant for multidrug resistance in 19 paired HCC patient samples (16 untreated, 3 treated by chemotherapeutics). Twelve ABC transporters showed up-regulation in HCC compared with adjacent healthy liver. These include ABCA2, ABCB1, ABCB6, ABCC1, ABCC2, ABCC3, ABCC4, ABCC5, ABCC10, ABCC11, ABCC12, and ABCE1. The expression profile and function of some of these transporters have not been associated with HCC thus far. Because cellular microRNAs (miRNAs) are involved in posttranscriptional gene silencing, we hypothesized that regulation of ABC expression in HCC might be mediated by miRNAs. To study this, miRNAs were profiled and dysregulation of 90 miRNAs was shown in HCC compared with healthy liver, including up-regulation of 11 and down-regulation of 79. miRNA target sites in ABC genes were bioinformatically predicted and experimentally verified in vitro using luciferase reporter assays. In total, 13 cellular miRNAs were confirmed that target ABCA1, ABCC1, ABCC5, ABCC10, and ABCE1 genes and mediate changes in gene expression. Correlation analysis between ABC and miRNA expression in individual patients revealed an inverse relationship, providing an indication for miRNA regulation of ABC genes in HCC. Conclusion: Up-regulation of ABC transporters in HCC occurs prior to chemotherapeutic treatment and is associated with miRNA down-regulation. Up-regulation of five ABC genes appears to be mediated by 13 cellular miRNAs in HCC patient samples. miRNA-based gene therapy may be a novel and promising way to affect the ABC profile and overcome clinical multidrug resistance. (Hepatology 2012)

Kristy A Warner - One of the best experts on this subject based on the ideXlab platform.

  • ABCC5 ercc2 xpa and xrcc1 transcript abundance levels correlate with cisplatin chemoresistance in non small cell lung cancer cell lines
    Molecular Cancer, 2005
    Co-Authors: David A Weaver, Kristy A Warner, Fadel Elkhairi, Erin L. Crawford, Sadik A. Khuder, James C Willey
    Abstract:

    Background Although 40–50% of non-small cell lung cancer (NSCLC) tumors respond to cisplatin chemotherapy, there currently is no way to prospectively identify potential responders. The purpose of this study was to determine whether transcript abundance (TA) levels of twelve selected DNA repair or multi-drug resistance genes (LIG1, ERCC2, ERCC3, DDIT3, ABCC1, ABCC4, ABCC5, ABCC10, GTF2H2, XPA, XPC and XRCC1) were associated with cisplatin chemoresistance and could therefore contribute to the development of a predictive marker. Standardized RT (StaRT)-PCR, was employed to assess these genes in a set of NSCLC cell lines with a previously published range of sensitivity to cisplatin. Data were obtained in the form of target gene molecules relative to 106 β-actin (ACTB) molecules. To cancel the effect of ACTB variation among the different cell lines individual gene expression values were incorporated into ratios of one gene to another. Each two-gene ratio was compared as a single variable to chemoresistance for each of eight NSCLC cell lines using multiple regression. In an effort to validate these results, six additional lines then were evaluated.

  • ABCC5, ERCC2, XPA and XRCC1 transcript abundance levels correlate with cisplatin chemoresistance in non-small cell lung cancer cell lines
    Molecular Cancer, 2005
    Co-Authors: David A Weaver, Kristy A Warner, Fadel Elkhairi, Erin L. Crawford, Sadik A. Khuder, James C Willey
    Abstract:

    Background Although 40–50% of non-small cell lung cancer (NSCLC) tumors respond to cisplatin chemotherapy, there currently is no way to prospectively identify potential responders. The purpose of this study was to determine whether transcript abundance (TA) levels of twelve selected DNA repair or multi-drug resistance genes ( LIG1 , ERCC2 , ERCC3 , DDIT3 , ABCC1 , ABCC4 , ABCC5 , ABCC10 , GTF2H2 , XPA , XPC and XRCC1 ) were associated with cisplatin chemoresistance and could therefore contribute to the development of a predictive marker. Standardized RT (StaRT)-PCR, was employed to assess these genes in a set of NSCLC cell lines with a previously published range of sensitivity to cisplatin. Data were obtained in the form of target gene molecules relative to 10^6 β-actin ( ACTB ) molecules. To cancel the effect of ACTB variation among the different cell lines individual gene expression values were incorporated into ratios of one gene to another. Each two-gene ratio was compared as a single variable to chemoresistance for each of eight NSCLC cell lines using multiple regression. In an effort to validate these results, six additional lines then were evaluated. Results Following validation, single variable models best correlated with chemoresistance (p < 0.001), were ERCC2/XPC , ABCC5/GTF2H2 , ERCC2/GTF2H2 , XPA/XPC and XRCC1/XPC . All single variable models were examined hierarchically to achieve two variable models. The two variable model with the highest correlation was ( ABCC5/GTF2H2 , ERCC2/GTF2H2 ) with an R^2 value of 0.96 (p < 0.001). Conclusion These results provide markers suitable for assessment of small fine needle aspirate biopsies in an effort to prospectively identify cisplatin resistant tumors.

Sadik A. Khuder - One of the best experts on this subject based on the ideXlab platform.

  • ABCC5 ercc2 xpa and xrcc1 transcript abundance levels correlate with cisplatin chemoresistance in non small cell lung cancer cell lines
    Molecular Cancer, 2005
    Co-Authors: David A Weaver, Kristy A Warner, Fadel Elkhairi, Erin L. Crawford, Sadik A. Khuder, James C Willey
    Abstract:

    Background Although 40–50% of non-small cell lung cancer (NSCLC) tumors respond to cisplatin chemotherapy, there currently is no way to prospectively identify potential responders. The purpose of this study was to determine whether transcript abundance (TA) levels of twelve selected DNA repair or multi-drug resistance genes (LIG1, ERCC2, ERCC3, DDIT3, ABCC1, ABCC4, ABCC5, ABCC10, GTF2H2, XPA, XPC and XRCC1) were associated with cisplatin chemoresistance and could therefore contribute to the development of a predictive marker. Standardized RT (StaRT)-PCR, was employed to assess these genes in a set of NSCLC cell lines with a previously published range of sensitivity to cisplatin. Data were obtained in the form of target gene molecules relative to 106 β-actin (ACTB) molecules. To cancel the effect of ACTB variation among the different cell lines individual gene expression values were incorporated into ratios of one gene to another. Each two-gene ratio was compared as a single variable to chemoresistance for each of eight NSCLC cell lines using multiple regression. In an effort to validate these results, six additional lines then were evaluated.

  • ABCC5, ERCC2, XPA and XRCC1 transcript abundance levels correlate with cisplatin chemoresistance in non-small cell lung cancer cell lines
    Molecular Cancer, 2005
    Co-Authors: David A Weaver, Kristy A Warner, Fadel Elkhairi, Erin L. Crawford, Sadik A. Khuder, James C Willey
    Abstract:

    Background Although 40–50% of non-small cell lung cancer (NSCLC) tumors respond to cisplatin chemotherapy, there currently is no way to prospectively identify potential responders. The purpose of this study was to determine whether transcript abundance (TA) levels of twelve selected DNA repair or multi-drug resistance genes ( LIG1 , ERCC2 , ERCC3 , DDIT3 , ABCC1 , ABCC4 , ABCC5 , ABCC10 , GTF2H2 , XPA , XPC and XRCC1 ) were associated with cisplatin chemoresistance and could therefore contribute to the development of a predictive marker. Standardized RT (StaRT)-PCR, was employed to assess these genes in a set of NSCLC cell lines with a previously published range of sensitivity to cisplatin. Data were obtained in the form of target gene molecules relative to 10^6 β-actin ( ACTB ) molecules. To cancel the effect of ACTB variation among the different cell lines individual gene expression values were incorporated into ratios of one gene to another. Each two-gene ratio was compared as a single variable to chemoresistance for each of eight NSCLC cell lines using multiple regression. In an effort to validate these results, six additional lines then were evaluated. Results Following validation, single variable models best correlated with chemoresistance (p < 0.001), were ERCC2/XPC , ABCC5/GTF2H2 , ERCC2/GTF2H2 , XPA/XPC and XRCC1/XPC . All single variable models were examined hierarchically to achieve two variable models. The two variable model with the highest correlation was ( ABCC5/GTF2H2 , ERCC2/GTF2H2 ) with an R^2 value of 0.96 (p < 0.001). Conclusion These results provide markers suitable for assessment of small fine needle aspirate biopsies in an effort to prospectively identify cisplatin resistant tumors.