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Ignacio I Wistuba - One of the best experts on this subject based on the ideXlab platform.

  • copper transporter ctr1 expression and tissue Platinum concentration in non small cell lung cancer
    Lung Cancer, 2014
    Co-Authors: Ximing Tang, Chi Wan Chow, Junya Fujimoto, Neda Kalhor, Stephen G Swisher, David J Stewart, Derick R Peterson, Deepak Kilari, Ignacio I Wistuba
    Abstract:

    Abstract Background Platinum resistance is a major limitation in the treatment of advanced non-small cell lung cancer (NSCLC). We previously demonstrated that low tissue Platinum concentration in NSCLC specimens was significantly associated with reduced tumor response. Furthermore, low expression of the copper transporter CTR1, a transporter of Platinum uptake was associated with poor clinical outcome following Platinum-based therapy in NSCLC patients. We investigated the relationship between tissue Platinum concentrations and CTR1 expression in NSCLC specimens. Methods We identified paraffin-embedded NSCLC tissue blocks of known tissue Platinum concentrations from 30 patients who underwent neoadjuvant Platinum-based chemotherapy at MD Anderson Cancer Center. Expression of CTR1 in tumors and normal adjacent lung specimens was determined by immunohistochemistry with adequate controls. Results Tissue Platinum concentration significantly correlated with tumor response in 30 patients who received neoadjuvant Platinum-based chemotherapy ( P P =0.058) and tumor response ( P =0.016) compared to those with any level of CTR1 expression. We also observed that African Americans had significantly reduced CTR1 expression scores ( P =0.001), tissue Platinum concentrations ( P =0.009) and tumor shrinkage ( P =0.016) compared to Caucasians. Conclusions To our best knowledge this is the first study investigating the function of CTR1 in clinical specimens. CTR1 expression may be necessary for therapeutic efficacy of Platinum drugs, consistent with previous preclinical studies. A prospective clinical trial is necessary to develop CTR1 into a potential biomarker for Platinum drugs.

  • tissue Platinum concentration and tumor response in non small cell lung cancer
    Journal of Clinical Oncology, 2012
    Co-Authors: Guangan He, Chi Wan Chow, Junya Fujimoto, Neda Kalhor, Stephen G Swisher, Ignacio I Wistuba, David J Stewart, Zahid H Siddik
    Abstract:

    Purpose Platinum resistance is a major limitation in the treatment of advanced non–small-cell lung cancer (NSCLC). Reduced intracellular drug accumulation is one of the most consistently identified features of Platinum-resistant cell lines, but clinical data are limited. We assessed the effects of tissue Platinum concentrations on response and survival in NSCLC. Patients and Methods We measured total Platinum concentrations by flameless atomic absorption spectrophotometry in 44 archived fresh-frozen NSCLC specimens from patients who underwent surgical resection after neoadjuvant Platinum-based chemotherapy. Tissue Platinum concentration was correlated with percent reduction in tumor size on post- versus prechemotherapy computed tomography scans. The relationship between tissue Platinum concentration and survival was assessed by univariate and multicovariate Cox proportional hazards regression model analysis and Kaplan-Meier analysis. Results Tissue Platinum concentration correlated significantly with percent reduction in tumor size (P .001). The same correlations were seen with cisplatin, carboplatin, and all histology subgroups. Furthermore, there was no significant impact of potential variables such as number of cycles and time lapse from last chemotherapy on Platinum concentration. Patients with higher Platinum concentration had longer time to recurrence (P .034), progression-free survival (P .018), and overall survival (P .005) in the multicovariate Cox model analysis after adjusting for number of cycles. Conclusion This clinical study established a relationship between tissue Platinum concentration and response in NSCLC. It suggests that reduced Platinum accumulation might be an important mechanism of Platinum resistance in the clinical setting. Further studies investigating factors that modulate intracellular Platinum concentration are warranted.

David J Stewart - One of the best experts on this subject based on the ideXlab platform.

  • copper transporter ctr1 expression and tissue Platinum concentration in non small cell lung cancer
    Lung Cancer, 2014
    Co-Authors: Ximing Tang, Chi Wan Chow, Junya Fujimoto, Neda Kalhor, Stephen G Swisher, David J Stewart, Derick R Peterson, Deepak Kilari, Ignacio I Wistuba
    Abstract:

    Abstract Background Platinum resistance is a major limitation in the treatment of advanced non-small cell lung cancer (NSCLC). We previously demonstrated that low tissue Platinum concentration in NSCLC specimens was significantly associated with reduced tumor response. Furthermore, low expression of the copper transporter CTR1, a transporter of Platinum uptake was associated with poor clinical outcome following Platinum-based therapy in NSCLC patients. We investigated the relationship between tissue Platinum concentrations and CTR1 expression in NSCLC specimens. Methods We identified paraffin-embedded NSCLC tissue blocks of known tissue Platinum concentrations from 30 patients who underwent neoadjuvant Platinum-based chemotherapy at MD Anderson Cancer Center. Expression of CTR1 in tumors and normal adjacent lung specimens was determined by immunohistochemistry with adequate controls. Results Tissue Platinum concentration significantly correlated with tumor response in 30 patients who received neoadjuvant Platinum-based chemotherapy ( P P =0.058) and tumor response ( P =0.016) compared to those with any level of CTR1 expression. We also observed that African Americans had significantly reduced CTR1 expression scores ( P =0.001), tissue Platinum concentrations ( P =0.009) and tumor shrinkage ( P =0.016) compared to Caucasians. Conclusions To our best knowledge this is the first study investigating the function of CTR1 in clinical specimens. CTR1 expression may be necessary for therapeutic efficacy of Platinum drugs, consistent with previous preclinical studies. A prospective clinical trial is necessary to develop CTR1 into a potential biomarker for Platinum drugs.

  • tissue Platinum concentration and tumor response in non small cell lung cancer
    Journal of Clinical Oncology, 2012
    Co-Authors: Guangan He, Chi Wan Chow, Junya Fujimoto, Neda Kalhor, Stephen G Swisher, Ignacio I Wistuba, David J Stewart, Zahid H Siddik
    Abstract:

    Purpose Platinum resistance is a major limitation in the treatment of advanced non–small-cell lung cancer (NSCLC). Reduced intracellular drug accumulation is one of the most consistently identified features of Platinum-resistant cell lines, but clinical data are limited. We assessed the effects of tissue Platinum concentrations on response and survival in NSCLC. Patients and Methods We measured total Platinum concentrations by flameless atomic absorption spectrophotometry in 44 archived fresh-frozen NSCLC specimens from patients who underwent surgical resection after neoadjuvant Platinum-based chemotherapy. Tissue Platinum concentration was correlated with percent reduction in tumor size on post- versus prechemotherapy computed tomography scans. The relationship between tissue Platinum concentration and survival was assessed by univariate and multicovariate Cox proportional hazards regression model analysis and Kaplan-Meier analysis. Results Tissue Platinum concentration correlated significantly with percent reduction in tumor size (P .001). The same correlations were seen with cisplatin, carboplatin, and all histology subgroups. Furthermore, there was no significant impact of potential variables such as number of cycles and time lapse from last chemotherapy on Platinum concentration. Patients with higher Platinum concentration had longer time to recurrence (P .034), progression-free survival (P .018), and overall survival (P .005) in the multicovariate Cox model analysis after adjusting for number of cycles. Conclusion This clinical study established a relationship between tissue Platinum concentration and response in NSCLC. It suggests that reduced Platinum accumulation might be an important mechanism of Platinum resistance in the clinical setting. Further studies investigating factors that modulate intracellular Platinum concentration are warranted.

Zahid H Siddik - One of the best experts on this subject based on the ideXlab platform.

  • tissue Platinum concentration and tumor response in non small cell lung cancer
    Journal of Clinical Oncology, 2012
    Co-Authors: Guangan He, Chi Wan Chow, Junya Fujimoto, Neda Kalhor, Stephen G Swisher, Ignacio I Wistuba, David J Stewart, Zahid H Siddik
    Abstract:

    Purpose Platinum resistance is a major limitation in the treatment of advanced non–small-cell lung cancer (NSCLC). Reduced intracellular drug accumulation is one of the most consistently identified features of Platinum-resistant cell lines, but clinical data are limited. We assessed the effects of tissue Platinum concentrations on response and survival in NSCLC. Patients and Methods We measured total Platinum concentrations by flameless atomic absorption spectrophotometry in 44 archived fresh-frozen NSCLC specimens from patients who underwent surgical resection after neoadjuvant Platinum-based chemotherapy. Tissue Platinum concentration was correlated with percent reduction in tumor size on post- versus prechemotherapy computed tomography scans. The relationship between tissue Platinum concentration and survival was assessed by univariate and multicovariate Cox proportional hazards regression model analysis and Kaplan-Meier analysis. Results Tissue Platinum concentration correlated significantly with percent reduction in tumor size (P .001). The same correlations were seen with cisplatin, carboplatin, and all histology subgroups. Furthermore, there was no significant impact of potential variables such as number of cycles and time lapse from last chemotherapy on Platinum concentration. Patients with higher Platinum concentration had longer time to recurrence (P .034), progression-free survival (P .018), and overall survival (P .005) in the multicovariate Cox model analysis after adjusting for number of cycles. Conclusion This clinical study established a relationship between tissue Platinum concentration and response in NSCLC. It suggests that reduced Platinum accumulation might be an important mechanism of Platinum resistance in the clinical setting. Further studies investigating factors that modulate intracellular Platinum concentration are warranted.

Chi Wan Chow - One of the best experts on this subject based on the ideXlab platform.

  • copper transporter ctr1 expression and tissue Platinum concentration in non small cell lung cancer
    Lung Cancer, 2014
    Co-Authors: Ximing Tang, Chi Wan Chow, Junya Fujimoto, Neda Kalhor, Stephen G Swisher, David J Stewart, Derick R Peterson, Deepak Kilari, Ignacio I Wistuba
    Abstract:

    Abstract Background Platinum resistance is a major limitation in the treatment of advanced non-small cell lung cancer (NSCLC). We previously demonstrated that low tissue Platinum concentration in NSCLC specimens was significantly associated with reduced tumor response. Furthermore, low expression of the copper transporter CTR1, a transporter of Platinum uptake was associated with poor clinical outcome following Platinum-based therapy in NSCLC patients. We investigated the relationship between tissue Platinum concentrations and CTR1 expression in NSCLC specimens. Methods We identified paraffin-embedded NSCLC tissue blocks of known tissue Platinum concentrations from 30 patients who underwent neoadjuvant Platinum-based chemotherapy at MD Anderson Cancer Center. Expression of CTR1 in tumors and normal adjacent lung specimens was determined by immunohistochemistry with adequate controls. Results Tissue Platinum concentration significantly correlated with tumor response in 30 patients who received neoadjuvant Platinum-based chemotherapy ( P P =0.058) and tumor response ( P =0.016) compared to those with any level of CTR1 expression. We also observed that African Americans had significantly reduced CTR1 expression scores ( P =0.001), tissue Platinum concentrations ( P =0.009) and tumor shrinkage ( P =0.016) compared to Caucasians. Conclusions To our best knowledge this is the first study investigating the function of CTR1 in clinical specimens. CTR1 expression may be necessary for therapeutic efficacy of Platinum drugs, consistent with previous preclinical studies. A prospective clinical trial is necessary to develop CTR1 into a potential biomarker for Platinum drugs.

  • tissue Platinum concentration and tumor response in non small cell lung cancer
    Journal of Clinical Oncology, 2012
    Co-Authors: Guangan He, Chi Wan Chow, Junya Fujimoto, Neda Kalhor, Stephen G Swisher, Ignacio I Wistuba, David J Stewart, Zahid H Siddik
    Abstract:

    Purpose Platinum resistance is a major limitation in the treatment of advanced non–small-cell lung cancer (NSCLC). Reduced intracellular drug accumulation is one of the most consistently identified features of Platinum-resistant cell lines, but clinical data are limited. We assessed the effects of tissue Platinum concentrations on response and survival in NSCLC. Patients and Methods We measured total Platinum concentrations by flameless atomic absorption spectrophotometry in 44 archived fresh-frozen NSCLC specimens from patients who underwent surgical resection after neoadjuvant Platinum-based chemotherapy. Tissue Platinum concentration was correlated with percent reduction in tumor size on post- versus prechemotherapy computed tomography scans. The relationship between tissue Platinum concentration and survival was assessed by univariate and multicovariate Cox proportional hazards regression model analysis and Kaplan-Meier analysis. Results Tissue Platinum concentration correlated significantly with percent reduction in tumor size (P .001). The same correlations were seen with cisplatin, carboplatin, and all histology subgroups. Furthermore, there was no significant impact of potential variables such as number of cycles and time lapse from last chemotherapy on Platinum concentration. Patients with higher Platinum concentration had longer time to recurrence (P .034), progression-free survival (P .018), and overall survival (P .005) in the multicovariate Cox model analysis after adjusting for number of cycles. Conclusion This clinical study established a relationship between tissue Platinum concentration and response in NSCLC. It suggests that reduced Platinum accumulation might be an important mechanism of Platinum resistance in the clinical setting. Further studies investigating factors that modulate intracellular Platinum concentration are warranted.

Junya Fujimoto - One of the best experts on this subject based on the ideXlab platform.

  • copper transporter ctr1 expression and tissue Platinum concentration in non small cell lung cancer
    Lung Cancer, 2014
    Co-Authors: Ximing Tang, Chi Wan Chow, Junya Fujimoto, Neda Kalhor, Stephen G Swisher, David J Stewart, Derick R Peterson, Deepak Kilari, Ignacio I Wistuba
    Abstract:

    Abstract Background Platinum resistance is a major limitation in the treatment of advanced non-small cell lung cancer (NSCLC). We previously demonstrated that low tissue Platinum concentration in NSCLC specimens was significantly associated with reduced tumor response. Furthermore, low expression of the copper transporter CTR1, a transporter of Platinum uptake was associated with poor clinical outcome following Platinum-based therapy in NSCLC patients. We investigated the relationship between tissue Platinum concentrations and CTR1 expression in NSCLC specimens. Methods We identified paraffin-embedded NSCLC tissue blocks of known tissue Platinum concentrations from 30 patients who underwent neoadjuvant Platinum-based chemotherapy at MD Anderson Cancer Center. Expression of CTR1 in tumors and normal adjacent lung specimens was determined by immunohistochemistry with adequate controls. Results Tissue Platinum concentration significantly correlated with tumor response in 30 patients who received neoadjuvant Platinum-based chemotherapy ( P P =0.058) and tumor response ( P =0.016) compared to those with any level of CTR1 expression. We also observed that African Americans had significantly reduced CTR1 expression scores ( P =0.001), tissue Platinum concentrations ( P =0.009) and tumor shrinkage ( P =0.016) compared to Caucasians. Conclusions To our best knowledge this is the first study investigating the function of CTR1 in clinical specimens. CTR1 expression may be necessary for therapeutic efficacy of Platinum drugs, consistent with previous preclinical studies. A prospective clinical trial is necessary to develop CTR1 into a potential biomarker for Platinum drugs.

  • tissue Platinum concentration and tumor response in non small cell lung cancer
    Journal of Clinical Oncology, 2012
    Co-Authors: Guangan He, Chi Wan Chow, Junya Fujimoto, Neda Kalhor, Stephen G Swisher, Ignacio I Wistuba, David J Stewart, Zahid H Siddik
    Abstract:

    Purpose Platinum resistance is a major limitation in the treatment of advanced non–small-cell lung cancer (NSCLC). Reduced intracellular drug accumulation is one of the most consistently identified features of Platinum-resistant cell lines, but clinical data are limited. We assessed the effects of tissue Platinum concentrations on response and survival in NSCLC. Patients and Methods We measured total Platinum concentrations by flameless atomic absorption spectrophotometry in 44 archived fresh-frozen NSCLC specimens from patients who underwent surgical resection after neoadjuvant Platinum-based chemotherapy. Tissue Platinum concentration was correlated with percent reduction in tumor size on post- versus prechemotherapy computed tomography scans. The relationship between tissue Platinum concentration and survival was assessed by univariate and multicovariate Cox proportional hazards regression model analysis and Kaplan-Meier analysis. Results Tissue Platinum concentration correlated significantly with percent reduction in tumor size (P .001). The same correlations were seen with cisplatin, carboplatin, and all histology subgroups. Furthermore, there was no significant impact of potential variables such as number of cycles and time lapse from last chemotherapy on Platinum concentration. Patients with higher Platinum concentration had longer time to recurrence (P .034), progression-free survival (P .018), and overall survival (P .005) in the multicovariate Cox model analysis after adjusting for number of cycles. Conclusion This clinical study established a relationship between tissue Platinum concentration and response in NSCLC. It suggests that reduced Platinum accumulation might be an important mechanism of Platinum resistance in the clinical setting. Further studies investigating factors that modulate intracellular Platinum concentration are warranted.