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Individual responses to chemotherapy-induced oxidative stress

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Abstract

Differences in redox homeostatic control between cancer patients may underlie predisposition to drug resistance and toxicities. To evaluate interindividual differences in redox response among newly diagnosed breast cancer patients undergoing standard chemotherapy, urine samples were collected before (T0), and at 1 (T1) and 24 h (T24) after chemotherapy administration. Oxidative status was assessed by urinary levels of allantoin and four F2-isoprostanes, quantified by LC–MS/MS. In all subjects, biomarker levels increased at T1 and returned to baseline at T24. Analyzing individual responses, two patterns were revealed: 10 subjects showed uniform increases of biomarker levels at T1 (“increase” pattern) and 8 subjects showed mixed (increase/unchanged/decrease) responses for different biomarkers (“mixed” pattern). The increase-pattern group had lower pre-treatment (T0) levels of the biomarkers and showed a sharp increase at T1 (64–141%) with a subsequent decrease at T24. The mixed-pattern group had higher pre-treatment biomarker levels and showed no change in biomarkers either at T1 or at T24. These findings indicate that there may be at least two distinct redox phenotypes with different homeostatic mechanisms balancing oxidative stress in humans. Recognizing redox phenotypes in human populations may lead to more precise assessment of health risks and benefits associated with individual redox make-up, and may also help to identify cancer patients who are especially susceptible to drug resistance and/or drug toxicity.

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Fig. 1

Abbreviations

AMPK:

AMP-activated protein kinase

LC–MS/MS:

liquid chromatography-tandem mass spectrometry

PGC-1-α:

peroxisome proliferator-activated receptor-γ coactivator-1α

T0:

time point of urine collection before administration of doxorubicin

T1:

time point of urine collection 1 h after administration of doxorubicin

T24:

time point of urine collection 24 h after administration of doxorubicin

UCPs:

uncoupling proteins (1-6)

UPLC–MS/MS:

ultra performance liquid chromatography-tandem mass spectrometry

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Acknowledgments

This research was funded by a Duke Comprehensive Cancer Center pilot study award, NIH SPORE Grant 5P50 CA68438, the Department of Defense Breast Cancer Research Program (BCRP) predoctoral traineeship award BC083154, and Anna Merills’ Fund for Down Syndrome Research Foundation grant.

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Authors and Affiliations

  1. Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, NC, 27710, USA

    Dora Il’yasova, Ivan Spasojevic, Frances Wang, Karel Base, P. Kelly Marcom & Jeffrey Marks

  2. Department of Pathology, Duke University Medical Center, Durham, NC, USA

    Kelly Kennedy

  3. Department of Pediatrics, Medical Genetics Division, Duke University Medical Center, Durham, NC, USA

    Adviye A. Tolun, Sarah P. Young & David S. Millington

  4. Radiation Oncology Department and Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, NC, USA

    Mark W. Dewhirst

Authors
  1. Dora Il’yasova
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  2. Kelly Kennedy
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Correspondence to Dora Il’yasova.

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Authors of this manuscript, Dora Il’yasova, Kelly Kennedy, Ivan Spasojevic, Frances Wang, Adviye A. Tolun, Karel Base, Sarah P. Young, P Kelly Marcom, Jeffrey Marks, David S. Millington, and Mark Dewhirst, have neither actual nor potential commercial associations that might create a conflict of interest in connection with submitted manuscripts.

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Il’yasova, D., Kennedy, K., Spasojevic, I. et al. Individual responses to chemotherapy-induced oxidative stress. Breast Cancer Res Treat 125, 583–589 (2011). https://doi.org/10.1007/s10549-010-1158-7

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