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Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer

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Abstract

Breast cancer is the malignant neoplasia with the highest incidence in women worldwide. Chronic oxidative stress and inflammation have been indicated as major mediators during carcinogenesis and cancer progression. Human studies have not considered the complexity of tumor biology during the stages of cancer advance, limiting their clinical application. The purpose of this study was to characterize systemic oxidative stress and immune response parameters in early (ED; TNM I and II) and advanced disease (AD; TNM III and IV) of patients diagnosed with infiltrative ductal carcinoma breast cancer. Oxidative stress parameters were evaluated by plasmatic lipoperoxidation, carbonyl content, thiobarbituric reactive substances (TBARS), nitric oxide levels (NO), total radical antioxidant parameter (TRAP), superoxide dismutase, and catalase activities and GSH levels. Immune evaluation was determined by TNF-α, IL-1β, IL-12, and IL-10 levels and leukocytes oxidative burst evaluation by chemiluminescence. Tissue damage analysis included heart (total CK and CKMB), liver (AST, ALT, GGT), and renal (creatinine, urea, and uric acid) plasmatic markers. C-reactive protein (CRP) and iron metabolism were also evaluated. Analysis of the results verified different oxidative stress statuses occur at distinct cancer stages. ED was characterized by reduction in catalase, 8-isoprostanes, and GSH levels, with enhanced lipid peroxidation and TBARS levels. AD exhibited more pronounced oxidative status, with reduction in catalase activity and TRAP, intense lipid peroxidation and high levels of NO, TBARs, and carbonyl content. ED patients presented a Th2 immune pattern, while AD exhibited Th1 status. CRP levels and ferritin were increased in both stages of disease. Leukocytes burst impairment was observed in both the groups. Plasma iron levels were significantly elevated in AD. The data obtained indicated that oxidative stress enhancement and immune response impairment may be necessary to ensure cancer progression to advanced stages and may result from both host and tumor inflammatory mediators.

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Abbreviations

AD:

Advanced breast cancer patients

ED:

Early disease breast cancer patients

TNM:

Tumor node metastasis classification

SOD:

Superoxide dismutase

GSH:

Reduced glutathione

TCA:

Trichloric acetic acid

TRAP:

Total antioxidant capacity

ABAP:

2,2′azobis

RLU:

Relative light unities

NO:

Nitric oxide

TBARS:

Thiobarbituric reactive substances

MDA:

Malondialdehyde

DNPH:

Dinitrophenylhydrazine

AUC:

Area under the curve

LDL:

Low density lipoprotein

CL:

Chemiluminescence

TNF-α:

Tumor necrosis factor alpha

ER:

Estrogen receptors

PR:

Progesterone receptors

HER-2:

Human epidermal growth factor receptor

CAT:

Catalase

GSH:

Reduced glutathione

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

GGT:

Gamma glutamyl transpeptidase

CK:

Creatine kinase

CKMB:

Creatine kinase MB fraction

URCA:

Uric acid levels

IL-1:

Interleukin 1

IL-6:

Interleukin 6

IL-12:

Interleukin 12

IL-10:

Interleukin 10

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Acknowledgments

The authors are grateful to Jesus Vargas for his exceptional technical assistance and the Fundação Araucária, CNPq and CAPES for providing financial support.

Conflict of interest

The authors declare there are no conflicts of interest.

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Authors and Affiliations

  1. Laboratório de Patologia e Radicais Livres, Departamento de Patologia Geral—Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, 86051-990, Brazil

    C. Panis, V. J. Victorino, A. C. S. A. Herrera, L. F. Freitas, T. De Rossi, F. C. Campos, R. Cecchini & A. L. Cecchini

  2. Hospital Universitario, Departamento de Farmacia, Universidade Estadual de Londrina, Londrina, Paraná, Brazil

    A. N. Colado Simão & D. S. Barbosa

  3. Laboratório de Imunopatologia, Departamento de Patologia Geral—Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil

    P. Pinge-Filho

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  1. C. Panis
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  2. V. J. Victorino
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  3. A. C. S. A. Herrera
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  10. R. Cecchini
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Correspondence to A. L. Cecchini.

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Panis, C., Victorino, V.J., Herrera, A.C.S.A. et al. Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer. Breast Cancer Res Treat 133, 881–888 (2012). https://doi.org/10.1007/s10549-011-1851-1

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