Tumour Necrosis Factor Alpha and Oxidative Stress in the Breath Condensate of Those with Non-Small Cell Lung Cancer


Background and Aims: Lung cancer is a leading cause of cancer mortality worldwide and is associated with the release of tumour necrosis factor-α (TNF-α), subsequent cellular apoptosis and the generation of oxidative stress. Exhaled breath condensate (EBC) analysis is a non-invasive method for sampling biofluids from the lower respiratory tract. This study aimed to evaluate possible biomarkers of lung cancer by measuring the levels of TNF-α and the oxidation of ascorbic acid in EBC. Patients with lung cancer were enrolled into the study prior to treatment, during treatment and post-treatment, and results compared with an age-matched control population. Material and Methods: Patients with Stage II-IV non small cell lung cancer (NSCLC) were recruited prior to and at stages of their treatment. EBC levels of TNF-α, and rate of ascorbic acid oxidation were measured. Results: A total of 19 patients with NSCLC (mean age 71.37 ± 7.77 yrs) and 25 age-matched control subjects were enrolled. Levels of EBC TNF-α were elevated in the EBC of patients with lung cancer compared with control subjects (1.02 ± 0.07 pg/ml vs. 0.51 ± 0.06 pg/ml, p < 0.0001). Moreover, the rate of ascorbic acid oxidation was significantly greater in the EBC of patients with lung cancer compared with control subjects (2.20% [0.4 – 11.0] vs. 1.00% [0.1 – 8.5], p = 0.0244). Conclusion: TNF-α and the rate of ascorbic acid oxidation was elevated in the EBC of patients with lung cancer regardless of treatment. Longitudinal studies in a larger population are required to evaluate these markers for the effect of treatment and prognosis.

Share and Cite:

E. Chan, T. Sivagnanam, Q. Zhang, C. Lewis and P. Thomas, "Tumour Necrosis Factor Alpha and Oxidative Stress in the Breath Condensate of Those with Non-Small Cell Lung Cancer," Journal of Cancer Therapy, Vol. 3 No. 4A, 2012, pp. 460-466. doi: 10.4236/jct.2012.324059.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] J. Ferlay, H.-R. Shin, F. Bray, et al., “Parkin. Estimates of Worldwide Burden of Cancer in 2008: GLOBOCAN 2008,” International Journal of Cancer, Vol. 127, No. 12, 2010, pp. 2893-2917. doi:10.1002/ijc.25516
[2] C. D. Mathers and D. Loncar, “Projections of Global Mortalitly and Burden of Disease from 2002 and 2030,” PLoS Medicine, Vol. 3, 2006, p. 3442. doi:10.1371/journal.pmed.0030442
[3] A. Hemal, R. Siegel, E. Ward, et al., “Cancer Statistics 2008,” CA—A Cancer Journal for Clinicians, Vol. 58, No. 2, 2008, pp. 71-96. doi:10.3322/CA.2007.0010
[4] (AIHW) AIoHaW, “ACIM (Australian Cancer Incidence and Mortality),” AIHW, Canberra, 2010.
[5] U. Ahmad, M. Ruschel and F. C. Detterbeck, “Lung Cancer: Facts, Figures and Reflections on Spending,” Journal of Cancer Therapy, Vol. 3, No. 2, 2012, pp. 123-126. doi:10.4236/jct.2012.32016
[6] C. Mountain, “Revisions in the International System for Staging Lung Cancer,” Chest, Vol. 111, No. 6, 1997, pp. 1710-1717. doi:10.1378/chest.111.6.1710
[7] W. De Weaver, S. Stroobants, J. Coden, et al., “Integrated PET/CT in the Staging of Non Small Cell Lung Cancer: Technical Aspects and Resection for Lung Cancer,” European Respiratory Journal, Vol. 33, 2009, pp. 201-212. doi:10.1183/09031936.00035108
[8] A. McWilliams, B. Lam and T. Sutedja, “Early Proximal Lung Cancer Diagnosis and Treatment,” European Respiratory Journal, Vol. 33, 2009, pp. 656-665. doi:10.1183/09031936.00124608
[9] P. B. Bach, D. E. Niewoehner and W. C. Black, “Screening for Lung Cancer: The Guidleines,” Chest, Vol. 123, No. 1, 2003, pp. 83S-88S. doi:10.1378/chest.123.1_suppl.83S
[10] E. Edell, S. Lam, H. Pass, et al., “Detection and Localisation of Intraepithelial Neoplasia and Invasive Carcinoma Using Fluorescence-Reflectance Bronschospcopy: An International, Multicenter Clinical Trial,” Journal of Thoracic Oncology, Vol. 4, 2009, pp. 49-54.
[11] H. P. Chan, V. Tran, C. Lewis and P. S. Thomas, “Elevated Levels of Oxidative Stress Markers in Exhaled Breath Condensate,” Journal of Thoracic Oncology, Vol. 4, No. 2, 2009, pp. 172-178. doi:10.1097/JTO.0b013e3181949eb9
[12] H. P. Chan, C. Lewis and P. S. Thomas, “Exhaled Breath Analysis: Novel Approach for Early Detection of Lung Cancer,” Lung Cancer, Vol. 63, No. 2, 2009, pp. 164-168. doi:10.1016/j.lungcan.2008.05.020
[13] D. H. Conrad, J. Goyette and P. S. Thomas, “Proteomics as a Method for Early Detection of Cancer: A Review of Proteomics, Exhaled Breath Condensate, and Lung Cancer Screening,” Journal of General Internal Medicine, Vol. 23, No. 1S, 2007, pp. 78-84.
[14] K. L. Reckamp, B. K. Gardner, R. A. Figlin, et al., “Tumor Response to Combination Celecoxib and Erlotinib Therapy in Non-Small Cell Lung Cancer Is Associated with a Low Baseline Matrix Metalloproteinase-9 and a Decline in Serum-Soluble E-Cadherin,” Journal of Thoracic Oncology, Vol. 3, No. 2, 2008, pp. 117-124. doi:10.1097/JTO.0b013e3181622bef
[15] D. Derin, H. O. Soydinc, N. Guney, et al., “ Serum Levels of Apoptosis Biomarkers and TNF-Alpha in Nonsmall Cell Lung Cancer,” Lung Cancer, Vol. 59, No. 2, 2008, pp. 240-245. doi:10.1016/j.lungcan.2007.08.005
[16] E. Dalaveris, T. Kerenidi, A. Katsabeki-Katsafli, et al., “VEGF, TNF-Alpha and 8-Isoprostane Levels in Exhaled Breath Condensate and Serum of Patients with Lung Cancer,” Lung Cancer, Vol. 64, No. 2, 2009, pp. 219-225. doi:10.1016/j.lungcan.2008.08.015
[17] P. W. Szlosarek and F. R. Balkwill, “Tumour Necrosis Factor α: A Potential Target for the Therapy of Solid Tumors,” The Lancet Oncology, Vol. 4, No. 1, 2003, pp. 565-573. doi:10.1016/S1470-2045(03)01196-3
[18] P. Montuschi and P. J. Barnes, “Analysis of Exhaled Breath Condensate for Monitoring Airway Inflammation,” Trends in Pharmacological Sciences, Vol. 23, No. 5, 2002, pp. 232-237. doi:10.1016/S0165-6147(02)02020-5
[19] K. Garey, M. M. Neuhauser, R. A. Robbins, L. H. Danziger and I. Rubinstein, “Markers of Inflammation in Exhaled Breath Condensate of Young Healthy Smokers,” Chest, Vol. 125, No. 1, 2004, pp. 22-26. doi:10.1378/chest.125.1.22
[20] D. Nowak, S. Kalucka, P. Bia?asiewicz and M. Król, “Exhalation of H2O2 and Thiobarbituric Acid Reactive Substances (TBARs) by Healthy Subjects,” Free Radical Biology & Medicine, Vol. 30, No. 2, 2001, pp. 178-186. doi:10.1016/S0891-5849(00)00457-3
[21] S. Doruk, H. Ozyurt, H. Inonu, U. Erkorkmaz, O. Saylan and Z. Seyfikli, “Oxidative Status in the Lungs Associated with Tobacco Smoke Exposure,” Clinical Chemistry and Laboratory Medicine, 2011, in Press. doi:10.1515/CCLM.2011.698
[22] H. P. Chan, C. R. Lewis and P. S. Thomas, “Oxidative Stress and Exhaled Breath Analysis: A Promising Tool for Detection of Lung Cancer,” Cancers, Vol. 2, No. 1, 2010, pp. 32-42. doi:10.3390/cancers2010032
[23] T. P. Szatrowski and C. F. Nathan, “Production of Large Amounts of Hydrogen Peroxide by Human Tumor Cells,” Cancer Research, Vol. 51, No. 3, 1991, pp. 794-798.
[24] M. D. Evans, M. Dizdaroglu and M. S. Cooke, “Oxidative DNA Damage and Disease: Induction, Repair and Significance,” Mutation Research, Vol. 567, No. 1, 2004, pp. 1-61. doi:10.1016/j.mrrev.2003.11.001
[25] O. Vafa, M. Wade, S. Kern, et al., “c-Myc Can Induce DNA Damage, Increased Reactive Oxygen Species, and Mitigate p53 Function: A Mechanism for Oncogene-Induced Genetic Instability,” Molecular Cell, Vol. 9 No. 5, 2002, pp. 1031-1044. doi:10.1016/S1097-2765(02)00520-8
[26] L. Hlavata, H. Aguilaniu, A. Pichova, et al., “The Oncogenic RAS2val19 Mutation Locks Respiration, Independently of PKA, in a Mode Prone to Generate ROS,” European Molecular Biology Organization Journal, Vol. 22, No. 13, 2003, pp. 3337-3345. doi:10.1093/emboj/cdg314
[27] H. Pelicano, D. Carney and P. Huang, “ROS Stress in Cancer Cells and Therapeutic Implications,” Drug Resistance Updates, Vol. 7, No. 1, 2004, pp. 97-110. doi:10.1016/j.drup.2004.01.004
[28] D. R. Spitz, E. L. Azzam, J. J. Li and D. Gius, “Metabolic Oxidation/Reduction Reactions and Cellular Responses to Ionizing Radiation: A Unifying Concepts in Stress Response Biology,” Cancer and Metastasis Reviews, Vol. 23, No. 1, 2004, pp. 311-322. doi:10.1023/B:CANC.0000031769.14728.bc
[29] J. E. Bigalow, J. B. Mitchell and K. Held, “The Importance of Peroxide and superoxide in the Xray Response,” Internal Journal of radiation Oncology, Biology, Physics, Vol. 22, No. 1, 1992, pp. 665-669.
[30] G. R. Buettner, “Ascorbate Oxidation: UV Absorbance of Ascorbate and ESR Spectroscopy of the Ascorbyl Radical as Assay for Iron,” Informa Healthcare, Vol. 10, No. 1-2, 1990, pp. 5-9.
[31] L. Boldrini, A. Calcinai, E. Samaritani, et al., “Tumour Necrosis Factor-Alpha and Transforming Growth Factor-Beta Are Significantly Associated with Better Prognosis in Non-Small Cell Lung Carcinoma: Putative Relation with BCL-2-Mediated Neovascularization,” British Journal of Cancer, Vol. 83, No. 1, 2000, pp. 480-486. doi:10.1054/bjoc.2000.1345
[32] L. Gibellini, M. Pinti, M. Nasi, et al., “Interfering with ROS Metabolism in Cancer Cells: The Potential Role of Quercetin,” Cancer, Vol. 2, No. 1, 2010, pp. 1288-1311.
[33] Z. Cheng, C. R. Lewis, P. S. Thomas, et al., “Comparative Proteomics Analysis of Exhaled Breath Condensate in Lung Cancer Patients,” Journal of Cancer Therapy, Vol. 2, No. 1, 2011, pp. 1-8. doi:10.4236/jct.2011.21001
[34] I. Horvath, J. Hunt and P. J. Barnes, “Exhaled Breath Condensate: Methodological Recommendations and Unresolved Questions,” European Respiratory Journal, Vol. 26, No. 3, 2005, pp. 523-548. doi:10.1183/09031936.05.00029705
[35] F. Imer, E. Aldemir, H. Kilic, et al., “The Protective Effect of Amino Acids on the Copper(II)-Catalyzed Autoxidation of Ascorbic Acid,” Journal of Food and Drug Analysis, Vol. 16, No. 6, 2008, pp. 46-53.
[36] M. N. Khan and A. Sarwar, “The Influence of Transition Metal Ions on the Kinetics of Ascorbic Acid Oxidation by Methylene Blue in Strongly Acidic Media,” Turkish Journal of Chemistry, Vol. 25, No. 1, 2001, pp. 433-440.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.