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Zaichick et al. J Cancer Metastasis Treat 2018;4:60  I  http://dx.doi.org/10.20517/2394-4722.2018.52                       Page 11 of 15

               Calcium phosphates are one of the main constituents of mineral deposits in aortic wall and tissues [117] . Thus,
               the high P level in TC can be intimately linked with tumor calcification [86-96] .


               S
               Proteins contain between 3% and 6% of sulfur amino acids. Sulfur amino acids contribute substantially
               to the maintenance and integrity of the cellular systems by influencing the cellular redox state and the
               capacity to detoxify toxic compounds, free radicals and ROS [118] . ROS are generated during normal cellular
               activity and may exist in excess in some pathophysiological conditions, such as inflammation. Therefore
               exploring fundamental aspects of sulfur metabolism such as the antioxidant effects of sulfur-containing
               amino acids [119]  may help elucidate the mechanism by which the S content increases in TC. Thus, it might
               be assumed that the elevated S level in cancerous thyroid reflects an increase in concentration of ROS in
               malignant tissue.

               Our findings show that mass fraction of Al, B, Br, Ca, Cl, Cu, I, K, Mg, Mn, Na, P, and S are significantly
               different in TC as compared to normal thyroid tissues [Table 6]. Thus, it is plausible to assume that levels
               of these chemical elements in thyroid tissue can be used as tumor markers. However, this subject needs in
               additional studies.

               Limitations
               This study has several limitations. Firstly, analytical techniques employed in this study measure only twenty
               element (Al, B, Ba, Br, Ca, Cl, Cu, Fe, I, K, Li, Mg, Mn, Na, P, S, Si, Sr, V, and Zn) mass fractions. Future
               studies should be directed toward using other analytical methods which will extend the list of chemical
               elements investigated in normal and cancerous thyroid tissue. Secondly, the sample size of TC group was
               relatively small. It does not allow us to carry out the investigations of chemical element contents in TC group
               using differentials like gender, histological types of tumors, stage of disease, and dietary habits of healthy
               persons and patients with TC. Lastly, the generalization of our results may be limited to Russian population.
               Despite these limitations, this study provides evidence on cancer-specific tissue Al, B, Br, Ca, Cl, Cu, I, K,
               Mg, Mn, Na, P, and S level alteration and shows the necessity to continue chemical element research of
               malignant thyroid tumors.


               DECLARATIONS
               Acknowledgments
               The authors are extremely grateful to Profs. Vtyurin BM and Medvedev VS, Medical Radiological Research
               Center, Obninsk, as well as to Dr. Choporov Yu, Head of the Forensic Medicine Department of City
               Hospital, Obninsk, for supplying thyroid samples. We are also grateful to Dr. Karandaschev V, Dr. Nosenko
               S, and Moskvina I, Institute of Microelectronics Technology and High Purity Materials, Chernogolovka,
               Russia, for their help in ICP-MS analysis.


               Authors’ contributions
               Collected thyroid samples, designed the INAA and ICP-AES of samples, carried out the statistical analysis of
               results: Zaichick V
               Managed the literature searches, wrote the first draft of the manuscript, translated the manuscript into
               English: Zaichick S
               Read and approved the final manuscript: Zaichick V, Zaichick S


               Availability of data and materials
               Data were obtained in Radionuclide Diagnostic Department, Medical Radiological Research Center,
               Obninsk 249036, Russia. The data are available in electronic format as Excel and Word files upon request.
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