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Page 10 of 15 Zaichick et al. J Cancer Metastasis Treat 2018;4:60 I http://dx.doi.org/10.20517/2394-4722.2018.52

transformed thyroid cell - mass of follicular colloid”. Nevertheless, the accumulation of K in neoplastic
thyroids could possibly be explored for diagnosis of TC.

Mg
Mg is abundant in the human body. This element is essential for the functions of more than 300 enzymes
(e.g., alkaline phosphatases, ATP-ases, phosphokinases, the oxidative phosphorylation pathway). It plays a
crucial role in many cell functions such as energy metabolism, protein and DNA syntheses, and cytoskeleton
activation. Moreover, Mg plays a central role in determining the clinical picture associated with thyroid
[99]
disease . Experimental data have shown that high doses of magnesium increase the activity of the thyroid
gland [100] . Magnesium deficiency can influence bioavailability and tissue distribution of selenium which
then appears diminished [101] . From these data, one can conclude that Mg is involved in the thyroid function.
If so, significant reduction in Mg content can be associate with TC, because malignant transformation is
accompanied by a loss of thyroid-specific functional features. However, it is well known that malignant
tumors usually have higher Mg levels than normal tissues [102-107] , possibly caused by the “retention” of Mg
by the tumor [108] , as a result of the high Mg requirement of growing cells. In addition, cultured proliferating
cells have long been known to contain more magnesium than quiescent cells, and experimental conditions
that decreased magnesium availability affected cell proliferation rate [109] . Thus, the elevated levels of Mg in
neoplastic thyroids could possibly be explored for the diagnosis of TC.

Mn
The trace element Mn is a cofactor for numerous enzymes, playing many functional roles in living
organisms. The Mn-containing enzyme, Mn-SOD, is the principal antioxidant enzyme which neutralizes
the toxic effects of reactive oxygen species (ROS). It has been speculated that Mn interferes with thyroid
hormone binding, transport, and activity at the tissue level [110] . There is the opinion that Mn deficiencies
in humans are rare and humans maintain stable tissue levels of this trace element [111] . It was reported that
intracellular Mn content was positively correlated with Mn-SOD, suggesting that the intracellular Mn
level is associated with Mn-SOD activity [112] . However, an overall comprehension of Mn homeostasis and
physiology, which is not yet acquired, is mandatory to establish Mn exact role in the thyroid malignant
tumors etiology and metabolism. Anyway, the accumulation of Mn in neoplastic thyroids could possibly be
explored for diagnosis of TC.

Na
The knowledge concerning ion regulation in many normal and abnormal cell processes has had a rapid
development. It was found, among other regulations, that sodium-calcium exchange is associated with
the cytoskeleton and the cell membrane. A hypothesis was eventually established that a wide variety of
pathological phenomena ranging from acute cell death to chronic processes, such as neoplasia, have a
common series of cellular reactions [113] . In accordance with this hypothesis, concentrations of sodium
were found to be enhanced in human and animal neoplastic tissues [114,115] . Moreover, the hypothesis that
physiological and biochemical changes are associated with proliferating malignant tumors may cause an
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increase in total tissue sodium concentration was tested with non-invasive, quantitative Na magnetic
resonance imaging in patients with benign and malignant breast tumors. It was shown that elevated Na
concentrations in breast lesions appear to be a cellular-level indicator associated with malignancy [116] . In
addition, Na is mainly an extracellular electrolyte and its elevated level in malignant tumors might be linked
with a high tumor vascularization (see Chlorine). Anyway, it seems that the accumulation of Na is a generic
property of malignant tumors.

P
P is necessary for several, various biological roles in the signal transduction of cells and energy exchange of
human body. About 80%-90% of phosphorus is founded in teeth and bones in the form of hydroxyapatite.