Alterations in the amino acid profile in patients with papillary thyroid carcinoma with and without Hashimoto’s thyroiditis

PurposeAmino acids (AAs) play important physiological roles in living cells. Some amino acid changes in blood are specific for autoimmune disorders, and some are specific for thyroid cancer. The aims of this study were to profile AA metabolites in the serum of patients with papillary thyroid carcinoma (PTC0) without Hashimoto’s thyroiditis (HT) and patients with PTC with HT (PTC1) and predict whether AA metabolites are associated with thyroid disease, thyroid hormone and thyroid autoantibodies.MethodsA total of 95 serum samples were collected, including 28 healthy controls (HCs), 28 PTC0 patients and 39 PTC1 patients. Serum samples were analyzed by high-performance liquid chromatography-triple stage quadrupole-mass spectrometry (HPLC-TSQ-MS), and twenty-one amino acids (AAs) were detected.ResultsThe serum concentration of glutamic acid was significantly elevated in PTC1 patients compared with PTC0 patients. Lysine was the second amino acid that differentiated these two groups of PTC patients. In addition, the serum concentrations of glycine, alanine and tyrosine were significantly reduced in both PTC patient groups compared to the HC group. These AAs were also correlated with thyroid hormones and antibodies. Five amino acid markers, namely, glycine, tyrosine, glutamic acid, glutamine and arginine, separated/distinguished PTC0 patients from healthy subjects, and eight AA markers, the same AAs as above without arginine but with alanine, leucine, valine and histidine, separated/distinguished PTC1 patients from healthy subjects based on ROC analysis.ConclusionCompared with the HCs, changes in AAs in PTC0 and PTC1 patients showed similar patterns, suggesting the possibility of a common pathophysiological basis, which confirms preliminary research that PTC is significantly associated with pathologically confirmed HT. We found two AAs, lysine and alanine, that can perform diagnostic functions in distinguishing PTC1 from PTC0

Table_1_Alterations in the amino acid profile in patients with papillary thyroid carcinoma with and without Hashimoto’s thyroiditis.doc

PurposeAmino acids (AAs) play important physiological roles in living cells. Some amino acid changes in blood are specific for autoimmune disorders, and some are specific for thyroid cancer. The aims of this study were to profile AA metabolites in the serum of patients with papillary thyroid carcinoma (PTC0) without Hashimoto’s thyroiditis (HT) and patients with PTC with HT (PTC1) and predict whether AA metabolites are associated with thyroid disease, thyroid hormone and thyroid autoantibodies.MethodsA total of 95 serum samples were collected, including 28 healthy controls (HCs), 28 PTC0 patients and 39 PTC1 patients. Serum samples were analyzed by high-performance liquid chromatography-triple stage quadrupole-mass spectrometry (HPLC-TSQ-MS), and twenty-one amino acids (AAs) were detected.ResultsThe serum concentration of glutamic acid was significantly elevated in PTC1 patients compared with PTC0 patients. Lysine was the second amino acid that differentiated these two groups of PTC patients. In addition, the serum concentrations of glycine, alanine and tyrosine were significantly reduced in both PTC patient groups compared to the HC group. These AAs were also correlated with thyroid hormones and antibodies. Five amino acid markers, namely, glycine, tyrosine, glutamic acid, glutamine and arginine, separated/distinguished PTC0 patients from healthy subjects, and eight AA markers, the same AAs as above without arginine but with alanine, leucine, valine and histidine, separated/distinguished PTC1 patients from healthy subjects based on ROC analysis.ConclusionCompared with the HCs, changes in AAs in PTC0 and PTC1 patients showed similar patterns, suggesting the possibility of a common pathophysiological basis, which confirms preliminary research that PTC is significantly associated with pathologically confirmed HT. We found two AAs, lysine and alanine, that can perform diagnostic functions in distinguishing PTC1 from PTC0.</p

Changes in hypoxia level of CT26 tumors during various stages of development and comparing different methods of hypoxia determination.

The aim of this study was to evaluate hypoxia level at various tumor developmental stages and to compare various methods of hypoxia evaluation in pre-clinical CT26 tumor model. Using three methods of hypoxia determination, we evaluated hypoxia levels during CT26 tumor development in BALB/c mice from day 4 till day 19, in 2-3 days intervals. Molecular method was based on the analysis of selected genes expression related to hypoxia (HIF1A, ANGPTL4, TGFB1, VEGFA, ERBB3, CA9) or specific for inflammation in hypoxic sites (CCL2, CCL5) at various time points after CT26 cancer cells inoculation. Imaging methods of hypoxia evaluation included: positron-emission tomography (PET) imaging using [18F]fluoromisonidazole ([18F]FMISO) and a fluorescence microscope imaging of pimonidazole (PIMO)-positive tumor areas at various time points. Our results showed that tumor hypoxia at molecular level was relatively high at early stage of tumor development as reflected by initially high HIF1A and VEGFA expression levels and their subsequent decrease. However, imaging methods (both PET and fluorescence microscopy) showed that hypoxia increased till day 14 of tumor development. Additionally, necrotic regions dominated the tumor tissue at later stages of development, decreasing the number of hypoxic areas and completely eliminating normoxic regions (observed by PET). These results showed that molecular methods of hypoxia determination are more sensitive to show changes undergoing at cellular level, however in order to measure and visualize hypoxia in the whole organ, especially at later stages of tumor development, PET is the preferred tool. Furthermore we concluded, that during development of tumor, two peaks of hypoxia occur