RESUMO
To date, thyroid cancers (TCs) remain a clinical challenge owing to their heterogeneous nature. The etiopathology of TCs is associated not only with genetic mutations or chromosomal rearrangements, but also non-genetic factors, such as oxidative-, nitrosative-, and carbonyl stress-related alterations in tumor environment. These factors, through leading to the activation of intracellular signaling pathways, induce tumor tissue proliferation. Interestingly, the incidence of TCs is often coexistent with various simultaneous mutations. Advanced glycation end-products (AGEs), their precursors and receptors (RAGEs), and other ligands for RAGEs are reported to have significant influence on carcinogenesis and TCs progression, inducing gene mutations, disturbances in histone methylation, and disorders in important carcinogenesis-related pathways, such as PI3K/AKT/NF-kB, p21/MEK/MPAK, or JAK/STAT, RAS/ERK/p53, which induce synthesis of interleukins, growth factors, and cytokines, thus influencing metastasis, angiogenesis, and cancer proliferation. Precursors of AGE (such as methylglyoxal (MG)) and selected ligands for RAGEs: AS1004, AS1008, and HMGB1 may, in the future, become potential targets for TCs treatment, as low MG concentration is associated with less aggressive anaplastic thyroid cancer, whereas the administration of anti-RAGE antibodies inhibits the progression of papillary thyroid cancer and anaplastic thyroid cancer. This review is aimed at collecting the information on the role of compounds, engaged in glycation process, in the pathogenesis of TCs. Moreover, the utility of these compounds in the diagnosis and treatment of TCs is thoroughly discussed. Understanding the mechanism of action of these compounds on TCs pathogenesis and progression may potentially be the grounds for the development of new treatment strategies, aiming at quality-of-life improvements.
RESUMO
The patho-mechanism of changes in the thyroid gland, including carcinogenesis, is a complex process, which involves oxidative stress. The goal of our investigation was to verify the extent of stress in the thyroid gland related to glycation. The study samples were comprised of blood sera, thyroid, and adipose tissue sections probed from 37 patients diagnosed with thyroid cancers and goiter. Using immuno-enzymatic and fluorometric assays we analyzed the content of advanced glycation end-products (AGEs), pentosidine, receptors for advanced glycation end-products (RAGE), scavenger receptor class (SR)-A, SR-B, glutathione, malondialdehyde and nitric oxide synthase. In addition to classic AGEs, a recent study detected the melibiose-derived glycation (MAGE) product. We demonstrated the presence of AGEs, MAGE and their receptors of the RAGE and SR-A. In addition, in the control samples of thyroid glands SR-B groups were detected as well as of pathological groups without noticeable tendency to antigen concentration in the area of carcinogenesis. Fluorescent AGEs correlate positively with glutathione, which supports the assumption that glycation stress leads to augmentation of oxidative stress and increase of the intensity of antioxidant mechanisms.
