Abstract
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.
Highlights
Thyroid cancer (TC) is the most common endocrine carcinoma, constituting over 95%of endocrine cancers and 3.4% of all carcinomas diagnosed annually all over the world [1].The incidence of thyroid cancers (TCs) has tripled within last 35 years in western European countries [2].thyroid cancer incidence in the United States between 1974–2013 increased, on average, 3.6% per year [3]
As opposed to common rationale, that glycation occurs mainly intracellularly, it has been shown that TCs, regardless associated with inflammation, inactivation of enzymatic antioxidants, modifications of of whether benign or malignant, are associated with intense glycation, the mivarious proteins, lipid croenvironment of TCs was more prone to this process, compared to tumor cells [121]
Advanced glycation end-products (AGEs), precursors of AGEs, RAGE, and RAGE ligands not being AGEs are all engaged in TCs carcinogenesis, playing different roles during its various stages
Summary
Thyroid cancer (TC) is the most common endocrine carcinoma, constituting over 95%. of endocrine cancers and 3.4% of all carcinomas diagnosed annually all over the world [1]. Apart from the increase of TCs incidence, an increase in mortality associated with TCs could be seen, since, during 1994–2013, the incidence-based mortality increased 1.1% per year (95% confidence interval 0.6–1.6%) [3] These observations may indicate that an evolution of thyroid cancer biology may have an impact on both its incidence rate and its related mortality. According to the World Health Organization classification, malignant thyroid cancers can be divided into five main histological types [4]: papillary (PTC), follicular (FTC), poorly differentiated (PDTC), medullary (MTC), and anaplastic (ATC).
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