DNA oxidative damage in oral cancer: 8-hydroxy-2´-deoxyguanosine immunoexpression assessment

Background: The development and establishment of oral squamous cell carcinoma are confined to carcinogenesis, which involves oxidative stress via oxygen-free radical production as a hydroxyl radical (HO•), considered the most important cause of oxidative damage to basic biomolecules since it targets DNA strands. 8-Hydroxy-2´- deoxyguanosine (8-OHdG) is considered a free radical with a promutagenic capacity due to its ability to pair with adenosine instead of cytosine during replication. Material and Methods: We collected 30 paraffin-embedded tissue samples of OSCC from patients treated between 2013 and 2018. We recorded risk habits, disease stage, disease free survival and death with at least 3 years of followup. 8-Hydroxyguanosine was evaluated by immunohistochemistry and subsequently classified as weak-moderate or strong positive expression. Additionally, we noted whether it was expressed in the cytoplasm and/or nucleus. Results: Most of the cases expressed 8-OHdG with a strong intensity (80%). All neoplastic cells were preferentially stained in only the cytoplasm (70.0%), but nuclear positivity was found in 30%, independent of the intensity. Based on the location in the cytoplasm and/or nucleus, tumors >4 cm showed a high frequency (95.5%) of 8-OHdG expression in only the cytoplasm, with a significant difference (p value ≤ 0.001). Additionally, overall survival was affected when immunoexpression was present in the cytoplasm and nucleus because all deaths were in this group were statistically significant (p value = 0.001). Conclusions: All tumors showed DNA oxidative damage, and 8-OHdG was preferentially expressed in the cytoplasm. This finding was associated with tumor size and, when present in the nucleus, might also be related to death. (AU)

Implications of receptor for advanced glycation end products for progression from obesity to diabetes and from diabetes to cancer.

Obesity and type 2 diabetes mellitus (T2DM) are chronic pathologies with a high incidence worldwide. They share some pathological mechanisms, including hyperinsulinemia, the production and release of hormones, and hyperglycemia. The above, over time, affects other systems of the human body by causing tissue hypoxia, low-grade inflammation, and oxidative stress, which lay the pathophysiological groundwork for cancer. The leading causes of death globally are T2DM and cancer. Other main alterations of this pathological triad include the accumulation of advanced glycation end products and the release of endogenous alarmins due to cell death (i.e., damage-associated molecular patterns) such as the intracellular proteins high-mobility group box protein 1 and protein S100 that bind to the receptor for advanced glycation products (RAGE) - a multiligand receptor involved in inflammatory and metabolic and neoplastic processes. This review analyzes the latest advanced reports on the role of RAGE in the development of obesity, T2DM, and cancer, with an aim to understand the intracellular signaling mechanisms linked with cancer initiation. This review also explores inflammation, oxidative stress, hypoxia, cellular senescence, RAGE ligands, tumor microenvironment changes, and the "cancer hallmarks" of the leading tumors associated with T2DM. The assimilation of this information could aid in the development of diagnostic and therapeutic approaches to lower the morbidity and mortality associated with these diseases.