Characteristic Hallmarks of Aging and the Impact on Carcinogenesis.

Evidence shows that there is a synergistic, bidirectional association between cancer and aging with many shared traits. Age itself is a risk factor for the onset of most cancers, while evidence suggests that cancer and its treatments might accelerate aging by causing genotoxic and cytotoxic insults. Aging has been associated with a series of alterations that can be linked to cancer: i) genomic instability caused by DNA damage or epigenetic alterations coupled with repair errors, which lead to progressive accumulation of mutations; ii) telomere attrition with possible impairment of telomerase, shelterin complex, or the trimeric complex (Cdc13, Stn1 and Ten1 - CST) activities associated with abnormalities in DNA replication and repair; iii) altered proteostasis, especially when leading to an augmented proteasome, chaperon and autophagy-lysosome activity; iv) mitochondrial dysfunction causing oxidative stress; v) cellular senescence; vi) stem cells exhaustion, intercellular altered communication and deregulated nutrient sensing which are associated with microenvironmental modifications which may facilitate the subsequential role of cancer stem cells. Nowadays, anti-growth factor agents and epigenetic therapies seem to assume an increasing role in fighting aging-related diseases, especially cancer. This report aims to discuss the impact of age on cancer growth.

Hearing Loss After Cisplatin-based Chemoradiotherapy for Locally Advanced Head and Neck Cancer: A Prospective Single-institution Study.

BACKGROUND/AIM: A single-institution prospective study was conducted to evaluate hearing loss rate after intensity modulated radiotherapy with concomitant cisplatin-based chemotherapy (CRT) for locally advanced head and neck cancer and identify cochlear dosimetric parameters associated with hearing loss risk. PATIENTS AND METHODS: Hearing assessment, patients' characteristics, tumor-related variables, and cochlear quantitative dosimetric factors for adults with locally advanced head and neck cancer treated with CRT were prospectively collected. Each patient repeated audiometry at baseline (pre-CRT), 1 month after CRT, and then every 3 to 6 months. For each cochlea minimum dose (Dmin), mean dose (Dmean), and maximum dose (Dmax) were extracted from treatment plans. Logistic analysis was used for multivariate modeling. The relation between cochlear dosimetric factors and significant hearing loss was also analyzed with receiver operating characteristic (ROC) curves. RESULTS: Between January 2016 and December 2018, 35 patients (70 cochleae) were included. Most patients (n=29; 82.9%) had primary cancer in a low-risk region (oral cavity, oropharynx, larynx). All patients completed the programmed CRT. During follow-up, significant hearing loss was recorded in 13 cases (37.1%). The ROC areas for significant hearing loss in relation to Dmin, Dmean, and Dmax were 0.70, 0.66, and 0.66, respectively. A dose-dependent relationship was noted between cochlear Dmin and significant hearing loss. CONCLUSION: Dmin <14.4 Gy is associated with reduced rates of significant hearing loss after concomitant cisplatin-based CRT in patients with locally advanced head and neck cancer.

Anti-inflammatory role of curcumin in retinal disorders (Review).

Curcumin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-hepta-1,6-diene-3,5-dione], the main component of turmeric (Curcuma longa, a flowering plant of the ginger family, Zingiberaceae), is known to possess different pharmacological activities, particularly anti-inflammatory and antioxidant properties. Since an underlying inflammatory process exists in several ocular conditions, such as anterior uveitis, glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR), the aim of the present review was to summarize the pleiotropic effects exerted by this molecule, focusing in particular on its beneficial role in retinal diseases. The anti-inflammatory activity of curcumin has also been described in numerous systemic inflammatory pathologies and tumors. Specifically, the biological, pharmaceutical and nutraceutical properties of curcumin are associated with its ability to downregulate the expression of the following genes: IκBα, cyclooxygenase 2, prostaglandin E2, interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor-α. According to this finding, curcumin may be useful in the treatment of some retinal disorders. In DR, proliferative vitreoretinopathy and AMD, beneficial effects have been observed following treatment with curcumin, including slowing down of the inflammatory process. Despite the aforementioned evidence, the main disadvantage of this substance is that it possesses a low solubility, as well as poor oral bioavailability due to its reduced absorption, rapid metabolism and rapid elimination. Therefore, several curcumin analogues have been synthesized and tested over the years, in order to improve the possible obtainable therapeutic effects. The purpose of the present review was to identify new aspects that could guide future research on this important traditional medicine, which is a well-tolerated natural product, and is widely considered safe and economical.