Comparing survival outcomes in early stage desmoplastic melanoma with or without adjuvant radiation.

Desmoplastic melanoma (DM) due to its rare and locally aggressive nature, can be difficult to study and to treat effectively. Whether the optimal treatment approach for these tumors should include adjuvant radiation has been unclear in the literature. In this retrospective study of the National Cancer Database, 2390 patients with localized DM were included for analysis. 2082 were treated with wide local excision (WLE) and 308 were treated with wide local excision and adjuvant radiation therapy (WLE + RT). Overall survival (OS) in these groups was compared on crude and adjusted analyses utilizing Cox proportional hazards regression modeling. There was no difference in OS at 1, 3, and 5 years on initial analysis. Subsequent multivariate analysis and propensity score analysis showed a survival benefit in those treated with WLE + RT. Multivariate analysis demonstrated significantly decreased OS in cases of residual tumor following surgical excision. Adjuvant radiation was more likely to be performed for tumors on the head and neck, tumors with higher pathologic American Joint Committee on Cancer stage and T classifications, and tumors with positive surgical margins. This is the first study to demonstrate significantly improved OS in early-stage DM patients treated with WLE + RT compared to WLE alone.

Phytochemical antioxidants modulate mammalian cellular epigenome: implications in health and disease.

UNLABELLED: In living systems, the mechanisms of inheritance involving gene expression are operated by (i) the traditional model of genetics where the deoxyribonucleic acid (DNA) transcription and messenger ribonucleic acid stability are influenced by the DNA sequences and any aberrations in the primary DNA sequences and (ii) the epigenetic (above genetics) model in which the gene expression is regulated by mechanisms other than the changes in DNA sequences. The widely studied epigenetic alterations include DNA methylation, covalent modification of chromatin structure, state of histone acetylation, and involvement of microribonucleic acids. SIGNIFICANCE: Currently, the role of cellular epigenome in health and disease is rapidly emerging. Several factors are known to modulate the epigenome-regulated gene expression that is crucial in several pathophysiological states and diseases in animals and humans. Phytochemicals have occupied prominent roles in human diet and nutrition as protective antioxidants in prevention/protection against several disorders and diseases in humans. RECENT ADVANCES: However, it is beginning to surface that the phytochemical phenolic antioxidants such as polyphenols, flavonoids, and nonflavonoid phenols function as potent modulators of the mammalian epigenome-regulated gene expression through regulation of DNA methylation, histone acetylation, and histone deacetylation in experimental models. CRITICAL ISSUES AND FUTURE DIRECTIONS: The antioxidant or pro-oxidant actions and their involvement in the epigenome regulation by the phytochemical phenolic antioxidants should be at least established in the cellular models under normal and pathophysiological states. The current review discusses the mechanisms of modulation of the mammalian cellular epigenome by the phytochemical phenolic antioxidants with implications in human diseases.