Cancer development, progression, and therapy: an epigenetic overview.

Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell-cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, including histone modifications, DNA methylation, and DNA hydroxymethylation, can modify these characteristics. Targets for these epigenetic changes include signaling pathways that regulate apoptosis and autophagy, as well as microRNA. We propose that predisposed normal cells convert to cancer progenitor cells that, after growing, undergo an epithelial-mesenchymal transition. This process, which is partially under epigenetic control, can create a metastatic form of both progenitor and full-fledged cancer cells, after which metastasis to a distant location may occur. Identification of epigenetic regulatory mechanisms has provided potential therapeutic avenues. In particular, epigenetic drugs appear to potentiate the action of traditional therapeutics, often by demethylating and re-expressing tumor suppressor genes to inhibit tumorigenesis. Epigenetic drugs may inhibit both the formation and growth of cancer progenitor cells, thus reducing the recurrence of cancer. Adopting epigenetic alteration as a new hallmark of cancer is a logical and necessary step that will further encourage the development of novel epigenetic biomarkers and therapeutics.

An Exploration of System-Level Factors and the Geographic Variation in Bariatric Surgery Utilization.

There is wide geographic variation in bariatric surgery rates, although higher regional rates of obesity are not correlated with higher rates of surgery. In this study, four system-level factors were explored as contributors to this geographic variation. Geographic utilization rates of bariatric surgery showed no correlation to the number of bariatric surgeons, number of accredited centers, and the percentage of patients with a recent primary care visit. The total number of surgical discharges was weakly correlated with bariatric surgery rates (r = 0.26, p = <0.001). As surgeon supply, accredited bariatric centers, overall surgical volume, and access to primary care do not appear to heavily influence bariatric surgery rates, future studies are needed to identify additional factors that may explain the underutilization of bariatric surgery.