An in vitro co-culture model of esophageal cells identifies ascorbic acid as a modulator of cell competition

<p>Abstract</p> <p>Background</p> <p>The evolutionary dynamics between interacting heterogeneous cell types are fundamental properties of neoplastic progression but can be difficult to measure and quantify. Cancers are heterogeneous mixtures of mutant clones but the direct effect of interactions between these clones is rarely documented. The implicit goal of most preventive interventions is to bias competition in favor of normal cells over neoplastic cells. However, this is rarely explicitly tested. Here we have developed a cell culture competition model to allow for direct observation of the effect of chemopreventive or therapeutic agents on two interacting cell types. We have examined competition between normal and Barrett's esophagus cell lines, in the hopes of identifying a system that could screen for potential chemopreventive agents.</p> <p>Methods</p> <p>One fluorescently-labeled normal squamous esophageal cell line (EPC2-hTERT) was grown in competition with one of four Barrett's esophagus cell lines (CP-A, CP-B, CP-C, CP-D) under varying conditions and the outcome of competition measured over 14 days by flow cytometry.</p> <p>Results</p> <p>We demonstrate that ascorbic acid (vitamin C) can help squamous cells outcompete Barrett's cells in this system. We are also able to show that ascorbic acid's boost to the relative fitness of squamous cells was increased in most cases by mimicking the pH conditions of gastrointestinal reflux in the lower esophagus.</p> <p>Conclusions</p> <p>This model is able to integrate differential fitness effects on various cell types, allowing us to simultaneously capture effects on interacting cell types without having to perform separate experiments. This model system may be used to screen for new classes of cancer prevention agents designed to modulate the competition between normal and neoplastic cells.</p

Chronotype and Psychiatric Disorders

Purpose of ReviewChronotype, reflecting interindividual differences in daily activity patterns and sleep-wake cycles, is intrinsically connected with well-being. Research indicates increased risk of many adverse mental health outcomes for evening-type individuals. Here, we provide an overview of the current evidence available on the relationship between chronotype and psychiatric disorders.Recent FindingsThe association between eveningness and depression is well established cross-sectionally, with preliminary support from longitudinal studies. The mechanisms underlying this relationship warrant further research; deficient cognitive-emotional processes have recently been implicated. Eveningness is associated with unhealthy lifestyle habits, and the propensity of evening types to addiction has been recognized. Chronotype may also be implicated in disordered eating.SummaryEveningness is associated with depression—including seasonal affective disorder (SAD)—and substance dependence, while support for a relation with anxiety disorders and psychosis is lacking. In bipolar disorder, chronotype is linked to depression but not mania. Eveningness is also related to sleep disturbances and poor lifestyle habits, which may increase risk for psychiatric disorders.FSW - Self-regulation models for health behavior and psychopathology - ou