Such improvements represent the means to greatly increase the relevance of this model to investigate skeletal muscle disease states
since it allows observations made in vitro to be scaled, producing accurate predictions of in vivo responses. Furthermore, an ability to scale up observed in vitro responses based on physical parameters facilitates the tailoring of drug treatment dosages to an individual’s muscle mass and may have significant applications Inhibitors,research,lifescience,medical in the development of personalized treatment regimes. Finally, LY294002 in vitro improved predictions of in vivo responses from in vitro data are likely to accelerate future drug development and toxicology studies since greater power can be obtained in early pre-clinical screens. Acknowledgments This work was supported by NIH Grant Nos. R01NS050452 and R01EB009429. Special thanks to Mandy Esch
for aiding microfabrication.
In the United States alone nearly 18,000 new esophageal cancers are diagnosed and more than 15,000 deaths Inhibitors,research,lifescience,medical occur each year, illustrating the high mortality of this disease and the ongoing need for improved treatment strategies (1). Randomized controlled trials comparing neoadjuvant chemoradiotherapy (NAC) Inhibitors,research,lifescience,medical with surgery alone have demonstrated statistically significant improvements in overall survival (OS) (2-5). More recently, the CROSS trial modified traditional chemotherapy protocols, introducing weekly administration of carboplatin and paclitaxel with concomitant radiotherapy. This resulted in a clear OS benefit for NAC versus surgery alone, with a median OS of 49.3 versus 24 months, respectively (5). These studies are consistent with several meta-analyses, which demonstrate that NAC significantly increases OS compared to Inhibitors,research,lifescience,medical surgery alone (6-9). Taken together, these studies highlight the utility of NAC in the treatment of esophageal cancer. In addition to providing a clear survival benefit, NAC increases the likelihood of an R0 resection (6), which is associated with Inhibitors,research,lifescience,medical significantly improved OS in patients
with esophageal cancer (10). Importantly, the pathologic stage following esophagectomy in patients treated with NAC is a strong predictor of OS, and in particular, downstaging by NAC is associated with improved disease-free survival (DFS) and OS (11). Additional studies have demonstrated that patients with a pathologic complete response (pCR) following NAC and esophagectomy have high long-term OS rates (12,13). Based on these and other data, multimodality Phosphoprotein phosphatase treatment including NAC followed by esophagectomy has been established as standard of care for early stage (II-III), resectable esophageal cancer and that patients treated with NAC are more likely to have an R0 resection and pCR, more likely to be downstaged, and have improved DFS and OS. Therefore, the specific aim of the current study was to analyze OS outcomes of NAC at a single, tertiary care academic medical center.