p53 Mutation Spectrum (Occurrence) and Load (Genotype Damage) in Ulcerative Colitis

Principal Investigator: Guang-Yu Yang, MD Chronic inflammation is an important risk factor for cancer. Patients with ulcerative colitis (UC) face a significantly increased risk of developing colorectal cancers. Damaged DNA and genetic alterations can be caused by the inflammatory process. Identifying crucial inflammation-associated molecular events offers potential targets to predict and prevent cancers. Missense p53 mutations are one of the most common and earliest molecular events seen in UC-associated carcinogenesis. Yet little is known about the evolution of p53 mutations during the long-term course of UC and whether targeting these mutations will have an impact on the long-term cancer risk in patients with UC. Employing a next-generation sequencing approach, Dr. Yang’s study aims to determine the mutation spectrum and load of the p53 gene in this patient population. The researchers intend to identify whether specific p53 mutations are critical in driving UC-induced carcinogenesis, and to evaluate its role as an efficient biomarker for predicting the risk of cancer development in UC...

Inflammatory Lipid Signaling and Eosinophilic Esophagitis

Principal Investigator: Guang-Yu Yang, MD, PhD Most patients with Eosinophilic Esophagitis (EoE) experience an abnormal immune-mediated response to food antigens. Identifying unique biomarkers involved in the pathogenesis of allergic inflammation could significantly improve treatments. The conversion of cell membrane arachidonic acid to ω-6 prostaglandin and ω-6 leukotriene eicosanoids during the inflammatory cascade provides many potential drug targets to impede the inflammatory process in patients with EoE. ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) have opposing influences on inflammation. Currently, there is no study on PUFA metabolism and the role these PUFAs metabolites play in the pathogenesis of EoE. Dr. Yang’s study aims to determine the ω-3 and ω-6 PUFAs metabolites/eicosanoids profile in eosinophilic esophagitis using a liquid chromatography tandem mass spectrometry (LC-MS/MS)-based metabolomics approach and to identify the unique eicosanoids or biomarker/s for diagnosis, prognosis and monitoring the therapeutic effect on...

How to Optimize Control of Acid Reflux to Reduce the Risk of Cancers in Barrett’s Esophagus

Barrett’s Esophagus (BE) occurs when damaging acid reflux causes the lining of the esophagus to change from normal to pre-cancerous tissue. Although BE can be effectively treated with acid-blocking medications, some patients with more advanced disease often require endoscopic therapy to remove the abnormal tissue. While many experience successful outcomes with this treatment option, some 5 to 25 percent will redevelop the disease; recurrence puts patients at increasing high risk for esophageal cancer or adenocarcinoma. With a five-year survival rate of about 20 percent, this deadly cancer has increased by a factor of more than seven in the past 40 years. Many risk factors contribute to BE, including gender, with men are at higher risk than women; chronic heartburn and acid reflux, especially before age 30; and smoking. Interesting, the disorder has developed with increasing frequency in non-smoking young men between the ages of 20 to 45. Sri Komanduri, MD, Director of Interventional Endoscopy at Northwestern Medicine and his research team previously found that persistent acid reflux in patients who have undergone endoscopic therapy likely causes recurrent BE. Currently, these patients must undergo placement of an uncomfortable transnasal catheter over a 24-hour period to assess and measure persistent acid reflux. This testing helps gastroenterology specialists to determine the best treatment options: a combination of medications and endoscopic treatment or perhaps a referral for surgery. Due to costs and patient intolerance, though, this type of reflux testing has proven to be impractical. Studies of patients without endoscopically-treated BE have suggested consistent changes in the lining of esophageal biopsy samples, which strongly indicate uncontrolled acid reflux. Extrapolating from this observation, Dr....