Non-steroidal anti-inflammatory drugs (NSAIDs) are being tested extensively for their role in the treatment and prevention of several cancers. Typically NSAIDs exhibit anti-tumor activities via modulation of cyclooxygenase (COX)-dependent mechanisms, however, an anti-cancer NSAID tolfenamic acid (TA) is believed to work through COX-independent pathways. Results from our laboratory and others have demonstrated the anti-cancer activity of TA in various cancer models including pancreatic cancer. TA has been shown to modulate certain cellular processes including, apoptosis, reactive oxygen species and signaling. In this study, molecular profiling was performed to precisely understand the mode of action of TA. Three pancreatic cancer cell lines, L3.6pl, MIA PaCa-2, and Panc1 were treated with TA (50 μM for 48 h) and the changes in gene expression was evaluated using the Affymetrix GeneChip Human Gene ST Array platform. Microarray results were further validated using quantitative PCR for seven genes altered by TA treatment in all three cell lines. Functional analysis of differentially expressed genes (2 fold increase or decrease, p < 0.05) using Ingenuity Pathway Analysis software, revealed that TA treatment predominantly affected the genes involved in cell cycle, cell growth and proliferation, and cell death and survival. Promoter analysis of the differentially expressed genes revealed that they are enriched for Sp1 binding sites, suggesting that Sp1 could be a major contributor in mediating the effect of TA. The gene expression studies identified new targets involved in TA's mode of action, while supporting the hypothesis about the association of Sp1 in TA mediated effects in pancreatic cancer.

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Patients with inflammatory bowel disease often present to the emergency department due to the chronic relapsing nature of the disease. Previous studies have shown younger patients to have an increased frequency of emergency department visits, resulting in repeated exposure to imaging studies and steroids, both of which are associated with risks. We performed a retrospective cohort analysis of inflammatory bowel disease patients seen at Houston Methodist Hospital’s emergency department from January 2014 to December 2017 using ICD codes to identify patients with Crohn’s disease, ulcerative colitis, or indeterminate colitis from the electronic medical record. Data were collected on demographics, medications, and imaging. Five hundred and fifty-nine patients were randomly selected for inclusion. Older age was associated with decreased risk of CT scan or steroid use. Patients with ulcerative colitis compared to Crohn’s had decreased risk of CT scan, while there was an increased risk of CT in patients on a biologic, immunomodulator, or when steroids were given. Steroid use was also more common in those with inflammatory bowel disease as the primary reason for the visit. Patients in our study frequently received steroids and had CT scans performed. The increased risk of CT in those on a biologic, immunomodulator, or steroids suggests more severe disease may contribute. Guidelines are needed to reduce any unnecessary corticosteroid use and limit repeat CT scans in young inflammatory bowel disease patients to decrease the risk of radiation-associated malignancy over their lifetime.