Cannabinoid Hyperemesis Encounters After Medical Legalization in Oklahoma.

Introduction Medical cannabis has recently become legal in Oklahoma. Cannabinoid hyperemesis syndrome (CHS) is severe nausea, vomiting, and often abdominal pain typically seen in heavy users of cannabis. The aim of this study is to determine whether emergency department (ED) diagnoses of CHS have increased after medical legalization. Methods We performed a retrospective chart review study of equivalent time periods prior to and after the first legal sales of medical cannabis in Oklahoma. Data were gathered from a single urban ED of adult patients with diagnosed or suspected CHS. We analyzed data using a chi-square analysis of CHS cases as a proportion of total ED visits. Results Diagnosed and suspected CHS visits increased from 43 cases in the eight months preceding the first legal sale to 62 cases in the eight months after legalization. This represents a statistically significant increase in ED visits for CHS (p = 0.026). Total ED encounters were 30,437 and 28,362, respectively, during those time periods. The proportion of visits for CHS was much higher (220/100000 vs 13.3/100000) than previously reported in the literature. The pre-legalization and post-legalization groups did not differ by age, sex, history of GI illness and diabetes, pregnancy, or other drug use. Conclusion We observed a statistically significant increase in ED visits for CHS after the first legal sales of medical cannabis in Oklahoma. Our high proportion of ED visits for CHS could be related to study design, increased provider awareness, high THC levels in Oklahoma's medical cannabis, or increased numbers of cannabis users after legalization. Increases in ED visits for CHS and other cannabinoid-related illnesses must be weighed against the positive effects for cannabis users by policymakers.

Auranofin Protects Intestine against Radiation Injury by Modulating p53/p21 Pathway and Radiosensitizes Human Colon Tumor.

PURPOSE: The radiosensitivity of the normal intestinal epithelium is the major limiting factor for definitive radiotherapy against abdominal malignancies. Radiosensitizers, which can be used without augmenting radiation toxicity to normal tissue, are still an unmet need. Inhibition of proteosomal degradation is being developed as a major therapeutic strategy for anticancer therapy as cancer cells are more susceptible to proteasomal inhibition-induced cytotoxicity compared with normal cells. Auranofin, a gold-containing antirheumatoid drug, blocks proteosomal degradation by inhibiting deubiquitinase inhibitors. In this study, we have examined whether auranofin selectively radiosensitizes colon tumors without promoting radiation toxicity in normal intestine. EXPERIMENTAL DESIGN: The effect of auranofin (10 mg/kg i.p.) on the radiation response of subcutaneous CT26 colon tumors and the normal gastrointestinal epithelium was determined using a mouse model of abdominal radiation. The effect of auranofin was also examined in a paired human colonic organoid system using malignant and nonmalignant tissues from the same patient. RESULTS: Both in the mouse model of intestinal injury and in the human nonmalignant colon organoid culture, auranofin pretreatment prevented radiation toxicity and improved survival with the activation of p53/p21-mediated reversible cell-cycle arrest. However, in a mouse model of abdominal tumor and in human malignant colonic organoids, auranofin inhibited malignant tissue growth with inhibition of proteosomal degradation, induction of endoplasmic reticulum stress/unfolded protein response, and apoptosis. CONCLUSIONS: Our data suggest that auranofin is a potential candidate to be considered as a combination therapy with radiation to improve therapeutic efficacy against abdominal malignancies.

Stressed Out - Therapeutic Implications of ER Stress Related Cancer Research.

The unfolded protein response (UPR) is an established and well-studied cellular response to the stress and serves to relieve the stress and reinstate cellular homeostasis. It occurs in the endoplasmic reticulum (ER), responsible of properly folding and processing of secretory and transmembrane proteins. It is extremely sensitive to alteration in homeostasis caused by various internal or external stressors which leads to accumulation of misfolded or unfolded proteins in the ER lumen. The UPR works by restoring protein homeostasis in the ER, either through the boosting of protein-folding and degradation capability or by assuaging the demands for such effects, and can cause the activation of cell death if unable to do so. Cancer cells have adapted to gain advantage from the UPR and keeping the cell away from apoptosis and promoting survival, including survival of the cancer stem cells and evading the immune system. Several components of the UPR are overexpressed in a malignant cell and are responsible for resistance from various chemotherapy options and radiotherapy, which are also responsible for causing ER stress and activating the UPR. In this review, we discuss the various ways in which UPR can aid different cancers to survive and evade therapy and highlight recent research, which exploits the UPR to confer sensitivity to these cancer cells against various drugs and radiation.