Fate and Efficacy of Engineered Allogeneic Stem Cells Targeting Cell Death and Proliferation Pathways in Primary and Brain Metastatic Lung Cancer.

Primary and metastatic lung cancer is a leading cause of cancer-related death and novel therapies are urgently needed. Epidermal growth factor receptor (EGFR) and death receptor (DR) 4/5 are both highly expressed in primary and metastatic non-small cell lung cancer (NSCLC); however, targeting these receptors individually has demonstrated limited therapeutic benefit in patients. In this study, we created and characterized diagnostic and therapeutic stem cells (SC), expressing EGFR-targeted nanobody (EV) fused to the extracellular domain of death DR4/5 ligand (DRL) (EVDRL) that simultaneously targets EGFR and DR4/5, in primary and metastatic NSCLC tumor models. We show that EVDRL targets both cell surface receptors, and induces caspase-mediated apoptosis in a broad spectrum of NSCLC cell lines. Utilizing real-time dual imaging and correlative immunohistochemistry, we show that allogeneic SCs home to tumors and when engineered to express EVDRL, alleviate tumor burden and significantly increase survival in primary and brain metastatic NSCLC. This study reports mechanistic insights into simultaneous targeting of EGFR- and DR4/5 in lung tumors and presents a promising approach for translation into the clinical setting.

Dexamethasone versus ondansetron in combination with dexamethasone for the prophylaxis of postoperative vomiting in pediatric outpatients: a double-blind, randomized, placebo-controlled clinical trial.

OBJECTIVES: To determine the frequency of postoperative vomiting (POV) in children submitted to outpatient surgery and to compare the efficacy of antiemetic drugs in preventing this complication. BACKGROUND: Nausea and vomiting are common in the immediate postoperative period following anesthetic and surgical procedures. Compared to adults, pediatric patients are more likely to develop postoperative nausea and vomiting, the incidence of which ranges from 8.9% to 42%. METHODS: This double-blind, randomized, placebo-controlled clinical trial included 129 children. The participants were randomized into three prophylactic treatment groups: dexamethasone (n = 43), ondansetron in combination with dexamethasone (n = 44), and placebo (n = 42). The variables studied were the frequency of POV and the incidence of vomiting after the patient had been discharged from hospital, the need for antiemetic rescue therapy in the postanesthesia care unit (PACU), need for hospitalization, and the time the patient remained in the PACU. A significance level of 5% was adopted. RESULTS: Postoperative vomiting occurred in 12.4% of the children, with no statistically significant difference between the groups: 6.8% in the group receiving ondansetron combined with dexamethasone, 14.3% in the placebo group, and 14% in the group that received dexamethasone alone (P = 0.47). Furthermore, no significant difference was found between the groups with respect to the time the children remained in the PACU, and only five patients reported having vomited following discharge from hospital. CONCLUSIONS: The prophylactic use of antiemetic drugs failed to reduce the incidence of POV in pediatric outpatient surgery with a low emetic potential; therefore, routine prophylaxis may be unnecessary.