Purpose Lung cancer is a leading cause of cancer deaths and efforts are underway to identify novel therapies to treat these tumors. Diacylglycerol kinase η (DGKη), an enzyme that phosphorylates diacylglycerol to form phosphatidic acid, has been shown to modulate MAPK signaling downstream of EGFR, which is an oncogenic driver in some lung cancers. Since mutations in EGFR and K-Ras are common in lung cancer, we hypothesized that limiting the function of DGKη would attenuate oncogenic properties of lung cancer cells. Methods We determined the expression levels of DGKη in a mouse models of mutant EGFR and K-Ras lung cancer and in human lung cancer cell lines with activating mutations in either EGFR or K-Ras. We also tested the effects of shRNA-mediated depletion of DGKη in lung cancer cells and tested if DGKη depletion augmented the effects of afatinib, a new generation EGFR inhibitor. Results DGKη was expressed in malignant epithelium from mice with mutant EGFR or K-Ras lung cancer. It was also expressed in human lung cancer cell lines with EGFR or K-Ras mutations. Depleting DGKη in lung cancer cell lines, harboring mutant EGFR, reduced their growth on plastic and in soft agar and also augmented the effects of afatinib, an EGFR inhibitor. DGKη depletion also reduced growth of one of two lung cancer cell lines that harbored mutant K-Ras. Conclusions Our data indicate that DGKη is a potential therapeutic target in lung cancers, especially those harboring EGFR mutations. Our findings warrant further studies to examine the effects of limiting its function in vivo.

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Background: Bronchoscopy is an aerosol-generating procedure and can place the health care providers at risk for exposure to viral pathogens. The pattern of aerosol generation during  different aspects of bronchoscopy are poorly understood. The goal of this study is to characterize the pattern of aerosol generation during flexible and rigid bronchoscopy performed under moderate sedation or general anesthesia (GA). The inhalable mass concentration of aerosol generated during the procedures was measured continuously. Methods: The aerosol concentration in the endoscopy room at baseline and while the procedures were performed was measured. Procedures included flexible bronchoscopies with moderate sedation, flexible bronchoscopies performed through endotracheal tube under GA and rigid bronchoscopies under GA. Changes from the baseline were measured continuously during the bronchoscopy. Results: Measurements obtained during the procedure were compared with the baseline reading. For flexible bronchoscopy under moderate sedation, the inhalable aerosol fraction was significantly higher (P=0.036) during atomization of lidocaine. For Flexible bronchoscopy through endotracheal tube, inhalable aerosol fraction was significantly higher (P<0.001) during intubation and extubation. For rigid bronchoscopy done under GA with jet ventilation, inhalable aerosol fraction was significantly higher during both the bronchoscopy (P=0.01) and recovery (P=0.012). Conclusion: Elevated levels of aerosol were generated during all aspects of bronchoscopy. However, atomization of lidocaine, intubation, extubation, and recovery generated the most aerosol.