American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Sep 2014
HOIL-1L Functions as the PKCζ Ubiquitin Ligase to Promote Lung Tumor Growth.
Protein kinase C zeta (PKCζ) has been reported to act as a tumor suppressor. Deletion of PKCζ in experimental cancer models has been shown to increase tumor growth. However, the mechanisms of PKCζ down-regulation in cancerous cells have not been previously described. ⋯ These data provide first evidence of a mechanism of cancer cell adaptation to hypoxia where HIFs regulate HOIL-1L, which targets PKCζ for degradation to promote tumor survival. We provided a proof of concept that silencing of HOIL-1L impairs lung tumor growth and that HOIL-1L expression predicts survival rate in cancer patients suggesting that HOIL-1L is an attractive target for cancer therapy.
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Am. J. Respir. Crit. Care Med. · Sep 2014
Randomized Controlled Trial Multicenter Study Comparative StudyA Functional Synonymous Coding Variant in the IL1RN Gene Associates with Survival in Septic Shock.
Death from infection is a highly heritable trait, yet there are few genetic variants with known mechanism influencing survival during septic shock. ⋯ In European ancestry subjects, the IL1RN variant rs315952C is preferentially transcribed and associated with increased evoked plasma IL1RA and with improved survival from septic shock. It may be that genetically determined IL1RA levels influence survival from septic shock.
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Am. J. Respir. Crit. Care Med. · Sep 2014
Controlled Clinical TrialEpithelial Interleukin-25 is a Key Mediator in Th2-high, Corticosteroid-responsive Asthma.
Activation of type 2 cytokine pathways plays a central role in a large subset of subjects with asthma. Th2-high and Th2-low asthma have distinct clinical, pathologic, and molecular phenotypes and respond differently to therapy. The factors that initiate type 2 responses in some subjects with asthma are unknown. ⋯ IL-25 measurements identify two subsets of subjects with distinct asthma phenotypes and different responses to ICS. Because IL-25 has a major role in triggering type 2 responses, bronchial epithelial IL-25 expression is likely a key determinant of type 2 response activation in asthma. Plasma IL-25 level reflects airway IL-25/type 2 response activation and may be useful for predicting responses to asthma therapy.
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Am. J. Respir. Crit. Care Med. · Sep 2014
Comment Letter Case ReportsIn-Flight Pneumothorax: Diagnosis May Be Missed because of Symptom Delay.