Non-canonical inflammasome activation that recognizes intracellular lipopolysaccharide (LPS) causes pyroptosis, the inflammatory death of innate immune cells. The role of pyroptosis in innate immune cells is to rapidly eliminate pathogen-infected cells and limit the replication niche in the host body. Whether this rapid cell elimination process of pyroptosis plays a role in elimination of cancer cells is largely unknown. Our earlier study demonstrated that a multi-functional secreted protein, secretoglobin (SCGB) 3A2, chaperones LPS to cytosol, and activates caspase-11 and the non-canonical inflammasome pathway, leading to pyroptosis. Here we show that SCGB3A2 exhibits marked anti-cancer activity against 5 out of 11 of human non-small cell lung cancer cell lines in mouse xenographs, while no effect was observed in 6 of 6 small cell lung cancer cell lines examined. All SCGB3A2-LPS-sensitive cells express syndecan 1 (SDC1), a SCGB3A2 cell surface receptor, and caspase-4 (CASP4), a critical component of the non-canonical inflammasome pathway. Two epithelial-derived colon cancer cell lines expressing SDC1 and CASP4 were also susceptible to SCGB3A2-LPS treatment. TCGA analysis revealed that lung adenocarcinoma patients with higher SCGB3A2 mRNA levels exhibited better survival. These data suggest that SCGB3A2 uses the machinery of pyroptosis for the elimination of human cancer cells via the non-canonical inflammasome pathway, and that SCGB3A2 may serve as a novel therapeutic to treat cancer, perhaps in combination with immuno and/or targeted therapies.
Background:Six risk factors for screw cutout after internal fixation of intertrochanteric fractures have been reported. The purpose of the present study was to evaluate and compare the impact of the 6 risk factors of screw cutout to clarify the most important one.Methods:We enrolled 8 consecutive patients who had screw cutout and 48 random control subjects after internal fixation of intertrochanteric fractures treated with proximal femoral nail antirotation systems at our institution. All of the patients were female. The group that had screw cutout and the control group were retrospectively evaluated and compared with respect to the OTA/AO classification, presence of a posterolateral fragment, types of reduction pattern on anteroposterior and lateral radiographic images, position of the screw, and the presence of a tip-apex distance (TAD) of ≥20 mm. The impact of each factor on screw cutout was assessed using backward stepwise multivariable logistic regression analysis with the Akaike information criterion. Risk stratification was assessed using classification and regression tree (CART) analysis.Results:Among 6 risk factors, only a TAD of ≥20 mm had a significant impact on screw cutout, with an adjusted odds ratio of 12.4 (95% confidence interval, 1.6 to 129.0; p = 0.019). CART analysis also demonstrated that a TAD of ≥20 mm was the most important risk stratification factor (p < 0.001).Conclusions:Among the 6 previously reported screw cutout-related factors, only a TAD of ≥20 mm was associated with screw cutout after internal fixation of intertrochanteric fractures with proximal femoral nail antirotation systems.Level of Evidence:Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.