Search

Introduction: Given that an incidental pulmonary nodule (IPN) on chest computed tomography (CT) may represent nascent lung cancer, timely follow-up imaging is critical to assess nodule growth and the need for tissue sampling. We previously reported our institution’s systematic process to identify and track patients with an IPN associated with improved CT on follow-up. We hypothesized that this improvement may have led to a higher frequency of early-stage lung cancer. To evaluate this, we performed a study to determine whether cases of early-stage lung cancer were more likely to have had our tracking system applied to suspicious findings. Methods: An observational study was performed by identifying cases of lung cancer that were detected as IPNs on chest CT scans performed at our institution, from 2006 to 2016. A total of 314 cases were dichotomized into early-stage (stage 1) or late-stage (stages II to IV) disease. A multivariant regression analysis with modeling was used to determine factors associated with a diagnosis of early-stage disease. Factors included the use of the tracking system and nodule registry. Results: The following factors were independently associated with early-stage lung cancer: index nodule diameter, (OR = 0.971, confidence interval [CI]: 0.948–0.995], p = 0.016), adenocarcinoma histology (OR = 2.930 [CI: 1.695–5.064], p = 0.0001) and use of tracker phrases on CT reports (OR = 1.939 [CI: 1.126–3.339], p = 0.016). Conclusions: The application of a patient tracking system and computerized lung nodule registry lead to an increased frequency in the diagnosis of stage 1 NSCLC from IPNs. This is a meaningful outcome for patients and should be adapted for IPN management.

Blood-feeding arthropods secrete potent salivary molecules, which include platelet aggregation inhibitors, vasodilators, and anticoagulants. Among these molecules, Alboserpin, the major salivary anticoagulant from the mosquito vector Aedes albopictus , is a specific inhibitor of the human coagulation factor Xa (FXa). In this study, we investigated the anti-inflammatory properties of Alboserpin, in vitro and in vivo. In vitro, Alboserpin inhibited FXa-induced protease-activated receptor (PAR)-1, PAR-2, PAR-3, VCAM, ICAM, and NF-κB gene expression in primary dermal microvascular endothelial cells. Alboserpin also prevented FXa-stimulated ERK1/2 gene expression and subsequent inflammatory cytokine release (MCP-1, TNF-α, IL-6, IL-8, IL-1β, IL-18). In vivo, Alboserpin reduced paw edema induced by FXa and subsequent release of inflammatory cytokines (CCL2, MCP-1, IL-1α, IL-6, IL-1β). Alboserpin also reduced FXa-induced endothelial permeability in vitro and in vivo. These findings show that Alboserpin is a potent anti-inflammatory molecule, in vivo and in vitro, and may play a significant role in blood feeding., (Copyright © 2022 The Authors.)

Phosphatidyl inositol (4,5)-bisphosphate (PI(4,5)P 2 ) plays several key roles in human biology and the lipid kinase that produces PI(4,5)P 2 , PIP5K, has been hypothesized to provide a potential therapeutic target of interest in the treatment of cancers. To better understand and explore the role of PIP5K in human cancers there remains an urgent need for potent and specific PIP5K inhibitor molecules. Following a high throughput screen of the AstraZeneca collection, a novel, moderately potent and selective inhibitor of PIP5K, 1, was discovered. Detailed exploration of the SAR for this novel scaffold resulted in the considerable optimization of both potency for PIP5K, and selectivity over the closely related kinase PI3Kα, as well as identifying several opportunities for the continued optimization of drug-like properties. As a result, several high quality in vitro tool compounds were identified (8, 20 and 25) that demonstrate the desired biochemical and cellular profiles required to aid better understanding of this complex area of biology., (Copyright © 2021 Elsevier Ltd. All rights reserved.)