Prevalence of Epidermal Growth Factor Receptor and Programmed Death Ligand 1 Testing in a Population-Based Lung Cancer Surgical Resection Cohort from 2018 to 2022.

Background: Biomarker-directed therapy requires biomarker testing. We assessed the patterns of epidermal growth factor receptor (EGFR) and programmed death ligand 1 (PDL1) testing in a non-small cell lung cancer (NSCLC) resection cohort. We hypothesized that testing would increase but be unevenly distributed across patient-, provider- and institution-level demographics.

Program-Based Lung Cancer Care: A Prospective Observational Tumor Registry Linkage Study.

Introduction: Low-dose computed tomography screening (LDCT) and lung nodule programs (LNP) promote early lung cancer detection, improve survival; Multidisciplinary Care Programs (MDC) promote guideline-concordant care. The impact of such program-based care on "real-world" lung cancer survival is unquantified. We evaluated outcomes of lung cancer care delivered through structured programs in a community health care system.

Incidentally Detected Lung Cancer in Persons Too Young or Too Old for Lung Cancer Screening in a Mississippi Delta Cohort.

Introduction: Lung cancer risk in screening age-ineligible persons with incidentally detected lung nodules is poorly characterized. We evaluated lung cancer risk in two age-ineligible Lung Nodule Program (LNP) cohorts.

Methods: Prospective observational study comparing 2-year cumulative lung cancer diagnosis risk, lung cancer characteristics, and overall survival between low-dose computed tomography (LDCT) screening participants aged 50 to 80 years and LNP participants aged 35 to younger than 50 years (young) and older than 80 years (elderly).

Two Interventions on Pathologic Nodal Staging in a Population-Based Lung Cancer Resection Cohort.

Background: Despite its prognostic importance, poor pathologic nodal staging of lung cancer prevails. We evaluated the impact of 2 interventions to improve pathologic nodal staging.

Methods: We implemented a lymph node specimen collection kit to improve intraoperative lymph node collection (surgical intervention) and a novel gross dissection method for intrapulmonary node retrieval (pathology intervention) in nonrandomized stepped-wedge fashion, involving 12 hospitals and 7 pathology groups.

Evaluation of Lung Cancer Risk Among Persons Undergoing Screening or Guideline-Concordant Monitoring of Lung Nodules in the Mississippi Delta.

Importance: Guideline-concordant management of lung nodules promotes early lung cancer diagnosis, but the lung cancer risk profile of persons with incidentally detected lung nodules differs from that of screening-eligible persons.

Objective: To compare lung cancer diagnosis hazard between participants receiving low-dose computed tomography screening (LDCT cohort) and those in a lung nodule program (LNP cohort).

Design, Setting, And Participants: This prospective cohort study included LDCT vs LNP enrollees from January 1, 2015, to December 31, 2021, who were seen in a community health care system.

Doxorubicin-Induced Fetal Mesangial Cell Death Occurs Independently of TRPC6 Channel Upregulation but Involves Mitochondrial Generation of Reactive Oxygen Species.

Doxorubicin (DOX), a category D pregnancy drug, is a chemotherapeutic agent that has been shown in animal studies to induce fetal toxicity, including renal abnormalities. Upregulation of the transient receptor potential cation (TRPC) 6 channel is involved in DOX-induced podocyte apoptosis. We have previously reported that TRPC6-mediated Ca signaling promotes neonatal glomerular mesangial cell (GMC) death.

Early onset of renal oxidative stress in small for gestational age newborn pigs.

Objective: Oxidative stress, a common feature in cardiovascular and renal disease is associated with the causes and consequences of fetal growth restriction. Hence, renal redox status is likely an early determinant of morbidity in small-for-gestational-age (SGA) infants. In this study, we examined renal oxidative stress in naturally-farrowed SGA newborn pigs.

γ-secretase inhibitor DAPT mitigates cisplatin-induced acute kidney injury by suppressing Notch1 signaling.

Organ toxicity, including kidney injury, limits the use of cisplatin for the treatment of multiple human cancers. Hence, interventions to alleviate cisplatin-induced nephropathy are of benefit to cancer patients. Recent studies have demonstrated that pharmacological inhibition of the Notch signaling pathway enhances cisplatin efficacy against several cancer cells.

TRPV4 channels contribute to renal myogenic autoregulation in neonatal pigs.

Myogenic response, a phenomenon in which resistance size arteries and arterioles swiftly constrict or dilate in response to an acute elevation or reduction, respectively, in intravascular pressure is a key component of renal autoregulation mechanisms. Although it is well established that the renal system is functionally immature in neonates, mechanisms that regulate neonatal renal blood flow (RBF) remain poorly understood. In this study, we investigated the hypothesis that members of the transient receptor potential vanilloid (TRPV) channels are molecular components of renal myogenic constriction in newborns.

Oxyradical stress increases the biosynthesis of 2-arachidonoylglycerol: involvement of NADPH oxidase.

NADPH oxidase (Nox)-derived oxyradicals contribute to atherosclerosis by oxidizing low-density lipoproteins (LDL), leading to their phagocytosis by vascular macrophages. Endocannabinoids, such as 2-arachidonoylglycerol (2-AG), might be an important link between oxidative stress and atherosclerosis. We hypothesized that 2-AG biosynthesis in macrophages is enhanced following ligation of oxidized LDL by scavenger receptors via a signal transduction pathway involving Nox-derived ROS that activates diacylglycerol lipase-β (DAGL-β), the 2-AG biosynthetic enzyme.

Oxyradical Stress, Endocannabinoids, and Atherosclerosis.

Atherosclerosis is responsible for most cardiovascular disease (CVD) and is caused by several factors including hypertension, hypercholesterolemia, and chronic inflammation. Oxidants and electrophiles have roles in the pathophysiology of atherosclerosis and the concentrations of these reactive molecules are an important factor in disease initiation and progression. Overactive NADPH oxidase (Nox) produces excess superoxide resulting in oxidized macromolecules, which is an important factor in atherogenesis.

Chemical Atherogenesis: Role of Endogenous and Exogenous Poisons in Disease Development.

Chemical atherogenesis is an emerging field that describes how environmental pollutants and endogenous toxins perturb critical pathways that regulate lipid metabolism and inflammation, thus injuring cells found within the vessel wall. Despite growing awareness of the role of environmental pollutants in the development of cardiovascular disease, the field of chemical atherogenesis can broadly include both exogenous and endogenous poisons and the study of molecular, biochemical, and cellular pathways that become dysregulated during atherosclerosis. This integrated approach is logical because exogenous and endogenous toxins often share the same mechanism of toxicity.

Organochlorine insecticides induce NADPH oxidase-dependent reactive oxygen species in human monocytic cells via phospholipase A2/arachidonic acid.

Bioaccumulative organohalogen chemicals, such as organochlorine (OC) insecticides, have been increasingly associated with disease etiology; however, the mechanistic link between chemical exposure and diseases, such as atherosclerosis, cancer, and diabetes, is complex and poorly defined. Systemic oxidative stress stemming from OC exposure might play a vital role in the development of these pathologies. Monocytes are important surveillance cells of the innate immune system that respond to extracellular signals possessing danger-associated molecular patterns by synthesizing oxyradicals, such as superoxide, for the purpose of combating infectious pathogens.

Identification of palmitoyl protein thioesterase 1 in human THP1 monocytes and macrophages and characterization of unique biochemical activities for this enzyme.

The profiles of serine hydrolases in human and mouse macrophages are similar yet different. For instance, human macrophages express high levels of carboxylesterase 1 (CES1), whereas mouse macrophages have minimal amounts of the orthologous murine CES1. On the other hand, macrophages from both species exhibit limited expression of the canonical 2-arachidonoylglycerol (2-AG) hydrolytic enzyme, MAGL.