Early Neutrophilia Marked by Aerobic Glycolysis Sustains Host Metabolism and Delays Cancer Cachexia

An elevated neutrophil–lymphocyte ratio negatively predicts the outcome of patients with cancer and is associated with cachexia, the terminal wasting syndrome. Here, using murine model systems of colorectal and pancreatic cancer we show that neutrophilia in the circulation and multiple organs, accompanied by extramedullary hematopoiesis, is an early event during cancer progression. Transcriptomic and metabolic assessment reveals that neutrophils in tumor-bearing animals utilize aerobic glycolysis, similar to cancer cells. Although pharmacological inhibition of aerobic glycolysis slows down tumor growth in C26 tumor-bearing mice, it precipitates cachexia, thereby shortening the overall survival. This negative effect may be explained by our observation that acute depletion of neutrophils in pre-cachectic mice impairs systemic glucose homeostasis secondary to altered hepatic lipid processing. Thus, changes in neutrophil number, distribution, and metabolism play an adaptive role in host metabolic homeostasis during cancer progression. Our findings provide insight into early events during cancer progression to cachexia, with implications for therapy

Analytics on farm dust extract for development of novel strategies to prevent asthma and allergic disease.

Therapeutics that are composed of highly heterogeneous, complex mixtures of biomolecular constituents, such as heparin and other botanicals drugs, where the active ingredient(s) are unknown or are challenging to define, pose a significant challenge to the FDA and EMA. Variation, which may arise during sourcing/cultivation of raw material or during production, can impact the therapeutic efficacy and safety of these therapeutic compounds. Recently, there has been an upsurge in interest in medicines that are derived from plants, microbes, and even traditional Chinese medicines (TCM). Inevitably, many such medicines will contain active ingredients which may be hard to unequivocally define and may challenge the delivery of products with robust safety and efficacy profiles. Consequently, there is a critical and timely need to define guidelines for approaching the development of therapies that are comprised of a complex mixture of molecular constituents. Considering a case study focused on developing farm dust extract-derived therapeutics to prevent atopy and asthma, we outline a conceptual framework to support the development of therapeutics composed of complex mixtures