Muscle inflammation is regulated by NF-κB from multiple cells to control distinct states of wasting in cancer cachexia.

Although cancer cachexia is classically characterized as a systemic inflammatory disorder, emerging evidence indicates that weight loss also associates with local tissue inflammation. We queried the regulation of this inflammation and its causality to cachexia by exploring skeletal muscle, whose atrophy strongly associates with poor outcomes. Using multiple mouse models and patient samples, we show that cachectic muscle is marked by enhanced innate immunity.

Cellular and Molecular Mechanisms of MEK1 Inhibitor-Induced Cardiotoxicity.

Background: Trametinib is a MEK1 (mitogen-activated extracellular signal-related kinase kinase 1) inhibitor used in the treatment of BRAF (rapid accelerated fibrosarcoma B-type)-mutated metastatic melanoma. Roughly 11% of patients develop cardiomyopathy following long-term trametinib exposure. Although described clinically, the molecular landscape of trametinib cardiotoxicity has not been characterized.

Pushing boundaries of co-design by going online: Lessons learned and reflections from three perspectives.

The global COVID-19 pandemic made significant changes to our day-to-day lives, which impacted how we conduct research and design - including co-design. In this article, we present case studies from three different co-design groups that pushed the boundaries of traditional co-design, and conducted multiple co-design sessions (more than 150 total) over the last year and a half. The case studies for each team include: the transition to online co-design; the pros and cons of logistics and design tools utilized during the co-design sessions; and the advances, challenges, and surprises.

Application of Pharmacokinetic Prediction Platforms in the Design of Optimized Anti-Cancer Drugs.

Cancer is the second most common cause of death in the United States, accounting for 602,350 deaths in 2020. Cancer-related death rates have declined by 27% over the past two decades, partially due to the identification of novel anti-cancer drugs. Despite improvements in cancer treatment, newly approved oncology drugs are associated with increased toxicity risk.