It has been reported that excessive inflammatory cytokines such as IL-1beta, IL-6 and TNF-alpha in the serum secreted from the tumor tissues are responsible for the development of weight loss up to 5% decrease within 6 months, also referred to as cachexia. Hyper-metabolism in skeletal muscles and adipose tissues is characterized by promoted beta-oxidation of free fatty lipids in mitochondria. Enhanced beta-oxidation causes accumulated ROS. In addition, the cachexia cancer cells lead to the activation of p38-MAPK signal pathway in skeletal muscle cells. I wonder whether metabolite-induced ROS directly activates p38-MAPK signaling cascade, and furthermore, other stress-response signal pathways are related or not in the cachexic pathophysiology.
Thank you for the detailed explanation!
CD44 variant-positive normal tissue and/or cancer stem-like cells tend to be resistant to be positive for phosphorylation of p38-MAPK under redox stress.
The IL-6 and/or TNF-alpha inhibitor has attracted attention as the treatment against auto-immune diseases including rheumatoid arthritis and SLE.
These medical agents are alredy used for patients with cachexia?
Interesting discussion!
I was wondering if exercise has the ability to reverse weight loss and muscle wasting (cachexia). If so, is it through the inhibition of p38-MAPK signaling cascade in skeletal muscle cells?
Thanks!
Hi Joshua, thanks for the reply. Do we have any scientific proof that exercise exacerbates cachexia?
Thanks!