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Zinc Overload Leading To Cachexia

1 year ago

5093  0
Posted on Jun 10, 2018, 5 p.m.

One third of all cancer deaths are estimated not to be caused by the cancers itself but by cachexia, which is a debilitating muscle wasting syndrome that affects 80% of advanced cancer patients, as published in Nature Medicine.


Cachexia has been linked to reduced tolerance for cancer therapies, accelerated death, and in general poor quality of life, for which there is no cure or effective treatments for and the cause is of it is still largely unknown. Columbia University researchers suggest that overload of zinc in patient muscles may be responsible for cachexia.

Cachexia occurs in various forms of cancer including lung, pancreatic, head, neck, and gastrointestinal cancers. Cachexia is not understood very well for various reasons such as in part due to limited funding for research in the area, difficulty developing accurate model animals, and lack of reliable biomarkers to help diagnose cachexia early and monitor progression during cancer treatment.


Cachexia being just a nutritional problem caused by loss of appetite stemming from cancer and/or treatments is a common misconception. Cachexia patients are typically given appetite stimulants which are only a temporary remedy as cachexia can’t be reversed. As cachexia continues to break down muscles patients become too weak to tolerate standard doses of cancer therapies and treatments must be scaled back. Patients can die from respiratory or heart failure if muscles of the diaphragm and heart become weakened. Much more needs to be learned about this condition’s underlying causes and molecular mechanisms associated with it to find ways to treat the syndrome.


Muscles of model mice were examined to see if differences could be found compared to normal muscles. Analysis revealed increased activity of ZIP14 proteins which are typically expressed in liver cells to facilitate metal transport, but was found to be abnormally expressed in the model cancer mice muscles. High levels of ZIP14 in samples of muscle tissue from cachexia cancer patients suggest a link between cachexia and ZIP14 in humans.


Excessive zinc uptake in muscles has been found to lead to muscle wasting in cancer, by breaking down mature muscle cells and preventing stem cells from making new muscle fibers.  ZIP14 pumping more zinc into muscles in cachexia was traced to systemic effects of cancer; TNF-alpha and TGF-beta associated with advanced cancer increases ZIP14 expression in muscles.


Zinc and ZIP14 discovered associations with cachexia may lead to methods to reduce cachexia impact on patients. Reducing ZIP14 in model animal muscle cells reduced cachexia, suggesting that drugs targeting ZIP14 could improve quality of life and improve cancer survival rates.


Zinc is critical to maintaining many bodily functions, but excess zinc is not a good thing, model animals with tumors fed excess zinc were observed to have accelerated weight loss and muscle wasting.


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