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Study appears to show why muscle decays mysteriously in cancer, AIDS, other illnesses

CHAPEL HILL - University of North Carolina at Chapel Hill scientists believe they have discovered a major reason why muscles often decay in patients with cancer, AIDS, late-stage heart disease, severe burns and numerous chronic diseases. Their research focuses on cachexia, an important syndrome they say doctors know well but which is largely unfamiliar to lay people, and could lead to an effective treatment for the condition.

Cachexia, which kills an estimated one third of cancer patients, results from activation of a factor known as NF-kappa B, the new experiments show. NF-kappa B, a natural substance that attaches to DNA inside cell nuclei and turns genes on and off like a switch, prevents expression of a key regulatory protein called MyoD from replenishing muscle tissue as it does in healthy people.

A report on the work appears in the Sept. 29 issue of Science. Authors, all of the UNC-CH School of Medicine's Lineberger Comprehensive Cancer Center, are postdoctoral fellows Denis C. Guttridge, Marty W. Mayo and Cun Yu Wang, as well as Dr. Albert S. Baldwin Jr., a biology professor. Graduate student Lee V. Madrid of the Curriculum in Genetics and Microbiology also helped with the research.

"Cancer cachexia, which causes patients to waste away, literally, has been documented for at least 100 years, but it wasn't until about 20 years ago that researchers discovered a cytokine protein called tumor necrosis factor and that the factor could elicit cachexia," Guttridge said. "What we have done is to identify a key part of what's happening mechanistically inside muscle cells to cause cachexia."

The UNC-CH experiments, which involved both cultured mouse muscle cells and muscle in live mice, clearly implicated NF-kappa B as a destructive link between tumor necrosis factor and MyoD, he said. When NF-kappa B is either absent or inactivated, muscle cells containing MyoD develop and grow normally.

"When you see cancer patients becoming very frail and
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Contact: David Williamson
rdtokids@email.unc.edu
919-962-8596
University of North Carolina at Chapel Hill
27-Sep-2000


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