The researchers, led by Zigang Dong, director of the university's Hormel Institute in Austin, Minn., have applied for a patent on one such treatment. The work will be published online July 10 in the journal Nature Structural & Molecular Biology.
A critical event in the development of melanoma and other human cancers is the inactivation of a gene known as "p16." Normally, p16 keeps cells from growing rapidly, a condition that sometimes leads to tumor formation. Working with mouse epidermis and cultured human melanoma and nonmelanoma cancer cells, the team found that p16 inactivates key enzymes - called JNK 1 and JNK 2 - in the process. The enzymes are normally activated by exposure to ultraviolet light. By shutting down the enzymes, p16 keeps them from activating a huge complex of proteins, which, when active, attaches to chromosomes and turns on many genes that promote cell growth.
The p16 gene works by producing a protein that attaches to the enzymes, preventing them from performing their function. When the researchers added the p16 protein to colonies of cancer cells in culture, it diminished the size of many colonies, wiping out some of them. It also decreased the total number of cancer cells.
The researchers have designed a very small protein that mimics the action of the natural p16 protein.
"We hope this [small protein] will have anti-cancer activity," said Dong. "We are testing it now." A patent application on the protein has been filed. Dong said he hopes to see clinical trials of this or similar treatments begin in a few years.
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X-ALD affects 16,000 patients in the United States. The disease causes the breakdown of myelin, a fatty substance that acts as an insulator around nerve fibers. Symptoms appear between four and 10 years of age, and can lead to nerve deterioration, loss of verbal communication, strength and coordination and, eventually, complete breakdown of bodily function.
"The results of this trial offer clinical support for treating the many young boys identified at high-risk for the disease," said Gary Goldstein, M.D., CEO of the Kennedy Krieger Institute. "This advance results from truly collaborative efforts between researchers in the medical community, parents and advocates for these patients."
There is still no cure for X-ALD, and treatment options are limited to hormone therapy and bone marrow transplants. While these transplants can provide important long-term benefits to boys with X-ALD in whom brain involvement is still in the early stages, the procedure carries a significant risk of mortality and morbidity, and is not effective when brain involvement is already severe.
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