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Experiments could lead to new treatments for neuroblastoma
Date:8/15/2008

GALVESTON, Texas Neuroblastoma is one of the most devastating diagnoses a child can receive. The cancer's victims average 2 years old when the disease is detected, most often by a parent feeling a lump in a child's abdomen. By then, the disease has often reached an advanced stage, and advanced neuroblastoma kills more than 50 percent of the children in whom it develops, despite aggressive treatment with surgery, chemotherapy and radiation.

Now, though, University of Texas Medical Branch at Galveston researchers believe they've found a critical weakness in the deadly cancer one that could lead to the development of a lifesaving therapy. In a paper published this week in the "Proceedings of the National Academy of Sciences," a team led by associate professor of surgery Dr. Dai H. Chung describes cell-culture and animal experiments that demonstrate how shutting down a single biochemical signaling connection dramatically suppresses neuroblastoma tumor formation and slows the cancer's spread.

Their investigation centered on an intercellular signaling molecule known as gastrin-releasing peptide, or GRP, and the receptor molecule with which it docks on the cell's surface. GRP activates the production of gastrin, a hormone that among other things controls the release of gastric acid in the stomach; GRP is also produced by neuroblastoma cells and acts to accelerate their proliferation, a discovery made earlier by the UTMB group.

"We had previously demonstrated that GRP stimulates the growth of this particular cancer," said Chung. "This time we wanted to demonstrate the opposite effects by targeting GRP receptors in neuroblastoma, to see if we could make the cancer regress."

To "target" GRP, the researchers took a line of aggressive human neuroblastoma cells and added short-hairpin RNAs, tiny bits of genetic material specifically designed to keep cells from making particular proteins in this case GRP receptor molecules. E
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Contact: Jim Kelly
jpkelly@utmb.edu
409-772-8791
University of Texas Medical Branch at Galveston
Source:Eurekalert

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