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Neurotransmitters signal aggressive cancer, offer potential for early diagnosis

Nerves talk to each other using chemicals called neurotransmitters. One of those "communication chemicals," aptly named GABA (gamma amino butyric acid), shows up in unusually high amounts in some aggressive tumors, according to a new study from Washington University School of Medicine in St. Louis.

The researchers investigated metastatic neuroendocrine tumors, which include aggressive types of lung, thyroid, and prostate cancers that spread to other parts of the body. Their study will appear in the July 12 issue of the Proceedings of the National Academy of Sciences and is available online after July 4.

"GABA appears to be an indicator of a bad prognosis for these cancers," says Jeffrey I. Gordon, M.D., director of the Center for Genome Sciences at Washington University. "But there's hope in our ability to identify substances, like GABA, that are associated with metastatic tumors. Usually these tumors are diagnosed only after they have spread to other parts of the body, but now we have the potential to recognize them before they metastasize."

Elevated amounts of GABA were discovered in an analysis of aggressive neuroendocrine prostate tumors in genetically engineered mice. Along with GABA, two other substances were seen, one a related neurotransmitter and the other a plant growth hormone with an unknown function in animals. Furthermore, the researchers found that the tumors made GABA using a different set of biochemical reactions than normal. Key enzymes involved in the production of these compounds were switched on in poor prognosis malignant metastatic tumors.

"The mouse model was an important beginning point for our investigation," says the study's lead author Joseph E. Ippolito, a graduate research assistant in the University's NIH-supported Medical Scientist Training Program. "We took information about what genes were expressed in the mouse tumors, made computer-assisted predictions about what type of metabolism was going on in th
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Source:Washington University School of Medicine


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