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Single Protein May I.D. Aggressive Cancers
The most aggressive breast cancers may be detected by the levels of a single protein called stathmin, according to a new study led by Ramon Parsons, M.D., Ph.D., the Avon Foundation Professor of Pathology and Medicine, and Åke Borg of Sweden’s Lund University.
   In a retrospective analysis of samples from tumor banks, the researchers found that survival after diagnosis for breast cancer declines 8 percent to 16 percent for every one point increase in stathmin activity, which is scored on a scale from 0 to 12.
   Stathmin predicts survival, the researchers found, because it mirrors the activity of an entire molecular pathway inside cancer cells. When active, the PI3K/PTEN pathway promotes tumors in model systems. But its prognostic significance in human cancers had been unclear because previous assays could not detect all defects in the pathway.
   The new study identified a group of 246 genes that form a genetic microarray signature that detects aberrant PI3K/PTEN pathway activity. Breast, prostate, and bladder cancers exhibiting this signature had very poor prognosis, confirming the PI3K/PTEN pathway has a major impact on patients.
   “Patients with these types of aggressive tumors have few good treatment options and there is a real need for effective drugs,” says the study’s first author, Lao Saal, P&S’09. “The good news is that inhibiting the PI3K/PTEN pathway has enormous potential for improving survival and there are many attractive therapeutic targets in the pathway that may be exploited.”
   Because microarrays are expensive and hard to use in clinical settings, the researchers also looked for a simpler way to detect PI3K/PTEN defects. Simple immunodetection of stathmin proved an accurate surrogate for the full signature and may evolve into a clinically useful diagnostic test.
The research was supported, in part, by the NIH and the Avon Foundation.

Neuronal Competition Leads to More Psychiatric Disorders
Children born with an uncommon form of a certain brain protein are approximately
50 percent less likely to develop obsessive-compulsive disorder, depression and other psychiatric diseases during childhood.
   A new study by CUMC researchers now shows why this form of brain-derived neurotrophic factor (BDNF) may be so protective.
   Led by Joseph Gogos, M.D., Ph.D., assistant professor of physiology and cellular biophysics and in neuroscience, the study found that the “Met” form of BDNF prevents inactive neurons from withering away during brain development. BDNFmet – in which a methionine amino acid replaces the more common valine at position 66 in the protein – is present in about 10 percent of the population.
   The study focused on the olfactory bulb. The advantage of this brain region is that during the initial wiring of the sense of smell, thousands of neurons compete against each other for access to a few hundred cells. Active neurons have the advantage in this competitive playing field.
   BDNFmet reduces this competition and lets more inactive neurons gain access to the cells in the olfactory bulb, the researchers found.
   Psychiatric disorders in children may stem from an excessive loss of compromised neurons during competition in other parts of the brain. Dr. Gogos says that one way BDNFmet may protect against these disorders is by allowing more neurons to survive the competition.
The work was supported by the NIH, a Burroughs Wellcome Fund Career Award in the Biomedical Sciences, the Whitehall Foundation and NARSAD: The Mental Health Research Association.