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Michael Retsky, PhD (right), and Romano Demicheli, MD, PhD

Breast cancer, angiogenesis and the mammography paradox
Michael Retsky, PhD, of Children's Hospital Boston's Vascular Biology Program, is amassing indirect evidence that surgery for breast cancer can encourage early relapse in younger women. In their latest analysis, he and collaborator Romano Demicheli, MD, PhD, who lives in Milan, closely examined data from nearly 1,200 women who had a mastectomy but no other treatment for breast cancer. They found that relapses peaked eight to 10 months after surgery among premenopausal women with cancers that had spread to the lymph nodes. These early relapses, they theorize, resulted from the mastectomy, whereas later relapses were part of the cancer's natural course. Older women didn't show the early relapse peak.

So how could this happen? Retsky proposes that surgery triggers blood vessel formation (angiogenesis) in younger women, fueling the growth of microscopic, formerly dormant metastases (secondary tumors formed from cells that have spread from the original, or primary, tumor). The Folkman Lab has shown that primary tumors can secrete angiogenesis inhibitors, which naturally inhibit the growth of metastases, so surgically removing the primary tumor might eliminate natural checks on cancer relapse. Alternatively, surgery might spur release of angiogenesis promoters through a wound-healing mechanism.

Either way, Retsky believes that surgery-induced angiogenesis explains the "mammography paradox"’Äîthe puzzling link between breast cancer screenings in women aged 40 to 49 and a short-term increase in breast cancer deaths. The idea that surgeries following positive mammograms might accelerate cancer has rekindled debate over whether women in their 40s should be screened.

To review the analysis, published in the October 11 Breast Cancer Research, visit http://breast-cancer-research.com/content/6/6/R689.

 

Larry Benowitz, PhD

Making nerve cells regenerate
Advancing a decades-old quest, researchers led by Larry Benowitz, PhD, director of Children's Laboratories for Neuroscience Research, and Dietmar Fischer, PhD, have achieved some of the most extensive nerve regeneration ever seen in the central nervous system, where damaged nerve fibers normally can't regrow.

Over the past 15 years, researchers have found and blocked various inhibitors of nerve growth, but have gotten only modest regeneration. Benowitz reasoned that simply blocking inhibition is like trying to drive a car by taking your foot off the brake. "Our idea was to step on the gas as well’Äîto activate the growth state," he says.

Working with rats' optic nerves, which connect the retina with the brain's visual centers, Benowitz and Fischer used a two-pronged strategy. To activate growth, they stimulated immune cells known as macrophages to release growth factors. Next, they blocked most known growth inhibitors by inactivating the enzyme RhoA, at which multiple inhibitory signals converge. Nerve-fiber growth was dramatic, and the accompanying pattern of gene activity resembled that seen in the peripheral nervous system, where nerves regenerate naturally.

This strategy, described in the October 6 Journal of Neuroscience, won't cure blindness, but could potentially lead to sight-saving treatments when optic nerves are injured by trauma or tumors. Benowitz's team is now applying their techniques to nerves damaged by stroke and spinal cord injury.