Research Round-Up

NEW DRUG CUTS RISK OF GRAFT-VS.-HOST DISEASE FOLLOWING BONE MARROW TRANSPLANT IN HALF

Sung Choi, MD and Pavan Reddy, MD
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A new class of drugs reduced the risk of patients contracting a serious and often deadly side effect of lifesaving bone marrow transplant treatments, according to a study from researchers at the University of Michigan Comprehensive Cancer Center.

The study, the first to test this treatment in people, combined the drug vorinostat with standard medications given after transplant, resulting in 21 percent of patients developing graft-vs.-host disease compared to 42 percent of patients who typically develop this condition with standard medications alone.

"Graft-vs.-host disease is the most serious complication from transplant that limits our ability to offer it more broadly. Current prevention strategies have remained mostly unchanged over the past 20 years. This study has us cautiously excited that there may be a potential new way to prevent this condition," says lead study author Sung Choi, M.D., assistant professor of pediatrics at the U-M Medical School.

Vorinostat is currently approved by the U.S. Food and Drug Administration to treat certain types of cancer. But U-M researchers, led by senior study author Pavan Reddy, M.D., found in laboratory studies that the drug had anti-inflammatory effects as well—which they hypothesized could be useful in preventing graft-vs.-host disease, a condition in which the new donor cells begin attacking other cells in the patient's body.

The first 47 participants were older adults who were undergoing a reduced-intensity bone marrow transplant with cells donated from a relative. Patients received standard medication used after a transplant to prevent graft-vs.-host disease. They also received vorinostat, which is given as a pill taken by mouth.

The researchers found vorinostat was safe and tolerable to give to this vulnerable population, with manageable side effects. In addition, rates of patient death and cancer relapse among the study participants were similar to historical averages.

CAPTURING CIRCULATING CANCER CELLS COULD PROVIDE INSIGHTS INTO HOW CANCER SPREADS

cells on a block M
This false-color microscopic image shows cancer cells selectively adhering to patterned nanorough letters (UM) on a glass surface.

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A glass plate with a nanoscale roughness could be a simple way for scientists to capture and study the circulating tumor cells that carry cancer around the body through the bloodstream.

Engineering and medical researchers at the University of Michigan have devised such a set-up, which they say takes advantage of cancer cells' stronger drive to settle and bind compared with normal blood cells.

Circulating tumor cells are believed to contribute to cancer metastasis, the process of the disease spreading from its original site to distant tissues. Blood tests that count these cells can help doctors predict how long a patient with widespread cancer will live.

As important as the castaway cells are, scientists don't know a lot about them. They're rare, at about one per billion blood cells. And they are not all identical, even if they come from the same tumor. Existing tools for isolating them only catch certain types of cells -- those that express specific surface proteins or are larger than normal blood cells.

"Our system can capture the majority of circulating tumor cells regardless of their surface proteins or their physical sizes, and this could include cancer progenitor or initiating cells," said Jianping Fu, assistant professor of mechanical engineering and biomedical engineering and a senior author of a paper on the technique published online in ACS Nano.

Fu and his engineering colleagues teamed up with U-M cancer researcher and breast cancer clinician Sofia Merajver, M.D., Ph.D., and her team. This multidisciplinary group believes that while the device could one day improve cancer diagnosis and prognosis, its first uses would be for researchers to isolate live circulating tumor cells from blood specimens and study their biological and physical properties.

"Understanding the physical behavior and nature of these circulating tumor cells will certainly help us understand better one of the most difficult questions in cancer biology -- the metastatic cascade, that is, how the disease spreads," Fu said. "Our system could provide an efficient and powerful way to capture the live circulating tumor cells and use them as a surrogate to study the metastatic process."

This works was done in the laboratory. More research is needed before the technique can be offered to patients.

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Thrive Issue: 
Spring, 2013