"These compounds work against neuroblastoma and other cancers because they trigger cells to differentiate (form specialized cells) and stop dividing," he said. "But we observed that when the compounds are applied to medulloblastoma tumors, a large percentage of cancer cells actually die."
Retinoids are molecules naturally produced by the human body, where they play a critical role in normal development by triggering primitive cells to become specialized cells characteristic of a particular tissue, such as nerve cells in the brain. Scientists also have created synthetic retinoids, which have proved to be effective against some tumors because they drive cancer cells from their relatively primitive, undifferentiated state into specialized cells that cease to divide.
Hallahan and colleagues examined the effect of three retinoids on medulloblastoma tumor specimens obtained from surgeries.
"Thanks to our colleagues at Children's Hospital and Regional Medical Center in Seattle we were able to start our experiments right in the operating room by getting surgical sections that we could immediately put into culture medium," James Olson said. "This was a critical step because it was uncertain whether the available medulloblastoma cell lines (cells previously extracted from tumors and grown indefinitely in the laboratory) would accurately reflect the disease."
The experiment led to a surprising result, Hallahan said. "We began by looking for signs of differentiation, which is what we expected based on how the compounds affect neuroblastomas," he said. "About 5 to 10 percent of the medulloblastoma cells did differentiate. But what was immediately obvious to us was that there was a huge wave of cell death."
The researchers also found that mice transplanted with medulloblastoma tumors that were treated with retinoids developed tumors that were about a third of the size as those that grew on untreated mice.
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Contact: Susan Edmonds
sedmonds@fhcrc.org
206-667-2896
Fred Hutchinson Cancer Research Center
4-Aug-2003