Removing deadly brain tumors diffuses a bomb but leaves a minefield because the "normal" brain tissue remains riddled with migrating tumor cells. New research shows that these cells can generate new tumors and that the drug Taxol, an experimental treatment for brain cancer, speeds the movement of brain tumor cells.
The American Cancer Society estimates that primary brain tumors will appear in 17,200 Americans in 1995 and kill 13,300. The most common primary brain tumor of middle-aged adults is the malignant glioma, which usually kills patients within two years after diagnosis.
Although glioma cells do not metastasize to other parts of the body, they wander through the brain, causing death from generalized brain dysfunction. "By the time the tumor is found, the cat is out of the bag," said Daniel L. Silbergeld, M.D., assistant professor of neurological surgery and of anatomy and neurobiology.
Silbergeld has devised ways to monitor the amoeba-like cells as they creep over the surfaces of plastic dishes. He was surprised to find that the cells traveled 3 centimeters in four days --600 times their length. The most active came from patients with the most malignant brain tumors. "This supports the idea that the degree of malignancy of a brain tumor relates to the ability of its cells to migrate into other parts of the brain," Silbergeld said.
Silbergeld and his team (Michael Chicoine, M.D., and research technician Cynthia Madsen) knew that the anti-cancer drug Taxol "locks up" the cellular skeleton, which assembles and disassembles as a cell moves. "We thought that giving Taxol to the cells would prevent them from moving and present a double whammy to these tumors," he said.
Just the opposite happened. Although Taxol killed many of the cultured glioma cells, it made the survivors migrate faster than ever, in a dose-dependent fashion.
Taxol is being given to brain tumor patients in Phase II clinical trials. "But our findings raise a cautionary note," Silbergeld said. "We may be making brain tumor cells more invasive. Taxol may also affect the migration of tumor cells in patients with ovarian and breast tumors."
Silbergeld's team also has implanted either rat brain tumor cells or brain tumor cells that had migrated from the tumor into the brains of healthy rats. Both formed new tumors at the same rate.
Silbergeld said he believes investigators should shift their focus away from visible tumors. "Because surgery alone will not cure these tumors, we need to pay more attention to the migrating cells," he said. "By exploiting differences between the invasive cells and the cells in the tumor, we may be able to devise better therapies."
These studies were supported by grants from the National Institutes of Health and Washington University's McDonnell Center for Molecular and Cellular Biology. They were published in the April issues of the Journal of Neurosurgery and AntiCancer Drugs.
-- Linda Sage
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