- The Washington Times - Friday, July 19, 2002

University of Florida researchers say they have found the first evidence that the most common type of brain tumors that strike adults are derived from abnormal stem cells in the brain.

The researchers say their findings could lead to new therapies that would be based on rehabilitating the abnormal stem cells, rather than trying to kill the tumor cells with radiation or chemotherapy.

"This is incredibly exciting research, which suggests a novel form of adjuvant therapy for patients with glioblastoma tumors [a particularly rapidly growing, aggressive form of adult brain tumor] for which curative therapy is essentially nonexistent," said Dr. Stratford May Jr., program director for the university's Shands Cancer Center in Gainesville.

The discovery by the research team, which included neuroscientist Dennis Steindler of the Shands Center, is based on extensive laboratory studies of brain cells from malignant gliomas, which represent about half of the 17,000 brain tumors diagnosed yearly in the United States. The brain cells used were from tumors surgically removed from human patients and then cultured under conditions that allowed researchers to isolate the stem cells.

"The UF investigators have found that glioblastoma tumor cells [a type of malignant glioma] derived from brain tumors of patients can maintain their stem-cell properties and may be induced to differentiate [mature] at least in the test tube," Dr. May said.

"This suggests that under appropriate therapeutic conditions, any brain tumor cells lurking after surgery and radiation therapy could be induced to turn into normal cells if the right conditions were identified and could be administered," he explained.

Stem cells, also known as progenitor cells, are the building blocks for all tissues. They can develop into bone, brain, muscles, skin, or any other organs.

The research appears in the July issue of the international journal, GLIA. Other authors of the paper were UF neuroscientists, Tanya Ignatova and Valery Kukekov.

In an interview yesterday, Mr. Steindler said it appears glioma tumor formation occurs when stem cells, originating in a particular part of the brain, begin to continually divide and regenerate but then "go too far" in the process of reproduction.

"Our findings suggest that the stem-cell population living in the brain are there to repair [damage to the brain] but because they proliferate, they can be targets of environmental or genetic mutations," Mr. Steindler said.

He said there has been speculation in recent years that brain tumors were linked to brain-stem cells. "We believe we have the first evidence this is true, and that it starts with stem cells that may have been produced in the region we call the brain marrow, near the brain's central core and the fluid-filled ventricles," he said.

His research colleagues said in a statement that when they grew the surgically removed glioma cells in culture, they saw cells that behaved like stem cells but displayed abnormal growth. Using an analytical technique developed by Miss Kukekov, they found that the stem cells and their progeny also contained genes different from those found in normal brain tissue.

Mr. Steindler said the researchers concluded the errant stem cells are the "culprit," not innocent bystanders, in brain tumor formation.

He said the researchers believe there could be a link between some types of brain injuries that actually precipitate brain marrow stem cells to move toward the problem area in a bid to repair it. "But while doing so, because these cells have to repopulate themselves to carry out the healing mission, [they] may go too far and produce tumors," Mr. Steindler said.

This procedure, he said, explains why malignant glioma cells are "almost impossible" to kill with radiation or drugs. "If we're dealing with abnormal brain marrow stem cells the stem cells are in the mode of trying to build and are highly resistant to standard cancer therapies," he explained.

Before any of this can be useful to humans with brain tumors, the UF scientists will be testing their findings on animals.

Asked if the UF findings could prove to be a breakthrough in brain cancer treatment, Mr. Steindler said, "In this new world of regenerative medicine, I think the answer is yes for the short run, the findings will make neuro-oncologists pay attention to our new ideas."

Key goals in follow-up studies will be to characterize genes involved in gliomas and to determine how they are turned on and off. The ultimate goal, Mr. Steindler said, is to make brain tumors "not terminal."

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