Results of Johns Hopkins animal studies show that a natural shark substance nearly stops the growth of new blood vessels that nourish solid brain tumors.
The results suggest that the substance, squalamine, named for the shark genus Squalus, may find a role with chemotherapy, radiation and surgery in treating brain cancer and other solid tumors in people, say scientists from Hopkins and Magainin Pharmaceuticals, which processes squalamine and funded the studies.
Hopkins scientists added squalamine, a hormone-like chemical concentrated in the liver of the dogfish shark, and a growth factor to lab dishes containing central nervous system blood vessel cells from cows and squalamine alone to lab dishes containing human, rabbit or rat solid brain tumor cells. The blood vessel cells' rate of growth fell by up to 83 percent after two days, while the tumor cells treated with squalamine were unaffected. Results of a second study showed that time-release capsules containing squalamine slowed the growth of new blood vessels caused by tumors in rabbits' eyes by up to 43 percent after three weeks.
The studies are to be presented today at the American Association of Neurological Surgeons' annual meeting in Minneapolis, Minn.
Uncontrolled growth of blood vessels fuels the runaway cell growth of malignant tumors. Other investigators also are exploring natural shark substances for use against human diseases, but this is believed to be the first evidence that squalamine may work against brain cancer. Squalus sharks' livers produce an oil used in manufacturing drugs, and small amounts of squalamine are found in shark cartilage.
Squalamine dramatically slowed blood vessel cell growth without damaging healthy cells, according to Henry Brem, M.D., co-author of the studies and director of neurosurgical oncology at Hopkins and Allen K. Sills, M.D., lead author and a Hopkins neurosurgery resident.
"We're encouraged by these initial findings," says Brem, who successfully uses time-release polymer discs to deliver a different anti-cancer drug directly to the brain to fight malignant tumors in people.
Pending further lab research, clinical studies with malignant gliomas, the most common and deadly brain tumor, may begin in 1997, according to Michael A. Zasloff, M.D., Ph.D., executive vice president of Magainin.
Brain cancer causes a substance known as vascular endothelial growth factor (VEGF) to bind to cells lining brain blood vessels. VEGF causes the endothelial cells to multiply uncontrollably, thereby forming new blood vessels that allow the tumor to grow. Hopkins and Magainin scientists last week reported that squalamine appears to work by blocking a protein in endothelial cell membranes that is activated by VEGF and other growth factors.
The studies' other authors were Darin S. Epstein, B.A., and Eric P. Sinos, M.D., of Hopkins and Delwood Collins, Ph.D., and Jon Williams, Ph.D., of Magainin.