Laboratory studies at Johns Hopkins have dramatically confirmed the power of a chemical discovered from the liver of sharks to slow the formation of new blood vessels destined to feed brain cancers as well as other tumors.
Squalamine, previously shown to have antibiotic and anti-cancer activity, inhibited the growth of brain cancers called gliomas implanted in the flanks of rats by disabling blood vessel growth, or angiogenesis, say the authors of the studies, published in the July 1 issue of the journal Cancer Research.
"Our results suggest that squalamine may be well suited for humans in the treatment of brain tumors and other diseases characterized by and dependent on new blood vessel growth," says Henry Brem, M.D., director of neurosurgical oncology at Hopkins and senior author of the study. "It dramatically slowed blood vessel formation without damaging healthy cells or embryonic development."
Named for the shark genus Squalus, squalamine was discovered in 1992 by scientists who founded Magainin Pharmaceuticals, which processes the chemical and funded the Hopkins studies. Squalamine is the first of a new class of naturally occurring molecules, aminosterols, under development for human therapies.
Squalamine is isolated from the tissues of the dog shark. It blocks or interferes with several steps in a cascade of events involved in blood vessel growth. Based on the Hopkins laboratory work, it is currently in Phase I clinical trials at the University of Texas (San Antonio) and at Georgetown Cancer Center.
In laboratory tests, squalamine proved to be as effective as the chemotherapeutic agent carmustine in slowing the growth of gliomas, the most common and deadly brain tumors, in rats. Squalamine also slowed the growth of new blood vessels caused by tumors in rabbits' eyes, slowed the growth of endothelial cells in rat brain tissue and constricted the tiny blood vessels in chick embryos. The latter vessels mimic those of tumors.
The study's other authors were Allen K. Sills Jr., M.D.; Betty M. Tyler; Darin S. Epstein; Eric P. Sipos, M.D.; John D. Davis, M.D.; Mark Donowitz, M.D.; and John Laterra, M.D., Ph.D., of Hopkins; Simon Pitchford of Molecular Devices Corp., Sunnyvale, Calif.; Francis H. Gannon of the Hospital of the University of Pennsylvania, Philadelphia; and Jon I. Williams, Ph.D.; Kimberly Chesire, William A. Kinney, Tessa L. Chao, and Michael Zasloff, M.D., Ph.D., of Magainin Pharmaceuticals, Plymouth Meeting, Pa.
Some of the cells used in laboratory tests and their derivative lines are the property of Neurotech, S.A., Paris, France. Laterra owns stock in Neurotech, an arrangement that has been reviewed and approved by the Johns Hopkins University Office on Conflict of Interest.
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Journal
Cancer Research