COLUMBUS, Ohio -- The lives of rats with an incurable, rapidly progressing form of brain tumor is greatly extended through the use of two experimental anti-cancer techniques, new research shows.
The results are important because the rat tumor is similar to glioblastoma, a fatal brain tumor in humans.
Rats given the glioblastoma-like tumor cells and left untreated died from the tumor after an average of 24 days. Rats receiving the experimental treatments, however, lived up to four times longer -- an average of more than 95 days -- and a number of rats seem to have been cured.
“We’re very exited about this,” said Rolf Barth, professor of pathology with Ohio State University’s Comprehensive Cancer Center and lead author for the study. “We really think that several animals were cured. These results are exciting because in 26 years of previous work at this institution, no animals with this tumor were ever cured.”
The study was published in the March 15 issue of Cancer Research.
Barth, Weilian Yang, a research scientist in Barth’s laboratory, and a team of researchers achieved the success by combining an experimental technique for disrupting the blood-brain barrier with an experimental form of radiation therapy known as boron-neutron capture therapy (BNCT).
The blood-brain barrier is a structural feature of the capillaries in the brain. The cells fit together extremely tightly, thereby preventing water-soluble molecules -- including anticancer drugs -- from passing out of the capillary and into the brain tissue unless the cells transport them there.
For this study, researchers temporarily disrupted the blood-brain barrier by delivering a highly concentrated sugar (mannitol) solution to the blood vessels serving the brain. The high sugar concentration causes the cells that form the capillary walls to shrink and pull away from one another. The capillary walls then become leaky, allowing drugs to enter the brain. When the sugar solution is no longer present, the capillary cells soon re-establish the blood-brain barrier.
Blood-brain barrier disruption is being tested in humans in several clinical trials, including one at Ohio State’s Arthur G. James Cancer Hospital and Research Institute, as a way to improve the treatment of brain cancer.
The second experimental radiation treatment, BNCT, uses boron-containing drugs that localize in tumor cells. The drug is administered and given time to localize in the tumor and be cleared from the rest of the body.
The tumor is then irradiated with a beam of neutrons. When neutrons strike the boron atoms, the boron atoms “capture” the neutrons and give off alpha particles that kill tumor cells. Because alpha particles travel only about the length of one or two cells, the damage they do is restricted to nearby cells. BNCT is already being used in Japan to treat superficial cancers, and a clinical trial of its use in cancer patients is under way at Brookhaven National Laboratory in New York.
Barth and Yang’s study tested two boron-containing drugs, sodium borocaptate (BSH) and boronophenylalanine (BPA). The study sought to determine if blood-brain barrier disruption would improve the delivery of the drugs to the brain and thereby improve the effectiveness of BNCT.
The study used six groups of animals, with 8 to 10 animals in each group. The scientists implanted 1,000 tumor cells into the brain of each of these animals.
“This is a tumor in which 10 tumor cells will invariably kill all of the animals,” said Barth.
Three of the treatment groups were given BSH. In one group, the drug was given intravenously (IV) through a vein in the belly; another group received the drug intra-arterially through the carotid artery in the neck, which is a more direct route; the third group received the drug through the carotid artery, plus blood-brain barrier disruption. BPA was given in the same three ways to the other three groups of animals. Two control groups were also used, with 18 animals in each group.
The tumors in the animals were then irradiated with a neutron beam at Brookhaven National Laboratory. Of the two drugs, BPA achieved the highest concentration in tumor cells and produced the most prolonged survival.
Barth, who together with Albert Soloway, professor of pharmacy, co-directs the BNCT program at the Ohio State’s Comprehensive Cancer Center, is working with Joseph Goodman, associate professor of surgery, and other members of the research team on a clinical study of the uptake of BSH in patients with malignant brain tumors.
They are also planning a study to determine if intra-arterial administration of BSH, possibly combined with blood-brain barrier disruption, can increase boron uptake in brain tumor patients.
Contact: Rolf Barth, (614) 292-2177; Barth.1@osu.edu
Written by Darrell E. Ward, (614) 292-8456;Ward.25@osu.edu