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Treatment Prolongs Life of Rats With Incurrable Brain Cancer

Treatment Prolongs Life of Rats With Incurrable Brain Cancer

The lives of rats with an incurable, rapidly progressing form of brain tumor, similar to glioblastoma in humans, is greatly extended through the use of two experimental anti-cancer techniques, new research shows.

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 excited 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 a recent issue of Cancer Research.

The Ohio State group combined an experimental technique for disrupting the blood-brain barrier with an experimental form of radiation therapy known as boron-neutron capture therapy (BNCT)

For this study, researchers temporarily disrupted the blood-brain barrier by delivering a highly concentrated mannitol solution to the blood vessels serving the brain. 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 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. 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.

The 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 through a vein in the belly; another group received the drug intra-arterially through the carotid artery in the neck; 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.

 
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