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Cancer cells can compress blood vessels, block entry of drugs

A growing tumor needs an increased blood supply for its proliferating cells. But the implications of tumor-related angiogenesis the growth of new blood vessels are much more complex than many investigators have realized. Although these new vessels are required to nourish the tumor itself, they are disorganized and abnormal and can actually block therapeutic agents from reaching malignant cells.

In the Feb. 19 issue of Nature, researchers from Massachusetts General Hospital (MGH) describe how proliferating cancer cells compress both blood and lymphatic vessels within tumors. The findings suggest new strategies for improving the success of cancer treatment. Related studies in the February issue of Nature Medicine provide more information about improving the delivery of anticancer drugs to tumor cells.

"We've known for several years that internal pressure can make it difficult for many drugs to penetrate into a tumor," says Rakesh Jain, PhD, director of the Edwin Steele Laboratory in the MGH Department of Radiation Therapy, senior author of the Nature and Nature Medicine papers. "Much of our work has focused on fluid pressure within tumors, but this was the first look at solid pressure."

As described in the Nature study, fluid pressure had been assumed to be the force compressing vessels within tumors, but actual fluid pressures inside both tumors and their blood vessels are almost equal. The MGH team investigated whether solid pressure exerted by proliferating cancer cells could compromise blood supply in the same way that stepping on a hose cuts off the flow of water. Using human tumors implanted in mice, the researchers administered diphtheria toxin, which kills tissue from humans but not from mice, to selectively destroy cancer cells.

Analysis of the toxin-treated tumors found that both blood vessels and lymphatic vessels looked much more open than did vessels from untreated tumors, which were largely collap
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
18-Feb-2004


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