By Julia Ferrante
LEWISBURG, Pa. - In a discovery that could aid in cancer treatment, a team of researchers at Bucknell University, Massachusetts General Hospital and Harvard Medical School have found a better way to map blood vessels in normal and cancerous tumors.
James Baish, a professor of biomedical and mechanical engineering, and clinical collaborators in Boston, published their findings in a paper, "Scaling rules for diffusive drug delivery in tumor and normal tissues," in the February 2011 edition of Proceedings of the National Academy of Sciences. The research team reveals in the paper two mathematical formulas to determine the shape and space between blood vessels in tumors, calculations that could allow drug companies to better design and doctors to more precisely prescribe cancer-fighting drugs. || See full text of article or PDF.
"What we came up with basically was two numbers that can be used to describe the vascular network," Baish, Class of '79 said. "One of our calculations measures how far it is between two vessels. The other is a measure of whether the blood vessels are mostly parallel or dominated by holes. We argue that if you know those two numbers, you know most of what you need to know about vessels."
Order in the chaos
While healthy vessels distribute blood via an orderly, tree-shaped structure with tapered branches, Baish explained, the blood vessels in tumors are unwieldy and unpredictable, presenting challenges for drug delivery. The collaborators discovered through a combination of mathematical and experimental research, however, that there is some predictability in the chaos.
Many doctors prescribe antiangiogenic drugs to modify tumor blood vessels so that the tumors will better absorb cancer-fighting drugs, Baish explained.
"If you want to treat the tumor with a drug, it is difficult to get to the cancer cells," he said. "When you can find the right substance to modify the blood vessels, we call it normalization, where you give a drug that tries to reverse this chaotic mess. Then, you can use cytotoxins, more traditional chemotherapy drugs. If you do it right, you can hit the nasty stuff more effectively."
Slowing the spread
In the study, experimental researchers led by Rakesh K. Jain at the Edwin Steele Lab for Tumor Biology at Mass General bred thousands of mice to be immune-deficient. The mice developed human tumors. Baish, whose research at Bucknell focuses on the geometry of blood vessels, assessed the efficiency of vessels in delivering oxygen and drugs to tumors. Tumors are surrounded by blood vessels that multiply fast, break down and change day to day.
"When cancer cells can stimulate the growth of new blood vessels, there are tiny things you can observe," Baish said. "Some drugs alter the blood vessels. Some are toxic. This gives us some idea of how effectively we can get drugs to their intended target. It does not tell a doctor what to do, but it can provide guidance."
Better targeting cancer cells reduces the chances that the cells will multiply and that the cancer will spread, Baish said.
"This is far from saying this is a cure," he said. "It's a small step in an attempt to solve a difficult problem. This study lays out a new theoretical framework for tackling a problem."
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