For the millions of cancer survivors in the United States, emerging from surgery cancer-free is the ultimate victory. But many patients who clear the hurdle of cancer trauma will subsequently face a lifetime of swelling and discomfort, caused by an untreatable buildup of fluid in their tissues.
A team at the Stanford University School of Medicine has created an animal model for this complex condition, called lymphedema, taking the first steps toward understanding its behavior. Their results, which will appear in the July 17 issue of Public Library of Science-Medicine, indicate lymphedema is characterized not just by the presence of swelling, but by a profound, accompanying inflammation. This finding suggests drug therapies could one day be used to treat this disease.
"Ten million people in the United States have lymphedema. It's heartbreaking that the disease goes unacknowledged or unrecognized because doctors simply have no treatment to offer," said Stanley Rockson, MD, associate professor of medicine (cardiovascular) and senior author of the study. "This study opens the door to the likelihood of effective therapies."
Rockson said between 15 and 30 percent of breast cancer survivors develop lymphedema from surgery-induced damage to the lymphatic system -- a network of tissues and cells that make and store cells to fight infection. When surgery disrupts this circulatory system, protein-rich fluid collects in the tissue of the affected limb. This stagnant liquid bloats the tissue and impairs limb mobility, ultimately creating a cesspool for infection.
Current treatments for lymphedema involve bandaging the affected area or wearing tight-fitting garments to compress the swelling. Massaging can also help improve lymphatic flow. However, such measures are temporary, Rockson said, and provide little relief.
"It's like the iron lung for polio -- it works, but it's certainly no way to live," he said.
In this study, Rockson and his co-authors generated a mouse model to simulate human-acquired lymphedema. The model was tested using microscopic imaging and molecular-level techniques to find a molecular fingerprint or signature of the disease. Mouse tails were used for the model because of their rich lymphatic network -- a simple substitute for the arm, according to Rockson.
The researchers were able to trace lymphatic cell flow by injecting luciferase, the enzyme that gives fireflies their glow, into the mouse tails. Using a dynamic imaging technique, the scientists observed cell traffic slowing to a crawl in mice with lymphedema. At the molecular level, the researchers used a microarray chip to determine which of the mouse genes were active.
"Much to our delight, only 600 to 700 of the genes had changed," Rockson said, corresponding to about 1 percent of the 55,000 genes in a mouse. "This will allow us to determine whether we can treat lymphedema with a drug or compound that will revert the patient to normal behavior."
"From a patient perspective, it's exciting to see that we are moving beyond bandages and massage therapy," said Wendy Chaite, president and founder of the Lymphatic Research Foundation, a nonprofit organization based in East Hills, N.Y. Chaite, whose daughter was born with lymphedema, founded the organization out of frustration with the lack of treatment available for the disease.
"This study is a springboard for a lot of future investigations," she added. "Prior to this decade, people were not looking at this disease from the standpoint of 21st-century tools and technologies."
Rockson said the next step is developing viable therapies for humans. His team has targeted six classes of drugs for study, one of which has already been tested.
"Within the next 12 to 24 months we could be at the stage of testing in human populations," Rockson said.