Dr. Jian-Wei Gu came to Mississippi to study the cardiovascular system with a special interest in the process of blood vessel growth.
So how does a cardiovascular physiologist attract national headlines about his research in cancer?
According to Gu, assistant professor of physiology and biophysics at the University of Mississippi Medical Center, it was completely by accident.
Reports of Gu’s research have appeared in USA Today, Science News, the New Scientist and on CBS News. It was big news because Gu has done what many scientists before him have failed to do: describe the mechanism by which alcohol consumption causes tumor growth.
“Scientists have known for a hundred years that there was a strong association between alcohol consumption and several types of cancer,” Gu said. He cites a study from Paris in 1910 that showed that 80 percent of patients with cancer of the esophagus or gastric track were alcoholics.
More recently, epidemiological studies show a strong correlation between alcohol consumption and cancer of the mouth, pharynx, larynx, esophagus, liver, and large bowel. Alcohol consumption seems to be a risk factor even for breast cancer. But experiments in the lab have failed – until now – to show the effects in animals that observers knew to be true in humans.
The problem, it turns out, was that investigators were using too much alcohol.
“Most all the previous studies used alcohol concentrations of 20 percent, far more than the equivalent human consumption,” Gu said. The animals wasted away but they didn’t show abnormal tumor growth, he said.
Gu used alcohol concentrations of one percent, about the equivalent of one or two drinks a day in humans, or moderate alcohol consumption. Using what he terms “physiologically relevant” levels of alcohol, he stimulated tumor growth in both chick embryos and in mice.
Gu came to Mississippi in 1995 to work on angiogenesis, or blood vessel growth, and what stimulates or controls it. Seven years ago, working in the lab, he and his colleagues noticed that the growth factor that stimulates vessel growth (vascular endothelial growth factor or VEGF) increased “unexpectedly” in certain cell cultures.
They determined that it was the alcohol they used as a solvent, in very low concentrations, that caused the increase in the growth factor.
That serendipitous finding by Gu in 2000 led to the study in chick embryos and, most recently, to a study showing that melanoma cancers in mice grew significantly faster and larger in the mice who consumed the equivalent of one or two alcoholic drinks a day than the mice that received no alcohol.
The mice used in the most recent study were given drinking water that had an alcohol concentration of one percent for 12 hours. The next 12 hours, they received water with no alcohol. Another group of mice received no alcohol in their water.
After a week, Gu and his colleagues inoculated all the animals with mouse melanoma cells. Three weeks later, the tumors were removed to be analyzed. All the mice had tumors, but the mice given alcohol had tumors that had progressed much more rapidly than the mice that had no alcohol. The larger tumors also had more blood vessel growth.
Dr. Thomas Adair, professor of physiology and biophysics and Gu’s mentor when he came to Mississippi, said that Gu’s findings have been confirmed by other scientists.
“When he presented his findings at a FASEB (Federated Societies for Experimental Biology) meeting, someone from a group in San Diego came up to me afterward and told me they had found the same thing in their lab and didn’t know what to make of it. They went back and did a study on rats and found the same thing.”
Angiogenesis is an area of keen interest for its application to cancer therapy. Right now, Adair estimates there may be as many as 40 drugs that act by controlling angiogenesis in clinical trials.
But angiogenesis isn’t necessarily pathological, according to Adair. Stimulating angiogenesis would be helpful in repairing heart tissue damaged by a heart attack or in wound healing.
Gu’s research is funded by the National Alcohol Abuse and Alcoholism Institute of the National Institutes of Health (NIH), the National Heart, Lung and Blood Institute of NIH and the American Cancer Society.
— Janis Quinn (3-12-07)
Contributor: Don Phillips