LONG BEACH, California -- Blood vessels, literally the lifelines in our bodies, are key to delivering the nutrients our organs need to survive. But they have a deadly side in that they also feed cancerous growths.
Treatments for halting the growth of cancer-feeding blood vessels could be key to treating tumors and could also have positive effects on reducing obesity, according to Dr. William Li, head of the Angiogenesis Foundation, a non-profit behind much of the research into these new treatments.
The treatments inhibit a process that occurs naturally in our bodies, called angiogenesis.
Li, speaking at the Technology, Entertainment and Design conference Wednesday, said the adult human body is packed with 16,000 miles worth of blood vessels, including 19 billion capillaries.
We get most of our blood vessels when we're still in the womb. As adults blood vessels don’t normally grow except in a few circumstance – in women, they grow every month to build the lining of the uterus; and during pregnancy, they form the placenta. Blood vessels also grow after injury, building under a scab to heal a wound.
The body has the ability to regulate the amount of blood vessels that are present at any given time; it does this through an elaborate system of check and balances involving stimulators -- the basis for angiogenesis -- and inhibitors
When we need a brief burst of blood vessels the body releases stimulators that act as natural fertilizer to stimulate new blood vessels. When those extra blood vessels are no longer needed, the body prunes them back to baseline, using naturally occurring inhibitors.
For a number of diseases, however, there are defects in the system where the body can't prune back those extra blood vessels or grow enough new ones in the right place at the right time. In these situations angiogenesis is out of balance. When angiogenesis is out of balance a myriad of diseases result --- insufficient angiogenesis (not enough blood vessels) can lead to wounds that don't heal, heart attacks, poor circulation in legs, death from stroke, nerve damage, hair loss, erectile dysfunction.
On the other hand, extensive angiogenesis (too many blood vessels) drives diseases. We see this in cancer, blindness, arthritis, psoriasis, obesity, Alzheimer's disease, endometriosis, and other diseases Li said.
More than 70 major diseases affecting more than a billion people worldwide share abnormal angiogenesis as their common denominator. In particular, angiogenesis is a hallmark of every type of cancer.
Cancers don't start out with a blood supply. Instead, they begin as small, microscopic nests of cells that will grow only to one half a cubic millimeter in size – the tip of a ballpoint pen. Without a blood supply, most of these cancers will never become dangerous.
Cancer cells mutate and gain the ability to release lots of angiogenesis factors that tip the balance in favor of blood vessels invading the cancer. Once those vessels invade a tumor, it can expand, and the same vessels feeding the tumor allows cancer cells to then exit into the circulation as metastases. This late stage of cancer is the one at which the disease is most likely to be diagnosed but the most difficult to treat.
But if angiogenesis is a tipping point between a harmless cancer and a harmful one, then one major part of treating cancer would be cutting its blood supply.
There are already pioneer treatments available for humans -- called anti-angiogenic treatments -- that became available starting in 2004, using 12 different drugs to treat 11 different cancer types.
Another 100 or so drugs are in the pipeline.
The results of the treatments are that there has been a 70 to 100 percent improvement in survival for people with kidney cancers, colo-rectal cancer, and gastrointestinal tumors. For other cancer types, the improvements have only been mild. The reason, Li said, was generally due to treating cancer too late in the game, when it's already established or spread.
He realized the answer to cancer could be preventing angiogenesis through diet, since diet accounts for 30 to 35 percent of environmentally caused cancers.
So he started looking at what people could add to their diet that's naturally anti-angiogenic to boost the body's and beat back the blood vessels. In other words, can we eat to starve cancer?
What he found was that nature has laced a large number of foods, beverages and herbs with naturally occurring inhibitors of angiogenesis.
He and his researchers built a simulator to test the effect different foods (see list of foods at right) would have on blood vessels at concentrations that are available through eating, rather than concentrated, encapsulated forms. The tests showed that an extract of resveratrol, found in red grapes and red wine, would inhibit abnormal angiogenesis by 60 percent. Extracts from strawberries and soybeans had similar benefits.
They also tested four teas -- a Chinese jasmine tea, Japanese sencha, Earl Gray and a blend of the Chinese jasmine and Japanese sencha teas. The teas varied in their potencies. The Chinese Jasmine and Japanese sencha teas were each less potent than the Earl Grey tea. But when they combined the two teas, the combination was more potent than either one alone or than the Earl Grey tea. This means there's food synergy, Li said, and that foods likely work best in combination to create benefits.
The Angiogenesis Foundation is in the process of measuring a long list of foods to determine the potencies in different strains and varieties and are creating a rating system to score food according to its anti-angiogenic, cancer-preventative properties.
They've also tested the potency of traditional cancer drugs on angiogenesis. They looked at statins, non-steroidal anti-inflammatory drugs and a few others and found that they also inhibit angiogenesis. And when they compared the dietary factors against the drugs, the diets held their own and in some cases surpassed the drugs in their potential to inhibit angiogenesis. Soy, parsley, garlic, grapes, berries were all high performers in this regard.
So what is the evidence in people that eating certain foods can reduce angiogenesis and cancer?
He cites a study that followed 79,000 men over 20 years, which found that men who consumed cooked tomatoes 2 to 3 times a week had a 40 to 50 percent reduction in their risk of developing prostate cancer. In those men who did develop prostate cancer the ones who ate more servings of tomato sauce had fewer blood vessels feeding their cancer. Tomatoes, of course, are a good source of lycopene, which is anti-angiogenic.
They're now studying the role of a healthy diet with Dean Ornish, the University of California at San Francisco and Tufts University in Boston on the role of a healthy diet on markers of angiogenesis in the bloodstream.
Li says the research could impact consumer education, food services, public health policies and even the insurance industry and, for many people in the world, dietary cancer prevention may be the only practical solution they can afford. Ultimately, he said what we eat could turn out to have the cancer-fighting benefits of taking chemotherapy three times a day.
But the research on anti-angiogenesis, also has relevance for tackling obesity. It turns out that fat is highly dependent on angiogenesis, because like a tumor, fat grows when blood vessels grow.
The question was, could they shrink fat by cutting off its blood supply?
The researchers took a genetically obese mouse -- the ob\ob -- that eats nonstop until it turns it looks like a furry tennis ball. When they gave the mouse an angiogenesis inhibitor, the mouse lost weight. Once treatment stopped, the mouse gained back the weight.
"In effect, you can cycle the weight up and down simply by inhiiting angiogenesis," Li said. "So this approach we're taking for cancer prevention may also have an application for obesity."
One caveat – they can't take obese mice and make them lose more weight than what their normal mouse weight is supposed to be.
"In other words, we can't create supermodel mice," Li said.
Photo: Cynthia Howe
