Public Release: 

Cancer prevention news tips

Johns Hopkins Medicine

The following news tips are based on abstracts prepared for the American Association for Cancer Research 4th International Conference on Frontiers in Cancer Prevention Research in Baltimore, Maryland, October 30 - November 2, 2005. To follow up on the tips, contact Vanessa Wasta at 410-955-1287 or Embargo dates and times are noted with each news tip.

(Embargoed for Release until 9 AM, ET, Monday, October 31, 2005)
Abstracts #2597 and #3442

Researchers in Japan and Baltimore have found that a daily serving of broccoli sprouts can improve chronic bacterial gastritis, a serious disorder that causes inflammation of the stomach lining. Without treatment, gastritis may lead to ulcers and in some cases, stomach cancer.

Unlike the green, treelike florets common on dinner plates, three-day-old sprouts from broccoli seeds contain ultra high concentrations of sulforaphane, a compound with documented cancer prevention effects. Now, Hopkins investigators say there is some evidence the compound has antibiotic properties to treat the bacteria that causes gastritis. Forty research participants in Japan were randomly assigned to eat 100 grams daily (enough to fill the palm of a hand) of either broccoli sprouts or a sulforaphane-free vegetable. Researchers measured levels of blood proteins that are specific indicators of gastritis and inflammation, and they measured participants' stomach colonization with the bacterium Helicobacter pylori. This year's Nobel Prize in Medicine went to the scientists who some years ago demonstrated that stomach ulcers are almost always caused by H. pylori infection, and that a course of antibiotics could cure most of them.

"The indicators of bacterial infection and gastritis were significantly reduced in the group that ate broccoli sprouts," says Jed Fahey, M.D., Sc.D., a research faculty member at Johns Hopkins, who recently discovered that sulforaphane had potent antibiotic activity against H. pylori in test tubes.

When broccoli-sprout eaters stopped their daily dose at the end of the study, gastritis and infection rates rose to pretreatment levels.

"H. pylori infection is especially prevalent in places with crowded living conditions and poor sanitation where it causes high rates of stomach cancers and other gastric disorders," says Fahey, who participated in the current study with Akinori Yanaka, M.D., Ph.D., at the University of Tsukuba, Japan. "In many developing regions with limited health care resources, an effective dietary change may be much more practical than prescribing a drug to reduce rates of certain illnesses."

The researchers will conduct longer-term studies to determine whether broccoli sprouts can prevent stomach cancer in people at risk for the disease.

In another sulforaphane study in mice, Johns Hopkins researchers say that applying broccoli-sprout extract to the skin may prevent skin cancers caused by the sun.

The scientists simulated the kind of skin damage that a person might sustain from the sun by exposing mice to UV light twice a week over 20 weeks. Then, each day (five days/week) they applied a few drops of an extract of broccoli sprouts on the backs of the mice and waited for tumors to appear. After 11 weeks, all of the mice that did not receive the extract developed tumors. At that point, only half of the mice receiving the extract had skin tumors.

"We believe sulforaphane, the cancer-preventive compound in broccoli sprouts, increases the levels of a variety of enzymes in the body that protect against cancer," says Albena Dinkova-Kostova, Ph.D., research associate at Johns Hopkins. "Sulforaphane can also decrease inflammation and eliminate harmful types of oxygen molecules and damaged cells."

The Hopkins researchers will conduct more tests in mice to determine whether broccoli sprout extracts can prevent skin cancer before sun damage occurs. They also hope to test the extract on organ transplant patients, who are at high risk for skin cancers.

Under a licensing agreement between Brassica Protection Products, LLC (BPP) and the Johns Hopkins University, Drs. Paul Talalay (a coauthor on Abstract #2597) and Fahey are entitled to shares of royalty received by the University on sales of products described in this article. Drs. Talalay and Fahey own BPP stock, which is subject to certain restrictions under University policy. Drs. Talalay and Fahey are unpaid consultants to the company. Dr. Talalay's son is the Chief Executive Officer of BPP and owns BPP stock. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest policies.

(Embargoed for Release until 1 PM, ET, Tuesday, November 1, 2005)
Abstract #2497

A new study shows that a synthetic version of a plant extract prevents mold toxin-induced liver cancer in rats. The extract, a derivative of oleanolic acid, is a building block of many plants, including herbs, and has known anti-inflammatory effects.

Recently created by chemists at Dartmouth College, the man-made version of oleanolic acid used in the study is dubbed CDDO-Im*. Investigators at Johns Hopkins teamed up with the Dartmouth chemists to determine whether the compound could help flush out of the body chemicals that trigger the development of liver cancer.

The researchers used rat models that simulate precancerous liver tumors caused by a carcinogen called aflatoxin. Aflatoxin is produced by microscopic molds found on dietary staples, such as corn and peanuts. It also is known to cause liver cancer in people infected with hepatitis B.

"We know that aflatoxin can't be eliminated from our environment, but we can try to diminish its effects," says Thomas Kensler, Ph.D., professor of environmental health sciences at the Johns Hopkins Bloomberg School of Public Health.

In the Hopkins-Dartmouth study, the amount of precancerous tissue in the rats totaled approximately 1 percent of liver volume - enough to cause full-blown cancer. Very low doses of CDDO-Im reduced that fraction by 85 percent. Larger doses of the compound virtually obliterated all signs of precancerous tissue.

The team's research on gene expression patterns and knock-out mice also revealed that CDDO-Im works by activating a protein called Nrf2, the master switch that controls other genes crucial to cell-survival. "Essentially, CDDO-Im may make cells more resistant to aflatoxin," says Kensler.

Compared with other compounds used in clinical studies to prevent liver cancer, the researchers say that a much smaller dose of CDDO-Im may be needed to have an impact on preventing the disease. Studies in humans are not yet planned.

*CDDO-Im (1-[2-cyano-3, 12-dioxooleana-1,9 (11)-dien-28-oyl] imidazole)


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