New uses for familiar bugs could advance cancer cure

0 Comments | Insight on the News, March 9, 1998 | by Phil Berardelli

Two common strains of bacteria, salmonella and H. pylori, have been found to play roles in the growth of tumors. Researchers hope genetic engineering and better sanitation will prevent cancer in humans.

Science has been struggling for years to find ways to use living organisms to deliver anticancer substances to tumor sites, with limited success.

Now it appears that a normally dangerous bacterium might be a prime candidate for the job: A genetically disarmed strain of salmonella has been used to retard the growth of melanoma tumors in laboratory animals.

Researchers at the Yale University School of Medicine and at Vion Pharmaceuticals Inc., of New Haven, Conn., tested the common household pathogen salmonella on a variety of human tumor cells. They discovered that salmonella are "quite skilled" at seeking out and invading dense tumor tissues. More importantly, the bacteria are equally effective with different varieties of cancer.

Unlike viruses and other potential cancer-fighting substances, which must be manually injected into each tumor site, salmonella only need be introduced into the bloodstream. For reasons that still are not well understood, when the bacteria are carried inside a tumor, they will propel themselves into the deepest areas of the tissue, where they begin to multiply rapidly -- up to a thousandfold within 24 hours.

Salmonella's potential danger -- a powerful toxin called LPS which accumulates in the liver and can cause an often-fatal condition called septic shock -- can be neutralized by genetic engineering. This makes the mutant strains of the bacteria vulnerable to the body's immune system. They can't grow except within tumor cells.

So far, experiments on laboratory mice have been promising but not flawless. The altered bacteria seem harmless to the host animals, but they only retard, not stop, the growth of tumors. The cancerous mice injected with salmonella lived only an extra three or four weeks. Researchers hope to arm the organisms with anticancer genes so they can destroy tumors instead of coexisting with them.

Meanwhile, British scientists have established a link between infection of the stomach by a common bacteria, called H. pylori, and the development of stomach cancer. Researchers tested stored blood-serum samples from 21,000 professional men that had been collected during routine physical exams by BUPA, Britain's largest private health insurer. They found that the percentage of samples that tested positive for H. pylori antibodies was much higher in men who eventually developed stomach cancer than those who did not -- 68 percent vs. 37 percent.

There is a logical connection, according to researchers. H. pylori makes its home among the cells lining the stomach, protecting itself by producing an enzyme that acts like a "raincoat from stomach acid." Over time, the bacteria erode the stomach lining, causing peptic ulcers. After about age 50, people with stomachs carrying the bug become vulnerable to cancer.

Stomach cancer is the second-leading cause of cancer death worldwide, behind lung cancer.

It is particularly prevalent in Asia, South America and Africa, where H. pylori infects up to 40 percent of the population. The British researchers believe that stomach cancer could be reduced by stepped-up screenings for H. pylori and treatment with a combination of common medications and antibiotics.

Other researchers aren't so sure. Attempts have been made by the United Nations' World Health Organization to combat H. pylori in selected areas, without success. Researchers suspect the reason is poor sanitation, which makes reinfection easy. Since no immunization is yet available for H. pylori, improving sanitary conditions may be the best way to combat its effects.