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Jewish World Review March 1, 2001 / 6 Adar, 5761

Lee Bowman

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Gene therapy prevents stomach cancer in mice

http://www.jewishworldreview.com -- RESEARCHERS have successfully prevented stomach cancer in mice using oral doses of gene therapy, a technique that could have potential use against several types of human cancer.

"This is the first time we've shown we can prevent cancer by using gene therapy,'' said Dr. Carlo Croce, head of microbiology and immunology at Thomas Jefferson University in Philadelphia and lead author of a report on the experiment published Tuesday in an online version of Proceedings of the National Academy of Sciences.

The treatment greatly reduced the incidence of stomach cancer in animals already prone to develop tumors and exposed to a cancer-causing substance, compared to a control group that wasn't given the treatment.

The researchers created mice lacking a gene called FHIT, which humans also have and which is known to contribute to several types of cancer when damaged. The gene has been linked to cancer of the stomach, esophagus, kidney, breast and lung.

Each mouse was then exposed to the carcinogenic chemical four weeks before therapy was started. Each of eight mice in three therapy groups received one dose of FHIT gene therapy with a different type or combination of virus-delivery system. (Weakened viruses are the most common method for putting gene treatments into cells.)

All 12 control mice developed several tumors. In the group that received the gene in an adenovirus, 50 percent developed tumors, while in mice that had the gene delivered using an adeno-associated virus only three of eight developed tumors. Two mice in the third group that got a combination of the two viruses died from pneumonia after they were treated.

"We were pretty surprised that it worked so well. We expected differences, but not so dramatic,'' said Kay Heubner, a co-author and professor of microbiology and immunology at Jefferson.

Further microscopic exams showed that the stomachs of all the control mice had been affected, while in the adeno-associated group, 56 percent of the mice stomach tissue samples were normal. The researchers believe that this type of virus may allow the FHIT gene to be active over a longer period of time.

The scientists said the technique could be a way to prevent and perhaps treat cancer in the early stages, but they cautioned that there are a number of hurdles that must still be overcome, including finding ways to get the viruses - and thus the genes - into other types of tissue, such as the lungs, liver and kidneys.

Many experts believe this sort of gene therapy represents not so much a potential cure for cancer, but rather another form of treatment added to existing tools like chemotherapy and radiation.

But having a technique that appears able to halt development of cancer in high-risk individuals by even temporarily correcting a gene deficit is significant. By decoding the human genetic code, scientists are becoming increasingly able to detect missing or defective genes that make individuals more likely to develop certain types of cancer.

The researchers are already working on new experimental animals with the FHIT gene deleted to make them prone to both cervical and lung cancer.

Huebner also noted that more study is needed "to determine at what point the intervention would still work. If we started the treatment later in the tumor development process, would it still be effective, and how effective?''

The scientists also want to know if giving the treatments to animals earlier in life could further reduce the odds of developing tumors.
On the Net: http://www.pnas.org

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