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March 6, 2003


Gene seems to help control cell growth of colorectal cancer

Researchers at the University of Pittsburgh Cancer Institute (UPCI), in collaboration with Johns Hopkins University, have found that a recently discovered gene plays an essential role in mediating apoptosis, or cell death, in colorectal cancer cells.

The results were published in the Feb. 18 issue of Proceedings of the National Academy of Sciences.

The gene, PUMA, or p53 up-regulated modulator of apoptosis, is controlled by p53 — a tumor-suppressing gene that prevents normal cells from turning into life-threatening tumor cells. Previous research has determined that damage to p53 is fundamental to the development of a vast majority of cancers, and inactivation of the growth-controlling function of p53 is critical to the growth and spread of most cancers.

Lead investigators Lin Zhang, Pitt assistant professor of pharmacology, and Jian Yu, assistant professor of pathology, found that if PUMA is deleted in colorectal cancer cells, cell death is prevented.

“This research results from our interest in looking at how cancer cells die when treated with anti-cancer therapies and why chemotherapy often fails to destroy cancer,” Yu said. “We have learned that when we get rid of PUMA in cancer cells, the cells are more resistant to dying compared to their counterparts that have intact PUMA.”

“Given these findings,” Zhang said, “our next step is to look for compounds that elevate the level of PUMA in colorectal cancer cells, enabling us to test promising new therapies for cancer. PUMA itself also is an attractive target for gene therapy. At UPCI, we are trying to expand these approaches to a variety of cancers.”

This study was funded, in part, by the National Institutes of Health.


Diagnostic antigen found for Chagas disease

Researchers from Pitt and the Federal Universities of Ouro Preto and Minas Gerais in Brazil have identified recombinant T. cruzi complement regulatory protein (rCRP) as a highly accurate diagnostic antigen for Chagas disease, a major public health concern in Latin America.

The Pitt team, led by Karen Norris of immunology, cloned the gene and purified the recombinant protein necessary for the research. When the Universidade Federal researchers used it to test blood samples of patients with Chagas disease or Leishmania infections, they found that the rCRP-based enzyme-linked immunosorbent assay (ELISA) had a 100 percent sensitivity and specificity compared to conventional tests.

According to Wendell Meira (formerly of Universidade Federal, and currently a research associate in Norris’s lab), the results indicate that rCRP ELISA was able to discriminate between chronic chagasic patients and non-chagasic individuals.

Chagas disease is a South American form of trypanosomiasis caused by the protozoan Trypanosoma cruzi.

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