The drug R115777 (Zarnestra) (tipifarnib) produced responses that ranged from complete responses to improvement in blood counts in about one-third of 82 patients treated at seven different hospitals in the United States, Canada, and Europe, says the study ™s lead investigator, Razelle Kurzrock, M.D., a professor in the Department of Experimental Therapeutics at M. D. Anderson Cancer Center.

That level of response, as well as side effects that are well tolerated, can be a boon to the mostly elderly patients who develop the syndrome, Kurzrock says. It is one more drug that can be tried to help improve blood counts and prevent leukemia development in these patients, she says.

At the time the study began, there was no approved therapy to treat MDS, but recently, the FDA approved use of azacytidine (Vidaza), which is a chemotherapy drug administered subcutaneously. Zarnestra helps about as many patients as Vidaza, but for diseases like this, you need more than one drug because the syndrome is made up of numerous subtypes, Kurzrock says. If one drug doesn ™t help, then the other might; or they could potentially be used together.

Zarnestra belongs to a group of drugs known as farnesyl transferase inhibitors, which block enzymes needed for the activation of cancer-promoting proteins. While the drug was initially believed to act primarily on the ras gene, which is mutated in about 25 percent of MDS patients, recent studies including this one demonstrate that patients whose ras gene is normal can benefit, Kurzrock says. It has become apparent that Zarnestra regulates other important cancer genes, although we don ™t know which ones they are.

mdanderson

"SRF serves a very critical function in directing genes to develop an internal structure that acts sort of like the skeleton in the human body," Miano explains. "You can imagine that without a skeleton, our bodies would flop to the floor. Cells need the same structure and form in order to migrate, contract, and work properly."

Thus, although other scientists have defined hundreds of genes that may cause miscarriages due to cardiovascular defects, the latest research also links SRF for the first time to embryonic heart development. The National Heart, Lung and Blood Institute of the National Institutes of Health funded the research.

Miano's group plans to conduct further studies in mice to pinpoint the exact cause of death among the animals that lack the SRF protein. In addition, the team is searching for all of the genes directed by SRF. The long-tem goal of the research is to provide a foundation for genetic screening for all types of cardiovascular disorders, and perhaps a way to replace the faulty genes through targeted therapy.

Scientists studying a vital protein called Serum Response Factor (SRF) in mice have learned new and unexpected facts about SRF's role in early cardiovascular development, and how a defect in this gene may be an underlying cause in human miscarriages. The research provides a foundation for understanding how gene mutations may disrupt heart function, perhaps making some adults more susceptible to heart failure or irregular reactions to drugs.

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