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Pancreas Cancer News and Archives | |
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For educational purposes only; not to be relied upon. Please read Pancreatica Disclaimer | |
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A Selective COX-2 Inhibitor
Differentially Modulates Tumor Angiogenesis and Growth in COX-2
Expressing and COX-2 Lacking Pancreatic Cancer in vivo: Abstract
No. 4792
In their studies, the researchers found that the anti-inflammatory drug nimesulide triggered the growth of blood vessels, or angiogenesis, in human pancreatic cells that do not express an enzyme called COX-2. Nimesulide belongs to a class of so-called "super aspirins" that primarily work by blocking COX-2, thus inhibiting inflammation seen a variety of ailments including arthritis and even some cancers. In fact, the UCLA study confirmed that nimesulide actually inhibited angiogenesis and tumor growth in pancreatic tumors that express COX-2. "Basically, for the first time, we have shown that a selective COX-2 inhibitor can simulate tumor growth," said Guido E. Eibl, M.D., a researcher in the Hirshberg Pancreatic Cancer Laboratory at the UCLA School of Medicine. "However, its effects, depend on whether the tumor expresses COX-2 or not," he added. Depending on the study, roughly 10-40 percent of all pancreatic tumor cells are considered COX-2 negative, while all others express COX-2. "These studies suggest that patients can be treated with selected COX-2 inhibitors, but only based on the COX-2 expression profile of their pancreatic tumor," said Eibl. Such findings are significant for a disease that is considered among the most lethal of all tumors, with a mortality rate in excess of 95 percent. In the United States, pancreatic cancer now ranks fourth and fifth as a cause of cancer death in men and women respectively, with about 25,000 new cases of pancreatic cancer diagnosed each year. Chemotherapy has not resulted in significant survival benefit, suggesting the need for new molecular targets for prevention and treatment of this disease. In the UCLA study, COX-2 negative and positive human pancreatic tumor cells were injected in the flanks of nude mice, which were then treated with nimesulide. The scientists found that in the COX-2 positive mice, the drug inhibited a factor needed for the growth of blood vessels (VEGF), but actually increased human VEGF levels in the COX-2 negative mice. The results showed widespread growth of blood vessels in the COX-2 negative mice, along with increased production of pancreatic cancer cells. "The increase in VEGF production has predominantly only an effect in vivo, where it can act on endothelial cells," said Eibl. "So it may very well be possible that the overall effects of nimesulide, or any other COX-2 inhibitor for that matter in vivo, reflects a balance between direct effects on the cancer cells and indirect effects on the interaction between the cancer cells and host tissue." Eibl said his team plans to test other COX-2 inhibitors in animals to see if other drugs in this class have the same impact on tumor growth as nimesulide. "Based on in vitro data, we feel confident that we would find comparable results in vivo, although the studies still must be done," said Eibl.
Founded in 1907, the American Association for Cancer Research is a professional society of more than 22,000 laboratory, translational, and clinical scientists engaged in all areas of cancer research in the United States and in more than 60 other countries. AACR's mission is to accelerate the prevention and cure of cancer through research, education, communication, and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. AACR's Annual Meetings attract more than 15,000 participants who share new and significant discoveries in the cancer field. Specialty meetings, held throughout the year, focus on the latest developments in all areas of cancer research.
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