Nimesulide, a cyclooxygenase-2 (COX-2) inhibitor, delays the progression of premalignant pancreatic lesions in mice, as per scientists at David Geffen School of Medicine at UCLA. While inflammation has been shown to be a factor in a number of forms of cancer, the scientists say this is the first study to demonstrate the effect of an anti-inflammatory COX-2 inhibitor on the development of pancreas cancer.

The study, reported in the August 1 issue of Cancer Research, a journal of the American Association for Cancer Research, suggests a potential role for COX-2 inhibitors in pancreas cancer prevention among high-risk patients. Pancreas cancer is one of the leading causes of cancer death in America over 33,000 Americans will likely die from the disease in 2007, as per projections from the American Cancer Society.

By inhibiting COX-2 in human patients, we may have an option to delay the progression of lesions, said lead author Guido Eibl, M.D., scientific director of the Hirshberg Laboratory of Pancreatic Cancer Research and adjunct assistant professor at UCLA.

Scientists believe pancreas cancer arises from abnormal tissues, or lesions in the pancreas, known as pancreatic intraepithelial neoplasias (PanINs). By stalling the growth of PanINs, scientists hope to slow the development of or prevent pancreas cancer.

COX-2, an enzyme which causes inflammation, is no stranger to cancer researchers. Studies of breast, colon, and pancreas cancers have led scientists to believe COX-2 plays a key role in the development and growth of tumors.

To study the effects of COX-2 on PanIN progression, Dr. Eibl and his colleagues focused on the KrasG12D mouse, an animal model that mimics the early stages of pancreas cancer. In the KrasG12D mouse, low-grade PanINs (stage I or II) begin to appear in the pancreas of mice at one month. Starting at six months, high-grade PanINs (stage III) can be found in the mouse pancreas. As per Dr. Eibl, most scientists agree that stage III PanINs are a direct precursor to pancreas cancer in humans as well as mice. Between 12 and 15 months, Dr. Eibl says the majority of KrasG12D mice will develop pancreatic tumors.

The UCLA scientists divided the mice into two groups one set received a nimesulide-enriched diet for 10 months; the other was offered only regular mouse chow. Their analyses revealed that the nimesulide diet greatly reduced the number of late-stage PanINs in KrasG12D (10 percent of pancreatic ducts had PanIN-2 or -3 in KrasG12D mice on nimesulide diet versus 40 percent of pancreatic ducts had PanIN-2 or -3 in KrasG12D mice on normal diet).

Because the pancreases of mice were analyzed at 10 months, before the typical appearance of pancreatic tumors, additional studies will be needed for scientists to conclude whether or not nimesulide can delay the onset of or prevent pancreas cancer.

With these results, I certainly wouldnt say everyone should be taking COX-2 inhibitors to protect against cancer, said Eibl. However, with additional studies, we may find COX-2 inhibitors could help prevent pancreas cancer in high risk populations.

Pancreas cancer is so deadly because it often goes undetected until its too late, said Dr. Eibl. If a patient is at a high-risk for developing pancreas cancer, a COX-2 inhibitor may offer some protection.

In the future, Dr. Eibl and others plan to study the long-term effects of nimesulide and additional COX-2 inhibitors on the onset and progression of pancreas cancer.


Posted by: Andria    Source

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