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COX-2 inhibitors delay pancreatic cancer precursors in mice

Published on August 1, 2007 at 11:42 PM · No Comments

Nimesulide, a cyclooxygenase-2 (COX-2) inhibitor, delays the progression of precancerous pancreatic lesions in mice, according to researchers at David Geffen School of Medicine at UCLA.

While inflammation has been shown to be a factor in many forms of cancer, the researchers say this is the first study to demonstrate the effect of an anti-inflammatory COX-2 inhibitor on the development of pancreatic cancer.

The study, published 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 pancreatic cancer prevention among high-risk patients. Pancreatic cancer is one of the leading causes of cancer death in America – over 33,000 Americans will likely die from the disease in 2007, according to 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 .

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

COX-2, an enzyme which causes inflammation, is no stranger to cancer researchers. Studies of breast, colon, and pancreatic cancers have led researchers 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 colleagues focused on the KrasG12D mouse, an animal model that mimics the early stages of pancreatic 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. According to Dr. Eibl, most researchers agree that stage III PanINs are a direct precursor to pancreatic cancer in humans as well as mice. Between 12 and 15 months, Dr. Eibl says the majority of KrasG12D mice will develop pancreatic tumors.

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