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COX-2 inhibitors delay pancreatic cancer precursors in mice
August 02, 2007PHILADELPHIA-- 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,"ť 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.
The UCLA researchers 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 researchers to conclude whether or not nimesulide can delay the onset of or prevent pancreatic cancer.
"With these results, I certainly wouldn't say everyone should be taking COX-2 inhibitors to protect against cancer,"ť said Eibl. "However, with additional studies, we may find COX-2 inhibitors could help prevent pancreatic cancer in high risk populations."ť
"Pancreatic cancer is so deadly because it often goes undetected until it's too late,"ť said Dr. Eibl. "If a patient is at a high-risk for developing pancreatic cancer, a COX-2 inhibitor may offer some protection."ť
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 pancreatic cancer.
American Association for Cancer Research
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.
The UCLA researchers 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 researchers to conclude whether or not nimesulide can delay the onset of or prevent pancreatic cancer.
"With these results, I certainly wouldn't say everyone should be taking COX-2 inhibitors to protect against cancer,"ť said Eibl. "However, with additional studies, we may find COX-2 inhibitors could help prevent pancreatic cancer in high risk populations."ť
"Pancreatic cancer is so deadly because it often goes undetected until it's too late,"ť said Dr. Eibl. "If a patient is at a high-risk for developing pancreatic cancer, a COX-2 inhibitor may offer some protection."ť
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 pancreatic cancer.
American Association for Cancer Research
Pancreatic Cancer Current Events and Pancreatic Cancer News RSSAfrican-Americans with colorectal cancer have poorer outcomes, lower survival rates
New research published in the November issue of the Journal of the American College of Surgeons shows that African-American patients with colorectal cancer are more likely to be diagnosed with advanced disease and are less likely to undergo surgical procedures compared with Caucasians, suggesting that improvements in screening and rates of operation may reduce differences in colorectal cancer outcomes for African-Americans.
Discovery offers potential new pancreatic cancer treatment
Tiny particles that can carry drugs and target cancer cells may offer treatment hope for those suffering with pancreatic cancer. New research to be presented in November at the American Association of Pharmaceutical Scientists (AAPS) Annual Meeting in Los Angeles reveals that tumor-penetrating microparticles (TPM) have been specifically designed to break through hard-to-infiltrate barriers and deliver drugs more effectively and efficiently than the standard form of chemotherapy such as those injected through a vein.
Hepatitis B does not increase risk for pancreatic cancer
A Henry Ford Hospital study found that hepatitis B does not increase the risk for pancreatic cancer - and that only age is a contributing factor.
M. D. Anderson examines use of toad venom in cancer treatment
Huachansu, a Chinese medicine that comes from the dried venom secreted by the skin glands of toads, has tolerable toxicity levels, even at doses eight times those normally administered, and may slow disease progression in some cancer patients, say researchers from The University of Texas M. D. Anderson Cancer Center.
Pancreatic cancer: Researchers find drug that reverses resistance to chemotherapy
For the first time researchers have shown that by inhibiting the action of an enzyme called TAK-1, it is possible to make pancreatic cancer cells sensitive to chemotherapy, opening the way for the development of a new drug to treat the disease.
Endothelin-1 inhibitors in chronic pancreatitis
Fibrosis is a key feature of chronic pancreatitis and pancreatic cancer. The extensive deposition of extracellular matrix proteins fosters the development of an exocrine and endocrine organ insufficiency, and accelerates progression of the tumour.
Autoimmune response can induce pancreatic tumor rejection
Immune responses are capable of killing tumors before they can be directed toward normal body tissue, according to new scientific findings published in Cancer Research, a journal of the American Association for Cancer Research.
MicroRNAs circulating in blood show promise as biomarkers to detect pancreatic cancer
A blood test for small molecules abnormally expressed in pancreatic cancer may be a promising route to early detection of the disease.
Blood-flow metabolism mismatch predicts pancreatic tumor aggressiveness
Researchers from Turku, Finland, have identified a blood-flow glucose consumption mismatch that predicted pancreatic tumor aggressiveness, according to results of a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research.
Taking the Needle's Sting Out of Diabetes
Found in 30% of all human cancer tumors, the Ras protein literally "drives cells crazy," says Prof. Yoel Kloog, the dean of the Faculty of Life Sciences at Tel Aviv University. Prof. Kloog was the first in the world to develop an effective anti-Ras drug against pancreatic cancer, currently in clinical trials.
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