May 1, 2007 When bile duct cancer cells were placed in the liver of animals with bile duct obstruction, they grew more rapidly than identical cells placed in animals without bile duct obstruction. In fact, half of the total liver mass of the rats with bile duct obstruction became replaced by cancer cells within three weeks compared to only 16 percent of that of animals without bile duct obstruction.
Perhaps even more important, the cancers metastized outside the liver (as they frequently do in human patients with advanced bile duct cancer) only in the animals with bile duct obstruction.
Virginia Commonwealth University scientist Dr. Alphonse Sirica presented the findings at Experimental Biology 2007 in Washington, DC. His presentation, on April 29, is part of the scientific program of the American Society for Investigative Pathology.
The bile ducts are tubes that carry bile (a liquid secreted by the liver that contains cholesterol, bile salts, and waste products) from the liver to the gallbladder and small intestine. Bile duct obstruction has long been known to be present in both malignant and nonmalignant liver disease (jaundice, for example), but before the study by Dr. Sirica and his colleagues the direct effect of such obstruction on bile duct cancer cell growth and aggressiveness had not been previously investigated.
These new findings are highly significant for two reasons, says Dr. Sirica.
First, they establish an important correlation between bile duct obstruction and bile duct cancer, suggesting growth regulatory mechanisms that could be highly significant in the progression of the cancer and that could become good molecular targets for drug therapy.
Second, they establish a unique preclinical model of how bile duct cancer in liver progresses that can be used to rapidly test and evaluate novel molecular treatment strategies.
Such strategies are badly needed for this understudied cancer, adds Dr. Sirica. The incidence and mortality of cholangiocarcinoma, the primary cancer of the bile ducts, is increasing worldwide. Some 3,500 new cases are now diagnosed annually in the United States. Survival rates remain dismally low because most patients have advanced disease at the time of diagnosis and thus are poor candidates for the current best treatment, surgical resection. Although there are some known risk factors for the disease (such as primary sclerosing cholangitis), the cause of most cases remain unknown and the cellular and molecular changes that accompany the disease have not been well understood.
This study is part of ongoing work in Dr. Sirica's laboratory aimed at identifying altered growth factor signaling pathways in cholangiocarcinoma that may be exploited as potential molecular targets for therapy. Dr. Sirica's co-authors for the Experimental Biology 2007 presentation are Dr. Zichen Zhang, Dr. Toru Asano, Dr. Xue-Ning Shen, Deanna J. Ward and Dr. Arvind Mahatme. Support for the work came from the National Cancer Institute, National Institutes of Health.
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