Correlation between bile duct obstruction and ductal cancer found

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Public release date: 29-Apr-2007

Federation of

American Societies for Experimental Biology

Correlation

between bile duct obstruction and ductal cancer found

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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