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UC Davis researchers discover Achilles' heel in pancreatic cancer
Date:11/6/2008

reatic cell lines that represent the varying levels of argininosuccinate synthetase observed in human tumor specimens. Focusing on the lines with lowest levels, the researchers depleted arginine levels in cultures of pancreatic cell lines using arginine deiminase, an enzyme isolated from a Mycoplasma bacteria.

The enzyme was modified by adding polyethylene glycol chains to increase size and circulatory time.

The researchers found that exposing the pancreatic cancer cell lines to the modified arginine deiminase enzyme inhibited cancer-cell proliferation by 50 percent. They then treated mice bearing pancreatic tumors with the same compound and found an identical outcome: a 50 percent reduction in tumor growth. According to Bold, the current study represents a unique approach to cancer treatment in that it is one of the first to identify a metabolic pathway that can be leveraged to interrupt cancer growth.

"Instead of killing cells as with typical chemotherapy, we instead removed one of the key building blocks that cancer cells need to function," Bold said.

Metabolic interruptions like this one are also being studied for their potential in treating cancers of the blood, such as leukemia and lymphoma. In those cases, depleting the amino acid asparagine may be used in slowing cancer-cell growth.

Bold and his colleagues are continuing their laboratory work on the effects of arginine deprivation on pancreatic cancer. They will next be looking for ways to increase pancreatic cell sensitivity to arginine deprivation.

The researchers have also begun designing human clinical trials in cooperation with the manufacturer of arginine deiminase, Polaris Pharmaceuticals.

"We're looking at whether we can combine this treatment with certain kinds of chemotherapy," Bold said. "This additional research is needed to inform the clinical work and move it forward more quickly. The better we understand this process, the more we c
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Contact: Karen Finney
karen.finney@ucdmc.ucdavis.edu
916-734-9064
University of California - Davis - Health System
Source:Eurekalert

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