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Denis Guttridge, PhD

Award Name Pilot Grant

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Stem cells a new target in pancreatic cancer cachexia

The Ohio State University Center for Clinical and Translational Science awarded Denis Guttridge, PhD, and his collaborators, Federica Montanaro, PhD; Mark Bloomston, MD; and Pete Muscarella, MD; a pilot grant for their research looking at muscle stem cells as a therapy for muscle wasting in pancreatic cancer patients.

Guttridge and Montanaro started their collaboration several years ago. The researchers hope to determine what happens to muscle stem cells in a weight loss condition called cachexia, which can accompany pancreatic cancer.

Tumors require fuel and energy to grow, and in many cancers they draw energy from the body’s own tissues. Since skeletal muscle tissue is so abundant, tumors target it and break it down for fuel. Thus cancer-induced cachexia results in a depletion of muscle tissue.

Estimates suggest up to one-third of cancer deaths result from cachexia rather than directly from the tumor burden. No effective treatment currently exists for muscle loss related to cachexia.

Based on their previous collaborative studies in animal models, the Guttridge and Montanaro labs believe that cachexia involves a dysfunction of muscle stem cells. The goal of this project is to first develop a technique that allows researchers to isolate human muscle stem cells from pancreatic cancer patients, and then compare them to those previously studied by the group in animal models of cancer-induced cachexia.

Using these findings to develop a treatment for muscle wasting is still a long way off.

“We have an idea now what’s happening in the mouse model that may be a contributing factor in muscle wasting and cancer,” Guttridge said. “But they are mice and they’re different than people.”

By observing human muscle stem cells, Guttridge and Montanaro hope to establish similarities between human and mouse muscle stem cells in cancer-induced cachexia.

“If you can establish commonalities between species, therapies that can be developed in animal models can provide you confidence that it may be translatable to the clinic,” Guttridge said.

Very little is known about human muscle stem cells. A large part of this study will be isolating stem cells for observation and comparing their profiles to those studied in animal models.

“It all comes down to the main goal, which is to be able to capture and observe the cells,” Guttridge said.

Samples for the study are coming from pancreatic cancer patients admitted to the OSU Medical Center who consent to participate.

“I would think that in the next year we’ll start to have some idea of the feasibility of isolating these cells from cancer patients and that can hopefully also provide us with insight on mechanisms that lead to cachexia,” Guttridge said.

By Emily Tramte, Wednesday, June 30, 2010

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