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Tumor cells made more sensitive to radiation by blocking a key cellular molecule

In recent years, cancer researchers have sought ways to make tumors more receptive to treatment. In a series of novel experiments, scientists at the University of North Carolina at Chapel Hill have succeeded in making tumor cells more sensitive to destruction by radiation therapy.

This was accomplished in colorectal tumor cells by two experimental interventions aimed at blocking activation of a cellular protein, NF-kappaB.

The findings will be detailed in Boston, Wednesday, October 25, at the annual meeting of the American Society for Therapeutic Radiation and Oncology.

Earlier research has shown that activation of the molecule in some tumor types inhibits the cellular self-destruction process called apoptosis. Moreover, ionizing radiation, which is used against malignancies, and some anti-cancer drugs, also may induce NF-kappaB activation.

"This can reduce the cell-killing effects of chemotherapy or radiation," said Joel E. Tepper, MD, head of radiation oncology at UNC-CH School of Medicine and a member of UNC Lineberger Comprehensive Cancer Center. "But it's also known you can inhibit the inhibition of apoptosis. And if you can do that, you may be able to do a more effective job of killing tumor cells with standard anticancer therapies."

The UNC experiments were aimed at determining if the effects of radiation would be enhanced against tumor cells in which NF-kappaB activation was inhibited. Suzanne M. Russo, MD, a former radiation oncology resident at UNC, and now a radiation oncologist at Wake Forest University led the study. Collaborators included Tepper and other Lineberger Center members Albert S. Baldwin, PhD, and James C. Cusack, MD.

The team investigated colorectal tumor cells in lab dishes and in tumors grown on mice. In carefully controlled experiments, they studied two methods of inhibiting NF-kappaB activation. One is the experimental drug PS-341, a proteosome inhibitor chemical that prevents the cell from degrading or
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Contact: Leslie H. Lang
LLANG@MED.UNC.EDU
919-843-9687
University of North Carolina School of Medicine
24-Oct-2000


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