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Anti-integrin antibody inhibits radiation-induced lung fibrosis

Anti-integrin antibody inhibits radiation-induced lung fibrosis

LOS ANGELES—New drugs on the horizon could reduce the adverse effects of radiation to the lung, allowing higher doses for lung cancer patients, according to studies presented at the 49th ASTRO annual meeting.

In studies at New York University, mice given radiation to the lungs had a sharply reduced incidence of radiation-induced fibrosis when treated with an antibody to integrin-b-6, a molecule central to signaling in the transforming growth factor-beta (TGF-b) pathway (ASTRO plenary abstract 1). [See also article on page 42.]

"Previous research has shown that TGF-b, a potent cytokine that is upregulated after radiation exposure, is an acute mediator of radiation-induced lung injury," commented presenting author Simon K. Cheng, MD, PhD, a resident at the NYU Cancer Institute. He and his colleagues evaluated the role of integrin-b-6, a key activator of TGF-b that has been implicated in fibrosis.

"As seen in our mouse model of radiation-induced fibrosis, integrin-b-6 is strongly upregulated starting 18 weeks postradiation. Then 2 weeks later, the onset of fibrosis can be seen histologically," Dr. Cheng explained.

The investigators, led by John Munger, MD, and Silvia Formenti, MD, of the NYU School of Medicine, first assessed the impact of a single 14-Gy fraction of radiation to the lungs in wild-type mice and in integrin-b-6 knockout mice. Between 24 and 28 weeks after radiation, most wild-type mice had marked alveolar remodeling of the lung relative to their nonirradiated counterparts; in contrast, irradiated knockout mice had essentially normal lung architecture relative to their nonirradiated counterparts.

In addition, the irradiated wild-type mice had a roughly 65% increase in collagen deposition, as assessed by measurement of hydroxyproline, whereas the irradiated knockout mice had levels similar to those of nonirradiated knockout mice.

"These results taken together show that integrin-b-6 is required for radiation-induced fibrosis," Dr. Cheng said.

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