R420 – Radiation Induces TGF-β and Blocks MyoD Causing Fibrosis

Abstract

Problem One of the main treatment modalities for head and neck cancer (HNC) is post-operative radiation therapy (RT). Patients undergoing RT develop dysphagia due not only to salivary gland damage, but also scarring of the pharyngeal and strap musculature. We have compared the levels of TGF-β in the strap muscle samples in patients at the beginning and end of their RT and found that TGF-β may contribute to excessive fibrosis by blocking MyoD expression, a gene necessary in muscle differentiation and repair. A second part of this study views the effects of concurrent transcutaneous neuromuscular electrical stimulation (NMES) during RT on TGF-β and MyoD levels. Our objective is to examine not only the effects muscle repair post-radiation, but also to view the effects of electrical stimulation during concurrent radiation therapy on the expression of TGF-β and MyoD. Methods We used muscle samples from patients of various stages of HNC pre-radiation and post-radiation, with some receiving NMES during RT. The TGF-β and MyoD expression were measured using western blotting and immunohistochemistry staining. Results TGF-β expression was higher in all samples post RT as compared to non-radiated controls. In addition, there is decreased fibrosis seen in patients who have undergone RT and concurrent NMES as compared to patients who underwent RT alone. We also observed that those patient specimens with higher TGF-β showed lower expression of MyoD than patients with lower TGF-β expression. Conclusion RT induced higher TGF-β which blocked MyoD expression and muscle differentiation, inducing fibrosis. We hope to study different techniques of electrical stimulation during patients' RT in order to optimize the stimulation. Significance Understanding the mechanism through fibrosis develops can help us to increase the quality of life of patients who successfully undergo cancer research and eradication with radiation therapy. Practicing transcutaneous NMES can help to decrease the dysphagia seen in patients using RT.