title: Neuromuscular electrical stimulation improves radiation-induced fibrosis through Tgf-Β1/MyoD homeostasis in head and neck cancer.
abstract: OBJECTIVE
  The purpose of this study was to analyze TGF-β1 and MyoD expression in cervical muscles during radiation therapy (RT) and their role in inducing muscle fibrosis in head and neck cancer (HNC) patients. We also studied the effect of combined traditional swallow therapy (TST) and neuromuscular electrical stimulation (NMES) therapy on TGF-β1/MyoD homeostasis in patients undergoing post-operative RT for HNC.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Thirty patients, 10 with benign thyroid lesions and non-radiated muscle (control), and 20 with advanced-stage HNC receiving primary resection and post-operative radiation (study group) were enrolled. Patients in the study group were randomly assigned to receive post-operative RT alone (Group I) or post-operative RT with TST/NMES therapy (Group II). Intraoperative biopsies were obtained in all 30 patients. In the study groups, biopsies were repeated 4 weeks after completion of RT. TGF-β1 and MyoD expression were evaluated by immunohistochemistry and Western Blot.
  
  
  RESULTS
  The control group demonstrated low expression of TGF-β1 and high expression of MyoD. Following RT, patients in study Group I had high expression of TGF-β1 and low levels of MyoD. Group II patients demonstrated TGF-β1 levels more consistent with that of non-irradiated tissue.
  
  
  CONCLUSIONS
  The molecular pathogenesis of RT-induced muscle fibrosis involves the TGF-β1 pathway and its repression of MyoD expression. Our results suggest a correlation between TST/NMES combined therapy and the restoration of TGF-β1/MyoD homeostasis in cervical muscles. TST/NMES is a plausible prophylaxis and/or treatment for RT-induced muscle fibrosis and dysphagia. J. Surg. Oncol. 2016;114:27-31. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, California.
authors.forename: Grace
authors.initials: G
authors.lastname: Peng
authors.affiliation: Department of Public Health, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Kamil
authors.initials: K
authors.lastname: Masood
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, California.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gantz
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, California.
authors.forename: Uttam
authors.initials: U
authors.lastname: Sinha
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy* / Q000601:surgery; D016022:Case-Control Studies; D004599:Electric Stimulation Therapy; D005355:Fibrosis; D006258:Head and Neck Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D006706:Homeostasis; D006801:Humans; D007150:Immunohistochemistry; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects*; D017570:MyoD Protein / Q000378:metabolism*; D011832:Radiation Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D000077195:Squamous Cell Carcinoma of Head and Neck; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D017570:MyoD Protein; D053773:Transforming Growth Factor beta1
keywords: Myo-D; head and neck cancer; neuromuscular electrical stimulation therapy (NMES); radiation therapy (RT); traditional swallow therapy (TST); transforming growth factor beta (TGF-β)