title: EW-7197, an activin-like kinase 5 inhibitor, suppresses granulation tissue after stent placement in rat esophagus.
abstract: OBJECTIVE
  Self-expanding metallic stent (SEMS) placement is a well-established method for treating malignant esophageal strictures; however, this procedure has not gained widespread acceptance for treating benign esophageal strictures because of granulation tissue formation. The aim of the present study was to investigate whether EW-7197, a novel per-oral transforming growth factor-β type I receptor kinase inhibitor, suppressed granulation tissue formation after SEMS placement in the rat esophagus.
  
  
  METHODS
  Sixty rats underwent SEMS placement and were randomly divided into 4 groups. Group A (n = 20) received vehicle-treated control for 4 weeks. Group B (n = 20) received 20 mg/kg/day EW-7197 for 4 weeks. Group C (n = 10) received 20 mg/kg/day EW-7197 for 4 weeks followed by vehicle-treated control for 4 weeks. Group D (n = 10) received 20 mg/kg/day EW-7197 for 8 weeks.
  
  
  RESULTS
  SEMS placement was technically successful in all rats. Eleven rats, however, were excluded because of stent migration (n = 9) and procedure-related death (n = 2). The luminal diameter in group A was significantly smaller than those in groups B, C, and D (all P < .001). The percentage of granulation tissue area, number of epithelial layers, thickness of submucosal fibrosis, percentage of connective tissue area, and degree of collagen deposition were significantly higher in group A than in groups B, C, and D (all P < .001); however, there were no significant differences among groups B, C, and D. EW-7197 decreased the expression levels of phospho-Smad 3, N-cadherin, fibronectin, α-smooth muscle actin, and transforming growth factor-β1 and increased the expression level of E-cadherin (all P < .01).
  
  
  CONCLUSIONS
  EW-7197 suppressed granulation tissue formation after SEMS placement in the rat esophagus.
authors.affiliation: Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Jun
authors.affiliation: Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Biomedical Engineering Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Jiaywei
authors.initials: J
authors.lastname: Tsauo
authors.affiliation: Department of New Drug Development and NCEED, School of Medicine, Inha University, Incheon, Republic of Korea.
authors.forename: Su-Geun
authors.initials: SG
authors.lastname: Yang
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Women's University, Seoul, Republic of Korea.
authors.forename: Dae-Kee
authors.initials: DK
authors.lastname: Kim
authors.affiliation: Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Kun Yung
authors.initials: KY
authors.lastname: Kim
authors.affiliation: Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Min Tae
authors.initials: MT
authors.lastname: Kim
authors.affiliation: Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Yoon
authors.affiliation: Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Young Je
authors.initials: YJ
authors.lastname: Lim
authors.affiliation: Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Ho-Young
authors.initials: HY
authors.lastname: Song
mesh_terms: D000199:Actins / Q000378:metabolism; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D004947:Esophagus / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism; D006097:Granulation Tissue / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D000069322:Self Expandable Metallic Stents / Q000009:adverse effects*; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000199:Actins; D000814:Aniline Compounds; D015820:Cadherins; D005353:Fibronectins; D009419:Nerve Tissue Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D014230:Triazoles; C000610228:CDH1 protein, rat; C570099:N-cadherin, rat; C497787:Smad3 protein, rat; C000590371:vactosertib; C000625843:Tgfbr1 protein, rat; C498862:Acta2 protein, rat