title: Gene expression analysis in chronic postradiation proctopathy.
abstract: OBJECTIVE
  Radiotherapy is one of the important treatment modalities for tumors of pelvic organs. The fixed location of the rectum and its anatomic relationship with other pelvic organs makes it prone to radiation injury resulting in chronic radiation proctopathy in 5% to 20% of patients. Endothelial dysfunction has been associated with a number of pathophysiological processes. Endothelial cells synthesize and release various factors that regulate angiogenesis, inflammatory responses, hemostasis, as well as vascular tone and permeability.
  
  
  METHODS
  Rectum tissue samples from 20 patients with established chronic radiation proctopathy were analysed for the expression of genes related to oxidative stress, tissue hypoxia, angiogenesis, and inflammation [endoglin (ENG), activin receptor-like kinase 1 (ALK1), platelet endothelial cell adhesion molecule 1 (PECAM), vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), hypoxia-inducible factor 1 (HIF-1), and interleukin-1 beta (IL-1β)].
  
  
  RESULTS
  Overexpression of HIF-1, VEGF, FGF2, and IL-1β was detected in affected tissue. For the first time, a significant suppression of activin receptor-like kinase 1 and ENG could be revealed.
  
  
  CONCLUSIONS
  The data provided here allow further insight into the pathogenesis of radiation-induced rectum injury. Radiation-induced damage is not confined to a single event but involves complex signaling between different pathways, enhancing and maintaining the processes that lead to mucosal damage. The results indicate that postradiation tissue hypoxia is critical for fibrosis, which involves changes in the expression of profibrotic and angiogenic factors in rectal tissue.
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany. Frank-Traub@gmx.net
authors.forename: F
authors.initials: F
authors.lastname: Traub
authors.forename: S
authors.initials: S
authors.lastname: Schleicher
authors.forename: A
authors.initials: A
authors.lastname: Kirschniak
authors.forename: D
authors.initials: D
authors.lastname: Zieker
authors.forename: S
authors.initials: S
authors.lastname: Kupka
authors.forename: M
authors.initials: M
authors.lastname: Weinmann
authors.forename: A
authors.initials: A
authors.lastname: Königsrainer
authors.forename: T
authors.initials: T
authors.lastname: Kratt
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics / Q000378:metabolism; D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000071063:Endoglin; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011878:Radiotherapy / Q000009:adverse effects*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D012002:Rectal Diseases / Q000209:etiology* / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D051793:Hypoxia-Inducible Factor 1; D053583:Interleukin-1beta; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II