title: The neutrophil elastase inhibitor sivelestat suppresses accelerated gastrointestinal tumor growth via peritonitis after cecal ligation and puncture.
abstract: BACKGROUND
  We examined whether tumor growth is enhanced by cecal ligation and puncture (CLP) and suppressed by a neutrophil elastase inhibitor, sivelestat.
  
  
  METHODS
  C57BL/6 mice were divided in CLP/sivelestat, CLP alone, and control (simple laparotomy) groups. Murine CT26 colon carcinoma cells were injected subcutaneously into the back of each mouse and tumor growth and serum cytokine levels were assessed.
  
  
  RESULTS
  Mice subjected to CLP alone exhibited enhanced tumor growth compared to controls with subcutaneously injected CT26 cells (0.64±0.24 g vs. 0.021±0.027 g, p<0.001), while treatment with CLP/sivelestat produced smaller tumors than CLP alone (0.28±0.23 g vs. 0.64±0.24 g, p=0.006). Cytokine assays showed suppressed production of interleukin (IL)-6 and IL-10 in the CLP/sivelestat group, and increased IL-6 and IL-10 in the CLP-alone group.
  
  
  CONCLUSIONS
  Intra-abdominal inflammation induced by CLP enhances the growth of subcutaneously implanted tumors, while perioperative administration of sivelestat suppresses tumor growth by affecting systemic inflammation.
authors.affiliation: Department of Surgery, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. saiky@z8.keio.jp.
authors.forename: Koshi
authors.initials: K
authors.lastname: Kumagai
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saikawa
authors.forename: Hiroya
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Koichi
authors.initials: K
authors.lastname: Suda
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Fukuda
authors.forename: Rieko
authors.initials: R
authors.lastname: Nakamura
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Takahashi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kawakubo
authors.forename: Norihito
authors.initials: N
authors.lastname: Wada
authors.forename: Taku
authors.initials: T
authors.lastname: Miyasho
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D000818:Animals; D002432:Cecum / Q000601:surgery*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D005770:Gastrointestinal Neoplasms / Q000150:complications / Q000473:pathology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008026:Ligation; D051379:Mice; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000150:complications* / Q000209:etiology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D019272:Leukocyte Elastase; D005998:Glycine
keywords: CT26 murine colon cancer; cecal ligation and puncture; compensatory anti-inflammatory response syndrome; neutrophil elastase inhibitor; sivelestat