title: Topical application of acetic acid in cytoreduction of gastric cancer. A technical report using mouse model.
abstract: OBJECTIVE
  Application of acetic acid topically to the mucosal or serosal side of the stomach has been well used to create a chronic gastric ulcer model. The aim of the present study was to apply it as a new cytoreductive approach in a mouse model of gastric cancer.
  
  
  METHODS
  A total of 43 genetically engineered mice, the so-called (INS-GAS) mice that develop spontaneously gastric cancer at 10-14 months of age, were included. Acetic acid-induced ulcer method was applied to mice under isofluran anesthesia. The ulcer at the cancer side was made by exposing either the anterior serosal or posterior mucosal side of gastric wall to 0.1 mL of 60% or 100% acetic acid for 30 or 60 s with a cylindrical metal mold (4 mm ID). Route to the serosal side was intra-abdominal and one to the mucosal side was through a small hole made in the forestomach. The opposite side of gastric wall (no treatment with acetic acid) was used as the corresponding control. After the mice were sacrificed, the stomachs were collected 1, 3, 6 h or 1, 3 and 7 days, postoperatively, and evaluated by visual inspection and histology.
  
  
  RESULTS
  Gastric cancer was found in both the anterior and posterior walls of the corpus in all 43 mice. Intraluminal pH value was between 11 and 13. Severe necrosis in the cancer was observed in the side exposing to acetic acid, but not in the control side, shortly after the treatment (i.e. within 30 or 60 min). The muscularis mucosa and muscle layers were less damaged, regardless of the side of the treatment. Ulcer formation in the cancer took place 1, 3 or 7 days later. The ulcer depth was sometimes at the muscularis mucosa and muscle layers. At 3 and 7 days, regeneration of epithelial cells was clearly observed in the ulcer margin in the stomach of mice.
  
  
  CONCLUSIONS
  Topical application of acetic acid either from mucosal or serosal surface promptly caused the necrosis of tumor, suggesting the potential approach of this simple and reliable method as a cytoreductive treatment of gastric cancer in patients through endoscopy or laparoscopy.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. okabe1422@nifty.com
authors.forename: Susumu
authors.initials: S
authors.lastname: Okabe
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kodama
authors.forename: Hailong
authors.initials: H
authors.lastname: Cao
authors.forename: Helene
authors.initials: H
authors.lastname: Johannessen
authors.forename: Helenne
authors.initials: H
authors.lastname: Johannessen
authors.forename: Chun Mei
authors.initials: CM
authors.lastname: Zhao
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wang
authors.forename: Rei
authors.initials: R
authors.lastname: Takahashi
authors.forename: Duan
authors.initials: D
authors.lastname: Chen
mesh_terms: D019342:Acetic Acid / Q000008:administration & dosage* / Q000633:toxicity; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000287:Administration, Topical; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D009336:Necrosis; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D019342:Acetic Acid