Helicobacter Felis Eradication Restores Normal Architecture and Inhibits Gastric Cancer Progression in C57BL/6 Mice

Gastroenterology. 2005 Jun;128(7):1937-52. doi: 10.1053/j.gastro.2005.02.066.

Abstract

Background & aims: The impact of Helicobacter eradication therapy on the progression or regression of gastric lesions is poorly defined. This study examined the effects of eradication therapy on inflammation, atrophy, metaplasia, dysplasia, and cancer progression.

Methods: C57BL/6 mice were infected with Helicobacter felis and received bacterial eradication therapy after 2, 6, or 12 months of infection. The gastric mucosa was examined at early, mid, and late intervals after eradication and graded for histology, expression pattern of alpha-catenin and beta-catenin, and IQGAP1.

Results: Eradication of Helicobacter infection after 2 or 6 months of infection led to a regression of inflammation, restoration of parietal cell mass, and reestablishment of normal architecture. Progression to adenocarcinoma was prevented. Bacterial eradication at 1 year was associated with the reappearance of parietal cells, partial regression of inflammation, and restoration of architecture. Hyperplasia scores significantly improved, and dysplasia did not progress. Infected mice developed antral adenocarcinoma and gastric outlet obstruction by 24 months. Only 30% of the mice receiving bacterial eradication therapy at 12 months developed antral carcinoma. Bacterial eradication at any time during the first year of infection prevented death due to gastric outlet obstruction. The expression pattern of alpha-catenin, beta-catenin, and IQGAP1 varied with cell type and paralleled histologic changes.

Conclusions: Inflammation, metaplasia, and dysplasia are reversible with early eradication therapy; progression of dysplasia was arrested with eradication therapy given as late as 1 year and prevented gastric cancer-related deaths.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / microbiology*
  • Adenocarcinoma / prevention & control
  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Atrophy
  • Disease Models, Animal
  • Gastric Mucosa / immunology
  • Gastric Mucosa / pathology
  • Helicobacter Infections / complications
  • Helicobacter Infections / drug therapy*
  • Helicobacter felis / pathogenicity*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Precancerous Conditions / microbiology*
  • Precancerous Conditions / pathology
  • Stomach Neoplasms / microbiology*
  • Stomach Neoplasms / prevention & control
  • Tetracycline / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Tetracycline