Studies on Helicobacter species on gastric MALT lymphoma and effect of molecular target drugs

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By the investigation of the specimens obtained from the upper gastrointestinal endoscopy of the patients suffering from chronic gastritis, gastric ulcer, gastric polyp, gastric cancer and gastric MALT lymphoma, 7 MALT lymphoma cases out of 18 (38%) were found to be positive to Helicobacter heilmannii, while only 2% were positive in other gastric diseases. By the cluster analysis using GENENTYC-MAC UPGMA, these cases were found to be infected by Helicobacter heilmannii and suis. Among other gastric diseases, nodular gastritis patents were found to be highly positive to H. heilmannii, suggesting the possible interaction with the gastric cancer. In H. heilmannii positive cases, more than half cases were found to show the positivity to H. pylori as well.By the in vivo study using the infection model using C57BL/6 mice, VEGF-related immunoreactities were recognized in the MALT lymphoma, suggesting the VEGF-mediated angiogenesis was closely related to the expansion of the tumor. The administration of Flt-4 and Flt-1 antibody suppressed the tumor, supporting this hypothesis. c-Met immunoreactivity was found in the lymphocytes composing the MALT lymphoma, and HGF immunoreactivity was recognized mostly in the endothelial cells and macrophages. HGFA was localized on mesenchymal cells other than the lymphocytes. The administration of antibodies against c-Met to the infected mice induced the significant suppression of hepatic and pulmonary lesions as well as the gastric MALT lymphoma.In conclusion, HGF and c-Met pathway were suggested to contribute to the lymphomagenesis in the liver and lung after Helicobacter heilmannii infection.