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

通过对慢性胃炎、胃溃疡、胃息肉、胃癌和胃MALT淋巴瘤患者的上消化道内镜标本的调查，18例MALT淋巴瘤患者中有7例（38%）发现海门螺杆菌阳性，而其他胃疾病患者中只有2%呈阳性。GENENTYC-MAC UPGMA聚类分析表明，这些病例感染了人类幽门螺杆菌和猪幽门螺杆菌。在其他胃疾病中，结节性胃炎患者对heilmannii高度阳性，提示可能与胃癌相互作用。在海门螺杆菌阳性的病例中，超过一半的病例也显示幽门螺杆菌阳性。通过C57BL/6小鼠感染模型的体内研究，在MALT淋巴瘤中发现了vegf相关免疫反应，提示vegf介导的血管生成与肿瘤的扩张密切相关。Flt-4和Flt-1抗体的使用抑制了肿瘤，支持了这一假设。c-Met免疫反应性主要见于MALT淋巴瘤的淋巴细胞，HGF免疫反应性主要见于内皮细胞和巨噬细胞。HGFA定位于间充质细胞而非淋巴细胞。对感染小鼠给予c-Met抗体可显著抑制肝脏和肺部病变以及胃MALT淋巴瘤。综上所述，HGF和c-Met途径参与了海门螺杆菌感染后肝脏和肺部的淋巴瘤形成。

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.