In addition to eradication of Helicobacter pylori, chemotherapy with anticancer agents, and radiation therapy, the treatment
with molecular target drugs including rituximab, a CD20 antagonist, is one of the promising new regimens. The mucosa-associated lymphoid
tissue (MALT) lymphoma is histologically characterized by rich distribution of the microvascular network consisting of the immature
capillaries, lymphatics and venules, and this microvascular network could be the target of the new pharmacotherapy in addition to
the direct action on the accumulated B lymphocytes. We have established the animal model of the gastric MALT lymphoma by
the Helicobacter heilmannii (H. heilmannii) peroral infection of C57BL/6 mice. The disease induced by this model is very similar to the
human counterpart, because of the lymphoepithelial lesion characteristic of the human MALT lymphoma as well as the rich vascularization
and localization of vascular endothelial growth factor (VEGF) and its receptors, Flt-1, Flk-1 and Flt-4. By administering VEGF receptor
antibodies or celecoxib, one of the cyclooxygenase 2 inhibitors, we were able to induce a significant decrease in the size of the
tumor and the apoptotic changes of the endothelial cells of the microvascular network. These antiangiogenic strategies were suggested to
be candidates for the new pharmacological treatment of gastric MALT lymphoma, when other treatments are not effective.
Keywords: Gastric MALT lymphoma, angiogenesis, lymphangiogenesis, VEGF, Flt-1, Flk-1, Flt-4, celecoxib.
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