Morimasa Tomikawa

Activation of VEGF and Ras genes in gastric mucosa during angiogenic response to ethanol injury

Our previous studies demonstrated that ethanol injury triggers the angiogenic response in gastric mucosa bordering necrosis. The present study was aimed to determine whether vascular endothelial growth factor (VEGF) (a potent angiogenic peptide selectively acting on endothelial cells) and Ras (a mediator of cell proliferation and a putative regulator of VEGF expression) are involved in gastric angiogenesis after ethanol injury. We studied the angiogenic response and expression of VEGF and Ras in gastric mucosa after ethanol injury. Ethanol damage triggered 1) angiogenesis in the gastric mucosa bordering necrosis, 2) significant increases in VEGF mRNA and protein expression, and 3) significant increases in the expression of Ki-ras mRNA and Ras proteins. Neutralizing anti-VEGF antibody significantly reduced (by greater than threefold) the angiogenic response to ethanol-induced injury. Moreover, mevastatin, an inhibitor of Ras activation, completely blocked the induction of VEGF expression in cultured primary endothelial cells. Because, in other tissues, VEGF is one of the most potent angiogenic factors and VEGF expression is dependent on Ras, our data indicate that Ras and VEGF are involved in gastric mucosal angiogenesis after ethanol injury.

Overview of Endoscopic Injection Sclerotherapy in 1200 Patients with Esophageal Varices

Endoscopic injection sclerotherapy is the treatment of choice worldwide for actively bleeding esophageal varices [1]. Long-term, repeated sclerotherapy eradicates varices in most patients and reduces the rate of subsequent hemorrhage. However, in recent prospective randomized trials, the frequency of episodes of bleeding was significantly greater among patients undergoing variceal sclerotherapy and mortality did not differ in the two study and control groups [2, 3]. The differences in those studies seem to be due to the different techniques used and to the follow-up system.