Nonsteroidal antiinflammatories are known to suppress incidence and progression of malignancies including colorectal cancers. However, the precise mechanism of this action remains unknown. Using prostaglandin (PG) receptor knockout mice, we have evaluated a role of PGs in tumor-associated angiogenesis and tumor growth, and identified PG receptors involved. Sarcoma-180 cells implanted in wild-type (WT) mice formed a tumor with extensive angiogenesis, which was greatly suppressed by specific inhibitors for cyclooxygenase (COX)-2 but not for COX-1. Angiogenesis in sponge implantation model, which can mimic tumor-stromal angiogenesis, was markedly suppressed in mice lacking EP3 (EP3−/−) with reduced expression of vascular endothelial growth factor (VEGF) around the sponge implants. Further, implanted tumor growth (sarcoma-180, Lewis lung carcinoma) was markedly suppressed in EP3−/−, in which tumor-associated angiogenesis was also reduced. Immunohistochemical analysis revealed that major VEGF-expressing cells in the stroma were CD3/Mac-1 double-negative fibroblasts, and that VEGF-expression in the stroma was markedly reduced in EP3−/−, compared with WT. Application of an EP3 receptor antagonist inhibited tumor growth and angiogenesis in WT, but not in EP3−/−. These results demonstrate significance of host stromal PGE2-EP3 receptor signaling in tumor development and angiogenesis. An EP3 receptor antagonist may be a candidate of chemopreventive agents effective for malignant tumors.
The effect of electrolyzed water on total microbial count was evaluated on several fresh-cut vegetables. When fresh-cut carrots, bell peppers, spinach, Japanese radish, and potatoes were treated with electrolyzed water (pH 6.8, 20 ppm available chlorine) by dipping, rinsing, or dipping/blowing, microbes on all cuts were reduced by 0.6 to 2.6 logs CFU/g. Rinsing or dipping/blowing were more effective than dipping. Electrolyzed water containing 50 ppm available chlorine had a stronger bactericidal effect than that containing 15 or 30 ppm chlorine for fresh-cut carrots, spinach, or cucumber. Electrolyzed water did not affect tissue pH, surface color, or general appearance of fresh-cut vegetables.
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