hypoxia-inducible factors activate CD133 promoter through ETS family transcription factors.

CD133 is a cellular surface protein that has been reported to be a cancer stem cell marker, and thus it is considered to be a potential target for cancer treatment. However, the mechanism regulating CD133 expression is not yet understood. In this study, we analyzed the activity of five putative promoters (P1-P5) of CD133 in human embryonic kidney (HEK) 293 cells and colon cancer cell line WiDr, and found that the activity of promoters, particularly of P5, is elevated by overexpression of hypoxia-inducible factors (HIF-1α and HIF-2α). Deletion and mutation analysis identified one of the two E-twenty six (ETS) binding sites (EBSs) in the P5 region as being essential for its promoter activity induced by HIF-1α and HIF-2α. In addition, a chromatin imunoprecipitation assay demonstrated that HIF-1α and HIF-2α bind to the proximal P5 promoter at the EBSs. The immunoprecipitation assay showed that HIF-1α physically interacts with Elk1; however, HIF-2α did not bind to Elk1 or ETS1. Furthermore, knockdown of both HIF-1α and HIF-2α resulted in a reduction of CD133 expression in WiDr. Taken together, our results revealed that HIF-1α and HIF-2α activate CD133 promoter through ETS proteins.

Long-term treatment of localized gastric marginal zone B-cell mucosa associated lymphoid tissue lymphoma including incidence of metachronous gastric cancer.

BACKGROUND AND AIM: According to a few recent reports on the long-term clinical outcome of gastric marginal zone B-cell mucosa associated lymphoid tissue lymphoma (MALT lymphoma); localized gastric MALT lymphoma generally has a favorable prognosis. However, the risk of metachronous gastric cancer has not been evaluated. In this study, we analyzed long-term outcomes of localized gastric MALT lymphoma including the incidence of metachronous gastric cancer. METHODS: Between April 1996 and May 2008, 60 patients (31 men and 29 women; mean age 58.1 years) with localized gastric MALT lymphoma (stage I and II(1) according to Lugano classification) were analyzed retrospectively. RESULTS: Forty-eight patients (82.6%) achieved complete remission by eradication therapy. Radiation therapy was conducted on eight patients as second-line treatment, and all of them achieved remission. The median follow-up period was 76 months (range, 12-157 months). One patient had local relapse after remission for 5 years and three patients developed early gastric cancer without recurrence of lymphoma (5%). All of the three gastric cancers appeared in the same areas where MALT lymphoma had been eradicated. CONCLUSION: Eradication therapy and radiation therapy for localized gastric MALT lymphoma have a favorable long-term outcome, though regular follow-up endoscopy should be performed for detecting metachronous early gastric cancer.

Preliminary trial of rebamipide for prevention of low-dose aspirin-induced gastric injury in healthy subjects: a randomized, double-blind, placebo-controlled, cross-over study.

Although low-dose aspirin is widely used, since it is a cheap and effective means of prevention of cardiovascular events, it can cause hemorrhagic gastrointestinal complications. The aim of this study was to evaluate the efficacy of rebamipide in preventing low-dose aspirin-induced gastric injury. A randomized, double-blind, placebo-controlled, crossover trial was performed in twenty healthy volunteers. Aspirin 81 mg was administered with placebo or rebamipide 300 mg three times daily for 7 consecutive days. The rebamipide group exhibited significant prevention of erythema in the antrum compared with the placebo group (p = 0.0393, respectively). Results for the body and fornix did not differ significantly between the placebo and rebamipide groups. In conclusion, short-term administration of low-dose aspirin induced slight gastric mucosal injury in the antrum, but not in the body or fornix. Rebamipide may be useful for preventing low-dose aspirin-induced gastric mucosal injury, especially which confined to the antrum.