ABSTRACT
Understanding the role and mechanism of signaling pathways including Notch and Wnt in colorectal carcinogenesis is critical to the development of novel therapeutics. In the present study, we analyzed the cell proliferation, migration, G2/M percentage and the expression of molecules of signaling pathways in HCT-116 cells through the inhibition of Wnt and Notch pathways, and also investigated the effect of inhibitors of Wnt and Notch pathways on tumor growth in a transplantation tumor model. We observed that rDDK-1 (an inhibitor of the Wnt signaling pathway) and LY374973 (an inhibitor of the Notch signaling pathway) synergistically inhibited the proliferation, migration and G2/M percentage of HCT-116 cell lines, and could further synergistically inhibit the tumor volume and weight in the transplantation tumor model. In the cell line and the transplantation tumor model, rDDK-1 and LY374973 further synergistically inhibited the expression level of all detected Wnt and Notch pathway genes. Our results may pave the way for using inhibitors of Wnt and Notch signaling pathways together to treat colorectal cancer.
ABSTRACT
BACKGROUND: There is no study of circumferential EMR in patients with Barrett's esophagus containing early stage malignant lesions. This study investigated the effectiveness and safety of circumferential EMR by using a simple snare technique without cap. METHOD: Patients with Barrett's esophagus containing multifocal high-grade intraepithelial neoplasia or intramucosal cancer, and patients with endoscopically nonidentifiable early stage malignant mucosal changes incidentally detected in random biopsy specimens were included in the study. A 30 x 50-mm polypectomy snare made of monofilament 0.4-mm steel wire was used without any additional device or submucosal injection. RESULTS: Twelve patients (10 men, 2 women; median age 63.5 years, range 43-88 years) underwent circumferential EMR; 5 had multifocal lesions, and 7 had no visible lesions. Segments of Barrett's epithelium were circumferential (median length 5 cm) and completely removed. The median number of EMR sessions was 2.5. The median number of snare resections per EMR session was 5. The medial total area of mucosa in resected specimens per session was 3.8 cm(2). Two patients developed strictures that were successfully treated by bougienage. Minor bleeding occurred during 4 of 31 EMR sessions. During a median follow-up of 9 months, no recurrence of Barrett's esophagus or malignancy was observed. CONCLUSIONS: Circumferential EMR with a simple snare technique is feasible, safe, and effective for complete removal of Barrett's epithelium with early stage malignant changes.
