AIM: To study the effect of Lomerizine on the activity of P-glycorprotein (P-gp) in primary cultured rat brain microvessel endothelial cells (RBMECs). METHODS: Flow cytometry was used to study the efflux of rhodamine123 (Rh123) and expression of P-gp in RBMECs. RT-PCR was used to measure the expression in mRNA level of mdr1 gene in RBMECs. Transwell model was used to detect the influence of Lomerizine on the transport of Rh123 through RBMECs monolayer. RESULTS: Lomerizine inhibited the efflux of Rh123 in RBMECs. No changes of P-gp and mdr1 gene mRNA expression were detected in RBMECs after the treatment with 30 μmol·L-1 Lomerizine for 72 h. In the study of Transwell model, Lomerizine increased significantly the transport of Rh123 through RBMECs monolayer from upper compartments to lower compartments, and inhibited obviously the transport in reverse direction. CONCLUTION: The effect of Lomerizine on the activity of P-gp was mainly via its direct inhibitory effect on the function of P-gp in RBMECs and the transport of P-gp substrates in BBB may be affected by lomerizine.

AIM:To evaluate effects of different chemotherapeutic agents on reversing the acquired resistance to TRAIL gene and clarify the involved mechanisms in DLD1-TRAIL/R colon cancer cells.METHODS: Human colon cancer cell line DLD1-TRAIL/R cells that were resistant to TRAIL-expressing adenovector(Ad/gTRAIL) were treated with Ad/gTRAIL combined with different chemotherapeutic agents.Then,the cell viability was measured by MTT method,and apoptotic signaling conditions,including activation of caspase-3 and caspase-8,expression of Bax and Bcl-XL,were measured by Western blotting analysis.RESULTS: In vitro data showed that several chemotherapeutic agents,including 5-fluorouracil(5-FU) and mitomycin c(MMC),overcome the acquired resistance to TRAIL gene in DLD1-TRAIL/R colon cancer cells.The combination of Ad/gTRAIL and 5-FU effectively suppressed tumor growth in vivo in subcutaneous tumors established from DLD1-TRAIL/R cells.Further data showed that treatment with the combination of Ad/gTRAIL and 5-FU or MMC led to enhance the activation of caspase-3.Moreover,MMC but not 5-FU induced overexpression of Bax gene that was sufficient to overcome the resistance to TRAIL gene in DLD1-TRAIL/R cells.CONCLUSION: Chemotherapeutic agents,such as 5-FU and MMC,overcome the acquired resistance to TRAIL gene in DLD1-TRAIL/R cells.The candidate mechanisms for MMC but not 5-FU to overcome this resistance might involve the induction of over-expressed Bax protein in DLD1-TRAIL/R cells.

Objective To evaluate the clinical value of acetic acid with narrow-band imaging ( NBI ) and magnifying endoscopy ( ME ) on diagnosis of small colorectal polyps. Methods In this prospective study, 261 small colorectal polyps from 122 patients were observed by ME, NBI-ME, and acetic acid with NBI-ME, and then received endoscopic treatment. Endoscopic images were stored electronically and randomly allocated to 3 experts and 3 non-experts for diagnosis using Kudo pit pattern. The postoperative pathologic results acted as gold standard to evaluate the diagnostic accuracy of different endoscopic modes for small colorectal polyps. The image definition and interobserver agreement were compared among different endoscopic modes. Results The diagnostic accuracy of ME, NBI-ME, and acetic acid with NBI-ME for small colorectal polyps was 65. 5％ ( 171/261) , 90. 0％ ( 235/261) , and 94. 6％ ( 247/261) , respectively, in the experts group, and 57. 1％ ( 149/261) , 83. 1％ ( 217/261) , and 89. 3％ ( 233/261) , respectively, in the non-experts group. All experts and non-experts diagnosed small colorectal polyps more accurately by acetic acid with NBI-ME than by NBI-ME ( all P<0. 05 ) and ME ( all P<0. 001 ) . The image definition scores of acetic acid with NBI-ME in the experts group and non-experts group were significantly higher than those of NBI-ME and ME ( all P<0. 001) . The results of interobserver agreement showed that Kappa values (95％CI) of ME, NBI-ME, and acetic acid with NBI-ME diagnosis were 0. 578 (0. 508-0. 648), 0. 669 (0. 599-0. 739), and 0. 940 (0. 870-1. 010), respectively, for experts and 0. 476 (0. 406-0. 546), 0. 534 ( 0. 464-0. 604) , and 0. 830 ( 0. 760-0. 900 ) , respectively, for non-experts. Acetic acid with NBI-ME showed good interobserver agreement. Conclusion Acetic acid with NBI-ME has a higher diagnostic accuracy and good reproducibility for colorectal small polyps compared with ME and NBI-ME.