Doxorubicin Promotes Migration and Invasion of Breast Cancer Cells through the Upregulation of the RhoA/MLC Pathway / 한국유방암학회지

PURPOSE: Cancer cells develop acquired resistance induced by chemotherapeutic drugs. In this study, we investigated the effects of brief treatment with cytotoxic drugs on the phenotype of breast cancer cells. METHODS: Breast cancer cells MCF7 and BT-474 were briefly treated with paclitaxel or doxorubicin. Clonogenic, migration, and invasion assays were performed on the treated cells. Western blot analysis and RhoA activity assay were also performed. RESULTS: Breast cancer cells when briefly treated with paclitaxel or doxorubicin showed reduced clonogenic ability. Doxorubicin, but not paclitaxel, augmented cell migration and invasion. The invasion-promoting effects of doxorubicin were lost when the two drugs were sequentially used in combination. Myosin light chain (MLC) 2 phosphorylation and RhoA activity were upregulated by doxorubicin and downregulated by paclitaxel. Pretreatment with RhoA inhibitors abolished the migration- and invasion-promoting effects of doxorubicin. CONCLUSION: Doxorubicin activates the RhoA/MLC pathway and enhances breast cancer cell migration and invasion. Therefore, this pathway might be explored as a therapeutic target to suppress anthracycline-enhanced tumor progression.

The Feasibility of Using Simulated Targets in the Stomachs of Live Pigs for Full Endoscopic Submucosal Dissection Training

BACKGROUND/AIMS: In endoscopic submucosal dissection (ESD) training, only a flat target lesion can usually be simulated in the normal mucosa. This study aimed to evaluate the feasibility of simulated targets in the stomachs of live pigs for complete training. METHODS: Six trained endoscopists with hands-on experience with ex vivo, isolated pig stomachs were enrolled in this pilot study. An endoscopic banding device was used to create a polyp that was snared, leaving an ulcerated lesion. This simulated target model was used to perform ESD in pigs. The en bloc resection rate, procedure time, complications, quality of resection, and participants' opinions on the simulated targets were compared with the conventional model. RESULTS: En bloc resections were achieved in all six simulated targets and six conventional models. The mean size of the resected specimens was 32.2 mm (range, 20 to 39 mm) in the simulated target group and 23.5 mm (range, 11 to 40 mm) in the conventional group. The target model had a high quality of resection and had a high satisfaction rate for margin identification and correct peripheral marking. CONCLUSIONS: Good identification of the lesion and ease of periphery marking in the target model may improve resection quality.