ABSTRACT
OBJECTIVE: Prostate cancer is the most commonly diagnosed cancer, and metastatic prostate cancer often leads to poor outcomes for patients. During the metastasis processes, cancer cells acquire a migratory and invasive phenotype. Epithelial to mesenchymal transition (EMT) has been implicated in multiple processes of prostate cancer development including migration, chemoresistance, and carcinogenesis. PATIENTS AND METHODS: Expressions of miR-181a in prostate tumor samples and cancer cells were measured by qRT-PCR. Epithelial or mesenchymal markers were detected by Western blot. Nuclear translocation of Smad 2/3 was measured by immunostaining of prostate cancer cells. RESULTS: In this study, we report an oncogenic role of microRNA-181a in prostate cancer cells and patients. MiR-181a is upregulated in metastatic prostate tumor samples compared with primary prostate tumors. Interestingly, we found that overexpression of miR-181a promotes prostate cancer cell migration and invasion. Moreover, we observed that overexpression of miR-181a contributes to an epithelial to mesenchymal transition phenotype in prostate cancer cells: the epithelial marker, E-cadherin was downregulated, and mesenchymal markers, N-cadherin, vimentin, and snail were upregulated. Consistently, the phosphorylation of Smad 2/3 and the nuclear localization of Smad 2/3 were increased by miR-181a expression. We identified that TGIF2 - a repressor of the Smad pathway - is a direct target of miR-181a in prostate cancer cells. Importantly, restoration of TGIF2 in miR-181a overexpressing prostate cancer cells inhibited the Smad pathway and EMT processes. CONCLUSIONS: This research identifies a molecular mechanism for microRNA-mediated cancer metastasis and improvement novel therapeutic avenue for metastatic prostate cancer patient treatments.
Subject(s)
Epithelial-Mesenchymal Transition/genetics , Homeodomain Proteins/genetics , MicroRNAs/genetics , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Repressor Proteins/genetics , Antigens, CD , Cadherins/metabolism , Cell Count , Cell Line, Tumor , Cell Movement , Down-Regulation , Homeodomain Proteins/biosynthesis , Homeodomain Proteins/metabolism , Humans , Male , MicroRNAs/metabolism , Neoplasm Metastasis , Prostatic Neoplasms/genetics , Repressor Proteins/biosynthesis , Repressor Proteins/metabolism , Smad Proteins/biosynthesis , Snail Family Transcription Factors/biosynthesis , Up-Regulation , Vimentin/biosynthesisSubject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Laparoscopy , Urologic Neoplasms/surgery , Urologic Surgical Procedures/methods , Urology/methods , Asia , Europe , Laparoscopy/adverse effects , Patient Selection , Postoperative Complications/etiology , Retrospective Studies , Risk Assessment , Risk Factors , South America , Time Factors , Treatment Outcome , United States , Urologic Surgical Procedures/adverse effectsABSTRACT
PURPOSE: To present our clinic experience with the Swiss Lithoclast pneumatic lithotripter in the endoscopic management of urinary calculi. PATIENTS AND METHODS: From August 1994 to December 1997, 145 patients with ureteral calculi and 5 patients with urethral calculi were treated with the Swiss Lithoclast. RESULTS: In the ureteral stone group, ureteroscopic addressing of the stones was successful in 133 patients. In 27 patients, the stones were partially fragmented and remained in situ or were pushed back to the calices. They were subsequently treated successfully with SWL. Stones were fragmented in a single session in 101 cases. Complications associated with the procedure included five perforations and four urinary tract infections. All of the five urethral stone patients were treated successfully with pneumatic lithotripsy. The overall successful fragmentation rate thus was 70.7% (106 of 150) and 88.7% (133 of 150) in combination with adjuvant SWL. CONCLUSIONS: We have found Swiss Lithoclast pneumatic lithotripsy to be a safe, effective, and economical treatment method for urinary calculi. If combined with other modalities such as SWL, this treatment will be even more effective.