Survivin (encoded by the gene BIRC5) plays an important role in the carcinogenesis of bladder cancer. Identifying miRNAs that target Survivin in the setting of bladder cancer will help to develop Survivin-based therapies for bladder cancer. The expression levels of miR-138-5p and Survivin protein were measured in 12 resected bladder cancer specimens. The correlation between miR-138-5p and Survivin was further examined by evaluating Survivin expression in human bladder cancer cell lines that either overexpressed or knocked down miR-138-5p. A luciferase reporter assay was performed to test the direct binding of miR-138-5p to the target gene BIRC5. We also investigated the biological role of miR-138-5p targeting to Survivin in bladder cancer cell lines both in vivo and in vitro. In this study, we found that the Survivin protein was either absent or weakly expressed in normal adjacent tissues and consistently up-regulated in bladder cancer tissues; however, the mRNA levels did not vary as much, suggesting that a post-transcriptional mechanism was involved. Because microRNAs are powerful post-transcriptional regulators of gene expression, we used bioinformatic analyses to search for microRNAs that could potentially target BIRC5 in the setting of bladder cancer. We identified 2 specific targeting sites for miR-138-5p in the 3′ untranslated region (3′-UTR) of BIRC5. We further identified an inverse correlation between miR-138-5p and Survivin protein levels in bladder cancer tissue samples. By overexpressing or knocking down miR-138-5p in bladder cancer cells, we experimentally confirmed that miR-138-5p directly recognizes the 3′-UTR of the BIRC5 transcript and regulates Survivin expression. Furthermore, the biological consequences of the targeting of BIRC5 by miR-138-5p were examined in vitro via cell proliferation and invasion assays and in vivo using a mouse xenograft tumor model. We demonstrated that BIRC5 repression by miR-138-5p suppressed the proliferative and invasive characteristics of bladder cancer cells and that miR-138-5p exerted an anti-tumor effect by negatively regulating BIRC5 in a xenograft mouse model. Taken together, our findings provide the first clues regarding the role of miR-138-5p as a tumor suppressor in bladder cancer by inhibiting BIRC5 translation.
27 January 2015 in Journal of Translational Medicine
Astaxanthin (ATX) is a powerful antioxidant that occurs naturally in a wide variety of living organisms. Previous studies have shown that ATX has effects of eliminating oxygen free radicals and can protect organs from ischemia/reperfusion (IR) induced injury. The present study was designed to further investigate the protective effects of ATX on oxidative stress induced toxicity in tubular epithelial cells and on IR induced renal injury in mice. ATX, at a concentration of 250 nM, attenuated 100 μM H2O2-inudced viability decrease of tubular epithelial cells. In vivo, ATX preserved renal function 12 h or 24 h post IR. Pretreatment of ATX via oral gavage for 14 consecutive days prior to IR dramatically prevented IR induced histological damage 24 h post IR. Histological results showed that the pathohistological score, number of apoptotic cells, and the expression of α-smooth muscle actin were significantly decreased by pretreatment of ATX. In addition, oxidative stress and inflammation in kidney samples were significantly reduced by ATX 24 h post IR. Taken together, the current study suggests that pretreatment of ATX is effective in preserving renal function and histology via antioxidant activity.
A positive surgical margin (PSM) is reported to have some connection to the occurrence of biochemical recurrence and tumor metastasis in prostate cancer after the operation. There are no clinically usable models and the study is to predict the probability of PSM after robot-assisted laparoscopic radical prostatectomy (RALP) based on preoperative examinations. It is a retrospective cohort from a single center. The Lasso method was applied for variable screening; logistic regression was employed to establish the final model; the strengthened bootstrap method was adopted for model internal verification; the nomogram and web calculator were used to visualize the model. All the statistical analyses were based on the R-4.1.2. The main outcome was a pathologically confirmed PSM. There were 151 PSMs in the 903 patients, for an overall positive rate of 151/903 = 16.7%; 0.727 was the adjusted C statistic, and the Brier value was 0.126. Hence, we have developed and validated a predictive model for PSM after RALP for prostate cancer that can be used in clinical practice. In the meantime, we observed that the International Society of Urological Pathology (ISUP) score, Prostate Imaging Reporting and Data System (PI-RADS) score, and Prostate-Specific Antigen (PSA) were the independent risk factors for PSM.
10 January 2020 in The International Journal of Medical Robotics and Computer Assisted Surgery
Radical cystectomy (RC) with pelvic lymph node dissection (PLND) and urinary diversion (UD) is considered the standard treatment for muscle invasive bladder cancer (MIBC). In a part of patients, RC procedure is aborted due to unresectable disease, other followed treatment like systemic chemotherapy, radiotherapy or cryotherapy may be a better option. The aim of present study was to report the preliminary results of transperineal cryotherapy for unresectable muscle invasive bladder cancer. From January 2011 to August 2013, 7 male patients with pT4b unresectable bladder cancer underwent bilateral ureterocutaneostomy. Two performed a pelvic lymph node dissection (PLND). Then primary transperineal cryosurgery for preserved bladder at the guidance of transrectal ultrasound (TRUS) was performed. All patients underwent a dual freeze-thaw cycle using third-generation cryotechnology with ultrathin 17-gauge cryoneedles. Computer tomography (CT) and/or magnetic resonance image (MRI)were performed at 3 month intervals after cryosurgery to determine whether progression or recurrence occurred. All cryosurgery was performed successfully, mean operation time was 76.43 ± 25.12 min (range 50-120 min), mean blood loss was 19.29 ± 15.92 ml (range 5-50 ml). Mean hospital stay was 3.86 ± 1.68 day (range 2-7 days). No operative related deaths occurred. Four patients dead due to the metastasis disease at the follow up time of 8, 15, 18 and 37 months, respectively. Six patients received postoperative therapy, of whom 5 patients were treated with combined chemoradiation, and the other one received chemotherapy alone. The progression free survival (PFS) of the 7 patients was 22.00 ± 14.61 months (range 3-40 months). The one, two and three year overall survival (OS) was 85.7%, 57.1% and 42.9%, respectively. Our results suggest that cryosurgery combination with chemoradiotherapy provide a safe and effective alternative method for unresectable pT4b bladder cancer. Longer follow-up is necessary to determine the sustained efficacy.