No abstract

Substantial evidence suggests that cancer stem cells (CSCs) are the main cause of the initiation, progression and recurrence of tumors. Benzidine has been identified as a risk factor for bladder cancer. The aim of the present study was to investigate the effects of benzidine on bladder CSCs (BCSCs) and the possible mechanism underlying its action. The bladder cancer cell lines UM-UC-3 and EJ were maintained in serum-free medium and cells forming three-dimensional spheres were characterized as BCSCs. The sphere-forming cells were exposed to different concentrations of benzidine and vismodegib, and western blotting was performed to evaluate the expression of markers associated with CSCs and the Sonic hedgehog (SHH) signaling pathway. Flow cytometry was used to detect the distribution of cells in different phases of the cell cycle, and immunofluorescence staining was used to detect the protein expression of CD44. The results revealed that the levels of BCSC markers, namely CD133, CD44, aldehyde dehydrogenase 1-A1, Nanog and octamer-binding transcription factor-4, in the cell spheres were markedly elevated compared with those in cells cultured in serum-supplemented medium. Furthermore, benzidine increased the expression of BCSC markers and promoted the sphere-forming ability of the cells. In addition, it was observed that benzidine activated the SHH pathway, while inhibition of the Shh pathway using vismodegib diminished the promoting effects of benzidine on BCSCs. The findings of the present study indicate that benzidine promoted the stemness of BCSCs via activation of the SHH pathway, which may support further exploration of the molecular basis of the association between benzidine exposure and bladder oncogenesis.

Renal cell carcinoma (RCC) is a lethal urologic tumor commonly seen in men that best responds to partial nephrectomy. An enhanced understanding of the molecular pathogenesis of RCC can broaden treatment options and tumor prevention strategies. Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase that regulates several bioactive substances, and the present study aimed to identify the role of SIRT1/AMP-activated protein kinase (AMPK) signaling in RCC progression. SIRT1 expression was detected in 100 patients with RCC using tissue microarray immunohistochemistry. SIRT1-knockdown and overexpression were performed via RNA interference and plasmid transfection. Inhibition of AMPK was used for the phenotypic rescue assays to verify whether AMPK was a downstream target of SIRT1. Reverse transcription-quantitative PCR was performed to verify transfection efficiency. Transwell, MTT and flow cytometry apoptosis assays were performed to evaluate the migration, invasion, proliferation and early apoptosis level of RCC cells. SIRT1 and AMPK protein expression in human RCC tissues and cell lines (786-O and ACHN) was detected using western blotting and immunofluorescence staining. The current results, combined with data from The Cancer Genome Atlas database, revealed that SIRT1 expression in RCC tissues was downregulated compared with in adjacent normal tissues. Additionally, high SIRT1 expression was associated with an improved prognosis in patients with RCC. Overexpression of SIRT1 inhibited the proliferation, migration and invasion of RCC cell lines and induced apoptosis, while inhibition of SIRT1 expression had the opposite effects. Further experiments indicated that SIRT1 may serve an anticancer role by upregulating the expression levels of downstream AMPK, thus revealing a potential therapeutic target for RCC.

Background This study aimed to evaluate the effect of the three-port approach and conventional five-port laparoscopic radical cystectomy (LRC) with an ileal conduit. Methods Eighty-four patients, who were diagnosed with high-risk non-muscle-invasive and muscle-invasive bladder carcinoma and underwent LRC with an ileal conduit between January 2018 and April 2020, were retrospectively evaluated. Thirty and fifty-four patients respectively underwent the three-port approach and five-port LRC. Clinical characteristics, pathological data, perioperative outcomes, and follow-up data were analysed. Results There were no differences in perioperatively surgical outcome, including pathology type, prostate adenocarcinoma incidence, tumour staging, and postoperative creatinine levels between the two groups. The operative time (271.3 ± 24.03 vs. 279.57 ± 48.47 min, P = 0.299), estimated blood loss (65 vs. 90 mL, P = 0.352), time to passage of flatus (8 vs. 10 days, P = 0.084), and duration of hospitalisation post-surgery (11 vs. 12 days, P = 0.922) were no clear difference between both groups. Compared with the five-port group, the three-port LRC group was related to lower inpatient costs (12 453 vs. 14 134 $, P = 0.021). Our follow-up results indicated that the rate of postoperative complications, 90-day mortality, and the oncological outcome did not show meaningful differences between these two groups. Conclusions Three-port LRC with an ileal conduit is technically safe and feasible for the treatment of bladder cancer. On comparing the three-port LRC with the five-port LRC, our technique does not increase the rate of short-term and long-term complications and tumour recurrence, but the treatment costs of the former were reduced.

There have been some conflicting claims whether larger prostate weight (PW) reduces the risk of positive surgical margins (PSMs). This study aims to examine the associations between PW and PSMs. PubMed, Web of Science and Cochrane library were systematically retrieved. Relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were synthesised utilising random‐effect models. Ultimately, 22 cohort studies met criteria were enrolled in this meta‐analysis, of which 18 studies reporting the RR of the highest VS lowest category of PW yielded the combined RR of PSMs of 0.61 (95% CI 0.50–0.74). Subgroup analysis showed that geographic region and surgical modalities were considered as potential confounders of influence of PW on PSMs. The nonlinear dose–response relationship demonstrated that PSM risk decreased by 1% (RR = 0.99, 95% CI, 0.98–0.99) for every one gram increment in PW. This study suggests PW has a negative association with risk of PSMs, and having a appropriate PW is very important.