MicroRNAs are endogenous small noncoding RNAs that are functionally involved in numerous critical cellular processes including tumorigenesis. Data mining using a microRNA array database suggested that let-7d microRNA may be associated with renal cell carcinoma (RCC) malignant progression. Here, we performed further analyses to determine whether let-7d is functionally linked to RCC malignancy. Quantitative real-time PCR was used to determine the level of mature let-7d in RCC clinical specimens and its correlation with clinicopathological data. Immunohistochemical staining was conducted to characterize the stroma of RCC. Let-7d overexpressing RCC cell lines combined with mouse models bearing cell-derived xenografts and patient-derived xenografts were used to assess the functional role of let-7d in vitro and in vivo. Downregulation of let-7d in clinical RCC samples was associated with advanced tumor grade and T stage and increased vascular invasion. An inverse relationship between let-7d expression and macrophage infiltration was found in clinical RCC samples. Functional studies indicated that ectopic expression of let-7d significantly inhibited RCC cell proliferation, migration, and peripheral blood monocyte (PBMC) recruitment in vitro, as well as tumor growth, metastasis, and tumor macrophage infiltration in vivo. In silico analysis and subsequent experimental validation confirmed collagen, type III, alpha 1 (COL3A1) and C-C subfamily chemokine member CCL7 as direct let-7d target genes. The addition of COL3A1 and CCL7 counteracted the inhibitory effects of let-7d on RCC cell proliferation, migration, and PBMC recruitment. The inhibition of let-7d increased cell proliferation, migration, and PBMC recruitment by the enhanced expression of COL3A1 and CCL7 genes in vitro. The mRNA levels of COL3A1 and CCL7 were inversely correlated with let-7d level in RCC clinical specimens. These results suggest that let-7d may suppress RCC growth, metastasis, and tumor macrophage infiltration at least partially through targeting COL3A1 and CCL7.

Kaempferol (Kae), a natural flavonoid, is widely distributed in fruits and vegetables. Previous studies have identified Kae as a possible cancer preventive and therapeutic agent. We found Kae to exhibit potent antiproliferation and anti-migration effects in human bladder cancer EJ cells. Kaempferol robustly induced apoptosis in EJ cells in a dose-dependent manner, as evidenced by increased cleavage of caspase-3. Furthermore, we found Kae-induced apoptosis in EJ cells to be associated with phosphatase and the tensin homolog deleted on the chromosome 10 (PTEN)/PI3K/Akt pathway. Kae significantly increased PTEN and decreased Akt phosphorylation. Kae-induced apoptosis was partially attenuated in PTEN-knockdown cells. Our findings indicate that Kae could be an alternative medicine for bladder cancer, based on a PTEN activation mechanism.

The ureterointestinal anastomosis stricture (UAS) is a common complication of urinary diversion after radical cystectomy. For decades, open anastomotic revision remained the gold standard for the treatment of UAS. However, with the advancement in endoscopic technology, mini-invasive therapeutic approaches have been used in its management. Here, we report our experience with and long-term results of combined simultaneous antegrade and retrograde endoscopy (SARE) in the treatment of non-malignant UASs after urinary diversion in a consecutive series of patients. From March 2012 to January 2015, there were 32 consecutive patients with 32 non-malignant UASs following radical cystectomy and urinary diversion. Twenty-nine patients were treated with SARE technique and comprised the study group. Using simultaneous antegrade flexible ureteroscope combined with retrograde semi-rigid ureteroscope or nephroscope, partial or complete strictures were managed with laser incision and balloon dilation under direct visualization. A 7/12 Fr graded endopyelotomy stent was left for 3–6 months after the procedure. Success was defined as symptomatic improvement and radiographic resolution of obstruction. With a median followup of 22 months (6–36), the overall success rate for SARE was 69.0%. Twenty patients with partial stricture had a success rate of 85%, and 9 patients with complete stricture had a success rate of 33.3%. Renal function, hydronephrosis grade, stricture type, and stricture length were significant influences on the outcome (P < 0.05). No complication was observed. The SARE is a safe and effective treatment for UAS, and may be the only endoscopic treatment approach for complete UAS. While success rate for complete strictures is low compared to open revision, it should be considered as an initial approach given its low overall morbidity. For partial strictures, prudent patient selection results in higher success rates that are nearly comparable to open revision.