Mingxi Xu

miR-203 inhibition of renal cancer cell proliferation, migration and invasion by targeting of FGF2.

BackgroundRenal cell carcinoma (RCC) is one of the leading causes of cancer related mortality worldwide. Increasing evidence has shown that microRNAs function as oncogenes or tumor suppressors in human malignancies, but the roles of miR-203 in human RCC is still unclear.MethodsFirst, quantitative real-time PCR (qRT-PCR) was performed to detect miR-203 expression in renal cancer cell lines and clear cell RCC (ccRCC) specimens. Then, the association of miR-203 expression with clinicopathological features and survival was later analyzed. Finally, the roles of miR-203 in regulation of tumor proliferation, migration, invasion, and target gene expression were further investigated.ResultsOur study showed miR-203 was down-regulated in renal cancer cell lines and ccRCC specimens (P < 0.05). Respectively, the low miR-203 expression in ccRCC specimens was associated with advanced clinical features and poorer prognosis (P < 0.05). miR-203 expression was an independent prognostic marker of overall ccRCC patient survival in a multivariate analysis (P < 0.05). Transient forced expression of miR-203 inhibited renal cancer cell growth and metastasis (P < 0.05). In contrast, down-regulation of miR-203 expression promoted renal cancer cell growth and metastasis (P < 0.05). Mechanistic investigations confirmed FGF2 as a direct target of miR-203, and up-regulation of miR-203 could decrease expression of FGF2. Further investigation showed that ectopic expression of FGF2 partially reversed the inhibition effect of enforced miR-203 expression on the malignant phenotypes of renal cancer cells.ConclusionsOur study suggested that miR-203 could be a potential prognostic marker and functions as a tumor suppressor in human renal cancer by post-transcriptionally targeting FGF2.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6828145701534108.

Metastatic tumors of the penis: a report of 8 cases and review of the literature

AbstractThe purpose of this study was to report the clinical characteristics, treatments, and outcomes of secondary penile cancers and review the literature of this rare condition.The records of 8 patients with metastatic penile cancer treated at our hospital from 2006 to 2013 were analyzed. A search of medical databases was conducted.Patient symptoms included penile mass (n = 7, 5 had concomitant pain) and acute urine retention (n = 1). The primary cancers included bladder, lung, gastric, liver, and prostate malignancies and 1 case of pulmonary epithelioid hemangioendothelioma. The longest time from diagnosis of the primary cancer to metastatic penile cancer was 16 years and the shortest was 7 months. Six patients were treated with phallectomy, 1 with resection of the mass, and 1 with only a biopsy because of advanced metastatic disease. Five patients are deceased at the time of this report, and the longest and shortest survival times (from the diagnosis of primary cancer to the death) were 16 years and 9 months, respectively. The literature review identified 17 cases reported since 2011, bringing the total number of reported cases to 480. Genitourinary cancer, primarily bladder and prostate, account for approximately 70 of the primary cancer sites and gastrointestinal cancers account for approximately 21%. Approximately half of the patients had died of their disease within 1 year of the diagnosis of penile metastasis.The prognosis of metastatic penile cancer is poor. Most primary cancers are in the urologic or gastrointestinal systems. Surgery and adjunctive therapy may improve symptoms, but fail to prolong survival.

The Differentiation of Human Adipose-Derived Stem Cells towards a Urothelium-Like Phenotype In Vitro and the Dynamic Temporal Changes of Related Cytokines by Both Paracrine and Autocrine Signal Regulation

Purpose To investigate the differentiation ability of human adipose-derived stem cells (ASCs) towards urothelium-like cells in vitro and the dynamic changes of related cytokines and cytokine receptors in the culture medium. Materials and Methods The ASCs were induced using both conditioned media (CM) and the transwell co-culture system with an immortalized urothelium cell line (SV-HUC-1,HUC) for 21 days. Protein and mRNA expression of the mature urothelium specific markers uroplakin-IA (UP-1A) and uroplakin-II (UP-II) were detected by immunofluorescence and quantitative real-time PCR, respectively. Array detection was used to screen 41 cytokines and receptors in the upper medium of urothelium, non-induced ASCs and urothelium-induced ASCs at three time points, early (12 hours), intermediate (7 days) and late (21 days). Results After induction for 7 days, the ASCs grown in both CM and transwell co-culture system expressed uroplakin-IA (13.54±2.00%; 17.28±1.84%) and uroplakin-II (19.49±1.73%; 13.98±1.47%). After induction for 21 days, ASCs grown in co-culture had significantly increased expression of uroplakin-IA (48.03±1.25%; 49.57±2.85%) and uroplakin-II (45.38±2.50%; 46.58±1.95%). In the upper medium of urothelium, 28 cytokines and 8 cytokine receptors had significantly higher expression than the counterpart of non-induced ASCs. After 7 days induction, the expression of 22 cytokines and 8 cytokine receptors was significantly elevated in the upper medium of induced ASCs compared to non-induced ASCs. At the early and intermediate time points, ASCs secreted high levels of relative cytokines and soluble receptors, but their expressions decreased significantly at the late time point. Conclusion The adipose-derived stem cells have the potential to be differentiated into urothelium-like cells in vitro by both CM and transwell co-culture system with mature urothelium. Numerous cytokines and receptors were involved in the differentiation process with dynamic temporal changes by both paracrine and autocrine signal regulation. Further studies should be carried out to determine the detailed mechanism of cytokines and receptors and to enhance the urothelium differentiation efficiency of ASCs.

Two-stage urethroplasty is a better choice for proximal hypospadias with severe chordee after urethral plate transection: a single-center experience

It is still debatable whether single- or two-stage urethroplasty is a more suitable technique for treating hypospadias with severe chordee after urethral plate transection. This retrospective study evaluated these two techniques. A total of 66 patients of proximal hypospadias with severe chordee were divided into two groups according to the techniques they underwent: 32 and 34 patients underwent single-stage (Duckett) or two-stage urethroplasty, respectively. Median ages at presentation were 7.5 years and 11.0 years in single-stage and two-stage repair groups, respectively. Median follow-ups were 28.5 months (20−60 months) and 35 months (18−60 months) in the single-stage and two-stage groups, respectively. The meatus of the neourethra was located at the top of the glans in all patients. No recurrence of chordee was found during follow-up, and all patients or parents were satisfied with the penile length and appearance. Complications were encountered in eight patients in both groups, with no statistically significant differences between the two techniques. The late complication rate of stricture was higher after the single-stage procedure (18.75% vs 0%). The complication rate after single-stage repairs was significantly lower in the prepubescent subgroup (10.52%) than in the postpubescent cohort (46.15%). These results indicate that the urethral plate transection effectively corrects severe chordee associated with proximal hypospadias during the intermediate follow-up period. Considering the higher rate of stricture after single-stage urethroplasty, two-stage urethroplasty is recommended for proximal hypospadias with severe chordee after urethral plate transection.

The effects of RNA interference mediated VEGF gene silencing on biological behavior of renal cell carcinoma and transplanted renal tumor in nude mice.

OBJECTIVE This study was to explore the effects of RNA interference mediated vascular endothelial growth factor (VEGF) gene silencing on biological behavior of renal cell carcinoma (RCC), transplanted renal tumor and angiogenesis in nude mice. METHODS The specific siRNA sequence targeting VEGF were designed and synthesized to construct hVEGF-siRNA plasmid which was transfected into RCC 786-O cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for the detection of VEGF gene expression and western blot was adopted for the examination of VEGF protein expression. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell growth as well as cell migration and invasion. The transplanted renal tumor models in nude mice were established, and the growth condition of nude mice, and VEGF protein expression in transplanted tumor slices and the microvessel density (MVD) were detected. RESULTS The expression level of VEGF mRNA in VEGF-siRNA group was significant lower than that in the control group and negative group, suggesting that establishment of plasmid specifically inhibited the expression of VEGF gene The expression level of VEGF protein in VEGF-siRNA group was significant lower than that in the control group and negative group. VEGF gene silencing has the significant inhibition effects on proliferation, migration and invasion of RCC 786-O cells. The tumor weight, VEGF protein positive rate and MVD in VEGF-siRNA group were significant lower than those in negative group and blank group. CONCLUSION The VEGF gene silencing could inhibit the cell proliferation, migration and invasion of RCC 786-O cells; inhibition of VEGF protein expression could prevent transplanted RCC growth and tumor angiogenesis.

Losartan Preserves Erectile Function by Suppression of Apoptosis and Fibrosis of Corpus Cavernosum and Corporal Veno-Occlusive Dysfunction in Diabetic Rats

Background/Aims: Transforming growth factor-β1 (TGF-β1) plays important roles in penile corporal fibrosis and veno-occlusive dysfunction (CVOD). Angiotensin II (Ang II) is critically involved in erectile dysfunction, and blocking of Ang II is more important than inhibition of TGF-β in non-penile tissue fibrosis. However, the role of Ang II in corporal fbrosis and CVOD in a diabetic condition has not been investigated. Methods: Diabetic rats were treated with sildenafil or losartan (an Ang II antagonist) alone or in combination. Intracavernosal pressure, dynamic infusion cavernosometry, and histological and molecular alterations of the corpus cavernosum were examined. Results: Diabetic rats exhibited decreases in erectile response, severe CVOD, apoptosis, fibrosis, and activation of the TGF-β1 pathway. Treatment with sildenafil had a modest effect on erectile response and an insignificant suppressive effect on CVOD, apoptosis, fibrosis, and the TGF-β1 pathway. Although losartan greatly improved the histological and molecular changes and CVOD as compared with sildenafil, its effect on erectile response was low. The combination of sildenafil and losartan had superior effects on these parameters than did either compound alone. Conclusion: Ang II activation may be involved in apoptosis and fibrosis of the corpus cavernosum through Smad and non-Smad pathways, resulting in CVOD and ED. The low efficacy of sildenafil in a diabetic ED rat model was at least partly due to its inadequate effects on apoptosis, fibrosis, and CVOD.

Intraperitoneal incubation of bladder acellular matrix grafts improves bladder smooth muscle regeneration via neovascularization

The objective of this study was to investigate whether intraperitoneal incubation improves the regenerative capacity of bladder acellular matrix grafts (BAMGs) in a rat model of bladder augmentation. After 2 weeks of incubation in the peritoneum of male rats, BAMG flaps with vascular pedicles were harvested for autologous bladder augmentation. As the control, BAMGs were directly used for bladder augmentation without intraperitoneal incubation. Histological analyses of the incubated BAMGs demonstrated extensive cell growth and vasculature in homogeneous collagen bundles. The cells were positive for vimentin and negative for α-smooth muscle actin and pan-cytokeratin AE1/AE3. Cystography revealed smoother contours of the augmented bladders in the incubated group at 4 and 12 weeks postoperatively. However, the bladder capacity was not significantly different between the two groups. In both groups, the entire urothelium regenerated well without obvious differences. At both time points, compared with the control group, increased numbers of smooth muscle cells (SMCs) and blood vessels were found in the incubated group. At 12 weeks, the SMCs in the incubated group were more similar to those in the native smooth muscle fiber bundles of the bladder. Taken together, our results demonstrated that BAMGs preincubated in the peritoneum promote the regeneration of bladder smooth muscle via neovascularization in a rat bladder augmentation model.

Bisdemethoxycurcumin in combination with α-PD-L1 antibody boosts immune response against bladder cancer

Curcumin was recently discovered to strengthen immune response through multiple mechanisms. Cytotoxic CD8+ T-cells play a critical role in modulating anticancer immune response, but is severely restricted by T-cell exhaustion. Bladder carcinomas express PD-L1 and can abrogate CD8+ T-cell response. Thus, we hypothesized that bisdemethoxycurcumin, a natural dimethoxy derivative of curcumin, may provide a favorable environment for T-cell response against bladder cancer when used in combination with α-PD-L1 antibody. Immunocompetent C56BL/6 mouse models bearing subcutaneous or lung metastasized MB79 bladder cancer were established to validate this conjecture. We found that bisdemethoxycurcumin significantly increased intratumoral CD8+ T-cell infiltration, elevated the level of IFN-γ in the blood, and decreased the number of intratumoral myeloid-derived suppressor cells. Furthermore, α-PD-L1 antibody protected these amplified CD8+ T-cells from exhaustion, and therefore facilitated the secretion of IFN-γ, granzyme B, and perforin through these CD8+ T-cells. As a result, this combination treatment strategy significantly prolonged survival of intraperitoneal metastasized bladder cancer bearing mice, suggesting that bisdemethoxycurcumin in combination with α-PD-L1 antibody may be promising for bladder cancer patients.

Prevalence of Benign Prostatic Hyperplasia in Shanghai, China: A Community-based Study

Background and Objective: The prevalence of benign prostatic hyperplasia (BPH) in Shanghai, China, has not been updated in over 20 years. Here, we conducted a study in the community health system to get current BPH prevalence. Materials and Methods: All males older than 50 years old with lower urinary tract symptoms (LUTS) in five randomly selected communities in Shanghai were included in this study and were grouped according to their age. Group A was men with ages between 50 and 59, Group B 60-69, Group C 70-79, and Group D over 80. Results of international prostate symptom scores (IPSS), urinalysis, digital rectal examination, ultrasound scan, uroflowmetry, prostate specific antigen level, and any complications related to BPH were collected and analyzed. Results: The ages ranged from 50 to 92 (68.7 ± 9.6, mean ± standard deviation). The average IPSS in each group increased with aging, from 15.13 ± 2.87 in Group A to 19.95 ± 7.43 in Group D. However the quality of life scores (QoL) did not correlate with IPSS in Group A (r = 0.263, P < 0.001). The prevalence rate of BPH increased with aging. The growth rate of the prostate slowed from 27.86% to 8.84% from Group A to Group D. Conclusions: The overall prevalence rate of BPH in our study is 11.99%, LUTS symptoms develop with aging, and the result of the single-question QoL questionnaire should be carefully considered while dealing with patients in Shanghai older than 60.

Reconstruction of Major Scrotal Defects by Anterolateral Thigh Flap

To summarize the indications and applications of anterolateral thigh flaps (ALTP) in reparation and reconstruction of acute scrotum skin deficiency. We report our experience of treating three patients for scrotal reconstruction using the ALTP method from May of 2007 to December of 2010. The flap was completely islanded, tunneled beneath the fascial septa below the rectus femoris, and placed into the defect. The resulting reconstruction provided a tension-free, cosmetically appealing scrotum with complete testicular coverage. There were no perioperative or postoperative complications. Spermatogenesis (sperm count levels), and sexual function (IIEF) were not changed significantly. ALTP represent an excellent reconstruction option for patients with contaminated perineum. ALTP is available for replacement of the avulsed portion of the scrotal skin resulting in satisfactory shape and color of the penis and scrotum.