Circ_0061140 Potentiates Clear Cell Renal Cell Carcinoma Progression Via the MicroRNA-126-5p/ADAM9 Axis.

Circular RNAs (circRNAs) function as new cancer biomarkers, but the role of circ_0061140 remains unknown in clear cell renal cell carcinoma (ccRCC). Therefore, we aimed to validate the functions of circ_0061140 in ccRCC and its potential as a prognostic biomarker. At first, circ_0061140 expression in ccRCC tissues and cells was detected, and circ_0061140 was upregulated in ccRCC tissues (p < 0.0001) and cells (p < 0.0001). Patients with high expression of circ_0061140 had a worse prognosis (p < 0.05). Then, siRNA against circ_0061140 was transfected into Caki-1 and UT14 cells to explore its roles in the biological functions of ccRCC cells, and suppressing roles of downregulated circ_0061140 were observed in the cell growth of Caki-1 and UT14 cells (p < 0.01). Next, circ_0061140 was found to be a sponge of miR-126-5p, and ADAM9 was determined to be a target of miR-126-5p. Finally, functional rescue experiments were conducted to observe their roles in ccRCC cell growth. It was suggested that suppressed miR-126-5p or overexpressed ADAM9 induced cell proliferation and restricted cell apoptosis in ccRCC cells based on si-circ_0061140 (p < 0.01). Altogether, this study highlights that circ_0061140 plays an oncogenic role in ccRCC through modulation of the miR-126-5p/ADAM9 axis.

Intravesical Mucoadhesive Hydrogel Induces Chemoresistant Bladder Cancer Ferroptosis through Delivering Iron Oxide Nanoparticles in a Three-Tier Strategy.

Bladder cancer (BCa) is the most costly solid tumor owing to its high recurrence. Relapsed cancer is known to acquire chemoresistant features after standard intravesical chemotherapy. This cancer state is vulnerable to ferroptosis, which occurs when lipid peroxides generated by iron metabolism accumulate to lethal levels. Increasing the labile iron pool (LIP) by iron oxide nanoparticles (IONPs) promises to inhibit chemoresistant BCa (CRBCa), but systemically administered IONPs do not sufficiently accumulate at the tumor site. Therefore, their efficacy is weakened. Here, we present a three-tier delivery strategy through a mucoadhesive hydrogel platform conveying hyaluronic acid-coated IONPs (IONP-HA). When instilled, the hydrogel platform first adhered to the interface of the tumor surface, sustainably releasing IONP-HA. Subsequently, the tumor stiffness and interstitial fluid pressure were reduced by photothermal therapy, promoting IONP-HA diffusion into the deep cancer tissue. As CRBCa expressed high levels of CD44, the last delivery tier was achieved through antibody-mediated endocytosis to increase the LIP, ultimately inducing ferroptosis. This three-tiered strategy delivered the IONPs stepwise from anatomical to cellular levels and increased the iron content by up to 50-fold from that of systematic administration, which presents a potential regimen for CRBCa.

Arsenic Trioxide Combining Leflunomide Activates Nrf2-ARE-HO-1 Signaling Pathway and Protects Heart Xenografts.

OBJECTIVE: To investigate the molecular mechanisms underlying the effects of arsenic trioxide (As2O3) in combination with leflunomide on the hamster-to-rat heart xenotransplant. METHODS: Transplantation of LVG hamster hearts to Lewis rats was performed by anastomosis of vessels in the neck using end-to-end anastomosis with a non-suture cuff technique. Four groups of recipient rats (n=6 in each) were treated with normal saline (control), As2O3 [5 mg/(kg·day) intraperitoneally], leflunomide [5 mg/(kg·d) orally], or leflunomide [5 mg/(kg·d)+As2O3 [5 mg/(kg·d)] in combination. Donor hearts and/or rat spleens were harvested and analyzed 4 days after transplantation. Quantitative reverse-transcription polymerase chain reaction and Western blot analysis were performed to detect the expression of the nuclear factor erythroid-derived factor 2-related factor (Nrf2) and its target gene heme oxygenase-1 (HO-1), Treg cell marker fork-head Box P3 (FOXP3), apoptosis-associated proteins Bcl-2, Bax, and cleaved caspase-3. Immunohistochemical staining was used to detect the levels of inflammatory natural killer cell and macrophage infiltration, intercellular cell adhesion molecule-1 (ICAM-1) and complement C3. RESULTS: Expression of Nrf2-ARE-HO-1 signaling pathway was upregulated in heart xenografts in rats treated with As2O3 plus leflunomide compared with control rats or rats treated with either drug alone (P<0.01), and this was accompanied by an increased Treg cells in the recipient rat spleen (P<0.01). In contrast, the expressions of Bax, cleaved caspase-3, ICAM-1, and complement C3, and infiltration of inflammatory cells in the xenografts were inhibited by As2O3 plus leflunomide treatment (P<0.01). CONCLUSION: Combination treatment with As2O3 and leflunomide protected hamster heart-xenografts in recipient rats.

Integrated Analysis of the Roles of RNA Binding Proteins and Their Prognostic Value in Clear Cell Renal Cell Carcinoma.

Methods: We downloaded the RNA sequencing data of ccRCC from the Cancer Genome Atlas (TCGA) database and identified differently expressed RBPs in different tissues. In this study, we used bioinformatics to analyze the expression and prognostic value of RBPs; then, we performed functional analysis and constructed a protein interaction network for them. We also screened out some RBPs related to the prognosis of ccRCC. Finally, based on the identified RBPs, we constructed a prognostic model that can predict patients' risk of illness and survival time. Also, the data in the HPA database were used for verification. Results: In our experiment, we obtained 539 ccRCC samples and 72 normal controls. In the subsequent analysis, 87 upregulated RBPs and 38 downregulated RBPs were obtained. In addition, 9 genes related to the prognosis of patients were selected, namely, RPL36A, THOC6, RNASE2, NOVA2, TLR3, PPARGC1A, DARS, LARS2, and U2AF1L4. We further constructed a prognostic model based on these genes and plotted the ROC curve. This ROC curve performed well in judgement and evaluation. A nomogram that can judge the patient's life span is also made. Conclusion: In conclusion, we have identified differentially expressed RBPs in ccRCC and carried out a series of in-depth research studies, the results of which may provide ideas for the diagnosis of ccRCC and the research of new targeted drugs.

Nucleobindin-2 enhances the epithelial-mesenchymal transition in renal cell carcinoma.

Nucleobindin 2 (NUCB-2) is a multifunctional protein that contains several functional domains and is associated with a wide variety of biological processes, such as food intake and energy homeostasis. NUCB-2 has been demonstrated to be associated with worse malignant outcomes and cell migration in breast and prostate cancer. However, to the best of our knowledge, its clinical and biological significance in renal cell carcinoma remains unknown. In the present study, tissue specimens from 68 patients with renal cell carcinoma and 10 normal controls were collected for NUCB-2 mRNA and protein assays. The NUCB-2 level in the patients with renal cell cancer was significantly increased compared with the normal control patients. NUCB-2-knockout in the renal cancer cell line SK-RC-52 inhibited migration and invasion. In addition, the expression levels of molecules associated with epithelial-mesenchymal transition (EMT), including E-cadherin, ß-catenin, Slug and Twist, were affected by NUCB-2 suppression and the zinc finger E-box binding to homeobox 1 (ZEB1)-dependent pathway. The AMP-dependent protein kinase (AMPK)/target of rapamycin complex (mTORC) 1 signaling pathway participates in the regulation of NUCB-2-mediated metastasis and EMT. Suppression of NUCB-2 also inhibited tumor nodule formation in a murine renal cell carcinoma tumor model. In summary, NUCB-2 increased migration, invasion and EMT in renal cell carcinoma cells through the AMPK/TORC1/ZEB1 pathway in vitro and in vivo.

The Harbin Medical University nephrectomy score: a quantitative system for evaluating the complexity of laparoscopic retroperitoneal simple nephrectomy.

BACKGROUND: Laparoscopic retroperitoneal simple nephrectomy (LRSN) has been widely accepted as a mainstay option for benign non-functioning kidney. The complexity of the procedure, however, differs and remains a subject of controversy. OBJECTIVE: To develop a standardised Harbin Medical University nephrectomy score (HMUNS) system for evaluating LRSN complexity. SUBJECTS AND METHODS: A total of 6 variables with different factors comprising primary diseases, history of upper urinary tract surgery, body mass index (BMI), surgeon's learning curve, kidney volume, and Mayo Adhesive Probability (MAP) scores were included in the HMUN score. 95 consecutive patients who underwent LRSN at our institution were divided into low (2 to 6 points) and high (7 to 17 points) complexity groups with HMUNS and investigated the differences of operative time (OT), estimated blood loss (EBL), postoperative hospitalisation time (PHT), rate of intraoperative conversion to open surgery, and the Clavien-Dindo classifi cation (CDC) between both groups. RESULTS: Longer mean operative times (193.2±69.3 min vs. 151.9±46.3 min, p <0.05), more median estimated blood loss (100.0mL vs. 50.0mL, p <0.05), and higher rates of conversion to open surgery (1.2% vs. 25%, p <0.05) were observed in the high-complexity group (n=12) than in the low-complexity group (n=83). However, there were no remarkable differences between the two groups related to the baseline characteristics, post-surgical hospitalisation times, and postoperative complications. CONCLUSIONS: The HMUNS can effectively reflect LRSN complexity, thus providing a quantitative system for risk estimation and treatment decisions. Because of some limitations, further well-designed studies are necessary to confirm our fi ndings. Patient summary: The HMUNS, including primary diseases, history of upper urinary tract surgery, BMI, surgeon's learning curve, kidney volume, and MAP score, can provide an effective quantitative tool to evaluate the complexity of LRSN.

Circular RNA circ-Foxo3 induced cell apoptosis in urothelial carcinoma via interaction with miR-191-5p.

BACKGROUND: Circular RNAs (circRNAs) play a critical role in cancer. Emerging evidence has shown circ-Foxo3, a circRNA, was dysregulated in a variety of tumor types. However, the exact role of circ-Foxo3 in bladder cancer has never been studied. METHODS: We measured the expression level of circ-Foxo3 in human and murine bladder cancer tissues and in various human bladder cancer cell lines. We induced bladder cancer in mice by a carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). circ-Foxo3 was overexpressed in mice by lentiviral gene transfer and in cultured cells via overexpression plasmid. The effect of circ-Foxo3 on apoptosis was examined via apoptotic marker staining, Western blot, and flow cytometry. We further characterized the interaction between circ-Foxo3 and miR-191 and its functional impact on bladder cancer cells. RESULTS: circ-Foxo3 was downregulated in bladder cancer in vivo and in vitro, and was upregulated in response to apoptotic stress. Overexpression of circ-Foxo3 promoted bladder cancer cell apoptosis in BBN mice and in human bladder cancer cell lines. miR-191-5p suppressed circ-Foxo3 expression and the pro-apoptotic effect of circ-Foxo3 in bladder cancer cells via directly targeting the 3'-untranslated region (3'-UTR) of circ-Foxo3. CONCLUSION: circ-Foxo3 was downregulated in bladder cancer in vivo and in vitro, and promoted bladder cancer apoptosis via direct interaction with miR-191. circ-Foxo3 could be a potential therapeutic target for bladder cancer.

The Harbin Medical University nephrectomy score: a quantitative system for evaluating the complexity of laparoscopic retroperitoneal simple nephrectomy

ABSTRACT Background: Laparoscopic retroperitoneal simple nephrectomy (LRSN) has been widely accepted as a mainstay option for benign non-functioning kidney. The complexity of the procedure, however, differs and remains a subject of controversy. Objective: To develop a standardised Harbin Medical University nephrectomy score (HMUNS) system for evaluating LRSN complexity. Subjects and methods: A total of 6 variables with different factors comprising primary diseases, history of upper urinary tract surgery, body mass index (BMI), surgeon's learning curve, kidney volume, and Mayo Adhesive Probability (MAP) scores were included in the HMUN score. 95 consecutive patients who underwent LRSN at our institution were divided into low (2 to 6 points) and high (7 to 17 points) complexity groups with HMUNS and investigated the differences of operative time (OT), estimated blood loss (EBL), postoperative hospitalisation time (PHT), rate of intraoperative conversion to open surgery, and the Clavien-Dindo classification (CDC) between both groups. Results: Longer mean operative times (193.2±69.3 min vs. 151.9±46.3 min, p <0.05), more median estimated blood loss (100.0mL vs. 50.0mL, p <0.05), and higher rates of conversion to open surgery (1.2% vs. 25%, p <0.05) were observed in the high-complexity group (n=12) than in the low-complexity group (n=83). However, there were no remarkable differences between the two groups related to the baseline characteristics, post-surgical hospitalisation times, and postoperative complications. Conclusions: The HMUNS can effectively reflect LRSN complexity, thus providing a quantitative system for risk estimation and treatment decisions. Because of some limitations, further well-designed studies are necessary to confirm our findings. Patient summary: The HMUNS, including primary diseases, history of upper urinary tract surgery, BMI, surgeon's learning curve, kidney volume, and MAP score, can provide an effective quantitative tool to evaluate the complexity of LRSN.

SENP1 Interacts with HIF1α to Regulate Glycolysis of Prostatic Carcinoma Cells.

Background: Hypoxic microenvironment inside the tumor forces tumor cells to up-regulate the glycolytic pathway to maintain a sufficient energy supply for tumor growth. Activation of HIF1α under hypoxia condition is able to regulate the expression of glycolysis-related genes, and results in the proliferation and metastasis of cancer cells. However, the mechanism underlying HIF1α activation and glycolysis induction by hypoxia remains unclear. The present study is aimed to test if SENP1 regulates the glycolysis of prostate cancer cells (CaP) by improving stability of HIF1α protein. Methods: We employed qPCR and western blotting assay to analyze expression of HIF1α and SENP1. Glucose uptake assay, lactate production assay, LDH release assay and ATP production assay were utilized to evaluate cell glycolysis. The interaction between SENP1 and HIF1α was verified by co-immunoprecipitation assay. Results: We found that hypoxia condition improves glucose uptake and lactate production to sustain sufficient ATP for cellular activity in prostatic carcinoma cells. The expression of SENP1 mRNA was significantly increased in human prostatic carcinoma cell lines after exposure to hypoxia, accompanied by the up-regulation of HIF1α. Furthermore, forced expression of SENP1 was shown to regulate the glycolysis in prostatic carcinoma cells by stabilizing HIF1α. The up-regulation of SENP1 promotes tumor cell proliferation and tumorgenesis by interacting with HIF1α which was deSUMOylated and sequentially leading to a "Warburg effect". Conclusion: SENP1 interacts with HIF1α to regulate glycolysis and proliferation of prostatic carcinoma cells under hypoxia condition, which provides new insights into prostatic carcinoma therapy.

Upregulation of lncRNA snoRNA host gene 6 regulates NUAK family SnF1-like kinase-1 expression by competitively binding microRNA-125b and interacting with Snail1/2 in bladder cancer.

BACKGROUNDS/AIMS: Numerous studies have reported that long noncoding RNAs (lncRNAs) play critical roles in the development and progression of bladder cancer (BC). LncRNA snoRNA host gene 6 (SNHG6) is ectopically expressed in tumor tissues of patients with BC and BC cell lines. However, little is known about the molecular mechanism of SNHG6-mediated bladder urothelial carcinoma cell migration and invasion. METHODS: We detected the SNHG6 levels in human BC specimens and cell lines by quantitative real-time polymerase chain reaction and Western blot, and investigated its role in BC using in vitro assays. RESULTS: We showed that overexpression of SNHG6 induced epithelial-mesenchymal transition (EMT) and promoted the migration and invasion capabilities of BC cells. Mechanistically, SNHG6 induced EMT of BC cells by upregulating the expression levels of Snail1/2 and regulated BC cell migration and invasion by tumor suppressive hsa-miR-125b and its target gene NUAK Family Kinase 1 (NUAK1). Furthermore, we found that SNHG6 was positively correlated with Snail1/2 expression, and negatively correlated with hsa-miR-125b expression in BC specimens. Further study showed that SNHG6 repressed hsa-miR-125b expression to upregulate Snail1/2. Conversely, hsa-miR-125b knockdown augmented SNHG6 expression in BC cells. CONCLUSION: Overall, our study demonstrated that SNHG6 promotes BC cell migration and invasion partly via the hsa-miR-125b/Snail1/2/NUAK1 pathway. Therefore, SNHG6 may be a potential prognostic biomarker in BC, and targeting hsa-miR-125b/Snail1/2/NUAK1 axis may be a promising therapeutic approach for BC patients.

Bladder cancer cells induce immunosuppression of T cells by supporting PD-L1 expression in tumour macrophages partially through interleukin 10.

Immunotherapy based on BCG vaccination is an effective treatment in bladder cancer, but a positive response is restricted to a subset of patients and for a limited period of time only. This suggests that T cells antitumour responses are effective but can become compromised in bladder cancer. To investigate the underlying mechanisms, we first identified peripheral blood monocytes and tumour macrophages using the pan-monocyte/macrophage marker CD14, and found that the PD-L1 expression on the monocytes/macrophages in bladder cancer patients was significantly higher than that in controls. The monocytes from bladder cancer patients were also more capable at inducing apoptosis and inhibiting proliferation in activated autologous T cells than monocytes from controls, which was directly associated with the level of PD-L1 expression. We next investigated the tumour cells' participation in upregulating PD-L1 in monocytes/macrophages. Significant elevation of PD-L1 was observed in monocytes after culturing with autologous tumour cells, which did not require direct contact but required soluble factors. The STAT phosphorylation pattern in monocytes after tumour cell co-culture was consistent with effects of the interleukin (IL)-10 signalling pathway. We then found that removal of IL-10 in monocyte-tumour cell co-culture reduced the PD-L1 upregulation in monocytes, but IL-10 by itself was unable to directly upregulate PD-L1. Primary bladder tumour cells secreted significant levels of IL-10, indicating that they could serve as the source of IL-10. Together, these results demonstrated a novel pathway that bladder cancer cells induced immunosuppression of T cells by supporting PD-L1 expression in tumour macrophages partially through IL-10.

As2 O3 combined with leflunomide prolongs heart xenograft survival via suppressing the response of Th1, Th2, and B cells in a rat model.

Xenotransplantation remits the severe shortage of human organs and tissues for transplantation, which is a problem that severely limits the application of transplantation to the treatment of human disease. However, severe immune rejection significantly limits the efficacy of xenotransplantation. In this study, we systematically investigated the immunosuppressive effect and mechanism of action of As2 O3 and leflunomide using a hamster-to-rat heart xenotransplantation model. We initially examined heart xenograft survival following As2 O3 and leflunomide treatment alone or combined treatment. We found that treatment with As2 O3 combined with leflunomide can significantly prolong the survival of heart xenograft by inhibiting Th1 and Th2 differentiation and reducing the production of IgG and IgM. Interestingly, As2 O3 and leflunomide showed low toxicity to the organs of the recipient. Taken together, these observations indicate that treatment with As2 O3 combined with leflunomide may be a promising immunosuppressive schedule for xenotransplantation.

Laparoscopic Nephrectomy versus Open Nephrectomy for Patients with Autosomal Dominant Polycystic Kidney Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare efficacy and safety of laparoscopicnephrectomy (LN) versus open nephrectomy (ON) in the management of autosomal dominant polycystic kidney disease (ADPKD), we conducted a systematic review and meta-analysis. METHODS: A systematic search of the electronic databases PubMed, Scopus, and the Cochrane Library was performed up to October 2014. This systematic review was performed based on observational comparative studies that assessed the two techniques. The weighted mean difference (WMD) and risk ratio (RR), with their corresponding 95% confidence interval (CI), were calculated to compare continuous and dichotomous variables, respectively. RESULTS: Seven studies were identified, including 195 cases (118 LN/77 ON). Although LN was associated with longer operative time (WMD 30.236, 95%CI 14.541 -45.932, P<0.001) and the specimen might not have been resected as heavy as the ON group (WMD -986.516, 95%CI -1883.24--89.795, P = 0.031), patients in this group might benefit from a shorter length of hospital stay (WMD -3.576, 95%CI 4.976--2.176, P <0.001), less estimated blood loss (WMD -180.245, 95%CI -317.939--42.556, P = 0.010), and lower need of transfusion (RR 0.345, 95%CI 0.183-0.650, P = 0.001). The LN group also had less overall complications (RR 0.545, 95%CI 0.329-0.903, P = 0.018). The need of narcotic analgesics between the two groups might have no significant difference (WMD -54.66, 95%CI -129.76-20.44, P = 0.154). CONCLUSION: LN for giant symptomatic ADPKD was feasible, safe and efficacious. Morbidity was significantly reduced compared with the open approach. For an experienced laparoscopist, LN might be a better alternative.

Tumor-suppressive microRNA-145 induces growth arrest by targeting SENP1 in human prostate cancer cells.

Prostate cancer (PCa) prevails as the most commonly diagnosed malignancy in men and the third leading cause of cancer-related deaths in developed countries. One of the distinct characteristics of prostate cancer is overexpression of the small ubiquitin-like modifier (SUMO)-specific protease 1 (SENP1), and the upregulation of SENP1 contributes to the malignant progression and cell proliferation of PCa. Previous studies have shown that the expression of microRNA-145 (miRNA-145) was extensively deregulated in PCa cell lines and primary clinical prostate cancer samples. Independent target prediction methods have indicated that the 3'-untranslated region of SENP1 mRNA is a potential target of miR-145. Here we found that low expression of miR-145 was correlated with high expression of SENP1 in PCa cell line PC-3. The transient introduction of miR-145 caused cell cycle arrest in PC-3 cells, and the opposite effect was observed when miR-145 inhibitor was transfected. Further studies revealed that the SENP1 3'-untranslated region was a regulative target of miR-145 in vitro. MicroRNA-145 also suppressed tumor formation in vivo in nude mice. Taken together, miR-145 plays an important role in tumorigenesis of PCa through interfering SENP1.

2-Methoxyestradiol synergizes with sorafenib to suppress hepatocellular carcinoma by simultaneously dysregulating hypoxia-inducible factor-1 and -2.

Sorafenib is the approved systemic drug of choice for advanced hepatocellular carcinoma (HCC), but has demonstrated limited benefits because of drug resistance. 2-Methoxyestradiol (2ME2) has been shown to be a promising anticancer drug against various types of cancers and acts by dysregulating hypoxia-inducible factor (HIF)-1. Hypoxic cancer cells are extremely resistant to therapies since they elicit strong survival ability due to the cellular adaptive response to hypoxia, which is controlled by HIF-1 and HIF-2. The present study has demonstrated that sorafenib downregulated the expression of HIF-1α, making the hypoxic response switch from HIF-1α- to HIF-2α-dependent pathways, resulting in upregulation of HIF-2α, which contributes to the insensitivity of hypoxic HCC cells to sorafenib. HIF-2α played a dominant role in regulating VEGF, thus sorafenib in turn increased the expression of VEGF (a downstream molecule of both HIF-1 and HIF-2) and cyclin D1 (a downstream molecule of HIF-2), but reduced the expression of LDHA (a downstream molecule of HIF-1), in hypoxic HCC cells. 2ME2 significantly reduced the expression of both HIF-1α and HIF-2α, and their downstream molecules, VEGF, LDHA and cyclin D1, rendering hypoxic HCC cells to increased sensitivity to 2ME2. 2ME2 also inhibited the nuclear translocation of HIF-1α and HIF-2α proteins, but had no effect on their mRNA expression. 2M2 synergized with sorafenib to suppress the proliferation and induction of apoptosis of HCC cells in vitro and in vivo, and inhibited tumoral angiogenesis. These results indicate that 2ME2 given in combination with sorafenib acts synergistically for treating HCC.

Balloon dilation versus Amplatz dilation during ultrasound-guided percutaneous nephrolithotomy for staghorn stones.

BACKGROUND: Amplatz dilation and balloon dilation are different methods in creating the accesses during percutaneous nephrolithotomy (PCNL). The aim of this study was to review the surgical experiences of managing staghorn calculi by Amplatz dilation and balloon dilation for 3 years. METHODS: We retrospectively analyzed clinical data from 125 patients (129 kidneys) with staghorn kidney stones who underwent PCNL from January 2010 to December 2012, of whom 60 patients underwent Amplatz dilation (AD group) and 65 underwent balloon dilation (BD group) during PCNL. RESULTS: The AD and BD groups were similar in age, male-female ratio, stone burden, stone type, hydronephrosis, and proportion of patients who had undergone extracorporeal lithotripsy. However, these two groups showed significant differences in terms of duration of percutaneous access (15.1 ± 3.6) minutes vs. (10.0 ± 3.3) minutes, one-attempt success rate of dilation via a single access 88.9% (72/81) vs. 97.8% (91/93), hemoglobin drop after surgery (3.5 ± 0.9) g/dl vs. (1.7 ± 0.9) g/dl, number of cases requiring intraoperative and postoperative blood transfusion 27.9% (n = 17) vs. 13.2% (n = 9), changes of central venous pressure before and after surgery (2.3 ± 1.2) cmH2O vs. (1.2 ± 0.7) cmH2O, number of patients who experienced postoperative fever >37.5°C 21 (34.4%) vs. 13 (19.1%) (all P < 0.05). No injury of adjacent organs, including pleura, liver, spleen, or bowel, was noted in patients. CONCLUSIONS: During ultrasound-guided PCNL for staghorn stones, balloon dilation and Amplatz dilation are all effective and safe. Compared with Amplatz dilation, balloon dilation is a better choice, as it has a higher access creation success rate, shorter access creation time less blood loss, and lower proportions of circulatory overload and postoperative fever.

Transperitoneal approach versus retroperitoneal approach: a meta-analysis of laparoscopic partial nephrectomy for renal cell carcinoma.

OBJECTIVE: To compare the efficiency and safety of the transperitoneal approaches with retroperitoneal approaches in laparoscopic partial nephrectomy for renal cell carcinoma and provide evidence-based medicine support for clinical treatment. METHODS: A systematic computer search of PUBMED, EMBASE, and the Cochrane Library was executed to identify retrospective observational and prospective randomized controlled trials studies that compared the outcomes of the two approaches in laparoscopic partial nephrectomy. Two reviewers independently screened, extracted, and evaluated the included studies and executed statistical analysis by using software STATA 12.0. Outcomes of interest included perioperative and postoperative variables, surgical complications and oncological variables. RESULTS: There were 8 studies assessed transperitoneal laparoscopic partial nephrectomy (TLPN) versus retroperitoneal laparoscopic partial nephrectomy (RLPN) were included. RLPN had a shorter operating time (SMD = 1.001,95%confidence interval[CI] 0.609-1.393,P<0.001), a lower estimated blood loss (SMD = 0.403,95%CI 0.015-0.791,P = 0.042) and a shorter length of hospital stay (WMD = 0.936 DAYS,95%CI 0.609-1.263,P<0.001) than TLPN. There were no significant differences between the transperitoneal and retroperitoneal approaches in other outcomes of interest. CONCLUSIONS: This meta-analysis indicates that, in appropriately selected patients, especially patients with intraperitoneal procedures history or posteriorly located renal tumors, the RLPN can shorten the operation time, reduce the estimated blood loss and shorten the length of hospital stay. RLPN may be equally safe and be faster compared with the TLPN.

Antitumor effects of mutant endostatin are enhanced by Bcl-2 antisense oligonucleotides in UM-UC-3 bladder cancer cell line.

BACKGROUND: Endostatin is a potent inhibitor of tumor angiogenesis. In the preliminary studies, we developed a mutant endostatin containing Arg-Gly-Asp-Arg-Gly-Asp (RGDRGD) sequences. In this study, we compared the antitumor effects of mutant endostatin and Bcl-2 antisense oligonucleotides both in combination and individually. METHODS: The artificially synthesized Bcl-2 ASODN (antisense oligonucleotides) included a translation-initiation site and was transfected into the bladder cancer cells by Lipofectamine. Cell growth was investigated by the tumor cell growth chart, MTT assay, caspase-3 activity detection assay, AO/EB fluorescein stain, and the annexin V-FITC apoptosis detection assay. In the in vivo study, UM-UC-3 bladder cancer cells were subcutaneously implanted into nude mice and the growth of tumor was examined. The ultrastructure of the tumor tissues in the treated and control groups were observed. RESULTS: The cell growth chart showed that the cell population of the treated combination group decreased by 52.04% compared to the control group. The inhibition rate of the treated combination group was (79.66 ± 6.79)%, whereas those of the individual ASODN and ES groups were (53.39 ± 3.22)% and (50.22 ± 5.46)% respectively. In the caspase-3 activity detection using AO/EB fluorescein stain and annexin V-FITC apoptosis detection assay, the co-inhibitory effect was higher than the individual inhibitory effects (P < 0.05). There were significant differences in the inhibition of the solid tumor growth in the in vivo study. CONCLUSIONS: Our findings indicated that Bcl-2 antisense oligonucleotides enhance the antitumor effects of mutant endostatin both in vitro and in vivo. We noted the synergistic effects of Bcl-2 antisense oligonucleotides combined with mutant endostatin.

Down expression of LRP1B promotes cell migration via RhoA/Cdc42 pathway and actin cytoskeleton remodeling in renal cell cancer.

The low-density lipoprotein receptor-related protein 1B (LRP1B) is known as a putative tumor suppressor. The decreased expression of LRP1B has been involved in multiple primary cancers in several studies. However, its expression and function in the carcinogenesis of renal cell cancer (RCC) remain unclear. In this study, we investigated the expression of LRP1B in RCC by in situ hybridization (ISH) and real-time polymerase chain reaction (qRT-PCR). Our results indicated that LRP1B was frequently downexpressed in human RCC tissue and cell lines, which involved both epigenetic events (DNA methylation and histone deacetylation) and N-terminal deletion of LRP1B. Moreover, we testified that knockdown of LRP1B by shRNA significantly promoted anchorage-independent growth, cell migration and invasion in HEK293 cells and renal cancer cells 127 in vitro. We further found that silencing of LRP1B altered the expression of focal adhesion complex-associated proteins, and Cdc42/RhoA activities, which regulate the cytoskeleton dynamics. Taken together, these results strongly support that LRP1B may function as a tumor suppressor against renal cell cancer, and may regulate cell motility via RhoA/Cdc42 pathway and actin cytoskeleton reorganization in RCC.

Laparoscopic versus open nephroureterectomy for the treatment of upper urinary tract urothelial carcinoma: a systematic review and cumulative analysis of comparative studies.

CONTEXT: Laparoscopic nephroureterectomy (LNU) has increasingly been used as a minimally invasive alternative to open nephroureterectomy (ONU), but studies comparing the efficacy and safety of the two surgical procedures are still limited. OBJECTIVE: Evaluate the oncologic and perioperative outcomes of LNU versus ONU in the treatment of upper urinary tract urothelial carcinoma. EVIDENCE ACQUISITION: A systematic review and cumulative analysis of comparative studies reporting both oncologic and perioperative outcomes of LNU and ONU was performed through a comprehensive search of the Medline, Embase, and the Cochrane Library electronic databases. All analyses were performed using the Review Manager (RevMan) v.5 (Nordic Cochrane Centre, Copenhagen, Denmark) and Meta-analysis In eXcel (MIX) 2.0 Pro (BiostatXL) software packages. EVIDENCE SYNTHESIS: Twenty-one eligible studies (1235 cases and 3093 controls) were identified. A significantly higher proportion of pTa/Tis was observed in LNU compared to ONU (27.52% vs 22.59%; p = 0.047), but there were no significant differences in other stages and pathologic grades (all p>0.05). For patients who underwent LNU, the 5-yr cancer-specific survival (CSS) rate was significantly higher, at 9% (p = 0.03), compared to those who underwent ONU, while the overall recurrence rate and bladder recurrence rate were notably lower, at 15% (p = 0.01) and 17% (p = 0.02), respectively. However, there were no statistically significant differences in 2-yr CSS, 5-yr recurrence-free survival (RFS), 5-yr overall survival (OS), 2-yr OS, and metastasis rates between LNU and ONU (all p>0.05). Moreover, there were no significant differences between LNU and ONU in terms of intraoperative complications, postoperative complications, and perioperative mortality (all p>0.05). The results of our study were mainly limited by the retrospective design of most of the individual studies included as well as selection biases based on different management of regional lymph nodes and pathologic characteristics. CONCLUSIONS: Our data suggest that LNU offers reliable perioperative safety and comparable oncologic efficacy when compared to ONU. Given that some limitations cannot be overcome, well-designed prospective trials are needed to confirm our findings.