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2.
J Cell Mol Med ; 27(23): 3897-3910, 2023 12.
Article En | MEDLINE | ID: mdl-37859585

Renal cell carcinoma (RCC) is the most aggressive subtype of kidney tumour with a poor prognosis and an increasing incidence rate worldwide. Brusatol, an essential active ingredient derived from Brucea javanica, exhibits potent antitumour properties. Our study aims to explore a novel treatment strategy for RCC patients. We predicted 37 molecular targets of brusatol based on the structure of brusatol, and MEF2A (Myocyte Enhancer Factor 2A) was selected as our object through bioinformatic analyses. We employed various experimental techniques, including RT-PCR, western blot, CCK8, colony formation, immunofluorescence, wound healing, flow cytometry, Transwell assays and xenograft mouse models, to investigate the impact of MEF2A on RCC. MEF2A expression was found to be reduced in patients with RCC, indicating a close correlation with MEF2A deubiquitylation. Additionally, the protective effects of brusatol on MEF2A were observed. The overexpression of MEF2A inhibits RCC cell proliferation, invasion and migration. In xenograft mice, MEF2A overexpression in RCC cells led to reduced tumour size compared to the control group. The underlying mechanism involves the inhibition of RCC cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) through the modulation of Wnt/ß-catenin signalling. Altogether, we found that MEF2A overexpression inhibits RCC progression by Wnt/ß-catenin signalling, providing novel insight into diagnosis, treatment and prognosis for RCC patients.


Carcinoma, Renal Cell , Kidney Neoplasms , Animals , Humans , Mice , beta Catenin/genetics , beta Catenin/metabolism , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , MEF2 Transcription Factors/drug effects , MEF2 Transcription Factors/genetics , MEF2 Transcription Factors/metabolism , Wnt Signaling Pathway/drug effects
3.
Sci Adv ; 9(31): eadf3566, 2023 08 02.
Article En | MEDLINE | ID: mdl-37531433

For clear cell renal cell carcinoma (ccRCC), lipid deposition plays important roles in the development, metastasis, and drug resistance. However, the molecular mechanisms underlying lipid deposition in ccRCC remain largely unknown. By conducting an unbiased CRISPR-Cas9 screening, we identified the epigenetic regulator plant homeodomain finger protein 8 (PHF8) as an important regulator in ccRCC lipid deposition. Moreover, PHF8 is regulated by von Hippel-Lindau (VHL)/hypoxia-inducible factor (HIF) axis and essential for VHL deficiency-induced lipid deposition. PHF8 transcriptionally up-regulates glutamate-ammonia ligase (GLUL), which promotes the lipid deposition and ccRCC progression. Mechanistically, by forming a complex with c-MYC, PHF8 up-regulates TEA domain transcription factor 1 (TEAD1) in a histone demethylation-dependent manner. Subsequently, TEAD1 up-regulates GLUL transcriptionally. Pharmacological inhibition of GLUL by l-methionine sulfoximine not only repressed ccRCC lipid deposition and tumor growth but also enhanced the anticancer effects of everolimus. Thus, the PHF8-GLUL axis represents a potential therapeutic target for ccRCC treatment.


Carcinoma, Renal Cell , Glutamate-Ammonia Ligase , Histone Demethylases , Kidney Neoplasms , Transcription Factors , Humans , Carcinoma, Renal Cell/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Histone Demethylases/metabolism , Kidney Neoplasms/metabolism , Lipids , Protein Processing, Post-Translational , Transcription Factors/genetics , Transcription Factors/metabolism , Glutamate-Ammonia Ligase/metabolism
4.
Front Cell Infect Microbiol ; 13: 1145196, 2023.
Article En | MEDLINE | ID: mdl-37313343

Background: The incidence of nephrolithiasis is increasing rapidly worldwide. Calcium oxalate is the most common constituent, contributing to approximately 80% of all kidney stones. The gut microbiome, through its oxalate-degrading ability, may play a role in decreasing morbidity due to urinary calculus. Fecal microbiome transplantation (FMT) has been reported to be effective in restoring the gastrointestinal microbial community in different conditions. The transplantation of whole communities that have oxalate-degrading function may be a more effective strategy than the transplantation of isolated strains. Methods: FMT was carried out in male guinea pigs and male Sprague-Dawley laboratory rats (SDRs). Fresh feces were collected from guinea pigs housed in metabolic cages. SDRs were divided into four groups: two groups received standard rat chow (SC) (groups SC and SC + FMT), and two groups were fed a 5% potassium oxalate diet (OD) (groups OD + phosphate-buffered saline (PBS) and OD + FMT). On day 14, groups OD + PBS, OD + FMT, and SC + FMT received either PBS or guinea pig feces by esophageal gavage. The composition of the microbiota of guinea pigs and SDRs was analyzed using a 16S rRNA gene sequencing approach. Biochemical analysis of urine samples from SDRs revealed the presence of calcium oxalate (CaOx) crystals, which were presumed to originate from kidney stones. Renal function was examined using real-time PCR analysis and immunohistochemical staining for renin, angiotensin-converting enzyme, and osteopontin (OPN) expression. Results: FMT resulted in a gut microbiota that was a mixture of guinea pig and SDR bacteria. A microbial network involving Muribaculaceae, Lactobacillus, and Bifidobacterium was activated by FMT in group OD + FMT. As a result, urinary oxalate, calcium, uric acid, creatinine and urea in urine samples were reduced significantly. Similarly, significant reduction of uric acid and blood urea nitrogen to creatinine ratio in serum samples was observed (p < 0.05). Microscopic observations revealed a high CaOx crystal score (4+) in the kidneys of rats in group OD + PBS, whereas a lower score (2+) was observed in the rats in group OD + FMT. Up-regulation of OPN and down-regulation of renin were also associated with FMT. Conclusion: A microbial network involving Muribaculaceae and other oxalate-degrading bacteria achieved by FMT was capable of reducing urinary oxalate excretion and CaOx crystal deposition in the kidney through increasing intestinal oxalate degradation. FMT may exert a renoprotective function in oxalate-related kidney stones.


Calcium Oxalate , Kidney Calculi , Male , Rats , Animals , Guinea Pigs , Fecal Microbiota Transplantation , Renin , Creatinine , RNA, Ribosomal, 16S/genetics , Uric Acid , Rats, Sprague-Dawley , Kidney/physiology , Bacteria/genetics , Bacteroidetes , Kidney Calculi/therapy , Oxalic Acid
5.
Contrast Media Mol Imaging ; 2022: 4107491, 2022.
Article En | MEDLINE | ID: mdl-35517991

Objective: To demonstrate the advantage of our newly designed magnetic ureteric stenting retrieval device over traditional nonmagnetic ureteric stents and other retrieval devices without cystoscopy intervention on clinical application and cost-related outcomes. Patients and Methods. A total of 333 patients were recruited into two study groups: magnetic-end ureteral stent (Group A) and conventional ureteral stent (Group B). The effects were evaluated by Ureteral Stent Symptom Questionnaire (USSQ) scores, complications of the indwelling stent, visual analog scale (VAS) pain scores at stent removal, and cost-analysis outcomes between the magnetic ureteric stenting retrieval device and traditional double-J ureteral stent (DJUS) removed by cystoscopy. Results: The VAS of the pain score of patients undergoing magnetic stent removal with the retrieval device was 2 ± 0.97, whereas that of patients undergoing conventional ureteral stent removal with cystoscopy was 5.76 ± 1.53 (p < 0.001). The removal of magnetic stents by a retrieval device proved to be less painful than cystoscopy-mediated stent removal (p < 0.001). Obviously, the total cost for the magnetic stent removal was much lower than the conventional ureteral stent removal, although the magnetic stent costs more than the conventional ureteral stent. The improved magnetic stent used in our study showed a remarkable cost saving of 705/111 USD Chinese Yuan (CNY) per patient when compared with the conventional ureteral stent. Conclusion: We reported the integrated design features of the improved magnetic stent in the world, which was granted a patent in China. USSQ scores and rate of complications in the magnetic stent were as equally acceptable as a conventional stent. Furthermore, successful stent insertion rate reached 100% by both the antegrade and retrograde approaches, and no failure case of magnetic stent removal was reported in our study.


Ureter , Humans , Magnetic Phenomena , Pain/etiology , Prospective Studies , Stents/adverse effects , Ureter/surgery
6.
Transl Androl Urol ; 10(8): 3386-3394, 2021 Aug.
Article En | MEDLINE | ID: mdl-34532263

BACKGROUND: To explore the efficacy and advantages of real-time navigation using holographic reconstruction (HR) technology combined with da VinciTM robotic system for partial nephrectomy (PN) in patients with renal tumor. METHODS: The clinical data of 41 patients with totally intrarenal tumors receiving robot-assisted partial nephrectomy (RAPN) from April 2018 to October 2020 in our department were collected and retrospectively analyzed. All operations were performed by the same surgeon. HR technology and three-dimensional (3D) reconstruction techniques were applied for real-time navigation to resect tumors using the da VinciTM robotic system. The relevant clinical parameters and surgical outcomes of the patients were recorded and analyzed. RESULTS: HR technology allowed accurate evaluation of tumors, renal hilus vessels, and surrounding organs during the operation. With real-time navigation HR, all cases were performed by RAPN. The mean operative time was 115.3±20.3 (range, 70-153) minutes, and the warm ischemia time (WIT) was 18.7±3.9 (range, 13-28) minutes. The estimated blood loss (EBL) was 98.8±18.7 (range, 60-141) mL. Negative surgical margins were reported in all cases. Patients with absence of grade ≤1 Clavien-Dindo complications. Compared with the clinical outcomes of standard RAPN, as reported in the literature, HR-assisted technology reduced the mean operative time, the WIT, and the EBL in patients undergoing RAPN. Therefore, combining HR with robotic abdominal surgery can enhance the efficiency of locating blood vessels and allow for more accurate resection of tumors. CONCLUSIONS: As a novel and promising computer digital technology, HR can significantly improve the success of RAPN operations. This retrospective study demonstrated that HR-assisted operations resulted in shorter operation times and less perioperative complications and were thus safer and more effective in patients with renal tumors compared with RAPN not used HR.

7.
Asian J Urol ; 7(3): 291-300, 2020 Jul.
Article En | MEDLINE | ID: mdl-32742929

OBJECTIVE: To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy (MIRC) or open radical cystectomy (ORC). METHODS: We identified patients with bladder cancer who underwent radical cystectomy (RC) in 13 centers of the Chinese Bladder Cancer Consortium (CBCC). Perioperative outcomes were compared between MIRC and ORC. The influence of surgical approaches on overall survival (OS) and cancer-specific survival (CSS) in the entire study group and subgroups classified according to pathologic stage or lymph node (LN) status was assessed with the log-rank test. Multivariable Cox proportional hazard models were used to evaluate the association among OS, CSS and risk factors of interest. RESULTS: Of 2 098 patients who underwent RC, 1 243 patients underwent MIRC (1 087 laparoscopic RC and 156 robotic-assisted RC, respectively), while 855 patients underwent ORC. No significant differences were noted in positive surgical margin rate and 90-day postoperative mortality rate. MIRC was associated with less estimated blood loss, more LN yield, higher rate of neobladder diversion, longer operative time, and longer length of hospital stay. There was no significant difference in OS and CSS according to surgical approaches (p=0.653, and 0.816, respectively). Subgroup analysis revealed that OS and CSS were not significantly different regardless of the status of extravesical involvement or LN involvement. Multivariable Cox regression analyses showed that the surgical approach was not a significant predictor of OS and CSS. CONCLUSIONS: Our study showed that MIRC was comparable to conventional ORC in terms of OS and CSS.

8.
Cell Biol Int ; 44(10): 2094-2106, 2020 Oct.
Article En | MEDLINE | ID: mdl-32639616

Prostate cancer (PCa) is one of the most common malignant tumors in the world. Thioredoxin interacting protein (TXNIP) is downregulated in a variety of human tumors and plays an important role in tumor suppression. However, the expression level and biological functions of TXNIP in PCa have not been identified yet. Therefore, this study aims to investigate the expression and biological functions of TXNIP in PCa. We reported that the expression of TXNIP was significantly decreased in PCa and associated with clinicopathological features. Overexpression of TXNIP could significantly inhibited PC-3 cells proliferation, migration, invasion, and glucose uptake. Additionally, overexpression of TXNIP could remarkably block cell cycle in the G0/G1 phase and promoted cell apoptosis. Furthermore, TXNIP expression correlated inversely with GLUT1 expression in PCa. Taken together, our results for the first time revealed that TXNIP was decreased in PCa. Moreover, TXNIP might act as a tumor suppressor of PCa and correlated with tumor occurrence and development. Our findings cast a new light on better understanding the occurrence and development of PCa and indicated that TXNIP might be favorable for PCa molecular target therapy.


Carrier Proteins/physiology , Gene Expression Regulation, Neoplastic , Genes, Tumor Suppressor , Prostatic Neoplasms , Aged , Apoptosis , Cell Cycle , Humans , Male , Middle Aged , PC-3 Cells , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology
9.
BJU Int ; 125(6): 801-809, 2020 06.
Article En | MEDLINE | ID: mdl-30958622

OBJECTIVES: To explore characteristics of urinary stone composition in China, and determine the effects of gender, age, body mass index (BMI), stone location, and geographical region on stone composition. PATIENTS AND METHODS: We prospectively used Fourier-transform infrared spectroscopy to analyse stones from consecutive patients presenting with new-onset urolithiasis at 46 hospitals in seven geographical areas of China, between 1 June 2010 and 31 May 2015. Chi-squared tests and logistic regression analyses were used to determine associations between stone composition and gender, age, BMI, stone location, and geographical region. RESULTS: The most common stone constituents were: calcium oxalate (CaOx; 65.9%), carbapatite (15.6%), urate (12.4%), struvite (2.7%), and brushite (1.7%). CaOx and urate stones occurred more frequently in males, whereas carbapatite and struvite were more common in females (P < 0.01). CaOx and carbapatite were more common in those aged 30-50 and 20-40 years than in other groups. Brushite and struvite were most common amongst those aged <20 and >70 years. The detection rate of urate increased with age, whilst cystine decreased with age. Obese patients were more likely to have urate stones than carbapatite or brushite stones (P < 0.01). CaOx, carbapatite, brushite, and cystine stones were more frequently found in the kidney than other types, whereas urate and struvite were more frequent in the bladder (P < 0.01). Stone composition varied by geographical region. CONCLUSIONS: The most common stone composition was CaOx, followed by carbapatite, urate, struvite, and brushite. Stone composition differed significantly in patients grouped by gender, age, BMI, stone location, and geographical region.


Urinary Calculi/chemistry , Urinary Calculi/epidemiology , Adolescent , Adult , Aged , Apatites , Body Mass Index , Calcium Oxalate , Child , Child, Preschool , China/epidemiology , Female , Humans , Infant , Male , Middle Aged , Prospective Studies , Spectroscopy, Fourier Transform Infrared , Young Adult
10.
Urol Int ; 101(2): 143-149, 2018.
Article En | MEDLINE | ID: mdl-29649833

OBJECTIVES: To investigate the safety, efficacy, and practicability of minimally invasive percutaneous nephrolithotomy (MPCNL) with the aid of a patented irrigation clearance system in treating renal staghorn calculi. METHODS: From August 2009 to July 2014, 4 hospitals had executed a prospective multicenter study with a total of 912 cases. The patients were randomly divided into 3 groups: suctioning MPCNL, standard percutaneous nephrolithotomy (PCNL), and traditional MPCNL groups. Multiple operative and perioperative parameters were compared. RESULTS: Blood loss and intrapelvic pressure in the suctioning MPCNL group were significantly less than those in the standard PCNL group. The average operation time, intrapelvic pressure, and amount of bleeding in the suctioning MPCNL group were better than those in the traditional MPCNL group. The suctioning MPCNL used one tract more frequently and 2 or 3 tracts less frequently than the standard MPCNL and traditional MPCNL groups. The stone-free rate by one surgery in the suctioning MPCNL group was significantly higher than that in standard PCNL and traditional MPNCL groups. CONCLUSIONS: Suctioning MPCNL using our patented system shows several advantages in treating renal staghorn calculi, including minimal invasion, shorter operation time, lower intrapelvic pressure, less bleeding and the need for a smaller number of -percutaneous tracts, and higher stone clearance rate by one -surgery.


Nephrolithotomy, Percutaneous/instrumentation , Staghorn Calculi/surgery , Surgical Equipment , Therapeutic Irrigation/instrumentation , Adult , China , Equipment Design , Female , Humans , Male , Middle Aged , Nephrolithotomy, Percutaneous/adverse effects , Operative Time , Postoperative Complications/etiology , Prospective Studies , Risk Factors , Staghorn Calculi/diagnostic imaging , Suction , Therapeutic Irrigation/adverse effects , Time Factors , Treatment Outcome
11.
Urology ; 116: 47-54, 2018 Jun.
Article En | MEDLINE | ID: mdl-29545046

OBJECTIVE: To investigate the effectiveness of modified mechanical percussion for eliminating upper urinary tract stone fragments after extracorporeal shock wave lithotripsy. MATERIALS AND METHODS: We assigned patients aged 18-60 years with upper urinary tract calculi to the modified mechanical percussion (trial) or observation (control) group. Kidney-ureter-bladder radiography and ultrasound were used for diagnostic evaluation. The primary outcome was the stone-expulsion rate (SER) at 6 hours. The first stone-expulsion time, the SER at 3, 12, and 24 hours, the stone-free rate, additional interventions, and adverse events (AEs) were recorded. RESULTS: A total of 120 patients underwent randomization: 60 for each group. The mean first stone-expulsion time in the trial and control groups was 6.75 and 13.58 hours, respectively (P = .001). The SERs at 3, 6, and 12 hours in the trial group were 51.8%, 75.4%, and 76.8%, respectively, which were higher than the control group (all P <.05). Among patients who expelled fragments within 6 hours, the stone-free rates were improved at 1 week (P = .002) and at 2 weeks (P = .000). Patients needed fewer additional interventions in the trial group (P = .035). AEs occurred in 42.9% (24 of 56) and 67.9% (38 of 56) of the patients in the trial and control groups, respectively (P = .008). Age, gender, stone size and location, and SER at 24 hours did not differ significantly among the groups. CONCLUSION: Modified mechanical percussion significantly improved SERs and accelerated stone passage after shock wave lithotripsy, resulting in a stone-free status with a lower risk of AEs and reduced need for additional interventions.


Kidney Calculi/therapy , Lithotripsy , Percussion/methods , Ureteral Calculi/therapy , Adult , Drainage, Postural , Equipment Design , Female , Humans , Lithotripsy/adverse effects , Lithotripsy/methods , Male , Middle Aged , Particle Size , Patient Positioning , Prospective Studies , Vibration , Young Adult
12.
Eur Urol ; 73(3): 385-391, 2018 Mar.
Article En | MEDLINE | ID: mdl-29137830

BACKGROUND: Recent large high-quality trials have questioned the clinical effectiveness of medical expulsive therapy using tamsulosin for ureteral stones. OBJECTIVE: To evaluate the efficacy and safety of tamsulosin for distal ureteral stones compared with placebo. DESIGN, SETTING, AND PARTICIPANTS: We conducted a double-blind, placebo-controlled study of 3296 patients with distal ureteral stones, across 30 centers, to evaluate the efficacy and safety of tamsulosin. INTERVENTION: Participants were randomly assigned (1:1) into tamsulosin (0.4mg) or placebo groups for 4 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point of analysis was the overall stone expulsion rate, defined as stone expulsion, confirmed by negative findings on computed tomography, over a 28-d surveillance period. Secondary end points included time to stone expulsion, use of analgesics, and incidence of adverse events. RESULTS AND LIMITATIONS: Among 3450 patients randomized between September 1, 2011, and August 31, 2013, 3296 (96%) were included in the primary analysis. Tamsulosin benefits from a higher stone expulsion rate than the placebo (86% vs 79%; p<0.001) for distal ureteral stones. Subgroup analysis identified a specific benefit of tamsulosin for the treatment of large distal ureteral stones (>5mm). Considering the secondary end points, tamsulosin-treated patients reported a shorter time to expulsion (p<0.001), required lower use of analgesics compared with placebo (p<0.001), and significantly relieved renal colic (p<0.001). No differences in the incidence of adverse events were identified between the two groups. CONCLUSIONS: Our data suggest that tamsulosin use benefits distal ureteral stones in facilitating stone passage and relieving renal colic. Subgroup analyses find that tamsulosin provides a superior expulsion rate for stones >5mm, but no effect for stones ≤5mm. PATIENT SUMMARY: In this report, we looked at the efficacy and safety of tamsulosin for the treatment of distal ureteral stones. We find that tamsulosin significantly facilitates the passage of distal ureteral stones and relieves renal colic.

13.
Article En | MEDLINE | ID: mdl-29186796

The main focus of this paper is to investigate the multiple attribute decision making (MADM) method under intuitionistic linguistic (IL) environment, based on induced aggregation operators and analyze possibilities for its application in low carbon supplier selection. More specifically, a new aggregation operator, called intuitionistic linguistic weighted induced ordered weighted averaging (ILWIOWA), is introduced to facilitate the IL information. Some of its desired properties are explored. A further generalization of the ILWIOWA, called intuitionistic linguistic generalized weighted induced ordered weighted averaging (ILGWIOWA), operator is developed. Furthermore, by employing the proposed operators, a MADM approach based on intuitionistic linguistic information is presented. Finally, an illustrative example concerning low carbon supplier selection and comparative analyses are conducted to demonstrate the effectiveness and practicality of the proposed approach.


Algorithms , Decision Making , Fuzzy Logic , Linguistics/methods , Linguistics/statistics & numerical data
14.
Adv Exp Med Biol ; 983: 217-229, 2017.
Article En | MEDLINE | ID: mdl-28639203

Small activating RNAs (saRNAs) are a class of artificially designed short duplex RNAs targeted at the promoter of a particular gene to upregulate its expression via a mechanism known as RNA activation (RNAa) and hold great promise for treating a wide variety of diseases including those undruggable by conventional therapies. The therapeutic benefits of saRNAs have been demonstrated in a number of preclinical studies carried out in different disease models including cancer. With many tumor suppressor genes (TSGs) downregulated due to either epigenetic mechanisms or haploinsufficiency resulting from deletion/mutation, cancer is an ideal disease space for saRNA therapeutics which can restore the expression of TSGs via epigenetic reprogramming. The p21WAF1/CIP gene is a TSG frequently downregulated in cancer and an saRNA for p21WAF1/CIP known as dsP21-322 has been identified to be a sequence-specific p21WAF1/CIP activator in a number of cancer types. In this chapter, we review preclinical development of medicinal dsP21-322 for cancer, especially prostate cancer and bladder cancer, and highlight its potential for further clinical development.


Prostatic Neoplasms/therapy , RNA, Double-Stranded/therapeutic use , RNA, Small Untranslated/therapeutic use , Urinary Bladder Neoplasms/therapy , Cell Line, Tumor , Cyclin-Dependent Kinase Inhibitor p21/genetics , Humans , Male , Promoter Regions, Genetic
15.
Onco Targets Ther ; 9: 787-95, 2016.
Article En | MEDLINE | ID: mdl-26937201

Prostate cancer (PC) is one of the leading causes of cancer death in men, and thus, finding new regulators is critical for PC therapy. Prostate and breast cancer overexpressed 1 (PBOV1) is overexpressed in breast, prostate, and bladder cancers, as it is upregulated in the serum of patients with PC, but the role of PBOV1 in PC has not been studied. In this article, we found that PBOV1 was indeed overexpressed in PC cells; PBOV1 overexpression promoted cell proliferation and colony formation ability and arrested cell cycle in the G0/G1 phase and tumorigenicity ability in vitro, whereas knockdown of PBOV1 reduced these effects. Further analysis of PBOV1 overexpression inhibited cell cycle inhibitors, P21 and P27, and increased the phosphorylation level of Rb and cyclin D1 expression, suggesting that PBOV1 promoted cell proliferation through promoting G1/S transition.

16.
Gene ; 576(1 Pt 3): 571-6, 2016 Jan 15.
Article En | MEDLINE | ID: mdl-26551397

Invasive progression is the major lethal cause of prostate cancer. In this study, we aimed to investigate the role of kindlin-2, an integrin-binding focal adhesion protein, in the regulation of invasiveness of prostate cancer. We found that downregulation of kindlin-2 using small interfering RNA (siRNA) technology significantly inhibited the invasion of PC-3 and DU-145 prostate cancer cells in a Matrigel Transwell assay. Conversely, overexpression of kindlin-2 promoted the invasiveness of prostate cancer cells. Kindlin-2 overexpression was found to activate nuclear factor (NF)-κB-dependent signaling and upregulate the expression of matrix metalloproteinase-9 (MMP-9) and MMP-2, whereas kindlin-2 silencing led to opposing effects on the expression of NF-κB and MMPs. Most importantly, kindlin-2-induced invasiveness was almost completely abolished by pretreatment with pyrrolidine dithiocarbamate (an inhibitor of NF-κB signaling) or co-transfection with MMP-9 or MMP-2 siRNA. Taken together, our data indicate that kindlin-2 promotes the invasiveness of prostate cancer cells largely through NF-κB-dependent upregulation of MMP-9 and MMP-2. Further studies are warranted to evaluate the significance of kindlin-2 as a therapeutic target for metastatic prostate cancer.


Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Membrane Proteins/physiology , NF-kappa B/metabolism , Neoplasm Invasiveness , Neoplasm Proteins/physiology , Prostatic Neoplasms/pathology , Up-Regulation , Humans , Male , Signal Transduction
17.
Sci Rep ; 5: 10905, 2015 Jun 05.
Article En | MEDLINE | ID: mdl-26046790

Several single-center studies have investigated whether narrow-band imaging (NBI) cystoscopy is more effective in detecting primary and recurrent non-muscle invasive bladder cancer (NMIBC) compared with white-light imaging (WLI) cystoscopy. In this study, we further evaluated the diagnostic value of NBI cystoscopy compared with WLI cystoscopy for primary NMIBC in a multi-center study. Suspected bladder cancer patients from 8 research centers received both NBI and WLI. Two experienced doctors in each center were responsible for the NBI and WLI assessments, respectively. The number of tumors and position of each tumor were recorded, and suspicious tissues were clamped and histologically examined. The sensitivity, specificity, and false-positive rate of NBI and WLI were evaluated. Of the 384 patients, 78 had a confirmed urothelial carcinoma (UC). The sensitivities of NBI and WLI were 97.70%, and 66.67%, respectively (P < 0.0001); the specificities were 50% and 25%, respectively; and the false positive rates were 50% and 75%, respectively. Based on 300 valid biopsy specimens, the NBI and WLI sensitivities were 98.80% and 75.45%, respectively (P < 0.0001). These results suggest that NBI has a high sensitivity and has superior early bladder tumor and carcinoma in situ (CIS) detection rates compared with WLI cystoscopy.


Urinary Bladder Neoplasms/diagnosis , Adolescent , Adult , Aged , Cystoscopy/methods , False Positive Reactions , Female , Humans , Male , Middle Aged , Prospective Studies , Sensitivity and Specificity , Young Adult
18.
PLoS One ; 10(6): e0130308, 2015.
Article En | MEDLINE | ID: mdl-26091007

OBJECTIVE: The influence of age on the performance of percent free prostate-specific antigen (%fPSA) in diagnosing prostate cancer (PCa) in East Asians is controversial. We tested the diagnostic performance of %fPSA in a multi-center biopsy cohort in China and identified the proper age-specific cutoff values to avoid unnecessary biopsies. METHODS: Consecutive patients with a prostate-specific antigen (PSA) level of 4.0-10.0 ng/ml or 10.1-20.0 ng/ml who underwent transrectal ultrasound-guided or transperineal prostate biopsy were enrolled from 22 Chinese medical centers from Jan 1, 2010 to Dec 31, 2013. The diagnostic accuracy of PSA and %fPSA was determined using the area under the receiver operating characteristic (ROC) curve (AUC). Age-specific cutoff values were calculated using ROC curve analysis. RESULTS: The median %fPSA was much lower in younger patients compared with older patients with a PSA level of 4.0-10.0 ng/ml or 10.1-20.0 ng/ml. The AUC of %fPSA was higher than PSA only in older patients. In patients aged 50 to 59 years, %fPSA failed to improve the diagnosis compared with PSA in these two PSA ranges. Age-specific cutoff values were 24%, 27% and 32% for patients aged 60-69, 70-79 and ≥80 years, respectively, to reduce unnecessary biopsies in men with PSA levels of 4.0-10.0 ng/ml to detect 90% of all PCa. CONCLUSIONS: The effectiveness of %fPSA is correlated with age in the Chinese population. Age-specific cutoff values would help avoid unnecessary biopsies in the Chinese population.


Kallikreins/blood , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Age Distribution , Age Factors , Aged , China , Humans , Male , Middle Aged , Prostatic Neoplasms/diagnosis , ROC Curve , Reference Values , Retrospective Studies
19.
Asian J Androl ; 17(6): 1017-21, 2015.
Article En | MEDLINE | ID: mdl-25926603

Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml-1 , however, it remains controversial whether %fPSA is effective in PSA range of 10.1-20.0 ng ml-1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer (PCa) and high-grade PCa (HGPCa) was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA>4.0 ng ml-1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA (%fPSA + PSA) was determined by the area under the receivers operating characteristic curve (AUC). %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0-10.0 ng ml-1 and 10.1-20.0 ng ml-1 , respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0-10.0 ng ml-1 and 10.1-20.0 ng ml-1 .


Biomarkers, Tumor/blood , Carcinoma/blood , Kallikreins/blood , Prostate-Specific Antigen/blood , Prostate/pathology , Prostatic Neoplasms/blood , Aged , Asian People , Biopsy, Large-Core Needle , Carcinoma/diagnosis , Carcinoma/pathology , China , Digital Rectal Examination , Endosonography , Humans , Image-Guided Biopsy , Male , Middle Aged , Organ Size , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathology , ROC Curve , Retrospective Studies , Sensitivity and Specificity
20.
Urologia ; 82(2): 102-5, 2015.
Article En | MEDLINE | ID: mdl-25791394

BACKGROUND: The flank-suspended position was adopted in percutaneous nephrolithotomy (PCNL), and haemodynamics, blood gas variables and subjective feelings were examined with an attempt to explore the effect of the operative position in PCNL on the body's inner environment and patient comfort. OBJECTIVE: The influence of the flank-suspended and prone position on haemodynamics, arterial blood gases and subjective feelings in patients receiving PCNL was examined. DESIGN, SETTING AND PARTICIPANTS: A total of 100 patients with kidney stones who underwent PCNL during January 2010 to January 2011 were divided into flank-suspended groups (n = 50) and prone groups (n = 50) at random in terms of the operative position. The blood pressure, heart rate, respiratory frequency and oxyhaemoglobin saturation and blood gas variables were determined at different time points (before the operation, after position change, 30 min after the start the operation and immediately after the operation). Visual analogue scale (VAS) scoring system was employed to define the posture comfort, dyspnoea and puncture-site pain 24 h postoperation in the patients. All the measures were compared between patients in different positions at different time points. STATISTICAL ANALYSIS: Paired t-test was employed in the comparison of measures detected at different time points in the same group. Two-group comparison was subjected to t-test. A p value less than 0.05 was considered statistically significant. RESULTS AND LIMITATIONS: The blood pressure was decreased within and after the operation in both groups, substantially in the prone group, significantly lower than that before the operation (p<0.05). No significant differences in the heart rate, respiratory frequency and oxyhaemoglobin saturation were noted among the different time points in the same group. Blood gas analysis showed that pH value and base excess were profoundly reduced within and after the operation in the two groups, significantly lower than those before the operation, and the decrease was most manifest in the prone group. There was no difference in the blood sodium and potassium among the different time points in each group. The flank-suspended group was superior to the prone group with regard to posture comfort and dyspnoea degree but not puncture-site pain 24 h postoperation. CONCLUSIONS: Flank-suspended and prone PCNL affects the haemodynamics, blood gas variables and subjective feelings of patients to a varying degree. The flank-suspended PCNL possesses advantages over prone PCNL such as little influence on haemodynamics and blood gas variables, satisfactory posture comfort, less dyspnoea and easy access to vital sign observation.


Emotions , Hemodynamics , Kidney Calculi/surgery , Nephrostomy, Percutaneous , Prone Position , Supine Position , Bicarbonates/blood , Blood Gas Analysis/methods , Carbon Dioxide/blood , Female , Humans , Kidney Calculi/blood , Male , Nephrostomy, Percutaneous/methods , Oxygen/blood , Patient Positioning/methods
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