Publications by authors named "Wanlong Tan"

59 Publications

A 23-Gene Classifier urine test for prostate cancer prognosis.

Clin Transl Med 2021 03;11(3):e340

Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen Urology Minimally Invasive Engineering Centre, Shenzhen, China.

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http://dx.doi.org/10.1002/ctm2.340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919118PMC
March 2021

Sequential administration of anti-PD-1 and anti-Tim-3 combined with an SA-GM-CSF-anchored vaccine overcomes adaptive immune resistance to reject established bladder cancer.

J Cancer 2021 2;12(7):2000-2009. Epub 2021 Feb 2.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.

Program death receptor-1 (PD-1) and T-cell immunoglobulin and mucin domain-containing protein-3 (Tim-3) play an important role in tumor immune evasion. PD-1 blockade could produce an effective anti-tumor effect but the response rate was low due to lacking of tumor infiltrating lymphocytes (TILs) and existing of other negative regulatory pathways. Streptavidin(SA)-GM-CSF surface-anchored tumor cells vaccine could induce specific anti-tumor immune response. However, this vaccine failed to induce regression of established tumor because it also up-regulated PD-1 expression on tumor cells dependent on IFNγ and up-regulated PD-1/Tim-3 expression on CD8 TILs. Subsets of CD8 TILs assay showed that PD-1 expression was closely associated with CD8 TILs exhaustion, and Tim-3 expression was closely correlated with secretion function but not proliferation of CD8 TILs. Sequential administration of anti-PD-1 and anti-Tim-3 could further improve the efficacy of SA-GM-CSF-anchored vaccine therapy, and tumor regression was noted in over 50%. This triple therapy improves the specific cytotoxic activity and decreased the apoptosis of CD8 TILs. These findings indicated that this triple therapy could induce a more robust anti-tumor immune response.
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http://dx.doi.org/10.7150/jca.44769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974521PMC
February 2021

HnRNP-F promotes the proliferation of bladder cancer cells mediated by PI3K/AKT/FOXO1.

J Cancer 2021 1;12(1):281-291. Epub 2021 Jan 1.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R.China.

Our previous study showed that heterogeneous nuclear ribonucleoprotein F (hnRNP-F) could induce epithelial-mesenchymal transition and metastasis in bladder cancer (BC), however, the role and mechanism of hnRNP-F in mediating the proliferative ability of BC cells remain unclear. HnRNP-F promoted the proliferation of BC cells by using BC cell lines and cell counting kit-8 (CCK8), colony formation and flow cytometry assays . Furthermore, the association of hnRNP-F with the phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT) signalling pathway was confirmed by western blotting after bioinformatic analysis. HnRNP-F expression was significantly decreased by treatment with the PI3K/AKT signalling pathway inhibitor LY294002, whereas hnRNP-F knockdown did not significantly affect PI3K or AKT expression, suggesting that hnRNP-F is likely a downstream target of the PI3K/AKT pathway. Forkhead box O1 (FOXO1) is a molecule downstream of PI3K/AKT and can be inhibited by phosphorylation. In addition, chromatin immunoprecipitation (ChIP) and luciferase reporter assays indicated that FOXO1 expression was negatively correlated with hnRNP-F expression as FOXO1 was found to bind to the promoter region of hnRNP-F mRNA and inhibit its transcription. To sum up, our findings suggest that hnRNP-F expression is regulated by the PI3K/AKT-mediated phosphorylation of FOXO1, with phosphorylation inhibiting FOXO1, which subsequently allows hnRNP-F to promote proliferation. This finding is a novel discovery in BC and could help reveal the mechanism of BC progression.
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http://dx.doi.org/10.7150/jca.50490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738822PMC
January 2021

Total Glucosides of Paeony Alleviate Cell Apoptosis and Inflammation by Targeting the Long Noncoding RNA XIST/MicroRNA-124-3p/ITGB1 Axis in Renal Ischemia/Reperfusion Injury.

Mediators Inflamm 2020 24;2020:8869511. Epub 2020 Nov 24.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.

Objective: Renal ischemia/reperfusion injury (RI/RI) is the main cause of acute kidney injury. Total glucosides of paeony (TGP) are a traditional Chinese medicine. This study was aimed at exploring the role of TGP in RI/RI and its underlying mechanism of action.

Methods: Rat RI/RI models were constructed by surgical operation. Serum creatinine (Scr) and blood urea nitrogen (BUN) were used to evaluate renal function. The levels of proinflammatory cytokines were detected by ELISA. RI/RI was simulated by hypoxia/reoxygenation (H/R) treatment in renal cells . The lncRNA XIST (XIST) expression was analyzed by qRT-PCR. Then, the viability and apoptosis of renal cells were detected by MTT and flow cytometry assay. Additionally, dual-luciferase reporter assay was used to determine the interactions among XIST, microRNA-124-3p (miR-124-3p), and ITGB1.

Results: TGP improved renal function and inhibited inflammatory responses after RI/RI. XIST expression was highly expressed in rat RI/RI models and H/R-treated renal cells, whereas treatment with TGP downregulated the XIST expression. Additionally, TGP increased viability and attenuated apoptosis and inflammation of H/R-treated renal cells via inhibiting XIST. Moreover, XIST was competitively bound to miR-124-3p, and ITGB1 was a target of miR-124-3p. miR-124-3p overexpression or ITGB1 inhibition rescued the reduction effect on viability and mitigated the promoting effects on cell apoptosis and inflammation caused by XIST overexpression in H/R-treated renal cells.

Conclusions: , TGP attenuated renal dysfunction and inflammation in RI/RI rats. , TGP inhibited XIST expression to modulate the miR-124-3p/ITGB1 axis, alleviating the apoptosis and inflammation of H/R-treated renal cells.
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http://dx.doi.org/10.1155/2020/8869511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710434PMC
November 2020

Development and validation of a 25-Gene Panel urine test for prostate cancer diagnosis and potential treatment follow-up.

BMC Med 2020 12 1;18(1):376. Epub 2020 Dec 1.

Department of Urology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China.

Background: Heterogeneity of prostate cancer (PCa) contributes to inaccurate cancer screening and diagnosis, unnecessary biopsies, and overtreatment. We intended to develop non-invasive urine tests for accurate PCa diagnosis to avoid unnecessary biopsies.

Methods: Using a machine learning program, we identified a 25-Gene Panel classifier for distinguishing PCa and benign prostate. A non-invasive test using pre-biopsy urine samples collected without digital rectal examination (DRE) was used to measure gene expression of the panel using cDNA preamplification followed by real-time qRT-PCR. The 25-Gene Panel urine test was validated in independent multi-center retrospective and prospective studies. The diagnostic performance of the test was assessed against the pathological diagnosis from biopsy by discriminant analysis. Uni- and multivariate logistic regression analysis was performed to assess its diagnostic improvement over PSA and risk factors. In addition, the 25-Gene Panel urine test was used to identify clinically significant PCa. Furthermore, the 25-Gene Panel urine test was assessed in a subset of patients to examine if cancer was detected after prostatectomy.

Results: The 25-Gene Panel urine test accurately detected cancer and benign prostate with AUC of 0.946 (95% CI 0.963-0.929) in the retrospective cohort (n = 614), AUC of 0.901 (0.929-0.873) in the prospective cohort (n = 396), and AUC of 0.936 (0.956-0.916) in the large combination cohort (n = 1010). It greatly improved diagnostic accuracy over PSA and risk factors (p < 0.0001). When it was combined with PSA, the AUC increased to 0.961 (0.980-0.942). Importantly, the 25-Gene Panel urine test was able to accurately identify clinically significant and insignificant PCa with AUC of 0.928 (95% CI 0.947-0.909) in the combination cohort (n = 727). In addition, it was able to show the absence of cancer after prostatectomy with high accuracy.

Conclusions: The 25-Gene Panel urine test is the first highly accurate and non-invasive liquid biopsy method without DRE for PCa diagnosis. In clinical practice, it may be used for identifying patients in need of biopsy for cancer diagnosis and patients with clinically significant cancer for immediate treatment, and potentially assisting cancer treatment follow-up.
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http://dx.doi.org/10.1186/s12916-020-01834-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706045PMC
December 2020

Urine DNA methylation assay enables early detection and recurrence monitoring for bladder cancer.

J Clin Invest 2020 12;130(12):6278-6289

Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China.

BACKGROUNDCurrent methods for the detection and surveillance of bladder cancer (BCa) are often invasive and/or possess suboptimal sensitivity and specificity, especially in early-stage, minimal, and residual tumors.METHODSWe developed an efficient method, termed utMeMA, for the detection of urine tumor DNA methylation at multiple genomic regions by MassARRAY. We identified the BCa-specific methylation markers by combined analyses of cohorts from Sun Yat-sen Memorial Hospital (SYSMH), The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) database. The BCa diagnostic model was built in a retrospective cohort (n = 313) and validated in a multicenter, prospective cohort (n = 175). The performance of this diagnostic assay was analyzed and compared with urine cytology and FISH.RESULTSWe first discovered 26 significant methylation markers of BCa in combined analyses. We built and validated a 2-marker-based diagnostic model that discriminated among patients with BCa with high accuracy (86.7%), sensitivity (90.0%), and specificity (83.1%). Furthermore, the utMeMA-based assay achieved a great improvement in sensitivity over urine cytology and FISH, especially in the detection of early-stage (stage Ta and low-grade tumor, 64.5% vs. 11.8%, 15.8%), minimal (81.0% vs. 14.8%, 37.9%), residual (93.3% vs. 27.3%, 64.3%), and recurrent (89.5% vs. 31.4%, 52.8%) tumors. The urine diagnostic score from this assay was better associated with tumor malignancy and burden.CONCLUSIONUrine tumor DNA methylation assessment for early diagnosis, minimal, residual tumor detection and surveillance in BCa is a rapid, high-throughput, noninvasive, and promising approach, which may reduce the burden of cystoscopy and blind second surgery.FUNDINGThis study was supported by the National Key Research and Development Program of China and the National Natural Science Foundation of China.
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http://dx.doi.org/10.1172/JCI139597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685755PMC
December 2020

Primary Urothelium Carcinoma of the Distal Urethra in a Male: Case Report and Literature Review.

Onco Targets Ther 2020 24;13:6011-6015. Epub 2020 Jun 24.

Department of Urology, Nan Fang Hospital, Southern Medical University, Guangzhou City, Guangdong Province 510515, People's Republic of China.

Male primary urethral urothelium carcinoma is a rare clinical case. Here, we detail a case of a 58-year-old man with primary urothelium carcinoma of the distal urethra treated in our hospital. The patient with a neoplasm inside the external urethral orifice for 2 years, which was previously diagnosed as condyloma acuminata, had received photodynamic therapy for 3 times, with initial symptoms of urinary stream bifurcation and dysuria. The exfoliative urine cytology showed negative. Cystoscopy showed a tumor growing around the distal urethra. Biopsy and immunohistochemistry revealed high-grade papillary urothelium carcinoma. The patient received partial urethrectomy, followed by urinary bladder irrigation chemotherapy with epirubicin postoperatively. The corpus spongiosum was invaded while the corpus cavernosa were not. Postoperative pathological examination showed high-grade invasive urothelium carcinoma. There is no evidence of tumor recurrence, metastasis or surgical complications during a 61-month follow-up period. Male primary urethral urothelium carcinoma is a rare clinical case with particular clinical and pathological characteristics. There are still no established treatment guidelines and should be studied further.
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http://dx.doi.org/10.2147/OTT.S252822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322166PMC
June 2020

Antitumor efficacy of interferon-γ-modified exosomal vaccine in prostate cancer.

Prostate 2020 08 19;80(11):811-823. Epub 2020 May 19.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: Exosomes secreted by tumor cells can be regarded as carriers of tumor-associated antigens and have potential value in tumor immunotherapy. The aim of this study was to evaluate the antitumor efficacy of a novel exosomal vaccine (interferon-γ [IFN-γ]-modified exosomal vaccine) in prostate cancer.

Methods: Prostate cancer cell-derived exosomes were used to prepare the exosomal vaccine using our protein-anchoring technique. The immunogenicity and therapeutic efficacy of the exosomes was evaluated by measuring the effects of the exosomal vaccine on M1 macrophage differentiation, the ability of macrophages to engulf the exosomes, the production of antibodies against exosomes, and tumor angiogenesis and metastasis, and tumor growth.

Results: The IFN-γ fusion protein was efficiently anchored on the surface of prostate cancer cell-derived exosomes and retained its bioactivity. The IFN-γ-exosomal vaccine increased the number of M1 macrophages, enhanced the ability of M1 macrophages to engulf RM-1 cell-derived exosomes, and induced the production of specific antibodies against exosomes. The exosomal vaccine downregulated the expression of vascular endothelial growth factor receptor 2 and attenuated the effect of exosomes in promoting tumor metastasis. The proportions of CD4 , CD8 , and IFN-γ CD8 T cells in the exosomal vaccine group were the highest among the four groups. Interestingly, the IFN-γ-exosomal vaccine decreased the percentage of Tregs and downregulated the expression of programed death-ligand 1 and indoleamine 2, 3-dioxygenase 1 in the tumor environment. The exosomal vaccine significantly inhibited tumor growth and prolonged the survival time of mice with prostate cancer. The exosomal and tumor cell vaccines had a good synergistic effect in promoting tumor immunity.

Conclusions: The novel exosomal vaccine induced an immune response that cleared prostate cancer cell-derived exosomes, thereby eliminating the regulatory effect of the exosomes. This study may provide experimental evidence for the use of exosomes as a therapeutic tool or target in immunotherapy for human prostate cancer.
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http://dx.doi.org/10.1002/pros.23996DOI Listing
August 2020

Yes-associated protein 1 promotes bladder cancer invasion by regulating epithelial-mesenchymal transition.

Int J Clin Exp Pathol 2019 1;12(3):1070-1077. Epub 2019 Mar 1.

Department of Urology, Nanfang Hospital, Southern Medical University Guangzhou, P. R. China.

Purpose: To investigate the expression of Yes-associated protein 1 (YAP1) in bladder cancer, and to study its role in regulating epithelial-mesenchymal transition in bladder cancer cells.

Material And Methods: The expression of YAP1, vimentin, and E-cadherin was detected by immunohistochemistry in bladder cancer and para-carcinoma tissues. The relation between expression levels and overall survival of patients was evaluated by Kaplan-Meier estimates. Furthermore, YAP1 expression was knocked down in T24 and UMUC3 bladder cancer through transfection with YAP1-targeted small interfering RNA (siRNA), and the impact on invasiveness and epithelial-mesenchymal transition was detected.

Results: Expression levels of YAP1 were higher in bladder cancer tissues, and increased YAP1 expression significantly correlated with poor patient outcomes and poor overall survival in bladder cancer patients. Furthermore, YAP1 siRNA significantly attenuated the invasion of bladder cancer cells and could reverse their epithelial-mesenchymal transition.

Conclusion: YAP1 appears to play an important role in bladder cancer progression and is highlighted as a novel potential therapeutic target.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945140PMC
March 2019

HnRNP-F promotes cell proliferation by regulating TPX2 in bladder cancer.

Am J Transl Res 2019 15;11(11):7035-7048. Epub 2019 Nov 15.

Department of Urology, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, P. R. China.

Heterogeneous nuclear ribonucleoprotein F (hnRNP-F) is crucial for gene expression and signal transduction as a tumor-promoting molecule with the ability to promote cell proliferation in various cancers. However, the role and mechanism of hnRNP-F in bladder cancer (BC) remain unclear. Therefore, we investigated the effect of hnRNP-F on the proliferation of BC cells and the potential mechanism. In this study, hnRNP-F was found to be upregulated in BC tissues and cells by western blotting. The knockdown of hnRNP-F could inhibit proliferation and delay cell cycle progression in EJ and UMUC-3 cells. Mechanistically, hnRNP-F was shown to bind to Targeting protein for Xenopus kinesin-like protein 2 (TPX2) by mass spectrometry and coimmunoprecipitation. Furthermore, Pearson correlation analysis showed that the expression of hnRNP-F was positively associated with that of TPX2 in BC tissues (<0.001, r=0.8180). Notably, TPX2 was correspondingly markedly decreased in cells upon hnRNP-F knockdown. In addition, the decrease in TPX2 after hnRNP-F knockdown further decreased cyclin D1 protein expression and evoked p21 protein expression, eventually resulting in cell cycle arrest and proliferation inhibition in BC cells. Moreover, the overexpression of TPX2 protein was found to reverse the effect of hnRNP-F knockdown on the cell cycle and cell proliferation in BC cells. In conclusion, these findings suggest that hnRNP-F could promote cell proliferation and drive cell cycle progression by regulating TPX2 in BC, which may serve as a potential target for the treatment of BC patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895536PMC
November 2019

Paraneoplastic limbic encephalitis cured with nephron-sparing surgery in a patient with clear cell renal cell carcinoma: a case report.

J Int Med Res 2019 Oct 12;47(10):5318-5322. Epub 2019 Sep 12.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P. R. China.

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http://dx.doi.org/10.1177/0300060519863524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833412PMC
October 2019

A co-expression network for differentially expressed genes in bladder cancer and a risk score model for predicting survival.

Hereditas 2019 9;156:24. Epub 2019 Jul 9.

1Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 China.

Background: Urothelial bladder cancer (BLCA) is one of the most common internal malignancies worldwide with poor prognosis. This study aims to explore effective prognostic biomarkers and construct a prognostic risk score model for patients with BLCA.

Methods: Weighted gene co-expression network analysis (WGCNA) was used for identifying the co-expression module related to the pathological stage of BLCA based on the RNA-Seq data retrieved from The Cancer Genome Atlas database. Prognostic biomarkers screened by Cox proportional hazard regression model and random forest were used to construct a risk score model that can predict the prognosis of patients with BLCA. The GSE13507 dataset was used as the independent testing dataset to test the performance of the risk score model in predicting the prognosis of patients with BLCA.

Results: WGCNA identified seven co-expression modules, in which the brown module consisted of 77 genes was most significantly correlated with the pathological stage of BLCA. Cox proportional hazard regression model and random forest identified TPST1 and P3H4 as prognostic biomarkers. Elevated TPST1 and P3H4 expressions were associated with the high pathological stage and worse survival. The risk score model based on the expression level of TPST1 and P3H4 outperformed pathological stage indicators and previously proposed prognostic models.

Conclusion: The gene co-expression network-based study could provide additional insight into the tumorigenesis and progression of BLCA, and our proposed risk score model may aid physicians in the assessment of the prognosis of patients with BLCA.
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http://dx.doi.org/10.1186/s41065-019-0100-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617625PMC
February 2020

A Novel Technique to Intelligently Monitor and Control Renal Pelvic Pressure during Minimally Invasive Percutaneous Nephrolithotomy.

Urol Int 2019 3;103(3):331-336. Epub 2019 Jul 3.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China,

Objective: To introduce a novel technique for intelligently monitoring and controlling renal pelvic pressure (RPP) in minimally invasive percutaneous nephrolithotomy (MPCNL) and to investigate its reliability and stability.

Materials And Methods: A total of 63 kidney stone patients (41 males and 22 females) were enrolled in the study. The average stone size was 3.7 ± 1.1 cm. The average age was 41.6 ± 15.6 years old. All patients underwent MPCNL under combined spinal and epidural anesthesia in prone position. A ureteral catheter connected to an invasive blood pressure monitor was retrogradely placed to measure renal pelvic outlet pressure. The MPCNL was performed with the aid of the patented device, including an irrigation and suctioning platform and a pressure-measuring suctioning sheath. On the platform, the RPP control value was set at -5 mm Hg, and the RPP warning value was set at 20 mm Hg. RPP was measured during the irrigation and suctioning period (ISP), and therapeutic period (TP) when the infusion flow was set at 300, 400, and 500 mL/min, respectively, for 5 min.

Results: Sixty-three patients successfully underwent the procedure without serious complications. The mean operative time was 67 min (range 31-127 min). Three patients had residual stones >2 mm in size. No statistical significance was observed between the renal pelvic outlet pressure, platform RPP values, and RPP control values for the 300, 400, and 500 mL/min groups during the ISP and TP (p > 0.05).

Conclusion: The patented devices including the platform and the sheath can reliably and stably monitor and control RPP in real time and within a safe range during MPCNL.
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http://dx.doi.org/10.1159/000501047DOI Listing
February 2020

Norcantharidin inhibits the DDR of bladder cancer stem-like cells through cdc6 degradation.

Onco Targets Ther 2019 7;12:4403-4413. Epub 2019 Jun 7.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.

Cancer stem cells (CSCs) are the main source of tumor resistance and recurrence. At present, the main treatment for patients with advanced or metastatic bladder cancer (BCa) is cisplatin-based combination chemotherapy. However, CSCs are not sensitive to DNA-damaging drugs due to their enhanced DNA damage response (DDR) activity. Bladder cancer stem cell-like cells (BCSLCs) were obtained by treating UMUC3 cells with cisplatin. The characteristics of the BCSLCs were identified by qPCR, flow cytometry, scratch wound-healing assays, transwell assays, tumorigenic ability experiments, Edu assays and Western blot assays in vivo. After BCSLCs were treated with norcantharidin (NCTD), the expression of Cdc6 and activation of the ATR-Chk1 pathway were detected by Western blotting. A subcutaneous tumor model in nude mice was successfully established to assess the anti-tumor efficacy of NCTD and cisplatin either alone or in combination in vivo. The tumor tissues were detected by immunohistochemistry. The derived BCSLCs showed higher expression of stemness markers, increased invasiveness, improved resistance to multiple chemotherapeutics, and higher tumorigenic capacity in vivo. The protein expression level of chromatin-binding Cdc6 was increased in BCSLCs; however, NCTD decreased the level of chromatin-binding Cdc6 and inhibited the activation of the ATR-Chk1 pathway, which ultimately led to reduction in DDR activity in BCSLCs. NCTD enhanced the killing effect of cisplatin on BCSLCs in vitro and vivo. NCTD combined with cisplatin enhanced cisplatin-induced DNA damage in BCSLCs. Long-term cisplatin treatment can enrich BCSLCs. However, NCTD enhanced the killing effect of cisplatin on BCSLCs in vitro and vivo. The mechanism is inhibiting the DDR activity by reducing the expression of chromatin-binding Cdc6.
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http://dx.doi.org/10.2147/OTT.S209907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560209PMC
June 2019

HnRNP-F regulates EMT in bladder cancer by mediating the stabilization of Snail1 mRNA by binding to its 3' UTR.

EBioMedicine 2019 Jul 18;45:208-219. Epub 2019 Jun 18.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, PR China. Electronic address:

Background: Heterogeneous nuclear ribonucleoprotein F (hnRNP-F) has been implicated in multiple cancers, suggesting its role in tumourigenesis, but the potential oncogenic role and mechanism of hnRNP-F in bladder cancer (BC) remain incompletely understood.

Methods: HnRNP-F was identified by proteomic methods. A correlation of hnRNP-F expression with prognosis was analysed in 103 BC patients. Then, we applied in vitro and in vivo methods to reveal the behaviours of hnRNP-F in BC tumourigenesis. Furthermore, the interaction between hnRNP-F and Snail1 mRNA was examined by RNA immunoprecipitation (RIP), and Snail1 mRNA stability was measured after treatment with actinomycin D. Finally, the binding domain between hnRNP-F and Snail1 mRNA was verified by constructing Snail1 mRNA truncations and mutants.

Finding: HnRNP-F is significantly upregulated in BC tissue, and its increased expression is associated with a poor prognosis in BC patients. HnRNP-F is necessary for tumour growth, inducing epithelial-mesenchymal transition (EMT) and metastasis in BC. The changes in Snail1 expression were positively correlated with hnRNP-F at both the mRNA and protein levels when hnRNP-F was silenced or enhanced, suggesting that Snail1 is likely a downstream target of hnRNP-F that mediates its effects on enhancing invasion, metastasis and EMT in BC. The overexpression of hnRNP-F caused an increase in the stability of Snail1 mRNA. Our RNA chip analysis revealed that hnRNP-F could combine with Snail1 mRNA, and we further demonstrated that hnRNP-F could directly bind to the 3' untranslated region (3' UTR) of Snail1 mRNA to enhance its stability.

Interpretation: Our findings suggest that hnRNP-F mediates the stabilization of Snail1 mRNA by binding to its 3' UTR, subsequently regulating EMT.
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http://dx.doi.org/10.1016/j.ebiom.2019.06.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642227PMC
July 2019

Adrenal Myelolipoma with Adrenocortical Adenoma Presenting with Hypertension Only.

J Coll Physicians Surg Pak 2019 Jun;29(6):S65-S67

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515-China.

Here, we present a case of a 25-year Chinese female who was diagnosed with non-functional adrenocortical adenoma containing myelolipoma with hypertension as the only symptom. Serum levels of cortisol, aldosterone, angiotensin I/II and renin activity were normal. Myelolipoma is a benign, non-functioning retroperitoneal tumour occurring predominantly in the adrenal gland and relatively uncommon. With the advancement of radiological studies, the incidental detection of myelolipoma has been noted. However, the coexistence of adrenal myelolipoma and adrenal adenoma still remains extremely rare. Though usually benign, the later may present with endocrine dysfunction, such as Cushing's syndrome, and requires proper management. Surgical resection is reserved for symptomatic tumours or large myelolipoma (>7 cm in size). The final diagnosis mainly relies on pathological examination. The left adrenal mass was completely removed via retroperitoneal laparoscopic approach. Postoperative recovery was uneventful and her blood pressure (BP) readings were normal. At 15 months follow-up, the patient was normotensive and there was no recurrence of tumour.
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http://dx.doi.org/10.29271/jcpsp.2019.06.S65DOI Listing
June 2019

Interferon-induced IFIT5 promotes epithelial-to-mesenchymal transition leading to renal cancer invasion.

Am J Clin Exp Urol 2019 18;7(1):31-45. Epub 2019 Feb 18.

Department of Urology, University of Texas Southwestern Medical Center Dallas, TX 75390, USA.

Interferon is known as a pleiotropic factor in innate immunity, cancer immunity and therapy. Despite an objective short-term response of interferon (IFN) therapy in renal cell carcinoma (RCC) patients, the potential adverse effect of IFN on RCC cells is not fully understood. In this study, we demonstrate that IFNs can enhance RCC invasion via a new mechanism of IFIT5-mediated tumor suppressor microRNA (miRNA) degradation resulted in the elevation of Slug and ZEB1 and epithelial-to-mesenchymal transition (EMT). Clinically, a significant upregulation of IFNγ signaling pathway (such as IFNGR1, IFNGR2, STAT1 and STAT2) is observed in RCC patients with metastatic disease. Overall, this study provides a new mechanism of action of IFN-elicited canonical pathway in regulating suppressor miRNAs. Most importantly, it highlights the potential pro-metastatic effect of IFNs, which could undermine the clinical applicability of IFNs for treating RCC patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420704PMC
February 2019

A higher circulating concentration of 25-hydroxyvitamin-D decreases the risk of renal cell carcinoma: a case-control study.

Int Braz J Urol 2019 May-Jun;45(3):523-530

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.

Objective: To investigate the relationship between vitamin D status, using circulating 25-hydroxyvitamin D [25 (OH) D], and renal cell carcinoma (RCC) risk in a case-control study, because the association between the two is unclear in China.

Materials And Methods: A total of 135 incident RCC cases were matched with 135 controls by age and sex. The blood samples were collected on the first day of hospitalization before surgery to measure plasma 25 (OH) D. Logistic regression analyses were used to calculate odds ratios (ORs) and 95% confi dence intervals (95% CIs) with adjustment for several confounders (e.g. age, gender, smoking and season of blood draw). Furthermore, the association of RCC with 25 (OH) D in units of 10 ng / mL as a continuous variable were also examined.

Results: The average plasma 25 (OH) D concentrations in RCC were signifi cantly lower compared with those of the controls (21.5 ± 7.4 ng / mL vs. 24.1 ± 6.6 ng / mL, respectively; P = 0.003). In the adjusted model, inverse associations were observed between circulating 25 (OH) D levels and RCC risk for 25 (OH) D insuffi ciency (20-30 ng / mL) with OR of 0.50 (95% CI: 0.29-0.88; P = 0.015) and a normal 25 (OH) D level (≥ 30 ng / mL) with OR of 0.30 (95% CI: 0.13-0.72; P = 0.007), compared with 25 (OH) D deficiency (< 20 ng / mL). Furthermore, results with 25 (OH) D as a linear variable indicated that each 10 ng / mL increment of plasma 25 (OH) D corresponded to a 12% decrease in RCC risk.

Conclusions: This case-control study on a Chinese Han population supports the protective effect of a higher circulating concentration of 25 (OH) against RCC, whether the confounding factors are adjusted or not.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2018.0186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786115PMC
July 2019

SIRT3 Inactivation Promotes Acute Kidney Injury Through Elevated Acetylation of SOD2 and p53.

J Surg Res 2019 01 31;233:221-230. Epub 2018 Aug 31.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. Electronic address:

Background: The deactivation of SIRT3, a novel deacetylase located in mitochondria, can aggravate multiple organ dysfunction. However, the role of SIRT3 and its downstream targets in ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) remain unknown.

Materials And Methods: I/R was reproduced in a rat model using a clamp placed on the left and right renal pedicles for 40 min. The rats were intraperitoneally injected with either the vehicle or a selective SIRT3 inhibitor (3-TYP) and scarified at different time points (4, 8, and 24 h after I/R). A portion of the renal tissue was extracted for histological analysis, and another portion was collected for the isolation of renal tubular epithelial cells for Western blotting, SOD2 and SIRT3 activity, cell apoptosis, and the determination of oxidative stress.

Results: The I/R-induced AKI model was successfully reproduced and SIRT3 activity was considerably reduced than control (sham operated) group, accompanied by increased acetylation of SOD2 and p53, as well as their elevated physical interaction in extracted mitochondrial protein (all P values < 0.05). Moreover, SIRT3 suppression by 3-TYP treatment (comparing with the vehicle treatment group) aggravated AKI, as evidenced by increased indicators of oxidative stress (increased mitochondrial red fluorescence MitoSOX and decreased reduced glutathione/oxidized glutathione ratio, all P values < 0.01).

Conclusions: The elevation of SOD2 and p53 protein acetylation in the mitochondria of renal tubular epithelial cells is an important signaling event in the pathogenesis of I/R-induced AKI. Thus, deacetylase SIRT3 may be an upstream regulator of both SOD2 and p53, and the SIRT3 deactivation may aggravate AKI.
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http://dx.doi.org/10.1016/j.jss.2018.07.019DOI Listing
January 2019

Overexpression of Tat-interacting protein 30 inhibits the proliferation, migration, invasion and promotes apoptosis in bladder cancer cells.

J Cancer Res Ther 2018 Sep;14(Supplement):S713-S718

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

Aims: Tat-interacting protein 30 (TIP30), a transcriptional repressor, possesses antitumor effect in different cancer cells. However, little is known about the function of TIP30 in bladder cancer till now.

Materials And Methods: A TIP30-overexpressing plasmid was transfected into the bladder cancer cells (T24). The cell cycle and apoptosis were detected by flow cytometry. The cell proliferation was analyzed using the cell counting kit-8 assay. The migrative and invasive abilities of T24 cells were measured by the transwell assay. The expression of TIP30, cell cycle proteins, migration-related proteins, and cell apoptosis-related proteins was assessed by Western blotting.

Results: The cell proliferation, migration, and invasion of T24 cells were inhibited by overexpression of TIP30. Moreover, the rate of cell apoptosis was increased by the overexpression of TIP30. The expression of cell cycle proteins, phosphorylated EGFR, p-Akt, Bcl-2, cyclin D, cyclin E), migration-related proteins (matrix metalloproteinases 2 [MMP2], MMP6, MMP9), were downregulated, and cell apoptosis-related proteins (bax, cleaved caspase3) were upregulated.

Conclusions: These results suggest that TIP30, as a tumor suppressor in the bladder cancer, might be served as a target in cancer therapies in the future.
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http://dx.doi.org/10.4103/0973-1482.206869DOI Listing
September 2018

Suctioning flexible ureteroscopic lithotripsy in the oblique supine lithotomy position and supine lithotomy position: a comparative retrospective study.

Minerva Urol Nefrol 2018 Dec 23;70(6):612-616. Epub 2018 Jul 23.

Department of Urology, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, China -

Background: Flexible ureteroscopy is very valuable for treating upper urinary tract calculi. However, no report has yet compared the clinical outcomes of flexible ureteroscopy performed on patients in different body positions. Therefore, we compared the safety and efficacy of suctioning flexible ureteroscopic lithotripsy with automatic control of renal pelvic pressure in the oblique supine lithotomy position and supine lithotomy position.

Methods: A total of 82 patients with kidney calculi performed by suctioning flexible ureteroscopic lithotripsy with automatic control of renal pelvic pressure were retrospectively analyzed in single center. Group 1 included 47 patients treated via suctioning flexible ureteroscopy in the oblique supine lithotomy position. Group 2 included 35 patients treated in the supine lithotomy position. There were no significant differences in age, gender, or comorbidity rate between the two groups before surgery (P>0.05). Operative time, stone-free rate at postoperative day 30, renal pelvic pressure, postoperative complications, and length of hospital stay were compared between the two groups.

Results: Flexible ureteroscopy was successful after the first surgery in 73 patients and successful in the other nine patients after the placement of an indwelling double-J stent for 2 weeks. Compared to group 2, a significantly greater stone-free rate on postoperative day 30 and a significantly shorter operative time were noted in the group 2 (85.7% vs. 97.9%; 31.81±2.2 min vs. 23.4±14.9 min, P<0.05). We found no between-group difference in complication rates of Clavien grade I or Clavien grade II, renal pelvic pressure, and length of hospital stay (all P>0.05).

Conclusions: Suctioning flexible ureteroscopic lithotripsy with automatic control of renal pelvic pressure in the oblique supine lithotomy position was safe and more effective than in the supine lithotomy position.
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http://dx.doi.org/10.23736/S0393-2249.18.03144-2DOI Listing
December 2018

PD-1 blockade enhances the antitumor efficacy of GM-CSF surface-modified bladder cancer stem cells vaccine.

Int J Cancer 2018 05 26;142(10):2106-2117. Epub 2017 Dec 26.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Eliminating cancer stem cells (CSCs) is a key issue in eradicating tumor. The streptavidin-granulocyte-macrophage-colony stimulating factor (SA-GM-CSF) surface-modified bladder CSCs vaccine previously developed using our protein-anchor technology could effectively induce specific immune response for eliminating CSCs. However, program death receptor-1 (PD-1)/program death ligand 1 (PD-L1) signaling in tumor microenvironment results in tumor-adaptive immune resistance. Although the CSCs vaccine could increase the number of CD8 T cells, a part of these CD8 T cells expressed PD-1. Moreover, the CSCs vaccine upregulated the PD-L1 expression of tumor cells, resulting in immune resistance. Adding PD-1 blockade to the CSCs vaccine therapy increased the population of CD4 , CD8 and CD8 IFN-γ but not CD4 Foxp3 T cells and induced the highest production of IFN-γ. PD-1 blockade could effectively enhance the functions of tumor-specific T lymphocytes generated by the CSCs vaccine. This combination therapy improved the cure rate among mice and effectively protected the mice against a second CSCs cell challenge, but not a RM-1 cell challenge. These results indicate that PD-1 blockade combined with the GM-CSF-modified CSCs vaccine effectively induced a strong and specific antitumor immune response against bladder cancer.
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http://dx.doi.org/10.1002/ijc.31219DOI Listing
May 2018

Inflammation and Fibrosis in Perirenal Adipose Tissue of Patients With Aldosterone-Producing Adenoma.

Endocrinology 2018 01;159(1):227-237

Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

The prevalence of primary aldosteronism is much higher than previously thought. Recent studies have shown that primary aldosteronism is related to a higher risk of cardiovascular events. However, the underlying mechanism is not yet clear. Here we investigate the characteristics, including inflammation, fibrosis, and adipokine expression, of adipose tissues from different deposits in patients with aldosterone-producing adenoma (APA). Inflammation and fibrosis changes were evaluated in perirenal and subcutaneous adipose tissues obtained from patients with APA (n = 16), normotension (NT; n = 10), and essential hypertension (EH; n = 5) undergoing laparoscopic surgery. We also evaluated the effect of aldosterone in isolated human perirenal adipose tissue stromal vascular fraction (SVF) cells and investigated the effect of aldosterone in mouse 3T3-L1 and brown preadipocytes. Compared with the EH group, significantly higher levels of interleukin-6 (IL-6) and tumor necrosis factor-α messenger RNA (mRNA) and protein were observed in perirenal adipose tissue of patients with APA. Expression of genes related to fibrosis and adipogenesis in perirenal adipose tissue was notably higher in patients with APA than in patients with NT and EH. Aldosterone significantly induced IL-6 and fibrosis gene mRNA expression in differentiated SVF cells. Aldosterone treatment enhanced mRNA expression of genes associated with inflammation and fibrosis and stimulated differentiation of 3T3-L1 and brown preadipocytes. In conclusion, these data indicate that high aldosterone in patients with APA may induce perirenal adipose tissue dysfunction and lead to inflammation and fibrosis, which may be involved in the high risk of cardiovascular events observed in patients with primary aldosteronism.
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http://dx.doi.org/10.1210/en.2017-00651DOI Listing
January 2018

PD-1/PD-L1 blockade enhances the efficacy of SA-GM-CSF surface-modified tumor vaccine in prostate cancer.

Cancer Lett 2017 10 8;406:27-35. Epub 2017 Aug 8.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address:

Program death receptor-1 (PD-1)/program death ligand 1 (PD-L1) signaling plays an important role in tumor adaptive immune resistance. The streptavidin-granulocyte-macrophage colony stimulating factor (SA-GM-CSF) surface-modified tumor cells vaccine developed through our novel protein-anchor technology could significantly promote the activation of dendritic cells. Although GM-CSF vaccine could significantly increase the number of tumor-specific CD8T-cells, the majority of these CD8T-cells expressed PD-1. Moreover, GM-CSF vaccine up-regulated the PD-L1 expression of tumor cells, resulting in immune resistance. Adding PD-1/PD-L1 blockade to GM-CSF vaccine therapy could significantly increase the population of CD4 T, CD8 T and CD8 IFN-γ T but not CD4 Foxp3 T-cells and induced the highest production of IFN-γ. PD-1/PD-L1 blockade could effectively rescue the tumor-specific T lymphocytes generated by the GM-CSF vaccine, resulting in consistent tumor rejection. Taken together, PD-1/PD-L1 blockade combined with SA-GM-CSF-modified vaccine could effectively induce a strong specific antitumor immune response against prostate cancer.
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http://dx.doi.org/10.1016/j.canlet.2017.07.029DOI Listing
October 2017

SATB1 promotes epithelial-mesenchymal transition and metastasis in prostate cancer.

Oncol Lett 2017 Apr 22;13(4):2577-2582. Epub 2017 Feb 22.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Special AT-rich sequence-binding protein-1 (SATB1) is associated with cancer progression and poor clinical outcome. The present study aims to evaluate whether SATB1 affects the biological behaviors of prostate cancer (PCa), and furthermore, to elucidate whether this effect works through the epithelial-mesenchymal transition (EMT) pathway. Firstly, the expression of SATB1 was investigated in a series of PCa tissues as well as in a panel of PCa cell lines. Cell proliferation, migration and invasion were evaluated in SATB1 knockdown and overexpressed PCa cell lines by MTT and Transwell assays. The results showed that the expression of SATB1 was markedly upregulated in PCa tissues and all PCa cell lines (P<0.001). Ectopic expression of SATB1 promoted PCa cell proliferation and migration. Knockdown of SATB1 repressed the ability of cell proliferation and migration of PCa cells. In addition, inhibition of SATB1 could reverse the EMT processes through upregulation of E-cadherin and downregulation of vimentin. The present study provided evidence that SATB1 may act as a potential therapeutic target in PCa patients.
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http://dx.doi.org/10.3892/ol.2017.5765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403494PMC
April 2017

Association of smoking status with prognosis in bladder cancer: A meta-analysis.

Oncotarget 2017 Jan;8(1):1278-1289

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R.China.

There is considerable controversy regarding the association between smoking and prognosis in surgically treated bladder cancer. The present meta-analysis was performed to quantify the role of smoking status in bladder cancer recurrence, progression and patient survival by pooling the available previous data. Pubmed, Embase and the Cochrane Library databases were searched for eligible studies published prior to April 2016. Random and fixed effects models were used to calculate the summary relative risk estimates (SRRE). A total of 10,192 patients from 15 studies were included in the meta-analysis. There was evidence of positive associations between current smoking and the risk of recurrence (SRRE=1.23; 95% CI, 1.05-1.45) and mortality (SRRE=1.28; 95% CI, 1.07-1.52) in bladder cancer. Furthermore, former smoking had positive associations with bladder cancer recurrence (SRRE=1.22; 95% CI, 1.09-1.37) and mortality (SRRE=1.20; 95% CI, 1.03-1.41). However, there was no significant association between bladder cancer progression risk and current (SRRE=1.11; 95% CI, 0.71-1.75) or previous smoking (SRRE=1.16; 95% CI, 0.92-1.46). The findings indicate that current and former smoking increase the risk of recurrence and mortality in patients with bladder cancer. However, due to the nonrandomized and retrospective nature of the current study, patients may be prone to potential selection bias. Prospective and larger epidemiological studies with a longer follow-up are required to confirm these findings.
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http://dx.doi.org/10.18632/oncotarget.13606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352054PMC
January 2017

Impact of surgical margin status on the outcome of bladder cancer treated by radical cystectomy: a meta-analysis.

Oncotarget 2017 Mar;8(10):17258-17269

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China.

Data regarding the association between surgical margin status and the outcome of bladder cancer treated by radical cystectomy (RC) are conflicting. Therefore, the present meta-analysis was performed to assess the associations between the outcomes of bladder cancer, in terms of recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS), and the presence of positive surgical margins versus negative surgical margins following treatment with RC. Research articles published prior to April 2016 were identified from Pubmed, Embase and the Cochrane Library databases. A total of 36 articles were included, with a sample size of 38,384 bladder cancer patients. Of these, 4,354 patients were reported to have positive surgical margins. Significant associations were detected between positive surgical margins following RC and unfavorable RFS [summary relative risk estimate (SRRE), 1.63; 95% confidence interval (CI), 1.46-1.83; P = 0.105], CSS (SRRE, 1.82; 95% CI, 1.63-2.04; P = 0.001) and OS (SRRE, 1.68; 95% CI, 1.58-1.80; P = 0.805), by fixed or random effects models. The findings were consistent independently of age, sample size, publication year, follow-up duration, study type and geographical region. In summary, the present findings demonstrate that the presence of positive surgical margins is associated with poor survival outcomes in bladder cancer following RC, indicating that avoidance of positive surgical margins during surgery is helpful to improve the prognosis of patients with bladder cancer.
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http://dx.doi.org/10.18632/oncotarget.12907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370038PMC
March 2017

Cdc6 contributes to cisplatin-resistance by activation of ATR-Chk1 pathway in bladder cancer cells.

Oncotarget 2016 Jun;7(26):40362-40376

Institute of Biotherapy, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.

High activation of DNA damage response is implicated in cisplatin (CDDP) resistance which presents as a serious obstacle for bladder cancer treatment. Cdc6 plays an important role in the malignant progression of tumor. Here, we reported that Cdc6 expression is up-regulated in bladder cancer tissues and is positively correlated to high tumor grade. Cdc6 depletion can attenuate the malignant properties of bladder cancer cells, including DNA replication, migration and invasion. Furthermore, higher levels of chromatin-binding Cdc6 and ATR were detected in CDDP-resistant bladder cancer cells than in the parent bladder cancer cells. Intriguingly, down-regulation of Cdc6 can enhance sensitivity to CDDP both in bladder cancer cells and CDDP-resistant bladder cancer cells. Cdc6 depletion abrogates S phase arrest caused by CDDP, leading to aberrant mitosis by inactivating ATR-Chk1-Cdc25C pathway. Our results indicate that Cdc6 may be a promising target for overcoming CDDP resistance in bladder cancer.
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http://dx.doi.org/10.18632/oncotarget.9616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5130013PMC
June 2016

A greater number of dissected lymph nodes is associated with more favorable outcomes in bladder cancer treated by radical cystectomy: a meta-analysis.

Oncotarget 2016 Sep;7(38):61284-61294

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P. R. China.

The optimal extent of lymph node dissection (LND) is currently not established, and the debate regarding the association between the number of dissected nodes and the outcomes of bladder cancer treated by radical cystectomy (RC) is still ongoing. Therefore, the present meta-analysis was performed to clarify this potential relationship. Eligible studies were retrieved via an electronic search for studies published up to April 2016, and by manual review of the references. A total of 25 cohort studies involving 41,400 bladder cancer patients who underwent RC were included. The summary relative risk estimates (SRRE) based on the highest compared with the lowest categories of LND were estimated by variance-based meta-analysis. Heterogeneity among the study results was explored through stratified analyses. Overall, bladder cancer patients with the highest category of LND had 28%, 34% and 36% reduced risks, corresponding to overall survival (SRRE = 0.72; 95% CI, 0.64-0.80), cancer-specific survival (SRRE = 0.66; 95% CI, 0.54-0.80) and recurrence-free survival (SRRE = 0.64; 95% CI, 0.50-0.82), respectively, compared with patients with the lowest category of LND. In summary, the patients with a greater number of dissected lymph nodes had statistically significant survival advantages in terms of the outcomes of bladder cancer following RC. The number of dissected lymph nodes could be an independent prognostic factor for bladder cancer. These findings need to be validated in prospective and larger epidemiological studies with a longer follow-up period.
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http://dx.doi.org/10.18632/oncotarget.11343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308651PMC
September 2016

The increased excretion of urinary orosomucoid 1 as a useful biomarker for bladder cancer.

Am J Cancer Res 2016 15;6(2):331-40. Epub 2016 Jan 15.

Department of Urology, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, P. R. China.

Improving the early detection rate and prediction of bladder cancer remains a great challenge in management of this disease. To examine the value of urinary orosomucoid 1 (ORM1) for the early detection and surveillance of bladder cancer, two-dimensional differential gel electrophoresis (2-DE) and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF/TOFMS) were applied to identify the differently expressed proteins in urine between bladder cancer and healthy controls. Thirteen different proteins including ORM1 were identified. After verification by western blotting, the ORM1 expressions were quantified in 186 urine samples by enzyme-linked immunosorbent assay (ELISA) correcting for creatinine expression. ELISA quantification showed the urinary ORM1-Cr was found to be higher in bladder cancer patients compared to controls and benign cases (7172.23±3049.67 versus 2243.16±969.01, 2493.48±830.37 ng/ml, respectively, P<0.0001). Furthermore, the pearson correlation analysis indicated that urinary ORM1 had high positive correlation with the pathology classification of bladder cancer. Receiver operating characteristic (ROC) analysis was used to calculate the cut-off value for early diagnosis of bladder cancer, and rendered an optimum cut-off value of 3912.97 ng/mg corresponding to 91.96% sensitivity and 94.34% specificity. Moreover, a cut-off value with 7351.28 ng/mg was utilized to distinguish infiltrating urothelial carcinoma from bladder cancer patients corresponding to 91.89% sensitivity and 90.67% specificity. In conclusion, our findings suggested the elevated urinary ORM1 could be a useful biomarker for bladder cancer. Further research is warranted to elucidate the pathogenic mechanisms of elevated ORM1.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859664PMC
May 2016
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