Publications by authors named "Muwen Wang"

26 Publications

  • Page 1 of 1

LncRNA PlncRNA-1 accelerates the progression of prostate cancer by regulating PTEN/Akt axis.

Aging (Albany NY) 2021 Apr 13;13(8):12113-12128. Epub 2021 Apr 13.

Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China.

Long non-coding RNAs are key regulators of tumor development and progression, with the potential to be biomarkers of tumors. This study aimed to explore the role of PlncRNA-1 in the progression of prostate cancer (PCa). We found that PlncRNA-1 was up-regulated in 85.29% of PCa tissues and could predict the T stage of PCa patients to a certain extent. Results showed that inhibition of PlncRNA-1 expression potentially promoted cell apoptosis, suppressed the proliferation, migration, and invasion of cells, and triggered G2/M cycle arrest and . PlncRNA-1 was mainly localized in the nucleus and PlncRNA-1 expression and phosphatase and tensin homologue (PTEN) expression were negatively correlated. Mechanistically, knockdown of PlncRNA-1 increased expression levels of PTEN protein and phosphorylated PTEN protein, and decreased expression levels of Akt protein and phosphorylated Akt protein. Rescue experiments demonstrated that PTEN inhibitors abolished the changes in PTEN/Akt pathway caused by PlncRNA-1 interference. PlncRNA-1 can promote the occurrence and development of PCa via the PTEN/Akt pathway. PlncRNA-1 may, therefore, be a new candidate target for the treatment of PCa.
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http://dx.doi.org/10.18632/aging.202919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109094PMC
April 2021

RPN2 Predicts Poor Prognosis and Promotes Bladder Cancer Growth and Metastasis via the PI3K-Akt Pathway.

Onco Targets Ther 2021 3;14:1643-1657. Epub 2021 Mar 3.

Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.

Background: Ribophorin II (RPN2) is a highly conserved glycoprotein involved in the N-linked glycosylation of multiple proteins. RPN2 was reported to be associated with malignant phenotype in several tumors. However, the function of RPN2 in bladder cancer (BCa) remains unclear.

Methods: Expression of RPN2 in BCa and adjacent tissues was compared by bioinformatics analysis, immunohistochemistry, and Western blotting. qRT-PCR was performed to explore the correlation between RPN2 expression and various clinical features in 38 patients. We assessed the effects of RPN2 on the biological activity of BCa both in vitro and in vivo, and explored its potential mechanisms based on gene set enrichment analysis (GSEA).

Results: We found that RPN2 was highly expressed in human BCa compared with normal adjacent tissues. There was a significant positive correlation between higher RPN2 mRNA levels and tumor T stage, lymph node (LN) metastasis and the degree of pathological differentiation in 38 patients with BCa. We further demonstrated that RPN2 silencing inhibited the growth and metastasis of BCa both in vitro and in vivo. Western blotting revealed that RPN2 knockdown suppressed epithelial-mesenchymal transition (EMT) and inhibited the PI3K-Akt pathway.

Conclusion: These data suggest that RPN2 functions as an oncogene to promote tumor development and is a promising prognostic factor and therapeutic target in BCa.
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http://dx.doi.org/10.2147/OTT.S300480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953128PMC
March 2021

Berbamine Suppresses the Progression of Bladder Cancer by Modulating the ROS/NF-B Axis.

Oxid Med Cell Longev 2021 13;2021:8851763. Epub 2021 Jan 13.

Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China.

Berbamine (BBM), one of the bioactive ingredients extracted from plants, has attracted intensive attention because of its significant antitumor activity against various malignancies. However, the exact role and potential molecular mechanism of berbamine in bladder cancer (BCa) remain unclear. In the present study, our results showed that berbamine inhibited cell viability, colony formation, and proliferation. Additionally, berbamine induced cell cycle arrest at S phase by a synergistic mechanism involving stimulation of P21 and P27 protein expression as well as downregulation of CyclinD, CyclinA2, and CDK2 protein expression. In addition to suppressing epithelial-mesenchymal transition (EMT), berbamine rearranged the cytoskeleton to inhibit cell metastasis. Mechanistically, the expression of P65, P-P65, and P-IB was decreased upon berbamine treatment, yet P65 overexpression abrogated the effects of berbamine on the proliferative and metastatic potential of BCa cells, which indicated that berbamine attenuated the malignant biological activities of BCa cells by inhibiting the NF-B pathway. More importantly, berbamine increased the intracellular reactive oxygen species (ROS) level through the downregulation of antioxidative genes such as Nrf2, HO-1, SOD2, and GPX-1. Following ROS accumulation, the intrinsic apoptotic pathway was triggered by an increase in the ratio of Bax/Bcl-2. Furthermore, berbamine-mediated ROS accumulation negatively regulated the NF-B pathway to a certain degree. Consistent with our in vitro results, berbamine successfully inhibited tumor growth and blocked the NF-B pathway in our xenograft model. To summarize, our data demonstrated that berbamine exerts antitumor effects via the ROS/NF-B signaling axis in bladder cancer, which provides a basis for further comprehensive study and presents a potential candidate for clinical treatment strategies against bladder cancer.
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http://dx.doi.org/10.1155/2021/8851763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817266PMC
January 2021

Hypomethylation of PlncRNA-1 promoter enhances bladder cancer progression through the miR-136-5p/Smad3 axis.

Cell Death Dis 2020 12 7;11(12):1038. Epub 2020 Dec 7.

Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, China.

Apart from being potential prognostic biomarkers and therapeutic targets, long non-coding RNAs (lncRNAs) modulate the development and progression of multiple cancers. PlncRNA-1 is a newly discovered lncRNA that exhibits the above properties through multiple regulatory pathways. However, the clinical significance and molecular mechanisms of PlncRNA-1 in bladder cancer have not been established. PlncRNA-1 was found to be overexpressed in 71.43% of bladder cancer tissues. Moreover, the expression level correlated with tumor invasion, T stage, age, and number of tumors, but not with gender, recurrent status, preoperative treatment, pathological grade, and tumor size. The expression level of PlncRNA-1 can, to a certain extent, be used as a predictor of the degree of tumor invasion and T stage among BC patients. Inhibiting PlncRNA-1 expression impaired the proliferation, migration, and invasion of T24 and 5637 bladder cancer cells in vitro and in vivo. Specifically, PlncRNA-1 promoter in BC tissues was found to be hypomethylated at position 131 (36157603 on chromosome 21). PlncRNA-1 promoter hypomethylation induces the overexpression of PlncRNA-1. In addition, PlncRNA-1 modulated the expression of smad3 and has-miR-136-5p (miR-136). Conversely, miR-136 regulated the expression of PlncRNA-1 and smad3. PlncRNA-1 mimics competitive endogenous RNA (ceRNA) in its regulation of smad3 expression by binding miR-136. Rescue analysis further revealed that modulation of miR-136 could reverse the expression of smad3 and epithelial-mesenchymal transition (EMT) marker proteins impaired by PlncRNA-1. In summary, PlncRNA-1 has important clinical predictive values and is involved in the post-transcriptional regulation of smad3. The PlncRNA-1/miR-136/smad3 axis provides insights into the regulatory mechanism of BC, thus may serve as a potential therapeutic target and prognostic biomarker for cancer.
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http://dx.doi.org/10.1038/s41419-020-03240-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721747PMC
December 2020

Investigation of acute, subacute and subchronic toxicities of anthocyanin derived acylation reaction products and evaluation of their antioxidant activities in vitro.

Food Funct 2020 Dec 7;11(12):10954-10967. Epub 2020 Dec 7.

School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China.

Previously, anthocyanins were successfully acylated with lauric acid using Novozym 435 lipase, and the corresponding products were confirmed to have higher stability. As novel synthetic compounds, their toxicological safety has not been evaluated. Therefore, acute, subacute and subchronic toxicities of anthocyanin-lauric acid derivatives (ALDs) were investigated while their antioxidant activities were also evaluated in vitro. The acute toxicity results showed that the 50% lethal dose (LD) of ALDs in mice was >10 g kg. Subsequently, the subacute toxicity test was conducted by oral administration of ALDs at doses of 0.63, 1.25 and 2.50 g kg for 28 days. No adverse effect of ALDs on body weight, food/water intake, organ coefficient and histology was observed. Though there were some fluctuations in AST and ALT, the tested biochemical parameters were maintained within the normal ranges. The subchronic toxicity test results demonstrated that less than 0.60 g of ALDs per kg BW intake did not affect mortality, body weight, food/water intake, gross pathology, histology, hematology and serum biochemistry. Furthermore, cyanidin-3-(6''-dodecanoyl)-glucoside, the main component of ALDs, had a beneficial reducing power and a strong DPPH˙, ABTS˙, and O˙ scavenging activity. This study provides an imperative reference to the safety of ALDs, suggesting their application as novel colorants or antioxidants in food and therapeutics.
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http://dx.doi.org/10.1039/d0fo01478hDOI Listing
December 2020

Roles of Reactive Oxygen Species in Biological Behaviors of Prostate Cancer.

Biomed Res Int 2020 29;2020:1269624. Epub 2020 Sep 29.

Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China.

Prostate cancer (PCa), known as a heterogenous disease, has a high incidence and mortality rate around the world and seriously threatens public health. As an inevitable by-product of cellular metabolism, reactive oxygen species (ROS) exhibit beneficial effects by regulating signaling cascades and homeostasis. More and more evidence highlights that PCa is closely associated with age, and high levels of ROS are driven through activation of several signaling pathways with age, which facilitate the initiation, development, and progression of PCa. Nevertheless, excessive amounts of ROS result in harmful effects, such as genotoxicity and cell death. On the other hand, PCa cells adaptively upregulate antioxidant genes to detoxify from ROS, suggesting that a subtle balance of intracellular ROS levels is required for cancer cell functions. The current review discusses the generation and biological roles of ROS in PCa and provides new strategies based on the regulation of ROS for the treatment of PCa.
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http://dx.doi.org/10.1155/2020/1269624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538255PMC
May 2021

Kinetics of Enzymatic Synthesis of Cyanidin-3-Glucoside Lauryl Ester and Its Physicochemical Property and Proliferative Effect on Intestinal Probiotics.

Biology (Basel) 2020 Aug 4;9(8). Epub 2020 Aug 4.

School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China.

The interest in anthocyanins used in food, cosmetic, and pharmaceutical industries has increased the research in order to improve their stability while maintaining bioactivity. In this work, cyanidin-3-glucoside lauryl ester (Cy3glc-C12) was enzymatically synthesized, using Novozym 435 as a catalyst, as well as to obtain a kinetic model for the bioprocess. Its liposolubility, UV-VIS absorbance property, thermostability, and potential proliferative effect on intestinal probiotics were also studied. The maximum conversion yield (68.7 ± 2.1%) was obtained with a molar ratio (substrate:donor) of 1:56, 435 16.5 g/L Novozym, temperature of 56 °C, and a time of 28 h via the acylation occurred at 6''-OH position of the glucoside. The kinetics of the reaction is consistent with a ping-pong bi-bi mechanism and the parameters of the respective kinetic equations are reported. Compared with native Cy3glc, the liposolubility, pH resistivity and thermostability of Cy3glc-C12 were significantly improved. The growth kinetics of and was established based on the Logistic equation, and Cy3glc-C12 could promote their proliferation especially during the logarithmic growth, in which lower pH and more bacteria population were found compared with those of media without anthocyanins. This research provided a reference for the industrial production of Cy3glc-C12 and extended its application to natural products in lipophilic systems.
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http://dx.doi.org/10.3390/biology9080205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465376PMC
August 2020

Magnetic multiwalled carbon nanotubes with controlled release of epirubicin: an intravesical instillation system for bladder cancer.

Int J Nanomedicine 2019 15;14:1241-1254. Epub 2019 Feb 15.

Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China,

Background: Traditional intravesical instillation treatment in bladder cancer has limited efficacy, which results in a high frequency of recurrence.

Purpose: The aim of this study was to report on an epirubicin (EPI)-loaded magnetic multi-walled carbon nanotube (mMWCNTs-EPI) system for intravesical instillation in place of the current formulation.

Methods: The mMWCNTs-EPI system was formulated with carboxylated MWCNTs, FeO magnetic nanoparticles, and EPI. Features and antitumor activity of the system were investigated.

Results: Under the effect of external magnets, the mMWCNTs-EPI system showed sustained release and prolonged retention behavior and better antitumor activity than free EPI. The mMWCNTs-EPI system had higher efficiency in enhancing cytotoxicity and inhibiting proliferation in vitro and in vivo than free EPI. Our studies also revealed the atoxic nature of mMWCNTs.

Conclusion: These findings suggested that mMWCNTs are effective intravesical instillation agents with great potential for clinical application.
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http://dx.doi.org/10.2147/IJN.S189688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391142PMC
April 2019

A promising therapeutic option for diabetic bladder dysfunction: Adipose tissue-derived stem cells pretreated by defocused low-energy shock wave.

J Tissue Eng Regen Med 2019 06 9;13(6):986-996. Epub 2019 Apr 9.

Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.

Adipose tissue-derived stem cells (ADSCs) have shown effectiveness in treating diabetic bladder dysfunction (DBD). In the present study, ADSCs pretreated by defocused low-energy shock wave (DLSW) were first used to achieve better therapeutic effect. ADSCs were treated by DLSW prior to each passage. Secretions of vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) were tested. Proliferation ability was examined by staining 5-ethynyl-2-deoxyuridine (EdU) and assessing expressions of proliferating cell nuclear antigen (PCNA) and Ki67. DBD rat model was created and subgrouped via therapeutic options of phosphate-buffered saline, ADSCs, pretreated ADSCs, and ADSCs lysate. Afterward, voiding functions were evaluated, and tissues were examined by histology. Neonatal rats received intraperitoneal injection of EdU. All rats were subgrouped and treated as narrated above. Bladder tissues were stained with EdU, Stro-1, and CD34. Results showed that shocked ADSCs were activated by secreting more VEGF and NGF, by higher EdU-retaining cells ratios, and by higher expressions of PCNA and Ki67 compared with unshocked ADSCs. Shocked ADSCs had the most effective efficacy in treating DBD by secreting the most VEGF and NGF to accelerate regenerations of revascularization and innervation. Migrations of EdU Stro-1 CD34 endogenous stem cells to bladders were enhanced by injecting ADSCs. In conclusion, ADSCs pretreated by DLSW had potent therapeutic effect in treating DBD by secreting VEGF and NGF. Recruitment of endogenous stem cells was considered as an important mechanism in this regenerative process.
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http://dx.doi.org/10.1002/term.2844DOI Listing
June 2019

Endogenous Stem Cells Were Recruited by Defocused Low-Energy Shock Wave in Treating Diabetic Bladder Dysfunction.

Stem Cell Rev Rep 2017 Apr;13(2):287-298

Minimally Invasive Urology Center, Shandong Provincial Hospital affiliated to Shandong University, 324 Jing5 Wei7 Road, Jinan, 250021, China.

Defocused low-energy shock wave (DLSW) has been shown effects on activating mesenchymal stromal cells (MSCs) in vitro. In this study, recruitment of endogenous stem cells was firstly examined as an important pathway during the healing process of diabetic bladder dysfunction (DBD) treated by DLSW in vivo. Neonatal rats received intraperitoneal injection of 5-ethynyl-2-deoxyuridine (EdU) and then DBD rat model was created by injecting streptozotocin. Four weeks later, DLSW treatment was performed. Afterward, their tissues were examined by histology. Meanwhile, adipose tissue-derived stem cells (ADSCs) were treated by DLSW in vitro. Results showed DLSW ameliorated voiding function of diabetic rats by recruiting EdUStro-1CD34 endogenous stem cells to release abundant nerve growth factor (NGF) and vascular endothelial growth factor (VEGF). Some EdU cells overlapped with staining of smooth muscle actin. After DLSW treatment, ADSCs showed higher migration ability, higher expression level of stromal cell-derived factor-1 and secreted more NGF and VEGF. In conclusion, DLSW could ameliorate DBD by recruiting endogenous stem cells. Beneficial effects were mediated by secreting NGF and VEGF, resulting into improved innervation and vascularization in bladder.
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http://dx.doi.org/10.1007/s12015-016-9705-1DOI Listing
April 2017

Defocused low-energy shock wave activates adipose tissue-derived stem cells in vitro via multiple signaling pathways.

Cytotherapy 2016 12 7;18(12):1503-1514. Epub 2016 Oct 7.

Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China; Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California, USA. Electronic address:

Background Aims: We found defocused low-energy shock wave (DLSW) could be applied in regenerative medicine by activating mesenchymal stromal cells. However, the possible signaling pathways that participated in this process remain unknown. In the present study, DLSW was applied in cultured rat adipose tissue-derived stem cells (ADSCs) to explore its effect on ADSCs and the activated signaling pathways.

Methods: After treating with DLSW, the cellular morphology and cytoskeleton of ADSCs were observed. The secretions of ADSCs were detected. The expressions of ADSC surface antigens were analyzed using flow cytometry. The expressions of proliferating cell nuclear antigen and Ki67 were analyzed using western blot. The expression of CXCR2 and the migrations of ADSCs in vitro and in vivo were detected. The phosphorylation of selected signaling pathways with or without inhibitors was also detected.

Results: DLSW did not change the morphology and phenotype of ADSCs, and could promote the secretion, proliferation and migration of ADSCs. The phosphorylation levels were significantly higher in mitogen-activated protein kinases (MAPK) pathway, phosphoinositide 3-kinase (PI-3K)/AKT pathway and nuclear factor-kappa B (NF-κB) signaling pathway but not in Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Furthermore, ADSCs were not activated by DLSW after adding the inhibitors of these pathways simultaneously.

Conclusions: Our results demonstrated for the first time that DLSW could activate ADSCs through MAPK, PI-3K/AKT and NF-κB signaling pathways. Combination of DLSW and agonists targeting these pathways might improve the efficacy of ADSCs in regenerative medicine in the future.
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http://dx.doi.org/10.1016/j.jcyt.2016.08.009DOI Listing
December 2016

Partial nephrectomy vs. radical nephrectomy for renal tumors: A meta-analysis of renal function and cardiovascular outcomes.

Urol Oncol 2016 12 21;34(12):533.e11-533.e19. Epub 2016 Oct 21.

Minimally Invasive Urology Center, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China. Electronic address:

Objectives: The widespread use of partial nephrectomy (PN) has led to the preservation of functional renal parenchyma. However, the benefits of PN on renal function and cardiovascular outcomes remain controversial. Thus, a meta-analysis was performed to reconcile the conflicting results.

Materials And Methods: PubMed, Embase, and the Cochrane Library were searched from inception to August 2015, and databases with all relevant comparative studies were included. The Mantel-Haenszel method with random-effects models was used to determine the pooled hazard ratios (HRs) for each outcome.

Results: In total, 26 studies were pooled for new-onset chronic kidney disease, and 6 studies were pooled for cardiovascular outcomes. According to the pooled estimates, PN correlated with a 73% risk reduction of new-onset chronic kidney disease in all included patients (HR = 0.27, P<0.0001) and a 65% risk reduction in patients with tumors>4cm (HR = 0.35, P<0.0001) compared with radical nephrectomy. There were no significant differences between groups regarding postsurgery cardiovascular events (HR = 0.86, P = 0.238) and cardiovascular death (HR = 0.79, P = 0.196). Despite inherent selection biases, the pooled estimates were robust in sensitivity and subgroup analyses.

Conclusions: Our findings suggest that PN lowers the postoperative risk of new-onset chronic kidney disease. Nevertheless, the protection of renal function by PN did not reduce the risk of cardiovascular outcomes. However, this result remains controversial, and additional large-scale evaluations are warranted.
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http://dx.doi.org/10.1016/j.urolonc.2016.07.007DOI Listing
December 2016

Green-light laser en bloc resection for primary non-muscle-invasive bladder tumor versus transurethral electroresection: A prospective, nonrandomized two-center trial with 36-month follow-up.

Lasers Surg Med 2016 11 25;48(9):859-865. Epub 2016 Jul 25.

Department of Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People's Republic of China.

Objectives: To evaluate the safety and efficacy of LBO laser en bloc resection compared with transurethral electroresection (TURBT) for the treatment of primary non-muscle-invasive bladder tumors.

Methods: From September 2010 to February 2012, a prospective, nonrandomized two-center trial was performed. A total of 158 patients (83 underwent laser resection and 75 TURBT) were included in the present study. The preoperative, intraoperative, and postoperative clinical characteristics were recorded and compared in the two groups.

Results: There were no differences with the preoperative characteristics between the patients in the two groups. The mean operative time was 21.46 ± 10.42 minutes for laser resection and 27.47 ± 15.30 minutes for TURBT (P = 0.004). LBO laser group was also associated with less hemoglobin decrease compared with TURBT group (0.87 ± 0.28 g/ml vs. 1.00 ± 0.33 g/ml, P = 0.009). Obturator nerve reflection was absent during laser resection, whereas was observed in nine patients during TURBT (P = 0.001). Two patients in the TURBT group suffered bladder perforation. Three patients in TURBT group and one patient in LBO laser group experienced urethral stricture. The recurrence-free survival rate did not differ significantly between two groups after 36 months follow-up.

Conclusions: The results of our trial have shown that LBO laser en bloc resection is feasible, safe, and effective alternative for the treatment of primary non-muscle-invasive bladder tumors. Besides, it can provide intact specimen for the pathologic diagnosis. Lasers Surg. Med. 48:859-865, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/lsm.22565DOI Listing
November 2016

Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells.

Oncol Lett 2016 Sep 18;12(3):1826-1832. Epub 2016 Jul 18.

Department of Minimally Invasive Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.

Previous studies have demonstrated that the chronic administration of valproic acid (VPA) suppresses angiogenesis ; however, the mechanisms implicated in VPA-induced autophagy remain unclear. The current study aimed to assess VPA-induced autophagy in three prostate cancer cell lines (PC3, DU145 and LNCaP), in addition to analyzing the Akt/mammalian target of rapamycin (mTOR) signal pathway. Prostate cancer cell lines were cultured with various doses of VPA. Cell cycle was analyzed using flow cytometry, and autophagy markers [1A/1B-light chain 3 (LC3)-II and Beclin-1] were examined using transmission electron microscopy, fluorescent microscopy and western blotting. Activation of the Akt/mTOR signal pathway was also assessed by western blotting. The results demonstrated that VPA induced autophagosomes and suppressed the Akt/mTOR signal pathway. This was confirmed by detection of increased LC3-II and Beclin-1 in VPA-treated cells compared with untreated controls. Phosphorylated forms of Akt (PC3, P=0.048; DU145, P=0.045; LNCaP, P=0.039) and mTOR (PC3, P=0.012; DU145, P=0.41; LNCaP, P=0.35) were significantly reduced following VPA treatment. These results suggest that VPA may function as a histone deacetylase inhibitor, suppressing the growth of prostate cancer cells by modulating autophagy pathways, including inhibition of the Akt/mTOR pathway. Further experiments are required to determine the significance of all involved pathways regarding VPA-induced growth inhibition.
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http://dx.doi.org/10.3892/ol.2016.4880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998110PMC
September 2016

Transurethral 160-W straight beam green laser vaporesection of the prostate: initial experience after 180 procedures.

Springerplus 2016 4;5(1):308. Epub 2016 Jul 4.

Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, 324# Jingwu Road, Jinan, 250021 Shandong Province China.

Although the photoselective vaporization of the prostate has been considered one of the most promising alternatives for treatment of benign prostatic hyperplasia (BPH), published clinical data with the surgical technology of straight beam lithium triborate laser (LBO) is still lacking. To evaluate the technical improvement and initial experience of the 160-W straight beam LBO laser photoselective vaporesection of the prostate (PVRP) for the surgical treatment of BPH. From September 2012 to September 2014, including a 12-month follow-up, a prospective randomized study was performed. 180 patients undergoing PVRP were included in the study. All patients were preoperatively assessed by International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), post-void residual urine (PVR), prostate-specific antigen level, and prostate volume measurement. Perioperative parameters and complications were recorded. Patients were reassessed at 1, 3, 6 and 12 months postoperatively. PVRP resulted in a significant improvement of IPSS, Qmax, and PVR. Mean operative time was 48.3 ± 14.4 min. A significant improvement for PVRP was achieved regarding the catheter indwelling and hospital stay time. No severe perioperative complications were recorded. No requiring blood transfusion in all patients. Capsule perforation was observed in four patients in the group. There were four patients experienced bladder neck contracture and another four patients were diagnosed urethral stricture, all of whom were treated well by dilatation finally without reoperation. 160-W straight beam LBO laser PVRP appears to be a feasible and safe alternative for symptomatic BPH with decreased length of catheter indwelling and hospital stay time postoperatively.
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http://dx.doi.org/10.1186/s40064-016-1776-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930913PMC
July 2016

A comparison of incidences of bladder neck contracture of 80- versus 180-W GreenLight laser photoselective vaporization of benign prostatic hyperplasia.

Lasers Med Sci 2016 Nov 30;31(8):1573-1581. Epub 2016 Jun 30.

Minimally Invasive Urology Center, Shandong Provincial Hospital affiliated to Shandong University, 324 Jing5 Wei7 Road, Jinan, 250021, China.

Bladder neck contracture (BNC) after GreenLight laser photoselective vaporization (PVP) of benign prostatic hyperplasia is a common complication. In the present study, data of patients received 80 or 180 W PVP were collected. Perioperative parameters, including applied energy, irradiation time, catheter removal time, and hospital stay, were recorded. Postoperative parameters, including maximum urinary flow rate, International Prostate Symptom Score, post-void residual volume, and incidences of BNC, were recorded at 3 and 12 months after operations. Bladder neck tissues were taken at 3 months after operations for immunohistochemical staining and western blot analysis to examine the expressions of collagen I, matrix metalloproteinase-3 (MMP-3), and transforming growth factor-β (TGF-β). Sample size of patients was calculated with a power of 80 %. Chi-square test and one-way analysis of variance were performed as statistical methods. Three hundred twenty-six patients who received potassium titanyl phosphate (KTP) laser and 256 who received X-ray photoelectron spectroscopy (XPS) laser entered into the study. Perioperative parameters were comparable, except for shorter irradiation time in 180 W group (P = 0.032). Postoperative parameters were also similar, except for higher incidence of BNC in 80 W group at 3 months after operations (P = 0.022). Immunohistochemical staining and western blot analysis showed higher expressions of collagen I, MMP-3, and TGF-β in 80 W group than in 180 W group. In conclusion, 80 W GreenLight laser showed a comparable efficacy with 180-W laser in PVP but showed a higher incidence of BNC in short term, which might be the result of up-regulated fibrotic factors in bladder neck triggered by lasers.
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http://dx.doi.org/10.1007/s10103-016-2017-5DOI Listing
November 2016

A rare case of urachal mucinous adenocarcinoma detected by 18F-FDG PET/CT.

Clin Nucl Med 2015 Mar;40(3):282-5

From the PET/CT Center, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan City, Shandong Province, China.

A 48-year-old woman presented with abdominal pain, and her initial investigations, which included an abdominal ultrasound and a pelvic MRI examination, revealed a dominant soft tissue mass abutting her left iliac bone, extensive pelvic adenopathy, and multiple osseous metastases. The findings were concerning for chondrosarcoma; however, biopsy results were consistent with mucinous carcinoma of unknown origin. A staging 18F-FDG PET/CT revealed a mildly FDG-avid soft tissue mass with scattered calcifications extending to the dome of the urinary bladder, highly suggestive of a primary tumor. Cystoscopy with tissue sampling of this mass demonstrated a primary mucinous adenocarcinoma of the urachus.
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http://dx.doi.org/10.1097/RLU.0000000000000674DOI Listing
March 2015

Magnetic resonance imaging‑directed biopsy improves the prediction of prostate cancer aggressiveness compared with a 12‑core transrectal ultrasound‑guided prostate biopsy.

Mol Med Rep 2014 May 28;9(5):1989-97. Epub 2014 Feb 28.

Department of Radiology, Provincial Hospital, Shandong University, Jinan 250021, P.R. China.

The Gleason grading system is a fundamental indicator of the aggressive nature of prostate cancer (PCa). Diffusion-weighted imaging (DWI) and magnetic resonance (MR) spectroscopy (MRS) are methods for the assessment of PCa aggressiveness. The present study was designed to prospectively investigate whether transrectal ultrasound (TRUS)-guided MR imaging (MRI)-directed biopsies (TRUS‑MR‑Dbs) improve the prediction of PCa aggressiveness in comparison with 12-core TRUS-guided biopsies (TRUS‑Gbs). A total of 518 patients underwent pre-biopsy multi-parametric MRI to identify the clinically suspicious PCa regions. TRUS‑MR‑Dbs were performed on patients with suspected PCa by MRI in addition to TRUS‑Gbs. Only patients who underwent radical prostatectomy (RP) were included in the comparative analysis. TRUS‑biopsy was directed to those areas within suspicious regions with a minimum apparent diffusion coefficient obtained by DWI or with a maximum (choline + creatine)/citrate ratio obtained by MRS. The highest Gleason grades (HGGs) and the Gleason scores (GSs) of specimens were identified. The biopsies and RP results were evaluated using a McNemar test or χ2 analyses using Fisher' exact tests. MRI results were positive in 254 (49.0%) of the 518 patients. TRUS‑MR‑Db detected 165/254 (65.0%) cancer cases and TRUS‑Gb detected 190/518 (36.7%) cancer cases. Forty patients underwent RP. The TRUS‑MR‑Dbs method demonstrated a higher concordance rate (CR) with RP (89.6%) than TRUS‑Gbs (72.9%, P=0.008) for the overall HGG. The CRs with RP for TRUS‑MR‑Dbs vs. those for TRUS‑Gbs were 100 vs. 85.7% (P=0.5), 87.5 vs. 68.8% (P=0.031) and 50 vs. 50% (P=1) for HGG3, HGG4 and HGG5, respectively. The HGG CRs with RP for DWI‑directed biopsies (DWI-Dbs) vs. MRS-directed biopsies (MRS-Dbs) were 77.1 vs. 50.0% (P=0.015) for the overall tumors, 80.0 vs. 40.0% (P=0.003) for peripheral zone tumors and 69.2 vs. 76.9% (P=1) for transition zone tumors. A total of 37 (77.1%) and 25 (52.1%; P=0.007) tumors were assigned accurate GS for TRUS‑MR‑Dbs and TRUS‑Gbs, respectively. The results revealed that TRUS‑MR‑Dbs improved the prediction of PCa aggressiveness and that DWI-Dbs had a superior performance when compared with MRS‑Dbs in the peripheral zone.
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http://dx.doi.org/10.3892/mmr.2014.1994DOI Listing
May 2014

Role of SMAD4 in the mechanism of valproic acid's inhibitory effect on prostate cancer cell invasiveness.

Int Urol Nephrol 2014 May 22;46(5):941-6. Epub 2013 Nov 22.

Minimally Invasive Urology Center, Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan, 250001, China.

Purpose: To investigate the influence of the histone deacetylase inhibitor valproic acid (VPA) on SMAD4 expression and invasive ability of prostate cancer cell lines.

Methods: DU145 and PC3 cell lines were treated with 0, 2, and 5 mMol/l of VPA; invasion of DU145 and PC3 cells were then examined by transwell assay. Immunohistochemistry and Western blot were used to examine SMAD4 protein expression in DU145 and PC3 cells.

Results: Compared with controls, VPA significantly suppressed invasiveness in both PC3 and DU145 cells in a dose-dependent way (P < 0.05). VPA also inhibited AKT protein (which was regarded as an effective indicator here), and meanwhile, SMAD4 expression was down-regulated after VPA treatment in a dose-dependent manner in both DU145 (P < 0.05) and PC3 (P < 0.01) cells.

Conclusions: Valproic acid could suppress invasiveness of prostate cancer cell lines PC3 and Du145, possibly through multiple pathways other than the SAMD4 pathway. This implies that VPA treatment combined with other SMAD4 enhancers could form a basis for a novel prostate cancer treatment.
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http://dx.doi.org/10.1007/s11255-013-0609-6DOI Listing
May 2014

Activation of bone marrow-derived mesenchymal stromal cells-a new mechanism of defocused low-energy shock wave in regenerative medicine.

Cytotherapy 2013 Dec;15(12):1449-57

Minimally Invasive Urology Center, Shandong Provincial Hospital, affiliated with Shandong University, Jinan, China.

Background Aims: Defocused low-energy shock wave (DLSW) therapy has shown effectiveness in regenerative medicine. The mechanism of action was mainly focused on the pathophysiological improvement at the wound tissues. In this study, the activation of stem cells treated by DLSW was first examined as an important pathway during the healing process.

Methods: Cultured rat bone marrow-derived mesenchymal stromal cells (BMSC) were treated by DLSW before each passage. The untreated BMSC served as a control. The secretions of vascular endothelial growth factor (VEGF) and CXC ligand 5 (CXCL5) were tested by means of enzyme-linked immunoassay. Flow cytometry was performed to analyze the BMSC (passage 4) surface antigen expressions (CD166, CD44 and CD34). The expressions of proliferating cell nuclear antigen and Ki67 were analyzed by means of Western blot. The healing abilities of conditioned media of shocked and unshocked BMSC were examined by Matrigel-based capillary-like tube formation assay and rat major pelvic ganglia culture test.

Results: The shocked BMSC secreted more VEGF and CXCL5 than did those of unshocked BMSC. The expressions of CD166, CD44 and CD34 showed no significant differences (P > 0.05) between the shocked and unshocked BMSC. The shocked BMSC demonstrated higher expressions of proliferating cell nuclear antigen (P < 0.01) and Ki67 (P < 0.01) than did those of unshocked BMSC. The shocked BMSC conditioned medium showed higher ability to enhance the growth of major pelvic ganglia neurites (P < 0.05) and Matrigel-based endothelial tube-like formation (P < 0.05).

Conclusions: DLSW did not interfere with the expressions of cell surface markers. DLSW enhanced the secretion and proliferation of BMSC and promoted angiogenesis and nerve regeneration in vitro.
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http://dx.doi.org/10.1016/j.jcyt.2013.08.012DOI Listing
December 2013

Mechanism of growth inhibition of prostate cancer xenografts by valproic acid.

J Biomed Biotechnol 2012 2;2012:180363. Epub 2012 Oct 2.

James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Marburg 205A, 600 North Wolfe Street, Baltimore, MD 21287, USA.

Unlabelled: Valproic Acid (VPA), a histone deacetylase inhibitor, has been demonstrated to cause a marked decrease in proliferation of prostate cancer (PCa) cells in vitro and a significant reduction in tumor volume in vivo. The goal of this study is to better understand the VPA-induced growth inhibition in vivo, by studying expression of various markers in PCa xenografts.

Methods: For in vitro experiments, PCa cells were treated with 0, 0.6, and 1.2 mM VPA for 14 days. For in vivo models, experimental animals received 0.4% VPA in drinking water for 35 days. Tissue microarray was generated using cell pellets and excised xenografts.

Results: VPA treatment causes cell cycle arrest in PCa cells in vivo, as determined by increase in p21 and p27 and decrease in cyclin D1 expression. Increased expression of cytokeratin18 was also seen in xenografts. LNCaP xenografts in treated animals had reduced androgen receptor (AR) expression. While decreased proliferation was found in vitro, increase in apoptosis was found to be the reason for decreased tumor growth in vivo. Also, an anti-angiogenic effect was observed after VPA treatment.

Conclusion: VPA inhibits tumor growth by multiple mechanisms including cell cycle arrest, induction of differentiation, and inhibition of growth of tumor vasculature.
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http://dx.doi.org/10.1155/2012/180363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471003PMC
January 2013

Imaging primary prostate cancer with 11C-Choline PET/CT: relation to tumour stage, Gleason score and biomarkers of biologic aggressiveness.

Radiol Oncol 2012 Sep 19;46(3):179-88. Epub 2012 Jun 19.

Department of Minimally Invasive Urology center, Provincial Hospital Affiliated to Shandong University, Jinan, People's Republic of China.

Background: As a significant overlap of 11C-Choline standardized uptake value (SUV) between prostate cancer and benign prostate hyperplasia (BPH) tissue, controversy exists regarding the clinical value of 11C-Choline PET/CT scan in primary prostate cancer. In this study, the SUVmax of the prostate lesions and the pelvic muscles were measured and their ratios (SUVmax-P/M ratio) were calculated. Then we evaluated whether the tracer 11C-Choline uptake, quantified as SUVmax-P/M ratio, correlated with tumour stage, Gleason score, and expression levels of several biomarkers of aggressiveness.

Methods: Twenty-six patients with primary prostate cancer underwent 11C-Choline PET/CT. Tumour specimens from these patients were graded histopathologically, and immunnohistochemistry for Ki-67, CD31, androgen receptor (AR), Her-2/neu, Bcl-2, and PTEN were performed.

Results: Both SUVmax and SUVmax-P/M ratio showed no significant difference between patients with tumour stage II and III, but significantly elevated in patients with tumour stage IV. SUVmax-P/M ratio was also significantly higher in lesions with Gleason score of 4+3 or higher versus less than or equal to 3+4. SUVmax-P/M ratio was found significantly correlated with expression levels of Ki-67 and CD31. In addition, a higher SUVmax-P/M ratio was demonstrated in Her-2/neu positive subgroup than negative subgroup. At the same time, Gleason score and expression levels of these biomarkers showed no significant association with SUVmax.

Conclusions: Using the parameter SUVmax-P/M ratio, 11C-Choline PET/CT may be a valuable non-invasive imaging technology in the diagnosis of primary prostate cancer.
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http://dx.doi.org/10.2478/v10019-012-0034-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472944PMC
September 2012

160-Watt lithium triboride laser vaporization versus transurethral resection of prostate: a prospective nonrandomized two-center trial.

Urology 2012 Mar;79(3):650-4

Department of Minimally Invasive Urology Center, Provincial Hospital Affiliated to Shandong University, Ji'nan, China.

Objective: To evaluate the safety and efficacy of 160-W lithium triboride laser photoselective vaporization of the prostate (PVP) for the surgical treatment of benign prostatic hyperplasia compared with transurethral resection of the prostate (TURP).

Methods: From July 2010 to January 2011, a prospective nonrandomized study was performed. A total of 108 patients (57 underwent PVP and 51 TURP) were included in the present study. All patients were preoperatively assessed by International Prostate Symptom Score, transrectal ultrasonography, uroflowmetry, and postvoid residual urine volume measurement. The perioperative parameters and complications were recorded. The patients were reassessed at 1, 3, and 6 months postoperatively.

Results: The mean operative time was 57.4 ± 17.3 minutes for TURP and 64.3 ± 20.5 minutes for PVP (P = .044). A significant difference in favor of PVP was achieved for the catheter indwelling time and hospital stay time. Bleeding requiring blood transfusion in 8 patients, and transurethral resection syndrome was observed in 3 patients in the TURP group. Capsule perforation was observed in 5 patients in the TURP group. No severe perioperative complications were recorded in the PVP group. Finally, 4 patients in the TURP group and 1 patient in the PVP group experienced urethral stricture (P = .047).

Conclusion: The results of the present study have shown that 160-W lithium triboride laser vaporization is more favorable in terms of perioperative safety and results in a shorter postoperative catheter time and shorter length of hospital stay than with TURP.
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http://dx.doi.org/10.1016/j.urology.2011.11.039DOI Listing
March 2012

Photoselective vaporization combined with bipolar transurethral resection for the treatment of large prostate adenoma in high-risk patients.

Saudi Med J 2010 Dec;31(12):1320-5

Department of Minimally Invasive Urology, Shandong Provincial Hospital, Shandong University, Jinan, People's Republic of China.

Objective: To evaluate the safety and effectiveness of the combined photoselective vaporization of the prostate (PVP) and bipolar transurethral resection of the prostate (TURP) in high-risk symptomatic patients with large prostates.

Methods: Between January 2007 and January 2010, a prospective study was performed in Shandong Provincial Hospital, Shandong University, Jinan, Shandong Province, China. One hundred and one patients presenting with various kinds of systematic diseases, and with an American Society of Anesthesiologists score of 3 or greater underwent PVP plus bipolar TURP for severe lower urinary tract symptoms due to benign prostatic hyperplasia with prostatic volume greater than 80 ml. The International Prostate Symptom Score (IPSS) and quality-of-life questionnaire (IPPS-QoL), maximum flow rates (Qmax), postvoid urine residues (PVR), and MRI prostatic volumes were recorded. Perioperative data, functional outcome, and complications were evaluated. Patients were reassessed at 3, 6, and 12 months.

Results: The mean operation time was 68.5 ± 23.9 minutes. The mean pre- and post- operative prostate volumes were 102.2 ± 33.1 ml and 40.4 ± 15.6 ml. No severe complications were observed. Significant differences in IPSS, Qmax, and PVR values were recorded within the follow-up period.

Conclusion: The results of our study show that PVP plus bipolar TURP have an excellent efficiency and low morbidity in high-risk patients with large prostates.
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December 2010

Does valproic acid induce neuroendocrine differentiation in prostate cancer?

J Biomed Biotechnol 2011 25;2011:607480. Epub 2010 Oct 25.

James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Marburg 205A, 600 North Wolfe Street, Baltimore, MD 21287, USA.

Valproic Acid (VPA) is a histone deacetylase inhibitor that holds promise for cancer therapy. Here, we investigate whether VPA treatment induces neuroendocrine differentiation of Prostate Cancer (PCa). A tissue microarray of VPA-treated and untreated tumor xenografts and cell lines of human PCa (LNCaP, C4-2, DU145, and PC-3) were generated and were analyzed by immunohistochemical analysis (IHC) for NE markers chromogranin A (CgA), synaptophysin, and NCAM (neural cell adhesion molecule). Western blot analysis for CgA was performed to confirm the results of the TMA. IHC analysis did not reveal any induction of CgA, synaptophysin, or NCAM in any xenograft after VPA treatment in vivo. In vitro, VPA treatment induced little synaptophysin expression in C4-2 and PC-3 cells and NCAM expression in LNCaP and PC-3 cells. In the case of CgA, VPA treatment decreased its expression in vitro in a dose-dependent manner, as determined by western blot analysis. Thus our data demonstrates that VPA does not induce NE differentiation of PCa cells in the physiologically relevant in vivo setting.
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http://dx.doi.org/10.1155/2011/607480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963803PMC
June 2011

C-11 choline PET/CT imaging for differentiating malignant from benign prostate lesions.

Clin Nucl Med 2008 Oct;33(10):671-6

PET/CT Center, Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, China.

Purpose: To investigate the potential of C-11 choline PET/CT imaging for differentiating prostate cancer (PCa) from benign prostate hyperplasia (BPH).

Materials And Methods: Forty-nine patients with prostate lesions underwent C-11 choline PET/CT imaging that was performed 5 minutes after injection of 7.4 MBq/kg (0.2 mCi/kg C-11 choline in the supine position over 2 bed positions (3 minutes per position), covering the pelvis, and the whole body (6 bed) when necessary. After attenuation correction, PET data were analyzed visually and semiquantitatively by measuring maximum standardized uptake value (SUVmax) of the prostate lesions (target) and the muscles (nontarget) and calculating their ratios (P/M).

Results: Twenty-one PCa and 28 BPH lesions were proven histologically. The mean values of the SUVmax of PCa and BPH were 7.87 +/- 5.74 and 4.95 +/- 5.14, respectively without a significant difference between these 2 groups (t = 2.02; P > 0.05). The mean P/M of PCa and BPH were 4.21 +/- 1.61 and 1.87 +/- 0.98. The statistical difference of P/M between them was significant (t = 2.04; P < 0.01). Using 2.3 (P/M) as the criterion, C-11 choline PET/CT imaging showed a sensitivity of 90.48%, a specificity of 85.71%, and a negative predictive value of 92.31%. PET/CT precise localization of the hot spot in different parts of the prostate could contribute to the diagnosis.

Conclusions: C-11 choline PET/CT is a valuable noninvasive imaging technology in the diagnosis of PCa. The parameter P/M could differentiate PCa from benign lesions better than SUV.
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http://dx.doi.org/10.1097/RLU.0b013e318184b3a0DOI Listing
October 2008