Publications by authors named "Xunbo Jin"

67 Publications

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

Identification and validation of a two-gene metabolic signature for survival prediction in patients with kidney renal clear cell carcinoma.

Aging (Albany NY) 2021 03 3;13(6):8276-8289. Epub 2021 Mar 3.

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

Metabolic reprogramming contributes to the high mortality of advanced stage kidney renal clear cell carcinoma (KIRC), the most common renal cancer subtype. This study aimed to identify a metabolism-related gene (MRG) signature to improve survival prediction in KIRC patients. We downloaded RNA sequencing data and corresponding clinical information for KIRC and control samples from The Cancer Genome Atlas database and identified, based on an MRG dataset in the Molecular Signatures Database, 123 MRGs with differential expression in KIRC. Following Cox regression analysis and least absolute shrinkage and selection operator selection, RRM2 and ALDH6A1 were identified as prognosis-related genes and used to construct a prognostic signature with independent prognostic significance. After risk score-based patient separation, stratified survival analysis indicated that high-risk patients showed poorer overall survival than low-risk patients. We then constructed a clinical nomogram that showed a concordance index of 0.774 and good performance based upon calibration curves. Gene set enrichment analysis revealed several metabolic pathways significantly enriched in the target genes. The two-gene metabolic signature identified herein may represent a highly valuable tool for KIRC prognosis prediction, and might also help identify new metabolism-related biomarkers and therapeutic targets for KIRC.
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http://dx.doi.org/10.18632/aging.202636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034923PMC
March 2021

Comparison of laparoscopic and hand-assisted laparoscopic nephrectomy for inflammatory renal disease: which is the preferred approach?

Ther Adv Urol 2021 Jan-Dec;13:1756287220984046. Epub 2021 Jan 21.

Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 9677, East Jingshi Road, Jinan, 250014, P.R. China.

Aims: Management of inflammatory renal disease (IRD) can still be technically challenging for laparoscopic procedures. The aim of the present study was to compare the safety and feasibility of laparoscopic and hand-assisted laparoscopic nephrectomy in patients with IRD.

Patients And Methods: We retrospectively analyzed the data of 107 patients who underwent laparoscopic nephrectomy (LN) and hand-assisted laparoscopic nephrectomy (HALN) for IRD from January 2008 to March 2020, including pyonephrosis, renal tuberculosis, hydronephrosis, and xanthogranulomatous pyelonephritis. Patient demographics, operative outcomes, and postoperative recovery and complications were compared between the LN and HALN groups. Multivariable logistic regression analysis was conducted to identify the independent predictors of adverse outcomes.

Results: Fifty-five subjects in the LN group and 52 subjects in the HALN group were enrolled in this study. In the LN group, laparoscopic nephrectomy was successfully performed in 50 patients (90.9%), while four (7.3%) patients were converted to HALN and one (1.8%) case was converted to open procedure. In HALN group, operations were completed in 51 (98.1%) patients and conversion to open surgery was necessary in one patient (1.9%). The LN group had a shorter median incision length (5 cm 7 cm,  < 0.01) but a longer median operative duration (140 min 105 min,  < 0.01) than the HALN group. There was no significant difference in blood loss, intraoperative complication rate, postoperative complication rate, recovery of bowel function, and hospital stay between the two groups. Multivariable logistic regression revealed that severe perinephric adhesions was an independent predictor of adverse outcomes.

Conclusion: Both LN and HALN appear to be safe and feasible for IRD. As a still minimally invasive approach, HALN provided an alternative to IRD or when conversion was needed in LN.
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http://dx.doi.org/10.1177/1756287220984046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841654PMC
January 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

The predictive and diagnostic ability of IL-6 for postoperative urosepsis in patients undergoing percutaneous nephrolithotomy.

Urolithiasis 2021 Jan 13. Epub 2021 Jan 13.

Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, No. 324 Jingwu Road, Huaiyin District, Jinan, 250021, Shandong, China.

The aim of this study is to investigate the predictive and diagnostic ability of interleukin-6 (IL-6) for postoperative urosepsis in patients undergoing percutaneous nephrolithotomy (PCNL). 90 patients undergoing PCNL between April 2019 and September 2019 were studied. 16 patients progressed to urosepsis (EXP1 group, n = 16) and 74 patients did not (CON group, n = 74); demographic and perioperative data were compared between these two groups. 25 patients who progressed to postoperative urosepsis without receiving the test of IL-6 between March 2018 and March 2019 were enrolled (EXP2 group, n = 25); demographic and perioperative data were compared between EXP1 group and EXP2 group. Compared with CON group, EXP1 group showed higher serum levels of IL-6 (p < 0.001) and neutrophil (p < 0.001) at postoperative hour two; higher serum levels of IL-6 (p < 0.001), procalcitonin (PCT) (p < 0.05), white blood cell (WBC) (p < 0.05), and neutrophil (p < 0.001) on postoperative day one; higher serum levels of PCT (p < 0.05) and WBC (p < 0.05) on postoperative day three. ROC curves showed IL-6 (AUC = 1.000) at postoperative hour two and PCT (AUC = 0.954) on postoperative day three. Compared with EXP2 group, EXP1 group showed shorter time to intervene (p < 0.001), a shorter postoperative hospital stay (p < 0.001), and a lower incidence rate of severe urosepsis (p < 0.05). There were different diagnostic abilities of IL-6, PCT, WBC, and neutrophil for postoperative urosepsis at different time points, and IL-6 was greatly valuable as a predictive and early diagnosing biomarker for postoperative urosepsis in patients undergoing PCNL at postoperative hour two and on postoperative day one.
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http://dx.doi.org/10.1007/s00240-020-01237-zDOI Listing
January 2021

The retrospective study of perioperative application of dexamethasone and furosemide for postoperative anti-inflammation in patients undergoing percutaneous nephrolithotomy.

Int Urol Nephrol 2021 Apr 7;53(4):669-677. Epub 2021 Jan 7.

Department of Urology, Cheeloo College of Medicine, Shandong Provincial Hospital, Shandong University, No. 324 Jingwu Road, Huaiyin District, Jinan, 250021, Shandong, China.

Objectives: To investigate whether the perioperatively combined application of dexamethasone and furosemide could alleviate the inflammation in patients undergoing percutaneous nephrolithotomy (PCNL).

Patients And Methods: 147 patients undergoing PCNL between November 2018 and October 2019 were enrolled in the study. 77 patients accepted a single dose of dexamethasone and furosemide administration (EXP group, n = 77), and 70 patients did not (CON group, n = 70). Demographic and perioperative data, inflammatory markers including interleukin-6 (IL-6) and procalcitonin (PCT), and clinical outcomes were compared between the two groups.

Results: Compared with the CON group, the incidence rate of urosepsis of the EXP group were significantly lower (11.69% vs. 24.29%, p = 0.046). 3 patients developed severe urosepsis in the EXP group, while 5 patients developed severe urosepsis in the CON group. Compared with those in the CON group, the patients with postoperative urosepsis in the EXP group showed lower serum levels of IL-6 at postoperative hour two (p = 0.045) and at postoperative day one (p = 0.031) and lower serum levels of PCT at postoperative day one (p = 0.015). There was a better clinical outcome of a shorter postoperative hospital stay (p = 0.015) in patients with postoperative urosepsis in the EXP group than in those in the CON group.

Conclusion: The perioperatively combined application of dexamethasone and furosemide was beneficial for alleviating postoperative inflammatory reaction and caused a better clinical outcome of a shorter postoperative hospital stay.
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http://dx.doi.org/10.1007/s11255-020-02718-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032635PMC
April 2021

Corrigendum to "The SLC Family Are Candidate Diagnostic and Prognostic Biomarkers in Clear Cell Renal Cell Carcinoma".

Biomed Res Int 2020 10;2020:1025178. Epub 2020 Dec 10.

Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, 324 Jingwuweiqi Road, Jinan, Shandong 250000, China.

[This corrects the article DOI: 10.1155/2020/1932948.].
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http://dx.doi.org/10.1155/2020/1025178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749763PMC
December 2020

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

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

Safety and oncological outcomes for large (stage ≥T2b) and locally advanced renal cell carcinoma: comparison between laparoscopic and modified hand-assisted laparoscopic radical nephrectomy.

J Int Med Res 2020 Oct;48(10):300060520961238

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

Objective: To compare the operative and oncologic outcomes between hand-assisted laparoscopic radical nephrectomy (HALRN) and laparoscopic radical nephrectomy (LRN) for large (stage ≥T2b) and locally advanced renal cell carcinoma.

Methods: We retrospectively collected data from patients who underwent HALRN or LRN for stage ≥T2b renal cell carcinoma from January 2011 to January 2018 in our institution. The patients' demographics, perioperative parameters, and postoperative follow-up data were compared between the two groups. The survival outcome was estimated using the Kaplan-Meier method.

Results: The HALRN group comprised 78 patients, and the LRN group comprised 63 patients. The median operative duration was significantly shorter in the HALRN than LRN group. The two groups were equivalent in terms of the incision length, blood loss, complication rate, and duration of hospitalization. In the HALRN and LRN groups, the 5-year overall survival rates were 69.4% and 73.1%, the 5-year cancer-specific survival rates were 80.0% and 83.3%, and the 5-year progression-free survival rates were 66.4% and 74.7%, respectively, with no significant differences.

Conclusions: Compared with LRN, HALRN may offer a shorter operative duration and equivalent surgical outcomes without sacrificing oncological efficacy. In addition, HALRN has specific advantages for extremely large and complicated renal tumors.
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http://dx.doi.org/10.1177/0300060520961238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556169PMC
October 2020

Use of Baidu Index to Track Chinese Online Behavior and Interest in Kidney Stones.

Risk Manag Healthc Policy 2020 3;13:705-712. Epub 2020 Jul 3.

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

Background And Aim: Baidu, currently the top online search tool in China, has developed an internet search trends gathering and analysis tool called the Baidu Index. The aim of this study was to explore the value of the Baidu Index for monitoring online kidney stones-related information-seeking behavior and understanding of population features and priorities in China.

Materials And Methods: The Baidu Index was queried using the term "kidney stones" for the period 2014-2018. The search volume was recorded as well as a demand graph, with a geographic and demographic distribution. For surgical treatment modalities, the medical term "extracorporeal shock wave lithotripsy (ESWL)" was analyzed and then compared to the term "kidney stone surgery" to assess changes.

Results: The search trend for the term "kidney stones" remained sustained growth over time. Searches were mostly presented by the age 20-49, in males in the south of China. The demand graph indicated that the diagnosis, followed by the treatment, and dietary control of kidney stones had received the most attention. The search volume related to ESWL showed a similar increasing trend, but was searched with a greater volume than the term "kidney stone surgery" for most of the last 5 years.

Conclusion: The Baidu Index is a useful tool to track online health information-seeking behavior of internet users in China. The geographic and demographic characteristics in kidney stones seem to be reflected in online search trend data to some extent.
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http://dx.doi.org/10.2147/RMHP.S245822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340362PMC
July 2020

The SLC Family Are Candidate Diagnostic and Prognostic Biomarkers in Clear Cell Renal Cell Carcinoma.

Biomed Res Int 2020 1;2020:1932948. Epub 2020 May 1.

Department of Urology, Shandong Province Hospital Affiliated to Shandong University, 324 Jingwuweiqi Road, Jinan, Shandong 250000, China.

Clear cell renal cell carcinoma (ccRCC) is the most common lethal subtype of renal cancer, and changes in tumor metabolism play a key role in its development. Solute carriers (SLCs) are important in the transport of small molecules in humans, and defects in SLC transporters can lead to serious diseases. The expression patterns and prognostic values of SLC family transporters in the development of ccRCC are still unclear. The current study analyzed the expression levels of SLC family members and their correlation with prognosis in ccRCC patients with data from Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), cBioPortal, the Human Protein Atlas (HPA), the International Cancer Genome Consortium (ICGC), and the Gene Expression Omnibus (GEO). We found that the mRNA expression levels of SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were significantly lower in ccRCC tissues than in normal tissues and the protein expression levels of SLC22A6, SLC22A7, SLC22A13, and SLC34A1 were also significantly lower. Except for SLC22A7, the expression levels of SLC22A6, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were correlated with the clinical stage of ccRCC patients. The lower the expression levels of SLC22A6, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were, the later the clinical stage of ccRCC patients was. Further experiments revealed that the expression levels of SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were significantly associated with overall survival (OS) and disease-free survival (DFS) in ccRCC patients. High SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 expression predicted improved OS and DFS. Finally, GSE53757 and ICGC were used to revalidate the differential expression and clinical prognostic value. This study suggests that SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 may be potential targets for the clinical diagnosis, prognosis, and treatment of ccRCC patients.
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http://dx.doi.org/10.1155/2020/1932948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212275PMC
March 2021

A Panel of Urinary Long Non-coding RNAs Differentiate Bladder Cancer from Urocystitis.

J Cancer 2020 1;11(4):781-787. Epub 2020 Jan 1.

Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Huaiyin District, Jinan, Shandong, 250021, China.

Liquid biopsy is becoming a promising method for non-invasive cancer detection. In several proof-of-concept studies, long non-coding RNAs (lncRNAs) were found to be potential biomarkers for bladder cancer detection. The objective of this study was to discover a panel of cell-free, urinary lncRNAs as liquid biopsy biomarkers to non-invasively differentiate bladder cancer from chronic urocystitis. To this end, we collected urine samples from both bladder cancer patients and urocystitis patients. These samples were divided into discovery group and validation group. In the discovery group, the expression levels of 16 cell-free urinary lncRNAs were measured by qPCR to discover candidate biomarkers. The diagnostic performance of the candidate lncRNA biomarkers was then evaluated, which led to a panel of lncRNA biomarkers for bladder cancer detection. The performance of this panel of biomarkers was further evaluated in the validation group to see if these lncRNA biomarkers could discriminate the bladder cancer patients from urocystitis patients. We found that all of the 16 lncRNAs evaluated in this study demonstrated significant difference (<0.05) of expression between bladder cancer patients and urocystitis patients. Nine lncRNAs provided decent diagnostic performance with area under the receiver operating characteristic (ROC) curve (AUC) reaching 0.70 or higher. We then selected the top four lncRNAs, namely UCA1-201, HOTAIR, HYMA1 and MALAT1, to form a panel of urinary biomarkers. Using this panel, bladder cancer patients could be discriminated from urocystitis patients, with sensitivity and specificity reaching 95.7% and 94.3%, respectively. Finally, we confirmed the applicability of the four-lncRNA panel in an independent validation study that included 60 bladder cancer patients and 60 urocystitis patients. Our study paves the way for further studies aimed at large-scale clinical tests of developing lncRNA biomarkers in urine for bladder cancer diagnostics.
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http://dx.doi.org/10.7150/jca.37006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959012PMC
January 2020

Crossed-fused renal ectopia with renal calculi: Two case reports and a review of the literature.

Medicine (Baltimore) 2019 Nov;98(48):e18165

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

Rationale: Crossed renal ectopia (CRE) is a rare congenital anomaly that is frequently associated with gastrointestinal, cardiovascular, genital and bone malformations. To the best of our knowledge, only 35 cases of crossed renal ectopia involving calculi and 30 cases of CRE associated with renal carcinoma have been reported to date.

Patient Concerns: Here, we present 2 cases of crossed renal ectopia. A 59-year-old woman with diabetes presented to our hospital with abdominal pain. The second patient was a 24-year-old woman who complained with abdominal pain with a duration of 1 day.

Diagnoses: On the basis of abdominal ultrasonography, we suspected a solitary kidney both in the two patients. Combined with retrograde pyelography and 3D computed tomography, case 1 was diagnosed as an S-shaped right-to-left crossed-fused ectopic kidney with many stones in the left (normal) renal pelvis and case 2 was confirmed to have lump right-to-left crossed-fused renal ectopia with two 3-mm stones in the renal pelvis of the 2 kidneys.

Interventions: Case 1 underwent percutaneous nephrolithotomy while case 2 refused to undergo surgery and underwent conservative treatment for pain relief.

Outcomes: Two patients have been followed up and have no stones recurrence.

Lessons: Crossed fused renal ectopia is easily misdiagnosed as a solitary kidney. CRE is so rare that the recognition of the disease needs to be improved and effective treatment should be taken timely. According to the two cases and literature review, minimally invasive surgery has become increasingly common to treat CRE with stones and carcinoma.
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http://dx.doi.org/10.1097/MD.0000000000018165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890333PMC
November 2019

Abdominal cocoon with bilateral cryptorchidism and seminoma in the right testis: a case report and review of literature.

BMC Surg 2019 Nov 11;19(1):167. Epub 2019 Nov 11.

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

Background: Abdominal cocoon is a rare peritoneal lesion and is difficult to diagnose because of its lack of special clinical manifestations. Until now, there is no case report of abdominal cocoon combined with cryptorchidism and seminoma.

Case Presentation: A case of abdominal cocoon with cryptorchidism and seminoma was diagnosed and treated in our hospital. The patient had no symptoms except occasional abdominal pain. He underwent laparoscopy because of bilateral cryptorchidism and seminoma in the right testis. During the surgery, he was diagnosed with abdominal cocoon due to the thick fibrous tissues which was tightly adhered and encased part of intestine like a cocoon. Enterolysis and bilateral cryptochiectomy were performed after the diagnosis and nutritional and symptomatic support was provided after the surgery. The patient recovered well and was discharged soon. The postoperative pathological examination confirmed the presence of bilateral cryptorchidism and seminoma in the patient's right testis.

Conclusion: There are only a handful of cases where a patient has both abdominal cocoon and cryptorchidism. Since the etiologies of both diseases remain unknown, further research is required to investigate effective diagnosis and treatment for the diseases and explore the potential connection between the two diseases.
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http://dx.doi.org/10.1186/s12893-019-0636-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849259PMC
November 2019

Correction: Upregulation of long non-coding RNA PlncRNA-1 promotes proliferation and induces epithelial-mesenchymal transition in prostate cancer.

Oncotarget 2019 Aug 27;10(50):5253. Epub 2019 Aug 27.

Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.

[This corrects the article DOI: 10.18632/oncotarget.15318.].
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http://dx.doi.org/10.18632/oncotarget.27174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718261PMC
August 2019

miR-148-3p and miR-152-3p synergistically regulate prostate cancer progression via repressing KLF4.

J Cell Biochem 2019 10 19;120(10):17228-17239. Epub 2019 May 19.

Laboratory of Tumor and Molecular Biology, Academy of Military Medical Sciences, Beijing, China.

Background: miR-148-3p and miR-152-3p as the tumor suppressors have been reported in various cancer types. Our study is aimed to discuss the synergistic effect of miR-148-3p and miR-152-3p in prostate cancer (PCa).

Methods: Bioinformatics algorithm and luciferase reporter assays were used to verify whether miR-148-3p and 152-3p could bind with the 3'-untranslated region (3'-UTR) of Kruppel-like factor 4 (KLF4). PCa cell growth in vivo was analyzed using the mouse xenograft tumor model.

Results: miR-148-3p and miR-152-3p were reduced in PCa tumor tissues. Moreover, the protein expression of KLF4 was increased in PCa tissues. The 3'-UTR of KLF4 contained the conserved binding sites with miR-148-3p and miR-152-3p. The mimics or inhibitors of miR-148-3p and/or miR-152-3p could downregulated or upregulated KLF4 expression, respectively. miR-148-3p and miR-152-3p-induced PCa cell growth inhibition were observed both in vivo and in vitro. KLF4 overexpression had the ability to neutralize the antitumor effect of miR-148-3p/152-3p in vivo and in vitro.

Conclusion: miR-148-3p/152-3p family could serve as tumor suppressors in PCa via repressing KLF4.
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http://dx.doi.org/10.1002/jcb.28984DOI Listing
October 2019

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

Application of fluorescence hybridization in the detection of bladder transitional-cell carcinoma: A multi-center clinical study based on Chinese population.

Asian J Urol 2019 Jan 8;6(1):114-121. Epub 2018 Jun 8.

Department of Urology, The First Hospital of Zhejiang Province, Hangzhou, China.

Objective: To evaluate the diagnostic value of fluorescence hybridization (FISH) in bladder cancer.

Methods: We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and conducted FISH tests and cytology examinations from August 2007 to December 2008. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) values were calculated for both the FISH and urine cytology tests.

Results: A cohort of 988 healthy volunteers was enrolled to establish a reference range for the normal population. A total of 4807 patients with hematuria were prospectively, randomly enrolled for the simultaneous analysis of urine cytology, FISH testing, and a final diagnosis as determined by the pathologic findings of a biopsy or a surgically-excised specimen. Overall, the sensitivity of FISH in detecting transitional-cell carcinoma was 82.7%, while that of cytology was 33.4% ( < 0.001). The sensitivity values of FISH for non-muscle invasive and muscle invasive bladder transitional-cell carcinoma were 81.7% and 89.6%, respectively ( = 0.004). The sensitivity values of FISH for low and high grade bladder cancer were 82.6% and 90.1%, respectively ( = 0.002).

Conclusion: FISH is significantly more sensitive than voided urine cytology for detecting bladder cancer in patients evaluated for gross hematuria at all cancer grades and stages. Higher sensitivity using FISH was obtained in high grade and muscle invasive tumors.
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http://dx.doi.org/10.1016/j.ajur.2018.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363605PMC
January 2019

Long noncoding RNA SNHG16 contributes to the development of bladder cancer via regulating miR-98/STAT3/Wnt/β-catenin pathway axis.

J Cell Biochem 2018 11 21;119(11):9408-9418. Epub 2018 Aug 21.

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

This study aimed to investigate the role and the possible mechanism of the long noncoding small nucleolar RNA host gene 16 (SNHG16) in bladder cancer development. The expression of SNHG16 in the tumor tissues and plasma of patients with bladder cancer as well as bladder cancer cell lines was detected. T24 cells were then transfected with sh-SNHG16 to further investigate the effects of suppression of SNHG16 on T24 cell proliferation, apoptosis, migration, and invasion. In addition, the regulatory relationships between SNHG16 and miR-98 as well as the target of miR-98 were explored. Besides, the association between SNHG16 and the Wnt/β-catenin pathway was further elucidated. The SNHG16 expression was upregulated in the tumor tissues and plasma of patients with bladder cancer, as well as bladder cancer cells. Suppression of SNHG16 inhibited T24 cell proliferation, promoted apoptosis, and suppressed migration and invasion in vitro. In addition, SNHG16 negatively regulated miR-98 expression and regulated the malignant behaviors of T24 cells through sponging miR-98. Moreover, signal transducer and activator of transcription 3 (STAT3) was identified as a functional target of miR-98, and miR-98 regulated the malignant behaviors of bladder cancer cells by targeting STAT3. Besides, suppression of SNHG16 inhibited the activation of the Wnt/β-catenin pathway, which was further regulated by miR-98 and STAT3, indicating that the effects of SNHG16/miR-98/STAT3 on T24 cells were achieved through the Wnt/β-catenin pathway. Our findings reveal that long noncoding RNAs SNHG16 is upregulated in bladder cancer and contributes to the development of bladder cancer possibly via regulating the miR-98/STAT3/Wnt/β-catenin pathway axis. The SNHG16/miR-98/STAT3/Wnt/β-catenin pathway axis may provide a new strategy for bladder cancer treatment.
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http://dx.doi.org/10.1002/jcb.27257DOI Listing
November 2018

Myeloid-derived suppressor cell accumulation in renal cell carcinoma is correlated with CCL2, IL-17 and IL-18 expression in blood and tumors.

Adv Clin Exp Med 2018 Jul;27(7):947-953

Shandong Provincial Hospital, Shandong University, Jinan, China.

Background: Myeloid-derived suppressor cells (MDSC) play an important role in tumor-mediated immune evasion. Levels of MDSC in peripheral blood are increased in patients with cancer, correlating with cancer stage and outcome. Studies have confirmed the associations between MDSC and various cytokines in the peripheral blood of murine and human cancer hosts. However, little is known about the association between parenchymal MDSC subsets and cytokines, or the mechanism drawing MDSC into tumor parenchyma.

Objectives: The aim of this study was to analyze the correlation between MDSC subsets and tumor grade as well as stage in renal cell carcinoma (RCC) patients. The expression of chemokine (C-C motif) ligand 2 (CCL2), interleukin 17 (IL-17) and interleukin 18 (IL-18) in the peripheral blood and parenchyma of RCC patients was also detected to explore its correlation with MDSC accumulation.

Material And Methods: Total MDSC, granulocytic MDSC (G-MDSC), monocytic MDSC (M-MDSC), and immature MDSC (I-MDSC) from the blood and parenchyma were isolated and analyzed by flow cytometry. Cytokines were detected by the enzyme-linked immunosorbent assay (ELISA), real-time polymerase chain reaction (PCR) and western blot in blood and tumors.

Results: Parenchymal levels of MDSC had a positive correlation with levels of CCL2, IL-17, and IL-18, suggesting these cytokines may attract MDSC into the parenchyma. Moreover, peripheral total MDSC, G-MDSC and I-MDSC were shown to correlate with tumor grade and stage. Gene and protein expression of CCL2, IL-17, and IL-18 was significantly increased in blood and tumors of RCC patients.

Conclusions: Our study has provided potential new targets for the risk stratification of patients with limited stages of renal carcinoma, in addition to elucidating a possible association between MDSC subsets and cytokine-induced migration into the tumor tissue.
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http://dx.doi.org/10.17219/acem/70065DOI Listing
July 2018

p53β: a new prognostic marker for patients with clear-cell renal cell carcinoma from 5.3 years of median follow-up.

Carcinogenesis 2018 03;39(3):368-374

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

We previously reported six different p53 isoforms in renal cell carcinoma (RCC). In the present study, influences of p53β on recurrence-free survival (RFS) and overall survival (OS) were evaluated. Patients diagnosed with RCC in our center were into this study. mRNA expressions of p53 isoforms (p53α, p53β, p53γ) in tumors were determined by RT-PCR and real-time PCR. Functional yeast-based assay was performed to analyze p53 mutational status. p53β transfected 786-O and CAKi-1 cells were cultured to examine expressions of B-cell lymphoma 2-associated X protein (bax) and caspase-3, and ratios of apoptosis. After surgeries, all patients were followed up at programmed intervals. 266 patients were analyzed in this study. Median follow-up time was 5.3 years. RT-PCR (r = -0.72, P = 0.016) and real-time PCR (r = -0.65, P = 0.033) both showed only p53β expressed higher level in lower tumor stage versus higher stage. p53 wild-type and p53 mutation had comparable RFS (P = 0.361) and OS (P = 0.218), respectively. Kaplan-Meier analysis showed high p53β expression was associated with significantly improved RFS and OS, regardless of p53 mutational status. High p53β expression indicated better RFS [hazard ratio (HR) 2.599, 95% confidence interval (CI) 1.472-4.551, P = 0.038] and OS (HR 2.604, 95% CI 1.453-4.824, P = 0.031). p53β transfected 786-O and CAKi-1 cells expressed significantly higher level of bax and caspase-3, and had higher ratios of apoptosis than untransfected cells. Taken together, higher level of p53β predict better prognosis in patients with RCC through enhancing apoptosis in tumors.
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http://dx.doi.org/10.1093/carcin/bgy001DOI Listing
March 2018

MicroRNA-138 suppresses cell proliferation and invasion of renal cell carcinoma by directly targeting SOX9.

Oncol Lett 2017 Dec 10;14(6):7583-7588. Epub 2017 Oct 10.

Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250012, P.R. China.

An accumulating number of studies have reported that the expression levels of microRNAs (miRNAs/miRs) are dysregulated in a variety of human cancer types, including renal cell carcinoma (RCC). miRNAs play essential functions in tumorigenesis and the progression of tumors by serving as oncogenes or tumor suppressors. Recently, the expression and functions of miR-138 have been studied in a number of human cancer types; however, its role in RCC remains poorly understood. In the present study, the results revealed that miR-138 was significantly downregulated in RCC cell lines and tissues, and that low expression levels of miR-138 were correlated with histological grade, tumor stage and lymph node metastasis. In functional studies, restoration of miR-138 expression inhibited cell proliferation and invasion of ACHN and A498 cells. In addition, SOX9 was validated as a direct target gene of miR-138 in RCC. SOX9 knockdown inhibited cell proliferation and invasion of RCC, with a similar effect to that induced by miR-138, rendering SOX9 a functional target of miR-138 in the disease. These findings indicate that miR-138 may present a novel target for therapeutic strategies in RCC.
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http://dx.doi.org/10.3892/ol.2017.7160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755254PMC
December 2017

MicroRNA-212 Targets Mitogen-Activated Protein Kinase 1 to Inhibit Proliferation and Invasion of Prostate Cancer Cells.

Oncol Res 2018 Aug 10;26(7):1093-1102. Epub 2018 Jan 10.

Department of Oncology, Qilu Hospital of Shandong University, Shandong, P.R. China.

Prostate cancer (PCa) is the second most commonly diagnosed malignancy and the fifth leading cause of cancer-related deaths in males worldwide. MicroRNAs (miRNAs) may serve as important regulators in PCa occurrence and development. Therefore, understanding the expression and functions of PCa-related miRNAs may be beneficial for the identification of novel therapeutic methods for patients with PCa. In this study, miRNA-212 (miR-212) was evidently downregulated in PCa tissues and several PCa cell lines. Functional assays showed that the resumption of miR-212 expression attenuated cell proliferation and invasion and increased the apoptosis of PCa. In addition, mitogen-activated protein kinase 1 (MAPK1), a well-known oncogene, was identified as a novel target of miR-212 in PCa, as confirmed by bioinformatics, luciferase reporter assay, qRT-PCR, and Western blot analysis. Furthermore, MAPK1 expression was upregulated in PCa tissues and inversely correlated with miR-212 expression. Rescue experiments also demonstrated that restored MAPK1 expression reversed the tumor-suppressing effects of miR-212 on PCa cell proliferation, invasion, and apoptosis. In conclusion, miR-212 may exert tumor-suppressing roles in PCa by regulating MAPK1 and could be a novel therapeutic target for treatment of patients with this malignancy.
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http://dx.doi.org/10.3727/096504018X15154112497142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844748PMC
August 2018

Valproic acid inhibits epithelial‑mesenchymal transition in renal cell carcinoma by decreasing SMAD4 expression.

Mol Med Rep 2017 Nov 29;16(5):6190-6199. Epub 2017 Aug 29.

Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250014, P.R. China.

Renal cell carcinoma (RCC) is the most common malignancy in urogenital neoplasms worldwide. According to previous studies, valproic acid (VPA), an anticonvulsant drug, can suppress tumor metastasis and decrease the expression level of Mothers against decapentaplegic homolog 4 (SMAD4) and therefore may inhibit epithelial‑mesenchymal transition (EMT), which is responsible for cancer metastasis. However, the association between VPA, EMT and SMAD4 in RCC metastasis remains obscure. In the present study, it was demonstrated that in the RCC cell lines 786‑O and Caki‑1 treated with VPA, the neural (N)‑cadherin, vimentin and SMAD4 protein and mRNA levels were decreased, accompanied with an increase in expression of epithelial (E)‑cadherin. Silencing SMAD4 expression decreased the expression of EMT markers, including N‑cadherin and simultaneously upregulated E‑cadherin in RCC cell lines. SMAD4 overexpression counteracted the VPA‑mediated EMT‑inhibitory effect (P<0.05). The present study demonstrates that VPA inhibited EMT in RCC cells via altering SMAD4 expression. In addition, immunohistochemical staining demonstrated that transforming growth factor‑β (TGF‑β) and low expression of SMAD4 was associated with a lower Fuhrman grade and low expression of transcription intermediary factor 1‑γ was associated with a higher tumor Fuhrman grade (P<0.05), Therefore, based on the regulatory effect of SMAD4 on EMT‑associated transcription factors, SMAD4 which can form a SMAD3/SMAD4 complex induced by TGF‑β, could be a potential anticancer drug target inhibiting tumor invasion and metastasis in RCC.
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http://dx.doi.org/10.3892/mmr.2017.7394DOI Listing
November 2017

Utility of fluorescence hybridization analysis for detecting upper urinary tract-urothelial carcinoma.

J Cancer Res Ther 2017 ;13(4):647-650

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

Objectives: The objective of this study was to evaluate the clinical utility of fluorescence in situ hybridization (FISH) in the detection of upper urinary tract-urothelial carcinoma (UUT-UC).

Methods: Between November 2011 and November 2015, voided urine specimens from 52 consecutive patients with UUT-UC and 26 controls were collected for both FISH test and cytology. Sensitivity and specificity of FISH test and cytology were determined and compared. The frequency of chromosomal aberrations was also analyzed.

Results: For FISH analysis, the sensitivity was 79.5% and specificity was 96.3%. For cytology, the sensitivity was 27.3% and specificity was 100%. The overall sensitivity for FISH was significantly higher than that of in single value-based urine cytology (79.5% vs. 27.3%, respectively, P < 0.001). The sensitivities of FISH and cytology by grade were 64.3% vs. 28.6% for low-grade urothelial carcinomas (P = 0.128) and 86.7% vs. 26.7% for high-grade urothelial carcinomas (P < 0.001), respectively. Twenty-seven (77.1%) cases were positive due to the gain of two or more chromosomes in five or more urinary cells, among which, 21 (60%) cases showed positivity in all the 4 chromosomes, 7 (20%) cases matched the criterion that 10 or more cells gained a single chromosome, whereas only 1 (2.9%) case was positive because of the homozygous deletion of 9p21 in 12 or more cells.

Conclusions: FISH has superior sensitivity and similar specificity in the detection of UUT-UC, compared with cytology. The present findings indicated that FISH can be applied as a noninvasive diagnostic tool for suspected UUT-UC patients.
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http://dx.doi.org/10.4103/jcrt.JCRT_74_17DOI Listing
May 2018

Morin promotes prostate cancer cells chemosensitivity to paclitaxel through miR-155/GATA3 axis.

Oncotarget 2017 Jul;8(29):47849-47860

Department of Urology, Shandong Provincial Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong, China.

Paclitaxel is a first-line microtubule-stabilizing drug in treating prostate cancer. However, most patients develop resistance and experience relapse. Morin (3,5,7,20,40-pentahydroxyflavone) is an anti-tumor flavonoid in a numerous types of cancer cells including breast, ovarian and lung cancers. We therefore researched the effects of morin as an adjuvant to paclitaxel in in treating DU145 and PC-3 cells in vitro and DU145 derived prostate cancers in nude mice models. The chemosensitivities of these cells to the treatments of morin and paclitaxel were tested through viability assays utilizing cell counting kit 8 (CCK-8) and apoptosis assays through flow cytometry analyses. MicroRNA (miRNA) microarray was employed to determine the changes in miRNA profile of morin treated DU145 cells. The results from microarrays were further certified by quantitative real-time reverse transcription-PCR (qRT-PCR). The underlying targets of miR-155 were verified using luciferase assays followed by Western blot assays. In the results, morin was capable of repressing the cell viabilities in the paclitaxel-treated cells. MiR-155might be an effective target that can be down-regulated in morin-treated cells. We also discovered that GATA binding protein 3 (GATA3) was directly repressed by miR-155, and the treatment of morin reversed the expression of GATA3. In conclusion, morin might be a potential adjuvant of paclitaxel in treating prostate cancer through regulating miR-155/GATA3 axis.
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http://dx.doi.org/10.18632/oncotarget.18133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564610PMC
July 2017

LncRNA CCAT1 inhibits cell apoptosis of renal cell carcinoma through up-regulation of Livin protein.

Mol Cell Biochem 2017 Oct 3;434(1-2):135-142. Epub 2017 May 3.

Department of Minimally Invasive Urology Center, Provincial Hospital Affiliated to Shandong University, 9677# Olympic Sports Centre Middle Road, Jinan, 250014, Shandong, People's Republic of China.

This study was to investigate the involvement of long non-coding RNA (lncRNA) colon cancer-associated transcript-1 (CCAT1) in renal cell carcinoma (RCC) and to further uncover its underlying mechanism. In this study, the expression of CCAT1 and Livin of RCC tissues or cells was determined using qRT-PCR (quantitative real-time PCR) and western blot, respectively. RNA pulldown and RIP (RNA-Binding Protein Immunoprecipitation) assays were performed to examine the sequence interaction between CCAT1 and Livin. The viability and apoptosis of RCC cells was assessed by MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and TUNEL (TdT-mediated dUTP nick end labeling) assays, respectively. Mice of tumor animal models were established to observe the effect of CCAT1 on RCC tumor growth. The relative expression of CCAT1 in RCC tissues and cell lines was obviously higher than that of the control. CCAT1 knockdown could reduce cell viability and increase the apoptosis of RCC cells in vitro. Furthermore, Livin was significantly inhibited by CCAT1 silencing; RNA pulldown and RIP assays showed that CCAT1 was physically associated with Livin protein. Moreover, Livin overexpression not only significantly inhibited RCC cell apoptosis and increased cell viability, but completely reversed the si-CCAT1-mediated repression of cell viability. More importantly, CCAT1 silencing could inhibit the growth of RCC in vivo that was accompanied by the reduction of Livin in RCC tissues. CCAT1 inhibits RCC cell apoptosis and increases cell viability through up-regulation of Livin.
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http://dx.doi.org/10.1007/s11010-017-3043-8DOI Listing
October 2017