Novel model of pyroptosis-related molecular signatures for prognosis prediction of clear cell renal cell carcinoma patients.

Background: Pyroptosis is a programmed death mode of inflammatory cells, which is closely related to tumor progression and tumor immunity. Clear cell renal cell carcinoma (ccRCC) is the major pathological type of renal cell carcinoma (RCC) with poor prognosis. Many theories have tried to clarify the mechanism in the development of ccRCC, but the role of pyroptosis in ccRCC has not been well described. The main purpose of this study is to explore the role of pyroptosis in ccRCC and establish a novel prognosis prediction model of pyroptosis-related molecular signatures for ccRCC. Methods: In the present study, we made a systematical analysis of the association between ccRCC RNA transcriptome sequencing data from The Cancer Genome Atlas (TCGA) database [which included 529 ccRCC patients who were randomized in a training cohort (n=265) and an internal validation cohort (n=264)] and 40 pyroptosis-related genes (PRGs), from which four genes (CASP9, GSDME, IL1B and TIRAP) were selected to construct a molecular prediction model of PRGs for ccRCC. In addition, a cohort of 114 ccRCC patients from Shanghai Eastern Hepatobiliary Surgery Hospital (EHSH) was used as external data to verify the effectiveness of the model by immunohistochemistry. Moreover, the biological functions of the four PRGs were also verified in ccRCC 786-O and 769-P cells by Western blot (WB), CCK-8 cell proliferation, and Transwell invasion assays. Results: The model was able to differentiate high-risk patients from low-risk patients, and this differentiation was consistent with their clinical survival outcomes. In addition, the four PRGs also affected the ability of cell proliferation and invasion in ccRCC. Conclusion: The prediction model of pyroptosis-related molecular markers developed in this study may prove to be a novel understanding for ccRCC.

Cuproptosis-Related lncRNAs Modulate the Prognosis of MIBC by Regulating the Expression Pattern of Immunosuppressive Molecules Within the Tumor Microenvironment.

Background: Cuproptosis-related gene and long non-coding RNA (lncRNA) modulation of cancer regulation is well-established. This investigation aimed to elucidate the prognostic implications of cuproptosis-associated lncRNAs in muscle-invasive bladder cancer (MIBC). Methods: Employing the Cancer Genome Atlas (TCGA) and IMvigor210 cohorts, bioinformatics and statistical analyses probed the prognostic relevance of cuproptosis-related lncRNAs. Results: Co-expression analysis revealed tight associations between lncRNA expression and cuproptosis-linked genes, with 13 cuproptosis-related lncRNAs found to correlate with MIBC prognosis. Lasso regression identified a six-lncRNA prognostic signature, enabling patient stratification into high- and low-risk categories. Tissue validation substantiated differential expression of FAM13A-AS1, GHRLOS, LINC00456, OPA1-AS1, RAP2C-AS1, and UBE2Q1-AS1 between MIBC tumor and normal tissues. Comparative analyses of tumor microenvironments and immune profiles between risk groups disclosed elevated immunosuppressive molecule expression, including programmed cell death-1 (PD-L1) and T-cell immunoglobulin-3 (TIM-3), in high-risk individuals. Conclusion: These findings suggest that cuproptosis-related lncRNAs may modulate the expression of immunosuppressive molecules, thereby influencing MIBC tumorigenesis and progression. Further exploration is warranted to unveil novel therapeutic targets for MIBC based on the expression patterns of cuproptosis-related lncRNAs and their impact on immune responses in the tumor microenvironment.

[Retracted] MicroRNA­616 promotes the growth and metastasis of non­small cell lung cancer by targeting SOX7.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the cell formation assay data shown in Figs. 3D, 4D, 8D and 9D were strikingly similar to data that had already appeared in another article written by different authors at different research institutes [Wang Z, Jiang C, Chen W, Zhang G, Luo D, Cao Y Wu J, Ding Y and Liu B: Baicalein induces apoptosis and autophagy via endoplasmic reticulum stress in hepatocellular carcinoma. Biomed Res Int: 732516, 2014]. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 38: 2078­2086, 2017; DOI: 10.3892/or.2017.5854].

Anlotinib Enhances the Therapeutic Effect of Bladder Cancer with GSDMB Expression: Analyzed from TCGA Bladder Cancer Database & Mouse Bladder Cancer Cell Line.

Introduction and Objective: The mitogen-activated protein kinase (MAPK) pathway is inhibited by the pan-target inhibitor Anlotinib, which induces tumor cell death. In addition to the common apoptosis and necrosis, there is also a pyroptosis mode of cancer cell death in recent years, which is mainly manifested by the cleavage of gasdermin proteins (GSDMs). Gasdermin B (GSDMB) participates in the progression and outcome of bladder cancer. The efficacy and mechanism of Anlotinib in the treatment of GSDMB-positive bladder tumors have not been studied to date. Methods: The relationship between GSDMB expression and tumor stage, overall survival rate, immunotherapy response, tumor recurrence and progression rate was analyzed from the TCGA bladder cancer database. Anlotinib was used to treat GSDMB-positive bladder cancer in mice followed by flow analysis of the secretion of inflammatory factors related to pyroptosis and the level of anti-tumor factors. Western blot analysis detected which MAPK and MEK signal transduction pathways. Results: TCGA data analysis showed that the overall survival rate of bladder cancer patients with high GSDMB expression was better than that of patients with low GSDMB expression. In vivo experiments showed that Anlotinib was more effective in the treatment of GSDMB-positive bladder cancer than GSDMB-negative bladder cancer. Anlotinib can increase the secretion of antitumor-related factors in GSDMB-positive bladder cancer such as TNF-a and CD107a. In addition, Anlotinib also induced an increase in GSDMB protein expression. Anlotinib treatment of GSDMB-positive bladder cancer decreased AKT and MEK protein expression, which were involved in Anlotinib signal transduction pathway. Conclusion: Anlotinib has a strong antitumor effect on GSDMB-positive bladder tumors. This effect is mainly achieved by anlotinib stimulating the secretion of relevant antitumor factors by lymphocytes. The PI3K/AKT and MEK signal transduction pathways were inhibited by Anlotinib in bladder cancer expressing GSDMB protein.

18F-DCFPyL PET/CT in Newly Diagnosed Prostate Cancer: Diagnostic Value of Intraprostatic PSMA Uptake in Risk Classification of Prostate Cancer.

PURPOSE: 18F-DCFPyL prostate-specific membrane antigen (PSMA) PET/CT is commonly applied to locate lesions of prostate cancer (PCa), but its diagnostic function of quantitative parameters is ignored. Our study evaluates the parameters of intraprostatic PSMA uptake in patients newly diagnosed with PCa and explores their predictive value in risk classification, which is similar to D'Amico criteria. MATERIALS AND METHODS: We quantified the maximal standardized uptake value (SUVmax), mean SUV (SUVmean), total lesion (TL)-PSMA, prostate/muscle (P/M) ratio of the primary tumor, and PSMA-derived tumor volume (PSMA-TV) from 62 patients with histologically proven PCa. Patients newly diagnosed with PCa were allocated into risk groups (at low, intermediate, and high risk, respectively) in accordance with D'Amico criteria. Afterwards, the five parameters mentioned above among three different risk groups were compared, and their predictive values in the risk classification of PCa were explored. RESULTS: Significantly decreased levels of SUVmax, SUVmean, TL-PSMA, and P/M ratio were observed in the risk groups of low or intermediate or both, compared with the high-risk group. However, only the P/M ratio significantly elevated in patients with intermediate risk [mean ± SD (median): 46.58 ± 9.74 (45.27), P = 0.042] or high risk [98.95 ± 38.83 (97.52), P < 0.001], compared with low-risk patients [12.33 ± 5.93 (9.81)]. When P/M ratio was used to distinguish between low-risk and intermediate-risk patients, its c-statistics was 0.660. On the other hand, when distinguishing between intermediate-risk and high-risk groups, the c-statistics of P/M ratio was 0.667. Finally, when P/M ratio was used to distinguish between low-risk and high-risk patients, the c-statistics was 0.969. P/M ratio had a positive correlation with prostate-specific antigen in all enrolled PCa patients. CONCLUSION: The quantitative parameters of 18F-DCFPyL PET/CT, including SUVmax, SUVmean, and P/M ratio, might assist in distinguishing low-risk or intermediate-risk groups from the high-risk group. Of these parameters, P/M ratio appears to be the better promising parameter for risk classification of prostate cancer than SUVmax.

ANGPTL3 Overexpression Suppresses the Development of Oncogenic Properties in Renal Cell Carcinoma via the Wnt/ß-Catenin Signaling Pathway and Predicts Good Prognosis.

Angiopoietin-like 3 (ANGPTL3), which is involved in new blood vessel growth, has been reported to exhibit an abnroaml expression in many different cancers. However, the expressing pattern and functions of ANGPTL3 renal cell carcinoma (RCC) were rarely reported. In this study, we observed that ANGPTL3 expression was distinctly downregulated in both RCC specimens from TCGA datasets and cell lines. Survival assays also revealed that patients with low ANGPTL3 expression exhibited a shorter overall survival and disease-free survival than those with high ANGPTL3 expression. Cell counting kit-8 (CCK-8) assay, Colony formation assay, and flow cytometry showed that overexpression of ANGPTL3 distinctly suppressed the proliferation of RCC cells, and promoted apoptosis. Transwell assays and Wound healing assays revealed that ANGPTL3 upregulation suppressed the migration and invasion of RCC cells. Then, we explored whether ANGPTL3 dysregulation influenced the alteration of Wnt/ß-catenin signaling using TOP/FOP flash reporter assays and western blot. The results showed that overexpression of ANGPTL3 distinctly suppressed the activity of Wnt/ß-catenin signaling. Overall, our results confirmed that overexpression of ANGPTL3 was related to the malignancy and good prognosis of RCC patients, and ANGPTL3 upregulation inhibited the tumor proliferation and metastasis via the Wnt/ß-catenin pathway. ANGPTL3 may be a novel therapeutic target and a prognostic biomarker for RCC patients.

Diagnosis of chronic prostatitis by noninvasive methods in elderly patients with benign prostatic hyperplasia in China.

Chronic prostatitis is hard to be identified in BPH patients in clinical works. This study aimed to diagnose chronic prostatitis in BPH patients by noninvasive methods. BPH patients who received transurethral resection of prostate from January 2014 to July 2015 were enrolled in current study. Patients were received examinations of PSA, sex hormones, inflammatory cytokines, metabolic panel and transrectal ultrasonography. According to histological results, patients were divided into two group of BPH with/without prostatitis. Logistic regression was used to find risk factors of chronic prostatitis. As a result, 181 men with an average age of 72.15 ± 8.41 years were enrolled in this study, including 116 patients with prostatitis and 65 patients without prostatitis. The storage sub-score, PSA and IL-2R were significantly higher in patients with prostatitis than those without prostatitis. Based on logistic regression analysis, the above three parameters were also the risk factors of BPH with prostatitis. The diagnostic model was calculated as: 0.317 × storage sub-score + 0.092 × PSA + 0.003 × IL-2R - 4.296. The AUC was 0.725. Histological prostatitis in BPH patients can be diagnosed by the combination of serum IL-2R, PSA and storage sub-score. Identification of chronic prostatitis in BPH patients could more efficiently alleviate urinary symptoms and reduce the risk of disease progression.

Long Non-coding RNA ST8SIA6-AS1 Promotes Lung Adenocarcinoma Progression Through Sponging miR-125a-3p.

Emerging evidence suggests that long non-coding RNA (lncRNA) plays a critical role in human disease progression. Recently, a novel lncRNA ST8SIA6-AS1 was shown as an important driver in various cancer types. Nevertheless, its contribution to lung adenocarcinoma (LUAD) remains undocumented. Herein, we found that ST8SIA6-AS1 was frequently overexpressed in LUAD cell lines, tissues, and plasma. Depletion of ST8SIA6-AS1 significantly inhibited LUAD cell proliferation and invasion in vitro and tumor growth in vivo. In term of mechanism, ST8SIA6-AS1 was transcriptionally repressed by tumor suppressor p53, and ST8SIA6-AS1 was mainly located in the cytoplasm and could abundantly sponge miR-125a-3p to increase nicotinamide N-methyltransferase (NNMT) expression, thereby facilitating LUAD malignant progression. Clinically, high ST8SIA6-AS1 was positively correlated with larger tumor size, lymph node metastasis, and later TNM stage. Moreover, ST8SIA6-AS1 was identified as an excellent indicator for MM diagnosis and prognosis. Collectively, our data demonstrate that ST8SIA6-AS1 is a carcinogenic lncRNA in LUAD, and targeting the axis of ST8SIA6-AS1/miR-125a-3p/NNMT may be a promising treatment for LUAD patients.

Urinary kidney injury molecule-1: a novel biomarker to monitor renal function in patients with unilateral ureteral obstruction.

PURPOSE: This study aimed to investigate the clinical significance of urinary kidney injury molecule-1 (KIM-1) to monitor renal function in patients with obstructive unilateral ureteral calculi. METHODS: Kidneys of 12 male C57BL/6J mice, as well as their urine and plasma specimens, were extracted to detect KIM-1 expressions 24 h after unilateral ureteral obstruction (UUO) construction or sham surgery. Meanwhile, a cohort of 89 patients with unilateral ureteral calculi was retrospectively reviewed. 46 of which received double-J ureteral stent indwelling (group 1) and the remaining 43 were treated conservatively (group 2). Urinary KIM-1 levels in the baseline, 2 h and 1 day after treatments were analyzed. RESULTS: KIM-1 expressions were dramatically higher in mice underwent UUO surgery when compared with the sham group. Clinical data showed urinary KIM-1 levels decreased as time went by for patients in group 1 (1.787 ± 1.081 ng/mL for baseline, 1.668 ± 1.162 ng/mL for 2 h and 0.935 ± 0.526 ng/mL for 1 day after operation; p = 0.0001). Nevertheless, for those in group 2, a mild increase (1.659 ± 0.997 ng/mL, 1.691 ± 0.872 ng/mL and 1.675 ± 0.911 ng/mL, correspondingly; p = 0.9869) was observed. Additionally, a urinary KIM-1 value of 1.04 ng/mL had a sensitivity of 83.1% and specificity of 62.5% to predict the presence of hydronephrosis (95% CI: 0.641-0.873, AUC: 0.757, p < 0.001). CONCLUSIONS: Urinary KIM-1 is a sensitive biomarker of post-renal acute kidney injury (AKI) and might predict the presence of hydronephrosis. It can be used as an effective surrogate to monitor renal function.

ARID1A upregulation predicts better survival in patients with urothelial bladder carcinoma.

OBJECTIVE: AT-rich interactive domain-containing protein 1A (ARID1A) is frequently mutated or deficient in various types of tumors. However, the role of ARID1A in bladder cancer remains unclear. We aimed to evaluate ARID1A expression and its biological role and correlation with prognosis in patients with urothelial bladder carcinoma (BUC). METHODS: ARID1A expression levels in BUC and normal tissues were assessed by immunohistochemistry and correlated with clinicopathological characteristics and patient outcomes. Downregulation of ARID1A was mimicked by transfection with small interfering RNA in T24 bladder cancer cells, and the effects on cell proliferation and migration were evaluated. RESULTS: ARID1A expression was significantly reduced in BUC tissues and was significantly associated with T stage and AJCC stage. Upregulation of ARID1A predicted a better prognosis in BUC patients. ARID1A expression and lymph node status were identified as independent prognostic factors for overall survival. Silencing of ARID1A promoted the proliferation of BUC cells. CONCLUSIONS: ARID1A may represent a novel diagnostic and prognostic biomarker in patients with BUC.

Optimized Anti-Prostate-Specific Membrane Antigen Single-Chain Variable Fragment-Loaded Nanobubbles as a Novel Targeted Ultrasound Contrast Agent for the Diagnosis of Prostate Cancer.

OBJECTIVES: To prepare optimized prostate-specific membrane antigen (PSMA) single-chain variable fragment (scFv)-loaded nanobubbles (NBs) as a novel targeted ultrasound (US) contrast agent for diagnosis and treatment of prostate cancer (PCa). METHODS: Prostate-specific membrane antigen scFv-loaded NBs were prepared by membrane hydration and biotin-streptavidin conjugation. Flow cytometry was used to observe the binding rate of the targeted NBs to PSMA-expressing cells. Contrast-enhanced US was used to monitor targeted and nontargeted NBs administered to nude mice with 22RV1, LNCaP, and PC-3 xenograft tumors. The specific binding ability of the targeted NBs was further examined by fluorescence imaging of tumor cryosections. RESULTS: Uniformly sized targeted NBs were successfully prepared (mean ± SD, 485.3 ± 28.4 nm). The NBs showed good stability and bound specifically to LNCaP and 22RV1 cells with high PSMA expression in vitro but did not bind to PC-3 cells without PSMA expression. The targeted NBs presented good US enhancement, and the results of the in vivo xenograft tumor nude mouse model showed that the peak contrast intensity in LNCaP and 22RV1 cells was significantly higher for the targeted NBs than the nontargeted NBs (P < .05), whereas there was no significant difference in PC-3 cells. Immunofluorescence results obtained from tumor sections confirmed that the targeted NBs were capable of targeting PSMA-expressing tumor cells. CONCLUSIONS: These novel PSMA scFv-loaded NBs have proven to be an excellent US contrast agent for imaging PSMA-expressing PCa and have the potential to not only enable efficient and safe molecular imaging but also to serve as a delivery system for targeted PCa therapies.

LGALS4 as a Prognostic Factor in Urothelial Carcinoma of Bladder Affects Cell Functions.

BACKGROUND: To identify the hub genes related to urothelial carcinoma of the bladder prognosis and to understand their underlying mechanism. METHODS: The expression profiles of 18 pairs of urothelial carcinoma of the bladder patient tissue and paired adjacent tissue obtained from the Cancer Genome Atlas were performed. Weighted gene coexpression network analysis was employed to screen gene modules and hub genes with significant differential expressions in urothelial carcinoma of the bladder. The hub genes expression in urothelial carcinoma of the bladder tissues was validated by reverse transcription-quantitative polymerase chain reaction. The overall survival curve and disease-free survival curve of prognostic factor (LGALS4) were plotted using the Kaplan-Meier method. Furthermore, LGALS4 messenger RNA and protein expression were also assessed in 2 urothelial carcinoma of the bladder cell lines (T24 and 5637) by quantitative reverse transcription-polymerase chain reaction and Western blot. The functions of urothelial carcinoma of the bladder cells with transfected pcDNA3.1-LGALS4 were identified through MTT assay, plate clone formation assay, flow cytometry, and cell migration experiments. RESULTS: LGALS4 was the hub gene of pink module and it was related to prognosis. Higher LGALS4 expression predicted higher probabilities of overall survival and disease-free survival. Overexpression of LGALS4 in urothelial carcinoma of the bladder cells suppressed cell viability and migration but induced apoptosis. CONCLUSION: LGALS4 played a critical role in the progression of urothelial carcinoma of the bladder and held a promise to be the biomarker for diagnosis and treatment of urothelial carcinoma of the bladder. It predicted good prognosis of urothelial carcinoma of the bladder and restrained the growth and migration of urothelial carcinoma of the bladder cells.

Qinwen Baidu decoction for sepsis: A protocol for a systematic review and meta-analysis.

BACKGROUND: Sepsis is the most common critical illness in the clinic, with a high incidence and mortality. Qingwen Baidu decoction (QWBDD) has been widely applied in the treatment of sepsis, however, there is no systematic review or meta-analysis of QWBDD in the treatment of sepsis. Hence, we provide a protocol of systematic review and meta-analysis to evaluate the efficacy and safety of QWBDD in the treatment of sepsis. METHODS: The databases including Cochrane Library, PubMed, Embase, Web of Science, Cochrane Clinical Trial Database, World Health Organization International Clinical Trial Registration Platform, CNKI, CBM, VIP, and WanFang Database will be searched from the time when the respective databases were established to January 2019. All randomized controlled trials (RTCs) published in Chinese and English assessing QWBDD for sepsis will be included. Continuity data are expressed as mean difference (MD) or standard mean difference (SMD), and dichotomous data is expressed as relative risk. Analyses will be performed by using RevMan V.5.3.5 software. RESULTS: This study will provide high-quality synthesis of current evidence of QWBDD in the treatment of sepsis from the following aspects, including 28-day mortality, mean arterial pressure (MAP), blood lactate, procalcitonin (PCT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP), acute physiology and chronic health score (APACHE-II), intensive care unit stay, mean hospital stay, mechanical ventilation time, etc. CONCLUSION:: Our systematic review will provide evidence for judging whether QWBDD is an effective intervention for sepsis. PROSPERO REGISTRATION NUMBER: PROSPERO CRD 42019123078.

Herbal medicine (Zhengan Xifeng Decoction) for essential hypertension protocol for a systematic review and meta-analysis.

BACKGROUND: Essential hypertension is one of the most common chronic diseases worldwide, as well as a leading risk factor for cardiocerebrovascular diseases. Zhengan Xifeng Decoction (ZGXFD) has been widely used to treat essential hypertension, but there is no systematic review by assessing efficacy and safety of ZGXFD on essential hypertension. Therefore, we aim to perform systematic review and meta-analysis to evaluate the efficacy and safety of ZGXFD in the treatment of essential hypertension. METHODS: This systematic review and meta-analysis will be performed by means of electronic databases, including EMBASE, Cochrane Center Registration Controlled trials (Cochrane Library), Web of Science (WOS), World Health Organization International Clinical Trials Registry Platform, PubMed, China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and Wan-fang database. The electronic databases will be searched from their inception to October 2018. This systemic review will include only published English and Chinese articles randomized controlled trials (RTCs) of ZGXFD on essential hypertension. The primary outcome is Efficacy and blood pressure (BP), blood lipid and adverse reactions will be accepted as secondary outcomes. All statistical analyses will be conducted using RevMan V.5.3.5 software. RESULTS: This systematic review and meta-analysis will provide high-quality evidence from several aspects, including for efficacy, blood pressure, blood lipid and adverse effects to evaluate the efficacy and safety of ZGXFD on EHTN. CONCLUSION: This systematic review will determine whether or not ZGXFD is an effective intervention for essential hypertension.

MicroRNA-101 protects bladder of BOO from hypoxia-induced fibrosis by attenuating TGF-ß-smad2/3 signaling.

Bladder outlet obstruction is a common disease, which always evokes urinary bladder wall remodeling significantly. It has been suggested that bladder outlet obstruction can make the bladder progression from inflammation to fibrosis, and hypoxia may play a vital role. It has been found the expression of microRNA-101 varied in bladder after BOO. But what role microRNA-101 and hypoxia play in bladder is not well known. This study is to investigate the mechanism of microRNA-101 and hypoxia in fibrosis of bladder after BOO. We found the expression of microRNA-101 and hif-1α increased in bladder after BOO. Hypoxia could promote the expression of extracellular matrix subtypes and microRNA-101 in BSMCs. When microRNA-101b was translated into BSMCs, the smad2/3 signaling pathway was found to repress. Dual luciferase reporter detected that microRNA-101b attenuated the TGF-ß signaling pathway by inhibiting the expression of TGFßR1. Then, we conclude microRNA-101b is induced by hypoxia and represses fibrosis of BSMCs by inhibiting the expression of TGFßR1 through TGF-ß signaling pathway, and it may be an anti-fibrotic miRNA for therapy. © 2018 IUBMB Life, 71(1):235-243, 2019.

MicroRNA-616 promotes the growth and metastasis of non-small cell lung cancer by targeting SOX7.

MicroRNAs (miRNAs) are a group of important regulators in human types of cancer including non-small cell lung cancer (NSCLC). miR-616 has been found to be a novel cancer-related miRNA. However, the expression and biological function of miR-616 in NSCLC have not been investigated. In this study, qRT-PCR was performed to evaluate the level of miR-616 in NSCLC tissues. MTT, BrdU and Transwell assay were used to investigate the proliferation and metastasis ability of NSCLC cells. Subcutaneous injection model and tail vein injection model were used to evaluate the effect of miR-616 on the in vivo growth and metastasis of NSCLC cells. It was also found that the expression level of miR-616 was increased in NSCLC tissues and cell lines. Patients with a high level of miR-616 had a significantly shorter overall survival and disease-free survival. Functionally, miR-616 overexpression promoted while miR-616 knockdown inhibited the proliferation, migration and invasion of NSCLC cells. Moreover, miR-616 overexpression enhanced the subcutaneous growth and lung metastasis of NSCLC cells in nude mice. Mechanistically, SOX7 was confirmed to be the downstream target of miR-616 in NSCLC cells. Forced expression of SOX7 prevented the promoting effects of miR-616 overexpression on the proliferation and metastasis of NSCLC cells, while knockdown of SOX7 reversed the inhibitory effects of miR-616 knockdown on the proliferation and metastasis of NSCLC cells. In conclusion, the present study indicates that miR-616 is a promising biomarker and therapeutic target in NSCLC.

Long non­coding RNA­GAS5 acts as a tumor suppressor in bladder transitional cell carcinoma via regulation of chemokine (C­C motif) ligand 1 expression.

Long non­coding RNAs (lncRNAs) have important roles in diverse biological processes, including transcriptional regulation, cell growth and tumorigenesis. The present study aimed to investigate whether lncRNA­growth arrest­specific (GAS)5 regulated bladder cancer progression via regulation of chemokine (C­C) ligand (CCL)1 expression. The viability of BLX bladder cancer cells was detected using a Cell Counting kit­8 assay, and cell apoptosis was assessed by annexin V­propidium iodide double­staining. The expression levels of specific genes and proteins were analyzed by reverse transcription­quantitative polymerase chain reaction and western blotting, respectively. In addition, cells were transfected with small interfering (si)RNAs or recombinant GAS5 in order to silence or overexpress GAS5, respectively. The results of the present study demonstrated that knockdown of GAS5 expression promoted bladder cancer cell proliferation, whereas overexpression of GAS5 suppressed cell proliferation. Furthermore, knockdown of GAS5 resulted in an increased percentage of cells in S and G2 phase, and a decreased percentage of cells in G1 phase. In addition, the present study performed a hierarchical cluster analysis of differentially expressed lncRNAs in bladder cancer cells and detected that CCL1 overexpression resulted in an upregulation of GAS5, which may improve the ability of cells to regulate a stress response in vitro. Furthermore, knockdown of GAS5 expression increased the mRNA and protein expression of CCL1 in bladder cancer cells. Gain­of­function and loss­of­function studies demonstrated that GAS5 was able to inhibit bladder cancer cell proliferation, at least in part, by suppressing the expression of CCL1. The results of the present study demonstrated that GAS5 was able to suppress bladder cancer cell proliferation, at least partially, by suppressing the expression of CCL1. The results of the present study may provide a basis for developing novel effective treatment strategies against bladder cancer.

Tailored minimally invasive management of complex calculi in horseshoe kidney.

OBJECTIVE: Complex calculi in horseshoe kidney (HK) present a significant management challenge. Here, we report the clinical efficacy of extracorporeal shock wave lithotripsy (ESWL), minimally invasive percutaneous nephrolithotomy (MPCNL) and flexible ureteroscopy (FURS), combined with holmium laser lithotripsy, in the treatment of calculi in HK. METHODS AND RESULTS: From January 2005 to May 2014, 62 HK patients with renal calculi were reviewed in terms of medical history, treatment modality and therapeutic outcome in a single tertiary care hospital. Among the patients, 11 with a solitary stone ≤ 1.5 cm in diameter received ESWL, leading to overall stone-free rate of 72.7%; 18 with stone diameter ≤ 2-3 cm received retrograde flexible ureteroscopy, with a recorded mean digitized surface area (DSA) of 339.6 ± 103.9 mm2, mean operation time of 93.1 ± 11.5 minutes and overall stone-free rate of 88.9%; and 33 with staghorn or complex calculi (d ≥ 2 cm) had MPCNL or MPCNL-FURS, with a recorded mean DSA of 691.0 ± 329.9 vs. 802.9 ± 333.3 mm2, mean operation time of 106.4 ± 16.6 vs. 124.4 ± 15.1 min and overall stone-free rate of 89.5% vs. 92.9%. For complex calculi (d ≥ 2 cm), MPCNL combined with antegrade FURS was superior in terms of reducing number of tracts, controlling mean hemoglobin drop, but required longer operation time, comparing with MPCNL alone. CONCLUSIONS: As minimally invasive treatments, a combination of MPCNL and antegrade FURS provides a safe and effective modality in the management of staghorn or complex calculi (d ≥ 2 cm) in HK with significantly reduced blood loss comparing to MPCNL alone, and retrograde FURS alone is favorable for stones with a diameter ≤ 2-3 cm. ESWL is effective for viable small solitary stones (d ≤ 1.5 cm). Treatment modality should be tailored based on individual condition.

Comparing the Efficacy of a Multimodular Flexible Ureteroscope With Its Conventional Counterpart in the Management of Renal Stones.

OBJECTIVE: To report our prospective comparison of clinical efficacy between multimodular flexible ureteroscope, PolyScope, and conventional flexible ureteroscope, both combined with holmium laser lithotripsy in managing renal stones <3 cm in diameter. PATIENTS AND METHODS: Between February 2011 and July 2014, a total of 360 adult patients with renal stones were randomized in a single tertiary-care center trial. For 180 patients in each arm, flexible ureteroscopy and holmium laser lithotripsy were done with either PolyScope or Olympus URF P-5 as control. The primary end points were single-session stone fragmentation rate and stone-free rate. The secondary end points comprised operation time, complication rate, and hospital stay. RESULTS: Demographic and preoperative parameters were comparable between 2 groups. For stones of different locations and sizes, single-session stone fragmentation rate of PolyScope was similar to that of URF P-5. However, for lower calyceal stones, URF P-5 was significantly better than PolyScope (82.0% vs 69.2%; P = .022). No statistically significant difference existed in single-session or overall stone-free rate, complication rate, and hospital stay. Mean operation time of PolyScope group was 92.6 ± 20.2 minutes, 9 minutes (10.8%) longer than that of URF P-5 group 83.3 ± 17.1 minutes (P < .01). CONCLUSION: PolyScope demonstrates similar overall stone clearance rate to a conventional flexible ureteroscope in managing renal calculi <3 cm in diameter, but for lower pole stones, it is of inferior efficacy and it is more skillfully demanding, taking longer operation time.

TRPM2 mediates histone deacetylase inhibition-induced apoptosis in bladder cancer cells.

PURPOSE: Inhibition of histone deacetylase (HDAC) activity results in growth arrest and apoptosis in multiple types of cancer cells. It has been well established that p21 is responsible for HDAC inhibitor (HDACi)-induced growth inhibition, while the mechanism underlying HDACi-elicited apoptosis in bladder cancer cells remains largely unknown. METHODS: In this study, the apoptotic response to HDACi (trichostatin A and sodium butyrate) with different concentrations was determined by flow cytometry analysis and real-time polymerase chain reaction was conducted to examine the TRPM2 (Transient receptor potential cation channel, subfamily M, member 2) expression change on HDACi treatment. TRPM2 knockdown and overexpression were performed to investigate the role of TRPM2 in HDACi-induced apoptosis. The mechanism of HDACi-elicited upregulation of TRPM2 was studied by chromatin-immunoprecipitation. RESULTS: HDACi efficiently induced cell apoptosis and TRPM2 upregulation in a time- and dose-dependent manner in T24 bladder cancer cells. Functional analysis revealed that TRPM2 overexpression promotes apoptosis of T24 cells. Conversely, TRPM2 depletion remarkably antagonized HDACi-induced apoptosis. Furthermore, HDAC inhibition-elicited TRPM2 upregulation is caused by the increase of acetylated H3K9 (H3K9Ac) enrichment in TRPM2 promoter. CONCLUSIONS: These data suggest that the HDACi-elicited upregulation of TRPM2 expression is required for HDACi-induced apoptosis in bladder cancer cells and that HDACi activated the enrichment of H3K9Ac-represented permissive chromatin in TRPM2 promoter.