Development and first-in-human study of PSMA-targeted PET tracers with improved pharmacokinetic properties.

PURPOSE: A series of new 68Ga-labeled tracers based on [68Ga]Ga-PSMA-617 were developed to augment the tumor-to-kidney ratio and reduce the activity accumulation in bladder, ultimately minimize radiation toxicity to the urinary system. METHODS: We introduced quinoline group, phenylalanine and decanoic acid into different tracers to enhance their lipophilicity, strategically limiting their metabolic pathway through the urinary system. Their binding affinity onto LNCaP cells was determined through in vitro saturation assays and competition binding assays. In vivo metabolic study, PET imaging and biodistribution experiment were performed in LNCaP tumor-bearing B-NSG male mice. The most promising tracer was selected for first-in-human study. RESULTS: Four radiotracers were synthesized with radiochemical purity (RCP) > 95% and molar activity in a range of 20.0-25.5 GBq/µmol. The binding affinities (Ki) of TWS01, TWS02 to PSMA were in the low nanomolar range (< 10 nM), while TWS03 and TWS04 exhibited binding affinities with Ki > 20 nM (59.42 nM for TWS03 and 37.14 nM for TWS04). All radiotracers exhibited high stability in vivo except [68Ga]Ga-TWS03. Micro PET/CT imaging and biodistribution analysis revealed that [68Ga]Ga-TWS02 enabled clear tumor visualization in PET images at 1.5 h post-injection, with higher tumor-to-kidney ratio (T/K, 0.93) and tumor-to-muscle ratio (T/M, 107.62) compared with [68Ga]Ga-PSMA-617 (T/K: 0.39, T/M: 15.01) and [68Ga]Ga-PSMA-11 (T/K: 0.15, T/M: 24.00). In first-in-human study, [68Ga]Ga-TWS02 effectively detected PCa-associated lesions including primary and metastatic lesions, with lower accumulation in urinary system, suggesting that [68Ga]Ga-TWS02 might be applied in the detection of bladder invasion, with minimized radiation toxicity to the urinary system. CONCLUSION: Introduction of quinoline group, phenylalanine and decanoic acid into different tracers can modulate the binding affinity and pharmacokinetics of PSMA in vivo. [68Ga]Ga-TWS02 showed high binding affinity to PSMA, excellent pharmacokinetic properties and clear imaging of PCa-associated lesions, making it a promising radiotracer for the clinical diagnosis of PCa. Moreover, TWS02 with a chelator DOTA could also label 177Lu and 225Ac, which could be used for PCa treatment without significant side effects. TRIAL REGISTRATION: The clinical evaluation of this study was registered On October 30, 2021 at https://www.chictr.org.cn/ (No: ChiCTR2100052545).

[Causes of missed diagnosis of clinically significant prostate cancer by targeted biopsy].

OBJECTIVE: To retrospectively analyze the causes of missed diagnosis of clinically significant PCa (csPCa) by targeted biopsy (TB). METHODS: This retrospective study included 652 males aged (71.32 ± 16.53) years with elevated PSA and abnormal MRI signals detected in our hospital from June 2018 to December 2020. We further examined the patients by transperineal prostatic TB and systematic biopsy (SB), analyzed the detection rates of PCa and csPCa by TB and SB, and investigated the causes of missed diagnosis of csPCa in TB using the fishbone diagram. RESULTS: The total detection rate of PCa and csPCa by TB combined with SB was 45.7% (298/652), and that of csPCa was 37.4% (244/652), with 38 cases of csPCa missed in TB, including 23 cases of negative TB and 15 cases of low ISUP grade. The causes of missed diagnosis of csPCa by TB included low MRI image quality, PSA density ≤0.15 ng/ml/cm3, target area <10 mm, and PI-RADS 2 score ≤3. The detection rate of csPCa by TB alone was 31.6%, which was increased by 5.8% (P = 0.027) when TB combined with SB. CONCLUSION: TB combined with SB yields a higher detection rate of csPCa than either used alone. Missed diagnosis of csPCa by TB is closely related to the characteristics of tumor and MR image of the target area.

Molecular classification of patients with NMIBC predicts the efficacy of intravesical chemotherapy with pirarubicin, pharmorubicin and gemcitabine-immunohistochemistry-based classification.

OBJECTIVE: To investigate the relationships between non-muscle invasive bladder cancer molecular subtypes and predict the efficacy of intravesical chemotherapy with pirarubicin, pharmorubicin and gemcitabine. METHODS: A total of 160 patients with T1 stage non-muscle invasive bladder cancer were enrolled in this study. Fifty-three patients underwent anthracycline (Pirarubicin and Pharmorubicin) therapy and 107 patients accepted gemcitabine therapy. Uroplakin II and CK20 were categorized as immunohistochemistry (IHC) markers for luminal subtype, whereas CK5/6 and CD44 were categorized as immunohistochemistry markers for basal subtype. The cluster results with immunohistochemical score indicated that non-muscle invasive bladder cancer can be subgrouped into three major classes. RESULTS: Class 2 showed the luminal-like characteristics, whereas class 3 showed the basal-like characteristics. Class 1 showed no high expression of luminal or basal-associated immunohistochemistry markers. The molecular subtype is an independent risk factor for recurrence-free survival (P = 0.030) and progression-free survival (P = 0.006) in patients with T1 stage non-muscle invasive bladder cancer. In class 1 and class 2 (luminal-like) subtypes, gemcitabine and anthracycline show no difference in recurrence-free survival and progression-free survival. Gemcitabine was associated with reduced recurrence compared with anthracycline (P = 0.039) in class 3 (basal-like) subtypes and show no difference in decreasing progression. CONCLUSIONS: The molecular classification based on immunohistochemical results is an independent risk factor for the prognosis of non-muscle invasive bladder cancer with T1 stage. Different therapeutic methods should be selected according to different molecular subtypes.

Investigation of Leptin G19A polymorphism with bladder cancer risk: A case-control study.

BACKGROUND: A host of studies show Leptin (LEP) G19A polymorphism is correlated with the risk of various cancers, but the connection of this polymorphism with bladder cancer (BC) risk has not been reported. MATERIALS AND METHODS: This association was in explored in a case-control study involving 355 BC cases and 435 controls (all Chinese Han). Polymerase chain reaction-restriction fragment length polymorphism was conducted to genotype LEP G19A polymorphism. Analyses of allele and genotype distribution were evaluated using chi-square test. Continuous data were assessed by an independent samples t test or one-way ANOVA test. Odds ratio (OR) and 95% confidence interval (CI) were determined by logistic regression. RESULTS: LEP G19A polymorphism was significantly associated with a lower risk of BC (AA vs GG: adjusted OR, 0.40, 95% CI, 0.20-0.83, P = .013; AA + GA vs GG: adjusted OR, 0.70, 95% CI, 0.52-0.93, P = .015; AA vs GA + GG: adjusted OR, 0.45, 95% CI, 0.22-0.91, P = .026). In addition, A allele was associated with decreased risk for BC (A vs G: OR, 0.70, 95% CI, 0.55-0.89, P = .003). Stratified analyses by females, non-drinkers, and non-smokers all returned considerable relations. Furthermore, LEP G19A polymorphism was correlated with tumor size, tumor node metastasis, and distant metastasis in BC patients. CONCLUSIONS: LEP G19A polymorphism is associated with a less risk of BC.

[Inhibin B level helps evaluate the testicular function of prepubertal patients with varicocele].

OBJECTIVE: To investigate the role of the serum inhibin B (INHB) level in evaluating the testicular function of the prepubertal patient with varicocele (VC) after high ligation of the spermatic vein (HLSV). METHODS: This study included 31 prepubertal male patients with left VC, averaging 12.55 years of age and 9 complicated by right VC. We collected peripheral blood samples before and at 4, 12 and 26 weeks after HLSV as well as spermatic venous blood samples intraoperatively for determination of the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), anti-sperm antibody (AsAb) and serum INHB by ELISA. RESULTS: Compared with the baseline, statistically significant differences were observed in the INHB level in the peripheral blood at 12 and 26 weeks after operation (ï¼»255.18 ± 69.97ï¼½ vs ï¼»141.78 ± 59.82ï¼½ pg/ml, P < 0.05) and that in the spermatic venous blood intraoperatively (ï¼»255.18 ± 69.97ï¼½ vs ï¼»412.44 ± 259.42ï¼½ pg/ml, P < 0.01). Spearman's analysis showed a negative correlation between the level of INHB and that of FSH (r = －0.224, P < 0.01). CONCLUSIONS: The level of serum INHB in the peripheral blood of the prepubertal VC patient is decreased within 6 months after HLSV and negatively correlated with that of FSH. The levels of INHB and FSH may well reflect the testicular function of the prepubertal VC patient.

LINC00312 inhibits the migration and invasion of bladder cancer cells by targeting miR-197-3p.

To investigate the influence of the long non-coding RNA LINC00312 on bladder cancer (BC) cell invasion and metastasis by targeting miR-197-3p. BC and corresponding adjacent tissues were collected. LINC00312 and miR-197-3p were measured, and their correlation was detected through quantitative real-time PCR (qRT-PCR). BC cell line T24 was transfected and grouped (five groups) according to different transfection conditions. A scratch test was applied to analyze cell migration, and a Transwell assay was used to test cell invasion ability. Western blotting was to measure matrix metalloproteinase (MMP)-2, MMP-9, and the tissue inhibitor of metalloproteinase 2 (TIMP2) protein levels. qRT-PCR indicated that LINC00312 expression was lower but miR-197-3p expression was higher in BC tissues compared with adjacent tissues; LINC00312 was negatively correlated with miR-197-3p. The migration test revealed that the downregulation of miR-197-3p and overexpression of LINC00312 inhibited cell migration and invasion abilities, while the overexpression of miR-197-3p and the upregulation of LINC00312 promoted cell migration and invasion. BC cells with downregulated miR-197-3p or upregulated LINC00312 had low MMP-2 and MMP-9 levels but high TIMP2. LINC00312 inhibited BC cell invasion and metastasis through mediating miR-197-3p.

Hsa-miR-146a-5p modulates androgen-independent prostate cancer cells apoptosis by targeting ROCK1.

BACKGROUND: MicroRNAs (miRNAs) have been demonstrated playing important roles in the procession of prostate cancer cells transformation from androgen-dependence to androgen-independence. METHODS: We conducted the miRNA microarray and realtime PCR analyses in both androgen-dependent (ADPC) and androgen-independent prostate cancer (AIPC) tissues. We also explored the role of hsa-miR-146a-5p (miR-146a) in MSKCC prostate cancer clinical database. Moreover, the impact of miR-146a on prostate cancer cells apoptosis were detected by Hoechst staining and fluorescence-activated cell sorter (FACS). Its target is predicted by DIANA LAB online database and the result was assumed by western blotting and luciferase assay. RESULTS: We demonstrated that miR-146a was down-regulated in AIPC tissues and cell lines compared to that in the ADPC tissues. In MSKCC data re-analyses, we found that miR-146a was underexpressed in metastatic prostate cancer tissues and those with Gleason score >8, moreover, low level of miR-146a represented a high biochemical relapse rate after radical prostatectomy. In the functional analyses, we transfected miR-146a mimics into CPRC cell lines and found miR-146a induced cells apoptosis. In mechanic analyses, we found that miR-146a inhibited the basal level of Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) expression by targeting its 3'UTR and an inverse correlation of expression between miR-146a and ROCK1 was observed. Moreover, caspase 3 activity was stimulated by miR-146a overexpression. CONCLUSION: miR-146a has a critical role in the process of AIPC prostate cancer cells apoptosis through regulation of ROCK/Caspase 3 pathway. Targeting this pathway may be a promising therapeutic strategy for future personalized anti-cancer treatment.

NADPH oxidase subunit p22(phox)-mediated reactive oxygen species contribute to angiogenesis and tumor growth through AKT and ERK1/2 signaling pathways in prostate cancer.

Excessive generation of reactive oxygen species (ROS) in cancer cells is associated with cancer development, but the underlying mechanisms and therapeutic significance remain elusive. In this study, we reported that levels of ROS and p22(phox) expression are greatly increased in human prostate cancer tissues, and knockdown of p22(phox) by specific small interfering RNA (siRNA) decreased ROS levels in prostate cancer cells. We also showed that stable downregulation of p22(phox) in prostate cancer cells inhibited cell proliferation and colony formation, which was mediated by AKT and extracellular signal-regulated kinase (ERK)1/2 signaling pathways and their downstream molecules hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF). The NADPH oxidase subunit NOX1 was also elevated in prostate cancer cells, and was involved in activation of AKT/ERK/HIF-1/VEGF pathway and regulation of cell proliferation. Knockdown of p22(phox) resulted in inhibition of tumor angiogenesis and tumor growth in nude mice. These findings reveal a new function of p22(phox) in tumor angiogenesis and tumor growth, and suggest that p22(phox) is a potential novel target for prostate cancer treatment.

Solitary Fibrous Tumor of the Prostate Shown on FAPI PET/CT.

ABSTRACT: Solitary fibrous tumors are fibroblast tumors that occur mainly in the peritoneum, extremities, and pleura. Here, we report the MRI, FDG PET/CT, and FAPI PET/CT findings of a rare prostate solitary fibrous tumor. A 57-year-old man was pathologically diagnosed with a solitary fibrous tumor. To detect any systemic metastases or other primary lesions, the patient underwent FDG PET/CT and FAPI PET/CT examination sequentially. Mild FDG uptake was observed in the primary prostatic lesion, but there was a significant uptake of FAPI in the prostate. This case highlighted that FAPI PET/CT may outperform FDG PET/CT in identifying solitary fibrous tumors.

MiR-146a suppresses tumor growth and progression by targeting EGFR pathway and in a p-ERK-dependent manner in castration-resistant prostate cancer.

BACKGROUND: Castration-resistant prostate cancer (CRPC) is a leading cause of cancer-related deaths in elder men. This disease has limited therapeutic options and poor prognosis as the underlying molecular mechanisms are not clearly understood. Given the emerging roles of microRNA (miRNA) as a key regulator, we postulated that miRNA may play a significant role in CRPC formation. METHODS: miR-146a levels in 15 androgen-dependent prostate cancer (ADPC) tissues and 5 CRPC tissues were measured by qRT-PCR. Effects of miR-146a in cell proliferation and migration in vitro and in vivo were evaluated by MTT assay, colony formation assay, transwell migratory assay, and tumor formation assay, respectively. RESULTS: we found that miR-146a expression was significantly decreased in CRPC tissues compared to ADPC tissues. Functional analyses showed that ectopic overexpression of miR-146a in androgen-independent cell lines not only inhibited cell growth, colony formation, and migration in vitro, but also reduced tumorigenicity and angiogenesis in vivo. Mechanistic studies revealed that miR-146a repressed the expression of EGFR through binding to its 3'-untranslated region. Also, miR-146a inhibited the expression of MMP2, one of the most important genes in tumor progression. Moreover, downregulation of p-ERK expression significantly abrogated miR-146a-induced prostate cancer cell proliferation. CONCLUSIONS: Our findings suggest that ubiquitous loss of miR-146a is a critical mechanism for overexpression of EGFR in CRPC, which is crucial to better understanding the pathogenesis of CRPC.

Deep-Learning-Guided Student Intelligent Classroom Management System.

Aiming at the limitations of old-fashioned instructing knowledge and the insufficiency of existing dynamically managed classrooms, a deep-learning-guided Unity3D-based intelligent classroom management system and the corresponding instrument support were proposed. We first build a virtual scene and import Unity3D motors, in order to improve practical fake action proofs through C# script and prefix system. Subsequently, we attempt to solve the permission arrangement proposition in multiperson entity scenes, and accordingly, we complete the cognitive assistance module using authorization strategy. Our system can provide different students with tailored permissions, foresee text, video, and some flexible functions. Our system can be divided into multiple Spring Cloud frameworks. We further leverage the Redis to optimize the system architecture. The system can be conveniently applied in chemistry instructing with clear virtual auditions under the government direct supervision. It can effectively address authority issues in real scenarios while enhancing the learning efficiency and increasing accessibility. A set of intelligent classroom behavior system based on deep learning that supported by cunning learning methods are proposed accordingly. It can complete the classroom perception ministry. It can optimally conduct status monitoring as well as classroom assignment and discussion services through deep learning vision techniques such as face perception and facial expression analysis. Extensive experimental results have shown the competitive performance of our method.

Distributed model-free formation control of networked fully-actuated autonomous surface vehicles.

This paper presents a distributed constant bearing guidance and model-free disturbance rejection control method for formation tracking of autonomous surface vehicles subject to fully unknown kinetic model. First, a distributed constant bearing guidance law is designed at the kinematic level to achieve a consensus task. Then, by using an adaptive extended state observer (AESO) to estimate the total uncertainties and unknown input coefficients, a simplified model-free kinetic controller is designed based on a dynamic surface control (DSC) design. It is proven that the closed-loop system is input-to-state stable The stability of the closed-loop system is established. A salient feature of the proposed method is that a cooperative behavior can be achieved without knowing any priori information. An application to formation control of autonomous surface vehicles is given to show the efficacy of the proposed integrated distributed constant bearing guidance and model-free disturbance rejection control.

[Corrigendum] MicroRNA­335 is downregulated in bladder cancer and inhibits cell growth, migration and invasion via targeting ROCK1.

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that, in Fig. 3 on p. 4382, the 'Invasion' assay data for the negative control (NC) experiments for the T24 and EJ cell lines appeared to contain an overlap of data, such that they may have been derived from the same original source even though the data were purportedly intended to show the results from differently peformed experiments. The authors have re­examined their original data, and realize that this figure was inadvertently assembled incorrectly. The revised version of Fig. 3, showing alternative data from one of the repeated experiments, is shown below. Note that this error did not significantly affect either the results or the conclusions reported in this paper, and all the authors agree to this corrigendum. Furthermore, the authors thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 13: 4379-4385, 2016; DOI: 10.3892/mmr.2016.5055].

[Corrigendum] MicroRNA­379­5p plays a tumor­suppressive role in human bladder cancer growth and metastasis by directly targeting MDM2.

Following the publication of the above article, an interested reader drew to the authors' attention that the cell and invasion migration assay data featured in Figs. 2C and 5D contained two pairs of overlapping panels, such that the data appeared to have been derived from the same original sources, even though the data panels were intending to show the results from differently performed experiments. Moreover, there was also an instance of duplicated data panels comparing between the si­NC/cell invasion and si­NC/cell migration assay panels in Fig. 4C. After having examined their original data, the authors have realized that inadvertent errors were made during the process of compiling these figures. Corrected versions of Figs. 2, 4 and 5, incorporating all the data from one of the repeated experiments, are shown opposite and on the next page. The authors all agree to the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this. They also regret any inconvenience caused to the readership of the Journal. [Oncology Reports 57: 3502­3508, 2017; DOI: 10.3892/or.2017.5607].

miR-143 decreases prostate cancer cells proliferation and migration and enhances their sensitivity to docetaxel through suppression of KRAS.

MicroRNAs have been implicated in regulating diverse cellular pathways. Emerging evidence indicates that miR-143 plays causal roles in cancer tumorigenesis as a tumor suppress gene; however, its role in prostate cancer tumorigenesis remains largely unknown. The aims of this study were to verify the effect of miR-143 on proliferation and migration abilities of prostate cancer cells. The expression level of miR-143 and its target gene KRAS were measured by realtime PCR and western blotting, respectively. Effects of miR-143 in cell proliferation, migration and chemosensitivity were evaluated by MTT assay, FACS cell cycle analysis, colony formation assay, and transwell migratory assay. Our results revealed an inverse correlation of expression between miR-143 and KRAS protein in prostate cancer samples (Pearson's correlation scatter plots: R = -0.707, P < 0.05). Moreover, over-expression of miR-143 in prostate cancer cells suppressed their proliferation and migration and increased their sensitivity to docetaxel by targeting EGFR/RAS/MAPK pathway. These findings suggest that miR-143 plays an important role in prostate cancer proliferation, migration and chemosensitivity by suppressing KRAS and subsequent inactivation of MAPK pathway, which provides a potential development of a new approach for the treatment of prostate cancer.

Characterization of lactoferrin receptor on human spermatozoa.

Lactoferrin (LF) is abundant in human seminal plasma and on sperm surfaces. However, lactoferrin receptor (LFR) on human spermatozoa has not yet been reported. To study the expression, localization and characteristics of LFR on human spermatozoa, different experimental approaches were applied: LFR gene was amplified from a human testis cDNA library and recombinant LFR (rLFR) protein was produced in the expression vector Escherichia coli BL21 (DE3); human sperm membrane proteins were extracted and analysed via Western blot; the binding of LF to LFR was investigated by Far-Western blot, immunoprecipitation and autoradiography analysis and the localization of LFR on sperm surfaces was detected using immunofluorescence. LFR gene was amplified from a human testis cDNA library and the molecular weight of rLFR was 34kDa. The native LFR on human spermatozoa was a 136-kDa tetramer which was anchored to the sperm head and mid-piece through glycophosphatidylinositol. LF could bind to LFR competitively in vitro. As far as is known, this study has elucidated for the first time that LFR was expressed at the testis level, was anchored to the sperm membrane by glycophosphatidylinositol during spermatogenesis. LFR may play important roles through binding to and mediating LF.

Novel methods for the diagnosis and treatment of ejaculatory duct obstruction.

OBJECTIVES: • To investigate a new method of vas deferens radiography for ejaculatory duct obstruction (EDO). • To evaluate the effect of a procedure involving dilation of the ejaculatory duct by F9 seminal vesicoscopy. PATIENTS AND METHODS: • Twenty-two patients with EDO were diagnosed using semen analysis, semen fructose measurement, transrectal ultrasonography (TRUS) and vas deferens radiography. • Of these, 18 patients were successfully treated by dilation of ejaculatory duct using F9 seminal vesicoscopy and four patients, whose treatment was unsuccessful, were treated by transurethral resection of the ejaculatory ducts (TURED). • All patients were followed up for at least 3 months after treatment. RESULTS: • Semen analyses in all 22 patients showed oligoasthenozoospermia or azoospermia, low semen volume (0-1.9 mL), low pH level (5.6-7.0) and absent or low semen fructose. TRUS and radiography showed pure dilated seminal vesicles on both sides in three patients, partial dilated seminal vesicles in one patient, dilation of both the ejaculatory duct and seminal vesicles in ten patients, dilated seminal vesicles and a prostatic cyst in four patients, and dilated ejaculatory duct or cystic lesions without dilated seminal vesicles in the remaining four patients. • At >3-month follow-up after dilation or TURED, the semen characteristics of 18 patients were improved and sperm were present in the semen in 13 cases. Normal semen analyses were found in 7 patients and 6 patients had conceived. • Voiding urethral radiography showed that no patients who had undergone dilation by seminal vesicoscopy had urine reflux into the ejaculatory duct. Only one patient showed urine reflux into the seminal vesicle after TURED. • All patients felt that their symptoms had improved after treatment. CONCLUSIONS: • The approach to vas deferens radiography using vas deferens aspiration has proved to be an effective and safe method for EDO diagnosis. • The procedure involving the dilation of the ejaculatory duct using F9 seminal vesicoscopy is equally effective but has fewer postoperative complications than TURED.

IL-6 -174G>C polymorphism and cancer risk: a meta-analysis involving 29,377 cases and 37,739 controls.

Interleukin-6 (IL-6) is a multifunctional cytokine involved in different physiologic and pathophysiologic processes and plays important roles in the etiology of cancer. The -174G>C polymorphism of the IL-6 gene influences IL-6 transcription and has been implicated in cancer risk. However, published data have been conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 29,377 cancer cases and 37,739 controls from 50 published case-control studies was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between -174G>C polymorphism and cancer risk. Overall meta-analysis indicated that no association was found between -174G>C genotypes and cancer risk. However, the positive association was found in bladder cancer (OR=4.33, 95% CI: 1.93-9.71 for CC vs. GC, OR=2.81, 95% CI: 1.39-5.68 for CC vs. GG, and OR=2.19, 95% CI: 1.32-3.64 for CC vs. GG/GC), and among Asians (OR=2.08, 95% CI: 1.07-4.06 for CC vs. GG, and OR=2.20, 95% CI: 1.02-4.74 for CC vs. GG/GC) and Africans (OR=1.61, 95% CI: 1.07-2.42 for GC vs. GG). This meta-analysis showed the evidence that the -174G>C of the IL-6 gene was a low-penetrance susceptibility gene for bladder cancer. Further larger, preferably prospective studies are needed to confirm this relationship.

Analysis and difference of voltage-dependent anion channel mRNA in ejaculated spermatozoa from normozoospermic fertile donors and infertile patients with idiopathic asthenozoospermia.

PURPOSE: to analyze the abundance and difference of voltage-dependent anion channel (VDAC) mRNA in ejaculated spermatozoa from normozoospermic fertile donors and infertile patients with idiopathic asthenozoospermia. METHODS: high motile and low motile spermatozoa were separated respectively from ejaculates of 36 donors and 40 patients using a discontinuous Percoll gradient centrifugation. Real-Time PCR was performed to detect mRNA abundance and difference of three VDAC subtypes between two groups with different sperm motility. RESULTS: real-Time PCR demonstrated that three VDAC mRNAs were present in mature spermatozoa. The VDAC2 mRNA level in ejaculated spermatozoa of patients was significantly higher than that of donors. No significant differences of VDAC1 and VDAC3 mRNA levels were found between two groups. CONCLUSION: the high abundance of VDAC2 mRNA seemed to have a positive correlation with low sperm motility. The abnormal expression of VDAC might be related to male infertility with idiopathic asthenozoospermia.

SLC14A1 (UT-B) gene rearrangement in urothelial carcinoma of the bladder: a case report.

BACKGROUND: Bladder cancer (BC) is a common and deadly disease. Over the past decade, a number of genetic alterations have been reported in BC. Bladder urothelium expresses abundant urea transporter UT-B encoded by Slc14a1 gene at 18q12.3 locus, which plays an important role in preventing high concentrated urea-caused cell injury. Early genome-wide association studies (GWAS) showed that UT-B gene mutations are genetically linked to the urothelial bladder carcinoma (UBC). In this study, we examined whether Slc14a1 gene has been changed in UBC, which has never been reported. CASE PRESENTATION: A 59-year-old male was admitted to a hospital with the complaint of gross hematuria for 6 days. Ultrasonography revealed a size of 2.8 × 1.7 cm mass lesion located on the rear wall and dome of the bladder. In cystoscopic examination, papillary tumoral lesions 3.0-cm in total diameter were seen on the left wall of the bladder and 2 cm to the left ureteric orifice. Transurethral resection of bladder tumor (TURBT) was performed. Histology showed high-grade non-muscle invasive UBC. Immunostaining was negative for Syn, CK7, CK20, Villin, and positive for HER2, BRCA1, GATA3. Using a fluorescence in situ hybridization (FISH), Slc14a1 gene rearrangement was identified by a pair of break-apart DNA probes. CONCLUSIONS: We for the first time report a patient diagnosed with urothelial carcinoma accompanied with split Slc14a1 gene abnormality, a crucial gene in bladder.