Is switching intravesical chemotherapeutic agents beneficial in short-term recurrent high-risk non-muscle-invasive bladder tumors? A 5-year retrospective study.

OBJECTIVE: To explore if switching intravesical chemotherapeutic agents is beneficial in short-term recurrences of high-risk non-muscle-invasive bladder cancer (NMIBC) following the failure of preceding intravesical therapy. MATERIALS AND METHODS: From June 2010 to October 2015, 205 patients with NMIBC who experienced tumor recurrence within a year after receiving first-line intravesical chemotherapy (IVC) were classified into two groups. After a second complete transurethral resection (TUR) process, we immediately altered the intravesical instillation agent for 107 patients (group A). In contrast, the remaining 98 patients (group B) continued using their original intravesical instillation agent. After transurethral resection of the bladder tumor (TURBT), all patients received either an immediate instillation of epirubicin (EPI), gemcitabine (GEM), or hydroxycamptothecin (HCPT), followed by regular induction and maintenance instillations. Recurrence and progression rates were evaluated using the Chi-square test, and recurrence-free survival (RFS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. RESULTS: In this study, there was no significant difference in either the 5-year tumor recurrence or progression rates between the two groups (p > 0.05) The Kaplan-Meier plot showed no difference in progression-free or recurrence-free survival between the two groups. CONCLUSION: Switching IVC agents does not improve RFS and PFS for patients with short-term recurrent high-risk NMIBC.

Combination with vorinostat enhances the antitumor activity of cisplatin in castration-resistant prostate cancer by inhibiting DNA damage repair pathway and detoxification of GSH.

BACKGROUND: Like DNA methylation, histone modifications are considered important processes for epigenetic alterations in gene function, and abnormally high expression of histone deacetylases (HDACs) plays a key role in many human diseases. In addition to regulating the acetylation levels of histone and non-histone proteins and gene transcription, HDAC inhibitors as antitumor drugs can also affect the DNA damage repair (DDR) pathway in tumor cells. Prostate cancer (PCa) is one of the most heritable malignancies in which DDR pathway defects can be detected in a considerable proportion of cases. Such defects are more prevalent in castration-resistant prostate cancer (CRPC) and are highly enriched in metastatic lesions. There is currently evidence that DDR pathway-deficient PCa is associated with high-risk biological behaviors and response sensitivity to platinum-based chemotherapy. Platinum-based drugs have been used in multiple clinical trials as monotherapy or in combination with other chemotherapeutic agents for the treatment of CRPC. METHODS: This study evaluated the combined anticancer effect of (cisplatin) CDDP and the HDAC inhibitors vorinostat (SAHA) on three androgen-dependent cell lines PC-3, DU-145, and C4-2B in vitro. The efficacy and safety of SAHA combined with CDDP in the treatment of CRPC were further verified through animal experiments. RESULTS: The combination of the two drugs increases cytotoxic effects by increasing DNA damage. Our results showed that the SAHA could not only reduce the expression of homologous recombinant repair proteins BRCA2, BRCA1, PARP1, and RAD51, but also decrease enzymes that Reduce the key enzymes of GSH biosynthesis, GSS and GCLC, and GSTP1 which can catalyze the binding of GSH to cisplatin. The intracellular GSH level also decreased with the increase of SAHA concentration, at the same time, the content of intracellular Pt element. CONCLUSION: The combination of CDDP and SAHA can produce synergistic anticancer effects in androgen-independent PCa cells in vitro and in vivo. Our results open up a new avenue for the effective treatment of CRPC. To optimize the chemotherapy regimen for patients with advanced PCa, it is necessary to further study the molecular mechanism of platinum drugs, HDAC inhibitors, and their combined action.

Development and validation of a nomogram for predicting osteoporosis in prostate cancer patients: A cross-sectional study from China.

BACKGROUND: The specific risk factors contributing to the development of osteoporosis and the appropriate timing of treatment in Chinese prostate cancer (PCa) patients remain unclear. Our objective was to develop and validate a nomogram capable of predicting the occurrence of osteoporosis in PCa patients. METHODS: We conducted a cross-sectional study with PCa patients attending the Second Hospital of Tianjin Medical University, collecting data from June 2021 to February 2023. The patients were divided into training and validation sets in a 7:3 ratio. The LASSO regression was used to identify the most relevant predictive variables, and the multivariable logistic regression was used to construct the nomogram. The nomogram's performance was validated through receiver operating characteristic (ROC) curves, C-index, calibration curves, and decision curve analysis (DCA) in both the training and validation sets. RESULTS: We collected data from a total of 596 patients and then constructed the nomogram using age, body mass index, hemoglobin, vitamin D3, testosterone, and androgen deprivation therapy duration. The C-index of the nomogram was 0.923 in the training set and 0.859 in the validation set. The nomogram showed good consistency in both sets. DCA demonstrated the clinical benefit of the nomogram across various prediction thresholds. Furthermore, a separate nomogram was constructed to predict bone loss in patients undergoing ADT, exhibiting equally favorable diagnostic performance and clinical benefit. CONCLUSION: This study constructed two reliable nomograms to predict osteoporosis and bone loss, integrating personal health information and PCa-specific treatment data. These nomograms offer an easy and individualized approach to predict the occurrence of osteoporosis and bone loss in PCa patients.

Targeted micelles with chemotherapeutics and gene drugs to inhibit the G1/S and G2/M mitotic cycle of prostate cancer.

BACKGROUND: Chemotherapy and gene therapy are used in clinical practice for the treatment of castration-resistant prostate cancer. However, the poor efficiency of drug delivery and serious systemic side effects remain an obstacle to wider application of these drugs. Herein, we report newly designed PEO-PCL micelles that were self-assembled and modified by spermine ligand, DCL ligand and TAT peptide to carry docetaxel and anti-nucleostemin siRNA. RESULTS: The particle size of the micelles was 42 nm, the zeta potential increased from - 12.8 to 15 mV after grafting with spermine, and the optimal N/P ratio was 25:1. Cellular MTT experiments suggested that introduction of the DCL ligand resulted in high toxicity toward PSMA-positive cells and that the TAT peptide enhanced the effect. The expression of nucleostemin was significantly suppressed in vitro and in vivo, and the tumour-inhibition experiment showed that the dual-drug delivery system suppressed CRPC tumour proliferation. CONCLUSIONS: This targeted drug delivery system inhibited the G1/S and G2/M mitotic cycle via synergistic interaction of chemotherapeutics and gene drugs.

Association between obstructive sleep apnea syndrome and nocturia: a meta-analysis.

BACKGROUND: The relationship between obstructive sleep apnea (OSA) and the risk of nocturia remains unclear. Therefore, we sought to identify whether or not OSA affects the incidence of nocturia. METHODS: A thorough literature search was executed in September 1st 2018 from PubMed, Web of Science database, and Embase. We used DerSimonian and Laird random-effects to calculate the pooled relative ratio (RR). RESULTS: Total of 13 studies met inclusion criteria and in total comprised, 406 patients and 9518 controls. There was a significant association between OSA and the risk of nocturia (RR = 1.41, 95% CI 1.26-1.59). Through subgroup analysis by different severity of OSA, we found patients who had severe OSA were at high risk of nocturia. Through another subgroup analysis, we found a statistically significant association between OSA and risk of nocturia in the men (RR = 1.487, 95% CI 1.087-2.034, P = 0.013). However, there was no significant relationship between OSA and nocturia in the women (RR = 1.537, 95% CI 0.831-2.842, P > 0.05). Subgroup analysis of different diagnostic methods indicated that OSA was significantly associated with the risk of nocturia regardless what method was used to diagnose OSA (P < 0.05). CONCLUSION: The findings suggest that men with OSA have a high incidence of nocturia. A large multicenter study may be useful to explore the relationship between OSA and nocturia, in order to elucidate its causes.

Impact of positive surgical margin location and perineural invasion on biochemical recurrence in patients undergoing radical prostatectomy.

OBJECTIVE: To estimate the prognostic value of positive surgical margins (PSM) location and perineural invasion (PNI) for biochemical recurrence (BCR) in patients undergoing radical prostatectomy (RP). METHODS: All men with prostate cancer (PCa) who received RP in the second hospital of Tianjin Medical University from 2014 to 2018 were retrospectively identified. All patients met the following criteria: no neoadjuvant or adjuvant treatment, absence of lymph node invasion, or distant metastasis confirmed by surgery or imaging. Comparisons were made between cases with only apex positive (AM), isolated nonapical positive (OM), multiple positive (MM), and negative surgical margins (NSM). Patients were also subdivided according to the Gleason score and pathological tumor stage for analysis. RESULTS: A total of 416 patients available for analysis, of which 132 (31.7%) were PSM, 43 were AM, 37 were OM, and 52 were MM at a median follow-up of 27 months. The PNI was in 30.5% of patients. BCR occurred in 22.6% of patients during follow-up. Both AM and MM were noticed to be independent predictors of BCR with a hazard ratio of 4.192 (95% CI 2.185-8.042; p < 0.001) and 2.758 (95% CI 1.559-4.880; p < 0.001), respectively, when compared to NSM. Though the correlation was significant in univariate analysis, PNI was not an independent risk factor for BCR (p = 0.369). Subgroup analyses suggested that MM was not particularly predictive for BCR in the Gleason score < 8. The hole Cox regression model for the C-index was 0.843 CONCLUSIONS: PSM location was a significant independent predictor of BCR in PCa, especially in patients with AM or MM, while PNI is a non-independent risk factor. Compared with other locations, AM has a higher BCR risk.

Androgen Deprivation Therapy and the Risk of Stroke in Patients with Prostate Cancer: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: The aim of this article was to review the association between androgen deprivation therapy (ADT) and the risk of stroke in patients with prostate cancer (PC). Thus, we performed this study to understand the impact of ADT on the incidence of stroke in PC patients. METHODS: A comprehensive literature search was performed in June 2019 based on PubMed, EMBASE, and Web of science databases. Pooled rate ratio (RR), hazard ratio (HR), and their 95% confidence intervals (95% CIs) were calculated with a DerSimonian and Laird random effects. RESULT: A total of 239,099 patients from 10 studies were included in this analysis. There was no significant association in pooled RR analysis. Pooled HR analysis showed that ADT treatment increased the risk of stroke (HR = 1.129, 95% CI: 1.019-1.251, p = 0.02). In a subgroup analysis of RR results, we found that different ADT treatments had no significant effect on increasing the risk of stroke. And in the subgroup analysis of HR results, only PC patients treated with gonadotropin-releasing hormone (GnRH) agonists, orchiectomy, or oral antiandrogen had significantly higher risk of stroke. In addition, we observed the result from another comparison that PC patients treated with GnRH agonists combined with oral antiandrogens might have a lower risk of stroke compared with using GnRH agonists alone. CONCLUSION: Our results showed that GnRH agonists, orchiectomy, or oral antiandrogen might play an important role in the incidence of stroke. We still need further studies to clarify the role of ADT in the increased risk of stroke.

The association between androgen receptor splice variant 7 status and prognosis of metastatic castration-resistant prostate cancer: A systematic review and meta-analysis.

Recent studies have found that metastatic castrated-resistant prostate cancer (mCRPC) with positive androgen receptor splice variant 7 (AR-V7) may have poor prognosis during endocrine or chemotherapy treatment, but the specific mechanism was still unclear. We had finished literature search in March 2019 from PubMed, Web of Science database, and Embase. The final results were presented in this research. The pooled results showed that AR-V7 status predicted pooled PSA-PFS (HR = 4.31, 95% CI: 2.57-7.24, p < .001), rPFS (HR = 2.39, 95% CI: 1.28-4.48, p = .006) and OS (HR = 4.27, 95% CI: 3.22-5.66, p < .001) in mCRPC patients after endocrine or chemotherapy treatment. Subgroup analysis of different treatments revealed that mCRPC patients treated with chemotherapy had significant association between positive AR-V7 and OS (HR = 2.82, 95% CI: 1.72-4.62, p < .001), and also during endocrine therapy (HR = 4.78, 95% CI: 3.33-6.86, p < .001). Our study demonstrated that AR-V7-positive mCRPC patients may have worse prognosis. AR-V7 may be an independent prognostic factor for endocrine therapy or chemotherapy in patients with mCRPC.

hnRNPM, a potential mediator of YY1 in promoting the epithelial-mesenchymal transition of prostate cancer cells.

BACKGROUND: With the popularity of serum prostate-specific antigen (PSA) screening, the number of newly diagnosed prostate cancer (PCa) patients is increasing. However, indolent or invasive PCa cannot be distinguished by PSA levels. Here, we mainly explored the role of heterogeneous nuclear ribonucleoprotein M (hnRNPM) in the invasiveness of PCa. METHODS: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis was used to detect the expressions of hnRNPM in PCa and benign prostate hyperplasia (BPH) tissues as well as in PCa cell lines. Immunohistochemistry was applied to detect the hnRNPM or Yin Yang 1 (YY1) expression in BPH, prostate adenocarcinoma (ADENO) and neuroendocrine prostate cancer (NEPC) tissues. After aberrant, the expression of hnRNPM in C4-2 and PC3 cells, the changes of cell migration and invasion were observed through wound-healing and transwell assays. We also predicted the transcription factor of hnRNPM through databases, then verified the association of hnRNPM and YY1 using chromatin immunoprecipitation (ChIP) and luciferase assays. RESULTS: The expression level of hnRNPM is gradually reduced in BPH, ADENO, and NEPC tissues and it is less expressed in more aggressive PCa cell lines. Overexpression of hnRNPM can significantly reduce Twist1 expression, which inhibits the migration and invasion of PCa cells in vitro. In PCa cells, overexpression of YY1 can promote epithelial-mesenchymal transition by reducing hnRNPM expression. Furthermore, this effect caused by overexpression of YY1 can be partially attenuated by simultaneous overexpression of hnRNPM. CONCLUSIONS: Our study demonstrates that hnRNPM negatively regulated PCa cell migration and invasion, and its expression can be transcriptionally inhibited by YY1. We speculated that hnRNPM may be a biomarker to assist in judging the aggressiveness of PCa.

Could aspirin be a lifesaver for prostate cancer patients in prostate cancer-specific mortality?: an update systematic review and meta-analysis.

BACKGROUND: Currently, clinical studies on the prognosis of prostate cancer (PC) taking aspirin were developing, but the precise mechanism of aspirin on tumor cells was still unclear. In addition, the conclusion that aspirin can improve the prognosis of PC patients continues to be controversial. Therefore, we collected comprehensive literatures and performed our study to explore the prognostic effect of aspirin on PC. METHODS: A comprehensive literature search was performed in April 2019 based on PUBMED. EMBASE. Hazard Ratio (HR) as well as its 95% confidence interval (CIs) for prostate cancer specific mortality (PCSM) was extracted from eligible studies. RESULT: A total of 10 eligible articles were used in our study. The pooled results showed that PC patients who used aspirin or taking aspirin did not have lower PCSM than those who had not used (HR =0.89, 95% CI: 0.73-1.08, P>0.05). In subgroup analysis, we found that taking aspirin before diagnosis of prostate cancer and taking aspirin after diagnosis of prostate cancer did not have significant association with PCSM. (pre-diagnostic use, HR = 0.88, 95% CI: 0.72-1.06; post-diagnosis use, HR = 0.88, 95% CI: 0.67-1.17). In addition, we found no significant association between aspirin use or its duration and the risk of PCSM. Another important result demonstrated that aspirin use was not associated with risk of PSCM in either high risk (T ≥ 3 and/or Gleason score ≥ 8) or low risk PC patients(low-risk PC, HR = 1.05, 95% CI: 0.81-1.35; high-risk PC, HR = 0.97, 95% CI: 0.75-1.24). CONCLUSION: Our results demonstrated that there was no significant association between aspirin use and the risk of PCSM. At the same time, the dosage and duration of aspirin use had no statistical influence on the risk of PCSM in high/low risk PC. Further studies are needed to confirm the findings.

Association between male pattern baldness and testicular germ cell tumor: a meta-analysis.

BACKGROUND: The relationship between male pattern baldness and incidence of testicular cancer remains inconclusive. Hence, we performed the present meta-analysis based on all eligible case-control studies. METHODS: A comprehensive literature search was performed in July 30th 2018 based on PUBMED, EMBASE and Web of science database. Pooled odds ratio(OR) and its 95% confidence intervals (95% CIs) was calculated with a DerSimonian and Laird random-effects. RESULTS: The pooled results were included in this meta-analysis. Overall, We have demonstrated statistically signification between baldness(any pattern) and testicular cancer was identified (OR: 0.61, 95% CI:0.50-0.74). There was no obvious heterogeneity across included studies (P = 0.22 for heterogeneity, I2 = 30%). When subgroup analysis by types of baldness, We found a statistically significant association was observed that baldness(I-VII) might become a protective factor for the risk of testicular germ cell tumor(TGCT). There was no definite connection between alopecia and the different types of TGCT. CONCLUSION: Individuals with any pattern baldness may have a decreased risk of testicular cancer, all of analyses studies are warranted to confirm our preliminary findings. According to subgroup analysis of different hair loss grades, we found that 2 stage(II) hair loss can decrease more strongly testicular cancer risk than any other grades. Despite of our findings, We still need further researches to advance knowledge in this field.

The Specific Choice of Transrectal Ultrasound-Guided Prostate Biopsy Scheme Based on Prostate Specific Antigen and Prostate Specific Antigen Density.

BACKGROUND Although magnetic resonance imaging (MRI)-targeted biopsy and saturation biopsy can improve the accuracy of prostate biopsy, transrectal ultrasound (TRUS)-guided prostate biopsy is still the cornerstone for diagnosis of prostate cancer. However, it is not clear whether it is necessary to perform the same TRUS-guided biopsy scheme for patients with different prostate specific antigen (PSA) or prostate specific antigen density (PSAD) levels. The purpose of this study was to evaluate the optimal core number for specific suspected prostate cancer patients. MATERIAL AND METHODS There were 398 patients who underwent 12-core biopsy scheme, who were included in this retrospective analysis. The 12-core scheme incorporated a classic sextant scheme and 4-core biopsies from the base and middle regions bilaterally. The cancer detection rates of patients with different PSA or PSAD levels between the 12-core, sextant, 4-core, and 2-core biopsy were compared. RESULTS The differences in cancer detection rates between the 12-core biopsy scheme and the sextant biopsy scheme were significant in patients with PSA <20 ng/mL or PSAD <0.3. There were no differences in the cancer detection rates between the 12-core biopsy scheme and the 4-core biopsy scheme in patients with PSA ≤50 ng/mL or PSAD ≤1.0. There were significant differences between 12-core and 2-core scheme when PSA ≤70 ng/mL or PSAD ≤1.5. CONCLUSIONS We recommend that the 12-core biopsy should be used for patients with PSA <20 ng/mL or PSAD <0.3. The biopsy scheme in patients with PSA 20-50 ng/mL or PSAD 0.3-1.0 should be considered in combination with DRE and MRI. For patients with PSA >50 ng/mL or PSAD >1.0, we recommend 6-core or 4-core biopsy by comprehensively considering multiple factors. The 2-core biopsy is recommended for patients with PSA >70 ng/mL or PSAD >1.5.

[Apoptosis induced by transferring cytosine deaminase suicide gene into kinds of cancer cells with novel polyamidoamine dendrimers].

This study demonstrates efficacy of a novel polyamidoamine dendrimers(PAMAM dendrimers) with pentaerythritol derivatives as the core(G5 PD dendrimer) in deliver of the cytosine deaminase(CD) gene and EGFP gene fusion plasmid into different tumor cell lines to induce apoptosis. The physical and chemical properties of G5 PD dendrimers in terms of DNA complexation, particulate properties and transfection efficiencies were investigated and compared with commercial gene vectors PEI 25 k Da. The optimum ratio of G5 PD dendrimer complexed with plasmid DNA was 0.2∶1, and the particle size of the complex was(100 ± 5) nm. Compared with the commercial gene carriers PEI, G5 PD dendrimer exhibited a higher transfection efficiency at the weight ratio of 1∶1 in three different cell lines, given the fact that PEI are different from PAMAM dendrimers in terms of molecular structure. Furthermore, the cytotoxicity assays of the cell lines transfected with G5 PD dendrimer/p CD-EGFP-N1 followed by exposure to various concentrations of 5-fluorocytosine(5-FC) also showed that the transfected cell lines could generate a very low amount of 5-FC to 5-fluorouracil(5-FU) in a short period of time, which indicating the high expression level of CD gene in the cell line. These results indicate that the CD/5FC system of G5 PD dendrimer has an excellent efficacy in gene delivery.

An ultrasound image navigation robotic prostate brachytherapy system based on US to MRI deformable image registration method.

OBJECTIVE: This paper describes an ultrasound image navigation robotic prostate brachytherapy system. It uses a 2D ultrasound (US) probe rigidly fixed to a robotic needle insertion mechanism. Combined with the US probe registration and image registration, this system will help to navigate the prostate brachytherapy to increase the inserting accuracy. SUBJECTS AND METHODS: The novelty of the system is that after the US probe registration using an improved iterative closest point (ICP) registration method, the initial registration for the magnetic resonance imaging (MRI) and US image can be completely automatically. Moreover, a deformable registration method based on statistical measurement was proposed to register US to MRI images intra-operatively. RESULTS: The 6-degree of freedom (6-DOF) of robot and ultrasound probe are calibrated together with an accuracy of 0.9mm, allowing the needles to be precisely inserted to the seed targets after the image registration. Experiments were conducted by using US/MRI images, capturing from patients. Results showed that the accuracies of probe registration and US-MRI registration were: 0.44±0.12mm and 2.30±0.41mm, respectively. CONCLUSION: With the help of this robotic system, the accuracy and the costing of time for prostate brachytherapy will greatly improve.

Elf5 inhibits TGF-ß-driven epithelial-mesenchymal transition in prostate cancer by repressing SMAD3 activation.

BACKGROUND: The epithelial-mesenchymal transition (EMT) has been associated with the acquisition of migration, invasiveness, and metastasis traits. During tumor progression, EMT can be induced by transforming growth factor-ß (TGF-ß) signal that epithelial cells receive from their microenvironment. However, the master regulatory controls on TGF-ß-EMT axis are not understood. METHODS: The protein expression in human specimens was measured by immunohistochemical staining. E74-like factor 5 (Elf5) was silenced by short interfering RNAs in LNCaP cells and stably overexpressed by HA-tagged Elf5 cDNAs in 22Rv1 cells. These cells were used to study migration and anchorage-independent growth. RESULTS: Our data reveal that Elf5 results in the failure of mesenchymal morphogenesis, upregulation of EMT markers, spheres formation, and migration in the presence of TGF-ß. Furthermore, Elf5 blocks TGF-ß signaling, through decreasing drosophila mothers against decapentaplegic protein (SMAD3) activation by binding to it, one of the major effector of TGF-ß-induced EMT. Moreover, Elf5 can serve as a prognostic marker of metastasis-free survival in patients with TGF-ß-positive prostate cancer. CONCLUSIONS: Elf5 expression is inversely correlated with EMT. Elf5 inhibits TGF-ß-driven EMT via repressing SMAD3 phosphorylation in prostate cancer cells. In addition, Elf5 can be used as a biomarker of metastasis-free survival in patients with TGF-ß-positive prostate cancer.

Is Lipopolysaccharide-Induced Lipid Metabolism Disorder in Testis of Rats a Consequence of Plasma Lipid Changes?

Purpose: The systemic infection and inflammation can result in testes injury, whereas the exact mechanism is unknown. The lipid metabolism has a dual impact on controlling metabolism and inflammation, which is a potential pathway. The objective of this study was to determine if changes in plasma lipids during lipopolysaccharide (LPS)-induced systemic inflammation affect the dysregulation of testes lipid metabolism. Materials and Methods: LPS (5 mg/kg) was used to induce systemic inflammation in rats after a single intraperitoneal injection. After 4 weeks, the rats were sacrificed, and the serum and testes were used for laboratory measurements and histology examination. Plasma and testis were used for lipidomics analysis based the liquid chromatography-mass spectrometry. Spearman rank correlation analysis was used to compare the correlation of differential lipids in phospholipids, glycerolipids, and sphingolipids between testis and plasma. Results: LPS raised the levels of cytokines in serum and testis, decreased the activities of antioxidant enzymes, increased the levels of lipid peroxidation products, and damaged testis tissue. In testis and plasma, 146 and 401 differential lipids, mostly phosphatidylcholine, phosphatidylethanolamine an so on, were found in comparison to the control group. Correlation analysis produced a total of 2528 correlation coefficients, 1150 of which were P<0.05 and accounted for 45.49%. Conclusion: The changes of lipid composition and content in the testis are related to cytokine overload and oxidative stress. Testis lipid metabolism disorders caused by LPS-induced systemic inflammation are lack of a correlation with plasma lipid changes, and are likely owing to interference with the testis itself.

Prognostic value of GARS in bladder cancer and its role in the tumor microenvironment.

Background: Bladder cancer (BC), as a common type of cancer, has a poor prognosis, also some common invasive prognostic or therapeutic markers are difficult to obtain, which makes further treatment of BC difficult. Glycyl-tRNA synthetase (GARS), as one of the aminoacyl-tRNA synthetases that charge tRNAs with their cognate amino acids, has been identified as a target in many diseases, including tumors. Methods: Bioassay analysis revealed that GARS was in high expression in most cancer tissues. The expression of GARS gene in BC tissues could assess the prognosis of BC patients, and the expression in urinary extracellular vesicles (uEVs) of patients was positively correlated with the expression in tissues. In addition to this, we analyzed GARS-related differential gene expression, copy number variation (CNV) and mutation profiles, potential biological functions, immune cell infiltration and drug sensitivity. In vivo and vitro tumorigenic experiments were performed to validate the function of GARS. Single-cell data were used to further analyze its role in the microenvironment. Results: In our study, we found that GARS was highly expressed in 30 cancer tissues including BC, and high GARS expression was negatively correlated with the prognosis of BC patients. To address this phenomenon, we analyzed the differential genes between high and low GARS groups by enrichment analysis, and identified the biological signaling pathways that were mainly enriched for their functions, and found that the enrichment was found in immune-related signaling pathways and regulation of cell-cell adhesion. Then we found that GARS was positively associated with immune cell infiltration in BC, and some common immune checkpoints were significantly overexpressed in the GARS-high group. Besides, we found that GARS was enriched in myofibroblasts in the tumor microenvironment, and the enrichment was positively correlated with epithelial-mesenchymal transition (EMT)-related genes. This study also showed a positive correlation between GARS and BC RNA stemness. Patients in the GARS-high group had considerably higher rates of P53 and Titin (TTN) mutations than those in the GARS-low group. Drug Sensitivity analysis screened for drugs that were more sensitive to GARS-high patients. Further, we found that knockdown of GARS significantly inhibited the proliferation, migration and invasion ability both in vivo and in vitro. Finally, we found that in patients with high GARS the expression in uEVs was also at a high level. Conclusions: In summary, this study provided evidence that GARS can be used as a prognostic and therapeutic marker for BC, we can detect GARS in uEVs instead of tissue, to provide a new, simple, noninvasive way to obtain prognostic and therapeutic markers for BC patients.

[Corrigendum] Cripto­1 promotes epithelial­mesenchymal transition in prostate cancer via Wnt/ß­catenin signaling.

Following the publication of the above article, an interested reader drew to the authors' attention that the ß­actin control blots featured in Figs. 5A and 6A appeared to be strikingly similar. Upon examining their original data, the authors have realized that the ß­actin blots for Fig. 5A were inadvertently chosen incorrectly. The corrected version of Fig. 5 is shown opposite. Note that the error made in uploading the incorrect version of this figure did not affect the overall conclusions reported in the paper. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this. They also apologize to the readership for any inconvenience caused. [Oncology Reports 1521­1528, 2017; DOI: 10.3892/or.2017.5378].

Long noncoding RNA MEG3 regulates cell proliferation and apoptosis by disrupting microRNA-9-5p-mediated inhibition of NDRG1 in prostate cancer.

BACKGROUND: Long noncoding RNA MEG3 has been described to be involved in the regulation of gene expression and cancer progression. However, the role of lncMEG3 in prostate cancer (PCa) remains largely uncharted. METHODS: Differential expression of lncMEG3 was identified in PCa tissues using RNA-sequencing analysis. qRT-PCR was performed to examine the level of lncMEG3. Additionally, cellular fractionation and fluorescent in situ hybridization techniques were employed to determine the localization. Subsequently, functional assays were conducted to evaluate the impact of lncMEG3 and miR-9-5p on PCa proliferation and apoptosis in vitro and in vivo. The interaction between lncMEG3 and miR-9-5p was confirmed using RNA immunoprecipitation. Moreover, luciferase reporter assays were also utilized to investigate the relationship between miR-9-5p and NDRG1. RESULTS: We observed downregulation of lncMEG3 in PCa cells and tissues. Patients with lower levels of lncMEG3 had a higher likelihood of experiencing biochemical recurrence. Overexpression of lncMEG3 resulted in the inhibition of PCa cell proliferation and the promotion of apoptosis. Moreover, lncMEG3 is competitively bound to miR-9-5p, preventing its inhibitory effect on the target gene NDRG1. This ultimately led to the inhibition of PCa cell proliferation and the promotion of apoptosis. Furthermore, increasing lncMEG3 levels also demonstrated inhibitory effects on PCa proliferation and promotion of apoptosis in vivo. CONCLUSIONS: Our findings uncover a crucial role for lncMEG3 in inhibiting PCa proliferation and promoting apoptosis through disruption of miR-9-5p-mediated inhibition of NDRG1.

Comparison of Regional Saturation Biopsy, Targeted Biopsy, and Systematic Biopsy in Patients with Prostate-specific Antigen Levels of 4-20 ng/ml: A Prospective, Single-center, Randomized Controlled Trial.

BACKGROUND: Despite the use of multiparametric magnetic resonance imaging (mpMRI)-guided targeted biopsy (TB) to identify suspicious prostate lesions, it may still miss clinically significant prostate cancer (csPCa) or result in false-negative findings. Recent evidence suggests that combining biopsies taken from within and around magnetic resonance imaging (MRI) lesions can improve the detection of csPCa. OBJECTIVE: This study aimed to compare the diagnostic performance of the regional saturation biopsy (RSB) method, involving template-based nine-core biopsies for suspected regions, with that of the MRI-directed TB and/or the systematic biopsy (SB) methods in biopsy-naïve patients with prostate-specific antigen (PSA) levels ranging from 4 to 20 ng/ml. DESIGN, SETTING, AND PARTICIPANTS: A prospective, single-center, randomized controlled trial included 434 biopsy-naïve patients with suspected lesions on mpMRI and PSA levels between 4 and 20 ng/ml (from January 2022 to July 2023). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The detection rates of csPCa for the RSB, TB, and SB methods were analyzed using the McNemar test for intrapatient comparisons. The Fisher's exact test was used for comparisons between RSB and TB. RESULTS AND LIMITATIONS: The RSB approach yielded a significantly higher detection rate of csPCa than both the TB approach (44.1% vs 31.8%, p = 0.01) and the SB approach (44.1% vs 34.1%, p = 0.03). The RSB approach exhibited a comparable detection rate of csPCa (44.1% vs. 40.7%, p = 0.3) to the combined approach (TB + SB), while requiring fewer biopsy cores and a higher positive core number to avoid sampling the entire prostate gland (32.7% vs 18.3%, p < 0.001). Upon conducting a whole-mount histopathological analysis, it was observed that the RSB approach successfully identified 97% (32 out of 33) of the prostate cancer foci as the index lesion, whereas only 59.18% (29 out of 49) were classified as index lesions using the SB approach. Furthermore, mpMRI underestimated the average diameter of histological tumor size by a median of 0.76 cm, highlighting the importance of an optimal biopsy area for the RSB procedure. CONCLUSIONS: For patients with suspected lesions on mpMRI and PSA levels between 4 and 20 ng/ml, the RSB approach has shown improved detection of clinically significant prostate cancer, accurately identifying index lesions, and minimizing biopsy cores compared with the MRI-directed TB and SB approaches. PATIENT SUMMARY: For patients with suspected lesions on multiparametric magnetic resonance imaging and prostate-specific antigen levels between 4 and 20 ng/ml, the regional saturation biopsy method provides enhanced detection of clinically significant prostate cancer, as well as precise identification of index lesions, surpassing both magnetic resonance imaging-directed targeted biopsy and the systematic biopsy method.