Osr2 functions as a biomechanical checkpoint to aggravate CD8+ T cell exhaustion in tumor.

Alterations in extracellular matrix (ECM) architecture and stiffness represent hallmarks of cancer. Whether the biomechanical property of ECM impacts the functionality of tumor-reactive CD8+ T cells remains largely unknown. Here, we reveal that the transcription factor (TF) Osr2 integrates biomechanical signaling and facilitates the terminal exhaustion of tumor-reactive CD8+ T cells. Osr2 expression is selectively induced in the terminally exhausted tumor-specific CD8+ T cell subset by coupled T cell receptor (TCR) signaling and biomechanical stress mediated by the Piezo1/calcium/CREB axis. Consistently, depletion of Osr2 alleviates the exhaustion of tumor-specific CD8+ T cells or CAR-T cells, whereas forced Osr2 expression aggravates their exhaustion in solid tumor models. Mechanistically, Osr2 recruits HDAC3 to rewire the epigenetic program for suppressing cytotoxic gene expression and promoting CD8+ T cell exhaustion. Thus, our results unravel Osr2 functions as a biomechanical checkpoint to exacerbate CD8+ T cell exhaustion and could be targeted to potentiate cancer immunotherapy.

Comparisons of mpMRI, 68Ga-PSMA PET/CT and mpMRI combined with 68Ga-PSMA PET/CT in diagnosing prostate cancer based on tumor detection, localization and staging.

PURPOSE: To evaluate the diagnostic ability of mpMRI, 68Ga-PSMA PET/CT and mpMRI combined with 68Ga-PSMA PET/CT in detecting and localizing lesions, and further clarify the accuracy of these examinations in tumor staging. METHODS: Seventy patients who underwent mpMRI, 68Ga-PSMA PET/CT and radical prostatectomy were enrolled. The abilities to detect index and clinically significant lesions by three examinations were compared. We further evaluated the ability of these examinations to localize lesions to the superior, inferior, anterior, posterior, left and right halves of the prostate and analyzed their accuracy in local and lymph node staging. RESULTS: There were no significant differences among mpMRI, 68Ga-PSMA PET/CT and mpMRI combined with 68Ga-PSMA PET/CT in their ability to detect index (p = 0.48, p = 0.23 and p = 0.07) and clinically significant lesions (p = 0.30, p = 0.29 and p = 0.06) or to localize lesions in six half divisions of the prostate. With postoperative pathology as reference, both mpMRI (p = 0.10) and mpMRI combined with 68Ga-PSMA PET/CT (p = 0.10) can accurately assess the local staging of prostate cancer. However, 68Ga-PSMA PET/CT underestimates the local staging of prostate cancer (p < 0.01). Regarding lymph node staging, the three types of examination showed no significant differences compared to postoperative pathology (p = 0.63, p = 0.51 and p = 0.14). CONCLUSIONS: With postoperative pathology as reference, 68Ga-PSMA PET/CT underestimates the local tumor staging. MpMRI combined with 68Ga-PSMA PET/CT has no obvious advantages in detecting, localizing or staging prostate cancer compared with mpMRI.

Development of a nomogram combining multiparametric magnetic resonance imaging and PSA-related parameters to enhance the detection of clinically significant cancer across different region.

OBJECTIVE: Prostate cancer (PCa) is the most prevalent cancer among males. This study attempted to develop a clinically significant prostate cancer (csPCa) risk nomogram including Prostate Imaging-Reporting and Data System (PI-RADS) score and other clinical indexes for initial prostate biopsy in light of the different prostate regions, and internal validation was further conducted. PATIENTS AND METHODS: A retrospective study was performed including 688 patients who underwent ultrasound-guided transperineal magnetic resonance imaging fusion prostate biopsy from December 2016 to July 2019. We constructed nomograms combining PI-RADS score and clinical variables (prostate-specific antigen [PSA], prostate volume (PV), age, free/total PSA, and PSA density) through univariate and multivariate logistic regression to identify patients eligible for biopsy. The performance of the predictive model was evaluated by bootstrap resampling. The area under the curve (AUC) of the receiver-operating characteristic (ROC) analysis was appointed to quantify the accuracy of the primary nomogram model for csPCa. Calibration curves were used to assess the agreement between the biopsy specimen and the predicted probability of the new nomogram. The χ2 test was also applied to evaluate the heterogeneity between fusion biopsy and systematic biopsy based on different PI-RADS scores and prostate regions. RESULTS: A total of 320 of 688 included patients were diagnosed with csPCa. csPCa was defined as Gleason score ≥7. The ROC and concordance-index both presented good performance. The nomogram reached an AUC of 0.867 for predicting csPCa at the peripheral zone; meanwhile, AUC for transitional and apex zones were 0.889 and 0.757, respectively. Statistical significance was detected between fusion biopsy and systematic biopsy for PI-RADS score >3 lesions and lesions at the peripheral and transitional zones. CONCLUSION: We produced a novel nomogram predicting csPCa in patients with suspected imaging according to different locations. Our results indicated that PI-RADS score combined with other clinical parameters showed a robust predictive capacity for csPCa before prostate biopsy. The new nomogram, which incorporates prebiopsy data including PSA, PV, age, and PI-RADS score, can be helpful for clinical decision-making to avoid unnecessary biopsy.

Identification of UAP1L1 as a critical factor for prostate cancer and underlying molecular mechanism in tumorigenicity.

BACKGROUND: Prostate cancer is the second most common cancer in men, and some new target genes are needed to predict the risk of prostate cancer progression and the treatment. METHODS: In this study, the effects of UAP1L1 (UAP1-like-1) on prostate cancer were investigated by detecting the proliferation, migration, invasion and apoptosis of prostate cancer cells in vitro using MTT, wound healing, Transwell and flow cytometry assay, and the tumor growth in vivo. The downstream genes and pathways of UAP1L1 were explored using Ingenuity Pathway Analysis (IPA), and screened by qRT-PCR and western blot. The effects of CDCA8 on prostate cancer cells were also verified in vitro, which was through detecting the change of proliferation, migration, invasion and apoptosis of prostate cancer cells after CDCA8 knockdown. RESULTS: The results indicated that UAP1L1 promoted the proliferation, migration and invasion of prostate cancer cells, which was inhibited by downregulating CDCA8. Furthermore, the promotion of CDCA8 knockdown on cell apoptosis was reduced when UAP1L1 was simultaneously overexpressed. CONCLUSIONS: In conclusion, the results in this study revealed that UAP1L1 promoted the progression of prostate cancer through the downstream gene CDCA8.

The characteristics and spatial distributions of prostate cancer in autopsy specimens.

BACKGROUND: The characteristics of prostate cancer on autopsy and early-stage prostate cancer are identical. Using autopsy specimens, we analysed prostate cancer characteristics and clarified the spatial distributions of lesions. METHOD: We obtained prostate specimens from Chinese donors without a prostate cancer diagnosis and analyzed prostate cancer pathological characteristics on autopsy by whole-mount sampling. We determined the distributions of lesions in horizontal and vertical dimensions. The horizontal dimension included four horizontal quadrants (left-anterior, left-posterior, right-anterior, and right-posterior quadrants), the peripheral zone, and the transition zone. RESULT: The overall positive rate of prostate cancer among 113 specimens was 35.4%. There were 73 lesions in 40 prostates with prostate cancer. The positive rates of lesions in the left-anterior, left-posterior, right-anterior, and right-posterior quadrants were 24.7% (18/73), 27.4% (20/73), 26.0% (19/73), and 21.9% (16/73), respectively. The positive rate of prostate cancer was 74% in the areas between the apex above 0.5-0.8 cm and the middle slice. There were 22 (30.1%) and 51 (69.9%) lesions in the superior and inferior half of the prostate. There were no significant differences in the median volume and Gleason grade group between the superior and inferior half (p = .876 and p = .228). CONCLUSION: In the horizontal dimension, the positive rate of prostate cancer was consistent in the four quadrants. Prostate cancer mainly originated from the areas between the apex above 0.5-0.8 cm and the middle slice. Compared with the superior half, the inferior half of the prostate had a higher positive rate but the same lesion characteristics.

Long non-coding RNA ADAMTS9-AS1 inhibits the progression of prostate cancer by modulating the miR-142-5p/CCND1 axis.

BACKGROUND: Emerging evidence has implied the importance of long non-coding RNAs in cancer development, including prostate cancer (PCa). Bioinformatic analyses have identified that ADAMTS9-AS1 may play a role in cancer progression. METHODS: A quantitative real-time polymerase chain reaction was conducted to measure ADAMTS9-AS1 expression level at messenger RNA level. In vitro functional analyses were performed to investigate cell behaviors status under different conditions. Moreover, rescue assays were conducted to explore the potential mechanisms of ADAMTS9-AS1 in PCa progression. RESULTS: ADAMTS9-AS1 expression is down-regulated in PCa. Forcing ADAMTS9-AS1 expression impedes PCa cell proliferation via initiating cell apoptosis. Importantly, microRNA-142-5p (miR-142-5p) mimic and small-interfering RNA targeting cyclin D1 (CCND1, si-CCND1) could attenuate the inhibitory effects of ADAMTS9-AS1 overexpression on PCa cell growth. CONCLUSIONS: Collectively, our results indicate that ADAMTS9-AS1 suppresses PCa progression by regulating the miR-142-5p/CCND1 axis, which provides a new mechanism for the progression of PCa.

Development and internal validation of a prediction model of prostate cancer on initial transperineal template-guided prostate biopsy.

BACKGROUND: Due to the invasiveness of prostate biopsy, a prediction model of the individual risk of a positive biopsy result could be helpful to guide clinical decision-making. Most existing models are based on transrectal ultrasonography (TRUS)-guided biopsy. On the other hand, transperineal template-guided prostate biopsy (TTPB) has been reported to be more accurate in evaluating prostate cancer. The objective of this study is to develop a prediction model of the detection of high-grade prostate cancer (HGPC) on initial TTPB. RESULT: A total of 1352 out of 3794 (35.6%) patients were diagnosed with prostate cancer, 848 of whom had tumour with Grade Group 2-5. Age, PSA, PV, DRE and f/t PSA are independent predictors of HGPC with p < 0.001. The model showed good discrimination ability (c-index 0.886) and calibration during internal validation and good clinical performance was observed through decision curve analysis. The external validation of CPCC-RC, an existing model, demonstrated that models based on TRUS-guided biopsy may underestimate the risk of HGPC in patients who underwent TTPB. CONCLUSION: We established a prediction model which showed good discrimination ability and calibration in predicting the detection of HGPC by initial TTPB. This model can be used to aid clinical decision making for Chinese patients and other Asian populations with similar genomic backgrounds, after external validations are conducted to further confirm its clinical applicability.

Tumor characteristics, treatments, and survival outcomes in prostate cancer patients with a PSA level < 4 ng/ml: a population-based study.

BACKGROUND: To examine the tumor characteristics, treatments and survival outcomes of prostate cancer (PCa) patients with a prostate-specific antigen (PSA) level < 4 ng/ml. METHODS: Of 205,913 men with primary prostate adenocarcinoma in the Surveillance, Epidemiology and End Results (SEER) database (2010 to 2015), 24,054 (11.68%) patients were diagnosed with a PSA level < 4 ng/ml. Comparisons of categorical variables among different groups were performed by using the Chi square test. Multivariate Cox regression analysis was adjusted for age, ethnicity, marital status, insurance status, TNM stage, Gleason grade, treatment and survival. Kaplan-Meier survival curves were constructed for overall mortality and tested by the log-rank test. RESULTS: PCa patients with a PSA level < 4 ng/ml generally had more favorable tumor characteristics: younger, lower T stage, lower Gleason grade and lower lymph node metastasis rate. However, there were more patients in stage M1 in the group of PSA level < 4 ng/ml than that in the groups of PSA level of 4-10 ng/ml, 10-20 ng/ml and > 20 ng/ml. The multivariate Cox regression model revealed that overall mortality was associated with age, marital status, race, Gleason grade, M stage and treatment approach. CONCLUSIONS: In conclusion, PCa patients with a PSA level < 4 ng/ml have more favorable tumor characteristics at diagnosis and receive more benefit from active treatment. However, those patients with advanced TNM stage and high Gleason grade should be paid more attention in clinical application.

The transverse and vertical distribution of prostate cancer in biopsy and radical prostatectomy specimens.

BACKGROUND: Prostate biopsy is the most common method for the diagnosis of prostate cancer and the basis for further treatment. Confirmation using radical prostatectomy specimens is the most reliable method for verifying the accuracy of template-guided transperineal prostate biopsy. The study aimed to reveal the spatial distribution of prostate cancer in template-guided transperineal saturation biopsy and radical prostatectomy specimens. METHODS: Between December 2012 to December 2016, 171 patients were diagnosed with prostate cancer via template-guided transperineal prostate biopsy and subsequently underwent laparoscopic radical prostatectomy. The spatial distributions of prostate cancer were analyzed and the consistency of the tumor distribution between biopsy and radical prostatectomy specimens were compared. RESULTS: The positive rate of biopsy in the apex region was significantly higher than that of the other biopsy regions (43% vs 28%, P < 0.01). In radical prostatectomy specimens, the positive rate was highest at the region 0.9-1.3 cm above the apex, and it had a tendency to decrease towards the base. There was a significant difference in the positive rate between the cephalic and caudal half of the prostate (68% vs 99%, P < 0.01). There were no significant differences between the anterior and posterior zones for either biopsy or radical prostatectomy specimens. CONCLUSION: The tumor spatial distribution generated by template-guided transperineal prostate biopsy was consistent with that of radical prostatectomy specimens in general. The positive rate was consistent between anterior and posterior zones. The caudal half of the prostate, especially the vicinity of the apex, was the frequently occurred site of the tumor.

Comparison of lesions detected and undetected by template-guided transperineal saturation prostate biopsy.

OBJECTIVES: To compare the characteristics of lesions detected or undetected by template-guided transperineal saturation prostate biopsy and to evaluate the potential impact of undetected lesions. MATERIALS AND METHODS: We evaluated the characteristics of lesions in radical prostatectomy (RP) specimens, compared the differences between lesions detected and undetected by systematic transperineal ultrasonography-guided 11-region biopsy with regard to tumour volume, Gleason score, surgical margin, spatial location and clinical significance, and assessed the potential impact of undetected clinically significant lesions. RESULTS: The median number of biopsy cores was 24. Sixty-four percent of the clinically significant lesions (170/264) were detected. There were significant differences between the detected and undetected lesions in tumour volume, Gleason score and clinical significance. Inconsistencies found in lesion position between biopsy and RP specimens in the anterior and posterior zones and the left and right sides was 3.4% (7/203) and 5.4% (11/203), respectively. Of the 129 patients, 13 (10.1%) were found to have undetected clinically significant lesions in the biopsy lying on the same side but in a different zone from the detected clinically significant lesions, whereas 23 patients (17.8%) had undetected clinically significant lesions in the biopsy lying on the opposite side from the detected clinically significant lesions. CONCLUSIONS: Template-guided transperineal saturation prostate biopsy detected approximately two-thirds of clinically significant lesions. Most of the undetected lesions were those with small tumour volume. Approximately 20-30% of patients had clinically significant undetected lesions in a different lobe or different quadrant from the detected lesions in the biopsy.

Transperineal template-guided prostate biopsy: 10 years of experience.

OBJECTIVE: To assess the efficacy and safety of transperineal template-guided prostate biopsy. MATERIALS AND METHODS: From December 2003 to December 2013, a total of 3 007 patients (30-91 years old, mean age 69.1) who met the inclusion criteria underwent 11-region transrectal ultrasound-guided transperineal template prostate biopsy. The inclusion criteria included a prostate-specific antigen (PSA) level of 4.0 ng/mL or greater and abnormal prostate gland findings on digital rectal examination, ultrasound, CT or MRI. The median PSA level was 11.0 ng/mL (range 0.2-100 ng/mL). The prostate cancer detection rate and prostate biopsy adverse effects, as well as prostate cancer spatial distribution were analyzed. RESULTS: A mean of 19.3 cores (range 11-44) were obtained for each biopsy, and more cores were obtained in larger prostates than in smaller ones. One to four cores were collected from each region. Prostate cancer was detected in 1 067 of the 3 007 patients (35.5%). The prostate cancer detection rates in groups with PSA levels of 0-4.0 ng/mL, 4.1-10.0 ng/mL, 10.1-20.0 ng/mL, 20.1-50.0 ng/mL, and 50.1-100.0 ng/mL were 15.3% (27/176), 21.0% (248/1 179), 32.6% (318/975), 56.0% (232/414), and 92.0% (241/262), respectively. The mean positives for cancer in regions 1-10 and region 11 (the apical region) were 46.7% vs 52.0% (P = 0.014). Regarding adverse effects, 47.0% of the patients reported hematuria, 6.1% developed hemospermia, 1.9% required short-term catheterization after biopsy because of acute urinary retention, and 0.03% (one patient) developed urosepsis. CONCLUSIONS: Transrectal ultrasound-guided transperineal template prostate biopsy is safe and accurate. The current study suggests that prostate carcinoma foci are more frequently localized in the apical region.

Outcomes of T3a Prostate Cancer with Unfavorable Prognostic Factors Treated with Brachytherapy Combined with External Radiotherapy and Hormone Therapy.

OBJECTIVE: To evaluate the outcomes of T3a prostate cancer with unfavorable prognostic factors treated with permanent interstitial brachytherapy combined with external radiotherapy and hormone therapy. METHODS: From January 2003 to December 2008, 38 patients classified as T3a prostate cancer with unfavorable prognostic factors were treated with trimodality therapy (brachytherapy + external radiotherapy + hormone therapy). The prescription dose of brachytherapy and external radiotherapy were 110 Gy and 45 Gy, respectively. The duration of hormone therapy was 2-3 years. The endpoints of this study included biochemical failure-free survival (BFFS), distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS). Survival curves were calculated using the Kaplan-Meier method. The Log-rank test was used to identify the prognostic predictors for univariate analysis. RESULTS: The median follow-up was 71 months. The serum pre-treatment prostate-specific antigen (PSA) level ranged from 10.0 to 99.8 ng/ml (mean 56.3 ng/ml), the Gleason score ranged from 5 to 9 (median 8), and the percentage of positive biopsy cores ranged from 10% to 100% (mean 65%). The 5-year BFFS, DMFS, CSS, and OS rates were 44%, 69%, 82%, and 76%, respectively. All biochemical failures occurred within 40 months. The percentage of positive biopsy cores was significantly correlated with BFFS, DMFS, and OS (all P=0.000), and the Gleason score with DMFS (P=0.000) and OS (P=0.001). CONCLUSIONS: T3a prostate cancer with unfavorable prognostic factors presents not so optimistic outcome. Hormone therapy should be applied to prolong the biochemical progression-free or metastasis-free survival. The percentage of positive biopsy cores and the Gleason score are significant prognostic factors.

[Clinical analysis of transperineal prostate biopsy in patients age ≤ 50 years].

OBJECTIVE: To assess the clinical features of transperineal prostate biopsy in patients age ≤50 years. METHODS: The clinical data of 124 patients ≤ 50 years old were retrieved retrospectively in Peking Union Medical College Hospital between January 2005 and September 2014. The age of patients were 14 to 50 years (mean age 43.6 years), and their prostatic specific antigen(PSA) levels were fluctuated in a range of 0.01 to 579.00 µg/L (mean 15.5 µg/L). Twenty patients were abnormal in digital rectal examination (DRE). All the patients were underwent transperineal prostate biopsy using an 11-region template. RESULTS: Prostate cancer was detected in 14 of 124 patients (11.3%). The prostate cancer detection rates in groups with PSA 0-4.0, >4.0-10.0, >10.0-20.0, >20.0-50.0, and >50.0 µg/L were 0, 6.2% (4/65), 13.3% (4/30), 1/5, and 5/5, respectively. Non-adenocarcinoma prostate malignancy (NAPM) was detected in 7 of 124 patients (5.6%), and their PSA levels were fluctuated in a range of 0 to 4.0 µg/L. Four patients were abnormal in DRE and 5 patients were abnormal in radiological examination. CONCLUSION: The positive rate of transperineal prostate biopsy in patients age≤50 years is low, and rigorous screening before prostate biopsy is necessary. The men with DRE or radiological abnormalities but normal PSA should be wary of NAPM.

[Analysis of permanent brachytherapy combined with maximal androgen blockade in local intermediated-risk prostate cancer].

OBJECTIVE: To evaluate the outcomes of permanent brachytherapy combined with maximal androgen blockade (MAB) in local intermediated-risk prostate cancer. METHODS: From December 2003 to December 2009, 307 patients of local prostate cancer were treated with brachytherapy, 98 cases of intermediated-risk were followed-up for 5 years and data were recorded, aged from 58 to 84 years, average 74 years. Serum PSA was 0.4-19.0 µg/L, average 11.2 µg/L, clinical TNM stage was T1cN0M0-T2bN0M0. Gleason score 4-7, 6.7 in average. Prostate volume ranged from 14 to 65 ml, average 32.1 ml. All the 98 patients underwent permanent brachytherapy combined with MAB. Biochemical recurrence rate, biochemical-free survival, tumor-specific survival, overall survival, salvage therapy and complications were analyzed. RESULTS: Followed up for 5 years, 19 cases had biochemical recurrence, median recurrence period: 36 months. One patient died of prostate cancer 45 months after brachytherapy of all 7 patients died in 5 years. Five-years biochemical-free recurrence rate: 80.6%, overall survival: 92.9%, tumor-specific survival: 98.9%, biochemical-free survival: 79.3%. Low-urinary tract and rectal irritation symptoms occurred in 75 cases(76.5%). Urinary retention occurred in 7 cases (7.1%) with catheterization duration less than 1 week, no surgical operation were performed. Seeds immigration to lung in 2 cases. No serious complications occurred. CONCLUSION: In local intermediated-risk prostate cancer patients, permanent brachytherapy combined with short-term MAB can be an effective treatment with few complications.

[Outcomes and predictors of T3a prostate cancer treated by permanent interstitial brachytherapy combined with external radiotherapy and hormone therapy].

OBJECTIVE: To evaluate the outcomes of T3a prostate cancer treated by permanent interstitial brachytherapy combined with external radiotherapy and hormone therapy, and analyse the influence of preoperative factors on prognosis. METHODS: From January 2003 to December 2008, 38 pactients with T3a prostate cancer aged from 48 to 81 years (mean: 71 years) were enrolled, with serum prostate specific antigen (PSA) levels ranged from 10.000 to 99.800 µg/L (mean: 56.300 µg/L), Gleason score from 5 to 9 (mean: 7.6) and percentage of positive biopsy cores from 10.0% to 100% (mean: 65.3%). All patients were treated by permanent interstitial brachytherapy combined with external radiotherapy and hormone therapy. Survival curves were calculated using the Kaplan-Meier method. The predictive factors including patient's age, prostate volume, serum pre-treatment PSA, Gleason score and percentage of positive biopsy cores were used for univariate analysis on biochemical failure-free, distant metastasis-free and overall survival. RESULTS: The mean follow-up was 69 months (range: 9-109 months).Nineteen patients experienced biochemical failure. The average biochemical failure time was 13.4 months (range: 1-40 months). There were 13 patients developed as distant metastatic prostate cancer since average 19.7 months (range: 1-70 months) after brachytherapy. Of all patients, 9 died of prostate cancer recurrence, while 6 passed away because of other reasons, with an average of 52.2 months (range: 9.0- 98.5 months). The 5-year biochemical failure-free survival (BFFS), distant metastasis free survival (DMFS), cancer specific survival (CSS) and overall survival (OS) rate were 44.1%, 68.6%, 82.4 and 75.8%, respectively. Twenty-nine patients experienced grade 1-2 gastrointestinal toxicity and 18 patients experienced grade 1-2 genitourinary toxicity. In univariate analysis, the percentage of positive biopsy cores was significantly correlated with BFFS (χ(2) = 17.240, P = 0.000), DMFS (χ(2) = 18.641, P = 0.000) and OS (χ(2) = 8.970, P = 0.003); the Gleason score was significantly correlated with DMFS (χ(2) = 12.484, P = 0.000) and OS (χ(2) = 6.575, P = 0.010); and patient's age was significantly correlated with OS (χ(2) = 5.179, P = 0.023). CONCLUSIONS: Permanent interstitial brachytherapy combined with external radiotherapy and hormone therapy is alternative for T3a prostate cancer. The percentage of positive biopsy cores is correlated with BFFS, DMFS and OS.

[Retracted] Tetramethylpyrazine inhibits prostate cancer progression by downregulation of forkhead box M1.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell invasion assay data shown in Fig. 3B on p. 839 were strikingly similar to data that had already appeared in another article written by different authors at different research institutes [Mao Y, Zhang L, Yuan L, Yan M and He Y: MiR­218 suppresses cell progression by targeting APC in cervical cancer. Int J Clin Exp Pathol: 10, 2259­2269, 2017]. 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: 837­842, 2017; DOI: 10.3892/or.2017.5768].

Comparison of the efficacy and safety profiles of generic and branded leuprorelin acetate microspheres in patients with prostate cancer.

Leuprorelin acetate microspheres, a common gonadotropin-releasing hormone agonist, have certain clinical benefits for prostate cancer (PCa). The present study aimed to compare the efficacy and safety of generic and branded leuprorelin acetate microspheres in patients with PCa. The present retrospective, observational study included 116 patients with PCa who received generic (Boennuokang®; Beijing Biote Pharmaceutical Co., Ltd.) or branded (Enantone®; Takeda Pharmaceutical Company, Ltd.) leuprorelin acetate microspheres via injection (commonly 3.75 mg once every 4 weeks), defined as the test (n=64) and reference (n=52) groups, respectively. The present study showed that testosterone levels at month (M) 3 (P<0.001), M6 (P=0.012) and M12 (P<0.001) were decreased in the test group compared with the reference group. However, prostate-specific antigen (PSA) levels at baseline, M1, M3, M6 and M12 were not significantly different between the test and reference groups (all P>0.05). The median (interquartile range) testosterone and PSA levels at M12 were 15.50 ng/dl (10.00-31.25 ng/dl) and 0.01 ng/ml (0.01-0.10 ng/ml), respectively, in the test group and 28.00 ng/dl (22.00-37.00 ng/dl) and 0.02 ng/ml (0.01-0.16 ng/ml), respectively, in the reference group. No significant differences were observed in the M1-baseline, M3-baseline, M6-baseline and M12-baseline changes of testosterone or PSA levels between the two groups (all P>0.050). Additionally, the incidence of all adverse events was not significantly different between the two groups (all P>0.050). Overall, Boennuokang® leuprorelin acetate microspheres exhibited a similar efficacy for suppression of testosterone and PSA levels with a comparable safety profile compared with Enantone® leuprorelin acetate microspheres in patients with PCa.

Association between body mass index and sex hormones among men: Evidence from cross-sectional and Mendelian randomization studies.

PURPOSE: This study aims to investigate the association between Body Mass Index (BMI) and sex hormone levels utilizing a cross-sectional study design alongside Mendelian randomization (MR) analysis. MATERIALS AND METHODS: A cross-sectional study was performed based on National Health and Nutrition Examination Survey (NHANES) 2013-2016. Additionally, a two-sample MR analysis was performed, utilizing Single Nucleotide Polymorphisms (SNPs) associated with BMI identified in a genome-wide association study (GWAS) comprising 339224 individuals. Data on outcomes, including total testosterone (TT, 199569 samples), estradiol (E2, 17134 samples), and sex hormone binding globulin (SHBG, 185211 samples), were sourced from the United Kingdom Biobank (UKB). RESULTS: In cross-sectional analysis involving 4092 males, multivariable linear regression demonstrated that each unit increase in BMI was positively correlated with an elevated risk of testosterone deficiency (TD), increased E2 levels, and a reduced TT, SHBG, free androgen index and TT/E2. Subsequent quartile division of BMI revealed, through multivariable logistic regression, that higher BMI quartiles were associated with a greater TD risk, elevated E2 levels, and reduced TT, SHBG, and TT/E2 levels compared to quartile 1 (P for trend <0.001). In the MR analysis, a causal effect was established, with each unit increase in BMI being associated with decreased TT (ß = -0.17; 95 % CI -0.24 to -0.09) and SHBG (ß = -0.13; 95 % CI -0.21 to -0.05) levels. CONCLUSIONS: Our findings unveil a causal link between BMI and reduced TT and SHBG levels in males.