To evaluate the diagnostic value of 68Ga-PSMA-11 PET-CT with multiparametric magnetic resonance imaging (mpMRI) for lymph node (LN) staging in patients with intermediate- to high-risk prostate cancer (PCa) undergoing radical prostatectomy (RP) with pelvic lymph node dissection (PLND). We retrospectively identified 42 consecutive patients with intermediate- to high-risk PCa according to D′Amico and without concomitant cancer. Preoperative 68Ga-PSMA-11 PET-CT, pelvic mpMRI and subsequent robot assisted laparoscopic RP with PLND were performed in all patients. Among 42 patients assessed, the preoperative PSA value, Gleason score, pT stage and intraprostatic PCa volume of patients with LN metastases were all significantly higher than those without metastases (P = 0.029, 0.028, 0.004, respectively). The average maximum standardized uptake value (SUV) of 68Ga-PSMA-11 PET-CT positive PCa of patients with or without LN metastases were 13.10 (range 6.12–51.75) and 7.22 (range 5.4–11.2), respectively (P < 0.001). 68Ga-PSMA-11 PET-CT and pelvic mpMRI had the ability of succeed on preoperative definite accurate diagnosis and accurate localization of primary PCa in all 42 patients. Fifteen patients (35.71%) had a pN1 stage. 51 positive LN were found. Both 68Ga-PSMA-11 PET-CT and pelvic mpMRI displayed brillient patient-based and region-based sensitivity, specificity, negative predictive value and positive predictive value. There was no statistical difference for the detection of LNMs according to the diameter of the LNMs between 68Ga-PSMA-11 PET-CT and mpMRI in this study. Both 68Ga-PSMA-11 PET-CT and mpMRI performed great value for LN staging in patients with intermediate- to high-risk PCa undergoing RP with PLND. However, despite excellent performance of 68Ga-PSMA-11 PET-CT, it cannot replace mpMRI that remains excellent for lymph node staging.
Background: Bladder cancer is the most common malignant tumor of the urinary system. Surgical resection and chemotherapy are the two mainstream treatments for bladder cancer. However, the outcomes are not satisfactory for patients with advanced bladder cancer. There is a need to further explore more effective targeted therapeutic strategies. Methods: Proteomics were performed to compare protein expression differences between human bladder cancer tissues and adjacent normal tissues. The function of GPD1 on bladder cancer cells were confirmed through in vivo and in vitro assays. Transcriptomics and metabolomics were performed to reveal the underlying mechanisms of GPD1. Virtual screening was used to identify allosteric activator of GPD1. Results: Here, we used proteomics to find that GPD1 expression was at low levels in bladder cancer tissues. Further investigation showed that GPD1 overexpression significantly promoted apoptosis in bladder cancer cells. Based on transcriptomics and metabolomics, GPD1 promotes Ca2+ influx and apoptosis of tumor cells via the lysoPC-PAFR-TRPV2 axis. Finally, we performed a virtual screening to obtain the GPD1 allosteric activator wedelolactone and demonstrated its ability to inhibit bladder tumor growth in vitro and in vivo. Conclusions: This study suggests that GPD1 may act as a novel tumor suppressor in bladder cancer. Pharmacological activation of GPD1 is a potential therapeutic approach for bladder cancer.
To compare the complications of traditional transrectal (TR) prostate biopsy and image fusion guided transperineal (TP) prostate biopsy in our center. Two hundred and fourty-two patients who underwent prostate biopsy from August 2014 to January 2015were reviewed. Among them, 144 patients underwent systematic 12-core transrectal ultrasonography (TRUS) guided prostate biopsy (TR approach) while 98 patients underwent free-hand transperineal targeted biopsy with TRUS and multi-parameter magnetic resonance imaging (mpMRI) fusion images (TP approach). The complications of the two groups were presented and a simple statistical analysis was performed to compare the two groups. The cohort of our study include242 patients, including 144 patients underwent TR biopsies while 98 patients underwentTP biopsies. There was no significant difference of major complications, including sepsis, bleeding and other complication requiring admissionbetween the two groups (P > 0.05). The incidence rate of infection and rectal bleeding in TR was much higher than TP (p < 0.05), but the incidence rate of perineal swelling in TP was much higher than TR (p < 0.05). There were no significant differences of minor complications including hematuria, lower urinary tract symptoms (LUTS), dysuria, and acuteurinary retention between the two groups (p > 0.05). The present study supports the safety of both techniques. Free-handTP targeted prostate biopsy with real-time fusion imaging of mpMRI and TR ultrasound is a good approach for prostate biopsy.
1 October 2020 in International Urology and Nephrology
The mechanisms underlying the effects of cancer-associated fibroblasts (CAFs) on cancer stemness and tumor progression in renal cell carcinoma (RCC) have not been elucidated yet. In the present study, we found that the enrichment of CAFs was positively associated with tumor progression and cancer stemness in RCC. Further investigation revealed that CAFs could enhance cancer stemness through delivering exosomes to RCC cells, and miR-181d-5p was identified as the critical exosomal miRNA in CAF-secreted exosomes by small RNA sequencing and subsequent screening assays. Mechanistically, exosomal miR-181d-5p transferred from CAFs to RCC cells directly suppressed the expression of ring finger protein 43 (RNF43) and activated Wnt/β-catenin signaling pathway, thus promoted cancer stemness and tumor progression. Overexpression of RNF43 strongly suppressed stemness properties and the effects could be reverted by miR-181d-5p. Overall, our findings revealed a crucial mechanism by which CAF-secreted exosomal miRNAs to enhance cancer stemness and thus promote RCC progression, suggesting a new avenue based on CAF-secreted miRNAs for more effective targeted therapies.