You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III (PD35)1 May 2024PD35-05 M2-LIKE MACROPHAGE PROMOTES PROSTATE CANCER METASTASIS BY HORIZONTAL TRANSFER OF TXNDC5 MRNA VIA EXTRACELLULAR VESICLES Cong Hu, Tianyang Wu, Xinxing Du, Zehong Peng, Qi Chen, Yinjie Zhu, Baijun Dong, Jiahua Pan, Liang Dong, and Wei Xue Cong HuCong Hu , Tianyang WuTianyang Wu , Xinxing DuXinxing Du , Zehong PengZehong Peng , Qi ChenQi Chen , Yinjie ZhuYinjie Zhu , Baijun DongBaijun Dong , Jiahua PanJiahua Pan , Liang DongLiang Dong , and Wei XueWei Xue View All Author Informationhttps://doi.org/10.1097/01.JU.0001009396.21455.74.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The incidence of prostate cancer (PCa) is on the rise worldwide, and metastatic PCa remains incurable. Tumor-associated macrophages in PCa tend to be M2 phenotype, which promote cancer metastasis, but the mechanism is not clear. Whether extracellular vesicles (EVs), as a means of intercellular communication, can mediate the above process needs to be further elucidated. METHODS: We explored the infiltration of M2-like macrophage in metastatic and non-metastatic PCa primary foci by single-cell sequencing, which was verified by immunohistochemistry and immunofluorescence in patient samples. EVs were separated from M2-like macrophages polarized from THP-1cell line, with differential ultracentrifugation. M2-derived EVs were co-incubated with PCa cell lines Du145 and PC3, and changes in invasion and migration ability were observed by Transwell and wound-healing assay. Differential genes that were co-altered were identified by RNA sequencing of the EVs-treated cells. Overexpression and knockdown of the differential gene were carried out to observe if they could change the metastatic ability of PCa cell. The above cell lines were injected through the tail vein of mice to observe systemic metastasis. GFP-tagged differential gene in EVs was applied to see if they can be delivered directly to target cells via EVs and translated into functional proteins to promote PCa metastasis. RESULTS: In our own patient cohort, single-cell sequencing demonstrated more M2-like macrophages infiltration of primary foci in metastatic PCa compared to non-metastatic PCa. Immunohistochemistry and immunofluorescence confirmed these results. Wound-healing assay and Transwell demonstrated enhanced migration and invasion of M2 EVs-treated DU145 and PC3. The RNA sequencing data of treated Du145 and PC3 revealed a common differential gene, TXNDC5. Overexpression and knocked-down of TXNDC5 in DU145 and PC3 verified its regulation of migration and invasion in vivo and in vitro. The presence of TXNDC5 gene in M2-derived EVs was further verified by qRT-PCR, and the fusion gene fused with GFP was found to be successfully translated in target cells with confocal microscopy and flow cytometry. CONCLUSIONS: Our study successfully demonstrated that TXNDC5 mRNA in M2-derived EVs is able to regulate PCa migration and invasion through horizontal delivery. Source of Funding: The National Natural Science Foundation of China (82103485) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e726 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Cong Hu More articles by this author Tianyang Wu More articles by this author Xinxing Du More articles by this author Zehong Peng More articles by this author Qi Chen More articles by this author Yinjie Zhu More articles by this author Baijun Dong More articles by this author Jiahua Pan More articles by this author Liang Dong More articles by this author Wei Xue More articles by this author Expand All Advertisement PDF downloadLoading ...

Background: Hyperfibrinogen is thought to be associated with a higher risk of invasion and metastasis, as well as a worse outcome for multiple types of cancer. However, the prognostic significance of plasma fibrinogen has not been investigated in prostate cancer with hormonal therapy. The objective of this study was to evaluate its roles in prostate cancer patients treated with androgen deprivation therapy (ADT). Methods: A total of 290 patients who underwent ADT as first-line therapy for prostate cancer were retrospectively analyzed. The fibrinogen level was measured at the time of diagnosis. Patients were categorized using a cutoff point of 3.225 g l −1 according to a calculation by the receiver operating curve analysis. Correlations between the fibrinogen and clinical characteristics were analyzed. Meanwhile, univariable and multivariable cox regression analyses were performed to determine the associations of fibrinogen with progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). Prognostic accuracy was evaluated with the Harrell concordance index. Results: Compared with patients with a lower fibrinogen level (<3.225 g l −1 ), patients with a higher fibrinogen level were more likely to have higher PSA, Gleason score, risk stratification and incidence of metastasis ( P <0.05). Multivariable analyses identified hyperfibrinogen as an independent prognostic factor for PFS (hazard ratio (HR)=2.000, P <0.001), CSS (HR=2.209, P =0.006) and OS (HR=1.965, P =0.009). The final models built by the addition of fibrinogen improved predictive accuracy (c-index: 0.750, 0.799 and 0.767) for PFS, CSS and OS compared with the clinicopathological base models (c-index: 0.730, 0.778 and 0.746), which included Gleason score and metastasis. Conclusions: The pretreatment plasma fibrinogen level was associated with tumor progression and might have a significant role in the prognosis of the prostate cancer patients treated with ADT. Thus, we recommend adding fibrinogen to traditional prognostic model, which may improve its predictive accuracy.

Objective To establish a reliable animal mode of ureteral injury and to screen the sensitive markers of fibrotic process after ureteral injury. Methods The bipolar electrocautery was applied to establish the animal model of ureteral injury in adult male New Zealand rabbits. The stricture part of the experimental ureter and contralateral normal ureter were harvested for macroscopic and pathologic examination by hematoxylin-eosin (H-E) staining. The expression of endothelium growth factor (EGF), transforming growth factor β (TGF-β), keratinocyte growth factor (KGF), collagen Ⅰ (Col Ⅰ) a1, Col Ⅰa2, Col Ⅲ and fibronectin (FN) in the impaired ureter and the contralateral normal ureter was quantified by reverse transcription polymerase chain reaction (RT-PCR) technique to search for the sensitive biomarkers of ureteral fibrosis. Results The animal model of ureteral injury was established successfully. The levels of EGF, TGF-β, FN, Col Ⅰa1 and Col Ⅰa2 in the stricture ureter were significantly higher than those in the contralateral normal ureter (P<0.05,P<0.01). Conclusion Ureteral injury animal model complicating ureteral stenosis can be established by bipolar electrocautery. EGF, TGF-β, Col Ⅰa1, Col Ⅰa2 and FN may play important roles in the ureteral fibrosis and scarring after ureteral injury.

Objective To evaluate the safety and efficacy of liver dissection technique combined with liver transplant incision on very huge tumor in upper pole of right kidney and tumor thrombus in the inferior vena cava. Methods From May 2007 to July 2011, right radical nephrectomy was carried out in 8 patients with liver dissection technique. The average age of the patients was (56.8±17.6) years (range, 32-83 years). The average diameter of tumor was (11.4±2.5) cm (range, [9.5-15] cm). Mayo Clinic five taxonomy was applied for tumor thrombus in the vena cava after MRI assessment. Three patients presented with renal hilum and retroperitoneal lymph node metastasis, 2 with grade 0 tumor thrombus, 2 with grade II tumor thrombus and 1 with grade III tumor thrombus. The piggyback liver transplantation was used to dissect the liver, and Pringle maneuver was tried to get a clearer operative field by briefly blocking the hepatic blood flow. After radical nephrectomy and thrombectomy, the inferior vena cava was reconstructed. All patients were sent to intensive care unit (ICU) postoperatively and stayed there for one day. Liver and kidney function were measured. Results The total thrombectomy and reconstruction of the inferior vena cava were successfully carried out in 3 patients with tumor thrombus. The range of tumor thrombus was correlated to MRI results. The average blood loss was (387.5±299.7) mL (range, [200-900] mL). Intraoperative blood loss was 300, 450 and 900 mL in the patients with grade 0, Ⅱ and Ⅲ tumor thrombus, respectively. The average operative time was (210.1±67.0) min (range, [137-309] min). Mean operative time was 212, 263.5 and 309 min in the patients with grade I, II and III tumor thrombus, respectively. No patients had severe complications during and after surgery. The levels of serum creatinine, alanine transaminase and aspartate transaminase were (99.3±8.7) μmol/L (86-113 μmol/L), (29.3±5.1) U/L (22-35 U/L) and (24.1±8.1) U/L (14-38 U/L), respectively. No patients presented with liver dysfunction related to Pringle maneuver. Conclusion The right superior vena cava-diaphragmatic angle, tumor collateral vessels, inferior vena cava, subdiaphragmatic blood vessels and right adrenal gland can be easily revealed by liver ligament dissection and liver mobilization. This technique can be applied in the huge tumor of right kidney with inferior vena cava Ⅰ—Ⅲ grade tumor thrombus. Transabdominal approach may not only reduce the risk of anesthesia and surgical trauma, but also avoid the thoracic drainage after surgery, which offers favorable conditions for postoperative care and early activities.

Objective To study the natural history of renal cell carcinomas associated with von Hippel-Lindau disease (VHL). Methods An active surveillance strategy was carried out on 11 VHL cases(5 males and 6 females with average age of 45 years)with 32 renal masses. The mean maximum diameter of these masses at initial diagnosis was 2. 5 cm ranging from 0. 5 to 6.2 cm. Clinical materials, radiographic, and pathologic records were reviewed to determine tumor growth rate, subsequent interventions and outcome of follow-up. Results During a median follow-up of 70 months (range 32 to 258 months), bilateral solid renal tumors developed in 6 patients;13 surgical interventions were performed in 8 cases;tumor local recurrence occurred in 4 cases;3 cases died (2 of metastasis diseases and 1 of an unrelated disease) ;8 cases survived with 1 case taking regular hemodialysis.The median follow-up duration for 32 renal masses was 51 months (range 19 to 106 months). The mean tumor growth rate observed were 0. 55 cm/year (range 0. 04 to 1.75 em/year). Three tumors grew faster (1.13-1.75 cm/year), and the other 29 tumors grew slower (0. 17-0.88 cm/year).Among the 3 tumors, 1 was found to be grade Ⅱ at pathologic examination and another developed metastasis. Progression to metastatic disease was found in 2 patients. At the last follow-up, 27 (84 %)tumors were larger than 3 cm and no metastasis disease developed among tumors less than 4 cm.Conclusions The majority of enhanced renal masses with VHL disease may still be indolent and do not metastasize during long period of follow-up even in tumors larger than 3 cm. Active surveillance appears to be a reasonable option for VHL patients with enhanced renal masses less than 4 cm.

Objective To evaluate the clinical efficacy and safety of anterograde flexible ureteroscopic lithotripsy in the management of ureterointestinal anastomotic calculus after Bricker procedure by a retrospective analysis of 11 cases. Methods From March 2006 to July 2009,11 patients with ureterointestinal anastomotic calculus after Bricker procedure were enrolled in this study. The average age of the patients was (62±9) years old. The first clinic presentation was averagely (8.2±3.2) months after the Bricker procedure (5-16 months). There were 7 cases with left side calculi and 4 cases with right side ones. The urinary tract ultrasound and the multiplanar CT reconstruction were carried out to identify the obstructive portion of the ureter. Seven cases without complications underwent percutaneous nephrostomy and simultaneous anterograde flexible ureteroscopic lithotripsy. Simple nephrostomic drainage was carried out for 3 cases with obstructive upper urinary tract infection and a second time anterograde flexible ureteroscopic lithotripsy was done 3 weeks after the antibiotics, nearly the same as the patients with right unique kidney and acute renal failure due to the ureterointestinal anastomotic calculus. The 7F soft mono J ureteral stent was indwelled for 4 weeks. The intravenous antibiotics were administered during the first 2 days after the surgery. A kidney ureter and bladder X-Ray (KUB) or a CT scan was performed 4 weeks after the procedure to evaluate the clinical outcomes. Any residual calculus larger than 4 mm was taken as significant. Results The nephrostomic procedure was successful in all the cases. The upper urinary tract infection was well controlled in all the 3 cases and the serum creatinine decreased in the case with acute renal failure. The flexible ureteroscopic lithotripsy was carried out smoothly in all the 11 cases. The mean operative time was (40±9.3) min (25-55 mins). The nephrostomic catheter was removed 72 hours after the surgery. The mean hospital stay was (3.3±0.9) days. The average blood loss was less than 50ml. No residual calculus was found during the 4 weeks’ follow-up. The average follow-up was 19 months. One case had recurrent calculus 13 months after the first procedure, which was successfully managed by the flexible ureteroscopy again. Two cases had ureteral stricture at the lower ureter at 3 and 8 months after the first intervention. In these 2 cases, an exploration by the anterograde flexible ureteroscopy combined with the balloon dilation was done and an indwelling soft mono J stent was changed every 6 months. Conclusion The anterograde flexible ureteroscopic lithotripsy is safe and effective for ureterointestinal anastomotic calculus after Bricker procedure, with less complications, low recurrence rate, and a high calculus removing rate. Four week stenting of mono J ureteral stent after operation can help to prevent ureterointestinal anastomotic stricture.

Objective:To summarize the characteristics of MSCT of the upper urinary tract fungal bezoars and to evaluate the feasibility and clinical value of MSCT in the diagnosis and treatment of obstructing renal fungal ball. Methods: A retrospective study of 4 cases with upper urinary collecting system fungal bezoars complicating urinary tract obstruction from April 2007 to December 2009. 2 males and 2 females were enrolled in this study and in all the cases, the obstruction was unilateral. Case 1:female,37-year-old, came to the emergency room for high fever and pyonephrosis with a surgical history of percutaneous nephrostomic lithotomy in the right kidney 6 months ago. The patient had a medical history of dermatomyositis treated by corticosteroid. Case 2:Female, 42- year-old with DM, came to the clinic for right ureteropelvic junction obstruction and hydronephrosis. Case 3: Male, 57-year-old, came to the clinic for left ureteral stone and left hydronephrosis. Case 4:Male, 52-year-old, consult in the ER for anuria with right unique kidney. The MSCT without enhancement was realized in all the 4 cases. The GE Light Speed 16 CT was used in these cases with the following parameters: 120 kV, 280 mA, 1. 25 mm reconstruction slice, 1. 375: 1, window width 360 HU, window site 60 HU. Results:In all the 4 cases, MSCT showed that the infected kidney was enlarged with a hydronephrosis. The perinephretic fascia was thick and some high density lines could be found in the perinephretic fat tissue. Some high density mass could be recognized in the collecting system as well as the UPJ junction with a CT value of 180-235. There was no parenchymal necrosis or abscess found in the kidney. The PCN drainage and local irrigation of anti-fungal medication was realized in all the cases to control the severe infection and the fungal bezoars were extracted by the percutaneous access. The urine fungal culture was positive in all the cases. These were no systemic fungal infection or massive haemorrhage during the peri-operative phase. No medication-related kidney or liver impairment was found. Conclusions:The MSCT was widely available and almost suitable for all the cases except for the pregnant women. The CT value could help to make the right diagnosis of fungal bezoars, which makes the managements of such patients more correct, suitable and safe.

To evaluate the feasibility and the clinical outcome of the transurethral resection of prostate by plasmakinetic TUR system in the BPH patients with high surgical risk pretreated by short-term (3 months) subcutaneous administration of goserelin acetate.

To investigate the feasibility and the efficacy of endoscopic management of ureterointestinal anastomotic stricture of the STUDER neobladder by the flexible ureteroscope.

To study the pathological basis of the iatrogenic ureteric lesion complicating upper tract obstruction, to evaluate the efficacy of different surgical strategies in these cases.