Nomogram for predicting the overall survival and cancer-specific survival of patients with intraductal carcinoma of the prostate.

PURPOSE: Intraductal carcinoma of the prostate (IDC-P) is a histological subtype that differs from conventional acinar adenocarcinoma in terms of its origin, appearance, and pathological features. For IDC-P, there is currently no recognized best course of action, and its prognosis is unclear. The goal of this study is to analyze independent prognostic factors in IDC-P patients and to develop and validate a nomogram to predict overall survival (OS) and cancer-specific survival (CSS). METHODS: Clinical data for IDC-P patients were collected from the Surveillance, Epidemiology, and End Results database. To identify the independent variables influencing prognosis, multivariate Cox regression analysis was performed. A nomogram model was created utilizing these variables after comparing the variations in OS and CSS among various subgroups using Kaplan‒Meier curves. Internal validation of the nomograms was verified using the bootstrap resampling method. RESULTS: The study included 280 IDC-P patients in total. Marital status, summary stage, grade, and the presence of lung metastases were significant factors impacting OS, and CSS was significantly influenced by marital status, summary stage, AJCC stage, the presence of lung metastases, the presence of bone metastases, and PSA according to univariate and multivariate Cox regression models (P < 0.05). Nomogram models were created to estimate OS and CSS using these parameters. The OS prediction model's C-index was 0.744, whereas the CSS prediction model's C-index was 0.831. CONCLUSION: We developed and verified nomogram models for the prediction of 1-, 3-, and 5-year OS and CSS in patients with IDC-P. These nomograms serve as a resource for evaluating patient prognosis, therapy, and diagnosis, ultimately improving clinical decision-making accuracy.

Efficacy and Safety of 1470 nm Diode Laser Enucleation of the Prostate in Elderly Benign Prostatic Hyperplasia Patients.

Objective: The aim of this study was to evaluate efficacy and safety of 1470 nm diode laser enucleation of the prostate (DiLEP) and plasmakinetic resection of the prostate (PKRP) in elderly benign prostatic hyperplasia (BPH) patients with lower urinary tract symptoms. Methods: A total of 123 elderly patients with BPH were randomized to undergo either 1470 nm DiLEP or PKRP by means of a random number table from September 2020 to April 2022. The perioperative and postoperative data were studied during a 3- and 6-month follow-up. Results: The patients treated with 1470 nm DiLEP had significantly decreased operation time (74.6 ± 17.0 vs 98.8 ± 18.9 minutes, p < 0.001), hemoglobin loss (1.06 ± 0.49 vs 1.59 ± 0.60 g/dL, p < 0.001), bladder irrigation time (22.1 ± 8.1 vs 33.9 ± 10.0 hours, p < 0.001), catheter duration (3.2 ± 1.3 vs 5.8 ± 1.0 days, p < 0.001), and hospital stay (7.6 ± 1.4 vs 9.6 ± 1.3 days, p < 0.001) compared with the PKRP group. Besides, International Index of Erectile Function-5 score of 1470 nm DiLEP group at postoperative 3- and 6-month follow-up was significantly higher than PKRP group. No differences achieving statistical significance were identified in total prostate-specific antigen, maximum urinary flow rate, International Prostate Symptom Score, quality-of-life score, and the postvoid residual urine volume, transient incontinence, urethral stricture, bladder neck contracture, and retrograde ejaculation at 3- and 6-month follow-up. Conclusions: 1470 nm DiLEP is safer than PKRP, with a smaller effect on sexual function, and it is comparable with the efficacy of PKRP, thus making it more suitable for elderly BPH patients. Clinical Trial Registration number: S2021-463-01.

Adrenal Gland Metastasis of Breast Invasive Mucinous Carcinoma: A Rare Case Report and Review of Literature.

The adrenal gland is a frequent site for metastasis, and the majority of the metastatic lesions of the adrenal gland normally originate from lung cancer, colon cancer, renal cell carcinoma, and melanoma. However, adrenal gland metastasis from breast invasive mucinous carcinoma is extremely rare. This report described a rare case of right adrenal gland metastasis in a 48-year-old female, who was diagnosed with breast invasive mucinous carcinoma and underwent right modified radical mastectomy with axillary lymph node dissection 5 years previously. A mass located on the right adrenal gland was detected during a routine examination 2 months ago. The patient was asymptomatic and adrenal gland MRI revealed a mass in the right adrenal gland. Definitive preoperative diagnosis failed to be established. Right adrenal gland laparoscopic adrenalectomy was performed and the diagnosis of adrenal gland metastasis of breast carcinoma was confirmed by pathological and immunohistochemical examination, especially ER, PR, GATA3, and HER-2. The patient remained in good condition by the time of writing.

Extraperitoneal Laparoscopic Modified Y-V Plasty for the Treatment of Refractory Bladder Neck Contracture.

Bladder neck contracture (BNC) is a rare, late complication of transurethral resection of the prostate (TURP). Although the endoscopic procedure is the primary treatment for BNC, the recurrence rate remains high. Y-V plasty offers excellent surgical results for those individuals with refractory and recurrent BNC. Traditional open operations usually fail to provide satisfactory exposure to the operating field and lead to greater invasiveness. Interrupted sutures lead to prolonged operative time and increased anastomotic leakage. Laparoscopic modified Y-V plasty is performed through extraperitoneal access to the pelvis, which provides adequate exposure to the surgical view and avoids intra-abdominal injury. After incising the anterior bladder wall neck in a Y-shaped fashion, anastomosis is performed using two absorbable barbed sutures. The mucosa and submucosa layer of the bladder is closed to both sides with consecutive sutures in a V-shape before suturing serosa, and tunica muscularis are sutured to reinforce. The aforementioned procedures reduce leakage from the anastomosis and decrease operative time and patient trauma. Extraperitoneal laparoscopic modified Y-V plasty offers significant advantages over the open approach in terms of post-surgical recovery and invasiveness, making it a feasible and safe surgical option for patients with refractory BNC.

Establishing a Thermal Imaging Technology (IRT) Based System for Evaluating Rat Erectile Function.

INTRODUCTION: Measurement of intra-cavernous pressure (ICP) is an internationally recognized method to evaluate erectile function of animals, however, this process is invasive, destructive, and cannot be repeated, leading to a daunting challenge for monitoring the changes in erectile function throughout the whole treatment duration. AIM: To verify whether infrared ray thermography technology based system could be a good substitution of ICP for evaluating rat erectile function. METHODS: A novel thermal image-based method, infrared ray thermography technology (IRT) was employed to monitor erectile function in erectile dysfunction (ED) rats. To detect the sensitivity and specificity of this new technology, 4 ED rat models (Diabetic, nerve-injury, vascular-injury and aged ED models) were established and subjected to both ICP and IRT test. OUTCOMES: Statistical comparisons were done to test the effectiveness of this new way for detecting and dynamically monitoring erectile function. RESULTS: Based on the data curves obtained from ICP and IRT, the IRT showed a similar trend (including peak value, climbing speed) as that of ICP. IRT is considered as a precise way to monitor the real-time changes of erectile function in all ED rat models. The AUC of peak temperature detected by IRT in DMED, aged ED, vascular-injury ED, the nerve-injury ED and total ED rat models were 0.9811,0.9836,0.9893,0.9989 and 0.9882, respectively. Meanwhile, the AUC of temperature climbing rate were 0.6486,0.8357,0.9184,0.8675and 0.8168.Also,it is a non-invasive process of dynamically monitoring erectile function of a same rat at different time points (before and after drug intervention). The data showed that the real-time recovery by tadalafil was obtained by IRT methods even after treatment for only 2 weeks in the diabetic ED (DMED) rat model. CONCLUSION: A novel noninvasive method for monitoring erectile function in rat ED models was established, and can replace or supplement ICP test. Liu S, Zhao Z, Wang Z et al. Establishing a Thermal Imaging Technology (IRT) Based System for Evaluating Rat Erectile Function. Sex Med 2022;10:100475.

[RigiScan monitoring assists tadalafil medication in the treatment of penile ED].

OBJECTIVE: To investigate the application value of RigiScan monitoring in assisting tadalafil medication. METHODS: This self-control study included 89 ED patients (IIEF-5 < 21) treated in our hospital from August 2019 to July 2020. The patients underwent audiovisual sexual stimulation (AVSS), nocturnal penile tumescence and rigidity (NPTR) test, scoring on the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-Item Scale (GAD-7), blood routine test, blood biochemical analysis, and hormone secretion examination, which confirmed 21 cases of psychogenic, 28 cases of organic and 40 cases of mixed ED. We treated the patients with tadalafil at 5 mg/d for 30 days, followed by examination of their erectile function by IIEF-5 scoring and AVSS and comparison of their erectile function with the baseline. For some of the patients that responded poorly to tadalafil at 5 mg/d, we increased the dose to 20 mg and detected the efficacy by AVSS at 1 h after medication. For those with organic or mixed ED irreponsive to tadalafil at 20 mg, we performed screening for corpora cavernosal venous leakage (CCVL) by intracavernosal injectionof alprostadil and penile color Doppler duplex ultrasonography or used dynamic infusion cavernosometry and cavernosography (DICC) to confirm the diagnosis of CCVL. RESULTS: The effectiveness rates of 5 mg/d tadalafil on mild, moderate and severe ED were 85.4%, 53.1% and 43.8%, respectively, significantly higher on mild than on moderate and severe ED (P = 0.002), and its effectiveness rates on psychogenic, organic and mixed ED were 90.5%, 60.7% and 57.5%, respectively, remarkably higher on psychogenic than on organic and mixed ED (P = 0.026). For those with organic or mixed ED irresponsive to 5 mg/d tadalafil, the increased dose of 20 mg achieved an effectiveness rate of 64.3%. (P = 0.033). The results of DICC did not encourage tadalafil medication for the cases of organic or mixed ED with CCVL irresponsive to both 5 mg and 20 mg tadalafil. CONCLUSION: RigiScan monitoring plays a guiding role in tadalafil medication of ED and helps distinguish organic from psychogenic ED. Tadalafil at 5 mg/d produces a better effect on mild than on moderate and severe ED, and so does it on psychogenic than on organic and mixed ED. The dose of medication can be increased to 20 mg for organic and mixed ED irresponsive to 5 mg tadalafil, but tadalafil is not recommended for organic and mixed ED with CCVL irresponsive to both 5 mg and 20 mg tadalafil.

Overexpression of replication protein A3 is associated with unfavorable outcome in bladder urothelial carcinoma.

PURPOSE: The replication protein A3 (RPA3) is a subunit of the RPA protein complex, which plays an essential role in multiple processes of DNA metabolism. However, the involvement of RPA3 bladder urothelial carcinoma (UC) prognosis has not yet been elucidated. The aim of our study is to investigate the prognostic role of RPA3 expression in patients with bladder UC. MATERIALS AND METHODS: Bladder UC tissue specimens from 155 consecutively treated patients who underwent surgery between 2013 and 2018 were evaluated. The RPA3 expression was determined by immunohistochemistry, Western blot, and correlated with clinicopathological parameters. The prognostic significance of RPA3 expression was explored using the univariate and multivariate survival analysis of 155 patients who were followed. RESULTS: A total of 155 tissue specimens "of patients" who were regularly followed with the mean 39.6 months (from 4 to 71 months). The expression of RPA3 was significantly associated with tumor grade (P = 0.031) and stage (P = 0.021), as well as tumor size (P = 0.034). In univariate analysis, RPA3 overexpression showed an unfavorable influence on recurrence-free survival with statistical significance (P < 0.01). TNM stage and grade also showed strong statistical relation with adverse recurrence-free survival (P < 0.01, P = 0.030). Multivariate analysis revealed that grade, stage, and RPA3 reactivity (P = 0.025, P < 0.01, P = 0.016) were identified as independent prognostic factors for recurrence-free survival in patients with bladder UC. CONCLUSIONS: These results of this study proved that elevated expression of RPA3 was associated with worse clinical outcome in bladder UC patients. This finding suggested that RPA3 served as a potential prognostic biomarker, which could be useful to predict cancer evolution and may represent a novel therapeutic target for the intervention of bladder UC patients.

Probucol enhances the therapeutic efficiency of mesenchymal stem cells in the treatment of erectile dysfunction in diabetic rats by prolonging their survival time via Nrf2 pathway.

BACKGROUND: Intracavernous injection of mesenchymal stem cells (MSCs) is a promising method for diabetic mellitus-induced erectile dysfunction (DMED), but short survival time of MSCs in cavernous is a fatal defect for therapy. This study investigated therapeutic efficiency and potential mechanism of probucol combined with MSCs. METHODS: In vivo study, a total of forty-eight 10-week-old male Sprague-Dawley (SD) rats were used. Twelve rats received intraperitoneal injection of PBS as the sham group; the rest received intraperitoneal injection of 60 mg/kg streptozotocin to establish DM models. DM rats were randomly divided into three groups: received intracavernosal (IC) injection of either PBS (DM group), MSCs (M group), or administrated probucol after intracavernosal injection of MSCs (P + M group). Erectile function was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure measurement. After euthanasia, penile tissue was investigated for histologic examination and Western blotting. In in vitro experiment, H2O2 was used to create oxidative stress environment to detect changes in cell viability. CCK8 was used to measure cell viability of MSCs treated with or without probucol. Intracellular ROS changes were detected by flow cytometry. Autophagy and apoptosis were detected by Western blotting and confocal microscopy. RESULTS: Recovery of erectile function was observed in the P + M group. The combination therapy decreased fibrosis and increased endothelial function compared with MSC therapy alone. Western blotting results confirmed the increased expression of Nrf2 and HO-1 in cavernous body. H2O2 induced high oxidative stress and reduced cell viability in vitro, which was gradually reversed with increased concentration of probucol. H2O2 reduced Nrf2 expression, which was reversed by probucol's intervention. Furthermore, the expression of Bax, Caspase3, and Cleaved-Caspase3 decreased, and the expression of Bcl-2 increased in a dose-dependent manner because of probucol's intervention. In addition, Beclin1 and LC3II both increased in a dose-dependent manner. Meanwhile, the expression of P62 decreased. In the study of autophagy flux, we found probucol did not block it. CONCLUSION: Probucol enhanced therapeutic efficiency of MSCs in DMED by prolonging their survival time, which mediated through improving the transplanted microenvironment of MSCs, increasing self-antioxidant ability of MSCs, strengthening protective autophagy, and inhibiting apoptosis of MSCs via Nrf2 pathway. Schematic model showing combined probucol and MSCs to improve DMED. Probucol increases self-antioxidant ability of MSCs, strengthening protective autophagy and inhibiting apoptosis via Nrf2/HO-1 and Nrf2/autophagy pathways.

MK2206 Enhances Cisplatin-Induced Cytotoxicity and Apoptosis in Testicular Cancer Through Akt Signaling Pathway Inhibition.

OBJECTIVE: To improve conventional chemotherapeutic efficacy, it is significant to identify novel molecular markers for chemosensitivity as well as possible molecules accelerating cell-killing mechanisms. In this study, we attempted to elucidate how MK2206, an allosteric Akt inhibitor, enhances the cisplatin (CDDP)-induced cytotoxicity and apoptosis in testicular cancer. MATERIALS AND METHODS: We checked three testicular cancer cell lines for the expression of phospho(p)-Akt and its downstream molecules targets by Western blot. The potential antitumor effects were analyzed by MTT assay in vitro and by subcutaneous xenograft models in vivo. The cell invasion was analyzed by transwell invasion assay, and the activities of Akt signaling pathway and expression of apoptosis-related proteins were measured by Western blot. RESULTS: Our results indicated that there was overactivation of p-Akt and its downstream molecules in testicular cancer cell lines compared with normal testis epithelium cells. MK2206 (600 nM) inhibited cell invasion in TCAM-2 and P19 cell lines and significantly increased the susceptibility of testicular cancer to CDDP. Combined with CDDP, MK2206 potentiated CDDP-induced cytotoxicity and apoptosis, with repressed expression of p-Akt and its downstream targets. The subcutaneous xenograft models also showed that a combined CDDP/MK2206 therapy completely suppressed tumor growth without any side effects. CONCLUSION: These results suggested that the concomitant use of MK2206 could enhance the CDDP-induced cytotoxicity and apoptosis in testicular cancer with the suppressed expression of Akt pathway.

Is targeted magnetic resonance imaging/transrectal ultrasound fusion prostate biopsy enough for the detection of prostate cancer in patients with PI-RADS ≥3: Results of a prospective, randomized clinical trial.

OBJECTIVE: To evaluate targeted magnetic resonance imaging/transrectal ultrasound (MRI/TRUS) fusion prostate biopsy versus systematic prostate biopsy and the two approaches combined for the detection of prostate cancer (PCa) and clinically significant PCa (csPCa) in our center. PATIENTS AND METHODS: From September 2018 to June 2020, a total of 161 patients with PI-RADS ≥3 were enrolled in this study. They were randomly to undergo either systematic prostate biopsy (systematic group) or targeted MRI/TRUS fusion prostate biopsy + systematic prostate biopsy (combined group). The clinical data and pathological results of biopsies were analyzed. RESULTS: The detection rate of PCa by targeted MRI/TRUS fusion prostate biopsy was higher than systematic prostate biopsy (38/81 vs. 33/81) in combinated group, but there was no significantly difference. The PCa detection rate in combinated group was significantly higher than systematic group (47/81 vs. 34/80, P = 0.049). There were 40 patients in combinated group and 22 patients in systematic group diagnosed as csPCa, respectively. The ratio of detected csPCa was much higher in combinated group (P = 0.032). In Gleason score no more than 6, the detected ratio of targeted MRI/TRUS fusion prostate biopsy was significantly lower than systematic biopsies in combinated group (P = 0.044). While, in Gleason score higher than 6, the detected ratios of targeted MRI/TRUS fusion prostate biopsy were all higher than systematic biopsies. CONCLUSIONS: Among patients with PI-RADS ≥ 3, targeted MRI/TRUS fusion prostate biopsy is superior to systematic prostate biopsy in the detection rate of PCa and csPCa, but it still misses some PCa patients, including csPCa. Combining targeted MRI/TRUS fusion prostate biopsy and systematic prostate biopsy can led to more detection of all PCas, especially csPCa.

Impact on sexual function of plasma button transurethral vapour enucleation versus plasmakinetic resection of the large prostate >90 ml: Results of a prospective, randomized trial.

To compare the impact of plasma button transurethral vapour enucleation of the prostate (PVEP) and plasmakinetic resection of the prostate (PKRP) on lower urinary tract symptoms and sexual function in patients with benign prostatic enlargement (BPE) >90 ml. Between July 2017 and August 2018, 101 patients with symptomatic BPE were randomly, prospectively assigned to either PKRP or PVEP in our department. The clinical characteristics and sexual function were evaluated before and after surgery. Post-void residual volume, IPSS and QoL were all significantly decreased compared with baseline data in each group, while Qmax was significantly increased. The IIEF-5 score showed a slight but nonsignificant increase in both groups at 3 and 6 months after surgery, and there was no significant difference between the two groups. The post-operative rate of reduced ejaculate volume was significantly higher than the pre-operative rate in PKRP group, while there was no significant difference in PVEP group. PVEP had an attenuated effect on no ejaculate compared with PRKP, and they both had a significantly negative effect on no ejaculate. PVEP is an effective and minimally invasive procedure for large prostate. Compared with PKRP, PVEP has no effect on erectile dysfunction and has a lower negative impact on ejaculation.

A rare case report of one stage surgical treatment for left renal cell carcinoma with level IV intravenous tumor thrombus combined with severe coronary artery stenosis.

RATIONALE: Renal cell carcinoma (RCC) exhibits a natural tendency to extend from the kidney into inferior vena cava (IVC) and growing into the right atrium is a rare complication. We report a 65-year-old patient with an RCC with intravascular extension through renal vein into the IVC and right atrial combined with severe coronary artery disease. This case has not been described in the literature and there is no treatment guideline for it. PATIENT CONCERNS: A 65-year-old patient was admitted to our clinic with complaints of edema of both lower extremities. DIAGNOSES: On the basis of the magnetic resonance imaging scan and coronary angiography, we strongly suspected an RCC with intravascular extension through renal vein into the IVC and right atrial combined with severe coronary artery disease. INTERVENTIONS: We performed open left radical nephrectomy, IVC, and right atrium thrombectomy under cardiopulmonary bypass and coronary artery bypass grafting on beating heart. OUTCOMES: The postoperative course was uneventful. The patient has been discharged from hospital. LESSONS: Coexistence of severe coronary artery disease and RCC infiltrating inferior vena cava and right atrium rendered this operation as very high-risk procedure. We hope that our operational manners can prove the possibility of simultaneous difficult cardiac and urologic operation. The basic point of our report concerns the fact that the oncologic treatment was not delayed despite severe heart disease.

ßKlotho inhibits androgen/androgen receptor­associated epithelial­mesenchymal transition in prostate cancer through inactivation of ERK1/2 signaling.

The epithelial­mesenchymal transition (EMT) is reported to have intimate crosstalk with androgen receptor (AR) signaling in prostate cancer (PCa) and is known to be responsible for castration resistance. Fibroblast growth factor/receptor (FGF/FGFR) signaling is also involved in tumor progression and EMT in multiple tissues. Several studies have investigated the role of ßKlotho, an FGF/FGFR signaling co­receptor in tumorigenesis. However, its role in PCa remains unknown. In the present study, the role of androgen in the EMT of PCa cells was examined by western blotting. The expression of ßKlotho was examined in prostate cells and PCa tissues by western blotting and immunohistochemistry, respectively. The biological role of ßKlotho was revealed by a series of functional in vitro and in vivo studies. We determined that ßKlotho expression was significantly decreased in PCa tissues compared with benign prostatic hyperplasia (BPH) tissues, and low ßKlotho expression was associated with a high Gleason score of PCa. ßKlotho overexpression inhibited the viability, migration, and androgen/AR­associated EMT of PCa cells through the inactivation of ERK1/2 signaling. Notably, ßKlotho overexpression inhibited prostate tumor growth and EMT in vivo. Knockdown of ßKlotho produced the opposite effects. In conclusion, ßKlotho inhibits EMT and plays a tumor­suppressive role in PCa, linking FGF/FGFR/ßKlotho signaling to the regulation of PCa progression.

Epigallocatechin-3-gallate ameliorates erectile function in aged rats via regulation of PRMT1/DDAH/ADMA/NOS metabolism pathway.

Aging-related ED is predominantly attributed to neurovascular dysfunction mediated by NO suppression and increased oxidative stress in penis. The alterations of protein arginine methyltransferases 1 (PRMT1)/dimethylarginine dimethylaminohydrolase (DDAH)/asymmetrical dimethylarginine (ADMA)/NO synthase (NOS) pathway regulate NO production in the vascular endothelium. Epigallocatechin-3-gallate (EGCG) is one of the most abundant and antioxidative ingredients isolated from green tea. In the present study, 40 Sprague-Dawley rats were randomly distributed into four groups: one young rat group and three aged rat groups treated with daily gavage feedings of EGCG at doses of 0, 10 mg kg-1 and 100 mg kg-1 for 12 weeks, respectively. Erectile function was assessed by electrical stimulation of the cavernous nerves with intracavernous pressure (ICP) measurement. After euthanasia, penile tissue was investigated using Western blot and ELISA to assess the PRMT1/DDAH/ADMA/NOS metabolism pathway. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected by colorimetry. We also evaluated smooth muscle contents. The ratio of maximal ICP and mean systemic arterial pressure (MAP) was markedly higher in EGCG-treated aged rats than in untreated aged rats. We found that DDAH1 and DDAH2 were expressed in cavernosal tissue, and they were downregulated in corpora of aged rats. The administration of EGCG upregulated the expression and activity of DDAH. In contrast, EGCG treatment downregulated the expression of PRMT1 and ADMA content. Moreover, EGCG-treated rats showed an improvement in smooth muscle expression, the ratio of smooth muscle cell/collagen fibril, SOD activity, and MDA levels when compared with untreated aged rats.

Bone mesenchymal stem cells differentiate into myofibroblasts in the tumor microenvironment.

The aim of the present study was to investigate the tropism of mesenchymal stem cells (MSCs) to the tumor microenvironment, and to evaluate the feasibility of bone marrow mesenchymal stem cells differentiating into myofibroblasts in vitro. A total of 1 ml bone marrow was extracted from the greater trochanter of one male New Zealand rabbit, and MSCs were obtained by density gradient centrifugation and cultured routinely. The surface markers were analyzed by flow cytometry. A VX2 tumor was aseptically excised from another male New Zealand rabbit and primary cultured. The tropism of MSCs for 30% and 50% VX2 conditioned medium was determined by using Transwell migration assays. MSCs were incubated in 30% VX2 conditioned medium for 7 or 14 days. The messenger (m)RNA levels and protein expression of α-smooth muscle actin (α-SMA) and vimentin were measured by reverse transcription-polymerase chain reaction and western blotting. MSCs were observed to have a spindle shape. The cultured MSCs were cluster of differentiation (CD)44+, CD105+, CD106+ and CD34-. VX2 cells demonstrated a spindle or polygon shape. In the Transwell assay, it was observed that the migrated cells appeared more frequently in the 30% VX2 conditioned medium group compared with the other groups when microscopically examined, which was additionally confirmed by the results of a colorimetric assay. The mRNA levels and protein expression of α-SMA and vimentin significantly increased in the test group compared with the control group at 7 days (P<0.01), and further increased in the test group at 14 days (P<0.01). The results of the present study demonstrated that MSCs have tropism for the tumor microenvironment and furthermore, may differentiate into myofibroblasts in the tumor microenvironment in vitro. The present study suggested that MSCs may migrate to the tumor and subsequently differentiate into myofibroblasts due to the tumor microenvironment, which may lead to promotion of the growth of the tumor. The present study additionally suggested that MSCs may be the precursors of tumor/carcinoma-associated myofibroblasts.

Probucol Improves Erectile Function by Restoring Endothelial Function and Preventing Cavernous Fibrosis in Streptozotocin-induced Diabetic Rats.

OBJECTIVE: To investigate the effects of probucol on erectile function in streptozotocin-induced diabetic rats and explore the underlying mechanisms. METHODS: A total of thirty 12-week-old Sprague-Dawley male rats received a 1-time intraperitoneal streptozotocin (60 mg/kg) or vehicle injection after a 12-hour fast. Three days later, the streptozotocin-induced diabetic rats were randomly divided into 2 groups and were treated with daily gavage feedings of probucol at doses of 0 and 500 mg/kg for 12 weeks. A positive control group underwent intraperitoneal injection of saline followed by daily gavage of saline solution. Erectile function was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure measurement. After euthanasia, penile tissue was investigated using immunohistochemistry, Western blot, and ELISA to assess the protein arginine-N-methyltransferase 1/dimethylarginine dimethylaminohydrolase/asymmetric dimethylarginine/nitric oxide synthase metabolism pathway. Superoxide dismutase activity and malondialdehyde levels were detected by colorimetry. We also evaluated penile histological changes such as smooth muscle contents and Masson's trichrome stain. RESULTS: Significant recovery of erectile function was observed in the probucol-treated rats than the untreated diabetic rats. The protein expression of dimethylarginine dimethylaminohydrolase and nitric oxide synthase, cyclic guanosine monophosphate concentrations, and superoxide dismutase activity in cavernous tissue of probucol-treated rats were significantly higher than the untreated diabetic rats. The protein expression of protein arginine-N-methyltransferase 1, asymmetric dimethylarginine concentrations, and malondialdehyde levels in cavernous tissue of probucol-treated rats were significantly lower than the untreated diabetic rats. In addition, probucol treatment markedly augments the cavernous smooth muscle content. CONCLUSION: Probucol treatment improves erectile function by restoring endothelial function and preventing cavernous fibrosis in streptozotocin-induced diabetic rats.

Plasmakinetic Vapor Enucleation of the Prostate with Button Electrode versus Plasmakinetic Resection of the Prostate for Benign Prostatic Enlargement >90 ml: Perioperative and 3-Month Follow-Up Results of a Prospective, Randomized Clinical Trial.

OBJECTIVE: To evaluate plasmakinetic vapor enucleation of the prostate (PVEP) with button electrode and plasmakinetic resection of the prostate (PKRP) in patients with urinary symptoms due to benign prostatic enlargement (BPE) >90 ml. METHODS: A total of 112 patients with symptomatic BPE were randomly assigned to either PKRP or PVEP prospectively from August 2012 to May 2014 in our department. Perioperative and postoperative data were investigated during a 3-month follow-up. RESULTS: PVEP was significantly superior to PKRP in terms of operation time (63.9 ± 7.7 vs. 78.1 ± 13.6 min, p < 0.001), hemoglobin loss (1.18 ± 0.30 vs. 1.63 ± 0.38 g/dl, p < 0.001), serum sodium decrease (2.9 ± 0.7 vs. 4.3 ± 0.8 mmol/l, p < 0.001), catheterization duration (49.3 ± 12.2 vs. 78.1 ± 14.8 h, p < 0.001) and hospital stay (100.2 ± 28.3 vs. 116.0 ± 29.2 h, p = 0.004). There were no statistical differences in blood transfusion between the two groups. In addition, there were no statistical differences in maximum urinary flow rate, International Prostate Symptom Score, postvoid residual urine volume, quality-of-life score, transient incontinence, and urethral stricture at 3 months postoperatively. CONCLUSIONS: PVEP with button electrode is an equally effective technique for treatment of large BPE with PKRP, with more safety and faster recovery. It may become the superior alternative to PKRP for patients with large BPE.

MK2206 potentiates cisplatin-induced cytotoxicity and apoptosis through an interaction of inactivated Akt signaling pathway.

OBJECTIVES: To improve conventional chemotherapeutic efficacy, it is important to detect new molecular markers for chemosensitivity and possible accelerating cell-killing mechanisms. In this study, we investigated how MK2206, an allosteric Akt inhibitor, enhances the cisplatin (CDDP)-induced cytotoxicity and apoptosis in urothelial cancer cells. MATERIALS AND METHODS: We examined bladder cancer cell lines for the expression of phospho(p)-Akt and its downstream targets by Western blot. The potential antitumor effects were analyzed by MTT assay in vitro and by subcutaneous xenograft models in vivo. The cell invasion was examined by transwell invasion assay, and the activities of the Akt signaling pathway and expression of apoptosis-related proteins were measured by Western blot. RESULTS: The expression of p-Akt and its downstream targets was increased in invasive bladder cancer cell lines vs. in noninvasive bladder cancer cell lines. MK2206 (500 nM) inhibited cell invasion in UMUC3 cell line and significantly increased the susceptibility of bladder cancer cell lines to CDDP. When used in combination with CDDP, MK2206 (500 nM) enhanced CDDP-induced cytotoxicity and apoptosis, with suppressed expression of p-Akt and its downstream targets. In vivo MK2206 combined with CDDP effectively suppressed tumor growth in subcutaneous xenograft models. CONCLUSIONS: These results suggest that concomitant use of MK2206 could promote the CDDP-induced cytotoxicity and apoptosis in urothelial cancer cell lines through the inhibited expression of the Akt pathway. This combined treatment may provide a new therapeutic option to enhance chemosensitivity in bladder cancer.