Yuxi Shan

The application of 120-W high-performance system GreenLight laser vaporization of the prostate in high-risk patients

The purpose of this study is to evaluate the safety and efficacy of 120-W potassium titanyl phosphate (KTP) laser vaporization in patients with benign prostatic hyperplasia (BPH) who also had cardiopulmonary diseases who were taking long-term anticoagulants and were at high risk of bleeding complications. The prospective study included 188 patients with severe lower urinary tract symptoms who underwent 120-W KTP laser vaporization of the prostate. All patients were at high cardiopulmonary risk, having presented with an American Society of Anesthesiology score of 3 or greater. Of those, 45 patients were taking oral anticoagulants, and 1 had a severe bleeding disorder. BPH was successfully treated with 120-W KTP laser vaporization in all patients. Mean preoperative prostate volume ± SD was 66u2009±u200923.1xa0ml, and mean operative time was 50.8u2009±u200915.5xa0min. There were no major complications intraoperatively or postoperatively, and no blood transfusions were required. Postoperatively, only 14 patients (7.4xa0%) required bladder irrigation. Average catheterization time was 1.9u2009±u20091.5xa0days (range, 1–5xa0days). Three patients required reoperation due to enlarged prostates from residual adenoma. At 3-, 6,- 12-, and 24-month follow-ups, mean urinary peak flow increased from 8.0u2009±u20093.6xa0ml/s to 19.1u2009±u20095.6, 19.2u2009±u20094.7, 19.1u2009±u20094.65, and 19.2u2009±u20094.34xa0ml/s, respectively. Mean International Prostate Symptom Scores decreased over time, from 25.6u2009±u20095.1 (3xa0months) to 9.4u2009±u20092.8, 7.05u2009±u20091.46, 6.24u2009±u20091.36, and 6.20u2009±u20091.32 (24xa0months), respectively. 120-W HPS KTP laser vaporization is a safe and effective treatment option in BPH patients at high risk and those on anticoagulation therapy who have severe LUTS secondary to BPH.

SATB1 promotes prostate cancer metastasis by the regulation of epithelial-mesenchymal transition.

Special AT-rich sequence binding protein 1 (SATB1) plays important role in the regulation of chromatin structure and gene expression. Recent studies have indicated oncogenic role of SATB1. However, the function of SATB1 in prostate cancer progression and metastasis remains unclear. In this study SATB1 expression vector or siRNA was employed to modulate the expression level of SATB1 in prostate cancer cells and xenograft tumor in nude mouse model. Immunohistochemical analysis was performed on clinical prostate cancer samples. Silencing SATB1 inhibited the growth of DU-145 cells subcutaneous tumor in nude mice, while SATB1 overexpression promoted the growth of LNCaP cells subcutaneous tumor in nude mice. Immunohistochemical and Western blot analysis of the xenografts showed that silencing SATB1 led to decreased expression of vimentin and MMP2 and increased expression of E-cadherin, while SATB1 overexpression led to increased expression of vimentin and MMP2 and decreased expression of E-cadherin. Furthermore, SATB1, vimentin and MMP2 expression was increased significantly while E-cadherin expression was reduced significantly in clinical samples of prostate carcinoma with metastasis compared to prostate carcinoma without metastasis and benign prostate hyperplasia. Taken together, these findings suggest that the modulation of epithelial-mesenchymal transition by SATB1 may contribute to prostate cancer metastasis.

Oncolytic virus carrying shRNA targeting SATB1 inhibits prostate cancer growth and metastasis

Recent studies suggest that SATB1 is a promising therapeutic target for prostate cancer. To develop novel SATB1-based therapeutic agents for prostate cancer, in this study, we aimed to construct ZD55-SATB1, an oncolytic adenovirus ZD55 carrying shRNA targeting SATB1, and investigate its effects on the inhibition of prostate cancer growth and metastasis. ZD55-SATB1 was constructed and used to infect human prostate cancer cell lines DU145 and LNCaP. The inhibitory effect of ZD55-SATB1 on SATB1 expression was evaluated by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The cytotoxicity of ZD55-SATB1 was detected by MTT assay. Cell invasion was detected by Matrigel invasion assay. The in vivo antitumor activities of ZD55-SATB1 were evaluated in xenograft mouse model. We found that ZD55-SATB1 selectively replicated and significantly reduced SATB1 expression in DU145 and LNCaP cells. ZD55-SATB1 effectively inhibited the viability and invasion of DU145 and LNCaP cells in vitro and inhibited prostate cancer growth and metastasis in xenograft nude mice. In conclusion, replicative oncolytic adenovirus armed with SATB1 shRNA exhibits effective antitumor effect in human prostate cancer. Our study provides the basis for the development of ZD55-SATB1 for the treatment of prostate cancer.

IL-12 and IL-10 Production are Differentially Regulated by Phosphatidylinositol 3-Kinase in Mast Cells

The cellular mechanisms that directly regulate the production of pro‐ and anti‐inflammatory cytokines after lipopolysaccharide (LPS) stimulation in mast cells are currently unresolved. The aim of this study was to clarify the role of phosphatidylinositol 3‐kinase (PI3K) in the production of IL‐12 and IL‐10 in mouse bone marrow‐derived mast cells (BMMCs), stimulated with Escherichia coli‐derived LPS. LPS activates the PI3K signalling pathway; analysis of cytokine production following LPS stimulation of BMMCs revealed that inhibition of the PI3K pathway differentially regulated IL‐10 and IL‐12 syntheses. IL‐12 production was enhanced, whereas IL‐10 levels were suppressed. Inhibition of LPS‐mediated activation of the PI3K pathway resulted in a pronounced reduction of NF‐κB activity that was dependent on IκBα phosphorylation. These findings demonstrate a regulatory function for PI3K in modulating IL‐10 and IL‐12 production in mast cells and provide insight into how engagement of the PI3K pathway affects the induction of key immunoregulatory cytokines that control both qualitative and quantitative aspects of early inflammation.

Photoselective Vaporization of the Prostate with GreenLight HPS 120-W Laser for Benign Prostatic Hyperplasia: 36 Months’ Follow-Up

Objective: To evaluate the 3-year clinical outcomes and durability of photoselective vaporization of the prostate (PVP) with the GreenLight HPS laser in the treatment of symptomatic and obstructive benign prostatic hyperplasia (BPH). Methods: A total of 78 patients underwent PVP with the GreenLight HPS laser from October 2007 to November 2008. The baseline and treatment outcomes after surgery were evaluated 3 years later with the International Prostate Symptom Score (IPSS), quality of life (QoL), maximum flow rate (Qmax), postvoid residual rate (PVR), and transrectal ultrasound-determined prostate volume. These parameters were assessed at 1, 3, 6, 12, 24, and 36 months. Results: Patients’ urinary symptoms and QoL significantly improved after surgery. The functional outcomes showed immediate and stable improvements during the entire follow-up period. At 36 months, the average percentage of improvements compared with baseline was as follows: IPSS, 60.2%; QoL, 80.9%; Qmax, 138.7%, and PVR, 82.6%. The median prostate volume, evaluated by transrectal ultrasonography, showed a 50.4% reduction when compared to preoperative volume. Overall, complications from surgery were low; only 6.7% of the 75 patients required reoperation during the 3-year follow-up. Conclusion: PVP using the GreenLight HPS laser showed a safe and effective treatment outcome for the treatment of symptomatic and obstructive BPH.

Dual role of TGFBR3 in bladder cancer.

Bladder cancer is one of the most common genitourinary malignant diseases worldwide. More than 90% of bladder cancer cases are bladder urothelial carcinoma (BUC). Although transforming growth factor-β III receptor (TGFBR3) has been suggested to play a dual role in cancer progression, little is known about TGFBR3 in bladder cancer. In the present study, fresh tumor and the corresponding paracarcinoma tissue specimens were collected from 56 bladder urothelial carcinoma patients. TGFBR3 expression in these tissues was determined by western blotting. TGFBR3 was also detected in the human normal urothelial cell line SV-HUC-1, the human superficial urothelial bladder cancer cell line 5637, and the human invasive bladder cancer cell line T24 using western blotting and quantitative PCR. Cell growth, motility and invasion were also analyzed in the control and the TGFBR3 gene-silenced T24 cells. As a result, the expression of TGFBR3 was reduced (18/30) in most superficial bladder urothelial carcinoma tissues compared to the corresponding normal tissues, whereas TGFBR3 expression was more enhanced (19/26) in the invasive samples. Similarly, an increase of TGFBR3 expression was found in T24 cells, but a decrease was observed in 5637 cells. Knockdown of TGFBR3 in T24 cells resulted in decreased cell growth, motility and invasion. In conclusion, these findings suggest that TGFBR3 may play a dichotomous role in human bladder cancer, acting as both a tumor suppressor and as a tumor promoter.

GreenLight HPS 120-W laser photoselective vaporization of the prostate as early therapy for acute urinary retention in advanced prostate cancer patients.

We evaluate the safety, efficacy, and oncological outcomes of early palliative photoselective vaporization of the prostate (PVP) by GreenLight high-performance system (HPS) 120-W laser in patients with acute urinary retention (AUR) induced by advanced prostate cancer (PCa). A total of 39 advanced PCa patients with AUR who underwent PVP were enrolled in this retrospective study. Baseline parameters, perioperative, and postoperative complications were reviewed. The functional outcomes were evaluated at 1, 3, 6, and 12xa0months after surgery using the International Prostate Symptom Score (IPSS), quality of life (QoL) score, peak urinary flow rate (Qmax), and postvoid residual urine volume (PVR). At baseline, mean age was 72.8u2009±u20096.8xa0years and mean prostate-specific antigen (PSA) level was 45.2u2009±u200926.9xa0ng/mL. The average energy consumed was 171.2u2009±u200972.3xa0kJ during a mean operative time of 46.3u2009±u200913.7xa0min. Mean catheterization duration was 3.3u2009±u20090.8xa0days. Mean hospitalization time was 5.2u2009±u20090.5xa0days. Compared with the preoperative values, there were significant continuous improvement in IPSS, QoL score, Qmax, and PVR at all time points of follow-up. The mean PSA nadir was 0.33u2009±u20090.15xa0ng/mL and the mean time to PSA nadir was 10.3u2009±u20092.5xa0months. Nine patients (23xa0%) eventually developed hormone refractory prostate cancer. No patient experienced severe intraoperative and postoperative complications. Our preliminary investigation shows that GreenLight HPS 120-W laser PVP is a safe and effective treatment for advanced PCa patients with AUR. Patients may obtain some oncological benefits from tumor cytoreduction by early palliative PVP.

Photoselective vaporization of the prostate with GreenLight 120-W laser versus transurethral resection of the prostate for benign prostatic hyperplasia: a systematic review with meta-analysis of randomized controlled trials

The aim of this study is to assess the overall efficacy and safety of photoselective vaporization of the prostate (PVP) with GreenLight 120-W laser versus transurethral resection of the prostate (TURP) for treating patients of benign prostate hyperplasia (BPH) with lower urinary tract symptoms (LUTS). We performed a literature search of The Cochrane Library and the electronic databases, including Embase, Medline, and Web of Science. Manual searches were conducted of the conference proceedings, including European Association of Urology and American Urological Association (2007 to 2012). Outcomes reviewed included clinical baseline characteristics, perioperative data, complications, and postoperative functional results, such as postvoid residual (PVR), international prostate symptom score (IPSS), quality of life (QoL), and maximum flow rate (Qmax). Six randomized controlled trials (RCTs) were enrolled. Three hundred and forty-seven patients undergone 120-W PVP, and 350 patients were treated with TURP in the RCTs. There were no significant differences for clinical characteristics in these trials. In perioperative data, catheterization time and length of hospital stay were shorter in the PVP group. However, the operation time was shorter in the TURP group. Capsular perforation, blood transfusion, clot retention, and macroscopic hematuria were markedly less likely in PVP-treated subjects. The other complications between PVP and TURP did not demonstrate a statistic difference. There were no significant differences in QoL, PVR, IPSS, and Qmax in the 1, 3, 6, 12, and 24xa0months of postoperative follow-up. There was no significant difference at postoperation follow-up of functional outcomes including IPSS, PVR, Qmax, and QoL between the TURP-treated subjects and PVP-treated subjects. Owing to a shorter catheterization time, reduced hospital duration and less complication, PVP could be used as an alternative and a promising minimal invasive surgical procedure for the treatment of BPH.

Expression and prognostic significance of ELL-associated factor 2 in human prostate cancer

AbstractPurposeELL-associated factor 2 (EAF2) is an androgen-regulated tumor suppressor in the prostate. The purpose of this study was to investigate the expression of EAF2 protein in human prostate cancer specimens along with BPH specimens as a control, and to evaluate potential association of EAF2 expression with clinical characteristics and overall survival of the prostate cancer patients.MethodsnThe expression of EAF2 was evaluated in 44 prostate cancer and 23 BPH tissue specimens using immunohistochemistry. The relationships of EAF2 expression with clinical characteristics and overall survival rates were analyzed by Chi-square test and Kaplan–Meier method.ResultsThe immunostaining intensity of EAF2 in BPH specimens was significantly higher than that in prostate cancer (pxa0<xa00.05). EAF2 expression decreased significantly in high-grade and advanced-stage human prostate tumors and inversely correlated with PSA level, Gleason scores, bone metastasis and tumor stage. Importantly, loss of EAF2 expression was associated with a significant decrease in patient survival.ConclusionExpression of EAF2 is decreased in prostate carcinogenesis, and EAF2 loss is associated with high-risk patients and poor survival.

TGFBR3 Co‐Downregulated With GATA3 Is Associated With Methylation of the GATA3 Gene in Bladder Urothelial Carcinoma

Bladder urothelial carcinoma (BUC) accounts for ∼90% of all cases of bladder cancer. Reduced expression of TGFBR3 has been frequently observed in several types of human cancers. However, little is known about whether expression of TGFBR3 reduced in BUC and the underlying mechanisms. In the present study, we performed quantitative real‐time PCR to examine the mRNA expression of TGFBR3 and GATA3, and bisulfite genomic sequencing to evaluate the methylation status in TGFBR3 and GATA3 promoter regions in fresh tumor and the corresponding paracarcinoma tissues from 29 patients with BUC. As a result, the expression of TGFBR3 and GATA3, a transcriptional factor of the TGFBR3 gene, were found to be co‐downregulated in BUC. Moreover, our findings indicated that GATA3 promoter methylation was one of the reasons for silencing of GATA3 and TGFBR3 in BUC, albeit TGFBR3 methylation and mutation were not associated with reduced expression of TGFBR3 mRNA in BUC. In summary, our findings suggest that methylation in the GATA3 promoter region may inhibit the expression of GATA3 mRNA, which leads to the reduced expression of TGFBR3 mRNA in BUC. Anat Rec, 296:1717–1723, 2013.