Yeping Liang

The Characteristics of the Stone and Urine Composition in Chinese Stone Formers: Primary Report of a Single-center Results

OBJECTIVE To assess urine composition in Chinese patients with urolithiasis. METHODS Five hundred seven Chinese patients with urolithiasis from our center in southern China were included in this study. Analysis of stone composition was performed using infrared spectrometry. From all patients, 24-hour urine samples were collected for analysis of urinary variables. Some ion activity product risk indices were also calculated. RESULTS The major stone constituents in the 507 analyzed stones were as follows: calcium oxalate (78.3%), infection stone components (14.6%), uric acid (3.6%), and calcium phosphate (3.4%). Only 1 stone was composed of cystine (0.2%). Of all patients, 504 (99.4%) had 1 or several urinary metabolic abnormalities. Hypocitraturia was recorded in 93.9%, high sodium excretion in 58.6%, small urine volume in 45.6%, hyperoxaluria in 31.0%, hypercalciuria in 26.0%, hyperuricosuria in 19.3%, and hyperphosphaturia in 2.8%. Moreover, high sodium excretion was more frequent in men than women (59.2% vs 49.3%, P = .027), whereas hypercalciuria was more common in women (34.5% vs 20.4%, P <.001). High levels of urine sodium (187.7 ± 86.9 vs 179.8 ± 107.7 mmol/24h, P = .038) and phosphate (18.26 ± 8.36 vs 15.69 ± 11.14 mmol/24h, P <.001) were found in men than in women. Infection stones were significantly (P <.004) more common in women. Compared with noninfection stone formers, the occurrence of hypomagnesuria (P = .040) was more common in patients with infection stones. CONCLUSION The results of urinary risk factors for stone formation in this study might serve as a basis for design of recurrence prevention. It is of interest to note that some of the demonstrated abnormalities differ from that in reports from other countries.

Small interference RNA-mediated silencing of prostate stem cell antigen attenuates growth, reduces migration and invasion of human prostate cancer PC-3M cells

OBJECTIVES Prostate stem cell antigen (PSCA), a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein, is highly expressed in both local and metastatic prostate cancer (CaP). Elevated PSCA expression has been shown to correlate with malignant phenotype and clinical progression. The purpose of the current study is to investigate the therapeutic potential of small interference RNA (siRNA) targeting PSCA on human CaP cells. MATERIALS AND METHODS A set of two siRNAs directed different regions of human PSCA (siRNA-PSCA) were designed and transfected into a human CaP PC-3M cell line. The silencing effect was screened by RT-PCR and Western blotting. The biological effects of siRNA-PSCA on PC-3M cells were investigated by examining the cell proliferation through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle distribution through flow cytometry, and migration and invasion potencies through transwell invasion assay upon the PSCA silencing. RESULTS PC-3M cells had positive PSCA expression on immunocytochemical assay. PSCA expression was depleted at 48 hours after transfection with siRNA-PSCA. Silencing of PSCA significantly suppressed cell proliferation. Cell cycle assay showed that the anti-proliferation effect of siRNA-PSCA was mediated by arresting cells in the G0/G1 phase rather than apoptosis. Furthermore, PSCA knockdown resulted in a marked decrease of cell migration and invasion capabilities in PC-3M cells. CONCLUSIONS The present study provides the first evidence that silencing PSCA using siRNA can inhibit the proliferation and invasiveness properties of human CaP cells, which may provide a promising therapeutic strategy for CaP and open a novel avenue toward the investigation of the role of PSCA overexpression in cancers.

Peripheral blood reverse transcription PCR assay for prostate stem cell antigen correlates with androgen-independent progression in advanced prostate cancer

Recent studies show that prostate stem cell antigen (PSCA) mRNA positivity in peripheral blood correlates with disease progression in prostate cancer (PCa). Our study is to evaluate the association between peripheral blood PSCA status and androgen‐independent progression (AIP) in a cohort of patients with advanced PCa under androgen deprivation therapy (ADT). PSCA mRNA was measured by reverse transcriptase polymerase chain reaction (RT‐PCR) assay in peripheral blood samples from 116 patients with locally advanced or metastatic PCa who were treated with primary ADT and from 40 healthy controls. The Kaplan–Meier and the Cox proportional hazards methods were used to assess potential predictors of AIP. Pretreatment RT‐PCR‐PSCA was positive in 37 (31.9%) of 116 patients. All healthy volunteers were negative for PSCA mRNA. Although seven (14.9%) of 47 patients with Gleason score ≤7 were PSCA positive, 30 (43.5%) of 69 patients with Gleason score >7 were PSCA positive (p = 0.016). PSCA mRNA was detected in 28 (58.3%) of 48 patients with metastatic PCa, compared to nine (13.2%) of 68 patients with locally advanced disease (p = 0.012). AIP developed in 59 (50.9%) patients during a median follow‐up period of 35.4 months (range: 4–78 months). Patients with PSCA negativity experienced significantly longer remissions compared to those with PSCA positivity (log‐rank test: p < 0.001). Multivariate Cox regression analysis further demonstrated that PSCA positivity had a significantly increased risk of AIP (HR = 4.303, 95% CI: 3.761–7.482, p < 0.001). Pretreatment RT‐PCR PSCA positivity in peripheral blood independently signals the presence of AIP in patients with advanced PCa treated with ADT.

Impact of Plasmakinetic Enucleation of the Prostate (PKEP) on Sexual Function: Results of a Prospective Trial

INTRODUCTION Recent data have shown that plasmakinetic enucleation of the prostate (PKEP) is a novel and effective procedure for symptomatic benign prostatic hyperplasia (BPH); however, data on patient sexual function after PKEP remain scarce. AIMS This study aims to evaluate the impact of PKEP on sexual function in men with lower urinary tract symptoms because of BPH. METHODS One hundred eighty-six consecutive patients who underwent the PKEP procedure were prospectively enrolled in this study. The International Index of Erectile Function (IIEF-15) and the International Prostate Symptom Score with quality of life scores were completed and compared preoperatively and at 1, 3, 6, and 12 months postoperatively. At each follow-up visit, maximum urinary flow rates, transrectal ultrasound-assessed prostate volume, postvoid residual urine volume, and serum prostate-specific antigen level were also measured and compared with the baseline. MAIN OUTCOME MEASURES The IIEF global score and its five domains scores were evaluated for each patient, and the Friedman test or chi-square test was used to identify changes from the baseline. RESULTS There was a slight and nonsignificant increase in the IIEF global score and four of its five domains scores (i.e., erectile function, intercourse satisfaction, sexual desire, and overall satisfaction) at each postoperative assessment (P > 0.05 for all). However, a statistically significant reduction was observed in the orgasmic function domain score of IIEF at 3 months (P = 0.016), 6 months (P < 0.001), and 12 months (P < 0.001), respectively, along with the corresponding retrograde ejaculation rates of 48.7%, 49.4%, and 48.8%. CONCLUSIONS PKEP has no negative influence on the quality of erections measured by the self-administered IIEF questionnaire, but it significantly lowers the orgasmic function domain score, reflecting probably postoperative retrograde ejaculation. These findings are important in preoperative counseling of the patients undergoing PKEP for symptomatic BPH.

Preoperative serum levels of early prostate cancer antigen (EPCA) predict prostate cancer progression in patients undergoing radical prostatectomy.

Early prostate cancer antigen (EPCA) has been shown a prostate cancer (PCa)‐associated nuclear matrix protein, however, its serum status and prognostic power in patients with PCa are unknown. The goals of this study are to measure preoperative serum EPCA levels in a cohort of PCa patients who were treated with radical prostatectomy (RP), and to investigate whether serum EPCA levels would independently predict cancer prognosis after the surgery.

Inhibition of PARP1 by small interfering RNA enhances docetaxel activity against human prostate cancer PC3 cells

Though poly(ADP-ribose) polymerase 1 (PARP1) inhibitors have benefits in combination with radiotherapy in prostate cancers, few is known about the exactly role and underlying mechanism of PARP1 in combination with chemotherapy agents. Here our data revealed that inhibition of PARP1 by small interfering RNA (siRNA) could enhance docetaxels activity against PC3 cells, which is associated with an accelerate repression of EGF/Akt/FOXO1 signaling pathway. Our results provide a novel role of PARP1 in transcription regulation of EGFR/Akt/FOXO1 signaling pathway and indicate that PARP1 siRNA combined with docetaxel can be an innovative treatment strategy to potentially improve outcomes in CRPC patients.

Serum early prostate cancer antigen (EPCA) level and its association with disease progression in prostate cancer in a Chinese population.

Background Early prostate cancer antigen (EPCA) has been shown a prostate cancer (PCa)-associated nuclear matrix protein, however, its serum status and prognostic power in PCa are unknown. The goals of this study are to measure serum EPCA levels in a cohort of patients with PCa prior to the treatment, and to evaluate the clinical value of serum EPCA. Methods Pretreatment serum EPCA levels were determined with an ELISA in 77 patients with clinically localized PCa who underwent radical prostatectomy and 51 patients with locally advanced or metastatic disease who received primary androgen deprivation therapy, and were correlated with clinicopathological variables and disease progression. Serum EPCA levels were also examined in 40 healthy controls. Results Pretreatment mean serum EPCA levels were significantly higher in PCa patients than in controls (16.84±7.60 ng/ml vs. 4.12±2.05 ng/ml, P<0.001). Patients with locally advanced and metastatic PCa had significantly higher serum EPCA level than those with clinically localized PCa (22.93±5.28 ng/ml and 29.41±8.47 ng/ml vs. 15.17±6.03 ng/ml, P = 0.014 and P<0.001, respectively). Significantly elevated EPCA level was also found in metastatic PCa compared with locally advanced disease (P<0.001). Increased serum EPCA levels were significantly and positively correlated with Gleason score and clinical stage, but not with PSA levels and age. On multivariate analysis, pretreatment serum EPCA level held the most significantly predictive value for the biochemical recurrence and androgen-independent progression among pretreatment variables (HR = 4.860, P<0.001 and HR = 5.418, P<0.001, respectively). Conclusions Serum EPCA level is markedly elevated in PCa. Pretreatment serum EPCA level correlates significantly with the poor prognosis, showing prediction potential for PCa progression.

Terazosin Suppress Human Prostatic Cancer PC3 Cell Viability via Proteasome Inhibition

Terazosin is one of classic quinazoline-based selective α1-adrenoreceptor antagonists, which is usually used for the treatment of benign prostate hyperplasia (BPH) patients. Several evidences suggest that terazosin can induce apoptosis of prostatic cancer cells in vitro and suppress prostatic tumor growth in vivo, but molecular mechanism contributing to these processes has not yet been fully elucidated. In this study, we report that the suppression of terazosin on prostatic cancer PC3 cells viability partially mediated by proteasome inhibition. We first examined cytotoxicity of terazosin in human prostatic cancer cell line PC3, including cell viability, cell cycle analysis and cell apoptosis analysis. Then the chymotrypsin-like proteasome activity, levels of ubiquitinated-proteins and selective protein substrate of proteasome were detected, to reflect alteration of proteasome activity. Our results indicate that terazosin treatment results in a significant decrease of cell viability in a dose- and time- dependent manner in PC3 cells, accompanied with cell cycle arrest and apoptotic induction; Exposure to terazosin also causes a significant loss of proteasome activity as well as accumulation of ubiquitinated-proteins and selective protein substrate P27 in PC3 cells, which occurs prior to cell death. In view of these results, we conclude that terazosin suppress human prostatic cancer PC3 cell viability by cell cycle arrest and cell death induction, which is associated with its proteasome inhibitory activity.

Interconversion of stone composition profiles from two recurrent stone episodes in stone formers

Abstract Background: The aim of the study was to investigate the interconversion of the stone chemical composition of two recurrent stone episodes in stone formers. Methods: The data of 1098 stones analyses from 549 patients with a history of two renal stone episodes were selected and reviewed. The stone composition between the two recurrent episodes of stones was compared. Results: The percent occurrences of stones caused by infection, known as infection stones, in new episodes of stones significantly increased by 7% and uric acid stones increased by 3.8% while the calcium oxalate stones decreased by 13.1% (each p<0.05). The mean recurrent interval of new episodes of stones was 34.2 months. Infection stones had a significant shorter interval time compared to calcium oxalate stones (p<0.001). On a patient-by-patient investigation, 32.9% of patients underwent conversions of stone compositions, with 31.9% and 34.1% in men and female, respectively (p=0.590). The mutual conversion of infection stones to calcium oxalate stones was most common. The 61.1% of patients with uric acid recurrent stones were composed of calcium oxalate in the previous episode of stones, and 5% and 51.7% of patients with infection stones developed stones of uric acid or calcium oxalate in the new episode, respectively. Conclusions: Alterations of stone components during follow-up were found in as high as 32.9% of patients with no gender difference. The impetus of these shifts is not readily apparent. Accurate and repeated stone analyses throughout the course of recurrent stone disease are highly warranted, which may be useful to prevent recurrence of composition-specific stones.