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The tumorigenic role and underlying mechanisms of lipid accumulation, commonly observed in many cancers, remain insufficiently understood. In this study, we identified an AMP-activated protein kinase (AMPK)–GATA-binding protein 3 (GATA3)–enoyl-CoA hydratase short-chain 1 (ECHS1) pathway that induces lipid accumulation and promotes cell proliferation in clear cell renal cell carcinoma (ccRCC). Decreased expression of ECHS1, which is responsible for inactivation of fatty acid (FA) oxidation and activation of de novo FA synthesis, positively associated with ccRCC progression and predicted poor patient survival. Mechanistically, ECHS1 downregulation induced FA and branched-chain amino acid (BCAA) accumulation, which inhibited AMPK-promoted expression of GATA3, a transcriptional activator of ECHS1. BCAA accumulation induced activation of mTORC1 and de novo FA synthesis, and promoted cell proliferation. Furthermore, GATA3 expression phenocopied ECHS1 in predicting ccRCC progression and patient survival. The AMPK–GATA3–ECHS1 pathway may offer new therapeutic approaches and prognostic assessment for ccRCC in the clinic. Significance: These findings uncover molecular mechanisms underlying lipid accumulation in ccRCC, suggesting the AMPK–GATA3–ECHS1 pathway as a potential therapeutic target and prognostic biomarker.

To investigate the changes in the size of the penis after radical prostatectomy (RP) and the possible influencing factors.This study included 45 cases of RP for PCa performed by the same surgeon from January to June 2019. Before and at 2 weeks after surgery, we measured the stretched penile length (SPL), flaccid penile length (FPL) and penile circumference of the patients. We conducted an IIEF-5 questionnaire investigation on the preoperative characteristics of the patients and their attitudes towards postoperative penile rehabilitation. We also analyzed the factors associated with the postoperative changes in the size of the penis.Compared with the baseline, the postoperative SPL (［9.72 ± 1.87］ vs ［7.80 ± 1.57］ cm, P = 0), FPL (［6.26 ± 1.14］ vs ［5.13 ± 1.10］ cm, P = 0) and penile circumference (［7.69 ± 0.83］ vs ［7.26 ± 0.78］ cm, P = 0.012) were decreased significantly, by (1.92 ± 0.12) cm, (1.13 ± 0.09) cm and (0.43 ± 0.08) cm, respectively. The age of the patients was significantly correlated with the change of the FPL (P = 0.042), but not the other factors with the change of the penile size. Twenty-six (57.7%) cases of severe and moderate ED were observed in the patients postoperatively. Those with better preoperative sexual function took a more positive attitude towards penile rehabilitation and treatment postoperatively (n = 3, 75.0%).The penile size of the PCa patient is decreased markedly after radical prostatectomy, with a significant correlation between the patient's age and the postoperative change of the flaccid penile length. The patients with better preoperative sexual function are more likely to seek penile rehabilitation and treatment postoperatively.

Commutation failures are very common in LCC-based HVDC systems, and many control strategies have been developed to enhance the immunity against commutation failures. Among these strategies, one key idea is to enlarge the commutation margin by firing the gate with a specific time advance. However, the controllers based on PI-scheme may induce unexpected overshoot, leading to the failure of recovery. A recovery strategy to eliminate the overshoot is proposed for improving the performance of recovery from commutation failures, where the fast-changing trend of system states including commutating voltage and dc current are considered. Case studies show the effectiveness of the proposed method.

To investigate the attitudes of prostate cancer (PCa) patients towards postoperative penile rehabilitation and their influencing factors.Seventy-nine PCa patients underwent radical prostatectomy from January through June 2017 and all received a questionnaire investigation before surgery on IIEF-5 and their attitudes towards postoperative penile rehabilitation. We analyzed the reasons for the patients' rejection of postoperative penile rehabilitation.Totally 56 (71%) of the patients accepted and the other 23 (29%) refused postoperative penile rehabilitation. The factors influencing their attitudes towards penile rehabilitation mainly included age (P = 0.023), income (P = 0.040), tumor stage (P = 0.044), and preoperative sexual activity (P = 0.004). The patients who accepted penile rehabilitation had significantly higher IIEF-5 scores than those who refused it (14.75 ± 0.88 vs 8.48 ± 1.16, P = 0.000 2). During the follow-up period, only 29 (36.7%) of the patients bought the vacuum erection device but not the other 50 (63.3%). The tumor stage (P = 0.004), income (P0.01) and preoperative androgen-deprivation therapy (P = 0.039) significantly influenced the patients' decision on the purchase of the device. Relevant admission education achieved a 45% decrease in the number of the patients unwilling to accept penile rehabilitation for worrying about its negative effect on cancer treatment, a 25% decrease in those rejecting penile rehabilitation because of age, and a 20% decrease in those refusing it due to the tumor stage. The cost of treatment was an important reason for the patients' rejection of postoperative penile rehabilitation.The tumor stage and income are the main factors influencing PCa patients' decision on postoperative penile rehabilitation. Relevant admission education and reduced cost of rehabilitation are important for popularization of postoperative penile rehabilitation in PCa patients.

Alzheimer's disease (AD) is characterized by deficits in learning and memory abilities, as well as pathological changes of amyloid-β (Aβ) plaque and neurofibrillary tangle formation in the brain. Insulin has been identified as a modulator of the neuronal pathways involved in learning and memory, and is also implicated as a modulator of Aβ and tau metabolism. Disrupted insulin signaling pathways are evident in AD patients and it is understood that type 2 diabetes can increase the risk of developing AD, suggesting a possible link between metabolic disorders and neurodegeneration. SH2B1 is a key protein in the insulin signaling pathway involved in regulating the activity of the insulin receptor. To further identify the role of the insulin signaling pathway in the pathology of AD, SH2B (dSH2B homologue in flies) in neurons was partially knocked out or overexpressed in an AD Drosophila model expressing Aβ42. Partial knockout of neuronal SH2B in the Aβ42-expressing Drosophila had a detrimental effect on mobility and neurotransmission, and increased levels and intraneuronal accumulation of Aβ42, as assessed by ELISA and immunostaining. Alternatively, partial overexpression of neuronal SH2B in the Aβ42-expressing Drosophila improved lifespan, mobility, and neurotransmission, as well as decreased levels and intraneuronal accumulation of Aβ42. Thus, SH2B1 may be an upstream modulator of Aβ metabolism, acting to inhibit Aβ accumulation, and has a role in the pathogenesis of AD. SH2B1 may therefore have potential as a therapeutic target for this common form of dementia.

This study investigated the clinical activity of abiraterone plus prednisone in docetaxel-naive and docetaxel-resistant Chinese patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 146 patients with docetaxel-naive group (103 cases) and docetaxel-resistant group (43 cases) were enrolled from the Shanghai Cancer Center (Shanghai, China) in this retrospective cohort study. The efficacy endpoints were prostate-specific antigen response rate, prostate-specific antigen progression-free survival, clinical/radiographic progression-free survival, and overall survival in response to abiraterone plus prednisone. Significantly higher prostate-specific antigen response rate was found in docetaxel-naive group (54.4%, 56/103) compared to docetaxel-resistant group (34.9%, 15/43) (P = 0.047). In addition, significantly higher median prostate-specific antigen progression-free survival (14.0 vs 7.7 months, P = 0.005), clinical or radiographic progression-free survival (17.0 vs 12.5 months, P = 0.003), and overall survival (27.0 vs 18.0 months, P = 0.016) were found in docetaxel-naive group compared to docetaxel-resistant group, respectively. The univariate and multivariate analyses indicated that lower albumin and visceral metastases were independent significant predictors for shorter overall survival. To sum up, our data suggested that abiraterone plus prednisone was efficient in both docetaxel-naive and docetaxel-resistant Chinese patients. Moreover, higher PSA response rate and longer overall survival were observed in the docetaxel-naive group, which suggested that abiraterone was more effective for docetaxel- naive patients than for docetaxel failures.

Surgical excision is essential for management of the rare and aggressive neoplasm adrenal cortical carcinoma (ACC). Five-year overall survival (OS) after surgery for ACC is dependent on disease stage, but for all stages the risk of death declines with time after surgery. We calculated the effect of post-surgical duration on conditional survival (CS) among ACC patients. A total of 641 patients with M0 ACC were selected from the Surveillance, Epidemiology, and End Results (SEER) registry (1988-2012). OS for the entire cohort at 1, 2, 3, 4, 5 and 6 years was 81.4%, 66.8%, 56.3%, 50.3%, 47.2% and 44.3%, respectively. CS for an additional year given prior survival for 0, 1, 2, 3, 4 or 5 years was 81.4%, 81.1%, 83.0%, 87.5%, 93.4% and 93.4%, respectively. Age, tumor stage, tumor grade and marital status affected OS and CS. Increases in 1-year CS over time were more pronounced in patients with poorer prognostic factors. With longer follow-up, tumor stage- and grade-dependent differences in CS decreased or even disappeared. CS may provide more meaningful life expectancy predictions for survivors of ACC than conventional survival analysis.

// Da-Long Cao 1, 2 , Ding-Wei Ye 1, 2 , Bo Dai 1, 2 , Hai-Liang Zhang 1, 2 , Yi-Jun Shen 1, 2 , Yao Zhu 1, 2 , Yi-Ping Zhu 1, 2 , Guo-Hai Shi 1, 2 , Chun-Guang Ma 1, 2 , Wen-Jun Xiao 1, 2 , Xiao-Jian Qin 1, 2 , Guo-Wen Lin 1, 2 1 Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China Correspondence to: Ding-Wei Ye, e-mail: dwyeli@163.com Keywords: prostate cancer, susceptibility, polymorphism, glutathione S-transferases T1, glutathione S-transferases M1 Received: June 21, 2015 Accepted: September 14, 2015 Published: September 24, 2015 ABSTRACT Background: Genetic polymorphism was hypothesized to be reason of variation in prostate cancer incidence among different racial group. Based on that published data on the association of prostate cancer susceptibility with polymorphisms in genes encoding Glutathione S-transferases (GSTs) were inconclusive, the aim of this study was to more precisely address the role of GSTs polymorphisms (especially, GSTT1 and GSTM1 deletions) on prostate cancer risk in Asian descent. Methods: A meta-analysis including 8 articles with 711 cases and 1122 controls for GSTT1 and 1098 cases and 1588 controls for GSTM1 was performed. Results: Significantly increased prostate cancer risk was found among subjects carrying GSTM1 null genotype (odds ratio (OR) = 1.403; 95% confidence interval (CI) = 1.088 – 1.808) but not among subjects carrying GSTT1 deletion genotype (OR = 0.959; 95%CI = 0.709 – 1.297). When stratified by country, the null genotype of GSTT1 neither increased nor decreased prostate cancer risk significantly in China (OR = 1.355; 95%CI = 0.895 – 2.049), Japan (OR = 0.812; 95%CI = 0.545 – 1.211), and Korea (OR = 1.056; 95%CI = 0.727 – 1.534). While significant association of elevated prostate cancer risk with GSTM1 deletion were found in China (OR = 1.665; 95%CI = 1.324 – .094) and Korea (OR = 1.914; 95%CI = 1.311 – 2.793) but not in Japan (OR = 0.980; 95%CI = 0.726 – 1.321). Conclusion: In summary, this meta-analysis suggested that the null genotype of GSTM1 rather than GSTT1 may be involved in the etiology of prostate cancer in Asian population.

Estrogen is a crucial hormone for osteoclast inhibition and for preventing osteoporosis. However, the hormone's role in osteoblast growth and differentiation remains unclear. The complexity of estrogen's role in guiding osteoblast behavior arises partly from crosstalk with other signaling pathways, including Wnt signaling. In this study, we show that the Wnt agonist, LiCl, induced Fhl1 gene expression, which substantially enhanced osteoblast differentiation. Staining with alizarin red revealed that MC3T3-E1 mineralization was enhanced by overexpression of Fhl1. In addition, Fhl1 promoted the expression of the osteogenic markers, Runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and osteopontin (OPN), whereas MC3T3-E1 cells with gene knockdown of Fhl1 exhibited limited mineralization and expression of Runx2, OCN, and OPN. We further demonstrate evidences from quantitative reverse transcription real-time polymerase chain reaction and reporter assay that Fhl1 expression was synergistically stimulated by estrogen (E2) and LiCl, but reduced by the estrogen-receptor inhibitor fulvestrant (ICI 182,780). However, estrogen could not enhance osteogenesis while Fhl1 expression was knocked down. Because estrogen and Wnt signaling frequently interact in developmental processes, we propose that Fhl1 can be an acting molecule mediating both signaling pathways during osteogenesis.

// Yi-Ping Zhu 1,2,* , Fang-Ning Wan 1,2,* , Yi-Jun Shen 1,2 , Hong-Kai Wang 1,2 , Gui-Ming Zhang 1,2 and Ding-Wei Ye 1,2 1 Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Ding-Wei Ye, email: // Keywords : castration-resistant prostate cancer, COL6A1, reactive stroma, tumorigenesis Received : January 12, 2015 Accepted : March 01, 2015 Published : March 30, 2015 Abstract Castration-resistant prostate cancer (CRPC) remains the most critical challenge in the clinical management of prostate cancer (PCa). Reactive stromal changes in PCa are likely involved in the emergence of CRPC. In the present study, we identified a novel oncogene termed COL6A1 which was upregulated in the reactive stroma of CRPC. We established an androgen-independent LNCaP (LNCaP-AI) cell line in steroid-reduced (SR) medium within 2 months. We examined COL6A1 expression with western blot during the LNCaP-AI induction, and studied the function of COL6A1 in vitro and in vivo . Immunohistochemical staining of COL6A1 was performed in ten pairs of androgen-sensitive PCa and CRPC samples. We demonstrated that COL6A1 expression was markedly increased in LNCaP-AI cells and CRPC tissues compared with LNCaP cells and paired androgen-sensitive PCa specimens. In vitro , COL6A1 knockdown resulted in G1-S cell cycle arrest and descended vitality. Overexpression of COL6A1 was associated with accelerated S phase entry and elevated vitality in prostate cancer cells. COL6A1 also promoted tumorigenesis of LNCaP cells in vivo . Taken together, these data suggest an important role of COL6A1 in the molecular etiology of castration-resistant prostate cancer, and support the potential use of COL6A1 in CRPC therapy.

PBRM1 is a novel tumor suppressor gene that can inhibit cancer cell proliferation and predict the outcome of renal cell carcinoma (RCC), but its biological role needs further elucidation. We examined expression of the PBRM1 gene in RCC cell lines and the effect of PBRM1 on cell proliferation and cell cycle in RCC ACHN cells. Microarray processing and analysis was used to explore novel pathways involved in tumorigenesis related to PBRM1 knockdown. PBRM1 was expressed at high levels in RCC ACHN cells and lentivirus-mediated PBRM1 knockdown in these cells caused an increase in the proportion of cells in S phase of the cell cycle and promoted in vitro proliferation and migration. In vivo experiments showed that downregulation of PBRM1 promoted tumorigenesis in nude mice. In pathway gene chip analysis, the chemokine/chemokine receptor interaction pathway showed the greatest difference in gene expression upon PBRM1 knockdown. Protein levels of IL6ST and CCL2 were increased, whereas levels of interleukin (IL)-8, IL-6, and CXCL2 were decreased, in knockdown cells. Re-expression of IL-8 in PBRM1 knockdown ACHN cells could significantly decrease cell proliferation/migration and induced cell arrest in the G2/M phase. These findings indicate that PBRM1 alters cell cycle progression and inhibits proliferation and migration of ACHN cells through the chemokine/chemokine receptor pathway.

Controversial data on the association of single-nucleotide polymorphisms (SNPs, rs3787016GA and rs10773338GA) in long non-coding RNA (lncRNA) with prostate cancer risk were emerged. Considering possible genetic differences among populations, we conducted the present study to clarify these discrepancies and re-validate these results in an eastern Chinese population and thus provide clues for new therapeutic targets of prostate cancer.Genotypes of these two SNPs from 1015 ethnic Han Chinese patients with prostate cancer and 1032 cancer-free controls were determined by Taqman assays. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk associations.The association of rs3787016 A variant genotypes with a significantly higher prostate cancer risk were found (adjusted OR = 1.418, 95% CI = 1.090-1.844 for AA vs GG). Stratification analysis indicated that the risk of rs3787016 variant AG/AA genotypes was more evident in younger subjects, ever smoking, patients with Gleason score ⩾ 7(4+3) and highly aggressive status. All these risks were not present for rs10773338GA.These findings suggested that lncRNA SNPs may contribute to prostate cancer risk in an eastern Chinese population. Larger and well-designed studies with different ethnic populations are warranted to validate our findings.

Dicer and Argonaute2 (Ago2) are critical components responsible not only for RNA interference but also for microRNA synthesis. The present study investigated the roles of Dicer and Ago2 in prostate cancer (Pca). First, the expression levels of Dicer and Ago2 in Pca tissues were determined by immunohistochemistry (IHC) and compared with pathological features. Next, RNA interference was used to down-regulate the expression levels of Dicer and Ago2 in the Pca cell lines LNCaP, PC-3, and DU145, and effects on proliferation, apoptosis, and cell cycle were detected using the CCK-8 assay and flow cytometry, respectively. We found that Dicer and Ago2 expression levels in Pca tissues were higher than those in adjacent benign tissues and correlated with lower Gleason patterns, with the exception of Dicer expression in localized Pca. In vitro, silencing Dicer or Ago2 inhibited cell proliferation and induced apoptosis in LNCaP, PC-3, and DU145, as well as arrested the cell cycle at the G2/M phase in androgen-dependent LNCaP, or at S phase in the androgen-independent PC-3 and DU145. Altogether these findings suggest that Dicer and Ago2 play important roles in proliferation, apoptosis, and the cell cycle in Pca and might serve as both promising biomarkers for Pca progression and potential therapeutic targets.

Objective To investigate whether visceral obesity is associated with certain histological subtypes of renal cell carcinoma (RCC) in a multicentre Chinese cohort. Patients and Methods A kidney tumour database was created using three tertiary centres in China; 487 patients were enrolled presenting with localised RCC and complete computer tomography (CT)/magnetic resonance imaging (MRI) information. A single-slice CT image was used to measure the area of visceral and subcutaneous adipose tissues in each patient. Statistical methods were used to analyse clear-cell RCC (ccRCC) and non-clear-cell RCC (non-ccRCC) as they relate to visceral fat area (VFA) and other risk factors, such as age, gender, tumour size, diabetes, hypertension, total fat area (TFA) and body mass index (BMI). Results In all, 418 patients had a ccRCC subtype and 69 had a non-ccRCC subtype. For all the patients with RCC, the mean VFA was 102 cm2, while mean BMI was 24 kg/m2. The mean VFA was greater in ccRCC than non-ccRCC patients by 25 cm2. There were significant differences in the mean VFA and TFA between patients with ccRCC and those with non-ccRCC. Multivariate analysis showed that the presence of VFA was more important than the effects of BMI and Type 2 diabetes on pathology prediction. In patients with a normal BMI, those with a higher quartile of VFA were more likely to develop ccRCC than those with a low VFA. Conclusions Increased visceral fat was found to be associated with ccRCC and the significance of VFA outweighed the effects of BMI and Type 2 diabetes for the prediction of RCC pathology in multivariate analyses. As a result, VFA could constitute a primary explanation for the link between obesity and ccRCC.

The DOC-2/DAB2 interactive protein (DAB2IP) is a member of the Ras GTPase-activating protein family. It has been shown to be often downregulated and a poor prognostic factor in several human malignancies. In this study, we analyzed the clinicopathological features and outcomes of DAB2IP expression in 135 patients with urothelial carcinoma of the bladder (UCB) treated by radical cystectomy plus bilateral lymph node dissection, and evaluated the effect of DAB2IP knockdown in vitro using the MTT method, colony formation assay, cell cycle assay, and cell migration and invasive assay. We found low expression of DAB2IP was significantly associated with high pathological stage (P = 0.002), high pathological grade (P = 0.02), tumor size more than 3 cm (P = 0.04), and presence of histological variants (P = 0.01). DAB2IP was an independent prognostic factor of disease recurrence (hazard ratio, 2.67; P = 0.034) and cancer-specific survival (hazard ratio, 2.79; P = 0.038). Knockdown of DAB2IP could promote cell proliferation, migration, and invasion. Downregulation of DAB2IP could activate the ERK and Akt pathways and was correlated with the expression of epithelial-mesenchymal transition markers, such as E-cadherin and vimentin. In conclusion, downregulation of DAB2IP is associated with features of biologically aggressive UCB and results in cell proliferation, migration, and invasion of bladder cancer. DAB2IP may serve as a promising biomarker in patients with UCB treated by radical cystectomy and bilateral lymph node dissection.

Using a population-based cancer registry, Thuret et al. developed 3 nomograms for estimating cancer-specific mortality in men with penile squamous cell carcinoma. In the initial cohort, only 23.0% of the patients were treated with inguinal lymphadenectomy and had pN stage. To generalize the prediction models in clinical practice, we evaluated the performance of the 3 nomograms in a series of penile cancer patients who were treated with definitive surgery. Clinicopathologic information was obtained from 160 M0 penile cancer patients who underwent primary tumor excision and regional lymphadenectomy between 1990 and 2008. The predicted probabilities of cancer-specific mortality were calculated from 3 nomograms that were based on different disease stage definitions and tumor grade. Discrimination, calibration, and clinical usefulness were assessed to compare model performance. The discrimination ability was similar in nomograms using the TNM classification or American Joint Committee on Cancer staging (Harrell's concordance index = 0.817 and 0.832, respectively), whereas it was inferior for the Surveillance, Epidemiology and End Results staging (Harrell's concordance index = 0.728). Better agreement with the observed cancer-specific mortality was shown for the model consisting of TNM classification and tumor grade, which also achieved favorable clinical net benefit, with a threshold probability in the range of 0 to 42%. The nomogram consisting of TNM classification and tumor grading was shown to have better performance for predicting cancer-specific mortality in penile cancer patients who underwent definitive surgery. Our data support the integration of this model in decision-making and trial design.

Treatment options for patients with castration-resistant prostate cancer (CRPC) are limited. The purpose of our study was to investigate the safety and efficacy in terms of prostate-specific antigen (PSA) response of a low-dose oral combination of etoposide and prednisone in patients with CRPC. Thirty-nine patients with prostate cancer (median age, 77.9 years) with progressive disease after standard hormonal therapy were enrolled. Etoposide (25 mg, twice daily) and prednisone (5 mg, twice daily) were administered orally. Each cycle comprised 21 consecutive days of treatment followed by a 7-day drug holiday. All patients previously treated with an antiandrogen were required to undergo antiandrogen withdrawal prior to entry into the study. A total of 226 cycles were administered with a median of 6.7 cycles per patient (range, 1–18 cycles). Sixteen of 39 patients (41%) with elevated PSA levels at baseline achieved at least a 50% reduction in PSA levels. Median progression-free survival for all patients was 5.9 months (range, 1–17 months). No Grade 4 toxicities were observed. The predominant toxicities were mucositis, nausea, fatigue, and anemia in twelve, nine, eight, and seven patients, respectively. Hematologic toxicity was infrequent, with no episodes of febrile neutropenia. The combination of low-dose etoposide and prednisone is an efficacious and reasonably well-tolerated oral regimen in the treatment of elderly patients with CRPC. This regimen can be easily administered in an outpatient setting and does not require frequent patient visits.

Dysregulation of long noncoding RNAs (lncRNAs) has been regarded as a primary feature of several human cancers. However, the genome-wide expression and functional significance of lncRNAs in bladder cancer remains unclear. The aim of this study was to identify aberrantly expressed lncRNAs that may play an important role in contributing to bladder cancer pathogenesis. In this study, we described lncRNAs profiles in four pairs of human bladder cancer and matched normal bladder tissues by microarray. We finally determined 3,324 differentially expressed human lncRNAs and 2,120 differentially expressed mRNAs (≥2-fold change). A total of 110 lncRNAs were significantly differentially expressed between the tumor and the control groups (≥8-fold change). Four lncRNAs (TNXA, CTA-134P22.2, CTC-276P9.1 and KRT19P3) were selected for further confirmation of microarray results using quantitative PCR (qPCR), and a strong correlation was identified between the qPCR results and microarray data. We also observed that numerous lncRNA expression levels were significantly correlated with the expression of tens of protein coding genes by construction of the lncRNA-mRNA co-expression network. Kyoto Encyclopedia of Genes and Genomes annotation showed a significant association with p53, bladder cancer, cell cycle and propanoate metabolism pathway gene expression in the bladder cancer group compared with the normal tissue group, indicating that deregulated lncRNAs may act by regulating protein-coding genes in these pathways. We demonstrated the expression profiles of human lncRNAs in bladder cancer by microarray. We identified a collection of aberrantly expressed lncRNAs in bladder cancer compared with matched normal tissue. It is likely that these deregulated lncRNAs play a key or partial role in the development and/or progression of bladder cancer.

This article experimentally investigates the agglomeration mechanism of CO2 primary particles inside a tube. The results show that a complicated particle motion in the upper portion of the tube is responsible for the formation of large snow particles. The high speed and complicated motion of the snow particles inside the tube provide both the opportunities and time for the collision of particles, which implies that only particle deposition and re-entrainment cannot completely describe the phenomenon of particle agglomeration. The results also show the mechanisms of particle agglomeration inside a tube, which include primary particle agglomerate in jet vortexes, agglomerated particles flowing upward into the recirculation region, particle clusters growing in the recirculation flow, and finally particles being released with the jet flow. A minimum tube length (30 mm in this case) is needed to ensure the complete formation of the agglomeration mechanisms with recirculation flow, and thus the formation of con...

Based on the RFID technology, we developed an intelligent building access control and mornitoring system, with which you can effectively control access to the special zone, and monitor the people entering the restricted zone timely and accurately, and helpfully monitor and deal with abnormal situation. Instead of the passive monitoring and alarming in the traditional security system, this system uses the active control. Thus it will provide a more effective way for safety management of enterprises.

Radio Frequency Identification (RFID) is an automatic identification technology that can identify the objects at a distance.This paper presents the design of remote attenance system based RFID. The system is implemented for the automation of time and attenance using a new mode of barrer-free channel. With a simple setting, the attendance system is capable of recording real time attendance, counting attendance and attenance statistics analysis. Reports and charts will be provided for the top management to make decision, annual review, and planning on man power. The applied result of the system shows that it is simple and effective.

This research experimentally investigates influences of superheat on flashing spray characteristics and on the snow formation of liquid CO 2 . Results show that liquid, two-phase flow or even three-phase flow can be found upon the release of liquid CO 2 from high pressure to atmospheric pressure. This is due to complicated phase transition processes that involve hydrodynamic instabilities and thermal non-equilibrium conditions. Results also show that the spray pattern transfers from jet spray to cone spray, and then to a bowl spray configuration with the increase of superheat. The drastic changes in spray angle and mass flow rate indicate onset conditions from external-flashing to internal-flashing atomization mode. This is due to bursts of bubbles inside the nozzle chamber that result in the choking of the two-phase flow. Moreover, a few microns of CO 2 snow size are measured in this research, which is consistent with records from literature on this topic. The narrower size distribution of snow particles and a critical spray angle resulting from two competing phenomena under internal-flashing atomization mode are also discussed in this research.

Based on the results of TAX 327, a nomogram was developed to predict the overall survival of metastatic castration-resistant prostate cancer (mCRPC) after first-line chemotherapy. The nomogram, however, has not been validated in an independent dataset, especially in a series out of clinical trials. Thus, the objective of the current study was to validate the TAX 327 nomogram in a community setting in China. A total of 146 patients with mCRPC who received first-line chemotherapy (docetaxel or mitoxantrone) were identified. Because clinical trials are limited in mainland China, those patients did not receive investigational treatment after the failure of first-line chemotherapy. The predicted overall survival rate was calculated from the TAX 327 nomogram. The validity of the model was assessed with discrimination, calibration and decision curve analysis. The median survival of the cohort was 21 months (docetaxel) and 19 months (mitoxantrone) at last follow-up. The predictive c-index of the TAX 327 nomogram was 0.66 (95% CI: 0.54–0.70). The calibration plot demonstrated that the 2-year survival rate was underestimated by the nomogram. Decision curve analysis showed a net benefit of the nomogram at a threshold probability greater than 30%. In conclusion, the present validation study did not confirm the predictive value of the TAX 327 nomogram in a contemporary community series of men in China, and further studies with a large sample size to develop or validate nomograms for predicting survival and selecting therapies in advanced prostate cancer are necessary.

Objectives To determine whether carbonic anhydrase IX (CA IX) has prognostic value of lymph node metastases and cancer-specific survival in penile squamous cell carcinoma treated with surgery. Materials and methods CA IX expression was detected in the primary disease of 73 penile cancer patients using the method of immunohistochemistry. The expression levels of CA IX were categorized into 2 groups according to the cutoff of 10% of positively stained tumor cells. Associations between CA IX expression and clinicopathologic characteristics, immunoreactivity of p53 and Ki-67, and outcomes were analyzed. Results High CA IX expression was observed in 31 (42.5%) of cases. CA IX expression was not associated with patient age, T stage, grade, lymphovascular invasion, and Ki-67 expression, but was associated with p53 expression ( P = 0.015). Both univariate and multivariate analysis failed to show CA IX expression was a statistically significant predictor of lymph node metastases and cancer-specific survival. Conclusions Immunohistochemical expression of CA IX did not associate with lymph node metastases and cancer-specific survival in penile squamous cell carcinoma. A panel of prognostic markers that reflect the characteristic of tumor cell and organ microenvironment may be more suitable for prognostication in penile cancer.

With the development of the technology of mobile communication, smartphones have become one of the most popular ways that people get information. However some restrictions such as the screen size, ambient brightness etc. still cause some troubles to read news by smartphones. We based on Android designed an audio news software system by means of the speech synthesis technology which can afford pleasure to listen to information. Using the Andriod technology we developed the smartphone client software which can get the latest information in RSS channels by communicating with the server. Also, it can dynamically manage the RSS channels subscribed by yourself. In the design, we used the techniques of the Android UI framework and component which made the smartphone interface succinct and easy. In order to improve data store efficiency we implemented the data modification and store by transforming between the Json format and the Java object. Based on the iFLY mobile speech platform we developed the audio news player. The function of information automatic acquisition in the server made it possible that smartphones can get the latest information of the subscription channels.

The aim of the present study was to investigate the effects of Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA) on inhibiting the proliferation of bladder cancer cell lines and to further define its functional mechanisms. T24 and 5637 cells were treated with PA-MSHA at various concentrations and times. Cell proliferation was analyzed using Cell Counting Kit-8 (CCK-8) assays. The cell cycle distribution and apoptosis induced by PA-MSHA were measured by flow cytometry with propidium iodide (PI) and annexin V-fluorescein isothiocyanate (FITC) staining. Western blotting was used to evaluate the expression levels of the apoptosis-related molecules and PI3K-AKT-mTOR signaling pathway proteins. A time- and concentration-dependent cytotoxic effect of PA-MSHA was observed in the T24 and 5637 cells. Flow cytometry with PI and annexin V-FITC staining showed that the various concentrations of PA-MSHA were all able to induce the apoptosis and G0-G1 cell cycle arrest of the bladder cancer cells. Cleaved caspase-8 and -9 and Fas protein expression levels were markedly associated with an increase in the apoptosis of the bladder cancer cells. The cells stimulated with PA-MSHA also exhibited a downregulation of PI3K-AKT-mTOR signaling. PA-MSHA inhibits proliferation and induces apoptosis in the T24 and 5637 bladder cancer cell lines by modulating caspase family proteins and affecting the cell cycle regulation machinery. The PI3K-AKT-mTOR signaling pathway may be important in the direct anticancer cytotoxic effect of PA-MSHA.

Accurate assessment of disease characteristics is a prerequisite for treatment decision making regarding small renal masses. In this study we evaluate the association between visceral obesity and Fuhrman grade in patients with cT1a renal cell carcinoma.We retrospectively collected data on 186 patients with surgically treated cT1a renal cell carcinoma. Single slice computerized tomography was used to measure the area of visceral and subcutaneous adipose tissue. Visceral obesity was calculated as the proportion of visceral adipose tissue to overall adipose tissue. Other analyzed factors included clinical characteristics (age, gender, body mass index and tumor size) and anatomical features of the tumor defined by the R.E.N.A.L. nephrometry score. The association between predictors and high grade disease (Fuhrman grade III or IV) were assessed using logistic regression analyses.A total of 47 (25.3%) tumors were classified as high grade. The percentage of visceral adipose tissue was higher in male participants but did not correlate with body mass index, age or tumor size. In univariate analyses the percentage of visceral adipose tissue and tumor size were significantly associated with higher Fuhrman grade. Multivariate analysis showed that the percentage of visceral adipose tissue (OR 1.06, p = 0.0018) and tumor size (OR 1.91, p = 0.047) were independent predictors of high grade cancer. Addition of the percentage of visceral adipose tissue to a model including clinical characteristics and anatomical features of the tumor remarkably improved its discriminatory ability (p = 0.0010).Increased visceral obesity was found to be strongly associated with higher Fuhrman grade in patients with cT1a renal cell carcinoma. Further studies are needed to confirm these findings and discover the underlying biological mechanism.

© 2 0 1 2 T H E A U T H O R S B J U I N T E R N A T I O N A L © 2 0 1 2 B J U I N T E R N A T I O N A L | 11 0 , E 11 2 1 – E 11 2 4 | doi:10.1111/j.1464-410X.2012.11491.x E 11 2 1 What ’ s known on the subject? and What does the study add? Both the treatment and reconstruction after resection of penoscrotal extramammary Paget ’ s disease (EMPD) are of concern among oncological urologists. Reconstruction of large skin defects after wide local resection of this disease remains challenging and skilled work.

This paper investigates the production of CO2 snow by flash-atomization of liquid carbon dioxide for material cleaning process. The evolution of flash-atomization processes was recorded by means of high-speed shadowgraph. Results shows that the degree of superheat condition of liquid CO2 greatly influence the atomization modes, bobbles growth rate and concentration, and thus result in difference spray angle, spray pattern, and the structure of liquid jet which is suitable for different material cleaning applications. It is found that the spray angle first slowly increases with increase in the degree of superheat (ΔT) under external flash atomization processes. It is increased drastically as the spray transform from external-flashing to internal-flashing mode. Finally the spray angle is decreased again because of the decrease of mass flowrate due to the internal flashing processes . Moreover, the spray angle is increased as the length-to-diameter ratio (L/D) is increased. This is due to the higher bobble growth rate in terms of different pressure distribution and bobble growth time. It is also found that the external-flashing disappears at higher L/D because of the heat transfer to the liquid carbon dioxide. It is concluded that the superheated condition is useful in the control of the spray angle for material cleaning processes.

Several prediction models have been developed to estimate the outcomes of prostate biopsies. Most of these tools were designed for use with Western populations and have not been validated across different ethnic groups. Therefore, we evaluated the predictive value of the Prostate Cancer Prevention Trial (PCPT) and the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculators in a Chinese cohort. Clinicopathological information was obtained from 495 Chinese men who had undergone extended prostate biopsies between January 2009 and March 2011. The estimated probabilities of prostate cancer and high-grade disease (Gleason6) were calculated using the PCPT and ERSPC risk calculators. Overall measures, discrimination, calibration and clinical usefulness were assessed for the model evaluation. Of these patients, 28.7% were diagnosed with prostate cancer and 19.4% had high-grade disease. Compared to the PCPT model and the prostate-specific antigen (PSA) threshold of 4 ng ml(-1), the ERSPC risk calculator exhibited better discriminative ability for predicting positive biopsies and high-grade disease (the area under the curve was 0.831 and 0.852, respectively, P0.01 for both). Decision curve analysis also suggested the favourable clinical utility of the ERSPC calculator in the validation dataset. Both prediction models demonstrated miscalibration: the risk of prostate cancer and high-grade disease was overestimated by approximately 20% for a wide range of predicted probabilities. In conclusion, the ERSPC risk calculator outperformed both the PCPT model and the PSA threshold of 4 ng ml(-1) in predicting prostate cancer and high-grade disease in Chinese patients. However, the prediction tools derived from Western men significantly overestimated the probability of prostate cancer and high-grade disease compared to the outcomes of biopsies in a Chinese cohort.

To investigate the oncologic influence of transurethral resection of the prostate (TURP) as a cytoreductive surgery in metastatic hormone sensitive prostate cancer (mHSPC), in the setting of continuous complete androgen blockade (CAB).Medical histories of 146 consecutive Chinese males with newly diagnosed mHSPC, registered in our institution in 2006 and 2007, were reviewed. All of these patients received CAB as initial systematic therapy. Demographics and cancer control outcomes from 39 mHSPC patients who underwent TURP for a relief of bladder outlet obstruction were compared with those of the other 107 who received CAB only when they were still hormone-sensitive. Median follow-up was 15 months (3 to 27 months).Age at diagnosis, baseline PSA, and biopsy Gleason score were comparable between the 2 groups. Patients who underwent a TURP had lower PSA nadir (median 0.15 ng/ml vs. 0.82 ng/ml, P = 0.015) and longer time to PSA nadir (11.2 months vs. 6.4 months, P0.001). More patients in the non-TURP group developed hormone refractory prostate cancer (P = 0.007). The TURP group had a tendency towards longer disease-specific survival and overall survival (24.4 months vs. 24.1 months and 24.4 months vs. 22.9 months, respectively), though this did not reach statistical significance.TURP resulted in a better and more prolonged response to hormone therapy in mHSPC, with a trend towards positive influence in disease specific survival and overall survival. To date, our preliminary report is the first study regarding long-term survival of cytoreductive surgery in mHSPC, and further investigations are warranted.

This paper describes the characteristics of CO 2 snow formation with co-axial type injection systems. The injection of CO 2 snow flow is controlled by a co-axial type nitrogen auxiliary nozzle. Five cases of co-axial nitrogen nozzle with different diameters and injection types of auxiliary nitrogen are presented. Flow field visualization and spray characteristics are performed by the particle image velocimetry (PIV). Result shows that the CO 2 snow particles would collide with each other and generate lager particles in the recirculation zone of the formation chamber. Results also show that the particle size distribution is influenced by the geometry of the injection device. The length of the formation chamber influence the region and strength of recirculation flow. In the region after reattach zone of recirculation flow, the fine particles deposit on the chamber wall and form a deposition layer. The particles in the main stream further impinge onto the deposition layer and result in the snowballs. It turns out that the mean particle size becomes larger as the length of chamber is increased. Results also show that CO 2 snow jet has higher velocity and the flow-focusing takes place with nitrogen auxiliary gas. Furthermore, the mist layer of the jet flow caused by lower temperature of CO 2 snow is eliminated when co-axial nitrogen flow is injected. The velocity of CO 2 snow jet is increased under higher injection pressure of co-axial nitrogen flow. Furthermore, smaller diameter of nitrogen auxiliary nozzle results in higher injection velocity of CO 2 snow jet. Hence the injection power of the CO 2 snow jet can be controlled by the design of the nitrogen auxiliary nozzle. It will be useful in the medical applications of cryotherapy treatment and the dry cleaning of the semiconductor and solar cell manufacturing processes.

Background: Penile metastases from primary bladder cancer are extremely rare. Case Report: The medical records of 8 patients who presented with metastatic penile carcinoma originating from bladder between 2002 and 2010 were analyzed. The main complaint was a painless nodule (6 cases), priapism (1 case), and penile pain (1 case). All of the penile metastases were metachronous. The interval between primary cancer and penile metastases ranged from 1 to 100 months (mean 26.4 months). Total penectomy combined with systemic chemotherapy was the treatment of choice in 4 cases. 1 patient only accepted external beam radiotherapy, and 3 patients only accepted chemotherapy due to disseminated disease. The time interval between penile metastases and death ranged from 4 to 23 months (mean 11.4 months). Conclusion: Penile metastases secondary to primary bladder cancer are rare and represent a challenging problem. The common mode of spread to the penis is by retrograde venous route. The overall outcome is very poor, and most patients will die within 1 year despite systemic chemotherapy and supportive care. Radical ablative surgery is justified only for symptomatic relief.

It has been suggested that pancreatic cancer is associated with a greater prevalence of depression than many other cancers, but the mechanism accounting for this potential association has not yet been illustrated. In the present study, conditioned media (CM) from three pancreatic cancer cell lines and primary pancreatic cancer cells from two patients were added to culture system of differentiated pheochromocytoma cell line PC12. The release of dopamine (DA) and norepinephrine (NE) by PC12 was significantly inhibited after CM treatment (P

We investigated whether narrow-band imaging (NBI) was superior to white light imaging (WLI) for detecting primary non-muscle invasive bladder cancer (NMIBC) in a randomized imaging sequence modality, as the increased detection rate by NBI maybe result from the "second look" inspection of the bladder.Between February 2009 and May 2010, NBI and WLI flexible cystoscopy were prospectively performed on 78 patients with primary suspected NMIBC. According to randomization protocol, the bladder was mapped using WLI then NBI or vice versa within the same observation time. Suspicious lesions together with controlled normal-appearing mucosa were biopsied and examined by a pathologist blinded to the imaging sequence. The tumors detected on patient and tumor level, sensitivity, specificity, and accuracy were compared in both imaging.Sixty-nine of 78 (88.5%) patients were diagnosed with bladder cancer including 211 tumors totally. Of these, 36 (17.1%) tumors in 13 patients were detected by NBI only, while 4 (1.9%) tumors in 3 patients found by WLI only. NBI identified significantly more additional tumors than WLI (P0.01). The sensitivity of WLI versus NBI for detecting primary bladder tumors was 77.7 versus 92.9% (P0.0001), the specificity 82.7 versus 73.5% (P0.05), and the accuracy 79.3 versus 86.7% (P0.05). The sensitivity of WLI versus NBI for detecting carcinoma in situ (CIS) was 68.3 versus 87.8% (P0.05), the specificity 82.9 versus 77.1% (P0.05), and the accuracy 75 versus 82.9% (P0.05).The "second look" did not compromise the superiority of NBI over standard WLI flexible cystoscopy for detecting primary NMIBC including CIS lesions.

Objectives: Previous prognostic factor models for metastatic renal cell carcinoma (mRCC) have not included erythrocyte sedimentation rate (ESR). We designed the present study to evaluate the prognostic value of ESR for mRCC patients treated with sorafenib. Methods: Sorafenib was given to 83 patients with clear cell mRCC. Serum ESR was tested before treatment and every 4 weeks after first administration of sorafenib. Oncological evaluation was carried out every 8 weeks. Analyzed factors included age, sex, performance status, method of nephrectomy, number of metastatic organs, anemia, lactate dehydrogenase, corrected calcium, albumin, baseline ESR level and ESR kinetics status. Kaplan–Meier and Cox regression analyses on progression-free survival (PFS) were carried out. Results: Baseline ESR levels ranged from 3 to 154 mm/h, and 43 (41.0%) patients had an ESR level higher than 40 mm/h. Median PFS was 10.0 months (95% CI 7.6–12.4 months). Dividing the cohort into three groups according to ESR kinetics status, median PFS was 27 months in the decreased ESR group, 12 months in the stable ESR group and 6 months in the increased ESR group. Performance status, time from diagnoses to sorafenib treatment, number of metastatic organs and ESR kinetics were independent predictors for PFS in multivariable Cox regression model analysis, with an area under the curve of 0.865 in a binary logistic regression model of 12-month PFS probability. Conclusions: ESR kinetics can be useful to monitor the treatment response and to predict PFS for mRCC patients treated with sorafenib as second-line therapy.

BACKGROUND miR-21 has been recognized as an “onco-microRNA” with the activity of negatively modulating the expression of tumor-suppressor genes. However, its role in prostate cancer (CaP) has not been well-documented. We designed this study to assess the potential function of serum miR-21 in the progression of CaP. METHODS Serum samples of 56 patients, including 20 patients with localized CaP, 20 with androgen-dependent prostate cancer (ADPC), 10 with hormone-refractory prostate cancer (HRPC), and 6 with benign prostatic hyperplasia (BPH), were collected for the measurement of miR-21. The 10 HRPC patients were administered docetaxel-based chemotherapy. Quantification of miR-21 was assayed by specific TaqMan qRT-PCR. RESULTS Serum miR-21 level was found to correlate to serum PSA level in patients with ADPC and HRPC, P = 0.012 and 0.049, respectively. There was no significant difference in serum miR-21 level between BPH, localized CaP and ADPC with PSA level 4 ng/ml. Six of the 10 HRPC patients reached partial remission with a decreased PSA level of >50% after chemotherapy. Serum miR-21 levels were higher in patients who were resistant to docetaxel-based chemotherapy when compared to those sensitive to chemotherapy, P = 0.032. CONCLUSIONS Serum miR-21 levels are elevated in HRPC patients, especially in those resistant to docetaxel-based chemotherapy. It may be applicable as a marker to indicate the transformation to hormone refractory disease, and a potential predictor for the efficacy of docetaxel-based chemotherapy. Prostate 71:326–331, 2011. © 2010 Wiley-Liss, Inc.

Optimal management for penile cancer in patients with clinically negative lymph nodes is still under debate. We developed and evaluated a nomogram to stratify patients who are suitable candidates for further treatment.This study included 110 men with penile cancer and clinically negative lymph nodes from 1990 to 2008. All patients underwent primary tumor resection and regional lymphadenectomy. We retrospectively reviewed medical records and tumor slides. Statistical analysis was done in R with library rms.The lymph node metastasis rate in the entire cohort was 23.6%. The final model, presented as a nomogram, included T stage, grade, lymphovascular invasion and p53 expression. Only lymphovascular invasion showed independent prognostic value on multivariate analysis (p = 0.024). The model also showed good calibration (bootstrap corrected concordance index 0.79). To determine the clinical usefulness of the nomogram we compared it with the European Association of Urology risk classification using decision curve analysis. At a 10% probability threshold our nomogram led to 1 positive result per 100 patients without an increase in the number of false-positive results. At this probability threshold the model also decreased 13 unnecessary interventions per 100 patients without missing more metastatic disease.We generated a nomogram in patients with clinically node negative penile cancer based on readily available pathological factors. The clinical usefulness of the nomogram was evidenced by decision curve analysis.

To investigate whether microRNA-21 was involved in mediating the chemoresistance of prostate cancer cells to docetaxel. A microarray technique was used to determine the miRNA profile in docetaxel-resistant PC3 cells. Real-time PCR was used to confirm the array results. miR-21 mimics and inhibitors were synthesized and introduced to cells using Lipofectamine 2000. Cell proliferation was examined with the CCK-8 assay. Luciferase reporter containing PDCD 3′UTR was constructed and the activity was detected by a dual luciferase assay. PDCD4 protein expression was evaluated using Western blot. A docetaxel-resistant prostate cancer PC3 cell line (PC3R) was established . Using microarrays, miR-21 was found to be up-regulated in PC3R cells. Ectopic expression of miR-21 increased the resistance to docetaxel in PC3 wild type cells. In contrast, silencing of miR-21 in PC3R cells sensitized the cells to docetaxel. The IC50 values for miR-21-silencing cells and control cells were 28.31 and 35.89 nmol/L, respectively. PDCD4, a direct target gene of miR-21, could mediate chemoresistance to docetaxel in PC3 cells. Our findings suggest that miR-21 contributed to the resistance of PC3 cells to docetaxel, and that targeting miR-21 may offer a promising therapeutic approach in sensitizing prostate cancer to docetaxel treatment.

This paper investigates the characteristics of a piezoelectric micro-injector for drop-on-demand (DOD) applications. The micro-injector is designed with an inner block inside the chamber to enhance the instability energy for the production of mono-size droplet. The micro-nozzle was fabricated by MEMS processes. The upper chip is a silicon chip with two holes as the inlet and outlet of the liquid matter. A diaphragm is mounted on the center of the upper chip. The lower chip has an orifice of 50µm in diameter. The flow through the chamber is used to promote the refilling mechanism for droplet generation. A piezoelectric actuator operated in push mode (D33) was mounted on the upper chip to drive the liquid through the nozzle. An inner block is designed on the inner side of the upper chip. Results show that the micro-injector with inner block could generate mono-size droplet under the driving voltage ranging from 62.5 to 150 volt at frequency of 3.2 kHz. The droplets size was 60µm with velocity ranging from 3.3 to 4.7 m/s which is higher than the case without inner block. As a comparison, the injection of the micro-injector without inner block needs a much higher driving voltage of 112.5 volt at driving frequency of 9.7kHz. It is concluded that the micro-injector with the inner block performs better than the one without the inner block.

We investigated the potential value of prostate-specific antigen half-life (PSAHL) and decreasing velocity (PSAVd) to predict progression-free survival (PFS) and overall survival (OS) in Chinese patients with prostate cancer. A total of 153 patients treated with hormonal therapy were included in the study. Of these, 78 patients progressed to hormone-refractory prostate cancer (HRPC) and 24 patients died by the end of follow-up. PSAHL was defined as the time during which prostate-specific antigen (PSA) concentration became half of the initial value during the first hormonal therapy. PSAVd reflected the decreasing velocity of PSA during the first hormonal therapy. PFS was defined as the interval from the beginning of hormonal therapy to HRPC. Cox proportional hazards regression analysis was used to evaluate whether PSAHL and PSAVd were significantly associated with PFS and OS. The median PSAHL and PSAVd were 0.50 months and 33.8 ng mL(-1) per month. The median PFS and OS were 22.7 months (95% confidence interval [CI], 22.0-29.6 months) and 43.5 months (95% CI, 37.9-48.4 months), respectively. On univariate and multivariate analysis, long PSAHL (> 0.5 months), metastatic disease, high biopsy Gleason scores (>or= 8) and high nadir PSA (> 0.4 ng mL(-1)) were all found to be significantly associated with short PFS. Long PSAHL, high nadir PSA and short PSA doubling time (PSADT