Screening for the Key Proteins Associated with Rete Testis Invasion in Clinical Stage I Seminoma via Label-Free Quantitative Mass Spectrometry.

Rete testis invasion (RTI) is an unfavourable prognostic factor for the risk of relapse in clinical stage I (CS I) seminoma patients. Notably, no evidence of difference in the proteome of RTI-positive vs. -negative CS I seminomas has been reported yet. Here, a quantitative proteomic approach was used to investigate RTI-associated proteins. 64 proteins were differentially expressed in RTI-positive compared to -negative CS I seminomas. Of them, 14-3-3γ, ezrin, filamin A, Parkinsonism-associated deglycase 7 (PARK7), vimentin and vinculin, were validated in CS I seminoma patient cohort. As shown by multivariate analysis controlling for clinical confounders, PARK7 and filamin A expression lowered the risk of RTI, while 14-3-3γ expression increased it. Therefore, we suggest that in real clinical biopsy specimens, the expression level of these proteins may reflect prognosis in CS I seminoma patients.

Relation between testosterone levels and body composition, physical functioning and selected biochemical parameters in adult males.

INTRODUCTION: The objective of the study was to examine the relationship between the values of selected parameters of physical function, body composition, body mass index (BMI) and biochemical markers of metabolic health with the total testosterone (TT) levels in adult males. We aimed to analyse the correlation between these values and variations in the TT levels. METHODS: A total of 17 subjects (age = 50.2 ± 8.1 years, TT = 11.4 ± 3.8nmol/l) were included in the study. Subjects were tested on physical function (1RM on leg press, bench-press, handgrip, VO2max), body composition (DXA), biochemical parameters (morning fasting blood samples). RESULTS: TT was inversely correlated with abdominal circumference (AC) (p.

Expression of E-cadherin, Ki-67, and p53 in urinary bladder cancer in relation to progression, survival, and recurrence.

Although the incidence varies with age and gender, urothelial bladder cancer is a relatively frequently occurring malignancy with variable clinical behavior that often has high recurrence rates. In this study, we analyzed the tumor tissues of 224 patients with pTa, pT1, and pT2 urinary bladder cancer. We performed a histomorphologic analysis and immunohistochemistry for p53, Ki-67, and E-cadherin, which were selected as markers of the malignant process. For pTa and pT1, univariate analyses of cancer-specific survival (CSS), progression-free survival (PFS), and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method, the log-rank test and Cox regression. Multivariate analysis was performed by a Cox regression analysis. Ki-67 (P<0.001) was significantly associated with CSS, but the highest association was shown for E-cadherin (P<0.001). For pT1 and pTa, the Kaplan-Meier analysis and the log-rank test revealed significantly worse PFS for patients with higher levels of Ki-67 (P<0.001) and lower levels of E-cadherin (P<0.001). Based on these obtained results, it can be clearly stated that Ki-67 and E-cadherin expression levels are associated with CSS, PFS and RFS. The clinical utility of these markers is valuable for pTa and pT1 urinary bladder cancer and should be further verified with prospective multi-center trials.

Advanced Reconstruction of Vesicourethral Support (ARVUS) during robot-assisted radical prostatectomy: first independent evaluation and review of other factors influencing 1 year continence outcomes.

PURPOSE: Anterior and posterior reconstructions of pelvic structures are used during a robot-assisted radical prostatectomy to obtain better continence outcomes. This study was conducted to evaluate the Advanced Reconstruction of Vesicourethral Support (ARVUS), a novel postprostatectomy reconstruction technique. METHODS: The study was designed as a prospective, controlled, partially randomized and blinded experiment. The statistical analysis was based on the generalized linear modeling (GLM) framework with random effects: the logit link was used to model the probability of achieving continence and the logarithmic link was used to evaluate the overall score of the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). The significance of the fixed effects and all possible two-way interactions was tested using the critical level of 0.05. RESULTS: The probability of achieving the continence significantly depends on the neurovascular bundle sparing (p < 0.001) and the time after the surgery (p < 0.001). Analogously, the expected ICIQ-SF score significantly depends on the nerve-sparing status (p = 0.035) and the time after the surgery (p < 0.001). No statistically significant difference between the unilateral or bilateral nerve sparing was found. The ARVUS technique seems to perform slightly worse with respect to the expected continence, but this difference is within the margins of random fluctuations (p = 0.715). CONCLUSIONS: The study demonstrates a significant positive association between the nerve-sparing approach and the patient's continence, however, regardless of the unilateral or bilateral approach. In terms of the continence rate, no statistically significant benefits of ARVUS were observed.

Strength training as a supplemental therapy for androgen deficiency of the aging male (ADAM): study protocol for a three-arm clinical trial.

INTRODUCTION: Androgen deficiency of the ageing male is a clinical syndrome resulting from the low production of androgens (testosterone levels <6.9 nmol/L) with symptoms including decline in lean mass, muscle strength, increases in body mass and overall fat mass. The aim of the study is to examine the effect of a 12 week strength training intervention on body composition, physical function, muscle cellular and molecular and selected biochemical markers of metabolic health in hypogonadal patients. METHODS AND ANALYSIS: The study is three-group controlled 12-week experiment to assess the effect of strength training on hypogonadal patients with testosterone replacement therapy and newly diagnosed males without testosterone replacement therapy. Age matched healthy eugonadal males are also engaged in strength training. Lean mass is used to determine sample size indicating, that 22 subjects per group will be sufficient to detect intervention related changes at the power of 0.90. All outcomes are collected before the intervention (pre-intervention assessments) and after the intervention (post-intervention assessments). Clinical outcomes are body composition (lean mass, fat mass and total body mass) measured by dual-energy X-ray absorptiometry, physical functioning assessed by physical tests and psychosocial functioning. The most important haematological and biochemical parameters included are glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, testosterone, luteinizing hormone, follicle-stimulating hormone, sexhormone-binding globulin, insulin and prostate-specific antigen. Muscle cellular and molecular outcomes are muscle fibre size and regulators of muscle fibre size. Muscle cellular outcomes are measured from muscle biopsies obtained from musculus vastus lateralis. ETHICS AND DISSEMINATION: This trial is approved by Ethics Committee of the University Hospital in Bratislava, Slovakia, (ref. trial number: 127/2017) and all subjects will be fully informed on the rationale, risks and benefits of the study and sign the written informed consent prior to entering the study. Results will be published in peer-reviewed journals and presented in scientific conferences. TRIAL REGISTRATION NUMBER: NCT03282682.

Patient's and physician's behavior on the management of benign prostatic hyperplasia among the patients at the risk of clinical progression. A multicenter noninterventional trial in Slovakia by "Prostate and Expectations of Treatment: Epidemiology Research" (PETER) study group.

OBJECTIVES: The aim of the survey was to assess physician's behavior and the global knowledge about patient's preferences and their psychological burden linked to lower urinary tract symptoms (LUTS) in an outpatient setting in Slovakia. METHODS: The study included 36 outpatient urological clinics. Overall, 1132 newly diagnosed LUTS patients were screened within 1 month. A total of 454 questionnaires were obtained from 459 LUTS patients with risk of progression (RP). Inclusion criteria were: age > 50 years, IPSS > 8, prostate volume ≥ 30 cm3, and PSA ≥ 1.5 to ≤ 10 ng/ml. RESULTS: The digital rectal examination, PSA testing, and urinalysis were used in all the centers as first visit examinations. The least frequently performed diagnostic procedure was uroflowmetry (74 %). The physician's preferred therapy for patients with RP was standard combined treatment in (52.6 %); followed by α-blocker alone (45 %) and monotherapy with 5-α-reductase inhibitors (5-ARI) only in 3 % of all asked urologists. Patient's mean age was 63.3 years (SD ± 7.4); baseline PSA value 2.2 ng/ml (SD + 3.2); prostate volume was 38.0 ml (SD ± 16.7 ml); Qmax was 11.5 ml/s (SD ± 4.6); and IPSS score 12.5 (SD ± 6.3). The most bothersome symptoms were nocturia (prevalence of ≥ 75 %), weak urinary stream (61 %), and retarded voiding (43 %). Patient's expectations of treatment were rapid improvement of symptoms (36.0 %), stabilization of symptoms (35.5 %), and reduction of potential risk of surgical intervention (25.8 %). CONCLUSIONS: Our research reflects the physician's behavior, patient's self-perception of the disease and therapeutic priorities in the current outpatient practice in Slovakia.

Patient's behavior and attitudes toward the management of benign prostatic hyperplasia among patients with the risk of disease progression: prospective study by "Prostate and Expectations of Treatment Epidemiology Research (PETER) study group".

BACKGROUND: The aim of the study was to evaluate patients attitudes with benign prostatic hyperplasia at the risk of progression during a 12-month period of observation. MATERIALS AND METHODS: A total of 426 patients from 45 outpatients centers were included and prospectively followed. Inclusion criteria were: age > 50 years, International Prostate Symptom Score (IPSS) > 8, prostate volume > 30 cm(3) (transabdominal ultrasound) and PSA > 1.5 to < 10 ng/ml. RESULTS: In all, 28.6% patients were naive, 62.9% used monotherapy (alpha-blocker), and 8.5% combined treatment (alpha-blocker/5alpha-reductase inhibitor/dutasteride). The most bothersome symptoms were the weak urine stream (60.8%) and nocturia (59.2%). Patients expectations from the treatment were stabilization of the disease and reducing the risk of surgery rather than rapid resolution of symptoms. Despite the presence of symptoms, 2.3% patients claimed that benign prostatic hyperplasia/lower urinary tract symptoms had no impact on their quality of life (QoL), in 48.1 % only little impact on QoL, and 47.9% patients percepted their symptoms as severe. Out of 71.4% patients treated previously, 26.5% patients were indecisive about the satisfaction of present treatment. Visual analog score was percepted more optimistically rather than the IPSS. Pearson's correlation r = 0.68 at the beginning and r = 0.83 at the end of the study. CONCLUSIONS: Prostate and Expectations of Treatment Epidemiology Research study highlights and reflects on patients behavior and self-perception, patients self-perception of the disease and therapeutic priorities during the 1 year of observation.

The relationship between renal cell carcinoma and nuclear retinoid/rexinoid receptors.

BACKGROUND: Renal cell carcinoma (RCC) is a urologic malignancy with a steady rise in incidence and high mortality rate. Between 60 to 70% of patients with renal cell carcinoma can only be cured with surgery but despite advances in early diagnostis, in around 20-30% of cases there is metastasis. For these patients, chemotherapy and radiotherapy are ineffective and hence the prognosis is poor. Retinoids are biologically active compounds of either natural or synthetic origin that are involved in complex physiological and developmental processes in many tissues including cell proliferation and activation of tumour suppression genes. This article reviews the role of retinoids and their cognate nuclear retinoid/rexinoid receptors in relation to renal cell carcinoma. METHODS: A literature search using ScienceDirect and Medline with a focus on the relationship between renal cell carcinoma and nuclear retinoid/rexinoid receptors. RESULTS: Use of retinoids/rexinoids in the treatment of locally advanced and metastatic RCC significantly prolongs median time of tumour progression and overall survival of patients. Combination therapy with other preparations has greater efficacy than treatment with retinoids alone. Patient survival can be predicted on the basis of the expression of different all-trans retinoic acid receptor (RAR) and 9-cis retinoic acid receptor (RXR) subtypes. CONCLUSIONS: Since nuclear retinoid receptors play a crucial role as ligand-activated, DNA binding, trans-acting, transcription-modulating proteins involved in a general molecular mechanism responsible for transcriptional responses in target genes, retinoids might be an alternative approach for the treatment of renal cell carcinoma.

Carbonic anhydrase IX is a clinically significant tissue and serum biomarker associated with renal cell carcinoma.

Carbonic anhydrase IX (CA IX) is regarded as one of the most prominent markers of tumor hypoxia with potential to serve as a diagnostic biomarker, prognostic indicator as well as tumor therapeutic target. The aim of the present study was to perform an in-depth analysis of CA IX expression in blood and tissue samples and to evaluate the significance of CA IX status for different renal cell carcinomas (RCCs). The expression of CA IX was determined in blood and tissue samples from 74 kidney cancer patients using reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), Western blotting (WB) and immunohistochemistry (IHC). The CA IX status was correlated with RCC type and tumor stage. IHC and WB provided evidence for a significantly higher expression of CA IX in clear cell RCC (CCRCC) specimens compared to other RCCs. RT-PCR assay revealed that 32.42% of all RCC patients possess CA9-positive cells in peripheral blood and three-quarters of CA9-positive patients were diagnosed with CCRCC. When the patients were subdivided according to tumor stage, decreased positivity was observed with higher tumor stage (50% in T1 vs. 17% in T3). Serum CA IX levels determined by ELISA were significantly higher in CCRCC patients than in non-CCRCC. A significant association between s-CA IX and CCRCC tumor stage was also determined (T1-87.51 vs. T3-341.98 pg/ml, p=0.046). We demonstrated that the CA IX expression profiles in blood and tissue samples from 74 kidney cancer patients are closely correlated with their histological subtypes. This is the first study reporting CA IX expression in blood and tissue samples from kidney cancer patients determined by four different methods.