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Abstract Micro-opto-electro-mechanical systems (MOEMS) biosensors are employed in various applications such as disease monitoring, drug investigation, detection of pollutants, and biological fluid studies. In this paper, a novel MOEMS biosensor based on a differential folded-flexure structure is introduced. The designed device is employed to detect prostate-specific antigen (PSA) protein and Hepatitis DNA. The target molecules cause a mechanical deflection in the folded-flexure; subsequently, the transmitted optical power across the finger, attached to the flexure, is modulated in proportion to the input concentration. Then, a photodiode power sensor measures the modulated optical power, where the output of the sensor is simply a current related to the target molecules’ concentrations. The employed readout circuit operates at a wavelength of λ = 1550 nm with a laser power of 1 µW. The dimensions of the proposed biosensor are considered to be 365 × 340 × 2 μm³, making this sensor small enough and suitable for integration. The designed biosensor provides notable features of mechanical deflection sensitivities of 0.2053 nm/(ng/ml) and 7.2486 nm/nM, optical transmittance sensitivities of 0.535504 × 10−3 1/(ng/ml) and 18.91 × 10−3 1/nM, total output sensitivities of 0.5398 (mA/W)/(ng/ml) and 19.059 (mA/W)/nM, and measurement ranges of 0-1000 ng/ml and 0-28.33 nM for PSA and Hepatitis DNA, respectively. The proposed system is a sensitive and powerful sensor that can play an important role in diagnosing many diseases.

Micro-opto-electro-mechanical systems (MOEMS) biosensors are employed in various applications such as disease monitoring, drug investigation, detection of pollutants, and biological fluid studies. In this paper, a novel MOEMS biosensor based on a differential folded-flexure structure is introduced. The designed device is employed to detect prostate-specific antigen (PSA) protein and Hepatitis DNA. The target molecules cause a mechanical deflection in the folded-flexure; subsequently, the transmitted optical power across the finger, attached to the flexure, is modulated in proportion to the input concentration. Then, a photodiode power sensor measures the modulated optical power, where the output of the sensor is simply a current related to the target molecules' concentrations. The employed readout circuit operates at a wavelength of λ = 1550 nm with a laser power of 1 µW. The dimensions of the proposed biosensor are considered to be 365 × 340 × 2 μm³, making this sensor small enough and suitable for integration. The designed biosensor provides notable features of mechanical deflection sensitivities of 0.2053 nm/(ng/ml) and 7.2486 nm/nM, optical transmittance sensitivities of 0.535504 × 10−3 1/(ng/ml) and 18.91 × 10−3 1/nM, total output sensitivities of 0.5398 (mA/W)/(ng/ml) and 19.059 (mA/W)/nM, and measurement ranges of 0-1000 ng/ml and 0-28.33 nM for PSA and Hepatitis DNA, respectively. The proposed system is a sensitive and powerful sensor that can play an important role in diagnosing many diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND: Prostate-specific antigen (PSA) levels are influenced by genetic variation unrelated to prostate cancer risk. Whether a genetic predisposition to a higher PSA level predisposes to a diagnostic work-up for prostate cancer is not known. METHODS: Participants were 3110 men of African and European ancestries ages 45-70, without prostate cancer and with a baseline PSA < 4 ng/mL, undergoing routine clinical PSA screening. The exposure was a polygenic score (PGS) comprising 111 single nucleotide polymorphisms associated with PSA level, but not prostate cancer. We tested whether the PGS was associated with a: 1) PSA value > 4 ng/mL, 2) International Classification of Diseases (ICD) code for an elevated PSA, 3) encounter with a urologist, or 4) prostate biopsy. Multivariable Cox proportional hazards models were adjusted for age and genetic principal components. Analyses were stratified by age (45-59 years, and 60-70 years old). Association estimates are per standard deviation change in the PGS. FINDINGS: The median age was 56.6 years, and 2118 (68%) participants were 45-59 years. The median (IQR) baseline PSA level was 1.0 (0.6-1.7) ng/mL. Among men ages 45-59, the PGS was associated with a PSA > 4 (hazard ratio [HR] = 1.35 [95% CI, 1.17-1.57], p = 4.5 × 10-5), an ICD code for elevated PSA (HR = 1.30 [1.12-1.52], p = 8.0 × 10-4), a urological evaluation (HR = 1.34 [1.14-1.57], p = 4.8 × 10-4), and undergoing a prostate biopsy (HR = 1.35 [1.11-1.64], p = 0.002). Among men ages 60-70, association effect sizes were smaller and not significant. INTERPRETATION: A predisposition toward higher PSA levels was associated with clinical evaluations of an elevated PSA among men ages 45-59 years. FUNDING: National Institutes of Health (NIH).

Abstract Background In this work, we compare input level, feature level and decision level data fusion techniques for automatic detection of clinically significant prostate lesions (csPCa). Methods Multiple deep learning CNN architectures were developed using the Unet as the baseline. The CNNs use both multiparametric MRI images (T2W, ADC, and High b-value) and quantitative clinical data (prostate specific antigen (PSA), PSA density (PSAD), prostate gland volume & gross tumor volume (GTV)), and only mp-MRI images (n = 118), as input. In addition, co-registered ground truth data from whole mount histopathology images (n = 22) were used as a test set for evaluation. Results The CNNs achieved for early/intermediate / late level fusion a precision of 0.41/0.51/0.61, recall value of 0.18/0.22/0.25, an average precision of 0.13 / 0.19 / 0.27, and F scores of 0.55/0.67/ 0.76. Dice Sorensen Coefficient (DSC) was used to evaluate the influence of combining mpMRI with parametric clinical data for the detection of csPCa. We compared the DSC between the predictions of CNN’s trained with mpMRI and parametric clinical and the CNN’s trained with only mpMRI images as input with the ground truth. We obtained a DSC of data 0.30/0.34/0.36 and 0.26/0.33/0.34 respectively. Additionally, we evaluated the influence of each mpMRI input channel for the task of csPCa detection and obtained a DSC of 0.14 / 0.25 / 0.28. Conclusion The results show that the decision level fusion network performs better for the task of prostate lesion detection. Combining mpMRI data with quantitative clinical data does not show significant differences between these networks (p = 0.26/0.62/0.85). The results show that CNNs trained with all mpMRI data outperform CNNs with less input channels which is consistent with current clinical protocols where the same input is used for PI-RADS lesion scoring. Trial registration The trial was registered retrospectively at the German Register for Clinical Studies (DRKS) under proposal number Nr. 476/14 & 476/19.

Background: In this work, we compare input level, feature level and decision level data fusion techniques for automatic detection of clinically significant prostate lesions (csPCa). Methods: Multiple deep learning CNN architectures were developed using the Unet as the baseline. The CNNs use both multiparametric MRI images (T2W, ADC, and High b-value) and quantitative clinical data (prostate specific antigen (PSA), PSA density (PSAD), prostate gland volume & gross tumor volume (GTV)), and only mp-MRI images (n = 118), as input. In addition, co-registered ground truth data from whole mount histopathology images (n = 22) were used as a test set for evaluation. Results: The CNNs achieved for early/intermediate / late level fusion a precision of 0.41/0.51/0.61, recall value of 0.18/0.22/0.25, an average precision of 0.13 / 0.19 / 0.27, and F scores of 0.55/0.67/ 0.76. Dice Sorensen Coefficient (DSC) was used to evaluate the influence of combining mpMRI with parametric clinical data for the detection of csPCa. We compared the DSC between the predictions of CNN's trained with mpMRI and parametric clinical and the CNN's trained with only mpMRI images as input with the ground truth. We obtained a DSC of data 0.30/0.34/0.36 and 0.26/0.33/0.34 respectively. Additionally, we evaluated the influence of each mpMRI input channel for the task of csPCa detection and obtained a DSC of 0.14 / 0.25 / 0.28. Conclusion: The results show that the decision level fusion network performs better for the task of prostate lesion detection. Combining mpMRI data with quantitative clinical data does not show significant differences between these networks (p = 0.26/0.62/0.85). The results show that CNNs trained with all mpMRI data outperform CNNs with less input channels which is consistent with current clinical protocols where the same input is used for PI-RADS lesion scoring. Trial registration: The trial was registered retrospectively at the German Register for Clinical Studies (DRKS) under proposal number Nr. 476/14 & 476/19. [ABSTRACT FROM AUTHOR]

Purpose: The objective was to assess the association between molecular imaging (mi) variables on [18F]DCFPyL-PET/CT with clinical and disease characteristics and prostate specific antigen (PSA) related variables in patients with biochemical recurrence of prostate cancer (BRPC). Material and methods: We analysed patients with BRPC after radical treatment. We obtained clinical and PSA variables: International Society of Urology Pathology (ISUP) grade group, European Association of Urology (EAU) risk classification, PSA (PSA≤1ng/ml, 12), PSA doubling time (PSAdt) and PSA velocity (PSAvel). All PET/CT scans were reviewed with the assistance of automated Prostate Molecular Imaging Standardized Evaluation (aPROMISE) software and lesions' segmentation in positive scans was performed using this platform. Standardized uptake value (SUV) derived variables; tumour burden variables [whole-body tumour volume (wbTV), whole-body tumour lesion activity (wbTLA) and whole-body mi PSMA (wbPSMA)] and miTNM staging were obtained. Cut-off of PSA and kinetics able to predict PET/CT results were obtained. Associations between disease and mi variables were analysed using ANOVA, Kruskal-Wallis and Spearman's correlation tests. Multivariate analysis was also performed. Results: Two hundred and seventy-five patients were studied. [18F]DCFPyL-PET/CT were positive in 165/275 patients. In multivariate analysis, moment of biochemical recurrence, ISUP group, PSA level and PSAvel showed significant association with the detection rate. miTNM showed significant association with PSA level (p<0.001) and kinetics (p<0.001), being higher in patients with metastatic disease. Both PSA and PSAvel showed moderate correlation with wbTV, wbTLA and wbPSMA (p<0.001). A weak correlation with SUVs was found. Mean wbTV, wbTLA and wbPSMA values were significantly higher in PSA > 2ng/ml, PSAdt ≤ 6 months and PSAvel ≥ 0.2ng/ml/month groups. Also, wbTV (p=0.039) and wbPSMA (p=0.020) were significantly higher in patients with ISUP grade group 5. PSA and PSAvel cut-offs (1.15 ng/ml and 0.065 ng/ml/month) were significantly associated with a positive PET/CT. Conclusion: Higher PSA values, unfavourable PSA kinetics and ISUP grade group 5 were robust predictive variables of larger tumour burden variables on [18F]DCFPyL PET/CT assessed by aPROMISE platform. [ABSTRACT FROM AUTHOR]

Copyright of Micronanoelectronic Technology is the property of Micronanoelectronic Technology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To determine the relationship between the prostate volume and the serum values of prostate specific antigen among patients in the "grey zone", classified according to their age group. Gray zone represents serum prostate specific antigen values between 4.1 ng/ml to 10 ng/ml. Material and Methods: Prospective and retrospective 1420 patients classified in four age-groups with LUTS (Lower Urinary Tract Symptoms) were analyzed. Patients were treated for Benign Prostate Hyperplasia (BPH) in the urology clinical at the University Clinical Center of Kosovo during the period of January 2010-October 2020. Data were recorded from patients according to age, prostate size estimated by trans abdominal ultrasound using 3.5 MHz ultrasonography, according to the ellipsoid formula, V = D1 × D2 × D3/2.5, Volume of prostate (V)=T × AP × CC × Pi/6 where T=Transverse diameter, AP=Antero Posterior diameter, CC=Cranial Caudal diameter. Patients with confirmed prostate cancer were excluded from the study. Statistical analyses used t-test and ANOVA (Analysis of Variance) with 95% and 99% confidence intervals. Results: For the grey zone patients, these mean values were 44.6 cm3 and 5.9 ng/mL. Conclusions: The data provide evidence to support that prostate volume and serum Prostate Specific Antigen (PSA) concentration significantly correlate with aging and within the grey zone patients. [ABSTRACT FROM AUTHOR]

Objectives: The study aimed to evaluate late toxicity after whole pelvic irradiation in prostate cancer patients. Methods: A cross-sectional study of 15 non-metastatic prostatic cancer patients treated with radiotherapy were included. The analysis was conducted at Baghdad Radiotherapy and Nuclear Medicine Center, Baghdad Medical City Complex, Baghdad, Iraq, between December 2022 and May 2022. Data were collected retrospectively with the review of medical records. The following variables were studied: age, residency (address), smoking habits, TNM staging, histopathology, grades, GS, initial PSA concentration, ADT, treatment modality, the dose of RT, risk group, adverse effects including diarrhoea, pain, dysuria, anaemia, retention, haematuria, lymphedema, incontinence, urgency and sexual dysfunction, PTV95%, and OAR constraints doses. Results: The mean age of patients was 68.47 ± 8.15 years, with a median age of 65 and most patients above 60 years. Most of the patients were smokers, 14 (93.3%). Most patients have a history of comorbid condition 14 (93.3%). All prostatic cancer cases in this study were adenocarcinoma. Stage I recorded in 3 (20%) patients, stage III in 6 (40%), and stage IV in 6 (40%). Regarding the Gleason score, the median GS in this study was 7. The mean of PSA was 39.09 ± 38.74 ng/mL (median=23 ng/mL). Yet, no retention, anaemia, hematuria, or lymphedema was recorded. Approximately the percentage of adverse effects was 26.7% diarrhoea, 26.7% pain, 6.7% BPR, 20% dysuria, 6.7% incontinence, 13.4% urgency, and 60% sexual dysfunction. Conclusions: To the best of our knowledge, this is the first study in Iraq to evaluate late toxicity after whole pelvic irradiation in prostate cancer patients. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men, with a rising global incidence. Currently, the PCa landscape is vastly different between developed countries and Africa. Of note, owing to various biological, socioeconomic and institutional factors, black African men often present with more advanced disease and suffer greater mortality. This review will focus on the burden of PCa globally and in Africa, compare the state of the disease in Africa with that in more developed regions of the world, and answer the question why it can sometimes look like a ‘different’ disease compared with developed regions. In addition, we address the racial disparities of PCa.

Urology provides critical medical treatment that has the potential to save lives and greatly improve quality of life. Although there is a growing need for urological care, South Africa (SA) now faces an unmet need for these services, and junior doctors have limited exposure to urology. SA has a total of 347 urologists who are actively practising and registered with the Health Professions Council of South Africa. This means that there is a ratio of only 0.56 urologists per 100 000 people in the population. The ratio is even more dire if we only include urologists in the public sector. This article offers pragmatic strategies for addressing common urological conditions. These guidelines adhere to international standards and can be adopted at all levels of healthcare, with the exception of a few advanced imaging needs.

As a representative transition metal dichalcogenide, molybdenum disulfide (MoS2) has unique electronic, optical, and mechanical properties that exhibit advantages in the construction of biosensing interfaces. In this study, we explored the construction of a MoS2-based aptamer sensor and investigated its application for high-precision detection of prostate specific antigen (PSA) in serum. Carboxyl group-modified MoS2 was stably bonded to the surface of an aminated electrode as a substrate structure, and the electrode was further modified with biocompatible membrane polydopamine and PSA aptamers to form an aminated screen-printed electrode/carboxylated MoS2/polydopamine (SPE-NH2/MoS2-COOH/PDA)-based aptamer sensor, which achieved ultrasensitive detection of PSA at 0.001 pg/mL ∼ 1 ng/mL with a limit of detection (LOD) of 0.16 fg/mL. The detection results of related interfering substances, such as L-cysteine, alpha fetoprotein (AFP), carcinoembryonic antigen (CEA) and bovine serum albumin (BSA), proved that the sensor had good selectivity. Then, repeated test results of multiple sensors verified that the aptamer sensors had good reproducibility between sensors. Finally, the practical application of the aptamer sensor was evaluated by a blank spiking method, which demonstrated its great clinical application potential. In summary, our study has provided ideas for the application of MoS2 composite-based aptamer sensing interfaces for potential precision medicine needs.

Summary: Background: Prostate-specific antigen (PSA) levels are influenced by genetic variation unrelated to prostate cancer risk. Whether a genetic predisposition to a higher PSA level predisposes to a diagnostic work-up for prostate cancer is not known. Methods: Participants were 3110 men of African and European ancestries ages 45–70, without prostate cancer and with a baseline PSA < 4 ng/mL, undergoing routine clinical PSA screening. The exposure was a polygenic score (PGS) comprising 111 single nucleotide polymorphisms associated with PSA level, but not prostate cancer. We tested whether the PGS was associated with a: 1) PSA value > 4 ng/mL, 2) International Classification of Diseases (ICD) code for an elevated PSA, 3) encounter with a urologist, or 4) prostate biopsy. Multivariable Cox proportional hazards models were adjusted for age and genetic principal components. Analyses were stratified by age (45–59 years, and 60–70 years old). Association estimates are per standard deviation change in the PGS. Findings: The median age was 56.6 years, and 2118 (68%) participants were 45–59 years. The median (IQR) baseline PSA level was 1.0 (0.6–1.7) ng/mL. Among men ages 45–59, the PGS was associated with a PSA > 4 (hazard ratio [HR] = 1.35 [95% CI, 1.17–1.57], p = 4.5 × 10−5), an ICD code for elevated PSA (HR = 1.30 [1.12–1.52], p = 8.0 × 10−4), a urological evaluation (HR = 1.34 [1.14–1.57], p = 4.8 × 10−4), and undergoing a prostate biopsy (HR = 1.35 [1.11–1.64], p = 0.002). Among men ages 60–70, association effect sizes were smaller and not significant. Interpretation: A predisposition toward higher PSA levels was associated with clinical evaluations of an elevated PSA among men ages 45–59 years. Funding: National Institutes of Health (NIH).

Global increase in cancer incidence has prompted the search for natural bioactive products which are readily available, safer and more affordable. Beta-D-glucan polysaccharide (ßDgP) is a phytochemical fractionate of an edible mushroom Auricularia polytricha known to have anticancer property but information about the actual mechanism underlying its therapeutic property is lacking. This research investigates the tumor regulatory effect of Beta-D-glucan polysaccharide on some tumor markers; p53 and Prostate Specific Antigen (PSA) in nitrosobis amine (NA) - induced prostate tumor model of Wister rat. Twenty-four male Wister rats were divided into four groups with six rats in each group. Group A served as normal control while treatment groups: B (5mg/kgbw nitrosobis amine only); C and D (placed on 120 mg/kgbw and 250 mg/kgbw respectively) after inducing tumor. The experiment lasted for 10 weeks. At termination, ELISA method was used to evaluate PSA levels; p53 tumor marker was assessed using immunohistochemical methods; histological alterations were examined using routine H&E technique. Results shown that p53 and PSA levels increased significantly (at p=0.05) in group B (tumor control) when compared to normal control. Increase in papillary fronds, basal cell hyperplasia and prostatic concretions depicted cytoarchitectural alterations in tumor control group. However, expression of p53 and PSA was down-regulated significantly (p=0.05) when compared to tumor control, and histological distortions reversed in a dose-dependent manner, following administration of graded concentration of ßDgP. Findings from the present study have revealed the anti-tumor property of ßDgP in NA-induced prostate tumor model in Wister rat. [ABSTRACT FROM AUTHOR]

Objectives: To compare the safety and efficacy of holmium laser enucleation of the prostate (HoLEP) and bipolar palsmakinetic enucleation of the prostate (BPEP) for patients with benign prostatic hyperplasia (BPH) and prostate volumes 50-120 mL. Methods: a total of 52 patients were prospectively randomized and enrolled in this study at Zagazig university hospitals. All patients were preoperatively evaluated using prostate volume measurement, the International Prostate Symptom Scores (IPSS) questionnaire, a quality-of-life (QoL) questionnaire and international index for erectile function-5 (IIEF-5). Measurement of maximum urinary flow rate (Qmax), post-void residual urine volume (PVR) and blood sample analysis for determination of prostate-specific antigen (PSA) and haemoglobin concentration. Patients were evaluated peri-operatively and postoperatively at 1, 3, 6 and 12 months with documentation of any complication. Results: Of 52 patients enrolled in this study, 47 patients completed 12 months of follow-up. There were statistically insignificant differences between both groups regarding the preoperative and intraoperative data. Perioperatively, bleeding, need for blood transfusion and hemoglobin drop were higher in the HoLEP group. There were no statistically significant differences in the post-operative follow-up data between both groups. Conclusion: In terms of surgical safety and efficacy BPEP is comparable to HoLEP for moderately to markedly enlarged prostates, with indication for surgical intervention. [ABSTRACT FROM AUTHOR]

Specific and label‐free detection of biological interactions is paramount to a plethora of technological applications ranging from home‐care diagnostics to smart agriculture and home security. The biologically‐modified field‐effect transistor (BioFET) is a promising sensing platform due to its inherent signal amplification, low power, and miniaturization. In the following a low‐cost meta‐nano‐channel BioFET (MNC BioFET) is reported that provides means to electrostatically control the size, shape, and location of the conducting channel such as to enhance the coupling between the locally‐occurring electrostatics of the biological interactions and the electrodynamics of the underlying conducting channel. Moreover, it provides means to electrostatically control the Debye screening length at the sensing area to increase the readout signal. The MNC BioFET is fabricated in a large‐scale silicon chip foundry that ensures robustness and stability, optimal noise levels and signal amplification, repeatability, and ultimate miniaturization with the potential for high‐end multiplexing in ultra‐small samples. In the current study, a specific and label‐free sensing of prostate specific antigen with the MNC BioFET is demonstrated, and show the dependency of the sensor signal on the channel configuration. Finally, an order of magnitude enhancement in readout signal is demonstrated by the electrostatic control of the screening length at the sensing area. [ABSTRACT FROM AUTHOR]

Prostate cancer is one of the most common malignancies in men. Early detection of prostate cancer is largely determined by the widely used prostate specific antigen (PSA) blood test. However, as a diagnostic and prognostic test of prostate cancer, PSA has limited specificity, sensitivity and leads to hyper or underdiagnosis, which, in turn, can lead to excessive treatment. There fore, it is very important to develop diagnostic markers that can be used to determine prostate cancer at an early stage of development, assess the possible progression of the disease and prescribe optimal therapy. Significant progress has been made in the discovery of biomarkers for prostate cancer. For example, biomarkers such as %-free PSA, Prostate Health Index (PHI) or 4K score can be used to increase specificity and reduce the number of unnecessary biopsies, while the PCA3 test can be used to reduce the number of repeated biopsies in men with previously negative biopsy. To determine aggressiveness and predict the outcome of the disease, tissue multigenic tests can be used, such as: T2-ERG, ExoDx, SelectMDx and ConfirmMDx, Prolaris, Oncoytype DX, Decipher. The development of such diagnostic tests opens up new opportunities for improving the diagnosis of prostate cancer, prognosis and decision-making on the appointment of therapy. And with the increase in their availability, finally, the possibility of an individual approach to the appointment of treatment for men with prostate cancer appears on the horizon. This review paper presents the data on the most advanced diagnostic biomarkers of prostate cancer.

Copyright of Scire Salutis is the property of CBPC - Companhia Brasileira de Producao Cientifica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A novel "double chemical bonding" electrochemical peptide biosensor 2FcP-GA-GDY(Fe)@NMIL-B was developed for highly selective, ultrasensitive, and ultrastable identification of prostate-specific antigen (PSA). The C–Fe–O chemical bond linking Fe-Graphdiyne (Fe-GDY) with NH 2 -MIL88B(Fe) (NMIL88B) as the first chemical bonding of electrode carrier Fe-GDY@NH 2 -MIL88B(Fe) (GDY(Fe)@NMIL) significantly accelerates electron transport. With glutaraldehyde (GA) as a crosslinking agent, the Schiff-base –N C- formed by GDY(Fe)@NMIL nanocomposites links the two Fc molecules labeled peptides (2FcP) as the second chemical bonding, facilitating high-density attachment of peptides to the electrode carrier in a firm manner. When the PSA analyte is introduced to identify and cleave the specific peptide, the release of ferrocene from its head leads to a decrease in the electrical signal, enabling sensitive detection. The prepared sensing platform exhibits exceptional analytical performance for PSA with an extended linear response range from 10 fg mL−1 to 50 ng mL−1. Additionally, the detection limit has been significantly reduced to an ultra-low level of only 0.94 fg mL−1, surpassing those reported in most literature by several orders of magnitude. Moreover, the 2FcP-GA-GDY(Fe)@NMIL-B sensor has excellent selectivity and stability while also showcasing great potential for practical application of PSA detection in human serum using the standard addition method. [Display omitted] • Electrochemical peptide sensor with dual chemical bonding for PSA detection. • The first chemical bonding C–Fe–O accelerate electron transport of sensor. • The second chemical bonding –N C- enhance detection stability and sensitivity. • Detection limits about 3 orders of magnitude lower than other biosensors. • The sensor shows a wide linear range of 10 fg mL−1 to 50.0 ng mL−1 [ABSTRACT FROM AUTHOR]

A spatial- and potential-resolved ratiometric electrochemiluminescent (ECL) immunosensor was developed for prostate specific antigen detection in a label-free mode. CdS quantum dots (CdS QDs) and luminol-gold nanoparticles (luminol-Au NPs) were the potential-resolved electrochemiluminescence emitters and H2O2 was used as a co-reactant. The cathodic signal from the CdS QD electrode served as the working signal and the anodic signal from luminol-Au NPs as the reference. For prostate specific antigen detection, several concentrations of prostate specific antigen were immobilized on the CdS QDs modified electrode and a fixed concentration of the prostate specific antigen was modified on the luminol-Au NPs modified electrode. The prostate specific antigen levels were quantified by the electrochemiluminescence signal ratio of the cathodic and anodic (ECLcathodic/ECLanodic). Under the optimized conditions, the ratio of the cathodic and anodic signals (ECLcathodic/ECLanodic) had a linear relationship with the logarithm of (C, g mL−1) of prostate specific antigen concentration from 1.0 × 10−11 to 1.0 × 10−7 g mL−1. The detection limit was 5.0 × 10−12 g mL−1. Prostate specific antigen was determined in human serum and the recoveries were from 80.0% to 107.0%. The label-free electrochemiluminescence immunosensor offers simplicity and reliability for human serum with potential for clinical application. [ABSTRACT FROM AUTHOR]

Objective*To investigate the expression and diagnostic value of prostate specific antigen (PSA), tumor abnormal protein (TAP) and colon cancer metastasis related gene 1 (MACC1) in the blood of patients with prostate cancer. Methods·One hundred and seven patients with prostate cancer (case group) admitted to Dahua Hospital, Xuhui District, Shanghai, from January 2019 to December 2020 were retrospectively analyzed, and 60 healthy people (control group) who underwent physical examination in the hospital in the same period were selected. The levels of blood PSA, TAP and MACC1 in the two groups, as well as their correlation with Gleason score and T stage, were analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the value of various indexes in the diagnosis of prostate cancer. Results*The levels of blood PSA, TAP and MACC1 in the case group were significantly higher than those in the control group (P<0.05). With the increase of Gleason grade, the levels of blood PSA, TAP and MACC1 increased gradually. With the progress of T stage, the levels of blood PSA, TAP and MACC1 increased gradually. The levels of PSA and MACC1 in the patients with lymph node metastasis were significantly higher than those without lymph node metastasis, but the levels of TAP in the patients with lymph node metastasis were significantly lower than those without lymph node metastasis (P<0.05). The analysis results of ROC curve showed that the AUC of PSA in the diagnosis of prostate cancer was 0.764, the sensitivity was 86.12%, the specificity was 88.63%, and the cut-off value was 6.01 μg/L. The AUC of TAP in the diagnosis of prostate cancer was 0.796, the sensitivity was 88.18%, the specificity was 89.58%, and the cut-off value was 135.62 μm2. The AUC of MACC1 in the diagnosis of prostate cancer was 0.873, the sensitivity was 78.46%, the specificity was 80.10%, and the cut-off value was 37.80 pg/mL. The AUC (0.941), sensitivity (93.15%) and specificity (94.08%) of combined detection were higher than those of any single detection (P<0.05). Spearman correlation analysis showed that the blood PSA, TAP and MACC1 levels were positively correlated with Gleason score (r=0.648, 0.513, 0.501; P=0.000), and with T stage (r=0.616, 0.537, 0.542; P=0.000). Conclusion*Blood PSA, TAP and MACC1 are closely related to Gleason score and T stage of prostate cancer, which has some value in the diagnosis of prostate cancer, and the combined detection of three items has higher diagnostic value. [ABSTRACT FROM AUTHOR]

Prostate cancer is one of the most frequent cancers in men. Although several treatment options exist, their clinical effectiveness is still not satisfactory. One the possible reason of such situation might be the presence of myeloid-derived suppressor cells (MDSC) and their pro-tumorigenic activity. MDSC possess immunosuppressive ability and in many studies were shown to support tumor development and progression. In this study we addressed the question whether commonly used therapies of prostate cancer affect the level of MDSC populations in the patients’ blood. We compared the level of granulocytic (Gr-MDSC), monocytic (Mo-MDSC) and early stage MDSC (eMDSC) in the blood of patients at different clinical stage and different tumor grading scores, who underwent either surgery or hormonal therapy alone or were given a combined treatment, including e.g. radiotherapy. The obtained results showed that the level of Gr-MDSC was significantly lower in all treated patients comparing to untreated group. On the other hand, surgery or hormonal therapy alone did not affect the level of Mo-MDSC. These results were independent of the PSA level, the tumor grading and clinical stage of the patients. In conclusion, we suggest that Mo-MDSC should be considered as a potential therapy target in the course of prostate cancer treatment to enhance its anti-tumor effectiveness.

Background: Prostate specific antigen (PSA) is an important biomarker to monitor patients after treated with radiation therapy (RT). The aim of this study is to evaluate the relationship between the PSA data and prostate cancer recurrence using the joint modeling. Methods: This historical cohort study was performed on 422 prostate cancer patients. Inclusion criteria included: patients with localized prostate cancer referring to Cancer Institute in Tehran (Iran) from 2007 to 2012, and under radiation therapy. Joint model has two components or sub-models. We showed the results by parameter estimating the longitudinal sub-model and survival sub-model. EM algorithm, Newton-Gauss and Gauss-Hermit law were used for final model parameters. R software version 3.2 was used for statistical analysis. Results: In this study, considering the inclusion and exclusion criteria, out of 422 patients, the data on 314 cases were selected for analysis and the main result of joint model was obtained. PSA directly and significantly was associated with recurrence risk, therefore increasing 2.6 ml/lit PSA (one unit in transformed PSA) increases 39% recurrence risk (95% CI for RR: 1.09-1.77). Also, slope of PSA trend has significant association with prostate cancer recurrence risk (95% CI for RR: 1.05-1.41). Conclusion: This study showed a significant relationship between PSA, and its slope with the recurrence risk by joint model, with regard to the pathological, demographic and clinical features in the Iranian population.

Purpose: Accumulating evidence has attracted attention to the androgen receptor (AR) as a biomarker and therapeutic target in breast cancer. We hypothesized that AR activity within the tumor has clinical implications and investigated whether androgen responsive serum factors might serve as a minimally invasive indicator of tumor AR activity.Methods: Based on a comprehensive gene expression analysis of an AR-positive, triple negative breast cancer patient-derived xenograft (PDX) model, 163 dihydrotestosterone (DHT)-responsive genes were defined as an androgen responsive gene set. Among them, we focused on genes that were DHT-responsive that encode secreted proteins, namely KLK3, AZGP1 and PIP, that encode the secreted factors prostate specific antigen (PSA), zinc-alpha-2-glycoprotein (ZAG) and prolactin induced protein (PIP), respectively. Using AR-positive breast cancer cell lines representing all breast cancer subtypes, expression of candidate factors was assessed in response to agonist DHT and antagonist enzalutamide. Gene set enrichment analysis (GSEA) was performed on publically available gene expression datasets from breast cancer patients to analyze the relationship between genes encoding the secreted factors and other androgen responsive gene sets in each breast cancer subtype.Results: Anti-androgen treatment decreased proliferation in all cell lines tested representing various tumor subtypes. Expression of the secreted factors was regulated by AR activation in the majority of breast cancer cell lines. In GSEA, the candidate genes were positively correlated with an androgen responsive gene set across breast cancer subtypes.Conclusion: KLK3, AZGP1 and PIP are AR regulated and reflect tumor AR activity. Further investigations are needed to examine the potential efficacy of these factors as serum biomarkers. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) gold-standard diagnosis relies on prostate biopsy, which is currently overly recommended since other available noninvasive tools such as prostate-specific antigen (PSA) multiparametric MRI (mMRI) showed low diagnostic accuracy or high costs, respectively. The aim of the study was to determine the accuracy of a novel Bioelectric Impedance Analysis (BIA) test endorectal probe for the selection of patients candidate to prostate biopsy and in particular the clinical value of three different parameters such as resistance (R), reactance (Xc), and phase angle (PA) degree. One-hundred twenty-three consecutive candidates to prostate biopsy and 40 healthy volunteers were enrolled. PSA and PSA density (PSAD) determinations, Digital Rectal Examination (DRE), and the novel BIA test were analyzed in patients and controls. A 16-core prostate biopsy was performed after a mMRI test. The study endpoints were to determine accuracy of BIA test in comparison with PSA, PSAD levels, and mMRI and obtain prostate cancer (PCa) prediction by BIA test. The Mann-Whitney U-test, the Wilkoxon rank test, and the Holm-Bonferroni’s method were adopted for statistical analyses, and a computational approach was also applied to differentiate patients with PCa from those with benign disease. Combined PSA, PSAD, DRE, and trans-rectal ultrasound test failed to discern patients with PCa from those with benign disease (62.86% accuracy). mMRI PIRADS ≥3 showed a sensitivity of 83% and a specificity of 59%. The accuracy in discerning PCa increased up to 75% by BIA test (sensitivity 63.33% and specificity 83.75%). The novel finger probe BIA test is a cheap and reliable test that may help to improve clinical multifeature noninvasive diagnosis for PCa and reduce unnecessary biopsies.

Prostate cancer (PCa) gold-standard diagnosis relies on prostate biopsy, which is currently overly recommended since other available noninvasive tools such as prostate-specific antigen (PSA) multiparametric MRI (mMRI) showed low diagnostic accuracy or high costs, respectively. The aim of the study was to determine the accuracy of a novel Bioelectric Impedance Analysis (BIA) test endorectal probe for the selection of patients candidate to prostate biopsy and in particular the clinical value of three different parameters such as resistance (R), reactance (Xc), and phase angle (PA) degree. One-hundred twenty-three consecutive candidates to prostate biopsy and 40 healthy volunteers were enrolled. PSA and PSA density (PSAD) determinations, Digital Rectal Examination (DRE), and the novel BIA test were analyzed in patients and controls. A 16-core prostate biopsy was performed after a mMRI test. The study endpoints were to determine accuracy of BIA test in comparison with PSA, PSAD levels, and mMRI and obtain prostate cancer (PCa) prediction by BIA test. The Mann-Whitney U -test, the Wilkoxon rank test, and the Holm-Bonferroni's method were adopted for statistical analyses, and a computational approach was also applied to differentiate patients with PCa from those with benign disease. Combined PSA, PSAD, DRE, and trans-rectal ultrasound test failed to discern patients with PCa from those with benign disease (62.86% accuracy). mMRI PIRADS ≥3 showed a sensitivity of 83% and a specificity of 59%. The accuracy in discerning PCa increased up to 75% by BIA test (sensitivity 63.33% and specificity 83.75%). The novel finger probe BIA test is a cheap and reliable test that may help to improve clinical multifeature noninvasive diagnosis for PCa and reduce unnecessary biopsies. [ABSTRACT FROM AUTHOR]

We demonstrate that prostate cancer can be identified by flow cytometric profiling of blood immune cell subsets. Herein, we profiled natural killer (NK) cell subsets in the blood of 72 asymptomatic men with Prostate-Specific Antigen (PSA) levels < 20 ng ml-1, of whom 31 had benign disease (no cancer) and 41 had prostate cancer. Statistical and computational methods identified a panel of eight phenotypic features ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]) that, when incorporated into an Ensemble machine learning prediction model, distinguished between the presence of benign prostate disease and prostate cancer. The machine learning model was then adapted to predict the D’Amico Risk Classification using data from 54 patients with prostate cancer and was shown to accurately differentiate between the presence of low-/intermediate-risk disease and high-risk disease without the need for additional clinical data. This simple blood test has the potential to transform prostate cancer diagnostics.

The current screening-test for prostate cancer, affecting 10% of men worldwide, has a high false negative rate and a low true positive rate. A more reliable screening test is needed. Circulating-Tumor-Cells (CTC) provide a biomarker for early carcinogenesis, cancer progression and treatment effectiveness. The cytology-based ISET®-CTC Test is a clinically validated blood test with high sensitivity and specificity. This study aimed to evaluate the ISET®-CTC test combined with prostate-specific-marker staining as a screening test for the detection of prostate cancer. We selected a group of 47 men from our ongoing CTC screening study involving 2,000 patient-tests from Sep-2014 to July-2019, who also underwent standard diagnostic cancer testing before or after CTC testing. While 20 of the 47 men were diagnosed with prostate cancer before the ISET®-CTC test, 27 men underwent screening. We studied the CTC identified in 45 CTC-positive men by Immuno-Cyto-Chemistry (ICC) assays with the prostate-specific-marker PSA. CTC were ICC-PSA-marker positive in all men diagnosed with primary prostate cancer (n = 20). Secondary cancers were detected in 63% (n = 7/11) of men with mixed CTC-population (ICC-PSA-positive/ICC-PSA-negative). Of the 27 men screened, 25 had CTC, and 84% of those (n = 20) were positive for the prostate-specific-PSA-marker. Follow-up testing suggested suspected prostate cancer in 20/20 men by a positive PSMA-PET scan, and biopsies performed in 45% (n = 9/20) men confirmed the diagnosis of early prostate cancer. Kidney cancer or B-cell lymphoma were detected in two men with ICC-PSA-marker negative CTC. Our study suggests that the combination of ISET®-CTC and ICC-PSA-marker-testing has an estimated positive-predictive-value (PPV) of 99% and a negative-predictive-value (NPV) of 97%, providing a more reliable screening test for prostate cancer than the standard PSA-blood-test (PPV = 25%; NPV = 15.5%). Our findings warrant further studies to evaluate the new test's potential for prostate cancer screening on a population level.

Objective: We examined risk factors associated with prostate specific antigen (PSA) and hematocrit (hct) elevation during testosterone replacement therapy (TRT) in patients with testosterone deficiency (TD). Methods: We retrospectively analyzed the medical records of patients receiving TRT for ≥3 months. We investigated the following parameters: age, body mass index, comorbidities, TRT type, TRT duration, pre-TRT prostate volume, pre- and post-TRT serological tests, prostate biopsies, prostate cancer diagnoses, pre- and post-TRT aging male symptom scale scores, hct elevation, and PSA elevation. The patients were divided into two groups based on the PSA elevation status for comparison, following which we analyzed the predictive factors for PSA elevation. They were also divided into two groups based on hct elevation status. Results: The PSA elevation group showed a statistically significantly higher mean age, pre-TRT prostate volume, and PSA level compared to the non-elevation group. The PSA non-elevation group showed a significantly higher percentage of smokers, while the PSA elevation group showed a statistically significantly higher prevalence of benign prostatic hyperplasia (BPH_LUTS). The results demonstrated that a large pre-TRT prostate volume, high pre-TRT PSA levels, BPH_LUTS, and being a non-smoker were the contributing factors for PSA elevation. The hct elevation group showed statistically significantly higher pre-TRT Hb, hct, and post-TRT testosterone levels, and dyslipidemia rates, as well as a non-statistically significant prevalence of testosterone enanthate (TE) and testosterone undecanoate (TU) intramuscular injection. The pre-TRT Hb and hct levels were contributing factors for hct elevation during TRT. TE injection showed marginal statistical significance. Conclusions: We identified large prostate volumes, high PSA levels, BPH_LUTS, and being non-smokers prior to TRT as risk factors for PSA elevation during TRT. Interestingly, we found that TRT-induced hct elevation was likely to occur in patients with high pre-TRT Hb and hct levels. Additionally, the hct levels should be monitored when using TE for TRT.

Background: Prostate specific antigen (PSA) is an important biomarker to monitor patients after treated with radiation therapy (RT). The aim of this study is to evaluate the relationship between the PSA data and prostate cancer recurrence using the joint modeling. Methods: This historical cohort study was performed on 422 prostate cancer patients. Inclusion criteria included: patients with localized prostate cancer referring to Cancer Institute in Tehran (Iran) from 2007 to 2012, and under radiation therapy. Joint model has two components or sub-models. We showed the results by parameter estimating the longitudinal sub-model and survival sub-model. EM algorithm, Newton-Gauss and Gauss-Hermit law were used for final model parameters. R software version 3.2 was used for statistical analysis. Results: In this study, considering the inclusion and exclusion criteria, out of 422 patients, the data on 314 cases were selected for analysis and the main result of joint model was obtained. PSA directly and significantly was associated with recurrence risk, therefore increasing 2.6 ml/lit PSA (one unit in transformed PSA) increases 39% recurrence risk (95% CI for RR: 1.09-1.77). Also, slope of PSA trend has significant association with prostate cancer recurrence risk (95% CI for RR: 1.05-1.41). Conclusion: This study showed a significant relationship between PSA, and its slope with the recurrence risk by joint model, with regard to the pathological, demographic and clinical features in the Iranian population. [ABSTRACT FROM AUTHOR]

The current screening-test for prostate cancer, affecting 10% of men worldwide, has a high false negative rate and a low true positive rate. A more reliable screening test is needed. Circulating-Tumor-Cells (CTC) provide a biomarker for early carcinogenesis, cancer progression and treatment effectiveness. The cytology-based ISET®-CTC Test is a clinically validated blood test with high sensitivity and specificity. This study aimed to evaluate the ISET®-CTC test combined with prostate-specific-marker staining as a screening test for the detection of prostate cancer. We selected a group of 47 men from our ongoing CTC screening study involving 2,000 patient-tests from Sep-2014 to July-2019, who also underwent standard diagnostic cancer testing before or after CTC testing. While 20 of the 47 men were diagnosed with prostate cancer before the ISET®-CTC test, 27 men underwent screening. We studied the CTC identified in 45 CTC-positive men by Immuno-Cyto-Chemistry (ICC) assays with the prostate-specific-marker PSA. CTC were ICC-PSA-marker positive in all men diagnosed with primary prostate cancer (n = 20). Secondary cancers were detected in 63% (n = 7/11) of men with mixed CTC-population (ICC-PSA-positive/ICC-PSA-negative). Of the 27 men screened, 25 had CTC, and 84% of those (n = 20) were positive for the prostate-specific-PSA-marker. Follow-up testing suggested suspected prostate cancer in 20/20 men by a positive PSMA-PET scan, and biopsies performed in 45% (n = 9/20) men confirmed the diagnosis of early prostate cancer. Kidney cancer or B-cell lymphoma were detected in two men with ICC-PSA-marker negative CTC. Our study suggests that the combination of ISET®-CTC and ICC-PSA-marker-testing has an estimated positive-predictive-value (PPV) of 99% and a negative-predictive-value (NPV) of 97%, providing a more reliable screening test for prostate cancer than the standard PSA-blood-test (PPV = 25%; NPV = 15.5%). Our findings warrant further studies to evaluate the new test's potential for prostate cancer screening on a population level. [ABSTRACT FROM AUTHOR]

To identify the associated factors determining prostate cancer detection using transrectal ultrasound (TRUS)-guided prostate biopsy, within a multi-ethnic Malaysian population with prostate specific antigen (PSA) between 4.0 and 10.0 ng/ml. Study subjects included men with initial PSA between 4.0 and 10.0 ng/ml that have undergone 12-core TRUS-guided prostate biopsy between 2009 and 2016. The prostate cancer detection rate was calculated, while potential factors associated with detection were investigated via univariable and multivariable analysis. A total of 617 men from a multi-ethnic background encompassing Chinese (63.5%), Malay (23.1%) and Indian (13.3%) were studied. The overall cancer detection rate was 14.3% (88/617), which included cancers detected at biopsy 1 (first biopsy), biopsy 2 (second biopsy with previous negative biopsy) and biopsy ≥ 3 (third or more biopsies with prior negative biopsies). Indian men displayed higher detection rate (23.2%) and increased risk of prostate cancer development (OR 1.85, 95% CI 1.03–3.32, p < 0.05), compared to their Malay (9.8%) and Chinese (14.0%) counterparts. Multivariable analysis revealed that ethnicity and PSA density (PSAD) are independent factors associated with overall prostate cancer detection rate. A unit increase of PSAD reflected an increase in PSA after controlling for prostate volume. Prostate cancer detection in Malaysia is comparatively lower. Our study suggests that ethnicity and PSA density should be considered when recommending first or repeat TRUS-guided prostate biopsy for prostate cancer detection in a multi-ethnic Malaysian population. [ABSTRACT FROM AUTHOR]

Prostate cancer is one of the most frequent cancers in men. Although several treatment options exist, their clinical effectiveness is still not satisfactory. One the possible reason of such situation might be the presence of myeloid-derived suppressor cells (MDSC) and their pro-tumorigenic activity. MDSC possess immunosuppressive ability and in many studies were shown to support tumor development and progression. In this study we addressed the question whether commonly used therapies of prostate cancer affect the level of MDSC populations in the patients’ blood. We compared the level of granulocytic (Gr-MDSC), monocytic (Mo-MDSC) and early stage MDSC (eMDSC) in the blood of patients at different clinical stage and different tumor grading scores, who underwent either surgery or hormonal therapy alone or were given a combined treatment, including e.g. radiotherapy. The obtained results showed that the level of Gr-MDSC was significantly lower in all treated patients comparing to untreated group. On the other hand, surgery or hormonal therapy alone did not affect the level of Mo-MDSC. These results were independent of the PSA level, the tumor grading and clinical stage of the patients. In conclusion, we suggest that Mo-MDSC should be considered as a potential therapy target in the course of prostate cancer treatment to enhance its anti-tumor effectiveness. [ABSTRACT FROM AUTHOR]

To see the frequency of prostatic malignancy in patients presenting with clinically benign prostate. Study Design: Descriptive case series. Setting: Department of Urology at Peoples University of Medical and Health Sciences for Women / Hospital Nawabshah. Period: Fifteen Months, From October 2016 to December 2017. Materials and Methods: A total of 100 patients who presented with the clinically benign prostate in Urology OPD were enrolled. All concern data regarding Age, mode of presentation (lower urinary tract symptoms with IPSS score/Acute retention of urine), comorbid, clinical examination findings, pre voided and post-void residual urine determination (on ultrasonography) were entered. The laboratory investigation includes complete blood count, urea, creatinine, random blood sugar (RBS), urine DR and CS, coagulation profile were performed before TURP.TURP performed under spinal anesthesia. After TURP the prostatic tissue chips were sent for histopathology as a routine. Data was analyzed through SPSS Version 20.0. Results: The average age of males was 71.38± 7.19 yrs. Most of the patients with (IPSS 20-35) BPH have lower urinary tract symptoms (both obstructive and irritative). DRE was done in all patients to estimate the size of the prostrate, it was varying from grade 1 enlarged n= 27(27%), grade 2 enlarged n= 36(36%), to grade 3 enlarged in n=37(37%). There were 3 (3%) cases reported to have prostate cancer, with findings confirmed by biopsy of TURP Specimen. There was no mortality seen in our study. The clinical presentation of patients, grades of enlargements on DRE and IPSS however, demonstrated no correlation. Conclusion: BPH is more common between 60-80yrs. When patient undergo TURP or open prostatectomy, every specimen should be sent for biopsy because prostate cancer is only confirmed by biopsy, so that prostate cancer is detected early Radiology & PSA values are supportive in their role but are not true diagnostic. Prostatic cancer is a significant morbid condition, so effective measures should be taken to detect prostatic cancer, so that patient can be properly treated according to the stage. [ABSTRACT FROM AUTHOR]

Seung Chol Park,1 Yu Seob Shin,2 Li Tao Zhang,2 Dal Sik Kim,3 Sung Zoo Kim,4 Nam Cheol Park,5 Tai Young Ahn,6 Je Jong Kim,7 Sung Won Lee,8 Insuk So,9 Jong Kwan Park2,10,11 1Department of Urology, Wonkwang University School of Medicine and Hospital, Iksan, South Korea; 2Department of Urology, 3Department of Laboratory Medicine, 4Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju, 5Department of Urology, College of Medicine, Pusan National University Hospital, Busan, 6Department of Urology, College of Medicine, Ulsan University, Seoul, 7Department of Urology, College of Medicine, Korea University, Seoul, 8Department of Urology, Samsung Medical Center, College of Medicine, SungKyunkwan University, Seoul, 9Department of Physiology, College of Medicine, Seoul National University, Seoul, 10Research Institute of Clinical Medicine, Chonbuk National University, 11Biomedical Research Institute and Clinical Trial Center, Chonbuk National University Hospital, Jeonju, South KoreaPurpose: Prostate-specific antigen (PSA) is the most important marker in the diagnosis and follow-up of patients with prostate cancer. The primary objective of this study was to evaluate the effect of various urologic procedures in prostatic area on serum free and total PSA levels.Subjects and methods: A series of 62 patients (8 after digital rectal examination [DRE], 12 after transrectal ultrasonography [TRUS], 11 after rigid cystoscopy, 13 after prostatic massage, 8 after TRUS-guided prostate biopsy, and 10 after transurethral resection of prostate [TURP]) were enrolled in the study. Blood samples were taken from each patient before procedure and at 10, 30, 60, and 120 minutes after procedures.Results: Prostate massage, rigid cystoscopy, TURP, and TRUS-guided prostate biopsy caused statistically significant rise in total and free PSA levels in the serum. There was no significant increase in total and free PSA levels in the serum after DRE and TRUS. The mean differences were greater for free PSA level in the serum for TURP, TRUS-guided prostate biopsy, prostate massage, and rigid cystoscopy.Conclusion: Total and free PSA levels in the serum are altered by prostate massage, rigid cystoscopy, TRUS-guided prostate biopsy, and TURP. The PSA rises were related to the stimulation strength of the procedures. The total and free PSA levels were increased significantly from 10 minutes after procedures, except DRE and TRUS, and were increased to maximal level at 60 minutes after procedures.Keywords: prostate specific antigen (PSA), marker, diagnosis, prostate cancer, urologic procedures

This paper reports the development of an easy to use antibody microarray-based immunoassay platform for sensitive and selective duplex detection of PSA (prostate specific antigen) and hK2 (human kallikrein 2). Using PDMS wells in a 3 × 9 array on epoxy-coated glass slides 27 duplex immunoassays can be performed in parallel. Automated microarraying provided fast and reproducible antibody arraying in each assay well. To achieve highly sensitive and selective detection of each biomarker, we evaluated and optimized the density of each of the immobilized capture antibodies. The assay platform showed a limit of detection (LOD) of each biomarker (PSA and hK2) of less than 10 pg/mL and a dynamic range of 104–105 orders of magnitude. Neither the PSA nor the hK2 antibody array showed any cross-reaction against each others target proteins or other plasma proteins. These results emphasize the importance of density optimization of capture antibody on the surface in order to achieve a sensitive and selective multiplex immunoassay.

Background: Prostate-specific antigen (PSA) levels are influenced by genetic variation unrelated to prostate cancer risk. Whether a genetic predisposition to a higher PSA level predisposes to a diagnostic work-up for prostate cancer is not known., Methods: Participants were 3110 men of African and European ancestries ages 45-70, without prostate cancer and with a baseline PSA < 4 ng/mL, undergoing routine clinical PSA screening. The exposure was a polygenic score (PGS) comprising 111 single nucleotide polymorphisms associated with PSA level, but not prostate cancer. We tested whether the PGS was associated with a: 1) PSA value > 4 ng/mL, 2) International Classification of Diseases (ICD) code for an elevated PSA, 3) encounter with a urologist, or 4) prostate biopsy. Multivariable Cox proportional hazards models were adjusted for age and genetic principal components. Analyses were stratified by age (45-59 years, and 60-70 years old). Association estimates are per standard deviation change in the PGS., Findings: The median age was 56.6 years, and 2118 (68%) participants were 45-59 years. The median (IQR) baseline PSA level was 1.0 (0.6-1.7) ng/mL. Among men ages 45-59, the PGS was associated with a PSA > 4 (hazard ratio [HR] = 1.35 [95% CI, 1.17-1.57], p = 4.5 × 10 -5 ), an ICD code for elevated PSA (HR = 1.30 [1.12-1.52], p = 8.0 × 10 -4 ), a urological evaluation (HR = 1.34 [1.14-1.57], p = 4.8 × 10 -4 ), and undergoing a prostate biopsy (HR = 1.35 [1.11-1.64], p = 0.002). Among men ages 60-70, association effect sizes were smaller and not significant., Interpretation: A predisposition toward higher PSA levels was associated with clinical evaluations of an elevated PSA among men ages 45-59 years., Funding: National Institutes of Health (NIH)., Competing Interests: Declaration of interests JJT holds minor equity in and has received consulting fees from LynxDx. JSW receives additional funding from the National Institutes of Health (U01CA261339). The remaining authors have no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Abstract An aptasensor with guanine chemiluminescence detection was developed for the early diagnosis of prostate cancer with the simultaneous quantifications of prostate specific antigen (PSA) and vascular endothelial growth factor (VEGF). A PSA DNA aptamer conjugated with Texas Red emits red light in guanine chemiluminescence reaction, whereas a VEGF DNA aptamer conjugated with 6-FAM emits green light. The PSA and VEGF aptamers immobilized on the surface of paramagnetic beads mixed with a sample were incubated for 30 min. After the incubation, PSA and VEGF bound with PSA and VEGF aptamers were simultaneously quantified for 20 s using guanine chemiluminescence detections operated with two photomultiplier tubes and two optical filters capable of selectively collecting green or red light. With the increase of PSA concentration, the strength of the red light emitted from Texas Red dropped exponentially, whereas with the increase of VEGF concentration, the green light emitted from 6-FAM was enhanced. The limits of detection were as low as 0.6 ng/ml for PSA and 0.4 ng/ml for VEGF. We confirmed that the dual-aptasensor can be applied as an advanced and new medical device capable of simultaneously quantifying PSA and VEGF to early diagnose prostate cancer with good accuracy, precision, and reproducibility. Graphical abstract Image 1 Highlights • Intra chemiluminescence (CL) resonance energy transfer in guanine CL reaction of high-energy intermediate and luminophore. • Application of Intra chemiluminescence resonance energy transfer to simultaneously quantify PSA and VEGF in a sample. • Development of a highly sensitive and selective aptasensor for the early diagnosis of prostate cancer. [ABSTRACT FROM AUTHOR]

Emetine is a small molecule protein synthesis inhibitor that is toxic to all cell types and therefore suitable for complete killing of all types of heterogeneous cancer cells within a tumor. It becomes significantly inactive (non-toxic) when derivatized at its N-2′ secondary amine. This provides a strategy for targeting emetine to cancerous tumor without killing normal cells. In this report, PSA activatable peptide prodrugs of emetine were synthesized. To overcome steric hindrances and enhance protease specific cleavage, a 2-stage prodrug activation process was needed to release emetine in cancer cells. In this 2-stage process, emetine prodrug intermediates are coupled to PSA peptide substrate (Ac-His-Ser-Ser-Lys-Leu-Gln) to obtain the full prodrug. Both prodrug intermediates 10 (Ala-Pro-PABC-Emetine) and 14 (Ser-Leu-PABC-Emetine) were evaluated for kinetics of hydrolysis to emetine and potency [Where PABC =  p -aminobenzyloxycarbonyl]. While both intermediates quantitatively liberate emetine when incubated under appropriate conditions, upon coupling of PSA substrate to give the full prodrugs, only prodrug 16 , the prodrug obtained from 14 was hydrolyzable by PSA. Cytotoxicity studies in PSA producing LNCaP and CWR22Rv1 confirm the activation of the prodrug by PSA with an IC 50 of 75 nM and 59 nM respectively. The cytotoxicity of 16 is significantly reduced in cell lines that do not produce PSA. Further, in vivo toxicity studies are done on these prodrugs and other derivatives of emetine. The results show the significance of conformational modulation in obtaining safe emetine prodrugs. [ABSTRACT FROM AUTHOR]

The development of a disposable immunosensor based on a hybrid goldcarbon screen-printed electrode array is described. The electrodeposition of gold is shown to lead to a field of nanocrystals that facilitates antibody immobilization and enhances electron transfer. A label-free analysis protocol based on ferrocyanide has been developed for the detection of Prostate Specific Antigen in the fgmL-1 range. [ABSTRACT FROM AUTHOR]

This work reports a novel colorimetric immunoassay for ultrasensitive quantitation of prostate specific antigen (PSA) based on glucose oxidase (GOx) catalyzed cascade formation of blue-black iodine–starch complex. In this design, a potassium iodide (KI)–starch system was integrated with a sandwich immunoassay, multivalent biotin–avidin interaction and high efficient GOx catalysis. In the presence of PSA, biotinylated anti–PSA and GOx–conjugated avidin was successively introduced via the specific immunobinding and the high affinity biotin–avidin interaction. GOx–catalyzed oxidation of glucose leads to cascade production of gluconic acid and hydrogen peroxide (H 2 O 2 ), which subsequently oxidizes KI and results in a visual color change of the starch solution due to the formation of an intense colored iodine–starch complex. The color intensity is proportional to the analyte level, allowing a simple and rapid assay by direct readout with naked eyes. A quantitative immunoassay is easily accomplished by an UV–vis spectrophotometer. Under optimal condition, a colorimetric immunoassay with an ultralow limit of detection (LOD) at 0.46 pg mL −1 and a wide dynamic range from 1 pg mL −1 to 1 μg mL −1 was achieved with PSA as a model biomarker, demonstrating its great potential for early cancer diagnosis in clinical application. [ABSTRACT FROM AUTHOR]