The first reported values of microplastics in prostate.

BACKGROUND: Microplastics are ubiquitous, widespread environmental pollutants with unavoidable human exposure. Herein, it was aimed to investigate the presence of microplastics in prostate tissue. METHODS: Prostate tissues from 12 patients who underwent Trans Urethral Resection of the Prostate (TUR-P) were analyzed to investigate the presence of microplastics. Initially, the prostate tissues were analyzed for microplastic particles using a light microscope after extraction. Subsequently, the chemical composition of the particles found in the prostate tissues was characterized using Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectrophotometry. RESULTS: Microplastic particles of various types were detected in 6 out of 12 patients. All detected plastic particles in this study were microplastics, with sizes below 26 µm in size. These microplastics exhibited different shapes as pellets, spheres or fibers. Overall, among the 12 analyzed prostate tissue samples, four different types of plastic were identified in six samples. The most common type of microplastic detected was Polyamide (Nylon 6), found in samples from three patients. Other detected types, Polypropylene, Polyacrylic Acid and Poly (dimethylsiloxane) were each determined in samples from one patient. CONCLUSIONS: This is the first study to demonstrate the presence of microplastics in prostate tissue, serving as an exploratory investigation, which can trigger further research to validate the results in a larger patient cohort.

The sensor applications for prostate and lung cancer biomarkers in terms of electrochemical analysis.

Prostate and lung cancers are the most common types of cancer and affect a large part of the population around the world, causing deaths. Therefore, the rapid identification of cancer can profoundly impact reducing cancer-related death rates and protecting human lives. Significant resources have been dedicated to investigating new methods for early disease detection. Cancer biomarkers encompass various biochemical entities, including nucleic acids, proteins, sugars, small metabolites, cytogenetic and cytokinetic parameters, and whole tumor cells in bodily fluids. These tools can be utilized for various purposes, such as risk assessment, diagnosis, prognosis, treatment efficacy, toxicity evaluation, and predicting a return. Due to these versatile and critical purposes, there are widespread studies on the development of new, sensitive, and selective approaches for the determination of cancer biomarkers. This review illustrates the significant lung and prostate cancer biomarkers and their determination utilizing electrochemical sensors, which have the advantage of improved sensitivity, low cost, and simple analysis. Additionally, approaches such as improving sensitivity with nanomaterials and ensuring selectivity with MIPs are used to increase the performance of the sensor. This review aims to overview the most recent electrochemical biosensor applications for determining vital biomarkers of prostate and lung cancers in terms of nanobiosensors and molecularly imprinted polymer (MIP)-based biosensors.

Bio-conjugated carbon dots for the bimodal detection of prostate cancer biomarkers via sandwich fluorescence and electrochemical immunoassays.

Bimodal detection facilitates the accurate and reliable detection of cancer biomarkers, which can assist in the early diagnosis of cancer. Herein, S-doped carbon dots (OCDs) with a size of 3 nm and blue emission were synthesized by the hydrothermal treatment of onion extract. The S-doped carbon dots were bioconjugated with an antibody (OCDs@PSAAbHRP) to design a nanoprobe for the detection of prostate specific antigen (PSA), an important serum based prostate cancer biomarker. The detection probe enabled the biomodal assay of PSA via fluorescence immunoassay (FIA) and electrochemical immunoassay (ECIA). In both assays, polyethylenimine stabilized polyaniline nanoparticles (PNPs) were used as the immobilization matrix, which played a major role in widening the linear range of biosensors (0.1 to 100 ng ml-1 for ECIA and 5 to 120 ng ml-1 for FIA). Paper-based and smartphone-integrated fluorescence immuno-array developed using the OCDs@PSAAbHRP detection probe provided cost-effective and rapid detection, while the electrochemical immunoassay provided a high sensitivity (7.8 µA ng-1 ml-1 cm-2) and low detection limit (38 pg ml-1) for PSA detection. The role of OCDs in enhancing the sensor performance was deciphered by carrying out detailed electrochemical studies with HRP enzyme-loaded OCDs. The biosensor was used to detect PSA in human blood serum samples and the results were consistent with conventional techniques. Owing to its analytical properties coupled with simplicity, cost-effectiveness, and portability, the bimodal sensor system has potential for application in clinical analysis.

SERS-Temperature Dual-Mode T-type Lateral Flow Strip for Accurate Detection of Free and Total Prostate-Specific Antigens in Blood.

Accurate point-of-care (POC) analysis of cancer markers is the essence in the comprehensive early screening and treatment of cancer. Dual-mode synchronous detection is one of the effective approaches to reduce the probability of false negatives or false positives. As a result, this can greatly improve the accuracy of diagnosis. In this work, a surface-enhanced Raman scattering (SERS)-temperature dual-mode T-type lateral flow strip was fabricated to direct and simultaneous POC detection of total and free prostate-specific antigens (t-PSA and f-PSA) in blood. With the advantage of high stability of T-type lateral flow strip and simultaneous acquirement of assay results for t-PSA and f:t PSA ratio, the proposed method has high accuracy in the diagnosis of prostate cancer, especially in the diagnostic gray zone between 4.0 and 10.0 ng/mL. The SERS-temperature dual-signal has a good linear correlation with either f-PSA or t-PSA. To evaluate the clinical diagnostic performance of the proposed method, spiked human serum samples and the whole blood sample were analyzed. The assay results showed good recovery, and compared with traditional electrochemiluminescence immunoassay (ECLIA) method (t-PSA: 43.151; f/t ratio: 0.08), the results obtained by the proposed method were similar (t-PSA: 40.15 (SERS), 36.21 (temperature); f/t ratio: 0.08 (SERS), 0.08 (temperature), but the detection time (15 min) and cost ($0.05) had been greatly reduced. Therefore, the proposed SERS-temperature synchronous dual-mode T-type lateral flow strip has a strong application potential in the field of accurate large-scale diagnostics of prostate cancer on-site by simultaneous POC detection of t-PSA and f-PSA in blood.

Endocrine Disruptors and Estrogens in Human Prostatic Tissue.

Endocrine disruptors (EDs) are ubiquitous substances both in the environment and everyday products that interfere with the hormonal system. Growing evidence demonstrates their adverse effects on the organism, including the reproductive system and the prostate, owing to their (anti)estrogenic or antiandrogenic effects. Since EDs can interact with steroid hormone actions on-site, understanding the levels of intraprostatic EDs in conjunction with steroids may hold particular significance. The aim of this study was to develop and validate a method for determining estrogens, various groups of EDs (bisphenols, parabens, oxybenzone and nonylphenol) and phytoestrogens in their unconjugated and conjugated forms in prostate tissue by liquid chromatography-tandem mass spectrometry, and subsequently analyze 20 human prostate tissue samples. The method enabled 20 compounds to be analyzed: estrogens (estrone, estradiol, estriol), bisphenols (bisphenol A- BPA, BPS, BPF, BPAF, BPAP, BPZ, BPP), parabens (methyl-, ethyl-, propyl-, butyl-, benzyl- paraben), oxybenzone, nonylphenol and phytoestrogens (daidzein, genistein, equol) with LLOQs between 0.017-2.86 pg/mg of tissue. The most frequently detected EDs in prostate tissues were propylparaben (conjugated and unconjugated forms in 100 % of tissues), methylparaben (unconjugated in 45 % and conjugated in 100 %), ethylparaben (unconjugated in 25 % and conjugated in 100 % BPA (unconjugated in 35 % and conjugated in 60 % and oxybenzone (both forms in 45 % To the best of our knowledge, this is the first study detecting EDs, phytoestrogens and estriol conjugate (E3C) in the prostate. E3C was the most abundant estrogen in prostatic tissue. This highlights the need for further explorations into estrogen metabolism within the prostate.

The dark side of lipid metabolism in prostate and renal carcinoma: novel insights into molecular diagnostic and biomarker discovery.

INTRODUCTION: Lipidomics focuses on the in-depth analysis of lipids, which are crucial macromolecules involved in a wide range of metabolic pathways. The increased intracellular accumulation of different classes of lipids in renal cell carcinoma (RCC) and prostate cancer (PCa) cells may be caused by elevated absorption or by increased de novo lipogenesis as a consequence of lipid metabolism reprogramming. The involvement of cholesterol metabolism in cancer's aberrant pathways has also been demonstrated. AREAS COVERED: This review provides an update on the most important lipidomics studies and applications in RCC and PCa, with a particular focus on how knowledge of aberrant lipid pathways may be used to identify biomarkers and novel therapeutic targets. In addition, the application of this methodologies have led to novel cancer subtypes identification and patient's risk stratification. Tracking tumor progression using specific biofluid metabolite profiles offers a huge translational opportunity for urological malignancies. EXPERT OPINION: Lipidomics is a promising branch of 'omics' approach and should include in next decade new standardized analysis methods and randomized clinical trials in order to reach the aim to use this high-throughput technique in patient-tailored therapy perspective.

Stokes shift spectroscopy and machine learning for label-free human prostate cancer detection.

The Stokes shift spectra (S3) of human cancerous and normal prostate tissues were collected label free at a selected wavelength interval of 40 nm to investigate the efficacy of the approach based on three key molecules-tryptophan, collagen, and reduced nicotinamide adenine dinucleotide (NADH)-as cancer biomarkers. S3 combines both fluorescence and absorption spectra in one scan. The S3 spectra were analyzed using machine learning (ML) algorithms, including principal component analysis (PCA), nonnegative matrix factorization (NMF), and support vector machines (SVMs). The components retrieved from the S3 spectra were considered principal biomarkers. The differences in the weights of the components between the two types of tissues were found to be significant. Sensitivity, specificity, and accuracy were calculated to evaluate the performance of SVM classification. This research demonstrates that S3 spectroscopy is effective for detecting the changes in the relative concentrations of the endogenous fluorophores in tissues due to the development of cancer label free.

Untargeted metabolomics reveals alterations in the metabolic reprogramming of prostate cancer cells by double-stranded DNA-modified gold nanoparticles.

Metabolic reprogramming plays an important role in the development of prostate cancer (PCa). However, there are few reports on the effects of nanomaterials as vectors on cancer metabolic reprogramming. Herein, a type of nanoparticle with good biocompatibility was synthesized by modifying the double-stranded of DNA containing a sulfhydryl group on the surface of gold nanoparticles (AuNPs-dsDNA) through salt-aging conjugation methods. The resultant AuNPs-dsDNA complexes possessed low toxicity to PC3 and DU145 cells in vitro. There was also no obvious hepatorenal toxicity after intravenous injection of AuNPs-dsDNA complexes in vivo, which indicated that these nanoparticles had good biological compatibilities. We investigated their biological functions using prostate cancer cells. Seahorse assay showed that AuNPs-dsDNA complexes could increase glycolysis and glycolysis capacity both in PC3 and DU145 cells. We further detected the expression of glycolysis-related genes by qPCR assay, and found that PKM2, PDHA, and LDHA were significantly upregulated. Furthermore, untargeted metabolomics revealed that PC (18:2(9Z,12Z)/18:2(9Z,12Z)) and PC (18:0/18:2 (9Z,12Z)) levels were decreased and inosinic acid level was increased in PC3 cells. Whereas (3S,6E,10E)-1,6,10,14-Phytatetraen-3-ol, Plasmenyl-PE 36:5 and Cer (d18:2/18:2) were decreased, PE 21:3 and 1-pyrrolidinecarboxaldehyde were increased in DU145 cells after co-culturing with AuNPs-dsDNA. In summary, we found that AuNPs and AuNPs-dsDNA complexes possibly regulate the metabolic reprogramming of cancer cells mainly through the lipid metabolic pathways, which could compensate for the previously mentioned phenomenon of enhanced glycolysis and glycolysis capacity. This will provide an important theoretical basis for our future research on the characteristic targeted design of nanomaterials for cancer metabolism.

The relationship between prostatic microvessel density and different concentrations of oestrogen/androgen in Sprague-Dawley rats.

BACKGROUND: Currently, there are relatively few studies on the effects of changes in oestrogen and androgen levels on prostatic microvessel density (MVD). This article aimed to study the changes in prostatic MVD in Sprague-Dawley (SD) rats after castration under the effect of oestrogen/androgen at different concentrations. METHODS: Male SD rats aged 3-4 months were randomly divided into a control group, a castration group, and groups with different concentrations of oestrogen/androgen treatment after castration. Dihydrotestosterone (DHT) and oestradiol (E) were administered daily by subcutaneous injection for one month. All the rats were killed by cervical dislocation after one month, and the serum DHT and E concentrations of the rats in each group were measured by ELISA. Prostate tissue specimens were immunohistochemically stained with monoclonal antibodies against CD34 and factor VIII for MVD. RESULTS: Compared with the control group, the MVD decreased significantly in the castration group (P < 0.05). When the exogenous E concentration was constant, in general, the MVD of rats in all the groups increased with increasing exogenous DHT concentration. Compared with the castration group, the MVD increased significantly in the E0.05 + DHT0.015 mg/kg, E0.05 + DHT0.05 mg/kg, E0.05 + DHT0.15 mg/kg, E0.05 + DHT0.5 mg/kg, and E0.05 + DHT1.5 mg/kg groups (P < 0.05). In addition, when the exogenous DHT concentration was constant, the MVD increased with increasing exogenous E concentration in all the groups. Among them, compared with the control and castration groups, the MVD increased significantly in the DHT0.15 + E0.015 mg/kg, DHT0.15 + E0.15 mg/kg, and DHT0.15 + E0.5 mg/kg groups (P < 0.05). CONCLUSIONS: Androgens play an important role in the regulation of prostatic MVD in SD rats, and a decrease in DHT concentration can induce a decrease in prostatic MVD. In contrast, prostatic MVD can be increased with increasing DHT concentration. In addition, prostatic MVD can be increased gradually with increasing oestrogen concentration.

Label-Free Imaging of Lipid Droplets in Prostate Cells Using Stimulated Raman Scattering Microscopy and Multivariate Analysis.

Hyperspectral stimulated Raman scattering (SRS) microscopy is a powerful imaging modality for the analysis of biological systems. Here, we report the application of k-means cluster analysis (KMCA) of multi-wavelength SRS images in the high-wavenumber region of the Raman spectrum as a robust and reliable method for the segmentation of cellular organelles based on the intrinsic SRS spectrum. KMCA has been applied to the study of the endogenous lipid biochemistry of prostate cancer and prostate healthy cell models, while the corresponding SRS spectrum of the lipid droplet (LD) cluster enabled direct comparison of their composition. The application of KMCA in visualizing the LD content of prostate cell models following the inhibition of de novo lipid synthesis (DNL) using the acetyl-coA carboxylase inhibitor, 5-(tetradecyloxy)-2-furoic acid (TOFA), is demonstrated. This method identified a reliance of prostate cancer cell models upon DNL for metabolic requirements, with a significant reduction in the cellular LD content after treatment with TOFA, which was not observed in normal prostate cell models. SRS imaging combined with KMCA is a robust method for investigating drug-cell interactions in a label-free manner.

Prostate MRI percentage tumor involvement or "PI-RADS percent" as a predictor of adverse surgical pathology.

BACKGROUND: This study assesses magnetic resonance imaging (MRI) prostate % tumor involvement or "PI-RADs percent" as a predictor of adverse pathology (AP) after surgery for localized prostate cancer (PCa). Two separate variables, "All PI-RADS percent" (APP) and "Highest PI-RADS percent" (HPP), are defined as the volume of All PI-RADS 3-5 score lesions on MRI and the volume of the Highest PI-RADS 3-5 score lesion each divided by TPV, respectively. METHOD: An analysis was done of an IRB approved prospective cohort of 557 patients with localized PCa who had targeted biopsy of MRI PIRADs 3-5 lesions followed by RARP from April 2015 to May 2020 performed by a single surgeon at a single center. AP was defined as ISUP GGG ≥3, pT stage ≥T3 and/or LNI. Univariate and multivariable analyses were used to evaluate APP and HPP at predicting AP with other clinical variables such as Age, PSA at surgery, Race, Biopsy GGG, mpMRI ECE and mpMRI SVI. Internal and External Validation demonstrated predicted probabilities versus observed probabilities. RESULTS: AP was reported in 44.5% (n = 248) of patients. Multivariable regression showed both APP (odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.04-1.14, p = 0.0007) and HPP (OR: 1.10; 95% CI: 1.04-1.16; p = 0.0007) were significantly associated with AP with individual area under the operating curves (AUCs) of 0.6142 and 0.6229, respectively, and AUCs of 0.8129 and 0.8124 when incorporated in models including preoperative PSA and highest biopsy GGG. CONCLUSIONS: Increasing PI-RADS Percent was associated with a higher risk of AP, and both APP and HPP may have clinical utility as predictors of AP in GGG 1 and 2 patients being considered for AS. PATIENT SUMMARY: Using PIRADs percent to predict AP for presurgical patients may help risk stratification, and for low and low volume intermediate risk patients, may influence treatment decisions.

Bipolar Electrode Array for Multiplexed Detection of Prostate Cancer Biomarkers.

Owing to the characteristics of high throughput, high flexibility, and convenient separation of the sensing and reporting reactions, the bipolar electrode (BPE) shows great potential in clinical analysis. However, there are some difficulties in the combination of BPEs and multiplex electrochemiluminescence (ECL) biosensing, such as the need for small sample consumption, multistep operations, and separated sample loading. In this paper, a microfluidic BPE array chip was fabricated toward multiplex detection of cancer biomarkers. With a special channel structure and the difference in flow resistance of channels of different sizes, the direction of liquid flow was successfully controlled. In this way, rapid and automatic multiplex sampling was achieved on the array, which would help improve the sensing efficiency and reduce the reagent consumption. The ECL BPE array chip served as an immunosensor for multiple prostate cancer biomarkers including prostate-specific antigen (PSA), interleukin-6 (IL-6), and prostate-specific membrane antigen (PSMA). The microfluidic BPE chip shows good reproducibility and high sensitivity. The limits of detection for PSA, IL-6, and PSMA are 0.093 ng/mL, 0.061 pg/mL, and 0.059 ng/mL, respectively. It also exhibits excellent performance in real sample analysis. The integrated ECL BPE array shows a good application prospect in clinical sensing of cancer biomarkers, as well as point-of-care testing.

Imbalance in the estrogen/androgen ratio may affect prostate fibrosis through the TGF-ß/Smad signaling pathway.

OBJECTIVE: The present study aimed to investigate the effects of an imbalance in the estrogen/androgen ratio on prostate fibrosis. METHODS: Different concentrations of dihydrotestosterone (DHT) or estradiol (E2) dissolved in corn oil were injected subcutaneously into the nape of the castrated Sprague-Dawley (SD) rats over 28 consecutive days. Masson's trichrome staining and immunohistochemical staining were performed to detect the content of collagen fibers and the expression of collagen I, fibronectin, and elastin in the rat prostate of each group, respectively. DHT + E2 at different concentrations was administered to human normal prostate stromal immortalized cells (WPMY-1 cells) for 1 week. The expression of collagen I, fibronectin, elastin, transforming growth factor-ß1 (TGF-ß1), Smad3, and Smad7 was detected by Western blotting (WB). Then, WPMY-1 cells treated with 10 nM DHT + 5 pM E2 were incubated with the TGF-ß/Smad pathway inhibitor SD208 for 1 week, after which collagen I, fibronectin, and elastin expression was detected by WB. RESULTS: Compared with the uncastrated control and corn oil injection groups, the collagen fiber content and collagen I and fibronectin expression were increased and elastin expression was decreased in the castrated rat prostate with corn oil injection group (p < 0.01). Compared to castrated corn oil injection group, collagen fiber content, collagen I, and fibronectin expression were significantly decreased, and elastin expression was significantly increased in the castrated rat prostate 0.15 mg/kg DHT treatment group (p < 0.01). Following treatment with 0.15 mg/kg DHT, the content of collagen fibers, and the expression of collagen I and fibronectin were increased, and the expression of elastin was decreased in the rat prostate with increasing concentrations of E2 treatment group compared to the 0.15 mg/kg DHT group (p < 0.05, p < 0.01). Following treatment with 0.05 mg/kg E2, the collagen fiber content and the expression of collagen I and fibronectin were decreased, and the expression of elastin was increased in the rat prostate with increasing DHT concentration treatment group compared to the 0.05 mg/kg E2 group (p < 0.05, p < 0.01). Compared with the Control group, the expression of collagen I, fibronectin, TGF-ß1 and Smad3 was decreased, and the expression of elastin and Smad7 was increased in WPMY-1 cells after treatment with 10 nM DHT (p < 0.01). Following treatment with 10 nM DHT, the expression of collagen I, fibronectin, TGF-ß1, and Smad3 was increased, and the expression of elastin and Smad7 was decreased in WPMY-1 cells with increasing E2 concentration treatment compared to the 10 nM DHT group (p < 0.05, p < 0.01). Following treatment with 5 pM E2, the expression of collagen I, fibronectin, TGF-ß1, and Smad3 was decreased, and elastin and Smad7 expression was increased with increasing DHT concentration compared to the 5 pM E2 group (p < 0.05, p < 0.01). Compared to the 10 nM DHT + 5 pM E2 group, the expressions of collagen I and fibronectin were decreased; the expression of elastin was increased in WPMY-1 cells after the supplement of TGF-ß/Smad pathway inhibitor SD208 group (p < 0.05, p < 0.01). CONCLUSIONS: An imbalance in the estrogen/androgen ratio may affect prostate fibrosis. E2 may activate the degree of prostate fibrosis. In contrast to the effect of E2, DHT may inhibit the degree of prostate fibrosis, which might involve the TGF-ß/Smad signaling pathway.

A mass spectrometric method for in-depth profiling of phosphoinositide regioisomers and their disease-associated regulation.

Phosphoinositides are a family of membrane lipids essential for many biological and pathological processes. Due to the existence of multiple phosphoinositide regioisomers and their low intracellular concentrations, profiling these lipids and linking a specific acyl variant to a change in biological state have been difficult. To enable the comprehensive analysis of phosphoinositide phosphorylation status and acyl chain identity, we develop PRMC-MS (Phosphoinositide Regioisomer Measurement by Chiral column chromatography and Mass Spectrometry). Using this method, we reveal a severe skewing in acyl chains in phosphoinositides in Pten-deficient prostate cancer tissues, extracellular mobilization of phosphoinositides upon expression of oncogenic PIK3CA, and a unique profile for exosomal phosphoinositides. Thus, our approach allows characterizing the dynamics of phosphoinositide acyl variants in intracellular and extracellular milieus.

TF-Marker: a comprehensive manually curated database for transcription factors and related markers in specific cell and tissue types in human.

Transcription factors (TFs) play key roles in biological processes and are usually used as cell markers. The emerging importance of TFs and related markers in identifying specific cell types in human diseases increases the need for a comprehensive collection of human TFs and related markers sets. Here, we developed the TF-Marker database (TF-Marker, http://bio.liclab.net/TF-Marker/), aiming to provide cell/tissue-specific TFs and related markers for human. By manually curating thousands of published literature, 5905 entries including information about TFs and related markers were classified into five types according to their functions: (i) TF: TFs which regulate expression of the markers; (ii) T Marker: markers which are regulated by the TF; (iii) I Marker: markers which influence the activity of TFs; (iv) TFMarker: TFs which play roles as markers and (v) TF Pmarker: TFs which play roles as potential markers. The 5905 entries of TF-Marker include 1316 TFs, 1092 T Markers, 473 I Markers, 1600 TFMarkers and 1424 TF Pmarkers, involving 383 cell types and 95 tissue types in human. TF-Marker further provides a user-friendly interface to browse, query and visualize the detailed information about TFs and related markers. We believe TF-Marker will become a valuable resource to understand the regulation patterns of different tissues and cells.

Mass Spectrometry Imaging of N-Linked Glycans in a Formalin-Fixed Paraffin-Embedded Human Prostate by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization.

N-Linked glycans are structurally diverse polysaccharides that represent significant biological relevance due to their involvement in disease progression and cancer. Due to their complex nature, N-linked glycans pose many analytical challenges requiring the continued development of analytical technologies. Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is a hybrid ionization technique commonly used for mass spectrometry imaging (MSI) applications. Previous work demonstrated IR-MALDESI to significantly preserve sialic acid containing N-linked glycans that otherwise require chemical derivatization prior to detection. Here, we demonstrate the first analysis of N-linked glycans in situ by IR-MALDESI MSI. A formalin-fixed paraffin-embedded human prostate tissue was analyzed in negative ionization mode after tissue washing, antigen retrieval, and pneumatic application of PNGase F for enzymatic digestion of N-linked glycans. Fifty-three N-linked glycans were confidently identified in the prostate sample where more than 60% contained sialic acid residues. This work demonstrates the first steps in N-linked glycan imaging of biological tissues by IR-MALDESI MSI. Raw data files are available in MassIVE (identifier: MSV000088414).

Extracellular Vesicle Proteome in Prostate Cancer: A Comparative Analysis of Mass Spectrometry Studies.

Molecular diagnostics based on discovery research holds the promise of improving screening methods for prostate cancer (PCa). Furthermore, the congregated information prompts the question whether the urinary extracellular vesicles (uEV) proteome has been thoroughly explored, especially at the proteome level. In fact, most extracellular vesicles (EV) based biomarker studies have mainly targeted plasma or serum. Therefore, in this study, we aim to inquire about possible strategies for urinary biomarker discovery particularly focused on the proteome of urine EVs. Proteomics data deposited in the PRIDE archive were reanalyzed to target identifications of potential PCa markers. Network analysis of the markers proposed by different prostate cancer studies revealed moderate overlap. The recent throughput improvements in mass spectrometry together with the network analysis performed in this study, suggest that a larger standardized cohort may provide potential biomarkers that are able to fully characterize the heterogeneity of PCa. According to our analysis PCa studies based on urinary EV proteome presents higher protein coverage compared to plasma, plasma EV, and voided urine proteome. This together with a direct interaction of the prostate gland and urethra makes uEVs an attractive option for protein biomarker studies. In addition, urinary proteome based PCa studies must also evaluate samples from bladder and renal cancers to assess specificity for PCa.

Urinary Volatiles and Chemical Characterisation for the Non-Invasive Detection of Prostate and Bladder Cancers.

Bladder cancer (BCa) and prostate cancer (PCa) are some of the most common cancers in the world. In both BCa and PCa, the diagnosis is often confirmed with an invasive technique that carries a risk to the patient. Consequently, a non-invasive diagnostic approach would be medically desirable and beneficial to the patient. The use of volatile organic compounds (VOCs) for disease diagnosis, including cancer, is a promising research area that could support the diagnosis process. In this study, we investigated the urinary VOC profiles in BCa, PCa patients and non-cancerous controls by using gas chromatography-ion mobility spectrometry (GC-IMS) and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) to analyse patient samples. GC-IMS separated BCa from PCa (area under the curve: AUC: 0.97 (0.93-1.00)), BCa vs. non-cancerous (AUC: 0.95 (0.90-0.99)) and PCa vs. non-cancerous (AUC: 0.89 (0.83-0.94)) whereas GC-TOF-MS differentiated BCa from PCa (AUC: 0.84 (0.73-0.93)), BCa vs. non-cancerous (AUC: 0.81 (0.70-0.90)) and PCa vs. non-cancerous (AUC: 0.94 (0.90-0.97)). According to our study, a total of 34 biomarkers were found using GC-TOF-MS data, of which 13 VOCs were associated with BCa, seven were associated with PCa, and 14 VOCs were found in the comparison of BCa and PCa.

Kinetic Studies of Newly Patented Aminoalkanol Derivatives with Potential Anticancer Activity as Competitive Inhibitors of Prostate Acid Phosphatase.

BACKGROUND: Acid phosphatase and its regulation are important objects of biological and clinical research and play an important role in the development and treatment of prostate and bone diseases. The newly patented aminoalkanol (4-[2-hydroxy-3-(propan-2-ylamino)propyl]-1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5,10-trione hydrochloride) (I) and (4-[3-(dimethylamino)-2-hydroxypropyl]-1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5,10-trione hydrochloride) (II) derivatives have potential anticancer activity, and their influence on enzymatic activity can significantly impact the therapeutic effects of acid phosphatase against many diseases. Therefore, in this study, we investigated the action of compounds (I) and (II) on acid phosphatase. METHODS: Capillary electrophoresis was used to evaluate the inhibition of acid phosphatase. Lineweaver-Burk plots were constructed to compare the Km of this enzyme in the presence of inhibitors (I) or (II) with the Km in solutions without these inhibitors. RESULTS: Compound (I) showed a stronger competitive inhibition against acid phosphatase, whereas derivative (II) showed a weaker competitive type of inhibition. The detailed kinetic studies of these compounds showed that their type and strength of inhibition as well as affinity depend on the kind of substituent occurring in the main chemical molecule. CONCLUSIONS: This study is of great importance because the disclosed inhibition of acid phosphatase by compounds (I) and (II) raises the question of whether these compounds could have any effect on the treatment possibilities of prostate diseases.

Establishment and prospective validation of an SUVmax cutoff value to discriminate clinically significant prostate cancer from benign prostate diseases in patients with suspected prostate cancer by 68Ga-PSMA PET/CT: a real-world study.

Background and Aims: The aims of this study were to establish a maximum standardized uptake value (SUVmax) cutoff to discriminate clinically significant prostate cancer (csPCa) from benign prostate disease (BPD) by 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) in patients with suspected prostate cancer (PCa), and to perform a prospective real-world validation of this cutoff value. Methods: The study included a training cohort to identify an SUVmax cutoff value and a prospective real-world cohort to validate it. A retrospective analysis assessed 135 patients with suspected PCa in a large tertiary care hospital in China who underwent 68Ga-PSMA-11 PET/CT. All patients were suspected of having PCa based on symptoms, digital rectal examination (DRE), total prostate-specific antigen (tPSA) level, and multiparameter magnetic resonance imaging (mpMRI). The 68Ga-PSMA PET/CT results were evaluated using histopathological results from transrectal ultrasound-guided 12-core biopsy with necessary targeted biopsy as references. Patients with Gleason scores (GS) ≥7 from the biopsy results were diagnosed with csPCa, and patients with negative biopsy and follow-up results were diagnosed with BPD. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal SUVmax cutoff value. The cutoff value was prospectively validated in 58 patients with suspected PCa. The diagnostic benefits of the cutoff value for clinical decision making were also evaluated. Results: According to ROC curve analysis, the most appropriate SUVmax cutoff value for discriminating csPCa from BPD was 5.30 (sensitivity, 85.85%; specificity, 86.21%; area under the curve [AUC], 0.893). The cutoff achieved a sensitivity of 83.33%, a specificity of 81.25%, a positive predictive value (PPV) of 92.11%, a negative predictive value (NPV) of 65.00%, and an accuracy of 82.76% in the prospective validation cohort. Metastases were used as an indicator to reduce false negative results in patients with SUVmax ≤ 5.30. In patients without metastases, an SUVmax value of 5.30 was also the best cutoff to diagnose localized csPCa (sensitivity, 80.43%; specificity, 86.21%; AUC, 0.852). The cutoff discriminated localized csPCa from BPD with a sensitivity of 76.19%, a specificity of 81.25%, a PPV of 84.21%, an NPV of 72.22%, and an accuracy of 78.38% in the prospective validation cohort. The cutoff, combined with metastases, achieved an accuracy of 89.12% in all patients, increasing accuracy by 8.29% and reducing equivocal results compared with manual reading. There was a strong correlation between SUVmax and PSMA expression (rs = 0.831, P < 0.001) and a moderate correlation between SUVmax and GS (rs = 0.509, P < 0.001). The PSMA expression and SUVmax values of patients with csPCa were significantly higher than those of patients with BPD (P < 0.001). Conclusion: We established and prospectively validated the best SUVmax cutoff value (5.30) for discriminating csPCa from BPD with high accuracy in patients with suspected PCa. 5.30 is an effective cutoff to discriminate csPCa patients with or without metastases. The cutoff may provide a potential tool for the precise identification of csPCa by 68Ga-PSMA PET/CT, ensuring high accuracy and reducing equivocal results.