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Background: Although microbiota in prostatic tissues of patients with prostate cancer have been studied, results of different studies have been inconsistent. Different ethnicity of study subjects, different study designs, and potential contaminations during sample collection and experiments might have influenced microbiome results of prostatic tissues. In this study, we analyzed microbiota and their potential functions in benign and malignant tissues of prostate cancer considering possible contaminants and host variables. Materials and methods: A total of 118 tissue samples (59 benign tissues and 59 malignant tissues) obtained by robot‐assisted laparoscopic radical prostatectomy were analyzed and 64 negative controls (from sampling to sequencing processes) were included to reduce potential contaminants. Results: Alteration of the microbiome in prostate tissues was detected only in patients with diabetes. Furthermore, the influence of diabetes on microbiome was significant in malignant tissues. The microbiome in malignant tissues of patients with diabetes was influenced by pathologic stages. The relative abundance of Cutibacterium was reduced in the high pathologic group compared to that in the intermediate group. This reduction was related to microbial pathways increased in the high pathologic group. Conclusion: Results of this study indicate that diabetes can influence the progression of prostate cancer with microbiome alteration in prostate tissues. Although further studies are necessary to confirm findings of this study, this study can help us understand tissue microbiome in prostate cancer and improve clinical therapy strategies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Human prostatic tissue exhibits complex mechanical behaviour due to its multiphasic, heterogeneous nature, with hierarchical microstructures involving epithelial compartments, acinar lumens and stromal tissue all interconnected in complex networks. This study aims to establish a computational homogenization framework for quantifying the mechanical behaviour of prostate tissue, considering its multiphasic heterogeneous microstructures and the mechanical characteristics of tissue constituents. Representative tissue microstructure models were reconstructed from high‐resolution histology images. Parametric studies on the mechanical properties of the tissue constituents, particularly the fibre‐reinforced hyper‐elasticity of the stromal tissue, were carried out to investigate their effects on the apparent tissue properties. These were then benchmarked against the experimental data reported in literature. Results showed significant anisotropy, both structural and mechanical, and tension‐compression asymmetry of the apparent behaviours of the prostatic tissue. Strong correlation with the key microstructural indices such as area fractions of tissue constituents and the tissue fabric tensor was also observed. The correlation between the stromal tissue orientation and the principal directions of the apparent properties suggested an essential role of stromal tissue in determining the directions of anisotropy and the compression‐tension asymmetry characteristics in normal human prostatic tissue. This work presented a homogenization and histology‐based computational approach to characterize the apparent mechanical behaviours of human prostatic or other similar glandular tissues, with the ultimate aim of assessing how pathological conditions (e.g., prostate cancer and benign prostatic hyperplasia) could affect the tissue mechanical properties in a future study. [ABSTRACT FROM AUTHOR]

Introduction: Cell-cell communication is an important process in healthy tissue but also gains enhanced attention regarding pathological tissue. To date, the tumor microenvironment is gradually brought into focus when studying tumorigenesis. In the prostate gland, stromal and epithelial cells greatly interact to maintain homeostasis or tissue integrity. This study focuses on an indirect communication via soluble factors. Methods: To investigate the cell-cell interaction via soluble factors, the prostate carcinoma cell line LNCaP and the stromal primary cells p21 were co-cultured without direct contact and RNA was isolated at defined time points. Differences in gene expression were finally analyzed by RNA sequencing. Results: RNA sequencing revealed a time-depending differential expression profile. Selected factors were subsequently characterized at molecular level and analyzed in human prostate tissue of different developmental stages as well as pathology. GALNT14 was one of the highest induced co-culture-specific genes in LNCaP cells. Detection in healthy tissue and BPH revealed an agedependent decrease in GALNT14 expression. Moreover, in prostate carcinoma, GALNT14 expression heavily varied independent of the Gleason score. Conclusion: Overall, this work provides a basis for further studies related to paracrine stromal-epithelial interaction in prostate carcinoma and highlights the importance of GALNT14. [ABSTRACT FROM AUTHOR]

Gal-3 plays an important role in cell survival, mRNA splicing, and cell–cell and cell–matrix interactions. Depending on its cellular localization and cancer type, Gal-3 may have tumour-suppressive or tumour-promoting activities. Given the promising diagnostic role of Gal-3 in the urine of PCa patients found in our previous study, its concordant gene and protein expression levels, and its involvement in PCa-related biological processes (e.g., morphogenesis of the prostate gland epithelium), we aimed to investigate this protein immunohistochemically in tumour and normal prostate tissues. Gal-3 protein expression was evaluated in 48 tumour prostate tissues, eight normal prostate tissues and 14 adjacent-normal prostate tissues. Decreased Gal-3 staining was detected in tumour tissues compared with normal tissues. Although Gal-3 staining was decreased in tumour tissues with GS 5-8 and pT2 and pT3 stages compared with normal prostate tissue, no correlation was found between Gal-3 expression and PCa progression. In the present study, the pattern of cellular localization differed between groups, as Gal-3 was predominantly excluded from the nucleus in tumour tissues. Furthermore, Gal-3 had no significant effect on survival and relapse in these PCa patients. This work confirms Gal-3 as a promising marker for PCa diagnosis.

IntroductionCell-cell communication is an important process in healthy tissue but also gains enhanced attention regarding pathological tissue. To date, the tumor microenvironment is gradually brought into focus when studying tumorigenesis. In the prostate gland, stromal and epithelial cells greatly interact to maintain homeostasis or tissue integrity. This study focuses on an indirect communication via soluble factors.MethodsTo investigate the cell-cell interaction via soluble factors, the prostate carcinoma cell line LNCaP and the stromal primary cells p21 were co-cultured without direct contact and RNA was isolated at defined time points. Differences in gene expression were finally analyzed by RNA sequencing.ResultsRNA sequencing revealed a time-depending differential expression profile. Selected factors were subsequently characterized at molecular level and analyzed in human prostate tissue of different developmental stages as well as pathology. GALNT14 was one of the highest induced co-culture-specific genes in LNCaP cells. Detection in healthy tissue and BPH revealed an age-dependent decrease in GALNT14 expression. Moreover, in prostate carcinoma, GALNT14 expression heavily varied independent of the Gleason score.ConclusionOverall, this work provides a basis for further studies related to paracrine stromal-epithelial interaction in prostate carcinoma and highlights the importance of GALNT14.

Gal-3 plays an important role in cell survival, mRNA splicing, and cell–cell and cell–matrix interactions. Depending on its cellular localization and cancer type, Gal-3 may have tumour-suppressive or tumour-promoting activities. Given the promising diagnostic role of Gal-3 in the urine of PCa patients found in our previous study, its concordant gene and protein expression levels, and its involvement in PCa-related biological processes (e.g., morphogenesis of the prostate gland epithelium), we aimed to investigate this protein immunohistochemically in tumour and normal prostate tissues. Gal-3 protein expression was evaluated in 48 tumour prostate tissues, eight normal prostate tissues and 14 adjacent-normal prostate tissues. Decreased Gal-3 staining was detected in tumour tissues compared with normal tissues. Although Gal-3 staining was decreased in tumour tissues with GS 5-8 and pT2 and pT3 stages compared with normal prostate tissue, no correlation was found between Gal-3 expression and PCa progression. In the present study, the pattern of cellular localization differed between groups, as Gal-3 was predominantly excluded from the nucleus in tumour tissues. Furthermore, Gal-3 had no significant effect on survival and relapse in these PCa patients. This work confirms Gal-3 as a promising marker for PCa diagnosis. [ABSTRACT FROM AUTHOR]

BackgroundProspective cohort studies of circulating sex steroid hormones and prostate cancer risk have not provided a consistent association, despite evidence from animal and clinical studies. However, studies using male pattern baldness as a proxy of early-life or cumulative androgen exposure have reported significant associations with aggressive and fatal prostate cancer risk. Given that androgens underlie the development of patterned hair loss and chest hair, we assessed whether these two dermatological characteristics were associated with circulating and intraprostatic concentrations of sex steroid hormones among men diagnosed with localized prostate cancer.MethodsWe included 248 prostate cancer patients from the NCI Prostate Tissue Study, who answered surveys and provided a pre-treatment blood sample as well as fresh frozen adjacent normal prostate tissue. Male pattern baldness and chest hair density were assessed by trained nurses before surgery. General linear models estimated geometric means and 95% confidence intervals (95%CIs) of each hormone variable by dermatological phenotype with adjustment for potential confounding variables. Subgroup analyses were performed by Gleason score (

Prostate cancer abnormality (PCA) is considered as one of the most prevalent cancer in which its clinical characteristics differ from low to aggressive stage. Lower-grade tumors do not develop to critical, whereas higher-grade tumors are invasive and they might develop into metastatic disease. There are several methods to detect prostate tissue abnormalities such as by utilizing AI (artificial intelligence); however, there exist certain limitations like security issues and computational complexity. To the best of our knowledge, this is the first work to identify the abnormalities in the prostate tissues by using two-dimensional photonic crystal tactile sensor. This study followed two sensing principles, such that the first principle deals with identifying the values of stress and force by displacement sensing principles. In addition, the second principle deals with finding displacement values by photonic crystal sensing principles. Moreover, the simulation tool used in this study is RSoft CAD software. The study calculated the values of stress, strain, and displacement and found that the stress value was significantly higher in cancer tissues than in normal tissues. Likewise, the force and displacement values were also found to be higher in cancer tissues. However, the stress, force, and displacement values were very less in benign prostatic hyperplasia (BPH) tissues. By utilizing the proposed photonic crystal tactile sensor, higher values of elastic modulus, stress, force, and displacement shows there is a higher possibility of cancer occurrence in the prostate tissues. In addition, the study finally indicated that the proposed system has obtained higher sensitivity values when compared to other displacement sensors. [ABSTRACT FROM AUTHOR]

Background: Early detection of prostate cancer has significant benefits for its treatment and can increase the survival chance in patients. In recent years, new methods such as shear wave elastography and vibro-elastography, as well as artificial tactile sensing, have been used to detect a mass in the prostate tissue in-vivo and ex-vivo. This paper aims to investigate the difference between normal and malignant prostate tissue reaction to simple and vibro-neural stimulation for prostate tissue mass detection in order to determine neural stimulation intensity, velocity, and frequency to obtain the best result in detecting the type and location of the tumor. Methods: This study has utilized neural stimulation devices in normal and cancerous tissues. The stimulation velocity, probe location, and the frequency of neural stimulation considered as the independent variables. Results: The results show that for superficial masses, although dependent on the probe, the accuracy of detection at the low speed of 5mm/s is 50% higher than other conditions. On the other hand, in deep masses, with increasing mass depth, the accuracy of detection at the medium speed of 8mm/s is 30% higher than the low speed. Finally, the results showed that with increased stimulation frequency, the possibility of tumor detection, and its accuracy increases by 35%. Conclusion: By improving the accuracy of the neural stimulation device, it can apply to detect hard materials such as tumors and malignant tissues.

Purpose: To determine the histological validity of the tissue acquired during aquablation of the prostate. Patients and methods: Prostatic tissue of 12 patients that consecutively underwent aquablation for benign prostatic enlargement was systematically examined. Histological examination was performed by two experienced uropathologists using a digital slide scanner and slide viewer software (Pannoramic 250 and Case Viewer 2.3, 3D Histech, Hungary). The surface areas of the assessable glands were examined and set in relation to the total surface area of the material available for histology and to the patient's total prostate volume. Examinations were performed analogously in ten consecutive patients undergoing transurethral resection of the prostate (TURP) to facilitate interpretation of the results. Data were analyzed using descriptive statistics. Results: A median of 4.06% (range 1.43–7.5%) of the preoperative total prostate volume (median 64.5 ml (range 40–80 ml)) was obtained for histological examination by aquablation. Due to severe mechanical destruction and fragmentation, only a proportion of 0.43% (0.06–1.79%) of this tissue represented histologically assessable glands. Therefore, roughly 0.017% of the total prostatic volume was available for a reliable histological examination. In comparison, 32.5% (6.67–37.5%) of the total prostate volume was removed by TURP and 22.86% (7.45–40.57%) of this tissue represented informative prostatic glands, corresponding to 7.43% of the total prostate volume. Conclusion: Histological significance of the tissue obtained by aquablation of the prostate is very limited. Costs and effort of the histological examination must, therefore, be weighed critically against the limited informative value. [ABSTRACT FROM AUTHOR]

• The polarization properties of malignant and benign bulk prostate tissues have been investigated. • MMPD, MMT and FDHs parameters quantitatively discriminate between healthy and cancerous. • Retardance and parameter A are the most significant parameter for discrimination. The polarimetry imaging technique has provided a powerful tool for discriminating normal from cancerous tissues. In this paper, based on the backscattering Mueller matrix imaging of prostate bulk tissues, (received immediately after surgery without any further processing), we have extracted the characteristic features of the Mueller matrix images. In order to provide a quantitative and more accurate comparison, three different methods have been used; the Mueller matrix polar decomposition (MMPD), the Mueller matrix transformation (MMT) and the frequency distribution histograms (FDHs) and their central moment parameters. Comparing different tissues, the results of our study indicate that these methods provide the indicators for the characteristics of the microstructural features of the tissues. The indicators have the potential to distinguish between cancerous and healthy tissues. Determining the polarimetric characteristics of the tissue immediately after surgery and prior to the pathology, and the potential possibility of this technique to be used in vivo as an optical biopsy technique, can significantly reduce the cost and time of diagnosis of cancer. [ABSTRACT FROM AUTHOR]

Background: In most cases, prostatitis can be caused by a bacterial agent such as Ureaplasma urealyticum. Considering to the cumbersome of the culture method for the detection of Ureaplasma species in clinical samples such as prostate; PCR method that is faster and more appropriate than the cultivation methods, can be utilized for the detection of U. urealyticum and U. parvum. PCR-RFLP method can differentiate both biovars and assist in studies of the clinical diagnosis, epidemiology and pathology of this species in human. The aim of this study was to molecular detection of U. urealyticumin in prostate tissue samples based on PCR- RFLP. Methods:Two hundred prostate tissue samples were collected from patient suffering from prostatitis. The PCR assay was used to amplify a 559 bp fragment of 16S-23SRNA interspace region of Ureaplasma. After sequencing, PCR products from positive samples were digested with TaqI restriction enzyme. Results: Seven cases (3.5%) out of 200 prostate tissue samples were positive for U. urealyticum. Results of PCR products sequencing demonstrated that all isolates were U. parvum biovar. PCR-RFLP results shown that there was not any differentiation in pattern of enzymatic digestion, in addition, all isolates were U. parvum, serovar 3. Conclusion: U. urealyticum can be one of the causing agents of prostatitis. Using PCR-RFLP with specific primer and restriction enzyme is a rapid and cost-effect method for detection and differentiation of Ureaplasma from clinical samples.

Fluoroquinolones are the drugs of choice in the prevention of bacterial infections after transrectal ultrasound guided prostate biopsy. In order to improve assessment of antibacterial efficacy in the target tissue a simple, selective, rapid and robust HPLC-ESI–MS/MS method for the determination of levofloxacin and ciprofloxacin concentrations in human prostate bioptates was developed and validated. Preparation procedure for prostate samples (10 mg) was carried out using homogenization and filtration steps. Analyses were performed within 3.5 min using RP C 18 column in the isocratic elution mode with mobile phase composed of a mixture of 0.1% formic acid aqueous solution and 0.1% formic acid methanol solution ( v/v ; 79:21). The method was linear between 0.3 μg/g and 15 μg/g for levofloxacin and ciprofloxacin with coefficient of correlation (r) ≥0.999. The limit of detection and the limit of quantification for levofloxacin were 0.06 μg/g and 0.2 μg/g and for ciprofloxacin were 0.04 μg/g and 0.13 μg/g, respectively. Average concentrations (±SD) of levofloxacin and ciprofloxacin obtained from patients tissue were 5.4 ± 2.2 μg/g and 3.9 ± 1.5 μg/g, respectively. Additionally, during validation procedure a novel, experimental design approach was applied for the robustness study. For evaluation of analytical method robustness, Plackett-Burman design was employed and for sample preparation method robustness Fractional Factorial design was used. The developed and validated method was successfully applied to examine prostate tissue samples obtained from patients enrolled into a clinical study. Up to now, there has been no other HPLC-ESI-MS/MS method reported for the simultaneous determination of levofloxacin and ciprofloxacin in human prostatic tissue. [ABSTRACT FROM AUTHOR]

Background: Despite a worldwide common and progressive nature of benign prostate hyperplasia (BPH) in older men, no association has been observed between a causative pathogen and other etiology so far. Methods: In this study, we investigated a causative association of Trichomonas vaginalis, a flagellate protozoan parasite, in 171 BPH cases presenting without symptoms of prostatitis at a surgical outpatient clinic in Kuwait. We detected T. vaginalis DNA by polymerase chain reaction (PCR) and T. vaginalis antigen by immunocytochemistry (ICC) in the prostate tissue of these cases. A total of 171 age-matched controls with no urinary tract symptoms were also included in the study. A detailed information regarding the sexual history and sexually transmitted infections (STIs) was enquired from all the enrolled subjects. Results: We detected T. vaginalis DNA and T. vaginalis antigen in 42 (24.6 %) and 37 (21.6 %) of the 171 BPH cases respectively in their prostate tissue. Both these assays showed a very good agreement and statistically no significant difference in their sensitivities and specificities. A relatively higher seropositivity rate for antibodies to T. vaginalis was detected in BPH cases (53 of 171 cases, 31.0 %) than in the control group (26.9 %) [p: 0.19] and both were higher than in earlier reports but no significant association was observed between BPH and T. vaginalis serostatus. However, a greater proportion of seroreactive BPH cases had high IgG2 antibody absorbance score than in the control group (p:0.000). Furthermore, no significant association was observed between T. vaginalis seropositivity and presence of T. vaginalis DNA in the prostate tissue. Conclusions: Our study documents T. vaginalis DNA and T. vaginalis antigen in 24.6 and 21.6 % respectively in the prostate tissue of the BPH cases. We also detected a relatively higher seropositivity rate for antibodies to T. vaginalis both in the BPH cases and in normal control group, 31 and 26.9 % respectively but no significant association was observed between BPH and T. vaginalis serostatus or presence of T. vaginalis DNA in the prostate tissue. Further epidemiological and case-controlled studies are needed to focus on local response to chronic asymptomatic retention of T. vaginalis in prostate tissue in the development of benign prostate hyperplasia. [ABSTRACT FROM AUTHOR]

This paper presents a retrospective study from 2004 to 2014 of FTIR prostate cancer spectroscopy related to tissues and cell biology. Since vibrational spectroscopy is delicately sensitive to the biochemical composition of the sample and variations therein, it is possible to monitor metabolic processes in tissue and cells, and to construct spectral maps based on thousands of collected IR spectra. These reveal information on tissue structure, distribution of cellular components, metabolic activity and the health condition of cells and tissues. In addition, rapid collection, reliable data, a powerful ability to structure elucidation about IR spectroscopy, and the need for a rapid diagnosis of traditional biopsy (subject to sampling and inter-observer) have potentiated infrared as a way for a new type of analysis based on optical examination and being more objective than conventional colour methods. [ABSTRACT FROM AUTHOR]

Fluoroquinolones are considered as gold standard for the prevention of bacterial infections after transrectal ultrasound guided prostate biopsy. However, recent studies reported that fluoroquinolone- resistant bacterial strains are responsible for gradually increasing number of infections after transrectal prostate biopsy. In daily clinical practice, antibacterial efficacy is evaluated only in vitro , by measuring the reaction of bacteria with an antimicrobial agent in culture media ( i.e . calculation of minimal inhibitory concentration). Such approach, however, has no relation to the treated tissue characteristics and might be highly misleading. Thus, the objective of this study was to develop, with the use of Design of Experiments approach, a reliable, specific and sensitive ultra-high performance liquid chromatography- diode array detection method for the quantitative analysis of levofloxacin in plasma and prostate tissue samples obtained from patients undergoing prostate biopsy. Moreover, correlation study between concentrations observed in plasma samples vs prostatic tissue samples was performed, resulting in better understanding, evaluation and optimization of the fluoroquinolone-based antimicrobial prophylaxis during transrectal ultrasound guided prostate biopsy. Box-Behnken design was employed to optimize chromatographic conditions of the isocratic elution program in order to obtain desirable retention time, peak symmetry and resolution of levofloxacine and ciprofloxacine (internal standard) peaks. Fractional Factorial design 2 4−1 with four center points was used for screening of significant factors affecting levofloxacin extraction from the prostatic tissue. Due to the limited number of tissue samples the prostatic sample preparation procedure was further optimized using Central Composite design. Design of Experiments approach was also utilized for evaluation of parameter robustness. The method was found linear over the range of 0.030–10 μg/mL for human plasma and 0.300–30 μg/g for human prostate tissue samples. The intra-day and inter-day variability for levofloxacine from both plasma and prostate samples were less than 10%, with accuracies between 93 and 108% of the nominal values. The limit of detection and the limit of quantification for human plasma were 0.01 μg/mL and 0.03 μg/mL, respectively. For the prostate tissue, the limit of detection and the limit of quantification were 0.1 μg/g and 0.3 μg/g, respectively. The average recoveries of levofloxacin were in the range from 99 to 106%. Also, the method fulfills requirements of robustness what was determined and proved by Design of Experiments. The developed method was successfully applied to examine prostate tissue and plasma samples from 140 hospitalized patients enrolled into the clinical study, 12 h after oral administration of LVF at a dose of 500 mg. The mean (± SD) LVF concentration in prostate was 6.22 ± 3.52 μg/g and in plasma 2.54 ± 1.14 μg/mL. Due to simplicity of the method and relative small amount of sample needed for the assay, the method can be applied in clinical practice for monitoring of LVF concentrations in plasma and prostate gland. [ABSTRACT FROM AUTHOR]

Background: In most cases, prostatitis can be caused by a bacterial agent such as Ureaplasma urealyticum. Considering to the cumbersome of the culture method for the detection of Ureaplasma species in clinical samples such as prostate; PCR method that is faster and more appropriate than the cultivation methods, can be utilized for the detection of U. urealyticum and U. parvum. PCR-RFLP method can differentiate both biovars and assist in studies of the clinical diagnosis, epidemiology and pathology of this species in human. The aim of this study was to molecular detection of U. urealyticumin in prostate tissue samples based on PCR- RFLP. Methods: Two hundred prostate tissue samples were collected from patient suffering from prostatitis. The PCR assay was used to amplify a 559 bp fragment of 16S-23SRNA interspace region of Ureaplasma. After sequencing, PCR products from positive samples were digested with TaqI restriction enzyme. Results: Seven cases (3.5%) out of 200 prostate tissue samples were positive for U. urealyticum. Results of PCR products sequencing demonstrated that all isolates were U. parvum biovar. PCR-RFLP results shown that there was not any differentiation in pattern of enzymatic digestion, in addition, all isolates were U. parvum, serovar 3. Conclusion: U. urealyticum can be one of the causing agents of prostatitis. Using PCR-RFLP with specific primer and restriction enzyme is a rapid and cost-effect method for detection and differentiation of Ureaplasma from clinical samples. [ABSTRACT FROM AUTHOR]

Abstract: An X-ray transmission microtomography (CT) system combined with an X-ray fluorescence microtomography (XRFμCT) system was implemented in the Brazilian Synchrotron Light Laboratory (LNLS), in order to determine the elemental distribution in prostate samples aiming at establishing a correlation between the concentration of some elements and the characteristics and pathology of the tissues. The CT images were reconstructed using a filtered-back projection algorithm and the XRFμCT images were reconstructed using a filtered-back projection algorithm with absorption corrections. [Copyright &y& Elsevier]

AIM The aim of this small patient study was to investigate tamsulosin concentrations in prostate and plasma samples in order to identify potential differences in the pharmacokinetics (PK) in plasma and prostate contributing to its pharmacodynamic activity profile in patients. METHODS Forty-one patients with benign prostatic hyperplasia (BPH) scheduled for open prostatectomy were given tamsulosin 0.4 mg for 6-21 days in order to reach steady-state PK. Patients were randomized over four groups to allow collection of plasma and tissue samples at different time points after last dose administration. Samples were collected during surgery and assayed for tamsulosin HCl. The free fraction (fu) of tamsulosin was determined by ultracentrifugation of plasma and prostate tissue spiked with 14C-tamsulosin. RESULTS Cmax in plasma at 4.4 h for total tamsulosin was 15.2 ng ml-1 and AUC(0,24 h) was 282 ng ml-1 h, while for prostate Cmax at 11.4 h post-dose was 5.4 ng ml-1 and AUC(0,24 h) was 120 ng ml-1 h. AUC(0,24 h) for total tamsulosin in prostate was 43% of the plasma AUC(0,24 h). fu was 0.4 % for plasma and 59.1% for prostate. Therefore calculated on unbound tamsulosin, a ratio of 63 resulted for prostate vs. plasma Cmax concentrations. CONCLUSIONS These data indicate that in patients with confirmed BPH the amount of tamsulosin freely available in the target tissue (prostate) is much higher than in plasma. [ABSTRACT FROM AUTHOR]

Abstract: Certain pesticides are able to disturb the sex steroid hormone system and to act as antiandrogens. While the different underlying mechanisms remain unclear, inhibition of 5α-reductase, the enzyme which is indispensable for the synthesis of DHT and thus normal masculinization, appears to be one of the sensitive targets for endocrine disruption. We therefore tested several endocrine disrupters with antiandrogenic effects in vivo for their influence on 5α-reductase activity in two different test systems: (a) an enzyme assay with human Lymph Node Carcinoma of Prostate (LNCaP) cells and (b) an enzyme assay with human prostate tissue homogenate. The selected pesticides and industrial compounds were monobutyltin (MBT), dibutyltin (DBT), tributyltin (TBT), triphenyltin (TPT), diuron, fenarimol, linuron, p,p′DDE, prochloraz and vinclozolin. The synthetic androgen methyltestosterone and the synthetic antiandrogen flutamide, as well as the 5α-reductase inhibitor finasteride served as control compounds. The effect of the organotin compounds DBT, TBT and TPT on enzyme activity was approximately the same in both test systems, with IC50 values ranging between 2.7 and 11.2μM, while in prostate tissue, methyltestosterone and prochloraz proved to be stronger inhibitors (IC50 values of 1.9 and 12.4μM) than in LNCaP cells (IC50 values of 13.2 and 53.2μM). The inhibitory impact of finasteride was approximately 130 times stronger in prostate tissue than in LNCaP cells. Fenarimol, flutamide, linuron and p,p′DDE inhibited 5α-reductase activity only at very high concentrations (IC50 ⩾24μM) in prostate homogenates, and not at all in LNCaP cells. On average, the IC20 values were 3.5 times lower than the IC50 values. Diuron, MBT and vinclozolin exerted no effect in either of the test systems. The finding of pesticides acting as 5α-reductase inhibitors might be of clinical relevance. As a screening tool for putative ED, the tissue assay is the more practical and sensitive method. However, the cell assay can, to some extent, reflect particular cell processes since the living cell is able to compensate moderate toxicological effects of the ED on cell viability, and possibly also their impact on 5α-reductase activity. [Copyright &y& Elsevier]

Prostate cancer is the most common form of cancer in men in Europe and in the USA. Some prostate tumours are stiffer than the surrounding normal tissue, and it could therefore be of interest to measure prostate tissue stiffness. Resonance sensor technology based on piezoelectric resonance detects variations in tissue stiffness due to a change in the resonance frequency. An impression-controlled resonance sensor system was used to detect stiffness in silicone rubber and in human prostate tissue in vitro using two parameters, both combinations of frequency change and force. Variations in silicone rubber stiffness due to the mixing ratio of the two components could be detected (p<0.05) using both parameters. Measurements on prostate tissue showed that there existed a statistically significant (MANOVA test, p<0.001) reproducible difference between tumour tissue (n=13) and normal healthy tissue (n=98) when studying a multivariate parameter set. Both the tumour tissue and normal tissue groups had variations within them, which were assumed to be related to differences in tissue composition. Other sources of error could be uneven surfaces and different levels of dehydration for the prostates. Our results indicated that the resonance sensor could be used to detect stiffness variations in silicone and in human prostate tissue in vitro. This is promising for the development of a future diagnostic tool for prostate cancer. [ABSTRACT FROM AUTHOR]

The recent development of Fourier transform infrared (FTIR) spectroscopic imaging has enhanced our capability to examine, on a microscopic scale, the spatial distribution of vibrational spectroscopic signatures of materials spanning the physical and biomedical disciplines. Recent activity in this emerging area has concentrated on instrumentation development, theoretical analyses to provide guidelines for imaging practice, novel data processing algorithms, and the introduction of the technique to new fields. To illustrate the impact and promise of this spectroscopic imaging methodology, we present fundamental principles of the technique in the context of FTIR spectroscopy and review new applications in various venues ranging from the physical chemistry of macromolecular systems to the detection of human disease. [ABSTRACT FROM AUTHOR]

Background: Dietary fatty acids may influence prostate carcinogenesis. Although the standard for assessing dietary effects in humans is the semiquantitative food-frequency questionnaire, the extent to which self-reported intake correctly ranks prostatic exposure is unknown. Objective: The objective was to examine the correlation between reported intakes of different fatty acids and their concentrations in prostate tissue. Design: This was a cross-sectional study of 52 men undergoing surgical resection of the prostate gland. Usual dietary intake of saturated, total unsaturated, oleic, and linoleic fatty acids over the previous year was estimated with use of a 122-item version of the Health Habits and History Questionnaire. Concentrations in prostate tissue were measured directly by use of gas chromatography in healthy tissue collected at the time of surgery and were expressed as a percentage of total fatty acids. Correlations with 4 measures of dietary intake [g/d, g/d adjusted for total daily energy intake, % of total fat (as g/d), and % of total energy] were evaluated by Spearman's rank-order correlation coefficients. Results: Linoleic acid concentrations in prostate tissue were significantly correlated with dietary intake expressed as g/d adjusted for total energy [r = 0.29 (95% CI: 0.03, 0.49), P = 0.04], % of total fat [r = 0.36 (0.14, 0.550), P = 0.008], and % of total energy [r = 0.28 (0.04, 0.49), P = 0.042], but not as g/d. Although mean concentrations of saturated, total unsaturated, and oleic fatty acids in prostate tissue resembled mean intakes for the group, prostatic concentrations did not correlate with individual intakes. Conclusion: Self-reported intake of fatty acids is a satisfactory marker of prostatic exposure at the group level, but, with the exception of linoleic acid, does not correctly rank individuals with respect to intensity of exposure. [ABSTRACT FROM AUTHOR]

MALDI MS imaging (MSI) is a powerful analytical tool for spatial peptide detection in heterogeneous tissues. Proper sample preparation is crucial to achieve high quality, reproducible measurements. Here we developed an optimized protocol for spatially resolved proteolytic peptide detection with MALDI time-of-flight MSI of fresh frozen prostate tissue sections. The parameters tested included four different tissue washes, four methods of protein denaturation, four methods of trypsin digestion (different trypsin densities, sprayers, and incubation times), and five matrix deposition methods (different sprayers, settings, and matrix concentrations). Evaluation criteria were the number of detected and excluded peaks, percentage of high mass peaks, signal-to-noise ratio, spatial localization, and average intensities of identified peptides, all of which were integrated into a weighted quality evaluation scoring system. Based on these scores, the optimized protocol included an ice-cold EtOH+H 2 O wash, a 5 min heating step at 95°C, tryptic digestion incubated for 17h at 37°C and CHCA matrix deposited at a final amount of 1.8 μg/mm 2 . Including a heat-induced protein denaturation step after tissue wash is a new methodological approach that could be useful also for other tissue types. This optimized protocol for spatial peptide detection using MALDI MSI facilitates future biomarker discovery in prostate cancer and may be useful in studies of other tissue types., (© 2022 The Authors. Proteomics published by Wiley-VCH GmbH.)

Tumor cells cultured in a physiologically related three-dimensional (3D) matrix can replicate many basic characteristics of tumor tissue. Tumor tissues are harder than normal, so when using hydrogels for 3D tumor cell culture, attempts have been made to prepare hydrogel scaffolds that mimic the hardness of tumor tissues without reducing the porosity. In this study, a new 3D loofah-inspired scaffold was developed for prostate cancer cell culture. Since the loofah sponge structure of the spacer fabric, the composite scaffolds had a compression modulus similar to that of natural prostate tumor tissue at a lower hydrogel concentration (0.25% W/V), and also, endowed the scaffold with high porosity (85 ± 2.52%) for mass transfer. The results of in vitro cell experiments showed that the composite scaffold can support tumor cells to form clusters in a short time (3 days). Preliminary chemosensitivity analysis showed that the drug resistance of the composite scaffold was significantly higher than that of two-dimensional (2D) culture and COL scaffold. Therefore, the 3D tumor cell culture scaffold with bionic structures has the potential to be used as a tumor drug screening model., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Simple Summary: Prostate cancer (PCa) is one of the leading cancer deaths in man's world. Due to the lack of a fast and sensitive diagnostic method, PCa is only recognized in the late stadium of the disease. For this purpose, new tools are sought for sensitive diagnosis. One of them is the use of mass spectrometry. The main goal of the study was to perform target lipidomic analysis of prostate tissue with the use of two imaging methods: matrix-assisted laser desorption ionization with time-of-flight mass spectrometer, and electrospray ionization with triple quadrupole mass spectrometer. Statistical evaluation provided the knowledge about the phospholipids alteration linked with PCa progression. In practice, its recognition enables development of a quick and sensitive diagnostic method. The acquired knowledge may also lead to the increasement of hormone therapies effectiveness. The main goal of this study was to explore the phospholipid alterations associated with the development of prostate cancer (PCa) using two imaging methods: matrix-assisted laser desorption ionization with time-of-flight mass spectrometer (MALDI-TOF/MS), and electrospray ionization with triple quadrupole mass spectrometer (ESI-QqQ/MS). For this purpose, samples of PCa tissue (n = 40) were evaluated in comparison to the controls (n = 40). As a result, few classes of compounds, namely phosphatidylcholines (PCs), lysophosphatidylcholines (LPCs), sphingomyelins (SMs), and phosphatidylethanolamines (PEs), were determined. The obtained results were evaluated by univariate (Mann–Whitney U-test) and multivariate statistical analysis (principal component analysis, correlation analysis, volcano plot, artificial neural network, and random forest algorithm), in order to select the most discriminative features and to search for the relationships between the responses of these groups of substances, also in terms of the used analytical technique. Based on previous literature and our results, it can be assumed that PCa is linked with both the synthesis of fatty acids and lipid oxidation. Among the compounds, phospholipids, namely PC 16:0/16:1, PC 16:0/18:2, PC 18:0/22:5, PC 18:1/18:2, PC 18:1/20:0, PC 18:1/20:4, and SM d18:1/24:0, were assigned as metabolites with the best discriminative power for the tested groups. Based on the results, lipidomics can be found as alternative diagnostic tool for CaP diagnosis. [ABSTRACT FROM AUTHOR]