Prostate Morphology Research Articles

High-fat diet impact on prostate gland from adiponectin knockout mice: Morphometric, metabolic and inflammatory cytokines analyses

AimsObesity is a global public health issue, and some studies have linked it to an increased risk of prostatic diseases. This study aimed to evaluate the effects of a high-fat diet on metabolic parameters and prostate morphology in wild-type (WT) and adiponectin knockout (KO) mice. Main methodsMale WT and KO mice were fed a control diet (CD) or high-fat diet (HFD) for 6 months. Serum metabolic parameters, inflammatory cytokines in epididymal fat tissue, dorsal prostatic lobe morphometry and histopathology were analyzed. Key findingsCD WT and CD KO mice did not exhibit altered metabolic or prostatic parameters. However, HFD WT mice showed altered glucose and insulin tolerance even without excessive weight gain. On the other hand, HFD KO mice developed obesity, with an increase in low-density lipoprotein (11.8 ± 5.1 vs. 31.4 ± 3.6 mg/dL), high-density lipoprotein (73.4 ± 7.4 vs. 103.4 ± 2.5 mg/dL), and total cholesterol levels (126.2 ± 16.1 vs. 294.6 ± 23.2 mg/dL), a decrease in insulin levels (28.7 ± 12.2 vs. 4.6 ± 2.3 μIU/mL), and glucose and insulin resistance. We also observed that HFD KO animals display an increase in inflammatory cytokines, such as IL6, IL1β, and IL1RA. The dorsal prostate from HFD KO animals also presented significant increases in the mast cells (1.9 ± 0,7 vs. 5,3 ± 1.5 cells/field) and Ki67 index (2.91 ± 0.6 vs. 4.7 ± 0.4 %). SignificanceThe above findings highlight the complex interactions between adiponectin, metabolism, malnutrition, and prostate health. Metabolic deregulation combined with adipose inflammation potentially induces a proliferative and inflammatory microenvironment in the prostate gland under conditions of low adiponectin production, potentially impairing prostate morphophysiology in the context of obesity and aging.

PI-RADS v2.1 evaluation of prostate "nodule in nodule" variants: clinical, imaging, and pathological features.

To analyze the correlation among the imaging features of prostate "nodule in nodule," clinical prostate indices, and pathology results. We retrospectively analyzed the prostate images from 47 male patients who underwent MRI scans and pathological biopsy from January 2022 to July 2023. Two radiologists (R1/R2) evaluated the morphology and signal intensity of the "nodule in nodule" in a double-blind manner and calculated the PI-RADS v2.1 score, which was compared with clinical prostate indices and pathological results. 34.04% (16/47) of patients were pathologically diagnosed with clinically significant prostate cancer (csPCa). Total prostate-specific antigen (tPSA), free/t PSA, PSA density (PSAD), and prostate gland volume (PGV) were significantly different between csPCa patients and benign prostatic hyperplasia (BPH) patients with prostate "nodule in nodule". R1/R2 detected 17/17 prostate "nodule in nodule" pathologically confirmed as csPCa on MRI; 10.60% (16/151) (R1) and 11.11% (17/153) (R2) had diffusion-weighted imaging (DWI) PI-RADS v2.1 score of 4, and 0.66% (1/151) (R1) had a score of 3. The percentages of encapsulated, circumscribed, and atypical nodules and obscured margins were 0.00% (0/151), 0.00% (0/151), 5.96% (9/151), and 5.30% (8/151), respectively, for R1, and 0.00% (0/153), 0.00% (0/153), 5.88% (9/153), and 4.58% (7/153) for R2. When the inner nodules of "nodule in nodule" lesions in PI-RADS v2.1 category 1 in the TZ show incomplete capsulation or obscured margins, they are considered atypical nodules and might be upgraded to PI-RADS v2.1 category 3 if they exhibit marked diffusion restriction. However, further validation is needed. This study first analyzed the relationship between clinical and pathological findings and the size, margin, and multimodal MRI manifestations of the prostate "nodule in nodule." These findings could improve the diagnostic accuracy of PI-RADS v2.1 for prostate lesions. • The margin of the prostate inner nodules affects the PI-RADS v2.1 score. • The morphology of prostate "nodule in nodule" is related to their pathology. • The PI-RADS v2.1 principle requires consideration of prostate "nodule in nodule" variants.

Digital postprocessing analysis of prostatic perfusion in neutered dogs.

B-mode ultrasound is routinely performed to evaluate the prostate gland in neutered dogs, although, the detection of malignancies may be challenging. Contrast-enhanced ultrasound (CEUS) has shown to be useful for the assessment of prostatic perfusion in normal and diseased dogs, although the interpretation of contrast ultrasonographic features may still be subjective. A quantitative tool for evaluating prostatic perfusion might improve the reliability of the results in terms of early detection of prostate neoplasia in neutered dogs. The present study aimed to evaluate the applicability of a postprocessing analysis tool to CEUS of the prostate in healthy neutered dogs, to provide quantitative measurements, and to study the influence of individual characteristics on prostatic regression. Twenty-three neutered dogs underwent a B-mode and CEUS examination of the prostate to acquire data about prostatic morphology and microcirculation. The prostate was imaged using a 5-7.5MHz linear transducer and contrast was administered intravenously. Videoclips were analyzed by using Qontrast software and a postprocessing digital analysis tool (ImageJ) to measure perfusion peak intensity, time to peak, and vascularization ratio at the moment of the peak, which were then related to body weight, age, and time elapsed since orchiectomy. Correlation tests revealed higher vascularization in younger compared with older dogs (P<.05) and in smaller compared with larger dogs (P<.05). Time elapsed since orchiectomy (P>.05) did not affect prostatic perfusion. Contrast-enhanced ultrasound and the postprocessing analysis tool ImageJ allowed analysis of vascular perfusion in all dogs and have the potential to improve the diagnostic possibilities for andrological examination.

Prostatic morphological changes throughout life: Cytochemistry as a tool to reveal tissue aging markers.

The prostate undergoes normal or pathological morphological changes throughout life. An understanding of these changes is fundamental for the comprehension of aging-related pathological processes such as benign prostatic hyperplasia (BPH) and cancer. In the present study, we show some of these morphological changes, as well as histochemical techniques like Weigert's resorcin-fuchsin method, Picrosirius Red, and Gömöri's reticulin for use as tools in the study of prostate tissue under light microscopy. For this purpose, prostates of the Mongolian gerbil (n = 9), an experimental model that develops BPH spontaneously, were analyzed at three life stages: young (1 month old), adult (3 months old), and old (15 months old). The results showed that fibrillar components such as collagen, and reticular and elastic fibers, change throughout life. In young animals, the prostate has cuboidal epithelium surrounded by thin layers of smooth muscle, continuous collagen fibers, winding reticular fibers, and sporadic elastic fibers. With adulthood, the epithelium becomes columnar, encircled by compacted muscle cells among slender collagen fibers, elongated reticular fibers, and linear elastic fibers. In aging individuals, the prostate's epithelium stratifies, surrounded by thick muscle layers among dense collagen fibers, disordered reticular fibers, and elastic fibers in different planes. We also identified a few accumulations of lipid droplets and lipofuscin granules in adult animals and high accumulation in old animals evidenced by Oil red O and Gömöri-Halmi techniques, respectively. The histochemical techniques presented here have been demonstrated to be useful and accessible tools in prostate studies. RESEARCH HIGHLIGHTS: Cytochemical techniques to study prostate morphology. The prostate changes with age.

Effectiveness of selenium in maintaining morphological architecture of prostatic compartments in mongolian gerbil

Male prostate is a reproductive gland that is under steroid hormones influence, which is object of several studies related to proliferative lesions that may arise during the aging process. Selenium is a micro-nutrient that has been described as a toxic mineral if administered at high concentrations but can also be beneficial mineral exerting a protective action on various tissues used properly. This mineral can be found in some foods such as Brazil nuts, grains, cereals and some vegetables. Mongolian gerbil prostate have morphophysiological similarities between the human prostate and has been used for comparative studies. This work aims to analyze the morphology and stereology of Mongolian gerbil prostate after selenium supplementation, followed by testosterone injection. Animals were divided into 3 groups (5 per group): GC intact animals; TG testosterone injection (1 mg/kg) for 21 days; TSG, selenium administration and testosterone injection (1 mg/kg) for 21 days. After experimental phase, animals were euthanized and prostate was dissected, fixed in metacarn, embedded, and sections were stained with hematoxylin-eosin (HE) for morphological and morphometric/stereological analyses. Analyzes showed that prostate epithelium of TG showed points of stratification and higher columnar cells when compared to CG and TSG. Already stereological analysis showed that the volume of epithelium in TG and TSG was higher than in CG. Besides, non-muscular volume of TG stroma showed higher than in TSG and CG. In conclusion, selenium is, in this concentration, an important factor that acts in maintenance of prostate morphology, even under the influence of exogenous testosterone.

2,4-dichlorophenoxyacetic acid (2,4-D) exposure during postnatal development alters the effects of western diet on mouse prostate

Western diet (WD), abundant in saturated fats and simple carbohydrates, has been associated with the development of prostate diseases. In addition, 2,4-dichlorophenoxyacetic acid (2,4-D), an herbicide used in agricultural and non-agricultural settings, may interfere with the endocrine system impacting reproductive health. The association of both factors is something common in everyday life, however, there are no relevant studies associating them as possible modulators of prostatic diseases. This study evaluated the action of the herbicide 2,4-D on the postnatal development of the prostate in mice fed with WD. Male C57Bl/6J mice received simultaneously a WD and 2,4-D at doses of 0.02, 2.0, or 20.0 mg/kg b.w./day for 6 months. The prolongated WD intake induced obesity and glucose intolerance, increasing body weight and fat. WD induced morphological changes and increased PCNA-positive epithelial cells in prostate. Additionally, the WD increased gene expression of AR, antioxidant targets, inflammation-related cytokines, cell repair and turnover, and targets related to methylation and miRNAs biosynthesis compared to the counterpart (basal diet). 2,4-D (0.02 and 2.0) changed prostate morphology and gene expression evoked by WD. In contrast, the WD group exposed to 20 mg/kg of 2,4-D reduced feed intake and body weight, and increased expression of androgen receptor and genes related to cell repair and DNA methylation compared to the negative control. Our results showed that 2,4-D was able to modulate the effects caused by WD, mainly at lower doses. However, further studies are needed to elucidate the mechanisms of 2,4-D on the obesogenic environment caused by the WD.

Polychlorinated Biphenyls (PCBs) Impact Prostatic Collagen Density and Bladder Volume in Young Adult Mice Exposed during in Utero and Lactational Development.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants linked to deleterious health outcomes, including voiding dysfunction in developmentally exposed mice. Changes in prostate volume and/or extracellular matrix composition are associated with voiding dysfunction in men and animal models. Whether PCB-induced changes in voiding function in male mice occur in part via alterations to the prostate or an alternate mechanism is unclear. Therefore, we tested whether developmental exposure to the MARBLES PCB mixture altered prostate morphology in young adult offspring. C57Bl/6J female mice were dosed daily with the MARBLES PCB mixture at 0, 0.1, 1 or 6 mg/kg/d for two weeks prior to mating and through gestation and lactation, offspring were collected at 6 weeks of age. Ventral prostate mass was decreased in the 1 mg/kg/d PCB group compared to other PCB groups. There were no PCB-induced changes in prostate smooth muscle thickness, apoptosis, proliferation, or testes mass. PCBs impacted the prostate extracellular matrix; anterior prostate collagen density was decreased in the 1 mg/kg/d PCB group compared to all other groups. Normalized bladder volume was increased in male and female offspring in the 6 mg/kg/d PCB group compared to control. No change in water consumption, bladder mass or bladder smooth muscle thickness accompanied changes in bladder volume. Urine and serum creatinine concentrations were elevated but only in male mice. Together, these results suggest that developmental exposure to PCBs can influence prostate wet weight and prostate/bladder morphology, but PCBs do not promote prostate enlargement. Whether these changes persist throughout adult life and how they contribute to voiding function in animal models and humans is of future interest.

Exposure to Dichlorvos pesticide alters the morphology of and lipid metabolism in the ventral prostate of rats.

Organophosphate pesticides are widely used in agriculture, leading to soil, water, and food contamination. Among these compounds is Dichlorvos [O,O-dimethyl O-(2,2-dichlorovinyl)phosphate, DDVP], which is listed as a highly toxic compound by the Environmental Protection Agency and World Health Organization. Exposure to DDVP can result in nervous, respiratory, hepatic, and reproductive abnormalities, in addition to endocrine disrupting, mutagenic, and carcinogenic effects. Little is known about the impacts of DDVP on the reprogramming of lipid metabolism, which is also associated with the development and progression of cancer, since the tumor cells need to recruit, capture, and use fatty acids to compose their building membranes. This study aimed to evaluate the influence of the pesticide DDVP on lipid metabolism in the prostate, after chemical induction by the carcinogen N-methyl-N-nitrosourea (MNU). For this, 32 Fischer rats aged 90days were randomly divided into four experimental groups: Control, DDVP, MNU, and MNU + DDVP. The MNU and MNU + DDVP groups underwent chemical induction with MNU (15mg/kg) and the DDVP and MNU + DDVP groups received a diet supplemented with DDVP (10mg/kg). Histopathological analyses of the rat ventral prostate showed 100% incidence of epithelial hyperplasia in the MNU and MNU + DDVP groups. This finding was accompanied by an increase of the epithelial compartment in the MNU + DDVP group. Immunolocalization of important proteins linked to lipid metabolism has been established. In the MNU + DDVP group, Western blotting analyses pointed out an increased expression of the protein LIMP II (Lysosomal Integral Membrane Protein-II), which is correlated with the capture and distribution of lipids in tumor cells. Together, these results indicate that the association of a low dose of DDVP with MNU was able to promote alterations in the morphology and lipid metabolism of the rat ventral prostate, which may be related to tumor progression in this organ.

The impacts of exposure to bisphenol A in the adult female prostate Meriones unguiculatus

The female prostate is associated with the urogenital system and presents homology in morphological terms with the male prostate. Due to its responsiveness to endogenous hormones, this gland is under a constant risk of developing prostatic pathologies and neoplasia when exposed to certain exogenous compounds. Bisphenol A (BPA) is an endocrine disruptor found in different plastic and resin products. Studies have emphasized the effects of perinatal exposure to this compound on different hormone-responsive organs. However, there have been few studies highlighting the influence on female prostate morphology of perinatal exposure to BPA. The objective of this study was to describe the histopathological alterations caused by perinatal exposure to BPA (50 µg/kg) and 17-β estradiol (E2) (35 µg/kg) in the prostate of adult female gerbils. The results showed that E2 and BPA induced proliferative lesions in the female prostate and acted along similar pathways by modulating steroid receptors in the epithelium. BPA was also found to be a pro-inflammatory and pro-angiogenic agent. The impacts of both agents were marked in the prostatic stroma. An increase in the thickness of the smooth muscle layer and a decrease in AR expression were observed, but no alterations in the expression of ERα and ERβ, leading to estrogenic sensitivity of the prostate. However, a peculiar response of the female prostate was to diminish the collagen frequency under BPA exposure correlated to smooth muscle layer. These data therefore indicate the development of features related to estrogenic and non-estrogenic tissue repercussions by BPA perinatally exposure in gerbil female prostate.

The prostatic middle lobe: clinical significance, presentation and management.

The role of the prostatic middle lobe in the presentation and management of benign prostatic hyperplasia (BPH) is under-appreciated. Middle lobe enlargement is associated with intravesical prostatic protrusion (IPP), which causes a unique type of bladder outlet obstruction (BOO) via a 'ball-valve' mechanism. IPP is a reliable predictor of BOO and the strongest independent factor for failure of medical therapy necessitating conversion to surgical intervention. Men with middle lobe enlargement tend to exhibit mixed symptoms of both the storage and the voiding types, but symptomatology will vary depending on the degree of IPP present. Initial assessments such as uroflowmetry and post-void residual volumes are inadequate to detect IPP and could confound the clinical picture. Radiological evaluation of prostate morphology is key to assessment as it provides important prognostic information and can help with operative planning. Treatment strategies employed for BPH should consider the shape and morphology of prostate adenomata, specifically the presence of middle lobe enlargement and the degree of associated IPP.

Development and clinical utility analysis of a prostate zonal segmentation model on T2-weighted imaging: a multicenter study

ObjectivesTo automatically segment prostate central gland (CG) and peripheral zone (PZ) on T2-weighted imaging using deep learning and assess the model’s clinical utility by comparing it with a radiologist annotation and analyzing relevant influencing factors, especially the prostate zonal volume.MethodsA 3D U-Net-based model was trained with 223 patients from one institution and tested using one internal testing group (n = 93) and two external testing datasets, including one public dataset (ETDpub, n = 141) and one private dataset from two centers (ETDpri, n = 59). The Dice similarity coefficients (DSCs), 95th Hausdorff distance (95HD), and average boundary distance (ABD) were calculated to evaluate the model’s performance and further compared with a junior radiologist’s performance in ETDpub. To investigate factors influencing the model performance, patients’ clinical characteristics, prostate morphology, and image parameters in ETDpri were collected and analyzed using beta regression.ResultsThe DSCs in the internal testing group, ETDpub, and ETDpri were 0.909, 0.889, and 0.869 for CG, and 0.844, 0.755, and 0.764 for PZ, respectively. The mean 95HD and ABD were less than 7.0 and 1.3 for both zones. The U-Net model outperformed the junior radiologist, having a higher DSC (0.769 vs. 0.706) and higher intraclass correlation coefficient for volume estimation in PZ (0.836 vs. 0.668). CG volume and Magnetic Resonance (MR) vendor were significant influencing factors for CG and PZ segmentation.ConclusionsThe 3D U-Net model showed good performance for CG and PZ auto-segmentation in all the testing groups and outperformed the junior radiologist for PZ segmentation. The model performance was susceptible to prostate morphology and MR scanner parameters.

Effect of electroacupuncture on the morphology of prostate and degranulation of mast cells in rats with chronic nonbacterial prostatitis

To observe the effect of electroacupuncture (EA) on the morphology of prostate and degranulation of mast cells in prostate of rats with chronic nonbacterial prostatitis (CNP). Male SD rats were randomly divided into sham operation group, model group and EA group, with 8 rats in each group. CNP model was established by surgical castration combined with 17-β estradiol injection once daily for 30 days. EA was applied to "Zhongji" (CV3), "Guanyuan" (CV4) and bilateral "Dahe" (KI12) for 20 min, once daily for 8 days. The mechanical pain threshold of scrotum skin area was tested before modeling, after modeling and after intervention. The pathological morphology of the prostate was observed by HE staining. Collagenous fiber was observed by Masson staining. The infiltration of mast cells was observed by toluidine blue staining. The contents of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in prostate were determined by ELISA. The protein expression levels of tryptase and transforming growth factor β1 (TGF-β1) in prostate were detected by Western blot. A normal appearance with little inflammatory cell infiltration was observed in the prostate of the sham operation group. Gland atrophy, epithelial destruction, hyperemia and edema, diffuse inflammatory cell infiltration and visible collagen fiber deposition were observed in prostate of the model group. The degree of infiltration of inflammatory cells and collagen fiber deposition were reduced in the EA group. Compared with the sham operation group, mechanical pain threshold was decreased (P<0.01), while the collagen volu-me fraction (CVF) of prostate, the degranulated rate of mast cells, the protein expression levels of tryptase and TGF-β1, and the contents of IL-6 and TNF-α were increased (P<0.01) in the model group. Following EA intervention, compared with the model group, the mechanical pain threshold was increased (P<0.01), CVF of the prostate, the degranulated rate of mast cells, the protein expression levels of tryptase and TGF-β1, and the contents of IL-6 and TNF-α were decreased (P<0.05, P<0.01) in the EA group. EA can relieve pain and reduce inflammation and fibrosis of prostate in CNP rats, which may be related to inhibiting the degranulation of prostate mast cells and down-regulating the expression of inflammatory factors and TGF-β1.

Effects of chronic restraint stress in the prostate of prepubertal and adult rats.

To investigate the effects of chronic stress in the prostate of prepubertal and adult rats. Thirty-two male rats were assigned into four groups depending on the type of treatment (control or stressed) and the age at which stress was initiated (prepubertal or adult). Restraint stress stimuli were applied for six weeks. Stressed prepubertal and adult rats evaluated immediately after the last stress stimuli were named SP and SA groups, respectively. Age-matched rats were used as control groups (CP and CA). At the end of the experiment, the rats were euthanized, and prostate morphological parameters were evaluated and statistically compared. Application of stress stimuli to the SP group resulted in reduced body weight, but no prostate morphological modification was noted. The SA group showed reduced testosterone level and prostatic epithelium surface density, in comparison to CA group. Further, the prostatic lumen surface density was increased in adult stressed animals, in comparison to adult controls. The stress stimuli promoted changes in hormonal and morphological parameters in the prostate of adult stressed rats. Prepubertal stressed animals did not presented modifications of prostate morphology.

Tempol differential effect on prostate cancer inflammation: In vitro and in vivo evaluation.

Tempol is a redox-cycling nitroxide that acts directly on inflammation. However, few studies have reported the use of tempol in prostate cancer (PCa). The present study investigated the effects of tempol on inflammation related to NF-κB signaling, using hormone-dependent or hormone-independent cell lines and the transgenic adenocarcinoma of the mouse prostate PCa animal model in the early and late stages of cancer progression. PC-3 and LnCaP cells were exposed to different tempol doses in vitro, and cell viability assays were performed. The optimal treatment dose was chosen for subsequent analysis using western blotting. Fiveexperimental groups were evaluated in vivo to test for tempol effects in the early (CT12 and TPL12 groups) and late stages (CT20, TPL20-I, and TLP20-II) of PCa development. The TPL groups were treated with 50 or 100 mg/kg tempol. All control groups received water as the vehicle. The ventral lobe of the prostate was collected and subjected to immunohistochemical and western blotanalysis. Tempol treatment reduced cellular proliferation in vitro and improved prostatic morphology in vivo, thereby decreasing tumor progression. Tempol reduced inflammation in preclinical models, and downregulated the initial inflammatory signaling through toll-like receptors, not always mediated by the MyD88 pathway. In addition, it upregulated iκB-α and iκB -β levels, leading to a decrease in NF-κB, TNF-α, and other inflammatory markers. Tempol also influenced cell survival markers. Tempol can be considered a beneficial therapy for PCa treatment owing to its anti-inflammatory and antiproliferative effects. Nevertheless, the action of tempol was different depending on the degree of the prostatic lesion in vivo and hormone reliance in vitro. This indicates that tempol plays a multifaceted role in the prostatic tissue environment.

Prostate histological investigation in rats exposed to bisphenol a and phytochemicals during the perinatal period and subjected to hormonal stimulus in adulthood

ABSTRACT Bisphenol A (BPA) is an environmentally dispersed chemical associated with tumor development. Phytochemicals such as indole-3-carbinol (I3C) and genistein (GEN) have chemoprotective effects on tumor cells. Thus, this study aimed to evaluate the prostatic morphological aspects of rats exposed to BPA, GEN, and I3C during the perinatal period and submitted to hormonal stimulus in adulthood. Blood was collected to obtain hormone concentrations. Slides stained with hematoxylin & eosin, and picrosirius were subjected to fractal, stereological, morphometric, and collagen quantification analysis. I3C decreased the plasma dihydrotestosterone levels, and both phytochemicals increased the plasma estrogen levels. Unlike phytochemicals, BPA did not alter any of the parameters evaluated. GEN reduced the epithelial height, while I3C increased the fractal dimension and stromal collagen. Although BPA did not alter the prostate morphology, the phytochemicals provided beneficial effects for the prostate histological organization in adult animals subjected to hormonal stimulus.

Subacute exposure to aluminum chloride causes prolonged morphological insults in the ventral male prostate and in the female prostate of adult gerbils.

Aluminum (Al) is a widespread metal in the environment, and is found in fresh or processed foods, household utensils, packaging, and medicines. In addition to its high toxicity, Al can also have estrogenic agonistic effects on target organs. Considering that the Al effects on the prostate are little known, the aim of this study was to evaluate the impact of aluminum chloride (AlCl3 ) subacute exposure on the morphophysiology of the male ventral prostate and the female prostate of adult gerbils. Furthermore, the glandular restoration capacity in face of the Al insults was evaluated in gerbils that were submitted to 30 days of recovery. Male and female gerbils were orally exposed to AlCl3 (10mg/kg) for 30 consecutive days. The animals were euthanized 1day (Al1D) or 30 days (Al30D) after the end of treatment. Prostates were dissected out and processed for structural, ultrastructural and immunohistochemical analyses. Male ventral prostates and female prostates of the Al1D group showed increased cell proliferation, glandular hyperplasia, increased secretory activity and greater androgen receptor immunoreactivity. In males, Al withdrawal (Al30D) allowed a partial recovery of the prostate, as the glandular secretory activity, and frequency of androgen receptor positive cells were similar to the control group. In females, the recuperation interval (Al30D) was not enough to restore the prostatic morphology, since the gland remained hyperplastic, proliferative, and with greater androgen and estrogen receptor immunoreactivity. These data alert to the importance of avoiding Al exposure, since this metal can have a harmful and prolonged action on the prostate.

Influence of Androgen Receptor Antagonist MDV3100 Therapy on Rats With Benign Prostatic Hyperplasia.

PurposeTo probe the effect and mechanism of androgen receptor antagonist MDV3100 on benign prostatic hyperplasia (BPH) of ratsMethodsBPH rat model was induced by testosterone propionate. Then antagomir-miR-21-3p or agomir-miR-21-3p was injected into rats before MDV3100 treatment. The prostate index was measured by weighing the wet weight of the rat prostate. The structural morphology of rat prostate was observed after hematoxylin & eosin staining. Immunohistochemistry was applied to evaluate the expression levels of Ki-6 and inflammatory cytokines (interleukin [IL]-6, IL-18, and tumor necrosis factor-α) in rat prostate tissues. Quantitative reverse transcription polymerase chain reaction was utilized for assessment of miR-21-3p expression, and Western blot for the performance of the phosphorylation levels of IKKα and p65.ResultsInjection of testosterone propionate caused increased prostate gland hyperplasia, heightened miR-21-3p level, and activated nuclear factor-kappa B (NF-κB) signaling pathway. Additionally, BPH was accompanied by inflammatory response, as evidenced by enhanced expressions of Ki-67 and inflammatory cytokines. MDV3100 exposure ameliorated BPH and suppressed miR-21-3p expression. Overexpression of miR-21-3p intensified BPH and inflammation level, while knockdown of miR-21-3p relieved BPH. The coeffect of miR-21-3p upregulation and MDV3100 subjection led to higher inflammatory response, elevated phosphorylation levels of IKKα and p65 than MDV3100 treatment alone.ConclusionsAndrogen receptor antagonist MDV3100 alleviates BPH and inflammatory response through miR-21-3p downregulation and NF-κB signaling pathway blockade.

Miniaturized optical fiber probe for prostate cancer screening.

Tissue elasticity is universally recognized as a diagnostic and prognostic biomarker for prostate cancer. As the first diagnostic test, the digital rectal examination is used since malignancy changes the prostate morphology and affects its mechanical properties. Currently, this examination is performed manually by the physician, with an unsatisfactory positive predictive value of 42%. A more objective and spatially selective technique is expected to provide a better prediction degree and understanding of the disease. To this aim, here we propose a miniaturized probe, based on optical fiber sensor technology, for mechanical characterization of the prostate with sub-millimeter resolution. Specifically, the optical system incorporates a customized Fiber Bragg Grating, judiciously integrated in a metallic cannula and moved by a robotic arm. The probe enables the local measurement of the force upon tissue indentation with a resolution of 0.97 mN. The system has been developed in such a way to be potentially used directly in vivo. Measurements performed on phantom tissues mimicking different stages of the prostatic carcinoma demonstrated the capability of our device to distinguish healthy from diseased zones of the prostate. The study on phantoms has been complemented with preliminary ex vivo experiments on real organs obtained from radical surgeries. Our findings lay the foundation for the development of advanced optical probes that, when integrated inside biopsy needle, are able to perform in vivo direct mechanical measurements with high sensitivity and spatial resolution, opening to new scenarios for early diagnosis and enhanced diagnostic accuracy of prostate cancer.

Palmitoylethanolamide/Baicalein Regulates the Androgen Receptor Signaling and NF-κB/Nrf2 Pathways in Benign Prostatic Hyperplasia.

Benign prostatic hyperplasia (BPH) is the most common benign tumor in males. Androgen/androgen receptor (AR) signaling plays a key role in the development of BPH; its alterations cause an imbalance between prostate cell growth and apoptosis. Furthermore, chronic inflammation and oxidative stress, which are common conditions in BPH, contribute to disrupting the homeostasis between cell proliferation and cell death. With this background in mind, we investigated the effect of ultramicronized palmitoylethanolamide (um-PEA), baicalein (Baic) and co-ultramicronized um-PEA/Baic in a fixed ratio of 10:1 in an experimental model of BPH. BPH was induced in rats by daily administration of testosterone propionate (3 mg/kg) for 14 days. Baic (1 mg/kg), um-PEA (9 mg/kg) and um-PEA/Baic (10 mg/kg) were administered orally every day for 14 days. This protocol led to alterations in prostate morphology and increased levels of dihydrotestosterone (DHT) and of androgen receptor and 5α-reductase expression. Moreover, testosterone injections induced a significant increase in markers of inflammation, apoptosis and oxidative stress. Our results show that um-PEA/Baic is capable of decreasing prostate weight and DHT production in BPH-induced rats, as well as being able to modulate apoptotic and inflammatory pathways and oxidative stress. These effects were most likely related to the synergy between the anti-inflammatory properties of um-PEA and the antioxidant effects of Baic. These results support the view that um-PEA/Baic should be further studied as a potent candidate for the management of BPH.

Challenge of prostate MRI segmentation on T2-weighted images: inter-observer variability and impact of prostate morphology

BackgroundAccurate prostate zonal segmentation on magnetic resonance images (MRI) is a critical prerequisite for automated prostate cancer detection. We aimed to assess the variability of manual prostate zonal segmentation by radiologists on T2-weighted (T2W) images, and to study factors that may influence it.MethodsSeven radiologists of varying levels of experience segmented the whole prostate gland (WG) and the transition zone (TZ) on 40 axial T2W prostate MRI images (3D T2W images for all patients, and both 3D and 2D images for a subgroup of 12 patients). Segmentation variabilities were evaluated based on: anatomical and morphological variation of the prostate (volume, retro-urethral lobe, intensity contrast between zones, presence of a PI-RADS ≥ 3 lesion), variation in image acquisition (3D vs 2D T2W images), and reader’s experience. Several metrics including Dice Score (DSC) and Hausdorff Distance were used to evaluate differences, with both a pairwise and a consensus (STAPLE reference) comparison.ResultsDSC was 0.92 (± 0.02) and 0.94 (± 0.03) for WG, 0.88 (± 0.05) and 0.91 (± 0.05) for TZ respectively with pairwise comparison and consensus reference. Variability was significantly (p < 0.05) lower for the mid-gland (DSC 0.95 (± 0.02)), higher for the apex (0.90 (± 0.06)) and the base (0.87 (± 0.06)), and higher for smaller prostates (p < 0.001) and when contrast between zones was low (p < 0.05). Impact of the other studied factors was non-significant.ConclusionsVariability is higher in the extreme parts of the gland, is influenced by changes in prostate morphology (volume, zone intensity ratio), and is relatively unaffected by the radiologist’s level of expertise.