Chronic Prostatic Inflammation Research Articles

YAP1 Recognizes Inflammatory and Mechanical Cues to Exacerbate Benign Prostatic Hyperplasia via Promoting Cell Survival and Fibrosis.

Chronic prostatic inflammation promotes cell survival and fibrosis, leading to benign prostatic hyperplasia (BPH) with aggravated urinary symptoms. It is investigated whether yes-associated protein 1 (YAP1), an organ size controller and mechanical transductor, is implicated in inflammation-induced BPH. The correlation between YAP1 expression and fibrosis in human and rat BPH specimens is analyzed. Furthermore, the effects of YAP1 activation on prostatic cell survival and fibrosis, as well as the underlying mechanism, are also studied. As a result, total and nuclear YAP1 expression, along with downstream genes are significantly upregulated in inflammation-associated human and rat specimens. There is a significant positive correlation between YAP1 expression and the severity of fibrosis or clinical performance. YAP1 silencing suppresses cell survival by decreasing cell proliferation and increasing apoptosis, and alleviates fibrosis by reversing epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition in prostatic BPH-1 and WPMY-1 cells. Mechanistically, inflammatory stimulus and rigid matrix stiffness synergistically activate the RhoA/ROCK1 pathway to provoke cytoskeleton remodeling, thereby promoting YAP1 activation to exacerbate BPH development. Overall, inflammation-triggered mechanical stiffness reinforcement activates the RhoA/ROCK1/F-actin/YAP1 axis, thereby promoting prostatic cell survival and fibrosis to accelerate BPH progression.

Unveiling prostatic inflammation to optimize management of lower urinary tract symptoms: a discussion with experts.

Benign prostatic obstruction (BPO) and associated lower urinary tract symptoms (LUTS) are common conditions in men, which increase in frequency and severity with age, and have a significant impact on quality of life. Chronic prostatic inflammation is increasingly being recognized as a key component of BPO. This may lead to new targets for the management of BPO/LUTS. This podcast is based on presentations from a symposium titled 'Unveiling prostatic inflammation to optimize LUTS management' held at the European Association of Urology 2023 Congress. The presenters outline evidence of a role for prostatic inflammation in the development and progression of BPO/LUTS, approaches to the identification of biomarkers of inflammation, and the implications of prostatic inflammation for the optimal management of BPO/LUTS.

The Effect Of Seven Months Of High Intensity Interval Training On Chronic Inflammation, Body Composition And Fitness In Breast, Prostate, And Colorectal Cancer Survivors

The Effect Of Seven Months Of High Intensity Interval Training On Chronic Inflammation, Body Composition And Fitness In Breast, Prostate, And Colorectal Cancer Survivors

Targeting benign prostate hyperplasia treatments: AR/TGF-β/NOX4 inhibition by apocynin suppresses inflammation and proliferation

IntroductionApocynin (Apo), an NADPH oxidase (NOX) inhibitor, has been widely used to treat various inflammatory diseases. However, the therapeutic effects of Apo on benign prostatic hyperplasia (BPH), a multifactorial disease associated with chronic inflammation and hormone imbalance, remain unknown. ObjectivesThe link between androgen signaling, reactive oxygen species (ROS), and prostate cell proliferation may contribute to the pathogenesis of BPH; therefore, the aim of this study was to identify the specific signaling pathway involved and to demonstrate whether the anti-oxidant Apo plays a role in the prevention and treatment of BPH. MethodsIngenuity pathway analysis and si-RNA transfection were conducted to demonstrate the androgen receptor (AR) and NOX4 linkage in BPH. Pathological markers of BPH were measured by H&E staining, immunoblotting, ELISA, qRT-PCR, and immunofluorescence to examine the effect of Apo. Rats stimulated with testosterone and BPH-1 cells were used as BPH models. ResultsAR and NOX4 network-mediated oxidative stress was upregulated in the BPH model. Next, we examined the effects of Apo on oxidative stress and chronic prostatic inflammation in BPH mouse models. In a testosterone-induced BPH rat model, Apo alleviated pathological prostate enlargement and suppressed androgen/AR signaling. Apo suppressed the upregulation of proinflammatory markers and promoted the expression of anti-oxidant factors. Furthermore, Apo regulated the TGF-β/Glut9/activin pathway and macrophage programming. In BPH-1 cells, Apo suppressed AR-mediated proliferation and upregulation of TGFB and NOX4 expression by alleviating oxidative stress. Apo activated anti-oxidant and anti-inflammatory systems and regulated macrophage polarization in BPH-1 cells. AR knockdown partially abolished the beneficial effects of Apo in prostate cells, indicating AR-dependent effects of Apo. ConclusionIn contrast with existing BPH therapies, Apo may provide a new application for prostatic disease treatment, especially for BPH, by targeting the AR/TGF-β/NOX4 signaling pathway.

PD02-11 THE EXTENT OF CHRONIC PROSTATIC INFLAMMATION WAS NEGATIVELY AND POSITIVELY CORRELATED WITH THE DURATION OF ALPHA-1 BLOCKERS AND 5 ALPHA REDUCTASE INHIBITORS BEFORE SURGICAL TREATMENT

You have accessJournal of UrologyCME1 Apr 2023PD02-11 THE EXTENT OF CHRONIC PROSTATIC INFLAMMATION WAS NEGATIVELY AND POSITIVELY CORRELATED WITH THE DURATION OF ALPHA-1 BLOCKERS AND 5 ALPHA REDUCTASE INHIBITORS BEFORE SURGICAL TREATMENT So Inamura, Tomochika Shinagawa, Hisato Kobayashi, Manami Tsutsumiuchi, Masaya Seki, Minekatsu Taga, Masato Fukushima, Osamu Yokoyama, and Naoki Terada So InamuraSo Inamura More articles by this author , Tomochika ShinagawaTomochika Shinagawa More articles by this author , Hisato KobayashiHisato Kobayashi More articles by this author , Manami TsutsumiuchiManami Tsutsumiuchi More articles by this author , Masaya SekiMasaya Seki More articles by this author , Minekatsu TagaMinekatsu Taga More articles by this author , Masato FukushimaMasato Fukushima More articles by this author , Osamu YokoyamaOsamu Yokoyama More articles by this author , and Naoki TeradaNaoki Terada More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003219.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Alpha 1 blockers (ABs) and 5 alpha-reductase inhibitors (5ARIs) have been used for the medical treatment of benign prostatic hyperplasia (BPH) and the patients resistant to these therapies receive surgical treatment. We previously reported that the extent of chronic prostatic inflammation was positively correlated with the obstruction of BPH patients in pressure flow study (Inamura et al. Prostate 2018). This study investigated the correlation of the duration of ABs and 5ARIs with the extent of chronic inflammation by evaluating the expression levels of high endothelial venule (HEV) in prostate tissue. METHODS: Tissue samples were obtained from BPH patients who underwent transurethral resection of the prostate (TURP) or holmium enucleation of the prostate (HoLEP). All the patients received pressure flow study before the surgery. HEV is associated with the migration of lymphocytes and is used as a marker of chronic inflammation. The magnitude of prostatic inflammation was quantified histologically by the ratio of HEV and endothelial cells using the immunohistochemistry of MECA-79 and CD34. The type and duration of medical treatment before surgery were examined on medical records. The correlation of MECA-79/CD34 ratio with the duration of ABs and 5ARIs was evaluated. RESULTS: In 148 patients, 143 patients (97%) received ABs and 33 patients (22%) received 5ARIs adding to ABs. The median duration ABs was 14 months, and the median duration of 5ARIs was 7 months. The duration of ABs was significantly negatively correlated with Bladder Outlet Obstruction Index (BOOI) in pressure flow study (correlation coefficient=-0.270 p=0.029). The duration of ABs was significantly negatively correlated with MECA-7/CD34 ratio (correlation coefficient=-0.194, p=0.030). However, the duration of 5ARIs was positively correlated with MECA-7/CD34 ratio (correlation coefficient=0.501, p=0.001). CONCLUSIONS: These results indicated that the patients who received longer treatment by ABs before surgery had lower level of obstruction and lower extent of chronic prostatic inflammation. However, the patients who received longer treatment of 5ARIs had higher extent of chronic prostatic inflammation. The long-term therapy by 5ARIs might have potential to enhance chronic inflammation in prostate tissue. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e72 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information So Inamura More articles by this author Tomochika Shinagawa More articles by this author Hisato Kobayashi More articles by this author Manami Tsutsumiuchi More articles by this author Masaya Seki More articles by this author Minekatsu Taga More articles by this author Masato Fukushima More articles by this author Osamu Yokoyama More articles by this author Naoki Terada More articles by this author Expand All Advertisement PDF downloadLoading ...

Modern concepts about chronic prostate inflammation

The review presents modern aspects of the epidemiology, pathogenesis, diagnosis, drug treatment of chronic prostatitis. We performed a comprehensive search using multiple databases. There is still no single pharmacological approach in the management of patients with chronic prostate. Future clinical trials should include a full report of their methods including adequate masking, consistent assessment of all patient-important outcomes including potential treatment-related adverse events and appropriate sample sizes.

Chronic prostatic inflammation as a prognostic marker for post-operative improvement in clinical parameters after transurethral resection of prostate

Background: Medical therapy of prostatic symptoms and reduce study on benign prostatic hyperplasia (BPH) recently demonstrated a link between histological prostatic inflammation and prostate enlargement or symptoms scores. Aims and Objectives: Prognostication of symptoms of lower urinary tract based on pathological diagnosis following transurethral resection of prostate (TURP). Materials and Methods: This was a prospective observational study. A total of 60 BPH patients who underwent TURP were studied; 30 patients in each group, BPH without inflammation (Group I), and BPH with inflammation (Group II). Pre-operative and post-operative international prostate symptom score (IPSS), overactive bladder symptom score (OABSS), and uroflowmetry were compared in both groups. Chronic prostatic inflammation was assessed by the grade (lymphocyte density), extent (lymphocyte distribution), and location of inflammation. Results: The prostate volume was significantly higher in Group II as compared to Group I (53.2±1.29 vs. 50.87±1.48). The improvement in IPSS and OABSS in each group, before and after surgery, was significant but the between-group difference was not significant. The post-operative voided volume (in ml) in Group I was 273.27±52.34 and in Group II, it was 289.47±34.25 (P=0.03). The post-operative post-void residual volume (in ml) was 21.97±2.55 in Group I and 13.28±2.11 in Group II (P=0.017). The post-operative Qmax (ml/s) in Group I was 15.41±2.1 and in Group II it was 19.28±2.11. (P=0.041). Conclusion: Surgical resection of the prostate helps in a higher degree of improvement in post-operative clinical parameters in BPH patients with inflammation.

Оценка отдаленной воспалительной и неопластической реакции тканей простаты при ее трансуретральном инфицировании уропатогенами: экспериментальное исследование

There is no convincing evidence of the persistence of acute or the development of chronic bacterial-induced prostatic inflammation in the long term when infected with various titers of the uropathogen. Along with this, controversial data are presented on the relationship between post-infectious chronic inflammation and neoplastic changes in prostate tissues.To carry out, based on the experimental data: 1) assessment of the degree of bacterial contamination and the severity of histological changes in prostate tissues on the 60th follow-up day in case of transurethral infection with various uropathogens in titers of 102,3,5 CFU/ml; 2) fundamental comparative analysis between the indicators of the inoculated test-titer and microbial load with the severity of histological changes in prostate tissues; 3) verification of neoplastic transformations in the prostate tissues during a long-term persistent bacterial-induced inflammatory process.Animal studies were conducted using FELASA protocols. Laboratory animals: 14 New Zealand rabbits. Tested uropathogens: aerobes - E. coli, S. haemolyticus, anaerobes - P. niger. Titers: 102,3,5 CFU/ml. Uropathogen inoculation technique: topical transurethral.all laboratory animals were divided into 5 groups according to the uropathogen (4 experimental, 1 control). Follow-up period: 60 days. Sacrification and autopsy of the animals were performed on day 60. Biopsies were taken from various parts of the prostate, as well as from the bladder neck and the edge of the membranous urethra. Cultural, histological and immunohistochemical (expression of p53 and Ki-67) studies of prostate tissues were conducted. Statistical data processing was performed using the GraphPad Prism 9.0 program (GraphPad Software Inc., Graphpad Holdings LLC, San Diego, CA, USA) applying descriptive and non-parametric statistics.Two individuals infected with S. haemolyticus + P. niger had a lethal outcome. The contamination of prostate tissue was determined in all cases of infection. In 88.9% of the cases, an increase in tissue microbial load was determined compared to the initial titer. Multivariate analysis of culture study values revealed the presence of intragroup differences in prostate contamination only between infection with E. coli 103 CFU/ml and E. coli 105 CFU/ml (p=0.006), as well as intergroup differences between infection with E. coli 105 CFU/ml and P. niger 105 CFU/ml (p=0.013). The histological study revealed moderate proliferative inflammation after inoculation with 102,3,5 CFU/ml in the E. coli and S. haemolyticus groups. In the case of S. haemolyticus, it was more pronounced due to the presence of persistent alterative lesion foci; in the P. niger group, mild proliferative transformations were observed in prostate tissues in all cases. The immunohistochemical study of changes determined p53 expression (10.0%) in some areas of the glandular epithelium of prostate glands (but without a positive internal control) only in case of infection with E. coli 105 CFU/ml. Areas of glandular epithelium with Ki-67 expression ( less or equal 25.0%) were visualized in all tested groups, mainly at titers of 103 and 105 CFU/ml, but the severity of proliferative activity was not high (1+). There were no foci of prostate tissue with simultaneous nuclear activity of p53 and Ki-67.Proliferative inflammation of different intensity in prostate tissues was observed after sixty days. Its severity was mainly determined by the type of infecting agent (S. haemolyticus > E. coli > P. niger) and was not dependent on the inoculated titer and the subsequent microbial load of prostate tissues. No areas of neoplastic transformation of prostate tissues were reliably identified in the case of a bacterial-induced inflammatory process in the estimated follow-up period.

Prostate Infiltration by Treg and Th17 Cells as an Immune Response to Propionibacterium acnes Infection in the Course of Benign Prostatic Hyperplasia and Prostate Cancer.

Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) belong to the most frequent diseases in ageing men. It has been proposed that prostate chronic inflammation is a risk factor for the development of both BPH and PCa. However, potential stimuli that cause or maintain inflammation in the prostate gland are still poorly characterized. Bacterial infections seems to be one of the potential sources of prostatitis. Recent studies show that Propionibacterium acnes (P. acnes) is the most prevalent microorganism in the prostate gland and may be a predisposing factor for inflammation of prostatic tissue. It indicates that P. acnes may contribute to cancer development by enhancing proinflammatory responses, as well as by modifying the prostate extracellular environment. In this review, we discuss the potential role of P. acnes in the development of BPH and PCa and highlight the importance of regulatory T CD4(+)FoxP3(+) (Treg) and Th17 cells in response to P. acnes infection in the context of both prostate diseases.

PD-L1 positive lympho-epithelial lesions in inflammatory prostate.

Ductal epithelial changes (lympho-epithelial lesions-LEL) in prostatic chronic inflammation (CI) are not well studied so far. to investigate LEL immediately adjacent to prostatic CI. We studied LEL in 144 prostatic surgical and autopsy specimens in various types of prostatic CI: NIH-category IV prostatitis (histologic prostatitis-HP), nonspecific granulomatous prostatitis (NSGP), and the reactive lymphoid infiltrates in the vicinity of benign prostatic hyperplasia (BPH) and prostate adenocarcinoma (PCa). CI is scored as low and high grade (LG, HG) according to the severity of inflammation. LEL was identified in all types of prostatic specimens and in all types of prostatic CI: in 70.9% of patients with HP; in 100% of cases with NSGP; in 68.7% and in 80% adjacent to BPH and PCa respectively. Statistical analysis showed a significant correlation of the presence of LEL with HG CI (p<0.001). LEL showed strong membranous PD-L1 expression. The study presents the first attempt to examine LEL in inflammatory human prostate. PD-L1 positive LEL have no diagnostic organ specificity, although they are a constant histological finding in HG prostatic CI. LEL, inducible after birth by CI, are an integral part of prostate-associated lymphoid tissue (PALT) and of the inflammatory prostatic microenvironment.

Propionibacterium acnes in urine and semen samples from men with urinary infection.

Propionibacterium acnes has been implicated in the pathogenesis of prostate disease as acute and chronic prostatic inflammation, benign prostatic hyperplasia and prostate cancer although it should still be clarified if Propionibacterium acnes (P. acnes) is a commensal or accidental prostate pathogen. Aiming to evaluate the pathogenic potential for genitourinary tract of Propionibacterium acnes, we investigated the frequency of P. acnes genome in urine or semen samples from men with recurrent symptoms of urinary infection and negative testing for the most common urinary tract pathogens and sexually transmitted infections (STI) agents as Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum and Ureaplasma urealyticum. The DNA extracted from urine and semen samples was analyzed for evaluating the P. acnes genome presence by real-time polymerase chain reaction (PCR). Infections were treated with vancomycin and cephalosporins antibiotics and then the search for the P.acnes genome by realtime PCR was repeated. The P. acnes qualitative real-time PCR revealed the genome in 73 out of 159 samples examined (108 urine and 51 semen). After antibiotic therapy, P. acnes was never detected. These results suggested that P. acnes genome determination should be performed in cases of chronic inflammation in the urinary tract to identify an unknown potential pathogen of genitourinary tract.

Oral administration of berberine represses macrophage activation-associated benign prostatic hyperplasia: a pivotal involvement of the NF-κB

Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases in men over the age of 50. Clinical studies have suggested that chronic inflammation is associated with BPH pathoprogression. Berberine (BB) is a natural compound found in Berberis vulgaris, Coptis chinensis and Phellodendron amurense. Although several studies have documented that BB may be effective for inflammation, the effects of the oral administration of BB on BPH are not fully understood. The effects of BB on chronic prostatic inflammation were evaluated in a testosterone-induced BPH animal model. Orally administered BB alleviated the pathological alterations induced by BPH and significantly suppressed the expression of inflammatory markers while enhancing the expression of antioxidant factors. Furthermore, BB regulated the activation of macrophages via NF-κB signaling pathway inhibition in the BPH rat model. The effects and underlying signaling pathway of BB in RWPE-1 cells exposed to macrophage conditioned medium (CM) were also demonstrated in vitro. While CM stimulation induced prostatic cell proliferation and upregulated the expression of inflammatory factors, BB exerted anti-proliferation and anti-inflammatory effects in RWPE-1 cells. These findings propose that BB suppresses androgen-dependent BPH development by targeting NF-κB-mediated pro-inflammatory signaling.

One, No One and One Hundred Thousand: Patterns of chronic prostatic inflammation and infection.

Chronic prostatic inflammation may be classified into three types that share similar symptoms and are distinguished on the basis of microbiological findings. In the present study, consecutive cases of chronic prostatic inflammation and infection were retrospectively reviewed in order to explore the clinical course and long-term outcomes. The cohort consisted of patients with symptoms of prostatitis who visited the Urology Clinic of the Tzaneion Hospital (Piraeus, Greece) between March 2009 and March 2019. The patients were subjected to the Meares and Stamey ‘4-glass’ test and patients with febrile prostatitis were evaluated with a single mid-stream ‘clean’ urine sample culture. Bacterial identification was performed using the Vitek 2 Compact system and the sensitivity test with the disc and the Vitek 2 system. A total of 656 patients with prostatitis-like symptoms with 1,783 visits for investigation and follow-up were reviewed and patients were divided into two major groups. Group 1 consisted of 549 cases with a single set of chronic prostatitis (CP)-like symptoms assessed in up to three visits. National Institutes of Health (NIH) category II CP (NIH-II) was most frequently diagnosed in those patients (37,6%). At the follow-up, 125 patients were identified as having a type of CP different from that determined initially. Group 2 (107 cases) had recurring episodes of prostatitis-like symptoms assessed or confirmed over the course of 4-18 visits. Most patients (54.2%) were initially diagnosed with NIH-II followed by disease-free periods and recurrence/reinfection or by shifts to NHI-IIIB. In conclusion, CP remains a poorly understood n medical condition characterized by a variety of clinical manifestations and by transitions between different CP classes during its course.

Prostatic Inflammation in Prostate Cancer: Protective Effect or Risk Factor?

The relationship between prostatic chronic inflammation (PCI) and prostate cancer (PCa) is unclear and controversial. Some authors reported that a history of chronic prostatitis may be correlated with PCa induction, while others associate chronic inflammation with less aggressive disease or consider inflammation as a possible protective factor against PCa. Four different types of prostatitis are known: bacterial acute prostatic inflammation, bacterial chronic prostatic inflammation, abacterial prostatitis/chronic pelvic pain syndrome, and asymptomatic prostatic chronic inflammation. Prostatic inflammation is underestimated during daily clinical practice, and its presence and degree often go unmentioned in the pathology report of prostate biopsies. The goal of this report is to further our understanding of how PCI influences the biology of PCa. We investigated the main pathogenetic mechanisms responsible for prostatic inflammation, including the cellular response and inflammatory mediators to describe how inflammation modifies the prostatic environment and can lead to benign or malignant prostatic diseases. We found that prostatic inflammation might have a pivotal role in the pathogenesis of prostatic diseases. Details about PCI in all prostate biopsy reports should be mandatory. This will help us better understand the prostatic microenvironment pathways involved in PCa biology, and it will allow the development of specific risk stratification and a patient-tailored therapeutic approach to prostatic diseases.

Identification of Altered Proteins in the Plasma of Rats With Chronic Prostatic Inflammation Induced by Estradiol Benzoate and Sex Hormones.

The cause of nonbacterial chronic prostatitis is unknown, yet its prevalence accounts for more than 90% of all prostatitis cases. Whole blood, plasma, and serum have been used to identify prostate cancer biomarkers; however, few studies have performed protein profiling to identify prostatitis biomarkers. The purpose of this study was to identify protein biomarkers altered by chronic prostatitis. To perform the study, we chemically induced chronic prostate inflammation in Sprague Dawley rats using estradiol benzoate (EB), testosterone (T), and estradiol (E) and then examined protein levels in their plasma. Plasma was collected on postnatal days (PNDs) 90, 100, 145, and 200; plasma proteins were profiled using liquid chromatography–tandem mass spectrometry. Chronic inflammation was observed in the rat prostate induced with EB on PNDs 1, 3, and 5. Rats then were dosed with T+E during PNDs 90–200 via subcutaneous implants. We identified time-specific expression for several proteins (i.e., CFB, MYH9, AZGP1). Some altered proteins that were expressed in the prostate (i.e., SERPINF1, CTR9) also were identified in the rat plasma in the EB+T+E group on PNDs 145 and 200. These findings suggest that the identified proteins could be used as biomarkers of chronic prostatitis. Further studies are needed to verify the results in human samples.

CHRONIC PROSTATITIS AND FIBROSIS OF PROSTATE. PREDISPOSING FACTORS FOR SURGICAL COMPLICATIONS

Prostatitis is an inflammatory process of the prostate, which continues to be considered one of the most common urological diseases in men under 45. Predisposing factors as trophic, microcirculatory and congestive disorders, contributes to the onset and development of the inflammatory process in the prostate and risk factors as urethral catheter, urethrocystoscopy, endoscopic surgery for infection and deterioration of the integrity of the urethral epithelium. The purpose of this study was to determine the impact of chronic inflammation and fibrosis of prostate on urodynamics and local prostatic microcirculation and to evaluate the efficacy of medicamentous treatment. In the study were included 58 patients (with pronounced clinical symptoms as dysuria, stranguria, nocturnal pollakuria 2-4 times per night and residual urine about 50ml) that followed a course of treatment with Adenosprosin 250 mg. According to the study results, we can outline that the level of microcirculation and urodynamics impairment indicates the level of prostate fibrosis. This process in chronic prostatitis is reversible by using antifibrotic and anti-inflammatory treatment supplemented with Adenoprosin 250 mg.

Altered expression of genes identified in rats with prostatic chronic inflammation in a prostate spheroid model treated by estradiol/testosterone.

Rats are the standard model for male reproductive toxicity testing. Rat prostates are physiologically and anatomically different from those of humans. Drug and chemical toxicity testing would benefit from an in vitro model of human prostate cells. Recently, spheroids derived by three-dimensional culture of human cell lines have been used for assessing drug and chemical toxicity in vitro as they mimic in vivo environments more closely than two-dimensional culture. However, forming consistently sized, uniform spheroids is technically challenging for toxicity testing. The purpose of this study was to identify potential genetic markers for assessing prostatic toxicity in spheroids. We formed prostate spheroids using agarose-coated plates seeded with human primary prostate epithelial cells. Prostate spheroids were treated with either 17β-estradiol (E2) or testosterone (T) on days 2-7 of culture. Samples were harvested on culture day 7. qPCR was used to examine gene expression levels previously identified in rats with chronic inflammation exposed to estradiol benzoate, E2 and/or T. Changes in some gene expression levels were observed in the spheroids treated with E2 or T. We found that treatment with 1 nM E2 and/or 10 μM T significantly altered spheroid proliferation and viability, as well as the expression levels of genes including Nanog homeobox (NANOG), C-C motif chemokine ligand 2 (CCL2) and bone morphogenetic protein receptor type 2 (BMPR2). Further studies using biologically active molecules with prostatic toxicity are needed to verify the results and to determine whether gene expression changes in the spheroid are specific to E2 or T treatment.

Clinical Evidence of Effective Therapy for Prostate Inflammation Based on a Combination of Macrolides and Men’s Pads

Prostatitis is a widespread disease associated with pelvic pain syndrome, which is characterized by pelvic pain, various urinary symptoms, and possible sexual dysfunction. An adequate therapy requires schemes for chronic prostatitis that affects, among other things, the atypical causative agents. We investigate a therapy for prostate inflammation consisting in a combination of macrolides with the usage of men’s pads for underwear during the treatment. We demonstrate the efficacy of this therapy on a group of patients with chronic prostatitis. The group of patients under this combination therapy exhibits better recovery dynamics compared to the group of patients who were treated only by macrolides. We observe a statistically significant (p-value < 0.01) difference between the two groups in the data from three sections of the NIH-CPSI questionnaire, which concerned pain, symptoms of impaired urination, and quality of life. The number of patients with soreness of the prostate, with the presence of bacteria and leukocytes in the prostate gland secretion, and with the presence of microorganisms in the PCR tests after treatment was lower in the combination therapy group compared to the macrolide group. The obtained results demonstrate that the use of macrolides in combination with the use of men’s pads in the treatment of chronic prostate inflammation, including “abacterial” prostatitis, is promising. More generally, our results highlight the importance of flexible and individual approaches to the treatment of chronic prostatitis.

Histopathological pattern of prostate diseases in Yola, Nigeria: A five-year review

Background: This was a five-year retrospective study aimed at analyzing all prostate biopsies submitted to the Department of Pathology, Federal Medical Centre, Yola. It will also serve as a baseline or reference study for subsequent related research in the future. Materials and Methods: All cases registered as prostate diseases within the study period were extracted from the departmental records, comprising bench books and histology reports. The age of the patients, histological diagnosis, and specimen types or surgical procedures (core biopsy, transurethral resection of prostate, or prostatectomy) were retrieved as well. All the slides corresponding to the extracted registered prostate cases received in the department between January 2012 and December 2016 were retrieved, then reviewed microscopically and analyzed afterward. Results: A total of 634 prostate tissues were submitted for histology during the study period. 63.6% (403) of these specimens were prostatectomy, whereas the remaining were core biopsies. Almost all the cases (436) analyzed occurred in men 40 years and above and predominantly in the 7th and 8th decades. Nodular hyperplasia was the most prevalent prostatic disease seen over the study period accounting for 542 cases (85.5%). The second in frequency was prostatic adenocarcinoma constituting 14% (89) of the total cases. Two cases of high-grade prostate intraepithelial neoplasia and a case of chronic prostatic inflammation were also seen. Conclusion: This study has shown that prostate diseases are most prevalent in the 6th through 9th decades of life, with nodular hyperplasia being the most common lesion of the prostate.

Chronic Baseline Prostate Inflammation is Associated with Lower Tumor Grade in Men with Prostate Cancer on Repeat Biopsy: Results from the REDUCE Study.

We investigated whether baseline acute or chronic prostate inflammation among men with initial negative biopsies for prostate cancer was associated with cancer grade in 2-year repeat biopsies. Retrospective analyses were conducted of 889 men aged 50 to 75 years old with negative baseline prostate biopsy and 2-year repeat biopsy positive for prostate cancer in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study. Acute and chronic prostate inflammation and cancer grade were determined by central pathology during the REDUCE study. The association of inflammation in baseline and 2-year repeat biopsy and prostate cancer grade in 2-year repeat biopsy was evaluated with Student's t-test, chi-squared test and multivariable logistic regression. Chronic, acute inflammation and both were detected in 533 (60%), 12 (1%) and 85 (10%) baseline biopsies, respectively. Presence of acute and chronic inflammation were significantly associated with each other (p <0.001). Both types of inflammation were unrelated to race, body mass index, prostate specific antigen or digital rectal exam. At the 2-year biopsy, 621 (70%) tumors were low grade (Gleason scores 2-6) and 268 (30%) were high grade (Gleason scores 7-10). In univariable and multivariable analyses, men with baseline chronic inflammation had significantly fewer high grade tumors (univariable OR 0.64, 95% CI 0.47-0.87, p=0.004; multivariable OR=0.68, 95% CI0.50-0.93, p=0.016) than those without baseline chronic inflammation. Baseline acute inflammation was not associated with tumor grade (univariable OR 0.74, 95% CI 0.45-1.20, p=0.22; multivariable OR 0.78, 95% CI 0.48-1.29, p=0.34). Chronic inflammation in a negative biopsy was associated with lower prostate cancer grade among men with cancer on follow-up 2-year biopsy.