Prostatic Acid Phosphatase Research Articles

Inhibitory Effect of Artemisinin on Testosterone Propionate Induced Benign Prostatic Hyperplasia.

Benign prostate hyperplasia [BPH] is an abnormal growth of prostate observed commonly in elderly males. Artemisinin has been reported to reduce the levels of testosterone. This study is designed to evaluate the efficacy of Artemisinin on testosterone propionate [TP] induced benign prostate hyperplasia. Male Wistar albino rats [n=24] were separated into four groups of six rats each. Group I served as control and distilled water using tween 80 as an emulsifying agent was administered subcutaneously. BPH was induced by testosterone propionate 3mg/kg [Group II], S.C. daily for 28 days. Group III was BPH + Finasteride treated group (10mg/kg orally for 28 days) and BPH + Artemisinin treated group (Group IV) (50 mg/kg orally for 28 days). The study results showed significantly high levels of serum prostatic acid phosphatase (PAP), lactate dehydrogenase (LDH) and an elevation in prostate weight and prostatic index in Group II (BPH) when compared with Group I. The histopathological examination showed an increase in the epithelial proliferation of prostatic cells with involutions protruding into the lumen in BPH group when compared to the normal group. Treatment with Artemisinin (50 mg/kg) reduced the levels of PAP, LDH, prostate weight and prostatic index to a significant extent and restored the histoarchitectural features of the cells. The present study concludes that Artemisinin is efficacious in testosterone propionate induced BPH. This could be attributed, at least partly, to its anti-inflammatory property or its role in testosterone level reduction or as a Vitamin D receptor modulator.

Therapeutic ISCOMATRIX™ adjuvant vaccine elicits effective anti-tumor immunity in the TRAMP-C1 mouse model of prostate cancer.

Cancer vaccine development has proven challenging with the exception of some virally induced cancers for which prophylactic vaccines exist. Currently, there is only one FDA approved vaccine for the treatment of prostate cancer and as such prostate cancer continues to present a significant unmet medical need. In this study, we examine the effectiveness of a therapeutic cancer vaccine that combines the ISCOMATRIX™ adjuvant (ISCOMATRIX) with the Toll-like receptor 3 agonist, polyinosinic–polycytidylic acid (Poly I:C), and Flt3L, FMS-like tyrosine kinase 3 ligand. We employed the TRAMP-C1 (transgenic adenocarcinoma of the mouse prostate) model of prostate cancer and the self-protein mPAP (prostatic acid phosphatase) as the tumor antigen. ISCOMATRIX™–mPAP–Poly I:C–Flt3L was delivered in a therapeutic prime-boost regime that was consistently able to achieve complete tumor regression in 60% of animals treated and these tumor-free animals were protected upon rechallenge. Investigations into the underlying immunological mechanisms contributing to the effectiveness of this vaccine identified that both innate and adaptive responses are elicited and required. NK cells, CD4+ T cells and interferon-γ were all found to be critical for tumor control while tumor infiltrating CD8+ T cells became disabled by an immunosuppressive microenvironment. There is potential for broader application of this cancer vaccine, as we have been able to demonstrate effectiveness in two additional cancer models; melanoma (B16-OVA) and a model of B cell lymphoma (Eµ-myc-GFP-OVA).Electronic supplementary materialThe online version of this article (10.1007/s00262-020-02597-6) contains supplementary material, which is available to authorized users.

SUN-143 Prostatic Acid Phosphatase Is Not Regulated by Androgens During Prostate Development and Tumorigenesis

INTRODUCTION: Prostatic acid phosphatase (PAP) is a soluble factor secreted by prostate luminal epithelial cells. PAP expression correlates with prostate cancer (PCa) bone metastases and poor survival. The androgenic regulation of PAP in prostate development and tumorigenesis is not fully understood. We investigated the relationship between PAP and androgens in human prostate specimens and in vivo. HYPOTHESIS AND OBJECTIVES: We hypothesized that PAP expression was independent of androgens. Our objectives were to determine the immunohistochemical expression of PAP in human fetal prostate tissue, human PCa bone metastases, and xenograft and surgical castration mouse models. METHODS: Immunohistochemical staining for PAP and three androgen-regulated proteins, the Androgen Receptor (AR), Prostate-Specific Antigen (PSA), and ETS-related gene (ERG) protein, was carried out on human fetal prostate (9.5, 11.5, 13, 16.5, 18 and 20 weeks of gestational age), archival human PCa bone metastases, and PCa mouse models. For xenograft studies, PAP-expressing PCa cell lines, LNCaP, C42B, and VCaP cells, were inoculated subcutaneously into SCID mice. A castration study with surgical or sham castration was performed after VCaP tumors were palpable. Mouse tumor growth and weight were measured biweekly, and tumor tissue isolated after mouse sacrifice. RESULTS: PAP expression was observed in the fetal prostate as early as 11.5 weeks of gestational age. Strong PAP expression was noted in all human PCa bone metastases examined, both treatment-naive and castrate-resistant (n=10). However, AR and ERG expression was absent in two of four castrate-resistant specimens. PSA was weakly expressed in human castration-resistant bone metastatic prostate specimens. In vivo, PAP expression was observed in all tumor models; however, the expression of PAP differed among androgen-sensitive models; LNCaP (low PAP), C42B (moderate PAP) and VCaP (high PAP). Castrated VCaP tumors underwent tumor stasis and were significantly smaller compared to intact mice. Strong expression of PAP was observed after castration. In contrast, AR, PSA, and ERG expression were reduced in castrated VCaP tumors compared to tumors from intact mice. Double staining of tumors for PAP and AR demonstrated a population of cells that were positive for PAP but negative for AR expression located in hypoxic areas near necrosis. CONCLUSIONS: Our findings demonstrated that PAP is expressed early in normal human fetal prostate development prior to the secretion of significant androgens or expression of AR. In mouse xenografts and human PCa bone metastases, androgens did not significantly regulate PAP expression. These data demonstrate that PAP is a marker of early progenitor cells in the normal prostate and is persistently expressed after castration. PAP may be a suitable target for the treatment of castration-resistant metastatic disease.

MP06-07 CHRONIC EXPOSURE TO MICROCYSTIN-LEUCINE-ARGININE PROMOTED PROLIFERATION OF PROSTATE EPITHELIAL CELLS RESULTING IN BENIGN PROSTATIC HYPERPLASIA

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology (MP06)1 Apr 2020MP06-07 CHRONIC EXPOSURE TO MICROCYSTIN-LEUCINE-ARGININE PROMOTED PROLIFERATION OF PROSTATE EPITHELIAL CELLS RESULTING IN BENIGN PROSTATIC HYPERPLASIA Haixiang Qin*, Chun Pan, Xiaodong Han, and Hongqian Guo Haixiang Qin*Haixiang Qin* More articles by this author , Chun PanChun Pan More articles by this author , Xiaodong HanXiaodong Han More articles by this author , and Hongqian GuoHongqian Guo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000820.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: With a combination of factors including global warming and lake eutrophication, mass proliferation of cyanobacteria and release of cyanotoxins including Microcystins (MCs), have drawn a growing public concern. MC-leucine-arginine (MC-LR), as the most common and deleterious variant among all structural analogues of MCs, has been reported to cause male reproductive dysfunction. However, its toxic effects on prostate, which is the largest accessory organs in adult male and plays a pivotal role in reproductive systems, have not been investigated in detail, as well as the underlying molecular mechanisms. METHODS: Herein, we investigated the toxic effects of chronic exposure to low-dose of MC-LR on the structure and function of prostate in vivo. Male BALB/c mice aged 6-weeks were divided into 10 groups with 10 mice in each group. The experiment groups were given drinking water containing 1 μg/L, 10 μg/L, 20 μg/L, or 30 μg/L MC-LR for 90 or 180 consecutive days. In addition, an immortalized prostate epithelial cell line, RWPE-1, was also applied to investigate the toxic effects and the molecular mechanisms of MC-LR exposure to the prostate epithelial in vitro. RESULTS: We observed that MC-LR dissolved in drinking water could be transported into the stromal and epithelial cells of mouse prostate. Following exposure to low-dose of MC-LR for 90 days or 180 days, focal hyperplasia as well as prostate inflammation were observed in the mouse prostate. Moreover, increased levels of prostate specific antigen (PSA) and prostate acid phosphatase (PAP) in the serum of mice following chronic exposure to MC-LR were detected. Mechanistically, treatment with MC-LR at low levels induced upregulation of forkhead box protein M1 (FOXM1) in RWPE-1 cells, which then resulted in PSA elevation. Furthermore, MC-LR also increased the expression of CyclinD1 via FOXM1/Wnt/β-catenin signaling in the epithelial cells, promoting cell proliferation and resulting in prostate hyperplasia. As a foreign substance, MC-LR was also found to induce immune reaction by promoting production of pro-inflammatory cytokines and chemokines mediated via NF-κB pathway. CONCLUSIONS: To the best of our knowledge, this is the first study to illustrate that chronic exposure to low dose of MC-LR could induce prostatic hyperplasia and prostatitis in mice. Our work involving the regulatory mechanisms may provide a new perspective in developing new diagnosis and treatment strategies for MC-LR-induced prostatic toxicity. Source of Funding: This work was supported by National Natural Science Foundation of China (31370524, 21377052, and 31670519) and Fundamental Research Funds for the Central Universities (021414380332). © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e53-e53 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Haixiang Qin* More articles by this author Chun Pan More articles by this author Xiaodong Han More articles by this author Hongqian Guo More articles by this author Expand All Advertisement PDF downloadLoading ...

Putting the Pieces Together: Completing the Mechanism of Action Jigsaw for Sipuleucel-T.

Sipuleucel-T is an autologous cellular immunotherapy that induces an immune response targeted against prostatic acid phosphatase (PAP) to treat asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. In the phase III IMPACT study, sipuleucel-T was associated with a statistically significantly increased overall survival (OS) (median = 4.1 months) vs placebo. Patients with baseline prostate-specific antigen levels in the lowest quartile (≤22.1 ng/mL) exhibited a 13-month improvement in OS with sipuleucel-T. Together, this led sipuleucel-T to be approved and recommended as first-line therapy in various guidelines for treatment of metastatic castration-resistant prostate cancer. This review discusses the varied findings about the mechanisms of action of sipuleucel-T, bringing them together to form a more coherent picture. These pieces include inducing a statistically significant increase in antigen-presenting cell activation; inducing a peripheral immune response specific to the target (PAP) and/or immunizing (PA2024) antigens; stimulating systemic cytotoxic T-lymphocyte activity; and mediating antigen spread (ie, increased antibody responses to secondary proteins in addition to PAP and PA2024). Each of these pieces individually correlates with OS. Sipuleucel-T also traffics T cells to the prostate and is associated with long-term immune memory such that a second course of treatment induces an anamnestic immune response. Prostate cancer does not have a strongly inflamed microenvironment, thus its response to immune checkpoint inhibitors is limited. Because sipuleucel-T is able to traffic T cells to the tumor, it may be an ideal combination partner with immunotherapies including immune checkpoint inhibitors or with radiation therapy.

A STUDY ON PRECLINICAL SAFETY AND EFFICACY OF MCP I CONJUGATED GOLD NANOPARTICLES BASED ORAL CONTRACEPTIVE USING BIOMARKERS OF REPRODUCTIVE TISSUES AND BLOOD SERUM OF MALE ALBINO WISTAR RATS

Characterized MCP I fraction of Carica papaya seeds is being considered a potential contraceptive agent. Utilization of gold nanoparticles as a carrier molecule enhanced its targeted bioavailability, biocompatibility, in vitro stability against blood serum and pH gradient. In this study, preclinical safety and efficacy were assessed employing concerned biomarkers of blood serum and excised reproductive tissues for further approval of this nanoformulation. Experimental groups A, B and C were consists of vehicle control, orally treated with MCP I (50 mg/kg body wt./day) and MCP I conjugated gold nanoparticle (200µg/kg body wt./day) containing nine male albino Wistar rats in each. Three animals were sacrificed monthly interval during 90 days of investigation period. No significant differences were examined in markers of blood serum i.e., cholesterol, creatinine, lactate dehydrogenase, creatine kinase, bilrubin, urea, triglyceride, HDL and concentrations of testosterone, luteinizing hormone and follicle stimulating hormone except drastic reduction in SGOT (p is less than 0.001) and SGPT (p is less than 0.05; p is less than0.01; p is less than 0.001) in group C. The glycogen, cholesterol and lactate dehydrogenase level in testicular tissues, sialic acid and fructose corresponded to epididymal and seminal vesicles, respectively, demonstrated insignificant changes. Significant diminution was recorded in the level of L-carnitine and α-glucosidase at 60 days in group B (p is less than 0.05) and 30 days in group C (p is less than 0.01; p is less than 0.001) of epididymal tissues. Prostatic acid phosphatase was increased (p is less than 0.05; p is less than 0.01) in group C. While antioxidant biomarkers in testicular tissues viz., lipid peroxidase, superoxide dismutase, reduced glutathione and catalase were revealed insignificant alteration. Thus, status of biomarkers indicate that synergistic effect of MCP I conjugated gold nanoparticle was found to be targeted, safe and effective for oral contraception in male albino rats at highly reduced dosage compared to pure MCP I treated animals which may open new avenues for clinical development.

Reflection of Heart Rate Physiological Regulation Parameters in the Urinary Proteome in Healthy Young Males

Urine chromatography–mass spectrometry and a heart rate variability (HRV) analysis were performed in 13 healthy males (age 28 ± 4 years, height 174 ± 1 cm, weight 67.9 ± 1.5 kg). Mathematical and bioinformatics analyses identified the proteins that are associated with the condition of the cardiovascular system and the autonomic regulation of the heart rate in the total protein aggregate. The set included serotransferrin, tyrosine-protein kinase receptor UFO, prostatic acid phosphatase, secreted and transmembrane protein 1, cell adhesion molecule 4, galectin-3-binding protein, immunoglobulin heavy constant alpha 1, matrix remodeling-associated protein 8, and biotinidase. Associations were for the first time studied for protein markers of the heart rate autonomic regulation. Proteomics data were used to describe the indicators of the heart rate physiological regulation in the urine proteome of healthy young males.

CD73 or CD39 Deletion Reveals Different Mechanisms of Formation for Spontaneous and Mechanically Stimulated Adenosine and Sex Specific Compensations in ATP Degradation.

Adenosine is important for local neuromodulation, and rapid adenosine signaling can occur spontaneously or after mechanical stimulation, but little is known about how adenosine is formed in the extracellular space for those stimulations. Here, we studied mechanically stimulated and spontaneous adenosine to determine if rapid adenosine is formed by extracellular breakdown of adenosine triphosphate (ATP) using mice globally deficient in extracellular breakdown enzymes, either CD39 (nucleoside triphosphate diphosphohydrolase 1, NTPDase1) or CD73 (ecto-5'-nucleotidase). CD39 knockout (KO) mice have a lower frequency of spontaneous adenosine events than wild-type (WT, C57BL/6). Surprisingly, CD73KO mice demonstrate sex differences in spontaneous adenosine; males maintain similar event frequencies as WT, but females have significantly fewer events and lower concentrations. Examining the mRNA expression of other enzymes that metabolize ATP revealed tissue nonspecific alkaline phosphatase (TNAP) was upregulated in male CD73KO mice, but not secreted prostatic acid phosphatase (PAP) or transmembrane PAP. Thus, TNAP upregulation compensates for CD73 loss in males but not in females. These sex differences highlight that spontaneous adenosine is formed by metabolism of extracellular ATP by many enzymes. For mechanically stimulated adenosine, CD39KO or CD73KO did not change stimulation frequency, concentration, or t1/2. Thus, the mechanism of formation for mechanically stimulated adenosine is likely direct release of adenosine, different than spontaneous adenosine. Understanding these different mechanisms of rapid adenosine formation will help to develop pharmacological treatments that differentially target modes of rapid adenosine signaling, and all treatments should be studied in both sexes, given possible differences in extracellular ATP degradation.

A phase Ib/II, open-label, platform study evaluating the efficacy and safety of AB928-based treatment combinations in participants with metastatic castrate-resistant prostate cancer.

TPS272 Background: The tumor microenvironment contains high levels of immunosuppressive adenosine, which binds to and activates the A2a and A2b receptors (R) on immune cells, resulting in an ineffective anti-tumor immune response. Extracellular adenosine is primarily produced by the enzyme CD73. In prostate cancer (PC), the activity of prostatic acid phosphatase produces additional adenosine. AB928 is the first clinical-stage small molecule dual antagonist of both A2aR and A2bR, which is highly potent, pharmacodynamically active, and has been well tolerated in dose escalation studies as a single agent or in combination with chemo/immunotherapy. Targeting the adenosine pathway in combination with standard of care regimens may have a more profound effect on activating and inducing sustained anti-tumor immunity. Methods: This Phase 1b/2, open-label, multi-cohort platform study will evaluate the efficacy and safety of AB928 combination therapy in participants with metastatic castrate resistant PC (mCRPC). Each cohort will independently assess AB928 plus AB122 (anti-PD-1 antibody) in combination with standard of care (SOC; enzalutamide, docetaxel) or AB928 plus AB680 (CD73 inhibitor) with or without AB122. Cohort eligibility is informed by prior treatment history. In Ph1b, up to 15 participants will receive investigational products at the single-agent recommended dose with SOC per label guidance. Provided safety and activity stopping criteria are not met, further accrual will proceed in Ph2 and, depending on treatment cohort, may involve randomization to enzalutamide or docetaxel; crossover to experimental therapy will be allowed following progression on control treatment. Investigator-assessed antitumor response (radiologic, prostate specific antigen) will follow PCWG3 criteria. Conclusions: This Ph1b/2 study is the first to target the adenosine axis using a dual A2aR/A2bR antagonist (AB928) together with a small molecule CD73 inhibitor (AB680), anti-PD-1 antibody (AB122), and SOC for mCRPC. Study enrollment is proceeding in the United States; results will be shared in upcoming scientific conferences.

Phase II trial of a DNA vaccine encoding prostatic acid phosphatase (pTVG-HP) and nivolumab (Nivo) in patients (pts) with nonmetastatic, PSA-recurrent prostate cancer (PCa).

TPS273 Background: Radical prostatectomy (RP) and radiation therapy (RT) are the gold standard, curative intent treatment for pts with presumed organ-confined PCa. However, about one third of these pts will have progressive or metastatic disease at 10 years (yr). Pts with PSA recurrence without radiographic evidence of metastatic (m) PCa (stage M0) will ultimately develop radiographically apparent mPCa within a median of 8 yr. Pts with rapid PSA doubling time (DT) have a markedly shorter time to mPCa and death. Utilizing an immunotherapeutic approach could utilize the sensitivity and specificity of the immune system to treat microscopic disease and potentially avoid or postpone androgen deprivation therapy (ADT) and its unwanted side effects. Methods: In this single arm, two-stage phase II trial, a total of 21-41 PCa pts with PSA only progression (4 rising PSA with final PSA ≥ 2 ng/mL) after initial RP for presumed organ-confined disease who have no radiographic evidence of mPCa in conventional imaging (CT and bone scan) will be enrolled. Pts with small cell or other variant PCa, or history of ADT other than concurrent with RT are excluded. All pts will be treated with pTVG-HP 100 μg intradermally (id) and Nivo 240 mg IV every (Q) 2 weeks (w) x6, and then pTVG-HP 100 μg id and Nivo 480 mg IV Q4w x9 beginning w12 on study. Pts with PSA on w4 > PSA on day 1 will additionally receive rhGM-CSF 208 μg id, as a vaccine adjuvant, Q2w x4 beginning w4 on study. Pts will be treated until progression or up to a total of 1 yr. Response will be monitored by CT and bone scan Q6 months or as clinically indicated. Primary endpoints are safety and tolerability of this combination and PSA complete response rate (PSA < 0.2 ng/mL). Key secondary endpoints are 2-yr metastasis-free survival, median radiographic progression-free survival, PSA response rate (≤50% of baseline), and changes in PSA DT. Elicited antigen-specific T-cell and/or IgG response and its correlation with PSA response will be explored. Bone mets not detected by conventional imaging and their association with response will be evaluated by Quantitative Total Bone Imaging (QTBI) by NaF PET/CT. Updated enrollment will be presented. Clinical trial information: NCT03600350.

Selection and validation of suitable reference genes for quantitative real time PCR analysis of gene expression studies in patchouli under Meloidogyne incognita attack and PGPR treatment

Patchouli (Pogostemon cablin) is an economically important aromatic plant and is often vulnerable to nematode attack (Meloidogyne incognita). The application of PGPR has tremendously changing disease management approach in plants and a systematic understanding the molecular mechanism behind it is needed to control over the disease more precisely. Since, qRT-PCR is the most frequently used molecular tools in studying molecular mechanism but is greatly dependent upon suitable reference or housekeeping genes. This study is aim to select suitable reference genes for qRT-PCR experiments in patchouli under the condition of nematode attack and PGPR treatments. Expression pattern of six reference genes (Actin, EF1, ACP, COX3, GAPDH and Pat18S) were statistically analyzed and validated using different algorithms viz., ΔCt, BestKeeper, GeNorm, NormFinder and RefFinder. The result showed that the Actin and ACP are the most suitable reference genes and the combination of ACP &GAPDH gene pairs can also be used whenever the experiment needed.

Bovine papillomavirus prostate cancer antigen virus-like particle vaccines are efficacious in advanced cancers in the TRAMP mouse spontaneous prostate cancer model.

Prostate cancer is a candidate for immunotherapy because cancer cells express tissue-specific proteins that can be therapeutic targets. However, immune checkpoint inhibitors and active immunization have performed poorly in clinical trials. We developed a novel virus-like particle (VLP) vaccine composed of bovine papillomavirus L1 protein engineered to display surface docking sites. We decorated VLPs with peptides encoding T cell epitopes from two prostate cancer-associated tumor antigens, prostate stem cell antigen (PSCA), and prostatic acid phosphatase (PAP-1 and PAP-2), and a neo-antigen, stimulator of prostatic adenocarcinoma-specific T cells (SPAS-1). The VLP vaccines induced a mean frequency of antigen-specific IFN-γ secreting CD8 + T cells of 2.9% to PSCA, 9.5% to SPAS-1, 0.03% to PAP-1, and 0.03% to PAP-2 in tumor-bearing TRAMP mice. We treated TRAMP mice at 19-20weeks of age, when mice have advanced stages of carcinogenesis, with either VLP vaccine, anti-PD1 antibody, or combination immunotherapy. The VLP vaccine alone or in combination with anti-PD1 antibody significantly reduced tumor burden, while anti-PD1 antibody had a modest non-significant therapeutic effect. All treatments significantly increased CD3 + and CD8 + T cell infiltration into tumor tissue compared to control mice, and combination therapy resulted in significantly greater CD3 + and CD8 + T cell infiltration than monotherapy. Reduction in tumor burden in vaccine-treated mice was inversely correlated with CD8 + T cell numbers in tumor tissue. No other immunotherapy has shown efficacy in this animal model of advanced prostate cancer, making bovine papillomavirus VLPs an attractive vaccine technology to test in patients with metastatic prostate cancer.

Membrane Disruption and Peptide/Lipid Co-Assembly by the Amyloid-Forming Peptide, PAP248-286

Both amyloid-forming and antimicrobial peptides (AMPs) are membrane active, displaying a variety of membrane-disrupting and -remodeling activities including membrane leakage, vesicle fusion, and vesicle aggregation. The cytotoxicity of membrane disrupting pre-fibrillar oligomers underlies the pathological activity of amyloid-forming peptides. Conversely, the disruption and aggregation of microbial membranes by AMPs is critical to their function in an innate immune response. Therefore, studying the factors driving the membrane activity of these peptides may be valuable in understanding both normal function and diseased states. We focus our studies on an amyloidogenic fragment of prostatic acid phosphatase (PAP248-286). In its amyloid state, this peptide is termed “semen-derived enhancer of viral infection” (SEVI), and greatly increases HIV infectivity. It is also thought to play functional roles in the antimicrobial activity of seminal fluid and sperm clearance during fertilization. Using liposomes as model membranes and biophysical tools including negative stain electron microscopy, dynamic light scattering, and single particle fluorescence burst analysis, we have demonstrated that PAP248-286 displays dramatic membrane remodeling activities, as it can form large, fibrillar lipid-peptide co-aggregates that are distinct from SEVI amyloid and form much more readily. We have also found that PAP248-286 is a potent membrane disruptor. Using fluorescence dequenching experiments we have determined that PAP248-286 disrupts liposomes in a charge and dose dependent manner. We have also developed new approaches to improve the fitting and analysis of complex time-correlated single photon counting (TCSPC) experimental data, which has allowed us to characterize its leakage mechanism. Our work to elucidate the determinants of PAP248-286 membrane activity is not only important for understanding its biological activities, but also provides a framework for studying the membrane activity of other biologically important amyloid-forming and antimicrobial peptides.

The effect of Metapanax delavayi leaf extract on testosterone‐induced benign prostatic hyperplasia in rats

• MD-T showed an anti-BPH effect in model rats. • MD-E is the active component of MD-T on anti-BPH. • MD-T and MD-E show regulating hormone, anti-inflammation and antioxidant effects. • MD-E mainly consists of saponins and sesquiterpenes. The leaves of Metapanax delavayi (Araliaceae) have been consumed as a common wild vegetable and herbal tea in China. In this study, we evaluated the effect of M. delavayi leaves aqueous extract (MD-T) and its fractions (MD-W and MD-E) on benign prostatic hyperplasia (BPH) in testosterone propionate (TP) induced rat model based on folk applications. The results showed that MD-T and MD-E could significantly reduce the prostate weight, prostate index, and serum level of prostate acid phosphatase (PAP) in BPH rats and improve the tissue morphology of the prostate. They mainly played roles in regulating the sex hormone level, reducing the levels of inflammatory factors and improving the antioxidant levels of prostate tissue. UPLC-Q-TOF-MS analysis showed that the main components of MD-E were saponins and sesquiterpenes, and the content of liangwanoside II was the highest. Our findings suggested that MD-T and its fraction MD-E showed an anti-BPH effect.

Changes in the Serum Prostatic Biomarkers During the Treatment of Benign Prostatic Hyperplasia with a 5alpha-reductase Inhibitor: Finasteride

The monitoring of serum prostatic biomarkers during the treatment will help clinicians to know the statement of the response to finasteride in dogs affected by benign prostatic hyperplasia (BPH). The present study was aimed to assess changes in the serum canine prostate-specific esterase (CPSE), prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), testosterone, dihydrotestosterone (DHT) and prostate volume evaluation using ultrasonographic examination during the treatment with finasteride in BPH-induced dogs. Twenty dogs were divided into 4 groups (n = 5): BPH + finasteride group, dogs which were induced for BPH and received oral finasteride once daily for 1 month; BPH group, dogs which were induced for BPH and received placebo; finasteride group, normal dogs which received finasteride; and normal group, normal intact dogs which did not receive treatment. Blood sampling and ultrasonography examination were performed on days 0, 14, and 28. The administration of finasteride led to a significant decrease in the concentration of the prostate-specific biomarkers (PSA, CPSE), DHT, testosterone, and the volume of the prostate in BPH + finasteride group compared with the BPH group during 1 month. Interestingly, the PAP concentration did not change in the BPH-induced dogs and in dogs treated with finasteride. It seems that the monitoring of serum PSA and CPSE levels and ultrasonographic examination of the prostate are useful methods for following up the response to finasteride treatment in dogs affected by BPH.

Study to Evaluate HER2-neu Expression in Different Histopathological Grades of Prostatic Carcinoma in a Tertiary Care Centre, Bareilly

Introduction: Prostate cancer is the second most common neoplasm among men around the world. Two routinely used immunocytochemical markers for prostatic epithelium are Prostatic Acid Phosphatase (PAP) and Prostatic Specific Antigen (PSA). Various other markers like Prostate-Specific Membrane Antigen (PSMA), androgen and progesterone receptors, HER2-neu, low molecular weight keratin, etc., are also used. HER2-neu overexpression has been implicated in tumorigenesis and has been correlated with a poor prognosis for patients with breast cancer, ovarian cancer, and gastric cancer. Use of Trastuzumab for the treatment of breast carcinoma has improved prognosis in HER2-neu positive cases. Recent studies have suggested the correlation of HER2-neu overexpression with higher grades of prostate cancer. Aim: To study HER2-neu expression in different histopathological grades of prostatic carcinoma. Materials and Methods: A prospective study was carried out on 41 histopathologically proven cases of prostatic carcinoma in Pathology Department of SRMSIMS, Bareilly over a period of one year and six months (November 2017 to April 2019). Gleason grading and HER2-neu Immunohistochemistry was applied on every case and then correlated. Statistical tests were applied, statistical software Statistical Package for the Social Sciences (SPSS) version 21. Results: A 92.7% (38/41) cases were reported as Prostatic Adenocarcinoma of Non-Mucinous type. Total of 42.5% (17/40) were grouped under Grade group 5, 27.5% (11/40) cases under Grade group 3 and 10% (4/40) under Grade groups 1,2 and 4 each. Out of total, 14.6% (6/41) cases were considered as positive and 80.5% (33/41) cases were considered as negative for HER2-neu expression and 4.9% (2/41) cases were considered as equivocal (Fluorescence In Situ Hybridization (FISH) conformation required). In cases with positive HER2-neu expression, mean group grade was calculated to be 4.83±0.40 and in patients with negative HER2-neu expression, it was 3.38±1.40 (it was calculated to find correlation between group grade and HER2-neu expression). There was a significant statistical difference (p=0.00003668) found between the Gleason Group Grade in HER2-neu positive and negative patients as HER2-neu positivity is seen in higher group grades. One case was reported as neuroendocrine carcinoma in which Gleason grading was not done. Conclusion: Compared to low Gleason Group Grade carcinoma, higher percentage of HER2-neu expression was seen in high Gleason Group grade carcinoma.

Immunohistochemical Reactivity of Prostate-Specific Markers for Salivary Duct Carcinoma

Objectives: NKX3.1, a transcription factor related to androgen expression, has recently been introduced as a diagnostic marker of prostate adenocarcinoma. Salivary duct carcinoma (SDC) is typically positive for androgen receptor (AR). Therefore, we hypothesized that NKX3.1 is a new immunohistochemical marker for SDC and aimed to investigate whether NKX3.1 staining in combination with other immunomarkers of prostate carcinoma could have a diagnostic or prognostic value in SDC. Methods: Materials obtained from 42 resected SDCs were examined by immunohistochemistry using antibodies against AR, NKX3.1, α-methylacyl-CoA racemase (AMACR), prostatic acid phosphatase (PAP), and prostate-specific antigen (PSA). Results: In immunoreactivity among SDC cases, 81.0, 35.7, 58.5, 33.3, and 0% were positive for AR, NKX3.1, AMACR, PAP, and PSA, respectively. AMACR and PAP immunoreactivity rates were higher in recurrence cases than in cases with no recurrence. Conclusions: NKX3.1 expression is useful for SDC diagnosis, but decreased NKX3.1 expression was not correlated with SDC progression. The immunoreactivity of AMACR and PAP could be useful for assessing prognosis in SDC, but immunohistochemical staining of prostate-specific markers should be interpreted with caution when determining whether a metastatic tumor is of prostate origin, especially when patients have a history of SDC.

Changes in specific serum biomarkers during the induction of prostatic hyperplasia in dogs

BackgroundProstatic hyperplasia (PH) is one of the most important disorders in intact dogs. In this study, we aimed to induce PH experimentally using the combination of testosterone and estrogen and evaluate important factors associated with this disease.ResultsThe results showed that in the induction group, prostate volume and prostate specific antigen (PSA) concentration increased significantly on day 21 onwards compared to those of the control group. Canine prostatic specific esterase (CPSE) and dihydrotestosterone (DHT) concentrations increased significantly on day 42 onwards while the testosterone levels increased on day 63. In addition, prostatic acid phosphatase (PAP) concentration did not change significantly in the control and induction groups. Biochemistry profiles and hematologic factors were measured for monitoring the function of liver and kidney, and there were no adverse effects following the induction of PH.ConclusionsIt seems that testosterone and estrogen administration led to prostatic hyperplasia during 2 months. Investigating the size of the prostate, accompanied by prostate markers including CPSE, PSA, DHT, and testosterone, is helpful for the PH diagnosis. However, further studies should be carried out on PAP.

Differential seminal plasma proteome signatures of acute lymphoblastic leukemia survivors

With advances in therapeutic methods, there is a high survival rate among leukemia patients, of an extent more than 80%. However, chemotherapeutic drugs used to treat these patients have adverse effects on their overall health profile including fertility. The primary aim of this study was to identify differentially expressed proteins in seminal plasma of acute lymphoblastic leukemia (ALL) survivors compared to age-matched healthy controls, which can provide molecular basis of idiopathic infertility in such survivors. Differential proteome profiling was performed by 2D–differential in-gel electrophoresis, protein spots were identified by mass spectrometry and selective differentially expressed proteins (DEPs) were validated by western blotting and ELISA method. Out of eight DEPs identified, five proteins (isocitrate dehydrogenase 1, semenogelin 1, lactoferrin, prolactin-inducible protein, and human serum albumin) were upregulated and three (pepsinogen, prostate specific antigen and prostatic acid phosphatase) were downregulated. Expression profiles of these proteins are suggestive of reduction in semen quality in ALL survivors and can further be explored to determine their fertility status.

Treatment of experimentally induced benign prostatic hyperplasia with Tadalafil and castration in dogs

New methods are being developed for the treatment of benign prostatic hyperplasia (BPH) in dogs. The aim of the present study was to evaluate the effects of Tadalafil on the treatment of experimentally induced BPH in dogs. Twenty-five adult intact male dogs were randomly divided into five groups (n = 5): normal group; dogs induced with BPH and treated with Tadalafil (5 mg/day p.o.); dogs which received Tadalafil (5 mg/day p.o.); dogs induced with BPH and treated with castration; and dogs induced with BPH. For 4 sequential weeks, the hematologic and prostate-specific factors (dihydrotestosterone (DHT), serum prostate-specific antigen (PSA), serum prostatic acid phosphatase (PAP), and canine prostatic specific esterase (CPSE)) were measured. Significant differences were observed in the level of PSA, CPSE, and PAP concentration between the normal vs. BPH-Tadalafil, BPH-castrated, and BPH groups. Treating BPH-induced dogs with Tadalafil or castration significantly declined the serum PSA, CPSE, and PAP levels compared to those of the untreated BPH-induced group. The treatment of normal dogs with Tadalafil did not affect prostate-specific biomarkers in comparison with normal dogs. In conclusion, and according to the prostatic indices, it could be stated that Tadalafil, compared with castration, could be used for the treatment of BPH in dogs.