Prostatic Acid Phosphatase Levels Research Articles

Therapeutic Potential of 5α-Reductase Inhibitor 17-oxo-17a-aza-D-homo-5-androsten-3β-yl phenoxyacetate (17a-aza Steroid) in the Management of Prostate Cancer

Background: The present study highlights the comparative therapeutic efficacy of the newly synthesized drug 17-Oximino-5-androsten-3β-yl 4-aminobenzoate (17a-aza steroid) and finasteride for the treatment of experimentally induced prostate carcinogenesis in rats. Considering the inhibitory activity of the oximes to 5α-reductase and the role of the ester group in augmenting the anti- androgenic property, we decided to synthesize a compound with a lactam moiety in ring D and esters at 3β position of androsterone nucleus as a more potent 5α-reductase inhibitor. Methods: In this study, 30 rats were divided into six groups, viz. Group I as normal controls, Group II was treated with carcinogen N-methyl-N-nitrosourea (MNU) and hormone testosterone propionate (TP) for inducing prostate cancer, Group III rats were treated with finasteride (10mg/Kg of body weight for 8 weeks through gavage), Group IV was treated with 17a-aza steroid (10mg/Kg of body weight for 8 weeks through gavage), whereas, Group V and Group VI were given finasteride and 17a-aza steroid, respectively, with similar doses as in Group III and IV after pretreatment with a carcinogen (MNU) and hormone (TP). Results: The induction of carcinogenesis by treating animals with MNU+TP revealed a significant reduction in weight loss as compared to the normal control group, which, however, increased following 17a-aza steroid treatment. Furthermore, the study witnessed a significant improvement in prostatic biomarker, viz prostatic acid phosphatase (PAcP) in serum following finasteride and 17a-aza steroid treatment to MNU+TP treated rats. Histological investigation of prostate tissue sections of 17aaza steroid-treated prostate cancer rats showed milder hyperplastic glandular epithelium and exhibited signs of recovery as compared to carcinogen-treated rats. Conclusion: The present findings are preliminary and suggest that the 17a-aza steroid has therapeutic efficacy for the management of experimentally induced prostate cancer, as evidenced by changes in prostate weight, PAcP levels, and histology. In comparison to finasteride, further exploration is needed to assertively conclude its comparative therapeutic efficacy.

Deciphering anti–benign prostatic hyperplasia potential of liangwanoside II based on metabolite profile characterization combined with targeted network pharmacology

Ethnopharmacological relevanceMetapanax delavayi (Franch.) J.Wen & Frodin (Araliaceae), known as “liang wang cha” in China, has been used to treat prostatitis as herbal tea in folk. Recent research suggested that aqueous extract of Metapanax delavayi leaves showed an advantage in anti–benign prostate hyperplasia (BPH) activity, and liangwanoside II was the main component of the active fraction. However, the anti–BPH effect of liangwanosdie II remains to be revealed. Aim of the studyThis study aims to decipher anti–BPH potential of liangwanoside II. Materials and methodsThe anti–BPH effect was evaluated by testosterone propionate–induced BPH rats after oral administration of liangwanoside II at the doses of 30, 60 and 120 mg/kg in vivo. Then, the metabolites of liangwanoside II in rats were identified using ultra–performance liquid chromatography coupled with quadrupole tandem time–of–flight mass spectrometry (UPLC–Q–TOF–MS). Finally, the targeted network pharmacology combined with experimental verification were explored for the mechanism elucidation in vivo. ResultsLiangwanoside II exhibited an anti–BPH effect through reducing the weight of the prostate, prostate index and serum prostatic acid phosphatase level, and improving the prostate tissue morphology in BPH rats. Further, 16 metabolites of liangwanoside II in vivo were identified by UPLC–Q–TOF–MS analysis, in which the prototype compound and 4 metabolites, such as liangwanoside I and serratagenic acid could be absorbed in the plasma and then penetrate the blood–prostate barrier. Then, followed by the targeted network pharmacology and experimental verification, we found that liangwanoside II and its metabolites could jointly involve in the inhibition of the inflammation reaction and hormone imbalance, thus reducing oxidative stress damage, and restoring the balance between cell proliferation and apoptosis, which contributed to the anti–BPH effect of liangwanoside II. ConclusionThe anti–BPH potential of liangwanoside II was revealed using metabolite profile characterization combined with targeted network pharmacology, providing new insight into the development and utilization of liangwanoside II.

MP40-01 DIFFERENTIALLY EXPRESSED GLYCOPROTEINS IN PRE- AND POST- DIGITAL RECTAL EXAMINATION URINE SAMPLES FOR DETECTING AGGRESSIVE PROSTATE CANCER

You have accessJournal of UrologyCME1 Apr 2023MP40-01 DIFFERENTIALLY EXPRESSED GLYCOPROTEINS IN PRE- AND POST- DIGITAL RECTAL EXAMINATION URINE SAMPLES FOR DETECTING AGGRESSIVE PROSTATE CANCER Indu Kohaar, Yuefan Wang, Tung-Shing Mamie Lih, Naseruddin Höti, Lori Sokoll, Gregory Chesnut, Gyorgy Petrovics, and Hui Zhang Indu KohaarIndu Kohaar More articles by this author , Yuefan WangYuefan Wang More articles by this author , Tung-Shing Mamie LihTung-Shing Mamie Lih More articles by this author , Naseruddin HötiNaseruddin Höti More articles by this author , Lori SokollLori Sokoll More articles by this author , Gregory ChesnutGregory Chesnut More articles by this author , Gyorgy PetrovicsGyorgy Petrovics More articles by this author , and Hui ZhangHui Zhang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003278.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PCa) is predominantly indolent disease with a small fraction of patients undergoing metastatic progression. Therefore, it is critical to identify non-invasive diagnostic markers for the early detection of an aggressive PCa subtype. We hypothesized that non-invasive pre-digital rectal examination (pre-DRE) urine specimens harbor molecular signatures of aggressive PCa, which can help in the clinical management of the disease. Previously, we had systematically evaluated urinary glycoproteins associated with aggressive prostate cancer (AG-PCa) using post-DRE urine specimens. The goal of the study is to explore the potential of using pre-DRE urine specimens for detecting AG-CaP and validate the post-DRE findings. METHODS: This is a retrospective case cohort study based on 154 pre-DRE urine specimens collected by the Center for Prostate Disease Research under an institutional review board approved protocol from men undergoing diagnostic biopsy. We performed an optimized quantitative mass spectrometric analysis to evaluate the association of markers with aggressive PCa at diagnosis. The cohort comprised 41 patients with no cancer at biopsy, 48 patients with non-AG-PCa (Gleason score=6), and 65 patients with AG-PCa (Gleason score 7 or above). Targeted analyses of AG-PCa-associated glycoproteins previously identified in post-DRE urine samples were also applied to validate the post-DRE findings in non-DRE specimens. Data-independent acquisition mass spectrometry (DIA-MS) analysis was performed for glycosite-containing peptides. Fisher exact and Wilcoxon-Mann-Whitney tests were used for categorical and continuous variables respectively and logistic regression was evaluated using receiver operating characteristic (ROC) analysis for the urinary markers and marker panels. RESULTS: Urinary prostatic acid phosphatase (ACPP), CD97 antigen (CD97), and prostate-specific antigen (PSA) levels in pre-DRE specimens were associated with patients with AG-PCa compared to cancer-negative and non-AG-PCa. The analysis confirmed three of the previously reported post-DRE urinary glycoproteins and identified three new AG-PCa-associated glycoproteins including Fibrillin 1 (FBN1), Vitronectin (VTN) and Hemicentin 2 (HMCN2). A multi-marker panel composed of urinary PSA, VTN, HMCN2, CD97 achieved an AUC of 0.78 (p=2.69 × 10-9) for distinguishing AG-PCa from cancer-negative & Gleason 6. Analysis of differentially abundant glycopeptides in pre- and post-DRE samples showed that compared to glycopeptides from the post-DRE urine data, humoral immunity-related proteins were enriched in pre-DRE urine samples, whereas immune cell-related proteins were enriched in post-DRE urine samples. CONCLUSIONS: Comparisons between post-DRE and pre-DRE urine specimens for glycoproteins have shown that pre-DRE samples hold promise for a non-invasive and simple early option for AG-PCa detection in patients. The identified AG-PCa-associated glycoproteins may be further evaluated in large cohort of pre-DRE urine specimens for detecting clinically significant prostate cancer. Source of Funding: NCI/EDRN IAA No. ACN 17005-001-0000011 (Gregory Chesnut) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e545 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Indu Kohaar More articles by this author Yuefan Wang More articles by this author Tung-Shing Mamie Lih More articles by this author Naseruddin Höti More articles by this author Lori Sokoll More articles by this author Gregory Chesnut More articles by this author Gyorgy Petrovics More articles by this author Hui Zhang More articles by this author Expand All Advertisement PDF downloadLoading ...

Toxicity Study on the Effect of Ethanol Extracts of the Root and Leaf of Datura stramonium on the Brain and Non-Prostatic Acid Phosphatase Activity of Wistar rats

Abuse of psychoactive compounds is a growing global challenge, especially in countries with high unemployment rates. Toxicity study was conducted on the effect of ethanol extracts of the root and leaf of a regularly abused psychoactive plant in Nigeria (Datura stramonium) on the brain and non-prostatic acid phosphatase activity of Wistar rats using sixteen (16) Wistar rats of average weights 135g that were assigned into four (4) groups A, B, C and D with four (4) rats each. Groups A, B, and C were given the same concentration (3.5% in chilled Coca-Cola) of root extracts, leaf extracts, and both leaf and root extracts respectively while group D (control) was administered with equal volume of chilled Coca-Cola drink. The animals were kept in separate cages and fed with normal rat Chaw with water provided ad libitum. Rats in the treatment groups were given approximately 3.7mg/Kg body weight of the root extract, leaf extract, and both leaf and root extracts respectively while rats in the control group were given just a chilled Coca-Cola drink. All the animals were sacrificed after day 14th of administration. A qualitative phytochemical screening on the ethanol extracts of the root and leaf of D. stramonium plant showed that it contains alkaloids, tannins, saponins, flavonoids, and steroids. Histological examination of the brain of rats administered ethanol extracts of the root and leaf of the plant showed some levels of toxicity (exemplified by shrinkage of nerve cells) as well as increased activity of serum level of non prostatic acid phosphatase.

Electroacupuncture relieves neuropathic pain by inhibiting degradation of the ecto-nucleotidase PAP in the dorsal root ganglions of CCI mice.

Although electroacupuncture is widely used in chronic pain management, it is quite controversial due to its unclear mechanism. We hypothesised that EA alleviates pain by inhibiting degradation of the ecto-nucleotidase prostatic acid phosphatase (PAP) and facilitating ATP dephosphorylation in dorsal root ganglions (DRGs). We applied EA in male C57 mice subjected to chronic constriction injury (CCI) and assessed extracellular ATP and 5'-nucleotidease expression in DRGs. Specifically, we used a luminescence assay, quantitative reverse transcriptase-polymerase chain reaction, Western blotting, immunohistochemistry and nociceptive-related behavioural changes to gather data, and we tested for effects after PAP expression was inhibited with an adeno-associated virus (AAV). Moreover, membrane PAP degradation was investigated in cultured DRG neurons and the inhibitory effects of EA on this degradation were assessed using immunoprecipitation. EA treatment alleviated CCI surgery-induced mechanical pain hypersensitivity. Furthermore, extracellular ATP decreased significantly in both the DRGs and dorsal horn of EA-treated mice. PAP protein but not mRNA increased in L4-L5 DRGs, and inhibition of PAP expression via AAV microinjection reversed the analgesic effect of EA. Membrane PAP degradation occurred through a clathrin-mediated endocytosis pathway in cultured DRG neurons; EA treatment inhibited the phosphorylation of adaptor protein complex 2, which subsequently reduced the endocytosis of membrane PAP. EA treatment alleviated peripheral nerve injury-induced mechanical pain hypersensitivity in mice by inhibiting membrane PAP degradation via reduced endocytosis and subsequently promote ATP dephosphorylation in DRGs. In a mouse model of chronic pain, electroacupuncture treatment increased levels of prostatic acid phosphatase (PAP: an ecto-nucleotidase known to relieve pain hypersensitivity) by inhibiting PAP degradation in dorsal root ganglions. This promoted extracellular ATP dephosphorylation, inhibited glia activation and eventually alleviated peripheral nerve injury-induced mechanical pain hypersensitivity in mice. Our findings represent an important step forward in clarifying the mechanisms of pain relief afforded by acupuncture treatment.

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.

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.

A simple assay for direct colorimetric detection of prostatic acid phosphatase (PAP) at fg levels using biphosphonated loaded PEGylated gold nanoparticles

A fast and sensitive colorimetric assay for the determination of prostatic acid phosphatase (PAP) levels using biphosphonates-PEG-coated gold nanoparticles (BP-PEG-AuNPs) has been developed. Addition of different amounts of PAP to the AuNPs results in a significant change of color, from a red-wine color to purple, and finally to blue. The PAP should bind onto the AuNPs surface and crosslink the AuNPs inducing their aggregation and as a consequence a color change of the solution from wine red to purple/blue. The color change was monitored by UV–vis spectrophotometry or with the naked eye. The ensuing concentration-dependent red-shift of surface plasmon resonance absorption allows the determination concentration within the fg range in 10 min. Importantly, the visual detection limit (1 ng/mL) allows the rapid differential diagnosis with naked eye or image analyzer. This demonstrates that the color modification observed with BP-PEG-AuNP is effectively due to an interaction between PAP and BP.

Variants in ACPP are associated with cerebrospinal fluid Prostatic Acid Phosphatase levels

BackgroundProstatic Acid Phosphatase (PAP) is an enzyme that is produced primarily in the prostate and functions as a cell growth regulator and potential tumor suppressor. Understanding the genetic regulation of this enzyme is important because PAP plays an important role in prostate cancer and is expressed in other tissues such as the brain.MethodsWe tested association between 5.8 M SNPs and PAP levels in cerebrospinal fluid across 543 individuals in two datasets using linear regression. We then performed meta-analyses using METAL =with a significance threshold of p < 5 × 10−8 and removed SNPs where the direction of the effect was different between the two datasets, identifying 289 candidate SNPs that affect PAP cerebrospinal fluid levels. We analyzed each of these SNPs individually and prioritized SNPs that had biologically meaningful functional annotations in wANNOVAR (e.g. non-synonymous, stop gain, 3’ UTR, etc.) or had a RegulomeDB score less than 3.ResultsThirteen SNPs met our criteria, suggesting they are candidate causal alleles that underlie ACPP regulation and expression.ConclusionsGiven PAP’s expression in the brain and its role as a cell-growth regulator and tumor suppressor, our results have important implications in brain health such as cancer and other brain diseases including neurodegenerative diseases (e.g., Alzheimer’s disease and Parkinson’s disease) and mental health (e.g., anxiety, depression, and schizophrenia).Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2787-y) contains supplementary material, which is available to authorized users.

Correlation of Peripheral Vein Tumour Marker Levels, Internal Iliac Vein Tumour Marker Levels and Radical Prostatectomy Specimens in Patients with Prostate Cancer and Borderline High Prostate-Specific Antigen: A Pilot Study.

To correlate prostate-specific antigen (PSA), free to total PSA percentage (fPSA%) and prostatic acid phosphatase (PAP) levels from peripheral and pelvic venous samples with prostatectomy specimens in patients with prostate adenocarcinoma and borderline elevation of PSA. In this prospective institutional review board approved study, 7 patients with biopsy proven prostate cancer had a venous sampling procedure prior to prostatectomy (mean 3.2 days, range 1-7). Venous samples were taken from a peripheral vein (PVS), the right internal iliac vein, a deep right internal iliac vein branch, left internal iliac vein and a deep left internal iliac vein branch. Venous sampling results were compared to tumour volume, laterality, stage and grade in prostatectomy surgical specimens. Mean PVS PSA was 4.29, range 2.3-6 ng/ml. PSA and PAP values in PVS did not differ significantly from internal iliac or deep internal iliac vein samples (p > 0.05). fPSA% was significantly higher in internal iliac (p = 0.004) and deep internal iliac (p = 0.003) vein samples compared to PVS. One of 7 patients had unilateral tumour only. This patient, with left-sided tumour, had a fPSA% of 6, 6, 6, 14 and 12 in his peripheral, right internal iliac, deep right internal iliac branch, left internal iliac and deep left internal iliac branch samples respectively. There were no adverse events. fPSA%, unlike total PSA or PAP, is significantly higher in pelvic vein compared to peripheral vein samples when prostate cancer is present. Larger studies including patients with higher PSA values are warranted to further investigate this counterintuitive finding.

Effects of E/Z isomers of lycopene on experimental prostatic hyperplasia in mice

AimLycopene is a member of the carotenoid family and has strong anti-oxidant properties. Lycopene occurs in tomato-based food products primarily as an all-E isomer (80–97%),but its Z-isomers accounts for 79 to 88% of total lycopene in benign or malignant prostate tissues, while the specific biological functions of Z-isomers are still not clarified at present. This study was to examine the bioactive potency of Z-isomers on benign prostatic hyperplasia (BPH) in mice and to make a comparison of effective inhibition between Z-isomers and all-E isomer. MethodMice were divided into the Saline group, Vehicle control group and testosterone propionate induced BPH mice group (BPH model group, vehicle BPH model group, lycopene treated (5mg/kg and 2.5mg/kg), Z-isomers (57%) treated, Z-isomers (86%) treated, finasteride treated). The drugs were orally administered once a day consecutively for 30days. The inhibitory effects on BPH of all-E lycopene and Z-isomers were evaluated by prostatic index, prostatic acid phosphatase (PAP), estradiol, testosterone and dihydrotestosterone (DHT) levels in serum and histopathology examination. ResultsCompared with the BPH model group, E/Z isomers exhibited significant differences in prostatic index, PAP, estradiol, testosterone and DHT levels in serum and similar histological aspects observed in the mice of the control group. The present research also shows that Z-isomers may be more potent inhibitors than all-E isomers in BPH treatment.

In vivo anti-androgenic, anti-estrogenic and antioxidant activities of the aqueous extract of Eremomastax speciosa

ObjectiveTo evaluate the in vivo anti-androgenic, antioxidant activity and anti-estrogenic activities of Eremomastax speciosa (E. speciosa) in order to find new method for fighting against chronic diseases such as cancer. MethodsEvaluations of antiandrogenic and antioxidant activities were carried out on male rate receiving simultaneous daily administration of testosterone and different doses of aqueous extract of E. speciosa, during a period of 10 d. The evaluation of antiestrogenic activity was carried out on mature ovariectomized female rats receiving simultaneous daily administration of estradiol and different doses of extract, for a week. Then reproductive organs were weighted, levels of prostatic acid phosphatase, superoxide dismutase and catalase as well as some hematologic parameters were measured. ResultsThe treatment significantly reduced (P<0.01) the weight of ventral prostate, penis, Cowper's gland and the level of serum prostatic acid phosphatase; while a significant decrease (P<0.01) of the catalase activity was observed. A significant increase (P<0.05) in the lymphocyte number and significant decrease of monocyte (P<0.05) were noticed. The uterine relative weight were significantly reduced (P<0.01). ConclusionsGenerally, these results denote the antiandrogenic, antiestrogenic and immunomodulatory potential of E. speciosa.

A single low dose of cadmium exposure induces benign prostate hyperplasia like condition in rat: A novel benign prostate hyperplasia rodent model.

Abnormal prostate growth is the most prevalent pathological sign in aged human males, as reflected by high incidence of benign prostate hyperplasia (BPH) and prostate cancer. In spite of the high prevalence, the etiology and pathophysiology of BPH is unclear due to the lack of any established rodent model for study. It has been demonstrated that the cadmium (Cd) mimics the activity of androgen or estrogen by interacting with the steroid hormone receptors in the prostate and elicits BPH, but the specific receptor which binds to Cd is still unknown. Our lab studies with BPH patients highlighted a strong co-relation between smokings with increased Cd content. Changes in the maximum urinary flow rate (Qmax) and prostatic acid phosphatase (PAP) level further supports that Cd can induce BPH like condition. Therefore, the present study was aimed to induce BPH like condition in rats by Cd administration. The dose of cadmium was standardized in an age- and time-dependent manner, which was further examined by prostate weight, histology, and PAP levels that elucidated the pathogenesis of BPH. Further to understand the molecular basis, steroid hormone receptor antagonist experiment was performed. Gene expression and immunohistochemistry data suggest that Cd induces hyperplasia like condition by activating the androgen receptor and estrogen receptor-α and suppresses the action of estrogen receptor-β. The experimental model used here is a cost effective, less time consuming and potentially valuable tool for investigating the respective functions of epithelial and stromal hormone receptors. The applicability of this model would be helpful in understanding the pathogenesis of BPH and its progression.

Prostate cancer derived prostatic acid phosphatase promotes an osteoblastic response in the bone microenvironment

Approximately 90 % of patients who die of prostate cancer (PCa) have bone metastases, often promoting osteoblastic lesions. We observed that 88 % of castration-resistant PCa (CRPC) bone metastases express prostatic acid phosphatase (PAP), a soluble secreted protein expressed by prostate epithelial cells in predominately osteoblastic (n = 18) or osteolytic (n = 15) lesions. Additionally, conditioned media (CM) of an osteoblastic PCa xenograft LuCaP 23.1 contained significant levels of PAP and promoted mineralization in mouse and human calvaria-derived cells (MC3T3-E1 and HCO). To demonstrate that PAP promotes mineralization, we stimulated MC3T3-E1 cells with PAP and observed increased mineralization, which could be blocked with the specific PAP inhibitor, phosphonic acid. Furthermore, the mineralization promoted by LuCaP 23.1 CM was also blocked by phosphonic acid, suggesting PAP is responsible for the mineralization promoting activity of LuCaP 23.1. In addition, gene expression arrays comparing osteoblastic to osteolytic CRPC (n = 14) identified betacellulin (BTC) as a gene upregulated during the osteoblastic response in osteoblasts during new bone formation. Moreover, BTC levels were increased in bone marrow stromal cells in response to LuCaP 23.1 CM in vitro. Because new bone formation does occur in osteoblastic and can occur in osteolytic CRPC bone metastases, we confirmed by immunohistochemistry (n = 36) that BTC was highly expressed in osteoblasts involved in new bone formation occurring in both osteoblastic and osteolytic sites. These studies suggest a role for PAP in promoting the osteoblastic reaction in CRPC bone metastases and identify BTC as a novel downstream protein expressed in osteoblasts during new bone formation.

Prostatic acid phosphatase in serum and semen of dogs

The incidence of prostatic malignancy has increased the use of tissue markers to detect cancer. Tissue specific antigens or differentiation antigens are found on the surface of normal cells. Clinically, these antigens are important to diagnose alterations in the tissues and for immunotherapy. The objective of the present study was to evaluate the prostatic acid phosphatase concentration in blood and seminal plasma of intact and healthy dogs at different ages. The evaluation was carried out by spectrophotometer, using a commercial kit. The prostatic acid phosphatase (PAP) levels did not differ according to the age and did not correlate with age or prostatic dimensions verified by ultrasonography. The PAP concentration values varied greatly within each group. However, more studies are necessary to evaluate the role of prostatic acid phosphatase in the canine prostate and its importance as a diagnostic test for prostate disorders.

Prostate Biomarkers with Reference to Body Mass Index and Duration of Prostate Cancer

This study was performed to assess prostate biomarkers with reference to body mass index and duration of prostate cancer. A hospital based retrospective study was undertaken using data retrieved from the register maintained in the Department of Biochemistry of Manipal Teaching Hospital, Pokhara, Nepal between 1st January, 2009 and 28th February, 2012. Biomarkers studied were prostate specific antigen (PSA), acid phosphatase (ACP) and prostatic acid phosphatase (PAP), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (γGT). Demographic data including age, duration of disease, body weight, height and body mass index (BMI) were also collected. Duration of disease was categorized into three groups: <1 year, 1-2 years and >2 years. Similarly, BMI (kg/m2) was categorized into three groups: <23 kg/m2, 23-25 kg/ m2 and >25 kg/m2. Descriptive statistics and testing of hypothesis were used for the analysis using EPI INFO and SPSS 16 software. Out of 57 prostate cancers, serum level of PSA, ACP and PAP were increased above the cut-off point in 50 (87.5%), 30 (52.63%) and 40 (70.18%) respectively. Serum levels of PSA, ACP and PAP significantly declined with the duration of disease after diagnosis. We observed significant and inverse relation between PSA and BMI. Similar non-signficiant tendencies were apparent for ACP and PAP. Decreasing levels of prostate biomarkers were found with the duration of prostate cancer and with increased BMI. Out of prostate biomarkers, PSA was found to be significantly decreased with the duration of disease and BMI.

Inhibition of the Experimental Induction of Benign Prostatic Hyperplasia: A Possible Role for Fluted Pumpkin (Telfairia occidentalis Hook f.) Seeds

Introduction: Pumpkins are thought to be useful in the management of benign prostatic hyperplasia (BPH). The ability of a 15% Telfairia occidentalis seeds incorporated diet to inhibit hormonal induction of BPH in rats was studied. Materials and Methods: Twenty male Wistar rats were divided into 4 equal groups – one test group and three control groups. The test group was placed on the test diet and was given subcutaneous injections of dihydrotestosterone (DHT) and estradiol valerate (ratio 10:1) every other day for 28 days. One control group, ‘no test diet’ (ND) group, received the hormones, but was placed on a normal diet. The other two control groups, ‘no hormone’ (NH) and ‘no hormone/test diet’ (NHD), received subcutaneous olive oil (vehicle) for the same duration and were placed on the test and normal diets, respectively. Markers of BPH and hormone profile were determined using standard methods. Results: The mean relative prostate weight (×10³) was reduced in the test group (3.6 ± 0.2) relative to the ND group (4.0 ± 0.4). The protein content (mg/tissue) of the rats’ prostates decreased significantly (p < 0.05) from 68.3 ± 2.7 in the ND group to 43.4 ± 3.9 in the test group. Serum prostatic acid phosphatase levels (U/l) decreased significantly (p < 0.05) from 4.8 ± 0.4 in the ND group to 4.0 ± 0.9 in the test group. Histological findings corroborate these data. The testosterone:estradiol ratio (×10³) was significantly (p < 0.05) increased from 7.1 ± 0.1 in the ND group to 8.4 ± 0.4 in the test group. Conclusion: The test diet inhibited the induction of BPH in rats and may act by increasing the testosterone:estradiol ratio.

Ameliorative effect of cabbage extract on cadmium-induced changes on hematology and biochemical parameters of albino rats

The effect of dietary supplement containing cabbage on cadmium – induced toxicity was studied in wistar rats. The effect of cadmium was investigated in 3 animals groups. Group A, rats were fed normal basal diet only. Group B rats were placed on normal basal, mixed with cadmium chloride (3 mg/kg body weight daily) while group C rats were fed with basal diet mixed with Cadmium chloride (3 mg/kg body weight) and 0.5 kg dry cabbage pellets daily. Rats were monitored for 28 days. At the end of the treatment, the animals were sacrificed using chloroform vapor. Oral rat LD50 for Cadmium Chloride, Anhydrous is 88 mg/kg. The effect of cadmium treatment alone and combined cadmium-cabbage treatment on lipid peroxidation, as measured by malondialdehyde levels in testes and kidney, serum activities of acid phosphatase (ACP) and prostatic acid phosphatase (PAP) and alkaline phosphatase (ALP) were investigated alongside testicular and kidney organ weight and assessment of some hematological indices. The result showed that cadmium induced a significant increase in both testicular and kidney malondialdeyhde (MDA); but dietary cabbage seem to have a beneficial effect on lipid peroxidation. Cadmium also induced a 75% increase in ACP, 98% in PAP and 22% increase in ALP, but cabbage supplementation tended to produce a reduction in the activities of these enzymes (p = 0.001). Result of organ weight analysis in Cd –exposed rats showed a decrease in testes and kidney weight. Comparatively rats whose diet contained cadmium with cabbage supplementation showed an increase in organ weight. Administration of combined treatments of cadmium and cabbage may provide beneficial effects against cadmium-induced changes on the testicular and kidney weight, malondialdeyhde, liver enzymes; alkaline phosphatase, acid phosphatase and prostatic acid phosphatase levels by reducing cadmium –associated oxidative stress. Key words: Cabbage, cadmium, toxicity, amelioration.

Abstract LB-375: Development of new compounds specifically targeting prostate cancer bone metastases

Abstract Introduction: Bone metastases are a major cause of morbidity for men with prostate cancer (PCa). Although PCa cells produce osteoblastic metastases, there is an initial and ongoing osteoclast (OC)-mediated osteolytic phase that is essential for PCa bone metastases. OC-mediated bone resorption is dependent upon OC secretion of bone acid phosphatase. PCa cells in bone secrete high levels of prostatic acid phosphatase (PAP) which differs from BAP in that PAP enzymatic activity is inhibited by tartrate and glyceric acid, whereas BAP is tartrate-resistant. Hypothesis: PAP secreted by human PCa cells in bone acts similarly to OC-derived bone acid phosphatase to degrade bone matrix and enhance PCa bone-targeting and growth in bone. We developed new compounds consisting of glyceric acid or tartrate (known PAP inhibitors) conjugated to a bisphosphonate to inhibit PCa bone metastases. Methods: PCa bone metastases derived from 7 patients were immunostained for androgen receptor (AR), prostate specific antigen (PSA) and PAP expression. The VCaP human PCa cell line derived from a vertebral metastases was inoculated intratibially into SCID mice (n=8) and bone lesions immunostained for AR, PSA, and PAP. Co-cultures of MC3T3 osteoblasts and VCaP cells were treated with tartrate and the effects on cell number, PAP and bone alkaline phosphatase (ALP) secretion measured by ELISA. Glyceric Acid and Tartaric acid were then conjugated with alendronate and the effects of these new conjugates on PAP enzymatic activity were compared to alendronate alone and tartrate alone. Results: Human PCa bone lesions (7/7) had strongly positive expression of PAP, with little AR or PSA expression. 8/8 SCID mice inoculated with VCaP cells intratibially developed osteoblastic VCaP lesions and these similarly had high PAP expression and no PSA expression. Tartrate addition to co-cultures of VCaP and MC3T3 osteoblasts reduced MC3T3 cell numbers and ALP secretion. In vitro testing of the conjugates revealed that the glyceric acid-alendronate conjugate inhibited PAP enzymatic activity but the tartrate-alendronate conjugate and alendronate alone had no significant inhibitory activity. Discussion: We have evidence that PAP secretion by PCa cells enhances their bone metastatic ability. We have developed new bone-targeting agents that consist of alendronate conjugated to PAP-inhibitory small molecules for further development as oral agents to prevent and treat PCa bone metastases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-375.

Protein complexes/aggregates as potential cancer biomarkers revealed by a nanoparticle aggregation immunoassay

Protein–protein interactions and protein complex/aggregate formation play an essential role in almost all biological functions and activities. Through a nanoparticle aggregation immunoassay, we discovered that some proteins are substantially more complexed/aggregated in cancer tissues than normal tissues. This study examined four biomarkers proteins, CA125, CEA (carcinoembryonic antigen), CA19-9 and PAP (prostatic acid phosphatase) in ovarian, colon and prostate tissue lysates. The most exciting results were observed from the PAP assay of prostate tissues: prostate cancer can be clearly distinguished from normal prostate and prostate with benign conditions such as BPH (benign prostate hyperplasia) based on the complex/aggregation level of PAP in prostate tissue lysates. The complex/aggregate level of a protein can be potential biomarkers for cancer detection and diagnosis.