Endocrine Disruptors and Estrogens in Human Prostatic Tissue.

Endocrine disruptors (EDs) are ubiquitous substances both in the environment and everyday products that interfere with the hormonal system. Growing evidence demonstrates their adverse effects on the organism, including the reproductive system and the prostate, owing to their (anti)estrogenic or antiandrogenic effects. Since EDs can interact with steroid hormone actions on-site, understanding the levels of intraprostatic EDs in conjunction with steroids may hold particular significance. The aim of this study was to develop and validate a method for determining estrogens, various groups of EDs (bisphenols, parabens, oxybenzone and nonylphenol) and phytoestrogens in their unconjugated and conjugated forms in prostate tissue by liquid chromatography-tandem mass spectrometry, and subsequently analyze 20 human prostate tissue samples. The method enabled 20 compounds to be analyzed: estrogens (estrone, estradiol, estriol), bisphenols (bisphenol A- BPA, BPS, BPF, BPAF, BPAP, BPZ, BPP), parabens (methyl-, ethyl-, propyl-, butyl-, benzyl- paraben), oxybenzone, nonylphenol and phytoestrogens (daidzein, genistein, equol) with LLOQs between 0.017-2.86 pg/mg of tissue. The most frequently detected EDs in prostate tissues were propylparaben (conjugated and unconjugated forms in 100 % of tissues), methylparaben (unconjugated in 45 % and conjugated in 100 %), ethylparaben (unconjugated in 25 % and conjugated in 100 % BPA (unconjugated in 35 % and conjugated in 60 % and oxybenzone (both forms in 45 % To the best of our knowledge, this is the first study detecting EDs, phytoestrogens and estriol conjugate (E3C) in the prostate. E3C was the most abundant estrogen in prostatic tissue. This highlights the need for further explorations into estrogen metabolism within the prostate.

Evaluating Biochemically Recurrent Prostate Cancer: Histologic Validation of 18F-DCFPyL PET/CT with Comparison to Multiparametric MRI.

Background Prostate cancer recurrence is found in up to 40% of men with prior definitive (total prostatectomy or whole-prostate radiation) treatment. Prostate-specific membrane antigen PET agents such as 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) may improve detection of recurrence compared with multiparametric MRI; however, histopathologic validation is lacking. Purpose To determine the sensitivity, specificity, and positive predictive value (PPV) of 18F-DCFPyL PET/CT based on histologic analysis and to compare with pelvic multiparametric MRI in men with biochemically recurrent prostate cancer. Materials and Methods Men were prospectively recruited after prostatectomy and/or radiation therapy with rising prostate-specific antigen level (median, 2.27 ng/mL; range, 0.2-27.45 ng/mL) and a negative result at conventional imaging (bone scan and/or CT). Participants underwent 18F-DCFPyL PET/CT imaging and 3.0-T pelvic multiparametric MRI. Statistical analysis included Wald and modified χ2 tests. Results A total of 323 lesions were visualized in 77 men by using 18F-DCFPyL or multiparametric MRI, with imaging detection concordance of 25% (82 of 323) when including all lesions in the MRI field of view and 53% (52 of 99) when only assessing prostate bed lesions. 18F-DCFPyL depicted more pelvic lymph nodes than did MRI (128 vs 23 nodes). Histologic validation was obtained in 80 locations with sensitivity, specificity, and PPV of 69% (25 of 36; 95% confidence interval [CI]: 51%, 88%), 91% (40 of 44; 95% CI: 74%, 98%), and 86% (25 of 29; 95% CI: 73%, 97%) for 18F-DCFPyL and 69% (24 of 35; 95% CI: 50%, 86%), 74% (31 of 42; 95% CI: 42%, 89%), and 69% (24 of 35; 95% CI: 50%, 88%) for multiparametric MRI (P = .95, P = .14, and P = .07, respectively). In the prostate bed, sensitivity, specificity, and PPV were 57% (13 of 23; 95% CI: 32%, 81%), 86% (18 of 21; 95% CI: 73%, 100%), and 81% (13 of 16; 95% CI: 59%, 100%) for 18F-DCFPyL and 83% (19 of 23; 95% CI: 59%, 100%), 52% (11 of 21; 95% CI: 29%, 74%), and 66% (19 of 29; 95% CI: 44%, 86%) for multiparametric MRI (P = .19, P = .02, and P = .17, respectively). The addition of 18F-DCFPyL to multiparametric MRI improved PPV by 38% overall (P = .02) and by 30% (P = .09) in the prostate bed. Conclusion Findings with 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) were histologically validated and demonstrated high specificity and positive predictive value. In the pelvis, 18F-DCFPyL depicted more lymph nodes and improved positive predictive value and specificity when added to multiparametric MRI. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Zukotynski and Rowe in this issue.

Omega-3 Fatty Acids Survey in Men under Active Surveillance for Prostate Cancer: from Intake to Prostate Tissue Level.

Dietary omega-3 fatty acids (ω3), particularly long-chain ω3 (LCω3), have protective effects against prostate cancer (PCa) in experimental studies. Observational studies are conflicting, possibly because of the biomarker used. This study aimed at evaluating associations between grade reclassification and ω3 levels assessed in prostatic tissue, red blood cells (RBC), and diet. We conducted a validation cross-sectional study nested within a phase II clinical trial. We identified 157 men diagnosed with low-risk PCa who underwent a first active surveillance repeat prostate biopsy session. Fatty acid (FA) intake was assessed using a food frequency questionnaire and their levels measured in prostate tissue and RBC. Associations were evaluated using logistic regression. At first repeat biopsy session, 39 (25%) men had high-grade PCa (grade group ≥2). We found that high LCω3-eicosapentaenoic acid (EPA) level in prostate tissue (odds ratio (OR) 0.25; 95% (confidence interval (CI) 0.08-0.79; p-trend = 0.03) was associated with lower odds of high-grade PCa. Similar results were observed for LCω3 dietary intake (OR 0.30; 95% CI 0.11-0.83; p-trend = 0.02) but no association for RBC. LCω3-EPA levels in the target prostate tissue are inversely associated with high-grade PCa in men with low-risk PCa, supporting that prostate tissue FA, but not RBC FA, is a reliable biomarker of PCa risk.

Apiaceous Vegetables and Cruciferous Phytochemicals Reduced PhIP-DNA Adducts in Prostate but Not in Pancreas of Wistar Rats.

We previously showed rats fed with apiaceous vegetables, but not with their putative chemopreventive phytochemicals, reduced colonic DNA adducts formed by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a dietary procarcinogen. We report here the effects of feeding apiaceous and cruciferous vegetables versus their purified predominant phytochemicals, either alone or combined, on prostate and pancreatic PhIP-DNA adduct formation. In experiment I, male Wistar rats received three supplemented diets: CRU (cruciferous vegetables), API (apiaceous vegetables), and CRU+API (both types of vegetables). In experiment II, rats received three diets supplemented with phytochemicals matched to their levels in the vegetables from experiment I: P + I (phenethyl isothiocyanate and indole-3-carbinol), FC (furanocoumarins; 5-methoxypsoralen, 8-methoxypsoralen, and isopimpinellin), and COMBO (P + I and FC combined). After 6 days of feeding, PhIP was injected (10 mg/kg body weight) and animals were killed on day 7. PhIP-DNA adducts were analyzed by LC-MS/MS. In prostate, PhIP-DNA adducts were reduced by API (33%, P < .05), P + I (45%, P < .001), and COMBO (30%, P < .01). There were no effects observed in pancreas. Our results suggest that fresh vegetables and purified phytochemicals lower PhIP-DNA adducts and may influence cancer risk.

[The effect of drug oil moxibustion for contents of Zinc and C-reactive protein in succus prostaticus of chronic nonbacterial prostatitis].

OBJECTIVE: To observe the clinical effects differences and partial mechanism for chronic nonbacterial prostatitis (CNP) among drug oil moxibustion, simple moxibustion, and conventional western medicine. METHODS: A total of 120 patients who met the criteria of inclusion were randomly assigned into a drug oil moxibustion group, a moxibustion group and a western medication group, 40 cases in each one. Moxibustion was used at Guanyuan (CV 4), Zhongji (CV 3), Qihai (CV 6) and bilateral Yinlingquan (SP 9), Sanyinjiao (SP 6), Shenshu (BL 23), Mingmen (GV 4), Pangguangshu (BL 28), Ciliao (BL 32), and Zhibian (BL 54), etc. The same moxibustion was used at the same acupoints in the drug oil moxibustion group after external application of medicated oil. Thirty min treatment was used once a day in alternated abdomen and back. In the western medication group, oral tamsulosin hydrochloride capsules were applied once a day, one capsule at a time. All the treatment was given for 30 days. Chronic prostatitis symptom index from National Institutes for Health (NIH-CPSI), the contents of Zinc (Zn) and C-reactive protein (CRP), as well as the number of white blood cells (WBC) and density of lecithin bodies were observed before and after treatment and 1 month after treatment. The effects were evaluated after treatment. RESULTS: After treatment, the total effective rate of the drug oil moxibustion group was 90.0% (36/40), which was significantly higher than 72.5% (29/40) of the moxibustion group and 62.5% (25/40) of the western medication group (both P<0.05). After treatment and at follow-up in the three groups, the NIH-CPSI scores were lower than those before treatment (all P<0.05), and those in the drug oil moxibustion group were lower than the results in the moxibustion group and the western medication group (all P<0.05). The contents of Zn in the three groups were higher than those before treatment (all P<0.05), with better results in the drug oil moxibustion group (all P<0.05), and higher Zn contents in the moxibustion group compared with those in the western medication group (both P<0.05). The CRP levels were lower than those before treatment (all P<0.05), and those in the drug oil moxibustion group were better than those in the moxibustion group and western medication group (all P<0.05). The CRP contents in the moxibustion group were lower than those in the western medication group (both P<0.05). The number of WBC were lower than those before treatment (all P<0.05), with better results in the drug oil moxibustion group (all P<0.05). The concentrations of lecithin were higher than those before treatment (all P<0.05), with better results in the drug oil moxibustion group (all P<0.05). CONCLUSIONS: The clinical effect of drug oil moxibustion is better than those of simple moxibustion and western medicine, which has advantages in improving clinical symptoms, Zn, the density of lecithin body and decreasing CRP content and the number of WBC.

In vivo evaluation of hot water extract of Acorus gramineus root against benign prostatic hyperplasia.

BACKGROUND: Acorus gramineus has been reported to exhibit various pharmacological effects including inhibition of cholesterol synthesis, enhancement of lipid metabolism, prevention of dementia and inhibition of mast cell growth. According to the Chinese compendium of materia media, it has been reported that Acorus spp. is effective for sedation, dementia prevention as well as diuretic effect. In addition, it showed more than equivalent activity compared to furosoemide, a drug known to be effective in diuretic action in animal model study. However, their effectiveness against benign prostatic hyperplasia (BPH) of Acorus gramineus has not been reported. This study was designed to evaluate the effect of Acorus gramineus root hot water extract (AG) against BPH in vivo. METHODS: Male rats, 10 weeks of age and weighing 405 g ± 10 g, were used for this study. Biomarkers were evaluated including prostate weight, prostate weight ratio, hormonal changes, 5-α reductase type II androgen receptor (AR) of the prostate gland and anti-oxidant activation factors related to BPH. These biomarkers were measured in vivo test. RESULTS: AG showed significant effect at the 250 and 500 mg/kg/day in rats. Groups treated with AG displayed significantly lower levels of prostate gland weight (0.79 g) compared to the BPH induced group (1.19 g). Also, dihydrotestosterone (DHT) level was decreased from 61.8 to 100% and androgen receptor expression level was decreased from 111 to 658%. Any hematological toxicity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level wasn't observed. CONCLUSION: This study indicated that AG was effective for reducing BPH symptoms. TRIAL REGISTRATION: Not applicable.

PSA-PSMA profiles and their impact on sera PSA levels and angiogenic activity in hyperplasia and human prostate cancer.

AIM: The relevance of prostate specific antigen (PSA)-prostate specific membrane antigen (PSMA) profiles in pathologic prostate (hyperplasia and cancer) has not been fully understood. The aim of this study is to investigate the impact of PSA-PSMA profiles on sera PSA levels and angiogenic activity in benign prostate hyperplasia (BPH) and prostate carcinoma (PC). PATIENTS AND METHODS: The study has been carried out in 6 normal prostate (NP), 29 BPH and 33 PC with dominant Gleason grade>8. Immunohistochemical analysis has been performed. Monoclonal antibodies 3E6 and ER-PR8 have been used to assess PSMA and PSA expression respectively. The evaluation of angiogenesis has been made by CD34 immune marker. Serum levels of PSA have been assayed by Immulite autoanalyser. RESULTS: The study of each protein separately among sera PSA levels showed that PSMA expression and angiogenic activity have the highest intensity in PC patients with serum PSA levels>20 ng/mL. Nevertheless, the lowest tissue PSA expression was found in PC patients with this latter sera PSA group. The most relevant results showed that in PC patients (PSA+, PSMA+) and (PSA-, PSMA+) profile were found to be inversely related to sera PSA levels. In PC patients, a high immunoexpression of (PSA+, PSMA+) profile has detected in the sera PSA group>20 ng/mL; whereas a high immunoexpression of (PSA-, PSMA+) profile was detected in the sera PSA group between 0 and 4 ng/mL. The highest angiogenic activity was found in PC patients with (PSA+, PSMA+) profile. CONCLUSIONS: Our findings clearly have supported the feasibility of PSA-PSMA profiles to improve in vivo diagnostic and therapeutic approaches in prostate cancer patients.

Age-related histological and zinc content changes in adult nonhyperplastic prostate glands.

To clarify age-related histological and Zn content changes in nonhyperplastic adult prostate glands, a quantitative morphometric and energy-dispersive X-ray fluorescence analyses were performed. The prostates were obtained from autopsies of 63 subjects aged 21-70 years who died mainly from trauma. It was found that histologically normal prostate tissue undergoes substantial changes throughout aging. These changes are reflected in an increase of the percent volume of the glandular lumen for the third to fifth decades, reaching a maximum for the decade 41-50 years. Over the same period, the percent volume of the stroma remains steady, but the percent volume of epithelium decreases, approximately, linearly with age. The percent volume of glandular lumen (reflects the volume of prostatic fluid) in the prostate gland of men aged 41 to 50 years is 1.5-fold higher than that in men aged 21 to 30 years, but the epithelium/lumen (prostatic fluid) ratio is approximately twofold lower. This suggests that accumulation of the prostatic fluid develops from 30 to 50 years of age. This accumulation of the prostatic fluid results in an increase of the Zn mass fraction in the prostate. In turn, when the intraprostatic Zn level exceeds a certain level by the end of the fifth decade, it begins to work as a trigger for different factors, all of which increase the proliferation of stromal cells. Deductions from these results allow possible partial explanations of both relevant prostatic aging mechanisms and the effects of dietary interventions using supplementary Zn.

Prostatic response to supranutritional selenium supplementation: comparison of the target tissue potency of selenomethionine vs. selenium-yeast on markers of prostatic homeostasis.

Prostate cancer is the product of dysregulated homeostasis within the aging prostate. Supplementation with selenium in the form of selenized yeast (Se-yeast) significantly reduced prostate cancer incidence in the Nutritional Prevention of Cancer Trial. Conversely, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed no such cancer-protective advantage using selenomethionine (SeMet). The possibility that SeMet and Se-yeast are not equipotent in promoting homeostasis and cancer risk reduction in the aging prostate has not been adequately investigated; no direct comparison has ever been reported in man or animals. Here, we analyzed data on prostatic responses to SeMet or Se-yeast from a controlled feeding trial of 49 elderly beagle dogs-the only non-human species to frequently develop prostate cancer during aging-randomized to one of five groups: control; low-dose SeMet, low-dose Se-yeast (3 µg/kg); high-dose SeMet, high-dose Se-yeast (6 µg/kg). After seven months of supplementation, we found no significant selenium form-dependent differences in toenail or intraprostatic selenium concentration. Next, we determined whether SeMet or Se-yeast acts with different potency on six markers of prostatic homeostasis that likely contribute to prostate cancer risk reduction-intraprostatic dihydrotestosterone (DHT), testosterone (T), DHT:T, and epithelial cell DNA damage, proliferation, and apoptosis. By analyzing dogs supplemented with SeMet or Se-yeast that achieved equivalent intraprostatic selenium concentration after supplementation, we showed no significant differences in potency of either selenium form on any of the six parameters over three different ranges of target tissue selenium concentration. Our findings, which represent the first direct comparison of SeMet and Se-yeast on a suite of readouts in the aging prostate that reflect flux through multiple gene networks, do not further support the notion that the null results of SELECT are attributable to differences in prostatic consequences achievable through daily supplementation with SeMet, rather than Se-yeast.

Is sampling transitional zone in patients who had prior negative prostate biopsy necessary?

OBJECTIVE: To assess the necessity of transitional zone sampling of the prostate during repeat prostate biopsy procedures. METHODS: Patients treated for lower urinary tract symptoms with transurethral resection of the prostate (TURP) from April 2004 to July 2009 whom had at least 1 negative prostate biopsy prior to this treatment were chosen as the study group. A histopathological analysis of surgical specimens was employed to determine cancer detection rates. RESULTS: A total of 72 patients with the mean age of 66.1, mean prostate-specific antigen (PSA) of 10.4 ng/mL and mean prostate volume of 63.2 cc were included. Of the patients, 50 had 1 biopsy set, 17 had 2 sets, 4 had 3 sets and 1 patient had 4 sets of consecutive biopsies. All biopsy results were negative for prostate cancer. After the analysis of surgical specimens obtained during TURP, cancer was detected in 3 patients (4.2%). Transitional zone sampling during prostate biopsies did not significantly improve the cancer detection rate. Transitional zone sampling was performed in 29 biopsies taken from 20 patients, one of whom (5%) had prostate cancer. The remaining 71 biopsies were taken from 52 patients without transitional zone sampling, and cancer was detected in 2 (3.8%) of them. CONCLUSIONS: Since no significant difference was observed between patient groups (those with and those without transitional zone biopsies) in the detection of prostate cancer in the transitional zone, strategies for increasing the number of cores taken from transitional zone during repeat biopsies should be reconsidered.

The effect of age on 12 chemical element contents in the intact prostate of adult men investigated by inductively coupled plasma atomic emission spectrometry.

The effect of age on 12 chemical element contents in intact prostate of 64 apparently healthy, 13-60-year-old men (mean age 36.5 years) was investigated by inductively coupled plasma atomic emission spectrometry. Mean values (M ± SΕΜ) for mass fraction (milligrams/kilogram, on dry weight basis) of Ba, Ca, Cu, Fe, K, Mg, Na, P, S, Sr, and Zn were: Ba 1.18 ± 0.12, Ca 2,178 ± 160, Cu 10.7 ± 0.9, Fe 122 ± 5, K 12,530 ± 360, Mg 1,100 ± 70, Na 10,470 ± 320, P 7,580 ± 300, S 8,720 ± 180, Sr 1.85 ± 0.28, and Zn 782 ± 97, respectively. The upper limit of mean content of V was ≤0.22 mg/kg. A tendency of age-related increase in Ca, Fe, Na, and Zn mass fraction as well an increase in Zn/Ba, Zn/Ca, Zn/Cu, Zn/Fe, Zn/K, Zn/Mg, Zn/Na, Zn/P, Zn/S, and Zn/Sr ratios in prostate was observed. A significant positive correlation was seen between the prostatic zinc and Ca, Cu, Fe, Mg, Na, and P contents.

Prostatic alpha-linolenic acid (ALA) is positively associated with aggressive prostate cancer: a relationship which may depend on genetic variation in ALA metabolism.

Previous observational studies have reported associations between prostate cancer and alpha-linolenic acid (ALA). However, few investigations have been able to study this relationship prospectively and in well-controlled settings. Moreover, no studies have determined whether single nucleotide polymorphisms (SNPs) that influence ALA metabolism are associated with this common cancer. The purpose of this study was to explore associations between prostatic levels of ALA, SNPs and prostate cancer-specific biomarkers in samples collected from a previous randomized clinical trial conducted using a presurgical model and which tested the effects of flaxseed supplementation, a rich source of ALA, prior to prostatectomy (n = 134). Serum prostate-specific antigen (PSA) was determined and immunohistochemistry was used to assess tumor proliferation rate (Ki67). Prostatic ALA was determined with gas chromatography. Seven previously identified SNPs associated with delta-6 desaturase activity (rs99780, rs174537, rs174545, rs174572, rs498793, rs3834458 and rs968567) were tested for associations with prostatic ALA, PSA and Ki67. Despite consuming seven times more ALA per day, men in the flaxseed arm had similar amounts of prostatic ALA relative to men not consuming flaxseed. In unadjusted analysis, there were significant positive associations between prostatic ALA and PSA (ρ = 0.191, p = 0.028) and Ki67 (ρ = 0.186, p = 0.037). After adjusting for covariates (flaxseed, age, race, BMI and statin-use) the association between ALA and PSA remained (p = 0.004) but was slightly attenuated for Ki67 (p = 0.051). We did not observe associations between any of the SNPs studied and prostatic ALA; however, in models for PSA there was a significant interaction between rs498793 and ALA and for Ki67 there were significant interactions with ALA and rs99780 and rs174545. Independent and inverse associations were observed between rs174572 and Ki67. This study provides evidence that prostatic ALA, independent of the amount of ALA consumed, is positively associated with biomarkers of aggressive prostate cancer and that genetic variation may modify this relationship.

Solitary fibrous tumor of the prostate: a report of two cases.

We here report two cases of solitary fibrous tumor (SFT) arising in the prostate. Two men, 66 and 69 years old, with urinary tract symptoms were diagnosed with SFT on transrectal needle biopsy and transurethral resection of the prostate, respectively. The tumors were removed by a low anterior resection including tumor, prostate and rectum en bloc and cystoprostatectomy, respectively. Both tumors were well-circumscribed but also showed some infiltration of the prostate glands. They were composed of storiform bundles of bland spindle cells that stained strongly for CD34 and vimentin but negative for muscle markers. Although rare, SFT should be considered as differential diagnosis of spindle cell lesions on prostate biopsies.

Transforming growth factor ß-receptor II protein expression in benign prostatic hyperplasia is associated with prostate volume and inflammation.

OBJECTIVE: To assess transforming growth factor ß-receptor II (TGFBRII) protein expression in benign prostatic hyperplasia (BPH) using immunohistochemistry analysis, and to compare the analysis with phenotypic properties. METHODS: TGFBRII protein expression was profiled using three clinical outcome tissue microarrays (TMAs), sampled from 231 patients who underwent surgery for BPH. Using these TMAs, five inflammatory cell markers were also assessed, including CD3, CD4, CD8, CD20, and CD163. The surgical procedure was open prostatectomy in 95 patients and transurethral resection of the prostate in 136 patients. RESULTS: TGFBRII protein expression was found in BPH epithelium cells for both basal and secretory cells, as well as in fibromuscular stromal cells. TGFBRII staining was also strong in most of the lymphocytes infiltrating the prostate. TGFBRII stromal staining was found to be significantly associated with prostate volume (P = 0.04), whereas TGFBRII epithelial staining was found to be significantly associated with 5-α-reductase-inhibitor medical therapy received by patients before surgery (P = 0.004). Both stromal and epithelial TGFBRII staining were found to be associated with CD4 T-lymphocyte infiltrate, independently of prostate volume (P < 0.001 and P = 0.002). CONCLUSIONS: TGFBRII protein expression in BPH is associated with prostate gland volume and with CD4 T-lymphocyte prostatitis. TGFBRII might be a promising therapeutic target to prevent prostate enlargement or even to decrease prostate volume.

Selenium and cadmium levels and ratios in prostates, livers, and kidneys of nonsmokers and smokers.

Cadmium (Cd) from cigarette smoke, environmental, and nutritional sources accumulates in the human prostate where it interacts with selenium (Se) in a manner suggesting the formation of a 1:1 Cd-Se-protein complex. At low Cd exposures and adequate Se status, this interaction may be beneficial as it results in the detoxification of Cd. At higher exposures, Cd may weaken or abolish the anticarcinogenic effects of Se and increase prostate cancer risk. In some older men and especially in smokers, Cd levels in prostates reach levels in stoichiometric excess over Se, which may be the reason why heavy smokers are at higher risk of developing lethal forms of prostate cancer. In the liver and the kidneys, Cd accumulates as well, but in these organs, Cd is efficiently sequestered through metallothionein formation. In the prostate, this mode of detoxification is not available or less efficient, causing Cd to interact with Se and to increase prostate cancer risk.

Zinc transporter expression profiles in the rat prostate following alterations in dietary zinc.

Zinc plays important roles in numerous cellular activities and physiological functions. Intracellular zinc levels are strictly maintained by zinc homeostatic mechanisms. Zinc concentrations in the prostate are the highest of all soft tissues and could be important for prostate health. However, the mechanisms by which the prostate maintains high zinc levels are still unclear. In addition, the response of the prostate to alterations in dietary zinc is unknown. The current study explored cellular zinc levels and zinc transporter expression profiles in the lobes of the prostate during dietary marginal zinc depletion. Rats were given either zinc-adequate (ZA, 30 mg Zn/kg) or marginal zinc-deficient (MZD, 5 mg Zn/kg) diet for 9 weeks. In addition, a subgroup of the MZD rats was supplemented with phytase (1,500 unit/kg diet) to improve zinc bioavailability. We found that both zinc concentrations and ZnT2 expression in the prostate dorsolateral lobes were substantially higher than in the ventral lobes (P < 0.05). Marginal zinc depletion significantly decreased ZnT2 expression in the dorsolateral lobes (P < 0.05), and phytase supplementation had a trend to increase ZnT2 expression. In addition, of all measured zinc transporters, only ZnT2 mRNA abundance was significantly correlated to the zinc concentrations in the dorsolateral lobe. No correlations were found between zinc transporter expression and zinc concentrations in the ventral lobes. These results indicate that ZnT2 may play a significant role in the maintenance of zinc homeostasis in the prostate.

Effects of flaxseed dietary supplementation on sperm quality and on lipid composition of sperm subfractions and prostatic granules in rabbit.

Lipids are the main structural/functional components of the sperm, and their composition may undergo a series of modifications in relation to either physiologic events (capacitation and acrosome reaction) and/or diet. The goals of the current study were (1) to investigate whether a flaxseed (FS) dietary supplementation could affect the lipid and fatty acid profile of sperm subfractions and of prostatic granules (PGs) and (2) to evaluate the effects of dietary FS on rabbit buck semen quality. Accordingly, 20 adult New Zealand White rabbits were fed ad libitum a control diet (CO) or a diet supplemented with 5% extruded FS. Integration of diet with FS, as a consequence of the linolenic acid (C18:3n-3; LNA; 56%), increased the dietary n-3/n-6 ratio and resulted in a substantial rearrangement of sperm fatty acid composition at the subcellular level, mainly of polyunsaturated fatty acid (PUFA)n-3 (8.3% vs. 14.3%, P<0.05). The lipid and fatty acid profiles of sperm tail membrane were the most affected, undergoing the following significant changes: (1) a reduction by half of linoleic acid (C18:2n-6; LA) and docosapentaenoic acid (22:5n-6; DPA), and a reduction of cholesterol (-70%); (2) a concomitant increase of LNA (+65%), docosahexaenoic acid (22:6n-3; DHA; +83%), and of oleic acid (C18:1n-9, +61%). As a consequence, the sperm of FS-fed rabbits had a twice higher n-3/n-6 ratio and phospholipid/cholesterol ratio compared with the control sperm. These changes might have been on the basis of the higher responsiveness to hypo-osmotic solution and, hence, the higher sperm track speed observed for the FS group. Also, the membrane integrity and viability of the LNA-enriched sperm were both improved. On the other hand, the presence of lignans in FS might have accounted for the reduction of sperm cholesterol in the semen of FS-treated rabbits. The responsiveness of sperm to acrosome reaction was not affected by the dietary treatment probably due to supranutritional level of vitamin E and to the higher number of PGs, which are known to play a key role in sperm capacitation. In conclusion, our data showed for the first time that the integration of FS into the rabbit diet may improve sperm quality by modifying the sperm lipid composition and that the sperm subfractions and the PGs respond differently to the FS-induced lipid manipulation.

Disturbed homeostasis of zinc and other essential elements in the prostate gland dependent on the character of pathological lesions.

Pathophysiological changes in the prostate take the form of benign prostate hyperplasia (BPH) and prostate adenocarcinoma (PCa). In prostate, zinc is particularly important to its normal functioning, especially in terms of the consequences of hormone disturbance. The aim of this study was to assess the levels of Zn, Cu, Ca, Mg, and Se in the prostate dependent on the character of patological changes. Zinc, copper, magnesium and calcium were determined by AAS and selenium with spectrofluorometric method. Zn levels in BPH patients were over twofold higher than in controls. On the other hand, in the patients with PCa, the levels of Zn were found almost three times lower than in BPH patients and by almost 50% lower than in controls. In this study, significant changes in the levels of other essential elements were observed. The results apparently confirm the disturbed homeostasis of zinc and other essential elements in the etiology of BPH and PCa.

Age-related changes of the concentrations of select elements in the prostates of Japanese.

To elucidate compositional changes of the prostate with aging, the authors investigated age-related changes of elements in the prostates and the relationships among their elements using Japanese and Thai. After ordinary dissections by students at Nara Medical University and Chiang Mai University were finished, the prostates were resected from the subjects. Fifty-seven Japanese subjects ranged in age from 65 to 101 years (average age = 82.5 +/- 7.8 years), whereas 13 Thai subjects ranged in age from 43 to 86 years (average age = 67.9 +/- 11.9 years). After ashing with nitric acid and perchloric acid, element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that although there were no significant correlations between age and seven element contents, such as Ca, P, S, Mg, Zn, Fe, and Na, in the prostates of Japanese, high contents of Ca (>5 mg/g) and P (>4 mg/g) were contained in one fourth of the prostates of Japanese over 70 years of age. In the prostates of Thai, a significant direct correlation was found between age and Ca content, but it was not found between age and the other element contents, such as P, S, Mg, Zn, Fe, and Na. Regarding the relationships among their elements, extremely significant direct correlations were found among the contents of Ca, P, Mg, Zn, and Na in the prostates of Japanese. In the prostates of Thai, significant direct correlations were found among the contents of Ca, Mg, and Zn, but no significant correlations were found between Ca and P contents and between P and Mg contents. Regarding the relationships among their elements, there were differences between the prostates of Japanese and Thai. To examine whether element contents changed in prostatic hypertrophy, the transverse width of the Japanese prostates was measured. No significant correlations were found between the transverse width and element contents, such as Ca, P, S, Mg, Zn, Fe, and Na, in the Japanese prostates. Therefore, it is unlikely that the increase of elements results in prostatic hypertrophy.

Reduced growth and integrin expression of prostate cells cultured with lycopene, vitamin E and fish oil in vitro.

Integrins are transmembrane proteins that facilitate the interaction of cells with the extracellular environment. They have also been implicated in cancer progression. The effects of nutrients thought to be involved in the prevention of prostate cancer on integrin expression have not been determined. Prostate cancer cell lines representing a range of malignancy from normal (RWPE-1) to highly invasive phenotypes (22Rv1 < LNCaP < PC-3) were cultured with or without lycopene (10 nM), vitamin E (5 microm) or fish oil (100 microm) for 48 h. Growth and integrin (alpha2beta1, alphavbeta3 and alphavbeta5) expression were assessed using Trypan Blue exclusion and monoclonal antibodies combined with flow cytometry. Vitamin E enhanced (P < 0.001) whereas fish oil reduced the growth of all the cell lines tested (P < 0.001). Lycopene had no effect on growth. All the malignant cell lines exhibited lower expression of alpha2beta1 with the addition of lycopene to culture media. Supplemental fish oil reduced alpha2beta1 in most invasive cell lines (LNCaP and PC-3). Each nutrient at physiological levels reduced integrins alphavbeta3 and alphavbeta5 in most invasive cell lines (PC-3). The results suggest that integrins may represent an additional target of bioactive nutrients and that the effects of nutrients may be dependent on the type of cell line used.