Combined tests of prostate specific antigen and testosterone will improve diagnosis and monitoring the progression of prostate cancer

Prostate-specific antigen (PSA) testing has been widely used to screen men for prostate cancer (PCa) and to monitor PCa progression. However, more studies have shown that around 15% of men with low or normal PSA levels have PCa. In this study, we aimed to investigate the relationship of androgen and PSA levels and to better understand the reason that some PCa patients have low serum PSA values. The in vitro data demonstrated that cultured LNCaP cells ceased to produce PSA after androgen withdrawal and resumed PSA production after androgen was re-added. The in vivo experiment results showed that 48% of PCa xenografts carrying mice have serum PSA level lower than 4 ng ml⁻¹. The serum PSA levels increased significantly with rises in testosterone (T) levels 1 week after T pellet implantation. These data indicated that the androgen is a key factor controlling the production of PSA. Low serum PSA levels in mice with PCa xenografts are associated with low serum T levels. Raising serum T levels in tumor caring mice will also significantly increase serum PSA level. This may have clinical implications when screening PSA in men, who have occult PCa.     

The influence of prostate volume on cancer detection in the Chinese population

In western populations, prostate volume （PV） has been proven to be one of the strongest predictors of detecting prostate cancer （PCa） in biopsies. We performed this study in a biopsy cohort, to evaluate associations among the prostate volume, prostate-specific antigen （PSA） and PCa detection in the Chinese population. Between the years, 2007-13, 1486 men underwent prostate biopsy at Huashan Hospital, Fudan University, Shanghai, China. The study population was divided into two groups for analysis according to total PSA （tPSA） range （4 ng m1-1 〈tPSA 〈20 ng m1-1 and tPSA 〉20 ng ml-1）. PV, age, tPSA, digital rectal examination （DRE） and transrectal ultrasound （TRUS） results were also included in the analysis. Although the positive biopsy rates decreased in both tPSA range groups, the downtrend was more pronounced in the 4 ng ml-2 〈tPSA 〈20 ng m1-1 group; therefore, we focused on 853 men in this group with increasing PV. In multivariate logistic regression analysis, only DRE was found to be associated with PCa in four PV groups （P 〈 0.05） and tPSA did not show a good predictive ability when PV exceeded 50 ml （P 〉 0.05）. Further, it may suggest that with increasing PV, the cancer detection rate decreased in men with different tPSA, DRE and TRUS nodule statuses （all P values for trends were 〈0.001）. Our study indicates that in tPSA ranging from 4 to 20 ng ml-1, the use of PV ranges of 0-35 ml, 35-50 ml and 〉50 ml might be taken into consideration for the biopsy decision-making in the Chinese population.     

PSA density improves the rate of prostate cancer detection in Chinese men with a PSA between 2.5–10.0 ng ml-1 and 10.1–20.0 ng ml-1: a multicenter study

Chinese men should have a higher prostate-specific antigen (PSA) “gray zone” than the traditional value of 2.5–10.0 ng ml⁻¹ since the incidence of prostate cancer (PCa) in Chinese men is relative low. We hypothesized that PSA density (PSAD) could improve the rate of PCa detection in Chinese men with a PSA higher than the traditional PSA “gray zone.” A total of 461 men with a PSA between 2.5 and 20.0 ng ml⁻¹, who had undergone prostatic biopsy at two Chinese centers were included in the analysis. The men were then further divided into groups with a PSA between 2.5–10.0 ng ml⁻¹ and 10.1–20.0 ng ml⁻¹. Receiver operating characteristic (ROC) curve was used to evaluate the efficacy of PSA and PSAD for the diagnosis of PCa. In men with a PSA of 2.5–10.0 ng ml⁻¹ or 10.1–20.0 ng ml⁻¹, the areas under the ROC curve were higher for PSAD than for PSA. This was consistent across both centers and the cohort overall. When the entire cohort was considered, the optimal PSAD cut-off for predicting PCa in men with a PSA of 2.5–10.0 ng ml⁻¹ was 0.15 ng ml⁻¹ ml⁻¹, with a sensitivity of 64.4% and specificity of 64.6%. The optimal cut-off for PSAD in men with a PSA of 10.1–20.0 ng ml⁻¹ was 0.33 ng ml⁻¹ ml⁻¹, with a sensitivity of 60.3% and specificity of 82.7%. PSAD can improve the effectiveness for PCa detection in Chinese men with a PSA of 2.5–10.0 ng ml⁻¹ (traditional Western PSA “gray zone”) and 10.1–20.0 ng ml⁻¹ (Chinese PSA “gray zone”).     

Two mutations identified in the androgen receptor of the new human prostate cancer cell line MDA PCa 2a

PURPOSE: We have characterized the androgen receptor (AR) in a new human prostate cancer cell line, MDA PCa 2a, that has recently been established from a bone metastasis of a patient whose cancer exhibited androgen-independent growth. MATERIALS AND METHODS: Androgen responsiveness of these cells was assessed by measuring the effect of DHT and R1881 on cell growth and PSA secretion. Scatchard analysis was used to characterize the affinity and abundance of AR protein. Using a PCR based strategy, genomic DNA of the entire coding region of AR gene was sequenced to identify possible mutations. RESULTS: These cells express abundant AR (Nmax = 685 +/- 149 fmol./mg. protein), but the AR binding affinity (Kd) for DHT is only 25 nM, approximately 50-fold lower affinity than the mutated AR in LNCaP prostate cancer cells (Kd = 0.5 nM) or the wildtype AR in MCF-7 breast cancer cells (Kd = 0.4 nM). Two mutations, L701H and T877A, were identified in the ligand binding domain of the AR gene. Compared with LNCaP cells, the new cell line is significantly less responsive to DHT and R1881 as well as to other androgens such as testosterone, androstenedione, and DHEA. Similar to LNCaP cells, the ligand specificity of the AR in MDA PCa 2a cells appears to be relaxed and non-androgens such as progesterone and estradiol act as agonists although with less potency than in LNCaP cells. Interestingly, in the absence of androgens, the new cell line expresses 15-fold higher baseline levels of PSA than LNCaP. CONCLUSIONS: Two mutations were identified in the AR gene of the MDA PCa 2a cell line that are likely responsible for the decreased androgen sensitivity and altered ligand specificity observed in these cells. Thus, this new cell line with partial androgen responsiveness and PSA expression can serve as a functionally relevant model system of bone metastatic prostate cancer, and can be used to investigate the role of AR mutations in prostate cancer and its progression to androgen independence.     

The differential effects of prostate stromal cells derived from different zones on prostate cancer epithelial cells under the action of sex hormones

It is well known that prostate cancer (PCa) occurs predominantly in the peripheral zone (PZ), whereas benign prostatic hyperplasia (BPH) typically develops in the transition zone. To identify possible mechanisms underlying zonal differences, we compared the effects of prostate stromal cells derived from the peripheral zone (PZsc) and the transition zone (TZsc) on a PCa epithelial cell line (PC3) in the presence of sex hormones. First, we observed that androgen receptor (AR) mRNA was more highly expressed in PZsc than TZsc when the cells were treated with dihydrotestosterone (DHT) and β-oestradiol (E2) (P<0.05). By ELISA, we looked for differences in the secretion of peptide growth factors from PZsc and TZsc. We found that keratinocyte growth factor (KGF) secretion increased with increasing concentrations of DHT (P<0.01) and was higher in PZsc than TZsc. Under treatment with DHT plus E2, PZsc secreted more transforming growth factor-β1 (TGF-β1) than TZsc, but this pattern was reversed when the cells were treated with E2 only. With increasing concentrations of DHT, insulin-like growth factor-1 (IGF-1) secretion increased in PZsc but decreased in TZsc. To further characterize the effects of PZsc and TZsc on PC3 cells, we developed a coculture model and performed MTT assays, Western blot analysis and real-time RT-PCR. We found that PZsc promoted PC3 cell proliferation and progression better than TZsc, particularly when treated with 10 nmol l⁻¹ DHT plus 10 nmol l⁻¹ E2. In conclusion, our data suggest that PZsc may have a greater capacity to induce PCa development and progression than TZsc via growth factors regulated by sex hormones. These findings provide possible mechanisms underlying zonal differences in prostate diseases, which may aid the search for novel therapeutic targets for PCa.     

Prostate volume as an independent predictor of prostate cancer in men with PSA of 10–50?ng ml?1

Prostate volume (PV) has been shown to be associated with prostate cancer (PCa) detection rates in men with a prostate-specific antigen (PSA) in the ‘grey zone'' (2.0–10.0 ng ml⁻¹). However, the PSA ‘grey zone'' in Asian men should be higher because the incidence of PCa in Asian men is relatively low. Therefore, we evaluated the association between PV and PCa detection rates in men with PSAs measuring 10–50 ng ml⁻¹. Men who underwent a 13-core prostatic biopsy with PV documentation participated in the study. A multivariate stepwise regression was used to evaluate whether the PV at time of prostate biopsy could predict the risk of PCa. The rates of PCa among men in different PSA ranges, stratified by PV medians (<60 and ≥60 ml), were calculated. There were 261 men included in the final analysis. PV was the strongest predictor of PCa risk (odds ratio, 0.02; P<0.001) compared to other variables. The PCa rates in men with PVs measuring <60 and ≥60 ml in the 10–19.9 ng ml⁻¹ PSA group were 40.6% and 15.1%, respectively, while the rates for men with PSAs measuring 20–50 ng ml⁻¹ were 65.1% and 26.8%. PV is an independent predictor of PCa in men with PSA measuring 10–50 ng ml⁻¹. In clinical practice, particularly for those countries with lower incidences of PCa, PV should be considered when counselling patients with PSAs measuring 10–50 ng ml⁻¹ regarding their PCa risks.     

Decreasing trend in prostate cancer with high serum prostate-specific antigen levels detected at first prostate-specific antigen-based population screening in Japan

To clarify the recent trends in prostate-specific antigen （PSA） distribution in men in Japan, we analyzed the PSA distributions of men undergoing PSA-based population screening. We summarized the annual individual data of PSA-based population screening in Kanazawa, Japan, from 2000 to 2011, and analyzed baseline serum PSA values of the participants at the first population screening. Serum PSA distributions were estimated in all participants and those excluding prostate cancer patients according to age. From 2000 to 2011, 19 620 men participated aged 54-69 years old in this screening program. Mean baseline serum PSA level of all participants at the first screening was 2.64 ng m1-1 in 2000, and gradually decreased to approximately 1.30 ng ml-I in 2006. That of participants excluding prostate cancer patients was 1.46 ng m1-1 in 2000, and there was no remarkable change during the study period. The 95t＂ percentiles in the participants excluding prostate cancer patients detected at the first population screening of men aged 54-59, 60-64, and 65-69 years old were 2.90, 3.60, and 4.50 ng m1-1, respectively. After the commencement of population screening, the proportion of prostate cancer patients with high serum PSA levels decreased. However, there were no changes in serum PSA levels in men without prostate cancer. Age-specific PSA reference level of men without prostate cancer in Japan was similar to that in China and Korea.     

Percent free prostate-specific antigen is effective to predict prostate biopsy outcome in Chinese men with prostate-specific antigen between 10.1 and 20.0 ng ml?1

Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0–10.0 ng ml⁻¹, however, it remains controversial whether %fPSA is effective in PSA range of 10.1–20.0 ng ml⁻¹ in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer (PCa) and high-grade PCa (HGPCa) was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA>4.0 ng ml⁻¹ or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA (%fPSA + PSA) was determined by the area under the receivers operating characteristic curve (AUC). %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0–10.0 ng ml⁻¹ and 10.1–20.0 ng ml⁻¹, respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0–10.0 ng ml⁻¹ and 10.1–20.0 ng ml⁻¹.     

A new potential risk factor in patients with erectile dysfunction and premature ejaculation： folate deficiency

We investigated serum folic acid （FA） levels in patients with erectile dysfunction （ED） and/or premature ejaculation （PE）. Fasting serum samples were obtained from 42 patients with ED, 36 with PE, 25 ED patients with PE, and 30 healthy men; the mean intravaginal ejaculation latency time （IELT） was measured during a 4 weeks baseline period. Levels of sex hormones （follicle-stimulating hormone, luteinizing hormone, total testosterone）, homocysteine （Hcys）, and FA were measured using chemiluminescent immunoassays. The sexual functions of PE patients and normal control men were evaluated using the Chinese Index of Premature Ejaculation （CIPE）. The abridged Intemational Index of Erectile Function-5 （IIEF-5） questionnaire was used to gauge erectile quality for ED patients and for normal controls. Serum FA concentrations were lower in ED （7.61 ~ 3.97 ng ml-1）, PE （9.37 ＋ 3.40 ng ml-1）, and ED/PE （8.84 ＋ 4.28 ng m1-1） patients than in healthy men （12.23 ~ 5.76 ng ml-z, P〈 0.05）. No significant differences in sex hormone levels were found between patients with sexual dysfunction and healthy controls （P 〉 0.05）. There were positive correlations between serum FA concentrations and ClPE scores （r= 0.530, P〈 0.01）, IIEF-5 scores （r= 0.589, P〈 0.01）, and IELT （r= 0.445, P〈 0.01）; negative correlations with Hcys concentrations （r= -0.487, P〈 0.01） were found in all participants. These findings showed a strong relationship between serum FA levels and sexual dysfunction, possibly due to an effect of FA on the metabolism of nitric oxide, Hcys, and 5-hydroxytryptamine.     

Control of LNCaP proliferation and differentiation: Actions and interactions of androgens,Iα,25-dihydroxycholecalciferol,all-trans retinoic acid, 9-cis retinoic acid,and phenylacetate

There is increasing evidence that growth and differentiation of prostatic carcinoma cells may be modulated not only by androgens and growth factors but also by vitamin D, retinoids, and phenylacetate (PA). The latter agonists may have a role in the prevention and therapy of prostate cancer but their exact therapeutic potential remains unclear. Since both retinoids and vitamin D act via nuclear receptors, the same way androgens do, we studied the interactions of these compounds with androgen-induced proliferation and differentiation using LNCaP cells as a model of androgen-responsive tumor cells. PA was included because of its suspected different mode of action. [³H]-thymidine incorporation was used as a measure of proliferative activity, secretion of prostate-specific antigen (PSA) as a measure of differentiated function. The present data show that 1α,25-dihydroxycholecalciferol (VD₃), all-trans retinoic acid (atRA), 9-cis retinoic acid (9cRA), and PA stimulated LNCaP cell-differentiated function in the presence or absence of androgens. The effects on cell growth were more complicated. In the absence of androgens growth stimulatory effects were observed for the retinoids and under some conditions for VD₃. These effects were limited, however, and tended to be more pronounced at low cell densities. In the presence of androgens nearly exclusively growth inhibitory effects were observed. On a molar basis VD₃ was the most effective antiproliferative agonist (ED₅₀ = 10⁻⁹ M). It completely neutralized the stimulatory effects of androgens. Growth inhibition was not due to a decrease in the concentration of androgen receptor: whereas atRA, atRA, 9cRA, and PA did not alter androgen receptor levels, VD₃ provoked a twofold increase. Neither in the presence nor in the absence of androgens did we observe any cooperativity in the growth stimulatory or inhibitory effects of VD₃ atRA, or 9cRA. To test whether treatment with any of the studied agonists resulted in a phenotypic reversion and sustained growth arrest, LNCaP cells were pretreated with VD₃, atRA, 9cRA, or PA for 6–12 days and reseeded at equal densities as untreated cells. In all cases tested [³H]-thymidine incorporation was restored within 6 days suggesting that none of these compounds caused irreversible growth inhibition. © 1996 John Wiley-Liss, Inc.     

The novel Ras antagonist, farnesylthiosalicylate, suppresses growth of prostate cancer in vitro

BACKGROUND: The majority of men with advanced prostate cancer (PCa) respond to androgen deprivation therapy (ADT) with objective evidence of tumor regression. However, these tumors will regrow in the presence of low-androgen levels after 12-18 months. Regrowth after ADT is associated with upregulation of growth factor (GF) mediated pathways. The compound farnesylthiosalicylate (FTS), a specific antagonist of the 21 kDa Ras protein, suppresses GF signaling and it might be a useful therapy against advanced PCa. METHODS: We measured androgen and GF dependent growth of androgen dependent LNCaP and androgen hypersensitive CWR-R1 PCa cells in response to specific inhibitors of GF pathways, including FTS. Inhibition of GF mediated signaling and cell-cycle pathways was confirmed by Western blotting of extracts from treated cells. RESULTS: Both LNCaP and CWR-R1 cells were dependent on GF signaling pathways for cell growth. FTS, as well as suppressing cell growth, inhibited GF signaling pathway activity and reduced the levels of E2F1, p-Rb, and p-cdc2, all GF dependent mediators of cell-cycle progression. CONCLUSIONS: These data suggest that FTS might be a useful agent against PCa that has relapsed after ADT.     

Androgen receptor-mediated growth and epidermal growth factor receptor induction in the human prostate cell line LNCaP

Human prostate tumor cells, LNCaP, contain androgen receptors and respond to androgens with increased growth rate. Although other steroid hormone receptors are not detectable in LNCaP cells, progesterone and estradiol stimulate the growth of these cells. The androgen receptor shows considerable cross binding activity with progesterone and estradiol but not with the glucocorticoid triamcinolone acetonide. The latter steroid does not have any effect on cell proliferation. LNCaP cells respond to epidermal growth factor (EGF) with an increased growth rate. Steroids that stimulate LNCaP cell proliferation also increase the number of EGF receptors per cell. In conclusion, LNCaP cells are sensitive to EGF. Different steroids bind to the androgen receptor and stimulate the proliferation of human prostate tumor cells. This stimulation of growth is preceded by an increase in EGF receptor number per cell.     

Environmental mercury exposure,semen quality and reproductive hormones in Greenlandic Inuit and European men: a cross-sectional study

Several animal studies indicate that mercury is a male reproductive toxicant, but human studies are few and contradictory. We examined semen characteristics and serum levels of reproductive hormones in relation to environmental exposure to mercury. Blood and semen samples were collected from 529 male partners of pregnant women living in Greenland, Poland and Ukraine between May 2002 and February 2004. The median concentration of the total content of mercury in whole blood was 9.2 ng ml⁻¹ in Greenland (0.2–385.8 ng ml⁻¹), 1.0 ng ml⁻¹ in Poland (0.2–6.4 ng ml⁻¹) and 1.0 ng ml⁻¹ in Ukraine (0.2–4.9 ng ml⁻¹). We found a significantly positive association between the blood levels of mercury and serum concentration of inhibin B in men from Greenland (β=0.074, 95% confidence interval (CI)=0.021 to 0.126) and in an analysis including men from all three regions (β=0.067, 95% CI=0.024 to 0.110). The association may be due to beneficial effects of polyunsaturated fatty acids (PUFAs), which are contained in seafood and fish. No significant association (P>0.05) was found between blood concentrations of mercury and any of the other measured semen characteristics (semen volume, total sperm count, sperm concentration, morphology and motility) and reproductive hormones (free androgen index (FAI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone and LH×testosterone) in any region. In conclusion, the findings do not provide evidence that environmental mercury exposure in Greenlandic and European men with median whole blood concentration up to 10 ng ml⁻¹ has adverse effects on biomarkers of male reproductive health.     

Effects of Ginkgo biloba extracts with mirodenafil on the relaxation of corpus cavernosal smooth muscle and the potassium channel activity of corporal smooth muscle cells

In this study, we investigated the effects of a combination of Ginkgo biloba extracts (GBE) and phosphodiesterase type 5 (PDE-5) inhibitors on the muscular tone of the corpus cavernosum and potassium channel activity of corporal smooth muscle cells. Strips of corpus cavernosum from male New Zealand white rabbits were mounted in organ baths for isometric tension studies. After contraction with 1×10⁻⁵ mol l⁻¹ norepinephrine, GBE (0.01–1 mg ml⁻¹) and mirodenafil (0.01–100 nmol l⁻¹) were added together into the organ bath. In electrophysiological studies, whole-cell currents were recorded by the conventional patch-clamp technique in cultured smooth muscle cells of the human corpus cavernosum. The corpus cavernosum was relaxed in response to GBE in a dose-dependent manner (from 0.64%±8.35% at 0.01 mg ml⁻¹ to 52.28%±11.42% at 1 mg ml⁻¹). After pre-treatment with 0.03 mg ml⁻¹ of GBE, the relaxant effects of mirodenafil were increased at all concentrations. After tetraethylammonium (TEA) (1 mmol l⁻¹) administration, the increased effects were inhibited (P<0.01). Extracellular administration of GBE increased the whole-cell K⁺ outward currents in a dose-dependent fashion. The increase of the outward current was inhibited by 1 mmol l⁻¹ TEA. These results suggest that GBE could increase the relaxant potency of mirodenafil even at a minimally effective dose. The K⁺ flow through potassium channels might be one of the mechanisms involved in this synergistic relaxation.     

神经内分泌分化对前列腺癌细胞生长及雄激素受体表达影响的实验研究

目的探讨神经内分泌分化对前列腺癌细胞生长的作用及对雄激素受体表达的影响。方法建立神经内分泌分化的前列腺癌细胞模型PC3MNE和LNCaPNE;采用甲基噻唑基四唑(MTT)试验观察其调节前列腺癌细胞生长的作用[以吸光度值(A)表示];采用逆转录聚合酶链反应和Western杂交方法检测LNCaPNE对LNCaP细胞雄激素受体表达的影响。结果PC3MNE的培养上清液可促进PC3M细胞的生长(A值在培养24h为034±018与050±009,48h为038±016与057±009,72h为038±015与055±005,P均<005);在有雄激素时,LNCaPNE的培养上清液不促进LNCaP细胞的生长,对其雄激素受体的表达也没有显著影响;去除雄激素后,LNCaPNE的培养上清液可促进LNCaP细胞的生长,并能下调其雄激素受体的表达(P均<005)。结论在雄激素阻断后,神经内分泌分化的前列腺癌细胞能以旁分泌的方式支持其他前列腺癌细胞生长,降低其雄激素受体的表达。     

Testosterone level and mortality in elderly men with systolic chronic heart failure

Previous studies on the prognostic significance of serum levels of androgens in patients with chronic heart failure (CHF) have yielded conflicting results. The aim of this study was to examine the relationship between serum concentration of testosterone and mortality in men with systolic CHF. A total of 175 elderly men (age≥60 years) with CHF were recruited. Total testosterone (TT) and sex hormone-binding globulin (SHBG) were measured, and estimated free testosterone (eFT) was calculated. The median follow-up time was 3.46 years. Of these patients, 17 had a TT level below 8 nmol l⁻¹ (230 ng dl⁻¹), 27 had an eFT level below 0.225 nmol l⁻¹ (65 pg ml⁻¹) and 12 had both. Using the age-specific tenth percentiles of TT and eFT in healthy men in our laboratory as cutoff points, the prevalences of TT and eFT deficiency was 21.7% (38/175) and 27.4% (48/175), respectively. Both TT and eFT were inversely associated with left ventricular ejection fraction (LVEF) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) (all P<0.01). Kaplan–Meier curves for patients in low, medium and high tertiles according to TT and eFT level showed significantly different cumulative survival rate (both P<0.01 by log-rank test). However, after adjustment for clinical variables, there were no significant associations of either TT or eFT levels with survival time (OR=0.97, 95% CI: 0.84–1.12, P=0.28 and OR=0.92, 95% CI: 0.82–1.06, P=0.14, respectively). Our study showed that levels of TT and eFT are commonly decreased in elderly patients with systolic CHF and related to disease severity, but they are not independent predictors for mortality.     

A longitudinal study of PSA and its influential factors in a cohort of Chinese men with initial PSA levels less than 4?ng ml?1

To evaluate the longitudinal change in prostate-specific antigen (PSA) and the influence of initial PSA on the PSA change. We retrospectively analysed health examination data collected at Beijing Hospital from March 2007 to November 2011. Men with an initial PSA levels less than 4 ng ml⁻¹ and an annual PSA test for 5 years were enrolled into the study. The men were separated into four groups by the initial PSA level (0–0.99, 1–1.99, 2–2.99 and 3–3.99 ng ml⁻¹), and the difference in PSA change among the four groups was analysed. A total of 1330 men were enrolled into the study. The mean age, initial PSA and PSA velocity (PSAV) were 58.17±14.63 (range 24–91) years, 1.18±0.79 (range 0–4) ng ml⁻¹ and 0.04±0.25 (range −1.34–2.02) ng ml⁻¹ year⁻¹. Pearson''s correlation analysis showed no correlation between initial PSA and PSAV (r=−0.036, P=0.189). The PSAV of the 0–0.99, 1–1.99, 2–2.99 and 3–3.99 ng ml⁻¹ initial PSA groups was 0.03±0.11, 0.07±0.32, 0.03±0.34 and −0.01±0.43 ng ml⁻¹ year⁻¹, respectively (P=0.06). As the initial PSA increased, the percentage of having a PSAV over 0.75 ng ml⁻¹ year⁻¹ and a negative PSAV both significantly increased. Males with a baseline PSA of 0–0.99, 1–1.99, 2–2.99 and 3–3.99 ng ml⁻¹ had a 1.88%, 6.16%, 16.30% and 57.81% chance, respectively, that their PSA would increase above 4.0 ng ml⁻¹ over the following 4 years (P<0.0001). The PSAV has no correlation with the initial PSA level. However, as the initial PSA increases, the chance that males will have an abnormal PSA or PSAV in the future increases.     

Identification and characterization of PLZF as a prostatic androgen-responsive gene

BACKGROUND: Promyelocytic leukemia zinc finger protein (PLZF) was initially identified by virtue of its fusion with RARalpha as a result of a variant t(11;17) chromosomal translocation that occurs in a small subset of acute promyelocytic leukemia (APL) patients. PLZF has been reported to have pro-apoptotic and anti-proliferative activity both in vivo and in vitro. METHODS: Using a modified subtractive hybridization, we identified PLZF as an androgen-responsive gene in the rat ventral prostate. Northern blot and Western blot were used to characterize the regulation of PLZF by androgens in LNCaP cells. Stable transfections of PLZF in LNCaP cells were performed to assay the effect of PLZF overexpression on LNCaP cell proliferation. RESULTS: PLZF mRNA was transiently up-regulated by androgens in the regressed ventral prostate of castrated adult rat. PLZF was also up-regulated by androgens, at both mRNA and protein levels, in the androgen-responsive human prostate cancer cell line LNCaP. Androgen induction of PLZF mRNA was not inhibited by protein synthesis inhibitor cycloheximide but inhibited by androgen receptor antagonist bicalutamide, indicating that PLZF is a direct androgen-responsive gene. To study the functions of PLZF in androgen action, LNCaP sublines stably overexpressing PLZF were generated. PLZF overexpression inhibited LNCaP proliferation either in the presence or absence of androgen, which is consistent with the reported anti-proliferative activity of PLZF. CONCLUSIONS: The above observations indicate that PLZF is an androgen-responsive gene with anti-proliferative activity in prostate cancer cells.     

Association of 25-hydroxy-vitamin D levels with semen and hormonal parameters

Vitamin D levels have been linked to various health outcomes including reproductive disorders. The purpose of this study was to explore the association between serum vitamin D level (25-hydroxy-vitamin D, or 25OHD) and semen and hormonal parameters. This is a cross-sectional study that included 170 healthy men recruited for the study of spermatogenesis from the general population. Men completed general and reproductive health questionnaires, and donated blood and semen samples. The main measures were hormonal (total and free testosterone, sex hormone-binding globulin, estradiol, follicle-stimulating hormone and luteinizing hormone) and semen parameters, adjusted (n=147) for age, body mass index (BMI), season, alcohol intake and smoking, in relation to categories of vitamin D levels, determined a priori. The mean age of the study population was 29.0±8.5 years and mean BMI was 24.3±3.2 kg m⁻². The mean 25OHD was 34.1±15.06 ng ml⁻¹. BMI showed a negative association with 25OHD. Sperm concentration, sperm progressive motility, sperm morphology, and total progressively motile sperm count were lower in men with ‘25OHD≥50 ng ml⁻¹'' when compared to men with ‘20 ng ml⁻¹≤25OHD<50 ng ml⁻¹''. Total sperm count and total progressive motile sperm count were lower in men with ‘25OHD<20 ng ml⁻¹'' when compared to men with ‘20 ng ml⁻¹≤25OHD<50 ng ml⁻¹''. The adjusted means of various hormonal parameters did not show statistical difference in the different categories of 25OHD. In conclusion, serum vitamin D levels at high and low levels can be negatively associated with semen parameters.