Ethnobiology and Ethnopharmacology of Lepidium meyenii (Maca), a Plant from the Peruvian Highlands

PubMed Central

Gonzales, Gustavo F.

2012-01-01

Lepidium meyenii (maca) is a Peruvian plant of the Brassicaceae family cultivated for more than 2000 years, which grows exclusively in the central Andes between 4000 and 4500 m altitude. Maca is used as a food supplement and also for its medicinal properties described traditionally. Since the 90s of the XX century, an increasing interest in products from maca has been observed in many parts of the world. In the last decade, exportation of maca from Peru has increased from 1,415,000 USD in 2001 to USD 6,170,000 USD in 2010. Experimental scientific evidence showed that maca has nutritional, energizer, and fertility-enhancer properties, and it acts on sexual dysfunctions, osteoporosis, benign prostatic hyperplasia, memory and learning, and protects skin against ultraviolet radiation. Clinical trials showed efficacy of maca on sexual dysfunctions as well as increasing sperm count and motility. Maca is a plant with great potential as an adaptogen and appears to be promising as a nutraceutical in the prevention of several diseases. PMID:21977053

Ethnobiology and Ethnopharmacology of Lepidium meyenii (Maca), a Plant from the Peruvian Highlands.

PubMed

Gonzales, Gustavo F

2012-01-01

Lepidium meyenii (maca) is a Peruvian plant of the Brassicaceae family cultivated for more than 2000 years, which grows exclusively in the central Andes between 4000 and 4500 m altitude. Maca is used as a food supplement and also for its medicinal properties described traditionally. Since the 90s of the XX century, an increasing interest in products from maca has been observed in many parts of the world. In the last decade, exportation of maca from Peru has increased from 1,415,000 USD in 2001 to USD 6,170,000 USD in 2010. Experimental scientific evidence showed that maca has nutritional, energizer, and fertility-enhancer properties, and it acts on sexual dysfunctions, osteoporosis, benign prostatic hyperplasia, memory and learning, and protects skin against ultraviolet radiation. Clinical trials showed efficacy of maca on sexual dysfunctions as well as increasing sperm count and motility. Maca is a plant with great potential as an adaptogen and appears to be promising as a nutraceutical in the prevention of several diseases.

Effect of short-term and long-term treatments with three ecotypes of Lepidium meyenii (MACA) on spermatogenesis in rats.

PubMed

Gonzales, Carla; Rubio, Julio; Gasco, Manuel; Nieto, Jessica; Yucra, Sandra; Gonzales, Gustavo F

2006-02-20

Lepidium meyenii (Brassicaceae), known as Maca, is a Peruvian hypocotyl that grows exclusively between 4000 and 4500 m above sea level in the central Andes. Maca is traditionally employed in the Andean region for its supposed fertility-enhancing properties. The study aimed to test the hypothesis that different ecotypes of Maca (Red, Yellow and Black) after short-term (7 days) and long-term (42 days) treatment affects differentially spermatogenesis adult rats. After 7 days of treatment with Yellow and Red Maca, the length of stage VIII was increased (P<0.05), whereas with Black Maca stages II-VI and VIII were increased (P<0.05). Daily sperm production (DSP) was increased in the group treated with Black Maca compared with control values (P<0.05). Red or Yellow Maca did not alter DSP and epididymal sperm motility was not affected by treatment with any ecotype of Maca. After 42 days of treatment, Black Maca was the only ecotype that enhanced DSP (P<0.05). Moreover, Black Maca was the only that increased epididymal sperm motility (P<0.05). In relation to the control group, Red Maca did not affect testicular and epididymal weight nor epididymal sperm motility and sperm count; however, prostate weight was reduced (P<0.05). Black or Yellow Maca did not affect prostate weight. In conclusion, there were differences in the biological response of the three ecotypes of Maca (Yellow, Red and Black). Black Maca appeared to have more beneficial effect on sperm counts and epididymal sperm motility.

Trametes meyenii possesses elevated dye degradation abilities under normal nutritional conditions compared to other white rot fungi

PubMed Central

2014-01-01

Several species of white-rot fungi were investigated for their utility in prolonged decolouration of the recalcitrant sulfonated azo dye, amaranth. Trametes pubescens, T. multicolor, T. meyenii and T. versicolor decoloured amaranth azo-dye best on low-nitrogen agar-solidified media whereas Bjerkandera adusta and Phlebia radiata were most effective in low nitrogen medium supplemented with manganese. Trametes cotonea did not decolour effectively under any condition. The decolouring Trametes species were also effective in liquid culture whereas B. adusta and P. radiata were not. Trametes meyenii, T. pubescens and T. multicolor were equal to or better than commonly employed T. versicolor at decolouring amaranth. This is the first study to show the dye decolouration potential of T. meyenii, T. pubescens, and T. multicolor. Supplementing with Mn(II) increased assayable manganese peroxidase activity, but not long-term decolouration, indicating that laccase is the main decolourizing enzyme in these Trametes species. This appears to be because of inadequate Mn3+ chelation required by manganese peroxidase because adding relatively low amounts of malonate enhanced decolouration rates. The ability of Trametes meyenii to simultaneously decolour dye over prolonged periods of time while growing in relatively nutrient-rich medium appears to be unique amongst white-rot fungi, indicating its potential in wastewater bioremediation. PMID:25401075

Extraction, purification and antioxidant activities of the polysaccharides from maca (Lepidium meyenii).

PubMed

Zha, Shenghua; Zhao, Qingsheng; Chen, Jinjin; Wang, Liwei; Zhang, Guifeng; Zhang, Hong; Zhao, Bing

2014-10-13

Water-soluble polysaccharides were separated from maca (Lepidium meyenii) aqueous extract (MAE). The crude polysaccharides were deproteinized by Sevag method. During the preparation process of maca polysaccharides, amylase and glucoamylase effectively removed starch in maca polysaccharides. Four Lepidium meyenii polysaccharides (LMPs) were obtained by changing the concentration of ethanol in the process of polysaccharide precipitation. All of the LMPs were composed of rhamnose, arabinose, glucose and galactose. Antioxidant activity tests revealed that LMP-60 showed good capability of scavenging hydroxyl free radical and superoxide radical at 2.0mg/mL, the scavenging rate was 52.9% and 85.8%, respectively. Therefore, the results showed that maca polysaccharides had a high antioxidant activity and could be explored as the source of bioactive compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neuroprotective effects of Lepidium meyenii (Maca).

PubMed

Pino-Figueroa, Alejandro; Nguyen, Diane; Maher, Timothy J

2010-06-01

The neuroprotective activity of the plant Lepidium meyenii (Maca) was studied in two experimental models: in vitro and in vivo. Crayfish neurons were pretreated with vehicle or the pentane extract from Maca, subjected to H(2)O(2), and their viability determined microscopically and chemically. A significant concentration-neuroprotective effect relationship was demonstrated. The pentane extract was then administered intravenously to rats prior to and following middle cerebral artery occlusion. While infarct volumes were decreased for the lower dose, higher doses increased infarct volumes compared to controls. These results suggest a potential application of Maca as a neuroprotectant.

Peruvian Maca: Two Scientific Names Lepidium Meyenii Walpers and Lepidium Peruvianum Chacon – Are They Phytochemically-Synonymous?

PubMed Central

Meissner, Henry O.; Mscisz, Alina; Kedzia, Bogdan; Pisulewski, Pawel; Piatkowska, Ewa

2015-01-01

Using Liquid Chromatography-Mass Spectrometry (LCMS) , profiles of the two isotypes labelled under the same common name Maca deposited in the Medicinal Plant Herbarium, in Australia and Poland, but identified under two different scientific names Lepidium meyenii Walpers (L. meyenii) and Lepidium peruvianum Chacon (L. peruvianum) are presented. The two isotypes correspond to two holotypes of Peruvian medicinal herb known under the same common name “Maca”, as originally deposited in the Herbarium of San Marcos University in Lima, Peru dated back to 1843 and 1990 respectively. The results demonstrate distinct differences in taxonomy, visual appearance, phytochemical profiles and DNA sequences of the two researched Maca isotypes, suggesting that the two Maca specimens are dissimilar and formal use of the term “synonymous” to L. meyenii and L. peruvianum may be misleading. On the basis of presented results the scientific name L. meyenii, used since 1843 up-today for cultivated Peruvian Maca by numerous reference sources worldwide, including Regulatory Bodies in the USA, EU, Australia and most lately in China, appears to be used in error and should be formally revised. It is concluded, that the isotype of cultivated Peruvian Maca labelled under its scientific name Lepidium peruvianum Chacon, provides all the characteristics peculiar to this historically-documented herb grown in Andean highlands, which may be linked to its traditional use and accepted functionality, confirmed in recent clinical study to be relevant to its present day use for expected dietary, therapeutic and health benefits.

In silico profiling for secondary metabolites from Lepidium meyenii (maca) by the pharmacophore and ligand-shape-based joint approach.

PubMed

Yi, Fan; Tan, Xiao-Lei; Yan, Xin; Liu, Hai-Bo

2016-01-01

Lepidium meyenii Walpers (maca) is an herb known as a traditional nutritional supplement and widely used in Peru, North America, and Europe to enhance human fertility and treat osteoporosis. The secondary metabolites of maca, namely, maca alkaloids, macaenes, and macamides, are bioactive compounds, but their targets are undefined. The pharmacophore-based PharmaDB targets database screening joint the ligand shape similarity-based WEGA validation approach is proposed to predict the targets of these unique constituents and was performed using Discovery Studio 4.5 and PharmaDB. A compounds-targets-diseases network was established using Cytoscape 3.2. These suitable targets and their genes were calculated and analyzed using ingenuity pathway analysis and GeneMANIA. Certain targets were identified in osteoporosis (8 targets), prostate cancer (9 targets), and kidney diseases (11 targets). This was the first study to identify the targets of these bioactive compounds in maca for cardiovascular diseases (29 targets). The compound with the most targets (46) was an amide alkaloid (MA-24). In silico target fishing identified maca's traditional effects on treatment and prevention of osteoporosis, prostate cancer, and kidney diseases, and its potential function of treating cardiovascular diseases, as the most important of this herb's possible activities.

Dutasteride reduces prostate size and prostate specific antigen in older hypogonadal men with benign prostatic hyperplasia undergoing testosterone replacement therapy.

PubMed

Page, Stephanie T; Hirano, Lianne; Gilchriest, Janet; Dighe, Manjiri; Amory, John K; Marck, Brett T; Matsumoto, Alvin M

2011-07-01

Benign prostatic hyperplasia and hypogonadism are common disorders in aging men. There is concern that androgen replacement in older men may increase prostate size and symptoms of benign prostatic hyperplasia. We examined whether combining dutasteride, which inhibits testosterone to dihydrotestosterone conversion, with testosterone treatment in older hypogonadal men with benign prostatic hyperplasia reduces androgenic stimulation of the prostate compared to testosterone alone. We conducted a double-blind, placebo controlled trial of 53 men 51 to 82 years old with symptomatic benign prostatic hyperplasia, prostate volume 30 cc or greater and serum total testosterone less than 280 ng/dl (less than 9.7 nmol/l). Subjects were randomized to daily transdermal 1% T gel plus oral placebo or dutasteride for 6 months. Testosterone dosing was adjusted to a serum testosterone of 500 to 1,000 ng/dl. The primary outcomes were prostate volume measured by magnetic resonance imaging, serum prostate specific antigen and androgen levels. A total of 46 subjects completed all procedures. Serum testosterone increased similarly into the mid-normal range in both groups. Serum dihydrotestosterone increased in the testosterone only but decreased in the testosterone plus dutasteride group. In the testosterone plus dutasteride group prostate volume and prostate specific antigen (mean ± SEM) decreased 12% ± 2.5% and 35% ± 5%, respectively, compared to the testosterone only group in which prostate volume and prostate specific antigen increased 7.5% ± 3.3% and 19% ± 7% (p = 0.03 and p = 0.008), respectively, after 6 months of treatment. Prostate symptom scores improved in both groups. Combined treatment with testosterone plus dutasteride reduces prostate volume and prostate specific antigen compared to testosterone only. Coadministration of a 5α-reductase inhibitor with testosterone appears to spare the prostate from androgenic stimulation during testosterone replacement in older

Phytochemical and biological assessments on Lipidium meyenii (maca) and Epimidium sagittatum (horny goat weed).

PubMed

Qureshi, Mahmood; Mehjabeen, -; Noorjahan, -; Muhammad, Shafi; Siddiqui, Faheem Ahmed; Baig, Iftikhar; Ahmad, Mansoor

2017-01-01

The effects of Lipidium meyenii (maca, LM) and Epimidium sagittatum (horny goat weed, ES) have been investigated due to their involvement in fertilization. Both of the drugs showed good results before, during and after fertilization in male and female mice. The results revealed that the crude extract of Lipidium meyenii caused a significant decrease in the no. of writhes at 300 and 500mg/kg (p<0.05) as compare to control, Epimidium sagittatum and standard drug. The gross behavioral, open field, exploratory behaviour, forced swimming test for stress, diuretic activity, chronic toxicity with the effect on reproduction of both male and female and change in body weight were also studied. The phytochemical study showed the presence of tannin, alkaloid, carbohydrate, rich protein and absence of sterol in LM, whereas ES shows presence of sterol and less protein. LS improve in muscle activity and exploratory behaviours without any toxic effects on mice and their pups. It does not have diuretic effect for first two hour but act normally after initial phase of drug therapy. Epimidium sagittatum has dual action that is at low dose it has slight stimulation action and at high dose little depressive effect. ES also has some diuretic effect. Overall these results suggest that LM is highly effective remedy for treatment of impotency and reduces stress and depression, because of dual effect ES not only suggested as an anxiolytic medicine but also effective in female hormonal disorder.

Lepidium meyenii (Maca) does not exert direct androgenic activities.

PubMed

Bogani, P; Simonini, F; Iriti, M; Rossoni, M; Faoro, F; Poletti, A; Visioli, F

2006-04-06

Maca is the edible root of the Peruvian plant Lepidum meyenii, traditionally employed for its purported aphrodisiac and fertility-enhancing properties. This study aimed at testing the hypothesis that Maca contains testosterone-like compounds, able to bind the human androgen receptor and promote transcription pathways regulated by steroid hormone signaling. Maca extracts (obtained with different solvents: methanol, ethanol, hexane and chloroform) are not able to regulate GRE (glucocorticoid response element) activation. Further experiments are needed to assess which compound, of the several Maca's components, is responsible of the observed in vivo effects.

Statin Use, Serum Lipids, and Prostate Inflammation in Men with a Negative Prostate Biopsy: Results from the REDUCE Trial.

PubMed

Allott, Emma H; Howard, Lauren E; Vidal, Adriana C; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freedland, Stephen J

2017-06-01

Statin use is associated with lower advanced prostate cancer risk. In addition to cholesterol lowering, statins have systemic anti-inflammatory properties. However, their effect on histologic prostate inflammation is not well understood, particularly among men at increased prostate cancer risk but with a negative prostate biopsy. We examined associations between serum lipid levels, statin use, and histologic prostate inflammation using data from 6,655 men with a negative baseline prostate biopsy in the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial. Statin use and lipid levels [total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides] were assessed at baseline. Inflammation was assessed by central review. Logistic regression was used to examine the effects of lipids and statin use on presence and extent of chronic and acute prostate inflammation [none, moderate (<20%), severe (≥20% biopsy cores)]. Chronic and acute inflammation affected 77% and 15% of men, respectively. Men with high HDL (≥60 vs. <40 mg/dL) had reduced presence of acute inflammation [OR, 0.79; 95% confidence interval (CI), 0.63-0.99] and were less likely to have severe acute inflammation (OR, 0.66; 95% CI, 0.45-0.97), but there were no other associations between lipids and inflammation. Statin users had reduced presence of chronic inflammation (OR, 0.81; 95% CI, 0.69-0.95) and were less likely to have severe chronic (OR, 0.80; 95% CI, 0.68-0.95) and severe acute inflammation (OR, 0.73; 95% CI, 0.53-1.00), relative to non-users. Given the possible role for inflammation in prostate cancer, the inverse association between statins and prostate inflammation suggests a mechanism linking statins with lower advanced prostate cancer risk. Cancer Prev Res; 10(6); 319-26. ©2017 AACR . ©2017 American Association for Cancer Research.

Effect of gamma irradiation on phenol content, antioxidant activity and biological activity of black maca and red maca extracts (Lepidium meyenii walp).

PubMed

Zevallos-Concha, A; Nuñez, D; Gasco, M; Vasquez, C; Quispe, M; Gonzales, G F

2016-01-01

This study was performed to determine the effects of gamma irradiation on UV spectrum on maca, total content of polyphenols, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activities and in vivo biological activities of red and black maca extracts (Lepidium meyenii). Adult mice of the strain Swiss aged 3 months and weighing 30-35 g in average were used to determine biological activities. Daily sperm production, effect on testosterone-induced prostate hyperplasia and forced swimming test were used to determine the effect of irradiation on biological activities of maca extracts. Irradiation did not show differences in UV spectrum but improves the amount of total polyphenols in red maca as well as in black maca extracts. In both cases, black maca extract has more content of polyphenols than red maca extract (p < 0.01). Gamma irradiation significantly increased the antioxidant capacity (p < 0.05). No difference was observed in daily sperm production when irradiated and nonirradiated maca extract were administered to mice (p > 0.05). Black maca extract but not red maca extract has more swimming endurance capacity in the forced swimming test. Irradiation of black maca extract increased the swimming time to exhaustion (p < 0.05). This is not observed with red maca extract (p > 0.05). Testosterone enanthate (TE) increased significantly the ventral prostate weight. Administration of red maca extract in animals treated with TE prevented the increase in prostate weight. Irradiation did not modify effect of red maca extract on prostate weight (p > 0.05). In conclusion, irradiation does not alter the biological activities of both black maca and red maca extracts. It prevents the presence of microorganisms in the extracts of black or red maca, but the biological activities were maintained.

Effects of different varieties of Maca (Lepidium meyenii) on bone structure in ovariectomized rats.

PubMed

Gonzales, Carla; Cárdenas-Valencia, Isaias; Leiva-Revilla, Johanna; Anza-Ramirez, Cecilia; Rubio, Julio; Gonzales, Gustavo F

2010-01-01

This study was designed to determine the effect of different varieties of maca (Lepidium meyenii) on bone structure in ovariectomized (OVX) rats. 36 female rats were randomly divided into 6 groups: sham and OVX rats treated with vehicle, estradiol (40 microg/kg), black, yellow or red maca (63 mg/ml) for 4 weeks. At the end of the treatment, uterine weight, femoral bone and lumbar vertebra histomorphology were assessed. Ovariectomy reduced weight, diameter and width of the femoral bone. Estradiol, black and red maca treatment reduced the effect of ovariectomy on these variables. Histological analyses revealed that estradiol, black and red maca treatments reversed the effect of ovariectomy by increasing the trabecular bone area in the second lumbar vertebra. Uterine weight was reduced in OVX rats, and estradiol but neither black nor red maca increased uterine weight. Red and black maca have protective effects on bone architecture in OVX rats without showing estrogenic effects on uterine weight. 2010 S. Karger AG, Basel.

Elevated insulin and reduced insulin like growth factor binding protein-3/prostate specific antigen ratio with increase in prostate size in Benign Prostatic Hyperplasia.

PubMed

Sreenivasulu, Karli; Nandeesha, Hanumanthappa; Dorairajan, Lalgudi Narayanan; Rajappa, Medha; Vinayagam, Vickneshwaran

2017-06-01

Insulin and insulin like growth factor-1 (IGF-1) have growth promoting effects, while insulin like growth factor binding protein-3 (IGFBP-3) has growth inhibitory effects. The present study was designed to assess the concentrations of insulin, IGF-1, IGFBP-3 and their association with prostate size in patients with BPH. Ninety 90 BPH cases and 90 controls were enrolled in the study. Insulin, IGF-1, IGFBP-3, PSA, testosterone and estradiol were estimated in both the groups. Insulin, IGF-1 and estradiol were increased and IGFBP-3/PSA was decreased in BPH cases when compared with controls. Insulin (r=0.64, p=0.001) and IGF-1 (r=0.22, p=0.03) were positively correlated and IGFBP-3/PSA (r=-0.316, p=0.002) were negatively correlated with prostate size in BPH. Multivariate analysis showed that insulin (p=0.001) and IGFBP-3/PSA (p=0.004) predicts the prostate size in patients with BPH. Insulin was increased and IGFBP-3/PSA was reduced in BPH patients with increased prostate size. At a cutoff concentration of 527.52, IGFBP-3/PSA ratio was found to differentiate benign growth of prostate from normal prostate with 96% sensitivity and 96% specificity. Insulin is elevated and IGFBP-3/PSA is reduced with increase prostate size in BPH cases. Copyright © 2017 Elsevier B.V. All rights reserved.

Metformin use and risk of prostate cancer: results from the REDUCE study.

PubMed

Feng, Tom; Sun, Xizi; Howard, Lauren E; Vidal, Adriana C; Gaines, Alexis R; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freedland, Stephen J

2015-11-01

The role of metformin in prostate cancer chemoprevention remains unclear. REDUCE, which followed biopsy-negative men with protocol-dictated PSA-independent biopsies at 2- and 4-years, provides an opportunity to evaluate the link between metformin use and prostate cancer diagnosis with minimal confounding from screening biases. In diabetic men from REDUCE, we tested the association between metformin use, use of other antidiabetic medications, versus no antidiabetic medication use, and prostate cancer diagnosis as well as prostate cancer grade (low-grade Gleason 4-6 and high-grade Gleason 7-10) using logistic regression. Of the 540 diabetic men with complete data, 205 (38%) did not report use of any antidiabetic medications, 141 (26%) reported use of at least one antidiabetic medication other than metformin, and 194 (36%) reported use of metformin. During the 4-year study, 122 men (23%) were diagnosed with prostate cancer. After adjusting for various clinical and demographic characteristics, we found that metformin use was not significantly associated with total (OR, 1.19; P = 0.50), low- (OR, 1.01; P = 0.96), or high-grade (OR, 1.83; P = 0.19) prostate cancer diagnosis. Likewise, there was no significant association between the use of non-metformin antidiabetic medications and prostate cancer risk in both crude (OR, 1.02; P = 0.95) and multivariable analysis (OR, 0.85; P = 0.56). Furthermore, the interactions between antidiabetic medication use and BMI, geographic location, coronary artery disease, smoking, and treatment group were not significant (all P > 0.05). Among diabetic men with a negative prestudy biopsy who all underwent biopsies largely independent of PSA, metformin use was not associated with reduced risk of prostate cancer diagnosis. ©2015 American Association for Cancer Research.

Growth hormone-releasing hormone antagonists reduce prostatic enlargement and inflammation in carrageenan-induced chronic prostatitis.

PubMed

Popovics, Petra; Cai, Renzhi; Sha, Wei; Rick, Ferenc G; Schally, Andrew V

2018-05-21

Inflammation plays a key role in the etiology of benign prostatic hyperplasia (BPH) through multiple pathways involving the stimulation of proliferation by cytokines and growth factors as well as the induction of the focal occurrence of epithelial-to-mesenchymal transition (EMT). We have previously reported that GHRH acts as a prostatic growth factor in experimental BPH and in autoimmune prostatitis models and its blockade with GHRH antagonists offer therapeutic approaches for these conditions. Our current study was aimed at the investigation of the beneficial effects of GHRH antagonists in λ-carrageenan-induced chronic prostatitis and at probing the downstream molecular pathways that are implicated in GHRH signaling. To demonstrate the complications triggered by recurrent/chronic prostatic inflammation in Sprague-Dawley rats, 50 μL 3% carrageenan was injected into both ventral prostate lobes two times, 3 weeks apart. GHRH antagonist, MIA-690, was administered 5 days after the second intraprostatic injection at 20 μg daily dose for 4 weeks. GHRH-induced signaling events were identified in BPH-1 and in primary prostate epithelial (PrEp) cells at 5, 15, 30, and 60 min with Western blot. Inflammation induced prostatic enlargement and increased the area of the stromal compartment whereas treatment with the GHRH antagonist significantly reduced these effects. This beneficial activity was consistent with a decrease in prostatic GHRH, inflammatory marker COX-2, growth factor IGF-1 and inflammatory and EMT marker TGF-β1 protein levels and the expression of multiple genes related to EMT. In vitro, GHRH stimulated multiple pathways involved in inflammation and growth in both BPH-1 and PrEp cells including NFκB p65, AKT, ERK1/2, EGFR, STAT3 and increased the levels of TGF-β1 and Snail/Slug. Most interestingly, GHRH also stimulated the transactivation of the IGF receptor. The study demonstrates that GHRH antagonists could be beneficial for the treatment of

Intra-vesical Prostatic Protrusion (IPP) Can Be Reduced by Prostatic Artery Embolization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Yen-Ting, E-mail: ymerically@gmail.com; Amouyal, Grégory, E-mail: gregamouyal@hotmail.com; Thiounn, Nicolas, E-mail: nicolas.thiounn@egp.aphp.fr

BackgroundProstate artery embolization (PAE) is a new approach to improve lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia. PAE results in global reduction of prostate volume (PV). There are no data available on the efficacy of PAE in reducing intra-vesical prostatic protrusion (IPP), an anatomic feature that is clinically related with bladder outlet obstruction and LUTS.ObjectiveTo assess the results of PAE in patients with significant IPP due to median lobe hyperplasia and to compare the IPSS decrease and IPP change.Material and MethodsProspective analysis of 18 consecutive patients with significant IPP (>5 mm) related to median lobe hyperplasia undergoing PAEmore » using 30–500-μm-calibrated trisacryl microspheres. We measured IPP on sagittal T2-weighted images before and 3 months after PAE. IPSS and clinical results were also evaluated at 3 months.ResultsPAE resulted in significant IPP reduction (1.57 cm ± 0.55 before PAE and 1.30 cm ± 0.46 after PAE, p = 0.0005) (Fig. 1) with no complication. IPSS, quality of life (QoL), total prostate-specific antigen (PSA) level, and PV showed significant reduction after PAE, and maximum urinary flow rate (Q{sub max}) showed significant increase after PAE. No significant change of International Index of Erectile Function (IIEF) for clinical evaluation after PAE. A significant correlation was found between the IPP change and the IPSS change (r = 0.636, p = 0.0045).ConclusionPatients had significant IPP reduction as well as significant symptomatic improvement after PAE, and these improvements were positively correlated.« less

N-Butanol and Aqueous Fractions of Red Maca Methanolic Extract Exerts Opposite Effects on Androgen and Oestrogens Receptors (Alpha and Beta) in Rats with Testosterone-Induced Benign Prostatic Hyperplasia.

PubMed

Fano, Diego; Vásquez-Velásquez, Cinthya; Gonzales-Castañeda, Cynthia; Guajardo-Correa, Emanuel; Orihuela, Pedro A; Gonzales, Gustavo F

2017-01-01

Benign Prostatic Hyperplasia (BPH) affects, worldwide, 50% of 60-year-old men. The Peruvian plant red maca (Lepidium meyenii) inhibits BPH in rodents. This study aimed to determine the effects of methanolic red maca extract and its n-butanol and aqueous fractions on expression of androgen and oestrogen receptors in rats with testosterone enanthate-induced BPH. Thirty-six rats in six groups were studied. Control group received 2 mL of vehicle orally and 0.1 mL of propylene glycol intramuscularly. The second group received vehicle orally and testosterone enanthate (TE) (25 mg/0.1 mL) intramuscularly in days 1 and 7. The other four groups were BPH-induced with TE and received, during 21 days, 3.78 mg/mL of finasteride, 18.3 mg/mL methanol extract of red maca, 2 mg/mL of n-butanol fraction, or 16.3 mg/mL of aqueous fraction from red maca. Treatments with red maca extract and its n-butanol but not aqueous fraction reduced prostate weight similar to finasteride. All maca treated groups restored the expression of ER β , but only the aqueous fraction increased androgen receptors and ER α . In conclusion, butanol fraction of red maca reduced prostate size in BPH by restoring expression of ER β without affecting androgen receptors and ER α . This effect was not observed with aqueous fraction of methanolic extract of red maca.

N-Butanol and Aqueous Fractions of Red Maca Methanolic Extract Exerts Opposite Effects on Androgen and Oestrogens Receptors (Alpha and Beta) in Rats with Testosterone-Induced Benign Prostatic Hyperplasia

PubMed Central

Vásquez-Velásquez, Cinthya

2017-01-01

Benign Prostatic Hyperplasia (BPH) affects, worldwide, 50% of 60-year-old men. The Peruvian plant red maca (Lepidium meyenii) inhibits BPH in rodents. This study aimed to determine the effects of methanolic red maca extract and its n-butanol and aqueous fractions on expression of androgen and oestrogen receptors in rats with testosterone enanthate-induced BPH. Thirty-six rats in six groups were studied. Control group received 2 mL of vehicle orally and 0.1 mL of propylene glycol intramuscularly. The second group received vehicle orally and testosterone enanthate (TE) (25 mg/0.1 mL) intramuscularly in days 1 and 7. The other four groups were BPH-induced with TE and received, during 21 days, 3.78 mg/mL of finasteride, 18.3 mg/mL methanol extract of red maca, 2 mg/mL of n-butanol fraction, or 16.3 mg/mL of aqueous fraction from red maca. Treatments with red maca extract and its n-butanol but not aqueous fraction reduced prostate weight similar to finasteride. All maca treated groups restored the expression of ERβ, but only the aqueous fraction increased androgen receptors and ERα. In conclusion, butanol fraction of red maca reduced prostate size in BPH by restoring expression of ERβ without affecting androgen receptors and ERα. This effect was not observed with aqueous fraction of methanolic extract of red maca. PMID:29375645

Lepidium meyenii (Maca) enhances the serum levels of luteinising hormone in female rats.

PubMed

Uchiyama, Fumiaki; Jikyo, Tamaki; Takeda, Ryosuke; Ogata, Misato

2014-02-03

Lepidium meyenii (Maca) is traditionally employed in the Andean region for its supposed fertility benefits. This study investigated the effect of Maca on the serum pituitary hormone levels during the pro-oestrus phase. Maca powder was made from the tubers of Lepidium meyenii Walp collected, dried, and reduced to powder at the plantation in Junín Plateau and was purchased from Yamano del Perú SAC. The Maca powder was identified by chemical profiling and taxonomic methods. Two groups of female Sprague-Dawley rats were provided feed with normal feed containing 5%, 25%, or 50% Maca powder ad libitum for 7 weeks. At 1800h of the proestrus stage, the rats were euthanised, and blood samples were collected for serum isolation. The serum pituitary hormone levels were measured using enzyme-linked immunosorbent assays (ELISAs). No significant differences in feed intake or growth rate were observed among the rats. During the pro-oestrus stage, a 4.5-fold increase (P<0.01) in luteinising hormone (LH) and a 19-fold increase (P<0.01) in follicle-stimulating hormone (FSH) were observed in the sera of rats fed with 50% Maca powder compared with the control rats. No significant differences were observed in the levels of the other pituitary hormones, including growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), and thyroid-stimulating hormone (TSH). A dose-dependent increase of LH serum levels was observed within the range of 3-30g Maca/kg. Furthermore, the enhancement of the LH serum levels was specific to the pro-oestrus LH surge. The present study demonstrates that Maca uniquely enhances the LH serum levels of pituitary hormones in female rats during the pro-oestrus LH surge and acts in a pharmacological, dose-dependent manner. These findings support the traditional use of Maca to enhance fertility and suggest a potential molecular mechanism responsible for its effects. © 2013 Elsevier Ireland Ltd. All rights reserved.

Various treatment options for benign prostatic hyperplasia: A current update

PubMed Central

Shrivastava, Alankar; Gupta, Vipin B.

2012-01-01

In benign prostatic hyperplasia (BPH) there will be a sudden impact on overall quality of life of patient. This disease occurs normally at the age of 40 or above and also is associated with sexual dysfunction. Thus, there is a need of update on current medications of this disease. The presented review provides information on medications available for BPH. Phytotherapies with some improvements in BPH are also included. Relevant articles were identified through a search of the English-language literature indexed on MEDLINE, PUBMED, Sciencedirect and the proceedings of scientific meetings. The search terms were BPH, medications for BPH, drugs for BPH, combination therapies for BPH, Phytotherapies for BPH, Ayurveda and BPH, BPH treatments in Ayurveda. Medications including watchful waitings, Alpha one adrenoreceptor blockers, 5-alpha reductase inhibitors, combination therapies including tamsulosin-dutasteride, doxazosin-finasteride, terazosin-finasteride, tolterodine-tamsulosin and rofecoxib-finasteride were found. Herbal remedies such as Cernilton, Saxifraga stolonifera, Zi-Shen Pill (ZSP), Orbignya speciosa, Phellodendron amurense, Ganoderma lucidum, Serenoa Repens, pumpkin extract and Lepidium meyenii (Red Maca) have some improvements on BPH are included. Other than these discussions on Ayurvedic medications, TURP and minimally invasive therapies (MITs) are also included. Recent advancements in terms of newly synthesized molecules are also discussed. Specific alpha one adrenoreceptor blockers such as tamsulosin and alfuzosin will remain preferred choice of urologists for symptom relief. Medications with combination therapies are still needs more investigation to establish as preference in initial stage for fast symptom relief reduced prostate growth and obviously reduce need for BPH-related surgery. Due to lack of proper evidence Phytotherapies are not gaining much advantage. MITs and TURP are expensive and are rarely supported by healthcare systems. PMID:22923974

Purification, characterization and biological activities of a polysaccharide from Lepidium meyenii leaves.

PubMed

Li, Shufang; Hao, Limin; Kang, Qiaozhen; Cui, Yinxin; Jiang, Hui; Liu, Xin; Lu, Jike

2017-10-01

The characteristics and biological activities of a novel polysaccharide from Lepidium meyenii leaves (LMLP) were investigated. LMLP was purified using DEAE-52 cellulose chromatography followed by SephadexG-100 chromatography. The average molecule weight of LMLP was 58.43kDa and it was composed of galactose, arabinose, rhamnose, glucose and mannose with a relative molar ratio of 5.51:4.05:1.15:0.77:0.01. Antioxidant activity results showed that LMLP presented an EC 50 of 3.72mg/mL in scavenging 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical, and it also had reducing power (OD700nm being 0.079 at 1mg/mL). Moreover, LMLP possessed the potential on stimulating immune response of RAW264.7 cells. It could promote proliferation, strengthen phagocytosis function, enhance the expression of CD80, and increase the secretion of nitric oxide (NO) in a dose-dependent manner. All of these results suggested that LMLP could be used as a natural ingredient for functional food. Copyright © 2017 Elsevier B.V. All rights reserved.

Serum cholesterol and risk of high-grade prostate cancer: results from the REDUCE study.

PubMed

Jamnagerwalla, Juzar; Howard, Lauren E; Allott, Emma H; Vidal, Adriana C; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freeman, Michael R; Freedland, Stephen J

2017-12-27

Epidemiologic evidence for a serum cholesterol-prostate cancer link is mixed. Prostate-specific antigen (PSA) is positively correlated with cholesterol, potentially increasing PSA-driven biopsy recommendations in men with high cholesterol, though biopsy compliance may be lower in men with comorbid conditions. These potential biases may affect PSA-driven biopsy rates and subsequent prostate cancer detection in men with high serum cholesterol. Our objective was to test the association between serum cholesterol and prostate cancer risk in men receiving PSA independent, study-mandated prostate biopsies. We conducted a post hoc analysis of data from 4974 non-statin users in REDUCE, a randomized trial in men with elevated PSA and a negative baseline biopsy. Men underwent 2- and 4-year trial-mandated prostate biopsies. Associations between baseline serum levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and prostate cancer risk, overall and by Gleason grade (<7 vs. ≥7), were examined using multivariable logistic regression. High total serum cholesterol was associated with an increased risk of high-grade prostate cancer diagnosis (OR per 10 mg/dL 1.05; 95% CI 1.00-1.09; p = 0.048), but cholesterol was unrelated to either overall or low-grade prostate cancer risk (p-values >0.185). There was no association between serum LDL and overall, low- or high-grade prostate cancer risk (p-values >0.137). In contrast, elevated serum HDL was associated with increased risk of both overall (OR per 10 mg/dL 1.08; 95% CI 1.01-1.16; p = 0.033) and high-grade prostate cancer (OR per 10 mg/dL 1.14; 95% CI 1.01-1.28; p = 0.034). In REDUCE, where all men received PSA independent, trial-mandated biopsies thus ensuring complete prostate cancer ascertainment, high total serum cholesterol and high HDL were associated with increased risk of high-grade prostate cancer, supporting a cholesterol-prostate cancer link.

The Association between Phosphodiesterase Type 5 Inhibitors and Prostate Cancer: Results from the REDUCE Study.

PubMed

Jamnagerwalla, Juzar; Howard, Lauren E; Vidal, Adriana C; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freedland, Stephen J

2016-09-01

Despite routine use of phosphodiesterase type 5 inhibitor to treat erectile dysfunction the role in prostate cancer chemoprevention remains unclear. Only a few studies have explored the link between phosphodiesterase type 5 inhibitor use and prostate cancer. We tested the association between phosphodiesterase type 5 inhibitor and prostate cancer risk in the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) trial. REDUCE was a 4-year multicenter study testing the effect of daily dutasteride on prostate cancer risk in men with prostate specific antigen 2.5 to 10.0 ng/ml and negative biopsy who underwent study mandated biopsies at 2 and 4 years. The association of phosphodiesterase type 5 inhibitor with overall prostate cancer risk and disease grade (Gleason 2-6 and 7-10) was examined using adjusted logistic and multinomial regression analysis. Secondary analysis was performed to explore the association between phosphodiesterase type 5 inhibitor and prostate cancer risk in North American men, given the significantly higher use of phosphodiesterase type 5 inhibitor in these subjects. Phosphodiesterase type 5 inhibitor was not associated with prostate cancer diagnosis (OR 0.90, 95% CI 0.68-1.20, p = 0.476), low grade disease (OR 0.93, 95% CI 0.67-1.27, p = 0.632) or high grade disease (OR 0.85, 95% CI 0.51-1.39, p = 0.508). An inverse trend was seen between phosphodiesterase type 5 inhibitor and prostate cancer diagnosis in North American men but this was not statistically significant (OR 0.67, 95% CI 0.42-1.07, p = 0.091). Phosphodiesterase type 5 inhibitor use was not associated with decreased prostate cancer diagnoses on post-hoc analysis of REDUCE. In North American men, who had much higher baseline use of phosphodiesterase type 5 inhibitor, this treatment was associated with an inverse trend of prostate cancer diagnosis that approached but did not reach statistical significance. Copyright © 2016 American Urological Association Education and

Is the hype around the reproductive health claims of maca (Lepidium meyenii Walp.) justified?

PubMed

Beharry, Shruti; Heinrich, Michael

2018-01-30

Maca - Lepidium meyenii Walp. has been cultivated and used by Andean people for over 1300-2000 years in Peru as food and medicine. Starting in the late 1990's it has developed into an important herbal medicine in China and is now cultivated there widely, too AIM OF STUDY: This study aims to provide an insight into the emergence of maca on the global market as an alternative remedy to treat reproductive health related problems in both men and women and to critically assess these health claims. A search of electronic databases such as EMBASE and a hand-search was done to acquire peer-reviewed articles and reports about maca. Lepidium meyenii is used traditionally as a tonic, fertility enhancer for both humans and cattle, and to treat a variety of ailments such as rheumatism, respiratory disorders and anaemia among others. Maca root is cooked, baked, fermented as a drink and made into porridge. In the last twenty years, maca was introduced onto the global market and demand has dramatically grown over this time with its promotion on the internet, as the 'Peruvian Ginseng' for libido and fertility enhancement. It has also been said to treat menopausal symptoms, erectile dysfunction and benign prostatic hyperplasia. The sky-rocketing demand for the plant has seen a shift from traditional cultivation methods to mass production practices with the use of fertilisers and also pesticides; as maca is now grown in areas other than the Andes such as in the Yunnan province in China. This can potentially affect the phytochemistry and composition of the plant and thus, the quality, safety and efficacy of maca products. Meanwhile, research into maca's medicinal properties has followed the spike in popularity of maca and has been focused mainly on maca's aphrodisiac and fertility enhancing properties. So far, the in vivo studies and clinical trials conducted have yielded inconclusive results. Some of the key limitations reside in methodology and sample size. Chemical profiling, led

Reduced mitochondrial DNA content associates with poor prognosis of prostate cancer in African American men.

PubMed

Koochekpour, Shahriar; Marlowe, Timothy; Singh, Keshav K; Attwood, Kristopher; Chandra, Dhyan

2013-01-01

Reduction or depletion of mitochondrial DNA (mtDNA) has been associated with cancer progression. Although imbalanced mtDNA content is known to occur in prostate cancer, differences in mtDNA content between African American (AA) and Caucasian American (CA) men are not defined. We provide the first evidence that tumors in AA men possess reduced level of mtDNA compared to CA men. The median tumor mtDNA content was reduced in AA men. mtDNA content was also reduced in normal prostate tissues of AA men compared to CA men, suggesting a possible predisposition to cancer in AA men. mtDNA content was also reduced in benign prostatic hyperplasia (BPH) tissue from AA men. Tumor and BPH tissues from patients ≥ 60 years of age possess reduced mtDNA content compared to patients <60 years of age. In addition, mtDNA content was higher in normal tissues from patients with malignant T3 stage disease compared to patients with T2 stage disease. mtDNA levels in matched normal prostate tissues were nearly doubled in Gleason grade of >7 compared to ≤ 7, whereas reduced mtDNA content was observed in tumors of Gleason grade >7 compared to ≤ 7. Together, our data suggest that AA men possess lower mtDNA levels in normal and tumor tissues compared to CA men, which could contribute to higher risk and more aggressive prostate cancer in AA men.

A Double-Blind Placebo-Controlled Randomized Clinical Trial With Magnesium Oxide to Reduce Intrafraction Prostate Motion for Prostate Cancer Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lips, Irene M., E-mail: i.m.lips@umcutrecht.nl; Gils, Carla H. van; Kotte, Alexis N.T.J.

2012-06-01

Purpose: To investigate whether magnesium oxide during external-beam radiotherapy for prostate cancer reduces intrafraction prostate motion in a double-blind, placebo-controlled randomized trial. Methods and Materials: At the Department of Radiotherapy, prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. The primary outcome was the proportion of patients with clinically relevant intrafraction prostate motion, defined as the proportion of patients who demonstrated in {>=}50% of the fractions an intrafraction motion outside a range of 2 mm. Secondarymore » outcome measures included quality of life and acute toxicity. Results: In total, 46 patients per treatment arm were enrolled. The primary endpoint did not show a statistically significant difference between the treatment arms with a percentage of patients with clinically relevant intrafraction motion of 83% in the magnesium oxide arm as compared with 80% in the placebo arm (p = 1.00). Concerning the secondary endpoints, exploratory analyses demonstrated a trend towards worsened quality of life and slightly more toxicity in the magnesium oxide arm than in the placebo arm; however, these differences were not statistically significant. Conclusions: Magnesium oxide is not effective in reducing the intrafraction prostate motion during external-beam radiotherapy, and therefore there is no indication to use it in clinical practice for this purpose.« less

Feeding hydroalcoholic extract powder of Lepidium meyenii (maca) increases serum testosterone concentration and enhances steroidogenic ability of Leydig cells in male rats.

PubMed

Ohta, Y; Yoshida, K; Kamiya, S; Kawate, N; Takahashi, M; Inaba, T; Hatoya, S; Morii, H; Takahashi, K; Ito, M; Ogawa, H; Tamada, H

2016-04-01

Although Lepidium meyenii (maca), a plant growing in Peru's central Andes, has been traditionally used for enhancing fertility and reproductive performance in domestic animals and human beings, effects of maca on reproductive organs are still unclear. This study examined whether feeding the hydroalcoholic extract powder of maca for 6 weeks affects weight of the reproductive organs, serum concentrations of testosterone and luteinising hormone (LH), number and cytoplasmic area of immunohistochemically stained Leydig cells, and steroidogenesis of cultured Leydig cells in 8-week-old male rats. Feeding the extract powder increased weight of seminal vesicles, serum testosterone level and cytoplasmic area of Leydig cells when compared with controls. Weight of prostate gland, serum LH concentration and number of Leydig cells were not affected by the maca treatment. The testosterone production by Leydig cells significantly increased when cultured with 22R-hydroxycholesterol or pregnenolone and tended to increase when cultured with hCG by feeding the extract powder. The results show that feeding the hydroalcoholic extract powder of maca for 6 weeks increases serum testosterone concentration associated with seminal vesicle stimulation in male rats, and this increase in testosterone level may be related to the enhanced ability of testosterone production by Leydig cells especially in the metabolic process following cholesterol. © 2015 Blackwell Verlag GmbH.

Metformin for Reducing Racial/Ethnic Difference in Prostate Cancer Incidence for Men with Type II Diabetes.

PubMed

Wang, Chen-Pin; Lehman, Donna M; Lam, Yui-Wing F; Kuhn, John G; Mahalingam, Devalingam; Weitman, Steven; Lorenzo, Carlos; Downs, John R; Stuart, Elizabeth A; Hernandez, Javier; Thompson, Ian M; Ramirez, Amelie G

2016-10-01

Racial/ethnic disparity in prostate cancer is under studied in men with diabetes who are at a higher risk of aggressive prostate cancer. This study assessed the race/ethnic disparity in prostate cancer incidence for men with type II diabetes (T2D) and whether the impact of metformin on prostate cancer incidence varied by race/ethnicity. We conducted a retrospective study in 76,733 male veterans with T2D during 2003 to 2012. Cox proportional hazards model adjusting for covariates and propensity scores of metformin use and race/ethnic group membership was utilized to compute the HR of prostate cancer incidence associated with race/ethnicity and compare HR associated with metformin use between race/ethnic groups. Mean follow-up was 6.4 ± 2.8 years; 7% were Hispanics; 17% were African Americans (AA); mean age was 67.8 ± 9.8 years; 5.2% developed prostate cancer; and 38.9% used metformin. Among these diabetic men without metformin use, prostate cancer incidence was higher in Hispanics and AA than in non-Hispanic White (NHW). Use of metformin alone or metformin + statins was associated with a greater prostate cancer incidence reduction in Hispanics compared with NHW, but not between AA and NHW. Use of metformin + finasteride was associated with a greater prostate cancer incidence reduction in Hispanics and AA compared with NHW. Our results suggested that metformin treatment could be a potential strategy to reduce prostate cancer incidence in the minority populations who are at high risk for fatal prostate cancer. It will be important to further examine the pleiotropic effects of metformin in multi-race/ethnic prospective studies to better inform clinical management and potentially reduce racial/ethnic disparity in prostate cancer incidence among diabetic men. Cancer Prev Res; 9(10); 779-87. ©2016 AACR. ©2016 American Association for Cancer Research.

Finasteride Reduces the Risk of Incident Clinical Benign Prostatic Hyperplasia

PubMed Central

Parsons, J. Kellogg; Schenk, Jeannette M.; Arnold, Kathryn B.; Messer, Karen; Till, Cathee; Thompson, Ian M.; Kristal, Alan R.

2014-01-01

Background Despite the high prevalence of clinical benign prostatic hyperplasia (BPH) among older men, there remains a notable absence of studies focused on BPH prevention. Objective To determine if finasteride prevents incident clinical BPH in healthy older men. Design, setting, and participants Data for this study are from the Prostate Cancer Prevention Trial. After excluding those with a history of BPH diagnosis or treatment, or an International Prostate Symptom Score (IPSS) ≥8 at study entry, 9253 men were available for analysis. Outcome measurements and statistical analysis The primary outcome was incident clinical BPH, defined as the initiation of medical treatment, surgery, or sustained, clinically significant urinary symptoms (IPSS >14). Finasteride efficacy was estimated using Cox proportional regression models to generate hazards ratios (HRs). Results and limitations Mean length of follow-up was 5.3 yr. The rate of clinical BPH was 19 per 1000 person-years in the placebo arm and 11 per 1000 person-years in the finasteride arm (p < 0.001). In a covariate-adjusted model, finasteride reduced the risk of incident clinical BPH by 40% (HR: 0.60; 95% confidence interval, 0.51–0.69; p < 0.001). The effect of finasteride on incident clinical BPH was attenuated in men with a body mass index ≥30 kg/m2 (pinteraction = 0.04) but otherwise did not differ significantly by physical activity, age, race, current diabetes, or current smoking. The post hoc nature of the analysis is a potential study limitation. Conclusions Finasteride substantially reduces the risk of incident clinical BPH in healthy older men. These results should be considered in formulating recommendations for the use of finasteride to prevent prostate diseases in asymptomatic older men. PMID:22459892

Resveratrol Reduces Prostate Cancer Growth and Metastasis by Inhibiting the Akt/MicroRNA-21 Pathway

PubMed Central

Sheth, Sandeep; Jajoo, Sarvesh; Kaur, Tejbeer; Mukherjea, Debashree; Sheehan, Kelly; Rybak, Leonard P.; Ramkumar, Vickram

2012-01-01

The consumption of foods containing resveratrol produces significant health benefits. Resveratrol inhibits cancer by reducing cell proliferation and metastasis and by inducing apoptosis. These actions could be explained by its ability to inhibit (ERK-1/2), Akt and suppressing the levels of estrogen and insulin growth factor -1 (IGF-1) receptor. How these processes are manifested into the antitumor actions of resveratrol is not clear. Using microarray studies, we show that resveratrol reduced the expression of various prostate-tumor associated microRNAs (miRs) including miR-21 in androgen-receptor negative and highly aggressive human prostate cancer cells, PC-3M-MM2. This effect of resveratrol was associated with reduced cell viability, migration and invasiveness. Additionally, resveratrol increased the expression of tumor suppressors, PDCD4 and maspin, which are negatively regulated by miR-21. Short interfering (si) RNA against PDCD4 attenuated resveratrol’s effect on prostate cancer cells, and similar effects were observed following over expression of miR-21 with pre-miR-21 oligonucleotides. PC-3M-MM2 cells also exhibited high levels of phospho-Akt (pAkt), which were reduced by both resveratrol and LY294002 (a PI3-kinase inhibitor). MiR-21 expression in these cells appeared to be dependent on Akt, as LY294002 reduced the levels of miR-21 along with a concurrent increase in PDCD4 expression. These in vitro findings were further corroborated in a severe combined immunodeficient (SCID) mouse xenograft model of prostate cancer. Oral administration of resveratrol not only inhibited the tumor growth but also decreased the incidence and number of metastatic lung lesions. These tumor- and metastatic-suppressive effects of resveratrol were associated with reduced miR-21 and pAkt, and elevated PDCD4 levels. Similar anti-tumor effects of resveratrol were observed in DU145 and LNCaP prostate cancer cells which were associated with suppression of Akt and PDCD4, but

[Reduced zinc concentration in expressed prostatic secretion relates to the pain symptoms of types Ⅲ and Ⅳ prostatitis].

PubMed

Mo, Lin-Jian; Chen, Xi; Wang, Xiao-Ming; Li, Guang-Yu; Zhang, Xun; Huang, Shan; Xie, Zhi-Bin; Mo, Zeng-Nan

2016-06-01

To determine the zinc levels in the expressed prostatic secretion (EPS) of the patients with different types of chronic nonbacterial prostatitis, and explore the reference value of zinc concentration in EPS in the diagnosis and treatment of prostatitis. We collected EPS samples from 35 healthy men and 173 patients with chronic nonbacterial prostatitis, including 65 cases of type ⅢA, 69 cases of type ⅢB, and 39 cases of type Ⅳ, according to the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). We compared the zinc levels in the EPS samples among different groups and analyzed the correlations of zinc concentration with the NIH-CPSI scores, WBC count, pH value, and age of the subjects. The participants were aged 17－65 (32.5±8.5) years. The zinc concentrations in the EPS were significantly lower in the ⅢA (［162.2±10.8］ μg/ml) and ⅢB (［171.2±12.0］ μg/ml) than in the Ⅳ (［234.6±17.9］ μg/ml) (P<0.05 ) and the control group (［259.5±14.6］ μg/ml) (P<0.05 ). The zinc level was correlated negatively with the NIH-CPSI pain score (r=－0.248, P<0.01), quality of life score (r=－0.232, P<0.01), severity score (r=－0.270, P<0.01), total NIH-CPSI score (r=－0.281, P<0.01), and the pH value in EPS (r=－0.208, P<0.01), but showed no correlation with the WBC count and age of the subjects. The reduced zinc concentration in the EPS of the patients with chronic nonbacterial prostatitis may be associated with the pain symptoms of the disease, which suggests the potential reference value of measuring the zinc concentration in EPS in the diagnosis and treatment of prostatitis.

Sunitinib reduces tumor hypoxia and angiogenesis, and radiosensitizes prostate cancer stem-like cells.

PubMed

Diaz, Roque; Nguewa, Paul A; Redrado, Miriam; Manrique, Irene; Calvo, Alfonso

2015-08-01

The need for new treatments for advanced prostate cancer has fostered the experimental use of targeted therapies. Sunitinib is a multi-tyrosine kinase inhibitor that mainly targets membrane-bound receptors of cells within the tumor microenvironment, such as endothelial cells and pericytes. However, recent studies suggest a direct effect on tumor cells. In the present study, we have evaluated both direct and indirect effects of Sunitinib in prostate cancer and how this drug regulates hypoxia, using in vitro and in vivo models. We have used both in vitro (PC-3, DU145, and LNCaP cells) and in vivo (PC-3 xenografts) models to study the effect of Sunitinib in prostate cancer. Analysis of hypoxia based on HIF-1α expression and FMISO uptake was conducted. ALDH activity was used to analyze cancer stem cells (CSC). Sunitinib strongly reduced proliferation of PC-3 and DU-145 cells in a dose dependent manner, and decreased levels of p-Akt, p-Erk1/2, and Id-1, compared to untreated cells. A 3-fold reduction in tumor growth was also observed (P < 0.001 with respect to controls). Depletion of Hif-1α levels in vitro and a decrease in FMISO uptake in vivo showed that Sunitinib inhibits tumor hypoxia. When combined with radiotherapy, this drug enhanced cell death in vitro and in vivo, and significantly decreased CD-31, PDGFRβ, Hif-1α, Id1, and PCNA protein levels (whereas apoptosis was increased) in tumors as compared to controls or single-therapy treated mice. Moreover, Sunitinib reduced the number of ALDH + cancer stem-like cells and sensitized these cells to radiation-mediated loss of clonogenicity. Our results support the use of Sunitinib in prostate cancer and shows that both hypoxia and cancer stem cells are involved in the effect elicited by this drug. Combination of Sunitinib with radiotherapy warrants further consideration to reduce prostate cancer burden. © 2015 Wiley Periodicals, Inc.

Protective Effects of Lepidium meyenii (Maca) Aqueous Extract and Lycopene on Testosterone Propionate-Induced Prostatic Hyperplasia in Mice.

PubMed

Zou, Ying; Aboshora, Waleed; Li, Jing; Xiao, Tiancun; Zhang, Lianfu

2017-08-01

The inhibitory effect of maca extractant, lycopene, and their combination was evaluated in benign prostatic hyperplasia (BPH) mice induced by testosterone propionate. Mice were divided into a saline group, solvent control group and testosterone propionate-induced BPH mice [BPH model group, solvent BPH model group, benzyl glucosinolate group (1.44 mg/kg), maca group (60 mg/kg), lycopene treated (15, 5, and 2.5 mg/kg), maca (30 mg/kg) combine lycopene treated (7.5, 2.5, and 1.25 mg/kg), and finasteride treated]. Benzyl glucosinolate was used in order to evaluate its pharmacological activity on BPH to find out whether it is the major active component of maca aqueous extract. Finasteride was used as positive control. The compounds were administered once for 30 successive days. Compared with solvent BPH model group, BPH mice fed with maca (30 mg/kg) and lycopene (7.5 mg/kg) combination exhibited significant reductions in the prostatic index, prostatic acid phospatase, estradiol, testosterone, and dihydrotestosterone levels in serum. They also had similar histological compared with those aspects observed in the mice in the solvent control group. The results indicated that combination of maca and lycopene synergistically inhibits BPH in mice. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

(-)-Gossypol reduces invasiveness in metastatic prostate cancer cells

USDA-ARS?s Scientific Manuscript database

Acquisition of metastatic ability by prostatic cancer cells is the most lethal aspect of prostatic cancer progression. (-)-Gossypol, a polyphenolic compound present in cottonseeds, possesses anti-proliferation and pro-apoptotic effects in various cancer cells. In this study, the differences betwee...

Vinclozolin Exposure in Utero Induces Postpubertal Prostatitis and Reduces Sperm Production via a Reversible Hormone-Regulated Mechanism

PubMed Central

Cowin, Prue A.; Gold, Elspeth; Aleksova, Jasna; O'Bryan, Moira K.; Foster, Paul M. D.; Scott, Hamish S.; Risbridger, Gail P.

2010-01-01

Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high affinity to the androgen receptor (AR) and blocks the action of gonadal hormones on male reproductive organs. An alternative mechanism of action of Vinclozolin involves transgenerational effects on the male reproductive tract. We previously reported in utero Vinclozolin exposure-induced prostatitis (prostate inflammation) in postpubertal rats concurrent with down-regulation of AR and increased nuclear factor-κB activation. We postulated the male reproductive abnormalities induced by in utero Vinclozolin exposure could be reversed by testosterone supplementation, in contrast to the permanent modifications involving DNA methyltransferases (Dnmts) described by others. To test this hypothesis, we administered high-dose testosterone at puberty to Vinclozolin-treated rats and determined the effect on anogenital distance (AGD); testicular germ cell apoptosis, concentration of elongated spermatids, and the onset of prostatitis. Concurrently we examined Dnmt1, −3A, −3B, and −3L mRNA expression. Consistent with previous reports, in utero exposure to Vinclozolin significantly reduced AGD, increased testicular germ cell apoptosis 3-fold, reduced elongated spermatid number by 40%, and induced postpubertal prostatitis in 100% of exposed males. Administration of high-dose testosterone (25 mg/kg) at puberty normalized AGD, reduced germ cell apoptosis, and restored elongated spermatid number. Testosterone restored AR and nuclear factor-κB expression in the prostate and abolished Vinclozolin-induced prostatitis. Altered Dnmt expression was evident with in utero Vinclozolin exposure and was not normalized after testosterone treatment. These data demonstrate in utero Vinclozolin-induced male reproductive tract abnormalities are AR mediated and reversible and involve a mechanism independent of Dnmt expression. PMID:20056826

Vinclozolin exposure in utero induces postpubertal prostatitis and reduces sperm production via a reversible hormone-regulated mechanism.

PubMed

Cowin, Prue A; Gold, Elspeth; Aleksova, Jasna; O'Bryan, Moira K; Foster, Paul M D; Scott, Hamish S; Risbridger, Gail P

2010-02-01

Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high affinity to the androgen receptor (AR) and blocks the action of gonadal hormones on male reproductive organs. An alternative mechanism of action of Vinclozolin involves transgenerational effects on the male reproductive tract. We previously reported in utero Vinclozolin exposure-induced prostatitis (prostate inflammation) in postpubertal rats concurrent with down-regulation of AR and increased nuclear factor-kappaB activation. We postulated the male reproductive abnormalities induced by in utero Vinclozolin exposure could be reversed by testosterone supplementation, in contrast to the permanent modifications involving DNA methyltransferases (Dnmts) described by others. To test this hypothesis, we administered high-dose testosterone at puberty to Vinclozolin-treated rats and determined the effect on anogenital distance (AGD); testicular germ cell apoptosis, concentration of elongated spermatids, and the onset of prostatitis. Concurrently we examined Dnmt1, -3A, -3B, and -3L mRNA expression. Consistent with previous reports, in utero exposure to Vinclozolin significantly reduced AGD, increased testicular germ cell apoptosis 3-fold, reduced elongated spermatid number by 40%, and induced postpubertal prostatitis in 100% of exposed males. Administration of high-dose testosterone (25 mg/kg) at puberty normalized AGD, reduced germ cell apoptosis, and restored elongated spermatid number. Testosterone restored AR and nuclear factor-kappaB expression in the prostate and abolished Vinclozolin-induced prostatitis. Altered Dnmt expression was evident with in utero Vinclozolin exposure and was not normalized after testosterone treatment. These data demonstrate in utero Vinclozolin-induced male reproductive tract abnormalities are AR mediated and reversible and involve a mechanism independent of Dnmt expression.

Green tea extract (epigallocatechin-3-gallate) reduces efficacy of radiotherapy on prostate cancer cells.

PubMed

Thomas, Francis; Holly, Jeff M P; Persad, Rajendra; Bahl, Amit; Perks, Claire M

2011-08-01

To assess the influence of epigallocatechin-3-gallate (EGCG) on the efficacy of ionizing radiation on prostate cancer cells because of the increased use of dietary interventions, especially by patients with prostate cancer. Radiotherapy is used to treat localized prostate cancer. Some people consume green tea (EGCG) as a chemopreventive agent against prostate cancer. Green tea can act as an antioxidant and induce superoxide dismutase enzymes, which could scavenge the free oxygen radicals generated by radiotherapy. Prostate cancer cell line DU145 cells were treated with EGCG or radiotherapy, or both. Cell death was assessed using trypan blue cell counting, and apoptosis was confirmed by assessing poly (adenosine phosphate ribose) polymerase cleavage. The antioxidant potential was assessed using Western immunoblotting for manganese superoxide dismutase and copper zinc superoxide dismutase enzymes. Radiotherapy was delivered using a linear accelerator. Cell cycle analysis was performed using flow cytometry. Radiotherapy at 3.5 Gy induced a 5.9-fold increase in apoptosis of DU145 cells. Subapoptotic doses of EGCG (1.5-7.5 μM) significantly reduced ionizing radiation-induced apoptosis (P < .001), with the inhibitory effect of EGCG on ionizing radiation being most effective when added 30 minutes before radiotherapy (P < .001). In addition, when radiotherapy and EGCG were used together, an approximate 1.5-fold increase in manganese superoxide dismutase levels was seen compared with the control and a 2-fold increase compared with radiotherapy alone. Radiotherapy is effective in inducing apoptosis in DU145 cells, but its effect was significantly reduced in the presence of EGCG, and this was associated with an increase in the induction of manganese superoxide dismutase. Copyright © 2011 Elsevier Inc. All rights reserved.

Loss of Sirt1 Promotes Prostatic Intraepithelial Neoplasia, Reduces Mitophagy, and Delays Park2 Translocation to Mitochondria

PubMed Central

Di Sante, Gabriele; Pestell, Timothy G.; Casimiro, Mathew C.; Bisetto, Sara; Powell, Michael J.; Lisanti, Michael P.; Cordon-Cardo, Carlos; Castillo-Martin, Mireia; Bonal, Dennis M.; Debattisti, Valentina; Chen, Ke; Wang, Liping; He, Xiaohong; McBurney, Michael W.; Pestell, Richard G.

2016-01-01

Prostatic intraepithelial neoplasia is a precursor to prostate cancer. Herein, deletion of the NAD+-dependent histone deacetylase Sirt1 induced histological features of prostatic intraepithelial neoplasia at 7 months of age; these features were associated with increased cell proliferation and enhanced mitophagy. In human prostate cancer, lower Sirt1 expression in the luminal epithelium was associated with poor prognosis. Genetic deletion of Sirt1 increased mitochondrial superoxide dismutase 2 (Sod2) acetylation of lysine residue 68, thereby enhancing reactive oxygen species (ROS) production and reducing SOD2 activity. The PARK2 gene, which has several features of a tumor suppressor, encodes an E3 ubiquitin ligase that participates in removal of damaged mitochondria via mitophagy. Increased ROS in Sirt1−/− cells enhanced the recruitment of Park2 to the mitochondria, inducing mitophagy. Sirt1 restoration inhibited PARK2 translocation and ROS production requiring the Sirt1 catalytic domain. Thus, the NAD+-dependent inhibition of SOD2 activity and ROS by SIRT1 provides a gatekeeper function to reduce PARK2-mediated mitophagy and aberrant cell survival. PMID:25529796

Liposome encapsulation of curcumin and resveratrol in combination reduces prostate cancer incidence in PTEN knockout mice.

PubMed

Narayanan, Narayanan K; Nargi, Dominick; Randolph, Carla; Narayanan, Bhagavathi A

2009-07-01

Increasing interest in the use of phytochemicals to reduce prostate cancer led us to investigate 2 potential agents, curcumin and resveratrol as preventive agents. However, there is concern about the bioavailability of these agents pertinent to the poor absorption and thereby limiting its clinical use. With the view to improve their bioavailability, we used the liposome encapsulated curcumin, and resveratrol individually and in combination in male B6C3F1/J mice. Further, we examined the chemopreventive effect of liposome encapsulated curcumin and resveratrol in combination in prostate-specific PTEN knockout mice. In vitro assays using PTEN-CaP8 cancer cells were performed to investigate the combined effects curcumin with resveratrol on (i) cell growth, apoptosis and cell cycle (ii) impact on activated p-Akt, cyclin D1, m-TOR and androgen receptor (AR) proteins involved in tumor progression. HPLC analysis of serum and prostate tissues showed a significant increase in curcumin level when liposome encapsulated curcumin coadministered with liposomal resveratrol (p < 0.001). Combination of liposomal forms of curcumin and resveratrol significantly decreased prostatic adenocarcinoma in vivo (p < 0.001). In vitro studies revealed that curcumin plus resveratrol effectively inhibit cell growth and induced apoptosis. Molecular targets activated due to the loss of phosphatase and tensin homolog (PTEN) including p-Akt, cyclin D1, mammalian target of rapamycin and AR were downregulated by these agents in combination. Findings from this study for the first time provide evidence on phytochemicals in combination to enhance chemopreventive efficacy in prostate cancer. These findings clearly suggest that phytochemicals in combination may reduce prostate cancer incidence due to the loss of the tumor suppressor gene PTEN.

Repeat prostate-specific antigen (PSA) test before prostate biopsy: a 20% decrease in PSA values is associated with a reduced risk of cancer and particularly of high-grade cancer.

PubMed

De Nunzio, Cosimo; Lombardo, Riccardo; Nacchia, Antonio; Tema, Giorgia; Tubaro, Andrea

2018-07-01

To analyse the impact of repeating a prostate-specific antigen (PSA) level assessment on prostate biopsy decision in a cohort of men undergoing prostate biopsy. From 2015 onwards, we consecutively enrolled, at a single institution in Italy, men undergoing 12-core transrectal ultrasonography-guided prostate needle biopsy. Indication for prostate biopsy was a PSA level of ≥4 ng/mL. Demographic, clinical, and histopathological data were collected. The PSA level was tested at enrolment (PSA 1 ) and 4 weeks later on the day before biopsy (PSA 2 ). Variations in PSA level were defined as: stable PSA 2 within a 10% variation, stable PSA 2 within a 20% variation, PSA 2 decreased by ≥10%, PSA 2 decreased by ≥20%, PSA 2 increased by ≥10%, PSA 2 increased by ≥20%, and PSA 2 <4 ng/mL. Percentages and multinomial logistic regression were used to analyse biopsy outcomes. High-grade cancer was defined as Grade group ≥3. Overall, 331 patients were enrolled. Prostate cancer was diagnosed in 153/331 (46%) patients and of them 80/153 (52%) had high-grade disease. When compared to the rest of the population, patients with a stable PSA within 20% variation had a higher risk of prostate cancer (odds ratio [OR] 1.80, P < 0.05) and high grade disease (OR 2.56, P < 0.05), patients with a PSA2 decreased by ≥20% had a lower risk of prostate cancer (OR 0.37, P < 0.05) and high grade disease (OR 0.13, P < 0.05), whilst patients with a PSA2 increased by ≥10% had an increased risk of high-grade prostate cancer (OR 1.93, P < 0.05). When PSA returned to normal values (<4 ng/mL) both risks of prostate cancer and high-grade disease were reduced (OR 0.33 and 0.01, respectively, P = 0.001). In a cohort of Italian men undergoing prostate biopsy, a reduction of ≥20% in PSA levels significantly reduced the risk of high-grade prostate cancer. Further multicentre studies should validate our present results. © 2018 The Authors BJU International © 2018 BJU International Published by John

Physicochemical and functional properties of dietary fiber from maca (Lepidium meyenii Walp.) liquor residue.

PubMed

Chen, Jinjin; Zhao, Qingsheng; Wang, Liwei; Zha, Shenghua; Zhang, Lijun; Zhao, Bing

2015-11-05

Using maca (Lepidium meyenii) liquor residue as the raw material, dietary fiber (DF) was prepared by chemical (MCDF) and enzymatic (MEDF) methods, respectively, of which the physicochemical and functional properties were comparatively studied. High contents of DF were found in MCDF (55.63%) and MEDF (81.10%). Both fibers showed good functional properties, including swelling capacity, water holding capacity, oil holding capacity, glucose adsorption capacity and glucose retardation index. MEDF showed better functional properties, which could be attributed to its higher content of DF, more irregular surface and more abundant monosaccharide composition. The results herein suggest that maca DF prepared by enzymatic method from liquor residue is a good functional ingredient in food products. Copyright © 2015 Elsevier Ltd. All rights reserved.

Analysis of macamides in samples of Maca (Lepidium meyenii) by HPLC-UV-MS/MS.

PubMed

McCollom, Megan M; Villinski, Jacquelyn R; McPhail, Kerry L; Craker, Lyle E; Gafner, Stefan

2005-01-01

The macamides are a distinct class of secondary metabolites that have so far been found only in Lepidium meyenii Walp. (Maca). Using HPLC-UV-MS/MS, the main macamides have been identified as n-benzylhexadecanamide, n-benzyl-(9Z)-octadecenamide, n-benzyl-(9Z, 12Z)-octadecadienamide, n-benzyl-(9Z, 12Z, 15Z)-octadecatrienamide and n-benzyloctadecanamide. The identities of n-benzyl-(9Z)-octadecenamide and n-benzyl-(9Z, 12Z)-octadecadienamide were confirmed by comparison of chromatographic and spectral properties with synthetic analogues. Total macamides have been quantified by HPLC-UV in plant material from different vendors using n-benzylhexadecanamide as an external standard. The amount of macamides in the dried plant material ranged from 0.0016 to 0.0123%.

Effect of three different cultivars of Lepidium meyenii (Maca) on learning and depression in ovariectomized mice

PubMed Central

Rubio, Julio; Caldas, Maria; Dávila, Sonia; Gasco, Manuel; Gonzales, Gustavo F

2006-01-01

Background Lepidium meyenii Walp. (Brassicaceae), known as Maca, is a Peruvian hypocotyl growing exclusively between 4000 and 4500 m altitude in the central Peruvian Andes, particularly in Junin plateau and is used traditionally to enhance fertility. Maca is a cultivated plant and different cultivars are described according to the color of the hypocotyls. Methods The study aimed to elucidate the effect of Yellow, Red and Black Maca on cognitive function and depression in ovariectomized (OVX) mice. In all experiments OVX mice were treated during 21 days and divided in four groups: control group, Yellow Maca, Red Maca and Black Maca. Latent learning was assessed using the water finding task and the antidepressant activity of the three varieties of Maca was evaluated using the forced swimming test. Animals were sacrificed at the end of each treatment and the uterus were excised and weighed. Results Black Maca was the variety that showed the best response in the water finding task, particularly in the trained mice. The three varieties were effective to reduce finding latency in non trained and trained mice (P < 0.05). In the force swimming test, all varieties assessed reduced the time of immobility and increased uterine weight in OVX mice. Conclusion Black Maca appeared to have more beneficial effects on latent learning in OVX mice; meanwhile, all varieties of Maca showed antidepressant activity. PMID:16796734

Effect of three different cultivars of Lepidium meyenii (Maca) on learning and depression in ovariectomized mice.

PubMed

Rubio, Julio; Caldas, Maria; Dávila, Sonia; Gasco, Manuel; Gonzales, Gustavo F

2006-06-23

Lepidium meyenii Walp. (Brassicaceae), known as Maca, is a Peruvian hypocotyl growing exclusively between 4000 and 4500 m altitude in the central Peruvian Andes, particularly in Junin plateau and is used traditionally to enhance fertility. Maca is a cultivated plant and different cultivars are described according to the color of the hypocotyls. The study aimed to elucidate the effect of Yellow, Red and Black Maca on cognitive function and depression in ovariectomized (OVX) mice. In all experiments OVX mice were treated during 21 days and divided in four groups: control group, Yellow Maca, Red Maca and Black Maca. Latent learning was assessed using the water finding task and the antidepressant activity of the three varieties of Maca was evaluated using the forced swimming test. Animals were sacrificed at the end of each treatment and the uterus were excised and weighed. Black Maca was the variety that showed the best response in the water finding task, particularly in the trained mice. The three varieties were effective to reduce finding latency in non trained and trained mice (P < 0.05). In the force swimming test, all varieties assessed reduced the time of immobility and increased uterine weight in OVX mice. Black Maca appeared to have more beneficial effects on latent learning in OVX mice; meanwhile, all varieties of Maca showed antidepressant activity.

Beneficial effects of Lepidium meyenii (Maca) on psychological symptoms and measures of sexual dysfunction in postmenopausal women are not related to estrogen or androgen content.

PubMed

Brooks, Nicole A; Wilcox, Gisela; Walker, Karen Z; Ashton, John F; Cox, Marc B; Stojanovska, Lily

2008-01-01

To examine the estrogenic and androgenic activity of Lepidium meyenii (Maca) and its effect on the hormonal profile and symptoms in postmenopausal women. Fourteen postmenopausal women completed a randomized, double-blind, placebo-controlled, crossover trial. They received 3.5 g/day of powered Maca for 6 weeks and matching placebo for 6 weeks, in either order, over a total of 12 weeks. At baseline and weeks 6 and 12 blood samples were collected for the measurement of estradiol, follicle-stimulating hormone, luteinizing hormone, and sex hormone-binding globulin, and the women completed the Greene Climacteric Scale to assess the severity of menopausal symptoms. In addition, aqueous and methanolic Maca extracts were tested for androgenic and estrogenic activity using a yeast-based hormone-dependent reporter assay. No differences were seen in serum concentrations of estradiol, follicle-stimulating hormone, luteinizing hormone, and sex hormone-binding globulin between baseline, Maca treatment, and placebo (P > 0.05). The Greene Climacteric Scale revealed a significant reduction in scores in the areas of psychological symptoms, including the subscales for anxiety and depression and sexual dysfunction after Maca consumption compared with both baseline and placebo (P < 0.05). These findings did not correlate with androgenic or alpha-estrogenic activity present in the Maca as no physiologically significant activity was observed in yeast-based assays employing up to 4 mg/mL Maca extract (equivalent to 200 mg/mL Maca). Preliminary findings show that Lepidium meyenii (Maca) (3.5 g/d) reduces psychological symptoms, including anxiety and depression, and lowers measures of sexual dysfunction in postmenopausal women independent of estrogenic and androgenic activity.

Effect of ethanol extract of Lepidium meyenii Walp. on osteoporosis in ovariectomized rat.

PubMed

Zhang, Yongzhong; Yu, Longjiang; Ao, Mingzhang; Jin, Wenwen

2006-04-21

Maca (Lepidium meyenii Walp.) is a cruciferous plant from the Andes of Peru. The root of Maca is traditionally employed for its supposed properties in aphrodisiacs and improving fertility, it also has been widely used to help alleviate the symptoms of menopause. The purpose of this study was to evaluate the effect of ethanol extract of Maca on postmenopausal osteoporosis in ovariectomized rats. Female Sprague-Dawley rats were divided into four groups: Sham-operated and ovariectomized groups were fed with equivolume of distilled water, and the remaining ovariectomized groups were orally administrated with ethanol extract of Maca at 0.096 and 0.24 g/kg for 28 weeks. The findings derived from the basis of bone mineral density, biomechanical, biochemical and histopathological parameters indicated that higher dose of ethanol extract of Maca was effective in the prevention of estrogen deficient bone loss.

[Determination of benzyl glucosinolate in Lepidium meyenii from different regions by HPLC].

PubMed

Tang, Lin; Yin, Hong-jun; Si, Cong-cong; Hu, Xiao-yan; Long, Zheng-hai

2015-12-01

The content of benzyl isothiocyanate (BITC) which as the enzymatic hydrolysis product of benzyl glucosinolate through thioglucosidase was determined by HPLC. The content of benzyl isothiocyanate (BITC) which as the enzymatic hydrolysis product of benzyl glucosinolate through thioglucosidase was determined by HPLC. The chromatography condition was as follows: Kaseisorb LC ODS 2000 (4.6 mm x 150 mm, 5 min) column with the mobile phase of acetonitrile(A)-water( B) under gradient elution (0-5 min, 3%-8% A; 5-9 min, 8%-48% A; 9-23 min, 48%-62% A; 23-28 min, 62%-99% A); the flow rate was 1.0 mL x min(-1) with 10 microL injection volume; detection wavelength was 246 nm and temperature of column was 40 degrees C. The content of benzyl glucosinolate was in the range of 10.76-17.91 g x L(-1). The method is simple, accurate and good reproducibility which can be used for the determination of benzyl glucosinolate in Lepidium meyenii, effectively.

P110β Inhibition Reduces Histone H3K4 Di-Methylation in Prostate Cancer.

PubMed

Pang, Jun; Yang, Yue-Wu; Huang, Yiling; Yang, Jun; Zhang, Hao; Chen, Ruibao; Dong, Liang; Huang, Yan; Wang, Dongying; Liu, Jihong; Li, Benyi

2017-02-01

Epigenetic alteration plays a major role in the development and progression of human cancers, including prostate cancer. Histones are the key factors in modulating gene accessibility to transcription factors and post-translational modification of the histone N-terminal tail including methylation is associated with either transcriptional activation (H3K4me2) or repression (H3K9me3). Furthermore, phosphoinositide 3-kinase (PI3 K) signaling and the androgen receptor (AR) are the key determinants in prostate cancer development and progression. We recently showed that prostate-targeted nano-micelles loaded with PI3 K/p110beta specific inhibitor TGX221 blocked prostate cancer growth in vitro and in vivo. Our objective of this study was to determine the role of PI3 K signaling in histone methylation in prostate cancer, with emphasis on histone H3K4 methylation. PI3 K non-specific inhibitor LY294002 and p110beta-specific inhibitor TGX221 were used to block PI3 K/p110beta signaling. The global levels of H3K4 and H3K9 methylation in prostate cancer cells and tissue specimens were evaluated by Western blot assay and immunohistochemical staining. A synthetic androgen R1881 was used to stimulate AR activity in prostate cancer cells. A castration-resistant prostate cancer (CRPC) specific human tissue microarray (TMA) was used to assess the global levels of H3K4me2 methylation by immunostaining approach. Our data revealed that H3K4me2 levels were significantly elevated after androgen stimulation. With RNA silencing and pharmacology approaches, we further defined that inhibition of PI3 K/p110beta activity through gene-specific knocking down and small chemical inhibitor TGX221 abolished androgen-stimulated H3K4me2 methylation. Consistently, prostate cancer-targeted delivery of TGX221 in vivo dramatically reduced the global levels of H3K4me2 as assessed by immunohistochemical staining on tissue section of mouse xenografts from CRPC cell lines 22RV1 and C4-2. Finally

Chronic baseline prostate inflammation is associated with lower tumor volume in men with prostate cancer on repeat biopsy: Results from the REDUCE study.

PubMed

Moreira, Daniel M; Nickel, J Curtis; Andriole, Gerald L; Castro-Santamaria, Ramiro; Freedland, Stephen J

2015-09-01

To evaluate whether baseline acute and chronic prostate inflammation among men with initial negative biopsy for prostate cancer (PC) is associated with PC volume at the 2-year repeat prostate biopsy in a clinical trial with systematic biopsies. Retrospective analysis of 886 men with negative baseline prostate biopsy and positive 2-year repeat biopsy in the Reduction by Dutasteride of PC Events (REDUCE) study. Acute and chronic inflammation and tumor volume were determined by central pathology. The association of baseline inflammation with 2-year repeat biopsy cancer volume was evaluated with linear and Poisson regressions controlling for demographics and laboratory variables. Chronic, acute inflammation, and both were detected in 531 (60%), 12 (1%), and 84 (9%) baseline biopsies, respectively. Acute and chronic inflammation were significantly associated with each other (P < 0.001). Chronic inflammation was associated with larger prostate (P < 0.001) and lower pre-repeat biopsy PSA (P = 0.01). At 2-year biopsy, baseline chronic inflammation was associated with lower mean tumor volume (2.07 µl vs. 3.15 µl; P = 0.001), number of biopsy cores involved (1.78 vs. 2.19; P < 0.001), percent of cores involved (17.8% vs. 22.8%; P < 0.001), core involvement (0.21 µl vs. 0.31 µl; P < 0.001), and overall percent tumor involvement (1.40% vs. 2.01%; P < 0.001). Results were unchanged in multivariable analysis. Baseline acute inflammation was not associated with any tumor volume measurement. In a cohort of men with 2-year repeat prostate biopsy positive for PC after a negative baseline biopsy, baseline chronic inflammation was associated with lower PC volume. © 2015 Wiley Periodicals, Inc.

Finasteride Concentrations and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial

PubMed Central

Till, Cathee; Goodman, Phyllis J.; Chen, Xiaohong; Leach, Robin J.; Johnson-Pais, Teresa L.; Hsing, Ann W.; Hoque, Ashraful; Tangen, Catherine M.; Chu, Lisa; Parnes, Howard L.; Schenk, Jeannette M.; Reichardt, Juergen K. V.; Thompson, Ian M.; Figg, William D.

2015-01-01

Objective In the Prostate Cancer Prevention Trial (PCPT), finasteride reduced the risk of prostate cancer by 25%, even though high-grade prostate cancer was more common in the finasteride group. However, it remains to be determined whether finasteride concentrations may affect prostate cancer risk. In this study, we examined the association between serum finasteride concentrations and the risk of prostate cancer in the treatment arm of the PCPT and determined factors involved in modifying drug concentrations. Methods Data for this nested case-control study are from the PCPT. Cases were drawn from men with biopsy-proven prostate cancer and matched controls. Finasteride concentrations were measured using a liquid chromatography-mass spectrometry validated assay. The association of serum finasteride concentrations with prostate cancer risk was determined by logistic regression. We also examine whether polymorphisms in the enzyme target and metabolism genes of finasteride are related to drug concentrations using linear regression. Results and Conclusions Among men with detectable finasteride concentrations, there was no association between finasteride concentrations and prostate cancer risk, low-grade or high-grade, when finasteride concentration was analyzed as a continuous variable or categorized by cutoff points. Since there was no concentration-dependent effect on prostate cancer, any exposure to finasteride intake may reduce prostate cancer risk. Of the twenty-seven SNPs assessed in the enzyme target and metabolism pathway, five SNPs in two genes, CYP3A4 (rs2242480; rs4646437; rs4986910), and CYP3A5 (rs15524; rs776746) were significantly associated with modifying finasteride concentrations. These results suggest that finasteride exposure may reduce prostate cancer risk and finasteride concentrations are affected by genetic variations in genes responsible for altering its metabolism pathway. Trial Registration ClinicalTrials.gov NCT00288106 PMID:25955319

Reduced plasma levels of coagulation factors in relation to prostate cancer.

PubMed

Beecken, Wolf-Dietrich; Bentas, Wassilios; Engels, Knut; Glienke, Wolfgang; Urbschat, Anja; Jonas, Dietger; Binder, Jochen; Scharrer, Inge

2002-10-01

Prostate cancer has historically been associated with coagulation abnormalities. This study was undertaken to investigate the prevalence of abnormalities of coagulation factors in patients with prostate cancer before and after radical prostatectomy (RP). Because coagulation factors have been shown to be involved in tumor angiogenesis, the vascular density of the prostate tumors was assessed. Plasma of 40 consecutive patients with histologically proven prostate cancer was investigated pre-RP and post-RP. The antigen level for antithrombin, plasminogen activator inhibitor-1, and heparin cofactor-II, and the plasma activity of antithrombin and plasminogen were determined by using immunologic and chromogenic assays. The values of these assays were compared with a group of 28 male, age-matched patients without any evidence of cancer and 18 patients with orthopedic interventions preoperatively and postoperatively. The vascular density of the prostate tumors was assessed by staining paraffin sections with an antibody to CD34. The median plasma antigen levels and/or activities of the investigated factors were below normal in the prostate cancer patients before RP. Furthermore, coagulation factors were significantly lower than in the age-matched control group and patients before and after orthopedic surgery. In prostate cancer patients, the median values of all investigated factors went up to normal levels within 2 weeks after RP, whereas postsurgical levels in orthopedic patients remained stable. No correlations to tumor parameters have been observed. We assume that the reduction of these coagulation factors is a principle concept in prostate cancer that needs further investigation. Copyright 2002 Wiley-Liss, Inc.

A panel of kallikrein markers can reduce unnecessary biopsy for prostate cancer: data from the European Randomized Study of Prostate Cancer Screening in Göteborg, Sweden

PubMed Central

Vickers, Andrew J; Cronin, Angel M; Aus, Gunnar; Pihl, Carl-Gustav; Becker, Charlotte; Pettersson, Kim; Scardino, Peter T; Hugosson, Jonas; Lilja, Hans

2008-01-01

Background Prostate-specific antigen (PSA) is widely used to detect prostate cancer. The low positive predictive value of elevated PSA results in large numbers of unnecessary prostate biopsies. We set out to determine whether a multivariable model including four kallikrein forms (total, free, and intact PSA, and human kallikrein 2 (hK2)) could predict prostate biopsy outcome in previously unscreened men with elevated total PSA. Methods The study cohort comprised 740 men in Göteborg, Sweden, undergoing biopsy during the first round of the European Randomized study of Screening for Prostate Cancer. We calculated the area-under-the-curve (AUC) for predicting prostate cancer at biopsy. AUCs for a model including age and PSA (the 'laboratory' model) and age, PSA and digital rectal exam (the 'clinical' model) were compared with those for models that also included additional kallikreins. Results Addition of free and intact PSA and hK2 improved AUC from 0.68 to 0.83 and from 0.72 to 0.84, for the laboratory and clinical models respectively. Using a 20% risk of prostate cancer as the threshold for biopsy would have reduced the number of biopsies by 424 (57%) and missed only 31 out of 152 low-grade and 3 out of 40 high-grade cancers. Conclusion Multiple kallikrein forms measured in blood can predict the result of biopsy in previously unscreened men with elevated PSA. A multivariable model can determine which men should be advised to undergo biopsy and which might be advised to continue screening, but defer biopsy until there was stronger evidence of malignancy. PMID:18611265

The in vitro biological activity of Lepidium meyenii extracts.

PubMed

Valentová, K; Buckiová, D; Kren, V; Peknicová, J; Ulrichová, J; Simánek, V

2006-03-01

The biological activity of methanolic and aqueous extracts from dehydrated hypocotyls of Lepidium meyenii (Brassicaceae, vernacular name "maca"), was studied on rat hepatocytes and human breast cancer MCF-7 cells. The extracts did not exhibit cytotoxicity in hepatocyte primary cultures up to 10 mg/ml as measured by the MTT viability test, and lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) leakage. Moreover, after 72 h, extracts inhibited LDH and AST leakage from the hepatocytes. When hepatocytes were intoxicated by t-butyl hydroperoxide, neither extract prevented oxidative damage. Both extracts showed weak antioxidant activity in the DPPH radical scavenging test with IC(50) values of 3.46 +/- 0.16 and 0.71 +/- 0.10 mg/ml, for aqueous and methanolic extracts, respectively. Thus, the observed effect on spontaneous enzyme leakage is probably mediated through mechanisms other than antioxidant activity. Both methanolic and aqueous extracts have shown estrogenic activity comparable with that of silymarin in MCF-7 cell line. Maca estrogenicity was exhibited in the range from 100 to 200 mug of extract per ml. The findings in the present study show that maca does not display in vitro hepatotoxicity. In contrast, a slight cytoprotective effect, probably not mediated by antioxidant capacity, was noted. Maca extracts exhibited estrogenic activity comparably to the effect of silymarin in MCF-7 cells.

PSCA expression is associated with favorable tumor features and reduced PSA recurrence in operated prostate cancer.

PubMed

Heinrich, Marie-Christine; Göbel, Cosima; Kluth, Martina; Bernreuther, Christian; Sauer, Charlotte; Schroeder, Cornelia; Möller-Koop, Christina; Hube-Magg, Claudia; Lebok, Patrick; Burandt, Eike; Sauter, Guido; Simon, Ronald; Huland, Hartwig; Graefen, Markus; Heinzer, Hans; Schlomm, Thorsten; Heumann, Asmus

2018-05-31

Prostate Stem Cell Antigen (PSCA) is frequently expressed in prostate cancer but its exact function is unclear. To clarify contradictory findings on the prognostic role of PSCA expression, a tissue microarray containing 13,665 prostate cancers was analyzed by immunohistochemistry. PSCA staining was absent in normal epithelial and stromal cells of the prostate. Membranous and cytoplasmic PSCA staining was seen in 53.7% of 9642 interpretable tumors. Staining was weak in 22.4%, moderate in 24.5% and strong in 6.8% of tumors. PSCA expression was associated with favorable pathological and clinical tumor features: Early pathological tumor stage (p < 0.0001), low Gleason grade (p < 0.0001), absence of lymph node metastasis (p < 0.0001), low pre-operative PSA level (p = 0.0118), negative surgical margin (p < 0.0001) and reduced PSA recurrence (p < 0.0001). PSCA expression was an independent predictor of prognosis in multivariate analysis (hazard ratio 0.84, p < 0.0001). The absence of statistical relationship to TMPRSS2:ERG fusion status, chromosomal deletion or high tumor cell proliferation argues against a major role of PSCA for regulation of cell cycle or genomic integrity. PSCA expression is linked to favorable prognosis. PSCA measurement is a candidate for inclusion in multi-parametric prognostic prostate cancer tests.

Effects on starch and amylolytic enzymes during Lepidium meyenii Walpers root storage.

PubMed

Rondán-Sanabria, Gerby Giovanna; Valcarcel-Yamani, Beatriz; Finardi-Filho, Flavio

2012-10-01

The high water content in maca (Lepidium meyenii W.) roots combined with the damage produced during or after harvest makes them vulnerable to attack by enzymes and microorganisms. Although starch degradation has been extensively studied, in maca roots there is a paucity of research regarding the starch reserves. In this paper, parameters of starch degradation are shown to be related to the action of amylolytic enzymes during storage at room temperature. Over the course of three weeks, the starch and protein content, soluble sugar, total amylolytic activity, and α- and β-amylase activity were measured. In addition, the integrity of starch granules was observed by scanning electron microscopy. Despite the evidence of dehydration, there were no significant differences (p ≤ 0.5) in the total starch content or in the activities of α- and β-amylase. After the third week the roots remained suitable for consumption. The results indicate a postharvest latency that can lead to sprout or to senescence, depending on the environmental conditions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Structural Characterization and Immunomodulatory Activity of a Novel Polysaccharide from Lepidium meyenii.

PubMed

Zhang, Mengmeng; Wang, Guang; Lai, Furao; Wu, Hui

2016-03-09

A novel polysaccharide named as MC-1 was isolated from the roots of Lepidium meyenii using a water extraction method. Structural characterization revealed that MC-1 had an average molecular weight of 11.3 kDa and consisted of arabinose (26.21%), mannose (11.81%), glucose (53.66%), and galactose (8.32%). The main linkage types of MC-1 were proven to be (1 → 5)-α-L-Ara, (1 → 3)-α-L-Man, (1 → 2,6)-α-L-Man, (1 → )-α-D-Glc, (1 → 4)-α-D-Glc, (1 → 6)-α-D-Glc and (1 → 6)-β-D-Gal by methylation analysis, periodate oxidation-Smith degradation and NMR analysis. The immunostimulating assay indicated that MC-1 could significantly enhance the pinocytic and phagocytic capacity and promote the NO, TNF-α, and IL-6 secretion of RAW 264.7 cells, involving toll-like receptor 2, complement receptor 3, and mannose receptor mainly. These results suggested the potential utilization of MC-1 as an attractive functional food supplement candidate for hypoimmunity population.

Structural Characterization and Antifatigue Effect In Vivo of Maca (Lepidium meyenii Walp) Polysaccharide.

PubMed

Tang, Weimin; Jin, Lu; Xie, Lianghua; Huang, Juqing; Wang, Nan; Chu, Bingquan; Dai, Xulin; Liu, Yu; Wang, Rui; Zhang, Ying

2017-03-01

Maca (Lepidium meyenii Walp) polysaccharides (MP) with purity of 99.2% were obtained to investigate their structural characteristics and antifatigue effect in vivo. The physicochemical properties of MP were analyzed through high-performance gel filtration chromatography, IR, monosaccharide composition, methylation, GC-MS, and NMR analyses. The antifatigue effect of MP was evaluated by using a mouse weight-loaded swimming model. MP is an acidic heteropolysaccharide with an average molecular weight (M w ) of 793.5 kDa. It is composed of D-GalA: D-Glc: L-Ara: D-Man: D-Gal: L-Rha = 35.07:29.98:16.98:13.01:4.21:0.75 (mol, %). The findings revealed that MP contained β-1,3-Galp(A), β-1,3-Glcp, and α-1, 3-Manp linked alternatingly to form a backbone (5:4:1). MP (above mid-dosage 50 mg/kg bw/d) could effectively elongate swimming durations and accelerate average swimming speeds (within the 1st 5 min) of mice (P < 0.05) and improve the serous biochemical parameters of mice. Compared with the control model, high-dosage (100 mg/kg bw/d) MP treatment could significantly enhance glutathione peroxidase and creatine kinase activities (P < 0.05) and decreased lactate dehydrogenase activity (P < 0.01). High-dosage MP could significantly reduce the levels of blood urea nitrogen, lactic acid, and malondialdehyde (P < 0.05). MP is an acidic polysaccharide with a high D-GalA content, which could be responsible for the antifatigue effect of maca. © 2017 Institute of Food Technologists®.

Anti-fatigue activity of polysaccharide fractions from Lepidium meyenii Walp. (maca).

PubMed

Li, Jing; Sun, Qingrui; Meng, Qingran; Wang, Lei; Xiong, Wentao; Zhang, Lianfu

2017-02-01

The two fractions of polysaccharide MPS-1 and MPS-2 were extracted from Lepidium meyenii Walp. (maca) by water, and purified using a DEAE-52 and a Sephadex G-100 column. The molecular weight (M W ) of MPS-1 was 7.6kDa, and the M W of MPS-2 was 6.7kDa. The MPS-1 was composed of xylose, arabinose, galactose and glucose, with the mole ratio 1:1.7:3.3:30.5; the MPS-2 was composed of arabinose, galactose and glucose, with the mole ratio 1:1.3:36.8. The IR spectrum implied that only α-pyranose existed in MPS-1, and both α-pyranose and β-pyranose existed in MPS-2. The anti-fatigue activities of MPS-1 and MPS-2 were measured by the forced swimming test, along with the determination of blood lactate (BLA), urea nitrogen (BUN), lactic dehydrogenase (LDH) activity and liver glycogen (LG). The results indicated that both MPS-1 and MPS-2 presented dose-dependently positive effects on the fatigue related parameters. Additionally, MPS-2 has a better anti-fatigue effect than MPS-1. Copyright © 2016 Elsevier B.V. All rights reserved.

Can Prostate Imaging Reporting and Data System Version 2 reduce unnecessary prostate biopsies in men with PSA levels of 4-10 ng/ml?

PubMed

Xu, Ning; Wu, Yu-Peng; Chen, Dong-Ning; Ke, Zhi-Bin; Cai, Hai; Wei, Yong; Zheng, Qing-Shui; Huang, Jin-Bei; Li, Xiao-Dong; Xue, Xue-Yi

2018-05-01

To explore the value of Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2) for predicting prostate biopsy results in patients with prostate specific antigen (PSA) levels of 4-10 ng/ml. We retrospectively reviewed multi-parameter magnetic resonance images from 528 patients with PSA levels of 4-10 ng/ml who underwent transrectal ultrasound-guided prostate biopsies between May 2015 and May 2017. Among them, 137 were diagnosed with prostate cancer (PCa), and we further subdivided them according to pathological results into the significant PCa (S-PCa) and insignificant significant PCa (Ins-PCa) groups (121 cases were defined by surgical pathological specimen and 16 by biopsy). Age, PSA, percent free PSA, PSA density (PSAD), prostate volume (PV), and PI-RADS score were collected. Logistic regression analysis was performed to determine predictors of pathological results. Receiver operating characteristic curves were constructed to analyze the diagnostic value of PI-RADS v2 in PCa. Multivariate analysis indicated that age, PV, percent free PSA, and PI-RADS score were independent predictors of biopsy findings, while only PI-RADS score was an independent predictor of S-PCa (P < 0.05). The areas under the receiver operating characteristic curve for diagnosing PCa with respect to age, PV, percent free PSA, and PI-RADS score were 0.570, 0.430, 0.589 and 0.836, respectively. The area under the curve for diagnosing S-PCa with respect to PI-RADS score was 0.732. A PI-RADS score of 3 was the best cutoff for predicting PCa, and 4 was the best cutoff for predicting S-PCa. Thus, 92.8% of patients with PI-RADS scores of 1-2 would have avoided biopsy, but at the cost of missing 2.2% of the potential PCa cases. Similarly, 83.82% of patients with a PI-RADS score ≤ 3 would have avoided biopsy, but at the cost of missing 3.3% of the potential S-PCa cases. PI-RADS v2 could be used to reduce unnecessary prostate biopsies in patients with PSA levels of 4-10 ng/ml.

Prostate Cancer Screening (PDQ®)—Patient Version

Cancer.gov

Prostate cancer screening may help detect prostate cancer, but remains controversial as it has not been shown to reduce deaths from prostate cancer. Learn more about prostate cancer screening, including the potential benefits and harms, in this expert-reviewed information summary.

Hyperglycemic condition during puberty increases collagen fibers deposition in the prostatic stroma and reduces MMP-2 activity.

PubMed

Santos, Sérgio Alexandre Alcantara Dos; Porto Amorim, Elaine Manoela; Ribeiro, Larissa Mayume; Rinaldi, Jaqueline Carvalho; Delella, Flávia Karina; Justulin, Luis Antonio; Felisbino, Sérgio Luis

2017-12-02

Puberty is an important period for the growth and maturation of the male reproductive system, and is also a critical window for endocrine or environmental interference. The physiological levels of circulating insulin and hyperglycemic control are important factors for a normal prostate growth. Hyperglycemia during puberty is reported to retard the growth of the prostate gland, with remarkable effects on the epithelial compartment. Here, we investigated the impact of hyperglycemia along with a simultaneous or late insulin replacement on the ventral prostate growth in rats during puberty, paying special attention to the deposition of collagen fibers and activities of gelatinase, matrix metalloproteinase-2 (MMP-2), and -9 (MMP-9). Hyperglycemia was induced by streptozotocin (STZ) administration in 40-day-old male Wistar rats. A subset of hyperglycemic rats underwent an early insulin replacement (three days after the STZ administration), and another subset underwent a late insulin replacement (twenty days after the STZ administration). Animals were euthanized at 60 and/or 80 days of age. The ventral prostatic lobe was processed for picrosirius red staining, type I and III collagen immunohistochemistry, and gelatin zymography. Hyperglycemic animals showed an increased area of collagen fibers in the prostate, which was composed both types of collagens. MMP-2 activity was significantly reduced in the hyperglycemic animals, while MMP-9 activity was very low and showed no alteration. The simultaneous and late insulin administration restored collagen content and MMP-2 activity. In conclusion, puberty is a critical window for prostate maturation and type-1 diabetes-induced hyperglycemia affects the ratio of the prostatic parenchymal and stromal growth, leading to fibrotic tissues by also MMP-2 down regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Prostatic Artery Embolization for Enlarged Prostates Due to Benign Prostatic Hyperplasia. How I Do It

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carnevale, Francisco C., E-mail: fcarnevale@uol.com.br; Antunes, Alberto A., E-mail: antunesuro@uol.com.br

2013-12-15

Prostatic artery embolization (PAE) has emerged as an alternative to surgical treatments for benign prostatic hyperplasia (BPH). Patient selection and refined technique are essential for good results. Urodynamic evaluation and magnetic resonance imaging are very important and technical limitations are related to elderly patients with tortuous and atherosclerotic vessels, anatomical variations, difficulty visualizing and catheterizing small diameter arteries feeding the prostate, and the potential risk of bladder and rectum ischemia. The use of small-diameter hydrophilic microcatheters is mandatory. Patients can be treated safely by PAE with low rates of side effects, reducing prostate volume with clinical symptoms and quality ofmore » life improvement without urinary incontinence, ejaculatory disorders, or erectile dysfunction. A multidisciplinary approach with urologists and interventional radiologists is essential to achieve better results.« less

Prophylactic antibiotics reduce sepsis after biopsy of the prostate.

PubMed

Hayatzaki, Khalilullah; Menne, Sveinar; Nielsen, Karsten

2014-11-01

Prostate cancer is the most common form of cancer in Danish men, and the incidence is rising. The diag-nosis is made by transrectal prostate biopsy guided by ultrasound. This procedure has several complications, the most severe being sepsis. In our department, this is sought prevented by administering the prophylactic antibiotics metronidazol and ciprofloxacin. This study examined the rate of sepsis in patients who had the procedure performed at our department. The electronic patient records of all patients who had transrectal ultrasound of the prostate with biopsies performed at the Department of Urology at Naestved Hospital in the period from 1 May 2009 to 31 May 2011 were examined, and all admissions to our department (or any department in the same region) due to sepsis within two weeks of the procedure were registered. A total of 438 patients had the procedure performed, some multiple times, which resulted in a total of 511 procedures. In all, four patients were later admitted due to sepsis, corresponding to 0.91%. Three of the patients had positive blood and urine cultures in which Escherichia coli resistant to ciprofloxacin were found, the last had been prescribed antibiotics by a general practitioner the previous day, and no bacteria could be cultured. The frequency of sepsis after transrectal needle biopsies from the prostate at our department was found to be below 1% in this study, which is comparable to international findings. Most of the cases of sepsis were related to ciprofloxacin-resistant bacteria. Further randomised studies are needed to investigate the ideal prophylactic regime. not relevant. not relevant.

N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells.

PubMed

Lee, John K; Phillips, John W; Smith, Bryan A; Park, Jung Wook; Stoyanova, Tanya; McCaffrey, Erin F; Baertsch, Robert; Sokolov, Artem; Meyerowitz, Justin G; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M; Shokat, Kevan M; Gustafson, W Clay; Huang, Jiaoti; Witte, Owen N

2016-04-11

MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance, and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

The effectiveness of reducing the daily dose of finasteride in men with benign prostatic hyperplasia

PubMed Central

Sullivan, Michael J; Geller, Jack

2002-01-01

Background Finasteride, a 5 alpha reductase inhibitor, is an established treatment for benign prostatic hyperplasia. The recommended dosage is 5 mg a day, however case reports have show effectiveness with lower doses. The objective of the current study was to determine in men with benign prostatic hyperplasia, previously treated for at least one year with finasteride 5 mg daily, if they will maintain subjective and objective improvements in urinary obstruction when treated with 2.5 mg of finasteride daily for one year. Methods In an open label, prospective study, 40 men with benign prostatic hyperplasia, previously treated for at least one year with 5 mg of finasteride, took 2.5 mg of finasteride daily for one year. Measurements included AUA symptom score, maximum flow rate, voided volume and PSA. Results There were no significant changes in maximum flow rate, voided volume, or AUA symptom score after one year of finasteride 2.5 mg daily therapy. PSA increased significantly, p < .01, after one year of finasteride 2.5 mg daily, 2.0 +1.4 ng/ml, when compared to finasteride 5 mg daily, 1.4+ 1.0 ng/ml. Conclusions The daily dose of finasteride can be reduced to 2.5 mg daily without significant effect on subjective and objective measures of urinary obstruction. Although statistically significant increases in PSA are noted when reducing the daily finasteride dose from 5 mg to 2.5 mg, the clinical significance of a mean .6 ng/ml increase in PSA is questionable. PMID:11818031

Prostate Health Index improves multivariable risk prediction of aggressive prostate cancer.

PubMed

Loeb, Stacy; Shin, Sanghyuk S; Broyles, Dennis L; Wei, John T; Sanda, Martin; Klee, George; Partin, Alan W; Sokoll, Lori; Chan, Daniel W; Bangma, Chris H; van Schaik, Ron H N; Slawin, Kevin M; Marks, Leonard S; Catalona, William J

2017-07-01

To examine the use of the Prostate Health Index (PHI) as a continuous variable in multivariable risk assessment for aggressive prostate cancer in a large multicentre US study. The study population included 728 men, with prostate-specific antigen (PSA) levels of 2-10 ng/mL and a negative digital rectal examination, enrolled in a prospective, multi-site early detection trial. The primary endpoint was aggressive prostate cancer, defined as biopsy Gleason score ≥7. First, we evaluated whether the addition of PHI improves the performance of currently available risk calculators (the Prostate Cancer Prevention Trial [PCPT] and European Randomised Study of Screening for Prostate Cancer [ERSPC] risk calculators). We also designed and internally validated a new PHI-based multivariable predictive model, and created a nomogram. Of 728 men undergoing biopsy, 118 (16.2%) had aggressive prostate cancer. The PHI predicted the risk of aggressive prostate cancer across the spectrum of values. Adding PHI significantly improved the predictive accuracy of the PCPT and ERSPC risk calculators for aggressive disease. A new model was created using age, previous biopsy, prostate volume, PSA and PHI, with an area under the curve of 0.746. The bootstrap-corrected model showed good calibration with observed risk for aggressive prostate cancer and had net benefit on decision-curve analysis. Using PHI as part of multivariable risk assessment leads to a significant improvement in the detection of aggressive prostate cancer, potentially reducing harms from unnecessary prostate biopsy and overdiagnosis. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

NPM1 Silencing Reduces Tumour Growth and MAPK Signalling in Prostate Cancer Cells

PubMed Central

Loubeau, Gaëlle; Boudra, Rafik; Maquaire, Sabrina; Lours-Calet, Corinne; Beaudoin, Claude; Verrelle, Pierre; Morel, Laurent

2014-01-01

The chaperone nucleophosmin (NPM1) is over-expressed in the epithelial compartment of prostate tumours compared to adjacent healthy epithelium and may represent one of the key actors that support the neoplastic phenotype of prostate adenocarcinoma cells. Yet, the mechanisms that underlie NPM1 mediated phenotype remain elusive in the prostate. To better understand NPM1 functions in prostate cancer cells, we sought to characterize its impact on prostate cancer cells behaviour and decipher the mechanisms by which it may act. Here we show that NPM1 favors prostate tumour cell migration, invasion and colony forming. Furthermore, knockdown of NPM1 leads to a decrease in the growth of LNCaP-derived tumours grafted in Nude mice in vivo. Such oncogenic-like properties are found in conjunction with a positive regulation of NPM1 on the ERK1/2 (Extracellular signal-Regulated Kinases 1/2) kinase phosphorylation in response to EGF (Epidermal Growth Factor) stimulus, which is critical for prostate cancer progression following the setting of an autonomous production of the growth factor. NPM1 could then be a target to switch off specifically ERK1/2 pathway activation in order to decrease or inhibit cancer cell growth and migration. PMID:24796332

Prostate Cancer Screening (PDQ®)—Health Professional Version

Cancer.gov

Prostate cancer screening with the prostate-specific antigen (PSA) test or digital rectal exams has not been shown to reduce prostate cancer deaths. Get detailed information about prostate cancer screening, including potential benefits and harms, in this summary for clinicians.

[Bacterial prostatitis and prostatic fibrosis: modern view on the treatment and prophylaxis].

PubMed

Zaitsev, A V; Pushkar, D Yu; Khodyreva, L A; Dudareva, A A

2016-08-01

Treatments of chronic bacterial prostatitis (CP) remain difficult problem. Bacterial prostatitis is a disease entity diagnosed clinically and by evidence of inflammation and infection localized to the prostate. Risk factors for UTI in men include urological interventions, such as transrectal prostate biopsy. Ensuing infections after prostate biopsy, such as UTI and bacterial prostatitis, are increasing due to increasing rates of fluoroquinolone resistance. The increasing global antibiotic resistance also significantly affects management of UTI in men, and therefore calls for alternative strategies. Prostatic inflammation has been suggested to contribute to the etiology of lower urinary tract symptoms (LUTS) by inducing fibrosis. Several studies have shown that prostatic fibrosis is strongly associated with impaired urethral function and LUTS severity. Fibrosis resulting from excessive deposition of collagen is traditionally recognized as a progressive irreversible condition and an end stage of inflammatory diseases; however, there is compelling evidence in both animal and human studies to support that the development of fibrosis could potentially be a reversible process. Prostate inflammation may induce fibrotic changes in periurethral prostatic tissues, promote urethral stiffness and LUTS. Patients experiencing CP and prostate-related LUTS could benefit from anti-inflammatory therapies, especially used in combination with the currently prescribed enzyme treatment with Longidase. Treatment results showed that longidase is highly effective in bacterial and abacterial CP. Longidase addition to standard therapeutic methods significantly reduced the disease symptoms and regression of inflammatory-proliferative alterations in the prostate.

Chrysophanic acid reduces testosterone-induced benign prostatic hyperplasia in rats by suppressing 5α-reductase and extracellular signal-regulated kinase

PubMed Central

Kim, Hye-Lin; Jung, Yunu; Kang, JongWook; Jeong, Mi-Young; Sethi, Gautam; Ahn, Kwang Seok; Um, Jae-Young

2017-01-01

Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases in male population, of which incidence increases gradually with age. In this study, we investigated the effect of chrysophanic acid (CA) on BPH. BPH was induced by a 4-week injection of testosterone propionate (TP). Four weeks of further injection with vehicle, TP, TP + CA, TP + finasteride was carried on. In the CA treatment group, the prostate weight was reduced and the TP-induced histological changes were restored as the normal control group. CA treatment suppressed the TP-elevated prostate specific antigen (PSA) expression. In addition, 5α-reductase, a crucial factor in BPH development, was suppressed to the normal level close to the control group by CA treatment. The elevated expressions of androgen receptor (AR), estrogen receptor α and steroid receptor coactivator 1 by TP administration were also inhibited in the CA group when compared to the TP-induced BPH group. Then we evaluated the changes in three major factors of the mitogen-activated protein kinase chain during prostatic hyperplasia; extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38). While ERK was elevated in the process of BPH, JNK and p38 was not changed. This up-regulated ERK was also reduced as normal by CA treatment. Further in vitro studies with RWPE-1 cells confirmed TP-induced proliferation and elevated AR, PSA and p-ERK were all reduced by CA treatment. Overall, these results suggest a potential pharmaceutical feature of CA in the treatment of BPH. PMID:27880726

Prostate-specific antigen increase during dutasteride to indicate the need for prostate biopsy: influence of prostatic inflammation.

PubMed

Sciarra, Alessandro; Maggi, Martina; Fasulo, Andrea; Salciccia, Stefano; Gentile, Vincenzo; Cattarino, Susanna; Gentilucci, Alessandro

2017-08-01

The aim of this study was to analyze the significance of an increase in total prostate-specific antigen (PSA) serum levels despite dutasteride treatment as a predictor of prostate cancer (PC) at biopsy. We focused our attention on the rate of the first PSA increase and on the influence of prostatic inflammation. From 2011 to 2016, 365 men with a previous negative prostate biopsy and persistent elevated PSA levels received dutasteride treatment. The population was followed for a range of 12-48 months. One hundred twelve cases with a confirmed PSA increase >0.5 ng/ml over the nadir value during the follow-up were included in Group A and underwent a new prostate biopsy. In Group A, the PSA increase was associated with PC at the re-biopsy in 66% of cases. The percentage of PSA reduction after 6 months of treatment was not a significant indicator of the risk for PC. The distribution of inflammatory infiltrates significantly (p<00.01) varied from positive to negative prostate biopsies. The relative risk for PC at biopsy significantly increased according to PSA level during dutasteride. Treatment with dutasteride can help to analyze PSA kinetic. A persistent prostatic inflammation is a factor able to reduce the performance of PSA kinetic during dutasteride treatment.

Smoking Is Associated with Acute and Chronic Prostatic Inflammation: Results from the REDUCE Study.

PubMed

Moreira, Daniel M; Nickel, J Curtis; Gerber, Leah; Muller, Roberto L; Andriole, Gerald L; Castro-Santamaria, Ramiro; Freedland, Stephen J

2015-04-01

Both anti- and proinflammatory effects of cigarette smoking have been described. As prostate inflammation is common, we hypothesized smoking could contribute to prostate inflammation. Thus, we evaluated the association of smoking status with acute and chronic inflammation within the prostate of men undergoing prostate biopsy. We retrospectively analyzed 8,190 men ages 50 to 75 years with PSA levels between 2.5 and 10 ng/mL enrolled in the Reduction by Dutasteride of Prostate Cancer Events study. Smoking status was self-defined as never, former, or current. Prostate inflammation was assessed by systematic central review blinded to smoking status. The association of smoking with inflammation in the baseline, 2-year, and 4-year biopsies was evaluated with univariable and multivariable logistic regressions. At study enrollment, 1,233 (15%), 3,203 (39%), and 3,754 (46%) men were current, former, and never smokers, respectively. Current smokers were significantly younger and had smaller prostates than former and never smokers (all P < 0.05). Former smokers were significantly heavier than current and never smokers (P < 0.001). Acute and chronic prostate inflammations were identified in 1,261 (15%) and 6,352 (78%) baseline biopsies, respectively. In univariable analysis, current smokers were more likely to have acute inflammation than former (OR, 1.35; P, 0.001) and never smokers (OR, 1.36; P, 0.001). The results were unchanged at 2- and 4-year biopsies. In contrast, current smoking was linked with chronic inflammation in the baseline biopsy, but not at 2- and 4-year biopsies. In conclusion, among men undergoing prostate biopsy, current smoking was independently associated with acute and possibly chronic prostate inflammations. ©2015 American Association for Cancer Research.

Survival in prostate cancer prevention trial detailed

Cancer.gov

In the NCI-sponsored Prostate Cancer Prevention Trial, initial findings from a decade ago showed that the drug finasteride significantly reduced the risk of prostate cancer, but among those who did develop prostate cancer, paradoxically, the drug was asso

Aerial parts of maca (Lepidium meyenii Walp.) as functional vegetables with gastrointestinal prokinetic efficacy in vivo.

PubMed

Jin, Wenwen; Chen, Xuemin; Huo, Qing; Cui, Yajie; Yu, Zejun; Yu, Longjiang

2018-06-20

Lepidium meyenii Walp. (maca) has been utilized in the Andean region because of its edibleness and medicinal value. The aerial parts of maca (APM) were analyzed for protein, total sugar, vitamins, amino acids, and minerals and its characteristic active ingredients at five different growth stages. The results showed the high protein, total sugar, vitamin C, niacin, potassium, and calcium contents of APM. All 17 amino acids and the characteristic active ingredients, namely, macamide, glucosinolates, adenosine, and total saponins, were detected. We examined the effects of maca plant powders on gastric emptying and intestinal propulsion and the levels of serum motilin and gastrin in atropine-treated mice. Benzyl isothiocyanate (BITC) was investigated to identify the potential active material in APM. The results revealed that both maca plant powders and BITC can promote the gastrointestinal prokinetic efficacy. Thus, APM feature potential as new functional vegetable sources.

Antioxidant and neuroprotector effect of Lepidium meyenii (maca) methanol leaf extract against 6-hydroxy dopamine (6-OHDA)-induced toxicity in PC12 cells.

PubMed

Rodríguez-Huamán, Ángel; Casimiro-Gonzales, Sandra; Chávez-Pérez, Jorge Antonio; Gonzales-Arimborgo, Carla; Cisneros-Fernández, Richard; Aguilar-Mendoza, Luis Ángel; Gonzales, Gustavo F

2017-05-01

Reactive oxygen species (ROS) are normally produced during cell metabolism, there is strong evidence to suggest that ROS produced in excess impair the cell and may be etiologically related to various neurodegenerative diseases. This study was undertaken to examine the effects of Lepidium meyenii (MACA) methanol leaf extract on neurotoxicity in PC12 cell exposed to 6-hydroxydopamine (6-OHDA). Fresh samples of "maca" leaves were processed in order to obtain foliar extracts and to evaluate the neurobiological activity on PC12 cells, subjected to the cytotoxic effect of 6-OHDA through the determination of the capacity antioxidant, cell viability and cytotoxicity assays on PC12 cells. The results of the tests of antioxidant activity, showed maximum values of 2262.37 and 1305.36 expressed in Trolox equivalents (TEAC), for the methanolic and aqueous fractions respectively. Cell viability assays at a dose of 10 μg extract showed an increase of 31% and 60% at 6 and 12 h of pretreatment, respectively. Cytotoxicity assays at the same dose and exposure time showed a 31.4% and 47.8% reduction in lactate dehydrogenase (LDH) activity and an increase in superoxide dismutase (SOD) activity. The results allow us to affirm that the methanolic foliar extract of "maca" presents in vitro neurobiological activity of antioxidant protection, increase in cell viability and reduction of cytotoxicity against oxidative stress generated by 6-OHDA. In conclusion, the present study shows a protective role for Lepidium meyenii leaf extract on 6-OHDA-induced toxicity by an antioxidant effect.

Identification of maca (Lepidium meyenii Walp.) and its adulterants by a DNA-barcoding approach based on the ITS sequence.

PubMed

Chen, Jin-Jin; Zhao, Qing-Sheng; Liu, Yi-Lan; Zha, Sheng-Hua; Zhao, Bing

2015-09-01

Maca (Lepidium meyenii) is an herbaceous plant that grows in high plateaus and has been used as both food and folk medicine for centuries because of its benefits to human health. In the present study, ITS (internal transcribed spacer) sequences of forty-three maca samples, collected from different regions or vendors, were amplified and analyzed. The ITS sequences of nineteen potential adulterants of maca were also collected and analyzed. The results indicated that the ITS sequence of maca was consistent in all samples and unique when compared with its adulterants. Therefore, this DNA-barcoding approach based on the ITS sequence can be used for the molecular identification of maca and its adulterants. Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Unripe Rubus coreanus Miquel suppresses migration and invasion of human prostate cancer cells by reducing matrix metalloproteinase expression.

PubMed

Kim, Yesl; Lee, Seung Min; Kim, Jung-Hyun

2014-01-01

Rubus coreanus Miquel (RCM) is used to promote prostate health and has been shown to have anti-oxidant and anti-carcinogenic activities. However, the effects and mechanisms of RCM on prostate cancer metastasis remain unclear. PC-3 and DU 145 cells were treated with ethanol or water extract of unripe or ripe RCM and examined for cell invasion, migration, and matrix metalloproteinases (MMPs) activity and expression. Phosphoinositide 3-kinase (PI3K) and Akt activities were examined. Unripe RCM extracts exerted significant inhibitory effects on cell migration, invasion, and MMPs activities. A significant reduction in MMPs activities by unripe RCM ethanol extract treatment (UE) was associated with reduction of MMPs expression and induction of tissue inhibitors of metalloproteinases (TIMPs) expression. Furthermore, PI3K/Akt activity was diminished by UE treatment. In this study, we demonstrated that UE decreased metastatic potential of prostate cancer cells by reducing MMPs expression through the suppression of PI3K/Akt phosphorylation, thereby decreasing MMP activity and enhancing TIMPs expression.

A novel approach for evaluation of prostate deformation and associated dosimetric implications in IGRT of the prostate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayyas, Essa, E-mail: emayyas1@hfhs.org, E-mail: ortonc@comcast.net; Kim, Jinkoo; Kumar, Sanath

2014-09-15

Purpose: Prostate deformation is assumed to be a secondary correction and is typically ignored in the planning target volume (PTV) margin calculations. This assumption needs to be tested, especially when planning margins are reduced with daily image-guidance. In this study, deformation characteristics of the prostate and seminal vesicles were determined, and the dosimetric impact on treatment plans with different PTV margins was investigated. Methods: Ten prostate cancer patients were retrospectively selected for the study, each with three fiducial markers implanted in the prostate. Two hundred CBCT images were registered to respective planning CT images using a B-spline-based deformable image registrationmore » (DIR) software. A manual bony anatomy-based match was first applied based on the alignment of the pelvic bones and fiducial landmarks. DIR was then performed. For each registration, deformation vector fields (DVFs) of the prostate and seminal vesicles (SVs) were quantified using deformation-volume histograms. In addition, prostate rotation was evaluated and compared with prostate deformation. For a patient demonstrating small and large prostate deformations, target coverage degradation was analyzed in each of three treatment plans with PTV margins of 10 mm (6 mm at the prostate/rectum interface), as well as 5, and 3 mm uniformly. Results: Deformation of the prostate was most significant in the anterior direction. Maximum prostate deformation of greater than 10, 5, and 3 mm occurred in 1%, 17%, and 76% of the cases, respectively. Based on DVF-histograms, DVF magnitudes greater than 5 and 3 mm occurred in 2% and 27% of the cases, respectively. Deformation of the SVs was most significant in the posterior direction, and it was greater than 5 and 3 mm in 7.5% and 44.9% of the cases, respectively. Prostate deformation was found to be poorly correlated with rotation. Fifty percent of the cases showed rotation with negligible deformation and 7% of the cases

Structure analysis and anti-fatigue activity of a polysaccharide from Lepidium meyenii Walp.

PubMed

Tang, Yun; Zhu, Zhen-Yuan; Pan, Li-Chao; Sun, Huiqing; Song, Qiao-Ying; Zhang, Yongmin

2018-03-16

A polysaccharide was obtained from Lepidium meyenii Walp by hot water extraction and purification by Millipore (100 kD) and Sephadex G-200. The content of polysaccharide was examined to be 89.9% with phenol-sulfuric acid method. Its average molecular weight was estimated to be 2.213 × 10 6  Da by High Performance Gel Permeation Chromatography (HPGPC). Monosaccharide analysis showed that the polysaccharide was composed of arabinose, mannose, glucose and galactose with the molar ratio of 2.134: 1: 2.78: 2.82. After Smith degradation, methylation, infrared spectroscopy and NMR, the primary structure of the polysaccharide was identified. The backbone of the polysaccharide was composed of →4)-β-D-Galp-(1→ and →4)-α-D-Galp-(1→, while the branches were comprised of →6)-β-D-Glup-(1→, →5)- β-D-Araf-(1→, →3,6)-α-D-Manp-(1→, →3)-α-D-Galp-(1→, and α-D-Glup-(1→. The anti-fatigue effect of the polysaccharide was evaluated using exhaustive swimming test and biochemical indexes. The results indicated the polysaccharide has anti-fatigue effect.

Macrocyclic peptides decrease c-Myc protein levels and reduce prostate cancer cell growth.

PubMed

Mukhopadhyay, Archana; Hanold, Laura E; Thayele Purayil, Hamsa; Gisemba, Solomon A; Senadheera, Sanjeewa N; Aldrich, Jane V

2017-08-03

The oncoprotein c-Myc is often overexpressed in cancer cells, and the stability of this protein has major significance in deciding the fate of a cell. Thus, targeting c-Myc levels is an attractive approach for developing therapeutic agents for cancer treatment. In this study, we report the anti-cancer activity of the macrocyclic peptides [D-Trp]CJ-15,208 (cyclo[Phe-D-Pro-Phe-D-Trp]) and the natural product CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]). [D-Trp]CJ-15,208 reduced c-Myc protein levels in prostate cancer cells and decreased cell proliferation with IC 50 values ranging from 2.0 to 16 µM in multiple PC cell lines. [D-Trp]CJ-15,208 induced early and late apoptosis in PC-3 cells following 48 hours treatment, and growth arrest in the G2 cell cycle phase following both 24 and 48 hours treatment. Down regulation of c-Myc in PC-3 cells resulted in loss of sensitivity to [D-Trp]CJ-15,208 treatment, while overexpression of c-Myc in HEK-293 cells imparted sensitivity of these cells to [D-Trp]CJ-15,208 treatment. This macrocyclic tetrapeptide also regulated PP2A by reducing the levels of its phosphorylated form which regulates the stability of cellular c-Myc protein. Thus [D-Trp]CJ-15,208 represents a new lead compound for the potential development of an effective treatment of prostate cancer.

Does Prostate Size Predict the Development of Incident Lower Urinary Tract Symptoms in Men with Mild to No Current Symptoms? Results from the REDUCE Trial.

PubMed

Simon, Ross M; Howard, Lauren E; Moreira, Daniel M; Roehrborn, Claus; Vidal, Adriana C; Castro-Santamaria, Ramiro; Freedland, Stephen J

2016-05-01

It has been shown that increased prostate size is a risk factor for lower urinary tract symptom (LUTS) progression in men who currently have LUTS presumed due to benign prostatic hyperplasia (BPH). To determine if prostate size is a risk factor for incident LUTS in men with mild to no symptoms. We conducted a post hoc analysis of the REDUCE study, which contained a substantial number of men (n=3090) with mild to no LUTS (International Prostate Symptom Score [IPSS] <8). Our primary outcome was determination of the effect of prostate size on incident LUTS presumed due to BPH defined as two consecutive IPSS values >14, or receiving any medical (α-blockers) or surgical treatment for BPH throughout the study course. To determine the risk of developing incident LUTS, we used univariable and multivariable Cox models, as well as Kaplan-Meier curves and the log-rank test. Among men treated with placebo during the REDUCE study, those with a prostate size of 40.1-80ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23-2.26, p=0.001) of developing incident LUTS compared to men with a prostate size 40.0ml or smaller. There was no association between prostate size and risk of incident LUTS in men treated with 0.5mg of dutasteride. The post hoc nature of our study design is a potential limitation. Men with mild to no LUTS but increased prostate size are at higher risk of incident LUTS presumed due to BPH. This association was negated by dutasteride treatment. Benign prostatic hyperplasia (BPH) is a very common problem among older men, which often manifests as lower urinary tract symptoms (LUTS), and can lead to potentially serious side effects. In our study we determined that men with mild to no current LUTS but increased prostate size are much more likely to develop LUTS presumed due to BPH in the future. This association was not seen in men treated with dutasteride, a drug approved for treatment of BPH. Our study reveals that men with a prostate size of 40

Resveratrol reduces the levels of circulating androgen precursors but has no effect on, testosterone, dihydrotestosterone, PSA levels or prostate volume. A 4-month randomised trial in middle-aged men.

PubMed

Kjaer, Thomas Nordstrøm; Ornstrup, Marie Juul; Poulsen, Morten Møller; Jørgensen, Jens Otto Lunde; Hougaard, David Michael; Cohen, Arieh Sierra; Neghabat, Shadman; Richelsen, Bjørn; Pedersen, Steen Bønløkke

2015-09-01

Resveratrol is a naturally occurring polyphenol with purported inhibitory effects on prostate growth and cancer development. A number of studies have demonstrated that resveratrol reduces prostate growth in animal models and reduces prostate cell growth in vitro. Based on these pre-clinical findings, interest in resveratrol is increasing in relation to the management of benign prostate hyperplasia (BPH) and prostate cancer. So far, no human trials have evaluated the effects of resveratrol on circulating androgens, prostate size, or biochemical markers of prostate size. In a randomized placebo controlled clinical study using two doses of resveratrol (150 mg or 1,000 mg resveratrol daily) for 4 months, we evaluated the effects on prostate size, prostate specific antigen (PSA) and sex steroid hormones in 66 middle-aged men suffering from the metabolic syndrome(MetS). At baseline, prostate size and PSA were positively correlated (R = 0.34, P < 0.007) as was prostate size and age (R = 0.37, P < 0.003). Prostate size did not correlate with testosterone, free testosterone, dihydrotestosterone (DHT), or any other androgen precursor at baseline. The highest dose of resveratrol lowered the serum level of androstenedione 24% (P = 0.052), dehydroepiandrosterone (DHEA) 41% (P < 0.01), and dehydroepiandrosterone-sulphate (DHEAS) 50% (p<0.001), compared to the control group. However, prostate size and levels of PSA, testosterone, free testosterone and DHT remained unchanged. In this population of middle-aged men suffering from MetS, high dose resveratrol (1,000 mg daily) administration for 4 months significantly lowered serum levels of the androgen precursors androstenedione, DHEA and DHEAS, whereas prostate size and circulating levels of PSA, testosterone, free testosterone, and dihydrotestosterone were unaffected. The present study suggests that resveratrol does not affect prostate volume in healthy middle-aged men as measured by PSA levels and CT acquired prostate volumes

The Stockholm-3 (STHLM3) Model can Improve Prostate Cancer Diagnostics in Men Aged 50-69 yr Compared with Current Prostate Cancer Testing.

PubMed

Eklund, Martin; Nordström, Tobias; Aly, Markus; Adolfsson, Jan; Wiklund, Peter; Brandberg, Yvonne; Thompson, James; Wiklund, Fredrik; Lindberg, Johan; Presti, Joseph C; StLezin, Mark; Clements, Mark; Egevad, Lars; Grönberg, Henrik

2016-11-23

Prostate cancer screening is associated with low specificity, unnecessary biopsies, and overdiagnosis. We have previously shown that the Stockholm-3 model (S3M) can reduce biopsies compared with using prostate-specific antigen (PSA) ≥3ng/ml as an indication for biopsy. Urologists in today's current prostate cancer testing (CPT) have access to numerous variables in addition to PSA (eg, age, ethnicity, family history, free PSA, PSA velocity, digital rectal examination, and prostate volume) to support biopsy decisions. We estimated the number of prostate cancers diagnosed and prostate biopsies performed if S3M replaced CPT in Stockholm, Sweden, by comparing biopsy results in 56 282 men who underwent PSA testing according to CPT in Stockholm in 2011 with the 47 688 men enrolled in the STHLM3 validation cohort 2012-2015. With the same sensitivity as CPT to diagnose Gleason score ≥7 prostate cancer, S3M was estimated to reduce the number of men biopsied by 53% (95% confidence interval [CI]: 41-65%), avoid 76% (95% CI: 67-81%) of negative biopsies, and reduce Gleason score 6 cancers by 23% (95% CI: 6-40%). S3M has the potential to improve prostate cancer diagnostics by better selecting men with high risk of GS ≥7 prostate cancer. We modeled the effect the Stockholm-3 model would have on prostate cancer diagnostics if it replaced current clinical practice. We found that Stockholm-3 model may substantially reduce the number of biopsies, while maintaining the same sensitivity to diagnose clinically significant prostate cancer. Copyright © 2016. Published by Elsevier B.V.

Flaxseed suppressed prostatic epithelial proliferation in a rat model of benign prostatic hyperplasia.

PubMed

Said, Mahmoud M; Hassan, Nahla S; Schlicht, Michael J; Bosland, Maarten C

2015-01-01

Benign prostatic hyperplasia (BPH), a disease occurring frequently among elderly males, is a slow progressive enlargement of the fibromuscular and epithelial structures of the prostate gland. Dietary factors may influence the prostate and exert an influence on prostatic growth and disease. The current study was undertaken to investigate the protective effect of dietary flaxseed supplementation against testosterone-induced prostatic hyperplasia in male rats. Forty male Wistar rats were divided into 5 groups: (1) untreated control; (2) treatment with testosterone propionate (TP) to induce prostate enlargement; (3) TP-treated group fed a diet containing 5% milled flaxseed; (4) TP-treated group fed a diet containing 10% milled flaxseed; and (5) TP-treated group fed a diet containing 20 ppm finasteride. Treatment with TP significantly increased the absolute and relative weights of different prostatic lobes, serum testosterone (T), and testosterone/estradiol ratio, as well as prostatic vascular endothelial growth factor (VEGF) expression, RNA synthesis per cell, and epithelial cell proliferation, detected as Ki67 labeling. Histopathological examination did not reveal marked differences in acinar morphology in ventral prostate, whereas morphometric analysis showed significantly increased epithelial cell height. Co-administration of flaxseed or finasteride with TP significantly reduced prostatic VEFG, epithelial cell proliferation, and RNA/DNA ratio, along with a significant increase in serum T and testosterone/estradiol ratio compared with TP-only-treated rats. Our results indicate that flaxseed, similar to the 5α-reductase inhibitor finasteride, blocked TP-induced prostate enlargement in a rat model of BPH, likely through suppression of prostatic VEFG and cellular proliferation.

[Assesing the effect of Lepidium meyenii "Maca" on the gastric mucosa in patients with functional dyspepsia].

PubMed

Benites Goñi, Harold Eduardo; Cok García, Jaime; Bussalleu Cavero, Alejandra; Bustamente Robles, Katherine Yelenia; Zegarra Chang, Arturo; Bravo, Eduar; Bussalleu Rivera, Alejandro

2014-01-01

The present study was designed to determine the histological effect of Lepidium meyenii "Maca" on the gastric mucosa in patients with functional dyspepsia. This study consists of a clinical case series, in which the effect of Maca on the gastric histopathology of 29 Peruvian patients diagnosed with functional dyspepsia was examined. The presence of H. pylori, as well as the degree and depth of the gastric mucosa inflammation was evaluated from biopsies obtained before and after the treatment based solely of Maca 3 grams per day for four weeks. Average values of the degree and depth of mucosal inflammation before and after the treatment were compared showing no statistical difference among the samples. Sixteen patients were infected with H. pylori, and they remained infected after the treatment with Maca. A four week long treatment with Maca does not produce significant changes on gastric mucosa of patients with functional dyspepsia, neither on H. pylori eradication.

SULT2B1b Sulfotransferase: Induction by Vitamin D Receptor and Reduced Expression in Prostate Cancer

PubMed Central

Seo, Young-Kyo; Mirkheshti, Nooshin; Song, Chung S.; Kim, Soyoung; Dodds, Sherry; Ahn, Soon C.; Christy, Barbara; Mendez-Meza, Rosario; Ittmann, Michael M.; Abboud-Werner, Sherry

2013-01-01

An elevated tumor tissue androgen level, which reactivates androgen receptor in recurrent prostate cancer, arises from the intratumor synthesis of 5α-dihydrotestosterone through use of the precursor steroid dehydroepiandrosterone (DHEA) and is fueled by the steroidogenic enzymes 3β-hydroxysteroid dehydrogenase (3β-HSD1), aldoketoreductase (AKR1C3), and steroid 5-alpha reductase, type 1 (SRD5A1) present in cancer tissue. Sulfotransferase 2B1b (SULT2B1b) (in short, SULT2B) is a prostate-expressed hydroxysteroid SULT that converts cholesterol, oxysterols, and DHEA to 3β-sulfates. DHEA metabolism involving sulfonation by SULT2B can potentially interfere with intraprostate androgen synthesis due to reduction of free DHEA pool and, thus, conversion of DHEA to androstenedione. Here we report that in prostatectomy specimens from treatment-naive patients, SULT2B expression is markedly reduced in malignant tissue (P < .001, Mann-Whitney U test) compared with robust expression in adjacent nonmalignant glands. SULT2B was detected in formalin-fixed specimens by immunohistochemistry on individual sections and tissue array. Immunoblotting of protein lysates of frozen cancer and matched benign tissue confirmed immunohistochemistry results. An in-house–developed rabbit polyclonal antibody against full-length human SULT2B was validated for specificity and used in the analyses. Ligand-activated vitamin D receptor induced the SULT2B1 promoter in vivo in mouse prostate and increased SULT2B mRNA and protein levels in vitro in prostate cancer cells. A vitamin D receptor/retinoid X receptor-α–bound DNA element (with a DR7 motif) mediated induction of the transfected SULT2B1 promoter in calcitriol-treated cells. SULT2B knockdown caused an increased proliferation rate of prostate cancer cells upon stimulation by DHEA. These results suggest that the tumor tissue SULT2B level may partly control prostate cancer growth, and its induction in a therapeutic setting may inhibit disease

Prostate Cancer Screening Results from PLCO

Cancer.gov

Learn the results of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a large-scale clinical trial to determine whether certain cancer screening tests can help reduce deaths from prostate, lung, colorectal, and ovarian cancer.

Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 2, Insights into the Technical Rationale

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Fei, E-mail: feisun@ccmijesususon.com; Crisóstomo, Verónica, E-mail: crisosto@ccmijesususon.com; Báez-Díaz, Claudia, E-mail: cbaez@ccmijesususon.com

Rationale of prostatic artery embolization (PAE) in the treatment of symptomatic benign prostatic hyperplasia is conventionally believed to include two parts: shrinkage of the enlarged prostate gland as a result of PAE-induced ischemic infarction and potential effects to relax the increased prostatic smooth muscle tone by reducing the number and density of α{sub 1}-adrenergic receptor in the prostate stroma. This review describes new insights into the likely mechanisms behind PAE, such as ischemia-induced apoptosis, apoptosis enhanced by blockage of androgens circulation to the embolized prostate, secondary denervation following PAE, and potential effect of nitric oxide pathway immediately after embolization. Studiesmore » on therapeutic mechanisms in PAE may shed light on potentially new treatment strategies and development of novel techniques.« less

Maca (L. meyenii) for improving sexual function: a systematic review.

PubMed

Shin, Byung-Cheul; Lee, Myeong Soo; Yang, Eun Jin; Lim, Hyun-Suk; Ernst, Edzard

2010-08-06

Maca (Lepidium meyenii) is an Andean plant of the brassica (mustard) family. Preparations from maca root have been reported to improve sexual function. The aim of this review was to assess the clinical evidence for or against the effectiveness of the maca plant as a treatment for sexual dysfunction. We searched 17 databases from their inception to April 2010 and included all randomised clinical trials (RCTs) of any type of maca compared to a placebo for the treatment of healthy people or human patients with sexual dysfunction. The risk of bias for each study was assessed using Cochrane criteria, and statistical pooling of data was performed where possible. The selection of studies, data extraction, and validations were performed independently by two authors. Discrepancies were resolved through discussion by the two authors. Four RCTs met all the inclusion criteria. Two RCTs suggested a significant positive effect of maca on sexual dysfunction or sexual desire in healthy menopausal women or healthy adult men, respectively, while the other RCT failed to show any effects in healthy cyclists. The further RCT assessed the effects of maca in patients with erectile dysfunction using the International Index of Erectile Dysfunction-5 and showed significant effects. The results of our systematic review provide limited evidence for the effectiveness of maca in improving sexual function. However, the total number of trials, the total sample size, and the average methodological quality of the primary studies were too limited to draw firm conclusions. More rigorous studies are warranted.

Maca (L. meyenii) for improving sexual function: a systematic review

PubMed Central

2010-01-01

Background Maca (Lepidium meyenii) is an Andean plant of the brassica (mustard) family. Preparations from maca root have been reported to improve sexual function. The aim of this review was to assess the clinical evidence for or against the effectiveness of the maca plant as a treatment for sexual dysfunction. Methods We searched 17 databases from their inception to April 2010 and included all randomised clinical trials (RCTs) of any type of maca compared to a placebo for the treatment of healthy people or human patients with sexual dysfunction. The risk of bias for each study was assessed using Cochrane criteria, and statistical pooling of data was performed where possible. The selection of studies, data extraction, and validations were performed independently by two authors. Discrepancies were resolved through discussion by the two authors. Results Four RCTs met all the inclusion criteria. Two RCTs suggested a significant positive effect of maca on sexual dysfunction or sexual desire in healthy menopausal women or healthy adult men, respectively, while the other RCT failed to show any effects in healthy cyclists. The further RCT assessed the effects of maca in patients with erectile dysfunction using the International Index of Erectile Dysfunction-5 and showed significant effects. Conclusion The results of our systematic review provide limited evidence for the effectiveness of maca in improving sexual function. However, the total number of trials, the total sample size, and the average methodological quality of the primary studies were too limited to draw firm conclusions. More rigorous studies are warranted. PMID:20691074

Ratio of prostate specific antigen to the outer gland volume of prostrate as a predictor for prostate cancer.

PubMed

Zhang, Hai-Min; Yan, Yang; Wang, Fang; Gu, Wen-Yu; Hu, Guang-Hui; Zheng, Jun-Hua

2014-01-01

As a definite diagnosis of prostate cancer, puncture biopsy of the prostate is invasive method. The aim of this study was to evaluate the value of OPSAD (the ratio of PSA to the outer gland volume of prostate) as a non-invasive screening and diagnosis method for prostate cancer in a select population. The diagnosis data of 490 subjects undergoing ultrasound-guided biopsy of the prostate were retrospectively analyzed. This included 133 patients with prostate cancer, and 357 patients with benign prostate hyperplasia (BPH). The OPSAD was significantly greater in patients with prostate cancer (1.87 ± 1.26 ng/ml(2)) than those with BPH (0.44 ± 0.21 ng/ml(2)) (P < 0.05). Receiver operating characteristic (ROC) curve analysis revealed that the performance of OPSAD as a diagnostic tool is superior to PSA and PSAD for the diagnosis of prostate cancer. In the different groups divided according to the Gleason score of prostate cancer, OPSAD is elevated with the rise of the Gleason score. OPSAD may be used as a new indicator for the diagnosis and prognosis of prostate cancer, and it can reduce the use of unnecessary puncture biopsy of the prostate.

Maca (Lepidium meyenii) for treatment of menopausal symptoms: A systematic review.

PubMed

Lee, Myeong Soo; Shin, Byung-Cheul; Yang, Eun Jin; Lim, Hyun-Ja; Ernst, Edzard

2011-11-01

Maca (Lepidium meyenii), an Andean plant of the brassica (mustard) family has been used for centuries in the Andes as an adaptogenic plant to manage anemia, infertility and female hormone balance. The aim of this review was to assess the evidence for and against the effectiveness of the maca plant as a treatment for menopausal symptoms. We searched 17 databases from their inception up to June 2011 and included all randomized clinical trials (RCTs) that compared any type of maca-based intervention to a placebo for the treatment of menopausal symptoms. All studies were assessed for methodological quality using the Cochrane 'risk of bias' assessment tool. Four RCTs met all inclusion criteria. These RCTs tested the effects of maca on menopausal symptoms in healthy perimenopausal, early postmenopausal, and late postmenopausal women. Using the Kupperman Menopausal Index and the Greene Climacteric Score, all RCTs demonstrated favorable effects of maca. There have been very few rigorous trials of maca for menopausal symptoms. The results of our systematic review provide limited evidence for the effectiveness of maca as a treatment for menopausal symptoms. However, the total number of trials, the total sample size, and the average methodological quality of the primary studies, were too limited to draw firm conclusions. Furthermore, the safety has not been proved yet. Therefore, the efficacy and safety should be tested in larger studies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Inflammation in benign prostate tissue and prostate cancer in the finasteride arm of the Prostate Cancer Prevention Trial*

PubMed Central

Murtola, Teemu J.; Gurel, Bora; Umbehr, Martin; Lucia, M. Scott; Thompson, Ian M.; Goodman, Phyllis J.; Kristal, Alan R.; Parnes, Howard L.; Lippman, Scott M.; Sutcliffe, Siobhan; Peskoe, Sarah B.; Barber, John R.; Drake, Charles G.; Nelson, William G.; De Marzo, Angelo M.; Platz, Elizabeth A.

2015-01-01

Background A previous analysis of the placebo arm of the Prostate Cancer Prevention Trial (PCPT) reported 82% overall prevalence of intraprostatic inflammation and identified a link between inflammation and higher-grade prostate cancer and serum PSA. Here we studied these associations in the PCPT finasteride arm. Methods Prostate cancer cases (N=197) detected either on a clinically indicated biopsy or on protocol-directed end-of-study biopsy, and frequency-matched controls (N=248) with no cancer on an end-of-study biopsy were sampled from the finasteride arm. Inflammation in benign prostate tissue was visually assessed using digital images of H&E stained sections. Logistic regression was used for statistical analysis. Results In the finasteride arm, 91.6% of prostate cancer cases and 92.4% of controls had at least one biopsy core with inflammation in benign areas; p < 0.001 for difference compared to placebo arm. Overall, the odds of prostate cancer did not differ by prevalence (OR=0.90, 95% CI 0.44-1.84) or extent (P-trend=0.68) of inflammation. Inflammation was not associated with higher-grade disease (prevalence: OR=1.07, 95% CI 0.43-2.69). Furthermore, mean PSA concentration did not differ by the prevalence or extent of inflammationin either cases or controls. Conclusion The prevalence of intraprostatic inflammation was higher in the finasteride than placebo arm of the PCPT, with no association with higher-grade prostate cancer. Impact Finasteride may attenuate the association between inflammation and higher-grade prostate cancer. Moreover, the missing link between intraprostatic inflammation and PSA suggests that finasteride may reduce inflammation-associated PSA elevation. PMID:26715424

The use of maca (Lepidium meyenii) to improve semen quality: A systematic review.

PubMed

Lee, Myeong Soo; Lee, Hye Won; You, Sooseong; Ha, Ki-Tae

2016-10-01

The aim of this review was to assess the evidence for the effectiveness of maca (Lepidium meyenii) in improving semen quality. We searched 11 databases from their inception to March 2016 and included all clinical trials on the improvement of semen quality parameters in infertile and healthy men, regardless of the study design or the type of maca. The risk of bias for each study was assessed using the Cochrane criteria. The selection of studies, data extraction, and validation were performed independently by the first two authors. Discrepancies were resolved through discussion by the same two authors. Five studies - 3 randomized clinical trials (RCTs) and 2 uncontrolled observational studies (UOSs) - met all of the inclusion criteria. One RCT found favorable effects of maca on sperm mobility in infertile men. The two other RCTs showed positive effects of maca on several semen quality parameters in healthy men. The two UOSs also suggested favorable effects of maca on semen quality. The results of our systematic review provide suggestive evidence for the effectiveness of maca in improving semen quality. However, the total number of trials, the total sample size, and the risk of bias of the included studies prevent the drawing firm conclusions. More rigorous studies are warranted. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Acute and chronic dosing of Lepidium meyenii (Maca) on male rat sexual behavior.

PubMed

Lentz, Aaron; Gravitt, Karla; Carson, Culley C; Marson, Lesley

2007-03-01

The use of natural remedies for the treatment of sexual disorders is under current investigation. For generations people of the rural community in Peru have used Lepidium meyenii Walpers (Maca), because of their belief that it improves fertility and sexual desire. To determine the acute and chronic effects of Maca on male sexual behavior and to examine chronic administration of Maca on anxiety. Ejaculatory and mounting behavior and postejaculatory interval. Anxiety tests using an elevated plus maze, locomotion, and social interaction with another male. Maca (25 and 100 mg/kg) was orally administered to male rats for 30 days. Male sexual behavior was monitored after acute, 7 and 21 days of treatment. Anxiety behavior and locomotion were measured at 28-29 days using the elevated plus maze and social interaction tests. Maca treatment did not produce large changes in male sexual behavior. However, an increase in ejaculation latency and postejaculatory interval was observed after both acute and 7 days of treatment. After 21 days of treatment Maca had no effect on sexual behavior. Chronic administration of Maca did not increase locomotion or anxiety. Acute and short-term administration of Maca produced a small effect of rat male sexual behavior and long-term administration did not increase anxiety.

Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci.

PubMed

Amin Al Olama, Ali; Benlloch, Sara; Antoniou, Antonis C; Giles, Graham G; Severi, Gianluca; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Muir, Kenneth; Schleutker, Johanna; Henderson, Brian E; Haiman, Christopher A; Schumacher, Fredrick R; Pashayan, Nora; Pharoah, Paul D P; Ostrander, Elaine A; Stanford, Janet L; Batra, Jyotsna; Clements, Judith A; Chambers, Suzanne K; Weischer, Maren; Nordestgaard, Børge G; Ingles, Sue A; Sorensen, Karina D; Orntoft, Torben F; Park, Jong Y; Cybulski, Cezary; Maier, Christiane; Doerk, Thilo; Dickinson, Joanne L; Cannon-Albright, Lisa; Brenner, Hermann; Rebbeck, Timothy R; Zeigler-Johnson, Charnita; Habuchi, Tomonori; Thibodeau, Stephen N; Cooney, Kathleen A; Chappuis, Pierre O; Hutter, Pierre; Kaneva, Radka P; Foulkes, William D; Zeegers, Maurice P; Lu, Yong-Jie; Zhang, Hong-Wei; Stephenson, Robert; Cox, Angela; Southey, Melissa C; Spurdle, Amanda B; FitzGerald, Liesel; Leongamornlert, Daniel; Saunders, Edward; Tymrakiewicz, Malgorzata; Guy, Michelle; Dadaev, Tokhir; Little, Sarah J; Govindasami, Koveela; Sawyer, Emma; Wilkinson, Rosemary; Herkommer, Kathleen; Hopper, John L; Lophatonanon, Aritaya; Rinckleb, Antje E; Kote-Jarai, Zsofia; Eeles, Rosalind A; Easton, Douglas F

2015-07-01

Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history. The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs. ©2015 American Association for Cancer Research.

Low Prostate Concentration of Lycopene Is Associated with Development of Prostate Cancer in Patients with High-Grade Prostatic Intraepithelial Neoplasia

PubMed Central

Mariani, Simone; Lionetto, Luana; Cavallari, Michele; Tubaro, Andrea; Rasio, Debora; De Nunzio, Cosimo; Hong, Gena M.; Borro, Marina; Simmaco, Maurizio

2014-01-01

Prostate cancer (PC) is a frequent male malignancy and represents the second most diagnosed cancer in men. Since pre-cancerous lesions, i.e., the high-grade prostatic intraepithelial neoplasia (HGPIN), can be detected years before progression to PC, early diagnosis and chemoprevention are targeted strategies to reduce PC rates. Animal studies have shown that lycopene, a carotenoid contained in tomatoes, is a promising candidate for the chemoprevention of PC. However, its efficacy in humans remains controversial. The present study aimed to investigate the relevance of plasma and prostate concentration of lycopene after a lycopene-enriched diet in patients diagnosed with HGPIN. Thirty-two patients diagnosed with HGPIN were administered a lycopene-enriched diet (20–25 mg/day of lycopene; through 30 g/day of triple concentrated tomato paste) for 6 months. A 6-month follow-up prostate biopsy assessed progression to PC. Patients were classified into three groups according to the histopathological features of the 6-month follow-up biopsy results: prostatitis; HGPIN and PC. PSA and plasma lycopene levels were measured before and after the dietary lycopene supplementation. Prostatic lycopene concentration was only assessed after the supplementation diet. Only prostatic lycopene concentration showed significant differences between the three groups (p = 0.03). Prostatic lycopene concentration below a 1 ng/mg threshold was associated with PC at 6-month follow-up biopsy (p = 0.003). We observed no overall benefits from a 6-month lycopene supplementation, as the rate of HGPIN progression to PC in our population (9/32, 28%) was similar to rates reported in the literature. Baseline PSA levels also showed no significant changes after a lycopene-enriched diet. Our findings point to prostatic lycopene concentration as a promising biomarker of PC. Further prospective longitudinal studies are needed to assess the prognostic role of prostatic lycopene in PC. PMID:24451130

[Changes in prostatic circulation in response to laser therapy and magnetic therapy in patients with benign prostatic hyperplasia].

PubMed

2005-01-01

The results of preoperative preparation were analysed in 59 patients with prostatic benign hyperplasia (PBH) subjected to TUR. Treatment outcomes were assessed by transrectal ultrasound (color Doppler mapping) in two groups of patients. Group 1 received combined therapy including transrectal laser radiation of the prostate, group 2--transrectal magnetotherapy. The analysis showed that laser radiation reduced insignificantly the size of the prostate and adenomatous node, improved microcirculation and circulation in the prostate. This resulted in relief of inflammation and reduction of the number of postoperative inflammatory complications. Transrectal magnetotherapy has a positive effect on vascularization and hemodynamics of the prostate, local immunity, contamination of the tissues with pathogenic flora.

Comparison of Mineral Element Content in a Functional Food Maca (Lepidium meyenii Walp.) from Asia and South America.

PubMed

Zhang, Ji; Wang, Han-Mo; Zhao, Yan-Li; Zuo, Zhi-Tian; Wang, Yuan-Zhong; Jin, Hang

2015-01-01

Contents of eight mineral elements in maca (Lepidium meyenii Walp.) from China and Peru were determined by inductively coupled plasma optical emission spectroscopy. Cu contents in maca samples from China (2.5-31 mg kg(-1) dry weight, dw) were higher than the samples from Peru (<2.1 mg kg(-1) dw). Na in two samples from China was found to be significantly of high content (2400 and 2600 mg kg(-1) dw). The contents (mg kg(-1) dw) of B, Co, Cr, Li, Ni, and Zn were, respectively, 8.1-21, <0.023, <1.1~3.5, 0.020-0.17, 0.085-4.5, and 10-39 for the samples from China, while being 6.6-12, <0.023, <1.1~2.3, 0.035-0.063, 0.68-1.7, and 27-39 for the samples from Peru.

COX-2 and Prostate Cancer Angiogenesis

DTIC Science & Technology

2001-03-01

the optimal dosing and timing of a COX-2 inhibitor (NS398) in an animal model of human prostate cancer, (2)and (3) the mechanisms underlying the...cancer tissues (14) and that a COX-2 inhibitor selectively induces apoptosis in a prostate cancer cell line (15). We also demonstrated that treatment of...human prostate tumor-bearing mice with a selective COX-2 inhibitor (NS-398) significantly reduces tumor size, microvessel density and levels of a

Presence of PSA auto-antibodies in men with prostate abnormalities (prostate cancer/benign prostatic hyperplasia/prostatitis).

PubMed

Lokant, M T; Naz, R K

2015-04-01

Prostate-specific antigen (PSA), produced by the prostate, liquefies post-ejaculate semen. PSA is detected in semen and blood. Increased circulating PSA levels indicate prostate abnormality [prostate cancer (PC), benign prostatic hyperplasia (BPH), prostatitis (PTIS)], with variance among individuals. As the prostate has been proposed as an immune organ, we hypothesise that variation in PSA levels among men may be due to presence of auto-antibodies against PSA. Sera from healthy men (n = 28) and men having prostatitis (n = 25), BPH (n = 30) or PC (n = 29) were tested for PSA antibody presence using enzyme-linked immunosorbent assay (ELISA) values converted to standard deviation (SD) units, and Western blotting. Taking ≥2 SD units as cut-off for positive immunoreactivity, 0% of normal men, 0% with prostatitis, 33% with BPH and 3.45% with PC demonstrated PSA antibodies. One-way analysis of variance (anova) performed on the mean absorbance values and SD units of each group showed BPH as significantly different (P < 0.01) compared with PC and prostatitis. All others were nonsignificant (P < 0.05). Men (33%) with BPH had PSA antibodies by ELISA and Western blot. These discoveries may find clinical application in differential diagnosis among prostate abnormalities, especially differentiating BPH from prostate cancer and prostatitis. © 2014 Blackwell Verlag GmbH.

[Overexpression of miR-519d-3p inhibits the proliferation of DU-145 prostate cancer cells by reducing TRAF4].

PubMed

Li, Xiaohui; Han, Xingtao; Yang, Jinhui; Sun, Jiantao; Wei, Pengtao

2018-01-01

Objective To observe the effect of microRNA-519d-3p (miR-519d-3p) on the proliferation of prostate cancer cells and explore the possible molecular mechanism. Methods The expression level of miR-519d-3p in PC-3, DU-145, 22RV1, PC-3M, LNCaP human prostate cancer cells and RWPE-1 human normal prostate epithelial cells was detected by real-time quantitative PCR. miR-519d-3p mimics or negative control microRNAs (miR-NC) was transfected into the prostate cancer cells with the lowest level of miR-519d-3p expression. Transfection efficiency was examined. The effect of miR-519d-3p on the cell cycle of prostate cancer was detected by flow cytometry. MTT assay and plate clone formation assay were used to detect its effect on the proliferation of prostate cancer cells. Bioinformatics software was used to predict and dual luciferase reporter assay was used to validate the target gene of miR-519d-3p. Real-time quantitative PCR was used to detect the expression of miR-519d-3p target gene. Western blot analysis was used to detect the expression of target gene protein and downstream protein. Results The expression of miR-519d-3p in normal prostate epithelial cells was significantly higher than that in prostate cancer cells, and the lowest was found in DU-145 cells. After transfected with miR-519d-3p mimics, the expression level of miR-519d-3p in DU-145 cells increased significantly. Bioinformatics prediction and dual luciferase reporter gene confirmed that tumor necrosis factor receptor associated factor 4 (TRAF4) was the target gene of miR-519d-3p. Overexpression of miR-519d-3p significantly reduced the expression of TRAF4 gene and its downstream TGF-β signaling pathway proteins in the prostate cancer cells. Conclusion The expression of miR-519d-3p is down-regulated in prostate cancer cells. Overexpression of miR-519d-3p can inhibit the proliferation of prostate cancer cells. The possible mechanism is that miR-519d-3p inhibits the expression of TRAF4.

Prostate cancer and inflammation: the evidence

PubMed Central

Sfanos, Karen S; De Marzo, Angelo M

2014-01-01

Chronic inflammation is now known to contribute to several forms of human cancer, with an estimated 20% of adult cancers attributable to chronic inflammatory conditions caused by infectious agents, chronic noninfectious inflammatory diseases and / or other environmental factors. Indeed, chronic inflammation is now regarded as an ‘enabling characteristic’ of human cancer. The aim of this review is to summarize the current literature on the evidence for a role for chronic inflammation in prostate cancer aetiology, with a specific focus on recent advances regarding the following: (i) potential stimuli for prostatic inflammation; (ii) prostate cancer immunobiology; (iii) inflammatory pathways and cytokines in prostate cancer risk and development; (iv) proliferative inflammatory atrophy (PIA) as a risk factor lesion to prostate cancer development; and (v) the role of nutritional or other antiinflammatory compounds in reducing prostate cancer risk. PMID:22212087

Dietary Lycopene, Angiogenesis, and Prostate Cancer: A Prospective Study in the Prostate-Specific Antigen Era

PubMed Central

2014-01-01

Background The role of lycopene in prostate cancer prevention remains controversial. We examined the associations between dietary lycopene intake and prostate cancer, paying particular attention to the influence of prostate-specific antigen screening, and evaluated tissue biomarkers in prostate cancers in relation to lycopene intake. Methods Among 49898 male health professionals, we obtained dietary information through questionnaires and ascertained total and lethal prostate cancer cases from 1986 through January 31, 2010. Cox regression was used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). Tissue microarrays and immunohistochemistry were used to assess tumor biomarker expression in a subset of men. Two-sided χ2 tests were used to calculate the P values. Results Higher lycopene intake was inversely associated with total prostate cancer and more strongly with lethal prostate cancer (top vs bottom quintile: HR = 0.72; 95% CI = 0.56 to 0.94; P trend = .04). In a restricted population of screened participants, the inverse associations became markedly stronger (for lethal prostate cancer: HR = 0.47; 95% CI = 0.29 to 0.75; P trend = .009). Comparing different measures of dietary lycopene, early intake, but not recent intake, was inversely associated with prostate cancer. Higher lycopene intake was associated with biomarkers in the cancer indicative of less angiogenic potential. Conclusions Dietary intake of lycopene was associated with reduced risk of lethal prostate cancer and with a lesser degree of angiogenesis in the tumor. Because angiogenesis is a strong progression factor, an endpoint of lethal prostate cancer may be more relevant than an endpoint of indolent prostate cancer for lycopene in the era of highly prevalent prostate-specific antigen screening. PMID:24463248

Synergistic interaction of benign prostatic hyperplasia and prostatitis on prostate cancer risk

PubMed Central

Hung, S-C; Lai, S-W; Tsai, P-Y; Chen, P-C; Wu, H-C; Lin, W-H; Sung, F-C

2013-01-01

Background: The incidence of prostate cancer is much lower in Asian men than in Western men. This study investigated whether prostate cancer is associated with prostatitis, benign prostatic hyperplasia (BPH), and other medical conditions in the low-incidence population. Methods: From the claims data obtained from the universal National Health Insurance of Taiwan, we identified 1184 patients with prostate cancer diagnosed from 1997 to 2008. Controls comprised 4736 men randomly selected from a cancer-free population. Both groups were 50 years of age or above. Medical histories between the two groups were compared. Results: Multivariate logistic regression analysis showed that prostatitis and BPH had stronger association with prostate cancer than the other medical conditions tested. Compared with men without prostatitis and BPH, a higher odds ratio (OR) for prostate cancer was associated with BPH (26.2, 95% confidence interval (CI) 20.8–33.0) than with prostatitis (10.5, 95% CI=3.36–32.7). Men with both conditions had an OR of 49.2 (95% CI=34.7–69.9). Conclusion: Men with prostate cancer have strong association with prostatitis and/or BPH. Prostatitis interacts with BPH, resulting in higher estimated relative risk of prostate cancer in men suffering from both conditions. PMID:23612451

Macrophage Efferocytosis and Prostate Cancer Bone Metastasis

DTIC Science & Technology

2016-10-01

mediator of prostate cancer tumor growth. Specifically, phagocytic macrophages and efferocytosis were found to be upregulated in the blood of...patients with metastatic prostate cancer. Moreover, inhibiting phagocytic macrophages with the chemotherapeutic trabectedin reduced efferocytosis and

Prostate-specific antigen screening impacts on biochemical recurrence in patients with clinically localized prostate cancer.

PubMed

Hashimoto, Takeshi; Ohori, Makoto; Shimodaira, Kenji; Kaburaki, Naoto; Hirasawa, Yosuke; Satake, Naoya; Gondo, Tatsuo; Nakagami, Yoshihiro; Namiki, Kazunori; Ohno, Yoshio

2018-06-01

To clarify the impact of prostate-specific antigen screening on surgical outcomes of prostate cancer. Patients who underwent radical prostatectomy were divided into two groups according to prostate-specific antigen testing opportunity (group 1, prostate-specific antigen screening; group 2, non-prostate-specific antigen screening). Perioperative clinical characteristics were compared using the Wilcoxon rank-sum and χ 2 -tests. Cox proportional hazards models were used to identify independent predictors of postoperative biochemical recurrence-free survival. In total, 798 patients (63.2%) and 464 patients (36.8%) were categorized into groups 1 and 2, respectively. Group 2 patients were more likely to have a higher prostate-specific antigen level and age at diagnosis and larger prostate volume. Clinical T stage, percentage of positive cores and pathological Gleason score did not differ between the groups. The 5-year biochemical recurrence-free survival rate was 83.9% for group 1 and 71.0% for group 2 (P < 0.001). On multivariate analysis, prostate-specific antigen testing opportunity (hazard ratio 2.530; P < 0.001) was an independent predictive factor for biochemical recurrence after surgery, as well as pathological T stage, pathological Gleason score, positive surgical margin and lymphovascular invasion. Additional analyses showed that prostate-specific antigen screening had a greater impact on biochemical recurrence in a younger patients, patients with a high prostate-specific antigen level, large prostate volume and D'Amico high risk, and patients meeting the exclusion criteria of the Prostate Cancer Research International Active Surveillance study. Detection by screening results in favorable outcomes after surgery. Prostate-specific antigen screening might contribute to reducing biochemical recurrence in patients with localized prostate cancer. © 2018 The Japanese Urological Association.

A selective androgen receptor modulator that reduces prostate tumor size and prevents orchidectomy-induced bone loss in rats.

PubMed

Allan, George; Lai, Muh-Tsann; Sbriscia, Tifanie; Linton, Olivia; Haynes-Johnson, Donna; Bhattacharjee, Sheela; Dodds, Robert; Fiordeliso, James; Lanter, James; Sui, Zhihua; Lundeen, Scott

2007-01-01

The pharmacological activity of JNJ-26146900 is described. JNJ-26146900 is a nonsteroidal androgen receptor (AR) ligand with tissue-selective activity in rats. The compound was evaluated in in vitro and in vivo models of AR activity. It binds to the rat AR with a K(i) of 400nM and acts as a pure androgen antagonist in an in vitro cell-based assay. Its in vitro profile is similar to the androgen antagonist bicalutamide (Casodex). In intact rats, JNJ-26146900 reduces ventral prostate weight with an oral potency (ED(50)) of 20-30mg/kg, again comparable to that of bicalutamide. JNJ-26146900 prevented prostate tumor growth in the Dunning rat model, maximally inhibiting growth at a dose of 10mg/kg. It slowed tumor growth significantly in a CWR22-LD1 mouse xenograft model of human prostate cancer. It was tested in aged male rats for its ability to prevent bone loss and loss of lean body mass following orchidectomy. After 6 weeks of dosing, bone volume decreased by 33% in orchidectomized versus intact vehicle-treated rats with a probability (P) of less than 0.05, as measured by micro-computerized tomography analysis. At a dose of 30mg/kg, JNJ-26146900 significantly reduced castration-induced tibial bone loss as indicated by the following parameters: bone volume, trabecular connectivity, trabecular number and spacing between trabeculae. Bone mineral density decreased from 229+/-34mg/cm(3) of hydroxyapatite to 166+/-26mg/cm(3) following orchidectomy, and was maintained at 194+/-20mg/cm(3) with JNJ-26146900 treatment (P<0.05 relative to orchidectomy alone). Using magnetic resonance imaging, the compound was found to partially prevent orchidectomy-induced loss of lean body mass. Our data show that selective androgen receptor modulators (SARMs) have the potential for anabolic effects on bone and muscle while maintaining therapeutic efficacy in prostate cancer.

Diet and prostate cancer - a holistic approach to management.

PubMed

Cheetham, Philippa J; Katz, Aaron E

2011-10-01

There is now increasing evidence from epidemiologic surveys and from laboratory, intervention, and case-control studies that diet and lifestyle plays a crucial role in prostate cancer biology and tumorigenesis. This applies to both the development and progression of prostate cancer, although in many cases the specific initiating factors in the diet are poorly understood. Conversely, many nutrients and herbs also show significant promise in helping to treat prostate cancer by slowing progression and reducing recurrence, ultimately reducing the risk of morbidity and mortality from the disease. Furthermore for all grades of prostate cancer, nutritional interventions complement conventional treatment to improve response and quality of life. Slowing or even reversing the progression of, high-grade prostate intraepithelial neoplasia [HGPIN]). with chemo-preventative agents could be the best primary defense against prostate cancer, preventing it from occurring in the first place. The information given in this review about prostate cancer chemoprevention summarizes the key evidence for the role of different dietary components and their effect on prostate cancer prevention and progression. Most nutritional chemoprevention agents also have the added benefit of being beneficial for the cardiovascular system, bone health and for the prevention of other cancers.

Acute bacterial prostatitis and abscess formation.

PubMed

Lee, Dong Sup; Choe, Hyun-Sop; Kim, Hee Youn; Kim, Sun Wook; Bae, Sang Rak; Yoon, Byung Il; Lee, Seung-Ju

2016-07-07

The purpose of this study was to identify risk factors for abscess formation in acute bacterial prostatitis, and to compare treatment outcomes between abscess group and non-abscess group. This is a multicenter, retrospective cohort study. All patients suspected of having an acute prostatic infection underwent computed tomography or transrectal ultrasonography to discriminate acute prostatic abscesses from acute prostatitis without abscess formation. A total of 31 prostate abscesses were reviewed among 142 patients with acute prostatitis. Univariate analysis revealed that symptom duration, diabetes mellitus and voiding disturbance were predisposing factors for abscess formation in acute prostatitis. However, diabetes mellitus was not related to prostate abscess in multivariate analysis. Patients with abscesses <20 mm in size did not undergo surgery and were cured without any complications. In contrast, patients with abscesses >20 mm who underwent transurethral resection had a shorter duration of antibiotic treatment than did those who did not have surgery. Regardless of surgical treatment, both the length of hospital stay and antibiotic treatment were longer in patients with prostatic abscesses than they were in those without abscesses. However, the incidence of septic shock was not different between the two groups. A wide spectrum of microorganisms was responsible for prostate abscesses. In contrast, Escherichia coli was the predominant organism responsible for acute prostatitis without abscess. Imaging studies should be considered when patients with acute prostatitis have delayed treatment and signs of voiding disturbance. Early diagnosis is beneficial because prostatic abscesses require prolonged treatment protocols, or even require surgical drainage. Surgical drainage procedures such as transurethral resection of the prostate were not necessary in all patients with prostate abscesses. However, surgical intervention may have potential merits that reduce the

Polyphenols and Prostate Cancer Chemoprevention

DTIC Science & Technology

2004-03-01

The polyphenols, catechin, (-)- epigallocatechin -3- gallate ( EGCG ), genistein and resveratrol, are associated with reduced incidences of prostate and...protective effect without adverse effects with possible elevated exposure. The specific aims are 1) to investigate the potential of genistein, EGCG and...genistein, EGCG and resveratrol to regulate sex steroid- and specific growth factor-receptor and ligand expression as mechanism of prostate cancer

CX4945 suppresses the growth of castration-resistant prostate cancer cells by reducing AR-V7 expression.

PubMed

Deng, Chuangzhong; Chen, Jieping; Guo, Shengjie; Wang, Yanjun; Zhou, Qianghua; Li, Zaishang; Yang, Xingping; Yu, Xingsu; Zhang, Zhenfeng; Zhou, Fangjian; Han, Hui; Yao, Kai

2017-08-01

The aberrant expression of casein kinase 2 (CK2) has been reported to be involved in the tumorigenesis and progression of prostate cancer. The inhibition of CK2 activity represses androgen-dependent prostate cancer cells by attenuating the androgen receptor (AR) signaling pathway. In this study, we examined the effect of CK2 inhibition in castration-resistant prostate cancer (CRPC) cells, in which AR variants (ARVs) play a predominant role. A newly synthetic CK2 selective inhibitor CX4945 was utilized to study the effect of CK2 inhibition in CRPC cells by CCK8 assay and colony formation assay. Protein and mRNA levels of full-length AR (AR-FL) and AR-V7 were determined by qPCR and western blot, respectively. The nuclear translocation of p50 and p65 was assessed to reflect the activity of the NF-κB pathway. CX4945 reduced the proliferation of CRPC cells in a dose-dependent and time-dependent manner. AR-V7 rather than AR-FL was downregulated by CX4945 in both the mRNA and protein level. Furthermore, CX4945 could restore the sensitivity of CRPC cells to bicalutamide. The analysis of possible mechanisms demonstrated that the inhibition of CK2 diminished the phosphorylation of p65 at ser529 and thus attenuated the activity of the NF-κB pathway. The inhibition of CK2 by CX4945 can repress the viability of CRPC cells and restore their sensitivity to anti-androgen therapy by suppressing AR-V7. This finding presents a potential option for the treatment of prostate cancer, especially CRPC.

Comparison of Mineral Element Content in a Functional Food Maca (Lepidium meyenii Walp.) from Asia and South America

PubMed Central

Zhang, Ji; Wang, Han-Mo; Zhao, Yan-Li; Zuo, Zhi-Tian; Wang, Yuan-Zhong

2015-01-01

Contents of eight mineral elements in maca (Lepidium meyenii Walp.) from China and Peru were determined by inductively coupled plasma optical emission spectroscopy. Cu contents in maca samples from China (2.5–31 mg kg−1 dry weight, dw) were higher than the samples from Peru (<2.1 mg kg−1 dw). Na in two samples from China was found to be significantly of high content (2400 and 2600 mg kg−1 dw). The contents (mg kg−1 dw) of B, Co, Cr, Li, Ni, and Zn were, respectively, 8.1–21, <0.023, <1.1~3.5, 0.020–0.17, 0.085–4.5, and 10–39 for the samples from China, while being 6.6–12, <0.023, <1.1~2.3, 0.035–0.063, 0.68–1.7, and 27–39 for the samples from Peru. PMID:26236540

Prognostic value of saturated prostate cryoablation for localized prostate cancer.

PubMed

Chen, Chung-Hsin; Tai, Yi-Sheng; Pu, Yeong-Shiau

2015-10-01

To evaluate the oncological outcomes and complications of patients with saturated prostate cryoablation. A cohort of 208 patients cumulatively treated between June 2008 and December 2012 qualified for study inclusion, each undergoing total-gland cryoablation for prostate cancer. The degree of saturated prostate cryoablation was defined as the average prostate volume per cryoprobe (APVC), and divided into four groups (groups 1-4: <3 ml, 3 to <4 ml, 4 to <5 ml, ≧5 ml, respectively). Post-ablative complications were measured prospectively at weeks 1, 2, 4, 8, 12, and 24 by using the Common Terminology Criteria for Adverse Events. Biochemical failure was gauged by Phoenix criterion. The Kruskal-Wallis rank sum test and Chi-square test were used to compare clinical characteristics of therapeutic subsets. The Cox proportional hazard model was applied for comparison of recurrence risk between groups. APVC group 1 had the highest pre-operative PSA value and smallest prostate size among the groups. Multivariate analysis of risks of biochemical failures revealed that the larger the APVC, the higher the hazard (p for trend = 0.01). Compared to the group 1 patients, the hazard ratios of biochemical failures in groups 2-4 were 4.4 (confidence interval (CI): 0.5-37), 8.8 (CI 1.1-73), and 9.4 (CI 1.1-78), respectively. Nevertheless, the complication rate of APVC group 1 patients was similar to the other three groups. Saturated prostate cryoablation by reducing APVC would be beneficial for cancer control without compromising patient safety.

Isolation, purification, structural characterization and immunostimulatory activity of water-soluble polysaccharides from Lepidium meyenii.

PubMed

Zha, Zhengqi; Wang, Su-Yan; Chu, Weihua; Lv, Yang; Kan, Hongjin; Chen, Qiuli; Zhong, Lili; Yue, Long; Xiao, Jinna; Wang, Ying; Yin, Hongping

2018-03-01

A water-soluble polysaccharide LMP-1 was isolated and purified by ion-exchange chromatography from maca (Lepidium meyenii Walp.). LMP-1 has a molecular weight of 1.01 × 10 4  Da, and is composed of glucose and arabinose with a molar ratio of 7.03:1.08. Methylation and the 1D and 2D NMR spectroscopy of LMP-1 revealed that it is mainly composed of →4)-α-D-Glcp-(1→, →6)-α-D-Glcp-(1→, →3)-α-D-Glcp-(1→, and β-D-Araf-(1→, with branching at O-6 of →4,6)-α-D-Glcp-(1 → . LMP-1 showed up-regulation of Toll-like receptor 4 (TLR4) and Toll-like receptor 2 (TLR2). The upstream proteins of Toll-like receptors (TLRs) (CD14 and MD2) and mRNA level of IL-1β also increased. Increased transcription factor nuclear factor-kappa B (NF-κB) p65 was found in the nuclei and cytoplasm in LMP-1-treated RAW264.7 macrophages. These results indicated that LMP-1 activated RAW264.7 macrophages and elicited immunostimulatory activities via the TLRs/NF-κB signalling pathway. Copyright © 2018 Elsevier Ltd. All rights reserved.

Acute Bacterial Prostatitis: Diagnosis and Management.

PubMed

Coker, Timothy J; Dierfeldt, Daniel M

2016-01-15

Acute bacterial prostatitis is an acute infection of the prostate gland that causes pelvic pain and urinary tract symptoms, such as dysuria, urinary frequency, and urinary retention, and may lead to systemic symptoms, such as fevers, chills, nausea, emesis, and malaise. Although the true incidence is unknown, acute bacterial prostatitis is estimated to comprise approximately 10% of all cases of prostatitis. Most acute bacterial prostatitis infections are community acquired, but some occur after transurethral manipulation procedures, such as urethral catheterization and cystoscopy, or after transrectal prostate biopsy. The physical examination should include abdominal, genital, and digital rectal examination to assess for a tender, enlarged, or boggy prostate. Diagnosis is predominantly made based on history and physical examination, but may be aided by urinalysis. Urine cultures should be obtained in all patients who are suspected of having acute bacterial prostatitis to determine the responsible bacteria and its antibiotic sensitivity pattern. Additional laboratory studies can be obtained based on risk factors and severity of illness. Radiography is typically unnecessary. Most patients can be treated as outpatients with oral antibiotics and supportive measures. Hospitalization and broad-spectrum intravenous antibiotics should be considered in patients who are systemically ill, unable to voluntarily urinate, unable to tolerate oral intake, or have risk factors for antibiotic resistance. Typical antibiotic regimens include ceftriaxone and doxycycline, ciprofloxacin, and piperacillin/tazobactam. The risk of nosocomial bacterial prostatitis can be reduced by using antibiotics, such as ciprofloxacin, before transrectal prostate biopsy.

Flavonolignans and other constituents from Lepidium meyenii with activities in anti-inflammation and human cancer cell lines.

PubMed

Bai, Naisheng; He, Kan; Roller, Marc; Lai, Ching-Shu; Bai, Lu; Pan, Min-Hsiung

2015-03-11

From the roots of Lepidium meyenii Walpers (Brassicaceae) have been isolated and identified 2 flavonolignans, tricin 4'-O-[threo-β-guaiacyl-(7″-O-methyl)-glyceryl] ether (1) and tricin 4'-O-(erythro-β-guaiacyl-glyceryl) ether (2), along with 11 other known compounds, tricin (3), pinoresinol (4), 4-hydroxycinnamic acid (5), guanosine (6), glucotropaeolin (7), desulfoglucotropaeolin (8), 3-hydroxybenzylisothiocyanate (9), malic acid benzoate (10), 5-(hydroxymethyl)-2-furfural (11), d-phenylalanine (12), and vanillic acid 4-O-β-d-glucoside (13). Structures were elucidated on the basis of NMR and MS data. Some isolates and previously isolated lepidiline B (14) were tested for cytotoxicity in a small panel of human cancer cell lines (Hep G2, COLO 205, and HL-60) and for anti-inflammatory activities in LPS-treated RAW 264.7 macrophage. Among them, compounds 1 and 14 were modestly active for inhibiting nitrite production in macrophage. Compounds 1, 14, and 3 were demonstrated to be selectively active against HL-60 cells with IC50 values of 40.4, 52.0, and 52.1 μM, respectively.

Prostatitis

MedlinePlus

Prostatitis Overview Prostatitis is swelling and inflammation of the prostate gland, a walnut-sized gland situated directly below the bladder in ... produces fluid (semen) that nourishes and transports sperm. Prostatitis often causes painful or difficult urination. Other symptoms ...

Histopathology of prostate tissue after vascular-targeted photodynamic therapy for localized prostate cancer.

PubMed

Eymerit-Morin, Caroline; Zidane, Merzouka; Lebdai, Souhil; Triau, Stéphane; Azzouzi, Abdel Rahmene; Rousselet, Marie-Christine

2013-10-01

Low-risk prostate adenocarcinoma is classically managed either with active surveillance or radical therapy (such as external radiotherapy or radical prostatectomy), but both have significant side effects. Vascular-targeted photodynamic therapy (VTP) is a focal therapy proposed as an alternative approach for localized, low-volume, and low-Gleason score (≤6) carcinomas. We report histological modifications observed in prostate biopsies of 56 patients, performed 6 months after VTP using the photosensitizer TOOKAD® Soluble (WST11) and low-energy laser administered in the tumor area transperineally by optic fibers. In 53 patients, we observed sharply demarcated hyaline fibrotic scars, with or without rare atrophic glands, sometimes reduced to corpora amylacea surrounded by giant multinuclear macrophages. Mild chronic inflammation, hemosiderin, and coagulative necrosis were also observed. When residual cancer was present in a treated lobe (17 patients), it was always located outside the scar, most often close to the prostate capsule, and it showed no therapy-related modification. Histopathological interpretation of post-WST11 VTP prostate biopsies was straightforward, in contrast with that of prostate biopsies after radio or hormonal therapy, which introduces lesions difficult to interpret. VTP resulted in complete ablation of cancer in the targeted area.

Red Maca (Lepidium meyenii), a Plant from the Peruvian Highlands, Promotes Skin Wound Healing at Sea Level and at High Altitude in Adult Male Mice.

PubMed

Nuñez, Denisse; Olavegoya, Paola; Gonzales, Gustavo F; Gonzales-Castañeda, Cynthia

2017-12-01

Nuñez, Denisse, Paola Olavegoya, Gustavo F. Gonzales, and Cynthia Gonzales-Castañeda. Red maca (Lepidium meyenii), a plant from the Peruvian highlands, promotes skin wound healing at sea level and at high altitude in adult male mice. High Alt Med Biol 18:373-383, 2017.-Wound healing consists of three simultaneous phases: inflammation, proliferation, and remodeling. Previous studies suggest that there is a delay in the healing process in high altitude, mainly due to alterations in the inflammatory phase. Maca (Lepidium meyenii) is a Peruvian plant with diverse biological properties, such as the ability to protect the skin from inflammatory lesions caused by ultraviolet radiation, as well as its antioxidant and immunomodulatory properties. The aim of this study was to determine the effect of high altitude on tissue repair and the effect of the topical administration of the spray-dried extract of red maca (RM) in tissue repair. Studies were conducted in male Balb/c mice at sea level and high altitude. Lesions were inflicted through a 10 mm-diameter excisional wound in the skin dorsal surface. Treatments consisted of either (1) spray-dried RM extract or (2) vehicle (VH). Animals wounded at high altitude had a delayed healing rate and an increased wound width compared with those at sea level. Moreover, wounding at high altitude was associated with an increase in inflammatory cells. Treatment with RM accelerated wound closure, decreased the level of epidermal hyperplasia, and decreased the number of inflammatory cells at the wound site. In conclusion, RM at high altitude generate a positive effect on wound healing, decreasing the number of neutrophils and increasing the number of macrophages in the wound healing at day 7 postwounding. This phenomenon is not observed at sea level.

Nutraceuticals in Prostate Disease: The Urologist’s Role

PubMed Central

Curtis Nickel, J; Shoskes, Daniel; Roehrborn, Claus G; Moyad, Mark

2008-01-01

Interest in and use of complementary and alternative therapies, especially nutraceuticals, is high in prostate disease. These therapies have shown potential in benign prostatic hyperplasia (BPH), prostatitis, and prostate cancer. Some have produced results equal to or better than pharmaceuticals currently prescribed for BPH. In category III prostatitis, some nutraceuticals may offer relief to patients who get little from standard therapy. Because it is becoming apparent that inflammation may play a role in the progression of BPH and development of prostate cancer, nutraceuticals, which commonly have anti-inflammatory properties, may play a role. These therapies have also shown potential in prostate cancer treatment and prevention, especially those that also reduce cardiovascular events or risk. Nevertheless, uses of some nutraceuticals in prostate disease have had less desirable consequences, showing lack of efficacy, adulteration, and/or severe side effects or drug interactions. By ensuring that these therapies undergo careful study for effectiveness, quality, and safety, urologists can look forward to adding them to their evidence-based armamentarium for prostate disease. PMID:18836556

Hypoadiponectinemia, elevated iron and high-sensitivity C-reactive protein levels and their relation with prostate size in benign prostatic hyperplasia.

PubMed

Nandeesha, H; Eldhose, A; Dorairajan, L N; Anandhi, B

2017-09-01

Elevated iron, high-sensitivity C-reactive protein (CRP) and hypoadiponectinemia are known to initiate tumour development. There is paucity of data regarding the above-mentioned parameters and their relation with prostate size in benign prostatic hyperplasia (BPH). The present study was designed to assess the levels of iron, hs-CRP and adiponectin levels and their association with prostate size in BPH patients. A total of 37 BPH cases and 36 controls were enrolled in the study. Iron, hs-CRP and adiponectin were estimated in both the groups. Iron and hs-CRP were significantly increased and adiponectin was significantly reduced in BPH cases when compared with controls. Iron (r = .397, p = .015), hs-CRP (r = .341, p = .039) and adiponectin (r = -.464, p = .004) were significantly associated with prostate size in BPH cases. Multivariate linear regression analysis showed that iron acts as predictor of prostate size in BPH (R 2  = 0.395, β = 0.526, p = .001). We conclude that iron and hs-CRP are elevated and adiponectin is reduced in BPH cases and associated with prostate size. © 2016 Blackwell Verlag GmbH.

Antibody Responses to Prostate-Associated Antigens in Patients with Prostatitis and Prostate Cancer

PubMed Central

Maricque, Brett B.; Eickhoff, Jens C.; McNeel, Douglas G.

2010-01-01

Background An important focus of tumor immunotherapy has been the identification of appropriate antigenic targets. Serum-based screening approaches have led to the discovery of hundreds of tumor-associated antigens recognized by IgG. Our efforts to identify immunologically recognized proteins in prostate cancer have yielded a multitude of antigens, however prioritizing these antigens as targets for evaluation in immunotherapies has been challenging. In this report, we set out to determine whether the evaluation of multiple antigenic targets would allow the identification of a subset of antigens that are common immunologic targets in patients with prostate cancer. Methods Using a phage immunoblot approach, we evaluated IgG responses in patients with prostate cancer (n=126), patients with chronic prostatitis (n=45), and men without prostate disease (n=53). Results We found that patients with prostate cancer or prostatitis have IgG specific for multiple common antigens. A subset of 23 proteins was identified to which IgG were detected in 38% of patients with prostate cancer and 33% patients with prostatitis versus 6% of controls (p<0.001 and p=0.003, respectively). Responses to multiple members were not higher in patients with advanced disease, suggesting antibody immune responses occur early in the natural history of cancer progression. Conclusions These findings suggest an association between inflammatory conditions of the prostate and prostate cancer, and suggest that IgG responses to a panel of commonly recognized prostate antigens could be potentially used in the identification of patients at risk for prostate cancer or as a tool to identify immune responses elicited to prostate tissue. PMID:20632317

Reducing rectal injury in men receiving prostate cancer radiation therapy: current perspectives

PubMed Central

Serrano, Nicholas A; Kalman, Noah S; Anscher, Mitchell S

2017-01-01

Dose escalation is now the standard of care for the treatment of prostate cancer with radiation therapy. However, the rectum tends to be the dose-limiting structure when treating prostate cancer, given its close proximity. Early and late toxicities can occur when the rectum receives large doses of radiation therapy. New technologies allow for prevention of these toxicities. In this review, we examine the evidence that supports various dose constraints employed to prevent these rectal injuries from occurring. We also examine the use of intensity-modulated radiation therapy and how this compares to older radiation therapy techniques that allow for further sparing of the rectum during a radiation therapy course. We then review the literature on endorectal balloons and the effects of their daily use throughout a radiation therapy course. Tissue spacers are now being investigated in greater detail; these devices are injected into the rectoprostatic fascia to physically increase the distance between the prostate and the anterior rectal wall. Last, we review the use of systemic drugs, specifically statin medications and antihypertensives, as well as their impact on rectal toxicity. PMID:28814898

Molecular profiles of finasteride effects on prostate carcinogenesis.

PubMed

Li, Jin; Kim, Jeri

2009-06-01

Our inability to distinguish between low-grade prostate cancers that pose no threat and those that can kill compels newly diagnosed early prostate cancer patients to make decisions that may negatively affect their lives needlessly for years afterward. To reliably stratify patients into different risk categories and apply appropriate treatment, we need a better molecular understanding of prostate cancer progression. Androgen ablation therapy and 5-alpha reductase inhibitors reduce dihydrotestosterone levels and increase apoptosis. Because of the differing biological potentials of tumor cells, however, these treatments may, in some cases, worsen outcome by selecting for or inducing adaptation of stronger androgen receptor signaling pathways. Reduced dihydrotestosterone also may be associated with altered survival pathways. Complicating treatment effects further, molecular adaptation may be accelerated by interactions between epithelial and stromal cells. The hypothesis that early prostate cancer cells with differing biological potential may respond differently to finasteride treatment is worth testing. Ongoing studies using a systems biology approach in a preoperative prostate cancer setting are testing this hypothesis toward developing more-rational clinical interventions.

Vegetable and fruit intake after diagnosis and risk of prostate cancer progression.

PubMed

Richman, Erin L; Carroll, Peter R; Chan, June M

2012-07-01

Cruciferous vegetables, tomato sauce and legumes have been associated with reduced risk of incident advanced prostate cancer. In vitro and animal studies suggest these foods may inhibit progression of prostate cancer, but there are limited data in men. Therefore, we prospectively examined whether intake of total vegetables, and specifically cruciferous vegetables, tomato sauce and legumes, after diagnosis reduce risk of prostate cancer progression among 1,560 men diagnosed with non-metastatic prostate cancer and participating in the Cancer of the Prostate Strategic Urologic Research Endeavor, a United States prostate cancer registry. As a secondary analysis, we also examined other vegetable subgroups, total fruit and subgroups of fruits. The participants were diagnosed primarily at community-based clinics and followed from 2004 to 2009. We assessed vegetable and fruit intake via a semi-quantitative food frequency questionnaire, and ascertained prostate cancer outcomes via urologist report and medical records. We observed 134 events of progression (53 biochemical recurrences, 71 secondary treatments likely due to recurrence, 6 bone metastases and 4 prostate cancer deaths) during 3,171 person-years. Men in the fourth quartile of post-diagnostic cruciferous vegetable intake had a statistically significant 59% decreased risk of prostate cancer progression compared to men in the lowest quartile (hazard ratio (HR): 0.41; 95% confidence interval (CI): 0.22, 0.76; p-trend: 0.003). No other vegetable or fruit group was statistically significantly associated with risk of prostate cancer progression. In conclusion, cruciferous vegetable intake after diagnosis may reduce risk of prostate cancer progression. Copyright © 2011 UICC.

Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery

PubMed Central

Demark-Wahnefried, Wendy; Polascik, Thomas J.; George, Stephen L.; Switzer, Boyd R.; Madden, John F.; Ruffin, Mack T.; Snyder, Denise C.; Owzar, Kouros; Hars, Vera; Albala, David M.; Walther, Philip J.; Robertson, Cary N.; Moul, Judd W.; Dunn, Barbara K.; Brenner, Dean; Minasian, Lori; Stella, Philip; Vollmer, Robin T.

2009-01-01

Background Prostate cancer affects one-out-of-six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods We undertook a multi-site, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n=161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: 1) control (usual diet); 2) flaxseed-supplemented diet (30 g/day); 2) low-fat diet (<20% total energy); or 4) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and prior to surgery and analyzed for prostate specific antigen (PSA), sex hormone binding globulin, testosterone, insulin-like growth factor-1 and binding protein-3, c-reactive protein, and total and low density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. Results Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67 positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) vs. 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serological endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P=0.048). Conclusions Findings suggest that flaxseed is safe, and associated with biologic alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol. PMID:19064574

Smooth muscle cell-specific knockout of androgen receptor: a new model for prostatic disease.

PubMed

Welsh, Michelle; Moffat, Lindsey; McNeilly, Alan; Brownstein, David; Saunders, Philippa T K; Sharpe, Richard M; Smith, Lee B

2011-09-01

Androgen-driven stromal-epithelial interactions play a key role in normal prostate development and function as well as in the progression of common prostatic diseases such as benign prostatic hyperplasia and prostate cancer. However, exactly how, and via which cell type, androgens mediate their effects in the adult prostate remains unclear. This study investigated the role for smooth muscle (SM) androgen signaling in normal adult prostate homeostasis and function using mice in which androgen receptor was selectively ablated from prostatic SM cells. In adulthood the knockout (KO) mice displayed a 44% reduction in prostate weight and exhibited histological abnormalities such as hyperplasia, inflammation, fibrosis, and reduced expression of epithelial, SM, and stem cell identify markers (e.g. p63 reduced by 27% and Pten by 31%). These changes emerged beyond puberty and were not explained by changes in serum hormones. Furthermore, in response to exogenous estradiol, adult KO mice displayed an 8.5-fold greater increase in prostate weight than controls and developed urinary retention. KO mice also demonstrated a reduced response to castration compared with controls. Together these results demonstrate that prostate SM cells are vital in mediating androgen-driven stromal-epithelial interactions in adult mouse prostates, determining cell identity and function and limiting hormone-dependent epithelial cell proliferation. This novel mouse model provides new insight into the possible role for SM androgen action in prostate disease.

Identification and characterization of microRNAs and their targets in high-altitude stress-adaptive plant maca (Lepidium meyenii Walp).

PubMed

Paul, Sujay

2017-06-01

MicroRNAs (miRNAs) are endogenous, short (~21-nucleotide), non-coding RNA molecules that play pivotal roles in plant growth, development, and stress response signaling. In this study using recently published draft genome sequence of a high-altitude plant maca (Lepidium meyenii Walp) and applying genome-wide computational-based approaches, a total of 62 potentially conserved miRNAs belonging to 28 families were identified and four (lme-miR160a, lme-miR164c, lme-miR 166a, and lme-miR 319a) of them further validated by RT-PCR. Deploying psRNATarget tool a total of 99 potential miRNA target transcripts were also identified in maca. Targets include a number of transcription factors like Squamosa promoter-binding, NAC, MYB, auxin response factor, APETALA, WRKY, and F-box protein. To the best of my knowledge, this is the first genome-based miRNA profiling of a high-altitude plant.

Postoperative haemorrhage following transurethral resection of the prostate (TURP) and photoselective vaporisation of the prostate (PVP)

PubMed Central

Lynch, Mark; Sriprasad, Seshadri; Subramonian, Kesavapillai; Thompson, Peter

2010-01-01

INTRODUCTION Intractable haemorrhage after endoscopic surgery, including transurethral resection of the prostate (TURP) and photoselective vaporisation of the prostate (PVP), is uncommon but a significant and life-threatening problem. The knowledge and technical experience to deal with this complication may not be wide-spread among urologists and trainees. We describe our series of TURPs and PVPs and the incidence of postoperative bleeding requiring intervention. PATIENTS AND METHODS We retrospectively reviewed 437 TURPs and 590 PVPs over 3 years in our institution. We describe the conservative, endoscopic and open prostatic packing techniques used for patients who experienced postoperative bleeding. RESULTS Of 437 TURPs, 19 required endoscopic intervention for postoperative bleeding. Of 590 PVPs, two patients were successfully managed endoscopically for delayed haemorrhage at 7 and 13 days post-surgery, respectively. In one TURP and one PVP patient, endoscopic management was insufficient to control postoperative haemorrhage and open exploration and packing of the prostatic cavity was performed. CONCLUSIONS Significant bleeding after endoscopic prostatic surgery is still a potentially life-threatening complication. Prophylactic measures have been employed to reduce peri-operative bleeding but persistent bleeding post-endoscopic prostatic surgery should be treated promptly to prevent the risk of rapid deterioration. We demonstrated that the technique of open prostate packing may be life-saving. PMID:20522311

Ejaculatory function after permanent 125I prostate brachytherapy for localized prostate cancer.

PubMed

Huyghe, Eric; Delannes, Martine; Wagner, Fabien; Delaunay, Boris; Nohra, Joe; Thoulouzan, Matthieu; Shut-Yee, J Yeung; Plante, Pierre; Soulie, Michel; Thonneau, Patrick; Bachaud, Jean Marc

2009-05-01

Ejaculatory function is an underreported aspect of male sexuality in men treated for prostate cancer. We conducted the first detailed analysis of ejaculatory function in patients treated with permanent (125)I prostate brachytherapy for localized prostate cancer. Of 270 sexually active men with localized prostate cancer treated with permanent (125)I prostate brachytherapy, 241 (89%), with a mean age of 65 years (range, 43-80), responded to a mailed questionnaire derived from the Male Sexual Health Questionnaire regarding ejaculatory function. Five aspects of ejaculatory function were examined: frequency, volume, dry ejaculation, pleasure, and pain. Of the 241 sexually active men, 81.3% had conserved ejaculatory function after prostate brachytherapy; however, the number of patients with rare/absent ejaculatory function was double the pretreatment number (p < .0001). The latter finding was correlated with age (p < .001) and the preimplant International Index of Erectile Function score (p < .001). However, 84.9% of patients with maintained ejaculatory function after implantation reported a reduced volume of ejaculate compared with 26.9% before (p < .001), with dry ejaculation accounting for 18.7% of these cases. After treatment, 30.3% of the patients experienced painful ejaculation compared with 12.9% before (p = .0001), and this was associated with a greater number of implanted needles (p = .021) and the existence of painful ejaculation before implantation (p < .0001). After implantation, 10% of patients who continued to be sexually active experienced no orgasm compared with only 1% before treatment. in addition, more patients experienced late/difficult or weak orgasms (p = .001). Most men treated with brachytherapy have conserved ejaculatory function after prostate brachytherapy. However, most of these men experience a reduction in volume and a deterioration in orgasm.

The microbiome in prostate inflammation and prostate cancer.

PubMed

Porter, Corey M; Shrestha, Eva; Peiffer, Lauren B; Sfanos, Karen S

2018-05-23

The human microbiome may influence prostate cancer initiation and/or progression through both direct and indirect interactions. To date, the majority of studies have focused on direct interactions including the influence of prostate infections on prostate cancer risk and, more recently, on the composition of the urinary microbiome in relation to prostate cancer. Less well understood are indirect interactions of the microbiome with prostate cancer, such as the influence of the gastrointestinal or oral microbiota on pro- or anti-carcinogenic xenobiotic metabolism, and treatment response. We review the literature to date on direct and indirect interactions of the microbiome with prostate inflammation and prostate cancer. Emerging studies indicate that the microbiome can influence prostate inflammation in relation to benign prostate conditions such as prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia, as well as in prostate cancer. We provide evidence that the human microbiome present at multiple anatomic sites (urinary tract, gastrointestinal tract, oral cavity, etc.) may play an important role in prostate health and disease. In health, the microbiome encourages homeostasis and helps educate the immune system. In dysbiosis, a systemic inflammatory state may be induced, predisposing remote anatomical sites to disease, including cancer. The microbiome's ability to affect systemic hormone levels may also be important, particularly in a disease such as prostate cancer that is dually affected by estrogen and androgen levels. Due to the complexity of the potential interconnectedness between prostate cancer and the microbiome, it is vital to further explore and understand the relationships that are involved.

Aqueous and hydroalcoholic extracts of Black Maca (Lepidium meyenii) improve scopolamine-induced memory impairment in mice.

PubMed

Rubio, Julio; Dang, Haixia; Gong, Mengjuan; Liu, Xinmin; Chen, Shi-Lin; Gonzales, Gustavo F

2007-10-01

Lepidium meyenii Walp. (Brassicaceae), known as Maca, is a Peruvian hypocotyl growing exclusively between 4,000 and 4,500 m altitude in the central Peruvian Andes, particularly in Junin plateau. Previously, Black variety of Maca showed to be more beneficial than other varieties of Maca on learning and memory in ovariectomized mice on the water finding test. The present study aimed to test two different doses of aqueous (0.50 and 2.00 g/kg) and hydroalcoholic (0.25 and 1.00 g/kg) extracts of Black Maca administered for 35 days on memory impairment induced by scopolamine (1mg/kg body weight i.p.) in male mice. Memory and learning were evaluated using the water Morris maze and the step-down avoidance test. Brain acetylcholinesterase (AChE) and monoamine oxidase (MAO) activities in brain were also determined. Both extracts of Black Maca significantly ameliorated the scopolamine-induced memory impairment as measured in both the water Morris maze and the step-down avoidance tests. Black Maca extracts inhibited AChE activity, whereas MAO activity was not affected. These results indicate that Black Maca improves scopolamine-induced memory deficits.

Nociceptive and Inflammatory Mediator Upregulation in a Mouse Model of Chronic Prostatitis

PubMed Central

Schwartz, Erica S.; Xie, Amy; La, Jun-Ho; Gebhart, G.F.

2015-01-01

Chronic nonbacterial prostatitis, characterized by genitourinary pain in the pelvic region in the absence of an identifiable cause, is common in adult males. Surprisingly, the sensory innervation of the prostate and mediators that sensitize its innervation have received little attention. We thus characterized a mouse model of chronic prostatitis, focusing on the prostate innervation and how organ inflammation affects gene expression of putative nociceptive markers in prostate afferent somata in dorsal root ganglia (DRG) and mediators in the prostate. Retrograde tracing (fast blue, FB) from the prostate revealed that thoracolumbar (TL) and lumbosacral (LS) DRG are the principal sources of somata of prostate afferents. Nociceptive markers (e.g., TRP, TREK and P2X channels) were upregulated in FB-labeled TL and LS somata for up to four weeks after inflaming the prostate (intra-prostate injection of zymosan). Prostatic inflammation was evident histologically, by monocyte infiltration and a significant increase in mast cell tryptase activity 14, 21 and 28 days after zymosan injection. Interleukin-10 and NGF were also significantly upregulated in the prostate throughout the four weeks of inflammation. Open field pain-related behaviors (e.g., rearing) were unchanged in prostate-inflamed mice, suggesting the absence of ongoing nociception, but withdrawal thresholds to lower abdominal pressure were significantly reduced. The increases in IL-10, mast cell tryptase and NGF in the inflamed prostate were cotemporaneous with reduced thresholds to probing of the abdomen and upregulation of nociceptive markers in DRG somata innervating the prostate. The results provide insight and direction for study of mechanisms underlying pain in chronic prostatitis. PMID:25915147

Prostate-specific membrane antigen-targeted liposomes specifically deliver the Zn(2+) chelator TPEN inducing oxidative stress in prostate cancer cells.

PubMed

Stuart, Christopher H; Singh, Ravi; Smith, Thomas L; D'Agostino, Ralph; Caudell, David; Balaji, K C; Gmeiner, William H

2016-05-01

To evaluate the potential use of zinc chelation for prostate cancer therapy using a new liposomal formulation of the zinc chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN). TPEN was encapsulated in nontargeted liposomes or liposomes displaying an aptamer to target prostate cancer cells overexpression prostate-specific membrane antigen. The prostate cancer selectivity and therapeutic efficacy of liposomal (targeted and nontargeted) and free TPEN were evaluated in vitro and in tumor-bearing mice. TPEN chelates zinc and results in reactive oxygen species imbalance leading to cell death. Delivery of TPEN using aptamer-targeted liposomes results in specific delivery to targeted cells. In vivo experiments show that TPEN-loaded, aptamer-targeted liposomes reduce tumor growth in a human prostate cancer xenograft model.

A novel curvilinear approach for prostate seed implantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Podder, Tarun K.; Dicker, Adam P.; Hutapea, Parsaoran

Purpose: A new technique called ''curvilinear approach'' for prostate seed implantation has been proposed. The purpose of this study is to evaluate the dosimetric benefit of curvilinear distribution of seeds for low-dose-rate (LDR) prostate brachytherapy. Methods: Twenty LDR prostate brachytherapy cases planned intraoperatively with VariSeed planning system and I-125 seeds were randomly selected as reference rectilinear cases. All the cases were replanned by using curved-needle approach keeping the same individual source strength and the volume receiving 100% of prescribed dose 145 Gy (V{sub 100}). Parameters such as number of needles, seeds, and the dose coverage of the prostate (D{sub 90},more » V{sub 150}, V{sub 200}), urethra (D{sub 30}, D{sub 10}) and rectum (D{sub 5}, V{sub 100}) were compared for the rectilinear and the curvilinear methods. Statistical significance was assessed using two-tailed student's t-test. Results: Reduction of the required number of needles and seeds in curvilinear method were 30.5% (p < 0.001) and 11.8% (p < 0.49), respectively. Dose to the urethra was reduced significantly; D{sub 30} reduced by 10.1% (p < 0.01) and D{sub 10} reduced by 9.9% (p < 0.02). Reduction in rectum dose D{sub 5} was 18.5% (p < 0.03) and V{sub 100} was also reduced from 0.93 cc in rectilinear to 0.21 cc in curvilinear (p < 0.001). Also the V{sub 150} and V{sub 200} coverage of prostate reduced by 18.8% (p < 0.01) and 33.9% (p < 0.001), respectively. Conclusions: Significant improvement in the relevant dosimetric parameters was observed in curvilinear needle approach. Prostate dose homogeneity (V{sub 150}, V{sub 200}) improved while urethral dose was reduced, which might potentially result in better treatment outcome. Reduction in rectal dose could potentially reduce rectal toxicity and complications. Reduction in number of needles would minimize edema and thereby could improve postimplant urinary incontinence. This study indicates that the curvilinear

Saw palmetto for prostate disorders.

PubMed

Gordon, Andrea E; Shaughnessy, Allen F

2003-03-15

Saw palmetto is an herbal product used in the treatment of symptoms related to benign prostatic hyperplasia. The active component is found in the fruit of the American dwarf palm tree. Studies have demonstrated the effectiveness of saw palmetto in reducing symptoms associated with benign prostatic hyperplasia. Saw palmetto appears to have efficacy similar to that of medications like finasteride, but it is better tolerated and less expensive. There are no known drug interactions with saw palmetto, and reported side effects are minor and rare. No data on its long-term usage are available. The herbal product also has been used to treat chronic prostatitis, but currently there is no evidence of its efficacy.

A Neighborhood-Based Intervention to Reduce Prostate Cancer Disparities

DTIC Science & Technology

2017-10-01

for men from the neighborhoods. We also began recruitment and sessions to test the PCa educational intervention. Results: Focus group participants had...making about PCa screening Sub-aim 4: To observe the rates of PCa screening in the intervention and control groups 2. Keywords Prostate Cancer...mobilization of community health workers from high risk neighborhoods. Recruitment and conduct of “ control ” group educational sessions. Establishment of

Bacterial prostatitis.

PubMed

Gill, Bradley C; Shoskes, Daniel A

2016-02-01

The review provides the infectious disease community with a urologic perspective on bacterial prostatitis. Specifically, the article briefly reviews the categorization of prostatitis by type and provides a distillation of new findings published on bacterial prostatitis over the past year. It also highlights key points from the established literature. Cross-sectional prostate imaging is becoming more common and may lead to more incidental diagnoses of acute bacterial prostatitis. As drug resistance remains problematic in this condition, the reemergence of older antibiotics such as fosfomycin, has proven beneficial. With regard to chronic bacterial prostatitis, no clear clinical risk factors emerged in a large epidemiological study. However, bacterial biofilm formation has been associated with more severe cases. Surgery has a limited role in bacterial prostatitis and should be reserved for draining of a prostatic abscess or the removal of infected prostatic stones. Prostatitis remains a common and bothersome clinical condition. Antibiotic therapy remains the basis of treatment for both acute and chronic bacterial prostatitis. Further research into improving prostatitis treatment is indicated.

Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate-cancer associated SNPs for familial disease

PubMed Central

Teerlink, Craig C.; Thibodeau, Stephen N.; McDonnell, Shannon K.; Schaid, Daniel J.; Rinckleb, Antje; Maier, Christiane; Vogel, Walther; Cancel-Tassin, Geraldine; Egrot, Christophe; Cussenot, Olivier; Foulkes, William D.; Giles, Graham G.; Hopper, John L.; Severi, Gianluca; Eeles, Ros; Easton, Douglas; Kote-Jarai, Zsofia; Guy, Michelle; Cooney, Kathleen A.; Ray, Anna M.; Zuhlke, Kimberly A.; Lange, Ethan M.; FitzGerald, Liesel M.; Stanford, Janet L.; Ostrander, Elaine A.; Wiley, Kathleen E.; Isaacs, Sarah D.; Walsh, Patrick C.; Isaacs, William B.; Wahlfors, Tiina; Tammela, Teuvo; Schleutker, Johanna; Wiklund, Fredrik; Grönberg, Henrik; Emanuelsson, Monica; Carpten, John; Bailey-Wilson, Joan; Whittemore, Alice S.; Oakley-Girvan, Ingrid; Hsieh, Chih-Lin; Catalona, William J.; Zheng, S. Lilly; Jin, Guangfu; Lu, Lingyi; Xu, Jianfeng; Camp, Nicola J.; Cannon-Albright, Lisa A.

2013-01-01

Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p≤1E−3) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may be contribute risk to aggressive disease. PMID:24162621

Benign prostatic hyperplasia (BPH) management in the primary care setting.

PubMed

Kapoor, Anil

2012-10-01

Benign prostate hyperplasia (BPH) occurs in up to 50% of men by age 50, and the incidence increases with age. This common clinical problem is diagnosed by history, including the International Prostate Symptom Score (IPSS) questionnaire, and physical examination by digital rectal examination (DRE). Initial management for BPH includes lifestyle modification, and smooth muscle relaxant alpha blocker therapy. Alpha blockers usually take effect quickly within 3-5 days, and have minimal side effects. Current commonly used alpha blockers include the selective alpha blockers tamsulosin (Flomax), alfusosin (Xatral), and silodosin (Rapaflo). For patients with larger prostates, the 5-alpha reductase inhibitor class (finasteride (Proscar) and dutasteride (Avodart)) work effectively to shrink prostate stroma resulting in improved voiding. The 5-ARI class of drugs, in addition to reducing prostate size, also reduce the need for future BPH-related surgery, and reduce the risk of future urinary retention. Drugs from the phosphodiesterase-5 (PDE-5) inhibitor class may now be considered for treating BPH. Once daily 5 mg tadalafil has been shown to improve BPH-related symptoms and is currently approved to treat patients with BPH. Referral to a urologist can be considered for patients with a rising prostate-specific antigen (PSA), especially while on 5-ARI, failure of urinary symptom control despite maximal medical therapy, suspicion of prostate cancer, hematuria, recurrent urinary infections, urinary retention, or renal failure. Currently the primary care physician is armed with multiple treatment options to effectively treat men with symptomatic BPH.

Nociceptive and inflammatory mediator upregulation in a mouse model of chronic prostatitis.

PubMed

Schwartz, Erica S; Xie, Amy; La, Jun-Ho; Gebhart, G F

2015-08-01

Chronic nonbacterial prostatitis, characterized by genitourinary pain in the pelvic region in the absence of an identifiable cause, is common in adult males. Surprisingly, the sensory innervation of the prostate and mediators that sensitize its innervation have received little attention. We thus characterized a mouse model of chronic prostatitis, focusing on the prostate innervation and how organ inflammation affects gene expression of putative nociceptive markers in prostate afferent somata in dorsal root ganglia (DRG) and mediators in the prostate. Retrograde tracing (fast blue) from the prostate revealed that thoracolumbar and lumbosacral DRG are the principal sources of somata of prostate afferents. Nociceptive markers (eg, transient receptor potential, TREK, and P2X channels) were upregulated in fast blue-labeled thoracolumbar and lumbosacral somata for up to four weeks after inflaming the prostate (intraprostate injection of zymosan). Prostatic inflammation was evident histologically, by monocyte infiltration and a significant increase in mast cell tryptase activity 14, 21, and 28 days after zymosan injection. Interleukin 10 and NGF were also significantly upregulated in the prostate throughout the 4 weeks of inflammation. Open-field pain-related behaviors (eg, rearing) were unchanged in prostate-inflamed mice, suggesting the absence of ongoing nociception, but withdrawal thresholds to lower abdominal pressure were significantly reduced. The increases in IL-10, mast cell tryptase, and NGF in the inflamed prostate were cotemporaneous with reduced thresholds to probing of the abdomen and upregulation of nociceptive markers in DRG somata innervating the prostate. The results provide insight and direction for the study of mechanisms underlying pain in chronic prostatitis.

A Cinematic Magnetic Resonance Imaging Study of Milk of Magnesia Laxative and an Antiflatulent Diet to Reduce Intrafraction Prostate Motion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nichol, Alan M.; Warde, Padraig R.; Lockwood, Gina A.

Purpose: To determine the reduction of prostate motion during a typical radiotherapy (RT) fraction from a bowel regimen comprising an antiflatulent diet and daily milk of magnesia. Methods and Materials: Forty-two patients with T1c-T2c prostate cancer voided the bladder and rectum before three cinematic magnetic resonance imaging scans obtained every 9 s for 9 min in a vacuum immobilization device. The MRIs were at baseline without bowel regimen (MRI-BL), before CT planning with bowel regimen (MRI-CT), and before a randomly assigned RT fraction (1-42) with bowel regimen (MRI-RT). A single observer tracked displacement of the posterior midpoint (PM) of themore » prostate. The primary endpoints were comparisons of the proportion of time that the PM was displaced >3 mm (PTPM3) from its initial position, and the secondary endpoints were comparisons of the reduction of initial rectal area, with and without the bowel regimen. Results: The mean rectal area was: 13.5 cm{sup 2} at MRI-BL, 12.7 cm{sup 2} at MRI-CT, and 12.3 cm{sup 2} at MRI-RT (MRI-BL vs. MRI-CT, p = 0.11; MRI-BL vs. MRI-CT, p = 0.07). Moving rectal gas alone (56%) and moving gas and stool (18%) caused 74% of intrafraction prostate motion. The PTPM3 was 11.3% at MRI-BL, 4.8% at MRI-CT, and 12.0% at MRI-RT (MRI-BL vs. MRI-CT, p = 0.12; MRI-BL vs. MRI-RT, p = 0.89). Conclusion: For subjects voiding their rectum before imaging, an antiflatulent diet and milk of magnesia laxative did not significantly reduce initial rectal area or intrafraction prostate motion.« less

Urinary tract infections and bacterial prostatitis in men.

PubMed

Wagenlehner, Florian M E; Weidner, Wolfgang; Pilatz, Adrian; Naber, Kurt G

2014-02-01

The purpose of this review is to highlight advances in research on urinary tract infections (UTIs) and bacterial prostatitis in men in the preceding year. The antiseptic properties of the prostate secretions might be an important factor for prevention of recurrency. Risk factors for UTI in men include prostate enlargement and urological interventions, such as transrectal prostate biopsy. Preventive treatment of prostate enlargement has been demonstrated to reduce frequency of UTI. Ensuing infections after prostate biopsy, such as UTI and bacterial prostatitis, are increasing due to increasing rates of fluoroquinolone resistance. The increasing global antibiotic resistance also significantly affects management of UTI in men, and therefore calls for alternative strategies.Apart from prevention of complicating factors leading to UTI, a more thorough understanding of the pathophysiology may play a more important role in the future, to define new targets for treatment. Interesting results that might interfere with the intracellular mucosal bacterial load in the bladder wall have been found in the last years. UTI in men and bacterial prostatitis are currently underrepresented in the medical literature. Increasing antibacterial resistance calls for novel strategies in the prevention and management of UTI and bacterial prostatitis in men.

The Prostate

MedlinePlus

... Publications Reports What You Need To Know About™ Prostate Cancer This booklet is about prostate cancer. Learning about medical care for your cancer ... ePub This booklet covers: The anatomy of the prostate and basics about prostate cancer Treatments for prostate ...

Vitamins, metabolomics, and prostate cancer.

PubMed

Mondul, Alison M; Weinstein, Stephanie J; Albanes, Demetrius

2017-06-01

How micronutrients might influence risk of developing adenocarcinoma of the prostate has been the focus of a large body of research (especially regarding vitamins E, A, and D). Metabolomic profiling has the potential to discover molecular species relevant to prostate cancer etiology, early detection, and prevention, and may help elucidate the biologic mechanisms through which vitamins influence prostate cancer risk. Prostate cancer risk data related to vitamins E, A, and D and metabolomic profiling from clinical, cohort, and nested case-control studies, along with randomized controlled trials, are examined and summarized, along with recent metabolomic data of the vitamin phenotypes. Higher vitamin E serologic status is associated with lower prostate cancer risk, and vitamin E genetic variant data support this. By contrast, controlled vitamin E supplementation trials have had mixed results based on differing designs and dosages. Beta-carotene supplementation (in smokers) and higher circulating retinol and 25-hydroxy-vitamin D concentrations appear related to elevated prostate cancer risk. Our prospective metabolomic profiling of fasting serum collected 1-20 years prior to clinical diagnoses found reduced lipid and energy/TCA cycle metabolites, including inositol-1-phosphate, lysolipids, alpha-ketoglutarate, and citrate, significantly associated with lower risk of aggressive disease. Several active leads exist regarding the role of micronutrients and metabolites in prostate cancer carcinogenesis and risk. How vitamins D and A may adversely impact risk, and whether low-dose vitamin E supplementation remains a viable preventive approach, require further study.

Methods for prostate stabilization during transperineal LDR brachytherapy.

PubMed

Podder, Tarun; Sherman, Jason; Rubens, Deborah; Messing, Edward; Strang, John; Ng, Wan-Sing; Yu, Yan

2008-03-21

In traditional prostate brachytherapy procedures for a low-dose-rate (LDR) radiation seed implant, stabilizing needles are first inserted to provide some rigidity and support to the prostate. Ideally this will provide better seed placement and an overall improved treatment. However, there is much speculation regarding the effectiveness of using regular brachytherapy needles as stabilizers. In this study, we explored the efficacy of two types of needle geometries (regular brachytherapy needle and hooked needle) and several clinically feasible configurations of the stabilization needles. To understand and assess the prostate movement during seed implantation, we collected in vivo data from patients during actual brachytherapy procedures. In vitro experimentation with tissue-equivalent phantoms allowed us to further understand the mechanics behind prostate stabilization. We observed superior stabilization with the hooked needles compared to the regular brachytherapy needles (more than 40% in bilateral parallel needle configuration). Prostate movement was also reduced significantly when regular brachytherapy needles were in an angulated configuration as compared to the parallel configuration (more than 60%). When the hooked needles were angulated for stabilization, further reduction in prostate displacement was observed. In general, for convenience of dosimetric planning and to avoid needle collision, all needles are desired to be in a parallel configuration. In this configuration, hooked needles provide improved stabilization of the prostate. On the other hand, both regular and hooked needles appear to be equally effective in reducing prostate movement when they are in angulated configurations, which will be useful in seed implantation using a robotic system. We have developed nonlinear spring-damper model for the prostate movement which can be used for adapting dosimetric planning during brachytherapy as well as for developing more realistic haptic devices and

Isolation, purification and antioxidant activity of polysaccharides from the leaves of maca (Lepidium Meyenii).

PubMed

Caicai, Kang; Limin, Hao; Liming, Zhang; Zhiqiang, Zheng; Yongwu, Yang

2018-02-01

Two fractions of polysaccharides (MLP-1 and MLP-2) were extracted from the leaves of maca (Lepidium Meyenii Walp.) by water, and purified using DEAE-52 ion exchange resin and sephadex G-200 clumns chromatography. An investigation was carried out for their structural characterization and antioxidant activity in vitro. The results indicated that MLP-1 was mainly composed of ribose, rhamnose, arabinose, xylose, mannose, glucose and galactose, with the molar ratio of 0.12:0.32:1.50:0.32:1.03:1.00:0.93; the MLP-2 was a homopolysaccharide composed of glucose. The molecular weight (Mw) of MLP-1 was 42756Da, and the Mw of MLP-2 was 93541Da. The FT-IR spectra showed the general characteristic absorption peak of maca leaf polysaccharides (MLPs). The evaluation of antioxidant activity revealed that MLP-1 had strong scavenging effects in vitro on hydroxyl, superoxide anion and DPPH radicals, whose EC 50 (mg/mL) was 0.44, 0.21, and 0.82, respectively. Both MLP-1 and MLP-2 presented dose-dependently positive effects on the antioxidant-related parameters. The results suggested that the purified MLP-1 displayed better antioxidant capacities than that of MLP-1, which could be explored as potential antioxidant agents for the complementary medicine or functional foods. Copyright © 2017 Elsevier B.V. All rights reserved.

Potential efficacy of some african plants in benign prostatic hyperplasia and prostate cancer.

PubMed

Russo, Giorgio I; Cimino, Sebastiano; Salamone, Costanza; Madonia, Massimo; Favilla, Vincenzo; Castelli, Tommaso; Morgia, Giuseppe

2013-10-01

Traditional medicine is very popular in Africa and it is considered as an alternative form of health care. Plants and vegetables used in folk and traditional medicine have gained wide acceptance as one of the main sources of prophylactic and chemopreventive drug discovery and this is due to the evidence of particular biological and biochemical characteristics of each plants extracts. The role of these compounds in urological field may be explained by the antiinflammatory effect through interference with prostaglandin metabolism, alteration of lipid peroxidation, direct inhibition of prostate growth and moreover through an antiandrogenic or antiestrogenic effect and a decrease of the availability of sex hormone-binding globulin. Since Benign Prostatic Hyperplasia and Prostate Cancer are two of the most diffuse diseases of aging male and considering that standard medical therapy is accompanied with different side effects, the emerging use of African plants may be justified. This review takes a look at some African plants extracts properties and their relative urological application. Different biomolecular mechanisms of action are promising, suggesting a real application in reducing prostate cells proliferation.

A human prostatic bacterial isolate alters the prostatic microenvironment and accelerates prostate cancer progression.

PubMed

Simons, Brian W; Durham, Nicholas M; Bruno, Tullia C; Grosso, Joseph F; Schaeffer, Anthony J; Ross, Ashley E; Hurley, Paula J; Berman, David M; Drake, Charles G; Thumbikat, Praveen; Schaeffer, Edward M

2015-02-01

Inflammation is associated with several diseases of the prostate including benign enlargement and cancer, but a causal relationship has not been established. Our objective was to characterize the prostate inflammatory microenvironment after infection with a human prostate-derived bacterial strain and to determine the effect of inflammation on prostate cancer progression. To this end, we mimicked typical human prostate infection with retrograde urethral instillation of CP1, a human prostatic isolate of Escherichia coli. CP1 bacteria were tropic for the accessory sex glands and induced acute inflammation in the prostate and seminal vesicles, with chronic inflammation lasting at least 1 year. Compared to controls, infection induced both acute and chronic inflammation with epithelial hyperplasia, stromal hyperplasia, and inflammatory cell infiltrates. In areas of inflammation, epithelial proliferation and hyperplasia often persist, despite decreased expression of androgen receptor (AR). Inflammatory cells in the prostates of CP1-infected mice were characterized at 8 weeks post-infection by flow cytometry, which showed an increase in macrophages and lymphocytes, particularly Th17 cells. Inflammation was additionally assessed in the context of carcinogenesis. Multiplex cytokine profiles of inflamed prostates showed that distinct inflammatory cytokines were expressed during prostate inflammation and cancer, with a subset of cytokines synergistically increased during concurrent inflammation and cancer. Furthermore, CP1 infection in the Hi-Myc mouse model of prostate cancer accelerated the development of invasive prostate adenocarcinoma, with 70% more mice developing cancer by 4.5 months of age. This study provides direct evidence that prostate inflammation accelerates prostate cancer progression and gives insight into the microenvironment changes induced by inflammation that may accelerate tumour initiation or progression. Copyright © 2014 Pathological Society of Great

Benign Prostatic Hyperplasia: from Bench to Clinic

PubMed Central

Cho, Hee Ju

2012-01-01

Benign prostatic hyperplasia (BPH) is a prevalent disease, especially in old men, and often results in lower urinary tract symptoms (LUTS). This chronic disease has important care implications and financial risks to the health care system. LUTS are caused not only by mechanical prostatic obstruction but also by the dynamic component of obstruction. The exact etiology of BPH and its consequences, benign prostatic enlargement and benign prostatic obstruction, are not identified. Various theories concerning the causes of benign prostate enlargement and LUTS, such as metabolic syndrome, inflammation, growth factors, androgen receptor, epithelial-stromal interaction, and lifestyle, are discussed. Incomplete overlap of prostatic enlargement with symptoms and obstruction encourages focus on symptoms rather than prostate enlargement and the shifting from surgery to medicine as the treatment of BPH. Several alpha antagonists, including alfuzosin, doxazosin, tamsulosin, and terazosin, have shown excellent efficacy without severe adverse effects. In addition, new alpha antagonists, silodosin and naftopidil, and phosphodiesterase 5 inhibitors are emerging as BPH treatments. In surgical treatment, laser surgery such as photoselective vaporization of the prostate and holmium laser prostatectomy have been introduced to reduce complications and are used as alternatives to transurethral resection of the prostate (TURP) and open prostatectomy. The status of TURP as the gold standard treatment of BPH is still evolving. We review several preclinical and clinical studies about the etiology of BPH and treatment options. PMID:22468207

Prostate-Specific Antigen-Based Screening for Prostate Cancer: Evidence Report and Systematic Review for the US Preventive Services Task Force.

PubMed

Fenton, Joshua J; Weyrich, Meghan S; Durbin, Shauna; Liu, Yu; Bang, Heejung; Melnikow, Joy

2018-05-08

Prostate cancer is the second leading cause of cancer death among US men. To systematically review evidence on prostate-specific antigen (PSA)-based prostate cancer screening, treatments for localized prostate cancer, and prebiopsy risk calculators to inform the US Preventive Services Task Force. Searches of PubMed, EMBASE, Web of Science, and Cochrane Registries and Databases from July 1, 2011, through July 15, 2017, with a surveillance search on February 1, 2018. English-language reports of randomized clinical trials (RCTs) of screening; cohort studies reporting harms; RCTs and cohort studies of active localized cancer treatments vs conservative approaches (eg, active surveillance, watchful waiting); external validations of prebiopsy risk calculators to identify aggressive cancers. One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Prostate cancer and all-cause mortality; false-positive screening results, biopsy complications, overdiagnosis; adverse effects of active treatments. Random-effects meta-analyses were conducted for treatment harms. Sixty-three studies in 104 publications were included (N = 1 904 950). Randomization to PSA screening was not associated with reduced risk of prostate cancer mortality in either a US trial with substantial control group contamination (n = 76 683) or a UK trial with low adherence to a single PSA screen (n = 408 825) but was associated with significantly reduced prostate cancer mortality in a European trial (n = 162 243; relative risk [RR], 0.79 [95% CI, 0.69-0.91]; absolute risk reduction, 1.1 deaths per 10 000 person-years [95% CI, 0.5-1.8]). Of 61 604 men screened in the European trial, 17.8% received false-positive results. In 3 cohorts (n = 15 136), complications requiring hospitalization occurred in 0.5% to 1.6% of men undergoing biopsy after abnormal screening findings. Overdiagnosis was estimated to occur in 20.7% to 50

Combination of Autoantibody Signature with PSA Level Enables a Highly Accurate Blood-Based Differentiation of Prostate Cancer Patients from Patients with Benign Prostatic Hyperplasia.

PubMed

Leidinger, Petra; Keller, Andreas; Milchram, Lisa; Harz, Christian; Hart, Martin; Werth, Angelika; Lenhof, Hans-Peter; Weinhäusel, Andreas; Keck, Bastian; Wullich, Bernd; Ludwig, Nicole; Meese, Eckart

2015-01-01

Although an increased level of the prostate-specific antigen can be an indication for prostate cancer, other reasons often lead to a high rate of false positive results. Therefore, an additional serological screening of autoantibodies in patients' sera could improve the detection of prostate cancer. We performed protein macroarray screening with sera from 49 prostate cancer patients, 70 patients with benign prostatic hyperplasia and 28 healthy controls and compared the autoimmune response in those groups. We were able to distinguish prostate cancer patients from normal controls with an accuracy of 83.2%, patients with benign prostatic hyperplasia from normal controls with an accuracy of 86.0% and prostate cancer patients from patients with benign prostatic hyperplasia with an accuracy of 70.3%. Combining seroreactivity pattern with a PSA level of higher than 4.0 ng/ml this classification could be improved to an accuracy of 84.1%. For selected proteins we were able to confirm the differential expression by using luminex on 84 samples. We provide a minimally invasive serological method to reduce false positive results in detection of prostate cancer and according to PSA screening to distinguish men with prostate cancer from men with benign prostatic hyperplasia.

Comparison Between the Four-kallikrein Panel and Prostate Health Index for Predicting Prostate Cancer.

PubMed

Nordström, Tobias; Vickers, Andrew; Assel, Melissa; Lilja, Hans; Grönberg, Henrik; Eklund, Martin

2015-07-01

The four-kallikrein panel and the Prostate Health Index (PHI) have been shown to improve prediction of prostate cancer (PCa) compared with prostate-specific antigen (PSA). No comparison of the four-kallikrein panel and PHI has been presented. To compare the four-kallikrein panel and PHI for predicting PCa in an independent cohort. Participants were from a population-based cohort of PSA-tested men in Stockholm County. We included 531 men with PSA levels between 3 and 15 ng/ml undergoing first-time prostate biopsy during 2010-2012. Models were fitted to case status. We computed calibration curves, the area under the receiver-operating characteristics curve (AUC), decision curves, and percentage of saved biopsies. The four-kallikrein panel showed AUCs of 69.0 when predicting any-grade PCa and 71.8 when predicting high-grade cancer (Gleason score ≥7). Similar values were found for PHI: 70.4 and 71.1, respectively. Both models had higher AUCs than a base model with PSA value and age (p<0.0001 for both); differences between models were not significant. Sensitivity analyses including men with any PSA level or a previous biopsy did not materially affect our findings. Using 10% predicted risk of high-grade PCa by the four-kallikrein panel or PHI of 39 as cut-off for biopsy saved 29% of performed biopsies at a cost of delayed diagnosis for 10% of the men with high-grade cancers. Both models showed limited net benefit in decision analysis. The main study limitation was lack of digital rectal examination data and biopsy decision being based on PSA information. The four-kallikrein panel and PHI similarly improved discrimination when predicting PCa and high-grade PCa. Both are simple blood tests that can reduce the number of unnecessary biopsies compared with screening with total PSA, representing an important new option to reduce harm. Prostate-specific antigen screening is controversial due to limitations of the test. We found that two blood tests, the Prostate Health Index

Denosumab Reduces Risk of Bone Side Effects in Advanced Prostate Cancer

Cancer.gov

The biological agent denosumab (Xgeva) is more effective than zoledronic acid at decreasing the risk of bone fractures and other skeletal-related events (SRE) in men with castration-resistant metastatic prostate cancer, according to results from a randomi

Technological aspects of delivering cryotherapy for prostate cancer.

PubMed

Lau, Benjamin; Shah, Taimur Tariq; Valerio, Massimo; Hamid, Sami; Ahmed, Hashim Uddin; Arya, Manit

2015-03-01

Since the era of prostate specific antigen (PSA) testing, there has been a stage and grade migration seen with prostate cancer along with a reduction in mortality. Subsequently, concerns have been raised about the over treatment of patients following the diagnosis of localized prostate cancers. Cryotherapy, in which extremely low temperatures induce cell death via multiple mechanisms, has seen a drastic improvement in its technology since the 1800s. Such advances have improved oncological outcomes while reducing complication rates. Furthermore, technological advances have allowed the development of focal cryotherapy which aims to reduce morbidity associated with more radical whole-gland therapies. There is growing evidence that focal cryotherapy provides good oncological and morbidity rates when compared with traditional radical/whole-gland therapies.

Androgen Receptor Expression in Epithelial and Stromal Cells of Prostatic Carcinoma and Benign Prostatic Hyperplasia.

PubMed

Filipovski, Vanja; Kubelka-Sabit, Katerina; Jasar, Dzengis; Janevska, Vesna

2017-08-15

Prostatic carcinoma (PCa) derives from prostatic epithelial cells. However stromal microenvironment, associated with malignant epithelium, also plays a role in prostatic carcinogenesis. Alterations in prostatic stromal cells contribute to the loss of growth control in epithelial cells that lead to progression of PCa. To analyse the differences between Androgen Receptor (AR) expression in both epithelial and stromal cells in PCa and the surrounding benign prostatic hyperplasia (BPH) and to compare the results with tumour grade. Samples from 70 cases of radical prostatectomy specimens were used. The expression and intensity of the signal for AR was analysed in the epithelial and stromal cells of PCa and BPH, and the data was quantified using histological score (H-score). AR showed significantly lower expression in both epithelial and stromal cells of PCa compared to BPH. In PCa a significant positive correlation of AR expression was found between stromal and epithelial cells of PCa. AR expression showed a correlation between the stromal cells of PCa and tumour grade. AR expression is reduced in epithelial and stromal cells of PCa. Expression of AR in stromal cells of PCa significantly correlates with tumour grade.

A Specific Screening Strategy to Reduce Prostate Cancer Mortality

DTIC Science & Technology

2013-09-01

Vashaw Scientific, Norcross, GA ). Filter, camera, and image processing from the in vitro imaging methods were used in coordination with the...Cancer Facts and Figures 2011. (2011). American Cancer Society. Atlanta, GA . 2. Jemal, A, Siegel, R, Ward, E, Murray, T, Xu, J, Smigal, C, et al. (2006...overexpression in prostate cancer: relevance to tumor differentiation. Pathology oncology research : POR 15: 91-96. 11. Ouyang, XS , Wang, X, Lee, DT, Tsao, SW

A Neighborhood-Based Intervention to Reduce Prostate Cancer Disparities

DTIC Science & Technology

2016-10-01

computed. The total number of patients was 10,802. The median age was 65. Fifty-seven percent were married at diagnosis. The majority of...Hispanic patients were younger and less likely to be married compared to White patients. Tumor grade and stage were highest among Black patients...were more Black and unmarried . There was a higher percentage of high grade and high stage prostate cancer at diagnosis. There were fewer men, lower

Prostatic relaxation induced by agmatine is decreased in spontaneously hypertensive rats.

PubMed

Lee, Liang-Ming; Tsai, Tsung-Chin; Chung, Hsien-Hui; Tong, Yat-Ching; Cheng, Juei-Tang

2012-09-01

What's known on the subject? and What does the study add? Neurotransmitters are known to control prostate contractility. Agmatine is one of them and induces relaxation through imidazoline receptors. The paper shows that the action of agmatine is reduced in hypertensive rats, and that this change is related to the decrease of ATP-sensitive potassium channels in the prostate. The findings can increase our understanding of the possible underlying mechanism for the development of clinical benign prostatic hyperplasia. To compare agmatine-induced prostatic relaxation in hypertensive and control rats. To investigate the responsible mechanism(s) and the role of the ATP-sensitive potassium channel. Prostate strips were isolated from male spontaneously hypertensive (SH) rats and normal Wistar-Kyoto (WKY) rats for measurement of isometric tension. The strips were precontracted with 1 µmol/L phenylephrine or 50 mmol/L KCl. Dose-dependent relaxation of the prostatic strips was studied by cumulative administration of agmatine, 1 to 100 µmol/L, into the organ bath. Effects of specific antagonists on agmatine-induced relaxation were studied. Western blotting analysis was used to measure the gene expression of the ATP-sensitive potassium channel in the rat prostate. Prostatic relaxation induced by agmatine was markedly reduced in SH rats compared with WKY rats. The relaxation caused by agmatine was abolished by BU224, a selective imidazoline I(2)-receptor antagonist, but was not modified by efaroxan at a dose sufficient to block imidazoline I(1)-receptors. The relaxation induced by diazoxide at a concentration sufficient to activate ATP-sensitive potassium channels was markedly reduced in the SH rat prostate. Expressions of ATP-sensitive potassium channel sulphonylurea receptor and inwardly rectifying potassium channel (Kir) 6.2 subunits were both decreased in the prostate of SH rats. The decrease of agmatine-induced prostatic relaxation in SH rats is related to the change in

Lepidium meyenii (Maca) increases litter size in normal adult female mice

PubMed Central

Ruiz-Luna, Ana C; Salazar, Stephanie; Aspajo, Norma J; Rubio, Julio; Gasco, Manuel; Gonzales, Gustavo F

2005-01-01

Background Lepidium meyenii, known as Maca, grows exclusively in the Peruvian Andes over 4000 m altitude. It has been used traditionally to increase fertility. Previous scientific studies have demonstrated that Maca increases spermatogenesis and epididymal sperm count. The present study was aimed to investigate the effects of Maca on several fertility parameters of female mice at reproductive age. Methods Adult female Balb/C mice were divided at random into three main groups: i) Reproductive indexes group, ii) Implantation sites group and iii) Assessment of uterine weight in ovariectomized mice. Animals received an aqueous extract of lyophilized Yellow Maca (1 g/Kg BW) or vehicle orally as treatment. In the fertility indexes study, animals received the treatment before, during and after gestation. The fertility index, gestation index, post-natal viability index, weaning viability index and sex ratio were calculated. Sexual maturation was evaluated in the female pups by the vaginal opening (VO) day. In the implantation study, females were checked for implantation sites at gestation day 7 and the embryos were counted. In ovariectomized mice, the uterine weight was recorded at the end of treatment. Results Implantation sites were similar in mice treated with Maca and in controls. All reproductive indexes were similar in both groups of treatment. The number of pups per dam at birth and at postnatal day 4 was significantly higher in the group treated with Maca. VO day occurred earlier as litter size was smaller. Maca did not affect VO day. In ovariectomized mice, the treatment with Maca increased significantly the uterine weights in comparison to their respective control group. Conclusion Administration of aqueous extract of Yellow Maca to adult female mice increases the litter size. Moreover, this treatment increases the uterine weight in ovariectomized animals. Our study confirms for the first time some of the traditional uses of Maca to enhance female fertility. PMID

Lepidium meyenii (Maca) increases litter size in normal adult female mice.

PubMed

Ruiz-Luna, Ana C; Salazar, Stephanie; Aspajo, Norma J; Rubio, Julio; Gasco, Manuel; Gonzales, Gustavo F

2005-05-03

Lepidium meyenii, known as Maca, grows exclusively in the Peruvian Andes over 4000 m altitude. It has been used traditionally to increase fertility. Previous scientific studies have demonstrated that Maca increases spermatogenesis and epididymal sperm count. The present study was aimed to investigate the effects of Maca on several fertility parameters of female mice at reproductive age. Adult female Balb/C mice were divided at random into three main groups: i) Reproductive indexes group, ii) Implantation sites group and iii) Assessment of uterine weight in ovariectomized mice. Animals received an aqueous extract of lyophilized Yellow Maca (1 g/Kg BW) or vehicle orally as treatment. In the fertility indexes study, animals received the treatment before, during and after gestation. The fertility index, gestation index, post-natal viability index, weaning viability index and sex ratio were calculated. Sexual maturation was evaluated in the female pups by the vaginal opening (VO) day. In the implantation study, females were checked for implantation sites at gestation day 7 and the embryos were counted. In ovariectomized mice, the uterine weight was recorded at the end of treatment. Implantation sites were similar in mice treated with Maca and in controls. All reproductive indexes were similar in both groups of treatment. The number of pups per dam at birth and at postnatal day 4 was significantly higher in the group treated with Maca. VO day occurred earlier as litter size was smaller. Maca did not affect VO day. In ovariectomized mice, the treatment with Maca increased significantly the uterine weights in comparison to their respective control group. Administration of aqueous extract of Yellow Maca to adult female mice increases the litter size. Moreover, this treatment increases the uterine weight in ovariectomized animals. Our study confirms for the first time some of the traditional uses of Maca to enhance female fertility.

[Transrectal magnetotherapy of the prostate from Intramag device in prophylaxis of postoperative complications of transurethral resection of prostatic adenoma].

PubMed

Neĭmark, A I; Snegirev, I V; Neĭmark, B A

2006-01-01

The authors analyse preoperative preparation of 91 patients with benign prostatic hyperplasia (BPH). Two groups of patients received conventional preparation (group 1) and magnetotherapy (group 2) before TUR of the prostate. The examination covered immune system, bacteriological indices of urine and prostatic tissue. Infection of the urinary tract is a main risk factor of complications after TUR. Conventional preoperative preparation fails to correct immunity, to change bacterial urine flora, to improve hemodynamics in the prostate. Transrectal magnetotherapy with running magnetic field eliminates deficiency of T- and B-cell immunity, raises functional activity of B-lymphocytes and phagocytic ability of neutrophils, reduces endogenic intoxication, tissue edema, bacterial contamination, number of thrombohemorrhagic complications. This leads to a decrease in the number of postoperative complications.

Prostate cancer progression and mortality: a review of diet and lifestyle factors.

PubMed

Peisch, Sam F; Van Blarigan, Erin L; Chan, June M; Stampfer, Meir J; Kenfield, Stacey A

2017-06-01

To review and summarize evidence on the role of diet and lifestyle factors and prostate cancer progression, with a specific focus on habits after diagnosis and the risk of subsequent disease recurrence, progression, or death. Given the well-documented heterogeneity of prostate cancer and the long survivorship of the majority of diagnoses, our goal was to summarize and describe modifiable risk factors for clinically relevant prostate cancer. We focused where possible on epidemiologic studies of post-diagnostic habits and prostate cancer progression, defined as recurrence (e.g., PSA risk, secondary treatment), metastasis, or death. Where data were limited, we also describe evidence on risk factors and indicators of prostate cancer aggressiveness at diagnosis. A variety of dietary and lifestyle factors appear to affect prostate cancer progression. Several generally widely recommended lifestyle factors such as not smoking, maintaining a healthy body weight, and regular vigorous physical exercise also appear to affect prostate cancer progression. Several dietary factors, such as tomato sauce/lycopene, cruciferous vegetables, healthy sources of vegetable fats, and coffee, may also have a role in reducing risk of prostate cancer progression. Diet and lifestyle factors, in particular exercise and smoking cessation, may reduce the risk of prostate cancer progression and death. These promising findings warrant further investigation, as their overall impact might be large.

NADiA ProsVue prostate-specific antigen slope is an independent prognostic marker for identifying men at reduced risk of clinical recurrence of prostate cancer after radical prostatectomy.

PubMed

Moul, Judd W; Lilja, Hans; Semmes, O John; Lance, Raymond S; Vessella, Robert L; Fleisher, Martin; Mazzola, Clarisse; Sarno, Mark J; Stevens, Barbara; Klem, Robert E; McDermed, Jonathan E; Triebell, Melissa T; Adams, Thomas H

2012-12-01

To validate the hypothesis that men displaying serum prostate-specific antigen (PSA) slopes ≤ 2.0 pg/mL/mo after prostatectomy, measured using a new immuno-polymerase chain reaction diagnostic test (NADiA ProsVue), have a reduced risk of clinical recurrence as determined by positive biopsy, imaging findings, or death from prostate cancer. From 4 clinical sites, we selected a cohort of 304 men who had been followed up for 17.6 years after prostatectomy for clinical recurrence. We assessed the prognostic value of a PSA slope cutpoint of 2.0 pg/mL/mo against established risk factors to identify men at low risk of clinical recurrence using uni- and multivariate Cox proportional hazards regression and Kaplan-Meier analyses. The univariate hazard ratio of a PSA slope >2.0 pg/mL/mo was 18.3 (95% confidence interval 10.6-31.8) compared with a slope ≤ 2.0 pg/mL/mo (P <.0001). The median disease-free survival interval was 4.8 years vs >10 years in the 2 groups (P <.0001). The multivariate hazard ratio for PSA slope with the covariates of preprostatectomy PSA, pathologic stage, and Gleason score was 9.8 (95% confidence interval 5.4-17.8), an 89.8% risk reduction for men with PSA slopes ≤ 2.0 pg/mL/mo (P <.0001). The Gleason score (<7 vs ≥ 7) was the only other significant predictor (hazard ratio 5.4, 95% confidence interval 2.1-13.8, P = .0004). Clinical recurrence after radical prostatectomy is difficult to predict using established risk factors. We have demonstrated that a NADiA ProsVue PSA slope of ≤ 2.0 pg/mL/mo after prostatectomy is prognostic for a reduced risk of prostate cancer recurrence and adds predictive power to the established risk factors. Copyright © 2012 Elsevier Inc. All rights reserved.

Oncogenic LINE-1 Retroelements Sustain Prostate Tumor Cells and Promote Metastatic Progression

DTIC Science & Technology

2015-10-01

elements in prostate cancer contribute to its progression by activating oncogenic DNA sequences, or silencing tumor suppressor like sequences. We have...prostate cancer cells. Experiments are ongoing to determine if PIWIL-1 expression in prostate cancer cells will reduce their growth, thereby providing...proof of principle for future gene-based therapeutics for this cancer . 15. SUBJECT TERMS Prostate cancer , LINE-1, PIWIL-1, retrotransposons 16

Ejaculatory Function After Permanent {sup 125}I Prostate Brachytherapy for Localized Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huyghe, Eric; Department of Urology and Andrology, Paul Sabatier University, CHU Paule de Viguier, Toulouse; Delannes, Martine

Purpose: Ejaculatory function is an underreported aspect of male sexuality in men treated for prostate cancer. We conducted the first detailed analysis of ejaculatory function in patients treated with permanent {sup 125}I prostate brachytherapy for localized prostate cancer. Patients and Methods: Of 270 sexually active men with localized prostate cancer treated with permanent {sup 125}I prostate brachytherapy, 241 (89%), with a mean age of 65 years (range, 43-80), responded to a mailed questionnaire derived from the Male Sexual Health Questionnaire regarding ejaculatory function. Five aspects of ejaculatory function were examined: frequency, volume, dry ejaculation, pleasure, and pain. Results: Of themore » 241 sexually active men, 81.3% had conserved ejaculatory function after prostate brachytherapy; however, the number of patients with rare/absent ejaculatory function was double the pretreatment number (p < .0001). The latter finding was correlated with age (p < .001) and the preimplant International Index of Erectile Function score (p < .001). However, 84.9% of patients with maintained ejaculatory function after implantation reported a reduced volume of ejaculate compared with 26.9% before (p < .001), with dry ejaculation accounting for 18.7% of these cases. After treatment, 30.3% of the patients experienced painful ejaculation compared with 12.9% before (p = .0001), and this was associated with a greater number of implanted needles (p = .021) and the existence of painful ejaculation before implantation (p < .0001). After implantation, 10% of patients who continued to be sexually active experienced no orgasm compared with only 1% before treatment. in addition, more patients experienced late/difficult or weak orgasms (p = .001). Conclusion: Most men treated with brachytherapy have conserved ejaculatory function after prostate brachytherapy. However, most of these men experience a reduction in volume and a deterioration in orgasm.« less

Impact of PSA density of transition zone as a potential parameter in reducing the number of unnecessary prostate biopsies in patients with psa levels between 2.6 and 10.0 ng/mL.

PubMed

Castro, Hugo A Socrates; Iared, Wagner; Santos, José Eduardo Mourão; Solha, Raphael Sandes; Shigueoka, David Carlos; Ajzen, Sergio Aron

2018-04-10

To assess the accuracy of prostate-specific antigen (PSA) adjusted for the transition zone volume (PSATZ) in predicting prostate cancer by comparing the ability of several PSA parameters in predicting prostate cancer in men with intermediate PSA levels of 2.6 - 10.0 ng/mL and its ability to reduce unnecessary biopsies. This study included 656 patients referred for prostate biopsy who had a serum PSA of 2.6 - 10.0 ng/mL. Total prostate and transition zone volumes were measured by transrectal ultrasound using the prolate ellipsoid method. The clinical values of PSA, free-to-total (F/T) ratio, PSA density (PSAD) and PSATZ for the detection of prostate cancer were calculated and statistical comparisons between biopsy-positive (cancer) and biopsy-negative (benign) were conducted. Cancer was detected in 172 patients (26.2%). Mean PSA, PSATZ, PSAD and F/T ratio were 7.5 ng/mL, 0.68 ng/mL/cc. 0.25 ng/mL/cc and 0.14 in patients with prostate cancer and 6.29 ng/mL, 0.30 ng/mL/cc, 0.16 ng/mL/cc and 0.22 in patients with benign biopsies, respectively. ROC curves analysis demonstrated that PSATZ had a higher area under curve (0,838) than F/T ratio (0,806) (P<0.001) and PSAD (0,806) (P<0.001). With a cut-off value of 0.22 ng/mL/cc, PSATZ had 100% of sensitivity and could have prevented 24% of unnecessary biopsies. PSATZ may be useful in enhancing the specificity of serum PSA. Compared to other PSA related parameters, it was better in differentiating between prostate cancer and benign prostatic enlargement. Also, PSATZ could reduce a significant number of unnecessary biopsies. Copyright® by the International Brazilian Journal of Urology.

Prostate cancer

MedlinePlus

... of prostate cancer. But, it can increase your prostate-specific antigen (PSA) blood test result. Symptoms With early prostate ... 2009 Best Practice Statement. www.auanet.org/guidelines/prostate-specific-antigen-(2009-amended-2013) . Accessed October 9, 2017. Moyer ...

Update on cryotherapy for localized prostate cancer.

PubMed

Ritch, Chad R; Katz, Aaron E

2009-05-01

Stage migration has led to an increased incidence of localized and low-risk prostate cancer. Intermediate-term data are emerging on the efficacy of cryotherapy, but direct comparison to other therapeutic modalities is difficult as the parameters for recurrence are not well defined. Studies using the American Society for Therapeutic Radiation and Oncology and the Phoenix (nadir plus 2) criteria for biochemical recurrence show that primary cryotherapy appears to be comparable for low-risk prostate cancer as other treatment modalities. In addition, health-related quality-of-life measures have improved with the most recent third-generation systems demonstrating low incontinence and urethrorectal fistula rates. Erectile dysfunction is high with whole gland ablation, but focal therapy may reduce these rates while still ablating unilateral cancerous tissue. Prostate cryotherapy for localized prostate cancer is an evolving but viable therapeutic option. Long-term data are still needed to establish a definitive role for cryosurgery in prostate cancer treatment.

Prostate-specific antigen velocity is not better than total prostate-specific antigen in predicting prostate biopsy diagnosis.

PubMed

Gorday, William; Sadrzadeh, Hossein; de Koning, Lawrence; Naugler, Christopher T

2015-12-01

1.) Identify whether prostate-specific antigen velocity improves the ability to predict prostate biopsy diagnosis. 2.) Test whether there is an increase in the predictive capability of models when Gleason 7 prostate cancers are separated into a 3+4 and a 4+3 group. Calgary Laboratory Services' Clinical Laboratory Information System was searched for prostate biopsies reported between January 1, 2009 and December 31, 2013. Total prostate-specific antigen tests were recorded for each patient from January 1, 2007 to the most recent test before their recorded prostate biopsy. The data set was divided into the following three groups for comparison; benign, all prostate cancer and Gleason 7-10. The Gleason grade 7-10 group was further divided into 4+3 and 3+4 Gleason 7 prostate cancers. Prostate-specific antigen velocity was calculated using four different methods found in the literature. Receiver operator curves were used to assess operational characteristics of the tests. 4622 men between the ages of 40-89 with a prostate biopsy were included for analysis. Combining prostate-specific antigen velocity with total prostate-specific antigen (AUC=0.570-0.712) resulted in small non-statistically significant changes to the area under the curve compared to the area under the curve of total prostate-specific antigen alone (AUC=0.572-0.699). There were marked increases in the area under curves when 3+4 and 4+3 Gleason 7 cancers were separated. Prostate-specific antigen velocity does not add predictive value for prostate biopsy diagnosis. The clinical significance of the prostate specific antigen test can be improved by separating Gleason 7 prostate cancers into a 3+4 and 4+3 group. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Targeting the prostate for destruction through a vascular address

PubMed Central

Arap, Wadih; Haedicke, Wolfgang; Bernasconi, Michele; Kain, Renate; Rajotte, Daniel; Krajewski, Stanislaw; Ellerby, H. Michael; Bredesen, Dale E.; Pasqualini, Renata; Ruoslahti, Erkki

2002-01-01

Organ specific drug targeting was explored in mice as a possible alternative to surgery to treat prostate diseases. Peptides that specifically recognize the vasculature in the prostate were identified from phage-displayed peptide libraries by selecting for phage capable of homing into the prostate after an i.v. injection. One of the phage selected in this manner homed to the prostate 10–15 times more than to other organs. Unselected phage did not show this preference. The phage bound also to vasculature in the human prostate. The peptide displayed by the prostate-homing phage, SMSIARL (single letter code), was synthesized and shown to inhibit the homing of the phage when co-injected into mice with the phage. Systemic treatment of mice with a chimeric peptide consisting of the SMSIARL homing peptide, linked to a proapoptotic peptide that disrupts mitochondrial membranes, caused tissue destruction in the prostate, but not in other organs. The chimeric peptide delayed the development of the cancers in prostate cancer-prone transgenic mice (TRAMP mice). These results suggest that it may be possible to develop an alternative to surgical prostate resection and that such a treatment may also reduce future cancer risk. PMID:11830668

DNA Methyl Transferase 1 Reduces Expression of SRD5A2 in the Aging Adult Prostate

PubMed Central

Ge, Rongbin; Wang, Zongwei; Bechis, Seth K.; Otsetov, Alexander G.; Hua, Shengyu; Wu, Shulin; Wu, Chin-Lee; Tabatabaei, Shahin; Olumi, Aria F.

2016-01-01

5-α Reductase type 2 (SRD5A2) is a critical enzyme for prostatic development and growth. Inhibition of SRD5A2 by finasteride is used commonly for the management of urinary obstruction caused by benign prostatic hyperplasia. Contrary to common belief, we have found that expression of SRD5A2 is variable and absent in one third of benign adult prostates. In human samples, absent SRD5A2 expression is associated with hypermethylation of the SRD5A2 promoter, and in vitro SRD5A2 promoter activity is suppressed by methylation. We show that methylation of SRD5A2 is regulated by DNA methyltransferase 1, and inflammatory mediators such as tumor necrosis factor α, NF-κB, and IL-6 regulate DNA methyltransferase 1 expression and thereby affect SRD5A2 promoter methylation and gene expression. Furthermore, we show that increasing age in mice and humans is associated with increased methylation of the SRD5A2 promoter and concomitantly decreased protein expression. Artificial induction of inflammation in prostate primary epithelial cells leads to hypermethylation of the SRD5A2 promoter and silencing of SRD5A2, whereas inhibition with tumor necrosis factor α inhibitor reactivates SRD5A2 expression. Therefore, expression of SRD5A2 is not static and ubiquitous in benign adult prostate tissues. Methylation and expression of SRD5A2 may be used as a gene signature to tailor therapies for more effective treatment of prostatic diseases. PMID:25700986

Epidemiology of prostatitis

PubMed Central

Krieger, John N.; Lee, Shaun Wen Huey; Jeon, Jeonseong; Cheah, Phaik Yeong; Liong, Men Long; Riley, Donald E.

2008-01-01

Background Prostatitis describes a combination of infectious diseases (acute and chronic bacterial prostatitis), chronic pelvic pain syndrome, and asymptomatic inflammation. Materials and methods We employed evidence-based methods to review the epidemiology of prostatitis syndromes. Results The prevalence of prostatitis symptoms could be compared in five studies surveying 10 617 men. Overall, 873 participants met various criteria for prostatitis, representing an overall rate of 8.2%, with prevalence ranging from 2.2 to 9.7%. A history of sexually transmitted diseases was associated with an increased risk for prostatitis symptoms. Men reporting a history of prostatitis symptoms had a substantially increased rate of benign prostatic hyperplasia, lower urinary tract symptoms and prostate cancer. In one study, the incidence of physician-diagnosed prostatitis was 4.9 cases per 1000 person-years. Two studies suggest that about one-third of men reporting prostatitis symptoms had resolution after 1 year. Patients with previous episodes and more severe symptoms are at higher risk for chronic pelvic pain. Discussion The prevalence of prostatitis symptoms is high, comparable to rates of ischamic heart disease and diabetes. Clinical evaluation appears necessary to verify that prostatitis is responsible for patients’ symptoms. Prostatitis symptoms may increase a man’s risk for benign prostate hypertrophy, lower urinary tract symptoms and prostate cancer. We need to define natural history and consequences of prostatitis, develop better algorithms for diagnosis and treatment, and develop strategies for prevention. PMID:18164907

Benign prostatic hyperplasia.

PubMed

Chughtai, Bilal; Forde, James C; Thomas, Dominique Dana Marie; Laor, Leanna; Hossack, Tania; Woo, Henry H; Te, Alexis E; Kaplan, Steven A

2016-05-05

Benign prostatic hyperplasia (BPH), which causes lower urinary tract symptoms (LUTS), is a common diagnosis among the ageing male population with increasing prevalence. Many risks factors, both modifiable and non-modifiable, can increase the risk of development and progression of BPH and LUTS. The symptoms can be obstructive (resulting in urinary hesitancy, weak stream, straining or prolonged voiding) or irritative (resulting in increased urinary frequency and urgency, nocturia, urge incontinence and reduced voiding volumes), or can affect the patient after micturition (for example, postvoid dribble or incomplete emptying). BPH occurs when both stromal and epithelial cells of the prostate in the transitional zone proliferate by processes that are thought to be influenced by inflammation and sex hormones, causing prostate enlargement. Patients with LUTS undergo several key diagnostic investigations before being diagnosed with BPH. Treatment options for men with BPH start at watchful waiting and progress through medical to surgical interventions. For the majority of patients, the starting point on the treatment pathway will be dictated by their symptoms and degree of bother.

Metabolomic differentiation of maca (Lepidium meyenii) accessions cultivated under different conditions using NMR and chemometric analysis.

PubMed

Zhao, Jianping; Avula, Bharathi; Chan, Michael; Clément, Céline; Kreuzer, Michael; Khan, Ikhlas A

2012-01-01

To gain insights on the effects of color type, cultivation history, and growing site on the composition alterations of maca (Lepidium meyenii Walpers) hypocotyls, NMR profiling combined with chemometric analysis was applied to investigate the metabolite variability in different maca accessions. Maca hypocotyls with different colors (yellow, pink, violet, and lead-colored) cultivated at different geographic sites and different areas were examined for differences in metabolite expression. Differentiations of the maca accessions grown under the different cultivation conditions were determined by principle component analyses (PCAs) which were performed on the datasets derived from their ¹H NMR spectra. A total of 16 metabolites were identified by NMR analysis, and the changes in metabolite levels in relation to the color types and growing conditions of maca hypocotyls were evaluated using univariate statistical analysis. In addition, the changes of the correlation pattern among the metabolites identified in the maca accessions planted at the two different sites were examined. The results from both multivariate and univariate analysis indicated that the planting site was the major determining factor with regards to metabolite variations in maca hypocotyls, while the color of maca accession seems to be of minor importance in this respect. © Georg Thieme Verlag KG Stuttgart · New York.

Feeding hydroalcoholic extract powder of Lepidium meyenii (maca) enhances testicular gene expression of 3β-hydroxysteroid dehydrogenase in rats.

PubMed

Ohta, Y; Kawate, N; Inaba, T; Morii, H; Takahashi, K; Tamada, H

2017-12-01

Although feeding diets containing the extract powder of Lepidium meyenii (maca), a plant growing in Peru's Central Andes, increases serum testosterone concentration associated with enhanced ability of testosterone production by Leydig cells in male rats, changes in testicular steroidogenesis-related factors by the maca treatment are not known. This study examined the effects of maca on testicular gene expressions for luteinizing hormone receptor, steroidogenic acute regulatory protein and steroidogenic enzymes. Eight-week-old male rats were given the diets with or without (control) the maca extract powder (2%) for 6 weeks, and mRNA levels were determined by reverse transcription quantitative real-time PCR. The results showed that the testicular mRNA level of HSD3B1 (3β-hydroxysteroid dehydrogenase; 3β-HSD) increased by the treatment, whereas the levels of the other factors examined did not change. These results suggest that increased expression of 3β-HSD gene may be involved in the enhanced steroidogenic ability by the maca treatment in rat testes. © 2017 Blackwell Verlag GmbH.

Antioxidant Prophylaxis in the Prevention of Prostatic Epithelial Neoplasia

DTIC Science & Technology

2009-02-01

of antioxidants such as selenium, tocopherols , lycopene, β-carotene etc. have been found to be effective in lowering prostate cancer risk. Although...3ng/ml; 2). The α- tocopherol , β-carotene (ATBC) cancer prevention trial in Finland found that consumption of vitamin E reduced clinical prostate

Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids.

PubMed

Karandish, Fataneh; Haldar, Manas K; You, Seungyong; Brooks, Amanda E; Brooks, Benjamin D; Guo, Bin; Choi, Yongki; Mallik, Sanku

2016-11-30

Prostate cancer cells overexpress the prostate-specific membrane antigen (PSMA) receptors on the surface. Targeting the PSMA receptor creates a unique opportunity for drug delivery. Docetaxel is a Food and Drug Administration-approved drug for treating metastatic and androgen-independent prostate cancer, and mocetinostat is a potent inhibitor of class I histone deacetylases. In this study, we prepared reduction-sensitive polymersomes presenting folic acid on the surface and encapsulating either docetaxel or mocetinostat. The presence of folic acid allowed efficient targeting of the PSMA receptor and subsequent internalization of the polymeric vesicles in cultured LNCaP prostate cancer cell spheroids. The intracellular reducing agents efficiently released docetaxel and mocetinostat from the polymersomes. The combination of the two drug-encapsulated polymersome formulations significantly ( p < 0.05) decreased the viability of the LNCaP cells (compared to free drugs or control) in three-dimensional spheroid cultures. The calculated combination index value indicated a synergistic effect for the combination of mocetinostat and docetaxel. Thus, our PSMA-targeted drug-encapsulated polymersomes has the potential to lead to a new direction in prostate cancer therapy that decreases the toxicity and increases the efficacy of the drug delivery systems.

Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids

PubMed Central

2016-01-01

Prostate cancer cells overexpress the prostate-specific membrane antigen (PSMA) receptors on the surface. Targeting the PSMA receptor creates a unique opportunity for drug delivery. Docetaxel is a Food and Drug Administration-approved drug for treating metastatic and androgen-independent prostate cancer, and mocetinostat is a potent inhibitor of class I histone deacetylases. In this study, we prepared reduction-sensitive polymersomes presenting folic acid on the surface and encapsulating either docetaxel or mocetinostat. The presence of folic acid allowed efficient targeting of the PSMA receptor and subsequent internalization of the polymeric vesicles in cultured LNCaP prostate cancer cell spheroids. The intracellular reducing agents efficiently released docetaxel and mocetinostat from the polymersomes. The combination of the two drug-encapsulated polymersome formulations significantly (p < 0.05) decreased the viability of the LNCaP cells (compared to free drugs or control) in three-dimensional spheroid cultures. The calculated combination index value indicated a synergistic effect for the combination of mocetinostat and docetaxel. Thus, our PSMA-targeted drug-encapsulated polymersomes has the potential to lead to a new direction in prostate cancer therapy that decreases the toxicity and increases the efficacy of the drug delivery systems. PMID:27917408

Losartan sensitizes selectively prostate cancer cell to ionizing radiation.

PubMed

Yazdannejat, H; Hosseinimehr, S J; Ghasemi, A; Pourfallah, T A; Rafiei, A

2016-01-11

Losartan is an angiotensin II receptor (AT-II-R) blocker that is widely used by human for blood pressure regulation. Also, it has antitumor property. In this study, we investigated the radiosensitizing effect of losartan on cellular toxicity induced by ionizing radiation on prostate cancer and non-malignant fibroblast cells. Human prostate cancer (DU-145) and human non-malignant fibroblast cells (HFFF2) were treated with losartan at different concentrations (0.5, 1, 10, 50 and 100 µM) and then these cells were exposed to ionizing radiation. The cell proliferation was determined using MTT assay. Our results showed that losartan exhibited antitumor effect on prostate cancer cells; it was reduced cell survival to 66% at concentration 1 µM. Losartan showed an additive killing effect in combination with ionizing radiation on prostate cancer cell. The cell proliferation was reduced to 54% in the prostate cancer cells treated with losartan at concentration 1 µM in combination with ionizing radiation. Losartan did not exhibit any toxicity on HFFF2 cell. This result shows a promising effect of losartan on enhancement of therapeutic effect of ionizing radiation in patients during therapy.

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer.

PubMed

Rybicki, B A; Kryvenko, O N; Wang, Y; Jankowski, M; Trudeau, S; Chitale, D A; Gupta, N S; Rundle, A; Tang, D

2016-06-01

Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I-III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR)=0.47; 95% confidence interval (CI)=0.27-0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR=3.56; 95% CI=1.15-10.99). Moreover, PSA velocity (P=0.008) and frequency of PSA testing (P=0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR=2.97; 95% CI=1.40-6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR=1.91; 95% CI=1.09-3.35). In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was modified by histological prostatic inflammation, PSA velocity, and

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer

PubMed Central

Rybicki, BA; Kryvenko, ON; Wang, Y; Jankowski, M; Trudeau, S; Chitale, DA; Gupta, NS; Rundle, A; Tang, D

2016-01-01

BACKGROUND Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. METHODS Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I–III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). RESULTS Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR) = 0.47; 95% confidence interval (CI) = 0.27–0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR = 3.56; 95% CI = 1.15–10.99). Moreover, PSA velocity (P = 0.008) and frequency of PSA testing (P = 0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR = 2.97; 95% CI = 1.40–6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR = 1.91; 95% CI = 1.09–3.35). CONCLUSIONS In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was

Perinatal exposure to mixtures of anti-androgenic chemicals causes proliferative lesions in rat prostate.

PubMed

Boberg, Julie; Johansson, Hanna K L; Hadrup, Niels; Dreisig, Karin; Berthelsen, Line; Almstrup, Kristian; Vinggaard, Anne Marie; Hass, Ulla

2015-02-01

Elevated levels of endogenous or exogenous estrogens during fetal life can induce permanent disturbances in prostate growth and predispose to precancerous lesions. Recent studies have indicated that also early anti-androgen exposure may affect prostate cancer risk. We examined the influence of perinatal exposure to mixtures of anti-androgenic and estrogenic chemicals on prostate development. Wistar rats were exposed from gestation day 7 to postnatal day 22 to a mixture of 8 anti-androgenic compounds (AAMix), a mixture of four estrogenic compounds (EMix), or paracetamol or a mixture of all 13 compounds (TotalMix) in mixture ratios reflecting human exposure levels. Ventral prostate weights were reduced by the TotalMix and AAMix in pre-pubertal rats. Histological changes in prostate appeared with increasing age and indicated a shift from the normal age-dependent epithelial atrophy towards hyperplasia. These lesions showed similarities to pre-cancerous lesions in humans. Increased proliferation was observed already in pre-puberty and it was hypothesized that this could be associated with reduced ERβ signaling, but no clear conclusions could be made from gene expression studies on ERβ-related pathways. The influences of the estrogenic chemicals and paracetamol on prostate morphology were minor, but in young adulthood the estrogen mixture reduced ventral prostate mRNA levels of Igf1 and paracetamol reduced the mRNA level ofPbpc3. Mixtures of endocrine disrupters relevant for human exposure was found to elicit persistent effects on the rat prostate following perinatal exposure, suggesting that human perinatal exposure to environmental chemicals may increase the risk of prostate cancer later in life. © 2014 Wiley Periodicals, Inc.

New Bacterial Infection in the Prostate after Transrectal Prostate Biopsy.

PubMed

Seo, Yumi; Lee, Gilho

2018-04-23

The prostate is prone to infections. Hypothetically, bacteria can be inoculated into the prostate during a transrectal prostate biopsy (TRPB) and progress into chronic bacterial prostatitis. Therefore, we examined new bacterial infections in biopsied prostates after TRPB and whether they affect clinical characteristics in the biopsied patients. Of men whose prostate cultures have been taken prior to TRPB, 105 men with bacteria-free benign prostate pathology underwent an additional repeated prostate culture within a year after TRPB. Twenty out of 105 men (19.05%) acquired new bacteria in their naïve prostates after TRPB. Except for one single case of Escherichia coli infection, 19 men had acquired gram-positive bacteria species. Between the culture-positive and negative groups, there were no significant differences in age, serum prostate-specific antigen (PSA) level, white blood cell (WBC) counts in expressed prostatic secretion (EPS), prostate volume, symptom severities in Korean version of the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) questionnaire, and patient-specific risk factors for biopsy associated infectious complications. Additionally, the TRPB procedure increased the WBC counts in post-biopsy EPS ( P = 0.031, McNemar test), but did not increase the serum PSA level and symptoms of NIH-CPSI in 20 men who acquired new bacteria after TRPB. The TRPB procedure was significantly associated with acquiring new bacterial infections in the biopsied prostate, but these localized bacteria did not affect patients' serum PSA level and symptoms after biopsy.

Effect of ethanolic extract of Lepidium meyenii Walp on serum hormone levels in ovariectomized rats.

PubMed

Zhang, Yongzhong; Yu, Longjiang; Jin, Wenwen; Ao, Mingzhang

2014-01-01

To evaluate the effect of long-term ethanol extract of Lepidium meyenii (Maca) on serum hormone levels in ovariectomized (OVX) rats and compare them with the effect of diethylstilbestrol. Fifty female Sprague-Dawley rats were ovariectomized or sham operated. Both sham and OVX control groups (n = 10, respectively) received the vehicle. The remaining OVX rats were oral administrated with ethanol extract of Maca (0.096, or 0.24g/kg; n = 10, respectively) and diethylstilbestrol (0.05 mg/kg; n = 10). The treatment continued for 28 weeks. At week 12 and week 28, the blood of rats was collected and serum hormone levels, including estradiol (E2), testosterone (T) and follicle-stimulating hormone (FSH) were measured by radioimmunoassay. At week 12, the levels of serum E2 were slightly higher in Maca groups than that in OVX group; T levels were significantly decreased; and FSH levels were advanced slightly in Maca groups than that in sham group. After 28 weeks administration, serum E2 levels in Maca-treated animals did not differ significantly from sham control, the low dose of Maca increased serum E2 levels, and Maca prevented increase in serum FSH levels compared with OVX group. Long-term Maca supply modulates endocrine hormone balance in OVX rats, especially it decreases enhanced FSH levels. It is proposed that Maca may become a potential choice for postmenopausal women.

Does prolonged anti-inflammatory therapy reduce number of unnecessary repeat saturation prostate biopsy?

PubMed

Candiano, Giuseppe; Pepe, Pietro; Pietropaolo, Francesco; Aragona, Francesco

2013-06-24

The effect of a prolonged oral anti-inflammatory therapy on PSA values in patients with persistent abnormal PSA values after negative prostate biopsy (PBx) was evaluated. From September 2011 to September 2012, 70 patients (medi- an age 62 years), with persistent abnormal PSA values after negative extended PBx, were given an herbal extract with anti-inflammatory activity for 3 months (Lenidase®; 1 tablet daily constituted of baicalina, bromelina and escina). All patients were submitted to prostate biopsy for: abnormal DRE; PSA > 10 ng/mL, PSA values between 4.1-10 or 2.6-4 ng/mL with free/total PSA < 25% and < 20%, respectively. Three months after the end of anti-inflammato- ry therapy all patients were revaluated; indication for repeat saturation biopsy (SPBx) and detection rate for PCa were compared with those previously recorded in our Department using the same inclusions criteria for biopsy. Oral administration of Lenidase® was well tolerated and no side effects were observed; PSA values decreased in 54 (77.8%) out 70 patients with a median PSA reduction of 20.5% (from 8.8 to 7 ng/mL) and remained unchanged in 16 patients (22.2%); the repeat SPBx rate resulted significantly lower (22.8% vs 35.5%; p < 0.05) showing a superimposable detection rate for PCa (3 cases) in comparison with our previous data (18.7% vs 22%). In our preliminary data a prolonged oral anti-inflammatory therapy reduced PSA levels in patients with negative PBx and persistent suspicious for PCa decreasing the indication to perform repeat SPBx (about 30% of the cases).

The Mediterranean Diet Reduces the Risk and Mortality of the Prostate Cancer: A Narrative Review

PubMed Central

Capurso, Cristiano; Vendemiale, Gianluigi

2017-01-01

Prostate cancer is the second most common cancer in the world among men, and is the fifth most common cause of cancer death among men. The aim of our review was to analyze observational and case–control studies to point out the effects of overweight and diets components on the cancer risk, particularly on risk of prostate cancer, and the effect of the Mediterranean diet (MD) on the reduction of risk and mortality of prostate cancer. It is known that incidence and progression of cancer is multifactorial. Cancer of the large bowel, breast, endometrium, and prostate are due also to a high body mass index and to high consumption of high carcinogenic dietary factors, as red and processed meat or saturated fats rich foods, and to a low consumption of vegetables and fruits. Previous meta-analysis suggested that high adherence to diet model based on the traditional MD pattern gives a significant protection from incidence and mortality of cancer of all types. The main component of the MD is olive oil, consumed in high amount by Mediterranean basin populations. In addition, phenolic compounds exert some strong chemo-preventive effects, which are due to several mechanisms, including both antioxidant effects and actions on cancer cell signaling and cell cycle progression and proliferation. The protective effect of the MD against the prostate cancer is also due to the high consumption of tomato sauce. Lycopene is the most relevant functional component in tomatoes; after activating by the cooking of tomato sauce, it exerts antioxidant properties by acting in the modulation of downregulation mechanisms of the inflammatory response. MD, therefore, represents a healthy dietary pattern in the context of a healthy lifestyle habits. In conclusion, our narrative review allows us to reaffirm how nutritional factors play an important role in cancer initiation and development, and how a healthy dietary pattern represented by MD and its components, especially olive oil, could exert a

Understanding Prostate Changes

Cancer.gov

Prostate changes and symptoms that are not cancer. Learn about symptoms, risk factors, and treatment for prostatitis, enlarged prostate (BPH), prostate cancer. Talk with doctor about prostate cancer screening tests (DRE, PSA), biopsy, and Gleason score.

Longitudinal Association between Prostatitis and Development of Benign Prostatic Hyperplasia

PubMed Central

St. Sauver, Jennifer L.; Jacobson, Debra J.; McGree, Michaela E.; Girman, Cynthia J.; Lieber, Michael M.; Jacobsen, Steven J.

2008-01-01

OBJECTIVES To determine whether physician-diagnosed prostatitis was associated with later development of development of BPH-associated events in a longitudinal, population-based sample of 2447 men residing in Olmsted County, Minnesota. METHODS Medical records were reviewed for physician diagnosis of prostatitis and subsequent diagnoses of BPH, enlarged prostate, prostatism, and acute urinary retention. Records were also reviewed for medical or surgical treatments for BPH. Odds ratios were calculated to assess the associations between physician-diagnosed prostatitis and later development of development of BPH-associated events. RESULTS Physician-diagnosed prostatitis was associated with a 2.4-fold increased odds of receiving a later diagnosis of prostatism, enlarged prostate, or BPH (OR: 2.44, 95% CI: 1.48, 4.01). Prostatitis was also associated with a 70% increased odds of requiring later treatment for BPH (OR: 1.69, 95% CI: 1.28, 2.22), and a non-significant increased odds of acute urinary retention (OR: 1.33, 95% CI: 0.89, 1.99). CONCLUSIONS Physician-diagnosed prostatitis was associated with an increased risk of later onset of several BPH-associated events. Physician-diagnosed prostatitis may therefore be an early marker or a risk factor for development of later prostatic or urologic problems. PMID:18342190

[Correlation of IL-8 and IL-6 in prostatic fluid with serum prostate-specific antigen level in patients with benign prostatic hyperplasia complicated by prostatitis].

PubMed

Ren, Xingfei; Wu, Chunlei; Yu, Qinnan; Zhu, Feng; Liu, Pei; Zhang, Huiqing

2016-01-01

To investigate the correlation of the levels of interleukin-8 (IL-8) and IL-6 in the prostatic fluid with serum levels of serum prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH) complicated by prostatitis. A series of 211 patients undergoing surgery of BPH were divided into BPH group (n=75) and BPH with prostatitis group (n=136) according to the white blood cell count in the prostatic fluid. The clinical and laboratory findings were compared between the two groups, and stepwise regression analysis was used to assess the association of IL-8 and IL-6 with serum PSA level. No significant differences were found in age, BMI, blood pressure, blood glucose, blood lipids, IPSS score, PSA-Ratio, or prostate volume between the two groups (P<0.05). The patients with prostatitis had significantly increased serum PSA and prostate fluid IL-8 and IL-6 levels compared with those without prostatitis (P<0.001). Multiple linear regression analysis showed that IL-8 and IL-6 levels and white blood cell count in the prostatic fluid were all positively correlated with serum PSA level. Prostatitis is an important risk factor for elevated serum PSA level in patients with BPH, and both IL-8 and IL-6 levels in the prostatic fluid are correlated with serum PSA level.

Magnetic resonance spectroscopic imaging for improved treatment planning of prostate cancer

NASA Astrophysics Data System (ADS)

Venugopal, Niranjan

Prostate cancer is the most common malignancy afflicting Canadian men in 2011. Physicians use digital rectal exams (DRE), blood tests for prostate specific antigen (PSA) and transrectal ultrasound (TRUS)-guided biopsies for the initial diagnosis of prostate cancer. None of these tests detail the spatial extent of prostate cancer - information critical for using new therapies that can target cancerous prostate. With an MRI technique called proton magnetic resonance spectroscopic imaging (1H-MRSI), biochemical analysis of the entire prostate can be done without the need for biopsy, providing detailed information beyond the non-specific changes in hardness felt by an experienced urologist in a DRE, the presence of PSA in blood, or the "blind-guidance" of TRUS-guided biopsy. A hindrance to acquiring high quality 1H-MRSI data comes from signal originating from fatty tissue surrounding prostate that tends to mask or distort signal from within the prostate, thus reducing the overall clinical usefulness of 1H-MRSI data. This thesis has three major areas of focus: 1) The development of an optimized 1H-MRSI technique, called conformal voxel magnetic resonance spectroscopy (CV-MRS), to deal the with removal of unwanted lipid contaminating artifacts at short and long echo times. 2) An in vivo human study to test the CV-MRS technique, including healthy volunteers and cancer patients scheduled for radical prostatectomy or radiation therapy. 3) A study to determine the efficacy of using the 1H-MRSI data for optimized radiation treatment planning using modern delivery techniques like intensity modulated radiation treatment. Data collected from the study using the optimized CV-MRS method show significantly reduced lipid contamination resulting in high quality spectra throughout the prostate. Combining the CV-MRS technique with spectral-spatial excitation further reduced lipid contamination and opened up the possibility of detecting metabolites with short T2 relaxation times

Characterization of Desmoglein Expression in the Normal Prostatic Gland. Desmoglein 2 Is an Independent Prognostic Factor for Aggressive Prostate Cancer

PubMed Central

Barber, Alison G.; Castillo-Martin, Mireia; Bonal, Dennis M.; Rybicki, Benjamin A.; Christiano, Angela M.; Cordon-Cardo, Carlos

2014-01-01

Purpose The expression of desmogleins (DSGs), which are known to be crucial for establishing and maintaining the cell-cell adhesion required for tissue integrity, has been well characterized in the epidermis and hair follicle; however, their expression in other epithelial tissues such as prostate is poorly understood. Although downregulation of classical cadherins, such as E-cadherin, has been described in prostate cancer tissue samples, the expression of desmogleins has only been previously reported in prostate cancer cell lines. In this study we characterized desmoglein expression in normal prostate tissues, and further investigated whether Desmoglein 2 (DSG2) expression specifically can serve as a potential clinical prognostic factor for patients diagnosed with primary prostate cancer. Experimental Design We utilized immunofluorescence to examine DSG2 expression in normal prostate (n = 50) and in a clinically well-characterized cohort of prostate cancer patients (n = 414). Correlation of DSG2 expression with clinico-pathological characteristics and biochemical recurrence was analyzed to assess its clinical significance. Results These studies revealed that DSG2 and DSG4 were specifically expressed in prostatic luminal cells, whereas basal cells lack their expression. In contrast, DSG1 and DSG3 were not expressed in normal prostate epithelium. Further analyses of DSG2 expression in prostate cancer revealed that reduced levels of this biomarker were a significant independent marker of poor clinical outcome. Conclusion Here we report for the first time that a low DSG2 expression phenotype is a useful prognostic biomarker of tumor aggressiveness and may serve as an aid in identifying patients with clinically significant prostate cancer. PMID:24896103

Protective effect of zinc on N-methyl-N-nitrosourea and testosterone-induced prostatic intraepithelial neoplasia in the dorsolateral prostate of Sprague Dawley rats.

PubMed

Banudevi, Sivanantham; Elumalai, Perumal; Sharmila, Govindaraj; Arunkumar, Ramachandran; Senthilkumar, Kalimuthu; Arunakaran, Jagadeesan

2011-09-01

Previous studies have suggested that zinc exerts anticarcinogenic and antiproliferative effects against prostate cancer both in vitro and in rat ventral prostate. Zinc accumulation diminishes early in the course of prostate malignancy and it inhibits the growth of several carcinoma cells through induction of cell cycle arrest and apoptosis. In this study, we have investigated the influence of zinc on N-methyl-N-nitrosourea (MNU) and testosterone (T)-induced prostatic intraepithelial neoplasia in the dorsolateral prostate of Sprague Dawley (SD) rats. The results indicate that zinc plays an important role in prostate carcinogenesis. Increased tumor incidence was accompanied by a decrease in prostatic acid phosphatase activity, citrate, zinc, glutathione-S-transferase, reduced glutathione, p53, B-cell lymphoma protein (Bcl-2)-associated X protein and caspase-3 levels in MNU + T-treated rats. On the contrary, significantly increased phase I drug metabolizing enzyme activities, lipid peroxide, hydrogen peroxide, proliferating cell nuclear antigen, Bcl-2 and Bcl-X(L) protein levels were observed in the dorsolateral prostate of MNU + T-treated rats. Simultaneous zinc supplementation significantly reversed these effects in MNU + T-treated rats. Signs of dysplasia, a characteristic of prostatic intraepithelial neoplasia, were evident in the dorsolateral prostatic tissue sections by MNU + T administration. However, zinc supplementation has reversed these effects in the dorsolateral prostatic histoarchitecture. These results suggest that zinc may act as an essential trace element against MNU and testosterone-induced prostatic preneoplastic progression in SD rats.

Prostate specific antigen enhances the innate defence of prostatic epithelium against Escherichia coli infection.

PubMed

Townes, Claire L; Ali, Ased; Gross, Naomi; Pal, Deepali; Williamson, Stuart; Heer, Rakesh; Robson, Craig N; Pickard, Robert S; Hall, Judith

2013-10-01

This study investigated whether the increase in serum prostate specific antigen (PSA) typically seen during male urinary tract infection (UTI) is incidental or reflects an innate defence mechanism of the prostate. The protective roles of the whey-acid-motif-4-disulphide core (WFDC) proteins, secretory leukoproteinase inhibitor (SLPI) and WFDC2, in the prostate were also examined. UTI recurrence was assessed retrospectively in men following initial UTI by patient interview. PSA, SLPI, and WFDC2 gene expression were assessed using biopsy samples. LNCaP and DU145 in vitro prostate cell models were utilized to assess the effects of an Escherichia coli challenge on PSA and WFDC gene expression, and bacterial invasion of the prostate epithelium. The effects of PSA on WFDC antimicrobial properties were studied using recombinant peptides and time-kill assays. Men presenting with PSA >4 ng/ml at initial UTI were less likely to have recurrent (r) UTI than those with PSA <4 ng/ml [2/15 (13%) vs. 7/10 (70%), P < 0.01]. Genes encoding PSA, SLPI and WFDC2, were expressed in prostatic epithelium, and the PSA and SLPI proteins co-localized in vivo. Challenging LNCaP (PSA-positive) cells with E. coli increased PSA, SLPI, and WFDC2 gene expression (P < 0.05), and PSA synthesis (P < 0.05), and reduced bacterial invasion. Pre-incubation of DU145 (PSA-negative) cells with PSA also decreased bacterial invasion. In vitro incubation of recombinant SLPI and WFDC2 with PSA resulted in peptide proteolysis and increased E. coli killing. Increased PSA during UTI appears protective against rUTI and in vitro is linked to proteolysis of WFDC proteins supporting enhanced prostate innate defences. Copyright © 2013 Wiley Periodicals, Inc.

Association between asymptomatic inflammatory prostatitis NIH category IV and prostatic calcification in patients with obstructive benign prostatic hyperplasia.

PubMed

Engelhardt, Paul F; Seklehner, Stephan; Brustmann, Herman; Riedl, Claus R; Lusuardi, Lukas

2016-06-01

The aim of this study was to evaluate the incidence of prostatic calcification and prostatitis NIH category IV in patients with obstructive BPH. Ninety-six patients with obstructive BPH who had undergone transurethral electroresection of the prostate gland were evaluated. In accordance with a preoperative transrectal ultrasound examination, patients were divided into one group with prostatic calcification (N.=31) and one without (N.=65). Prostatitis NIH category IV was classified according to the grading system by Irani. Correlations between the incidence of prostatic calcification, histological prostatitis, PSA, uric acid, cholesterol, triglycerides, CRP, IPSS, IIEF-25, and NIC-CPSI were analyzed. A stone analysis of prostatic calcification was performed using X-ray powder diffraction. Sixty-nine (71.9%) patients had NIH category IV prostatitis, accounting for 83.9% of those with prostatic calcification versus 66.1% of those without (P<0.04). Significant correlations were found between prostatic calcification and the severity of inflammation (P<0.02) as well as the NIH-CPSI subdomain of urinary symptoms (P<0.02). The only predictor for prostatic calcifications were elevated levels of uric acid. Such patients were 1.4times more likely of having calcifications in the prostate gland (OR=1.4, P<0.047). Stone analysis revealed the following: apatite in 41.7%, whewellite in 29.2%, weddellite and brushite in 8.7% each, whitlockite, apatite/whewellite and organic substances in 4.2%. On ultrasound examination, one third of patients who were treated with TURP for obstructive BPH had prostatic calcification. These were significantly more common in patients with NIH category IV prostatitis.

Reduction of prostate intrafraction motion using gas-release rectal balloons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su Zhong; Zhao Tianyu; Li Zuofeng

2012-10-15

Purpose: To analyze prostate intrafraction motion using both non-gas-release (NGR) and gas-release (GR) rectal balloons and to evaluate the ability of GR rectal balloons to reduce prostate intrafraction motion. Methods: Twenty-nine patients with NGR rectal balloons and 29 patients with GR balloons were randomly selected from prostate patients treated with proton therapy at University of Florida Proton Therapy Institute (Jacksonville, FL). Their pretreatment and post-treatment orthogonal radiographs were analyzed, and both pretreatment setup residual error and intrafraction-motion data were obtained. Population histograms of intrafraction motion were plotted for both types of balloons. Population planning target-volume (PTV) margins were calculated withmore » the van Herk formula of 2.5{Sigma}+ 0.7{sigma} to account for setup residual errors and intrafraction motion errors. Results: Pretreatment and post-treatment radiographs indicated that the use of gas-release rectal balloons reduced prostate intrafraction motion along superior-inferior (SI) and anterior-posterior (AP) directions. Similar patient setup residual errors were exhibited for both types of balloons. Gas-release rectal balloons resulted in PTV margin reductions from 3.9 to 2.8 mm in the SI direction, 3.1 to 1.8 mm in the AP direction, and an increase from 1.9 to 2.1 mm in the left-right direction. Conclusions: Prostate intrafraction motion is an important uncertainty source in radiotherapy after image-guided patient setup with online corrections. Compared to non-gas-release rectal balloons, gas-release balloons can reduce prostate intrafraction motion in the SI and AP directions caused by gas buildup.« less

Comparison of prostate cancer gene 3 score, prostate health index and percentage free prostate-specific antigen for differentiating histological inflammation from prostate cancer and other non-neoplastic alterations of the prostate at initial biopsy.

PubMed

De Luca, Stefano; Passera, Roberto; Bollito, Enrico; Manfredi, Matteo; Scarpa, Roberto Mario; Sottile, Antonino; Randone, Donato Franco; Porpiglia, Francesco

2014-12-01

To determine if prostate cancer gene 3 (PCA3) score, Prostate Health Index (PHI), and percent free prostate-specific antigen (%fPSA) may be used to differentiate prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH) and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA and negative digital rectal examination (DRE). in the present prospective study, 274 patients, undergoing PCA3 score, PHI and %fPSA assessments before initial biopsy, were enrolled. Three multivariate logistic regression models were used to test PCA3 score, PHI and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the 'gray zone' of PSA (4-10 ng/ml) cohort (188 individuals). The determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (Odds Ratio [OR]=0.97, 0.96 and 0.94, respectively). Unit increase of PHI was the only risk factor for prostatitis vs. BPH (OR=1.06), and unit increase of PCA3 score for HG-PIN vs. prostatitis (OR=0.98). In the 'gray zone' PSA cohort, the determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (OR=0.96, 0.94 and 0.92, respectively), PCA3 score and PHI for prostatitis vs. BPH (OR=0.96 and 1.08, respectively), and PCA3 score for prostatitis vs. HG-PIN (OR=0.97). The clinical benefit of using PCA3 score and PHI to estimate prostatitis vs. PCa was comparable; even %fPSA had good diagnostic performance, being a faster and cheaper marker. PHI was the only determinant for prostatitis vs. BPH, while PCA3 score for prostatitis vs. HG-PIN. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Clinical and microbiological characteristics of spontaneous acute prostatitis and transrectal prostate biopsy-related acute prostatitis: Is transrectal prostate biopsy-related acute prostatitis a distinct acute prostatitis category?

PubMed

Kim, Jong Wook; Oh, Mi Mi; Bae, Jae Hyun; Kang, Seok Ho; Park, Hong Seok; Moon, Du Geon

2015-06-01

This study aimed to compare the clinical and microbiological characteristics between acute bacterial prostatitis and transrectal biopsy-related acute prostatitis. We retrospectively reviewed the records of 135 patients hospitalized for acute prostatitis in three urological centers between 2004 and 2013. Acute bacterial prostatitis was diagnosed according to typical symptoms, findings of physical examination, and laboratory test results. Clinical variables, laboratory test results, and anti-microbial susceptibility results were reviewed. Patients were classified into the spontaneous acute prostatitis group (S-ABP) or biopsy-related acute prostatitis (Bx-ABP) for comparison of their clinical, laboratory, and microbiological findings. The mean age of all patients was 61.7 ± 12.9 years. Compared with S-ABP patients, Bx-ABP patients were significantly older, had larger prostate volumes, higher PSA values, higher peak fever temperatures, and higher incidence of septicemia and antibiotic-resistant bacteria. Overall, of the 135 patients, 57.8% had positive bacterial urine and/or blood cultures. Bx-ABP patients had a higher incidence of bacterial (urine and/or blood) positive cultures compared to S-ABP patients (66.7% versus 55.6%). Escherichia coli was the predominant organism in both groups, but it was more common in Bx-ABP (88.9%) than in S-ABP (66.7%). Extended spectrum beta-lactamase -producing bacteria accounted for 64.7% of culture-positive patients in the Bx-ABP group compared to 13.3% in the S-ABP group. Bx-ABP patients showed a higher incidence of septicemia and antibiotic-resistant bacteria than S-ABP patients. These results have important implications for the management and antimicrobial treatment of Bx-ABP, which may well deserve to be considered a distinct prostatitis category. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

ONC201 Targets AR and AR-V7 Signaling, Reduces PSA, and Synergizes with Everolimus in Prostate Cancer.

PubMed

Lev, Avital; Lulla, Amriti R; Ross, Brian C; Ralff, Marie D; Makhov, Petr B; Dicker, David T; El-Deiry, Wafik S

2018-05-01

Androgen receptor (AR) signaling plays a key role in prostate cancer progression, and androgen deprivation therapy (ADT) is a mainstay clinical treatment regimen for patients with advanced disease. Unfortunately, most prostate cancers eventually become androgen-independent and resistant to ADT with patients progressing to metastatic castration-resistant prostate cancer (mCRPC). Constitutively activated AR variants (AR-V) have emerged as mediators of resistance to AR-targeted therapy and the progression of mCRPC, and they represent an important therapeutic target. Out of at least 15 AR-Vs described thus far, AR-V7 is the most abundant, and its expression correlates with ADT resistance. ONC201/TIC10 is the founding member of the imipridone class of small molecules and has shown anticancer activity in a broad range of tumor types. ONC201 is currently being tested in phase I/II clinical trials for advanced solid tumors, including mCRPC, and hematologic malignancies. There has been promising activity observed in patients in early clinical testing. This study demonstrates preclinical single-agent efficacy of ONC201 using in vitro and in vivo models of prostate cancer. ONC201 has potent antiproliferative and proapoptotic effects in both castration-resistant and -sensitive prostate cancer cells. Furthermore, the data demonstrate that ONC201 downregulates the expression of key drivers of prostate cancer such as AR-V7 and downstream target genes including the clinically used biomarker PSA (KLK3). Finally, the data also provide a preclinical rationale for combination of ONC201 with approved therapeutics for prostate cancer such as enzalutamide, everolimus (mTOR inhibitor), or docetaxel. Implications: The preclinical efficacy of ONC201 as a single agent or in combination, in hormone-sensitive or castration-resistant prostate cancer, suggests the potential for immediate clinical translation. Mol Cancer Res; 16(5); 754-66. ©2018 AACR . ©2018 American Association for Cancer

Inhibitor of p52 NF-κB subunit and androgen receptor (AR) interaction reduces growth of human prostate cancer cells by abrogating nuclear translocation of p52 and phosphorylated ARser81

PubMed Central

Mehraein-Ghomi, Farideh; Church, Dawn R.; Schreiber, Cynthia L.; Weichmann, Ashley M.; Basu, Hirak S.; Wilding, George

2015-01-01

Accumulating evidence shows that androgen receptor (AR) activation and signaling plays a key role in growth and progression in all stages of prostate cancer, even under low androgen levels or in the absence of androgen in the castration-resistant prostate cancer. Sustained activation of AR under androgen-deprived conditions may be due to its interaction with co-activators, such as p52 NF-κB subunit, and/or an increase in its stability by phosphorylation that delays its degradation. Here we identified a specific inhibitor of AR/p52 interaction, AR/p52-02, via a high throughput screen based on the reconstitution of Gaussia Luciferase. We found that AR/p52-02 markedly inhibited growth of both castration-resistant C4-2 (IC50 ∼6 μM) and parental androgen-dependent LNCaP (IC50 ∼4 μM) human prostate cancer cells under low androgen conditions. Growth inhibition was associated with significantly reduced nuclear p52 levels and DNA binding activity, as well as decreased phosphorylation of AR at serine 81, increased AR ubiquitination, and decreased AR transcriptional activity as indicated by decreased prostate-specific antigen (PSA) mRNA levels in both cell lines. AR/p52-02 also caused a reduction in levels of p21WAF/CIP1, which is a direct AR targeted gene in that its expression correlates with androgen stimulation and mitogenic proliferation in prostate cancer under physiologic levels of androgen, likely by disrupting the AR signaling axis. The reduced level of cyclinD1 reported previously for this compound may be due to the reduction in nuclear presence and activity of p52, which directly regulates cyclinD1 expression, as well as the reduction in p21WAF/CIP1, since p21WAF/CIP1 is reported to stabilize nuclear cyclinD1 in prostate cancer. Overall, the data suggest that specifically inhibiting the interaction of AR with p52 and blocking activity of p52 and pARser81 may be an effective means of reducing castration-resistant prostate cancer cell growth. PMID:26622945

Inhibition of Carbonic Anhydrase IX by Ureidosulfonamide Inhibitor U104 Reduces Prostate Cancer Cell Growth, But Does Not Modulate Daunorubicin or Cisplatin Cytotoxicity.

PubMed

Riemann, Anne; Güttler, Antje; Haupt, Verena; Wichmann, Henri; Reime, Sarah; Bache, Matthias; Vordermark, Dirk; Thews, Oliver

2018-03-05

Carbonic anhydrase (CA) IX has emerged as a promising target for cancer therapy. It is highly upregulated in hypoxic regions and mediates pH regulation critical for tumor cell survival as well as extracellular acidification of the tumor microenvironment, which promotes tumor aggressiveness via various mechanisms, such as augmenting metastatic potential. Therefore, the aim of this study was to analyze the complex interdependency between CA IX and the tumor microenvironment in prostate tumor cells with regard to potential therapeutic implications. CA IX was upregulated by hypoxia as well as acidosis in prostate cancer cells. This induction did not modulate intracellular pH but led to extracellular acidification. Pharmacological inhibition of CA IX activity by U104 (SLC-0111) resulted in a reduction in tumor cell growth and an increase in apoptotic cell death. Intracellular pH was reduced under normoxic and even more so under hypoxic conditions when CA IX level was high. However, although intracellular pH regulation was disturbed, targeting CA IX in combination with daunorubicin or cisplatin did not intensify apoptotic tumor cell death. Hence, targeting CA IX in prostate cancer cells can lead to intracellular pH dysregulation and, consequently, can reduce cellular growth and elevate apoptotic cell death. Attenuation of extracellular acidification by blocking CA IX might additionally impede tumor progression and metastasis. However, no beneficial effect was seen when targeting CA IX in combination with chemotherapeutic drugs.

Recent advances in prostate development and links to prostatic diseases

PubMed Central

Powers, Ginny L.

2013-01-01

The prostate is a branched ductal-acinar gland that is part of the male reproductive tract. Prostate development depends upon the integration of steroid hormone signals, paracrine interactions between the stromal and epithelial tissue layers, and the actions of cell autonomous factors. Several genes and signalling pathways are known to be required for one or more steps of prostate development including epithelial budding, duct elongation, branching morphogenesis, and/or cellular differentiation. Recent progress in the field of prostate development has included the application of genome-wide technologies including serial analysis of gene expression (SAGE), expression profiling microarrays, and other large scale approaches to identify new genes and pathways that are essential for prostate development. The aggregation of experimental results into online databases by organized multi-lab projects including the Genitourinary Developmental Molecular Atlas Project (GUDMAP) has also accelerated the understanding of molecular pathways that function during prostate development and identified links between prostate anatomy and molecular signaling. Rapid progress has also recently been made in understanding the nature and role of candidate stem cells in the developing and adult prostate. This has included the identification of putative prostate stem cell markers, lineage tracing, and organ reconstitution studies. However, several issues regarding their origin, precise nature, and possible role(s) in disease remain unresolved. Nevertheless, several links between prostatic developmental mechanisms and the pathogenesis of prostatic diseases including benign prostatic hyperplasia and prostate cancer have led to recent progress on targeting developmental pathways as therapeutic strategies for these diseases. PMID:23335485

A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

PubMed Central

Archibald, Monica; Pritchard, Tara; Nehoff, Hayley; Rosengren, Rhonda J; Greish, Khaled; Taurin, Sebastien

2016-01-01

Castrate-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. Several tyrosine kinases have been implicated in the development and growth of CRPC, as such targeting these kinases may offer an alternative therapeutic strategy. We established the combination of two tyrosine kinase inhibitors (TKIs), sorafenib and nilotinib, as the most cytotoxic. In addtion, to improve their bioavailability and reduce their metabolism, we encapsulated sorafenib and nilotinib into styrene-co-maleic acid micelles. The micelles’ charge, size, and release rate were characterized. We assessed the effect of the combination on the cytotoxicity, cell cycle, apoptosis, protein expression, tumor spheroid integrity, migration, and invasion. The micelles exhibited a mean diameter of 100 nm, a neutral charge, and appeared highly stable. The micellar TKIs promoted greater cytotoxicity, decreased cell proliferation, and increased apoptosis relative to the free TKIs. In addition, the combination reduced the expression and activity of several tyrosine kinases and reduced tumor spheroid integrity and metastatic potential of CRPC cell lines more efficiently than the single treatments. The combination increased the therapeutic potential and demonstrated the relevance of a targeted combination therapy for the treatment of CRPC. In addition, the efficacy of the encapsulated drugs provides the basis for an in vivo preclinical testing. PMID:26811677

SU-E-J-150: Impact of Intrafractional Prostate Motion On the Accuracy and Efficiency of Prostate SBRT Delivery: A Retrospective Analysis of Prostate Tracking Log Files

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiang, H; Hirsch, A; Willins, J

2014-06-01

Purpose: To measure intrafractional prostate motion by time-based stereotactic x-ray imaging and investigate the impact on the accuracy and efficiency of prostate SBRT delivery. Methods: Prostate tracking log files with 1,892 x-ray image registrations from 18 SBRT fractions for 6 patients were retrospectively analyzed. Patient setup and beam delivery sessions were reviewed to identify extended periods of large prostate motion that caused delays in setup or interruptions in beam delivery. The 6D prostate motions were compared to the clinically used PTV margin of 3–5 mm (3 mm posterior, 5 mm all other directions), a hypothetical PTV margin of 2–3 mmmore » (2 mm posterior, 3 mm all other directions), and the rotation correction limits (roll ±2°, pitch ±5° and yaw ±3°) of CyberKnife to quantify beam delivery accuracy. Results: Significant incidents of treatment start delay and beam delivery interruption were observed, mostly related to large pitch rotations of ≥±5°. Optimal setup time of 5–15 minutes was recorded in 61% of the fractions, and optimal beam delivery time of 30–40 minutes in 67% of the fractions. At a default imaging interval of 15 seconds, the percentage of prostate motion beyond PTV margin of 3–5 mm varied among patients, with a mean at 12.8% (range 0.0%–31.1%); and the percentage beyond PTV margin of 2–3 mm was at a mean of 36.0% (range 3.3%–83.1%). These timely detected offsets were all corrected real-time by the robotic manipulator or by operator intervention at the time of treatment interruptions. Conclusion: The durations of patient setup and beam delivery were directly affected by the occurrence of large prostate motion. Frequent imaging of down to 15 second interval is necessary for certain patients. Techniques for reducing prostate motion, such as using endorectal balloon, can be considered to assure consistently higher accuracy and efficiency of prostate SBRT delivery.« less

Relationship between prostate-specific antigen and obesity in prostate cancer screening: analysis of a large cohort in Japan.

PubMed

Kubota, Yasuaki; Seike, Kensaku; Maeda, Shinichi; Shinohara, Yuka; Iwata, Masamitsu; Sugimoto, Norio

2011-01-01

Previous studies have shown that lower prostate-specific antigen (PSA) levels in obese men might decrease the sensitivity of prostate cancer screening, leading to delayed diagnosis and unfavorable prognosis. We examined whether the effect of obesity is important in prostate cancer screening of Japanese men, who have a low prevalence of obesity. We analyzed 19,294 male subjects from a large cohort of Toyota Motor Corporation (TMC) employees (aged > 50 years, serum PSA level ≤ 4.0 ng/mL) who underwent physical examinations from August 2006 to December 2009. The relationship between PSA level and obesity-related factors was analyzed by simple and multiple regression analysis. The relationships between six body mass index (BMI) categories, and PSA level and PSA mass (PSA concentration × plasma volume) were analyzed. PSA level decreased significantly with increasing BMI, but the coefficient of determination was very low. Mean PSA values decreased from 1.02 to 0.85 ng/mL as BMI increased from underweight (BMI <18.5) to morbidly obese (BMI >35). However, PSA mass peaked in the overweight category and was slightly reduced with increasing BMI. On multiple regression analysis, PSA level was influenced by age, diastolic blood pressure and high-density lipoprotein as well as BMI. We found an inverse but weak relationship between PSA level and BMI. Obesity seems to have very limited influence on prostate cancer screening in this population. Nonetheless, when considering indications for prostatic biopsy in obese men, we should be aware that the hemodilution effect might reduce PSA levels. © 2010 The Japanese Urological Association.

Pharmacodynamic and pharmacokinetic studies and prostatic tissue distribution of fosfomycin tromethamine in bacterial prostatitis or normal rats.

PubMed

Fan, L; Shang, X; Zhu, J; Ma, B; Zhang, Q

2018-05-02

In this study, we assessed the therapeutic effects of fosfomycin tromethamine (FT) in a bacterial prostatitis (BP) rat model. The BP model was induced by Escherichia coli and was demonstrated after 7 days microbiologically and histologically. Then, 25 BP rats selected were randomly divided into five treatment groups: model group, positive group, FT-3 day group, FT-7 day group and FT-14 day group. Ventral lobes of prostate from all animals were removed, and the serum samples were collected at the end of the experiments. Microbiological cultures and histological findings of the prostate samples demonstrated reduced bacterial growth and improved inflammatory responses in FT-treatment groups compared with the model group, indicating that FT against prostatic infection induced by E. coli showed good antibacterial effects. Moreover, plasma pharmacokinetics and prostatic distribution of fosfomycin were studied and compared in BP and normal rats. The concentrations of fosfomycin in samples were analysed by liquid chromatography-tandem mass spectrometry. There were no differences in plasma pharmacokinetic parameters between two groups. But significantly higher penetration of fosfomycin into prostatic tissues was found in BP rats. We therefore suggested that FT had a good therapeutic effect on BP and it might be used in curing masculine reproductive system diseases. © 2018 Blackwell Verlag GmbH.

Abiraterone acetate in the treatment of prostate cancer.

PubMed

Thakur, Abhimanyu; Roy, Aishwarya; Ghosh, Arijit; Chhabra, Mohit; Banerjee, Sugato

2018-05-01

Among all cancer-related death, prostate cancer accounts for the second prominent reason for cancer-associated death in men. Despite the castration mediated reduction in testosterone synthesis, adrenal glands, as well as tissues of prostate cancer, continue to produce androgens, which ultimately lead to the growth of prostate cancer. This phase is referred as metastatic castration-resistant prostate cancer, which throws an obstacle to treatment. Androgen antagonists, in addition to deprivation of hormone, is being used for reducing the level of prostate-specific antigen but has not successfully come in front as a choice for prolonging the life of patients suffering from prostate cancer. In this prevailing scenario, abiraterone acetate (AA) has proved to be a boon for patients suffering from prostate cancer. AA selectively inhibits the actions of enzymes C17, 20-lyase and 17α-hydroxylase on cytochrome P450 (CYP) 17 when administered orally. The signaling of androgen receptor, being important for primary to metastatic phases of prostate cancer, CYP17 is essential for the synthesis of androgen. Herein, the in-detail pharmacological profile of AA, including androgen signaling, mechanism of action of AA, mechanism of AA resistance, pharmacokinetics, latest clinical findings, predictive markers, optimal treatment sequence, toxicity, and food interaction profiles have been reviewed. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Diagnostic accuracy of urinary prostate protein glycosylation profiling in prostatitis diagnosis.

PubMed

Vermassen, Tijl; Van Praet, Charles; Poelaert, Filip; Lumen, Nicolaas; Decaestecker, Karel; Hoebeke, Piet; Van Belle, Simon; Rottey, Sylvie; Delanghe, Joris

2015-01-01

Although prostatitis is a common male urinary tract infection, clinical diagnosis of prostatitis is difficult. The developmental mechanism of prostatitis is not yet unraveled which led to the elaboration of various biomarkers. As changes in asparagine-linked-(N-)-glycosylation were observed between healthy volunteers (HV), patients with benign prostate hyperplasia and prostate cancer patients, a difference could exist in biochemical parameters and urinary N-glycosylation between HV and prostatitis patients. We therefore investigated if prostatic protein glycosylation could improve the diagnosis of prostatitis. Differences in serum and urine biochemical markers and in total urine N-glycosylation profile of prostatic proteins were determined between HV (N=66) and prostatitis patients (N=36). Additionally, diagnostic accuracy of significant biochemical markers and changes in N-glycosylation was assessed. Urinary white blood cell (WBC) count enabled discrimination of HV from prostatitis patients (P<0.001). Urinary bacteria count allowed for discriminating prostatitis patients from HV (P<0.001). Total amount of biantennary structures (urinary 2A/MA marker) was significantly lower in prostatitis patients compared to HV (P<0.001). Combining the urinary 2A/MA marker and urinary WBC count resulted in an AUC of 0.79, 95% confidence interval (CI)=(0.70-0.89) which was significantly better than urinary WBC count (AUC=0.70, 95% CI=[0.59-0.82], P=0.042) as isolated test. We have demonstrated the diagnostic value of urinary N-glycosylation profiling, which shows great potential as biomarker for prostatitis. Further research is required to unravel the developmental course of prostatic inflammation.

Does Core Length Taken per cc of Prostate Volume in Prostate Biopsy Affect the Diagnosis of Prostate Cancer?

PubMed

Deliktas, Hasan; Sahin, Hayrettin; Cetinkaya, Mehmet; Dere, Yelda; Erdogan, Omer; Baldemir, Ercan

2016-08-01

The aim of this study was to determine the minimal core length to be taken per cc of prostate volume for an effective prostate biopsy. A retrospective analysis was performed on the records of 379 patients who underwent a first prostate biopsy with 12 to 16 cores under transrectal ultrasound guidance between September 2012 and April 2015. For each patient, the core length per cc of the prostate and the percentage of sampled prostate volume were calculated, and these values were compared between the patients with and without prostate cancer. A total of 348 patients were included in the study. Cancer was determined in 26.4% of patients. The mean core length taken per cc of prostate and the percentage of sampled prostate volume were determined to be 3.40 ± 0.15 mm/cc (0.26%; range, 0.08-0.63 cc) in patients with cancer and 2.75 ± 0.08 mm/cc (0.20%; range, 0.04-0.66 cc) in patients without cancer (P = .000 and P = .000), respectively. Core length taken per cc of prostate of > 3.31 mm/cc was found to be related to an increase in the rates of prostate cancer diagnosis (odds ratio, 2.84; 95% confidence interval, 1.68-4.78). The rate of cancer determination for core length taken per cc of prostate of < 3.31 mm/cc was 19.9% and of > 3.31 mm/cc, 41.1%. Core length taken per cc of prostate and the percentage of sampled prostate volume are important morphometric parameters in the determination of prostate cancer. The results of study suggest a core length per cc of the prostate of > 3.31 mm/cc as a cutoff value for quality assurance. Copyright © 2016 Elsevier Inc. All rights reserved.

Radical Prostatectomy versus Observation for Localized Prostate Cancer

PubMed Central

Wilt, Timothy J.; Brawer, Michael K.; Jones, Karen M.; Barry, Michael J.; Aronson, William J.; Fox, Steven; Gingrich, Jeffrey R.; Wei, John T.; Gilhooly, Patricia; Grob, B. Mayer; Nsouli, Imad; Iyer, Padmini; Cartagena, Ruben; Snider, Glenn; Roehrborn, Claus; Sharifi, Roohollah; Blank, William; Pandya, Parikshit; Andriole, Gerald L.; Culkin, Daniel; Wheeler, Thomas

2012-01-01

BACKGROUND The effectiveness of surgery versus observation for men with localized prostate cancer detected by means of prostate-specific antigen (PSA) testing is not known. METHODS From November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer (mean age, 67 years; median PSA value, 7.8 ng per milliliter) to radical prostatectomy or observation and followed them through January 2010. The primary outcome was all-cause mortality; the secondary outcome was prostate-cancer mortality. RESULTS During the median follow-up of 10.0 years, 171 of 364 men (47.0%) assigned to radical prostatectomy died, as compared with 183 of 367 (49.9%) assigned to observation (hazard ratio, 0.88; 95% confidence interval [CI], 0.71 to 1.08; P = 0.22; absolute risk reduction, 2.9 percentage points). Among men assigned to radical prostatectomy, 21 (5.8%) died from prostate cancer or treatment, as compared with 31 men (8.4%) assigned to observation (hazard ratio, 0.63; 95% CI, 0.36 to 1.09; P = 0.09; absolute risk reduction, 2.6 percentage points). The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age, race, coexisting conditions, self-reported performance status, or histologic features of the tumor. Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter (P = 0.04 for interaction) and possibly among those with intermediate-risk or high-risk tumors (P = 0.07 for interaction). Adverse events within 30 days after surgery occurred in 21.4% of men, including one death. CONCLUSIONS Among men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up. Absolute differences were less than 3 percentage points. (Funded by the Department of Veterans Affairs Cooperative Studies

Psychosocial and Cultural Barriers to Prostate Cancer Screening: Racial Comparisons

DTIC Science & Technology

2009-03-01

37 REPORTABLE OUTCOMES ............................................................................................... 38 KEY RESEARCH...difference in outcome for prostate cancer, then a fatalistic attitude can develop and discourage screening behavior. Belief in one’s ability to...cancer screening among African American men and reduce racial disparities in prostate cancer outcomes . Specifically, the proposed project examines

Prostate brachytherapy

MedlinePlus

Implant therapy - prostate cancer; Radioactive seed placement; Internal radiation therapy - prostate; High dose radiation (HDR) ... CT scan to plan and then place the seeds that deliver radiation into your prostate. The seeds ...

Effect of Black maca (Lepidium meyenii) on one spermatogenic cycle in rats.

PubMed

Gonzales, G F; Nieto, J; Rubio, J; Gasco, M

2006-10-01

Lepidium meyenii (Maca) grows exclusively between 4000 and 4500 m above sea level in the Peruvian central Andes. The hypocotyls of this plant are traditionally used in the Andean region for their supposed fertility-enhancing properties. The hypocotyls have different colours. Of these, Black maca has better effects on spermatogenesis. The present study aimed to test the hypothesis that Black maca has early effects during a spermatogenic cycle (12 days) of male rats. For this, testicular spermatid, epididymal sperm and vas deferens sperm counts were measured after 1, 3, 5, 7 and 12 days of treatment with Black maca. Aqueous extract of Black maca was given orally by daily gavage at a dose of 2 g kg(-1). In a spermatogenic cycle, compared with day 1, daily sperm production (DSP) was lower at day 7 (control), whereas with Black maca, the difference was observed at day 12. Epididymal sperm count was higher in rats treated with Black maca at days 1, 3 and 7, but similar to controls at days 5 and 12; similarly sperm counts in vas deferens was higher in rats treated with Black maca in days 3, 5 and 7, but similar to controls at days 1 and 12. From this, it is suggested that first action of Black maca was at epididymal level increasing sperm count after 1 day of treatment, whereas an increase in sperm count was observed in vas deferens at day 3 of treatment. Finally, an increase in DSP was observed after 7 days of treatment with Black maca. Testicular testosterone was not affected after 7 days treatment with Black maca. In conclusion, Black maca affects sperm count as early as 1 day after beginning of treatment.

Plant Flavone Apigenin Binds to Nucleic Acid Bases and Reduces Oxidative DNA Damage in Prostate Epithelial Cells

PubMed Central

Bhaskaran, Natarajan; Gupta, Sanjay

2014-01-01

Oxidative stress has been linked to prostate carcinogenesis as human prostate tissue is vulnerable to oxidative DNA damage. Apigenin, a dietary plant flavone, possesses anti-proliferative and anticancer effects; however, its antioxidant properties have not been fully elucidated. We investigated sub-cellular distribution of apigenin, it’s binding to DNA and protective effects against H2O2-induced DNA damage using transformed human prostate epithelial RWPE-1 cells and prostate cancer LNCaP, PC-3 and DU145 cells. Exposure of cells to apigenin exhibited higher accumulation in RWPE-1 and LNCaP cells, compared to PC-3 and DU145 cells. The kinetics of apigenin uptake in LNCaP cells was estimated with a Km value of 5 µmole/L and Vmax of 190 pmoles/million cells/h. Sub-cellular fractionation demonstrated that nuclear matrix retains the highest concentration of apigenin (45.3%), followed by cytosol (23.9%), nuclear membranes (17.9%) and microsomes (12.9%), respectively. Spectroscopic analysis of apigenin with calf-thymus DNA exhibited intercalation as the dominant binding mode to DNA duplex. Apigenin exposure resulted in significant genoprotective effects in H2O2-stressed RWPE-1 cells by reduction in reactive oxygen species levels. In addition, apigenin exposure suppressed the formation of 8-hydroxy-2′ deoxyguanosine and protected exposed cells from apoptosis. Our studies demonstrate that apigenin is readily taken up by normal prostatic epithelial cells and prostate cancer cells, and is incorporated into their nuclei, where its intercalation with nucleic acid bases may account for its antioxidant and chemopreventive activities. PMID:24614817

Plant flavone apigenin binds to nucleic acid bases and reduces oxidative DNA damage in prostate epithelial cells.

PubMed

Sharma, Haripaul; Kanwal, Rajnee; Bhaskaran, Natarajan; Gupta, Sanjay

2014-01-01

Oxidative stress has been linked to prostate carcinogenesis as human prostate tissue is vulnerable to oxidative DNA damage. Apigenin, a dietary plant flavone, possesses anti-proliferative and anticancer effects; however, its antioxidant properties have not been fully elucidated. We investigated sub-cellular distribution of apigenin, it's binding to DNA and protective effects against H2O2-induced DNA damage using transformed human prostate epithelial RWPE-1 cells and prostate cancer LNCaP, PC-3 and DU145 cells. Exposure of cells to apigenin exhibited higher accumulation in RWPE-1 and LNCaP cells, compared to PC-3 and DU145 cells. The kinetics of apigenin uptake in LNCaP cells was estimated with a Km value of 5 µmole/L and Vmax of 190 pmoles/million cells/h. Sub-cellular fractionation demonstrated that nuclear matrix retains the highest concentration of apigenin (45.3%), followed by cytosol (23.9%), nuclear membranes (17.9%) and microsomes (12.9%), respectively. Spectroscopic analysis of apigenin with calf-thymus DNA exhibited intercalation as the dominant binding mode to DNA duplex. Apigenin exposure resulted in significant genoprotective effects in H2O2-stressed RWPE-1 cells by reduction in reactive oxygen species levels. In addition, apigenin exposure suppressed the formation of 8-hydroxy-2' deoxyguanosine and protected exposed cells from apoptosis. Our studies demonstrate that apigenin is readily taken up by normal prostatic epithelial cells and prostate cancer cells, and is incorporated into their nuclei, where its intercalation with nucleic acid bases may account for its antioxidant and chemopreventive activities.

Transurethral illumination probe design for deep photoacoustic imaging of prostate

NASA Astrophysics Data System (ADS)

Ai, Min; Salcudean, Tim; Rohling, Robert; Abolmaesumi, Purang; Tang, Shuo

2018-02-01

Photoacoustic (PA) imaging with internal light illumination through optical fiber could enable imaging of internal organs at deep penetration. We have developed a transurethral probe with a multimode fiber inserted in a rigid cystoscope sheath for illuminating the prostate. At the distal end, the fiber tip is processed to diffuse light circumferentially over 2 cm length. A parabolic cylinder mirror then reflects the light to form a rectangular-shaped parallel beam which has at least 1 cm2 at the probe surface. The relatively large rectangular beam size can reduce the laser fluence rate on the urethral wall and thus reduce the potential of tissue damage. A 3 cm optical penetration in chicken tissue is achieved at a fluence rate around 7 mJ/cm2 . For further validation, a prostate phantom was built with similar optical properties of the human prostate. A 1.5 cm penetration depth is achieved in the prostate mimicking phantom at 10 mJ/cm2 fluence rate. PA imaging of prostate can potentially be carried out in the future by combining a transrectal ultrasound transducer and the transurethral illumination.

Prostate cancer screening

MedlinePlus

Prostate cancer screening - PSA; Prostate cancer screening - digital rectal exam; Prostate cancer screening - DRE ... level of PSA could mean you have prostate cancer. But other conditions can also cause a high ...

The new Epstein gleason score classification significantly reduces upgrading in prostate cancer patients.

PubMed

De Nunzio, Cosimo; Pastore, Antonio Luigi; Lombardo, Riccardo; Simone, Giuseppe; Leonardo, Costantino; Mastroianni, Riccardo; Collura, Devis; Muto, Giovanni; Gallucci, Michele; Carbone, Antonio; Fuschi, Andrea; Dutto, Lorenzo; Witt, Joern Heinrich; De Dominicis, Carlo; Tubaro, Andrea

2018-06-01

To evaluate the differences between the old and the new Gleason score classification systems in upgrading and downgrading rates. Between 2012 and 2015, we identified 9703 patients treated with retropubic radical prostatectomy (RP) in four tertiary centers. Biopsy specimens as well as radical prostatectomy specimens were graded according to both 2005 Gleason and 2014 ISUP five-tier Gleason grading system (five-tier GG system). Upgrading and downgrading rates on radical prostatectomy were first recorded for both classifications and then compared. The accuracy of the biopsy for each histological classification was determined by using the kappa coefficient of agreement and by assessing sensitivity, specificity, positive and negative predictive value. The five-tier GG system presented a lower clinically significant upgrading rate (1895/9703: 19,5% vs 2332/9703:24.0%; p = .001) and a similar clinically significant downgrading rate (756/9703: 7,7% vs 779/9703: 8%; p = .267) when compared to the 2005 ISUP classification. When evaluating their accuracy, the new five-tier GG system presented a better specificity (91% vs 83%) and a better negative predictive value (78% vs 60%). The kappa-statistics measures of agreement between needle biopsy and radical prostatectomy specimens were poor and good respectively for the five-tier GG system and for the 2005 Gleason score (k = 0.360 ± 0.007 vs k = 0.426 ± 0.007). The new Epstein classification significantly reduces upgrading events. The implementation of this new classification could better define prostate cancer aggressiveness with important clinical implications, particularly in prostate cancer management. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Fiducial marker guided prostate radiotherapy: a review

PubMed Central

Jain, Suneil; Hounsell, Alan R; O'Sullivan, Joe M

2016-01-01

Image-guided radiotherapy (IGRT) is an essential tool in the accurate delivery of modern radiotherapy techniques. Prostate radiotherapy positioned using skin marks or bony anatomy may be adequate for delivering a relatively homogeneous whole-pelvic radiotherapy dose, but these surrogates are not reliable when using reduced margins, dose escalation or hypofractionated stereotactic radiotherapy. Fiducial markers (FMs) for prostate IGRT have been in use since the 1990s. They require surgical implantation and provide a surrogate for the position of the prostate gland. A variety of FMs are available and they can be used in a number of ways. This review aimed to establish the evidence for using prostate FMs in terms of feasibility, implantation procedures, types of FMs used, FM migration, imaging modalities used and the clinical impact of FMs. A search strategy was defined and a literature search was carried out in Medline. Inclusion and exclusion criteria were applied, which resulted in 50 articles being included in this review. The evidence demonstrates that FMs provide a more accurate surrogate for the position of the prostate than either external skin marks or bony anatomy. A combination of FM alignment and soft-tissue analysis is currently the most effective and widely available approach to ensuring accuracy in prostate IGRT. FM implantation is safe and well tolerated. FM migration is possible but minimal. Standardization of all techniques and procedures in relation to the use of prostate FMs is required. Finally, a clinical trial investigating a non-surgical alternative to prostate FMs is introduced. PMID:27585736

Clinical and Biochemical Influence of Prostatic Stones.

PubMed

Soric, Tomislav; Selimovic, Mirnes; Bakovic, Lada; Šimurina, Tatjana; Selthofer, Robert; Dumic, Jerka

2017-01-01

The study aimed to explore clinical influence of prostatic stones on lower urinary tract symptoms (LUTS), seminal plasma cytokines, and serum biomarkers. A total of 70 men aged ≤50 years with LUTS divided into 2 groups: group with stones (GSt) and group without prostatic stones (GNoSt). All subjects completed the International Prostate Symptom Score (IPSS) questionnaire and National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scoring questionnaire. Pre- and post-prostate massage test and uroflowmetry were performed. The serum concentration of total prostate specific antigen (PSA), free PSA, and free/total PSA (f/t PSA) ratio, seminal concentration of cytokines interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70, and tumor necrosis factor-alpha were measured. GSt subjects had significantly more severe symptoms based on IPSS answers (p = 0.0289). All domains in NIH-CPSI scores were significantly higher in the GSt group: pain (p = 0.001), urinary symptoms (p = 0.023), quality of life (p = 0.008), and with overall (p = 0.003). GSt subjects also had significantly lower maximum urinary flow (Qmax; p = 0.011), lower f/t PSA ratio (p = 0.048), and higher concentration of IL-1β (p = 0.011) and IL-8 (p = 0.001). Prostatic stones may influence the severity of LUTS and the symptoms of chronic prostatitis. They might reduce Qmax rate and lead to reduction of the f/t PSA ratio and produce more severe inflammation causing increased seminal concentration of IL-1β and IL-8. © 2017 S. Karger AG, Basel.

Prostate-Specific Natural Health Products (Dietary Supplements) Radiosensitize Normal Prostate Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hasan, Yasmin; Schoenherr, Diane; Martinez, Alvaro A.

Purpose: Prostate-specific health products (dietary supplements) are taken by cancer patients to alleviate the symptoms linked with poor prostate health. However, the effect of these agents on evidence-based radiotherapy practice is poorly understood. The present study aimed to determine whether dietary supplements radiosensitized normal prostate or prostate cancer cell lines. Methods and Materials: Three well-known prostate-specific dietary supplements were purchased from commercial sources available to patients (Trinovin, Provelex, and Prostate Rx). The cells used in the study included normal prostate lines (RWPE-1 and PWR-1E), prostate tumor lines (PC3, DU145, and LNCaP), and a normal nonprostate line (HaCaT). Supplement toxicity wasmore » assessed using cell proliferation assays [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and cellular radiosensitivity using conventional clonogenic assays (0.5-4Gy). Cell cycle kinetics were assessed using the bromodeoxyuridine/propidium iodide pulse-labeling technique, apoptosis by scoring caspase-3 activation, and DNA repair by assessing gammaH2AX. Results: The cell growth and radiosensitivity of the malignant PC3, DU145, and LNcaP cells were not affected by any of the dietary prostate supplements (Provelex [2mug/mL], Trinovin [10mug/mL], and Prostate Rx [50 mug/mL]). However, both Trinovin (10mug/mL) and Prostate Rx (6mug/mL) inhibited the growth rate of the normal prostate cell lines. Prostate Rx increased cellular radiosensitivity of RWPE-1 cells through the inhibition of DNA repair. Conclusion: The use of prostate-specific dietary supplements should be discouraged during radiotherapy owing to the preferential radiosensitization of normal prostate cells.« less

Diagnostic accuracy of urinary prostate protein glycosylation profiling in prostatitis diagnosis

PubMed Central

Vermassen, Tijl; Van Praet, Charles; Poelaert, Filip; Lumen, Nicolaas; Decaestecker, Karel; Hoebeke, Piet; Van Belle, Simon; Rottey, Sylvie

2015-01-01

Introduction Although prostatitis is a common male urinary tract infection, clinical diagnosis of prostatitis is difficult. The developmental mechanism of prostatitis is not yet unraveled which led to the elaboration of various biomarkers. As changes in asparagine-linked-(N-)-glycosylation were observed between healthy volunteers (HV), patients with benign prostate hyperplasia and prostate cancer patients, a difference could exist in biochemical parameters and urinary N-glycosylation between HV and prostatitis patients. We therefore investigated if prostatic protein glycosylation could improve the diagnosis of prostatitis. Materials and methods Differences in serum and urine biochemical markers and in total urine N-glycosylation profile of prostatic proteins were determined between HV (N = 66) and prostatitis patients (N = 36). Additionally, diagnostic accuracy of significant biochemical markers and changes in N-glycosylation was assessed. Results Urinary white blood cell (WBC) count enabled discrimination of HV from prostatitis patients (P < 0.001). Urinary bacteria count allowed for discriminating prostatitis patients from HV (P < 0.001). Total amount of biantennary structures (urinary 2A/MA marker) was significantly lower in prostatitis patients compared to HV (P < 0.001). Combining the urinary 2A/MA marker and urinary WBC count resulted in an AUC of 0.79, 95% confidence interval (CI) = (0.70–0.89) which was significantly better than urinary WBC count (AUC = 0.70, 95% CI = [0.59–0.82], P = 0.042) as isolated test. Conclusions We have demonstrated the diagnostic value of urinary N-glycosylation profiling, which shows great potential as biomarker for prostatitis. Further research is required to unravel the developmental course of prostatic inflammation. PMID:26526330

Prostatitis - acute

MedlinePlus

... and Bennett's Principles and Practice of Infectious Diseases, Updated Edition . 8th ed. Philadelphia, PA: Elsevier Saunders; 2015: ... information/urologic-diseases/prostate-problems/prostatitis-inflammation-prostate . Updated July 2014. Accessed September 27, 2017. Review Date ...

[Prostate histopathology of NIH category IV prostatitis detected by sextant prostate needle biopsy from the patients with high prostatic specific antigen].

PubMed

Shimomura, Tatsuya; Kiyota, Hiroshi; Takahashi, Hiroyuki; Madarame, Jun; Kimura, Takahiro; Onodera, Shouichi

2003-08-01

Asymptomatic prostatitis is classified as category IV in NIH classification of prostatitis syndrome (1999). No report concerning this category has been present. We investigated this category histopathologically and clinically, in order to clarify the histopathological distribution and its correlation to the clinical features, in this study. Among 785 patients who were suspected prostate cancer because of their high prostatic specific antigen (PSA) values and to have a sextant prostate needle biopsy was performed between January, 1996 and December, 2000, 88 patients (11.2%) were diagnosed as NIH category IV prostatitis (asymptomatic prostatitis). We observed all pathological specimens stained with Hematoxylin-Eosine, and classified them into subtypes according to the classification criteria for prostatitis defined by True et al. (1999). We also investigated the relationship between histopathological distribution and clinical features such as PSA values, PSA density, the incidence of pyuria or bacteriuria. In the histopathological study, grade distributions were 12.5% (11/88) in mild, 71.6% (63/88) in moderate, and 15.9% (14/88) in severe. Location distributions were 2.3% (2/88) in glandular, 68.2% (60/88) in periglandular, and 29.5% (26/88) in stromal. No relationship between these subtypes and clinical features was recognized statistically. However, 7 patients (7.95%) were diagnosed as prostate cancers, later. Pyuria was found in 29.1% (23/79). Bacteriuria was present in 14.3% (11/77). Isolated bacteria were 4 strains of Enterococcus faccalis, 2 strains of each of Pseudomonas aeruginosa and Staphylococcus aureus, and one strain of each of Escherichia coli, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Staphylococcus haemolyticus, and Staphylococcus epidermidis. Gram positive rod, and Candida sp. No relationship between these subtypes and bacterial species was recognized. These results indicated that the incidence of NIII category IV prostatits

Detecting prostate cancer and prostatic calcifications using advanced magnetic resonance imaging.

PubMed

Dou, Shewei; Bai, Yan; Shandil, Ankit; Ding, Degang; Shi, Dapeng; Haacke, E Mark; Wang, Meiyun

2017-01-01

Prostate cancer and prostatic calcifications have a high incidence in elderly men. We aimed to investigate the diagnostic capabilities of susceptibility-weighted imaging in detecting prostate cancer and prostatic calcifications. A total number of 156 men, including 34 with prostate cancer and 122 with benign prostate were enrolled in this study. Computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging, and susceptibility-weighted imaging were performed on all the patients. One hundred and twelve prostatic calcifications were detected in 87 patients. The sensitivities and specificities of the conventional magnetic resonance imaging, apparent diffusion coefficient, and susceptibility-filtered phase images in detecting prostate cancer and prostatic calcifications were calculated. McNemar's Chi-square test was used to compare the differences in sensitivities and specificities between the techniques. The results showed that the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic cancer were greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). In addition, the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic calcifications were comparable to that of computed tomography and greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). Given the high incidence of susceptibility-weighted imaging (SWI) abnormality in prostate cancer, we conclude that susceptibility-weighted imaging is more sensitive and specific than conventional magnetic resonance imaging, diffusion-weighted imaging, and computed tomography in detecting prostate cancer. Furthermore, susceptibility-weighted imaging can identify prostatic calcifications similar to computed tomography, and it is much better than conventional magnetic resonance imaging and diffusion-weighted imaging.

Malakoplakia of the Prostate as a Mimicker of Prostate Cancer on Prostate Health Index and Magnetic Resonance Imaging-Fusion Prostate Biopsy: A Case Report.

PubMed

Heah, Nathaniel H; Tan, Teck Wei; Tan, Yung Khan

2017-01-01

Background: Isolated malakoplakia of the prostate is a rare inflammatory condition that has been clinically mistaken for prostatic malignancies. The development of Prostate Imaging Reporting and Data System (PI-RADS) classifications, and Prostate Health Index (PHI) has led to more accurate diagnosis of clinically significant disease and stratification of patients that may be at risk of prostate cancer. Case Presentation: We present a case of a 75-year-old male who was on follow-up with our hospital for elevated prostate specific antigen (PSA). He was admitted for an episode of urosepsis, which was treated with antibiotics and subsequently underwent further workup and was found to have a raised PHI, as well as a high PI-RADS classification and was later found to have malakoplakia based on histology of prostate tissue obtained during targeted magnetic resonance imaging (MRI)-guided fusion prostate biopsy. Conclusion: To our understanding, this is the first case where a prostate lesion has been labeled as a PI-RADS 5 lesion, with elevated PHI that has subsequently been proven histologically to be malakoplakia. An important possible confounder is the interval between the MRI and the episode of urosepsis and it is well known that urosepsis can affect the PSA and MRI result. We present this case to highlight the potential for a false diagnosis of prostate cancer, in spite of laboratory and radiological findings.

γ-Oryzanol reduces caveolin-1 and PCGEM1 expression, markers of aggressiveness in prostate cancer cell lines.

PubMed

Hirsch, Gabriela E; Parisi, Mariana M; Martins, Leo A M; Andrade, Claudia M B; Barbé-Tuana, Florencia M; Guma, Fátima T C R

2015-06-01

Prostate cancer is a leading cause of death among men due to the limited number of treatment strategies available for advanced disease. γ-oryzanol is a component of rice bran, rich in phytosterols, known for its antioxidant, anti-carcinogenic and endocrinological effects. It is known that γ-oryzanol may affect prostate cancer cells through the down regulation of the antioxidant genes and that phytosterols have anti-proliferative and apoptotic effects. There are evidences showing that some of the components of γ-oryzanol can modulate genes involved in the development and progression of prostate cancer, as caveolin-1 (Cav-1) and prostate specific androgen-regulated gene (PCGEM1). To determine the effects of γ-oryzanol on prostate cancer cell survival we evaluated the cell viability and biomass by MTT and sulforhodamine B assays, respectively. Cell death, cell cycle and pERK1/2 activity were assessed by flow cytometry. The changes in gene expression involved in the survival and progression of prostate cancer cav-1 and PCGEM1 genes were evaluated by quantitative real time reverse transcriptase polymerase chain reaction (RT-PCR) and cav-1 protein by immunofluorescence followed by confocal microscopy analysis. We found that γ-oryzanol decreases cell viability and culture biomass by apoptosis and/or necrosis death in androgen unresponsive (PC3 and DU145) and responsive (LNCaP) cell lines, and signals through pERK1/2 in LNCaP and DU145 cells. γ-oryzanol also appears to block cell cycle progression at the G2/M in PC3 and LNCaP cells and at G0/G1 in DU145 cells. These effects were accompanied by a down regulation in the expression of the cav-1 in both androgen unresponsive cell lines and PCGEM1 gene in DU145 and LNCaP cells. In summary, we used biochemical and genetics approaches to demonstrate that γ-oryzanol show a promising adjuvant role in the treatment of prostate cancer. © 2015 Wiley Periodicals, Inc.

MRI target delineation may reduce long-term toxicity after prostate radiotherapy.

PubMed

Sander, Lotte; Langkilde, Niels Christian; Holmberg, Mats; Carl, Jesper

2014-06-01

Aiming for minimal toxicity after radical prostate cancer (PC) radiotherapy (RT), magnetic resonance imaging (MRI) target delineation could be a possible benefit knowing that clinical target volumes (CTV) are up to 30% smaller, when CTV delineation on MRI is compared to standard computed tomography (CT). This study compares long-term toxicity using CT or MRI delineation before PC RT. Urinary and rectal toxicity assessments 36 months after image-guided RT (78 Gy) using CTC-AE scores in two groups of PC patients. Peak symptom score values were registered. One group of patients (n=72) had standard CT target delineation and gold markers as fiducials. Another group of patients (n=73) had MRI target delineation and a nickel-titanium stent as fiducial. At 36 months no difference in overall survival (92% in both groups, p=0.29) or in PSA-relapse free survival was found between the groups (MRI=89% and CT=94%, p=0.67). A significantly smaller CTV was found in the MRI group (p=0.02). Urinary retention and frequency were significantly reduced in the MRI group (p=0.03 in the matter of both). The overall urinary and rectal toxicity did not differ between the two groups. MRI delineation leads to a significantly reduced CTV. Significantly lower urinary frequency and urinary retention toxicity scores were observed following MRI delineation. The study did not find significant differences in overall urinary or rectal toxicity between the two groups. PSA-relapse survival did not differ between the two groups at 36 months.

Prostate Diseases

MedlinePlus

... Home › Aging & Health A to Z › Prostate Diseases Font size A A A Print Share Glossary Basic ... body. Approximately 3 million American men have some type of prostate disease. The most common prostate diseases ...

Prostate Diseases

MedlinePlus

The prostate is a gland in men. It helps make semen, the fluid that contains sperm. The prostate surrounds the tube that carries urine away from the bladder and out of the body. A young man's prostate is ...

Effect of obese and lean Zucker rat sera on human and rat prostate cancer cells: implications in obesity-related prostate tumor biology.

PubMed

Lamarre, Neil S; Ruggieri, Michael R; Braverman, Alan S; Gerstein, Matthew I; Mydlo, Jack H

2007-01-01

Several reports have demonstrated the effects of obesity on prostate cancer. Also several reports have linked expression of vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (FGF-2) to prostate cancer aggressiveness. The objective of this study was to determine whether a difference exists between lean and obese Zucker rat sera on proliferation prostate cancer cell lines, as well as to examine the differences in FGF-2 and VEGF concentrations. Ten-week-old female obese and lean Zucker rat sera were subjected to charcoal stripping and tested for the proliferation of human LNCaP and rat AT3B-1 prostate cancer cells. An acetonitrile extract of the charcoal used to strip the sera was also tested for mitogenicity. VEGF and FGF-2 concentrations were determined by enzyme-linked immunosorbent assay. Both unstripped and charcoal-stripped obese rat sera had a greater mitogenic effect than did the lean sera on the LNCaP cell line. Charcoal stripping of both obese and lean sera reduced the mitogenic effect on the AT3B-1 cell line. The acetonitrile extract of the charcoal used to strip the sera was unable to recover this proliferative effect. The concentration of VEGF was greater in the obese serum than in the lean serum, and charcoal stripping reduced the concentrations of both FGF-2 and VEGF. The finding of greater VEGF in obese rat sera, as well as greater mitogenic responses on human prostate cancer cells in vitro, suggests this as one of the many possible mechanisms involved in obesity-related prostate cancer biology.

Allium™ TPS--A New Prostatic Stent for the Treatment of Patients with Benign Prostatic Obstruction: The First Report.

PubMed

Yildiz, Guner; Bahouth, Zaher; Halachmi, Sarel; Meyer, Gil; Nativ, Ofer; Moskovitz, Boaz

2016-03-01

Several prostatic stents were developed in the last three decades, none of which were able to provide a real alternative in patients unfit or unwilling to undergo classical prostatic surgeries. In this study, we report the results of the use of a newly developed prostatic stent--the Allium™ Triangular Prostatic Stent (TPS). The Allium TPS is a highly flexible, nitinol-built polymer-covered stent, which prevents tissue ingrowth and reduces encrustations. Between 2008 and 2014, at two centers (Israel and Turkey), the stent was inserted under local or regional anesthesia in 51 patients with benign prostatic obstruction (BPO) who are unwilling or unfit for surgery. Patients were followed for 12 months from surgery. The primary outcome was symptom improvement as measured by the international prostate symptom score (IPSS) and improvement in peak urinary flow. Stent insertion was successful in all patients. The mean IPSS decreased from 26.4 to 7.7 on the last follow-up. The mean peak flow increased from 5.5 mL/second before stent insertion to 16.0 mL/second 1 year thereafter. The main adverse effect was transient pain in nine patients. No stent migration or obstruction was seen. Patients reported satisfaction and improvement in quality of life. Our short-term results show that Allium TPS is safe and effective for the treatment of patients with BPO.

Enteric-coated, highly standardized cranberry extract reduces risk of UTIs and urinary symptoms during radiotherapy for prostate carcinoma

PubMed Central

Bonetta, Alberto; Di Pierro, Francesco

2012-01-01

Background Cranberry (Vaccinium macrocarpon) proanthocyanidins can interfere with adhesion of bacteria to uroepithelial cells, potentially preventing lower urinary tract infections (LUTIs). Because LUTIs are a common side effect of external beam radiotherapy (EBRT) for prostate cancer, we evaluated the clinical efficacy of enteric-coated tablets containing highly standardized V. msacrocarpon (ecVM) in this condition. Methods A total of 370 consecutive patients were entered into this study. All patients received intensity-modulated radiotherapy for prostate cancer; 184 patients were also treated with ecVM while 186 served as controls. Cranberry extract therapy started on the simulation day, at which time a bladder catheterization was performed. During EBRT (over 6–7 weeks), all patients underwent weekly examination for urinary tract symptoms, including regular urine cultures during the treatment period. Results Compliance was excellent, with no adverse effects or allergic reactions being observed, apart from gastric pain in two patients. In the cranberry cohort (n = 184), 16 LUTIs (8.7%) were observed, while in the control group (n = 186) 45 LUTIs (24.2%) were recorded. This difference was statistically significant. Furthermore, lower rates of nocturia, urgency, micturition frequency, and dysuria were observed in the group that received cranberry extract. Conclusion Cranberry extracts have been reported to reduce the incidence of LUTIs significantly in women and children. Our data extend these results to patients with prostate cancer undergoing irradiation to the pelvis, who had a significant reduction in LUTIs compared with controls. These results were accompanied by a statistically significant reduction in urinary tract symptoms (dysuria, nocturia, urinary frequency, urgency), suggesting a generally protective effect of cranberry extract on the bladder mucosa. PMID:22977312

Detecting prostate cancer and prostatic calcifications using advanced magnetic resonance imaging

PubMed Central

Dou, Shewei; Bai, Yan; Shandil, Ankit; Ding, Degang; Shi, Dapeng; Haacke, E Mark; Wang, Meiyun

2017-01-01

Prostate cancer and prostatic calcifications have a high incidence in elderly men. We aimed to investigate the diagnostic capabilities of susceptibility-weighted imaging in detecting prostate cancer and prostatic calcifications. A total number of 156 men, including 34 with prostate cancer and 122 with benign prostate were enrolled in this study. Computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging, and susceptibility-weighted imaging were performed on all the patients. One hundred and twelve prostatic calcifications were detected in 87 patients. The sensitivities and specificities of the conventional magnetic resonance imaging, apparent diffusion coefficient, and susceptibility-filtered phase images in detecting prostate cancer and prostatic calcifications were calculated. McNemar's Chi-square test was used to compare the differences in sensitivities and specificities between the techniques. The results showed that the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic cancer were greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). In addition, the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic calcifications were comparable to that of computed tomography and greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). Given the high incidence of susceptibility-weighted imaging (SWI) abnormality in prostate cancer, we conclude that susceptibility-weighted imaging is more sensitive and specific than conventional magnetic resonance imaging, diffusion-weighted imaging, and computed tomography in detecting prostate cancer. Furthermore, susceptibility-weighted imaging can identify prostatic calcifications similar to computed tomography, and it is much better than conventional magnetic resonance imaging and diffusion-weighted imaging. PMID:27004542

Differentiation of prostatitis and prostate cancer using the Prostate Imaging-Reporting and Data System (PI-RADS).

PubMed

Meier-Schroers, Michael; Kukuk, Guido; Wolter, Karsten; Decker, Georges; Fischer, Stefan; Marx, Christian; Traeber, Frank; Sprinkart, Alois Martin; Block, Wolfgang; Schild, Hans Heinz; Willinek, Winfried

2016-07-01

To determine if prostate cancer (PCa) and prostatitis can be differentiated by using PI-RADS. 3T MR images of 68 patients with 85 cancer suspicious lesions were analyzed. The findings were correlated with histopathology. T2w imaging (T2WI), diffusion weighted imaging (DWI), dynamic contrast enhancement (DCE), and MR-Spectroscopy (MRS) were acquired. Every lesion was given a single PI-RADS score for each parameter, as well as a sum score and a PI-RADS v2 score. Furthermore, T2-morphology, ADC-value, perfusion type, citrate/choline-level, and localization were evaluated. 44 of 85 lesions showed PCa (51.8%), 21 chronic prostatitis (24.7%), and 20 other benign tissue such as hyperplasia or fibromuscular tissue (23.5%). The single PI-RADS score for T2WI, DWI, DCE, as well as the aggregated score including and not including MRS, and the PI-RADS v2-score were all significantly higher for PCa than for prostatitis or other tissue (p<0.001). The single PI-RADS score for MRS and the PI-RADS sum score including MRS were significantly higher for prostatitis than for other tissue (p=0.029 and p=0.020), whereas the other parameters were not different. Prostatitis usually presented borderline pathological PI-RADS scores, showed restricted diffusion with ADC≥900mm(2)/s in 100% of cases, was more often indistinctly hypointense on T2WI (66.7%), and localized in the transitional zone (57.1%). An ADC≥900mm(2)/s achieved the highest predictive value for prostatitis (AUC=0.859). Prostatitis can be differentiated from PCa using PI-RADS, since all available parameters are more distinct in cases of cancer. However, there is significant overlap between prostatitis and other benign findings, thus PI-RADS is only suitable to a limited extent for the primary assessment of prostatitis. Restricted diffusion with ADC≥900mm(2)/s is believed to be a good indicator for prostatitis. MRS can help to distinguish between prostatitis and other tissue. Copyright © 2016 Elsevier Ireland Ltd. All

Sonoelastographic evaluation with the determination of compressibility ratio for symmetrical prostatic regions in the diagnosis of clinically significant prostate cancer

PubMed Central

Słapa, Rafał Z.; Jakubowski, Wiesław S.; Migda, Bartosz; Dmowski, Tadeusz

2014-01-01

Aim Sonoelastography is a technique that assesses tissue hardness/compressibility. Utility and sensitivity of the method in prostate cancer diagnostics were assessed compared to the current gold standard in prostate cancer diagnostics i.e. systematic biopsy. Material and methods The study involved 84 patients suspected of prostate cancer based on elevated PSA levels or abnormal per rectal examination findings. Sonoelastography was used to evaluate the prostate gland. In the case of regions with hardness two-fold greater than that of symmetric prostate area (strain ratio >2), targeted biopsy was used; which was followed by an ultrasound-guided 8- or 10-core systematic biopsy (regardless of sonoelastography-indicated sites) as a reference point. Results The mean age of patients was 69 years. PSA serum levels ranged between 1.02 and 885 ng/dl. The mean prostate volume was 62 ml (19–149 ml). Prostate cancer was found in 39 out of 84 individuals. Statistically significant differences in strain ratios between cancers and benign lesions were shown. Sonoelastography guided biopsy revealed 30 lesions – overall sensitivity 77% (sensitivity of the method – 81%). Sonoelastographic sensitivity increased depending on cancer stage according to the Gleason grading system: 6–60%, 7–75%, 8–83%, 9/10–100%. The estimated sensitivity of systematic biopsy was 92%. Conclusions Sonoelastography shows higher diagnostic sensitivity in prostate cancer diagnostics compared to conventional imaging techniques, i.e. grey-scale TRUS, Doppler ultrasound. It allows to reduce the number of collected tissue cores, and thus limit the incidence of complications as well as the costs involved. Sonoelastography using the determination of compressibility ratio for symmetrical prostatic regions may prove useful in the detection of clinically significant prostate cancer. PMID:26674065

Effect of ethanolic extract of Lepidium meyenii Walp on serum hormone levels in ovariectomized rats

PubMed Central

Zhang, Yongzhong; Yu, Longjiang; Jin, Wenwen; Ao, Mingzhang

2014-01-01

Objective: To evaluate the effect of long-term ethanol extract of Lepidium meyenii (Maca) on serum hormone levels in ovariectomized (OVX) rats and compare them with the effect of diethylstilbestrol. Materials and Methods: Fifty female Sprague-Dawley rats were ovariectomized or sham operated. Both sham and OVX control groups (n = 10, respectively) received the vehicle. The remaining OVX rats were oral administrated with ethanol extract of Maca (0.096, or 0.24g/kg; n = 10, respectively) and diethylstilbestrol (0.05 mg/kg; n = 10). The treatment continued for 28 weeks. At week 12 and week 28, the blood of rats was collected and serum hormone levels, including estradiol (E2), testosterone (T) and follicle-stimulating hormone (FSH) were measured by radioimmunoassay. Results: At week 12, the levels of serum E2 were slightly higher in Maca groups than that in OVX group; T levels were significantly decreased; and FSH levels were advanced slightly in Maca groups than that in sham group. After 28 weeks administration, serum E2 levels in Maca-treated animals did not differ significantly from sham control, the low dose of Maca increased serum E2 levels, and Maca prevented increase in serum FSH levels compared with OVX group. Conclusions: Long-term Maca supply modulates endocrine hormone balance in OVX rats, especially it decreases enhanced FSH levels. It is proposed that Maca may become a potential choice for postmenopausal women. PMID:25097281

Optical coherence tomography of the prostate nerves

NASA Astrophysics Data System (ADS)

Chitchian, Shahab

Preservation of the cavernous nerves during prostate cancer surgery is critical in preserving a man's ability to have spontaneous erections following surgery. These microscopic nerves course along the surface of the prostate within a few millimeters of the prostate capsule, and they vary in size and location from one patient to another, making preservation of the nerves difficult during dissection and removal of a cancerous prostate gland. These observations may explain in part the wide variability in reported sexual potency rates (9--86%) following prostate cancer surgery. Any technology capable of providing improved identification, imaging, and visualization of the cavernous nerves during prostate cancer surgery would be of great assistance in improving sexual function after surgery, and result in direct patient benefit. Optical coherence tomography (OCT) is a noninvasive optical imaging technique capable of performing high-resolution cross-sectional in vivo and in situ imaging of microstructures in biological tissues. OCT imaging of the cavernous nerves in the rat and human prostate has recently been demonstrated. However, improvements in the OCT system and the quality of the images for identification of the cavernous nerves is necessary before clinical use. The following chapters describe complementary approaches to improving identification and imaging of the cavernous nerves during OCT of the prostate gland. After the introduction to OCT imaging of the prostate gland, the optimal wavelength for deep imaging of the prostate is studied in Chapter 2. An oblique-incidence single point measurement technique using a normal-detector scanning system was implemented to determine the absorption and reduced scattering coefficients, mua and m's , of fresh canine prostate tissue, ex vivo, from the diffuse reflectance profile of near-IR light as a function of source-detector distance. The effective attenuation coefficient, mueff, and the Optical Penetration Depth (OPD) were

Current status of 5α-reductase inhibitors in prostate disease management.

PubMed

Kang, Dong Il; Chung, Jae Il

2013-04-01

The key enzyme in the androgen synthesis and androgen receptor pathways is 5α-reductase (5-AR), which occurs as three isoenzymes. Types I and II 5-ARs the most important clinically, and two different 5-AR inhibitors (5-ARIs), finasteride and dutasteride, have been developed. Several urology associations have recommended and upgraded the use of 5-ARIs for an enlarged prostate with lower urinary tract symptoms. In the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events Trial, 5-ARIs reduced the incidence of low-grade prostate cancer. However, despite the documented reductions in the overall incidence of prostate cancer, 5-ARIs are at the center of a dispute. The American Society of Clinical Oncology (ASCO) and the American Urology Association (AUA) presented clinical guidelines for the use of 5-ARIs for chemoprevention of prostate cancer in 2008. However, ASCO/AUA has eliminated these from the main "Clinical Guidelines" in 2012, because the U.S. Food and Drug Administration denied a supplemental New Drug Application for the use of dutasteride for prostate cancer chemoprevention. The 5-ARIs can also be used to manage hemospermia and prostatic hematuria, and to prevent intraoperative bleeding, although there is insufficient evidence for a standard strategy. This review summarizes the current use of 5-ARIs for prostate disease, including benign prostate hyperplasia, prostate cancer, prostate-related bleeding, and hemospermia.

[MRI and prostate cancer: a paradigm shift].

PubMed

Lemaitre, L; Rouvière, O; Penna-Renard, R; Villers, A; Puech, P

2008-09-01

A shift in the use of prostate MR for diagnosis, staging, and pre-treatment planning over the last several years has modified the MR protocols. Classically used to detect extra-prostatic tumor, MR now plays a role for diagnosis (pre-biopsy evaluation in a patient with elevated PSA and suspected cancer in an unusual site), treatment planning (prostate mapping), and follow-up after treatment (evaluation for local recurrence or follow-up after HIFU, radiation therapy, or focal treatment...). Imaging protocols at 1.5T and 3.0T combine morphological T2W imaging with functional sequences (perfusion imaging, diffusion imaging, spectroscopy) using high-resolution phased array pelvic coils or "combined" coils (added endorectal coil). To promote acceptance by clinicians and increased access to patients, the indications for prostate MR must be better defined (and provide useful data to urologists), the cost must be reduced, and results must be more reproducible and standardized.

Lower urinary tract symptoms in benign prostatic hyperplasia patients: orchestrated by chronic prostatic inflammation and prostatic calculi?.

PubMed

Kim, Sang Hoon; Jung, Kyu In; Koh, Jun Sung; Min, Ki Ouk; Cho, Su Yeon; Kim, Hyun Woo

2013-01-01

This study aims to examine the relationship between chronic prostatic inflammation and prostatic calculi, and clinical parameters of benign prostatic hyperplasia (BPH). This study was based on 225 patients who underwent transurethral resection of the prostate for BPH. Chronic inflammation was graded as 0 (n = 44), I (n = 54), II (n = 88) or III (n = 39) according to severity. Prostatic calculi were classified into types A (n = 66), B (n = 44), M (n = 77) and N (n = 38). The relationship between inflammation and calculus type was analyzed, and clinical parameters of BPH were compared for each group. There was no correlation between severity of inflammation and calculus type. Prostatic volume increased with the severity of inflammation and showed significant differences between G2, G3 and G0. The International Prostate Symptom Score also increased with increasing inflammation. There was no significant difference between each clinical parameter according to calculus type. Prostatic calculi had no significant association with chronic inflammation and clinical parameters of BPH. Chronic inflammation was associated with the volume of the prostate and storage symptoms; thus, it is not only presumed to be related to the progression of BPH, but may also be one of the causes of lower urinary tract symptoms. Copyright © 2012 S. Karger AG, Basel.

Essential Roles of Epithelial Bone Morphogenetic Protein Signaling During Prostatic Development

PubMed Central

Omori, Akiko; Miyagawa, Shinichi; Ogino, Yukiko; Harada, Masayo; Ishii, Kenichiro; Sugimura, Yoshiki; Ogino, Hajime; Nakagata, Naomi

2014-01-01

Prostate is a male sex-accessory organ. The prostatic epithelia consist primarily of basal and luminal cells that differentiate from embryonic urogenital sinus epithelia. Prostate tumors are believed to originate in the basal and luminal cells. However, factors that promote normal epithelial differentiation have not been well elucidated, particularly for bone morphogenetic protein (Bmp) signaling. This study shows that Bmp signaling prominently increases during prostatic differentiation in the luminal epithelia, which is monitored by the expression of phosphorylated Smad1/5/8. To elucidate the mechanism of epithelial differentiation and the function of Bmp signaling during prostatic development, conditional male mutant mouse analysis for the epithelial-specific Bmp receptor 1a (Bmpr1a) was performed. We demonstrate that Bmp signaling is indispensable for luminal cell maturation, which regulates basal cell proliferation. Expression of the prostatic epithelial regulatory gene Nkx3.1 was significantly reduced in the Bmpr1a mutants. These results indicate that Bmp signaling is a key factor for prostatic epithelial differentiation, possibly by controlling the prostatic regulatory gene Nkx3.1. PMID:24731097

Prostate-specific antigen lowering effect of metabolic syndrome is influenced by prostate volume.

PubMed

Choi, Woo Suk; Heo, Nam Ju; Paick, Jae-Seung; Son, Hwancheol

2016-04-01

To investigate the influence of metabolic syndrome on prostate-specific antigen levels by considering prostate volume and plasma volume. We retrospectively analyzed 4111 men who underwent routine check-ups including prostate-specific antigen and transrectal ultrasonography. The definition of metabolic syndrome was based on the modified Adult Treatment Panel III criteria. Prostate-specific antigen mass density (prostate-specific antigen × plasma volume / prostate volume) was calculated for adjusting plasma volume and prostate volume. We compared prostate-specific antigen and prostate-specific antigen mass density levels of participants with metabolic syndrome (metabolic syndrome group, n = 1242) and without metabolic syndrome (non-prostate-specific antigen metabolic syndrome group, n = 2869). To evaluate the impact of metabolic syndrome on prostate-specific antigen, linear regression analysis for the natural logarithm of prostate-specific antigen was used. Patients in the metabolic syndrome group had significantly older age (P < 0.001), larger prostate volume (P < 0.001), higher plasma volume (P < 0.001) and lower mean serum prostate-specific antigen (non-metabolic syndrome group vs metabolic syndrome group; 1.22 ± 0.91 vs 1.15 ± 0.76 ng/mL, P = 0.006). Prostate-specific antigen mass density in the metabolic syndrome group was still significantly lower than that in the metabolic syndrome group (0.124 ± 0.084 vs 0.115 ± 0.071 μg/mL, P = 0.001). After adjusting for age, prostate volume and plasma volume using linear regression model, the presence of metabolic syndrome was a significant independent factor for lower prostate-specific antigen (prostate-specific antigen decrease by 4.1%, P = 0.046). Prostate-specific antigen levels in patients with metabolic syndrome seem to be lower, and this finding might be affected by the prostate volume. © 2016 The Japanese Urological Association.

Quantitative diffusion MRI using reduced field-of-view and multi-shot acquisition techniques: Validation in phantoms and prostate imaging.

PubMed

Zhang, Yuxin; Holmes, James; Rabanillo, Iñaki; Guidon, Arnaud; Wells, Shane; Hernando, Diego

2018-09-01

To evaluate the reproducibility of quantitative diffusion measurements obtained with reduced Field of View (rFOV) and Multi-shot EPI (msEPI) acquisitions, using single-shot EPI (ssEPI) as a reference. Diffusion phantom experiments, and prostate diffusion-weighted imaging in healthy volunteers and patients with known or suspected prostate cancer were performed across the three different sequences. Quantitative diffusion measurements of apparent diffusion coefficient, and diffusion kurtosis parameters (healthy volunteers), were obtained and compared across diffusion sequences (rFOV, msEPI, and ssEPI). Other possible confounding factors like b-value combinations and acquisition parameters were also investigated. Both msEPI and rFOV have shown reproducible quantitative diffusion measurements relative to ssEPI; no significant difference in ADC was observed across pulse sequences in the standard diffusion phantom (p = 0.156), healthy volunteers (p ≥ 0.12) or patients (p ≥ 0.26). The ADC values within the non-cancerous central gland and peripheral zone of patients were 1.29 ± 0.17 × 10 -3  mm 2 /s and 1.74 ± 0.23 × 10 -3  mm 2 /s respectively. However, differences in quantitative diffusion parameters were observed across different number of averages for rFOV, and across b-value groups and diffusion models for all the three sequences. Both rFOV and msEPI have the potential to provide high image quality with reproducible quantitative diffusion measurements in prostate diffusion MRI. Copyright © 2018 Elsevier Inc. All rights reserved.

Characteristic fingerprinting based on macamides for discrimination of maca (Lepidium meyenii) by LC/MS/MS and multivariate statistical analysis.

PubMed

Pan, Yu; Zhang, Ji; Li, Hong; Wang, Yuan-Zhong; Li, Wan-Yi

2016-10-01

Macamides with a benzylalkylamide nucleus are characteristic and major bioactive compounds in the functional food maca (Lepidium meyenii Walp). The aim of this study was to explore variations in macamide content among maca from China and Peru. Twenty-seven batches of maca hypocotyls with different phenotypes, sampled from different geographical origins, were extracted and profiled by liquid chromatography with ultraviolet detection/tandem mass spectrometry (LC-UV/MS/MS). Twelve macamides were identified by MS operated in multiple scanning modes. Similarity analysis showed that maca samples differed significantly in their macamide fingerprinting. Partial least squares discriminant analysis (PLS-DA) was used to differentiate samples according to their geographical origin and to identify the most relevant variables in the classification model. The prediction accuracy for raw maca was 91% and five macamides were selected and considered as chemical markers for sample classification. When combined with a PLS-DA model, characteristic fingerprinting based on macamides could be recommended for labelling for the authentication of maca from different geographical origins. The results provided potential evidence for the relationships between environmental or other factors and distribution of macamides. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Radiosensitization in prostate cancer: mechanisms and targets

PubMed Central

2013-01-01

Prostate cancer is the second most commonly diagnosed cancer in American men over the age of 45 years and is the third most common cause of cancer related deaths in American men. In 2012 it is estimated that 241,740 men will be diagnosed with prostate cancer and 28,170 men will succumb to prostate cancer. Currently, radiation therapy is one of the most common definitive treatment options for localized prostate cancer. However, significant number of patients undergoing radiation therapy will develop locally persistent/recurrent tumours. The varying response rates to radiation may be due to 1) tumor microenvironment, 2) tumor stage/grade, 3) modality used to deliver radiation, and 4) dose of radiation. Higher doses of radiation has not always proved to be effective and have been associated with increased morbidity. Compounds designed to enhance the killing effects of radiation, radiosensitizers, have been extensively investigated over the past decade. The development of radiosensitizing agents could improve survival, improve quality of life and reduce costs, thus benefiting both patients and healthcare systems. Herin, we shall review the role and mechanisms of various agents that can sensitize tumours, specifically prostate cancer. PMID:23351141

Testosterone and the Prostate.

PubMed

Tan, Ronny B W; Silberstein, Jonathan L; Hellstrom, Wayne J G

2014-10-01

Late-onset hypogonadism, lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE), and prostate cancer commonly coexist in the aging male. Due to a better understanding of the physiology and impact of testosterone on benign and malignant diseases of the prostate, the view toward testosterone replacement therapy (TRT) in these individuals has changed dramatically over time. This communication evaluates the effects of testosterone on benign prostatic growth and prostate cancer and reviews the evidence for TRT for men with BPE and prostate cancer. A literature review was performed with regards to TRT in men with prostate cancer as well as the effect of testosterone on the growth of benign prostate tissue and prostate cancer carcinogenesis. To evaluate the evidence for an effect of testosterone on the growth of benign prostate tissue and the development of prostate cancer and TRT in men with prostate cancer. TRT does not exacerbate LUTS. Current evidence is lacking but suggests that TRT may not increase the risk of subsequent diagnosis of prostate cancer, and is unlikely to impact recurrence or progression for men with treated prostate cancer, but longer follow-up is needed. There is no evidence to suggest that TRT is contraindicated in men with BPE or effectively treated prostate cancer. Tan RBW, Silberstein JL, and Hellstrom WJG. Testosterone and the prostate. Sex Med Rev 2014;2:112-120. Copyright © 2014 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Prostate-specific membrane antigen PET/MRI validation of MR textural analysis for detection of transition zone prostate cancer.

PubMed

Bates, Anthony; Miles, Kenneth

2017-12-01

To validate MR textural analysis (MRTA) for detection of transition zone (TZ) prostate cancer through comparison with co-registered prostate-specific membrane antigen (PSMA) PET-MR. Retrospective analysis was performed for 30 men who underwent simultaneous PSMA PET-MR imaging for staging of prostate cancer. Thirty texture features were derived from each manually contoured T2-weighted, transaxial, prostatic TZ using texture analysis software that applies a spatial band-pass filter and quantifies texture through histogram analysis. Texture features of the TZ were compared to PSMA expression on the corresponding PET images. The Benjamini-Hochberg correction controlled the false discovery rate at <5%. Eighty-eight T2-weighted images in 18 patients demonstrated abnormal PSMA expression within the TZ on PET-MR. 123 images were PSMA negative. Based on the corrected p-value of 0.005, significant differences between PSMA positive and negative slices were found for 16 texture parameters: Standard deviation and mean of positive pixels for all spatial filters (p = <0.0001 for both at all spatial scaling factor (SSF) values) and mean intensity following filtration for SSF 3-6 mm (p = 0.0002-0.0018). Abnormal expression of PSMA within the TZ is associated with altered texture on T2-weighted MR, providing validation of MRTA for the detection of TZ prostate cancer. • Prostate transition zone (TZ) MR texture analysis may assist in prostate cancer detection. • Abnormal transition zone PSMA expression correlates with altered texture on T2-weighted MR. • TZ with abnormal PSMA expression demonstrates significantly reduced MI, SD and MPP.

New treatments for localized prostate cancer.

PubMed

Marberger, Michael; Carroll, Peter R; Zelefsky, Michael J; Coleman, Jonathan A; Hricak, Hedvig; Scardino, Peter T; Abenhaim, Lucien L

2008-12-01

cryotherapy, focal HIFU should reduce the adverse sexual, urinary, and bowel effects of whole gland ablation. New techniques are being developed to allow HIFU treatment under real-time guidance using magnetic resonance imaging, which could improve the precision and reduce the adverse effects further. Another promising technique, currently in clinical trials, is vascular-targeted photodynamic therapy, which has been used for whole gland ablation of locally recurrent cancer after radiotherapy and, more recently, for focal ablation of previously untreated cancer. In combination with a new, systemically administered photodynamic agent, laser light is delivered through fibers introduced into the prostate under ultrasound guidance. This technique does not heat the prostate but destroys the endothelial cells and cancer by activating the photodynamic agent. Damage to surrounding structures appears to be limited and can be controlled by the duration and intensity of the light. We have reviewed the principles of focal therapy and these new therapeutic modalities.

Prostate health index (PHI) and prostate-specific antigen (PSA) predictive models for prostate cancer in the Chinese population and the role of digital rectal examination-estimated prostate volume.

PubMed

Chiu, Peter K F; Roobol, Monique J; Teoh, Jeremy Y; Lee, Wai-Man; Yip, Siu-Ying; Hou, See-Ming; Bangma, Chris H; Ng, Chi-Fai

2016-10-01

To investigate PSA- and PHI (prostate health index)-based models for prediction of prostate cancer (PCa) and the feasibility of using DRE-estimated prostate volume (DRE-PV) in the models. This study included 569 Chinese men with PSA 4-10 ng/mL and non-suspicious DRE with transrectal ultrasound (TRUS) 10-core prostate biopsies performed between April 2008 and July 2015. DRE-PV was estimated using 3 pre-defined classes: 25, 40, or 60 ml. The performance of PSA-based and PHI-based predictive models including age, DRE-PV, and TRUS prostate volume (TRUS-PV) was analyzed using logistic regression and area under the receiver operating curves (AUC), in both the whole cohort and the screening age group of 55-75. PCa and high-grade PCa (HGPCa) was diagnosed in 10.9 % (62/569) and 2.8 % (16/569) men, respectively. The performance of DRE-PV-based models was similar to TRUS-PV-based models. In the age group 55-75, the AUCs for PCa of PSA alone, PSA with DRE-PV and age, PHI alone, PHI with DRE-PV and age, and PHI with TRUS-PV and age were 0.54, 0.71, 0.76, 0.78, and 0.78, respectively. The corresponding AUCs for HGPCa were higher (0.60, 0.70, 0.85, 0.83, and 0.83). At 10 and 20 % risk threshold for PCa, 38.4 and 55.4 % biopsies could be avoided in the PHI-based model, respectively. PHI had better performance over PSA-based models and could reduce unnecessary biopsies. A DRE-assessed PV can replace TRUS-assessed PV in multivariate prediction models to facilitate clinical use.

Intraepithelial lymphocytes in relation to NIH category IV prostatitis in autopsy prostate.

PubMed

Dikov, Dorian; Bachurska, Svitlana; Staikov, Dimitri; Sarafian, Victoria

2015-07-01

Quantitative analysis of the number, normal and pathologic ratios between lymphocytes and epithelial cells (ECs), and the significance of intraepithelial lymphocytes (IELs) in normal prostatic epithelium, benign prostatic hyperplasia (BPH), and high grade prostatic intraepithelial neoplasia (PIN) in relation to NIH category IV prostatitis (histologic prostatitis: HP) was studied in autopsy prostate. IELs were analysed in 59 autopsy prostates, which was routinely embedded in paraffin and immunohistochemically stained for CD3. An average of 300-500 ECs were counted per case. The number of IELs was calculated as the mean/100 ECs. Category IV prostatitis was evaluated using NIH consensus grading system in terms of anatomical localization and grade. In healthy individuals the mean number of IELs/100 ECs was 0.61 ± 0.34% or ≤1 lymphocyte/100 ECs, which is considered as the normal basal level of prostate IELs. In category IV prostatitis, the mean number of IELs/100 ECs was 8.53 ± 3.25% or 5-11 lymphocytes/100 ECs. The number of IELs in both around and inside inflammation areas correlated to the grade and location of HP (P < 0.0001 and P < 0.0003), the presence of acute glandular inflammation (P < 0.0001), the scattered stromal lymphocytes (P = 0.029), and BPH and PIN associated prostatic inflammation (P < 0.0001). The study presents the first attempt to examine and score the basic quantitative values of prostatic IELs in normal prostate and in relation to category IV prostatitis. The detected normal upper limit of CD3+ IELs is 1 lymphocyte/100 ECs in the normal prostate epithelium. This is considered as an organ specific characteristic of the prostate-associated lymphoid tissue (PALT). Values >5 IELs/100 ECs indicate the presence of category IV prostatitis. The severity of inflammation correlates to the number of IELs. There is an intimate link between the quantity of the IELs, the degree of the severity and the localization of category IV

Holmium laser enucleation of the prostate and retropubic prostatic adenomectomy: morbidity analysis and anesthesia considerations.

PubMed

Soto-Mesa, D; Amorín-Díaz, M; Pérez-Arviza, L; Fernández-Pello Montes, S; Martín-Huéscar, A

2015-11-01

Holmium laser enucleation of the prostate (HoLEP) is an alternative to prostatic adenomectomy for the surgical treatment of benign prostatic hypertrophy. We analyzed our learning curve for this technique, and we compared it in a secondary manner with prostatic adenomectomy. A retrospective comparative study was conducted that included the first 100 cases of HoLEP performed in our center and the latest 50 cases of retropubic adenomectomy. We collected data on the patients, the surgery, the anesthesia, the perioperative variables, the anesthesia complications and the postoperative variables, with a 6-month follow-up. We analyzed the learning curve without mentors for HoLEP and compared the characteristics of HoLEP in 2 separate phases (learning and stabilization phases) with the latest retropubic prostatic adenomectomies performed. Intradural anesthesia was the most common technique. The transfusion needs, length of stay (P<.01) and postoperative morbidity were lower for HoLEP than for adenomectomy. However, the retropubic adenomectomy group had larger initial prostate volumes (P<.001) and shorter surgical times (P<.001). Better surgical performance (P<.001) and a lower incidence of complications were observed in the HoLEP-B group (once the learning curve had been overcome) compared with the HoLEP-A group. In our center, HoLEP was introduced as a valid alternative to open retropubic adenomectomy, with excellent results in terms of morbidity and reduced hospital stay. In terms of the learning curve, we consider that approximately 50 patients (without mentor) is an appropriate cutoff. Local anesthesia is a good choice for the anesthesia technique. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Graminex Pollen: Phenolic Pattern, Colorimetric Analysis and Protective Effects in Immortalized Prostate Cells (PC3) and Rat Prostate Challenged with LPS.

PubMed

Locatelli, Marcello; Macchione, Nicola; Ferrante, Claudio; Chiavaroli, Annalisa; Recinella, Lucia; Carradori, Simone; Zengin, Gokhan; Cesa, Stefania; Leporini, Lidia; Leone, Sheila; Brunetti, Luigi; Menghini, Luigi; Orlando, Giustino

2018-05-11

Prostatitis, a general term describing prostate inflammation, is a common disease that could be sustained by bacterial or non-bacterial infectious agents. The efficacy of herbal extracts with antioxidant and anti-inflammatory effects for blunting the burden of inflammation and oxidative stress, with possible improvements in clinical symptoms, is under investigation. Pollen extracts have been previously reported as promising agents in managing clinical symptoms related to prostatitis. The aim of the present work was to evaluate the protective effects of Graminex pollen (Graminex TM , Deshler, OH, USA), a commercially available product based on standardized pollen extracts, in rat prostate specimens, ex vivo. In this context, we studied the putative mechanism of action of pollen on multiple inflammatory pathways, including the reduction of prostaglandin E₂ (PGE₂), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and malondialdehyde (MDA), whose activities were significantly increased by inflammatory stimuli. We characterized by means of chromatographic and colorimetric studies the composition of Graminex pollen to better correlate the activity of pollen on immortalized prostate cells (PC3), and in rat prostate specimens challenged with Escherichia coli lipopolysaccharide (LPS). We found that Graminex pollen was able to reduce radical oxygen species (ROS) production by PC3 cells and MDA, NFκB mRNA, and PGE₂ levels, in rat prostate specimens. According to our experimental evidence, Graminex pollen appears to be a promising natural product for the management of the inflammatory components in the prostate.

Effect of Tripterygium Wilfordii Polyglycoside on Experimental Prostatitis Caused by Ureaplasma Urealyticum in Rats

PubMed Central

Shan, Pingnan; Lu, Zhiyong; Ye, Lihong; Fang, Yaqin; Tan, Suhong; Xuan, Guohong; Ru, Jincheng; Mao, Liming

2016-01-01

Background Prostatitis is a common and refractory urological disease with complicated etiology. Ureaplasma urealyticum (UU) has a close relationship with human urinary tract infection that can induce nonbacterial prostatitis. Tripterygium wilfordii polyglycoside (TWP) is a non-steroidal immune inhibitor that causes significant immune suppression and anti-inflammatory effects. Its role in prostatitis caused by UU has not yet been established. The aim of this study was to investigate the effect of TWP on UU-infected prostatitis in a rat model. Material/Methods UU-infected prostatitis SD model rats were randomly divided into 2 groups: the prostatitis group (model group) and the TWP treatment group (treatment group). At 7 days after treatment, prostate weight, leucocyte count, lecithin corpuscles, UU infection rate, and UU microbe count were compared between the 2 groups. Serum inflammatory cytokines TNF-α was determined by ELISA, and ICAM-1 and NF-κB expression were detected. Results UU infection rate was 80% after modeling. The rat prostate weight and leucocyte count in the model group increased significantly, while lecithin corpuscles decreased. Compared with controls, inflammatory factor TNF-α, ICAM-1, and NF-κB expression were obviously higher (P<0.05). TWP markedly reduced prostate weight and leucocyte count, increased lecithin corpuscles, and decreased UU microbe count and TNF-α, ICAM-1, and NF-κB expression (P<0.05). Conclusions TWP can inhibit expression of inflammatory factors and may be useful in treating UU-infected prostatitis through reducing UU infection rate. PMID:27743513

Effect of Tripterygium Wilfordii Polyglycoside on Experimental Prostatitis Caused by Ureaplasma Urealyticum in Rats.

PubMed

Shan, Pingnan; Lu, Zhiyong; Ye, Lihong; Fang, Yaqin; Tan, Suhong; Xuan, Guohong; Ru, Jincheng; Mao, Liming

2016-10-15

BACKGROUND Prostatitis is a common and refractory urological disease with complicated etiology. Ureaplasma urealyticum (UU) has a close relationship with human urinary tract infection that can induce nonbacterial prostatitis. Tripterygium wilfordii polyglycoside (TWP) is a non-steroidal immune inhibitor that causes significant immune suppression and anti-inflammatory effects. Its role in prostatitis caused by UU has not yet been established. The aim of this study was to investigate the effect of TWP on UU-infected prostatitis in a rat model. MATERIAL AND METHODS UU-infected prostatitis SD model rats were randomly divided into 2 groups: the prostatitis group (model group) and the TWP treatment group (treatment group). At 7 days after treatment, prostate weight, leucocyte count, lecithin corpuscles, UU infection rate, and UU microbe count were compared between the 2 groups. Serum inflammatory cytokines TNF-α was determined by ELISA, and ICAM-1 and NF-κB expression were detected. RESULTS UU infection rate was 80% after modeling. The rat prostate weight and leucocyte count in the model group increased significantly, while lecithin corpuscles decreased. Compared with controls, inflammatory factor TNF-α, ICAM-1, and NF-κB expression were obviously higher (P<0.05). TWP markedly reduced prostate weight and leucocyte count, increased lecithin corpuscles, and decreased UU microbe count and TNF-α, ICAM-1, and NF-κB expression (P<0.05). CONCLUSIONS TWP can inhibit expression of inflammatory factors and may be useful in treating UU-infected prostatitis through reducing UU infection rate.

Influence of Antiflatulent Dietary Advice on Intrafraction Motion for Prostate Cancer Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lips, Irene M., E-mail: I.M.Lips@umcutrecht.nl; Kotte, Alexis N.T.J.; Gils, Carla H. van

Purpose: To evaluate the effect of an antiflatulent dietary advice on the intrafraction prostate motion in patients treated with intensity-modulated radiotherapy (IMRT) for prostate cancer. Methods and Materials: Between February 2002 and December 2009, 977 patients received five-beam IMRT for prostate cancer to a dose of 76 Gy in 35 fractions combined with fiducial markers for position verification. In July 2008, the diet, consisting of dietary guidelines to obtain regular bowel movements and to reduce intestinal gas by avoiding certain foods and air swallowing, was introduced to reduce the prostate motion. The intrafraction prostate movement was determined from the portalmore » images of the first segment of all five beams. Clinically relevant intrafraction motion was defined as {>=}50% of the fractions with an intrafraction motion outside a range of 3 mm. Results: A total of 739 patients were treated without the diet and 105 patients were treated with radiotherapy after introduction of the diet. The median and interquartile range of the average intrafraction motion per patient was 2.53 mm (interquartile range, 2.2-3.0) without the diet and 3.00 mm (interquartile range, 2.4-3.5) with the diet (p < .0001). The percentage of patients with clinically relevant intrafraction motion increased statistically significant from 19.1% without diet to 42.9% with a diet (odds ratio, 3.18; 95% confidence interval, 2.07-4.88; p < .0001). Conclusions: The results of the present study suggest that antiflatulent dietary advice for patients undergoing IMRT for prostate cancer does not reduce the intrafraction movement of the prostate. Therefore, antiflatulent dietary advice is not recommended in clinical practice for this purpose.« less

Influence of the neural microenvironment on prostate cancer.

PubMed

Coarfa, Christian; Florentin, Diego; Putluri, NagiReddy; Ding, Yi; Au, Jason; He, Dandan; Ragheb, Ahmed; Frolov, Anna; Michailidis, George; Lee, MinJae; Kadmon, Dov; Miles, Brian; Smith, Christopher; Ittmann, Michael; Rowley, David; Sreekumar, Arun; Creighton, Chad J; Ayala, Gustavo

2018-02-01

Nerves are key factors in prostate cancer (PCa), but the functional role of innervation in prostate cancer is poorly understood. PCa induced neurogenesis and perineural invasion (PNI), are associated with aggressive disease. We denervated rodent prostates chemically and physically, before orthotopically implanting cancer cells. We also performed a human neoadjuvant clinical trial using botulinum toxin type A (Botox) and saline in the same patient, before prostatectomy. Bilateral denervation resulted in reduced tumor incidence and size in mice. Botox treatment in humans resulted in increased apoptosis of cancer cells in the Botox treated side. A similar denervation gene array profile was identified in tumors arising in denervated rodent prostates, in spinal cord injury patients and in the Botox treated side of patients. Denervation induced exhibited a signature gene profile, indicating translation and bioenergetic shutdown. Nerves also regulate basic cellular functions of non-neoplastic epithelial cells. Nerves play a role in the homeostasis of normal epithelial tissues and are involved in prostate cancer tumor survival. This study confirms that interactions between human cancer and nerves are essential to disease progression. This work may make a major impact in general cancer treatment strategies, as nerve/cancer interactions are likely important in other cancers as well. Targeting the neural microenvironment may represent a therapeutic approach for the treatment of human prostate cancer. © 2017 The Authors. The Prostate Published by Wiley Periodicals, Inc.

Treating the Problem Prostate

MedlinePlus

... this page please turn JavaScript on. Feature: Prostate Enlargement Treating the Problem Prostate Past Issues / Winter 2017 ... Don't put it off." Read More "Prostate Enlargement" Articles Treating the Problem Prostate / Understanding Prostate Enlargement / ...

New laser treatment approaches for benign prostatic hyperplasia.

PubMed

Fried, Nathaniel M

2007-01-01

The recent introduction of higher power 100 W holmium:yttrium-aluminum-garnet (Ho:YAG) and 80 W potassium titanyl phosphate lasers for rapid incision and vaporization of the prostate has resulted in renewed interest in the use of lasers for treatment of benign prostatic hyperplasia (BPH). Although long-term studies are still lacking, short-term results demonstrate that these procedures are at least as safe and effective in relieving BPH symptoms as transurethral resection of the prostate and may provide reduced morbidity. Other laser techniques, such as interstitial laser coagulation and contact laser vaporization of the prostate, have lost popularity due to complications with increased catheterization time, irritative symptoms, and infection rates. Although Ho:YAG laser enucleation of the prostate is more difficult to learn and a slower procedure than potassium titanyl phosphate laser vaporization, the Ho:YAG laser is currently the most proven laser technique for BPH treatment. This article reviews the latest developments in laser treatment of BPH over the past 2 years and provides a view toward the future of lasers in the treatment of BPH.

Statin and NSAID Use and Prostate Cancer Risk

PubMed Central

Coogan, Patricia F.; Kelly, Judith Parsells; Strom, Brian L.; Rosenberg, Lynn

2010-01-01

Purpose Some studies have reported reduced risks of advanced, but not early, prostate cancer among statin users, and one study found a reduced risk only among statin users who had also used nonsteroidal anti-inflammatory drugs (NSAIDs). We have previously reported no association between statin use and prostate cancer in our hospital-based Case Control Surveillance Study. The purpose of the present analyses was to update the findings by cancer stage and to evaluate the joint use of statins and NSAIDs. Methods Cases were 1367 men with prostate cancer and controls were 2007 men with diagnoses unrelated to statin or NSAID use. We used multivariable logistic regression analyses to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for statin use compared with no use, and joint use of statin and NSAIDs compared with use of neither. Results The odds ratio among regular statin users was 1.1 (95% CI 0.9–1.5), and odds ratios were similar among early and late stage cancers. The odds ratio among joint statin and NSAID users was 1.1 (95% CI 0.7–1.6). Conclusion The present results do not support a protective effect of statin use, or statin and NSAID use, on the risk of advanced prostate cancer. PMID:20582910

The therapeutic potential of royal jelly in benign prostatic hyperplasia. Comparison with contemporary literature.

PubMed

Pajovic, Bogdan; Radojevic, Nemanja; Dimitrovski, Antonio; Tomovic, Savo; Vukovic, Marko

2016-09-01

The aim of this study is to establish the scientific benefit of royal jelly (RJ) on prostatic-specific antigen (PSA), post-void residual (PVR) volume and International Prostate Symptom Score (IPSS) in benign prostatic hyperplasia. For the study, a group of 40 men were administered 38 mg of RJ over a period of three months, their PSA values, prostate volumes and the volumes of their transitory prostate zones, PVR and IPPS values were measured at the end of the first month, and at the end of the third month. The results of this study confirm the potential of RJ in reducing PSA scores and improving IPSS values. Since the use of RJ did not lead to any significant reduction in PVR, prostate volume, or to any involution of the transitory zone, it appears that it may only affect the blood marker of prostatic hyperplasia and to improve quality-of-life (QoL) in those patients. Overall, in comparison to phytotherapy and conventional therapy, RJ had similar positive effects on QoL in patients with BPH, however it exhibited markedly better effects on reducing PSA levels in blood. The therapeutical use of RJ exhibited no side effects.

Microbiological Characteristics of Acute Prostatitis After Transrectal Prostate Biopsy

PubMed Central

Bang, Jun-Ho; Choe, Hyun-Sop; Lee, Dong-Sup; Lee, Seung-Ju

2013-01-01

Purpose We aimed to identify microbiological characteristics in patients with acute prostatitis after transrectal prostate biopsy to provide guidance in the review of prevention and treatment protocols. Materials and Methods A retrospective analysis of medical records was performed in 1,814 cases who underwent prostate biopsy at Seoul St. Mary's Hospital and St. Vincent's Hospital over a 5 year period from 2006 to 2011. Cases in which acute prostatitis occurred within 7 days after the biopsy were investigated. Before starting treatment with antibiotics, sample collections were done for culture of urine and blood. Culture and drug susceptibility was identified by use of a method established by the Clinical and Laboratory Standards Institute. Results A total of 1,814 biopsy procedures were performed in 1,541 patients. For 1,246 patients, the procedure was the first biopsy, whereas for 295 patients it was a repeat biopsy. Twenty-one patients (1.36%) were identified as having acute bacterial prostatitis after the biopsy. Fifteen patients (1.2%) had acute prostatitis after the first biopsy, and 6 patients (2.03%) experienced acute prostatitis after a repeat biopsy. Even though the incidence of acute bacterial prostatitis was higher after repeat biopsy than that after the first biopsy, there was no statistically significant intergroup difference in terms of incidence (χ2=1.223, p=0.269). When the collected urine and blood samples were cultured, Escherichia coli was found in samples from 15 patients (71.4%), Klebsiella pneumoniae in 3 patients (14.3%), Enterobacter intermedius in 1 patient (4.8%), E. aerogenes in 1 patient (4.8%), and Pseudomonas aeruginosa in 1 patient (4.8%). A fluoroquinolone-resistant strain was confirmed in 5 cases (23.8%) in total. Three cases of E. coli and 1 case of Klebsiella had extended-spectrum β-lactamase activity. Conclusions Empirical treatment of acute prostatitis should be done with consideration of geographical prevalence and drug

The polyphosphate–factor XII pathway drives coagulation in prostate cancer-associated thrombosis

PubMed Central

Nickel, Katrin F.; Ronquist, Göran; Langer, Florian; Labberton, Linda; Fuchs, Tobias A.; Bokemeyer, Carsten; Sauter, Guido; Graefen, Markus; Mackman, Nigel; Stavrou, Evi X.; Ronquist, Gunnar

2015-01-01

Cancer is a leading cause of thrombosis. We identify a new procoagulant mechanism that contributes to thromboembolism in prostate cancer and allows for safe anticoagulation therapy development. Prostate cancer-mediated procoagulant activity was reduced in plasma in the absence of factor XII or its substrate of the intrinsic coagulation pathway factor XI. Prostate cancer cells and secreted prostasomes expose long chain polyphosphate on their surface that colocalized with active factor XII and initiated coagulation in a factor XII-dependent manner. Polyphosphate content correlated with the procoagulant activity of prostasomes. Inherited deficiency in factor XI or XII or high-molecular-weight kininogen, but not plasma kallikrein, protected mice from prostasome-induced lethal pulmonary embolism. Targeting polyphosphate or factor XII conferred resistance to prostate cancer-driven thrombosis in mice, without increasing bleeding. Inhibition of factor XII with recombinant 3F7 antibody reduced the increased prostasome-mediated procoagulant activity in patient plasma. The data illustrate a critical role for polyphosphate/factor XII-triggered coagulation in prostate cancer-associated thrombosis with implications for anticoagulation without therapy-associated bleeding in malignancies. PMID:26153520

Modified madigan prostatectomy: a procedure preserved prostatic urethra intact.

PubMed

Lu, Jun; Ye, Zhangqun; Hu, Weilie

2005-01-01

A total of 92 patients with benign prostatic hyperplasia (BPH) were subjected to modified Madigan prostatectomy (MPC) for a much satisfactory effect in open prostatectomy surgery. Exposing anterior prostatic urethra near the bladder neck and conjunct cystotomy modified the MPC procedure. This modified procedure preserved prostatic urethra intact and could also deal with intracystic lesions at the same time. The intact of prostatic urethra was kept completely or largely in 86 cases. The amount of blood loss during modified procedure was less. The mean operative time was 105 min. Seventy patients had been followed up for 3-24 months. The postoperative average Qmax was 19. 2 ml/s. The cystourethrography revealed that the urethra and bladder neck were intact in 10 patients postoperatively. Furthermore, the prostatic urethra was obviously wider after modified MPC. The modified MPC can reduce the occurrence of urethra injury and enlarge the MPC indications. The modified technique is easy to perform with less complications and much satisfactory clinical result.

Characterization of adenoviral transduction profile in prostate cancer cells and normal prostate tissue.

PubMed

Ai, Jianzhong; Tai, Phillip W L; Lu, Yi; Li, Jia; Ma, Hong; Su, Qin; Wei, Qiang; Li, Hong; Gao, Guangping

2017-09-01

Prostate diseases are common in males worldwide with high morbidity. Gene therapy is an attractive therapeutic strategy for prostate diseases, however, it is currently underdeveloped. As well known, adeno virus (Ad) is the most widely used gene therapy vector. The aims of this study are to explore transduction efficiency of Ad in prostate cancer cells and normal prostate tissue, thus further providing guidance for future prostate pathophysiological studies and therapeutic development of prostate diseases. We produced Ad expressing enhanced green fluorescence protein (EGFP), and characterized the transduction efficiency of Ad in both human and mouse prostate cancer cell lines in vitro, as well as prostate tumor xenograft, and wild-type mouse prostate tissue in vivo. Ad transduction efficiency was determined by EGFP fluorescence using microscopy and flow cytometry. Cell type-specific transduction was examined by immunofluorescence staining of cell markers. Our data showed that Ad efficiently transduced human and mouse prostate cancer cells in vitro in a dose dependent manner. Following intratumoral and intraprostate injection, Ad could efficiently transduce prostate tumor xenograft and the major prostatic cell types in vivo, respectively. Our findings suggest that Ad can efficiently transduce prostate tumor cells in vitro as well as xenograft and normal prostate tissue in vivo, and further indicate that Ad could be a potentially powerful toolbox for future gene therapy of prostate diseases. © 2017 Wiley Periodicals, Inc.

A System Dynamics Model of Serum Prostate-Specific Antigen Screening for Prostate Cancer.

PubMed

Palma, Anton; Lounsbury, David W; Schlecht, Nicolas F; Agalliu, Ilir

2016-02-01

Since 2012, US guidelines have recommended against prostate-specific antigen (PSA) screening for prostate cancer. However, evidence of screening benefit from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening trial and the European Randomized Study of Screening for Prostate Cancer has been inconsistent, due partly to differences in noncompliance and contamination. Using system dynamics modeling, we replicated the PLCO trial and extrapolated follow-up to 20 years. We then simulated 3 scenarios correcting for contamination in the PLCO control arm using Surveillance, Epidemiology, and End Results (SEER) incidence and survival data collected prior to the PSA screening era (scenario 1), SEER data collected during the PLCO trial period (1993-2001) (scenario 2), and data from the European trial's control arm (1991-2005) (scenario 3). In all scenarios, noncompliance was corrected using incidence and survival rates for men with screen-detected cancer in the PLCO screening arm. Scenarios 1 and 3 showed a benefit of PSA screening, with relative risks of 0.62 (95% confidence interval: 0.53, 0.72) and 0.70 (95% confidence interval: 0.59, 0.83) for cancer-specific mortality after 20 years, respectively. In scenario 2, however, there was no benefit of screening. This simulation showed that after correcting for noncompliance and contamination, there is potential benefit of PSA screening in reducing prostate cancer mortality. It also demonstrates the utility of system dynamics modeling for synthesizing epidemiologic evidence to inform public policy. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Inhibition effects of chlorogenic acid on benign prostatic hyperplasia in mice.

PubMed

Huang, Ya; Chen, Huaguo; Zhou, Xin; Wu, Xingdong; Hu, Enming; Jiang, Zhengmeng

2017-08-15

This study aimed to evaluate the inhibitory effects and explore mechanisms of chlorogenic acid against testosterone-induced benign prostatic hyperplasia (BPH) in mice. Benign prostatic hyperplasia model was induced in experimental groups by daily subcutaneous injections of testosterone propionate (7.5mg/kg/d) consecutively for 14 d. A total of 60 mice were randomly divided into six groups: (Group 1) normal control group, (Group 2) benign prostatic hyperplasia model control group, (Group 3) benign prostatic hyperplasia mice treated with finasteride at a dose of 1mg/kg, (Group 4) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 0.8mg/kg (low dose group), (Group 5) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 1.6mg/kg (medium dose group) and (Group 6) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 3.2mg/kg (high dose group). Animals were sacrificed on the scheduled termination, pick out the eyeball to get blood, then prostates were weighed and prostatic index were determined. Then the serum acid phosphatase (ACP), prostatic acid phosphatase (PACP) and typeⅡ5-alpha-reductase (SRD5A2) levels were measured and observed morphological changes of the prostate. Comparing with benign prostatic hyperplasia model group, the high and medium dose of chlorogenic acid could significantly reduce prostate index and levels of acid phosphatase, prostatic acid phosphatase and typeⅡ5-alpha-reductase (P<0.05 or P<0.01). These findings were supported by histopathological observations of prostate tissues. Histopathological examination also indicated that chlorogenic acid treatment at the high and medium doses inhibited testosterone-induced prostatic hyperplasia. The results indicated that chlorogenic acid exhibited restraining effect on benign prostatic hyperplasia model animals, and its mechanism might be related to inhibit typeⅡ5-alpha reductase activity. Copyright © 2017

Elevation of SHARPIN Protein Levels in Prostate Adenocarcinomas Promotes Metastasis and Impairs Patient Survivals.

PubMed

Huang, Hai; Du, Tao; Zhang, Yiming; Lai, Yiming; Li, Kaiwen; Fan, Xinxing; Zhu, Dingjun; Lin, Tianxin; Xu, Kewei; Huang, Jian; Liu, Leyuan; Guo, Zhenghui

2017-05-01

SHARPIN, SHANK-associated RH domain interacting protein, associates with a linear ubiquitin chain assembly complex (LUBAC) to regulate inflammation and immunity. It has been reported that SHARPIN is highly expressed in several human tumors including ovarian cancer and liver cancer. We found that SHARPIN is also highly expressed in prostate cancer cell lines of DU145, LNCAP, and PC-3. Suppression of SHARPIN caused an inhibition of NF-κB signal and decreases in tumorigenesis of cultured cells in NOD/SCID mouse model. Overexpression of SHARPIN in prostate cancer cells promoted cell growth and reduced apoptosis through NF-kB/ERK/Akt pathway and apoptosis-associated proteins. We analyzed the expression of SHARPIN in prostate cancer tissues from 95 patients and its relationship with other clinical characteristics associated with PCA malignancies and patient survivals, and examined the impacts of SHARPIN suppression with siRNA on proliferation, angiogenesis, invasion, and expression levels of MMP-9 of prostate cancer cells and metastasis to lung by these cells in nude mice. High levels of SHARPIN were associated with high malignancies of PCA and predicted shorter survivals of PCA patients. Suppression of SHARPIN impaired cell proliferation, angiogenesis, and invasion and reduced levels of MMP-9 in prostate cancer cells and reduced the size of metastatic lung tumors induced by these cells in mice. SHARPIN enhances the metastasis of prostate cancer and impair patient survivals. Prostate 77:718-728, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Exogenous fatty acid binding protein 4 promotes human prostate cancer cell progression.

PubMed

Uehara, Hisanori; Takahashi, Tetsuyuki; Oha, Mina; Ogawa, Hirohisa; Izumi, Keisuke

2014-12-01

Epidemiologic studies have found that obesity is associated with malignant grade and mortality in prostate cancer. Several adipokines have been implicated as putative mediating factors between obesity and prostate cancer. Fatty acid binding protein 4 (FABP4), a member of the cytoplasmic fatty acid binding protein multigene family, was recently identified as a novel adipokine. Although FABP4 is released from adipocytes and mean circulating concentrations of FABP4 are linked with obesity, effects of exogenous FABP4 on prostate cancer progression are unclear. In this study, we examined the effects of exogenous FABP4 on human prostate cancer cell progression. FABP4 treatment promoted serum-induced prostate cancer cell invasion in vitro. Furthermore, oleic acid promoted prostate cancer cell invasion only if FABP4 was present in the medium. These promoting effects were reduced by FABP4 inhibitor, which inhibits FABP4 binding to fatty acids. Immunostaining for FABP4 showed that exogenous FABP4 was taken up into DU145 cells in three-dimensional culture. In mice, treatment with FABP4 inhibitor reduced the subcutaneous growth and lung metastasis of prostate cancer cells. Immunohistochemical analysis showed that the number of apoptotic cells, positive for cleaved caspase-3 and cleaved PARP, was increased in subcutaneous tumors of FABP4 inhibitor-treated mice, as compared with control mice. These results suggest that exogenous FABP4 might promote human prostate cancer cell progression by binding with fatty acids. Additionally, exogenous FABP4 activated the PI3K/Akt pathway, independently of binding to fatty acids. Thus, FABP4 might be a key molecule to understand the mechanisms underlying the obesity-prostate cancer progression link. © 2014 UICC.

The Complex Interplay Between Cholesterol and Prostate Malignancy

PubMed Central

Solomon, Keith R.; Freeman, Michael R.

2011-01-01

Research into the topic of the role of cholesterol and prostate disease has been ongoing for many years, however our mechanistic and translational understanding is still poor. Recent evidence indicates that cholesterol lowering drugs reduce the risk of aggressive prostate cancer, however the studies in this area, performed over many years, reflect much controversy and uncertainty. Here we explore the entire literature on the relationship between circulating cholesterol and prostate cancer, with consideration and criticism of the older as well as the newer studies. We consider why low cholesterol is associated with both increased and decreased risk of advanced prostate cancer, and explain why both observations are probably correct. We discuss the conflicting results of randomized placebo-controlled trials of statin drugs vs. observational studies and demonstrate that a predominance of pravastatin in the randomized trials paints a distorted view of statin effects. Lastly, we discuss new data suggesting that a critical aspect of the role of cholesterol in prostate cancer progression is through its role in intratumoral steroidogenesis. With these points addressed, the data strongly point to hypercholesterolemia as a risk factor for prostate cancer progression and suggest clinical opportunities for the use of cholesterol lowering therapies to alter disease course. PMID:21798387

AgNOR histochemical expression in benign prostatic hyperplasia and prostatic adenocarcinoma

NASA Astrophysics Data System (ADS)

Rita, R.; Delyuzar; Laksmi, L. I.

2018-03-01

Benign prostatic hyperplasia and prostatic adenocarcinoma were common diseases and usually occurred after the 5th decade of life. The problem in diagnosing using Hematoxylin and Eosin staining was how to differentiate whether it is benign or malignant zone. Therefore, proliferating markers, such as AgNOR, could be helping to over this difficulty. A descriptive study using consecutive sampling as the method of sample recruiting was conducted to describe AgNOR histochemical expression in benign prostatic hyperplasia and prostatic adenocarcinoma. AgNOR staining was done in 13 benign prostatic hyperplasia samples and 7 prostatic adenocarcinoma samples, which have been confirmed using p63 immunohistochemical staining before. Benign prostatic hyperplasia usually showed lower AgNOR proliferating activity while all of theprostatic adenocarcinoma (100%) had high AgNOR proliferating activity.

A multiresolution prostate representation for automatic segmentation in magnetic resonance images.

PubMed

Alvarez, Charlens; Martínez, Fabio; Romero, Eduardo

2017-04-01

Accurate prostate delineation is necessary in radiotherapy processes for concentrating the dose onto the prostate and reducing side effects in neighboring organs. Currently, manual delineation is performed over magnetic resonance imaging (MRI) taking advantage of its high soft tissue contrast property. Nevertheless, as human intervention is a consuming task with high intra- and interobserver variability rates, (semi)-automatic organ delineation tools have emerged to cope with these challenges, reducing the time spent for these tasks. This work presents a multiresolution representation that defines a novel metric and allows to segment a new prostate by combining a set of most similar prostates in a dataset. The proposed method starts by selecting the set of most similar prostates with respect to a new one using the proposed multiresolution representation. This representation characterizes the prostate through a set of salient points, extracted from a region of interest (ROI) that encloses the organ and refined using structural information, allowing to capture main relevant features of the organ boundary. Afterward, the new prostate is automatically segmented by combining the nonrigidly registered expert delineations associated to the previous selected similar prostates using a weighted patch-based strategy. Finally, the prostate contour is smoothed based on morphological operations. The proposed approach was evaluated with respect to the expert manual segmentation under a leave-one-out scheme using two public datasets, obtaining averaged Dice coefficients of 82% ± 0.07 and 83% ± 0.06, and demonstrating a competitive performance with respect to atlas-based state-of-the-art methods. The proposed multiresolution representation provides a feature space that follows a local salient point criteria and a global rule of the spatial configuration among these points to find out the most similar prostates. This strategy suggests an easy adaptation in the clinical

Stromal androgen receptor roles in the development of normal prostate, benign prostate hyperplasia, and prostate cancer.

PubMed

Wen, Simeng; Chang, Hong-Chiang; Tian, Jing; Shang, Zhiqun; Niu, Yuanjie; Chang, Chawnshang

2015-02-01

The prostate is an androgen-sensitive organ that needs proper androgen/androgen receptor (AR) signals for normal development. The progression of prostate diseases, including benign prostate hyperplasia (BPH) and prostate cancer (PCa), also needs proper androgen/AR signals. Tissue recombination studies report that stromal, but not epithelial, AR plays more critical roles via the mesenchymal-epithelial interactions to influence the early process of prostate development. However, in BPH and PCa, much more attention has been focused on epithelial AR roles. However, accumulating evidence indicates that stromal AR is also irreplaceable and plays critical roles in prostate disease progression. Herein, we summarize the roles of stromal AR in the development of normal prostate, BPH, and PCa, with evidence from the recent results of in vitro cell line studies, tissue recombination experiments, and AR knockout animal models. Current evidence suggests that stromal AR may play positive roles to promote BPH and PCa progression, and targeting stromal AR selectively with AR degradation enhancer, ASC-J9, may allow development of better therapies with fewer adverse effects to battle BPH and PCa. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Evaluation of [-2] proPSA and Prostate Health Index (phi) for the detection of prostate cancer: a systematic review and meta-analysis.

PubMed

Filella, Xavier; Giménez, Nuria

2013-04-01

The usefulness of %[-2] proPSA and Prostate Health Index (phi) in the detection of prostate cancer are currently unknown. It has been suggested that these tests can distinguish prostate cancer from benign prostatic diseases better than PSA or %fPSA. We performed a systematic review and meta-analysis of the available scientific evidence to evaluate the clinical usefulness of %[-2] proPSA and phi. Relevant published papers were identified by searching computerized bibliographic systems. Data on sensitivity and specificity were extracted from 12 studies: 10 studies about %[-2] proPSA (3928 patients in total, including 1762 with confirmed prostate cancer) and eight studies about phi (2919 patients in total, including 1515 with confirmed prostate cancer). The sensitivity for the detection of prostate cancer was 90% for %[-2] proPSA and phi, while the pooled specificity was 32.5% (95% CI 30.6-34.5) and 31.6% (95% CI 29.2-34.0) for %[-2] proPSA and phi, respectively. The measurement of %[-2] proPSA improves the accuracy of prostate cancer detection in comparison with PSA or %fPSA, particularly in the group of patients with PSA between 2 μg/L and 10 μg/L. Similar results were obtained measuring phi. Using these tests, it is possible to reduce the number of unnecessary biopsies, maintaining a high cancer detection rate. Published results also showed that %[-2] proPSA and phi are related to the aggressiveness of the tumor.

Discoveries and application of prostate-specific antigen, and some proposals to optimize prostate cancer screening.

PubMed

Tokudome, Shinkan; Ando, Ryosuke; Koda, Yoshiro

2016-01-01

The discoveries and application of prostate-specific antigen (PSA) have been much appreciated because PSA-based screening has saved millions of lives of prostate cancer (PCa) patients. Historically speaking, Flocks et al first identified antigenic properties in prostate tissue in 1960. Then, Barnes et al detected immunologic characteristics in prostatic fluid in 1963. Hara et al characterized γ-semino-protein in semen in 1966, and it has been proven to be identical to PSA. Subsequently, Ablin et al independently reported the presence of precipitation antigens in the prostate in 1970. Wang et al purified the PSA in 1979, and Kuriyama et al first applied an enzyme-linked immunosorbent assay for PSA in 1980. However, the positive predictive value with a cutoff figure of 4.0 ng/mL appeared substantially low (∼30%). There are overdiagnoses and overtreatments for latent/low-risk PCa. Controversies exist in the PCa mortality-reducing effects of PSA screening between the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. For optimizing PCa screening, PSA-related items may require the following: 1) adjustment of the cutoff values according to age, as well as setting limits to age and screening intervals; 2) improving test performance using doubling time, density, and ratio of free: total PSA; and 3) fostering active surveillance for low-risk PCa with monitoring by PSA value. Other items needing consideration may include the following: 1) examinations of cell proliferation and cell cycle markers in biopsy specimens; 2) independent quantification of Gleason grading; 3) developing ethnicity-specific staging nomograms based on tumor stage, PSA value, and Gleason score; 4) delineation of the natural history; 5) revisiting the significance of the androgen/testosterone hypothesis; and 6) devoting special attention to individuals with a certain genetic predisposition. Finally

Boosting antitumor responses of T lymphocytes infiltrating human prostate cancers

PubMed Central

Bronte, Vincenzo; Kasic, Tihana; Gri, Giorgia; Gallana, Keti; Borsellino, Giovanna; Marigo, Ilaria; Battistini, Luca; Iafrate, Massimo; Prayer-Galetti, Tommaso; Pagano, Francesco; Viola, Antonella

2005-01-01

Immunotherapy may provide valid alternative therapy for patients with hormone-refractory metastatic prostate cancer. However, if the tumor environment exerts a suppressive action on antigen-specific tumor-infiltrating lymphocytes (TIL), immunotherapy will achieve little, if any, success. In this study, we analyzed the modulation of TIL responses by the tumor environment using collagen gel matrix–supported organ cultures of human prostate carcinomas. Our results indicate that human prostatic adenocarcinomas are infiltrated by terminally differentiated cytotoxic T lymphocytes that are, however, in an unresponsive status. We demonstrate the presence of high levels of nitrotyrosines in prostatic TIL, suggesting a local production of peroxynitrites. By inhibiting the activity of arginase and nitric oxide synthase, key enzymes of L-arginine metabolism that are highly expressed in malignant but not in normal prostates, reduced tyrosine nitration and restoration of TIL responsiveness to tumor were achieved. The metabolic control exerted by the tumor on TIL function was confirmed in a transgenic mouse prostate model, which exhibits similarities with human prostate cancer. These results identify a novel and dominant mechanism by which cancers induce immunosuppression in situ and suggest novel strategies for tumor immunotherapy. PMID:15824085

Boosting antitumor responses of T lymphocytes infiltrating human prostate cancers.

PubMed

Bronte, Vincenzo; Kasic, Tihana; Gri, Giorgia; Gallana, Keti; Borsellino, Giovanna; Marigo, Ilaria; Battistini, Luca; Iafrate, Massimo; Prayer-Galetti, Tommaso; Pagano, Francesco; Viola, Antonella

2005-04-18

Immunotherapy may provide valid alternative therapy for patients with hormone-refractory metastatic prostate cancer. However, if the tumor environment exerts a suppressive action on antigen-specific tumor-infiltrating lymphocytes (TIL), immunotherapy will achieve little, if any, success. In this study, we analyzed the modulation of TIL responses by the tumor environment using collagen gel matrix-supported organ cultures of human prostate carcinomas. Our results indicate that human prostatic adenocarcinomas are infiltrated by terminally differentiated cytotoxic T lymphocytes that are, however, in an unresponsive status. We demonstrate the presence of high levels of nitrotyrosines in prostatic TIL, suggesting a local production of peroxynitrites. By inhibiting the activity of arginase and nitric oxide synthase, key enzymes of L-arginine metabolism that are highly expressed in malignant but not in normal prostates, reduced tyrosine nitration and restoration of TIL responsiveness to tumor were achieved. The metabolic control exerted by the tumor on TIL function was confirmed in a transgenic mouse prostate model, which exhibits similarities with human prostate cancer. These results identify a novel and dominant mechanism by which cancers induce immunosuppression in situ and suggest novel strategies for tumor immunotherapy.

Can the Mediterranean diet prevent prostate cancer?

PubMed

Itsiopoulos, Catherine; Hodge, Allison; Kaimakamis, Mary

2009-02-01

Prostate cancer is the second most common cancer in men worldwide. Despite the global importance of this cancer, until recently little was known about risk factors apart from the well-established factors: age, family history and country of birth. The large worldwide variation in prostate cancer risk and increased risk in migrants moving from low to high risk countries provides strong support for modifiable environmental factors. We have based our review on the findings of a systematic review undertaken by an expert panel on behalf of the World Cancer Research Fund and the American Institute for Cancer Research, and new data since then, linking identified foods and nutrients with prostate cancer. Evidence indicates that foods containing lycopene, as well as selenium and foods containing it, probably protect against prostate cancer, and excess consumption of foods or supplements containing calcium are a probable cause of this cancer. The expert panel also concluded that it is unlikely that beta-carotene (whether from foods or supplements) has a substantial effect on the risk of this cancer. A recent review on environmental factors in human prostate cancer also found that there were protective effects of vitamin E, pulses, soy foods and high plasma 1,25-dihydroxyvitamin D levels. The Mediterranean diet is abundant in foods that may protect against prostate cancer and is associated with longevity and reduced cardiovascular and cancer mortality. Compared with many Western countries Greece has lower prostate cancer mortality and Greek migrant men in Australia have retained their low risk for prostate cancer. Consumption of a traditional Mediterranean diet, rich in bioactive nutrients, may confer protection to Greek migrant men, and this dietary pattern offers a palatable alternative for prevention of this disease.

Effects of dietary saw palmetto on the prostate of transgenic adenocarcinoma of the mouse prostate model (TRAMP).

PubMed

Wadsworth, Teri L; Worstell, Teresa R; Greenberg, Norman M; Roselli, Charles E

2007-05-01

Several of the proposed mechanisms for the actions of the liposterolic extract of saw palmetto (SPE) are exerted on known risk factors for prostate cancer (CaP). This study investigated whether SPE could prevent the progression of CaP in a transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Two different doses of SPE designed to deliver 50 mg/kg/day SPE and 300 mg/kg/day SPE were administered in a custom diet to TRAMP mice for 12 or 24 weeks. Body and organ weights were used to evaluate toxicity, and radioimmunoassay was used to measure plasma and tissue androgen levels to monitor effects of SPE on 5alpha reductase activity. Prostate tissues were evaluated histologically to determine the effect of treatment on tumor grade, cell proliferation, and apoptosis. Treatment with 300 mg/kg/day SPE from 4 to 24 weeks of age significantly reduced the concentration of 5alpha-dihydrotestosterone (DHT) in the prostate and resulted in a significant increase in apoptosis and significant decrease in pathological tumor grade and frank tumor incidence. Dietary supplementation with SPE may be effective in controlling CaP tumorigenesis. SPE suppression of prostatic DHT levels lends support to the hypothesis that inhibition of the enzyme 5alpha-reductase is a mechanism of action of this substance. (c) 2007 Wiley-Liss, Inc.

Definition of molecular determinants of prostate cancer cell bone extravasation.

PubMed

Barthel, Steven R; Hays, Danielle L; Yazawa, Erika M; Opperman, Matthew; Walley, Kempland C; Nimrichter, Leonardo; Burdick, Monica M; Gillard, Bryan M; Moser, Michael T; Pantel, Klaus; Foster, Barbara A; Pienta, Kenneth J; Dimitroff, Charles J

2013-01-15

Advanced prostate cancer commonly metastasizes to bone, but transit of malignant cells across the bone marrow endothelium (BMEC) remains a poorly understood step in metastasis. Prostate cancer cells roll on E-selectin(+) BMEC through E-selectin ligand-binding interactions under shear flow, and prostate cancer cells exhibit firm adhesion to BMEC via β1, β4, and αVβ3 integrins in static assays. However, whether these discrete prostate cancer cell-BMEC adhesive contacts culminate in cooperative, step-wise transendothelial migration into bone is not known. Here, we describe how metastatic prostate cancer cells breach BMEC monolayers in a step-wise fashion under physiologic hemodynamic flow. Prostate cancer cells tethered and rolled on BMEC and then firmly adhered to and traversed BMEC via sequential dependence on E-selectin ligands and β1 and αVβ3 integrins. Expression analysis in human metastatic prostate cancer tissue revealed that β1 was markedly upregulated compared with expression of other β subunits. Prostate cancer cell breaching was regulated by Rac1 and Rap1 GTPases and, notably, did not require exogenous chemokines as β1, αVβ3, Rac1, and Rap1 were constitutively active. In homing studies, prostate cancer cell trafficking to murine femurs was dependent on E-selectin ligand, β1 integrin, and Rac1. Moreover, eliminating E-selectin ligand-synthesizing α1,3 fucosyltransferases in transgenic adenoma of mouse prostate mice dramatically reduced prostate cancer incidence. These results unify the requirement for E-selectin ligands, α1,3 fucosyltransferases, β1 and αVβ3 integrins, and Rac/Rap1 GTPases in mediating prostate cancer cell homing and entry into bone and offer new insight into the role of α1,3 fucosylation in prostate cancer development.

Pharmacologic basis for the enhanced efficacy of dutasteride against prostatic cancers.

PubMed

Xu, Yi; Dalrymple, Susan L; Becker, Robyn E; Denmeade, Samuel R; Isaacs, John T

2006-07-01

Prostatic dihydrotestosterone (DHT) concentration is regulated by precursors from systemic circulation and prostatic enzymes of androgen metabolism, particularly 5alpha-reductases (i.e., SRD5A1 and SRD5A2). Therefore, the levels of expression SRD5A1 and SRD5A2 and the antiprostatic cancer growth response to finasteride, a selective SRD5A2 inhibitor, versus the dual SRD5A1 and SRD5A2 inhibitor, dutasteride, were compared. Real-time PCR and enzymatic assays were used to determine the levels of SRD5A1 and SRD5A2 in normal versus malignant rat and human prostatic tissues. Rats bearing the Dunning R-3327H rat prostate cancer and nude mice bearing LNCaP or PC-3 human prostate cancer xenografts were used as model systems. Tissue levels of testosterone and DHT were determined using liquid chromatography-mass spectrometry. Prostate cancer cells express undetectable to low levels of SRD5A2 but elevated levels of SRD5A1 activity compared with nonmalignant prostatic tissue. Daily oral treatment of rats with the SRD5A2 selective inhibitor, finasteride, reduces prostate weight and DHT content but did not inhibit R-3327H rat prostate cancer growth or DHT content in intact (i.e., noncastrated) male rats. In contrast, daily oral treatment with even a low 1 mg/kg/d dose of the dual SRD5A1 and SRD5A2 inhibitor, dutasteride, reduces both normal prostate and H tumor DHT content and weight in intact rats while elevating tissue testosterone. Daily oral treatment with finasteride significantly (P < 0.05) inhibits growth of LNCaP human prostate cancer xenografts in intact male nude mice, but this inhibition is not as great as that by equimolar oral dosing with dutasteride. This anticancer efficacy is not equivalent, however, to that produced by castration. Only combination of dutasteride and castration produces a greater tumor inhibition (P < 0.05) than castration monotherapy against androgen-responsive LNCaP cancers. In contrast, no response was induced by dutasteride in nude mice bearing

Phytochemicals from cruciferous vegetables, epigenetics, and prostate cancer prevention.

PubMed

W Watson, Gregory; M Beaver, Laura; E Williams, David; H Dashwood, Roderick; Ho, Emily

2013-10-01

Epidemiological evidence has demonstrated a reduced risk of prostate cancer associated with cruciferous vegetable intake. Follow-up studies have attributed this protective activity to the metabolic products of glucosinolates, a class of secondary metabolites produced by crucifers. The metabolic products of glucoraphanin and glucobrassicin, sulforaphane, and indole-3-carbinol respectively, have been the subject of intense investigation by cancer researchers. Sulforaphane and indole-3-carbinol inhibit prostate cancer by both blocking initiation and suppressing prostate cancer progression in vitro and in vivo. Research has largely focused on the anti-initiation and cytoprotective effects of sulforaphane and indole-3-carbinol through induction of phases I and II detoxification pathways. With regards to suppressive activity, research has focused on the ability of sulforaphane and indole-3-carbinol to antagonize cell signaling pathways known to be dysregulated in prostate cancer. Recent investigations have characterized the ability of sulforaphane and indole-3-carbinol derivatives to modulate the activity of enzymes controlling the epigenetic status of prostate cancer cells. In this review, we will summarize the well-established, "classic" non-epigenetic targets of sulforaphane and indole-3-carbinol, and highlight more recent evidence supporting these phytochemicals as epigenetic modulators for prostate cancer chemoprevention.

Comprehensive overview of prostatitis.

PubMed

Khan, Farhan Ullah; Ihsan, Awais Ullah; Khan, Hidayat Ullah; Jana, Ruby; Wazir, Junaid; Khongorzul, Puregmaa; Waqar, Muhammad; Zhou, Xiaohui

2017-10-01

Prostatitis is a common urinary tract syndrome that many doctors find problematic to treat effectively. It is the third most commonly found urinary tract disease in men after prostate cancer and Benign Prostate Hyperplasia (BPH). Prostatitis may account for 25% of all office visits made to the urological clinics complaining about the genital and urinary systems all over the world. In the present study, we classified prostatitis and comprehensively elaborated the etiology, pathogenesis, diagnosis, and treatment of acute bacterial prostatitis (category I), chronic bacterial prostatitis (category II), chronic pelvic pain syndrome (CPPS) (category III), and asymptomatic prostatitis (category IV). In addition, we also tried to get some insights about other types of prostatitis-like fungal, viral and gonococcal prostatitis. The aim of this review is to present the detail current perspective of prostatitis in a single review. To the best of our knowledge currently, there is not a single comprehensive review, which can completely elaborate this important topic in an effective way. Furthermore, this review will provide a solid platform to conduct future studies on different aspects such as risk factors, mechanism of pathogenesis, proper diagnosis, and rational treatment plans for fungal, viral, and gonococcal prostatitis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Prostatic Lesions in Odontocete Cetaceans.

PubMed

Suárez-Santana, Cristian M; Sierra, Eva; Díaz-Delgado, Josue; Zucca, Daniele; de Quirós, Yara Bernaldo; Puig-Lozano, Raquel; Câmara, Nakita; De la Fuente, Jesús; de Los Monteros, Antonio Espinosa; Rivero, Miguel; Arbelo, Manuel; Fernández, Antonio

2018-05-01

The prostate is the only accessory male genital gland described in cetaceans. Although few studies describe the gross and histologic anatomy of the prostate in cetaceans, there is no information on pathological findings involving this organ. The prostate glands of 45 cetaceans, including 8 different odontocete species ( n = 44) and 1 mysticete, were evaluated. The main pathologic diagnoses were verminous prostatitis, septic prostatitis, viral prostatitis, benign prostatic hyperplasia, and prostatitis of unknown etiology. Verminous prostatitis ( n = 12) was caused by nematodes of the genus Crassicauda, and different presentations were observed. Septic prostatitis, identified in 2 cases, both involved nematode infestation and Clostridium spp coinfection. One case of viral prostatitis was identified and was associated with morbillivirus infection. In prostatitis of unknown cause ( n = 7), varying degrees of prostatic lesions, mostly chronic inflammation, were identified. Impacts at individual levels (eg, localized disease, loss of reproductive capacity) and population levels (eg, decreased reproductive success) are plausible. Our results indicate a high occurrence of prostatic lesions in free-ranging odontocetes. For this reason, the prostate should be routinely inspected and sampled during necropsy of odontocete cetaceans.

Alendronate decreases orthotopic PC-3 prostate tumor growth and metastasis to prostate-draining lymph nodes in nude mice

PubMed Central

Tuomela, Johanna M; Valta, Maija P; Väänänen, Kalervo; Härkönen, Pirkko L

2008-01-01

Background Metastatic prostate cancer is associated with a high morbidity and mortality but the spreading mechanisms are still poorly understood. The aminobisphosphonate alendronate, used to reduce bone loss, has also been shown to inhibit the invasion and migration of prostate cancer cells in vitro. We used a modified orthotopic PC-3 nude mouse tumor model of human prostate cancer to study whether alendronate affects prostate tumor growth and metastasis. Methods PC-3 cells (5 × 105) were implanted in the prostates of nude mice and the mice were treated with alendronate (0.5 mg/kg/day in PBS, s.c.) or vehicle for 4 weeks. After sacrifice, the sizes of tumor-bearing prostates were measured and the tumors and prostate-draining regional iliac and sacral lymph nodes were excised for studies on markers of proliferation, apoptosis, angiogenesis and lymphangiogenesis, using histomorphometry and immunohistochemistry. Results Tumor occurrence in the prostate was 73% in the alendronate-treated group and 81% in the control group. Mean tumor size (218 mm3, range: 96–485 mm3, n = 11) in the alendronate-treated mice was 41% of that in the control mice (513 mm3, range: 209–1350 mm3, n = 13) (p < 0.05). In the iliac and sacral lymph nodes of alendronate-treated mice, the proportion of metastatic area was only about 10% of that in control mice (p < 0.001). Immunohistochemical staining of tumor sections showed that alendronate treatment caused a marked decrease in the number of CD34-positive endothelial cells in tumors (p < 0.001) and an increase in that of ISEL positive apoptotic cells in tumors as well as in lymph node metastases (p < 0.05) compared with those in the vehicle-treated mice. The density of m-LYVE-1-stained lymphatic capillaries was not changed. Conclusion Our results demonstrate that alendronate treatment opposes growth of orthotopic PC-3 tumors and decreases tumor metastasis to prostate-draining lymph nodes. This effect could be at least partly explained by

Prostate cancer targeting motifs: expression of αν β3, neurotensin receptor 1, prostate specific membrane antigen, and prostate stem cell antigen in human prostate cancer cell lines and xenografts.

PubMed

Taylor, Robert M; Severns, Virginia; Brown, David C; Bisoffi, Marco; Sillerud, Laurel O

2012-04-01

Membrane receptors are frequent targets of cancer therapeutic and imaging agents. However, promising in vitro results often do not translate to in vivo clinical applications. To better understand this obstacle, we measured the expression differences in receptor signatures among several human prostate cancer cell lines and xenografts as a function of tumorigenicity. Messenger RNA and protein expression levels for integrin α(ν) β(3), neurotensin receptor 1 (NTSR1), prostate specific membrane antigen (PSMA), and prostate stem cell antigen (PSCA) were measured in LNCaP, C4-2, and PC-3 human prostate cancer cell lines and in murine xenografts using quantitative reverse transcriptase polymerase chain reaction, flow cytometry, and immunohistochemistry. Stable expression patterns were observed for integrin α(ν) and PSMA in all cells and corresponding xenografts. Integrin β(3) mRNA expression was greatly reduced in C4-2 xenografts and greatly elevated in PC-3 xenografts compared with the corresponding cultured cells. NTSR1 mRNA expression was greatly elevated in LNCaP and PC-3 xenografts. PSCA mRNA expression was elevated in C4-2 xenografts when compared with C4-2 cells cultured in vitro. Furthermore, at the protein level, PSCA was re-expressed in all xenografts compared with cells in culture. The regulation of mRNA and protein expression of the cell-surface target proteins α(ν) β(3), NTSR1, PSMA, and PSCA, in prostate cancer cells with different tumorigenic potential, was influenced by factors of the microenvironment, differing between cell cultures and murine xenotransplants. Integrin α(ν) β(3), NTRS1 and PSCA mRNA expression increased with tumorigenic potential, but mRNA expression levels for these proteins do not translate directly to equivalent expression levels of membrane bound protein. Copyright © 2011 Wiley Periodicals, Inc.

Concentration of ofloxacin in canine prostate tissue and prostate fluid after intraprostatic injection of biodegradable sustained-releasing microspheres containing ofloxacin.

PubMed

Bahk, J Y; Hyun, J S; Lee, J Y; Kim, J; Cho, Y H; Lee, J H; Park, J S; Kim, M O

2000-05-01

+/- 1.4 (3 weeks) and 7.6 +/- 0.8 (4 weeks) microg./ml. The blood level in the experimental groups ranged between 0.16 to 0.59 microg./ml. The prostate fluid level ranged from 2.9 to 6.1 microg./ml. in 8 dogs. Upon pathologic examination, the microspheres were interposed between prostate stroma and their size was reduced over time. Our study indicates that there is communication between the right and left prostate lobes. Direct injection of biodegradable sustained releasing ofloxacin formula into the prostate may be a substitute for long term antibiotic medication in humans for chronic prostatitis in the future without hurting the minimal inhibitory concentration(MIC)90.

Prostate cancer - resources

MedlinePlus

Resources - prostate cancer ... The following organizations are good resources for information on prostate cancer : American Cancer Society -- www.cancer.org/cancer/prostate-cancer.html National Cancer Institute -- www.cancer.gov/ ...

The Anti-Inflammatory Effects of a Yin Zhi Huang Soup in an Experimental Autoimmune Prostatitis Rat Model

PubMed Central

Zhang, Xikui; Zhu, Weikun; Lu, Taikun; Chen, Jinchun; Zou, Qiang; Zheng, Qizhong; Chen, Junying; Jiang, Changming; Jin, Guanyu

2017-01-01

The present study aimed to investigate the therapeutic effects of the Chinese herbal medicine Yin Zhi Huang soup (YZS) in an experimental autoimmune prostatitis (EAP) rat model. In total, 48 rats were randomly divided into the following four groups (n = 12/group): saline group, pathological model group, Qianlietai group, and YZS group. We determined the average wet weight of the prostate tissue, the ratio of the wet weight of the prostate tissue to body weight, tumor necrosis factor-alpha (TNF-α) levels in the blood serum, the expression of inducible nitric oxide synthase (iNOS) in the rats' prostate tissues, and the pathological changes in the prostate tissue using light microscopy. YZS reduced the rats' prostate wet weight, the ratio of the prostate wet weight to body weight, and TNF-α levels in the blood serum and inhibited the expression of iNOS in the rats' prostate tissues (P < 0.05). Following YZS treatment, the pathological changes in the rats' prostates were improved compared with those in the model group (P < 0.05). Furthermore, YZS treatment reduced inflammatory changes in the prostate tissue. It also significantly suppressed proinflammatory cytokines, such as TNF-α, and chemokines, such as iNOS, in the rat model of EAP. PMID:29430255

The Anti-Inflammatory Effects of a Yin Zhi Huang Soup in an Experimental Autoimmune Prostatitis Rat Model.

PubMed

Deng, Longsheng; Zhang, Xikui; Zhu, Weikun; Lu, Taikun; Chen, Jinchun; Zou, Qiang; Zheng, Qizhong; Chen, Junying; Jiang, Changming; Jin, Guanyu

2017-01-01

The present study aimed to investigate the therapeutic effects of the Chinese herbal medicine Yin Zhi Huang soup (YZS) in an experimental autoimmune prostatitis (EAP) rat model. In total, 48 rats were randomly divided into the following four groups ( n = 12/group): saline group, pathological model group, Qianlietai group, and YZS group. We determined the average wet weight of the prostate tissue, the ratio of the wet weight of the prostate tissue to body weight, tumor necrosis factor-alpha (TNF- α ) levels in the blood serum, the expression of inducible nitric oxide synthase (iNOS) in the rats' prostate tissues, and the pathological changes in the prostate tissue using light microscopy. YZS reduced the rats' prostate wet weight, the ratio of the prostate wet weight to body weight, and TNF- α levels in the blood serum and inhibited the expression of iNOS in the rats' prostate tissues ( P < 0.05). Following YZS treatment, the pathological changes in the rats' prostates were improved compared with those in the model group ( P < 0.05). Furthermore, YZS treatment reduced inflammatory changes in the prostate tissue. It also significantly suppressed proinflammatory cytokines, such as TNF- α , and chemokines, such as iNOS, in the rat model of EAP.

Novel Fatty Acid Lipoxygenases in the Development of Human and Murine Prostate Cancer

DTIC Science & Technology

1999-10-01

with Dr. Matthew Breyer on a study utilizing bladder biopsy and cystectomy specimens and in situ hybridization and immunohistochemistry which...Reduced in Prostate Adenocarcinoma Scott B. Shappell,* William E. Boeglin,t prostate adenocarcinomas. (Am J Patbol 1999, Sandy J. Olson,* Susan Kasper...this novel enzyme in secretory function. 33157-33160 5. Samuelsson B. Dahlen SE, Lindgren JA, Rouzer CA, Serhan CN: Reduced expression in atrophic

Prostatitis and male infertility.

PubMed

Alshahrani, Saad; McGill, John; Agarwal, Ashok

2013-11-01

The prostate gland plays an important role in male reproduction. Inflammation of the prostate gland (prostatitis) is a common health problem affecting many young and middle aged men. Prostatitis is considered a correctable cause of male infertility, but the pathophysiology and appropriate treatment options of prostatitis in male infertility remain unclear. This literature review will focus on current data regarding prostatitis and its impact on male infertility. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Comparison of Dose Decrement from Intrafraction Motion for Prone and Supine Prostate Radiotherapy

PubMed Central

Olsen, Jeffrey; Parikh, Parag J; Watts, Michael; Noel, Camille E; Baker, Kenneth W; Santanam, Lakshmi; Michalski, Jeff M

2012-01-01

Background and Purpose Dose effects of intrafraction motion during prone prostate radiotherapy are unknown. We compared prone and supine treatment using real-time tracking data to model dose coverage. Material and Methods Electromagnetic tracking data was analyzed for 10 patients treated prone, and 15 treated supine, with IMRT for localized prostate cancer. Plans were generated using 0, 3, and 5 mm PTV expansions. Manual beam-hold interventions were applied to reposition the patient when translations exceeded a predetermined threshold. A custom software application (SWIFTER) used intrafraction tracking data acquired during beam-on to model delivered prostate dose, by applying rigid body transformations to the prostate structure contoured at simulation within the planned dose cloud. The delivered minimum prostate dose as a percentage of planned dose (Dmin%), and prostate volume covered by the prescription dose as a percentage of the planned volume (VRx%) were compared for prone and supine treatment. Results Dmin% was reduced for prone treatment for 0 (p=0.02) and 3 mm (p=0.03) PTV margins. VRx% was reduced for prone treatment only for 0 mm margins (p=0.002). No significant differences were found using 5 mm margins. Conclusions Intrafraction motion has a greater impact on target coverage for prone compared to supine prostate radiotherapy. PTV margins of 3 mm or less correlate with a significant decrease in delivered dose for prone treatment. PMID:22809590

Comparison of dose decrement from intrafraction motion for prone and supine prostate radiotherapy.

PubMed

Olsen, Jeffrey R; Parikh, Parag J; Watts, Michael; Noel, Camille E; Baker, Kenneth W; Santanam, Lakshmi; Michalski, Jeff M

2012-08-01

Dose effects of intrafraction motion during prone prostate radiotherapy are unknown. We compared prone and supine treatment using real-time tracking data to model dose coverage. Electromagnetic tracking data were analyzed for 10 patients treated prone, and 15 treated supine, with IMRT for localized prostate cancer. Plans were generated using 0 mm, 3 mm, and 5mm PTV expansions. Manual beam-hold interventions were applied to reposition the patient when translations exceeded a predetermined threshold. A custom software application (SWIFTER) used intrafraction tracking data acquired during beam-on model delivered prostate dose, by applying rigid body transformations to the prostate structure contoured at simulation within the planned dose cloud. The delivered minimum prostate dose as a percentage of planned dose (Dmin%), and prostate volume covered by the prescription dose as a percentage of the planned volume (VRx%) were compared for prone and supine treatment. Dmin% was reduced for prone treatment for 0 (p=0.02) and 3 mm (p=0.03) PTV margins. VRx% was reduced for prone treatment only for 0mm margins (p=0.002). No significant differences were found using 5 mm margins. Intrafraction motion has a greater impact on target coverage for prone compared to supine prostate radiotherapy. PTV margins of 3 mm or less correlate with a significant decrease in delivered dose for prone treatment. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Flaxseed reduces epithelial proliferation but does not affect basal cells in induced benign prostatic hyperplasia in rats.

PubMed

de Amorim Ribeiro, Ilma Cely; da Costa, Carlos Alberto Soares; da Silva, Vivian Alves Pereira; Côrrea, Lanna Beatriz Neves Silva; Boaventura, Gilson Teles; Chagas, Mauricio Alves

2017-04-01

This study aimed to quantitatively and qualitatively evaluate the effects of a flaxseed-based diet on the histoarchitecture of the prostate of normal Wistar rats and of rats with induced BPH. The study included four experimental groups of ten animals each: casein control group (CCG), who were fed a casein-based diet; flaxseed control group (FCG), who were fed a flaxseed-based diet; hyperplasia-induced casein group (HICG), who were fed a casein-based diet; and hyperplasia-induced flaxseed group (HIFG), who were fed a flaxseed-based diet. Hyperplasia was induced by the subcutaneous implantation of silicone pellets containing testosterone propionate. After 20 weeks, the rats were euthanized and their prostate fixed in buffered formalin. Tissue sections were stained with HE, picrosirius red and immunostained for nuclear antigen p63. Histomorphometric analysis evaluated the epithelial thickness, epithelial area, individual luminal area, and total area of prostatic alveoli. The mean epithelial thickness obtained for HIFG and HICG was 16.52 ± 1.65 and 20.58 ± 2.86 µm, respectively. The mean epithelial thickness in HICG was greater than that in the other groups tested. HIFG had a smaller epithelial thickness and lower percentage of papillary projections in the prostatic alveoli. No significant difference was observed between CCG and FCG. The total area and mean alveolar area showed no significant differences between the groups. The number of cells immunostained for p63 was not significantly different between the groups evaluated. These results suggest that flaxseed has a protective effect on the prostate epithelium in BPH-induced animals.

14-3-3 Proteins Modulate the ETS Transcription Factor ETV1 in Prostate Cancer

PubMed Central

Oh, Sangphil; Shin, Sook; Lightfoot, Stan A.; Janknecht, Ralf

2013-01-01

Overexpression of the ETS-related transcription factor ETV1 can initiate neoplastic transformation of the prostate. ETV1 activity is highly regulated by phosphorylation, but the underlying mechanisms are unknown. Here we report that all 14-3-3 proteins, with the exception of the tumor suppressor 14-3-3σ, can bind to ETV1 in a condition manner dictated by its prominent phosphorylation site S216. All non-σ 14-3-3 proteins synergized with ETV1 to activate transcription of its target genes MMP-1 and MMP-7, which regulate extracellular matrix in the prostate tumor microenvironment. S216 mutation or 14-3-3τ downregulation was sufficient to reduce ETV1 protein levels in prostate cancer cells, indicating that non-σ 14-3-3 proteins protect ETV1 from degradation. Notably, S216 mutation also decreased ETV1-dependent migration and invasion in benign prostate cells. Downregulation of 14-3-3τ reduced prostate cancer cell invasion and growth in the same manner as ETV1 attenuation. Lastly, we showed that 14-3-3τ and 14-3-3ε were overexpressed in human prostate tumors. Taken together, our results demonstrated that non-σ 14-3-3 proteins are important modulators of ETV1 function that promote prostate tumorigenesis. PMID:23774214

Role of PROPELLER-DWI of the prostate in reducing distortion and artefact from total hip replacement metalwork.

PubMed

Czarniecki, Marcin; Caglic, Iztok; Grist, James T; Gill, Andrew B; Lorenc, Kamil; Slough, Rhys A; Priest, Andrew N; Barrett, Tristan

2018-05-01

To compare image quality, artefact, and distortion in standard echo-planar imaging (EPI) with periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) for prostate magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) in patients with previous total hip replacement (THR). 21 male subjects with a clinical suspicion for, or known prostate cancer and previous THR were scanned at 1.5 T using a phased-array body coil. DWI was obtained using single-shot EPI and PROPELLER techniques using fat saturation (PROPELLER-DWI-FS), and without (PROPELLER-DWI-NFS). Image quality (the overall impression of diagnostic quality) was compared to T 2 -weighted (T2WI) imaging using a 5-point Likert scale, with diffusion sequences additionally scored for artefact and distortion according to a 4-point scale, with artefact defined as the amount of prostate affected and distortion as the degree of warping of the organ. The T2W and DW image volumes were compared to produce quantitative distortion maps. A two-sample Wilcoxon test compared the qualitative scores, with inter-reader variability calculated using Cohen's kappa. 21 patients were included in the study, with an average age of 70.4 years and PSA 9.2 ng/ml. Hip metalwork was present bilaterally in 3 patients, left-sided in 9, and right-sided in 9. PROPELLER-DWI-FS significantly improved image quality (p < 0.01) and reduced distortion (p < 0.01) when compared to standard EP-DWI. Artefact was not shown to be significantly improved. The last 5 patients in the study were additionally imaged with PROPELLER-DWI-NFS, which resulted in a significant reduction in artefact compared to EP-DWI (p < 0.05). Quantitative distortion was significantly lower compared to EP-DWI for both PROPELLER with fat saturation (p < 0.01) and without fat saturation (p < 0.01). PROPELLER-DWI demonstrates better image quality and decreases both artefact and distortion compared to conventional echo

High animal fat intake enhances prostate cancer progression and reduces glutathione peroxidase 3 expression in early stages of TRAMP mice.

PubMed

Chang, Seo-Na; Han, Juhee; Abdelkader, Tamer Said; Kim, Tae-Hyoun; Lee, Ji Min; Song, Juha; Kim, Kyung-Sul; Park, Jong-Hwan; Park, Jae-Hak

2014-09-01

Prostate cancer is the most frequently diagnosed cancer in Western men, and more men have been diagnosed at younger ages in recent years. A high-fat Western-style diet is a known risk factor for prostate cancer and increases oxidative stress. We evaluated the association between dietary animal fat and expression of antioxidant enzymes, particularly glutathione peroxidase 3 (GPx3), in the early stages of transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. Six-week-old male nontransgenic and TRAMP mice were placed on high animal fat (45% Kcal fat) or control (10% Kcal fat) diets and sacrificed after 5 or 10 weeks. The histopathological score increased with age and high-fat diet consumption. The histopathological scores in dorsal and lateral lobes increased in the 10-week high-fat diet group (6.2±0.2 and 6.2±0.4, respectively) versus the 10-week control diet group (5.3±0.3 and 5.2±0.2, respectively). GPx3 decreased both at the mRNA and protein levels in mouse prostate. GPx3 mRNA expression decreased (∼36.27% and ∼23.91%, respectively) in the anterior and dorsolateral prostate of TRAMP mice fed a high-fat diet compared to TRAMP mice fed a control diet. Cholesterol treatment increased PC-3 human prostate cancer cell proliferation, decreased GPx3 mRNA and protein levels, and increased H2 O2 levels in culture medium. Moreover, increasing GPx3 mRNA expression by troglitazone in PC-3 cells decreased cell proliferation and lowered H2 O2 levels. Dietary fat enhances prostate cancer progression, possibly by suppressing GPx3 expression and increasing proliferation of prostate intraepithelial neoplasia (PIN) epithelial cells. © 2014 Wiley Periodicals, Inc.

Seminal epithelium in prostate biopsy can mimic malignant and premalignant prostatic lesions.

PubMed

Arista-Nasr, J; Trolle-Silva, A; Aguilar-Ayala, E; Martínez-Benítez, B

2016-01-01

In most prostate biopsies, the seminal epithelium is easily recognised because it meets characteristic histological criteria. However, some biopsies can mimic malignant or premalignant prostatic lesions. The aims of this study were to analyse the histological appearance of the biopsies that mimic adenocarcinomas or preneoplastic prostatic lesions, discuss the differential diagnosis and determine the frequency of seminal epithelia in prostate biopsies. We consecutively reviewed 500 prostate puncture biopsies obtained using the sextant method and selected those cases in which we observed seminal vesicle or ejaculatory duct epithelium. In the biopsies in which the seminal epithelium resembled malignant or premalignant lesions, immunohistochemical studies were conducted that included prostate-specific antigen and MUC6. The most important clinical data were recorded. Thirty-six (7.2%) biopsies showed seminal epithelium, and 7 of them (1.4%) resembled various prostate lesions, including high-grade prostatic intraepithelial neoplasia, atypical acinar proliferations, adenocarcinomas with papillary patterns and poorly differentiated carcinoma. The seminal epithelium resembled prostate lesions when the lipofuscin deposit, the perinuclear vacuoles or the nuclear pseudoinclusions were inconspicuous or missing. Five of the 7 biopsies showed mild to moderate cellular atypia with small and hyperchromatic nuclei, and only 2 showed cellular pleomorphism. The patients were alive and asymptomatic after an average of 6 years of progression. The seminal epithelium resembles prostatic intraepithelial neoplasia, atypical acinar proliferations and various types of prostatic adenocarcinomas in approximately 1.4% of prostate biopsies. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

STEAP: A prostate-specific cell-surface antigen highly expressed in human prostate tumors

PubMed Central

Hubert, Rene S.; Vivanco, Igor; Chen, Emily; Rastegar, Shiva; Leong, Kahan; Mitchell, Steve C.; Madraswala, Rashida; Zhou, Yanhong; Kuo, James; Raitano, Arthur B.; Jakobovits, Aya; Saffran, Douglas C.; Afar, Daniel E. H.

1999-01-01

In search of novel genes expressed in metastatic prostate cancer, we subtracted cDNA isolated from benign prostatic hypertrophic tissue from cDNA isolated from a prostate cancer xenograft model that mimics advanced disease. One novel gene that is highly expressed in advanced prostate cancer encodes a 339-amino acid protein with six potential membrane-spanning regions flanked by hydrophilic amino- and carboxyl-terminal domains. This structure suggests a potential function as a channel or transporter protein. This gene, named STEAP for six-transmembrane epithelial antigen of the prostate, is expressed predominantly in human prostate tissue and is up-regulated in multiple cancer cell lines, including prostate, bladder, colon, ovarian, and Ewing sarcoma. Immunohistochemical analysis of clinical specimens demonstrates significant STEAP expression at the cell–cell junctions of the secretory epithelium of prostate and prostate cancer cells. Little to no staining was detected at the plasma membranes of normal, nonprostate human tissues, except for bladder tissue, which expressed low levels of STEAP at the cell membrane. Protein analysis located STEAP at the cell surface of prostate-cancer cell lines. Our results support STEAP as a cell-surface tumor-antigen target for prostate cancer therapy and diagnostic imaging. PMID:10588738

Inhibition of prostate smooth muscle contraction and prostate stromal cell growth by the inhibitors of Rac, NSC23766 and EHT1864.

PubMed

Wang, Y; Kunit, T; Ciotkowska, A; Rutz, B; Schreiber, A; Strittmatter, F; Waidelich, R; Liu, C; Stief, C G; Gratzke, C; Hennenberg, M

2015-06-01

Medical therapy of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) targets smooth muscle contraction in the prostate, or prostate growth. However, current therapeutic options are insufficient. Here, we investigated the role of Rac in the control of smooth muscle tone in human prostates and growth of prostate stromal cells. Experiments were performed using human prostate tissues from radical prostatectomy and cultured stromal cells (WPMY-1). Expression of Rac was examined by Western blot and fluorescence staining. Effects of Rac inhibitors (NSC23766 and EHT1864) on contractility were assessed in the organ bath. The effects of Rac inhibitors were assessed by pull-down, cytotoxicity using a cell counting kit, cytoskeletal organization by phalloidin staining and cell growth using an 5-ethynyl-2'-deoxyuridine assay. Expression of Rac1-3 was observed in prostate samples from each patient. Immunoreactivity for Rac1-3 was observed in the stroma, where it colocalized with the smooth muscle marker, calponin. NSC23766 and EHT1864 significantly reduced contractions of prostate strips induced by noradrenaline, phenylephrine or electrical field stimulation. NSC23766 and EHT1864 inhibited Rac activity in WPMY-1 cells. Survival of WPMY-1 cells ranged between 64 and 81% after incubation with NSC23766 (50 or 100 μM) or EHT1864 (25 μM) for 24 h. NSC23766 and EHT1864 induced cytoskeletal disorganization in WPMY-1 cells. Both inhibitors impaired the growth of WPMY-1 cells. Rac may be a link connecting the control of prostate smooth muscle tone with proliferation of smooth muscle cells. Improvements in LUTS suggestive of BPH by Rac inhibitors appears possible. © 2015 The British Pharmacological Society.

"Textural analysis of multiparametric MRI detects transition zone prostate cancer".

PubMed

Sidhu, Harbir S; Benigno, Salvatore; Ganeshan, Balaji; Dikaios, Nikos; Johnston, Edward W; Allen, Clare; Kirkham, Alex; Groves, Ashley M; Ahmed, Hashim U; Emberton, Mark; Taylor, Stuart A; Halligan, Steve; Punwani, Shonit

2017-06-01

To evaluate multiparametric-MRI (mpMRI) derived histogram textural-analysis parameters for detection of transition zone (TZ) prostatic tumour. Sixty-seven consecutive men with suspected prostate cancer underwent 1.5T mpMRI prior to template-mapping-biopsy (TPM). Twenty-six men had 'significant' TZ tumour. Two radiologists in consensus matched TPM to the single axial slice best depicting tumour, or largest TZ diameter for those with benign histology, to define single-slice whole TZ-regions-of-interest (ROIs). Textural-parameter differences between single-slice whole TZ-ROI containing significant tumour versus benign/insignificant tumour were analysed using Mann Whitney U test. Diagnostic accuracy was assessed by receiver operating characteristic area under curve (ROC-AUC) analysis cross-validated with leave-one-out (LOO) analysis. ADC kurtosis was significantly lower (p < 0.001) in TZ containing significant tumour with ROC-AUC 0.80 (LOO-AUC 0.78); the difference became non-significant following exclusion of significant tumour from single-slice whole TZ-ROI (p = 0.23). T1-entropy was significantly lower (p = 0.004) in TZ containing significant tumour with ROC-AUC 0.70 (LOO-AUC 0.66) and was unaffected by excluding significant tumour from TZ-ROI (p = 0.004). Combining these parameters yielded ROC-AUC 0.86 (LOO-AUC 0.83). Textural features of the whole prostate TZ can discriminate significant prostatic cancer through reduced kurtosis of the ADC-histogram where significant tumour is included in TZ-ROI and reduced T1 entropy independent of tumour inclusion. • MR textural features of prostate transition zone may discriminate significant prostatic cancer. • Transition zone (TZ) containing significant tumour demonstrates a less peaked ADC histogram. • TZ containing significant tumour reveals higher post-contrast T1-weighted homogeneity. • The utility of MR texture analysis in prostate cancer merits further investigation.

Prostate Mechanical Imaging: A New Method For Prostate Assessment

PubMed Central

Weiss, Robert E; Egorov, Vladimir; Ayrapetyan, Suren; Sarvazyan, Noune; Sarvazyan, Armen

2008-01-01

Objectives To evaluate the ability of Prostate Mechanical Imaging (PMI) technology to provide an objective and reproducible image and to assess the prostate nodularity. Methods The PMI device developed by Artann Laboratories was evaluated in a pilot clinical study. For the 168 patients (ages 44 to 94) presented to an urologist for prostate evaluation, PMI-produced images and assessment of prostate size, shape, consistency/hardness, mobility, nodularity, and was compared with digital rectal examination (DRE) findings. The PMI and DRE results were further tested for correlation against a transrectal ultrasound of the prostate (TRUS) guided biopsy for a sub-group of 21 patients with an elevated PSA level. Results In 84% of the cases the PMI device was able to reconstruct 3-D and 2-D cross-sectional images of the prostate. The PMI System and DRE pre-tests were able to determine malignant nodules in 10 and 6 patients, respectively, of the 13 patients with biopsy-confirmed malignant inclusions. The PMI System findings were consistent with all 8 biopsy negative cases, while the DRE had 1 abnormal reading for this group. The correlation between PMI and DRE detection of palpable nodularity was 81%, as indicated by the area under the receiver operating characteristic (ROC) curve. Estimates of the prostate size provided by PMI and DRE were found to be statistically significantly correlated. Conclusions The PMI has the potential to enable a physician to obtain, examine and store a three dimensional image of the prostate based on mechanical and geometrical characteristics of the gland and its internal structures. PMID:18342178

Analysis of costs of transrectal prostate biopsy.

PubMed

Fandella, Andrea

2011-01-01

Literature reports mortality and morbidity data from prostatic carcinoma which permit a better use of some routine diagnostic tools such as transrectal ultrasound-guided biopsy. The aim of this work is to quantify the overall cost of transrectal ultrasound biopsy of the prostate (TRUSB) and to assess the economic impact of current procedures for diagnosing prostatic carcinoma. The total cost of TRUSB was calculated with reference to 247 procedures performed in 2008. The following cost factors were evaluated: personnel, materials, maintenance/depreciation of the equipment, energy consumption, and hospital overheads. A literature review was also carried out to check if our extrapolated costs corresponded to those of other authors worldwide, and to consider them in the wider framework of the economic effectiveness of strategies for early diagnosis of cancer of the prostate. The overall cost of TRUSB (8 samples) was EUR 249,000, obtained by adding together the costs of: personnel (EUR 160,000); materials (EUR 59,000); equipment maintenance and depreciation (EUR 12,400); energy consumption (EUR0,1); hospital overheads (EUR 17,500). With extended or saturation biopsies the cost increases for the more time needed by pathologists and can be calculated as EUR 300,000. The literature review points out TRUSB as an invasive tool for diagnosing prostatic carcinoma, clinically and economically controversial. Post-mortem data report the presence of cancer cells in the prostate of 50% of 70-year-old men, while extrapolations calculate a morbidity rate from prostatic carcinoma in 9.5% of 50-year-old men. It is therefore obvious that randomized prostatic biopsies, methods apart, have a good probability of being positive. This probability varies with the patient's age, the level of prostate specific antigen (PSA), the density of PSA/cm3 of prostate volume (PSAD), and the detection by digital exploration and/or positive transrectal ultrasound. CONCLUSIONS. Despite the severe

Coffee and tea consumption in relation to prostate cancer prognosis

PubMed Central

Geybels, Milan S.; Neuhouser, Marian L.; Wright, Jonathan L.; Stott-Miller, Marni; Stanford, Janet L.

2013-01-01

Background Bioactive compounds found in coffee and tea may delay the progression of prostate cancer. Methods We investigated associations of pre-diagnostic coffee and tea consumption with risk of prostate cancer recurrence/progression. Study participants were men diagnosed with prostate cancer in 2002–2005 in King County, Washington, USA. We assessed the usual pattern of coffee and tea consumption two years before diagnosis date. Prostate cancer outcome events were identified using a detailed follow-up survey. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results The analysis of coffee intake in relation to prostate cancer recurrence/progression included 630 patients with a median follow-up of 6.4 years, during which 140 prostate cancer recurrence/progression events were recorded. Approximately 61% of patients consumed at least one cup of coffee per day. Coffee consumption was associated with a reduced risk of prostate cancer recurrence/progression; the adjusted HR for ≥4 cups/day versus ≤1 cup/week was 0.41 (95% CI: 0.20, 0.81; P for trend = 0.01). Approximately 14% of patients consumed one or more cups of tea per day, and tea consumption was unrelated to prostate cancer recurrence/progression. Conclusion Results indicate that pre-diagnostic coffee consumption is associated with a lower risk of prostate cancer recurrence/progression. This finding will require replication in larger studies. PMID:23907772

Can prostatic arterial embolisation (PAE) reduce the volume of the peripheral zone? MRI evaluation of zonal anatomy and infarction after PAE.

PubMed

Lin, Yen-Ting; Amouyal, Grégory; Correas, Jean-Michel; Pereira, Héléna; Pellerin, Olivier; Del Giudice, Costantino; Déan, Carole; Thiounn, Nicolas; Sapoval, Marc

2016-10-01

To assess the impact of prostatic arterial embolisation (PAE) on various prostate gland anatomical zones. We retrospectively reviewed paired MRI scans obtained before and after PAE for 25 patients and evaluated changes in volumes of the median lobe (ML), central gland (CG), peripheral zone (PZ) and whole prostate gland (WPV) following PAE. We used manual segmentation to calculate volume on axial view T2-weighted images for ML, CG and WPV. We calculated PZ volume by subtracting CG volume from WPV. Enhanced phase on dynamic contrasted-enhanced MRI was used to evaluate the infarction areas after PAE. Clinical results of International Prostate Symptom Score and International Index of Erectile Function questionnaires and the urodynamic study were evaluated before and after PAE. Significant reductions in volume were observed after PAE for ML (26.2 % decrease), CG (18.8 %), PZ (16.4 %) and WPV (19.1 %; p < 0.001 for all these volumes). Patients with clinical failure had smaller volume reductions for WPV, ML and CG (all p < 0.05). Patients with significant CG infarction after PAE displayed larger WPV, ML and CG volume reductions (all p < 0.01). PAE can significantly decrease WPV, ML, CG and PZ volumes, and poor clinical outcomes are associated with smaller volume reductions. • The MRI segmentation method provides detailed comparisons of prostate volume change. • Prostatic arterial embolisation (PAE) decreased central gland and peripheral zone volumes. • Prostates with infarction after PAE showed larger decreases in volume. • A larger decrease in prostate volume is associated with clinical success.

TCDD Inhibition of Canonical Wnt Signaling Disrupts Prostatic Bud Formation in Mouse Urogenital Sinus

PubMed Central

Peterson, Richard E.

2013-01-01

In mice, in utero exposure to 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) reduces the number of dorsolateral prostatic buds resulting in a smaller dorsolateral prostate and prevents formation of ventral buds culminating in ventral prostate agenesis. The genes and signaling pathways affected by TCDD that are responsible for disrupting prostate development are largely unknown. Here we show that treatment of urogenital sinus (UGS) organ cultures with known inhibitors of canonical Wnt signaling also inhibits prostatic bud formation. In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of TCDD on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD. Thus, the TCDD-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and Rspo3) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway. This study focuses on determining whether treatment of TCDD-exposed UGS organ cultures with RSPO2 and/or RSPO3 is capable of rescuing the inhibitory effects of TCDD on canonical Wnt signaling and prostatic bud formation. We discovered that each RSPO alone or in combination partially rescues TCDD inhibition of both canonical Wnt signaling and prostatic bud formation. PMID:23429912

TCDD inhibition of canonical Wnt signaling disrupts prostatic bud formation in mouse urogenital sinus.

PubMed

Branam, Amanda M; Davis, Nicole M; Moore, Robert W; Schneider, Andrew J; Vezina, Chad M; Peterson, Richard E

2013-05-01

In mice, in utero exposure to 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) reduces the number of dorsolateral prostatic buds resulting in a smaller dorsolateral prostate and prevents formation of ventral buds culminating in ventral prostate agenesis. The genes and signaling pathways affected by TCDD that are responsible for disrupting prostate development are largely unknown. Here we show that treatment of urogenital sinus (UGS) organ cultures with known inhibitors of canonical Wnt signaling also inhibits prostatic bud formation. In support of the hypothesis that TCDD decreases canonical Wnt signaling, we identify inhibitory effects of TCDD on multiple components of the canonical Wnt signaling pathway in the UGS that temporally coincide with the inhibitory effect of TCDD on prostatic bud formation: (1) expression of R-spondins (Rspo2 and Rspo3) that promote canonical Wnt signaling is reduced; (2) expression of Lef1, Tcf1, and Wif1, established canonical Wnt target genes, is decreased; (3) expression of Lgr5, a RSPO receptor that activates canonical Wnt signaling, is reduced; and (4) expression of Dickkopfs (Dkks), inhibitors of canonical Wnt signaling, is not increased by TCDD. Thus, the TCDD-induced reduction in canonical Wnt signaling is associated with a decrease in activators (Rspo2 and Rspo3) rather than an increase in inhibitors (Dkk1 and Dkk2) of the pathway. This study focuses on determining whether treatment of TCDD-exposed UGS organ cultures with RSPO2 and/or RSPO3 is capable of rescuing the inhibitory effects of TCDD on canonical Wnt signaling and prostatic bud formation. We discovered that each RSPO alone or in combination partially rescues TCDD inhibition of both canonical Wnt signaling and prostatic bud formation.

Saw palmetto supplement use and prostate cancer risk.

PubMed

Bonnar-Pizzorno, Raven M; Littman, Alyson J; Kestin, Mark; White, Emily

2006-01-01

Saw palmetto is an herb used to treat the symptoms of benign prostatic hyperplasia. In vitro studies have found that saw palmetto inhibits growth of prostatic cancer cells and may induce apoptosis. To evaluate whether saw palmetto supplements are associated with a reduced risk of prostate cancer, we conducted a prospective cohort study of 35,171 men aged 50-76 yr in western Washington state. Subjects completed questionnaires between 2000 and 2002 on frequency of use of saw palmetto supplements and saw palmetto-containing multivitamins over the previous 10 yr in addition to other information on supplement intake, medical history, and demographics. Men were followed through December 2003 (mean of 2.3 yr of follow-up) via the western Washington Surveillance, Epidemiology, and End Results cancer registry, during which time 580 developed prostate cancer. Ten percent of the cohort used saw palmetto at least once per week for a year in the 10 yr before baseline. No association was found between this level of use of saw palmetto and risk of prostate cancer development [hazard ratio (HR) = 0.95; 95% confidence interval = 0.74-1.23] or with increasing frequency or duration of use. In this free-living population, use of commercial saw palmetto, which varies widely in dose and constituent ratios, was not associated with prostate cancer risk.

Influence of the neural microenvironment on prostate cancer

PubMed Central

Coarfa, Christian; Florentin, Diego; Putluri, NagiReddy; Ding, Yi; Au, Jason; He, Dandan; Ragheb, Ahmed; Frolov, Anna; Michailidis, George; Lee, MinJae; Kadmon, Dov; Miles, Brian; Smith, Christopher; Ittmann, Michael; Rowley, David; Sreekumar, Arun; Creighton, Chad J.

2017-01-01

Background Nerves are key factors in prostate cancer (PCa), but the functional role of innervation in prostate cancer is poorly understood. PCa induced neurogenesis and perineural invasion (PNI), are associated with aggressive disease. Method We denervated rodent prostates chemically and physically, before orthotopically implanting cancer cells. We also performed a human neoadjuvant clinical trial using botulinum toxin type A (Botox) and saline in the same patient, before prostatectomy. Result Bilateral denervation resulted in reduced tumor incidence and size in mice. Botox treatment in humans resulted in increased apoptosis of cancer cells in the Botox treated side. A similar denervation gene array profile was identified in tumors arising in denervated rodent prostates, in spinal cord injury patients and in the Botox treated side of patients. Denervation induced exhibited a signature gene profile, indicating translation and bioenergetic shutdown. Nerves also regulate basic cellular functions of non‐neoplastic epithelial cells. Conclusion Nerves play a role in the homeostasis of normal epithelial tissues and are involved in prostate cancer tumor survival. This study confirms that interactions between human cancer and nerves are essential to disease progression. This work may make a major impact in general cancer treatment strategies, as nerve/cancer interactions are likely important in other cancers as well. Targeting the neural microenvironment may represent a therapeutic approach for the treatment of human prostate cancer. PMID:29131367

Prostate cancer, benign prostatic hyperplasia and physical activity in Shanghai, China.

PubMed

Lacey, J V; Deng, J; Dosemeci, M; Gao, Y T; Mostofi, F K; Sesterhenn, I A; Xie, T; Hsing, A W

2001-04-01

Studies suggest that increased levels of physical activity might decrease the risk of prostate cancer. We ascertained lifetime measures of activity in a population-based case-control study of prostate cancer in Shanghai, China to investigate physical activity in a population where the incidence of prostate cancer is low but rising. In all, 238 men with prostate cancer, diagnosed 1993-1995, were identified through a rapid reporting system. A second group of 206 men with benign prostatic hyperplasia (BPH) was matched to prostate cancer cases, and 471 age-matched and population-based controls were identified from urban Shanghai. Through personal interviews, we ascertained all daily, occupational, and recreational activities at ages 20-29, ages 40-49, and in 1988 to generate hours spent sleeping, sitting, in moderate activity, and in vigorous activity. Time spent per week in different activities was converted to metabolic equivalents (MET-h) and energy expended. Time spent in, MET-h of, and energy expended in physical activities were not consistently related to either prostate cancer or BPH when compared to controls. Few men reported regular vigorous activity. Occupational activity, based on an energy expenditure index using job titles, was suggestively associated with a decreased risk of BPH, but not associated with prostate cancer. Associations did not vary according to age or stage of prostate cancer at diagnosis. Our results, based on regular physical activity, occupational activity, hours in activities, MET-h, and energy expended, did not support a protective role of physical activity in prostate cancer or BPH for men in a low-risk population.

Null effect of dietary restriction on prostate carcinogenesis in the Wistar-Unilever rat.

PubMed

McCormick, David L; Johnson, William D; Haryu, Todd M; Bosland, Maarten C; Lubet, Ronald A; Steele, Vernon E

2007-01-01

Chronic dietary restriction inhibits carcinogenesis in several sites in laboratory animals. To determine the effects of dietary restriction on prostate carcinogenesis, prostate cancers were induced in male Wistar-Unilever rats by a sequential regimen of cyproterone acetate (50 mg/day; 21 days); testosterone propionate (100 mg/kg/day; 3 days); N-methyl-N-nitrosourea [MNU; 30 mg/kg; single dose]; and testosterone (subcutaneous implants of 2 pellets containing 40 mg each). Dietary restriction (0% [ad libitum control], 15%, or 30%) was initiated 2 wk post-MNU, and continued until study termination at 12 mo. Dietary restriction induced a rapid suppression of body weight gain but conferred no protection against prostate carcinogenesis. 74% of carcinogen-treated ad libitum controls developed accessory sex gland cancers, versus cancer incidences of 64% and 72% in groups restricted by 15% and 30%, respectively. Similarly, 44% of dietary controls developed cancers limited to the dorsolateral/prostate, versus incidences of 45% and 53% in groups restricted by 15% and 30%. The results of the present study do not support the hypothesis that prostate carcinogenesis can be prevented by reducing caloric intake. Reducing mean body weight by up to 25% through chronic dietary restriction has no effect on the induction of prostate cancers in the Wistar-Unilever rat model.

Prostate brachytherapy - discharge

MedlinePlus

... chap 84. Read More Prostate brachytherapy Prostate cancer Prostate-specific antigen (PSA) blood test Radical prostatectomy Review Date 2/21/2017 Updated by: Jennifer Sobol, DO, Urologist with the Michigan ... Cancer Browse the Encyclopedia A.D.A.M., ...

Enlarged Prostate (BPH)

MedlinePlus

The prostate is a gland in men. It helps make semen, the fluid that contains sperm. The prostate surrounds the tube that carries urine out of the body. As men age, their prostate grows bigger. If it gets ...

Androgen Deprivation Accelerates the Prostatic Urethra Wound Healing After Thulium Laser Resection of the Prostate by Promoting Re-Epithelialization and Regulating the Macrophage Polarization.

PubMed

Wang, Xing-Jie; Zhuo, Jian; Luo, Guang-Heng; Zhu, Yi-Ping; Yu, Dian-Jun; Zhao, Rui-Zhe; Jiang, Chen-Yi; Shi, Yun-Feng; Li, Hao; Chen, Lei; Hao, Kui-Yuan; Han, Xia; Zhao, Sheng; Bei, Xiao-Yu; Jing, Yi-Feng; Xia, Shu-Jie

2017-05-01

Complications after a thulium laser resection of the prostate (TmLRP) are related to re-epithelialization of the prostatic urethra. Since prostate growth and development are induced by androgen, the aim of this study was to determine the role and explore the mechanism of androgen in wound healing of the prostatic urethra. Beagles that received TmLRPs were randomly distributed into a castration group, a testosterone undecanoate (TU) group, and a control group. The prostate wound was assessed once a week using a cystoscope. Histological analysis was then carried out to study the re-epithelialization of the prostatic urethra in each group. The inflammatory response in the wound tissue and urine was also investigated. The healing of the prostatic urethra after a TmLRP was more rapid in the castration group and slower in the TU group than that in the control group. Castration accelerated re-epithelialization by promoting basal cell proliferation in the wound surface and beneath the wound and by accelerating the differentiation of basal cells into urothelial cells. Castration reduced the duration of the inflammatory phase and induced the conversion of M1 macrophages to M2 macrophages, thus accelerating the maturation of the wound. By contrast, androgen supplementation enhanced the inflammatory response and prolonged the inflammatory phase. Moreover, the anti-inflammatory phase was delayed and weakened. Androgen deprivation promotes re-epithelialization of the wound, regulates the inflammatory response, and accelerates wound healing of the prostatic urethra after a TmLRP. Prostate 77:708-717, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

[Prostatic calculi: silent stones].

PubMed

Köseoğlu, H; Aslan, G; Sen, B H; Tuna, B; Yörükoğlu, K

2010-06-01

Prostate stones are frequently encountered during transurethral resection of the prostate in urology practice. We aimed to demonstrate the physical and chemical properties of prostate stones. We also aimed to determine possible relationship between inflammation of prostate gland and prostate stones. The consecutive patients (excluding subjects with PSA>or=4ng/ml and urolithiasis), who underwent TURP operation and who were observed to have prostatic calculi during TURP, were included in the study. The prostatic stones obtained from each patient during TURP were analysed for chemical composition and observed under electron microscopy (SEM) for structure and surface morphology. The pathological specimens were assessed by the uropathologist for the final diagnosis and existence and degree of inflammation. Five patients were included in the study. From each patient at least three (range 3-8) samples of stones (diameter varying from 1mm up to 5mm) were obtained. The stones were made of mixed composition of calcium phosphate and calcium carbonate. The stones were found to have lobular surface made up of small spheres under SEM. Histopathological examination of the TURP specimens revealed being prostatic hyperplasia accompanied with inflammation of mild to severe degree. Prostatic stones are concentrically precipitated calcium stones within the prostatic ductuli with granular grape like morphology. Histopathological inflammation seems to be associated with these prostatic calculi.

Effects of imatinib mesylate on the spontaneous activity generated by the guinea-pig prostate.

PubMed

Lam, Michelle; Dey, Anupa; Lang, Richard J; Exintaris, Betty

2013-08-01

What's known on the subject? and what does the study add?: Several studies have examined the functional role of tyrosine kinase receptors in the generation of spontaneous activity in various segments of the gastrointestinal and urogenital tracts through the application of its inhibitor, imatinib mesylate (Glivec®), but results are fairly inconsistent. This is the first study detailing the effects of imatinib mesylate on the spontaneous activity in the young and ageing prostate gland. As spontaneous electrical activity underlies the spontaneous rhythmic prostatic contractions that occur at rest, elucidating the mechanisms involved in the regulation of the spontaneous electrical activity and the resultant phasic contractions could conceivably lead to the identification of better targets and the development of more specific therapeutic agents to treat prostate conditions. To investigate the effect of imatinib mesylate, a tyrosine kinase receptor inhibitor, in the generation of spontaneous electrical and contractile activity in the young and ageing guinea-pig prostate. Standard tension and intracellular recording were used to measure spontaneous contractions and slow waves, respectively from the guinea-pig prostate at varying concentrations of imatinib mesylate (1-50 μm). Imatinib mesylate (1-10 μm), did not significantly affect slow waves recorded in the prostate of both age groups but at 50 μm, the amplitude of slow waves from the ageing guinea-pig prostate was significantly reduced (P < 0.05, n = 5). In contrast, the amplitude of contractions across all concentrations in the young guinea-pig prostate was reduced to between 35% and 41% of control, while the frequency was reduced to 15.7% at 1 μm (n = 7), 49.8% at 5 μm (n = 10), 46.2% at 10 μm (n = 7) and 53.1% at 50 μm (n = 5). Similarly, imatinib mesylate attenuated the amplitude and slowed the frequency of contractions in ageing guinea-pigs to 5.15% and 3.3% at 1 μm (n = 6); 21.1% and 20.8% at 5 μm (n = 8

Oxytocin: its role in benign prostatic hyperplasia via the ERK pathway.

PubMed

Xu, Huan; Fu, Shi; Chen, Yanbo; Chen, Qi; Gu, Meng; Liu, Chong; Qiao, Zhiguang; Zhou, Juan; Wang, Zhong

2017-04-01

The aim of the present study was to evaluate oxytocin and benign prostatic hyperplasia (BPH), and study the cell signalling mechanism. Investigation was performed in patients about the correlation between oxytocin level and BPH. Mice were injected with oxytocin or oxytocin antagonist for 2 weeks and the prostate morphology was studied after their sacrifice. Furthermore, in vitro experiments were performed to evaluate the oxytocin effect through the MEK/ERK/RSK pathway. Oxytocin was significantly elevated in the serum and prostate tissue of patients with BPH, and a positive correlation with prostate volume indicated. In the animal experiments, prostate enlargement was observed in the oxytocin-treated group, whereas oxytocin antagonist reduced prostate hyperplasia. The in vitro study confirmed this result and also revealed activation of the MEK/ERK/RSK pathway. Oxytocin is highly expressed in the serum and prostate tissue of patients with BPH. In addition, oxytocin aggravates BPH and the oxytocin-induced proliferative effect on prostatic cells is mediated through the MEK/ERK/RSK pathway, at least partly. Thus, the hypothalamic regulation may be involved in development of BPH, which may open a new door to more medications for BPH in the future. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Development and external validation of a prostate health index-based nomogram for predicting prostate cancer

PubMed Central

Zhu, Yao; Han, Cheng-Tao; Zhang, Gui-Ming; Liu, Fang; Ding, Qiang; Xu, Jian-Feng; Vidal, Adriana C.; Freedland, Stephen J.; Ng, Chi-Fai; Ye, Ding-Wei

2015-01-01

To develop and externally validate a prostate health index (PHI)-based nomogram for predicting the presence of prostate cancer (PCa) at biopsy in Chinese men with prostate-specific antigen 4–10 ng/mL and normal digital rectal examination (DRE). 347 men were recruited from two hospitals between 2012 and 2014 to develop a PHI-based nomogram to predict PCa. To validate these results, we used a separate cohort of 230 men recruited at another center between 2008 and 2013. Receiver operator curves (ROC) were used to assess the ability to predict PCa. A nomogram was derived from the multivariable logistic regression model and its accuracy was assessed by the area under the ROC (AUC). PHI achieved the highest AUC of 0.839 in the development cohort compared to the other predictors (p < 0.001). Including age and prostate volume, a PHI-based nomogram was constructed and rendered an AUC of 0.877 (95% CI 0.813–0.938). The AUC of the nomogram in the validation cohort was 0.786 (95% CI 0.678–0.894). In clinical effectiveness analyses, the PHI-based nomogram reduced unnecessary biopsies from 42.6% to 27% using a 5% threshold risk of PCa to avoid biopsy with no increase in the number of missed cases relative to conventional biopsy decision. PMID:26471350

High-Dose Conformal Radiotherapy Reduces Prostate Cancer-Specific Mortality: Results of a Meta-analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Viani, Gustavo Arruda, E-mail: gusviani@gmail.com; Godoi Bernardes da Silva, Lucas; Stefano, Eduardo Jose

2012-08-01

Purpose: To determine in a meta-analysis whether prostate cancer-specific mortality (PCSM), biochemical or clinical failure (BCF), and overall mortality (OM) in men with localized prostate cancer treated with conformal high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT). Methods and Materials: The MEDLINE, Embase, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing conformal HDRT with CDRT for localized prostate cancer. Results: Five randomized, controlled trials (2508 patients) that met the study criteria were identified. Pooled results from these randomized, controlled trialsmore » showed a significant reduction in the incidence of PCSM and BCF rates at 5 years in patients treated with HDRT (p = 0.04 and p < 0.0001, respectively), with an absolute risk reduction (ARR) of PCSM and BCF at 5 years of 1.7% and 12.6%, respectively. Two trials evaluated PCSM with 10 years of follow up. The pooled results from these trials showed a statistical benefit for HDRT in terms of PCSM (p = 0.03). In the subgroup analysis, trials that used androgen deprivation therapy (ADT) showed an ARR for BCF of 12.9% (number needed to treat = 7.7, p < 0.00001), whereas trials without ADT had an ARR of 13.6% (number needed to treat = 7, p < 0.00001). There was no difference in the OM rate at 5 and 10 years (p = 0.99 and p = 0.11, respectively) between the groups receiving HDRT and CDRT. Conclusions: This meta-analysis is the first study to show that HDRT is superior to CDRT in preventing disease progression and prostate cancer-specific death in trials that used conformational technique to increase the total dose. Despite the limitations of our study in evaluating the role of ADT and HDRT, our data show no benefit for HDRT arms in terms of BCF in trials with or without ADT.« less

Genetics Home Reference: prostate cancer

MedlinePlus

... prostate cancer Genetic Testing Registry: Prostate cancer aggressiveness quantitative trait locus on chromosome 19 Genetic Testing Registry: ... OMIM (25 links) PROSTATE CANCER PROSTATE CANCER AGGRESSIVENESS QUANTITATIVE TRAIT LOCUS ON CHROMOSOME 19 PROSTATE CANCER ANTIGEN ...

Preventive effect of ginsenoid on chronic bacterial prostatitis.

PubMed

Kim, Sang Hoon; Ha, U-Syn; Sohn, Dong Wan; Lee, Seung-Ju; Kim, Hyun Woo; Han, Chang Hee; Cho, Yong-Hyun

2012-10-01

Empirical antibiotic therapy is the preferred primary treatment modality for chronic bacterial prostatitis (CBP). However, this method of treatment has a low success rate and long-term therapy may result in complications and the appearance of resistant strains. Therefore a new alternative method for the prevention of CBP is necessary. There are several reports that ginsenoid has a preventive effect on urinary tract infection (UTI). To evaluate the preventive effect of ginsenoid on CBP compared to conventional antibiotics, we carried out an experiment in a rat model of the disease. Four groups of adult male Wistar rats were treated with the following medications: (1) control (no medication), (2) ciprofloxacin, (3) ginsenoid, and (4) ciprofloxacin/ginsenoid. All medications were given for 4 weeks, and then we created a CBP model in the animals by injecting an Escherichia coli Z17 (O2:K1;H(-)) suspension into the prostatic urethra. After 4 weeks, results of microbiological cultures of prostate and urine samples, as well as histological findings of the prostate in each group were analyzed. The microbiological cultures of the prostate samples demonstrated reduced bacterial growth in all experimental groups compared with the control group. Histopathological examination showed a significantly decreased rate of infiltration of inflammatory cells into prostatic tissue and decreased interstitial fibrosis in the ginsenoid group compared with the control group. Inhibition of prostate infection was greater in the group receiving both ginsenoid and antibiotic than in the single-medication groups. Although the findings of this study suggest a preventive effect of ginsenoid, preventive methods for CBP are still controversial.

Notch signaling dynamics in the adult healthy prostate and in prostatic tumor development.

PubMed

Pedrosa, Ana-Rita; Graça, José L; Carvalho, Sandra; Peleteiro, Maria C; Duarte, António; Trindade, Alexandre

2016-01-01

The Notch signaling pathway has been implicated in prostate development, maintenance and tumorigenesis by its key role in cell-fate determination, differentiation and proliferation. Therefore, we proposed to analyze Notch family members transcription and expression, including ligands (Dll1, 3, 4 and Jagged1 and 2), receptors (Notch1-4) and effectors (Hes1, 2, 5 and Hey1, 2, L), in both normal and tumor bearing mouse prostates to better understand the dynamics of Notch signaling in prostate tumorigenesis. Wild type mice and transgenic adenocarcinoma of the mouse prostate model (TRAMP) mice were sacrificed at 18, 24 or 30 weeks of age and the prostates collected and processed for either whole prostate or prostate cell specific populations mRNA analysis and for protein expression analysis by immunohistochemistry and immunofluorescence. We observed that Dll1 and Dll4 are expressed in the luminal compartment of the mouse healthy prostate, whereas Jagged2 expression is restricted to the basal and stromal compartment. Additionally, Notch2 and Notch4 are normally expressed in the prostate luminal compartment while Notch2 and Notch3 are also expressed in the stromal layer of the healthy prostate. As prostate tumor development takes place, there is up-regulation of Notch components. Particularly, the prostate tumor lesions have increased expression of Jagged1 and 2, of Notch3 and of Hey1. We have also detected the presence of activated Notch3 in prostatic tumors that co-express Jagged1 and ultimately the Hey1 effector. Taken together our results point out the Notch axis Jagged1-2/Notch3/Hey1 to be important for prostate tumor development and worthy of additional functional studies and validation in human clinical disease. © 2015 Wiley Periodicals, Inc.

Pathogenesis of prostate cancer and hormone refractory prostate cancer

PubMed Central

Girling, J. S.; Whitaker, H. C.; Mills, I. G.; Neal, D. E.

2007-01-01

Prostate cancer is the second most common malignancy in males and the leading cause of cancer death. Prostate cancer is initially androgen dependent and relies upon the androgen receptor (AR) to mediate the effects of androgens. The AR is also the target for therapy using antiandrogens and LHRH analogues. However, all cancers eventually become androgen independent, often referred to as hormone refractory prostate cancer. The processes involved in this transformation are yet to be fully understood but research in this area has discovered numerous potential mechanisms including AR amplification, over-expression or mutation and alterations in the AR signaling pathway. This review of the recent literature examines the current knowledge and developments in the understanding of the molecular biology of prostate cancer and hormone refractory prostate cancer, summarizing the well characterized pathways involved as well as introducing new concepts that may offer future solutions to this difficult problem. PMID:19675761

Prognostic Importance of Small Prostate Size in Men Receiving Definitive Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taira, Al V.; Merrick, Gregory S., E-mail: gmerrick@urologicresearchinstitute.org; Galbreath, Robert W.

Purpose: To assess whether small prostate size is an adverse prognostic factor in men undergoing brachytherapy in the same manner in which it seems to be for men undergoing radical prostatectomy. Methods and Materials: From April 1995 to June 2008, 2024 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.4 years. The role of small prostate size ({<=}20 cm{sup 3}) as a prognostic factor for biochemical progression-free survival, cause-specific survival, and all-cause mortality was investigated. The differences in survival between men with small and larger prostates were compared using Kaplan-Meier curves and log-rank tests. Results: Median prostate sizemore » for the entire cohort was 32.7 cm{sup 3}. For the 167 men with small prostates, median prostate size was 17.4 cm{sup 3}. There was no difference in biochemical progression-free survival (95.2% vs 96.2%, P=.603), cause-specific survival (97.7% vs 98.3%, P=.546), or all-cause mortality (78.0% vs 77.2%, P=.838) at 10 years for men with small prostates compared with men with larger prostates. On univariate and multivariate analysis, small prostate size was not associated with any of the primary outcome measures. Conclusion: Men with small prostates treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men with larger glands. High-quality implants with adequate margins seem sufficient to address the increased adverse risk factors associated with small prostate size.« less

Prognostic significance of obstructive uropathy in advanced prostate cancer.

PubMed

Oefelein, Michael G

2004-06-01

To report the incidence and prognostic implications of obstructive uropathy (OU) in patients with advanced prostate cancer receiving androgen deprivation therapy and to define the impact initial local therapy has on the development of OU in patients with prostate cancer who develop recurrence and begin androgen deprivation therapy. From a population of 260 patients with advanced prostate cancer diagnosed between 1986 and 2003, OU was identified in 51 patients. The OU treatment options included ureteral stent, percutaneous nephrostomy, transurethral resection of the prostate, Foley catheter placement, and urinary diversion. Overall survival and the factors that influenced survival were calculated using standard statistical methods. OU was diagnosed in 15 (16%) of 80 patients who received local therapy with curative intent and in whom local therapy subsequently failed and in 36 (19%) of 180 patients who had never received local therapy (P = 0.7, chi-square test). Of these 51 patients, 39 had bladder neck obstruction and 16 had ureteral obstruction. Overall survival was significantly worse for the men with OU compared with those without OU (41 versus 54 months). OU was associated with tumor stage and androgen-insensitive prostate cancer. OU results in significantly reduced survival in men with prostate cancer. In a select group of patients with prostate cancer with progression after local therapy (primarily radiotherapy), no statistically significant reduction in the development of OU was observed relative to patients matched for stage, grade, and pretreatment prostate-specific antigen level treated with androgen deprivation therapy alone. Aggressive advanced stage and hormone-insensitive disease are variables associated with OU.

African Americans' Perceptions of Prostate-Specific Antigen Prostate Cancer Screening

ERIC Educational Resources Information Center

Hunter, Jaimie C.; Vines, Anissa I.; Carlisle, Veronica

2015-01-01

Background: In 2012, the U.S. Preventive Services Task Force released a hotly debated recommendation against prostate-specific antigen testing for all men. The present research examines African Americans' beliefs about their susceptibility to prostate cancer (PCa) and the effectiveness of prostate-specific antigen testing in the context of the…

Outcomes of transurethral resection of the prostate in benign prostatic hyperplasia comparing prostate size of more than 80 grams to prostate size less than 80 grams.

PubMed

Joshi, H N; De Jong, I J; Karmacharya, R M; Shrestha, B; Shrestha, R

2014-01-01

Benign prostatic hyperplasia is a condition occurring in elderly men in which the prostate gland is enlarged, hence the condition also known as benign enlargement of prostate. Benign hyperplasia can lead to both obstructive and irritative symptoms. Transurethral resection of prostate (TURP) still remains the gold standard modality of surgical treatment of obstructive lower urinary tract symptoms due to Benign hyperplasia. The objective of this study was to evaluate the outcomes of TURP in large prostate (>80 grams) in comparison to small prostate (<80 grams) in terms of efficacy, safety and complications. A total of 65 cases included in this prospective study, which were operated by a single surgeon with conventional monopolar TURP using standard technique. Intra -operative and post-operative complications, pre and post- operative quality of life (QoL) and international prostate symptom score (IPSS), operative time, time to removal of catheter and hospital stay were evaluated between small and large prostate gland volumes. Out of 65 cases, 30 were with large prostate size i.e. 80 grams or more (group 1), and 35 cases were with small prostate size than 80 grams size (group 2). Mean age was 71.8 SD ± 6.9 years in group 1 and 68.2 SD ± 12.7 years in group 2. The mean preoperative volume of prostate was 88.8 grams (range 80-115 grams) in group 1 and 40.3 (range 20-65 grams) in group 2. The mean preoperative post void residual volume of urine (PVRU) was 244 ml SD ± 190.8 ml in group 1 and 117 ml ± 70.3 ml in group 2. Mean resection time in group 1 was 110 (range 90-130) minutes and in group 2 it was 90 minutes (range 55-115) minutes. There were quite satisfactory improvements in IPSS and QoL. No significant complications were observed except TUR syndrome in 2 cases from group 2, which were managed well in postoperative period. With meticulous resection and intra-operative haemostasis using continuous out flow resectoscope, conventional monopolar TURP is equally safe

Excessive Antibiotic Utilization in Men with Prostatitis

PubMed Central

Taylor, Brent C.; Noorbaloochi, Siamak; McNaughton-Collins, Mary; Saigal, Christopher S.; Sohn, Min-Woong; Pontari, Michel A.; Litwin, Mark S.; Wilt, Timothy J.

2008-01-01

Background Prostatitis accounts for two million outpatient visits annually. The vast majority of prostatitis cases fit the definition of chronic pelvic pain syndrome for which routine antibiotic use is not indicated. Methods Inpatient, Outpatient, and Pharmacy Datasets from the Veterans Health Administration were used to quantify the magnitude of antibiotic use attributable to chronic pelvic pain syndrome. Specifically, men with a diagnosis of infectious/acute prostatitis, and/or a urinary tract infection were excluded, and the remaining men with a diagnosis of prostatitis were defined as having chronic pelvic pain syndrome. Results Annual prevalence of chronic pelvic pain syndrome was 0.5%. Prescriptions for fluoroquinolone antibiotics were filled in 49% of men with a diagnosis of chronic pelvic pain syndrome compared to five percent in men without chronic pelvic pain syndrome. Men with chronic pelvic pain syndrome were greater than seven times more likely to receive a fluoroquinolone prescription independent of age, race/ethnicity and comorbid conditions. Increased use of other antibiotics was also observed. High utilization was similar in men with either infectious/acute prostatitis or chronic pelvic pain syndrome. Conclusions Despite evidence that antibiotics are not effective in the large majority of men with chronic pelvic pain syndrome, they were prescribed in 69% of men with this diagnosis. Some increased use is probably due to uncontrolled confounding by comorbid conditions or inaccurate diagnostic coding. However, a seven-fold higher rate of fluoroquinolone usage suggests strategies to reduce unnecessary antibiotic use in men with prostatitis are warranted. PMID:18456041

Association Between Travel Distance and Choice of Treatment for Prostate Cancer: Does Geography Reduce Patient Choice?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muralidhar, Vinayak, E-mail: vmuralidhar@partners.org; Rose, Brent S.; Chen, Yu-Wei

Objective: To determine whether the distance between a prostate cancer patient's home and treatment facility was related to the choice of treatment received among those opting for surgery or radiation. Methods and Materials: We identified 222,804 patients diagnosed with National Comprehensive Cancer Network low-, intermediate-, or high-risk N0M0 prostate cancer and treated with local therapy (surgery or radiation alone, with or without hormone therapy) using the National Cancer Database. We used multivariable logistic regression to determine whether the choice of radiation therapy vs radical prostatectomy varied by distance among patients living in rural and urban areas. Analyses were adjusted formore » geographic location within the United States, age, race, Charlson/Deyo comorbidity score, year of diagnosis, income quartile, education quartile, Gleason score, prostate-specific antigen level, and T stage. Results: Patients living in urban or rural areas were less likely to receive radiation compared with surgery if they lived farther from the treatment facility. Among urban patients living ≤5 miles from the treatment facility, 53.3% received radiation, compared with 47.0%, 43.6%, and 33.8% of those living 5 to 10, 10 to 15, or >15 miles away, respectively (P<.001 in all cases). Similarly, rural patients were less likely to receive radiation the farther they lived from the treatment facility (≤25 miles: 62.3%; 25-50 miles: 55.5%; 50-75 miles: 38.4%; >75 miles: 23.8%; P<.05 in all cases). These trends were also present when each risk group was analyzed separately. Conclusion: Patients with prostate cancer in both urban and rural settings were less likely to receive radiation therapy rather than surgery the farther away they lived from a treatment center. These findings raise the possibility that the geographic availability of radiation treatment centers may be an important determinant of whether patients are able to choose radiation rather than surgery for

Association Between Travel Distance and Choice of Treatment for Prostate Cancer: Does Geography Reduce Patient Choice?

PubMed

Muralidhar, Vinayak; Rose, Brent S; Chen, Yu-Wei; Nezolosky, Michelle D; Nguyen, Paul L

2016-10-01

To determine whether the distance between a prostate cancer patient's home and treatment facility was related to the choice of treatment received among those opting for surgery or radiation. We identified 222,804 patients diagnosed with National Comprehensive Cancer Network low-, intermediate-, or high-risk N0M0 prostate cancer and treated with local therapy (surgery or radiation alone, with or without hormone therapy) using the National Cancer Database. We used multivariable logistic regression to determine whether the choice of radiation therapy vs radical prostatectomy varied by distance among patients living in rural and urban areas. Analyses were adjusted for geographic location within the United States, age, race, Charlson/Deyo comorbidity score, year of diagnosis, income quartile, education quartile, Gleason score, prostate-specific antigen level, and T stage. Patients living in urban or rural areas were less likely to receive radiation compared with surgery if they lived farther from the treatment facility. Among urban patients living ≤5 miles from the treatment facility, 53.3% received radiation, compared with 47.0%, 43.6%, and 33.8% of those living 5 to 10, 10 to 15, or >15 miles away, respectively (P<.001 in all cases). Similarly, rural patients were less likely to receive radiation the farther they lived from the treatment facility (≤25 miles: 62.3%; 25-50 miles: 55.5%; 50-75 miles: 38.4%; >75 miles: 23.8%; P<.05 in all cases). These trends were also present when each risk group was analyzed separately. Patients with prostate cancer in both urban and rural settings were less likely to receive radiation therapy rather than surgery the farther away they lived from a treatment center. These findings raise the possibility that the geographic availability of radiation treatment centers may be an important determinant of whether patients are able to choose radiation rather than surgery for localized prostate cancer. Copyright © 2016 Elsevier Inc. All

Biomimetic Synthesis of Macahydantoins A and B from Lepidium meyenii, and Structure Revision of Macahydantoin B as a Class of Thiohydantoin with a 4-Methyl-hexahydropyrrolo[1,2-c]imidazole Skeleton.

PubMed

Zhou, Min; Ma, Hang-Ying; Xing, Huan-Huan; Li, Ping; Li, Gan-Peng; Geng, Hui-Chun; Hu, Qiu-Fen; Yang, Guang-Yu

2017-09-15

Phytochemical investigation on Lepidium meyenii led to the discovery of macahydantoin C (3), a new thiohydantoin with a 1,3-diazabicyclo[3.3.1]nonane core, the spectral properties of which indicate a potential structural misassignment of its previously reported analogue, macahydantoin B (2a). To probe this hypothesis, a concise, scalable, and biomimetic synthesis of the originally proposed 2a and its revised structure (2b) was efficiently accomplished using the modified Edman degradation as the key step from commercially available materials in 65% (three steps) and 52% (three steps) overall yields, respectively. These synthetic endeavors undoubtedly reassigned the structure of macahydantoin B as an unreported type of thiohydantoin featuring a 4-methyl-hexahydropyrrolo[1,2-c]imidazole scaffold.

Prostate Cancer Ambassadors

PubMed Central

Vines, Anissa I.; Hunter, Jaimie C.; Carlisle, Veronica A.; Richmond, Alan N.

2016-01-01

African American men bear a higher burden of prostate cancer than Caucasian men, but knowledge about how to make an informed decision about prostate cancer screening is limited. A lay health advisor model was used to train “Prostate Cancer Ambassadors” on prostate cancer risk and symptoms, how to make an informed decision for prostate-specific antigen screening, and how to deliver the information to members of their community. Training consisted of two, 6-hour interactive sessions and was implemented in three predominantly African American communities over an 8-month period between 2013 and 2014. Following training, Ambassadors committed to contacting at least 10 people within 3 months using a toolkit composed of wallet-sized informational cards for distribution, a slide presentation, and a flip chart. Thirty-two Ambassadors were trained, with more than half being females (59%) and half reporting a family history of prostate cancer. Prostate cancer knowledge improved significantly among Ambassadors (p ≤ .0001). Self-efficacy improved significantly for performing outreach tasks (p < .0001), and among women in helping a loved one with making an informed decision (p = .005). There was also an improvement in collective efficacy in team members (p = .0003). Twenty-nine of the Ambassadors fulfilled their commitment to reach at least 10 people (average number of contacts per Ambassador was 11). In total, 355 individuals were reached with the prostate cancer information. The Ambassador training program proved successful in training Ambassadors to reach communities about prostate cancer and how to make an informed decision about screening. PMID:27099348

(+)-Meyeniins A-C, Novel Hexahydroimidazo[1,5-c]thiazole Derivatives from the Tubers of Lepidium meyenii: Complete Structural Elucidation by Biomimetic Synthesis and Racemic Crystallization.

PubMed

Zhou, Min; Ma, Hang-Ying; Liu, Zhi-Hua; Yang, Guang-Yu; Du, Gang; Ye, Yan-Qing; Li, Gan-Peng; Hu, Qiu-Fen

2017-03-08

(+)-Meyeniins A-C (1-3), a novel class of sulfur-containing hexahydroimidazo[1,5-c]thiazole derivatives, were isolated from the tubers of Lepidium meyenii (maca) cultivated in Lijiang, Yunnan province, China. Guided by their biosynthetic hypothesis, a stereocontrolled biomimetic synthesis of meyeniins A-C and their individual enantiomers was efficiently accomplished by a combination of a condensation reaction and Edman degradation. The formation of high-quality crystals for X-ray crystallography occurred much more readily from a racemic mixture of (±)-meyeniin A than with the single enantiomer alone in this case. These extensive strategies, combined with circular dichroism (CD) spectra, allowed the complete structural assignments of (+)-meyeniins A-C. Among them, (+)-meyeniin A showed moderate selective cytotoxicities against the HL-60, A549 and MCF-7 human cell lines with IC 50 values of 14.41, 32.22, and 33.14 μM, respectively. To some extent, these findings support traditional applications of maca as healthy nutritional supplements or functional foods for cancer prevention.

Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients.

PubMed

Schlick, Bettina; Massoner, Petra; Lueking, Angelika; Charoentong, Pornpimol; Blattner, Mirjam; Schaefer, Georg; Marquart, Klaus; Theek, Carmen; Amersdorfer, Peter; Zielinski, Dirk; Kirchner, Matthias; Trajanoski, Zlatko; Rubin, Mark A; Müllner, Stefan; Schulz-Knappe, Peter; Klocker, Helmut

2016-01-01

Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens. Radical prostatectomy specimens of prostate cancer patients (N = 70) were classified into high and low inflammation groups according to the amount of tissue infiltrating lymphocytes. The corresponding pre-surgery blood serum samples were scrutinized for autoantibodies using a low-density protein array. Selected autoantigens were identified in prostate tissue and their expression pattern analyzed by immunohistochemistry and qPCR. The identified autoantibody profile was cross-checked in an independent sample set (N = 63) using the Luminex-bead protein array technology. Protein array screening identified 165 autoantibodies differentially abundant in the serum of high compared to low inflammation patients. The expression pattern of three corresponding antigens were established in benign and cancer tissue by immunohistochemistry and qPCR: SPAST (Spastin), STX18 (Syntaxin 18) and SPOP (speckle-type POZ protein). Of these, SPAST was significantly increased in prostate tissue with high inflammation. All three autoantigens were differentially expressed in primary and/or castration resistant prostate tumors when analyzed in an inflammation-independent tissue microarray. Cross-validation of the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array, retrieved 51 of the significantly discriminating autoantibodies. Three autoantibodies were significantly upregulated in both screens, MUT, RAB11B and CSRP2 (p>0

Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients

PubMed Central

Schlick, Bettina; Massoner, Petra; Lueking, Angelika; Charoentong, Pornpimol; Blattner, Mirjam; Schaefer, Georg; Marquart, Klaus; Theek, Carmen; Amersdorfer, Peter; Zielinski, Dirk; Kirchner, Matthias; Trajanoski, Zlatko; Rubin, Mark A.; Müllner, Stefan; Schulz-Knappe, Peter; Klocker, Helmut

2016-01-01

Background Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens. Methods Radical prostatectomy specimens of prostate cancer patients (N = 70) were classified into high and low inflammation groups according to the amount of tissue infiltrating lymphocytes. The corresponding pre-surgery blood serum samples were scrutinized for autoantibodies using a low-density protein array. Selected autoantigens were identified in prostate tissue and their expression pattern analyzed by immunohistochemistry and qPCR. The identified autoantibody profile was cross-checked in an independent sample set (N = 63) using the Luminex-bead protein array technology. Results Protein array screening identified 165 autoantibodies differentially abundant in the serum of high compared to low inflammation patients. The expression pattern of three corresponding antigens were established in benign and cancer tissue by immunohistochemistry and qPCR: SPAST (Spastin), STX18 (Syntaxin 18) and SPOP (speckle-type POZ protein). Of these, SPAST was significantly increased in prostate tissue with high inflammation. All three autoantigens were differentially expressed in primary and/or castration resistant prostate tumors when analyzed in an inflammation-independent tissue microarray. Cross-validation of the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array, retrieved 51 of the significantly discriminating autoantibodies. Three autoantibodies were significantly upregulated in both screens, MUT

Matrix-Dependent Regulation of AKT in Hepsin-Overexpressing PC3 Prostate Cancer Cells12

PubMed Central

Wittig-Blaich, Stephanie M; Kacprzyk, Lukasz A; Eismann, Thorsten; Bewerunge-Hudler, Melanie; Kruse, Petra; Winkler, Eva; Strauss, Wolfgang S L; Hibst, Raimund; Steiner, Rudolf; Schrader, Mark; Mertens, Daniel; Sültmann, Holger; Wittig, Rainer

2011-01-01

The serine-protease hepsin is one of the most prominently overexpressed genes in human prostate carcinoma. Forced expression of the enzyme in mice prostates is associated with matrix degradation, invasive growth, and prostate cancer progression. Conversely, hepsin overexpression in metastatic prostate cancer cell lines was reported to induce cell cycle arrest and reduction of invasive growth in vitro. We used a system for doxycycline (dox)-inducible target gene expression in metastasis-derived PC3 cells to analyze the effects of hepsin in a quantitative manner. Loss of viability and adhesion correlated with hepsin expression levels during anchorage-dependent but not anchorage-independent growth. Full expression of hepsin led to cell death and detachment and was specifically associated with reduced phosphorylation of AKT at Ser473, which was restored by growth on matrix derived from RWPE1 normal prostatic epithelial cells. In the chorioallantoic membrane xenograft model, hepsin overexpression in PC3 cells reduced the viability of tumors but did not suppress invasive growth. The data presented here provide evidence that elevated levels of hepsin interfere with cell adhesion and viability in the background of prostate cancer as well as other tissue types, the details of which depend on the microenvironment provided. Our findings suggest that overexpression of the enzyme in prostate carcinogenesis must be spatially and temporally restricted for the efficient development of tumors and metastases. PMID:21750652

Prostate Specific Membrane Antigen (PSMA) Targeted Bio-orthogonal Therapy for Metastatic Prostate Cancer

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-16-1-0595 TITLE: Prostate-Specific Membrane Antigen (PSMA) Targeted Bio -orthogonal Therapy for Metastatic Prostate Cancer...Sep 2016 - 14 Sep 2017 4. TITLE AND SUBTITLE Prostate-Specific Membrane Antigen (PSMA) Targeted Bio -orthogonal Therapy for Metastatic Prostate

Targeting Th17-IL-17 pathway in prevention of micro-invasive prostate cancer in a mouse model

PubMed Central

Zhang, Qiuyang; Liu, Sen; Ge, Dongxia; Cunningham, David M.; Huang, Feng; Ma, Lin; Burris, Thomas P.; You, Zongbing

2017-01-01

Background Chronic inflammation has been associated with the development and progression of human cancers including prostate cancer. The exact role of the inflammatory Th17-IL-17 pathway in prostate cancer remains unknown. In this study, we aimed to determine the importance of Th17 cells and IL-17 in a Pten-null prostate cancer mouse model. Methods The Pten-null mice were treated by Th17 inhibitor SR1001 or anti-mouse IL-17 monoclonal antibody from 6 weeks of age up to 12 weeks of age. For SR1001 treatment, the mice were injected i.p. twice a day with vehicle or SR1001, which was dissolved in a dimethylsulfoxide (DMSO) solution. All mice were euthanized for necropsy at 12 weeks of age. For IL-17 antibody treatment, the mice were injected i.v. once every two weeks with control IgG or rat anti-mouse IL-17 monoclonal antibody, which was dissolved in PBS. The injection time points were at 6, 8, and 10-week-old. All mice were analyzed for the prostate phenotypes at 12 weeks of age. Results We found that either SR1001 or anti-IL-17 antibody treatment decreased the formation of micro-invasive prostate cancer in Pten-null mice. The SR1001 or anti-IL-17 antibody treated mouse prostates had reduced proliferation, increased apoptosis, and reduced angiogenesis, as well as reduced inflammatory cell infiltration. By assessing the epithelial-to-mesenchymal transition (EMT) markers, we found that SR1001 or anti-IL-17 antibody treated prostate tissues had weaker EMT phenotype compared to the control treated prostates. Conclusions These results demonstrated that Th17-IL-17 pathway plays a key role in prostate cancer progression in Pten-null mice. Targeting Th17-IL-17 pathway could prevent micro-invasive prostate cancer formation in mice. PMID:28240383

Therapeutic effect of ACTICOA powder, a cocoa polyphenolic extract, on experimentally induced prostate hyperplasia in Wistar-Unilever rats.

PubMed

Bisson, Jean-François; Hidalgo, Sophie; Rozan, Pascale; Messaoudi, Michaël

2007-12-01

Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate that results in obstructive lower urinary tract symptoms. Plant extracts are frequently used to treat BPH rather than therapeutics that can cause severe side effects. ACTICOA() (Ba0rry Callebaut France, Louviers, France) powder (AP) is a cocoa polyphenolic extract, and we have shown in a previous study that oral treatment with AP prevented prostate hyperplasia. This study investigated whether AP could improve established prostate hyperplasia using the same testosterone propionate (TP)-induced prostate hyperplasia model in rats. Male Wistar-Unilever rats were randomly divided in four groups of 12 rats: one group injected with corn oil and orally treated with the vehicle (negative control) and three groups injected subcutaneously with TP and orally treated with the vehicle (positive control) or AP at 24 (AP24) and 48 (AP48) mg/kg/day. Treatments started 1 week after the start of the induction of prostate hyperplasia and lasted for 2 weeks. The influence of TP and AP on body weights, food and water consumptions, plasma polyphenolic concentration, and serum dihydrotestoterone (DHT) level of rats was examined. At completion of the study, rats were sacrificed, and the prostates were removed, cleaned, and weighed. The prostate size ratio (prostate weight/rat body weight) was then calculated. TP significantly influenced the body weight gain of the rats and their food and water consumptions, while AP reduced significantly these differences in a dose-dependent manner. AP significantly reduced serum DHT level and prostate size ratio in comparison with positive controls also dose-dependently. In conclusion, AP orally administered was effective for reducing established prostate hyperplasia, especially at the dose of 48 mg/kg/day.

Knockout AR in Prostate

DTIC Science & Technology

2006-10-01

enlarged ventral prostates, we evaluated fertility. We found that there were no significant differences in litter-size when either WT or pes-ARKO males...prostate (DLP), ventral prostate (VP) all lobes of prostate (Pr), testes (T), glans penis (Pe); *Pɘ.05, ***Pɘ.001. PI: Chang, Chawnshang 7

Prostate atypia: does repeat biopsy detect clinically significant prostate cancer?

PubMed

Dorin, Ryan P; Wiener, Scott; Harris, Cory D; Wagner, Joseph R

2015-05-01

While the treatment pathway in response to benign or malignant prostate biopsies is well established, there is uncertainty regarding the risk of subsequently diagnosing prostate cancer when an initial diagnosis of prostate atypia is made. As such, we investigated the likelihood of a repeat biopsy diagnosing prostate cancer (PCa) in patients in which an initial biopsy diagnosed prostate atypia. We reviewed our prospectively maintained prostate biopsy database to identify patients who underwent a repeat prostate biopsy within one year of atypia (atypical small acinar proliferation; ASAP) diagnosis between November 1987 and March 2011. Patients with a history of PCa were excluded. Chart review identified patients who underwent radical prostatectomy (RP), radiotherapy (RT), or active surveillance (AS). For some analyses, patients were divided into two subgroups based on their date of service. Ten thousand seven hundred and twenty patients underwent 13,595 biopsies during November 1987-March 2011. Five hundred and sixty seven patients (5.3%) had ASAP on initial biopsy, and 287 (50.1%) of these patients underwent a repeat biopsy within one year. Of these, 122 (42.5%) were negative, 44 (15.3%) had atypia, 19 (6.6%) had prostatic intraepithelial neoplasia, and 102 (35.6%) contained PCa. Using modified Epstein's criteria, 27/53 (51%) patients with PCa on repeat biopsy were determined to have clinically significant tumors. 37 (36.3%) proceeded to RP, 25 (24.5%) underwent RT, and 40 (39.2%) received no immediate treatment. In patients who underwent surgery, Gleason grade on final pathology was upgraded in 11 (35.5%), and downgraded 1 (3.2%) patient. ASAP on initial biopsy was associated with a significant risk of PCa on repeat biopsy in patients who subsequently underwent definitive local therapy. Patients with ASAP should be counseled on the probability of harboring both clinically significant and insignificant prostate cancer. © 2015 Wiley Periodicals, Inc.

The importance of prostate bed tilt during postprostatectomy intensity-modulated radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bell, Linda J., E-mail: Linda.Bell1@health.nsw.gov.au; Faculty of Health Sciences, University of Sydney, Lidcombe, New South Wales; Cox, Jennifer

2014-10-01

Variations in rectal and bladder filling can create a tilt of the prostate bed, which generates the potential for a geographic miss during postprostatectomy radiotherapy. The aim of this study is to assess the effect that bladder and rectum filling has on planning target volume angle, to determine a method to assess prostate bed tilt leading to potential geographic miss, and to discuss possible implementation issues. The cone-beam computed tomography images (n = 377) of 40 patients who received postprostatectomy radiotherapy with intensity-modulated radiotherapy were reviewed. The amount of tilt in the prostate bed was defined as the angle changemore » between 2 surgical clips, one in the upper prostate bed and another in the lower. A potential geographic miss was defined as movement of any clip of more than 1 cm in any direction or 0.5 cm posteriorly when aligned to bone anatomy. Variations in bladder and rectum size were correlated with the degree of prostate bed tilt, and the rate of potential geographic miss was determined. A possible clinical use of prostate bed tilt was then assessed for different imaging techniques. A tilt of more than 10° was seen in 20.2% of images, which resulted in a 57.9% geographic miss rate of the superior clip. When tilt remained within 10°, there was only a 9% rate of geographic miss. Potential geographic miss of the inferior surgical clip was rare, occurring in only 1.9% of all images reviewed. The most common occurrence when the prostate bed tilt increased by more than 10° was a smaller bladder and larger rectum (6.4% of all images). The most common occurrence when the prostate bed tilt decreased by more than 10° was a larger bladder and smaller rectum (1.3% of all images). Significant prostate bed tilt (>± 10°) occurred in more than 20% of images, creating a 58% rate of geographic miss. Greatest prostate bed tilt occurred when the bladder size increased or reduced by more than 2 cm or the superior rectum size increased by

Vitamin D Receptor Protein Expression in Tumor Tissue and Prostate Cancer Progression

PubMed Central

Hendrickson, Whitney K.; Flavin, Richard; Kasperzyk, Julie L.; Fiorentino, Michelangelo; Fang, Fang; Lis, Rosina; Fiore, Christopher; Penney, Kathryn L.; Ma, Jing; Kantoff, Philip W.; Stampfer, Meir J.; Loda, Massimo; Mucci, Lorelei A.; Giovannucci, Edward

2011-01-01

Purpose Data suggest that circulating 25-hydroxyvitamin D [25(OH)D] interacts with the vitamin D receptor (VDR) to decrease proliferation and increase apoptosis for some malignancies, although evidence for prostate cancer is less clear. How VDR expression in tumor tissue may influence prostate cancer progression has not been evaluated in large studies. Patients and Methods We examined protein expression of VDR in tumor tissue among 841 patients with prostate cancer in relation to risk of lethal prostate cancer within two prospective cohorts, the Physicians' Health Study and Health Professionals Follow-Up Study. We also examined the association of VDR expression with prediagnostic circulating 25(OH)D and 1,25-dihydroxyvitamin D levels and with two VDR single nucleotide polymorphisms, FokI and BsmI. Results Men whose tumors had high VDR expression had significantly lower prostate-specific antigen (PSA) at diagnosis (P for trend < .001), lower Gleason score (P for trend < .001), and less advanced tumor stage (P for trend < .001) and were more likely to have tumors harboring the TMPRSS2:ERG fusion (P for trend = .009). Compared with the lowest quartile, men whose tumors had the highest VDR expression had significantly reduced risk of lethal prostate cancer (hazard ratio [HR], 0.17; 95% CI, 0.07 to 0.41). This association was only slightly attenuated after adjustment for Gleason score and PSA at diagnosis (HR, 0.33; 95% CI, 0.13 to 0.83) or, additionally, for tumor stage (HR, 0.37; 95% CI, 0.14 to 0.94). Neither prediagnostic plasma vitamin D levels nor VDR polymorphisms were associated with VDR expression. Conclusion High VDR expression in prostate tumors is associated with a reduced risk of lethal cancer, suggesting a role of the vitamin D pathway in prostate cancer progression. PMID:21537045

Effect of chronic treatment with three varieties of Lepidium meyenii (Maca) on reproductive parameters and DNA quantification in adult male rats.

PubMed

Gasco, M; Aguilar, J; Gonzales, G F

2007-08-01

The aim of this study was to evaluate the chronic effect of different varieties of Lepidium meyenii (Red Maca, Yellow Maca and Black Maca). Male rats were treated by gavage with aqueous extract of each variety of maca equivalent to 1 g hypocotyl kg(-1) body weight (BW) for 84 days. At the end of the treatment, daily sperm production (DSP), epididymal sperm count (ESC) and sperm count in vas deferens (SCVD) were assessed. In addition, testis DNA quantification was also determined. Any toxic effect was assessed in liver and spleen by histological studies. The results indicate that Yellow Maca and Black Maca improved ESC and that three varieties of maca increased the SCVD without affecting DSP. Moreover, testis DNA levels were not affected by treatment with any of the three varieties of maca. Histological picture of the liver in animals treated with the three varieties of maca was similar to that observed in controls. In conclusion, Yellow and Black Maca increased epididymal sperm count after 84 days of treatment without affecting DSP. Maca seems to act as a modulator of sperm count at the reproductive tract level.

Prostate-specific antigen-based prostate cancer screening: Past and future.

PubMed

Alberts, Arnout R; Schoots, Ivo G; Roobol, Monique J

2015-06-01

Prostate-specific antigen-based prostate cancer screening remains a controversial topic. Up to now, there is worldwide consensus on the statement that the harms of population-based screening, mainly as a result of overdiagnosis (the detection of clinically insignificant tumors that would have never caused any symptoms), outweigh the benefits. However, worldwide opportunistic screening takes place on a wide scale. The European Randomized Study of Screening for Prostate Cancer showed a reduction in prostate cancer mortality through prostate-specific antigen based-screening. These population-based data need to be individualized in order to avoid screening in those who cannot benefit and start screening in those who will. For now, lacking a more optimal screening approach, screening should only be started after the process of shared decision-making. The focus of future research is the reduction of unnecessary testing and overdiagnosis by further research to better biomarkers and the value of the multiparametric magnetic resonance imaging, potentially combined in already existing prostate-specific antigen-based multivariate risk prediction models. © 2015 The Japanese Urological Association.

Prostatic Response to Supranutritional Selenium Supplementation: Comparison of the Target Tissue Potency of Selenomethionine vs. Selenium-Yeast on Markers of Prostatic Homeostasis

PubMed Central

Waters, David J.; Shen, Shuren; Kengeri, Seema S.; Chiang, Emily C.; Combs, Gerald F.; Morris, J. Steven; Bostwick, David G.

2012-01-01

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

Non-dietary environmental risk factors in prostate cancer

PubMed Central

Ferrís-i-Tortajada, J; Berbel-Tornero, O; Garcia-i-Castell, J; López-Andreu, J.A.; Sobrino-Najul, E; Ortega-García, J.A.

2016-01-01

Introduction The aim is to update and disclose the main environmental risk factors, excluding dietary factors, involved in the etiopathology of prostate cancer. Materials and methods Bibliographic review of the last 25 years of non-dietary environmental risk factors associated with prostate cancer between 1985 and 2010, obtained from MedLine, CancerLit, Science Citation Index and Embase. The search profiles were Environmental Risk Factors/Tobacco/Infectious-Inflammatory Factors/Pesticides/Vasectomy/Occupational Exposures/ Chemoprevention Agents/Radiation and Prostate Cancer. Results While some non-dietary environmental risk factors increase the risk of acquiring the disease, others decrease it. Of the former, it is worth mentioning exposal to tobacco smoke, chronic infectious-inflammatory prostatic processes and occupational exposure to cadmium, herbicides and pesticides. The first factors that reduce the risk are the use of chemopreventive drugs (Finasterida, Dutasteride) and exposure to ultraviolet solar radiation. With the current data, a vasectomy does not influence the risk of developing the disease. Conclusions The slow process of prostate carcinogenesis is the final result of the interaction of constitutional risk and environmental factors. Non-dietary environmental factors play an important role in the etiopathology of this disease. To appropriately assess the risk factors, extensive case studies that include all the possible variables must be analyzed. PMID:21439685

Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis

PubMed Central

Wan, Lei; Tan, Hsueh-Li; Thomas-Ahner, Jennifer M.; Pearl, Dennis K.; Erdman, John W.; Moran, Nancy E.; Clinton, Steven K.

2014-01-01

Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer. To identify gene expression patterns associated with early testosterone-driven prostate carcinogenesis, which are impacted by dietary tomato and lycopene, wild type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed control or tomato- or lycopene-containing diets from 4-10 wk-of-age. Eight-week-old mice underwent sham surgery, castration, or castration followed by testosterone-repletion (2.5 mg/kg/d initiated 1 wk after castration). Ten-wk-old intact TRAMP mice exhibit early multifocal prostatic intraepithelial neoplasia (PIN). Of the 200 prostate cancer-related genes measured by quantitative NanoString®, 189 are detectable, 164 significantly differ by genotype, 179 by testosterone status, and 30 by diet type (P<0.05). In TRAMP, expression of Birc5, Mki67, Aurkb, Ccnb2, Foxm1, and Ccne2 is greater compared to WT and is decreased by castration. In parallel, castration reduces Ki67-positive staining (P<0.0001) compared to intact and testosterone-repleted TRAMP mice. Expression of genes involved in androgen metabolism/signaling pathways are reduced by lycopene feeding (Srd5a1) and by tomato-feeding (Srd5a2, Pxn, and Srebf1). Additionally, tomato-feeding significantly reduced expression of genes associated with stem cell features, Aldh1a and Ly6a, while lycopene-feeding significantly reduced expression of neuroendocrine differentiation-related genes, Ngfr and Syp. Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early stages of prostate carcinogenesis that are potential mechanistic targets of dietary tomato components. Future studies on androgen signaling/metabolism, stem cell features, and neuroendocrine differentiation pathways may elucidate the mechanisms by which dietary tomato and lycopene impact prostate cancer risk. PMID:25315431

Ornithine Decarboxylase Activity Is Required for Prostatic Budding in the Developing Mouse Prostate

PubMed Central

Gamat, Melissa; Malinowski, Rita L.; Parkhurst, Linnea J.; Steinke, Laura M.; Marker, Paul C.

2015-01-01

The prostate is a male accessory sex gland that produces secretions in seminal fluid to facilitate fertilization. Prostate secretory function is dependent on androgens, although the mechanism by which androgens exert their effects is still unclear. Polyamines are small cationic molecules that play pivotal roles in DNA transcription, translation and gene regulation. The rate-limiting enzyme in polyamine biosynthesis is ornithine decarboxylase, which is encoded by the gene Odc1. Ornithine decarboxylase mRNA decreases in the prostate upon castration and increases upon administration of androgens. Furthermore, testosterone administered to castrated male mice restores prostate secretory activity, whereas administering testosterone and the ornithine decarboxylase inhibitor D,L-α-difluromethylornithine (DFMO) to castrated males does not restore prostate secretory activity, suggesting that polyamines are required for androgens to exert their effects. To date, no one has examined polyamines in prostate development, which is also androgen dependent. In this study, we showed that ornithine decarboxylase protein was expressed in the epithelium of the ventral, dorsolateral and anterior lobes of the adult mouse prostate. Ornithine decarboxylase protein was also expressed in the urogenital sinus (UGS) epithelium of the male and female embryo prior to prostate development, and expression continued in prostatic epithelial buds as they emerged from the UGS. Inhibiting ornithine decarboxylase using DFMO in UGS organ culture blocked the induction of prostatic buds by androgens, and significantly decreased expression of key prostate transcription factor, Nkx3.1, by androgens. DFMO also significantly decreased the expression of developmental regulatory gene Notch1. Other genes implicated in prostatic development including Sox9, Wif1 and Srd5a2 were unaffected by DFMO. Together these results indicate that Odc1 and polyamines are required for androgens to exert their effect in mediating

Organoid culture systems for prostate epithelial tissue and prostate cancer tissue

PubMed Central

Drost, Jarno; Karthaus, Wouter R.; Gao, Dong; Driehuis, Else; Sawyers, Charles L.; Chen, Yu; Clevers, Hans

2016-01-01

Summary This protocol describes a recently developed strategy to generate 3D prostate organoid cultures from healthy mouse and human prostate (either bulk or FAC-sorted single luminal and basal cells), metastatic prostate cancer lesions and circulating tumour cells. Organoids derived from healthy material contain the differentiated luminal and basal cell types, whereas organoids derived from prostate cancer tissue mimic the histology of the tumour. The stepwise establishment of these cultures and the fully defined serum-free conditioned medium that is required to sustain organoid growth are outlined. Organoids established using this protocol can be used to study many different aspects of prostate biology, including homeostasis, tumorigenesis and drug discovery. PMID:26797458

Prostate biopsy

MedlinePlus

... shows that you have a higher than normal prostate specific antigen (PSA) level Your provider discovers a lump or abnormality in your prostate during a digital rectal exam Normal Results Normal ...

Fisetin Enhances Chemotherapeutic Effect of Cabazitaxel against Human Prostate Cancer Cells.

PubMed

Mukhtar, Eiman; Adhami, Vaqar Mustafa; Siddiqui, Imtiaz Ahmad; Verma, Ajit Kumar; Mukhtar, Hasan

2016-12-01

Although treatment of prostate cancer has improved over the past several years, taxanes, such as cabazitaxel, remain the only form of effective chemotherapy that improves survival in patients with metastatic castration-resistant prostate cancer. However, the effectiveness of this class of drugs has been associated with various side effects and drug resistance. We previously reported that fisetin, a hydroxyflavone, is a microtubule-stabilizing agent and inhibits prostate cancer cell proliferation, migration, and invasion and suggested its use as an adjuvant for treatment of prostate and other cancer types. In this study, we investigated the effect of fisetin in combination with cabazitaxel with the objective to achieve maximum therapeutic benefit, reduce dose and toxicity, and minimize or delay the induction of drug resistance and metastasis. Our data show for the first time that a combination of fisetin (20 μmol/L) enhances cabazitaxel (5 nmol/L) and synergistically reduces 22Rν1, PC-3M-luc-6, and C4-2 cell viability and metastatic properties with minimal adverse effects on normal prostate epithelial cells. In addition, the combination of fisetin with cabazitaxel was associated with inhibition of proliferation and enhancement of apoptosis. Furthermore, combination treatment resulted in the inhibition of tumor growth, invasion, and metastasis when assessed in two in vivo xenograft mouse models. These results provide evidence that fisetin may have therapeutic benefit for patients with advanced prostate cancer through enhancing the efficacy of cabazitaxel under both androgen-dependent and androgen-independent conditions. This study underscores the benefit of the combination of fisetin with cabazitaxel for the treatment of advanced and resistant prostate cancer and possibly other cancer types. Mol Cancer Ther; 15(12); 2863-74. ©2016 AACR. ©2016 American Association for Cancer Research.

Tuberculous prostatitis: mimicking a cancer.

PubMed

Aziz, El Majdoub; Abdelhak, Khallouk; Hassan, Farih Moulay

2016-01-01

Genitourinary tuberculosis is a common type of extra-pulmonary tuberculosis . The kidneys, ureter, bladder or genital organs are usually involved. Tuberculosis of the prostate has mainly been described in immune-compromised patients. However, it can exceptionally be found as an isolated lesion in immune-competent patients. Tuberculosis of the prostate may be difficult to differentiate from carcinoma of the prostate and the chronic prostatitis when the prostate is hard and nodular on digital rectal examination and the urine is negative for tuberculosis bacilli. In many cases, a diagnosis of tuberculous prostatitis is made by the pathologist, or the disease is found incidentally after transurethral resection. Therefore, suspicion of tuberculous prostatitis requires a confirmatory biopsy of the prostate. We report the case of 60-year-old man who presented a low urinary tract syndrome. After clinical and biological examination, and imaging, prostate cancer was highly suspected. Transrectal needle biopsy of the prostate was performed and histological examination showed tuberculosis lesions.

Interfraction Prostate Movement in Bone Alignment After Rectal Enema for Radiotherapy

PubMed Central

Seo, Young Eun; Kim, Tae Hyo; Lee, Ki Soo; Cho, Won Yeol; Lee, Hyung-Sik; Hur, Won-Joo

2014-01-01

Purpose To assess the effect of a rectal enema on interfraction prostate movement in bone alignment (BA) for prostate radiotherapy (RT), we analyzed the spatial difference in prostates in a bone-matched setup. Materials and Methods We performed BA retrospectively with data from prostate cancer patients who underwent image-guided RT (IGRT). The prostate was identified with implanted fiducial markers. The setup for the IGRT was conducted with the matching of three fiducial markers on RT planning computed tomography images and those on two oblique kV x-ray images. Offline BA was performed at the same position. The coordinates of a virtual prostate in BA and a real prostate were obtained by use of the ExaxTrac/NovalisBody system, and the distance between them was calculated as the spatial difference. Interfraction prostate displacement was drawn from the comparison of the spatial differences. Results A total of 15 patients with localized prostate cancer treated with curative hypofractionated IGRT were enrolled. A total of 420 fractions were analyzed. The mean of the interfraction prostate displacements after BA was 3.12±2.00 mm (range, 0.20-10.53 mm). The directional difference was profound in the anterior-posterior and supero-inferior directions (2.14±1.73 mm and 1.97±1.44 mm, respectively) compared with the right-left direction (0.26±0.22 mm, p<0.05). The required margin around the clinical target volume was 4.97 mm with the formula of van Herk et al. Conclusions The interfraction prostate displacement was less frequent when a rectal enema was performed before the procedure. A rectal enema can be used to reduce interfraction prostate displacement and resulting clinical target volume-to-planning target volume margin. PMID:24466393

Endoscopic laser incision of the prostate

NASA Astrophysics Data System (ADS)

Gilbert, Peter T. O.

1998-07-01

To reduce morbidity and costs of transurethral incision of the prostate in cases with bladder neck obstruction and insignificant prostatic hyperplasia, a Nd:YAG laser, wavelength 1064 nm, was used for endoscopic tissue vaporization. Twenty seven patients suffering from severe urinary obstructive symptoms due to a high-riding vesical neck, were operated on under general anesthesia. Under endoscopic control and by means of a 600 micrometer lateral- firing quartz fiber two incisions were performed, starring at the 7 o'clock and 5 o'clock position, respectively, of the bladder neck and following the floor of the prostatic urethra to either side of the verumontanum. Vaporization was achieved with the fiber in permanent tissue contact and the laser working at 60 W power in continuous mode. Total energy averaged 10,000 J. No catheter was inserted and all patients were discharged on the same day after the first micturition. Anti-inflammatory agents were administered for two weeks. No serious complications were encountered postoperatively. Results were evaluated by means of clinical examination, uroflowmetry, sonographic measurement of residual urine and the International Prostate Symptom Score (IPSS) questionnaire. Considering a mean follow up of 15 months, all patients experienced considerable improvement of their obstruction, their urinary peak flow averaging 21 ml/s and their IPSS score 6.7 (preoperatively 12.2 ml/s and 21.8, respectively). As compared to the Collings knife, laser-incision of the prostate carries no risk of bleeding, thus obviating the need of catheterization. It can safely be done in an outpatient setting, probably as well under local as under general anesthesia.

Development and external multicenter validation of Chinese Prostate Cancer Consortium prostate cancer risk calculator for initial prostate biopsy.

PubMed

Chen, Rui; Xie, Liping; Xue, Wei; Ye, Zhangqun; Ma, Lulin; Gao, Xu; Ren, Shancheng; Wang, Fubo; Zhao, Lin; Xu, Chuanliang; Sun, Yinghao

2016-09-01

Substantial differences exist in the relationship of prostate cancer (PCa) detection rate and prostate-specific antigen (PSA) level between Western and Asian populations. Classic Western risk calculators, European Randomized Study for Screening of Prostate Cancer Risk Calculator, and Prostate Cancer Prevention Trial Risk Calculator, were shown to be not applicable in Asian populations. We aimed to develop and validate a risk calculator for predicting the probability of PCa and high-grade PCa (defined as Gleason Score sum 7 or higher) at initial prostate biopsy in Chinese men. Urology outpatients who underwent initial prostate biopsy according to the inclusion criteria were included. The multivariate logistic regression-based Chinese Prostate Cancer Consortium Risk Calculator (CPCC-RC) was constructed with cases from 2 hospitals in Shanghai. Discriminative ability, calibration and decision curve analysis were externally validated in 3 CPCC member hospitals. Of the 1,835 patients involved, PCa was identified in 338/924 (36.6%) and 294/911 (32.3%) men in the development and validation cohort, respectively. Multivariate logistic regression analyses showed that 5 predictors (age, logPSA, logPV, free PSA ratio, and digital rectal examination) were associated with PCa (Model 1) or high-grade PCa (Model 2), respectively. The area under the curve of Model 1 and Model 2 was 0.801 (95% CI: 0.771-0.831) and 0.826 (95% CI: 0.796-0.857), respectively. Both models illustrated good calibration and substantial improvement in decision curve analyses than any single predictors at all threshold probabilities. Higher predicting accuracy, better calibration, and greater clinical benefit were achieved by CPCC-RC, compared with European Randomized Study for Screening of Prostate Cancer Risk Calculator and Prostate Cancer Prevention Trial Risk Calculator in predicting PCa. CPCC-RC performed well in discrimination and calibration and decision curve analysis in external validation compared

Hydrogen sulfide mediates the anti-survival effect of sulforaphane on human prostate cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pei, Yanxi; College of Life Science, Shanxi University, Taiyuan; Wu, Bo

2011-12-15

Hydrogen sulfide (H{sub 2}S) is a novel gasotransmitter that regulates cell proliferation and other cellular functions. Sulforaphane (SFN) is a sulfur-containing compound that exhibits anticancer properties, and young sprouts of broccoli are particularly rich in SFN. There is consistent epidemiological evidence that the consumption of sulfur-containing vegetables, such as garlic and cruciferous vegetables, may help reduce the occurrence of prostate cancer. Here we found that a large amount of H{sub 2}S is released when SFN is added into cell culture medium or mixed with mouse liver homogenates, respectively. Both SFN and NaHS (a H{sub 2}S donor) decreased the viability ofmore » PC-3 cells (a human prostate cancer cell line) in a dose-dependent manner, and supplement of methemoglobin or oxidized glutathione (two H{sub 2}S scavengers) reversed SFN-reduced cell viability. We further found both cystathionine gamma-lyase (CSE) and cystathionine beta-synthase are expressed in PC-3 cells and mouse prostate tissues. H{sub 2}S production in prostate tissues from CSE knockout mice was only 20% of that from wild-type mice, suggesting CSE is a major H{sub 2}S-producing enzyme in prostate. CSE overexpression enhanced H{sub 2}S production and inhibited cell viability in PC-3 cells. In addition, both SFN and NaHS activated p38 mitogen-activated protein kinases (MAPK) and c-Jun N-terminal kinase (JNK). Pre-treatment of PC-3 cells with methemoglobin decreased SFN-stimulated MAPK activities. Suppression of both p38 MAPK and JNK reversed H{sub 2}S- or SFN-reduced viability of PC-3 cells. Our results demonstrated that H{sub 2}S mediates the inhibitory effect of SFN on the proliferation of PC-3 cells, which suggests that H{sub 2}S-releasing diet or drug might be beneficial in the treatment of prostate cancer. Highlights: Black-Right-Pointing-Pointer A large amount of H{sub 2}S is released from sulforaphane. Black-Right-Pointing-Pointer H{sub 2}S mediates the anti-survival effect of

Serum ferritin in combination with prostate-specific antigen improves predictive accuracy for prostate cancer.

PubMed

Wang, Xijuan; An, Peng; Zeng, Jiling; Liu, Xiaoyan; Wang, Bo; Fang, Xuexian; Wang, Fudi; Ren, Guoping; Min, Junxia

2017-03-14

Ferritin is highly expressed in many cancer types. Although a few studies have reported an association between high serum ferritin levels and an increased risk of prostate cancer, the results are inconsistent. Therefore, we performed a large case-control study consisting of 2002 prostate cancer patients and 951 control patients with benign prostatic hyperplasia (BPH). We found that high ferritin levels were positively associated with increased serum prostate-specific antigen (PSA) levels and prostate cancer risk; each 100 ng/ml increase in serum ferritin increased the odds ratio (OR) by 1.20 (95% CI: 1.13-1.36). In the prostate cancer group, increased serum ferritin levels were significantly correlated with higher Gleason scores (p < 0.001). Notably, serum PSA values had even higher predictive accuracy among prostate cancer patients with serum ferritin levels > 400 ng/ml (Gleason score + total PSA correlation: r = 0.38; Gleason score + free PSA correlation: r = 0.49). Moreover, using immunohistochemistry, we found that prostate tissue ferritin levels were significantly higher (p < 0.001) in prostate cancer patients (n = 129) compared to BPH controls (n = 31). Prostate tissue ferritin levels were also highly correlated with serum ferritin when patients were classified by cancer severity (r = 0.81). Importantly, we found no correlation between serum ferritin levels and the inflammation marker C-reactive protein (CRP) in prostate cancer patients. In conclusion, serum ferritin is significantly associated with prostate cancer and may serve as a non-invasive biomarker to complement the PSA test in the diagnosis and prognostic evaluation of prostate cancer.

Bioactive maca (Lepidium meyenii) alkamides are a result of traditional Andean postharvest drying practices.

PubMed

Esparza, Eliana; Hadzich, Antonella; Kofer, Waltraud; Mithöfer, Axel; Cosio, Eric G

2015-08-01

Maca, Lepidium meyenii Walpers (Brassicaceae), is an annual herbaceous plant native to the high plateaus of the Peruvian central Andes. Its underground storage hypocotyls have been a traditional medicinal agent and dietary staple since pre-Columbian times. Reported properties include energizing and fertility-enhancing effects. Published reports have focused on the benzylalkamides (macamides) present in dry hypocotyls as one of the main bioactive components. Macamides are secondary amides formed by benzylamine and a fatty acid moiety, with varying hydrocarbon chain lengths and degree of unsaturation. Although it has been assumed that they are usually present in fresh undamaged tissues, analyses show them to be essentially absent from them. However, hypocotyls dried by traditional Andean postharvest practices or industrial oven drying contain up to 800μgg(-1) dry wt (2.3μmolg(-1) dry wt) of macamides. In this study, the generation of macamides and their putative precursors were studied during nine-week traditional drying trials at 4200m altitude and in ovens under laboratory conditions. Freeze-thaw cycles in the open field during drying result in tissue maceration and release of free fatty acids from storage and membrane lipids up to levels of 1200μgg(-1) dry wt (4.3μmolg(-1) dry wt). Endogenous metabolism of the isothiocyanates generated from glucosinolate hydrolysis during drying results in maximal benzylamine values of 4300μgg(-1) dry wt (40.2μmolg(-1) dry wt). Pearson correlation coefficients of the accumulation profiles of benzylamine and free fatty acid to that of macamides showed good values of 0.898 and 0.934, respectively, suggesting that both provide sufficient substrate for amide synthesis during the drying process. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Benign prostate hyperplasia (BPH) - resources

MedlinePlus

Resources - benign prostatic hyperplasia (BPH); Prostate enlargement resources; BPH resources ... organizations provide information on benign prostatic hyperplasia ( prostate enlargement ): National Institute of Diabetes and Digestive and Kidney ...

Targeting Th17-IL-17 Pathway in Prevention of Micro-Invasive Prostate Cancer in a Mouse Model.

PubMed

Zhang, Qiuyang; Liu, Sen; Ge, Dongxia; Cunningham, David M; Huang, Feng; Ma, Lin; Burris, Thomas P; You, Zongbing

2017-06-01

Chronic inflammation has been associated with the development and progression of human cancers including prostate cancer. The exact role of the inflammatory Th17-IL-17 pathway in prostate cancer remains unknown. In this study, we aimed to determine the importance of Th17 cells and IL-17 in a Pten-null prostate cancer mouse model. The Pten-null mice were treated by Th17 inhibitor SR1001 or anti-mouse IL-17 monoclonal antibody from 6 weeks of age up to 12 weeks of age. For SR1001 treatment, the mice were injected intraperitoneally (i.p.) twice a day with vehicle or SR1001, which was dissolved in a dimethylsulfoxide (DMSO) solution. All mice were euthanized for necropsy at 12 weeks of age. For IL-17 antibody treatment, the mice were injected intravenously (i.v.) once every two weeks with control IgG or rat anti-mouse IL-17 monoclonal antibody, which was dissolved in PBS. The injection time points were at 6, 8, and 10 weeks old. All mice were analyzed for the prostate phenotypes at 12 weeks of age. We found that either SR1001 or anti-IL-17 antibody treatment decreased the formation of micro-invasive prostate cancer in Pten-null mice. The SR1001 or anti-IL-17 antibody treated mouse prostates had reduced proliferation, increased apoptosis, and reduced angiogenesis, as well as reduced inflammatory cell infiltration. By assessing the epithelial-to-mesenchymal transition (EMT) markers, we found that SR1001 or anti-IL-17 antibody treated prostate tissues had weaker EMT phenotype compared to the control treated prostates. These results demonstrated that Th17-IL-17 pathway plays a key role in prostate cancer progression in Pten-null mice. Targeting Th17-IL-17 pathway could prevent micro-invasive prostate cancer formation in mice. Prostate 77:888-899, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Genome of Plant Maca (Lepidium meyenii) Illuminates Genomic Basis for High-Altitude Adaptation in the Central Andes.

PubMed

Zhang, Jing; Tian, Yang; Yan, Liang; Zhang, Guanghui; Wang, Xiao; Zeng, Yan; Zhang, Jiajin; Ma, Xiao; Tan, Yuntao; Long, Ni; Wang, Yangzi; Ma, Yujin; He, Yuqi; Xue, Yu; Hao, Shumei; Yang, Shengchao; Wang, Wen; Zhang, Liangsheng; Dong, Yang; Chen, Wei; Sheng, Jun

2016-07-06

Maca (Lepidium meyenii Walp, 2n = 8x = 64), belonging to the Brassicaceae family, is an economic plant cultivated in the central Andes sierra in Peru (4000-4500 m). Considering that the rapid uplift of the central Andes occurred 5-10 million years ago (Ma), an evolutionary question arises regarding how plants such as maca acquire high-altitude adaptation within a short geological period. Here, we report the high-quality genome assembly of maca, in which two closely spaced maca-specific whole-genome duplications (WGDs; ∼6.7 Ma) were identified. Comparative genomic analysis between maca and closely related Brassicaceae species revealed expansions of maca genes and gene families involved in abiotic stress response, hormone signaling pathway, and secondary metabolite biosynthesis via WGDs. The retention and subsequent functional divergence of many duplicated genes may account for the morphological and physiological changes (i.e., small leaf shape and self-fertility) in maca in a high-altitude environment. In addition, some duplicated maca genes were identified with functions in morphological adaptation (i.e., LEAF CURLING RESPONSIVENESS) and abiotic stress response (i.e., GLYCINE-RICH RNA-BINDING PROTEINS and DNA-DAMAGE-REPAIR/TOLERATION 2) under positive selection. Collectively, the maca genome provides useful information to understand the important roles of WGDs in the high-altitude adaptation of plants in the Andes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Androgen receptor and immune inflammation in benign prostatic hyperplasia and prostate cancer

PubMed Central

Izumi, Kouji; Li, Lei; Chang, Chawnshang

2014-01-01

Both benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are frequent diseases in middle-aged to elderly men worldwide. While both diseases are linked to abnormal growth of the prostate, the epidemiological and pathological features of these two prostate diseases are different. BPH nodules typically arise from the transitional zone, and, in contrast, PCa arises from the peripheral zone. Androgen deprivation therapy alone may not be sufficient to cure these two prostatic diseases due to its undesirable side effects. The alteration of androgen receptor-mediated inflammatory signals from infiltrating immune cells and prostate stromal/epithelial cells may play key roles in those unwanted events. Herein, this review will focus on the roles of androgen/androgen receptor signals in the inflammation-induced progression of BPH and PCa. PMID:26594314

MARCKS promotes invasion and is associated with biochemical recurrence in prostate cancer

PubMed Central

Dorris, Emma; O'Neill, Amanda; Hanrahan, Karen; Treacy, Ann; Watson, R. William

2017-01-01

Background Overtreatment of low-grade prostate cancer is a recognised problem for clinicians and patients. However, under-treatment runs the risk of missing the opportunity for cure in those who could benefit. Identification of new biomarkers of disease progression, including metastases, is required to better stratify and appropriately treat these patients. The ability to predict if prostate cancer will recur is an important clinical question that would impact treatment options for patients. Studies in other cancers have associated MARCKS with metastasis. Methods Tissue microarrays of local prostatectomy samples from a cohort of biochemical recurrent and non-biochemical recurrent tumours were assayed for MARCKS protein expression. Prostate cancer cell lines were transfected with siRNA targeting MARCKS or a control and functional endpoints of migration, invasion, proliferation, viability and apoptosis were measured. Actin was visualised by fluorescent microscopy and evidence of a cadherin switch and activation of the AKT pathway were assayed. Results MARCKS was upregulated in biochemical recurrent patients compared to non-biochemical recurrent. Knockdown of MARCKS reduced migration and invasion of prostate cancer cells, reduced MMP9 mRNA expression, as well as decreasing cell spreading and increased cell:cell adhesion in prostate cancer cell colonies. Knockdown of MARCKS had no effect on proliferation, viability or apoptosis of the prostate cancer cells. Conclusions In conclusion, MARCKS promotes migration and invasion and is associated with biochemical recurrence in localised prostate cancer tumours. The mechanisms by which this occurs have yet to be fully elucidated but lack of a cadherin switch indicates it is not via epithelial-to-mesenchymal transition. Actin rearrangement indicates that MARCKS promotes invasion through regulating the architecture of the cell. PMID:29069765

[Drug therapy of benign prostatic hyperplasia].

PubMed

Vahlensieck, W; Fabricius, P G; Hell, U

1996-11-10

BPH patients with Vahlensieck stage II or III disease are suitable for drug treatment. The points of attack are reduction of testosterone, conversion of testosterone to dihydrotestosterone, conversion of testosterone to estrogen using GnRH analogues, antiandrogens and alpha reductase inhibitors or aromatose inhibitors. Furthermore a reduction in obstruction is achieved through the use of phytopharmaceuticals containing 5-lipoxygenase and cyclooxygenase inhibitors. At present, Curcurbitae pepo seeds, Urtica dioica root, Pollinis siccae extract and Sabal serrulata seed extract are approved for the treatment of prostatic diseases in Germany. The use of alpha-1-sympathicolytic treatment may reduce muscular tone in the prostate. Combination of the various modes of action may also offer an effective form of treatment.

Prostate Problems

MedlinePlus

... Prostate Enlargement (Benign Prostatic Hyperplasia) Urinary Diversion Urinary Retention Urine Blockage in Newborns Vesicoureteral Reflux (VUR) The ... Coordinating Committees Strategic Plans & Reports Research Areas FAQs Jobs at NIDDK Visit Us Contact Us News News ...

Prostatitis - nonbacterial

MedlinePlus

... ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 40. Kaplan SA. Benign prostatic hyperplasia and prostatitis. In: Goldman ... constitute endorsements of those other sites. Copyright 1997-2018, A.D.A.M., Inc. Duplication for commercial ...

Prostate Cancer

MedlinePlus

... man's bladder that produces fluid for semen. Prostate cancer is common among older men. It is rare ... younger than 40. Risk factors for developing prostate cancer include being over 65 years of age, family ...

Inhibitory effect of a defensin gene from the Andean crop maca (Lepidium meyenii) against Phytophthora infestans.

PubMed

Solis, Julio; Medrano, Giuliana; Ghislain, Marc

2007-08-01

In this study, we report the isolation of a defensin gene, lm-def, isolated from the Andean crop 'maca' (Lepidium meyenii) with activity against the pathogen Phytophthora infestans responsible of late blight disease of the potato and tomato crops. The lm-def gene has been isolated by polymerase chain reaction (PCR) using degenerate primers corresponding to conserved regions of 13 plant defensin genes of the Brassicaceae family assuming that defensin genes are highly conserved among cruciferous species. The lm-def gene belongs to a small multigene family of at least 10 members possibly including pseudogenes as assessed by genomic hybridization and nucleotide sequence analyses. The deduced mature Lm-Def peptide is 51 amino acids in length and has 74-94% sequence identity with other plant defensins of the Brassicaceae family. The Lm-Def peptide was produced as a fusion protein using the pET-44a expression vector and purified using an immobilized metal ion affinity chromatography. The recombinant protein (NusA:Lm-Def) exhibited in vitro activity against P. infestans. The NusA:Lm-Def protein caused growth inhibition and hyphal damage at concentration not greater than 0.4 microM. In contrast, the NusA protein alone expressed and purified similarly did not show any activity against P. infestans. Therefore, these results indicate that the lm-def gene isolated from maca belong to the plant defensin family with activity against P. infestans. Its expression in potato, as a transgene, might help to control the late blight disease caused by P. infestans with the advantage of being of plant origin.

Prostate-specific antigen and acute myocardial infarction: a possible new intriguing scenario.

PubMed

Patanè, Salvatore; Marte, Filippo

2009-05-29

Prostate-specific antigen (PSA) has been identified as a member of the human kallikrein family of serine proteases and it is an established marker for detection of prostate cancer. Apparently spurious result has been reported in a work about mean serum PSA concentration during acute myocardial infarction with mean serum PSA concentration significantly lower on day 2 than either day 1 or day 3 and it has been reported that these preliminary results could reflect several factors, such as antiinfarctual treatment, reduced physical activity or an acute-phase response. Elevation of prostate-specific antigen has also been reported during acute myocardial infarction in three patients and in another one also after transurethral resection of the prostate (TURP) and without histological diagnosis of prostate cancer. In our report we present three cases of diminution of serum PSA concentration during acute myocardial infarction. Our report extends the evaluation of PSA during acute myocardial infarction. It seems that when elevation of prostate-specific antigen occurs during acute myocardial infarction, coronary lesions are frequent and often more severe than when diminution of prostate-specific antigen occurs during acute myocardial infarction. It opens a possible new intriguing scenario of the role of the prostate-specific antigen in acute myocardial infarction.

Microarray Data Mining for Potential Selenium Targets in Chemoprevention of Prostate Cancer

PubMed Central

ZHANG, HAITAO; DONG, YAN; ZHAO, HONGJUAN; BROOKS, JAMES D.; HAWTHORN, LESLEYANN; NOWAK, NORMA; MARSHALL, JAMES R.; GAO, ALLEN C.; IP, CLEMENT

2008-01-01

Background A previous clinical trial showed that selenium supplementation significantly reduced the incidence of prostate cancer. We report here a bioinformatics approach to gain new insights into selenium molecular targets that might be relevant to prostate cancer chemoprevention. Materials and Methods We first performed data mining analysis to identify genes which are consistently dysregulated in prostate cancer using published datasets from gene expression profiling of clinical prostate specimens. We then devised a method to systematically analyze three selenium microarray datasets from the LNCaP human prostate cancer cells, and to match the analysis to the cohort of genes implicated in prostate carcinogenesis. Moreover, we compared the selenium datasets with two datasets obtained from expression profiling of androgen-stimulated LNCaP cells. Results We found that selenium reverses the expression of genes implicated in prostate carcinogenesis. In addition, we found that selenium could counteract the effect of androgen on the expression of a subset obtained from androgen-regulated genes. Conclusions The above information provides us with a treasure of new clues to investigate the mechanism of selenium chemoprevention of prostate cancer. Furthermore, these selenium target genes could also serve as biomarkers in future clinical trials to gauge the efficacy of selenium intervention. PMID:18548127

Prostate Cancer Epigenome

PubMed Central

Chinaranagari, Swathi; Sharma, Pankaj; Bowen, Nathan J.; Chaudhary, Jaideep

2018-01-01

Prostate cancer is a major health burden within the ever-increasingly aging US population. The molecular mechanisms involved in prostate cancer are diverse and heterogeneous. In this context, epigenetic changes, both global and gene specific, are now an emerging alternate mechanism in disease initiation and progression. The three major risk factors in prostate cancer: age, geographic ancestry, and environment are all influenced by epigenetics and additional significant insight is required to gain an understanding of the underlying mechanisms. The androgen receptor and its downstream effector pathways, central to prostate cancer initiation and progression, are subject to a multitude of epigenetic alterations. In this review we focus on the global perspective of epigenetics and the use of recent next-generation sequencing platforms to interrogate epigenetic changes in the prostate cancer genome. PMID:25421658

Prostate cancer epigenome.

PubMed

Chinaranagari, Swathi; Sharma, Pankaj; Bowen, Nathan J; Chaudhary, Jaideep

2015-01-01

Prostate cancer is a major health burden within the ever-increasingly aging US population. The molecular mechanisms involved in prostate cancer are diverse and heterogeneous. In this context, epigenetic changes, both global and gene specific, are now an emerging alternate mechanism in disease initiation and progression. The three major risk factors in prostate cancer: age, geographic ancestry, and environment are all influenced by epigenetics and additional significant insight is required to gain an understanding of the underlying mechanisms. The androgen receptor and its downstream effector pathways, central to prostate cancer initiation and progression, are subject to a multitude of epigenetic alterations. In this review we focus on the global perspective of epigenetics and the use of recent next-generation sequencing platforms to interrogate epigenetic changes in the prostate cancer genome.

Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) significantly improve prostate cancer detection at initial biopsy in a total PSA range of 2-10 ng/ml.

PubMed

Ferro, Matteo; Bruzzese, Dario; Perdonà, Sisto; Marino, Ada; Mazzarella, Claudia; Perruolo, Giuseppe; D'Esposito, Vittoria; Cosimato, Vincenzo; Buonerba, Carlo; Di Lorenzo, Giuseppe; Musi, Gennaro; De Cobelli, Ottavio; Chun, Felix K; Terracciano, Daniela

2013-01-01

Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2-10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2-10 ng/ml at initial biopsy, outperforming currently used %fPSA.

Prostate Cancer

MedlinePlus

... breast cancer (BRCA1 or BRCA2) or a very strong family history of breast cancer, your risk of prostate cancer may be higher. Obesity. Obese men diagnosed with prostate cancer may be more likely ...

Prostate cancer gene 3 and multiparametric magnetic resonance can reduce unnecessary biopsies: decision curve analysis to evaluate predictive models.

PubMed

Busetto, Gian Maria; De Berardinis, Ettore; Sciarra, Alessandro; Panebianco, Valeria; Giovannone, Riccardo; Rosato, Stefano; D'Errigo, Paola; Di Silverio, Franco; Gentile, Vincenzo; Salciccia, Stefano

2013-12-01

To overcome the well-known prostate-specific antigen limits, several new biomarkers have been proposed. Since its introduction in clinical practice, the urinary prostate cancer gene 3 (PCA3) assay has shown promising results for prostate cancer (PC) detection. Furthermore, multiparametric magnetic resonance imaging (mMRI) has the ability to better describe several aspects of PC. A prospective study of 171 patients with negative prostate biopsy findings and a persistent high prostate-specific antigen level was conducted to assess the role of mMRI and PCA3 in identifying PC. All patients underwent the PCA3 test and mMRI before a second transrectal ultrasound-guided prostate biopsy. The accuracy and reliability of PCA3 (3 different cutoff points) and mMRI were evaluated. Four multivariate logistic regression models were analyzed, in terms of discrimination and the cost benefit, to assess the clinical role of PCA3 and mMRI in predicting the biopsy outcome. A decision curve analysis was also plotted. Repeated transrectal ultrasound-guided biopsy identified 68 new cases (41.7%) of PC. The sensitivity and specificity of the PCA3 test and mMRI was 68% and 49% and 74% and 90%, respectively. Evaluating the regression models, the best discrimination (area under the curve 0.808) was obtained using the full model (base clinical model plus mMRI and PCA3). The decision curve analysis, to evaluate the cost/benefit ratio, showed good performance in predicting PC with the model that included mMRI and PCA3. mMRI increased the accuracy and sensitivity of the PCA3 test, and the use of the full model significantly improved the cost/benefit ratio, avoiding unnecessary biopsies. Copyright © 2013 Elsevier Inc. All rights reserved.