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Sample records for prostate cancer death

  1. Prostate cancer, prostate cancer death, and death from other causes, among men with metabolic aberrations.

    Science.gov (United States)

    Häggström, Christel; Stocks, Tanja; Nagel, Gabriele; Manjer, Jonas; Bjørge, Tone; Hallmans, Göran; Engeland, Anders; Ulmer, Hanno; Lindkvist, Björn; Selmer, Randi; Concin, Hans; Tretli, Steinar; Jonsson, Håkan; Stattin, Pär

    2014-11-01

    Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes. In the Metabolic Syndrome and Cancer Project, prospective data on body mass index, blood pressure, glucose, cholesterol, and triglycerides were collected from 285,040 men. Risks of prostate cancer diagnosis, prostate cancer death, and death from other causes were calculated by use of competing risk analysis for men with normal (bottom 84%) and high (top 16%) levels of each factor, and a composite score. During a mean follow-up period of 12 years, 5,893 men were diagnosed with prostate cancer, 1,013 died of prostate cancer, and 26,328 died of other causes. After 1996, when prostate-specific antigen testing was introduced, men up to age 80 years with normal metabolic levels had 13% risk of prostate cancer, 2% risk of prostate cancer death, and 30% risk of death from other causes, whereas men with metabolic aberrations had corresponding risks of 11%, 2%, and 44%. In contrast to recent studies using conventional survival analysis, in a real-world scenario taking risk of competing events into account, men with metabolic aberrations had lower risk of prostate cancer diagnosis, similar risk of prostate cancer death, and substantially higher risk of death from other causes compared with men who had normal metabolic levels.

  2. Relative Risks for Lethal Prostate Cancer Based on Complete Family History of Prostate Cancer Death.

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    Albright, Frederick S; Stephenson, Robert A; Agarwal, Neeraj; Cannon-Albright, Lisa A

    2017-01-01

    There are few published familial relative risks (RR) for lethal prostate cancer. This study estimates RRs for lethal prostate cancer based on comprehensive family history data, with the goal of improving identification of those men at highest risk of dying from prostate cancer. We used a population-based genealogical resource linked to a statewide electronic SEER cancer registry and death certificates to estimate relative risks (RR) for death from prostate cancer based upon family history. Over 600,000 male probands were analyzed, representing a variety of family history constellations of lethal prostate cancer. RR estimates were based on the ratio of the observed to the expected number of lethal prostate cancer cases using internal rates. RRs for lethal prostate cancer based on the number of affected first-degree relatives (FDR) ranged from 2.49 (95% CI: 2.27, 2.73) for exactly 1 FDR to 5.30 (2.13, 10.93) for ≥3 affected FDRs. In an absence of affected FDRs, increased risk was also significant for increasing numbers of affected second-degree or third degree relatives. Equivalent risks were observed for similar maternal and paternal family history. This study provides population-based estimates of lethal prostate cancer risk based on lethal prostate cancer family history. Many family history constellations associated with two to greater than five times increased risk for lethal prostate cancer were identified. These lethal prostate cancer risk estimates hold potential for use in identification, screening, early diagnosis, and treatment of men at high risk for death from prostate cancer. Prostate77:41-48, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. [Causes of death among prostate cancer patients of different ages].

    Science.gov (United States)

    Dariy, E V

    2016-02-01

    To date, there is no unified approach to evaluating and treating patients with suspected prostate cancer taking into account their age and comorbidities. That was the rationale for conducting this study. To assess the clinical course of prostate cancer in men of all ages with comorbidities. The study included 408 patients aged 50 to 92 years (mean age 74.3 years) with histologically verified prostate cancer. 30 (7.4%) patients had stage T1 disease, 273 (66.9%) - T2, 91 (22.3%) - T3 and 14 (3.4%) - T4. The maximum follow-up was 22 years, the minimum one - 6 months (on average 15.4 years). During the follow-up 159 patients died (39%), 51 of them (32%) of prostate cancer, 108 (68%) - from other diseases. Among the latter the causes of death were cancer (20.4%), cardiovascular and bronchopulmonary diseases (79.6%). Cancer-specific survival rate was 41.4 +/-12,4%, the survival rate for other diseases 23.4 +/-10,6% (pcancer, especially of old age, including the option for active surveillance of patients with clinically insignificant prostate cancer.

  4. Ursodeoxycholic Acid Induces Death Receptor-mediated Apoptosis in Prostate Cancer Cells

    Science.gov (United States)

    Lee, Won Sup; Jung, Ji Hyun; Panchanathan, Radha; Yun, Jeong Won; Kim, Dong Hoon; Kim, Hye Jung; Kim, Gon Sup; Ryu, Chung Ho; Shin, Sung Chul; Hong, Soon Chan; Choi, Yung Hyun; Jung, Jin-Myung

    2017-01-01

    Background Bile acids have anti-cancer properties in a certain types of cancers. We determined anticancer activity and its underlying molecular mechanism of ursodeoxycholic acid (UDCA) in human DU145 prostate cancer cells. Methods Cell viability was measured with an MTT assay. UDCA-induced apoptosis was determined with flow cytometric analysis. The expression levels of apoptosis-related signaling proteins were examined with Western blotting. Results UDCA treatment significantly inhibited cell growth of DU145 in a dose-dependent manner. It induced cellular shrinkage and cytoplasmic blebs and accumulated the cells with sub-G1 DNA contents. Moreover, UDCA activated caspase 8, suggesting that UDCA-induced apoptosis is associated with extrinsic pathway. Consistent to this finding, UDCA increased the expressions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor, death receptor 4 (DR4) and death receptor 5 (DR5), and TRAIL augmented the UDCA-induced cell death in DU145 cells. In addition, UDCA also increased the expressions of Bax and cytochrome c and decreased the expression of Bcl-xL in DU145 cells. This finding suggests that UDCA-induced apoptosis may be involved in intrinsic pathway. Conclusions UDCA induces apoptosis via extrinsic pathway as well as intrinsic pathway in DU145 prostate cancer cells. UDCA may be a promising anti-cancer agent against prostate cancer. PMID:28382282

  5. The calcimimetic R-568 induces apoptotic cell death in prostate cancer cells

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    Cheng Guangming

    2009-07-01

    Full Text Available Abstract Background Increased serum level of parathyroid hormone (PTH was found in metastatic prostate cancers. Calcimimetic R-568 was reported to reduce PTH expression, to suppress cell proliferation and to induce apoptosis in parathyroid cells. In this study, we investigated the effect of R-568 on cellular survival of prostate cancer cells. Methods Prostate cancer cell lines LNCaP and PC-3 were used in this study. Cellular survival was determined with MTT, trypan blue exclusion and fluorescent Live/Death assays. Western blot assay was utilized to assess apoptotic events induced by R-568 treatment. JC-1 staining was used to evaluate mitochondrial membrane potential. Results In cultured prostate cancer LNCaP and PC-3 cells, R-568 treatment significantly reduced cellular survival in a dose- and time-dependent manner. R-568-induced cell death was an apoptotic event, as evidenced by caspase-3 processing and PARP cleavage, as well as JC-1 color change in mitochondria. Knocking down calcium sensing receptor (CaSR significantly reduced R-568-induced cytotoxicity. Enforced expression of Bcl-xL gene abolished R-568-induced cell death, while loss of Bcl-xL expression led to increased cell death in R-568-treated LNCaP cells,. Conclusion Taken together, our data demonstrated that calcimimetic R-568 triggers an intrinsic mitochondria-related apoptotic pathway, which is dependent on the CaSR and is modulated by Bcl-xL anti-apoptotic pathway.

  6. Twenty-year Risk of Prostate Cancer Death by Midlife Prostate-specific Antigen and a Panel of Four Kallikrein Markers in a Large Population-based Cohort of Healthy Men.

    Science.gov (United States)

    Sjoberg, Daniel D; Vickers, Andrew J; Assel, Melissa; Dahlin, Anders; Poon, Bing Ying; Ulmert, David; Lilja, Hans

    2018-06-01

    Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. Study based on the Malmö Diet and Cancer cohort enrolling 11 506 unscreened men aged 45-73 yr during 1991-1996, providing cryopreserved blood at enrollment and followed without PSA screening to December 31, 2014. We measured four kallikrein markers in the blood of 1223 prostate cancer cases and 3028 controls. Prostate cancer death (n=317) by PSA and a prespecified statistical model based on the levels of four kallikrein markers. Baseline PSA predicted prostate cancer death with a concordance index of 0.86. In men with elevated PSA (≥2.0ng/ml), predictive accuracy was enhanced by the four-kallikrein panel compared with PSA (0.80 vs 0.73; improvement 0.07; 95% confidence interval 0.04, 0.10). Nearly half of men aged 60+ yr with elevated PSA had a four-kallikrein panel score of four-kallikrein panel score of ≥7.5% had a 13% risk of prostate cancer death at 15 yr. A prespecified statistical model based on four kallikrein markers (commercially available as the 4Kscore) reclassified many men with modestly elevated PSA, to have a low long-term risk of prostate cancer death. Men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  7. Primary Causes of Death After Permanent Prostate Brachytherapy

    International Nuclear Information System (INIS)

    Bittner, Nathan; Merrick, Gregory S.; Galbreath, Robert W.; Butler, Wayne M.; Wallner, Kent E.; Allen, Zachariah A.; Brammer, Sarah G.; Moyad, Mark

    2008-01-01

    Purpose: To evaluate the primary causes of death in low-risk (low-risk), intermediate-risk (intermediate-risk), and high-risk (high-risk) patients undergoing permanent prostate brachytherapy with or without supplemental therapies. Methods and Materials: From April 1995 through November 2004, a total of 1,354 consecutive patients underwent prostate brachytherapy. All patients underwent brachytherapy >3 years before analysis. Of the patients, 532 (39.3%) received androgen deprivation therapy and 703 (51.9%) received supplemental radiation therapy. The median follow-up was 5.4 years. Multiple parameters were evaluated as predictors of cause-specific, biochemical progression-free, and overall survival. Results: The 10-year cause-specific survival was 97.0% (99.7%, 99.0%, and 90.1% for low-risk, intermediate-risk, and high-risk patients). Overall survival was 76.7% (82.5%, 78.3%, and 67.6% for low-, intermediate-, and high-risk patients, respectively). The cumulative death rate for cardiovascular disease was 11.5% (8.7%, 9.3%, and 19.8% for low-, intermediate-, and high-risk patients). The death rate from second malignancies (nonprostate cancer) was 7.2% and was not substantially different when stratified by risk group. Death from all other causes was 6.5% for the entire cohort but 1.3%, 5.0%, and 10.8% for low-, intermediate-, and high-risk patients. In multivariate analysis, death from prostate cancer was best predicted by Gleason score and risk group, whereas death from cardiovascular disease, nonprostate cancer, and all other causes were most closely related to patient age and tobacco use. Conclusions: Although cardiovascular mortality was the predominant cause of death, prostate cancer was responsible for approximately 10% of all deaths. In particular, overall survival was poorest in the high-risk group. Although high-risk patients were most likely to die of prostate cancer, the divergence in overall survival between high-risk and lower-risk patients primarily

  8. Genistein cooperates with the histone deacetylase inhibitor vorinostat to induce cell death in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Phillip Cornel J

    2012-04-01

    Full Text Available Abstract Background Among American men, prostate cancer is the most common, non-cutaneous malignancy that accounted for an estimated 241,000 new cases and 34,000 deaths in 2011. Previous studies have suggested that Wnt pathway inhibitory genes are silenced by CpG hypermethylation, and other studies have suggested that genistein can demethylate hypermethylated DNA. Genistein is a soy isoflavone with diverse effects on cellular proliferation, survival, and gene expression that suggest it could be a potential therapeutic agent for prostate cancer. We undertook the present study to investigate the effects of genistein on the epigenome of prostate cancer cells and to discover novel combination approaches of other compounds with genistein that might be of translational utility. Here, we have investigated the effects of genistein on several prostate cancer cell lines, including the ARCaP-E/ARCaP-M model of the epithelial to mesenchymal transition (EMT, to analyze effects on their epigenetic state. In addition, we investigated the effects of combined treatment of genistein with the histone deacetylase inhibitor vorinostat on survival in prostate cancer cells. Methods Using whole genome expression profiling and whole genome methylation profiling, we have determined the genome-wide differences in genetic and epigenetic responses to genistein in prostate cancer cells before and after undergoing the EMT. Also, cells were treated with genistein, vorinostat, and combination treatment, where cell death and cell proliferation was determined. Results Contrary to earlier reports, genistein did not have an effect on CpG methylation at 20 μM, but it did affect histone H3K9 acetylation and induced increased expression of histone acetyltransferase 1 (HAT1. In addition, genistein also had differential effects on survival and cooperated with the histone deacteylase inhibitor vorinostat to induce cell death and inhibit proliferation. Conclusion Our results suggest that

  9. IκBα mediates prostate cancer cell death induced by combinatorial targeting of the androgen receptor

    International Nuclear Information System (INIS)

    Carter, Sarah Louise; Centenera, Margaret Mary; Tilley, Wayne Desmond; Selth, Luke Ashton; Butler, Lisa Maree

    2016-01-01

    Combining different clinical agents to target multiple pathways in prostate cancer cells, including androgen receptor (AR) signaling, is potentially an effective strategy to improve outcomes for men with metastatic disease. We have previously demonstrated that sub-effective concentrations of an AR antagonist, bicalutamide, and the histone deacetylase inhibitor, vorinostat, act synergistically when combined to cause death of AR-dependent prostate cancer cells. In this study, expression profiling of human prostate cancer cells treated with bicalutamide or vorinostat, alone or in combination, was employed to determine the molecular mechanisms underlying this synergistic action. Cell viability assays and quantitative real time PCR were used to validate identified candidate genes. A substantial proportion of the genes modulated by the combination of bicalutamide and vorinostat were androgen regulated. Independent pathway analysis identified further pathways and genes, most notably NFKBIA (encoding IκBα, an inhibitor of NF-κB and p53 signaling), as targets of this combinatorial treatment. Depletion of IκBα by siRNA knockdown enhanced apoptosis of prostate cancer cells, while ectopic overexpression of IκBα markedly suppressed cell death induced by the combination of bicalutamide and vorinostat. These findings implicate IκBα as a key mediator of the apoptotic action of this combinatorial AR targeting strategy and a promising new therapeutic target for prostate cancer. The online version of this article (doi:10.1186/s12885-016-2188-2) contains supplementary material, which is available to authorized users

  10. Prostate Cancer Screening Results from PLCO

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    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.

  11. Time to second prostate specific antigen (PSA) failure is a surrogate endpoint for prostate cancer death in prospective trials of therapy for localized disease

    Energy Technology Data Exchange (ETDEWEB)

    Zietman, A L; Dallow, K C; Shipley, W U; Heney, N M; McManus, P L

    1995-07-01

    Purpose In assessing the efficacy of the competing curative therapies for prostate cancer the most relevant endpoint is cancer specific death. Due to the long natural history of the disease and the use of salvage androgen suppression prospective trials need to mature for at least a decade to provide meaningful results. An endpoint that predicted for cancer death with high probability would allow more rapid completion of prospective studies, hopefully before the tested therapies become outdated. Materials and methods 202 patients entered into a single institution prospective randomized study for T3-4 prostate cancer between 1982 and 1992 were evaluated. All received radical irradiation to either a standard dose of 67.2Gy or a higher dose of 75.6Gy (the latter employing a proton beam boost). 76 men have received androgen suppression or orchiectomy for salvage following relapse (median follow-up 6.9 years). Of this group 35 experienced a second relapse heralded by a rise in the serum PSA. Second failure was scored on the date that the serum PSA rose to greater than 10% above the post-androgen suppression nadir. Kaplan-Meier analysis was made of survival from the time of second PSA failure and the cause of death established in all patients who subsequently died. Results The median duration of response to hormone therapy following first failure was 27.2 months. The actuarial survival from the time of second biochemical relapse was 93%, 66%, 35%, and 0% at 1, 2, 3, and 4 years respectively (50% at 32 months). 16 patients have so far died after second failure all from causes related to their prostate cancer. Conclusion Second PSA failure appears to be a secure surrogate for impending prostate cancer death. Its use as an endpoint in prospective studies should allow earlier reporting by 2 - 3 years.

  12. Cyproterone acetate enhances TRAIL-induced androgen-independent prostate cancer cell apoptosis via up-regulation of death receptor 5.

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    Chen, Linjie; Wolff, Dennis W; Xie, Yan; Lin, Ming-Fong; Tu, Yaping

    2017-03-07

    Virtually all prostate cancer deaths occur due to obtaining the castration-resistant phenotype after prostate cancer cells escaped from apoptosis and/or growth suppression initially induced by androgen receptor blockade. TNF-related apoptosis-inducing ligand (TRAIL) was an attractive cancer therapeutic agent due to its minimal toxicity to normal cells and remarkable apoptotic activity in tumor cells. However, most localized cancers including prostate cancer are resistant to TRAIL-induced apoptosis, thereby creating a therapeutic challenge of inducing TRAIL sensitivity in cancer cells. Herein the effects of cyproterone acetate, an antiandrogen steroid, on the TRAIL-induced apoptosis of androgen receptor-negative prostate cancer cells are reported. Cell apoptosis was assessed by both annexin V/propidium iodide labeling and poly (ADP-ribose) polymerase cleavage assays. Gene and protein expression changes were determined by quantitative real-time PCR and western blot assays. The effect of cyproterone acetate on gene promoter activity was determined by luciferase reporter assay. Cyproterone acetate but not AR antagonist bicalutamide dramatically increased the susceptibility of androgen receptor-negative human prostate cancer PC-3 and DU145 cells to TRAIL-induced apoptosis but no effects on immortalized human prostate stromal PS30 cells and human embryonic kidney HEK293 cells. Further investigation of the TRAIL-induced apoptosis pathway revealed that cyproterone acetate exerted its effect by selectively increasing death receptor 5 (DR5) mRNA and protein expression. Cyproterone acetate treatment also increased DR5 gene promoter activity, which could be abolished by mutation of a consensus binding domain of transcription factor CCAAT-enhancer-binding protein homologous protein (CHOP) in the DR5 gene promoter. Cyproterone acetate increases CHOP expression in a concentration and time-dependent manner and endoplasmic reticulum stress reducer 4-phenylbutyrate could block

  13. Corn silk maysin induces apoptotic cell death in PC-3 prostate cancer cells via mitochondria-dependent pathway.

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    Lee, Jisun; Lee, Seul; Kim, Sun-Lim; Choi, Ji Won; Seo, Jeong Yeon; Choi, Doo Jin; Park, Yong Il

    2014-12-05

    Despite recent advances in prostate cancer diagnostics and therapeutics, the overall survival rate still remains low. This study was aimed to assess potential anti-cancer activity of maysin, a major flavonoid of corn silk (CS, Zea mays L.), in androgen-independent human prostate cancer cells (PC-3). Maysin was isolated from CS of Kwangpyeongok, a Korean hybrid corn, via methanol extraction and preparative C18 reverse phase column chromatography. Maysin cytotoxicity was determined by either monitoring cell viability in various cancer cell lines by MTT assay or morphological changes. Apoptotic cell death was assessed by annexin V-FITC/PI double staining, depolarization of mitochondrial membrane potential (MMP), expression levels of Bcl-2 and pro-caspase-3 and by terminal transferase mediated dUTP-fluorescein nick end labeling (TUNEL) staining. Underlying mechanism in maysin-induced apoptosis of PC-3 cells was explored by evaluating its effects on Akt and ERK pathway. Maysin dose-dependently reduced the PC-3 cell viability, with an 87% reduction at 200 μg/ml. Maysin treatment significantly induced apoptotic cell death, DNA fragmentation, depolarization of MMP, and reduction in Bcl-2 and pro-caspase-3 expression levels. Maysin also significantly attenuated phosphorylation of Akt and ERK. A combined treatment with maysin and other known anti-cancer agents, including 5-FU, etoposide, cisplatin, or camptothecin, synergistically enhanced PC-3 cell death. These results suggested for the first time that maysin inhibits the PC-3 cancer cell growth via stimulation of mitochondria-dependent apoptotic cell death and may have a strong therapeutic potential for the treatment of either chemo-resistant or androgen-independent human prostate cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Transrectal ultrasound imaging and prostate cancer

    NARCIS (Netherlands)

    Goossen, Tjerk; Wijkstra, Hessel

    2003-01-01

    Prostate cancer is one of the most important causes of death from cancer in men. Ultrasound imaging is frequently used in the diagnosis of prostate cancer. This paper presents an overview of currently available ultrasound imaging techniques. The underlying principles and methods are discussed

  15. A three-protein biomarker panel assessed in diagnostic tissue predicts death from prostate cancer for men with localized disease

    International Nuclear Information System (INIS)

    Severi, Gianluca; FitzGerald, Liesel M; Muller, David C; Pedersen, John; Longano, Anthony; Southey, Melissa C; Hopper, John L; English, Dallas R; Giles, Graham G; Mills, John

    2014-01-01

    Only a minority of prostate cancers lead to death. Because no tissue biomarkers of aggressiveness other than Gleason score are available at diagnosis, many nonlethal cancers are treated aggressively. We evaluated whether a panel of biomarkers, associated with a range of disease outcomes in previous studies, could predict death from prostate cancer for men with localized disease. Using a case-only design, subjects were identified from three Australian epidemiological studies. Men who had died of their disease, “cases” (N = 83), were matched to “referents” (N = 232), those who had not died of prostate cancer, using incidence density sampling. Diagnostic tissue was retrieved to assess expression of AZGP1, MUC1, NKX3.1, p53, and PTEN by semiquantitative immunohistochemistry (IHC). Poisson regression was used to estimate mortality rate ratios (MRRs) adjusted for age, Gleason score, and stage and to estimate survival probabilities. Expression of MUC1 and p53 was associated with increased mortality (MRR 2.51, 95% CI 1.14–5.54, P = 0.02 and 3.08, 95% CI 1.41–6.95, P = 0.005, respectively), whereas AZGP1 expression was associated with decreased mortality (MRR 0.44, 95% CI 0.20–0.96, P = 0.04). Analyzing all markers under a combined model indicated that the three markers were independent predictors of prostate cancer death and survival. For men with localized disease at diagnosis, assessment of AZGP1, MUC1, and p53 expression in diagnostic tissue by IHC could potentially improve estimates of risk of dying from prostate cancer based only on Gleason score and clinical stage

  16. Epigenetic modifications in prostate cancer.

    Science.gov (United States)

    Ngollo, Marjolaine; Dagdemir, Aslihan; Karsli-Ceppioglu, Seher; Judes, Gaelle; Pajon, Amaury; Penault-Llorca, Frederique; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique J

    2014-01-01

    Prostate cancer is the most common cancer in men and the second leading cause of cancer deaths in men in France. Apart from the genetic alterations in prostate cancer, epigenetics modifications are involved in the development and progression of this disease. Epigenetic events are the main cause in gene regulation and the three most epigenetic mechanisms studied include DNA methylation, histone modifications and microRNA expression. In this review, we summarized epigenetic mechanisms in prostate cancer. Epigenetic drugs that inhibit DNA methylation, histone methylation and histone acetylation might be able to reactivate silenced gene expression in prostate cancer. However, further understanding of interactions of these enzymes and their effects on transcription regulation in prostate cancer is needed and has become a priority in biomedical research. In this study, we summed up epigenetic changes with emphasis on pharmacologic epigenetic target agents.

  17. Epigenetics in Prostate Cancer

    OpenAIRE

    Albany, Costantine; Alva, Ajjai S.; Aparicio, Ana M.; Singal, Rakesh; Yellapragada, Sarvari; Sonpavde, Guru; Hahn, Noah M.

    2011-01-01

    Prostate cancer (PC) is the most commonly diagnosed nonskin malignancy and the second most common cause of cancer death among men in the United States. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequences. Two common epigenetic mechanisms, DNA methylation and histone modification, have demonstrated critical roles in prostate cancer growth and metastasis. DNA hypermethylation of cytosine-guanine (CpG) rich sequ...

  18. Prostate radiation in non-metastatic castrate refractory prostate cancer provides an interesting insight into biology of prostate cancer

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    Pascoe Abigail C

    2012-03-01

    Full Text Available Abstract Background The natural history of non-metastatic castrate refractory prostate cancer is unknown and treatment options are limited. We present a retrospective review of 13 patients with locally advanced or high risk prostate cancer, initially treated with hormone monotherapy and then treated with prostate radiation after becoming castration refractory. Findings Median PSA response following prostate radiation was 67.4%. Median time to biochemical progression following radiotherapy was 15 months and to detection of metastatic disease was 18.5 months. Median survival from castration resistance (to date of death or November 2011 was 60 months, with median survival from RT 42 months. Conclusion Prostate radiation appears to be beneficial even in patients with potential micrometastatic disease, which supports the hypothesis that the primary tumour is important in the progression of prostate cancer. These results are an interesting addition to the literature on the biology of prostate cancer especially as this data is unlikely to be available in the future due to combined prostate radiation and androgen deprivation therapy now being the standard of care.

  19. Prostate Cancer Stem-Like Cells | Center for Cancer Research

    Science.gov (United States)

    Prostate cancer is the third leading cause of cancer-related death among men, killing an estimated 27,000 men each year in the United States. Men with advanced prostate cancer often become resistant to conventional therapies. Many researchers speculate that the emergence of resistance is due to the presence of cancer stem cells, which are believed to be a small subpopulation

  20. Medicare Spending for Breast, Prostate, Lung, and Colorectal Cancer Patients in the Year of Diagnosis and Year of Death.

    Science.gov (United States)

    Chen, Christopher T; Li, Ling; Brooks, Gabriel; Hassett, Michael; Schrag, Deborah

    2017-07-26

    To characterize spending patterns for Medicare patients with incident breast, prostate, lung, and colorectal cancer. 2007-2012 data from the Surveillance, Epidemiology, and End Results Program linked with Medicare fee-for-service claims. We calculate per-patient monthly and yearly mean and median expenditures, by cancer type, stage at diagnosis, and spending category, over the years of diagnosis and death. Over the year of diagnosis, mean spending was $35,849, $26,295, $55,597, and $63,063 for breast, prostate, lung, and colorectal cancer, respectively. Over the year of death, spending was similar across different cancer types and stage at diagnosis. Characterization of Medicare spending according to clinically meaningful categories may assist development of oncology alternative payment models and cost-effectiveness models. © Health Research and Educational Trust.

  1. Epigenetics in prostate cancer.

    Science.gov (United States)

    Albany, Costantine; Alva, Ajjai S; Aparicio, Ana M; Singal, Rakesh; Yellapragada, Sarvari; Sonpavde, Guru; Hahn, Noah M

    2011-01-01

    Prostate cancer (PC) is the most commonly diagnosed nonskin malignancy and the second most common cause of cancer death among men in the United States. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequences. Two common epigenetic mechanisms, DNA methylation and histone modification, have demonstrated critical roles in prostate cancer growth and metastasis. DNA hypermethylation of cytosine-guanine (CpG) rich sequence islands within gene promoter regions is widespread during neoplastic transformation of prostate cells, suggesting that treatment-induced restoration of a "normal" epigenome could be clinically beneficial. Histone modification leads to altered tumor gene function by changing chromosome structure and the level of gene transcription. The reversibility of epigenetic aberrations and restoration of tumor suppression gene function have made them attractive targets for prostate cancer treatment with modulators that demethylate DNA and inhibit histone deacetylases.

  2. Key papers in prostate cancer.

    Science.gov (United States)

    Rodney, Simon; Shah, Taimur Tariq; Patel, Hitendra R H; Arya, Manit

    2014-11-01

    Prostate cancer is the most common cancer and second leading cause of death in men. The evidence base for the diagnosis and treatment of prostate cancer is continually changing. We aim to review and discuss past and contemporary papers on these topics to provoke debate and highlight key dilemmas faced by the urological community. We review key papers on prostate-specific antigen screening, radical prostatectomy versus surveillance strategies, targeted therapies, timing of radiotherapy and alternative anti-androgen therapeutics. Previously, the majority of patients, irrespective of risk, underwent radical open surgical procedures associated with considerable morbidity and mortality. Evidence is emerging that not all prostate cancers are alike and that low-grade disease can be safely managed by surveillance strategies and localized treatment to the prostate. The question remains as to how to accurately stage the disease and ultimately choose which treatment pathway to follow.

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

    Science.gov (United States)

    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.

  4. Exploiting Epigenetic Alterations in Prostate Cancer.

    Science.gov (United States)

    Baumgart, Simon J; Haendler, Bernard

    2017-05-09

    Prostate cancer affects an increasing number of men worldwide and is a leading cause of cancer-associated deaths. Beside genetic mutations, many epigenetic alterations including DNA and histone modifications have been identified in clinical prostate tumor samples. They have been linked to aberrant activity of enzymes and reader proteins involved in these epigenetic processes, leading to the search for dedicated inhibitory compounds. In the wake of encouraging anti-tumor efficacy results in preclinical models, epigenetic modulators addressing different targets are now being tested in prostate cancer patients. In addition, the assessment of microRNAs as stratification biomarkers, and early clinical trials evaluating suppressor microRNAs as potential prostate cancer treatment are being discussed.

  5. Exploiting Epigenetic Alterations in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Simon J. Baumgart

    2017-05-01

    Full Text Available Prostate cancer affects an increasing number of men worldwide and is a leading cause of cancer-associated deaths. Beside genetic mutations, many epigenetic alterations including DNA and histone modifications have been identified in clinical prostate tumor samples. They have been linked to aberrant activity of enzymes and reader proteins involved in these epigenetic processes, leading to the search for dedicated inhibitory compounds. In the wake of encouraging anti-tumor efficacy results in preclinical models, epigenetic modulators addressing different targets are now being tested in prostate cancer patients. In addition, the assessment of microRNAs as stratification biomarkers, and early clinical trials evaluating suppressor microRNAs as potential prostate cancer treatment are being discussed.

  6. Epigenetics in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Costantine Albany

    2011-01-01

    Full Text Available Prostate cancer (PC is the most commonly diagnosed nonskin malignancy and the second most common cause of cancer death among men in the United States. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequences. Two common epigenetic mechanisms, DNA methylation and histone modification, have demonstrated critical roles in prostate cancer growth and metastasis. DNA hypermethylation of cytosine-guanine (CpG rich sequence islands within gene promoter regions is widespread during neoplastic transformation of prostate cells, suggesting that treatment-induced restoration of a “normal” epigenome could be clinically beneficial. Histone modification leads to altered tumor gene function by changing chromosome structure and the level of gene transcription. The reversibility of epigenetic aberrations and restoration of tumor suppression gene function have made them attractive targets for prostate cancer treatment with modulators that demethylate DNA and inhibit histone deacetylases.

  7. Multiparametric MRI in the detection of clinically significant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Futterer, Jurgen J. [Dept. of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen (Netherlands)

    2017-08-01

    Prostate cancer is the most common cancer among men aged 50 years and older in developed countries and the third leading cause of cancer-related death in men. Multiparametric prostate MR imaging is currently the most accurate imaging modality to detect, localize, and stage prostate cancer. The role of multi-parametric MR imaging in the detection of clinically significant prostate cancer are discussed. In addition, insights are provided in imaging techniques, protocol, and interpretation.

  8. Prostate cancer burden in Central and South America.

    Science.gov (United States)

    Sierra, Mónica S; Soerjomataram, Isabelle; Forman, David

    2016-09-01

    The incidence of prostate cancer has increased in Central and South America (CSA) in the last few decades. We describe the geographical patterns and trends of prostate cancer in CSA. We obtained regional and national-level cancer incidence data from 48 population-based registries in 13 countries and nation-wide cancer deaths from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence (ASR) and mortality (ASMR) rates per 100,000 person-years for 2003-2007 and the estimated annual percent change (EAPC) to describe time trends. Prostate cancer was the most common cancer diagnosis and one of the leading causes of cancer deaths among males in most CSA countries. From 2003-2007, ASRs varied between countries (6-fold) and within countries (Brazil: 3-6-fold). French Guyana (147.1) and Brazil (91.4) had the highest ASRs whereas Mexico (28.9) and Cuba (24.3) had the lowest. ASMRs varied by 4-fold. Belize, Uruguay and Cuba (24.1-28.9) had the highest ASMRs while Peru, Nicaragua, and El Salvador (6.8-9.7) had the lowest. In Argentina, Brazil, Chile and Costa Rica prostate cancer incidence increased by 2.8-4.8% annually whereas mortality remained stable between 1997 and 2008. The geographic and temporal variation of prostate cancer rates observed in CSA may in part reflect differences in diagnostic and registration practices, healthcare access, treatment and death certification, and public awareness. The incidence of prostate cancer is expected to increase given recent early detection activities and increased public awareness; however, the impact of these factors on mortality remains to be elucidated. Copyright © 2016 International Agency for Research on Cancer. Published by Elsevier Ltd.. All rights reserved.

  9. Interleukin-30: A novel microenvironmental hallmark of prostate cancer progression.

    Science.gov (United States)

    Di Carlo, Emma

    2014-01-01

    Metastatic prostate cancer is a leading cause of cancer-related death in men worldwide. We have recently discovered that IL-30 shapes the microenvironment of prostate cancer and tumor-draining lymph nodes to favor tumor progression. IL-30 supports tumor growth in vitro, and IL-30 expression in prostate cancer patients is associated with high tumor grade and metastatic stage of disease. Thus, IL-30 may constitute a valuable target for modern therapeutic approaches to hamper prostate cancer progression.

  10. The Role of MRI in Prostate Cancer Active Surveillance

    Directory of Open Access Journals (Sweden)

    Linda M. Johnson

    2014-01-01

    Full Text Available Prostate cancer is the most common cancer diagnosis in American men, excluding skin cancer. The clinical behavior of prostate cancer varies from low-grade, slow growing tumors to high-grade aggressive tumors that may ultimately progress to metastases and cause death. Given the high incidence of men diagnosed with prostate cancer, conservative treatment strategies such as active surveillance are critical in the management of prostate cancer to reduce therapeutic complications of radiation therapy or radical prostatectomy. In this review, we will review the role of multiparametric MRI in the selection and follow-up of patients on active surveillance.

  11. Low-dose irradiation for controlling prostate cancer

    International Nuclear Information System (INIS)

    Cuttler, J.M.

    2003-01-01

    Prostate cancer is the second most commonly diagnosed cancer among North American men and the second leading cause of death in those aged 65 and over. The American Cancer Society recommends testing those over age 50 who are expected to live at least 10 years, even though the ability of early detection to decrease prostate cancer mortality has not been demonstrated. So controversy exists about the appropriateness of screening because of the considerable economic and social burden of diagnosing and treating prostate cancer, coupled with the projected large increase in the number of new cases as the population ages. This very important public health issue could be addressed at low cost by total-body low-dose irradiation therapy to stimulate the patient's own defences to prevent and control most cancers, including prostate cancer, with no symptomatic side effects. (author)

  12. Prostate cancer in South Africa: pathology based national cancer registry data (1986-2006) and mortality rates (1997-2009).

    Science.gov (United States)

    Babb, Chantal; Urban, Margaret; Kielkowski, Danuta; Kellett, Patricia

    2014-01-01

    Prostate cancer is one of the most common male cancers globally; however little is known about prostate cancer in Africa. Incidence data for prostate cancer in South Africa (SA) from the pathology based National Cancer Registry (1986-2006) and data on mortality (1997-2009) from Statistics SA were analysed. World standard population denominators were used to calculate age specific incidence and mortality rates (ASIR and ASMR) using the direct method. Prostate cancer was the most common male cancer in all SA population groups (excluding basal cell carcinoma). There are large disparities in the ASIR between black, white, coloured, and Asian/Indian populations: 19, 65, 46, and 19 per 100 000, respectively, and ASMR was 11, 7, 52, and 6 per 100 000, respectively. Prostate cancer was the second leading cause of cancer death, accounting for around 13% of male deaths from a cancer. The average age at diagnosis was 68 years and 74 years at death. For SA the ASIR increased from 16.8 in 1986 to 30.8 in 2006, while the ASMR increased from 12.3 in 1997 to 16.7 in 2009. There has been a steady increase of incidence and mortality from prostate cancer in SA.

  13. Unemployment and prostate cancer mortality in the OECD, 1990-2009.

    Science.gov (United States)

    Maruthappu, Mahiben; Watkins, Johnathan; Taylor, Abigail; Williams, Callum; Ali, Raghib; Zeltner, Thomas; Atun, Rifat

    2015-01-01

    The global economic downturn has been associated with increased unemployment in many countries. Insights into the impact of unemployment on specific health conditions remain limited. We determined the association between unemployment and prostate cancer mortality in members of the Organisation for Economic Co-operation and Development (OECD). We used multivariate regression analysis to assess the association between changes in unemployment and prostate cancer mortality in OECD member states between 1990 and 2009. Country-specific differences in healthcare infrastructure, population structure, and population size were controlled for and lag analyses conducted. Several robustness checks were also performed. Time trend analyses were used to predict the number of excess deaths from prostate cancer following the 2008 global recession. Between 1990 and 2009, a 1% rise in unemployment was associated with an increase in prostate cancer mortality. Lag analysis showed a continued increase in mortality years after unemployment rises. The association between unemployment and prostate cancer mortality remained significant in robustness checks with 46 controls. Eight of the 21 OECD countries for which a time trend analysis was conducted, exhibited an estimated excess of prostate cancer deaths in at least one of 2008, 2009, or 2010, based on 2000-2007 trends. Rises in unemployment are associated with significant increases in prostate cancer mortality. Initiatives that bolster employment may help to minimise prostate cancer mortality during times of economic hardship.

  14. Fibroblast Growth Factor Receptor-4 and Prostate Cancer Progression

    Science.gov (United States)

    2007-10-01

    difference between the two FGFR-4 variants? Achondroplasia ( dwarfism ) is caused by a similar mutation in FGFR-3 (Gly380 to Arg380). Increased FGFR-3...US men, with approximately 230,000 new cases and 29,000 deaths in 2004 [1]. Prostate cancer deaths are a result of metastatic disease and treatment of...such metastatic disease is one of the major therapeutic challenges in prostate cancer treatment . Many studies have been focused on identification of

  15. Future of bisphosphonates and denosumab for men with advanced prostate cancer

    International Nuclear Information System (INIS)

    Iranikhah, Maryam; Stricker, Steve; Freeman, Maisha Kelly

    2014-01-01

    Prostate cancer is the most common cancer occurring in American men of all races. It is also the second leading cause of cancer death among men in the USA. Bone metastasis is a frequent occurrence in men with advanced prostate cancer, with skeletal-related events being a common complication and having negative consequences, leading to severe pain, increased health care costs, increased risk of death, and decreased quality of life for patients. Bone loss can also result from antiandrogen therapy, which can further contribute to skeletal-related events. Treatment with antiresorptive agents bisphosphonates, and the newly approved denosumab, a receptor activator of nuclear factor kappa-B ligand (RANK-L) inhibitor, has been shown to reduce the risk of skeletal-related complications and prevent treatment-induced bone loss in patients with advanced prostate cancer. This review discusses the role of antiresorptive agents bisphosphonates and RANK-L inhibitor in the current treatment of advanced prostate cancer by examining the primary literature and also focuses on the likely role of the bisphosphonates in the treatment of advanced prostate cancer in the future

  16. Docetaxel-induced prostate cancer cell death involves concomitant activation of caspase and lysosomal pathways and is attenuated by LEDGF/p75

    Directory of Open Access Journals (Sweden)

    Leoh Lai

    2009-08-01

    Full Text Available Abstract Background Hormone-refractory prostate cancer (HRPC is characterized by poor response to chemotherapy and high mortality, particularly among African American men when compared to other racial/ethnic groups. It is generally accepted that docetaxel, the standard of care for chemotherapy of HRPC, primarily exerts tumor cell death by inducing mitotic catastrophe and caspase-dependent apoptosis following inhibition of microtubule depolymerization. However, there is a gap in our knowledge of mechanistic events underlying docetaxel-induced caspase-independent cell death, and the genes that antagonize this process. This knowledge is important for circumventing HRPC chemoresistance and reducing disparities in prostate cancer mortality. Results We investigated mechanistic events associated with docetaxel-induced death in HRPC cell lines using various approaches that distinguish caspase-dependent from caspase-independent cell death. Docetaxel induced both mitotic catastrophe and caspase-dependent apoptosis at various concentrations. However, caspase activity was not essential for docetaxel-induced cytotoxicity since cell death associated with lysosomal membrane permeabilization still occurred in the presence of caspase inhibitors. Partial inhibition of docetaxel-induced cytotoxicity was observed after inhibition of cathepsin B, but not inhibition of cathepsins D and L, suggesting that docetaxel induces caspase-independent, lysosomal cell death. Simultaneous inhibition of caspases and cathepsin B dramatically reduced docetaxel-induced cell death. Ectopic expression of lens epithelium-derived growth factor p75 (LEDGF/p75, a stress survival autoantigen and transcription co-activator, attenuated docetaxel-induced lysosomal destabilization and cell death. Interestingly, LEDGF/p75 overexpression did not protect cells against DTX-induced mitotic catastrophe, and against apoptosis induced by tumor necrosis factor related apoptosis inducing ligand (TRAIL

  17. Prostate Cancer in South Africa: Pathology Based National Cancer Registry Data (1986–2006 and Mortality Rates (1997–2009

    Directory of Open Access Journals (Sweden)

    Chantal Babb

    2014-01-01

    Full Text Available Prostate cancer is one of the most common male cancers globally; however little is known about prostate cancer in Africa. Incidence data for prostate cancer in South Africa (SA from the pathology based National Cancer Registry (1986–2006 and data on mortality (1997–2009 from Statistics SA were analysed. World standard population denominators were used to calculate age specific incidence and mortality rates (ASIR and ASMR using the direct method. Prostate cancer was the most common male cancer in all SA population groups (excluding basal cell carcinoma. There are large disparities in the ASIR between black, white, coloured, and Asian/Indian populations: 19, 65, 46, and 19 per 100 000, respectively, and ASMR was 11, 7, 52, and 6 per 100 000, respectively. Prostate cancer was the second leading cause of cancer death, accounting for around 13% of male deaths from a cancer. The average age at diagnosis was 68 years and 74 years at death. For SA the ASIR increased from 16.8 in 1986 to 30.8 in 2006, while the ASMR increased from 12.3 in 1997 to 16.7 in 2009. There has been a steady increase of incidence and mortality from prostate cancer in SA.

  18. Enzalutamide in metastatic prostate cancer before chemotherapy

    DEFF Research Database (Denmark)

    Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana E

    2014-01-01

    BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have...... the most common clinically relevant adverse events associated with enzalutamide treatment. CONCLUSIONS: Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer. (Funded by Medivation and Astellas...... skeletal-related event (hazard ratio, 0.72), a complete or partial soft-tissue response (59% vs. 5%), the time until prostate-specific antigen (PSA) progression (hazard ratio, 0.17), and a rate of decline of at least 50% in PSA (78% vs. 3%) (P

  19. 15-year followup of a population based prostate cancer screening study.

    Science.gov (United States)

    Kjellman, Anders; Akre, Olof; Norming, Ulf; Törnblom, Magnus; Gustafsson, Ove

    2009-04-01

    We evaluated long-term survival in attendees and nonattendees of a 1-time screening for prostate cancer. A total of 2,400 men 55 to 70 years old in 1988 were randomly selected and invited to a screening for prostate cancer. Of the invited men 1,782 (74%) attended. Screening attendees were examined with digital rectal examination, transrectal ultrasound and prostate specific antigen analysis. When cancer was suspected, prostate biopsies were taken. A total of 65 men with prostate cancer were detected by this procedure. The entire source population comprising 27,204 men, including 618 nonattendees (26%), was followed for prostate cancer diagnosis and survival for 15 years. Incidence rate ratios were calculated using Poisson regression models. We found no effect of this screening procedure on the risk of death from prostate cancer and other causes of death (incidence rate ratio 1.10, 95% CI 0.83-1.46 and 0.98, 95% CI 0.92-1.05, respectively) when comparing all invited men with the source population. However, attending the screening program was associated with a significantly decreased risk of death from causes other than prostate cancer (vs source population incidence rate ratio 0.82, 95% CI 0.76-0.90). In contrast, the corresponding incidence rate ratio in nonattendees was 1.53 (95% CI 1.37-1.71). We found no evidence of a beneficial effect of this specific screening procedure but strong evidence of a difference in overall survival in screening attendees and nonattendees. These findings should be considered when interpreting previous and upcoming studies of the effect of screening programs.

  20. Current Stem Cell Biomarkers and Their Functional Mechanisms in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Kaile Zhang

    2016-07-01

    Full Text Available Currently there is little effective treatment available for castration resistant prostate cancer, which is responsible for the majority of prostate cancer related deaths. Emerging evidence suggested that cancer stem cells might play an important role in resistance to traditional cancer therapies, and the studies of cancer stem cells (including specific isolation and targeting on those cells might benefit the discovery of novel treatment of prostate cancer, especially castration resistant disease. In this review, we summarized major biomarkers for prostate cancer stem cells, as well as their functional mechanisms and potential application in clinical diagnosis and treatment of patients.

  1. Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer.

    Science.gov (United States)

    Ebot, Ericka M; Gerke, Travis; Labbé, David P; Sinnott, Jennifer A; Zadra, Giorgia; Rider, Jennifer R; Tyekucheva, Svitlana; Wilson, Kathryn M; Kelly, Rachel S; Shui, Irene M; Loda, Massimo; Kantoff, Philip W; Finn, Stephen; Vander Heiden, Matthew G; Brown, Myles; Giovannucci, Edward L; Mucci, Lorelei A

    2017-11-01

    Obese men are at higher risk of advanced prostate cancer and cancer-specific mortality; however, the biology underlying this association remains unclear. This study examined gene expression profiles of prostate tissue to identify biological processes differentially expressed by obesity status and lethal prostate cancer. Gene expression profiling was performed on tumor (n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2 prospective cohorts who had been diagnosed with prostate cancer from 1982 to 2005. Body mass index (BMI) was calculated from the questionnaire immediately preceding cancer diagnosis. Men were followed for metastases or prostate cancer-specific death (lethal disease) through 2011. Gene Ontology biological processes differentially expressed by BMI were identified using gene set enrichment analysis. Pathway scores were computed by averaging the signal intensities of member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with logistic regression. Among 402 men, 48% were healthy weight, 31% were overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched in tumor tissue, but not normal tissue, of very overweight/obese men versus healthy-weight men; 5 of these were related to chromatin modification and remodeling (false-discovery rate 7, 41% vs 17%; P = 2 × 10 -4 ) and an increased risk of lethal disease that was independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25). This study improves our understanding of the biology of aggressive prostate cancer and identifies a potential mechanistic link between obesity and prostate cancer death that warrants further study. Cancer 2017;123:4130-4138. © 2017 American Cancer Society. © 2017 American Cancer Society.

  2. Prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, G.P.; Kuss, R., Khoury, S.; Chatelain, C.; Denis, L.

    1987-01-01

    This book contains over 70 selections. Some of the titles are: Place of the Computed Tomography in the Staging of Prostatic Cancer; Magnetic Resonance Imaging (MRI) in Staging of the Prostatic Cancer; Magnetic Resonance Imaging of the Prostate; Long-Term Results in Radiotherapy of Prostatic Cancer; Interstitial Irradiation Using I-125 Seeds; and Treatment of Cancer of the Prostate by Use of Physiotherapy: Long-Term Results.

  3. Prostate cancer

    International Nuclear Information System (INIS)

    Murphy, G.P.; Kuss, R.; Khoury, S.; Chatelain, C.; Denis, L.

    1987-01-01

    This book contains over 70 selections. Some of the titles are: Place of the Computed Tomography in the Staging of Prostatic Cancer; Magnetic Resonance Imaging (MRI) in Staging of the Prostatic Cancer; Magnetic Resonance Imaging of the Prostate; Long-Term Results in Radiotherapy of Prostatic Cancer; Interstitial Irradiation Using I-125 Seeds; and Treatment of Cancer of the Prostate by Use of Physiotherapy: Long-Term Results

  4. Progress in Gene Therapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Ahmed, Kamran A.; Davis, Brian J.; Wilson, Torrence M.; Wiseman, Gregory A.; Federspiel, Mark J.; Morris, John C.

    2012-01-01

    Gene therapy has held promise to correct various disease processes. Prostate cancer represents the second leading cause of cancer death in American men. A number of clinical trials involving gene therapy for the treatment of prostate cancer have been reported. The ability to efficiently transduce tumors with effective levels of therapeutic genes has been identified as a fundamental barrier to effective cancer gene therapy. The approach utilizing gene therapy in prostate cancer patients at our institution attempts to address this deficiency. The sodium-iodide symporter (NIS) is responsible for the ability of the thyroid gland to transport and concentrate iodide. The characteristics of the NIS gene suggest that it could represent an ideal therapeutic gene for cancer therapy. Published results from Mayo Clinic researchers have indicated several important successes with the use of the NIS gene and prostate gene therapy. Studies have demonstrated that transfer of the human NIS gene into prostate cancer using adenovirus vectors in vitro and in vivo results in efficient uptake of radioactive iodine and significant tumor growth delay with prolongation of survival. Preclinical successes have culminated in the opening of a phase I trial for patients with advanced prostate disease which is currently accruing patients. Further study will reveal the clinical promise of NIS gene therapy in the treatment of prostate as well as other malignancies.

  5. Progress in Gene Therapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Kamran A.; Davis, Brian J. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Wilson, Torrence M. [Department of Urology, Mayo Clinic, Rochester, MN (United States); Wiseman, Gregory A. [Division of Nuclear Medicine, Mayo Clinic, Rochester, MN (United States); Federspiel, Mark J. [Department of Molecular Medicine, Mayo Clinic, Rochester, MN (United States); Morris, John C., E-mail: davis.brian@mayo.edu [Division of Endocrinology, Mayo Clinic, Rochester, MN (United States)

    2012-11-19

    Gene therapy has held promise to correct various disease processes. Prostate cancer represents the second leading cause of cancer death in American men. A number of clinical trials involving gene therapy for the treatment of prostate cancer have been reported. The ability to efficiently transduce tumors with effective levels of therapeutic genes has been identified as a fundamental barrier to effective cancer gene therapy. The approach utilizing gene therapy in prostate cancer patients at our institution attempts to address this deficiency. The sodium-iodide symporter (NIS) is responsible for the ability of the thyroid gland to transport and concentrate iodide. The characteristics of the NIS gene suggest that it could represent an ideal therapeutic gene for cancer therapy. Published results from Mayo Clinic researchers have indicated several important successes with the use of the NIS gene and prostate gene therapy. Studies have demonstrated that transfer of the human NIS gene into prostate cancer using adenovirus vectors in vitro and in vivo results in efficient uptake of radioactive iodine and significant tumor growth delay with prolongation of survival. Preclinical successes have culminated in the opening of a phase I trial for patients with advanced prostate disease which is currently accruing patients. Further study will reveal the clinical promise of NIS gene therapy in the treatment of prostate as well as other malignancies.

  6. Clinical utility of the percentage of positive prostate biopsies in predicting prostate cancer-specific and overall survival after radiotherapy for patients with localized prostate cancer

    International Nuclear Information System (INIS)

    D'Amico, Anthony V.; Keshaviah, Aparna; Manola, Judith; Cote, Kerri; Loffredo, Marian; Iskrzytzky, Olga; Renshaw, Andrew A.

    2002-01-01

    Purpose: To determine whether the percentage of positive prostate biopsies provides clinically relevant information to a previously established risk stratification system with respect to the end points of prostate cancer-specific survival (PCSS) and overall survival after radiotherapy for patients with clinically localized prostate cancer. Methods and Materials: A Cox regression multivariable analysis was used to evaluate the ability of the percentage of positive prostate biopsies to predict PCSS and overall survival for 381 men who underwent radiotherapy for localized prostate cancer during the prostate-specific antigen era. Results: At a median follow-up of 4.3 years (range 0.8-13.3), the presence of ≤50% positive biopsies vs. >50% positive biopsies provided a clinically relevant stratification of the 7-year estimates of PCSS (100% vs. 57%, p=0.004) in intermediate-risk patients. Moreover, all patients could be stratified into a minimal or high-risk cohort on the basis of the 10-year estimates of PCSS (100% vs. 55%, p 50%] intermediate-risk + high-risk) cohort for prostate cancer-specific death after conventional dose radiotherapy. Additional follow-up and independent validation are needed to confirm these findings

  7. Mortality results from the Göteborg Randomised Prostate Cancer Screening Trial

    Science.gov (United States)

    Hugosson, Jonas; Carlsson, Sigrid; Aus, Gunnar; Bergdahl, Svante; Khatami, Ali; Lodding, Pär; Pihl, Carl-Gustaf; Stranne, Johan; Holmberg, Erik; Lilja, Hans

    2013-01-01

    Summary Background Prostate cancer is one of the leading causes of death from malignant disease among men in the Western world. One strategy to decrease the risk of dying from this disease is screening with Prostate-Specific Antigen (PSA); however, the extent of benefit and harm with such screening is under continuous debate. Methods In December 1994, 20 000 men born 1930 to 1944, randomly sampled from the Population Register, were computer randomised in a 1:1 ratio to a screening group invited for biennial PSA testing or to a control group not invited. In each arm, 48 men were excluded from analysis due to either death or emigration before randomization date or prevalent prostate cancer. The primary endpoint was prostate cancer specific mortality analyzed according to the intention-to-screen principle. Men in the screening group were invited up to the upper age limit (median 69, range 67–71 years) and only men with elevated PSA were offered additional tests such as digital rectal examination and prostate biopsies. The study is still ongoing inviting men who have not yet reached the upper age limit. This is the first planned report on cumulative prostate cancer incidence and mortality calculated up to Dec 31 2008. This study is registered [as an International Standard Randomised Controlled Trial], number [ISRCTN49127736]. Findings Among men randomised to screening 7578/9952 (76%) attended at least once (attendees). During a median follow-up of 14 years, 1138 men in the screening group and 718 in the control group were diagnosed with prostate cancer resulting in a cumulative incidence of prostate cancer of 12.7% in the screening arm and 8.2% in the control arm (hazard ratio 1.64; 95% confidence interval [CI] 1.50–1.80; pattendees compared to the control group was 0.44 (95% CI 0.28–0.68; p=0.0002). Overall, 293 men needed to be invited for screening and 12 to be diagnosed to prevent one prostate cancer death. Interpretation The benefit of prostate cancer

  8. Causes of death among cancer patients.

    Science.gov (United States)

    Zaorsky, N G; Churilla, T M; Egleston, B L; Fisher, S G; Ridge, J A; Horwitz, E M; Meyer, J E

    2017-02-01

    The purpose of our study was to characterize the causes of death among cancer patients as a function of objectives: (i) calendar year, (ii) patient age, and (iii) time after diagnosis. US death certificate data in Surveillance, Epidemiology, and End Results Stat 8.2.1 were used to categorize cancer patient death as being due to index-cancer, nonindex-cancer, and noncancer cause from 1973 to 2012. In addition, data were characterized with standardized mortality ratios (SMRs), which provide the relative risk of death compared with all persons. The greatest relative decrease in index-cancer death (generally from > 60% to deaths were stable (typically >40%) among patients with cancers of the liver, pancreas, esophagus, and lung, and brain. Noncancer causes of death were highest in patients with cancers of the colorectum, bladder, kidney, endometrium, breast, prostate, testis; >40% of deaths from heart disease. The highest SMRs were from nonbacterial infections, particularly among 1,000 for lymphomas, P death from index- and nonindex-cancers varies widely among primary sites. Risk of noncancer deaths now surpasses that of cancer deaths, particularly for young patients in the year after diagnosis. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Current state of prostate cancer treatment in Jamaica.

    Science.gov (United States)

    Morrison, Belinda F; Aiken, William D; Mayhew, Richard

    2014-01-01

    Prostate cancer is the commonest cancer in Jamaica as well as the leading cause of cancer-related deaths. One report suggested that Jamaica has the highest incidence rate of prostate cancer in the world, with an age-standardised rate of 304/100,000 per year. The Caribbean region is reported to have the highest mortality rate of prostate cancer worldwide. Prostate cancer accounts for a large portion of the clinical practice for health-care practitioners in Jamaica. The Jamaica Urological Society is a professional body comprising 19 urologists in Jamaica who provide most of the care for men with prostate cancer in collaboration with medical oncologists, radiation oncologists, and a palliative care physician. The health-care system is structured in two tiers in Jamaica: public and private. The urologist-to-patient ratio is high, and this limits adequate urological care. Screening for prostate cancer is not a national policy in Jamaica. However, the Jamaica Urological Society and the Jamaica Cancer Society work synergistically to promote screening as well as to provide patient education for prostate cancer. Adequate treatment for localised prostate cancer is available in Jamaica in the forms of active surveillance, nerve-sparing radical retropubic prostatectomy, external beam radiation, and brachytherapy. However, there is a geographic maldistribution of centres that provide prostate cancer treatment, which leads to treatment delays. Also, there is difficulty in affording some treatment options in the private health-care sectors. Androgen deprivation therapy is available for treatment of locally advanced and metastatic prostate cancer and is subsidised through a programme called the National Health Fund. Second-line hormonal agents and chemotherapeutic agents are available but are costly to most of the population. The infrastructure for treatment of prostate cancer in Jamaica is good, but it requires additional technological advances as well as additional specialist

  10. Pomegranate and Its Components as Alternative Treatment for Prostate Cancer

    Science.gov (United States)

    Wang, Lei; Martins-Green, Manuela

    2014-01-01

    Prostate cancer is the second leading cause of cancer deaths in men in the United States. There is a major need for less toxic but yet effective therapies to treat prostate cancer. Pomegranate fruit from the tree Punica granatum has been used for centuries for medicinal purposes and is described as “nature’s power fruit”. Recent research has shown that pomegranate juice (PJ) and/or pomegranate extracts (PE) significantly inhibit the growth of prostate cancer cells in culture. In preclinical murine models, PJ and/or PE inhibit growth and angiogenesis of prostate tumors. More recently, we have shown that three components of PJ, luteolin, ellagic acid and punicic acid together, have similar inhibitory effects on prostate cancer growth, angiogenesis and metastasis. Results from clinical trials are also promising. PJ and/or PE significantly prolonged the prostate specific antigen (PSA) doubling time in patients with prostate cancer. In this review we discuss data on the effects of PJ and PE on prostate cancer. We also discuss the effects of specific components of the pomegranate fruit and how they have been used to study the mechanisms involved in prostate cancer progression and their potential to be used in deterring prostate cancer metastasis. PMID:25158234

  11. ROS-mediated apoptotic cell death in prostate cancer LNCaP cells induced by biosurfactant stabilized CdS quantum dots.

    Science.gov (United States)

    Singh, Braj R; Singh, Brahma N; Khan, W; Singh, H B; Naqvi, A H

    2012-08-01

    Cadmium sulfide (CdS) quantum dots (QDs) have raised great attention because of their superior optical properties and wide utilization in biological and biomedical studies. However, little is known about the cell death mechanisms of CdS QDs in human cancer cells. This study was designed to investigate the possible mechanisms of apoptosis induced by biosurfactant stabilized CdS QDs (denoted as "bsCdS QDs") in human prostate cancer LNCaP cells. It was also noteworthy that apoptosis correlated with reactive oxygen species (ROS) production, mitochondrial damage, oxidative stress and chromatin condensation in a dose- and time-dependent manner. Results also showed involvement of caspases, Bcl-2 family proteins, heat shock protein 70, and a cell-cycle checkpoint protein p53 in apoptosis induction by bsCdS QDs in LNCaP cells. Moreover, pro-apoptotic protein Bax was upregulated and the anti-apoptotic proteins, survivin and NF-κB were downregulated in bsCdS QDs exposed cells. Protection of N-acetyl cysteine (NAC) against ROS clearly suggested the implication of ROS in hyper-activation of apoptosis and cell death. It is encouraging to conclude that biologically stabilized CdS QDs bear the potential of its applications in biomedicine, such as tumor therapy specifically by inducing caspase-dependent apoptotic cell death of human prostate cancer LNCaP cells. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  12. All-Cause Mortality for Life Insurance Applicants with a History of Prostate Cancer.

    Science.gov (United States)

    Freitas, Stephen A; MacKenzie, Ross; Wylde, David N; Roudebush, Bradley T; Bergstrom, Richard L; Holowaty, J Carl; Beckman, Margaret; Rigatti, Steven J; Gill, Stacy

    2017-01-01

    - To determine the all-cause mortality of life insurance applicants diagnosed with prostate cancer currently or at some time in the past. - Prostate cancer is common and a frequent cause of cancer death. Both the frequency of prostate cancer in men and its propensity for causing premature mortality require insurance company medical directors and underwriters to have a good understanding of prostate cancer-related mortality trends, patterns, and outcomes in the insured population. - Life insurance applicants with reported prostate cancer were extracted from data covering United States residents between November 2007 and November 2014. Information about these applicants was matched to the Social Security Death Master (SSDMF) file for deaths occurring from 2007 to 2011 and to another commercially available death source file (Other Death Source, ODS) for deaths occurring from 2007 to 2014 to determine vital status. Actual to Expected (A/E) mortality ratios were calculated using the Society of Actuaries 2015 Valuation Basic Table (2015VBT), select and ultimate table (age last birthday) and the 2013 US population as expected mortality ratios. All expected bases were not smoker distinct. - The study covered applicants between the ages of 45 and 75 and had approximately 405,000 person-years of exposure. Older aged applicants had a lower mortality ratio than those who were younger. Applicants 45 to 54 had the highest mortality ratios in the first year after diagnosis which steadily decreased in years 6 to 10 with an increase in the mortality ratio for those over 10 years from diagnosis. Relative mortality rate was close to unity for those with localized cancer across all age groups. The mortality ratio was 2 to 4 times greater for those with cancer in 1 positive node, and much greater with 3 positive nodes. For each time-from-diagnosis category, the relative mortality ratios compared to age were highest in the 45-54 age group. The A/E mortality ratios based on the 2015VBT

  13. The epigenetic promise for prostate cancer diagnosis.

    Science.gov (United States)

    Van Neste, Leander; Herman, James G; Otto, Gaëtan; Bigley, Joseph W; Epstein, Jonathan I; Van Criekinge, Wim

    2012-08-01

    Prostate cancer is the most common cancer diagnosis in men and a leading cause of death. Improvements in disease management would have a significant impact and could be facilitated by the development of biomarkers, whether for diagnostic, prognostic, or predictive purposes. The blood-based prostate biomarker PSA has been part of clinical practice for over two decades, although it is surrounded by controversy. While debates of usefulness are ongoing, alternatives should be explored. Particularly with recent recommendations against routine PSA-testing, the time is ripe to explore promising biomarkers to yield a more efficient and accurate screening for detection and management of prostate cancer. Epigenetic changes, more specifically DNA methylation, are amongst the most common alterations in human cancer. These changes are associated with transcriptional silencing of genes, leading to an altered cellular biology. One gene in particular, GSTP1, has been widely studied in prostate cancer. Therefore a meta-analysis has been conducted to examine the role of this and other genes and the potential contribution to prostate cancer management and screening refinement. More than 30 independent, peer reviewed studies have reported a consistently high sensitivity and specificity of GSTP1 hypermethylation in prostatectomy or biopsy tissue. The meta-analysis combined and compared these results. GSTP1 methylation detection can serve an important role in prostate cancer managment. The meta-analysis clearly confirmed a link between tissue DNA hypermethylation of this and other genes and prostate cancer. Detection of DNA methylation in genes, including GSTP1, could serve an important role in clinical practice. Copyright © 2011 Wiley Periodicals, Inc.

  14. Mortality results from the Göteborg randomised population-based prostate-cancer screening trial.

    Science.gov (United States)

    Hugosson, Jonas; Carlsson, Sigrid; Aus, Gunnar; Bergdahl, Svante; Khatami, Ali; Lodding, Pär; Pihl, Carl-Gustaf; Stranne, Johan; Holmberg, Erik; Lilja, Hans

    2010-08-01

    Prostate cancer is one of the leading causes of death from malignant disease among men in the developed world. One strategy to decrease the risk of death from this disease is screening with prostate-specific antigen (PSA); however, the extent of benefit and harm with such screening is under continuous debate. In December, 1994, 20,000 men born between 1930 and 1944, randomly sampled from the population register, were randomised by computer in a 1:1 ratio to either a screening group invited for PSA testing every 2 years (n=10,000) or to a control group not invited (n=10,000). Men in the screening group were invited up to the upper age limit (median 69, range 67-71 years) and only men with raised PSA concentrations were offered additional tests such as digital rectal examination and prostate biopsies. The primary endpoint was prostate-cancer specific mortality, analysed according to the intention-to-screen principle. The study is ongoing, with men who have not reached the upper age limit invited for PSA testing. This is the first planned report on cumulative prostate-cancer incidence and mortality calculated up to Dec 31, 2008. This study is registered as an International Standard Randomised Controlled Trial ISRCTN54449243. In each group, 48 men were excluded from the analysis because of death or emigration before the randomisation date, or prevalent prostate cancer. In men randomised to screening, 7578 (76%) of 9952 attended at least once. During a median follow-up of 14 years, 1138 men in the screening group and 718 in the control group were diagnosed with prostate cancer, resulting in a cumulative prostate-cancer incidence of 12.7% in the screening group and 8.2% in the control group (hazard ratio 1.64; 95% CI 1.50-1.80; pattendees compared with the control group was 0.44 (95% CI 0.28-0.68; p=0.0002). Overall, 293 (95% CI 177-799) men needed to be invited for screening and 12 to be diagnosed to prevent one prostate cancer death. This study shows that prostate

  15. Genetic and Epigenetic Silencing of the AS3 Proliferative rrest Gene in Prostate Cancer

    National Research Council Canada - National Science Library

    Geck, Peter

    2005-01-01

    Prostate cancer is the second leading cause of death among American men. The present proposal extends the molecular progress in prostate cancer into clinical practice by developing innovative markers...

  16. Genetic and Epigenetic Silencing of the AS3 Proliferative Arrest Gene in Prostate Cancer

    National Research Council Canada - National Science Library

    Geck, Peter

    2004-01-01

    Prostate cancer is the second leading cause of death among American men. The present proposal extends the molecular progress in prostate cancer into clinical practice by developing innovative markers...

  17. Functional roles for Rad9 in prostate cancer

    International Nuclear Information System (INIS)

    Lieberman, H.B.; Broustas, C.G.

    2012-01-01

    The goal of this work is to understand the mechanistic relationship between high levels of Rad9 protein and prostate cancer. The study is based on several findings suggesting a role for Rad9 in this disease. Rad9 has all the hallmark features of an oncogene or tumor suppressor. It regulates genomic stability, multiple cell cycle checkpoints, apoptosis and DNA repair. In addition, it can transactivate downstream target genes via direct interaction with promoter DNA sequences. We found Rad9 protein levels were very high in prostate cancer cell lines. Furthermore, we examined 52 primary normal prostate and 339 prostate cancer specimens for Rad9 protein by immunohistochemical staining. Statistical significance for Rad9 positive staining versus cancer, and stain intensity versus Stage were tested. We get a p-value of <0.001 when comparing percentage positive by cancer Stage, or stain intensity by cancer Stage. Based on these data, we sought to define the nature of the relationship between Rad9 and prostate cancer. We demonstrate that Rad9 acts as an oncogene in prostate cancer by playing a critical role in tumor formation in a mouse xenograph model. We also show that Rad9 is important for cellular phenotypes essential for metastasis, including tumor cell migration, invasion and resistance to programmed cell death after detachment from extracellular matrix. Therefore, Rad9 is critical for several aspects of prostate tumor progression, and could serve as a novel target for anti-cancer therapy

  18. P53 expression in prostatic cancer: an immunohistochemical study

    International Nuclear Information System (INIS)

    Al-Nuaimy, W.M.; Al-Allaf, L.I.; Alnaimi, H.A.

    2011-01-01

    Prostate cancer is the most common malignancy in men and second leading cause of cancer death in the Western world. P53 alterations are the most frequent genetic changes in human cancers. Mutation of the p53 gene has been implicated in the development of >50% of all human cancer. The current study aims at evaluating the immuno-histochemical expression of p53 protein in patients with cancer of prostate, as prognostic parameter in correlation with other parameters including PSA receptors, and to correlate the results with those of other studies. (authors).

  19. Outcomes following negative prostate biopsy for patients with persistent disease after radiotherapy for prostate cancer

    Directory of Open Access Journals (Sweden)

    Jacob H. Cohen

    2010-02-01

    Full Text Available PURPOSE: When faced with biochemical recurrence after definitive radiotherapy for prostate cancer, clinicians must determine whether the recurrence is local or systemic. Post radiotherapy prostate biopsies to detect persistent local disease are difficult to interpret histopathologically and are subject to sampling error. Our study examines outcomes for patients with a negative prostate biopsy performed for rising prostate-specific antigen (PSA levels after prostate radiation. MATERIALS AND METHODS: We performed a retrospective review of 238 prostate cancer patients with a negative biopsy following definitive radiotherapy. Seventy-five of these patients had biochemical recurrence at the time of biopsy. A negative biopsy was defined as the absence of prostate cancer without radiation-treatment effect in the specimen. RESULTS: Patients underwent biopsy at a mean of 41 months after the completion of radiation. They had a mean PSA of 6. Patients were followed for an average of 63 months. Thirty-two patients (43% developed metastasis, and 11 (15% died of prostate cancer despite a negative post-radiation biopsy. Five of nine patients (56% with sequential biopsies had a positive second biopsy. CONCLUSIONS: Patients with PSA recurrence and a negative post-radiation biopsy have a high chance of persistent local disease, progression, and death from prostate cancer. Furthermore, an initial negative biopsy does not rule-out local recurrence. Patients with biochemical recurrence after radiotherapy for prostate cancer need to be evaluated earlier for local recurrence.

  20. Nerve Growth Factor in Cancer Cell Death and Survival

    International Nuclear Information System (INIS)

    Molloy, Niamh H.; Read, Danielle E.; Gorman, Adrienne M.

    2011-01-01

    One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75 NTR , a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75 NTR . For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75 NTR . This latter signaling through p75 NTR promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75 NTR mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer

  1. Gene therapy for prostate cancer.

    LENUS (Irish Health Repository)

    Tangney, Mark

    2012-01-31

    Cancer remains a leading cause of morbidity and mortality. Despite advances in understanding, detection, and treatment, it accounts for almost one-fourth of all deaths per year in Western countries. Prostate cancer is currently the most commonly diagnosed noncutaneous cancer in men in Europe and the United States, accounting for 15% of all cancers in men. As life expectancy of individuals increases, it is expected that there will also be an increase in the incidence and mortality of prostate cancer. Prostate cancer may be inoperable at initial presentation, unresponsive to chemotherapy and radiotherapy, or recur following appropriate treatment. At the time of presentation, patients may already have metastases in their tissues. Preventing tumor recurrence requires systemic therapy; however, current modalities are limited by toxicity or lack of efficacy. For patients with such metastatic cancers, the development of alternative therapies is essential. Gene therapy is a realistic prospect for the treatment of prostate and other cancers, and involves the delivery of genetic information to the patient to facilitate the production of therapeutic proteins. Therapeutics can act directly (eg, by inducing tumor cells to produce cytotoxic agents) or indirectly by upregulating the immune system to efficiently target tumor cells or by destroying the tumor\\'s vasculature. However, technological difficulties must be addressed before an efficient and safe gene medicine is achieved (primarily by developing a means of delivering genes to the target cells or tissue safely and efficiently). A wealth of research has been carried out over the past 20 years, involving various strategies for the treatment of prostate cancer at preclinical and clinical trial levels. The therapeutic efficacy observed with many of these approaches in patients indicates that these treatment modalities will serve as an important component of urological malignancy treatment in the clinic, either in isolation or

  2. 3-Bromopyruvate induces rapid human prostate cancer cell death by affecting cell energy metabolism, GSH pool and the glyoxalase system.

    Science.gov (United States)

    Valenti, Daniela; Vacca, Rosa A; de Bari, Lidia

    2015-12-01

    3-bromopyruvate (3-BP) is an anti-tumour drug effective on hepatocellular carcinoma and other tumour cell types, which affects both glycolytic and mitochondrial targets, depleting cellular ATP pool. Here we tested 3-BP on human prostate cancer cells showing, differently from other tumour types, efficient ATP production and functional mitochondrial metabolism. We found that 3-BP rapidly induced cultured androgen-insensitive (PC-3) and androgen-responsive (LNCaP) prostate cancer cell death at low concentrations (IC(50) values of 50 and 70 μM, respectively) with a multimodal mechanism of action. In particular, 3-BP-treated PC-3 cells showed a selective, strong reduction of glyceraldeide 3-phosphate dehydrogenase activity, due to the direct interaction of the drug with the enzyme. Moreover, 3-BP strongly impaired both glutamate/malate- and succinate-dependent mitochondrial respiration, membrane potential generation and ATP synthesis, concomitant with the inhibition of respiratory chain complex I, II and ATP synthase activities. The drastic reduction of cellular ATP levels and depletion of GSH pool, associated with significant increase in cell oxidative stress, were found after 3-BP treatment of PC-3 cells. Interestingly, the activity of both glyoxalase I and II, devoted to the elimination of the cytotoxic methylglyoxal, was strongly inhibited by 3-BP. Both N-acetylcysteine and aminoguanidine, GSH precursor and methylglyoxal scavenger, respectively, prevented 3-BP-induced PC-3 cell death, showing that impaired cell antioxidant and detoxifying capacities are crucial events leading to cell death. The provided information on the multi-target cytotoxic action of 3-BP, finally leading to PC-3 cell necrosis, might be useful for future development of 3-BP as a therapeutic option for prostate cancer treatment.

  3. Gene Delivery for Metastatic Prostate Cancer Cells

    National Research Council Canada - National Science Library

    Pang, Shen

    2001-01-01

    .... Enhanced by the bystander effect, the specific expression of the DTA gene causes significant cell death in prostate cancer cell cultures, with very low background cell eradication in control cell lines...

  4. Inuit are protected against prostate cancer

    DEFF Research Database (Denmark)

    Dewailly, Eric; Mulvad, Gert; Pedersen, Henning Sloth

    2003-01-01

    Incidence and mortality rates for prostate cancer are reported to be low among Inuit, but this finding must be additionally supported given the difficulty of obtaining a precise medical diagnosis in the Arctic. We conducted an autopsy study in 1990–1994 among 61 deceased males representative of all...... deaths occurring in Greenland and found only one invasive prostate cancer. Histological data were available for 27 autopsies and revealed no latent carcinoma. Our results suggest that in situ carcinoma is rare among Inuit and that their traditional diet, which is rich in omega-3 polyunsaturated fatty...

  5. Stages of Prostate Cancer

    Science.gov (United States)

    ... Genetics of Prostate Cancer Prostate Cancer Screening Research Prostate Cancer Treatment (PDQ®)–Patient Version General Information About Prostate Cancer Go to Health Professional Version Key Points Prostate ...

  6. Prostate Cancer FAQs

    Science.gov (United States)

    ... Fundraise for PCF: Many vs Cancer Contact Us Prostate Cancer FAQs Top 10 Things You Should Know About ... prostate cancer detected? What are the symptoms of prostate cancer? If the cancer is caught at its earliest ...

  7. Childhood height increases the risk of prostate cancer mortality

    DEFF Research Database (Denmark)

    Aarestrup, J; Gamborg, M; Cook, M B

    2015-01-01

    cancers. Cox proportional hazards regressions were performed. RESULTS: 630 men had prostate cancer recorded as the underlying cause of death. Childhood height at age 13years was positively associated with prostate cancer-specific mortality (hazard ratio [HR]per z-score=1.2, 95% confidence interval [CI]: 1.1-1.3......). Associations were significant at all other childhood ages. Growth analyses showed that height at age 13years had a stronger association with prostate cancer-specific mortality than height at age 7, suggesting the association at age 7 is largely mediated through later childhood height. The tallest boys at age...... 13years had a significantly worse survival, but only when restricted to a diagnosis at years of age (HRz-score of 1=1.7, 95% CI: 1.3-2.4). These associations were significant at all other childhood ages. Childhood BMI was not associated with prostate cancer mortality or survival. CONCLUSION...

  8. Overcoming Drug Resistant Prostate Cancer with APE1/Ref 1 Blockade

    Science.gov (United States)

    2016-10-01

    from prostate specimens removed collaterally from bladder cancer patients undergoing radical cystectomy (cystoprosta- tectomy) as control human specimens...pretreatment with Bacillus Calmette-Guerin as first-line therapy because these patients had presented with muscle invasive bladder cancer . Further, the controls...Krolewski JJ. FLIP-ping out: Death receptor signaling in the prostate. Cancer Biol Ther 2008;7:1171–1179. 21. Shariat SF, Ashfaq R, Roehrborn CG, Slawin

  9. Prostate Cancer

    Science.gov (United States)

    ... 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 ...

  10. Prostate Cancer Symptoms

    Science.gov (United States)

    ... Fundraise for PCF: Many vs Cancer Contact Us Prostate Cancer Symptoms and Signs Prostate Cancer Basics Risk Factors ... earlier. So what are the warning signs of prostate cancer? Unfortunately, there usually aren’t any early warning ...

  11. Prostate cancer - treatment

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000403.htm Prostate cancer - treatment To use the sharing features on this page, ... drugs is recommended. References National Cancer Institute. Prostate cancer treatment (PDQ): Stages of prostate cancer. Updated July 31, ...

  12. Beta-carotene Antioxidant Use During Radiation Therapy and Prostate Cancer Outcome in the Physicians' Health Study

    International Nuclear Information System (INIS)

    Margalit, Danielle N.; Kasperzyk, Julie L.; Martin, Neil E.; Sesso, Howard D.; Gaziano, John Michael; Ma, Jing; Stampfer, Meir J.; Mucci, Lorelei A.

    2012-01-01

    Purpose: The safety of antioxidant supplementation during radiation therapy (RT) for cancer is controversial. Antioxidants could potentially counteract the pro-oxidant effects of RT and compromise therapeutic efficacy. We performed a prospective study nested within the Physicians’ Health Study (PHS) randomized trial to determine if supplemental antioxidant use during RT for prostate cancer is associated with an increased risk of prostate cancer death or metastases. Methods and Materials: PHS participants (383) received RT for prostate cancer while randomized to receive beta-carotene (50 mg on alternate days) or placebo. The primary endpoint was time from RT to lethal prostate cancer, defined as prostate cancer death or bone metastases. The Kaplan-Meier method was used to estimate survival probabilities and the log-rank test to compare groups. Cox proportional hazards regression was used to estimate the effect of beta-carotene compared with that of placebo during RT. Results: With a median follow-up of 10.5 years, there was no significant difference between risk of lethal prostate cancer with the use of beta-carotene during RT compared with that of placebo (hazard ratio = 0.72; 95% confidence interval [CI], 0.42–1.24; p = 0.24). After we adjusted for age at RT, prostate-specific antigen serum level, Gleason score, and clinical stage, the difference remained nonsignificant. The 10-year freedom from lethal prostate cancer was 92% (95% CI, 87–95%) in the beta-carotene group and 89% (95% CI, 84–93%) in the placebo group. Conclusion: The use of supplemental antioxidant beta-carotene during RT was not associated with an increased risk of prostate cancer death or metastases. This study suggests a lack of harm from supplemental beta-carotene during RT for prostate cancer.

  13. Zinc in human prostate gland. Normal, hyperplastic and cancerous

    International Nuclear Information System (INIS)

    Zaichick, V.Ye.; Sviridova, T.V.; Zaichick, S.V.

    1997-01-01

    Zinc concentration in a prostate gland is much higher than that in other human tissues. Data about zinc changes for different prostate diseases are limited and greatly contradictory. Zinc content was determined for biopsy and resected materials of transrectal puncture tissues from benign prostate hyperplasia (BPH) and prostate cancer. There were 109 patients (50 BPH and 59 cancer) available for the present study. Control group consisted of 37 intact glands of men died an unexpected death (accident, murder, acute cardiac insufficiency, etc.). All materials studied were divided into two parts. One of them was morphologically examined, while another one was subjected to zinc analysis by INAA. Zinc contents (M ± SE) of normal, benign hyperplastic and cancerous prostate glands were found to be 1018 ± 124, 1142 ± 77, and 146 ± 10 μg/g dry tissue, respectively. It was shown that zinc assessments in the materials of transrectal puncture biopsy of indurated prostate sites can be used as an additional test for differential diagnostics of BPH and cancer. Accuracy, sensitivity and specificity of the test are 98 ± 2%. (author)

  14. Nerve Growth Factor in Cancer Cell Death and Survival

    Energy Technology Data Exchange (ETDEWEB)

    Molloy, Niamh H.; Read, Danielle E.; Gorman, Adrienne M., E-mail: adrienne.gorman@nuigalway.ie [Apoptosis Research Centre, School of Natural Sciences, National University of Ireland, Galway (Ireland)

    2011-02-01

    One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75{sup NTR}, a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75{sup NTR}. For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75{sup NTR}. This latter signaling through p75{sup NTR} promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75{sup NTR} mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer.

  15. Paucity of PD-L1 expression in prostate cancer: innate and adaptive immune resistance.

    Science.gov (United States)

    Martin, A M; Nirschl, T R; Nirschl, C J; Francica, B J; Kochel, C M; van Bokhoven, A; Meeker, A K; Lucia, M S; Anders, R A; DeMarzo, A M; Drake, C G

    2015-12-01

    Primary prostate cancers are infiltrated with programmed death-1 (PD-1) expressing CD8+ T-cells. However, in early clinical trials, men with metastatic castrate-resistant prostate cancer did not respond to PD-1 blockade as a monotherapy. One explanation for this unresponsiveness could be that prostate tumors generally do not express programmed death ligand-1 (PD-L1), the primary ligand for PD-1. However, lack of PD-L1 expression in prostate cancer would be surprising, given that phosphatase and tensin homolog (PTEN) loss is relatively common in prostate cancer and several studies have shown that PTEN loss correlates with PD-L1 upregulation--constituting a mechanism of innate immune resistance. This study tested whether prostate cancer cells were capable of expressing PD-L1, and whether the rare PD-L1 expression that occurs in human specimens correlates with PTEN loss. Human prostate cancer cell lines were evaluated for PD-L1 expression and loss of PTEN by flow cytometry and western blotting, respectively. Immunohistochemical (IHC) staining for PTEN was correlated with PD-L1 IHC using a series of resected human prostate cancer samples. In vitro, many prostate cancer cell lines upregulated PD-L1 expression in response to inflammatory cytokines, consistent with adaptive immune resistance. In these cell lines, no association between PTEN loss and PD-L1 expression was apparent. In primary prostate tumors, PD-L1 expression was rare, and was not associated with PTEN loss. These studies show that some prostate cancer cell lines are capable of expressing PD-L1. However, in human prostate cancer, PTEN loss is not associated with PD-L1 expression, arguing against innate immune resistance as a mechanism that mitigates antitumor immune responses in this disease.

  16. Prostate Cancer Incidence and Mortality in Barbados, West Indies

    Directory of Open Access Journals (Sweden)

    Anselm J. M. Hennis

    2011-01-01

    Full Text Available We describe prostate cancer incidence and mortality in Barbados, West Indies. We ascertained all histologically confirmed cases of prostate cancer during the period July 2002 to December 2008 and reviewed each death registration citing prostate cancer over a 14-year period commencing January 1995. There were 1101 new cases for an incidence rate of 160.4 (95% Confidence Interval: 151.0–170.2 per 100,000 standardized to the US population. Comparable rates in African-American and White American men were 248.2 (95% CI: 246.0–250.5 and 158.0 (95% CI: 157.5–158.6 per 100,000, respectively. Prostate cancer mortality rates in Barbados ranged from 63.2 to 101.6 per 100,000, compared to 51.1 to 78.8 per 100,000 among African Americans. Prostate cancer risks are lower in Caribbean-origin populations than previously believed, while mortality rates appeared to be higher than reported in African-American men. Studies in Caribbean populations may assist understanding of disparities among African-origin populations with shared heredity.

  17. Perineural Invasion Predicts Increased Recurrence, Metastasis, and Death From Prostate Cancer Following Treatment With Dose-Escalated Radiation Therapy

    International Nuclear Information System (INIS)

    Feng, Felix Y.; Qian Yushen; Stenmark, Matthew H.; Halverson, Schuyler; Blas, Kevin; Vance, Sean; Sandler, Howard M.; Hamstra, Daniel A.

    2011-01-01

    Purpose: To assess the prognostic value of perineural invasion (PNI) for patients treated with dose-escalated external-beam radiation therapy for prostate cancer. Methods and Materials: Outcomes were analyzed for 651 men treated for prostate cancer with EBRT to a minimum dose ≥75 Gy. We assessed the impact of PNI as well as pretreatment and treatment-related factors on freedom from biochemical failure (FFBF), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival. Results: PNI was present in 34% of specimens at biopsy and was significantly associated with higher Gleason score (GS), T stage, and prostate-specific antigen level. On univariate and multivariate analysis, the presence of PNI was associated with worse FFBF (hazard ratio = 1.7, p <0.006), FFM (hazard ratio = 1.8, p <0.03), and CSS (HR = 1.4, p <0.05) compared with absence of PNI; there was no difference in overall survival. Seven-year rates of FFBF, FFM, and CCS were 64% vs. 80%, 84% vs. 92%, and 91% vs. 95% for those patients with and without PNI, respectively. On recursive partitioning analysis, PNI predicted for worse FFM and CSS in patients with GS 8–10, with FFM of 67% vs. 89% (p <0.02), and CSS of 69% vs. 91%, (p <0.04) at 7 years for those with and without PNI, respectively. Conclusions: The presence of PNI in the prostate biopsy predicts worse clinical outcome for patients treated with dose-escalated external-beam radiation therapy. Particularly in patients with GS 8–10 disease, the presence of PNI suggests an increased risk of metastasis and prostate cancer death.

  18. Perineural Invasion Predicts Increased Recurrence, Metastasis, and Death From Prostate Cancer Following Treatment With Dose-Escalated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Felix Y. [University of Michigan Medical Center, Ann Arbor, MI (United States); Ann Arbor Veteran Affairs Medical System, Ann Arbor, MI (United States); Qian Yushen; Stenmark, Matthew H.; Halverson, Schuyler; Blas, Kevin; Vance, Sean [University of Michigan Medical Center, Ann Arbor, MI (United States); Sandler, Howard M. [Cedars Sinai Medical System, Los Angeles, CA (United States); Hamstra, Daniel A., E-mail: dhamm@med.umich.edu [University of Michigan Medical Center, Ann Arbor, MI (United States)

    2011-11-15

    Purpose: To assess the prognostic value of perineural invasion (PNI) for patients treated with dose-escalated external-beam radiation therapy for prostate cancer. Methods and Materials: Outcomes were analyzed for 651 men treated for prostate cancer with EBRT to a minimum dose {>=}75 Gy. We assessed the impact of PNI as well as pretreatment and treatment-related factors on freedom from biochemical failure (FFBF), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival. Results: PNI was present in 34% of specimens at biopsy and was significantly associated with higher Gleason score (GS), T stage, and prostate-specific antigen level. On univariate and multivariate analysis, the presence of PNI was associated with worse FFBF (hazard ratio = 1.7, p <0.006), FFM (hazard ratio = 1.8, p <0.03), and CSS (HR = 1.4, p <0.05) compared with absence of PNI; there was no difference in overall survival. Seven-year rates of FFBF, FFM, and CCS were 64% vs. 80%, 84% vs. 92%, and 91% vs. 95% for those patients with and without PNI, respectively. On recursive partitioning analysis, PNI predicted for worse FFM and CSS in patients with GS 8-10, with FFM of 67% vs. 89% (p <0.02), and CSS of 69% vs. 91%, (p <0.04) at 7 years for those with and without PNI, respectively. Conclusions: The presence of PNI in the prostate biopsy predicts worse clinical outcome for patients treated with dose-escalated external-beam radiation therapy. Particularly in patients with GS 8-10 disease, the presence of PNI suggests an increased risk of metastasis and prostate cancer death.

  19. Prostate cancer: The main risk and protective factors-Epigenetic modifications.

    Science.gov (United States)

    Adjakly, Mawussi; Ngollo, Marjolaine; Dagdemir, Aslihan; Judes, Gaëlle; Pajon, Amaury; Karsli-Ceppioglu, Seher; Penault-Llorca, Frédérique; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

    2015-02-01

    With 13 million new cases worldwide every year, prostate cancer is as a very real public health concern. Prostate cancer is common in over-50s men and the sixth-leading cause of cancer-related death in men worldwide. Like all cancers, prostate cancer is multifactorial - there are non-modifiable risk factors like heredity, ethnicity and geographic location, but also modifiable risk factors such as diet. Diet-cancer linkages have risen to prominence in the last few years, with accruing epidemiological data pointing to between-population incidence differentials in numerous cancers. Indeed, there are correlations between fat-rich diet and risk of hormone-dependent cancers like prostate cancer and breast cancer. Diet is a risk factor for prostate cancer, but certain micronutrients in specific diets are considered protective factors against prostate cancer. Examples include tomato lycopene, green tea epigallocatechin gallate, and soy phytoestrogens. These micronutrients are thought to exert cancer-protective effects via anti-oxidant pathways and inhibition of cell proliferation. Here, we focus in on the effects of phytoestrogens, and chiefly genistein and daidzein, which are the best-researched to date. Soy phytoestrogens are nonsteroid molecules whose structural similarity lends them the ability to mimic the effects of 17ß-estradiol. On top of anti-oxidant effects, there is evidence that soy phytoestrogens can modulate the epigenetic modifications found in prostate cancer. We also studied the impact of phytoestrogens on epigenetic modifications in prostate cancer, with special focus on DNA methylation, miRNA-mediated regulation and histone modifications. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  20. New possibilities and view for treatment of castration resistant prostate cancer

    International Nuclear Information System (INIS)

    Barilla, R.; Andrasina, I.

    2012-01-01

    Prostate cancer is currently known as the most common cancer and the second leading cause of death from cancer in men in Western population. Advanced prostate cancer is initially sensitive to androgen-deprivation therapy (ADT) but later on progresses to castration resistant state. Understanding the mechanisms that transform prostate cancer (PCA) into a castration-resistant state enables investigators to explore suppression of extraresticular andronegs and other critical pathways to suggest appropriate and rational therapeutic design. Docetaxel based chemotherapy is established as the standard first line chemotherapy in patients with metastatic castration-resistant advanced prostate cancer with improved survival. However, prognosis remains poor and median survival is usually not longer than 2 years. Several Phase III studies have been completed recently, e.g. with new antiandrogens, new taxanes, immunotherapy and therapeutic antibodies. Multidisciplinary management and optimization of their role and and the most appropriate timing is the most important task in the treatment of advanced prostate cancer. (author)

  1. The role of cannabinoids in prostate cancer: Basic science perspective and potential clinical applications

    Directory of Open Access Journals (Sweden)

    Juan A Ramos

    2012-01-01

    Full Text Available Prostate cancer is a global public health problem, and it is the most common cancer in American men and the second cause for cancer-related death. Experimental evidence shows that prostate tissue possesses cannabinoid receptors and their stimulation results in anti-androgenic effects. To review currently relevant findings related to effects of cannabinoid receptors in prostate cancer. PubMed search utilizing the terms "cannabis," "cannabinoids," "prostate cancer," and "cancer pain management," giving preference to most recent publications was done. Articles identified were screened for their relevance to the field of prostate cancer and interest to both urologist and pain specialists. Prostate cancer cells possess increased expression of both cannabinoid 1 and 2 receptors, and stimulation of these results in decrease in cell viability, increased apoptosis, and decreased androgen receptor expression and prostate-specific antigen excretion. It would be of interest to conduct clinical studies utilizing cannabinoids for patients with metastatic prostate cancer, taking advantage not only of its beneficial effects on prostate cancer but also of their analgesic properties for bone metastatic cancer pain.

  2. Perceived causes of prostate cancer among prostate cancer survivors in the Netherlands

    NARCIS (Netherlands)

    Kok, D.E.G.; Cremers, R.G.H.M.; Aben, K.K.H.; Oort, van I.M.; Kampman, E.; Kiemeney, L.A.L.M.

    2013-01-01

    Introduction The aim of this study was to evaluate self-reported causes of prostate cancer among prostate cancer survivors in the Netherlands to obtain insight into the common beliefs and perceptions of risk factors for prostate cancer. Materials and methods A total of 956 prostate cancer survivors,

  3. Chelerythrine induced cell death through ROS-dependent ER stress in human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Wu S

    2018-05-01

    Full Text Available Songjiang Wu, Yanying Yang, Feiping Li, Lifu Huang, Zihua Han, Guanfu Wang, Hongyuan Yu, Haiping Li Department of Urology, Enze Hospital of Taizhou Enze Medical Center (Group, Taizhou, China Introduction: Prostate cancer is the most common noncutaneous cancer and the second leading cause of cancer-related mortality worldwide and the third in USA in 2017. Chelerythrine (CHE, a naturalbenzo[c]phenanthridine alkaloid, formerly identified as a protein kinase C inhibitor, has also shown anticancer effect through a number of mechanisms. Herein, effect and mechanism of the CHE-induced apoptosis via reactive oxygen species (ROS-mediated endoplasmic reticulum (ER stress in prostate cancer cells were studied for the first time. Methods: In our present study, we investigated whether CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a dose-dependent manner in PC-3 cells. In addition, we showed that CHE increases intracellular ROS and leads to ROS-dependent ER stress and cell apoptosis. Results: Pre-treatment with N-acetyl cysteine, an ROS scavenger, totally reversed the CHE-induced cancer cell apoptosis as well as ER stress activation, suggesting that the ROS generation was responsible for the anticancer effects of CHE. Conclusion: Taken together, our findings support one of the anticancer mechanisms by which CHE increased ROS accumulation in prostate cancer cells, thereby leading to ER stress and caused intrinsic apoptotic signaling. The study reveals that CHE could be a potential candidate for application in the treatment of prostate cancer. Keywords: chelerythrine, reactive oxygen species, endoplasmic reticulum stress, apoptosis, prostate cancer

  4. Non-Steroidal Anti-Inflammatory Drugs and Cancer Death in the Finnish Prostate Cancer Screening Trial.

    Directory of Open Access Journals (Sweden)

    Thea Veitonmäki

    Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs, especially aspirin, have been associated with lowered cancer incidence and mortality. We examined overall cancer mortality and mortality from specific cancer sites among the 80,144 men in the Finnish Prostate Cancer Screening Trial. Information on prescription drug use was acquired from the national drug reimbursement database. Over-the-counter use information was gathered by a questionnaire. Hazard ratios (HR and 95% confidence intervals (CI by prescription and over-the-counter NSAID use for overall and specific cancer deaths were calculated using Cox regression. During the median follow-up time of 15 years, 7,008 men died from cancer. Men with prescription NSAID use had elevated cancer mortality (HR 2.02 95% CI 1.91-2.15 compared to non-users. The mortality risk was increased for lung, colorectal and pancreas cancer mortality (HR 2.68, 95%CI 2.40-2.99, HR 1.91, 95% CI 1.57-2.32 and HR 1.93, 95% CI 1.58-2.37, respectively. The increased risk remained in competing risks regression (HR 1.11, 95% CI 1.05-1.18. When the usage during the last three years of follow-up was excluded, the effect was reversed (HR 0.69, 95% CI 0.65-0.73. Cancer mortality was not decreased for prescription or over-the-counter aspirin use. However, in the competing risk regression analysis combined prescription and over-the-counter aspirin use was associated with decreased overall cancer mortality (HR 0.76, 95% CI 0.70-0.82. Cancer mortality was increased for NSAID users. However, the risk disappeared when the last 3 years were excluded.

  5. Prostatic carcinoma. Diagnostic and stating: MR imaging. Cancer de la prostate Diagnostic et bilan: role de l'imagerie

    Energy Technology Data Exchange (ETDEWEB)

    Roy, C; Spittler, G; Jacqmin, D [Centre Hospitalier Universitaire, 67 - Strasbourg (FR); Morel, M [Clinique Saint-Francois, 67 Haguenau (FR)

    1991-01-01

    Prostatic carcinoma is the second most commun cause of cancer death over 60 years. It is suspected by digital examination and prostatic specific antigen dosage. Transrectal ultrasound shows the tumor as an hypoechoic lesion. Sensitivity is good but specificity is low. Transrectal biopsy of prostate guided by transrectal ultrasound made the diagnosis. At present, MR Imaging is the most accurate diagnostic modality for loco-regional staging of prostatic carcinoma.

  6. QuickStats: Age-Adjusted Death Rates* for Top Five Causes of Cancer Death,(†) by Race/Hispanic Ethnicity - United States, 2014.

    Science.gov (United States)

    2016-09-16

    In 2014, the top five causes of cancer deaths for the total population were lung, colorectal, female breast, pancreatic, and prostate cancer. The non-Hispanic black population had the highest age-adjusted death rates for each of these five cancers, followed by non-Hispanic white and Hispanic groups. The age-adjusted death rate for lung cancer, the leading cause of cancer death in all groups, was 42.1 per 100,000 standard population for the total population, 45.4 for non-Hispanic white, 45.7 for non-Hispanic black, and 18.3 for Hispanic populations.

  7. Night work and prostate cancer in men: a Swedish prospective cohort study.

    Science.gov (United States)

    Åkerstedt, Torbjrn; Narusyte, Jurgita; Svedberg, Pia; Kecklund, Göran; Alexanderson, Kristina

    2017-06-08

    Prostate cancer is the most common cancer and the second leading cause of cancer-related deaths among men, but the contributing factors are unclear. One such may be night work because of the day/night alternation of work and the resulting disturbance of the circadian system. The purpose of the present study was to investigate the prospective relation between number of years with night work and prostate cancer in men. Cohort study comparing night and day working twins with respect to incident prostate cancer in 12 322 men. Individuals in the Swedish Twin Registry. 12 322 male twins. Prostate cancer diagnoses obtained from the Swedish Cancer Registry with a follow-up time of 12 years, with a total number of cases=454. Multiple Cox proportional hazard regression analysis, adjusted for a number of covariates, showed no association between ever night work and prostate cancer, nor for duration of night work and prostate cancer. Analysis of twin pairs discordant for prostate cancer (n=332) showed no significant association between night work and prostate cancer. The results, together with previous studies, suggest that night work does not seem to constitute a risk factor for prostate cancer. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

    Science.gov (United States)

    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

  9. Causes of Mortality After Dose-Escalated Radiation Therapy and Androgen Deprivation for High-Risk Prostate Cancer

    International Nuclear Information System (INIS)

    Tendulkar, Rahul D.; Hunter, Grant K.; Reddy, Chandana A.; Stephans, Kevin L.; Ciezki, Jay P.; Abdel-Wahab, May; Stephenson, Andrew J.; Klein, Eric A.; Mahadevan, Arul; Kupelian, Patrick A.

    2013-01-01

    Purpose: Men with high-risk prostate cancer have other competing causes of mortality; however, current risk stratification schema do not account for comorbidities. We aim to identify the causes of death and factors predictive for mortality in this population. Methods and Materials: A total of 660 patients with high-risk prostate cancer were treated with definitive high-dose external beam radiation therapy (≥74 Gy) and androgen deprivation (AD) between 1996 and 2009 at a single institution. Cox proportional hazards regression analysis was conducted to determine factors predictive of survival. Results: The median radiation dose was 78 Gy, median duration of AD was 6 months, and median follow-up was 74 months. The 10-year overall survival (OS) was 60.6%. Prostate cancer was the leading single cause of death, with 10-year mortality of 14.1% (95% CI 10.7-17.6), compared with other cancers (8.4%, 95% CI 5.7-11.1), cardiovascular disease (7.3%, 95% CI 4.7-9.9), and all other causes (10.4%, 95% CI 7.2-13.6). On multivariate analysis, older age (HR 1.55, P=.002) and Charlson comorbidity index score (CS) ≥1 (HR 2.20, P<.0001) were significant factors predictive of OS, whereas Gleason score, T stage, prostate-specific antigen, duration of AD, radiation dose, smoking history, and body mass index were not. Men younger than 70 years of age with CS = 0 were more likely to die of prostate cancer than any other cause, whereas older men or those with CS ≥1 more commonly suffered non-prostate cancer death. The cumulative incidences of prostate cancer-specific mortality were similar regardless of age or comorbidities (P=.60). Conclusions: Men with high-risk prostate cancer are more likely to die of causes other than prostate cancer, except for the subgroup of men younger than 70 years of age without comorbidities. Only older age and presence of comorbidities significantly predicted for OS, whereas prostate cancer- and treatment-related factors did not

  10. The changing age distribution of prostate cancer in Canada.

    Science.gov (United States)

    Neutel, C Ineke; Gao, Ru-Nie; Blood, Paul A; Gaudette, Leslie A

    2007-01-01

    Prostate cancer incidence rates are still increasing steadily; mortality rates are levelling, possibly decreasing; and hospitalization rates for many diagnoses are decreasing. Our objective is to examine changes in age distributions of prostate cancer during these times of change. Prostate cancer cases were derived from the Canadian Cancer Registry, prostate cancer deaths from Vital Statistics, hospitalizations from the Hospital Morbidity File. Age-standardized rates were calculated based on the 1991 Canadian population. A prevalence correction for incidence rates was calculated. Age-specific incidence rates increased until 1995 for all ages, but a superimposed peak (1991-94) was greatest between ages 60-79. After 1995, increases in incidence continued for the under-70 age groups. Prevalence correction indicated the greatest underestimation of incidence rates for the oldest ages, but was less in Canada than in the United States. Mortality rates increased until 1994, then levelled and slowly decreased; age-specific mortality rates showed the greatest increase for the oldest ages but the earliest downturn for younger age groups. While hospitalizations dropped drastically after 1991, this drop was confined to elderly men (70+). Dramatic changes in age distributions of prostate cancer incidence, mortality and hospitalizations altered age profiles of men with prostate cancer. This illustrated the changing nature of prostate cancer as a public health issue and has important implications for health care provision, e.g., the increased numbers of younger new patients have different needs from the increasing numbers of elderly long-term patients who now spend less time in hospital.

  11. Osteoblast-Prostate Cancer Cell Interaction in Prostate Cancer Bone Metastases

    National Research Council Canada - National Science Library

    Navone, Nora

    2001-01-01

    .... This suggests that prostate cancer cells interact with cells from the osteoblastic lineage. To understand the molecular bases of prostatic bone metastases, we established two prostate cancer cell lines, MDA PCa 2a and MDA PCa 2b (1...

  12. Prostate Cancer Ambassadors

    Science.gov (United States)

    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

  13. Activation of the hedgehog pathway in advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    McCormick Frank

    2004-10-01

    Full Text Available Abstract Background The hedgehog pathway plays a critical role in the development of prostate. However, the role of the hedgehog pathway in prostate cancer is not clear. Prostate cancer is the second most prevalent cause of cancer death in American men. Therefore, identification of novel therapeutic targets for prostate cancer has significant clinical implications. Results Here we report that activation of the hedgehog pathway occurs frequently in advanced human prostate cancer. We find that high levels of hedgehog target genes, PTCH1 and hedgehog-interacting protein (HIP, are detected in over 70% of prostate tumors with Gleason scores 8–10, but in only 22% of tumors with Gleason scores 3–6. Furthermore, four available metastatic tumors all have high expression of PTCH1 and HIP. To identify the mechanism of the hedgehog signaling activation, we examine expression of Su(Fu protein, a negative regulator of the hedgehog pathway. We find that Su(Fu protein is undetectable in 11 of 27 PTCH1 positive tumors, two of them contain somatic loss-of-function mutations of Su(Fu. Furthermore, expression of sonic hedgehog protein is detected in majority of PTCH1 positive tumors (24 out of 27. High levels of hedgehog target genes are also detected in four prostate cancer cell lines (TSU, DU145, LN-Cap and PC3. We demonstrate that inhibition of hedgehog signaling by smoothened antagonist, cyclopamine, suppresses hedgehog signaling, down-regulates cell invasiveness and induces apoptosis. In addition, cancer cells expressing Gli1 under the CMV promoter are resistant to cyclopamine-mediated apoptosis. All these data suggest a significant role of the hedgehog pathway for cellular functions of prostate cancer cells. Conclusion Our data indicate that activation of the hedgehog pathway, through loss of Su(Fu or overexpression of sonic hedgehog, may involve tumor progression and metastases of prostate cancer. Thus, targeted inhibition of hedgehog signaling may have

  14. Radiation therapy of newly diagnosed, advanced prostatic cancer and hormonally relapsed prostatic cancer

    International Nuclear Information System (INIS)

    Suzuki, Minoru; Fujiwara, Kazuhisa; Hayakawa, Katsumi; Hida, Shuichi

    1994-01-01

    Ten patients with newly diagnosed, advanced prostatic cancer were treated with radiotherapy and hormone therapy to improve tumor control and survival. Eight patients with hormonally relapsed prostatic cancer were treated with radiotherapy to improve their quality of life. Local control of the tumor was achieved in 9 of 10 patients with newly diagnosed, advanced prostatic cancer. Five of eight patients with hormonally relapsed prostatic cancer obtained improved quality of life. Combined radiotherapy and hormone therapy were effective in the treatment of newly diagnosed, advanced prostatic cancer, and radiotherapy was useful for improving the quality of life of patients with hormonally relapsed prostatic cancer. (author)

  15. Role of miRNA Let-7 and Its Major Targets in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Siegfried Wagner

    2014-01-01

    Full Text Available Prostate cancer is worldwide the sixth leading cause of cancer related death in men thus early detection and successful treatment are still of major interest. The commonly performed screening of the prostate-specific antigen (PSA is controversially discussed, as in many patients the prostate-specific antigen levels are chronically elevated in the absence of cancer. Due to the unsatisfying efficiency of available prostate cancer screening markers and the current treatment outcome of the aggressive hormone refractory prostate cancer, the evaluation of novel molecular markers and targets is considered an issue of high importance. MicroRNAs are relatively stable in body fluids orchestrating simultaneously the expression of many genes. These molecules are currently discussed to bear a greater diagnostic potential than protein-coding genes, being additionally promising therapeutic drugs and/or targets. Herein we review the potential impact of the microRNA let-7 family on prostate cancer and show how deregulation of several of its target genes could influence the cellular equilibrium in the prostate gland, promoting cancer development as they do in a variety of other human malignant neoplasias.

  16. Prostate Cancer Screening : The effect on prostate cancer mortality and incidence

    NARCIS (Netherlands)

    P.J. van Leeuwen (Pim)

    2012-01-01

    textabstractAt first glance, deciding whether to get the PSA screening test for prostate cancer seems to be pretty straightforward and attractive. It’s a simple blood test that can pick up the prostate cancer long before your symptoms appear. After all, your prostate cancer is earlier treated

  17. Prostate Cancer

    Science.gov (United States)

    ... 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 ...

  18. Molecular biology of prostate cancer progression

    International Nuclear Information System (INIS)

    Thompson, Timothy C.; Sehgal, I.; Timme, T.L.; Rn, C.; Yang, G.; Park, S.H.

    1996-01-01

    Prostate cancer is now the most common form of cancer and the second leading cause of cancer deaths in American men (Boring C.C. et al, CA 44:7-26, 1994). As with other forms of cancer, prostate cancer is a multistep disease process that involves the acquisition of multiple genetic alternations (Armitage P and Doll K, Br J Cancer 8:1-12, 1954). For prostate cancer, alternations in specific dominantly acting oncogenes including ras and myc and tumor suppressor genes including p53 and Rb have been reported. However, a simple phenotype-genotype correlation for prostate cancer progression may not be readily accessible because prostate cancer demonstrates remarkable genetic heterogeneity. Recent clinical data indicate that this heterogeneity exists both among the multiple cancer foci as well as within individual cancer foci. Furthermore, based on chromosomal analysis, it has been suggested that metastases do not necessarily seed from the largest index cancer focus at the primary site. Such observations imply that abrupt changes in gene expression may trigger metastatic behavior in relatively small cohorts of malignant cells present at the local site. This pattern of progression may result from compromised function of specific 'control' genes which could affect the activity of multiple downstream genes involved in specific pathways of malignant progression. Such a mechanistic framework involving networks of gene expression could explain the acquisition of the complex metastatic phenotype. Using the mouse prostate reconstitution (MPR) model system (Thompson et al, Cell 56:917-930, 1989) we demonstrated that progression of experimental prostate cancer to metastasis was invariably associated with functional inactivation of p53 (Thompson el al, Oncogene 10:869-879, 1995). Southern blotting analyses revealed that metastases do not necessarily originate from the most abundant clone in the primary carcinoma. Furthermore, the role of p53 as a potential metastasis suppressor

  19. Prostate cancer epigenome.

    Science.gov (United States)

    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.

  20. Prostate Cancer Screening in Jamaica: Results of the Largest National Screening Clinic Prostate Cancer Screening in Jamaica: Results of the Largest National Screening Clinic

    International Nuclear Information System (INIS)

    Morrison, B. F.; Aiken, W.; Mayhew, R.; Gordon, Y.; Reid, M.

    2016-01-01

    Prostate cancer is highly prevalent in Jamaica and is the leading cause of cancer-related deaths. Our aim was to evaluate the patterns of screening in the largest organized screening clinic in Jamaica at the Jamaica Cancer Society. A retrospective analysis of all men presenting for screening at the Jamaica Cancer Society from 1995 to 2005 was done. All patients had digital rectal examinations (DRE) and prostate specific antigen (PSA) tests done. Results of prostate biopsies were noted. 1117 men of mean age 59.9 ± 8.2 years presented for screening. The median documented PSA was 1.6 ng/mL (maximum of 5170 ng/mL). Most patients presented for only 1 screen. There was a gradual reduction in the mean age of presentation for screening over the period. Prostate biopsies were requested on 11% of screening visits; however, only 59% of these were done. 5.6% of all persons screened were found to have cancer. Of the cancers diagnosed, Gleason 6 adenocarcinoma was the commonest grade and median PSA was 8.9 ng/mL (range 1.5-1059 ng/mL). Older men tend to screen for prostate cancer in Jamaica. However, compliance with regular maintenance visits and requests for confirmatory biopsies are poor. Screening needs intervention in the Jamaican population.

  1. Review article: Prostate cancer screening using prostate specific ...

    African Journals Online (AJOL)

    Background: Prostate cancer is the commonest cancer among men in Nigeria and early detection is key to cure and survival but its screening through prostate specific antigen (PSA) has remain controversial in literature. Screening with prostate specific antigen (PSA) has led to more men diagnosed with prostate cancer than ...

  2. New Insights into the Androgen-Targeted Therapies and Epigenetic Therapies in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Abhijit M. Godbole

    2011-01-01

    Full Text Available Prostate cancer is the most common cancer in men in the United States, and it is the second leading cause of cancer-related death in American men. The androgen receptor (AR, a receptor of nuclear family and a transcription factor, is the most important target in this disease. While most efforts in the clinic are currently directed at lowering levels of androgens that activate AR, resistance to androgen deprivation eventually develops. Most prostate cancer deaths are attributable to this castration-resistant form of prostate cancer (CRPC. Recent work has shed light on the importance of epigenetic events including facilitation of AR signaling by histone-modifying enzymes, posttranslational modifications of AR such as sumoylation. Herein, we provide an overview of the structure of human AR and its key structural domains that can be used as targets to develop novel antiandrogens. We also summarize recent findings about the antiandrogens and the epigenetic factors that modulate the action of AR.

  3. Alpha-tocopheryl succinate inhibits autophagic survival of prostate cancer cells induced by vitamin K3 and ascorbate to trigger cell death.

    Science.gov (United States)

    Tomasetti, Marco; Nocchi, Linda; Neuzil, Jiri; Goodwin, Jacob; Nguyen, Maria; Dong, Lanfeng; Manzella, Nicola; Staffolani, Sara; Milanese, Claudio; Garrone, Beatrice; Alleva, Renata; Borghi, Battista; Santarelli, Lory; Guerrieri, Roberto

    2012-01-01

    The redox-silent vitamin E analog α-tocopheryl succinate (α-TOS) was found to synergistically cooperate with vitamin K3 (VK3) plus ascorbic acid (AA) in the induction of cancer cell-selective apoptosis via a caspase-independent pathway. Here we investigated the molecular mechanism(s) underlying cell death induced in prostate cancer cells by α-TOS, VK3 and AA, and the potential use of targeted drug combination in the treatment of prostate cancer. The generation of ROS, cellular response to oxidative stress, and autophagy were investigated in PC3 prostate cancer cells by using drugs at sub-toxic doses. We evaluated whether PARP1-mediated apoptosis-inducing factor (AIF) release plays a role in apoptosis induced by the combination of the agents. Next, the effect of the combination of α-TOS, VK3 and AA on tumor growth was examined in nude mice. VK3 plus AA induced early ROS formation associated with induction of autophagy in response to oxidative stress, which was reduced by α-TOS, preventing the formation of autophagosomes. α-TOS induced mitochondrial destabilization leading to the release of AIF. Translocation of AIF from mitochondria to the nucleus, a result of the combinatorial treatment, was mediated by PARP1 activation. The inhibition of AIF as well as of PARP1 efficiently attenuated apoptosis triggered by the drug combination. Using a mouse model of prostate cancer, the combination of α-TOS, VK3 and AA was more efficient in tumor suppression than when the drugs were given separately, without deleterious side effects. α-TOS, a mitochondria-targeting apoptotic agent, switches at sub-apoptotic doses from autophagy-dependent survival of cancer cells to their demise by promoting the induction of apoptosis. Given the grim prognosis for cancer patients, this finding is of potential clinical relevance.

  4. Alpha-tocopheryl succinate inhibits autophagic survival of prostate cancer cells induced by vitamin K3 and ascorbate to trigger cell death.

    Directory of Open Access Journals (Sweden)

    Marco Tomasetti

    Full Text Available BACKGROUND: The redox-silent vitamin E analog α-tocopheryl succinate (α-TOS was found to synergistically cooperate with vitamin K3 (VK3 plus ascorbic acid (AA in the induction of cancer cell-selective apoptosis via a caspase-independent pathway. Here we investigated the molecular mechanism(s underlying cell death induced in prostate cancer cells by α-TOS, VK3 and AA, and the potential use of targeted drug combination in the treatment of prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS: The generation of ROS, cellular response to oxidative stress, and autophagy were investigated in PC3 prostate cancer cells by using drugs at sub-toxic doses. We evaluated whether PARP1-mediated apoptosis-inducing factor (AIF release plays a role in apoptosis induced by the combination of the agents. Next, the effect of the combination of α-TOS, VK3 and AA on tumor growth was examined in nude mice. VK3 plus AA induced early ROS formation associated with induction of autophagy in response to oxidative stress, which was reduced by α-TOS, preventing the formation of autophagosomes. α-TOS induced mitochondrial destabilization leading to the release of AIF. Translocation of AIF from mitochondria to the nucleus, a result of the combinatorial treatment, was mediated by PARP1 activation. The inhibition of AIF as well as of PARP1 efficiently attenuated apoptosis triggered by the drug combination. Using a mouse model of prostate cancer, the combination of α-TOS, VK3 and AA was more efficient in tumor suppression than when the drugs were given separately, without deleterious side effects. CONCLUSIONS/SIGNIFICANCE: α-TOS, a mitochondria-targeting apoptotic agent, switches at sub-apoptotic doses from autophagy-dependent survival of cancer cells to their demise by promoting the induction of apoptosis. Given the grim prognosis for cancer patients, this finding is of potential clinical relevance.

  5. The role of lipid-associated sialic acid (LSA) and prostate specific antigen (PSA) in the follow-up of prostatic cancer

    NARCIS (Netherlands)

    Meyer, U.; Dierig, C.; Katopodis, N.; Bruijn, de C.H.M.M.

    1993-01-01

    According to the most recent US cancer statistics, prostatic cancer almost equals lung cancer as the most frequent cause of death from cancer in men. The search for diagnostic methods as well as control examinations have therefore gained great importance. The present study reveals that--in addition

  6. Psychosocial and Quality of Life Issues in Prostate and Ovarian Cancer

    OpenAIRE

    Madalinska, J.B.

    2007-01-01

    textabstractProstate and ovarian cancers are among the leading causes of death in Western countries. Applied preventive health strategies, including screening and early medical treatments either with prophylactic or curative intention, may substantially affect patients’ quality of life (QOL). This thesis focuses on the psychosocial and QOL issues involved in the evaluation of early-detected and treated prostate cancer among men in the general population, and in the evaluation of preventive he...

  7. To Die or to Survive, a Fatal Question for the Destiny of Prostate Cancer Cells after Androgen Deprivation Therapy

    International Nuclear Information System (INIS)

    Zhang, Kai-Xin; Firus, Jessica; Prieur, Brenda; Jia, William; Rennie, Paul S.

    2011-01-01

    Prostate cancer is the most frequently diagnosed non-skin cancer in adult males in North America and is the second leading cause of cancer-related mortality. For locally advanced or metastatic disease, androgen deprivation, through medical or surgical castration, is the primary treatment to induce prostate cancer cell death and extend patient survival. However, the vast majority of cancers progress to a castration-resistant/androgen-independent state where the cell death processes are no longer active. This review describes the main cell death processes, apoptosis, autophagy, necrosis and necroptosis, which may be activated in prostate cancers after androgen deprivation therapy as well as the molecular mechanisms through which the cancers progress to become castration resistant. In particular, the central role of persistent androgen receptor (AR)-mediated signaling and AR crosstalk with other critical cell signaling pathways, including (i) the PI3K/Akt pathway, (ii) receptor tyrosine kinases, (iii) the p38 MAPK pathway, and (iv) the Wnt/β-catenin pathway, as well as reactivation of AR by de novo synthesized androgen are discussed in this context. Understanding the molecular changes that subvert normal cell death mechanisms and thereby compromise the survival of prostate cancer patients continues to be a major challenge

  8. To Die or to Survive, a Fatal Question for the Destiny of Prostate Cancer Cells after Androgen Deprivation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Kai-Xin; Firus, Jessica; Prieur, Brenda [The Vancouver Prostate Centre, 2660 Oak St., Vancouver, BC V6H 3Z6 (Canada); Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6 (Canada); Jia, William [Department of Surgery and Brain Research Centre, University of British Columbia, Vancouver, BC V6H 3Z6 (Canada); Rennie, Paul S., E-mail: prennie@interchange.ubc.ca [The Vancouver Prostate Centre, 2660 Oak St., Vancouver, BC V6H 3Z6 (Canada); Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6 (Canada)

    2011-03-24

    Prostate cancer is the most frequently diagnosed non-skin cancer in adult males in North America and is the second leading cause of cancer-related mortality. For locally advanced or metastatic disease, androgen deprivation, through medical or surgical castration, is the primary treatment to induce prostate cancer cell death and extend patient survival. However, the vast majority of cancers progress to a castration-resistant/androgen-independent state where the cell death processes are no longer active. This review describes the main cell death processes, apoptosis, autophagy, necrosis and necroptosis, which may be activated in prostate cancers after androgen deprivation therapy as well as the molecular mechanisms through which the cancers progress to become castration resistant. In particular, the central role of persistent androgen receptor (AR)-mediated signaling and AR crosstalk with other critical cell signaling pathways, including (i) the PI3K/Akt pathway, (ii) receptor tyrosine kinases, (iii) the p38 MAPK pathway, and (iv) the Wnt/β-catenin pathway, as well as reactivation of AR by de novo synthesized androgen are discussed in this context. Understanding the molecular changes that subvert normal cell death mechanisms and thereby compromise the survival of prostate cancer patients continues to be a major challenge.

  9. To Die or to Survive, a Fatal Question for the Destiny of Prostate Cancer Cells after Androgen Deprivation Therapy

    Directory of Open Access Journals (Sweden)

    Paul S. Rennie

    2011-03-01

    Full Text Available Prostate cancer is the most frequently diagnosed non-skin cancer in adult males in North America and is the second leading cause of cancer-related mortality. For locally advanced or metastatic disease, androgen deprivation, through medical or surgical castration, is the primary treatment to induce prostate cancer cell death and extend patient survival. However, the vast majority of cancers progress to a castration-resistant/androgen-independent state where the cell death processes are no longer active. This review describes the main cell death processes, apoptosis, autophagy, necrosis and necroptosis, which may be activated in prostate cancers after androgen deprivation therapy as well as the molecular mechanisms through which the cancers progress to become castration resistant. In particular, the central role of persistent androgen receptor (AR-mediated signaling and AR crosstalk with other critical cell signaling pathways, including (i the PI3K/Akt pathway, (ii receptor tyrosine kinases, (iii the p38 MAPK pathway, and (iv the Wnt/β-catenin pathway, as well as reactivation of AR by de novo synthesized androgen are discussed in this context. Understanding the molecular changes that subvert normal cell death mechanisms and thereby compromise the survival of prostate cancer patients continues to be a major challenge.

  10. Impact of short course hormonal therapy on overall and cancer specific survival after permanent prostate brachytherapy

    International Nuclear Information System (INIS)

    Beyer, David C.; McKeough, Timothy; Thomas, Theresa

    2005-01-01

    Purpose: To review the impact of prior hormonal therapy on 10-year overall and prostate cancer specific survival after primary brachytherapy. Methods and Materials: A retrospective review was performed on the Arizona Oncology Services tumor registry for 2,378 consecutive permanent prostate brachytherapy cases from 1988 through 2001. Hormonal therapy was administered before the implant in 464 patients for downsizing of the prostate or at the discretion of the referring physician. All deceased patients with known clinical recurrence were considered to have died of prostate cancer, irrespective of the immediate cause of death. Risk groups were defined, with 1,135 favorable (prostate-specific antigen [PSA] 70 years (p = 0.0013), Gleason score ≥ 7 (p = 0.0005), and prior hormone use (p = 0.0065) on overall survival. Conclusions: At 10 years, in prostate cancer patients receiving brachytherapy, overall survival is worse in men receiving neoadjuvant hormonal therapy, compared with hormone naive patients. This does not appear to be due to other known risk factors for survival (i.e., stage, grade, PSA, age) on multivariate analysis. The leading causes of death were cardiovascular, prostate cancer, and other cancers with no obvious discrepancy between the two groups. This finding is unexpected and requires confirmation from other centers

  11. Positive regulation of prostate cancer cell growth by lipid droplet forming and processing enzymes DGAT1 and ABHD5.

    Science.gov (United States)

    Mitra, Ranjana; Le, Thuc T; Gorjala, Priyatham; Goodman, Oscar B

    2017-09-06

    Neoplastic cells proliferate rapidly and obtain requisite building blocks by reprogramming metabolic pathways that favor growth. Previously, we observed that prostate cancer cells uptake and store lipids in the form of lipid droplets, providing building blocks for membrane synthesis, to facilitate proliferation and growth. Mechanisms of lipid uptake, lipid droplet dynamics and their contribution to cancer growth have yet to be defined. This work is focused on elucidating the prostate cancer-specific modifications in lipid storage pathways so that these modified gene products can be identified and therapeutically targeted. To identify genes that promote lipid droplet formation and storage, the expression profiles of candidate genes were assessed and compared between peripheral blood mononuclear cells and prostate cancer cells. Subsequently, differentially expressed genes were inhibited and growth assays performed to elucidate their role in the growth of the cancer cells. Cell cycle, apoptosis and autophagy assays were performed to ascertain the mechanism of growth inhibition. Our results indicate that DGAT1, ABHD5, ACAT1 and ATGL are overexpressed in prostate cancer cells compared to PBMCs and of these overexpressed genes, DGAT1 and ABHD5 aid in the growth of the prostate cancer cells. Blocking the expression of both DGAT1 and ABHD5 results in inhibition of growth, cell cycle block and cell death. DGAT1 siRNA treatment inhibits lipid droplet formation and leads to autophagy where as ABHD5 siRNA treatment promotes accumulation of lipid droplets and leads to apoptosis. Both the siRNA treatments reduce AMPK phosphorylation, a key regulator of lipid metabolism. While DGAT1 siRNA reduces phosphorylation of ACC, the rate limiting enzyme in de novo fat synthesis and triggers phosphorylation of raptor and ULK-1 inducing autophagy and cell death, ABHD5 siRNA decreases P70S6 phosphorylation, leading to PARP cleavage, apoptosis and cell death. Interestingly, DGAT-1 is involved

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

    Science.gov (United States)

    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 (pprostate 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

  13. A Biopsy-based 17-gene Genomic Prostate Score as a Predictor of Metastases and Prostate Cancer Death in Surgically Treated Men with Clinically Localized Disease.

    Science.gov (United States)

    Van Den Eeden, Stephen K; Lu, Ruixiao; Zhang, Nan; Quesenberry, Charles P; Shan, Jun; Han, Jeong S; Tsiatis, Athanasios C; Leimpeter, Amethyst D; Lawrence, H Jeffrey; Febbo, Phillip G; Presti, Joseph C

    2018-01-01

    A 17-gene biopsy-based reverse transcription polymerase chain reaction assay, which provides a Genomic Prostate Score (GPS-scale 0-100), has been validated as an independent predictor of adverse pathology and biochemical recurrence after radical prostatectomy (RP) in men with low- and intermediate-risk prostate cancer (PCa). To evaluate GPS as a predictor of PCa metastasis and PCa-specific death (PCD) in a large cohort of men with localized PCa and long-term follow-up. A retrospective study using a stratified cohort sampling design was performed in a cohort of men treated with RP within Kaiser Permanente Northern California. RNA from archival diagnostic biopsies was assayed to generate GPS results. We assessed the association between GPS and time to metastasis and PCD in prespecified uni- and multivariable statistical analyses, based on Cox proportional hazard models accounting for sampling weights. The final study population consisted of 279 men with low-, intermediate-, and high-risk PCa between 1995 and 2010 (median follow-up 9.8 yr), and included 64 PCD and 79 metastases. Valid GPS results were obtained for 259 (93%). In univariable analysis, GPS was strongly associated with time to PCD, hazard ratio (HR)/20 GPS units=3.23 (95% confidence interval [CI] 1.84-5.65; pstrong independent predictor of long-term outcomes in clinically localized PCa in men treated with RP and may improve risk stratification for men with newly diagnosed disease. Many prostate cancers are slow growing and unlikely to spread or threaten a man's life, while others are more aggressive and require treatment. Increasingly, doctors are using new molecular tests, such as the17-gene Genomic Prostate Score (GPS), which can be performed at the time of initial diagnosis to help determine how aggressive a given patient's cancer may be. In this study, performed in a large community-based healthcare network, GPS was shown to be a strong predictor as to whether a man's prostate cancer will spread and

  14. Diagnosis of prostate cancer via nanotechnological approach

    Directory of Open Access Journals (Sweden)

    Kang BJ

    2015-10-01

    Full Text Available Benedict J Kang,1,2,* Minhong Jeun,1,2,* Gun Hyuk Jang,1,2 Sang Hoon Song,3 In Gab Jeong,3 Choung-Soo Kim,3 Peter C Searson,4 Kwan Hyi Lee1,2 1KIST Biomedical Research Institute, 2Department of Biomedical Engineering, Korea University of Science and Technology (UST, 3Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 4Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA *These authors contributed equally to this work Abstract: Prostate cancer is one of the leading causes of cancer-related deaths among the Caucasian adult males in Europe and the USA. Currently available diagnostic strategies for patients with prostate cancer are invasive and unpleasant and have poor accuracy. Many patients have been overly or underly treated resulting in a controversy regarding the reliability of current conventional diagnostic approaches. This review discusses the state-of-the-art research in the development of novel noninvasive prostate cancer diagnostics using nanotechnology coupled with suggested diagnostic strategies for their clinical implication.Keywords: bioassay, nanomaterial, nanodevice, PSA, non-PSA biomarker, bodily fluid

  15. A Cost-Utility Analysis of Prostate Cancer Screening in Australia.

    Science.gov (United States)

    Keller, Andrew; Gericke, Christian; Whitty, Jennifer A; Yaxley, John; Kua, Boon; Coughlin, Geoff; Gianduzzo, Troy

    2017-02-01

    The Göteborg randomised population-based prostate cancer screening trial demonstrated that prostate-specific antigen (PSA)-based screening reduces prostate cancer deaths compared with an age-matched control group. Utilising the prostate cancer detection rates from this study, we investigated the clinical and cost effectiveness of a similar PSA-based screening strategy for an Australian population of men aged 50-69 years. A decision model that incorporated Markov processes was developed from a health system perspective. The base-case scenario compared a population-based screening programme with current opportunistic screening practices. Costs, utility values, treatment patterns and background mortality rates were derived from Australian data. All costs were adjusted to reflect July 2015 Australian dollars (A$). An alternative scenario compared systematic with opportunistic screening but with optimisation of active surveillance (AS) uptake in both groups. A discount rate of 5 % for costs and benefits was utilised. Univariate and probabilistic sensitivity analyses were performed to assess the effect of variable uncertainty on model outcomes. Our model very closely replicated the number of deaths from both prostate cancer and background mortality in the Göteborg study. The incremental cost per quality-adjusted life-year (QALY) for PSA screening was A$147,528. However, for years of life gained (LYGs), PSA-based screening (A$45,890/LYG) appeared more favourable. Our alternative scenario with optimised AS improved cost utility to A$45,881/QALY, with screening becoming cost effective at a 92 % AS uptake rate. Both modelled scenarios were most sensitive to the utility of patients before and after intervention, and the discount rate used. PSA-based screening is not cost effective compared with Australia's assumed willingness-to-pay threshold of A$50,000/QALY. It appears more cost effective if LYGs are used as the relevant outcome, and is more cost effective than the

  16. Prostate Cancer Foundation News

    Science.gov (United States)

    ... Finding a Doctor Treatment Options Side Effects Managing Prostate Cancer Treatment Related Side Effects Clinical Trials Patient Resources Guides Videos Prostate Cancer FAQs Information by Stage Newly Diagnosed with Prostate ...

  17. [Epigenetics of prostate cancer].

    Science.gov (United States)

    Yi, Xiao-Ming; Zhou, Wen-Quan

    2010-07-01

    Prostate cancer is one of the most common malignant tumors in males, and its etiology and pathogenesis remain unclear. Epigenesis is involved in prostate cancer at all stages of the process, and closely related with its growth and metastasis. DNA methylation and histone modification are the most important manifestations of epigenetics in prostate cancer. The mechanisms of carcinogenesis of DNA methylation include whole-genome hypomethylation, aberrant local hypermethylation of promoters and genomic instability. DNA methylation is closely related to the process of prostate cancer, as in DNA damage repair, hormone response, tumor cell invasion/metastasis, cell cycle regulation, and so on. Histone modification causes corresponding changes in chromosome structure and the level of gene transcription, and it may affect the cycle, differentiation and apoptosis of cells, resulting in prostate cancer. Some therapies have been developed targeting the epigenetic changes in prostate cancer, including DNA methyltransferases and histone deacetylase inhibitors, and have achieved certain desirable results.

  18. Imaging and prostate cancer

    International Nuclear Information System (INIS)

    Schwartz, Lawrence H.

    1996-01-01

    The use of imaging in evaluating patients with prostate cancer is highly dependent upon the purpose of the evaluation. Ultrasound, Computed Tomography, Magnetic Resonance Imaging, TC-99m Bone Scanning, and Positron Emission Tomography may all be utilized for imaging in prostate cancer. The utility of each of these modalities depends upon the intended purpose: for instance, screening, staging, or evaluating for progression of disease in patients with prostate cancer. Transrectal ultrasound is performed by placing a 5MHz to 7.5 MHz transducer in the rectum and imaging the prostate in the coronal and sagittal planes. Prostate cancer generally appears as an area of diminished echogenocity in the peripheral zone of the prostate gland. However, up to 24% of prostate cancers are isoechoic and cannot be well distinguished from the remainder of the peripheral zone. In addition, the incidence of malignancy in a lesion judged to be suspicious on ultrasound is between 20% and 25%. Therefore, while ultrasound is the least expensive of the three cross sectional imaging modalities, its relatively low specificity precludes it from being used as a screening examination. Investigators have also looked at the ability of ultrasound to evaluate the presence and extent of extracapsular spread of prostate cancer. The RDOG (Radiology Diagnostic Oncology Group) multi-institutional cooperative trial reported a disappointing overall accuracy of ultrasound of 58% for staging prostate cancer. The accuracy was somewhat higher 63%, for patients with advanced disease. The other cross-sectional imaging modalities available for imaging the prostate include Computed Tomography and Magnetic Resonance Imaging. Computed Tomography is useful as an 'anatomic' imaging technique to detect lymph node enlargement. It is not sensitive in detecting microscopic nodal involvement with tumor, or tumor in non-enlarged pelvic lymph nodes. The primary prostate neoplasm is generally the same attenuation as the normal

  19. The Danish Prostate Cancer Database

    DEFF Research Database (Denmark)

    Nguyen-Nielsen, Mary; Høyer, Søren; Friis, Søren

    2016-01-01

    variables include Gleason scores, cancer staging, prostate-specific antigen values, and therapeutic measures (active surveillance, surgery, radiotherapy, endocrine therapy, and chemotherapy). DESCRIPTIVE DATA: In total, 22,332 patients with prostate cancer were registered in DAPROCAdata as of April 2015......AIM OF DATABASE: The Danish Prostate Cancer Database (DAPROCAdata) is a nationwide clinical cancer database that has prospectively collected data on patients with incident prostate cancer in Denmark since February 2010. The overall aim of the DAPROCAdata is to improve the quality of prostate cancer...... care in Denmark by systematically collecting key clinical variables for the purposes of health care monitoring, quality improvement, and research. STUDY POPULATION: All Danish patients with histologically verified prostate cancer are included in the DAPROCAdata. MAIN VARIABLES: The DAPROCAdata...

  20. Prostate Cancer Biorepository Network

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-14-2-0185 TITLE: Prostate Cancer Biorepository Network PRINCIPAL INVESTIGATOR: Jonathan Melamed, MD CONTRACTING ORGANIZATION...AND SUBTITLE 5a. CONTRACT NUMBER Prostate Cancer Biorepository Network 5b. GRANT NUMBER W81XWH-14-2-0185 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...infrastructure and operations of the Prostate Cancer Biorepository Network (PCBN). The aim of the PCBN is to provide prostate researchers with high-quality

  1. The link between benign prostatic hyperplasia and prostate cancer

    DEFF Research Database (Denmark)

    Ørsted, David Dynnes; Bojesen, Stig E

    2013-01-01

    Benign prostatic hyperplasia (BPH) and prostate cancer are among the most common diseases of the prostate gland and represent significant burdens for patients and health-care systems in many countries. The two diseases share traits such as hormone-dependent growth and response to antiandrogen...... therapy. Furthermore, risk factors such as prostate inflammation and metabolic disruption have key roles in the development of both diseases. Despite these commonalities, BPH and prostate cancer exhibit important differences in terms of histology and localization. Although large-scale epidemiological...... studies have shown that men with BPH have an increased risk of prostate cancer and prostate-cancer-related mortality, it remains unclear whether this association reflects a causal link, shared risk factors or pathophysiological mechanisms, or detection bias upon statistical analysis. Establishing BPH...

  2. Interstitially implanted I125 for prostate cancer using transrectal ultrasound

    International Nuclear Information System (INIS)

    Greenburg, S.; Petersen, J.; Hansen-Peters, I.; Baylinson, W.

    1990-01-01

    Prostate cancer is the third leading cause of death from cancer among men in the United States. Traditional treatments for prostate cancer are prostatectomy, external beam irradiation, and interstitial implantation of Iodine125 (I125) via laparotomy. These treatments are associated with significant morbidity and limitations. Based on experience with I125 interstitial implantation by transrectal ultrasound guidance for early-stage prostate cancer, it seems that this newer method of treatment has greater accuracy of placement and distribution of the isotope and has had few reported complications. The need for a surgical incision has been eliminated. Hospitalization time also has been decreased, creating the need for ambulatory and inpatient nurses to understand the importance of their respective roles in providing coordinated quality care for these patients. Nurses in these departments must have knowledge of the procedure, radiation safety, and common side effects related to the implant

  3. Genome-wide association study of prostate cancer-specific survival

    DEFF Research Database (Denmark)

    Szulkin, Robert; Karlsson, Robert; Whitington, Thomas

    2015-01-01

    BACKGROUND: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical. METHODS: We performed a genome-wide survival analysis of cause-specific death in 24,...

  4. Epigenetic targets in the diagnosis and treatment of prostate cancer

    Directory of Open Access Journals (Sweden)

    Murugesan Manoharan

    2007-02-01

    Full Text Available Prostate cancer (PC is one of leading cause of cancer related deaths in men. Various aspects of cancer epigenetics are rapidly evolving and the role of 2 major epigenetic changes including DNA methylation and histone modifications in prostate cancer is being studied widely. The epigenetic changes are early event in the cancer development and are reversible. Novel epigenetic markers are being studied, which have the potential as sensitive diagnostic and prognostic marker. Variety of drugs targeting epigenetic changes are being studied, which can be effective individually or in combination with other conventional drugs in PC treatment. In this review, we discuss epigenetic changes associated with PC and their potential diagnostic and therapeutic applications including future areas of research.

  5. Prostatic specific antigen for prostate cancer detection

    Directory of Open Access Journals (Sweden)

    Lucas Nogueira

    2009-10-01

    Full Text Available Prostate-specific antigen (PSA has been used for prostate cancer detection since 1994. PSA testing has revolutionized our ability to diagnose, treat, and follow-up patients. In the last two decades, PSA screening has led to a substantial increase in the incidence of prostate cancer (PC. This increased detection caused the incidence of advanced-stage disease to decrease at a dramatic rate, and most newly diagnosed PC today are localized tumors with a high probability of cure. PSA screening is associated with a 75% reduction in the proportion of men who now present with metastatic disease and a 32.5% reduction in the age-adjusted prostate cancer mortality rate through 2003. Although PSA is not a perfect marker, PSA testing has limited specificity for prostate cancer detection, and its appropriate clinical application remains a topic of debate. Due to its widespread use and increased over-detection, the result has been the occurrence of over-treatment of indolent cancers. Accordingly, several variations as regards PSA measurement have emerged as useful adjuncts for prostate cancer screening. These procedures take into consideration additional factors, such as the proportion of different PSA isoforms (free PSA, complexed PSA, pro-PSA and B PSA, the prostate volume (PSA density, and the rate of change in PSA levels over time (PSA velocity or PSA doubling time. The history and evidence underlying each of these parameters are reviewed in the following article.

  6. Prostatic specific antigen for prostate cancer detection.

    Science.gov (United States)

    Nogueira, Lucas; Corradi, Renato; Eastham, James A

    2009-01-01

    Prostate-specific antigen (PSA) has been used for prostate cancer detection since 1994. PSA testing has revolutionized our ability to diagnose, treat, and follow-up patients. In the last two decades, PSA screening has led to a substantial increase in the incidence of prostate cancer (PC). This increased detection caused the incidence of advanced-stage disease to decrease at a dramatic rate, and most newly diagnosed PC today are localized tumors with a high probability of cure. PSA screening is associated with a 75% reduction in the proportion of men who now present with metastatic disease and a 32.5% reduction in the age-adjusted prostate cancer mortality rate through 2003. Although PSA is not a perfect marker, PSA testing has limited specificity for prostate cancer detection, and its appropriate clinical application remains a topic of debate. Due to its widespread use and increased over-detection, the result has been the occurrence of over-treatment of indolent cancers. Accordingly, several variations as regards PSA measurement have emerged as useful adjuncts for prostate cancer screening. These procedures take into consideration additional factors, such as the proportion of different PSA isoforms (free PSA, complexed PSA, pro-PSA and B PSA), the prostate volume (PSA density), and the rate of change in PSA levels over time (PSA velocity or PSA doubling time). The history and evidence underlying each of these parameters are reviewed in the following article.

  7. Men's perspectives of prostate cancer screening: A systematic review of qualitative studies.

    Directory of Open Access Journals (Sweden)

    Laura J James

    Full Text Available Prostate cancer is the most commonly diagnosed non-skin cancer in men. Screening for prostate cancer is widely accepted; however concerns regarding the harms outweighing the benefits of screening exist. Although patient's play a pivotal role in the decision making process, men may not be aware of the controversies regarding prostate cancer screening. Therefore we aimed to describe men's attitudes, beliefs and experiences of prostate cancer screening.Systematic review and thematic synthesis of qualitative studies on men's perspectives of prostate cancer screening. Electronic databases and reference lists were searched to October 2016.Sixty studies involving 3,029 men aged from 18-89 years, who had been screened for prostate cancer by Prostate Specific Antigen (PSA or Digital Rectal Examination (DRE and not screened, across eight countries were included. Five themes were identified: Social prompting (trusting professional opinion, motivation from family and friends, proximity and prominence of cancer; gaining decisional confidence (overcoming fears, survival imperative, peace of mind, mental preparation, prioritising wellbeing; preserving masculinity (bodily invasion, losing sexuality, threatening manhood, medical avoidance; avoiding the unknown and uncertainties (taboo of cancer-related death, lacking tangible cause, physiological and symptomatic obscurity, ambiguity of the procedure, confusing controversies; and prohibitive costs.Men are willing to participate in prostate cancer screening to prevent cancer and gain reassurance about their health, particularly when supported or prompted by their social networks or healthcare providers. However, to do so they needed to mentally overcome fears of losing their masculinity and accept the intrusiveness of screening, the ambiguities about the necessity and the potential for substantial costs. Addressing the concerns and priorities of men may facilitate informed decisions about prostate cancer screening

  8. Pre-diagnostic metabolite concentrations and prostate cancer risk in 1077 cases and 1077 matched controls in the European Prospective Investigation into Cancer and Nutrition.

    NARCIS (Netherlands)

    Schmidt, Julie A; Fensom, Georgina K; Rinaldi, Sabina; Scalbert, Augustin; Appleby, Paul N; Achaintre, David; Gicquiau, Audrey; Gunter, Marc J; Ferrari, Pietro; Kaaks, Rudolf; Kühn, Tilman; Floegel, Anna; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Anifantis, Eleutherios; Agnoli, Claudia; Palli, Domenico; Trevisan, Morena; Tumino, Rosario; Bueno-de-Mesquita, H Bas; Agudo, Antonio; Larrañaga, Nerea; Redondo-Sánchez, Daniel; Barricarte, Aurelio; Huerta, José Maria; Quirós, J Ramón; Wareham, Nick; Khaw, Kay-Tee; Perez-Cornago, Aurora; Johansson, Mattias; Cross, Amanda J; Tsilidis, Konstantinos K; Riboli, Elio; Key, Timothy J; Travis, Ruth C

    2017-01-01

    Little is known about how pre-diagnostic metabolites in blood relate to risk of prostate cancer. We aimed to investigate the prospective association between plasma metabolite concentrations and risk of prostate cancer overall, and by time to diagnosis and tumour characteristics, and risk of death

  9. Anti-cancer effect of bee venom in prostate cancer cells through activation of caspase pathway via inactivation of NF-κB.

    Science.gov (United States)

    Park, Mi Hee; Choi, Myoung Suk; Kwak, Dong Hoon; Oh, Ki-Wan; Yoon, Do Young; Han, Sang Bae; Song, Ho Sueb; Song, Min Jong; Hong, Jin Tae

    2011-06-01

    Bee venom has been used as a traditional medicine to treat arthritis, rheumatism, back pain, cancerous tumors, and skin diseases. However, the effects of bee venom on the prostate cancer and their action mechanisms have not been reported yet. To determine the effect of bee venom and its major component, melittin on the prostate cancer cells, apoptosis is analyzed by tunnel assay and apoptotic gene expression. For xenograft studies, bee venom was administrated intraperitoneally twice per week for 4 weeks, and the tumor growth was measured and the tumor were analyzed by immunohistochemistry. To investigate whether bee venom and melittin can inactivate nuclear factor kappa B (NF-κB), we assessed NF-κB activity in vitro and in vivo. Bee venom (1-10 µg/ml) and melittin (0.5-2.5 µg/ml) inhibited cancer cell growth through induction of apoptotic cell death in LNCaP, DU145, and PC-3 human prostate cancer cells. These effects were mediated by the suppression of constitutively activated NF-κB. Bee venom and melittin decreased anti-apoptotic proteins but induced pro-apoptotic proteins. However, pan caspase inhibitor abolished bee venom and melittin-induced apoptotic cell death and NF-κB inactivation. Bee venom (3-6 mg/kg) administration to nude mice implanted with PC-3 cells resulted in inhibition of tumor growth and activity of NF-κB accompanied with apoptotic cell death. Therefore, these results indicated that bee venom and melittin could inhibit prostate cancer in in vitro and in vivo, and these effects may be related to NF-κB/caspase signal mediated induction of apoptotic cell death. Copyright © 2010 Wiley-Liss, Inc.

  10. Other biomarkers for detecting prostate cancer.

    Science.gov (United States)

    Nogueira, Lucas; Corradi, Renato; Eastham, James A

    2010-01-01

    Prostate-specific antigen (PSA) has been used for detecting prostate cancer since 1994. Although it is the best cancer biomarker available, PSA is not perfect. It lacks both the sensitivity and specificity to accurately detect the presence of prostate cancer. None of the PSA thresholds currently in use consistently identify patients with prostate cancer and exclude patients without cancer. Novel approaches to improve our ability to detect prostate cancer and predict the course of the disease are needed. Additional methods for detecting prostate cancer have been evaluated. Despite the discovery of many new biomarkers, only a few have shown some clinical value. These markers include human kallikrein 2, urokinase-type plasminogen activator receptor, prostate-specific membrane antigen, early prostate cancer antigen, PCA3, alpha-methylacyl-CoA racemase and glutathione S-transferase pi hypermethylation. We review the reports on biomarkers for prostate cancer detection, and their possible role in the clinical practice.

  11. Targeting Quiescence in Prostate Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0413 TITLE: Targeting Quiescence in Prostate Cancer PRINCIPAL INVESTIGATOR: Laura Buttitta CONTRACTING...Quiescence in Prostate Cancer 5a. CONTRACT NUMBER Targeting uiescence in Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0413 5c. PROGRAM ELEMENT NUMBER 6...NOTES 14. ABSTRACT A major problem in prostate cancer is finding and eliminating the non-proliferating or “quiescent” cancer cells. This is because early

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

    Science.gov (United States)

    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

  13. Biomarkers in Prostate Cancer Epidemiology

    Directory of Open Access Journals (Sweden)

    Mudit Verma

    2011-09-01

    Full Text Available Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person’s genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed.

  14. Prostate cancer staging

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000397.htm Prostate cancer staging To use the sharing features on this ... trials you may be able to join How Prostate Cancer Staging is Done Initial staging is based on ...

  15. Prostate Cancer Screening

    Science.gov (United States)

    ... treat. There is no standard screening test for prostate cancer. Researchers are studying different tests to find those ... PSA level may be high if you have prostate cancer. It can also be high if you have ...

  16. The Early Prostate Cancer program: bicalutamide in nonmetastatic prostate cancer

    DEFF Research Database (Denmark)

    Iversen, Peter; Roder, Martin Andreas; Røder, Martin Andreas

    2008-01-01

    The Early Prostate Cancer program is investigating the addition of bicalutamide 150 mg to standard care for localized or locally advanced, nonmetastatic prostate cancer. The third program analysis, at 7.4 years' median follow-up, has shown that bicalutamide 150 mg does not benefit patients...

  17. Molecular Basis of the Anti-Cancer Effects of Genistein Isoflavone in LNCaP Prostate Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Hartmann J

    2011-03-01

    Full Text Available Background: Prostate cancer is the most common form of non-skin cancer within the United States and the second leading cause of cancer deaths. Survival rates for the advanced disease remain relatively low, and conventional treatments may be accompanied by significant side effects. As a result, current research is aimed at alternative or adjuvant treatments that will target components of the signal transduction, cell-cycle and apoptosis pathways, to induce cell death with little or no toxic side effects to the patient. In this study, we investigated the effect of genistein isoflavone, a soy derivative, on expression levels of genes involved in these pathways. The mechanism of genistein-induced cell death was also investigated. The chemosensitivity of the LNCaP prostate cancer cells to genistein was investigated using ATP and MTS assays, and a caspase binding assay was used to determine apoptosis induction. Several molecular targets were determined using cDNA microarray and RT-PCR analysis.Results: The overall data revealed that genistein induces cell death in a time- and dose-dependent manner, and regulates expression levels of several genes involved in carcinogenesis and immunity. Several cell-cycle genes were down-regulated, including the mitotic kinesins, cyclins and cyclin-dependent kinases. Various members of the Bcl-2 family of apoptotic proteins were also affected. The DefB1 and the HLA membrane receptor genes involved in immunogenicity were also up-regulated.Conclusion: The results indicate that genistein inhibits growth of the hormone-dependent prostate cancer cells, LNCaP, via apoptosis induction through regulation of some of the genes involved in carcinogenesis of many tumors, and immunogenicity. This study augments the potential phytotherapeutic and immunotherapeutic significance of genistein isoflavone.

  18. An assessment of Prostate Cancer Research International: Active Surveillance (PRIAS) criteria for active surveillance of clinically low-risk prostate cancer patients

    Science.gov (United States)

    da Silva, Vitor; Cagiannos, Ilias; Lavallée, Luke T.; Mallick, Ranjeeta; Witiuk, Kelsey; Cnossen, Sonya; Eastham, James A.; Fergusson, Dean A.; Morash, Chris; Breau, Rodney H.

    2017-01-01

    Introduction Active surveillance is a strategy to delay or prevent treatment of indolent prostate cancer. The Prostate Cancer Research International: Active Surveillance (PRIAS) criteria were developed to select patients for prostate cancer active surveillance. The objective of this study was to compare pathological findings from PRIAS-eligible and PRIAS-ineligible clinically low-risk prostate cancer patients. Methods A D’Amico low-risk cohort of 1512 radical prostatectomy patients treated at The Ottawa Hospital or Memorial Sloan Kettering Cancer Centre between January 1995 and December 2007 was reviewed. Pathological outcomes (pT3 tumours, Gleason sum ≥7, lymph node metastases, or a composite) and clinical outcomes (prostate-specific antigen [PSA] recurrence, secondary cancer treatments, and death) were compared between PRIAS-eligible and PRIAS-ineligible cohorts. Results The PRIAS-eligible cohort (n=945) was less likely to have Gleason score ≥7 (odds ratio [OR] 0.61; 95% confidence interval [CI] 0.49–0.75), pT3 (OR 0.41; 95% CI 0.31–0.55), nodal metastases (OR 0.37; 95% CI 0.10–1.31), or any adverse feature (OR 0.56; 95% CI 0.45–0.69) compared to the PRIAS-ineligible cohort. The probability of any adverse pathology in the PRIAS-eligible cohort was 41% vs. 56% in the PRIAS-ineligible cohort. At median follow-up of 3.7 years, 72 (4.8%) patients had a PSA recurrence, 24 (1.6%) received pelvic radiation, and 13 (0.9%) received androgen deprivation. No difference was detected for recurrence-free and overall survival between groups (recurrence hazard ratio [HR] 0.71; 95% CI 0.46–1.09 and survival HR 0.72; 95% CI 0.36–1.47). Conclusions Low-risk prostate cancer patients who met PRIAS eligibility criteria are less likely to have higher-risk cancer compared to those who did not meet at least one of these criteria. PMID:28798822

  19. Early prostate cancer antigen expression in predicting presence of prostate cancer in men with histologically negative biopsies.

    Science.gov (United States)

    Hansel, D E; DeMarzo, A M; Platz, E A; Jadallah, S; Hicks, J; Epstein, J I; Partin, A W; Netto, G J

    2007-05-01

    Early prostate cancer antigen is a nuclear matrix protein that was recently shown to be expressed in prostate adenocarcinoma and adjacent benign tissue. Previous studies have demonstrated early prostate cancer antigen expression in benign prostate tissue up to 5 years before a diagnosis of prostate carcinoma, suggesting that early prostate cancer antigen could be used as a potential predictive marker. We evaluated early prostate cancer antigen expression by immunohistochemistry using a polyclonal antibody (Onconome Inc., Seattle, Washington) on benign biopsies from 98 patients. Biopsies were obtained from 4 groups that included 39 patients with first time negative biopsy (group 1), 24 patients with persistently negative biopsies (group 2), 8 patients with initially negative biopsies who were subsequently diagnosed with prostate carcinoma (group 3) and negative biopsies obtained from 27 cases where other concurrent biopsies contained prostate carcinoma (group 4). Early prostate cancer antigen staining was assessed by 2 of the authors who were blind to the group of the examined sections. Staining intensity (range 0 to 3) and extent (range 1 to 3) scores were assigned. The presence of intensity 3 staining in any of the blocks of a biopsy specimen was considered as positive for early prostate cancer antigen for the primary outcome in the statistical analysis. In addition, as secondary outcomes we evaluated the data using the proportion of blocks with intensity 3 early prostate cancer antigen staining, the mean of the product of staining intensity and staining extent of all blocks within a biopsy, and the mean of the product of intensity 3 staining and extent. Primary outcome analysis revealed the proportion of early prostate cancer antigen positivity to be highest in group 3 (6 of 8, 75%) and lowest in group 2 (7 of 24, 29%, p=0.04 for differences among groups). A relatively higher than expected proportion of early prostate cancer antigen positivity was present in

  20. From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

    International Nuclear Information System (INIS)

    Thobe, Megan N.; Clark, Robert J.; Bainer, Russell O.; Prasad, Sandip M.; Rinker-Schaeffer, Carrie W.

    2011-01-01

    Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1) characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2) chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3) current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies

  1. From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Thobe, Megan N. [Section of Urology, Department of Surgery, The University of Chicago, Chicago, IL 60637 (United States); Clark, Robert J. [Department of Molecular Pathogenesis and Molecular Medicine, The University of Chicago, Chicago, IL 60637 (United States); Bainer, Russell O. [Department of Human Genetics, The University of Chicago, Chicago, IL 60637 (United States); Prasad, Sandip M.; Rinker-Schaeffer, Carrie W., E-mail: crinkers@uchicago.edu [Section of Urology, Department of Surgery, The University of Chicago, Chicago, IL 60637 (United States)

    2011-01-27

    Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1) characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2) chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3) current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies.

  2. Current Challenges in Prostate Cancer Management and the Rationale behind Targeted Focal Therapy

    Directory of Open Access Journals (Sweden)

    Al B. Barqawi

    2012-01-01

    Full Text Available Among men, prostate cancer has a high prevalence, with relatively lower cancer-specific mortality risk compared to lung and colon cancer. Prostate-specific antigen (PSA screening has increased prostate cancer awareness since its implementation as a screening tool almost 25 years ago, but, due to the largely indolent course of this disease and the unspecific nature of the PSA test, increased incidence has largely been associated with cancers that would not go on to cause death (clinically insignificant, leading to an overdiagnosis challenge and an ensuing overtreatment consequences. The overtreatment problem is exacerbated by the high risk of side effects that current treatment techniques have, putting patients’ quality of life at risk with little or no survival benefit. The goals of this paper are to evaluate the rise, prevalence, and impact of the overdiagnosis and ensuing overtreatment problems, as well as highlight potential solutions. In this effort, a review of major epidemiological and screening studies, cancer statistics from the advent of prostate-specific antigen screening to the present, and reports on patient concerns and treatment outcomes was conducted to present the dominant factors that underlie current challenges in prostate cancer treatment and illuminate potential solutions.

  3. Abiraterone acetate: oral androgen biosynthesis inhibitor for treatment of castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Rosenberg JE

    2012-01-01

    Full Text Available Yasser Rehman1, Jonathan E Rosenberg21Division of Hospital Medicine, UMass Memorial Healthcare, Worcester, MA, USA; 2Lank Center for Genitourinary Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USAAbstract: Prostate cancer is the second leading cause of cancer death in men in the US and Europe. The treatment of advanced-stage prostate cancer has been androgen deprivation. Medical castration leads to decreased production of testosterone and dihydrotestosterone by the testes, but adrenal glands and even prostate cancer tissue continue to produce androgens, which eventually leads to continued prostate cancer growth despite castrate level of androgens. This stage is known as castrate-resistant prostate cancer (CRPC, which continues to be a challenge to treat. Addition of androgen antagonists to hormonal deprivation has been successful in lowering the prostate-specific antigen levels further, but has not actually translated into life-prolonging options. The results of several contemporary studies have continued to demonstrate activation of the androgen receptor as being the key factor in the continued growth of prostate cancer. Blockade of androgen production by nongonadal sources has led to clinical benefit in this setting. One such agent is abiraterone acetate, which significantly reduces androgen production by blocking the enzyme, cytochrome P450 17 alpha-hydroxylase (CYP17. This has provided physicians with another treatment option for patients with CRPC. The landscape for prostate cancer treatment has changed with the approval of cabazitaxel, sipuleucel-T and abiraterone. Here we provide an overview of abiraterone acetate, its mechanism of action, and its potential place for therapy in CRPC.Keywords: CRPC, abiraterone, CYP17, inhibitors, androgens, castration resistant prostate cancer

  4. Comparison of sonographic features in benign prostate hyperplasia and prostate cancer

    International Nuclear Information System (INIS)

    Choi, Won Young; Hong, Hyun Sook; Kang, Eun Young; Seol, Hae Young; Suh, Won Hyuck

    1988-01-01

    Transrectal sonography of prostate was sensitive to textural changes produced by both benign prostate hyperplasia (BPH) and prostate cancers. During recent 4 years, twenty cases of BPH and twenty cases of prostate cancers proven histologically were analyzed in their sonographic features, retrospectively, by using transrectal prostate sonography and suprapubic prostate sonography. The results were as follows: 1. Mean weights of BPH and prostate cancers was 40.4g and 47.6g, respectively. 2. Sonographic features of BPH revealed isoechogenecity in 11 cases, homogeneity in 18 cases, well defined capsular margins in 19 cases, and calcification in 16 cases. 3. Sonographic features of prostate cancers revealed mixed echogenecity in 14 cases, inhomogeneity in 15 cases, poorly defined capsular margin in 14 cases, and calcifications in 13 cases. 4. Authors concluded that prostate sonography were valuable diagnostic modality in the differentiation of BPH and prostate cancers.

  5. Management Options in Advanced Prostate Cancer: What is the Role for Sipuleucel-T?

    OpenAIRE

    Bitting, Rhonda L.; Armstrong, Andrew J.; George, Daniel J.

    2011-01-01

    Most prostate cancer-related deaths occur in patients with castration-resistant prostate cancer (CRPC). Until recently, only therapy with docetaxel and prednisone has been shown to prolong survival in men with metastatic CRPC. With the United States Food and Drug Administration (US FDA) approvals of sipuleucel-T, cabazitaxel, and abiraterone acetate, all based on improvement in overall survival, the landscape for management of men with metastatic CRPC has dramatically changed. In this review ...

  6. Targeting MTA1/HIF-1alpha Signaling by Pterostilbene in Combination with Histone Deacetylase Inhibitor Attenuates Prostate Cancer Progression (Open Access)

    Science.gov (United States)

    2017-08-30

    expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer cell proliferation. Mol. Cancer Ther. 6:51–60. 25...2673 Introduction Prostate cancer (PCa) is the second most common cause of cancer - related death in men in the USA because of advanced castrate...signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression Nasir A. Butt1,2, Avinash Kumar1,3

  7. Genistein and daidzein: different molecular effects on prostate cancer.

    Science.gov (United States)

    Adjakly, Mawussi; Ngollo, Marjolaine; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

    2013-01-01

    Diet is believed to play an important role in cancer. It has been revealed by epidemiological studies that Asian populations, who consume phytoestrogens in large amounts, have a lower incidence of prostate cancer in comparison with the Western world, where consumption of soy is lower. Genistein and daidzein, the soy phytoestrogens most widely studied, are believed to be potent anticancer agents and have been shown to possess anticancer properties. It has been shown that these compounds inhibit the growth of cancer cells through the modulation of genes controlling cell-cycle progression. Genistein inhibits the activation of the kappa light polypeptide gene enhancer in B-cells (NF-κB), signaling pathway, which is implicated in the balance between cell survival and programmed cell death (apoptosis). Antioxidant and antiangiogenesis properties of genistein have been also described. Soy isoflavones are also implicated in reversion of epigenetic events observed in prostate cancer. Significant advances have been made for understanding how soy isoflavones are implicated in protection against prostate cancer. However, more studies are needed to better-understand and elucidate all pathways mobilized by genistein and daidzein, in order to fully exploit their anticancer properties.

  8. Duration of short-course androgen suppression therapy and the risk of death as a result of prostate cancer.

    LENUS (Irish Health Repository)

    D'Amico, Anthony V

    2011-12-10

    We evaluated whether the duration of androgen suppression therapy (AST) had an impact on the risk of prostate cancer-specific mortality (PCSM) in men with unfavorable-risk prostate cancer (PC) within established Gleason score (GS) categories.

  9. Precision medicine for advanced prostate cancer.

    Science.gov (United States)

    Mullane, Stephanie A; Van Allen, Eliezer M

    2016-05-01

    Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients.

  10. Prostate cancer

    DEFF Research Database (Denmark)

    Chabanova, Elizaveta; Balslev, Ingegerd; Logager, Vibeke

    2011-01-01

    To investigate diagnostic accuracy of detection of prostate cancer by magnetic resonance: to evaluate the performance of T2WI, DCEMRI and CSI and to correlate the results with biopsy and radical prostatectomy histopathological data.......To investigate diagnostic accuracy of detection of prostate cancer by magnetic resonance: to evaluate the performance of T2WI, DCEMRI and CSI and to correlate the results with biopsy and radical prostatectomy histopathological data....

  11. On cribriform prostate cancer

    OpenAIRE

    Kweldam, Charlotte

    2018-01-01

    markdownabstractThis general aim of the thesis is to study the clinical relevance, interobserver reproducibility, and genetics of cribriform growth in prostate cancer. More specifically, the aims and outline of this thesis are • To study the metastatic potential of modified Gleason score 3+3 prostate cancer in radical prostatectomies. (Chapter 2) • To examine the prognostic value of individual Gleason grade 4 patterns in prostate cancer in radical prostatectomy and diagnostic biopsy specimens...

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

    Science.gov (United States)

    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.

  13. Epigenetic Regulation in Prostate Cancer Progression.

    Science.gov (United States)

    Ruggero, Katia; Farran-Matas, Sonia; Martinez-Tebar, Adrian; Aytes, Alvaro

    2018-01-01

    An important number of newly identified molecular alterations in prostate cancer affect gene encoding master regulators of chromatin biology epigenetic regulation. This review will provide an updated view of the key epigenetic mechanisms underlying prostate cancer progression, therapy resistance, and potential actionable mechanisms and biomarkers. Key players in chromatin biology and epigenetic master regulators has been recently described to be crucially altered in metastatic CRPC and tumors that progress to AR independency. As such, epigenetic dysregulation represents a driving mechanism in the reprograming of prostate cancer cells as they lose AR-imposed identity. Chromatin integrity and accessibility for transcriptional regulation are key features altered in cancer progression, and particularly relevant in nuclear hormone receptor-driven tumors like prostate cancer. Understanding how chromatin remodeling dictates prostate development and how its deregulation contributes to prostate cancer onset and progression may improve risk stratification and treatment selection for prostate cancer patients.

  14. Minnelide Inhibits Androgen Dependent, Castration Resistant Prostate Cancer Growth by Decreasing Expression of Androgen Receptor Full Length and Splice Variants.

    Science.gov (United States)

    Isharwal, Sumit; Modi, Shrey; Arora, Nivedita; Uhlrich, Charles; Giri, Bhuwan; Barlass, Usman; Soubra, Ayman; Chugh, Rohit; Dehm, Scott M; Dudeja, Vikas; Saluja, Ashok; Banerjee, Sulagna; Konety, Badrinath

    2017-05-01

    With almost 30,000 deaths per year, prostate cancer is the second-leading cause of cancer-related death in men. Androgen Deprivation Therapy (ADT) has been the corner stone of prostate cancer treatment for decades. However, despite an initial response of prostate cancer to ADT, this eventually fails and the tumors recur, resulting in Castration Resistant Prostate Cancer (CRPC). Triptolide, a diterpene triepoxide, has been tested for its anti-tumor properties in a number of cancers for over a decade. Owing to its poor solubility in aqueous medium, its clinical application had been limited. To circumvent this problem, we have synthesized a water-soluble pro-drug of triptolide, Minnelide, that is currently being evaluated in a Phase 1 clinical trial against gastrointestinal tumors. In the current study, we assessed the therapeutic potential of Minnelide and its active compound triptolide against androgen dependent prostate cancer both in vitro as well as in vivo. Cell viability was measured by a MTT based assay after treating prostate cancer cells with multiple doses of triptolide. Apoptotic cell death was measured using a caspase 3/7 activity. Androgen Receptor (AR) promoter-binding activity was evaluated by using luciferase reporter assay. For evaluating the effect in vivo, 22Rv1 cells were implanted subcutaneously in animals, following which, treatment was started with 0.21 mg/kg Minnelide. Our study showed that treatment with triptolide induced apoptotic cell death in CRPC cells. Triptolide treatment inhibited AR transcriptional activity and decreased the expression of AR and its splice variants both at the mRNA and the protein level. Our studies show that triptolide inhibits nuclear translocation of Sp1, resulting in its decreased transcriptional activity leading to downregulation of AR and its splice variants in prostate cancer cells. In vivo, Minnelide (0.21 mg/kg) regressed subcutaneous tumors derived from CRPC 22RV1 at our study endpoint. Our animal

  15. Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm.

    Science.gov (United States)

    Vargas, Hebert Alberto; Grimm, Jan; F Donati, Olivio; Sala, Evis; Hricak, Hedvig

    2015-05-01

    The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. • Advanced imaging techniques allow direct visualisation of molecular interactions in prostate cancer. • MRI/PET, optical and Cerenkov imaging facilitate the translation of molecular biology. • Multiple compounds targeting PSMA expression are currently undergoing clinical translation. • Other targets (e.g., PSA, prostate-stem cell antigen, GRPR) are in development.

  16. Comparison of telomerase activity in prostate cancer, prostatic intraepithelial neoplasia and benign prostatic hyperplasia

    Directory of Open Access Journals (Sweden)

    Soleiman Mahjoub

    2006-11-01

    Full Text Available BACKGROUND: Telomerase is a reverse transcriptase enzyme that synthesizes telomeric DNA on chromosome ends. The enzyme is important for the immortalization of cancer cells because it maintains the telomeres. METHODS: Telomerase activity (TA was measured by fluorescence-based telomeric repeat amplification protocol (FTRAP assay in prostate carcinoma and benign prostatic hyperplasia (BPH. RESULTS: TA was present in 91.4% of 70 prostate cancers, 68.8% of 16 prostatic intraepithelial neoplasia (PIN, 43.3% of 30 BPH*, 21.4% of 14 atrophy and 20% of 15 normal samples adjacent to tumor. There was not any significant correlation between TA, histopathological tumor stage or gleason score. In contrast to high TA in the BPH* tissue from the cancer-bearing gland, only 6.3% of 32 BPH specimens from patients only diagnosed with BPH were telomerase activity-positive. CONCLUSIONS: These results indicate that TA is present in most prostate cancers. The high rate of TA in tissue adjacent to tumor may be attributed either to early molecular alteration of cancer that was histologically unapparent, or to the presence of occult cancer cells. Our findings suggest that the re-expression of telomerase activity could be one step in the transformation of BPH to PIN. KEY WORDS: Telomerase activity, prostate cancer, prostatic intraepithelial neoplasia, benign prostatic hyperplasia.

  17. Targeting fibroblast growth factor receptor signaling inhibits prostate cancer progression.

    Science.gov (United States)

    Feng, Shu; Shao, Longjiang; Yu, Wendong; Gavine, Paul; Ittmann, Michael

    2012-07-15

    Extensive correlative studies in human prostate cancer as well as studies in vitro and in mouse models indicate that fibroblast growth factor receptor (FGFR) signaling plays an important role in prostate cancer progression. In this study, we used a probe compound for an FGFR inhibitor, which potently inhibits FGFR-1-3 and significantly inhibits FGFR-4. The purpose of this study is to determine whether targeting FGFR signaling from all four FGFRs will have in vitro activities consistent with inhibition of tumor progression and will inhibit tumor progression in vivo. Effects of AZ8010 on FGFR signaling and invasion were analyzed using immortalized normal prostate epithelial (PNT1a) cells and PNT1a overexpressing FGFR-1 or FGFR-4. The effect of AZ8010 on invasion and proliferation in vitro was also evaluated in prostate cancer cell lines. Finally, the impact of AZ8010 on tumor progression in vivo was evaluated using a VCaP xenograft model. AZ8010 completely inhibits FGFR-1 and significantly inhibits FGFR-4 signaling at 100 nmol/L, which is an achievable in vivo concentration. This results in marked inhibition of extracellular signal-regulated kinase (ERK) phosphorylation and invasion in PNT1a cells expressing FGFR-1 and FGFR-4 and all prostate cancer cell lines tested. Treatment in vivo completely inhibited VCaP tumor growth and significantly inhibited angiogenesis and proliferation and increased cell death in treated tumors. This was associated with marked inhibition of ERK phosphorylation in treated tumors. Targeting FGFR signaling is a promising new approach to treating aggressive prostate cancer.

  18. Prostate cancer and inflammation: the evidence

    Science.gov (United States)

    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

  19. [Prostate cancer patients with lymph node metastasis. Outcome in a consecutive group of 59 patients

    DEFF Research Database (Denmark)

    Roder, M.A.; Reinhardt, S.; Brasso, K.

    2008-01-01

    INTRODUCTION: The optimal management of prostate cancer patients with lymph node metastasis remains controversial. In this article, the outcome in a consecutive group of patients with newly diagnosed lymph node positive prostate cancer is presented. MATERIALS AND METHODS: In 59 patients...... with histological verified lymph node positive disease but without osseous metastasis, outcome is described by time to biochemical progression, time to metastasis and survival. RESULTS: Median age at diagnosis was 62 years. Median pre-treatment PSA was 21 ng/ml. Endocrine treatment was initiated within median 2...... patients died during follow-up, 15 deaths were attributable to prostate cancer. Estimated median survival was 5.5 years. CONCLUSION: Despite early androgen deprivation therapy, patients with lymph node positive prostate cancer have a grave prognosis with a high risk of progression and disease...

  20. MRI diagnosis for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tamada, Tsutomu; Nagai, Kiyohisa; Imai, Shigeki; Kajihara, Yasumasa; Jo, Yoshimasa; Tanaka, Hiroyoshi; Fukunaga, Masao (Kawasaki Medical School, Kurashiki, Okayama (Japan)); Matsuki, Takakazu

    1998-01-01

    Recently, in Japan, both the Westernization of life styles and the advent of an aged-society have led to an increase in the incidence of prostate cancer. In making a localizing diagnosis of prostate cancer, magnetic resonance imaging (MRI), which has excellent contrast resolution, and transrectal ultrasonography, are used clinically, and their usefulness is being established. MRI is employed in the diagnosis of prostate cancer to detect tumors, and to determine the stage of such tumors. For the visualization of prostate cancer by MRI, T2-weighted axial images are used exclusively. After becoming familiar with normal prostate images, it is important to evaluate the localization of a tumor, and the invasion of the capsule and seminal vesicles. Future applications of new techniques for MRI will undoubtedly be found. In this paper, the present state of MRI diagnosis of prostate cancer at Kawasaki Medical School Hospital will be reviewed. (author)

  1. MRI diagnosis for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tamada, Tsutomu; Nagai, Kiyohisa; Imai, Shigeki; Kajihara, Yasumasa; Jo, Yoshimasa; Tanaka, Hiroyoshi; Fukunaga, Masao [Kawasaki Medical School, Kurashiki, Okayama (Japan); Matsuki, Takakazu

    1998-12-31

    Recently, in Japan, both the Westernization of life styles and the advent of an aged-society have led to an increase in the incidence of prostate cancer. In making a localizing diagnosis of prostate cancer, magnetic resonance imaging (MRI), which has excellent contrast resolution, and transrectal ultrasonography, are used clinically, and their usefulness is being established. MRI is employed in the diagnosis of prostate cancer to detect tumors, and to determine the stage of such tumors. For the visualization of prostate cancer by MRI, T2-weighted axial images are used exclusively. After becoming familiar with normal prostate images, it is important to evaluate the localization of a tumor, and the invasion of the capsule and seminal vesicles. Future applications of new techniques for MRI will undoubtedly be found. In this paper, the present state of MRI diagnosis of prostate cancer at Kawasaki Medical School Hospital will be reviewed. (author)

  2. Baldness, benign prostate hyperplasia, prostate cancer and androgen levels.

    Science.gov (United States)

    Faydaci, Gökhan; Bilal, Eryildirim; Necmettin, Penpegül; Fatih, Tarhan; Asuman, Orçun; Uğur, Kuyumcuoğlu

    2008-12-01

    We evaluated the pattern of baldness and serum androgen levels in patients with benign prostate hyperplasia (BPH) and prostate cancer. BPH, prostate cancer and androgenic alopecia (AA) were somehow androgen dependent and affect large population of elderly men. A total of 152 patients, 108 patients with BPH and 44 patients with prostate cancer were included in the study. We measured serum total, free and bioavailable testosterone, FSH, LH, prolactin, estradiol, albumin and SHBG levels. Baldness classification was based on Norwood's classification and we categorised baldness as vertex and frontal baldness. The frequency of AA in BPH and prostate cancer groups were not different. We looked for some correlation between the two groups with respect to AA and hormone levels. We did not find any correlation between AA and total testosterone, free testosterone, bioavailable testosterone or SHBG levels in both groups. This prospective study with selected small group of patients showed that there is no difference of male pattern baldness in BPH and prostate cancer patients and also there is no correlation between pattern of baldness and serum androgen levels.

  3. Evaluation of inflammatory cytokines and oxidative stress markers in prostate cancer patients undergoing curative radiotherapy

    Directory of Open Access Journals (Sweden)

    Phebe L. Abdel-Messeih

    2017-05-01

    Full Text Available Prostate cancer is the second leading cause of cancer-related death in men. The present study was carried out to investigate the radiation response of serum cytokines and oxidative markers to find out if these novel biomarkers have significant applications regarding radiation outcome in prostate cancer patients. Significant elevations of prostatic specific antigen (PSA, asymmetric dimethyl arginine (ADMA and nitric oxide (NO were recorded in cancer prostate patients at the time of diagnosis compared to controls. Patients were subjected to radiotherapy post prostatectomy with a total dose of 66 Gy in 33 fractions (5 sessions/week for 7 weeks. At the end of the seventh week post radiotherapy, ADMA levels were accentuated while the levels of PSA and NO were lower than before therapy. The level of inflammatory cytokines (interleukins IL-4, IL-5 and interferon-gamma in post radiation therapy patients were significantly elevated compared to both controls and prostate cancer patients. A significant inverse correlation was observed in prostate cancer patients between ADMA and NO. Moreover, a significant inverse correlation in post radiation therapy patients was observed between IL-5 and PSA. These results are highly suggestive that there is a specific cytokine response in patients undergoing curative radiotherapy for prostate cancer.

  4. Ultrasonography and prostate-specific antigen (PSA) in differential diagnosis of prostate cancer and benign prostatic hyperplasia

    International Nuclear Information System (INIS)

    Mechev, D.S.; Shcherbyina, O.V.; Yatsik, V.Yi.; Gladka, L.Yu.

    2003-01-01

    The purpose of the work is analysis of diagnostic possibilities of transrectal ultrasonography and PSA in differential diagnosis of prostate cancer and benign prostatic hyperplasia. 142 patients have been investigated by transrectal ultrasonography. he transrectal ultrasonography and PSA are sensible tests in diagnosis of prostate cancer and in differential diagnosis of benign prostatic hyperplasia and prostate cancer

  5. Transcription-Based Molecular Imaging and Gene Therapy for Castration-resistant and Metastatic Prostate Cancer in Translational Models

    OpenAIRE

    Jiang, Ziyue

    2013-01-01

    The advanced stage of prostate cancer is the second leading cause of cancer-related death for American men. Novel, effective treatment options and more cancer-specific diagnostic tools are urgently needed to facilitate patient management. Here, we explored the construction and application of an array of gene-based molecular imaging and therapeutic vectors in a variety of clinically relevant settings. These vectors exploit prostate cancer-specific promoters to control the transcription of imag...

  6. Advanced research on separating prostate cancer stem cells

    International Nuclear Information System (INIS)

    Hao Yumei; He Xin; Song Naling

    2013-01-01

    Prostate cancer is a common malignant tumor in male urinary system,and may easily develop into the hormone refractory prostate cancer which can hardly be cured. Recent studies had found that the prostate cancer stem cells may be the source of the prostate cancer's occurrence,development, metastasis and recurrence. The therapy targeting the prostate cancer stem cells may be the effective way to cure prostate cancer. But these cells is too low to be detected. The difficulty lies in the low separation efficiency of prostate cancer stem cell, so the effectively separating prostate cancer stem cells occupied the main position for the more in-depth research of prostate cancer stem cells. This paper reviews the research progress and existing problems on the several main separating methods of prostate cancer stem cells, includes the fluorescence activated cells sorting and magnetic activated cells sorting based on prostate cancer stem cell surface markers, the side-population sorting and serum-free medium sphere forming sorting based on prostate cancer stem cell's biology. (authors)

  7. Baseline prostate-specific antigen measurements and subsequent prostate cancer risk in the Danish Diet, Cancer and Health cohort

    DEFF Research Database (Denmark)

    Larsen, Signe Benzon; Brasso, Klaus; Iversen, Peter

    2013-01-01

    Although prostate-specific antigen (PSA) screening reduces mortality from prostate cancer, substantial over-diagnosis and subsequent overtreatment are concerns. Early screening of men for PSA may serve to stratify the male population by risk of future clinical prostate cancer.......Although prostate-specific antigen (PSA) screening reduces mortality from prostate cancer, substantial over-diagnosis and subsequent overtreatment are concerns. Early screening of men for PSA may serve to stratify the male population by risk of future clinical prostate cancer....

  8. Prostate Cancer: Improving the Flow of Research.

    Science.gov (United States)

    Lawton, Colleen A F

    2018-04-01

    Prostate cancer is the most common nonskin cancer diagnosed in U.S. men and kills over 27 000 men annually. Thus, improving the outcomes for patients diagnosed with this disease is imperative. There has been a considerable amount of research done over the past several decades resulting in more cures than ever, but the death rate is still unacceptable. This oration addresses the progress that we have made over the past several decades and outlines the work yet to be done, as well as some processes to make that work happen. © RSNA, 2018.

  9. Molecular diagnosis of prostate cancer: Topical issues

    Directory of Open Access Journals (Sweden)

    E. N. Knyazev

    2014-12-01

    Full Text Available Prostate cancer (PC is the second most common cancer and the fifth highest malignancy mortality rate in men worldwide. Although PC is detectable in 15-20% of men during life, its death risk is only about 3%. This means that not all PC cases require the same management tactics. The given review analyzes the current investigations searching for molecular biological markers to predict the course of PC and to choose its treatment policy, including that in the development of resistance to androgen-deprivation therapy.

  10. Immunotherapy in metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Susan F Slovin

    2016-01-01

    Full Text Available Introduction: Prostate cancer remains a challenge as a target for immunological approaches. The approval of the first cell-based immune therapy, Sipuleucel-T for prostate cancer introduced prostate cancer as a solid tumor with the potential to be influenced by the immune system. Methods: We reviewed articles on immunological management of prostate cancer and challenges that lie ahead for such strategies. Results: Treatments have focused on the identification of novel cell surface antigens thought to be unique to prostate cancer. These include vaccines against carbohydrate and blood group antigens, xenogeneic and naked DNA vaccines, and pox viruses used as prime-boost or checkpoint inhibitors. No single vaccine construct to date has resulted in a dramatic antitumor effect. The checkpoint inhibitor, anti-CTLA-4 has resulted in several long-term remissions, but phase III trials have not demonstrated an antitumor effect or survival benefit. Conclusions: Multiple clinical trials suggest that prostate cancer may not be optimally treated by single agent immune therapies and that combination with biologic agents, chemotherapies, or radiation may offer some enhancement of benefit.

  11. Role of transurethral resection of the prostate in the management of prostate cancer

    Directory of Open Access Journals (Sweden)

    Szollosi Attila

    2016-06-01

    Full Text Available Introduction: Prostate cancer is the second most diagnosed cancer in men, after lung cancer. The gold standard procedure in prostate cancer (PCa diagnosis is the ultrasound guided prostate biopsy. Transurethral resection of the prostate (TURP used in solving the bladder outlet obstruction, can have a role in detection of PCa. The aim of this retrospective study is to examine the role of transurethral resection of the prostate in the diagnosis and therapy of prostate cancer.

  12. Blood lipids and prostate cancer

    DEFF Research Database (Denmark)

    Bull, Caroline J; Bonilla, Carolina; Holly, Jeff M P

    2016-01-01

    Genetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL...... into logistic regression models to estimate the presence (and direction) of any causal effect of each lipid trait on prostate cancer risk. There was weak evidence for an association between the LDL genetic score and cancer grade: the odds ratio (OR) per genetically instrumented standard deviation (SD) in LDL.......95, 3.00; P = 0.08). The rs12916-T variant in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was inversely associated with prostate cancer (OR: 0.97; 95% CI: 0.94, 1.00; P = 0.03). In conclusion, circulating lipids, instrumented by our genetic risk scores, did not appear to alter prostate cancer risk...

  13. Cryotherapy for prostate cancer

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000907.htm Cryotherapy for prostate cancer To use the sharing features ... first treatment for prostate cancer. What Happens During Cryotherapy Before the procedure, you will be given medicine ...

  14. Amino acid containing thapsigargin analogues deplete androgen receptor protein via synthesis inhibition and induce the death of prostate cancer cells

    DEFF Research Database (Denmark)

    Griend, Donald J Vander; Antony, Lizamma; Dalrymple, Susan L

    2009-01-01

    There are quantitative and/or qualitative mechanisms allowing androgen receptor (AR) growth signaling in androgen ablation refractory prostate cancer cells. Regardless of the mechanism, agents that deplete AR protein expression prevent such AR growth signaling. Thapsigargin (TG) is a highly cell......-penetrant sequiterpene-lactone that once inside cells inhibits (IC(50), approximately 10 nmol/L) critically important housekeeping SERCA 2b calcium pumps in the endoplasmic reticulum. Using a series of five genetically diverse androgen ablation refractory human prostate cancer lines (LNCaP, LAPC-4, VCaP, MDA-PCa-2b......-specific proteases, such as prostate-specific antigen and prostate-specific membrane antigen, or cancer-specific proteases, such as fibroblast activation protein, so that toxicity of these prodrugs is selectively targeted to metastatic sites of prostate cancer. Based on these results, these prodrugs are undergoing...

  15. Vitamin D in prostate cancer

    Directory of Open Access Journals (Sweden)

    Donald L Trump

    2018-01-01

    Full Text Available Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signaling may be important in the cause and prognosis of prostate and other cancers. These data indicate that perturbation of vitamin D signaling may be a target for the prevention and treatment of prostate cancer. Large studies of vitamin D supplementation will be required to determine whether these observations can be translated into prevention strategies. This paper reviews the available data in the use of vitamin D compounds in the treatment of prostate cancer. Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer. However, clinical trials guided by existing preclinical data are limited.

  16. Vitamin D in prostate cancer.

    Science.gov (United States)

    Trump, Donald L; Aragon-Ching, Jeanny B

    2018-04-13

    Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signaling may be important in the cause and prognosis of prostate and other cancers. These data indicate that perturbation of vitamin D signaling may be a target for the prevention and treatment of prostate cancer. Large studies of vitamin D supplementation will be required to determine whether these observations can be translated into prevention strategies. This paper reviews the available data in the use of vitamin D compounds in the treatment of prostate cancer. Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer. However, clinical trials guided by existing preclinical data are limited.

  17. Vitamin D in prostate cancer

    Science.gov (United States)

    Trump, Donald L; Aragon-Ching, Jeanny B

    2018-01-01

    Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signaling may be important in the cause and prognosis of prostate and other cancers. These data indicate that perturbation of vitamin D signaling may be a target for the prevention and treatment of prostate cancer. Large studies of vitamin D supplementation will be required to determine whether these observations can be translated into prevention strategies. This paper reviews the available data in the use of vitamin D compounds in the treatment of prostate cancer. Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer. However, clinical trials guided by existing preclinical data are limited. PMID:29667615

  18. Human Prostate Cancer Hallmarks Map

    Science.gov (United States)

    Datta, Dipamoy; Aftabuddin, Md.; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

    2016-01-01

    Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process. PMID:27476486

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

    Science.gov (United States)

    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.

  20. Psychosocial and Quality of Life Issues in Prostate and Ovarian Cancer

    NARCIS (Netherlands)

    J.B. Madalinska

    2007-01-01

    textabstractProstate and ovarian cancers are among the leading causes of death in Western countries. Applied preventive health strategies, including screening and early medical treatments either with prophylactic or curative intention, may substantially affect patients’ quality of life (QOL). This

  1. [Involvement of cranial pairs as manifestation of prostatic cancer].

    Science.gov (United States)

    Ripa Saldias, L M; Ayuso Blanco, T; Delpon Pérez, E; Sarria Octavio de Toledo, L

    1994-10-01

    Two cases of prostate cancer (PC) which presented clinically with affectation of the cranial pairs due to skull base metastasis. In both cases, existence of intraparenchimatous brain metastasis was excluded. Initial improvement with hormonal therapy was followed by clinical, analytical and radiological relapse due to spread of process until death, at 11 and 36 months from diagnosis. Although PC's bone metastasis are frequent, their location at the skull base is uncommon. Even more rare are the cases which present with changes in the cranial pairs in the absence of signs and symptoms of prostatism.

  2. Development and external multicenter validation of Chinese Prostate Cancer Consortium prostate cancer risk calculator for initial prostate biopsy.

    Science.gov (United States)

    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

  3. Chemoprevention of prostate cancer: Natural compounds, antiandrogens, and antioxidants - In vivo evidence

    Directory of Open Access Journals (Sweden)

    Nur Özten-Kandas

    2011-01-01

    Full Text Available Prostate cancer is the leading non-skin malignancy detected in US males and the second cause of death due to male cancer, in the US. Interventions with drugs or diet supplements that slow down the growth and progression of prostate cancer are potentially very effective in reducing the burden of prostate cancer, particularly if these treatments also prevent the de novo development of new prostatic malignancies. Challenges to identify efficacious agents and develop them for chemopreventive application in men at risk for prostate cancer have included uncertainty about which preclinical models have the ability to predict efficacy in men and lack of consensus about which early phase clinical trial designs are the most appropriate and cost-effective to test promising agents. Efficacy studies in animal models have identified several agents with potential chemopreventive activity against prostate cancer, but few of these findings have been translated into clinical trials. This article identifies some of the major issues associated with prostate cancer chemoprevention research and summarizes the most significant current results from animal efficacy studies and human clinical prevention trials. This summary focuses on: (1 Naturally occurring agents and compounds derived from such agents, including green tea and its constituents, silibinin and milk thistle, and genistein and soy, (2 chemoprevention drugs including agents interfering with androgen action, and (3 antioxidants such as selenium, vitamin E, and lycopene. The general lack of activity of antioxidants is discussed, followed by considerations about translation of preclinical chemoprevention efficacy data, focusing on dose, form, bioavailability, and timing of administration of the agent, as well as discussion of study design of clinical trials and the predictive ability of preclinical models.

  4. Prioritizing genes associated with prostate cancer development

    International Nuclear Information System (INIS)

    Gorlov, Ivan P; Logothetis, Christopher J; Sircar, Kanishka; Zhao, Hongya; Maity, Sankar N; Navone, Nora M; Gorlova, Olga Y; Troncoso, Patricia; Pettaway, Curtis A; Byun, Jin Young

    2010-01-01

    The genetic control of prostate cancer development is poorly understood. Large numbers of gene-expression datasets on different aspects of prostate tumorigenesis are available. We used these data to identify and prioritize candidate genes associated with the development of prostate cancer and bone metastases. Our working hypothesis was that combining meta-analyses on different but overlapping steps of prostate tumorigenesis will improve identification of genes associated with prostate cancer development. A Z score-based meta-analysis of gene-expression data was used to identify candidate genes associated with prostate cancer development. To put together different datasets, we conducted a meta-analysis on 3 levels that follow the natural history of prostate cancer development. For experimental verification of candidates, we used in silico validation as well as in-house gene-expression data. Genes with experimental evidence of an association with prostate cancer development were overrepresented among our top candidates. The meta-analysis also identified a considerable number of novel candidate genes with no published evidence of a role in prostate cancer development. Functional annotation identified cytoskeleton, cell adhesion, extracellular matrix, and cell motility as the top functions associated with prostate cancer development. We identified 10 genes--CDC2, CCNA2, IGF1, EGR1, SRF, CTGF, CCL2, CAV1, SMAD4, and AURKA--that form hubs of the interaction network and therefore are likely to be primary drivers of prostate cancer development. By using this large 3-level meta-analysis of the gene-expression data to identify candidate genes associated with prostate cancer development, we have generated a list of candidate genes that may be a useful resource for researchers studying the molecular mechanisms underlying prostate cancer development

  5. Prostate cancer in Denmark

    DEFF Research Database (Denmark)

    Brasso, K; Friis, S; Kjaer, S K

    1998-01-01

    To review the trends in prostate cancer (PC) incidence and mortality rates in Denmark during a 50-year period.......To review the trends in prostate cancer (PC) incidence and mortality rates in Denmark during a 50-year period....

  6. Betulinic acid selectively increases protein degradation and enhances prostate cancer-specific apoptosis: possible role for inhibition of deubiquitinase activity.

    Directory of Open Access Journals (Sweden)

    Teresita Reiner

    Full Text Available Inhibition of the ubiquitin-proteasome system (UPS of protein degradation is a valid anti-cancer strategy and has led to the approval of bortezomib for the treatment of multiple myeloma. However, the alternative approach of enhancing the degradation of oncoproteins that are frequently overexpressed in cancers is less developed. Betulinic acid (BA is a plant-derived small molecule that can increase apoptosis specifically in cancer but not in normal cells, making it an attractive anti-cancer agent. Our results in prostate cancer suggested that BA inhibited multiple deubiquitinases (DUBs, which resulted in the accumulation of poly-ubiquitinated proteins, decreased levels of oncoproteins, and increased apoptotic cell death. In normal fibroblasts, however, BA did not inhibit DUB activity nor increased total poly-ubiquitinated proteins, which was associated with a lack of effect on cell death. In the TRAMP transgenic mouse model of prostate cancer, treatment with BA (10 mg/kg inhibited primary tumors, increased apoptosis, decreased angiogenesis and proliferation, and lowered androgen receptor and cyclin D1 protein. BA treatment also inhibited DUB activity and increased ubiquitinated proteins in TRAMP prostate cancer but had no effect on apoptosis or ubiquitination in normal mouse tissues. Overall, our data suggests that BA-mediated inhibition of DUBs and induction of apoptotic cell death specifically in prostate cancer but not in normal cells and tissues may provide an effective non-toxic and clinically selective agent for chemotherapy.

  7. Chemotherapeutic prevention studies of prostate cancer

    DEFF Research Database (Denmark)

    Djavan, Bob; Zlotta, Alexandre; Schulman, Claude

    2004-01-01

    Despite advances in the detection and management of prostate cancer, this disease remains a major cause of morbidity and mortality in men. Increasing attention has focused on the role of chemoprevention for prostate cancer, ie the administration of agents that inhibit 1 or more steps in the natural...... history of prostate carcinogenesis. We review prostate cancer chemoprevention studies in Europe....

  8. Obesity, body composition, and prostate cancer

    Directory of Open Access Journals (Sweden)

    Fowke Jay H

    2012-01-01

    Full Text Available Abstract Background Established risk factors for prostate cancer have not translated to effective prevention or adjuvant care strategies. Several epidemiologic studies suggest greater body adiposity may be a modifiable risk factor for high-grade (Gleason 7, Gleason 8-10 prostate cancer and prostate cancer mortality. However, BMI only approximates body adiposity, and may be confounded by centralized fat deposition or lean body mass in older men. Our objective was to use bioelectric impedance analysis (BIA to measure body composition and determine the association between prostate cancer and total body fat mass (FM fat-free mass (FFM, and percent body fat (%BF, and which body composition measure mediated the association between BMI or waist circumference (WC with prostate cancer. Methods The study used a multi-centered recruitment protocol targeting men scheduled for prostate biopsy. Men without prostate cancer at biopsy served as controls (n = 1057. Prostate cancer cases were classified as having Gleason 6 (n = 402, Gleason 7 (n = 272, or Gleason 8-10 (n = 135 cancer. BIA and body size measures were ascertained by trained staff prior to diagnosis, and clinical and comorbidity status were determined by chart review. Analyses utilized multivariable linear and logistic regression. Results Body size and composition measures were not significantly associated with low-grade (Gleason 6 prostate cancer. In contrast, BMI, WC, FM, and FFM were associated with an increased risk of Gleason 7 and Gleason 8-10 prostate cancer. Furthermore, BMI and WC were no longer associated with Gleason 8-10 (ORBMI = 1.039 (1.000, 1.081, ORWC = 1.016 (0.999, 1.033, continuous scales with control for total body FFM (ORBMI = 0.998 (0.946, 1.052, ORWC = 0.995 (0.974, 1.017. Furthermore, increasing FFM remained significantly associated with Gleason 7 (ORFFM = 1.030 (1.008, 1.052 and Gleason 8-10 (ORFFM = 1.044 (1.014, 1.074 after controlling for FM. Conclusions Our results

  9. Prostatic MR imaging. Accuracy in differentiating cancer from other prostatic disorders

    Energy Technology Data Exchange (ETDEWEB)

    Ikonen, S.; Kivisaari, L.; Tervahartiala, P. [Helsinki Univ. Central Hospital (Finland). Dept of Radiology; Vehmas, T. [Finnish Inst. of Occupational Health, Helsinki (Finland); Taari, K.; Rannikko, S. [Helsinki Univ. Central Hospital (Finland). Dept of Urology

    2001-03-01

    Purpose: We assessed the accuracy of MR imaging in differentiating between cancer and other prostatic disorders, and evaluated the diagnostic criteria for various prostatic diseases. Material and Methods: A total of 74 endorectal coil MR studies were performed on 72 patients. Twenty patients had prostatic cancer, 20 benign prostatic hyperplasia (BPH), 4 acute bacterial prostatitis, 5 chronic bacterial prostatitis (2 also belonging to the previous category), 19 chronic non-bacterial prostatitis/chronic pelvic pain syndrome, and 6 were symptomless voluntary controls. All studies were interpreted by two experienced radiologists in random order. Radiologists were blinded to all clinical data including the age of the patients. Based on MR findings, both radiologists filled in a form covering diagnostic criteria and diagnosis. Results: Accuracy in diagnosing prostate cancer was 74%. Sensitivity was 50% and specificity 83%, and positive and negative predictive values were 53 and 82%, respectively. Bacterial prostatitis showed some features similar to carcinoma. Abundant BPH rendered cancer detection more difficult. No diagnostic criterion was clearly better than the others. Interobserver agreement on the MR diagnosis ranged from moderate to good. Conclusion: Without knowledge of accurate clinical data, MR seems to be too insensitive in detecting prostate cancer to be used as a primary diagnostic tool.

  10. Beyond Seed and Soil: Understanding and Targeting Metastatic Prostate Cancer; Report From the 2016 Coffey-Holden Prostate Cancer Academy Meeting.

    Science.gov (United States)

    Miyahira, Andrea K; Roychowdhury, Sameek; Goswami, Sangeeta; Ippolito, Joseph E; Priceman, Saul J; Pritchard, Colin C; Sfanos, Karen S; Subudhi, Sumit K; Simons, Jonathan W; Pienta, Kenneth J; Soule, Howard R

    2017-02-01

    The 2016 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Beyond Seed and Soil: Understanding and Targeting Metastatic Prostate Cancer," was held from June 23 to June 26, 2016, in Coronado, California. For the 4th year in a row, the Prostate Cancer Foundation (PCF) hosted the CHPCA Meeting, a think tank-structured scientific conference, which focuses on a specific topic of critical unmet need on the biology and treatment of advanced prostate cancer. The 2016 CHPCA Meeting was attended by 71 investigators from prostate cancer and other fields, who discussed the biology, study methodologies, treatment strategies, and critical unmet needs concerning metastatic prostate cancer, with the ultimate goal of advancing strategies to treat and eliminate this disease. The major topics of discussion included: the molecular landscape and molecular heterogeneity of metastatic prostate cancer, the role of the metastatic microenvironment, optimizing immunotherapy in metastatic prostate cancer, learning from exceptional responders and non-responders, targeting DNA repair deficiency in advanced prostate cancer, developing and applying novel biomarkers and imaging techniques, and potential roles for the microbiome in prostate cancer. This article reviews the topics presented and discussions held at the CHPCA Meeting, with a focus on the unknowns and next steps needed to advance our understanding of the biology and most effective treatment strategies for metastatic prostate cancer. Prostate 77:123-144, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Schiff base-Poloxamer P85 combination demonstrates chemotherapeutic effect on prostate cancer cells in vitro.

    Science.gov (United States)

    Demirci, Selami; Doğan, Ayşegül; Türkmen, Neşe Başak; Telci, Dilek; Rizvanov, Albert A; Şahin, Fikrettin

    2017-02-01

    Prostate cancer is a multistep and complicated cancer type that is regulated by androgens at the cellular level and remains the second commonest cause of death among men. Discovery and development of novel chemotherapeutic agents enabling rapid tumor cell death with minimal toxic effects to healthy tissues might greatly improve the safety of chemotherapy. The present study evaluates the anti-cancer activity of a novel heterodinuclear copper(II)Mn(II) complex (Schiff base) in combination with poly(ethylene oxide) and poly(propylene oxide) block copolymer (Pluronic) P85. We used assays for cell proliferation, apoptosis, cell migration and invasion, DNA binding and cleavage to elucidate the molecular mechanisms of action, in addition to the anti-inflammatory potency of the new combination. The combined treatment of Schiff base and P85 lead to a remarkable anti-cancer effect on prostate cancer cell lines. Cell proliferation was inhibited in Schiff base-P85 treatment. The activity of this formulation is on DNA binding and cleavage and prevents inflammation in in vitro conditions. This is the first study presenting the anti-cancer activity of the present Schiff base derivative and its combination with P85 to treat prostate cancer in vitro. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. PSA-selective activation of cytotoxic human serine proteases within the tumor microenvironment as a therapeutic strategy to target prostate cancer.

    Science.gov (United States)

    Rogers, Oliver C; Anthony, Lizamma; Rosen, D Marc; Brennen, W Nathaniel; Denmeade, Samuel R

    2018-04-27

    Prostate cancer is the most diagnosed malignancy and the second leading cause of cancer-related death in American men. While localized therapy is highly curative, treatments for metastatic prostate cancer are largely palliative. Thus, new innovative therapies are needed to target metastatic tumors. Prostate-Specific Antigen (PSA) is a chymotrypsin-like protease with a unique substrate specificity that is secreted by both normal and malignant prostate epithelial cells. Previous studies demonstrated the presence of high levels (μM-mM) of enzymatically active PSA is present in the extracellular fluid of the prostate cancer microenvironment. Because of this, PSA is an attractive target for a protease activated pro-toxin therapeutic strategy. Because prostate cancers typically grow very slowly, a strategy employing a proliferation-independent cytotoxic payload is preferred. Recently, it was shown that the human protease Granzyme B (GZMB), at low micromolar concentrations in the extracellular space, can cleave an array of extracellular matrix (ECM) proteins thus perturbing cell growth, signaling, motility, and integrity. It is also well established that other human proteases such as trypsin can induce similar effects. Because both enzymes require N-terminal proteolytic activation, we propose to convert these proteins into PSA-activated cytotoxins. In this study, we examine the enzymatic and cell targeting parameters of these PSA-activated cytotoxic serine proteases. These pro-enzymes were activated robustly by PSA and induced ECM damage that led to the death of prostate cancer cells in vitro thus supporting the potential use of this strategy as means to target metastatic prostate cancers.

  13. Use of bis phosphonates in prostate cancer

    International Nuclear Information System (INIS)

    Della Valle, A.

    2004-01-01

    Prostate cancer is the second leading cause of cancer death in men in the world, meaning a real public health problem. The prevalence of Bone metastases may reach 100% of those who die from this disease printing a serious decline in the quality of life especially in the occurrence of skeletal-related events. Since three decades we try to find an inhibitor bone resorption which might prevent or treat bone metastases develop bisphosphonates (BF). These can not only inhibit the recruitment and differentiation osteoclast but decrease its half-life leading to early apoptosis. All BF have similar physicochemical properties and pharmacokinetics, but they differ in their anti-resorptive potency, ibandronate and zoledronic acid are BF generation that have been successful in the treatment of pain and decreased bone events in several works, however only one study randomized was conducted to show significant therapeutic advantages bone metastasis of prostate cancer. Although most authors indicate a therapeutic benefit, the evidence is weak and higher costs. Urges the implementation of new studies assessing both ibandronate and zoledronic acid in order to assert its virtues

  14. Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Mariela Rivera

    Full Text Available Curcumin, an extract from the turmeric rhizome (Curcuma longa, is known to exhibit anti-inflammatory, antioxidant, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Accumulative data indicate that curcumin may induce cancer cell death. However, the detailed mechanism underlying its pro-apoptotic and anti-cancer effects remains to be elucidated. In the present study, we examined the signaling pathways triggered by curcumin, specifically, the exact molecular mechanisms of curcumin-induced apoptosis in highly metastatic human prostate cancer cells. The effect of curcumin was evaluated using for the first time in prostate cancer, a gel-free shotgun quantitative proteomic analysis coupled with Tandem Mass Tag isobaric labeling-based-signaling networks. Results were confirmed at the gene expression level by qRT-PCR and at the protein expression level by western blot and flow cytometry. Our findings revealed that curcumin induced an Endoplasmic Reticulum stress-mediated apoptosis in PC3. The mechanisms by which curcumin promoted cell death in these cells were associated with cell cycle arrest, increased reactive oxygen species, autophagy and the Unfolded Protein Response. Furthermore, the upregulation of ER stress was measured using key indicators of ER stress: Glucose-Regulated Protein 78, Inositol-Requiring Enzyme 1 alpha, Protein Disulfide isomerase and Calreticulin. Chronic ER stress induction was concomitant with the upregulation of pro-apoptotic markers (caspases 3,9,12 and Poly (ADP-ribose polymerase. The downregulated proteins include anti-apoptotic and anti-tumor markers, supporting their curcumin-induced pro-apoptotic role in prostate cancer cells. Taken together, these data suggest that curcumin may serve as a promising anticancer agent by inducing a chronic ER stress mediated cell death and activation of cell cycle arrest, UPR, autophagy and oxidative stress responses.

  15. Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells

    Science.gov (United States)

    Rivera, Mariela; Ramos, Yanilda; Rodríguez-Valentín, Madeline; López-Acevedo, Sheila; Cubano, Luis A.; Zou, Jin; Zhang, Qiang; Wang, Guangdi

    2017-01-01

    Curcumin, an extract from the turmeric rhizome (Curcuma longa), is known to exhibit anti-inflammatory, antioxidant, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Accumulative data indicate that curcumin may induce cancer cell death. However, the detailed mechanism underlying its pro-apoptotic and anti-cancer effects remains to be elucidated. In the present study, we examined the signaling pathways triggered by curcumin, specifically, the exact molecular mechanisms of curcumin-induced apoptosis in highly metastatic human prostate cancer cells. The effect of curcumin was evaluated using for the first time in prostate cancer, a gel-free shotgun quantitative proteomic analysis coupled with Tandem Mass Tag isobaric labeling-based-signaling networks. Results were confirmed at the gene expression level by qRT-PCR and at the protein expression level by western blot and flow cytometry. Our findings revealed that curcumin induced an Endoplasmic Reticulum stress-mediated apoptosis in PC3. The mechanisms by which curcumin promoted cell death in these cells were associated with cell cycle arrest, increased reactive oxygen species, autophagy and the Unfolded Protein Response. Furthermore, the upregulation of ER stress was measured using key indicators of ER stress: Glucose-Regulated Protein 78, Inositol-Requiring Enzyme 1 alpha, Protein Disulfide isomerase and Calreticulin. Chronic ER stress induction was concomitant with the upregulation of pro-apoptotic markers (caspases 3,9,12) and Poly (ADP-ribose) polymerase. The downregulated proteins include anti-apoptotic and anti-tumor markers, supporting their curcumin-induced pro-apoptotic role in prostate cancer cells. Taken together, these data suggest that curcumin may serve as a promising anticancer agent by inducing a chronic ER stress mediated cell death and activation of cell cycle arrest, UPR, autophagy and oxidative stress responses. PMID:28628644

  16. β-catenin as a prognostic factor for prostate cancer (PCa)

    Science.gov (United States)

    Nowicki, Andrzej; Duda-Szymańska, Joanna

    2012-01-01

    Introduction The prostate cancer is difficult to predict, and treatment failure is associated with local infiltration, as well as distant metastases. Adhesion and migration abilities to of cancer cells play a major role in formation of metastasis. The participation of β-catenin in pathogene-sis of many types of cancer and benign processes has been an important discovery of recent years. Material and methods The studied material was obtained by transrectal, sextant core biopsy from 102 patients hospitalized in Department of Urology, Regional Hospital in Kalisz (2001-2004). The aim of our study was to determine the predictive value of β-catenin immunoexpression in prostate cancer, to analyze the prognostic aspect of some histopathological features and finally to assess the relationship between β-catenin immunoreactivity and the microscopic image of the tumor. Relationships between the investigated variables were analyzed using the Chi2 test of compatibility. We used the Kaplan-Meier curves to assess survival differences between groups of patients. Finally we established which of the studied factors significantly affect the patient outcome, using the method of Cox proportional hazard regression. Results In prostate cancer in comparison with the normal epithelium, both the location and the strength of β-catenin immunoexpression are impaired. Conclusions Our results indicate that the presence of disorders in β-catenin immunoexpression in prostate cancer cells indicates a high risk of death due to tumor progression and makes it imperative for immediate treatment procedures. PMID:24578946

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

    Science.gov (United States)

    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

  18. NCCU/BBRI-Duke/Urology Partnership In Prostate Cancer Research

    Science.gov (United States)

    2011-06-01

    UNC-CH Bowles Center for Alcohol Studies (“Mechanisms of alcohol pathology”, NIH/NIAAA U54AA019765). 2. “Pig Model of Gastroesophageal Reflux ...lines have also been adapted to the principal investigators laboratories for in vitro studies . Our collaboration has also led to the submission of...cause of cancer death in men. While one man in six will get prostate cancer during his lifetime, only one man in 35 will die of this disease

  19. SU-E-J-95: Predicting Treatment Outcomes for Prostate Cancer: Irradiation Responses of Prostate Cancer Stem Cells

    International Nuclear Information System (INIS)

    Wang, K

    2014-01-01

    Purpose: Most prostate cancers are slow-growing diseases but normally require much higher doses (80Gy) with conventional fractionation radiotherapy, comparing to other more aggressive cancers. This study is to disclose the radiobiological basis of this discrepancy by proposing the concept of prostate cancer stem cells (CSCs) and examining their specific irradiation responses. Methods: There are overwhelming evidences that CSC may keep their stemness, e.g. the competency of cell differentiation, in hypoxic microenvironments and hence become radiation resistive, though the probability is tiny for aggressiveness cancers. Tumor hypoxia used to be considered as an independent reason for poor treatment outcomes, and recent evidences showed that even prostate cancers were also hypoxic though they are very slow-growing. In addition, to achieve comparable outcomes to other much more aggressive cancers, much higher doses (rather than lower doses) are always needed for prostate cancers, regardless of its non-aggressiveness. All these abnormal facts can only be possibly interpreted by the irradiation responses characteristics of prostate CSCs. Results: Both normal cancer cells (NCCs) and CSCs exiting in tumors, in which NCCs are mainly for symptoms whereas killing all CSCs achieves disease-free. Since prostate cancers are slow-growing, the hypoxia in prostate cancers cannot possibly from NCCs, thus it is caused by hypoxic CSCs. However, single hypoxic cell cannot be imaged due to limitation of imaging techniques, unless a large group of hypoxic cells exist together, thus most of CSCs in prostate cancers are virtually hypoxic, i.e. not in working mode because CSCs in proliferating mode have to be normoxic, and this explains why prostate cancers are unaggressive. Conclusion: The fractional dose in conventional radiotherapy (∼2Gy) could only kill NCCs and CSCs in proliferating modes, whereas most CSCs survived fractional treatments since they were hypoxic, thus to eliminate all

  20. Prostate Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... HPV-Associated Lung Ovarian Skin Uterine Cancer Home Prostate Cancer Rates by Race and Ethnicity Language: English (US) ... Tweet Share Compartir The rate of men getting prostate cancer or dying from prostate cancer varies by race ...

  1. Prostate carcinoma: results of radiation therapy in the French Cancer Centres

    International Nuclear Information System (INIS)

    Allain, Y.M.; Bolla, M.; Douchez, J.; Gary-Bobo, J.; Geslin, J.; Huart, J.; Mazeron, J.J.; Mathieu, G.

    1985-01-01

    From 1975 to 1982, 597 patients with localized prostatic adenocarcinoma were treated using external beam irradiation in one of 6 cooperating centers. The mean patient age was 67 years. The 5 and 10 years actuarial survivals (including all causes of death) were 70% and 40% respectively. The adjusted survival rates become 86% at 5 years and 61% at 10 years when only death due to cancer is taken into consideration. Despite the fact that patients with stage A1 and A2 disease show different patterns of lymphatic spread, the actuarial and adjusted 8 years survivals were identical for both staging groups, in this study, 57% and 90% respectively. It is significant that the majority of patients in both group A1 and in group A2 received irradiation to the pelvic lymph nodes as well as the prostate. Patients with stage B1 disease showed a 7 years actuarial survival of 53% and an 82% survival adjusted for death due to cancer only. Patients in both group B2 and group C, showed an identical 10 year actuarial survival rate of 49%. However, without CT scanning, it is difficult to differentiate between these 2 staging groups. Patients with stage C2 disease showed 10 years actuarial and adjusted survival rates of 20% and 40% respectively. The local recurrence rate after primary radiation therapy did not exceed 11% in any patient group. These data demonstrate, once again, that the dogma pertaining to the radioresistance of prostatic cancer is outdated [fr

  2. Prostate cancer outcome in Burkina Faso

    Directory of Open Access Journals (Sweden)

    Yameogo Clotaire

    2011-09-01

    Full Text Available Abstract Introduction African-American black men race is one of non-modifiable risk factors confirmed for prostate cancer. Many studies have been done in USA among African- American population to evaluate prostate cancer disparities. Compared to the USA very few data are available for prostate cancer in Sub-Saharan African countries. The objective of this study was to describe incident prostate cancer (PC diagnosis characteristics in Burkina Faso (West Africa. Methods We performed a prospective non randomized patient’s cohort study of new prostate cancer cases diagnosed by histological analysis of transrectal prostate biopsies in Burkina Faso. Study participants included 166 patients recruited at the urology division of the university hospital of Ouagadougou. Age of the patients, clinical symptoms, digital rectal examination (DRE result, serum prostate-specific antigen (PSA level, histological characteristics and TNM classification were taking in account in this study. Results 166 transrectal prostate biopsies (TRPB were performed based on high PSA level or abnormal DRE. The prostate cancer rate on those TRPB was 63, 8 % (n=106. The mean age of the patients was 71, 5 years (52 to 86. Urinary retention was the first clinical patterns of reference in our institution (55, 7 %, n = 59. Most patients, 56, 6 % (n = 60 had a serum PSA level over than 100 ng/ml. All the patients had adenocarcinoma on histological study of prostate biopsy cores. The majority of cases (54, 7 % n = 58 had Gleason score equal or higher than 7. Conclusion Prostate cancer is diagnosed at later stages in our country. Very high serum PSA level and poorly differentiated tumors are the two major characteristics of PC at the time of diagnosis.

  3. Prevalence of benign prostatic hyperplasia and prostate cancer and its relative factors in Lanzhou

    International Nuclear Information System (INIS)

    Zhong Ganping; Wang Jiaji; Yue Zhongjin; Chen Xuehong

    2003-01-01

    To investigate the benign prostatic hyperplasia (BPH) and prostate cancer in Lanzhou, an investigation of the incidence of BPH and prostate cancer in 1356 male inhabitants over 50 years of age has been carried out including I-PSS, life quality (L), volume of prostate (V) and digital rectal examination. Plasma testosterone (T) and prostate specific antigen (PSA) were assayed in 145 cases. The incidence of BPH was 35.03%, being 41.04% in urban and 30.05% in rural inhabitants. The increase of BPH has been higher in urban inhabitants (P<0.05). The incidence of prostate cancer was 2.05%, being 3.09% in urban and 2.02% in rural inhabitants, the increase of prostate cancer has been higher in urban inhabitants (P< 0.05). A significant increase of prostate specific antigen was noted in prostate cancer patients (P<0.05). Conclusions: The increase of BPH and prostate cancer has been higher in urban inhabitants. The age, diet and residential areas might associate with a higher incidence of BPH and prostate cancer

  4. Tea, coffee and prostate cancer.

    Science.gov (United States)

    Lee, Andy H; Fraser, Michelle L; Binns, Colin W

    2009-02-01

    Worldwide, prostate cancer has the second highest incidence of all cancers in males with incidence and mortality being much higher in affluent developed countries. Risk and progression of the disease may be linked to both genetic and environmental factors, especially dietary factors. Tea and coffee are two of the most popular beverages in the world and have been investigated for possible effects on health outcomes, including cancer. However, very little dietary advice for their consumption exists. The evidence for a relationship between coffee or tea consumption and prostate cancer is reviewed in this paper. While current evidence indicates that coffee is a safe beverage, its consumption probably has no relationship with prostate cancer. Tea, especially green tea, has shown some potential in the prevention of prostate cancer. While evidence from epidemiologic studies is currently inconclusive, strong evidence has emerged from animal and in vitro studies. We also consider what level of evidence is required to make recommendations for preventive measures to the public. Although evidence on the relationship between coffee, tea and prostate cancer is not complete, we consider it strong enough to recommend tea as a healthier alternative to coffee.

  5. Does Small Prostate Predict High Grade Prostate Cancer?

    International Nuclear Information System (INIS)

    Caliskan, S.; Kaba, S.; Koca, O.; Ozturk, M. I.

    2017-01-01

    Objective: The current study is aimed to assess the patients who underwent radical prostatectomy for prostate cancer and investigate the association between prostate size and adverse outcomes at final pathology. Study Design: Comparative, descriptive study. Place and Duration of Study: Haydarpasa Numune Training and Research Hospital, Turkey, from January 2008 to January 2016. Methodology: The patients treated with open radical prostatectomy for prostate cancer were reviewed. Patient characteristics including prostate specific antigen (PSA), free PSA levels, age, biopsy, and radical prostatectomy results were recorded. The patients whose data were complete or prostate weight was equal to or less than 80 gm, were included in the study. Patients with < 40 gm prostate weight was in group 1 and the patients in group 2 had a prostate weight from 40 to 80 gm. High grade prostate cancer was defined to have a Gleason score between 7 or higher at biopsy and final pathology. Pathology and biopsy results were compared within groups. MedCalc Statistical Software demo version was used for statistical analyses. Results: There were 162 patients in this study. Of these, 71 (43.82 percent) patients were in group 1 and 91 (56.17 percent) patients were in group 2. The age ranged from 49 to 76 years. Mean value of 62.70 +-6.82 and 65.82 +- 5.66 years in group 1 and 2, respectively. Fifty (70.42 percent) and 68 patients (74.74 percent) had a Gleason score of 6 in group 1 and 2, respectively. Organconfined disease was reported in 53 patients (74.64 percent) in group 1 and in 78 patients (85.71 percent) in group 2. Gleason score concordance between biopsy and prostatectomy was reported in 61 patients (67.03 percent) and downgrading was detected in 4 patients (4.4 percent) in group 2. The median tumor volume of the patients was 4.47 cm/sup 3/ in group 1 and 6 cm/sup 3/ in group 2 (p=0.502). High grade prostate cancer was reported in 52.11 percent and 45.05 percent of the patients in

  6. Development of New Treatments for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    DiPaola, R. S.; Abate-Shen, C.; Hait, W. N.

    2005-02-01

    The Dean and Betty Gallo Prostate Cancer Center (GPCC) was established with the goal of eradicating prostate cancer and improving the lives of men at risk for the disease through research, treatment, education and prevention. GPCC was founded in the memory of Dean Gallo, a beloved New Jersey Congressman who died tragically of prostate cancer diagnosed at an advanced stage. GPCC unites a team of outstanding researchers and clinicians who are committed to high-quality basic research, translation of innovative research to the clinic, exceptional patient care, and improving public education and awareness of prostate cancer. GPCC is a center of excellence of The Cancer Institute of New Jersey, which is the only NCI-designated comprehensive cancer center in the state. GPCC efforts are now integrated well as part of our Prostate Program at CINJ, in which Dr. Robert DiPaola and Dr. Cory Abate-Shen are co-leaders. The Prostate Program unites 19 investigators from 10 academic departments who have broad and complementary expertise in prostate cancer research. The overall goal and unifying theme is to elucidate basic mechanisms of prostate growth and oncogenesis, with the ultimate goal of promoting new and effective strategies for the eradication of prostate cancer. Members' wide range of research interests collectively optimize the chances of providing new insights into normal prostate biology and unraveling the molecular pathophysiology of prostate cancer. Cell culture and powerful animal models developed by program members recapitulate the various stages of prostate cancer progression, including prostatic intraepithelial neoplasia, adenocarcinoma, androgen-independence, invasion and metastases. These models promise to further strengthen an already robust program of investigator-initiated therapeutic clinical trials, including studies adopted by national cooperative groups. Efforts to translate laboratory results into clinical studies of early detection and

  7. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer.

    Science.gov (United States)

    Fizazi, Karim; Tran, NamPhuong; Fein, Luis; Matsubara, Nobuaki; Rodriguez-Antolin, Alfredo; Alekseev, Boris Y; Özgüroğlu, Mustafa; Ye, Dingwei; Feyerabend, Susan; Protheroe, Andrew; De Porre, Peter; Kheoh, Thian; Park, Youn C; Todd, Mary B; Chi, Kim N

    2017-07-27

    Abiraterone acetate, a drug that blocks endogenous androgen synthesis, plus prednisone is indicated for metastatic castration-resistant prostate cancer. We evaluated the clinical benefit of abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer. In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 1199 patients to receive either androgen-deprivation therapy plus abiraterone acetate (1000 mg daily, given once daily as four 250-mg tablets) plus prednisone (5 mg daily) (the abiraterone group) or androgen-deprivation therapy plus dual placebos (the placebo group). The two primary end points were overall survival and radiographic progression-free survival. After a median follow-up of 30.4 months at a planned interim analysis (after 406 patients had died), the median overall survival was significantly longer in the abiraterone group than in the placebo group (not reached vs. 34.7 months) (hazard ratio for death, 0.62; 95% confidence interval [CI], 0.51 to 0.76; P<0.001). The median length of radiographic progression-free survival was 33.0 months in the abiraterone group and 14.8 months in the placebo group (hazard ratio for disease progression or death, 0.47; 95% CI, 0.39 to 0.55; P<0.001). Significantly better outcomes in all secondary end points were observed in the abiraterone group, including the time until pain progression, next subsequent therapy for prostate cancer, initiation of chemotherapy, and prostate-specific antigen progression (P<0.001 for all comparisons), along with next symptomatic skeletal events (P=0.009). These findings led to the unanimous recommendation by the independent data and safety monitoring committee that the trial be unblinded and crossover be allowed for patients in the placebo group to receive abiraterone. Rates of grade 3 hypertension and hypokalemia were higher in the abiraterone group. The addition of abiraterone

  8. Mortality from all cancers and lung, colorectal, breast and prostate cancer by country of birth in England and Wales, 2001-2003.

    Science.gov (United States)

    Wild, S H; Fischbacher, C M; Brock, A; Griffiths, C; Bhopal, R

    2006-04-10

    Mortality from all cancers combined and major cancers among men and women aged 20 years and over was compared by country of birth with that of the whole of England and Wales as the reference group. Population data from the 2001 Census and mortality data for 2001-2003 were used to estimate standardised mortality ratios. Data on approximately 399 000 cancer deaths were available, with at least 400 cancer deaths in each of the smaller populations. Statistically significant differences from the reference group included: higher mortality from all cancers combined, lung and colorectal cancer among people born in Scotland and Ireland, lower mortality for all cancers combined, lung, breast and prostate cancer among people born in Bangladesh (except for lung cancer in men), India, Pakistan or China/Hong Kong, lower lung cancer mortality among people born in West Africa or the West Indies, higher breast cancer mortality among women born in West Africa and higher prostate cancer mortality among men born in West Africa or the West Indies. These data may be relevant to causal hypotheses and in relation to health care and cancer prevention.

  9. Neuroendocrine differentiation in prostate cancer – a review

    Directory of Open Access Journals (Sweden)

    R. Popescu

    2015-12-01

    Full Text Available Objectives: This review aims to provide practicing clinicians with the most recent knowledge of the biological nature of prostate cancer especially the information regarding neuroendocrine differentiation. Methods: Review of the literature using PubMed search and scientific journal publications. Results: Much progress has been made towards an understanding of the development and progression of prostate cancer. The prostate is a male accessory sex gland which produces a fraction of seminal fluid. The normal human prostate is composed of a stromal compartment (which contains: nerves, fibroblast, smooth muscle cells, macrophages surrounding glandular acins – epithelial cells. Neuroendocrine cells are one of the epithelial populations in the normal prostate and are believed to provide trophic signals trough the secretion of neuropeptides that diffuse and influence surrounding epithelial cells. Prostate cancer is the most frequently diagnosed malignancy in men. In prostate cancer, neuroendocrine cells can stimulate growth of surrounding prostate adenocarcinoma cells (proliferation of neighboring cancer cells in a paracrine manner by secretion of neuroendocrine products. Neuroendocrine prostate cancer is an aggressive variant of prostate cancer that commonly arises in later stages of castration resistant prostate cancer. The detection of neuroendocrine prostate cancer has clinical implications. These patients are often treated with platinum chemotherapy rather than with androgen receptor targeted therapies. Conclusion: This review shows the need to improve our knowledge regarding diagnostic and treatment methods of the Prostate Cancer, especially cancer cells with neuroendocrine phenotype.

  10. New Prostate Cancer Treatment Target

    Science.gov (United States)

    Researchers have identified a potential alternative approach to blocking a key molecular driver of an advanced form of prostate cancer, called androgen-independent or castration-resistant prostate cancer.

  11. Prostate-specific antigen density: correlation with histological diagnosis of prostate cancer, benign prostatic hyperplasia and prostatitis

    NARCIS (Netherlands)

    van Iersel, M. P.; Witjes, W. P.; de la Rosette, J. J.; Oosterhof, G. O.

    1995-01-01

    To assess the additional value of prostate-specific antigen density in the diagnosis of prostate cancer in patients who undergo prostate biopsies. The study comprised 376 patients with symptoms of prostatism who were undergoing prostate biopsy. Digital rectal examination (DRE) and transrectal

  12. Is Preoperative Neutrophil Lymphocyte Ratio a Reliable Prognostic Parameter for Localized Prostate Cancer?

    Directory of Open Access Journals (Sweden)

    Tümay İpekçi

    2017-12-01

    Full Text Available Objective: In spite of all efforts, prostate cancer is still the 2nd highest cause of cancer-related deaths in men. For this reason new developments are needed in diagnosis, treatment and follow-up of prostate cancer. Neutrophil/lymphocyte (N/L ratio is a cheap and effective parameter used for research into many solid tumors; but there are not enough studies on the reliability of this parameter in prostate cancer. In this study we researched the efficacy of N/L ratio in localized prostate cancer. Materials and Methods: Between March 9, 2012 and April 23, 2017, the data of 140 patients who underwent radical prostatectomy with localized prostate cancer were screened retrospectively. The patients’ ages, preoperative prostate specific antigen (PSA and N/L ratio, pathologic stage, pathologic Gleason score, tumor volume, lymph node involvement, surgical margin positivity and presence or absence of 3rd month biochemical recurrence were noted. The correlations between N/L ratio with age, PSA, pathologic parameters, surgical margin positivity and biochemical recurrence were investigated. Results: The mean age of patients was 63.0±5.9 years, mean PSA value was 10.8±8.5 ng/mL and mean N/L ratio was 2.5±1.9. There was no correlation found between N/L ratio and PSA, pathologic stage, Gleason score, lymph node involvement, tumor volume, surgical margin positivity and biochemical recurrence (p>0.05. Conclusion: In our study investigating 140 patients with localized prostate cancer, we did not identify any correlation between N/L ratio and PSA, surgical stage and Gleason score, surgical margin positivity, and 3rd month biochemical recurrence. When the literature is investigated, it appears that N/L ratio is effective for metastatic prostate cancer. To provide a more accurate judgment of the role of N/L ratio in localized prostate cancer, there is a need for new studies with broader patient series.

  13. Long and noncoding RNAs (lnc-RNAs determine androgen receptor dependent gene expression in prostate cancer growth in vivo

    Directory of Open Access Journals (Sweden)

    Richard G Pestell

    2014-04-01

    Full Text Available Hyperactive androgen receptor (AR activity remains a key determinant of the onset and progression of prostate cancer and resistance to current therapies. The mechanisms governing castrate resistant prostate cancer are poorly understood, but defining these molecular events is essential in order to impact deaths from prostate cancer. Yang et al. demonstrate that two lnc-RNAs known to be overexpressed in therapy resistant prostate cancer, PRNCR1 (also known as PCAT8 and PCGEM1, bound to the AR to enhance ligand-dependent and ligand-independent AR gene expression and proliferation of prostate cancer cells.1 The sequence of these interactions involved the binding of PRNCR1 to the acetylated AR and a subsequent association of DOT1L, which was required for the sequential recruitment of the lncRNA PCGEM1 to the AR amino terminus, which in turn was methylated by DOT1L.

  14. Prostate cancer and social media.

    Science.gov (United States)

    Loeb, Stacy; Katz, Matthew S; Langford, Aisha; Byrne, Nataliya; Ciprut, Shannon

    2018-04-11

    The use of social media is increasing globally and is employed in a variety of ways in the prostate cancer community. In addition to their use in research, advocacy, and awareness campaigns, social media offer vast opportunities for education and networking for patients with prostate cancer and health-care professionals, and many educational resources and support networks are available to patients with prostate cancer and their caregivers. Despite the considerable potential for social media to be employed in the field of prostate cancer, concerns remain - particularly regarding the maintenance of patient confidentiality, variable information quality, and possible financial conflicts of interest. A number of professional societies have, therefore, issued guidance regarding social media use in medicine. Social media are used extensively in other cancer communities, particularly among patients with breast cancer, and both the quantity and type of information available are expected to grow in the future.

  15. Up-regulated microRNA-143 in cancer stem cells differentiation promotes prostate cancer cells metastasis by modulating FNDC3B expression

    International Nuclear Information System (INIS)

    Fan, Xinlan; Chen, Xu; Deng, Weixi; Zhong, Guangzheng; Cai, Qingqing; Lin, Tianxin

    2013-01-01

    Metastatic prostate cancer is a leading cause of cancer-related death in men. Cancer stem cells (CSCs) are involved in tumor progression and metastasis, including in prostate cancer. There is an obvious and urgent need for effective cancer stem cells specific therapies in metastatic prostate cancer. MicroRNAs (miRNAs) are an important class of pervasive genes that are involved in a variety of biological functions, especially in cancer. The goal of this study was to identify miRNAs involved in prostate cancer metastasis and cancer stem cells. A microarray and qRT-PCR were performed to investigate the miRNA expression profiles in PC-3 sphere cells and adherent cells. A transwell assay was used to evaluate the migration of PC-3 sphere cells and adherent cells. MiR-143 was silenced with antisense oligonucleotides in PC-3, PC-3-M and LNCaP cells. The role of miR-143 in prostate cancer metastasis was measured by wound-healing and transwell assays in vitro and bioluminescence imaging in vivo. Bioinformatics and luciferase report assays were used to identify the target of miR-143. The expression of miR-143 and the migration capability were reduced in PC-3 sphere cells and progressively increased during sphere re-adherent culture. Moreover, the down-regulation of miR-143 suppressed prostate cancer cells migration and invasion in vitro and systemically inhibited metastasis in vivo. Fibronectin type III domain containing 3B (FNDC3B), which regulates cell motility, was identified as a target of miR-143. The inhibition of miR-143 increased the expression of FNDC3B protein but not FNDC3B mRNA in vitro and vivo. These data demonstrate for the first time that miR-143 was up-regulated during the differentiation of prostate cancer stem cells and promoted prostate cancer metastasis by repressing FNDC3B expression. This sheds a new insight into the post-transcriptional regulation of cancer stem cells differentiation by miRNAs, a potential approach for the treatment of prostate cancer

  16. Inflammatory Genetic Markers of Prostate Cancer Risk

    International Nuclear Information System (INIS)

    Tindall, Elizabeth A.; Hayes, Vanessa M.; Petersen, Desiree C.

    2010-01-01

    Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk

  17. Inflammatory Genetic Markers of Prostate Cancer Risk

    Energy Technology Data Exchange (ETDEWEB)

    Tindall, Elizabeth A.; Hayes, Vanessa M. [Cancer Genetics Group, Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, PO Box 81, Randwick, NSW 2031 (Australia); University of New South Wales, Kensington Campus, Sydney, NSW 2052 (Australia); Petersen, Desiree C., E-mail: dpetersen@ccia.unsw.edu.au [Cancer Genetics Group, Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, PO Box 81, Randwick, NSW 2031 (Australia)

    2010-06-08

    Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk.

  18. Localized field conformation radiotherapy combined with endocrine therapy for the treatment of prostate cancer

    International Nuclear Information System (INIS)

    Karasawa, Katsuyuki; Kaizu, Toshihide; Kurosaki, Hiromasa; Tanaka, Yoshiaki

    1999-01-01

    To improve the quality of life (QOL) of the patients with prostate cancer, we limit the radiotherapy target volume to the prostate and seminal vesicles while using endocrine therapy towards the disease outside the target volume. Radiotherapy technique was rotation conformation technique with computer-controlled multileaf collimators to the total doses of up to 66-70 Gy. Among 145 evaluable cases with the median age of 74, overall and cause-specific 5-year survival rates were 59.3% and 84.1%, respectively, and the relative survival rate of the Stage A-C cases was 100%. The two thirds (33/50) of the deaths were not of prostate cancer. The rate of severe complication was 1.4%. As for QOL, the rate of impotence was 90%, however, the patients' overall satisfaction towards the treatment was 90%. From this analysis, this combined treatment seems beneficial in the treatment of prostate cancer. (author)

  19. The relationship between Prostate CAncer gene 3 (PCA3) and prostate cancer significance

    NARCIS (Netherlands)

    van Poppel, Hein; Haese, Alexander; Graefen, Markus; de la Taille, Alexandre; Irani, Jacques; de Reijke, Theo; Remzi, Mesut; Marberger, Michael

    2012-01-01

    OBJECTIVE To evaluate the relationship between Prostate CAncer gene 3 (PCA3) and prostate cancer significance. PATIENTS AND METHODS Clinical data from two multi-centre European open-label, prospective studies evaluating the clinical utility of the PCA3 assay in guiding initial and repeat biopsy

  20. Vitamins, metabolomics, and prostate cancer.

    Science.gov (United States)

    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.

  1. Diagnostic utility of DTI in prostate cancer

    International Nuclear Information System (INIS)

    Guerses, Bengi; Tasdelen, Neslihan; Yencilek, Faruk; Kilickesmez, N. Ozguer; Alp, Turgut; Firat, Zeynep; Albayrak, M. Selami; Ulug, Aziz M.; Guermen, A. Nevzat

    2011-01-01

    Purpose: The aim of this study was to compare the diffusion tensor parameters of prostate cancer, prostatitis and normal prostate tissue. Materials and Methods: A total of 25 patients with the suspicion of prostate cancer were included in the study. MRI was performed with 3 T system (Intera Achieva, Philips Medical Systems, The Netherlands). T2 TSE and DTI with ss-EPI were obtained in each subject. TRUS-guided prostate biopsy was performed after the MRI examination. Images were analyzed by two radiologists using a special software system. ROI's were drawn according to biopsy zones which are apex, midgland, base and central zone on each sides of the gland. FA and ADC values in areas of cancer, chronic prostatitis and normal prostate tissue were compared using Student's t-test. Results: Histopathological analysis revealed carcinoma in 68, chronic prostatitis in 67 and was reported as normal in 65 zones. The mean FA of cancerous tissue was significantly higher (p < 0.01) than the FA of chronic prostatitis and normal gland. The mean ADC of cancerous tissue was found to be significantly lower (p < 0.01), compared with non-cancerous tissue. Conclusion: Decreased ADC and increased FA are compatible with the hypercellular nature of prostate tumors. These differences may increase the accuracy of MRI in the detection of carcinoma and to differentiate between cancer and prostatitis.

  2. Diagnostic utility of DTI in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Guerses, Bengi, E-mail: bengur0@yahoo.com [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey); Tasdelen, Neslihan [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey); Yencilek, Faruk [Yeditepe University Medical Faculty, Department of Urology, Istanbul (Turkey); Kilickesmez, N. Ozguer [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey); Alp, Turgut [Fatih Sultan Mehmet Training and Research Hospital, Division of Urology, Istanbul (Turkey); Firat, Zeynep [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey); Albayrak, M. Selami [Kartal Training and Research Hospital, Division of Urology, Istanbul (Turkey); Ulug, Aziz M. [Yeditepe University Department of Biomedical Engineering, Istanbul (Turkey); The Feinstein Institute for Medical Research, Manhasset, New York (United States); Guermen, A. Nevzat [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey)

    2011-08-15

    Purpose: The aim of this study was to compare the diffusion tensor parameters of prostate cancer, prostatitis and normal prostate tissue. Materials and Methods: A total of 25 patients with the suspicion of prostate cancer were included in the study. MRI was performed with 3 T system (Intera Achieva, Philips Medical Systems, The Netherlands). T2 TSE and DTI with ss-EPI were obtained in each subject. TRUS-guided prostate biopsy was performed after the MRI examination. Images were analyzed by two radiologists using a special software system. ROI's were drawn according to biopsy zones which are apex, midgland, base and central zone on each sides of the gland. FA and ADC values in areas of cancer, chronic prostatitis and normal prostate tissue were compared using Student's t-test. Results: Histopathological analysis revealed carcinoma in 68, chronic prostatitis in 67 and was reported as normal in 65 zones. The mean FA of cancerous tissue was significantly higher (p < 0.01) than the FA of chronic prostatitis and normal gland. The mean ADC of cancerous tissue was found to be significantly lower (p < 0.01), compared with non-cancerous tissue. Conclusion: Decreased ADC and increased FA are compatible with the hypercellular nature of prostate tumors. These differences may increase the accuracy of MRI in the detection of carcinoma and to differentiate between cancer and prostatitis.

  3. Psychosocial Consequences of Overdiagnostic of Prostate Cancer

    DEFF Research Database (Denmark)

    Nielsen, Sigrid Brisson

    Psychosocial Consequences of Overdiagnostic of Prostate Cancer Sigrid Brisson Nielsen & John Brodersen Introduction In Denmark there are approximately 4400 men diagnosed with prostate cancer each year and nearly 1200 men dies of this disease yearly. The incidence of prostate cancer has increased...... for the past twenty years and make up 24 % of all cancer incidents in men. However, the mortality of prostate cancer has not changed in line with this increase. Empirical evidence shows that the increase in incidence of prostate cancer in Denmark without an increase in the mortality is mostly caused...... by opportunistic PSA screening in General Practice. It is recommended that men ≥ 60 year old diagnosed with prostate cancer and a Gleason score ≤ 6 are monitored with active surveillance. This is due to the probability of this type of cancer metastasizing is very small as approximately 90 % of them is assumed...

  4. Cancer of the prostate - role of PSA

    International Nuclear Information System (INIS)

    Shittu, O.B.

    1999-02-01

    Since 1979 when prostate specific antigen (PSA), found in the cytoplasm of benign and malignant prostatic cells, was first purified, it has attained world wide popularity in prostate cancer detection. It is also a sensitive test for skeletal meta states from carcinoma of the prostate. Prostate cancer has become the number one cancer in men and constitutes 11% of all cancers. Approximately 50% of men over 50 years have symptoms referable to the lower urinary tract. 50% or more of patients at Ibadan present an advanced stage of the disease and are therefore not curable. Thus, lacking the skill to manage advanced manifestations, early detection and screening programs are the best means to reduce mortality due to prostate cancer

  5. Roswell Park Cancer Institute/Howard University Prostate Cancer Scholars Program

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-14-1-0531 TITLE: Roswell Park Cancer Institute/Howard University Prostate Cancer Scholars Program PRINCIPAL INVESTIGATOR...Roswell Park Cancer Institute/Howard University Prostate Cancer 5a. CONTRACT NUMBER W81XWH-14-1-0531 Cancer Scholars Program 5b. GRANT NUMBER 5c...Prostate Cancer Scholars Program is designed to encourage students from under-represented minority groups to enter graduate training and ultimately

  6. A novel minimally invasive dual-modality fiber optic probe for prostate cancer detection

    Science.gov (United States)

    Sharma, Vikrant

    Prostate cancer is the most common form of cancer in males, and is the second leading cause of cancer related deaths in United States. In prostate cancer diagnostics and therapy, there is a critical need for a minimally invasive tool for in vivo evaluation of prostate tissue. Such a tool finds its niche in improving TRUS (trans-rectal ultrasound) guided biopsy procedure, surgical margin assessment during radical prostatectomy, and active surveillance of patients with a certain risk levels. This work is focused on development of a fiber-based dual-modality optical device (dMOD), to differentiate prostate cancer from benign tissue, in vivo. dMOD utilizes two independent optical techniques, LRS (light reflectance spectroscopy) and AFLS (auto-fluorescence lifetime spectroscopy). LRS quantifies scattering coefficient of the tissue, as well as concentrations of major tissue chromophores like hemoglobin derivatives, β-carotene and melanin. AFLS was designed to target lifetime signatures of multiple endogenous fluorophores like flavins, porphyrins and lipo-pigments. Each of these methods was independently developed, and the two modalities were integrated using a thin (1-mm outer diameter) fiber-optic probe. Resulting dMOD probe was implemented and evaluated on animal models of prostate cancer, as well as on human prostate tissue. Application of dMOD to human breast cancer (invasive ductal carcinoma) identification was also evaluated. The results obtained reveal that both LRS and AFLS are excellent techniques to discriminate prostate cancer tissue from surrounding benign tissue in animal models. Each technique independently is capable of providing near absolute (100%) accuracy for cancer detection, indicating that either of them could be used independently without the need of implementing them together. Also, in case of human breast cancer, LRS and AFLS provided comparable accuracies to dMOD, LRS accuracy (96%) being the highest for the studied population. However, the

  7. Trichostatin A (TSA) sensitizes the human prostatic cancer cell line DU145 to death receptor ligands treatment.

    Science.gov (United States)

    Taghiyev, Agshin F; Guseva, Natalya V; Sturm, Mary T; Rokhlin, Oskar W; Cohen, Michael B

    2005-04-01

    The human prostatic carcinoma cell line DU145 has previously been found to be resistant to treatment with TNF-family ligands. However, TRAIL, TNF-alpha and anti-Fas antibodies (Ab) treatment in combination with the histone deacetylase inhibitor Trichostatin A (TSA) converted the phenotype of DU145 from resistant to sensitive. TSA induced 15% cell death but simultaneous treatment with TRAIL, TNF-alpha and anti-Fas Ab resulted in 55%, 70% and 40% cell death, respectively. Simultaneous treatment did not increase the level of TSA-induced histone acetylation, but induced the release of acetylated histones from chromatin into the cytosol. This release was caspase dependent since it was abrogated by Z-VAD-fmk. In addition, treatment with TSA induced caspase-9 activation and resulted in the release of cytochrome c and Smac/DIABLO from mitochondria. To further investigate the role of caspase-9 in TSA-mediated apoptosis we used two different approaches: (1) cells were pretreated with the caspase-9 inhibitor Z-LEHD-fmk, and (2) cells were transfected with a dominant-negative form of caspase-9. Both approaches gave similar results: cells became resistant to treatment with TSA. These data indicate that TSA mediates its effect via the mitochondrial pathway. This was confirmed by examining DU145 overexpressing Bcl-2. These transfectants were resistant to TSA treatment. Taken together, our data shows that only simultaneous treatment with TNF-family ligands and TSA in DU145 resulted in caspase activity sufficient to induce apoptosis. The combination of TSA and TNF-family ligands could potentially be the basis for the treatment of prostate cancer.

  8. Punctuated evolution of prostate cancer genomes.

    Science.gov (United States)

    Baca, Sylvan C; Prandi, Davide; Lawrence, Michael S; Mosquera, Juan Miguel; Romanel, Alessandro; Drier, Yotam; Park, Kyung; Kitabayashi, Naoki; MacDonald, Theresa Y; Ghandi, Mahmoud; Van Allen, Eliezer; Kryukov, Gregory V; Sboner, Andrea; Theurillat, Jean-Philippe; Soong, T David; Nickerson, Elizabeth; Auclair, Daniel; Tewari, Ashutosh; Beltran, Himisha; Onofrio, Robert C; Boysen, Gunther; Guiducci, Candace; Barbieri, Christopher E; Cibulskis, Kristian; Sivachenko, Andrey; Carter, Scott L; Saksena, Gordon; Voet, Douglas; Ramos, Alex H; Winckler, Wendy; Cipicchio, Michelle; Ardlie, Kristin; Kantoff, Philip W; Berger, Michael F; Gabriel, Stacey B; Golub, Todd R; Meyerson, Matthew; Lander, Eric S; Elemento, Olivier; Getz, Gad; Demichelis, Francesca; Rubin, Mark A; Garraway, Levi A

    2013-04-25

    The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term "chromoplexy," frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Pubertal development and prostate cancer risk

    DEFF Research Database (Denmark)

    Bonilla, Carolina; Lewis, Sarah J; Martin, Richard M

    2016-01-01

    , 0.91-1.00) and prostate cancer-specific mortality (hazard ratio amongst cases, per tertile: 0.94; 95 % CI, 0.90-0.98), but not with disease grade. CONCLUSIONS: Older age at sexual maturation is causally linked to a reduced risk of later prostate cancer, especially aggressive disease.......BACKGROUND: Epidemiological studies have observed a positive association between an earlier age at sexual development and prostate cancer, but markers of sexual maturation in boys are imprecise and observational estimates are likely to suffer from a degree of uncontrolled confounding. To obtain...... to a difference of one Tanner stage between pubertal boys of the same age) was associated with a 77 % (95 % CI, 43-91 %) reduced odds of high Gleason prostate cancer. In PRACTICAL, the puberty genetic score was associated with prostate cancer stage (OR of advanced vs. localized cancer, per tertile: 0.95; 95 % CI...

  10. Sleep disruption, chronotype, shift work, and prostate cancer risk and mortality: a 30-year prospective cohort study of Finnish twins.

    Science.gov (United States)

    Dickerman, Barbra A; Markt, Sarah C; Koskenvuo, Markku; Hublin, Christer; Pukkala, Eero; Mucci, Lorelei A; Kaprio, Jaakko

    2016-11-01

    Sleep disruption and shift work have been associated with cancer risk, but epidemiologic evidence for prostate cancer remains limited. We aimed to prospectively investigate the association between midlife sleep- and circadian-related parameters and later prostate cancer risk and mortality in a population-based cohort of Finnish twins. Data were drawn from the Older Finnish Twin Cohort and included 11,370 twins followed from 1981 to 2012. Over the study period, 602 incident cases of prostate cancer and 110 deaths from prostate cancer occurred. Cox regression was used to evaluate associations between midlife sleep duration, sleep quality, chronotype, and shift work with prostate cancer risk and prostate cancer-specific mortality. Within-pair co-twin analyses were employed to account for potential familial confounding. Compared to "definite morning" types, "somewhat evening" types had a significantly increased risk of prostate cancer (HR 1.3; 95 % CI 1.1, 1.6). Chronotype significantly modified the relationship between shift work and prostate cancer risk (p-interaction shift work and prostate cancer risk in the overall analyses and no significant association between any sleep- or circadian-related parameter and risk in co-twin analyses. Neither sleep- nor circadian-related parameters were significantly associated with prostate cancer-specific mortality. The association between sleep disruption, chronotype, and shift work with prostate cancer risk and mortality has never before been studied in a prospective study of male twins. Our findings suggest that chronotype may be associated with prostate cancer risk and modify the association between shift work and prostate cancer risk. Future studies of circadian disruption and prostate cancer should account for this individual-level characteristic.

  11. Mitochondrial mutations drive prostate cancer aggression

    DEFF Research Database (Denmark)

    Hopkins, Julia F.; Sabelnykova, Veronica Y.; Weischenfeldt, Joachim

    2017-01-01

    Nuclear mutations are well known to drive tumor incidence, aggression and response to therapy. By contrast, the frequency and roles of mutations in the maternally inherited mitochondrial genome are poorly understood. Here we sequence the mitochondrial genomes of 384 localized prostate cancer...... in prostate cancer, and suggest interplay between nuclear and mitochondrial mutational profiles in prostate cancer....

  12. Prostate-specific antigen: does the current evidence support its use in prostate cancer screening?

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

    Although widely used, the value of prostate-specific antigen (PSA) in screening asymptomatic men for prostate cancer is controversial. Reasons for the controversy relate to PSA being less than an ideal marker in detecting early prostate cancer, the possibility that screening for prostate cancer may result in the overdetection and thus overtreatment of indolent disease and the lack of clarity as to the definitive or best treatment for men diagnosed with localized prostate cancer. Although the results from some randomized prospective trials suggest that screening with PSA reduces mortality from prostate cancer, the overall benefit was modest. It is thus currently unclear as to whether the modest benefit of reduced mortality outweighs the harms of overdetection and overtreatment. Thus, prior to undergoing screening for prostate cancer, men should be informed of the risks and benefits of early detection. Newly emerging markers that may complement PSA in the early detection of prostate cancer include specific isoforms of PSA and PCA3.

  13. Hyaluronan Biosynthesis in Prostate Cancer

    National Research Council Canada - National Science Library

    McCarthy, James B

    2006-01-01

    Despite advances in the diagnosis and treatment of prostate cancer in the last several years metastasis represents the major cause of frustration and failure in the successful treatment of prostate cancer patients. Hyaluronan (HA...

  14. Redox-Mediated and Ionizing-Radiation-Induced Inflammatory Mediators in Prostate Cancer Development and Treatment

    Science.gov (United States)

    Miao, Lu; Holley, Aaron K.; Zhao, Yanming; St. Clair, William H.

    2014-01-01

    Abstract Significance: Radiation therapy is widely used for treatment of prostate cancer. Radiation can directly damage biologically important molecules; however, most effects of radiation-mediated cell killing are derived from the generated free radicals that alter cellular redox status. Multiple proinflammatory mediators can also influence redox status in irradiated cells and the surrounding microenvironment, thereby affecting prostate cancer progression and radiotherapy efficiency. Recent Advances: Ionizing radiation (IR)–generated oxidative stress can regulate and be regulated by the production of proinflammatory mediators. Depending on the type and stage of the prostate cancer cells, these proinflammatory mediators may lead to different biological consequences ranging from cell death to development of radioresistance. Critical Issues: Tumors are heterogeneous and dynamic communication occurs between stromal and prostate cancer cells, and complicated redox-regulated mechanisms exist in the tumor microenvironment. Thus, antioxidant and anti-inflammatory strategies should be carefully evaluated for each patient at different stages of the disease to maximize therapeutic benefits while minimizing unintended side effects. Future Directions: Compared with normal cells, tumor cells are usually under higher oxidative stress and secrete more proinflammatory mediators. Thus, redox status is often less adaptive in tumor cells than in their normal counterparts. This difference can be exploited in a search for new cancer therapeutics and treatment regimes that selectively activate cell death pathways in tumor cells with minimal unintended consequences in terms of chemo- and radio-resistance in tumor cells and toxicity in normal tissues. Antioxid. Redox Signal. 20, 1481–1500. PMID:24093432

  15. Advances in MRI diagnosis of prostate cancer

    International Nuclear Information System (INIS)

    Zhang Longmin; Liu Ailian

    2014-01-01

    Prostate cancer is the second most common cancer in the world, and the incidence of prostate cancer in China shows an upward trend. MRI has high soft tissue resolution and multi-dimensional imaging advantages, and it can better show the anatomy of the prostate and adjacent tissue structures. With the development of MR technique, it plays a more and more important role in prostate cancer diagnosis. This review starts from the imaging performance of routine MRI sequence of prostate cancer, and a variety of functional MRI applications in the diagnosis and differential diagnosis of prostate cancer are described in detail, such as MR perfusion-weighted imaging, MR spectroscopy, MR diffusion-weighted imaging, MR diffusion tensor imaging, intravoxel incoherent motion diffusion-weighted imaging, MR susceptibility-weighted imaging. Meanwhile this review introduces that functional MRI has more advantages and can provide more image information than routine MRI sequence. According to a series of semi-quantitative and quantitative data, functional MRI can further provide the blood perfusion of prostate cancer, water molecule diffusion and microcirculation state, metabolism and biochemical composition change information. (authors)

  16. PET/CT Imaging and Radioimmunotherapy of Prostate Cancer

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Tagawa, Scott T; Goldsmith, Stanley J

    2011-01-01

    disease (ideal for antigen access and antibody delivery). Furthermore, prostate cancer is also radiation sensitive. Prostate-specific membrane antigen is expressed by virtually all prostate cancers, and represents an attractive target for RIT. Antiprostate-specific membrane antigen RIT demonstrates......Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an important role in the clinical management of patients with prostate cancer. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis...... of anatomic, functional, and molecular imaging information. Positron emission tomography (PET)/computed tomography (CT) in oncology is emerging as an important imaging tool. The most common radiotracer for PET/CT in oncology, (18)F-fluorodeoxyglucose (FDG), is not very useful in the imaging of prostate cancer...

  17. Targeting Discoidin Domain Receptors in Prostate Cancer

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-15-1-0226 TITLE: Targeting Discoidin Domain Receptors in Prostate Cancer PRINCIPAL INVESTIGATOR: Dr. Rafael Fridman...AND SUBTITLE 5a. CONTRACT NUMBER Targeting Discoidin Domain Receptors in Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0226 5c. PROGRAM ELEMENT...response to collagen in prostate cancer. The project’s goal is to define the expression and therapeutic potential of DDRs in prostate cancer. During

  18. Multiparametric MR imaging in diagnosis of chronic prostatitis and its differentiation from prostate cancer

    Directory of Open Access Journals (Sweden)

    Vivek Kumar Sah

    2015-03-01

    Full Text Available Chronic prostatitis is a heterogeneous condition with high prevalence rate. Chronic prostatitis has overlap in clinical presentation with other prostate disorders and is one of the causes of high serum prostate specific antigen (PSA level. Chronic prostatitis, unlike acute prostatitis, is difficult to diagnose reliably and accurately on the clinical grounds alone. Not only this, it is also challenging to differentiate chronic prostatitis from prostate cancer with imaging modalities like TRUS and conventional MR Imaging, as the findings can mimic those of prostate cancer. Even biopsy doesn't play promising role in the diagnosis of chronic prostatitis as it has limited sensitivity and specificity. As a result of this, chronic prostatitis may be misdiagnosed as a malignant condition and end up in aggressive surgical management resulting in increased morbidity. This warrants the need of reliable diagnostic tool which has ability not only to diagnose it reliably but also to differentiate it from the prostate cancer. Recently, it is suggested that multiparametric MR Imaging of the prostate could improve the diagnostic accuracy of the prostate cancer. This review is based on the critically published literature and aims to provide an overview of multiparamateric MRI techniques in the diagnosis of chronic prostatitis and its differentiation from prostate cancer.

  19. Genomic rearrangements of PTEN in prostate cancer

    Directory of Open Access Journals (Sweden)

    Sopheap ePhin

    2013-09-01

    Full Text Available The phosphatase and tensin homolog gene on chromosome 10q23.3 (PTEN is a negative regulator of the PIK3/Akt survival pathway and is the most frequently deleted tumor suppressor gene in prostate cancer. Monoallelic loss of PTEN is present in up to 60% of localized prostate cancers and complete loss of PTEN in prostate cancer is linked to metastasis and androgen independent progression. Studies on the genomic status of PTEN in prostate cancer initially used a two-color fluorescence in-situ hybridization (FISH assay for PTEN copy number detection in formalin fixed paraffin embedded tissue preparations. More recently, a four-color FISH assay containing two additional control probes flanking the PTEN locus with a lower false-positive rate was reported. Combined with the detection of other critical genomic biomarkers for prostate cancer such as ERG, AR, and MYC, the evaluation of PTEN genomic status has proven to be invaluable for patient stratification and management. Although less frequent than allelic deletions, point mutations in the gene and epigenetic silencing are also known to contribute to loss of PTEN function, and ultimately to prostate cancer initiation. Overall, it is clear that PTEN is a powerful biomarker for prostate cancer. Used as a companion diagnostic for emerging therapeutic drugs, FISH analysis of PTEN is promisingly moving human prostate cancer closer to more effective cancer management and therapies.

  20. Vietnam military service history and prostate cancer

    Directory of Open Access Journals (Sweden)

    Fritschi Lin

    2006-03-01

    Full Text Available Abstract Background Three decades after US and Australian forces withdrew from Vietnam, there has been much public interest in the health consequences of service in Vietnam. One controversial question is whether the risk of prostate cancer amongst Vietnam veterans is increased. This paper examines relationships between military history, family history and risk of prostate cancer in a population-based case control study. Methods Cases were selected from the Cancer Registry of Western Australia as incident cases of histologically-confirmed prostate cancer, and controls were age-matched and selected from the Western Australian electoral roll. Study participants were asked to report any military service history and details about that service. Results Between January 2001 and September 2002, 606 cases and 471 controls aged between 40–75 years were recruited. An increased prostate cancer risk was observed in men reporting they were deployed in Vietnam although this was not statistically significant (OR = 2.12; 95% CI 0.88–5.06. An increased risk was also observed in men reporting prostate cancer in fathers (OR = 1.90; 95% CI 1.20–3.00 or brothers (OR = 2.05; 95% CI 1.20–3.50 diagnosed with prostate cancer. Conclusion These findings support a positive association between prostate cancer and military service history in the Vietnam war and a first degree relative family history of prostate cancer.

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

    Science.gov (United States)

    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 prostatitis. All others were nonsignificant (P prostate abnormalities, especially differentiating BPH from prostate cancer and prostatitis. © 2014 Blackwell Verlag GmbH.

  2. Prostate cancer may trigger paraneoplastic limbic encephalitis

    DEFF Research Database (Denmark)

    Jakobsen, Jakob Kristian; Zakharia, Elias Raja; Boysen, Anders Kindberg Fossø

    2013-01-01

    -Hu antibody test the patient was diagnosed with paraneoplastic limbic encephalitis related to prostate cancer. The patient died within 6 months. We review the literature on prostate cancer-related paraneoplastic limbic encephalitis. High-risk prostate cancer can trigger paraneoplastic limbic encephalitis...

  3. Downregulation of ZNF132 in prostate cancer is associated with aberrant promoter hypermethylation and poor prognosis

    DEFF Research Database (Denmark)

    Abildgaard, Mette Opstrup; Borre, Michael; Mørck Mortensen, Martin

    2012-01-01

    This study investigates the expression and biomarker potential of zinc finger protein 132 (ZNF132) in prostate cancer (PC) by transcriptional profiling and immunohistochemical analysis of tissue microarrays, including tumor specimens from 615 radical prostatectomy (RP) patients and 199...... conservatively treated patients. Primary clinical endpoints were time to PSA recurrence and cancer-specific death, respectively. Compared to normal prostate epithelial cells from men without PC, ZNF132 transcript levels were significantly reduced in PC cells from patients with localized PC and further...... immunoreactivity was significantly associated with high Gleason score and advanced T stage in both PC patient cohorts. By univariate analysis, no/weak ZNF132 staining was a significant adverse predictor of PSA recurrence after RP (p = 0.024) and cancer-specific death following conservative treatment (p = 0...

  4. Residual Prostate Cancer in Patients Treated With Endocrine Therapy With or Without Radical Radiotherapy: A Side Study of the SPCG-7 Randomized Trial

    International Nuclear Information System (INIS)

    Solberg, Arne; Haugen, Olav A.; Viset, Trond; Bergh, Anders; Tasdemir, Ilker; Ahlgren, Goeran; Widmark, Anders; Angelsen, Anders

    2011-01-01

    Purpose: The Scandinavian Prostate Cancer Group-7 randomized trial demonstrated a survival benefit of combined endocrine therapy and external-beam radiotherapy over endocrine therapy alone in patients with high-risk prostate cancer. In a subset of the study population, the incidence and clinical implications of residual prostate cancer in posttreatment prostate biopsy specimens was evaluated. Methods and Materials: Biopsy specimens were obtained from 120 of 875 men in the Scandinavian Prostate Cancer Group-7 study. Results: Biopsies were performed at median of 45 months follow-up. In 63 patients receiving endocrine treatment only and 57 patients receiving combined treatment, residual cancer was found in 66% (n = 41) and 22% (n = 12), respectively (p < 0.0001). The vast majority of residual tumors were poorly differentiated (Gleason score ≥8). Endocrine therapy alone was predictive of residual prostate cancer: odds ratio 7.49 (3.18-17.7), p < 0.0001. In patients with positive vs. negative biopsy the incidences of clinical events were as follows: biochemical recurrence 74% vs. 27% (p < 0.0001), local progression 26% vs. 4.7% (p = 0.002), distant recurrence 17% vs. 9.4% (p = 0.27), clinical recurrence 36% vs. 13% (p = 0.006), cancer-specific death 19% vs. 9.7% (p = 0.025). In multivariable analysis, biochemical recurrence was significantly associated with residual cancer: hazard ratio 2.69 (1.45-4.99), p = 0.002, and endocrine therapy alone hazard ratio 3.45 (1.80-6.62), p < 0.0001. Conclusions: Radiotherapy combined with hormones improved local tumor control in comparison with endocrine therapy alone. Residual prostate cancer was significantly associated with serum prostate-specific antigen recurrence, local tumor progression, clinical recurrence, and cancer-specific death in univariable analysis. Residual cancer was predictive of prostate-specific antigen recurrence in multivariable analysis.

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

    Science.gov (United States)

    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, 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.

  6. A Survey of Knowledge About and Perceived Barriers to Prostate Cancer Screening Among Medical Staff

    Directory of Open Access Journals (Sweden)

    Akbarizadeh

    2016-04-01

    Full Text Available Background Prostate cancer is the most common cancer among men and the second leading cause of deaths from cancer. Results of previous studies indicate the effectiveness of screening and early detection in reducing mortality from this disease. Objectives The purpose of this study was to survey the knowledge about prostate cancer and perceived barriers to prostate cancer screening among medical staff of two universities in Ahvaz, Iran. Materials and Methods This cross-sectional descriptive study was performed on 120 employees over 40 years old at Ahvaz Jundishapur University of Medical Sciences and Shahid Chamran University of Ahvaz, who were selected by using simple random sampling. The data collection tool was a researcher-created questionnaire based on the study of texts and other studies. Data analysis was performed using SPSS software and through analytical methods including descriptive and inferential statistics. Results The most common barriers to screening for prostate cancer were a lack of knowledge about where to go for tests and how screening tests are done (70.8%, a lack of emphasis on screening tests (59.1%, and a fear of thinking about the disease (50%. Results showed that there was no significant relationship between doing the serum antigen test and having knowledge regarding prostate cancer. But there was a significant association between prostate cancer screening and perceived barriers (P = 0.001. Conclusions Results showed that whereas knowledge by itself cannot guarantee men’s participation in prostate cancer screenings, perceived barriers can play an important role in discouraging men from cancer screening participation. Therefore, designing programs to address these barriers is very important.

  7. Multidisciplinary Functional MR Imaging for Prostate Cancer

    International Nuclear Information System (INIS)

    Kim, Jeong Kon; Jang, Yun Jin; Cho, Gyung Goo

    2009-01-01

    Various functional magnetic resonance (MR) imaging techniques are used for evaluating prostate cancer including diffusion-weighted imaging, dynamic contrast- enhanced MR imaging, and MR spectroscopy. These techniques provide unique information that is helpful to differentiate prostate cancer from non-cancerous tissue and have been proven to improve the diagnostic performance of MRI not only for cancer detection, but also for staging, post-treatment monitoring, and guiding prostate biopsies. However, each functional MR imaging technique also has inherent challenges. Therefore, in order to make accurate diagnoses, it is important to comprehensively understand their advantages and limitations, histologic background related with image findings, and their clinical relevance for evaluating prostate cancer. This article will review the basic principles and clinical significance of functional MR imaging for evaluating prostate cancer

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

    Science.gov (United States)

    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

  9. Inverse probability of treatment-weighted competing risks analysis: an application on long-term risk of urinary adverse events after prostate cancer treatments.

    Science.gov (United States)

    Bolch, Charlotte A; Chu, Haitao; Jarosek, Stephanie; Cole, Stephen R; Elliott, Sean; Virnig, Beth

    2017-07-10

    To illustrate the 10-year risks of urinary adverse events (UAEs) among men diagnosed with prostate cancer and treated with different types of therapy, accounting for the competing risk of death. Prostate cancer is the second most common malignancy among adult males in the United States. Few studies have reported the long-term post-treatment risk of UAEs and those that have, have not appropriately accounted for competing deaths. This paper conducts an inverse probability of treatment (IPT) weighted competing risks analysis to estimate the effects of different prostate cancer treatments on the risk of UAE, using a matched-cohort of prostate cancer/non-cancer control patients from the Surveillance, Epidemiology and End Results (SEER) Medicare database. Study dataset included men age 66 years or older that are 83% white and had a median follow-up time of 4.14 years. Patients that underwent combination radical prostatectomy and external beam radiotherapy experienced the highest risk of UAE (IPT-weighted competing risks: HR 3.65 with 95% CI (3.28, 4.07); 10-yr. cumulative incidence = 36.5%). Findings suggest that IPT-weighted competing risks analysis provides an accurate estimator of the cumulative incidence of UAE taking into account the competing deaths as well as measured confounding bias.

  10. Vitamin D, PTH, and calcium in relation to survival following prostate cancer.

    Science.gov (United States)

    Brändstedt, Johan; Almquist, Martin; Manjer, Jonas; Malm, Johan

    2016-05-01

    Epidemiological studies suggest that low levels of vitamin D constitute a risk factor for prostate cancer. However, the results are conflicting, perhaps because prostate cancer is a very heterogeneous disease. More recent studies have focused on cancer progression and mortality. Vitamin D is closely related to both calcium metabolism and parathyroid hormone (PTH) levels, and all three factors have been implicated in prostate cancer. We examined the associations between pre-diagnostic serum levels of vitamin D (25OHD), PTH, and calcium and mortality among 943 participants within the Malmö Diet and Cancer Study, who were diagnosed with prostate cancer. The mean time from diagnosis until the end of followup was 9.1 years (SD 4.5), and the mean time from inclusion until end of follow-up was 16.6 years (SD 4.9). The analytes were divided into quartiles, and the risk of death from prostate cancer was analyzed using Cox proportional hazard analysis, yielding hazards ratios (HR) with 95 % confidence intervals. The models were adjusted for season and year of inclusion, age at baseline, age at diagnosis, body mass index (BMI), and tumor characteristics (TNM and Gleason score). We observed a trend toward a lower prostate-specific mortality with 25OHD >85 nmol/L in the unadjusted analysis. This became statistically significantly in the third quartile of 25OHD (85-102 nmol/L) compared to the first (L), HR 0.54 (0.34-0.85) when adjusting for age, time of inclusion, and BMI. The association was further strengthened when adjusted for age at diagnosis, Gleason score, and TNM classification with a HR in Q3 0.36 (0.22-0.60). p for trend was 0.03. Regarding calcium, there was a significantly lower HR for the second quartile (2.35-2.39 mmol/L) compared to the first (≤2.34 mmol/L) with a HR of 0.54 (0.32-0.86) in the unadjusted analysis. However, this association disappeared when adjusting for tumor characteristics. There were no associations between levels of PTH and prostate cancer

  11. Can the Mediterranean diet prevent prostate cancer?

    Science.gov (United States)

    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.

  12. Prostate stromal cell telomere shortening is associated with risk of prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial.

    Science.gov (United States)

    Heaphy, Christopher M; Gaonkar, Gaurav; Peskoe, Sarah B; Joshu, Corinne E; De Marzo, Angelo M; Lucia, M Scott; Goodman, Phyllis J; Lippman, Scott M; Thompson, Ian M; Platz, Elizabeth A; Meeker, Alan K

    2015-08-01

    Telomeres are repetitive nucleoproteins that help maintain chromosomal stability by inhibiting exonucleolytic degradation, prohibiting inappropriate homologous recombination, and preventing chromosomal fusions by suppressing double-strand break signals. We recently observed that men treated for clinically localized prostate cancer with shorter telomeres in their cancer-associated stromal cells, in combination with greater variation in cancer cell telomere lengths, were significantly more likely to progress to distant metastases, and die from their disease. Here, we hypothesized that shorter stromal cell telomere length would be associated with prostate cancer risk at time of biopsy. Telomere-specific fluorescence in situ hybridization (FISH) analysis was performed in normal-appearing stromal, basal epithelial, and luminal epithelial cells in biopsies from men randomized to the placebo arm of the Prostate Cancer Prevention Trial. Prostate cancer cases (N = 32) were either detected on a biopsy performed for cause or at the end of the study per trial protocol, and controls (N = 50), defined as negative for cancer on an end-of-study biopsy performed per trial protocol (e.g., irrespective of indication), were sampled. Logistic regression was used to estimate the association between mean telomere length of the particular cell populations, cell-to-cell telomere length variability, and risk of prostate cancer. Men with short stromal cell telomere lengths (below median) had 2.66 (95% CI 1.04-3.06; P = 0.04) times the odds of prostate cancer compared with men who had longer lengths (at or above median). Conversely, we did not observe statistically significant associations for short telomere lengths in normal-appearing basal (OR = 2.15, 95% CI 0.86-5.39; P= 0 .10) or luminal (OR = 1.15, 95% CI 0.47-2.80; P = 0.77) cells. These findings suggest that telomere shortening in normal stromal cells is associated with prostate cancer risk. It is essential

  13. Adjuvant radiotherapy for pathologically advanced prostate cancer a randomized clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Ian, M.; Thompson, J.R.; Catherine, M.; Tangen, P.H.; Paradelo, J.; Scott Lucia, M.; Miller, G.; Troyer, D.; Messing, E.; Forman, J.; Chin, J.; Swanson, G.; Canby-Hagino, E.; Crawford, E.D

    2008-01-15

    Context - Despite a stage-shift to earlier cancer stages and lower tumor volumes for prostate cancer, pathologically advanced disease is detected at radical prostatectomy in 38% to 52% of patients. However, the optimal management of these patients after radical prostatectomy is unknown. Objective - To determine whether adjuvant radiotherapy improves metastasis-free survival in patients with stage pT3 NO MO prostate cancer. Design, Setting, and Patients - Randomized, prospective, multi-institutional, US clinical trial with enrollment between August 15, 1988, and January 1, 1997 (with database frozen for statistical analysis on September 21, 2005). Patients were 425 men with pathologically advanced prostate cancer who had undergone radical prostatectomy. Intervention - Men were randomly assigned to receive 60 to 64 Gy of external beam radiotherapy delivered to the prostatic fossa (n = 214) or usual care plus observation (n = 211). Main Outcome Measures - Primary outcome was metastasis-free survival, defined as time to first occurrence of metastatic disease or death due to any cause. Secondary outcomes included prostate-specific antigen (PSA) relapse, recurrence-free survival, overall survival, freedom from hormonal therapy, and postoperative complications. Results - Among the 425 men, median follow-up was 10.6 years (inter-quartile range, 9.2-12.7 years). For metastasis-free survival,76 (35.5%) of 214 men in the adjuvant radiotherapy group were diagnosed with metastatic disease or died (median metastasis-free estimate, 14.7 years), compared with 91 (43.1%) of 211 (median metastasis-free estimate, 13.2 years) of those in the observation group (hazard ratio [HR], 0.75; 95% CI, 0.55-1.02; P = .06). There were no significant between-group differences for overall survival (71 deaths, median survival of 14.7 years for radiotherapy vs 83 deaths, median survival of 13.8 years for observation; HR, 0.80; 95% Cl, 0.58-1.09; P =.16). PSA relapse (median PSA relapse-free survival

  14. Adjuvant radiotherapy for pathologically advanced prostate cancer a randomized clinical trial

    International Nuclear Information System (INIS)

    Ian, M.; Thompson, J.R.; Catherine, M.; Tangen, P.H.; Paradelo, J.; Scott Lucia, M.; Miller, G.; Troyer, D.; Messing, E.; Forman, J.; Chin, J.; Swanson, G.; Canby-Hagino, E.; Crawford, E.D.

    2008-01-01

    Context - Despite a stage-shift to earlier cancer stages and lower tumor volumes for prostate cancer, pathologically advanced disease is detected at radical prostatectomy in 38% to 52% of patients. However, the optimal management of these patients after radical prostatectomy is unknown. Objective - To determine whether adjuvant radiotherapy improves metastasis-free survival in patients with stage pT3 NO MO prostate cancer. Design, Setting, and Patients - Randomized, prospective, multi-institutional, US clinical trial with enrollment between August 15, 1988, and January 1, 1997 (with database frozen for statistical analysis on September 21, 2005). Patients were 425 men with pathologically advanced prostate cancer who had undergone radical prostatectomy. Intervention - Men were randomly assigned to receive 60 to 64 Gy of external beam radiotherapy delivered to the prostatic fossa (n = 214) or usual care plus observation (n = 211). Main Outcome Measures - Primary outcome was metastasis-free survival, defined as time to first occurrence of metastatic disease or death due to any cause. Secondary outcomes included prostate-specific antigen (PSA) relapse, recurrence-free survival, overall survival, freedom from hormonal therapy, and postoperative complications. Results - Among the 425 men, median follow-up was 10.6 years (inter-quartile range, 9.2-12.7 years). For metastasis-free survival,76 (35.5%) of 214 men in the adjuvant radiotherapy group were diagnosed with metastatic disease or died (median metastasis-free estimate, 14.7 years), compared with 91 (43.1%) of 211 (median metastasis-free estimate, 13.2 years) of those in the observation group (hazard ratio [HR], 0.75; 95% CI, 0.55-1.02; P = .06). There were no significant between-group differences for overall survival (71 deaths, median survival of 14.7 years for radiotherapy vs 83 deaths, median survival of 13.8 years for observation; HR, 0.80; 95% Cl, 0.58-1.09; P =.16). PSA relapse (median PSA relapse-free survival

  15. Salvage radical prostatectomy for radiation-recurrent prostate cancer: a multi-institutional collaboration.

    Science.gov (United States)

    Chade, Daher C; Shariat, Shahrokh F; Cronin, Angel M; Savage, Caroline J; Karnes, R Jeffrey; Blute, Michael L; Briganti, Alberto; Montorsi, Francesco; van der Poel, Henk G; Van Poppel, Hendrik; Joniau, Steven; Godoy, Guilherme; Hurtado-Coll, Antonio; Gleave, Martin E; Dall'Oglio, Marcos; Srougi, Miguel; Scardino, Peter T; Eastham, James A

    2011-08-01

    Oncologic outcomes in men with radiation-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP) are poorly defined. To identify predictors of biochemical recurrence (BCR), metastasis, and death following SRP to help select patients who may benefit from SRP. This is a retrospective, international, multi-institutional cohort analysis. There was a median follow-up of 4.4 yr following SRP performed on 404 men with radiation-recurrent PCa from 1985 to 2009 in tertiary centers. Open SRP. BCR after SRP was defined as a serum prostate-specific antigen (PSA) ≥ 0.1 or ≥ 0.2 ng/ml (depending on the institution). Secondary end points included progression to metastasis and cancer-specific death. Median age at SRP was 65 yr of age, and median pre-SRP PSA was 4.5 ng/ml. Following SRP, 195 patients experienced BCR, 64 developed metastases, and 40 died from PCa. At 10 yr after SRP, BCR-free survival, metastasis-free survival, and cancer-specific survival (CSS) probabilities were 37% (95% confidence interval [CI], 31-43), 77% (95% CI, 71-82), and 83% (95% CI, 76-88), respectively. On preoperative multivariable analysis, pre-SRP PSA and Gleason score at postradiation prostate biopsy predicted BCR (p = 0.022; global p 75% of patients 10 yr after surgery. Patients with lower pre-SRP PSA levels and lower postradiation prostate biopsy Gleason score have the highest probability of cure from SRP. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  16. Prostate carcinoma: current diagnostic strategy

    International Nuclear Information System (INIS)

    Schwarzschild, Monica Maria Agata Stiepcich; Ferraz, Maria Lucia Cardoso Gomes; Oliveira, Jose Marcelo Amatuzzi; Andriolo, Adagmar

    2001-01-01

    Prostate cancer is the second cause of cancer death in men in the Western world. Despite progress in the treatment of advanced disease, it is recognized that the only possibility of reduction in prostate cancer death is nearly diagnosis when the disease is localized. In the present study our aim was to review the current strategy for diagnosis of prostate carcinoma. Prostate-specific antigen (PSA) is a valuable tumor marker and has demonstrated effectiveness in detecting prostate carcinoma, monitoring therapeutic efficacy, and disclosing disease recurrence. However, alternative methods are been proposed just as the free to total PSA ratio, PSA density, PSA velocity, which could improve the diagnostic sensibility and the specificity. Image diagnostic methods include transrectal ultra sound, computerized tomography, magnetic resonance image, and bone cintigraphy. The ultra sound is the best approach to guide the prostate biopsy and, together with the magnetic resonance is still useful for loco regional graduation. Computerized tomography as magnetic resonance image can be used for identification of linfonodal involvement. Bone cintigraphy is the best method for the identification of metastatic disease. (author)

  17. Long-term oncologic results of salvage radical prostatectomy for locally recurrent prostate cancer after radiotherapy

    International Nuclear Information System (INIS)

    Bianco, Fernando J.; Scardino, Peter T.; Stephenson, Andrew J.; DiBlasio, Christopher J.; Fearn, Paul A.; Eastham, James A.

    2005-01-01

    Purpose: Salvage radical prostatectomy (RP) may potentially cure patients who have isolated local prostate cancer recurrence after radiotherapy (RT). We report the long-term cancer control associated with salvage RP in a consecutive cohort of patients and identify the variables associated with disease progression and cancer survival. Methods and Materials: A total of 100 consecutive patients underwent salvage RP with curative intent for biopsy-confirmed, locally recurrent, prostate cancer after RT. Disease progression after salvage RP was defined as a prostate-specific antigen (PSA) level of ≥0.2 ng/mL or by initiation of androgen deprivation therapy. Cancer-specific mortality was defined as active clinical disease progression despite castration. Cox regression analysis was used to evaluate these endpoints. The median follow-up from RT was 10 years (range, 3-27 years) and from salvage RP was 5 years (range, 1-20 years). Results: Overall, the 5-year progression-free probability was 55% (95% confidence interval, 46-64%), and the median progression-free interval was 6.4 years. The preoperative PSA level was the only significant pretreatment predictor of disease progression in the multivariate analysis (p = 0.01). The 5-year progression-free probability for patients with a preoperative PSA level of 10 ng/mL was 86%, 55%, and 37%, respectively. The 10-year and 15-year cancer-specific mortality after salvage RP was 27% and 40%, respectively. The median time from disease progression to cancer-specific death was 10.3 years (95% confidence interval, 7.6-12.9). After multivariate analysis, the preoperative serum PSA level and seminal vesicle or lymph node status correlated independently with disease progression. Conclusions: Greater preoperative PSA levels are associated with disease progression and cancer-specific death. Long-term control of locally recurrent prostate cancer after definitive RT is possible when salvage RP is performed early in the course of recurrent

  18. Association of meat and coffee use with cancers of the large bowel, breast, and prostate among Seventh-Day Adventists: preliminary results.

    Science.gov (United States)

    Phillips, R L; Snowdon, D A

    1983-05-01

    Deaths from cancers of the large bowel, breast, and prostate were ascertained over a 21-year period among 21,295 white California Adventists. Compared to non-Adventists, the age-sex-adjusted mortality for large bowel cancer was substantially reduced among Adventists. Adventists also showed a minimum reduction in mortality for breast and prostate cancer. Fatal large bowel cancer within the Adventist group was unrelated to meat use. However, coffee use showed a substantial positive association with fatal large bowel cancer. Although this association may be indirect or spurious, it deserves further investigation. Weak nonsignificant associations were observed between cancers of the breast and prostate and meat use.

  19. Unfoldomics of prostate cancer: on the abundance and roles of intrinsically disordered proteins in prostate cancer

    Science.gov (United States)

    Landau, Kevin S; Na, Insung; Schenck, Ryan O; Uversky, Vladimir N

    2016-01-01

    Prostatic diseases such as prostate cancer and benign prostatic hyperplasia are highly prevalent among men. The number of studies focused on the abundance and roles of intrinsically disordered proteins in prostate cancer is rather limited. The goal of this study is to analyze the prevalence and degree of disorder in proteins that were previously associated with the prostate cancer pathogenesis and to compare these proteins to the entire human proteome. The analysis of these datasets provides means for drawing conclusions on the roles of disordered proteins in this common male disease. We also hope that the results of our analysis can potentially lead to future experimental studies of these proteins to find novel pathways associated with this disease. PMID:27453073

  20. Is there a link between BPH and prostate cancer?

    Science.gov (United States)

    Chang, R T M; Kirby, Roger; Challacombe, B J

    2012-04-01

    BPH is one of the most common diseases of older men, with more than 70% of men over 70 years affected, and prostate cancer is the most common cancer in men in the UK. Prostate cancer generally presents in one of three ways: asymptomatic patients who are screened (usually by a PSA test); men with LUTS who are investigated and undergo prostate biopsy; or patients with symptoms of metastasis such as bone pain. Men can be reassured that the main cause of LUTS is BPH. Only a small proportion of men have LUTS that are directly attributable to prostate cancer. Digital rectal examination (DRE) gives an evaluation of prostate size, which is relevant in particular to BPH management, and along with PSA testing it is one of the only ways of differentiating clinically between BPH and prostate cancer. If a nodular abnormality is present there is around a 50% chance of a diagnosis of prostate cancer being made on biopsy. Raised levels of serum PSA may be suggestive of prostate cancer, but diagnosis requires histological confirmation in almost every case. A normal PSA, PSA density and DRE can give reasonable confidence with regards to excluding clinically significant prostate cancer. BPH is not a known risk factor for prostate cancer, although the two frequently coexist. Age is the strongest predictor of prostate cancer risk, along with family history. BPH is not considered to be a precursor of prostate cancer. It is likely that although BPH may not make prostate cancer more likely to occur, it may increase the chance of diagnosing an incidental cancer.

  1. Prostate resonance imaging: morphology and metabolism

    International Nuclear Information System (INIS)

    Ocantos, Jorge A.; Pietrani, Marcelo A.; Paganini, Lisandro

    2007-01-01

    The cancer of prostate is the most frequent neoplasms and the third cause of death in men, although the average of survival of patients it improved, the cancer of prostate is an important problem in health. The majority of these tumors are of slow growth and the early detection allows high probabilities of definitive treatment. The neoplasms of prostate detected at present are smaller than the detected ones 20 years ago behind, nevertheless exist big differences in the aggressiveness of these tumors. The images are very important in the management of prostate cancer, and the magnetic resonance imaging of the prostate is a new tool in the evaluation of prostate cancer [es

  2. Focal therapy in prostate cancer

    NARCIS (Netherlands)

    van den Bos, W.

    2016-01-01

    Interesting developments took place in the treatment of prostate cancer including focal therapy for less aggressive organ-confined prostate cancer. Fortunately, curative treatment is often still an option for patients suffering from the lower staged tumors. In carefully selected patients, the

  3. Matrix-Dependent Regulation of AKT in Hepsin-Overexpressing PC3 Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Stephanie M Wittig-Blaich

    2011-07-01

    Full Text Available 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.

  4. MicroRNAs as New Characters in the Plot between Epigenetics and Prostate Cancer

    OpenAIRE

    Paone, Alessio; Galli, Roberta; Fabbri, Muller

    2011-01-01

    Prostate cancer (PCA) still represents a leading cause of death. An increasing number of studies have documented that microRNAs (miRNAs), a subgroup of non-coding RNAs with gene regulatory functions, are differentially expressed in PCA respect to the normal tissue counterpart, suggesting their involvement in prostate carcinogenesis and dissemination. Interestingly, it has been shown that miRNAs undergo the same regulatory mechanisms than any other protein coding gene, including epigenetic reg...

  5. REVIEW ARTICLE: PROSTATE CANCER SCREENING USING ...

    African Journals Online (AJOL)

    FOBUR

    ABSTRACT. Background: Prostate cancer is the commonest cancer among men in Nigeria and early detection is key to cure and survival but its screening through prostate specific antigen (PSA) has remain controversial in literature. Screening with prostate specific antigen (PSA) has led to more men diagnosed with ...

  6. Prostate-Specific Membrane Antigen Targeted Gold Nanoparticles for Theranostics of Prostate Cancer.

    Science.gov (United States)

    Mangadlao, Joey Dacula; Wang, Xinning; McCleese, Christopher; Escamilla, Maria; Ramamurthy, Gopalakrishnan; Wang, Ziying; Govande, Mukul; Basilion, James P; Burda, Clemens

    2018-04-24

    Prostate cancer is one of the most common cancers and among the leading causes of cancer deaths in the United States. Men diagnosed with the disease typically undergo radical prostatectomy, which often results in incontinence and impotence. Recurrence of the disease is often experienced by most patients with incomplete prostatectomy during surgery. Hence, the development of a technique that will enable surgeons to achieve a more precise prostatectomy remains an open challenge. In this contribution, we report a theranostic agent (AuNP-5kPEG-PSMA-1-Pc4) based on prostate-specific membrane antigen (PSMA-1)-targeted gold nanoparticles (AuNPs) loaded with a fluorescent photodynamic therapy (PDT) drug, Pc4. The fabricated nanoparticles are well-characterized by spectroscopic and imaging techniques and are found to be stable over a wide range of solvents, buffers, and media. In vitro cellular uptake experiments demonstrated significantly higher nanoparticle uptake in PSMA-positive PC3pip cells than in PSMA-negative PC3flu cells. Further, more complete cell killing was observed in Pc3pip than in PC3flu cells upon exposure to light at different doses, demonstrating active targeting followed by Pc4 delivery. Likewise, in vivo studies showed remission on PSMA-expressing tumors 14 days post-PDT. Atomic absorption spectroscopy revealed that targeted AuNPs accumulate 4-fold higher in PC3pip than in PC3flu tumors. The nanoparticle system described herein is envisioned to provide surgical guidance for prostate tumor resection and therapeutic intervention when surgery is insufficient.

  7. Prostate Brachytherapy in Men ≥75 Years of Age

    International Nuclear Information System (INIS)

    Merrick, Gregory S.; Wallner, Kent E.; Galbreath, Robert W.; Butler, Wayne M.; Brammer, Sarah G.; Allen, Zachariah A.; Adamovich, Edward

    2008-01-01

    Purpose: To evaluate cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) in prostate cancer patients aged ≥75 years undergoing brachytherapy with or without supplemental therapies. Methods and Materials: Between April 1995 and August 2004, 145 consecutive patients aged ≥75 years underwent permanent prostate brachytherapy. Median follow-up was 5.8 years. Biochemical progression-free survival was defined by a prostate-specific antigen level ≤0.40 ng/mL after nadir. Patients with metastatic prostate cancer or hormone-refractory disease without obvious metastases who died of any cause were classified as dead of prostate cancer. All other deaths were attributed to the immediate cause of death. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on survival. Results: Nine-year CSS, bPFS, and OS rates for the entire cohort were 99.3%, 97.1%, and 64.5%, respectively. None of the evaluated parameters predicted for CSS, whereas bPFS was most closely predicted by percentage positive biopsies. Overall survival and non-cancer deaths were best predicted by tobacco status. Thirty-seven patients have died, with 83.8% of the deaths due to cardiovascular disease (22 patients) or second malignancies (9 patients). To date, only 1 patient (0.7%) has died of metastatic prostate cancer. Conclusions: After brachytherapy, high rates of CSS and bPFS are noted in elderly prostate cancer patients. Overall, approximately 65% of patients are alive at 9 years, with survival most closely related to tobacco status. We believe our results support an aggressive locoregional approach in appropriately selected elderly patients

  8. Survival Following Radiation and Androgen Suppression Therapy for Prostate Cancer in Healthy Older Men: Implications for Screening Recommendations

    International Nuclear Information System (INIS)

    Nguyen, Paul L.; Chen, Ming-Hui; Renshaw, Andrew A.; Loffredo, Marian; Kantoff, Philip W.; D'Amico, Anthony V.

    2010-01-01

    Purpose: The U.S. Preventive Services Task Force has recommended against screening men over 75 for prostate cancer. We examined whether older healthy men could benefit from aggressive prostate cancer treatment. Methods and Materials: 206 men with intermediate to high risk localized prostate cancer randomized to 70 Gy of radiation (RT) or RT plus 6 months of androgen suppression therapy (RT+AST) constituted the study cohort. Within subgroups stratified by Adult Comorbidity Evaluation-27 comorbidity score and age, Cox multivariable analysis was used to determine whether treatment with RT+AST as compared with RT was associated with a decreased risk of death. Results: Among healthy men (i.e., with mild or no comorbidity), 78 were older than the median age of 72.4 years, and in this subgroup, RT+AST was associated with a significantly lower risk of death on multivariable analysis (adjusted hazard ratio = 0.36 (95% CI=0.13-0.98), p = 0.046, with significantly lower 8-year mortality estimates of 16.5% vs. 41.4% (p = 0.011). Conversely, among men with moderate or severe comorbidity, 24 were older than the median age of 73, and in this subgroup, treatment with RT+AST was associated with a higher risk of death (adjusted hazard ratio = 5.2 (1.3-20.2), p = 0.018). Conclusion: In older men with mild or no comorbidity, treatment with RT+AST was associated with improved survival compared with treatment with RT alone, suggesting that healthy older men may derive the same benefits from prostate cancer treatment as younger men. We therefore suggest that prostate cancer screening recommendations should not be based on strict age cutoffs alone but should also take into account comorbidity.

  9. Management of patients with advanced prostate cancer

    DEFF Research Database (Denmark)

    Gillessen, S; Omlin, A; Attard, G

    2015-01-01

    The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration......-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion...

  10. Hypoxia inducible factor-1α-dependent epithelial to mesenchymal transition under hypoxic conditions in prostate cancer cells.

    Science.gov (United States)

    Li, Mingchuan; Wang, Yong Xing; Luo, Yong; Zhao, Jiahui; Li, Qing; Zhang, Jiao; Jiang, Yongguang

    2016-07-01

    Prostate cancer is the most commonly diagnosed cancer in men and the second leading cause of cancer death. Hypoxia is an environmental stimulus that plays an important role in the development and cancer progression especially for solid tumors. The key regulator under hypoxic conditions is stabilized hypoxia-inducible factor (HIF)-1α. In the present study, immune-fluorescent staining, siRNAs, qRT-PC, immunoblotting, cell migration and invasion assays were carried out to test typical epithelial to mesenchymal transition under hypoxia and the key regulators of this process in PC3, a human prostate cancer cell line. Our data demonstrated that hypoxia induces diverse molecular, phenotypic and functional changes in prostate cancer cells that are consistent with EMT. We also showed that a cell signal factor such as HIF-1α, which might be stabilized under hypoxic environment, is involved in EMT and cancer cell invasive potency. The induced hypoxia could be blocked by HIF-1α gene silencing and reoxygenation of EMT in prostate cancer cells, hypoxia partially reversed accompanied by a process of mesenchymal-epithelial reverting transition (MErT). EMT might be induced by activation of HIF-1α-dependent cell signaling in hypoxic prostate cancer cells.

  11. Height, selected genetic markers and prostate cancer risk

    DEFF Research Database (Denmark)

    Lophatananon, Artitaya; Stewart-Brown, Sarah; Kote-Jarai, Zsofia

    2017-01-01

    Background:Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer.Methods:We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases...... and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions.Results:The results suggest that height is associated with high-grade prostate cancer risk. Men with height >180 cm...... are at a 22% increased risk as compared to men with height prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer...

  12. Prostate-Specific G-Protein Coupled Receptor, an Emerging Biomarker Regulating Inflammation and Prostate Cancer Invasion.

    Science.gov (United States)

    Rodriguez, M; Siwko, S; Liu, M

    2016-01-01

    Prostate cancer is highly prevalent among men in developed countries, but a significant proportion of detected cancers remain indolent, never progressing into aggressive carcinomas. This highlights the need to develop refined biomarkers that can distinguish between indolent and potentially dangerous cases. The prostate-specific G-protein coupled receptor (PSGR, or OR51E2) is an olfactory receptor family member with highly specific expression in human prostate epithelium that is highly overexpressed in PIN and prostate cancer. PSGR has been functionally implicated in prostate cancer cell invasiveness, suggesting a potential role in the transition to metastatic PCa. Recently, transgenic mice overexpressing PSGR in the prostate were reported to develop an acute inflammatory response followed by emergence of low grade PIN, whereas mice with compound PSGR overexpression and loss of PTEN exhibited accelerated formation of invasive prostate adenocarcinoma. This article will review recent PSGR findings with a focus on its role as a potential prostate cancer biomarker and regulator of prostate cancer invasion and inflammation.

  13. Vitamin D, Sunlight and Prostate Cancer Risk

    Directory of Open Access Journals (Sweden)

    Krishna Vanaja Donkena

    2011-01-01

    Full Text Available Prostate cancer is the second common cancer in men worldwide. The prevention of prostate cancer remains a challenge to researchers and clinicians. Here, we review the relationship of vitamin D and sunlight to prostate cancer risk. Ultraviolet radiation of the sunlight is the main stimulator for vitamin D production in humans. Vitamin D's antiprostate cancer activities may be involved in the actions through the pathways mediated by vitamin D metabolites, vitamin D metabolizing enzymes, vitamin D receptor (VDR, and VDR-regulated genes. Although laboratory studies including the use of animal models have shown that vitamin D has antiprostate cancer properties, whether it can effectively prevent the development and/or progression of prostate cancer in humans remains to be inconclusive and an intensively studied subject. This review will provide up-to-date information regarding the recent outcomes of laboratory and epidemiology studies on the effects of vitamin D on prostate cancer prevention.

  14. Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0512 TITLE: Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer PRINCIPAL INVESTIGATOR: Andrew...SUBTITLE 5a. CONTRACT NUMBER Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0512 5c. PROGRAM...blocked by the addition of Pim inhibitors. These results suggest that the Pim protein kinase can regulate stromal cell biology to modulate epithelial

  15. Cancer mortality and other causes of death in users of geothermal hot water.

    Science.gov (United States)

    Kristbjornsdottir, Adalbjorg; Rafnsson, Vilhjalmur

    2015-01-01

    Residents of geothermal areas have increased incidence of non-Hodgkin's lymphoma, breast, prostate, and kidney cancers. The aim was to study whether this is also reflected in cancer mortality among the population using geothermal hot water for space heating, washing, and showering. The follow-up was from 1981 to 2009. Personal identifier of those 5-64 years of age was used in record linkage with nationwide death registry. Thus, vital and emigration status was ascertained. The exposed population was defined as inhabitants of communities with district heating generated from geothermal wells since 1972. Reference populations were inhabitants of other areas with different degrees of volcanic/geothermal activity. Hazard ratio (HR) and 95% confidence intervals (CI) were adjusted for age, gender, education, housing, reproductive factors and smoking habits. Among those using geothermal water, the HR for all causes of death was 0.98 (95% CI 0.91-1.05) as compared with cold reference area. The HR for breast cancer was 1.53 (1.04-2.24), prostate cancer 1.74 (1.21-2.52), kidney cancer 1.78 (1.03-3.07), and for non-Hodgkin's lymphoma 2.01 (1.05-3.38). HR for influenza was 3.36 (1.32-8.58) and for suicide 1.49 (1.03-2.17). The significant excess mortality risk of breast and prostate cancers, and non-Hodgkin's lymphoma confirmed the results of similarly designed studies in Iceland on cancer incidence among populations from high-temperature geothermal areas and users of geothermal hot water. The risk is not confined to cancers with good prognosis, but also concerns fatal cancers. Further studies are needed on the chemical and physical content of the water and the environment emissions in geothermal areas.

  16. Prostate cancer

    International Nuclear Information System (INIS)

    Bey, P.; Beckendorf, V.; Stines, J.

    2001-01-01

    Radiation therapy of prostate carcinoma with a curative intent implies to treat the whole prostate at high dose (at least 66 Gy). According to clinical stage, PSA level, Gleason's score, the clinical target volume may include seminal vesicles and less often pelvic lymph nodes. Microscopic extra-capsular extension is found in 15 to 60% of T1-T2 operated on, specially in apex tumors. On contrary, cancers developing from the transitional zone may stay limited to the prostate even with a big volume and with a high PSA level. Zonal anatomy of the prostate identifies internal prostate, including the transitional zone (5% of the prostate in young people). External prostate includes central and peripheral zones. The inferior limit of the prostate is not lower than the inferior border of the pubic symphysis. Clinical and radiological examination: ultrasonography, nuclear magnetic resonance (NMR), CT-scan identify prognostic factors as tumor volume, capsule effraction, seminal vesicles invasion and lymph node extension. The identification of the clinical target volume is now done mainly by CT-Scan which identifies prostate and seminal vesicles. NMR could be helpful to identify more precisely prostate apex. The definition of margins around the clinical target volume has to take in account daily reproducibility and organ motion and of course the maximum tolerable dose for organs at risk. (authors)

  17. Haralick texture analysis of prostate MRI: utility for differentiating non-cancerous prostate from prostate cancer and differentiating prostate cancers with different Gleason scores

    Energy Technology Data Exchange (ETDEWEB)

    Wibmer, Andreas; Hricak, Hedvig; Sala, Evis; Vargas, Hebert Alberto [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York City, NY (United States); Gondo, Tatsuo; Matsumoto, Kazuhiro; Eastham, James [Memorial Sloan Kettering Cancer Center, Department of Urology, New York City, NY (United States); Veeraraghavan, Harini; Fehr, Duc [Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York City, NY (United States); Zheng, Junting; Goldman, Debra; Moskowitz, Chaya [Memorial Sloan Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York City, NY (United States); Fine, Samson W.; Reuter, Victor E. [Memorial Sloan Kettering Cancer Center, Department of Pathology, New York City, NY (United States)

    2015-10-15

    To investigate Haralick texture analysis of prostate MRI for cancer detection and differentiating Gleason scores (GS). One hundred and forty-seven patients underwent T2- weighted (T2WI) and diffusion-weighted prostate MRI. Cancers ≥0.5 ml and non-cancerous peripheral (PZ) and transition (TZ) zone tissue were identified on T2WI and apparent diffusion coefficient (ADC) maps, using whole-mount pathology as reference. Texture features (Energy, Entropy, Correlation, Homogeneity, Inertia) were extracted and analysed using generalized estimating equations. PZ cancers (n = 143) showed higher Entropy and Inertia and lower Energy, Correlation and Homogeneity compared to non-cancerous tissue on T2WI and ADC maps (p-values: <.0001-0.008). In TZ cancers (n = 43) we observed significant differences for all five texture features on the ADC map (all p-values: <.0001) and for Correlation (p = 0.041) and Inertia (p = 0.001) on T2WI. On ADC maps, GS was associated with higher Entropy (GS 6 vs. 7: p = 0.0225; 6 vs. >7: p = 0.0069) and lower Energy (GS 6 vs. 7: p = 0.0116, 6 vs. >7: p = 0.0039). ADC map Energy (p = 0.0102) and Entropy (p = 0.0019) were significantly different in GS ≤3 + 4 versus ≥4 + 3 cancers; ADC map Entropy remained significant after controlling for the median ADC (p = 0.0291). Several Haralick-based texture features appear useful for prostate cancer detection and GS assessment. (orig.)

  18. Haralick texture analysis of prostate MRI: utility for differentiating non-cancerous prostate from prostate cancer and differentiating prostate cancers with different Gleason scores

    International Nuclear Information System (INIS)

    Wibmer, Andreas; Hricak, Hedvig; Sala, Evis; Vargas, Hebert Alberto; Gondo, Tatsuo; Matsumoto, Kazuhiro; Eastham, James; Veeraraghavan, Harini; Fehr, Duc; Zheng, Junting; Goldman, Debra; Moskowitz, Chaya; Fine, Samson W.; Reuter, Victor E.

    2015-01-01

    To investigate Haralick texture analysis of prostate MRI for cancer detection and differentiating Gleason scores (GS). One hundred and forty-seven patients underwent T2- weighted (T2WI) and diffusion-weighted prostate MRI. Cancers ≥0.5 ml and non-cancerous peripheral (PZ) and transition (TZ) zone tissue were identified on T2WI and apparent diffusion coefficient (ADC) maps, using whole-mount pathology as reference. Texture features (Energy, Entropy, Correlation, Homogeneity, Inertia) were extracted and analysed using generalized estimating equations. PZ cancers (n = 143) showed higher Entropy and Inertia and lower Energy, Correlation and Homogeneity compared to non-cancerous tissue on T2WI and ADC maps (p-values: <.0001-0.008). In TZ cancers (n = 43) we observed significant differences for all five texture features on the ADC map (all p-values: <.0001) and for Correlation (p = 0.041) and Inertia (p = 0.001) on T2WI. On ADC maps, GS was associated with higher Entropy (GS 6 vs. 7: p = 0.0225; 6 vs. >7: p = 0.0069) and lower Energy (GS 6 vs. 7: p = 0.0116, 6 vs. >7: p = 0.0039). ADC map Energy (p = 0.0102) and Entropy (p = 0.0019) were significantly different in GS ≤3 + 4 versus ≥4 + 3 cancers; ADC map Entropy remained significant after controlling for the median ADC (p = 0.0291). Several Haralick-based texture features appear useful for prostate cancer detection and GS assessment. (orig.)

  19. HUMAN PROSTATE CANCER RISK FACTORS

    Science.gov (United States)

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  20. Incidental Prostate Cancer in Patients Undergoing Radical Cystoprostatectomy for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Mustafa Hiroš

    2008-05-01

    Full Text Available The objective of this work is to verify the incidence of incidental prostate adenocarcinoma in patients who underwent radical cystoprostatectomy for invasive bladder carcinoma. We have retrospectively reviewed patients who underwent radical cystoprostatectomy for infiltrative bladder tumors in period between 2003 and 2007 year, 94 men with bladder cancer underwent radical cystoprostatectomy at Urology Clinic-University of Sarajevo Clinics Centre. Mean age of patients was 67 years, with age limits ranging between 48 and 79 years. Pathohystological evaluation was used for all specimens from RCP. We found that 9,57% of cystoprostatectomy specimens in patients with bladder cancer also contained incidental prostate cancer. This result was much lower than overall mean frequency of incidentally detected prostate cancer in other series of cystoprostatectomy cases (range, 23%-68%. In conclusion we recommended digital rectal examination (DRE and prostate-specific antigen (PSA test as part of the bladder cancer work up and complete removal of the prostate at cystoprostatectomy to prevent residual prostate cancer.

  1. Cancer Deaths due to Lack of Universal Access to Radiotherapy in the Brazilian Public Health System.

    Science.gov (United States)

    Mendez, L C; Moraes, F Y; Fernandes, G Dos S; Weltman, E

    2018-01-01

    Radiotherapy plays a fundamental role in the treatment of cancer. Currently, the Brazilian public health system cannot match the national radiotherapy demand and many patients requiring radiotherapy are never exposed to this treatment. This study estimated the number of preventable deaths in the public health system if access to radiotherapy was universal. Incidence rates for the year 2016 provided by Instituto Nacional de Cancer were used in this analysis. The number of untreated patients requiring radiotherapy was obtained through the difference between the total number of patients requiring radiotherapy and the total amount of delivered radiotherapy treatments in the public health system. The number of deaths for the three most common cancers in each gender due to radiotherapy shortage was calculated. Initially, the total number of patients per cancer type was divided in stages using Brazilian epidemiological data. Subsequently, previously published tree arm diagrams were used to define the rate of patients requiring radiotherapy in each specific clinical setting. Finally, the clinical benefit of radiotherapy in overall survival was extracted from studies with level 1 evidence. Over 596 000 cancer cases were expected in Brazil in 2016. The public health system covers more than 75% of the Brazilian population and an estimated 111 432 patients who required radiotherapy in 2016 did not receive this treatment. Breast, colorectal and cervix cancers are the most frequent malignant tumours in women and prostate, lung and colorectal in men. The number of deaths due to a radiotherapy shortage in the year 2016 for these types of cancer were: (i) breast: 1011 deaths in 10 years; (ii) cervix: 2006 deaths in 2 years; (iii) lung: 1206 deaths in 2 years; (iv) prostate, intermediate risk: 562 deaths in 13 years; high risk: 298 deaths in 10 years; (v) colorectal: 0 deaths, as radiotherapy has no proven benefit in overall survival. Thousands of cancer patients requiring

  2. Increase of Prostate Cancer Incidence in Martinique

    Directory of Open Access Journals (Sweden)

    Dominique Belpomme

    2011-01-01

    Full Text Available Prostate cancer incidence is steadily increasing in many developed countries. Because insular populations present unique ethnic, geographical, and environmental characteristics, we analyzed the evolution of prostate cancer age-adjusted world standardized incidence rates in Martinique in comparison with that of metropolitan France. We also compared prostate cancer incidence rates, and lifestyle-related and socioeconomic markers such as life expectancy, dietary energy, and fat supply and consumption, with those in other Caribbean islands, France, UK, Sweden, and USA. The incidence rate of prostate cancer in Martinique is one of the highest reported worldwide; it is continuously growing since 1985 in an exponential mode, and despite a similar screening detection process and lifestyle-related behaviour, it is constantly at a higher level than in metropolitan France. However, Caribbean populations that are genetically close to that of Martinique have generally much lower incidence of prostate cancer. We found no correlation between prostate cancer incidence rates, life expectancy, and diet westernization. Since the Caribbean African descent-associated genetic susceptibility factor would have remained constant during the 1980–2005, we suggest that in Martinique some environmental change including the intensive use of carcinogenic organochlorine pesticides might have occurred as key determinant of the persisting highly growing incidence of prostate cancer.

  3. IGF-Regulated Genes in Prostate Cancer

    National Research Council Canada - National Science Library

    Roberts, Charles

    2003-01-01

    We hypothesized that genes that are differentially expressed as a result of the decreased IGF-I receptor gene expression seen in metastatic prostate cancer contribute to prostate cancer progression...

  4. IGF-Regulated Genes in Prostate Cancer

    National Research Council Canada - National Science Library

    Roberts, Charles T., Jr

    2005-01-01

    We hypothesized that genes that are differentially expressed as a result of the decreased IGF-I receptor gene expression seen in metastatic prostate cancer contribute to prostate cancer progression...

  5. Prostate-specific antigen-based prostate cancer screening: Past and future.

    Science.gov (United States)

    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.

  6. Novel Hsp90 inhibitor NVP-AUY922 radiosensitizes prostate cancer cells.

    Science.gov (United States)

    Gandhi, Nishant; Wild, Aaron T; Chettiar, Sivarajan T; Aziz, Khaled; Kato, Yoshinori; Gajula, Rajendra P; Williams, Russell D; Cades, Jessica A; Annadanam, Anvesh; Song, Danny; Zhang, Yonggang; Hales, Russell K; Herman, Joseph M; Armour, Elwood; DeWeese, Theodore L; Schaeffer, Edward M; Tran, Phuoc T

    2013-04-01

    Outcomes for poor-risk localized prostate cancers treated with radiation are still insufficient. Targeting the "non-oncogene" addiction or stress response machinery is an appealing strategy for cancer therapeutics. Heat-shock-protein-90 (Hsp90), an integral member of this machinery, is a molecular chaperone required for energy-driven stabilization and selective degradation of misfolded "client" proteins, that is commonly overexpressed in tumor cells. Hsp90 client proteins include critical components of pathways implicated in prostate cancer cell survival and radioresistance, such as androgen receptor signaling and the PI3K-Akt-mTOR pathway. We examined the effects of a novel non-geldanamycin Hsp90 inhibitor, AUY922, combined with radiation (RT) on two prostate cancer cell lines, Myc-CaP and PC3, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γ-H2AX foci kinetics and client protein expression in pathways important for prostate cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined treatment (RT-AUY922) on the PI3K-Akt-mTOR and AR pathways in a hind-flank tumor graft model. We observed that AUY922 caused supra-additive radiosensitization in both cell lines at low nanomolar doses with enhancement ratios between 1.4-1.7 (p < 0.01). RT-AUY922 increased apoptotic cell death compared with either therapy alone, induced G 2-M arrest and produced marked changes in client protein expression. These results were confirmed in vivo, where RT-AUY922 combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in Myc-CaP and PC3 tumor grafts (both p < 0.0001). Our data suggest that combined RT-AUY922 therapy exhibits promising activity against prostate cancer cells, which should be investigated in clinical studies.

  7. Prostate cancer mortality reduction by prostate-specific antigen-based screening adjusted for nonattendance and contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC).

    Science.gov (United States)

    Roobol, Monique J; Kerkhof, Melissa; Schröder, Fritz H; Cuzick, Jack; Sasieni, Peter; Hakama, Matti; Stenman, Ulf Hakan; Ciatto, Stefano; Nelen, Vera; Kwiatkowski, Maciej; Lujan, Marcos; Lilja, Hans; Zappa, Marco; Denis, Louis; Recker, Franz; Berenguer, Antonio; Ruutu, Mirja; Kujala, Paula; Bangma, Chris H; Aus, Gunnar; Tammela, Teuvo L J; Villers, Arnauld; Rebillard, Xavier; Moss, Sue M; de Koning, Harry J; Hugosson, Jonas; Auvinen, Anssi

    2009-10-01

    Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm. To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination. We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162,243 men 55-69 yr of age randomised in seven participating centres of the ERSPC. Centres were also grouped according to the type of randomisation (ie, before or after informed written consent). Nonattendance was defined as nonattending the initial screening round in ERSPC. The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam. Relative risks (RRs) with 95% confidence intervals (CIs) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose. In the ITS analysis, the RR of PCa death in men allocated to the intervention arm relative to the control arm was 0.80 (95% CI, 0.68-0.96). Adjustment for nonattendance resulted in a RR of 0.73 (95% CI, 0.58-0.93), and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 (95% CI, 0.51-0.92) to 0.71 (95% CI, 0.55-0.93), respectively. Contamination data were obtained through extrapolation of single-centre data. No heterogeneity was found between the groups of centres. PSA screening reduces the risk of dying of PCa by up to 31% in men actually screened. This benefit should be weighed against a degree of overdiagnosis and overtreatment inherent in PCa screening.

  8. PCOTH, a novel gene overexpressed in prostate cancers, promotes prostate cancer cell growth through phosphorylation of oncoprotein TAF-Ibeta/SET.

    Science.gov (United States)

    Anazawa, Yoshio; Nakagawa, Hidewaki; Furihara, Mutsuo; Ashida, Shingo; Tamura, Kenji; Yoshioka, Hiroki; Shuin, Taro; Fujioka, Tomoaki; Katagiri, Toyomasa; Nakamura, Yusuke

    2005-06-01

    Through genome-wide cDNA microarray analysis coupled with microdissection of prostate cancer cells, we identified a novel gene, prostate collagen triple helix (PCOTH), showing overexpression in prostate cancer cells and its precursor cells, prostatic intraepithelial neoplasia (PIN). Immunohistochemical analysis using polyclonal anti-PCOTH antibody confirmed elevated expression of PCOTH, a 100-amino-acid protein containing collagen triple-helix repeats, in prostate cancer cells and PINs. Knocking down PCOTH expression by small interfering RNA (siRNA) resulted in drastic attenuation of prostate cancer cell growth, and concordantly, LNCaP derivative cells that were designed to constitutively express exogenous PCOTH showed higher growth rate than LNCaP cells transfected with mock vector, suggesting the growth-promoting effect of PCOTH on prostate cancer cell. To investigate the biological mechanisms of this growth-promoting effect, we applied two-dimensional differential gel electrophoresis (2D-DIGE) to analyze the phospho-protein fractions in LNCaP cells transfected with PCOTH. We found that the phosphorylation level of oncoprotein TAF-Ibeta/SET was significantly elevated in LNCaP cells transfected with PCOTH than control LNCaP cells, and these findings were confirmed by Western blotting and in-gel kinase assay. Furthermore, knockdown of endogenous TAF-Ibeta expression by siRNA also attenuated viability of prostate cancer cells as well. These findings suggest that PCOTH is involved in growth and survival of prostate cancer cells thorough, in parts, the TAF-Ibeta pathway, and that this molecule should be a promising target for development of new therapeutic strategies for prostate cancers.

  9. Immunotherapy and Immune Evasion in Prostate Cancer

    International Nuclear Information System (INIS)

    Thakur, Archana; Vaishampayan, Ulka; Lum, Lawrence G.

    2013-01-01

    Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies

  10. Immunotherapy and Immune Evasion in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Thakur, Archana, E-mail: thakur@karmanos.org; Vaishampayan, Ulka [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Lum, Lawrence G., E-mail: thakur@karmanos.org [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Department of Medicine, Wayne State University, Detroit, MI 48201 (United States); Department of Immunology and Microbiology, Wayne State University, Detroit, MI 48201 (United States)

    2013-05-24

    Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies.

  11. Optimizing the Management of High-Risk, Localized Prostate Cancer

    OpenAIRE

    Sundi, Debasish; Jeong, Byong Chang; Lee, Seung Bae; Han, Misop

    2012-01-01

    Prostate cancer has a high prevalence and a rising incidence in many parts of the world. Although many screen-detected prostate cancers may be indolent, prostate cancer remains a major contributor to mortality in men. Therefore, the appropriate diagnosis and treatment of localized prostate cancer with lethal potential are of great importance. High-risk, localized prostate cancer has multiple definitions. Treatment options that should be individualized to each patient include observation, radi...

  12. Long term results in radiotherapy of prostatic cancer

    International Nuclear Information System (INIS)

    Bagshaw, M.A.; Ray, G.R.; Cox, R.S.

    1987-01-01

    Discounting skin cancer, prostatic cancer remains second only to lung cancer in incidence in the United States. Colon Cancer is a close third. The incidence of lung cancer has started to decline slightly in the male, while prostatic cancer continues to increase, no doubt related to the aging of the population. Radiation therapy was first used in the treatment of prostatic cancer in the United States about 1915, having been introduced as intracavitary radium treatments by the American urologist, Hugh Young. External beam irradiation was used in the 1930's, but mostly for palliation of ureteral and vascular obstruction. Definitive use was first described by other investigators in the 1940's' however, attention changed to hormonal manipulation following Huggin's discovery of the dependency of prostate cancer on male hormone. Improved radiation therapy sources were invented, such as Cobalt 60 units, linear accelerators and betatrons, stimulated a reinvestigation of the definitive use of radiation therapy to prostate cancer in the 1950's. According to the current American College of Surgeon's survey of patterns of care of patients with prostate cancer, the use of external beam irradiation for the treatment of prostatic cancer has doubled in the United States during the past decade; however, apparently in Europe, hormone deprivation remains the therapeutic standard

  13. Active Surveillance Versus Watchful Waiting for Localized Prostate Cancer: A Model to Inform Decisions.

    Science.gov (United States)

    Loeb, Stacy; Zhou, Qinlian; Siebert, Uwe; Rochau, Ursula; Jahn, Beate; Mühlberger, Nikolai; Carter, H Ballentine; Lepor, Herbert; Braithwaite, R Scott

    2017-12-01

    An increasing proportion of prostate cancer is being managed conservatively. However, there are no randomized trials or consensus regarding the optimal follow-up strategy. To compare life expectancy and quality of life between watchful waiting (WW) versus different strategies of active surveillance (AS). A Markov model was created for US men starting at age 50, diagnosed with localized prostate cancer who chose conservative management by WW or AS using different testing protocols (prostate-specific antigen every 3-6 mo, biopsy every 1-5 yr, or magnetic resonance imaging based). Transition probabilities and utilities were obtained from the literature. Primary outcomes were life years and quality-adjusted life years (QALYs). Secondary outcomes include radical treatment, metastasis, and prostate cancer death. All AS strategies yielded more life years compared with WW. Lifetime risks of prostate cancer death and metastasis were, respectively, 5.42% and 6.40% with AS versus 8.72% and 10.30% with WW. AS yielded more QALYs than WW except in cohorts age >65 yr at diagnosis, or when treatment-related complications were long term. The preferred follow-up strategy was also sensitive to whether people value short-term over long-term benefits (time preference). Depending on the AS protocol, 30-41% underwent radical treatment within 10 yr. Extending the surveillance biopsy interval from 1 to 5 yr reduced life years slightly, with a 0.26 difference in QALYs. AS extends life more than WW, particularly for men with higher-risk features, but this is partly offset by the decrement in quality of life since many men eventually receive treatment. More intensive active surveillance protocols extend life more than watchful waiting, but this is partly offset by decrements in quality of life from subsequent treatment. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  14. Use of advanced treatment technologies among men at low risk of dying from prostate cancer.

    Science.gov (United States)

    Jacobs, Bruce L; Zhang, Yun; Schroeck, Florian R; Skolarus, Ted A; Wei, John T; Montie, James E; Gilbert, Scott M; Strope, Seth A; Dunn, Rodney L; Miller, David C; Hollenbeck, Brent K

    2013-06-26

    The use of advanced treatment technologies (ie, intensity-modulated radiotherapy [IMRT] and robotic prostatectomy) for prostate cancer is increasing. The extent to which these advanced treatment technologies have disseminated among patients at low risk of dying from prostate cancer is uncertain. To assess the use of advanced treatment technologies, compared with prior standards (ie, traditional external beam radiation treatment [EBRT] and open radical prostatectomy) and observation, among men with a low risk of dying from prostate cancer. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified a retrospective cohort of men diagnosed with prostate cancer between 2004 and 2009 who underwent IMRT (n = 23,633), EBRT (n = 3926), robotic prostatectomy (n = 5881), open radical prostatectomy (n = 6123), or observation (n = 16,384). Follow-up data were available through December 31, 2010. The use of advanced treatment technologies among men unlikely to die from prostate cancer, as assessed by low-risk disease (clinical stage ≤T2a, biopsy Gleason score ≤6, and prostate-specific antigen level ≤10 ng/mL), high risk of noncancer mortality (based on the predicted probability of death within 10 years in the absence of a cancer diagnosis), or both. In our cohort, the use of advanced treatment technologies increased from 32% (95% CI, 30%-33%) to 44% (95% CI, 43%-46%) among men with low-risk disease (P risk of noncancer mortality (P use of these advanced treatment technologies among men with both low-risk disease and high risk of noncancer mortality increased from 25% (95% CI, 23%-28%) to 34% (95% CI, 31%-37%) (P use of advanced treatment technologies for men unlikely to die from prostate cancer increased from 13% (95% CI, 12%-14%), or 129.2 per 1000 patients diagnosed with prostate cancer, to 24% (95% CI, 24%-25%), or 244.2 per 1000 patients diagnosed with prostate cancer (P risk disease, high risk of noncancer mortality, or both, the use of

  15. The Role of Dietary Fat throughout the Prostate Cancer Trajectory

    Directory of Open Access Journals (Sweden)

    Katie M. Di Sebastiano

    2014-12-01

    Full Text Available Prostate cancer is the second most common cancer diagnosed world-wide; however, patients demonstrate exceptionally high survival rates. Many lifestyle factors, including obesity and diet, are considered risk factors for advanced prostate cancer. Dietary fat is a fundamental contributor to obesity and may be specifically important for prostate cancer patients. Prostate cancer treatment can result in changes in body composition, affecting quality of life for survivors by increasing the risk of co-morbidities, like cardiovascular disease and diabetes. We aim to examine dietary fat throughout the prostate cancer treatment trajectory, including risk, cancer development and survivorship. Focusing on one specific nutrient throughout the prostate cancer trajectory provides a unique perspective of dietary fat in prostate cancer and the mechanisms that may exacerbate prostate cancer risk, progression and recurrence. Through this approach, we noted that high intake of dietary fat, especially, high intake of animal and saturated fats, may be associated with increased prostate cancer risk. In contrast, a low-fat diet, specifically low in saturated fat, may be beneficial for prostate cancer survivors by reducing tumor angiogenesis and cancer recurrence. The insulin-like growth factor (IGF/Akt signaling pathway appears to be the key pathway moderating dietary fat intake and prostate cancer development and progression.

  16. Assessment of nucleosides as putative tumor biomarkers in prostate cancer screening by CE-UV.

    Science.gov (United States)

    Buzatto, Adriana Zardini; de Oliveira Silva, Mariana; Poppi, Ronei Jesus; Simionato, Ana Valéria Colnaghi

    2017-05-01

    Cancer is responsible for millions of deaths worldwide, but most base diseases may be cured if detected early. Screening tests may be used to identify early-stage malignant neoplasms. However, the major screening tool for prostate cancer, the prostate-specific antigen test, has unsuitable sensitivity. Since cancer cells may affect the pattern of consumption and excretion of nucleosides, such biomolecules are putative biomarkers that can be used for diagnosis and treatment evaluation. Using a previously validated method for the analysis of nucleosides in blood serum by capillary electrophoresis with UV-vis spectroscopy detection, we investigated 60 samples from healthy individuals and 42 samples from prostate cancer patients. The concentrations of nucleosides in both groups were compared and a multivariate partial least squares-discriminant analysis classification model was optimized for prediction of prostate cancer. The validation of the model with an independent sample set resulted in the correct classification of 82.4% of the samples, with sensitivity of 90.5% and specificity of 76.7%. A significant downregulation of 5-methyluridine and inosine was observed, which can be indicative of the carcinogenic process. Therefore, such analytes are potential candidates for prostate cancer screening. Graphical Abstract Separation of the studied nucleosides and the internal standard 8-Bromoguanosine by CE-UV (a); classification of the external validation samples (30 from healthy volunteers and 21 from prostate cancer patients) by the developed Partial Least Square - Discriminant Analysis (PLS-DA) model with accuracy of 82.4% (b); Receiver Operating Characteristics (ROC) curve (c); and Variable Importance in the Projection (VIP) values for the studied nucleosides (d). A significant down-regulation of 5- methyluridine (5mU) and inosine (I) was observed, which can be indicative of the presence of prostate tumors.

  17. Prostate cancer

    International Nuclear Information System (INIS)

    Spera, G.

    2010-01-01

    This work is about diagnosis, treatment and monitoring of prostate cancer. The techniques used are: transrectal ultrasound, laparascopy, bone scan, chest x-ray, radiography, chemoterapy and radiotherapy

  18. Local Progression among Men with Conservatively Treated Localized Prostate Cancer: Results from the Transatlantic Prostate Group

    Science.gov (United States)

    Eastham, James A.; Kattan, Michael W.; Fearn, Paul; Fisher, Gabrielle; Berney, Daniel M.; Oliver, Tim; Foster, Christopher S.; Møller, Henrik; Reuter, Victor; Cuzick, Jack; Scardino, Peter

    2009-01-01

    Objectives Men with clinically detected localized prostate cancer treated without curative intent are at risk of complications from local tumor growth. We investigated rates of local progression and need for local therapy among such men. Methods Men diagnosed with prostate cancer during 1990–1996 were identified from cancer registries throughout the United Kingdom. Inclusion criteria were age ≤76 yr at diagnosis, PSA level ≤100 ng/ml, and, within 6 mo after diagnosis, no radiation therapy, radical prostatectomy, evidence of metastatic disease, or death. Local progression was defined as increase in clinical stage from T1/2 to T3/T4 disease, T3 to T4 disease, and/or need for transurethral resection of the prostate (TURP) to relieve symptoms >6 mo after cancer diagnosis. Results The study included 2333 men with median follow-up of 85 mo (range: 6–174). Diagnosis was by TURP in 1255 men (54%), needle biopsy in 1039 (45%), and unspecified in 39 (2%). Only 29% were treated with hormonal therapy within 6 mo of diagnosis. Local progression occurred in 335 men, including 212 undergoing TURP. Factors most predictive of local progression on multivariable analysis were PSA at diagnosis and Gleason score of the diagnostic tissue (detrimental), and early hormonal therapy (protective). We present a nomogram that predicts the likelihood of local progression within 120 mo after diagnosis. Conclusions Men with clinically detected localized prostate cancer managed without curative intent have an approximately 15% risk for local progression within 10 yr of diagnosis. Among those with progression, the need for treatment is common, even among men diagnosed by TURP. When counseling men who are candidates for management without curative intent, the likelihood of symptoms from local progression must be considered. PMID:17544572

  19. Molecular Determinants of Hormone Refractory Prostate Cancer

    Science.gov (United States)

    2017-07-01

    receptor is no longer essential for survival, collectively termed androgen pathway independent prostate cancer (APIPC) (Nelson, 2012). A subset of these...Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer . Cancer Cell. 2011 May 17;19(5):575-86. Chen J, Li...2005a). The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer . Part 1: Modifications to the androgen receptor

  20. Factors driving inequality in prostate cancer survival: a population based study.

    Directory of Open Access Journals (Sweden)

    Richéal M Burns

    Full Text Available PURPOSE: As cancer control strategies have become more successful, issues around survival have become increasingly important to researchers and policy makers. The aim of this study was to examine the role of a range of clinical and socio-demographic variables in explaining variations in survival after a prostate cancer diagnosis, paying particular attention to the role of healthcare provider(s i.e. private versus public status. METHODS: Data were extracted from the National Cancer Registry Ireland, for patients diagnosed with prostate cancer from 1998-2009 (N = 26,183. A series of multivariate Cox and logistic regression models were used to examine the role of healthcare provider and socio-economic status (area-based deprivation on survival, controlling for age, stage, Gleason grade, marital status and region of residence. Survival was based on all-cause mortality. RESULTS: Older individuals who were treated in a private care setting were more likely to have survived than those who had not, when other factors were controlled for. Differences were evident with respect to marital status, region of residence, clinical stage and Gleason grade. The effect of socio-economic status was modified by healthcare provider, such that risk of death was higher in those men of lower socio-economic status treated by public, but not private providers in the Cox models. The logistic models revealed a socio-economic gradient in risk of death overall; the gradient was larger for those treated by public providers compared to those treated by private providers when controlling for a range of other confounding factors. CONCLUSION: The role of healthcare provider and socio-economic status in survival of men with prostate cancer may give rise to concerns that warrant further investigation.

  1. Emerging Therapies in Metastatic Prostate Cancer.

    Science.gov (United States)

    Sonnenburg, Daniel W; Morgans, Alicia K

    2018-04-11

    In the last decade, there have been multiple landmark therapeutic advances for the treatment of metastatic prostate cancer, both in the castration-resistant and hormone-sensitive setting. In this review, we highlight recent progress and ongoing trials for metastatic prostate cancer, including advances in chemotherapy, androgen receptor-directed therapy, targeted therapies, and immunotherapy. Several landmark studies for men with metastatic hormone-sensitive prostate cancer demonstrated improvement in overall survival with the addition of docetaxel chemotherapy or abiraterone acetate to standard androgen deprivation therapy. A single-arm phase 2 study of the PARP inhibitor olaparib demonstrated high response rates and more favorable progression-free and overall survival for men with metastatic castration-resistant prostate cancer and DNA repair defects treated with olaparib compared with men without DNA repair defects. Multiple ongoing clinical trials are investigating novel hormonal therapies and combinations of chemotherapy, targeted small molecules, immunotherapy, and radiopharmaceuticals. Progress continues to be made in the treatment of metastatic prostate cancer, and ongoing clinical trials continue to investigate novel agents and approaches to treatment.

  2. Are strict vegetarians protected against prostate cancer?

    Science.gov (United States)

    Tantamango-Bartley, Yessenia; Knutsen, Synnove F; Knutsen, Raymond; Jacobsen, Bjarne K; Fan, Jing; Beeson, W Lawrence; Sabate, Joan; Hadley, David; Jaceldo-Siegl, Karen; Penniecook, Jason; Herring, Patti; Butler, Terry; Bennett, Hanni; Fraser, Gary

    2016-01-01

    According to the American Cancer Society, prostate cancer accounts for ∼27% of all incident cancer cases among men and is the second most common (noncutaneous) cancer among men. The relation between diet and prostate cancer is still unclear. Because people do not consume individual foods but rather foods in combination, the assessment of dietary patterns may offer valuable information when determining associations between diet and prostate cancer risk. This study aimed to examine the association between dietary patterns (nonvegetarian, lacto-ovo-vegetarian, pesco-vegetarian, vegan, and semi-vegetarian) and prostate cancer incidence among 26,346 male participants of the Adventist Health Study-2. In this prospective cohort study, cancer cases were identified by matching to cancer registries. Cox proportional hazards regression analysis was performed to estimate HRs by using age as the time variable. In total, 1079 incident prostate cancer cases were identified. Around 8% of the study population reported adherence to the vegan diet. Vegan diets showed a statistically significant protective association with prostate cancer risk (HR: 0.65; 95% CI: 0.49, 0.85). After stratifying by race, the statistically significant association with a vegan diet remained only for the whites (HR: 0.63; 95% CI: 0.46, 0.86), but the multivariate HR for black vegans showed a similar but nonsignificant point estimate (HR: 0.69; 95% CI: 0.41, 1.18). Vegan diets may confer a lower risk of prostate cancer. This lower estimated risk is seen in both white and black vegan subjects, although in the latter, the CI is wider and includes the null. © 2016 American Society for Nutrition.

  3. A Review of the Potential of Phytochemicals from Prunus africana (Hook f. Kalkman Stem Bark for Chemoprevention and Chemotherapy of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Richard Komakech

    2017-01-01

    Full Text Available Prostate cancer remains one of the major causes of death worldwide. In view of the limited treatment options for patients with prostate cancer, preventive and treatment approaches based on natural compounds can play an integral role in tackling this disease. Recent evidence supports the beneficial effects of plant-derived phytochemicals as chemopreventive and chemotherapeutic agents for various cancers, including prostate cancer. Prunus africana has been used for generations in African traditional medicine to treat prostate cancer. This review examined the potential roles of the phytochemicals from P. africana, an endangered, sub-Saharan Africa plant in the chemoprevention and chemotherapy of prostate cancer. In vitro and in vivo studies have provided strong pharmacological evidence for antiprostate cancer activities of P. africana-derived phytochemicals. Through synergistic interactions between different effective phytochemicals, P. africana extracts have been shown to exhibit very strong antiandrogenic and antiangiogenic activities and have the ability to kill tumor cells via apoptotic pathways, prevent the proliferation of prostate cancer cells, and alter the signaling pathways required for the maintenance of prostate cancer cells. However, further preclinical and clinical studies ought to be done to advance and eventually use these promising phytochemicals for the prevention and chemotherapy of human prostate cancer.

  4. Automated prostate cancer detection via comprehensive multi-parametric magnetic resonance imaging texture feature models

    International Nuclear Information System (INIS)

    Khalvati, Farzad; Wong, Alexander; Haider, Masoom A.

    2015-01-01

    Prostate cancer is the most common form of cancer and the second leading cause of cancer death in North America. Auto-detection of prostate cancer can play a major role in early detection of prostate cancer, which has a significant impact on patient survival rates. While multi-parametric magnetic resonance imaging (MP-MRI) has shown promise in diagnosis of prostate cancer, the existing auto-detection algorithms do not take advantage of abundance of data available in MP-MRI to improve detection accuracy. The goal of this research was to design a radiomics-based auto-detection method for prostate cancer via utilizing MP-MRI data. In this work, we present new MP-MRI texture feature models for radiomics-driven detection of prostate cancer. In addition to commonly used non-invasive imaging sequences in conventional MP-MRI, namely T2-weighted MRI (T2w) and diffusion-weighted imaging (DWI), our proposed MP-MRI texture feature models incorporate computed high-b DWI (CHB-DWI) and a new diffusion imaging modality called correlated diffusion imaging (CDI). Moreover, the proposed texture feature models incorporate features from individual b-value images. A comprehensive set of texture features was calculated for both the conventional MP-MRI and new MP-MRI texture feature models. We performed feature selection analysis for each individual modality and then combined best features from each modality to construct the optimized texture feature models. The performance of the proposed MP-MRI texture feature models was evaluated via leave-one-patient-out cross-validation using a support vector machine (SVM) classifier trained on 40,975 cancerous and healthy tissue samples obtained from real clinical MP-MRI datasets. The proposed MP-MRI texture feature models outperformed the conventional model (i.e., T2w+DWI) with regard to cancer detection accuracy. Comprehensive texture feature models were developed for improved radiomics-driven detection of prostate cancer using MP-MRI. Using a

  5. Epidemiology of prostate cancer in Asian countries.

    Science.gov (United States)

    Kimura, Takahiro; Egawa, Shin

    2018-06-01

    The incidence of prostate cancer has been increasing worldwide in recent years. The GLOBOCAN project showed that prostate cancer was the second most frequently diagnosed cancer and the fifth leading cause of cancer mortality among men worldwide in 2012. This trend has been growing even in Asian countries, where the incidence had previously been low. However, the accuracy of data about incidence and mortality as a result of prostate cancer in some Asian countries is limited. The cause of this increasing trend is multifactorial. One possible explanation is changes in lifestyles due to more Westernized diets. The incidence is also statistically biased by the wide implementation of early detection systems and the accuracy of national cancer registration systems, which are still immature in most Asian countries. Mortality rate decreases in Australia, New Zealand and Japan since the 1990s are possibly due to the improvements in treatment and/or early detection efforts employed. However, this rate is increasing in the majority of other Asian countries. Studies of latent and incidental prostate cancer provide less biased information. The prevalence of latent and incidental prostate cancer in contemporary Japan and Korea is similar to those in Western countries, suggesting the influence of lifestyle changes on carcinogenesis. Many studies reported evidence of both congenital and acquired risk factors for carcinogenesis of prostate cancer. Recent changes in the acquired risk factors might be associated with the increasing occurrence of prostate cancer in Asian countries. This trend could continue, especially in developing Asian countries. © 2018 The Japanese Urological Association.

  6. The role of prostatitis in prostate cancer: meta-analysis.

    Directory of Open Access Journals (Sweden)

    Junyi Jiang

    Full Text Available OBJECTIVE: Use systematic review methods to quantify the association between prostatitis and prostate cancer, under both fixed and random effects model. EVIDENCE ACQUISITION: Case control studies of prostate cancer with information on prostatitis history. All studies published between 1990-2012, were collected to calculate a pooled odds ratio. SELECTION CRITERIA: the selection criteria are as follows: human case control studies; published from May 1990 to July 2012; containing number of prostatitis, and prostate cancer cases. EVIDENCE SYNTHESIS: In total, 20 case control studies were included. A significant association between prostatitis and prostate cancer was found, under both fixed effect model (pooled OR=1.50, 95%CI: 1.39-1.62, and random effects model (OR=1.64, 95%CI: 1.36-1.98. Personal interview based case control studies showed a high level of association (fixed effect model: pooled OR=1.59, 95%CI: 1.47-1.73, random effects model: pooled OR= 1.87, 95%CI: 1.52-2.29, compared with clinical based studies (fixed effect model: pooled OR=1.05, 95%CI: 0.86-1.28, random effects model: pooled OR= 0.98, 95%CI: 0.67-1.45. Additionally, pooled ORs, were calculated for each decade. In a fixed effect model: 1990's: OR=1.58, 95% CI: 1.35-1.84; 2000's: OR=1.59, 95% CI: 1.40-1.79; 2010's: OR=1.37, 95% CI: 1.22-1.56. In a random effects model: 1990's: OR=1.98, 95% CI: 1.08-3.62; 2000's: OR=1.64, 95% CI: 1.23-2.19; 2010's: OR=1.34, 95% CI: 1.03-1.73. Finally a meta-analysis stratified by each country was conducted. In fixed effect models, U.S: pooled OR =1.45, 95%CI: 1.34-1.57; China: pooled OR =4.67, 95%CI: 3.08-7.07; Cuba: pooled OR =1.43, 95%CI: 1.00-2.04; Italy: pooled OR =0.61, 95%CI: 0.13-2.90. In random effects model, U.S: pooled OR=1.50, 95%CI: 1.25-1.80; China: pooled OR =4.67, 95%CI: 3.08-7.07; Cuba: pooled OR =1.43, 95%CI: 1.00-2.04; Italy: pooled OR =0.61, 95%CI: 0.13-2.90. CONCLUSIONS: the present meta-analysis provides the statistical

  7. Radiation therapy for prostate cancer

    International Nuclear Information System (INIS)

    Nakamura, Katsumasa

    2001-01-01

    In Japan, where the mortality rate of prostate cancer is lower than in Western countries, radical prostatectomy or hormonal therapy has been applied more frequently than radiation therapy. However, the number of patients with prostate cancer has been increasing recently and the importance of radiation therapy has rapidly been recognized. Although there have been no randomized trials, results from several institutions in Western countries suggest that similar results of cancer control are achieved with either radiation therapy or radical prostatectomy. For higher-risk cases, conformal high-dose therapy or adjuvant hormonal therapy is more appropriate. In this article, the results of radiation therapy for prostate cancer were reviewed, with a view to the appropriate choice of therapy in Japan. (author)

  8. PSA testing for men at average risk of prostate cancer

    Directory of Open Access Journals (Sweden)

    Bruce K Armstrong

    2017-07-01

    Full Text Available Prostate-specific antigen (PSA testing of men at normal risk of prostate cancer is one of the most contested issues in cancer screening. There is no formal screening program, but testing is common – arguably a practice that ran ahead of the evidence. Public and professional communication about PSA screening has been highly varied and potentially confusing for practitioners and patients alike. There has been much research and policy activity relating to PSA testing in recent years. Landmark randomised controlled trials have been reported; authorities – including the 2013 Prostate Cancer World Congress, the Prostate Cancer Foundation of Australia, Cancer Council Australia, and the National Health and Medical Research Council – have made or endorsed public statements and/or issued clinical practice guidelines; and the US Preventive Services Task Force is revising its recommendations. But disagreement continues. The contention is partly over what the new evidence means. It is also a result of different valuing and prioritisation of outcomes that are hard to compare: prostate cancer deaths prevented (a small and disputed number; prevention of metastatic disease (somewhat more common; and side-effects of treatment such as incontinence, impotence and bowel trouble (more common again. A sizeable proportion of men diagnosed through PSA testing (somewhere between 20% and 50% would never have had prostate cancer symptoms sufficient to prompt investigation; many of these men are older, with competing comorbidities. It is a complex picture. Below are four viewpoints from expert participants in the evolving debate, commissioned for this cancer screening themed issue of Public Health Research & Practice. We asked the authors to respond to the challenge of PSA testing of asymptomatic, normal-risk men. They raise important considerations: uncertainty, harms, the trustworthiness and interpretation of the evidence, cost (e.g. of using multiparametric

  9. Epidural analgesia during open radical prostatectomy does not improve long-term cancer-related outcome: a retrospective study in patients with advanced prostate cancer.

    Directory of Open Access Journals (Sweden)

    Patrick Y Wuethrich

    Full Text Available BACKGROUND: A beneficial effect of regional anesthesia on cancer related outcome in various solid tumors has been proposed. The data on prostate cancer is conflicting and reports on long-term cancer specific survival are lacking. METHODS: In a retrospective, single-center study, outcomes of 148 consecutive patients with locally advanced prostate cancer pT3/4 who underwent retropubic radical prostatectomy (RRP with general anesthesia combined with intra- and postoperative epidural analgesia (n=67 or with postoperative ketorolac-morphine analgesia (n=81 were reviewed. The median observation time was 14.00 years (range 10.87-17.75 yrs. Biochemical recurrence (BCR-free, local and distant recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier technique. Multivariate Cox proportional-hazards regression models were used to analyze clinicopathologic variables associated with disease progression and death. RESULTS: The survival estimates for BCR-free, local and distant recurrence-free, cancer-specific survival and overall survival did not differ between the two groups (P=0.64, P=0.75, P=0.18, P=0.32 and P=0.07. For both groups, higher preoperative PSA (hazard ratio (HR 1.02, 95% confidence interval (CI 1.01-1.02, P<0.0001, increased specimen Gleason score (HR 1.24, 95% CI 1.06-1.46, P=0.007 and positive nodal status (HR 1.66, 95% CI 1.03-2.67, P=0.04 were associated with higher risk of BCR. Increased specimen Gleason score predicted death from prostate cancer (HR 2.46, 95% CI 1.65-3.68, P<0.0001. CONCLUSIONS: General anaesthesia combined with epidural analgesia did not reduce the risk of cancer progression or improve survival after RRP for prostate cancer in this group of patients at high risk for disease progression with a median observation time of 14.00 yrs.

  10. Studies of rhodamine-123: effect on rat prostate cancer and human prostate cancer cells in vitro.

    Science.gov (United States)

    Arcadi, J A; Narayan, K S; Techy, G; Ng, C P; Saroufeem, R M; Jones, L W

    1995-06-01

    The effect of the lipophilic, cationic dye, Rhodamine-123 (Rh-123), on prostate cancer in rats, and on three tumor cell lines in vitro is reported here. The general toxicity of Rh-123 in mice has been found to be minimal. Lobund-Wistar (L-W) rats with the autochthonous prostate cancer of Pollard were treated for six doses with Rh-123 at a dose of 15 mg/kg subcutaneously every other day. Microscopic examination of the tumors revealed cellular and acinar destruction. The effectiveness of Rh-123 as a cytotoxic agent was tested by clonogenic and viability assays in vitro with three human prostate cancer cell lines. Severe (60-95%) growth inhibition was observed following Rh-123 exposure for 2-5 days at doses as low as 1.6 micrograms/ml in all three prostate cancer cell lines.

  11. Matrix-Dependent Regulation of AKT in Hepsin-Overexpressing PC3 Prostate Cancer Cells12

    Science.gov (United States)

    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

  12. Prostate-specific antigen-positive extramammary Paget's disease--association with prostate cancer

    DEFF Research Database (Denmark)

    Hammer, Anne; Hager, Henrik; Steiniche, Torben

    2008-01-01

    Extramammary Paget's disease (EMPD) is a rare intraepidermal adenocarcinoma that primarily affects the anogenital region. Cases of EMPD reacting with PSA (prostate-specific antigen) have previously been associated with underlying prostate cancer. However, a recent case of EMPD in our department has...... led us to question the value of PSA as an indicator of underlying prostate cancer. Clinical and pathological data were obtained for 16 cases of EMPD. Formalin-fixed, paraffin-embedded tissue blocks from the primary skin lesions were investigated using PSA and other immunohistochemical markers. 5...... of the 16 cases of EMPD stained positive for PSA (2 women and 3 men). However, no reactivity was seen for the prostatic marker P501S. Three of the five patients had been diagnosed with internal malignant disease-two with prostate cancer, stage 1. Immunohistochemical investigations of the tumour specimens...

  13. The Prostate cancer Intervention Versus Observation Trial:VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy to watchful waiting for men with clinically localized prostate cancer.

    Science.gov (United States)

    Wilt, Timothy J; Brawer, Michael K; Barry, Michael J; Jones, Karen M; Kwon, Young; Gingrich, Jeffrey R; Aronson, William J; Nsouli, Imad; Iyer, Padmini; Cartagena, Ruben; Snider, Glenn; Roehrborn, Claus; Fox, Steven

    2009-01-01

    Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men. Ninety percent of men with prostate cancer are over aged 60 years, diagnosed by early detection with the prostate specific antigen (PSA) blood test and have disease believed confined to the prostate gland (clinically localized). Common treatments for clinically localized prostate cancer include watchful waiting surgery to remove the prostate gland (radical prostatectomy), external beam radiation therapy and interstitial radiation therapy (brachytherapy) and androgen deprivation. Little is known about the relative effectiveness and harms of treatments due to the paucity of randomized controlled trials. The VA/NCI/AHRQ Cooperative Studies Program Study #407: Prostate cancer Intervention Versus Observation Trial (PIVOT), initiated in 1994, is a multicenter randomized controlled trial comparing radical prostatectomy to watchful waiting in men with clinically localized prostate cancer. We describe the study rationale, design, recruitment methods and baseline characteristics of PIVOT enrollees. We provide comparisons with eligible men declining enrollment and men participating in another recently reported randomized trial of radical prostatectomy versus watchful waiting conducted in Scandinavia. We screened 13,022 men with prostate cancer at 52 United States medical centers for potential enrollment. From these, 5023 met initial age, comorbidity and disease eligibility criteria and a total of 731 men agreed to participate and were randomized. The mean age of enrollees was 67 years. Nearly one-third were African-American. Approximately 85% reported they were fully active. The median prostate specific antigen (PSA) was 7.8 ng/mL (mean 10.2 ng/mL). In three-fourths of men the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise. Using previously developed tumor risk categorizations incorporating PSA levels, Gleason

  14. Prostate specific antigen velocity does not aid prostate cancer detection in men with prior negative biopsy.

    Science.gov (United States)

    Vickers, Andrew J; Wolters, Tineke; Savage, Caroline J; Cronin, Angel M; O'Brien, M Frank; Roobol, Monique J; Aus, Gunnar; Scardino, Peter T; Hugosson, Jonas; Schröder, Fritz H; Lilja, Hans

    2010-09-01

    Prostate specific antigen velocity has been proposed as a marker to aid in prostate cancer detection. We determined whether prostate specific antigen velocity could predict repeat biopsy results in men with persistently increased prostate specific antigen after initial negative biopsy. We identified 1,837 men who participated in the Göteborg or Rotterdam section of the European Randomized Screening study of Prostate Cancer and who underwent 1 or more subsequent prostate biopsies after an initial negative finding. We evaluated whether prostate specific antigen velocity improved predictive accuracy beyond that of prostate specific antigen alone. Of the 2,579 repeat biopsies 363 (14%) were positive for prostate cancer, of which 44 (1.7%) were high grade (Gleason score 7 or greater). Prostate specific antigen velocity was statistically associated with cancer risk but had low predictive accuracy (AUC 0.55, p <0.001). There was some evidence that prostate specific antigen velocity improved AUC compared to prostate specific antigen for high grade cancer. However, the small increase in risk associated with high prostate specific antigen velocity (from 1.7% to 2.8% as velocity increased from 0 to 1 ng/ml per year) had questionable clinical relevance. Men with prior negative biopsy are at lower risk for prostate cancer at subsequent biopsies with high grade disease particularly rare. We found little evidence to support prostate specific antigen velocity to aid in decisions about repeat biopsy for prostate cancer. 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  15. Prevention of Prostate Cancer with Oleanane Synthetic Triterpenoid CDDO-Me in the TRAMP Mouse Model of Prostate Cancer

    International Nuclear Information System (INIS)

    Gao, Xiaohua; Deeb, Dorrah; Liu, Yongbo; Arbab, Ali S.; Divine, George W.; Dulchavsky, Scott A.; Gautam, Subhash C.

    2011-01-01

    2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), a synthetic analog of oleanolic acid, and its C28 methyl ester derivative (CDDO-Me), have shown potent antitumorigenic activity against a wide range of cancer cell lines, including prostate cancer cells in vitro, and inhibited the development of liver and lung cancer in vivo. In the present study, we examined the efficacy of CDDO-Me in preventing the development and progression of prostate cancer in the transgenic adenocarinoma of the mouse prostate (TRAMP) model. CDDO-Me inhibited the growth of murine TRAMPC-1 prostate cancer cells by inducing apoptosis through the inhibition of antiapoptotic p-Akt, p-mTOR and NF-κB. Early intervention with CDDO-Me (7.5 mg/kg) initiated at five weeks of age for 20 wk inhibited the progression of the preneoplastic lesions (low-grade PIN and high-grade-PIN) to adenocarcinoma in the dorsolateral prostate (DLP) and ventral prostate (VP) lobes of TRAMP mice. Even delayed administration of CDDO-Me started at 12 wk of age for 12 wk inhibited the development of adenocarcimona of the prostate. Both early and late treatment with CDDO-Me inhibited the metastasis of tumor to the distant organs. Treatment with CDDO-Me inhibited the expression of prosurvival p-Akt and NF-κB in the prostate and knocking-down Akt in TRAMPC-1 tumor cells sensitized them to CDDO-Me. These findings indicated that Akt is a target for apoptoxicity in TRAMPC-1 cells in vitro and potentially a target of CDDO-Me for inhibition of prostate cancer in vivo

  16. Chemopreventive Effects of Magnesium Chloride Supplementation on Hormone Independent Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Elsa Quiroz

    2016-01-01

    Full Text Available Background: Lifestyle significantly impacts the risk factors associated with prostate cancer, out of which diet appears to be the most influential. An emerging chemopreventive approach, which involves the adequate intake of dietary constituents, has shown great potential in preventing the occurrence or progression of cancer. Magnesium is known to be an essential cofactor for more than 300 enzymatic processes, and is responsible for the regulation of various cellular reactions in the body. A plethora of studies have shown evidence that changes in the intracellular levels of magnesium could contribute to cell proliferation and apoptosis in some normal and malignant cells. The aim of the study was to investigate the effects of magnesium chloride (MgCl2 in DU-145 prostate cancer cells. Methodology: Cultured DU-145 cells were subjected to graded concentrations or doses (50-500 µM of MgCl2 for 48 hours. The cell viability was assessed using MTT and Resazurin reduction assays. NBT assay was also used to assess the treatment-induced intracellular ROS levels. Acridine Orange/Ethidium Bromide (AcrO/EtBr and Rh123/EtBr fluorescent stains were used to assess the cell death type and mitochondrial membrane potential (Δψm respectively. Results: The results revealed a dose-dependent decrease (P < 0.05 in cell viability in treated DU-145 cells after 48 hours. The NBT assay also revealed a dose dependent biphasic response (P < 0.05 in intracellular levels of ROS. There was a drop (P < 0.05 in ROS levels in all groups except at 100 µM, where ROS level was higher than the control. Apoptosis was the primary mode of cell death as observed in the fluorescence analysis. Conclusion: Our finding suggests that MgCl2 may be potentially chemopreventive for prostate cancer. This justifies further studies into its mechanism of action in DU-145 and other prostate cancer cell types.

  17. Biomarker Discovery in Human Prostate Cancer: an Update in Metabolomics Studies

    Directory of Open Access Journals (Sweden)

    Ana Rita Lima

    2016-08-01

    Full Text Available Prostate cancer (PCa is the most frequently diagnosed cancer and the second leading cause of cancer death among men in Western countries. Current screening techniques are based on the measurement of serum prostate specific antigen (PSA levels and digital rectal examination. A decisive diagnosis of PCa is based on prostate biopsies; however, this approach can lead to false-positive and false-negative results. Therefore, it is important to discover new biomarkers for the diagnosis of PCa, preferably noninvasive ones. Metabolomics is an approach that allows the analysis of the entire metabolic profile of a biological system. As neoplastic cells have a unique metabolic phenotype related to cancer development and progression, the identification of dysfunctional metabolic pathways using metabolomics can be used to discover cancer biomarkers and therapeutic targets. In this study, we review several metabolomics studies performed in prostatic fluid, blood plasma/serum, urine, tissues and immortalized cultured cell lines with the objective of discovering alterations in the metabolic phenotype of PCa and thus discovering new biomarkers for the diagnosis of PCa. Encouraging results using metabolomics have been reported for PCa, with sarcosine being one of the most promising biomarkers identified to date. However, the use of sarcosine as a PCa biomarker in the clinic remains a controversial issue within the scientific community. Beyond sarcosine, other metabolites are considered to be biomarkers for PCa, but they still need clinical validation. Despite the lack of metabolomics biomarkers reaching clinical practice, metabolomics proved to be a powerful tool in the discovery of new biomarkers for PCa detection.

  18. Osteoporosis and prostate cancer

    DEFF Research Database (Denmark)

    Poulsen, Mads Hvid; Nielsen, Morten Frost Munk; Abrahamsen, Bo

    2014-01-01

    Abstract Objective. The aim of this study was to analyse the prevalence of osteoporosis and risk factors of osteoporotic fractures before androgen deprivation in Danish men. Treatment and prognosis of prostate cancer necessitate management of long-term consequences of androgen deprivation therapy...... (ADT), including accelerated bone loss resulting in osteoporosis. Osteoporotic fractures are associated with excess morbidity and mortality. Material and methods. Patients with prostate cancer awaiting initiation of ADT were consecutively included. Half of the patients had localized disease and were...... level was 30.5 g/l (1-5714 g/l). The average Gleason score was 7.8 (range 5-10, SD 1.1). Fifty patients had localized prostate cancer and the other 55 patients had disseminated disease. The prevalence of osteoporosis was 10% and the prevalence of osteopenia was 58% before ADT. There was no significant...

  19. The incidence and mortality of prostate cancer and its relationship with development in Asia.

    Science.gov (United States)

    Pakzad, Reza; Mohammadian-Hafshejani, Abdollah; Ghoncheh, Mahshid; Pakzad, Iraj; Salehiniya, Hamid

    2015-12-01

    Prostate cancer is a common cancer in men in the world. It is rapidly increasing. This study investigated the incidence and mortality of prostate cancer and the relationship with the Human Development Index (HDI) and its dimensions in Asia in 2012. The study was conducted based on data from the world data of cancer and the World Bank (including the HDI and its components). The standardized incidence and mortality rates of prostate cancer were calculated for Asian countries. The correlation between incidence, mortality rates, and the HDI and its components were assessed with the use of the correlation test, using SPSS software. There was a total of 191,054 incidences and 81,229 death were recorded in Asian countries in 2012. Among the Asian countries, the five countries with the highest standardized incidence rates of prostate cancer were Israel, Turkey, Lebanon, Singapore, and Japan, and the five countries with the highest standardized mortality rates were Turkey, Lebanon, Timor-Leste, Armenia, and the Philippines. The correlation between standardized incidence rate of prostate cancer and the HDI was 0.604 (P ≤ 0.001), with life expectancy at birth 0.529 (P = 0.002), with mean years of schooling 0.427 (P = 0.001), and with level of income per each person of the population 0.349 (P = 0.013). Also, between the standardized mortality rate and the HDI, it was 0.228 (P = 0.127). A significant and positive correlation was observed between the standardized incidence rate of prostate cancer, and the HDI and its dimensions, such as life expectancy at birth, mean years of schooling, and income level of the population per each person of population. However, there was no significant correlation between the standardized mortality rate, and the HDI and its dimensions.

  20. The NLR-related protein NWD1 is associated with prostate cancer and modulates androgen receptor signaling.

    Science.gov (United States)

    Correa, Ricardo G; Krajewska, Maryla; Ware, Carl F; Gerlic, Motti; Reed, John C

    2014-03-30

    Prostate cancer (PCa) is among the leading causes of cancer-related death in men. Androgen receptor (AR) signaling plays a seminal role in prostate development and homeostasis, and dysregulation of this pathway is intimately linked to prostate cancer pathogenesis and progression. Here, we identify the cytosolic NLR-related protein NWD1 as a novel modulator of AR signaling. We determined that expression of NWD1 becomes elevated during prostate cancer progression, based on analysis of primary tumor specimens. Experiments with cultured cells showed that NWD1 expression is up-regulated by the sex-determining region Y (SRY) family proteins. Gene silencing procedures, in conjunction with transcriptional profiling, showed that NWD1 is required for expression of PDEF (prostate-derived Ets factor), which is known to bind and co-regulate AR. Of note, NWD1 modulates AR protein levels. Depleting NWD1 in PCa cell lines reduces AR levels and suppresses activity of androgen-driven reporter genes. NWD1 knockdown potently suppressed growth of androgen-dependent LNCaP prostate cancer cells, thus showing its functional importance in an AR-dependent tumor cell model. Proteomic analysis suggested that NWD1 associates with various molecular chaperones commonly related to AR complexes. Altogether, these data suggest a role for tumor-associated over-expression of NWD1 in dysregulation of AR signaling in PCa.

  1. Epigenome-Wide Tumor DNA Methylation Profiling Identifies Novel Prognostic Biomarkers of Metastatic-Lethal Progression in Men Diagnosed with Clinically Localized Prostate Cancer.

    Science.gov (United States)

    Zhao, Shanshan; Geybels, Milan S; Leonardson, Amy; Rubicz, Rohina; Kolb, Suzanne; Yan, Qingxiang; Klotzle, Brandy; Bibikova, Marina; Hurtado-Coll, Antonio; Troyer, Dean; Lance, Raymond; Lin, Daniel W; Wright, Jonathan L; Ostrander, Elaine A; Fan, Jian-Bing; Feng, Ziding; Stanford, Janet L

    2017-01-01

    Aside from Gleason sum, few factors accurately identify the subset of prostate cancer patients at high risk for metastatic progression. We hypothesized that epigenetic alterations could distinguish prostate tumors with life-threatening potential. Epigenome-wide DNA methylation profiling was performed in surgically resected primary tumor tissues from a population-based (n = 430) and a replication (n = 80) cohort of prostate cancer patients followed prospectively for at least 5 years. Metastasis was confirmed by positive bone scan, MRI, CT, or biopsy, and death certificates confirmed cause of death. AUC, partial AUC (pAUC, 95% specificity), and P value criteria were used to select differentially methylated CpG sites that robustly stratify patients with metastatic-lethal from nonrecurrent tumors, and which were complementary to Gleason sum. Forty-two CpG biomarkers stratified patients with metastatic-lethal versus nonrecurrent prostate cancer in the discovery cohort, and eight of these CpGs replicated in the validation cohort based on a significant (P prostate cancer include CpGs in five genes (ALKBH5, ATP11A, FHAD1, KLHL8, and PI15) and three intergenic regions. In the validation dataset, the AUC for Gleason sum alone (0.82) significantly increased with the addition of four individual CpGs (range, 0.86-0.89; all P epigenetic biomarkers warrant further investigation as they may improve prognostic classification of patients with clinically localized prostate cancer and provide new insights on tumor aggressiveness. Clin Cancer Res; 23(1); 311-9. ©2016 AACR. ©2016 American Association for Cancer Research.

  2. Defective DNA repair mechanisms in prostate cancer: impact of olaparib

    Directory of Open Access Journals (Sweden)

    De Felice F

    2017-03-01

    Full Text Available Francesca De Felice,1 Vincenzo Tombolini,1 Francesco Marampon,2 Angela Musella,3 Claudia Marchetti3 1Department of Radiotherapy, Policlinico Umberto I, “Sapienza” University of Rome, Rome, 2Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L’Aquila, L’Aquila, 3Department of Gynecological and Obstetrical Sciences and Urological Sciences, “Sapienza” University of Rome, Rome, Italy Abstract: The field of prostate oncology has continued to change dramatically. It has truly become a field that is intensely linked to molecular genetic alterations, especially DNA-repair defects. Germline breast cancer 1 gene (BRCA1 and breast cancer 2 gene (BRCA2 mutations are implicated in the highest risk of prostate cancer (PC predisposition and aggressiveness. Poly adenosine diphosphate ribose polymerase (PARP proteins play a key role in DNA repair mechanisms and represent a valid target for new therapies. Olaparib is an oral PARP inhibitor that blocks DNA repair pathway and coupled with BRCA mutated-disease results in tumor cell death. In phase II clinical trials, including patients with advanced castration-resistant PC, olaparib seems to be efficacious and well tolerated. Waiting for randomized phase III trials, olaparib should be considered as a promising treatment option for PC. Keywords: prostate cancer, metastatic disease, castration resistant, BRCA, DNA-repair, PARP, olaparib

  3. Prostate Cancer Probability Prediction By Machine Learning Technique.

    Science.gov (United States)

    Jović, Srđan; Miljković, Milica; Ivanović, Miljan; Šaranović, Milena; Arsić, Milena

    2017-11-26

    The main goal of the study was to explore possibility of prostate cancer prediction by machine learning techniques. In order to improve the survival probability of the prostate cancer patients it is essential to make suitable prediction models of the prostate cancer. If one make relevant prediction of the prostate cancer it is easy to create suitable treatment based on the prediction results. Machine learning techniques are the most common techniques for the creation of the predictive models. Therefore in this study several machine techniques were applied and compared. The obtained results were analyzed and discussed. It was concluded that the machine learning techniques could be used for the relevant prediction of prostate cancer.

  4. Multidisciplinary Intervention of Early, Lethal Metastatic Prostate Cancer: Report From the 2015 Coffey-Holden Prostate Cancer Academy Meeting

    Science.gov (United States)

    Miyahira, Andrea K.; Lang, Joshua M.; Den, Robert B.; Garraway, Isla P.; Lotan, Tamara L.; Ross, Ashley E.; Stoyanova, Tanya; Cho, Steve Y.; Simons, Jonathan W.; Pienta, Kenneth J.; Soule, Howard R.

    2018-01-01

    BACKGROUND The 2015 Coffey-Holden Prostate Cancer Academy Meeting, themed: “Multidisciplinary Intervention of Early, Lethal Metastatic Prostate Cancer,” was held in La Jolla, California from June 25 to 28, 2015. METHODS The Prostate Cancer Foundation (PCF) sponsors an annual, invitation-only, action-tank-structured meeting on a critical topic concerning lethal prostate cancer. The 2015 meeting was attended by 71 basic, translational, and clinical investigators who discussed the current state of the field, major unmet needs, and ideas for addressing earlier diagnosis and treatment of men with lethal prostate cancer for the purpose of extending lives and making progress toward a cure. RESULTS The questions addressed at the meeting included: cellular and molecular mechanisms of tumorigenesis, evaluating, and targeting the microenvironment in the primary tumor, advancing biomarkers for clinical integration, new molecular imaging technologies, clinical trials, and clinical trial design in localized high-risk and oligometastatic settings, targeting the primary tumor in advanced disease, and instituting multi-modal care of high risk and oligometastatic patients. DISCUSSION This article highlights the current status, greatest unmet needs, and anticipated field changes that were discussed at the meeting toward the goal of optimizing earlier interventions to potentiate cures in high-risk and oligometastatic prostate cancer patients. PMID:26477609

  5. Alcohol consumption and prostate cancer incidence and progression

    DEFF Research Database (Denmark)

    Brunner, Clair; Davies, Neil M; Martin, Richard M

    2017-01-01

    Prostate cancer is the most common cancer in men in developed countries, and is a target for risk reduction strategies. The effects of alcohol consumption on prostate cancer incidence and survival remain unclear, potentially due to methodological limitations of observational studies. In this stud...... consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression....

  6. Influence of the neural microenvironment on prostate cancer.

    Science.gov (United States)

    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.

  7. PSA, PSA derivatives, proPSA and prostate health index in the diagnosis of prostate cancer

    OpenAIRE

    Ayyıldız, Sema Nur; Ayyıldız, Ali

    2014-01-01

    Currently, prostate- specific antigen (PSA) is the most common oncological marker used for prostate cancer screening. However, high levels of PSA in benign prostatic hyperplasia and prostatitis decrease the specificity of PSA as a cancer marker. To increase the specificity of PSA, PSA derivatives and PSA kinetics have been used. However, these new techniques were not able to increase the diagnostic specificity for prostate cancer. Therefore, the search for new molecules and derivatives of PSA...

  8. Risk of prostate and bladder cancers in patients with spinal cord injury: a population-based cohort study.

    Science.gov (United States)

    Lee, Wen-Yuan; Sun, Li-Min; Lin, Cheng-Li; Liang, Ji-An; Chang, Yen-Jung; Sung, Fung-Chang; Kao, Chia-Hung

    2014-01-01

    To evaluate the risk of prostate and bladder cancers in patients with spinal cord injury (SCI). We used data obtained from the National Health Insurance system of Taiwan for this study. The SCI cohort contained 54,401 patients with SCI, and each patient was randomly frequency matched with 4 people from the general population (without SCI) based on age, sex, and index date. Incidence rates, SCI cohort to non-SCI cohort rate ratios, and hazard ratios were measured to evaluate the cancer risks. Patients with SCI showed a significantly lower risk of developing prostate cancer compared with subjects without SCI (adjusted hazard ratio = 0.73; 95% confidence interval = 0.59, 0.90), after accounting for the competing risk of death. No significant difference in the risk of bladder cancer emerged between the SCI and control groups. Further analyses found a higher spinal level of SCI tended to predict a lower risk for prostate cancer. Patients with SCI incurred a lower risk for prostate cancer compared with people without SCI. The risk for bladder cancer did not differ between people with or without SCI. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. [Radiotherapy in node-positive prostate cancer].

    Science.gov (United States)

    Bottke, D; Bartkowiak, D; Bolenz, C; Wiegel, T

    2016-03-01

    There are numerous randomized trials to guide the management of patients with localized (and metastatic) prostate cancer, but only a few (mostly retrospective) studies have specifically addressed node-positive patients. Therefore, there is uncertainty regarding optimal treatment in this situation. Current guidelines recommend long-term androgen deprivation therapy (ADT) alone or radiotherapy plus long-term ADT as treatment options. This overview summarizes the existing literature on the use of radiotherapy for node-positive prostate cancer as definitive treatment and as adjuvant or salvage therapy after radical prostatectomy. In this context, we also discuss several PET tracers in the imaging evaluation of patients with biochemical recurrence of prostate cancer after radical prostatectomy. As for definitive treatment, retrospective studies suggest that ADT plus radiotherapy improves overall survival compared with ADT alone. These studies also consistently demonstrated that many patients with node-positive prostate cancer can achieve long-term survival - and are likely curable - with aggressive therapy. The beneficial impact of adjuvant radiotherapy on survival in patients with pN1 prostate cancer seems to be highly influenced by tumor characteristics. Men with ≤ 2 positive lymph nodes in the presence of intermediate- to high-grade disease, or positive margins, and those with 3 or 4 positive lymph nodes are the ideal candidates for adjuvant radiotherapy (plus long-term ADT) after surgery. There is a need for randomized trials to further examine the potential role of radiotherapy as either definitive or adjuvant treatment, for patients with node-positive prostate cancer.

  10. Optimizing structural and mechanical properties of cryogel scaffolds for use in prostate cancer cell culturing

    International Nuclear Information System (INIS)

    Cecilia, A.; Baecker, A.; Hamann, E.; Rack, A.; Kamp, T. van de; Gruhl, F.J.; Hofmann, R.; Moosmann, J.; Hahn, S.; Kashef, J.; Bauer, S.; Farago, T.; Helfen, L.

    2017-01-01

    Prostate cancer (PCa) currently is the second most diagnosed cancer in men and the second most cause of cancer death after lung cancer in Western societies. This sets the necessity of modelling prostatic disorders to optimize a therapy against them. The conventional approach to investigating prostatic diseases is based on two-dimensional (2D) cell culturing. This method, however, does not provide a three-dimensional (3D) environment, therefore impeding a satisfying simulation of the prostate gland in which the PCa cells proliferate. Cryogel scaffolds represent a valid alternative to 2D culturing systems for studying the normal and pathological behavior of the prostate cells thanks to their 3D pore architecture that reflects more closely the physiological environment in which PCa cells develop. In this work the 3D morphology of three potential scaffolds for PCa cell culturing was investigated by means of synchrotron X-ray computed micro tomography (SXCμT) fitting the according requirements of high spatial resolution, 3D imaging capability and low dose requirements very well. In combination with mechanical tests, the results allowed identifying an optimal cryogel architecture, meeting the needs for a well-suited scaffold to be used for 3D PCa cell culture applications. The selected cryogel was then used for culturing prostatic lymph node metastasis (LNCaP) cells and subsequently, the presence of multi-cellular tumor spheroids inside the matrix was demonstrated again by using SXCμT. - Highlights: • Synthesis of cryogel scaffolds for prostate cancer cell culturing. • Study of cryogel morphology by synchrotron X-ray computed micro tomography. • Analysis of cryogel mechanical properties with laboratory techniques. • Culturing of prostate cancer cell in the optimal cryogel composition for 21 days. • 3D visualization of the cells by synchrotron X-ray computed micro tomography.

  11. Optimizing structural and mechanical properties of cryogel scaffolds for use in prostate cancer cell culturing

    Energy Technology Data Exchange (ETDEWEB)

    Cecilia, A. [Institute for Photon Science and Synchrotron Radiation (IPS), Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen (Germany); Baecker, A. [Institute of Microstructure Technology (IMT), Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1 Bldg 329, Eggenstein-Leopoldshafen, Karlsruhe D-76344 (Germany); Hamann, E. [Institute for Photon Science and Synchrotron Radiation (IPS), Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen (Germany); Rack, A. [European Synchrotron Radiation Facility (ESRF), 6 rue Jules Horowitz, 38000 Grenoble (France); Kamp, T. van de [Laboratory for Applications of Synchrotron Radiation (LAS), Karlsruhe Institute of Technology, 6980, D-76128 Karlsruhe (Germany); Gruhl, F.J. [Institute of Microstructure Technology (IMT), Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1 Bldg 329, Eggenstein-Leopoldshafen, Karlsruhe D-76344 (Germany); Hofmann, R. [Institute for Photon Science and Synchrotron Radiation (IPS), Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen (Germany); Moosmann, J. [Institute of Materials Research, Helmholtz-Zentrum Geesthacht (HZG), Max-Planck-Str. 1, D-21502 Geesthacht (Germany); Hahn, S.; Kashef, J.; Bauer, S.; Farago, T. [Institute for Photon Science and Synchrotron Radiation (IPS), Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen (Germany); Helfen, L. [Institute for Photon Science and Synchrotron Radiation (IPS), Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen (Germany); European Synchrotron Radiation Facility (ESRF), 6 rue Jules Horowitz, 38000 Grenoble (France); and others

    2017-02-01

    Prostate cancer (PCa) currently is the second most diagnosed cancer in men and the second most cause of cancer death after lung cancer in Western societies. This sets the necessity of modelling prostatic disorders to optimize a therapy against them. The conventional approach to investigating prostatic diseases is based on two-dimensional (2D) cell culturing. This method, however, does not provide a three-dimensional (3D) environment, therefore impeding a satisfying simulation of the prostate gland in which the PCa cells proliferate. Cryogel scaffolds represent a valid alternative to 2D culturing systems for studying the normal and pathological behavior of the prostate cells thanks to their 3D pore architecture that reflects more closely the physiological environment in which PCa cells develop. In this work the 3D morphology of three potential scaffolds for PCa cell culturing was investigated by means of synchrotron X-ray computed micro tomography (SXCμT) fitting the according requirements of high spatial resolution, 3D imaging capability and low dose requirements very well. In combination with mechanical tests, the results allowed identifying an optimal cryogel architecture, meeting the needs for a well-suited scaffold to be used for 3D PCa cell culture applications. The selected cryogel was then used for culturing prostatic lymph node metastasis (LNCaP) cells and subsequently, the presence of multi-cellular tumor spheroids inside the matrix was demonstrated again by using SXCμT. - Highlights: • Synthesis of cryogel scaffolds for prostate cancer cell culturing. • Study of cryogel morphology by synchrotron X-ray computed micro tomography. • Analysis of cryogel mechanical properties with laboratory techniques. • Culturing of prostate cancer cell in the optimal cryogel composition for 21 days. • 3D visualization of the cells by synchrotron X-ray computed micro tomography.

  12. Commentary on "identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array." COGS-Cancer Research UK GWAS-ELLIPSE (part of GAME-ON) Initiative; Australian Prostate Cancer Bioresource; UK Genetic Prostate Cancer Study Collaborators/British Association

    DEFF Research Database (Denmark)

    Olumi, Aria F; Nordestgaard, Børge G.

    2014-01-01

    Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the internationa...

  13. Validation and application of a death proxy in adult cancer patients.

    Science.gov (United States)

    Mealing, Nicole M; Dobbins, Timothy A; Pearson, Sallie-Anne

    2012-07-01

    PURPOSE: Fact of death is not always available on data sets used for pharmacoepidemiological research. Proxies may be an appropriate substitute in the absence of death data. The purposes of this study were to validate a proxy for death in adult cancer patients and to assess its performance when estimating survival in two cohorts of cancer patients. METHODS: We evaluated 30-, 60-, 90- and 180-day proxies overall and by cancer type using data from 12 394 Australian veterans with lung, colorectal, breast or prostate cancer. The proxy indicated death if the difference between the last dispensing record and the end of the observational period exceeded the proxy cutoff. We then compared actual survival to 90-day proxy estimates in a subset of 4090 veterans with 'full entitlements' for pharmaceutical items and in 3704 Australian women receiving trastuzumab for HER2+ metastatic breast cancer. RESULTS: The 90-day proxy was optimal with an overall sensitivity of 99.3% (95%CI: 98.4-99.7) and a specificity of 97.6% (95%CI: 91.8-99.4). These measures remained high when evaluated by cancer type and spread of disease. The application of the proxy using the most conservative date of death estimate (date of last dispensing) generally underestimated survival, with estimates up to 3 months shorter than survival based on fact of death. CONCLUSIONS: A 90-day death proxy is a robust substitute to identify death in a chronic population when fact of death is not available. The proxy is likely to be valid across a range of chronic diseases as it relies on the presence of 'regular' dispensing records for individual patients. Copyright © 2011 John Wiley & Sons, Ltd. Copyright © 2011 John Wiley & Sons, Ltd.

  14. Curcumin analog WZ35 induced cell death via ROS-dependent ER stress and G2/M cell cycle arrest in human prostate cancer cells

    International Nuclear Information System (INIS)

    Zhang, Xiuhua; Chen, Minxiao; Zou, Peng; Kanchana, Karvannan; Weng, Qiaoyou; Chen, Wenbo; Zhong, Peng; Ji, Jiansong; Zhou, Huiping; He, Langchong; Liang, Guang

    2015-01-01

    Prostate cancer is the most commonly diagnosed malignancy among men. The Discovery of new agents for the treatment of prostate cancer is urgently needed. Compound WZ35, a novel analog of the natural product curcumin, exhibited good anti-prostate cancer activity, with an IC 50 of 2.2 μM in PC-3 cells. However, the underlying mechanism of WZ35 against prostate cancer cells is still unclear. Human prostate cancer PC-3 cells and DU145 cells were treated with WZ35 for further proliferation, apoptosis, cell cycle, and mechanism analyses. NAC and CHOP siRNA were used to validate the role of ROS and ER stress, respectively, in the anti-cancer actions of WZ35. Our results show that WZ35 exhibited much higher cell growth inhibition than curcumin by inducing ER stress-dependent cell apoptosis in human prostate cells. The reduction of CHOP expression by siRNA partially abrogated WZ35-induced cell apoptosis. WZ35 also dose-dependently induced cell cycle arrest in the G2/M phase. Furthermore, we found that WZ35 treatment for 30 min significantly induced reactive oxygen species (ROS) production in PC-3 cells. Co-treatment with the ROS scavenger NAC completely abrogated the induction of WZ35 on cell apoptosis, ER stress activation, and cell cycle arrest, indicating an upstream role of ROS generation in mediating the anti-cancer effect of WZ35. Taken together, this work presents the novel anticancer candidate WZ35 for the treatment of prostate cancer, and importantly, reveals that increased ROS generation might be an effective strategy in human prostate cancer treatment. The online version of this article (doi:10.1186/s12885-015-1851-3) contains supplementary material, which is available to authorized users

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

    Science.gov (United States)

    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.

  16. Fatherhood and incident prostate cancer in a prospective US cohort.

    Science.gov (United States)

    Eisenberg, Michael L; Park, Yikyung; Brinton, Louise A; Hollenbeck, Albert R; Schatzkin, Arthur

    2011-04-01

    Fatherhood status has been hypothesized to affect prostate cancer risk but the current evidence is limited and contradictory. We prospectively evaluated the relationship between offspring number and the risk of prostate cancer in 161,823 men enrolled in the National Institues of Health - American Association of Retired Persons Diet and Health Study. Participants were aged 50-71 years without a cancer diagnosis at baseline in 1995. Analysing 8134 cases of prostate cancer, Cox regression was used to estimate the association between offspring number and prostate cancer incidence while accounting for socio-demographic and lifestyle characteristics. When examining the entire cohort, there was no relationship between fatherhood and incident prostate cancer [hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.86-1.02]. However, after stratifying for prostate cancer screening, prostate-specific antigen (PSA) unscreened childless men had a lower risk of prostate cancer (HR 0.73, 95% CI 0.58-0.91) compared with fathers due to the interaction between PSA screening and fatherhood (P for interaction fatherhood status and offspring gender is associated with a man's prostate cancer risk.

  17. Src: marker or actor of prostate cancer aggressiveness

    Directory of Open Access Journals (Sweden)

    Virginie eVlaeminck-Guillem

    2014-08-01

    Full Text Available A key question for urologic practitioners is whether an apparently organ-confined prostate cancer is actually aggressive or not. The dilemma is to specifically identify among all prostate tumors the very aggressive high-grade cancers that will become life-threatening by developing extra-prostatic invasion and metastatic potential and the indolent cancers that will never modify a patient’s life expectancy. A choice must be made between several therapeutic options to achieve the optimal personalized management of the disease that causes as little harm as possible to patients. Reliable clinical, biological or pathological markers that would enable distinctions to be made between aggressive and indolen prostate cancers in routine practice at the time of initial diagnosis are still lacking. The molecular mechanisms that explain why a prostate cancer is aggressive or not are also poorly understood. Among the potential markers and/or actors in prostate cancer aggressiveness, Src and other members of the Src kinase family, are valuable candidates. Activation of Src-dependent intracellular pathways is frequently observed in prostate cancer. Indeed, Src is at the cross-roads of several pathways (including androgen receptor, TGFbeta, Bcl-2, Akt/PTEN or MAPK and ERK …, and is now known to influence some of the cellular and tissular events that accompany tumor progression: cell proliferation, cell motility, invasion, epithelial-to-mesenchymal transition, resistance to apoptosis, angiogenesis, neuroendocrine differentiation, and metastatic spread. Recent work even suggests that Src could also play a part in prostate cancer initiation in coordination with the androgen receptor. The aim of this review is to gather data that explores the links between the Src kinase family and prostate cancer progression and aggressiveness.

  18. The Role of Prostatitis in Prostate Cancer: Meta-Analysis

    Science.gov (United States)

    Yunxia, Zhang; Zhu, Hong; Liu, Junjiang; Pumill, Chris

    2013-01-01

    Objective Use systematic review methods to quantify the association between prostatitis and prostate cancer, under both fixed and random effects model. Evidence Acquisition Case control studies of prostate cancer with information on prostatitis history. All studies published between 1990-2012, were collected to calculate a pooled odds ratio. Selection criteria: the selection criteria are as follows: human case control studies; published from May 1990 to July 2012; containing number of prostatitis, and prostate cancer cases. Evidence Synthesis In total, 20 case control studies were included. A significant association between prostatitis and prostate cancer was found, under both fixed effect model (pooled OR=1.50, 95%CI: 1.39-1.62), and random effects model (OR=1.64, 95%CI: 1.36-1.98). Personal interview based case control studies showed a high level of association (fixed effect model: pooled OR=1.59, 95%CI: 1.47-1.73, random effects model: pooled OR= 1.87, 95%CI: 1.52-2.29), compared with clinical based studies (fixed effect model: pooled OR=1.05, 95%CI: 0.86-1.28, random effects model: pooled OR= 0.98, 95%CI: 0.67-1.45). Additionally, pooled ORs, were calculated for each decade. In a fixed effect model: 1990’s: OR=1.58, 95% CI: 1.35-1.84; 2000’s: OR=1.59, 95% CI: 1.40-1.79; 2010’s: OR=1.37, 95% CI: 1.22-1.56. In a random effects model: 1990’s: OR=1.98, 95% CI: 1.08-3.62; 2000’s: OR=1.64, 95% CI: 1.23-2.19; 2010’s: OR=1.34, 95% CI: 1.03-1.73. Finally a meta-analysis stratified by each country was conducted. In fixed effect models, U.S: pooled OR =1.45, 95%CI: 1.34-1.57; China: pooled OR =4.67, 95%CI: 3.08-7.07; Cuba: pooled OR =1.43, 95%CI: 1.00-2.04; Italy: pooled OR =0.61, 95%CI: 0.13-2.90. In random effects model, U.S: pooled OR=1.50, 95%CI: 1.25-1.80; China: pooled OR =4.67, 95%CI: 3.08-7.07; Cuba: pooled OR =1.43, 95%CI: 1.00-2.04; Italy: pooled OR =0.61, 95%CI: 0.13-2.90.CONCLUSIONS: the present meta-analysis provides the statistical evidence that

  19. Combination therapy with hormonal, radiation and chemotherapy for stage C prostate cancer

    International Nuclear Information System (INIS)

    Iwasawa, Toshihisa; Matsumoto, Hidetsugu

    1996-01-01

    To improve the effectiveness of treatment for patients with stage C prostate cancer, therapy in combination with hormonal, radiation and chemotherapy was given for the initial period, and there after, hormonal therapy was continuously administered to 18 patients with chemotherapy and three patients without it. At the Social Health Insurance Medical Center, between May 1988 and August 1991, 21 patients were diagnosed to have stage C histologically confirmed adenocarcinoma of the prostate. The average age of the patients was 69.0 years. The tumor was well, moderate and poorly differentiated in 5, 6 and 10 patients, respectively. As hormonal therapy, orchiectomy was performed on 19 of the 21 patients. Furthermore, 11 patients were administered estramustine phosphate, 9 chlormadinone acetate, and one diethylstilbesterol diphosphate. As, radiation therapy, all patients were treated with AP-PA parallel opposing technique to small pelvis with a 12 cm x 12 cm treatment field (44-45 Gy) combined with conformation radiotherapy to prostate (20-26 Gy). Chemotherapy was performed using either one or a combination of the following; cis-diamminedichloroplatinum, adriamycin, cyclophosphamide, 5-fluorouracil, methotrexate and etoposide. The observation period was 54.5 months on the average. Recurrence was observed in 3 patients, for all of which the sites were at bone. The 5-year non-recurrence rate was 90.4% by Kaplan-Meier's method. There were 4 deaths, three were due to prostate cancer and one to gastric cancer. The 5-year cumulative survival rate by Kaplan-Meier's method was 90.5%. In conclusion, this treatment was effective for stage C cases of prostate cancer. (author)

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

    Science.gov (United States)

    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 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.

  1. Immune-Stimulating Combinatorial Therapy for Prostate Cancer

    Science.gov (United States)

    2016-10-01

    Overlap: None 20 90061946 (Drake) Title: Epigenetic Drugs and Immuno Therapy for Prostate Cancer (EDIT-PC) Effort: 1.2 calendar months (10% effort...AWARD NUMBER: W81XWH-15-1-0667 TITLE: Immune-Stimulating Combinatorial Therapy for Prostate Cancer PRINCIPAL INVESTIGATOR: Robert Ivkov...Stimulating Combinatorial Therapy for Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0667 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

  2. Diet and prostate cancer - a holistic approach to management.

    Science.gov (United States)

    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.

  3. Screening for prostate cancer with the prostate-specific antigen test: are patients making informed decisions?

    Science.gov (United States)

    O'Dell, K J; Volk, R J; Cass, A R; Spann, S J

    1999-09-01

    The benefits of early detection of prostate cancer are uncertain, and the American College of Physicians and the American Academy of Family Physicians recommend individual decision making in prostate cancer screening. This study reports the knowledge of male primary care patients about prostate cancer and prostate-specific antigen (PSA) testing and examines how that knowledge is related to PSA testing, preferences for testing in the future, and desire for involvement in physician-patient decision making. The sample included 160 men aged 45 to 70 years with no history of prostate cancer who presented for care at a university-based family medicine clinic. Before scheduled office visits, patients completed a questionnaire developed for this study that included a 10-question measure of prostate cancer knowledge, the Deber-Kraestchmer Problem-Solving Decision-Making Scale, sociodemographic indicators, and questions on PSA testing. In general, patients who were college graduates were more knowledgeable about prostate cancer and early detection than those with a high school education or less. Aside from college graduates, most patients could not identify the principle advantages and disadvantages of PSA testing. Patients indicating previous or future plans for PSA testing demonstrated greater knowledge than other patients. Desire for involvement in decision making varied by patient education but was not related to past PSA testing. Patients lack knowledge about prostate cancer and early detection. This knowledge deficit may impede the early detection of prostate cancer and is a barrier to making an informed decision about undergoing PSA testing.

  4. Sildenafil (Viagra) sensitizes prostate cancer cells to doxorubicin-mediated apoptosis through CD95

    Science.gov (United States)

    Das, Anindita; Durrant, David; Mitchell, Clint; Dent, Paul; Batra, Surinder K.; Kukreja, Rakesh C.

    2016-01-01

    We previously reported that Sildenafil enhances apoptosis and antitumor efficacy of doxorubicin (DOX) while attenuating its cardiotoxic effect in prostate cancer. In the present study, we investigated the mechanism by which sildenafil sensitizes DOX in killing of prostate cancer (PCa) cells, DU145. The death receptor Fas (APO-1 or CD95) induces apoptosis in many carcinoma cells, which is negatively regulated by anti-apoptotic molecules such as FLIP (Fas-associated death domain (FADD) interleukin-1-converting enzyme (FLICE)-like inhibitory protein). Co-treatment of PCa cells with sildenafil and DOX for 48 hours showed reduced expression of both long and short forms of FLIP (FLIP-L and -S) as compared to individual drug treatment. Over-expression of FLIP-s with an adenoviral vector attentuated the enhanced cell-killing effect of DOX and sildenafil. Colony formation assays also confirmed that FLIP-S over-expression inhibited the DOX and sildenafil-induced synergistic killing effect as compared to the cells infected with an empty vector. Moreover, siRNA knock-down of CD95 abolished the effect of sildenafil in enhancing DOX lethality in cells, but had no effect on cell killing after treatment with a single agent. Sildenafil co-treatment with DOX inhibited DOX-induced NF-κB activity by reducing phosphorylation of IκB and nuclear translocation of the p65 subunit, in addition to down regulation of FAP-1 (Fas associated phosphatase-1, a known inhibitor of CD95-mediated apoptosis) expression. This data provides evidence that the CD95 is a key regulator of sildenafil and DOX mediated enhanced cell death in prostate cancer. PMID:26716643

  5. The integrated proactive surveillance system for prostate cancer.

    Science.gov (United States)

    Wang, Haibin; Yatawara, Mahendra; Huang, Shao-Chi; Dudley, Kevin; Szekely, Christine; Holden, Stuart; Piantadosi, Steven

    2012-01-01

    In this paper, we present the design and implementation of the integrated proactive surveillance system for prostate cancer (PASS-PC). The integrated PASS-PC is a multi-institutional web-based system aimed at collecting a variety of data on prostate cancer patients in a standardized and efficient way. The integrated PASS-PC was commissioned by the Prostate Cancer Foundation (PCF) and built through the joint of efforts by a group of experts in medical oncology, genetics, pathology, nutrition, and cancer research informatics. Their main goal is facilitating the efficient and uniform collection of critical demographic, lifestyle, nutritional, dietary and clinical information to be used in developing new strategies in diagnosing, preventing and treating prostate cancer.The integrated PASS-PC is designed based on common industry standards - a three tiered architecture and a Service- Oriented Architecture (SOA). It utilizes open source software and programming languages such as HTML, PHP, CSS, JQuery, Drupal and MySQL. We also use a commercial database management system - Oracle 11g. The integrated PASS-PC project uses a "confederation model" that encourages participation of any interested center, irrespective of its size or location. The integrated PASS-PC utilizes a standardized approach to data collection and reporting, and uses extensive validation procedures to prevent entering erroneous data. The integrated PASS-PC controlled vocabulary is harmonized with the National Cancer Institute (NCI) Thesaurus. Currently, two cancer centers in the USA are participating in the integrated PASS-PC project.THE FINAL SYSTEM HAS THREE MAIN COMPONENTS: 1. National Prostate Surveillance Network (NPSN) website; 2. NPSN myConnect portal; 3. Proactive Surveillance System for Prostate Cancer (PASS-PC). PASS-PC is a cancer Biomedical Informatics Grid (caBIG) compatible product. The integrated PASS-PC provides a foundation for collaborative prostate cancer research. It has been built to

  6. XMRV Discovery and Prostate Cancer-Related Research

    Directory of Open Access Journals (Sweden)

    David E. Kang

    2011-01-01

    Full Text Available Xenotropic murine leukemia virus-related virus (XMRV was first reported in 2006 in a study of human prostate cancer patients with genetic variants of the antiviral enzyme, RNase L. Subsequent investigations in North America, Europe, Asia, and Africa have either observed or failed to detect XMRV in patients (prostate cancer, chronic fatigue syndrome-myalgic encephalomyelitis (CFS-ME, and immunosuppressed with respiratory tract infections or normal, healthy, control individuals. The principal confounding factors are the near ubiquitous presence of mouse-derived reagents, antibodies and cells, and often XMRV itself, in laboratories. XMRV infects and replicates well in many human cell lines, but especially in certain prostate cancer cell lines. XMRV also traffics to prostate in a nonhuman primate model of infection. Here, we will review the discovery of XMRV and then focus on prostate cancer-related research involving this intriguing virus.

  7. Combined androgen blockade in the treatment of advanced prostate cancer--an overview. The Scandinavian Prostatic Cancer Group

    DEFF Research Database (Denmark)

    Iversen, P

    1997-01-01

    The value of combined androgen blockade in the treatment of patients with advanced prostate cancer is still controversial. In this review by the Scandinavian Prostatic Cancer Group, the literature addressing the concept and its clinical use is critically reviewed....

  8. Attachment of a Genetically Engineered Antibody to a Carbon Nanotube Transistor for Detection of Prostate Cancer Biomarkers

    Science.gov (United States)

    Lerner, Mitchell; Dailey, Jennifer; Goldsmith, Brett; Robinson, Matthew; Johnson, A. T. Charlie

    2011-03-01

    We have developed a novel detection method for osteopontin (OPN) by attaching an engineered single chain variable fragment (scFv) protein with high binding affinity for OPN to a carbon nanotube transistor. Osteopontin is a potential new biomarker for prostate cancer; its presence in humans is already associated with several forms of cancer, arthritis, osteoporosis and stress. Prostate cancer is the most commonly diagnosed cancer and second leading cause of cancer deaths among American men and as such represents a major public health issue. Detection of early-stage cancer often results in successful treatment, with long term disease-free survival in 60-90% of patients. Electronic transport measurements are used to detect the presence of OPN in solution at clinically relevant concentrations.

  9. Beyond the androgen receptor II: New approaches to understanding and treating metastatic prostate cancer; Report from the 2017 Coffey-Holden Prostate Cancer Academy Meeting.

    Science.gov (United States)

    Miyahira, Andrea K; Cheng, Heather H; Abida, Wassim; Ellis, Leigh; Harshman, Lauren C; Spratt, Daniel E; Simons, Jonathan W; Pienta, Kenneth J; Soule, Howard R

    2017-11-01

    The 2017 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Beyond the Androgen Receptor II: New Approaches to Understanding and Treating Metastatic Prostate Cancer," was held in Carlsbad, California from June 14-17, 2017. The CHPCA is an annual scientific conference hosted by the Prostate Cancer Foundation (PCF) that is uniquely designed to produce extensive and constructive discussions on the most urgent and impactful topics concerning research into the biology and treatment of metastatic prostate cancer. The 2017 CHPCA Meeting was the 5th meeting in this annual series and was attended by 71 investigators focused on prostate cancer and a variety of other fields including breast and ovarian cancer. The discussions at the meeting were concentrated on topics areas including: mechanisms and therapeutic approaches for molecular subclasses of castrate resistant prostate cancer (CRPC), the epigenetic landscape of prostate cancer, the role of DNA repair gene mutations, advancing the use of germline genetics in clinical practice, radionuclides for imaging and therapy, advances in molecular imaging, and therapeutic strategies for successful use of immunotherapy in advanced prostate cancer. This article reviews the presentations and discussions from the 2017 CHPCA Meeting in order to disseminate this knowledge and accelerate new biological understandings and advances in the treatment of patients with metastatic prostate cancer. © 2017 Wiley Periodicals, Inc.

  10. URG11 Regulates Prostate Cancer Cell Proliferation, Migration, and Invasion

    Directory of Open Access Journals (Sweden)

    Bin Pan

    2018-01-01

    Full Text Available Upregulated gene 11 (URG11, a new gene upregulated by hepatitis B virus X protein, is involved in the development and progression of several tumors, including liver, stomach, lung, and colon cancers. However, the role of URG11 in prostate cancer remains yet to be elucidated. By determined expression in human prostate cancer tissues, URG11 was found significantly upregulated and positively correlated with the severity of prostate cancer, compared with that in benign prostatic hyperplasia tissues. Further, the mRNA and protein levels of URG11 were significantly upregulated in human prostate cancer cell lines (DU145, PC3, and LNCaP, compared with human prostate epithelial cell line (RWPE-1. Moreover, by the application of siRNA against URG11, the proliferation, migration, and invasion of prostate cancer cells were markedly inhibited. Genetic knockdown of URG11 also induced cell cycle arrest at G1/S phase, induced apoptosis, and decreased the expression level of β-catenin in prostate cancer cells. Overexpression of URG11 promoted the expression of β-catenin, the growth, the migration, and invasion ability of prostate cancer cells. Taken together, this study reveals that URG11 is critical for the proliferation, migration, and invasion in prostate cancer cells, providing the evidence of URG11 to be a novel potential therapeutic target of prostate cancer.

  11. Nanodiamond-DGEA peptide conjugates for enhanced delivery of doxorubicin to prostate cancer

    Directory of Open Access Journals (Sweden)

    Amanee D Salaam

    2014-07-01

    Full Text Available The field of nanomedicine has emerged as an approach to enhance the specificity and efficacy of cancer treatments as stand-alone therapies and in combination with standard chemotherapeutic treatment regimens. The current standard of care for metastatic cancer, doxorubicin (DOX, is presented with challenges, namely toxicity due to a lack of specificity and targeted delivery. Nano-enabled targeted drug delivery systems can provide an avenue to overcome these issues. Nanodiamonds (ND, in particular, have been researched over the past five years for use in various drug delivery systems but minimal work has been done that incorporates targeting capability. In this study, a novel targeted drug delivery system for bone metastatic prostate cancer was developed, characterized, and evaluated in vitro. NDs were conjugated with the Asp–Gly–Glu–Ala (DGEA peptide to target α2β1 integrins over-expressed in prostate cancers during metastasis. To facilitate drug delivery, DOX was adsorbed to the surface of the ND-DGEA conjugates. Successful preparation of the ND-DGEA conjugates and the ND-DGEA+DOX system was confirmed with transmission electron microscopy, hydrodynamic size, and zeta potential measurements. Since traditional DOX treatment regimens lack specificity and increased toxicity to normal tissues, the ND-DGEA conjugates were designed to distinguish between cells that overexpress α2β1 integrin, bone metastatic prostate cancers cells (PC3, and cells that do not, human mesenchymal stem cells (hMSC. Utilizing the ND-DGEA+DOX system, the efficacy of 1 µg/mL and 2 µg/mL DOX doses increased from 2.5% to 12% cell death and 11% to 34% cell death, respectively. These studies confirmed that the delivery and efficacy of DOX were enhanced by ND-DGEA conjugates. Thus, the targeted ND-DGEA+DOX system provides a novel approach for decreasing toxicity and drug doses.

  12. Association of body composition with outcome of docetaxel chemotherapy in metastatic prostate cancer: a retrospective review.

    Science.gov (United States)

    Wu, Weixin; Liu, Xiandong; Chaftari, Patrick; Cruz Carreras, Maria Teresa; Gonzalez, Carmen; Viets-Upchurch, Jayne; Merriman, Kelly; Tu, Shi-Ming; Dalal, Shalini; Yeung, Sai-Ching J

    2015-01-01

    Docetaxel, a lipophilic drug, is indicated for castration-resistant metastatic prostate cancer. Most men with such disease would have had androgen-deprivation therapy, which decreases muscle and increases body fat. Obesity and body composition changes may influence the outcomes of docetaxel therapy. We conducted a retrospective review of 333 patients with metastatic prostate cancer treated with docetaxel at a comprehensive cancer center between October 7, 2004 and December 31, 2012. Body composition parameters were measured based on the areas of muscle and adipose tissues in the visceral and subcutaneous compartments on CT images at L3-4 levels. Dose calculations, toxicity and adverse reaction profiles, and overall survival were analyzed. Obese patients were younger at the diagnosis of prostate cancer and had a shorter duration from diagnosis to docetaxel therapy. Analysis of body composition found that a high visceral fat-to-subcutaneous fat area ratio (VSR) was associated with poor prognosis but a high visceral fat-to-muscle area ratio (VMR) and high body mass index were associated with increased duration from starting docetaxel to death, allowing such men to catch up with patients with normal body mass index in overall survival from cancer diagnosis to death. Cox proportional hazard regression showed that age ≥65 years, high VSR, abnormal serum alkaline phosphatase, and >10% reduction of initial dosage were significant predictors of shorter time between starting docetaxel and death, and that high VMR, obesity, and weekly regimens were significant predictors of longer survival after docetaxel. Obese and overweight patients may benefit more from weekly docetaxel regimens using the reference dosage of 35 mg/m2 without empirical dosage reduction.

  13. Zoladex and flutamide versus orchiectomy in the treatment of advanced prostatic cancer. A combined analysis of two European studies, EORTC 30853 and DAPROCA 86

    DEFF Research Database (Denmark)

    Iversen, P; Suciu, S; Sylvester, R

    1990-01-01

    A total of 591 patients with advanced prostatic cancer have been randomized to either orchiectomy or treatment with zoladex 3.6 mg as a depot preparation combined with flutamide 250 mg tid in two European studies, EORTC protocol 30853 and DAPROCA 86. Identical design and comparable patient...... characteristics in the two studies have allowed combined analysis. A small but statistically significant difference in time to objective progression or death from prostatic cancer was found in favor of the combination treatment. However, time from objective progression to death was longer in the group initially...... allocated to orchiectomy. Thus, no difference between treatment groups in overall survival was found. As a conclusion, the combined androgen blockade was not superior to orchiectomy in the treatment of patients with advanced prostatic cancer....

  14. Prostate cancer-specific survival among warfarin users in the Finnish Randomized Study of Screening for Prostate Cancer.

    Science.gov (United States)

    Kinnunen, Pete T T; Murtola, Teemu J; Talala, Kirsi; Taari, Kimmo; Tammela, Teuvo L J; Auvinen, Anssi

    2017-08-29

    Venous thromboembolic events (VTE) are common in cancer patients and associated with higher mortality. In vivo thrombosis and anticoagulation might be involved in tumor growth and progression. We studied the association of warfarin and other anticoagulant use as antithrombotic medication and prostate cancer (PCa) death in men with the disease. The study included 6,537 men diagnosed with PCa during 1995-2009. Information on anticoagulant use was obtained from a national reimbursement registry. Cox regression with adjustment for age, PCa risk group, primary therapy and use of other medication was performed to compare risk of PCa death between warfarin users with 1) men using other types of anticoagulants and 2) non-users of anticoagulants. Medication use was analyzed as a time-dependent variable to minimize immortal time bias. In total, 728 men died from PCa during a median follow-up of 9 years. Compared to anticoagulant non-users, post-diagnostic use of warfarin was associated with an increased risk of PCa death (overall HR 1.47, 95% CI 1.13-1.93). However, this was limited to low-dose, low-intensity use. Otherwise, the risk was similar to anticoagulant non-users. Additionally, we found no risk difference between warfarin and other types of anticoagulants. Pre-diagnostic use of warfarin was not associated with the risk of PCa death. We found no reduction in risk of PCa death associated with warfarin use. Conversely, the risk was increased in short-term use, which is probably explained by a higher risk of thrombotic events prompting warfarin use in patients with terminal PCa.

  15. Disparities in Prostate Cancer Treatment Modality and Quality of Life

    Science.gov (United States)

    2010-11-01

    producing hormones) 1 0 10 11 B8f. Watchful waiting (no treatment, wait and see if your prostate cancer grows) 1 0 10 11 B8g. Cryotherapy (process...your prostate cancer grows) 7 Cryotherapy (process to freeze and destroy prostate tissue) 8 Chemotherapy (use of anti- cancer drugs) 9 Any other...and attitudes concerning prostate cancer and preventative measures. Prostate Cancer Questionnaire IRB1012# – Version 3 08/01/08 33 Now, I

  16. PVAMU/XULA/BCM Summer Prostate Cancer Research Program

    Science.gov (United States)

    2017-10-01

    degradation of several cancer -related proteins, including the androgen receptor , which is dysregulated in certain prostate cancers . Overall, the goal of my...Behavior of Androgen Receptor Splice Variants in Androgen Dependent Prostate Cancer Cells Turner, Williamson D., Xavier University of Louisiana, Class...AWARD NUMBER: W81XWH-15-1-0677 TITLE: PVAMU/XULA/BCM Summer Prostate Cancer Research Program PRINCIPAL INVESTIGATOR: Nancy L. Weigel

  17. Expression of KLK2 gene in prostate cancer

    Directory of Open Access Journals (Sweden)

    Sajad Shafai

    2018-01-01

    Conclusion: The expression of KLK2 gene in people with prostate cancer is the higher than the healthy person; finally, according to the results, it could be mentioned that the KLK2 gene considered as a useful factor in prostate cancer, whose expression is associated with progression and development of the prostate cancer.

  18. Survival benefit of early androgen receptor inhibitor therapy in locally advanced prostate cancer

    DEFF Research Database (Denmark)

    Thomsen, Frederik B; Brasso, Klaus; Christensen, Ib J

    2015-01-01

    BACKGROUND: The optimal timing of endocrine therapy in non-metastatic prostate cancer (PCa) is still an issue of debate. METHODS: A randomised, double-blind, parallel-group trial comparing bicalutamide 150mg once daily with placebo in addition to standard care in patients with hormone-naïve, non......-metastatic PCa. Kaplan-Meier analysis was used to estimate overall survival (OS) and multivariate Cox proportional hazard model was performed to analyse time-to-event (death). FINDINGS: A total of 1218 patients were included into the Scandinavian Prostate Cancer Group (SPCG)-6 study of which 607 were randomised...... disease (hazard ratios (HR)=0.77 (95% confidence interval (CI): 0.63-0.94, p=0.01), regardless of baseline prostate-specific antigen (PSA), with a survival benefit which was apparent throughout the study period. In contrast, survival favoured randomisation to the placebo arm in patients with localised...

  19. Primary radiation therapy in the treatment of localized prostatic cancer

    International Nuclear Information System (INIS)

    Joensuu, T.K.; Blomqvist, C.P.; Kajanti, M.J.

    1995-01-01

    Prostatic carcinoma is one of the leading causes of male cancer deaths. However, the routine diagnostic and therapeutic strategies have not yet been established. Although the outcome of surgical and radiotherapeutical approaches has frequently been reported to be comparable, the profile of side effects is different. This could offer the basis for selecting the treatment of choice in individual cases. During the last decade the radiotherapeutical technique has markedly improved, in part due to the achievements in the field of computer assisted tomography planning and conformal technique; the outcome of side-effects has decreased with concurrent increase in the rate of local control. The prescribing, recording and reporting of irradiation have also recently developed, as well as the staging of the disease. Therefore we consider it timely to review progress in this subject and to emphasize the role of radiotherapy in the treatment of localized prostatic cancer. (orig.)

  20. Hormone-refractory prostate cancer and the skeleton

    NARCIS (Netherlands)

    Soerdjbalie-Maikoe, Vidija

    2006-01-01

    Prostate cancer is the second most common cancer in men in the UK. Androgen ablation with luteinising hormone-releasing hormone agonists (LHRH agonists) alone, or in combination with anti-androgens is the standard treatment for men with metastatic prostate cancer. Unfortunately, despite maximal

  1. Physical activity and risk of prostate and bladder cancer in China: The South and East China case-control study on prostate and bladder cancer.

    Directory of Open Access Journals (Sweden)

    Raoul C Reulen

    Full Text Available Recent meta-analyses have suggested a modest protective effect of high levels of physical activity on developing both prostate and bladder cancer, but significant heterogeneity between studies included in these meta-analyses existed. To our knowledge, few Chinese studies investigated the association between physical activity and prostate cancer and none between physical activity and bladder cancer. Given the inconsistencies between previous studies and because studies on the relation between physical activity and prostate and bladder cancer in China are scarce, it remains elusive whether there is a relationship between physical activity and prostate and bladder cancer within the Chinese population.We investigated the association between physical activity and risk of developing prostate and bladder cancer within a hospital-based case-control study in the East and South of China among 260 and 438 incident prostate and bladder cancer cases, respectively, and 427 controls. A questionnaire was administered to measure physical activity as metabolic equivalents (METs. Random effects logistic regression was used to calculate odds ratios (ORs of prostate and bladder cancer for different levels of physical activity and for the specific activities of walking and cycling.Increasing overall physical activity was associated with a significant reduction in prostate cancer risk (Ptrend = 0.04 with the highest activity tertile level showing a nearly 50% reduction in prostate cancer risk (OR = 0.53, 95%CI: 0.28-0.98. Overall physical activity was not significantly associated with risk of bladder cancer (Ptrend = 0.61, neither were vigorous (Ptrend = 0.60 or moderate levels of physical activity (Ptrend = 0.21. Walking and cycling were not significantly associated with either prostate (Ptrend> = 0.62 or bladder cancer risk (Ptrend> = 0.25.The findings of this largest ever case-control study in China investigating the relationship between physical activity and

  2. Efficacy of c-Met inhibitor for advanced prostate cancer

    International Nuclear Information System (INIS)

    Tu, William H; Zhu, Chunfang; Clark, Curtis; Christensen, James G; Sun, Zijie

    2010-01-01

    Aberrant expression of HGF/SF and its receptor, c-Met, often correlates with advanced prostate cancer. Our previous study showed that expression of c-Met in prostate cancer cells was increased after attenuation of androgen receptor (AR) signalling. This suggested that current androgen ablation therapy for prostate cancer activates c-Met expression and may contribute to development of more aggressive, castration resistant prostate cancer (CRPC). Therefore, we directly assessed the efficacy of c-Met inhibition during androgen ablation on the growth and progression of prostate cancer. We tested two c-Met small molecule inhibitors, PHA-665752 and PF-2341066, for anti-proliferative activity by MTS assay and cell proliferation assay on human prostate cancer cell lines with different levels of androgen sensitivity. We also used renal subcapsular and castrated orthotopic xenograft mouse models to assess the effect of the inhibitors on prostate tumor formation and progression. We demonstrated a dose-dependent inhibitory effect of PHA-665752 and PF-2341066 on the proliferation of human prostate cancer cells and the phosphorylation of c-Met. The effect on cell proliferation was stronger in androgen insensitive cells. The c-Met inhibitor, PF-2341066, significantly reduced growth of prostate tumor cells in the renal subcapsular mouse model and the castrated orthotopic mouse model. The effect on cell proliferation was greater following castration. The c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer

  3. Current opinions on chemotherapy for prostate cancer

    International Nuclear Information System (INIS)

    Luptak, J.

    2011-01-01

    Prostate cancer is one of the most frequently diagnosed cancer among men. Because of the long latency period of prostate cancer, and the economic burden and morbidity associated with its treatment, there is a strong rationale for interventions to reduce the risk of developing this malignancy. The terms „prevention“ or „chemo prevention“ refers to efforts to prevent or delay the development of cancer by taking medicines, vitamins or other agents. There are many agents that may decrease the risk of prostate cancer. It requires careful study of the agents in specific populations to determine whether risk is reduced, magnitude of the risk reduction and the spectrum of side effects associated with the agent. The ideal preventive agent will not significantly alter quality of life, is inexpensive, safe, well tolerated, and effective. The purpose of this article is to review recent developments in the field of prostate cancer prevention. (author)

  4. Granulomatous prostatitis after intravesical immunotherapy mimicking prostate cancer

    Directory of Open Access Journals (Sweden)

    Waldemar Białek

    2016-12-01

    Full Text Available Intravesical immunotherapy with attenuated strains of Mycobacterium bovis is a widely used therapeutic option in patients with non-muscle-invasive transitional cell carcinoma of the bladder. A rare complication of intravesical therapy with the Bacillus Calmette-Guérin vaccine is granulomatous prostatitis, which due to increasing levels of prostate-specific antigen and abnormalities found in transrectal examination of the prostate may suggest concomitant prostate cancer. A case of extensive granulomatous prostatitis in a 61-year-old patient which occurred after the first course of a well-tolerated Bacillus Calmette-Guérin therapy is presented. Due to abnormalities found in rectal examination and an abnormal transrectal ultrasound image of the prostate with extensive infiltration mimicking neoplastic hyperplasia a core biopsy of the prostate was performed. Histopathological examination revealed inflammatory infiltration sites of tuberculosis origin.

  5. Definition of molecular determinants of prostate cancer cell bone extravasation.

    Science.gov (United States)

    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.

  6. Polyunsaturated fatty acids and prostate cancer risk

    DEFF Research Database (Denmark)

    Khankari, Nikhil K; Murff, Harvey J; Zeng, Chenjie

    2016-01-01

    BACKGROUND: Prostate cancer is a common cancer worldwide with no established modifiable lifestyle factors to guide prevention. The associations between polyunsaturated fatty acids (PUFAs) and prostate cancer risk have been inconsistent. Using Mendelian randomisation, we evaluated associations...... and prostate cancer risk. However, risk reductions were observed for short-chain PUFAs, linoleic (ORLA=0.95, 95%CI=0.92, 0.98) and α-linolenic acids (ORALA=0.96, 95%CI=0.93, 0.98), among men ...-chain PUFAs (i.e., arachidonic, eicosapentaenoic, and docosapentaenoic acids), increased risks were observed among men

  7. [Molecular biology of castration-resistant prostate cancer].

    Science.gov (United States)

    Doucet, Ludovic; Terrisse, Safae; Gauthier, Hélène; Pouessel, Damien; Le Maignan, Christine; Teixeira, Luis; Culine, Stéphane

    2015-06-01

    Castration-resistant prostate cancer was subjected to a paradigm switch from hormone resistance to androgen deprivation therapy resistance during the last decade. Indeed, new therapeutics targeting the androgen receptor showed clinical efficacy in patients with progressive disease under castration. Thus, it is a proof that the AR remains a dominant driver of oncogenesis in earlier-called hormone resistant prostate cancer. This review summarizes the molecular mechanisms involved in castration-resistant prostate cancer. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  8. Effects of gamma-radiation on cell growth, cycle arrest, death, and superoxide dismutase expression by DU 145 human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Vucic V.

    2006-01-01

    Full Text Available Gamma-irradiation (gamma-IR is extensively used in the treatment of hormone-resistant prostate carcinoma. The objective of the present study was to investigate the effects of 60Co gamma-IR on the growth, cell cycle arrest and cell death of the human prostate cancer cell line DU 145. The viability of DU 145 cells was measured by the Trypan blue exclusion assay and the 3(4,5-dimethylthiazol-2-yl-2,5,diphenyltetrazolium bromide test. Bromodeoxyuridine incorporation was used for the determination of cell proliferation. Cell cycle arrest and cell death were analyzed by flow cytometry. Superoxide dismutase (SOD, specifically CuZnSOD and MnSOD protein expression, after 10 Gy gamma-IR, was determined by Western immunoblotting analysis. gamma-IR treatment had a significant (P < 0.001 antiproliferative and cytotoxic effect on DU 145 cells. Both effects were time and dose dependent. Also, the dose of gamma-IR which inhibited DNA synthesis and cell proliferation by 50% was 9.7 Gy. Furthermore, gamma-IR induced cell cycle arrest in the G2/M phase and the percentage of cells in the G2/M phase was increased from 15% (control to 49% (IR cells, with a nonsignificant induction of apoptosis. Treatment with 10 Gy gamma-IR for 24, 48, and 72 h stimulated CuZnSOD and MnSOD protein expression in a time-dependent manner, approximately by 3- to 3.5-fold. These data suggest that CuZnSOD and MnSOD enzymes may play an important role in the gamma-IR-induced changes in DU 145 cell growth, cell cycle arrest and cell death.

  9. Transrectal ultrasound in detecting prostate cancer compared with serum total prostate-specific antigen levels

    International Nuclear Information System (INIS)

    Tamsel, S.; Killi, R.; Demirpolat, G.; Hekimgil, M.; Soydan, S.; Altay, B.

    2008-01-01

    We carried out a retrospective study to review the efficiency of grey-scale transrectal ultrasonography (TRUS) in detecting prostate cancer compared with the data in recent published work, including alternative imaging methods of the prostate gland. Our study group consisted of 830 patients who underwent TRUS-guided biopsy of the prostate between May 2000 and June 2004. The relation between abnormal TRUS findings and serum total prostate-specific antigen (tPSA) levels was evaluated in patients with prostate cancer who were divided into three different groups according to serum tPSA levels. Group I included patients with tPSA levels of 4-9.9 ng/mL, group II included tPSA levels of 10-19.9 ng/mL and group III included patients with tPSA levels of 20 ng/mL or more. In general, TRUS detected 185 (64%) of 291 cancers with a specificity of 89%, a PPV of 76% and an accuracy of 80%. TRUS findings enabled the correct identification of 22 (56%) of the 39 cancers in group I, 28 (30%) of the 93 cancers in group II and 135 (85%) of the 159 cancers in group III. In conclusion, TRUS alone has a limited potential to identify prostate cancer, especially in patients with tPSA levels lower than 20 ng/mL. Therefore, increased numbers of systematically placed biopsy cores must be taken or alternative imaging methods are required to direct TRUS-guided biopsy for improving prostate cancer detection.

  10. C-type natriuretic peptide in prostate cancer

    DEFF Research Database (Denmark)

    Nielsen, Soeren Junge; Iversen, Peter; Rehfeld, Jens F.

    2009-01-01

    C-type natriuretic peptide (CNP) is expressed in the male reproductive organs in pigs. To examine whether the human prostate also expresses the CNP gene, we measured CNP and N-terminal proCNP in prostate cancer tissue extracts and performed immunohistochemical biopsy staining. Additionally, pro......CNP-derived peptides were quantitated in plasma from patients with prostate cancer. Blood was collected from healthy controls and patients before surgery for localized prostate cancer. Tissue extracts were prepared from tissue biopsies obtained from radical prostatectomy surgery. N-terminal proCNP, proCNP (1......-50) and CNP were measured in plasma and tissue extracts. Biopsies were stained for CNP-22 and N-terminal proCNP. Tissue extracts from human prostate cancer contained mostly N-terminal proCNP [median 5.3 pmol/g tissue (range 1.0-12.9)] and less CNP [0.14 pmol/g tissue (0.01-1.34)]. Immunohistochemistry...

  11. 78 FR 54745 - National Prostate Cancer Awareness Month, 2013

    Science.gov (United States)

    2013-09-06

    ... National Prostate Cancer Awareness Month, 2013 By the President of the United States of America A... Cancer Awareness Month, we remember those lost to prostate cancer, offer our support to patients and... the laws of the United States, do hereby proclaim September 2013 as National Prostate Cancer Awareness...

  12. Sexual activity and the risk of prostate cancer: Review article

    Directory of Open Access Journals (Sweden)

    Ahmed Fouad Kotb

    2015-09-01

    Full Text Available Introduction: Sexual activity can affect prostate cancer pathogenesis in a variety of ways; including the proposed high androgen status, risk of sexually transmitted infections and the potential effect of retained carcinogens within the prostatic cells. Methods: PubMed review of all publications concerning sexual activity and the risk of prostate cancer was done by two researchers. Results: Few publications could be detected and data were classified as a prostate cancer risk in association with either heterosexual or homosexual activities. Conclusion: Frequent ejaculation seems to be protective from the development of prostate cancer. Multiple sexual partners may be protective from prostate cancer, excluding the risk of sexually transmitted infections. Homosexual men are at a greater risk for the diagnosis of prostate cancer.

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

    Directory of Open Access Journals (Sweden)

    Cristiano Capurso

    2017-08-01

    Full Text Available 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

  14. The Prostate Cancer Intervention Versus Observation Trial: VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy with watchful waiting for men with clinically localized prostate cancer.

    Science.gov (United States)

    Wilt, Timothy J

    2012-12-01

    Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men. In the United States, 90% of men with prostate cancer are more than age 60 years, diagnosed by early detection with the prostate-specific antigen (PSA) blood test, and have disease believed confined to the prostate gland (clinically localized). Common treatments for clinically localized prostate cancer include watchful waiting (WW), surgery to remove the prostate gland (radical prostatectomy), external-beam radiation therapy and interstitial radiation therapy (brachytherapy), and androgen deprivation. Little is known about the relative effectiveness and harms of treatments because of the paucity of randomized controlled trials. The Department of Veterans Affairs/National Cancer Institute/Agency for Healthcare Research and Quality Cooperative Studies Program Study #407:Prostate Cancer Intervention Versus Observation Trial (PIVOT), initiated in 1994, is a multicenter randomized controlled trial comparing radical prostatectomy with WW in men with clinically localized prostate cancer. We describe the study rationale, design, recruitment methods, and baseline characteristics of PIVOT enrollees. We provide comparisons with eligible men declining enrollment and men participating in another recently reported randomized trial of radical prostatectomy vs WW conducted in Scandinavia. We screened 13 022 men with prostate cancer at 52 US medical centers for potential enrollment. From these, 5023 met initial age, comorbidity, and disease eligibility criteria, and a total of 731 men agreed to participate and were randomized. The mean age of enrollees was 67 years. Nearly one-third were African American. Approximately 85% reported that they were fully active. The median PSA was 7.8ng/mL (mean 10.2ng/mL). In three-fourths of men, the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise. Using previously developed tumor risk

  15. Prostate-specific antigen (PSA) as a possible biomarker in non-prostatic cancer: A review.

    Science.gov (United States)

    Pérez-Ibave, Diana Cristina; Burciaga-Flores, Carlos Horacio; Elizondo-Riojas, Miguel-Ángel

    2018-06-01

    Prostate-specific antigen (PSA) is a serine protease produced by epithelial prostatic cells and its main function is to liquefy seminal coagulum. Currently, PSA is a biomarker for the diagnosis and screening of prostate cancer and it was the first cancer biomarker approved by the FDA. The quantity and serum isoforms of male PSA, allows distinguishing between carcinoma and benign inflammatory disease of the prostate. Initially, it was thought that PSA was produced only by the prostate, and thus, a protein that was expressed exclusively in men. However, several authors report that PSA is a protein that is expressed by multiple non-prostatic tissues not only in men but also in women. Some authors also report that in women, the expression of this protein is highly related to breast and colon cancer and therefore can act as a possible biomarker for early detection, diagnosis and prognosis of these cancers in women. In this review, we will focus on the characteristics of the PSA at a molecular level, its current clinical implications, the expression of this protein in non-prostatic tissues, and its relationship with cancer, especially in women. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Urtica dioica dichloromethane extract induce apoptosis from intrinsic pathway on human prostate cancer cells (PC3).

    Science.gov (United States)

    Mohammadi, A; Mansoori, B; Aghapour, M; Baradaran, B

    2016-03-31

    Prostate cancer is considered as the major cause of death among men around the world. There are a number of medicinal plants triggering apoptosis response in cancer cells, thus have a therapeutic potential. Therefore, further studies to characterize beneficial properties of these plants in order to introduce novel anti-cancer drugs are the interest of recent researches on the alternative medicine. On the other hand, due to traditional uses and availability of Urtica dioica extract, we decided to evaluate the efficacy of this medicinal herb on pc3 prostate cancer cell line. In the present study the cytotoxic effects of Urtica dioica extract were assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and trypan blue viability dye. Then, DNA fragmentation and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were exploited to measure cell death and apoptosis stage. The expression levels of caspase 3, caspase 9 and Bcl-2 genes were quantified by Real-Time PCR. Finally, Cell cycle was analyzed by flow cytometry. MTT assay showed that dichloromethanolic extract of Urtica dioica significantly inhibited the cell growth. According to the DNA fragmentation and TUNEL assay results, the herbal extract was able to induce apoptosis in prostate cancer cells. Our findings also demonstrated that the plant extract substantially increases the caspase 3 and 9 mRNA expression, while decreases Bcl-2. Cell cycle arrest was occurred in G2 stage, due to the results of flow cytometry. These results indicate that dichloromethanolic extract of Urtica dioica can successfully induce apoptosis in PC3 cells. Therefore, it could be used as a novel therapeutic candidate for prostate tumor treatment.

  17. Clinical Usefulness of the Histoculture Drug Response Assay for Prostate Cancer and Benign Prostate Hypertrophy (BPH).

    Science.gov (United States)

    Hoffman, Robert M

    2018-01-01

    The histoculture drug response assay (HDRA) has been adapted to determine androgen sensitivity in Gelfoam histoculture of human benign prostatic tissue as well as prostate cancer. Gelfoam histoculture was used to measure androgen-independent and androgen-dependent growth of benign and malignant prostate tissue. The androgen-sensitivity index was significantly higher in 23 paired specimens of prostate cancer compared to benign prostate hypertrophy (BPH). Genistein decreased the androgen-sensitivity index of BPH and prostate cancer in Gelfoam ® histoculture in a dose-dependent manner.

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

    Science.gov (United States)

    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.

  19. The Role of Estrogen Receptor β in Prostate Cancer

    OpenAIRE

    Christoforou, Paraskevi; Christopoulos, Panagiotis F; Koutsilieris, Michael

    2014-01-01

    Although androgen receptor (AR) signaling is the main molecular tool regulating growth and function of the prostate gland, estrogen receptor β (ERβ) is involved in the differentiation of prostatic epithelial cells and numerous antiproliferative actions on prostate cancer cells. However, ERβ splice variants have been associated with prostate cancer initiation and progression mechanisms. ERβ is promising as an anticancer therapy and in the prevention of prostate cancer. Herein, we review the re...

  20. Multiple primary cancers: Simultaneously occurring prostate cancer ...

    African Journals Online (AJOL)

    We also reviewed the existing literatures for possible biologic links between prostatic carcinoma and other primary tumors. ... The primary tumors co-existing with prostate cancer were colonic adenocarcinoma, rectal adenocarcinoma, urinary bladder transitional cell carcinoma, primary liver cell carcinoma, and thyroid ...

  1. Are strict vegetarians protected against prostate cancer?1

    Science.gov (United States)

    Knutsen, Synnove F; Knutsen, Raymond; Jacobsen, Bjarne K; Fan, Jing; Beeson, W Lawrence; Sabate, Joan; Hadley, David; Jaceldo-Siegl, Karen; Penniecook, Jason; Herring, Patti; Butler, Terry; Bennett, Hanni; Fraser, Gary

    2016-01-01

    Background: According to the American Cancer Society, prostate cancer accounts for ∼27% of all incident cancer cases among men and is the second most common (noncutaneous) cancer among men. The relation between diet and prostate cancer is still unclear. Because people do not consume individual foods but rather foods in combination, the assessment of dietary patterns may offer valuable information when determining associations between diet and prostate cancer risk. Objective: This study aimed to examine the association between dietary patterns (nonvegetarian, lacto-ovo-vegetarian, pesco-vegetarian, vegan, and semi-vegetarian) and prostate cancer incidence among 26,346 male participants of the Adventist Health Study-2. Design: In this prospective cohort study, cancer cases were identified by matching to cancer registries. Cox proportional hazards regression analysis was performed to estimate HRs by using age as the time variable. Results: In total, 1079 incident prostate cancer cases were identified. Around 8% of the study population reported adherence to the vegan diet. Vegan diets showed a statistically significant protective association with prostate cancer risk (HR: 0.65; 95% CI: 0.49, 0.85). After stratifying by race, the statistically significant association with a vegan diet remained only for the whites (HR: 0.63; 95% CI: 0.46, 0.86), but the multivariate HR for black vegans showed a similar but nonsignificant point estimate (HR: 0.69; 95% CI: 0.41, 1.18). Conclusion: Vegan diets may confer a lower risk of prostate cancer. This lower estimated risk is seen in both white and black vegan subjects, although in the latter, the CI is wider and includes the null. PMID:26561618

  2. TRAF4 and Castration-Resistant Prostate Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0536 TITLE: TRAF4 and Castration-Resistant Prostate Cancer PRINCIPAL INVESTIGATOR: Ping Yi CONTRACTING...Castration Resistant prostate cancer 5b. GRANT NUMBER W81XWH-15-1-0536 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Ping Yi 5d. PROJECT NUMBER 5e. TASK...to be a critical player in castration-resistant prostate cancers . It was suggested that the function of AR in CRPC is not to turn on the same

  3. Male pattern baldness and the risk of prostate cancer.

    Science.gov (United States)

    Yassa, M; Saliou, M; De Rycke, Y; Hemery, C; Henni, M; Bachaud, J M; Thiounn, N; Cosset, J M; Giraud, P

    2011-08-01

    Androgens play a role in the development of both androgenic alopecia, commonly known as male pattern baldness, and prostate cancer. We set out to study if early-onset androgenic alopecia was associated with an increased risk of prostate cancer later in life. A total of 669 subjects (388 with a history of prostate cancer and 281 without) were enrolled in this study. All subjects were asked to score their balding pattern at ages 20, 30 and 40. Statistical comparison was subsequently done between both groups of patients. Our study revealed that patients with prostate cancer were twice as likely to have androgenic alopecia at age 20 [odds ratio (OR) 2.01, P = 0.0285]. The pattern of hair loss was not a predictive factor for the development of cancer. There was no association between early-onset alopecia and an earlier diagnosis of prostate cancer or with the development of more aggressive tumors. This study shows an association between early-onset androgenic alopecia and the development of prostate cancer. Whether this population can benefit from routine prostate cancer screening or systematic use of 5-alpha reductase inhibitors as primary prevention remains to be determined.

  4. Development of Personalized Cancer Therapy for Men with AdvancedProstate Cancer

    Science.gov (United States)

    2016-10-01

    propose to study the mechanism of pharmacologic inhibition of the MLL complex in prostate cancer cells 3) we will assess the in vivo efficacy of the...Project Goals: 1) Enroll patients with known or suspicious for prostate cancer in the NIH MRI /metabolic imaging program, 2) Whole exome and...Henderson 02/11/2014-01/31/2017 Project Goals: 1) Enroll patients with known or suspicious for prostate cancer in the NIH MRI /metabolic imaging program

  5. Prostate cancer in renal transplant recipients

    Directory of Open Access Journals (Sweden)

    Benjamin A. Sherer

    Full Text Available ABSTRACT As patients with end-stage renal disease are receiving renal allografts at older ages, the number of male renal transplant recipients (RTRs being diagnosed with prostate cancer (CaP is increasing. Historically, the literature regarding the management of CaP in RTR's is limited to case reports and small case series. To date, there are no standardized guidelines for screening or management of CaP in these complex patients. To better understand the unique characteristics of CaP in the renal transplant population, we performed a literature review of PubMed, without date limitations, using a combination of search terms including prostate cancer, end stage renal disease, renal transplantation, prostate cancer screening, prostate specific antigen kinetics, immuno-suppression, prostatectomy, and radiation therapy. Of special note, teams facilitating the care of these complex patients must carefully and meticulously consider the altered anatomy for surgical and radiotherapeutic planning. Active surveillance, though gaining popularity in the general low risk prostate cancer population, needs further study in this group, as does the management of advance disease. This review provides a comprehensive and contemporary understanding of the incidence, screening measures, risk stratification, and treatment options for CaP in RTRs.

  6. Testicular Metastasis of Prostate Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Ayumu Kusaka

    2014-09-01

    Full Text Available The incidence of secondary neoplasms of the testis during autopsies is approximately 2.5%. Although most secondary testicular metastases are due to prostate cancer, only a few patients with prostate cancer have clinically manifested testicular metastasis. We report the case of a prostate cancer patient with testicular metastasis who was diagnosed after the presence of a palpable mass in the right testis. A 56-year-old Japanese male presented to our hospital with an elevated serum prostate-specific antigen (PSA level of 137 ng/ml. He was diagnosed with stage IV (T3N1M1b prostate cancer and received androgen deprivation therapy, followed by various hormonal manipulations. His serum PSA level was undetectable for 1 year. No distant metastases were detected during imaging examinations. He received radiation therapy; however, his serum PSA level increased gradually. Four months later, he presented with right testicular swelling. Computed tomography revealed a heterogenous mass in the right testis and a right high inguinal orchiectomy was performed. Histopathological analysis showed that the right testis was infiltrated with metastatic adenocarcinoma with a Gleason score of 8. This is a rare case of right testicular metastasis in a patient with prostate cancer. Testicular metastasis of prostate cancer can be aggressive and metastasize.

  7. Radical prostatectomy for high-risk prostate cancer.

    Science.gov (United States)

    Yossepowitch, Ofer; Eastham, James A

    2008-06-01

    Consensus recommendations for the identification and treatment of men whose apparent organ confined prostate cancer has high risk features are lacking. Despite ongoing refinements in surgical technique and improvements in morbidity and functional outcomes, the tradition of steering high-risk patients away from radical prostatectomy (RP) remains steadfast. We performed a medical literature search in English using MEDLINE/PubMed that addressed high risk prostate cancer. We analyzed the literature with respect to the historical evolution of this concept, current risk stratification schemes and treatment guidelines and related short and long term outcomes following RP. Contemporary evidence suggest that patients classified with high-risk prostate cancer by commonly used definitions do not have a uniformly poor prognosis after RP. Many cancers categorized clinically as high risk are actually pathologically confined to the prostate, and most men with such cancers who undergo RP are alive and free of additional therapy long after surgery. RP in the high-risk setting appears to be associated with a similar morbidity as in lower-risk patients. Men with clinically localized high-risk prostate cancer should not be categorically disqualified from local definitive therapy with RP. With careful attention to surgical technique, cancer control rates should improve further, and adverse effects on quality of life after RP should continue to decrease.

  8. Zoladex and flutamide versus orchiectomy in the treatment of advanced prostatic cancer. A combined analysis of two European studies, EORTC 30853 and DAPROCA 86

    DEFF Research Database (Denmark)

    Iversen, P; Suciu, S; Sylvester, R

    1990-01-01

    A total of 591 patients with advanced prostatic cancer have been randomized to either orchiectomy or treatment with zoladex 3.6 mg as a depot preparation combined with flutamide 250 mg tid in two European studies, EORTC protocol 30853 and DAPROCA 86. Identical design and comparable patient...... characteristics in the two studies have allowed combined analysis. A small but statistically significant difference in time to objective progression or death from prostatic cancer was found in favor of the combination treatment. However, time from objective progression to death was longer in the group initially...

  9. Natural History of Untreated Prostate Specific Antigen Radiorecurrent Prostate Cancer in Men with Favorable Prognostic Indicators

    Directory of Open Access Journals (Sweden)

    Neil E. Martin

    2014-01-01

    Full Text Available Background and Purpose. Life expectancy data could identify men with favorable post-radiation prostate-specific antigen (PSA failure kinetics unlikely to require androgen deprivation therapy (ADT. Materials and Methods. Of 206 men with unfavorable-risk prostate cancer in a randomized trial of radiation versus radiation and ADT, 53 experienced a PSA failure and were followed without salvage ADT. Comorbidity, age and established prognostic factors were assessed for relationship to death using Cox regression analyses. Results. The median age at failure, interval to PSA failure, and PSA doubling time were 76.6 years (interquartile range [IQR]: 71.8–79.3, 49.1 months (IQR: 37.7–87.4, and 25 months (IQR: 13.1–42.8, respectively. After a median follow up of 4.0 years following PSA failure, 45% of men had died, none from prostate cancer and no one had developed metastases. Both increasing age at PSA failure (HR: 1.14; 95% CI: 1.03–1.25; P=0.008 and the presence of moderate to severe comorbidity (HR: 12.5; 95% CI: 3.81–41.0; P2 years following post-radiation PSA failure appear to be good candidates for observation without ADT intervention.

  10. Analysis of contrast-enhanced ultrasonography using time-intensity curves in prostatic hyperplasia and prostate cancer

    International Nuclear Information System (INIS)

    Fang Junchu; Chen Ming; Sun Huifen

    2008-01-01

    Objective: To study the characters of time-intensity curve of contrast-enhanced ultrasonography in benign prostate hyperplasia (BPH) and prostate cancer. Methods: 2.4 ml Sono Vue were injected as a bolus in 40 patients, 23 patients with BPH and 17 with prostate cancer. High perfusion area in both inner and outer gland were measured with time-intensity curves. Results: It was proved by the time-intensity curves that, in BPH cases, the outer prostate gland presented with mild enhancedment and slow wash-off, while the inner gland presented with moderate enhancedment and fast wash-off. Otherwise, both the inner and outer gland in prostate cancer cases presented with high-intensitive enhancedment and slow wash-off. There was marked difference statistical significance on the up slop, average intensity and area under the time-intensity curves in 90 s and 150 s between the cases of BPH and prostate cancer (P<0.05, P<0.01). Conclusion: Quantitative analysis of high perfusion area in both inner and outer glands is helpful for diagnosing BPH and prostate cancer. (authors)

  11. Multiparametric MRI of the prostate. Method for early detection of prostate cancer?

    International Nuclear Information System (INIS)

    Schlemmer, Heinz-Peter

    2010-01-01

    Current approaches for the early detection of prostate cancer are controversially discussed because the disease is characterized by a high incidence rate with a relatively low morbidity rate, availability of only limited prognostic markers, and continued therapy-related morbidity. Conventional morphological MRI does not play a role in early detection since small tumor foci cannot be delineated. However, if there is clinical suspicion for prostate cancer, multiparametric MRI is currently the most accurate method for detecting and characterizing suspicious lesions in the prostate. The potential to identify the so-called 'index lesion', i.e., the tumor area that is most aggressive and determines treatment, is particularly important. This information can increase the accuracy of prostate biopsy and serve as a biomarker for follow-up during active surveillance. The method may considerably contribute to the urgently required separation of clinically significant from clinically insignificant prostate cancers. (orig.)

  12. Decision-making Processes among Prostate Cancer Survivors with Rising PSA Levels: Results from a Qualitative Analysis.

    Science.gov (United States)

    Shen, Megan Johnson; Nelson, Christian J; Peters, Ellen; Slovin, Susan F; Hall, Simon J; Hall, Matt; Herrera, Phapichaya Chaoprang; Leventhal, Elaine A; Leventhal, Howard; Diefenbach, Michael A

    2015-05-01

    Prostate cancer survivors with a rising prostate-specific antigen (PSA) level have few treatment options, experience a heightened state of uncertainty about their disease trajectory that might include the possibility of cancer metastasis and death, and often experience elevated levels of distress as they have to deal with a disease they thought they had conquered. Guided by self-regulation theory, the present study examined the cognitive and affective processes involved in shared decision making between physicians and patients who experience a rising PSA after definitive treatment for prostate cancer. In-depth interviews were conducted with 34 prostate cancer survivors who had been diagnosed with a rising PSA (i.e., biochemical failure) within the past 12 months. Survivors were asked about their experiences and affective responses after being diagnosed with a rising PSA and while weighing potential treatment options. In addition, patients were asked about their decision-making process for the initial prostate cancer treatment. Compared with the initial diagnosis, survivors with a rising PSA reported increased negative affect following their diagnosis, concern about the treatability of their disease, increased planning and health behavior change, heightened levels of worry preceding doctor appointments (especially prior to the discussion of PSA testing results), and a strong reliance on physicians' treatment recommendations. Prostate cancer survivors' decision-making processes for the treatment of a rising PSA are markedly different from those of the initial diagnosis of prostate cancer. Because patients experience heightened distress and rely more heavily on their physicians' recommendations with a rising PSA, interactions with the health care provider provide an excellent opportunity to address and assist patients with managing the uncertainty and distress inherent with rising PSA levels. © The Author(s) 2014.

  13. A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

    Directory of Open Access Journals (Sweden)

    Thorsten Schlomm

    2013-03-01

    Full Text Available We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA levels (14 and 17 individuals, respectively were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs. Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b, which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ.

  14. Localized prostate cancer in elderly men aged 80-89, findings from a population-based registry.

    Science.gov (United States)

    Vatandoust, S; Kichenadasse, G; O'Callaghan, M; Vincent, A D; Kopsaftis, T; Walsh, S; Borg, M; Karapetis, C S; Moretti, K

    2018-03-30

    To investigate the rate of death due to Prostate Cancer (PCa) and disease characteristics in patients diagnosed with Localized Prostate Cancer (LPCa) at age 80-89 years in comparison with men diagnosed at age 70-79. This is a retrospective study of data from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC). Included were men diagnosed between 2005 and 2014, aged ≥70 with no evidence of metastatic disease at presentation. Propensity score matching and competing risk Fine and Grey regression were used to assess the chance of treatment (curative v non-curative) and treatment effect on PCa specific-mortality. Of the 1951 eligible patients, 1428 (76%) aged 70-79, and 460 (24%) aged 80-89 yr at diagnosis (median age of 74 (IQR=72-76) and 83 (IQR=81-85) respectively). The 80-89 group had higher Gleason scores and PSA values (all pcopyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Intraductal Carcinoma of the Prostate on Diagnostic Needle Biopsy Predicts Prostate Cancer Mortality: A Population-Based Study.

    Science.gov (United States)

    Saeter, Thorstein; Vlatkovic, Ljiljana; Waaler, Gudmund; Servoll, Einar; Nesland, Jahn M; Axcrona, Karol; Axcrona, Ulrika

    2017-06-01

    Intraductal carcinoma of the prostate (IDC-P) is a distinct histopathologic feature associated with high-grade, advanced prostate cancer. Although studies have shown that IDC-P is a predictor of progression following surgical or radiation treatment for prostate cancer, there are sparse data regarding IDC-P on diagnostic needle biopsy as a prognosticator of prostate cancer mortality. This was a population-based study of all prostate cancer patients diagnosed using needle biopsy and without evidence of systemic disease between 1991 and 1999 within a defined geographic region of Norway. Patients were identified by cross-referencing the Norwegian Cancer Registry. Of 318 eligible patients, 283 had biopsy specimens available for central pathology review. Clinical data were obtained from medical charts. We examined whether IDC-P on diagnostic needle biopsy was associated with adverse clinicopathological features and prostate cancer mortality. Patients with IDC-P on diagnostic needle biopsy had a more advanced stage and a higher Gleason score compared to patients without IDC-P. IDC-P was also associated with an intensively reactive stroma. The 10-year prostate cancer-specific survival was 69% for patients with IDC-P on diagnostic needle biopsy and 89% for patients without IDC-P (Log rank P-value prostate cancer mortality after adjustments for clinical prognostic factors and treatment. After adjustment for the newly implemented Grade Group system of prostate cancer, IDC-P showed a strong tendency toward statistical significance. However, IDC-P did not remain a statistically significant predictor in the multivariable analysis. IDC-P on diagnostic needle biopsy is an indicator of prostate cancer with a high risk of mortality. Accordingly, a diagnosis of IDC-P on needle biopsy should be reported and considered a feature of high-risk prostate cancer. Moreover, the association between IDC-P and reactive stroma provides evidence in support of the idea that stromal factors

  16. Germline Variation in HSD3B1 as a Novel Biomarker in Prostate Cancer

    Science.gov (United States)

    2017-10-01

    or regional nodal recurrence on physical examination, CT, or MRI ; distant metastasis seen on bone scan, CT, or MRI ; or death from prostate cancer...provide insight regarding the potential eff ect of pharmacological inhibition of 3βHSD1. Because of the quite low prevalence of the homozygous variant

  17. Prostate atypia: does repeat biopsy detect clinically significant prostate cancer?

    Science.gov (United States)

    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.

  18. Saposin C promotes survival and prevents apoptosis via PI3K/Akt-dependent pathway in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Lee Tae-Jin

    2004-11-01

    Full Text Available Abstract Background In addition to androgens, growth factors are also implicated in the development and neoplastic growth of the prostate gland. Prosaposin is a potent neurotrophic molecule. Homozygous inactivation of prosaposin in mice has led to the development of a number of abnormalities in the male reproductive system, including atrophy of the prostate gland and inactivation of mitogen-activated protein kinase (MAPK and Akt in prostate epithelial cells. We have recently reported that prosaposin is expressed at a higher level by androgen-independent (AI prostate cancer cells as compared to androgen-sensitive prostate cancer cells or normal prostate epithelial and stromal cells. In addition, we have demonstrated that a synthetic peptide (prosaptide TX14A, derived from the trophic sequence of the saposin C domain of prosaposin, stimulated cell proliferation, migration and invasion and activated the MAPK signaling pathway in prostate cancer cells. The biological significances of saposin C and prosaposin in prostate cancer are not known. Results Here, we report that saposin C, in a cell type-specific and dose-dependent manner, acts as a survival factor, activates the Akt-signaling pathway, down-modulates caspase-3, -7, and -9 expression and/or activity, and decreases the cleaved nuclear substrate of caspase-3 in prostate cancer cells under serum-starvation stress. In addition, prosaptide TX14A, saposin C, or prosaposin decreased the growth-inhibitory effect, caspase-3/7 activity, and apoptotic cell death induced by etoposide. We also discovered that saposin C activates the p42/44 MAP kinase pathway in a pertussis toxin-sensitive and phosphatidylinositol 3-kinase (PI3K /Akt-dependent manner in prostate cancer cells. Our data also show that the anti-apoptotic activity of saposin C is at least partially mediated via PI3K/Akt signaling pathway. Conclusion We postulate that as a mitogenic, survival, and anti-apoptotic factor for prostate cancer cells

  19. Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kiessling, Andrea [Biologics Safety and Disposition, Preclinical Safety, Translational Sciences, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Werk Klybeck, Klybeckstraße 141, Basel CH-4057 (Switzerland); Wehner, Rebekka [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Füssel, Susanne [Department of Urology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Bachmann, Michael [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Wirth, Manfred P. [Department of Urology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Schmitz, Marc, E-mail: marc.schmitz@tu-dresden.de [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany)

    2012-02-22

    Prostate cancer (PCa) is the most common noncutaneous cancer diagnosis and the second leading cause of cancer-related deaths among men in the United States. Effective treatment modalities for advanced metastatic PCa are limited. Immunotherapeutic strategies based on T cells and antibodies represent interesting approaches to prevent progression from localized to advanced PCa and to improve survival outcomes for patients with advanced disease. CD8{sup +} cytotoxic T lymphocytes (CTLs) efficiently recognize and destroy tumor cells. CD4{sup +} T cells augment the antigen-presenting capacity of dendritic cells and promote the expansion of tumor-reactive CTLs. Antibodies mediate their antitumor effects via antibody-dependent cellular cytotoxicity, activation of the complement system, improving the uptake of coated tumor cells by phagocytes, and the functional interference of biological pathways essential for tumor growth. Consequently, several tumor-associated antigens (TAAs) have been identified that represent promising targets for T cell- or antibody-based immunotherapy. These TAAs comprise proteins preferentially expressed in normal and malignant prostate tissues and molecules which are not predominantly restricted to the prostate, but are overexpressed in various tumor entities including PCa. Clinical trials provide evidence that specific immunotherapeutic strategies using such TAAs represent safe and feasible concepts for the induction of immunological and clinical responses in PCa patients. However, further improvement of the current approaches is required which may be achieved by combining T cell- and/or antibody-based strategies with radio-, hormone-, chemo- or antiangiogenic therapy.

  20. Childhood height, adult height, and the risk of prostate cancer

    DEFF Research Database (Denmark)

    Bjerregaard, Lise Geisler; Aarestrup, Julie; Gamborg, Michael

    2016-01-01

    PURPOSE: We previously showed that childhood height is positively associated with prostate cancer risk. It is, however, unknown whether childhood height exerts its effects independently of or through adult height. We investigated whether and to what extent childhood height has a direct effect...... on the risk of prostate cancer apart from adult height. METHODS: We included 5,871 men with height measured at ages 7 and 13 years in the Copenhagen School Health Records Register who also had adult (50-65 years) height measured in the Danish Diet, Cancer and Health study. Prostate cancer status was obtained...... through linkage to the Danish Cancer Registry. Direct and total effects of childhood height on prostate cancer risk were estimated from Cox regressions. RESULTS: From 1996 to 2012, 429 prostate cancers occurred. Child and adult heights were positively and significantly associated with prostate cancer risk...

  1. MicroRNAs as new Characters in the Plot between Epigenetics and Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Alessio ePaone

    2011-09-01

    Full Text Available Prostate cancer (PCA still represents a leading cause of death. An increasing number of studies have documented that microRNAs (miRNAs, a subgroup of non-coding RNAs with gene regulatory functions, are differentially expressed in PCA respect to the normal tissue counterpart, suggesting their involvement in prostate carcinogenesis and dissemination. Interestingly, it has been shown that miRNAs undergo the same regulatory mechanisms than any other protein coding gene, including epigenetic regulation. In turn, miRNAs can also affect the expression of oncogenes and tumor suppressor genes by targeting effectors of the epigenetic machinery, therefore indirectly affecting the epigenetic controls on these genes. Among the genes that undergo this complex regulation, there is the androgen receptor (AR, a key therapeutic target for PCA. This review will focus on the role of epigenetically regulated and epigenetically regulating miRNAs in prostate cancer and on the fine regulation of AR expression, as mediated by this miRNA-epigenetics interaction.

  2. Epigenetic susceptibility factors for prostate cancer with aging.

    Science.gov (United States)

    Damaschke, N A; Yang, B; Bhusari, S; Svaren, J P; Jarrard, D F

    2013-12-01

    Increasing age is a significant risk factor for prostate cancer. The prostate is exposed to environmental and endogenous stress that may underlie this remarkable incidence. DNA methylation, genomic imprinting, and histone modifications are examples of epigenetic factors known to undergo change in the aging and cancerous prostate. In this review we examine the data linking epigenetic alterations in the prostate with aging to cancer development. An online search of current and past peer reviewed literature on epigenetic changes with cancer and aging was performed. Relevant articles were analyzed. Epigenetic changes are responsible for modifying expression of oncogenes and tumor suppressors. Several of these changes may represent a field defect that predisposes to cancer development. Focal hypermethylation occurs at CpG islands in the promoters of certain genes including GSTP1, RARβ2, and RASSF1A with both age and cancer, while global hypomethylation is seen in prostate cancer and known to occur in the colon and other organs. A loss of genomic imprinting is responsible for biallelic expression of the well-known Insulin-like Growth Factor 2 (IGF2) gene. Loss of imprinting (LOI) at IGF2 has been documented in cancer and is also known to occur in benign aging prostate tissue marking the presence of cancer. Histone modifications have the ability to dictate chromatin structure and direct gene expression. Epigenetic changes with aging represent molecular mechanisms to explain the increased susceptibly of the prostate to develop cancer in older men. These changes may provide an opportunity for diagnostic and chemopreventive strategies given the epigenome can be modified. © 2013 Wiley Periodicals, Inc.

  3. C-C motif ligand 5 promotes migration of prostate cancer cells in the prostate cancer bone metastasis microenvironment.

    Science.gov (United States)

    Urata, Satoko; Izumi, Kouji; Hiratsuka, Kaoru; Maolake, Aerken; Natsagdorj, Ariunbold; Shigehara, Kazuyoshi; Iwamoto, Hiroaki; Kadomoto, Suguru; Makino, Tomoyuki; Naito, Renato; Kadono, Yoshifumi; Lin, Wen-Jye; Wufuer, Guzailinuer; Narimoto, Kazutaka; Mizokami, Atsushi

    2018-03-01

    Chemokines and their receptors have key roles in cancer progression. The present study investigated chemokine activity in the prostate cancer bone metastasis microenvironment. Growth and migration of human prostate cancer cells were assayed in cocultures with bone stromal cells. The migration of LNCaP cells significantly increased when co-cultured with bone stromal cells isolated from prostate cancer bone metastases. Cytokine array analysis of conditioned medium from bone stromal cell cultures identified CCL5 as a concentration-dependent promoter of LNCaP cell migration. The migration of LNCaP cells was suppressed when C-C motif ligand 5 (CCL5) neutralizing antibody was added to cocultures with bone stromal cells. Knockdown of androgen receptor with small interfering RNA increased the migration of LNCaP cells compared with control cells, and CCL5 did not promote the migration of androgen receptor knockdown LNCaP. Elevated CCL5 secretion in bone stromal cells from metastatic lesions induced prostate cancer cell migration by a mechanism consistent with CCL5 activity upstream of androgen receptor signaling. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  4. Protocols for Migration and Invasion Studies in Prostate Cancer.

    Science.gov (United States)

    van de Merbel, Arjanneke F; van der Horst, Geertje; Buijs, Jeroen T; van der Pluijm, Gabri

    2018-01-01

    Prostate cancer is the most common malignancy diagnosed in men in the western world. The development of distant metastases and therapy resistance are major clinical problems in the management of prostate cancer patients. In order for prostate cancer to metastasize to distant sites in the human body, prostate cancer cells have to migrate and invade neighboring tissue. Cancer cells can acquire a migratory and invasive phenotype in several ways, including single cell and collective migration. As a requisite for migration, epithelial prostate cancer cells often need to acquire a motile, mesenchymal-like phenotype. This way prostate cancer cells often lose polarity and epithelial characteristics (e.g., expression of E-cadherin homotypic adhesion receptor), and acquire mesenchymal phenotype (for example, cytoskeletal rearrangements, enhanced expression of proteolytic enzymes and other repertory of integrins). This process is referred to as epithelial-to-mesenchymal transition (EMT). Cellular invasion, one of the hallmarks of cancer, is characterized by the movement of cells through a three-dimensional matrix, resulting in remodeling of the cellular environment. Cellular invasion requires adhesion, proteolysis of the extracellular matrix, and migration of cells. Studying the migratory and invasive ability of cells in vitro represents a useful tool to assess the aggressiveness of solid cancers, including those of the prostate.This chapter provides a comprehensive description of the Transwell migration assay, a commonly used technique to investigate the migratory behavior of prostate cancer cells in vitro. Furthermore, we will provide an overview of the adaptations to the Transwell migration protocol to study the invasive capacity of prostate cancer cells, i.e., the Transwell invasion assay. Finally, we will present a detailed description of the procedures required to stain the Transwell filter inserts and quantify the migration and/or invasion.

  5. Organoid cultures derived from patients with advanced prostate cancer

    NARCIS (Netherlands)

    Gao, Dong; Vela, Ian; Sboner, Andrea; Iaquinta, Phillip J; Karthaus, Wouter R; Gopalan, Anuradha; Dowling, Catherine; Wanjala, Jackline N; Undvall, Eva A; Arora, Vivek K; Wongvipat, John; Kossai, Myriam; Ramazanoglu, Sinan; Barboza, Luendreo P; Di, Wei; Cao, Zhen; Zhang, Qi Fan; Sirota, Inna; Ran, Leili; MacDonald, Theresa Y; Beltran, Himisha; Mosquera, Juan-Miguel; Touijer, Karim A; Scardino, Peter T; Laudone, Vincent P; Curtis, Kristen R; Rathkopf, Dana E; Morris, Michael J; Danila, Daniel C; Slovin, Susan F; Solomon, Stephen B; Eastham, James A; Chi, Ping; Carver, Brett; Rubin, Mark A; Scher, Howard I; Clevers, Hans; Sawyers, Charles L; Chen, Yu

    2014-01-01

    The lack of in vitro prostate cancer models that recapitulate the diversity of human prostate cancer has hampered progress in understanding disease pathogenesis and therapy response. Using a 3D organoid system, we report success in long-term culture of prostate cancer from biopsy specimens and

  6. Human RecQL4 helicase plays critical roles in prostate carcinogenesis

    DEFF Research Database (Denmark)

    Su, Yanrong; Meador, Jarah A; Calaf, Gloria M

    2010-01-01

    Prostate cancer is the second leading cause of cancer-associated deaths among men in the western countries. Here, we report that human RecQL4 helicase, which is implicated in the pathogenesis of a subset of cancer-prone Rothmund-Thomson syndrome, is highly elevated in metastatic prostate cancer c...

  7. Cytoreductive prostatectomy in metastatic prostate cancer

    DEFF Research Database (Denmark)

    Becker, Joachim Aidt; Berg, Kasper Drimer; Røder, Martin Andreas

    2018-01-01

    The impact of cytoreductive radical prostatectomy on oncological outcome in patients with prostate cancer and limited number of bone metastases is unclear. Data from cancer registries, multi-institutional databases and a single institutional case-control study indicate a possible benefit of combi......The impact of cytoreductive radical prostatectomy on oncological outcome in patients with prostate cancer and limited number of bone metastases is unclear. Data from cancer registries, multi-institutional databases and a single institutional case-control study indicate a possible benefit...

  8. Evaluation of Multimodal Imaging Biomarkers of Prostate Cancer

    Science.gov (United States)

    2016-11-01

    relationship prostate cancer growth, androgen receptor (AR) levels, hypoxia, and translocator protein (TSPO) levels. As described in the statement of work... bladder uptake) that enable robust detection of small prostate cancers . In contrast, high background and variable uptake of FDHT and FMISO confounded the...Award Number: W81XWH-12-1-0245 TITLE: Evaluation of Multimodal Imaging Biomarkers of Prostate Cancer PRINCIPAL INVESTIGATOR: Christopher Chad

  9. Effect of endocrine treatment on voiding and prostate size in men with prostate cancer

    DEFF Research Database (Denmark)

    Klarskov, Louise L; Klarskov, Peter; Mommsen, Søren

    2012-01-01

    The aim of this study was to assess and quantify changes in voiding parameters and prostate size in men with prostate cancer from before the start of endocrine treatment and during long-term follow-up.......The aim of this study was to assess and quantify changes in voiding parameters and prostate size in men with prostate cancer from before the start of endocrine treatment and during long-term follow-up....

  10. Molecular Signaling Pathways Mediating Osteoclastogenesis Induced by Prostate Cancer Cells

    International Nuclear Information System (INIS)

    Rafiei, Shahrzad; Komarova, Svetlana V

    2013-01-01

    Advanced prostate cancer commonly metastasizes to bone leading to osteoblastic and osteolytic lesions. Although an osteolytic component governed by activation of bone resorbing osteoclasts is prominent in prostate cancer metastasis, the molecular mechanisms of prostate cancer-induced osteoclastogenesis are not well-understood. We studied the effect of soluble mediators released from human prostate carcinoma cells on osteoclast formation from mouse bone marrow and RAW 264.7 monocytes. Soluble factors released from human prostate carcinoma cells significantly increased viability of naïve bone marrow monocytes, as well as osteoclastogenesis from precursors primed with receptor activator of nuclear factor κ-B ligand (RANKL). The prostate cancer-induced osteoclastogenesis was not mediated by RANKL as it was not inhibited by osteoprotegerin (OPG). However inhibition of TGFβ receptor I (TβRI), or macrophage-colony stimulating factor (MCSF) resulted in attenuation of prostate cancer-induced osteoclastogenesis. We characterized the signaling pathways induced in osteoclast precursors by soluble mediators released from human prostate carcinoma cells. Prostate cancer factors increased basal calcium levels and calcium fluctuations, induced nuclear localization of nuclear factor of activated t-cells (NFAT)c1, and activated prolonged phosphorylation of ERK1/2 in RANKL-primed osteoclast precursors. Inhibition of calcium signaling, NFATc1 activation, and ERK1/2 phosphorylation significantly reduced the ability of prostate cancer mediators to stimulate osteoclastogenesis. This study reveals the molecular mechanisms underlying the direct osteoclastogenic effect of prostate cancer derived factors, which may be beneficial in developing novel osteoclast-targeting therapeutic approaches

  11. Staging of prostate cancer: an update

    International Nuclear Information System (INIS)

    Vallejos, J.; Alvarez, C.; Mariluis, C.; Paganini, L.; González, C.; De Luca, S.; Dieguez, A.; Villaronga, A.

    2013-01-01

    In our country prostate cancer is the most common malignancy in older men. An accurate staging is very important to establish treatment strategies.This article presents the 7th edition TNM staging system for prostate cancer, effective January 1, 2010. This has undergone major changes over the 6th edition. (authors) [es

  12. Prostate Cancer Research Trial Helps John Spencer Treat His Cancer | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Prostate Cancer Prostate Cancer Research Trial Helps John Spencer Treat His Cancer ... because of timely detection and treatment of his prostate cancer. He participated in an NIH-sponsored clinical trial. ...

  13. Androgen receptor signaling is required for androgen-sensitive human prostate cancer cell proliferation and survival

    Directory of Open Access Journals (Sweden)

    Day Wanda V

    2005-04-01

    Full Text Available Abstract Background Androgens and androgen receptors (AR regulate normal prostate development and growth. They also are involved in pathological development of prostatic diseases, including benign prostatic hyperplasia (BPH and prostate cancer (PCa. Antiandrogen therapy for PCa, in conjunction with chemical or surgical castration, offers initial positive responses and leads to massive prostate cell death. However, cancer cells later appear as androgen-independent PCa. To investigate the role of AR in prostate cell proliferation and survival, we introduced a vector-based small interfering RNA (siRNA. This siRNA targeted 5'-untranslated region of AR mRNA for extended suppression of AR expression in androgen-sensitive human prostate LNCaP cells. Results The siRNA design successfully suppressed endogenous AR expression, as revealed by western blotting and immunofluorescence staining in LNCaP cells. LNCaP cells did not proliferate in the absence of AR and underwent apoptosis, based on elevated phospho-Histone H2B expression and higher number of apoptotic body as compared to control cells. Conclusion We demonstrated that AR is vital for prostate cell proliferation and survival in this androgen-sensitive prostate cell line. These results further strengthen the hypothesis that AR can be a therapeutic target for treating androgen-sensitive stages of PCa. Unlike antiandorgens, however, siRNA targeting AR provides a direct inactivation of AR function through the suppression of AR protein expression.

  14. Expression analysis of cancer-testis genes in prostate cancer reveals candidates for immunotherapy.

    Science.gov (United States)

    Faramarzi, Sepideh; Ghafouri-Fard, Soudeh

    2017-09-01

    Prostate cancer is a prevalent disorder among men with a heterogeneous etiological background. Several molecular events and signaling perturbations have been found in this disorder. Among genes whose expressions have been altered during the prostate cancer development are cancer-testis antigens (CTAs). This group of antigens has limited expression in the normal adult tissues but aberrant expression in cancers. This property provides them the possibility to be used as cancer biomarkers and immunotherapeutic targets. Several CTAs have been shown to be immunogenic in prostate cancer patients and some of the have entered clinical trials. Based on the preliminary data obtained from these trials, it is expected that CTA-based therapeutic options are beneficial for at least a subset of prostate cancer patients.

  15. Involvement of Bax and Bcl-2 in Induction of Apoptosis by Essential Oils of Three Lebanese Salvia Species in Human Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Alessandra Russo

    2018-01-01

    Full Text Available Prostate cancer is one of the most common forms of cancer in men, and research to find more effective and less toxic drugs has become necessary. In the frame of our ongoing program on traditionally used Salvia species from the Mediterranean Area, here we report the biological activities of Salvia aurea, S. judaica and S. viscosa essential oils against human prostate cancer cells (DU-145. The cell viability was measured by 3(4,5-dimethyl-thiazol-2-yl2,5-diphenyl-tetrazolium bromide (MTT test and lactate dehydrogenase (LDH release was used to quantify necrosis cell death. Genomic DNA, caspase-3 activity, expression of cleaved caspase-9, B-cell lymphoma 2 (Bcl-2 and Bcl-2 associated X (Bax proteins were analyzed in order to study the apoptotic process. The role of reactive oxygen species in cell death was also investigated. We found that the three essential oils, containing caryophyllene oxide as a main constituent, are capable of reducing the growth of human prostate cancer cells, activating an apoptotic process and increasing reactive oxygen species generation. These results suggest it could be profitable to further investigate the effects of these essential oils for their possible use as anticancer agents in prostate cancer, alone or in combination with chemotherapy agents.

  16. 77 FR 55099 - National Prostate Cancer Awareness Month, 2012

    Science.gov (United States)

    2012-09-06

    ... National Prostate Cancer Awareness Month, 2012 By the President of the United States of America A... thousands of lives every year. During National Prostate Cancer Awareness Month, we remember those we have... their lifetimes. As we mark National Prostate Cancer Awareness Month, let us support the families who...

  17. 76 FR 55551 - National Prostate Cancer Awareness Month, 2011

    Science.gov (United States)

    2011-09-07

    ... National Prostate Cancer Awareness Month, 2011 By the President of the United States of America A... observe National Prostate Cancer Awareness Month, we renew our commitment to reducing the impact of prostate cancer on our country by raising awareness and supporting research that will lead to better ways...

  18. The role of serum prostate specific antigen assayed by TRFIA in diagnosis of prostate cancer

    International Nuclear Information System (INIS)

    Deng Yongmei; Zhang Jinshan; Li Min

    2002-01-01

    The authors evaluate the diagnostic value of serum free prostate specific antigen (F-PSA), total-PSA(T-PSA) and free/total (F/T) PSA ratio in differentiation between benign and malignant prostatic diseases. Serum samples were measured by time-resolved fluoroimmunoassay (TRFIA), there were 86 patients whose T-PSA levels were limited within 2-20 ng/mL, from the results of prostate biopsies after operation, the patients were classified into two groups: the group with prostate hyperplasia (68 patients) and the group with prostate cancer (18 patients). The serum F-PSA and T-PSA of the two groups were analysed and compared, and the F/T PSA ratio was calculated. Results were: 1) the means of F-PSA and T-PSA were not significantly different between patients with prostate hyperplasia (BPH) and with prostate cancer (P>0.05), but the mean of F/T PSA ratio for prostate cancer was significantly lower than that for BPH (P<0.001); 2) sensitivity, specificity and positive predictive value for prostate cancer detection at a cutoff value of 0.18 for the F/T PSA ratio were 85%, 72.5% and 43.6%, respectively. Conclusion is the F/T PSA ratio may be used in differentiation prostate cancer from BPH, and when T-PSA level is within the range of 2-20 ng/mL, selecting 0.18 as the cutoff value has great clinical value

  19. Super-Penetrant Androgen Receptor: Overcoming Enzalutamide Sensitivity in Castration-Resistant Prostate Cancer

    Science.gov (United States)

    2016-07-01

    Prostate Cancer Research Symposium- Prostate Cancer Epigenetic Reprogramming of the Androgen Receptor in Castration Resistant Prostate Cancer , May19... cancer cells rely critically on the androgen receptor (AR) for initiation, growth and progression to castration resistant prostate cancer (CRPC...Androgen receptor, castration resistant prostate cancer , Enzalutamide , kinases. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER

  20. AR Signaling in Human Malignancies: Prostate Cancer and Beyond.

    Science.gov (United States)

    Antonarakis, Emmanuel S

    2018-01-18

    The notion that androgens and androgen receptor (AR) signaling are the hallmarks of prostate cancer oncogenesis and disease progression is generally well accepted. What is more poorly understood is the role of AR signaling in other human malignancies. This special issue of Cancers initially reviews the role of AR in advanced prostate cancer, and then explores the potential importance of AR signaling in other epithelial malignancies. The first few articles focus on the use of novel AR-targeting therapies in castration-resistant prostate cancer and the mechanisms of resistance to novel antiandrogens, and they also outline the interaction between AR and other cellular pathways, including PI3 kinase signaling, transcriptional regulation, angiogenesis, stromal factors, Wnt signaling, and epigenetic regulation in prostate cancer. The next several articles review the possible role of androgens and AR signaling in breast cancer, bladder cancer, salivary gland cancer, and hepatocellular carcinoma, as well as the potential treatment implications of using antiandrogen therapies in these non-prostatic malignancies.

  1. Activation of the intrinsic-apoptotic pathway in LNCaP prostate cancer cells by genistein- topotecan combination treatments

    Directory of Open Access Journals (Sweden)

    Vanessa Hörmann

    2013-03-01

    Full Text Available ABSTRACTBackground: Prostate cancer is the second most common cancer in American men. The development of alternative preventative and/or treatment options utilizing a combination of phytochemicals and chemotherapeutic drugs could be an attractive alternative compared to conventional carcinoma treatments. Genistein isoflavone is the primary dietary phytochemical found in soy and has demonstrated anti-tumor activities in LNCaP prostate cancer cells. Topotecan Hydrochloride (Hycamtin is an FDA-approved chemotherapy for secondary treatment of lung, ovarian and cervical cancers. The purpose of this study was to detail the potential activation of the intrinsic apoptotic pathway in LNCaP prostate cancer cells through genistein-topotecan combination treatments.Methods: LNCaP cells were cultured in complete RPMI medium in a monolayer (70-80% confluency at 37ºC and 5% CO2. Treatment consisted of single and combination groups of genistein and topotecan for 24 hours. The treated cells were assayed for i growth inhibition through trypan blue exclusion assay and microphotography , ii classification of cellular death through acridine/ ethidium bromide fluorescent staining, and iii activation of the intrinsic apoptotic pathway through Jc-1: mitochondrial membrane potential assay, cytochrome c release and Bcl-2 protein expression.Results: The overall data indicated that genistein-topotecan combination was significantly more efficacious in reducing the prostate carcinoma’s viability compared to the single treatment options. In all treatment groups, cell death occurred primarily through the activation of the intrinsic apoptotic pathway.Conclusion: The combination of topotecan and genistein has the potential to lead to treatment options with equal therapeutic efficiency as traditional chemo- and radiation therapies, but lower cell cytotoxicity and fewer side effects in patients.

  2. Autoantibody signatures as biomarkers to distinguish prostate cancer from benign prostatic hyperplasia in patients with increased serum prostate specific antigen.

    Science.gov (United States)

    O'Rourke, Dennis J; DiJohnson, Daniel A; Caiazzo, Robert J; Nelson, James C; Ure, David; O'Leary, Michael P; Richie, Jerome P; Liu, Brian C-S

    2012-03-22

    Serum prostate specific antigen (PSA) concentrations lack the specificity to differentiate prostate cancer from benign prostate hyperplasia (BPH), resulting in unnecessary biopsies. We identified 5 autoantibody signatures to specific cancer targets which might be able to differentiate prostate cancer from BPH in patients with increased serum PSA. To identify autoantibody signatures as biomarkers, a native antigen reverse capture microarray platform was used. Briefly, well-characterized monoclonal antibodies were arrayed onto nanoparticle slides to capture native antigens from prostate cancer cells. Prostate cancer patient serum samples (n=41) and BPH patient samples (collected starting at the time of initial diagnosis) with a mean follow-up of 6.56 y without the diagnosis of cancer (n=39) were obtained. One hundred micrograms of IgGs were purified and labeled with a Cy3 dye and incubated on the arrays. The arrays were scanned for fluorescence and the intensity was quantified. Receiver operating characteristic curves were produced and the area under the curve (AUC) was determined. Using our microarray platform, we identified autoantibody signatures capable of distinguishing between prostate cancer and BPH. The top 5 autoantibody signatures were TARDBP, TLN1, PARK7, LEDGF/PSIP1, and CALD1. Combining these signatures resulted in an AUC of 0.95 (sensitivity of 95% at 80% specificity) compared to AUC of 0.5 for serum concentration PSA (sensitivity of 12.2% at 80% specificity). Our preliminary results showed that we were able to identify specific autoantibody signatures that can differentiate prostate cancer from BPH, and may result in the reduction of unnecessary biopsies in patients with increased serum PSA. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Alcohol consumption and prostate cancer: a mini review.

    Science.gov (United States)

    Rizos, Ch; Papassava, M; Golias, Ch; Charalabopoulos, K

    2010-07-01

    Prostate cancer has become a major public health problem worldwide although the etiology of prostate cancer remains largely unknown. Dietary factors, dietary supplements, and physical activity might be important in the prevention of the disease. In the majority of studies published, it was observed that high consumption of meat, alcohol and dairy products has been linked to a greater risk. Specifically, alcohol use, and particularly heavy use, may cause cancers of liver, esophagus, larynx, pharynx and oral cavity, with risks for the aero-digestive cancers. Moderate use among women has been related with increases in breast cancer. Alcohol consumption is a modifiable lifestyle factor that may affect prostate cancer risk. Alcohol alters the hormonal environment and in parallel, containing chemical substances such as flavonoids (red wine), may alter tumor cell growth. In this mini review, the relation between alcohol consumption and prostate cancer risk is analyzed.

  4. A Pooled Analysis of 15 Prospective Cohort Studies on the Association between Fruit, Vegetable, and Mature Bean Consumption and Risk of Prostate Cancer.

    Science.gov (United States)

    Petimar, Joshua; Wilson, Kathryn M; Wu, Kana; Wang, Molin; Albanes, Demetrius; van den Brandt, Piet A; Cook, Michael B; Giles, Graham G; Giovannucci, Edward L; Goodman, Gary E; Goodman, Phyllis J; Håkansson, Niclas; Helzlsouer, Kathy; Key, Timothy J; Kolonel, Laurence N; Liao, Linda M; Männistö, Satu; McCullough, Marjorie L; Milne, Roger L; Neuhouser, Marian L; Park, Yikyung; Platz, Elizabeth A; Riboli, Elio; Sawada, Norie; Schenk, Jeannette M; Tsugane, Shoichiro; Verhage, Bas; Wang, Ying; Wilkens, Lynne R; Wolk, Alicja; Ziegler, Regina G; Smith-Warner, Stephanie A

    2017-08-01

    Background: Relationships between fruit, vegetable, and mature bean consumption and prostate cancer risk are unclear. Methods: We examined associations between fruit and vegetable groups, specific fruits and vegetables, and mature bean consumption and prostate cancer risk overall, by stage and grade, and for prostate cancer mortality in a pooled analysis of 15 prospective cohorts, including 52,680 total cases and 3,205 prostate cancer-related deaths among 842,149 men. Diet was measured by a food frequency questionnaire or similar instrument at baseline. We calculated study-specific relative risks using Cox proportional hazards regression, and then pooled these estimates using a random effects model. Results: We did not observe any statistically significant associations for advanced prostate cancer or prostate cancer mortality with any food group (including total fruits and vegetables, total fruits, total vegetables, fruit and vegetable juice, cruciferous vegetables, and tomato products), nor specific fruit and vegetables. In addition, we observed few statistically significant results for other prostate cancer outcomes. Pooled multivariable relative risks comparing the highest versus lowest quantiles across all fruit and vegetable exposures and prostate cancer outcomes ranged from 0.89 to 1.09. There was no evidence of effect modification for any association by age or body mass index. Conclusions: Results from this large, international, pooled analysis do not support a strong role of collective groupings of fruits, vegetables, or mature beans in prostate cancer. Impact: Further investigation of other dietary exposures, especially indicators of bioavailable nutrient intake or specific phytochemicals, should be considered for prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 26(8); 1276-87. ©2017 AACR . ©2017 American Association for Cancer Research.

  5. Prostate cancer incidence in Australia correlates inversely with solar radiation.

    Science.gov (United States)

    Loke, Tim W; Seyfi, Doruk; Sevfi, Doruk; Khadra, Mohamed

    2011-11-01

    What's known on the subject? and What does the study add? Increased sun exposure and blood levels of vitamin D have been postulated to be protective against prostate cancer. This is controversial. We investigated the relationship between prostate cancer incidence and solar radiation in non-urban Australia, and found a lower incidence in regions receiving more sunlight. In landmark ecological studies, prostate cancer mortality rates have been shown to be inversely related to ultraviolet radiation exposure. Investigators have hypothesised that ultraviolet radiation acts by increasing production of vitamin D, which inhibits prostate cancer cells in vitro. However, analyses of serum levels of vitamin D in men with prostate cancer have failed to support this hypothesis. This study has found an inverse correlation between solar radiation and prostate cancer incidence in Australia. Our population (previously unstudied) represents the third group to exhibit this correlation. Significantly, the demographics and climate of Australia differ markedly from those of previous studies conducted on men in the United Kingdom and the United States. • To ascertain if prostate cancer incidence rates correlate with solar radiation among non-urban populations of men in Australia. • Local government areas from each state and territory were selected using explicit criteria. Urban areas were excluded from analysis. • For each local government area, prostate cancer incidence rates and averaged long-term solar radiation were obtained. • The strength of the association between prostate cancer incidence and solar radiation was determined. • Among 70 local government areas of Australia, age-standardized prostate cancer incidence rates for the period 1998-2007 correlated inversely with daily solar radiation averaged over the last two decades. •  There exists an association between less solar radiation and higher prostate cancer incidence in Australia. © 2011 THE AUTHORS. BJU

  6. The bicalutamide Early Prostate Cancer Program. Demography

    DEFF Research Database (Denmark)

    See, W A.; McLeod, D; Iversen, P

    2001-01-01

    BACKGROUND: The optimal treatment for early prostate cancer has yet to be established. A well-tolerated hormonal therapy such as bicalutamide could be a useful treatment option in this setting, either as adjuvant or immediate therapy. A major collaborative clinical trials program was set up...... to investigate bicalutamide as a treatment option for local prostate cancer (localized or locally advanced disease). METHODS: The bicalutamide Early Prostate Cancer program comprises three randomized, double-blind, placebo-controlled trials of similar design that are being conducted in distinct geographical...... areas (North America; Australia, Europe, Israel, South Africa and Mexico; and Scandinavia). Men with T1b-4N0-1M0 (TNM 1997) prostate cancer have been randomized on a 1:1 basis to receive bicalutamide 150 mg daily or placebo. Recruitment to the program closed in July 1998, and follow-up is ongoing. Study...

  7. Predictors of participation in prostate cancer screening at worksites.

    Science.gov (United States)

    Weinrich, S P; Greiner, E; Reis-Starr, C; Yoon, S; Weinrich, M

    1998-01-01

    Unfortunately, African American men have a higher incidence of and a higher mortality rate for prostate cancer than White men but are less likely to participate in prostate cancer screening. This correlational survey research identifies predictors for participation in a free prostate cancer screening in 179 men, 64% of whom are African American. Each man was invited to see his personal physician for a free prostate cancer screening following a prostate cancer educational program given at his worksite. Forty-seven percent of the African American men went to their personal physician following the educational program and received a digital rectal examination (DRE) and a prostate specific antigen (PSA) screening. In the original cohort of educational program attendees, only 16% of the African Americans had obtained a DRE in the previous 12 months. However, 44% subsequently did participate in free DRE screening. Similarly, only 6% of the African American men had received a PSA screening in the previous 12 months, yet 42% obtained a PSA screening after the educational program, a sevenfold increase. Implications for allocating limited resources for education and screening to the high-risk group of African American men are discussed. This study's model of a prostate cancer educational program at worksites followed by attendees visiting their personal physician for screening could be replicated throughout the United States to increase African American men's participation in prostate cancer screening.

  8. Advanced Prostate Cancer Presenting as Hemolytic Uremic Syndrome

    Directory of Open Access Journals (Sweden)

    R. Ramos

    2013-01-01

    Full Text Available Introduction. Hemolytic uremic syndrome (HUS is characterized by endothelial dysfunction, consumption thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure. HUS generally has a dismal prognosis, except when associated with gastroenteritis caused by verotoxin-producing bacteria. Cancer associated HUS is uncommon, and there are only scarce reports on prostate cancer presenting with HUS. Case Presentation. A 72-year-old man presented to the emergency department with oliguria, hematuria, and hematemesis. Clinical evaluation revealed acute renal failure, hemolysis, normal blood-clotting studies, and prostate-specific antigen value of 1000 ng/mL. The patient was started on hemodialysis, ultrafiltration with plasma exchange, and androgen blockade with bicalutamide and completely recovered from HUS. The authors review the 14 published cases on this association. Conclusion. The association of HUS and prostate cancer occurs more frequently in patients with high-grade, clinically advanced prostate cancer. When readily recognized and appropriately treated, HUS does not seem to worsen prognosis in prostate cancer patients.

  9. COPING STRATEGIES IN PATIENTS WITH PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    J. R. Gardanova

    2015-01-01

    Full Text Available Diagnostics of psycho-emotional disorders of patients with malignant diseases of the prostate is not doubt, because timely correction contributes to the shortening of rehabilitation period and restoration of the quality of life of patients after treatment. Detection and diagnosis of prostate cancer for many patients is stressful and causes changes in the affective sphere, and manifests itself in increased levels of anxiety and depression in men. To cope with stress is possible due to the used coping strategies.Purpose. Studying the coping mechanisms in prostate cancer patients.Materials and methods. 56 men treated in FGBU "LRTS" Russian Ministry of Health. The average age was 65.7 ± 6.1 years. The average duration of the disease prostate cancer is 3 ± 2 months. All men were subjected to the standard algorithm for the evaluation of hormonal status, the PSA, taking a history, inspection and physical examination, magnetic resonance imaging and scintigraphy of bones of a skeleton. All the patients underwent laparoscopic radical prostatectomy. Psychological testing with the use of the method of "Coping test" the scale of reactive and personal anxiety for the differentiated evaluation of anxiety. Results. The most common for prostate cancer revealed constructive coping strategies are "planning solve", "selfcontrol" and "search of social support". According to the scale Spielberg–Hanin a high level of situational anxiety was revealed.Conclusion. According to the results of the research, patients with prostate cancer are likely to use constructive coping strategies, that leads to stabilization of psycho-emotional state of men and promotes more effective adaptation in the terms of stress, that is caused by treatment of prostate cancer.

  10. Lycopene, tomato products and prostate cancer-specific mortality among men diagnosed with nonmetastatic prostate cancer in the Cancer Prevention Study II Nutrition Cohort.

    Science.gov (United States)

    Wang, Ying; Jacobs, Eric J; Newton, Christina C; McCullough, Marjorie L

    2016-06-15

    While dietary lycopene and tomato products have been inversely associated with prostate cancer incidence, there is limited evidence for an association between consumption of lycopene and tomato products and prostate-cancer specific mortality (PCSM). We examined the associations of prediagnosis and postdiagnosis dietary lycopene and tomato product intake with PCSM in a large prospective cohort. This analysis included men diagnosed with nonmetastatic prostate cancer between enrollment in the Cancer Prevention Study II Nutrition Cohort in 1992 or 1993 and June 2011. Prediagnosis dietary data, collected at baseline, were available for 8,898 men, of whom 526 died of prostate cancer through 2012. Postdiagnosis dietary data, collected on follow-up surveys in 1999 and/or 2003, were available for 5,643 men, of whom 363 died of prostate cancer through 2012. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for PCSM. Neither prediagnosis nor postdiagnosis dietary lycopene intake was associated with PCSM (fourth vs. first quartile HR = 1.00, 95% CI 0.78-1.28; HR = 1.22, 95% CI 0.91-1.64, respectively). Similarly, neither prediagnosis nor postdiagnosis consumption of tomato products was associated with PCSM. Among men with high-risk cancers (T3-T4 or Gleason score 8-10, or nodal involvement), consistently reporting lycopene intake ≥ median on both postdiagnosis surveys was associated with lower PCSM (HR = 0.41, 95% CI 0.17-0.99, based on ten PCSM cases consistently ≥ median intake) compared to consistently reporting intake lycopene intake with PCSM among men with high-risk prostate cancers. © 2016 UICC.

  11. Educating men about prostate cancer in the workplace.

    Science.gov (United States)

    Ilic, Dragan

    2013-07-01

    Prostate cancer is a common cancer affecting men worldwide. Few men access health services with respect to early detection. Workplace health education initiatives can promote behavior change in men. A total of 12 in-depth interviews with men were conducted in this study to examine how a workplace-based educational campaign on prostate cancer influences the knowledge, awareness, and beliefs of male workers on screening for prostate cancer. Analyses of interview transcripts identified that men had a poor overall knowledge about prostate cancer, its screening, and treatment. Participants were receptive to the introduction of workplace-based health education initiatives to promote men's health issues but recommended an integrated health approach that incorporated information delivered by medical professionals, cancer survivors, supplemented with existing patient education materials. Further research is required to formally evaluate the impact of workplace-based education strategies on men's health.

  12. Psychosocial Intervention In Prostate Cancer Patients

    Directory of Open Access Journals (Sweden)

    Potočníková Jana

    2015-05-01

    Full Text Available Prostate cancer is the second most common cancer worldwide for males, and the fifth most common cancer overall. Using of autogenic training could reduce the influence of ADT and raise quality of prostate cancer patients. The aim of this study was to determine the effects of autogenic training in patients with prostate cancer. Patients were divided to experimental and control group. Experimental group participated in fourteen weeks long autogenic training program. Control group performed usual daily activities. Every subject of research performed input and output diagnostics which monitored psychical states of patients by psychological standardized tests - Differential questionnaire of depression (DDF and Questionnaire of anxiety (STAI X1. Our data showed autogenic training program significant improved depressions symptoms and anxiety in experimental research group (p ≤ 0.05, however there was no main change of depression symptoms and anxiety values for control group (p = n.s..

  13. The Heritability of Prostate Cancer in the Nordic Twin Study of Cancer

    DEFF Research Database (Denmark)

    von Bornemann Hjelmborg, Jacob; Scheike, Thomas; Holst, Klaus

    2014-01-01

    Background: Prostate cancer is thought to be the most heritable cancer, although little is known about how this genetic contribution varies across age. Methods: To address this question, we undertook the world’s largest prospective study in the Nordic Twin Study of Cancer cohort, including 18...... risk and liability. Results: The cumulative risk of prostate cancer was similar to that of the background population. The cumulative risk for twins whose co-twin was diagnosed with prostate cancer was greater for MZ than for DZ twins across all ages. Among concordantly affected pairs, the time between...... diagnoses was significantly shorter for MZ than DZ pairs (median 3.8 versus 6.5 years, respectively). Genetic differences contributed substantially to variation in both the risk and the liability (heritability=58% (95% CI 52%–63%) of developing prostate cancer. The relative contribution of genetic factors...

  14. Oxidative Stress and DNA Methylation in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Krishna Vanaja Donkena

    2010-01-01

    Full Text Available The protective effects of fruits, vegetables, and other foods on prostate cancer may be due to their antioxidant properties. An imbalance in the oxidative stress/antioxidant status is observed in prostate cancer patients. Genome oxidative damage in prostate cancer patients is associated with higher lipid peroxidation and lower antioxidant levels. Oxygen radicals are associated with different steps of carcinogenesis, including structural DNA damage, epigenetic changes, and protein and lipid alterations. Epigenetics affects genetic regulation, cellular differentiation, embryology, aging, cancer, and other diseases. DNA methylation is perhaps the most extensively studied epigenetic modification, which plays an important role in the regulation of gene expression and chromatin architecture, in association with histone modification and other chromatin-associated proteins. This review will provide a broad overview of the interplay of oxidative stress and DNA methylation, DNA methylation changes in regulation of gene expression, lifestyle changes for prostate cancer prevention, DNA methylation as biomarkers for prostate cancer, methods for detection of methylation, and clinical application of DNA methylation inhibitors for epigenetic therapy.

  15. Circulating Tumor Cells in Prostate Cancer

    International Nuclear Information System (INIS)

    Hu, Brian; Rochefort, Holly; Goldkorn, Amir

    2013-01-01

    Circulating tumor cells (CTCs) can provide a non-invasive, repeatable snapshot of an individual patient’s tumor. In prostate cancer, CTC enumeration has been extensively studied and validated as a prognostic tool and has received FDA clearance for use in monitoring advanced disease. More recently, CTC analysis has been shifting from enumeration to more sophisticated molecular characterization of captured cells, which serve as a “liquid biopsy” of the tumor, reflecting molecular changes in an individual’s malignancy over time. Here we will review the main CTC studies in advanced and localized prostate cancer, highlighting the important gains as well as the challenges posed by various approaches, and their implications for advancing prostate cancer management

  16. The Relationship between Androgenic Alopecia and Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Ghasem Rahmatpour Rokni

    2016-07-01

    Full Text Available Prostate cancer (PC and Androgenic Alopecia (AGA i are both common diseases in elder men. It seems that androgen plays a crucial role in the growth and development of prostate cancer. Therefore, the current study intended to investigate the relationship between androgenic alopecia and prostate cancer. The present study is a case-control study conducted on 75 patients with prostate cancer (case group referring to Imam Khomeini Hospital in Sari, Iran. The case group was compared with the control group (75 healthy individuals. The intended questionnaire of the study included information such as the age, sex, duration of disease, stage of disease, level of PSA, time diagnosis and time of interview for all the participants. The results of interview and clinical examination along with the patient’s information all were filled in the questionnaire and were statistically analyzed by SPSS after data collection. The mean age of PC group and healthy group was respectively 69.08 ± 8.97 and 68 .45 ± 10.16 years. The average level of PSA was 10.86 ± 11.7 and 2.66 ± 2.7 ng/ml in PC and healthy group in turn. The average duration of cancer was 12.63 ± 9.19 months in PC group. Furthermore, about 6.7% of cancer patients were in stage I, 48% were stage II, 29.3% were in stage III and 16% were in stage IV of prostate cancer. Besides, the number of cancer patients who had both frontal and vertex alopecia (baldness altogether exceeded healthy individuals (P=0.002. According to the results of the present study, there was a significant relationship between prostate cancer and androgenic alopecia which might have been caused by the effect of androgens on both diseases. Consequently, androgenic alopecia can be considered as one of the risk factors associated with prostate cancer.

  17. Body mass index in relation to serum prostate-specific antigen levels and prostate cancer risk.

    Science.gov (United States)

    Bonn, Stephanie E; Sjölander, Arvid; Tillander, Annika; Wiklund, Fredrik; Grönberg, Henrik; Bälter, Katarina

    2016-07-01

    High Body mass index (BMI) has been directly associated with risk of aggressive or fatal prostate cancer. One possible explanation may be an effect of BMI on serum levels of prostate-specific antigen (PSA). To study the association between BMI and serum PSA as well as prostate cancer risk, a large cohort of men without prostate cancer at baseline was followed prospectively for prostate cancer diagnoses until 2015. Serum PSA and BMI were assessed among 15,827 men at baseline in 2010-2012. During follow-up, 735 men were diagnosed with prostate cancer with 282 (38.4%) classified as high-grade cancers. Multivariable linear regression models and natural cubic linear regression splines were fitted for analyses of BMI and log-PSA. For risk analysis, Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) and natural cubic Cox regression splines producing standardized cancer-free probabilities were fitted. Results showed that baseline Serum PSA decreased by 1.6% (95% CI: -2.1 to -1.1) with every one unit increase in BMI. Statistically significant decreases of 3.7, 11.7 and 32.3% were seen for increasing BMI-categories of 25 prostate cancer risk although results were indicative of a positive association to incidence rates of high-grade disease and an inverse association to incidence of low-grade disease. However, findings regarding risk are limited by the short follow-up time. In conclusion, BMI was inversely associated to PSA-levels. BMI should be taken into consideration when referring men to a prostate biopsy based on serum PSA-levels. © 2016 UICC.

  18. Androgen receptor profiling predicts prostate cancer outcome

    NARCIS (Netherlands)

    S. Stelloo (Suzan); E. Nevedomskaya (Ekaterina); H.G. van der Poel (Henk G.); J. de Jong (Jeroen); G.J.H.L. Leenders (Geert); G.W. Jenster (Guido); L. Wessels (Lodewyk); A.M. Bergman (Andries); W. Zwart (Wilbert)

    2015-01-01

    textabstractProstate cancer is the second most prevalent malignancy in men. Biomarkers for outcome prediction are urgently needed, so that high-risk patients could be monitored more closely postoperatively. To identify prognostic markers and to determine causal players in prostate cancer

  19. Prostate Specific Membrane Antigen (PSMA) Targeted Bio-orthogonal Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    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