Sample records for abrogates prostate cancer

  1. Making Aggressive Prostate Cancer Quiescent by Abrogating Cholesterol Esterification

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0557 TITLE: Making Aggressive Prostate Cancer Quiescent by Abrogating Cholesterol Esterification PRINCIPAL...Aggressive Prostate Cancer Quiescent by Abrogating Cholesterol Esterification 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0557 5c. PROGRAM...application is to establish the viability of a new strategy of treating late stage PCa through therapeutic targeting of cholesterol metabolism in vivo

  2. Making Aggressive Prostate Cancer Quiescent by Abrogating Cholesterol Esterification

    DTIC Science & Technology

    2017-10-01

    and prostate cancer biology (Dr. T. Ratliff, co-PI). 15. SUBJECT TERMS- 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES...X. Liu, co-PI), and prostate cancer biology (Dr. T. Ratliff, co-PI). 2. KEYWORDS: Prostate cancer, lipid droplet, metabolism, cholesterol...presentations: 10 09-09-2016, “Lipid metabolism: from single cell biology to in vivo diagnosis”, Big Ten Cancer Research Consortium Summit, Indianapolis

  3. Carbidopa abrogates L-dopa decarboxylase coactivation of the androgen receptor and delays prostate tumor progression.

    PubMed

    Wafa, Latif A; Cheng, Helen; Plaa, Nathan; Ghaidi, Fariba; Fukumoto, Takahiro; Fazli, Ladan; Gleave, Martin E; Cox, Michael E; Rennie, Paul S

    2012-06-15

    The androgen receptor (AR) plays a central role in prostate cancer progression to the castration-resistant (CR) lethal state. L-Dopa decarboxylase (DDC) is an AR coactivator that increases in expression with disease progression and is coexpressed with the receptor in prostate adenocarcinoma cells, where it may enhance AR activity. Here, we hypothesize that the DDC enzymatic inhibitor, carbidopa, can suppress DDC-coactivation of AR and retard prostate tumor growth. Treating LNCaP prostate cancer cells with carbidopa in transcriptional assays suppressed the enhanced AR transactivation seen with DDC overexpression and decreased prostate-specific antigen (PSA) mRNA levels. Carbidopa dose-dependently inhibited cell growth and decreased survival in LNCaP cell proliferation and apoptosis assays. The inhibitory effect of carbidopa on DDC-coactivation of AR and cell growth/survival was also observed in PC3 prostate cancer cells (stably expressing AR). In vivo studies demonstrated that serum PSA velocity and tumor growth rates elevated ∼2-fold in LNCaP xenografts, inducibly overexpressing DDC, were reverted to control levels with carbidopa administration. In castrated mice, treating LNCaP tumors, expressing endogenous DDC, with carbidopa delayed progression to the CR state from 6 to 10 weeks, while serum PSA and tumor growth decreased 4.3-fold and 5.4-fold, respectively. Our study is a first time demonstration that carbidopa can abrogate DDC-coactivation of AR in prostate cancer cells and tumors, decrease serum PSA, reduce tumor growth and delay CR progression. Since carbidopa is clinically approved, it may be readily used as a novel therapeutic strategy to suppress aberrant AR activity and delay prostate cancer progression. Copyright © 2011 UICC.

  4. Cell intrinsic abrogation of TGFβ signaling delays but does not prevent dysfunction of self/tumor specific CD8 T cells in a murine model of autochthonous prostate cancer

    PubMed Central

    Chou, Cassie K.; Schietinger, Andrea; Liggitt, H. Denny; Tan, Xiaoxia; Funk, Sarah; Freeman, Gordon J.; Ratliff, Timothy L.; Greenberg, Norman M.; Greenberg, Philip D.

    2012-01-01

    Adoptive T cell therapy (ACT) for the treatment of established cancers is actively being pursued in clinical trials. However, poor in vivo persistence and maintenance of anti-tumor activity of transferred T cells remain major problems. Transforming growth factor beta (TGFβ) is a potent immunosuppressive cytokine that is often expressed at high levels within the tumor microenvironment, potentially limiting T cell mediated anti-tumor activity. Here, we used a model of autochthonous murine prostate cancer to evaluate the effect of cell intrinsic abrogation of TGFβ signaling in self/tumor specific CD8 T cells used in ACT to target the tumor in situ. We found that persistence and anti-tumor activity of adoptively transferred effector T cells deficient in TGFβ signaling was significantly improved in the cancerous prostate. However, over time, despite persistence in peripheral lymphoid organs, the numbers of transferred cells in the prostate decreased and the residual prostate infiltrating T cells were no longer functional. These findings reveal that TGFβ negatively regulates the accumulation and effector function of transferred self/tumor specific CD8 T cells and highlight that, when targeting a tumor antigen that is also expressed as a self-protein, additional substantive obstacles are operative within the tumor microenvironment, potentially hampering the success of ACT for solid tumors. PMID:22984076

  5. PKCε Is an Essential Mediator of Prostate Cancer Bone Metastasis.

    PubMed

    Gutierrez-Uzquiza, Alvaro; Lopez-Haber, Cynthia; Jernigan, Danielle L; Fatatis, Alessandro; Kazanietz, Marcelo G

    2015-09-01

    The bone is a preferred site for metastatic homing of prostate cancer cells. Once prostate cancer patients develop skeletal metastases, they eventually succumb to the disease; therefore, it is imperative to identify key molecular drivers of this process. This study examines the involvement of protein kinase C epsilon (PKCε), an oncogenic protein that is abnormally overexpressed in human tumor specimens and cell lines, on prostate cancer cell bone metastasis. PC3-ML cells, a highly invasive prostate cancer PC3 derivative with bone metastatic colonization properties, failed to induce skeletal metastatic foci upon inoculation into nude mice when PKCε expression was silenced using shRNA. Interestingly, while PKCε depletion had only marginal effects on the proliferative, adhesive, and migratory capacities of PC3-ML cells in vitro or in the growth of xenografts upon s.c. inoculation, it caused a significant reduction in cell invasiveness. Notably, PKCε was required for transendothelial cell migration (TEM) as well as for the growth of PC3-ML cells in a bone biomimetic environment. At a mechanistic level, PKCε depletion abrogates the expression of IL1β, a cytokine implicated in skeletal metastasis. Taken together, PKCε is a key factor for driving the formation of bone metastasis by prostate cancer cells and is a potential therapeutic target for advanced stages of the disease. This study uncovers an important new function of PKCε in the dissemination of cancer cells to the bone; thus, highlighting the promising potential of this oncogenic kinase as a therapeutic target for skeletal metastasis. ©2015 American Association for Cancer Research.

  6. Prostate cancer - resources

    MedlinePlus

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

  7. Prostate cancer screening

    MedlinePlus

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

  8. The pepper's natural ingredient capsaicin induces autophagy blockage in prostate cancer cells

    PubMed Central

    Ramos-Torres, Ágata; Bort, Alicia; Morell, Cecilia; Rodríguez-Henche, Nieves; Díaz-Laviada, Inés

    2016-01-01

    Capsaicin, the pungent ingredient of red hot chili peepers, has been shown to have anti-cancer activities in several cancer cells, including prostate cancer. Several molecular mechanisms have been proposed on its chemopreventive action, including ceramide accumulation, endoplasmic reticulum stress induction and NFκB inhibition. However, the precise mechanisms by which capsaicin exerts its anti-proliferative effect in prostate cancer cells remain questionable. Herein, we have tested the involvement of autophagy on the capsaicin mechanism of action on prostate cancer LNCaP and PC-3 cells. The results showed that capsaicin induced prostate cancer cell death in a time- and concentration-dependent manner, increased the levels of microtubule-associated protein light chain 3-II (LC3-II, a marker of autophagy) and the accumulation of the cargo protein p62 suggesting an autophagy blockage. Moreover, confocal microscopy revealed that capsaicin treatment increased lysosomes which co-localized with LC3 positive vesicles in a similar extent to that produced by the lysosomal protease inhibitors E64 and pepstatin pointing to an autophagolysosomes breakdown inhibition. Furthermore, we found that capsaicin triggered ROS generation in cells, while the levels of ROS decreased with N-acetyl-cysteine (NAC), a ROS scavenger. Co-treatment of cells with NAC and capsaicin abrogated the effects of capsaicin on autophagy and cell death. Normal prostate PNT2 and RWPE-1 cells were more resistant to capsaicin-induced cytotoxicity and did not accumulate p62 protein. Taken together, these results suggest that ROS-mediated capsaicin-induced autophagy blockage contributes to antiproliferation in prostate cancer cells, which provides new insights into the anticancer molecular mechanism of capsaicin. PMID:26625315

  9. MicroRNA-613 represses prostate cancer cell proliferation and invasion through targeting Frizzled7

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

    Ren, Wei; Department of Urology, Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710068; Li, Chan

    A growing number of studies have indicated that microRNAs (miRNAs) are critical regulators of carcinogenesis and cancer progression and may serve as potential therapeutic tools for cancer therapy. Frizzled7 (Fzd7), the most important receptor of the Wnt signaling pathway, is extensively involved in cancer development and progression. However, the role of Fzd7 in prostate cancer remains unclear. In this study, we aimed to explore the expression of Fzd7 in prostate cancer and test whether modulating Fzd7 expression by miR-613 would have an impact on prostate cancer cell proliferation and invasion. We found that Fzd7 was highly expressed in prostate cancermore » cell lines. Through bioinformatics analysis, Fzd7 was predicted as a target gene of miR-613, which was validated by dual-luciferase reporter assays, real-time quantitative polymerase chain reaction and Western blot analysis. By gain of function experiments, we showed that overexpression of miR-613 significantly suppressed prostate cancer cell proliferation and invasion. Furthermore, miR-613 overexpression markedly downregulated the Wnt signaling pathway. Through a rescue experiment, we showed that overexpression of Fzd7 could abrogate the inhibitory effect of miR-613 on cell proliferation and invasion as well as Wnt signaling. Additionally, these results were further strengthened by data showing that miR-613 was significantly downregulated in prostate cancer tissues, exhibiting an inverse correlation with Fzd7 expression. In conclusion, our study suggests that miR-613 functions as a tumor suppressor, partially through targeting Fzd7, and is a potential therapeutic target for prostate cancer. - Highlights: • Fzd7 was highly expressed in prostate cancer. • Fzd7 was predicted as a target gene of miR-613. • MiR-613 negatively regulated prostate cancer by Fzd7. • MiR-613 inversely correlated with Fzd7 in prostate cancer.« less

  10. Pathogenesis of prostate cancer and hormone refractory prostate cancer

    PubMed Central

    Girling, J. S.; Whitaker, H. C.; Mills, I. G.; Neal, D. E.

    2007-01-01

    Prostate cancer is the second most common malignancy in males and the leading cause of cancer death. Prostate cancer is initially androgen dependent and relies upon the androgen receptor (AR) to mediate the effects of androgens. The AR is also the target for therapy using antiandrogens and LHRH analogues. However, all cancers eventually become androgen independent, often referred to as hormone refractory prostate cancer. The processes involved in this transformation are yet to be fully understood but research in this area has discovered numerous potential mechanisms including AR amplification, over-expression or mutation and alterations in the AR signaling pathway. This review of the recent literature examines the current knowledge and developments in the understanding of the molecular biology of prostate cancer and hormone refractory prostate cancer, summarizing the well characterized pathways involved as well as introducing new concepts that may offer future solutions to this difficult problem. PMID:19675761

  11. Prostate Cancer

    MedlinePlus

    ... breast cancer (BRCA1 or BRCA2) or a very strong family history of breast cancer, your risk of prostate cancer may be higher. Obesity. Obese men diagnosed with prostate cancer may be more likely ...

  12. 6 Common Cancers - Prostate Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Prostate Cancer Past Issues / Spring 2007 Table of Contents For ... early screening. Photo: AP Photo/Danny Moloshok Prostate Cancer The prostate gland is a walnut-sized structure ...

  13. The microbiome in prostate inflammation and prostate cancer.

    PubMed

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

    2018-05-23

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

  14. Genetics Home Reference: prostate cancer

    MedlinePlus

    ... prostate cancer Genetic Testing Registry: Prostate cancer aggressiveness quantitative trait locus on chromosome 19 Genetic Testing Registry: ... OMIM (25 links) PROSTATE CANCER PROSTATE CANCER AGGRESSIVENESS QUANTITATIVE TRAIT LOCUS ON CHROMOSOME 19 PROSTATE CANCER ANTIGEN ...

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

    PubMed Central

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

    2013-01-01

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

  16. Copper as a target for prostate cancer therapeutics: copper-ionophore pharmacology and altering systemic copper distribution.

    PubMed

    Denoyer, Delphine; Pearson, Helen B; Clatworthy, Sharnel A S; Smith, Zoe M; Francis, Paul S; Llanos, Roxana M; Volitakis, Irene; Phillips, Wayne A; Meggyesy, Peter M; Masaldan, Shashank; Cater, Michael A

    2016-06-14

    Copper-ionophores that elevate intracellular bioavailable copper display significant therapeutic utility against prostate cancer cells in vitro and in TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice. However, the pharmacological basis for their anticancer activity remains unclear, despite impending clinical trails. Herein we show that intracellular copper levels in prostate cancer, evaluated in vitro and across disease progression in TRAMP mice, were not correlative with copper-ionophore activity and mirrored the normal levels observed in patient prostatectomy tissues (Gleason Score 7 & 9). TRAMP adenocarcinoma cells harbored markedly elevated oxidative stress and diminished glutathione (GSH)-mediated antioxidant capacity, which together conferred selective sensitivity to prooxidant ionophoric copper. Copper-ionophore treatments [CuII(gtsm), disulfiram & clioquinol] generated toxic levels of reactive oxygen species (ROS) in TRAMP adenocarcinoma cells, but not in normal mouse prostate epithelial cells (PrECs). Our results provide a basis for the pharmacological activity of copper-ionophores and suggest they are amendable for treatment of patients with prostate cancer. Additionally, recent in vitro and mouse xenograft studies have suggested an increased copper requirement by prostate cancer cells. We demonstrated that prostate adenocarcinoma development in TRAMP mice requires a functional supply of copper and is significantly impeded by altered systemic copper distribution. The presence of a mutant copper-transporting Atp7b protein (tx mutation: A4066G/Met1356Val) in TRAMP mice changed copper-integration into serum and caused a remarkable reduction in prostate cancer burden (64% reduction) and disease severity (grade), abrogating adenocarcinoma development. Implications for current clinical trials are discussed.

  17. Copper as a target for prostate cancer therapeutics: copper-ionophore pharmacology and altering systemic copper distribution

    PubMed Central

    Denoyer, Delphine; Pearson, Helen B.; Clatworthy, Sharnel A.S.; Smith, Zoe M.; Francis, Paul S.; Llanos, Roxana M.; Volitakis, Irene; Phillips, Wayne A.; Meggyesy, Peter M.; Masaldan, Shashank; Cater, Michael A.

    2016-01-01

    Copper-ionophores that elevate intracellular bioavailable copper display significant therapeutic utility against prostate cancer cells in vitro and in TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice. However, the pharmacological basis for their anticancer activity remains unclear, despite impending clinical trails. Herein we show that intracellular copper levels in prostate cancer, evaluated in vitro and across disease progression in TRAMP mice, were not correlative with copper-ionophore activity and mirrored the normal levels observed in patient prostatectomy tissues (Gleason Score 7 & 9). TRAMP adenocarcinoma cells harbored markedly elevated oxidative stress and diminished glutathione (GSH)-mediated antioxidant capacity, which together conferred selective sensitivity to prooxidant ionophoric copper. Copper-ionophore treatments [CuII(gtsm), disulfiram & clioquinol] generated toxic levels of reactive oxygen species (ROS) in TRAMP adenocarcinoma cells, but not in normal mouse prostate epithelial cells (PrECs). Our results provide a basis for the pharmacological activity of copper-ionophores and suggest they are amendable for treatment of patients with prostate cancer. Additionally, recent in vitro and mouse xenograft studies have suggested an increased copper requirement by prostate cancer cells. We demonstrated that prostate adenocarcinoma development in TRAMP mice requires a functional supply of copper and is significantly impeded by altered systemic copper distribution. The presence of a mutant copper-transporting Atp7b protein (tx mutation: A4066G/Met1356Val) in TRAMP mice changed copper-integration into serum and caused a remarkable reduction in prostate cancer burden (64% reduction) and disease severity (grade), abrogating adenocarcinoma development. Implications for current clinical trials are discussed. PMID:27175597

  18. Prostate Cancer Ambassadors

    PubMed Central

    Vines, Anissa I.; Hunter, Jaimie C.; Carlisle, Veronica A.; Richmond, Alan N.

    2016-01-01

    African American men bear a higher burden of prostate cancer than Caucasian men, but knowledge about how to make an informed decision about prostate cancer screening is limited. A lay health advisor model was used to train “Prostate Cancer Ambassadors” on prostate cancer risk and symptoms, how to make an informed decision for prostate-specific antigen screening, and how to deliver the information to members of their community. Training consisted of two, 6-hour interactive sessions and was implemented in three predominantly African American communities over an 8-month period between 2013 and 2014. Following training, Ambassadors committed to contacting at least 10 people within 3 months using a toolkit composed of wallet-sized informational cards for distribution, a slide presentation, and a flip chart. Thirty-two Ambassadors were trained, with more than half being females (59%) and half reporting a family history of prostate cancer. Prostate cancer knowledge improved significantly among Ambassadors (p ≤ .0001). Self-efficacy improved significantly for performing outreach tasks (p < .0001), and among women in helping a loved one with making an informed decision (p = .005). There was also an improvement in collective efficacy in team members (p = .0003). Twenty-nine of the Ambassadors fulfilled their commitment to reach at least 10 people (average number of contacts per Ambassador was 11). In total, 355 individuals were reached with the prostate cancer information. The Ambassador training program proved successful in training Ambassadors to reach communities about prostate cancer and how to make an informed decision about screening. PMID:27099348

  19. Prostate Cancer

    MedlinePlus

    ... man's bladder that produces fluid for semen. Prostate cancer is common among older men. It is rare ... younger than 40. Risk factors for developing prostate cancer include being over 65 years of age, family ...

  20. Prostate Cancer Epigenome

    PubMed Central

    Chinaranagari, Swathi; Sharma, Pankaj; Bowen, Nathan J.; Chaudhary, Jaideep

    2018-01-01

    Prostate cancer is a major health burden within the ever-increasingly aging US population. The molecular mechanisms involved in prostate cancer are diverse and heterogeneous. In this context, epigenetic changes, both global and gene specific, are now an emerging alternate mechanism in disease initiation and progression. The three major risk factors in prostate cancer: age, geographic ancestry, and environment are all influenced by epigenetics and additional significant insight is required to gain an understanding of the underlying mechanisms. The androgen receptor and its downstream effector pathways, central to prostate cancer initiation and progression, are subject to a multitude of epigenetic alterations. In this review we focus on the global perspective of epigenetics and the use of recent next-generation sequencing platforms to interrogate epigenetic changes in the prostate cancer genome. PMID:25421658

  1. Prostate cancer epigenome.

    PubMed

    Chinaranagari, Swathi; Sharma, Pankaj; Bowen, Nathan J; Chaudhary, Jaideep

    2015-01-01

    Prostate cancer is a major health burden within the ever-increasingly aging US population. The molecular mechanisms involved in prostate cancer are diverse and heterogeneous. In this context, epigenetic changes, both global and gene specific, are now an emerging alternate mechanism in disease initiation and progression. The three major risk factors in prostate cancer: age, geographic ancestry, and environment are all influenced by epigenetics and additional significant insight is required to gain an understanding of the underlying mechanisms. The androgen receptor and its downstream effector pathways, central to prostate cancer initiation and progression, are subject to a multitude of epigenetic alterations. In this review we focus on the global perspective of epigenetics and the use of recent next-generation sequencing platforms to interrogate epigenetic changes in the prostate cancer genome.

  2. Prostate cancer

    MedlinePlus

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

  3. Treating Localized Prostate Cancer

    MedlinePlus

    ... Prostate Cancer: Update of a 2008 Systematic Review . Comparative Effectiveness Review No. 146. (Prepared by the ECRI ... Prostate Cancer Research Protocol Archived March 29, 2013 Comparative Effectiveness of Therapies for Clinically Localized Prostate Cancer: ...

  4. Screening for prostate cancer

    NASA Technical Reports Server (NTRS)

    Weirich, Stephen A.

    1993-01-01

    Despite recent advances in both the survival and cure rates for many forms of cancer, unfortunately the same has not been true for prostate cancer. In fact, the age-adjusted death rate from prostate cancer has not significantly improved since 1949, and prostate cancer remains the most common cancer in American men, causing the second highest cancer mortality rate. Topics discussed include the following: serum testosterone levels; diagnosis; mortality statistics; prostate-sppecific antigen (PSA) tests; and the Occupational Medicine Services policy at LeRC.

  5. Immunotherapy for Prostate Cancer: Where Do We Go From Here?-PART 2: Checkpoint Inhibitors, Immunotherapy Combinations, Tumor Microenvironment Modulation, and Cellular Therapies.

    PubMed

    Patel, Amar; Fong, Lawrence

    2018-06-15

    Therapeutic approaches that harness the power of the immune system to eliminate cancer cells have produced a paradigm shift in the management of a variety of malignancies. Prostate cancer has been a particularly active area of investigation in cancer immunotherapy, with significant laboratory and clinical evidence suggesting that this disease can be a viable target for cytotoxic immune cells. In the first article of this series, we discussed the diverse vaccination approaches that have been employed to prime native antigen-specific responses against prostate cancer, highlighting successes such as sipuleucel-T, as well as the significant challenges that remain. Here we focus on alternative methods of harnessing both adaptive and innate antitumor immunity to target prostate cancer cells. Approaches that enhance the activation of T cells, modulation of the tumor microenvironment to abrogate its inherent immunosuppressive mechanisms, and engineering of antigen-specific antibody and cellular products to target tumor cells will be discussed. We will then look ahead to provide a perspective on how this growing collection of immunotherapeutic approaches may ultimately be combined to target prostate cancer from a variety of angles.

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

    PubMed

    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.

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

    PubMed Central

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

    2015-01-01

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

  8. Benign Prostatic Hyperplasia and the Risk of Prostate Cancer and Bladder Cancer

    PubMed Central

    Dai, Xiaoyu; Fang, Xiangming; Ma, Ying; Xianyu, Jianbo

    2016-01-01

    Abstract Benign prostatic hyperplasia (BPH) has been suggested to be a risk factor for certain urologic cancers, but the current evidence is inconsistent. The aim of this study was to investigate the association between BPH and urologic cancers. MEDLINE, EMBASE, Cochrane Library, and Web of Science were searched for potential eligible studies. We included case-control studies or cohort studies, which evaluated the association between BPH and urologic cancers (including prostate cancer, bladder cancer, kidney cancer, testicular cancer, or penile cancer). Overall effect estimates were calculated using the DerSimonian–Laird method for a random-effects model. Summary effect-size was calculated as risk ratio (RR), together with the 95% confidence interval (CI). This systematic review included 16 case-control studies and 10 cohort studies evaluating the association of BPH and prostate or bladder cancer; we did not identify any study about other urologic cancers. Meta-analyses demonstrated that BPH was associated with an increased incidence of prostate cancer (case-control study: RR = 3.93, 95% CI = 2.18–7.08; cohort-study: RR = 1.41, 95% CI = 1.00–1.99) and bladder cancer (case-control study: RR = 2.50, 95% CI = 1.63–3.84; cohort-study: RR = 1.58, 95% CI = 1.28–1.95). Subgroup analysis by ethnicity suggested that the association between BPH and prostate cancer was much stronger in Asians (RR = 6.09, 95% CI = 2.96–12.54) than in Caucasians (RR = 1.54, 95% CI = 1.19–2.01). Egger's tests indicated low risk of publication bias (prostate cancer: P = 0.11; bladder cancer: P = 0.95). BPH is associated with an increased risk of prostate cancer and bladder cancer. The risk of prostate cancer is particularly high in Asian BPH patients. Given the limitations of included studies, additional prospective studies with strict design are needed to confirm our findings. PMID:27149447

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

    PubMed

    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.

  10. [Epigenetics of prostate cancer].

    PubMed

    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.

  11. Prostate Cancer Screening

    MedlinePlus

    ... decrease the risk of dying from cancer. Scientists study screening tests to find those with the fewest risks and ... or routine screening test for prostate cancer. Screening tests for prostate cancer are under study, and there are screening clinical trials taking place ...

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

    PubMed Central

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

    2010-01-01

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

  13. Digoxin and prostate cancer survival in the Finnish Randomized Study of Screening for Prostate Cancer.

    PubMed

    Kaapu, Kalle J; Murtola, Teemu J; Talala, Kirsi; Taari, Kimmo; Tammela, Teuvo Lj; Auvinen, Anssi

    2016-11-22

    Protective effects have been suggested for digoxin against prostate cancer risk. However, few studies have evaluated the possible effects on prostate cancer-specific survival. We studied the association between use of digoxin or beta-blocker sotalol and prostate cancer-specific survival as compared with users of other antiarrhythmic drugs in a retrospective cohort study. Our study population consisted of 6537 prostate cancer cases from the Finnish Randomized Study of Screening for Prostate Cancer diagnosed during 1996-2009 (485 digoxin users). The median exposure for digoxin was 480 DDDs (interquartile range 100-1400 DDDs). During a median follow-up of 7.5 years after diagnosis, 617 men (48 digoxin users) died of prostate cancer. We collected information on antiarrhythmic drug purchases from the national prescription database. Both prediagnostic and postdiagnostic drug usages were analysed using the Cox regression method. No association was found for prostate cancer death with digoxin usage before (HR 1.00, 95% CI 0.56-1.80) or after (HR 0.81, 95% CI 0.43-1.51) prostate cancer diagnosis. The results were also comparable for sotalol and antiarrhythmic drugs in general. Among men not receiving hormonal therapy, prediagnostic digoxin usage was associated with prolonged prostate cancer survival (HR 0.20, 95% CI 0.05-0.86). No general protective effects against prostate cancer were observed for digoxin or sotalol usage.

  14. Making Aggressive Prostate Cancer Quiescent by Abrogating Cholesterol Esterification

    DTIC Science & Technology

    2016-10-01

    team has been assembled , with expertise in spectroscopic imaging & nanomedicine (Dr. J. X. Cheng, PI), biochemistry (Dr. X. Liu, co-PI), and prostate...was approved in 2004 as the first- line cytotoxic chemotherapy owing to a modest increase in overall survival compared to mitoxantrone. Since 2010...interdisciplinary research team has been assembled , with expertise in spectroscopic imaging & nanomedicine (Dr. J. X. Cheng, PI), biochemistry (Dr. X. Liu, co-PI

  15. Insulin-like growth factor-I induces CLU expression through Twist1 to promote prostate cancer growth.

    PubMed

    Takeuchi, Ario; Shiota, Masaki; Beraldi, Eliana; Thaper, Daksh; Takahara, Kiyoshi; Ibuki, Naokazu; Pollak, Michael; Cox, Michael E; Naito, Seiji; Gleave, Martin E; Zoubeidi, Amina

    2014-03-25

    Clusterin (CLU) is cytoprotective molecular chaperone that is highly expressed in castrate-resistant prostate cancer (CRPC). CRPC is also characterized by increased insulin-like growth factor (IGF)-I responsiveness which induces prostate cancer survival and CLU expression. However, how IGF-I induces CLU expression and whether CLU is required for IGF-mediated growth signaling remain unknown. Here we show that IGF-I induced CLU via STAT3-Twist1 signaling pathway. In response to IGF-I, STAT3 was phosphorylated, translocated to the nucleus and bound to the Twist1 promoter to activate Twist1 transcription. In turn, Twist1 bound to E-boxes on the CLU promoter and activated CLU transcription. Inversely, we demonstrated that knocking down Twist1 abrogated IGF-I induced CLU expression, indicating that Twist1 mediated IGF-I-induced CLU expression. When PTEN knockout mice were crossed with lit/lit mice, the resultant IGF-I deficiency suppressed Twist1 as well as CLU gene expression in mouse prostate glands. Moreover, both Twist1 and CLU knockdown suppressed prostate cancer growth accelerated by IGF-I, suggesting the relevance of this signaling not only in an in vitro, but also in an in vivo. Collectively, this study indicates that IGF-I induces CLU expression through sequential activation of STAT3 and Twist1, and suggests that this signaling cascade plays a critical role in prostate cancer pathogenesis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Quantitative Proteomic Profiling of Prostate Cancer Reveals a Role for miR-128 in Prostate Cancer*

    PubMed Central

    Khan, Amjad P.; Poisson, Laila M.; Bhat, Vadiraja B.; Fermin, Damian; Zhao, Rong; Kalyana-Sundaram, Shanker; Michailidis, George; Nesvizhskii, Alexey I.; Omenn, Gilbert S.; Chinnaiyan, Arul M.; Sreekumar, Arun

    2010-01-01

    Multiple, complex molecular events characterize cancer development and progression. Deciphering the molecular networks that distinguish organ-confined disease from metastatic disease may lead to the identification of biomarkers of cancer invasion and disease aggressiveness. Although alterations in gene expression have been extensively quantified during neoplastic progression, complementary analyses of proteomic changes have been limited. Here we interrogate the proteomic alterations in a cohort of 15 prostate-derived tissues that included five each from adjacent benign prostate, clinically localized prostate cancer, and metastatic disease from distant sites. The experimental strategy couples isobaric tags for relative and absolute quantitation with multidimensional liquid phase peptide fractionation followed by tandem mass spectrometry. Over 1000 proteins were quantified across the specimens and delineated into clinically localized and metastatic prostate cancer-specific signatures. Included in these class-specific profiles were both proteins that were known to be dysregulated during prostate cancer progression and new ones defined by this study. Enrichment analysis of the prostate cancer-specific proteomic signature, to gain insight into the functional consequences of these alterations, revealed involvement of miR-128-a/b regulation during prostate cancer progression. This finding was validated using real time PCR analysis for microRNA transcript levels in an independent set of 15 clinical specimens. miR-128 levels were elevated in benign prostate epithelial cell lines compared with invasive prostate cancer cells. Knockdown of miR-128 induced invasion in benign prostate epithelial cells, whereas its overexpression attenuated invasion in prostate cancer cells. Taken together, our profiles of the proteomic alterations of prostate cancer progression revealed miR-128 as a potentially important negative regulator of prostate cancer cell invasion. PMID:19955085

  17. Epigenetics of prostate cancer.

    PubMed

    Li, Long-Cheng

    2007-05-01

    Prostate cancer is the most common type of cancer other than skin cancer and the second leading cause of cancer death in men in the United States. Its exact causes are unknown. Several risk factors have been associated with prostate cancer including age, race, family history and diet. Epigenetic mechanisms including DNA methylation and histone modifications are important means of gene regulation and play essential roles in diverse biological and disease processes. Recently, frequent epigenetic aberrations such as DNA hypo- and hypermethylation and altered histone acetylation and methylation have been observed in prostate cancer affecting the expression and function of a large array of genes, leading to tumorigenesis, tumor progression and metastasis. In this chapter, we examined the current literature regarding epigenetic changes in prostate cancer and discuss the clinical potential of cancer epigenetics for the diagnosis and treatment of this disease.

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

    PubMed

    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

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

    PubMed Central

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

    2015-01-01

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

  20. Epigenetic modifications in prostate cancer.

    PubMed

    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.

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

    PubMed

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

    2015-02-01

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

  2. Precision medicine for advanced prostate cancer.

    PubMed

    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.

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

    PubMed

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

    2017-01-01

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

  4. GPRC6A regulates prostate cancer progression

    PubMed Central

    Pi, Min; Quarles, L. Darryl

    2011-01-01

    BACKGROUND GPRC6A is a nutrient sensing GPCR that is activated in vitro by a variety of ligands, including amino acids, calcium, zinc, osteocalcin (OC) and testosterone. The association between nutritional factors and risk of prostate cancer, the finding of increased expression of OC in prostate cancer cells and the association between GPRC6A and risk of prostate cancer in Japanese men implicates a role of GPRC6A in prostate cancer. METHODS We examined if GPRC6A is expressed in human prostate cancer cell lines and used siRNA-mediated knockdown GPRC6A expression in prostate cancer cells to explore the function of GPRC6A in vitro. To assess the role GPRC6A in prostate cancer progression in vivo we intercrossed Gprc6a−/− mice onto the TRAMP mouse prostate cancer model. RESULTS GPRC6A transcripts were markedly increased in prostate cancer cell lines 22Rv1, PC-3 and LNCaP, compared to the normal prostate RWPE-1 cell line. In addition, a panel of GPRC6A ligands, including calcium, OC, and arginine, exhibited in prostate cancer cell lines a dose-dependent stimulation of ERK activity, cell proliferation, chemotaxis, and prostate specific antigen and Runx 2 gene expression. These responses were inhibited by siRNA-mediated knockdown of GPRC6A. Finally, transfer of Gprc6a deficiency onto a TRAMP mouse model of prostate cancer significantly retarded prostate cancer progression and improved survival of compound Gprc6a−/−/TRAMP mice. CONCLUSIONS GPRC6A is a novel molecular target for regulating prostate growth and cancer progression. Increments in GPRC6A may augment the ability of prostate cancer cells to proliferate in response to dietary and bone derived ligands. PMID:21681779

  5. Prostate cancer: cryotherapy.

    PubMed

    Shinohara, Katsuto

    2003-11-01

    The incidence of prostate cancer has more than doubled in the last 10 years, and 220,900 new cases will be detected in 2003. This increase is due in large part to increased use of prostate-specific antigen (PSA)-based screening, transrectal ultrasonography, and random biopsy of the prostate. The treatment of prostate cancer, however, remains controversial, and no consensus has been established as to what constitutes appropriate treatment for any stage of disease, especially for localized cancers. Radical prostatectomy, radiation therapy, or watchful waiting all have their advocates, and the risks and benefits of these approaches are discussed frequently. Skepticism about conventional treatments has stimulated patients and physicians to search for alternatives that are effective and associated with limited morbidity. Technologic developments have rekindled interest in cryotherapy as a viable alternative to other, more conventional localized therapies. Given the relative paucity of alternatives for patients who experience biochemical progression after radiotherapy, cryosurgery also may prove to be a good alternative for those patients whose tumors appear to remain localized despite progression. In addition, it appears that cryosurgery will play an increased role in the future management of prostate cancer.

  6. Biomarkers in localized prostate cancer

    PubMed Central

    Ferro, Matteo; Buonerba, Carlo; Terracciano, Daniela; Lucarelli, Giuseppe; Cosimato, Vincenzo; Bottero, Danilo; Deliu, Victor M; Ditonno, Pasquale; Perdonà, Sisto; Autorino, Riccardo; Coman, Ioman; De Placido, Sabino; Di Lorenzo, Giuseppe; De Cobelli, Ottavio

    2016-01-01

    Biomarkers can improve prostate cancer diagnosis and treatment. Accuracy of prostate-specific antigen (PSA) for early diagnosis of prostate cancer is not satisfactory, as it is an organ- but not cancer-specific biomarker, and it can be improved by using models that incorporate PSA along with other test results, such as prostate cancer antigen 3, the molecular forms of PSA (proPSA, benign PSA and intact PSA), as well as kallikreins. Recent reports suggest that new tools may be provided by metabolomic studies as shown by preliminary data on sarcosine. Additional molecular biomarkers have been identified by the use of genomics, proteomics and metabolomics. We review the most relevant biomarkers for early diagnosis and management of localized prostate cancer. PMID:26768791

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

    PubMed

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

    2017-07-01

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

  8. Epigenetic Regulation in Prostate Cancer Progression.

    PubMed

    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.

  9. Prostate cancer and inflammation: the evidence

    PubMed Central

    Sfanos, Karen S; De Marzo, Angelo M

    2014-01-01

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

  10. Prostate Cancer Ambassadors: Process and Outcomes of a Prostate Cancer Informed Decision-Making Training Program.

    PubMed

    Vines, Anissa I; Hunter, Jaimie C; Carlisle, Veronica A; Richmond, Alan N

    2016-04-19

    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. © The Author(s) 2016.

  11. Cholesterol and Prostate Cancer

    PubMed Central

    Pelton, Kristine; Freeman, Michael R.; Solomon, Keith R.

    2012-01-01

    Summary Prostate cancer risk can be modified by environmental factors, however the molecular mechanisms affecting susceptibility to this disease are not well understood. As a result of a series of recently published studies, the steroidal lipid, cholesterol, has emerged as a clinically relevant therapeutic target in prostate cancer. This review summarizes the findings from human studies as well as animal and cell biology models which suggest that high circulating cholesterol increases risk of aggressive prostate cancer, while cholesterol lowering strategies may confer protective benefit. Relevant molecular processes that have been experimentally tested and might explain these associations are described. We suggest that these promising results now could be applied prospectively to attempt to lower risk of prostate cancer in select populations. PMID:22824430

  12. A pituitary gene encodes a protein that produces differentiation of breast and prostate cancer cells.

    PubMed

    Platica, Micsunica; Ivan, Elena; Holland, James F; Ionescu, Alin; Chen, Sheryl; Mandeli, John; Unger, Pamela D; Platica, Ovidiu

    2004-02-10

    A cDNA clone of 1.1 kb encoding a 108-aa polypeptide was isolated from a human pituitary cDNA library by expression cloning. This protein was named tumor differentiation factor (TDF). The recombinant TDF protein and a 20-aa peptide, P1, selected from the ORF of the gene, induced morphological and biochemical changes consistent with differentiation of human breast and prostate cancer cells. Fibroblast, kidney, hepatoma, and leukemic lymphocytic cell lines were unaffected. Breast and prostate cancer cells aggregated in spheroid-like structures within 24 h of exposure to TDF. This effect was abrogated by a specific affinity-purified rabbit polyclonal anti-P1 Ab. E-cadherin expression was increased in a dose-dependent manner by TDF. Treatment of MCF7 cells with TDF led to production of a lactalbumin-related protein. Peptide P1 significantly decreased the growth of androgen-independent DU145 prostate cancer in severe combined immunodeficient mice. The presence of TDF protein in human sera was detected by the anti-P1 Ab, suggesting a role of TDF in endocrine metabolism. The fact that all activities of TDF can be mimicked by a peptide derived from the encoding TDF sequence opens the possibility of therapeutic applications.

  13. Precision medicine for advanced prostate cancer

    PubMed Central

    Mullane, Stephanie A.; Van Allen, Eliezer M.

    2016-01-01

    Purpose of review 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. Recent findings 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. Summary 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. PMID:26909474

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  16. Prostate Cancer in Deceased Liver Donors.

    PubMed

    Skalski, M; Gierej, B; Ziarkiewicz-Wróblewska, B; Hołówko, W; Krawczyk, M

    2016-06-01

    Prostate cancer is the second most common malignant tumor (13%) among male subjects in Poland. The aim of this study was to assess the prevalence of prostate cancer in a group of deceased liver donors. A total of 784 liver procurement attempts from deceased donors were performed in the Department of General, Transplant and Liver Surgery, Medical University of Warsaw, from January 1, 2012, to April 1, 2015; 700 grafts were actually used in a liver transplant. A retrospective analysis was performed based on these data. Among male donors (n = 486 [62%]), there were 30 (6.2%) cases of a frozen biopsy of the prostate performed before making the decision regarding liver graft utilization. In the group of 30 donors who underwent prostate examination, 3 (10%) were diagnosed as having prostate cancer of a moderate invasive stage. In 2 other cases, fresh frozen section suggested prostate cancer; however, this fact was not confirmed in routine section. liver transplantation was not performed in these cases of suspicion of prostate cancer (5 of 30 [17%]) in the frozen biopsy specimens. The difference between groups of donors with prostate cancer and benign pathology of the prostate gland according to prostate-specific antigen serum concentration (P = .578) or age (P = .730) was not statistically significant. Increased prostate-specific antigen serum concentrations without a diagnosis of prostate cancer in histopathologic examinations should not be an independent contraindication for performing organ transplantation. Nevertheless, for recipient safety, even when prostate cancer is only suspected in the frozen biopsy sample, the procured organ should not be used for transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2001-04-01

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

  18. Prostate Cancer Screening (PDQ®)—Patient Version

    Cancer.gov

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

  19. Cryotherapy for prostate cancer.

    PubMed

    Bermejo, Carlos E; Pisters, Louis L

    2003-06-01

    Cryotherapy, or the use of freezing, is a long-established method of tumor cell destruction. Although in the past cryotherapy was widely used as a local treatment for prostate cancer, this technique was abandoned not due to lack of efficacy but because the complication rate was unacceptably high. However, there has been a re-emergence in the popularity of cryotherapy for the treatment of localized prostate cancer due to improvements in instrumentation, tumor localization and treatment delivery. Using transrectal ultrasound imaging, prostate cryotherapy is currently delivered with multiple probes via a percutaneous transperineal approach. The extent of freezing can be precisely controlled and monitored with thermocouples and tissue destruction is monitored with real-time visualization of the prostate and surrounding structures. The role of cryotherapy in localized prostate cancer is reviewed.

  20. Prevention and Early Detection of Prostate Cancer

    PubMed Central

    Cuzick, Jack; Thorat, Mangesh A.; Andriole, Gerald; Brawley, Otis W.; Brown, Powel H.; Culig, Zoran; Eeles, Rosalind A.; Ford, Leslie G.; Hamdy, Freddie C.; Holmberg, Lars; Ilic, Dragan; Key, Timothy J.; La Vecchia, Carlo; Lilja, Hans; Marberger, Michael; Meyskens, Frank L.; Minasian, Lori M.; Parker, Chris; Parnes, Howard L.; Perner, Sven; Rittenhouse, Harry; Schalken, Jack; Schmid, Hans-Peter; Schmitz-Dräger, Bernd J.; Schröder, Fritz H.; Stenzl, Arnulf; Tombal, Bertrand; Wilt, Timothy J.; Wolk, Alicja

    2014-01-01

    Prostate cancer is one of the most common cancers in men and the global burden of this disease is rising. Lifestyle modifications like smoking cessation, exercise and weight control offer opportunities to decrease the risk of developing prostate cancer. Early detection of prostate cancer by PSA screening remains controversial; yet, changes in PSA threshold, frequency of screening, and addition of other biomarkers have potential to minimise overdiagnosis associated with PSA screening. Several new biomarkers appear promising in individuals with elevated PSA levels or those diagnosed with prostate cancer, these are likely to guide in separating individuals who can be spared of aggressive treatment from those who need it. Several pharmacological agents like 5α-reductase inhibitors, aspirin etc. have a potential to prevent development of prostate cancer. In this review, we discuss the current evidence and research questions regarding prevention, early detection of prostate cancer and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer. PMID:25281467

  1. A novel canine model for prostate cancer.

    PubMed

    Keller, Jill M; Schade, George R; Ives, Kimberly; Cheng, Xu; Rosol, Thomas J; Piert, Morand; Siddiqui, Javed; Roberts, William W; Keller, Evan T

    2013-06-01

    No existing animal model fully recapitulates all features of human prostate cancer. The dog is the only large mammal, besides humans, that commonly develops spontaneous prostate cancer. Canine prostate cancer features many similarities with its human counterpart. We sought to develop a canine model of prostate cancer that would more fully represent the features of human prostate cancer than existing models. The Ace-1 canine prostate cancer cell line was injected transabdominally under transrectal ultrasound (TRUS) guidance into the prostates of immunosuppressed, intact, adult male dogs. Tumor progression was monitored by TRUS imaging. Some dogs were subjected to positron emission tomography (PET) for tumor detection. Time of euthanasia was determined based on tumor size, impingement on urethra, and general well-being. Euthanasia was followed by necropsy and histopathology. Ace-1 tumor cells grew robustly in every dog injected. Tumors grew in subcapsular and parenchymal regions of the prostate. Tumor tissue could be identified using PET. Histological findings were similar to those observed in human prostate cancer. Metastases to lungs and lymph nodes were detected, predominantly in dogs with intraprostatic tumors. We have established a minimally invasive dog model of prostate cancer. This model may be valuable for studying prostate cancer progression and distant metastasis. Copyright © 2013 Wiley Periodicals, Inc.

  2. Differential Gene Expression in Benign Prostate Epithelium of Men with and without Prostate Cancer: Evidence for a Prostate Cancer Field Effect

    PubMed Central

    Risk, Michael C; Knudsen, Beatrice S; Coleman, Ilsa; Dumpit, Ruth F; Kristal, Alan R; LeMeur, Nolwenn; Gentleman, Robert C; True, Lawrence D; Nelson, Peter S; Lin, Daniel W

    2010-01-01

    Background Several malignancies are known to exhibit a “field-effect” whereby regions beyond tumor boundaries harbor histological or molecular changes that are associated with cancer. We sought to determine if histologically benign prostate epithelium collected from men with prostate cancer exhibits features indicative of pre-malignancy or field effect. Methods Prostate needle biopsies from 15 men with high grade(Gleason 8–10) prostate cancer and 15 age- and BMI-matched controls were identified from a biospecimen repository. Benign epithelia from each patient were isolated by laser capture microdissection. RNA was isolated, amplified, and used for microarray hybridization. Quantitative PCR(qPCR) was used to determine the expression of specific genes of interest. Alterations in protein expression were analyzed through immunohistochemistry. Results Overall patterns of gene expression in microdissected benign-associated benign epithelium (BABE) and cancer-associated benign epithelium (CABE) were similar. Two genes previously associated with prostate cancer, PSMA and SSTR1, were significantly upregulated in the CABE group(FDR <1%). Expression of other prostate cancer-associated genes, including ERG, HOXC4, HOXC5 and MME, were also increased in CABE by qRT-PCR, although other genes commonly altered in prostate cancer were not different between the BABE and CABE samples. The expression of MME and PSMA proteins on IHC coincided with their mRNA alterations. Conclusion Gene expression profiles between benign epithelia of patients with and without prostate cancer are very similar. However, these tissues exhibit differences in the expression levels of several genes previously associated with prostate cancer development or progression. These differences may comprise a field effect and represent early events in carcinogenesis. PMID:20935156

  3. Vitamin D in prostate cancer.

    PubMed

    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.

  4. Vitamin D in prostate cancer

    PubMed Central

    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

  5. Human Prostate Cancer Hallmarks Map

    PubMed Central

    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

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

    PubMed

    Chen, Rui; Xie, Liping; Xue, Wei; Ye, Zhangqun; Ma, Lulin; Gao, Xu; Ren, Shancheng; Wang, Fubo; Zhao, Lin; Xu, Chuanliang; Sun, Yinghao

    2016-09-01

    Substantial differences exist in the relationship of prostate cancer (PCa) detection rate and prostate-specific antigen (PSA) level between Western and Asian populations. Classic Western risk calculators, European Randomized Study for Screening of Prostate Cancer Risk Calculator, and Prostate Cancer Prevention Trial Risk Calculator, were shown to be not applicable in Asian populations. We aimed to develop and validate a risk calculator for predicting the probability of PCa and high-grade PCa (defined as Gleason Score sum 7 or higher) at initial prostate biopsy in Chinese men. Urology outpatients who underwent initial prostate biopsy according to the inclusion criteria were included. The multivariate logistic regression-based Chinese Prostate Cancer Consortium Risk Calculator (CPCC-RC) was constructed with cases from 2 hospitals in Shanghai. Discriminative ability, calibration and decision curve analysis were externally validated in 3 CPCC member hospitals. Of the 1,835 patients involved, PCa was identified in 338/924 (36.6%) and 294/911 (32.3%) men in the development and validation cohort, respectively. Multivariate logistic regression analyses showed that 5 predictors (age, logPSA, logPV, free PSA ratio, and digital rectal examination) were associated with PCa (Model 1) or high-grade PCa (Model 2), respectively. The area under the curve of Model 1 and Model 2 was 0.801 (95% CI: 0.771-0.831) and 0.826 (95% CI: 0.796-0.857), respectively. Both models illustrated good calibration and substantial improvement in decision curve analyses than any single predictors at all threshold probabilities. Higher predicting accuracy, better calibration, and greater clinical benefit were achieved by CPCC-RC, compared with European Randomized Study for Screening of Prostate Cancer Risk Calculator and Prostate Cancer Prevention Trial Risk Calculator in predicting PCa. CPCC-RC performed well in discrimination and calibration and decision curve analysis in external validation compared

  7. Should I Get Screened for Prostate Cancer?

    MedlinePlus

    ... about being screened for prostate cancer with a prostate specific antigen (PSA) test. Before making a decision, men should ... Task Force Prostate Cancer Screening Final Recommendation Understanding Prostate Changes: A Health ... Cancer Institute) What Is Screening? ...

  8. The Genomic Evolution of Prostate Cancer

    DTIC Science & Technology

    2017-06-01

    management and grant writing skills. 15. SUBJECT TERMS Cancer genetics , tumor evolution, tumor heterogeneity, prostate cancer, exome sequencing 16...aggressive disease, it is unclear if the genetic alterations more common in late disease are present early on, but at low frequency, or if they only...from localized to metastatic prostate cancer. 2. KEYWORDS: Cancer genetics , tumor evolution, tumor heterogeneity, prostate cancer, exome sequencing

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

    PubMed

    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.

  10. Highly Disordered Proteins in Prostate Cancer.

    PubMed

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

    2017-01-01

    Prostate cancer is one of the major threats to the man's health. There are several mechanisms of the prostate cancer development characterized by the involvement of various androgen-related and androgen-unrelated factors in prostate cancer pathogenesis and in the metastatic carcinogenesis of prostate. In all these processes, proteins play various important roles, and the KEGG database has information on 88 human proteins experimentally shown to be involved in prostate cancer. It is known that many proteins associated with different human maladies are intrinsically disordered (i.e., they do not have stable secondary and/or tertiary structure in their unbound states). The goal of this review is to consider several highly disordered proteins known to be associated with the prostate cancer pathogenesis in order to better understand the roles of disordered proteins in this disease. We also hope that consideration of the pathology-related proteins from the perspective of intrinsic disorder can potentially lead to future experimental studies of these proteins to find novel pathways associated with prostate cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Bortezomib reverses the proliferative and antiapoptotic effect of neuropeptides on prostate cancer cells.

    PubMed

    Tsapakidis, Konstantinos; Vlachostergios, Panagiotis J; Voutsadakis, Ioannis A; Befani, Christina D; Patrikidou, Anna; Hatzidaki, Eleana; Daliani, Danai D; Moutzouris, George; Liakos, Panagiotis; Papandreou, Christos N

    2012-06-01

    Neuropeptides are important signal initiators in advanced prostate cancer, partially acting through activation of nuclear factor kappa B. Central to nuclear factor kappa B regulation is the ubiquitin-proteasome system, pharmacological inhibition of which has been proposed as an anticancer strategy. We investigated the putative role of the proteasome inhibitor bortezomib in neuropeptides signaling effects on prostate cancer cells. Human prostate cancer cell lines, LNCaP and PC-3, were used to examine cell proliferation, levels of proapoptotic (caspase-3, Bad) and cell cycle regulatory proteins (p53, p27, p21), as well as total and phosphorylated Akt and p44/42 mitogen-activated protein kinase proteins. Furthermore, 20S proteasome activity, subcellular localization of nuclear factor kappa B and transcription of nuclear factor kappa B target genes, interleukin-8 and vascular endothelial growth factor, were assessed. Neuropeptides (endothelin-1, bombesin) increased cell proliferation, whereas bortezomib decreased proliferation and induced apoptosis, an effect maintained after cotreatment with neuropeptides. Bad, p53, p21 and p27 were downregulated by neuropeptides in PC-3, and these effects were reversed with the addition of bortezomib. Neuropeptides increased proteasomal activity and nuclear factor kappa B levels in PC-3, and these effects were prevented by bortezomib. Interleukin-8 and vascular endothelial growth factor transcripts were induced after neuropeptides treatment, but downregulated by bortezomib. These results coincided with the ability of bortezomib to reduce mitogen-activated protein kinase signaling in both cell lines. These findings are consistent with bortezomib-mediated abrogation of neuropeptides-induced proliferative and antiapoptotic signaling. Thus, the effect of the drug on the neuropeptides axis needs to be further investigated, as neuropeptide action in prostate cancer might entail involvement of the proteasome. © 2012 The Japanese Urological

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

    PubMed

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

    2016-06-01

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

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

    PubMed Central

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

    2016-01-01

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

  14. Epigenetics in Prostate Cancer

    PubMed Central

    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. PMID:22191037

  15. Epigenetics in prostate cancer.

    PubMed

    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.

  16. Prostate cancer: a patient's perspective.

    PubMed

    Howe, R J

    1994-11-01

    During the last few years a tremendous amount of media attention has been focused on prostate cancer. This increased visibility has been the direct result of the prostate specific antigen test, which has led to a doubling of the number of new cases detected in just 4 years. With this visibility has come controversy about which treatment is the most effective or whether this disease should be treated aggressively at all. The formation and rapid expansion of the prostate cancer support group movement are reviewed, and the positive and negative impacts of media coverage on present and future patients are assessed. My personal case is reviewed briefly to make a specific point about the hazards of watchful waiting. Other issues, such as mass screening, Prostate Cancer Awareness Week and expenditures for prostate cancer research, are examined in some detail.

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

    PubMed

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

    2015-07-01

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

  18. Molecular Characterization of Indolent Prostate Cancer

    DTIC Science & Technology

    2016-12-01

    prostate - specific antigen (PSA) test, and treated aggressively following diagnosis, leading to the contemporary problem of prostate cancer over-diagnosis... specific purpose of comparing low- risk and high-risk prostate cancer. Figure 3 shows the mapping rates for exon, intron, and inter-genic sequences. The...FFPE specimens, for the specific comparison of low-risk and high-risk prostate cancer. 5. Identified sufficient number of biopsy cases and sections

  19. Tea, coffee and prostate cancer.

    PubMed

    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.

  20. Development of New Treatments for Prostate Cancer

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

    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 ofmore » 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

  1. Serum ferritin in combination with prostate-specific antigen improves predictive accuracy for prostate cancer.

    PubMed

    Wang, Xijuan; An, Peng; Zeng, Jiling; Liu, Xiaoyan; Wang, Bo; Fang, Xuexian; Wang, Fudi; Ren, Guoping; Min, Junxia

    2017-03-14

    Ferritin is highly expressed in many cancer types. Although a few studies have reported an association between high serum ferritin levels and an increased risk of prostate cancer, the results are inconsistent. Therefore, we performed a large case-control study consisting of 2002 prostate cancer patients and 951 control patients with benign prostatic hyperplasia (BPH). We found that high ferritin levels were positively associated with increased serum prostate-specific antigen (PSA) levels and prostate cancer risk; each 100 ng/ml increase in serum ferritin increased the odds ratio (OR) by 1.20 (95% CI: 1.13-1.36). In the prostate cancer group, increased serum ferritin levels were significantly correlated with higher Gleason scores (p < 0.001). Notably, serum PSA values had even higher predictive accuracy among prostate cancer patients with serum ferritin levels > 400 ng/ml (Gleason score + total PSA correlation: r = 0.38; Gleason score + free PSA correlation: r = 0.49). Moreover, using immunohistochemistry, we found that prostate tissue ferritin levels were significantly higher (p < 0.001) in prostate cancer patients (n = 129) compared to BPH controls (n = 31). Prostate tissue ferritin levels were also highly correlated with serum ferritin when patients were classified by cancer severity (r = 0.81). Importantly, we found no correlation between serum ferritin levels and the inflammation marker C-reactive protein (CRP) in prostate cancer patients. In conclusion, serum ferritin is significantly associated with prostate cancer and may serve as a non-invasive biomarker to complement the PSA test in the diagnosis and prognostic evaluation of prostate cancer.

  2. New Prostate Cancer Treatment Target

    Cancer.gov

    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.

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

    DTIC Science & Technology

    2015-10-01

    1 AWARD NUMBER: W81XWH-14-1-0531 TITLE: Roswell Park Cancer Institute / Howard University Prostate Cancer Scholars Program PRINCIPAL...TITLE AND SUBTITLE Roswell Park Cancer Institute/Howard University Prostate Cancer 5a. CONTRACT NUMBER W81XWH-14-1-0531 Cancer Scholars Program 5b...ABSTRACT The Roswell Park/Howard University Prostate Cancer Scholars Program is designed to encourage students from under-represented minority groups

  4. Risks of Prostate Cancer Screening

    MedlinePlus

    ... decrease the risk of dying from cancer. Scientists study screening tests to find those with the fewest risks and ... or routine screening test for prostate cancer. Screening tests for prostate cancer are under study, and there are screening clinical trials taking place ...

  5. Metabolomic signatures of aggressive prostate cancer.

    PubMed

    McDunn, Jonathan E; Li, Zhen; Adam, Klaus-Peter; Neri, Bruce P; Wolfert, Robert L; Milburn, Michael V; Lotan, Yair; Wheeler, Thomas M

    2013-10-01

    Current diagnostic techniques have increased the detection of prostate cancer; however, these tools inadequately stratify patients to minimize mortality. Recent studies have identified a biochemical signature of prostate cancer metastasis, including increased sarcosine abundance. This study examined the association of tissue metabolites with other clinically significant findings. A state of the art metabolomics platform analyzed prostatectomy tissues (331 prostate tumor, 178 cancer-free prostate tissues) from two independent sites. Biochemicals were analyzed by gas chromatography-mass spectrometry and ultrahigh performance liquid chromatography-tandem mass spectrometry. Statistical analyses identified metabolites associated with cancer aggressiveness: Gleason score, extracapsular extension, and seminal vesicle and lymph node involvement. Prostate tumors had significantly altered metabolite profiles compared to cancer-free prostate tissues, including biochemicals associated with cell growth, energetics, stress, and loss of prostate-specific biochemistry. Many metabolites were further associated with clinical findings of aggressive disease. Aggressiveness-associated metabolites stratified prostate tumor tissues with high abundances of compounds associated with normal prostate function (e.g., citrate and polyamines) from more clinically advanced prostate tumors. These aggressive prostate tumors were further subdivided by abundance profiles of metabolites including NAD+ and kynurenine. When added to multiparametric nomograms, metabolites improved prediction of organ confinement (AUROC from 0.53 to 0.62) and 5-year recurrence (AUROC from 0.53 to 0.64). These findings support and extend earlier metabolomic studies in prostate cancer and studies where metabolic enzymes have been associated with carcinogenesis and/or outcome. Furthermore, these data suggest that panels of analytes may be valuable to translate metabolomic findings to clinically useful diagnostic tests

  6. Prostate cancer and social media.

    PubMed

    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.

  7. Evaluating long-term patient-centered outcomes following prostate cancer treatment: findings from the Michigan Prostate Cancer Survivor study.

    PubMed

    Darwish-Yassine, May; Berenji, Manijeh; Wing, Diane; Copeland, Glenn; Demers, Raymond Y; Garlinghouse, Carol; Fagerlin, Angela; Newth, Gail E; Northouse, Laurel; Holmes-Rovner, Margaret; Rovner, David; Sims, Jerry; Wei, John T

    2014-03-01

    Advances in screening and treatment of prostate cancer have dramatically increased the number of survivors in the US population. Yet the effect of screening is controversial, and in some instances may not be beneficial. Previous studies have typically only reported outcomes of treatment and symptoms within a short time frame following treatment. The persistence of such symptoms over time necessitates an improvement of survivor care so that the medical and support needs of these patients are met. This study aims to perform a patient-centered survey of prostate cancer survivors in the Michigan Cancer Registry to identify treatment side effect rates, evaluate survivors' access to preventive care services post-prostate cancer treatment, and assess the informational needs of these survivors regarding their prostate cancer. Linking case files of the Michigan Cancer Registry with records from the National Death Index, we identified prostate cancer patients diagnosed between 1985 and 2004 and alive on 31 December 2005. Participants were selected using a stratified cross-sectional sampling strategy to ensure adequate inclusion of survivors based upon race and ethnicity, urban versus rural location, and number of years since diagnosis of prostate cancer. A total of 2,499 surveys were completed and returned. (1) Physical symptoms--assessing bowel, sexual, urinary, and vitality symptoms by treatment modality. (2) Access to care--identifying whether diagnostic tests for prostate cancer (prostate-specific antigen (PSA) and digital rectal examination) were performed. Determining whether the survivors had knowledge of the "watchful waiting" paradigm for prostate cancer surveillance. (3) Informational needs--assessing whether the informational needs of patients were addressed by providers. Evaluating the significant predictors associated with seeking information about prostate cancer from any other source. Identifying what factors influenced a person to actively seek out

  8. Vitamins, Metabolomics and Prostate Cancer

    PubMed Central

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

    2016-01-01

    Purpose 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 by which vitamins influence prostate cancer risk. Methods Prostate cancer risk data related to vitamins E, A, and D and metabolomics 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. Results 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 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 metabolomics profiling of fasting serum collected 1-20 years prior to clinical diagnoses found lipid and energy/TCA cycle metabolites, including inositol-1-phosphate, lysolipids, alpha-ketoglutarate, and citrate, significantly associated with risk of aggressive disease. Conclusions 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. PMID:27339624

  9. Vitamins, metabolomics, and prostate cancer.

    PubMed

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

    2017-06-01

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

  10. Key papers in prostate cancer.

    PubMed

    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.

  11. Prostate-specific antigen screening and mortality from prostate cancer.

    PubMed

    Marcella, Stephen W; Rhoads, George G; Carson, Jeffrey L; Merlino, Frances; Wilcox, Homer

    2008-03-01

    There is no available evidence from randomized trials that early detection of prostate cancer improves health outcomes, but the prostate-specific antigen (PSA) test is commonly used to screen men for prostate cancer. The objective of the study is to see if screening with PSA decreases mortality from prostate cancer. This is a case-control study using one-to-one matching on race, age, and time of availability of exposure to PSA screening. Decedents, 380, from New Jersey Vital Statistics 1997 to 2000 inclusive, 55-79 years of age at diagnosis were matched to living controls without metastatic prostate cancer. Medical records were obtained from all providers, and we abstracted information about PSA tests from 1989 to the time of diagnosis in each index case. Measurements consist of a comparison of screening (yes, no) between cases and controls. Measure of association was the odds ratio. Eligible cases were diagnosed each year from 1989 to 1999 with the median year being 1993. PSA screening was evident in 23.2-29.2% of cases and 21.8-26.1% of controls depending on the screening criteria. The unadjusted, matched odds ratio for dying of prostate cancer if ever screened was 1.09 (95% CI 0.76 to 1.60) for the most restrictive criteria and 1.19 (95% CI, 0.85 to 1.66) for the least restrictive. Adjustment for comorbidity and education level made no significant differences in these values. There were no significant interactions by age or race. PSA screening using an ever/never tabulation for tests from 1989 until 2000 did not protect New Jersey men from prostate cancer mortality.

  12. Prostate Cancer: Serum and Tissue Markers

    PubMed Central

    Miller, Gary J; Brawer, Michael K; Sakr, Wael A; Thrasher, J Brantley; Townsend, Ronald

    2001-01-01

    The detection of prostate cancer, its clinical staging, and the prediction of its prognosis remain topics of paramount importance in clinical management. The digital rectal exam, although once the “gold standard,” has been largely supplanted by a variety of techniques including serum and tissue-based assays. This article reviews recent progress in the development of prostate-specific antigen assays with greater specificity; molecular markers for prostate cancer (DNA ploidy, nuclear morphometry, markers of proliferation, and cell adhesion molecules); the link between vitamin D deficiency and the clinical emergence of prostate cancer; the possible correlation of serum insulin-like growth factor levels with the risk for developing prostate cancer; and the latest advances in radiologic staging. PMID:16985995

  13. Prostate Cancer and Bone: The Elective Affinities

    PubMed Central

    2014-01-01

    The onset of metastases dramatically changes the prognosis of prostate cancer patients, determining increased morbidity and a drastic fall in survival expectancy. Bone is a common site of metastases in few types of cancer, and it represents the most frequent metastatic site in prostate cancer. Of note, the prevalence of tumor relapse to the bone appears to be increasing over the years, likely due to a longer overall survival of prostate cancer patients. Bone tropism represents an intriguing challenge for researchers also because the preference of prostate cancer cells for the bone is the result of a sequential series of targetable molecular events. Many factors have been associated with the peculiar ability of prostate cancer cells to migrate in bone marrow and to determine mixed osteoblastic/osteolytic lesions. As anticipated by the success of current targeted therapy aimed to block bone resorption, a better understanding of molecular affinity between prostate cancer and bone microenvironment will permit us to cure bone metastasis and to improve prognosis of prostate cancer patients. PMID:24971315

  14. Testosterone Therapy in Men With Prostate Cancer

    PubMed Central

    Kaplan, Alan L.; Hu, Jim C.; Morgentaler, Abraham; Mulhall, John P.; Schulman, Claude C.; Montorsi, Francesco

    2016-01-01

    Context The use of testosterone therapy in men with prostate cancer was previously contraindicated, although recent data challenge this axiom. Over the past 2 decades, there has been a dramatic paradigm shift in beliefs, attitude, and treatment of testosterone deficiency in men with prostate cancer. Objective To summarize and analyze current literature regarding the effect of testosterone replacement in men with prostate cancer. Evidence acquisition We conducted a Medline search to identify all publications related to testosterone therapy in both treated and untreated prostate cancer. Evidence synthesis The historical notion that increasing testosterone was responsible for prostate cancer growth was based on elegant yet limited studies from the 1940s and anecdotal case reports. Current evidence reveals that high endogenous androgen levels do not increase the risk of a prostate cancer diagnosis. Similarly, testosterone therapy in men with testosterone deficiency does not appear to increase prostate cancer risk or the likelihood of a more aggressive disease at prostate cancer diagnosis. Androgen receptor saturation (the saturation model) appears to account for this phenomenon. Men who received testosterone therapy after treatment for localized prostate cancer do not appear to suffer higher rates of recurrence or worse outcomes; although studies to date are limited. Early reports of men on active surveillance/watchful waiting treated with testosterone have not identified adverse progression events. Conclusions An improved understanding of the negative effects of testosterone deficiency on health and health-related quality of life—and the ability of testosterone therapy to mitigate these effects—has triggered a re-evaluation of the role testosterone plays in prostate cancer. An important paradigm shift has occurred within the field, in which testosterone therapy may now be regarded as a viable option for selected men with prostate cancer suffering from testosterone

  15. Punctuated Evolution of Prostate Cancer Genomes

    PubMed Central

    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.

    2013-01-01

    SUMMARY 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. PMID:23622249

  16. Punctuated evolution of prostate cancer genomes.

    PubMed

    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.

  17. Counseling the Client with Prostate Cancer.

    ERIC Educational Resources Information Center

    Curtis, Russell C.; Juhnke, Gerald A.

    2003-01-01

    Prostate cancer is prevalent in the United States and has a far-reaching effect on men and their relationships. Being diagnosed with and treated for prostate cancer often causes men to experience side effects that induce physical, emotional, and social change. Counselors need to be aware of prostate cancer's impact on men and their families.…

  18. What do prostate cancer patients die of?

    PubMed

    Riihimäki, Matias; Thomsen, Hauke; Brandt, Andreas; Sundquist, Jan; Hemminki, Kari

    2011-01-01

    A recent rise in the incidence of prostate cancer and a more favorable outcome have increased the proportions of other causes of death in affected men. Extending the survival of prostate cancer patients thus requires knowledge of all causes of death. Data on the population, cancers, and causes of death were gathered from the nationwide Swedish Family-Cancer Database. A Cox regression model, comparing prostate cancer patients with all other men, was applied. Hazard ratios (HR) were calculated both for the underlying cause and for dying with a specific cause listed among multiple causes of death. Among 686,500 observed deaths, 62,500 were prostate cancer patients. For underlying causes other than prostate cancer, the highest cause-specific HRs were found for external causes (HR, 1.24; 95% confidence interval [CI], 1.16-1.31), diseases of the pulmonary circulation (HR, 1.22; 95% CI, 1.09-1.37), and heart failure (HR, 1.18; 95% CI, 1.11-1.24). For specific multiple causes, the highest HRs were found for anemia (HR, 2.28; 95% CI, 2.14-2.42), diseases of the pulmonary circulation (HR, 1.61; 95% CI, 1.55-1.68), and urinary system disease (HR, 1.90; 95% CI, 1.84-1.96). Prostate cancer patients have a higher risk for dying from various causes other than prostate cancer, including external causes and heart failure. Mechanisms have been proposed linking these elevated risks to both cancer and treatment. More attention should be paid to comorbidities in men with prostate cancer. The present study fulfills a gap in the knowledge of death causes in prostate cancer patients.

  19. Nine-year prostate cancer survival differences between aggressive versus conservative therapy in men with advanced and metastatic prostate cancer.

    PubMed

    Dall'Era, Marc A; Lo, Mary J; Chen, Jaclyn; Cress, Rosemary; Hamilton, Ann S

    2018-05-01

    To the authors' knowledge, the survival benefit of local therapy in the setting of advanced prostate cancer remains unknown. The authors investigated whether prostate-directed treatment with either surgery or radiotherapy versus conservative treatment in the setting of locally advanced or metastatic disease was associated with improved survival within a cohort of men from the Centers for Disease Control and Prevention's (CDC) Breast and Prostate Cancer Data Quality and Patterns of Care Study (CDC POC-BP). Men diagnosed with locally advanced (cT3-T4 or N+ and M0) or metastatic prostate cancer were identified. The authors compared survival by treatment type, categorized as conservative (androgen deprivation therapy only) versus aggressive (radical prostatectomy or any type of radiotherapy). Nine-year overall survival and prostate cancer-specific survival were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to determine factors independently associated with 9-year prostate cancer-specific survival. For men with advanced, nonmetastatic prostate cancer, conservative treatment alone was associated with a 4 times higher likelihood of prostate cancer mortality compared with men treated with surgery (hazard ratio, 4.18; 95% confidence interval, 1.44-12.14). In contrast, no difference was found between conservative versus aggressive treatment after adjusting for covariates for men with metastatic disease. The 9-year prostate cancer-specific survival rate was 27% for those receiving aggressive treatment versus 24% for men undergoing conservative treatment. The authors did not observe a survival advantage with local therapy in addition to standard androgen deprivation therapy for men with metastatic prostate cancer. However, the results of the current study did affirm advantages in the setting of locally advanced disease. Aggressive local therapy in the setting of metastatic disease needs to be studied carefully before clinical adoption

  20. Prostate cancer chemoprevention agent development: the National Cancer Institute, Division of Cancer Prevention portfolio.

    PubMed

    Parnes, Howard L; House, Margaret G; Kagan, Jacob; Kausal, David J; Lieberman, Ronald

    2004-02-01

    We describe the current National Cancer Institute chemoprevention agent development program and provide a summary of the intermediate end points used. The National Cancer Institute is currently sponsoring a wide range of studies of promising chemoprevention agents in a variety of informative cohorts, eg high grade prostatic intraepithelial neoplasia, positive family history of cancer, increased prostate specific antigen with negative biopsies, prostate cancer followed expectantly, prostate cancer awaiting definitive therapy and the general population. The rationale for each agent under investigation is derived from epidemiological observations, prostate cancer treatment trials, secondary analyses of large cancer prevention studies, an understanding of cancer biology and prostate carcinogenesis, and/or experimental animal models. Carcinogenesis is a multistep process occurring over decades which is characterized by disruption of the normal regulatory pathways controlling cellular proliferation, programmed cell death and differentiation. Administration of agents to reverse, inhibit or slow this process of malignant transformation is known as chemoprevention. Chemoprevention represents a promising approach to reducing the morbidity and mortality of prostate cancer. A variety of agents are currently being studied in phase 2 clinical trials, some of which may warrant subsequent evaluation in phase 3 trials with definitive cancer end points. Two large phase 3 trials, the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial, which are ongoing, are also sponsored by the National Cancer Institute.

  1. Quality of Prostate Cancer Treatment Information on Cancer Center Websites.

    PubMed

    Dulaney, Caleb; Barrett, Olivia Claire; Rais-Bahrami, Soroush; Wakefield, Daniel; Fiveash, John; Dobelbower, Michael

    2016-04-20

    Cancer center websites are trusted sources of internet information about treatment options for prostate cancer. The quality of information on these websites is unknown. The objective of this study was to evaluate the quality of information on cancer center websites addressing prostate cancer treatment options, outcomes, and toxicity. We evaluated the websites of all National Cancer Institute-designated cancer centers to determine if sufficient information was provided to address eleven decision-specific knowledge questions from the validated Early Prostate Cancer Treatment Decision Quality Instrument. We recorded the number of questions addressed, the number of clicks to reach the prostate cancer-specific webpage, evaluation time, and Spanish and mobile accessibility. Correlation between evaluation time and questions addressed were calculated using the Pearson coefficient. Sixty-three websites were reviewed. Eighty percent had a prostate cancer-specific webpage reached in a median of three clicks. The average evaluation time was 6.5 minutes. Information was available in Spanish on 24% of sites and 59% were mobile friendly. Websites provided sufficient information to address, on average, 19% of questions. No website addressed all questions. Evaluation time correlated with the number of questions addressed (R(2) = 0.42, p < 0.001). Cancer center websites provide insufficient information for men with localized prostate cancer due to a lack of information about and direct comparison of specific treatment outcomes and toxicities. Information is also less accessible in Spanish and on mobile devices. These data can be used to improve the quality and accessibility of prostate cancer treatment information on cancer center websites.

  2. Survival in prostate cancer prevention trial detailed

    Cancer.gov

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

  3. Prostate-Specific Antigen Screening and Mortality from Prostate Cancer

    PubMed Central

    Rhoads, George G.; Carson, Jeffrey L.; Merlino, Frances; Wilcox, Homer

    2008-01-01

    Background There is no available evidence from randomized trials that early detection of prostate cancer improves health outcomes, but the prostate-specific antigen (PSA) test is commonly used to screen men for prostate cancer. Objective The objective of the study is to see if screening with PSA decreases mortality from prostate cancer. Design, setting, and participants This is a case-control study using one-to-one matching on race, age, and time of availability of exposure to PSA screening. Decedents, 380, from New Jersey Vital Statistics 1997 to 2000 inclusive, 55–79 years of age at diagnosis were matched to living controls without metastatic prostate cancer. Medical records were obtained from all providers, and we abstracted information about PSA tests from 1989 to the time of diagnosis in each index case. Measurements Measurements consist of a comparison of screening (yes, no) between cases and controls. Measure of association was the odds ratio. Results Eligible cases were diagnosed each year from 1989 to 1999 with the median year being 1993. PSA screening was evident in 23.2–29.2% of cases and 21.8–26.1% of controls depending on the screening criteria. The unadjusted, matched odds ratio for dying of prostate cancer if ever screened was 1.09 (95% CI 0.76 to 1.60) for the most restrictive criteria and 1.19 (95% CI, 0.85 to 1.66) for the least restrictive. Adjustment for comorbidity and education level made no significant differences in these values. There were no significant interactions by age or race. Conclusions PSA screening using an ever/never tabulation for tests from 1989 until 2000 did not protect New Jersey men from prostate cancer mortality. PMID:18172740

  4. General Information about Prostate Cancer

    MedlinePlus

    ... Research Prostate Cancer Treatment (PDQ®)–Patient Version General Information About Prostate Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  5. Genetic variation: effect on prostate cancer

    PubMed Central

    Sissung, Tristan M.; Price, Douglas K.; Del Re, Marzia; Ley, Ariel M.; Giovannetti, Elisa; Danesi, Romano

    2014-01-01

    Summary The crucial role of androgens in the development of prostate cancer is well established. The aim of this review is to examine the role of constitutional (germline) and tumor-specific (somatic) polymorphisms within important regulatory genes of prostate cancer. These include genes encoding enzymes of the androgen biosynthetic pathway, the androgen receptor gene, genes that encode proteins of the signal transduction pathways that may have a role in disease progression and survival, and genes involved in prostate cancer angiogenesis. Characterization of deregulated pathways critical to cancer cell growth have lead to the development of new treatments, including the CYP17 inhibitor abiraterone and clinical trials using novel drugs that are ongoing or recently completed [1]. The pharmacogenetics of the drugs used to treat prostate cancer will also be addressed. This review will define how germline polymorphisms are known affect a multitude of pathways, and therefore phenotypes, in prostate cancer etiology, progression, and treatment. PMID:25199985

  6. Cabazitaxel for the treatment of prostate cancer.

    PubMed

    Michielsen, Dirk P J; Braeckman, Johan G; Denis, Louis

    2011-04-01

    Prostate cancer is a frequently diagnosed male cancer. In men presenting locally advanced or metastatic disease, the mainstay of treatment is hormonal suppression. Despite the castrate levels of testosterone, with time, prostate cancer gradually evolves into a castration-refractory state. Chemotherapeutic agents are able to influence the natural history of metastatic castration-resistant prostate cancer. Docetaxel is a clinically relevant, FDA-approved taxane. Today, it is the first-line chemotherapeutic agent in castration-refractory prostate cancer (CRPC). There is no standard second-line chemotherapeutic regimen. This review provides information on the efficacy of cabazitaxel as a second-line treatment for CRPC. The medline database was searched for clinical trials on chemotherapeutical treatment options of castration-resistant prostate cancer. All available data on the efficacy of cabazitaxel are summarized. New treatment strategies for castration-resistant prostate cancer should primarily focus on quality of life. In this view, vaccination therapy seems promising because of the acceptable level of toxicity. However, more research is needed to prove their efficacy in the treatment of castration-resistant prostate cancer. Cabazitaxel seems to be a promising second-line therapy in CRPC.

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

    PubMed

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

    2016-08-01

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

  8. Estrogen action and prostate cancer

    PubMed Central

    Nelles, Jason L; Hu, Wen-Yang; Prins, Gail S

    2011-01-01

    Early work on the hormonal basis of prostate cancer focused on the role of androgens, but more recently estrogens have been implicated as potential agents in the development and progression of prostate cancer. In this article, we review the epidemiological, laboratory and clinical evidence that estrogen may play a causative role in human prostate cancer, as well as rodent and grafted in vivo models. We then review recent literature highlighting potential mechanisms by which estrogen may contribute to prostate cancer, including estrogenic imprinting and epigenetic modifications, direct genotoxicity, hyperprolactinemia, inflammation and immunologic changes, and receptor-mediated actions. We discuss the work performed so far separating the actions of the different known estrogen receptors (ERs), ERα and ERβ, as well as G-protein-coupled receptor 30 and their specific roles in prostate disease. Finally, we predict that future work in this field will involve more investigations into epigenetic changes, experiments using new models of hormonal dysregulation in developing human prostate tissue, and continued delineation of the roles of the different ER subtypes, as well as their downstream signaling pathways that may serve as therapeutic targets. PMID:21765856

  9. Prostate Cancer FAQs

    MedlinePlus

    ... over and African-American or have a family history of prostate cancer, you need more than a good ... cancer is the most common non-skin cancer in America, affecting 1 in 9 men. In 2018, nearly ...

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

    PubMed Central

    2014-01-01

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

  11. Prostate Cancer Screening (PDQ®)—Health Professional Version

    Cancer.gov

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

  12. Current state of prostate cancer treatment in Jamaica.

    PubMed

    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

  13. The Infectious Pathogenesis of Prostate Cancer

    DTIC Science & Technology

    2010-03-01

    of cancers, including prostate. Infections are important agents in the genesis of inflammation. For prostate cancer, several lines of evidence point...to a role of infections as important agents , although no specific infection has consistently been identified. In this project, we are examining two...specific infectious agents with respect to prostate cancer: T vaginalis, the most common non-viral sexually transmitted infection, and the recently

  14. Radiomics and radiogenomics of prostate cancer.

    PubMed

    Smith, Clayton P; Czarniecki, Marcin; Mehralivand, Sherif; Stoyanova, Radka; Choyke, Peter L; Harmon, Stephanie; Turkbey, Baris

    2018-06-20

    Radiomics and radiogenomics are attractive research topics in prostate cancer. Radiomics mainly focuses on extraction of quantitative information from medical imaging, whereas radiogenomics aims to correlate these imaging features to genomic data. The purpose of this review is to provide a brief overview summarizing recent progress in the application of radiomics-based approaches in prostate cancer and to discuss the potential role of radiogenomics in prostate cancer.

  15. Association of Reported Prostate Cancer Risk Alleles With PSA Levels Among Men Without a Diagnosis of Prostate Cancer

    PubMed Central

    Wiklund, Fredrik; Zheng, S. Lilly; Sun, Jielin; Adami, Hans-Olov; Lilja, Hans; Hsu, Fang-Chi; Stattin, Pär; Adolfsson, Jan; Cramer, Scott D.; Duggan, David; Carpten, John D.; Chang, Bao-Li; Isaacs, William B.; Grönberg, Henrik; Xu, Jianfeng

    2012-01-01

    BACKGROUND Prostate specific antigen (PSA) is widely used for prostate cancer screening but its levels are influenced by many non cancer-related factors. The goal of the study is to estimate the effect of genetic variants on PSA levels. METHODS We evaluated the association of SNPs that were reported to be associated with prostate cancer risk in recent genome-wide association studies with plasma PSA levels in a Swedish study population, including 1,722 control subjects without a diagnosis of prostate cancer. RESULTS Of the 16 SNPs analyzed in control subjects, significant associations with PSA levels (P≤0.05) were found for six SNPs. These six SNPs had a cumulative effect on PSA levels; the mean PSA levels in men were almost twofold increased across increasing quintile of number of PSA associated alleles, P-trend=3.4×10−14. In this Swedish study population risk allele frequencies were similar among T1c case patients (cancer detected by elevated PSA levels alone) as compared to T2 and above prostate cancer case patients. CONCLUSIONS Results from this study may have two important clinical implications. The cumulative effect of six SNPs on PSA levels suggests genetic-specific PSA cutoff values may be used to improve the discriminatory performance of this test for prostate cancer; and the dual associations of these SNPs with PSA levels and prostate cancer risk raise a concern that some of reported prostate cancer risk-associated SNPs may be confounded by the prevalent use of PSA screening. PMID:19116992

  16. Can the Mediterranean diet prevent prostate cancer?

    PubMed

    Itsiopoulos, Catherine; Hodge, Allison; Kaimakamis, Mary

    2009-02-01

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

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

    PubMed Central

    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.

    2015-01-01

    Background 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. Methods 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. Results 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. Conclusions These findings suggest that telomere shortening in normal stromal cells is associated with prostate cancer risk. It is essential to

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

    PubMed

    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

  19. Prostate and Urologic Cancer | Division of Cancer Prevention

    Cancer.gov

    [[{"fid":"183","view_mode":"default","fields":{"format":"default","field_file_image_alt_text[und][0][value]":"Prostate and Urologic Cancer Research Group Homepage Logo","field_file_image_title_text[und][0][value]":"Prostate and Urologic Cancer Research Group Homepage

  20. Prostate Cancer Patients' Refusal of Cancer-Directed Surgery: A Statewide Analysis

    PubMed Central

    Islam, K. M.

    2015-01-01

    Introduction. Prostate cancer is the most common cancer among men in USA. The surgical outcomes of prostate cancer remain inconsistent. Barriers such as socioeconomic factors may play a role in patients' decision of refusing recommended cancer-directed surgery. Methods. The Nebraska Cancer Registry data was used to calculate the proportion of prostate cancer patients recommended the cancer-directed surgery and the surgery refusal rate. Multivariate logistic regression was applied to analyze the socioeconomic indicators that were related to the refusal of surgery. Results. From 1995 to 2012, 14,876 prostate cancer patients were recommended to undergo the cancer-directed surgery in Nebraska, and 576 of them refused the surgery. The overall refusal rate of surgery was 3.9% over the 18 years. Patients with early-stage prostate cancer were more likely to refuse the surgery. Patients who were Black, single, or covered by Medicaid/Medicare had increased odds of refusing the surgery. Conclusion. Socioeconomic factors were related to the refusal of recommended surgical treatment for prostate cancer. Such barriers should be addressed to improve the utilization of surgical treatment and patients' well-being. PMID:25973276

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

    PubMed Central

    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

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

    PubMed

    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.

  3. Prostate Cancer Screening Results from PLCO

    Cancer.gov

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

  4. Identification of the epigenetic reader CBX2 as a potential drug target in advanced prostate cancer.

    PubMed

    Clermont, Pier-Luc; Crea, Francesco; Chiang, Yan Ting; Lin, Dong; Zhang, Amy; Wang, James Z L; Parolia, Abhijit; Wu, Rebecca; Xue, Hui; Wang, Yuwei; Ding, Jiarui; Thu, Kelsie L; Lam, Wan L; Shah, Sohrab P; Collins, Colin C; Wang, Yuzhuo; Helgason, Cheryl D

    2016-01-01

    While localized prostate cancer (PCa) can be effectively cured, metastatic disease inevitably progresses to a lethal state called castration-resistant prostate cancer (CRPC). Emerging evidence suggests that aberrant epigenetic repression by the polycomb group (PcG) complexes fuels PCa progression, providing novel therapeutic opportunities. In the search for potential epigenetic drivers of CRPC, we analyzed the molecular profile of PcG members in patient-derived xenografts and clinical samples. Overall, our results identify the PcG protein and methyl-lysine reader CBX2 as a potential therapeutic target in advanced PCa. We report that CBX2 was recurrently up-regulated in metastatic CRPC and that elevated CBX2 expression was correlated with poor clinical outcome in PCa cohorts. Furthermore, CBX2 depletion abrogated cell viability and induced caspase 3-mediated apoptosis in metastatic PCa cell lines. Mechanistically explaining this phenotype, microarray analysis in CBX2-depleted cells revealed that CBX2 controls the expression of many key regulators of cell proliferation and metastasis. Taken together, this study provides the first evidence that CBX2 inhibition induces cancer cell death, positioning CBX2 as an attractive drug target in lethal CRPC.

  5. IAP Antagonists Enhance Apoptotic Response to Enzalutamide in Castration-Resistant Prostate Cancer Cells via Autocrine TNF-α Signaling.

    PubMed

    Pilling, Amanda B; Hwang, Ok; Boudreault, Alain; Laurent, Alain; Hwang, Clara

    2017-06-01

    RNA expression and autocrine protein secretion. Blocking TNF-α signaling abrogates the apoptotic response demonstrating that TNF-α plays a critical role in executing cell death in response to this drug combination. These findings suggest that IAP antagonists can increase sensitivity and amplify the caspase-mediated apoptotic response to enzalutamide through TNF-α signaling mechanisms. Combination with an IAP antagonist increases enzalutamide sensitivity, lowers the apoptotic threshold and may combat drug resistance in patients with prostate cancer. Prostate 77:866-877, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Wnt Signaling in Prostate Cancer Bone Metastases

    DTIC Science & Technology

    2015-09-01

    Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Ace-1-Dkk-1, a canine prostate cancer overexpressing Dkk-1 is used in this study to investigate how...Dkk-1 expression in prostate cancer could change the metastatic phenotype and tumor growth in vivo. Ace-1-Dkk-1, a canine prostate cancer

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

    PubMed

    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.

  8. Exploiting Epigenetic Alterations in Prostate Cancer.

    PubMed

    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.

  9. Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer

    DTIC Science & Technology

    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

  10. Regulating Cancer Associated Fibroblast Biology in Prostate Cancer

    DTIC Science & Technology

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0512 TITLE: Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer PRINCIPAL INVESTIGATOR: Andrew...CONTRACT NUMBER Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0512 5c. PROGRAM ELEMENT NUMBER 6... biology to modulate epithelial growth and that inhibitors of this protein kinase have the potential to block this process and thus inhibit tumor growth

  11. Hypofractionation for Prostate Cancer

    PubMed Central

    Ritter, Mark; Forman, Jeffrey; Kupelian, Patrick; Lawton, Colleen; Petereit, Daniel

    2011-01-01

    Hypofractionation for prostate cancer was originally carried out in the pursuit of efficiency and convenience, but has now attracted greatly renewed interest based upon a hypothesis that prostate cancers have a higher sensitivity to fraction size, reflected in a low α/β ratio, then do late responding organs at risk such as the rectum or bladder. Tumor control and acceptable toxicity outcomes from several hypofractionation or brachytherapy analyses do in fact support an α/β ratio for prostate cancer that is low, perhaps even lower that that for the normal organs that ordinarily constrain the delivery of radiation therapy. However, many of these studies lack sufficient patient numbers and follow-up, are clouded by dose inhomogeneity issues in the case of brachytherapy, or delivered effective doses that were too low by contemporary standards. Thus, the clinical efficacy of the approach has yet to be fully validated. However, a number of newer prospective trials, some randomized, are underway or have reached accrual await sufficient follow-up for analysis. These studies, which cover a wide range of doses per fraction, should ultimately be capable of validating the utility of prostate hypofractionation and the models that predict its effects. With hypofractionation’s significant potential for therapeutic gain, cost savings and improved patient convenience, the future management of localized prostate cancer could be profoundly altered in the process. PMID:19197165

  12. PSA and beyond: alternative prostate cancer biomarkers

    PubMed Central

    2016-01-01

    Background The use of biomarkers for prostate cancer screening, diagnosis and prognosis has the potential to improve the clinical management of the patients. Owing to inherent limitations of the biomarker prostate-specific antigen (PSA), intensive efforts are currently directed towards a search for alternative prostate cancer biomarkers, particularly those that can predict disease aggressiveness and drive better treatment decisions. Methods A literature search of Medline articles focused on recent and emerging advances in prostate cancer biomarkers was performed. The most promising biomarkers that have the potential to meet the unmet clinical needs in prostate cancer patient management and/or that are clinically implemented were selected. Conclusions With the advent of advanced genomic and proteomic technologies, we have in recent years seen an enormous spurt in prostate cancer biomarker research with several promising alternative biomarkers being discovered that show an improved sensitivity and specificity over PSA. The new generation of biomarkers can be tested via serum, urine, or tissue-based assays that have either received regulatory approval by the US Food and Drug Administration or are available as Clinical Laboratory Improvement Amendments-based laboratory developed tests. Additional emerging novel biomarkers for prostate cancer, including circulating tumor cells, microRNAs and exosomes, are still in their infancy. Together, these biomarkers provide actionable guidance for prostate cancer risk assessment, and are expected to lead to an era of personalized medicine. PMID:26790878

  13. Expression of the cancer-testis antigen BORIS correlates with prostate cancer.

    PubMed

    Cheema, Zubair; Hari-Gupta, Yukti; Kita, Georgia-Xanthi; Farrar, Dawn; Seddon, Ian; Corr, John; Klenova, Elena

    2014-02-01

    BORIS, a paralogue of the transcription factor CTCF, is a member of the cancer-testis antigen (CT) family. BORIS is normally present at high levels in the testis; however it is aberrantly expressed in various tumors and cancer cell lines. The main objectives of this study were to investigate BORIS expression together with sub-cellular localization in both prostate cell lines and tumor tissues, and assess correlations between BORIS and clinical/pathological characteristics. We examined BORIS mRNA expression, protein levels and cellular localization in a panel of human prostate tissues, cancer and benign, together with a panel prostate cell lines. We also compared BORIS levels and localization with clinical/pathological characteristics in prostate tumors. BORIS was detected in all inspected prostate cancer cell lines and tumors, but was absent in benign prostatic hyperplasia. Increased levels of BORIS protein positively correlated with Gleason score, T-stage and androgen receptor (AR) protein levels in prostate tumors. The relationship between BORIS and AR was further highlighted in prostate cell lines by the ability of ectopically expressed BORIS to activate the endogenous AR mRNA and protein. BORIS localization in the nucleus plus cytoplasm was also associated with higher BORIS levels and Gleason score. Detection of BORIS in prostate tumors suggests potential applications of BORIS as a biomarker for prostate cancer diagnosis, as an immunotherapy target and, potentially, a prognostic marker of more aggressive prostate cancer. The ability of BORIS to activate the AR gene indicates BORIS involvement in the growth and development of prostate tumors. © 2013 Wiley Periodicals, Inc.

  14. Repeat polymorphisms in estrogen metabolism genes and prostate cancer risk: results from the Prostate Cancer Prevention Trial

    PubMed Central

    Tang, Li; Yao, Song; Till, Cathee; Goodman, Phyllis J.; Tangen, Catherine M.; Wu, Yue; Kristal, Alan R.; Platz, Elizabeth A.; Neuhouser, Marian L.; Stanczyk, Frank Z.; Reichardt, Juergen K.V.; Santella, Regina M.; Hsing, Ann; Hoque, Ashraful; Lippman, Scott M.; Thompson, Ian M.; Ambrosone, Christine B.

    2011-01-01

    The etiology of prostate cancer remains elusive, although steroid hormones probably play a role. Considering the carcinogenic potential of estrogen metabolites as well as altered intraprostatic estrogen biosynthesis during the development of prostate cancer, we investigated associations between repeat polymorphisms of three key estrogen-related genes (CYP11A1, CYP19A1, UGT1A1) and risk of prostate cancer in the Prostate Cancer Prevention Trial (PCPT), designed to test finasteride versus placebo as a chemoprevention agent. Using data and specimens from 1154 cases and 1351 controls who were frequency matched on age, family history of prostate cancer and PCPT treatment arm, we used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) separately in the placebo and finasteride arms. Among men in the placebo arm, CYP19A1 7/8 genotype carriers had a significantly higher risk of prostate cancer compared with those with the 7/7 genotype (OR = 1.70, 95% CI = 1.16–2.5), regardless of Gleason grade. This genotype was also associated with elevated serum estrogen levels. For the (TA)n repeat polymorphism in UGT1A1, the heterozygous short (<7 repeats)/long (≥7 repeats) genotype was significantly associated with the risk of low-grade prostate cancer (OR = 1.34, 95% CI = 1.05–1.70) compared with the short/short genotype. No significant association was found with CYP11A1. These associations were not observed among men in the finasteride arm. The results indicate that repeat polymorphisms in genes involved in estrogen biosynthesis and metabolism may influence risk of prostate cancer but that their effects may be modified by factors altering hormone metabolism, such as finasteride treatment. PMID:21771722

  15. Syndecan-1-Dependent Suppression of PDK1/Akt/Bad Signaling by Docosahexaenoic Acid Induces Apoptosis in Prostate Cancer1

    PubMed Central

    Hu, Yunping; Sun, Haiguo; Owens, Rick T; Gu, Zhennan; Wu, Jansheng; Chen, Yong Q; O'Flaherty, Joseph T; Edwards, Iris J

    2010-01-01

    Evidence indicates that diets enriched in n-3 polyunsaturated fatty acids (n-3 PUFAs) reduce the risk of prostate cancer, but biochemical mechanisms are unclear. Syndecan-1 (SDC-1), a transmembrane heparan sulfate proteoglycan, supports the integrity of the epithelial compartment. In tumor cells of epithelial lineage, SDC-1 is generally downregulated. This may result in perturbation of homeostasis and lead to progression of malignancy. Our studies have shown that the n-3 PUFA species, docosahexaenoic acid (DHA), increases SDC-1 expression in prostate tissues of Pten knockout (PtenP-/-) mice/cells and human prostate cancer cells. We have now determined that DHA-mediated up-regulation of SDC-1 induces apoptosis. Bovine serum albumin-bound DHA and exogenous human recombinant SDC-1 ecotodomain were delivered to PC3 and LNCaP cells in the presence or absence of SDC-1 small interfering (si)RNA. In the presence of control siRNA, both DHA and SDC-1 ectodomain induced apoptosis, whereas SDC-1 silencing blocked DHA-induced but not SDC-1 ectodomain-induced apoptosis. Downstream effectors of SDC-1 signaling linked to n-3 PUFA-induced apoptosis involved the 3′-phosphoinositide-dependent kinase 1 (PDK1)/Akt/Bad integrating network. A diet enriched in n-3 PUFA decreased phosphorylation of PDK1, Akt (T308), and Bad in prostates of PtenP-/- mice. Similar results were observed in human prostate cancer cells in response to DHA and SDC-1 ectodomain. The effect of DHA on PDK1/Akt/Bad signaling was abrogated by SDC-1 siRNA. These findings define a mechanism by which SDC-1-dependent suppression of phosphorylation of PDK1/Akt/Bad mediates n-3 PUFA-induced apoptosis in prostate cancer. PMID:20927321

  16. Functional Imaging for Prostate Cancer: Therapeutic Implications

    PubMed Central

    Aparici, Carina Mari; Seo, Youngho

    2012-01-01

    Functional radionuclide imaging modalities, now commonly combined with anatomical imaging modalities CT or MRI (SPECT/CT, PET/CT, and PET/MRI) are promising tools for the management of prostate cancer particularly for therapeutic implications. Sensitive detection capability of prostate cancer using these imaging modalities is one issue; however, the treatment of prostate cancer using the information that can be obtained from functional radionuclide imaging techniques is another challenging area. There are not many SPECT or PET radiotracers that can cover the full spectrum of the management of prostate cancer from initial detection, to staging, prognosis predictor, and all the way to treatment response assessment. However, when used appropriately, the information from functional radionuclide imaging improves, and sometimes significantly changes, the whole course of the cancer management. The limitations of using SPECT and PET radiotracers with regards to therapeutic implications are not so much different from their limitations solely for the task of detecting prostate cancer; however, the specific imaging target and how this target is reliably imaged by SPECT and PET can potentially make significant impact in the treatment of prostate cancer. Finally, while the localized prostate cancer is considered manageable, there is still significant need for improvement in noninvasive imaging of metastatic prostate cancer, in treatment guidance, and in response assessment from functional imaging including radionuclide-based techniques. In this review article, we present the rationale of using functional radionuclide imaging and the therapeutic implications for each of radionuclide imaging agent that have been studied in human subjects. PMID:22840598

  17. HUMAN PROSTATE CANCER RISK FACTORS

    EPA Science Inventory

    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...

  18. Defining Young in the Context of Prostate Cancer

    PubMed Central

    Lowe, Anthony; Hyde, Melissa K.; Zajdlewicz, Leah; Gardiner, Robert A.; Sandoe, David; Dunn, Jeff

    2015-01-01

    The experience of prostate cancer is for most men a major life stress with the psychological burden of this disease falling more heavily on those who are younger. Despite this, being young as it applies to prostate cancer is not yet clearly defined with varied chronological approaches applied. However, men’s responses to health crises are closely bound to life course and masculinities from which social roles emerge. This paper applied qualitative methodology (structured focus groups and semistructured interviews with expert informants) using interpretative phenomenological analysis to define what it means to be young and have prostate cancer. Structured focus groups were held with 26 consumer advisors (men diagnosed with prostate cancer who provide support to other men with prostate cancer or raise community awareness) and health professionals. As well, 15 men diagnosed with prostate cancer and in their 40s, 50s, or 60s participated in semi-structured interviews. Participants discussed the attributes that describe a young man with prostate cancer and the experience of being young and diagnosed with prostate cancer. Chronological definitions of a young man were absent or inconsistent. Masculine constructions of what it means to be a young man and life course characteristics appear more relevant to defining young as it applies to prostate cancer compared with chronological age. These findings have implications for better understanding the morbidities associated with this illness, and in designing interventions that are oriented to life course and helping young men reconstruct their identities after prostate cancer. PMID:24780936

  19. COX-2 and Prostate Cancer Angiogenesis

    DTIC Science & Technology

    2001-03-01

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

  20. Prostate Cancer Biorepository Network (PCBN)

    DTIC Science & Technology

    2017-10-01

    Award Number: W81XWH-14-2-0183 TITLE: Prostate Cancer Biorepository Network (PCBN) PRINCIPAL INVESTIGATOR: Colm Morrissey CONTRACTING...1. REPORT DATE October 2017 2. REPORT TYPE Annual 3. DATES COVERED 09/30/2016 - 09/29/2017 4. TITLE AND SUBTITLE Prostate Cancer Biorepository...DISTRIBUTION / AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The Genitourinary Cancer

  1. Validation of a contemporary prostate cancer grading system using prostate cancer death as outcome.

    PubMed

    Berney, Daniel M; Beltran, Luis; Fisher, Gabrielle; North, Bernard V; Greenberg, David; Møller, Henrik; Soosay, Geraldine; Scardino, Peter; Cuzick, Jack

    2016-05-10

    Gleason scoring (GS) has major deficiencies and a novel system of five grade groups (GS⩽6; 3+4; 4+3; 8; ⩾9) has been recently agreed and included in the WHO 2016 classification. Although verified in radical prostatectomies using PSA relapse for outcome, it has not been validated using prostate cancer death as an outcome in biopsy series. There is debate whether an 'overall' or 'worst' GS in biopsies series should be used. Nine hundred and eighty-eight prostate cancer biopsy cases were identified between 1990 and 2003, and treated conservatively. Diagnosis and grade was assigned to each core as well as an overall grade. Follow-up for prostate cancer death was until 31 December 2012. A log-rank test assessed univariable differences between the five grade groups based on overall and worst grade seen, and using univariable and multivariable Cox proportional hazards. Regression was used to quantify differences in outcome. Using both 'worst' and 'overall' GS yielded highly significant results on univariate and multivariate analysis with overall GS slightly but insignificantly outperforming worst GS. There was a strong correlation with the five grade groups and prostate cancer death. This is the largest conservatively treated prostate cancer cohort with long-term follow-up and contemporary assessment of grade. It validates the formation of five grade groups and suggests that the 'worst' grade is a valid prognostic measure.

  2. Prostate cancer-specific mortality and the extent of therapy in healthy elderly men with high-risk prostate cancer.

    PubMed

    Hoffman, Karen E; Chen, Ming-Hui; Moran, Brian J; Braccioforte, Michelle H; Dosoretz, Daniel; Salenius, Sharon; Katin, Michael J; Ross, Rudi; D'Amico, Anthony V

    2010-06-01

    The risk of prostate cancer-specific mortality (PCSM) in healthy elderly men may depend on extent of treatment. The authors of this report compared the use of brachytherapy alone with combined brachytherapy, external-beam radiation to the prostate and seminal vesicles, and androgen-suppression therapy (CMT) in this population. The study cohort comprised 764 men aged > or = 65 years with high-risk prostate cancer (T3 or T4N0M0, prostate-specific antigen >20 ng/mL, and/or Gleason score 8-10) who received either brachytherapy alone (n = 206) or CMT (n = 558) at the Chicago Prostate Cancer Center or at a 21st Century Oncology facility. Men either had no history of myocardial infarction (MI) or had a history of MI treated with a stent or surgical intervention. Fine and Gray regression analysis was used to identify the factors associated with PCSM. The median patient age was 73 years (interquartile range, 70-77 years). After a median follow-up of 4.9 years, 25 men died of prostate cancer. After adjusting for age and prostate cancer prognostic factors, the risk of PCSM was significantly less (adjusted hazard ratio, 0.29; 95% confidence interval, 0.12-0.68; P = .004) for men who received CMT than for men who received brachytherapy alone. Other factors that were associated significantly with an increased risk of PCSM included a Gleason score of 8 to 10 (P = .017). Elderly men who had high-risk prostate cancer without cardiovascular disease or with surgically corrected cardiovascular disease had a lower risk of PCSM when they received CMT than when they received brachytherapy alone. These results support aggressive locoregional treatment in healthy elderly men with high-risk prostate cancer. (c) 2010 American Cancer Society.

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

    PubMed

    Alberts, Arnout R; Schoots, Ivo G; Roobol, Monique J

    2015-06-01

    Prostate-specific antigen-based prostate cancer screening remains a controversial topic. Up to now, there is worldwide consensus on the statement that the harms of population-based screening, mainly as a result of overdiagnosis (the detection of clinically insignificant tumors that would have never caused any symptoms), outweigh the benefits. However, worldwide opportunistic screening takes place on a wide scale. The European Randomized Study of Screening for Prostate Cancer showed a reduction in prostate cancer mortality through prostate-specific antigen based-screening. These population-based data need to be individualized in order to avoid screening in those who cannot benefit and start screening in those who will. For now, lacking a more optimal screening approach, screening should only be started after the process of shared decision-making. The focus of future research is the reduction of unnecessary testing and overdiagnosis by further research to better biomarkers and the value of the multiparametric magnetic resonance imaging, potentially combined in already existing prostate-specific antigen-based multivariate risk prediction models. © 2015 The Japanese Urological Association.

  4. sEphB4-HSA Before Surgery in Treating Patients With Bladder Cancer, Prostate Cancer, or Kidney Cancer

    ClinicalTrials.gov

    2018-06-08

    Infiltrating Bladder Urothelial Carcinoma; Recurrent Bladder Carcinoma; Stage I Prostate Cancer; Stage I Renal Cell Cancer; Stage II Bladder Urothelial Carcinoma; Stage II Renal Cell Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer

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

    PubMed

    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.

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

    DTIC Science & Technology

    2016-10-01

    INVESTIGATOR: Wendy Huss, PhD CONTRACTING ORGANIZATION : Health Research , Inc. Buffalo, NY 14263-0001 REPORT DATE: October 2016 TYPE OF REPORT: Annual...RHPCS Program to encourage interns to enter graduate training and careers in prostate cancer research . Completion dates for activities and progress on... interns to enter graduate training and careers in prostate cancer research . SOW-Major Task 4: Track Prostate Cancer Scholar professional activities

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

    PubMed

    Lokant, M T; Naz, R K

    2015-04-01

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

  8. Prostate cancer stem cells: from theory to practice.

    PubMed

    Adamowicz, Jan; Pakravan, Katayoon; Bakhshinejad, Babak; Drewa, Tomasz; Babashah, Sadegh

    2017-04-01

    None of the generally accepted theories on prostate cancer development can fully explain many distinguishing features of the disease, such as intratumoral heterogeneity, metastatic growth, drug resistance and tumor relapse. Prostate stem cells are a heterogeneous and small subpopulation of self-renewing cells which can actively proliferate in response to changes in the androgen level and give rise to all the cell lineages that build the prostate epithelium. According to the cancer stem cell hypothesis, prostate cancer could be a stem cell disease. Prostate cancer stem cells, which represent only a minimal percentage of the tumor mass, are characterized by a markedly increased clonogenicity and therapeutic resistance. These tumor-initiating cells reside in dynamic niches distributed within the prostate but at a higher concentration in proximal regions of the prostatic ducts. Several markers have been used to identify prostate cancer stem cells. Nevertheless, a definitive profile has not yet been established owing to specificity issues. As cancer stem cells play determining roles in the birth and burst of prostate malignancy, strategies that selectively target them have gained huge clinical attention. Unraveling the mechanisms underlying the physiological functions of cancer stem cells and gaining fundamental insights into their putative involvement in the pathogenesis of prostate tumors provide novel opportunities for the development of efficient and sophisticated therapeutic strategies in the future.

  9. A genome-wide pleiotropy scan for prostate cancer risk.

    PubMed

    Panagiotou, Orestis A; Travis, Ruth C; Campa, Daniele; Berndt, Sonja I; Lindstrom, Sara; Kraft, Peter; Schumacher, Fredrick R; Siddiq, Afshan; Papatheodorou, Stefania I; Stanford, Janet L; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie J; Diver, W Ryan; Gapstur, Susan M; Stevens, Victoria L; Boeing, Heiner; Bueno-de-Mesquita, H Bas; Barricarte Gurrea, Aurelio; Kaaks, Rudolf; Khaw, Kay-Tee; Krogh, Vittorio; Overvad, Kim; Riboli, Elio; Trichopoulos, Dimitrios; Giovannucci, Edward; Stampfer, Meir; Haiman, Christopher; Henderson, Brian; Le Marchand, Loic; Gaziano, J Michael; Hunter, David J; Koutros, Stella; Yeager, Meredith; Hoover, Robert N; Chanock, Stephen J; Wacholder, Sholom; Key, Timothy J; Tsilidis, Konstantinos K

    2015-04-01

    No single-nucleotide polymorphisms (SNPs) specific for aggressive prostate cancer have been identified in genome-wide association studies (GWAS). To test if SNPs associated with other traits may also affect the risk of aggressive prostate cancer. SNPs implicated in any phenotype other than prostate cancer (p≤10(-7)) were identified through the catalog of published GWAS and tested in 2891 aggressive prostate cancer cases and 4592 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). The 40 most significant SNPs were followed up in 4872 aggressive prostate cancer cases and 24,534 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Odds ratios (ORs) and 95% confidence intervals (CIs) for aggressive prostate cancer were estimated. A total of 4666 SNPs were evaluated by the BPC3. Two signals were seen in regions already reported for prostate cancer risk. rs7014346 at 8q24.21 was marginally associated with aggressive prostate cancer in the BPC3 trial (p=1.6×10(-6)), whereas after meta-analysis by PRACTICAL the summary OR was 1.21 (95% CI 1.16-1.27; p=3.22×10(-18)). rs9900242 at 17q24.3 was also marginally associated with aggressive disease in the meta-analysis (OR 0.90, 95% CI 0.86-0.94; p=2.5×10(-6)). Neither of these SNPs remained statistically significant when conditioning on correlated known prostate cancer SNPs. The meta-analysis by BPC3 and PRACTICAL identified a third promising signal, marked by rs16844874 at 2q34, independent of known prostate cancer loci (OR 1.12, 95% CI 1.06-1.19; p=4.67×10(-5)); it has been shown that SNPs correlated with this signal affect glycine concentrations. The main limitation is the heterogeneity in the definition of aggressive prostate cancer between BPC3 and PRACTICAL. We did not identify new SNPs for aggressive prostate cancer. However, rs16844874 may provide preliminary genetic evidence on the role of the glycine pathway in

  10. Prostate cancer - treatment

    MedlinePlus

    ... usually painless. Treatment is done in a radiation oncology center that is usually connected to a hospital. ... Cancer Network website. NCCN clinical practice guidelines in oncology (NCCN guidelines): prostate cancer. Version 2.2017. www. ...

  11. Prostate cancer staging

    MedlinePlus

    ... test. A faster increase could show a more aggressive tumor. A prostate biopsy is done in your ... suggest the cancer is slow growing and not aggressive. Higher numbers indicate a faster growing cancer that ...

  12. Lipid degradation promotes prostate cancer cell survival.

    PubMed

    Itkonen, Harri M; Brown, Michael; Urbanucci, Alfonso; Tredwell, Gregory; Ho Lau, Chung; Barfeld, Stefan; Hart, Claire; Guldvik, Ingrid J; Takhar, Mandeep; Heemers, Hannelore V; Erho, Nicholas; Bloch, Katarzyna; Davicioni, Elai; Derua, Rita; Waelkens, Etienne; Mohler, James L; Clarke, Noel; Swinnen, Johan V; Keun, Hector C; Rekvig, Ole P; Mills, Ian G

    2017-06-13

    Prostate cancer is the most common male cancer and androgen receptor (AR) is the major driver of the disease. Here we show that Enoyl-CoA delta isomerase 2 (ECI2) is a novel AR-target that promotes prostate cancer cell survival. Increased ECI2 expression predicts mortality in prostate cancer patients (p = 0.0086). ECI2 encodes for an enzyme involved in lipid metabolism, and we use multiple metabolite profiling platforms and RNA-seq to show that inhibition of ECI2 expression leads to decreased glucose utilization, accumulation of fatty acids and down-regulation of cell cycle related genes. In normal cells, decrease in fatty acid degradation is compensated by increased consumption of glucose, and here we demonstrate that prostate cancer cells are not able to respond to decreased fatty acid degradation. Instead, prostate cancer cells activate incomplete autophagy, which is followed by activation of the cell death response. Finally, we identified a clinically approved compound, perhexiline, which inhibits fatty acid degradation, and replicates the major findings for ECI2 knockdown. This work shows that prostate cancer cells require lipid degradation for survival and identifies a small molecule inhibitor with therapeutic potential.

  13. Emerging Therapies in Metastatic Prostate Cancer.

    PubMed

    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.

  14. Are strict vegetarians protected against prostate cancer?

    PubMed

    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.

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

    Cancer.gov

    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

  16. Epidemiology of prostate cancer in Asian countries.

    PubMed

    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.

  17. Phospholipase PLA2G7, associated with aggressive prostate cancer, promotes prostate cancer cell migration and invasion and is inhibited by statins

    PubMed Central

    Vainio, Paula; Lehtinen, Laura; Mirtti, Tuomas; Hilvo, Mika; Seppänen-Laakso, Tuulikki; Virtanen, Johannes; Sankila, Anna; Nordling, Stig; Lundin, Johan; Rannikko, Antti; Orešič, Matej; Kallioniemi, Olli; Iljin, Kristiina

    2011-01-01

    Prostate cancer is the second leading cause of cancer mortality in men in developed countries. Due to the heterogeneous nature of the disease, design of novel personalized treatments is required to achieve efficient therapeutic responses. We have recently identified phospholipase 2 group VII (PLA2G7) as a potential drug target especially in ERG oncogene positive prostate cancers. Here, the expression profile of PLA2G7 was studied in 1137 prostate cancer and 409 adjacent non-malignant prostate tissues using immunohistochemistry to validate its biomarker potential and putative association with disease progression. In order to reveal the molecular alterations induced by PLA2G7 impairment, lipidomic and gene expression profiling was performed in response to PLA2G7 silencing in cultured prostate cancer cells. Moreover, the antineoplastic effect of statins combined with PLA2G7 impairment was studied in prostate cancer cells to evaluate the potential of repositioning of in vivo compatible drugs developed for other indications towards anti-cancer purposes. The results indicated that PLA2G7 is a cancer-selective biomarker in 50% of prostate cancers and associates with aggressive disease. The alterations induced by PLA2G7 silencing highlighted the potential of PLA2G7 inhibition as an anti-proliferative, pro-apoptotic and anti-migratorial therapeutic approach in prostate cancer. Moreover, the anti-proliferative effect of PLA2G7 silencing was potentiated by lipid-lowering statins in prostate cancer cells. Taken together, our results support the potential of PLA2G7 as a biomarker and a drug target in prostate cancer and present a rationale for combining PLA2G7 inhibition with the use of statins in prostate cancer management. PMID:22202492

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

    PubMed

    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.

  19. Tocotrienols and Prostate Cancer

    DTIC Science & Technology

    2005-09-01

    W81XWH-04-1-0035 TITLE: Tocotrienols and Prostate Cancer PRINCIPAL INVESTIGATOR: William L. Stone, Ph.D...REPORT DATE (DD-MM-YYYY) September 2005 2. REPORT TYPE Final 3. DATES COVERED (From - To) 1 Mar 04 – 31 AUG 05 5a. CONTRACT NUMBER Tocotrienols ...tocopherols and tocotrienols , have variable growth inhibitory effects on both types of prostate cancer cell line models. The gamma isoforms are more

  20. Abiraterone acetate in the treatment of prostate cancer.

    PubMed

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

    2018-05-01

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

  1. Emerging Vaccine Therapy Approaches for Prostate Cancer

    PubMed Central

    Sonpavde, Guru; Slawin, Kevin M; Spencer, David M; Levitt, Jonathan M

    2010-01-01

    Prostate cancer vaccines attempt to induce clinically relevant, cancer-specific systemic immune responses in patients with prostate cancer and represent a new class of targeted, nontoxic therapies. With a growing array of vaccine technologies in preclinical or clinical development, autologous antigen-presenting cell vaccines loaded with the antigen, prostate acid phosphatase, and poxvirus vaccines targeting prostate-specific antigen have recently demonstrated a significant survival benefit in randomized trials of patients with metastatic castration-resistant prostate cancer, whereas others have failed to demonstrate any benefit. The combination of vaccines with chemotherapy, radiotherapy, and other biologic agents is also being evaluated. Efforts to optimize vaccine approaches and select ideal patient populations need to continue to build on these early successes. PMID:20428291

  2. Genome scan study of prostate cancer in Arabs: identification of three genomic regions with multiple prostate cancer susceptibility loci in Tunisians.

    PubMed

    Shan, Jingxuan; Al-Rumaihi, Khalid; Rabah, Danny; Al-Bozom, Issam; Kizhakayil, Dhanya; Farhat, Karim; Al-Said, Sami; Kfoury, Hala; Dsouza, Shoba P; Rowe, Jillian; Khalak, Hanif G; Jafri, Shahzad; Aigha, Idil I; Chouchane, Lotfi

    2013-05-13

    Large databases focused on genetic susceptibility to prostate cancer have been accumulated from population studies of different ancestries, including Europeans and African-Americans. Arab populations, however, have been only rarely studied. Using Affymetrix Genome-Wide Human SNP Array 6, we conducted a genome-wide association study (GWAS) in which 534,781 single nucleotide polymorphisms (SNPs) were genotyped in 221 Tunisians (90 prostate cancer patients and 131 age-matched healthy controls). TaqMan SNP Genotyping Assays on 11 prostate cancer associated SNPs were performed in a distinct cohort of 337 individuals from Arab ancestry living in Qatar and Saudi Arabia (155 prostate cancer patients and 182 age-matched controls). In-silico expression quantitative trait locus (eQTL) analysis along with mRNA quantification of nearby genes was performed to identify loci potentially cis-regulated by the identified SNPs. Three chromosomal regions, encompassing 14 SNPs, are significantly associated with prostate cancer risk in the Tunisian population (P = 1 × 10-4 to P = 1 × 10-5). In addition to SNPs located on chromosome 17q21, previously found associated with prostate cancer in Western populations, two novel chromosomal regions are revealed on chromosome 9p24 and 22q13. eQTL analysis and mRNA quantification indicate that the prostate cancer associated SNPs of chromosome 17 could enhance the expression of STAT5B gene. Our findings, identifying novel GWAS prostate cancer susceptibility loci, indicate that prostate cancer genetic risk factors could be ethnic specific.

  3. Radioligand therapy of metastatic castration-resistant prostate cancer: current approaches.

    PubMed

    Awang, Zool Hilmi; Essler, Markus; Ahmadzadehfar, Hojjat

    2018-05-23

    Prostate Cancer is the forth most common type of cancer. Prostate-specific membrane antigen (PSMA) is anchored in the cell membrane of prostate epithelial cells. PSMA is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer. Therefore it is an appropriate target for diagnostic and therapy of prostate cancer and its metastases. This article discusses several articles on radionuclide treatments in prostate cancer and the results on PSMA therapy with either beta or alpha emitters as a salvage therapy.

  4. Validation of a contemporary prostate cancer grading system using prostate cancer death as outcome

    PubMed Central

    Berney, Daniel M; Beltran, Luis; Fisher, Gabrielle; North, Bernard V; Greenberg, David; Møller, Henrik; Soosay, Geraldine; Scardino, Peter; Cuzick, Jack

    2016-01-01

    Background: Gleason scoring (GS) has major deficiencies and a novel system of five grade groups (GS⩽6; 3+4; 4+3; 8; ⩾9) has been recently agreed and included in the WHO 2016 classification. Although verified in radical prostatectomies using PSA relapse for outcome, it has not been validated using prostate cancer death as an outcome in biopsy series. There is debate whether an ‘overall' or ‘worst' GS in biopsies series should be used. Methods: Nine hundred and eighty-eight prostate cancer biopsy cases were identified between 1990 and 2003, and treated conservatively. Diagnosis and grade was assigned to each core as well as an overall grade. Follow-up for prostate cancer death was until 31 December 2012. A log-rank test assessed univariable differences between the five grade groups based on overall and worst grade seen, and using univariable and multivariable Cox proportional hazards. Regression was used to quantify differences in outcome. Results: Using both ‘worst' and ‘overall' GS yielded highly significant results on univariate and multivariate analysis with overall GS slightly but insignificantly outperforming worst GS. There was a strong correlation with the five grade groups and prostate cancer death. Conclusions: This is the largest conservatively treated prostate cancer cohort with long-term follow-up and contemporary assessment of grade. It validates the formation of five grade groups and suggests that the ‘worst' grade is a valid prognostic measure. PMID:27100731

  5. Macrophage Efferocytosis and Prostate Cancer Bone Metastasis

    DTIC Science & Technology

    2015-10-01

    prostate cancer bone metastasis through the phagocytosis of apoptotic tumor cells (efferocytosis). Specific Aims: 1. To identify the phagocytic ...2: To identify the phagocytic /efferocytic macrophage population in the tumor microenvironment of prostate bone metastases and determine its ability...preparation for Cancer Research. We obtained an array of prostate cancer tissue including bone metastasis (N=72) and stained the tissue for the phagocytic

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

    PubMed

    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.

  7. Combining immunotherapies for the treatment of prostate cancer.

    PubMed

    Redman, Jason M; Gulley, James L; Madan, Ravi A

    2017-12-01

    Sipuleucel-T, a therapeutic dendritic-cell vaccine, was Food and Drug Administration-approved for prostate cancer in 2010. No new immunotherapies for prostate cancer have been approved since. However, novel agents and combination approaches offer great promise for improving outcomes for prostate cancer patients. Here we review the latest developments in immunotherapy for prostate cancer. Sipuleucel-T has demonstrated a survival advantage of 4.1 months in metastatic castration-resistant prostate cancer. PSA-TRICOM (PROSTVAC), a prostate-specific antigen-targeted vaccine platform, showed evidence of clinical and immunologic efficacy in early-phase clinical trials, and results from a phase III trial in advanced disease are pending. While immune checkpoint inhibitors appear to have modest activity as monotherapy, preclinical and clinical data suggest that they may synergize with vaccines, poly [ADP-ribose] polymerase inhibitors, and other agents. Several clinical studies that combine these therapies are underway. Combining prostate cancer vaccines with immune checkpoint inhibitors has great potential for improving clinical outcomes in prostate cancer. Such combination approaches may create and then recruit tumor-specific T cells to tumor while also increasing their effector function. Other emerging agents may also enhance immune-mediated tumor destruction. Copyright © 2017. Published by Elsevier Inc.

  8. New treatments for localized prostate cancer.

    PubMed

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

    2008-12-01

    Interest in focal therapy for prostate cancer has recently been renewed owing to downward stage migration, improved biopsy and imaging techniques, and the prevalence of either unifocal cancer or a dominant cancer with secondary tumors of minimal malignant potential. Several techniques have potential for focal ablation of prostate cancer. Cryotherapy has been used for some time as primary therapy for complete ablation of the prostate or local recurrence after radiotherapy. Enthusiasm for cryotherapy as the primary therapy has been tempered by the uncertainty about complete ablation of the cancer, the frequent persistence of measurable prostate-specific antigen levels after the procedure, and a high rate of erectile dysfunction. Studies have reported "focal ablation" of prostate cancer with cryotherapy, targeting 1 side of the gland to eliminate a cancer confined to that side with less risk of urinary or sexual complications. Whether cryotherapy has sufficient power to eradicate focal cancer and can be targeted with sufficient accuracy to avoid damage to surrounding structures remains to be demonstrated in prospective clinical trials. High-intensity focused ultrasound (HIFU) has been used widely in Europe for complete ablation of the prostate, especially in elderly men who are unwilling or unable to undergo radical therapy. For low- or intermediate-risk cancer, the short- and intermediate-term oncologic results have been acceptable but need confirmation in prospective multicenter trials presently underway. Whole gland therapy with transrectal ultrasound guidance has been associated with a high risk of acute urinary symptoms, often requiring transurethral resection before or after HIFU. Adverse effects on erectile function seem likely after a therapy that depends on heat to eradicate the cancer, but erectile function after HIFU has not been adequately documented with patient-reported questionnaires. HIFU holds promise for focal ablation of prostate cancer. As with

  9. Prostate Cancer Probability Prediction By Machine Learning Technique.

    PubMed

    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.

  10. The path forward in prostate cancer therapeutics

    PubMed Central

    Aragon-Ching, Jeanny B; Madan, Ravi A

    2018-01-01

    The last decade has seen remarkable advances in the treatment of prostate cancer. Until 2010, only docetaxel had demonstrated the ability to improve the survival in metastatic castration-resistant prostate cancer (mCRPC).1 While effective, many men were reluctant to get treatment with docetaxel because of the perceived toxicity, thereby further limiting the benefit of the one available and effective therapy. Remarkably, within the last 8 years, the field has seen a multitude of therapies that demonstrate an ability to extend survival for men with prostate cancer. Abiraterone and enzalutamide demonstrated the importance of the androgen axis in propelling prostate cancer growth.23 Sipuleucel-T was immunotherapy's entry into the evolving prostate cancer armamentarium, as the therapeutic cancer vaccine established an ability to extend survival despite an apparent lack of short-term effect on progression-free survival and prostate-specific antigen (PSA).4 Radium-223 built on the palliative success of previous radiopharmaceuticals, but this alpha-emitting agent importantly had limited hematologic-related toxicity and was associated with a survival advantage, unlike its in-class predecessors.5 Cabazitaxel also emerged as a second-line chemotherapy option in patients who had already progressed on docetaxel.6 PMID:29536949

  11. Calcium, magnesium, and whole-milk intakes and high-aggressive prostate cancer in the North Carolina-Louisiana Prostate Cancer Project (PCaP).

    PubMed

    Steck, Susan E; Omofuma, Omonefe O; Su, L Joseph; Maise, Amanda A; Woloszynska-Read, Anna; Johnson, Candace S; Zhang, Hongmei; Bensen, Jeannette T; Fontham, Elizabeth T H; Mohler, James L; Arab, Lenore

    2018-05-01

    Calcium and dairy product intakes have been positively associated with prostate cancer risk. An imbalance in concentrations of calcium and magnesium has been associated with multiple chronic diseases, although few studies have examined the relation with prostate cancer aggressiveness. The goal of this study was to examine the association between dietary intakes of calcium and magnesium, the calcium-to-magnesium ratio (Ca:Mg), and dairy products and prostate cancer aggressiveness. Dietary intake was assessed with the use of an interviewer-administered modified National Cancer Institute Diet History Questionnaire in 996 African American and 1064 European American men with a recent histologically confirmed diagnosis of prostate cancer from the North Carolina-Louisiana Prostate Cancer Project (PCaP). High-aggressive disease was defined as Gleason sum ≥8, or prostate-specific antigen (PSA) >20 ng/mL, or Gleason score ≥7 and clinical stage T3-T4. The comparison group was all other prostate cancer cases. Logistic regression was used to determine the adjusted ORs and 95% CIs for high-aggressive prostate cancer by tertile of diet and supplement exposures. There was a positive association across tertiles of dietary Ca:Mg intake, with odds of high-aggressive prostate cancer in the upper tertiles as follows-OR for tertile 2 compared with tertile 1: 1.38 (95% CI: 1.01, 1.88); OR for tertile 3 compared with tertile 1: 1.46 (95% CI: 1.06, 2.02). When stratified by race, the positive association was more pronounced in African American men (OR for tertile 3 compared with tertile 2: 1.62; 95% CI: 1.04, 2.53). Men who reported the highest daily consumption of whole-fat milk had a 74% increased odds of high-aggressive prostate cancer compared with non-whole-fat milk drinkers, which was attenuated after adjustment for potential mediating factors, such as saturated fat and Ca:Mg intake. Among both African American and European American men diagnosed with prostate cancer, a higher Ca

  12. Behavioral stress accelerates prostate cancer development in mice

    PubMed Central

    Hassan, Sazzad; Karpova, Yelena; Baiz, Daniele; Yancey, Dana; Pullikuth, Ashok; Flores, Anabel; Register, Thomas; Cline, J. Mark; D’Agostino, Ralph; Danial, Nika; Datta, Sandeep Robert; Kulik, George

    2013-01-01

    Prostate cancer patients have increased levels of stress and anxiety. Conversely, men who take beta blockers, which interfere with signaling from the stress hormones adrenaline and noradrenaline, have a lower incidence of prostate cancer; however, the mechanisms underlying stress–prostate cancer interactions are unknown. Here, we report that stress promotes prostate carcinogenesis in mice in an adrenaline-dependent manner. Behavioral stress inhibited apoptosis and delayed prostate tumor involution both in phosphatase and tensin homolog–deficient (PTEN-deficient) prostate cancer xenografts treated with PI3K inhibitor and in prostate tumors of mice with prostate-restricted expression of c-MYC (Hi-Myc mice) subjected to androgen ablation therapy with bicalutamide. Additionally, stress accelerated prostate cancer development in Hi-Myc mice. The effects of stress were prevented by treatment with the selective β2-adrenergic receptor (ADRB2) antagonist ICI118,551 or by inducible expression of PKA inhibitor (PKI) or of BCL2-associated death promoter (BAD) with a mutated PKA phosphorylation site (BADS112A) in xenograft tumors. Effects of stress were also blocked in Hi-Myc mice expressing phosphorylation-deficient BAD (BAD3SA). These results demonstrate interactions between prostate tumors and the psychosocial environment mediated by activation of an adrenaline/ADRB2/PKA/BAD antiapoptotic signaling pathway. Our findings could be used to identify prostate cancer patients who could benefit from stress reduction or from pharmacological inhibition of stress-induced signaling. PMID:23348742

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

    PubMed Central

    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

  14. Multidisciplinary intervention of early, lethal metastatic prostate cancer: Report from the 2015 Coffey-Holden Prostate Cancer Academy Meeting.

    PubMed

    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

    2016-02-01

    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. 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. 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. 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. © 2015 Wiley Periodicals, Inc.

  15. Micrornas in prostate cancer: an overview

    PubMed Central

    Rossetti, Sabrina; Cavaliere, Carla; D'Aniello, Carmine; Di Franco, Rossella; Romano, Francesco Jacopo; Montanari, Micaela; La Mantia, Elvira; Piscitelli, Raffaele; Nocerino, Flavia; Cappuccio, Francesca; Grimaldi, Giovanni; Izzo, Alessandro; Castaldo, Luigi; Pepe, Maria Filomena; Malzone, Maria Gabriella; Iovane, Gelsomina; Ametrano, Gianluca; Stiuso, Paola; Quagliuolo, Lucio; Barberio, Daniela; Perdonà, Sisto; Muto, Paolo; Montella, Maurizio; Maiolino, Piera; Veneziani, Bianca Maria; Botti, Gerardo; Caraglia, Michele; Facchini, Gaetano

    2017-01-01

    Prostate cancer is the second highest cause of cancer mortality after lung tumours. In USA it affects about 2.8 million men and the incidence increases with age in many countries. Therefore, early diagnosis is a very important step for patient clinical evaluation and for a selective and efficient therapy. The study of miRNAs' functions and molecular mechanisms has brought new knowledge in biological processes of cancer. In prostate cancer there is a deregulation of several miRNAs that may function as tumour suppressors or oncogenes. The aim of this review is to analyze the progress made to our understanding of the role of miRNA dysregulation in prostate cancer tumourigenesis. PMID:28445135

  16. Micrornas in prostate cancer: an overview.

    PubMed

    Vanacore, Daniela; Boccellino, Mariarosaria; Rossetti, Sabrina; Cavaliere, Carla; D'Aniello, Carmine; Di Franco, Rossella; Romano, Francesco Jacopo; Montanari, Micaela; La Mantia, Elvira; Piscitelli, Raffaele; Nocerino, Flavia; Cappuccio, Francesca; Grimaldi, Giovanni; Izzo, Alessandro; Castaldo, Luigi; Pepe, Maria Filomena; Malzone, Maria Gabriella; Iovane, Gelsomina; Ametrano, Gianluca; Stiuso, Paola; Quagliuolo, Lucio; Barberio, Daniela; Perdonà, Sisto; Muto, Paolo; Montella, Maurizio; Maiolino, Piera; Veneziani, Bianca Maria; Botti, Gerardo; Caraglia, Michele; Facchini, Gaetano

    2017-07-25

    Prostate cancer is the second highest cause of cancer mortality after lung tumours. In USA it affects about 2.8 million men and the incidence increases with age in many countries. Therefore, early diagnosis is a very important step for patient clinical evaluation and for a selective and efficient therapy. The study of miRNAs' functions and molecular mechanisms has brought new knowledge in biological processes of cancer. In prostate cancer there is a deregulation of several miRNAs that may function as tumour suppressors or oncogenes. The aim of this review is to analyze the progress made to our understanding of the role of miRNA dysregulation in prostate cancer tumourigenesis.

  17. Influence of the neural microenvironment on prostate cancer.

    PubMed

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

    2018-02-01

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

  18. Beyond immune checkpoint blockade: new approaches to targeting host-tumor interactions in prostate cancer: report from the 2014 Coffey-Holden prostate cancer academy meeting.

    PubMed

    Miyahira, Andrea K; Kissick, Haydn T; Bishop, Jennifer L; Takeda, David Y; Barbieri, Christopher E; Simons, Jonathan W; Pienta, Kenneth J; Soule, Howard R

    2015-03-01

    The 2014 Coffey-Holden Prostate Cancer Academy Meeting, held in La Jolla, CA from June 26 to 29, 2014, was themed: "Beyond Immune Checkpoint Blockade: New Approaches to Targeting Host-Tumor Interactions in Prostate Cancer." Sponsored by the Prostate Cancer Foundation (PCF), this annual, invitation-only meeting is structured as an action-tank, and brought together 72 investigators with diverse academic backgrounds to discuss the most relevant topics in the fields of prostate cancer immunotherapy and the tumor microenvironment. The questions addressed at the meeting included: mechanisms underlying the successes and failures of prostate cancer immunotherapies, how to trigger an effective immune response against prostate cancer, the tumor microenvironment and its role in therapy resistance and tumor metastasis, clinically relevant prostate cancer mouse models, how host-tumor interactions affect current therapies and tumor phenotypes, application of principles of precision medicine to prostate cancer immunotherapy, optimizing immunotherapy clinical trial design, and complex multi-system interactions that affect prostate cancer and immune responses including the effects of obesity and the potential role of the host microbiome. This article highlights the most significant recent progress and unmet needs that were discussed at the meeting toward the goal of speeding the development of optimal immunotherapies for the treatment of prostate cancer. © 2014 Wiley Periodicals, Inc.

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

    Cancer.gov

    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 of tumor cells that can self-renew and give rise to more differentiated tumor cells. It is thought that these stem cells survive initial therapies (such as chemotherapy and hormone therapy) and then generate new tumor cells that are resistant to these standard treatments. If prostate cancer stem cells could be identified and characterized, it might be possible to design treatments that prevent resistance.

  20. Minimally invasive treatment for localized prostate cancer.

    PubMed

    Porres, D; Pfister, D; Heidenreich, A

    2012-12-01

    The vast majority of men newly diagnosed with prostate cancer have clinically localized disease. Besides active surveillance in low risk cancers and open radical prostatectomy as the traditional gold standard more and more patients demand a effective tumor control through a minimally invasive approach. After the introduction of laparoscopy for the treatment of prostate cancer especially the robot-assisted radical prostatectomy gained in importance. In recent years the accuracy for cancer localisation within the prostate was considerably improved, which enables the increasing use of focal therapy techniques. In addition to the robot-assisted and conventional laparoscopic radical prostatectomy the current and future importance of cryotherapy, HIFU and vascular targeted photodynamic therapy for localized prostate cancer will be analyzed in the following review article.

  1. Substantial Family History of Prostate Cancer in Black Men Recruited for Prostate Cancer Screening

    PubMed Central

    Mastalski, Kathleen; Coups, Elliot J.; Ruth, Karen; Raysor, Susan; Giri, Veda N.

    2008-01-01

    Background Black men are at increased risk for prostate cancer (PCA), particularly with a family history (FH) of the disease. Previous reports have raised concern for suboptimal screening of Black men with a FH of PCA. We report on the extent of FH of PCA from a prospective, longitudinal PCA screening program for high-risk men. Methods Black men ages 35-69 are eligible for PCA screening through the Prostate Cancer Risk Assessment Program (PRAP) regardless of FH. Rates of self-reported FH of PCA, breast, and colon cancer at baseline were compared with an age-matched sample of Black men from the 2005 National Health Interview Survey (NHIS) using standard statistical methods. Results As of January 2007, 332 Black men with pedigree information were enrolled in PRAP and FH of PCA was compared to 838 Black men from the 2005 NHIS. Black men in PRAP reported significantly more first-degree relatives with PCA compared to Black men in the 2005 NHIS (34.3%, 95% CI 29.2-39.7 vs. 5.7%, 95% CI 3.9-7.4). Black men in PRAP also had more FH of breast cancer compared to the 2005 NHIS (11.5%, 95% CI 8.2-15.4 vs 6.3%, 95% CI 4.6-8.0). Conclusions FH of PCA appears to be a motivating factor for Black men seeking PCA screening. Targeted recruitment and education among Black families should improve PCA screening rates. Efforts to recruit Black men without a FH of PCA are also needed. Condensed Abstract Black men seeking prostate cancer screening have a substantial burden of family history of prostate cancer. Targeted education and enhancing discussion in Black families should increase prostate cancer screening and adherence. PMID:18816608

  2. Internet-Based Education for Prostate Cancer Screening

    DTIC Science & Technology

    2007-12-01

    BPH) BPH is enlargement of the prostate. BPH is not cancer. The prostate tends to increase in size as men get older. This can cause the urethra to... enlarged . But I still worry sometimes that I might have cancer. I often wonder whether this PSA test has helped me at all. 11 T R E A T M E N T IS S U E... enlarged prostate. • This approach increases the risk that a cancer might be overlooked in a man with an enlarged prostate. • Therefore, the use of PSA

  3. Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients.

    PubMed

    Schlick, Bettina; Massoner, Petra; Lueking, Angelika; Charoentong, Pornpimol; Blattner, Mirjam; Schaefer, Georg; Marquart, Klaus; Theek, Carmen; Amersdorfer, Peter; Zielinski, Dirk; Kirchner, Matthias; Trajanoski, Zlatko; Rubin, Mark A; Müllner, Stefan; Schulz-Knappe, Peter; Klocker, Helmut

    2016-01-01

    Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens. Radical prostatectomy specimens of prostate cancer patients (N = 70) were classified into high and low inflammation groups according to the amount of tissue infiltrating lymphocytes. The corresponding pre-surgery blood serum samples were scrutinized for autoantibodies using a low-density protein array. Selected autoantigens were identified in prostate tissue and their expression pattern analyzed by immunohistochemistry and qPCR. The identified autoantibody profile was cross-checked in an independent sample set (N = 63) using the Luminex-bead protein array technology. Protein array screening identified 165 autoantibodies differentially abundant in the serum of high compared to low inflammation patients. The expression pattern of three corresponding antigens were established in benign and cancer tissue by immunohistochemistry and qPCR: SPAST (Spastin), STX18 (Syntaxin 18) and SPOP (speckle-type POZ protein). Of these, SPAST was significantly increased in prostate tissue with high inflammation. All three autoantigens were differentially expressed in primary and/or castration resistant prostate tumors when analyzed in an inflammation-independent tissue microarray. Cross-validation of the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array, retrieved 51 of the significantly discriminating autoantibodies. Three autoantibodies were significantly upregulated in both screens, MUT, RAB11B and CSRP2 (p>0

  4. Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients

    PubMed Central

    Schlick, Bettina; Massoner, Petra; Lueking, Angelika; Charoentong, Pornpimol; Blattner, Mirjam; Schaefer, Georg; Marquart, Klaus; Theek, Carmen; Amersdorfer, Peter; Zielinski, Dirk; Kirchner, Matthias; Trajanoski, Zlatko; Rubin, Mark A.; Müllner, Stefan; Schulz-Knappe, Peter; Klocker, Helmut

    2016-01-01

    Background Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens. Methods Radical prostatectomy specimens of prostate cancer patients (N = 70) were classified into high and low inflammation groups according to the amount of tissue infiltrating lymphocytes. The corresponding pre-surgery blood serum samples were scrutinized for autoantibodies using a low-density protein array. Selected autoantigens were identified in prostate tissue and their expression pattern analyzed by immunohistochemistry and qPCR. The identified autoantibody profile was cross-checked in an independent sample set (N = 63) using the Luminex-bead protein array technology. Results Protein array screening identified 165 autoantibodies differentially abundant in the serum of high compared to low inflammation patients. The expression pattern of three corresponding antigens were established in benign and cancer tissue by immunohistochemistry and qPCR: SPAST (Spastin), STX18 (Syntaxin 18) and SPOP (speckle-type POZ protein). Of these, SPAST was significantly increased in prostate tissue with high inflammation. All three autoantigens were differentially expressed in primary and/or castration resistant prostate tumors when analyzed in an inflammation-independent tissue microarray. Cross-validation of the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array, retrieved 51 of the significantly discriminating autoantibodies. Three autoantibodies were significantly upregulated in both screens, MUT

  5. 78 FR 54745 - National Prostate Cancer Awareness Month, 2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-06

    ... National Prostate Cancer Awareness Month, 2013 By the President of the United States of America A Proclamation Among American men, prostate cancer is both the second most commonly diagnosed cancer and the second-leading cause of cancer deaths. Although prostate cancer incidence and mortality rates have...

  6. How Precisely Can Prostate Cancer Be Managed?

    PubMed Central

    2016-01-01

    Progress has been made in applying genetic information to disease management in the postgenomic era, and precision medicine is emerging in prostate cancer management. The prostate health index, the 4-kallikrein (4K) score, and the PCA3, TMPRSS2-ERG, and Prostarix tests have potential for refining prostate cancer screening in conjunction with traditional prostate-specific antigen testing. The Confirm MDx and PCA3 tests have shown promise in identifying men who need be rebiopsied after a primary negative biopsy. Oncotype DX, Prolaris, the biopsy-based Decipher prostate cancer test, and ProMark may improve predictive risk stratification in addition to the traditional Gleason score and tumor stage. Decipher and Prolaris may predict biochemical recurrence and metastasis after radical prostatectomy and possibly help identify patients who need adjuvant therapy. Androgen receptor splice variant 7 appears effective in guiding the selection of second hormonal manipulation with abiraterone or enzalutamide versus chemotherapy when treating metastatic castration-resistant prostate cancer. PMID:27915475

  7. The epigenetic promise for prostate cancer diagnosis.

    PubMed

    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.

  8. Inflammation on Prostate Needle Biopsy is Associated with Lower Prostate Cancer Risk: A Meta-Analysis.

    PubMed

    Vasavada, Shaleen R; Dobbs, Ryan W; Kajdacsy-Balla, André A; Abern, Michael R; Moreira, Daniel M

    2018-05-01

    We performed a comprehensive literature review and meta-analysis to evaluate the association of inflammation on prostate needle biopsies and prostate cancer risk. We searched Embase®, PubMed® and Web of Science™ from January 1, 1990 to October 1, 2016 for abstracts containing the key words prostate cancer, inflammation and biopsy. Study inclusion criteria were original research, adult human subjects, cohort or case-control study design, histological inflammation on prostate needle biopsy and prostate cancer on histology. Two independent teams reviewed abstracts and extracted data from the selected manuscripts. Combined ORs and 95% CIs of any, acute and chronic inflammation were calculated using the random effects method. Of the 1,030 retrieved abstracts 46 underwent full text review and 25 were included in the final analysis, comprising a total of 20,585 subjects and 6,641 patients with prostate cancer. There was significant heterogeneity among studies (I 2 = 84.4%, p <0.001). The presence of any inflammation was significantly associated with a lower prostate cancer risk in 25 studies (OR 0.455, 95% CI 0.337-0.573). There was no evidence of publication bias (p >0.05). When subanalyzed by inflammation type, acute inflammation in 4 studies and chronic inflammation in 15 were each associated with a lower prostate cancer risk (OR 0.681, 95% CI 0.450-0.913 and OR 0.499, 95% CI 0.334-0.665, respectively). In a meta-analysis of 25 studies inflammation on prostate needle biopsy was associated with a lower prostate cancer risk. Clinically the presence of inflammation on prostate needle biopsy may lower the risk of a subsequent prostate cancer diagnosis. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2017-09-01

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

  10. Update on cryotherapy for localized prostate cancer.

    PubMed

    Ritch, Chad R; Katz, Aaron E

    2009-05-01

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

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

    PubMed Central

    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

  12. In situ vaccination with CD204 gene-silenced dendritic cell, not unmodified dendritic cell, enhances radiation therapy of prostate cancer

    PubMed Central

    Guo, Chunqing; Yi, Huanfa; Yu, Xiaofei; Zuo, Daming; Qian, Jie; Yang, Gary; Foster, Barbara A.; Subjeck, John R.; Sun, Xiaolei; Mikkelsen, Ross B.; Fisher, Paul B.; Wang, Xiang-Yang

    2012-01-01

    Given the complexity of prostate cancer progression and metastasis, multimodalities that target different aspects of tumor biology, e.g., radiotherapy (RT) in conjunction with immunotherapy, may provide the best opportunities for promoting clinical benefits in patients with high risk localized prostate cancer. Here we show that intratumoral administration of unmodified dendritic cells (DCs) failed to synergize with fractionated RT. However, ionizing radiation combined with in situ vaccination with DCs, in which the immunosuppressive scavenger receptor A (SRA/CD204) has been downregulated by lentivirus-mediated gene silencing, profoundly suppressed the growth of two mouse prostate cancers (e.g., RM1 and TRAMP-C2), and prolonged the lifespan of tumor-bearing animals. Treatment of subcutaneous tumors with this novel combinatorial radio-immunotherapeutic regimen resulted in a significant reduction in distant experimental metastases. SRA/CD204-silenced DCs were highly efficient in generating antigen or tumor-specific T cells with increased effector functions (e.g., cytokine production and tumoricidal activity). SRA/CD204 silencing-enhanced tumor cell death was associated with elevated IFN-γ levels in tumor tissue and increased tumor-infiltrating CD8+ cells. IFN-γ neutralization or depletion of CD8+ cells abrogated the SRA/CD204 downregulation-promoted antitumor efficacy, indicating a critical role of IFN-γ-producing CD8+ T cells. Therefore, blocking SRA/CD204 activity significantly enhances the therapeutic potency of local RT combined with in situ DC vaccination by promoting a robust systemic antitumor immunity. Further studies are warranted to test this novel combinatorial approach for translating into improved clinical outcomes in prostate cancer patients. PMID:22896667

  13. AR Alternative Splicing and Prostate Cancer Progression

    DTIC Science & Technology

    2013-07-01

    Meeting, May 14, 2011. Washington, DC. Department of Defense Prostate Cancer Research Program Innovative Minds in Prostate Cancer Today ( IMPaCT ...Role: Project 1 Leader Status: PENDING Transformative Impact Award Plymate (PI) 09/01/2013-08/31/2016 Department of Defense Prostate Cancer...Res 2002;62:6606–14. 29. Belancio VP, Hedges DJ, Deininger P. Mammalian non-LTR retro- transposons : for better or worse, in sickness and in health

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

    PubMed

    Cheetham, Philippa J; Katz, Aaron E

    2011-10-01

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

  15. Molecular pathways and targets in prostate cancer

    PubMed Central

    Shtivelman, Emma; Beer, Tomasz M.; Evans, Christopher P.

    2014-01-01

    Prostate cancer co-opts a unique set of cellular pathways in its initiation and progression. The heterogeneity of prostate cancers is evident at earlier stages, and has led to rigorous efforts to stratify the localized prostate cancers, so that progression to advanced stages could be predicted based upon salient features of the early disease. The deregulated androgen receptor signaling is undeniably most important in the progression of the majority of prostate tumors. It is perhaps because of the primacy of the androgen receptor governed transcriptional program in prostate epithelium cells that once this program is corrupted, the consequences of the ensuing changes in activity are pleotropic and could contribute to malignancy in multiple ways. Following localized surgical and radiation therapies, 20-40% of patients will relapse and progress, and will be treated with androgen deprivation therapies. The successful development of the new agents that inhibit androgen signaling has changed the progression free survival in hormone resistant disease, but this has not changed the almost ubiquitous development of truly resistant phenotypes in advanced prostate cancer. This review summarizes the current understanding of the molecular pathways involved in localized and metastatic prostate cancer, with an emphasis on the clinical implications of the new knowledge. PMID:25277175

  16. Current decision-making in prostate cancer therapy.

    PubMed

    Cox, Jared; Amling, Christopher L

    2008-05-01

    Prostate cancer continues to be the most prevalent cancer among American men. Localized prostate cancer is commonly diagnosed because of improved screening practices nationwide. Several options exist for the treatment of localized prostate cancer, and this review discusses the decision-making process facing patients diagnosed with this disease. No one treatment for localized prostate cancer has proven superior to date. For this reason patients have been found to use a number of resources to make an informed decision. These include physicians, spouses, family, friends, and different media. Urologists serve as the primary and most influential physicians and play an important role in the decision-making process. Patients, however, are assuming a more active role in this process as time evolves, especially with ease of access to multiple information resources. In deciding on a treatment for localized prostate cancer, patients must weigh the risks and benefits of each option. Urologists must provide patients with up-to-date information on these options and be aware of the different influences that surround these men during the decision-making process.

  17. Organoid culture systems for prostate epithelial tissue and prostate cancer tissue

    PubMed Central

    Drost, Jarno; Karthaus, Wouter R.; Gao, Dong; Driehuis, Else; Sawyers, Charles L.; Chen, Yu; Clevers, Hans

    2016-01-01

    Summary This protocol describes a recently developed strategy to generate 3D prostate organoid cultures from healthy mouse and human prostate (either bulk or FAC-sorted single luminal and basal cells), metastatic prostate cancer lesions and circulating tumour cells. Organoids derived from healthy material contain the differentiated luminal and basal cell types, whereas organoids derived from prostate cancer tissue mimic the histology of the tumour. The stepwise establishment of these cultures and the fully defined serum-free conditioned medium that is required to sustain organoid growth are outlined. Organoids established using this protocol can be used to study many different aspects of prostate biology, including homeostasis, tumorigenesis and drug discovery. PMID:26797458

  18. Prostate Cancer Prevention (PDQ®)—Patient Version

    Cancer.gov

    Prostate cancer prevention approaches include avoiding risk factors when possible, increasing protective factors, and chemoprevention. Learn more about prostate cancer prevention in this expert-reviewed summary.

  19. The integrated proactive surveillance system for prostate cancer.

    PubMed

    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

  20. XMRV Discovery and Prostate Cancer-Related Research.

    PubMed

    Kang, David E; Lee, Michael C; Das Gupta, Jaydip; Klein, Eric A; Silverman, Robert H

    2011-01-01

    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.

  1. Combination Therapy Improves Survival in Prostate Cancer Model | Center for Cancer Research

    Cancer.gov

    Surgery and radiotherapy are the recommended treatments for localized prostate cancer. Recurrent prostate cancer, however, is often treated with androgen-deprivation therapy. Most patients who undergo this type of therapy eventually develop castration-resistant prostate cancer (CRPC). Though initially androgen-related therapies for CRPC had been thought to be ineffective,

  2. Evaluation of prostate cancer antigen 3 for detecting prostate cancer: a systematic review and meta-analysis

    NASA Astrophysics Data System (ADS)

    Cui, Yong; Cao, Wenzhou; Li, Quan; Shen, Hua; Liu, Chao; Deng, Junpeng; Xu, Jiangfeng; Shao, Qiang

    2016-05-01

    Previous studies indicate that prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors. However, its clinical value has not been characterized. The aim of this study was to investigate the clinical value of the urine PCA3 test in the diagnosis of prostate cancer by pooling the published data. Clinical trials utilizing the urine PCA3 test for diagnosing prostate cancer were retrieved from PubMed and Embase. A total of 46 clinical trials including 12,295 subjects were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.65 (95% confidence interval [CI]: 0.63-0.66), 0.73 (95% CI: 0.72-0.74), 2.23 (95% CI: 1.91-2.62), 0.48 (95% CI: 0.44-0.52), 5.31 (95% CI: 4.19-6.73) and 0.75 (95% CI: 0.74-0.77), respectively. In conclusion, the urine PCA3 test has acceptable sensitivity and specificity for the diagnosis of prostate cancer and can be used as a non-invasive method for that purpose.

  3. Endocrine disruptors and prostate cancer risk

    PubMed Central

    Prins, Gail S

    2010-01-01

    There is increasing evidence both from epidemiology studies and animal models that specific endocrine-disrupting compounds may influence the development or progression of prostate cancer. In large part, these effects appear to be linked to interference with estrogen signaling, either through interacting with ERs or by influencing steroid metabolism and altering estrogen levels within the body. In humans, epidemiologic evidence links specific pesticides, PCBs and inorganic arsenic exposures to elevated prostate cancer risk. Studies in animal models also show augmentation of prostate carcinogenesis with several other environmental estrogenic compounds including cadmium, UV filters and BPA. Importantly, there appears to be heightened sensitivity of the prostate to these endocrine disruptors during the critical developmental windows including in utero and neonatal time points as well as during puberty. Thus infants and children may be considered a highly susceptible population for ED exposures and increased risk of prostate cancers with aging. PMID:18524946

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

    PubMed

    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.

  5. DNA mismatch repair gene MLH1 induces apoptosis in prostate cancer cells.

    PubMed

    Fukuhara, Shinichiro; Chang, Inik; Mitsui, Yozo; Chiyomaru, Takeshi; Yamamura, Soichiro; Majid, Shahana; Saini, Sharanjot; Hirata, Hiroshi; Deng, Guoren; Gill, Ankurpreet; Wong, Darryn K; Shiina, Hiroaki; Nonomura, Norio; Dahiya, Rajvir; Tanaka, Yuichiro

    2014-11-30

    Mismatch repair (MMR) enzymes have been shown to be deficient in prostate cancer (PCa). MMR can influence the regulation of tumor development in various cancers but their role on PCa has not been investigated. The aim of the present study was to determine the functional effects of the mutL-homolog 1 (MLH1) gene on growth of PCa cells. The DU145 cell line has been established as MLH1-deficient and thus, this cell line was utilized to determine effects of MLH1 by gene expression. Lack of MLH1 protein expression was confirmed by Western blotting in DU145 cells whereas levels were high in normal PWR-1E and RWPE-1 prostatic cells. MLH1-expressing stable transfectant DU145 cells were then created to characterize the effects this MMR gene has on various growth properties. Expression of MLH1 resulted in decreased cell proliferation, migration and invasion properties. Lack of cell growth in vivo also indicated a tumor suppressive effect by MLH1. Interestingly, MLH1 caused an increase in apoptosis along with phosphorylated c-Abl, and treatment with MLH1 siRNAs countered this effect. Furthermore, inhibition of c-Abl with STI571 also abrogated the effect on apoptosis caused by MLH1. These results demonstrate MLH1 protects against PCa development by inducing c-Abl-mediated apoptosis.

  6. DNA mismatch repair gene MLH1 induces apoptosis in prostate cancer cells

    PubMed Central

    Mitsui, Yozo; Chiyomaru, Takeshi; Yamamura, Soichiro; Majid, Shahana; Saini, Sharanjot; Hirata, Hiroshi; Deng, Guoren; Gill, Ankurpreet; Wong, Darryn K.; Shiina, Hiroaki; Nonomura, Norio; Dahiya, Rajvir; Tanaka, Yuichiro

    2014-01-01

    Mismatch repair (MMR) enzymes have been shown to be deficient in prostate cancer (PCa). MMR can influence the regulation of tumor development in various cancers but their role on PCa has not been investigated. The aim of the present study was to determine the functional effects of the mutL-homolog 1 (MLH1) gene on growth of PCa cells. The DU145 cell line has been established as MLH1-deficient and thus, this cell line was utilized to determine effects of MLH1 by gene expression. Lack of MLH1 protein expression was confirmed by Western blotting in DU145 cells whereas levels were high in normal PWR-1E and RWPE-1 prostatic cells. MLH1-expressing stable transfectant DU145 cells were then created to characterize the effects this MMR gene has on various growth properties. Expression of MLH1 resulted in decreased cell proliferation, migration and invasion properties. Lack of cell growth in vivo also indicated a tumor suppressive effect by MLH1. Interestingly, MLH1 caused an increase in apoptosis along with phosphorylated c-Abl, and treatment with MLH1 siRNAs countered this effect. Furthermore, inhibition of c-Abl with STI571 also abrogated the effect on apoptosis caused by MLH1. These results demonstrate MLH1 protects against PCa development by inducing c-Abl-mediated apoptosis. PMID:25526032

  7. Radiosensitization in prostate cancer: mechanisms and targets

    PubMed Central

    2013-01-01

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

  8. Chronic inflammation in benign prostate tissue is associated with high-grade prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial*

    PubMed Central

    Gurel, Bora; Lucia, M. Scott; Thompson, Ian M.; Goodman, Phyllis J.; Tangen, Catherine M.; Kristal, Alan R.; Parnes, Howard L.; Hoque, Ashraful; Lippman, Scott M.; Sutcliffe, Siobhan; Peskoe, Sarah B.; Drake, Charles G.; Nelson, William G.; De Marzo, Angelo M.; Platz, Elizabeth A.

    2014-01-01

    Background Chronic inflammation is hypothesized to influence prostate cancer development, although a definitive link has not been established. Methods Prostate cancer cases (N=191) detected on a for-cause (clinically indicated) or end-of-study (protocol directed) biopsy, and frequency-matched controls (N=209), defined as negative for cancer on an end-of-study biopsy, were sampled from the placebo arm of the Prostate Cancer Prevention Trial. Inflammation prevalence and extent in benign areas of biopsy cores were visually assessed using digital images of H&E stained sections. Logistic regression was used to estimate associations. Results 86.2% of cases and 78.2% of controls had at least one biopsy core (of 3 assessed) with inflammation in benign areas, most of which was chronic. Men who had at least one biopsy core with inflammation had 1.78 (95% CI 1.04–3.06) times the odds of prostate cancer compared with men who had zero cores with inflammation. The association was stronger for high-grade disease (Gleason sum 7–10, N=94; odds ratio [OR]=2.24, 95% CI 1.06–4.71). These patterns were present when restricting to cases and controls in whom intraprostatic inflammation was the least likely to have influenced biopsy recommendation because their PSA was low (<2 ng/mL at biopsy). Conclusion Inflammation, most of which was chronic, was common in benign prostate tissue, and was positively associated with prostate cancer, especially high-grade. The association did not appear to be due to detection bias. Impact This study supports an etiologic link between inflammation and prostate carcinogenesis, and suggests an avenue for prevention by mitigating intraprostatic inflammation. PMID:24748218

  9. Expression differences of circulating microRNAs in metastatic castration resistant prostate cancer and low-risk, localized prostate cancer.

    PubMed

    Nguyen, Han Christine Ngoc; Xie, Wanling; Yang, Ming; Hsieh, Chen-Lin; Drouin, Sarah; Lee, Gwo-Shu Mary; Kantoff, Philip W

    2013-03-01

    Recent studies show that microRNAs (miRNAs), small non-coding RNAs that negatively regulate gene expression, may have potential for monitoring cancer status. We investigated circulating miRNAs in prostate cancer that may be associated with the progression of hormone-sensitive primary tumors to metastatic castration resistant prostate cancer (CRPC) after androgen deprivation therapy. Using genome-wide expression profiling by TaqMan Human MicroRNA Arrays (Applied Biosystems) and/or quantitative real-time polymerase chain reaction, we compared the expression levels of miRNAs in serum samples from 28 patients of low-risk localized disease, 30 of high-risk localized disease and 26 of metastatic CRPC. We demonstrated that serum samples from patients of low risk, localized prostate cancer and metastatic CRPC patients exhibit distinct circulating miRNA signatures. MiR-375, miR-378*, and miR-141 were significantly over-expressed in serum from CRPC patients compared with serum from low-risk localized patients, while miR-409-3p was significantly under-expressed. In prostate primary tumor samples, miR-375 and miR-141 also had significantly higher expression levels compared with those in normal prostate tissue. Circulating miRNAs, particularly miR-375, miR-141, miR-378*, and miR-409-3p, are differentially expressed in serum samples from prostate cancer patients. In the search for improved minimally invasive methods to follow cancer pathogenesis, the correlation of disease status with the expression patterns of circulating miRNAs may indicate the potential importance of circulating miRNAs as prognostic markers for prostate cancer progression. Copyright © 2012 Wiley Periodicals, Inc.

  10. Prostate cancer link to vasectomy is weak.

    PubMed

    1998-03-01

    Health care providers and men seeking vasectomies are still unsure about the nature of the association between vasectomy and prostate cancer. Two large cohort studies published in 1993 found increased relative risks for prostate cancer in vasectomized men of 1.56 and 1.66. However, this level of increased relative risk represents only a weak association between the procedure and cancer. Three other studies of similar design reported no such association. Several divisions of the National Institutes of Health examined the research and issued the joint statement in 1993 that providers should continue to offer vasectomy and perform the procedure, the reversal of vasectomies is unwarranted to prevent prostate cancer, and screening for prostate cancer should not be any different for men who have had a vasectomy than for those who have not. Joel Feigin, MD, associate professor of family medicine at Robert Wood Johnson Medical School in New Brunswick, NJ, and director of the Coventry No-Scalpel Vasectomy Center in Phillipsburg, NJ, recommends dealing proactively with the cancer link as a standard part of counseling. Thomas R. Pritchett, MD, a urologist on the clinical faculty of the University of Washington and the department of urology at Virginia Mason Medical Center in Seattle says that the strongest link to increased risk for prostate cancer is family history. Diet, race, and vasectomy are only weak associations. A definite link also exists between testosterone and prostate cancer, but undergoing vasectomy neither increases nor decreases a man's testosterone level.

  11. Department of Defense prostate cancer clinical trials consortium: a new instrument for prostate cancer clinical research.

    PubMed

    Morris, Michael J; Basch, Ethan M; Wilding, George; Hussain, Maha; Carducci, Michael A; Higano, Celestia; Kantoff, Philip; Oh, William K; Small, Eric J; George, Daniel; Mathew, Paul; Beer, Tomasz M; Slovin, Susan F; Ryan, Charles; Logothetis, Christopher; Scher, Howard I

    2009-01-01

    In 2005, the US Department of Defense, through the US Army Medical Research and Materiel Command, Office of the Congressionally Directed Medical Research Programs, created a funding mechanism to form a clinical trials consortium to conduct phase I and II studies in prostate cancer. This is the first report of the Prostate Cancer Clinical Trials Consortium (PCCTC). The Department of Defense award supports a consortium of 10 prostate cancer research centers. Memorial Sloan-Kettering Cancer Center was awarded the Coordinating Center grant for the consortium and charged with creating an infrastructure to conduct early-phase multicenter clinical trials. Each participating center was required to introduce >or=1 clinical trial per year and maintain accrual of a minimum of 35 patients per year. The PCCTC was launched in 2006 and now encompasses 10 leading prostate cancer research centers. Fifty-one trials have been opened, and 1386 patients have been accrued at member sites. Members share an online clinical trial management system for protocol tracking, electronic data capture, and data storage. A legal framework has been instituted, and standard operating procedures, an administrative structure, editorial support, centralized budgeting, and mechanisms for scientific review are established. The PCCTC fulfills a congressional directive to create a clinical trials instrument dedicated to early-phase prostate cancer studies. The member institutions have built an administrative, informatics, legal, financial, statistical, and scientific infrastructure to support this endeavor. Clinical trials are open and accruing in excess of federally mandated goals.

  12. Therapeutic targeting of SPINK1-positive prostate cancer.

    PubMed

    Ateeq, Bushra; Tomlins, Scott A; Laxman, Bharathi; Asangani, Irfan A; Cao, Qi; Cao, Xuhong; Li, Yong; Wang, Xiaoju; Feng, Felix Y; Pienta, Kenneth J; Varambally, Sooryanarayana; Chinnaiyan, Arul M

    2011-03-02

    Gene fusions involving ETS (erythroblastosis virus E26 transformation-specific) family transcription factors are found in ~50% of prostate cancers and as such can be used as a basis for the molecular subclassification of prostate cancer. Previously, we showed that marked overexpression of SPINK1 (serine peptidase inhibitor, Kazal type 1), which encodes a secreted serine protease inhibitor, defines an aggressive molecular subtype of ETS fusion-negative prostate cancers (SPINK1+/ETS⁻, ~10% of all prostate cancers). Here, we examined the potential of SPINK1 as an extracellular therapeutic target in prostate cancer. Recombinant SPINK1 protein (rSPINK1) stimulated cell proliferation in benign RWPE as well as cancerous prostate cells. Indeed, RWPE cells treated with either rSPINK1 or conditioned medium from 22RV1 prostate cancer cells (SPINK1+/ETS⁻) significantly increased cell invasion and intravasation when compared with untreated cells. In contrast, knockdown of SPINK1 in 22RV1 cells inhibited cell proliferation, cell invasion, and tumor growth in xenograft assays. 22RV1 cell proliferation, invasion, and intravasation were attenuated by a monoclonal antibody (mAb) to SPINK1 as well. We also demonstrated that SPINK1 partially mediated its neoplastic effects through interaction with the epidermal growth factor receptor (EGFR). Administration of antibodies to SPINK1 or EGFR (cetuximab) in mice bearing 22RV1 xenografts attenuated tumor growth by more than 60 and 40%, respectively, or ~75% when combined, without affecting PC3 xenograft (SPINK1⁻/ETS⁻) growth. Thus, this study suggests that SPINK1 may be a therapeutic target in a subset of patients with SPINK1+/ETS⁻ prostate cancer. Our results provide a rationale for both the development of humanized mAbs to SPINK1 and evaluation of EGFR inhibition in SPINK1+/ETS⁻ prostate cancers.

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

    PubMed

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

    2013-01-15

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

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

    PubMed

    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.

  15. Diagnosis of prostate cancer via nanotechnological approach

    PubMed Central

    Kang, Benedict J; Jeun, Minhong; Jang, Gun Hyuk; Song, Sang Hoon; Jeong, In Gab; Kim, Choung-Soo; Searson, Peter C; Lee, Kwan Hyi

    2015-01-01

    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. PMID:26527873

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

    PubMed Central

    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

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

    PubMed

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

    2014-01-01

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

  18. Prostate Cancer Relevant Antigens and Enzymes for Targeted Drug Delivery

    PubMed Central

    Barve, Ashutosh; Jin, Wei; Cheng, Kun

    2014-01-01

    Chemotherapy is one of the most widely used approaches in combating advanced prostate cancer, but its therapeutic efficacy is usually insufficient due to lack of specificity and associated toxicity. Lack of targeted delivery to prostate cancer cells is also the primary obstacles in achieving feasible therapeutic effect of other promising agents including peptide, protein, and nucleic acid. Consequently, there remains a critical need for strategies to increase the selectivity of anti-prostate cancer agents. This review will focus on various prostate cancer-specific antigens and enzymes that could be exploited for prostate cancer targeted drug delivery. Among various targeting strategies, active targeting is the most advanced approach to specifically deliver drugs to their designated cancer cells. In this approach, drug carriers are modified with targeting ligands that can specifically bind to prostate cancer-specific antigens. Moreover, there are several specific enzymes in the tumor microenvironment of prostate cancer that can be exploited for stimulus-responsive drug delivery systems. These systems can specifically release the active drug in the tumor microenvironment of prostate cancer, leading to enhanced tumor penetration efficiency. PMID:24878184

  19. Association of androgen metabolism gene polymorphisms with prostate cancer risk and androgen concentrations: Results from the Prostate Cancer Prevention Trial.

    PubMed

    Price, Douglas K; Chau, Cindy H; Till, Cathee; Goodman, Phyllis J; Leach, Robin J; Johnson-Pais, Teresa L; Hsing, Ann W; Hoque, Ashraful; Parnes, Howard L; Schenk, Jeannette M; Tangen, Catherine M; Thompson, Ian M; Reichardt, Juergen K V; Figg, William D

    2016-08-01

    Prostate cancer is highly influenced by androgens and genes. The authors investigated whether genetic polymorphisms along the androgen biosynthesis and metabolism pathways are associated with androgen concentrations or with the risk of prostate cancer or high-grade disease from finasteride treatment. A nested case-control study from the Prostate Cancer Prevention Trial using data from men who had biopsy-proven prostate cancer (cases) and a group of biopsy-negative, frequency-matched controls was conducted to investigate the association of 51 single nucleotide polymorphisms (SNPs) in 12 genes of the androgen pathway with overall (total), low-grade, and high-grade prostate cancer incidence and serum hormone concentrations. There were significant associations of genetic polymorphisms in steroid 5α-reductase 1 (SRD5A1) (reference SNPs: rs3736316, rs3822430, rs1560149, rs248797, and rs472402) and SRD5A2 (rs2300700) with the risk of high-grade prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial; 2 SNPs were significantly associated with an increased risk (SRD5A1 rs472402 [odds ratio, 1.70; 95% confidence interval, 1.05-2.75; Ptrend = .03] and SRD5A2 rs2300700 [odds ratio, 1.94; 95% confidence interval, 1.19-3.18; Ptrend = .01]). Eleven SNPs in SRD5A1, SRD5A2, cytochrome P450 family 1, subfamily B, polypeptide 1 (CYP1B1), and CYP3A4 were associated with modifying the mean concentrations of serum androgen and sex hormone-binding globulin; and 2 SNPs (SRD5A1 rs824811 and CYP1B1 rs10012; Ptrend < .05) consistently and significantly altered all androgen concentrations. Several SNPs (SRD5A1 rs3822430, SRD5A2 rs2300700, CYP3A43 rs800672, and CYP19 rs700519; Ptrend < .05) were significantly associated with both circulating hormone levels and prostate cancer risk. Germline genetic variations of androgen-related pathway genes are associated with serum androgen concentrations and the risk of prostate cancer. Further studies to examine the functional

  20. Incidental Prostate Cancer in Transurethral Resection of the Prostate Specimens in the Modern Era

    PubMed Central

    Barbieri, Christopher; Te, Alexis E.; Kaplan, Steven A.

    2014-01-01

    Objectives. To identify rates of incidentally detected prostate cancer in patients undergoing surgical management of benign prostatic hyperplasia (BPH). Materials and Methods. A retrospective review was performed on all transurethral resections of the prostate (TURP) regardless of technique from 2006 to 2011 at a single tertiary care institution. 793 men (ages 45–90) were identified by pathology specimen. Those with a known diagnosis of prostate cancer prior to TURP were excluded (n = 22) from the analysis. Results. 760 patients had benign pathology; eleven (1.4%) patients were found to have prostate cancer. Grade of disease ranged from Gleason 3 + 3 = 6 to Gleason 3 + 4 = 7. Nine patients had cT1a disease and two had cT1b disease. Seven patients were managed by active surveillance with no further events, one patient underwent radiation, and three patients underwent radical prostatectomy. Conclusions. Our series demonstrates that 1.4% of patients were found to have prostate cancer, of these 0.5% required treatment. Given the low incidental prostate cancer detection rate, the value of pathologic review of TURP specimens may be limited depending on the patient population. PMID:24876835

  1. Incidental prostate cancer in transurethral resection of the prostate specimens in the modern era.

    PubMed

    Otto, Brandon; Barbieri, Christopher; Lee, Richard; Te, Alexis E; Kaplan, Steven A; Robinson, Brian; Chughtai, Bilal

    2014-01-01

    Objectives. To identify rates of incidentally detected prostate cancer in patients undergoing surgical management of benign prostatic hyperplasia (BPH). Materials and Methods. A retrospective review was performed on all transurethral resections of the prostate (TURP) regardless of technique from 2006 to 2011 at a single tertiary care institution. 793 men (ages 45-90) were identified by pathology specimen. Those with a known diagnosis of prostate cancer prior to TURP were excluded (n = 22) from the analysis. Results. 760 patients had benign pathology; eleven (1.4%) patients were found to have prostate cancer. Grade of disease ranged from Gleason 3 + 3 = 6 to Gleason 3 + 4 = 7. Nine patients had cT1a disease and two had cT1b disease. Seven patients were managed by active surveillance with no further events, one patient underwent radiation, and three patients underwent radical prostatectomy. Conclusions. Our series demonstrates that 1.4% of patients were found to have prostate cancer, of these 0.5% required treatment. Given the low incidental prostate cancer detection rate, the value of pathologic review of TURP specimens may be limited depending on the patient population.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

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

    2016-11-23

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

  5. African Americans' Perceptions of Prostate-Specific Antigen Prostate Cancer Screening

    ERIC Educational Resources Information Center

    Hunter, Jaimie C.; Vines, Anissa I.; Carlisle, Veronica

    2015-01-01

    Background: In 2012, the U.S. Preventive Services Task Force released a hotly debated recommendation against prostate-specific antigen testing for all men. The present research examines African Americans' beliefs about their susceptibility to prostate cancer (PCa) and the effectiveness of prostate-specific antigen testing in the context of the…

  6. Are strict vegetarians protected against prostate cancer?1

    PubMed Central

    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

  7. Decision Aids in Improving Knowledge in Patients With Newly Diagnosed Prostate Cancer

    ClinicalTrials.gov

    2018-06-08

    Stage II Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage I Prostate Cancer; PSA Level Five to Ten; PSA Level Less Than Five; PSA Level Ten to Fifty

  8. DESNT: A Poor Prognosis Category of Human Prostate Cancer.

    PubMed

    Luca, Bogdan-Alexandru; Brewer, Daniel S; Edwards, Dylan R; Edwards, Sandra; Whitaker, Hayley C; Merson, Sue; Dennis, Nening; Cooper, Rosalin A; Hazell, Steven; Warren, Anne Y; Eeles, Rosalind; Lynch, Andy G; Ross-Adams, Helen; Lamb, Alastair D; Neal, David E; Sethia, Krishna; Mills, Robert D; Ball, Richard Y; Curley, Helen; Clark, Jeremy; Moulton, Vincent; Cooper, Colin S

    2017-03-06

    A critical problem in the clinical management of prostate cancer is that it is highly heterogeneous. Accurate prediction of individual cancer behaviour is therefore not achievable at the time of diagnosis leading to substantial overtreatment. It remains an enigma that, in contrast to breast cancer, unsupervised analyses of global expression profiles have not currently defined robust categories of prostate cancer with distinct clinical outcomes. To devise a novel classification framework for human prostate cancer based on unsupervised mathematical approaches. Our analyses are based on the hypothesis that previous attempts to classify prostate cancer have been unsuccessful because individual samples of prostate cancer frequently have heterogeneous compositions. To address this issue, we applied an unsupervised Bayesian procedure called Latent Process Decomposition to four independent prostate cancer transcriptome datasets obtained using samples from prostatectomy patients and containing between 78 and 182 participants. Biochemical failure was assessed using log-rank analysis and Cox regression analysis. Application of Latent Process Decomposition identified a common process in all four independent datasets examined. Cancers assigned to this process (designated DESNT cancers) are characterized by low expression of a core set of 45 genes, many encoding proteins involved in the cytoskeleton machinery, ion transport, and cell adhesion. For the three datasets with linked prostate-specific antigen failure data following prostatectomy, patients with DESNT cancer exhibited poor outcome relative to other patients (p=2.65×10 -5 , p=4.28×10 -5 , and p=2.98×10 -8 ). When these three datasets were combined the independent predictive value of DESNT membership was p=1.61×10 -7 compared with p=1.00×10 -5 for Gleason sum. A limitation of the study is that only prediction of prostate-specific antigen failure was examined. Our results demonstrate the existence of a novel poor

  9. Influence of the neural microenvironment on prostate cancer

    PubMed Central

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

    2017-01-01

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

  10. Enrichment of prostate cancer stem cells from primary prostate cancer cultures of biopsy samples

    PubMed Central

    Wang, Shunqi; Huang, Shengsong; Zhao, Xin; Zhang, Qimin; Wu, Min; Sun, Feng; Han, Gang; Wu, Denglong

    2014-01-01

    This study was to enrich prostate cancer stem cells (PrCSC) from primary prostate cancer cultures (PPrCC). Primary prostate cancer cells were amplified in keratinocyte serum-free medium with epidermal growth factor (EGF) and bovine pituitary extract (BPE), supplemented with leukemia inhibitory factor (LIF), stem cell factor (SCF) and cholera toxin. After amplification, cells were transferred into ultra-low attachment dishes with serum-free DMEM/F12 medium, supplemented with EGF, basic fibroblast growth factor (bFGF), bovine serum albumin (BSA), insulin, and N2 nutrition. Expression of cell-type-specific markers was determined by RT-qPCR and immunostaining. Tumorigenicity of enriched PrCSC was determined by soft agar assay and xenograft assay in NOD/SCID mice. Biopsy samples from 19 confirmed prostate cancer patients were used for establishing PPrCC, and 18 cases (95%) succeeded. Both basal marker (CK5) and luminal markers (androgen receptor and CK8) strongly co-expressed in most of PPrCC, indicating their basal epithelial origin. After amplification under adherent culture condition in vitro, transient amplifying cells were the dominant cells. Sphere formation efficiency (SFE) of passaged PPrCC was about 0.5%, which was 27 times lower than SFE of LNCaP (13.67%) in the same condition. Compared with adherent cells from PPrCC, prostasphere from PPrCC showed up regulated stem cell markers and increased tumorigenic potential in soft-agar assay. However, spheroid cells from PPrCC prostasphere failed to initiate tumor in xenograft assay in 6 months. Thus, PPrCC can be established and amplified from prostate cancer biopsy samples. Our modified sphere culture system can enrich PrCSC from PPrCC. PMID:24427338

  11. Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue

    DTIC Science & Technology

    2016-12-01

    Award Number: W81XWH-11-1-0744 TITLE: Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated...Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non- Neoplastic Prostate Tissue 5b. GRANT NUMBER 10623678 5c...Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The goal of this project was to develop molecular models to

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

    DTIC Science & Technology

    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

  13. Studying circulating prostate cancer cells by in-vivo flow cytometer

    NASA Astrophysics Data System (ADS)

    Guo, Jin; Gu, Zhengqin; Chen, Tong; Wang, Cheng; Wei, Xunbin

    2012-03-01

    Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal near-infrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. We have measured the depletion kinetics of cancer cells with different metastatic potential. Interestingly, more invasive PC-3 prostate cancer cells are depleted faster from the circulation than LNCaP cells.

  14. Chemotherapy of prostate cancer: present and future.

    PubMed

    Trump, Donald; Lau, Yiu-Keung

    2003-06-01

    The role of chemotherapy in prostate cancer continues to evolve. In men with symptomatic androgen-independent prostate cancer, significant reduction in pain and analgesic requirements are achievable with mitoxantrone and glucocorticoid combinations compared with glucocorticoids alone. However, survival rates are not improved. Taxane-based combinations with estramustine phosphate or other new agents show promise. Prostate-specific antigen response rates with these combinations appear to be 1.5 to 2 times more frequent than with mitoxantrone-based combinations. Randomized trials of taxane versus mitoxantrone-based therapies are underway. New agents and applications of current agents in adjuvant settings should be explored if survival in men with prostate cancer is to be improved.

  15. Prostate cancer antigen 3 gene expression in peripheral blood and urine sediments from prostate cancer and benign prostatic hyperplasia patients versus healthy individuals.

    PubMed

    Moradi Sardareh, Hemen; Goodarzi, Mohammad Taghi; Yadegar-Azari, Reza; Poorolajal, Jalal; Mousavi-Bahar, Seyed Habibollah; Saidijam, Massoud

    2014-11-30

    To determine the expression of prostate cancer antigen 3 (PCA3) gene in peripheral blood and urine sediments from patients with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and normal subjects. A total number of 48 patients [24 with biopsy proven prostate cancer (PCa) and 24 with benign prostate hyperplasia (BPH)] were studied. Twenty-four healthy individuals were also recruited as control group. After blood and urine sampling, total RNA was extracted and cDNA was synthesized. Expression of PCA3 gene was assessed by quantitative reverse transcription polymerase chain reaction. Comparison of PCA3 gene expression between control and BPH groups indicated no statistically significant differences in both urine and blood samples. Patients with PCa demonstrated an increased PCA3 gene expression rate compared to control and BPH groups (10.64 and 7.17 folds, respectively). The rate of fold increased PCA3 gene expression in urine was 20.90, 20.90, and 20.35 in patients with PCa, BPH and normal subjects, respectively. Evaluation of PCA3 gene expression can be considered as a reliable marker for detection of PCa. Increased level of this marker in urine sediments is more sensitive than blood for distinguishing between cancerous and non-cancerous groups. 

  16. The Integrated Proactive Surveillance System for Prostate Cancer

    PubMed Central

    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

  17. Locus-specific gene repositioning in prostate cancer

    PubMed Central

    Leshner, Marc; Devine, Michelle; Roloff, Gregory W.; True, Lawrence D.; Misteli, Tom; Meaburn, Karen J.

    2016-01-01

    Genes occupy preferred spatial positions within interphase cell nuclei. However, positioning patterns are not an innate feature of a locus, and genes can alter their localization in response to physiological and pathological changes. Here we screen the radial positioning patterns of 40 genes in normal, hyperplasic, and malignant human prostate tissues. We find that the overall spatial organization of the genome in prostate tissue is largely conserved among individuals. We identify three genes whose nuclear positions are robustly altered in neoplastic prostate tissues. FLI1 and MMP9 position differently in prostate cancer than in normal tissue and prostate hyperplasia, whereas MMP2 is repositioned in both prostate cancer and hyperplasia. Our data point to locus-specific reorganization of the genome during prostate disease. PMID:26564800

  18. A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

    PubMed Central

    Hellwinkel, Olaf J. C.; Sellier, Christina; Sylvester, Yu-Mi Jessica; Brase, Jan C.; Isbarn, Hendrik; Erbersdobler, Andreas; Steuber, Thomas; Sültmann, Holger; Schlomm, Thorsten; Wagner, Christina

    2013-01-01

    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. PMID:23459235

  19. Magnetic resonance spectroscopy-guided transperineal prostate biopsy and brachytherapy for recurrent prostate cancer.

    PubMed

    Barnes, Agnieszka Szot; Haker, Steven J; Mulkern, Robert V; So, Minna; D'Amico, Anthony V; Tempany, Clare M

    2005-12-01

    Brachytherapy targeted to the peripheral zone with magnetic resonance imaging (MRI) guidance is a prostate cancer treatment option with potentially fewer complications than other treatments. Follow-up MRI when failure is suspected is, however, difficult because of radiation-induced changes. Furthermore, MR spectroscopy (MRS) is compromised by susceptibility artifacts from radioactive seeds in the peripheral zone. We report a case in which combined MRI/MRS was useful for the detection of prostate cancer in the transitional zone in patients previously treated with MR-guided brachytherapy. We propose that MRI/MRS can help detect recurrent prostate cancer, guide prostate biopsy, and help manage salvage treatment decisions.

  20. Targeting the Neural Microenvironment in Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    nerve-prostate cancer cell interactions. Subtask 1: Sub-aim 2.1. DRG PNI studies with DU145 prostate cancer cells (months 4-15) We have received...Subtask 2: Sub-aim 2.2. DRG PNI studies with other prostate cancer cell lines (months 12- 36) This will be carried beginning in Year 2 Subtask 3: Sub...targets of these pathways such as p70S6 kinase. We are well positioned to proceed with DRG and in vivo mouse studies as well as immunohistochemistry

  1. Targeting the Neural Microenvironment in Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    nerve-prostate cancer cell interactions. Subtask 1: Sub-aim 2.1. DRG PNI studies with DU145 prostate cancer cells (months 4-15) We have received...Subtask 2: Sub-aim 2.2. DRG PNI studies with other prostate cancer cell lines (months 12- 36) This will be carried beginning in Year 2 Subtask 3: Sub...potentiated by GFRA1. These studies suggest that GFRA1 may be partially limiting in our system . Moving forward we will need explore whether GFRA1

  2. Fatty acid binding protein 4 enhances prostate cancer progression by upregulating matrix metalloproteinases and stromal cell cytokine production

    PubMed Central

    Huang, Mingguo; Narita, Shintaro; Inoue, Takamitsu; Koizumi, Atsushi; Saito, Mitsuru; Tsuruta, Hiroshi; Numakura, Kazuyuki; Satoh, Shigeru; Nanjo, Hiroshi; Sasaki, Takehiko; Habuchi, Tomonori

    2017-01-01

    Fatty acid binding protein 4 (FABP4) is an abundant protein in adipocytes, and its production is influenced by high-fat diet (HFD) or obesity. The prostate stromal microenvironment induces proinflammatory cytokine production, which is key for the development and progression of prostate cancer (PCa). Here, we show that high FABP4 expression and its secretion by PCa cells directly stimulated PCa cell invasiveness by upregulating matrix metalloproteinases through phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling pathways. In addition, prostate stromal cells augmented PCa cell invasiveness by secreting interleukin-8 and -6 in response to FABP4. This was abrogated by the FABP4 specific inhibitor, BMS309403. Furthermore, a mouse xenograft experiment showed HFD enhanced PCa metastasis and invasiveness by the upregulation of FABP4 and interleukin-8. Clinically, the serum level of FABP4 was significantly associated with an aggressive type of PCa rather than obesity. Taken together, FABP4 may enhance PCa progression and invasiveness by upregulating matrix metalloproteinases and cytokine production in the PCa stromal microenvironment, especially under HFD or obesity. PMID:29340091

  3. Prostate atypia: does repeat biopsy detect clinically significant prostate cancer?

    PubMed

    Dorin, Ryan P; Wiener, Scott; Harris, Cory D; Wagner, Joseph R

    2015-05-01

    While the treatment pathway in response to benign or malignant prostate biopsies is well established, there is uncertainty regarding the risk of subsequently diagnosing prostate cancer when an initial diagnosis of prostate atypia is made. As such, we investigated the likelihood of a repeat biopsy diagnosing prostate cancer (PCa) in patients in which an initial biopsy diagnosed prostate atypia. We reviewed our prospectively maintained prostate biopsy database to identify patients who underwent a repeat prostate biopsy within one year of atypia (atypical small acinar proliferation; ASAP) diagnosis between November 1987 and March 2011. Patients with a history of PCa were excluded. Chart review identified patients who underwent radical prostatectomy (RP), radiotherapy (RT), or active surveillance (AS). For some analyses, patients were divided into two subgroups based on their date of service. Ten thousand seven hundred and twenty patients underwent 13,595 biopsies during November 1987-March 2011. Five hundred and sixty seven patients (5.3%) had ASAP on initial biopsy, and 287 (50.1%) of these patients underwent a repeat biopsy within one year. Of these, 122 (42.5%) were negative, 44 (15.3%) had atypia, 19 (6.6%) had prostatic intraepithelial neoplasia, and 102 (35.6%) contained PCa. Using modified Epstein's criteria, 27/53 (51%) patients with PCa on repeat biopsy were determined to have clinically significant tumors. 37 (36.3%) proceeded to RP, 25 (24.5%) underwent RT, and 40 (39.2%) received no immediate treatment. In patients who underwent surgery, Gleason grade on final pathology was upgraded in 11 (35.5%), and downgraded 1 (3.2%) patient. ASAP on initial biopsy was associated with a significant risk of PCa on repeat biopsy in patients who subsequently underwent definitive local therapy. Patients with ASAP should be counseled on the probability of harboring both clinically significant and insignificant prostate cancer. © 2015 Wiley Periodicals, Inc.

  4. Next generation patient-derived prostate cancer xenograft models

    PubMed Central

    Lin, Dong; Xue, Hui; Wang, Yuwei; Wu, Rebecca; Watahiki, Akira; Dong, Xin; Cheng, Hongwei; Wyatt, Alexander W; Collins, Colin C; Gout, Peter W; Wang, Yuzhuo

    2014-01-01

    There is a critical need for more effective therapeutic approaches for prostate cancer. Research in this area, however, has been seriously hampered by a lack of clinically relevant, experimental in vivo models of the disease. This review particularly focuses on the development of prostate cancer xenograft models based on subrenal capsule grafting of patients’ tumor tissue into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. This technique allows successful development of transplantable, patient-derived cancer tissue xenograft lines not only from aggressive metastatic, but also from localized prostate cancer tissues. The xenografts have been found to retain key biological properties of the original malignancies, including histopathological and molecular characteristics, tumor heterogeneity, response to androgen ablation and metastatic ability. As such, they are highly clinically relevant and provide valuable tools for studies of prostate cancer progression at cellular and molecular levels, drug screening for personalized cancer therapy and preclinical drug efficacy testing; especially when a panel of models is used to cover a broader spectrum of the disease. These xenograft models could therefore be viewed as next-generation models of prostate cancer. PMID:24589467

  5. RNA splicing and splicing regulator changes in prostate cancer pathology.

    PubMed

    Munkley, Jennifer; Livermore, Karen; Rajan, Prabhakar; Elliott, David J

    2017-09-01

    Changes in mRNA splice patterns have been associated with key pathological mechanisms in prostate cancer progression. The androgen receptor (abbreviated AR) transcription factor is a major driver of prostate cancer pathology and activated by androgen steroid hormones. Selection of alternative promoters by the activated AR can critically alter gene function by switching mRNA isoform production, including creating a pro-oncogenic isoform of the normally tumour suppressor gene TSC2. A number of androgen-regulated genes generate alternatively spliced mRNA isoforms, including a prostate-specific splice isoform of ST6GALNAC1 mRNA. ST6GALNAC1 encodes a sialyltransferase that catalyses the synthesis of the cancer-associated sTn antigen important for cell mobility. Genetic rearrangements occurring early in prostate cancer development place ERG oncogene expression under the control of the androgen-regulated TMPRSS2 promoter to hijack cell behaviour. This TMPRSS2-ERG fusion gene shows different patterns of alternative splicing in invasive versus localised prostate cancer. Alternative AR mRNA isoforms play a key role in the generation of prostate cancer drug resistance, by providing a mechanism through which prostate cancer cells can grow in limited serum androgen concentrations. A number of splicing regulator proteins change expression patterns in prostate cancer and may help drive key stages of disease progression. Up-regulation of SRRM4 establishes neuronal splicing patterns in neuroendocrine prostate cancer. The splicing regulators Sam68 and Tra2β increase expression in prostate cancer. The SR protein kinase SRPK1 that modulates the activity of SR proteins is up-regulated in prostate cancer and has already given encouraging results as a potential therapeutic target in mouse models.

  6. Is it necessary to cure prostate cancer when it is possible? (Understanding the role of prostate inflammation resolution to prostate cancer evolution)

    PubMed Central

    Wheeler, Ronald E

    2007-01-01

    Objective: Definitive therapy with radical prostatectomy, cryotherapy, or radiation therapy generally follows the initial diagnosis of prostate cancer, particularly when men have at least 10 additional years of life expectancy. There is growing concern regarding the optimal conservative treatment for patients who decline or do not otherwise qualify for such definitive curative treatment. For those patients who choose a watchful waiting approach, it would be beneficial to know what specific dietary and nutritional methods could potentially slow the progression of their disease. In this prospective study, it was our goal to analyze the efficacy and safety of treating prostate cancer conservatively using the principles of a Mediterranean diet in association with a specific prostate nutritional supplement. Method: Twenty-three men aged 43–74 (median age: 64) with biopsy proven, organ-confined prostate cancer who had already declined immediate hormonal therapy and attempts at a curative cancer treatment agreed to participate in a Chronic Disease Management (CDM) protocol highlighted by diet with a specific prostate nutritional supplement. The diet recommended was a modified Mediterranean diet while a patented nutritional prostatitis formula (Peenuts®) was the supplement common to all patients. Prostate specific antigen (PSA), a recognized marker of prostate disease and prostate cancer activity, was the primary indicator to validate exacerbation or suppression of disease. All men were followed with serial PSA testing, a digital rectal exam, an International Prostate Symptom Score index (IPSS-Index) and an expressed prostatic secretion (EPS) examination. The primary Gleason sum/score represented in this study was 6 (n = 11), while Gleason sum patterns 5, 5/6, 6/7, and 7 were also evaluated. Referencing the Partin Tables, organ confinement was predicted to be 66%. Results: Eighty-seven percent of men (n = 20) noted a 58% reduction (range of improvement: 13%–90%) in

  7. High-Intensity Focused Ultrasound in Treating Participants With Intermediate and High-risk Prostate Cancer

    ClinicalTrials.gov

    2018-06-13

    Stage I Prostate Cancer AJCC v8; Stage II Prostate Cancer AJCC v8; Stage IIA Prostate Cancer AJCC v8; Stage IIB Prostate Cancer AJCC v8; Stage IIC Prostate Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8

  8. Stages of Prostate Cancer

    MedlinePlus

    ... from making testosterone. However, estrogens are seldom used today in the treatment of prostate cancer because of ... or better than the standard treatment . Many of today's standard treatments for cancer are based on earlier ...

  9. Epigenetic susceptibility factors for prostate cancer with aging.

    PubMed

    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.

  10. Prostate Cancer Biospecimen Cohort Study

    DTIC Science & Technology

    2016-10-01

    goal of the study is development of a Prostate Cancer Biorepository Network (PCBN) resource site with high quality and well-annotated urine , blood...with no coordinating center and each site will be responsible for maintaining/storing their own data/ samples . 15. SUBJECT TERMS Prostate cancer...Biorepository Network (PCBN) resource site with high quality and well-annotated urine , blood, and tissue specimens as part of a multi-institutional Department of

  11. Immunotherapy for Prostate Cancer Enters Its Golden Age

    PubMed Central

    Boikos, Sosipatros A.; Antonarakis, Emmanuel S.

    2012-01-01

    In the United States, prostate cancer is the most frequent malignancy in men and ranks second in terms of mortality. Although recurrent or metastatic disease can be managed initially with androgen ablation, most patients eventually develop castration-resistant disease within a number of years, for which conventional treatments (eg, chemotherapy) provide only modest benefits. In the last few years, immunotherapy has emerged as an exciting therapeutic modality for advanced prostate cancer, and this field is evolving rapidly. Encouragingly, the US Food and Drug Administration (FDA) has recently approved two novel immunotherapy agents for patients with advanced cancer: the antigen presenting cell-based product sipuleucel-T and the anti-CTLA4 (cytotoxic T-lymphocyte antigen 4) antibody ipilimumab, based on improvements in overall survival in patients with castration-resistant prostate cancer and metastatic melanoma, respectively. Currently, a number of trials are investigating the role of various immunological approaches for the treatment of prostate cancer, many of them with early indications of success. As immunotherapy for prostate cancer enters its golden age, the challenge of the future will be to design rational combinations of immunotherapy agents with each other or with other standard prostate cancer treatments in an effort to improve patient outcomes further. PMID:22844202

  12. The influence of PSA-RNA yield on the analysis of expressed prostatic secretions (EPS) for prostate cancer diagnosis.

    PubMed

    Whelan, Christopher; Crocitto, Laura; Kawachi, Mark; Chan, Kevin; Smith, David; Wilson, Timothy; Smith, Steven

    2013-02-01

    In patients with prostate cancer, luminal prostate-specific antigen (PSA) enters the circulation because the basement membrane and glandular epithelium are damaged. Given that excess mobilization of prostate cells during prostatic massage can influence normalization in diagnostic testing, we studied PSA mRNA levels in expressed prostatic secretions (EPS) from patients undergoing biopsy for prostate cancer to determine if prostate cells are preferentially mobilized from patients with prostate cancer during prostatic massage. Quantitative Reverse-Transcription PCR (qRT-PCR) was used to measure the RNA levels of GAPDH, PSA, TMPRSS2:ERG and PCA3 in EPS specimens obtained from patients undergoing biopsy for prostate cancer. The level of PSA mRNA is significantly elevated in EPS specimens obtained from patients with a subsequent diagnosis of prostate cancer. This correlation influenced diagnostic testing results from EPS in two ways. First, when used as an exclusion parameter it appears to improve the diagnostic performance of TMPRSS2:ERG in EPS. Second, when used as a normalization parameter it appears to decrease the performance of these same tests. When comparing the results of mRNA based prostate cancer diagnostics in EPS it will be essential to consider PSA mRNA as a prostate specific gene and not a housekeeping gene.

  13. C-C motif ligand 5 promotes migration of prostate cancer cells in the prostate cancer bone metastasis microenvironment.

    PubMed

    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.

  14. Protocols for Migration and Invasion Studies in Prostate Cancer.

    PubMed

    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.

  15. The Diagnosis and Treatment of Prostate Cancer: A Review.

    PubMed

    Litwin, Mark S; Tan, Hung-Jui

    2017-06-27

    Prostate cancer is the most common cancer diagnosis made in men with more than 160 000 new cases each year in the United States. Although it often has an indolent course, prostate cancer remains the third-leading cause of cancer death in men. When prostate cancer is suspected, tissue biopsy remains the standard of care for diagnosis. However, the identification and characterization of the disease have become increasingly precise through improved risk stratification and advances in magnetic resonance and functional imaging, as well as from the emergence of biomarkers. Multiple management options now exist for men diagnosed with prostate cancer. Active surveillance (the serial monitoring for disease progression with the intent to cure) appears to be safe and has become the preferred approach for men with less-aggressive prostate cancer, particularly those with a prostate-specific antigen level of less than 10 ng/mL and Gleason score 3 + 3 tumors. Surgery and radiation continue to be curative treatments for localized disease but have adverse effects such as urinary symptoms and sexual dysfunction that can negatively affect quality of life. For metastatic disease, chemotherapy as initial treatment now appears to extend survival compared with androgen deprivation therapy alone. New vaccines, hormonal therapeutics, and bone-targeting agents have demonstrated efficacy in men with metastatic prostate cancer resistant to traditional hormonal therapy. Advances in the diagnosis and treatment of prostate cancer have improved the ability to stratify patients by risk and allowed clinicians to recommend therapy based on cancer prognosis and patient preference. Initial treatment with chemotherapy can improve survival compared with androgen deprivation therapy. Abiraterone, enzalutamide, and other agents can improve outcomes in men with metastatic prostate cancer resistant to traditional hormonal therapy.

  16. Macrophage Efferocytosis and Prostate Cancer Bone Metastasis

    DTIC Science & Technology

    2016-10-01

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

  17. Trichomonas vaginalis infection and risk of advanced prostate cancer.

    PubMed

    Shui, Irene M; Kolb, Suzanne; Hanson, Christi; Sutcliffe, Siobhan; Rider, Jennifer R; Stanford, Janet L

    2016-05-01

    The epidemiologic evidence for an association of Trichomonas vaginalis (Tv) with overall prostate cancer is mixed, but some studies suggest Tv may increase risk of more aggressive disease. The aim of this study was to assess whether Tv serostatus is associated with advanced or fatal prostate cancer. A total of 146 men with advanced (metastatic or fatal) prostate cancer and 181 age-matched controls were selected from two prior population-based, case-control studies. Tv serostatus was determined with the same laboratory methods used in previous epidemiologic studies. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression to compare Tv serostatus in prostate cancer cases and controls adjusted for potential confounders. The seroprevalence of Tv in controls was 23%. Tv serostatus was not associated with an increased risk of metastatic or fatal prostate cancer (ORs < 1). Our study does not support an increased risk of advanced or fatal prostate cancer in men seropositive for Tv. © 2016 Wiley Periodicals, Inc.

  18. The hedgehog/Gli signaling paradigm in prostate cancer

    PubMed Central

    Chen, Mengqian; Carkner, Richard; Buttyan, Ralph

    2011-01-01

    Hedgehog is a ligand-activated signaling pathway that regulates Gli-mediated transcription. Although most noted for its role as an embryonic morphogen, hyperactive hedgehog also causes human skin and brain malignancies. The hedgehog-related gene anomalies found in these tumors are rarely found in prostate cancer. Yet surveys of human prostate tumors show concordance of high expression of hedgehog ligands and Gli2 that correlate with the potential for metastasis and therapy-resistant behavior. Likewise, prostate cancer cell lines express hedgehog target genes, and their growth and survival is affected by hedgehog/Gli inhibitors. To date, the preponderance of data supports the idea that prostate tumors benefit from a paracrine hedgehog microenvironment similar to the developing prostate. Uncertainty remains as to whether hedgehog’s influence in prostate cancer also includes aspects of tumor cell autocrine-like signaling. The recent findings that Gli proteins interact with the androgen receptor and affect its transcriptional output have helped to identify a novel pathway through which hedgehog/Gli might affect prostate tumor behavior and raises questions as to whether hedgehog signaling in prostate cancer cells is suitably measured by the expression of Gli target genes alone. PMID:21776292

  19. Overview of Dietary Supplements in Prostate Cancer.

    PubMed

    Yacoubian, Aline; Dargham, Rana Abu; Khauli, Raja B; Bachir, Bassel G

    2016-11-01

    Prostate cancer is a key health concern for men with its etiology still under investigation. Recently, the role of dietary supplements has been noted to have a major inhibitory effect on prostate cancer and numerous studies have been conducted in this regard. This review provides a summary on numerous recent studies conducted in this field. Some of the studies reviewed revealed a protective role for supplements, and others showed no correlation while some even had an adverse effect. The mechanism of how these supplements act on the prostate is still not clear. Further studies are warranted especially for supplements that have been shown to have a potential inhibitory role in prostate cancer.

  20. Expression analysis of cancer-testis genes in prostate cancer reveals candidates for immunotherapy.

    PubMed

    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.

  1. The 24th Annual Prostate Cancer Foundation scientific retreat report.

    PubMed

    Miyahira, Andrea K; Soule, Howard R

    2018-05-15

    The 24th Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held from October 5-7, 2017, at the Omni Shoreham Hotel in Washington, DC. The PCF Scientific Retreat is a scientific conference that specifically focuses on cutting edge research deemed to have significant promise for accelerating advances in prostate cancer biology and treatment. Themes highlighted at this year's meeting included: (i) new understandings in prostate cancer biology and disease progression; (ii) new mechanisms and treatment targets in advanced prostate cancer; (iii) advances in precision medicine genomics, germline genetics, and selection of targeted therapies; (iv) PSMA-targeted agents for PET imaging and radionuclide therapy; (v) approaches for improving the efficacy of immunotherapy in prostate cancer; (vi) applications of 3D Genomics in prostate cancer research; and (vii) potential applications of artificial intelligence in prostate cancer. This article reviews the research presented at the PCF Scientific Retreat, in order to improve understanding of the current state of prostate cancer research, encourage discourse and exchange of novel ideas, and stimulate new basic, translational, and clinical research that will ultimately improve the lives of patients. © 2018 Wiley Periodicals, Inc.

  2. Relationship of urinary isoprostanes to prostate cancer occurrence.

    PubMed

    Brys, Magdalena; Morel, Agnieszka; Forma, Ewa; Krzeslak, Anna; Wilkosz, Jacek; Rozanski, Waldemar; Olas, Beata

    2013-01-01

    To estimate the oxidative stress in patients with prostate cancer and in a control group, we used the biomarker of lipid peroxidation-isoprostanes (8-isoPGF(2)) and the level of selected antioxidants (glucose and uric acid [UA]). The level of urinary isoprostanes was determined in patients and controls using an immunoassay kit according to the manufacturer's instruction. The levels of UA and glucose were also determined in serum by the use of UA Assay Kit and Glucose Assay Kit. We observed a statistically increased the level of isoprostanes in urine of patients with prostate cancer in compared with a control group. The concentration of tested antioxidants in blood from patients with prostate cancer was also higher than in healthy subjects. Moreover, our experiments indicate that the correlation between the increased amount of UA and the lipid peroxidation exists in prostate cancer patients (in all tested groups). Prostate cancer risk by urinary isoprostanes level was analyzed, and a positive association was found (relative risk for highest vs. lowest quartile of urinary isoprostanes = 1.6; 95 % confidence interval 1.2-2.4; p for trend = 0.03). We suggest that reactive oxygen species induce peroxidation of unsaturated fatty acid in patients with prostate cancer, and the level of isoprostanes may be used as a non-invasive marker for determination of oxidative stress. We also propose that UA may enhance the oxidative stress in patients with prostate cancer.

  3. Incidental Metastatic Melanoma Identified on 68Ga-Prostate-Specific Membrane Antigen PET/CT for Metastatic Prostate Cancer.

    PubMed

    Snow, Hayden A; Hofman, Michael S; Mitchell, Catherine A; Gyorki, David E; Smith, Myles J F

    2018-07-01

    A 78-year-old man with a history of surgically treated prostate cancer and melanoma underwent Ga-prostate-specific membrane antigen (PSMA) PET/CT for biochemical recurrence of his prostate cancer. This revealed locoregionally recurrent prostate cancer and a separate PSMA-avid nodule in his left arm. Subsequent F-FDG PET/CT and excision confirmed this to be an in-transit melanoma metastasis. Prostate-specific membrane antigen PET/CT has become a widely used and valuable tool in the assessment of prostate cancer, particularly biochemically recurrent. Uptake of PSMA has been described in a multitude of different benign and malignant conditions, but it has only rarely been documented in melanoma.

  4. Super-Penetrant Androgen Receptor: Overcoming Enzalutamide Sensitivity in Castration-Resistant Prostate Cancer

    DTIC Science & Technology

    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

  5. AR Signaling in Human Malignancies: Prostate Cancer and Beyond.

    PubMed

    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.

  6. Autoantibody signatures as biomarkers to distinguish prostate cancer from benign prostatic hyperplasia in patients with increased serum prostate specific antigen.

    PubMed

    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.

  7. Focal Cryotherapy for Localized Prostate Cancer.

    PubMed

    Tay, K J; Polascik, T J

    2016-07-01

    To systematically review the oncological and functional outcomes of contemporary primary prostate focal cryotherapy for localized prostate cancer in the context of current developments in prostate focal therapy. We performed a systematic search of the Pubmed, Cochrane and Embase databases to identify studies where primary prostate focal cryotherapy was performed to treat prostate cancer. These included reports on focal/ lesion/ sector ablation, hemi-ablation and partial prostate ablation. We excluded salvage focal therapy studies. Where multiple reports were published over time from a single cohort, the latest one was used. Our search yielded 290 publications, including 17 primary reports on eight single-center cohort studies and one multi-center registry report. Of 1,595 men identified, mean age was 60.5-69.5 years and mean PSA 5.1-7.8 ng/ml. When stratified by D'Amico risk criteria, 52% of the aggregate total number of men were low-risk, 38% intermediate-risk and 10% high-risk. Besides 12-core TRUS biopsy, 3 cohorts reported using TTMB and one included mpMRI to select men for focal treatment. Median follow-up ranged from 13-63 months. BPFS ranged from 71-98%. The overall post-treatment positive biopsy rate was 8-25%. Among 5 cohorts with a mandatory 6-12 month posttreatment biopsy, 216 of 272 men (79%) did undergo biopsy, with 47 positive (21.8%). Of these, 15 were infield, 26 outfield, 2 bilateral and 4 undeclared. Ten upgraded to Gleason≥7. Overall, two men had metastatic disease and none died of prostate cancer. Post-treatment continence rates were 96-100% and rates of erectile dysfunction ranged from 0-42%. The rate of post-treatment urinary retention ranged from 0-15%. The rate of recto-urethral fistula was 0-0.1%. Focal cryotherapy for localized prostate cancer is a safe and provides good preservation of sexual and urinary function. Accurate cancer localization and risk stratification is key to patient selection. In highly selected patients, focal therapy

  8. Alcohol consumption and prostate cancer: a mini review.

    PubMed

    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.

  9. Prostate cancer incidence in Australia correlates inversely with solar radiation.

    PubMed

    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

  10. DNA Methylation in Promoter Region as Biomarkers in Prostate Cancer

    PubMed Central

    Yang, Mihi; Park, Jong Y.

    2013-01-01

    The prostate gland is the most common site of cancer and the second leading cause of cancer death in American men. Recent emerging molecular biological technologies help us to know that epigenetic alterations such as DNA methylation within the regulatory (promoter) regions of genes are associated with transcriptional silencing in cancer. Promoter hypermethylation of critical pathway genes could be potential biomarkers and therapeutic targets for prostate cancer. In this chapter, we updated current information on methylated genes associated with the development and progression of prostate cancer. Over 40 genes have been investigated for methylation in promoter region in prostate cancer. These methylated genes are involved in critical pathways, such as DNA repair, metabolism, and invasion/metastasis. The role of hypermethylated genes in regulation of critical pathways in prostate cancer is discussed. These findings may provide new information of the pathogenesis, the exciting potential to be predictive and to provide personalized treatment of prostate cancer. Indeed, some epigenetic alterations in prostate tumors are being translated into clinical practice for therapeutic use. PMID:22359288

  11. Evaluating genetic risk for prostate cancer among Japanese and Latinos

    PubMed Central

    Cheng, Iona; Chen, Gary K.; Nakagawa, Hidewaki; He, Jing; Wan, Peggy; Laurie, Cathy; Shen, Jess; Sheng, Xin; Pooler, Loreall C.; Crenshaw, Andrew T.; Mirel, Daniel B.; Takahashi, Atsushi; Kubo, Michiaki; Nakamura, Yusuke; Al Olama, Ali Amin; Benlloch, Sara; Donovan, Jenny L.; Guy, Michelle; Hamdy, Freddie C.; Kote-Jarai, Zsofia; Neal, David E.; Wilkens, Lynne R.; Monroe, Kristine R.; Stram, Daniel O.; Muir, Kenneth; Eeles, Rosalind A.; Easton, Douglas F.; Kolonel, Laurence N.; Henderson, Brian E.; Le Marchand, Loïc; Haiman, Christopher A.

    2012-01-01

    Background There have been few genome-wide association studies (GWAS) of prostate cancer among diverse populations. To search for novel prostate cancer risk variants, we conducted GWAS of prostate cancer in Japanese and Latinos. In addition, we tested prostate cancer risk variants and developed genetic risk models of prostate cancer for Japanese and Latinos. Methods Our first stage GWAS of prostate cancer included Japanese (cases/controls=1,033/1,042) and Latino (cases/controls=1,043/1,057) from the Multiethnic Cohort. Significant associations from stage 1 (P < 1.0×10−4) were examined in silico in GWAS of prostate cancer (stage 2) in Japanese (cases/controls=1,583/3,386) and Europeans (cases/controls=1,854/1,894). Results No novel stage 1 SNPs outside of known risk regions reached genome-wide significance. For Japanese, in stage 1, the most notable putative novel association was seen with 10 SNPs (P<8.0. x10−6) at chromosome 2q33; however, this was not replicated in stage 2. For Latinos, the most significant association was observed with rs17023900 at the known 3p12 risk locus (stage 1: OR=1.45; P=7.01×10−5 and stage 2: OR=1.58; P =3.05×10−7). The majority of the established risk variants for prostate cancer, 79% and 88%, were positively associated with prostate cancer in Japanese and Latinos (stage I), respectively. The cumulative effects of these variants significantly influence prostate cancer risk (OR per allele=1.10; P = 2.71×10−25 and OR=1.07; P = 1.02×10−16 for Japanese and Latinos, respectively). Conclusion and Impact Our GWAS of prostate cancer did not identify novel genome-wide significant variants. However, our findings demonstrate that established risk variants for prostate cancer significantly contribute to risk among Japanese and Latinos. PMID:22923026

  12. Evaluating genetic risk for prostate cancer among Japanese and Latinos.

    PubMed

    Cheng, Iona; Chen, Gary K; Nakagawa, Hidewaki; He, Jing; Wan, Peggy; Laurie, Cathy C; Shen, Jess; Sheng, Xin; Pooler, Loreall C; Crenshaw, Andrew T; Mirel, Daniel B; Takahashi, Atsushi; Kubo, Michiaki; Nakamura, Yusuke; Al Olama, Ali Amin; Benlloch, Sara; Donovan, Jenny L; Guy, Michelle; Hamdy, Freddie C; Kote-Jarai, Zsofia; Neal, David E; Wilkens, Lynne R; Monroe, Kristine R; Stram, Daniel O; Muir, Kenneth; Eeles, Rosalind A; Easton, Douglas F; Kolonel, Laurence N; Henderson, Brian E; Le Marchand, Loïc; Haiman, Christopher A

    2012-11-01

    There have been few genome-wide association studies (GWAS) of prostate cancer among diverse populations. To search for novel prostate cancer risk variants, we conducted GWAS of prostate cancer in Japanese and Latinos. In addition, we tested prostate cancer risk variants and developed genetic risk models of prostate cancer for Japanese and Latinos. Our first-stage GWAS of prostate cancer included Japanese (cases/controls = 1,033/1,042) and Latino (cases/controls = 1,043/1,057) from the Multiethnic Cohort (MEC). Significant associations from stage I (P < 1.0 × 10(-4)) were examined in silico in GWAS of prostate cancer (stage II) in Japanese (cases/controls = 1,583/3,386) and Europeans (cases/controls = 1,854/1,894). No novel stage I single-nucleotide polymorphism (SNP) outside of known risk regions reached genome-wide significance. For Japanese, in stage I, the most notable putative novel association was seen with 10 SNPs (P ≤ 8.0 × 10(-6)) at chromosome 2q33; however, this was not replicated in stage II. For Latinos, the most significant association was observed with rs17023900 at the known 3p12 risk locus (stage I: OR = 1.45; P = 7.01 × 10(-5) and stage II: OR = 1.58; P = 3.05 × 10(-7)). The majority of the established risk variants for prostate cancer, 79% and 88%, were positively associated with prostate cancer in Japanese and Latinos (stage I), respectively. The cumulative effects of these variants significantly influence prostate cancer risk (OR per allele = 1.10; P = 2.71 × 10(-25) and OR = 1.07; P = 1.02 × 10(-16) for Japanese and Latinos, respectively). Our GWAS of prostate cancer did not identify novel genome-wide significant variants. However, our findings show that established risk variants for prostate cancer significantly contribute to risk among Japanese and Latinos. ©2012 AACR.

  13. Predictors of participation in prostate cancer screening at worksites.

    PubMed

    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.

  14. Imaging Prostate Cancer Microenvironment by Collagen Hybridization

    DTIC Science & Technology

    2016-12-01

    2: Evaluation of 18F-DCFPyL labelling and tracking of PSMA+ CAR T cells Title: PSMA Directed Imaging of Prostate Cancer Focus on Androgen Receptor ... receptors to treat cancer Title: Plasmid Selection and Characterisation Time Commitments: 1.20 calendar months Supporting Agency: Cancer Targeting...AWARD NUMBER: W81XWH-12-1-0556 TITLE: Imaging Prostate Cancer Microenvironment by Collagen Hybridization PRINCIPAL INVESTIGATOR: Martin

  15. Tissue-based biomarkers in prostate cancer

    PubMed Central

    Clinton, Timothy N.; Bagrodia, Aditya; Lotan, Yair; Margulis, Vitaly; Raj, Ganesh V; Woldu, Solomon L

    2017-01-01

    Introduction Prostate cancer is a heterogeneous disease. Existing risk stratification tools based on standard clinlicopathologic variables (prostate specific antigen [PSA], Gleason score, and tumor stage) provide a modest degree of predictive ability. Advances in high-throughput sequencing has led to the development of several novel tissue-based biomarkers that can improve prognostication in prostate cancer management. Areas Covered The authors review commercially-available, tissue-based biomarker assays that improve upon existing risk-stratification tools in several areas of prostate cancer management, including the appropriateness of active surveillance and aiding in decision making regarding the use of adjuvant therapy. Additionally, some of the obstacles to the widespread adoption of these biomarkers and discuss several investigational sources of new biomarkers are discussed. Expert Commentary Work is ongoing to answer pertinent clinical questions in prostate cancer management including which patients should undergo biopsy, active surveillance, receive adjuvant therapy, and what systemic therapy is best in the first-line. Incorporation into novel biomarkers may allow for the incorporation of a ‘personalized’ approach to management. Further validation will be required and questions of cost must be considered before wide scale adoption of these biomarkers. Tumor heterogeneity may impose a ceiling on the prognostic ability of biomarkers using currently available techniques. PMID:29226251

  16. Lycopene, tomato products and prostate cancer-specific mortality among men diagnosed with nonmetastatic prostate cancer in the Cancer Prevention Study II Nutrition Cohort.

    PubMed

    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 < median. Future studies are needed to confirm the potential inverse association of consistently high lycopene intake with PCSM among men with high-risk prostate cancers. © 2016 UICC.

  17. Educating men about prostate cancer in the workplace.

    PubMed

    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.

  18. Prostate Cancer Research Training Program

    DTIC Science & Technology

    2017-09-01

    Award Number: W81XWH-16-1-0549 TITLE: Prostate Cancer Research Training Program PRINCIPAL INVESTIGATOR: David M. Lubaroff, PhD CONTRACTING...ORGANIZATION: University of Iowa Iowa City, IA 52242 REPORT DATE: September 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research ...Prostate Cancer Research Training Program 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0549 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

  19. Vaccine Immunotherapy for Prostate Cancer

    DTIC Science & Technology

    2012-05-01

    adenovirus/PSA (Ad/PSA) vaccine for the treatment of prostate cancer. Two protocols have been used in the trial: #1 - Phase II study of Adenovirus/PSA...this award is to conduct a Phase II clinical trial (Study) of an adenovirus/PSA (Ad/PSA) vaccine for the treatment of prostate cancer. Two protocols...suddenly prior to study treatment . And one patient previously reported as a screen failure became eligible and was treated. This subject was not

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

    PubMed

    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.

  1. Molecular Characterization of Indolent Prostate Cancer

    DTIC Science & Technology

    2013-10-01

    SUPPLEMENTARY NOTES 14. ABSTRACT Indolent prostate cancers that pose very low risk to aged men occur frequently and may be detected at biopsy, leading...Introduction Indolent prostate cancers that pose very low risk to aged men occur frequently and may be detected at biopsy, leading to the...cancer at the time of biopsy detection and thus meeting the entry criteria for active surveillance. The scope of the proposed research is: 1) to

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

    PubMed

    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.

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

    PubMed Central

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

    2015-01-01

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

  4. Screening for prostate cancer: estimating the magnitude of overdetection

    PubMed Central

    McGregor, M; Hanley, J A; Boivin, J F; McLean, R G

    1998-01-01

    BACKGROUND: No randomized controlled trial of prostate cancer screening has been reported and none is likely to be completed in the near future. In the absence of direct evidence, the decision to screen must therefore be based on estimates of benefits and risks. The main risk of screening is overdetection--the detection of cancer that, if left untreated, would not cause death. In this study the authors estimate the level of overdetection that might result from annual screening of men aged 50-70. METHODS: The annual rate of lethal screen-detectable cancer (detectable cancer that would prove fatal before age 85 if left untreated) was calculated from the observed prostate cancer mortality rate in Quebec; the annual rate of all cases of screen-detectable prostate cancer was calculated from 2 recent screening studies. RESULTS: The annual rate of lethal screen-detectable prostate cancer was estimated to be 1.3 per 1000 men. The annual rate of all cases of screen-detectable prostate cancer was estimated to be 8.0 per 1000 men. The estimated case-fatality rate among men up to 85 years of age was 16% (1.3/8.0) (sensitivity analysis 13% to 22%). INTERPRETATION: Of every 100 men with screen-detected prostate cancer, only 16 on average (13 to 22) could have their lives extended by surgery, since the prostate cancer would not cause death before age 85 in the remaining 84 (78 to 87). PMID:9861205

  5. Intraductal Carcinoma of the Prostate on Diagnostic Needle Biopsy Predicts Prostate Cancer Mortality: A Population-Based Study.

    PubMed

    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 < 0.005). The presence of IDC-P on diagnostic needle biopsy remained an independent predictor of 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

  6. Brachytherapy for Prostate Cancer: A Systematic Review

    PubMed Central

    Koukourakis, Georgios; Kelekis, Nikolaos; Armonis, Vassilios; Kouloulias, Vassilios

    2009-01-01

    Low-dose rate brachytherapy has become a mainstream treatment option for men diagnosed with prostate cancer because of excellent long-term treatment outcomes in low-, intermediate-, and high-risk patients. To a great extend due to patient lead advocacy for minimally invasive treatment options, high-quality prostate implants have become widely available in the US, Europe, and Japan. High-dose-rate (HDR) afterloading brachytherapy in the management of localised prostate cancer has practical, physical, and biological advantages over low-dose-rate seed brachytherapy. There are no free live sources used, no risk of source loss, and since the implant is a temporary procedure following discharge no issues with regard to radioprotection use of existing facilities exist. Patients with localized prostate cancer may benefit from high-dose-rate brachytherapy, which may be used alone in certain circumstances or in combination with external-beam radiotherapy in other settings. The purpose of this paper is to present the essentials of brachytherapies techniques along with the most important studies that support their effectiveness in the treatment of prostate cancer. PMID:19730753

  7. Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate

    USDA-ARS?s Scientific Manuscript database

    Introduction: A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (1). The present study evaluates serum and prostate tissue folate levels in men with prostate cancer, compared to histologically normal prostate glands from can...

  8. Prostate Specific Membrane Antigen (PSMA) Targeted Bio-orthogonal Therapy for Metastatic Prostate Cancer

    DTIC Science & Technology

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0595 TITLE: Prostate-Specific Membrane Antigen (PSMA) Targeted Bio -orthogonal Therapy for Metastatic Prostate Cancer...Sep 2016 - 14 Sep 2017 4. TITLE AND SUBTITLE Prostate-Specific Membrane Antigen (PSMA) Targeted Bio -orthogonal Therapy for Metastatic Prostate

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

    USDA-ARS?s Scientific Manuscript database

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

  10. Raman spectroscopy for prostate cancer detection and characterization (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Aubertin, Kelly; Trinh, Quoc-Huy; Jermyn, Michael; St-Pierre, Catherine; Vladoiu, Maria-Claudia; Grosset, Andrée.-Anne; Saad, Fred; Trudel, Dominique; Leblond, Frédéric

    2017-02-01

    Prostate cancer is the most frequent diagnosed cancers among men. When prostate cancer occurs, the cancer does not result in only one or few localized malignant tumor, but is generally spread within the whole prostate. In order to counteract the very high level of heterogeneities exhibited by prostate tissues, we developed a method for high-resolution co-registration of Raman spectroscopy with prostate cancer diagnosis. Raman spectra were acquired on fresh ex vivo prostate within 2 hours after radical prostatectomy using a multi-wavelength hand-held contact probe. After the measurements, the prostate was reintegrated to the usual pathological workflow: formalin fixated and paraffin embedded (FFPE), and prepared for microscope histopathological analyses. The precise reconstruction of the prostate slice with hematoxylin and eosin (H and E) tissue allows the spatial correlation of the measured area (0.2 mm2) with the correspondent histopathological information, for point-by-point diagnosis determination. The tissue was classified into groups (normal/cancer) and subgroups according to the percentage of benign glands, stroma or cancer. Different machine learning algorithms were tested to classify the spectra with increasing levels of categorization. Preliminary results showed that Raman spectroscopy is capable of detecting prostate cancer with an accuracy >90%. In addition, high percentages of stroma (vs. glands) have been correlated with spectral signature of collagen, which is the main constituent of extracellular matrix.

  11. Prostate Cancer, Nutrition, and Dietary Supplements (PDQ®)—Patient Version

    Cancer.gov

    Prostate Cancer, Nutrition, and Dietary Supplements summary discusses the use of nutrition and dietary supplements for preventing or treating prostate cancer. Learn more about the use of complementary therapies for prostate cancer in this expert-reviewed summary.

  12. Imaging of Prostate Cancer Using Gallium-68-Labeled Bombesin.

    PubMed

    Sonni, Ida; Baratto, Lucia; Iagaru, Andrei

    2017-04-01

    Nuclear medicine can play an important role in evaluating prostate cancer combining anatomical and functional information with hybrid techniques. Various PET radiopharmaceuticals have been used for targeting specific biological markers in prostate cancer. Research is ideally oriented towards the development of radiopharmaceuticals targeting antigens overexpressed in prostate cancer, as opposed to normal prostate tissue. In this regard, gastrin-releasing peptide receptors (GRPR) are excellent candidates. Bombesin analogues targeting the GRPR have been investigated. Gallium-68 ( 68 Ga) is an interesting PET radioisotope due to several advantages, such as availability, ease of radiochemistry, half-life, and costs. The focus of this review is on 68 Ga-labeled bombesin analogues in prostate cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Ciprofloxacin as a prophylactic agent against prostate cancer: a "two hit" hypothesis.

    PubMed

    Kloskowski, T; Gurtowska, N; Bajek, A; Drewa, T

    2012-02-01

    More evidence indicate that prostate inflammation can lead to prostate cancer development. Prostate cancer affects elderly men. Prostate cancer prophylaxis is an important issue because life expectancy is very long now. Ciprofloxacin is an antibacterial agent used mainly in urinary tract infections and prostate inflammation. This drug acts also against cancer cells by the inhibition of topoisomerase II. These properties should allow it to inhibit the development of prostate cancer. Firstly, ciprofloxacin can stop the acute and chronic prostate inflammation which can lead to cancer development. Secondly, ciprofloxacin can potentially kill prostate cancer cells in their early stage of development. Ciprofloxacin accumulates mainly in the prostate after oral intake thus ciprofloxacin seems to be a perfect candidate as a prophylactic agent. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Recruitment of African Americans into prostate cancer screening.

    PubMed

    Weinrich, S P; Boyd, M D; Bradford, D; Mossa, M S; Weinrich, M

    1998-01-01

    Both incidence and mortality rates for prostate cancer are significantly higher in African American men than in white men. This report identifies community sites for the optimal recruitment of African American men into prostate cancer screening. A descriptive study was conducted, providing an educational program to 1369 African American men, 1264 of whom completed a survey on demographic data, prostate cancer knowledge, and prostate cancer screening history. The programs were offered at six different types of community sites, including various work sites, churches, housing projects, National Association for Advancement of Colored Persons (NAACP) sites, barber shops, and a state fairground. Free prostate cancer screening was offered to all participants. The advertised mass screening site (state fairground), the most common method used nationally to recruit African American men for cancer screening, was the least effective site, with only 16 men completing the survey. Of the 1264 men completing the survey at all community sites, 597 men (47%) did so at work sites and 438 (35%) did so at churches. Per site, the largest percentage of men who had never been screened was at work sites (n = 276, 46%) and NAACP sites (n = 22, 33.8%). The highest percentage of men who obtained free screening were at the state fairground (14 of 16), churches (256 of 438), and work sites (336 of 597). The most prostate cancers were detected at the housing projects, where 3 of 38 (7.9%) men who were screened received diagnoses of prostate cancer. To reduce prostate mortality rates in African American men, healthcare providers need to make a concerted effort to increase prostate cancer education and screening in this population. To be effective, recruitment of African American men must move from a provider/health site orientation to a consumer/community orientation. These findings indicate that recruitment strategies are more successful if efforts are based in the community or where a large

  15. Cabazitaxel Plus Prednisone With Octreotide For Castration-Resistant Prostate Cancer (CRPC) Previously Treated With Docetaxel

    ClinicalTrials.gov

    2014-11-21

    Diarrhea; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage IV Prostate Cancer

  16. Targeting Btk/Etk of prostate cancer cells by a novel dual inhibitor

    PubMed Central

    Guo, W; Liu, R; Bhardwaj, G; Yang, J C; Changou, C; Ma, A-H; Mazloom, A; Chintapalli, S; Xiao, K; Xiao, W; Kumaresan, P; Sanchez, E; Yeh, C-T; Evans, C P; Patterson, R; Lam, K S; Kung, H-J

    2014-01-01

    Btk and Etk/BMX are Tec-family non-receptor tyrosine kinases. Btk has previously been reported to be expressed primarily in B cells and has an important role in immune responses and B-cell malignancies. Etk has been shown previously to provide a strong survival and metastasis signal in human prostate cancer cells, and to confer androgen independence and drug resistance. While the role of Etk in prostate carcinogenesis is well established, the functions of Btk in prostate cancer have never been investigated, likely due to the perception that Btk is a hematopoietic, but not epithelial, kinase. Herein, we found that Btk is overexpressed in prostate cancer tissues and prostate cancer cells. The level of Btk in prostate cancer tissues correlates with cancer grades. Knockdown of Btk expression selectively inhibits the growth of prostate cancer cells, but not that of the normal prostate epithelial cells, which express very little Btk. Dual inhibition of Btk and Etk has an additive inhibitory effect on prostate cancer cell growth. To explore Btk and Etk as targets for prostate cancer, we developed a small molecule dual inhibitor of Btk and Etk, CTN06. Treatment of PC3 and other prostate cancer cells, but not immortalized prostate epithelial cells with CTN06 resulted in effective cell killing, accompanied by the attenuation of Btk/Etk signals. The killing effect of CTN06 is more potent than that of commonly used inhibitors against Src, Raf/VEGFR and EGFR. CTN06 induces apoptosis as well as autophagy in human prostate cancer cells, and is a chemo-sensitizer for docetaxel (DTX), a standard of care for metastatic prostate cancer patients. CTN06 also impeded the migration of human prostate cancer cells based on a ‘wound healing' assay. The anti-cancer effect of CTN06 was further validated in vivo in a PC3 xenograft mouse model. PMID:25188519

  17. Targeting Btk/Etk of prostate cancer cells by a novel dual inhibitor.

    PubMed

    Guo, W; Liu, R; Bhardwaj, G; Yang, J C; Changou, C; Ma, A-H; Mazloom, A; Chintapalli, S; Xiao, K; Xiao, W; Kumaresan, P; Sanchez, E; Yeh, C-T; Evans, C P; Patterson, R; Lam, K S; Kung, H-J

    2014-09-04

    Btk and Etk/BMX are Tec-family non-receptor tyrosine kinases. Btk has previously been reported to be expressed primarily in B cells and has an important role in immune responses and B-cell malignancies. Etk has been shown previously to provide a strong survival and metastasis signal in human prostate cancer cells, and to confer androgen independence and drug resistance. While the role of Etk in prostate carcinogenesis is well established, the functions of Btk in prostate cancer have never been investigated, likely due to the perception that Btk is a hematopoietic, but not epithelial, kinase. Herein, we found that Btk is overexpressed in prostate cancer tissues and prostate cancer cells. The level of Btk in prostate cancer tissues correlates with cancer grades. Knockdown of Btk expression selectively inhibits the growth of prostate cancer cells, but not that of the normal prostate epithelial cells, which express very little Btk. Dual inhibition of Btk and Etk has an additive inhibitory effect on prostate cancer cell growth. To explore Btk and Etk as targets for prostate cancer, we developed a small molecule dual inhibitor of Btk and Etk, CTN06. Treatment of PC3 and other prostate cancer cells, but not immortalized prostate epithelial cells with CTN06 resulted in effective cell killing, accompanied by the attenuation of Btk/Etk signals. The killing effect of CTN06 is more potent than that of commonly used inhibitors against Src, Raf/VEGFR and EGFR. CTN06 induces apoptosis as well as autophagy in human prostate cancer cells, and is a chemo-sensitizer for docetaxel (DTX), a standard of care for metastatic prostate cancer patients. CTN06 also impeded the migration of human prostate cancer cells based on a 'wound healing' assay. The anti-cancer effect of CTN06 was further validated in vivo in a PC3 xenograft mouse model.

  18. Coffee and tea consumption in relation to prostate cancer prognosis

    PubMed Central

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

    2013-01-01

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

  19. CHK2, A Candidate Prostate Cancer Susceptibility Gene

    DTIC Science & Technology

    2005-01-01

    novel FBN1 mutations, polymor- 1298-1304 phisms, and sequence variants in Marfan syndrome and re- Boddy MN, Furnari B, Mondesert 0, Russell P (1998...2001) or have suggested only a limited prone syndromes , such as Li-Fraumeni syndrome (LFS role in hereditary prostate cancer (Rebbeck et al. 2000...prostate cancer or other malig- with prostate cancer carried the Ile157Thr mutation. nancies occurring in LFS or LFS-like syndromes later in However

  20. Mesenchymal Stem Cell Based Therapy for Prostate Cancer

    DTIC Science & Technology

    2015-11-01

    Award Number: W81XWH-13-1-0304 TITLE: Mesenchymal Stem Cell-Based Therapy for Prostate Cancer PRINCIPAL INVESTIGATOR: John Isaacs CONTRACTING...TITLE AND SUBTITLE Mesenchymal Stem Cell-Based Therapy for Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0304 5c. PROGRAM ELEMENT...effective therapy for castrate resistant metastatic prostate cancer (CRPC). Based upon a substantial published literature from multiple groups, as well as

  1. PHI in the Early Detection of Prostate Cancer.

    PubMed

    Fuchsova, Radka; Topolcan, Ondrej; Windrichova, Jindra; Hora, Milan; Dolejsova, Olga; Pecen, Ladislav; Kasik, Petr; Novak, Jaroslav; Casova, Miroslava; Smejkal, Jiri

    2015-09-01

    To evaluate changes in the serum levels of prostate specific antigen (PSA), %free PSA and -2proPSA biomarkers, and prostate health index (PHI) in the diagnostic algorithm of early prostate cancer. The Immunoanalytical Laboratory of the University Hospital in Pilsen examined sera from 263 patients being treated at the Hospital's Urology Department with suspected prostate cancer who had undergone biopsies and were divided into a benign and malignant group. The monitored biomarkers were measured using chemiluminescence. All statistical analyses were calculated using the SAS software. We found statistically significantly increased levels of -2proPSA, PHI and PSA and decreased levels of %freePSA in patients diagnosed with prostate cancer by prostate biopsy vs. patients with benign prostatic hypertrophy (median values: -2proPSA: 16 vs. 21 ng/l, PHI: 35 vs. 62, total PSA: 7.2 vs. 7.7 μg/l and %free PSA: 16.7 vs. 11.7%). Receiver operating characteristic curves showed the best performance for PHI compared to other markers. The assessment of -2proPSA and the calculation of PHI appear to be of great benefit for a more accurate differential diagnosis of benign hyperplasia and prostate cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  2. Screening spectroscopy of prostate cancer

    NASA Astrophysics Data System (ADS)

    Yermolenko, S. B.; Voloshynskyy, D. I.; Fedoruk, O. S.

    2015-11-01

    The aim of the study was to establish objective parameters of the field of laser and incoherent radiation of different spectral ranges (UV, visible, IR) as a non-invasive optical method of interaction with different samples of biological tissues and fluids of patients to determine the state of prostate cancer and choosing the best personal treatment. The objects of study were selected venous blood plasma of patient with prostate cancer, histological sections of rat prostate gland in the postoperative period. As diagnostic methods have been used ultraviolet spectrometry samples of blood plasma in the liquid state, infrared spectroscopy middle range (2,5-25 microns) dry residue of plasma by spectral diagnostic technique of thin histological sections of biological tissues.

  3. Proposed morphologic classification of prostate cancer with neuroendocrine differentiation.

    PubMed

    Epstein, Jonathan I; Amin, Mahul B; Beltran, Himisha; Lotan, Tamara L; Mosquera, Juan-Miguel; Reuter, Victor E; Robinson, Brian D; Troncoso, Patricia; Rubin, Mark A

    2014-06-01

    On July 31, 2013, the Prostate Cancer Foundation assembled a working committee on the molecular biology and pathologic classification of neuroendocrine (NE) differentiation in prostate cancer. New clinical and molecular data emerging from prostate cancers treated by contemporary androgen deprivation therapies, as well as primary lesions, have highlighted the need for refinement of diagnostic terminology to encompass the full spectrum of NE differentiation. The classification system consists of: Usual prostate adenocarcinoma with NE differentiation; 2) Adenocarcinoma with Paneth cell NE differentiation; 3) Carcinoid tumor; 4) Small cell carcinoma; 5) Large cell NE carcinoma; and 5) Mixed NE carcinoma - acinar adenocarcinoma. The article also highlights "prostate carcinoma with overlapping features of small cell carcinoma and acinar adenocarcinoma" and "castrate-resistant prostate cancer with small cell cancer-like clinical presentation". It is envisioned that specific criteria associated with the refined diagnostic terminology will lead to clinically relevant pathologic diagnoses that will stimulate further clinical and molecular investigation and identification of appropriate targeted therapies.

  4. [Prostate cancer. Epidemiology. Risk factors. Pathology].

    PubMed

    Fournier, G; Valeri, A; Mangin, P; Cussenot, O

    2004-10-01

    Prostate cancer (prostate adenocarcinoma) has become an important concern in terms of public health these past fifteen years; recent French epidemiological data revealed 10,104 deaths due to this disease in 2000. The two main factors involved are the serum prostatic specific antigen (PSA), routinely used since late 1980's and which allows early diagnosis (before symptom onset), and the lengthened duration of life. Such cancer is rare before the age of 50, but its frequency increases with age, making it the most frequent type of cancer in French men. Although the aetiology of this disease is unknown, the ethnic origin, and a familial history of prostate or breast cancer are known risk factors. Predisposing genes to such hereditary types remain to be identified. Other genetic factors (polymorphisms), combined with environmental factors such as nutrition, have been incriminated, which is likely to explain the geographical variations of this affection. At the molecular level, the mechanisms involved in the tumoral initiation and progression remain unclear. Various genetic alterations have been identified among the genome of cancerous cells, at various stages of the affection: intraepithelial neoplasia, localized, locally advanced, metastatic or hormone refractory stage -, hormonal escape). However, the precise sequence and nature of the complex molecular events remain to be determined prior to their routine utilisation in the determination of subjects at risk, or as prognostic factors, and even as therapeutic targets. The anatomopathology is a key for the diagnosis. Intraepithelial neoplasia is the pre-cancerous lesion observed in most adenocarcinomas; these are localized in the peripheral part of the prostate gland in 70% of the cases. Gleason's classification is the current gold standard for the determination of tumoral aggressiveness and categorisation of the adenocarcinomas which are basically heterogeneous (coexistence of tumors cells with different degrees of

  5. Molecular and Clinical Predictors of Aggressive Prostate Cancer

    DTIC Science & Technology

    2008-09-01

    Trichomonas vaginalis and subsequent risk of prostate cancer. Cancer Epidemiology Biomarkers and Prevention 2006;15: 939-45. 12. Urisman A, Molinaro...combined with the findings of serologic evidence of T vaginalis and prostate cancer mortality provide supportive evidence for the study hypothesis

  6. Association of Androgen Metabolism Gene Polymorphisms with Prostate Cancer Risk and Androgen Concentrations: Results from the Prostate Cancer Prevention Trial

    PubMed Central

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

    2016-01-01

    Background Prostate cancer is highly influenced by androgens and genes. We investigated whether genetic polymorphisms along the androgen biosynthesis and metabolism pathways are associated with androgen concentrations or risk of prostate cancer or high-grade disease from finasteride treatment. Methods A nested case-control study from the Prostate Cancer Prevention Trial using cases drawn from men with biopsy-proven prostate cancer and biopsy-negative, frequency-matched controls was conducted to investigate the association of 51 single nucleotide polymorphisms (SNPs) in 12 genes of the androgen pathway with total, low-grade, and high-grade prostate cancer incidence and serum hormone concentrations. Results There were significant associations of genetic polymorphisms in SRD5A1 (rs3736316, rs3822430, rs1560149, rs248797, and rs472402) and SRD5A2 (rs2300700) with risk of high-grade prostate cancer in the placebo arm of the PCPT; two SNPs were significantly associated with increased risk (SRD5A1 rs472402 [OR, 1.70; 95% CI, 1.05-2.75, Ptrend=0.03]; SRD5A2 rs2300700 [OR, 1.94; 95% CI, 1.19-3.18, Ptrend=0.01]). Eleven SNPs in SRD5A1, SRD5A2, CYP1B1, and CYP3A4 were found to be associated with modifying mean serum androgen and sex hormone-binding globulin concentrations; two SNPs (SRD5A1 rs824811 and CYP1B1 rs10012, Ptrend<0.05) consistently and significantly altered all androgen concentrations. Several SNPs (rs3822430, rs2300700; CYP3A43 rs800672; CYP19 rs700519; Ptrend<0.05) were significantly associated with both circulating hormone levels and prostate cancer risk. Conclusion Germline genetic variations of androgen-related pathway genes are associated with serum androgen concentrations and risk of prostate cancer. Further studies to examine the functional consequence of novel causal variants are warranted. PMID:27164191

  7. Dietary acrylamide and risk of prostate cancer.

    PubMed

    Wilson, Kathryn M; Giovannucci, Edward; Stampfer, Meir J; Mucci, Lorelei A

    2012-07-15

    Acrylamide has been designated by IARC as a "probable human carcinogen." High levels are formed during cooking of many commonly consumed foods including French fries, potato chips, breakfast cereal and coffee. Two prospective cohort studies and two case-control studies in Europe found no association between acrylamide intake and prostate cancer. We examined this association in a large prospective cohort of 47,896 US men in the Health Professionals' Follow-up Study, using updated dietary acrylamide intake from food frequency questionnaires in 1986, 1990, 1994, 1998 and 2002. From 1986 through 2006, we documented 5025 cases of prostate cancer, and 642 lethal cancers. We used Cox proportional hazards models to assess the association between acrylamide intake from diet and prostate cancer risk overall as well as risk of advanced or lethal cancer. Acrylamide intake ranged from a mean of 10.5 mcg/day in the lowest quintile to 40.1 mcg/day in the highest quintile; coffee and potato products were largest contributors to intake. The multivariate-adjusted relative risk of prostate cancer was 1.02 (95% confidence interval: 0.92-1.13) for the highest versus lowest quintile of acrylamide intake (p-value for trend = 0.90). Results were similar when restricted to never smokers and to men who had prostate-specific antigen (PSA) tests. There was no significant association for dietary acrylamide and risk of lethal, advanced or high-grade disease, or for different latency periods ranging from 0-4 years to 12-16 years. We found no evidence that acrylamide intake, within the range of US diets, is associated with increased risk of prostate cancer. Copyright © 2011 UICC.

  8. ERBB2 Increases Metastatic Potentials Specifically in Androgen-Insensitive Prostate Cancer Cells

    PubMed Central

    Tome-Garcia, Jessica; Li, Dan; Ghazaryan, Seda; Shu, Limin; Wu, Lizhao

    2014-01-01

    Despite all the blood-based biomarkers used to monitor prostate cancer patients, prostate cancer remains as the second common cause of cancer mortality in men in the United States. This is largely due to a lack of understanding of the molecular pathways that are responsible for the aggressive forms of prostate cancers, the castrate-resistant prostate cancer and the metastatic prostate cancer. Cell signaling pathways activated by the ERBB2 oncogene or the RAS oncogene are frequently found to be altered in metastatic prostate cancers. To evaluate and define the role of the ERBB2/RAS pathway in prostate cancer metastasis, we have evaluated the impact of ERBB2- or RAS-overexpression on the metastatic potentials for four prostate cancer cell lines derived from tumors with different androgen sensitivities. To do so, we transfected the human DU145, LnCaP, and PC3 prostate cancer cells and the murine Myc-CaP prostate cancer cells with the activated form of ERBB2 or H-RAS and assessed their metastatic potentials by three complementary assays, a wound healing assay, a transwell motility assay, and a transwell invasion assay. We showed that while overexpression of ERBB2 increased the metastatic potential of the androgen-insensitive prostate cancer cells (i.e. PC3 and DU145), it did not affect metastatic potentials of the androgen-sensitive prostate cancer cells (i.e. LnCaP and Myc-CaP). In contrast, overexpression of H-RAS only increased the cell motility of Myc-CaP cells, which overexpress the human c-MYC oncogene. Our data suggest that ERBB2 collaborates with androgen signaling to promote prostate cancer metastasis, and that although RAS is one of the critical downstream effectors of ERBB2, it does not phenocopy ERBB2 for its impact on the metastatic potentials of prostate cancer cell lines. PMID:24937171

  9. BPH and prostate cancer risk.

    PubMed

    Miah, Saiful; Catto, James

    2014-04-01

    With the exclusion of non-melanomatous skin malignancy, prostate cancer (PCa) is the second most prevalent cancer in men globally. It has been reported that the majority of men will develop benign prostatic hyperplasia (BPH) by the time they reach their 60s. Together, these prostatic diseases have a significant morbidity and mortality affecting over a billion men throughout the world. The risk of developing prostate cancer of men suffering BPH is one that has resulted in a healthy debate amongst the urological community. Here, we try to address this conundrum with clinical and basic science evidence. Data from an online search and contemporary data presented at international urological congresses was reviewed. BPH and PCa can be linked together at a molecular and cellular level on genetic, hormonal, and inflammatory platforms suggesting that these prostatic diseases have common pathophysiological driving factors. Epidemiological studies are weighted towards the presence of BPH having a greater risk for a man to develop PCa in his lifetime; however, a conclusion of causality cannot be confidently stated. The future workload healthcare practitioners will face regarding BPH, and PCa will substantially increase. Further basic science and large epidemiological studies using a global cohort of men are required prior to the urological community confidently counseling their patients with BPH with regards to their PCa risk.

  10. Prostate cancer in Germany among migrants from the Former Soviet Union

    PubMed Central

    Winkler, Volker; Holleczek, Bernd; Stegmaier, Christa; Becher, Heiko

    2012-01-01

    Background In Germany, prostate cancer is the leading cause of cancer and the third leading cause of death from cancer in males. We investigate prostate cancer in Gernmany among migrants from the Former Soviet Union (FSU) and compare them to indigenous German population with regard to prostate cancer incidence, mortality and longitudinal effects. Methods Data were obtained from two migrant cohorts residing in the federal states of North Rhine Westphalia (n=34,393) and Saarland (n=18,619). Vital status was ascertained through local population registries. Causes of death were obtained from the federal statistical office or from local health authorities. Cancer incidence of the Saarland cohort was derived from the Saarland Cancer Registry using record linkage. Results From 1990 to 2005 we observed 3360 deaths of which 28 were due to prostate cancer. In the Saarland cohort 35 men were diagnosed with prostate cancer during the respective period. Migrants had lower prostate cancer incidence (SIR 0.74 (95% CI: 0.52–1.03)) and mortality (SMR 0.57 (95% CI: 0.38–0.83)) compared to the German population. Multivariate analysis showed a strong age effect on incidence meaning young migrants (below age 60) were diagnosed significantly more often with prostate cancer compared to Germans of the same age. However, mortality did not show any effects. Discussion Lower prostate cancer mortality and incidence among migrants may reflect an ongoing situation in the FSU. Additionally, longitudinal analysis did not reveal convergence of migrant prostate cancer to German rates as expected from lifestyle driven cancer sites. Therefore, our results support the hypothesis of a genetic effect on prostate cancer risk. PMID:22229025

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

    PubMed

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

    2013-10-01

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

  12. P52 Activation and Enzalutamide Therapy in Prostate Cancer

    DTIC Science & Technology

    2017-10-01

    c-Myc:hnRNPA1 pathway regulates expression of androgen receptor splice variants and enzalutamide sensitivity in prostate cancer . Castration resistant... prostate cancer (CRPC) remains dependent on androgen receptor (AR) signaling. Alternative splicing of the AR to generate constitutively active... receptor splice variants and enzalutamide sensitivity in prostate cancer . • We discovered that quercetin, a naturally occurring polyphenolic compound

  13. Targeting Quiescence in Prostate Cancer

    DTIC Science & Technology

    actively dividing cancer cells causing primary tumor shrinkage, but leave behind quiescent cancer cells which may seed new, more aggressive and chemo...resistant cancers at a later date . During this first year of funding, we have successfully developed prostate cancer cell lines carrying fluorescent cell

  14. Tuberculous prostatitis: mimicking a cancer.

    PubMed

    Aziz, El Majdoub; Abdelhak, Khallouk; Hassan, Farih Moulay

    2016-01-01

    Genitourinary tuberculosis is a common type of extra-pulmonary tuberculosis . The kidneys, ureter, bladder or genital organs are usually involved. Tuberculosis of the prostate has mainly been described in immune-compromised patients. However, it can exceptionally be found as an isolated lesion in immune-competent patients. Tuberculosis of the prostate may be difficult to differentiate from carcinoma of the prostate and the chronic prostatitis when the prostate is hard and nodular on digital rectal examination and the urine is negative for tuberculosis bacilli. In many cases, a diagnosis of tuberculous prostatitis is made by the pathologist, or the disease is found incidentally after transurethral resection. Therefore, suspicion of tuberculous prostatitis requires a confirmatory biopsy of the prostate. We report the case of 60-year-old man who presented a low urinary tract syndrome. After clinical and biological examination, and imaging, prostate cancer was highly suspected. Transrectal needle biopsy of the prostate was performed and histological examination showed tuberculosis lesions.

  15. Exploring prostate cancer literacy and family cancer awareness in college students: getting ahead of the curve in cancer education.

    PubMed

    Campbell, Lisa C; McClain, Jasmyne

    2013-12-01

    Cancer literacy and family cancer experiences have not been widely researched from the perspective of young adults. This study examined health literacy related to prostate cancer and family cancer awareness among a sample of 146 male and female college students. Results supported conventional wisdom that males would be more knowledgeable about the anatomical location of the prostate as compared to females. More notably, across the sample participants had limited knowledge of comprehensive prostate cancer screening but were generally aware of the prostate specific antigen blood test, as well as age and diet as risk factors for prostate cancer. Emerging associations between sexual health history and prostate cancer risk were not widely known by the sample as a whole and perceived availability of prostate health education in college was low. Finally, gender differences in family communication about cancer and racial differences in the number of family members with cancer were observed, which could have implications for perpetuating existing gender and racial gaps in health literacy and cancer awareness. A lifespan approach to cancer education research is suggested to identify ways to promote lifelong learning about cancer, promote prevention behaviors and informed screening in young adulthood, and beyond and better prepare adults to face a family or personal cancer diagnosis should that occur in the future.

  16. Cohort Profile: the National Prostate Cancer Register of Sweden and Prostate Cancer data Base Sweden 2.0.

    PubMed

    Van Hemelrijck, Mieke; Wigertz, Annette; Sandin, Fredrik; Garmo, Hans; Hellström, Karin; Fransson, Per; Widmark, Anders; Lambe, Mats; Adolfsson, Jan; Varenhorst, Eberhard; Johansson, Jan-Erik; Stattin, Pär

    2013-08-01

    In 1987, the first Regional Prostate Cancer Register was set up in the South-East health-care region of Sweden. Other health-care regions joined and since 1998 virtually all prostate cancer (PCa) cases are registered in the National Prostate Cancer Register (NPCR) of Sweden to provide data for quality assurance, bench marking and clinical research. NPCR includes data on tumour stage, Gleason score, serum level of prostate-specific antigen (PSA) and primary treatment. In 2008, the NPCR was linked to a number of other population-based registers by use of the personal identity number. This database named Prostate Cancer data Base Sweden (PCBaSe) has now been extended with more cases, longer follow-up and a selection of two control series of men free of PCa at the time of sampling, as well as information on brothers of men diagnosed with PCa, resulting in PCBaSe 2.0. This extension allows for studies with case-control, cohort or longitudinal case-only design on aetiological factors, pharmaceutical prescriptions and assessment of long-term outcomes. The NPCR covers >96% of all incident PCa cases registered by the Swedish Cancer Register, which has an underreporting of <3.7%. The NPCR is used to assess trends in incidence, treatment and outcome of men with PCa. Since the national registers linked to PCBaSe are complete, studies from PCBaSe 2.0 are truly population based.

  17. Prostatic specific antigen. From its early days until becoming a prostate cancer biomarker.

    PubMed

    Dellavedova, T

    2016-01-01

    Prostate-specific antigen (PSA) has been since the mid 80's the most commonly used biomarker for measuring current and future risk of prostate cancer, for its early detection and to measure response to treatments and detecting recurrence in all stages of the disease. PSA's early development came along with progress in the field of immunology, which allowed detection and study of antigens from different tissues and fluids when injecting them into rabbits to promote immune response. Rubin Flocks in 1960 was the first to investigate and discover prostate-specific antigens in benign and malignant tissue. Some years later, Hara, a Japanese forensic investigator, found 'gamma seminoprotein', that he used to detect human semen in rape cases. However, his work published in Japanese did not reach the Englishspeaking scientific community. In 1970 Ablin discovered both in prostatic fluid and tissue what he called "prostate-specific antigen", but he didn't characterize or describe it. Investigators Li and Beling, and Sensabaugh, approached the current PSA, but they were limited by available technology at that time. Dr T Ming Chu led a research team on prostate cancer in New York, USA and published their results in 1979. He finally received the patent for the discovery of "human purified prostate antigen" in 1984. Due to this work, the Food and Drug Administration (FDA), in USA, approved the use of PSA for monitoring recurrence after treatment. It was later known that PSA was not prostate-specific since it was produced in other tissues and fluids, but it was recognized that it was human species-specific. Works by Papsidero and Stamey showed new indications and utilities for PSA, but it was Catalona who first used it as a marker for prostate cancer in 1991. Thanks to these advances FDA authorized in 1994 the clinical use of PSA for early detection of prostate cancer.

  18. Circadian Genes and Risk for Prostate Cancer

    DTIC Science & Technology

    2011-09-01

    placebo-controlled clinical trial to determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer. In Year 3 of the...risk. Our study is nested within the Prostate Cancer Prevention Trial (PCPT), a randomized placebo-controlled clinical trial to determine if finasteride

  19. Prostate Cancer Screening: Should You Get a PSA Test?

    MedlinePlus

    ... Mayo Clinic Staff Cancer screening tests — including the prostate-specific antigen (PSA) test to look for signs of prostate ... of harm to the person undergoing the testing. Prostate-specific antigen (PSA) is a protein produced by both cancerous ( ...

  20. Body mass index in relation to serum prostate-specific antigen levels and prostate cancer risk.

    PubMed

    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 < 30, 30 < 35 and ≥35 kg/m(2), respectively, compared to the reference (18.5 < 25 kg/m(2)). No statistically significant associations were seen between BMI and 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.

  1. A case report of prostate cancer metastasis to the stomach resembling undifferentiated-type early gastric cancer.

    PubMed

    Inagaki, Chiaki; Suzuki, Takuto; Kitagawa, Yoshiyasu; Hara, Taro; Yamaguchi, Taketo

    2017-08-07

    Occurrence of metastatic cancer to the stomach is rare, particularly in patients with prostate cancer. Gastric metastasis generally presents as a solitary and submucosal lesion with a central depression. We describe a case of gastric metastasis arising from prostate cancer, which is almost indistinguishable from the undifferentiated-type gastric cancer. A definitive diagnosis was not made until endoscopic resection. On performing both conventional and magnifying endoscopies, the lesion appeared to be slightly depressed and discolored area and it could not be distinguished from undifferentiated early gastric cancer. Biopsy from the lesion was negative for immunohistochemical staining of prostate-specific antigen, a sensitive and specific marker for prostate cancer. Thus, false initial diagnosis of an early primary gastric cancer was made and endoscopic submucosal dissection was performed. Pathological findings from the resected specimen aroused suspicion of a metastatic lesion. Consequently, immunostaining was performed. The lesion was positive for prostate-specific acid phosphatase and negative for prostate-specific antigen, cytokeratin 7, and cytokeratin 20. Accordingly, the final diagnosis was a metastatic gastric lesion originating from prostate cancer. In this patient, the definitive diagnosis as a metastatic lesion was difficult due to its unusual endoscopic appearance and the negative stain for prostate-specific antigen. We postulate that both of these are consequences of hormonal therapy against prostate cancer.

  2. The Prostate Cancer Biorepository Network (PCBN)

    DTIC Science & Technology

    2016-10-01

    site includes blood (serum, plasma, and buffy coat), prostatectomy tissues (frozen), biopsies and metastatic tissue from rapid autopsies (paraffin...embedded material and tissue microarrays (TMAs)), prostate cancer patient derived xenografts (PDX) and derived specimens (DNA and RNA) from prostate...Genitourinary Cancer Biorepository set up a rapid autopsy program to provide access to metastatic tissue and create patient derived xenograft (PDX

  3. Barriers and facilitators of prostate cancer screening among Filipino men in Hawaii.

    PubMed

    Conde, Francisco A; Landier, Wendy; Ishida, Dianne; Bell, Rose; Cuaresma, Charlene F; Misola, Jane

    2011-03-01

    To examine perceptions, attitudes, and beliefs regarding barriers and facilitators to prostate cancer screening, and to identify potential interventional strategies to promote prostate cancer screening among Filipino men in Hawaii. Exploratory, qualitative. Community-based settings in Hawaii. 20 Filipino men age 40 years or older. Focus group discussions were tape recorded and transcribed, and content analysis was performed for emergent themes. Perceptions regarding prostate cancer, barriers and facilitators to prostate cancer screening, and culturally relevant interventional strategies. Perceptions of prostate cancer included fatalism, hopelessness, and dread. Misconceptions regarding causes of prostate cancer, such as frequency of sexual activity, were identified. Barriers to prostate cancer screening included lack of awareness of the need for screening, reticence to seek health care when feeling well, fear of cancer diagnosis, financial issues, time constraints, and embarrassment. Presence of urinary symptoms, personal experience with family or friends who had cancer, and receiving recommendations from a healthcare provider regarding screening were facilitators for screening. Potential culturally relevant interventional strategies to promote prostate cancer screening included screening recommendations from healthcare professionals and cancer survivors; radio or television commercials and newspaper articles targeting the Filipino community; informational brochures in Tagalog, Ilocano, or English; and interactive, educational forums facilitated by multilingual Filipino male healthcare professionals. Culturally relevant interventions are needed that address barriers to prostate cancer screening participation and misconceptions about causes of prostate cancer. Findings provide a foundation for future research regarding development of interventional strategies to promote prostate cancer screening among Filipino men.

  4. Prostate and Colon Cancer Screening Messages in Popular Magazines

    PubMed Central

    Katz, Mira L; Sheridan, Stacey; Pignone, Michael; Lewis, Carmen; Battle, Jamila; Gollop, Claudia; O'Malley, Michael

    2004-01-01

    OBJECTIVES To 1) compare the number of articles published about prostate, colon, and breast cancer in popular magazines during the past 2 decades, and 2) evaluate the content of in-depth prostate and colon cancer screening articles identified from 1996 to 2001. DESIGN We used a searchable database to identify the number of prostate, colon, and breast cancer articles published in three magazines with the highest circulation from six categories. In addition, we performed a systematic review on the in-depth (≥2 pages) articles on prostate and colon cancer screening that appeared from 1996 through 2001. RESULTS Although the number of magazine articles on prostate and colon cancer published in the 1990s increased compared to the 1980s, the number of articles is approximately one third of breast cancer articles. There were 36 in-depth articles from 1996 to 2001 in which prostate or colon cancer screening were mentioned. Over 90% of the articles recommended screening. However, of those articles, only 76% (25/33; 95% confidence interval [CI], 58% to 89%) cited screening guidelines. The benefits of screening were mentioned in 89% (32/36; 95% CI, 74% to 97%) but the harms were only found in 58% (21/36; 95% CI, 41% to 75%). Only 28% (10/36; 95% CI, 14% to 45%) of the articles provided all the necessary information needed for the reader to make an informed decision. CONCLUSIONS In-depth articles about prostate and colon cancer in popular magazines do not appear as frequently as articles about breast cancer. The available articles on prostate and colon cancer screening often do not provide the information necessary for the reader to make an informed decision about screening. PMID:15242469

  5. Targeting Stromal Recruitment by Prostate Cancer Cells

    DTIC Science & Technology

    2006-03-01

    Ensinger, C., Tumer , Z., Tommerup, N. et al.: Hedgehog signaling in small-cell lung cancer : frequent in vivo but a rare event in vitro. Lung Cancer , 52...W81XWH-04-1-0157 TITLE: Targeting Stromal Recruitment by Prostate Cancer Cells PRINCIPAL INVESTIGATOR: Jingxian Zhang, Ph.D...DATES COVERED (From - To) 15 Feb 2004 – 14 Feb 2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting Stromal Recruitment by Prostate Cancer

  6. Emerging proteomics biomarkers and prostate cancer burden in Africa

    PubMed Central

    Adeola, Henry A.; Blackburn, Jonathan M.; Rebbeck, Timothy R.; Zerbini, Luiz F.

    2017-01-01

    Various biomarkers have emerged via high throughput omics-based approaches for use in diagnosis, treatment, and monitoring of prostate cancer. Many of these have yet to be demonstrated as having value in routine clinical practice. Moreover, there is a dearth of information on validation of these emerging prostate biomarkers within African cohorts, despite the huge burden and aggressiveness of prostate cancer in men of African descent. This review focusses of the global landmark achievements in prostate cancer proteomics biomarker discovery and the potential for clinical implementation of these biomarkers in Africa. Biomarker validation processes at the preclinical, translational and clinical research level are discussed here, as are the challenges and prospects for the evaluation and use of novel proteomic prostate cancer biomarkers. PMID:28388542

  7. Emerging proteomics biomarkers and prostate cancer burden in Africa.

    PubMed

    Adeola, Henry A; Blackburn, Jonathan M; Rebbeck, Timothy R; Zerbini, Luiz F

    2017-06-06

    Various biomarkers have emerged via high throughput omics-based approaches for use in diagnosis, treatment, and monitoring of prostate cancer. Many of these have yet to be demonstrated as having value in routine clinical practice. Moreover, there is a dearth of information on validation of these emerging prostate biomarkers within African cohorts, despite the huge burden and aggressiveness of prostate cancer in men of African descent. This review focusses of the global landmark achievements in prostate cancer proteomics biomarker discovery and the potential for clinical implementation of these biomarkers in Africa. Biomarker validation processes at the preclinical, translational and clinical research level are discussed here, as are the challenges and prospects for the evaluation and use of novel proteomic prostate cancer biomarkers.

  8. About the Prostate and Urologic Cancer Research Group | Division of Cancer Prevention

    Cancer.gov

    The Prostate and Urologic Cancer Research Group conducts and supports research on prostate and bladder cancers, and new approaches to clinical prevention studies including cancer immunoprevention. The group develops, implements and monitors research efforts in chemoprevention, nutrition, genetic, and immunologic interventions, screening, early detection and other prevention

  9. Saw palmetto supplement use and prostate cancer risk.

    PubMed

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

    2006-01-01

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

  10. Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement.

    PubMed

    Grossman, David C; Curry, Susan J; Owens, Douglas K; Bibbins-Domingo, Kirsten; Caughey, Aaron B; Davidson, Karina W; Doubeni, Chyke A; Ebell, Mark; Epling, John W; Kemper, Alex R; Krist, Alex H; Kubik, Martha; Landefeld, C Seth; Mangione, Carol M; Silverstein, Michael; Simon, Melissa A; Siu, Albert L; Tseng, Chien-Wen

    2018-05-08

    In the United States, the lifetime risk of being diagnosed with prostate cancer is approximately 13%, and the lifetime risk of dying of prostate cancer is 2.5%. The median age of death from prostate cancer is 80 years. Many men with prostate cancer never experience symptoms and, without screening, would never know they have the disease. African American men and men with a family history of prostate cancer have an increased risk of prostate cancer compared with other men. To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on prostate-specific antigen (PSA)-based screening for prostate cancer. The USPSTF reviewed the evidence on the benefits and harms of PSA-based screening for prostate cancer and subsequent treatment of screen-detected prostate cancer. The USPSTF also commissioned a review of existing decision analysis models and the overdiagnosis rate of PSA-based screening. The reviews also examined the benefits and harms of PSA-based screening in patient subpopulations at higher risk of prostate cancer, including older men, African American men, and men with a family history of prostate cancer. Adequate evidence from randomized clinical trials shows that PSA-based screening programs in men aged 55 to 69 years may prevent approximately 1.3 deaths from prostate cancer over approximately 13 years per 1000 men screened. Screening programs may also prevent approximately 3 cases of metastatic prostate cancer per 1000 men screened. Potential harms of screening include frequent false-positive results and psychological harms. Harms of prostate cancer treatment include erectile dysfunction, urinary incontinence, and bowel symptoms. About 1 in 5 men who undergo radical prostatectomy develop long-term urinary incontinence, and 2 in 3 men will experience long-term erectile dysfunction. Adequate evidence shows that the harms of screening in men older than 70 years are at least moderate and greater than in younger men because of increased risk of false

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

    PubMed

    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.

  12. PRECISION MANAGEMENT OF LOCALIZED PROSTATE CANCER

    PubMed Central

    VanderWeele, David J.; Turkbey, Baris; Sowalsky, Adam G.

    2017-01-01

    Introduction The vast majority of men who are diagnosed with prostate cancer die of other causes, highlighting the importance of determining which patient has a risk of death from prostate cancer. Precision management of prostate cancer patients includes distinguishing which men have potentially lethal disease and employing strategies for determining which treatment modality appropriately balances the desire to achieve a durable response while preventing unnecessary overtreatment. Areas covered In this review, we highlight precision approaches to risk assessment and a context for the precision-guided application of definitive therapy. We focus on three dilemmas relevant to the diagnosis of localized prostate cancer: screening, the decision to treat, and postoperative management. Expert commentary In the last five years, numerous precision tools have emerged with potential benefit to the patient. However, to achieve optimal outcome, the decision to employ one or more of these tests must be considered in the context of prevailing conventional factors. Moreover, performance and interpretation of a molecular or imaging precision test remains practitioner-dependent. The next five years will witness increased marriage of molecular and imaging biomarkers for improved multi-modal diagnosis and discrimination of disease that is aggressive versus truly indolent. PMID:28133630

  13. Prostate cancer burden in Central and South America.

    PubMed

    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.

  14. Breast and Prostate Cancer Cohort Consortium (BPC3)

    Cancer.gov

    Breast and Prostate Cancer Cohort Consortium collaborates with three genomic facilities, epidemiologists, population geneticists, and biostatisticians from multiple institutions to study hormone-related gene variants and environmental factors in breast and prostate cancers.

  15. Age-dependent associations between androgenetic alopecia and prostate cancer risk.

    PubMed

    Muller, David C; Giles, Graham G; Sinclair, Rod; Hopper, John L; English, Dallas R; Severi, Gianluca

    2013-02-01

    Both prostate cancer and androgenetic alopecia are strongly age-related conditions that are considered to be androgen dependent, but studies of the relationship between them have yielded inconsistent results. We aimed to assess whether androgenetic alopecia at ages 20 and 40 years are associated with risk of prostate cancer. At a follow-up of the Melbourne Collaborative Cohort Study, men were asked to assess their hair pattern at ages 20 and 40 years relative to eight categories in showcards. Cases were men notified to the Victorian Cancer Registry with prostate cancer diagnosed between cohort enrollment (1990-1994) and follow-up attendance (2003-2009). Flexible parametric survival models were used to estimate age-varying HRs and predicted cumulative probabilities of prostate cancer by androgenetic alopecia categories. Of 9,448 men that attended follow-up and provided data on androgenetic alopecia, we identified 476 prostate cancer cases during a median follow-up of 11 years four months. Cumulative probability of prostate cancer was greater at all ages up to 76 years, for men with vertex versus no androgenetic alopecia at age of 40 years. At age of 76 years, the estimated probabilities converged to 0.15. Vertex androgenetic alopecia at 40 years was also associated with younger age of diagnosis for prostate cancer cases. Vertex androgenetic alopecia at age of 40 years might be a marker of increased risk of early-onset prostate cancer. If confirmed, these results suggest that the apparently conflicting findings of previous studies might be explained by failure to adequately model the age-varying nature of the association between androgenetic alopecia and prostate cancer.

  16. Prostate Cancer Symptoms

    MedlinePlus

    ... Us The Story of PCF A Legacy of Leadership About the Prostate Cancer Foundation CEO Message Why ... PCF? Support our Partners Annual Report & Financials Our Leadership Leadership Team Board Members Curing Together Patient Stories ...

  17. The politics of prostate cancer screening.

    PubMed

    Kaffenberger, Samuel D; Penson, David F

    2014-05-01

    The controversial recent recommendation by the United States Preventive Services Task Force (USPSTF) against prostate-specific antigen (PSA) screening for early-stage prostate cancer has caused much debate. Whereas USPSTF recommendations against routine screening mammography in younger women resulted in fierce public outcry and eventual alteration in the language of the recommendation, the same public and political response has not been seen with PSA screening for prostate cancer. It is of paramount importance to ensure improved efficiency and transparency of the USPSTF recommendation process, and resolution of concerns with the current USPSTF recommendation against PSA screening for all ages. Published by Elsevier Inc.

  18. The genomic complexity of primary human prostate cancer

    PubMed Central

    Berger, Michael F.; Lawrence, Michael S.; Demichelis, Francesca; Drier, Yotam; Cibulskis, Kristian; Sivachenko, Andrey Y.; Sboner, Andrea; Esgueva, Raquel; Pflueger, Dorothee; Sougnez, Carrie; Onofrio, Robert; Carter, Scott L.; Park, Kyung; Habegger, Lukas; Ambrogio, Lauren; Fennell, Timothy; Parkin, Melissa; Saksena, Gordon; Voet, Douglas; Ramos, Alex H.; Pugh, Trevor J.; Wilkinson, Jane; Fisher, Sheila; Winckler, Wendy; Mahan, Scott; Ardlie, Kristin; Baldwin, Jennifer; Simons, Jonathan W.; Kitabayashi, Naoki; MacDonald, Theresa Y.; Kantoff, Philip W.; Chin, Lynda; Gabriel, Stacey B.; Gerstein, Mark B.; Golub, Todd R.; Meyerson, Matthew; Tewari, Ashutosh; Lander, Eric S.; Getz, Gad; Rubin, Mark A.; Garraway, Levi A.

    2010-01-01

    Prostate cancer is the second most common cause of male cancer deaths in the United States. Here we present the complete sequence of seven primary prostate cancers and their paired normal counterparts. Several tumors contained complex chains of balanced rearrangements that occurred within or adjacent to known cancer genes. Rearrangement breakpoints were enriched near open chromatin, androgen receptor and ERG DNA binding sites in the setting of the ETS gene fusion TMPRSS2-ERG, but inversely correlated with these regions in tumors lacking ETS fusions. This observation suggests a link between chromatin or transcriptional regulation and the genesis of genomic aberrations. Three tumors contained rearrangements that disrupted CADM2, and four harbored events disrupting either PTEN (unbalanced events), a prostate tumor suppressor, or MAGI2 (balanced events), a PTEN interacting protein not previously implicated in prostate tumorigenesis. Thus, genomic rearrangements may arise from transcriptional or chromatin aberrancies to engage prostate tumorigenic mechanisms. PMID:21307934

  19. CYP17 inhibitors for prostate cancer therapy

    PubMed Central

    Vasaitis, Tadas S.; Bruno, Robert D.; Njar, Vincent C. O.

    2010-01-01

    Prostate cancer (PC) is now the second most prevalent cause of death in men in the USA and Europe. At present, the major treatment options include surgical or medical castration. These strategies cause ablation of the production of testosterone (T), dihydrotestosterone (DHT) and related androgens by the testes. However, because these procedures do not affect adrenal, prostate and other tissues androgen production, they are often combined with androgen receptor antagonists to block their action. Indeed, recent studies have unequivocally established that in castration-resistant prostate cancer (CRPC) many androgen-regulated genes become re-expressed and tissue androgen levels increase despite low serum levels. Clearly, inhibition of the key enzyme which catalyzes the biosynthesis of androgens from pregnane precursors, 17α-hydroxy/17,20-lyase (hereafter referred to as CYP17) could prevent androgen production from all sources. Thus, total ablation of androgen production by potent CYP17 inhibitors may provide effective treatment of prostate cancer patients. This review highlights the role of androgen biosynthesis in the progression of prostate cancer and the impact of CYP17 inhibitors, such as ketoconazole, abiraterone acetate, VN/124-1 (TOK-001) and TAK-700 in the clinic and in clinical development. PMID:21092758

  20. Multiparametric magnetic resonance imaging predicts the presence of prostate cancer in patients with negative prostate biopsy.

    PubMed

    Lista, F; Castillo, E; Gimbernat, H; Rodríguez-Barbero, J M; Panizo, J; Angulo, J C

    2015-03-01

    To assess the ability of multiparametric prostate magnetic resonance imaging (mpMRI) to detect prostate cancer in patients with prior negative transrectal prostate biopsy (TPB). mpMRI (TSE-T2-w, DWI and DCE sequences) was performed on 1.5T (Magnetom Avanto; Siemens Healthcare Solutions) in 150 patients suspicious of prostate cancer and with negative TPB. European Society of Urogenital Radiology (ESUR) criteria were used (score 1: clinically significant disease is highly unlikely to be present; score 2: clinically significant cancer is unlikely to be present; score 3: clinically significant cancer is equivocal; score 4: clinically significant cancer is likely to be present; score 5: clinically significant cancer is highly likely to be present). PSA measurement (total and free), digital rectal examination (DRE), transrectal ultrasound (TRU) and a second TPB (at least 14 cylinders) were performed in all patients. Variables were submitted for independent blind analysis. The accuracy of each test was measured. Stepwise selection model for prediction of prostate cancer in second TPB was developed. Mean age was 66.2± 5 years (51-77), mean PSA 11.3± 9.6ng/mL (0.9-75) and mean prostatic volume 82.2±42 (20-250) cc. DRE was suspicious in 11 (7.3%) patients. The mean number of cylinders per patient sampled in second TRB was 17.6±2.7(14-22). Second TRB was positive in 28 patients (18.7%). mpMRI was positive (score 3-5) in 102 (68%), test sensibility was 92.9% and the NPV was 95.8%. The risk of prostate cancer diagnosis in second TPB is modified by: PSA velocity > 0.75 (OR 1.04 [0.99-1.08]; P=0.06), free/total ratio PSA <15% (OR 0.37 [0.13-1.05]; P=0.06), each cc. of prostate volume (OR 0.98 [0.97-1]; P=0.017) and mpMRI 3-5 (OR 7.87 [1.78-34.7]; P=0.006). Multivariate analysis reveals that mpMRI (OR 7.41 [1.65-33.28]; P=0.009) and prostatic volume (OR 0.31 [0.12-0.78]; P=0.01) are independent risk predictors of prostate cancer. According to ESUR guidelines and in patients

  1. Prostate cancer region prediction using MALDI mass spectra

    NASA Astrophysics Data System (ADS)

    Vadlamudi, Ayyappa; Chuang, Shao-Hui; Sun, Xiaoyan; Cazares, Lisa; Nyalwidhe, Julius; Troyer, Dean; Semmes, O. John; Li, Jiang; McKenzie, Frederic D.

    2010-03-01

    For the early detection of prostate cancer, the analysis of the Prostate-specific antigen (PSA) in serum is currently the most popular approach. However, previous studies show that 15% of men have prostate cancer even their PSA concentrations are low. MALDI Mass Spectrometry (MS) proves to be a better technology to discover molecular tools for early cancer detection. The molecular tools or peptides are termed as biomarkers. Using MALDI MS data from prostate tissue samples, prostate cancer biomarkers can be identified by searching for molecular or molecular combination that can differentiate cancer tissue regions from normal ones. Cancer tissue regions are usually identified by pathologists after examining H&E stained histological microscopy images. Unfortunately, histopathological examination is currently done on an adjacent slice because the H&E staining process will change tissue's protein structure and it will derogate MALDI analysis if the same tissue is used, while the MALDI imaging process will destroy the tissue slice so that it is no longer available for histopathological exam. For this reason, only the most confident cancer region resulting from the histopathological examination on an adjacent slice will be used to guide the biomarker identification. It is obvious that a better cancer boundary delimitation on the MALDI imaging slice would be beneficial. In this paper, we proposed methods to predict the true cancer boundary, using the MALDI MS data, from the most confident cancer region given by pathologists on an adjacent slice.

  2. EDB Fibronectin Specific Peptide for Prostate Cancer Targeting.

    PubMed

    Han, Zheng; Zhou, Zhuxian; Shi, Xiaoyue; Wang, Junpeng; Wu, Xiaohui; Sun, Da; Chen, Yinghua; Zhu, Hui; Magi-Galluzzi, Cristina; Lu, Zheng-Rong

    2015-05-20

    Extradomain-B fibronectin (EDB-FN), one of the oncofetal fibronectin (onfFN) isoforms, is a high-molecular-weight glycoprotein that mediates cell adhesion and migration. The expression of EDB-FN is associated with a number of cancer-related biological processes such as tumorigenesis, angiogenesis, and epithelial-to-mesenchymal transition (EMT). Here, we report the development of a small peptide specific to EDB-FN for targeting prostate cancer. A cyclic nonapeptide, CTVRTSADC (ZD2), was identified using peptide phage display. A ZD2-Cy5 conjugate was synthesized to accomplish molecular imaging of prostate cancer in vitro and in vivo. ZD2-Cy5 demonstrated effective binding to up-regulated EDB-FN secreted by TGF-β-induced PC3 cancer cells following EMT. Following intravenous injections, the targeted fluorescent probe specifically bound to and delineated PC3-GFP prostate tumors in nude mice bearing the tumor xenografts. ZD2-Cy5 also showed stronger binding to human prostate tumor specimens with a higher Gleason score (GS9) compared to those with a lower score (GS 7), with no binding in benign prostatic hyperplasia (BPH). Thus, the ZD2 peptide is a promising strategy for molecular imaging and targeted therapy of prostate cancer.

  3. Prostate Cancer Screening: MedlinePlus Health Topic

    MedlinePlus

    ... unusual. Another test is the prostate-specific antigen (PSA) blood test. Your PSA level may be high if you have prostate ... Research) Prostate Cancer Screening: Should You Get a PSA Test? (Mayo Foundation for Medical Education and Research) ...

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

    PubMed

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

    2016-07-01

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

  5. What Prostate Cancer Survivors Need to Know about Osteoporosis

    MedlinePlus

    ... What Prostate Cancer Survivors Need to Know About Osteoporosis The Impact of Prostate Cancer The National Cancer ... Management Strategies Resources For Your Information Facts About Osteoporosis Osteoporosis is a condition in which bones become ...

  6. Combining lymphovascular invasion with reactive stromal grade predicts prostate cancer mortality.

    PubMed

    Saeter, Thorstein; Vlatkovic, Ljiljana; Waaler, Gudmund; Servoll, Einar; Nesland, Jahn M; Axcrona, Karol; Axcrona, Ulrika

    2016-09-01

    Previous studies suggest that lymphovascular invasion (LVI) has a weak and variable effect on prognosis. It is uncertain whether LVI, determined by diagnostic prostate biopsy, predicts prostate cancer death. Data from experimental studies have indicated that carcinoma-associated fibroblasts in the reactive stroma could promote LVI and progression to metastasis. Thus, combining LVI with reactive stromal grade may identify prostate cancer patients at high risk of an unfavorable outcome. The purpose of the present study was to examine if LVI, determined by diagnostic biopsy, alone and in combination with reactive stromal grade could predict prostate cancer death. This population-based study included 283 patients with prostate cancer diagnosed by needle biopsy in Aust-Agder County (Norway) from 1991 to 1999. Clinical data were obtained by medical charts review. Two uropathologists evaluated LVI and reactive stromal grade. The endpoint was prostate cancer death. Patients with LVI had marginally higher risk of prostate cancer death compared to patients without LVI (hazard ratio: 1.8, P-value = 0.04). LVI had a stronger effect on prostate cancer death risk when a high reactive stromal grade was present (hazard ratio: 16.0, P-value <0.001). Therefore, patients with concomitant LVI and high reactive stromal grade were at particularly high risk for prostate cancer death. Evaluating LVI together with reactive stromal grade on diagnostic biopsies could be used to identify patients at high risk of death from prostate cancer. Prostate 76:1088-1094, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. [Treatment for locally advanced prostate cancer: value of surgery].

    PubMed

    Azuma, Haruhito; Katsuoka, Yoji

    2006-06-01

    Surgical therapy is not only a therapeutic method but also an important procedure to provide useful information in determining a postoperative treatment strategy. Compared with postoperative cancer staging based on specimens obtained during surgery, more than 30% of cancers were inaccurately staged preoperatively, even when a current advanced diagnostic imaging technique was used. Compared with postoperative histological 30-40% of cancer staging were inaccurately staged based on a preoperative biopsy. These misstaging cases pose a significantly important problem. Approximately 15% and 30% of clinical stage C prostate cancers have been rated as pT2 and pN(+), respectively. Patients with pT3 prostate cancer who underwent radical prostatectomy had 5-year and 10-year overall survival rates of 82% and 67%, respectively, which were comparable to those in patients with pT2 prostate cancer (82% and 67%, respectively). However, patients with prostate cancer rated as pT4 and pN(+) had very poor outcomes with 5-year overall survival rates of 42.4% and 32.6%, respectively. Therefore, even in patients with stage C prostate cancer, surgical therapy should be recommended if no infiltration of adjacent tissue has been noted and the operation is applicable; and an optimal postoperative therapeutic strategy should be selected based on the accurate pathological staging and histological grading using postoperative pathological specimens. Such approaches will prevent unnecessary hormone therapy in patients with pT2 prostate cancer and prevent missing optimal timing for radical cure, as well as allowing appropriate therapy to be selected for patients with pT4 and pN(+) prostate cancer, for whom prognosis may be poor.

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

    PubMed Central

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

    2017-01-01

    Objectives 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. Design Cohort study comparing night and day working twins with respect to incident prostate cancer in 12 322 men. Setting Individuals in the Swedish Twin Registry. Participants 12 322 male twins. Outcome measures Prostate cancer diagnoses obtained from the Swedish Cancer Registry with a follow-up time of 12 years, with a total number of cases=454. Results 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. Conclusions The results, together with previous studies, suggest that night work does not seem to constitute a risk factor for prostate cancer. PMID:28600375

  9. Recent Advances in Prostate Cancer Treatment and Drug Discovery.

    PubMed

    Nevedomskaya, Ekaterina; Baumgart, Simon J; Haendler, Bernard

    2018-05-04

    Novel drugs, drug sequences and combinations have improved the outcome of prostate cancer in recent years. The latest approvals include abiraterone acetate, enzalutamide and apalutamide which target androgen receptor (AR) signaling, radium-223 dichloride for reduction of bone metastases, sipuleucel-T immunotherapy and taxane-based chemotherapy. Adding abiraterone acetate to androgen deprivation therapy (ADT) in order to achieve complete androgen blockade has proven highly beneficial for treatment of locally advanced prostate cancer and metastatic hormone-sensitive prostate cancer (mHSPC). Also, ADT together with docetaxel treatment showed significant benefit in mHSPC. Ongoing clinical trials for different subgroups of prostate cancer patients include the evaluation of the second-generation AR antagonists enzalutamide, apalutamide and darolutamide, of inhibitors of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway, of inhibitors of DNA damage response, of targeted alpha therapy and of prostate-specific membrane antigen (PSMA) targeting approaches. Advanced clinical studies with immune checkpoint inhibitors have shown limited benefits in prostate cancer and more trials are needed to demonstrate efficacy. The identification of improved, personalized treatments will be much supported by the major progress recently made in the molecular characterization of early- and late-stage prostate cancer using “omics” technologies. This has already led to novel classifications of prostate tumors based on gene expression profiles and mutation status, and should greatly help in the choice of novel targeted therapies best tailored to the needs of patients.

  10. Progesterone receptor in the prostate: A potential suppressor for benign prostatic hyperplasia and prostate cancer.

    PubMed

    Chen, RuiQi; Yu, Yue; Dong, Xuesen

    2017-02-01

    Advanced prostate cancer undergoing androgen receptor pathway inhibition (ARPI) eventually progresses to castrate-resistant prostate cancer (CRPC), suggesting that (i) androgen receptor (AR) blockage is incomplete, and (ii) there are other critical molecular pathways contributing to prostate cancer (PCa) progression. Although most PCa occurs in the epithelium, prostate stroma is increasingly believed to play a crucial role in promoting tumorigenesis and facilitating tumor progression. In the stroma, sex steroid hormone receptors such as AR and estrogen receptor-α are implicated to have important functions, whereas the progesterone receptor (PR) remains largely under-investigated despite the high sequence and structural similarities between PR and AR. Stromal progesterone/PR signaling may play a critical role in PCa development and progression because not only progesterone is a critical precursor for de novo androgen steroidogenesis and an activator of mutant androgen receptors, but also PR functions in a ligand-independent manner in various important pathways. In fact, recent progress in our understanding of stromal PR function suggests that this receptor may exert an inhibitory effect on benign prostatic hyperplasia (BPH), reactive stroma development, and PCa progression. These early findings of stromal PR warrant further investigations as this receptor could be a potential biomarker and therapeutic target in PCa management. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Activation of β-catenin signaling in androgen receptor-negative prostate cancer cells.

    PubMed

    Wan, Xinhai; Liu, Jie; Lu, Jing-Fang; Tzelepi, Vassiliki; Yang, Jun; Starbuck, Michael W; Diao, Lixia; Wang, Jing; Efstathiou, Eleni; Vazquez, Elba S; Troncoso, Patricia; Maity, Sankar N; Navone, Nora M

    2012-02-01

    To study Wnt/β-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the β-catenin-androgen receptor (AR) interaction. We carried out β-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of β-catenin-mediated transcription), and sequenced the β-catenin gene in MDA prostate cancer 118a, MDA prostate cancer 118b, MDA prostate cancer 2b, and PC-3 prostate cancer cells. We knocked down β-catenin in AR-negative MDA prostate cancer 118b cells and carried out comparative gene-array analysis. We also immunohistochemically analyzed β-catenin and AR in 27 bone metastases of human CRPCs. β-Catenin nuclear accumulation and TOP-flash reporter activity were high in MDA prostate cancer 118b but not in MDA prostate cancer 2b or PC-3 cells. MDA prostate cancer 118a and MDA prostate cancer 118b cells carry a mutated β-catenin at codon 32 (D32G). Ten genes were expressed differently (false discovery rate, 0.05) in MDA prostate cancer 118b cells with downregulated β-catenin. One such gene, hyaluronan synthase 2 (HAS2), synthesizes hyaluronan, a core component of the extracellular matrix. We confirmed HAS2 upregulation in PC-3 cells transfected with D32G-mutant β-catenin. Finally, we found nuclear localization of β-catenin in 10 of 27 human tissue specimens; this localization was inversely associated with AR expression (P = 0.056, Fisher's exact test), suggesting that reduced AR expression enables Wnt/β-catenin signaling. We identified a previously unknown downstream target of β-catenin, HAS2, in prostate cancer, and found that high β-catenin nuclear localization and low or no AR expression may define a subpopulation of men with bone metastatic prostate cancer. These findings may guide physicians in managing these patients.

  12. microRNA in Prostate Cancer Racial Disparities and Aggressiveness

    DTIC Science & Technology

    2015-10-01

    1 AWARD NUMBER: W81XWH-13-1-0477 TITLE: microRNA in Prostate Cancer Racial Disparities and Aggressiveness PRINCIPAL INVESTIGATOR: Cathryn...microRNA in Prostate Cancer Racial Disparities and Aggressiveness 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0477 5c. PROGRAM ELEMENT NUMBER...final analyses. 15. SUBJECT TERMS prostate cancer, microRNA, racial disparities, African American, genetic polymorphisms, biochemical recurrence

  13. Active Sonic Hedgehog Signaling between Androgen Independent Human Prostate Cancer Cells and Normal/Benign but Not Cancer-Associated Prostate Stromal Cells

    PubMed Central

    Shigemura, Katsumi; Huang, Wen-Chin; Li, Xiangyan; Zhau, Haiyen E.; Zhu, Guodong; Gotoh, Akinobu; Fujisawa, Masato; Xie, Jingwu; Marshall, Fray F.; Chung, Leland W. K.

    2012-01-01

    BACKGROUND Sonic hedgehog (Shh) signaling plays a pivotal role in stromal-epithelial interaction during normal development but its role in tumor-stromal interaction during carcinogenic progression is less well defined. Since hormone refractory prostate cancer with bone metastasis is difficult to treat, it is crucial to investigate how androgen independent (AI) human prostate cancer cells communicate with their associated stroma. METHODS Shh and its target transcription factor, Gli1 mRNA, were assessed by RT-PCR and/or quantitative RT-PCR in co-cultured cell recombinants comprised of AI C4-2 either with NPF (prostate fibroblasts from normal/benign prostate gland) or CPF cancer-associated stromal fibroblasts) under Shh/cyclopamine (a hedgehog signaling inhibitor) treatment. Human bone marrow stromal (HS27A) cells were used as controls. In vivo investigation was performed by checking serum PSA and immunohistochemical staining for the apoptosis-associated M30 gene in mice bearing chimeric C4-2/NPF tumors. RESULTS CONCLUSIONS Based on co-culture and chimeric tumor models, active Shh-mediated signaling was demonstrated between AI prostate cancer and NPF in a paracrine- and tumor progression-dependent manner. Our study suggests that drugs like cyclopamine that interfere with Shh signaling could be beneficial in preventing AI progression in prostate cancer cells. PMID:21520153

  14. Co-Targeting Prostate Cancer Epithelium and Bone Stroma by Human Osteonectin-Promoter-Mediated Suicide Gene Therapy Effectively Inhibits Androgen-Independent Prostate Cancer Growth.

    PubMed

    Sung, Shian-Ying; Chang, Junn-Liang; Chen, Kuan-Chou; Yeh, Shauh-Der; Liu, Yun-Ru; Su, Yen-Hao; Hsueh, Chia-Yen; Chung, Leland W K; Hsieh, Chia-Ling

    2016-01-01

    Stromal-epithelial interaction has been shown to promote local tumor growth and distant metastasis. We sought to create a promising gene therapy approach that co-targets cancer and its supporting stromal cells for combating castration-resistant prostate tumors. Herein, we demonstrated that human osteonectin is overexpressed in the prostate cancer epithelium and tumor stroma in comparison with their normal counterpart. We designed a novel human osteonectin promoter (hON-522E) containing positive transcriptional regulatory elements identified in both the promoter and exon 1 region of the human osteonectin gene. In vitro reporter assays revealed that the hON-522E promoter is highly active in androgen receptor negative and metastatic prostate cancer and bone stromal cells compared to androgen receptor-positive prostate cancer cells. Moreover, in vivo prostate-tumor-promoting activity of the hON-522E promoter was confirmed by intravenous administration of an adenoviral vector containing the hON-522E promoter-driven luciferase gene (Ad-522E-Luc) into mice bearing orthotopic human prostate tumor xenografts. In addition, an adenoviral vector with the hON-522E-promoter-driven herpes simplex virus thymidine kinase gene (Ad-522E-TK) was highly effective against the growth of androgen-independent human prostate cancer PC3M and bone stromal cell line in vitro and in pre-established PC3M tumors in vivo upon addition of the prodrug ganciclovir. Because of the heterogeneity of human prostate tumors, hON-522E promoter-mediated gene therapy has the potential for the treatment of hormone refractory and bone metastatic prostate cancers.

  15. Targeted Elimination of PCDH-PC Expressing Prostate Cancer Cells for Control of Hormone-Resistant Prostate Cancer

    DTIC Science & Technology

    2008-11-01

    or antisense oligonucleotides ( ASOs ) might be useful in preventing the development of castration- recurrent prostate cancer in prostate cancer...patients. To this end, we have created functional shRNA vectors and ASOs capable of suppressing PCDH-PC expression and we have also created a monoclonal...electrophoresed on an SDS-PAGE gel and blotted onto a filter. The filter was probed with an anti-myc antibody. The levels of myc-tagged PCDH-PC protein

  16. Targeted Elimination of PCDH-PC Expressing Prostate Cancer Cells for Control of Hormone-Resistant Prostate Cancer

    DTIC Science & Technology

    2009-11-01

    expression knockout by shRNAs or antisense oligonucleotides ( ASOs ) might be useful in preventing the development of castration-recurrent prostate...cancer in prostate cancer patients. To this end, we have created functional shRNA vectors and ASOs capable of suppressing PCDH-PC expression and we have...containing PCDH-PC cDNA. Cell extracts were prepared 48 hrs after co-transfection and were electrophoresed on an SDS-PAGE gel and blotted onto a

  17. Estrogen receptor beta in prostate cancer: friend or foe?

    PubMed

    Nelson, Adam W; Tilley, Wayne D; Neal, David E; Carroll, Jason S

    2014-08-01

    Prostate cancer is the commonest, non-cutaneous cancer in men. At present, there is no cure for the advanced, castration-resistant form of the disease. Estrogen has been shown to be important in prostate carcinogenesis, with evidence resulting from epidemiological, cancer cell line, human tissue and animal studies. The prostate expresses both estrogen receptor alpha (ERA) and estrogen receptor beta (ERB). Most evidence suggests that ERA mediates the harmful effects of estrogen in the prostate, whereas ERB is tumour suppressive, but trials of ERB-selective agents have not translated into improved clinical outcomes. The role of ERB in the prostate remains unclear and there is increasing evidence that isoforms of ERB may be oncogenic. Detailed study of ERB and ERB isoforms in the prostate is required to establish their cell-specific roles, in order to determine if therapies can be directed towards ERB-dependent pathways. In this review, we summarise evidence on the role of ERB in prostate cancer and highlight areas for future research. © 2014 Society for Endocrinology.

  18. Synchronous Detection of Male Breast Cancer and Prostatic Cancer in a Patient With Suspected Prostatic Carcinoma on 68Ga-PSMA PET/CT Imaging.

    PubMed

    Kumar, Rajender; Mittal, Bhagwant Rai; Bhattacharya, Anish; Singh, Harmandeep; Singh, Shrawan Kumar

    2018-06-01

    The male breast cancer is very less common as compared with the female breast cancer. We report a case of 64-year-old man who presented with the history of lower urinary tract symptoms. The digital rectal examination revealed hard and nodular prostate, and serum prostate-specific antigen level was 23.4 ng/mL. Ga-labeled prostate-specific membrane antigen PET/CT revealed prostate-specific membrane antigen-expressing lesions in the prostate, axillary tail of the right breast, and axillary lymph nodes. Histology from prostate revealed prostate carcinoma, whereas fine-needle aspiration from the breast revealed invasive ductal carcinoma of the breast.

  19. Association Between Cd Exposure and Risk of Prostate Cancer

    PubMed Central

    Ju-Kun, Song; Yuan, Dong-Bo; Rao, Hao-Fu; Chen, Tian-Fei; Luan, Bo-Shi; Xu, Xiao-Ming; Jiang, Fu-Neng; Zhong, Wei-De; Zhu, Jian-Guo

    2016-01-01

    Abstract Several observational studies on the association between Cd exposure and risk of prostate cancer have yielded inconsistent results. To address this issue, we conducted a meta-analysis to evaluate the correlation between Cd exposure and risk of prostate cancer. Relevant studies in PubMed and Embase databases were retrieved until October 2015. We compared the highest and lowest meta-analyses to quantitatively evaluate the relationship between Cd exposure and risk of prostate cancer. Summary estimates were obtained using a random-effects model. In the general population, high Cd exposure was not associated with increased prostate cancer (OR 1.21; 95% CI 0.91–1.64), whereas the combined standardized mortality ratio of the association between Cd exposure and risk of prostate cancer was 1.66 (95% CI 1.10–2.50) in populations exposed to occupational Cd. In addition, high D-Cd intake (OR 1.07; 95% CI 0.96–1.20) and U-Cd concentration (OR 0.86; 95% CI 0.48–1.55) among the general population was not related to the increased risk of prostate cancer. In the dose analysis, the summary relative risk was 1.07 (95% CI 0.73–1.57) for each 0.5 μg/g creatinine increase in U-Cd and 1.02 (95% CI 0.99–1.06) for each 10 μg/day increase of dietary Cd intake. However, compared with nonoccupational exposure, high occupational Cd exposure may be associated with the increased risk of prostate cancer. This meta-analysis suggests high Cd exposure as a risk factor for prostate cancer in occupational rather than nonoccupational populations. However, these results should be carefully interpreted because of the significant heterogeneity among studies. Additional large-scale and high-quality prospective studies are needed to confirm the association between Cd exposure and risk of prostate cancer. PMID:26871808

  20. Current management of advanced and castration resistant prostate cancer.

    PubMed

    Gomella, Leonard G; Petrylak, Daniel P; Shayegan, Bobby

    2014-04-01

    Newer approaches to the management of advanced prostate cancer have rapidly evolved. While basic androgen deprivation remains as the first line in newly diagnosed hormone naïve metastatic prostate cancer, the agents used and strategies followed have undergone significant changes. Numerous new agents such as sipuleucel-T, abiraterone, enzalutamide, cabazitaxel and radium 223 have all been approved since 2010 to treat metastatic castration resistant prostate cancer (CRPC). New imaging techniques to detect advanced disease such as F-18 PET, 11 C-choline PET and other modalities are becoming available. The concepts of "bone health" and the management of side effects related to androgen deprivation therapy are also gaining attention as men are being treated with longer courses of androgen deprivation. Understanding the theory behind these new agents and management approaches while focusing on the practical clinical considerations are essential to improve outcomes in advanced prostate cancer. A review of the current state of the art in the management of advanced and castration resistant prostate cancer presented in this Canadian Journal of Urology International supplement was performed. Key findings are summarized and presented along with critical updates based on recent publications and meeting presentations. Key concepts identified in the management of advanced prostate cancer included the new understanding of prostate cancer based on translational discoveries, applications of various hormonally based strategies in advanced disease including traditional and recently approved agents. The use of new imaging modalities to identify metastatic disease, immunotherapy approaches and discussions of sequencing and which new agents are likely to be available in the future in the management of CRPC were identified. Bone targeted strategies are also addressed in the setting of androgen deprivation and metastatic disease. The management of men with advanced prostate cancer has

  1. [Fish intake and risk of prostate cancer].

    PubMed

    Dybkowska, Ewa; Świderski, Franciszek; Waszkiewicz-Robak, Bożena

    2014-10-17

    The aim of the study was to present the current state of knowledge concerning the relationship between the consumption of fish as materials rich in long chain polyunsaturated fatty acids (LC PUFA) omega-3, and the risk of prostate cancer. Many scientific reports confirm the health benefits from the consumption of fish and protective properties of LC PUFA omega-3 in relation to prostate cancer. However, there are reports that indicate a relationship of the high consumption of PUFA with the risk of prostate cancer. The way of processing and preservation of the fish, and other factors not included in previous studies, could have some importance in the etiology of this disease. High susceptibility of PUFA to oxidation changes and the technological fish processing (smoking, high-temperature cooking methods) contribute to the formation of many compounds, such as polycyclic aromatic hydrocarbons and heterocyclic amines - which may influence the formation of cancers - including prostate cancer. It is necessary to ensure an adequate amount of LC PUFA omega-3 in the diet through the consumption of proper quality fish and fish oils. Particular attention should be paid to the high susceptibility of PUFA to the oxidative processes, and the method of processing, preservation and storage of fish. Also pollution from the environment can significantly reduce the impact of health benefits of PUFA and fish, and even be the cause of cancers, including prostate cancer. Further research in this area should be more targeted to assess the impact of nutritional factors for the development of such tumors.

  2. Withaferin A Inhibits Prostate Carcinogenesis in a PTEN-deficient Mouse Model of Prostate Cancer.

    PubMed

    Moselhy, Jim; Suman, Suman; Alghamdi, Mohammed; Chandarasekharan, Balaji; Das, Trinath P; Houda, Alatassi; Ankem, Murali; Damodaran, Chendil

    2017-06-01

    We recently demonstrated that AKT activation plays a role in prostate cancer progression and inhibits the pro-apoptotic function of FOXO3a and Par-4. AKT inhibition and Par-4 induction suppressed prostate cancer progression in preclinical models. Here, we investigate the chemopreventive effect of the phytonutrient Withaferin A (WA) on AKT-driven prostate tumorigenesis in a Pten conditional knockout (Pten-KO) mouse model of prostate cancer. Oral WA treatment was carried out at two different doses (3 and 5 mg/kg) and compared to vehicle over 45 weeks. Oral administration of WA for 45 weeks effectively inhibited primary tumor growth in comparison to vehicle controls. Pathological analysis showed the complete absence of metastatic lesions in organs from WA-treated mice, whereas discrete metastasis to the lungs was observed in control tumors. Immunohistochemical analysis revealed the down-regulation of pAKT expression and epithelial-to-mesenchymal transition markers, such as β-catenin and N-cadherin, in WA-treated tumors in comparison to controls. This result corroborates our previous findings from both cell culture and xenograft models of prostate cancer. Our findings demonstrate that the daily administration of a phytonutrient that targets AKT activation provides a safe and effective treatment for prostate cancer in a mouse model with strong potential for translation to human disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Advanced Prostate Cancer

    MedlinePlus

    ... to learn about these types of treatments. This article is for men with metastatic and castrate-resistant ... Related Resources Urology 101 Fact Sheet UrologyHealth extra® Articles What is Advanced Prostate Cancer? Keeping Your Bones ...

  4. Targeting the relaxin hormonal pathway in prostate cancer.

    PubMed

    Neschadim, Anton; Summerlee, Alastair J S; Silvertown, Joshua D

    2015-11-15

    Targeting the androgen signalling pathway has long been the hallmark of anti-hormonal therapy for prostate cancer. However, development of androgen-independent prostate cancer is an inevitable outcome to therapies targeting this pathway, in part, owing to the shift from cancer dependence on androgen signalling for growth in favor of augmentation of other cellular pathways that provide proliferation-, survival- and angiogenesis-promoting signals. This review focuses on the role of the hormone relaxin in the development and progression of prostate cancer, prior to and after the onset of androgen independence, as well as its role in cancers of other reproductive tissues. As the body of literature expands, examining relaxin expression in cancerous tissues and its role in a growing number of in vitro and in vivo cancer models, our understanding of the important involvement of this hormone in cancer biology is becoming clearer. Specifically, the pleiotropic functions of relaxin affecting cell growth, angiogenesis, blood flow, cell migration and extracellular matrix remodeling are examined in the context of cancer progression. The interactions and intercepts of the intracellular signalling pathways of relaxin with the androgen pathway are explored in the context of progression of castration-resistant and androgen-independent prostate cancers. We provide an overview of current anti-hormonal therapeutic treatment options for prostate cancer and delve into therapeutic approaches and development of agents aimed at specifically antagonizing relaxin signalling to curb tumor growth. We also discuss the rationale and challenges utilizing such agents as novel anti-hormonals in the clinic, and their potential to supplement current therapeutic modalities. © 2014 UICC.

  5. Combination Therapy Improves Survival in Prostate Cancer Model | Center for Cancer Research

    Cancer.gov

    Surgery and radiotherapy are the recommended treatments for localized prostate cancer. Recurrent prostate cancer, however, is often treated with androgen-deprivation therapy. Most patients who undergo this type of therapy eventually develop castration-resistant prostate cancer (CRPC). Though initially androgen-related therapies for CRPC had been thought to be ineffective, further studies have demonstrated that the disease remains dependent on the signaling of androgens, such as testosterone, for its continued progression. This development suggests that alternative strategies for manipulating androgen signaling may prove useful for treating CRPC.

  6. Parametric PET/MR Fusion Imaging to Differentiate Aggressive from Indolent Primary Prostate Cancer with Application for Image-Guided Prostate Cancer Biopsies

    DTIC Science & Technology

    2013-10-01

    AD_________________ Award Number: W81XWH-12-1-0597 TITLE: Parametric PET /MR Fusion Imaging to...Parametric PET /MR Fusion Imaging to Differentiate Aggressive from Indolent Primary Prostate Cancer with Application for Image-Guided Prostate Cancer Biopsies...The study investigates whether fusion PET /MRI imaging with 18F-choline PET /CT and diffusion-weighted MRI can be successfully applied to target prostate

  7. Absolute Effect of Prostate Cancer Screening: Balance of benefits and harms by center within the European Randomized Study of Prostate Cancer Screening

    PubMed Central

    Auvinen, Anssi; Moss, Sue M; Tammela, Teuvo L J; Taari, Kimmo; Roobol, Monique J; Schröder, Fritz H; Bangma, Chris H; Carlsson, Sigrid; Aus, Gunnar; Zappa, Marco; Puliti, Donella; Denis, Louis J; Nelen, Vera; Kwiatkowski, Maciej; Randazzo, Marco; Paez, Alvaro; Lujan, Marcos; Hugosson, Jonas

    2016-01-01

    Purpose The balance of benefits and harms in prostate cancer screening has not been sufficiently characterized. We related indicators of mortality reduction and overdetection by center within the European Randomized Study of Prostate Cancer Screening. Experimental Design We analyzed the absolute mortality reduction expressed as number needed to invite (NNI=1/absolute risk reduction; indicating how many men had to be randomized to screening arm to avert a prostate cancer death) for screening and the absolute excess of prostate cancer detection as number needed for overdetection (NNO=1/absolute excess incidence; indicating the number of men invited per additional prostate cancer case), and compared their relationship across the seven ERSPC centers. Results Both absolute mortality reduction (NNI) and absolute overdetection (NNO) varied widely between the centers: NNI 200-7000 and NNO 16-69. Extent of overdiagnosis and mortality reduction were closely associated (correlation coefficient r=0.76, weighted linear regression coefficient β=33, 95% 5-62, R2=0.72). For an averted prostate cancer death at 13 years of follow-up, 12-36 excess cases had to be detected in various centers. Conclusions The differences between the ERSPC centers likely reflect variations in prostate cancer incidence and mortality, as well as in screening protocol and performance. The strong interrelation between the benefits and harms suggests that efforts to maximize the mortality effect are bound to increase overdiagnosis, and might be improved by focusing on high-risk populations. The optimal balance between screening intensity and risk of overdiagnosis remains unclear. PMID:26289069

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

    PubMed

    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.

  9. LIGHT-ing Up Prostate Cancer for Immunotherapy

    DTIC Science & Technology

    2016-10-01

    Award Number: W81XWH-15-1-0491 TITLE: LIGHT -ing up prostate cancer for immunotherapy PRINCIPAL INVESTIGATOR: W. Martin Kast, Ph.D...FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2016 2. REPORT TYPE Annual 3. DATES COVERED 4. TITLE AND SUBTITLE LIGHT -ing up prostate cancer...expression of LIGHT molecules within the tumor milieu counteracts cancer immune-evasion mechanisms and instigates activation and migration of T-cells

  10. The Use of Biomarkers in Prostate Cancer Screening and Treatment

    PubMed Central

    Alford, Ashley V.; Brito, Joseph M.; Yadav, Kamlesh K.; Yadav, Shalini S.; Tewari, Ashutosh K.; Renzulli, Joseph

    2017-01-01

    Prostate cancer screening and diagnosis has been guided by prostate-specific antigen levels for the past 25 years, but with the most recent US Preventive Services Task Force screening recommendations, as well as concerns regarding overdiagnosis and overtreatment, a new wave of prostate cancer biomarkers has recently emerged. These assays allow the testing of urine, serum, or prostate tissue for molecular signs of prostate cancer, and provide information regarding both diagnosis and prognosis. In this review, we discuss 12 commercially available biomarker assays approved for the diagnosis and treatment of prostate cancer. The results of clinical validation studies and clinical decision-making studies are presented. This information is designed to assist urologists in making clinical decisions with respect to ordering and interpreting these tests for different patients. There are numerous fluid and biopsy-based genomic tests available for prostate cancer patients that provide the physician and patient with different information about risk of future disease and treatment outcomes. It is important that providers be able to recommend the appropriate test for each individual patient; this decision is based on tissue availability and prognostic information desired. Future studies will continue to emphasize the important role of genomic biomarkers in making individualized treatment decisions for prostate cancer patients. PMID:29472826

  11. Relative value of race, family history and prostate specific antigen as indications for early initiation of prostate cancer screening.

    PubMed

    Vertosick, Emily A; Poon, Bing Ying; Vickers, Andrew J

    2014-09-01

    Many guidelines suggest earlier screening for prostate cancer in men at high risk, with risk defined in terms of race and family history. Recent evidence suggests that baseline prostate specific antigen is strongly predictive of the long-term risk of aggressive prostate cancer. We compared the usefulness of risk stratifying early screening by race, family history and prostate specific antigen at age 45 years. Using estimates from the literature we calculated the proportion of men targeted for early screening using family history, black race or prostate specific antigen as the criterion for high risk. We calculated the proportion of prostate cancer deaths that would occur in those men by age 75 years. Screening based on family history involved 10% of men, accounting for 14% of prostate cancer deaths. Using black race as a risk criterion involved 13% of men, accounting for 28% of deaths. In contrast, 44% of prostate cancer deaths occurred in the 10% of men with the highest prostate specific antigen at age 45 years. In no sensitivity analysis for race and family history did the ratio of risk group size to number of prostate cancer deaths in that risk group approach that of prostate specific antigen. Basing decisions for early screening on prostate specific antigen at age 45 years provided the best ratio between men screened and potential cancer deaths avoided. Given the lack of evidence that race or family history affects the relationship between prostate specific antigen and risk, prostate specific antigen based risk stratification would likely include any black men or men with a family history who are destined to experience aggressive disease. Differential screening based on risk should be informed by baseline prostate specific antigen. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

    PubMed

    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% (p<0.05). We need a differentiated approach to selecting treatment for patients with prostate cancer, especially of old age, including the option for active surveillance of patients with clinically insignificant prostate cancer.

  13. Identification of prostate cancer biomarkers in urinary exosomes

    PubMed Central

    Øverbye, Anders; Skotland, Tore; Koehler, Christian J.; Thiede, Bernd; Seierstad, Therese; Berge, Viktor; Sandvig, Kirsten; Llorente, Alicia

    2015-01-01

    Exosomes have recently appeared as a novel source of non-invasive cancer biomarkers since tumour-specific molecules can be found in exosomes isolated from biological fluids. We have here investigated the proteome of urinary exosomes by using mass spectrometry to identify proteins differentially expressed in prostate cancer patients compared to healthy male controls. In total, 15 control and 16 prostate cancer samples of urinary exosomes were analyzed. Importantly, 246 proteins were differentially expressed in the two groups. The majority of these proteins (221) were up-regulated in exosomes from prostate cancer patients. These proteins were analyzed according to specific criteria to create a focus list that contained 37 proteins. At 100% specificity, 17 of these proteins displayed individual sensitivities above 60%. Even though several of these proteins showed high sensitivity and specificity for prostate cancer as individual biomarkers, combining them in a multi-panel test has the potential for full differentiation of prostate cancer from non-disease controls. The highest sensitivity, 94%, was observed for transmembrane protein 256 (TM256; chromosome 17 open reading frame 61). LAMTOR proteins were also distinctly enriched with very high specificity for patient samples. TM256 and LAMTOR1 could be used to augment the sensitivity to 100%. Other prominent proteins were V-type proton ATPase 16 kDa proteolipid subunit (VATL), adipogenesis regulatory factor (ADIRF), and several Rab-class members and proteasomal proteins. In conclusion, this study clearly shows the potential of using urinary exosomes in the diagnosis and clinical management of prostate cancer. PMID:26196085

  14. Identification of prostate cancer biomarkers in urinary exosomes.

    PubMed

    Øverbye, Anders; Skotland, Tore; Koehler, Christian J; Thiede, Bernd; Seierstad, Therese; Berge, Viktor; Sandvig, Kirsten; Llorente, Alicia

    2015-10-06

    Exosomes have recently appeared as a novel source of non-invasive cancer biomarkers since tumour-specific molecules can be found in exosomes isolated from biological fluids. We have here investigated the proteome of urinary exosomes by using mass spectrometry to identify proteins differentially expressed in prostate cancer patients compared to healthy male controls. In total, 15 control and 16 prostate cancer samples of urinary exosomes were analyzed. Importantly, 246 proteins were differentially expressed in the two groups. The majority of these proteins (221) were up-regulated in exosomes from prostate cancer patients. These proteins were analyzed according to specific criteria to create a focus list that contained 37 proteins. At 100% specificity, 17 of these proteins displayed individual sensitivities above 60%. Even though several of these proteins showed high sensitivity and specificity for prostate cancer as individual biomarkers, combining them in a multi-panel test has the potential for full differentiation of prostate cancer from non-disease controls. The highest sensitivity, 94%, was observed for transmembrane protein 256 (TM256; chromosome 17 open reading frame 61). LAMTOR proteins were also distinctly enriched with very high specificity for patient samples. TM256 and LAMTOR1 could be used to augment the sensitivity to 100%. Other prominent proteins were V-type proton ATPase 16 kDa proteolipid subunit (VATL), adipogenesis regulatory factor (ADIRF), and several Rab-class members and proteasomal proteins. In conclusion, this study clearly shows the potential of using urinary exosomes in the diagnosis and clinical management of prostate cancer.

  15. The Infectious Pathogenesis Of Prostate Cancer

    DTIC Science & Technology

    2011-04-01

    agents in the genesis of inflammation. For prostate cancer, several lines of evidence point to a role of infections as important agents , although no...specific infection has consistently been identified. In this project, we are examining two specific infectious agents with respect to prostate cancer: T...Infectious agents are likely targets involved in the initiation and exacerbation of chronic inflammation, and infections can lead to increased risk of

  16. Prostate Cancer Genetics in African Americans

    DTIC Science & Technology

    2014-09-01

    ADDRESS. 1. REPORT DATE 2 . REPORT TYPE Annual 3. DATES COVERED 15 Aug 2013 – 14 Aug 2014 4. TITLE AND SUBTITLE Prostate Cancer Genetics in...first two years of this grant has involved (1) hiring and training of culturally competent research personnel; ( 2 ) the establishment of a project...was no indication of familial prostate cancer. Task 2 : Data Collection and Management (Years 1- 3) The study-specific database has been

  17. The long tail of oncogenic drivers in prostate cancer.

    PubMed

    Armenia, Joshua; Wankowicz, Stephanie A M; Liu, David; Gao, Jianjiong; Kundra, Ritika; Reznik, Ed; Chatila, Walid K; Chakravarty, Debyani; Han, G Celine; Coleman, Ilsa; Montgomery, Bruce; Pritchard, Colin; Morrissey, Colm; Barbieri, Christopher E; Beltran, Himisha; Sboner, Andrea; Zafeiriou, Zafeiris; Miranda, Susana; Bielski, Craig M; Penson, Alexander V; Tolonen, Charlotte; Huang, Franklin W; Robinson, Dan; Wu, Yi Mi; Lonigro, Robert; Garraway, Levi A; Demichelis, Francesca; Kantoff, Philip W; Taplin, Mary-Ellen; Abida, Wassim; Taylor, Barry S; Scher, Howard I; Nelson, Peter S; de Bono, Johann S; Rubin, Mark A; Sawyers, Charles L; Chinnaiyan, Arul M; Schultz, Nikolaus; Van Allen, Eliezer M

    2018-05-01

    Comprehensive genomic characterization of prostate cancer has identified recurrent alterations in genes involved in androgen signaling, DNA repair, and PI3K signaling, among others. However, larger and uniform genomic analysis may identify additional recurrently mutated genes at lower frequencies. Here we aggregate and uniformly analyze exome sequencing data from 1,013 prostate cancers. We identify and validate a new class of E26 transformation-specific (ETS)-fusion-negative tumors defined by mutations in epigenetic regulators, as well as alterations in pathways not previously implicated in prostate cancer, such as the spliceosome pathway. We find that the incidence of significantly mutated genes (SMGs) follows a long-tail distribution, with many genes mutated in less than 3% of cases. We identify a total of 97 SMGs, including 70 not previously implicated in prostate cancer, such as the ubiquitin ligase CUL3 and the transcription factor SPEN. Finally, comparing primary and metastatic prostate cancer identifies a set of genomic markers that may inform risk stratification.

  18. FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer.

    PubMed

    Davidsson, Sabina; Andren, Ove; Ohlson, Anna-Lena; Carlsson, Jessica; Andersson, Swen-Olof; Giunchi, Francesca; Rider, Jennifer R; Fiorentino, Michelangelo

    2018-01-01

    The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (T regs ). In the present study we evaluated the prevalence of T reg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer. Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4 + T regs and CD8 + T regs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of T regs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area. In men with prostate cancer, similarly high numbers of stromal CD4 + T regs were identified in PAH and tumor, but CD4 + T regs were less common in PIN. Greater numbers of epithelial CD4+ T regs in normal prostatic tissue were positively associated with both Gleason score and pT-stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4 + T regs in the normal prostatic tissue counterpart. Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4 + T regs and indicate that transformation of the anti-tumor immune response may be initiated even before the primary tumor is established. © 2017 The Authors. The Prostate Published by Wiley Periodicals Inc.

  19. Prostate Cancer Prevention (PDQ®)—Health Professional Version

    Cancer.gov

    Prostate cancer prevention strategies include avoiding risk factors, increasing protective factors, and considering chemoprevention when appropriate. Get detailed information about factors that influence the risk of prostate cancer and research aimed at preventing it in this clinician summary.

  20. Feasibility of Prostate Cancer Diagnosis by Transrectal Photoacoustic Imaging

    DTIC Science & Technology

    2012-03-01

    cancer detection; needle biopsy is the current practice for diagnosis of the disease, aiming randomly in the prostate. Transrectal ultrasound has...been used as a guiding tool to direct tissue needle biopsy for prostate cancer diagnosis; it cannot be utilized for detecting prostate cancer due to...Research Systems, CA) and used as a reference signal. The sample and the ultrasound transducer (UST, Olympus NDT, one inch in focal length) are

  1. Care Planning for Prostate Cancer Patients on Active Surveillance

    DTIC Science & Technology

    2016-10-01

    intervention (PCPEP) for prostate cancer patients on active surveillance ( Study Specific Aim 1). As part of the adoption process, we will: (Aim 1a...evaluate the acceptability and feasibility of the program with prostate cancer patients on active surveillance in a small pilot study ( Study Specific...to a poster depicting the study finding on “Treatment 4 Decision-making and Adherence to Active Surveillance in Prostate Cancer Patients” presented

  2. Laser Illumination Modality of Photoacoustic Imaging Technique for Prostate Cancer

    NASA Astrophysics Data System (ADS)

    Peng, Dong-qing; Peng, Yuan-yuan; Guo, Jian; Li, Hui

    2016-02-01

    Photoacoustic imaging (PAI) has recently emerged as a promising imaging technique for prostate cancer. But there was still a lot of challenge in the PAI for prostate cancer detection, such as laser illumination modality. Knowledge of absorbed light distribution in prostate tissue was essential since the distribution characteristic of absorbed light energy would influence the imaging depth and range of PAI. In order to make a comparison of different laser illumination modality of photoacoustic imaging technique for prostate cancer, optical model of human prostate was established and combined with Monte Carlo simulation method to calculate the light absorption distribution in the prostate tissue. Characteristic of light absorption distribution of transurethral and trans-rectal illumination case, and of tumor at different location was compared with each other.The relevant conclusions would be significant for optimizing the light illumination in a PAI system for prostate cancer detection.

  3. Prostate cancer epigenetics and its clinical implications

    PubMed Central

    Yegnasubramanian, Srinivasan

    2016-01-01

    Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy. PMID:27212125

  4. Prostate cancer epigenetics and its clinical implications.

    PubMed

    Yegnasubramanian, Srinivasan

    2016-01-01

    Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy.

  5. Multiplex biomarker approach for determining risk of prostate-specific antigen-defined recurrence of prostate cancer.

    PubMed

    Rhodes, Daniel R; Sanda, Martin G; Otte, Arie P; Chinnaiyan, Arul M; Rubin, Mark A

    2003-05-07

    Molecular signatures in cancer tissue may be useful for diagnosis and are associated with survival. We used results from high-density tissue microarrays (TMAs) to define combinations of candidate biomarkers associated with the rate of prostate cancer progression after radical prostatectomy that could identify patients at high risk for recurrence. Fourteen candidate biomarkers for prostate cancer for which antibodies are available included hepsin, pim-1 kinase, E-cadherin (ECAD; cell adhesion molecule), alpha-methylacyl-coenzyme A racemase, and EZH2 (enhancer of zeste homolog 2, a transcriptional repressor). TMAs containing more than 2000 tumor samples from 259 patients who underwent radical prostatectomy for localized prostate cancer were studied with these antibodies. Immunohistochemistry results were evaluated in conjunction with clinical parameters associated with prostate cancer progression, including tumor stage, Gleason score, and prostate-specific antigen (PSA) level. Recurrence was defined as a postsurgery PSA level of more than 0.2 ng/mL. All statistical tests were two-sided. Moderate or strong expression of EZH2 coupled with at most moderate expression of ECAD (i.e., a positive EZH2:ECAD status) was the biomarker combination that was most strongly associated with the recurrence of prostate cancer. EZH2:ECAD status was statistically significantly associated with prostate cancer recurrence in a training set of 103 patients (relative risk [RR] = 2.52, 95% confidence interval [CI] = 1.09 to 5.81; P =.021), in a validation set of 80 patients (RR = 3.72, 95% CI = 1.27 to 10.91; P =.009), and in the combined set of 183 patients (RR = 2.96, 95% CI = 1.56 to 5.61; P<.001). EZH2:ECAD status was statistically significantly associated with disease recurrence even after adjusting for clinical parameters, such as tumor stage, Gleason score, and PSA level (hazard ratio = 3.19, 95% CI = 1.50 to 6.77; P =.003). EZH2:ECAD status was statistically significantly associated

  6. Biomarkers identified for prostate cancer patients through genome-scale screening.

    PubMed

    Wang, Lei-Yun; Cui, Jia-Jia; Zhu, Tao; Shao, Wei-Hua; Zhao, Yi; Wang, Sai; Zhang, Yu-Peng; Wu, Ji-Chu; Zhang, Le

    2017-11-03

    Prostate cancer is a threat to men and usually occurs in aged males. Though prostate specific antigen level and Gleason score are utilized for evaluation of the prostate cancer in clinic, the biomarkers for this malignancy have not been widely recognized. Furthermore, the outcome varies across individuals receiving comparable treatment regimens and the underlying mechanism is still unclear. We supposed that genetic feature may be responsible for, at least in part, this process and conducted a two-cohort study to compare the genetic difference in tumorous and normal tissues of prostate cancer patients. The Gene Expression Omnibus dataset were used and a total of 41 genes were found significantly differently expressed in tumor tissues as compared with normal prostate tissues. Four genes (SPOCK3, SPON1, PTN and TGFB3) were selected for further evaluation after Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis and clinical association analysis. MIR1908 was also found decreased expression level in prostate cancer whose target genes were found expressing in both prostate tumor and normal tissues. These results indicated that these potential biomarkers deserve attention in prostate cancer patients and the underlying mechanism should be further investigated.

  7. Probing the prostate tumour microenvironment I: impact of glucose deprivation on a cell model of prostate cancer progression

    PubMed Central

    Tonry, Claire; Armstrong, John; Pennington, Stephen R.

    2017-01-01

    In the developed world, prostate cancer is the most common cancer diagnosis in men. Although prostate cancer initially presents as a non life-threatening disease, 90% of patients will develop castration resistant prostate cancer (CRPC), which preludes distant metastasis and is largely accountable for prostate cancer associated deaths. This is because as yet, there are no viable molecular therapeutic targets for effective treatment of CRPC. It is now widely accepted that cancer cells can alter their metabolic profile during the course of tumourgenesis and metastasis such that they are able to survive in oxygen and nutrient-poor environments. This work was aimed towards gaining greater mechanistic understanding of how such stresses in the tumour microenvironment impact on both androgen sensitive (LNCaP) and androgen independent (LNCaP-abl and LNCaP-abl-Hof) prostate cancer cell lines. Here we have applied technically robust and reproducible label-free liquid chromatography mass spectrometry analysis for comprehensive proteomic profiling of prostate cancer cell lines under nutrient deficient (low glucose) conditions. This led to the identification of approximately 4,000 proteins - one of the largest protein datasets for prostate cancer cell lines established to date. The biological and clinical significance of proteins showing a significant change in expression as result of low glucose conditions was established. Novel, intuitive workflows were subsequently implemented to ensure the verification of selected proteins of interest in a robust, reproducible and high throughput manner. Overall, these data suggest that this strategy supports identification of protein biomarkers of prostate cancer progression and potential therapeutic targets for CRPC. PMID:28086232

  8. Radical Prostatectomy versus Observation for Localized Prostate Cancer

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    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.

  10. Renal donors with prostate cancer, no longer a reason to decline.

    PubMed

    Dholakia, S; Johns, R; Muirhead, L; Papalois, V; Crane, J

    2016-01-01

    To fully assess the true risk of prostate cancer transmission in during renal transplantation. A full review of all existing literature relevant to the topic. There has not been a single documented case of transmission of prostate cancer during renal transplant. Prostate cancer in deceased organ donors has an incidence estimated between 3% and 18.5% and over 100 transplants have been performed using organs from donor with proven prostate cancer without issue. Transmission of prostate cancer through kidney transplantation seems very unlikely. The risks of remaining on the waiting list are outweighed by a transmission risk and the potential benefit makes the case to have clear guidelines about donor prostate malignancy when accepting potential organs. Copyright © 2015. Published by Elsevier Inc.

  11. Treatment Option Overview (Prostate Cancer)

    MedlinePlus

    ... from making testosterone. However, estrogens are seldom used today in the treatment of prostate cancer because of ... or better than the standard treatment . Many of today's standard treatments for cancer are based on earlier ...

  12. Hormone therapy for prostate cancer

    MedlinePlus

    ... be used: Before radiation or surgery to help shrink tumors Along with radiation therapy for cancer that ... of most androgens in the body. This also shrinks or stops prostate cancer from growing. While effective, ...

  13. Brachytherapy in early prostate cancer--early experience.

    PubMed

    Jose, B O; Bailen, J L; Albrink, F H; Steinbock, G S; Cornett, M S; Benson, D C; Schmied, W K; Medley, R N; Spanos, W J; Paris, K J; Koerner, P D; Gatenby, R A; Wilson, D L; Meyer, R

    1999-01-01

    Use of brachytherapy with radioactive seeds in the management of early prostate cancer is commonly used in the United States. The early experience has been reported from the prostate treatment centers in Seattle for the last 10 years. In this manuscript we are reporting our early experience of 150 radioactive seed implantations in early stage prostate cancer using either Iodine 125 or Palladium 103 seeds. The average age of the patient is 66 years and the median Gleason score is 5.4 with a median PSA of 6. A brief description of the evolution of the treatment of prostate cancer as well as the preparation for the seed implantation using the volume study with ultrasound of the prostate, pubic arch study using CT scan of the pelvis and the complete planning using the treatment planning computers are discussed. We also have described the current technique which is used in our experience based on the Seattle guidelines. We plan a follow-up report with the results of the studies with longer follow-up.

  14. Identification of Novel Prostate Cancer-Causitive Gene Mutations by Representational Difference Analysis of Microdissected Prostate Cancer

    DTIC Science & Technology

    2001-03-01

    paired samples of microdissected benign and malignant prostate epithelium. The resulting subtraction products were cloned and screened in Southern blots... benign and malignant human prostate cancer. Data is given to show that microdissected tissue samples retain RNA of sufficient quality to perform gene

  15. Alzheimer's disease is associated with prostate cancer: a population-based study.

    PubMed

    Lin, Herng-Ching; Kao, Li-Ting; Chung, Shiu-Dong; Huang, Chung-Chien; Shia, Ben-Chang; Huang, Chao-Yuan

    2018-01-26

    Alzheimer's disease and cancer are increasingly prevalent with advancing age. However, the association between Alzheimer's disease and prostate cancer remains unclear. The aim of this study was to examine the relationship between prior Alzheimer's disease and subsequent prostate cancer using a population-based dataset in Taiwan. Data for this study were sourced from the Taiwan Longitudinal Health Insurance Database 2005. This case-control study included 2101 prostate cancer patients as cases and 6303 matched controls. We used conditional logistic regression analyses to calculate the odds ratio (OR) and corresponding 95% confidence interval (CI) for Alzheimer's disease between prostate cancer patients and controls. We found that of the 8404 sampled patients, 128 (1.5%) had been diagnosed with Alzheimer's disease prior to the index date. A Chi-squared test showed that there was a significant difference in the prevalences of prior Alzheimer's disease between prostate cancer patients and controls (2.1% vs. 1.3%, p < 0.001). The conditional logistic regression analysis showed that the OR of prior Alzheimer's disease for prostate cancer patients was 1.53 (95% CI: 1.06∼2.21) compared to controls. Furthermore, the OR of prior Alzheimer's disease for prostate cancer patients was 1.52 (95% CI: 1.04∼2.22) compared to controls after adjusting for hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, prostatitis, gonorrhea or chlamydia infection, testitis or epididymitis, and alcohol abuse/alcohol dependency syndrome. This study revealed an association between prior Alzheimer's disease and prostate cancer. We suggest that clinicians be alert to the increased risk of prostate cancer when caring for elderly individuals with Alzheimer's disease.

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

    PubMed

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

    2012-07-01

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

  17. Prognostic significance of obstructive uropathy in advanced prostate cancer.

    PubMed

    Oefelein, Michael G

    2004-06-01

    To report the incidence and prognostic implications of obstructive uropathy (OU) in patients with advanced prostate cancer receiving androgen deprivation therapy and to define the impact initial local therapy has on the development of OU in patients with prostate cancer who develop recurrence and begin androgen deprivation therapy. From a population of 260 patients with advanced prostate cancer diagnosed between 1986 and 2003, OU was identified in 51 patients. The OU treatment options included ureteral stent, percutaneous nephrostomy, transurethral resection of the prostate, Foley catheter placement, and urinary diversion. Overall survival and the factors that influenced survival were calculated using standard statistical methods. OU was diagnosed in 15 (16%) of 80 patients who received local therapy with curative intent and in whom local therapy subsequently failed and in 36 (19%) of 180 patients who had never received local therapy (P = 0.7, chi-square test). Of these 51 patients, 39 had bladder neck obstruction and 16 had ureteral obstruction. Overall survival was significantly worse for the men with OU compared with those without OU (41 versus 54 months). OU was associated with tumor stage and androgen-insensitive prostate cancer. OU results in significantly reduced survival in men with prostate cancer. In a select group of patients with prostate cancer with progression after local therapy (primarily radiotherapy), no statistically significant reduction in the development of OU was observed relative to patients matched for stage, grade, and pretreatment prostate-specific antigen level treated with androgen deprivation therapy alone. Aggressive advanced stage and hormone-insensitive disease are variables associated with OU.

  18. Vitamin D deficiency and insufficiency among patients with prostate cancer.

    PubMed

    Trump, Donald L; Chadha, Manpreet K; Sunga, Annette Y; Fakih, Marwan G; Ashraf, Umeer; Silliman, Carrie G; Hollis, Bruce W; Nesline, Mary K; Tian, Lili; Tan, Wei; Johnson, Candace S

    2009-10-01

    To assess the frequency of vitamin D deficiency among men with prostate cancer, as considerable epidemiological, in vitro, in vivo and clinical data support an association between vitamin D deficiency and prostate cancer outcome. The study included 120 ambulatory men with recurrent prostate cancer and 50 with clinically localized prostate cancer who were evaluated and serum samples assayed for 25-OH vitamin D levels. Then 100 controls (both sexes), matched for age and season of serum sample, were chosen from a prospective serum banking protocol. The relationship between age, body mass index, disease stage, Eastern Cooperative Oncology Group performance status, season and previous therapy on vitamin D status were evaluated using univariate and multivariate analyses. The mean 25-OH vitamin D level was 25.9 ng/mL in those with recurrent disease, 27.5 ng/mL in men with clinically localized prostate cancer and 24.5 ng/mL in controls. The frequency of vitamin D deficiency (<20 ng/mL) and insufficiency (20-31 ng/mL) was 40% and 32% in men with recurrent prostate; 28% had vitamin D levels that were normal (32-100 ng/mL). Among men with localized prostate cancer, 18% were deficient, 50% were insufficient and 32% were normal. Among controls, 31% were deficient, 40% were insufficient and 29% were normal. Metastatic disease (P = 0.005) and season of blood sampling (winter/spring; P = 0.01) were associated with vitamin D deficiency in patients with prostate cancer, while age, race, performance status and body mass index were not. Vitamin D deficiency and insufficiency were common among men with prostate cancer and apparently normal controls in the western New York region.

  19. Treatment- and Disease-Related Complications of Prostate Cancer

    PubMed Central

    Simoneau, Anne R

    2006-01-01

    One of the highlights of the 16th International Prostate Cancer Update was a session on treatment- and disease-related complications of prostate disease. It began with presentation of a challenging case of rising prostate-specific antigen levels after radical prostatectomy, followed by an overview of the use of zoledronic acid in prostate cancer, a review of side effects of complementary medicines, an overview of complications of cryotherapy, an assessment of complications of brachytherapy and external beam radiation therapy, and a comparison of laparoscopy versus open prostatectomy. PMID:17021643

  20. Timp3 loss accelerates tumour invasion and increases prostate inflammation in a mouse model of prostate cancer.

    PubMed

    Adissu, Hibret A; McKerlie, Colin; Di Grappa, Marco; Waterhouse, Paul; Xu, Qiang; Fang, Hui; Khokha, Rama; Wood, Geoffrey A

    2015-12-01

    Altered expression and activity of proteases is implicated in inflammation and cancer progression. An important negative regulator of protease activity is TIMP3 (tissue inhibitor of metalloproteinase 3). TIMP3 expression is lacking in many cancers including advanced prostate cancer, and this may facilitate invasion and metastasis by allowing unrestrained protease activity. To investigate the role of TIMP3 in prostate cancer progression, we crossed TIMP3-deficient mice (Timp3(-/-)) to mice with prostate-specific deletion of the tumor suppressor Pten (Pten(-/-)), a well-established mouse model of prostate cancer. Tumor growth and progression were compared between Pten(-/-), Timp3(-/-) and control (Pten(-/-), Timp3(+/+)) mice at 16 weeks of age by histopathology and markers of proliferation, vascularity, and tumor invasion. Metalloproteinase activity within the tumors was assessed by gelatin zymography. Inflammatory infiltrates were assessed by immunohistochemistry for macrophages and lymphocytes whereas expression of cytokines and other inflammatory mediators was assessed by quantitative real time PCR and multiplex ELISA. Increased tumor growth, proliferation index, increased microvascular density, and invasion was observed in Pten(-/-), Timp3(-/-) prostate tumors compared to Pten(-/-), Timp3(+/+) tumors. Tumor cell invasion in Pten(-/-), Timp3(-/-) mice was associated with increased expression of matrix metalloprotease (MMP)-9 and activation of MMP-2. There was markedly increased inflammatory cell infiltration into the TIMP3-deficient prostate tumors along with increased expression of monocyte chemoattractant protein-1, cyclooxygenase-2, TNF-α, and interleukin-1β; all of which are implicated in inflammation and cancer. This study provides important insights into the role of altered protease activity in promoting prostate cancer invasion and implicates prostate inflammation as an important promoting factor in prostate cancer progression. © 2015 Wiley Periodicals

  1. The lived experience of men diagnosed with prostate cancer.

    PubMed

    Krumwiede, Kelly A; Krumwiede, Norma

    2012-09-01

    To investigate the lived experience of prostate cancer from a patient perspective. Descriptive, qualitative. Community setting. 10 men with prostate cancer aged 62-70 years. A hermeneutic phenomenologic method using semistructured, open-ended questions addressing the lived experience. Phenomenology of praxis proposed by van Manen guided the data analysis and transformed personal experiences into disciplinary understanding. The use of van Manen's method of inquiry and analysis has contributed to the findings of the study by providing a way to explore the meaning of the lived experiences in an attempt to understand living with prostate cancer. Several themes were identified: living in the unknown, yearning to understand and know, struggling with unreliability of body, bearing the diagnosis of cancer, shifting priorities in the gap, and feeling comfort in the presence of others. Oncology nurses can use van Manen's four fundamental existentials-lived space (spatiality), lived body (corporeality), lived time (temporality), and lived other (relationality)-to understand the lived experience of prostate cancer. Nurses have many opportunities to impact the lives of men diagnosed with prostate cancer, including diagnosis, management of physical integrity, management of psychosocial integrity, and providing education. Nurses may encourage men to describe their diagnosis story and illness experience to better understand the meaning of the prostate cancer experience and to provide appropriate nursing care.

  2. Glycosylation potential of human prostate cancer cell lines

    PubMed Central

    Gao, Yin; Chachadi, Vishwanath B.; Cheng, Pi-Wan

    2014-01-01

    Altered glycosylation is a universal feature of cancer cells and altered glycans can help cancer cells escape immune surveillance, facilitate tumor invasion, and increase malignancy. The goal of this study was to identify specific glycoenzymes, which could distinguish prostate cancer cells from normal prostatic cells. We investigated enzymatic activities and gene expression levels of key glycosyl- and sulfotransferases responsible for the assembly of O- and N-glycans in several prostatic cells. These cells included immortalized RWPE-1 cells derived from normal prostatic tissues, and prostate cancer cells derived from metastasis in bone (PC-3), brain (DU145), lymph node (LNCaP), and vertebra (VCaP). We found that all cells were capable of synthesizing complex N-glycans and O-glycans with the core 1 structure, and each cell line had characteristic bio-synthetic pathways to modify these structures. The in vitro measured activities corresponded well to the mRNA levels of glycosyltransferases and sulfotransferases. Lectin and antibody binding to whole cells supported these results, which form the basis for the development of tumor cell-specific targeting strategies. PMID:22843320

  3. Heterobivalent Imaging Agents Targeting Prostate Cancer Training

    DTIC Science & Technology

    2011-06-01

    has been implicated as a salient player in the pathobiology of cancers of epithelial origin, e.g. prostate, cervix , ovarian, colon and...ANSI Std. Z39.18 W81XWH-10-1-0481 Heterobivalent Imaging Agents Targeting Prostate Cancer Training Aaron LeBeau University of California, San...Francisco San Francisco, CA 94103 Annual Summary 31 MAY 2010 - 1JUN 201101-06-2011 To determine the utility of imaging MT-SP1 in cancer , xenografts of

  4. Effect of Diabetes and Obesity on Disparities in Prostate Cancer Outcomes

    DTIC Science & Technology

    2016-10-01

    AWARD NUMBER: W81XWH-14-1-0503 TITLE: Effect of Diabetes and Obesity on Disparities in Prostate Cancer Outcomes PRINCIPAL INVESTIGATOR: Bettina F...Effect of Diabetes and Obesity on Disparities in Prostate Cancer Outcomes 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0503 5c. PROGRAM ELEMENT...prostate cancer related death by identifying potential modifiable factors. 15. SUBJECT TERMS Prostate cancer, disparities, VHA and VACCR data, obesity

  5. Non-Coding RNAs in Castration-Resistant Prostate Cancer: Regulation of Androgen Receptor Signaling and Cancer Metabolism.

    PubMed

    Shih, Jing-Wen; Wang, Ling-Yu; Hung, Chiu-Lien; Kung, Hsing-Jien; Hsieh, Chia-Ling

    2015-12-04

    Hormone-refractory prostate cancer frequently relapses from therapy and inevitably progresses to a bone-metastatic status with no cure. Understanding of the molecular mechanisms conferring resistance to androgen deprivation therapy has the potential to lead to the discovery of novel therapeutic targets for type of prostate cancer with poor prognosis. Progression to castration-resistant prostate cancer (CRPC) is characterized by aberrant androgen receptor (AR) expression and persistent AR signaling activity. Alterations in metabolic activity regulated by oncogenic pathways, such as c-Myc, were found to promote prostate cancer growth during the development of CRPC. Non-coding RNAs represent a diverse family of regulatory transcripts that drive tumorigenesis of prostate cancer and various other cancers by their hyperactivity or diminished function. A number of studies have examined differentially expressed non-coding RNAs in each stage of prostate cancer. Herein, we highlight the emerging impacts of microRNAs and long non-coding RNAs linked to reactivation of the AR signaling axis and reprogramming of the cellular metabolism in prostate cancer. The translational implications of non-coding RNA research for developing new biomarkers and therapeutic strategies for CRPC are also discussed.

  6. Non-Coding RNAs in Castration-Resistant Prostate Cancer: Regulation of Androgen Receptor Signaling and Cancer Metabolism

    PubMed Central

    Shih, Jing-Wen; Wang, Ling-Yu; Hung, Chiu-Lien; Kung, Hsing-Jien; Hsieh, Chia-Ling

    2015-01-01

    Hormone-refractory prostate cancer frequently relapses from therapy and inevitably progresses to a bone-metastatic status with no cure. Understanding of the molecular mechanisms conferring resistance to androgen deprivation therapy has the potential to lead to the discovery of novel therapeutic targets for type of prostate cancer with poor prognosis. Progression to castration-resistant prostate cancer (CRPC) is characterized by aberrant androgen receptor (AR) expression and persistent AR signaling activity. Alterations in metabolic activity regulated by oncogenic pathways, such as c-Myc, were found to promote prostate cancer growth during the development of CRPC. Non-coding RNAs represent a diverse family of regulatory transcripts that drive tumorigenesis of prostate cancer and various other cancers by their hyperactivity or diminished function. A number of studies have examined differentially expressed non-coding RNAs in each stage of prostate cancer. Herein, we highlight the emerging impacts of microRNAs and long non-coding RNAs linked to reactivation of the AR signaling axis and reprogramming of the cellular metabolism in prostate cancer. The translational implications of non-coding RNA research for developing new biomarkers and therapeutic strategies for CRPC are also discussed. PMID:26690121

  7. Optoacoustic imaging of an animal model of prostate cancer

    NASA Astrophysics Data System (ADS)

    Patterson, Michelle P.; Arsenault, Michel; Riley, Chris; Kolios, Michael; Whelan, William M.

    2010-02-01

    Prostate cancer is currently the most common cancer among Canadian men. Due to an increase in public awareness and screening, prostate cancer is being detected at earlier stages and in much younger men. This is raising the need for better treatment monitoring approaches. Optoacoustic imaging is a new technique that involves exposing tissues to pulsed light and detecting the acoustic waves generated by the tissue. Optoacoustic images of a tumour bearing mouse and an agematched control were acquired for a 775 nm illumination using a reverse-mode imaging system. A murine model of prostate cancer, TRAMP (transgenetic adenocarcinoma of mouse prostate), was investigated. The results show an increase in optoacoustic signal generated by the tumour compared to that generated by the surrounding tissues with a contrast ratio of 3.5. The dimensions of the tumour in the optoacoustic image agreed with the true tumour dimensions to within 0.5 mm. In this study we show that there are detectable changes in optoacoustic signal strength that arise from the presence of a tumour in the prostate, which demonstrates the potential of optoacoustic imaging for the monitoring of prostate cancer therapy.

  8. Prostate Cancer MR Imaging

    NASA Astrophysics Data System (ADS)

    Fütterer, Jurgen J.

    With a total of 192,280 new cases predicted for 2009, prostate cancer (PC) now accounts for 25% of all new male cancers diagnosed in the United States [1]. Furthermore, in their lifetime, one in six men will be clinically diagnosed with having PC, although many more men are found to have histological evidence of PC at autopsy [2,3,4]. Presently, approximately 1 in 10 men will die of PC [5,6]. The ever-aging population and wider spread use of the blood prostate-specific antigen (PSA) test [7,8], as well as the tendency to apply lower cut-off levels for this test [9], will further increase the diagnosis of this disease [10].

  9. Prostate cancer prevention agent development: Criteria and pipeline for candidate chemoprevention agents.

    PubMed

    Nelson, W G; Wilding, G

    2001-04-01

    Epidemiologic data suggest that prostate cancer morbidity and mortality ought to be preventable. New insights into the molecular pathogenesis of prostate cancer offer new opportunities for the discovery of prostate cancer chemoprevention drugs and new challenges for their development. Established pathways that lead to US Food and Drug Administration (FDA) approval of drugs for advanced prostate cancer may not be appropriate for the development of drugs for prostate cancer chemoprevention. For example, large randomized clinical trials designed to test the efficacy of new chemoprevention drugs on prostate cancer survival in the general population are likely to be conducted at great expense and take many years, threatening to increase commercial development risks while decreasing exclusive marketing revenues. As a consequence, to accelerate progress in research, new validated surrogate and strategic clinical trial endpoints, and new clinical trial designs featuring more precisely defined high-risk clinical trial cohorts, are needed. In this review, 10 criteria for prostate cancer chemoprevention agent development are offered and the pipeline of new prostate cancer chemoprevention drug candidates is considered.

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

    PubMed

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

    2014-12-01

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

  11. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer.

    PubMed

    Pritchard, Colin C; Mateo, Joaquin; Walsh, Michael F; De Sarkar, Navonil; Abida, Wassim; Beltran, Himisha; Garofalo, Andrea; Gulati, Roman; Carreira, Suzanne; Eeles, Rosalind; Elemento, Olivier; Rubin, Mark A; Robinson, Dan; Lonigro, Robert; Hussain, Maha; Chinnaiyan, Arul; Vinson, Jake; Filipenko, Julie; Garraway, Levi; Taplin, Mary-Ellen; AlDubayan, Saud; Han, G Celine; Beightol, Mallory; Morrissey, Colm; Nghiem, Belinda; Cheng, Heather H; Montgomery, Bruce; Walsh, Tom; Casadei, Silvia; Berger, Michael; Zhang, Liying; Zehir, Ahmet; Vijai, Joseph; Scher, Howard I; Sawyers, Charles; Schultz, Nikolaus; Kantoff, Philip W; Solit, David; Robson, Mark; Van Allen, Eliezer M; Offit, Kenneth; de Bono, Johann; Nelson, Peter S

    2016-08-04

    Inherited mutations in DNA-repair genes such as BRCA2 are associated with increased risks of lethal prostate cancer. Although the prevalence of germline mutations in DNA-repair genes among men with localized prostate cancer who are unselected for family predisposition is insufficient to warrant routine testing, the frequency of such mutations in patients with metastatic prostate cancer has not been established. We recruited 692 men with documented metastatic prostate cancer who were unselected for family history of cancer or age at diagnosis. We isolated germline DNA and used multiplex sequencing assays to assess mutations in 20 DNA-repair genes associated with autosomal dominant cancer-predisposition syndromes. A total of 84 germline DNA-repair gene mutations that were presumed to be deleterious were identified in 82 men (11.8%); mutations were found in 16 genes, including BRCA2 (37 men [5.3%]), ATM (11 [1.6%]), CHEK2 (10 [1.9% of 534 men with data]), BRCA1 (6 [0.9%]), RAD51D (3 [0.4%]), and PALB2 (3 [0.4%]). Mutation frequencies did not differ according to whether a family history of prostate cancer was present or according to age at diagnosis. Overall, the frequency of germline mutations in DNA-repair genes among men with metastatic prostate cancer significantly exceeded the prevalence of 4.6% among 499 men with localized prostate cancer (P<0.001), including men with high-risk disease, and the prevalence of 2.7% in the Exome Aggregation Consortium, which includes 53,105 persons without a known cancer diagnosis (P<0.001). In our multicenter study, the incidence of germline mutations in genes mediating DNA-repair processes among men with metastatic prostate cancer was 11.8%, which was significantly higher than the incidence among men with localized prostate cancer. The frequencies of germline mutations in DNA-repair genes among men with metastatic disease did not differ significantly according to age at diagnosis or family history of prostate cancer. (Funded by

  12. Isolation and Characterization of Prostate Cancer Stem Cells

    DTIC Science & Technology

    2011-08-01

    and ability to induce prostate tubule formation in vivo. FISH analysis of prostaspheres derived from patient specimens containing the TMPRSS-ERG...hybridization (FISH)[6]. Analysis of prostate tumor surgical cohorts have found 36-78% of prostate cancers possess the TMPRSS-ERG fusion[6]. We wondered...suggest that cancer stem/early progenitor cells can be expanded in our cultures. 6 To test the feasibility of this approach, FISH analysis was

  13. CDK5-A Novel Role in Prostate Cancer Immunotherapy

    DTIC Science & Technology

    2017-10-01

    of the involvement of a T cell antitumor response in impaired growth of prostate cancer in immunocompetent murine models of prostate cancer, and...of immune system activation by Cdk5 deletion in prostate cancer. We will confirm the involvement of a T cell antitumor response in impaired growth of...project? Major Task 1: Involvement of T cell anticancer immune response in impaired growth of TRAMP Cdk5-/- model. Months 1-10. Completed, month 10

  14. Effectiveness of the combined evaluation of KLK3 genetics and free-to-total prostate specific antigen ratio for prostate cancer diagnosis.

    PubMed

    Zambon, Carlo-Federico; Prayer-Galetti, Tommaso; Basso, Daniela; Padoan, Andrea; Rossi, Elisa; Secco, Silvia; Pelloso, Michela; Fogar, Paola; Navaglia, Filippo; Moz, Stefania; Zattoni, Filiberto; Plebani, Mario

    2012-10-01

    Of serum prostate specific antigen variability 40% depends on inherited factors. We ascertained whether the knowledge of KLK3 genetics would enhance prostate specific antigen diagnostic performance in patients with clinical suspicion of prostate cancer. We studied 1,058 men who consecutively underwent prostate biopsy for clinical suspicion of prostate cancer. At histology prostate cancer was present in 401 cases and absent in 657. Serum total prostate specific antigen and the free-to-total prostate specific antigen ratio were determined. Four polymorphisms of the KLK3 gene (rs2569733, rs2739448, rs925013 and rs2735839) and 1 polymorphism of the SRD5A2 gene (rs523349) were studied. The influence of genetics on prostate specific antigen variability was evaluated by multivariate linear regression analysis. The performance of total prostate specific antigen and the free-to-total prostate specific antigen ratio alone or combined with a genetically based patient classification were defined by ROC curve analyses. For prostate cancer diagnosis the free-to-total prostate specific antigen ratio index alone (cutoff 11%) was superior to total prostate specific antigen (cutoff 4 ng/ml) and to free-to-total prostate specific antigen ratio reflex testing (positive predictive value 61%, 43% and 54%, respectively). Prostate specific antigen correlated with KLK3 genetics (rs2735839 polymorphism p = 0.001, and rs2569733, rs2739448 and rs925013 haplotype combination p = 0.003). In patients with different KLK3 genetics 2 optimal free-to-total prostate specific antigen ratio cutoffs (11% and 14.5%) were found. For free-to-total prostate specific antigen ratio values between 11% and 14.5% the prostate cancer probability ranged from 30.0% to 47.4% according to patient genetics. The free-to-total prostate specific antigen ratio is superior to total prostate specific antigen for prostate cancer diagnosis, independent of total prostate specific antigen results. Free-to-total prostate

  15. [Urethral stricture rate after prostate cancer radiotherapy : Five-year data of a certified prostate cancer center].

    PubMed

    Kranz, J; Maurer, G; Maurer, U; Deserno, O; Schulte, S; Steffens, J

    2017-03-01

    A urethral stricture is a scar of the urethral epithelium which can cause obstructive voiding dysfunction with consequential damage of the upper urinary tract. Almost 45% of all strictures are iatrogenic; they develop in 2-9% of patients after radical prostatectomy, but can also occur after prostate cancer radiotherapy. This study provides 5‑year data of a certified prostate cancer center (PKZ) in terms of urethral strictures. Between 01/2008 and 12/2012 a total of 519 men were irradiated for prostate cancer (LDR and HDR brachytherapy as well as external beam radiation). The entire cohort was followed-up prospectively according to a standardized protocol (by type of irradiation). Short segment urethral strictures were treated by urethrotomy, recurrent and long segment stenosis with buccal mucosa urethroplasty. A total of 18 of 519 (3.4%) patients developed a urethral stricture post-therapeutically, which recurred in 66% of cases after the first operative treatment. The largest risk for developing a urethral stricture is attributed to the HDR brachytherapy (8.9%). Urethral strictures after prostate cancer radiotherapy should be diagnosed and treated in time for long-term preservation of renal function. The rate of radiogenic urethral strictures (3.4%) is equivalent to those after radical prostatectomy. Due to a high rate of recurrences, urethrotomy has a limited importance after irradiation.

  16. Dietary acrylamide and risk of prostate cancer

    PubMed Central

    Wilson, Kathryn M.; Giovannucci, Edward; Stampfer, Meir J.; Mucci, Lorelei A.

    2011-01-01

    Acrylamide has been designated by IARC as a “probable human carcinogen.” High levels are formed during cooking of many commonly consumed foods including French fries, potato chips, breakfast cereal, and coffee. Two prospective cohort studies and two case-control studies in Europe found no association between acrylamide intake and prostate cancer. We examined this association in a large prospective cohort of 47,896 U.S. men in the Health Professionals’ Follow-up Study, using updated dietary acrylamide intake from food frequency questionnaires in 1986, 1990, 1994, 1998, and 2002. From 1986 through 2006, we documented 5025 cases of prostate cancer, and 642 lethal cancers. We used Cox proportional hazards models to assess the association between acrylamide intake from diet and prostate cancer risk overall as well as risk of advanced or lethal cancer. Acrylamide intake ranged from a mean of 10.5 mcg/day in the lowest quintile to 40.1 mcg/day in the highest quintile; coffee and potato products were largest contributors to intake. The multivariate-adjusted relative risk of prostate cancer was 1.02 (95% confidence interval: 0.92–1.13) for the highest versus lowest quintile of acrylamide intake (p-value for trend=0.90). Results were similar when restricted to never smokers and to men who had PSA tests. There was no significant association for dietary acrylamide and risk of lethal, advanced, or high-grade disease, or for different latency periods ranging from 0–4 years to 12–16 years. We found no evidence that acrylamide intake, within the range of U.S. diets, is associated with increased risk of prostate cancer. PMID:21866549

  17. PSMA-Targeted Theranostic Nanocarrier for Prostate Cancer

    PubMed Central

    Flores, Orielyz; Santra, Santimukul; Kaittanis, Charalambos; Bassiouni, Rania; Khaled, Amr S; Khaled, Annette R.; Grimm, Jan; Perez, J Manuel

    2017-01-01

    Herein, we report the use of a theranostic nanocarrier (Folate-HBPE(CT20p)) to deliver a therapeutic peptide to prostate cancer tumors that express PSMA (folate hydrolase 1). The therapeutic peptide (CT20p) targets and inhibits the chaperonin-containing TCP-1 (CCT) protein-folding complex, is selectively cytotoxic to cancer cells, and is non-toxic to normal tissue. With the delivery of CT20p to prostate cancer cells via PSMA, a dual level of cancer specificity is achieved: (1) selective targeting to PSMA-expressing prostate tumors, and (2) specific cytotoxicity to cancer cells with minimal toxicity to normal cells. The PSMA-targeting theranostic nanocarrier can image PSMA-expressing cells and tumors when a near infrared dye is used as cargo. Meanwhile, it can be used to treat PSMA-expressing tumors when a therapeutic, such as the CT20p peptide, is encapsulated within the nanocarrier. Even when these PSMA-targeting nanocarriers are taken up by macrophages, minimal cell death is observed in these cells, in contrast with doxorubicin-based therapeutics that result in significant macrophage death. Incubation of PSMA-expressing prostate cancer cells with the Folate-HBPE(CT20p) nanocarriers induces considerable changes in cell morphology, reduction in the levels of integrin β1, and lower cell adhesion, eventually resulting in cell death. These results are relevant as integrin β1 plays a key role in prostate cancer invasion and metastatic potential. In addition, the use of the developed PSMA-targeting nanocarrier facilitates the selective in vivo delivery of CT20p to PSMA-positive tumor, inducing significant reduction in tumor size. PMID:28744329

  18. Opportunities for disease state management in prostate cancer.

    PubMed

    Pickard, A Simon; Hung, Shih-Ying; McKoy, June M; Witt, Whitney P; Arseven, Adnan; Sharifi, Roohollah; Wu, Zhigang; Knight, Sara J; McWilliams, Norene; Schumock, Glen T; Bennett, Charles L

    2005-08-01

    In this paper, we examine how the management of prostate cancer lends itself to a disease state management (DSM)-based approach, and propose a framework that emphasizes the patient-provider-caregiver triad in managing the long-term implications of the condition. There is often no clearly superior approach to the management of patients with prostate cancer (eg, watchful waiting and hormonal therapy), and each option entails different trade-offs in quality of life. Ideally, the physician and patient discuss the options, issues, and patient preferences for treatment through the shared decision-making process. A family caregiver such as the spouse of the patient is often involved in the treatment decision and in the long-term management of the cancer experience. In order to develop a DSM program supporting both patient and caregiver, educational, psychosocial, and health care system support needs should be tailored to each phase of cancer treatment/management. To embrace the unique aspects of prostate cancer management, the proposed framework emphasizes communication among the patient-caregiver-provider triad, inclusion of family caregivers in the program, cancer phase-specific support, and psychosocial services as a basis for implementation and evaluation of a DSM program in prostate cancer.

  19. Investigation of Interleukin-1β Polymorphisms in Prostate Cancer.

    PubMed

    Yencilek, Faruk; Yildirim, Asif; Yilmaz, Seda Gulec; Altinkilic, Emre Murat; Dalan, Altay Burak; Bastug, Yavuz; Isbir, Turgay

    2015-11-01

    Cytokine-mediated immune and inflammatory responses are considered to play an important role in the pathogenesis of prostate cancer. The present study investigated certain interleukin-1β (IL1β) polymorphisms and their association with prostate cancer. Genotyping of the IL1B-31(rs 1143627 G>A) and IL1B-511(rs 16944 Aprostate cancer (n=71) and controls (n=76). The frequency of the IL1B-31(rs1143627) AG heterozygote genotype was found to be significantly lower in patients compared to controls (odds ratio=0.648, 95% confidence interval=0.463-0.908; p=0.036). The genotypic frequencies of IL1B-511(rs16944) between prostate cancer patients and controls were statistically significantly different (p=0.001). The frequency of AG genotype for IL1B-511(rs16944) was 0.5-fold lower in patients with prostate cancer than in the controls (odds ratio=0.546; 95% confidence interval=0.377-0.791; p=0.001). Our data show that individuals carrying the IL1B-31(rs1143627) and IL1B-511(rs16944) AG genotypes had a decreased risk for developing prostate cancer. Out of all the possible combinations analyzed, IL1B-31(rs1143627) G with IL1B-511(rs16944) G combination had a protective association with prostate cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  20. AICAR induces AMPK-independent programmed necrosis in prostate cancer cells.

    PubMed

    Guo, Feng; Liu, Shuang-Qing; Gao, Xing-Hua; Zhang, Long-Yang

    2016-05-27

    AICAR (5-Aminoimidazole-4-carboxamide riboside or acadesine) is an AMP-activated protein kinase (AMPK) agonist, which induces cytotoxic effect to several cancer cells. Its potential activity in prostate cancer cells and the underlying signaling mechanisms have not been extensively studied. Here, we showed that AICAR primarily induced programmed necrosis, but not apoptosis, in prostate cancer cells (LNCaP, PC-3 and PC-82 lines). AICAR's cytotoxicity to prostate cancer cells was largely attenuated by the necrosis inhibitor necrostatin-1. Mitochondrial protein cyclophilin-D (CYPD) is required for AICAR-induced programmed necrosis. CYPD inhibitors (cyclosporin A and sanglifehrin A) as well as CYPD shRNAs dramatically attenuated AICAR-induced prostate cancer cell necrosis and cytotoxicity. Notably, AICAR-induced cell necrosis appeared independent of AMPK, yet requiring reactive oxygen species (ROS) production. ROS scavengers (N-acetylcysteine and MnTBAP), but not AMPKα shRNAs, largely inhibited prostate cancer cell necrosis and cytotoxicity by AICAR. In summary, the results of the present study demonstrate mechanistic evidences that AMPK-independent programmed necrosis contributes to AICAR's cytotoxicity in prostate cancer cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. FOXA1 promotes tumor progression in prostate cancer and represents a novel hallmark of castration-resistant prostate cancer.

    PubMed

    Gerhardt, Josefine; Montani, Matteo; Wild, Peter; Beer, Marc; Huber, Fabian; Hermanns, Thomas; Müntener, Michael; Kristiansen, Glen

    2012-02-01

    Forkhead box protein A1 (FOXA1) modulates the transactivation of steroid hormone receptors and thus may influence tumor growth and hormone responsiveness in prostate cancer. We therefore investigated the correlation of FOXA1 expression with clinical parameters, prostate-specific antigen (PSA) relapse-free survival, and hormone receptor expression in a large cohort of prostate cancer patients at different disease stages. FOXA1 expression did not differ significantly between benign glands from the peripheral zone and primary peripheral zone prostate carcinomas. However, FOXA1 was overexpressed in metastases and particularly in castration-resistant cases, but was expressed at lower levels in both normal and neoplastic transitional zone tissues. FOXA1 levels correlated with higher pT stages and Gleason scores, as well as with androgen (AR) and estrogen receptor expression. Moreover, FOXA1 overexpression was associated with faster biochemical disease progression, which was pronounced in patients with low AR levels. Finally, siRNA-based knockdown of FOXA1 induced decreased cell proliferation and migration. Moreover, in vitro tumorigenicity was inducible by ARs only in the presence of FOXA1, substantiating a functional cooperation between FOXA1 and AR. In conclusion, FOXA1 expression is associated with tumor progression, dedifferentiation of prostate cancer cells, and poorer prognosis, as well as with cellular proliferation and migration and with AR signaling. These findings suggest FOXA1 overexpression as a novel mechanism inducing castration resistance in prostate cancer. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2017-06-01

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

  3. King's Health Partners' Prostate Cancer Biobank (KHP PCaBB).

    PubMed

    Saifuddin, S R; Devlies, W; Santaolalla, A; Cahill, F; George, G; Enting, D; Rudman, S; Cathcart, P; Challacombe, B; Dasgupta, P; Galustian, C; Chandra, A; Chowdhury, S; Gillett, C; Van Hemelrijck, M

    2017-11-22

    The KHP PCaBB was established in 2013 and recruits donors from the Urology or Oncology Departments at Guy's Hospital in London (UK). Prostate cancer patients may be approached to give their consent for biobanking at any point in their treatment pathway, which allows residual material from their earlier diagnosis to be transferred and used by the Biobank. Currently, patients are specifically asked to donate samples of blood and surplus prostate tissue as well as permitting access to their clinical and pathological data that continues to be added throughout the course of their disease. Between 2013 and 2015, 549 prostate cancer patients gave their consent to the biobank and, the tissue repository collected 489 blood samples, 120 frozen prostate tissue samples and 1064 formalin fixed paraffin embedded diagnostic blocks.Prostate cancer has become a chronic disease in a large proportion of men, with many men receiving multiple subsequent treatments, and their treatment trajectory often spanning over decades. Therefore, this resource aims to provide an ideal research platform to explore potential variations in treatment response as well as disease markers in the different risk categories for prostate cancer.A recent audit of the KHP PCaBB revealed that between 2013 and 2015, 1796 patients were diagnosed with prostate cancer at King's Health Partners (KHP), out of which 549 (30.6%) gave their consent to KHP PCaBB. Comparisons between demographic and clinical characteristics of patients who had consented compared to the total patient population revealed that the KHP PCaBB is demographically representative of the total prostate cancer patient population seen in Guy's and St Thomas' NHS Foundation Trust (GSTT). We observed no differences in distribution of ethnicity (p = 0.507) and socioeconomic status (p = 0.097). Some differences were observed in clinical characteristics, specifically with treatment type - which differed significantly between the patients who had

  4. Circadian Genes and Risk for Prostate Cancer

    DTIC Science & Technology

    2009-03-01

    a randomized placebo-controlled clinical trial to determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer... finasteride  (an inhibitor of androgen bioactivation) could  prevent prostate cancer. Included in our study are approximately 1,800 case‐control pairs

  5. Genome-wide DNA methylation measurements in prostate tissues uncovers novel prostate cancer diagnostic biomarkers and transcription factor binding patterns.

    PubMed

    Kirby, Marie K; Ramaker, Ryne C; Roberts, Brian S; Lasseigne, Brittany N; Gunther, David S; Burwell, Todd C; Davis, Nicholas S; Gulzar, Zulfiqar G; Absher, Devin M; Cooper, Sara J; Brooks, James D; Myers, Richard M

    2017-04-17

    Current diagnostic tools for prostate cancer lack specificity and sensitivity for detecting very early lesions. DNA methylation is a stable genomic modification that is detectable in peripheral patient fluids such as urine and blood plasma that could serve as a non-invasive diagnostic biomarker for prostate cancer. We measured genome-wide DNA methylation patterns in 73 clinically annotated fresh-frozen prostate cancers and 63 benign-adjacent prostate tissues using the Illumina Infinium HumanMethylation450 BeadChip array. We overlaid the most significantly differentially methylated sites in the genome with transcription factor binding sites measured by the Encyclopedia of DNA Elements consortium. We used logistic regression and receiver operating characteristic curves to assess the performance of candidate diagnostic models. We identified methylation patterns that have a high predictive power for distinguishing malignant prostate tissue from benign-adjacent prostate tissue, and these methylation signatures were validated using data from The Cancer Genome Atlas Project. Furthermore, by overlaying ENCODE transcription factor binding data, we observed an enrichment of enhancer of zeste homolog 2 binding in gene regulatory regions with higher DNA methylation in malignant prostate tissues. DNA methylation patterns are greatly altered in prostate cancer tissue in comparison to benign-adjacent tissue. We have discovered patterns of DNA methylation marks that can distinguish prostate cancers with high specificity and sensitivity in multiple patient tissue cohorts, and we have identified transcription factors binding in these differentially methylated regions that may play important roles in prostate cancer development.

  6. Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015

    PubMed Central

    Gillessen, S.; Omlin, A.; Attard, G.; de Bono, J. S.; Efstathiou, E.; Fizazi, K.; Halabi, S.; Nelson, P. S.; Sartor, O.; Smith, M. R.; Soule, H. R.; Akaza, H.; Beer, T. M.; Beltran, H.; Chinnaiyan, A. M.; Daugaard, G.; Davis, I. D.; De Santis, M.; Drake, C. G.; Eeles, R. A.; Fanti, S.; Gleave, M. E.; Heidenreich, A.; Hussain, M.; James, N. D.; Lecouvet, F. E.; Logothetis, C. J.; Mastris, K.; Nilsson, S.; Oh, W. K.; Olmos, D.; Padhani, A. R.; Parker, C.; Rubin, M. A.; Schalken, J. A.; Scher, H. I.; Sella, A.; Shore, N. D.; Small, E. J.; Sternberg, C. N.; Suzuki, H.; Sweeney, C. J.; Tannock, I. F.; Tombal, B.

    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, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged. PMID:26041764

  7. A basal stem cell signature identifies aggressive prostate cancer phenotypes

    PubMed Central

    Smith, Bryan A.; Sokolov, Artem; Uzunangelov, Vladislav; Baertsch, Robert; Newton, Yulia; Graim, Kiley; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M.; Witte, Owen N.

    2015-01-01

    Evidence from numerous cancers suggests that increased aggressiveness is accompanied by up-regulation of signaling pathways and acquisition of properties common to stem cells. It is unclear if different subtypes of late-stage cancer vary in stemness properties and whether or not these subtypes are transcriptionally similar to normal tissue stem cells. We report a gene signature specific for human prostate basal cells that is differentially enriched in various phenotypes of late-stage metastatic prostate cancer. We FACS-purified and transcriptionally profiled basal and luminal epithelial populations from the benign and cancerous regions of primary human prostates. High-throughput RNA sequencing showed the basal population to be defined by genes associated with stem cell signaling programs and invasiveness. Application of a 91-gene basal signature to gene expression datasets from patients with organ-confined or hormone-refractory metastatic prostate cancer revealed that metastatic small cell neuroendocrine carcinoma was molecularly more stem-like than either metastatic adenocarcinoma or organ-confined adenocarcinoma. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common between prostate small cell neuroendocrine carcinoma and primary prostate basal cells. Taken together, our data suggest that aggressive prostate cancer shares a conserved transcriptional program with normal adult prostate basal stem cells. PMID:26460041

  8. Estrogen and estrogen receptor alpha promotes malignancy and osteoblastic tumorigenesis in prostate cancer.

    PubMed

    Mishra, Sweta; Tai, Qin; Gu, Xiang; Schmitz, James; Poullard, Ashley; Fajardo, Roberto J; Mahalingam, Devalingam; Chen, Xiaodong; Zhu, Xueqiong; Sun, Lu-Zhe

    2015-12-29

    The role of estrogen signaling in regulating prostate tumorigenesis is relatively underexplored. Although, an increasing body of evidence has linked estrogen receptor beta (ERß) to prostate cancer, the function of estrogen receptor alpha (ERα) in prostate cancer is not very well studied. We have discovered a novel role of ERα in the pathogenesis of prostate tumors. Here, we show that prostate cancer cells express ERα and estrogen induces oncogenic properties in prostate cancer cells through ERα. Importantly, ERα knockdown in the human prostate cancer PacMetUT1 cells as well as pharmacological inhibition of ERα with ICI 182,780 inhibited osteoblastic lesion formation and lung metastasis in vivo. Co-culture of pre-osteoblasts with cancer cells showed a significant induction of osteogenic markers in the pre-osteoblasts, which was attenuated by knockdown of ERα in cancer cells suggesting that estrogen/ERα signaling promotes crosstalk between cancer and osteoblastic progenitors to stimulate osteoblastic tumorigenesis. These results suggest that ERα expression in prostate cancer cells is essential for osteoblastic lesion formation and lung metastasis. Thus, inhibition of ERα signaling in prostate cancer cells may be a novel therapeutic strategy to inhibit the osteoblastic lesion development as well as lung metastasis in patients with advanced prostate cancer.

  9. FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer

    PubMed Central

    Andren, Ove; Ohlson, Anna‐Lena; Carlsson, Jessica; Andersson, Swen‐Olof; Giunchi, Francesca; Rider, Jennifer R.; Fiorentino, Michelangelo

    2017-01-01

    Background The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (Tregs). In the present study we evaluated the prevalence of Treg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer. Methods Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4+ Tregs and CD8+ Tregs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of Tregs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area. Results In men with prostate cancer, similarly high numbers of stromal CD4+ Tregs were identified in PAH and tumor, but CD4+ Tregs were less common in PIN. Greater numbers of epithelial CD4+ Tregs in normal prostatic tissue were positively associated with both Gleason score and pT‐stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4+ Tregs in the normal prostatic tissue counterpart. Conclusions Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4+ Tregs and indicate that transformation of the anti‐tumor immune response may be initiated even before the primary tumor is established. PMID:29105795

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

    PubMed

    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 < 0.25). Patients with high tumor expression of chromatin-related genes had worse clinical characteristics (Gleason grade > 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.

  11. Bruton's tyrosine kinase is a potential therapeutic target in prostate cancer.

    PubMed

    Kokabee, Leila; Wang, Xianhui; Sevinsky, Christopher J; Wang, Wei Lin Winnie; Cheu, Lindsay; Chittur, Sridar V; Karimipoor, Morteza; Tenniswood, Martin; Conklin, Douglas S

    2015-01-01

    Bruton's tyrosine kinase (BTK) is a non-receptor tyrosine kinase that has mainly been studied in haematopoietic cells. We have investigated whether BTK is a potential therapeutic target in prostate cancer. We find that BTK is expressed in prostate cells, with the alternate BTK-C isoform predominantly expressed in prostate cancer cells and tumors. This isoform is transcribed from an alternative promoter and results in a protein with an amino-terminal extension. Prostate cancer cell lines and prostate tumors express more BTK-C transcript than the malignant NAMALWA B-cell line or human lymphomas. BTK protein expression is also observed in tumor tissue from prostate cancer patients. Down regulation of this protein with RNAi or inhibition with BTK-specific inhibitors, Ibrutinib, AVL-292 or CGI-1746 decrease cell survival and induce apoptosis in prostate cancer cells. Microarray results show that inhibiting BTK under these conditions increases expression of apoptosis related genes, while overexpression of BTK-C is associated with elevated expression of genes with functions related to cell adhesion, cytoskeletal structure and the extracellular matrix. These results are consistent with studies that show that BTK signaling is important for adhesion and migration of B cells and suggest that BTK-C may confer similar properties to prostate cancer cells. Since BTK-C is a survival factor for these cells, it represents both a potential biomarker and novel therapeutic target for prostate cancer.

  12. Body mass index and mortality in men with prostate cancer.

    PubMed

    Cantarutti, Anna; Bonn, Stephanie E; Adami, Hans-Olov; Grönberg, Henrik; Bellocco, Rino; Bälter, Katarina

    2015-08-01

    Body Mass index (BMI) has been shown to affect risk and mortality of several cancers. Prostate cancer and obesity are major public health concerns for middle-aged and older men. Previous studies of pre-diagnostic BMI have found an increased risk of prostate cancer mortality in obese patients. To study the associations between BMI at time of prostate cancer diagnosis and prostate cancer specific and overall mortality. BMI was analyzed both as a continuous variable and categorized into four groups based on the observed distribution in the cohort (BMI < 22.5, 22.5 < 25, 25 < 27.5 and ≥27.5 kg/m2). The association between BMI and mortality was assessed using stratified Cox proportional hazards models and by fitting regression splines for dose response analysis in 3,161 men diagnosed with prostate cancer. After 11 years of follow up via linkage to the population-based cause of death registry, we identified 1,161 (37%) deaths off which 690 (59%) were due to prostate cancer. High BMI (BMI ≥ 27.5 kg/m2) was associated with a statistically significant increased risk of prostate cancer specific mortality (HR:1.44, 95% CI: 1.09-1.90) and overall mortality (HR:1.33, 95% CI: 1.09-1.63) compared to the reference group (BMI 22.5 < 25 kg/m2). Additionally, men with a low BMI (<22.5 kg/m2 ), had a statistically significant increased risk of prostate cancer specific mortality (HR:1.33, 95% CI: 1.02-1.74) and overall mortality (HR:1.36, 95% CI: 1.11-1.67) compared to the reference. However, this effect disappeared when men who died within the first two years of follow-up were excluded from the analyses while the increased risk of prostate cancer specific mortality and overall mortality remained statistically significant for men with a BMI ≥ 27.5 kg/m2 (HR:1.44, 95% CI: 1.09-1.90 and HR: 1.33, 95% CI: 1.09-1.63, respectively). This study showed that a high BMI at time of prostate cancer diagnosis was associated with increased overall mortality

  13. Genetics of Prostate Cancer (PDQ®)—Health Professional Version

    Cancer.gov

    Familial prostate cancer is associated with certain inherited gene mutations (variants). Learn about the hereditary prostate cancer genes, genetic testing, clinical management, and psychosocial issues in this expert-reviewed summary.

  14. RB Loss Promotes Prostate Cancer Metastasis

    PubMed Central

    Thangavel, Chellappagounder; Boopathi, Ettickan; Liu, Yi; Haber, Alex; Ertel, Adam; Bhardwaj, Anshul; Addya, Sankar; Williams, Noelle; Ciment, Stephen J.; Cotzia, Paolo; Dean, Jeffry L.; Snook, Adam; McNair, Chris; Price, Matt; Hernandez, James R.; Zhao, Shuang G.; Birbe, Ruth; McCarthy, James B.; Turley, Eva A.; Pienta, Kenneth J.; Feng, Felix Y.; Dicker, Adam P.; Knudsen, Karen E.; Den, Robert B.

    2017-01-01

    RB loss occurs commonly in neoplasia but its contributions to advanced cancer have not been assessed directly. Here we show that RB loss in multiple murine models of cancer produces a prometastatic phenotype. Gene expression analyses showed that regulation of the cell motility receptor RHAMM by the RB/E2F pathway was critical for epithelial–mesenchymal transition, motility, and invasion by cancer cells. Genetic modulation or pharmacologic inhibition of RHAMM activity was sufficient and necessary for metastatic phenotypes induced by RB loss in prostate cancer. Mechanistic studies in this setting established that RHAMM stabilized F-actin polymerization by controlling ROCK signaling. Collectively, our findings show how RB loss drives metastatic capacity and highlight RHAMM as a candidate therapeutic target for treating advanced prostate cancer. PMID:27923835

  15. Drug discovery in prostate cancer mouse models.

    PubMed

    Valkenburg, Kenneth C; Pienta, Kenneth J

    2015-01-01

    The mouse is an important, though imperfect, organism with which to model human disease and to discover and test novel drugs in a preclinical setting. Many experimental strategies have been used to discover new biological and molecular targets in the mouse, with the hopes of translating these discoveries into novel drugs to treat prostate cancer in humans. Modeling prostate cancer in the mouse, however, has been challenging, and often drugs that work in mice have failed in human trials. The authors discuss the similarities and differences between mice and men; the types of mouse models that exist to model prostate cancer; practical questions one must ask when using a mouse as a model; and potential reasons that drugs do not often translate to humans. They also discuss the current value in using mouse models for drug discovery to treat prostate cancer and what needs are still unmet in field. With proper planning and following practical guidelines by the researcher, the mouse is a powerful experimental tool. The field lacks genetically engineered metastatic models, and xenograft models do not allow for the study of the immune system during the metastatic process. There remain several important limitations to discovering and testing novel drugs in mice for eventual human use, but these can often be overcome. Overall, mouse modeling is an essential part of prostate cancer research and drug discovery. Emerging technologies and better and ever-increasing forms of communication are moving the field in a hopeful direction.

  16. The biology and natural history of prostate cancer: a short introduction.

    PubMed

    Holmberg, Lars; Van Hemelrijck, Mieke

    2014-01-01

    This chapter aims to serve as a quick glance outlining an overall picture of mainstream thoughts, and to serve as a point of departure for more thorough discussions. The introduction of PSA testing has immensely complicated research in prostate cancer epidemiology and biology and added new clinical and biological domains. As for many cancers, age and ethnic origin are the strongest known risk factors. While migrant studies imply that environment and/or personal life style is important, epidemiological studies have failed to establish any strong leads. Despite the known androgen dependence of prostate cancer, there is little to support that circulating levels of androgens, estrogens or 5-alpha-reductase are associated with risk of developing the disease. However, a consistent finding is a positive association with levels of Insulin-like Growth Factor-1 (IGF-1). Prostate cancer is one of the cancers most strongly related to inherited susceptibility, even when taking into account that family history of prostate cancer triggers PSA testing among relatives. A number of somatic genetic alterations (amplifications, deletions, point mutations, translocations) are associated with prostate cancer risk. Findings for alterations in FASN, HPN, AMACR and MYC have been fairly consistent. Recent research shows that the notion of "hormone-independent prostate cancer" has to be revised: most prostate cancers remain dependent on androgen receptor signalling also after progression despite traditional androgen deprivation therapy. Traditional markers of stage and type of disease still play a major role for prognostication and treatment decisions. Prostate cancer is one of the few cancers where patients have been recommended watchful waiting or active surveillance. This provides opportunities for studies of natural history of the disease. The understanding of prostate cancer aetiology and natural history has progressed slowly. However, the current situation is positively challenging and

  17. Hypofractionated Radiation Therapy in Treating Participants With Prostate Cancer High-Risk Features Following Radical Prostatectomy

    ClinicalTrials.gov

    2018-06-25

    Prostate Adenocarcinoma; PSA Level Less Than Two; Stage IIB Prostate Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8

  18. Cyclin-dependent kinase inhibitor, P276-00, inhibits HIF-1α and induces G2/M arrest under hypoxia in prostate cancer cells.

    PubMed

    Manohar, S M; Padgaonkar, A A; Jalota-Badhwar, A; Rao, S V; Joshi, K S

    2012-03-01

    Hypoxia-inducible factor-1 (HIF-1) is a master regulator of the transcriptional response to oxygen deprivation and controls genes involved in glycolysis, angiogenesis, migration and invasion. Overexpression of HIF-1α has been demonstrated in many common human cancers. Luciferase reporter gene assay under hypoxia and normoxia was used to demonstrate transcriptional inhibition of HIF-1 by P276-00. Detailed studies such as western blotting, reverse-transcriptase-PCR and immunofluorescence were carried out to elucidate its mechanism of action. Cytotoxic potential of P276-00 under normoxia and hypoxia was determined on prostate cancer cells using CCK-8 assay, and cell-cycle analysis was carried out using flow cytometry. Antiangiogenic activity of P276-00 was demonstrated by migration assay and tube-formation assay. Efficacy study of P276-00 was performed in a PC-3 xenograft model. P276-00 inhibits transcriptional activation of HIF-1 under hypoxia. It suppressed hypoxia-mediated nuclear HIF-1α expression, as well as phosphorylation of Akt and 4E-BP1 and abrogated expression of HIF-1-inducible gene viz. vascular endothelial growth factor. Under hypoxia, P276-00 did not exhibit enhanced cytotoxic activity in prostate cancer cells but arrested them in the G2/M phase of the cell cycle. The tubular formation of human umbilical vein endothelial cells and migration of prostate cancer cells were also inhibited by P276-00 in vitro. In addition, it demonstrated significant in vivo efficacy in the PC-3 xenograft model. Given its low toxicity profile, its demonstrated antitumor activity and its potential to inhibit the HIF-1 pathway, P276-00 should be considered as antiangiogenic chemotherapy for prostate cancer.

  19. A novel shape similarity based elastography system for prostate cancer assessment

    NASA Astrophysics Data System (ADS)

    Wang, Haisu; Mousavi, Seyed Reza; Samani, Abbas

    2012-03-01

    Prostate cancer is the second common cancer among men worldwide and remains the second leading cancer-related cause of death in mature men. The disease can be cured if it is detected at early stage. This implies that prostate cancer detection at early stage is very critical for desirable treatment outcome. Conventional techniques of prostate cancer screening and detection, such as Digital Rectal Examination (DRE), Prostate-Specific Antigen (PSA) and Trans Rectal Ultra-Sonography (TRUS), are known to have low sensitivity and specificity. Elastography is an imaging technique that uses tissue stiffness as contrast mechanism. As the association between the degree of prostate tissue stiffness alteration and its pathology is well established, elastography can potentially detect prostate cancer with a high degree of sensitivity and specificity. In this paper, we present a novel elastography technique which, unlike other elastography techniques, does not require displacement data acquisition system. This technique requires the prostate's pre-compression and postcompression transrectal ultrasound images. The conceptual foundation of reconstructing the prostate's normal and pathological tissues elastic moduli is to determine these moduli such that the similarity between calculated and observed shape features of the post compression prostate image is maximized. Results indicate that this technique is highly accurate and robust.

  20. Altered mitochondrial genome content signals worse pathology and prognosis in prostate cancer.

    PubMed

    Kalsbeek, Anton M F; Chan, Eva K F; Grogan, Judith; Petersen, Desiree C; Jaratlerdsiri, Weerachai; Gupta, Ruta; Lyons, Ruth J; Haynes, Anne-Maree; Horvath, Lisa G; Kench, James G; Stricker, Phillip D; Hayes, Vanessa M

    2018-01-01

    Mitochondrial genome (mtDNA) content is depleted in many cancers. In prostate cancer, there is intra-glandular as well as inter-patient mtDNA copy number variation. In this study, we determine if mtDNA content can be used as a predictor for prostate cancer staging and outcomes. Fresh prostate cancer biopsies from 115 patients were obtained at time of surgery. All cores underwent pathological review, followed by isolation of cancer and normal tissue. DNA was extracted and qPCR performed to quantify the total amount of mtDNA as a ratio to genomic DNA. Differences in mtDNA content were compared for prostate cancer pathology features and disease outcomes. We showed a significantly reduced mtDNA content in prostate cancer compared with normal adjacent prostate tissue (mean difference 1.73-fold, P-value <0.001). Prostate cancer with increased mtDNA content showed unfavorable pathologic characteristics including, higher disease stage (PT2 vs PT3 P-value = 0.018), extracapsular extension (P-value = 0.02) and a trend toward an increased Gleason score (P-value = 0.064). No significant association was observed between changes in mtDNA content and biochemical recurrence (median follow up of 107 months). Contrary to other cancer types, prostate cancer tissue shows no universally depleted mtDNA content. Rather, the change in mtDNA content is highly variable, mirroring known prostate cancer genome heterogeneity. Patients with high mtDNA content have an unfavorable pathology, while a high mtDNA content in normal adjacent prostate tissue is associated with worse prognosis. © 2017 Wiley Periodicals, Inc.

  1. Barriers and Facilitators of Prostate Cancer Screening among Filipino Men in Hawai’i

    PubMed Central

    Conde, Francisco A.; Landier, Wendy; Ishida, Dianne; Bell, Rose; Cuaresma, Charlene F.; Misola, Jane

    2013-01-01

    Purpose/Objectives To examine perceptions, attitudes, and beliefs regarding barriers and facilitators to prostate cancer screening, and to identify potential interventional strategies to promote prostate cancer screening among Filipino men in Hawai’i. Design Exploratory, qualitative. Setting Community-based settings in Hawai’i. Sample 20 Filipino men, 40 years old or older Methods Focus group discussions were tape-recorded, transcribed, and content analysis performed for emergent themes. Main Research Variables Perceptions regarding prostate cancer, barriers and facilitators to prostate cancer screening, and culturally-relevant interventional strategies Findings Perceptions of prostate cancer included fatalism, hopelessness, and dread. Misconceptions regarding causes of prostate cancer, such as frequency of sexual activity, were identified. Barriers to prostate cancer screening included lack of awareness of the need for screening, reticence to seek healthcare when feeling well, fear of cancer diagnosis, financial issues, time constraints, and embarrassment. Presence of urinary symptoms, personal experience with family or friend who had cancer, and receiving recommendations from a healthcare provider regarding screening were facilitators for screening. Potential culturally-relevant interventional strategies to promote prostate cancer screening included screening recommendations from health professionals and cancer survivors; radio/television commercials and newspaper articles targeted to the Filipino community; informational brochures in Tagalog, Ilocano and/or English; and interactive, educational forums facilitated by Filipino multilingual, male healthcare professionals. Conclusions Culturally-relevant interventions are needed that address barriers to prostate cancer screening participation and misconceptions about causes of prostate cancer. Implications for Nursing Findings provide a foundation for future research regarding development of interventional

  2. Cannabinoid Receptors: A Novel Target for Therapy for Prostate Cancer

    DTIC Science & Technology

    2008-02-01

    experiments, the long term implications of our study could be to develop nonhabit-forming cannabi - noid agonist (s) for the management of prostate cancer ...independent prostate cancer cell invasion. Cancer Res 2004;64:8826–30. 14. Sarfaraz S, Afaq F, Adhami VM, et al. Cannabi - noid receptors agonist WIN-55,212–2...for Therapy for Prostate Cancer PRINCIPAL INVESTIGATOR: Hasan Mukhtar, Ph.D. Farrukh Afaq, Ph.D. Sami Sarfaraz, Ph.D

  3. Vitamin D deficiency and insufficiency among patients with prostate cancer

    PubMed Central

    Trump, Donald L.; Chadha, Manpreet K.; Sunga, Annette Y.; Fakih, Marwan G.; Ashraf, Umeer; Silliman, Carrie G.; Hollis, Bruce W.; Nesline, Mary K.; Tian, Lili; Tan, Wei; Johnson, Candace S.

    2009-01-01

    Objective To assess the frequency of vitamin D deficiency among men with prostate cancer, as considerable epidemiological, in vitro, in vivo and clinical data support an association between vitamin D deficiency and prostate cancer outcome. Patients, subjects and methods The study included 120 ambulatory men with recurrent prostate cancer and 50 with clinically localized prostate cancer who were evaluated and serum samples assayed for 25-OH vitamin D levels. Then 100 controls (both sexes), matched for age and season of serum sample, were chosen from a prospective serum banking protocol. The relationship between age, body mass index, disease stage, Eastern Cooperative Oncology Group performance status, season and previous therapy on vitamin D status were evaluated using univariate and multivariate analyses. Results The mean 25-OH vitamin D level was 25.9 ng/mL in those with recurrent disease, 27.5 ng/mL in men with clinically localized prostate cancer and 24.5 ng/mL in controls. The frequency of vitamin D deficiency (< 20 ng/mL) and insufficiency (20–31 ng/mL) was 40% and 32% in men with recurrent prostate; 28% had vitamin D levels that were normal (32–100 ng/mL). Among men with localized prostate cancer, 18% were deficient, 50% were insufficient and 32% were normal. Among controls, 31% were deficient, 40% were insufficient and 29% were normal. Metastatic disease (P = 0.005) and season of blood sampling (winter/spring; P = 0.01) were associated with vitamin D deficiency in patients with prostate cancer, while age, race, performance status and body mass index were not. Conclusions Vitamin D deficiency and insufficiency were common among men with prostate cancer and apparently normal controls in the western New York region. PMID:19426195

  4. Unemployment and prostate cancer mortality in the OECD, 1990–2009

    PubMed Central

    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. PMID:26045715

  5. Immunohistochemical expression of interleukin-2 receptor and interleukin-6 in patients with prostate cancer and benign prostatic hyperplasia: association with asymptomatic inflammatory prostatitis NIH category IV.

    PubMed

    Engelhardt, Paul Friedrich; Seklehner, Stephan; Brustmann, Hermann; Lusuardi, Lukas; Riedl, Claus R

    2015-04-01

    This study prospectively investigated the immunohistochemical expression of interleukin-2 receptor (IL-2R) and interleukin-6 (IL-6) in patients with prostate cancer and benign prostatic hyperplasia (BPH), and a possible association of these conditions with asymptomatic inflammatory prostatitis National Institutes of Health (NIH) category IV. The study included 139 consecutive patients who underwent transurethral resection of the prostate and transvesical enucleation of the prostate (n = 82) or radical prostatectomy (n = 57). To characterize inflammatory changes the criteria proposed by Irani et al. [J Urol 1997;157:1301-3] were used. IL-2R and IL-6 expression was studied by a standard immunohistochemical method. Results were correlated with tumour, node, metastasis stage, Gleason scores, total prostate-specific antigen, International Prostate Symptom Score and body mass index. IL-2R and IL-6 expression was significantly higher in neoplastic prostate cancer tissue than in normal tissue of prostate cancer patients (p < 0.001 and p < 0.04, respectively). Prostate cancer patients with prostatitis showed significantly higher IL-2R expression than those without inflammation (p < 0.03). In patients with BPH, expression of IL-2R as well as IL-6 was higher in patients with prostatitis than in those without (p < 0.01 and p < 0.02, respectively). IL-2R and IL-6 expression was significantly higher in prostate cancer tissue than in normal tissue. Patients with asymptomatic inflammatory prostatitis NIH category IV showed significantly greater activity.

  6. The Future of Prostate Cancer Research and Treatment

    Cancer.gov

    On January 12, 2017 prostate cancer experts William Dahut, M.D. of the National Cancer Institute and Dr. Heather Cheng, M.D. of the University of Washington had a vibrant discussion about current and future research areas and treatment options for prostate cancer. The panel was moderated by Ana Fadich, MPH, CHES Vice President at Men’s Health of the Men's Health Network.

  7. The androgen receptor malignancy shift in prostate cancer.

    PubMed

    Copeland, Ben T; Pal, Sumanta K; Bolton, Eric C; Jones, Jeremy O

    2018-05-01

    Androgens and the androgen receptor (AR) are necessary for the development, function, and homeostatic growth regulation of the prostate gland. However, once prostate cells are transformed, the AR is necessary for the proliferation and survival of the malignant cells. This change in AR function appears to occur in nearly every prostate cancer. We have termed this the AR malignancy shift. In this review, we summarize the current knowledge of the AR malignancy shift, including the DNA-binding patterns that define the shift, the transcriptome changes associated with the shift, the putative drivers of the shift, and its clinical implications. In benign prostate epithelial cells, the AR primarily binds consensus AR binding sites. In carcinoma cells, the AR cistrome is dramatically altered, as the AR associates with FOXA1 and HOXB13 motifs, among others. This shift leads to the transcription of genes associated with a malignant phenotype. In model systems, some mutations commonly found in localized prostate cancer can alter the AR cistrome, consistent with the AR malignancy shift. Current evidence suggests that the AR malignancy shift is necessary but not sufficient for transformation of prostate epithelial cells. Reinterpretation of prostate cancer genomic classification systems in light of the AR malignancy shift may improve our ability to predict clinical outcomes and treat patients appropriately. Identifying and targeting the molecular factors that contribute to the AR malignancy shift is not trivial but by doing so, we may be able to develop new strategies for the treatment or prevention of prostate cancer. © 2018 Wiley Periodicals, Inc.

  8. Dissecting the roles of the androgen receptor in prostate cancer from molecular perspectives.

    PubMed

    Hu, Jieping; Wang, Gongxian; Sun, Ting

    2017-05-01

    Androgen receptor plays a pivotal role in prostate cancer progression, and androgen deprivation therapy to intercept androgen receptor signal pathway is an indispensable treatment for most advanced prostate cancer patients to delay cancer progression. However, the emerging of castration-resistant prostate cancer reminds us the alteration of androgen receptor, which includes androgen receptor mutation, the formation of androgen receptor variants, and androgen receptor distribution in cancer cells. In this review, we introduce the process of androgen receptor and also its variants' formation, translocation, and function alteration by protein modification or interaction with other pathways. We dissect the roles of androgen receptor in prostate cancer from molecular perspective to provide clues for battling prostate cancer, especially castration-resistant prostate cancer.

  9. Prediction of Erectile Function Following Treatment for Prostate Cancer

    PubMed Central

    Alemozaffar, Mehrdad; Regan, Meredith M.; Cooperberg, Matthew R.; Wei, John T.; Michalski, Jeff M.; Sandler, Howard M.; Hembroff, Larry; Sadetsky, Natalia; Saigal, Christopher S.; Litwin, Mark S.; Klein, Eric; Kibel, Adam S.; Hamstra, Daniel A.; Pisters, Louis L.; Kuban, Deborah A.; Kaplan, Irving D.; Wood, David P.; Ciezki, Jay; Dunn, Rodney L.; Carroll, Peter R.; Sanda, Martin G.

    2013-01-01

    Context Sexual function is the health-related quality of life (HRQOL) domain most commonly impaired after prostate cancer treatment; however, validated tools to enable personalized prediction of erectile dysfunction after prostate cancer treatment are lacking. Objective To predict long-term erectile function following prostate cancer treatment based on individual patient and treatment characteristics. Design Pretreatment patient characteristics, sexual HRQOL, and treatment details measured in a longitudinal academic multicenter cohort (Prostate Cancer Outcomes and Satisfaction With Treatment Quality Assessment; enrolled from 2003 through 2006), were used to develop models predicting erectile function 2 years after treatment. A community-based cohort (community-based Cancer of the Prostate Strategic Urologic Research Endeavor [CaPSURE]; enrolled 1995 through 2007) externally validated model performance. Patients in US academic and community-based practices whose HRQOL was measured pretreatment (N = 1201) underwent follow-up after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer. Sexual outcomes among men completing 2 years’ follow-up (n = 1027) were used to develop models predicting erectile function that were externally validated among 1913 patients in a community-based cohort. Main Outcome Measures Patient-reported functional erections suitable for intercourse 2 years following prostate cancer treatment. Results Two years after prostate cancer treatment, 368 (37% [95% CI, 34%–40%]) of all patients and 335 (48% [95% CI, 45%–52%]) of those with functional erections prior to treatment reported functional erections; 531 (53% [95% CI, 50%–56%]) of patients without penile prostheses reported use of medications or other devices for erectile dysfunction. Pretreatment sexual HRQOL score, age, serum prostate-specific antigen level, race/ethnicity, body mass index, and intended treatment details were associated with functional erections 2

  10. Inhibition of microRNA-500 has anti-cancer effect through its conditional downstream target of TFPI in human prostate cancer.

    PubMed

    Cai, Bing; Chen, Wei; Pan, Yue; Chen, Hongde; Zhang, Yirong; Weng, Zhiliang; Li, Yeping

    2017-07-01

    We investigated the prognostic potential and regulatory mechanism of microRNA-500 (miR-500), and human gene of tissue factor pathway inhibitor (TFPI) in prostate cancer. MiR-500 expression was assessed by qRT-PCR in prostate cancer cell lines and primary tumors. Cancer patients' clinicopathological factors and overall survival were analyzed according to endogenous miR-500 level. MiR-500 was downregulated in DU145 and VCaP cells. Its effect on prostate cancer proliferation, invasion in vitro, and tumorigenicity in vivo, were probed. Possible downstream target of miR-500, TFPI was assessed by luciferase assay and qRT-PCR in prostate cancer cells. In miR-500-downregulated DU145 and VCaP cells, TFPI was silenced to see whether it was directly involved in the regulation of miR-500 in prostate cancer. TFPI alone was either upregulated or downregulated in DU145 and VCaP cells. Their effect on prostate cancer development was further evaluated. MiR-500 is upregulated in both prostate cancer cells and primary tumors. In prostate cancer patients, high miR-500 expression is associated with poor prognosis and overall survival. In DU145 and VCaP cells, miR-500 downregulation inhibited cancer proliferation, invasion in vitro, and explant growth in vivo. TFPI was verified to be associated with miR-500 in prostate cancer. Downregulation of TFPI reversed anti-cancer effects of miR-500 downregulation in prostate cancer cells. However, neither TFPI upregulation nor downregulation alone had any functional impact on prostate cancer development. MiR-500 may be a potential biomarker and molecular target in prostate cancer. TFPI may conditionally regulate prostate cancer in miR-500-downregualted prostate cancer cells. © 2017 Wiley Periodicals, Inc.

  11. Beta Catenin in Prostate Cancer Apoptosis

    DTIC Science & Technology

    2011-04-03

    understand their role in apoptosis. TRAIL-TZD studies also revealed that pretreatment with a pharmacological inhibitor of GSK3B (AR-A014418) can sensitize...cells potently to TRAIL-induced apoptosis in the absence of TZD. These suggested that the inhibition of GSK3B activity might be the major mechanism by...which TZD sensitizes prostate cancer cells towards TRAIL. GSK3B might thus represent a novel target for developing prostate cancer therapeutics. The in

  12. Beta Catenin in Prostate Cancer Apoptosis

    DTIC Science & Technology

    2014-04-01

    indicate that, Glycogen Synthase Kinase 3β (GSK3β) might be a key player in mediating this. GSK3β, a multifunctional serine/ threonine kinase regulates...for TRAIL-TZD-induced apoptosis in prostate cancer cells. AMPK is a family of serine/ threonine protein kinase and is highly conserved from yeast to...metabolic syndrome and Type 2 diabetes . We used C42-DN (stably overexpressing AMPK α1-dominant negative) and C42-EV (empty vector) prostate cancer cell

  13. Plasma cell-free DNA and its DNA integrity as biomarker to distinguish prostate cancer from benign prostatic hyperplasia in patients with increased serum prostate-specific antigen.

    PubMed

    Feng, Jiang; Gang, Feng; Li, Xiao; Jin, Tang; Houbao, Huang; Yu, Cao; Guorong, Li

    2013-08-01

    To investigate whether plasma cell-free DNA (cfDNA) or its integrity could differentiate prostate cancer from benign prostate hyperplasia (BPH) in patients with serum prostate-specific antigen (PSA) ≥ 4 ng/ml. Ninety-six patients with prostate cancer and 112 patients with BPH were enrolled. cfDNA levels in plasma before prostate biopsy were quantified by real-time PCR amplification of ALU gene (product size of 115 bp), and quantitative ratio of ALU (247 bp) to ALU (115 bp) reflected the integrity of cfDNA. In patients with serum PSA ≥ 4 ng/ml, there were significant differences in plasma cfDNA or its integrity between the patients with prostate cancer (19.74 ± 4.43, 0.34 ± 0.05) and patients with BPH (7.36 ± 1.58, 0.19 ± 0.03; P < 0.001, P < 0.001). Prostate cancer could be differentiated with a sensitivity of 73.2 % and a specificity of 72.7 % by cfDNA (AUC = 0.864). The integrity of cfDNA had a sensitivity of 81.7 % and a specificity of 78.8 % for the distinguishing prostate cancer from BPH (AUC = 0.910). cfDNA and its integrity could be applied to differentiate prostate cancer from BPH in patients with serum PSA ≥ 4 ng/ml.

  14. Probing the prostate tumour microenvironment II: Impact of hypoxia on a cell model of prostate cancer progression

    PubMed Central

    Tonry, Claire; Armstrong, John; Pennington, Stephen

    2017-01-01

    Approximately one in six men are diagnosed with Prostate Cancer every year in the Western world. Although it can be well managed and non-life threatening in the early stages, over time many patients cease to respond to treatment and develop castrate resistant prostate cancer (CRPC). CRPC represents a clinically challenging and lethal form of prostate cancer. Progression of CRPC is, in part, driven by the ability of cancer cells to alter their metabolic profile during the course of tumourgenesis and metastasis so that they can survive in oxygen and nutrient-poor environments and even withstand treatment. This work was carried out as a continuation of a study aimed towards gaining greater mechanistic understanding of how conditions within the tumour microenvironment impact on both androgen sensitive (LNCaP) and androgen independent (LNCaP-abl and LNCaP-abl-Hof) prostate cancer cell lines. Here we have applied technically robust and reproducible label-free liquid chromatography mass spectrometry analysis for comprehensive proteomic profiling of prostate cancer cell lines under hypoxic conditions. This led to the identification of over 4,000 proteins – one of the largest protein datasets for prostate cancer cell lines established to date. The biological and clinical significance of proteins showing a significant change in expression as result of hypoxic conditions was established. Novel, intuitive workflows were subsequently implemented to enable robust, reproducible and high throughput verification of selected proteins of interest. Overall, these data suggest that this strategy supports identification of protein biomarkers of prostate cancer progression and potential therapeutic targets for CRPC. PMID:28410543

  15. Development of South Australian-Victorian Prostate Cancer Health Outcomes Research Dataset.

    PubMed

    Ruseckaite, Rasa; Beckmann, Kerri; O'Callaghan, Michael; Roder, David; Moretti, Kim; Zalcberg, John; Millar, Jeremy; Evans, Sue

    2016-01-22

    Prostate cancer is the most commonly diagnosed and prevalent malignancy reported to Australian cancer registries, with numerous studies from single institutions summarizing patient outcomes at individual hospitals or States. In order to provide an overview of patterns of care of men with prostate cancer across multiple institutions in Australia, a specialized dataset was developed. This dataset, containing amalgamated data from South Australian and Victorian prostate cancer registries, is called the South Australian-Victorian Prostate Cancer Health Outcomes Research Dataset (SA-VIC PCHORD). A total of 13,598 de-identified records of men with prostate cancer diagnosed and consented between 2008 and 2013 in South Australia and Victoria were merged into the SA-VIC PCHORD. SA-VIC PCHORD contains detailed information about socio-demographic, diagnostic and treatment characteristics of patients with prostate cancer in South Australia and Victoria. Data from individual registries are available to researchers and can be accessed under individual data access policies in each State. The SA-VIC PCHORD will be used for numerous studies summarizing trends in diagnostic characteristics, survival and patterns of care in men with prostate cancer in Victoria and South Australia. It is expected that in the future the SA-VIC PCHORD will become a principal component of the recently developed bi-national Australian and New Zealand Prostate Cancer Outcomes Registry to collect and report patterns of care and standardised patient reported outcome measures of men nation-wide in Australia and New Zealand.

  16. Prognostic Significance of Digital Rectal Examination and Prostate Specific Antigen in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Arm.

    PubMed

    Halpern, Joshua A; Shoag, Jonathan E; Mittal, Sameer; Oromendia, Clara; Ballman, Karla V; Hershman, Dawn L; Wright, Jason D; Shih, Ya-Chen Tina; Nguyen, Paul L; Hu, Jim C

    2017-02-01

    The absence of definitive data or explicit guidelines regarding the use of digital rectal examination for prostate cancer screening may lead to confusion for physicians and patients alike. We evaluated the prognostic value of abnormal digital rectal examination and prostate specific antigen following the widespread dissemination of prostate specific antigen testing in the U.S. Collectively, men comprising the screening arm of the PLCO cancer screening trial who underwent digital rectal examination screening (35,350) were followed for 314,033 person-years. Adjusted analyses with competing risks regression were performed to assess the association of suspicious (nodularity, induration, asymmetry) digital rectal examination and abnormal prostate specific antigen (4 ng/ml or greater) with the detection of clinically significant prostate cancer, prostate cancer specific mortality and overall mortality. Among all screening encounters with a suspicious digital rectal examination only 15.4% had a concurrently abnormal prostate specific antigen (McNemar's test p <0.001). During followup there were 1,612 clinically significant prostate cancers detected, 64 prostate cancer specific deaths and 4,600 deaths. On multivariable analysis suspicious digital rectal examination and abnormal prostate specific antigen were associated with a greater risk of clinically significant prostate cancer (HR 2.21, 95% CI 1.99-2.44 vs HR 5.48, 95% CI 5.05-5.96, p <0.001 and p <0.001) and prostate cancer specific mortality (HR 2.54, 95% CI 1.41-4.58 vs HR 5.23, 95% CI 3.08-8.88, p=0.002 and p <0.001), respectively. In a secondary analysis of a contemporary U.S. cohort, suspicious digital rectal examination and abnormal prostate specific antigen on routine screening were independently associated with clinically significant prostate cancer and prostate cancer specific mortality. However, additional research is needed to optimize screening protocols. Copyright © 2017 American Urological

  17. Collaborative Undergraduate HBCU Student Summer Prostate Cancer Training Program

    DTIC Science & Technology

    2010-03-01

    of prostate cancer among community members, and tips for preparing graduate school applications. Disparities research was a cross-cutting theme in...Prostate Cancer Research: Perspectives of Community Members HCC Cancer Disparities Board Members and Jim Etheredge, MPA Coordinator, HCC Cancer... Community Coalitions to Combat Health Disparities Mr. David Rivers, Director of Public Information and Community Outreach and Research Associate

  18. Concepts of epigenetics in prostate cancer development.

    PubMed

    Cooper, C S; Foster, C S

    2009-01-27

    Substantial evidence now supports the view that epigenetic changes have a role in the development of human prostate cancer. Analyses of the patterns of epigenetic alteration are providing important insights into the origin of this disease and have identified specific alterations that may serve as useful diagnostic and prognostic biomarkers. Examination of cancer methylation patterns supports a stem cell origin of prostate cancer. It is well established that methylation of GSTpi is a marker of prostate cancer, and global patterns of histone marking appear to be linked to cancer prognosis with levels of acetylated histones H3K9, H3K18, and H4K12, and of dimethylated H4R3 and H3K4, dividing low-grade prostate cancer (Gleason 6 or less) into two prognostically separate groups. Elevated levels of several components of the polycomb group protein complex, EZH2, BMI1, and RING1, can also act as biomarkers of poor clinical outcome. Many components of the epigenetic machinery, including histone deacetylase (whose expression level is linked to the TMPRSS2:ERG translocation) and the histone methylase EZH2, are potential therapeutic targets. The recent discovery of the role of small RNAs in governing the epigenetic status of individual genes offers exciting new possibilities in therapeutics and chemoprevention.

  19. Flavonoids and DNA Repair in Prostate Cancer

    DTIC Science & Technology

    2005-12-01

    1-0114 TITLE: Flavonoids and DNA Repair in Prostate Cancer...SUBTITLE Flavonoids and DNA Repair in Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-04-1-0114 5c. PROGRAM ELEMENT NUMBER...test the hypothesis that natural products such as flavonoids are able to stimulate the repair of oxidative DNA damage. For this purpose LNCaP

  20. Descriptive characteristics of prostate cancer in patients with a history of primary male breast cancer - a SEER analysis.

    PubMed

    Abhyankar, Nikita; Hoskins, Kent F; Abern, Michael R; Calip, Gregory S

    2017-09-25

    Current evidence on risk of prostate cancer following a diagnosis of male breast cancer is limited and guidance for screening in this potentially higher-risk population remainsunclear. Our objective was to quantify prostate cancer risk in men diagnosed with breast cancer. We identified men diagnosed with first primary breast cancer between 1988 and 2012 using the Surveillance, Epidemiology and End Results Program registry databases. Men were followed for occurrence of a second primary prostate cancer and secondary outcomes of cancer-specific and overall survival. Stratified analyses were performed by age, breast cancer stage, race, and breast cancer hormone receptor status. Excess risk per 10,000 person-years and standardized incidence ratios (SIR) with 95% confidence intervals (95% CI) were calculated. We used multivaraible Cox proportional hazard models to estimate hazard ratios (HR) and 95% CI for characteristics associated with secondary prostate cancer and survival. From a cohort of 5753 men with breast cancer with median follow up of 4.3 years, we identified 250 cases of second primary prostate cancer. Overall, the incidence of second primary prostate cancer was modestly greater than expected (SIR = 1.12, 95% CI 0.93-1.33), although not statistically significant. Stratified analyses demonstrated associations for men ages 65-74 at the time of breast cancer diagnosis (SIR = 1.34, 95%CI 1.01-1.73), hormone receptor-positive breast cancer (SIR = 1.23, 95%CI 1.11-1.39) or AJCC stage I breast cancer (SIR = 1.36, 95%CI 1.04-1.75) and second primary prostate cancer diagnosis. The incidence of prostate cancer in men with history of breast cancer is similar to the general population. Men with favorable characteristics of their breast cancer were more likely to develop prostate cancer, possibly due to a lower competing risk of breast cancer mortality.

  1. The emerging role of obesity, diet and lipid metabolism in prostate cancer.

    PubMed

    Ferro, Matteo; Terracciano, Daniela; Buonerba, Carlo; Lucarelli, Giuseppe; Bottero, Danilo; Perdonà, Sisto; Autorino, Riccardo; Serino, Alessandro; Cantiello, Francesco; Damiano, Rocco; Andras, Iulia; De Placido, Sabino; Di Lorenzo, Giuseppe; Battaglia, Michele; Jereczek-Fossa, Barbara A; Mirone, Vincenzo; De Cobelli, Ottavio

    2017-02-01

    Obesity is associated with an increased risk of a number of serious medical conditions, including cancer. As far as prostate cancer is concerned, obesity is associated with an increased risk of high-grade tumors, which is possibly related to lower androgen levels. Diet may also affect prostate cancer risk since countries with a higher dietary fat intake also present higher prostate cancer mortality rates. Interestingly, prostate cancer is associated with a number of metabolic alterations that may provide valuable diagnostic and therapeutic targets. This review explores the available clinical as well as biological evidence supporting the relationship between obesity, diet, alteration in metabolic pathways and prostate cancer.

  2. Non-coding RNAs in Prostate Cancer: From Discovery to Clinical Applications.

    PubMed

    Ceder, Yvonne

    2016-01-01

    Prostate cancer is a heterogeneous disease for which the molecular mechanisms are still not fully elucidated. Prostate cancer research has traditionally focused on genomic and epigenetic alterations affecting the proteome, but over the last decade non-coding RNAs, especially microRNAs, have been recognized to play a key role in prostate cancer progression. A considerable number of individual microRNAs have been found to be deregulated in prostate cancer and their biological significance elucidated in functional studies. This review will delineate the current advances regarding the involvement of microRNAs and their targets in prostate cancer biology as well as their potential usage in the clinical management of the disease. The main focus will be on microRNAs contributing to initiation and progression of prostate cancer, including androgen signalling, cellular plasticity, stem cells biology and metastatic processes. To conclude, implications on potential future microRNA-based therapeutics based on the recent advances regarding the interplay between microRNAs and their targets are discussed.

  3. African and Afro-Caribbean men's experiences of prostate cancer.

    PubMed

    Anderson, Beverley; Marshall-Lucette, Sylvie

    It is well documented that prostate cancer presents a significant health problem for middle-aged and elderly men in the UK, with further evidence suggesting that the disease is more prevalent in men of African and Afro-Caribbean (AAC) ethnicity. There is also evidence that these men are diagnosed much later and that the disease is more aggressive than in Caucasian men. To explore AAC men's experiences of prostate cancer and their understanding of its associated risks. The purpose was to gain an insight from these men's perspectives and ascertain whether a more focused health promotion strategy, and specific UK-based research, was needed in this area. A purposive sample of seven AAC men was recruited from a hospital trust's patient list after gaining approval from a research ethics committee. In-depth face-to-face interviews were carried out and the transcripts analysed thematically. The four main themes that emerged were: disease-prompted awareness, checking up as a necessary evil, defining and constructing factors influencing prostate cancer screening uptake, and appraising perceived myths about prostate cancer through personal beliefs. Among this group of AAC men, socioeconomic status, such as education and professional background, were factors that influenced their level of awareness of prostate cancer and prompted their decisions to seek help. However, it is evident from these men's perspectives that a more specific health education strategy that promotes early detection and management, targeting AAC men, would help in demystifying prostate cancer and encourage them to seek help earlier. Further research studies and health education in prominent social outlets are recommended in increasing AAC men's awareness of prostate cancer and its associated risks.

  4. AEG-1 promoter-mediated imaging of prostate cancer

    PubMed Central

    Bhatnagar, Akrita; Wang, Yuchuan; Mease, Ronnie C.; Gabrielson, Matthew; Sysa, Polina; Minn, Il; Green, Gilbert; Simmons, Brian; Gabrielson, Kathleen; Sarkar, Siddik; Fisher, Paul B.; Pomper, Martin G.

    2014-01-01

    We describe a new imaging method for detecting prostate cancer, whether localized or disseminated and metastatic to soft tissues and bone. The method relies on the use of imaging reporter genes under the control of the promoter of AEG-1 (MTDH), which is selectively active only in malignant cells. Through systemic, nanoparticle-based delivery of the imaging construct, lesions can be identified through bioluminescence imaging and single photon emission-computed tomography in the PC3-ML murine model of prostate cancer at high sensitivity. This approach is applicable for the detection of prostate cancer metastases, including bone lesions for which there is no current reliable agent for non-invasive clinical imaging. Further, the approach compares favorably to accepted and emerging clinical standards, including positron emission tomography with [18F]fluorodeoxyglucose and [18F]sodium fluoride. Our results offer a preclinical proof of concept that rationalizes clinical evaluation in patients with advanced prostate cancer. PMID:25145668

  5. Mortality and prostate cancer risk in 19,598 men after surgery for benign prostatic hyperplasia.

    PubMed

    Holman, C D; Wisniewski, Z S; Semmens, J B; Rouse, I L; Bass, A J

    1999-07-01

    To examine postoperative mortality and prostate cancer risk after the first prostatectomy for benign prostatic hypertrophy over a 17-year period in a population-based cohort of men in Western Australia, using improved methods to adjust for comorbidity. The relative survival from death and prostate cancer incidence was calculated against the background population rates. The outcomes of transurethral resection of the prostate (TURP) and open prostatectomy (OP) were compared adjusting for calendar year, age, admission type and comorbidity using Cox regression. Fractional polynomials were used to take account of nonlinearity in confounder effects. At 10 years, the relative survival was 116.5% in TURP patients and 123.5% after OP. Adjusting only for confounding by age, calendar year and admission type, TURP had a higher mortality rate than OP (rate ratio, RR, 1. 20; 95% confidence interval 1.08-1.34). The RR fell to 1.10 (0.99-1. 23) after adjustment for comorbidity and to 1.07 (0.95-1.19) when accounting for nonlinearity. The relative survival from the incidence of prostate cancer at 10 years was 103.7% after TURP and 104.5% after OP. The RR adjusted for age and calendar year was 1.44 (0.94-2.21) for incidence and 1.37 (0.81-2.29) for prostate cancer mortality. There is at most a small and clinically unimportant excess mortality risk from TURP; any difference could be due to a protective effect of OP on the long-term risk of prostate cancer and a lower rate of repeat prostatectomy.

  6. Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study

    PubMed Central

    Brunner, Clair; Davies, Neil M.; Martin, Richard M.; Eeles, Rosalind; Easton, Doug; Kote‐Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A.; Schleutker, Johanna; Nordestgaard, Børge G.; Travis, Ruth C.; Neal, David; Donovan, Jenny; Hamdy, Freddie C.; Pashayan, Nora; Khaw, Kay‐Tee; Stanford, Janet L.; Blot, William J.; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S.; Cybulski, Cezary; Cannon‐Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R.; Pandha, Hardev

    2016-01-01

    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 study, we investigated the associations of genetic variants in alcohol‐metabolising genes with prostate cancer incidence and survival. We analysed data from 23,868 men with prostate cancer and 23,051 controls from 25 studies within the international PRACTICAL Consortium. Study‐specific associations of 68 single nucleotide polymorphisms (SNPs) in 8 alcohol‐metabolising genes (Alcohol Dehydrogenases (ADHs) and Aldehyde Dehydrogenases (ALDHs)) with prostate cancer diagnosis and prostate cancer‐specific mortality, by grade, were assessed using logistic and Cox regression models, respectively. The data across the 25 studies were meta‐analysed using fixed‐effect and random‐effects models. We found little evidence that variants in alcohol metabolising genes were associated with prostate cancer diagnosis. Four variants in two genes exceeded the multiple testing threshold for associations with prostate cancer mortality in fixed‐effect meta‐analyses. SNPs within ALDH1A2 associated with prostate cancer mortality were rs1441817 (fixed effects hazard ratio, HRfixed = 0.78; 95% confidence interval (95%CI):0.66,0.91; p values = 0.002); rs12910509, HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.003); and rs8041922 (HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HRfixed = 1.43; 95%CI:1.14,1.79; p values = 0.002) was associated with prostate cancer mortality in men with low‐grade prostate cancer. These results suggest that alcohol consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression. PMID:27643404

  7. The curative management of synchronous rectal and prostate cancer

    PubMed Central

    Kavanagh, Dara O; Martin, Joseph; Small, Cormac; Joyce, Myles R; Faul, Clare M; Kelly, Paul J; O'Riordain, Michael; Gillham, Charles M; Armstrong, John G; Salib, Osama; McNamara, Deborah A; McVey, Gerard; O'Neill, Brian D P

    2016-01-01

    Objective: Neoadjuvant “long-course” chemoradiation is considered a standard of care in locally advanced rectal cancer. In addition to prostatectomy, external beam radiotherapy and brachytherapy with or without androgen suppression (AS) are well established in prostate cancer management. A retrospective review of ten cases was completed to explore the feasibility and safety of applying these standards in patients with dual pathology. To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. Methods: Eligible patients had synchronous histologically proven locally advanced rectal cancer (defined as cT3-4Nx; cTxN1-2) and non-metastatic prostate cancer (pelvic nodal disease permissible). Curative treatment was delivered to both sites simultaneously. Follow-up was as per institutional guidelines. Acute and late toxicities were reviewed, and a literature search performed. Results: Pelvic external beam radiotherapy (RT) 45–50.4 Gy was delivered concurrent with 5-fluorouracil (5FU). Prostate total dose ranged from 70.0 to 79.2 Gy. No acute toxicities occurred, excluding AS-induced erectile dysfunction. Nine patients proceeded to surgery, and one was managed expectantly. Three relapsed with metastatic colorectal cancer, two with metastatic prostate cancer. Five patients have no evidence of recurrence, and four remain alive with metastatic disease. With a median follow-up of 2.2 years (range 1.2–6.3 years), two significant late toxicities occurred; G3 proctitis in a patient receiving palliative bevacizumab and a G3 anastomotic stricture precluding stoma reversal. Conclusion: Patients proceeding to synchronous radical treatment of both primary sites should receive 45–50.4 Gy pelvic RT with infusional 5FU. Prostate dose escalation should be given with due consideration to the potential impact of prostate cancer on patient survival, as increasing dose may result in significant late morbidity

  8. Prostate cancer incidence and agriculture practices in Georgia, 2000-2010.

    PubMed

    Welton, Michael; Robb, Sara W; Shen, Ye; Guillebeau, Paul; Vena, John

    2015-01-01

    Georgia has prostate cancer incidence rates consistently above the national average. A notable portion of Georgia's economy is rooted in agricultural production, and agricultural practices have been associated with an increased risk of prostate cancer. Statistical analyses considered county age-adjusted prostate cancer incidence rates as the outcome of interest and three agricultural variables (farmland as percent of county land, dollars spent per county acre on agriculture chemicals, and dollars spent per county acre on commercial fertilizers) as exposures of interest. Multivariate linear regression models analyzed for each separately. Data were obtained from National Cancer Institute Surveillance, Epidemiology and End Results (SEER) 2000-2010, United States Department of Agriculture (USDA) 1987 Agriculture Survey, and 2010 US Census. In counties with equal to or greater than Georgia counties' median percent African-American population (27%), dollars per acre spent on agriculture chemicals was significantly associated (P = 0.04) and dollars spent of commercial fertilizers was moderately associated (P = 0.07) with elevated prostate cancer incidence rates. There was no association between percent of county farmland and prostate cancer rates. This study identified associations between prostate cancer incidence rates, agriculture chemical expenditure, and commercial fertilizer expenditure in Georgia counties with a population comprised of more than 27% of African Americans.

  9. Motor vehicle manufacturing and prostate cancer.

    PubMed

    Brown, D A; Delzell, E

    2000-07-01

    The purpose of this investigation was to evaluate the relation between employment in motor vehicle manufacturing (MVM) and fatal prostate cancer. The study included 322 prostate cancer deaths occurring in 1973 through 1987 and 1,285 controls, selected from a cohort of 126,100 male MVM workers. Men employed in casting operations had an odds ratio of 1.5 (95% CI = 1. 1-2.0). The association was consistent across casting facilities and was attributable primarily to work in core and mold making (OR = 1.5, 95% CI = 1.1-2.2) and metal melting and pouring jobs (OR = 1.9, 95% CI = 1.0-3.6). Other results included ORs of 1.9 (95% CI = 1.0-3.7) for warehousing and distribution operations and 2.1 (95% CI = 1.2-3. 7) for electric and electronic equipment manufacturing. The latter two associations exhibited little internal consistency. The relationships seen in this study were weak and may have been due to chance. Core and mold making and metal melting and pouring foundry operations entail potential exposure to metal dusts and fumes, to polycyclic aromatic hydrocarbons (PAHs), and to other chemicals. However, associations between these exposures and prostate cancer have not been reported consistently, nor have other studies of foundry workers consistently noted an excess of prostate cancer. Copyright 2000 Wiley-Liss, Inc.

  10. Prostatic cancers: understanding their molecular pathology and the 2016 WHO classification

    PubMed Central

    Inamura, Kentaro

    2018-01-01

    Accumulating evidence suggests that prostatic cancers represent a group of histologically and molecularly heterogeneous diseases with variable clinical courses. In accordance with the increased knowledge of their clinicopathologies and genetics, the World Health Organization (WHO) classification of prostatic cancers has been revised. Additionally, recent data on their comprehensive molecular characterization have increased our understanding of the genomic basis of prostatic cancers and enabled us to classify them into subtypes with distinct molecular pathologies and clinical features. Our increased understanding of the molecular pathologies of prostatic cancers has permitted their evolution from a poorly understood, heterogeneous group of diseases with variable clinical courses to characteristic molecular subtypes that allow the implementation of personalized therapies and better patient management. This review provides perspectives on the new 2016 WHO classification of prostatic cancers as well as recent knowledge of their molecular pathologies. The WHO classification of prostatic cancers will require additional revisions to allow for reliable and clinically meaningful cancer diagnoses as a better understanding of their molecular characteristics is obtained. PMID:29581876

  11. Bruton's tyrosine kinase is a potential therapeutic target in prostate cancer

    PubMed Central

    Kokabee, Leila; Wang, Xianhui; Sevinsky, Christopher J; Wang, Wei Lin Winnie; Cheu, Lindsay; Chittur, Sridar V; Karimipoor, Morteza; Tenniswood, Martin; Conklin, Douglas S

    2015-01-01

    Bruton's tyrosine kinase (BTK) is a non-receptor tyrosine kinase that has mainly been studied in haematopoietic cells. We have investigated whether BTK is a potential therapeutic target in prostate cancer. We find that BTK is expressed in prostate cells, with the alternate BTK-C isoform predominantly expressed in prostate cancer cells and tumors. This isoform is transcribed from an alternative promoter and results in a protein with an amino-terminal extension. Prostate cancer cell lines and prostate tumors express more BTK-C transcript than the malignant NAMALWA B-cell line or human lymphomas. BTK protein expression is also observed in tumor tissue from prostate cancer patients. Down regulation of this protein with RNAi or inhibition with BTK-specific inhibitors, Ibrutinib, AVL-292 or CGI-1746 decrease cell survival and induce apoptosis in prostate cancer cells. Microarray results show that inhibiting BTK under these conditions increases expression of apoptosis related genes, while overexpression of BTK-C is associated with elevated expression of genes with functions related to cell adhesion, cytoskeletal structure and the extracellular matrix. These results are consistent with studies that show that BTK signaling is important for adhesion and migration of B cells and suggest that BTK-C may confer similar properties to prostate cancer cells. Since BTK-C is a survival factor for these cells, it represents both a potential biomarker and novel therapeutic target for prostate cancer. PMID:26383180

  12. Vasectomy and prostate cancer risk: a historical synopsis of undulating false causality.

    PubMed

    Nutt, Max; Reed, Zachary; Köhler, Tobias S

    2016-01-01

    The potential influence of vasectomy being a risk factor for the development of prostate cancer is not a new concept, with more than 30 publications addressing the topic. Given the global frequency of vasectomy and the prevalence of prostate cancer, this subject justifiably deserves scrutiny. Several articles have claimed that vasectomy puts men at risk for future development of prostate cancer. We explore articles that have shown the contrary (no link), explore the studies' strengths and weaknesses, describe possible prostate cancer pathophysiologic mechanisms, and apply Bradford Hill criteria to help discern correlation with causation. The risk and interest of association of prostate cancer with vasectomy has waxed and waned over the last three decades. Based on our review, vasectomy remains a safe form of sterilization and does not increase prostate cancer risk.

  13. Keratin 13 expression reprograms bone and brain metastases of human prostate cancer cells.

    PubMed

    Li, Qinlong; Yin, Lijuan; Jones, Lawrence W; Chu, Gina C-Y; Wu, Jason B-Y; Huang, Jen-Ming; Li, Quanlin; You, Sungyong; Kim, Jayoung; Lu, Yi-Tsung; Mrdenovic, Stefan; Wang, Ruoxiang; Freeman, Michael R; Garraway, Isla; Lewis, Michael S; Chung, Leland W K; Zhau, Haiyen E

    2016-12-20

    Lethal progression of prostate cancer metastasis can be improved by developing animal models that recapitulate the clinical conditions. We report here that cytokeratin 13 (KRT13), an intermediate filament protein, plays a directive role in prostate cancer bone, brain, and soft tissue metastases. KRT13 expression was elevated in bone, brain, and soft tissue metastatic prostate cancer cell lines and in primary and metastatic clinical prostate, lung, and breast cancer specimens. When KRT13 expression was determined at a single cell level in primary tumor tissues of 44 prostate cancer cases, KRT13 level predicted bone metastasis and the overall survival of prostate cancer patients. Genetically enforced KRT13 expression in human prostate cancer cell lines drove metastases toward mouse bone, brain and soft tissues through a RANKL-independent mechanism, as KRT13 altered the expression of genes associated with EMT, stemness, neuroendocrine/neuromimicry, osteomimicry, development, and extracellular matrices, but not receptor activator NF-κB ligand (RANKL) signaling networks in prostate cancer cells. Our results suggest new inhibitors targeting RANKL-independent pathways should be developed for the treatment of prostate cancer bone and soft tissue metastases.

  14. The Function of Neuroendocrine Cells in Prostate Cancer

    DTIC Science & Technology

    2015-06-20

    Comprehensive Cancer Center and 4Broad Center for Regenerative Medicine and Stem Cell Biology, David Geffen School of Medicine at UCLA, 10833 Le Conte... Regenerative Medicine and Stem Cell Research, UCLA David Geffen School of Medicine , Los Angeles, California. 2Department of Urology, The First...progress in prostate cancer. Soochou University Annual Translational Medicine Meeting, Suzhou, China, November 2013 21. Prostate Cancer Stem Cells

  15. Cell growth inhibition and apoptotic effects of a specific anti-RTFscFv antibody on prostate cancer, but not glioblastoma, cells

    PubMed Central

    Nejatollahi, Foroogh; Bayat, Payam; Moazen, Bahareh

    2017-01-01

    Background: Single chain antibody (scFv) has shown interesting results in cancer immunotargeting approaches, due to its advantages over monoclonal antibodies. Regeneration and tolerance factor (RTF) is one of the most important regulators of extracellular and intracellular pH in eukaryotic cells. In this study, the inhibitory effects of a specific anti-RTF scFv were investigated and compared between three types of prostate cancer and two types of glioblastoma cells.  Methods: A phage antibody display library of scFv was used to select specific scFvs against RTF using panning process. The reactivity of a selected scFv was assessed by phage ELISA. The anti-proliferative and apoptotic effects of the antibody on prostate cancer (PC-3, Du-145 and LNCaP) and glioblastoma (U-87 MG and A-172) cell lines were investigated by MTT and Annexin V/PI assays.  Results: A specific scFv with frequency 35% was selected against RTF epitope. This significantly inhibited the proliferation of the prostate cells after 24 h. The percentages of cell viability (using 1000 scFv/cell) were 52, 61 and 73% for PC-3, Du-145 and LNCaP cells, respectively, compared to untreated cells. The antibody (1000 scFv/cell) induced apoptosis at 50, 40 and 25% in PC-3, Du-145 and LNCaP cells, respectively. No growth inhibition and apoptotic induction was detected for U-87 and A172 glioblastoma cells.  Conclusions: Anti-RTFscFv significantly reduced the proliferation of the prostate cancer cells. The inhibition of cell growth and apoptotic induction effects in PC-3 cells were greater than Du-145 and LNCaP cells. This might be due to higher expression of RTF antigen in PC-3 cells and/or better accessibility of RTF to scFv antibody. The resistance of glioblastoma cells to anti-RTF scFv offers the existence of mechanism(s) that abrogate the inhibitory effect(s) of the antibody to RTF. The results suggest that the selected anti-RTF scFv antibody could be an effective new alternative for prostate cancer

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

    PubMed

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

    2016-02-01

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

  17. Molecular Validation of PACE4 as a Target in Prostate Cancer12

    PubMed Central

    D'Anjou, François; Routhier, Sophie; Perreault, Jean-Pierre; Latil, Alain; Bonnel, David; Fournier, Isabelle; Salzet, Michel; Day, Robert

    2011-01-01

    Prostate cancer remains the single most prevalent cancer in men. Standard therapies are still limited and include androgen ablation that initially causes tumor regression. However, tumor cells eventually relapse and develop into a hormone-refractory prostate cancer. One of the current challenges in this disease is to define new therapeutic targets, which have been virtually unchanged in the past 30 years. Recent studies have suggested that the family of enzymes known as the proprotein convertases (PCs) is involved in various types of cancers and their progression. The present study examined PC expression in prostate cancer and validates one PC, namely PACE4, as a target. The evidence includes the observed high expression of PACE4 in all different clinical stages of human prostate tumor tissues. Gene silencing studies targeting PACE4 in the DU145 prostate cancer cell line produced cells (cell line 4-2) with slower proliferation rates, reduced clonogenic activity, and inability to grow as xenografts in nude mice. Gene expression and proteomic profiling of the 4-2 cell line reveals an increased expression of known cancer-related genes (e.g., GJA1, CD44, IGFBP6) that are downregulated in prostate cancer. Similarly, cancer genes whose expression is decreased in the 4-2 cell line were upregulated in prostate cancer (e.g., MUC1, IL6). The direct role of PACE4 in prostate cancer is most likely through the upregulated processing of growth factors or through the aberrant processing of growth factors leading to sustained cancer progression, suggesting that PACE4 holds a central role in prostate cancer. PMID:21633671

  18. PREVALENCE OF BENIGN PROSTATIC HYPERPLASIA AND PROSTATE CANCER IN AFRICANS AND AFRICANS IN THE DIASPORA.

    PubMed

    Yeboah, E D

    2016-01-01

    There have been several publications on population or community prevalence of benign prostatic hyperplasia and prostate cancer from various countries and races but few reports are from Africa on Africans. A review on the prevalence of benign prostatic hyperplasia and prostate cancer in Africans and other races. The current literature on prevalence of benign prostatic hyperplasia (BPH), prostate cancer (PC), and benign prostatic hyperplasia co-existing with prostate cancer in Africans and other races is reviewed. Benign prostatic hyperplasia (BPH) prevalence in Ghana is responsible for 60% acute retention of urine and 28.6% of haematuria. Worldwide prevalence of BPH varies from 20 - 62% in men over 50 years and this includes USA, UK, Japan and Ghana. Reports from South Africa indicate prevalence of over 50% in adult males of 60 years. BPH co-existing with PC - Reports from USA, UK and Japan and Ghana reveal moderate association of BPH and PC. The co-existence of PC in patients being treated for BPH is 3 - 20% Prostate Cancer prevalence - There is high prevalence in USA, Scandinavian Countries, African Americans (AA) and Caribbean blacks. Ghana, Trinidad & Tobago have reported high prevalence of 6 -10% in men aged 50 years and above but others reported low prevalence in Africans from Africa. The low reporting from Africa of 10 - 40:100,000 is attributable to under reporting, absence of PSA screening/testing, lack of reliable cancer registries and poor medical facilities. Economic Costs of BPH and PC: BPH in the USA national direct costs are estimated at U$4Billion and individual costs of US$1536 annually. In Ghana, individual costs for BPH medications range from US$300 - 550 per year and cost for simple prostatectomy/TURP is estimated at US$1100. For prostate cancer, individual direct costs from Europe range from 6,575 - 12,000 euros, £2818.00 UK and over U$12,000 - 20,000 in USA per annum. In Ghana, individual direct costs ranges, for radical prostatectomy and

  19. Potential role of gastrointestinal microbiota composition in prostate cancer risk

    PubMed Central

    2013-01-01

    Background Among men in the U.S., prostate cancer is the most common cancer and the second leading cause of cancer death. Despite its prevalence, there are few established risk factors for prostate cancer. Some studies have found that intake of certain foods/nutrients may be associated with prostate cancer risk, but few have accounted for how intake and metabolic factors may interact to influence bioavailable nutrient levels and subsequent disease risk. Presentation of the hypothesis The composition of the gastrointestinal (GI) microbiome may influence metabolism of dietary compounds and nutrients (e.g., plant phenols, calcium, choline) that may be relevant to prostate cancer risk. We, therefore, propose the hypothesis that GI microbiota may have a markedly different composition among individuals with higher prostate cancer risk. These individuals could have microbial profiles that are conducive to intestinal inflammation and/or are less favorable for the metabolism and uptake of chemopreventive agents. Testing the hypothesis Because very little preliminary data exist on this potential association, a case–control study may provide valuable information on this topic. Such a study could evaluate whether the GI microbial profile is markedly different between three groups of individuals: healthy men, those with latent prostate cancer, and those with invasive prostate cancer. Any findings could then be validated in a larger study, designed to collect a series of specimens over time. Implications of the hypothesis Given the plethora of information emerging from the Human Microbiome Project, this is an opportune time to explore associations between the microbiome and complex human diseases. Identification of profiles that alter the host’s risk for disease may clarify inconsistencies in the literature on dietary factors and cancer risk, and could provide valuable targets for novel cancer prevention strategies. PMID:24180596

  20. Skp2 regulates androgen receptor through ubiquitin-mediated degradation independent of Akt/mTOR pathways in prostate cancer.

    PubMed

    Li, Bo; Lu, Wenfu; Yang, Qing; Yu, Xiuping; Matusik, Robert J; Chen, Zhenbang

    2014-04-01

    The intervention of advanced prostate cancer (PCa) in patients has been commonly depending on androgen deprivation therapy. Despite of tremendous research efforts, however, molecular mechanisms on AR regulation remain poorly understood, particularly for castration resistant prostate cancer (CRPC). Targeting AR and associated factors is considered an effective strategy in PCa treatment. Human prostate cancer cells were used in this study. Manipulations of Skp2 expression were achieved by Skp2 shRNA/siRNA or overexpression of plasmids. Dual luciferase reporter assay was applied for AR activity assessment. Western blot, ubiquitination assay, immunoprecipitation, and immunofluorescence were applied to detect the proteins. Our results demonstrated that Skp2 directly involves the regulation of AR expression through ubiquitination-mediated degradation. Skp2 interacted with AR protein in PCa cells, and enforced expression of Skp2 resulted in a decreased level and activity of AR. By contrast, Skp2 knockdown increased the protein accumulation and activity of AR. Importantly, changes of AR contributed by Skp2 led to subsequent alterations of PSA level in PCa cells. AR ubiquitination was significantly increased upon Skp2 overexpression but greatly reduced upon Skp2 knockdown. AR mutant at K847R abrogated Skp2-mediated ubiquitination of AR. NVP-BEZ235, a dual PI3K/mTOR inhibitor, remarkably inhibited Skp2 level with a striking elevation of AR. The results indicate that Skp2 is an E3 ligase for proteasome-dependent AR degradation, and K847 on AR is the recognition site for Skp2-mediated ubiquitination. Our findings reveal an essential role of Skp2 in AR signaling. © 2013 Wiley Periodicals, Inc.

  1. Combination therapy for biochemically recurrent prostate cancer tested in new trial | Center for Cancer Research

    Cancer.gov

    Prostate-specific antigen (PSA) is an enzyme released by the prostate gland and is found in abnormally high concentrations in the blood of men with prostate cancer. “Biochemical recurrence” is when PSA levels continue to rise after initial treatment for prostate cancer, such as surgery or radiation. Marijo Bilusic, M.D., of the Genitourinary Malignancies Branch is leading the

  2. Polyphenols and Prostate Cancer Chemoprevention

    DTIC Science & Technology

    2004-03-01

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

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

    PubMed

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

    2018-06-01

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

  4. Prostate Cancer Research Trial Helps John Spencer Treat His Cancer | NIH MedlinePlus the Magazine

    MedlinePlus

    ... turn Javascript on. Feature: Prostate Cancer Prostate Cancer Research Trial Helps John Spencer Treat His Cancer Past ... I moved to Chapel Hill in 1998. NIH Research to Results Immune Responses: Researchers at the National ...

  5. Cancer Localization in the Prostate with F-18 Fluorocholine Positron Emission Tomography

    DTIC Science & Technology

    2007-01-01

    INTRODUCTION Prostate cancer is the second leading cause of cancer death in American men over 50 years of age. Ultrasound - guided prostate biopsy is...currently the most common method for diagnosing and localizing cancer in the prostate. However, even when standard 6 or 12 needle biopsy templates... needles employed (1, 2). While progress has been made in the detection of primary prostate cancer using imaging techniques such as ultrasound and

  6. Prostate stromal cells express the progesterone receptor to control cancer cell mobility.

    PubMed

    Yu, Yue; Lee, Jennifer Suehyun; Xie, Ning; Li, Estelle; Hurtado-Coll, Antonio; Fazli, Ladan; Cox, Michael; Plymate, Stephen; Gleave, Martin; Dong, Xuesen

    2014-01-01

    Reciprocal interactions between epithelium and stroma play vital roles for prostate cancer development and progression. Enhanced secretions of cytokines and growth factors by cancer associated fibroblasts in prostate tumors create a favorable microenvironment for cancer cells to grow and metastasize. Our previous work showed that the progesterone receptor (PR) was expressed specifically in prostate stromal fibroblasts and smooth muscle cells. However, the expression levels of PR and its impact to tumor microenvironment in prostate tumors are poorly understood. Immunohistochemistry assays are applied to human prostate tissue biopsies. Cell migration, invasion and proliferation assays are performed using human prostate cells. Real-time PCR and ELISA are applied to measure gene expression at molecular levels. Immunohistochemistry assays showed that PR protein levels were decreased in cancer associated stroma when compared with paired normal prostate stroma. Using in vitro prostate stromal cell models, we showed that conditioned media collected from PR positive stromal cells inhibited prostate cancer cell migration and invasion, but had minor suppressive impacts on cancer cell proliferation. PR suppressed the secretion of stromal derived factor-1 (SDF-1) and interlukin-6 (IL-6) by stromal cells independent to PR ligands. Blocking PR expression by siRNA or supplementation of exogenous SDF-1 or IL-6 to conditioned media from PR positive stromal cells counteracted the inhibitory effects of PR to cancer cell migration and invasion. Decreased expression of the PR in cancer associated stroma may contribute to the elevated SDF-1 and IL-6 levels in prostate tumors and enhance prostate tumor progression.

  7. [Immunotherapy: a therapeutic revolution against prostate cancer?].

    PubMed

    Pracht, Marc; Herrera, Fernanda; Tawadros, Thomas; Berthold, Dominik

    2013-05-22

    The interaction between the immune system and cancer was an area of research interest for several decades. The recent U.S. Food and Drug Administration approval of sipuleucel-T and ipilimumab stimulated broader interest in manipulating immunity to fight cancer. In the context of prostate cancer, the immunotherapy strategies under development are therapeutic vaccination strategies, such as sipuleucel-T and PROSTVAC-VF, or immune checkpoint blockade of CTLA-4. Improved understanding of the immune responses generated by the development of predictive biomarkers for patient selection will guide rational combinations of these treatments and provide new treatment options in prostate cancer.

  8. Prostate Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing prostate cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  9. Prostate-specific Membrane Antigen PET: Clinical Utility in Prostate Cancer, Normal Patterns, Pearls, and Pitfalls.

    PubMed

    Hofman, Michael S; Hicks, Rodney J; Maurer, Tobias; Eiber, Matthias

    2018-01-01

    Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed in prostate cancer. Radiolabeled small molecules that bind with high affinity to its active extracellular center have emerged as a potential new diagnostic standard of reference for prostate cancer, resulting in images with extraordinary tumor-to-background contrast. Currently, gallium 68 ( 68 Ga)-PSMA-11 (or HBED-PSMA) is the most widely used radiotracer for PSMA positron emission tomography (PET)/computed tomography (CT) or PSMA PET/magnetic resonance (MR) imaging. Evolving evidence demonstrates superior sensitivity and specificity of PSMA PET compared to conventional imaging, with frequent identification of subcentimeter prostate cancer lesions. PSMA PET is effective for imaging disease in the prostate, lymph nodes, soft tissue, and bone in a "one-stop-shop" examination. There is emerging evidence for its clinical value in staging of high-risk primary prostate cancer and localization of disease in biochemical recurrence. The high sensitivity provided by PSMA PET, with frequent identification of small-volume disease, is redefining patterns of disease spread compared with those seen at conventional imaging. In metastatic castration-resistant prostate cancer, PSMA PET is frequently used for theranostic selection (eg, lutetium 177-PSMA radionuclide therapy), but its potential use for therapy monitoring is still under debate. However, evidence on its proper use to improve patient-related outcomes, particularly in the setting of early biochemical recurrence and targeted treatment of oligometastatic disease, is still missing. Despite the term prostate specific, PSMA functions as a folate hydrolase and is expressed in a range of normal tissues and in other benign and malignant processes. Knowledge of its physiologic distribution and other causes of uptake is essential to minimize false-positive imaging findings. © RSNA, 2018.

  10. CCL11 (eotaxin-1): a new diagnostic serum marker for prostate cancer.

    PubMed

    Agarwal, Manisha; He, Chang; Siddiqui, Javed; Wei, John T; Macoska, Jill A

    2013-05-01

    The recent recommendation of the U.S. Preventive Services Task Force against PSA-based screening for prostate cancer was based, in part, on the lack of demonstrated diagnostic utility of serum PSA values in the low, but detectable range to successfully predict prostate cancer. Though controversial, this recommendation reinforced the critical need to develop, validate, and determine the utility of other serum and/or urine transcript and protein markers as diagnostic markers for PCa. The studies described here were intended to determine whether inflammatory cytokines might augment serum PSA as a diagnostic marker for prostate cancer. Multiplex ELISA assays were performed to quantify CCL1, CCL2, CCL5, CCL8, CCL11, CCL17, CXCL1, CXCL5, CXCL8, CXCL10, CXCL12, and IL-6 protein levels in the serum of 272 men demonstrating serum PSA values of <10 ng/ml and undergoing a 12 core diagnostic needle biopsy for detection of prostate cancer. Logistic regression was used to identify the associations between specific chemokines and prostate cancer status adjusted for prostate volume, and baseline PSA. Serum levels for CCL1 (I-309) were significantly elevated among all men with enlarged prostates (P < 0.04). Serum levels for CCL11 (Eotaxin-1) were significantly elevated among men with prostate cancer regardless of prostate size (P < 0.01). The remaining 10 cytokines examined in this study did not exhibit significant correlations with either prostate volume or cancer status. Serum CCL11 values may provide a useful diagnostic tool to help distinguish between prostatic enlargement and prostate cancer among men demonstrating low, but detectable, serum PSA values. Copyright © 2012 Wiley Periodicals, Inc.

  11. CCL11 (Eotaxin-1): A New Diagnostic Serum Marker for Prostate Cancer

    PubMed Central

    Agarwal, Manisha; He, Chang; Siddiqui, Javed; Wei, John; Macoska, Jill A.

    2012-01-01

    Background The recent recommendation of the U.S. Preventive Services Task Force against PSA-based screening for prostate cancer was based, in part, on the lack of demonstrated diagnostic utility of serum PSA values in the low, but detectable range to successfully predict prostate cancer. Though controversial, this recommendation reinforced the critical need to develop, validate, and determine the utility of other serum and/or urine transcript and protein markers as diagnostic markers for PCa. The studies described here were intended to determine whether inflammatory cytokines might augment serum PSA as a diagnostic marker for prostate cancer. Methods Multiplex ELISA assays were performed to quantify CCL1, CCL2, CCL5, CCL8, CCL11, CCL17, CXCL1, CXCL5, CXCL8, CXCL10, CXCL12, and IL-6 protein levels in the serum of 272 men demonstrating serum PSA values of < 10 ng/ml and undergoing a 12 core diagnostic needle biopsy for detection of prostate cancer. Logistic regression was used to identify the associations between specific chemokines and prostate cancer status adjusted for prostate volume, and baseline PSA. Results Serum levels for CCL1 (I-309) were significantly elevated among all men with enlarged prostates (p<.04). Serum levels for CCL11 (Eotaxin-1) were significantly elevated among men with prostate cancer regardless of prostate size (p<.01). The remaining 10 cytokines examined in this study did not exhibit significant correlations with either prostate volume or cancer status. Conclusions Serum CCL11 values may provide a useful diagnostic tool to help distinguish between prostatic enlargement and prostate cancer among men demonstrating low, but detectable, serum PSA values. PMID:23059958

  12. Brachytherapy of prostate cancer after colectomy for colorectal cancer: pilot experience.

    PubMed

    Koutrouvelis, Panos G; Theodorescu, Dan; Katz, Stuart; Lailas, Niko; Hendricks, Fred

    2005-01-01

    We present a method of brachytherapy for prostate cancer using a 3-dimensional stereotactic system and computerized tomography guidance in patients without a rectum due to previous treatment for colorectal cancer. From June 1994 to November 2003 a cohort of 800 patients were treated with brachytherapy for prostate cancer. Four patients had previously been treated for colorectal cancer with 4,500 cGy external beam radiation therapy, abdominoperineal resection and chemotherapy, while 1 underwent abdominoperineal resection alone for ulcerative colitis. Because of previous radiation therapy, these patients were not candidates for salvage external beam radiation therapy or radical prostatectomy and they had no rectum for transrectal ultrasound guided transperineal brachytherapy or cryotherapy. A previously described, 3-dimensional stereotactic system was used for brachytherapy in these patients. The prescribed radiation dose was 120 to 144 Gy with iodine seeds in rapid strand format. Patient followup included clinical examination and serum prostate specific antigen measurement. Average followup was 18.6 months. Four patients had excellent biochemical control, while 1 had biochemical failure. Patients did not experience any gastrointestinal morbidity. One patient had a stricture of the distal ureter, requiring a stent. Three-dimensional computerized tomography guided brachytherapy for prostate cancer in patients with a history of colorectal cancer who have no rectum is a feasible method of treatment.

  13. Sequence variants of Toll-like receptor 4 and susceptibility to prostate cancer.

    PubMed

    Chen, Yen-Ching; Giovannucci, Edward; Lazarus, Ross; Kraft, Peter; Ketkar, Shamika; Hunter, David J

    2005-12-15

    Chronic inflammation has been hypothesized to be a risk factor for prostate cancer. The Toll-like receptor 4 (TLR4) presents the bacterial lipopolysaccharide (LPS), which interacts with ligand-binding protein and CD14 (LPS receptor) and activates expression of inflammatory genes through nuclear factor-kappaB and mitogen-activated protein kinase signaling. A previous case-control study found a modest association of a polymorphism in the TLR4 gene [11381G/C, GG versus GC/CC: odds ratio (OR), 1.26] with risk of prostate cancer. We assessed if sequence variants of TLR4 were associated with the risk of prostate cancer. In a nested case-control design within the Health Professionals Follow-up Study, we identified 700 participants with prostate cancer diagnosed after they had provided a blood specimen in 1993 and before January 2000. Controls were 700 age-matched men without prostate cancer who had had a prostate-specific antigen test after providing a blood specimen. We genotyped 16 common (>5%) single nucleotide polymorphisms (SNP) discovered in a resequencing study spanning TLR4 to test for association between sequence variation in TLR4 and prostate cancer. Homozygosity for the variant alleles of eight SNPs was associated with a statistically significantly lower risk of prostate cancer (TLR4_1893, TLR4_2032, TLR4_2437, TLR4_7764, TLR4_11912, TLR4_16649, TLR4_17050, and TLR4_17923), but the TLR4_15844 polymorphism corresponding to 11381G/C was not associated with prostate cancer (GG versus CG/CC: OR, 1.01; 95% confidence interval, 0.79-1.29). Six common haplotypes (cumulative frequency, 81%) were observed; the global test for association between haplotypes and prostate cancer was statistically significant (chi(2) = 14.8 on 6 degrees of freedom; P = 0.02). Two common haplotypes were statistically significantly associated with altered risk of prostate cancer. Inherited polymorphisms of the innate immune gene TLR4 are associated with risk of prostate cancer.

  14. Zinc Intake and Risk of Prostate Cancer: Case-Control Study and Meta-Analysis.

    PubMed

    Mahmoud, Abeer M; Al-Alem, Umaima; Dabbous, Firas; Ali, Mohamed M; Batai, Ken; Shah, Ebony; Kittles, Rick A

    2016-01-01

    Zinc is an essential dietary element that has been implicated in the pathogenesis of prostate cancer, a cancer that disproportionately affects men of African descent. Studies assessing the association of zinc intake and prostate cancer have yielded inconsistent results. Furthermore, very little is known about the relationship between zinc intake and prostate cancer among African Americans. We examined the association between self-reported zinc intake and prostate cancer in a hospital-based case-control study of African Americans. We then compared our results with previous studies by performing a meta-analysis to summarize the evidence regarding the association between zinc and prostate cancer. Newly diagnosed African American men with histologically confirmed prostate cancer (n = 127) and controls (n = 81) were recruited from an urban academic urology clinic in Washington, DC. Controls had higher zinc intake, with a mean of 14 mg/day versus 11 mg/day for cases. We observed a non-significant, non-linear increase in prostate cancer when comparing tertiles of zinc intake (OR <6.5 vs 6.5-12.5mg/day 1.8, 95% CI: 0.6,5.6; OR <6.5 vs >12.5mg/day 1.3, 95% CI: 0.2,6.5). The pooled estimate from 17 studies (including 3 cohorts, 2 nested case-control, 11 case-control studies, and 1 randomized clinical trial, with a total of 111,199 participants and 11,689 cases of prostate cancer) was 1.07hi vs lo 95% CI: 0.98-1.16. Using a dose-response meta-analysis, we observed a non-linear trend in the relationship between zinc intake and prostate cancer (p for nonlinearity = 0.0022). This is the first study to examine the relationship between zinc intake in black men and risk of prostate cancer and systematically evaluate available epidemiologic evidence about the magnitude of the relationship between zinc intake and prostate cancer. Despite of the lower intake of zinc by prostate cancer patients, our meta-analysis indicated that there is no evidence for an association between zinc

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

    PubMed

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

    2009-05-01

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

  16. Abiraterone for Hormone-Sensitive Prostate Cancers

    Cancer.gov

    An NCI Cancer Currents blog post on results from two clinical trials that showed adding abiraterone to androgen-deprivation therapy improved survival for men with metastatic hormone-sensitive prostate cancer.

  17. MD-miniRNA could be a more accurate biomarker for prostate cancer screening compared with serum prostate-specific antigen level.

    PubMed

    Xue, Dong; Zhou, Cui-Xing; Shi, Yun-Bo; Lu, Hao; He, Xiao-Zhou

    2015-05-01

    Prostate cancer and prostatic hyperplasia detection remains a great challenge, lacking of effective non-invasive and specific diagnostic biomarkers. In the current study, we aimed to identify the relative expression of plasma MD-miniRNA and its diagnostic performance in differentiating prostate cancer and prostatic hyperplasia patients from healthy controls, compared with serum prostate-specific antigen (PSA) level. All of the clinical participants (63 prostate cancer patients, 32 prostatic hyperplasia patients, and 50 healthy controls) were obtained from the Third Affiliated Hospital of Suzhou University in China between January 2013 and April 2014. Clinical characteristics were well matched. Plasma samples were extracted to test the relative expression of MD-miniRNA using the method of qRT-PCR. SPSS 22.0 statistical software package was used to analyze the data and GraphPad Prism 6.0 was used to generate the graphs. Relativity expression of plasma MD-miniRNA was significantly upregulated in prostate cancer, compared with prostatic hyperplasia patients and healthy controls. Serum PSA level revealed similar differences among these groups. MD-miniRNA presented a relatively high diagnostic accuracy with AUC of 0.86 (95 % CI 0.80-0.93) in differentiating prostate cancer patients from healthy controls. Simultaneously, MD-miniRNA was able to discriminate prostate cancer patients from prostatic hyperplasia controls with AUC of 0.79 (95 % CI 0.70-0.88). In addition, MD-miniRNA displayed a better diagnostic performance than PSA level. However, the panel of these two biomarkers revealed the best diagnostic performance, compared with either single biomarker. Results of this study showed that plasma MD-miniRNA could serve as a promising and noninvasive biomarker for diagnosing prostate cancer. Further large-scale studies are needed to confirm its clinical diagnosis accuracy.

  18. Choline intake and risk of lethal prostate cancer: incidence and survival123

    PubMed Central

    Richman, Erin L; Kenfield, Stacey A; Stampfer, Meir J; Giovannucci, Edward L; Zeisel, Steven H; Willett, Walter C; Chan, June M

    2012-01-01

    Background: Meat, milk, and eggs have been inconsistently associated with the risk of advanced prostate cancer. These foods are sources of choline—a nutrient that may affect prostate cancer progression through cell membrane function and one-carbon metabolism. No study has examined dietary choline and the risk of lethal prostate cancer. Objective: Our objective was to examine whether dietary choline, choline-containing compounds, and betaine (a choline metabolite) increase the risk of lethal prostate cancer. Design: We prospectively examined the intake of these nutrients and the risk of lethal prostate cancer among 47,896 men in the Health Professionals Follow-Up Study. In a case-only survival analysis, we examined the postdiagnostic intake of these nutrients and the risk of lethal prostate cancer among 4282 men with an initial diagnosis of nonmetastatic disease during follow-up. Diet was assessed with a validated questionnaire 6 times during 22 y of follow-up. Results: In the incidence analysis, we observed 695 lethal prostate cancers during 879,627 person-years. Men in the highest quintile of choline intake had a 70% increased risk of lethal prostate cancer (HR: 1.70; 95% CI: 1.18, 2.45; P-trend = 0.005). In the case-only survival analysis, we observed 271 lethal cases during 33,679 person-years. Postdiagnostic choline intake was not statistically significantly associated with the risk of lethal prostate cancer (HR for quintile 5 compared with quintile 1: 1.69; 95% CI: 0.93, 3.09; P-trend = 0.20). Conclusion: Of the 47,896 men in our study population, choline intake was associated with an increased risk of lethal prostate cancer. PMID:22952174

  19. Perspectives on the clinical development of immunotherapy in prostate cancer.

    PubMed

    Cordes, Lisa M; Gulley, James L; Madan, Ravi A

    2018-01-01

    Despite impressive survival benefits with immunotherapy in patients with various solid tumors, the full potential of these agents in prostate cancer has yet to be realized. Sipuleucel-T demonstrated a survival benefit in this population, indicating that prostate cancer is an immunoresponsive disease; however, these results have not been matched by other agents. A large trial with ipilimumab in prostate cancer failed to meet its primary objective, and small trials with PD-1/PD-L1 inhibitors did not yield a significant improvement in overall response. However, several late-stage clinical trials are underway with other vaccines in prostate cancer. Reports of clinical benefit with immunotherapies, particularly when used in combination or a select population, have provided the framework to develop sound clinical trials. Understanding immunogenic modulation, antigen spread, biomarkers, and DNA-repair defects will also help mold future strategies. Through rational patient selection and evidence-based combination approaches, patients with prostate cancer may soon derive durable survival benefits with immunotherapies.

  20. Contemporary results of focal therapy for prostate cancer using cryotherapy.

    PubMed

    Chalasani, V; Williams, A K; Chin, J

    2010-09-01

    With the increasing diagnosis of prostate cancer, there have been concerns expressed regarding the potential over-treatment that may ensue following the diagnosis of localized prostate cancer. Minimally invasive treatments such as cryotherapy have been used successfully to treat the entire gland, however complications such as incontinence and erectile dysfunction can still occur. Focal cryotherapy is a modification of the standard cryotherapy technique, aiming to only treat the portion of the prostate gland which has the cancer of clinical significance. The potential advantage of this is the minimization of complications; however the remainder of the prostate is still viable and so can develop cancer subsequently. There have been several published studies demonstrating promising efficacy with a low morbidity rate using focal cryotherapy to treat prostate cancer, however further follow up is required before definitive conclusions can be reached. The appropriate selection of patients and subsequent follow up are areas needing further research and the development of improved imaging modalities.