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Sample records for prostate cancer models

  1. Mouse Models of Prostate Cancer

    PubMed Central

    Valkenburg, Kenneth C.; Williams, Bart O.

    2011-01-01

    The development and optimization of high-throughput screening methods has identified a multitude of genetic changes associated with human disease. The use of immunodeficient and genetically engineered mouse models that mimic the human disease has been crucial in validating the importance of these genetic pathways in prostate cancer. These models provide a platform for finding novel therapies to treat human patients afflicted with prostate cancer as well as those who have debilitating bone metastases. In this paper, we focus on the historical development and phenotypic descriptions of mouse models used to study prostate cancer. We also comment on how closely each model recapitulates human prostate cancer. PMID:22111002

  2. 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.

  3. Prostate Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Prostate Cancer What is Prostate Cancer? How Tumors Form The body is made up ... the Escape (Esc) button on your keyboard.) How Prostate Cancer Occurs Prostate cancer occurs when a tumor forms ...

  4. Tracking Origins of Prostate Cancer: An Innovative in Vivo Modeling

    DTIC Science & Technology

    2014-11-01

    could express specifically in prostate under PB- Cre4 control, and could label normal, hyperplasic, neoplastic and malignant carcinoma cells . More...propose to develop an innovative and hitherto not attempted in vivo prostate cancer model that will delineate the exact cell of origin through...different stages of prostate cancer development and progression. We propose to study possible cell (s) of origin for prostate cancer by combinatorial

  5. Prostate Cancer

    MedlinePlus

    Prostate cancer Overview Prostate cancer is cancer that occurs in the prostate — a small walnut-shaped gland in men that produces the seminal fluid that nourishes and transports sperm. Prostate cancer is one of the most common types of ...

  6. Prostate cancer

    SciTech Connect

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

    1987-01-01

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

  7. 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 ...

  8. Pre-clinical Orthotopic Murine Model of Human Prostate Cancer.

    PubMed

    Shahryari, Varahram; Nip, Hannah; Saini, Sharanjot; Dar, Altaf A; Yamamura, Soichiro; Mitsui, Yozo; Colden, Melissa; Bucay, Nathan; Tabatabai, Laura Z; Greene, Kirsten; Deng, Guoren; Tanaka, Yuichiro; Dahiya, Rajvir; Majid, Shahana

    2016-08-29

    To study the multifaceted biology of prostate cancer, pre-clinical in vivo models offer a range of options to uncover critical biological information about this disease. The human orthotopic prostate cancer xenograft mouse model provides a useful alternative approach for understanding the specific interactions between genetically and molecularly altered tumor cells, their organ microenvironment, and for evaluation of efficacy of therapeutic regimens. This is a well characterized model designed to study the molecular events of primary tumor development and it recapitulates the early events in the metastatic cascade prior to embolism and entry of tumor cells into the circulation. Thus it allows elucidation of molecular mechanisms underlying the initial phase of metastatic disease. In addition, this model can annotate drug targets of clinical relevance and is a valuable tool to study prostate cancer progression. In this manuscript we describe a detailed procedure to establish a human orthotopic prostate cancer xenograft mouse model.

  9. Mouse models for studying prostate cancer bone metastasis

    PubMed Central

    Dai, Jinlu; Hensel, Janine; Wang, Ning; Kruithof-de Julio, Marianna; Shiozawa, Yusuke

    2016-01-01

    Once tumor cells metastasize to the bone, the prognosis for prostate cancer patients is generally very poor. The mechanisms involved in bone metastasis, however, remain elusive, because of lack of relevant animal models. In this manuscript, we describe step-by-step protocols for the xenograft mouse models that are currently used for studying prostate cancer bone metastasis. The different routes of tumor inoculation (intraosseous, intracardiac, intravenous and orthotopic) presented are useful for exploring the biology of bone metastasis. PMID:26916039

  10. Prostate Cancer Screening

    MedlinePlus

    ... Genetics of Prostate Cancer Prostate Cancer Screening Research Prostate Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Prostate Cancer Key Points Prostate cancer is a disease in ...

  11. Model-supported virtual environment for prostate cancer pattern analysis

    NASA Astrophysics Data System (ADS)

    Yu, Ping; McClain, Maxine A.; Xuan, Jianhua; Wang, Yue J.; Sesterhenn, Isabell A.; Moul, Judd W.; Zhang, Wei; Mun, Seong K.

    1999-05-01

    As a step toward understanding complex spatial distribution patterns of prostate cancers, a 3D master model of the prostate, showing major anatomical structures and probability maps of the location of tumors, has been pilot developed. A virtual environment supported by the 3D master model and in vivo imaging features, will be used to evaluate, simulate, and optimize the image guided needle biopsy and radiation therapy, thus potentially improving the efficacy of prostate cancer diagnosis, staging, and treatment. A deformable graphics algorithm has been developed to reconstruct the graphics models from 200 serially sectioned whole mount radical prostatectomy specimens and to support computerized needle biopsy simulations. For the construction of a generic model, a principal-axes 3D registration technique has been developed. Simulated evaluation and real data experiment have shown the satisfactory performance of the method in constructing initial generic model with localized prostate cancer placement. For the construction of statistical model, a blended model registration technique is advanced to perform a non-linear warping of the individual model to the generic model so that the prostate cancer probability distribution maps can be accurately positioned. The method uses a spine- surface model and a linear elastic model to dynamically deform both the surface and volume where object re-slicing is required. For the interactive visualization of the 3D master model, four modes of data display are developed: (1) transparent rendering of the generic model, (2) overlaid rendering of cancer distributions, (3) stereo rendering, and (4) true volumetric display, and a model-to-image registration technique using synthetic image phantoms is under investigation. Preliminary results have shown that use of this master model allows correct understanding of prostate cancer distribution patterns and rational optimization of prostate biopsy and radiation therapy strategies.

  12. 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

  13. Statistical modeling and visualization of localized prostate cancer

    NASA Astrophysics Data System (ADS)

    Wang, Yue J.; Xuan, Jianhua; Sesterhenn, Isabell A.; Hayes, Wendelin S.; Ebert, David S.; Lynch, John H.; Mun, Seong K.

    1997-05-01

    In this paper, a statistically significant master model of localized prostate cancer is developed with pathologically- proven surgical specimens to spatially guide specific points in the biopsy technique for a higher rate of prostate cancer detection and the best possible representation of tumor grade and extension. Based on 200 surgical specimens of the prostates, we have developed a surface reconstruction technique to interactively visualize in the clinically significant objects of interest such as the prostate capsule, urethra, seminal vesicles, ejaculatory ducts and the different carcinomas, for each of these cases. In order to investigate the complex disease pattern including the tumor distribution, volume, and multicentricity, we created a statistically significant master model of localized prostate cancer by fusing these reconstructed computer models together, followed by a quantitative formulation of the 3D finite mixture distribution. Based on the reconstructed prostate capsule and internal structures, we have developed a technique to align all surgical specimens through elastic matching. By labeling the voxels of localized prostate cancer by '1' and the voxels of other internal structures by '0', we can generate a 3D binary image of the prostate that is simply a mutually exclusive random sampling of the underlying distribution f cancer to gram of localized prostate cancer characteristics. In order to quantify the key parameters such as distribution, multicentricity, and volume, we used a finite generalized Gaussian mixture to model the histogram, and estimate the parameter values through information theoretical criteria and a probabilistic self-organizing mixture. Utilizing minimally-immersive and stereoscopic interactive visualization, an augmented reality can be developed to allow the physician to virtually hold the master model in one hand and use the dominant hand to probe data values and perform a simulated needle biopsy. An adaptive self- organizing

  14. Validation of the prostate health index in a predictive model of prostate cancer.

    PubMed

    Sanchís-Bonet, A; Barrionuevo-González, M; Bajo-Chueca, A M; Pulido-Fonseca, L; Ortega-Polledo, L E; Tamayo-Ruiz, J C; Sánchez-Chapado, M

    2017-08-12

    To validate and analyse the clinical usefulness of a predictive model of prostate cancer that incorporates the biomarker «[-2] pro prostate-specific antigen» using the prostate health index (PHI) in decision making for performing prostate biopsies. We isolated serum from 197 men with an indication for prostate biopsy to determine the total prostate-specific antigen (tPSA), the free PSA fraction (fPSA) and the [-2] proPSA (p2PSA). The PHI was calculated as p2PSA/fPSA×√tPSA. We created 2 predictive models that incorporated clinical variables along with tPSA or PHI. The performance of PHI was assessed with a discriminant analysis using receiver operating characteristic curves, internal calibration and decision curves. The areas under the curve for the tPSA and PHI models were 0.71 and 0.85, respectively. The PHI model showed a better ability to discriminate and better calibration for predicting prostate cancer but not for predicting a Gleason score in the biopsy ≥7. The decision curves showed a greater net benefit with the PHI model for diagnosing prostate cancer when the probability threshold was 15-35% and greater savings (20%) in the number of biopsies. The incorporation of p2PSA through PHI in predictive models of prostate cancer improves the accuracy of the risk stratification and helps in the decision-making process for performing prostate biopsies. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Producing a Mouse Model to Explore the Linkages Between Tocopherol Biology and Prostate Cancer

    DTIC Science & Technology

    2005-07-01

    Edwards, Prostate cancer and supplementation with alpha-tocopherol and beta -carotene: incidence and mortality in a controlled trial. J Natl Cancer ...1-0153 TITLE: Producing a Mouse Model to Explore the Linkages Between Tocopherol Biology and Prostate Cancer ...TITLE AND SUBTITLE Producing a Mouse Model to Explore the Linkages Between Tocopherol 5a. CONTRACT NUMBER Biology and Prostate Cancer 5b. GRANT

  16. Selective detection of histologically aggressive prostate cancer: an Early Detection Research Network Prediction model to reduce unnecessary prostate biopsies with validation in the Prostate Cancer Prevention Trial.

    PubMed

    Williams, Stephen B; Salami, Simpa; Regan, Meredith M; Ankerst, Donna P; Wei, John T; Rubin, Mark A; Thompson, Ian M; Sanda, Martin G

    2012-05-15

    Limited survival benefit and excess treatment because of prostate-specific antigen (PSA) screening in randomized trials suggests a need for more restricted selection of prostate biopsy candidates by discerning risk of histologically aggressive versus indolent cancer before biopsy. Subjects undergoing first prostate biopsy enrolled in a multicenter, prospective cohort of the National Cancer Institute Early Detection Research Network (N = 635) were analyzed to develop a model for predicting histologically aggressive prostate cancers. The control arm of the Prostate Cancer Prevention Trial (N = 3833) was used to validate the generalization of the predictive model. The Early Detection Research Network cohort was comprised of men among whom 57% had no cancer, 14% had indolent cancer, and 29% had aggressive cancer. Age, body mass index, family history of prostate cancer, abnormal digital rectal examination (DRE), and PSA density (PSAD) were associated with aggressive cancer (all P < .001). The Early Detection Research Network model outperformed PSA alone in predicting aggressive cancer (area under the curve [AUC] = 0.81 vs 0.71, P < .01). Model validation in the Prostate Cancer Prevention Trial cohort accurately identified men at low (<10%) risk of aggressive cancer for whom biopsy could be averted (AUC = 0.78; 95% confidence interval, 0.75-0.80). Under criteria from the Early Detection Research Network model, prostate biopsy can be restricted to men with PSAD >0.1 ng/mL/cc or abnormal DRE. When PSAD is <0.1 ng/mL/cc, family history or obesity can identify biopsy candidates. A predictive model incorporating age, family history, obesity, PSAD, and DRE elucidates criteria whereby ¼ of prostate biopsies can be averted while retaining high sensitivity in detecting aggressive prostate cancer. Copyright © 2011 American Cancer Society.

  17. A partial differential equation model of metastasized prostatic cancer.

    PubMed

    Friedman, Avner; Jain, Harsh Vardhan

    2013-06-01

    Biochemically failing metastatic prostate cancer is typically treated with androgen ablation. However, due to the emergence of castration-resistant cells that can survive in low androgen concentrations, such therapy eventually fails. Here, we develop a partial differential equation model of the growth and response to treatment of prostate cancer that has metastasized to the bone. Existence and uniqueness results are derived for the resulting free boundary problem. In particular, existence and uniqueness of solutions for all time are proven for the radially symmetric case. Finally, numerical simulations of a tumor growing in 2-dimensions with radial symmetry are carried in order to evaluate the therapeutic potential of different treatment strategies. These simulations are able to reproduce a variety of clinically observed responses to treatment, and suggest treatment strategies that may result in tumor remission, underscoring our model's potential to make a significant contribution in the field of prostate cancer therapeutics.

  18. 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 ...

  19. An RBF-PSO based approach for modeling prostate cancer

    NASA Astrophysics Data System (ADS)

    Perracchione, Emma; Stura, Ilaria

    2016-06-01

    Prostate cancer is one of the most common cancers in men; it grows slowly and it could be diagnosed in an early stage by dosing the Prostate Specific Antigen (PSA). However, a relapse after the primary therapy could arise in 25 - 30% of cases and different growth characteristics of the new tumor are observed. In order to get a better understanding of the phenomenon, a two parameters growth model is considered. To estimate the parameters values identifying the disease risk level a novel approach, based on combining Particle Swarm Optimization (PSO) with meshfree interpolation methods, is proposed.

  20. [Prostate cancer].

    PubMed

    Bey, P; Beckendorf, V; Stinès, J

    2001-10-01

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

  1. Computational Models of Anti-VEGF Therapies in Prostate Cancer

    DTIC Science & Technology

    2014-06-01

    individualized prostate cancer whole-body multicompartment PK/PD models. Each dot represents one individual from the TCGA PrCa dataset. Red = tumor; blue...represents one individual from the TCGA PrCa dataset. Red = tumor; blue = normal. The same data is plotted in each column, sorted using the expression of

  2. Prostate cancer

    PubMed Central

    Mazhar, D; Waxman, J

    2002-01-01

    It is a paradigm in cancer treatment that early detection and treatment improves survival. However, although screening measures lead to a higher rate of detection, for small bulk localised prostate cancer it remains unclear whether early detection and early treatment will lead to an overall decrease in mortality. The management options include surveillance, radiotherapy, and radical prostatectomy but there is no evidence base to evaluate the benefits of each approach. Advanced prostate cancer is managed by hormonal therapy. There have been major changes in treatment over the last two decades with the use of more humane treatment and developments in both chemotherapy and radiation. In this article we review the natural history and management of prostate cancer. PMID:12415080

  3. Modeling prostate cancer in mice: something old, something new, something premalignant, something metastatic.

    PubMed

    Irshad, Shazia; Abate-Shen, Cory

    2013-06-01

    More than 15 years ago, the first generation of genetically engineered mouse (GEM) models of prostate cancer was introduced. These transgenic models utilized prostate-specific promoters to express SV40 oncogenes specifically in prostate epithelium. Since the description of these initial models, there have been a plethora of GEM models of prostate cancer representing various perturbations of oncogenes or tumor suppressors, either alone or in combination. This review describes these GEM models, focusing on their relevance for human prostate cancer and highlighting their strengths and limitations, as well as opportunities for the future.

  4. Iodine uptake and prostate cancer in the TRAMP mouse model.

    PubMed

    Olvera-Caltzontzin, Paloma; Delgado, Guadalupe; Aceves, Carmen; Anguiano, Brenda

    2013-11-08

    Iodine supplementation exerts antitumor effects in several types of cancer. Iodide (I⁻) and iodine (I₂) reduce cell proliferation and induce apoptosis in human prostate cancer cells (LNCaP and DU-145). Both chemical species decrease tumor growth in athymic mice xenografted with DU-145 cells. The aim of this study was to analyze the uptake and effects of iodine in a preclinical model of prostate cancer (transgenic adenocarcinoma of the mouse prostate [TRAMP] mice/SV40-TAG antigens), which develops cancer by 12 wks of age. ¹²⁵I⁻ and ¹²⁵I₂ uptake was analyzed in prostates from wild-type and TRAMP mice of 12 and 24 wks in the presence of perchlorate (inhibitor of the Na⁺/I⁻ symporter [NIS]). NIS expression was quantified by quantitative polymerase chain reaction (qPCR). Mice (6 wks old) were supplemented with 0.125 mg I⁻ plus 0.062 mg I₂/mouse/day for 12 or 24 wks. The weight of the genitourinary tract (GUT), the number of acini with lesions, cell proliferation (levels of proliferating cell nuclear antigen [PCNA] by immunohistochemistry), p53 and p21 expression (by qPCR) and apoptosis (relative amount of nucleosomes by enzyme-linked immunosorbent assay) were evaluated. In both age-groups, normal and tumoral prostates take up both forms of iodine, but only I⁻ uptake was blocked by perchlorate. Iodine supplementation prevented the overexpression of NIS in the TRAMP mice, but had no effect on the GUT weight, cell phenotype, proliferation or apoptosis. In TRAMP mice, iodine increased p53 expression but had no effect on p21 (a p53-dependent gene). Our data corroborate NIS involvement in I⁻ uptake and support the notion that another transporter mediates I₂ uptake. Iodine did not prevent cancer progression. This result could be explained by a strong inactivation of the p53 pathway by TAG antigens.

  5. Iodine Uptake and Prostate Cancer in the TRAMP Mouse Model

    PubMed Central

    Olvera-Caltzontzin, Paloma; Delgado, Guadalupe; Aceves, Carmen; Anguiano, Brenda

    2013-01-01

    Iodine supplementation exerts antitumor effects in several types of cancer. Iodide (I−) and iodine (I2) reduce cell proliferation and induce apoptosis in human prostate cancer cells (LNCaP and DU-145). Both chemical species decrease tumor growth in athymic mice xenografted with DU-145 cells. The aim of this study was to analyze the uptake and effects of iodine in a preclinical model of prostate cancer (transgenic adenocarcinoma of the mouse prostate [TRAMP] mice/SV40-TAG antigens), which develops cancer by 12 wks of age. 125I− and 125I2 uptake was analyzed in prostates from wild-type and TRAMP mice of 12 and 24 wks in the presence of perchlorate (inhibitor of the Na+/I− symporter [NIS]). NIS expression was quantified by quantitative polymerase chain reaction (qPCR). Mice (6 wks old) were supplemented with 0.125 mg I− plus 0.062 mg I2/mouse/day for 12 or 24 wks. The weight of the genitourinary tract (GUT), the number of acini with lesions, cell proliferation (levels of proliferating cell nuclear antigen [PCNA] by immunohistochemistry), p53 and p21 expression (by qPCR) and apoptosis (relative amount of nucleosomes by enzyme-linked immunosorbent assay) were evaluated. In both age-groups, normal and tumoral prostates take up both forms of iodine, but only I− uptake was blocked by perchlorate. Iodine supplementation prevented the overexpression of NIS in the TRAMP mice, but had no effect on the GUT weight, cell phenotype, proliferation or apoptosis. In TRAMP mice, iodine increased p53 expression but had no effect on p21 (a p53-dependent gene). Our data corroborate NIS involvement in I− uptake and support the notion that another transporter mediates I2 uptake. Iodine did not prevent cancer progression. This result could be explained by a strong inactivation of the p53 pathway by TAG antigens. PMID:24306422

  6. Development of Interpretable Predictive Models for BPH and Prostate Cancer.

    PubMed

    Bermejo, Pablo; Vivo, Alicia; Tárraga, Pedro J; Rodríguez-Montes, J A

    2015-01-01

    Traditional methods for deciding whether to recommend a patient for a prostate biopsy are based on cut-off levels of stand-alone markers such as prostate-specific antigen (PSA) or any of its derivatives. However, in the last decade we have seen the increasing use of predictive models that combine, in a non-linear manner, several predictives that are better able to predict prostate cancer (PC), but these fail to help the clinician to distinguish between PC and benign prostate hyperplasia (BPH) patients. We construct two new models that are capable of predicting both PC and BPH. An observational study was performed on 150 patients with PSA ≥3 ng/mL and age >50 years. We built a decision tree and a logistic regression model, validated with the leave-one-out methodology, in order to predict PC or BPH, or reject both. Statistical dependence with PC and BPH was found for prostate volume (P-value < 0.001), PSA (P-value < 0.001), international prostate symptom score (IPSS; P-value < 0.001), digital rectal examination (DRE; P-value < 0.001), age (P-value < 0.002), antecedents (P-value < 0.006), and meat consumption (P-value < 0.08). The two predictive models that were constructed selected a subset of these, namely, volume, PSA, DRE, and IPSS, obtaining an area under the ROC curve (AUC) between 72% and 80% for both PC and BPH prediction. PSA and volume together help to build predictive models that accurately distinguish among PC, BPH, and patients without any of these pathologies. Our decision tree and logistic regression models outperform the AUC obtained in the compared studies. Using these models as decision support, the number of unnecessary biopsies might be significantly reduced.

  7. Mechanisms of Radiosensitization by the Neurotensin Receptor Antagonist SR48692 in Prostate Cancer Models

    DTIC Science & Technology

    2009-04-01

    Neurotensin Receptor Antagonist SR48692 in Prostate Cancer Models PRINCIPAL INVESTIGATOR: Jaroslaw Dziegielewski, Ph.D...Receptor Antagonist 5a. CONTRACT NUMBER SR48692 in Prostate Cancer Models 5b. GRANT NUMBER W81XWH-08-1-0114 5c. PROGRAM ELEMENT NUMBER 6...neurotensin receptor by SR48692 drug could sensitize cancer cells to radiation. SR48692 activity was measured in PC3, C42 and LNCaP prostate cancer

  8. 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/prostatecancer/index National Cancer Institute -- www.cancer.gov/cancertopics/ ...

  9. Risks of Prostate Cancer Screening

    MedlinePlus

    ... Genetics of Prostate Cancer Prostate Cancer Screening Research Prostate Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Prostate Cancer Key Points Prostate cancer is a disease in ...

  10. 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 ...

  11. Canine prostate models in preclinical studies of minimally invasive interventions: part I, canine prostate anatomy and prostate cancer models

    PubMed Central

    Báez-Díaz, Claudia; Sánchez-Margallo, Francisco Miguel

    2017-01-01

    The high prevalence of prostate cancer (PCa) in elderly men and technical advances in early detection of localized PCa have led to continued efforts to develop new therapeutic options of minimally invasive nature in current urologic oncology community. Increasing newly emerging therapies are undergoing preclinical tests on the technical feasibility, efficacy and safety in animal experiments. The dog is an ideal large animal because of its similar anatomy to human and the capability allowing the use of the same medical devices applied in future clinical trials. Awareness of the local anatomy, microvascular structure, and histological features of the prostate in dogs is essential to experimental design and performance of the tested procedures and techniques. Although dogs with spontaneous PCa may be used in preclinical investigation, the low incidence and pathological features limit its utility. Alternatively, canine orthotopic PCa models have a great potential in preclinical research for this purpose. The goal of this review is to provide detailed anatomic and histological information of the canine prostate, outline the pathological and clinical characteristics of spontaneous PCa in dogs and discuss the current status of canine orthotopic PCa models. PMID:28725597

  12. Localized Prostate Cancer

    MedlinePlus

    ... a decision aid for men with clinically localized prostate cancer (available at http://effectivehealthcare.ahrq.gov/prostate_da) ... A Decision Aid for Men With Clinically Localized Prostate Cancer Page 1 of 24 Introduction Men with clinically ...

  13. A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk

    DTIC Science & Technology

    2016-10-01

    of this application is to model prostate epithelial cells to understand the molecular basis for the disparities in prostate cancer risk between...foreskin skin fibroblast-derived iPSC into cells with characteristics of prostate epithelium, 2) identify differences in gene expression and epigenetic...signatures between prostate epithelial cells derived from iPSC of Caucasian and African-American foreskin fibroblasts and 3) compare and establish

  14. Cholesterol and prostate cancer.

    PubMed

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

    2012-12-01

    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.

  15. Evaluation of models predicting insignificant prostate cancer to select men for active surveillance of prostate cancer.

    PubMed

    Wong, L M; Neal, D E; Finelli, A; Davis, S; Bonner, C; Kapoor, J; Trachtenberg, J; Thomas, B; Hovens, C M; Costello, A J; Corcoran, N M

    2015-06-01

    In an era of personalized medicine, individualized risk assessment using easily available tools on the internet and the literature are appealing. However, uninformed use by clinicians and the public raises potential problems. Herein, we assess the performance of published models to predict insignificant prostate cancer (PCa), using a multi-national low-risk population that may be considered for active surveillance (AS) based on contemporary practice. Data on men suitable for AS but undergoing upfront radical prostatectomy were pooled from three international academic institutions in Cambridge (UK), Toronto (Canada) and Melbourne (Australia). Four predictive models identified from literature review were assessed for their ability to predict the presence of four definitions of insignificant PCa. Evaluation was performed using area under the curve (AUC) of receiver operating characteristic curves and Brier scores for discrimination, calibration curves and decision curve analysis. A cohort of 460 men meeting the inclusion criteria of all four nomograms was identified. The highest AUCs calculated for any of the four models ranged from 0.618 to 0.664, suggesting weak positive discrimination at best. Models had best discriminative ability for a definition of insignificant disease characterized by organ-confined Gleason score ⩽6 with a total volume ⩽0.5 ml or 1.3 ml. Calibration plots showed moderate range of predictive ability for the Kattan model though this model did not perform well at decision curve analysis. External assessment of models predicting insignificant PCa showed moderate performance at best. Uninformed interpretation may cause undue anxiety or false reassurance and they should be used with caution.

  16. Efficacy of targeted AKT inhibition in genetically engineered mouse models of PTEN-deficient prostate cancer.

    PubMed

    De Velasco, Marco A; Kura, Yurie; Yoshikawa, Kazuhiro; Nishio, Kazuto; Davies, Barry R; Uemura, Hirotsugu

    2016-03-29

    The PI3K/AKT pathway is frequently altered in advanced human prostate cancer mainly through the loss of functional PTEN, and presents as potential target for personalized therapy. Our aim was to determine the therapeutic potential of the pan-AKT inhibitor, AZD5363, in PTEN-deficient prostate cancer. Here we used a genetically engineered mouse (GEM) model of PTEN-deficient prostate cancer to evaluate the in vivo pharmacodynamic and antitumor activity of AZD5363 in castration-naïve and castration-resistant prostate cancer. An additional GEM model, based on the concomitant inactivation of PTEN and Trp53 (P53), was established as an aggressive model of advanced prostate cancer and was used to further evaluate clinically relevant endpoints after treatment with AZD5363. In vivo pharmacodynamic studies demonstrated that AZD5363 effectively inhibited downstream targets of AKT. AZD5363 monotherapy significantly reduced growth of tumors in castration-naïve and castration-resistant models of PTEN-deficient prostate cancer. More importantly, AZD5363 significantly delayed tumor growth and improved overall survival and progression-free survival in PTEN/P53 double knockout mice. Our findings demonstrate that AZD5363 is effective against GEM models of PTEN-deficient prostate cancer and provide lines of evidence to support further investigation into the development of treatment strategies targeting AKT for the treatment of PTEN-deficient prostate cancer.

  17. A Mouse Model for Prostate Cancer

    DTIC Science & Technology

    2001-07-01

    were: monoclonal antibody against smooth muscle actin (Sigma); monoclonal antibody against cytokeratin 14 (Biogenex); monoclonal antibody against CD1O5...generally explain the tissue-specific phenotypes of cancers. 12 DOD Annual Report/DAMD17-00-1-0091 Cory Abate-Shen VI. References 1. Jacks, T., Tumor...Stein, S. Greenfield, N., Seidman, C.E., Seidman, J.G., and Abate-Shen, C. (1998). Haploinsufficiency of MSX1: A mechanism for selective tooth agenesis

  18. Tracking Origins of Prostate Cancer - An Innovative In Vivo Modeling

    DTIC Science & Technology

    2013-09-01

    cancer of men and the most common cancer overall (1). The cancer cells may metastasize from the prostate to other parts of the body, particularly the...Line 1017, 1018, 1021 and 1022 were lost due to infertility (no pup was born in all four breeding pairs, even though we keep female breeders young

  19. Zinc and prostatic cancer

    PubMed Central

    Song, Yang; Ho, Emily

    2014-01-01

    Purpose of review Aim to understand the connection between zinc and prostatic cancer, and to summarize the recent findings about the functions of zinc in the maintenance of prostate health. Recent findings Contradictory findings have been reported by epidemiologic studies examining the association between zinc intake and the risk of prostate cancer. However, a growing body of experimental evidence support that high zinc levels are essential for prostate health. The possible mechanisms include the effects of zinc on the inhibition of terminal oxidation, induction of mitochondrial apoptogenesis, and suppression of NFκB activity. The most recent finding is the effects of zinc in the maintenance of DNA integrity in normal prostate epithelial cells (PrEC) by modulating the expression and activity of DNA repair and damage response proteins, especially p53. Zinc depletion in PrEC increased p53 expression but compromised p53 DNA binding activity resulting an impaired DNA repair function. Moreover, recent findings support the role of zinc transporters as tumor suppressors in the prostate. Summary Future studies need to discover sensitive and specific zinc biomarkers and perform more in vivo studies on the effects of zinc on prostate functions in normal animals or prostate cancer models. PMID:19684515

  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. Anti-IL-20 Monoclonal Antibody Suppresses Prostate Cancer Growth and Bone Osteolysis in Murine Models

    PubMed Central

    Hsu, Yu-Hsiang; Wu, Cheng-Ying; Hsing, Chung-Hsi; Lai, Wei-Ting; Wu, Li-Wha; Chang, Ming-Shi

    2015-01-01

    Interleukin (IL)-20 is a proinflammatory cytokine in the IL–10 family. IL–20 is associated with tumor promotion in the pathogenesis of oral, bladder, and breast cancer. However, little is known about the role of IL–20 in prostate cancer. We hypothesize that IL–20 promotes the growth of prostate cancer cells. Immunohistochemical staining showed that IL–20 and its receptors were expressed in human PC–3 and LNCaP prostate cancer cell lines and in prostate tumor tissue from 40 patients. In vitro, IL–20 upregulated N-cadherin, STAT3, vimentin, fibronectin, RANKL, cathepsin G, and cathepsin K, and increased the migration and colony formation of prostate cancer cells via activated p38, ERK1/2, AKT, and NF-κB signals in PC–3 cells. We investigated the effects of anti-IL–20 monoclonal antibody 7E on prostate tumor growth in vivo using SCID mouse subcutaneous and intratibial xenograft tumor models. In vivo, 7E reduced tumor growth, suppressed tumor-mediated osteolysis, and protected bone mineral density after intratibial injection of prostate cancer cells. We conclude that IL–20 is involved in the cell migration, colony formation, and tumor-induced osteolysis of prostate cancer. Therefore, IL–20 might be a novel target for treating prostate cancer. PMID:26440411

  2. [Prostate cancer].

    PubMed

    Morote, Joan; Maldonado, Xavier; Morales-Bárrera, Rafael

    2016-02-05

    The Vall d'Hebron multidisciplinary prostate cancer (PC) team reviews recent advances in the management of this neoplasm. Screening studies with long follow-up show a reduction in mortality, whereas active surveillance is emerging as a therapeutic approach of non-aggressive cancers. New markers increase the specificity of PSA and also allow targeting suspected aggressive cancers. Multiparametric magnetic resonance (mMRI) has emerged as the most effective method in the selection of patients for biopsy and also for local tumor staging. The paradigm of random prostatic biopsy is changing through the fusion techniques that allow guiding ultrasonography-driven biopsy of suspicious areas detected in mMRI. Radical prostatectomy (RP) and radiotherapy (RT) are curative treatments of localized PC and both have experienced significant technological improvements. RP is highly effective and the incorporation of robotic surgery is reducing morbidity. Modern RT allows the possibility of high tumor dose with minimal adjacent dose reducing its toxicity. Androgen deprivation therapy with LHRH analogues remains the treatment of choice for advanced PC, but should be limited to this indication. The loss of bone mass and adverse metabolic effects increases the frequency of fractures and cardiovascular morbimortality. After castration resistance in metastatic disease, new hormone-based drugs have demonstrated efficacy even after chemotherapy resistance. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  3. What is Prostate Cancer?

    MedlinePlus

    ... their doctors even knew they had it. Possible pre-cancerous conditions of the prostate Some research suggests that prostate cancer starts out as a pre-cancerous condition, although this is not yet known ...

  4. The 2008 European School of Oncology inside track conference, "predictive modeling in prostate cancer".

    PubMed

    Valdagni, Riccardo; Scardino, Peter T; Denis, Louis

    2009-07-01

    The European School of Oncology (ESO) Inside Track Conference, "Predictive Modeling in Prostate Cancer," the first event ever dedicated to prediction in prostate cancer, was organized in collaboration with the Prostate Program of Milan National Cancer Institute and the American Italian Cancer Foundation in the wonderful scenario of the Excelsior Lido Hotel in Venice on April 17 through 19, 2008. More than 240 participants from 23 countries attended this 3-day conference, which convened an exceptional group of experts from all over the world whose presentations provided a framework for understanding the state of the art in predictive modeling of prostate cancer and displayed future research trends in the uro-oncologic community. Cancer 2009;115(13 suppl):3035-8. (c) 2009 American Cancer Society.

  5. MYC and Prostate Cancer

    PubMed Central

    Koh, Cheryl M.; Bieberich, Charles J.; Dang, Chi V.; Nelson, William G.; Yegnasubramanian, Srinivasan; De Marzo, Angelo M.

    2010-01-01

    Prostate cancer, the majority of which is adenocarcinoma, is the most common epithelial cancer affecting a majority of elderly men in Western nations. Its manifestation, however, varies from clinically asymptomatic insidious neoplasms that progress slowly and do not threaten life to one that is highly aggressive with a propensity for metastatic spread and lethality if not treated in time. A number of somatic genetic and epigenetic alterations occur in prostate cancer cells. Some of these changes, such as loss of the tumor suppressors PTEN and p53, are linked to disease progression. Others, such as ETS gene fusions, appear to be linked more with early phases of the disease, such as invasion. Alterations in chromosome 8q24 in the region of MYC have also been linked to disease aggressiveness for many years. However, a number of recent studies in human tissues have indicated that MYC appears to be activated at the earliest phases of prostate cancer (e.g., in tumor-initiating cells) in prostatic intraepithelial neoplasia, a key precursor lesion to invasive prostatic adenocarcinoma. The initiation and early progression of prostate cancer can be recapitulated in genetically engineered mouse models, permitting a richer understanding of the cause and effects of loss of tumor suppressors and activation of MYC. The combination of studies using human tissues and mouse models paints an emerging molecular picture of prostate cancer development and early progression. This picture reveals that MYC contributes to disease initiation and progression by stimulating an embryonic stem cell–like signature characterized by an enrichment of genes involved in ribosome biogenesis and by repressing differentiation. These insights pave the way to potential novel therapeutic concepts based on MYC biology. PMID:21779461

  6. Effects of dutasteride on prostate growth in the large probasin-large T antigen mouse model of prostate cancer.

    PubMed

    Shao, T C; Li, H; Ittmann, M; Cunningham, G R

    2007-10-01

    We evaluated the effects of dutasteride for preventing or delaying prostate growth and neoplastic changes in a transgenic model of prostate cancer. Large probasin-large T antigen mice were treated for 4 or 8 weeks with dutasteride. The prostate and seminal vesicles were compared with those from intact and castrated large probasin-large T antigen mice and WT mice. Dutasteride greatly decreased the transgene induced increase in prostate weight but castration caused greater reduction. Dutasteride inhibited type 1 and 2, 5alpha-reductase activities, decreased DNA and protein, and increased apoptotic bodies and TUNEL staining in the dorsolateral prostate. No evidence of poorly differentiated cancer was seen. Dutasteride did not decrease the weight of the androgen dependent levator ani or bulbocavernosus muscle. Dutasteride inhibited type 1 and 2, 5alpha-reductase activities, and decreased DNA and protein content of the dorsolateral prostate without affecting androgen responsive muscle weight in large probasin-large T antigen mice. These studies provide support for the hypothesis that a 5alpha-reductase inhibitor inhibits the initiation and/or progression of clinical prostate cancers.

  7. Testosterone Therapy and Prostate Cancer.

    PubMed

    Davidson, Emily; Morgentaler, Abraham

    2016-05-01

    Changes in understanding regarding the relationship of androgens and prostate cancer have led to changes in the use of testosterone therapy. The evidence supports a finite ability of androgens to stimulate prostate cancer growth, with a maximum achieved at low testosterone concentrations, called the saturation model. The saturation point corresponds with maximal androgenic stimulation at 250 ng/dL. Evidence is reviewed herein regarding the relationship of testosterone to prostate cancer and the relatively new practice of offering testosterone therapy to men with a history of prostate cancer. Although no prospective controlled trials have been performed, results have been reassuring.

  8. Prostate Cancer Skeletal Metastases: Pathobiology and Interventions

    DTIC Science & Technology

    2005-02-01

    in higher levels in prostate carcinoma than in benign prostatic hyperplasia [35, 36], and is found in human metastatic lesions in bone [37]. However...compared to normal controls, benign prostatic hyperplasia , prostatitis, and localized or recurrent disease. In an animal model, prostate tumor cells...Malakouti S, Antar S, Kukreja S. Enhanced expression of parathyroid hormone-related protein in prostate cancer as compared with benign prostatic hyperplasia . Hum

  9. Screening for Prostate Cancer

    MedlinePlus

    Understanding Task Force Recommendations Screening for Prostate Cancer The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation on Screening for Prostate Cancer . This recommendation is for ...

  10. Prostate Cancer FAQs

    MedlinePlus

    ... Coffey – Holden Prostate Cancer Academy Awards Challenge Awards Creativity Awards Young Investigator Awards Scientific Retreat – Meeting Agenda ... Retreat Coffey – Holden Prostate Cancer Academy Challenge Awards Creativity Awards Young Investigator Awards Featured Scientific Retreat – Meeting ...

  11. Prostate Cancer Symptoms

    MedlinePlus

    ... Coffey – Holden Prostate Cancer Academy Awards Challenge Awards Creativity Awards Young Investigator Awards Scientific Retreat – Meeting Agenda ... Retreat Coffey – Holden Prostate Cancer Academy Challenge Awards Creativity Awards Young Investigator Awards Featured Scientific Retreat – Meeting ...

  12. Cryotherapy for prostate cancer

    MedlinePlus

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

  13. Development of an orthotopic model of human metastatic prostate cancer in the NOD-SCIDγ mouse (Mus musculus) anterior prostate.

    PubMed

    Cifuentes, Federico F; Valenzuela, Rodrigo H; Contreras, Héctor R; Castellón, Enrique A

    2015-10-01

    Prostate cancer is one of the most prevalent oncological diseases in males worldwide, and the mortalities resulting from this type of cancer are mainly due to metastasis. The most common models for the study of metastasis are transgenic and immunocompromised mice, which enable the study of the metastatic process in a controlled way by the injection of prostate cancer cells into the mice. In the present study, NOD-SCIDγ mice were injected orthotopically with PC3 cells in the anterior prostate in order to establish a metastatic model. The results demonstrated the development and growth of a primary tumor that preceded the formation of micrometastases in the lung, liver and pancreas, followed by macrometastases in the liver. This model adequately represents the dynamics of the metastatic process, and may be useful for novel therapeutic assays and post-surgical relapse studies.

  14. Predicting Drug Response in Human Prostate Cancer from Preclinical Analysis of In Vivo Mouse Models.

    PubMed

    Mitrofanova, Antonina; Aytes, Alvaro; Zou, Min; Shen, Michael M; Abate-Shen, Cory; Califano, Andrea

    2015-09-29

    Although genetically engineered mouse (GEM) models are often used to evaluate cancer therapies, extrapolation of such preclinical data to human cancer can be challenging. Here, we introduce an approach that uses drug perturbation data from GEM models to predict drug efficacy in human cancer. Network-based analysis of expression profiles from in vivo treatment of GEM models identified drugs and drug combinations that inhibit the activity of FOXM1 and CENPF, which are master regulators of prostate cancer malignancy. Validation of mouse and human prostate cancer models confirmed the specificity and synergy of a predicted drug combination to abrogate FOXM1/CENPF activity and inhibit tumorigenicity. Network-based analysis of treatment signatures from GEM models identified treatment-responsive genes in human prostate cancer that are potential biomarkers of patient response. More generally, this approach allows systematic identification of drugs that inhibit tumor dependencies, thereby improving the utility of GEM models for prioritizing drugs for clinical evaluation.

  15. Prostate cancer as a model for tumour immunotherapy

    PubMed Central

    Drake, Charles G.

    2011-01-01

    Advances in basic immunology have led to an improved understanding of the interactions between the immune system and tumours, generating renewed interest in approaches that aim to treat cancer immunologically. As clinical and preclinical studies of tumour immunotherapy illustrate several immunological principles, a review of these data is broadly instructive and is particularly timely now that several agents are beginning to show evidence of efficacy. This is especially relevant in the case of prostate cancer, as recent approval of sipuleucel-T by the US Food and Drug Administration marks the first antigen-specific immunotherapy approved for cancer treatment. Although this Review focuses on immunotherapy for prostate cancer, the principles discussed are applicable to many tumour types, and the approaches discussed are highlighted in that context. PMID:20651745

  16. [Markers of prostate cancer stem cells: research advances].

    PubMed

    Wang, Shun-Qi; Huang, Sheng-Song

    2013-12-01

    Prostate cancer is one of the most seriously malignant diseases threatening men's health, and the mechanisms of its initiation and progression are not yet completely understood. Recent years have witnessed distinct advances in researches on prostate cancer stem cells in many aspects using different sources of materials, such as human prostate cancer tissues, human prostate cancer cell lines, and mouse models of prostate cancer. Prostate cancer stem cell study offers a new insight into the mechanisms of the initiation and progression of prostate cancer and contributes positively to its treatment. This article presents an overview on the prostate cancer stem cell markers utilized in the isolation and identification of prostate cancer stem cells.

  17. Is prostate cancer different in black men? Answers from 3 natural history models.

    PubMed

    Tsodikov, Alex; Gulati, Roman; de Carvalho, Tiago M; Heijnsdijk, Eveline A M; Hunter-Merrill, Rachel A; Mariotto, Angela B; de Koning, Harry J; Etzioni, Ruth

    2017-06-15

    Black men in the United States have substantially higher prostate cancer incidence rates than the general population. The extent to which this incidence disparity is because prostate cancer is more prevalent, more aggressive, and/or more frequently diagnosed in black men is unknown. The authors estimated 3 independently developed models of prostate cancer natural history in black men and in the general population using an updated reconstruction of prostate-specific antigen screening, based on the National Health Interview Survey in 2005 and on prostate cancer incidence data from the Surveillance, Epidemiology, and End Results program during 1975 through 2000. By using the estimated models, the natural history of prostate cancer was compared between black men and the general population. The models projected that from 30% to 43% (range across models) of black men develop preclinical prostate cancer by age 85 years, a risk that is (relatively) 28% to 56% higher than that in the general population. Among men who had preclinical disease onset, black men had a similar risk of diagnosis (range, 35%-49%) compared with the general population (32%-44%), but their risk of progression to metastatic disease by the time of diagnosis was from 44% to 75% higher than that in the general population. Prostate cancer incidence patterns implicate higher incidence of preclinical disease and higher risk of metastatic progression among black men. The findings suggest screening black men earlier than white men and support further research into the benefit-harm tradeoffs of more aggressive screening policies for black men. Cancer 2017;123:2312-2319. © 2017 American Cancer Society. © 2017 American Cancer Society.

  18. Hypofractionation for prostate cancer.

    PubMed

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

    2009-01-01

    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 alpha/beta ratio, than 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 alpha/beta 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 but 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.

  19. Probabilistic pairwise Markov models: application to prostate cancer detection

    NASA Astrophysics Data System (ADS)

    Monaco, James; Tomaszewski, John E.; Feldman, Michael D.; Moradi, Mehdi; Mousavi, Parvin; Boag, Alexander; Davidson, Chris; Abolmaesumi, Purang; Madabhushi, Anant

    2009-02-01

    Markov Random Fields (MRFs) provide a tractable means for incorporating contextual information into a Bayesian framework. This contextual information is modeled using multiple local conditional probability density functions (LCPDFs) which the MRF framework implicitly combines into a single joint probability density function (JPDF) that describes the entire system. However, only LCPDFs of certain functional forms are consistent, meaning they reconstitute a valid JPDF. These forms are specified by the Gibbs-Markov equivalence theorem which indicates that the JPDF, and hence the LCPDFs, should be representable as a product of potential functions (i.e. Gibbs distributions). Unfortunately, potential functions are mathematical abstractions that lack intuition; and consequently, constructing LCPDFs through their selection becomes an ad hoc procedure, usually resulting in generic and/or heuristic models. In this paper we demonstrate that under certain conditions the LCDPFs can be formulated in terms of quantities that are both meaningful and descriptive: probability distributions. Using probability distributions instead of potential functions enables us to construct consistent LCPDFs whose modeling capabilities are both more intuitive and expansive than typical MRF models. As an example, we compare the efficacy of our so-called probabilistic pairwise Markov models (PPMMs) to the prevalent Potts model by incorporating both into a novel computer aided diagnosis (CAD) system for detecting prostate cancer in whole-mount histological sections. Using the Potts model the CAD system is able to detection cancerous glands with a specificity of 0.82 and sensitivity of 0.71; its area under the receiver operator characteristic (AUC) curve is 0.83. If instead the PPMM model is employed the sensitivity (specificity is held fixed) and AUC increase to 0.77 and 0.87.

  20. Mouse Models of Prostate Cancer: Picking the Best Model for the Question

    PubMed Central

    Grabowska, Magdalena M.; DeGraff, David J.; Yu, Xiuping; Jin, Ren Jie; Chen, Zhenbang; Borowsky, Alexander D.; Matusik, Robert J.

    2014-01-01

    When the NIH Mouse Models of Human Cancer Consortium (MMCC) initiated the Prostate Steering Committee 15 years ago, there were no genetically engineered mouse (GEM) models of prostate cancer (PCa). Today, a PubMed search for “prostate cancer mouse model” yields 3,200 publications and this list continues to grow. The first generation of GEM utilized the newly discovered and characterized probasin (PB) promoter driving viral oncogenes such as SV40 large T antigen to yield the LADY and TRAMP models. As the PCa research field has matured, the second generation of models has incorporated the single and multiple molecular changes observed in human disease, such as loss of PTEN and over-expression of Myc. Application of these models has revealed that mice are particularly resistant to developing invasive PCa, and once they achieve invasive disease, the PCa rarely resembles human disease. Nevertheless, these models and their application have provided vital information on human PCa progression. The aim of this review is to provide a brief primer on mouse and human prostate histology and pathology, provide descriptions of mouse models, as well as attempt to answer the age old question: Which GEM model of PCa is the best for my research question? PMID:24452759

  1. Development of Pain End Point Models for Use in Prostate Cancer Clinical Trials and Drug Approval

    DTIC Science & Technology

    2014-10-01

    for Use in Prostate Cancer Clinical Trials and Drug Approval PRINCIPAL INVESTIGATOR: Dr. Ethan Basch CONTRACTING ORGANIZATION...Pain End Point Models for Use in Prostate Cancer Clinical Trials and Drug Approval 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...are feasible, methodologically rigorous, and meet regulatory requirements for drug approval and labeling. The primary aim of this award is to

  2. Developing a model for forecasting Gleason score ≥7 in potential prostate cancer patients to reduce unnecessary prostate biopsies.

    PubMed

    Li, Xiao; Pan, Yongsheng; Huang, Yuan; Wang, Jun; Zhang, Cheng; Wu, Jie; Cheng, Gong; Qin, Chao; Hua, Lixin; Wang, Zengjun

    2016-04-01

    The diagnosis of Gleason score (GS) ≥7 with distinction from GS < 7 remains a difficult problem instructing clinical decisions. Moreover, the present wide application of prostate biopsy to increase prostate cancer detection rate might cause unnecessary and excessive examination or treatment. Therefore, a risk assessment model for forecasting GS ≥ 7 in potential prostate cancer patients was established to reduce unnecessary prostate biopsies. Patients (n = 981; September 2009 to January 2013) who underwent trans-rectal ultrasound (TRUS)-guided core prostate biopsy were retrospectively evaluated in the first stage of the study. Age, prostate-specific antigen (PSA), free PSA (fPSA), the free/total PSA ratio (f/t), prostate volume (PV), PSA density (PSAD), digital rectal examination (DRE) findings (texture, nodules) and B-ultrasound detection results (normal or abnormal, presence of hypoechoic mass or microcalcification) were considered as potential predictive factors. After multiple logistic regression analysis, independent variables used to build a nomogram were selected using a backward elimination selection procedure. Then, a model to forecast GS ≥ 7 was designed for potential prostate cancer patients. In the second stage of the study, 410 cases (January 2013 to March 2015) were subsequently evaluated using our model for prostate biopsies, and the outcomes of biopsies were compared between the two stages. PSA, DRE texture, DRE nodules and B-ultrasound results were finally brought into our nomogram; a obviously greater area under the receiver operating characteristic (ROC) curve was obtained for the model than utilizing PSA, fPSA or PSAD alone (0.831 vs. 0.803, 0.770, 0.780 separately). We thereafter sought the best cutoff value in the ROC curve at 0.87, which provided sensitivity as high as 90%. Meanwhile, the specificity was 45.8%, which was much higher than the specificity of PSA, fPSA and PSAD at the same sensitivity level (37.7, 24.6 and 35

  3. Selenoproteins and Prostate Cancer

    DTIC Science & Technology

    2005-11-01

    1-0009 TITLE: Selenoproteins and Prostate Cancer PRINCIPAL INVESTIGATOR: Veda Navsariwala, Ph.D...Annual Summary 3. DATES COVERED (From - To) 15 Oct 2004 – 14 Oct 2005 4. TITLE AND SUBTITLE Selenoproteins and Prostate Cancer 5a. CONTRACT NUMBER...ABSTRACT For this postdoctoral fellowship the specific role of selenoproteins in prostate carcinogenesis is being investigated using a cell

  4. The Estradiol-Dihydrotestosterone model of prostate cancer

    PubMed Central

    Friedman, A Edward

    2005-01-01

    Background The exact relationship between hormonal activity and prostate cancer(PCa) has not yet been clearly defined. One of the key hormones associated with PCa is testosterone(T). However, both in vitro and in vivo studies have shown that under some conditions T is capable of either promoting PCa growth or death. This article proposes a theory which resolves this apparent paradox. Model The Estradiol-Dihydrotestosterone(E-D) model introduced in this paper proposes that 17β-estradiol(E2) is essential for initiating the growth of PCa cells through the formation of telomeres. It also proposes that T is responsible for increasing the expression of proteins which cause apoptosis, or programmed cell death, and that 5α-dihydrotestosterone(DHT) is essential for preventing this. In addition, it is known that some T is converted to both E2 and DHT, which means that depending on the conditions, T is capable of either promoting the growth of or the killing of PCa. PMID:15777479

  5. Biomarkers in localized prostate cancer.

    PubMed

    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

    2016-02-01

    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.

  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. 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.

  8. Targeting Prostate Cancer Metastasis

    DTIC Science & Technology

    2015-09-01

    drug t oxi c i t y and the e ffect i ve dose i n zebrafish and found the best perf ormi ng s t rat egi es usi ng zebrafish - metastasi s model s...CLASSIFICATION OF: a. REPORT b. ABSTRACT c . THIS PAGE Unclassified Unclassified Unclassified screen, zebrafish , mouse, 17. LIMITATION 18. NUMBER OF... zebrafish -metastasis models and mouse models of prostate cancer, we aim to investigate whether FDA approved drugs that target these pathways can be

  9. Genetics Home Reference: prostate cancer

    MedlinePlus

    ... Email Facebook Twitter Home Health Conditions prostate cancer prostate cancer Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Prostate cancer is a common disease that affects men, usually ...

  10. Hormone therapy for prostate cancer

    MedlinePlus

    ... gov/ency/patientinstructions/000908.htm Hormone therapy for prostate cancer To use the sharing features on this page, ... the growth of prostate cancer. Male Hormones and Prostate Cancer Androgens are male sex hormones. Testosterone is one ...

  11. Bifurcation analysis on a hybrid systems model of intermittent hormonal therapy for prostate cancer

    NASA Astrophysics Data System (ADS)

    Tanaka, Gouhei; Tsumoto, Kunichika; Tsuji, Shigeki; Aihara, Kazuyuki

    2008-10-01

    Hybrid systems are widely used to model dynamical phenomena that are characterized by interplay between continuous dynamics and discrete events. An example of biomedical application is modeling of disease progression of prostate cancer under intermittent hormonal therapy, where continuous tumor dynamics is switched by interruption and reinstitution of medication. In the present paper, we study a hybrid systems model representing intermittent androgen suppression (IAS) therapy for advanced prostate cancer. Intermittent medication with switching between on-treatment and off-treatment periods is intended to possibly prevent a prostatic tumor from developing into a hormone-refractory state and is anticipated as a possible strategy for delaying or hopefully averting a cancer relapse which most patients undergo as a result of long-term hormonal suppression. Clinical efficacy of IAS therapy for prostate cancer is still under investigation but at least worth considering in terms of reduction of side effects and economic costs during off-treatment periods. In the model of IAS therapy, it depends on some clinically controllable parameters whether a relapse of prostate cancer occurs or not. Therefore, we examine nonlinear dynamics and bifurcation structure of the model by exploiting a numerical method to clarify bifurcation sets in the hybrid system. Our results suggest that adjustment of the normal androgen level in combination with appropriate medication scheduling could enhance the possibility of relapse prevention. Moreover, a two-dimensional piecewise-linear system reduced from the original model highlights the origin of nonlinear phenomena specific to the hybrid system.

  12. Analysis of TMEFF2 allografts and transgenic mouse models reveals roles in prostate regeneration and cancer.

    PubMed

    Corbin, Joshua M; Overcash, Ryan F; Wren, Jonathan D; Coburn, Anita; Tipton, Greg J; Ezzell, Jennifer A; McNaughton, Kirk K; Fung, Kar-Ming; Kosanke, Stanley D; Ruiz-Echevarria, Maria J

    2016-01-01

    Previous results from our lab indicate a tumor suppressor role for the transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) in prostate cancer (PCa). Here, we further characterize this role and uncover new functions for TMEFF2 in cancer and adult prostate regeneration. The role of TMEFF2 was examined in PCa cells using Matrigel(TM) cultures and allograft models of PCa cells. In addition, we developed a transgenic mouse model that expresses TMEFF2 from a prostate specific promoter. Anatomical, histological, and metabolic characterizations of the transgenic mouse prostate were conducted. The effect of TMEFF2 in prostate regeneration was studied by analyzing branching morphogenesis in the TMEFF2-expressing mouse lobes and alterations in branching morphogenesis were correlated with the metabolomic profiles of the mouse lobes. The role of TMEFF2 in prostate tumorigenesis in whole animals was investigated by crossing the TMEFF2 transgenic mice with the TRAMP mouse model of PCa and analyzing the histopathological changes in the progeny. Ectopic expression of TMEFF2 impairs growth of PCa cells in Matrigel or allograft models. Surprisingly, while TMEFF2 expression in the TRAMP mouse did not have a significant effect on the glandular prostate epithelial lesions, the double TRAMP/TMEFF2 transgenic mice displayed an increased incidence of neuroendocrine type tumors. In addition, TMEFF2 promoted increased branching specifically in the dorsal lobe of the prostate suggesting a potential role in developmental processes. These results correlated with data indicating an alteration in the metabolic profile of the dorsal lobe of the transgenic TMEFF2 mice. Collectively, our results confirm the tumor suppressor role of TMEFF2 and suggest that ectopic expression of TMEFF2 in mouse prostate leads to additional lobe-specific effects in prostate regeneration and tumorigenesis. This points to a complex and multifunctional role for TMEFF2 during PCa

  13. ANALYSIS OF TMEFF2 ALLOGRAFTS AND TRANSGENIC MOUSE MODELS REVEALS ROLES IN PROSTATE REGENERATION AND CANCER

    PubMed Central

    Corbin, JM.; Overcash, RF.; Wren, JD.; Coburn, A.; Tipton, GJ.; Ezzell, JA.; McNaughton, KK.; Fung, KM; Kosanke, SD.; Ruiz-Echevarria, MJ

    2015-01-01

    BACKGROUND Previous results from our lab indicate a tumor suppressor role for the transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) in prostate cancer (PCa). Here, we further characterize this role and uncover new functions for TMEFF2 in cancer and adult prostate regeneration. METHODS The role of TMEFF2 was examined in PCa cells using Matrigel™ cultures and allograft models of PCa cells. In addition, we developed a transgenic mouse model that expresses TMEFF2 from a prostate specific promoter. Anatomical, histological and metabolic characterizations of the transgenic mouse prostate were conducted. The effect of TMEFF2 in prostate regeneration was studied by analyzing branching morphogenesis in the TMEFF2-expressing mouse lobes and alterations in branching morphogenesis were correlated with the metabolomic profiles of the mouse lobes. The role of TMEFF2 in prostate tumorigenesis in whole animals was investigated by crossing the TMEFF2 transgenic mice with the TRAMP mouse model of PCa and analyzing the histopathological changes in the progeny. RESULTS Ectopic expression of TMEFF2 impairs growth of PCa cells in Matrigel or allograft models. Surprisingly, while TMEFF2 expression in the TRAMP mouse did not have a significant effect on the glandular prostate epithelial lesions, the double TRAMP/TMEFF2 transgenic mice displayed an increased incidence of neuroendocrine type tumors. In addition, TMEFF2 promoted increased branching specifically in the dorsal lobe of the prostate suggesting a potential role in developmental processes. These results correlated with data indicating an alteration in the metabolic profile of the dorsal lobe of the transgenic TMEFF2 mice. CONCLUSIONS Collectively, our results confirm the tumor suppressor role of TMEFF2 and suggest that ectopic expression of TMEFF2 in mouse prostate leads to additional lobe-specific effects in prostate regeneration and tumorigenesis. This points to a complex and

  14. Novel syngeneic pseudo-orthotopic prostate cancer model: vascular, mitotic and apoptotic responses to castration.

    PubMed

    Frost, Gregory I; Lustgarten, Joseph; Dudouet, Brigitte; Nyberg, Linda; Hartley-Asp, Beryl; Borgström, Per

    2005-01-01

    We describe a novel syngeneic "pseudo-orthotopic" in vivo model of prostate cancer progression. Our model uses the dorsal skinfold chamber technique with fluorescence video microscopy and TRAMP-C2 tumor cells. The cells were transfected with a histone H2B-GFP fusion protein, permitting real-time measurement of tumor size, as well as mitotic and apoptotic indices. To generate a "pseudo-orthotopic" milieu, pieces of prostate tissue (10-15 mm2) from donor mice were implanted into the chambers of C57BL/6 mice. The prostate tissue grafted into the chambers retained its native vasculature, as determined by transplantation of prostate tissue from GFP transgenic mice. TRAMP-C2 prostate cancer tumor spheroids (25,000 cells) were implanted in the chamber. Without prostate tissue, TRAMP-C2 prostate tumors were poorly angiogenic, displayed low mitotic and apoptotic indices (0.7 x 10(-4)), and no significant tumor growth could be detected. TRAMP-C2 tumors growing on transplanted prostate tissue in the chamber on the other hand had mitotic indices in the order of 1.6 x 10(-4) and apoptotic indices in the order of 0.8 x 10(-4). Furthermore, tumors with stroma were highly angiogenic, and were fully vascularized within 7-10 days. During a 4-week observation period, the number of tumor cells increased by nearly 300%. We used the model to study the effects of surgical castration. The most profound response was a rapid vascular regression of the tumor vasculature. Castration also increased apoptotic indices within the tumor without significant changes in mitosis. This model may be utilized for the rapid analysis of new therapeutic candidates against prostate cancer.

  15. Selenoproteins and Prostate Cancer

    DTIC Science & Technology

    2006-11-01

    W81XWH-05-1-0009 TITLE: Selenoproteins and Prostate Cancer PRINCIPAL INVESTIGATOR: Veda Diwadkar-Navsariwala, Ph.D. CONTRACTING...From - To) 14 Oct 2004 – 14 Oct 2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Selenoproteins and Prostate Cancer 5b. GRANT NUMBER W81XWH-05...SUPPLEMENTARY NOTES 14. ABSTRACT For this postdoctoral fellowship the specific role of selenoproteins (SP) in prostate cancer (PCa) was

  16. Cancer Targeting Potential of (99m)Tc-Finasteride in Experimental Model of Prostate Carcinogenesis.

    PubMed

    Jan, Gowsia; Passi, Neelima D; Dhawan, Devinder Kumar; Chadha, Vijayta Dani

    2017-03-01

    This study aimed to radiolabel finasteride, a novel 5α-reductase inhibitor, to evaluate its cancer targeting potential in experimental model of prostate carcinogenesis. Finasteride was effectively radiolabeled with (99m)Tc and showed >90% labeling efficiency. The radiopharmaceutical was found to be stable up to 6 hours in rat serum at 37°C. The blood kinetics of the (99m)Tc-finasteride followed a biphasic release pattern, whereby fast-release phase was observed at 15 seconds and a slow-release phase was observed after 30 minutes of administration. The plasma protein binding of the radio complex observed was 83.89%. For biodistribution studies, the rats were divided into two groups. Group I served as normal controls, while group II was subjected to carcinogen N-methyl-N-nitrosourea (MNU) and hormone testosterone propionate (T) for induction of prostate carcinogenesis, which was confirmed histopathologically. The biodistribution studies on control and carcinogen-treated rats revealed a significant percent-specific uptake in prostate, which was found to be increased significantly as a function of time. The most significant finding of the study was an increase in the percent-specific uptake in prostate of carcinogen-treated animals when compared to the percent-specific uptake in prostate of normal rats after 2 and 4 hours postinjection. The study concludes that (99m)Tc-finasteride possesses selectively toward prostate cancer tissue and can be explored further for its role in detection of prostate cancer.

  17. Can a single model explain both breast cancer and prostate cancer?

    PubMed Central

    Friedman, A Edward

    2007-01-01

    Background The Estradiol-Dihydrotestosterone model of prostate cancer (PC) showed how the interaction of hormones with specific hormone receptors affected apoptosis. The same hormone can produce different effects, depending on which hormone receptor it interacts with. Model This model proposes that the first step in the development of most PC and breast cancer (BC) occurs when aromatase converts testosterone to estradiol (E2). A sufficiently high enough local level of E2 results in telomerase activity. The telomerase activity allows cell division and may lead to BC or PC, which will proliferate if the rate of cell division is greater than the rate of cell death. The effect of hormones on their hormone receptors will affect the rate of cell death and determine whether or not the cancer proliferates. Conclusion By minimizing bcl-2 and maximizing apoptotic proteins, new systemic treatments for BC and PC can be developed that may be more effective than existing treatments. PMID:17678531

  18. Humanized Androgen Receptor Mice: A Genetic Model for Differential Response to Prostate Cancer Therapy

    DTIC Science & Technology

    2010-05-01

    For each Q tract allele, we have currently obtained at least 30 experimental and 30 control mice . Some have reached their time points and tissues...overexpression of ETV1). Experimental mice have been generated and prostates are being microdissected as animals reach their time points. Initial...TITLE: Humanized Androgen Receptor Mice : A Genetic Model for Differential Response to Prostate Cancer Therapy PRINCIPAL INVESTIGATOR: Diane M

  19. Lipids and Prostate Cancer

    PubMed Central

    Suburu, Janel; Chen, Yong Q.

    2012-01-01

    The role of lipid metabolism has gained particular interest in prostate cancer research. A large body of literature has outlined the unique upregulation of de novo lipid synthesis in prostate cancer. Concordant with this lipogenic phenotype is a metabolic shift, in which cancer cells use alternative enzymes and pathways to facilitate the production of fatty acids. These newly synthesized lipids may support a number of cellular processes to promote cancer cell proliferation and survival. Hence, de novo lipogenesis is under intense investigation as a therapeutic target. Epidemiologic studies suggest dietary fat may also contribute to prostate cancer; however, whether dietary lipids and de novo synthesized lipids are differentially metabolized remains unclear. Here, we highlight the lipogenic nature of prostate cancer, especially the promotion of de novo lipid synthesis, and the significance of various dietary lipids in prostate cancer development and progression. PMID:22503963

  20. In vitro and in vivo model systems used in prostate cancer research

    PubMed Central

    Cunningham, David; You, Zongbing

    2015-01-01

    New incidence of prostate cancer is a major public health issue in the Western world, and has been rising in other areas of the globe in recent years. In an effort to understanding the molecular pathogenesis of this disease, numerous cell models have been developed, arising mostly from patient biopsies. The introduction of the genetically engineered mouse in biomedical research has allowed the development of murine models that allow for the investigation of tumorigenic and metastatic processes. Current challenges to the field include lack of an animal model that faithfully recapitulates bone metastasis of prostate cancer. PMID:26146646

  1. Prostate Cancer

    MedlinePlus

    ... cancers that don't respond to hormone therapy. Biological therapy Biological therapy (immunotherapy) uses your body's immune system to fight cancer cells. One type of biological therapy called sipuleucel-T (Provenge) has been developed ...

  2. An improved prognostic model for stage T1a and T1b prostate cancer by assessments of cancer extent

    PubMed Central

    Rajab, Ramzi; Fisher, Gabrielle; Kattan, Michael W; Foster, Christopher S; Møller, Henrik; Oliver, Tim; Reuter, Victor; Scardino, Peter T; Cuzick, Jack; Berney, Daniel M

    2013-01-01

    Treatment decisions on prostate cancer diagnosed by trans-urethral resection (TURP) of the prostate are difficult. The current TNM staging system for pT1 prostate cancer has not been re-evaluated for 25 years. Our objective was to optimise the predictive power of tumor extent measurements in TURP of the prostate specimens. A total of 914 patients diagnosed by TURP of the prostate between 1990 and 1996, managed conservatively were identified. The clinical end point was death from prostate cancer. Diagnostic serum prostate-specific antigen (PSA) and contemporary Gleason grading was available. Cancer extent was measured by the percentage of chips infiltrated by cancer. Death rates were compared by univariate and multivariate proportional hazards models, including baseline PSA and Gleason score. The percentage of positive chips was highly predictive of prostate cancer death when assessed as a continuous variable or as a grouped variable on the basis of and including the quintiles, quartiles, tertiles and median groups. In the univariate model, the most informative variable was a four group-split (≤ 10%, >10–25%, > 25–75% and > 75%); (HR = 2.08, 95% CI = 1.8–2.4, P < 0.0001). The same was true in a multivariate model (ΔX2 (1 d.f.) = 15.0, P = 0.0001). The current cutoff used by TNM (< = 5%) was sub-optimal (ΔX2 (1 d.f.) = 4.8, P = 0.023). The current TNM staging results in substantial loss of information. Staging by a four-group subdivision would substantially improve prognostication in patients with early stage disease and also may help to refine management decisions in patients who would do well with conservative treatments. PMID:20834240

  3. Models for predicting objective function weights in prostate cancer IMRT

    SciTech Connect

    Boutilier, Justin J. Lee, Taewoo; Craig, Tim; Sharpe, Michael B.; Chan, Timothy C. Y.

    2015-04-15

    Purpose: To develop and evaluate the clinical applicability of advanced machine learning models that simultaneously predict multiple optimization objective function weights from patient geometry for intensity-modulated radiation therapy of prostate cancer. Methods: A previously developed inverse optimization method was applied retrospectively to determine optimal objective function weights for 315 treated patients. The authors used an overlap volume ratio (OV) of bladder and rectum for different PTV expansions and overlap volume histogram slopes (OVSR and OVSB for the rectum and bladder, respectively) as explanatory variables that quantify patient geometry. Using the optimal weights as ground truth, the authors trained and applied three prediction models: logistic regression (LR), multinomial logistic regression (MLR), and weighted K-nearest neighbor (KNN). The population average of the optimal objective function weights was also calculated. Results: The OV at 0.4 cm and OVSR at 0.1 cm features were found to be the most predictive of the weights. The authors observed comparable performance (i.e., no statistically significant difference) between LR, MLR, and KNN methodologies, with LR appearing to perform the best. All three machine learning models outperformed the population average by a statistically significant amount over a range of clinical metrics including bladder/rectum V53Gy, bladder/rectum V70Gy, and dose to the bladder, rectum, CTV, and PTV. When comparing the weights directly, the LR model predicted bladder and rectum weights that had, on average, a 73% and 74% relative improvement over the population average weights, respectively. The treatment plans resulting from the LR weights had, on average, a rectum V70Gy that was 35% closer to the clinical plan and a bladder V70Gy that was 29% closer, compared to the population average weights. Similar results were observed for all other clinical metrics. Conclusions: The authors demonstrated that the KNN and MLR

  4. 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.

  5. [Prostate cancer screening].

    PubMed

    Villers, Arnauld; Rébillard, Xavier; Soulié, Michel; Davin, Jean-Louis; Coloby, Patrick; Moreau, Jean-Luc; Mejean, Arnaud; Irani, Jacques; Coulange, Christian; Mangin, Philippe

    2003-04-01

    Prostate cancer has become the most frequent cancer and the second cause of cancer mortality in men. This public health problem is becoming increasingly important due to the increasing life expectancy. At the present time, prostate cancer will be discovered in one in every eight men during their lifetime. Prostate cancer represents 25% of all new cases of male cancers. Prostate cancer screening is designed to detect early stage, asymptomatic prostate cancer, as the patient's chances of cure are higher when the cancer is diagnosed at an early stage. The conclusions of the ANAES evaluation in 1998 did not recommend mass screening for prostate cancer. Several international prospective randomized studies based on serum PSA assay, sometimes associated with digital rectal examination, are currently underway. France is participating in the European ERSPC study (European Randomized Study of Screening for Cancer Prostate) and is organizing a national study on high-risk populations. While waiting for the final results of these studies, a recommendation needs to be proposed to inform general practitioners and specialists about optimal use of the currently available tests. Based on the conclusions of its oncology committee (composed of urologists, medical oncologists, radiotherapists, pathologists and radiologists), the Association Française d'Urologie proposes a recommendation concerning prostate cancer screening and defines its modalities, especially concerning the target population, screening tests and the information given to men before screening. The Association Française d'Urologie recommends prostate cancer screening by PSA assay (prostate specific antigen) and digital rectal examination annually between the ages of 50 and 75 years, and from the age of 45 years in men with a family or ethnic risk. If total PSA is above the normal value of the test or if digital rectal examination is abnormal, referral to a urologist is recommended. Information concerning the limits

  6. Breaking through a roadblock in prostate cancer research: an update on human model systems.

    PubMed

    Toivanen, R; Taylor, R A; Pook, D W; Ellem, S J; Risbridger, G P

    2012-09-01

    Prostate cancer is a prevalent disease that affects the aging male population. Whilst there have been significant advances of our biological understanding of the disease, clinical translation of promising agents continues to lag behind. In part, this is due to a paucity of relevant experimental and pre-clinical models required to further develop effective prevention and therapeutic strategies. Genetically modified cell lines fail to entirely represent the genetic and molecular diversity of primary human specimens, particularly from localised disease. Furthermore, primary prostate cancer tissues are extremely difficult to grow in the laboratory and virtually all human models, whether they grow as xenografts in immune-deficient animals or as cell cultures, are genetically modified by the investigator or derived from patients with advanced metastatic disease. In this review, we discuss the latest advances and improvements to current methods of xenografting human primary prostate cancer, and their potential application to translational research.

  7. Development of animal models underlining mechanistic connections between prostate inflammation and cancer.

    PubMed

    Mimeault, Murielle; Batra, Surinder K

    2013-02-10

    The characterization of animal models has indicated that the genetic, dietary and environmental factors and hormonal imbalance may influence the risk to develop prostate inflammatory lesions and prostate cancer (PC) confirming human epidemiologic data. It is now established that the prostate inflammatory response typically results in major changes in the local microenvironment of epithelial cells of the prostate gland, including an intense stromal remodeling, activation of fibroblasts, infiltration of immune cells such as mast cells, macrophages and B and T lymphocytes and collagen deposition. The immune cells recruited at prostate inflammatory lesions and myofibroblasts may contribute to the release of numerous pro-inflammatory cytokines and chemokines that in turn can promote the oxidative stress, genomic instability and proliferation of epithelial cells. The accumulation of additional genetic and/or epigenetic alterations in prostatic stem/progenitor cells may subsequently culminate to their malignant transformation and PC initiation and progression and more particularly with advancing age. The potential mechanistic relationships between the molecular events associated with the persistent inflammatory response and prostate carcinogenesis have important implications for optimizing the current therapies against different prostatic disorders and PCs.

  8. Prostate cancer risk and DNA damage: translational significance of selenium supplementation in a canine model.

    PubMed

    Waters, David J; Shen, Shuren; Glickman, Lawrence T; Cooley, Dawn M; Bostwick, David G; Qian, Junqi; Combs, Gerald F; Morris, J Steven

    2005-07-01

    Daily supplementation with the essential trace mineral selenium significantly reduced prostate cancer risk in men in the Nutritional Prevention of Cancer Trial. However, the optimal intake of selenium for prostate cancer prevention is unknown. We hypothesized that selenium significantly regulates the extent of genotoxic damage within the aging prostate and that the relationship between dietary selenium intake and DNA damage is non-linear, i.e. more selenium is not necessarily better. To test this hypothesis, we conducted a randomized feeding trial in which 49 elderly beagle dogs (physiologically equivalent to 62-69-year-old men) received nutritionally adequate or supranutritional levels of selenium for 7 months, in order to mimic the range of dietary selenium intake of men in the United States. Our results demonstrate an intriguing U-shaped dose-response relationship between selenium status (toenail selenium concentration) and the extent of DNA damage (alkaline Comet assay) within the prostate. Further, we demonstrate that the concentration of selenium that minimizes DNA damage in the aging dog prostate remarkably parallels the selenium concentration in men that minimizes prostate cancer risk. By studying elderly dogs, the only non-human animal model of spontaneous prostate cancer, we have established a new approach to bridge the gap between laboratory and human studies that can be used to select the appropriate dose of anticancer agents for large-scale human cancer prevention trials. From the U-shaped dose-response, it follows that not all men will necessarily benefit from increasing their selenium intake and that measurement of baseline nutrient status should be required for all individuals in prevention trials to avoid oversupplementation.

  9. Prostate Cancer Biorepository Network

    DTIC Science & Technology

    2015-10-01

    annotated with the biospecimens. Specialized processing consists of tissue microarray design and construction. Biospecimens (mainly tissue ...provide much sought after biospecimens for prostate cancer research. 15. SUBJECT TERMS Prostate Cancer, Biorepository, tissue microarrays, tissue ...and harmonizing a set of common data elements (CDEs): Completed in 1st quarter (October 2014) Task 3. Submit SOPs currently in use to Coordinating

  10. 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 ...

  11. A clinical data validated mathematical model of prostate cancer growth under intermittent androgen suppression therapy

    NASA Astrophysics Data System (ADS)

    Portz, Travis; Kuang, Yang; Nagy, John D.

    2012-03-01

    Prostate cancer is commonly treated by a form of hormone therapy called androgen suppression. This form of treatment, while successful at reducing the cancer cell population, adversely affects quality of life and typically leads to a recurrence of the cancer in an androgen-independent form. Intermittent androgen suppression aims to alleviate some of these adverse affects by cycling the patient on and off treatment. Clinical studies have suggested that intermittent therapy is capable of maintaining androgen dependence over multiple treatment cycles while increasing quality of life during off-treatment periods. This paper presents a mathematical model of prostate cancer to study the dynamics of androgen suppression therapy and the production of prostate-specific antigen (PSA), a clinical marker for prostate cancer. Preliminary models were based on the assumption of an androgen-independent (AI) cell population with constant net growth rate. These models gave poor accuracy when fitting clinical data during simulation. The final model presented hypothesizes an AI population with increased sensitivity to low levels of androgen. It also hypothesizes that PSA production is heavily dependent on androgen. The high level of accuracy in fitting clinical data with this model appears to confirm these hypotheses, which are also consistent with biological evidence.

  12. Lung Cancer Risk Prediction: Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial Models and Validation

    PubMed Central

    Pinsky, Paul F.; Caporaso, Neil E.; Kvale, Paul A.; Hocking, William G.; Church, Timothy R.; Riley, Thomas L.; Commins, John; Oken, Martin M.; Berg, Christine D.; Prorok, Philip C.

    2011-01-01

    Introduction Identification of individuals at high risk for lung cancer should be of value to individuals, patients, clinicians, and researchers. Existing prediction models have only modest capabilities to classify persons at risk accurately. Methods Prospective data from 70 962 control subjects in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) were used in models for the general population (model 1) and for a subcohort of ever-smokers (N = 38 254) (model 2). Both models included age, socioeconomic status (education), body mass index, family history of lung cancer, chronic obstructive pulmonary disease, recent chest x-ray, smoking status (never, former, or current), pack-years smoked, and smoking duration. Model 2 also included smoking quit-time (time in years since ever-smokers permanently quit smoking). External validation was performed with 44 223 PLCO intervention arm participants who completed a supplemental questionnaire and were subsequently followed. Known available risk factors were included in logistic regression models. Bootstrap optimism-corrected estimates of predictive performance were calculated (internal validation). Nonlinear relationships for age, pack-years smoked, smoking duration, and quit-time were modeled using restricted cubic splines. All reported P values are two-sided. Results During follow-up (median 9.2 years) of the control arm subjects, 1040 lung cancers occurred. During follow-up of the external validation sample (median 3.0 years), 213 lung cancers occurred. For models 1 and 2, bootstrap optimism-corrected receiver operator characteristic area under the curves were 0.857 and 0.805, and calibration slopes (model-predicted probabilities vs observed probabilities) were 0.987 and 0.979, respectively. In the external validation sample, models 1 and 2 had area under the curves of 0.841 and 0.784, respectively. These models had high discrimination in women, men, whites, and nonwhites. Conclusion The PLCO

  13. Combined Treatment Effects of Radiation and Immunotherapy: Studies in an Autochthonous Prostate Cancer Model

    SciTech Connect

    Wada, Satoshi; Harris, Timothy J.; Tryggestad, Erik; Yoshimura, Kiyoshi; Zeng, Jing; Yen, Hung-Rong; Getnet, Derese; Grosso, Joseph F.; Bruno, Tullia C.; De Marzo, Angelo M.; and others

    2013-11-15

    Purpose: To optimize the combination of ionizing radiation and cellular immunotherapy using a preclinical autochthonous model of prostate cancer. Methods and Materials: Transgenic mice expressing a model antigen under a prostate-specific promoter were treated using a platform that integrates cone-beam CT imaging with 3-dimensional conformal therapy. Using this technology we investigated the immunologic and therapeutic effects of combining ionizing radiation with granulocyte/macrophage colony-stimulating factor-secreting cellular immunotherapy for prostate cancer in mice bearing autochthonous prostate tumors. Results: The combination of ionizing radiation and immunotherapy resulted in a significant decrease in pathologic tumor grade and gross tumor bulk that was not evident with either single-modality therapy. Furthermore, combinatorial therapy resulted in improved overall survival in a preventive metastasis model and in the setting of established micrometastases. Mechanistically, combined therapy resulted in an increase of the ratio of effector-to-regulatory T cells for both CD4 and CD8 tumor-infiltrating lymphocytes. Conclusions: Our preclinical model establishes a potential role for the use of combined radiation-immunotherapy in locally advanced prostate cancer, which warrants further exploration in a clinical setting.

  14. Infections and inflammation in prostate cancer

    PubMed Central

    Sfanos, Karen S; Isaacs, William B; Marzo, Angelo M De

    2013-01-01

    The frequent observation of both acute and chronic inflammation of unknown stimulus in the adult prostate has motivated a large body of research aimed at identifying potential infectious agents that may elicit prostatic inflammation. The overarching hypothesis is that infection-induced inflammation may be associated with prostate cancer development or progression, as inflammation is known to serve as an “enabling characteristic” of cancer. With recent advances in molecular techniques for microorganism identification, a panoply of microorganisms has been scrutinized in prostate tissues and in relation to prostate carcinogenesis. The aim of this review is to summarize the current literature on the evidence for infectious agents as a contributing factor to prostatic inflammation and prostate cancer, and to highlight recent literature suggesting an infectious etiology to the biogenesis of prostatic corpora amylacea and on the development of mouse models of prostatic infections. PMID:25110720

  15. Infections and inflammation in prostate cancer.

    PubMed

    Sfanos, Karen S; Isaacs, William B; De Marzo, Angelo M

    2013-12-25

    The frequent observation of both acute and chronic inflammation of unknown stimulus in the adult prostate has motivated a large body of research aimed at identifying potential infectious agents that may elicit prostatic inflammation. The overarching hypothesis is that infection-induced inflammation may be associated with prostate cancer development or progression, as inflammation is known to serve as an "enabling characteristic" of cancer. With recent advances in molecular techniques for microorganism identification, a panoply of microorganisms has been scrutinized in prostate tissues and in relation to prostate carcinogenesis. The aim of this review is to summarize the current literature on the evidence for infectious agents as a contributing factor to prostatic inflammation and prostate cancer, and to highlight recent literature suggesting an infectious etiology to the biogenesis of prostatic corpora amylacea and on the development of mouse models of prostatic infections.

  16. [Benign prostatic hypertrophy and prostate cancer].

    PubMed

    Mourey, Loïc; Doumerc, Nicolas; Gaudin, Clément; Gérard, Stéphane; Balardy, Laurent

    2014-01-01

    Prostatic diseases are extremely common, especially in older men. Amongst them, benign prostatic hypertrophy may affect significantly the quality of life of patients by the symptoms it causes. It requires appropriate care. Prostate cancer is the second most common cancer in men after lung cancer and the fifth leading cause of cancer deaths in the world. It affects preferentially older men. An oncogeriatric approach is required for personalised care.

  17. Chemoprevention of prostate cancer.

    PubMed

    Vemana, Goutham; Hamilton, Robert J; Andriole, Gerald L; Freedland, Stephen J

    2014-01-01

    Large prospective randomized trials, such as the Prostate Cancer Prevention Trial (PCPT), Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, and Selenium and Vitamin E Cancer Prevention Trial (SELECT), have provided practitioners with considerable data regarding methods of treatment and prevention of prostate cancer. The best-studied medications for prevention are 5 alpha-reductase inhibitors. Their efficacy and side effects are well characterized. Other medications, dietary nutrients, and supplements have not been as well studied and generally do not demonstrate efficacy for disease prevention with an acceptable level of evidence.

  18. Translocator Protein PET Imaging in a Preclinical Prostate Cancer Model.

    PubMed

    Tantawy, Mohammed N; Charles Manning, H; Peterson, Todd E; Colvin, Daniel C; Gore, John C; Lu, Wenfu; Chen, Zhenbang; Chad Quarles, C

    2017-08-18

    The identification and targeting of biomarkers specific to prostate cancer (PCa) could improve its detection. Given the high expression of translocator protein (TSPO) in PCa, we investigated the use of [(18)F]VUIIS1008 (a novel TSPO-targeting radioligand) coupled with positron emission tomography (PET) to identify PCa in mice and to characterize their TSPO uptake. Pten(pc-/-), Trp53(pc-/-) prostate cancer-bearing mice (n = 9, 4-6 months old) were imaged in a 7T MRI scanner for lesion localization. Within 24 h, the mice were imaged using a microPET scanner for 60 min in dynamic mode following a retro-orbital injection of ~ 18 MBq [(18)F]VUIIS1008. Following imaging, tumors were harvested and stained with a TSPO antibody. Regions of interest (ROIs) were drawn around the tumor and muscle (hind limb) in the PET images. Time-activity curves (TACs) were recorded over the duration of the scan for each ROI. The mean activity concentrations between 40 and 60 min post radiotracer administration between tumor and muscle were compared. Tumor presence was confirmed by visual inspection of the MR images. The uptake of [(18)F]VUIIS1008 in the tumors was significantly higher (p < 0.05) than that in the muscle, where the percent injected dose per unit volume for tumor was 7.1 ± 1.6 % ID/ml and that of muscle was < 1 % ID/ml. In addition, positive TSPO expression was observed in tumor tissue analysis. The foregoing preliminary data suggest that TSPO may be a useful biomarker of PCa. Therefore, using TSPO-targeting PET ligands, such as [(18)F]VUIIS1008, may improve PCa detectability and characterization.

  19. Biomarkers for prostate cancer.

    PubMed

    Leman, Eddy S; Getzenberg, Robert H

    2009-09-01

    The detection of prostate cancer using a blood test has by many standards changed the face of the disease. Despite this tremendous success, there are limitations attributed to the use of prostate specific antigen (PSA) as a means to screen and detect prostate cancer. PSA, as its name implies, is not specific for prostate cancer and as such is often found elevated in other prostatic diseases/symptoms associated with the aging male. Clearly, more specific marker(s) that could identify which individuals actually have prostate cancer and differentiate them from those without the disease would be of tremendous value. The search for more accurate and clinically useful biomarkers of prostate cancer has been extensive. This has focused on individual markers, as well as groups of markers. Included among these are PSA isoforms, pathological indicators and stains, nucleic acids and others. This article highlights the discovery of PSA as a first blood-based biomarker for prostate cancer detection, as well as other molecular biomarkers and their potential application in detection of the disease. (c) 2009 Wiley-Liss, Inc.

  20. Cryosurgery for prostate cancer.

    PubMed

    Fahmy, W E; Bissada, N K

    2003-01-01

    Choice of management for patients with prostate cancer is influenced by patient and disease characteristics and life expectancy. Management options include expectance (watchful waiting), radical prostatectomy, external beam radiotherapy, brachytherapy, and cryosurgical ablation of the prostate (CSAP). The role of cryotherapy in the management of prostate cancer is still evolving. Continued research has allowed the introduction of efficient and safe cryosurgical equipment exemplified by the current third-generation cryosurgical machines. CSAP can be performed in an ambulatory surgery setting or as inpatient surgery with overnight stay. The procedure is performed under continuous ultrasonic monitoring. Mature data from the use of second-generation cryosurgical equipment indicate that CSAP is an effective therapeutic modality for managing patients with prostate cancer. Current data with the third-generation cryosurgical equipment are not mature. However, the favorable side effect profile and the good early responses seem to indicate that this modality will have a prominent role in the management of patients with prostate cancer.

  1. Establishment of a syngeneic orthotopic model of prostate cancer in immunocompetent rats

    PubMed Central

    Suzuki, Shugo; Naiki-Ito, Aya; Kuno, Toshiya; Punfa, Wanisa; Long, Ne; Kato, Hiroyuki; Inaguma, Shingo; Komiya, Masami; Shirai, Tomoyuki; Takahashi, Satoru

    2014-01-01

    We previously established 3 cell lines (PLS10, PLS20 and PLS30) from a chemically-induced prostate carcinoma in F344 rats, and demonstrated high potential for metastasis in nude mice. In the present study, we investigated the feasibility of establishing an orthotopic model using the 3 rat prostate cancer cell lines in immunocompetent rats with the aim of resolving species-mismatch problems and defects of immune systems. The PLS10, PLS20 and PLS30 cell lines were injected into the ventral prostates of 6-week-old rats, which were then sacrificed at experimental weeks 4 and 8. Tumor mass formation was found in rats with PLS10, but not in those with PLS20 or PLS30. Additionally, metastatic carcinomas could be detected in lymph nodes and lungs of PLS10-inoculated rats. Genetic analysis demonstrated K-ras gene mutations in PLS10 and PLS20, but not in PLS30 cells. There were no mutations in p53 and KLF6. In conclusion, we established a syngeneic orthotopic model for prostate cancer in immunocompetent rats simulating human castration-resistant prostate cancer (CRPC), which should prove useful for development and validation of therapeutic agents, especially with immunotherapy. PMID:26023257

  2. A multi-attribute model of prostate cancer patient's preferences for health states.

    PubMed

    Chapman, G B; Elstein, A S; Kuzel, T M; Nadler, R B; Sharifi, R; Bennett, C L

    1999-05-01

    Multi-attribute utility theory (MAUT) provides a way to model decisions involving trade-offs among different aspects or goals of a problem. We used MAUT to model prostate cancer patients' preferences for their own health state and we compared this model to patients' global judgments of health state utility. 57 patients with prostate cancer (mean age = 70) at two Chicago Veterans Administration health clinics were asked to evaluate health states described in terms of five health attributes affected by prostate cancer: pain, mood, sexual function, bladder and bowel function, and fatigue and energy. Each attribute had three levels that were used to form three clinically realistic health state descriptions (A = high, B = moderate, C = low). A fourth personalized health description (P) matched the patient's current health. We first measured patients' preferences using time trade-off (TTO) judgments for the three health states (A, B, and C) and for their own current health state (P). The TTO for the patient's own health state (P) was standardized by comparing it to TTO judgments for states A and C. We next constructed a multi-attribute model using the relative importance of the five attributes. The MAU scores were moderately correlated with the TTO preference judgments for the personalized state (Pearson r = 0.38, N = 57, p < 0.01). Thus, patients' preference judgments are moderately consistent and systematic. MAUT appears to be a potentially feasible method for evaluating preferences of prostate cancer patients and may prove helpful in assisting with patient decision making.

  3. Drugs Approved for Prostate Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Prostate Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Prostate Cancer Abiraterone Acetate Bicalutamide Cabazitaxel Casodex (Bicalutamide) Degarelix Docetaxel ...

  4. Chemoprevention of prostate cancer.

    PubMed

    Brand, Timothy C; Canby-Hagino, Edith D; Pratap Kumar, A; Ghosh, Rita; Leach, Robin J; Thompson, Ian M

    2006-08-01

    Prostate cancer is a common malignancy with multiple potential opportunities for cancer prevention. As the genetic basis of this malignancy is further understood, prevention strategies will be developed for individual patients based on specific risk factors and pathways of carcinogenesis. The PCPT has conclusively proven that prostate cancer prevention is possible. The results of the SELECT should be available within several years. An enormous challenge for the medical community will be the development of an efficient strategy to evaluate the substantial number of dietary, behavioral, and pharmacologic prevention opportunities. Ultimately, the goal of prostate can-cer prevention is to (1) identify men who are destined to develop clinically significant prostate cancer, and (2) provide individualized agents to prevent disease development.

  5. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1

    DTIC Science & Technology

    2008-02-01

    either omega (n)-3 or n-6 polyunsaturated fatty acids ( PUFAs ) directly impact PCa tumor growth. Furthermore, the FLiMP mice, which overexpress human 15...effects of excessive n-6 LA diet consumption in the progression of PCa. 15. SUBJECT TERMS Linoleic acid ; LO or LOX, lipoxygenase; PUFA , Polyunsaturated... fatty acid ; PCa, Prostate Cancer, MMHCC, Mouse Models of Human Cancer Consortium; IHC, immunohistochemistry; H & E, Hematoxylin and Eosin; FLiMP

  6. Preventing and Treating Prostate Cancer Spread to Bone

    MedlinePlus

    ... Prostate Cancer Treating Prostate Cancer Preventing and Treating Prostate Cancer Spread to Bones If prostate cancer spreads to ... Away or Comes Back After Treatment More In Prostate Cancer About Prostate Cancer Causes, Risk Factors, and Prevention ...

  7. Generation of a syngeneic orthotopic transplant model of prostate cancer metastasis

    PubMed Central

    Ellis, Leigh; Lehet, Kristin; Ku, ShengYu; Azabdaftari, Gissou; Pili, Roberto

    2014-01-01

    Progression to metastatic disease is the primary cause of mortality in men with prostate cancer (PCa). Mouse models which progress with spontaneous metastasis are limited. Such models would allow for extensive studies of molecular mechanisms of metastasis, and more definite pre- clinical therapy trials. Orthotopic murine models have been described; however a limiting biology of these models is their lack of an intact immune system. Within, we describe the development of an androgen sensitive and castrate resistant tractable orthotopic murine syngeneic (immune competent) model of prostate cancer. Both models develop primary tumors which spontaneously progress to metastatic disease in lymph tissue. These models will allow for more complete mechanistic and therapeutic studies in a short time period. PMID:25485289

  8. Advanced Prostate Cancer

    MedlinePlus

    ... if it has spread to: • Bones • Lungs • Liver • Brain • Lymph nodes outside the pelvis • Other organs You may be diagnosed with metastatic prostate cancer when you are first diagnosed, after having completed ...

  9. Obesity and prostate enlargement in men with localized prostate cancer.

    PubMed

    Kopp, Ryan P; Han, Misop; Partin, Alan W; Humphreys, Elizabeth; Freedland, Stephen J; Parsons, J Kellogg

    2011-12-01

    What's known on the subject? and What does the study add? Obesity is associated with prostate enlargement in men without prostate cancer. This study demonstrates an association between obesity and prostate enlargement in men with prostate cancer, and leads to possible implications for prostate cancer screening and diagnosis. • To determine if obesity is associated with prostate size in men with prostate cancer. • We examined preoperative body mass index (BMI) and whole prostate weight in a cohort of 16,325 patients undergoing radical prostatectomy for localized prostate cancer from 1975 to 2008 at a single institution. • We used multivariable regression modelling adjusting for age, year of surgery, preoperative serum prostate-specific antigen (PSA), pathological stage and Gleason grade. • Of the entire cohort, 13,343 (82%) patients had a prostate weight of at least 40 g. These men were older (P < 0.001), had a higher preoperative BMI (P < 0.002), higher preoperative PSA (P < 0.001), and were more likely to have pT2 disease (P < 0.001). • In multivariable regression, preoperative BMI was associated with increased prostate weight: for each 1 kg/m(2) increase in BMI, prostate weight increased by 0.45 g (95% CI 0.35-0.55, P-trend < 0.001). • Compared with men with BMI < 25 kg/m(2) , men with a BMI ≥35 kg/m(2) had a 40% (odds ratio 1.40, 95% CI 1.01-1.95) increased risk of prostate weight of at least 40 g and a 70% (odds ratio 1.70, 95% CI 1.32-2.20) increased risk of prostate weight of at least 50 g. • In men with localized prostate cancer, obesity is associated with an increased risk of prostate enlargement. • These data validate other observations linking obesity with prostate enlargement and may have important ramifications for prostate cancer diagnosis in obese men. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

  10. Regulation of the Prostate Cancer Tumor Microenvironment

    DTIC Science & Technology

    2013-04-01

    epithelium , stroma, as well as immune system, and the fixed nature of the prostate model with expression of the large T antigen, which may have limited...cancer glandular architecture formed (Figure 8). Figure 8. Subcutanous TRAMP Model to Recapitulate Prostate Cancer. TRAMP C2 cells with and...model to be able to alter the aggressiveness of the tumor and specifically modulate the TLR signaling pathway in prostate epithelium , stroma, and immune

  11. Advancing the Capabilities of an Authentic Ex Vivo Model of Primary Human Prostate Cancer

    DTIC Science & Technology

    2014-10-01

    which slices of human PCa are embedded under the renal capsules of immune-deficient mice (21, 22). The TSG model will benefit from extending the...performed sub- renal implantation of benign TSCs that have been cultured for 3 days, combining the in vitro TSC and in vivo TSG models . Future work...characterization of in vivo tumorgraft models for primary prostate cancer in which thin, precision-cut slices of tissue are implanted under the renal

  12. Lycium barbarum polysaccharides induce apoptosis in human prostate cancer cells and inhibits prostate cancer growth in a xenograft mouse model of human prostate cancer.

    PubMed

    Luo, Qiong; Li, Zhuoneng; Yan, Jun; Zhu, Fan; Xu, Ruo-Jun; Cai, Yi-Zhong

    2009-08-01

    Lycium barbarum polysaccharides (LBPs) are important functional constituents in red-colored fruits of L. barbarum (Guo Qi Zi, a well-known traditional Chinese medicinal plant commonly known as Goji berry or wolfberry). The influence of LBP on human prostate cancer cells was systematically investigated in vitro and in vivo. The in vitro effects of LBP on two cell lines (PC-3 and DU-145) were examined by using trypan blue exclusion staining, single-cell gel electrophoresis, flow cytometry, terminal dUTP nick-end labeling assay, and immunohistochemical assay (assessment of Bcl-2 and Bax expression). The in vivo effect of LBP on PC-3 cells was assessed in the nude mouse xenograft tumor model. The in vitro results showed that LBP can dose- and time-dependently inhibit the growth of both PC-3 and DU-145 cells. LBP caused the breakage of DNA strands of PC-3 and DU-145 cells; the tail frequency and tail length were significantly higher than that of control cells. LBP also markedly induced PC-3 and DU-145 cell apoptosis, with the highest apoptosis rates at 41.5% and 35.5%, respectively. The ratio of Bcl-2/Bax protein expression following LBP treatments decreased significantly with a dose-effect relationship, which suggested that LBP can regulate the expression of Bcl-2 and Bax to induce apoptosis of PC-3 and DU-145 cells. The in vivo experimental results indicate that LBP might significantly inhibit PC-3 tumor growth in nude mice. Both the tumor volume and weight of the LBP treatment group were significantly lower than those of the control group.

  13. Optimizing heat shock protein expression induced by prostate cancer laser therapy through predictive computational models

    NASA Astrophysics Data System (ADS)

    Rylander, Marissa N.; Feng, Yusheng; Zhang, Yongjie; Bass, Jon; Stafford, Roger J.; Hazle, John D.; Diller, Kenneth R.

    2006-07-01

    Thermal therapy efficacy can be diminished due to heat shock protein (HSP) induction in regions of a tumor where temperatures are insufficient to coagulate proteins. HSP expression enhances tumor cell viability and imparts resistance to chemotherapy and radiation treatments, which are generally employed in conjunction with hyperthermia. Therefore, an understanding of the thermally induced HSP expression within the targeted tumor must be incorporated into the treatment plan to optimize the thermal dose delivery and permit prediction of the overall tissue response. A treatment planning computational model capable of predicting the temperature, HSP27 and HSP70 expression, and damage fraction distributions associated with laser heating in healthy prostate tissue and tumors is presented. Measured thermally induced HSP27 and HSP70 expression kinetics and injury data for normal and cancerous prostate cells and prostate tumors are employed to create the first HSP expression predictive model and formulate an Arrhenius damage model. The correlation coefficients between measured and model predicted temperature, HSP27, and HSP70 were 0.98, 0.99, and 0.99, respectively, confirming the accuracy of the model. Utilization of the treatment planning model in the design of prostate cancer thermal therapies can enable optimization of the treatment outcome by controlling HSP expression and injury.

  14. Optimizing heat shock protein expression induced by prostate cancer laser therapy through predictive computational models.

    PubMed

    Rylander, Marissa Nichole; Feng, Yusheng; Zhang, Yongjie; Bass, Jon; Jason Stafford, R; Volgin, Andrei; Hazle, John D; Diller, Kenneth R

    2006-01-01

    Thermal therapy efficacy can be diminished due to heat shock protein (HSP) induction in regions of a tumor where temperatures are insufficient to coagulate proteins. HSP expression enhances tumor cell viability and imparts resistance to chemotherapy and radiation treatments, which are generally employed in conjunction with hyperthermia. Therefore, an understanding of the thermally induced HSP expression within the targeted tumor must be incorporated into the treatment plan to optimize the thermal dose delivery and permit prediction of the overall tissue response. A treatment planning computational model capable of predicting the temperature, HSP27 and HSP70 expression, and damage fraction distributions associated with laser heating in healthy prostate tissue and tumors is presented. Measured thermally induced HSP27 and HSP70 expression kinetics and injury data for normal and cancerous prostate cells and prostate tumors are employed to create the first HSP expression predictive model and formulate an Arrhenius damage model. The correlation coefficients between measured and model predicted temperature, HSP27, and HSP70 were 0.98, 0.99, and 0.99, respectively, confirming the accuracy of the model. Utilization of the treatment planning model in the design of prostate cancer thermal therapies can enable optimization of the treatment outcome by controlling HSP expression and injury.

  15. Obesity and Prostate Cancer.

    PubMed

    Cao, Yin; Giovannucci, Edward

    Prostate cancer is a complex, heterogeneous disease. Factors related to detection, particularly PSA screening, further increase heterogeneity in the manifestation of the disease. It is thus not possible to provide a simple summary of the relationship between obesity and prostate cancer. Findings on obesity, often defined using body mass index (BMI), and total prostate cancer risk have been mixed; however, obesity is relatively consistently associated with a higher risk of aggressive prostate cancer, with aggressiveness defined in various ways (e.g., advanced stage, fatal, poorer prognosis in men with prostate cancer). Many methodologic issues (e.g., influence of PSA screening, detection bias and treatment) need to be thoroughly considered in both existing and future etiologic and prognostic research. Biological mechanisms supporting the link are under investigation, but may involve insulin and IGF axis, sex steroid hormones and alterations in metabolism. Some promising data suggest that molecular sub-types of prostate cancer may offer insights into etiology, but further study is required. A full evaluation of body fatness and weight change over the life course would not only provide insights to the underlying mechanisms but also allow more effective interventions.

  16. Prostate Cancer Pathology Resource Network

    DTIC Science & Technology

    2015-12-01

    researchers. Specimens include prostatectomy tissues (frozen, paraffin embedded, and tissue microarrays (TMAs), serum, plasma, buffy coat, prostatic fluid...Prostate Cancer, biorepository, biomarkers, tissue microarrays 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a...usage by the prostate cancer research community. The specimens in the PCBN include tissues from prostatectomies, serum, plasma, buffy coat, prostatic

  17. Optoacoustic characterization of prostate cancer in an in vivo transgenic murine model

    NASA Astrophysics Data System (ADS)

    Patterson, Michelle P.; Riley, Christopher B.; Kolios, Michael C.; Whelan, William M.

    2014-05-01

    Optoacoustic (OA) imaging was employed to distinguish normal from neoplastic tissues in a transgenic murine model of prostate cancer. OA images of five tumor-bearing mice and five age-matched controls across a 14 mm×14 mm region of interest (ROI) on the lower abdomen were acquired using a reverse-mode OA imaging system (Seno Medical Instruments Inc., San Antonio, Texas). Neoplastic prostate tissue was identified based on the OA signal amplitude in combination with spectral analysis of the OA radio frequency (RF) data. Integration of the signal amplitude images was performed to construct two-dimensional images of the ROI. The prostate tumors generated higher amplitude signals than those of the surrounding tissues, with contrast ratios ranging from 31 to 36 dB. The RF spectrum analysis showed significant differences between the tumor and the control mice. The midband fit was higher by 5 dB (62%), the intercept higher by 4 dB (57%) and the spectral slope higher by 0.4 dB/MHz (50%) for neoplastic prostate tissue compared to normal tissues in the control mice. The results demonstrate that OA offers high contrast imaging of prostate cancer in vivo.

  18. Targeting Th17-IL-17 Pathway in Prevention of Micro-Invasive Prostate Cancer in a Mouse Model.

    PubMed

    Zhang, Qiuyang; Liu, Sen; Ge, Dongxia; Cunningham, David M; Huang, Feng; Ma, Lin; Burris, Thomas P; You, Zongbing

    2017-06-01

    Chronic inflammation has been associated with the development and progression of human cancers including prostate cancer. The exact role of the inflammatory Th17-IL-17 pathway in prostate cancer remains unknown. In this study, we aimed to determine the importance of Th17 cells and IL-17 in a Pten-null prostate cancer mouse model. The Pten-null mice were treated by Th17 inhibitor SR1001 or anti-mouse IL-17 monoclonal antibody from 6 weeks of age up to 12 weeks of age. For SR1001 treatment, the mice were injected intraperitoneally (i.p.) twice a day with vehicle or SR1001, which was dissolved in a dimethylsulfoxide (DMSO) solution. All mice were euthanized for necropsy at 12 weeks of age. For IL-17 antibody treatment, the mice were injected intravenously (i.v.) once every two weeks with control IgG or rat anti-mouse IL-17 monoclonal antibody, which was dissolved in PBS. The injection time points were at 6, 8, and 10 weeks old. All mice were analyzed for the prostate phenotypes at 12 weeks of age. We found that either SR1001 or anti-IL-17 antibody treatment decreased the formation of micro-invasive prostate cancer in Pten-null mice. The SR1001 or anti-IL-17 antibody treated mouse prostates had reduced proliferation, increased apoptosis, and reduced angiogenesis, as well as reduced inflammatory cell infiltration. By assessing the epithelial-to-mesenchymal transition (EMT) markers, we found that SR1001 or anti-IL-17 antibody treated prostate tissues had weaker EMT phenotype compared to the control treated prostates. These results demonstrated that Th17-IL-17 pathway plays a key role in prostate cancer progression in Pten-null mice. Targeting Th17-IL-17 pathway could prevent micro-invasive prostate cancer formation in mice. Prostate 77:888-899, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  19. Slow Disease Progression in a C57BL/6 Pten-Deficient Mouse Model of Prostate Cancer

    PubMed Central

    Svensson, Robert U.; Haverkamp, Jessica M.; Thedens, Daniel R.; Cohen, Michael B.; Ratliff, Timothy L.; Henry, Michael D.

    2011-01-01

    Prostate-specific deletion of Pten in mice has been reported to recapitulate histological progression of human prostate cancer. To improve on this model, we introduced the conditional ROSA26 luciferase reporter allele to monitor prostate cancer progression via bioluminescence imaging and extensively backcrossed mice onto the albino C57BL/6 genetic background to address variability in tumor kinetics and to enhance imaging sensitivity. Bioluminescence signal increased rapidly in Ptenp−/− mice from 3 to 11 weeks, but was much slower from 11 to 52 weeks. Changes in bioluminescence signal were correlated with epithelial proliferation. Magnetic resonance imaging revealed progressive increases in prostate volume, which were attributed to excessive fluid retention in the anterior prostate and to expansion of the stroma. Development of invasive prostate cancer in 52-week-old Ptenp−/− mice was rare, indicating that disease progression was slowed relative to that in previous reports. Tumors in these mice exhibited a spontaneous inflammatory phenotype and were rapidly infiltrated by myeloid-derived suppressor cells. Although Ptenp−/− tumors responded to androgen withdrawal, they failed to exhibit relapsed growth for up to 1 year. Taken together, these data identify a mild prostate cancer phenotype in C57BL/6 prostate-specific Pten-deficient mice, reflecting effects of the C57BL/6 genetic background on cancer progression. This model provides a platform for noninvasive assessment of how genetic and environmental risk factors may affect disease progression. PMID:21703427

  20. Vitamin D, Sunlight and Prostate Cancer Risk

    PubMed Central

    Donkena, Krishna Vanaja; Young, Charles Y. F.

    2011-01-01

    Prostate cancer is the second common cancer in men worldwide. The prevention of prostate cancer remains a challenge to researchers and clinicians. Here, we review the relationship of vitamin D and sunlight to prostate cancer risk. Ultraviolet radiation of the sunlight is the main stimulator for vitamin D production in humans. Vitamin D's antiprostate cancer activities may be involved in the actions through the pathways mediated by vitamin D metabolites, vitamin D metabolizing enzymes, vitamin D receptor (VDR), and VDR-regulated genes. Although laboratory studies including the use of animal models have shown that vitamin D has antiprostate cancer properties, whether it can effectively prevent the development and/or progression of prostate cancer in humans remains to be inconclusive and an intensively studied subject. This review will provide up-to-date information regarding the recent outcomes of laboratory and epidemiology studies on the effects of vitamin D on prostate cancer prevention. PMID:21991434

  1. A model for the design and construction of a resource for the validation of prognostic prostate cancer biomarkers: the Canary Prostate Cancer Tissue Microarray

    PubMed Central

    Hawley, Sarah; Fazli, Ladan; McKenney, Jesse K.; Simko, Jeff; Troyer, Dean; Nicolas, Marlo; Newcomb, Lisa F.; Cowan, Janet E.; Crouch, Luis; Ferrari, Michelle; Hernandez, Javier; Hurtado-Coll, Antonio; Kuchinsky, Kyle; Liew, Janet; Mendez-Meza, Rosario; Smith, Elizabeth; Tenggara, Imelda; Zhang, Xiaotun; Carroll, Peter R.; Chan, June M.; Gleave, Martin; Lance, Raymond; Lin, Daniel W.; Nelson, Peter S.; Thompson, Ian M.; Feng, Ziding; True, Lawrence D.; Brooks, James D.

    2012-01-01

    Tissue microarrays provide unique resources for rapid evaluation and validation of tissue biomarkers. The Canary Foundation Retrospective Prostate Tissue Microarray Resource used a rigorous statistical design, quota sampling, a variation of the case-cohort study, to select patients for inclusion in a multicenter, retrospective prostate cancer tissue microarray cohort. The study is designed to definitively validate tissue biomarkers of prostate cancer recurrence after radical prostatectomy. Tissue samples from over 1,000 participants treated for prostate cancer with radical prostatectomy between 1995 and 2004 were selected at six participating institutions in the United States and Canada. This design captured the heterogeneity of screening and clinical practices in the contemporary North American population. Standardized clinical data were collected in a centralized database. The project has been informative in several respects. The scale and complexity of assembling tissue microarrays (TMAs) with over 200 cases at each of six sites involved unanticipated levels of effort and time. Our statistical design promises to provide a model for outcome-based studies where tissue localization methods are applied to high-density tissue microarrays. PMID:23232570

  2. Animal models of human prostate cancer: The Consensus Report of the New York Meeting of the Mouse Models of Human Cancers Consortium Prostate Pathology Committee

    PubMed Central

    Ittmann, Michael; Huang, Jiaoti; Radaelli, Enrico; Martin, Philip; Signoretti, Sabina; Sullivan, Ruth; Simons, Brian W.; Ward, Jerrold M.; Robinson, Brian D.; Chu, Gerald C.; Loda, Massimo; Thomas, George; Borowsky, Alexander; Cardiff, Robert D.

    2013-01-01

    Animal models, particularly mouse models, play a central role in the study of the etiology, prevention and treatment of human prostate cancer (PCa). While tissue culture models are extremely useful in understanding the biology of PCa, they cannot recapitulate the complex cellular interactions within the tumor microenvironment that play a key role in cancer initiation and progression. The NCI Mouse Models of Human Cancers Consortium convened a group of human and veterinary pathologists to review the current animal models of PCa and make recommendations regarding the pathological analysis of these models. Over 40 different models with 439 samples were reviewed including genetically engineered mouse models, xenograft, rat and canine models. Numerous relevant models have been developed over the last 15 years and each approach has strengths and weaknesses. Analysis of multiple genetically engineered models has shown that reactive stroma formation is present in all the models developing invasive carcinomas. In addition, numerous models with multiple genetic alterations display aggressive phenotypes characterized by sarcomatoid carcinomas and metastases, which is presumably a histological manifestation of epithelial-mesenchymal transition. The significant progress in development of improved models of PCa has already accelerated our understanding the complex biology of PCa and promises to enhance development of new approaches to prevention, detection and treatment of this common malignancy. PMID:23610450

  3. 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.

  4. Understanding your prostate cancer risk

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000931.htm Understanding your prostate cancer risk To use the sharing features on this ... enable JavaScript. Are you at risk for developing prostate cancer in your lifetime? Learn about the risk factors ...

  5. PAX2 promoted prostate cancer cell invasion through transcriptional regulation of HGF in an in vitro model.

    PubMed

    Ueda, Takashi; Ito, Saya; Shiraishi, Takumi; Taniguchi, Hidefumi; Kayukawa, Naruhiro; Nakanishi, Hiroyuki; Nakamura, Terukazu; Naya, Yoshio; Hongo, Fumiya; Kamoi, Kazumi; Okihara, Koji; Kawauchi, Akihiro; Miki, Tsuneharu

    2015-11-01

    Elucidating the mechanism of prostate cancer cell invasion may lead to the identification of novel therapeutic strategies for its treatment. Paired box 2 (PAX2) and hepatocyte growth factor (HGF) proteins are promoters of prostate cancer cell invasion. We found that PAX2 protein activated the HGF gene promoter through histone H3 acetylation and upregulated HGF gene expression. Deletion analysis revealed that the region from -637 to -314 of the HGF gene was indispensable for HGF promoter activation by PAX2. This region contains consensus PAX2 binding sequences and mutations of the sequences attenuated HGF promoter activation. Using an in vitro invasion model, we found that PAX2 and HGF promoted prostate cancer cell invasion in the same pathway. Knockdown of HGF expression attenuated the cells' invasive capacity. Moreover, in tissue samples of human prostate cancers, HGF and PAX2 expression levels were positively correlated. These results suggested that upregulation of HGF gene expression by PAX2 enhanced the invasive properties of prostate cancer cells. The PAX2/HGF pathway in prostate cancer cells may be a novel therapeutic target in prostate cancer patients.

  6. Computational Models of Anti-VEGF Therapies in Prostate Cancer

    DTIC Science & Technology

    2013-06-01

    VEGF and semaphorin ligands and receptors in prostate tumor samples to find patterns of co-regulation among these genes (Fig. 1), with comparisons to...principal component in the prostate dataset was notable due to the large negative loadings for SEMA3A , SEMA3C, SEMA3D, and SEMA3E, with a large positive...loading for NRP1 (Fig. 1). NRP1 promotes VEGF signaling, while class 3 semaphorins typically inhibit angiogenesis; thus, samples with high positive

  7. Preclinical Studies of Signaling Pathways in a Mutant Mouse Model of Hormone-Refractory Prostate Cancer

    DTIC Science & Technology

    2011-02-01

    development of prostate cancer provided the rationale for a large-scale prevention trial that evaluated the 5a-reductase inhibitor finasteride for...incidence, which has led to the recommendation of finasteride administration for men in high-risk cate- gories. As a cautionary note, however, a...Tangen CM, Parnes HL, Lippman SM, La Rosa FG, et al. 2007. Finasteride and high-grade prostate cancer in the Prostate Cancer Prevention Trial. J Natl

  8. A human GRPr-transfected Ace-1 canine prostate cancer model in mice.

    PubMed

    Ding, Haiming; Kothandaraman, Shankaran; Gong, Li; Williams, Michelle M; Dirksen, Wessel P; Rosol, Thomas J; Tweedle, Michael F

    2016-06-01

    A versatile drug screening system was developed to simplify early targeted drug discovery in mice and then translate readily from mice to a dog prostate cancer model that more fully replicates the features of human prostate cancer. We stably transfected human cDNA of the GRPr bombesin (BBN) receptor subtype to canine Ace-1 prostate cancer cells (Ace-1(huGRPr) ). Expression was examined by (125) I-Tyr(4) -BBN competition, calcium stimulation assay, and fluorescent microscopy. A dual tumor nude mouse xenograft model was developed from Ace-1(CMV) (vector transfected Ace-1) and Ace-1(huGRPr) cells. The model was used to explore the in vivo behavior of two new IRDye800-labeled GRPr binding optical imaging agents: 800-G-Abz4-t-BBN, from a GRPr agonist peptide, and 800-G-Abz4-STAT, from a GRPr antagonist peptide, by imaging the tumor mice and dissected organs. Both agents bound Ace-1(huGRPr) and PC-3, a known GRPr-expressing human prostate cancer cell line, with 4-13 nM IC50 against (125) I-Tyr(4) -BBN, but did not bind Ace-1(CMV) cells (vector transfected). Binding was blocked by bombesin. Ca(2+) activation assays demonstrated that Ace-1(huGPRr) expressed biologically active GRPr. Both Ace-1 cell lines grew in the flanks of 100% of the nude mice and formed tumors of ∼0.5 cm diameter in 1 week. In vivo imaging of the mice at 800 nm emission showed GRPr+: GRPr- tumor signal brighter by a factor of two at 24 h post IV administration of 10 nmol of the imaging agents. Blood retention (4-8% ID at 1 h) was greater by a factor >10 and cumulative urine accumulation (28-30% at 4 h) was less by a factor 2 compared to a radioactive analog of the t-BBN containing agent, (177) LuAMBA, probably due to binding to blood albumin, which we confirmed in a mouse serum assay. The dual tumor Ace-1(CMV) /Ace-1(huGRPr) model system provides a rapid test of specific to nonspecific binding of new GRPr avid agents in a model that will extend logically to the known Ace-1 orthotopic

  9. Generation of a C57BL/6 MYC-Driven Mouse Model and Cell Line of Prostate Cancer.

    PubMed

    Ellis, Leigh; Ku, ShengYu; Li, Qiuhui; Azabdaftari, Gissou; Seliski, Joseph; Olson, Brian; Netherby, Colleen S; Tang, Dean G; Abrams, Scott I; Goodrich, David W; Pili, Roberto

    2016-09-01

    Transgenic mouse modeling is a favorable tool to reflect human prostate tumorigenesis and interactions between prostate cancer and the microenvironment. The use of GEMMs and derived cell lines represent powerful tools to study prostate cancer initiation and progression with an associated tumor microenvironment. Notably, such models provide the capacity for rapid preclinical therapy studies including immune therapies for prostate cancer treatment. Backcrossing FVB Hi-MYC mice with C57BL/6N mice, we established a Hi-MYC transgenic mouse model on a C57BL/6 background (B6MYC). In addition, using a conditional reprogramming method, a novel C57BL/6 MYC driven prostate adenocarcinoma cell line was generated. Our results demonstrate that disease progression is significantly delayed in B6MYC when compared to their FVB counterparts. Current data also indicates infiltrating immune cells are present in pre-cancer lesions, prostate intraepithelial neoplasia (PIN). Further, immunophenotyping of this immune infiltrate demonstrates the predominant population as myeloid-derived suppressor cells (MDSC). Also, we successfully generated a B6MYC-CaP cell line, and determined that this new PCa cell line express markers of luminal epithelial lineage. This novel model of PCa provides a new platform to understand the cross talk between MYC driven prostate cancer and the microenvironment. Importantly, these models will be an ideal tool to support the clinical development of immunotherapy as well as other novel therapeutic strategies for prostate cancer treatment. Prostate 76:1192-1202, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Phenotype-Specific CpG Island Methylation Events in a Murine Model of Prostate Cancer

    PubMed Central

    Camoriano, Marta; Morey Kinney, Shannon R.; Moser, Michael T.; Foster, Barbara A.; Mohler, James L.; Trump, Donald L.; Karpf, Adam R.; Smiraglia, Dominic J.

    2010-01-01

    Aberrant DNA methylation plays a significant role in nearly all human cancers and may contribute to disease progression to advanced phenotypes. Study of advanced prostate cancer phenotypes in the human disease is hampered by limited availability of tissues. We therefore took advantage of the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model to study whether three different phenotypes of TRAMP tumors (PRIM, late-stage primary tumors; AIP, androgen-independent primary tumors; and MET, metastases) displayed specific patterns of CpG island hypermethylation using Restriction Landmark Genomic Scanning. Each tumor phenotype displayed numerous hypermethylation events, with the most homogeneous methylation pattern in AIP and the most heterogeneous pattern in MET. Several loci displayed a phenotype-specific methylation pattern; the most striking pattern being loci methylated at high frequency in PRIM and AIP but rarely in MET. Examination of the mRNA expression of three genes, BC058385, Goosecoid, and Neurexin 2, which exhibited nonpromoter methylation, revealed increased expression associated with downstream methylation. Only methylated samples showed mRNA expression, in which tumor phenotype was a key factor determining the level of expression. The CpG island in the human orthologue of BC058385 was methylated in human AIP but not in primary androgen-stimulated prostate cancer or benign prostate. The clinical data show a proof-of-principle that the TRAMP model can be used to identify targets of aberrant CpG island methylation relevant to human disease. In conclusion, phenotype-specific hypermethylation events were associated with the overexpression of different genes and may provide new markers of prostate tumorigenesis. PMID:18519676

  11. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1

    DTIC Science & Technology

    2010-02-01

    provide a valuable pre-clinical model for chemoprevention studies. Diets rich in either omega (ω)-3 or ω-6 polyunsaturated fatty acids ( PUFAs ) directly...polyunsaturated fatty acids ( PUFAs ), 15-lipoxygenase-1, cyclooxygenase, prostate cancer, Array, Genes. 16. SECURITY CLASSIFICATION OF: 17...FLiMP+/+ mice fed a normal diet (PIN observed) and, (3) Our study in year 2 provided mechanistic roles of omega (ω)-3 fatty acids in slowing PCa growth

  12. DWCox: A density-weighted Cox model for outlier-robust prediction of prostate cancer survival

    PubMed Central

    Xiao, Jinfeng; Wang, Sheng; Shang, Jingbo; Lin, Henry; Xin, Doris; Ren, Xiang; Han, Jiawei; Peng, Jian

    2016-01-01

    Reliable predictions on the risk and survival time of prostate cancer patients based on their clinical records can help guide their treatment and provide hints about the disease mechanism. The Cox regression is currently a commonly accepted approach for such tasks in clinical applications. More complex methods, like ensemble approaches, have the potential of reaching better prediction accuracy at the cost of increased training difficulty and worse result interpretability. Better performance on a specific data set may also be obtained by extensive manual exploration in the data space, but such developed models are subject to overfitting and usually not directly applicable to a different data set. We propose DWCox, a density-weighted Cox model that has improved robustness against outliers and thus can provide more accurate predictions of prostate cancer survival. DWCox assigns weights to the training data according to their local kernel density in the feature space, and incorporates those weights into the partial likelihood function. A linear regression is then used to predict the actual survival times from the predicted risks. In the 2015 Prostate Cancer DREAM Challenge, DWCox obtained the best average ranking in prediction accuracy on the risk and survival time. The success of DWCox is remarkable given that it is one of the smallest and most interpretable models submitted to the challenge. In simulations, DWCox performed consistently better than a standard Cox model when the training data contained many sparsely distributed outliers. Although developed for prostate cancer patients, DWCox can be easily re-trained and applied to other survival analysis problems. DWCox is implemented in R and can be downloaded from https://github.com/JinfengXiao/DWCox. PMID:28299178

  13. [Sexuality and prostate cancer].

    PubMed

    Colson, M-H; Lechevallier, E; Rambeaud, J-J; Alimi, J-C; Faix, A; Gravis, G; Hannoun-Levi, J-M; Quintens, H; Rébillard, X; Droupy, S

    2012-09-01

    All treatments of prostate cancer have a negative effect on both sexuality and male fertility. There is a specific profile of changes in the fields of quality of life, sexual, urinary, bowel and vitality according to the treatment modalities chosen. Maintain a satisfying sex is the main concern of a majority of men facing prostate cancer and its treatment. It is essential to assess the couple's sexuality before diagnosis of prostate cancer in order to deliver complete information and to consider early and appropriate treatment options at the request of the couple. Forms of sexuality sexual preference settings stored (orgasm) may, when the erection is not yet recovered, be an alternative to the couple to maintain intimacy and complicity. In all cases, a specific management and networking will in many cases to find a satisfactory sexuality. Consequences of the treatment on male fertility should be part of the information of patients with prostate cancer and their partners. The choice of treatment must take into account the desire of paternity of the couple. A semen analysis with sperm cryopreservation before any therapy should be routinely offered in men with prostate cancer, particularly among men under 55, with a partner under 43 years old or without children. If the desire for parenthood among couples, sperm cryopreservation before treatment and medical assisted reproduction are recommended.

  14. Role of Foxm1 in the Pathogenesis of Prostate Cancer

    DTIC Science & Technology

    2011-07-01

    LADY transgenic (TG) mouse models of prostate cancer . Ubiquitous over-expression of Foxm1 accelerates development of PCa, as well as significantly...types in Rosa26-Foxm1 mice, the direct role of Foxm1 in prostate epithelial cells, the cells from which prostate cancer arises, remains unknown...prostate cancer by regulating genes critical for proliferation of prostate epithelial cells and (2) that Foxm1 is negatively regulated by p19ARF tumor

  15. Functional Angiogenic Mediators in Prostate Cancer

    DTIC Science & Technology

    2001-08-01

    Prostate DAMD17-99- 1 -9521 Cancer 6. AUTHOR(S) Jennifer A. Doll, Ph.D. 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING...determine the efficacy of the natural inhibitor thrombospondin- 1 (TSP- 1 ) in treating prostate cancer in model systems. Prostate cells secrete many molecules...17-39 3 Annual Summary Report P.I. Jennifer A. Doll Award #DAMD17-99- 1 -9521 Introduction Prostate cancer is a heterogeneous disease (Cheng et al.,

  16. Detection of Prostate Cancer: Quantitative Multiparametric MR Imaging Models Developed Using Registered Correlative Histopathology.

    PubMed

    Metzger, Gregory J; Kalavagunta, Chaitanya; Spilseth, Benjamin; Bolan, Patrick J; Li, Xiufeng; Hutter, Diane; Nam, Jung W; Johnson, Andrew D; Henriksen, Jonathan C; Moench, Laura; Konety, Badrinath; Warlick, Christopher A; Schmechel, Stephen C; Koopmeiners, Joseph S

    2016-06-01

    Purpose To develop multiparametric magnetic resonance (MR) imaging models to generate a quantitative, user-independent, voxel-wise composite biomarker score (CBS) for detection of prostate cancer by using coregistered correlative histopathologic results, and to compare performance of CBS-based detection with that of single quantitative MR imaging parameters. Materials and Methods Institutional review board approval and informed consent were obtained. Patients with a diagnosis of prostate cancer underwent multiparametric MR imaging before surgery for treatment. All MR imaging voxels in the prostate were classified as cancer or noncancer on the basis of coregistered histopathologic data. Predictive models were developed by using more than one quantitative MR imaging parameter to generate CBS maps. Model development and evaluation of quantitative MR imaging parameters and CBS were performed separately for the peripheral zone and the whole gland. Model accuracy was evaluated by using the area under the receiver operating characteristic curve (AUC), and confidence intervals were calculated with the bootstrap procedure. The improvement in classification accuracy was evaluated by comparing the AUC for the multiparametric model and the single best-performing quantitative MR imaging parameter at the individual level and in aggregate. Results Quantitative T2, apparent diffusion coefficient (ADC), volume transfer constant (K(trans)), reflux rate constant (kep), and area under the gadolinium concentration curve at 90 seconds (AUGC90) were significantly different between cancer and noncancer voxels (P < .001), with ADC showing the best accuracy (peripheral zone AUC, 0.82; whole gland AUC, 0.74). Four-parameter models demonstrated the best performance in both the peripheral zone (AUC, 0.85; P = .010 vs ADC alone) and whole gland (AUC, 0.77; P = .043 vs ADC alone). Individual-level analysis showed statistically significant improvement in AUC in 82% (23 of 28) and 71% (24 of 34

  17. FGFR1-WNT-TGF-β signaling in prostate cancer mouse models recapitulates human reactive stroma

    PubMed Central

    Carstens, Julienne L.; Shahi, Payam; Van Tsang, Susan; Smith, Billie; Creighton, Chad J.; Zhang, Yiqun; Seamans, Amber; Seethammagari, Mamatha; Vedula, Indira; Levitt, Jonathan M.; Ittmann, Michael M.; Rowley, David R.; Spencer, David M.

    2014-01-01

    The reactive stroma surrounding tumor lesions performs critical roles ranging from supporting tumor cell proliferation to inducing tumorigenesis and metastasis. Therefore, it is critical to understand the cellular components and signaling control mechanisms that underlay the etiology of reactive stroma. Previous studies have individually implicated fibroblast growth factor receptor 1 (FGFR1) and canonical WNT/β-catenin signaling in prostate cancer progression and the initiation and maintenance of a reactive stroma; however, both pathways are frequently found co-activated in cancer tissue. Using autochthonous transgenic mouse models for inducible FGFR1 (JOCK1) and prostate-specific and ubiquitously expressed inducible β-catenin (Pro-Cat and Ubi-Cat, respectively) and bigenic crosses between these lines (Pro-Cat × JOCK1 and Ubi-Cat × JOCK1), we describe WNT-induced synergistic acceleration of FGFR1-driven adenocarcinoma, associated with a pronounced fibroblastic reactive stroma activation surrounding prostatic intraepithelial neoplasia (mPIN) lesions found both in situ and reconstitution assays. Both mouse and human reactive stroma exhibited increased transforming growth factor-beta (TGF-β) signaling adjacent to pathologic lesions likely contributing to invasion. Furthermore, elevated stromal TGF-β signaling was associated with higher Gleason scores in archived human biopsies, mirroring murine patterns. Our findings establish the importance of the FGFR1-WNT-TGF-β signaling axes as driving forces behind reactive stroma in aggressive prostate adenocarcinomas, deepening their relevance as therapeutic targets. PMID:24305876

  18. Promoter Hypermethylation in Prostate Cancer

    PubMed Central

    Park, Jong Y.

    2011-01-01

    Background The prostate gland is the most common site of cancer and the second leading cause of cancer mortality in American men. It is well known 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. Methods This review discusses current information on methylated genes associated with prostate cancer development and progression. Results Over 30 genes have been investigated for promoter methylation 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 reviewed. Conclusions These findings may provide new information of the pathogenesis of prostate cancer. Certain epigenetic alterations in prostate tumors are being translated into clinical practice for therapeutic use. PMID:20861812

  19. Development of New Treatments for Prostate Cancer

    SciTech Connect

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

    2005-02-01

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

  20. Risk of second primary cancer following prostate cancer radiotherapy: DVH analysis using the competitive risk model

    NASA Astrophysics Data System (ADS)

    Takam, R.; Bezak, E.; Yeoh, E. E.

    2009-02-01

    This study aimed to estimate the risk of developing second primary cancer (SPC) corresponding to various radiation treatment techniques for prostate cancer. Estimation of SPC was done by analysing differential dose-volume histograms (DDVH) of normal tissues such as rectum, bladder and urethra with the competitive risk model. Differential DVHs were obtained from treatment planning systems for external beam radiotherapy (EBRT), low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy techniques. The average risk of developing SPC was no greater than 0.6% for all treatment techniques but was lower with either LDR or HDR brachytherapy alone compared with any EBRT technique. For LDR and HDR brachytherapy alone, the risk of SPC for the rectum was 2.0 × 10-4% and 8.3 × 10-5% respectively compared with 0.2% for EBRT using five-field 3D-CRT to a total dose of 74 Gy. Overall, the risk of developing SPC for urethra following all radiation treatment techniques was very low compared with the rectum and bladder. Treatment plans which deliver equivalent doses of around 3-5 Gy to normal tissues were associated with higher risks of development of SPC.

  1. Chapter Eleven: The Drosophila Accessory Gland as a Model for Prostate Cancer and Other Pathologies

    PubMed Central

    Wilson, C.; Leiblich, A.; Goberdhan, D.C.I.; Hamdy, F.

    2017-01-01

    The human prostate is a gland of the male reproductive tract, which together with the seminal vesicles, is responsible for most seminal fluid production. It is a common site of cancer, and unlike other glands, it typically enlarges in aging men. In flies, the male accessory glands make many major seminal fluid components. Like their human equivalents, they secrete proteins from several conserved families, including proteases, lectins, and cysteine-rich secretory proteins, some of which interact with sperm and affect fertility. A key protein, sex peptide, is not conserved in vertebrates but plays a central role in mediating long-term effects on females after mating. Although postmitotic, one epithelial cell type in the accessory glands, the secondary cell, continues to grow in adults. It secretes microvesicles called exosomes from the endosomal multivesicular body, which, after mating, fuse with sperm. They also appear to affect female postmating behavior. Remarkably, the human prostate epithelium also secretes exosomes, which fuse to sperm in vitro to modulate their activity. Exosomes from prostate and other cancer cells are increasingly proposed to play fundamental roles in modulating the tumor microenvironment and in metastasis. Here we review a diverse accessory gland literature, which highlights functional analogies between the male reproductive glands of flies and humans, and a critical role for extracellular vesicles in allowing seminal fluid to promote male interests within the female. We postulate that secondary cells and prostate epithelial cells use common mechanisms to control growth, secretion, and signaling, which are relevant to prostate and other cancers, and can be genetically dissected in the uniquely tractable fly model. PMID:28057306

  2. The Drosophila Accessory Gland as a Model for Prostate Cancer and Other Pathologies.

    PubMed

    Wilson, C; Leiblich, A; Goberdhan, D C I; Hamdy, F

    2017-01-01

    The human prostate is a gland of the male reproductive tract, which together with the seminal vesicles, is responsible for most seminal fluid production. It is a common site of cancer, and unlike other glands, it typically enlarges in aging men. In flies, the male accessory glands make many major seminal fluid components. Like their human equivalents, they secrete proteins from several conserved families, including proteases, lectins, and cysteine-rich secretory proteins, some of which interact with sperm and affect fertility. A key protein, sex peptide, is not conserved in vertebrates but plays a central role in mediating long-term effects on females after mating. Although postmitotic, one epithelial cell type in the accessory glands, the secondary cell, continues to grow in adults. It secretes microvesicles called exosomes from the endosomal multivesicular body, which, after mating, fuse with sperm. They also appear to affect female postmating behavior. Remarkably, the human prostate epithelium also secretes exosomes, which fuse to sperm in vitro to modulate their activity. Exosomes from prostate and other cancer cells are increasingly proposed to play fundamental roles in modulating the tumor microenvironment and in metastasis. Here we review a diverse accessory gland literature, which highlights functional analogies between the male reproductive glands of flies and humans, and a critical role for extracellular vesicles in allowing seminal fluid to promote male interests within the female. We postulate that secondary cells and prostate epithelial cells use common mechanisms to control growth, secretion, and signaling, which are relevant to prostate and other cancers, and can be genetically dissected in the uniquely tractable fly model. © 2017 Elsevier Inc. All rights reserved.

  3. Prostate Cancer Rates by Race and Ethnicity

    MedlinePlus

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

  4. [Overdiagnosis in prostate cancer].

    PubMed

    Villeda, Christian; Gomez, Martha Olivia; Sotomayor, Mariano

    2014-06-01

    Prostate cancer screening is an absolutely controversial topic and under debate. The points of view from which the problem is analyzed also influence this issue; patient, physician and Health Care authorities have different interests that most of the times are not comprehensively analyzed. Currently, no clinical guideline supports the performance of a population screening with active recruitment, but they do support the credible information to the man who desires its performance of potential benefits and risks (opportunistic screening), as well as its performance in certain risk groups. Nevertheless, what is inherent to any screening program is the overdiagnosis of clinically irrelevant disease, which in prostate cancer has been calculated around 50%, and that, from our point of view, gives cause to the correct implementation of active surveillance programs to tamponade the potential deleterious effects of active therapies of prostate cancer.

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

    PubMed Central

    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

    2015-01-01

    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. PMID:25348195

  6. Assessing longitudinal quality of life in prostate cancer patients and their spouses: a multilevel modeling approach

    PubMed Central

    Northouse, Laurel L.; Braun, Thomas M.; Zhang, Lingling; Cimprich, Bernadine; Ronis, David L.; Mood, Darlene W.

    2013-01-01

    Purpose This study aimed at examining the relationship between quality of life (QOL) in prostate cancer (PCa) patients and partners and how baseline demographics, cancer-related factors, and time-varying psychosocial and symptom covariates affect their QOL over time. Methods Guided by a modified Stress-Coping Model, this study used multilevel modeling to analyze longitudinal data from a randomized clinical trial that tested a family-based intervention to improve QOL in couples managing PCa. Patients and partners from the usual-care control group (N = 134 dyads) independently completed the measurements at baseline, and at 4-, 8-, and 12-month follow-ups. Results Correlations of QOL between patients and partners over time were small to moderate. Patients’ lower education level, partners’ older age, higher family income, and localized cancer at baseline were associated with better QOL in couples. Over time, couples’ QOL improved as their social support and cancer-related dyadic communication increased and as couples’ uncertainty, general symptoms, and patients’ prostate cancer-related sexual and hormonal symptoms decreased. Conclusions Evidence indicates that couples’ QOL during cancer survivorship is affected by multiple contextual factors (e.g., baseline demographics and time-varying psychosocial factors and symptoms). Intervention research is needed to explore comprehensive strategies to improve couples’ QOL during the continuum of PCa survivorship. PMID:20927648

  7. Arachidonic acid metabolism in human prostate cancer

    PubMed Central

    YANG, PEIYING; CARTWRIGHT, CARRIE A.; LI, JIN; WEN, SIJIN; PROKHOROVA, INA N.; SHUREIQI, IMAD; TRONCOSO, PATRICIA; NAVONE, NORA M.; NEWMAN, ROBERT A.; KIM, JERI

    2012-01-01

    The arachidonic acid pathway is important in the development and progression of numerous malignant diseases, including prostate cancer. To more fully evaluate the role of individual cyclooxygenases (COXs), lipoxygenases (LOXs) and their metabolites in prostate cancer, we measured mRNA and protein levels of COXs and LOXs and their arachidonate metabolites in androgen-dependent (LNCaP) and androgen-independent (PC-3 and DU145) prostate cancer cell lines, bone metastasis-derived MDA PCa 2a and MDA PCa 2b cell lines and their corresponding xenograft models, as well as core biopsy specimens of primary prostate cancer and nonneoplastic prostate tissue taken ex vivo after prostatectomy. Relatively high levels of COX-2 mRNA and its product PGE2 were observed only in PC-3 cells and their xenografts. By contrast, levels of the exogenous 12-LOX product 12-HETE were consistently higher in MDA PCa 2b and PC-3 cells and their corresponding xenograft tissues than were those in LNCaP cells. More strikingly, the mean endogenous level of 12-HETE was significantly higher in the primary prostate cancers than in the nonneoplastic prostate tissue (0.094 vs. 0.010 ng/mg protein, respectively; p=0.019). Our results suggest that LOX metabolites such as 12-HETE are critical in prostate cancer progression and that the LOX pathway may be a target for treating and preventing prostate cancer. PMID:22895552

  8. Early Prostate Cancer: Hedonic Prices Model of Provider-Patient Interactions and Decisions

    SciTech Connect

    Jani, Ashesh B. Hellman, Samuel

    2008-03-15

    Purpose: To determine the relative influence of treatment features and treatment availabilities on final treatment decisions in early prostate cancer. Methods and Materials: We describe and apply a model, based on hedonic prices, to understand provider-patient interactions in prostate cancer. This model included four treatments (observation, external beam radiotherapy, brachytherapy, and prostatectomy) and five treatment features (one efficacy and four treatment complication features). We performed a literature search to estimate (1) the intersections of the 'bid' functions and 'offer' functions with the price function along different treatment feature axes, and (2) the treatments actually rendered in different patient subgroups based on age. We performed regressions to determine the relative weight of each feature in the overall interaction and the relative availability of each treatment modality to explain differences between observed vs. predicted use of different modalities in different patient subpopulations. Results: Treatment efficacy and potency preservation are the major factors influencing decisions for young patients, whereas preservation of urinary and rectal function is much more important for very elderly patients. Referral patterns seem to be responsible for most of the deviations of observed use of different treatments from those predicted by idealized provider-patient interactions. Specifically, prostatectomy is used far more commonly in young patients and radiotherapy and observation used far more commonly in elderly patients than predicted by a uniform referral pattern. Conclusions: The hedonic prices approach facilitated identifying the relative importance of treatment features and quantification of the impact of the prevailing referral pattern on prostate cancer treatment decisions.

  9. Zone-specific logistic regression models improve classification of prostate cancer on multi-parametric MRI.

    PubMed

    Dikaios, Nikolaos; Alkalbani, Jokha; Abd-Alazeez, Mohamed; Sidhu, Harbir Singh; Kirkham, Alex; Ahmed, Hashim U; Emberton, Mark; Freeman, Alex; Halligan, Steve; Taylor, Stuart; Atkinson, David; Punwani, Shonit

    2015-09-01

    To assess the interchangeability of zone-specific (peripheral-zone (PZ) and transition-zone (TZ)) multiparametric-MRI (mp-MRI) logistic-regression (LR) models for classification of prostate cancer. Two hundred and thirty-one patients (70 TZ training-cohort; 76 PZ training-cohort; 85 TZ temporal validation-cohort) underwent mp-MRI and transperineal-template-prostate-mapping biopsy. PZ and TZ uni/multi-variate mp-MRI LR-models for classification of significant cancer (any cancer-core-length (CCL) with Gleason > 3 + 3 or any grade with CCL ≥ 4 mm) were derived from the respective cohorts and validated within the same zone by leave-one-out analysis. Inter-zonal performance was tested by applying TZ models to the PZ training-cohort and vice-versa. Classification performance of TZ models for TZ cancer was further assessed in the TZ validation-cohort. ROC area-under-curve (ROC-AUC) analysis was used to compare models. The univariate parameters with the best classification performance were the normalised T2 signal (T2nSI) within the TZ (ROC-AUC = 0.77) and normalized early contrast-enhanced T1 signal (DCE-nSI) within the PZ (ROC-AUC = 0.79). Performance was not significantly improved by bi-variate/tri-variate modelling. PZ models that contained DCE-nSI performed poorly in classification of TZ cancer. The TZ model based solely on maximum-enhancement poorly classified PZ cancer. LR-models dependent on DCE-MRI parameters alone are not interchangable between prostatic zones; however, models based exclusively on T2 and/or ADC are more robust for inter-zonal application. • The ADC and T2-nSI of benign/cancer PZ are higher than benign/cancer TZ. • DCE parameters are significantly different between benign PZ and TZ, but not between cancerous PZ and TZ. • Diagnostic models containing contrast enhancement parameters have reduced performance when applied across zones.

  10. Studies of a novel photosensitizer Pd-bacteriopheophorbide (Tookad) for the prostate cancer PDT in canine model

    NASA Astrophysics Data System (ADS)

    Huang, Zheng; Chen, Qun; Brun, Pierre-Herve; Wilson, Brian C.; Scherz, Avigdor; Salomon, Yoram; Luck, David L.; Beckers, Jill; Hetzel, Fred W.

    2003-12-01

    Photodynamic therapy (PDT) mediated with vascular acting photosensitizer pd-bacteriopheophorbide (Tookad), is investigated as an alternative modality for the total ablation of prostate cancer. In vivo normal canine prostate is used as the animal model. Interstitial PDT was performed by irradiating the surgically exposed prostates with a diode laser (763 nm, 150 mW/cm) to activate the i.v. infused photosensitizer drug. The effects of two-session PDT were evaluated. The prostate and its adjacent tissues were harvested and subjected to histopathological examination. At one-week, post second-session PDT, the animals recovered well with little or no urethral complications. Prostatic urethra and prostate adjacent tissues (bladder and underlying colon) were well preserved. Two-session PDT or one single session PDT induced a similar extent of damage. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. Maximum lesion size of over 3 cm in dimension could be achieved with a single 1-cm interstitial treatment, suggesting the therapy is very effective in ablating prostatic tissue. Pharmacokinetic studies show that the photosensitizer is cleared rapidly from the circulation. In conclusion, the novel photosensitizer Tookad mediated PDT may provide an effective alternative to treat prostate cancer.

  11. Simultaneous haploinsufficiency of Pten and Trp53 tumor suppressor genes accelerates tumorigenesis in a mouse model of prostate cancer

    PubMed Central

    Couto, Suzana S.; Cao, Mei; Duarte, Paulo C.; Banach-Petrosky, Whitney; Wang, Shunyou; Romanienko, Peter; Wu, Hong; Cardiff, Robert D.; Abate-Shen, Cory; Cunha, Gerald R.

    2010-01-01

    Tumor suppressor gene PTEN is important in the initiation and progression of human prostate carcinoma, whereas the role of TP53 remains controversial. Since Pten/Trp53 double conditional knockout mice show earlier onset and fast progression of prostate cancer when compared to Pten knockout mice, we asked whether heterozygosity of these two tumor suppressor genes was sufficient to accelerate prostatic tumorigenesis. To answer this question we examined prostatic lesion progression of Pten/Trp53 double heterozygous mice and a series of controls such as Pten heterozygous, Pten conditional knockout, Trp53 heterozygous and Trp53 knockout mice. Tissue recombination of adult prostatic epithelium coupled with embryonic rat seminal vesicle mesenchyme was used as a tool to stimulate prostatic epithelial proliferation. In our study, high-grade prostatic intraepithelial neoplasia (PIN) was found with high frequency at 8 weeks post-tissue recombination transplantation. PIN lesions in Pten/Trp53 double heterozygous mice were more severe than those seen in Pten heterozygous alone. Furthermore, morphologic features attributable to Pten or Trp53 loss appeared to be enhanced in double heterozygous tissues. LOH analysis of Pten and Trp53 in genomic DNA collected from high-grade PIN lesions in Pten heterozygous and Pten/Trp53 double heterozygous mice showed an intact wild-type allele for both genes in all samples examined. In conclusion, simultaneous heterozygosity of Pten and Trp53 accelerates prostatic tumorigenesis in this mouse model of prostate cancer independently of loss of heterozygosity of either gene. PMID:19281769

  12. Lack of high-dose radiation mediated prostate cancer promotion and low-dose radiation adaptive response in the TRAMP mouse model.

    PubMed

    Lawrence, M D; Ormsby, R J; Blyth, B J; Bezak, E; England, G; Newman, M R; Tilley, W D; Sykes, P J

    2013-10-01

    Cancer of the prostate is a highly prevalent disease with a heterogeneous aetiology and prognosis. Current understanding of the biological mechanisms underlying the responses of prostate tissue to ionizing radiation exposure, including cancer induction, is surprisingly limited for both high- and low-dose exposures. As population exposure to radiation increases, largely through medical imaging, a better understanding of the response of the prostate to radiation exposure is required. Low-dose radiation-induced adaptive responses for increased cancer latency and decreased cancer frequency have been demonstrated in mouse models, largely for hematological cancers. This study examines the effects of high- and low-dose whole-body radiation exposure on prostate cancer development using an autochthonous mouse model of prostate cancer: TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP). TRAMP mice were exposed to single acute high (2 Gy), low (50 mGy) and repeated low (5 × 50 mGy) doses of X rays to evaluate both the potential prostate cancer promoting effects of high-dose radiation and low-dose adaptive response phenomena in this prostate cancer model. Prostate weights and histopathology were examined to evaluate gross changes in cancer development and, in mice exposed to a single 2 Gy dose, time to palpable tumor was examined. Proliferation (Ki-67), apoptosis, DNA damage (γ-H2AX) and transgene expression (large T-antigen) were examined within TRAMP prostate sections. Neither high- nor low-dose radiation-induced effects on prostate cancer progression were observed for any of the endpoints studied. Lack of observable effects of high- or low-dose radiation exposure suggests that modulation of tumorigenesis in the TRAMP model is largely resistant to such exposures. However, further study is required to better assess the effects of radiation exposure using alternative prostate cancer models that incorporate normal prostate and in those that are not driven by SV40 large T

  13. Activin type IB receptor signaling in prostate cancer cells promotes lymph node metastasis in a xenograft model

    SciTech Connect

    Nomura, Masatoshi; Tanaka, Kimitaka; Wang, Lixiang; Goto, Yutaka; Mukasa, Chizu; Ashida, Kenji; Takayanagi, Ryoichi

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer ActRIB signaling induces Snail and S100A4 expressions in prostate cancer cells. Black-Right-Pointing-Pointer The prostate cancer cell lines expressing an active form of ActRIB were established. Black-Right-Pointing-Pointer ActRIB signaling promotes EMT and lymph node metastasis in xenograft model. -- Abstract: Activin, a member of the transforming growth factor-{beta} family, has been known to be a growth and differentiating factor. Despite its pluripotent effects, the roles of activin signaling in prostate cancer pathogenesis are still unclear. In this study, we established several cell lines that express a constitutive active form of activin type IB receptor (ActRIBCA) in human prostate cancer cells, ALVA41 (ALVA-ActRIBCA). There was no apparent change in the proliferation of ALVA-ActRIBCA cells in vitro; however, their migratory ability was significantly enhanced. In a xenograft model, histological analysis revealed that the expression of Snail, a cell-adhesion-suppressing transcription factor, was dramatically increased in ALVA-ActRIBCA tumors, indicating epithelial mesenchymal transition (EMT). Finally, mice bearing ALVA-ActRIBCA cells developed multiple lymph node metastases. In this study, we demonstrated that ActRIBCA signaling can promote cell migration in prostate cancer cells via a network of signaling molecules that work together to trigger the process of EMT, and thereby aid in the aggressiveness and progression of prostate cancers.

  14. [Diet and prostate cancer].

    PubMed

    Romero Cagigal, I; Ferruelo Alonso, A; Berenguer Sánchez, A

    2003-06-01

    Prostate cancer is the first neoplasia in the United States accounting the second in cancer deaths. With all the treatments strategies in debate because of their side effects, is very important try to elucidate prevention mechanisms that may be implicate in the development of this disease, between these, nutrients have been of mayor importance. In the present review we tried to study the most important nutritional factors implicated in the development and prevention of prostate carcinoma. We focus our attention over the polyphenols of the red wine, which influence over cellular proliferation and apoptosis in LNCaP cells have been studied in our Department.

  15. Using a Novel Transgenic Mouse Model to Study c-Myc Oncogenic Pathway in Castration Resistance and Chemoresistance of Prostate Cancer

    DTIC Science & Technology

    2014-10-01

    model for tumor of epididymis together with prostate tumor. Tumor of epididymis is a rare type of cancer in human, and most of them are benign . The...Oncogenic Pathway in Castration Resistance and Chemoresistance of Prostate Cancer PRINCIPAL INVESTIGATOR: Feng Yang, Ph.D. CONTRACTING...CONTRACT NUMBER Using a Novel Transgenic Mouse Model to Study c-Myc Oncogenic Pathway in Castration Resistance and Chemoresistance of Prostate Cancer

  16. Simulated prostate biopsy: prostate cancer distribution and clinical correlation

    NASA Astrophysics Data System (ADS)

    Bauer, John J.; Zeng, Jianchao; Zhang, Wei; Sesterhenn, Isabell A.; Dean, Robert; Moul, Judd W.; Mun, Seong K.

    2000-04-01

    Our group has recently obtained data based upon whole- mounted step-sectioned radical prostatectomy specimens using a 3D computer assisted prostate biopsy simulator that suggests an increased detection rate is possible using laterally placed biopsies. A new 10-core biopsy pattern was demonstrated to be superior to the traditional sextant biopsy. This patter includes the traditional sextant biopsy cores and four laterally placed biopsies in the right and left apex and mid portion of the prostate gland. The objective of this study is to confirm the higher prostate cancer defection rate obtained using our simulated 10-core biopsy pattern in a small clinical trial. We retrospectively reviewed 35 consecutive patients with a pathologic diagnosis of prostate cancer biopsied by a single urologist using the 10-core prostate biopsy patterns were compared with respect to prostate cancer detection rate. Of the 35 patients diagnosed with prostate cancer, 54.3 percent were diagnosed when reviewing the sextant biopsy data only. Review of the 10-core pattern revealed that an additional 45.7 percent were diagnosed when reviewing the sextant biopsy data only. Review of the 10-core pattern revealed that an additional 45.7 percent of patients were diagnosed solely with the laterally placed biopsies. Our results suggest that biopsy protocols that use laterally placed biopsies based upon a five region anatomical model are superior to the routinely used sextant prostate biopsy pattern.

  17. American Cancer Society Recommendations for Prostate Cancer Early Detection

    MedlinePlus

    ... Prostate Cancer Prevention and Early Detection American Cancer Society Recommendations for Prostate Cancer Early Detection The American Cancer Society (ACS) recommends that men have a chance to ...

  18. Can Mathematical Models Predict the Outcomes of Prostate Cancer Patients Undergoing Intermittent Androgen Deprivation Therapy?

    NASA Astrophysics Data System (ADS)

    Everett, R. A.; Packer, A. M.; Kuang, Y.

    2014-04-01

    Androgen deprivation therapy is a common treatment for advanced or metastatic prostate cancer. Like the normal prostate, most tumors depend on androgens for proliferation and survival but often develop treatment resistance. Hormonal treatment causes many undesirable side effects which significantly decrease the quality of life for patients. Intermittently applying androgen deprivation in cycles reduces the total duration with these negative effects and may reduce selective pressure for resistance. We extend an existing model which used measurements of patient testosterone levels to accurately fit measured serum prostate specific antigen (PSA) levels. We test the model's predictive accuracy, using only a subset of the data to find parameter values. The results are compared with those of an existing piecewise linear model which does not use testosterone as an input. Since actual treatment protocol is to re-apply therapy when PSA levels recover beyond some threshold value, we develop a second method for predicting the PSA levels. Based on a small set of data from seven patients, our results showed that the piecewise linear model produced slightly more accurate results while the two predictive methods are comparable. This suggests that a simpler model may be more beneficial for a predictive use compared to a more biologically insightful model, although further research is needed in this field prior to implementing mathematical models as a predictive method in a clinical setting. Nevertheless, both models are an important step in this direction.

  19. Can Mathematical Models Predict the Outcomes of Prostate Cancer Patients Undergoing Intermittent Androgen Deprivation Therapy?

    NASA Astrophysics Data System (ADS)

    Everett, R. A.; Packer, A. M.; Kuang, Y.

    Androgen deprivation therapy is a common treatment for advanced or metastatic prostate cancer. Like the normal prostate, most tumors depend on androgens for proliferation and survival but often develop treatment resistance. Hormonal treatment causes many undesirable side effects which significantly decrease the quality of life for patients. Intermittently applying androgen deprivation in cycles reduces the total duration with these negative effects and may reduce selective pressure for resistance. We extend an existing model which used measurements of patient testosterone levels to accurately fit measured serum prostate specific antigen (PSA) levels. We test the model's predictive accuracy, using only a subset of the data to find parameter values. The results are compared with those of an existing piecewise linear model which does not use testosterone as an input. Since actual treatment protocol is to re-apply therapy when PSA levels recover beyond some threshold value, we develop a second method for predicting the PSA levels. Based on a small set of data from seven patients, our results showed that the piecewise linear model produced slightly more accurate results while the two predictive methods are comparable. This suggests that a simpler model may be more beneficial for a predictive use compared to a more biologically insightful model, although further research is needed in this field prior to implementing mathematical models as a predictive method in a clinical setting. Nevertheless, both models are an important step in this direction.

  20. Clinical and Experimental Progression of a New Model of Human Prostate Cancer and Therapeutic Approach

    PubMed Central

    de Pinieux, Gonzague; Legrier, Marie-Emmanuelle; Poirson-Bichat, Florence; Courty, Yves; Bras-Gonçalves, Rui; Dutrillaux, Anne-Marie; Némati, Fariba; Oudard, Stéphane; Lidereau, Rosette; Broqua, Pierre; Junien, Jean-Louis; Dutrillaux, Bernard; Poupon, Marie-France

    2001-01-01

    We report the clinical evolution of a prostate cancer, metastasizing to lungs and bones, recurring locally, and escaping from anti-androgen therapy. Key event of biological progression of the patient’s tumor was the coincidence of allelic imbalance accumulation and of bone metastases occurrence. The recurrent tumor was established as the transplantable xenograft PAC120 in nude mice, where it grew locally. PAC120 displayed the same immunophenotype of the original tumor (positive for keratin, vimentin, prostatic acid phosphatase, and Leu-7) and expressed human HOXB9, HOXA4, HER-2/neu, and prostate-specific antigen genes, as detected by reverse transcriptase-polymerase chain reaction. It formed lung micrometastases detected by mRNA expression of human genes. Cytogenetic analysis demonstrated numerous alterations reflecting the tumor evolution. PAC120 was still hormone-dependent; its growth was strongly inhibited by the new gonadotropin-releasing hormone antagonist FE 200486 but weakly by gonadotropin-releasing hormone superagonist D-Trp6-luteinizing-hormone releasing hormone (decapeptyl). Tumor growth inhibition induced by anti-hormone therapy was linked to the hormone deprivation degree, more important and more stable with FE 200486 than with D-Trp6-luteinizing-hormone releasing hormone. Surgical castration of mice led to tumor regressions but did not prevent late recurrences. Transition to hormone-independent tumors was frequently associated with a mucoid differentiation or with a neuroendocrine-like pattern. Independent variations of mRNA expression of HER-2/neu and prostate-specific antigen were observed in hormone-independent tumors whereas HOXB9 gene expression was constant. In conclusion, PAC120 xenograft, a new model of hormone-dependent prostate cancer retained the progression potential of the original tumor, opening the opportunity to study the hormone dependence escape mechanism. PMID:11485933

  1. Aminomethylphosphonic acid inhibits growth and metastasis of human prostate cancer in an orthotopic xenograft mouse model

    PubMed Central

    Parajuli, Keshab Raj; Zhang, Qiuyang; Liu, Sen; You, Zongbing

    2016-01-01

    Aminomethylphosphonic acid (AMPA) has been shown to inhibit prostate cancer cell growth in vitro. The purpose of the present study was to determine if AMPA could inhibit growth and metastasis of prostate cancer in vivo. Human prostate cancer PC-3-LacZ-luciferase cells were implanted into the ventral lateral lobes of the prostate in 39 athymic Nu/Nu nude male mice. Seven days later, mice were randomized into the control group (n = 14, treated intraperitoneally with phosphate buffered saline), low dose group (n = 10, treated intraperitoneally with AMPA at 400 mg/kg body weight/day), and high dose group (n = 15, treated intraperitoneally with AMPA at 800 mg/kg body weight/day). Tumor growth and metastasis were examined every 4-7 days by bioluminescence imaging of live mice. We found that AMPA treatment significantly inhibited growth and metastasis of orthotopic xenograft prostate tumors and prolonged the survival time of the mice. AMPA treatment decreased expression of BIRC2 and activated caspase 3, leading to increased apoptosis in the prostate tumors. AMPA treatment decreased expression of cyclin D1. AMPA treatment also reduced angiogenesis in the prostate tumors. Taken together, these results demonstrate that AMPA can inhibit prostate cancer growth and metastasis, suggesting that AMPA may be developed into a therapeutic agent for the treatment of prostate cancer. PMID:26840261

  2. Aminomethylphosphonic acid inhibits growth and metastasis of human prostate cancer in an orthotopic xenograft mouse model.

    PubMed

    Parajuli, Keshab Raj; Zhang, Qiuyang; Liu, Sen; You, Zongbing

    2016-03-01

    Aminomethylphosphonic acid (AMPA) has been shown to inhibit prostate cancer cell growth in vitro. The purpose of the present study was to determine if AMPA could inhibit growth and metastasis of prostate cancer in vivo. Human prostate cancer PC-3-LacZ-luciferase cells were implanted into the ventral lateral lobes of the prostate in 39 athymic Nu/Nu nude male mice. Seven days later, mice were randomized into the control group (n = 14, treated intraperitoneally with phosphate buffered saline), low dose group (n = 10, treated intraperitoneally with AMPA at 400 mg/kg body weight/day), and high dose group (n = 15, treated intraperitoneally with AMPA at 800 mg/kg body weight/day). Tumor growth and metastasis were examined every 4-7 days by bioluminescence imaging of live mice. We found that AMPA treatment significantly inhibited growth and metastasis of orthotopic xenograft prostate tumors and prolonged the survival time of the mice. AMPA treatment decreased expression of BIRC2 and activated caspase 3, leading to increased apoptosis in the prostate tumors. AMPA treatment decreased expression of cyclin D1. AMPA treatment also reduced angiogenesis in the prostate tumors. Taken together, these results demonstrate that AMPA can inhibit prostate cancer growth and metastasis, suggesting that AMPA may be developed into a therapeutic agent for the treatment of prostate cancer.

  3. Tissue-scale, personalized modeling and simulation of prostate cancer growth.

    PubMed

    Lorenzo, Guillermo; Scott, Michael A; Tew, Kevin; Hughes, Thomas J R; Zhang, Yongjie Jessica; Liu, Lei; Vilanova, Guillermo; Gomez, Hector

    2016-11-29

    Recently, mathematical modeling and simulation of diseases and their treatments have enabled the prediction of clinical outcomes and the design of optimal therapies on a personalized (i.e., patient-specific) basis. This new trend in medical research has been termed "predictive medicine." Prostate cancer (PCa) is a major health problem and an ideal candidate to explore tissue-scale, personalized modeling of cancer growth for two main reasons: First, it is a small organ, and, second, tumor growth can be estimated by measuring serum prostate-specific antigen (PSA, a PCa biomarker in blood), which may enable in vivo validation. In this paper, we present a simple continuous model that reproduces the growth patterns of PCa. We use the phase-field method to account for the transformation of healthy cells to cancer cells and use diffusion-reaction equations to compute nutrient consumption and PSA production. To accurately and efficiently compute tumor growth, our simulations leverage isogeometric analysis (IGA). Our model is shown to reproduce a known shape instability from a spheroidal pattern to fingered growth. Results of our computations indicate that such shift is a tumor response to escape starvation, hypoxia, and, eventually, necrosis. Thus, branching enables the tumor to minimize the distance from inner cells to external nutrients, contributing to cancer survival and further development. We have also used our model to perform tissue-scale, personalized simulation of a PCa patient, based on prostatic anatomy extracted from computed tomography images. This simulation shows tumor progression similar to that seen in clinical practice.

  4. Tissue-scale, personalized modeling and simulation of prostate cancer growth

    PubMed Central

    Lorenzo, Guillermo; Scott, Michael A.; Tew, Kevin; Hughes, Thomas J. R.; Zhang, Yongjie Jessica; Liu, Lei; Vilanova, Guillermo; Gomez, Hector

    2016-01-01

    Recently, mathematical modeling and simulation of diseases and their treatments have enabled the prediction of clinical outcomes and the design of optimal therapies on a personalized (i.e., patient-specific) basis. This new trend in medical research has been termed “predictive medicine.” Prostate cancer (PCa) is a major health problem and an ideal candidate to explore tissue-scale, personalized modeling of cancer growth for two main reasons: First, it is a small organ, and, second, tumor growth can be estimated by measuring serum prostate-specific antigen (PSA, a PCa biomarker in blood), which may enable in vivo validation. In this paper, we present a simple continuous model that reproduces the growth patterns of PCa. We use the phase-field method to account for the transformation of healthy cells to cancer cells and use diffusion−reaction equations to compute nutrient consumption and PSA production. To accurately and efficiently compute tumor growth, our simulations leverage isogeometric analysis (IGA). Our model is shown to reproduce a known shape instability from a spheroidal pattern to fingered growth. Results of our computations indicate that such shift is a tumor response to escape starvation, hypoxia, and, eventually, necrosis. Thus, branching enables the tumor to minimize the distance from inner cells to external nutrients, contributing to cancer survival and further development. We have also used our model to perform tissue-scale, personalized simulation of a PCa patient, based on prostatic anatomy extracted from computed tomography images. This simulation shows tumor progression similar to that seen in clinical practice. PMID:27856758

  5. Tissue-scale, personalized modeling and simulation of prostate cancer growth

    NASA Astrophysics Data System (ADS)

    Lorenzo, Guillermo; Scott, Michael A.; Tew, Kevin; Hughes, Thomas J. R.; Zhang, Yongjie Jessica; Liu, Lei; Vilanova, Guillermo; Gomez, Hector

    2016-11-01

    Recently, mathematical modeling and simulation of diseases and their treatments have enabled the prediction of clinical outcomes and the design of optimal therapies on a personalized (i.e., patient-specific) basis. This new trend in medical research has been termed “predictive medicine.” Prostate cancer (PCa) is a major health problem and an ideal candidate to explore tissue-scale, personalized modeling of cancer growth for two main reasons: First, it is a small organ, and, second, tumor growth can be estimated by measuring serum prostate-specific antigen (PSA, a PCa biomarker in blood), which may enable in vivo validation. In this paper, we present a simple continuous model that reproduces the growth patterns of PCa. We use the phase-field method to account for the transformation of healthy cells to cancer cells and use diffusion-reaction equations to compute nutrient consumption and PSA production. To accurately and efficiently compute tumor growth, our simulations leverage isogeometric analysis (IGA). Our model is shown to reproduce a known shape instability from a spheroidal pattern to fingered growth. Results of our computations indicate that such shift is a tumor response to escape starvation, hypoxia, and, eventually, necrosis. Thus, branching enables the tumor to minimize the distance from inner cells to external nutrients, contributing to cancer survival and further development. We have also used our model to perform tissue-scale, personalized simulation of a PCa patient, based on prostatic anatomy extracted from computed tomography images. This simulation shows tumor progression similar to that seen in clinical practice.

  6. Diffusion-weighted MRI for early detection and characterization of prostate cancer in the transgenic adenocarcinoma of the mouse prostate model.

    PubMed

    Hill, Deborah K; Kim, Eugene; Teruel, Jose R; Jamin, Yann; Widerøe, Marius; Søgaard, Caroline D; Størkersen, Øystein; Rodrigues, Daniel N; Heindl, Andreas; Yuan, Yinyin; Bathen, Tone F; Moestue, Siver A

    2016-05-01

    To improve early diagnosis of prostate cancer to aid clinical decision-making. Diffusion-weighted magnetic resonance imaging (DW-MRI) is sensitive to water diffusion throughout tissues, which correlates with Gleason score, a histological measure of prostate cancer aggressiveness. In this study the ability of DW-MRI to detect prostate cancer onset and development was evaluated in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. T2 -weighted and DW-MRI were acquired using a 7T MR scanner, 200 mm bore diameter; 10 TRAMP and 6 C57BL/6 control mice were scanned every 4 weeks from 8 weeks of age until sacrifice at 28-30 weeks. After sacrifice, the genitourinary tract was excised and sectioned for histological analysis. Histology slides registered with DW-MR images allowed for validation of DW-MR images and the apparent diffusion coefficient (ADC) as tools for cancer detection and disease stratification. An automated early assessment tool based on ADC threshold values was developed to aid cancer detection and progression monitoring. The ADC differentiated between control prostate ((1.86 ± 0.20) × 10(-3) mm(2) /s) and normal TRAMP prostate ((1.38 ± 0.10) × 10(-3) mm(2) /s) (P = 0.0001), between TRAMP prostate and well-differentiated cancer ((0.93 ± 0.18) × 10(-3) mm(2) /s) (P = 0.0006), and between well-differentiated cancer and poorly differentiated cancer ((0.63 ± 0.06) × 10(-3) mm(2) /s) (P = 0.02). DW-MRI is a tool for early detection of cancer, and discrimination between cancer stages in the TRAMP model. The incorporation of DW-MRI-based prostate cancer stratification and monitoring could increase the accuracy of preclinical trials using TRAMP mice. © 2015 Wiley Periodicals, Inc.

  7. Chemopreventative potential of the cruciferous vegetable constituent phenethyl isothiocyanate in a mouse model of prostate cancer.

    PubMed

    Powolny, Anna A; Bommareddy, Ajay; Hahm, Eun-Ryeong; Normolle, Daniel P; Beumer, Jan H; Nelson, Joel B; Singh, Shivendra V

    2011-04-06

    This study was undertaken to determine the chemopreventative efficacy of phenethyl isothiocyanate (PEITC), a bioactive constituent of many edible cruciferous vegetables, in a mouse model of prostate cancer, and to identify potential biomarker(s) associated with PEITC response. The chemopreventative activity of dietary PEITC was investigated in Transgenic Adenocarcinoma of Mouse Prostate mice that were fed a control diet or one containing 3 μmol PEITC/g (n = 21 mice per group) for 19 weeks. Dorsolateral prostate tissue sections were stained with hematoxylin and eosin for histopathologic evaluations and subjected to immunohistochemistry for analysis of cell proliferation (Ki-67 expression), autophagy (p62 and LC3 protein expression), and E-cadherin expression. Autophagosomes were visualized by transmission electron microscopy. Apoptotic bodies were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Plasma proteomics was performed by two-dimensional gel electrophoresis followed by mass spectrometry to identify potential biomarkers of PEITC activity. All statistical tests were two-sided. Administration of PEITC (3 μmol/g diet) decreased incidence (PEITC diet vs control diet, mean = 21.65 vs 57.58%, difference = -35.93%, 95% confidence interval = -45.48% to -13.10%, P = .04) as well as burden (affected area) (PEITC diet vs control diet, mean = 18.53% vs 45.01%, difference = -26.48%, 95% confidence interval = -49.78% to -3.19%, P = .02) of poorly differentiated tumors in the dorsolateral prostate of transgenic mice compared with control mice, with no toxic effects. PEITC-mediated inhibition of prostate carcinogenesis was associated with induction of autophagy and overexpression of E-cadherin in the dorsolateral prostate. However, PEITC treatment was not associated with a decrease in cellular proliferation, apoptosis induction, or inhibition of neoangiogenesis. Plasma proteomics revealed distinct changes in the expression of several

  8. The Function of Neuroendocrine Cells in Prostate Cancer

    DTIC Science & Technology

    2012-04-01

    Award Number: W81XWH-11-1-0227 TITLE: The Function of Neuroendocrine Cells in Prostate Cancer ...REPORT TYPE Annual Report 3. DATES COVERED 1 April 2011 – 31 March 2012 4. TITLE AND SUBTITLE The Function of Neuroendocrine Cells in Prostate Cancer ...initiation and progression of human prostate cancer Scope: 1) Use a pten null mouse prostate cancer model to determine if ablation of NE cells by

  9. Adipokine Genes and Prostate Cancer Risk

    PubMed Central

    Moore, Steven C.; Leitzmann, Michael F.; Albanes, Demetrius; Weinstein, Stephanie J.; Snyder, Kirk; Virtamo, Jarmo; Ahn, Jiyoung; Mayne, Susan T.; Yu, Herbert; Peters, Ulrike; Gunter, Marc J.

    2010-01-01

    Adiposity and adipocyte-derived cytokines have been implicated in prostate carcinogenesis. However, the relationship of adipokine gene variants with prostate cancer risk has not been thoroughly investigated. We therefore examined common variants of the IL6, LEP, LEPR, TNF, and ADIPOQ genes in relation to prostate cancer in a case-control study nested within a large cohort of Finnish men. The study sample consisted of 1,053 cases of prostate cancer, diagnosed over an average 11 years of follow up, and 1,053 controls matched to the cases on age, intervention group, and date of baseline blood draw. Logistic regression was used to model the relative odds of prostate cancer. We also examined genotypes in relation to serum insulin, IGF-1, and IGF-1:IGFBP-3 among 196 controls. Variant alleles at three loci (−14858A>G, −13973A>C, −13736C>A) in a potential regulatory region of the LEP gene conferred a statistically significant 20% reduced risk of prostate cancer. For example, at the −14858A>G locus, heterozygotes and homozygotes for the A allele had an odds ratio (OR) of prostate cancer of 0.76 (95% confidence interval [95% CI]= 0.62, 0.93) and 0.79 (95% CI = 0.60, 1.04), respectively. At 13288G>A, relative to the GG genotype, the AA genotype was associated with a suggestive increased risk of prostate cancer (OR = 1.29; 95% CI, 0.99,1.67; P-trend = 0.05). Polymorphisms in the IL6, LEPR, TNF, and ADIPOQ genes were not associated with prostate cancer. Allelic variants in the LEP gene are related to prostate cancer risk, supporting a role for leptin in prostate carcinogenesis. PMID:19035456

  10. Vitamin E and Prostate Cancer

    USDA-ARS?s Scientific Manuscript database

    Vitamin E, its metabolites or its analogs, might help prevent prostate cancer initiation or progression. Prostate cancer is the most common non-skin malignancy and the second leading cause of cancer deaths among men in the United States, exceeded only by lung cancer. About 218,890 new cases of prost...

  11. Percentage of Positive Biopsy Cores: A Better Risk Stratification Model for Prostate Cancer?

    SciTech Connect

    Huang Jiayi; Vicini, Frank A.; Williams, Scott G.; Ye Hong; McGrath, Samuel; Ghilezan, Mihai; Krauss, Daniel; Martinez, Alvaro A.; Kestin, Larry L.

    2012-07-15

    Purpose: To assess the prognostic value of the percentage of positive biopsy cores (PPC) and perineural invasion in predicting the clinical outcomes after radiotherapy (RT) for prostate cancer and to explore the possibilities to improve on existing risk-stratification models. Methods and Materials: Between 1993 and 2004, 1,056 patients with clinical Stage T1c-T3N0M0 prostate cancer, who had four or more biopsy cores sampled and complete biopsy core data available, were treated with external beam RT, with or without a high-dose-rate brachytherapy boost at William Beaumont Hospital. The median follow-up was 7.6 years. Multivariate Cox regression analysis was performed with PPC, Gleason score, pretreatment prostate-specific antigen, T stage, PNI, radiation dose, androgen deprivation, age, prostate-specific antigen frequency, and follow-up duration. A new risk stratification (PPC classification) was empirically devised to incorporate PPC and replace the T stage. Results: On multivariate Cox regression analysis, the PPC was an independent predictor of distant metastasis, cause-specific survival, and overall survival (all p < .05). A PPC >50% was associated with significantly greater distant metastasis (hazard ratio, 4.01; 95% confidence interval, 1.86-8.61), and its independent predictive value remained significant with or without androgen deprivation therapy (all p < .05). In contrast, PNI and T stage were only predictive for locoregional recurrence. Combining the PPC ({<=}50% vs. >50%) with National Comprehensive Cancer Network risk stratification demonstrated added prognostic value of distant metastasis for the intermediate-risk (hazard ratio, 5.44; 95% confidence interval, 1.78-16.6) and high-risk (hazard ratio, 4.39; 95% confidence interval, 1.70-11.3) groups, regardless of the use of androgen deprivation and high-dose RT (all p < .05). The proposed PPC classification appears to provide improved stratification of the clinical outcomes relative to the National

  12. [Grading of prostate cancer].

    PubMed

    Kristiansen, G; Roth, W; Helpap, B

    2016-07-01

    The current grading of prostate cancer is based on the classification system of the International Society of Urological Pathology (ISUP) following a consensus conference in Chicago in 2014. The foundations are based on the frequently modified grading system of Gleason. This article presents a brief description of the development to the current ISUP grading system.

  13. Prostate Cancer for the Internist.

    PubMed

    Jaiswal, Shikha; Sarmad, Rehan; Arora, Sumant; Dasaraju, Radhikha; Sarmad, Komal

    2015-10-01

    In the United States, approximately 240,000 men are diagnosed annually with prostate cancer. Although effective treatment options are available for clinically localized cancer, the potential burdensome co-morbidities and attendant healthcare costs from over diagnosis and over treatment have escalated the discussion and controversy regarding appropriate screening, diagnosis, and optimal management of prostate cancer. Although the lifetime risk of developing prostate cancer is approximately 1 in 6 (~16%), the risk of dying from the disease is only ~2%. The discrepancy between the cancer incidence and lethality has led to widespread scrutiny of prostate cancer patient management, particularly for low-grade, low-stage (indolent) disease. The vast majority of men diagnosed with clinically localized prostate cancer are treated with interventional therapies despite studies demonstrating that even without treatment, prostate cancer-specific mortality is low. A MedLine/PubMed search was performed using PICO format (Patient, Intervention, Comparison and Outcome) identifying all relevant articles. No restrictions were used for publication dates. The terms "Prostate Cancer", "Screening", "Mortality", "Morbidity" yielded 307 results. "Diagnosis", "Prognosis" and "Survival" yielded 1504 results. Further filters were applied to narrow down the results using keywords "Prostate cancer screening guidelines 2014", "Beyond PSA", "NCCN Guidelines prostate", "MRI guided Prostate biopsy" yielding 72, 274, 54 and 568 results respectively. Of these, approximately 137 articles were found relevant and were reviewed. References from the reviewed articles were included in the final article.

  14. Novel 3D co-culture model for epithelial-stromal cells interaction in prostate cancer.

    PubMed

    Fang, Xiaolan; Sittadjody, Sivanandane; Gyabaah, Kenneth; Opara, Emmanuel C; Balaji, Kethandapatti C

    2013-01-01

    Paracrine function is a major mechanism of cell-cell communication within tissue microenvironment in normal development and disease. In vitro cell culture models simulating tissue or tumor microenvironment are necessary tools to delineate epithelial-stromal interactions including paracrine function, yet an ideal three-dimensional (3D) tumor model specifically studying paracrine function is currently lacking. In order to fill this void we developed a novel 3D co-culture model in double-layered alginate hydrogel microspheres, incorporating prostate cancer epithelial and stromal cells in separate compartments of the microspheres. The cells remained confined and viable within their respective spheres for over 30 days. As a proof of principle regarding paracrine function of the model, we measured shedded component of E-cadherin (sE-cad) in the conditioned media, a major membrane bound cell adhesive molecule that is highly dysregulated in cancers including prostate cancer. In addition to demonstrating that sE-cad can be reliably quantified in the conditioned media, the time course experiments also demonstrated that the amount of sE-cad is influenced by epithelial-stromal interaction. In conclusion, the study establishes a novel 3D in vitro co-culture model that can be used to study cell-cell paracrine interaction.

  15. In vivo MRI based prostate cancer localization with random forests and auto-context model

    PubMed Central

    Qian, Chunjun; Wang, Li; Gao, Yaozong; Yousuf, Ambereen; Yang, Xiaoping; Oto, Aytekin; Shen, Dinggang

    2017-01-01

    Prostate cancer is one of the major causes of cancer death for men. Magnetic resonance (MR) imaging is being increasingly used as an important modality to localize prostate cancer. Therefore, localizing prostate cancer in MRI with automated detection methods has become an active area of research. Many methods have been proposed for this task. However, most of previous methods focused on identifying cancer only in the peripheral zone (PZ), or classifying suspicious cancer ROIs into benign tissue and cancer tissue. Few works have been done on developing a fully automatic method for cancer localization in the entire prostate region, including central gland (CG) and transition zone (TZ). In this paper, we propose a novel learning-based multi-source integration framework to directly localize prostate cancer regions from in vivo MRI. We employ random forests to effectively integrate features from multi-source images together for cancer localization. Here, multi-source images include initially the multi-parametric MRIs (i.e., T2, DWI, and dADC) and later also the iteratively-estimated and refined tissue probability map of prostate cancer. Experimental results on 26 real patient data show that our method can accurately localize cancerous sections. The higher section-based evaluation (SBE), combined with the ROC analysis result of individual patients, shows that the proposed method is promising for in vivo MRI based prostate cancer localization, which can be used for guiding prostate biopsy, targeting the tumor in focal therapy planning, triage and follow-up of patients with active surveillance, as well as the decision making in treatment selection. The common ROC analysis with the AUC value of 0.832 and also the ROI-based ROC analysis with the AUC value of 0.883 both illustrate the effectiveness of our proposed method. PMID:27048995

  16. In vivo MRI based prostate cancer localization with random forests and auto-context model.

    PubMed

    Qian, Chunjun; Wang, Li; Gao, Yaozong; Yousuf, Ambereen; Yang, Xiaoping; Oto, Aytekin; Shen, Dinggang

    2016-09-01

    Prostate cancer is one of the major causes of cancer death for men. Magnetic resonance (MR) imaging is being increasingly used as an important modality to localize prostate cancer. Therefore, localizing prostate cancer in MRI with automated detection methods has become an active area of research. Many methods have been proposed for this task. However, most of previous methods focused on identifying cancer only in the peripheral zone (PZ), or classifying suspicious cancer ROIs into benign tissue and cancer tissue. Few works have been done on developing a fully automatic method for cancer localization in the entire prostate region, including central gland (CG) and transition zone (TZ). In this paper, we propose a novel learning-based multi-source integration framework to directly localize prostate cancer regions from in vivo MRI. We employ random forests to effectively integrate features from multi-source images together for cancer localization. Here, multi-source images include initially the multi-parametric MRIs (i.e., T2, DWI, and dADC) and later also the iteratively-estimated and refined tissue probability map of prostate cancer. Experimental results on 26 real patient data show that our method can accurately localize cancerous sections. The higher section-based evaluation (SBE), combined with the ROC analysis result of individual patients, shows that the proposed method is promising for in vivo MRI based prostate cancer localization, which can be used for guiding prostate biopsy, targeting the tumor in focal therapy planning, triage and follow-up of patients with active surveillance, as well as the decision making in treatment selection. The common ROC analysis with the AUC value of 0.832 and also the ROI-based ROC analysis with the AUC value of 0.883 both illustrate the effectiveness of our proposed method.

  17. Using a Novel Transgenic Mouse Model to Study c-Myc Oncogenic Pathway in Castration Resistance and Chemoresistance of Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    limited our ability to directly use it to study prostate cancer , therapy response and therapy resistance. Figure 4. H&E and IHC staining of the...our PB-Cre4/Ai-Myc/p53loxP/loxP mice to model prostate cancer , and therapy response and resistance as we have proposed in Major Tasks 2 and 3...Chemoresistance of Prostate Cancer PRINCIPAL INVESTIGATOR: Feng Yang, Ph.D. CONTRACTING ORGANIZATION: Baylor College of Medicine Houston, TX

  18. 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

  19. 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

  20. Evidence for Feedback Regulation Following Cholesterol Lowering Therapy in a Prostate Cancer Xenograft Model.

    PubMed

    Masko, Elizabeth M; Alfaqih, Mahmoud A; Solomon, Keith R; Barry, William T; Newgard, Christopher B; Muehlbauer, Michael J; Valilis, Nikolaos A; Phillips, Tameika E; Poulton, Susan H; Freedland, Alexis R; Sun, Stephanie; Dambal, Shweta K; Sanders, Sergio E; Macias, Everardo; Freeman, Michael R; Dewhirst, Mark W; Pizzo, Salvatore V; Freedland, Stephen J

    2017-04-01

    Epidemiologic data suggest cholesterol-lowering drugs may prevent the progression of prostate cancer, but not the incidence of the disease. However, the association of combination therapy in cholesterol reduction on prostate or any cancer is unclear. In this study, we compared the effects of the cholesterol lowering drugs simvastatin and ezetimibe alone or in combination on the growth of LAPC-4 prostate cancer in vivo xenografts. Proliferation assays were conducted by MTS solution and assessed by Student's t-test. 90 male nude mice were placed on a high-cholesterol Western-diet for 7 days then injected subcutaneously with 1 × 10(5) LAPC-4 cells. Two weeks post-injection, mice were randomized to control, 11 mg/kg/day simvastatin, 30 mg/kg ezetimibe, or the combination and sacrificed 42 days post-randomization. We used a generalized linear model with the predictor variables of treatment, time, and treatment by time (i.e., interaction term) with tumor volume as the outcome variable. Total serum and tumor cholesterol were measured. Tumoral RNA was extracted and cDNA synthesized from 1 ug of total RNA for quantitative real-time PCR. Simvastatin directly reduced in vitro prostate cell proliferation in a dose-dependent, cell line-specific manner, but ezetimibe had no effect. In vivo, low continuous dosing of ezetimibe, delivered by food, or simvastatin, delivered via an osmotic pump had no effect on tumor growth compared to control mice. In contrast, dual treatment of simvastatin and ezetimibe accelerated tumor growth. Ezetimibe significantly lowered serum cholesterol by 15%, while simvastatin had no effect. Ezetimibe treatment resulted in higher tumor cholesterol. A sixfold induction of low density lipoprotein receptor mRNA was observed in ezetimibe and the combination with simvastatin versus control tumors. Systemic cholesterol lowering by ezetimibe did not slow tumor growth, nor did the cholesterol independent effects of simvastatin and the combined

  1. 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.

  2. A new proposed rodent model of chemically induced prostate carcinogenesis: distinct time-course prostate cancer progression in the dorsolateral and ventral lobes.

    PubMed

    Gonçalves, Bianca F; de Campos, Silvana G P; Zanetoni, Cristiani; Scarano, Wellerson R; Falleiros, Luiz R; Amorim, Reneé L; Góes, Rejane M; Taboga, Sebastião R

    2013-08-01

    Characterization of novel rodent models for prostate cancer studies requires evaluation of either spontaneous and carcinogen-induced tumors as well as tumor incidence in different prostatic lobes. We propose a new short-term rodent model of chemically induced prostate carcinogenesis in which prostate cancer progression occurs differentially in the dorsolateral and ventral lobes. Adult gerbils were treated with MNU alone or associated with testosterone for 3 or 6 months of treatment. Tumor incidence, latency, localization, and immunohistochemistry (AR, PCNA, smooth muscle α-actin, p63, MGMT, and E-cadherin) were studied in both lobes. Comparisons between both lobes revealed that lesions developed first in the DL while the VL presented longer tumor latency. However, after 6 months, there was a dramatic increase in tumor multiplicity in the VL, mainly in MNU-treated groups. Lesions clearly progressed from a premalignant to a malignant phenotype over time and tumor latency was decreased by MNU + testosterone administration. Three-dimensional reconstruction of the prostatic complex showed that the DL developed tumors exclusively in the periurethral area and showed intense AR, PCNA, and MGMT immunostaining. Moreover, VL lesions emerged throughout the entire lobe. MNU-induced lesions presented markers indicative of an aggressive phenotype: lack of basal cells, rupture of the smooth muscle cell layer, loss of E-cadherin, and high MGMT staining. There are distinct pathways involved in tumor progression in gerbil prostate lobes. This animal provides a good model for prostate cancer since it allows the investigation of advanced steps of carcinogenesis with shorter latency periods in both lobes. Copyright © 2013 Wiley Periodicals, Inc.

  3. Inorganic Arsenic and Human Prostate Cancer

    PubMed Central

    Benbrahim-Tallaa, Lamia; Waalkes, Michael P.

    2008-01-01

    Objective We critically evaluated the etiologic role of inorganic arsenic in human prostate cancer. Data sources We assessed data from relevant epidemiologic studies concerning environmental inorganic arsenic exposure. Whole animal studies were evaluated as were in vitro model systems of inorganic arsenic carcinogenesis in the prostate. Data synthesis Multiple studies in humans reveal an association between environmental inorganic arsenic exposure and prostate cancer mortality or incidence. Many of these human studies provide clear evidence of a dose–response relationship. Relevant whole animal models showing a relationship between inorganic arsenic and prostate cancer are not available. However, cellular model systems indicate arsenic can induce malignant transformation of human prostate epithelial cells in vitro. Arsenic also appears to impact prostate cancer cell progression by precipitating events leading to androgen independence in vitro. Conclusion Available evidence in human populations and human cells in vitro indicates that the prostate is a target for inorganic arsenic carcinogenesis. A role for this common environmental contaminant in human prostate cancer initiation and/or progression would be very important. PMID:18288312

  4. Cholesterol and prostate cancer.

    PubMed

    Freeman, Michael R; Solomon, Keith R

    2004-01-01

    Cholesterol is a neutral lipid that accumulates in liquid-ordered, detergent-resistant membrane domains called lipid rafts. Lipid rafts serve as membrane platforms for signal transduction mechanisms that mediate cell growth, survival, and a variety of other processes relevant to cancer. A number of studies, going back many years, demonstrate that cholesterol accumulates in solid tumors and that cholesterol homeostasis breaks down in the prostate with aging and with the transition to the malignant state. This review summarizes the established links between cholesterol and prostate cancer (PCa), with a focus on how accumulation of cholesterol within the lipid raft component of the plasma membrane may stimulate signaling pathways that promote progression to hormone refractory disease. We propose that increases in cholesterol in prostate tumor cell membranes, resulting from increases in circulating levels or from dysregulation of endogenous synthesis, results in the coalescence of raft domains. This would have the effect of sequestering positive regulators of oncogenic signaling within rafts, while maintaining negative regulators in the liquid-disordered membrane fraction. This approach toward examining the function of lipid rafts in prostate cancer cells may provide insight into the role of circulating cholesterol in malignant growth and on the potential relationship between diet and aggressive disease. Large-scale characterization of proteins that localize to cholesterol-rich domains may help unveil signaling networks and pathways that will lead to identification of new biomarkers for disease progression and potentially to novel targets for therapeutic intervention.

  5. Prostate pathology of genetically engineered mice: definitions and classification. The consensus report from the Bar Harbor meeting of the Mouse Models of Human Cancer Consortium Prostate Pathology Committee.

    PubMed

    Shappell, Scott B; Thomas, George V; Roberts, Richard L; Herbert, Ron; Ittmann, Michael M; Rubin, Mark A; Humphrey, Peter A; Sundberg, John P; Rozengurt, Nora; Barrios, Roberto; Ward, Jerrold M; Cardiff, Robert D

    2004-03-15

    The Pathological Classification of Prostate Lesions in Genetically Engineered Mice (GEM) is the result of a directive from the National Cancer Institute Mouse Models of Human Cancer Consortium Prostate Steering Committee to provide a hierarchical taxonomy of disorders of the mouse prostate to facilitate classification of existing and newly created mouse models and the translation to human prostate pathology. The proposed Bar Harbor Classification system is the culmination of three meetings and workshops attended by various members of the Prostate Pathology Committee of the Mouse Models of Human Cancer Consortium. A 2-day Pathology Workshop was held at The Jackson Laboratory in Bar Harbor, Maine, in October 2001, in which study sets of 93 slides from 22 GEM models were provided to individual panel members. The comparison of mouse and human prostate anatomy and disease demonstrates significant differences and considerable similarities that bear on the interpretation of the origin and natural history of their diseases. The recommended classification of mouse prostate pathology is hierarchical, and includes developmental, inflammatory, benign proliferative, and neoplastic disorders. Among the neoplastic disorders, preinvasive, microinvasive, and poorly differentiated neoplasms received the most attention. Specific criteria were recommended and will be discussed. Transitions between neoplastic states were of particular concern. Preinvasive neoplasias of the mouse prostate were recognized as focal, atypical, and progressive lesions. These lesions were designated as mouse prostatic intraepithelial neoplasia (mPIN). Some atypical lesions were identified in mouse models without evidence of progression to malignancy. The panel recommended that mPIN lesions not be given histological grades, but that mPIN be further classified as to the absence or presence of documented associated progression to invasive carcinoma. Criteria for recognizing microinvasion, for classification of

  6. Tumor-targeting Salmonella typhimurium A1-R inhibits human prostate cancer experimental bone metastasis in mouse models.

    PubMed

    Toneri, Makoto; Miwa, Shinji; Zhang, Yong; Hu, Cameron; Yano, Shuya; Matsumoto, Yasunori; Bouvet, Michael; Nakanishi, Hayao; Hoffman, Robert M; Zhao, Ming

    2015-10-13

    Bone metastasis is a frequent occurrence in prostate cancer patients and often is lethal. Zoledronic acid (ZOL) is often used for bone metastasis with limited efficacy. More effective models and treatment methods are required to improve the outcome of prostate cancer patients. In the present study, the effects of tumor-targeting Salmonella typhimurium A1-R were analyzed in vitro and in vivo on prostate cancer cells and experimental bone metastasis. Both ZOL and S. typhimurium A1-R inhibited the growth of PC-3 cells expressing red fluorescent protien in vitro. To investigate the efficacy of S. typhimurium A1-R on prostate cancer experimental bone metastasis, we established models of both early and advanced stage bone metastasis. The mice were treated with ZOL, S. typhimurium A1-R, and combination therapy of both ZOL and S. typhimurium A1-R. ZOL and S. typhimurium A1-R inhibited the growth of solitary bone metastases. S. typhimurium A1-R treatment significantly decreased bone metastasis and delayed the appearance of PC-3 bone metastases of multiple mouse models. Additionally, S. typhimurium A1-R treatment significantly improved the overall survival of the mice with multiple bone metastases. The results of the present study indicate that S. typhimurium A1-R is useful to prevent and inhibit prostate cancer bone metastasis and has potential for future clinical use in the adjuvant setting.

  7. Solution formulation development and efficacy of MJC13 in a preclinical model of castration-resistant prostate cancer.

    PubMed

    Liang, Su; Bian, Xiaomei; Liang, Dong; Sivils, Jeffrey C; Neckers, Leonard M; Cox, Marc B; Xie, Huan

    2016-01-01

    MJC13, a novel FKBP52 targeting agent, has potential use for the treatment of castration-resistant prostate cancer. The purpose of this work was to develop a solution formulation of MJC13, and obtain its efficacy profile in a human prostate cancer xenograft mouse model. Preformulation studies were conducted to evaluate the physicochemical properties. Co-solvent systems were evaluated for aqueous solubility and tolerance. A human prostate cancer xenograft mouse model was established by growing 22Rv1 prostate cancer cells in C.B-17 SCID mice. The optimal formulation was used to study the efficacy of MJC13 in this preclinical model of castrate-resistant prostate cancer. We found that MJC13 was stable (at least for 1 month), highly lipophilic (logP = 6.49), poorly soluble in water (0.28 µg/mL), and highly plasma protein bound (>98%). The optimal formulation consisting of PEG 400 and Tween 80 (1:1, v/v) allowed us to achieve a MJC13 concentration of 7.5 mg/mL, and tolerated an aqueous environment. After twice weekly intratumoral injection with 10 mg/kg MJC13 in this formulation for four consecutive weeks, tumor volumes were significantly reduced compared to vehicle-treated controls.

  8. Tumor-targeting Salmonella typhimurium A1-R inhibits human prostate cancer experimental bone metastasis in mouse models

    PubMed Central

    Toneri, Makoto; Miwa, Shinji; Zhang, Yong; Hu, Cameron; Yano, Shuya; Matsumoto, Yasunori; Bouvet, Michael; Nakanishi, Hayao; Hoffman, Robert M.; Zhao, Ming

    2015-01-01

    Bone metastasis is a frequent occurrence in prostate cancer patients and often is lethal. Zoledronic acid (ZOL) is often used for bone metastasis with limited efficacy. More effective models and treatment methods are required to improve the outcome of prostate cancer patients. In the present study, the effects of tumor-targeting Salmonella typhimurium A1-R were analyzed in vitro and in vivo on prostate cancer cells and experimental bone metastasis. Both ZOL and S. typhimurium A1-R inhibited the growth of PC-3 cells expressing red fluorescent protien in vitro. To investigate the efficacy of S. typhimurium A1-R on prostate cancer experimental bone metastasis, we established models of both early and advanced stage bone metastasis. The mice were treated with ZOL, S. typhimurium A1-R, and combination therapy of both ZOL and S. typhimurium A1-R. ZOL and S. typhimurium A1-R inhibited the growth of solitary bone metastases. S. typhimurium A1-R treatment significantly decreased bone metastasis and delayed the appearance of PC-3 bone metastases of multiple mouse models. Additionally, S. typhimurium A1-R treatment significantly improved the overall survival of the mice with multiple bone metastases. The results of the present study indicate that S. typhimurium A1-R is useful to prevent and inhibit prostate cancer bone metastasis and has potential for future clinical use in the adjuvant setting. PMID:26431498

  9. 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

  10. Hyper-expression of PAX2 in human metastatic prostate tumors and its role as a cancer promoter in an in vitro invasion model.

    PubMed

    Ueda, Takashi; Ito, Saya; Shiraishi, Takumi; Kulkarni, Prakash; Ueno, Akihisa; Nakagawa, Hideo; Kimura, Yasunori; Hongo, Fumiya; Kamoi, Kazumi; Kawauchi, Akihiro; Miki, Tsuneharu

    2013-09-01

    Metastasis is a consequence of many biological events, during which cancer stem cells are shifted into a malignant state. Among these events, invasion of prostate cancer cells into host tissues is possible to be assessed by means of an in vitro invasion model, and is thought to be coupled to altered expression of membrane proteins. Dysregulated functions of the factors regulating organogenesis during embryogenesis are known to facilitate metastasis of many types of cancers. PAX2 (paired box 2) is a member of the PAX transcription factor family, which regulates prostatic ductal growth and branching in organogenesis of mammalian prostates. However, the role of PAX2 in prostate cancer development remains to be determined. PAX2 expression in human prostate cancers and normal prostate epithelium were examined by quantitative RT-PCR and immunohistochemistry. Matrigel invasion assay and a gene array analysis were performed using prostate cancer cell lines transfected with either control or PAX2 siRNA. In human prostate cancers, PAX2 was hyper-expressed in metastatic cancers, but was expressed at lower levels in non-metastatic cancers. Consistent with this, PAX2 knockdown repressed cell growth and invasion in a Matrigel invasion assay. Gene ontology analysis revealed that many cell membrane proteins were downregulated after PAX2 knockdown. Our data suggested that PAX2 hyper-expression promotes the development of the metastatic state in prostate cancer cells, presumably through upregulating the expression of cell membrane proteins. Copyright © 2013 Wiley Periodicals, Inc.

  11. Docetaxel-titanate nanotubes enhance radiosensitivity in an androgen-independent prostate cancer model

    PubMed Central

    Mirjolet, Céline; Boudon, Julien; Loiseau, Alexis; Chevrier, Sandy; Boidot, Romain; Oudot, Alexandra; Collin, Bertrand; Martin, Etienne; Joy, Pattayil Alias; Millot, Nadine; Créhange, Gilles

    2017-01-01

    Around 40% of high-risk prostate cancer patients who undergo radiotherapy (RT) will experience biochemical failure. Chemotherapy, such as docetaxel (DTX), can enhance the efficacy of RT. Multidrug resistance mechanisms often limit drug efficacy by decreasing intracellular concentrations of drugs in tumor cells. It is, therefore, of interest to develop nanocarriers of DTX to maintain the drug inside cancer cells and thus improve treatment efficacy. The purpose of this study was to investigate the use of titanate nanotubes (TiONts) to develop a TiONts-DTX nanocarrier and to evaluate its radiosensitizing in vivo efficacy in a prostate cancer model. In vitro cytotoxic activity of TiONts-DTX was evaluated using an MTS assay. The biodistribution of TiONts-DTX was analyzed in vivo by single-photon emission computed tomography. The benefit of TiONts-DTX associated with RT was evaluated in vivo. Eight groups with seven mice in each were used to evaluate the efficacy of the nanohybrid combined with RT: control with buffer IT injection ± RT, free DXL ± RT, TiONts ± RT and TiONts-DXL ± RT. Mouse behavior, health status and tumor volume were monitored twice a week until the tumor volume reached a maximum of 2,000 mm3. More than 70% of nanohybrids were localized inside the tumor 96 h after administration. Tumor growth was significantly slowed by TiONts-DTX associated with RT, compared with free DTX in the same conditions (P=0.013). These results suggest that TiONts-DTX improved RT efficacy and might enhance local control in high-risk localized prostate cancer.

  12. Cryosurgical technique: assessment of the fundamental variables using human prostate cancer model systems.

    PubMed

    Klossner, Daniel P; Robilotto, Anthony T; Clarke, Dominic M; VanBuskirk, Robert G; Baust, John M; Gage, Andrew A; Baust, John G

    2007-12-01

    Cryosurgery offers a promising therapeutic alternative for the treatment of prostate cancer. While often successful, complete cryoablation of cancerous tissues sometimes fails due to technical challenges. Factors such as the end temperature, cooling rate, duration of the freezing episode, and repetition of the freezing cycle have been reported to influence cryosurgical outcome. Accordingly, we investigated the effects of these variables in an in vitro prostate cancer model. Human prostate cancer PC-3 and LNCaP cultures were exposed to a range of sub-zero temperatures (-5 to -40 degrees C), and cells were thawed followed by return to 37 degrees C. Post-thaw viability was assessed using a variety of fluorescent probes including alamarBlue (metabolic activity), calceinAM (membrane integrity), and propidium iodide (necrosis). Freeze duration following ice nucleation was investigated using single and double freezing cycles (5, 10, and 20 min). The results demonstrated that lower freezing temperatures yielded greater cell death, and that LNCaP cells were more susceptible to freezing than PC-3 cells. At -15 degrees C, PC-3 yielded approximately 55% viability versus approximately 20% viability for LNCaP. Double freezing cycles were found to be more than twice as destructive versus a single freeze-thaw cycle. Both cell types experienced increased cell death when exposed to freezing temperatures for longer durations. When thawing rates were considered, passive (slower) thawing following freezing yielded greater cell death than active (faster) thawing. A 20% difference in viability between passive and active thawing was observed for PC-3 for a 10 min freeze. Finally, the results demonstrate that just reaching -40 degrees C in vitro may not be sufficient to obtain complete cell death. The data support the use of extended freeze times, multiple freeze-thaw cycles, and passive thawing to provide maximum cell destruction.

  13. Invariant NKT Cell Ligands for Prostate Cancer Vaccines

    DTIC Science & Technology

    2011-06-01

    NUMBER Invariant NKT Cell Ligands for Prostate Cancer Vaccines 5b. GRANT NUMBER W81XWH-09-1-0156 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...efficacy in tumor bearing mice. 15. SUBJECT TERMS prostate cancer , immunotherapy, NKT cells 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...proposal have shown that mice bearing prostate cancers in the TRAMP model ( prostate specific expression on SV40 T antigen, Tag, oncogene) do not respond

  14. Prostate cancer screening using risk stratification based on a multi-state model of genetic variants.

    PubMed

    Yen, Amy Ming-Fang; Auvinen, Anssi; Schleutker, Johanna; Wu, Yi-Ying; Fann, Jean Ching-Yuan; Tammela, Teuvo; Chen, Sam Li-Sheng; Chiu, Sherry Yueh-Hsia; Chen, Hsiu-Hsi

    2015-06-01

    Risk-stratified screening for prostate cancer (PCa) with prostate-specific antigen (PSA) testing incorporating genetic variants has received some attention but has been scarcely investigated. We developed a model to stratify the Finnish population by different risk profiles related to genetic variants to optimize the screening policy. Data from the Finnish randomized controlled trial on screening for PCa with PSA testing were used to estimate a six-state Markov model of disease progression. Blood samples from Finnish men were used to assess the risk of PCa related to three genetic variants (rs4242382, rs138213197, and rs200331695). A risk score-based approach combined with a series of computer simulation models was applied to optimize individual screening policies. The 10-year risk of having progressive prostate cancer detected ranged from 43% in the top 5% risk group to approximately 11% in the bottom half of the population. Using the median group, with screening every four years beginning at 55 years-old, as the reference group, the recommended age beginning screening was approximately 47 years-old for the top 5% risk group and 55 years-old for those in the lower 60% risk group. The recommended interscreening interval has been shortened for individuals in the high risk group. The increased availability of genomic information allows the proposed multistate model to be more discriminating with respect to risk stratification and the suggested screening policy, particularly for the lowest risk groups-. -- A multi-state genetic variant-based model was developed for further application to population risk stratification to optimize the interscreening interval and the age at which to begin screening for PSA. A small sub-group of the population is likely to benefit from more intensive screening with early start and short interval, while half of the population is unlikely to benefit from such protocol (compared with four-year interval after age 55 years). © 2015 Wiley

  15. Biomarkers in Prostate Cancer Epidemiology

    PubMed Central

    Verma, Mukesh; Patel, Payal; Verma, Mudit

    2011-01-01

    Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person's genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed. PMID:24213111

  16. The Effect of Health Belief Model-Based Education on Knowledge and Prostate Cancer Screening Behaviors: A Randomized Controlled Trial

    PubMed Central

    Zare, Maryam; Ghodsbin, Fariba; Jahanbin, Iran; Ariafar, Ali; Keshavarzi, Sareh; Izadi, Tayyebe

    2016-01-01

    Background: Prostate cancer has been reported as the second leading cause of cancer death among men in 2013. Prevention and early detection of cancer are considered as critical factors in controlling the disease and increasing the survival of patients. Therefore, we aimed to investigate the effect of Health Belief Model (HBM)-based education on knowledge and prostate cancer screening behaviors in a randomized controlled trial. Methods: This study was a non-blinded randomized controlled trial. We enrolled 210 men aged 50-70. Balanced block randomization method was used to randomize the final participants who had inclusion criteria into intervention (n=93) and control (n=87) groups. The participants of the intervention group attended training workshops based on HBM. Data were collected using three questionnaires, i.e. demographic questionnaire, Prostate Cancer Screening-Health Belief Model Scale (PCS-HBMS), and the Knowledge about Prostate Cancer Screening questionnaire, all given before and immediately one month after the intervention. Results: The mean scores of the perceived susceptibility, severity, barriers and benefits increased significantly after the intervention (P>0.05) in the intervention group. In the control group, such a difference was reported only for perceived susceptibility (P>0.05). The rate of participation in prostate cancer screening in the intervention group increased from 7.5% to 24% and 43.3% one month and three months after the intervention, respectively. Conclusion: Our findings showed that the health education programs designed based on HBM could positively affect prostate cancer preventive behaviors of individuals by improving their knowledge level and leaving positive effects on perceived susceptibility and severity as well as considering the perceived barriers, benefits and health motivations. Trial Registration Number: IRCT2013090911691N3 PMID:26793731

  17. Exercise modulation of the host-tumor interaction in an orthotopic model of murine prostate cancer.

    PubMed

    Jones, Lee W; Antonelli, Jodi; Masko, Elizabeth M; Broadwater, Gloria; Lascola, Christopher D; Fels, Diane; Dewhirst, Mark W; Dyck, Jason R B; Nagendran, Jeevan; Flores, Catherine T; Betof, Allison S; Nelson, Erik R; Pollak, Michael; Dash, Rajesh C; Young, Martin E; Freedland, Stephen J

    2012-07-01

    The purpose of this study is to investigate the effects of exercise on cancer progression, metastasis, and underlying mechanisms in an orthotopic model of murine prostate cancer. C57BL/6 male mice (6-8 wk of age) were orthotopically injected with transgenic adenocarcinoma of mouse prostate C-1 cells (5 × 10(5)) and randomly assigned to exercise (n = 28) or a non-intervention control (n = 31) groups. The exercise group was given voluntary access to a wheel 24 h/day for the duration of the study. Four mice per group were serially killed on days 14, 31, and 36; the remaining 38 mice (exercise, n = 18; control, n = 20) were killed on day 53. Before death, MRI was performed to assess tumor blood perfusion. Primary tumor growth rate was comparable between groups, but expression of prometastatic genes was significantly modulated in exercising animals with a shift toward reduced metastasis. Exercise was associated with increased activity of protein kinases within the MEK/MAPK and PI3K/mTOR signaling cascades with subsequent increased intratumoral protein levels of HIF-1α and VEGF. This was associated with improved tumor vascularization. Multiplex ELISAs revealed distinct reductions in plasma concentrations of several angiogenic cytokines in the exercise group, which was associated with increased expression of angiogenic and metabolic genes in the skeletal muscle. Exercise-induced stabilization of HIF-1α and subsequent upregulation of VEGF was associated with "productive" tumor vascularization with a shift toward suppressed metastasis in an orthotopic model of prostate cancer.

  18. Exercise modulation of the host-tumor interaction in an orthotopic model of murine prostate cancer

    PubMed Central

    Antonelli, Jodi; Masko, Elizabeth M.; Broadwater, Gloria; Lascola, Christopher D.; Fels, Diane; Dewhirst, Mark W.; Dyck, Jason R. B.; Nagendran, Jeevan; Flores, Catherine T.; Betof, Allison S.; Nelson, Erik R.; Pollak, Michael; Dash, Rajesh C.; Young, Martin E.; Freedland, Stephen J.

    2012-01-01

    The purpose of this study is to investigate the effects of exercise on cancer progression, metastasis, and underlying mechanisms in an orthotopic model of murine prostate cancer. C57BL/6 male mice (6–8 wk of age) were orthotopically injected with transgenic adenocarcinoma of mouse prostate C-1 cells (5 × 105) and randomly assigned to exercise (n = 28) or a non-intervention control (n = 31) groups. The exercise group was given voluntary access to a wheel 24 h/day for the duration of the study. Four mice per group were serially killed on days 14, 31, and 36; the remaining 38 mice (exercise, n = 18; control, n = 20) were killed on day 53. Before death, MRI was performed to assess tumor blood perfusion. Primary tumor growth rate was comparable between groups, but expression of prometastatic genes was significantly modulated in exercising animals with a shift toward reduced metastasis. Exercise was associated with increased activity of protein kinases within the MEK/MAPK and PI3K/mTOR signaling cascades with subsequent increased intratumoral protein levels of HIF-1α and VEGF. This was associated with improved tumor vascularization. Multiplex ELISAs revealed distinct reductions in plasma concentrations of several angiogenic cytokines in the exercise group, which was associated with increased expression of angiogenic and metabolic genes in the skeletal muscle. Exercise-induced stabilization of HIF-1α and subsequent upregulation of VEGF was associated with “productive” tumor vascularization with a shift toward suppressed metastasis in an orthotopic model of prostate cancer. PMID:22604887

  19. Novel Prostate Cancer Pathway Modeling using Boolean Implication

    DTIC Science & Technology

    2012-09-01

    Campbell, L.L. & Polyak , K. Breast tumor heterogeneity: cancer stem cells or clonal evolution? Cell Cycle 6, 2332–2338 (2007). 6. Marusyk, A. & Polyak , K...growth and reduces tumor-initiating cell frequency. Cell Stem Cell 5, 168–177 (2009). 35. Park, S.Y., Gonen, M., Kim, H.J., Michor, F. & Polyak , K

  20. Epigenetic potential of resveratrol and analogs in preclinical models of prostate cancer

    USDA-ARS?s Scientific Manuscript database

    Prostate cancer is affected by lifestyle, particularly diet. Dietary polyphenols such as resveratrol possess anticancer properties and, therefore, chemopreventive and therapeutic potentials. Resveratrol has pleiotropic effect exerting its biological activity through multiple pathways and targets ass...

  1. 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].

  2. Methylselenium and Prostate Cancer Apoptosis

    DTIC Science & Technology

    2007-02-01

    award. Validation of these findings in animal models is currently in progress. 15. SUBJECT TERMS Selenium, methylselenol , prostate cancer...Pharmacologic inhibitors were used to manipulate caspases and c-Jun-N-terminal kinases (JNK). Results: The methylselenol precursor methylseleninic acid...Email: jlu@hi.umn.edu Methylselenol has been implicated as an active metabolite for the anticancer effect of selenium in part through the induction of

  3. Androgen receptor in prostate cancer.

    PubMed

    Heinlein, Cynthia A; Chang, Chawnshang

    2004-04-01

    The normal development and maintenance of the prostate is dependent on androgen acting through the androgen receptor (AR). AR remains important in the development and progression of prostate cancer. AR expression is maintained throughout prostate cancer progression, and the majority of androgen-independent or hormone refractory prostate cancers express AR. Mutation of AR, especially mutations that result in a relaxation of AR ligand specificity, may contribute to the progression of prostate cancer and the failure of endocrine therapy by allowing AR transcriptional activation in response to antiandrogens or other endogenous hormones. Similarly, alterations in the relative expression of AR coregulators have been found to occur with prostate cancer progression and may contribute to differences in AR ligand specificity or transcriptional activity. Prostate cancer progression is also associated with increased growth factor production and an altered response to growth factors by prostate cancer cells. The kinase signal transduction cascades initiated by mitogenic growth factors modulate the transcriptional activity of AR and the interaction between AR and AR coactivators. The inhibition of AR activity through mechanisms in addition to androgen ablation, such as modulation of signal transduction pathways, may delay prostate cancer progression.

  4. Prostate Cancer Aggressiveness Gene in Hereditary Prostate Cancer

    DTIC Science & Technology

    2007-03-01

    Ann Arbor, MI 48109-1274 REPORT DATE: March 2007 TYPE OF REPORT: Final PREPARED...REPORT DATE 01-03-2007 2. REPORT TYPE Final 3. DATES COVERED 1 Mar 2004 – 28 Feb 2007 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Prostate... inherited prostate cancer susceptibility. This statement is based on the identification of prostate cancer linkage to distal 7q markers in a recently

  5. Assessment of Tumor Stiffness With Shear Wave Elastography in a Human Prostate Cancer Xenograft Implantation Model.

    PubMed

    Wang, Yiru; Yao, Binwei; Li, Hongfei; Zhang, Yan; Gao, Hanjing; Gao, Yabin; Peng, Ruiyun; Tang, Jie

    2017-05-01

    To investigate the stiffness of human prostate cancer in a xenograft implantation model using shear wave elastography and compare the pathologic features of tumors with varying elasticity. Human prostate cancer DU-145 cells were injected into 24 nude male mice. The mice were divided into 3 groups according to the time of transplantation (6, 8, and 10 weeks). The volume, elasticity, and Young modulus of tumors were recorded by 2-dimensional sonography and shear wave elastography. The tumors were collected for pathologic analyses: hematoxylin-eosin staining, Ponceau S, and aniline staining were used to stain collagen and elastic fibers, and picric acid-sirius red staining was used to indicate type I and III collagen. The area ratios of collagen I/III were calculated. The correlation between the Young modulus of the tumor and area ratio of collagen I/III were evaluated. Immunohistochemistry of vimentin and α-smooth muscle actin was performed. Nineteen tumors in 3 groups were collected. The volume and mean Young modulus increased with the time of transplantation. There were more collagen fibers in the stiff tumors, and there were significant differences in the area ratios of collagen I/III between groups 1 (mean ± SD, 0.50 ± 0.17) and 3 (1.97 ± 0.56; P < .01). The Young modulus of the tumors showed a very significant correlation with the area ratios of collagen I/III (r = 0.968; P < .05). The expression level of α-smooth muscle actin protein was higher in group 3 than in the other groups, but differences in vimentin expression were barely seen. Shear wave elastography is a novel useful technology for showing the elasticity of human prostate cancer xenograft implantation tumors. Collagen fibers, especially collagen type I, play a crucial role in the elasticity in the human prostate cancer xenograft implantation model. © 2017 by the American Institute of Ultrasound in Medicine.

  6. The 21st Annual Prostate Cancer Foundation Scientific Retreat report.

    PubMed

    Miyahira, Andrea K; Simons, Jonathan W; Soule, Howard R

    2015-08-01

    The 21st Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held from October 23-25, 2014, in Carlsbad, CA. This event is the world's foremost scientific meeting focusing on prostate cancer and brings together leading basic, translational and clinical researchers in prostate cancer and other diverse disciplines to discuss the newest findings most likely to advance the understanding of prostate cancer and the clinical care of prostate cancer patients. This year's meeting highlighted themes including: (i) research integrity and standards for scientific reproducibility; (ii) prostate cancer disparities; (iii) mechanisms and models of prostate cancer progression and dormancy; (iv) mechanisms of therapeutic resistance; and (v) advancements in precision medicine treatments, treatment models, and predictive and prognostic biomarkers.

  7. Synergistic activity of the mTOR inhibitor ridaforolimus and the antiandrogen bicalutamide in prostate cancer models.

    PubMed

    Squillace, Rachel M; Miller, David; Wardwell, Scott D; Wang, Frank; Clackson, Tim; Rivera, Victor M

    2012-08-01

    Although androgen ablation therapy is the foundation of current prostate cancer treatment, most patients ultimately develop castration-resistant disease. One proposed mechanism to account for androgen receptor (AR) activity in the castrate environment is via crosstalk with other signaling pathways. Specifically, reciprocal interactions between the AKT/mTOR and AR pathways have been implicated in prostate cancer progression. Here, we used the potent inhibitor ridaforolimus to target mTOR signaling alone and in combination with AR blockade by bicalutamide to examine the effect of abrogating these signaling pathways. Ridaforolimus treatment inhibited the proliferation of all six prostate cancer cell lines examined with the greatest sensitivity associated with loss of PTEN and elevated AKT/mTOR pathway activity. Dual inhibition of the AR and mTOR signaling pathways provided further benefit with the ridaforolimus-bicalutamide combination producing synergistic antiproliferative effects in prostate cancer cells in vitro when compared with each agent alone. Pharmacodynamic analysis confirmed that combination treatment resulted in full inhibition of each of the respective pathways. Importantly, the ridaforolimus-bicalutamide combination exhibited potent antitumor activity with parallel reductions in plasma PSA levels in vivo. Taken together, ridaforolimus exhibited potent antiproliferative and antitumor activity in prostate cancer models and the addition of bicalutamide represents a potentially effective combination strategy for patient therapy.

  8. Synergistic activity of the mTOR inhibitor ridaforolimus and the antiandrogen bicalutamide in prostate cancer models

    PubMed Central

    SQUILLACE, RACHEL M.; MILLER, DAVID; WARDWELL, SCOTT D.; WANG, FRANK; CLACKSON, TIM; RIVERA, VICTOR M.

    2012-01-01

    Although androgen ablation therapy is the foundation of current prostate cancer treatment, most patients ultimately develop castration-resistant disease. One proposed mechanism to account for androgen receptor (AR) activity in the castrate environment is via crosstalk with other signaling pathways. Specifically, reciprocal interactions between the AKT/mTOR and AR pathways have been implicated in prostate cancer progression. Here, we used the potent inhibitor ridaforolimus to target mTOR signaling alone and in combination with AR blockade by bicalutamide to examine the effect of abrogating these signaling pathways. Ridaforolimus treatment inhibited the proliferation of all six prostate cancer cell lines examined with the greatest sensitivity associated with loss of PTEN and elevated AKT/mTOR pathway activity. Dual inhibition of the AR and mTOR signaling pathways provided further benefit with the ridaforolimus-bicalutamide combination producing synergistic antiproliferative effects in prostate cancer cells in vitro when compared with each agent alone. Pharmacodynamic analysis confirmed that combination treatment resulted in full inhibition of each of the respective pathways. Importantly, the ridaforolimus-bicalutamide combination exhibited potent anti-tumor activity with parallel reductions in plasma PSA levels in vivo. Taken together, ridaforolimus exhibited potent antiproliferative and antitumor activity in prostate cancer models and the addition of bicalutamide represents a potentially effective combination strategy for patient therapy. PMID:22614157

  9. Angiostatic Therapy: A New Treatment Modality for Prostate Cancer

    DTIC Science & Technology

    2001-07-01

    could be a new innovative treatment regimen for hormone-refractory prostate cancer. This was to be achieved with human prostate cancer tissue and...indices, low cell death and a highly invasive phenotype. Using this model we identified surgical castration, COX-2 inhibition and dendritic cell based immunotherapy as effective mono and combined therapies for prostate carcinoma.

  10. Therapeutic efficacy and molecular mechanisms of snake (Walterinnesia aegyptia) venom-loaded silica nanoparticles in the treatment of breast cancer- and prostate cancer-bearing experimental mouse models.

    PubMed

    Badr, Gamal; Al-Sadoon, Mohamed K; Rabah, Danny M

    2013-12-01

    The treatment of drug-resistant cancer is a clinical challenge, and thus screening for novel anticancer drugs is critically important. We recently demonstrated a strong enhancement of the antitumor activity of snake (Walterinnesia aegyptia) venom (WEV) in vitro in breast carcinoma, prostate cancer, and multiple myeloma cell lines but not in normal cells when the venom was combined with silica nanoparticles (WEV+NP). In the present study, we investigated the in vivo therapeutic efficacy of WEV+NP in breast cancer- and prostate cancer-bearing experimental mouse models. Xenograft breast and prostate tumor mice models were randomized into 4 groups for each cancer model (10 mice per group) and were treated with vehicle (control), NP, WEV, or WEV+NP daily for 28 days post tumor inoculation. The tumor volumes were monitored throughout the experiment. On Day 28 post tumor inoculation, breast and prostate tumor cells were collected and either directly cultured for flow cytometry analysis or lysed for Western blot and ELISA analysis. Treatment with WEV+NP or WEV alone significantly reduced both breast and prostate tumor volumes compared to treatment with NP or vehicle alone. Compared to treatment with WEV alone, treatment of breast and prostate cancer cells with WEV+NP induced marked elevations in the levels of reactive oxygen species (ROS), hydroperoxides, and nitric oxide; robust reductions in the levels of the chemokines CXCL9, CXCL10, CXCL12, CXCL13, and CXCL16 and decreased surface expression of their cognate chemokine receptors CXCR3, CXCR4, CXCR5, and CXCR6; and subsequent reductions in the chemokine-dependent migration of both breast and prostate cancer cells. Furthermore, we found that WEV+NP strongly inhibited insulin-like growth factor 1 (IGF-1)- and epidermal growth factor (EGF)-mediated proliferation of breast and prostate cancer cells, respectively, and enhanced the induction of apoptosis by increasing the activity of caspase-3,-8, and -9 in both breast and

  11. Statin Use in Prostate Cancer: An Update

    PubMed Central

    Babcook, Melissa A.; Joshi, Aditya; Montellano, Jeniece A.; Shankar, Eswar; Gupta, Sanjay

    2016-01-01

    3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known as statins, are commonly prescribed for the treatment of hypercholesterolemia and cardiovascular disease. A systematic review was conducted using the keywords “statin and prostate cancer” within the title search engines including PubMed, Web of Science, and the Cochrane Library for relevant research work published between 2004 and December 2015. Although still premature, accumulating clinical evidence suggests that statin use may be beneficial in the prevention and/or treatment of prostate cancer. These human studies consist of meta-analyses of secondary endpoints obtained from randomized, controlled cardiovascular disease clinical trials of statins, patient database, observational studies, and a few, small case–control studies, directly addressing statin use on prostate cancer pathology and recurrence. This review summarizes and discusses the recent clinical literature on statins and prostate cancer with a recommendation to move forward with randomized, placebo-controlled clinical trials, investigating the use of statins. Additional preclinical testing of statins on prostate cancer cell lines and in vivo models is needed to elucidate pathways and determine its efficacy for prevention and/or treatment of prostate cancer, more specifically, the difference in the effectiveness of lipophilic versus hydrophilic statins in prostate cancer. PMID:27441003

  12. DNA Vaccines for Prostate Cancer

    PubMed Central

    McNeel, Douglas G.; Becker, Jordan T.; Johnson, Laura E.; Olson, Brian M.

    2013-01-01

    Delivery of plasmid DNA encoding an antigen of interest has been demonstrated to be an effective means of immunization, capable of eliciting antigen-specific T cells. Plasmid DNA vaccines offer advantages over other anti-tumor vaccine approaches in terms of simplicity, manufacturing, and possibly safety. The primary disadvantage is their poor transfection efficiency and subsequent lower immunogenicity relative to other genetic vaccine approaches. However, multiple preclinical models demonstrate anti-tumor efficacy, and many efforts are underway to improve the immunogenicity and anti-tumor effect of these vaccines. Clinical trials using DNA vaccines as treatments for prostate cancer have begun, and to date have demonstrated safety and immunological effect. This review will focus on DNA vaccines as a specific means of antigen delivery, advantages and disadvantages of this type of immunization, previous experience in preclinical models and human trials specifically conducted for the treatment of prostate cancer, and future directions for the application of DNA vaccines to prostate cancer immunotherapy. PMID:24587772

  13. A novel computer based expert decision making model for prostate cancer disease management.

    PubMed

    Richman, Martin B; Forman, Ernest H; Bayazit, Yildirim; Einstein, Douglas B; Resnick, Martin I; Stovsky, Mark D

    2005-12-01

    We propose a strategic, computer based, prostate cancer decision making model based on the analytic hierarchy process. We developed a model that improves physician-patient joint decision making and enhances the treatment selection process by making this critical decision rational and evidence based. Two groups (patient and physician-expert) completed a clinical study comparing an initial disease management choice with the highest ranked option generated by the computer model. Participants made pairwise comparisons to derive priorities for the objectives and subobjectives related to the disease management decision. The weighted comparisons were then applied to treatment options to yield prioritized rank lists that reflect the likelihood that a given alternative will achieve the participant treatment goal. Aggregate data were evaluated by inconsistency ratio analysis and sensitivity analysis, which assessed the influence of individual objectives and subobjectives on the final rank list of treatment options. Inconsistency ratios less than 0.05 were reliably generated, indicating that judgments made within the model were mathematically rational. The aggregate prioritized list of treatment options was tabulated for the patient and physician groups with similar outcomes for the 2 groups. Analysis of the major defining objectives in the treatment selection decision demonstrated the same rank order for the patient and physician groups with cure, survival and quality of life being more important than controlling cancer, preventing major complications of treatment, preventing blood transfusion complications and limiting treatment cost. Analysis of subobjectives, including quality of life and sexual dysfunction, produced similar priority rankings for the patient and physician groups. Concordance between initial treatment choice and the highest weighted model option differed between the groups with the patient group having 59% concordance and the physician group having only 42

  14. The ABC model of prostate cancer: A conceptual framework for the design and interpretation of prognostic studies.

    PubMed

    Pettersson, Andreas; Gerke, Travis; Fall, Katja; Pawitan, Yudi; Holmberg, Lars; Giovannucci, Edward L; Kantoff, Philip W; Adami, Hans-Olov; Rider, Jennifer R; Mucci, Lorelei A

    2017-05-01

    There has been limited success in identifying prognostic biomarkers in prostate cancer. A partial explanation may be that insufficient emphasis has been put on clearly defining what type of marker or patient category a biomarker study aims to identify and how different cohort characteristics affect the ability to identify such a marker. In this article, the authors put forth the ABC model of prostate cancer, which defines 3 groups of patients with localized disease that an investigator may seek to identify: patients who, within a given time frame, will not develop metastases even if untreated (category A), will not develop metastases because of radical treatment (category B), or will develop metastases despite radical treatment (category C). The authors demonstrate that follow-up time and prostate-specific antigen screening intensity influence the prevalence of patients in categories A, B, and C in a study cohort, and that prognostic markers must be tested in both treated and untreated cohorts to accurately distinguish the 3 groups. The authors suggest that more emphasis should be put on considering these factors when planning, conducting, and interpreting the results from prostate cancer biomarker studies, and propose the ABC model as a framework to aid in that process. Cancer 2017;123:1490-1496. © 2017 American Cancer Society. © 2017 American Cancer Society.

  15. 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...

  16. 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...

  17. Molecular Imaging of Prostate Cancer

    PubMed Central

    Burger, Irene A.; Sala, Evis; Hricak, Hedvig; Weber, Wolfgang A.; Vargas, Hebert Alberto

    2016-01-01

    Prostate cancer is the most common noncutaneous malignancy among men in the Western world. The natural history and clinical course of prostate cancer are markedly diverse, ranging from small indolent intraprostatic lesions to highly aggressive disseminated disease. An understanding of this biologic heterogeneity is considered a necessary requisite in the quest for the adoption of precise and personalized management strategies. Molecular imaging offers the potential for noninvasive assessment of the biologic interactions underpinning prostate carcinogenesis. Currently, numerous molecular imaging probes are in clinical use or undergoing preclinical or clinical evaluation. These probes can be divided into those that image increased cell metabolism, those that target prostate cancer–specific membrane proteins and receptor molecules, and those that bind to the bone matrix adjacent to metastases to bone. The increased metabolism and vascular changes in prostate cancer cells can be evaluated with radiolabeled analogs of choline, acetate, glucose, amino acids, and nucleotides. The androgen receptor, prostate-specific membrane antigen, and gastrin-releasing peptide receptor (ie, bombesin) are overexpressed in prostate cancer and can be targeted by specific radiolabeled imaging probes. Because metastatic prostate cancer cells induce osteoblastic signaling pathways of adjacent bone tissue, bone-seeking radiotracers are sensitive tools for the detection of metastases to bone. Knowledge about the underlying biologic processes responsible for the phenotypes associated with the different stages of prostate cancer allows an appropriate choice of methods and helps avoid pitfalls. ©RSNA, 2015 PMID:26587888

  18. General Information about Prostate Cancer

    MedlinePlus

    ... problems after prostate cancer surgery include the following: Impotence . Leakage of urine from the bladder or stool ... and/or gastrointestinal cancer. Radiation therapy can cause impotence and urinary problems. Hormone therapy Hormone therapy is ...

  19. Combined AKT and MEK Pathway Blockade in Pre-Clinical Models of Enzalutamide-Resistant Prostate Cancer

    PubMed Central

    Toren, Paul; Kim, Soojin; Johnson, Fraser; Zoubeidi, Amina

    2016-01-01

    Despite recent improvements in patient outcomes using newer androgen receptor (AR) pathway inhibitors, treatment resistance in castrate resistant prostate cancer (CRPC) continues to remain a clinical problem. Co-targeting alternate resistance pathways are of significant interest to treat CRPC and delay the onset of resistance. Both the AKT and MEK signaling pathways become activated as prostate cancer develops resistance to AR-targeted therapies. This pre-clinical study explores co-targeting these pathways in AR-positive prostate cancer models. Using various in vitro models of prostate cancer disease states including androgen dependent (LNCaP), CRPC (V16D and 22RV1) and ENZ-resistant prostate cancer (MR49C and MR49F), we evaluate the relevance of targeting both AKT and MEK pathways. Our data reveal that AKT inhibition induces apoptosis and inhibits cell growth in PTEN null cell lines independently of their sensitivity to hormone therapy; however, AKT inhibition had no effect on the PTEN positive 22RV1 cell line. Interestingly, we found that MEK inhibition had greater effect on 22RV1 cells compared to LNCaP, V16D or ENZ-resistant cells MR49C and MR49F cells. In vitro, combination AKT and MEK blockade had evidence of synergy observed in some cell lines and assays, but this was not consistent across all results. In vivo, the combination of AKT and MEK inhibition resulted in more consistent tumor growth inhibition of MR49F xenografts and longer disease specific survival compared to AKT inhibitor monotherapy. As in our in vitro study, 22RV1 xenografts were more resistant to AKT inhibition while they were more sensitive to MEK inhibition. Our results suggest that targeting AKT and MEK in combination may be a valuable strategy in prostate cancer when both pathways are activated and further support the importance of characterizing the dominant oncogenic pathway in each patient’s tumor in order to select optimal therapy. PMID:27046225

  20. Development of a mathematical model that predicts the outcome of hormone therapy for prostate cancer.

    PubMed

    Hirata, Yoshito; Bruchovsky, Nicholas; Aihara, Kazuyuki

    2010-05-21

    We propose a mathematical model that quantitatively reproduces the dynamics of the serum prostate-specific antigen (PSA) level under intermittent androgen suppression (IAS) for prostate cancer. Taking into account the biological knowledge that there are reversible and irreversible changes in a malignant cell, we constructed a piecewise-linear dynamical model where the testosterone dynamics are modelled with rapid shifts between two levels, namely the normal and castrate concentrations of the male hormone. The validity of the model was supported by patient data obtained from a clinical trial of IAS. It accurately reproduced the kinetics of the therapeutic reduction of PSA and predicted the future nadir level correctly. The coexistence of reversible and irreversible changes within the malignant cell provided the best explanation of early progression to androgen independence. Finally, since the model identified patients for whom IAS was effective, it potentially offers a novel approach to individualized therapy requiring the input of time sequence values of PSA only. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  1. Urinary biomarkers for prostate cancer.

    PubMed

    Wei, John T

    2015-01-01

    The field of urology has been beset by several major trends that have affected the early detection of prostate cancer. These stem primarily from a backlash against overdiagnosis due to prostate specific antigen-based screening efforts and are epitomized by the US Preventive Services Task Force giving prostate specific antigen-based prostate cancer screening a 'D' recommendation. Consequently, the active surveillance strategy for low-risk prostate cancer has become commonplace, leading many to ask how best to follow these patients. More importantly, this public outcry has shifted the focus of early detection from an effort to diagnose any and all prostate cancers to an effort to diagnose only 'high-risk' cancer. Along with a trend for minimally invasive procedures, these forces have challenged the early detection field to more efficiently identify clinically significant prostate cancers at an early stage while limiting the number of biopsies. With US Food and Drug Administration approval, prostate cancer antigen 3 has emerged as the first bona-fide urinary biomarker for prostate cancer. Using the same platform, investigators have developed a second urinary test based on TMPRSS2:erg fusion. Recent literature supports the use of these biomarkers as a combined panel that improves risk evaluation in the setting of prostate cancer detection. Early works for applying urinary biomarkers for active surveillance are underway. Other biomarkers in the pipeline will require further prevalidation and validation work. Recent literature would support that urinary biomarkers have a clear role to supplement risk evaluation for men undergoing prostate biopsy and for prognostication.

  2. What's New in Prostate Cancer Research and Treatment?

    MedlinePlus

    ... Cancer Research? Prostate Cancer About Prostate Cancer What’s New in Prostate Cancer Research? Research into the causes, ... in many medical centers throughout the world. Genetics New research on gene changes linked to prostate cancer ...

  3. Prostate Specific Antigen and Prostate Cancer in Chinese Men Undergoing Initial Prostate Biopsies Compared with Western Cohorts.

    PubMed

    Chen, Rui; Sjoberg, Daniel D; Huang, Yiran; Xie, Liping; Zhou, Liqun; He, Dalin; Vickers, Andrew J; Sun, Yinghao

    2017-01-01

    We determined the characteristics of Chinese men undergoing initial prostate biopsy and evaluated the relationship between prostate specific antigen levels and prostate cancer/high grade prostate cancer detection in a large Chinese multicenter cohort. This retrospective study included 13,904 urology outpatients who had undergone biopsy for the indications of prostate specific antigen greater than 4.0 ng/ml or prostate specific antigen less than 4.0 ng/ml but with abnormal digital rectal examination results. The prostate specific antigen measurements were performed in accordance with the standard procedures at the respective institutions. The type of assay used was documented and recalibrated to the WHO standard. The incidence of prostate cancer and high grade prostate cancer was lower in the Chinese cohort than the Western cohorts at any given prostate specific antigen level. Around 25% of patients with a prostate specific antigen of 4.0 to 10.0 ng/ml were found to have prostate cancer compared to approximately 40% in U.S. clinical practice. Moreover, the risk curves were generally flatter than those of the Western cohorts, that is risk did not increase as rapidly with higher prostate specific antigen. The relationship between prostate specific antigen and prostate cancer risk differs importantly between Chinese and Western populations, with an overall lower risk in the Chinese cohort. Further research should explore whether environmental or genetic differences explain these findings or whether they result from unmeasured differences in screening or benign prostate disease. Caution is required for the implementation of prostate cancer clinical decision rules or prediction models for men in China or other Asian countries with similar genetic and environmental backgrounds. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  4. Health behaviour models and patient preferences regarding nutrition and physical activity after breast or prostate cancer diagnosis.

    PubMed

    Green, H J; Steinnagel, G; Morris, C; Laakso, E L

    2014-09-01

    This study aimed to improve understanding of prostate and breast cancer survivors' physical activity and nutrition and the association of these behaviours with two models. The first model, the Commonsense Self-Regulation Model (CSM), addresses cognitive and emotional perceptions of illness whereas the Transtheoretical Model (TTM) focuses on stage of readiness to engage in a behaviour. Participants who had been diagnosed with either breast (n = 145) or prostate cancer (n = 92) completed measures of demographic and health information, illness representations, stage of change, self-efficacy and preferences regarding health behaviour interventions. Health behaviours in the past seven days were measured via the International Physical Activity Questionnaire and concordance with national dietary guidelines. As hypothesised, TTM variables (stage of change and self-efficacy) demonstrated independent associations with physical activity and nutrition in regression analyses. CSM variables were not independently associated with absolute levels of health behaviours but both TTM and CSM variables were independently associated with self-reported changes in physical activity and nutrition following prostate or breast cancer diagnosis. Many participants reported high interest in receiving lifestyle interventions, particularly soon after diagnosis. Results supported application of the TTM and CSM models for strengthening behaviour change intentions and actions in breast and prostate cancer survivors. © 2014 John Wiley & Sons Ltd.

  5. Carbohydrate restriction and lactate transporter inhibition in a mouse xenograft model of human prostate cancer

    PubMed Central

    Kim, Howard S.; Masko, Elizabeth M.; Poulton, Susan L.; Kennedy, Kelly M.; Pizzo, Salvatore V.; Dewhirst, Mark W.; Freedland, Stephen J.

    2012-01-01

    OBJECTIVES To determine if a no-carbohydrate ketogenic diet (NCKD) and lactate transporter inhibition can exert a synergistic effect on delaying prostate tumour growth in a xenograft mouse model of human prostate cancer. MATERIALS AND METHODS 120 nude athymic male mice (aged 6–8 weeks) were injected s.c. in the flank with 1.0 x 105 LAPC-4 prostate cancer cells. Mice were randomized to one of four treatment groups: Western diet (WD, 35% fat, 16% protein, 49% carbohydrate) and vehicle (Veh) treatment; WD and mono-carboxylate transporter-1 (MCT1) inhibition via α-cyano-4-hydroxycinnamate (CHC) delivered through a mini osmotic pump; NCKD (84% fat, 16% protein, 0% carbohydrate) plus Veh ; or NCKD and MCT1 inhibition. Mice were fed and weighed three times per week and feed was adjusted to maintain similar body weights. Tumour size was measured twice weekly and the combined effect of treatment was tested via Kruskal – Wallis analysis of all four groups. Independent effects of treatment (NCKD vs. WD and CHC vs. Veh) on tumour volume were tested using linear regression analysis. All mice were killed on Day 53 (conclusion of pump ejection), and serum and tumour sections were analysed for various markers. Again, combined and independent effects of treatment were tested using Kruskal – Wallis and linear regression analysis, respectively. RESULTS There were no significant differences in tumour volumes among the four groups (P=0.09). When testing the independent effects of treatment, NCKD was significantly associated with lower tumour volumes at the end of the experiment (P=0.026), while CHC administration was not (P=0.981). However, CHC was associated with increased necrotic fraction (P<0.001). CONCLUSIONS Differences in tumour volumes were observed only in comparisons between mice fed a NCKD and mice fed a WD. MCT1 inhibition did not have a significant effect on tumour volume, although it was associated with increased necrotic fraction. PMID:22394625

  6. Growth Inhibition by Testosterone in an Androgen Receptor Splice Variant-Driven Prostate Cancer Model.

    PubMed

    Nakata, Daisuke; Nakayama, Kazuhide; Masaki, Tsuneo; Tanaka, Akira; Kusaka, Masami; Watanabe, Tatsuya

    2016-12-01

    Castration resistance creates a significant problem in the treatment of prostate cancer. Constitutively active splice variants of androgen receptor (AR) have emerged as drivers for resistance to androgen deprivation therapy, including the next-generation androgen-AR axis inhibitors abiraterone and enzalutamide. In this study, we describe the characteristics of a novel castration-resistant prostate cancer (CRPC) model, designated JDCaP-hr (hormone refractory). JDCaP-hr was established from an androgen-dependent JDCaP xenograft model after surgical castration. The expression of AR and its splice variants in JDCaP-hr was evaluated by immunoblotting and quantitative reverse transcription-polymerase chain reaction. The effects of AR antagonists and testosterone on JDCaP-hr were evaluated in vivo and in vitro. The roles of full-length AR (AR-FL) and AR-V7 in JDCaP-hr cell growth were evaluated using RNA interference. JDCaP-hr acquired a C-terminally truncated AR protein during progression from the parental JDCaP. The expression of AR-FL and AR-V7 mRNA was upregulated by 10-fold in JDCaP-hr compared with that in JDCaP, indicating that the JDCaP and JDCaP-hr models simulate castration resistance with some clinical features, such as overexpression of AR and its splice variants. The AR antagonist bicalutamide did not affect JDCaP-hr xenograft growth, and importantly, testosterone induced tumor regression. In vitro analysis demonstrated that androgen-independent prostate-specific antigen secretion and cell proliferation of JDCaP-hr were predominantly mediated by AR-V7. JDCaP-hr cell growth displayed a bell-shaped dependence on testosterone, and it was suppressed by physiological concentrations of testosterone. Testosterone induced rapid downregulation of both AR-FL and AR-V7 expression at physiological concentrations and suppressed expression of the AR target gene KLK3. Our findings support the clinical value of testosterone therapy, including bipolar androgen therapy, in the

  7. Targeting SRC family kinases inhibits growth and lymph node metastases of prostate cancer in an orthotopic nude mouse model.

    PubMed

    Park, Serk In; Zhang, Jing; Phillips, Kacy A; Araujo, John C; Najjar, Amer M; Volgin, Andrei Y; Gelovani, Juri G; Kim, Sun-Jin; Wang, Zhengxin; Gallick, Gary E

    2008-05-01

    Aberrant expression and/or activity of members of the Src family of nonreceptor protein tyrosine kinases (SFK) are commonly observed in progressive stages of human tumors. In prostate cancer, two SFKs (Src and Lyn) have been specifically implicated in tumor growth and progression. However, there are no data in preclinical models demonstrating potential efficacy of Src inhibitors against prostate cancer growth and/or metastasis. In this study, we used the small molecule SFK/Abl kinase inhibitor dasatinib, currently in clinical trials for solid tumors, to examine in vitro and in vivo effects of inhibiting SFKs in prostate tumor cells. In vitro, dasatinib inhibits both Src and Lyn activity, resulting in decreased cellular proliferation, migration, and invasion. In orthotopic nude mouse models, dasatinib treatment effectively inhibits expression of activated SFKs, resulting in inhibition of both tumor growth and development of lymph node metastases in both androgen-sensitive and androgen-resistant tumors. In primary tumors, SFK inhibition leads to decreased cellular proliferation (determined by immunohistochemistry for proliferating cell nuclear antigen). In vitro, small interfering RNA (siRNA)-mediated inhibition of Lyn affects cellular proliferation; siRNA inhibition of Src affects primarily cellular migration. Therefore, we conclude that SFKs are promising therapeutic targets for treatment of human prostate cancer and that Src and Lyn activities affect different cellular functions required for prostate tumor growth and progression.

  8. HOTAIR genetic variants are associated with prostate cancer and benign prostate hyperplasia in an Iranian population.

    PubMed

    Taheri, Mohammad; Habibi, Mohsen; Noroozi, Rezvan; Rakhshan, Azadeh; Sarrafzadeh, Shaghayegh; Sayad, Arezou; Omrani, Mir Davood; Ghafouri-Fard, Soudeh

    2017-05-20

    Prostate cancer and benign prostate hyperplasia (BPH) are heterogeneous disorders with a wide array of clinical presentations and high prevalence among men. Several protein coding genes as well as non-coding genes have been shown to contribute in prostate cancer and BPH risk. Among non-coding genes whose contribution in tumorigenesis has been identified is HOX transcript antisense RNA (HOTAIR). In the present study we aimed at identification of the associations between three HOTAIR polymorphisms (rs12826786, rs1899663 and rs4759314) and risk of prostate cancer and BPH by the means of tetra-primer ARMS-PCR in a population of 128 Iranian prostate cancer patients, 143 BPH patients and 250 normal male controls. The study showed that rs1899663 T allele was associated with BPH risk. Comparison between prostate cancer and BPH groups showed that rs1899663 is associated with cancer risk in co-dominant, dominant and recessive inheritance models. The rs12826786 T allele was significantly more presented in both BPH and prostate cancer groups compared with healthy subjects. This SNP was associated with both BPH and prostate cancer risk in co-dominant and recessive models. However, rs4759314 showed no significant difference in allele or genotype frequencies between three mentioned groups. In addition, some haplotypes within this gene were associated with increased prostate cancer and BPH risk. Consequently, HOTAIR can be suggested as a risk locus for prostate cancer and BPH in Iranian population. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Improving Clinical Risk Stratification at Diagnosis in Primary Prostate Cancer: A Prognostic Modelling Study

    PubMed Central

    Wright, Karen A.; Muir, Kenneth R.; Gavin, Anna

    2016-01-01

    . Using this approach, a new five-stratum risk stratification system was produced, and its prognostic power was compared against the current system, with PCSM as the outcome. The results were analysed using a Cox hazards model, the log-rank test, Kaplan-Meier curves, competing-risks regression, and concordance indices. In the training set, the new risk stratification system identified distinct subgroups with different risks of PCSM in pair-wise comparison (p < 0.0001). Specifically, the new classification identified a very low-risk group (Group 1), a subgroup of intermediate-risk cancers with a low PCSM risk (Group 2, hazard ratio [HR] 1.62 [95% CI 0.96–2.75]), and a subgroup of intermediate-risk cancers with an increased PCSM risk (Group 3, HR 3.35 [95% CI 2.04–5.49]) (p < 0.0001). High-risk cancers were also sub-classified by the new system into subgroups with lower and higher PCSM risk: Group 4 (HR 5.03 [95% CI 3.25–7.80]) and Group 5 (HR 17.28 [95% CI 11.2–26.67]) (p < 0.0001), respectively. These results were recapitulated in the testing set and remained robust after inclusion of competing risks. In comparison to the current risk stratification system, the new system demonstrated improved prognostic performance, with a concordance index of 0.75 (95% CI 0.72–0.77) versus 0.69 (95% CI 0.66–0.71) (p < 0.0001). In an external cohort, the new system achieved a concordance index of 0.79 (95% CI 0.75–0.84) for predicting PCSM versus 0.66 (95% CI 0.63–0.69) (p < 0.0001) for the current NICE risk stratification system. The main limitations of the study were that it was registry based and that follow-up was relatively short. Conclusions A novel and simple five-stratum risk stratification system outperforms the standard three-stratum risk stratification system in predicting the risk of PCSM at diagnosis in men with primary non-metastatic prostate cancer, even when accounting for competing risks. This model also allows delineation of new clinically relevant

  10. Development and validation of a logistic regression model to distinguish transition zone cancers from benign prostatic hyperplasia on multi-parametric prostate MRI.

    PubMed

    Iyama, Yuji; Nakaura, Takeshi; Katahira, Kazuhiro; Iyama, Ayumi; Nagayama, Yasunori; Oda, Seitaro; Utsunomiya, Daisuke; Yamashita, Yasuyuki

    2017-09-01

    To develop a prediction model to distinguish between transition zone (TZ) cancers and benign prostatic hyperplasia (BPH) on multi-parametric prostate magnetic resonance imaging (mp-MRI). This retrospective study enrolled 60 patients with either BPH or TZ cancer, who had undergone 3 T-MRI. We generated ten parameters for T2-weighted images (T2WI), diffusion-weighted images (DWI) and dynamic MRI. Using a t-test and multivariate logistic regression (LR) analysis to evaluate the parameters' accuracy, we developed LR models. We calculated the area under the receiver operating characteristic curve (ROC) of LR models by a leave-one-out cross-validation procedure, and the LR model's performance was compared with radiologists' performance with their opinion and with the Prostate Imaging Reporting and Data System (Pi-RADS v2) score. Multivariate LR analysis showed that only standardized T2WI signal and mean apparent diffusion coefficient (ADC) maintained their independent values (P < 0.001). The validation analysis showed that the AUC of the final LR model was comparable to that of board-certified radiologists, and superior to that of Pi-RADS scores. A standardized T2WI and mean ADC were independent factors for distinguishing between BPH and TZ cancer. The performance of the LR model was comparable to that of experienced radiologists. • It is difficult to diagnose transition zone (TZ) cancer. • We performed quantitative image analysis in multi-parametric MRI. • Standardized-T2WI and mean-ADC were independent factors for diagnosing TZ cancer. • We developed logistic-regression analysis to diagnose TZ cancer accurately. • The performance of the logistic-regression analysis was higher than PIRADSv2.

  11. Prospective Assessment of an innovative test for prostate cancer screening using the VITA process model framework.

    PubMed

    Gantner-Bär, Marion; Meier, Florian; Kolominsky-Rabas, Peter; Djanatliev, Anatoli; Metzger, Armin; Voigt, Wieland; Prokosch, Hans-Ulrich; Sedlmayr, Martin

    2014-01-01

    Healthcare innovations are crucial for enhancing patient treatment and a high-quality healthcare system. However, bringing new technologies, methods and procedures into the healthcare market is challenging. Enormous amounts of financial, personnel and organizational resources are required with no upfront certainty for the medical and economic benefit. A new and innovative approach uses interdisciplinary medical, technical and economic expertise to forecast effects of healthcare innovations already at the early research and concept phase of an idea and before major investments are made. A process model framework was developed to operationalize this structured assessment of healthcare innovations. The Visionary Iterative Tailored Approach (VITA) is based on conceptual modeling, simulation and health economics evaluation. Its application for the prospective assessment of an innovative prostate cancer screening is presented.

  12. Estimation of the optimal regime in treatment of prostate cancer recurrence from observational data using flexible weighting models.

    PubMed

    Shen, Jincheng; Wang, Lu; Taylor, Jeremy M G

    2016-11-28

    Prostate cancer patients are closely followed after the initial therapy and salvage treatment may be prescribed to prevent or delay cancer recurrence. The salvage treatment decision is usually made dynamically based on the patient's evolving history of disease status and other time-dependent clinical covariates. A multi-center prostate cancer observational study has provided us data on longitudinal prostate specific antigen (PSA) measurements, time-varying salvage treatment, and cancer recurrence time. These data enable us to estimate the best dynamic regime of salvage treatment, while accounting for the complicated confounding of time-varying covariates present in the data. A Random Forest based method is used to model the probability of regime adherence and inverse probability weights are used to account for the complexity of selection bias in regime adherence. The optimal regime is then identified by the largest restricted mean survival time. We conduct simulation studies with different PSA trends to mimic both simple and complex regime adherence mechanisms. The proposed method can efficiently accommodate complex and possibly unknown adherence mechanisms, and it is robust to cases where the proportional hazards assumption is violated. We apply the method to data collected from the observational study and estimate the best salvage treatment regime in managing the risk of prostate cancer recurrence.

  13. Self-modeling ordinal regression with time invariant covariates - An application to prostate cancer data.

    PubMed

    Shirazi, Aliakbar Mastani; Das, Kalyan; Pinheiro, Aluisio

    2015-07-28

    In a prostate cancer study, the severity of genito-urinary (bladder) toxicity is assessed for patients who were given different doses of radiation. The ordinal responses (severity of side effects) are recorded longitudinally along with the cancer stage of a patient. Differences among the patients due to time-invariant covariates are captured by the parameters. To build up a suitable framework for an analysis of such data, we propose the use of self-modeling ordinal longitudinal model where the conditional cumulative probabilities for a category of an outcome have a relation with shape-invariant model. Since patients suffering from a common disease usually exhibit a similar pattern, it is natural to build up a nonlinear model that is shape invariant. The model is essentially semi-parametric where the population time curve is modeled with penalized regression spline. Monte Carlo expectation maximization technique is used to estimate the parameters of the model. A simulation study is also carried out to justify the methodology used.

  14. Prevalence of Prostate Cancer Clinical States and Mortality in the United States: Estimates Using a Dynamic Progression Model

    PubMed Central

    Scher, Howard I.; Solo, Kirk; Valant, Jason; Todd, Mary B.; Mehra, Maneesha

    2015-01-01

    Objective To identify patient populations most in need of treatment across the prostate cancer disease continuum, we developed a novel dynamic transition model based on risk of disease progression and mortality. Design and Outcome Measurements We modeled the flow of patient populations through eight prostate cancer clinical states (PCCS) that are characterized by the status of the primary tumor, presence of metastases, prior and current treatment, and testosterone levels. Simulations used published US incidence rates for each year from 1990. Progression and mortality rates were derived from published clinical trials, meta-analyses, and observational studies. Model outputs included the incidence, prevalence, and mortality for each PCCS. The impact of novel treatments was modeled in three distinct scenarios: metastatic castration-resistant prostate cancer (mCRPC), non-metastatic CRPC (nmCRPC), or both. Results and Limitations The model estimated the prevalence of prostate cancer as 2,219,280 in the US in 2009 and 3,072,480 in 2020, and incidence of mCRPC as 36,100 and 42,970, respectively. All-cause mortality in prostate cancer was estimated at 168,290 in 2009 and 219,360 in 2020, with 20.5% and 19.5% of these deaths, respectively, occurring in men with mCRPC. The majority (86%) of incidence flow into mCRPC states was from the nmCRPC clinical state. In the scenario with novel interventions for nmCRPC states, the progression to mCRPC is reduced, thus decreasing mCRPC incidence by 12% in 2020, with a sustained decline in mCRPC mortality. A limitation of the model is that it does not estimate prostate cancer—specific mortality. Conclusion The model informs clinical trial design for prostate cancer by quantifying outcomes in PCCS, and demonstrates the impact of an effective therapy applied in an earlier clinical state of nmCRPC on the incidence of mCRPC morbidity and subsequent mortality. PMID:26460686

  15. Functional CT imaging of prostate cancer

    NASA Astrophysics Data System (ADS)

    Henderson, Elizabeth; Milosevic, Michael F.; Haider, Masoom A.; Yeung, Ivan W. T.

    2003-09-01

    The purpose of this paper is to investigate the distribution of blood flow (F), mean capillary transit time (Tc), capillary permeability (PS) and blood volume (vb) in prostate cancer using contrast-enhanced CT. Nine stage T2-T3 prostate cancer patients were enrolled in the study. Following bolus injection of a contrast agent, a time series of CT images of the prostate was acquired. Functional maps showing the distribution of F, Tc, PS and vb within the prostate were generated using a distributed parameter tracer kinetic model, the adiabatic approximation to the tissue homogeneity model. The precision of the maps was assessed using covariance matrix analysis. Finally, maps were compared to the findings of standard clinical investigations. Eight of the functional maps demonstrated regions of increased F, PS and vb, the locations of which were consistent with the results of standard clinical investigations. However, model parameters other than F could only be measured precisely within regions of high F. In conclusion functional CT images of cancer-containing prostate glands demonstrate regions of elevated F, PS and vb. However, caution should be used when applying a complex tracer kinetic model to the study of prostate cancer since not all parameters can be measured precisely in all areas.

  16. Human Prostate Cancer Hallmarks Map.

    PubMed

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

    2016-08-01

    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.

  17. Role of Nonreceptor Protein Kinase Ack1 in Prostate Cancer

    DTIC Science & Technology

    2010-05-01

    initiation and progression of prostate cancer in vivo. 15. SUBJECT TERMS Prostate cancer, transgenic mice , mouse model 16. SECURITY CLASSIFICATION OF...These transgenic mice were generated in the laboratory of our collaborator Dr. Terry Van Dyke and are a mouse model of prostate cancer in which T121...reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching

  18. Preclinical Studies of Signaling Pathways in a Mutant Mouse Model of Hormone-Refractory Prostate Cancer

    DTIC Science & Technology

    2009-02-01

    5Center for Advanced Biotechnology and Medicine and The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine... Biotechnology Inc.), according to the manufacturer’s protocol. One day after transfection, cells were treated with rapamycin and/or PD0325901 for 48 hours...and Smith, D.C. 2005. Advances in prostate cancer chemotherapy: a new era begins. CA Cancer J. Clin. 55:300–318; quiz 323–305. 6. Berry, W.R. 2005

  19. Prostate Cancer Prevention by Sulforaphane, a Novel Dietary Histone Deacetylase Inhibitor

    DTIC Science & Technology

    2009-01-01

    prostate cells (PrEC), benign prostate hyperplasia (BPH-1), early stage LNCaP cells ( androgen -dependent prostate cancer cells) and late...stage PC3 ( androgen -independent carcinoma). Treatment with 15 μM SFN caused more that 50% of cell death in prostate cancerous cells, while only...mediates epigenetic alterations and suppresses prostate cancer development in a novel APC-mutant mouse model of prostate carcinogenesis. We noticed

  20. Shared care is a model for patients with stable prostate cancer.

    PubMed

    Lund, Lars; Jønler, Morten; Graversen, Peder H; Borre, Michael; Bro, Flemming

    2013-08-01

    Patients with prostate cancer (PC) have so far been followed in specialised hospital departments after diagnosis and initiation of treatment. The main obstacles associated with the transfer of this activity to general practice include lack of experience and uncertainty as to whether general practitioners (GPs) can handle follow-up. A Steering Committee was established in collaboration with health-care professionals to devise a strategy for a shared care model. An action plan was designed that included 1) the development of a shared care model for follow-up and treatment, 2) implementation of the shared care model in cooperation between the parties involved, 3) design of procedures for re-referral, and 4) evaluation of effect, change processes and contextual factors. A total of 2,585 patients with PC were included in the study: 1,172 had disseminated disease, 754 had no recurrence after curative treatment, 244 who had been treated with a curative intent were being treated for relapse, 186 underwent watchful waiting, 135 underwent active surveillance, while other scenarios applied in the remaining 94 cases. A total of 530 patients were transferred to follow-up with a GP and 2,055 were not transferred to their GP. The main reason why patients were considered not suitable for transfer to primary health care was the patients' own desire (33%), followed by clinical or biochemical disease progression (33%). The evaluation found that 96% of the patients were very comfortable with the permanent or temporary closure of the hospital course. The project focused on factors that are essential for the successful transfer of responsibility for long-term follow-up of patients with prostate cancer. Patient transfer succeeded with high initial patient satisfaction. not relevant. not relevant.

  1. [Surgery of prostate cancer].

    PubMed

    Villers, Arnauld; Rébillard, Xavier

    2003-12-31

    Radical prostatectomy is one of the standard treatment of localised prostate cancer. It is considered that cure is obtain if PSA value is undetectable (< 0,1 ng/mL) for at least 5 to 7 years post surgery. 8 to 9 men out of 10 are currently cured by prostatectomy if the cancer is detected at organ confined stage, with PSA < 10 ng/mL. Major technical progress related to patient setting, surgical approach, instrumentation, periprostatic fascial exposure and surgical strategy clearly decreased perioperative morbidity and late effects (erectile dysfunction and incontinence). Laparoscopic approach was described mainly by French teams since 1997 and represents a validated alternative to the gold standard suprapubic open approach.

  2. 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.

  3. Molecular imaging of prostate cancer.

    PubMed

    Fox, Josef J; Schöder, Heiko; Larson, Steven M

    2012-07-01

    Prostate cancer is a complex and biologically heterogeneous disease that is not adequately assessed with conventional imaging alone. Molecular imaging with positron emission tomography (PET) is poised to fill this unmet need through noninvasive probing of the multiple molecular and cellular processes that are active in prostate cancer patients. Several PET tracers are active in early-stage and late-stage prostate cancer in humans. F18-Fluorodeoxyglucose (FDG), C11/F18-choline and sodium F18-fluoride have been studied most extensively. There is a growing body of literature supporting the utility of choline in early-stage prostate cancer. FDG and sodium F18-fluoride are more valuable in advanced disease, especially for assessing bone metastases, the prevalent form of metastases in this patient population. F18-fluorodihydrotestosterone is active in castrate disease and is emerging as a valuable pharmacodynamic marker in the development of novel androgen receptor-targeted therapies. Prostate-specific membrane antigen PET tracers are in the early stages of clinical development. Multiple PET tracers are currently available to aid in the detection and management of prostate cancer across the clinical spectrum of the disease. Prospective, rigorously controlled, clinical imaging trials are needed to establish the optimal role of PET in prostate cancer.

  4. Testosterone replacement therapy and the risk of prostate cancer.

    PubMed

    Warburton, Daniel; Hobaugh, Christopher; Wang, Grace; Lin, Haocheng; Wang, Run

    2015-01-01

    Understanding the role of testosterone replacement therapy (TRT) in the development and progression of prostate cancer is an important concept in treating patients with symptoms of hypogonadism. This article revealed a small number of mostly retrospective, observational studies describing the use of TRT in the general population, in men with prostatic intraepithelial neoplasia (PIN), in men with a history of treated prostate cancer, and in men on active surveillance for prostate cancer. The current literature does not report a statistically significant increase in the development or progression of prostate cancer in men receiving testosterone replacement for symptomatic hypogonadism, and the prostate saturation theory provides a model explaining the basis for these results. The use of TRT in men with a history of prostate cancer is considered experimental, but future results from randomized controlled trials could lead to a change in our current treatment approach.

  5. Vaccine Treatment for Prostate Cancer

    MedlinePlus

    ... while you are hooked up to a special machine. The cells are then sent to a lab, where they are exposed to a protein from prostate cancer cells called prostatic acid phosphatase (PAP). The cells are then sent back to the doctor’s office or hospital, where they are given back to ... Information, ...

  6. The essential role of methylthioadenosine phosphorylase in prostate cancer

    PubMed Central

    Foster, Barbara A.; Karasik, Ellen; Gillard, Bryan; Morrison, Carl; Mohler, James; Phillips, James G.; Smiraglia, Dominic J.

    2016-01-01

    Prostatic epithelial cells secrete high levels of acetylated polyamines into the prostatic lumen. This distinctive characteristic places added strain on the connected pathways, which are forced to increase metabolite production to maintain pools. The methionine salvage pathway recycles the one-carbon unit lost to polyamine biosynthesis back to the methionine cycle, allowing for replenishment of SAM pools providing a mechanism to help mitigate metabolic stress associated with high flux through these pathways. The rate-limiting enzyme involved in this process is methylthioadenosine phosphorylase (MTAP), which, although commonly deleted in many cancers, is protected in prostate cancer. We report near universal retention of MTAP expression in a panel of human prostate cancer cell lines as well as patient samples. Upon metabolic perturbation, prostate cancer cell lines upregulate MTAP and this correlates with recovery of SAM levels. Furthermore, in a mouse model of prostate cancer we find that both normal prostate and diseased prostate maintain higher SAM levels than other tissues, even under increased metabolic stress. Finally, we show that knockdown of MTAP, both genetically and pharmacologically, blocks androgen sensitive prostate cancer growth in vivo. Our findings strongly suggest that the methionine salvage pathway is a major player in homeostatic regulation of metabolite pools in prostate cancer due to their high level of flux through the polyamine biosynthetic pathway. Therefore, this pathway, and specifically the MTAP enzyme, is an attractive therapeutic target for prostate cancer. PMID:26910893

  7. Magnetic nanoparticle hyperthermia enhances radiation therapy: A study in mouse models of human prostate cancer

    PubMed Central

    Attaluri, Anilchandra; Kandala, Sri Kamal; Wabler, Michele; Zhou, Haoming; Cornejo, Christine; Armour, Michael; Hedayati, Mohammad; Zhang, Yonggang; DeWeese, Theodore L.; Herman, Cila; Ivkov, Robert

    2015-01-01

    Purpose We aimed to characterise magnetic nanoparticle hyperthermia (mNPH) with radiation therapy (RT) for prostate cancer. Methods Human prostate cancer subcutaneous tumours, PC3 and LAPC-4, were grown in nude male mice. When tumours measured 150 mm3 magnetic iron oxide nanoparticles (MIONPs) were injected into tumours to a target dose of 5.5 mg Fe/cm3 tumour, and treated 24 h later by exposure to alternating magnetic field (AMF). Mice were randomly assigned to one of four cohorts to characterise (1) intratumour MIONP distribution, (2) effects of variable thermal dose mNPH (fixed AMF peak amplitude 24 kA/m at 160±5 kHz) with/without RT (5 Gy), (3) effects of RT (RT5: 5 Gy; RT8: 8 Gy), and (4) fixed thermal dose mNPH (43 °C for 20min) with/without RT (5 Gy). MIONP concentration and distribution were assessed following sacrifice and tissue harvest using inductively coupled plasma mass spectrometry (ICP-MS) and Prussian blue staining, respectively. Tumour growth was monitored and compared among treated groups. Results LAPC-4 tumours retained higher MIONP concentration and more uniform distribution than did PC3 tumours. AMF power modulation provided similar thermal dose for mNPH and combination therapy groups (CEM43: LAPC-4: 33.6 ± 3.4 versus 25.9 ± 0.8, and PC3: 27.19 ± 0.7 versus 27.50 ± 0.6), thereby overcoming limitations of MIONP distribution and yielding statistically significant tumour growth delay. Conclusion PC3 and LAPC-4 tumours represent two biological models that demonstrate different patterns of nanoparticle retention and distribution, offering a model to make comparisons of these effects for mNPH. Modulating power for mNPH offers potential to overcome limitations of MIONP distribution to enhance mNPH. PMID:25811736

  8. Prostate Cancer Aggressiveness Genes in Hereditary Prostate Cancer

    DTIC Science & Technology

    2006-03-01

    W81XWH-04- 1 -0314 TITLE: Prostate Cancer Aggressiveness Genes in Hereditary Prostate Cancer PRINCIPAL INVESTIGATOR: Kathleen A...burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching...ADDRESS. 1 . REPORT DATE (DD-MM-YYYY) March 2006 2. REPORT TYPE Annual 3. DATES COVERED (From - To) 1 Mar 05 – 28 Feb 06 5a. CONTRACT NUMBER

  9. Urinary Biomarkers for Prostate Cancer.

    PubMed

    Tosoian, Jeffrey J; Ross, Ashley E; Sokoll, Lori J; Partin, Alan W; Pavlovich, Christian P

    2016-02-01

    In light of the overdiagnosis and overtreatment associated with widespread prostate-specific antigen-based screening, controversy persists surrounding the detection and diagnosis of prostate cancer (PCa). Given its anatomic proximity to the prostate, urine has been proposed as a noninvasive substrate for prostatic biomarkers. With greater understanding of the molecular pathways of carcinogenesis and significant technological advances, the breadth of potential biomarkers is substantial. In this review, the authors aim to provide an evidence-based assessment of current and emerging urinary biomarkers used in the detection and prognostication of PCa and high-grade PCa, with particular attention on clinically relevant findings. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Is prostate cancer screening cost-effective? A microsimulation model of prostate-specific antigen-based screening for British Columbia, Canada.

    PubMed

    Pataky, Reka; Gulati, Roman; Etzioni, Ruth; Black, Peter; Chi, Kim N; Coldman, Andrew J; Pickles, Tom; Tyldesley, Scott; Peacock, Stuart

    2014-08-15

    Prostate-specific antigen (PSA) screening for prostate cancer may reduce mortality, but it incurs considerable risk of over diagnosis and potential harm to quality of life. Our objective was to evaluate the cost-effectiveness of PSA screening, with and without adjustment for quality of life, for the British Columbia (BC) population. We adapted an existing natural history model using BC incidence, treatment, cost and mortality patterns. The modeled mortality benefit of screening derives from a stage-shift mechanism, assuming mortality reduction consistent with the European Study of Randomized Screening for Prostate Cancer. The model projected outcomes for 40-year-old men under 14 combinations of screening ages and frequencies. Cost and utility estimates were explored with deterministic sensitivity analysis. The incremental cost-effectiveness of regular screening ranged from $36,300/LYG, for screening every four years from ages 55 to 69 years, to $588,300/LYG, for screening every two years from ages 40 to 74 years. The marginal benefits of increasing screening frequency to 2 years or starting screening at age 40 years were small and came at significant cost. After utility adjustment, all screening strategies resulted in a loss of quality-adjusted life years (QALYs); however, this result was very sensitive to utility estimates. Plausible outcomes under a range of screening strategies inform discussion of prostate cancer screening policy in BC and similar jurisdictions. Screening may be cost-effective, but the sensitivity of results to utility values suggests individual preferences for quality versus quantity of life should be a key consideration.

  11. Prostate Cancer Screening: MedlinePlus Health Topic

    MedlinePlus

    ... Prostate Cancer Screening (National Cancer Institute) Also in Spanish Latest News Prostate Cancer Symptoms Aren't Always ... Be Found Early? (American Cancer Society) Also in Spanish Risks of Prostate Cancer Screening (National Cancer Institute) ...

  12. Molecular subtyping of prostate cancer.

    PubMed

    Kaffenberger, Samuel D; Barbieri, Christopher E

    2016-05-01

    The recent publication of The Cancer Genome Atlas molecular taxonomy of primary prostate cancer highlights the increased understanding of the genomic basis of human prostate cancer, but also emphasizes the complexity and heterogeneity of prostate cancer. Seven molecular subclasses have been defined on the basis of early genomic alterations, which are largely mutually exclusive. We review the recent advances in the genomic understanding of human prostate cancer, with focus on molecular subclassification. Broadly, prostate cancer can be classified based upon whether specific genomic rearrangements, such as the Transmembrane Protease, Serine 2-ETS-related gene fusion occur or whether specific alterations such as Speckle-type POZ protein and forkhead box A1 mutations occur. The molecular drivers remain to be identified in a further quarter of human prostate cancers. Depending upon the molecular subclassification and the coincident genomic alterations, specific clinical insights can be gained from this information, including associations with pathologic factors, race, and prognosis, as well as the possibility for future precision therapies.

  13. Immunological Targeting of Tumor Initiating Prostate Cancer Cells

    DTIC Science & Technology

    2014-10-01

    clinically using well-accepted immuno-competent animal models. 2) Keywords: Prostate Cancer , Lymphocyte, Vaccine , Antibody 3) Overall Project Summary...generating a novel prostate cancer vaccine aimed at targeting the castration resistant epithelial cells left behind after initial androgen ablation. 6...of origin for prostate cancer . Nature 461:495-500. 2. Drake,C.G., E.J.Lipson, and J.R.Brahmer. 2014. Breathing new life into immunotherapy

  14. Prediction models for prostate cancer outcomes: what is the state of the art in 2017?

    PubMed

    Kearns, James T; Lin, Daniel W

    2017-09-01

    Prostate cancer (PCa) remains a significant public health burden, with multiple points for decision-making at all stages of the disease. Given the amount and variety of data that may influence disease management, prediction models have been published to assist clinicians and patients in making decisions about the best next course of action at many disease states. We sought to review the most important studies related to PCa prediction models since 2016 and evaluate their impact upon the evolving field of risk modeling in PCa. There has been a significant amount of work published in the past year concerning risk modeling in PCa at all stages of disease, ranging from screening to predicting survival with metastatic disease. The majority of recent publications focus upon the addition of a new biomarker to prediction models or upon validating previously published prediction models. In particular, MRI has been the topic of a number of more recent studies. Prediction modeling in PCa currently compares the area under the receiver operating curve between models with and without the biomarker of interest to predict the outcome of interest in multiple disease states, ranging from diagnosis to prediction of survival with metastatic disease. Future work should provide additional information regarding clinical impact and measures of prediction confidence.

  15. Photosensitizers in prostate cancer therapy

    PubMed Central

    Gheewala, Taher; Skwor, Troy; Munirathinam, Gnanasekar

    2017-01-01

    The search for new therapeutics for the treatment of prostate cancer is ongoing with a focus on the balance between the harms and benefits of treatment. New therapies are being constantly developed to offer treatments similar to radical therapies, with limited side effects. Photodynamic therapy (PDT) is a promising strategy in delivering focal treatment in primary as well as post radiotherapy prostate cancer. PDT involves activation of a photosensitizer (PS) by appropriate wavelength of light, generating transient levels of reactive oxygen species (ROS). Several photosensitizers have been developed with a focus on treating prostate cancer like mTHPC, motexafin lutetium, padoporfin and so on. This article will review newly developed photosensitizers under clinical trials for the treatment of prostate cancer, along with the potential advantages and disadvantages in delivering focal therapy. PMID:28430624

  16. Hormone Therapy for Prostate Cancer

    MedlinePlus

    ... 3-4):251-258. [PubMed Abstract] Lee RJ, Smith MR. Hormone Therapy for Prostate Cancer. In: Chabner ... 1, 2014. doi: 10.1056/NEJMoa1405095 Ryan CJ, Smith MR, Fizazi K, et al. Abiraterone acetate plus ...

  17. Tuberculous prostatitis: mimicking a cancer

    PubMed Central

    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. PMID:28292092

  18. Nebraska Prostate Cancer Research Program

    DTIC Science & Technology

    2014-07-01

    Effect of Metal Ion Chelators on Mannose 6-Phosphate/ Insulin -like Growth Factor II Receptor in DU145 Prostate Cancer Cells. UNMC Summer Undergraduate...Lynnette Lefall Date Published: Friday, August 6, 2010 Keidra Bryant – Abstract Effect of Metal Ion Chelators on Mannose 6-Phosphate/ Insulin ...chelators would inhibit this process in the insulin -like growth factor-responsive human prostate cancer cell line DU145. Cells were grown to 70-80

  19. Nebraska Prostate Cancer Research Program

    DTIC Science & Technology

    2012-05-01

    Expression in Prostate Cancer Cells Exposed to Heavy Metal Carcinogen. UNMC Summer Undergraduate Research Program, August 2010. • Keidra A. Bryant...Joseph R. Wheeler, Michelle A. Montgomery, and Richard G. MacDonald. (2010). Effect of Metal Ion Chelators on Mannose 6-Phosphate/Insulin-like... Effect of 4’-Bis-Thiosemicarbazide, a New Ribonucleotide Reductase Inhibitor, on Prostate Cancer Cell Proliferation. UNMC Summer Undergraduate Research

  20. Hyaluronan Biosynthesis in Prostate Cancer

    DTIC Science & Technology

    2006-01-01

    SUPPLEMENTARY NOTES 14. ABSTRACT: Despite advances in the diagnosis and treatment of prostate cancer in the last several years, metastasis represents the... metastasis to lymph nodes and bone. Metastasis to bone is especially noteworthy, not only because it reflects more advanced tumors, but also because of the...the growth and metastasis of androgen-independent tumors, it may be possible to better diagnose and treat prostate cancers by inhibiting growth of

  1. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1

    DTIC Science & Technology

    2012-12-01

    omega (ω)-3 or ω-6 polyunsaturated fatty acids ( PUFAs ) directly impact PCa...development. 15. SUBJECT TERMS Diet, polyunsaturated fatty acids ( PUFAs ), 15-lipoxygenase-1, cyclooxygenase, prostate cancer, Array, Genes. 16...competing with ω-6 fatty acids for 15-LO-1, and COX-2 activities. REPORTABLE OUTCOMES: None. CONCLUSION: Omega (ω)-3 fatty acids can

  2. Humanized Androgen Receptor Mice: A Genetic Model for Differential Response to Prostate Cancer Therapy

    DTIC Science & Technology

    2012-07-01

    with rapid testosterone uptake by cells and shorter duration of response to ketoconazole , a 17 lyase inhibitor used as secondary hormonal therapy...polymorphisms in SLCO1B3 gene and response to ketoconazole (K) in men with castration-resistant prostate cancer (CRPC). J Clin Oncol 2010;28:15s(suppl

  3. Notch signaling in prostate cancer: refining a therapeutic opportunity

    PubMed Central

    Su, Qingtai; Xin, Li

    2016-01-01

    Summary Notch is an evolutionarily conserved signaling pathway that plays a critical role in specifying cell fate and regulating tissue homeostasis and carcinogenesis. Studies using organ cultures and genetically engineered mouse models have demonstrated that Notch signaling regulates prostate development and homeostasis. However, the role of the Notch signaling pathway in prostate cancer remains inconclusive. Many published studies have documented consistent deregulation of major Notch signaling components in human prostate cancer cell lines, mouse models for prostate cancers, and human prostate cancer specimens at both the mRNA and the protein levels. However, functional studies in human cancer cells by modulation of Notch pathway elements suggest both tumor suppressive and oncogenic roles of Notch. These controversies may originate from our inadequate understanding of the regulation of Notch signaling under versatile genetic contexts, and reflect the multifaceted and pleiotropic roles of Notch in regulating different aspects of prostate cancer cell biology, such as proliferation, metastasis, and chemo-resistance. Future comprehensive studies using various mouse models for prostate cancer may help clarify the role of Notch signaling in prostate cancer and provide a solid basis for determining whether and how Notch should be employed as a therapeutic target for prostate cancer. PMID:26521657

  4. Obesity and Prostate Cancer: Weighing the Evidence

    PubMed Central

    Allott, Emma H.; Masko, Elizabeth M.; Freedland, Stephen J.

    2012-01-01

    Context Obesity and prostate cancer (PCa) affect substantial proportions of Western society. Mounting evidence, both epidemiologic and mechanistic, for an association between the two is of public health interest. An improved understanding of the role of this modifiable risk factor in PCa etiology is imperative to optimize screening, treatment, and prevention. Objective To consolidate and evaluate the evidence for an epidemiologic link between obesity and PCa, in addition to examining the proposed underlying molecular mechanisms. Evidence acquisition A PubMed search for relevant articles published between 1991 and July 2012 was performed by combining the following terms: obesity, BMI, body mass index and prostate cancer risk, prostate cancer incidence, prostate cancer mortality, radical prostatectomy, androgen-deprivation therapy, external-beam radiation, brachytherapy, prostate cancer and quality of life, prostate cancer and active surveillance, in addition to obesity, BMI, body mass index and prostate cancer and insulin, insulinlike growth factor, androgen, estradiol, leptin, adiponectin, and IL-6. Articles were selected based on content, date of publication, and relevancy, and their references were also searched for relevant articles. Evidence synthesis Increasing evidence suggests obesity is associated with elevated incidence of aggressive PCa, increased risk of biochemical failure following radical prostatectomy and external-beam radiotherapy, higher frequency of complications following androgen-deprivation therapy, and increased PCa-specific mortality, although perhaps a lower overall PCa incidence. These results may in part relate to difficulties in detecting and treating obese men. However, multiple molecular mechanisms could explain these associations as well. Weight loss slows PCa in animal models but has yet to be fully tested in human trials. Conclusions Obesity appears to be linked with aggressive PCa. We suggest clinical tips to better diagnose and

  5. Obesity and prostate cancer: weighing the evidence.

    PubMed

    Allott, Emma H; Masko, Elizabeth M; Freedland, Stephen J

    2013-05-01

    Obesity and prostate cancer (PCa) affect substantial proportions of Western society. Mounting evidence, both epidemiologic and mechanistic, for an association between the two is of public health interest. An improved understanding of the role of this modifiable risk factor in PCa etiology is imperative to optimize screening, treatment, and prevention. To consolidate and evaluate the evidence for an epidemiologic link between obesity and PCa, in addition to examining the proposed underlying molecular mechanisms. A PubMed search for relevant articles published between 1991 and July 2012 was performed by combining the following terms: obesity, BMI, body mass index and prostate cancer risk, prostate cancer incidence, prostate cancer mortality, radical prostatectomy, androgen-deprivation therapy, external-beam radiation, brachytherapy, prostate cancer and quality of life, prostate cancer and active surveillance, in addition to obesity, BMI, body mass index and prostate cancer and insulin, insulin-like growth factor, androgen, estradiol, leptin, adiponectin, and IL-6. Articles were selected based on content, date of publication, and relevancy, and their references were also searched for relevant articles. Increasing evidence suggests obesity is associated with elevated incidence of aggressive PCa, increased risk of biochemical failure following radical prostatectomy and external-beam radiotherapy, higher frequency of complications following androgen-deprivation therapy, and increased PCa-specific mortality, although perhaps a lower overall PCa incidence. These results may in part relate to difficulties in detecting and treating obese men. However, multiple molecular mechanisms could explain these associations as well. Weight loss slows PCa in animal models but has yet to be fully tested in human trials. Obesity appears to be linked with aggressive PCa. We suggest clinical tips to better diagnose and treat obese men with PCa. Whether reversing obesity slows PCa growth is

  6. Molecular Imaging of Prostate Cancer

    PubMed Central

    Fox, Josef J.; Schöder, Heiko; Larson, Steven M.

    2015-01-01

    Purpose of review Prostate cancer is a complex and biologically heterogeneous disease that is not adequately assessed with conventional imaging alone. Molecular imaging with positron emission tomography (PET) is poised to fill this unmet need through noninvasive probing of the multiple molecular and cellular processes that are active in prostate cancer patients. Recent findings Several PET tracers are active in early and late stage prostate cancer in humans. F18-FDG, C11/F18-choline and F18-sodium fluoride (NaF) have been studied most extensively. There is a growing body of literature supporting to the utility of choline in early stage prostate cancer. FDG and NaF are more valuable in advanced disease, especially for assessing bone metastases, the prevalent form of metastases in this patient population. F18-Fluoro-dihydrotestosterone is active in castrate disease and is emerging as a valuable pharmacodynamic marker in the development of novel AR-targeted therapies. Anti-PSMA PET tracers are in the early stages of clinical development. Summary Multiple PET tracers are currently available to aid in the detection and management of prostate cancer across the clinical spectrum of the disease. Prospective, rigorously controlled, clinical imaging trials are needed to establish the optimal role of PET in prostate cancer. PMID:22617062

  7. Immunotherapy in metastatic prostate cancer

    PubMed Central

    Slovin, Susan F.

    2016-01-01

    Introduction: Prostate cancer remains a challenge as a target for immunological approaches. The approval of the first cell-based immune therapy, Sipuleucel-T for prostate cancer introduced prostate cancer as a solid tumor with the potential to be influenced by the immune system. Methods: We reviewed articles on immunological management of prostate cancer and challenges that lie ahead for such strategies. Results: Treatments have focused on the identification of novel cell surface antigens thought to be unique to prostate cancer. These include vaccines against carbohydrate and blood group antigens, xenogeneic and naked DNA vaccines, and pox viruses used as prime-boost or checkpoint inhibitors. No single vaccine construct to date has resulted in a dramatic antitumor effect. The checkpoint inhibitor, anti-CTLA-4 has resulted in several long-term remissions, but phase III trials have not demonstrated an antitumor effect or survival benefit. Conclusions: Multiple clinical trials suggest that prostate cancer may not be optimally treated by single agent immune therapies and that combination with biologic agents, chemotherapies, or radiation may offer some enhancement of benefit. PMID:27843208

  8. Prostate-specific antigen levels as a predictor of lethal prostate cancer.

    PubMed

    Fall, Katja; Garmo, Hans; Andrén, Ove; Bill-Axelson, Anna; Adolfsson, Jan; Adami, Hans-Olov; Johansson, Jan-Erik; Holmberg, Lars

    2007-04-04

    Rates of long-term survival among patients with untreated localized prostate cancer are high. To avoid unnecessary treatment, tools are needed to identify the small proportion of patients who are destined to develop lethal prostate cancer. To evaluate the accuracy of early changes in prostate-specific antigen (PSA) levels as predictors of prostate cancer outcome, we assessed serial measurements of PSA level among 267 men with localized prostate cancer in a Scandinavian cohort of men who were diagnosed between 1989 and 1999 and who were managed by watchful waiting. We then 1) fitted individual regression lines to the PSA values assessed for each patient during the first 2 years of follow-up by using three different models, 2) evaluated early PSA curve characteristics as determinants of the cumulative incidence of lethal prostate cancer and calculated hazard ratios for baseline PSA value and rate of change in PSA level to prostate cancer outcome, and 3) plotted time-dependent receiver operating characteristic (ROC) curves. All P values are two-sided. During complete follow-up for a mean of 8.5 years, 34 patients (13%) died from prostate cancer, and 18 (7%) developed metastases but were still alive at end of follow-up. In a log-linear model, both PSA value at baseline (P = .05) and the rate of PSA change (P<.001) were associated with the development of lethal prostate cancer. In the ROC analysis, however, the accuracy of classifying the disease as either indolent or destined to progress was low, regardless of the cut point chosen for initial PSA level or rate of change in PSA level. Although baseline PSA value and rate of PSA change are prognostic factors for lethal prostate cancer, they are poor predictors of lethal prostate cancer among patients with localized prostate cancer who are managed by watchful waiting.

  9. Hierarchical and Multiscale Modeling for Elucidating the Androgren Receptor Signaling Pathway in Prostate Cancer

    DTIC Science & Technology

    2009-10-01

    cancers as a guide to targeted therapies. Nature 439:353-57. [34] Prasad, T. S . K., Goel, R., Kandasamy , K., Keerthikumar, S ., et al. (2009) Human...The views, opinions and/or findings contained in this report are those of the author( s ) and should not be construed as an official...Pathway in Prostate Cancer 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER Justin Guinney 6. AUTHOR( S ) 5d. PROJECT NUMBER 5e

  10. 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.

  11. The therapeutic efficacy of I131-PSCA-mAb in orthotopic mouse models of prostate cancer

    PubMed Central

    2013-01-01

    Background Prostate stem cell antigen (PSCA) is upregulated in prostate cancer tissues. Here we aimed to study the therapeutic efficacy of a monoclonal antibody of PSCA-labeled I131 (I131-PSCA-mAb) in orthotopic mouse models of prostate cancer. Methods The proliferation, apoptosis and invasion abilities of PC-3 and LNCaP cells treated with I131-PSCA-mAb were measured by methyl thiazolyl tetrazolium assay, flow cytometry and transwell culture, respectively. The human prostate cancer models were established by orthotopic implantation of PC-3 and LNCaP cells in nude mice. I131-PSCA-mAb distribution and tumor cell apoptosis in the tumor-bearing nude mice were measured. Results The inhibitory and apoptosis rates of PC-3 and LNCaP cells treated with I131-PSCA-mAb reached a maximum of 84%, 80% and 50%, 46%, respectively, which were obviously higher than in the cells treated with I131-IgG or PSCA-mAb. The invaded number of PC-3 and LNCaP cells treated with I131-PSCA-mAbe was significantly reduced (P < 0.01) compared with the control group. The ratios of I131-PSCA-mAb in tumor to intramuscular I131-PSCA-mAb (T/NT) in tumor-bearing nude mice were increased with time and reached the highest level after 8 h. T/NT stayed above 3.0 after 12 h, and the tumor could still be developed after 24 h. The number of apoptotic cells in tumor tissue of nude mice treated with I131-PSCA-mAb was larger than that in the control group. Conclusion I131-PSCA-mAb has the potential to become a new targeted therapy drug for the treatment of prostate cancer. PMID:24330823

  12. A semi-automated 2D/3D marker-based registration algorithm modelling prostate shrinkage during radiotherapy for prostate cancer.

    PubMed

    Budiharto, Tom; Slagmolen, Pieter; Hermans, Jeroen; Maes, Frederik; Verstraete, Jan; Heuvel, Frank Van den; Depuydt, Tom; Oyen, Raymond; Haustermans, Karin

    2009-03-01

    Currently, most available patient alignment tools based on implanted markers use manual marker matching and rigid registration transformations to measure the needed translational shifts. To quantify the particular effect of prostate gland shrinkage, implanted gold markers were tracked during a course of radiotherapy including an isotropic scaling factor to model prostate shrinkage. Eight patients with prostate cancer had gold markers implanted transrectally and seven were treated with (neo) adjuvant androgen deprivation therapy. After patient alignment to skin tattoos, orthogonal electronic portal images (EPIs) were taken. A semi-automated 2D/3D marker-based registration was performed to calculate the necessary couch shifts. The registration consists of a rigid transformation combined with an isotropic scaling to model prostate shrinkage. The inclusion of an isotropic shrinkage model in the registration algorithm cancelled the corresponding increase in registration error. The mean scaling factor was 0.89+/-0.09. For all but two patients, a decrease of the isotropic scaling factor during treatment was observed. However, there was almost no difference in the translation offset between the manual matching of the EPIs to the digitally reconstructed radiographs and the semi-automated 2D/3D registration. A decrease in the intermarker distance was found correlating with prostate shrinkage rather than with random marker migration. Inclusion of shrinkage in the registration process reduces registration errors during a course of radiotherapy. Nevertheless, this did not lead to a clinically significant change in the proposed table translations when compared to translations obtained with manual marker matching without a scaling correction.

  13. PROSTATE REGULATION: MODELING ENDOGENOUS ...

    EPA Pesticide Factsheets

    Prostate function is an important indicator of androgen status in toxicological studies making predictive modeling of the relevant pharmacokinetics and pharmacodynamics desirable. Prostate function is an important indicator of androgen status in toxicological studies making predictive modeling of the relevant pharmacokinetics and pharmacodynamics desirable.

  14. Lycopene: Redress for Prostate Cancer

    PubMed Central

    Pisipati, Sai Venkata Vedavyas; Pathapati, Harshavardhan; Bhukya, Ganesh; Nuthakki, Suresh; Chandu, Baburao; Nama, SreeKanth; Adeps, RajDev

    2012-01-01

    Lycopene, a carotenoid is what that gives red colour to some fruits like pomegranate, tomato, papaya etc... People with a sound diet of lycopene may have a less risk of cancers especially prostate cancer which is most impedent for the males of age 40-50 years. So, in countries of north America and Europe food contains much of the lycopene supplements. In accordance with the American journal of epidemiology 2002 studies implies that men with crushed serum lycopene levels are more divulged to prostate cancer and those with sound diet of lycopene have a less risk of prostate cancer. In a care study conveyed by The British journal of urology, men with prostate cancer are subjected to surgery and the tumour is detonated. Amongst the men half a set were supplemented with lycopene supplements and half were not. Those subjected with lycopene supplements have less bone pains and live longer than those not supplemented. This paints a picture about importance of lycopene in treatment of prostate cancer. This article evokes the importance of lycopene and its way of destroying the cancer. Lycopene reduces the risk of cancer by diverging its effect on the plasma Insulin like growth factor, on Connexins , and the most acceptable one, by quench of free radicals. PMID:24826034

  15. Lycopene: redress for prostate cancer.

    PubMed

    Pisipati, Sai Venkata Vedavyas; Pathapati, Harshavardhan; Bhukya, Ganesh; Nuthakki, Suresh; Chandu, Baburao; Nama, SreeKanth; Adeps, RajDev

    2012-03-01

    Lycopene, a carotenoid is what that gives red colour to some fruits like pomegranate, tomato, papaya etc... People with a sound diet of lycopene may have a less risk of cancers especially prostate cancer which is most impedent for the males of age 40-50 years. So, in countries of north America and Europe food contains much of the lycopene supplements. In accordance with the American journal of epidemiology 2002 studies implies that men with crushed serum lycopene levels are more divulged to prostate cancer and those with sound diet of lycopene have a less risk of prostate cancer. In a care study conveyed by The British journal of urology, men with prostate cancer are subjected to surgery and the tumour is detonated. Amongst the men half a set were supplemented with lycopene supplements and half were not. Those subjected with lycopene supplements have less bone pains and live longer than those not supplemented. This paints a picture about importance of lycopene in treatment of prostate cancer. This article evokes the importance of lycopene and its way of destroying the cancer. Lycopene reduces the risk of cancer by diverging its effect on the plasma Insulin like growth factor, on Connexins , and the most acceptable one, by quench of free radicals.

  16. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

    DTIC Science & Technology

    2016-12-01

    lipids in test controls. Key Metabolomics Research Accomplishments 1) Developed unbiased mass spectrometry methods to profile 500 lipids . 2) Completed...Award Number: W81XWH-12-1-0168 TITLE: Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer PRINCIPAL INVESTIGATOR: Jackilen...Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0168 5c. PROGRAM ELEMENT NUMBER

  17. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

    DTIC Science & Technology

    2016-11-01

    test controls. Key Metabolomics Research Accomplishments 1) Developed unbiased mass spectrometry methods to profile 500 lipids . 2) Completed...Award Number: W81XWH-12-1-0169 PC110361P1 TITLE: Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer PRINCIPAL INVESTIGATOR...SUBTITLE Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0169 5c. PROGRAM

  18. Novel Lignan and Stilbenoid Mixture Shows Anticarcinogenic Efficacy in Preclinical PC-3M-luc2 Prostate Cancer Model

    PubMed Central

    Laajala, Teemu D.; Smeds, Annika; Eckerman, Christer; Holmbom, Bjarne; Saarinen, Niina M.; Aittokallio, Tero; Mäkelä, Sari I.

    2014-01-01

    Prostate cancer is the most common cancer of men in the Western world, and novel approaches for prostate cancer risk reduction are needed. Plant-derived phenolic compounds attenuate prostate cancer growth in preclinical models by several mechanisms, which is in line with epidemiological findings suggesting that consumption of plant-based diets is associated with low risk of prostate cancer. The objective of this study was to assess the effects of a novel lignan-stilbenoid mixture in PC-3M-luc2 human prostate cancer cells in vitro and in orthotopic xenografts. Lignan and stilbenoid –rich extract was obtained from Scots pine (Pinus sylvestris) knots. Pine knot extract as well as stilbenoids (methyl pinosylvin and pinosylvin), and lignans (matairesinol and nortrachelogenin) present in pine knot extract showed antiproliferative and proapoptotic efficacy at ≥40 μM concentration in vitro. Furthermore, pine knot extract derived stilbenoids enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induced apoptosis already at ≥10 μM concentrations. In orthotopic PC-3M-luc2 xenograft bearing immunocompromized mice, three-week peroral exposure to pine knot extract (52 mg of lignans and stilbenoids per kg of body weight) was well tolerated and showed anti-tumorigenic efficacy, demonstrated by multivariate analysis combining essential markers of tumor growth (i.e. tumor volume, vascularization, and cell proliferation). Methyl pinosylvin, pinosylvin, matairesinol, nortrachelogenin, as well as resveratrol, a metabolite of pinosylvin, were detected in serum at total concentration of 7−73 μM, confirming the bioavailability of pine knot extract derived lignans and stilbenoids. In summary, our data indicates that pine knot extract is a novel and cost-effective source of resveratrol, methyl pinosylvin and other bioactive lignans and stilbenoids. Pine knot extract shows anticarcinogenic efficacy in preclinical prostate cancer model, and our in vitro data

  19. Prostate cancer: endogenous chemical castration.

    PubMed

    McCoy, Olugbemisola Oredein; Prasad, Michaella M; Singer, Natalie

    2016-04-28

    We report treatment of intermediate risk prostate cancer in a patient with a brief period of androgen deprivation secondary to a pituitary adenoma. This was a patient with intermediate risk prostate cancer diagnosed in the setting of an elevated prostate-specific antigen (PSA). The patient subsequently demonstrated a decline in PSA along with symptoms of hypogonadism and visual disturbance, and was consequently found to have a pituitary tumour. Trans-sphenoidal resection of the sellar mass was performed with normalisation of hormone profiles. The patient subsequently completed a course of radiation therapy for prostate cancer with PSA nadir to undetectable levels without evidence of biochemical recurrence at 7 months follow-up. 2016 BMJ Publishing Group Ltd.

  20. Targeting tissue factor on tumor vascular endothelial cells and tumor cells for immunotherapy in mouse models of prostatic cancer.

    PubMed

    Hu, Z; Garen, A

    2001-10-09

    The efficacy and safety of an immunoconjugate (icon) molecule, composed of a mutated mouse factor VII (mfVII) targeting domain and the Fc effector domain of an IgG1 Ig (mfVII/Fc icon), was tested with a severe combined immunodeficient (SCID) mouse model of human prostatic cancer and an immunocompetent mouse model of mouse prostatic cancer. The SCID mice were first injected s.c. with a human prostatic tumor line, forming a skin tumor that produces a high blood titer of prostate-specific antigen and metastasizes to bone. The icon was encoded in a replication-incompetent adenoviral vector that was injected directly into the skin tumor. The tumor cells infected by the vector synthesize and secrete the icon into the blood, and the blood-borne icon binds with high affinity and specificity to mouse tissue factor expressed on endothelial cells lining the lumen of the tumor vasculature and to human tissue factor expressed on the tumor cells. The Fc domain of the icon activates a cytolytic immune attack against cells that bind the icon. The immunotherapy tests in SCID mice demonstrated that intratumoral injections of the adenoviral vector encoding the mfVII/human Fc icon resulted in long-term regression of the injected human prostatic tumor and also of a distant uninjected tumor, without associated toxicity to the mice. Comparable results were obtained with a SCID mouse model of human melanoma. At the end of the experiments the mice appeared to be free of viable tumor cells. This protocol also could be efficacious for treating cancer patients who have vascularized tumors.

  1. Sirolimus, Docetaxel, and Carboplatin in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

    ClinicalTrials.gov

    2016-11-10

    Castration Levels of Testosterone; Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Prostate Carcinoma Metastatic in the Bone; PSA Progression; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

  2. Impact of Prostate Cancer Diagnosis on Non-Cancer Hospitalizations among Elderly Medicare Beneficiaries with Incident Prostate Cancer

    PubMed Central

    Raval, Amit D.; Madhavan, Suresh; Mattes, Malcolm D.; Salkini, Mohamad; Sambamoorthi, Usha

    2016-01-01

    OBJECTIVES To analyze the impact of cancer diagnosis on non-cancer hospitalizations (NCHs) by comparing these hospitalizations between the pre- and post-cancer period in a cohort of fee-for-service Medicare beneficiaries with incident prostate cancer. METHODS A population-based retrospective cohort study was conducted using the Surveillance, Epidemiology and End-Results (SEER) -Medicare linked database for the years 2000 to 2010. The study cohort consisted of 57,489 elderly men (≥ 67 years) with incident prostate cancer. NCHs were identified in six time periods (t1–t6) before and after the incidence of prostate cancer. Each time period consisted of 120 days. For each time period, NCHs were defined as inpatient admissions with primary diagnosis codes not related to prostate cancer, prostate cancer-related procedures or bowel, sexual and urinary dysfunction. Bivariate and multivariate comparisons on rates of NCHs between the pre- and post-cancer period accounted for the repeated measures design. RESULTS The rate of NCHs during the post-cancer period (5.1%) was higher as compared to the pre-cancer period (3.2%). In both unadjusted and adjusted models, elderly men were 37% (Odds Ratio, OR: 1.37, 95% Confidence Interval, CI: 1.32, 1.41) and 38% (Adjusted OR: 1.38, 95% CI: 1.33, 1.46) more likely to have any NCH during the post-cancer period as compared to the pre-cancer period. CONCLUSIONS Elderly men with prostate cancer had a significant increase in the risk of NCHs after the diagnosis of prostate cancer. The study highlights the need to design interventions for reducing the excess NCHs after diagnosis of prostate cancer among elderly men. PMID:26850489

  3. Hyaluronan Tumor Cell Interactions in Prostate Cancer Growth and Survival

    DTIC Science & Technology

    2009-12-01

    Score (Figure 2B). Elevated levels of both HA (Figure 3A) and Hyal- 1(Figure 3B) were also observed in both BPH and prostate cancer, with a...elevated in BPH , and most strongly elevated in prostate carcinomas (Figure 2B). The intensity of RHAMM staining increased as a function of Gleason...by co-precipitation. Studies are currently underway to test this model in the prostate cancer model. 2. RHAMM expression should enhance the level of

  4. Prostate cancer risk alleles are associated with prostate cancer volume and prostate size.

    PubMed

    Reinhardt, Daniel; Helfand, Brian T; Cooper, Phillip R; Roehl, Kimberly A; Catalona, William J; Loeb, Stacy

    2014-06-01

    Genome-wide association studies have identified an increasing number of single nucleotide polymorphisms associated with prostate cancer risk. Some of these genetic variants are also associated with serum prostate specific antigen levels and lower urinary tract symptoms, raising the question of whether they are truly prostate cancer biomarkers or simply lead to detection bias. Therefore, we determined whether single nucleotide polymorphisms associated with prostate cancer risk are more strongly associated with tumor or prostate volume. The genotypes of 38 validated prostate cancer risk single nucleotide polymorphisms were determined in 1,321 white men who underwent radical prostatectomy. Univariate and multivariate analyses were performed to compare the relationship of single nucleotide polymorphism frequency with total prostate and tumor volumes. On multivariate analysis 2 single nucleotide polymorphisms on chromosome 8q24, rs16901979 (A) and rs6983267 (G), were significantly associated with increased tumor volume (p=0.01 and 0.02, respectively). In contrast, rs17632542 (T) near the PSA gene on 19q13 was associated with significantly lower tumor volume and rs10788160 (A) on 10q26 was associated with significantly larger prostate volume (p=0.02 and 0.01, respectively). Analysis of 38 single nucleotide polymorphisms associated with prostate cancer risk revealed a significant association between several on chromosome 8q24 and increased tumor volume but not prostate volume. This suggests that they are bona fide markers of prostate cancer susceptibility and possibly more aggressive disease. Other prostate cancer risk alleles are associated with prostate specific antigen and increased prostate or decreased tumor volume, suggesting detection bias due to their phenotypic influence. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  5. The Danish Prostate Cancer Database

    PubMed Central

    Nguyen-Nielsen, Mary; Høyer, Søren; Friis, Søren; Hansen, Steinbjørn; Brasso, Klaus; Jakobsen, Erik Breth; Moe, Mette; Larsson, Heidi; Søgaard, Mette; Nakano, Anne; Borre, Michael

    2016-01-01

    Aim of database The Danish Prostate Cancer Database (DAPROCAdata) is a nationwide clinical cancer database that has prospectively collected data on patients with incident prostate cancer in Denmark since February 2010. The overall aim of the DAPROCAdata is to improve the quality of prostate cancer care in Denmark by systematically collecting key clinical variables for the purposes of health care monitoring, quality improvement, and research. Study population All Danish patients with histologically verified prostate cancer are included in the DAPROCAdata. Main variables The DAPROCAdata registers clinical data and selected characteristics for patients with prostate cancer at diagnosis. Data are collected from the linkage of nationwide health registries and supplemented with online registration of key clinical variables by treating physicians at urological and oncological departments. Main variables include Gleason scores, cancer staging, prostate-specific antigen values, and therapeutic measures (active surveillance, surgery, radiotherapy, endocrine therapy, and chemotherapy). Descriptive data In total, 22,332 patients with prostate cancer were registered in DAPROCAdata as of April 2015. A key feature of DAPROCAdata is the routine collection of patient-reported outcome measures (PROM), including data on quality-of-life (pain levels, physical activity, sexual function, depression, urine and fecal incontinence) and lifestyle factors (smoking, alcohol consumption, and body mass index). PROM data are derived from questionnaires distributed at diagnosis and at 1-year and 3-year follow-up. Hitherto, the PROM data have been limited by low completeness (26% among newly diagnosed patients in 2014). Conclusion DAPROCAdata is a comprehensive, yet still young clinical database. Efforts to improve data collection, data validity, and completeness are ongoing and of high priority. PMID:27843346

  6. Molecular therapeutics in prostate cancer.

    PubMed

    Nicholson, B; Theodorescu, D

    2003-01-01

    The purpose of this review is to provide information on the molecular basis of prostate cancer biology and to identify some of the targets for therapy, and highlight some potential strategies for molecular treatment. Here we give a synopsis of what we have learned regarding molecular biology of cancer in general and the directions research might take in the future in order to impact prostate cancer specifically. This work is certainly not encyclopedic in nature and we apologize in advance to colleagues whose work we were no able to include. Hope lies in learning to utilize some of these molecular workings for better prevention, diagnosis, and treatment of the most common solid organ cancer in men. Prostate cancer is a formidable disease and at current rates of diagnosis will affect one-in-six men living in the United States (Greenlee et al., 2000) Many of these men are diagnosed at an early stage of the disease and can be effectively treated by surgery or radiation. However, a significant fraction of men are diagnosed with later stage disease or progress despite early curative therapeutic attempts. Unfortunately, many of these men succumb to prostate cancer, as management options are limited and not always successful. Through an understanding of the molecular processes that occur in the development and progression of prostate cancer, novel therapies will arise that will provide longer survival, better quality of life, and a chance for cure in men afflicted with this disease.

  7. The establishment and evaluation of a new model for the prediction of prostate cancer

    PubMed Central

    Wang, Qi; Li, Yan-Feng; Jiang, Jun; Zhang, Yong; Liu, Xu-Dong; Li, Ke

    2017-01-01

    Abstract To develop a new prostate cancer predictor (PCP) model using the combination of total prostate-specific antigen (tPSA), free PSA (fPSA), and complexed PSA (cPSA). The diagnoses of all the included patients were confirmed pathologically in Daping Hospital between December 1, 2011 and December 1, 2014. There were 54 PCa cases and 579 benign prostatic hyperplasia (BPH) cases with tPSA levels of 2 to 10 ng/mL, and 48 PCa cases and 147 BPH cases with tPSA levels of 10 to 20 ng/mL. Logistic regression and receiver operating characteristic curve (ROC) analyses were employed to compare the value of PCP (PCP = tPSA / fPSA × √cPSA) with tPSA, fPSA, the ratio of fPSA to tPSA (%fPSA), and cPSA for the differential diagnosis of PCa and BPH. Meanwhile, bootstrapping analysis was used to calculate the distribution and confidence intervals (CIs) for the area under the curve (AUC), and Hosmer–Lemeshow tests were used to calculate P values. When tPSA levels were 2 to 10 ng/mL, the AUC of PCP (0.680) was significantly higher than that of tPSA (0.588), fPSA (0.571), %fPSA (0.675), and cPSA (0.613). When the sensitivity for the diagnosis of PCa was 90.7%, the specificity of PCP (22.8%) was higher than that of tPSA (11.1%), fPSA (11.2%), %fPSA (17.4%), and cPSA (15.5%). When tPSA levels were 10 to 20 ng/mL, the AUC of PCP (0.686) was significantly higher than that of tPSA (0.603), fPSA (0.643), %fPSA (0.679), and cPSA (0.647). When the sensitivity for the diagnosis of PCa was 91.7%, the specificity of PCP (29.3%) was higher than that of tPSA (10.9%), fPSA (10.2%), %fPSA (23.1%), and cPSA (18.4%). PCP is a novel model for the prediction of PCa; it has more predictive value than tPSA, fPSA, %fPSA, and cPSA when tPSA levels are 2 to 20 ng/mL. PMID:28296726

  8. [The epidemiology of prostate cancer].

    PubMed

    Rébillard, Xavier; Tretarre, Brigitte; Villers, Arnauld

    2003-12-31

    Prostate cancer is a public health problem. Currently, it is the most frequent cause of cancer, and the second most common cause of cancer mortality, in men in most developed countries. Its incidence in France in 2000 is close to 40 000 new cases, a consistent increase of 7,9% per year. One man in 8 in France will be diagnosed with prostate cancer in the course of his life. More than half of these cancers are diagnosed before 75 years, most often at a localized stage accessible to a curative treatment. The increasing practice of PSA testing and systematic prostatic biopsies are responsible for this rise in incidence. The mortality is stable at around 10 000 per year in France. Hereditary risk factors permit a definition of a target population for screening. Environmental factors are little known, but a diet rich in fat seems to be associated with a more elevated risk.

  9. Prostate Cancer: Symptoms, Tests, and Treatment

    MedlinePlus

    ... Products For Consumers Home For Consumers Consumer Updates Prostate Cancer: Symptoms, Tests, and Treatment Share Tweet Linkedin Pin ... Linkedin Pin it Email Print Risk factors for prostate cancer include family history, age and race; but new ...

  10. Metabolic Risk Factors in Prostate Cancer

    PubMed Central

    Chu, David I.; Freedland, Stephen J.

    2010-01-01

    The biology of prostate cancer is influenced by the metabolic profile of each individual. We examine the evidence available interlinking prostate cancer with obesity, diabetes, and other metabolic syndrome components. PMID:21523712

  11. Prostate cancer gene 3 urine assay for prostate cancer in Japanese men undergoing prostate biopsy.

    PubMed

    Ochiai, Atsushi; Okihara, Koji; Kamoi, Kazumi; Iwata, Tsuyoshi; Kawauchi, Akihiro; Miki, Tsuneharu; Fors, Zephyr

    2011-03-01

    To examine the clinical utility of the prostate cancer gene 3 (PCA3) urine test in predicting prostate cancer in Japanese men undergoing prostate biopsy. The study group included 105 men who underwent extended prostate biopsy based on an elevated serum prostate-specific antigen (PSA). In all cases, the patients' race was Asian. Urine specimens were collected after digital rectal examination, and PCA3 score (PCA3/PSA mRNA) was determined in the urine using the APTIMA PCA3 assay. PCA3 score was investigated for a correlation with serum PSA, prostate volume (PV), PSA density and biopsy outcome. All urine samples collected were successfully analyzed (i.e. the informative specimen rate was 100%). Biopsy showed prostate cancer in 38 men (36%). The PCA3 score was not associated with serum PSA nor PV. The median PCA3 score in prostate cancer was significantly higher than that in negative biopsy (59.5 vs 14.2 P<0.0001). The probability of prostate cancer was 69% at a PCA3 score of more than 50 and 5% at a PCA3 score of less than 20. On multivariable logistic regression, PSA density (P<0.05) and PCA3 score (P<0.0001) were the independent predictors for prostate cancer. There was no significant difference in AUC between PCA3 score and PSA density. The combination of PCA3 score and PSA density increased the AUC from 0.72 for PSA alone to 0.88. The specificity of the PCA3 urine assay for prostate cancer was excellent in Japanese men undergoing biopsy. PCA3 score could improve the prediction for prostate cancer and help to better select men who might benefit from prostate biopsy. © 2011 The Japanese Urological Association.

  12. Height and Prostate Cancer Risk

    PubMed Central

    Zuccolo, Luisa; Harris, Ross; Gunnell, David; Oliver, Steven; Lane, Jane Athene; Davis, Michael; Donovan, Jenny; Neal, David; Hamdy, Freddie; Beynon, Rebecca; Savovic, Jelena; Martin, Richard Michael

    2008-01-01

    Background Height, a marker of childhood environmental exposures, is positively associated with prostate cancer risk, perhaps through the insulin-like growth factor system. We investigated the relationship of prostate cancer with height and its components (leg and trunk length) in a nested case-control study and with height in a dose-response meta-analysis. Methods We nested a case-control study within a population-based randomized controlled trial evaluating treatments for localized prostate cancer in British men ages 50 to 69 years, including 1,357 cases detected through prostate-specific antigen testing and 7,990 controls (matched on age, general practice, assessment date). Nine bibliographic databases were searched systematically for studies on the height-prostate cancer association that were pooled in a meta-analysis. Results Based on the nested case-control, the odds ratio (OR) of prostate-specific antigen-detected prostate cancer per 10 cm increase in height was 1.06 [95% confidence interval (95% CI): 0.97-1.16; ptrend = 0.2]. There was stronger evidence of an association of height with high-grade prostate cancer (OR: 1.23; 95% CI: 1.06-1.43), mainly due to the leg component, but not with low-grade disease (OR: 0.99; 95% CI: 0.90-1.10). In general, associations with leg or trunk length were similar. A meta-analysis of 58 studies found evidence that height is positively associated with prostate cancer (random-effects OR per 10 cm: 1.06; 95% CI: 1.03-1.09), with a stronger effect for prospective studies of more advanced/aggressive cancers (random-effects OR: 1.12; 95% CI: 1.05-1.19). Conclusion These data indicate a limited role for childhood environmental exposures—as indexed by adult height—on prostate cancer incidence, while suggesting a greater role for progression, through mechanisms requiring further investigation. PMID:18768501

  13. Chronic Chlorpyrifos Exposure Does Not Promote Prostate Cancer in Prostate Specific PTEN Mutant Mice

    PubMed Central

    Svensson, Robert U.; Bannick, Nadine L.; Marin, Maximo J.; Robertson, Larry W.; Lynch, Charles F.; Henry, Michael D.

    2014-01-01

    Environmental factors are likely to interact with genetic determinants to influence prostate cancer progression. The Agricultural Health Study has identified an association between exposure to organophosphorous pesticides including chlorpyrifos, and increased prostate cancer risk in pesticide applicators with a first-degree family history of this disease. Exploration of this potential gene-environment interaction would benefit from the development of a suitable animal model. Utilizing a previously described mouse model that is genetically predisposed to prostate cancer through a prostate-specific heterozygous PTEN deletion, termed C57/Luc/Ptenp+/−, we used bioluminescence imaging and histopathological analyses to test whether chronic exposure to chlorpyrifos in a grain-based diet for 32 weeks was able to promote prostate cancer development. Chronic exposure to chlorpyrifos in the diet did not promote prostate cancer development in C57/Luc/Ptenp+/− mice despite achieving sufficient levels to inhibit acetylcholinesterase activity in plasma. We found no significant differences in numbers of murine prostatic intraepithelial neoplasia lesions or disease progression in chlorpyrifos versus control treated animals up to 32 weeks. The mechanistic basis of pesticide-induced prostate cancer may be complex and may involve other genetic variants, multiple genes, or nongenetic factors that might alter prostate cancer risk during pesticide exposure in agricultural workers. PMID:23758150

  14. Prostate cancer in dogs: comparative and clinical aspects.

    PubMed

    Leroy, Bruce E; Northrup, Nicole

    2009-05-01

    The canine prostate gland shares many morphological and functional similarities with the human prostate and dogs are the only other large mammals that commonly develop spontaneous prostate cancer. However, the incidence of prostate cancer is much lower in dogs and the precise cell of origin is not known. Dogs with prostate cancer usually present with advanced disease that does not respond to androgen deprivation therapy. Similar to humans, affected dogs often develop osteoblastic bone metastases in the pelvis and/or lumbar spine with associated pain and neurological deficits. Other clinical signs include weight loss, lethargy, and abnormal urination and/or defecation. Surgery, chemotherapy, and radiation have been used to treat dogs with prostate cancer, but success has been limited by the location and aggressive nature of the disease. It is evident that better methods of early detection and more effective therapies are needed for prostate cancer in dogs and advanced prostate carcinoma in men. Dogs with naturally-occurring prostate cancer are relevant models for the disease in humans and pre-clinical studies of new diagnostics and therapies in dogs may benefit both humans and dogs with prostate cancer.

  15. Epigenetics of prostate cancer.

    PubMed

    McKee, Tawnya C; Tricoli, James V

    2015-01-01

    The introduction of novel technologies that can be applied to the investigation of the molecular underpinnings of human cancer has allowed for new insights into the mechanisms associated with tumor development and progression. They have also advanced the diagnosis, prognosis and treatment of cancer. These technologies include microarray and other analysis methods for the generation of large-scale gene expression data on both mRNA and miRNA, next-generation DNA sequencing technologies utilizing a number of platforms to perform whole genome, whole exome, or targeted DNA sequencing to determine somatic mutational differences and gene rearrangements, and a variety of proteomic analysis platforms including liquid chromatography/mass spectrometry (LC/MS) analysis to survey alterations in protein profiles in tumors. One other important advancement has been our current ability to survey the methylome of human tumors in a comprehensive fashion through the use of sequence-based and array-based methylation analysis (Bock et al., Nat Biotechnol 28:1106-1114, 2010; Harris et al., Nat Biotechnol 28:1097-1105, 2010). The focus of this chapter is to present and discuss the evidence for key genes involved in prostate tumor development, progression, or resistance to therapy that are regulated by methylation-induced silencing.

  16. RB Loss Promotes Prostate Cancer Metastasis.

    PubMed

    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

    2017-02-15

    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. Cancer Res; 77(4); 982-95. ©2016 AACR.

  17. Urine biomarkers in prostate cancer.

    PubMed

    Ploussard, Guillaume; de la Taille, Alexandre

    2010-02-01

    The deficiencies of serum PSA as a prostate-cancer-specific diagnostic test are well recognized. Thus, the development of novel biomarkers for prostate cancer detection remains an important and exciting challenge. Noninvasive urine-based tests are particularly attractive candidates for large-scale screening protocols, and biomarker discovery programs using urine samples have emerged for detecting and predicting aggressiveness of prostate cancer. Some new biomarkers already outperform serum PSA in the diagnosis of this disease. Currently, the PCA3 (prostate cancer antigen 3) urine test is probably the best adjunct to serum PSA for predicting biopsy outcome, and has proven its clinical relevance by surpassing the predictive abilities of traditional serum biomarkers. New research methods are also emerging, and high-throughput technologies will facilitate high-dimensional biomarker discovery. Future approaches will probably integrate proteomic, transcriptomic and multiplex approaches to detect novel biomarkers, and aim to identify combinations of multiple biomarkers to optimize the detection of prostate cancer. In addition, an unmet need remains for markers that differentiate indolent from aggressive cancers, to better inform treatment decisions.

  18. Proton therapy for prostate cancer.

    PubMed

    Hoppe, Bradford; Henderson, Randal; Mendenhall, William M; Nichols, Romaine C; Li, Zuofeng; Mendenhall, Nancy P

    2011-06-01

    Proton therapy has been used in the treatment of cancer for over 50 years. Due to its unique dose distribution with its spread-out Bragg peak, proton therapy can deliver highly conformal radiation to cancers located adjacent to critical normal structures. One of the important applications of its use is in prostate cancer, since the prostate is located adjacent to the rectum and bladder. Over 30 years of data have been published on the use of proton therapy in prostate cancer; these data have demonstrated high rates of local and biochemical control as well as low rates of urinary and rectal toxicity. Although before 2000 proton therapy was available at only a couple of centers in the United States, several new proton centers have been built in the last decade. With the increased availability of proton therapy, research on its use for prostate cancer has accelerated rapidly. Current research includes explorations of dose escalation, hypofractionation, and patient-reported quality-of-life outcomes. Early results from these studies are promising and will likely help make proton therapy for the treatment of prostate cancer more cost-effective.

  19. Active surveillance for prostate cancer.

    PubMed

    Romero-Otero, Javier; García-Gómez, Borja; Duarte-Ojeda, José M; Rodríguez-Antolín, Alfredo; Vilaseca, Antoni; Carlsson, Sigrid V; Touijer, Karim A

    2016-03-01

    It is worth distinguishing between the two strategies of expectant management for prostate cancer. Watchful waiting entails administering non-curative androgen deprivation therapy to patients on development of symptomatic progression, whereas active surveillance entails delivering curative treatment on signs of disease progression. The objectives of the two management strategies and the patients enrolled in either are different: (i) to review the role of active surveillance as a management strategy for patients with low-risk prostate cancer; and (ii) review the benefits and pitfalls of active surveillance. We carried out a systematic review of active surveillance for prostate cancer in the literature using the National Center for Biotechnology Information's electronic database, PubMed. We carried out a search in English using the terms: active surveillance, prostate cancer, watchful waiting and conservative management. Selected studies were required to have a comprehensive description of the demographic and disease characteristics of the patients at the time of diagnosis, inclusion criteria for surveillance, and a protocol for the patients' follow up. Review articles were included, but not multiple papers from the same datasets. Active surveillance appears to reduce overtreatment in patients with low-risk prostate cancer without compromising cancer-specific survival at 10 years. Therefore, active surveillance is an option for select patients who want to avoid the side-effects inherent to the different types of immediate treatment. However, inclusion criteria for active surveillance and the most appropriate method of monitoring patients on active surveillance have not yet been standardized.

  20. 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.

  1. Prostate cancer: appraisal, coping, and health status.

    PubMed

    Ahmad, Muayyad M; Musil, Carol M; Zauszniewski, Jaclene A; Resnick, Martin I

    2005-10-01

    The purpose of this study was to identify how cognitive appraisal and types of coping affect the health status of men with prostate cancer. Lazarus and Folkman's model of stress and coping guided this correlational, cross-sectional study. The convenience sample was composed of 131 men with prostate cancer who completed the Cognitive Appraisal of Health Scale, the Ways of Coping Checklist, and the Short-Form Health Survey using mailed questionnaires. Participants who appraised more harm or loss experienced worse physical and mental health. When participants perceived their diagnosis as posing more harm or loss or a greater threat, they were more likely to use emotion-focused coping. When the diagnosis was perceived as a challenge, men were more likely to use more problem-focused coping. The findings of this study enable health care providers to be more attentive to the psychosocial needs of prostate cancer patients.

  2. Histological changes caused by meclofenamic acid in androgen independent prostate cancer tumors: evaluation in a mouse model

    PubMed Central

    Delgado-Enciso, Iván; Soriano-Hernández, Alejandro D.; Rodriguez-Hernandez, Alejandrina; Galvan-Salazar, Héctor R.; Montes-Galindo, Daniel A.; Martinez-Martinez, Rafael; Valdez-Velazquez, Laura L.; Gonzalez-Alvarez, Rafael; Espinoza-Gómez, Francisco; Newton-Sanchez, Oscar A.; Lara-Esqueda, Agustín; Guzman-Esquivel, Jose

    2015-01-01

    ABSTRACT Meclofenamic acid is a nonsteroidal anti-inflammatory drug that has shown therapeutic potential for different types of cancers, including androgen-independent prostate neoplasms. The antitumor effect of diverse nonsteroidal anti-inflammatory drugs has been shown to be accompanied by histological and molecular changes that are responsible for this beneficial effect. The objective of the present work was to analyze the histological changes caused by meclofenamic acid in androgen-independent prostate cancer. Tumors were created in a nude mouse model using PC3 cancerous human cells. Meclofenamic acid (10 mg/kg/day; experimental group, n=5) or saline solution (control group, n=5) was administered intraperitoneally for twenty days. Histological analysis was then carried out on the tumors, describing changes in the cellular architecture, fibrosis, and quantification of cellular proliferation and tumor vasculature. Meclofenamic acid causes histological changes that indicate less tumor aggression (less hypercellularity, fewer atypical mitoses, and fewer nuclear polymorphisms), an increase in fibrosis, and reduced cellular proliferation and tumor vascularity. Further studies are needed to evaluate the molecular changes that cause the beneficial and therapeutic effects of meclofenamic acid in androgen-independent prostate cancer. PMID:26689527

  3. Serum Phospholipid Fatty Acids and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial

    PubMed Central

    Brasky, Theodore M.; Till, Cathee; White, Emily; Neuhouser, Marian L.; Song, Xiaoling; Goodman, Phyllis; Thompson, Ian M.; King, Irena B.; Albanes, Demetrius; Kristal, Alan R.

    2011-01-01

    Inflammation may be involved in prostate cancer development and progression. This study examined the associations between inflammation-related phospholipid fatty acids and the 7-year-period prevalence of prostate cancer in a nested case-control analysis of participants, aged 55–84 years, in the Prostate Cancer Prevention Trial during 1994–2003. Cases (n = 1,658) were frequency matched to controls (n = 1,803) on age, treatment, and prostate cancer family history. Phospholipid fatty acids were extracted from serum, and concentrations of ω-3, ω-6, and trans-fatty acids (TFAs) were expressed as proportions of the total. Logistic regression models estimated odds ratios and 95% confidence intervals of associations of fatty acids with prostate cancer by grade. No fatty acids were associated with low-grade prostate cancer risk. Docosahexaenoic acid was positively associated with high-grade disease (quartile 4 vs. 1: odds ratio (OR) = 2.50, 95% confidence interval (CI): 1.34, 4.65); TFA 18:1 and TFA 18:2 were linearly and inversely associated with risk of high-grade prostate cancer (quartile 4 vs. 1: TFA 18:1, OR = 0.55, 95% CI: 0.30, 0.98; TFA 18:2, OR = 0.48, 95% CI: 0.27, 0.84). The study findings are contrary to those expected from the pro- and antiinflammatory effects of these fatty acids and suggest a greater complexity of effects of these nutrients with regard to prostate cancer risk. PMID:21518693

  4. Development of a Gene Therapy Trial for Metastatic Prostate Cancer

    DTIC Science & Technology

    2008-01-01

    Clinician-Scientists Drs. Gardner, Hanh, and Ko representing a genitourinary oncologic surgeon , genitourinary oncologist and genitourinary radiation...Osteocalcin promoter-based toxic gene therapy for the treatment of osteosarcoma in experimental models. Cancer Res 1996; 56: 4614–4619. 10 Springer CJ...vector, Ad-OC-E1a, to cotarget prostate cancer and bone stroma in an experimental model of androgen- independent prostate cancer bone metastasis . Cancer

  5. Reconstructing the Prostate Cancer Transcriptional Regulatory Network

    DTIC Science & Technology

    2010-07-01

    TITLE: Reconstructing the prostate cancer transcriptional regulatory network PRINCIPAL INVESTIGATOR: Keyan Salari...CONTRACT NUMBER 4. TITLE AND SUBTITLE Reconstructing the prostate cancer transcriptional regulatory network 5b. GRANT NUMBER W81XWH-09-1...of this study is to reconstruct the prostate cancer transcriptional regulatory network and to experimentally validate novel, clinically-relevant

  6. 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.…

  7. 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.…

  8. Role of Obesity in Prostate Cancer Development

    DTIC Science & Technology

    2011-04-01

    prostate cancer development in this model. A second experiment was conducted using a prostate cancer cell line developed from a TRAMP mouse tumor, TRAMP...antibodies used are shown along the left hand side. 11 Study using TRAMP-C2 Cells Because of the difficulties with GTG injections described above we...Lynch,C.F., Rubenstein,L.M., Lemke,J.H., Cohen,M.B., Lubaroff,D.M., and Wallace,R.B. (1997) Association of smoking , body mass, and physical activity

  9. Serum Retinol and Risk of Prostate Cancer

    PubMed Central

    Mondul, Alison M.; Watters, Joanne L.; Männistö, Satu; Weinstein, Stephanie J.; Snyder, Kirk; Virtamo, Jarmo; Albanes, Demetrius

    2011-01-01

    Greater exposure to retinol (vitamin A) may prevent prostate cancer, although under some conditions it could promote cell growth and de-differentiation. The authors prospectively examined prostate cancer risk and serum retinol levels, measured by using high-performance liquid chromatography, at baseline (n = 29,104) and after 3 years (n = 22,843) in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Cox proportional hazards models were used to estimate the relative risk of total (n = 2,041) and aggressive (n = 461) prostate cancer by quintiles of baseline and 3-year serum retinol concentrations and by change in serum retinol levels from baseline to 3 years. Men with higher retinol concentrations at baseline were more likely to develop prostate cancer (quintile 5 vs. quintile 1 hazard ratio = 1.19, 95% confidence interval: 1.03, 1.36; Ptrend = 0.009). The results were similar for aggressive disease. Joint categorization based on baseline and 3-year retinol levels showed that men who were in the highest quintile at both time points had the greatest increased risk (baseline/3-year quintile 5/quintile 5 vs. quintile 1/quintile 1 hazard ratio = 1.31, 95% confidence interval: 1.08, 1.59). In this largest study to date of vitamin A status and subsequent risk of prostate cancer, higher serum retinol was associated with elevated risk, with sustained high exposure conferring the greatest risk. Future studies may clarify the underlying biologic mechanisms of the retinol-prostate cancer association. PMID:21389041

  10. Serum retinol and risk of prostate cancer.

    PubMed

    Mondul, Alison M; Watters, Joanne L; Männistö, Satu; Weinstein, Stephanie J; Snyder, Kirk; Virtamo, Jarmo; Albanes, Demetrius

    2011-04-01

    Greater exposure to retinol (vitamin A) may prevent prostate cancer, although under some conditions it could promote cell growth and de-differentiation. The authors prospectively examined prostate cancer risk and serum retinol levels, measured by using high-performance liquid chromatography, at baseline (n = 29,104) and after 3 years (n = 22,843) in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Cox proportional hazards models were used to estimate the relative risk of total (n = 2,041) and aggressive (n = 461) prostate cancer by quintiles of baseline and 3-year serum retinol concentrations and by change in serum retinol levels from baseline to 3 years. Men with higher retinol concentrations at baseline were more likely to develop prostate cancer (quintile 5 vs. quintile 1 hazard ratio = 1.19, 95% confidence interval: 1.03, 1.36; P(trend) = 0.009). The results were similar for aggressive disease. Joint categorization based on baseline and 3-year retinol levels showed that men who were in the highest quintile at both time points had the greatest increased risk (baseline/3-year quintile 5/quintile 5 vs. quintile 1/quintile 1 hazard ratio = 1.31, 95% confidence interval: 1.08, 1.59). In this largest study to date of vitamin A status and subsequent risk of prostate cancer, higher serum retinol was associated with elevated risk, with sustained high exposure conferring the greatest risk. Future studies may clarify the underlying biologic mechanisms of the retinol-prostate cancer association.

  11. Prostate cancer brachytherapy: guidelines overview.

    PubMed

    Wojcieszek, Piotr; Białas, Brygida

    2012-06-01

    Prostate cancer, due to wide availability of PSA tests, is very often diagnosed in early stage, nowadays. This makes management of this disease even harder in every day oncology care. There is a wide range of treatment options including surgery, radiotherapy and active surveillance, but essential question is which treatment patient and oncologist should decide for. Due to recent publication of Prostate Cancer Results Study Group, in which brachytherapy is one of supreme curative options for prostate cancer, we decided to overview most present european and north american recommendations. National Comprehensive Cancer Network, American Society for Radiation Oncology, American Brachytherapy Society, European Association of Urology and Groupe Européen de Curiethérapie of European Society for Therapeutic Radiation Oncology guidelines are overviewed, particularly focusing on HDR and LDR brachytherapy.

  12. Prostate cancer brachytherapy: guidelines overview

    PubMed Central

    Białas, Brygida

    2012-01-01

    Prostate cancer, due to wide availability of PSA tests, is very often diagnosed in early stage, nowadays. This makes management of this disease even harder in every day oncology care. There is a wide range of treatment options including surgery, radiotherapy and active surveillance, but essential question is which treatment patient and oncologist should decide for. Due to recent publication of Prostate Cancer Results Study Group, in which brachytherapy is one of supreme curative options for prostate cancer, we decided to overview most present european and north american recommendations. National Comprehensive Cancer Network, American Society for Radiation Oncology, American Brachytherapy Society, European Association of Urology and Groupe Européen de Curiethérapie of European Society for Therapeutic Radiation Oncology guidelines are overviewed, particularly focusing on HDR and LDR brachytherapy. PMID:23349655

  13. Methylselenium and Prostate Cancer Apoptosis

    DTIC Science & Technology

    2005-02-01

    15. NUMBER OF PAGES Selenium, methylselenol , prostate cancer chemoprevention, apoptosis 15 16. PRICE CODE 17. SECURITY CLASSIFICATION 18. SECURITY...that Methylselenol has been implicated as an active metabolite inhibit one or more steps in the natural history of prostate for the anticancer effect of...in PCa chemoprevention and therapy activity) for their apoptosis responses to the methylselenol by selenium compounds (8). Methylselenol has been impli

  14. Predictive models of toxicity with external radiotherapy for prostate cancer: clinical issues.

    PubMed

    Valdagni, Riccardo; Rancati, Tiziana; Fiorino, Claudio

    2009-07-01

    The objective of the current study was to analyze the state of the art and present limitations of available predictive clinical models (when available) estimating the risk of genitourinary tract and small bowel complications, erectile dysfunction, and acute and late symptoms of the rectal syndrome caused by prostate cancer external irradiation. An analysis of the literature indicated that very limited attention has been devoted to the development of "integrated," patient-tailored, user-friendly, and clinically usable tools for the prediction of external beam radiotoxicity. In this article, the authors reported on the multivariate correlation between late genitourinary and gastrointestinal toxicities and clinical/dosimetric risk factors, as well as on the first set of nomograms developed to predict acute and late rectal side effects. At the present state of knowledge, the use of nomograms as predictive instruments of radiotoxicity appears to be particularly attractive for several main reasons. They are "user friendly" and easily developed using the results of multivariate analyses, as they weigh the combined effects of multiple independent factors found to be correlated with the selected clinical endpoint. The integrated evaluation of clinical and dosimetric parameters in the single patient can help to provide a tailored probability of the specific outcome considered. Predicting a high probability of toxicity could avoid unnecessary daily costs for the individual patient in terms of quality of life modification during and after treatment, helping patients in the decision-making process of choosing the best individual, quality of life-related treatment, and clinicians in better tailoring the treatment to patient's characteristics. Cancer 2009;115(13 suppl):3141-9. (c) 2009 American Cancer Society.

  15. Natural history of prostate cancer.

    PubMed

    Estebanez, Javier; Teyrouz, Antoin; Gutierrez, Miguel Angel; Linazasoro, Ione; Belloso, Jon; Cano, Carlos; Peralta, Jose Maria; Sanz, Juan Pablo

    2014-06-01

    Prostatic cancer can be a silent tumor, with no symptoms remaining undetectable throughout life . But when it keeps growing, enough to produce symptoms such as bladder neck obstruction, invasion of adjacent organs or distant metastasis, curative treatment is usually impossible. Since PSA emerges, data shows a dramatic increasing in the diagnosis of prostatic cancer, specially low risk tumor. Since then, We are wondering which tumors are suitable to be treated and which ones remain asymptomatic without treatment. Analysing the natural history of prostate cancer, helps us to choose the best atitude treating the tumor, this subjet has been in constant discusión in the last decade. Our article consistes of a reviewing the main publications treating natural history of prostate cancer in prehyphen;and post-PSA era. The indicated studied suggest that most prostate tumors diagnosed today are low grade cancer, as a result with a low mortality. This conclusión shows us the importance of modifying the algorithm of treatment of these tumors.

  16. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model By Targeting 15-Lipoxygenase-1

    DTIC Science & Technology

    2011-02-01

    chemoprevention studies. Diets rich in either omega (ω)-3 or ω-6 polyunsaturated fatty acids ( PUFAs ) directly impact PCa tumor growth. Furthermore, the FLiMP...polyunsaturated fatty acids ( PUFAs ), 15-lipoxygenase-1, cyclooxygenase, prostate cancer, Array, Genes. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION...observed) and, (3) Our study in year 2 provided mechanistic roles of omega (ω)-3 fatty acids in slowing PCa growth by altering ω-6/ ω-3 ratios via diet

  17. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1

    DTIC Science & Technology

    2012-02-01

    chemoprevention studies. Diets rich in either omega (ω)-3 or ω-6 polyunsaturated fatty acids ( PUFAs ) directly impact PCa tumor growth. Furthermore... acids effects on PIN development. 15. SUBJECT TERMS Diet, polyunsaturated fatty acids ( PUFAs ), 15-lipoxygenase-1, cyclooxygenase, prostate cancer...compared to FLiMP+/+ mice fed a normal diet (PIN observed) and, (3) Our study in year 2 provided mechanistic roles of omega (ω)-3 fatty acids in slowing

  18. Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval

    DTIC Science & Technology

    2015-10-01

    sponsored phase II treatment trial conducted in the Prostate Cancer Clinical Trials Consortium. The third aim is to conduct literature reviews and...10.1016/j.eururo.2014.02.013. PMID: 24631409 Aim 3 To conduct literature reviews and moderate a consensus meeting, with input from investigators...complete, with each resulting in a peer- reviewed manuscript published in high impact journals. PUBLICATIONS, ABSTRACTS, AND PRESENTATIONS Basch E

  19. Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1

    DTIC Science & Technology

    2009-02-01

    in either omega (ω)-3 or ω-6 polyunsaturated fatty acids (PUFAs) directly impact PCa tumor growth. Furthermore, the FLiMP mice, which overexpress ...monounsaturated fatty acid pathway enzyme, Δ-9-desaturase which is a member in the fatty acid synthase (FASN) pathway, increased in tumors from SDA... Overexpression of 15-lipoxygenase-1 in PC-3 human prostate cancer cells increases tumorigenesis. Carcinogenesis, 22, 1765-73. 6. Ziboh A and VangK

  20. Deconvoluting the Complexity of Bone Metastatic Prostate Cancer via Computational Modeling

    DTIC Science & Technology

    2016-09-01

    2. KEYWORDS: Provide a brief list of keywords (limit to 20 words). TGFβ- Transforming Growth Factor Beta Prostate Cancer (PCa) to Bone...intensity for each clonal population . (c-f) In silico simulations (n 24/group) were performed under control or TGF inhibition (80% efficacy) post- and pre...treatment conditions. Clonal population was measured at Day 100 (left y- axis) and Day 250 (right y-axis). The project provided the PI with

  1. SOX4 is essential for prostate tumorigenesis initiated by PTEN ablation | Office of Cancer Genomics

    Cancer.gov

    Understanding remains incomplete of the mechanisms underlying initiation and progression of prostate cancer, the most commonly diagnosed cancer in American men. The transcription factor SOX4 is overexpressed in many human cancers, including prostate cancer, suggesting it may participate in prostate tumorigenesis. In this study, we investigated this possibility by genetically deleting Sox4 in a mouse model of prostate cancer initiated by loss of the tumor suppressor Pten.

  2. Detection of DNA viruses in prostate cancer.

    PubMed

    Smelov, Vitaly; Bzhalava, Davit; Arroyo Mühr, Laila Sara; Eklund, Carina; Komyakov, Boris; Gorelov, Andrey; Dillner, Joakim; Hultin, Emilie

    2016-04-28

    We tested prostatic secretions from men with and without prostate cancer (13 cases and 13 matched controls) or prostatitis (18 cases and 18 matched controls) with metagenomic sequencing. A large number (>200) of viral reads was only detected among four prostate cancer cases (1 patient each positive for Merkel cell polyomavirus, JC polyomavirus and Human Papillomavirus types 89 or 40, respectively). Lower numbers of reads from a large variety of viruses were detected in all patient groups. Our knowledge of the biology of the prostate may be furthered by the fact that DNA viruses are commonly shed from the prostate and can be readily detected by metagenomic sequencing of expressed prostate secretions.

  3. National Cancer Institute Prostate Cancer Genetics Workshop.

    PubMed

    Catalona, William J; Bailey-Wilson, Joan E; Camp, Nicola J; Chanock, Stephen J; Cooney, Kathleen A; Easton, Douglas F; Eeles, Rosalind A; FitzGerald, Liesel M; Freedman, Matthew L; Gudmundsson, Julius; Kittles, Rick A; Margulies, Elliott H; McGuire, Barry B; Ostrander, Elaine A; Rebbeck, Timothy R; Stanford, Janet L; Thibodeau, Stephen N; Witte, John S; Isaacs, William B

    2011-05-15

    Compelling evidence supports a genetic component to prostate cancer susceptibility and aggressiveness. Recent genome-wide association studies have identified more than 30 single-nucleotide polymorphisms associated with prostate cancer susceptibility. It remains unclear, however, whether such genetic variants are associated with disease aggressiveness--one of the most important questions in prostate cancer research today. To help clarify this and substantially expand research in the genetic determinants of prostate cancer aggressiveness, the first National Cancer Institute Prostate Cancer Genetics Workshop assembled researchers to develop plans for a large new research consortium and patient cohort. The workshop reviewed the prior work in this area and addressed the practical issues in planning future studies. With new DNA sequencing technology, the potential application of sequencing information to patient care is emerging. The workshop, therefore, included state-of-the-art presentations by experts on new genotyping technologies, including sequencing and associated bioinformatics issues, which are just beginning to be applied to cancer genetics. ©2011 AACR

  4. LuCaP Prostate Cancer Patient-Derived Xenografts Reflect the Molecular Heterogeneity of Advanced Disease an--d Serve as Models for Evaluating Cancer Therapeutics.

    PubMed

    Nguyen, Holly M; Vessella, Robert L; Morrissey, Colm; Brown, Lisha G; Coleman, Ilsa M; Higano, Celestia S; Mostaghel, Elahe A; Zhang, Xiaotun; True, Lawrence D; Lam, Hung-Ming; Roudier, Martine; Lange, Paul H; Nelson, Peter S; Corey, Eva

    2017-05-01

    Metastatic prostate cancer is a common and lethal disease for which there are no therapies that produce cures or long-term durable remissions. Clinically relevant preclinical models are needed to increase our understanding of biology of this malignancy and to evaluate new agents that might provide effective treatment. Our objective was to establish and characterize patient-derived xenografts (PDXs) from advanced prostate cancer (PC) for investigation of biology and evaluation of new treatment modalities. Samples of advanced PC obtained from primary prostate cancer obtained at surgery or from metastases collected at time of death were implanted into immunocompromised mice to establish PDXs. Established PDXs were propagated in vivo. Genomic, transcriptomic, and STR profiles were generated. Responses to androgen deprivation and docetaxel in vivo were characterized. We established multiple PDXs (LuCaP series), which represent the major genomic and phenotypic features of the disease in humans, including amplification of androgen receptor, PTEN deletion, TP53 deletion and mutation, RB1 loss, TMPRSS2-ERG rearrangements, SPOP mutation, hypermutation due to MSH2/MSH6 genomic aberrations, and BRCA2 loss. The PDX models also exhibit variation in intra-tumoral androgen levels. Our in vivo results show heterogeneity of response to androgen deprivation and docetaxel, standard therapies for advanced PC, similar to the responses of patients to these treatments. The LuCaP PDX series reflects the diverse molecular composition of human castration-resistant PC and allows for hypothesis-driven cause-and-effect studies of mechanisms underlying treatment response and resistance. Prostate 77: 654-671, 2017. © 2017 The Authors. The Prostate Published by Wiley Periodicals, Inc. © 2017 The Authors. The Prostate Published by Wiley Periodicals, Inc.

  5. Circulating 25-Hydroxyvitamin D and Prostate Cancer Survival.

    PubMed

    Mondul, Alison M; Weinstein, Stephanie J; Moy, Kristin A; Männistö, Satu; Albanes, Demetrius

    2016-04-01

    Recent epidemiologic evidence suggests that higher circulating vitamin D does not protect against prostate cancer and, in fact, may increase the risk of developing this malignancy. However, few studies have examined the most clinically relevant outcome, prostate cancer mortality. We examined prediagnostic serum 25-hydroxy-vitamin D (25(OH)D) and prostate cancer survival in a cohort of 1,000 cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. During 23 years of follow-up, 363 men died from their disease. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of death from prostate cancer by season-specific quintile of 25(OH)D. Multivariable models were adjusted for age, physical activity, cigarettes per day, and family history of prostate cancer. Men with higher serum 25(OH)D were less likely to die from their prostate cancer (Q5 vs. Q1 HR, 0.72; 95% CI, 0.52-0.99; Ptrend = 0.006). This finding was independent of stage or grade at diagnosis and appeared restricted to men who survived longer (survived <3.3 years: Q5 vs. Q1 HR, 0.95; 95% CI, 0.61-1.50; Ptrend, 0.53; survived ≥3.3 years: Q5 vs. Q1 HR, 0.53; 95% CI, 0.34-0.85; Ptrend, 0.0002). In this population of men diagnosed with prostate cancer, higher serum 25(OH)D years prior to diagnosis was associated with longer prostate cancer survival. In light of inconsistent evidence regarding the role of vitamin D in the development of prostate cancer, the present findings regarding the most clinically relevant prostate cancer outcome, disease-specific mortality, could have important public health implications. Cancer Epidemiol Biomarkers Prev; 25(4); 665-9. ©2016 AACR. ©2016 American Association for Cancer Research.

  6. Targeting the Neural Microenvironment in Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    studies have shown that chemical or surgical ablation of nerves inhibits tumorigenesis and metastasis in both xenograft and transgenic mouse models...GFRA1 and GDNF in human prostate cancer tissues including localized, metastatic and castrate resistant with quantitation (months 4- 36) We are

  7. Estrogens and Antiestrogens in Prostate Cancer

    DTIC Science & Technology

    2003-01-01

    vitamin E, and lycopene protect against prostate cancer. The project will determine the magnitude of the protective activity of these antioxidants...in particular estrogen- induced animal model, the efficacies of three dietary antioxidants (vitamin E, selenium and lycopene ), singularly or in

  8. Reduction by coffee consumption of prostate cancer risk: Evidence from the Moli-sani cohort and cellular models.

    PubMed

    Pounis, George; Tabolacci, Claudio; Costanzo, Simona; Cordella, Martina; Bonaccio, Marialaura; Rago, Livia; D'Arcangelo, Daniela; Filippo Di Castelnuovo, Augusto; de Gaetano, Giovanni; Donati, Maria Benedetta; Iacoviello, Licia; Facchiano, Francesco

    2017-07-01

    Meta-analytic data on the effect of coffee in prostate cancer risk are controversial. Caffeine as a bioactive compound of coffee has not yet been studied in deep in vitro. Our study aimed at evaluating in a population cohort the effect of Italian-style coffee consumption on prostate cancer risk and at investigating in vitro the potential antiproliferative and antimetastatic activity of caffeine on prostate cancer cell lines. 6,989 men of the Moli-sani cohort aged ≥50 years were followed for a mean of 4.24 ± 1.35 years and 100 new prostate cancer cases were identified. The European Prospective Investigation into Cancer and Nutrition-Food Frequency Questionnaire was used for the dietary assessment and the evaluation of Italian-style coffee consumption. Two human prostate cancer cell lines, PC-3 and DU145, were tested with increasing concentrations of caffeine, and their proliferative/metastatic features were evaluated. The newly diagnosed prostate cancer participants presented lower coffee consumption (60.1 ± 51.3 g/day) compared to the disease-free population (74.0 ± 51.7 g/day) (p < 0.05). Multiadjusted analysis showed that the subjects at highest consumption (>3 cups/day) had 53% lower prostate cancer risk as compared to participants at the lowest consumption (0-2 cups/day) (p = 0.02). Both human prostate cancer cell lines treated with caffeine showed a significant reduction in their proliferative and metastatic behaviors (p < 0.05). In conclusion, reduction by Italian-style coffee consumption of prostate cancer risk (>3 cups/day) was observed in epidemiological level. Caffeine appeared to exert both antiproliferative and antimetastatic activity on two prostate cancer cell lines, thus providing a cellular confirmation for the cohort study results. © 2017 UICC.

  9. Prostatitis, Sexually Transmitted Diseases, and Prostate Cancer: The California Men's Health Study

    PubMed Central

    Cheng, Iona; Witte, John S.; Jacobsen, Steven J.; Haque, Reina; Quinn, Virginia P.; Quesenberry, Charles P.; Caan, Bette J.; Van Den Eeden, Stephen K.

    2010-01-01

    Background Prostatitis and sexually transmitted diseases (STDs) have been positively associated with prostate cancer in previous case-control studies. However, results from recent prospective studies have been inconclusive. Methodogy/Principal Findings We investigated the association between prostatitis, STDs, and prostate cancer among African American, Asian American, Latino, and White participants of the California Men's Health Study. Our analysis included 68,675 men, who completed a detailed baseline questionnaire in 2002–2003. We identified 1,658 incident prostate cancer cases during the follow-up period to June 30, 2006. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals. Overall, men having a history of prostatitis had an increased risk of prostate cancer than men with no history (RR = 1.30; 95% CI: 1.10–1.54). Longer duration of prostatitis symptoms was also associated with an increased risk of prostate cancer (P trend = 0.003). In addition, among men screened for prostate cancer (1 or 2 PSA tests), a non-significant positive association was observed between prostatitis and prostate cancer (RR = 1.10; 95% CI: 0.75–1.63). STDs were not associated with overall prostate cancer risk. In racial/ethnic stratified analysis, Latinos reporting any STDs had an increased risk of disease than those with no STDs (RR = 1.43; 95% CI: 1.07–1.91). Interestingly, foreign-born Latinos displayed a larger risk associated with STDs (RR = 1.87; 95% CI: 1.16–3.02) than U.S. born Latinos (RR = 1.15; 95% CI: 0.76–3.02). Conclusion In summary, results from this prospective study suggest that prostatitis and STDs may be involved in prostate cancer susceptibility. While we cannot rule out the possible influence of incidental detection, future studies are warranted to further investigate the role of infectious agents related to prostatitis and STDs in prostate cancer development. PMID:20090948

  10. ING4 Loss in Prostate Cancer Progression

    DTIC Science & Technology

    2016-10-01

    TMA, mouse model , human model . 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON...differentiation, Myc, ING4, chromatin, integrins, Erg, Pten, Miz1, CREB, Notch, p38, prostate cancer oncogenesis, TMA, mouse model , human model 3...of hits in model Months 28-34* Milestone #2: Prepare manuscript for publication Months 35-36 Specific Aim 2: Determine how loss of ING4 impacts

  11. Prostate cancers detected on repeat prostate biopsies show spatial distributions that differ from those detected on the initial biopsies.

    PubMed

    Eminaga, Okyaz; Hinkelammert, Reemt; Abbas, Mahmoud; Titze, Ulf; Eltze, Elke; Bettendorf, Olaf; Wötzel, Fabian; Bögemann, Martin; Semjonow, Axel

    2015-07-01

    To evaluate the spatial distribution of prostate cancer detected at a single positive biopsy (PBx) and a repeat PBx (rPBx). We evaluated 533 consecutive men diagnosed with prostate cancer who underwent radical prostatectomy using a clinical map document based on XML (cMDX©)-based map model of the prostate. We determined the number of cancer foci, relative tumour volume, Gleason score, zone of origin, localisation, and pathological stage after stratification according to the number of PBx sessions (PBx vs rPBx). The distribution of 3966 prostate cancer foci was analysed and visualised on heat maps. The colour gradient of the heat map was reduced to six colours representing the frequency classification of prostate cancer using an image posterisation effect. Additionally, the spatial distribution of organ-confined prostate cancer between PBx and rPBx was evaluated. Prostate cancer diagnosed on PBx was mostly localised to the apical portion and the peripheral zone of the prostate. Prostate cancer diagnosed on rPBx was more frequently found in the anterior portion and the base of the prostate. Organ-confined prostate cancer foci were mostly localised in the dorsolateral zone of the prostate in men at PBx, whereas men at rPBx had more prostate cancer foci in the anterior portion. The spatial distribution of prostate cancer with rPBx differs significantly from the spatial distribution of prostate cancer with PBx. The whole anterior portion of the prostate should be considered by rPBx. © 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.

  12. Selection and identification of ligand peptides targeting a model of castrate-resistant osteogenic prostate cancer and their receptors.

    PubMed

    Mandelin, Jami; Cardó-Vila, Marina; Driessen, Wouter H P; Mathew, Paul; Navone, Nora M; Lin, Sue-Hwa; Logothetis, Christopher J; Rietz, Anna Cecilia; Dobroff, Andrey S; Proneth, Bettina; Sidman, Richard L; Pasqualini, Renata; Arap, Wadih

    2015-03-24

    We performed combinatorial peptide library screening in vivo on a novel human prostate cancer xenograft that is androgen-independent and induces a robust osteoblastic reaction in bonelike matrix and soft tissue. We found two peptides, PKRGFQD and SNTRVAP, which were enriched in the tumors, targeted the cell surface of androgen-independent prostate cancer cells in vitro, and homed to androgen receptor-null prostate cancer in vivo. Purification of tumor homogenates by affinity chromatography on these peptides and subsequent mass spectrometry revealed a receptor for the peptide PKRGFQD, α-2-macroglobulin, and for SNTRVAP, 78-kDa glucose-regulated protein (GRP78). These results indicate that GRP78 and α-2-macroglobulin are highly active in osteoblastic, androgen-independent prostate cancer in vivo. These previously unidentified ligand-receptor systems should be considered for targeted drug development against human metastatic androgen-independent prostate cancer.

  13. The Prostate Cancer Biorepository Network (PCBN)

    DTIC Science & Technology

    2016-10-01

    embedded material and tissue microarrays (TMAs)), prostate cancer patient derived xenografts (PDX) and derived specimens ( DNA and RNA) from prostate...derived RNA and DNA where required. Specimens were made available to prostate cancer researchers through the PCBN. 15. SUBJECT TERMS Biorepository...and derived specimens ( DNA and RNA) from prostate cancer patients; these specimens are linked to clinical and outcome data and supported by an

  14. Comparison of prostate-specific promoters and the use of PSP-driven virotherapy for prostate cancer.

    PubMed

    Lu, Yi; Zhang, Yu; Chang, Guimin; Zhang, Jun

    2013-01-01

    Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer deaths in men today. Although virus-based gene therapy is a promising strategy to combat advanced prostate cancer, its current effectiveness is limited partially due to inefficient cellular transduction in vivo. To overcome this obstacle, conditional oncolytic viruses (such as conditional replication adenovirus (CRAD)) are developed to specifically target prostate without (or with minimal) systemic toxicity due to viral self-replication. In this study, we have analyzed and compared three prostate-specific promoters (PSA, probasin, and MMTV LTR) for their specificity and activity both in vitro and in vivo. Both mice model with xenograft prostate tumor model and canine model were used. The best PSP was selected to construct a prostate-specific oncolytic adenovirus (CRAD) by controlling the adenoviral E1 region. The efficacy and specificity of CRAD on prostate cancer cells were examined in cell culture and animal models.

  15. Metastatic Prostate Cancer of Hand

    PubMed Central

    Oshima, Koji; Ishimaru, Daichi; Nishimoto, Yutaka; Ohno, Yoshiyuki; Hirakawa, Akihiro; Miyazaki, Tatsuhiko; Akiyama, Haruhiko

    2016-01-01

    Soft tissue metastases of prostate cancer to other sites are extremely rare, and, to our best knowledge, there have been no reports of metastasis to soft tissue of the hand. A 63-year-old man was diagnosed with prostatic cancer. During treatment, bone and soft tissue metastases to the right hand, appearing in the first web space, were observed. The tumor was resected, along with both the first and second metacarpal bones. The thumb was reconstructed by pollicization of the remaining index finger, enabling the patient to use the pollicized thumb for activities of daily living. This is the first case report of prostate cancer metastasizing to the soft tissue in hand. After wide resection, pollicization was able to reconstruct a functional hand and thumb. PMID:27843661

  16. Detection of prostate cancer on histopathology using color fractals and Probabilistic Pairwise Markov models.

    PubMed

    Yu, Elaine; Monaco, James P; Tomaszewski, John; Shih, Natalie; Feldman, Michael; Madabhushi, Anant

    2011-01-01

    In this paper we present a system for detecting regions of carcinoma of the prostate (CaP) in H&E stained radical prostatectomy specimens using the color fractal dimension. Color textural information is known to be a valuable characteristic to distinguish CaP from benign tissue. In addition to color information, we know that cancer tends to form contiguous regions. Our system leverages the color staining information of histology as well as spatial dependencies. The color and textural information is first captured using color fractal dimension. To incorporate spatial dependencies, we combine the probability map constructed via color fractal dimension with a novel Markov prior called the Probabilistic Pairwise Markov Model (PPMM). To demonstrate the capability of this CaP detection system, we applied the algorithm to 27 radical prostatectomy specimens from 10 patients. A per pixel evaluation was conducted with ground truth provided by an expert pathologist using only the color fractal feature first, yielding an area under the receiver operator characteristic curve (AUC) curve of 0.790. In conjunction with a Markov prior, the resultant color fractal dimension + Markov random field (MRF) classifier yielded an AUC of 0.831.

  17. Aurora A regulates expression of AR-V7 in models of castrate resistant prostate cancer

    PubMed Central

    Jones, Dominic; Noble, Martin; Wedge, Steve R.; Robson, Craig N.; Gaughan, Luke

    2017-01-01

    Androgen receptor variants (AR-Vs) provide a mechanism of therapy evasion in castrate-resistant prostate cancer (CRPC), yet mechanisms of regulation remain largely unknown. Here we investigate the role of Aurora A kinase on AR-Vs in models of CRPC and show depletion of Aurora A reduces AR-V target gene expression. Importantly, knockdown of Aurora A reconfigures splicing of AR pre-mRNA to discriminately down-regulate synthesis of AR-V transcripts, including AR-V7, without effecting full-length AR mRNA; and as a consequence, AR-V-driven proliferation and survival of CRPC cells is markedly reduced. Critically, these effects are reproduced by Aurora A inhibition. We show that Aurora A levels increase in advanced disease and AURKA is an AR-V target gene demonstrating a positive feedback mechanism of androgenic signalling in CRPC. In all, our data suggests that Aurora A plays a pivotal role in regulation of AR-V7 expression and represents a new therapeutic target in CRPC. PMID:28205582

  18. Aurora A regulates expression of AR-V7 in models of castrate resistant prostate cancer.

    PubMed

    Jones, Dominic; Noble, Martin; Wedge, Steve R; Robson, Craig N; Gaughan, Luke

    2017-02-16

    Androgen receptor variants (AR-Vs) provide a mechanism of therapy evasion in castrate-resistant prostate cancer (CRPC), yet mechanisms of regulation remain largely unknown. Here we investigate the role of Aurora A kinase on AR-Vs in models of CRPC and show depletion of Aurora A reduces AR-V target gene expression. Importantly, knockdown of Aurora A reconfigures splicing of AR pre-mRNA to discriminately down-regulate synthesis of AR-V transcripts, including AR-V7, without effecting full-length AR mRNA; and as a consequence, AR-V-driven proliferation and survival of CRPC cells is markedly reduced. Critically, these effects are reproduced by Aurora A inhibition. We show that Aurora A levels increase in advanced disease and AURKA is an AR-V target gene demonstrating a positive feedback mechanism of androgenic signalling in CRPC. In all, our data suggests that Aurora A plays a pivotal role in regulation of AR-V7 expression and represents a new therapeutic target in CRPC.

  19. Systems modeling of anti-apoptotic pathways in prostate cancer: psychological stress triggers a synergism pattern switch in drug combination therapy.

    PubMed

    Sun, Xiaoqiang; Bao, Jiguang; Nelson, Kyle C; Li, King Chuen; Kulik, George; Zhou, Xiaobo

    2013-01-01

    Prostate cancer patients often have increased levels of psychological stress or anxiety, but the molecular mechanisms underlying the interaction between psychological stress and prostate cancer as well as therapy resistance have been rarely studied and remain poorly understood. Recent reports show that stress inhibits apoptosis in prostate cancer cells via epinephrine/beta2 adrenergic receptor/PKA/BAD pathway. In this study, we used experimental data on the signaling pathways that control BAD phosphorylation to build a dynamic network model of apoptosis regulation in prostate cancer cells. We then compared the predictive power of two different models with or without the role of Mcl-1, which justified the role of Mcl-1 stabilization in anti-apoptotic effects of emotional stress. Based on the selected model, we examined and quantitatively evaluated the induction of apoptosis by drug combination therapies. We predicted that the combination of PI3K inhibitor LY294002 and inhibition of BAD phosphorylation at S112 would produce the best synergistic effect among 8 interventions examined. Experimental validation confirmed the effectiveness of our predictive model. Moreover, we found that epinephrine signaling changes the synergism pattern and decreases efficacy of combination therapy. The molecular mechanisms responsible for therapeutic resistance and the switch in synergism were explored by analyzing a network model of signaling pathways affected by psychological stress. These results provide insights into the mechanisms of psychological stress signaling in therapy-resistant cancer, and indicate the potential benefit of reducing psychological stress in designing more effective therapies for prostate cancer patients.

  20. Prostate Cancer Research Training Program

    DTIC Science & Technology

    2014-05-01

    institutions. A major project in the lab is targeted therapy of prostate cancer using PSMA-guided aptamers. Prabhat Goswami, PhD; Professor...derived dendritic cell (DC) and T cell functional deficiencies. Long-term goals are to develop novel, immune-based therapies for advanced solid tumors...and radiolabeling of peptides and small molecules for small molecule cancer therapy , molecular imaging, and radionuclide therapy for cancer. He

  1. The Prostate Health Index Selectively Identifies Clinically Significant Prostate Cancer

    PubMed Central

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

    2015-01-01

    Purpose The Prostate Health Index (phi) is a new test combining total, free and [-2]proPSA into a single score. It was recently approved by the FDA and is now commercially available in the U.S., Europe and Australia. We investigate whether phi improves specificity for detecting clinically significant prostate cancer and can help reduce prostate cancer over diagnosis. Materials and Methods From a multicenter prospective trial we identified 658 men age 50 years or older with prostate specific antigen 4 to 10 ng/ml and normal digital rectal examination who underwent prostate biopsy. In this population we compared the performance of prostate specific antigen, % free prostate specific antigen, [-2]proPSA and phi to predict biopsy results and, specifically, the presence of clinically significant prostate cancer using multiple criteria. Results The Prostate Health Index was significantly higher in men with Gleason 7 or greater and “Epstein significant” cancer. On receiver operating characteristic analysis phi had the highest AUC for overall cancer (AUCs phi 0.708, percent free prostate specific antigen 0.648, [-2]proPSA 0.550 and prostate specific antigen 0.516), Gleason 7 or greater (AUCs phi 0.707, percent free prostate specific antigen 0.661, [-2]proPSA 0.558, prostate specific antigen 0.551) and significant cancer (AUCs phi 0.698, percent free prostate specific antigen 0.654, [-2]proPSA 0.550, prostate specific antigen 0.549). At the 90% sensitivity cut point for phi (a score less than 28.6) 30.1% of patients could have been spared an unnecessary biopsy for benign disease or insignificant prostate cancer compared to 21.7% using percent free prostate specific antigen. Conclusions The new phi test outperforms its individual components of total, free and [-2]proPSA for the identification of clinically significant prostate cancer. Phi may be useful as part of a multivariable approach to reduce prostate biopsies and over diagnosis. PMID:25463993

  2. Molecular Epidemiology Investigation of Obesity and Lethal Prostate Cancer

    DTIC Science & Technology

    2015-09-01

    acetylation, DNA methylation  Test experimentally using diet-induced obesity mouse model of prostate cancer (David Labbé and Miles Brown, Dana-Farber...epigenetic state of prostate cancers. Epigenetic alterations, including DNA methylation and histone modifications, are a common feature of cancer and are...transcription of genes involved in cancer-related cellular processes, such as proliferation, apoptosis, inflammation, and invasion (10). Both global DNA

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

    PubMed

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

    2017-04-05

    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.

  4. Linking obesogenic dysregulation to prostate cancer progression

    PubMed Central

    Taylor, Renea A; Lo, Jennifer; Ascui, Natasha; Watt, Matthew J

    2015-01-01

    The global epidemic of obesity is closely linked to the development of serious co-morbidities, including many forms of cancer. Epidemiological evidence consistently shows that obesity is associated with a similar or mildly increased incidence of prostate cancer but, more prominently, an increased risk for aggressive prostate cancer and prostate cancer-specific mortality. Studies in mice demonstrate that obesity induced by high-fat feeding increases prostate cancer progression; however, the mechanisms underpinning this relationship remain incompletely understood. Adipose tissue expansion in obesity leads to local tissue dysfunction and is associated with low-grade inflammation, alterations in endocrine function and changes in lipolysis that result in increased delivery of fatty acids to tissues of the body. The human prostate gland is covered anteriorly by the prominent peri-prostatic adipose tissue and laterally by smaller adipose tissue depots that lie directly adjacent to the prostatic surface. We discuss how the close association between dysfunctional adipose tissue and prostate epithelial cells might result in bi-directional communication to cause increased prostate cancer aggressiveness and progression. However, the literature indicates that several ‘mainstream’ hypotheses regarding obesity-related drivers of prostate cancer progression are not yet supported by a solid evidence base and, in particular, are not supported by experiments using human tissue. Understanding the links between obesity and prostate cancer will have major implications for the health policy for men with prostate cancer and the development of new therapeutic or preventative strategies. PMID:26581226

  5. Prostate cancer immunotherapy: beyond immunity to curability.

    PubMed

    Simons, Jonathan W

    2014-11-01

    Metastatic prostate cancer is the second leading cause of death from cancer in the United States. It is the first prevalent cancer in which overall survival in advanced disease is modestly, but objectively, improved with outpatient delivered dendritic cell-based immunotherapy. More prostate cancer patients have enrolled through Facebook and trusted-site Internet searches in clinical trials for prostate cancer vaccine-based immunotherapy than in immunotherapy trials for lung, breast, colon, pancreas, ovarian, and bladder cancer combined in the past 7 years. Exceptional responses to anti-CTLA-4 treatment have been documented in clinics, and prostate cancer neoantigen characterization and T-cell clonotyping are in their research ascendancy. The prostate is an accessory organ; it is not required for fertility, erectile function, or urinary continence. The true evolutionary advantage of having a prostate for male mammalian physiology is a topic of speculation in seminar rooms and on bar stools, but it remains unknown. Hundreds of prostate lineage-unique proteins (PLUP) exist among the >37,000 normal human prostate lineage-unique open reading frames that can be targeted for immunologic ablation of PLUP(+) prostate cancer cells by prostate-specific autoimmunity. This bioengineered graft-versus-prostate disease is a powerful strategy that can eliminate deaths from prostate cancer. Immunologic tolerance to prostate cancer can be overcome at every clinical stage of presentation. This Cancer Immunology at the Crossroads article aims to present advances in the past two decades of basic, translational, and clinical research in prostate cancer, including bioengineering B-cell and T-cell responses, and ongoing prostate cancer immunotherapy trials.

  6. Serum sialic acid and prostate-specific antigen in differential diagnosis of benign prostate hyperplasia and prostate cancer.

    PubMed

    Romppanen, Jarkko; Haapalainen, Terhi; Punnonen, Kari; Penttilä, Ilkka

    2002-01-01

    In order to improve the diagnostic accuracy of the serum total and free prostate-specific antigen (PSA) in differential diagnosis between benign prostate hyperplasia (BPH) and prostate cancer, the serum total sialic acid (TSA) was measured and logistic regression (LR) models were built. Significantly higher serum PSA (p<0.001) concentrations were observed in patients with prostate cancer compared to control subjects, but no statistically significant differences were found in serum TSA concentrations between these groups. Serum PSA reliably discriminated patients with prostate cancer from control subjects, the area under the ROC curve (AUC) being 0.991 (0.010). When serum PSA was in the gray zone, from 4 to 10 microg/l, the diagnostic accuracy of PSA in discriminating patients with prostate cancer from BPH patients was very poor, AUC being 0.563 (0.132). However, using the same set of patients the LR model combining serum PSA, free to total PSA ratio and TSA values, as well as digital rectal examination results, had good diagnostic accuracy in discriminating the prostate cancer patients from patients with BPH, the area under the ROC curve being 0.895 (0.054). The present data suggest that the logistic regression model combining laboratory measurements and results of the clinical examination may be a useful adjunct in the differential diagnosis of benign and malignant prostate disease.

  7. The G gamma / T-15 transgenic mouse model of androgen-independent prostate cancer: target cells of carcinogenesis and the effect of the vitamin D analogue EB 1089.

    PubMed

    Perez-Stable, Carlos M; Schwartz, Gary G; Farinas, Adan; Finegold, Milton; Binderup, Lise; Howard, Guy A; Roos, Bernard A

    2002-06-01

    Transgenic mouse models of prostate cancer provide unique opportunities to understand the molecular events in prostate carcinogenesis and for the preclinical testing of new therapies. We studied the G gamma T-15 transgenic mouse line, which contains the human fetal globin promoter linked to SV40 T antigen (Tag) and which develops androgen-independent prostate cancer. Using the immunohistochemistry of normal mouse prostates before tumor formation, we showed that the target cells of carcinogenesis in G gamma T-15 mice are located in the basal epithelial layer. We tested the efficacy of the 1,25(OH)(2)D(3) analogue, EB 1089, to chemoprevent prostate cancer in these transgenic mice. Compared with treatment with placebo, treatment with EB 1089 at three different time points before the onset of prostate tumors in mice did not prevent or delay tumor onset. However, EB 1089 significantly inhibited prostate tumor growth. At the highest dose, EB 1089 inhibited prostate tumor growth by 60% (P = 0.0003) and the growth in the number of metastases, although this dose also caused significant hypercalcemia and weight loss. We conducted several in vitro experiments to explore why EB 1089 did not prevent the occurrence of the primary tumors. EB 1089 significantly inhibited the growth of a Tag-expressing human prostate epithelial cell line, BPH-1, and an androgen-insensitive subline of LNCaP cells [which was not inhibited by 1,25(OH)(2)D(3)]. Thus, neither Tag expression nor androgen insensitivity explain the absence of chemopreventive effect. Conversely, neither 1,25(OH)(2)D(3) nor EB 1089 inhibited the growth of the normal rat prostate basal epithelial cell line NRP-152. It is likely that EB 1089 was not effective in delaying the growth of the primary tumor in G gamma T-15 transgenic mice because the target cells of carcinogenesis in these mice are located in the basal epithelial layer. We conclude that G gamma T-15 transgenic mice are a useful model for testing vitamin D

  8. Hormonal therapy of prostate cancer.

    PubMed

    Labrie, Fernand

    2010-01-01

    Of all cancers, prostate cancer is the most sensitive to hormones: it is thus very important to take advantage of this unique property and to always use optimal androgen blockade when hormone therapy is the appropriate treatment. A fundamental observation is that the serum testosterone concentration only reflects the amount of testosterone of testicular origin which is released in the blood from which it reaches all tissues. Recent data show, however, that an approximately equal amount of testosterone is made from dehydroepiandrosterone (DHEA) directly in the peripheral tissues, including the prostate, and does not appear in the blood. Consequently, after castration, the 95-97% fall in serum testosterone does not reflect the 40-50% testosterone (testo) and dihydrotestosterone (DHT) made locally in the prostate from DHEA of adrenal origin. In fact, while elimination of testicular androgens by castration alone has never been shown to prolong life in metastatic prostate cancer, combination of castration (surgical or medical with a gonadotropin-releasing hormone (GnRH) agonist) with a pure anti-androgen has been the first treatment shown to prolong life. Most importantly, when applied at the localized stage, the same combined androgen blockade (CAB) can provide long-term control or cure of the disease in more than 90% of cases. Obviously, since prostate cancer usually grows and metastasizes without signs or symptoms, screening with prostate-specific antigen (PSA) is absolutely needed to diagnose prostate cancer at an 'early' stage before metastasis occurs and the cancer becomes non-curable. While the role of androgens was believed to have become non-significant in cancer progressing under any form of androgen blockade, recent data have shown increased expression of the androgen receptor (AR) in treatment-resistant disease with a benefit of further androgen blockade. Since the available anti-androgens have low affinity for AR and cannot block androgen action completely

  9. The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model

    PubMed Central

    Yoshikawa, Yuki; Takai, Tomoaki; Ibuki, Naokazu; Hirano, Hajime; Nomi, Hayahito; Kawabata, Shinji; Kiyama, Satoshi; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko; Suzuki, Minoru; Kirihata, Mitsunori; Azuma, Haruhito

    2015-01-01

    Purpose Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed. Materials and Methods Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA); Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC) studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment. Results The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean±SD 6.9±1.5 vs 12.7±4.0, p<0.05), while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment. Conclusions This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa. PMID:26325195

  10. The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model.

    PubMed

    Takahara, Kiyoshi; Inamoto, Teruo; Minami, Koichiro; Yoshikawa, Yuki; Takai, Tomoaki; Ibuki, Naokazu; Hirano, Hajime; Nomi, Hayahito; Kawabata, Shinji; Kiyama, Satoshi; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko; Suzuki, Minoru; Kirihata, Mitsunori; Azuma, Haruhito

    2015-01-01

    Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed. Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA); Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC) studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment. The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean ± SD 6.9 ± 1.5 vs 12.7 ± 4.0, p<0.05), while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment. This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa.

  11. Stromal Androgen Receptor Roles in the Development of Normal Prostate, Benign Prostate Hyperplasia, and Prostate Cancer

    PubMed Central

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

    2016-01-01

    The prostate is an androgen-sensitive organ that needs proper androgen/androgen receptor (AR) signals for normal development. The progression of prostate diseases, including benign prostate hyperplasia (BPH) and prostate cancer (PCa), also needs proper androgen/AR signals. Tissue recombination studies report that stromal, but not epithelial, AR plays more critical roles via the mesenchymal-epithelial interactions to influence the early process of prostate development. However, in BPH and PCa, much more attention has been focused on epithelial AR roles. However, accumulating evidence indicates that stromal AR is also irreplaceable and plays critical roles in prostate disease progression. Herein, we summarize the roles of stromal AR in the development of normal prostate, BPH, and PCa, with evidence from the recent results of in vitro cell line studies, tissue recombination experiments, and AR knockout animal models. Current evidence suggests that stromal AR may play positive roles to promote BPH and PCa progression, and targeting stromal AR selectively with AR degradation enhancer, ASC-J9, may allow development of better therapies with fewer adverse effects to battle BPH and PCa. PMID:25432062

  12. Prostate cancer specific survival in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial

    PubMed Central

    Pinsky, Paul F.; Black, Amanda; Parnes, Howard L.; Grubb, Robert; Crawford, E. David; Miller, Anthony; Reding, Douglas; Andriole, Gerald

    2013-01-01

    Background The prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized screening trial demonstrated no mortality effect of screening. Here we analyze prostate cancer specific survival in PLCO and its relation to screening. Methods 76,693 men aged 55–74 were randomized to usual care (n = 38,350) or intervention (n = 38,343). Intervention arm men received annual prostate-specific antigen (6 years) and digital rectal exam (4 years). Men were followed for cancer diagnosis and mortality through 13 years. Medical record abstractors confirmed prostate cancer diagnoses, stage and grade. Prostate-specific survival in PLCO cases was analyzed using Kaplan–Meier analysis and proportional hazards modeling. We utilized data from the Surveillance, Epidemiology and End Results (SEER) program to compute expected survival in PLCO and compared this to observed. Results There was no significant difference in prostate-specific survival rates between arms; 10 year survival rates were 94.7% (intervention, n = 4250 cases) versus 93.5% (usual care, n = 3815 cases). Within the intervention arm, cases never screened in PLCO had lower 10 year survival rates (82%) than screen detected or interval (following a negative screen) cases, both around 95.5%. The ratio of observed to expected 10 year prostate-specific death (1-survival) rates was 0.59 (95% CI: 0.51–0.68) for all PLCO cases, 0.66 (95% CI: 0.51–0.81) for Gleason 5–7 cases and 1.07 (95% CI: 0.87–1.3) for Gleason 8–10 cases. Conclusion Prostate cancer specific survival in PLCO was comparable across arms and significantly better than expected based on nationwide population data. How much of the better survival is due to a healthy volunteer effect and to lead-time and overdiagnosis biases is not readily determinable. PMID:23000116

  13. 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

  14. Reconstructing the Prostate Cancer Transcriptional Regulatory Network

    DTIC Science & Technology

    2010-09-01

    TITLE: Reconstructing the prostate cancer transcriptional regulatory network PRINCIPAL INVESTIGATOR: Keyan Salari...2009 – 30 Sep 2010 5a. CONTRACT NUMBER W81XWH-09-1-0414 4. TITLE AND SUBTITLE Reconstructing the prostate cancer transcriptional regulatory...to novel diagnostic, prognostic, and therapeutic strategies in the future. The overall objective of this study was to reconstruct the prostate

  15. [CCAFU Recommendations 2013: Prostate cancer].

    PubMed

    Salomon, L; Bastide, C; Beuzeboc, P; Cormier, L; Fromont, G; Hennequin, C; Mongiat-Artus, P; Peyromaure, M; Ploussard, G; Renard-Penna, R; Rozet, F; Azria, D; Coloby, P; Molinié, V; Ravery, V; Rebillard, X; Richaud, P; Villers, A; Soulié, M

    2013-11-01

    The sub Comittee prostate of the CCAFU established guidelines for diagnostic, treatment, evaluation and standart of care of prostate cancer. Guidelines 2010 were updated based on systematic literature search performed by the sub-Comittee in Medline and PubMed databases to evaluate references, levels of evidence and grade of recommandation. Pathological examination of the tissue specimens was defined specifically for Gleason score according to ISP 2005 recommandations. Prostate and pelvis RMN became the reference in terms of radiological exam. Individual and early diagnosis of prostate cancer was defined and role of PSA was precised. Active surveillance became one of the standart of care of low-risk tumors, radical prostatectomy remained one of the options for all risk group tumors, length of hormonotherapy in association with radiotherapy was precised according to the risk group. Side effects of hormonotherapy treament needed specific supervision ; hormonotherapy had no indication in case of non metastatic tumors and intermittent hormonotherapy in metastatic tumors. New hormonal drugs in pre and post chemotherapy and bone target drugs opened new therapeutics pathways. From 2010 to 2013, standarts of care of prostate cancer were modified because of results of prospective studies and new therapeutics. They allowed precise treatments for each specific clinical situation. In the future, multidisciplinary treatments for high risk tumors, time of adjuvant treatment and sequencies of new hormonal treatment had to be defined. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  16. Prostate Cancer Chemoprevention Targeting Men with High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) and Atypical Small Acinar Proliferation (ASAP): Model for Trial Design and Outcome Measures

    PubMed Central

    Kumar, Nagi; Crocker, Theresa; Smith, Tiffany; Connors, Shahnjayla; Pow-Sang, Julio; Spiess, Philippe E.; Egan, Kathleen; Quinn, Gwen; Schell, Michael; Sebti, Said; Kazi, Aslam; Chuang, Tian; Salup, Raoul; Helal, Mohamed; Zagaja, Gregory; Trabulsi, Edouard; McLarty, Jerry; Fazili, Tajammul; Williams, Christopher R.; Schreiber, Fred; Anderson, Kyle

    2014-01-01

    In spite of the large number of nutrient-derived agents demonstrating promise as potential chemopreventive agents, most have failed to prove effectiveness in clinical trials. Critical requirements for moving nutrient-derived agents to recommendation for clinical use include adopting a systematic, molecular-mechanism based approach and utilizing the same ethical and rigorous methods such as are used to evaluate other pharmacological agents. Preliminary data on a mechanistic rationale for chemoprevention activity as observed from epidemiological, in vitro and preclinical studies, phase I data of safety in suitable cohorts, duration of intervention based on time to progression of preneoplastic disease to cancer and the use of a valid panel of biomarkers representing the hypothesized carcinogenesis pathway for measuring efficacy must inform the design of phase II clinical trials. The goal of this paper is to provide a model for evaluating a well characterized agent- Polyphenon E- in a phase II clinical trial of prostate cancer chemoprevention. PMID:24533253

  17. Circulating 25-hydroxyvitamin D and prostate cancer survival

    PubMed Central

    Mondul, Alison M.; Weinstein, Stephanie J.; Moy, Kristin A.; Männistö, Satu; Albanes, Demetrius

    2016-01-01

    Background Recent epidemiologic evidence suggests that higher circulating vitamin D does not protect against prostate cancer and, in fact, may increase the risk of developing this malignancy. However, few studies have examined the most clinically relevant outcome, prostate cancer mortality. Methods We examined pre-diagnostic serum 25-hydroxy-vitamin D (25(OH)D) and prostate cancer survival in a cohort of 1,000 cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. During 23 years of follow-up, 363 men died from their disease. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% CI of death from prostate cancer by season-specific quintile of 25(OH)D. Multivariable models were adjusted for age, physical activity, cigarettes per day, and family history of prostate cancer. Results Men with higher serum 25(OH)D were less likely to die from their prostate cancer (Q5 vs. Q1 HR=0.72, 95% CI=0.52 – 0.99, p-trend=0.006). This finding was independent of stage or grade at diagnosis, and appeared restricted to men who survived longer (survived <3.3 years: Q5 vs. Q1 HR=0.95, 95% CI=0.61 – 1.50, p-trend=0.53; survived ≥3.3 years: Q5 vs. Q1 HR=0.53, 95% CI=0.34 – 0.85, p-trend=0.0002). Conclusions In this population of men diagnosed with prostate cancer, higher serum 25(OH)D years prior to diagnosis was associated with longer prostate cancer survival. Impact In light of inconsistent evidence regarding the role of vitamin D in the development of prostate cancer, the present findings regarding the most clinically relevant prostate cancer outcome, disease-specific mortality, could have important public health implications. PMID:26809275

  18. The epidemiology of prostate cancer.

    PubMed

    Boyle, Peter; Severi, Gianluca; Giles, Graham G

    2003-05-01

    The etiology of prostate cancer remains virtually unknown. Although there are a number of new leads with regard to risk factors for prostate cancer, more research is required to confirm them. There is little purpose in conducting further case-control studies of prostate cancer-particularly since the use of PSA testing has become wide-spread. Instead, future epidemiologic studies should focus on prostate tumor subclassification, in terms of method of detection, markers of biological "aggressiveness," and genetic changes. Many of these new leads involve the possible influence of polymorphisms in key genes involved in important physiologic processes in the prostate. To fully explore the complexity of interrelationships between the several elements in these pathways will require large cohort studies in which blood is sampled prior to diagnosis. Such studies will be important for identifying which modifiable aspects of lifestyle (such as diet, alcohol, tobacco, physical activity) might be targeted for intervention, to reduce risk. The detection of early prostate cancers by PSA testing relatives of men with prostate cancer has affected the prevalence of phenocopies and, hence, the meaningfulness of risk estimation in prostate cancer families. Because multiple-case families form the substrate for gene hunting via linkage analysis, this phenocopy phenomenon is going to cause considerable confusion and wasted effort. Presently, men with a family history of prostate cancer can be provided with little advice in terms of preventive action. It is likely that one or more genetic mutations associated with a high risk for prostate cancer will be identified in the near future. Even so, the risks probably will be similar to those for mutations in the first two breast cancer genes--informative for very few families. It is difficult to foresee, as and when high-risk mutation carriers are identified, what advice should be offered to them: prophylactic prostatectomies seem to have less

  19. Stages of Prostate Cancer

    MedlinePlus

    ... tissues to make echoes that form a sonogram (computer picture) of the prostate. Transrectal magnetic resonance imaging ( ... uses a strong magnet, radio waves , and a computer to make a series of detailed pictures of ...

  20. 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.

  1. Differentiation of Neonatal Human-Induced Pluripotent Stem Cells to Prostate Epithelial Cells: A Model to Study Prostate Cancer Development

    DTIC Science & Technology

    2013-06-01

    VM either in vitro or in an in vivo mouse model, include: isoxanthohumol, endostar, zoledronic acid, curcumin , and a group of cell- permeable...mimicry by curcumin through down-regulation of the EphA2/PI3K/ MMP pathway in a murine choroidal melano- ma model. Cancer Biol Ther 2011; 11: 229- 235. [79

  2. Inorganic Arsenic–Related Changes in the Stromal Tumor Microenvironment in a Prostate Cancer Cell–Conditioned Media Model

    PubMed Central

    Shearer, Joseph J.; Wold, Eric A.; Umbaugh, Charles S.; Lichti, Cheryl F.; Nilsson, Carol L.; Figueiredo, Marxa L.

    2015-01-01

    , Figueiredo ML. 2016. Inorganic arsenic–related changes in the stromal tumor microenvironment in a prostate cancer cell–conditioned media model. Environ Health Perspect 124:1009–1015; http://dx.doi.org/10.1289/ehp.1510090 PMID:26588813

  3. 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

  4. Immunotherapy of prostate cancer in a murine model using a novel GnRH based vaccine candidate.

    PubMed

    Junco, Jesús A; Peschke, Peter; Zuna, Ivan; Ehemann, Volker; Fuentes, Franklin; Bover, Eddy; Pimentel, Eulogio; Basulto, Roberto; Reyes, Osvaldo; Calzada, Lesvia; Castro, María D; Arteaga, Niurka; López, Yovisleidis; Garay, Hilda; Hernández, Héctor; Bringas, Ricardo; Guillén, Gerardo E

    2007-12-05

    Previous studies with gonadotrophin releasing hormone (GnRH/LHRH) vaccines have shown the usefulness of immunization against this hormone in prostate cancer. To this end, we have generated a completely synthetic peptide modified at position 6 and attached to the 830-844 tetanic toxoid (TT) helper T cell sequence. Through this work we have demonstrated that the GnRHm1-TT molecule was highly immunogenic when it is formulated as an oil-based emulsion adjuvated with Montanide ISA 51. That results correlated directly with testosterone reduction and tumor growth inhibition of the Dunning R3327-H androgen responsive prostate tumor model in rats. GnRHm1-TT, proved to be safe and useful for future clinical trials.

  5. Copper signaling axis as a target for prostate cancer therapeutics.

    PubMed

    Safi, Rachid; Nelson, Erik R; Chitneni, Satish K; Franz, Katherine J; George, Daniel J; Zalutsky, Michael R; McDonnell, Donald P

    2014-10-15

    Previously published reports indicate that serum copper levels are elevated in patients with prostate cancer and that increased copper uptake can be used as a means to image prostate tumors. It is unclear, however, to what extent copper is required for prostate cancer cell function as we observed only modest effects of chelation strategies on the growth of these cells in vitro. With the goal of exploiting prostate cancer cell proclivity for copper uptake, we developed a "conditional lethal" screen to identify compounds whose cytotoxic actions were manifested in a copper-dependent manner. Emerging from this screen was a series of dithiocarbamates, which, when complexed with copper, induced reactive oxygen species-dependent apoptosis of malignant, but not normal, prostate cells. One of the dithiocarbamates identified, disulfiram (DSF), is an FDA-approved drug that has previously yielded disappointing results in clinical trials in patients with recurrent prostate cancer. Similarly, in our studies, DSF alone had a minimal effect on the growth of prostate cancer tumors when propagated as xenografts. However, when DSF was coadministered with copper, a very dramatic inhibition of tumor growth in models of hormone-sensitive and of castrate-resistant disease was observed. Furthermore, we determined that prostate cancer cells express high levels of CTR1, the primary copper transporter, and additional chaperones that are required to maintain intracellular copper homeostasis. The expression levels of most of these proteins are increased further upon treatment of androgen receptor (AR)-positive prostate cancer cell lines with androgens. Not surprisingly, robust CTR1-dependent uptake of copper into prostate cancer cells was observed, an activity that was accentuated by activation of AR. Given these data linking AR to intracellular copper uptake, we believe that dithiocarbamate/copper complexes are likely to be effective for the treatment of patients with prostate cancer whose

  6. The Thoc1 ribonucleoprotein and prostate cancer progression.

    PubMed

    Chinnam, Meenalakshmi; Wang, Yanqing; Zhang, Xiaojing; Gold, David L; Khoury, Thaer; Nikitin, Alexander Yu; Foster, Barbara A; Li, Yanping; Bshara, Wiam; Morrison, Carl D; Payne Ondracek, Rochelle D; Mohler, James L; Goodrich, David W

    2014-11-01

    The majority of newly diagnosed prostate cancers will remain indolent, but distinguishing between aggressive and indolent disease is imprecise. This has led to the important clinical problem of overtreatment. THOC1 encodes a nuclear ribonucleoprotein whose expression is higher in some cancers than in normal tissue. The hypothesis that THOC1 may be a functionally relevant biomarker that can improve the identification of aggressive prostate cancer has not been tested. THOC1 protein immunostaining was evaluated in a retrospective collection of more than 700 human prostate cancer specimens and the results associated with clinical variables and outcome. Thoc1 was conditionally deleted in an autochthonous mouse model (n = 22 or 23 per genotype) to test whether it is required for prostate cancer progression. All statistical tests were two-sided. THOC1 protein immunostaining increases with higher Gleason score and more advanced Tumor/Node/Metastasis stage. Time to biochemical recurrence is statistically significantly shorter for cancers with high THOC1 protein (log-rank P = .002, and it remains statistically significantly associated with biochemical recurrence after adjusting for Gleason score, clinical stage, and prostate-specific antigen levels (hazard ratio = 1.61, 95% confidence interval = 1.03 to 2.51, P = .04). Thoc1 deletion prevents prostate cancer progression in mice, but has little effect on normal tissue. Prostate cancer cells deprived of Thoc1 show gene expression defects that compromise cell growth. Thoc1 is required to support the unique gene expression requirements of aggressive prostate cancer in mice. In humans, high THOC1 protein immunostaining associates with prostate cancer aggressiveness and recurrence. Thus, THOC1 protein is a functionally relevant molecular marker that may improve the identification of aggressive prostate cancers, potentially reducing overtreatment. © The Author 2014. Published by Oxford University Press. All rights reserved. For

  7. Snus use, smoking and survival among prostate cancer patients.

    PubMed

    Wilson, Kathryn M; Markt, Sarah C; Fang, Fang; Nordenvall, Caroline; Rider, Jennifer R; Ye, Weimin; Adami, Hans-Olov; Stattin, Pär; Nyrén, Olof; Mucci, Lorelei A

    2016-12-15

    Smoking is associated with prostate cancer mortality. The Scandinavian smokeless tobacco product snus is a source of nicotine but not the combustion products of smoke and has not been studied with respect to prostate cancer survival. The study is nested among 9,582 men with incident prostate cancer within a prospective cohort of 336,381 Swedish construction workers. Information on tobacco use was collected at study entry between 1971 and 1992, and categorized into (i) never users of any tobacco, (ii) exclusive snus: ever users of snus only, (iii) exclusive smokers: ever smokers (cigarette, cigar and/or pipe) only and (iv) ever users of both snus and smoking. Hazard ratios for prostate cancer-specific and total mortality for smoking and snus use based on Cox proportional hazards models adjusted for age, calendar period at diagnosis and body mass index at baseline. During 36 years of follow-up, 4,758 patients died-2,489 due to prostate cancer. Compared to never users of tobacco, exclusive smokers were at increased risk of prostate cancer mortality (HR 1.15, 95% CI: 1.05-1.27) and total mortality (HR 1.17, 95% CI: 1.09-1.26). Exclusive snus users also had increased risks for prostate cancer mortality (HR 1.24, 95% CI: 1.03-1.49) and total mortality (HR 1.19, 95% CI: 1.04-1.37). Among men diagnosed with nonmetastatic disease, the HR for prostate cancer death among exclusive snus users was 3.17 (95% CI: 1.66-6.06). The study is limited by a single assessment of tobacco use prior to diagnosis. Snus use was associated with increased risks of prostate cancer and total mortality among prostate cancer patients. This suggests that tobacco-related components such as nicotine or tobacco-specific carcinogens may promote cancer progression independent of tobacco's combustion products. © 2016 UICC.

  8. Linkage and microarray analyses of susceptibility genes in ACI/Seg rats: a model for prostate cancers in the aged.

    PubMed

    Yamashita, Satoshi; Suzuki, Shugo; Nomoto, Tomoko; Kondo, Yasushi; Wakazono, Kuniko; Tsujino, Yoshimi; Sugimura, Takashi; Shirai, Tomoyuki; Homma, Yukio; Ushijima, Toshikazu

    2005-04-01

    ACI/Seg (ACI) rats develop prostate cancers spontaneously with aging, similar to humans. Here, to identify genes involved in prostate cancer susceptibility, we did linkage analysis and oligonucleotide microarray analysis. Linkage analysis was done using 118 effective rats, and prostate cancer susceptibility 1 (Pcs1), whose ACI allele dominantly induced prostate cancers, was mapped on chromosome 19 [logarithm of odds (LOD) score of 5.0]. PC resistance 1 (Pcr1), whose ACI allele dominantly and paradoxically suppressed the size of prostate cancers, was mapped on chromosome 2 (LOD score of 5.0). When linkage analysis was done in 51 rats with single or no macroscopic testicular tumors, which had larger prostates and higher testosterone levels than those with bilateral testicular tumors, Pcs2 and Pcr2 were mapped on chromosomes 20 and 1, respectively. By oligonucleotide microarray analysis with 8,800 probe sets and confirmation by quantitative reverse transcription-PCR, only two genes within these four loci were found to be differentially expressed >1.8-fold. Membrane metalloendopeptidase (Mme), known to inhibit androgen-independent growth of prostate cancers, on Pcr1 was expressed 2.0- to 5.5-fold higher in the ACI prostate, in accordance with its paradoxical effect. Cdkn1a on Pcs2 was expressed 1.5- to 4.5-fold lower in the ACI prostate. Additionally, genes responsible for testicular tumors and unilateral renal agenesis were mapped on chromosomes 11 and 14, respectively. These results showed that prostate cancer susceptibility of ACI rats involves at least four loci, and suggested Mme and Cdkn1a as candidates for Pcr1 and Pcs2.

  9. Prostate cancer postoperative nomogram scores and obesity.

    PubMed

    Major, Jacqueline M; Klonoff-Cohen, Hillary S; Pierce, John P; Slymen, Donald J; Saltzstein, Sidney L; Macera, Caroline A; Mercola, Dan; Kattan, Michael W

    2011-02-24

    Nomograms are tools used in clinical practice to predict cancer outcomes and to help make decisions regarding management of disease. Since its conception, utility of the prostate cancer nomogram has more than tripled. Limited information is available on the relation between the nomograms' predicted probabilities and obesity. The purpose of this study was to examine whether the predictions from a validated postoperative prostate cancer nomogram were associated with obesity. We carried out a cross-sectional analysis of 1220 patients who underwent radical prostatectomy (RP) in southern California from 2000 to 2008. Progression-free probabilities (PFPs) were ascertained from the 10-year Kattan postoperative nomogram. Multivariable logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs). In the present study, aggressive prostate cancer (Gleason ≥7), but not advanced stage, was associated with obesity (p = 0.01). After adjusting for age, black race, family history of prostate cancer and current smoking, an inverse association was observed for 10-year progression-free predictions (OR = 0.50; 95% CI = 0.28-0.90) and positive associations were observed for preoperative PSA levels (OR = 1.23; 95% CI = 1.01-1.50) and Gleason >7 (OR = 1.45; 95% CI = 1.11-1.90). Obese RP patients were more likely to have lower PFP values than non-obese patients, suggesting a higher risk of experiencing prostate cancer progression. Identifying men with potentially higher risks due to obesity may improve disease prognosis and treatment decision-making.

  10. Vaccine Immunotherapy for Prostate Cancer

    DTIC Science & Technology

    2010-05-01

    Center IRB, and the I owa City VA Medical Center Research and Development Committee. During the second and t hird years we have been recruiting pa...American Urologic Association (AUA). (3) Talks to prostate cancer survivor support groups in at the University of I owa , Mercy Medical Center in Cedar

  11. Methylselenium and Prostate Cancer Apoptosis

    DTIC Science & Technology

    2008-02-01

    methylselenol , prostate cancer chemoprevention, apoptosis 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF...considered an immediate precursor to the in vivo active anticancer selenium metabolite methylselenol , greatly sensitized HRPCa cells to undergo

  12. Particle radiotherapy for prostate cancer.

    PubMed

    Shioyama, Yoshiyuki; Tsuji, Hiroshi; Suefuji, Hiroaki; Sinoto, Makoto; Matsunobu, Akira; Toyama, Shingo; Nakamura, Katsumasa; Kudo, Sho

    2015-01-01

    Recent advances in external beam radiotherapy have allowed us to deliver higher doses to the tumors while decreasing doses to the surrounding tissues. Dose escalation using high-precision radiotherapy has improved the treatment outcomes of prostate cancer. Intensity-modulated radiation therapy has been widely used throughout the world as the most advanced form of photon radiotherapy. In contrast, particle radiotherapy has also been under development, and has been used as an effective and non-invasive radiation modality for prostate and other cancers. Among the particles used in such treatments, protons and carbon ions have the physical advantage that the dose can be focused on the tumor with only minimal exposure of the surrounding normal tissues. Furthermore, carbon ions also have radiobiological advantages that include higher killing effects on intrinsic radio-resistant tumors, hypoxic tumor cells and tumor cells in the G0 or S phase. However, the degree of clinical benefit derived from these theoretical advantages in the treatment of prostate cancer has not been adequately determined. The present article reviews the available literature on the use of particle radiotherapy for prostate cancer as well as the literature on the physical and radiobiological properties of this treatment, and discusses the role and the relative merits of particle radiotherapy compared with current photon-based radiotherapy, with a focus on proton beam therapy and carbon ion radiotherapy.

  13. Effect of intermittent fasting on prostate cancer tumor growth in a mouse model.

    PubMed

    Thomas, J A; Antonelli, J A; Lloyd, J C; Masko, E M; Poulton, S H; Phillips, T E; Pollak, M; Freedland, S J

    2010-12-01

    Caloric restriction (CR) has been shown to have anti-cancer properties. However, CR may be difficult to apply in humans secondary to compliance and potentially deleterious effects. An alternative is intermittent CR, or in the extreme case intermittent fasting (IF). In a previous small pilot study, we found 2 days per week of IF with ad libitum feeding on the other days resulted in trends toward prolonged survival of mice bearing prostate cancer xenografts. We sought to confirm these findings in a larger study. A total of 100 (7- to 8-week-old) male severe combined immunodeficiency mice were injected subcutaneously with 1 × 10(5) LAPC-4 prostate cancer cells. Mice were randomized to either ad libitum Western Diet (44% carbohydrates, 40% fat and 16% protein) or ad libitum Western Diet with twice-weekly 24 h fasts (IF). Tumor volumes and mouse bodyweights were measured twice weekly. Mice were killed when tumor volumes reached 1000 mm(3). Serum and tumor were collected for analysis of the insulin/insulin-like growth factor 1 (IGF-1) hormonal axis. Overall, there was no difference in mouse survival (P=0.37) or tumor volumes (P ≥ 0.10) between groups. Mouse body weights were similar between arms (P=0.84). IF mice had significantly higher serum IGF-1 levels and IGF-1/IGFBP-3 ratios at killing (P<0.001). However, no difference was observed in serum insulin, IGFBP-3 or tumor phospho-Akt levels (P ≥ 0.39). IF did not improve mouse survival nor did it delay prostate tumor growth. This may be secondary to metabolic adaptations to the 24 h fasting periods. Future studies are required to optimize CR for application in humans.

  14. Boron intake and prostate cancer risk.

    PubMed

    Gonzalez, Alejandro; Peters, Ulrike; Lampe, Johanna W; White, Emily

    2007-12-01

    Experimental studies suggest that boron may prevent prostate cancer. Only one small epidemiological study has been conducted of boron, which found that those in the highest quartile of boron intake had less than half the risk of prostate cancer versus those in the lowest quartile. We evaluated the association between boron intake and prostate cancer within the VITamins And Lifestyle (VITAL) cohort. A total of 35,244 men completed the baseline supplement and food frequency questionnaire (FFQ) in 2000-2002. A boron database was constructed from published sources to estimate boron intake from the FFQ and from multivitamins. A total of 832 men developed prostate cancer from baseline to 31 December 2004. Dietary boron intake and total boron intake from diet plus multivitamins were not associated with prostate cancer risk. The hazard ratio of prostate cancer for those in the highest versus lowest quartile of total boron intake was 1.17 (95% CI 0.85, 1.61). This risk did not vary by prostate cancer stage or Gleason score. Furthermore, none of the foods high in boron content was associated with a decreased risk of prostate cancer. This cohort study provides no evidence for a preventive role of boron intake on prostate cancer. Since few studies exist on this topic, future research is needed to better elucidate any role that boron may play in the prevention of prostate cancer.

  15. Prostate Cancer Research Training Program

    DTIC Science & Technology

    2014-04-01

    Oncology Departments at the University of Iowa and other institutions. A major project in the lab is targeted therapy of prostate cancer using PSMA...develop novel, immune-based therapies for advanced solid tumors, using the knowledge we gain from our pre-clinical studies. Because her goal is to...in the molecular design, organic synthesis, characterization, and radiolabeling of peptides and small molecules for small molecule cancer therapy

  16. Targeting prostate cancer stem cells.

    PubMed

    Crea, Francesco; Mathews, Lesley A; Farrar, William L; Hurt, Elaine M

    2009-12-01

    Cancer stem cells are the sub-population of cells present within tumors responsible for tumorigenesis. These cells have unique biological properties including self-renewal and the ability to differentiate. Furthermore, it is thought that these cells are more resistant to conventional chemotherapy and, as a result, are responsible for patient relapse. We will discuss the identification of prostate cancer stem cells, their unique properties and how these cells may be targeted for more efficacious therapies.

  17. Early Detection of Prostate Cancer

    DTIC Science & Technology

    2007-01-01

    effective marker for diagnosis and detection of prostate cancer. Low concentrations of PSA would be detected using acoustic wave sensors because of...associated electrical field. For biological sensors, binding of a substance onto the resonating membrane surface causes a decrease in the acoustic...of diverse conditions and diseases including those that affect the thyroid, HIV, diabetes , pregnancy, and several types of cancer. In clinical

  18. Progress Against Prostate Cancer | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Prostate Cancer Progress Against Prostate Cancer Past Issues / Winter 2010 Table of Contents Click ... This can narrow the urethra, decreasing urine flow. Prostate cancer is made up of cells the body does ...

  19. Temperature-dependent activation of differential apoptotic pathways during cryoablation in a human prostate cancer model.

    PubMed

    Robilotto, A T; Baust, J M; Van Buskirk, R G; Gage, A A; Baust, J G

    2013-03-01

    Critical to the continual improvement of cryoablation efficacy is deciphering the biochemical responses of cells to low-temperature exposure. The identification of delayed-onset cell death has allowed for the manipulation of cellular responses through the regulation of apoptosis. We hypothesized that in addition to delayed apoptotic events associated with mild subfreezing temperatures (10 to -25 °C), cells exposed to ultra-low temperatures (<-30 °C) may undergo rapid, early-onset apoptosis. Human prostate cancer model and cells (PC-3) were exposed to temperatures of -60, -30 and -15 °C to simulate a cryoablative procedure. Using a combination of flow-cytometry, fluorescent microscopy and western blot analyses, samples were assessed at various times post thaw to identify the presence, levels and the pathways involved in cell death. Exposure to temperatures <-30 °C yielded a significant apoptotic population within 30 min of thawing, peaking at 90 min (~40%), and by 6 h, only necrosis was observed. In samples only reaching temperatures >-30 °C, apoptosis was not noted until 6-24 h post thaw, with the levels of apoptosis reaching ~10% (-15 °C) and ~25% (-30 °C) at 6 h post thaw. Further, it was found that early-onset apoptosis progressed through a membrane-mediated mechanism, whereas delayed apoptosis progressed through a mitochondrial path. These data demonstrate the impact of apoptotic continuum, whereby the more severe cryogenic stress activated the extrinsic, membrane-regulated pathway, whereas less severe freezing activated the intrinsic, mitochondrial-mediated path. The rapid induction and progression of apoptosis at ultra-low temperatures provides an explanation as to why such results have not previously been identified following freezing. Ultimately, an understanding of the events and signaling pathways involved in triggering apoptosis following freezing may provide a path for selective induction of the rapid-onset and delayed programmed cell death

  20. The 20-core prostate biopsy as an initial strategy: impact on the detection of prostatic cancer.

    PubMed

    Jradi, Mohamed Amine; Dridi, Mohamed; Teyeb, Mourad; Mohamed, Mokhtar Ould Sidi; Khiary, Ramzi; Ghozzi, Samir; Ben Rais, Nawfel

    2010-04-01

    To increase the detection rate of prostate cancer in recent years, we examined the increase in the number of cores taken at initial prostate biopsy. We hypothesized that an increasing number of cores may undermine the accuracy of models predicting the presence of prostate cancer at initial biopsy in patients submitted to 20-core initial biopsy. A total of 232 consecutive patients with prostate-specific antigen (PSA) between 4 and 20 ng/mL and/or abnormal digital rectal examination (DRE) underwent 12-core prostate biopsy protocol (group 1) or 20-core prostate biopsy protocol (group 2). The patients were divided into subgroups according to the results of their serum PSA and prostate volume. We evaluated the cancer detection rate overall and in each subgroup. Clinical data were analyzed using chi-square analysis and the unpaired t-test or 1-way ANOVA with significance considered at 0.05. The 2 groups of patients were not significantly different with regard to parameters (age, abnormal DRE and serum PSA), although median prostate volume in group 1 (57.76 +/- 26.94 cc) were slighter greater than in group 2. Cancer detection rate for patients submitted to 20 prostate biopsy was higher than patients submitted to 12 prostate biopsy (35.2% vs. 25%, p = 0.095). Breakdown to PSA level showed a benefit to 20 prostate biopsy for PSA <6 ng/mL (37.1% vs. 12.9%, p = 0.005). Stratifying results by prostate volume, we found that the improvement of cancer detection rate with 20 prostate biopsy was significant in patients with a prostate volume greater than 60 cc (55% in 20 prostate biopsy vs. 11.3% p < 0.05). Morbidity rates were identical in groups 1 and 2 with no statistically significant difference. There appeared to be no greater risk of infection and bleeding with 20 prostate biopsy protocol. The 20-core biopsy protocol was more efficient than the 12-core biopsy protocol, especially in patients with prostate specific antigen <6 ng/mL and prostate volume greater than 60 cc.

  1. A Comprehensive Panel of Three-Dimensional Models for Studies of Prostate Cancer Growth, Invasion and Drug Responses

    PubMed Central

    Härmä, Ville; Virtanen, Johannes; Mäkelä, Rami; Happonen, Antti; Mpindi, John-Patrick; Knuuttila, Matias; Kohonen, Pekka; Lötjönen, Jyrki; Kallioniemi, Olli; Nees, Matthias

    2010-01-01

    Prostate epithelial cells from both normal and cancer tissues, grown in three-dimensional (3D) culture as spheroids, represent promising in vitro models for the study of normal and cancer-relevant patterns of epithelial differentiation. We have developed the most comprehensive panel of miniaturized prostate cell culture models in 3D to date (n = 29), including many non-transformed and most currently available classic prostate cancer (PrCa) cell lines. The purpose of this study was to analyze morphogenetic properties of PrCa models in 3D, to compare phenotypes, gene expression and metabolism between 2D and 3D cultures, and to evaluate their relevance for pre-clinical drug discovery, disease modeling and basic research. Primary and non-transformed prostate epithelial cells, but also several PrCa lines, formed well-differentiated round spheroids. These showed strong cell-cell contacts, epithelial polarization, a hollow lumen and were covered by a complete basal lamina (BL). Most PrCa lines, however, formed large, poorly differentiated spheroids, or aggressively invading structures. In PC-3 and PC-3M cells, well-differentiated spheroids formed, which were then spontaneously transformed into highly invasive cells. These cell lines may have previously undergone an epithelial-to-mesenchymal transition (EMT), which is temporarily suppressed in favor of epithelial maturation by signals from the extracellular matrix (ECM). The induction of lipid and steroid metabolism, epigenetic reprogramming, and ECM remodeling represents a general adaptation to 3D culture, regardless of transformation and phenotype. In contrast, PI3-Kinase, AKT, STAT/interferon and integrin signaling pathways were particularly activated in invasive cells. Specific small molecule inhibitors targeted against PI3-Kinase blocked invasive cell growth more effectively in 3D than in 2D monolayer culture, or the growth of normal cells. Our panel of cell models, spanning a wide spectrum of phenotypic

  2. Metabolic imbalance and prostate cancer progression

    PubMed Central

    Burton, Anya J; Tilling, Kate M; Holly, Jeff M; Hamdy, Freddie C; Rowlands, Mari-Anne E; Donovan, Jenny L; Martin, Richard M

    2010-01-01

    There is substantial evidence implicating environmental factors in the progression of prostate cancer. The metabolic consequences of a western lifestyle, such as obesity, insulin resistance and abnormal hormone production have been linked to prostate carcinogenesis through multiple overlapping pathways. Insulin resistance results in raised levels of the mitogens insulin and insulin-like growth factor-1, both of which may affect prostate cancer directly, or through their effect on other metabolic regulators. Obesity is associated with abnormal levels of adipocyte-derived peptides (adipokines), sex hormones and inflammatory cytokines. Adipokines have been shown to influence prostate cancer in both cell culture studies and observational, population level studies. Testosterone appears to have a complex relationship with prostate carcinogenesis, and it has been suggested that the lower levels associated with obesity may select for more aggressive androgen independent prostate cancer cells. Prostatic inflammation, caused by infection, urinary reflux or dietary toxins, frequently occurs prior to cancer development and may influence progression to advanced disease. High levels of ω-6 fatty acids in the diet may lead to the production of further inflammatory molecules that may influence prostate cancer. Increased fatty acid metabolism occurs within tumour cells, providing a potential target for prostate cancer therapies. Aberrations in amino acid metabolism have also been identified in prostate cancer tissue, particularly in metastatic cancer. This evidence indicates lifestyle interventions may be effective in reducing the incidence of clinical disease. However, much more research is needed before recommendations are made. PMID:21532839

  3. Internal Audit of a Comprehensive IMRT Program for Prostate Cancer: A Model for Centers in Developing Countries?

    SciTech Connect

    Koh, Wee Yao; Ren Wei; Mukherjee, Rahul K.; Chung, Hans T.

    2009-08-01

    Purpose: With improving regional prosperity, significant capital investments have been made to rapidly expand radiotherapy capacity across Southeast Asia. Yet little has been reported on the implementation of adequate quality assurance (QA) in patient management. The objective of this study is to perform an in-depth QA assessment of our definitive intensity-modulated radiotherapy (IMRT) program for prostate cancer since its inception. Methods and Materials: The department's prostate IMRT program was modeled after that of University of California San Francisco. A departmental protocol consisting of radiotherapy volume/dose and hormone sequencing/duration and a set of 18 dose objectives to the target and critical organs were developed, and all plans were presented at the weekly departmental QA rounds. All patients treated with definitive IMRT for nonmetastatic prostate cancer were retrospectively reviewed. Protocol adherence, dosimetry data, toxicities, and outcomes were evaluated. Results: Since 2005, 76 patients received IMRT: 54 with whole-pelvis and 22 with prostate-only treatment. Of the 1,140 recorded dosimetric end points, 39 (3.3%) did not meet the protocol criteria. At QA rounds, no plans required a revision. Only one major protocol violation was observed. Two and two cases of Grade 3-4 acute and late toxicities, respectively, were observed. Five (8.8%) patients developed proctitis, but only one required argon laser therapy. Conclusions: Our comprehensive, practice-adapted QA measures appeared to ensure that we were able to consistently generate conforming IMRT plans with acceptable toxicities. These measures can be easily integrated into other clinics contemplating on developing such a program.

  4. Internal audit of a comprehensive IMRT program for prostate cancer: a model for centers in developing countries?

    PubMed

    Koh, Wee Yao; Ren, Wei; Mukherjee, Rahul K; Chung, Hans T

    2009-08-01

    With improving regional prosperity, significant capital investments have been made to rapidly expand radiotherapy capacity across Southeast Asia. Yet little has been reported on the implementation of adequate quality assurance (QA) in patient management. The objective of this study is to perform an in-depth QA assessment of our definitive intensity-modulated radiotherapy (IMRT) program for prostate cancer since its inception. The department's prostate IMRT program was modeled after that of the University of California San Francisco. A departmental protocol consisting of radiotherapy volume/dose and hormone sequencing/duration and a set of 18 dose objectives to the target and critical organs were developed, and all plans were presented at the weekly departmental QA rounds. All patients treated with definitive IMRT for nonmetastatic prostate cancer were retrospectively reviewed. Protocol adherence, dosimetry data, toxicities, and outcomes were evaluated. Since 2005, 76 patients received IMRT: 54 with whole-pelvis and 22 with prostate-only treatment. Of the 1,140 recorded dosimetric end points, 39 (3.3%) did not meet the protocol criteria. At QA rounds, no plans required a revision. Only one major protocol violation was observed. Two and two cases of Grade 3-4 acute and late toxicities, respectively, were observed. Five (8.8%) patients developed proctitis, but only one required argon laser therapy. Our comprehensive, practice-adapted QA measures appeared to ensure that we were able to consistently generate conforming IMRT plans with acceptable toxicities. These measures can be easily integrated into other clinics contemplating on developing such a program.

  5. Differential expression and regulation of vitamin D hydroxylases and inflammatory genes in prostate stroma and epithelium by 1,25-dihydroxyvitamin D in men with prostate cancer and an in vitro model.

    PubMed

    Giangreco, Angeline A; Dambal, Shweta; Wagner, Dennis; Van der Kwast, Theodorus; Vieth, Reinhold; Prins, Gail S; Nonn, Larisa

    2015-04-01

    Previous work on vitamin D in the prostate has focused on the prostatic epithelium, from which prostate cancer arises. Prostatic epithelial cells are surrounded by stroma, which has well-established regulatory control over epithelial proliferation, differentiation, and the inflammatory response. Here we examined the regulation of vitamin D-related genes and inflammatory genes by 1α,25-dihydroxyvitamin D3 (1,25(OH)2D) in laser-capture microdissected prostate tissue from a vitamin D3 clinical trial and in an in vitro model that facilitates stromal-epithelial crosstalk. Analysis of the trial tissues showed that VDR was present in both cell types, whereas expression of the hydroxylases was the highest in the epithelium. Examination of gene expression by prostatic (1,25(OH)2D) concentrations showed that VDR was significantly lower in prostate tissues with the highest concentration of 1,25(OH)2D, and down-regulation of VDR by 1,25(OH) 2D was confirmed in the primary cell cultures. Analysis of inflammatory genes in the patient tissues revealed that IL-6 expression was the highest in the prostate stroma while PTGS2 (COX2) levels were lowest in the prostate cancer tissues from men in the highest tertile of prostatic 1,25(OH)2D. In vitro, TNF-α, IL-6 and IL-8 were suppressed by 1,25 (OH)2D in the primary epithelial cells, whereas TNF-α and PTGS2 were suppressed by 1,25(OH) 2D in the stromal cells. Importantly, the ability of 1,25(OH)2D to alter pro-inflammatory-induced changes in epithelial cell growth were dependent on the presence of the stromal cells. In summary, whereas both stromal and epithelial cells of the prostate express VDR and can presumably respond to 1,25(OH)2D, the prostatic epithelium appears to be the main producer of 1,25(OH)2D. Further, while the prostate epithelium was more responsive to the anti-inflammatory activity of 1,25 (OH)2D than stromal cells, stroma-epithelial crosstalk enhanced the phenotypic effects of 1,25(OH)2D and the inflammatory

  6. CD24 Is Not Required for Tumor Initiation and Growth in Murine Breast and Prostate Cancer Models.

    PubMed

    Cremers, Natascha; Neeb, Antje; Uhle, Tanja; Dimmler, Arno; Rothley, Melanie; Allgayer, Heike; Fodde, Riccardo; Sleeman, Jonathan Paul; Thiele, Wilko

    2016-01-01

    CD24 is a small, heavily glycosylated, GPI-linked membrane protein, whose expression has been associated with the tumorigenesis and progression of several types of cancer. Here, we studied the expression of CD24 in tumors of MMTV-PyMT, Apc1572/T+ and TRAMP genetic mouse models that spontaneously develop mammary or prostate carcinoma, respectively. We found that CD24 is expressed during tumor development in all three models. In MMTV-PyMT and Apc1572T/+ breast tumors, CD24 was strongly but heterogeneously expressed during early tumorigenesis, but decreased in more advanced stages, and accordingly was increased in poorly differentiated lesions compared with well differentiated lesions. In prostate tumors developing in TRAMP mice, CD24 expression was strong within hyperplastic lesions in comparison with non-hyperplastic regions, and heterogeneous CD24 expression was maintained in advanced prostate carcinomas. To investigate whether CD24 plays a functional role in tumorigenesis in these models, we crossed CD24 deficient mice with MMTV-PyMT, Apc1572T/+ and TRAMP mice, and assessed the influence of CD24 deficiency on tumor onset and tumor burden. We found that mice negative or positive for CD24 did not significantly differ in terms of tumor initiation and burden in the genetic tumor models tested, with the exception of Apc1572T/+ mice, in which lack of CD24 reduced the mammary tumor burden slightly but significantly. Together, our data suggest that while CD24 is distinctively expressed during the early development of murine mammary and prostate tumors, it is not essential for the formation of tumors developing in MMTV-PyMT, Apc1572T/+ and TRAMP mice.

  7. An informatics model for tissue banks – Lessons learned from the Cooperative Prostate Cancer Tissue Resource

    PubMed Central

    Patel, Ashokkumar A; Gilbertson, John R; Parwani, Anil V; Dhir, Rajiv; Datta, Milton W; Gupta, Rajnish; Berman, Jules J; Melamed, Jonathan; Kajdacsy-Balla, Andre; Orenstein, Jan; Becich, Michael J

    2006-01-01

    Background Advances in molecular biology and growing requirements from biomarker validation studies have generated a need for tissue banks to provide quality-controlled tissue samples with standardized clinical annotation. The NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) is a distributed tissue bank that comprises four academic centers and provides thousands of clinically annotated prostate cancer specimens to researchers. Here we describe the CPCTR information management system architecture, common data element (CDE) development, query interfaces, data curation, and quality control. Methods Data managers review the medical records to collect and continuously update information for the 145 clinical, pathological and inventorial CDEs that the Resource maintains for each case. An Access-based data entry tool provides de-identification and a standard communication mechanism between each group and a central CPCTR database. Standardized automated quality control audits have been implemented. Centrally, an Oracle database has web interfaces allowing multiple user-types, including the general public, to mine de-identified information from all of the sites with three levels of specificity and granularity as well as to request tissues through a formal letter of intent. Results Since July 2003, CPCTR has offered over 6,000 cases (38,000 blocks) of highly characterized prostate cancer biospecimens, including several tissue microarrays (TMA). The Resource developed a website with interfaces for the general public as well as researchers and internal members. These user groups have utilized the web-tools for public query of summary data on the cases that were available, to prepare requests, and to receive tissues. As of December 2005, the Resource received over 130 tissue requests, of which 45 have been reviewed, approved and filled. Additionally, the Resource implemented the TMA Data Exchange Specification in its TMA program and created a computer program for

  8. An informatics model for tissue banks--lessons learned from the Cooperative Prostate Cancer Tissue Resource.

    PubMed

    Patel, Ashokkumar A; Gilbertson, John R; Parwani, Anil V; Dhir, Rajiv; Datta, Milton W; Gupta, Rajnish; Berman, Jules J; Melamed, Jonathan; Kajdacsy-Balla, Andre; Orenstein, Jan; Becich, Michael J

    2006-05-05

    Advances in molecular biology and growing requirements from biomarker validation studies have generated a need for tissue banks to provide quality-controlled tissue samples with standardized clinical annotation. The NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) is a distributed tissue bank that comprises four academic centers and provides thousands of clinically annotated prostate cancer specimens to researchers. Here we describe the CPCTR information management system architecture, common data element (CDE) development, query interfaces, data curation, and quality control. Data managers review the medical records to collect and continuously update information for the 145 clinical, pathological and inventorial CDEs that the Resource maintains for each case. An Access-based data entry tool provides de-identification and a standard communication mechanism between each group and a central CPCTR database. Standardized automated quality control audits have been implemented. Centrally, an Oracle database has web interfaces allowing multiple user-types, including the general public, to mine de-identified information from all of the sites with three levels of specificity and granularity as well as to request tissues through a formal letter of intent. Since July 2003, CPCTR has offered over 6,000 cases (38,000 blocks) of highly characterized prostate cancer biospecimens, including several tissue microarrays (TMA). The Resource developed a website with interfaces for the general public as well as researchers and internal members. These user groups have utilized the web-tools for public query of summary data on the cases that were available, to prepare requests, and to receive tissues. As of December 2005, the Resource received over 130 tissue requests, of which 45 have been reviewed, approved and filled. Additionally, the Resource implemented the TMA Data Exchange Specification in its TMA program and created a computer program for calculating PSA recurrence

  9. Identification of Prostate Cancer-Related Genes Using Inhibition of NMD in Prostate Cancer Cell Lines

    DTIC Science & Technology

    2005-01-01

    TITLE AND SUBTITLE 5. FUNDING NUMBERS Identification of Prostate Cancer -Related Genes Using W81XWH-04- 1 -0045 Inhibition of NMD in Prostate Cancer Cell...analytical filter to the prostate cancer cell lines 22RV- 1 and DU-145. Ten genes for each cell line have been selected for sequencing analysis.(Table...list of candidate genes for sequencing analysis from the LNCaP, PC3, 22RV- 1 and DU- 145 prostate cancer cell lines has been produced REPORTABLE

  10. Isolation of cancer stem cells from human prostate cancer samples.

    PubMed

    Vidal, Samuel J; Quinn, S Aidan; de la Iglesia-Vicente, Janis; Bonal, Dennis M; Rodriguez-Bravo, Veronica; Firpo-Betancourt, Adolfo; Cordon-Cardo, Carlos; Domingo-Domenech, Josep

    2014-03-14

    The cancer stem cell (CSC) model has been considerably revisited over the last two decades. During this time CSCs have been identified and directly isolated from human tissues and serially propagated in immunodeficient mice, typically through antibody labeling of subpopulations of cells and fractionation by flow cytometry. However, the unique clinical features of prostate cancer have considerably limited the study of prostate CSCs from fresh human tumor samples. We recently reported the isolation of prostate CSCs directly from human tissues by virtue of their HLA class I (HLAI)-negative phenotype. Prostate cancer cells are harvested from surgical specimens and mechanically dissociated. A cell suspension is generated and labeled with fluorescently conjugated HLAI and stromal antibodies. Subpopulations of HLAI-negative cells are finally isolated using a flow cytometer. The principal limitation of this protocol is the frequently microscopic and multifocal nature of primary cancer in prostatectomy specimens. Nonetheless, isolated live prostate CSCs are suitable for molecular characterization and functional validation by transplantation in immunodeficient mice.

  11. Granulomatous prostatitis after intravesical immunotherapy mimicking prostate cancer.

    PubMed

    Białek, Waldemar; Rudzki, Sławomir; Iberszer, Paweł; Wronecki, Lech

    2016-12-01

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

  12. Granulomatous prostatitis after intravesical immunotherapy mimicking prostate cancer

    PubMed Central

    Rudzki, Sławomir; Iberszer, Paweł; Wronecki, Lech

    2016-01-01

    Intravesical immunotherapy with attenuated strains of Mycobacterium bovis is a widely used therapeutic option in patients with non-muscle-invasive transitional cell carcinoma of the bladder. A rare complication of intravesical therapy with the Bacillus Calmette-Guérin vaccine is granulomatous prostatitis, which due to increasing levels of prostate-specific antigen and abnormalities found in transrectal examination of the prostate may suggest concomitant prostate cancer. A case of extensive granulomatous prostatitis in a 61-year-old patient which occurred after the first course of a well-tolerated Bacillus Calmette-Guérin therapy is presented. Due to abnormalities found in rectal examination and an abnormal transrectal ultrasound image of the prostate with extensive infiltration mimicking neoplastic hyperplasia a core biopsy of the prostate was performed. Histopathological examination revealed inflammatory infiltration sites of tuberculosis origin. PMID:28138411

  13. Design of Curcumin loaded Cellulose Nanoparticles for Prostate Cancer

    PubMed Central

    Yallapu, Murali Mohan; Dobberpuhl, Mitch Ray; Maher, Diane Michele; Jaggi, Meena; Chauhan, Subhash Chand

    2013-01-01

    Prostate cancer (PC) is the most frequently diagnosed disease in men in the United States. Curcumin (CUR), a natural polyphenol, has shown potent anti-cancer efficacy in various types of cancers. However, suboptimal pharmacokinetics and poor bioavailability limit its effective use in cancer therapeutics. Several successful CUR nanoformulations have recently been reported which improve upon these features; however there is no personalized safe nanoformulation for prostate cancer. This study contributes two important scientific aspects of prostate cancer therapeutics. The first objective was to investigate the comparative cellular uptake and cytotoxicity evaluation of β-cyclodextrin (CD), hydroxyl propyl methyl cellulose (cellulose), poly(lactic-co-glycolic acid) (PLGA), magnetic nanoparticles (MNP), and dendrimer based CUR nanoformulations in prostate cancer cells. Curcumin loaded cellulose nanoparticles (cellulose-CUR) formulation exhibited the highest cellular uptake and caused maximum ultrastructural changes related to apoptosis (presence of vacuoles) in prostate cancer cells. Secondly, the anti-cancer potential of the optimized cellulose-CUR formulation was evaluated in cell culture models using cell proliferation, colony formation and apoptosis (7-AAD staining) assays. In these assays, the cellulose-CUR formulation showed improved anti-cancer efficacy compared to free curcumin. Our study shows, for the first time, the feasibility of cellulose-CUR formulation and its potential use in prostate cancer therapy. PMID:21892919

  14. Estimating the Need for Radiotherapy for Patients With Prostate, Breast, and Lung Cancers: Verification of Model Estimates of Need With Radiotherapy Utilization Data From British Columbia

    SciTech Connect

    Tyldesley, Scott; Delaney, Geoff; Foroudi, Farshad; Barbera, Lisa; Kerba, Marc; Mackillop, William

    2011-04-01

    Purpose: Estimates of the need for radiotherapy (RT) using different methods (criterion based benchmarking [CBB]and the Canadian [C-EBEST]and Australian [A-EBEST]epidemiologically based estimates) exist for various cancer sites. We compared these model estimates to actual RT rates for lung, breast, and prostate cancers in British Columbia (BC). Methods and Materials: All cases of lung, breast, and prostate cancers in BC from 1997 to 2004 and all patients receiving RT within 1 year (RT{sub 1Y}) and within 5 years (RT{sub 5Y}) of diagnosis were identified. The RT{sub 1Y} and RT{sub 5Y} proportions in health regions with a cancer center for the most recent year were then calculated. RT rates were compared with CBB and EBEST estimates of RT needs. Variation was assessed by time and region. Results: The RT{sub 1Y} in regions with a cancer center for lung, breast, and prostate cancers were 51%, 58%, and 33% compared with 45%, 57%, and 32% for C-EBEST and 41%, 61%, and 37% for CBB models. The RT{sub 5Y} rates in regions with a cancer center for lung, breast, and prostate cancers were 59%, 61%, and 40% compared with 61%, 66%, and 61% for C-EBEST and 75%, 83%, and 60% for A-EBEST models. The RT{sub 1Y} rates increased for breast and prostate cancers. Conclusions: C-EBEST and CBB model estimates are closer to the actual RT rates than the A-EBEST estimates. Application of these model estimates by health care decision makers should be undertaken with an understanding of the methods used and the assumptions on which they were based.

  15. Imaging for Prostate Cancer Recurrence.

    PubMed

    Maurer, Tobias; Eiber, Matthias; Fanti, Stefano; Budäus, Lars; Panebianco, Valeria

    2016-06-01

    Correct identification of metastatic sites in recurrent prostate cancer (PCa) is of crucial importance because it leads to further treatment decisions. To provide an overview on current imaging procedures and their performance in recurrent PCa. Medline search via PubMed was performed with the keywords imaging, recurrent, and prostate cancer as well as more detailed searches including the keywords bone scan, bone scintigraphy, computed tomography, magnetic resonance imaging, positron emission tomography, PET, choline, FDG, prostate-specific membrane antigen, and PSMA, with emphasis on recent literature from 2010 to the present. Non-English published literature was excluded. Abstracts and full-text articles were reviewed and assessed for relevant content. In diagnostic imaging and particularly with newer technologies like positron emission tomography (PET), a profound lack of prospectively designed studies in recurrent PCa has to be noted. In most studies histologic validation has only been performed in a subset of patient cohorts. Heterogeneity of included patient cohorts, lack of standardized assessment, as well as diverging end points, hamper systematic comparison of different image modalities. Thus evidence for currently used imaging in recurrent PCa is only presented descriptively. Computed tomography and magnetic resonance imaging (MRI) as well as bone scintigraphy still represent the standard imaging for recurrent PCa; however, particularly for detection of local recurrence, multiparametric MRI is a valuable imaging modality. PET using choline and particularly tracers against prostate-specific membrane antigen might improve visualization of metastatic lesions. These findings need to be validated in prospective trials. Imaging of recurrent prostate cancer (PCa) is important to guide further treatment. Computed tomography, magnetic resonance imaging, and bone scintigraphy represent the current standard. Positron emission tomography, especially with cancer

  16. Magnetic Resonance Spectroscopy (MRS) of Prostatic Fluids for Early Detection of Prostate Cancer

    DTIC Science & Technology

    2005-10-01

    most widely used marker of prostate cancer - and prostate cancer risk. Moreover, benign prostatic hyperplasia (BPH), which is also strongly associated...Vigneron, D.B., Konety, B., Nelson, S.J., Narayan, P., and Hricak, H. Citrate as in vivo marker to discriminate prostate cancer from benign prostatic hyperplasia and

  17. Use of a correlation analysis model in the optimization of intensity-modulated radiotherapy of prostate cancer.

    PubMed

    Li, Xiadong; Deng, Qinghua; Ma, Shenglin; Zhang, K E; Wu, Zhibing; Lai, Jianjun; Tang, Rongjun; Ren, Yao; Wang, Jiahao; Xu, Lixia

    2015-12-01

    The aim of the present study was to develop a statistical model-based method for the optimization of intensity-modulated radiotherapy (IMRT). A prostate cancer IMRT plan was redesigned while retaining the same beam orientation and prescribed dose as the regular plan. A series of dosimetric parameters were generated, and a 4-step protocol was performed to analyze the data: i) The tumor control probability of the target was ensured by setting a number of strict constraint parameters so that much of the target was covered by the 95% isodose line; ii) the parameters for optimization [weight ratio, equivalent characteristic parameter a and maximum equivalent uniform dose of the organ at risk (OAR)] were adjusted; iii) the overall optimization space (OOS) was determined via analysis of the dose-parameter tables based on the correlation factor (CF) and optimization efficiency factor analysis; iv) the OOS in the Pinnacle V7.6 treatment planning system with IMRT function was transposed. A selected optimization phenomenon existed when different optimization methods were used to optimize dose distribution to the targets and OARs, which demonstrates a wide variation in the CFs between the percentage of planning target volume receiving 95% of the prescribed dose and the maximum dose of the bladder, rectum and femur. The OOS used to optimize the randomly selected plan exhibited relatively high efficiency, with benefits for the optimization of IMRT plans. For patients with prostate cancer who require complex IMRT plan optimization, the obtained OOS from the two core analysis techniques is likely to have relatively high efficiency in achieving an optimized plan. These results suggest that the correlation analysis model is a novel method for the optimization of IMRT for prostate cancer.

  18. Combination of Fospeg-IPDT and a natural antioxidant compound prevents photosensitivity in a murine prostate cancer tumour model.

    PubMed

    Petri, Aspasia; Alexandratou, Eleni; Kyriazi, Maria; Rallis, Michail; Roussis, Vassilios; Yova, Dido

    2012-06-01

    The aim of the present research was to investigate the potential use of a natural compound rich in antioxidant agents, derived from Pinus halepensis (P. halepensis), to prevent PDT induced photosensitivity. The present research progressed in two levels. The first one evolved the optimization of Fospeg-interstitial photodynamic therapy (IPDT) in a prostate cancer animal model. In the second one, P. halepensis bark extract, was evaluated for its potential use to prevent photosensitivity. Two sets of experiments were performed, IPDT only and IPDT in the presence of antioxidant. For both of them, Fospeg was administrated intravenously to SCID mice bearing prostate cancer, followed by IPDT after 6 h. For the IPDT+antioxidant experiments, P. halepensis was injected intratumourously 1 h prior the tumour illumination. Treatment outcome was monitored twice a week by an imaging system and by measuring tumour dimensions using a caliper. Photosensitivity was assessed by monitoring erythema of the tail using the imaging system. IPDT with Fospeg and 15 J total light energy is a therapeutic scheme that can eliminate tumours in the murine model of prostate cancer. Two months after complete tumour remission no tumour recurrence was observed. Also, the cosmetic outcome of the research was excellent. The major drawback of this treatment scheme was that 90% of the animals developed photosensitivity. The addition of P. halepensis bark extract resulted in prevention of the photosensitivity, leaving PDT outcome unaffected. The combined use of PDT and the used antioxidant agent could broaden the implementation of photodynamic therapy, by eliminating photosensitivity. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. High-Throughput Detection of Prostate Cancer in Histological Sections Using Probabilistic Pairwise Markov Models

    PubMed Central

    Monaco, James P.; Tomaszewski, John E.; Feldman, Michael D.; Hagemann, Ian; Moradi, Mehdi; Mousavi, Parvin; Boag, Alexander; Davidson, Chris; Abolmaesumi, Purang; Madabhushi, Anant

    2010-01-01

    In this paper we present a high-throughput system for detecting regions of carcinoma of the prostate (CaP) in HSs from radical prostatectomies (RPs) using probabilistic pairwise Markov models (PPMMs), a novel type of Markov random field (MRF). At diagnostic resolution a digitized HS can contain 80K×70K pixels — far too many for current automated Gleason grading algorithms to process. However, grading can be separated into two distinct steps: 1) detecting cancerous regions and 2) then grading these regions. The detection step does not require diagnostic resolution and can be performed much more quickly. Thus, we introduce a CaP detection system capable of analyzing an entire digitized whole-mount HS (2×1.75 cm2) in under three minutes (on a desktop computer) while achieving a CaP detection sensitivity and specificity of 0.87 and 0.90, respectively. We obtain this high-throughput by tailoring the system to analyze the HSs at low resolution (8 µm per pixel). This motivates the following algorithm: Step 1) glands are segmented, Step 2) the segmented glands are classified as malignant or benign, and Step 3) the malignant glands are consolidated into continuous regions. The classification of individual glands leverages two features: gland size and the tendency for proximate glands to share the same class. The latter feature describes a spatial dependency which we model using a Markov prior. Typically, Markov priors are expressed as the product of potential functions. Unfortunately, potential functions are mathematical abstractions, and constructing priors through their selection becomes an ad hoc procedure, resulting in simplistic models such as the Potts. Addressing this problem, we introduce PPMMs which formulate priors in terms of probability density functions, allowing the creation of more sophisticated models. To demonstrate the efficacy of our CaP detection system and assess the advantages of using a PPMM prior instead of the Potts, we alternately incorporate

  20. [Prostate cancer brachytherapy].

    PubMed

    Pommier, P; Guérif, S; Peiffert, D; Créhange, G; Hannoun-Lévi, J-M; de Crevoisier, R

    2016-09-01

    Prostate brachytherapy techniques are described, concerning both Iodine 125 high dose rate brachytherapy. The following parts are presented: brachytherapy indications, technical description, immediate postoperative management and post-treatment evaluation, and 4 to 6 weeks as well as long-term follow-up. Copyright © 2016. Published by Elsevier SAS.

  1. Clarifying the positive association between education and prostate cancer: a Monte Carlo simulation approach.

    PubMed

    Pudrovska, Tetyana; Anishkin, Andriy

    2015-04-01

    Using the 1993-2011 data from the Wisconsin Longitudinal Study (N = 5,218), we examine prostate cancer screening, mortality after the diagnosis, and health behaviors as potential mechanisms explaining the paradoxical association between men's higher education and higher prostate cancer risk. Our study combines within-cohort longitudinal hazard models predicting a prostate cancer diagnosis with Monte Carlo simulations estimating the joint effects of socioeconomic differences in prostate cancer screening and mortality after the diagnosis. Our findings strongly suggest that higher utilization of prostate cancer screening and lower mortality after the diagnosis are important explanations for higher prostate rates among more educated men. In addition to applying an innovative method to the issues of prostate cancer incidence and survival, our results have potentially important implications for the current debate about the utility of prostate cancer screening as well as for accurate predictions of future mortality and morbidity trends in the expanding older population.

  2. CTLA-4 Blockade-Based Immunotherapy in Prostate Cancer

    DTIC Science & Technology

    2006-01-01

    V, Bok R, Small EJ. Prostate-specific antigen kinetics as a measure of the biologic effect of granulocyte- macrophage colony-stimulating factor in...Kwon ED, Truong T, Choi EM, Greenberg NM, et al. Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade

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

    PubMed

    Iversen, Peter; Roder, Martin Andreas

    2008-03-01

    The Early Prostate Cancer program is investigating the addition of bicalutamide 150 mg to standard care for localized or locally advanced, nonmetastatic prostate cancer. The third program analysis, at 7.4 years' median follow-up, has shown that bicalutamide 150 mg does not benefit patients with localized disease, but does confer significant progression-free survival benefits in patients with locally advanced disease, irrespective of standard care received. In patients receiving radiotherapy for locally advanced disease, bicalutamide 150 mg significantly reduced the risk of death by 35%; the magnitude of this benefit compares favorably with that of adjuvant luteinizing hormone-releasing hormone agonist therapy in a similar population. Bicalutamide 150 mg represents an alternative to castration for patients with locally advanced disease who wish to avoid the side effects associated with castration.

  4. Targeting Prostate Cancer with Multifunctional Nanoparticles

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0487 TITLE: Targeting Prostate Cancer with Multifunctional Nanoparticles PRINCIPAL INVESTIGATOR: Darryl Martin...Targeting Prostate Cancer with Multifunctional Nanoparticles 5b. GRANT NUMBER W81XWH-14-1-0487 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Darryl...STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Prostate cancer cells were transfected with claudin siRNA

  5. Prostate Cancer Presenting with Parietal Bone Metastasis

    PubMed Central

    Pare, Abdoul Karim; Abubakar, Babagana Mustapha; Kabore, Moussa

    2017-01-01

    Bone metastases from prostate cancer are very common. They are usually located on the axial skeleton. However, cranial bone metastases especially to the parietal bone are rare. We report a case of metastatic prostate cancer presenting with left parietal bone metastasis in a patient with no urological symptoms or signs. We should consider prostate cancer in any man above 60 years presenting unusual bone lesions.

  6. The Infectious Pathogenesis of Prostate Cancer

    DTIC Science & Technology

    2009-03-01

    al. Plasma antibodies against Trichomonas vaginalis and subsequent risk of prostate cancer. Cancer Epidemiology Biomarkers and Prevention 2006;15...infectious agents with respect to prostate cancer: T vaginalis , the most common non-viral sexually transmitted infection, and the recently identified...To characterize the role of the infectious protozoa T. vaginalis in prostate carcinogenesis and progression. The current study is nested within the

  7. Targeting TMPRSS2 ERG in Prostate Cancer

    DTIC Science & Technology

    2016-09-01

    molecules in prostate cancer cells for perturbations that would modulate the ERG signature. These results will provide new insights into ERG function...prostate cancer, however, the exact role of TMPRSS2-ERG in tumorigenesis is unclear, making it difficult to design assays to target its function...essential for TMPRSS2-ERG activity in prostate cancer cells (months 1-28) 1a. Generate and titer lentiviruses expressing shRNAs targeting

  8. Molecular Imaging of Prostate Cancer: PET Radiotracers

    PubMed Central

    Jadvar, Hossein

    2012-01-01

    OBJECTIVE Recent advances in the fundamental understanding of the complex biology of prostate cancer have provided an increasing number of potential targets for imaging and treatment. The imaging evaluation of prostate cancer needs to be tailored to the various phases of this remarkably heterogeneous disease. CONCLUSION In this article, I review the current state of affairs on a range of PET radiotracers for potential use in the imaging evaluation of men with prostate cancer. PMID:22826388

  9. Roles of Eicosanoids in Prostate Cancer

    PubMed Central

    Nithipatikom, Kasem; Campbell, William B.

    2012-01-01

    Summary Eicosanoids, the metabolites of arachidonic acid, have diverse functions in the regulation of cancer including prostate cancer. This review will provide an overview of the roles of eicosanoids and endocannabinoids and their potential as therapeutic targets for prostate cancer treatment. PMID:24563660

  10. Apoptosis in Prostate Cancer

    DTIC Science & Technology

    2001-04-01

    LNCaP-derived cells unlike their native counterpart have acquired the ability to grow in steroid depleted medium and in castrated hosts. They have...environment of castrated mice is possibly due to selection of dominant alternative mitogenic pathways. The fact that ARR2PB is induced in an AR-dependent... canine model. Cancer Gene Ther 6:456-64, 1999 (12) Koeneman KS, Kao C, Ko SC, Yang L, Wada Y, Kallmes DF, et al: Osteocalcin-directed gene therapy for

  11. Computer-aided detection of prostate cancer.

    PubMed

    Llobet, Rafael; Pérez-Cortés, Juan C; Toselli, Alejandro H; Juan, Alfons

    2007-07-01

    Prostate cancer is one of the most frequent cancers in men and is a major cause of mortality in developed countries. Detection of prostate carcinoma at an early stage is crucial for successful treatment. A method for the analysis of transrectal ultrasound images aimed at computer-aided diagnosis of prostate cancer is tested in this paper. First, two classifiers based on k-nearest neighbors and Hidden Markov models are compared. Second, the diagnostic capacity of our system is tested by means of a set of experiments where humans with varying degrees of experience classified a set of ultrasound images with and without the aid of the computer-aided system. The corpus used in this study was specifically acquired for this purpose. It consists of 4944 ultrasound images corresponding to 303 patients, and is publicly available for non-commercial use upon request. The best classification results achieve an area under the receiver operating characteristic curve of 61.6%. However, the diagnostic capacity of an expert urologist using the computer-aided system improves only slightly compared with his/her capacity without the aid of the system. Despite the difficulty of this task, the obtained results indicate that discrimination between cancerous and non-cancerous tissue is possible to a certain degree. The computer-aided system helps an inexperienced user to make a better diagnosis, however it must be able to perform better in order to be useful in a real-world clinical context.

  12. 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 Logo","field_folder[und]":"15"},"type":"media","attributes":{"alt":"Prostate and Urologic Cancer Research Group Homepage Logo","title":"Prostate and Urologic Cancer Research Group Homepage Logo","height":"266","width":"400","clas | Conducts and supports research on the prevention and early detection of prostate, bladder, and skin cancers.

  13. Two-step amplification of the human PPT sequence provides specific gene expression in an immunocompetent murine prostate cancer model.

    PubMed

    Dzojic, H; Cheng, W-S; Essand, M

    2007-03-01

    The recombinant prostate-specific PPT sequence comprises a prostate-specific antigen enhancer, a PSMA enhancer and a TARP promoter. It is transcriptionally active in human prostate cancer cells both in the presence and absence of testosterone. However, in experimental murine prostate cancer, it has no detectable transcriptional activity. Herein, we describe that the PPT sequence in combination with a two-step transcriptional amplification (TSTA) system becomes active also in murine prostate cancer cells. An adenovirus with TSTA-amplified PPT-controlled expression of the luciferase reporter gene, Ad[PPT/TSTA-Luc], has up to 100-fold higher prostate-specific transcriptional activity than a non-amplified PPT-based adenovirus, Ad[PPT-Luc], in human cells. In addition, Ad[PPT/TSTA-Luc] confers prostate-specific transgene expression in murine cells, with an activity that is approximately 23% of Ad[CMV-Luc] in the transgenic adenocarcinoma of the mouse prostate (TRAMP)-C2 cells. Moreover, to visualize luciferase expression in living mice a charge-coupled device camera was used. Ad[PPT/TSTA-Luc] yielded approximately 30-fold higher transgene expression than Ad[PPT-Luc] in LNCaP tumor xenografts. Importantly, Ad[PPT/TSTA-Luc] also showed activity in murine TRAMP-C2 tumors, whereas Ad[PPT-Luc] activity was undetectable. These results highlight that the recombinant PPT sequence is active in murine prostate cancer cells when augmented by a TSTA system. This finding opens up for preclinical studies with prostate-specific therapeutic gene expression in immunocompetent mice.

  14. The Infectious Pathogenesis of Prostate Cancer

    DTIC Science & Technology

    2010-03-01

    progression; 2-) To characterize the role of the infectious protozoa T. vaginalis in prostate carcinogenesis and progression. The current study is...understanding of the infectious pathogenesis of prostate cancer. Aim II. To characterize the role of the infectious protozoa T. vaginalis in prostate

  15. Prostate cancer radiosensitization through PARP-1 hyperactivation

    PubMed Central

    Dong, Ying; Bey, Erik A.; Li, Long-Shan; Kabbani, Wareef; Yan, Jingsheng; Xie, Xian-Jin; Hsieh, Jer-Tsong; Gao, Jinming; Boothman, David A.

    2010-01-01

    The clinical experimental agent, β-lapachone (Arq 501), can act as a potent radiosensitizer in vitro through an unknown mechanism. In this study, we analyzed the mechanism to determine whether β-lapachone may warrant clinical evaluation as a radiosensitizer. β-lapachone killed prostate cancer cells by NAD(P)H:quinone oxidoreductase 1 (NQO1) metabolic bioactivation, triggering a massive induction of reactive oxygen species (ROS), irreversible DNA single strand breaks (SSBs), PARP-1 hyperactivation, NAD+/ATP depletion, and μ-calpain-induced programmed necrosis. In combination with ionizing radiation (IR), β-lapachone radiosensitized NQO1+ prostate cancer cells, under conditions where nontoxic doses of either agent alone achieved threshold levels of SSBs required for hyperactivation of PARP-1. Combination therapy significantly elevated SSBs, γ-H2AX foci formation, and poly(ADP-ribosylation) of PARP-1, which were associated with ATP loss and induction of μ-calpain-induced programmed cell death. Radiosensitization by β-lapachone was blocked by the NQO1 inhibitor, dicoumarol, or the PARP-1 inhibitor, DPQ. In a mouse xenograft model of prostate cancer, β-lapachone synergized with IR to promote antitumor efficacy. NQO1 levels were elevated in ~60% of human prostate tumors evaluated relative to adjacent normal tissue, where β-lapachone might be efficacious alone or in combination with radiation. Our findings offer a rationale for clinical assessment of β-lapachone (Arq501) as a radiosensitizer in prostate cancers that overexpress NQO1, offering a potentially synergistic targeting strategy to exploit PARP-1 hyperactivation. PMID:20940411

  16. Microsatellite instability in prostate cancer

    SciTech Connect

    Shan, A.L.; Wick, M.J.; Persons, D.L.

    1994-09-01

    Microsatellite instability (MIN) has been documented in hereditary nonpolyposis colorectal cancer (HNPCC) as well as in sporadic forms of human cancers. Two of the genes which appear to be responsible for this particular tumor phenotype, hMSH2 and hMLH1, have now been identified. To determine the potential role of these mutator genes in prostate cancer, we have examined 95 prostate adenocarcinomas (40 paraffin embedded and 55 fresh frozen) for the presence of genetic instability at four microsatellite markers. The markers are localized to chromosome arms 5q(APC-CA1), 8p(Mfd 210Z), 15q(635/636), and 17q(p53-CA). Patients from whom paraffin embedded material was obtained were divided into short term (<3 years, n=18), and long term (>3 years, n=22) survivors. Of the 95 tumors examined, only four tumors (4%) demonstrated MIN: two tumors demonstrated MIN at 3 loci (p53-CA, APC-CA1, 635/636), one tumor demonstrated MIN at 2 loci (APC-CA1 and 635/636), and one tumor demonstrated instability at 635/636 only. All tumors exhibiting MIN had Gleason scores of {ge} 4+4. A correlation between MIN and survival was not observed. Information on family history was limited. However, of the two patients demonstrating MIN at three loci, one patient was diagnosed with a second malignancy (TCC of the ureter), but otherwise had a negative family history, while the second patient had one first degree relative with esophageal cancer. The patient demonstrating MIN at two loci had a negative family history, while the remaining patient had two first degree relatives with cancer (prostate and stomach). These results suggest that hMSH2 and hMLH1 (as reflected by the small percentage of tumors displaying MIN) do not play a prominent role in the process of prostate tumorigenesis.

  17. Gradual reduction of testosterone using a gonadotropin-releasing hormone vaccination delays castration resistance in a prostate cancer model

    PubMed Central

    Barranco, Jesús A. Junco; Millar, Robert P.; Fuentes, Franklin; Bover, Eddy; Pimentel, Eulogio; Basulto, Roberto; Calzada, Lesvia; Morán, Rolando; Rodríguez, Ayni; Garay, Hilda; Reyes, Osvaldo; Castro, Maria D.; Bringas, Ricardo; Arteaga, Niurka; Toudurí, Henio; Rabassa, Mauricio; Fernández, Yairis; Serradelo, Andrés; Hernández, Eduardo; Guillén, Gerardo E.

    2016-01-01

    In a previous study aimed to design a novel prostate cancer vaccine, the authors of the present study demonstrated the advantage of combining the adjuvants Montanide ISA 51 with very small size proteoliposomes (VSSP) to promote a significant humoral immune response to gonadotropin-releasing hormone (GnRH) in healthy animals. The present study compared the efficacy of this vaccine formulation versus the standard treatment currently available in terms of preventing the development of tumors in DD/S mice injected with Shionogi carcinoma (SC) 115 cells. The results demonstrated that 5 non-vaccinated control mice exhibited a fast tumor growth, and succumbed to the disease within 19–31 days. Mice immunized with the GnRH/Montanide ISA 51/VSSP vaccine exhibited a moderate decline in testosterone levels that was associated with a decrease in anti-GnRH antibody titers, which lead to a sustained tumor growth inhibition. In total, 2 mice in the immunized group exhibited complete remission of the tumor for the duration of the present study. In addition, castrated mice, which were used as a control for standard hormonal therapy, exhibited an accelerated decrease in tumor size. However, tumor relapse was observed between days 50 and 54, and between days 65 and 85, following the injection of SC 155 cells. Therefore, these mice were sacrificed at day 90. The present study concludes that the slow and moderate reduction of testosterone levels observed using the GnRH-based vaccine may delay the appearance of castration resistance in a Shionogi prostate cancer model. These findings suggest that this vaccine may be used to delay castration resistance in patients with prostate cancer. PMID:27446378

  18. Gradual reduction of testosterone using a gonadotropin-releasing hormone vaccination delays castration resistance in a prostate cancer model.

    PubMed

    Barranco, Jesús A Junco; Millar, Robert P; Fuentes, Franklin; Bover, Eddy; Pimentel, Eulogio; Basulto, Roberto; Calzada, Lesvia; Morán, Rolando; Rodríguez, Ayni; Garay, Hilda; Reyes, Osvaldo; Castro, Maria D; Bringas, Ricardo; Arteaga, Niurka; Toudurí, Henio; Rabassa, Mauricio; Fernández, Yairis; Serradelo, Andrés; Hernández, Eduardo; Guillén, Gerardo E

    2016-08-01

    In a previous study aimed to design a novel prostate cancer vaccine, the authors of the present study demonstrated the advantage of combining the adjuvants Montanide ISA 51 with very small size proteoliposomes (VSSP) to promote a significant humoral immune response to gonadotropin-releasing hormone (GnRH) in healthy animals. The present study compared the efficacy of this vaccine formulation versus the standard treatment currently available in terms of preventing the development of tumors in DD/S mice injected with Shionogi carcinoma (SC) 115 cells. The results demonstrated that 5 non-vaccinated control mice exhibited a fast tumor growth, and succumbed to the disease within 19-31 days. Mice immunized with the GnRH/Montanide ISA 51/VSSP vaccine exhibited a moderate decline in testosterone levels that was associated with a decrease in anti-GnRH antibody titers, which lead to a sustained tumor growth inhibition. In total, 2 mice in the immunized group exhibited complete remission of the tumor for the duration of the present study. In addition, castrated mice, which were used as a control for standard hormonal therapy, exhibited an accelerated decrease in tumor size. However, tumor relapse was observed between days 50 and 54, and between days 65 and 85, following the injection of SC 155 cells. Therefore, these mice were sacrificed at day 90. The present study concludes that the slow and moderate reduction of testosterone levels observed using the GnRH-based vaccine may delay the appearance of castration resistance in a Shionogi prostate cancer model. These findings suggest that this vaccine may be used to delay castration resistance in patients with prostate cancer.

  19. A tumour control probability model for radiotherapy of prostate cancer using magnetic resonance imaging-based apparent diffusion coefficient maps.

    PubMed

    Casares-Magaz, Oscar; van der Heide, Uulke A; Rørvik, Jarle; Steenbergen, Peter; Muren, Ludvig Paul

    2016-04-01

    Standard tumour control probability (TCP) models assume uniform tumour cell density across the tumour. The aim of this study was to develop an individualised TCP model by including index-tumour regions extracted form multi-parametric magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) maps-based cell density distributions. ADC maps in a series of 20 prostate cancer patients were applied to estimate the initial number of cells within each voxel, using three different approaches for the relation between ADC values and cell density: a linear, a binary and a sigmoid relation. All TCP models were based on linear-quadratic cell survival curves assuming α/β=1.93Gy (consistent with a recent meta-analysis) and α set to obtain a 70% of TCP when 77Gy was delivered to the entire prostate in 35 fractions (α=0.18Gy(-1)). Overall, TCP curves based on ADC maps showed larger differences between individuals than those assuming uniform cell densities. The range of the dose required to reach 50% TCP across the patient cohort was 20.1Gy, 18.7Gy and 13.2Gy using an MRI-based voxel density (linear, binary and sigmoid approach, respectively), compared to 4.1Gy using a constant density. Inclusion of tumour-index information together with ADC maps-based cell density increases inter-patient tumour response differentiation for use in prostate cancer RT, resulting in TCP curves with a larger range in D50% across the cohort compared with those based on uniform cell densities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Role of Mitochondrial Inheritance on Prostate Cancer Outcome in African American Men. Addendum

    DTIC Science & Technology

    2016-11-01

    primers for variable number tandem repeat studies of nuclear Months 6-12 origin 1d. Deplete prostate cancer cells of mitochondria Months...9-24 3 potential cell lines to be used: PNT1A, LNCaP or PC3 1e. Create cytoplasts and fuse with prostate cancer cells devoid of mitochondria ...models were then generated in the PNT1A benign prostate nuclear background. Mitochondria from enucleated metastatic prostate cancer cell line PC3 or

  1. [Trends in Prostate Cancer Epidemiology in Slovakia - an International Comparison].

    PubMed

    Ondrušová, M; Ondruš, D

    According to worldwide estimates, Slovakia is classed as a country with a medium-high incidence of prostate cancer. Current predictions indicate that in the near future prostate cancer will become the most frequent cancer among males in Slovakia. The aims of the study presented in this paper were to analyse trends in the incidence and mortality of prostate cancer in Slovakia and compare these trends with those in other countries and regions of the world, predict epidemiological indicators of prostate cancer in Slovakia, and provide relevant and updated data for the purposes of further analyses and evaluation of the impacts of interventions. National data were analysed for the period 1968-2009. Trends in prostate cancer incidence and mortality were extracted using the joinpoint regression model and are presented with correspoding 95% CI and p values. Predictions of incidence and prevalence were calculated for the years 2014 and 2015, resp. A significant increase in standardized incidence was observed in Slovakia (from 14.5/100,000 in 1980 to 49.0/100,000 in 2009), representing as much as a 6.7% annual percentage change in recent years. The mortality values showed a slower rate of increase, from 9.4/100,000 in 1980 to 13.3/100,000 in 2009, while national mortality of prostate cancer decreased in recent years. These facts have made prostate cancer the most prevalent malignant tumor in males in Slovakia. Unlike in other countries, in Slovakia, no peak in prostate cancer incidence with a subsequent drop is observed. Mortality values reveal a favorable trend in the current national data.Key words: prostate cancer - incidence - mortality - prevalence - clinical stages The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 14. 12. 2016Accepted: 25. 1. 2017.

  2. Finasteride Does Not Increase the Risk of High-grade Prostate Cancer: A Bias-adjusted Modeling Approach

    PubMed Central

    Redman, Mary W.; Tangen, Catherine M.; Goodman, Phyllis J.; Parnes, Howard; Ford, Leslie G.; Lucia, M. Scott; Coltman, Charles A.; Thompson, Ian M.

    2010-01-01

    The Prostate Cancer Prevention Trial found that seven years of administration of finasteride reduced the risk of prostate cancer by 25% but with an apparent increased risk of high grade disease. Subsequent analyses found that finasteride affects cancer detection and improves accuracy of tumor grading at biopsy. We herein estimate the impact of finasteride on the risk of overall and high grade prostate cancer, accounting for these biases. Study endpoints (biopsy-proven cancer or a 7-year end-of-study biopsy) were available in 10,182 of 15,990 subjects assessable for 7-year status and grading information from 500 subjects diagnosed with cancer who underwent radical prostatectomy. Prostate cancer was observed in 22.9% (4.8% with high grade) in the placebo group versus 16.6% (5.8% with high grade) in the finasteride group. In this bias-adjusted analysis, the estimated rates are 21.1% (4.2%) and 14.7% (4.8%), respectively, a 30% risk reduction in prostate cancer (RR =0.70 (95% confidence interval (CI) =0.64-0.76, p<0.0001) and a non-significant 14% increase in high grade cancer (RR=1.14 (95% CI = (0.96-1.35), p=0.12) with finasteride. Incorporating the prostatectomy data, estimated rates of high grade cancers are 8.2% (placebo) versus 6.0% (finasteride), a 27% risk reduction (RR = 0.73 (95% CI=0.56-0.96, p=0.02)) with finasteride. While the observed risk of high grade disease is greater with finasteride, this appears to be through facilitated diagnosis, primarily due to increased biopsy sensitivity. Men undergoing regular prostate cancer screening or who express an interest in cancer prevention should be informed of this prevention opportunity. PMID:19138953

  3. Mitochondria, prostate cancer, and biopsy sampling error.

    PubMed

    Parr, Ryan L; Mills, John; Harbottle, Andrew; Creed, Jennifer M; Crewdson, Gregory; Reguly, Brian; Guimont, François S

    2013-04-01

    Mitochondria and their associated genome are emerging as sophisticated indicators of prostate cancer biology. Alterations in the mitochondrial genome (mtgenome) have been implicated in cell proliferation, metastatic behavior, androgen independence, as a signal for apoptosis, and as a predictor of biochemical recurrence. Somatic mutation patterns in complete mtgenomes are associated with prostate specific antigen levels (PSA) in prostate cancer patients and a large-scale mtgenome deletion (3.4 kb) is consistent with a prostate "cancerization" field effect. This review will focus on the biological characteristics of mitochondria and their direct clinical application to prostate cancer. Mitochondrial science is currently influencing clinical prostate cancer diagnostics and the rapid progress in this area indicates future, break-through contributions in the general field of oncology.

  4. WITHDRAWN: Can the conventional sextant prostate biopsy reliably diagnose unilateral prostate cancer in low-risk, localized, prostate cancer?

    PubMed

    Mayes, J M; Mouraviev, V; Sun, L; Madden, J F; Polascik, T J

    2008-05-13

    The authors hereby retract the e-publication dated 13 May 2008 and entitled, 'Can the conventional sextant prostate biopsy reliably diagnose unilateral prostate cancer in low-risk, localized, prostate cancer?' The authors are submitting a revised version with the same title. This article's statistics were performed for predicting bilateral prostate cancer outcomes. The article was written to help predict unilateral prostate cancer. Although the statistical numbers are correct, they are backwards. We apologize that the statistics indicate a contrary outcome (eg predicting bilateral cancer instead of unilateral disease).

  5. Population model of bladder motion and deformation based on dominant eigenmodes and mixed-effects models in prostate cancer radiotherapy.

    PubMed

    Rios, Richard; De Crevoisier, Renaud; Ospina, Juan D; Commandeur, Frederic; Lafond, Caroline; Simon, Antoine; Haigron, Pascal; Espinosa, Jairo; Acosta, Oscar

    2017-05-01

    In radiotherapy for prostate cancer irradiation of neighboring organs at risk may lead to undesirable side-effects. Given this setting, the bladder presents the largest inter-fraction shape variations hampering the computation of the actual delivered dose vs. planned dose. This paper proposes a population model, based on longitudinal data, able to estimate the probability of bladder presence during treatment, using only the planning computed tomography (CT) scan as input information. As in previously-proposed principal component analysis (PCA) population-based models, we have used the data to obtain the dominant eigenmodes that describe bladder geometric variations between fractions. However, we have used a longitudinal analysis along each mode in order to properly characterize patient's variance from the total population variance. We have proposed is a mixed-effects (ME) model in order to separate intra- and inter-patient variability, in an effort to control confounding cohort effects. Other than using PCA, bladder shapes are represented by using spherical harmonics (SPHARM) that additionally enables data compression without information lost. Based on training data from repeated CT scans, the ME model was thus implemented following dimensionality reduction by means of SPHARM and PCA. We have evaluated the model in a leave-one-out cross validation framework on the training data but also using independent data. Probability maps (PMs) were thus generated with several draws from the learnt model as predicted regions where the bladder will likely move and deform. These PMs were compared with the actual regions using metrics based on mutual information distance and misestimated voxels. The prediction was also compared with two previous population PCA-based models. The proposed model was able to reduce the uncertainties in the estimation of the probable region of bladder motion and deformation. This model can thus be used for tailoring radiotherapy treatments. Copyright

  6. Enigmol: A novel sphingolipid analog with anti-cancer activity against cancer cell lines and in vivo models for intestinal and prostate cancer

    PubMed Central

    Symolon, Holly; Bushnev, Anatoliy; Peng, Qiong; Ramaraju, Harsha; Mays, Suzanne G.; Allegood, Jeremy C.; Pruett, Sarah T.; Sullards, M. Cameron; Dillehay, Dirck L.; Liotta, Dennis C.; Merrill, Alfred H.

    2017-01-01

    Sphingoid bases are cytotoxic for many cancer cell lines, and are thought to contribute to suppression of intestinal tumorigenesis in vivo by ingested sphingolipids. This study explored the behavior of a sphingoid base analog, (2S,3S,5S)-2-amino-3,5-dihydroxyoctadecane (“Enigmol”), that cannot be phosphorylated by sphingosine kinases and is slowly N-acylated, therefore, is more persistent than natural sphingoid bases. Enigmol had potential anti-cancer activity in a National Cancer Institute (NCI-60) cell line screen, and was confirmed to be more cytotoxic and persistent than naturally occurring sphingoid bases using HT29 cells, a colon cancer cell line. Although the molecular targets of sphingoid bases are not well delineated, Enigmol shared one of the mechanisms that has been found for naturally occurring sphingoid bases: to “normalize” the aberrant accumulation of β-catenin in the nucleus and cytoplasm of colon cancer cells due to defect(s) in the adenomatous polyposis coli (APC)/β-catenin regulatory system. Enigmol also had anti-tumor efficacy when administered orally to Min mice, a mouse model with a truncated APC gene product (C57Bl/6JMin/+ mice), decreasing the number of intestinal tumors by half at 0.025 % of the diet (w/w), with no evidence of host toxicity until higher dosages. Enigmol was also tested against the prostate cancer cell lines DU145 and PC-3 in nude mouse xenografts, and suppressed tumor growth in both. Thus, Enigmol represents a novel category of sphingoid base analog that is orally bioavailable and has the potential to be effective against multiple types of cancer. PMID:21398423

  7. Functional Angiogenic Mediators in Prostate Cancer

    DTIC Science & Technology

    2000-08-01

    FUNDING NUMBERS Functional Angiogenic Mediators in Prostate Cancer DAMD17-99- 1 -9521 6. AUTHOR(S) Jennifer A. Doll, Ph.D. 7. PERFORMING ORGANIZATION NAME...transition in the prostate by 1 ) identifying the key angiogenic mediators , 2) investigating the clinical significance of mediator levels in prostatic fluid...our proposal, we set out to 1 ) identify such mediators in the prostate, 2) assess the clinical usefulness of measuring angiogenic mediator levels in

  8. [Active surveillance of prostate cancer].

    PubMed

    Ploussard, G; Hennequin, C; Rozet, F

    2017-10-01

    Several prospective studies have demonstrated the safety of active surveillance as a first treatment of prostate cancer. It spares many patients of a useless treatment, with its potential sequelae. Patients with a low-risk cancer are all candidates for this approach, as recommended by the American Society of Clinical Oncology (ASCO). Some patients with an intermediate risk could be also concerned by active surveillance, but this is still being discussed. Currently, the presence of grade 4 lesions on biopsy is a contra-indication. Modalities included a repeated prostate specific antigen test and systematic rebiopsy during the first year after diagnosis. MRI is now proposed to better select patients at inclusion and also during surveillance. No life style changes or drugs are significantly associated with a longer duration of surveillance. Copyright © 2017. Published by Elsevier SAS.

  9. [Medical treatment of prostate cancer].

    PubMed

    Lobel, B; Cipolla, B; Labrador, J

    1994-03-01

    Hormone dependence of prostate cancer is well known. In 80% of cases with metastases, hormone suppression leads to the reduction of tumour volume and related disorders. However the treatment is generally palliative because malignant process recurs after about around 16 months. Mean survival is less than 3 years in these forms. Lack of response come always together with a poor prognosis, and there is 90% mortality at 2 years. Advanced prostatic cancer should not be treated with hormones if the patient has few symptoms and his quality of life is satisfactory. Symptomatic forms require hormone manipulation. Orchidectomy or LH-RH are recommended. Total androgen ablation (combined treatment) leads rapidly to more relief of symptoms, but its drawbacks and especially high cost indicate that its use should be weighed individually. Estramustine is not a first-lune treatment. Presently, there is no criteria to predict response to treatment.

  10. Reduction of Racial Disparities in Prostate Cancer

    DTIC Science & Technology

    2008-12-01

    inhibitors, aspirin, anti-TNF medications), and other medications of interest (testosterone, finasteride , alpha receptor blockers). 12 We...0.01. There were 14 (7%) control-patients who had finasteride use, with an average of 398.6 doses per individual. None of the prostate cancer...patients had prior finasteride use. In a multiple logistic regression model (Table 2, see supporting materials), after adjustment for the matching

  11. Antitumor activity of tripterine via cell-penetrating peptide-coated nanostructured lipid carriers in a prostate cancer model

    PubMed Central

    Yuan, Ling; Liu, Congyan; Chen, Yan; Zhang, Zhenhai; Zhou, Lei; Qu, Ding

    2013-01-01

    Background The purpose of this study was to evaluate the antitumor effect of cell-penetrating peptide-coated tripterine-loaded nanostructured lipid carriers (CT-NLC) on prostate tumor cells in vitro and in vivo. Methods CT-NLC were developed to improve the hydrophilicity of tripterine. The antiproliferative effects of CT-NLC, tripterine-loaded nanostructured lipid carriers (T-NLC), and free tripterine in a human prostatic carcinoma cell line (PC-3) and a mouse prostate carcinoma cell line (RM-1) were evaluated using an MTT assay. The advantage of CT-NLC over T-NLC and free tripterine with regard to antitumor activity in vivo was evaluated in a prostate tumor-bearing mouse model. The induced tumor necrosis factor-alpha and interleukin-6 cytokine content was investigated by enzyme-linked immunosorbent assay to determine the effect of CT-NLC, T-NLC, and free tripterine on immune responses. Histologic and TUNEL assays were carried out to investigate the mechanisms of tumor necrosis and apoptosis. Results CT-NLC, T-NLC, and free tripterine showed high antiproliferative activity in a dose-dependent manner, with an IC50 of 0.60, 0.81, and 1.02 μg/mL in the PC-3 cell line and 0.41, 0.54, and 0.89 μg/mL in the RM-1 cell line after 36 hours. In vivo, the tumor inhibition rates for cyclophosphamide, high-dose (4 mg/kg) and low-dose (2 mg/kg) tripterine, high-dose (4 mg/kg) and low-dose (2 mg/kg) T-NLC, high-dose (4 mg/kg) and low-dose (2 mg/kg) CT-NLC were 76.51%, 37.07%, 29.53%, 63.56%, 48.25%, 72.68%, and 54.50%, respectively, showing a dose-dependent pattern. The induced tumor necrosis factor-alpha and interleukin-6 cytokine content after treatment with CT-NLC and T-NLC was significantly higher than that of high-dose tripterine. Moreover, CT-NLC showed the expected advantage of inducing necrosis and apoptosis in prostate tumor cells. Conclusion CT-NLC noticeably enhanced antitumor activity in vitro and in vivo and showed dramatically improved cytotoxicity in normal cells

  12. Docetaxel-carboxymethylcellulose nanoparticles display enhanced anti-tumor activity in murine models of castration-resistant prostate cancer.

    PubMed

    Hoang, Bryan; Ernsting, Mark J; Murakami, Mami; Undzys, Elijus; Li, Shyh-Dar

    2014-08-25

    Docetaxel (DTX) remains the only effective drug for prolonging survival and improving quality of life of metastatic castration resistant prostate cancer (mCRPC) patients. Despite some clinical successes with DTX-based therapies, advent of cumulative toxicity and development of drug resistance limit its long-term clinical application. The integration of nanotechnology for drug delivery can be exploited to overcome the major intrinsic limitations of DTX therapy for mCRPC. We evaluated whether reformulation of DTX by facile conjugation to carboxymethylcellulose nanoparticles (Cellax) can improve the efficacy and safety of the drug in s.c. and bone metastatic models of CRPC. A single dose of the nanoparticles completely regressed s.c. PC3 tumor xenografts in mice. In addition, Cellax elicited fewer side effects compared to native DTX. Importantly, Cellax did not increase the expression of drug resistance molecules in androgen-independent PC3 prostate cancer cells in comparison with DTX. Lastly, in a bone metastatic model of CRPC, Cellax treatment afforded a 2- to 3-fold improvement in survival and enhancements in quality-of-life of the animals over DTX and saline controls. These results demonstrate the potential of Cellax in improving the treatment of mCRPC. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Vaccine Immunotherapy for Prostate Cancer

    DTIC Science & Technology

    2006-07-01

    opinions and/or findings contained in this report are those of the author( s ) and should not be construed as an official Department of the Army position...Vaccine Immunotherapy for Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-05-1-0462 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ...NAME( S ) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER University of Iowa Iowa City, IA 52242 9. SPONSORING

  14. Prostate Cancer Research Training Program

    DTIC Science & Technology

    2011-05-01

    this laboratory concentrates on the area of tumor immunology with an emphasis on immunotherapy. We have constructed microbial vaccines to be used...to the transgene product induced by the vaccine are underway. Additionally, we are carrying our "translational" research in the form of clinical...trials of our adenovirus vaccine in men with prostate cancer. Important in these trials is the safety of the vaccine and its ability to induce anti

  15. Prostate Cancer Research Training Program

    DTIC Science & Technology

    2012-05-01

    i mmunology with an emphasis on immunotherapy. We ha ve constructed microbial vaccines to be used for the investigation of gene and immunotherapy... vaccine are underway. Additionally, we are carrying our "translational" research in the fo rm of clinical trials of our adenovirus vaccine in men with...prostate cancer. Important in thes e trials is the safety of the vaccine and its ability to in duce anti-tumor immunity. We have recently completed

  16. Utility of ADC measurement on diffusion-weighted MRI in differentiation of prostate cancer, normal prostate and prostatitis.

    PubMed

    Esen, Meltem; Onur, Mehmet Ruhi; Akpolat, Nusret; Orhan, Irfan; Kocakoc, Ercan

    2013-08-01

    To determine the utility of apparent diffusion coefficient (ADC) values in differentiation of prostate cancer from normal prostate parenchyma and prostatitis we obtained ADC values of 50 patients at b 100, 600 and 1,000 s/mm(2) diffusion gradients. The ADC values of prostate cancer group were significantly lower than normal prostate and prostatitis group at b 600 and 1,000 s/mm(2) gradients. The ADC values at high diffusion gradients may be used in differentiation prostate cancer from normal prostate and prostatitis.

  17. 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.

  18. 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

  19. Multiparametric magnetic resonance imaging and active surveillance: How to better select insignificant prostate cancer?

    PubMed

    Porpiglia, Francesco; Cantiello, Francesco; De Luca, Stefano; De Pascale, Agostino; Manfredi, Matteo; Mele, Fabrizio; Bollito, Enrico; Cirillo, Stefano; Damiano, Rocco; Russo, Filippo

    2016-09-01

    To evaluate the role of multiparametric magnetic resonance imaging in improving the predictive accuracy of the Prostate Cancer Research International: Active Surveillance and Epstein criteria for active surveillance in prostate cancer. A retrospective study was carried out with 126 prostate cancer patients treated with robot-assisted radical prostatectomy, but eligible for active surveillance according to the Prostate Cancer Research International: Active Surveillance criteria; 63 patients were also eligible according to the Epstein criteria. All patients underwent preoperative multiparametric magnetic resonance imaging, after at least 6 weeks from biopsy. The images from the multiparametric magnetic resonance imaging were assessed, and diagrams showing prostate sextants were used to designate regions of abnormalities within the prostate. Findings in the prostate were assigned to one of five categories according the Prostate Imaging-Reporting and Data System guidelines (v1.0), and considered positive for prostate cancer if the final Prostate Imaging-Reporting and Data System guidelines were >3 and negative if ≤3. Multivariate logistic regression analysis was carried out to evaluate the gain in accuracy of the Prostate Cancer Research International: Active Surveillance and Epstein criteria when added to multiparametric magnetic resonance imaging. Decision curve analysis was carried out to identify the net benefit of each model. The inclusion of multiparametric magnetic resonance imaging to the Epstein criteria and the Prostate Cancer Research International: Active Surveillance multivariate model significantly increased their accuracy in predicting pathologically-confirmed insignificant prostate cancer by 7% and 5%, respectively. At the decision curve analysis evaluation, the model including the Prostate Cancer Research International: Active Surveillance criteria and multiparametric magnetic resonance imaging improved the clinical risk prediction over the other

  20. Bone Matrix Osteonectin Limits Prostate Cancer Cell Growth and Survival

    PubMed Central

    Kapinas, Kristina; Lowther, Katie M.; Kessler, Catherine B.; Tilbury, Karissa; Lieberman, Jay R.; Tirnauer, Jennifer S.; Campagnola, Paul; Delany, Anne M.

    2012-01-01

    There is considerable interest in understanding prostate cancer metastasis to bone and the interaction of these cells with the bone microenvironment. Osteonectin/SPARC/BM-40 is a collagen binding matricellular protein that is enriched in bone. Its expression is increased in prostate cancer metastases, and it stimulates the migration of prostate carcinoma cells. However, the presence of osteonectin in cancer cells and the stroma may limit prostate tumor development and progression. To determine how bone matrix osteonectin affects the behavior of prostate cancer cells, we modeled prostate cancer cell-bone interactions using the human prostate cancer cell line PC-3, and mineralized matrices synthesized by wild type and osteonectin-null osteoblasts in vitro. We developed this in vitro system because the structural complexity of collagen matrices in vivo is not mimicked by reconstituted collagen scaffolds or by more complex substrates, like basement membrane extracts. Second harmonic generation imaging demonstrated that the wild type matrices had thick collagen fibers organized into longitudinal bundles, whereas osteonectin-null matrices had thinner fibers in random networks. Importantly, a mouse model of prostate cancer metastases to bone showed a collagen fiber phenotype similar to the wild type matrix synthesized in vitro. When PC-3 cells were grown on the wild type matrices, they displayed decreased cell proliferation, increased cell spreading, and decreased resistance to radiation-induced cell death, compared to cells grown on osteonectin-null matrix. Our data support the idea that osteonectin can suppress prostate cancer pathogenesis, expanding this concept to the microenvironment of skeletal metastases. PMID:22525512

  1. A small molecule polyamine oxidase inhibitor blocks androgen-induced oxidative stress and delays prostate cancer progression in the transgenic adenocarcinoma of the mouse prostate model.

    PubMed

    Basu, Hirak S; Thompson, Todd A; Church, Dawn R; Clower, Cynthia C; Mehraein-Ghomi, Farideh; Amlong, Corey A; Martin, Christopher T; Woster, Patrick M; Lindstrom, Mary J; Wilding, George

    2009-10-01

    High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiologic factor in prostate cancer (CaP) occurrence, recurrence, and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase, the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells, as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data show that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays CaP progression.

  2. PRODIGE: PRediction models in prOstate cancer for personalized meDIcine challenGE.

    PubMed

    Alitto, A R; Gatta, R; Vanneste, Bgl; Vallati, M; Meldolesi, E; Damiani, A; Lanzotti, V; Mattiucci, G C; Frascino, V; Masciocchi, C; Catucci, F; Dekker, A; Lambin, P; Valentini, V; Mantini, G

    2017-07-31

    Identifying the best care for a patient can be extremely challenging. To support the creation of multifactorial Decision Support Systems (DSSs), we propose an Umbrella Protocol, focusing on prostate cancer. The PRODIGE project consisted of a workflow for standardizing data, and procedures, to create a consistent dataset useful to elaborate DSSs. Techniques from classical statistics and machine learning will be adopted. The general protocol accepted by our Ethical Committee can be downloaded from cancerdata.org . A standardized knowledge sharing process has been implemented by using a semi-formal ontology for the representation of relevant clinical variables. The development of DSSs, based on standardized knowledge, could be a tool to achieve a personalized decision-making.

  3. Linking Estrogens, Prostatitis and Prostate Cancer

    DTIC Science & Technology

    2009-03-01

    provide the first direct evidence linking phy siologic estr ogen up- regulation an d pr ostate ma lignancy via inflammation. Ellem, Stuart J...inflammation and malignancy in the prostate. The identification of estr ogen as a cause of prostatitis, as well as a fac tor in the development of

  4. Prostate Cancer Evaluation: Design, Synthesis and Evaluation of Novel Enzyme-Activated Proton MRI Contrast Agents

    DTIC Science & Technology

    2010-10-01

    Bladou F, Hassoun J, Maitland N, Mannoni P, Bagnis C, 2003, Expression of a model gene in prostate cancer cells lentivirally transduced in vitro and...in vivo, Prostate Cancer and Prostatic Diseases, 6, 228-234. 22. Stanbridge LJ, Dussupt V, Maitland NJ, 2003, Baculoviruses as vectors for gene

  5. Caveolin-1 and prostate cancer progression.

    PubMed

    Freeman, Michael R; Yang, Wei; Di Vizio, Dolores

    2012-01-01

    Caveolin-1 was identified in the 1990s as a marker of aggressive prostate cancer. The caveolin-1 protein localizes to vesicular structures called caveolae and has been shown to bind and regulate many signaling proteins involved in oncogenesis. Caveolin-1 also has lipid binding properties and mediates aspects of cholesterol and fatty acid metabolism and can elicit biological responses in a paracrine manner when secreted. Caveolin-1 is also present in the serum of prostate cancer patients and circulating levels correlate with extent of disease. Current evidence indicates that increased expression of caveolin-1 in prostate adenocarcinoma cells and commensurate downregulation of the protein in prostate stroma, mediate progression to the castration-resistant phase of prostate cancer through diverse pathways. This chapter summarizes the current state of our understanding of the cellular and physiologic mechanisms in which caveolin-1 participates in the evolution of prostate cancer cell phenotypes.

  6. Epigenetics in breast and prostate cancer.

    PubMed

    Wu, Yanyuan; Sarkissyan, Marianna; Vadgama, Jaydutt V

    2015-01-01

    Most recent investigations into cancer etiology have identified a key role played by epigenetics. Specifically, aberrant DNA and histone modifications which silence tumor suppressor genes or promote oncogenes have been demonstrated in multiple cancer models. While the role of epigenetics in several solid tumor cancers such as colorectal cancer are well established, there is emerging evidence that epigenetics also plays a critical role in breast and prostate cancer. In breast cancer, DNA methylation profiles have been linked to hormone receptor status and tumor progression. Similarly in prostate cancer, epigenetic patterns have been associated with androgen receptor status and response to therapy. The regulation of key receptor pathways and activities which affect clinical therapy treatment options by epigenetics renders this field high priority for elucidating mechanisms and potential targets. A new set of methylation arrays are now available to screen epigenetic changes and provide the cutting-edge tools needed to perform such investigations. The role of nutritional interventions affecting epigenetic changes particularly holds promise. Ultimately, determining the causes and outcomes from epigenetic changes will inform translational applications for utilization as biomarkers for risk and prognosis as well as candidates for therapy.

  7. Epigenetics in Breast and Prostate Cancer

    PubMed Central

    Wu, Yanyuan; Sarkissyan, Marianna; Vadgama, Jaydutt V.

    2015-01-01

    SUMMARY Most recent investigations into cancer etiology have identified a key role played by epigenetics. Specifically, aberrant DNA and histone modifications which silence tumor suppressor genes or promote oncogenes have been demonstrated in multiple cancer models. While the role of epigenetics in several solid tumor cancers such as colorectal cancer are well established, there is emerging evidence that epigenetics also plays a critical role in breast and prostate cancer. In breast cancer, DNA methylation profiles have been linked to hormone receptor status and tumor progression. Similarly in prostate cancer, epigenetic patterns have been associated with androgen receptor status and response to therapy. The regulation of key receptor pathways and activities which affect clinical therapy treatment options by epigenetics renders this field high priority for elucidating mechanisms and potential targets. A new set of methylation arrays are now available to screen epigenetic changes and provide the cuttingedge tools needed to perform such investigations. The role of nutritional interventions affecting epigenetic changes particularly holds promise. Ultimately, determining the causes and outcomes from epigenetic changes will inform translational applications for utilization as biomarkers for risk and prognosis as well as candidates for therapy. PMID:25421674

  8. Vietnam military service history and prostate cancer

    PubMed Central

    Justine, Leavy; Gina, Ambrosini; Lin, Fritschi

    2006-01-01

    Background Three decades after US and Australian forces withdrew from Vietnam, there has been much public interest in the health consequences of service in Vietnam. One controversial question is whether the risk of prostate cancer amongst Vietnam veterans is increased. This paper examines relationships between military history, family history and risk of prostate cancer in a population-based case control study. Methods Cases were selected from the Cancer Registry of Western Australia as incident cases of histologically-confirmed prostate cancer, and controls were age-matched and selected from the Western Australian electoral roll. Study participants were asked to report any military service history and details about that service. Results Between January 2001 and September 2002, 606 cases and 471 controls aged between 40–75 years were recruited. An increased prostate cancer risk was observed in men reporting they were deployed in Vietnam although this was not statistically significant (OR = 2.12; 95% CI 0.88–5.06). An increased risk was also observed in men reporting prostate cancer in fathers (OR = 1.90; 95% CI 1.20–3.00) or brothers (OR = 2.05; 95% CI 1.20–3.50) diagnosed with prostate cancer. Conclusion These findings support a positive association between prostate cancer and military service history in the Vietnam war and a first degree relative family history of prostate cancer. PMID:16556325

  9. 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

  10. Dietary Antioxidants and Prostate Cancer: A Review

    PubMed Central

    Vance, Terrence M.; Su, Joseph; Fontham, Elizabeth T. H.; Koo, Sung I.; Chun, Ock K.

    2013-01-01

    Prostate cancer is the most common non-cutaneous cancer in men in the United States. Several studies have examined the relationship between prostate cancer and antioxidants; however, the results of these studies are inconsistent. This article provides a systematic review of studies on prostate cancer and antioxidant intake from diet and supplements. Tea and coffee appear to offer protection against advanced prostate cancer. Different forms of vitamin E appear to exert different effects on prostate cancer, with alpha-tocopherol potentially increasing and gamma-tocopherol potentially decreasing risk of the disease. There is no strong evidence for a beneficial effect of selenium, vitamin C, or beta-carotene, while lycopene appears to be negatively associated with risk of the disease. The effect of dietary antioxidants on prostate cancer remains undefined and inconclusive, with different antioxidants affecting prostate cancer risk differentially. Further studies are needed to clarify the relationship between antioxidants and prostate cancer risk and to delineate the underlying mechanisms. PMID:23909722

  11. 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

  12. Prostate Cancer: How Young is too Young?

    PubMed Central

    Gupta, Sahil; Gupta, Arjun; Saini, Ashish K.; Majumder, Kaustav; Sinha, Kalpana; Chahal, Anurag

    2017-01-01

    Prostate cancer is the most common non-cutaneous malignancy in men. It is generally considered a cancer of the elderly, and the median age of presentation is 68 years. However 10% of new diagnoses in the USA occur in men aged ≤ 55 years. This may be due to more prevalent screening nowadays, and may also reflect the diagnosis of an increasingly recognized but underappreciated entity, i.e. early-onset prostate cancer. Patients with early onset prostate cancer pose unique challenges. Current data suggest that early-onset prostate cancer is a distinct phenotype—from both an etiological and clinical perspective— that deserves further attention. We present a case of a 28-year-old man who presented with lower urinary tract symptoms and was diagnosed with advanced stage prostate cancer. PMID:28413383

  13. 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

  14. Review of selenium and prostate cancer prevention.

    PubMed

    Yang, Lei; Pascal, Mouracade; Wu, Xiao-Hou

    2013-01-01

    Prostate cancer is the most common malignancy in men in the United States. Surgery or radiation are sometimes unsatisfactory treatments because of the complications such as incontinence or erectile dysfunction. Selenium was found to be effective to prevent prostate cancer in the Nutritional Prevention of Cancer Trial (NPC), which motivated two other clinical trials: the Selenium and Vitamin E Cancer Prevention Trial (SELECT) and a Phase III trial of selenium to prevent prostate cancer in men with high-grade prostatic intraepithelial neoplasia. However, these two trials failed to confirm the results of the NPC trial and indicated that the selenium may not be preventive of prostate cancer. In this article we review the three clinical trials and discuss some different points which might be potential factors underlying variation in results obtained.

  15. 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.

  16. Alcoholic Beverages and Prostate Cancer in a Prospective US Cohort Study

    PubMed Central

    Watters, Joanne L.; Park, Yikyung; Hollenbeck, Albert; Schatzkin, Arthur; Albanes, Demetrius

    2010-01-01

    Despite numerous investigations, the correlation between alcohol consumption and prostate cancer risk remains uncertain. This report investigated the association between alcohol use and prostate cancer risk in a prospective cohort study of 294,707 US men aged 50–71 years in 1995–1996. Cox proportional hazards regression models with hazard ratios and 95% confidence intervals were adjusted for characteristics including age, race, body mass index, physical activity, and family history of prostate cancer, as well as testing for prostate-specific antigen and a digital rectal examination. There were 15,327 nonadvanced and 1,900 advanced prostate cancers identified through 2003 and 514 fatal cases through 2005. Risk of nonadvanced prostate cancer was 25% higher for men consuming ≥6 drinks daily (hazard ratio = 1.25, 95% confidence interval: 1.13, 1.37), 19% higher for men consuming 3–<6 drinks daily, and 6% higher for men consuming up to 3 drinks daily, compared with nondrinkers. The association between alcohol consumption and nonadvanced prostate cancer risk did not differ appreciably by age, family history of prostate cancer, smoking status, body mass index, or self-reported prostate-specific antigen testing and digital rectal examination (the latter available for >60% of respondents). The authors observed no association between alcohol intake and advanced prostate cancer and an inverse association with fatal prostate cancer among heavy drinkers. These findings suggest that higher alcohol consumption modestly increases nonadvanced prostate cancer risk. PMID:20813803

  17. Alcoholic beverages and prostate cancer in a prospective US cohort study.

    PubMed

    Watters, Joanne L; Park, Yikyung; Hollenbeck, Albert; Schatzkin, Arthur; Albanes, Demetrius

    2010-10-01

    Despite numerous investigations, the correlation between alcohol consumption and prostate cancer risk remains uncertain. This report investigated the association between alcohol use and prostate cancer risk in a prospective cohort study of 294,707 US men aged 50-71 years in 1995-1996. Cox proportional hazards regression models with hazard ratios and 95% confidence intervals were adjusted for characteristics including age, race, body mass index, physical activity, and family history of prostate cancer, as well as testing for prostate-specific antigen and a digital rectal examination. There were 15,327 nonadvanced and 1,900 advanced prostate cancers identified through 2003 and 514 fatal cases through 2005. Risk of nonadvanced prostate cancer was 25% higher for men consuming ≥6 drinks daily (hazard ratio = 1.25, 95% confidence interval: 1.13, 1.37), 19% higher for men consuming 3-<6 drinks daily, and 6% higher for men consuming up to 3 drinks daily, compared with nondrinkers. The association between alcohol consumption and nonadvanced prostate cancer risk did not differ appreciably by age, family history of prostate cancer, smoking status, body mass index, or self-reported prostate-specific antigen testing and digital rectal examination (the latter available for >60% of respondents). The authors observed no association between alcohol intake and advanced prostate cancer and an inverse association with fatal prostate cancer among heavy drinkers. These findings suggest that higher alcohol consumption modestly increases nonadvanced prostate cancer risk.

  18. A real time online assessment system with modelized architecture on clinical infometrics for patient reported outcomes of prostate cancer.

    PubMed

    Lin, Hsueh-Chun; Wu, Hsi-Chin; Chang, Chih-Hung; Li, Tsai-Chung; Liang, Wen-Miin; Wang, Jong-Yi

    2012-06-01

    The aim of this study was to establish a real time online health and decision support system with the novel information technology integrating modelized architecture and Web services for clinical infometrics on patient reported outcome (PRO) and quality of life (QOL) for prostate cancer patients. The patient-oriented interface was practiced with object relation mapping (ORM) and clinical data warehouse to collaborate QOL measurement and medical informatics through internet by incorporating a variety of hospital information systems. The conceptual infrastructure was designed by five primary layers to organize the data flow of online assessment and clinical data for real-time decision support. A preliminary knowledge bank was formed by feedback of expert opinions to provide online guidance for decision references. Observation and assessment of prostate cancer patients' QOL and clinical markers were immediately tracked with automatic computation algorithm to improve health care quality in the treatment cycle. The established Web-based system can help clinicians concurrently collect and analyze real-time PROs and QOL for enhancing communication with patients and improving the quality of care. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  19. Can homeopathic treatment slow prostate cancer growth?

    PubMed

    Jonas, Wayne B; Gaddipati, Jaya P; Rajeshkumar, N V; Sharma, Anuj; Thangapazham, Rajesh L; Warren, Jim; Singh, Anoop K; Ives, John A; Olsen, Cara; Mog, Steven R; Maheshwari, Radha K

    2006-12-01

    Homeopathy is a complementary medicine widely used around the world. Despite extensive use of homeopathy for cancer and other serious conditions with reported success, clinical and laboratory research has been equivocal, and no rigorous research has been done on cancer. In 1999, the US National Cancer Institute evaluated the effects of homeopathic treatment of cancer from a clinic in India and has released a request for protocols to conduct further research into this treatment. Therefore, the authors conducted a series of carefully controlled laboratory studies evaluating the effects of commonly used homeopathic remedies in cell and animal models of prostate cancer. One hundred male Copenhagen rats were randomly assigned to either treatment or control groups after inoculation with prostate tumor cells. Prostate tumor cells DU-145, LNCaP, and MAT-LyLu were exposed to 5 homeopathic remedies. Male Copenhagen rats were injected with MAT-LyLu cells and exposed to the same homeopathic remedies for 5 weeks. In vitro outcomes included tumor cell viability and apoptosis gene expression. In vivo outcomes included tumor incidence, volume, weight, total mortality, proliferating cell nuclear antigen (PCNA) expression, apoptotic cell death (terminal deoxynucleotidyl transferase mediated d-uridine triphosphate nick end labeling), and gene expression (rAPO-multiprobe). There were no effects on cell viability or gene expression in 3 prostate cell lines with any remedies at any exposure time. There was a 23% reduction in tumor incidence (P < .0001), and for animals with tumors, there was a 38% reduction in tumor volume in homeopathy-treated animals versus controls (P < .02). At time of killing, experimental animals with tumors had a 13% lower average tumor weight (P < .05). Tumors in these treated animals showed a 19% increase in apoptotic cell death (P < .05) and reduced PCNA-positive cells. The findings indicate that selected homeopathic remedies for the present study have no

  20. Prognostic factors in prostate cancer.

    PubMed

    Braeckman, Johan; Michielsen, Dirk

    2007-01-01

    In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before

  1. 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.

  2. Systems Modeling of Anti-apoptotic Pathways in Prostate Cancer: Psychological Stress Triggers a Synergism Pattern Switch in Drug Combination Therapy

    PubMed Central

    Sun, Xiaoqiang; Bao, Jiguang; Nelson, Kyle C.; Li, King Chuen; Kulik, George; Zhou, Xiaobo

    2013-01-01

    Prostate cancer patients often have increased levels of psychological stress or anxiety, but the molecular mechanisms underlying the interaction between psychological stress and prostate cancer as well as therapy resistance have been rarely studied and remain poorly understood. Recent reports show that stress inhibits apoptosis in prostate cancer cells via epinephrine/beta2 adrenergic receptor/PKA/BAD pathway. In this study, we used experimental data on the signaling pathways that control BAD phosphorylation to build a dynamic network model of apoptosis regulation in prostate cancer cells. We then compared the predictive power of two different models with or without the role of Mcl-1, which justified the role of Mcl-1 stabilization in anti-apoptotic effects of emotional stress. Based on the selected model, we examined and quantitatively evaluated the induction of apoptosis by drug combination therapies. We predicted that the combination of PI3K inhibitor LY294002 and inhibition of BAD phosphorylation at S112 would produce the best synergistic effect among 8 interventions examined. Experimental validation confirmed the effectiveness of our predictive model. Moreover, we found that epinephrine signaling changes the synergism pattern and decreases efficacy of combination therapy. The molecular mechanisms responsible for therapeutic resistance and the switch in synergism were explored by analyzing a network model of signaling pathways affected by psychological stress. These results provide insights into the mechanisms of psychological stress signaling in therapy-resistant cancer, and indicate the potential benefit of reducing psychological stress in designing more effective therapies for prostate cancer patients. PMID:24339759

  3. Differentiation of Neonatal Human-Induced Pluripotent Stem Cells to Prostate Epithelial Cells: A Model to Study Prostate Cancer Development

    DTIC Science & Technology

    2014-06-01

    expression by RT-PCR showed that while human dermal fibroblasts have higher constitutive expression of Nanog, Oct4 and Sox2 compared to IMP90 cells...REPORT U b . ABSTRACT U c. THIS PAGE U UU 12 19b. TELEPHONE NUMBER (include area code) 4 TABLE OF CONTENTS: Item...mechanistic insights into prostate epithelial cell development can be gained. 8 a. DPYS DAY!O b . c. Fig. 1. Differentiation of human iPSC to

  4. 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

  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. 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.

  7. Does obesity modify prostate cancer detection in a European cohort?

    PubMed Central

    Morales-Palacios, Nelson; Barrionuevo-Gonzalez, Marta; Ortega-Polledo, Luis-Enrique; Ortiz-Vico, Francisco-Javier; Sanchez-Chapado, Manuel

    2017-01-01

    Introduction To investigate prostate-specific antigen (PSA) accuracy and digital rectal examination (DRE) accuracy in detecting prostate cancer according to body mass index (BMI) in Spanish men with an indication of the first prostate biopsy. Material and methods We reviewed the clinical and histopathological data of 1,319 patients who underwent transrectal ultrasound-guided prostate needle biopsy. The patients were categorised according to the BMI as follows: <25 kg/m2 (normal weight); 25–29.9 kg/m2 (overweight); and ≥30 kg/m2 (obese). Receiver operator characteristic curves were used to assess PSA accuracy and DRE accuracy by calculating the area under the curve. Results The obesity rate of the cohort was 14%. PSA accuracy for predicting prostate cancer in each BMI category was 0.52, 0.58 and 0.62, respectively (p = 0.01). After stratification by DRE findings, there was no difference in the performance accuracy of PSA in predicting the presence of cancer across BMI groups in abnormal DRE (p = 0.90). Serum PSA, DRE and BMI were strong predictors of prostate cancer diagnosis (odds ratio 1.07, 2.02 and 1.4, respectively; p <0.001). When the DRE was abnormal, a BMI ≥30 increased the risk of prostate cancer twice. With the addition of BMI to the model, the area under the curve of the combined PSA and DRE for diagnosing prostate cancer improved from 0.60 to 0.63. Conclusions The predictive value of PSA in predicting prostate cancer is not poorer in the obese population and the predictive value of an abnormal DRE in cancer detection is significantly modified by the patient’s BMI. PMID:28461985

  8. Does obesity modify prostate cancer detection in a European cohort?

    PubMed

    Sanchis-Bonet, Angeles; Morales-Palacios, Nelson; Barrionuevo-Gonzalez, Marta; Ortega-Polledo, Luis-Enrique; Ortiz-Vico, Francisco-Javier; Sanchez-Chapado, Manuel

    2017-01-01

    To investigate prostate-specific antigen (PSA) accuracy and digital rectal examination (DRE) accuracy in detecting prostate cancer according to body mass index (BMI) in Spanish men with an indication of the first prostate biopsy. We reviewed the clinical and histopathological data of 1,319 patients who underwent transrectal ultrasound-guided prostate needle biopsy. The patients were categorised according to the BMI as follows: <25 kg/m(2) (normal weight); 25-29.9 kg/m(2) (overweight); and ≥30 kg/m(2) (obese). Receiver operator characteristic curves were used to assess PSA accuracy and DRE accuracy by calculating the area under the curve. The obesity rate of the cohort was 14%. PSA accuracy for predicting prostate cancer in each BMI category was 0.52, 0.58 and 0.62, respectively (p = 0.01). After stratification by DRE findings, there was no difference in the performance accuracy of PSA in predicting the presence of cancer across BMI groups in abnormal DRE (p = 0.90). Serum PSA, DRE and BMI were strong predictors of prostate cancer diagnosis (odds ratio 1.07, 2.02 and 1.4, respectively; p <0.001). When the DRE was abnormal, a BMI ≥30 increased the risk of prostate cancer twice. With the addition of BMI to the model, the area under the curve of the combined PSA and DRE for diagnosing prostate cancer improved from 0.60 to 0.63. The predictive value of PSA in predicting prostate cancer is not poorer in the obese population and the predictive value of an abnormal DRE in cancer detection is significantly modified by the patient's BMI.

  9. [Second cancer after starting treatment for prostate cancer].

    PubMed

    Mikata, Noriharu; Imao, Sadao; Fukasawa, Ritu

    2002-08-01

    The subjects for the present study were 270 patients with prostate cancer who underwent initial treatment at our hospital over the 14 years from 1986 to 1999. They were investigated to assess the relationship between their treatment and metachronous tumors. Sixteen patients (5.9%) developed cancer of other organs after starting treatment for prostate cancer. These metachronous tumors included gastric cancer in six patients as well as lung cancer, esophageal cancer, colorectal cancer, liver cancer, renal cancer, bladder cancer, skin cancer, leukemia, and mediastinal adenocarcinoma. Treatment for prostate cancer other than surgery included radiotherapy in eight patients, administration of estramustine phosphate sodium in nine patients, and LH-RH analogues in six patients. The chi-square test showed no significant difference in the incidence of metachronous cancer in relation to the presence/absence of these three therapies. The present study therefore ruled out the possible induction of other tumors by treatment for prostate cancer.

  10. A novel spontaneous model of epithelial-mesenchymal transition (EMT) using a primary prostate