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Sample records for prostate cancer models

  1. 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.

  2. 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 ...

  3. 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

  4. What is Prostate Cancer?

    MedlinePlus

    ... Research? Prostate Cancer About Prostate Cancer What Is Prostate Cancer? Cancer starts when cells in the body begin ... through the center of the prostate. Types of prostate cancer Almost all prostate cancers are adenocarcinomas . These cancers ...

  5. 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.

  6. 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 ...

  7. 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.

  8. 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

  9. 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

  10. 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 ...

  11. 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.

  12. 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.

  13. [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.

  14. 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

  15. 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

  16. Prostate cancer

    MedlinePlus

    ... If the cancer has not spread outside the prostate gland, common treatments include: Surgery ( radical prostatectomy ) Radiation therapy , including brachytherapy and proton therapy If you are older, your doctor may recommend simply monitoring the cancer with PSA tests and biopsies. Hormone therapy is ...

  17. 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.

  18. 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/ ...

  19. 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.

  20. 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

  1. Novel Prostate Cancer Pathway Modeling using Boolean Implication

    DTIC Science & Technology

    2012-09-01

    standard diagnostic marker for prostate cancer despite its serious limitations. Large proportions of men are being diagnosed with prostate cancer but...recent studies imply that many of them don’t need prostate cancer treatment. There is clearly a need for better diagnostic and prognostic marker in...discovery of better diagnostic and prognostic markers . Body Previously, we have published a novel approach to discover Boolean implications

  2. 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 ...

  3. Prostate Cancer Symptoms

    MedlinePlus

    ... PCF? Featured Blue Jacket Fashion Show Contact Us Prostate Cancer Symptoms The conversation about PSA screening really applies ... That’s why screening is such an important topic. Prostate Cancer Basics About the Prostate Risk Factors Prevention Symptoms ...

  4. 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 ...

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. Vaccine Treatment for Prostate Cancer

    MedlinePlus

    ... Back After Treatment Prostate Cancer Treating Prostate Cancer Vaccine Treatment for Prostate Cancer Sipuleucel-T (Provenge) is ... less advanced prostate cancer. Possible side effects of vaccine treatment Side effects from the vaccine tend to ...

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. Prostate Cancer Screening

    MedlinePlus

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

  15. 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 ...

  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. 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.

  18. 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

  19. Living with Prostate Cancer

    MedlinePlus

    ... cancer treatment and can improve many aspects of health, including muscle strength, balance, fatigue, cardiovascular fitness, and depression. Physical activity after a prostate cancer diagnosis is linked to ...

  20. 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.

  1. 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

  2. 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.

  3. Can Prostate Cancer Be Found Early?

    MedlinePlus

    ... Prostate Cancer Early Detection, Diagnosis, and Staging Can Prostate Cancer Be Found Early? Screening is testing to find ... Health Care Team About Prostate Cancer? More In Prostate Cancer About Prostate Cancer Causes, Risk Factors, and Prevention ...

  4. Screening for prostate cancer

    NASA Technical Reports Server (NTRS)

    Weirich, Stephen A.

    1993-01-01

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

  5. Prostate cancer - treatment

    MedlinePlus

    ... well. Proton therapy is another kind of radiation therapy used to treat prostate cancer. Proton beams target the tumor precisely, so there is less damage to the surrounding tissue. This therapy is not widely accepted or used. Prostate Brachytherapy ...

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. Tocotrienols and Prostate Cancer

    DTIC Science & Technology

    2005-09-01

    factors [1-3]. Some evidence supports the protective effects of tomato products ( lycopene ), soy products (isoflavonoids) and fruits. Secondary...tocopherols and tocotrienols, have variable growth inhibitory effects on both types of prostate cancer cell line models. The gamma isoforms are more... effective than the alpha isoforms and the tocotrienols are more effective than the tocopherols. This study further showed that the vitamin E-mediated

  13. 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

  14. 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 ...

  15. 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

  16. 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

  17. Regulation of the Prostate Cancer Tumor Microenvironment

    DTIC Science & Technology

    2014-04-01

    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...prostate cancer glandular architecture formed (Figure 10). Figure 10. Subcutanous TRAMP Model to Recapitulate Prostate Cancer. TRAMP C2 cells...specifically modulate the TLR signaling pathway in prostate epithelium , stroma, and immune system. To parse out the role of TLR signaling in

  18. 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

  19. Screening for Prostate Cancer

    MedlinePlus

    ... for prostate cancer. It concluded that the expected harms of PSA screening are greater than the potential ... exam or other screening tests. Potential Benefits and Harms The main goal of a cancer screening test ...

  20. 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 ...

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. Sanguinarine: A Novel Agent Against Prostate Cancer

    DTIC Science & Technology

    2008-01-01

    surgical approaches have not been successful in the management of prostate cancer (CaP). Natural plant - based products have shown promise as anticancer...or treatment of prostate cancer . Several studies have shown that plant -derived alkaloids possess remarkable anticancer effects. Sanguinarine, an...Preclinical evaluation of plant alkaloid sanguinarine against prostate cancer development in a nude mice xenograft model. Proc Amer Assoc Cancer

  8. 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.

  9. 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.

  10. 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

  11. 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 ...

  12. 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.

  13. 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.

  14. 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

  15. Imaging Prostate Cancer with Positron Emission Tomography

    DTIC Science & Technology

    2014-07-01

    AD_________________ Award Number: W81XWH-13-1-0125 TITLE: Imaging Prostate Cancer with Positron Emission Tomography...ABOVE ADDRESS. 1. REPORT DATE 2014 2. REPORT TYPE Annual 3. DATES COVERED 01 Sept 2013-31 Aug 2014 4. TITLE AND SUBTITLE Imaging Prostate Cancer ...proposal is to develop peptide based radiopharmaceuticals and evaluate them as PET imaging agents in preclinical animal models of prostate cancer

  16. Prostate Cancer Disparities in an Incarcerated Community

    DTIC Science & Technology

    2012-09-01

    Florida Department of Corrections (FDOC) as a model for elucidating the genetic, epigenetic , and socio-environmental etiologies of prostate cancer . 9 | P...TITLE: Prostate Cancer Disparities in an Incarcerated Community PRINCIPAL INVESTIGATOR: Meghan E. Borysova, Ph.D...1 Sep 2011 - 31 Aug 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Prostate Cancer Disparities in an Incarcerated Community 5b. GRANT NUMBER

  17. Learning about Prostate Cancer

    MedlinePlus

    ... Gene Mapped To X Chromosome 1998 Researchers Link Gene to Hereditary Form of Prostate Cancer 2002 Get Email Updates Advancing human health through genomics research Privacy Copyright Contact Accessibility Plug-ins Site Map Staff Search FOIA Share Top

  18. 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 ...

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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.

  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. 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.

  6. 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

  7. 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.

  8. [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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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 ...

  14. 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

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

    DTIC Science & Technology

    2011-06-01

    the androgen axis, including those encoding enzymes of testosterone synthesis ( cytochrome P450c17) and conversion (steroid-5--reductase type 2...J., Gronberg, H., 2006. Germ- line genetic variation in the key androgen-regulating genes androgen receptor, cytochrome P450 , and steroid-5-alpha...4 Humanized Androgen Receptor Mice: A Genetic Model for Differential Response to Prostate Cancer Therapy INTRODUCTION Androgen

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

    DTIC Science & Technology

    2015-10-01

    Award Number: W81XWH-11-1-0639 TITLE: Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval PRINCIPAL...Clinical Trials and Drug Approval 5b. GRANT NUMBER PC100563 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Betty Diamond 5d. PROJECT NUMBER Ethan Basch...meet regulatory requirements for drug approval and labeling. The primary aim of this award is to conduct an observational longitudinal study in men

  17. 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

  18. 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

  19. Sanguinarine: A Novel Agent Against Prostate Cancer

    DTIC Science & Technology

    2007-02-01

    The traditional therapeutic and surgical approaches have not been successful in the management of prostate cancer (CaP). Natural plant - based...Natural plant -based products have shown promise as anticancer agents. Ideally, the anti- cancer drugs should specifically target the neoplastic cells... plant alkaloid sanguinarine against prostate cancer development in a nude mice xenograft model. Proc Amer Assoc Cancer Res 46: 1012-1013, 2005. 3

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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 ...

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. Expectant Management (Watchful Waiting) and Active Surveillance for Prostate Cancer

    MedlinePlus

    ... Prostate Cancer Watchful Waiting or Active Surveillance for Prostate Cancer Because prostate cancer often grows very slowly, some ... Away or Comes Back After Treatment More In Prostate Cancer About Prostate Cancer Causes, Risk Factors, and Prevention ...

  11. What Are the Key Statistics for Prostate Cancer?

    MedlinePlus

    ... Cancer Research? Prostate Cancer About Prostate Cancer Key Statistics for Prostate Cancer How common is prostate cancer? ... at some point are still alive today. For statistics related to survival, see Survival Rates for Prostate ...

  12. Vitamin E and Prostate Cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  13. 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.

  14. 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.

  15. [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.

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

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

    DTIC Science & Technology

    2011-02-01

    Palanisamy N, Chinnaiyan AM. 2009. Induced chromosomal proximity and gene fusions in prostate cancer. Science 326: 1230. Marker PC, Donjacour AA, Dahiya R...Identification of a new prostate cancer susceptibility locus on chromosome 8q24. Nat Genet 41: 1055–1057. Yu X, Wang Y , Jiang M, Bierie B, Roy-Burman...poorly differentiated cancer phenotype in each of the tumor-prone (tamoxifen-induced) mice. These tumors express CK8, a luminal cell marker , in the

  8. 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.

  9. 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

  10. 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

  11. 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].

  12. Protease Profiling in Prostate Cancer

    DTIC Science & Technology

    2004-05-01

    acid synthase, which contains a serine hydrolase domain. We identified a lead inhibitor of this domain of fatty acid synthase, called Orlistat, which...SUBJECT TERMS 15. NUMBER OF PAGES Prostate cancer, tumor biology, protease, proteomics, transgenic, 20 animal model, fatty acid synthase, orlistat 16...the enzymes we identified is fatty acid synthase. Fatty acid synthase is the sole enzyme responsible for the cellular synthesis of fatty acids . This

  13. 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

  14. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  16. 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.

  17. Prostate Cancer Prevention

    MedlinePlus

    ... prostate. The prostate is a gland in the male reproductive system . The prostate is just below the bladder (the ... part of the semen . Enlarge Anatomy of the male reproductive and urinary systems, showing the prostate, testicles, bladder, and other organs. ...

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

    DTIC Science & Technology

    2009-02-01

    PD0325901 effectively inhibited their target pathways when used individually or in com- bination, upregulation of Bim expression was most marked when the...that PTEN expression was mark - edly reduced with high frequency (59% cases) during prostate can- cer progression, as determined by comparing BPH, PIN...al. 2002. Immunohistochemical dem- onstration of phospho-Akt in high Gleason grade prostate cancer. Clin. Cancer Res. 8:1168–1171. 9. McMenamin , M.E

  19. Genomic Rearrangements in Prostate Cancer

    PubMed Central

    Barbieri, Christopher E.; Rubin, Mark A.

    2014-01-01

    Purpose of review Genomic instability is a fundamental feature of human cancer, leading to the activation of oncogenes and inactivation of tumor suppressors. In prostate cancer, structural genomic rearrangements, resulting in gene fusions, amplifications and deletions, are a critical mechanism effecting these alterations. Here we review recent literature regarding the importance of genomic rearrangements in the pathogenesis of prostate cancer and the potential impact on patient care. Recent findings Next generation sequencing has revealed a striking abundance, complexity, and heterogeneity of genomic rearrangements in prostate cancer. These recent studies have nominated a number of processes in predisposing prostate cancer to genomic rearrangements, including androgen-induced transcription. Summary Structural rearrangements are the critical mechanism resulting in the characteristic genomic changes associated with prostate cancer pathogenesis and progression. Future studies will determine if the impact of these events on tumor phenotypes can be translated to clinical utility for patient prognosis and choices of management strategies. PMID:25393273

  20. 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

  1. 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

  2. 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

  3. 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...

  4. 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 ...

  5. 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.

  6. 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

  7. 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

    2017-02-02

    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 2016. © 2017 American Cancer Society.

  8. 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...cholecystokinin responses in men fed barley pasta enriched with ß- glucan . American Journal of Clinical Nutrition 69:55-63. 21. 1999 Tinker LF, Parks EJ, Behr

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

    DTIC Science & Technology

    2012-07-01

    Chicago , IL) and NCSS (Kaysville, UT) software. Data is expressed as mean and stan- dard error of the mean (SE) unless otherwise specified and p values...Serum interleukin 6 as a prognostic factor in patients with prostate cancer. Clin Cancer Res 2000;6:2702–6. 84 [83] George DJ, Halabi S, Shepard

  10. Stages of Prostate Cancer

    MedlinePlus

    ... prostate. The prostate is a gland in the male reproductive system . It lies just below the bladder (the organ ... part of the semen . Enlarge Anatomy of the male reproductive and urinary systems, showing the prostate, testicles, bladder, and other organs. ...

  11. Prostate Cancer Screening

    MedlinePlus

    ... prostate. The prostate is a gland in the male reproductive system located just below the bladder (the organ that ... up part of semen . Enlarge Anatomy of the male reproductive and urinary systems, showing the prostate, testicles, bladder, and other organs. ...

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Polyphenols and Prostate Cancer Chemoprevention

    DTIC Science & Technology

    2005-03-01

    prostate chemoprevention are the soy isoflavone, genistein, and the tea catechin , (-)- epigallocatechin-3-gallate (EGCG). Another polyphenol that has...diet high in soy products have reduced incidence of clinically manifested prostate cancers. Likewise, Asians have a long history of drinking tea

  2. 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

  3. 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.

  4. The Prostate Cancer Biorepository Network (PCBN)

    DTIC Science & Technology

    2015-10-01

    and RNA ) from prostate cancer patients. These specimens are linked to clinical and outcome data and supported by an informatics infrastructure. In...models, manufactured and provided TMAs, and derived RNA and DNA where required. In addition, we have provided material to conduct biospecimen science...extensive collection of blood (serum, plasma, and buffy coat), prostatectomy tissues (frozen), and derived specimens (DNA and RNA ) from prostate

  5. Genetics Home Reference: prostate cancer

    MedlinePlus

    ... genes. Others act as tumor suppressors through different pathways. Changes in these genes probably make only a small contribution to overall prostate cancer risk. However, researchers suspect that the combined influence ...

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

    Oncogenic Pathway in Castration Resistance and Chemoresistance of Prostate Cancer 3 Annual Progress Report W81XWH-13-1-0162 Using a Novel...Transgenic Mouse Model to Study c-Myc Oncogenic Pathway in Castration Resistance and Chemoresistance of Prostate Cancer Feng Yang, Ph.D. Department of...AWARD NUMBER: W81XWH-13-1-0162 TITLE: Using a Novel Transgenic Mouse Model to Study c-Myc Oncogenic Pathway in Castration Resistance and

  16. Parameter estimation and optimal scheduling algorithm for a mathematical model of intermittent androgen suppression therapy for prostate cancer

    NASA Astrophysics Data System (ADS)

    Guo, Qian; Lu, Zhichang; Hirata, Yoshito; Aihara, Kazuyuki

    2013-12-01

    We propose an algorithm based on cross-entropy to determine parameters of a piecewise linear model, which describes intermittent androgen suppression therapy for prostate cancer. By comparing with clinical data, the parameter estimation for the switched system shows good fitting accuracy and efficiency. We further optimize switching time points for the piecewise linear model to obtain a feasible therapeutic schedule. The simulation results of therapeutic effect are superior to those of previous strategy.

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. What Tests Can Detect Prostate Cancer?

    MedlinePlus

    ... Prevention and Early Detection What Tests Can Detect Prostate Cancer Early? The tests discussed below are used to ... also found in the blood. Most men without prostate cancer have PSA levels under 4 nanograms per milliliter ( ...

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.…

  15. Microtubule Control of Metabolism in Prostate Cancer

    DTIC Science & Technology

    2013-06-01

    Prostate Cancer PRINCIPAL INVESTIGATOR: Lynne Cassimeris CONTRACTING ORGANIZATION...Microtubule Control of Metabolism in Prostate Cancer 5b. GRANT NUMBER W81XWH-12-1-0071 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...SUPPLEMENTARY NOTES 14. ABSTRACT The current standard chemotherapy treatment for metastatic castrate-resistant prostate cancer is the microtubule

  16. Microtubule Control of Metabolism in Prostate Cancer

    DTIC Science & Technology

    2013-11-01

    Prostate Cancer PRINCIPAL INVESTIGATOR: Lynne Cassimeris CONTRACTING ORGANIZATION: Lehigh University Bethlehem, PA 18015-3008 REPORT...Control of Metabolism in Prostate Cancer Dr. Lynne Cassimeris lc07@lehigh.edu Lehigh University 526 Brodhead Avenue Bethlehem, PA 18015-3008 U.S...tested whether metabolic inhibitors, metformin or 2-deoxy-glucose, function synergistically with docetaxel to block prostate cancer cell proliferation

  17. Reduction of Racial Disparities in Prostate Cancer

    DTIC Science & Technology

    2008-12-01

    JF, Levine AC. Inhibition of cyclooxygenase-2 suppresses angiogenesis and the growth of prostate cancer in vivo. J Urol 2000:164:820-5 10. Mahmud...Tzivony Y, Flescher E. Contrasting effects of aspirin on prostate cancer cells: suppression of proliferation and induction of drug resistance...TITLE: Reduction of Racial Disparities in Prostate Cancer PRINCIPAL INVESTIGATOR: Nicholas Daniels, MD MPH, Principal Investigator

  18. 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

  19. 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

  20. 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.

  1. The Relationship between Statins and Prostate Cancer Prevention

    DTIC Science & Technology

    2011-09-01

    In 2011, it is estimated that 240,890 men will be diagnosed with prostate cancer and 33,720 men will die from prostate cancer. Few prevention ...strategies for prostate cancer exist. HMG-CoA reductase inhibitors, statins, may prevent prostate cancer incidence and progression. We previously...prostate cancer in the Physicians’ Health Study and Early Stage Prostate Cancer Cohort study. Prostate cancer is commonly diagnosed and prevention

  2. 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.

  3. Mechanisms of Chinese Red Yeast Rice Inhibition of Prostate Cancer Growth

    DTIC Science & Technology

    2009-10-01

    14. ABSTRACT Prostate cancer is the second leading cause of cancer deaths in men in the United States. Early prostate cancer is androgen -dependent...rice vs lovas tatin effects on prostate cancer cells with and wit hout androgen rec eptor overexpression) (This paper is attached in appendix...Based on the in vitro study, androgen -dependent and –independent prostate cancer xenograft model was set up and the in vivo xenograft study as a functi

  4. 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.

  5. 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.

  6. 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

  7. Targeting Prostate Cancer with Multifunctional Nanoparticles

    DTIC Science & Technology

    2015-10-01

    4 Fig 1. Characterization of three prostate cancer cell lines by western blot. COXIV is used as a loading control...characterize our three prostate cancer cell lines , LNCaP, DU145 and PC3, which are being used in this project. We showed that prostate specific antigen...PSA) is expressed in the LNCaP cells, but absent in the DU145 cells whereas AMACR (P504S) is expressed in all prostate cancer cell lines (Fig 1

  8. 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

  9. 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

  10. 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

  11. 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

  12. Molecular Imaging with Quantum Dots Probing EMT and Prostate Cancer Metastasis in Live Animals

    DTIC Science & Technology

    2006-10-01

    model for prostate cancer . Lab Invest 1998;78(6):i–xv. 9. Greenberg NM. Androgens and growth factors in prostate cancer : A transgenic perspective...16. Zhau HY, Chang SM, Chen BQ, Wang Y, Zhang H, Kao C, Sang QA, Pathak SJ, Chung LW. Androgen -repressed phenotype in human prostate cancer . Proc Natl...CWR22: Androgen -dependent xenograft model derived from a primary human prostatic carcinoma. Cancer Res 1994;54(23): 6049–6052. 18. Corey E, Quinn JE

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  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. 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

  12. Prostate Cancer Research Training Program

    DTIC Science & Technology

    2014-05-01

    setting of cancer. Current efforts are focused on selecting RNA aptamers to receptors expressed on the surface of target cells with...institutions. A major project in the lab is targeted therapy of prostate cancer using PSMA-guided aptamers . Prabhat Goswami, PhD; Professor...participate. The Schultz lab also works to identify key cell-surface receptor residues as targets for novel peptide- and aptamer -based receptor

  13. 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.

  14. 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

  15. 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 ...

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. [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.

  7. 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.

  8. 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

  9. 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

  10. Targeting Discoidin Domain Receptors in Prostate Cancer

    DTIC Science & Technology

    2016-08-01

    1 AWARD NUMBER: W81XWH-15-1-0226 TITLE: Targeting Discoidin Domain Receptors in Prostate Cancer PRINCIPAL INVESTIGATOR: Dr. Rafael Fridman...4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-15-1-0226 Targeting Discoidin Domain Receptors in Prostate Cancer 5b. GRANT NUMBER W81XWH-15...DDRs in prostate cancer . During the first funding period, we conducted immunohistochemical studies by staining a 200 case Grade/Stage tissue

  11. Multifunctional Nanotherapeutic System for Advanced Prostate Cancer

    DTIC Science & Technology

    2013-10-01

    therapy for drug resistant prostate cancer cells. In addition the findings from this study can be extended to the combinatorial therapy involving...AD_________________ Award Number: W81XWH-11-1-0571 TITLE: “Multifunctional Nanotherapeutic System for Advanced Prostate Cancer ...29September2013 4. TITLE AND SUBTITLE Multifunctional Nanotherapeutic System for Advanced Prostate Cancer 5a. CONTRACT NUMBER W81XWH-11-1-0571 5b

  12. 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.

  13. 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

  14. 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

  15. Radiation Induced Immune Response in Prostate Cancer

    DTIC Science & Technology

    2014-12-01

    trials of antibodies to TIP-1 in patients receiving radiotherapy for radiation. Publications, Abstracts, and Presentations none Inventions...therapy. Because radiotherapy is a primary mode of treatment of both localized prostate cancer and metastatic prostate cancer. These antigens are...antigens that are specifically over- expressed in cancer resulting in too few molecular targets and small percentages of patients who can be treated

  16. 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.

  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. 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

  19. 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.

  20. 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

  1. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

    DTIC Science & Technology

    2014-09-01

    FAS activity in prostatectomy samples, intraprostatic lipid as measured by MRSI and prostate tumor aggressiveness. 3) To quantify key metabolic ...intermediates involved in lipid metabolism , mitochondrial function, inflammation, and apoptosis in the prostatectomy samples. 15. SUBJECT TERMS : none...vivo intraprostatic fat as measured by 1H MRSI, metabolic signatures of lipid oxidation and metabolism , and prostate cancer aggressiveness, our

  2. 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.

  3. 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).

  4. Olaparib With or Without Cediranib in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

    ClinicalTrials.gov

    2017-04-04

    Castration-Resistant Prostate Carcinoma; Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma With Focal Neuroendocrine Differentiation; Prostate Carcinoma Metastatic in the Bone; Prostate Small Cell Carcinoma; Stage IV Prostate Adenocarcinoma

  5. 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

  6. [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.

  7. 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.

  8. 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

  9. Solidago Virgaurea for Prostate Cancer Therapy

    DTIC Science & Technology

    2009-04-01

    Huang, H.S. Luo, J.P. Yu, J.J. Meier, H. Schrader, A. Bastian, W.E. Schmidt, F. Schmitz, The effects of acetylsalicylic acid on proliferation, apoptosis...agent by targeting a specific gene or pathway with well-defined clinical rationale is needed. We chose a target called Fatty acid synthase (FAS...virgaurea on tumorigenesis in an animal model. 15. SUBJECT TERMS Prostate cancer, Fatty acid synthase, Solidago virgaurea, 16. SECURITY

  10. 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...cleaved at the cell surface by a protease that is inhibited by metal ion chelators. This work was done in a human embryonic kidney cell line. The goal

  11. 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

  12. 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

  13. Vaccine Immunotherapy for Prostate Cancer

    DTIC Science & Technology

    2006-07-01

    comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE...growth of androgen-dependent cancer cells, and result in clinical tumor control . After a median time of 2 years, patients progress into a clinical...calculogenesis. Finally, Bischoff and Goerttler (38) used Gelfoam in human prostate therapeutic embolization with success. Our laboratory, in collaboration

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. Prevention and Early Detection of Prostate Cancer

    PubMed Central

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

    2014-01-01

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

  1. 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

  2. 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

  3. 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.

  4. 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

    basis for studies on the differences in reprogramming of skin fibroblasts and their differentiation into prostate epithelial cells and susceptibility... transdifferentiation : implications for novel therapeutic strategies. American Journal of Stem Cells 2: 52-61. Funding applied for- Fiscal Year 2013

  5. 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

  6. [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.

  7. 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.

  8. 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.

  9. Circadian Genes and Risk for Prostate Cancer

    DTIC Science & Technology

    2009-03-01

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

  10. Circadian Genes and Risk for Prostate Cancer

    DTIC Science & Technology

    2011-09-01

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

  11. Validation of Biomarkers for Prostate Cancer Prognosis

    DTIC Science & Technology

    2014-10-01

    developing cancer diagnostic biomarkers. Genome Research 22: 183-187, 2012. Sarah Hawley, Ladan Fazli , Jesse K. McKenney, Jeff Simko, Dean Troyer, Marlo...MUC1 in human prostate cancers. Prostate 74: 1059-1067, 2014. Troyer D, Jamaspishvili T, Wei W, Feng Z, Good J, Hawley S, Fazli L, McKenney J

  12. A history of prostate cancer treatment

    PubMed Central

    Denmeade, Samuel R.; Isaacs, John T.

    2014-01-01

    The increased incidence of prostate cancer has led to remarkable changes in diagnosis and treatment over the past century. What were the first ways in which prostate cancer was treated, and how did these evolve into the variety of therapeutic strategies from which patients have to choose today? PMID:12044015

  13. Prostate Cancer Genetics in African Americans

    DTIC Science & Technology

    2014-09-01

    receiving appropriate education, genetic counseling , and/or referral. During each interview the research coordinator identifies at risk family members...AD_________________ Award Number: W81XWH-11-1-0566 TITLE: Prostate Cancer Genetics in African...ADDRESS. 1. REPORT DATE 2. REPORT TYPE Annual 3. DATES COVERED 15 Aug 2013 – 14 Aug 2014 4. TITLE AND SUBTITLE Prostate Cancer Genetics in

  14. Prostate Cancer Genetics in African Americans

    DTIC Science & Technology

    2015-11-01

    AWARD NUMBER: W81XWH-11-1-0566 TITLE: Prostate Cancer Genetics in African Americans PRINCIPAL INVESTIGATOR: Henry T. Lynch, MD CONTRACTING...W81XWH-11-1-0566 November 2015 Final 15Aug2011 - 14Aug2015 Prostate Cancer Genetics in African Americans Henry T. Lynch Nothing listed 36

  15. Erythrocyte Fatty Acids and Prostate Cancer Risk: A comparison of methods

    PubMed Central

    Shannon, J; O'Malley, J; Mori, M; Garzotto, M; Palma, AJ; King, IB

    2010-01-01

    Summary The role of fatty acids (FA) in prostate carcinogenesis is unclear. Interest in the interrelationship among different types of FA has resulted in new analytic approaches to FA and their role in cancer development. We evaluated the association between erythrocyte FA and prostate cancer in 127 prostate cancer patients and 183 screen negative controls. We present three approaches to analyses of the FA and prostate cancer association; 1) individual or common groups of FA, 2) biologically meaningful FA ratios and 3) principal components analysis. Monounsaturated FA and the alpha-linolenic:eicosapentaenoic ratio were associated with reduced risk of prostate cancer. However, Factor 1, which was strongly correlated with some long chain saturated FA, was associated with an increased risk of prostate cancer. We provide an example of modeling FA and their interrelationships on the risk of prostate cancer. Comparing three approaches suggests the importance of considering the impact of the entire fatty acid profile in disease prevention. PMID:20630734

  16. Detection of DNA viruses in prostate cancer

    PubMed Central

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

    2016-01-01

    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. PMID:27121729

  17. Castration Induced Neuroendocrine Mediated Progression of Prostate Cancer

    DTIC Science & Technology

    2007-09-01

    androgen -insensitive prostate cancer patients based upon our work. 15. SUBJECT TERMS Prostate Cancer , Neuroendocrine, Progression...two androgen - ines PC-3 and DU-145 by examining the status of publication. a Src kinase inhibitor AZ independent prostate cancer cell l...differentiation in prostate cancer . AR activation. Together with our studies in the chimeric growth of androgen -sensitive and androgen -insensitive cells,

  18. Prostate Cancer Genetics in African Americans

    DTIC Science & Technology

    2013-09-01

    grant from the U.S. Department of Defense to study the role heredity plays in prostate cancer among African Americans. "Prostate cancer is the...visit our website at: www.creighton.edu. Creighton gets grant to study heredity -cancer link - Houston Chronicle Coogle offers Google Offers Deals on...traffic Nahan & world Politics Health News bizarre Deaths Hurncanes Creighton gets grant to study heredity -cancer link Published 04 :40a.m., Monday

  19. Bone-targeting agents in prostate cancer

    PubMed Central

    Suzman, Daniel L.; Boikos, Sosipatros A.; Carducci, Michael A.

    2014-01-01

    Bone metastases are present in the vast majority of men with advanced prostate cancer, representing the main cause for morbidity and mortality. Recurrent or metastatic disease is managed initially with androgen deprivation but the majority of the patients eventually will progress to castration-resistant prostate cancer, with patients developing bone metastases in most of the cases. Survival and growth of the metastatic prostate cancer cells is dependent on a complex microenvironment (onco-niche) that includes the osteoblasts, the osteoclasts, the endothelium, and the stroma. This review summarizes agents that target the pathways involved in this complex interaction between prostate cancer and bone micro-environment and aim to transform lethal metastatic prostate cancer into a chronic disease. PMID:24398856

  20. A novel spontaneous model of epithelial-mesenchymal transition (EMT) using a primary prostate cancer derived cell line demonstrating distinct stem-like characteristics.

    PubMed

    Harner-Foreman, Naomi; Vadakekolathu, Jayakumar; Laversin, Stéphanie A; Mathieu, Morgan G; Reeder, Stephen; Pockley, A Graham; Rees, Robert C; Boocock, David J

    2017-01-17

    Cells acquire the invasive and migratory properties necessary for the invasion-metastasis cascade and the establishment of aggressive, metastatic disease by reactivating a latent embryonic programme: epithelial-to-mesenchymal transition (EMT). Herein, we report the development of a new, spontaneous model of EMT which involves four phenotypically distinct clones derived from a primary tumour-derived human prostate cancer cell line (OPCT-1), and its use to explore relationships between EMT and the generation of cancer stem cells (CSCs) in prostate cancer. Expression of epithelial (E-cadherin) and mesenchymal markers (vimentin, fibronectin) revealed that two of the four clones were incapable of spontaneously activating EMT, whereas the others contained large populations of EMT-derived, vimentin-positive cells having spindle-like morphology. One of the two EMT-positive clones exhibited aggressive and stem cell-like characteristics, whereas the other was non-aggressive and showed no stem cell phenotype. One of the two EMT-negative clones exhibited aggressive stem cell-like properties, whereas the other was the least aggressive of all clones. These findings demonstrate the existence of distinct, aggressive CSC-like populations in prostate cancer, but, importantly, that not all cells having a potential for EMT exhibit stem cell-like properties. This unique model can be used to further interrogate the biology of EMT in prostate cancer.

  1. A novel spontaneous model of epithelial-mesenchymal transition (EMT) using a primary prostate cancer derived cell line demonstrating distinct stem-like characteristics

    PubMed Central

    Harner-Foreman, Naomi; Vadakekolathu, Jayakumar; Laversin, Stéphanie A.; Mathieu, Morgan G.; Reeder, Stephen; Pockley, A. Graham; Rees, Robert C.; Boocock, David J.

    2017-01-01

    Cells acquire the invasive and migratory properties necessary for the invasion-metastasis cascade and the establishment of aggressive, metastatic disease by reactivating a latent embryonic programme: epithelial-to-mesenchymal transition (EMT). Herein, we report the development of a new, spontaneous model of EMT which involves four phenotypically distinct clones derived from a primary tumour-derived human prostate cancer cell line (OPCT-1), and its use to explore relationships between EMT and the generation of cancer stem cells (CSCs) in prostate cancer. Expression of epithelial (E-cadherin) and mesenchymal markers (vimentin, fibronectin) revealed that two of the four clones were incapable of spontaneously activating EMT, whereas the others contained large populations of EMT-derived, vimentin-positive cells having spindle-like morphology. One of the two EMT-positive clones exhibited aggressive and stem cell-like characteristics, whereas the other was non-aggressive and showed no stem cell phenotype. One of the two EMT-negative clones exhibited aggressive stem cell-like properties, whereas the other was the least aggressive of all clones. These findings demonstrate the existence of distinct, aggressive CSC-like populations in prostate cancer, but, importantly, that not all cells having a potential for EMT exhibit stem cell-like properties. This unique model can be used to further interrogate the biology of EMT in prostate cancer. PMID:28094783

  2. [Genome-wide association study(GWAS) and genetic risk of prostate cancer].

    PubMed

    Nakagawa, Hidewaki; Akamatsu, Shusuke; Takata, Ryo

    2016-01-01

    It is evident that genetic factors play critical roles in prostate cancer development. GWAS (genome-wide association studies) in multiple ethnic groups have been identifying more than 100 loci or genes which was significantly associated with prostate cancer susceptibility. They include several loci at 8q24, prostate-specific gene, inflammation gene, and metabolism-related genes. Risk prediction for prostate cancer by combining multiple SNPs is still primitive and not sufficiently accurate for clinical use, but this model could have a potential to affect clinical decision when it is applied to patients with gray-zone PSA or very high risk of prostate cancer.

  3. PSA and beyond: alternative prostate cancer biomarkers

    PubMed Central

    2016-01-01

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

  4. Endometase in Androgen-Repressed Human Prostate Cancer

    DTIC Science & Technology

    2005-03-01

    intraepithelial neoplasia from multiple patients were significantly higher than those in prostatitis, benign prostate hyperplasia, and normal prostate glandular...prostate cancer cell invasion. 3. We showed that the levels of MMP-26 protein in human prostate carcinomas from multiple patients were significantly...inhibitors of MMP-26 block prostate cancer invasion. We have showed that the levels of MMP-26 protein in human prostate carcinomas from multiple patients were

  5. Targeting cells of the myeloid lineage attenuates pain and disease progression in a prostate model of bone cancer.

    PubMed

    Thompson, Michelle L; Jimenez-Andrade, Juan M; Chartier, Stephane; Tsai, James; Burton, Elizabeth A; Habets, Gaston; Lin, Paul S; West, Brian L; Mantyh, Patrick W

    2015-09-01

    Tumor cells frequently metastasize to bone where they can generate cancer-induced bone pain (CIBP) that can be difficult to fully control using available therapies. Here, we explored whether PLX3397, a high-affinity small molecular antagonist that binds to and inhibits phosphorylation of colony-stimulating factor-1 receptor, the tyrosine-protein kinase c-Kit, and the FMS-like tyrosine kinase 3, can reduce CIBP. These 3 targets all regulate the proliferation and function of a subset of the myeloid cells including macrophages, osteoclasts, and mast cells. Preliminary experiments show that PLX3397 attenuated inflammatory pain after formalin injection into the hind paw of the rat. As there is an inflammatory component in CIBP, involving macrophages and osteoclasts, the effect of PLX3397 was explored in a prostate model of CIBP where skeletal pain, cancer cell proliferation, tumor metastasis, and bone remodeling could be monitored in the same animal. Administration of PLX3397 was initiated on day 14 after prostate cancer cell injection when the tumor was well established, and tumor-induced bone remodeling was first evident. Over the next 6 weeks, sustained administration of PLX3397 attenuated CIBP behaviors by approximately 50% and was equally efficacious in reducing tumor cell growth, formation of new tumor colonies in bone, and pathological tumor-induced bone remodeling. Developing a better understanding of potential effects that analgesic therapies have on the tumor itself may allow the development of therapies that not only better control the pain but also positively impact disease progression and overall survival in patients with bone cancer.

  6. Selenite Treatment Inhibits LAPC-4 Tumor Growth and Prostate-Specific Antigen Secretion in a Xenograft Model of Human Prostate Cancer

    SciTech Connect

    Bhattacharyya, Rumi S.; Husbeck, Bryan; Feldman, David; Knox, Susan J.

    2008-11-01

    Purpose: Selenium compounds have known chemopreventive effects on prostate cancer. However selenite, an inorganic form of selenium, has not been extensively studied as a treatment option for prostate cancer. Our previous studies have demonstrated the inhibition of androgen receptor expression and androgen stimulated prostate-specific antigen (PSA) expression by selenite in human prostate cancer cell lines. In this study, we investigated the in vivo effects of selenite as a therapy to treat mice with established LAPC-4 tumors. Methods and Materials: Male mice harboring androgen-dependent LAPC-4 xenograft tumors were treated with selenite (2 mg/kg intraperitoneally three times per week) or vehicle for 42 days. In addition, androgen-independent LAPC-4 xenograft tumors were generated in female mice over 4 to 6 months. Once established, androgen-independent LAPC-4 tumor fragments were passaged into female mice and were treated with selenite or vehicle for 42 days. Changes in tumor volume and serum PSA levels were assessed. Results: Selenite significantly decreased androgen-dependent LAPC-4 tumor growth in male mice over 42 days (p < 0.001). Relative tumor volume was decreased by 41% in selenite-treated animals compared with vehicle-treated animals. The inhibition of LAPC-4 tumor growth corresponded to a marked decrease in serum PSA levels (p < 0.01). In the androgen-independent LAPC-4 tumors in female mice, selenite treatment decreased tumor volume by 58% after 42 days of treatment (p < 0.001). Conclusions: These results suggest that selenite may have potential as a novel therapeutic agent to treat both androgen-dependent and androgen-independent prostate cancer.

  7. Phase of care prevalence for prostate cancer in New South Wales, Australia: A population-based modelling study

    PubMed Central

    Luo, Qingwei; Smith, David P.; Clements, Mark S.; Patel, Manish I.; O’Connell, Dianne L.

    2017-01-01

    Objective To develop a method for estimating the future numbers of prostate cancer survivors requiring different levels of care. Design, setting and participants Analysis of population-based cancer registry data for prostate cancer cases (aged 18–84 years) diagnosed in 1996–2007, and a linked dataset with hospital admission data for men with prostate cancer diagnosed during 2005–2007 in New South Wales (NSW), Australia. Methods Cancer registry data (1996–2007) were used to project complete prostate cancer prevalence in NSW, Australia for 2008–2017, and treatment information from hospital records (2005–2007) was used to estimate the inpatient care needs during the first year after diagnosis. The projected complete prevalence was divided into care needs-based groups. We first divided the cohort into two groups based on patient’s age (<75 and 75–84 years). The younger cohort was further divided into initial care and monitoring phases. Cause of death data were used as a proxy for patients requiring last year of life prostate cancer care. Finally, episode data were used to estimate the future number of cases with metastatic progression. Results Of the estimated total of 60,910 men with a previous diagnosis of prostate cancer in 2017, the largest groups will be older patients (52.0%) and younger men who require monitoring (42.5%). If current treatment patterns continue, in the first year post-diagnosis 41% (1380) of patients (<75 years) will have a radical prostatectomy, and 52.6% (1752) will be likely to have either active surveillance, external beam radiotherapy or androgen deprivation therapy. About 3% will require care for subsequent metastases, and 1288 men with prostate cancer are likely to die from the disease in 2017. Conclusions This method extends the application of routinely collected population-based data, and can contribute much to the knowledge of the number of men with prostate cancer and their health care requirements. This could be of

  8. Identification of Androgen Receptor and Beta-Catenin Target Genes in Prostate and Prostate Cancer

    DTIC Science & Technology

    2013-10-01

    Transdisciplinary Research in Epigenetics and Cancer Journal Clubs and Transdisciplinary Science Meetings, biweekly and monthly 3. To gain expertise...Target Genes in Prostate and Prostate Cancer PRINCIPAL INVESTIGATOR: Laura Lamb CONTRACTING ORGANIZATION: Washington University...TITLE AND SUBTITLE Identification of Androgen Receptor and Beta-Catenin Target Genes in Prostate and Prostate Cancer 5a. CONTRACT NUMBER Genes in

  9. Defining the radiobiology of prostate cancer progression: An important question in translational prostate cancer research

    PubMed Central

    Vourganti, Srinivas; Donaldson, Jeffrey; Johnson, Linda; Turkbey, Baris; Bratslavsky, Gennady; Kotula, Leszek

    2015-01-01

    Prostate cancer is one of the most common malignancies affecting men worldwide. High mortality rates from advanced and metastatic prostate cancer in the United States are contrasted by a relatively indolent course in the majority of cases. This gives hope for finding methods that could direct personalized diagnostic, preventative, and treatment approaches to patients with prostate cancer. Recent advances in multiparametric magnetic resonance imaging (MP-MRI) offer a noninvasive diagnostic intervention which allows correlation of prostate tumor image characteristics with underlying biologic evidence of tumor progression. The power of MP-MRI includes examination of both local invasion and nodal disease and might overcome the challenges of analyzing the multifocal nature of prostate cancer. Future directions include a careful analysis of the genomic signature of individual prostatic lesions utilizing image-guided biopsies. This review examines the diagnostic potential of MRI in prostate cancer. PMID:24879423

  10. Diagnosis of prostate cancer via nanotechnological approach.

    PubMed

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

    2015-01-01

    Prostate cancer is one of the leading causes of cancer-related deaths among the Caucasian adult males in Europe and the USA. Currently available diagnostic strategies for patients with prostate cancer are invasive and unpleasant and have poor accuracy. Many patients have been overly or underly treated resulting in a controversy regarding the reliability of current conventional diagnostic approaches. This review discusses the state-of-the-art research in the development of novel noninvasive prostate cancer diagnostics using nanotechnology coupled with suggested diagnostic strategies for their clinical implication.

  11. Sci—Thur AM: YIS - 02: Radiogenomic Modeling of Normal Tissue Toxicities in Prostate Cancer Patients Receiving Hypofractionated Radiotherapy

    SciTech Connect

    Coates, J; Jeyaseelan, K; Ybarra, N; David, M; Faria, S; Souhami, L; Cury, F; Duclos, M; El Naqa, I

    2014-08-15

    Inter-patient radiation sensitivity variability has recently been shown to have a genetic component. This genetic component may play a key role in explaining the fluctuating rates of radiation-induced toxicities (RITs). Single nucleotide polymorphisms (SNPs) have thus far yielded inconsistent results in delineating RITs while copy number variations (CNVs) have not yet been investigated for such purposes. We explore a radiogenomic modeling approach to investigate the association of CNVs and SNPs, along with clinical and dosimetric variables, in radiation induced rectal bleeding (RB) and erectile dysfunction (ED) in prostate cancer patients treated with curative hypofractionated irradiation. A cohort of 62 prostate cancer patients who underwent hypofractionated radiotherapy (66 Gy in 22 fractions) between 2002 to 2010 were retrospectively genotyped for CNV and SNP rs5489 in the xrcc1 DNA repair gene. Late toxicity rates for RB grade 2 and 3 and grade 3 alone were 29.0% and 12.9%, respectively. ED toxicity was found to be 62.9%. Radiogenomic model performance was evaluated using receiver operating characteristic area under the curve (AUC) and resampling by cross-validation. Binary variables were evaluated using Chi-squared contingency table analysis and multivariate models by Spearman's rank correlation coefficient (rs). Ten patients were found to have three copies of xrcc1 CNV (RB: χ{sup 2}=14.6, p<0.001 and ED: χ{sup 2}=4.88, p=0.0272) and twelve had heterozygous rs25489 SNP (RB: χ{sup 2}=0.278, p=0.599 and ED: χ{sup 2}=0.112, p=0.732). Radiogenomic modeling yielded significant, cross-validated NTCP models for RB (AUC=0.665) and ED (AUC=0.754). These results indicate that CNVs may be potential predictive biomarkers of both late ED and RB.

  12. SU-F-BRD-01: A Logistic Regression Model to Predict Objective Function Weights in Prostate Cancer IMRT

    SciTech Connect

    Boutilier, J; Chan, T; Lee, T; Craig, T; Sharpe, M

    2014-06-15

    Purpose: To develop a statistical model that predicts optimization objective function weights from patient geometry for intensity-modulation radiotherapy (IMRT) of prostate cancer. Methods: A previously developed inverse optimization method (IOM) is applied retrospectively to determine optimal weights for 51 treated patients. We use an overlap volume ratio (OVR) of bladder and rectum for different PTV expansions in order to quantify patient geometry in explanatory variables. Using the optimal weights as ground truth, we develop and train a logistic regression (LR) model to predict the rectum weight and thus the bladder weight. Post hoc, we fix the weights of the left femoral head, right femoral head, and an artificial structure that encourages conformity to the population average while normalizing the bladder and rectum weights accordingly. The population average of objective function weights is used for comparison. Results: The OVR at 0.7cm was found to be the most predictive of the rectum weights. The LR model performance is statistically significant when compared to the population average over a range of clinical metrics including bladder/rectum V53Gy, bladder/rectum V70Gy, and mean voxel dose to the bladder, rectum, CTV, and PTV. On average, the LR model predicted bladder and rectum weights that are both 63% closer to the optimal weights compared to the population average. The treatment plans resulting from the LR weights have, on average, a rectum V70Gy that is 35% closer to the clinical plan and a bladder V70Gy that is 43% closer. Similar results are seen for bladder V54Gy and rectum V54Gy. Conclusion: Statistical modelling from patient anatomy can be used to determine objective function weights in IMRT for prostate cancer. Our method allows the treatment planners to begin the personalization process from an informed starting point, which may lead to more consistent clinical plans and reduce overall planning time.

  13. Cooperativity Between Oncogenic PKC Epsilon and Pten Loss in Prostate Cancer Progression

    DTIC Science & Technology

    2015-10-01

    cooperate for the development of prostate cancer. We recapitulated these data using genetically engineered mouse models that were developed in our...one of the most common genetic alterations in human prostate cancer and PKCε overexpression is also found in most prostate tumors, we anticipate...from prostate epithelial cells isolated from Pten knock-out mice, and engineered to overexpress PKCε (CaP2-PKCε and CaP8-PKCε). Both cell lines behave

  14. Cytoprotective Mitochondrial Chaperone TRAP-1 As a Novel Molecular Target in Localized and Metastatic Prostate Cancer

    PubMed Central

    Leav, Irwin; Plescia, Janet; Goel, Hira Lal; Li, Jing; Jiang, Zhong; Cohen, Ronald J.; Languino, Lucia R.; Altieri, Dario C.

    2010-01-01

    Molecular chaperones of the heat shock protein-90 (Hsp90) family promote cell survival, but the molecular requirements of this pathway in tumor progression are not understood. Here, we show that a mitochondria-localized Hsp90 chaperone, tumor necrosis factor receptor-associated protein-1 (TRAP-1), is abundantly and ubiquitously expressed in human high-grade prostatic intraepithelial neoplasia, Gleason grades 3 through 5 prostatic adenocarcinomas, and metastatic prostate cancer, but largely undetectable in normal prostate or benign prostatic hyperplasia in vivo. Prostate lesions formed in genetic models of the disease, including the transgenic adenocarcinoma of the mouse prostate and mice carrying prostate-specific deletion of the phosphatase tensin homolog tumor suppressor (Ptenpc−/−), also exhibit high levels of TRAP-1. Expression of TRAP-1 in nontransformed prostatic epithelial BPH-1 cells inhibited cell death, whereas silencing of TRAP-1 in androgen-independent PC3 or DU145 prostate cancer cells by small interfering RNA enhanced apoptosis. Targeting TRAP-1 with a novel class of mitochondria-directed Hsp90 inhibitors, ie, Gamitrinibs, caused rapid and complete killing of androgen-dependent or -independent prostate cancer, but not BPH-1 cells, whereas reintroduction of TRAP-1 in BPH-1 cells conferred sensitivity to Gamitrinib-induced cell death. These data identify TRAP-1 as a novel mitochondrial survival factor differentially expressed in localized and metastatic prostate cancer compared with normal prostate. Targeting this pathway with Gamitrinibs could be explored as novel molecular therapy in patients with advanced prostate cancer. PMID:19948822

  15. Prostate cancer vaccines in clinical trials.

    PubMed

    Lubaroff, David M

    2012-07-01

    This review presents important information about the current state of the art for vaccine immunotherapy of prostate cancer. It includes important preclinical research for each of the important prostate cancer vaccines to have reached clinical trials. To date, the only prostate cancer vaccine that has completed Phase III trials and has been approved and licensed by the US FDA is Sipuleucel-T, which immunizes patients against the prostate-associated antigen prostatic acid phosphatase. The benefits and concerns associated with the vaccine are presented. A current Phase III trial is currently underway using the vaccinia-based prostate-specific antigen vaccine Prostvac-TRICOM. Other immunotherapeutic vaccines in trials include the Ad/prostate-specific antigen vaccine Ad5-prostate-specific antigen and the DNA/prostatic acid phosphatase vaccine. A cellular vaccine, GVAX, has been in clinical trials but has not seen continuous study. This review also delves into the multiple immune regulatory elements that must be overcome in order to obtain strong antitumor-associated antigen immune responses capable of effectively destroying prostate tumor cells.

  16. ETS fusion genes in prostate cancer.

    PubMed

    Gasi Tandefelt, Delila; Boormans, Joost; Hermans, Karin; Trapman, Jan

    2014-06-01

    Prostate cancer is very common in elderly men in developed countries. Unravelling the molecular and biological processes that contribute to tumor development and progressive growth, including its heterogeneity, is a challenging task. The fusion of the genes ERG and TMPRSS2 is the most frequent genomic alteration in prostate cancer. ERG is an oncogene that encodes a member of the family of ETS transcription factors. At lower frequency, other members of this gene family are also rearranged and overexpressed in prostate cancer. TMPRSS2 is an androgen-regulated gene that is preferentially expressed in the prostate. Most of the less frequent ETS fusion partners are also androgen-regulated and prostate-specific. During the last few years, novel concepts of the process of gene fusion have emerged, and initial experimental results explaining the function of the ETS genes ERG and ETV1 in prostate cancer have been published. In this review, we focus on the most relevant ETS gene fusions and summarize the current knowledge of the role of ETS transcription factors in prostate cancer. Finally, we discuss the clinical relevance of TMRPSS2-ERG and other ETS gene fusions in prostate cancer.

  17. Measuring the effects of fractionated radiation therapy in a 3D prostate cancer model system using SERS nanosensors.

    PubMed

    Camus, Victoria L; Stewart, Grant; Nailon, William H; McLaren, Duncan B; Campbell, Colin J

    2016-08-15

    Multicellular tumour spheroids (MTS) are three-dimensional cell cultures that possess their own microenvironments and provide a more meaningful model of tumour biology than monolayer cultures. As a result, MTS are becoming increasingly used as tumor models when measuring the efficiency of therapies. Monitoring the viability of live MTS is complicated by their 3D nature and conventional approaches such as fluorescence often require fixation and sectioning. In this paper we detail the use of Surface Enhanced Raman Spectroscopy (SERS) to measure the viability of MTS grown from prostate cancer (PC3) cells. Our results show that we can monitor loss of viability by measuring pH and redox potential in MTS and furthermore we demonstrate that SERS can be used to measure the effects of fractionation of a dose of radiotherapy in a way that has potential to inform treatment planning.

  18. Prostate cancer and the influence of dietary factors and supplements: a systematic review

    PubMed Central

    2014-01-01

    Background Prostate cancer is the second most common cause of cancer worldwide after lung cancer. There is increasing evidence that diet and lifestyle plays a crucial role in prostate cancer biology and tumourigenesis. Prostate cancer itself represents a good model of cancer in which to look for chemopreventive agents due to the high disease prevalence, slowly progressive nature, and long latency period. Dietary agents have gained considerable attention, often receiving much publicity in the media. Aim To review the key evidence available for potential chemopreventive nutrients. Methods The methodology for this review involved a PubMed search from 1990 to 2013 using the key-words “diet and prostate cancer”, “nutrition and prostate cancer”, “dietary factors and prostate cancer”, “prostate cancer epidemiology”, “prostate cancer prevention”, “prostate cancer progression”. Results Red meat, dietary fat and milk intake should be minimised as they appear to increase the risk of prostate cancer. Fruit and vegetables and polyphenols may be preventive in prostate cancer, but further studies are needed to draw more solid conclusions and to clarify their role in patients with an established diagnosis of prostate cancer. Selenium and vitamin supplements cannot be advocated for the prevention of prostate cancer and indeed higher doses may be associated with a worse prognosis. There is no specific evidence regarding benefits of probiotics or prebiotics in prostate cancer. Conclusions From the wealth of evidence available, many recommendations can be made although more randomised control trials are required. These need to be carefully designed due to the many confounding factors and heterogeneity of the population. PMID:24976856

  19. Prostate Cancer and Bone: The Elective Affinities

    PubMed Central

    2014-01-01

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

  20. Examination of the Role of DNA Methylation Changes in Prostate Cancer using the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) Model

    DTIC Science & Technology

    2010-03-01

    genotypes of Dnmt1 hypomorphic mice as expected (Figure 6A). In contrast, Dnmt3a and Dnmt3b displayed variable expression patterns, with no clear change in...for molecular analyses. To confirm specific knockdown of Dnmt1, I measured Dnmt1, Dnmt3a, and Dnmt3b mRNA and protein expressions in the prostates...points (Figure 9A). In contrast, Dnmt3a and Dnmt3b mRNA expression shows variability amongst the four genotypes, with the only significant change

  1. Examination of the Role of DNA Methylation Changes in Prostate Cancer using the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) Model

    DTIC Science & Technology

    2009-03-01

    and lymph node tissues. I next measured Dnmt1, Dnmt3a, and Dnmt3b mRNA expression, B1 repetitive element methylation, and global (5mdC) levels...tumor progression, we were unsure of how they may change in the TRAMP Dnmt1 Hypomorphic mice (1-3). Dnmt1, Dnmt3a, and Dnmt3b mRNA expression are...significantly decreased in R/+ and N/R mice compared to WT TRAMP mouse prostate tissue (Fig. 8d-f). Dnmt3a and Dnmt3b mRNA expression shows some

  2. Immunostimulatory early phenotype of tumor-associated macrophages does not predict tumor growth outcome in an HLA-DR mouse model of prostate cancer.

    PubMed

    Riabov, Vladimir; Kim, David; Chhina, Surmeet; Alexander, Richard B; Klyushnenkova, Elena N

    2015-07-01

    Tumor-associated macrophages (TAM) were shown to support the progression of many solid tumors. However, anti-tumor properties of TAM were also reported in several types of cancer. Here, we investigated the phenotype and functions of TAM in two transgenic mouse models of prostate cancer that display striking differences in tumor growth outcome. Mice expressing prostate-specific antigen (PSA) as a self-antigen specifically in prostate (PSAtg mice) rejected PSA-expressing transgenic adenocarcinoma of mouse prostate (TRAMP) tumors. However, the introduction of HLA-DRB1*1501 (DR2b) transgene presenting PSA-derived peptides in a MHC class II-restricted manner exacerbated the growth of TRAMP-PSA tumors in DR2bxPSA F 1 mice. Despite the difference in tumor growth outcome, tumors in both strains were equally and intensively infiltrated by macrophages on the first week after tumor challenge. TAM exhibited mixed M1/M2 polarization and simultaneously produced pro-inflammatory (TNFα, IL1β) and anti-inflammatory (IL10) cytokines. TAM from both mouse strains demonstrated antigen-presenting potential and pronounced immunostimulatory activity. Moreover, they equally induced apoptosis of tumor cells. In vivo depletion of macrophages in DR2bxPSA F 1 but not PSAtg mice aggravated tumor growth suggesting that macrophages more strongly contribute to anti-tumor immunity when specific presentation of PSA to CD4+ T cells is possible. In summary, we conclude that in the early stages of tumor progression, the phenotype and functional properties of TAM did not predict tumor growth outcome in two transgenic prostate cancer models. Furthermore, we demonstrated that during the initial stage of prostate cancer development, TAM have the potential to activate T cell immunity and mediate anti-tumor effects.

  3. Early Growth Inhibition Is Followed by Increased Metastatic Disease with Vitamin D (Calcitriol) Treatment in the TRAMP Model of Prostate Cancer

    PubMed Central

    Karasik, Ellen; Gillard, Bryan; Moser, Michael T.; Johnson, Candace S.; Trump, Donald L.; Foster, Barbara A.

    2014-01-01

    The active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 (calcitriol) has antiproliferative effects in non-aggressive prostate cancer, however, its effects in more aggressive model systems are still unclear. In these studies, effects of calcitriol and a less-calcemic vitamin D analog, QW-1624F2-2 (QW), were tested in vivo, using the aggressive autochthonous transgenic adenocarcinoma of mouse prostate (TRAMP) model. To study prevention of androgen-stimulated prostate cancer, vehicle, calcitriol (20 µg/kg), or QW (50 µg/kg) were administered to 4 week-old TRAMP mice intraperitoneal (i.p.) 3×/week on a MWF schedule for 14 weeks. Calcitriol and QW slowed progression of prostate cancer as indicated by reduced urogenital tract (p = 0.0022, calcitriol; p = 0.0009, QW) and prostate weights (p = 0.0178, calcitriol; p = 0.0086, QW). However, only calcitriol increased expression of the pro-differentiation marker, cadherin 1 (p = 0.0086), and reduced tumor proliferation (p = 0.0467). By contrast, neither vitamin D analog had any effect on castration resistant prostate cancer in mice treated pre- or post-castration. Interestingly, although vitamin D showed inhibitory activity against primary tumors in hormone-intact mice, distant organ metastases seemed to be enhanced following treatment (p = 0.0823). Therefore, TRAMP mice were treated long-term with calcitriol to further examine effects on metastasis. Calcitriol significantly increased the number of distant organ metastases when mice were treated from 4 weeks-of-age until development of palpable tumors (20–25 weeks-of-age)(p = 0.0003). Overall, data suggest that early intervention with vitamin D in TRAMP slowed androgen-stimulated tumor progression, but prolonged treatment resulted in development of a resistant and more aggressive disease associated with increased distant organ metastasis. PMID:24586868

  4. Decision analytic cost-effectiveness model to compare prostate cryotherapy to androgen deprivation therapy for treatment of radiation recurrent prostate cancer

    PubMed Central

    Boyd, Kathleen A; Jones, Rob J; Paul, Jim; Birrell, Fiona; Briggs, Andrew H; Leung, Hing Y

    2015-01-01

    Objective To determine the cost-effectiveness of salvage cryotherapy (SC) in men with radiation recurrent prostate cancer (RRPC). Design Cost-utility analysis using decision analytic modelling by a Markov model. Setting and methods Compared SC and androgen deprivation therapy (ADT) in a cohort of patients with RRPC (biopsy proven local recurrence, no evidence of metastatic disease). A literature review captured published data to inform the decision model, and resource use data were from the Scottish Prostate Cryotherapy Service. The model was run in monthly cycles for RRPC men, mean age of 70 years. The model was run over the patient lifetime, to assess changes in patient health states and the associated quality of life, survival and cost impacts. Results are reported in terms of the discounted incremental costs and discounted incremental quality-adjusted life years (QALYs) gained between the 2 alternative interventions. Probabilistic sensitivity analysis used a 10 000 iteration Monte Carlo simulation. Results SC has a high upfront treatment cost, but delays the ongoing monthly cost of ADT. SC is the dominant strategy over the patient lifetime; it is more effective with an incremental 0.56 QALY gain (95% CI 0.28 to 0.87), and less costly with a reduced lifetime cost of £29 719 (€37 619) (95% CI −51 985 to −9243). For a ceiling ratio of £30 000, SC has a 100% probability to be cost-effective. The cost neutral point was at 3.5 years, when the upfront cost of SC (plus any subsequent cumulative cost of side effects and ADT) equates the cumulative cost in the ADT arm. Limitations of our model may arise from its insensitivity to parameter or structural uncertainty. Conclusions The platform for SC versus ADT cost-effective analysis can be employed to evaluate other treatment modalities or strategies in RRPC. SC is the dominant strategy, costing less over a patient's lifetime with improvements in QALYs. Trial registration number This economic analysis

  5. Risks of Prostate Cancer Screening

    MedlinePlus

    ... prostate. The prostate is a gland in the male reproductive system located just below the bladder (the organ that ... up part of semen . Enlarge Anatomy of the male reproductive and urinary systems, showing the prostate, testicles, bladder, and other organs. ...

  6. Treatment Option Overview (Prostate Cancer)

    MedlinePlus

    ... prostate. The prostate is a gland in the male reproductive system . It lies just below the bladder (the organ ... part of the semen . Enlarge Anatomy of the male reproductive and urinary systems, showing the prostate, testicles, bladder, and other organs. ...

  7. General Information about Prostate Cancer

    MedlinePlus

    ... prostate. The prostate is a gland in the male reproductive system . It lies just below the bladder (the organ ... part of the semen . Enlarge Anatomy of the male reproductive and urinary systems, showing the prostate, testicles, bladder, and other organs. ...

  8. Targeted prodrug approaches for hormone refractory prostate cancer.

    PubMed

    Aloysius, Herve; Hu, Longqin

    2015-05-01

    Due to the propensity of relapse and resistance with prolonged androgen deprivation therapy (ADT), there is a growing interest in developing non-hormonal therapeutic approaches as alternative treatment modalities for hormone refractory prostate cancer (HRPC). Although the standard treatment for HRPC consists of a combination of ADT with taxanes and anthracyclines, the clinical use of chemotherapeutics is limited by systemic toxicity stemming from nondiscriminatory drug exposure to normal tissues. In order to improve the tumor selectivity of chemotherapeutics, various targeted prodrug approaches have been explored. Antibody-directed enzyme prodrug therapy (ADEPT) and gene-directed enzyme prodrug therapy (GDEPT) strategies leverage tumor-specific antigens and transcription factors for the specific delivery of cytotoxic anticancer agents using various prodrug-activating enzymes. In prostate cancer, overexpression of tumor-specific proteases such as prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) is being exploited for selective activation of anticancer prodrugs designed to be activated through proteolysis by these prostate cancer-specific enzymes. PSMA- and PSA-activated prodrugs typically comprise an engineered high-specificity protease peptide substrate coupled to a potent cytotoxic agent via a linker for rapid release of cytotoxic species in the vicinity of prostate cancer cells following proteolytic cleavage. Over the past two decades, various such prodrugs have been developed and they were effective at inhibiting prostate tumor growth in rodent models; several of these prodrug approaches have been advanced to clinical trials and may be developed into effective therapies for HRPC.

  9. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

    DTIC Science & Technology

    2014-09-01

    saturation bands (six for fat and two for water) were used to minimize lipid/water contamination to the VOI. The 2D MRSI sequence details are: TR/TE... fat as measured by in-vivo imaging using proton magnetic resonance spectroscopy imaging in the prediction of prostate disease aggressiveness...histology, in-vivo intraprostatic fat as measured by 1H MRSI, metabolic signatures of lipid oxidation and metabolism, and prostate cancer

  10. Incidence of prostate cancer in Lithuania after introduction of the Early Prostate Cancer Detection Programme.

    PubMed

    Smailyte, G; Aleknaviciene, B

    2012-12-01

    In Lithuania, prostate-specific antigen (PSA) testing is offered to healthy asymptomatic men as a screening test in the population-based Early Prostate Cancer Detection Programme (EPCDP). The aim of this study was to analyse the incidence of prostate cancer before and after introduction of the EPCDP in Lithuania. Prostate cancer incidence and mortality data from the Lithuanian Cancer Registry were analysed for the period 1990-2008. Age-specific incidence and mortality data were adjusted to the European Standard Population. There have been extraordinary changes in the incidence of prostate cancer in Lithuania following introduction of the EPCDP, and there is strong evidence that these changes are the result of increased detection rates, especially in men of screening age. Further observation of changes in prostate cancer incidence and mortality in Lithuania may help to determine the extent to which PSA testing at the population level influences incidence and mortality in the general population.

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

    PubMed

    Lokant, M T; Naz, R K

    2015-04-01

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

  12. Humanin: A Novel Therapeutic Target in Prostate Cancer

    DTIC Science & Technology

    2007-01-01

    benign prostatic hyperplasia (BPH; n=107), prostatic intraepithelial neoplasia (PIN; n=41) and invasive prostate cancer (Cancer; n=574). Both cytoplasmic...expression was significantly higher in cancer (ProsCa) compared to normal (NL; p=0028), and benign prostatic hyperplasia (BPH; p=0.0017). Humanin expression

  13. Impact of Prostate Inflammation on Lesion Development in the POET3+Pten+/− Mouse Model of Prostate Carcinogenesis

    PubMed Central

    Burcham, Grant N.; Cresswell, Gregory M.; Snyder, Paul W.; Chen, Long; Liu, Xiaoqi; Crist, Scott A.; Henry, Michael D.; Ratliff, Timothy L.

    2015-01-01

    Evidence linking prostatitis and prostate cancer development is contradictory. To study this link, the POET3 mouse, an inducible model of prostatitis, was crossed with a Pten-loss model of prostate cancer (Pten+/−) containing the ROSA26 luciferase allele to monitor prostate size. Prostatitis was induced, and prostate bioluminescence was tracked over 12 months, with lesion development, inflammation, and cytokine expression analyzed at 4, 8, and 12 months and compared with mice without induction of prostatitis. Acute prostatitis led to more proliferative epithelium and enhanced bioluminescence. However, 4 months after initiation of prostatitis, mice with induced inflammation had lower grade pre-neoplastic lesions. A trend existed toward greater development of carcinoma 12 months after induction of inflammation, including one of two mice with carcinoma developing perineural invasion. Two of 18 mice at the later time points developed lesions with similarities to proliferative inflammatory atrophy, including one mouse with associated carcinoma. Pten+/− mice developed spontaneous inflammation, and prostatitis was similar among groups of mice at 8 and 12 months. Analyzed as one cohort, lesion number and grade were positively correlated with prostatitis. Specifically, amounts of CD11b+Gr1+ cells were correlated with lesion development. These results support the hypothesis that myeloid-based inflammation is associated with lesion development in the murine prostate, and previous bouts of CD8-driven prostatitis may promote invasion in the Pten+/− model of cancer. PMID:25455686

  14. Targeting the Neural Microenvironment in Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    SUPPLEMENTARY NOTES 14. ABSTRACT Prostate cancer (PCa) remains the most common malignancy and the second leading cause of cancer-related death for men in the...cancer (PCa) remains the most common malignancy and the second leading cause of cancer-related death for men in the United States. The tumor

  15. Primary and salvage cryotherapy for prostate cancer.

    PubMed

    Finley, David S; Pouliot, Frederic; Miller, David C; Belldegrun, Arie S

    2010-02-01

    Cryotherapy is a technique to ablate tissue by local induction of extremely cold temperatures. Recently, the American Urological Association Best Practice Statement recognized cryoablation of the prostate as an established treatment option for men with newly diagnosed or radiorecurrent organ-confined prostate cancer. Emerging data suggest that, in select cases, cryoablation may have a role in focal ablation of prostate. The current state of the art of cryoablation in these applications is reviewed.

  16. Prediction of Erectile Function Following Treatment for Prostate Cancer

    PubMed Central

    Alemozaffar, Mehrdad; Regan, Meredith M.; Cooperberg, Matthew R.; Wei, John T.; Michalski, Jeff M.; Sandler, Howard M.; Hembroff, Larry; Sadetsky, Natalia; Saigal, Christopher S.; Litwin, Mark S.; Klein, Eric; Kibel, Adam S.; Hamstra, Daniel A.; Pisters, Louis L.; Kuban, Deborah A.; Kaplan, Irving D.; Wood, David P.; Ciezki, Jay; Dunn, Rodney L.; Carroll, Peter R.; Sanda, Martin G.

    2013-01-01

    Context Sexual function is the health-related quality of life (HRQOL) domain most commonly impaired after prostate cancer treatment; however, validated tools to enable personalized prediction of erectile dysfunction after prostate cancer treatment are lacking. Objective To predict long-term erectile function following prostate cancer treatment based on individual patient and treatment characteristics. Design Pretreatment patient characteristics, sexual HRQOL, and treatment details measured in a longitudinal academic multicenter cohort (Prostate Cancer Outcomes and Satisfaction With Treatment Quality Assessment; enrolled from 2003 through 2006), were used to develop models predicting erectile function 2 years after treatment. A community-based cohort (community-based Cancer of the Prostate Strategic Urologic Research Endeavor [CaPSURE]; enrolled 1995 through 2007) externally validated model performance. Patients in US academic and community-based practices whose HRQOL was measured pretreatment (N = 1201) underwent follow-up after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer. Sexual outcomes among men completing 2 years’ follow-up (n = 1027) were used to develop models predicting erectile function that were externally validated among 1913 patients in a community-based cohort. Main Outcome Measures Patient-reported functional erections suitable for intercourse 2 years following prostate cancer treatment. Results Two years after prostate cancer treatment, 368 (37% [95% CI, 34%–40%]) of all patients and 335 (48% [95% CI, 45%–52%]) of those with functional erections prior to treatment reported functional erections; 531 (53% [95% CI, 50%–56%]) of patients without penile prostheses reported use of medications or other devices for erectile dysfunction. Pretreatment sexual HRQOL score, age, serum prostate-specific antigen level, race/ethnicity, body mass index, and intended treatment details were associated with functional erections 2

  17. Evolving Recommendations on Prostate Cancer Screening.

    PubMed

    Brawley, Otis W; Thompson, Ian M; Grönberg, Henrik

    2016-01-01

    Results of a number of studies demonstrate that the serum prostate-specific antigen (PSA) in and of itself is an inadequate screening test. Today, one of the most pressing questions in prostate cancer medicine is how can screening be honed to identify those who have life-threatening disease and need aggressive treatment. A number of efforts are underway. One such effort is the assessment of men in the landmark Prostate Cancer Prevention Trial that has led to a prostate cancer risk calculator (PCPTRC), which is available online. PCPTRC version 2.0 predicts the probability of the diagnosis of no cancer, low-grade cancer, or high-grade cancer when variables such as PSA, age, race, family history, and physical findings are input. Modern biomarker development promises to provide tests with fewer false positives and improved ability to find high-grade cancers. Stockholm III (STHLM3) is a prospective, population-based, paired, screen-positive, prostate cancer diagnostic study assessing a combination of plasma protein biomarkers along with age, family history, previous biopsy, and prostate examination for prediction of prostate cancer. Multiparametric MRI incorporates anatomic and functional imaging to better characterize and predict future behavior of tumors within the prostate. After diagnosis of cancer, several genomic tests promise to better distinguish the cancers that need treatment versus those that need observation. Although the new technologies are promising, there is an urgent need for evaluation of these new tests in high-quality, large population-based studies. Until these technologies are proven, most professional organizations have evolved to a recommendation of informed or shared decision making in which there is a discussion between the doctor and patient.

  18. 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

    AWARD NUMBER: W81XWH-13-1-0162 TITLE: Using a Novel Transgenic Mouse Model to Study c-Myc...CONTRACT NUMBER Using a Novel Transgenic Mouse Model to Study c-Myc Oncogenic Pathway in Castration Resistance and Chemoresistance of Prostate Cancer...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT We previously generated a PB-Cre4/CAG-SMIL transgenic model allowing Cre

  19. Hormones and prostate cancer: what's next?

    PubMed

    Hsing, A W

    2001-01-01

    In summary, the hormonal hypothesis remains one of the most important hypotheses in prostate cancer etiology. Although epidemiologic data regarding the role of hormones are still inconclusive, there are many intriguing leads. Armed with more complete methodological data, state-of-the-art hormone assays, sound epidemiologic design, and a more thorough analytical approach, a new generation of studies should yield critical data and insights to help clarify further the role of hormones in prostate cancer. These new studies may determine ultimately whether racial/ethnic differences in hormonal levels and in genetic susceptibility to hormone-metabolizing genes can help explain the very large racial/ethnic differences in prostate cancer risk.

  20. Novel diagnostic biomarkers for prostate cancer

    PubMed Central

    Madu, Chikezie O.; Lu, Yi

    2010-01-01

    Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the disease is diagnosed early. Thus, a successful therapy for this disease depends heavily on the clinical indicators (biomarkers) for early detection of the presence and progression of the disease, as well as the prediction after the clinical intervention. However, the current clinical biomarkers for prostate cancer are not ideal as there remains a lack of reliable biomarkers that can specifically distinguish between those patients who should be treated adequately to stop the aggressive form of the disease and those who should avoid overtreatment of the indolent form. A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker reveals further information to presently existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for individual patients. The form of the prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues. Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of prostate cancer. The

  1. Antitumor Effects of Saffron-Derived Carotenoids in Prostate Cancer Cell Models

    PubMed Central

    Festuccia, Claudio; Mancini, Andrea; Gravina, Giovanni Luca; Scarsella, Luca; Llorens, Silvia; Alonso, Gonzalo L.; Tatone, Carla; Di Cesare, Ernesto; Jannini, Emmanuele A.; Lenzi, Andrea; D'Alessandro, Anna M.; Carmona, Manuel

    2014-01-01

    Crocus sativus L. extracts (saffron) are rich in carotenoids. Preclinical studies have shown that dietary intake of carotenoids has antitumor effects suggesting their potential preventive and/or therapeutic roles. We have recently reported that saffron (SE) and crocin (CR) exhibit anticancer activity by promoting cell cycle arrest in prostate cancer (PCa) cells. It has also been demonstrated that crocetin esters are produced after SE gastrointestinal digestion by CR hydrolysis. The aim of the present report was to investigate if SE, crocetin (CCT), and CR affected in vivo tumor growth of two aggressive PCa cell lines (PC3 and 22rv1) which were xenografted in male nude mice treated by oral gavage with SE, CR, and CCT. We demonstrated that the antitumor effects of CCT were higher when compared to CR and SE and treatments reverted the epithelial-mesenchymal transdifferentiation (EMT) as attested by the significant reduction of N-cadherin and beta-catenin expression and the increased expression of E-cadherin. Additionally, SE, CR, and CCT inhibited PCa cell invasion and migration through the downmodulation of metalloproteinase and urokinase expression/activity suggesting that these agents may affect metastatic processes. Our findings suggest that CR and CCT may be dietary phytochemicals with potential antitumor effects in biologically aggressive PCa cells. PMID:24900952

  2. FOXA1 regulates androgen receptor variant activity in models of castrate-resistant prostate cancer

    PubMed Central

    Nakjang, Sirintra; Chaytor, Lewis; Grey, James; Robson, Craig N.; Gaughan, Luke

    2015-01-01

    Retention of androgen receptor (AR) signalling in castrate-resistant prostate cancer (CRPC) highlights the requirement for the development of more effective AR targeting therapies. A key mechanism of resistance to anti-androgens is through expression of constitutively active AR variants (AR-Vs) that are refractory to next-generation therapies, including Enzalutamide and Abiraterone. By maintaining an androgenic gene signature, AR-Vs drive tumour survival and progression in castrate conditions. Critically, however, our understanding of the mechanics of AR-V-driven transcription is limited, particularly with respect to dependency on pioneer factor function. Here we show that depletion of FOXA1 in the CWR22Rv1 CRPC cell line abrogates the oncogenic potential of AR-Vs. Gene expression profiling reveals that approximately 41% of the AR-V transcriptome requires FOXA1 and that depletion of FOXA1 attenuates AR-V binding at a sub-set of analysed co-regulated genes. Interestingly, AR-V levels are elevated in cells depleted of FOXA1 as a consequence of attenuated negative feedback on the AR gene, but is insufficient to maintain cell growth as evidenced by marked anti-proliferative effects in FOXA1 knockdown cells. In all, our data suggests that AR-Vs are dependent on FOXA1 for sustaining a pro-proliferative gene signature and agents targeting FOXA1 may represent novel therapeutic options for CRPC patients. PMID:26336819

  3. FOXA1 regulates androgen receptor variant activity in models of castrate-resistant prostate cancer.

    PubMed

    Jones, Dominic; Wade, Mark; Nakjang, Sirintra; Chaytor, Lewis; Grey, James; Robson, Craig N; Gaughan, Luke

    2015-10-06

    Retention of androgen receptor (AR) signalling in castrate-resistant prostate cancer (CRPC) highlights the requirement for the development of more effective AR targeting therapies. A key mechanism of resistance to anti-androgens is through expression of constitutively active AR variants (AR-Vs) that are refractory to next-generation therapies, including Enzalutamide and Abiraterone. By maintaining an androgenic gene signature, AR-Vs drive tumour survival and progression in castrate conditions. Critically, however, our understanding of the mechanics of AR-V-driven transcription is limited, particularly with respect to dependency on pioneer factor function. Here we show that depletion of FOXA1 in the CWR22Rv1 CRPC cell line abrogates the oncogenic potential of AR-Vs. Gene expression profiling reveals that approximately 41% of the AR-V transcriptome requires FOXA1 and that depletion of FOXA1 attenuates AR-V binding at a sub-set of analysed co-regulated genes. Interestingly, AR-V levels are elevated in cells depleted of FOXA1 as a consequence of attenuated negative feedback on the AR gene, but is insufficient to maintain cell growth as evidenced by marked anti-proliferative effects in FOXA1 knockdown cells. In all, our data suggests that AR-Vs are dependent on FOXA1 for sustaining a pro-proliferative gene signature and agents targeting FOXA1 may represent novel therapeutic options for CRPC patients.

  4. Nanotherapies for treating prostate cancer

    NASA Astrophysics Data System (ADS)

    Danquah, Michael

    Current prostate cancer treatment remains ineffective primarily due to ineffectual therapeutic strategies and numerous tumor-associated physiological barriers which hinder efficacy of anticancer agents. Therefore, the focus of this study was to investigate a new combination therapy approach for treating prostate cancer and develop polymeric nanocarriers to facilitate anticancer drug and nucleic acid delivery. It was hypothesized that simultaneously targeting androgen-androgen receptor (AR) and X-linked inhibitor of apoptosis protein (XIAP) signaling pathways would be effective in treating prostate cancer. The effect of bicalutamide (antiandrogen) and embelin (XIAP inhibitor) on the growth of prostate cancer cells in vitro and in vivo was first examined. Embelin induced caspase 3 and 9 activation in LNCaP and C4-2 cells by decreasing XIAP expression and was more potent than bicalutamide in killing prostate tumor cells irrespective of their androgen status. Using a combination of MTT assay and isobologram analyses, combination of bicalutamide and embelin was observed to be cell line and schedule dependent. Since bicalutamide and embelin are extremely hydrophobic, polymeric micelles were fabricated using polyethylene glycol-b-polylactic acid (PEG-b-PLA) copolymer to improve drug solubility. Micellar formulations were found to result in at least 60-fold increase in the aqueous solubility of bicalutamide and embelin. Tumor growth was also effectively regressed upon treatment with bicalutamide, but the extent of tumor regression was significantly higher when bicalutamide was formulated in micelles. To further improve bicalutamide aqueous solubility, a series of novel biodegradable copolymers for the systematic micellar delivery of bicalutamide was designed and synthesized. Flory-Huggins interaction parameter (χFH) was used to assess compatibility between bicalutamide and poly (L-lactide) or poly (carbonate-co-lactide) polymer pairs. Polyethylene glycol-b-poly (carbonate

  5. Molecular genetics of prostate cancer: new prospects for old challenges

    PubMed Central

    Shen, Michael M.; Abate-Shen, Cory

    2010-01-01

    Despite much recent progress, prostate cancer continues to represent a major cause of cancer-related mortality and morbidity in men. Since early studies on the role of the androgen receptor that led to the advent of androgen deprivation therapy in the 1940s, there has long been intensive interest in the basic mechanisms underlying prostate cancer initiation and progression, as well as the potential to target these processes for therapeutic intervention. Here, we present an overview of major themes in prostate cancer research, focusing on current knowledge of principal events in cancer initiation and progression. We discuss recent advances, including new insights into the mechanisms of castration resistance, identification of stem cells and tumor-initiating cells, and development of mouse models for preclinical evaluation of novel therapuetics. Overall, we highlight the tremendous research progress made in recent years, and underscore the challenges that lie ahead. PMID:20844012

  6. Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer

    ClinicalTrials.gov

    2016-11-23

    Hormone-Resistant Prostate Cancer; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

  7. The integrated proactive surveillance system for prostate cancer.

    PubMed

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

    2012-01-01

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

  8. Boosting antitumor responses of T lymphocytes infiltrating human prostate cancers.

    PubMed

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

    2005-04-18

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

  9. Functional imaging for prostate cancer: therapeutic implications.

    PubMed

    Mari Aparici, Carina; Seo, Youngho

    2012-09-01

    Functional radionuclide imaging modalities, now commonly combined with anatomical imaging modalities computed tomography (CT) or magnetic resonance imaging (single photon emission computed tomography [SPECT]/CT, positron emission tomography [PET]/CT, and PET/magnetic resonance imaging), 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 regard 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, although 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.

  10. Farming, reported pesticide use, and prostate cancer.

    PubMed

    Ragin, Camille; Davis-Reyes, Brionna; Tadesse, Helina; Daniels, Dennis; Bunker, Clareann H; Jackson, Maria; Ferguson, Trevor S; Patrick, Alan L; Tulloch-Reid, Marshall K; Taioli, Emanuela

    2013-03-01

    Prostate cancer is the leading cancer type diagnosed in American men and is the second leading cancer diagnosed in men worldwide. Although studies have been conducted to investigate the association between prostate cancer and exposure to pesticides and/or farming, the results have been inconsistent. We performed a meta-analysis to summarize the association of farming and prostate cancer. The PubMed database was searched to identify all published case-control studies that evaluated farming as an occupational exposure by questionnaire or interview and prostate cancer. Ten published and two unpublished studies were included in this analysis, yielding 3,978 cases and 7,393 controls. Prostate cancer cases were almost four times more likely to be farmers compared with controls with benign prostate hyperplasia (BPH; meta odds ratio [OR], crude = 3.83, 95% confidence interval [CI] = 1.96-7.48, Q-test p value = .352; two studies); similar results were obtained when non-BPH controls were considered, but with moderate heterogeneity between studies (meta OR crude = 1.38, 95% CI = 1.16-1.64, Q-test p value = .216, I (2) = 31% [95% CI = 0-73]; five studies). Reported pesticide exposure was inversely associated with prostate cancer (meta OR crude = 0.68, 95% CI = 0.49-0.96, Q-test p value = .331; four studies), whereas no association with exposure to fertilizers was observed. Our findings confirm that farming is a risk factor for prostate cancer, but this increased risk may not be due to exposure to pesticides.

  11. Molecular pathways and targets in prostate cancer

    PubMed Central

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

    2014-01-01

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

  12. Survivin Is a Potential Mediator of Prostate Cancer Metastasis

    SciTech Connect

    Zhang Min; Coen, John J.; Khor, Li-Yan; Pollack, Alan; Zhang Yifen; Zietman, Anthony L.; Shipley, William U.

    2010-11-15

    Purpose: We examined whether Survivin expression is associated with an increased risk of metastasis in prostate cancer. Methods and Materials: A total of 205 patients with T1 (23%) and T2 (77%) prostate cancer were treated with conventional external beam radiation therapy from 1991 to 1993 at the Massachusetts General Hospital. Of the patients, 62 had adequate and suitable-stained tumor material for Survivin analysis. Median follow-up was 102 months (range, 5-127 months). Distant failure was determined on the basis of clinical criteria. In preclinical studies, replication-deficient adenovirus encoding phosphorylation-defective Survivin Thr34{yields}Ala dominant-negative mutant pAd-S(T34A) or short hairpin RNA (shRNA) was used to inhibit Survivin in prostate cancer models, and the cell motility, morphology, and metastasis were investigated. Results: Our correlative data on men with early-stage (T1/T2) prostate cancers treated at Massachusetts General Hospital by definitive radiotherapy indicated that overexpression of Survivin (positive staining in {>=}10% cells) was associated with a significantly increased risk for the subsequent development of distant metastasis (p = 0.016) in the univariate analysis. In the multivariate analysis, overexpression of Survivin remained an independent predictor of distant metastasis (p = 0.008). The inhibition of Survivin dramatically inhibited invasiveness of prostate cancer cells in the in vitro invasion assay and spontaneous metastasis in the Dunning prostate cancer in vivo model. Furthermore, attenuation of Survivin resulted in changes in the microtubule cytoskeleton, loss of cellular polarity, and loss of motility. Conclusions: This study suggests that Survivin may be a potentially important prognostic marker and promising therapeutic target in metastatic prostate cancer.

  13. Management of Complications of Prostate Cancer Treatment

    PubMed Central

    Michaelson, M. Dror; Cotter, Shane E.; Gargollo, Patricio C.; Zietman, Anthony L.; Dahl, Douglas M.; Smith, Matthew R.

    2010-01-01

    Prostate cancer is the most commonly diagnosed noncutaneous cancer in men in the United States. Treatment of men with prostate cancer commonly involves surgical, radiation, or hormone therapy. Most men with prostate cancer live for many years after diagnosis and may never suffer morbidity or mortality attributable to prostate cancer. The short-term and long-term adverse consequences of therapy are, therefore, of great importance. Adverse effects of radical prostatectomy include immediate postoperative complications and long-term urinary and sexual complications. External beam or interstitial radiation therapy in men with localized prostate cancer may lead to urinary, gastrointestinal, and sexual complications. Improvements in surgical and radiation techniques have reduced the incidence of many of these complications. Hormone treatment typically consists of androgen deprivation therapy, and consequences of such therapy may include vasomotor flushing, anemia, and bone density loss. Numerous clinical trials have studied the role of bone antiresorptive therapy for prevention of bone density loss and fractures. Other long-term consequences of androgen deprivation therapy may include adverse body composition changes and increased risk of insulin resistance, diabetes, and cardiovascular disease. Ongoing and planned clinical trials will continue to address strategies to prevent treatment-related side effects and improve quality of life for men with prostate cancer. PMID:18502900

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

    PubMed Central

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

    2016-01-01

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

  15. Prostate Cancer Stem Cells: Research Advances

    PubMed Central

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease. PMID:26593898

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

    ClinicalTrials.gov

    2016-05-06

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

  17. Exosomes as Novel microRNA-Delivery Vehicles to Modulate Prostate Cancer Progression

    DTIC Science & Technology

    2015-10-01

    specifically packaged in these 40-100 nm microvesicles and secreted from prostate cancer cells are important in the progression to aggressive disease...behavior of aggressive human prostate cancer cell lines in vitro as well as in vivo using mouse xenograft models. 15. SUBJECT TERMS microRNAs, exosomes...microvesicles and secreted from prostate cancer cells are important in the progression to aggressive disease. In this exploratory award, we are

  18. Molecular Engineering of Vector-Based Oncolytic and Imaging Approaches for Advanced Prostate Cancer

    DTIC Science & Technology

    2006-02-01

    Oncolytic and Imaging Approaches for Advanced Prostate Cancer PRINCIPAL INVESTIGATOR: Lily Wu, M.D., Ph.D. CONTRACTING ORGANIZATION...SUBTITLE Molecular Engineering of Vector-based Oncolytic and Imaging Approaches for 5a. CONTRACT NUMBER Advanced Prostate Cancer 5b. GRANT...reproductions will be in black and white. 14. ABSTRACT Hormone refractory and metastatic prostate cancer are not well understood. Better animal models

  19. The Potential Use of Glycine to Enhance Radiation Therapy for Prostate Cancer

    DTIC Science & Technology

    2012-09-01

    Radiation Therapy for Prostate Cancer PRINCIPAL INVESTIGATOR: Brian Kavanagh CONTRACTING ORGANIZATION: University of Colorado...Enhance Radiation Therapy for Prostate Cancer 5b. GRANT NUMBER W81XWH-11-1-0363 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Betty Diamond...radiation-induced Hif-1α expression and created a favorable growth delay in the xenograft model. 15. SUBJECT TERMS Prostate cancer , hif-1

  20. Decision Analysis of the Benefits and Costs of Screening for Prostate Cancer

    DTIC Science & Technology

    2013-08-01

    Proton Beam Therapy for Treatment of Clinically Localized, Low-Risk Prostate Cancer 2009; http://www.icer-review.org/index.php/bt- pbt.html. Accessed...exciting. As part of a project that is evolving out of this model – assessing the cost-effectiveness of adjuvant therapies for prostate cancer – I will...Costs of Screening for Prostate Cancer PRINCIPAL INVESTIGATOR: Julia H. Hayes, M.D

  1. Mechanisms of Chinese Red Yeast Rice Inhibition of Prostate Cancer Growth

    DTIC Science & Technology

    2009-04-01

    Early prostate cancer is androgen -dependent, but in later stages of the disease androgen -independent tumors arise with an eventual fatal outcome...Medicinal Food 11:657-666, 2008 (Title: Chinese red yeast rice vs lovastatin effects on prostate cancer cells with and without androgen receptor...overexpression) (This paper is attached in appendix). Based on the in vitro study, androgen -dependent and –independent prostate cancer xenograft model

  2. Radium-223 for Advanced Prostate Cancer

    Cancer.gov

    A summary of results from a phase III trial that compared radium-223 dichloride plus the best standard of care versus a placebo plus the best standard of care in men with metastatic, castration-resistant prostate cancer.

  3. Clinical controversies: proton therapy for prostate cancer.

    PubMed

    Mouw, Kent W; Trofimov, Alexei; Zietman, Anthony L; Efstathiou, Jason A

    2013-04-01

    Proton therapy has been used in the treatment of prostate cancer for several decades, and interest surrounding its use continues to grow. Proton-based treatment techniques have evolved significantly over this period, and several centers now routinely use technologies such as pencil-beam scanning. However, whether the theoretical dosimetric advantages of the proton beam translate into clinically meaningful improvements for prostate cancer patients is unknown, and outcomes from single-arm experiences using whole courses of proton beam therapy in the treatment of early-stage prostate cancer have shown mixed results when compared with contemporary intensity-modulated radiotherapy. A randomized trial comparing proton beam therapy with intensity-modulated radiotherapy in early-stage disease has been launched and will be important in defining the role for proton therapy in this setting. We review the available evidence and present the current state of proton beam therapy for prostate cancer.

  4. Abiraterone Improves Survival in Metastatic Prostate Cancer

    Cancer.gov

    A multinational phase III trial found that the drug abiraterone acetate prolonged the median survival of patients with metastatic castration-resistant prostate cancer by 4 months compared with patients who received a placebo.

  5. Do We Know What Causes Prostate Cancer?

    MedlinePlus

    ... account for a small number of prostate cancers. DNA mismatch repair genes (such as MSH2 and MLH1 ): These genes normally help fix mistakes (mismatches) in DNA that are made when a cell is preparing ...

  6. Effects of Presurgical Treatment for Prostate Cancer

    Cancer.gov

    In this study, men diagnosed with androgen-sensitive prostate cancer with intermediate- or high-risk features will be examined with mpMRI, undergo targeted biopsies, and be treated with neoadjuvant androgen deprivation therapy.

  7. Validation of Biomarkers for Prostate Cancer Prognosis

    DTIC Science & Technology

    2013-10-01

    incontinence and urinary urgency as well as sexual dysfunction. Furthermore, evidence from many sources suggests that most prostate cancers are...mainly surgery and radiation therapy, result in well documented significant morbidities, including significant lower urinary tract symptoms such as

  8. Testosterone therapy and prostate cancer

    PubMed Central

    Pastuszak, Alexander W.; Rodriguez, Katherine M.; Nguyen, Taylor M.

    2016-01-01

    The use of exogenous testosterone to treat hypogonadism in the men with a history of prostate cancer (CaP) remains controversial due to fears of cancer recurrence or progression. Due to the detrimental impact of hypogonadism on patient quality of life, recent work has examined the safety of testosterone therapy (TTh) in men with a history of CaP. In this review, we evaluate the literature with regards to the safety of TTh in men with a history of CaP. TTh results in improvements in quality of life with little evidence of biochemical recurrence or progression in men with a history of CaP, or de novo cancer in unaffected men. An insufficient amount of evidence is currently available to truly demonstrate the safe use of TTh in men with low risk CaP. In men with high-risk cancer, more limited data suggest that TTh may be safe, but these findings remain inconclusive. Despite the historic avoidance of TTh in men with a history of CaP, the existing body of evidence largely supports the safe and effective use of testosterone in these men, although additional study is needed before unequivocal safety can be demonstrated. PMID:28078223

  9. Oncolytic adenovirus-mediated therapy for prostate cancer

    PubMed Central

    Sweeney, Katrina; Halldén, Gunnel

    2016-01-01

    Prostate cancer is a leading cause of cancer-related death and morbidity in men in the Western world. Tumor progression is dependent on functioning androgen receptor signaling, and initial administration of antiandrogens and hormone therapy (androgen-deprivation therapy) prevent growth and spread. Tumors frequently develop escape mechanisms to androgen-deprivation therapy and progress to castration-resistant late-stage metastatic disease that, in turn, inevitably leads to resistance to all current therapeutics, including chemotherapy. In spite of the recent development of more effective inhibitors of androgen–androgen receptor signaling such as enzalutamide and abiraterone, patient survival benefits are still limited. Oncolytic adenoviruses have proven efficacy in prostate cancer cells and cause regression of tumors in preclinical models of numerous drug-resistant cancers. Data from clinical trials demonstrate that adenoviral mutants have limited toxicity to normal tissues and are safe when administered to patients with various solid cancers, including prostate cancer. While efficacy in response to adenovirus administration alone is marginal, findings from early-phase trials targeting local-ized and metastatic prostate cancer suggest improved efficacy in combination with cytotoxic drugs and radiation therapy. Here, we review recent progress in the development of multimodal oncolytic adenoviruses as biological therapeutics to improve on tumor elimination in prostate cancer patients. These optimized mutants target cancer cells by several mechanisms including viral lysis and by expression of cytotoxic transgenes and immune-stimulatory factors that activate the host immune system to destroy both infected and noninfected prostate cancer cells. Additional modifications of the viral capsid proteins may support future systemic delivery of oncolytic adenoviruses. PMID:27579296

  10. Serum selenium levels and prostate cancer risk

    PubMed Central

    Cui, Zhigang; Liu, Dezhong; Liu, Chun; Liu, Gang

    2017-01-01

    Abstract Some observational studies have shown that elevated serum selenium levels are associated with reduced prostate cancer risk; however, not all published studies support these results. A literature search of PubMed, Embase, Medline, and the Cochrane Library up until September 2016 identified 17 studies suitable for further investigation. A meta-analysis was conducted on these studies to investigate the association between serum selenium levels and subsequent prostate cancer risk. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the overall OR of prostate cancer for the highest versus the lowest levels of serum selenium. We found a pooled OR (95% CI) of 0.76 (0.64, 0.91; P < 0.05). In subgroup analysis, an inverse association between serum selenium levels and prostate cancer risk was found in each of case–control studies, current and former smokers, high-grade cancer cases, advanced cancer cases, and different populations. Such correlations were not found for subgroups containing each of cohort studies, nonsmokers, low-grade cancer cases, and early stage cancer cases. In conclusion, our study suggests an inverse relationship between serum selenium levels and prostate cancer risk. However, further cohort studies and randomized control trials based on non-Western populations are required. PMID:28151881

  11. Circadian Genes and Risk for Prostate Cancer

    DTIC Science & Technology

    2012-11-01

    randomized placebo-controlled clinical trial to determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer...and that this risk differed between men who took finasteride versus those who took the placebo. The strongest association was seen for a cluster of 9...SNPs in NPAS2, which was associated with total prostate cancer risk in the finasteride group but not in the placebo group. The most significant NPAS2

  12. Imaging Prostate Cancer (Pca) Phenotype and Evolution

    DTIC Science & Technology

    2014-10-01

    prostate cancer cells. To further investigate the effects of DFP on prostate cancer cells we carried out extracellular flux analysis experiments. Our...Extracellular flux analysis experiments with the Seahorse system showed a marked decrease in OCR after inhibition of ATP synthase by oligomycin...the means. Figure 5 – Extracellular flux analysis in TRAMP C2 cells incubated with different concentrations of DFP. Left: OCR measurements. Right

  13. Characterization of SPINK1 in Prostate Cancer

    DTIC Science & Technology

    2009-07-01

    rearrangement by FISH. A TMPRSS2:ERG rearrangement through intrachromosomal deletion is indicated by loss of one 50 ( green ) ERG signal. (B) Contingency tables...pancreatic juice, its normal function is thought to be the inhibition of serine proteases such as trypsin ( Greene et al., 1976; Haverback et al., 1960; Kazal...lesions to function in prostate cancer, we assayed prostate cancer cell lines by quan- titative PCR for SPINK1 (yellow), ERG (blue), and ETV1 ( green

  14. Targeting TMPRSS2-ERG in Prostate Cancer

    DTIC Science & Technology

    2015-09-01

    ABSTRACT About half of all prostate cancers are known to harbor a genetic mutation that fuses a gene known as ERG to the regulatory region of the gene...activity. We applied this technique to screen genetic and chemical libraries to study ERG mediated tumorigenesis and identify novel therapeutic...agents targeting ERG activity. 15. SUBJECT TERMS Prostate cancer, ERG, gene expression, high throughput screening, small molecule microarray, genetic

  15. Enhancing Therapeutic Cellular Prostate Cancer Vaccines

    DTIC Science & Technology

    2013-06-01

    10-1-0225 TITLE: “Enhancing Therapeutic Cellular Prostate Cancer Vaccines ” PRINCIPAL INVESTIGATOR: Christian R. Gomez, Ph.D...SUBTITLE “Enhancing Therapeutic Cellular Prostate Cancer Vaccines ” 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-10-1-0225 5c. PROGRAM ELEMENT...cell CaP vaccines by taking into consideration tumor-associated hypoxia as a relevant determinant of tumor antigenicity. Major Findings: Gene

  16. Metallated DNA Aptamers For Prostate Cancer Treatment

    DTIC Science & Technology

    2012-03-01

    including a polydA tail in one aptamer complex and a polydT tail in a second aptamer complex, with dimerization occurring by Watson - Crick base pair...by ANSI Std. Z39.18 W81XWH-10-1-0132 Metallated DNA Aptamers for Prostate Cancer Treatment Dr. William Gmeiner Wake Forest University Winston...efficacious for prostate cancer treatment. Significant progress has been made on refining novel Zn2+-binding DNA motifs that utilize FdU

  17. Proteomics in prostate cancer research.

    PubMed

    Hellström, Magnus; Lexander, Helena; Franzén, Bo; Egevad, Lars

    2007-02-01

    The incidence of early prostate cancer (PCa) among middle-aged men has increased rapidly. For many of these men, curatively intended treatment does more harm than good. Established prognostic factors are tumor stage and grade. As a result of earlier detection a majority of patients now have nonpalpable tumors (T1c) of intermediate grade (Gleason score 6). Prostate specific antigen in serum in such cases is generally at a low level and not a reliable predictor of prognosis. Altogether there is an urgent need for adjunctive prognostic indicators. In the search for relevant tumor markers for improved patient selection an exploration of the proteome (the human proteins) could be fruitful. This paper critically reviews the use of 2-dimensional gel electrophoresis (2-DE) for proteome research. Additional steps such as image analysis and mass spectrometry are described. Techniques based on non-2-DE platforms: surface-enhanced laser desorption/ionization (SELDI), isotope coded affinity tags (ICAT) and array-based technologies are also summarized. Although labor-intensive and time-consuming, 2-DE is presently the most powerful method for analysis of cellular protein phenotype and may potentially reveal gene regulations that cannot be detected on a genetic level.

  18. External validation of a prognostic model predicting overall survival in metastatic castrate-resistant prostate cancer patients treated with abiraterone.

    PubMed

    Ravi, Praful; Mateo, Joaquin; Lorente, David; Zafeiriou, Zafeiris; Altavilla, Amelia; Ferraldeschi, Roberta; Sideris, Spyridon; Grist, Emily; Smith, Alan; Wong, Sophia; Bianchini, Diletta; Attard, Gerhardt; de Bono, Johann S

    2014-07-01

    A prognostic model was derived from the population of the COU-AA-301 phase 3 trial for metastatic castrate-resistant prostate cancer patients treated with abiraterone after docetaxel, and it stratifies patients into three risk groups based on clinical parameters. We validated this model in an independent cohort of patients treated with abiraterone after docetaxel outside a clinical trial (group A; n=94) and explored its utility in patients treated with abiraterone in the prechemotherapy setting (group B; n=64). For group A, median overall survival (mOS) was significantly different across the three prognostic groups (good: n=39, mOS: 21.8 mo; intermediate: n=44, mOS: 10.6 mo; poor: n=7, mOS: 6.8 mo; p<0.001; area under the curve [AUC]: 0.71). Analysis of group B confirmed the ability of the model to prognosticate for survival in the prechemotherapy setting: (good: n=44, mOS: 45.6 mo; intermediate or poor: n=20, mOS: 34.5 mo; p=0.042; AUC: 0.61). These results serve to validate the prognostic model in an independent population treated with abiraterone after docetaxel and support clinical implementation of the score. Calibration of the model was poorer in patients receiving abiraterone prechemotherapy. Prospective evaluation of this model in clinical trials is needed.

  19. TRICHOMONOSIS AND SUBSEQUENT RISK OF PROSTATE CANCER IN THE PROSTATE CANCER PREVENTION TRIAL

    PubMed Central

    Sutcliffe, Siobhan; Alderete, John F.; Till, Cathee; Goodman, Phyllis J.; Hsing, Ann W.; Zenilman, Jonathan M.; De Marzo, Angelo M.; Platz, Elizabeth A.

    2009-01-01

    We previously observed a positive association between a history of trichomonosis, a sexually transmitted infection caused by the protozoan, Trichomonas vaginalis, and prostate cancer risk in the Health Professionals Follow-up Study. To determine the reproducibility of this finding, we conducted a second, prospective investigation of trichomonosis and prostate cancer in the Prostate Cancer Prevention Trial. Participants were men ≥55 years of age with no evidence of prostate cancer at enrollment (n=18,882). Men were screened annually for prostate cancer, and if not diagnosed during the trial, were offered an end-of-study prostate biopsy. Cases were a sample of men diagnosed with prostate cancer on any biopsy after visit 2 or on their end-of-study biopsy (n=616). Controls were men not diagnosed with prostate cancer during the trial or on their end-of-study biopsy (n=616). Controls were frequency-matched to cases by age, treatment arm, and family history of prostate cancer. Serum from visit 2 was tested for anti-T. vaginalis IgG antibodies. No association was observed between T. vaginalis serostatus and prostate cancer. 21.5% of cases and 24.8% of controls had low seropositivity, and 15.2% and 15.0% had high seropositivity. Compared to seronegative men, the odds ratio of prostate cancer for men with low seropositivity was 0.83 (95% confidence interval (CI): 0.63–1.09), and that for men with high seropositivity was 0.97 (95% CI: 0.70–1.34). Given the original strong biologic rationale and potential for prevention, additional studies are warranted to help resolve discrepancies between study findings, and further investigate this hypothesis from a variety of different approaches. PMID:19117055

  20. Updates of prostate cancer staging: Prostate-specific membrane antigen

    PubMed Central

    Lamb, Alastair; Nair, Rajesh; Geurts, Nicolas; Mitchell, Catherine; Lawrentschuk, Nathan L; Moon, Daniel A; Murphy, Declan G

    2016-01-01

    The ability to accurately stage prostate cancer in both the primary and secondary staging setting can have a major impact on management. Until recently radiological staging has relied on computer tomography, magnetic resonance imaging, and nuclear bone scans to evaluate the extent of disease. However, the utility of these imaging technologies has been limited by their sensitivity and specificity especially in detecting early recurrence. Functional imaging using positron-emission tomography with a radiolabeled ligand targeted to prostate-specific membrane antigen has transformed the prostate cancer imaging landscape. Initial results suggest that it is a substantial improvement over conventional imaging in the setting of recurrence following primary therapy by having a superior ability to detect disease and to do so at an earlier stage. Additionally, it appears that the benefits seen in the secondary staging setting may also exist in the primary staging setting. PMID:27995218

  1. 75 FR 54453 - National Prostate Cancer Awareness Month, 2010

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-07

    ... Documents#0;#0; ] Proclamation 8552 of August 31, 2010 National Prostate Cancer Awareness Month, 2010 By the... the last decade, prostate cancer is still the second leading cause of cancer deaths among men in the United States. This year alone, nearly 218,000 men will be diagnosed with prostate cancer, and more...

  2. Genetics of Prostate Cancer (PDQ®)—Health Professional Version

    Cancer.gov

    Expert-reviewed information summary about the genetics of prostate cancer, including information about specific genes and family cancer syndromes. The summary also contains information about screening for prostate cancer and research aimed at prevention of this disease. Psychosocial issues associated with genetic testing and counseling of individuals who may have hereditary prostate cancer syndrome are also discussed.

  3. Management of Clinically Localized Prostate Cancer

    PubMed Central

    Lepor, Herbert

    2004-01-01

    Critics of screening have stated that early detection of prostate cancer does not necessarily reflect a diminishing death rate from the disease. However, several recent reports have demonstrated that the death rate from prostate cancer is decreasing, representing the most compelling validation for aggressive screening. Prostate cancer can be halted only if there is no evidence of systemic or regional metastases and the disease is confined to the surgical field or the radiation template. Surgeons and radiation oncologists must make a concerted effort to exclude men with regional and systemic metastases who are unlikely to benefit from treatment. With the widespread acceptance of prostate-specific antigen screening, a greater proportion of men are being diagnosed with clinically localized prostate cancer. Both radical prostatectomy and radiation therapy are able to halt disease spread in this significant subset of men, but survival outcomes indicate that radical prostatectomy is a more reliable treatment than radiation therapy for clinically localized prostate cancer. Overall, the immediate treatment-related morbidity of radical prostatectomy and radiation therapy in the modern era is quite low. Radical prostatectomy and radiation therapy appear to have a similar impact on continence and erectile function. There is a need for neoadjuvant and adjuvant therapies that can be utilized in those cases where radical prostatectomy and radiation are less likely to completely eradicate or destroy the cancer. PMID:16985859

  4. Radioisotopes in management of metastatic prostate cancer

    PubMed Central

    Raval, Amar; Dan, Tu D.; Williams, Noelle L.; Pridjian, Andrew; Den, Robert B.

    2016-01-01

    Introduction: Metastatic prostate cancer continues to be a leading cause of morbidity and mortality in men with prostate cancer. Over the last decade, the treatment landscape for patients with castrate-resistant disease has drastically changed, with several novel agents demonstrating an improvement in overall survival in large, multi-institutional randomized trials. Traditional treatment with radioisotopes has largely been in the palliative setting. However, the first in class radiopharmaceutical radium-223 has emerged as the only bone-directed treatment option demonstrating an improvement in overall survival. Methods: Medline publications from 1990 to 2016 were searched and reviewed to assess the use of currently approved radioisotopes in the management of prostate cancer including emerging data regarding integration with novel systemic therapies. New positron emission tomography-based radiotracers for advanced molecular imaging of prostate cancer were also queried. Results: Radioisotopes play a crucial role in the diagnosis and treatment of prostate cancer in the definitive and metastatic setting. Molecular imaging of prostate cancer and theranostics are currently being investigated in the clinical arena. Conclusions: The use of modern radioisotopes in selected patients with mCRPC is associated with improvements in overall survival, pain control, and quality of life. PMID:27843209

  5. Prostate cancer and diet: food for thought?

    PubMed

    Hori, Satoshi; Butler, Elizabeth; McLoughlin, John

    2011-05-01

    • There is now increasing evidence that diet plays a major role in prostate cancer biology and tumorigenesis. • In a health conscious society, it is becoming increasingly common for Urologists to be asked about the impact of diet on prostate cancer. • In the present review, we explore the current evidence for the role of different dietary components and its' effect on prostate cancer prevention and progression. • A literature search was conducted using PubMed® to identify key studies. • There was some evidence to suggest that green tea, isoflavones, lycopenes, cruciferous vegetables and omega 3 polyunsaturated fatty acid intake to be beneficial in the prevention and/or progression of prostate cancer. • There was also evidence to suggest that a high total fat, meat (especially well cooked) and multivitamin intake may be associated with an increased risk of developing prostate cancer. • To date publications have been highly heterogeneous and variable in quality and design. More robust, high quality research trials are needed to help us understand the complex relationship between diet and prostate cancer.

  6. Molecular targets of selenium in prostate cancer prevention (Review).

    PubMed

    Abdulah, Rizky; Kobayashi, Kenji; Yamazaki, Chiho; Koyama, Hiroshi

    2011-08-01

    Prostate cancer is one of the leading causes of cancer-related deaths among males. Although use of the micro-nutrient selenium in prostate cancer clinical trials is limited, the outcomes indicate that selenium is a promising treatment. Furthermore, selenium inhibits prostate cancer through multiple mechanisms, and it is beneficial in controlling the development of this disease. This review highlights the latest epidemiological and biomolecular research on selenium in prostate cancer, as well as its prospects for future clinical use.

  7. Hypoxia, notch signalling, and prostate cancer.

    PubMed

    Marignol, Laure; Rivera-Figueroa, Karla; Lynch, Thomas; Hollywood, Donal

    2013-07-01

    The notch signalling pathway is involved in differentiation, proliferation, angiogenesis, vascular remodelling, and apoptosis. Deregulated expression of notch receptors, ligands, and targets is observed in many solid tumours, including prostate cancer. Hypoxia is a common feature of prostate tumours, leading to increased gene instability, reduced treatment response, and increased tumour aggressiveness. The notch signalling pathway is known to regulate vascular cell fate and is responsive to hypoxia-inducible factors. Evidence to date suggests similar, therapeutically exploitable, behaviour of notch-activated and hypoxic prostate cancer cells.

  8. [An unusual presentation of prostate cancer].

    PubMed

    Joual, A; Rabii, R; Aboutaeib, R; el Moussaoui, A; Benjelloun, S

    1996-01-01

    The authors report an uncommon case of a 74-year old man with prostatic cancer revealed by pelvic mass. Ultrasound exam and CT-scan showed a bilateral laterorectal mass with high density. Presence of such a mass in an old patient is very suggestive of lymph nodes than retroperitoneal tumor. Serum prostate specific antigen (PSA) is rather helpful in such conditions. Biopsy of the mass allows confirmation of the prostatic cancer diagnosis. Bilateral Surgical pulpectomy is performed in combination with oral hormonal therapy. Follow-up after 6 months showed a good course or ultrasound exam and PSA level.

  9. The politics of prostate cancer screening.

    PubMed

    Kaffenberger, Samuel D; Penson, David F

    2014-05-01

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

  10. Family history and prostate cancer risk.

    PubMed

    Lesko, S M; Rosenberg, L; Shapiro, S

    1996-12-01

    The authors examined the relation between family history of prostate cancer and the risk of this cancer in a population-based case-control study conducted in Massachusetts between December 1992 and October 1994. Cases were all incident cases of prostate cancer in men younger than 70 years (n = 563); controls were men with no history of the disease matched to the cases on age and town of residence (n = 703). Prostate cancer risk was increased among men who reported a history of this cancer in either their fathers or brothers (odds ratio (OR) = 2.3, 95% confidence interval (CI) 1.7-3.3). Risk varied with the number of relatives affected and their relationship to the case. For a history of prostate cancer in one relative, the OR was 2.2 (95% CI 1.5-3.2); if two or more relatives were affected, it was 3.9 (95% CI 1.7-5.2). For prostate cancer in the father, the OR was 1.9 (95% CI 1.2-3.0); for prostate cancer in a brother, it was 3.0 (95% CI 1.8-4.9). Risk was inversely related to the subject's age and to age at diagnosis of prostate cancer in his affected relative. Among probands younger than 60 years, the OR was 5.3 (95% CI 2.5-12); for those 60-64 years of age, the OR was 2.7 (95% CI 1.3-5.5); and for those 65 years of age and older, the OR was 1.6 (95% CI 1.0-2.5). For prostate cancer diagnosed in a relative before age 65, the OR was 4.1 (95% CI 2.3-7.3); for detection of the disease after age 74, the OR was 0.76 (95% CI 0.38-1.5). The association was present both among men with local and advanced stage disease and among men whose prostate cancer was detected either by screening or because of symptoms. These data provide evidence that after controlling for diet and other potential confounders, familial factors are significantly associated with the risk of prostate cancer.

  11. Stereotactic Body Radiation Therapy in Treating Patients With Metastatic Breast Cancer, Non-small Cell Lung Cancer, or Prostate Cancer

    ClinicalTrials.gov

    2016-06-17

    Male Breast Carcinoma; Prostate Adenocarcinoma; Recurrent Breast Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Prostate Carcinoma; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Prostate Cancer

  12. Actions of estrogens and endocrine disrupting chemicals on human prostate stem/progenitor cells and prostate cancer risk.

    PubMed

    Hu, Wen-Yang; Shi, Guang-Bin; Hu, Dan-Ping; Nelles, Jason L; Prins, Gail S

    2012-05-06

    Estrogen reprogramming of the prostate gland as a function of developmental exposures (aka developmental estrogenization) results in permanent alterations in structure and gene expression that lead to an increased incidence of prostatic lesions with aging. Endocrine disrupting chemicals (EDCs) with estrogenic activity have been similarly linked to an increased prostate cancer risk. Since it has been suggested that stem cells and cancer stem cells are potential targets of cancer initiation and disease management, it is highly possible that estrogens and EDCs influence the development and progression of prostate cancer through reprogramming and transforming the prostate stem and early stage progenitor cells. In this article, we review recent literature highlighting the effects of estrogens and EDCs on prostate cancer risk and discuss recent advances in prostate stem/progenitor cell research. Our laboratory has recently developed a novel prostasphere model using normal human prostate stem/progenitor cells and established that these cells express estrogen receptors (ERs) and are direct targets of estrogen action. Further, using a chimeric in vivo prostate model derived from these normal human prostate progenitor cells, we demonstrated for the first time that estrogens initiate and promote prostatic carcinogenesis in an androgen-supported environment. We herein discuss these findings and highlight new evidence using our in vitro human prostasphere assay for perturbations in human prostate stem cell self-renewal and differentiation by natural steroids as well as EDCs. These findings support the hypothesis that tissue stem cells may be direct EDC targets which may underlie life-long reprogramming as a consequence of developmental and/or transient adult exposures.

  13. The systemic delivery of an oncolytic adenovirus expressing decorin inhibits bone metastasis in a mouse model of human prostate cancer

    SciTech Connect

    Xu, Weidong; Neill, Thomas; Yang, Yuefeng; Hu, Zebin; Cleveland, Elyse; Wu, Ying; Hutten, Ryan; Xiao, Xianghui; Stock, Stuart R.; Shevrin, Daniel; Kaul, Karen; Brendler, Charles; Iozzo, Renato V.; Seth, Prem

    2014-12-11

    In an effort to develop a new therapy for prostate cancer bone metastases, we have created Ad.dcn, a recombinant oncolytic adenovirus carrying the human decorin gene. Infection of PC-3 and DU-145, the human prostate tumor cells, with Ad.dcn or a non-replicating adenovirus Ad(E1-).dcn resulted in decorin expression; Ad.dcn produced high viral titers and cytotoxicity in human prostate tumor cells. Adenoviral-mediated decorin expression inhibited Met, the Wnt/β- catenin signaling axis, vascular endothelial growth factor A, reduced mitochondrial DNA levels, and inhibited tumor cell migration. To examine the anti-tumor response of Ad.dcn, PC-3-luc cells were inoculated in the left heart ventricle to establish bone metastases in nude mice. Ad.dcn, in conjunction with control replicating and non-replicating vectors were injected via tail vein. The real-time monitoring of mice, once a week, by bioluminescence imaging and X-ray radiography showed that Ad.dcn produced significant inhibition of skeletal metastases. Analyses of the mice at the terminal time point indicated a significant reduction in the tumor burden, osteoclast number, serum TRACP 5b levels, osteocalcin levels, hypercalcemia, inhibition of cancer cachexia, and an increase in the animal survival. Finally, based on these studies, we believe that Ad.dcn can be developed as a potential new therapy for prostate cancer bone metastasis.

  14. The systemic delivery of an oncolytic adenovirus expressing decorin inhibits bone metastasis in a mouse model of human prostate cancer

    DOE PAGES

    Xu, Weidong; Neill, Thomas; Yang, Yuefeng; ...

    2014-12-11

    In an effort to develop a new therapy for prostate cancer bone metastases, we have created Ad.dcn, a recombinant oncolytic adenovirus carrying the human decorin gene. Infection of PC-3 and DU-145, the human prostate tumor cells, with Ad.dcn or a non-replicating adenovirus Ad(E1-).dcn resulted in decorin expression; Ad.dcn produced high viral titers and cytotoxicity in human prostate tumor cells. Adenoviral-mediated decorin expression inhibited Met, the Wnt/β- catenin signaling axis, vascular endothelial growth factor A, reduced mitochondrial DNA levels, and inhibited tumor cell migration. To examine the anti-tumor response of Ad.dcn, PC-3-luc cells were inoculated in the left heart ventricle tomore » establish bone metastases in nude mice. Ad.dcn, in conjunction with control replicating and non-replicating vectors were injected via tail vein. The real-time monitoring of mice, once a week, by bioluminescence imaging and X-ray radiography showed that Ad.dcn produced significant inhibition of skeletal metastases. Analyses of the mice at the terminal time point indicated a significant reduction in the tumor burden, osteoclast number, serum TRACP 5b levels, osteocalcin levels, hypercalcemia, inhibition of cancer cachexia, and an increase in the animal survival. Finally, based on these studies, we believe that Ad.dcn can be developed as a potential new therapy for prostate cancer bone metastasis.« less

  15. Prostatic Fatty Acids and Cancer Recurrence Following Radical Prostatectomy for Early-Stage Prostate Cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: Results from some observational studies suggest that diet and energy balance influence the clinical course of early-stage prostate cancer. To evaluate possible mechanisms, we prospectively examined the relation between prostatic concentrations of fatty acids at diagnosis and cancer recurr...

  16. Update: Immunological Strategies for Prostate Cancer

    PubMed Central

    Antonarakis, Emmanuel S.

    2014-01-01

    Prostate cancer is the second most common cause of cancer-related death in US men. Along with initial therapy using surgery, radiotherapy, or cryotherapy, hormonal therapy is the mainstay of treatment. For men with advanced (metastatic) disease, docetaxel-based chemotherapy is US Food and Drug Administration (FDA)-approved, and provides a significant survival advantage. This relative paucity of treatment options drives an ongoing quest for additional treatment modalities; among these is immunotherapy. The concept that prostate cancer is a malignancy that can be targeted by the immune system may seem counterintuitive; certainly kidney cancer and melanoma are more traditionally thought of as immune responsive cancers. However, prostate cancer arises in a relatively unique organ and may express a number of proteins (antigens) against which an immune response can be generated. More importantly, several of these agents have now demonstrated a significant survival benefit in randomized controlled clinical trials, and one agent in particular (Sipuleucel-T, Dendreon Corporation, Seattle, WA) could be FDA-approved in 2010. This update summarizes recent clinical developments in the field of prostate cancer immunotherapy, with a focus on dendritic cell vaccines, virus-based vaccines, DNA-based vaccines, and cell-based vaccines. In addition, the notion of agents that target immune checkpoints is introduced. Enthusiasm for prostate cancer immunotherapy is founded upon its potential to mediate targeted, specific, tumor cell destruction without significant systemic toxicity; however, this has yet to be fully realized in the clinical arena. PMID:20425628

  17. Update: immunological strategies for prostate cancer.

    PubMed

    Drake, Charles G; Antonarakis, Emmanuel S

    2010-05-01

    Prostate cancer is the second most common cause of cancer-related death in US men. Along with initial therapy using surgery, radiotherapy, or cryotherapy, hormonal therapy is the mainstay of treatment. For men with advanced (metastatic) disease, docetaxel-based chemotherapy is US Food and Drug Administration (FDA)-approved, and provides a significant survival advantage. This relative paucity of treatment options drives an ongoing quest for additional treatment modalities; among these is immunotherapy. The concept that prostate cancer is a malignancy that can be targeted by the immune system may seem counterintuitive; certainly kidney cancer and melanoma are more traditionally thought of as immune responsive cancers. However, prostate cancer arises in a relatively unique organ and may express a number of proteins (antigens) against which an immune response can be generated. More importantly, several of these agents have now demonstrated a significant survival benefit in randomized controlled clinical trials, and one agent in particular (Sipuleucel-T, Dendreon Corporation, Seattle, WA) could be FDA-approved in 2010. This update summarizes recent clinical developments in the field of prostate cancer immunotherapy, with a focus on dendritic cell vaccines, virus-based vaccines, DNA-based vaccines, and cell-based vaccines. In addition, the notion of agents that target immune checkpoints is introduced. Enthusiasm for prostate cancer immunotherapy is founded upon its potential to mediate targeted, specific, tumor cell destruction without significant systemic toxicity; however, this has yet to be fully realized in the clinical arena.

  18. PROSTATE REGULATION: MODELING ENDOGENOUS ...

    EPA Pesticide Factsheets

    ALTERATIONS IN PROSTATE WEIGHT AND HISTOPATHOLOGY ARE OBSERVED FOLLOWING IN UTERO, PUBERTAL AND ADULT EXPOSURES TO ANTIANDROGENS. ALTERATIONS IN PROSTATE WEIGHT AND HISTOPATHOLOGY ARE OBSERVED FOLLOWING IN UTERO, PUBERTAL AND ADULT EXPOSURES TO ANTIANDROGENS.

  19. [Immunotherapy: a therapeutic revolution against prostate cancer?].

    PubMed

    Pracht, Marc; Herrera, Fernanda; Tawadros, Thomas; Berthold, Dominik

    2013-05-22

    The interaction between the immune system and cancer was an area of research interest for several decades. The recent U.S. Food and Drug Administration approval of sipuleucel-T and ipilimumab stimulated broader interest in manipulating immunity to fight cancer. In the context of prostate cancer, the immunotherapy strategies under development are therapeutic vaccination strategies, such as sipuleucel-T and PROSTVAC-VF, or immune checkpoint blockade of CTLA-4. Improved understanding of the immune responses generated by the development of predictive biomarkers for patient selection will guide rational combinations of these treatments and provide new treatment options in prostate cancer.

  20. Genetic counseling for prostate cancer risk.

    PubMed

    Nieder, A M; Taneja, S S; Zeegers, M P A; Ostrer, H

    2003-03-01

    Major risk factors for developing prostate cancer, including positive family history and African-American ethnicity, can be quantified for genetic counseling. Factors increasing familial risk for prostate cancer are closer degree of kinship, number of affected relatives, and early age of onset (< 50 years) among the affected relatives. Genetic testing may be useful for modification of risk, but currently should be performed only within the context of a well-designed research study that will determine penetrance and genotype-phenotype correlation of specific mutations. Even in the absence of genetic testing, African-American men and men with a strong family history of prostate cancer may opt to initiate screening by prostate specific antigen (PSA) and digital rectal exam (DRE) screening at age 40.

  1. Chemotherapy of prostate cancer: present and future.

    PubMed

    Trump, Donald; Lau, Yiu-Keung

    2003-06-01

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

  2. Prostate cancer immunology: biology, therapeutics, and challenges.

    PubMed

    Webster, W Scott; Small, Eric J; Rini, Brian I; Kwon, Eugene D

    2005-11-10

    A number of recently developed and promising approaches to antitumoral immunotherapy are being investigated as potential treatments for advanced prostate cancer. These approaches largely revolve around strategies to increase antigen-specific T-cell activation against prostate tumors as well as precise manipulations of critical co-regulatory receptors that help to maintain and prolong the activity of antigen-presenting cells and T cells that are capable of mediating tumor regression. Herein, we describe the experience with the most recent and promising approaches pertaining to prostate cancer immunotherapy. Additionally, we discuss the mechanistic basis for these approaches as well as current limitations that must still be addressed in order to propel immunotherapy into the forefront of prostate cancer treatment.

  3. Anti-cancer activity of curcumin loaded nanoparticles in prostate cancer

    PubMed Central

    Yallapu, Murali M.; Khan, Sheema; Maher, Diane M.; Ebeling, Mara C.; Sundram, Vasudha; Chauhan, Neeraj; Ganju, Aditya; Balakrishna, Swati; Gupta, Brij K.; Zafar, Nadeem; Jaggi, Meena; Chauhan, Subhash C.

    2014-01-01

    Prostate cancer is the most commonly diagnosed cancer disease in men in the Unites States and its management remains challenge in everyday oncology practice. Thus, advanced therapeutic strategies are required to treat prostate cancer patients. Curcumin (CUR) is a promising anticancer agent for various cancer types. The objective of this study was to evaluate therapeutic potential of novel poly(lactic-co-glycolic acid)- CUR nanoparticles (PLGA-CUR NPs) for prostate cancer treatment. Our results indicate that PLGA-CUR NPs efficiently internalize in prostate cancer cells and release biologically active CUR in cytosolic compartment of cells for effective therapeutic activity. Cell proliferation (MTS), clonogenic, and Western blot analyses reveal that PLGA-CUR NPs can effectively inhibit proliferation and colony formation ability of prostate cancer cells than free CUR. PLGA-CUR NPs showed superior tumor regression compared to CUR in xenograft mice. Further investigations reveal that PLGA-CUR NPs inhibit nuclear β-catenin and AR expression in cells and in tumor xenograft tissues. It also suppresses STAT3 and AKT phosphorylation and leads to apoptosis via inhibition of key anti-apoptotic proteins, MCL-1, Bcl-xL and caused induction of PARP cleavage. Additionally, PLGA-CUR NPs significant downregulation of oncogenic miR21 and up-regulation of miR-205 was observed with PLGA-CUR NPs treatment as determined by RT-PCR and in situ hybridization analyses. A superior anti-cancer potential was attained with PSMA antibody conjugated PLGA-CUR NPs in prostate cancer cells and a significant tumor targeting of 131I labelled PSMA antibody was achieved with PLGA-CUR NPs in prostate cancer xenograft mice model. In conclusion, PLGA-CUR NPs can significantly accumulate and exhibit superior anticancer activity in prostate cancer. PMID:25028336

  4. Multivariate normal tissue complication probability modeling of gastrointestinal toxicity after external beam radiotherapy for localized prostate cancer

    PubMed Central

    2013-01-01

    Background The risk of radio-induced gastrointestinal (GI) complications is affected by several factors other than the dose to the rectum such as patient characteristics, hormonal or antihypertensive therapy, and acute rectal toxicity. Purpose of this work is to study clinical and dosimetric parameters impacting on late GI toxicity after prostate external beam radiotherapy (RT) and to establish multivariate normal tissue complication probability (NTCP) model for radiation-induced GI complications. Methods A total of 57 men who had undergone definitive RT for prostate cancer were evaluated for GI events classified using the RTOG/EORTC scoring system. Their median age was 73 years (range 53–85). The patients were assessed for GI toxicity before, during, and periodically after RT completion. Several clinical variables along with rectum dose-volume parameters (Vx) were collected and their correlation to GI toxicity was analyzed by Spearman’s rank correlation coefficient (Rs). Multivariate logistic regression method using resampling techniques was applied to select model order and parameters for NTCP modeling. Model performance was evaluated through the area under the receiver operating characteristic curve (AUC). Results At a median follow-up of 30 months, 37% (21/57) patients developed G1-2 acute GI events while 33% (19/57) were diagnosed with G1-2 late GI events. An NTCP model for late mild/moderate GI toxicity based on three variables including V65 (OR = 1.03), antihypertensive and/or anticoagulant (AH/AC) drugs (OR = 0.24), and acute GI toxicity (OR = 4.3) was selected as the most predictive model (Rs = 0.47, p < 0.001; AUC = 0.79). This three-variable model outperforms the logistic model based on V65 only (Rs = 0.28, p < 0.001; AUC = 0.69). Conclusions We propose a logistic NTCP model for late GI toxicity considering not only rectal irradiation dose but also clinical patient-specific factors. Accordingly, the risk of G1

  5. Role of Nonreceptor Protein Kinase Ack 1 in Prostate Cancer

    DTIC Science & Technology

    2011-05-01

    cancer in vivo. 15. SUBJECT TERMS Prostate cancer, transgenic mice , mouse model 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT...1 In order to address task 1, prostates from PbAck1 mice and non-transgenic littermates were collected at multiple time points (12, 16, 24, 36, 48...our PbAck1;TgAPT121 bi-transgenic mice (Appendix Fig. 2). This result 8 validates the PbAck1;TgAPT121 bi-transgenic construct as a mouse model of

  6. Disruption of Prostate Epithelial Differentiation Pathways and Prostate Cancer Development

    PubMed Central

    Frank, Sander B.; Miranti, Cindy K.

    2013-01-01

    One of the foremost problems in the prostate cancer (PCa) field is the inability to distinguish aggressive from indolent disease, which leads to difficult prognoses and thousands of unnecessary surgeries. This limitation stems from the fact that the mechanisms of tumorigenesis in the prostate are poorly understood. Some genetic alterations are commonly reported in prostate tumors, including upregulation of Myc, fusion of Ets genes to androgen-regulated promoters, and loss of Pten. However, the specific roles of these aberrations in tumor initiation and progression are poorly understood. Likewise, the cell of origin for PCa remains controversial and may be linked to the aggressive potential of the tumor. One important clue is that prostate tumors co-express basal and luminal protein markers that are restricted to their distinct cell types in normal tissue. Prostate epithelium contains layer-specific stem cells as well as rare bipotent cells, which can differentiate into basal or luminal cells. We hypothesize that the primary oncogenic cell of origin is a transient-differentiating bipotent cell. Such a cell must maintain tight temporal and spatial control of differentiation pathways, thus increasing its susceptibility for oncogenic disruption. In support of this hypothesis, many of the pathways known to be involved in prostate differentiation can be linked to genes commonly altered in PCa. In this article, we review what is known about important differentiation pathways (Myc, p38MAPK, Notch, PI3K/Pten) in the prostate and how their misregulation could lead to oncogenesis. Better understanding of normal differentiation will offer new insights into tumor initiation and may help explain the functional significance of common genetic alterations seen in PCa. Additionally, this understanding could lead to new methods for classifying prostate tumors based on their differentiation status and may aid in identifying more aggressive tumors. PMID:24199173

  7. Nigerian foodstuffs with prostate cancer chemopreventive polyphenols

    PubMed Central

    2011-01-01

    Dietary polyphenols are antioxidants that can scavenge biological free radicals, and chemoprevent diseases with biological oxidation as their main etiological factor. In this paper, we review our laboratory data vis-ὰ-vis available literature on prostate cancer chemopreventive substances in Nigerian foodstuffs. Dacryodes edulis fruit, Moringa oleifera and Syzygium aromaticum contained prostate active polyphenols like ellagic acid, gallate, methylgallate, catechol, kaempferol quercetin and their derivatives. Also Canarium schweinfurthii Engl oil contained ten phenolic compounds and lignans, namely; catechol, p-hydroxybenzaldehyde, dihydroxyphenylacetic acid, tyrosol, p-hydroxybenzoic acid, dihydroxybenzoic acid, vanillic acid, phloretic acid, pinoresinol, secoisolariciresinol. In addition, tomatoes (Lycopersicon esculentum Mill) which contains the powerful antioxidant and anti-prostate cancer agent, lycopene; cabbage (Brassica oleracea) containing indole-3-carbinol; citrus fruits containing pectin; Soursop (Annona muricata) containing annonaceous acetogenins; soya beans (Glycine max) containing isoflavones; chilli pepper (Capsicum annuum) containing capsaicin, and green tea (Camellia sinensis) containing (-) epigallocatechin gallate (EGCG), (-) epicatechin, (-) epicatechin-3-gallate and (-) epigallocatechin -3-gallate which are widely reported to posses prostate cancer chemopreventive compounds are also grown in Nigeria and other African countries. Thus, the high incidence of prostate cancer among males of African extraction can be dramatically reduced, and the age of onset drastically increased, if the population at risk consumes the right kinds of foods in the right proportion, beginning early in life, especially as prostate cancer has a latency period of about 50 years. PMID:21992488

  8. Nigerian foodstuffs with prostate cancer chemopreventive polyphenols.

    PubMed

    Atawodi, Sunday Eneojo

    2011-09-23

    Dietary polyphenols are antioxidants that can scavenge biological free radicals, and chemoprevent diseases with biological oxidation as their main etiological factor. In this paper, we review our laboratory data vis-ὰ-vis available literature on prostate cancer chemopreventive substances in Nigerian foodstuffs. Dacryodes edulis fruit, Moringa oleifera and Syzygium aromaticum contained prostate active polyphenols like ellagic acid, gallate, methylgallate, catechol, kaempferol quercetin and their derivatives. Also Canarium schweinfurthii Engl oil contained ten phenolic compounds and lignans, namely; catechol, p-hydroxybenzaldehyde, dihydroxyphenylacetic acid, tyrosol, p-hydroxybenzoic acid, dihydroxybenzoic acid, vanillic acid, phloretic acid, pinoresinol, secoisolariciresinol. In addition, tomatoes (Lycopersicon esculentum Mill) which contains the powerful antioxidant and anti-prostate cancer agent, lycopene; cabbage (Brassica oleracea) containing indole-3-carbinol; citrus fruits containing pectin; Soursop (Annona muricata) containing annonaceous acetogenins; soya beans (Glycine max) containing isoflavones; chilli pepper (Capsicum annuum) containing capsaicin, and green tea (Camellia sinensis) containing (-) epigallocatechin gallate (EGCG), (-) epicatechin, (-) epicatechin-3-gallate and (-) epigallocatechin -3-gallate which are widely reported to posses prostate cancer chemopreventive compounds are also grown in Nigeria and other African countries. Thus, the high incidence of prostate cancer among males of African extraction can be dramatically reduced, and the age of onset drastically increased, if the population at risk consumes the right kinds of foods in the right proportion, beginning early in life, especially as prostate cancer has a latency period of about 50 years.

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

    DTIC Science & Technology

    2007-04-01

    in part - to it’s strong positive association with age.6,7 Benign prostatic hyperplasia , which is also highly associated with age, contributes to...prostate cancer risk. Moreover, benign prostatic hyperplasia (BPH), which is also strongly associated with age, can raise PSA levels and further muddy...contemporary referral series of men with prostate cancer. 60(4 Suppl 1):47-52, 2002 8. Fitzpatrick JM. The natural history of benign prostatic hyperplasia . BJU

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

    DTIC Science & Technology

    2006-10-01

    strong positive association with age.6,7 Benign prostatic hyperplasia , which is also highly associated with age, contributes to increased PSA levels and...prostate cancer risk. Moreover, benign prostatic hyperplasia (BPH), which is also strongly associated with age, can raise PSA levels and further muddy...contemporary referral series of men with prostate cancer. 60(4 Suppl 1):47-52, 2002 8. Fitzpatrick JM. The natural history of benign prostatic hyperplasia . BJU

  11. TPD52: A Novel Vaccine Target for Prostate Cancer

    DTIC Science & Technology

    2009-09-01

    Chinnaiyan AM and Rubin MA. (2006). Defining aggressive prostate cancer using a 12-gene model. Neoplasia 8: 59-68. 12. Scanlan MJ, Gout I, Gordon CM...Chromosomes Cancer 2000;29:48 –57. 20. Scanlan MJ, Gout I, Gordon CM, et al. Humoral immunity to human breast cancer: antigen definition and...Zhang XK, Halverson DO (1997) Characterization of human N8 protein. Oncogene 15:2577–2588 42. Scanlan MJ, Gout I, Gordon CM, Williamson B, Stockert E

  12. Radiosensitization in prostate cancer: mechanisms and targets

    PubMed Central

    2013-01-01

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

  13. Prostate cancer in men of African origin.

    PubMed

    McGinley, Kathleen F; Tay, Kae Jack; Moul, Judd W

    2016-02-01

    Men of African origin are disproportionately affected by prostate cancer: prostate cancer incidence is highest among men of African origin in the USA, prostate cancer mortality is highest among men of African origin in the Caribbean, and tumour stage and grade at diagnosis are highest among men in sub-Saharan Africa. Socioeconomic, educational, cultural, and genetic factors, as well as variations in care delivery and treatment selection, contribute to this cancer disparity. Emerging data on single-nucleotide-polymorphism patterns, epigenetic changes, and variations in fusion-gene products among men of African origin add to the understanding of genetic differences underlying this disease. On the diagnosis of prostate cancer, when all treatment options are available, men of African origin are more likely to choose radiation therapy or to receive no definitive treatment than white men. Among men of African origin undergoing surgery, increased rates of biochemical recurrence have been identified. Understanding differences in the cancer-survivorship experience and quality-of-life outcomes among men of African origin are critical to appropriately counsel patients and improve cultural sensitivity. Efforts to curtail prostate cancer screening will likely affect men of African origin disproportionately and widen the racial disparity of disease.

  14. Prostate Cancer Treatments Have Varying Side Effects, Study Shows

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_164200.html Prostate Cancer Treatments Have Varying Side Effects, Study Shows Even ' ... News) -- The long-term side effects of different prostate cancer treatments vary -- and knowing that may help men ...

  15. Anxiety May Lead to Unneeded Prostate Cancer Treatments

    MedlinePlus

    ... fullstory_163295.html Anxiety May Lead to Unneeded Prostate Cancer Treatments Researchers suggest that dealing with a patient's ... Jan. 27, 2017 (HealthDay News) -- Anxiety may prompt prostate cancer patients to opt for potentially unnecessary treatments, a ...

  16. Georgetown University and Hampton University Prostate Cancer Undergraduate Fellowship Program

    DTIC Science & Technology

    2014-10-01

    TITLE: Georgetown University and Hampton University Prostate Cancer Undergraduate Fellowship Program PRINCIPAL INVESTIGATOR: Anatoly...University Prostate Cancer Undergraduate Fellowship Program 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER

  17. Breast and Prostate Cancer Cohort Consortium (BPC3)

    Cancer.gov

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

  18. Prostate cancer incidence in men with self-reported prostatitis after 15 years of follow-up

    PubMed Central

    Vaarala, Markku H.; Mehik, Aare; Ohtonen, Pasi; Hellström, Pekka A.

    2016-01-01

    Controversy exists regarding a possible association between prostatitis and prostate cancer. To further evaluate the incidence of prostate cancer following prostatitis, a study of prostate cancer incidence in a cohort of Finnish men was performed. The original survey evaluating self-reported prostatitis was conducted in 1996–1997. A database review was conducted focusing on prostate cancer diagnoses in the cohort. In 2012, there were 13 (5.2%) and 27 (1.8%) prostate cancer cases among men with (n=251) and without (n=1,521) prostatitis symptoms, respectively. There were no significant differences in age, primary therapy distribution, prostate-specific antigen levels, Gleason score, clinical T-class at the time of prostate cancer diagnosis, or time lag between the original survey and prostate cancer diagnosis. The standardized incidence ratio (SIR) of prostate cancer was 1.16 [95% confidence interval (CI), 0.62–1.99] and 0.44 (95% CI, 0.29–0.64) among men with and without prostatitis symptoms, respectively. After 15 years of follow-up subsequent to self-reported prostatitis, no evident increase in incidence of prostate cancer was detected among Finnish men with prostatitis symptoms. The higher percentage of prostate cancer among men with prostatitis symptoms appears to be due to coincidentally low SIR of prostate cancer among men without prostatitis symptoms, and may additionally be due to increased diagnostic examinations. Further research is required to confirm this speculation. PMID:27446410

  19. Prostate cancer incidence in men with self-reported prostatitis after 15 years of follow-up.

    PubMed

    Vaarala, Markku H; Mehik, Aare; Ohtonen, Pasi; Hellström, Pekka A

    2016-08-01

    Controversy exists regarding a possible association between prostatitis and prostate cancer. To further evaluate the incidence of prostate cancer following prostatitis, a study of prostate cancer incidence in a cohort of Finnish men was performed. The original survey evaluating self-reported prostatitis was conducted in 1996-1997. A database review was conducted focusing on prostate cancer diagnoses in the cohort. In 2012, there were 13 (5.2%) and 27 (1.8%) prostate cancer cases among men with (n=251) and without (n=1,521) prostatitis symptoms, respectively. There were no significant differences in age, primary therapy distribution, prostate-specific antigen levels, Gleason score, clinical T-class at the time of prostate cancer diagnosis, or time lag between the original survey and prostate cancer diagnosis. The standardized incidence ratio (SIR) of prostate cancer was 1.16 [95% confidence interval (CI), 0.62-1.99] and 0.44 (95% CI, 0.29-0.64) among men with and without prostatitis symptoms, respectively. After 15 years of follow-up subsequent to self-reported prostatitis, no evident increase in incidence of prostate cancer was detected among Finnish men with prostatitis symptoms. The higher percentage of prostate cancer among men with prostatitis symptoms appears to be due to coincidentally low SIR of prostate cancer among men without prostatitis symptoms, and may additionally be due to increased diagnostic examinations. Further research is required to confirm this speculation.

  20. Risk of malignant melanoma in men with prostate cancer: Nationwide, population-based cohort study.

    PubMed

    Thomsen, Frederik B; Folkvaljon, Yasin; Garmo, Hans; Robinson, David; Loeb, Stacy; Ingvar, Christian; Lambe, Mats; Stattin, Pär

    2016-05-01

    An increased risk of malignant melanoma has been observed in men with prostate cancer. To assess potential shared risk factors and confounding factors, we analysed risk of melanoma in men with prostate cancer including information on tumor characteristics and demographics including socioeconomic status. In The Prostate Cancer data Base Sweden, risk of melanoma was assessed in a cohort of men with prostate cancer and in a comparison cohort of prostate-cancer free men. Data on prostate cancer risk category, melanoma stage, basal cell carcinoma, location of residency, and socioeconomic status were obtained from nationwide registers. Melanoma was diagnosed in 830/108,145 (0.78%) men with prostate cancer and in 3,699/556,792 (0.66%) prostate cancer-free men. In multivariable Cox regression models, men with prostate cancer had a significantly increased risk of melanoma (HR 1.18, 95% CI 1.09-1.27), and so had married men, men with high education and income, and men residing in southern Sweden. The strongest associations were observed for stage 0 melanoma in men with low-risk prostate cancer (HR 1.45, 1.14-1.86), high education (HR 1.87, 1.60-2.18) and top income (HR 1.61, 1.34-1.93), respectively, whereas there was no association between these factors and late-stage melanoma. Men with prostate cancer also had an increased risk of basal cell carcinoma (HR 1.18, 1.15-1.22). In conclusion, men with low-risk prostate cancer, high education, high income and residency in southern Sweden had an increased risk of early-stage melanoma.

  1. Computer model for photodynamic therapy of the prostate

    NASA Astrophysics Data System (ADS)

    Jankun, Jerzy; Zaim, Amjad; Jankun-Kelly, Monika; Keck, Rick W.; Selman, Steven H.

    2000-05-01

    Photodynamic therapy (PDT) is an emerging minimally invasive treatment that can be employed in many human diseases including prostate cancer. This treatment of human prostate cancer depends on the localization of a drug (photosensitizer) into the prostate. The photosensitizer is activated by high- energy laser light and the active drug destroys cancerous tissue. The success of PDT depends on precise placement of light diffusers in the prostate. Since the prostate is irregular in shape, with different dimensions, a transurethral light delivery that is circular in distribution cannot be used in most cases of carcinoma of the prostate. Sources of light and their spatial distribution must be tailored to each individual patient. More uniform, therapeutic light distribution can be achieved by interstitial light irradiation. In this case, the light is delivered by diffusers placed within the substance of the prostate parallel to the urethra at a distance optimized to deliver adequate levels of light and to create the desired photodynamic effect. For this reason, we are developing a computer program that can calculate the distribution of energy depending on the number of light sources placed in the prostate, their position in the gland, the dimension of the prostate, and the attenuation coefficient. A patient's three-dimensional prostate model is built based on ultrasound images. Then the program is being designated to predict the best set of parameters and position of light diffusers in space, displays them in graphical form or in numerical form. The program is amenable for interfacing with robotic treatment systems.

  2. A Prostate Cancer Model Build by a Novel SVM-ID3 Hybrid Feature Selection Method Using Both Genotyping and Phenotype Data from dbGaP

    PubMed Central

    Yücebaş, Sait Can; Aydın Son, Yeşim

    2014-01-01

    Through Genome Wide Association Studies (GWAS) many Single Nucleotide Polymorphism (SNP)-complex disease relations can be investigated. The output of GWAS can be high in amount and high dimensional, also relations between SNPs, phenotypes and diseases are most likely to be nonlinear. In order to handle high volume-high dimensional data and to be able to find the nonlinear relations we have utilized data mining approaches and a hybrid feature selection model of support vector machine and decision tree has been designed. The designed model is tested on prostate cancer data and for the first time combined genotype and phenotype information is used to increase the diagnostic performance. We were able to select phenotypic features such as ethnicity and body mass index, and SNPs those map to specific genes such as CRR9, TERT. The performance results of the proposed hybrid model, on prostate cancer dataset, with 90.92% of sensitivity and 0.91 of area under ROC curve, shows the potential of the approach for prediction and early detection of the prostate cancer. PMID:24651484

  3. JAGGED1 expression is associated with prostate cancer metastasis and recurrence.

    PubMed

    Santagata, Sandro; Demichelis, Francesca; Riva, Alberto; Varambally, Sooryanarayana; Hofer, Matthias D; Kutok, Jeffery L; Kim, Robert; Tang, Jeffery; Montie, James E; Chinnaiyan, Arul M; Rubin, Mark A; Aster, Jon C

    2004-10-01

    Recent studies suggest that NOTCH signaling can promote epithelial-mesenchymal transitions and augment signaling through AKT, an important growth and survival pathway in epithelial cells and prostate cancer in particular. Here we show that JAGGED1, a NOTCH receptor ligand, is significantly more highly expressed in metastatic prostate cancer as compared with localized prostate cancer or benign prostatic tissues, based on immunohistochemical analysis of JAGGED1 expression in human tumor samples from 154 men. Furthermore, high JAGGED1 expression in a subset of clinically localized tumors was significantly associated with recurrence, independent of other clinical parameters. These findings support a model in which dysregulation of JAGGED1 protein levels plays a role in prostate cancer progression and metastasis and suggest that JAGGED1 may be a useful marker in distinguishing indolent and aggressive prostate cancers.

  4. Association Between Cd Exposure and Risk of Prostate Cancer

    PubMed Central

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

    2016-01-01

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

  5. Zoledronic Acid Decreased Osteolysis But Not Bone Metastasis in a Nude Mouse Model of Canine Prostate Cancer With Mixed Bone Lesions

    PubMed Central

    Thudi, Nanda K.; Martin, Chelsea K.; Nadella, Murali V.P.; Fernandez, Soledad A.; Werbeck, Jillian L.; Pinzone, Joseph J.; Rosol, Thomas J.

    2010-01-01

    BACKGROUND Bone metastasis is the most common cause of morbidity and mortality in patients with advanced prostate cancer and is manifested primarily as mixed osteoblastic and osteolytic lesions. However, the mechanisms responsible for bone metastases in prostate cancer are not clearly understood, in part due to the lack of relevant in vivo models that mimic the clinical presentation of the disease in humans. We previously established a nude mouse model with mixed bone metastases using intracardiac injection of canine prostate cancer cells (Ace-1). In this study, we hypothesized that tumor-induced osteolysis promoted the incidence of bone metastases and osteoblastic activity. METHODS We studied the effect of inhibition of osteolysis with zoledronic acid (ZA) on the prevention and progression of Ace-1 bone metastases in nude mice using prophylactic and delayed treatment protocols. Bioluminescent imaging, radiography, and histopathological evaluation were performed to monitor the effect of ZA on the incidence, progression and nature of bone metastases. RESULTS Unexpectedly, there was no significant difference in tumor burden and the incidence of metastasis between control and treatment groups as detected by bioluminescent imaging and bone histomorphometry. However, radiographic and histopathological analysis showed a significant treatment-related decrease in osteolysis, but no effect on tumor-induced trabecular bone thickness in both treatment groups compared to controls. CONCLUSION Our results demonstrated that the incidence of prostate cancer bone metastases in vivo was not reduced by zoledronic acid even though zoledronic acid inhibited bone resorption and bone loss associated with the mixed osteoblastic/osteolytic bone metastases in the Ace-1 model. PMID:18461562

  6. Development and exploitation of a novel mutant androgen receptor modelling strategy to identify new targets for advanced prostate cancer therapy.

    PubMed

    O'Neill, Daniel; Jones, Dominic; Wade, Mark; Grey, James; Nakjang, Sirintra; Guo, Wenrui; Cork, David; Davies, Barry R; Wedge, Steve R; Robson, Craig N; Gaughan, Luke

    2015-09-22

    The persistence of androgen receptor (AR) signalling in castrate-resistant prostate cancer (CRPC) highlights the unmet clinical need for the development of more effective AR targeting therapies. A key mechanism of therapy-resistance is by selection of AR mutations that convert anti-androgens to agonists enabling the retention of androgenic signalling in CRPC. To improve our understanding of these receptors in advanced disease we developed a physiologically-relevant model to analyse the global functionality of AR mutants in CRPC. Using the bicalutamide-activated AR(W741L/C) mutation as proof of concept, we demonstrate that this mutant confers an androgenic-like signalling programme and growth promoting phenotype in the presence of bicalutamide. Transcriptomic profiling of AR(W741L) highlighted key genes markedly up-regulated by the mutant receptor, including TIPARP, RASD1 and SGK1. Importantly, SGK1 expression was found to be highly expressed in the KUCaP xenograft model and a CRPC patient biopsy sample both of which express the bicalutamide-activated receptor mutant. Using an SGK1 inhibitor, AR(W741L) transcriptional and growth promoting activity was reduced indicating that exploiting functional distinctions between receptor isoforms in our model may provide new and effective therapies for CRPC patients.

  7. Development and exploitation of a novel mutant androgen receptor modelling strategy to identify new targets for advanced prostate cancer therapy

    PubMed Central

    O'Neill, Daniel; Jones, Dominic; Wade, Mark; Grey, James; Nakjang, Sirintra; Guo, Wenrui; Cork, David; Davies, Barry R.; Wedge, Steve R.; Robson, Craig N.; Gaughan, Luke

    2015-01-01

    The persistence of androgen receptor (AR) signalling in castrate-resistant prostate cancer (CRPC) highlights the unmet clinical need for the development of more effective AR targeting therapies. A key mechanism of therapy-resistance is by selection of AR mutations that convert anti-androgens to agonists enabling the retention of androgenic signalling in CRPC. To improve our understanding of these receptors in advanced disease we developed a physiologically-relevant model to analyse the global functionality of AR mutants in CRPC. Using the bicalutamide-activated ARW741L/C mutation as proof of concept, we demonstrate that this mutant confers an androgenic-like signalling programme and growth promoting phenotype in the presence of bicalutamide. Transcriptomic profiling of ARW741L highlighted key genes markedly up-regulated by the mutant receptor, including TIPARP, RASD1 and SGK1. Importantly, SGK1 expression was found to be highly expressed in the KUCaP xenograft model and a CRPC patient biopsy sample both of which express the bicalutamide-activated receptor mutant. Using an SGK1 inhibitor, ARW741L transcriptional and growth promoting activity was reduced indicating that exploiting functional distinctions between receptor isoforms in our model may provide new and effective therapies for CRPC patients. PMID:26267320

  8. Role of GGAP/PIKE-A in prostate cancer progression

    DTIC Science & Technology

    2009-05-01

    isoform which also contains a COOH-terminal Arf-GAP domain and two ankyrin repeats . Both of these proteins can bind PI3-K via their proline-rich...may contribute to increased activity of GGAP2 in prostate cancer. In summary, GGAP2 may promote prostate cancer growth and progression via...that they may contribute to the functions of GGAP2 in prostate cancer. In summary, GGAP2 may promote prostate cancer growth and progression via

  9. Oxidative Stress, DNA Repair, and Prostate Cancer Risk

    DTIC Science & Technology

    2011-08-01

    have concluded that DRC is not a risk factor for prostate cancer microRNA prostate cancer Hua.Zhao@RoswellPark.org Table of Contents...known and suspected risk factors for prostate cancer are associated with elevated levels of reactive oxygen species (ROS) (advancing age, inflammation...association between DNA repair capacity and prostate cancer risk might be due to the fact of using surrogate tissues , not the target tissues . In this study

  10. Lateral biopsies added to the traditional sextant prostate biopsy pattern increases the detection rate of prostate cancer.

    PubMed

    Bauer, J J; Zeng, J; Zhang, W; McLeod, D G; Sesterhenn, I A; Connelly, R R; Mun, S K; Moul, J W

    2000-07-01

    Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error and data based upon whole-mounted step-sectioned radical prostatectomy specimens using a three-dimensional computer-assisted prostate biopsy simulator suggests that an increased detection rate is possible using laterally placed biopsies. The simulated 10-core biopsy pattern (traditional sextant biopsy cores and four laterally placed biopsies in the right and left apex and mid portion of the prostate gland) was shown to be superior to the traditional sextant biopsy. The objective of this pilot study was to confirm the higher prostate cancer detection rate obtained using the 10-core biopsy pattern in patients. We reviewed data on 35 consecutive patients with a pathologic diagnosis of prostate cancer biopsied by a single urologist using the 10-core biopsy pattern. The frequency of positive biopsy was determined for each core. Additionally, the sextant and 10-core prostate biopsy patterns were compared with respect to prostate cancer detection rate. Of the 35 patients diagnosed with prostate cancer, 54.3%(19/35) were diagnosed by the sextant biopsy only. The 10-core pattern resulted in an additional 45.7%(16/35) of patients being diagnosed solely with the laterally placed biopsies. The laterally placed biopsies had the highest frequency of positive biopsies when compared to the sextant cores. In conclusion, biopsy protocols that use laterally placed biopsies based upon a five region anatomical model are superior to the routinely used sextant prostate biopsy pattern. Prostate Cancer and Prostatic Diseases (2000) 3, 43-46

  11. Prostate cancer epigenetics and its clinical implications.

    PubMed

    Yegnasubramanian, Srinivasan

    2016-01-01

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

  12. Prostate cancer epigenetics and its clinical implications

    PubMed Central

    Yegnasubramanian, Srinivasan

    2016-01-01

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

  13. [The treatment options for localized prostate cancer].

    PubMed

    Livne, Pinhas M

    2006-01-01

    Prostate cancer is a very common tumor in men. Today the disease is very often diagnosed early because of an elevated PSA without symptoms and the disease is localized to the prostate. Patients with prostate cancer can be divided into 3 subgroups for the carcinoma: favorable, moderate, and poorly. The grouping depends mainly on the Gleason score of the prostate biopsy. According to the Gleason score, favorable cancer is up to score 6 (3 + 3), moderate score 7, and poor--Gleason score 8-10. The other favorable clinical factors are PSA < 10 ng/ml, and clinical stage by DRE of T1C or T2 (no nodule or palpable nodule not extending beyond the prostatic capsule). The treatment options for cure when the prostate cancer is localized are either radical prostatectomy or radiotherapy (external or brachytherapy or combination). Each of these therapies has side effects and each has advantages and disadvantages. Sometimes the treatment choice is not for cure and the options are hormonal treatment or watchful waiting. Twenty to 30% of the patients treated for cure may fail the treatment and have elevation of PSA without any clinical symptoms, or signs of local recurrence or distant spread. Some of these patients with biochemical failure may be cured by salvage treatment: radiotherapy after radical prostatectomy and salvage radical prostatectomy or cryotherapy following failure of radiotherapy.

  14. How Precisely Can Prostate Cancer Be Managed?

    PubMed Central

    2016-01-01

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

  15. Cuprous oxide nanoparticles inhibit prostate cancer by attenuating the stemness of cancer cells via inhibition of the Wnt signaling pathway

    PubMed Central

    Wang, Ye; Yang, Qi-Wei; Yang, Qing; Zhou, Tie; Shi, Min-Feng; Sun, Chen-Xia; Gao, Xiu-Xia; Cheng, Yan-Qiong; Cui, Xin-Gang; Sun, Ying-Hao

    2017-01-01

    Disordered copper metabolism plays a critical role in the development of various cancers. As a nanomedicine containing copper, cuprous oxide nanoparticles (CONPs) exert ideal antitumor pharmacological effects in vitro and in vivo. Prostate cancer is a frequently diagnosed male malignancy prone to relapse, and castration resistance is the main reason for endocrine therapy failure. However, whether CONPs have the potential to treat castration-resistant prostate cancer is still unknown. Here, using the castration-resistant PC-3 human prostate cancer cell line as a model, we report that CONPs can selectively induce apoptosis and inhibit the proliferation of cancer cells in vitro and in vivo without affecting normal prostate epithelial cells. CONPs can also attenuate the stemness of cancer cells and inhibit the Wnt signaling pathway, both of which highlight the great potential of CONPs as a new clinical castration-resistant prostate cancer therapy.

  16. Satisfaction with Information Used to Choose Prostate Cancer Treatment

    PubMed Central

    Gilbert, Scott M.; Sanda, Martin G.; Dunn, Rodney L.; Greenfield, Thomas K.; Hembroff, Larry; Klein, Eric; Saigal, Christopher S.; Pisters, Louis; Michalski, Jeff; Sandler, Howard M.; Litwin, Mark S.; Wei, John T.

    2014-01-01

    Purpose After being diagnosed with prostate cancer men must assimilate information regarding the cancer. Satisfaction with information reflects the evaluation of information sources used before treatment to select a therapy. We describe the use and helpfulness of several information sources available to prostate cancer survivors. We also identified factors associated with satisfaction with information. Materials and Methods A total of 1,204 men with newly diagnosed prostate cancer were enrolled in the prospective, multicenter Prostate Cancer Outcomes and Satisfaction with Therapy Quality Assessment study. The validated satisfaction with information domain of the Service Satisfaction Scale-Cancer was administered to subjects 2 months after treatment. The relationship between several factors, such as demographics, socioeconomic factors, cancer severity and types of information sources, and satisfaction with information were evaluated using multiple regression. Results Sources of information endorsed by subjects varied by race, education and study site. The most helpful sources were treatment description by the treating physician (33.1%), Internet sites (18.9%) and books (18.1%). In multiple variable models patient age (p = 0.005) and information provided by the physician regarding outcomes in their patients (p = 0.01) were independently associated with patient satisfaction with the information provided. Conclusions Various information sources were used and endorsed as helpful by subjects, although results for physician patients was the only source independently associated with satisfaction with information. Providing patients with information about possible or expected courses of care and outcomes may improve satisfaction. PMID:24333514

  17. Preclinical and clinical development of DNA vaccines for prostate cancer.

    PubMed

    Colluru, V T; Johnson, Laura E; Olson, Brian M; McNeel, Douglas G

    2016-04-01

    Prostate cancer is the most commonly diagnosed cancer in the United States. It is also the second leading cause of cancer-related death in men, making it one of the largest public health concerns today. Prostate cancer is an ideal disease for immunotherapies because of the generally slow progression, the dispensability of the target organ in the patient population, and the availability of several tissue-specific antigens. As such, several therapeutic vaccines have entered clinical trials, with one autologous cellular vaccine (sipuleucel-T) recently gaining Food and Drug Administration approval after demonstrating overall survival benefit in randomized phase III clinical trials. DNA-based vaccines are safe, economical, alternative "off-the-shelf" approaches that have undergone extensive evaluation in preclinical models. In fact, the first vaccine approved in the United States for the treatment of cancer was a DNA vaccine for canine melanoma. Several prostate cancer-specific DNA vaccines have been developed in the last decade and have shown promising results in early phase clinical trials. This review summarizes anticancer human DNA vaccine trials, with a focus on those conducted for prostate cancer. We conclude with an outline of special considerations important for the development and successful translation of DNA vaccines from the laboratory to the clinic.

  18. Extremely Early Diagnostic Test for Prostate Cancer

    SciTech Connect

    James, Veronica Jean

    2011-11-17

    This article reports the results of a blinded fiber diffraction study of skin samples taken from TRAMP mice and age-matched controls to determine whether changes noted in fiber diffraction studies of human skin were present in these TRAMP mice studies. These mice are bred to progress to Gleeson Type 3 to Type 5 prostate cancer. Small strips, 1 mm x 5 mm, cut from the mouse skin samples were loaded into cells in the same way as human samples and slightly stretched to remove the crimp. They remained fully hydrated throughout exposure to the synchrotron beam. The added change that was reported for prostate cancer in 2009 was obtained for all TRAMP mice samples, indicating that this change can be read as High Grade Cancer in human diagnostic tests. These changes were evident for all 3 and 7 week old TRAMP mice samples but not for any of the control samples. This indicates that the changes in the fibre diffraction patterns appear much earlier than in any other available prostate cancer diagnostic test, as none of these can verify the presence of prostate cancer in the TRAMP mice before 10 weeks of age. The fiber diffraction test is therefore the most accurate and earliest test for high grade prostate cancer.

  19. Risk stratification in prostate cancer screening.

    PubMed

    Roobol, Monique J; Carlsson, Sigrid V

    2013-01-01

    Screening for prostate cancer is a controversial topic within the field of urology. The US Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial did not demonstrate any difference in prostate-cancer-related mortality rates between men screened annually rather than on an 'opportunistic' basis. However, in the world's largest trial to date--the European Randomised Study of Screening for Prostate Cancer--screening every 2-4 years was associated with a 21% reduction in prostate-cancer-related mortality rate after 11 years. Citing the uncertain ratio between potential harm and potential benefit, the US Preventive Services Task Force recently recommended against serum PSA screening. Although this ratio has yet to be elucidated, PSA testing--and early tumour detection--is undoubtedly beneficial for some individuals. Instead of adopting a 'one size fits all' approach, physicians are likely to perform personalized risk assessment to minimize the risk of negative consequences, such as anxiety, unnecessary testing and biopsies, overdiagnosis, and overtreatment. The PSA test needs to be combined with other predictive factors or be used in a more thoughtful way to identify men at risk of symptomatic or life-threatening cancer, without overdiagnosing indolent disease. A risk-adapted approach is needed, whereby PSA testing is tailored to individual risk.

  20. Use of 1,25α dihydroxyvitamin D3 as a cryosensitizing agent in a murine prostate cancer model.

    PubMed

    Santucci, K L; Snyder, K K; Baust, J M; Van Buskirk, R G; Mouraviev, V; Polascik, T J; Gage, A A; Baust, J G

    2011-06-01

    Cryotherapy has emerged as a primary treatment option for prostate cancer (CaP); however, incomplete ablation in the periphery of the cryogenic lesion can lead to recurrence. Accordingly, we investigated the use of a non-toxic adjunctive agent, vitamin D3 (VD3), with cryotherapy to sensitize CaP to low temperature-induced, non-ice rupture-related cell death. VD3 (calcitriol) has been identified as a possible adjunct in the treatment of cancer because of its antiproliferative and antitumorigenic properties. This study aimed to identify the cellular responses and molecular pathways activated when VD3 (calcitriol) is combined with cryotherapy in a murine CaP model. Single freeze-thaw events above -15 °C had little effect on cancer cell viability; however, pretreatment with calcitriol in conjunction with cryo significantly increased cell death. The -15 °C calcitriol combination increased cell death to 55% following a single freeze compared with negligible cell loss by freezing or calcitriol alone. Repeated cryo combination yielded 90% cell death compared with 65% in dual freeze-only cycles. Western blot analysis following calcitriol cryosensitization regimes confirmed the activation of apoptosis. Specifically, proapoptotic Bid and procaspase-3 were found to decrease at 1 h following combination treatment, indicating cleavage to the active forms. A parallel in vivo study confirmed the increased cell death when combining cryotherapy with calcitriol pretreatment. The development of an adjunctive therapy combining calcitriol and cryotherapy represents a potentially highly effective, less toxic, minimally invasive treatment option. These results suggest a role for calcitriol and cryo as a combinatorial treatment for CaP, with the potential for clinical translation.

  1. Studies of a novel photosensitizer palladium-bacteriopheophorbide (Tookad) for the treatment of prostate cancer

    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.

    2003-06-01

    In this study, photodynamic therapy (PDT) mediated with a novel, second generation photosensitizer Tookad (palladium-bacteriopheophorbide, WST09, STEBA Biotech, France), is investigated as an alternative modality in the treatment of prostate cancer. In vivo normal canine prostate and spontaneous advanced prostate cancer are used as the animal model. 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. The effects of drug concentration, drug-light interval, and light fluence rate on the PDT efficacy were studied. The prostates and adjacent tissues (bladder and underlying colon) were harvested and subjected to histopathological examination. During the one-week to 3-month period post PDT treatment, the dogs recovered well with little or no urethral complications. Prostatic urethra and prostate adjacent tissues (bladder and underlying colon) were well preserved. Light irradiation delivered during drug infusion or within 15 min post drug infusion induced the similar extend of damages. PDT induced prostate lesions in both normal and cancerous prostate were characterized by marked hemorrhagic necrosis and atrophy. 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 cancerous prostatic tissue. In conclusion, the second generation photosensitizer Tookad mediated PDT may provide an effective alternative to treat prostate cancer.

  2. Solitary Fibrous Tumor of the Prostate Which Was Initially Misdiagnosed as Prostate Cancer

    PubMed Central

    Osamu, Soma; Murasawa, Hiromi; Yoneyama, Takahiro; Koie, Takuya; Ohyama, Chikara

    2017-01-01

    Solitary fibrous tumor (SFT) of the prostate is a very rare tumor. We report a case of 65-year-old man with SFT of the prostate which was initially misdiagnosed as prostate cancer. Finally, we performed total prostatectomy and the tumor was histologically diagnosed as SFT of the prostate. The patient's clinical course has progressed favorably with no obvious recurrence 18 months postoperatively.

  3. Exploiting a Molecular Gleason Grade for Prostate Cancer Therapy

    DTIC Science & Technology

    2010-03-01

    Exploiting a Molecular Gleason Grade for Prostate Cancer Therapy PRINCIPAL INVESTIGATOR: Peter S. Nelson, MD...Molecular Gleason Grade for Prostate Cancer Therapy 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-07-1-0149 5c. PROGRAM ELEMENT... levels of cognate serum proteins. #3 Write final report. (Note the original Aim 3 involving animal studies of altering prostate cancer grade

  4. Racial Disparities in Palliative Care for Prostate Cancer

    DTIC Science & Technology

    2013-10-01

    0802 TITLE: Racial Disparities in Palliative Care for Prostate Cancer PRINCIPAL INVESTIGATOR: Alfred I. Neugut, MD, PhD...Disparities in Palliative Care for Prostate Cancer 5b. GRANT NUMBER W81XWH-10-1-0802 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S... palliative treatments. 15. SUBJECT TERMS Prostate cancer, palliative care , ureteral obstruction, cord compression 16. SECURITY CLASSIFICATION OF

  5. Targeted Approach to Overcoming Treatment Resistance in Advanced Prostate Cancer

    DTIC Science & Technology

    2013-07-01

    therapy -­‐resistant   prostate   cancer  cells  and  in  combination   therapy  (SOW...treatment resistance in advanced prostate cancer PRINCIPAL INVESTIGATOR: Dr. Karin Scarpinato CONTRACTING ORGANIZATION: Georgia Southern...SUPPLEMENTARY NOTES 14. ABSTRACT The purpose of this project is to determine if rescinnamine is effective against prostate cancer and

  6. 76 FR 55551 - National Prostate Cancer Awareness Month, 2011

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-07

    ... Documents#0;#0; ] Proclamation 8706 of September 1, 2011 National Prostate Cancer Awareness Month, 2011 By the President of the United States of America A Proclamation Prostate cancer is the second leading... only by the men living with and fighting prostate cancer, but also by their families, friends,...

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

    DTIC Science & Technology

    2011-06-01

    endocannabinoid methanandamide- mediated cell proliferation and androgen receptor expression in EA006AA African American prostate cancer cells. 2...therapeutic intervention against prostate cancer Pilot Project #5: Feasibility of Endurance Exercise Training on Cardiovascular Risk Factors...endurance exercise training on exercise capacity following radical prostatectomy among with men with localized prostate cancer . 2. To assess the

  8. Exploiting the Immunological Effects of Standard Treatments in Prostate Cancer

    DTIC Science & Technology

    2009-03-01

    Exploiting the Immunological Effects of Standard Treatments in Prostate Cancer PRINCIPAL INVESTIGATOR: Brad H. Nelson, Ph.D...From - To) 1 MAR 2008 - 28 FEB 2009 4. TITLE AND SUBTITLE Exploiting the immunological effects of standard treatments in 5a. CONTRACT NUMBER...treatment of prostate cancer. 15. SUBJECT TERMS Tumor immunology , immunotherapy, prostate cancer, antibody, T cell, tumor antigen, hormone therapy

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

    DTIC Science & Technology

    2010-11-01

    producing hormones) 1 0 10 11 B8f. Watchful waiting (no treatment, wait and see if your prostate cancer grows) 1 0 10 11 B8g. Cryotherapy (process...your prostate cancer grows) 7 Cryotherapy (process to freeze and destroy prostate tissue) 8 Chemotherapy (use of anti-cancer drugs) 9 Any other

  10. Interleukin-17 promotes prostate cancer via MMP7-induced epithelial-to-mesenchymal transition

    PubMed Central

    Zhang, Q; Liu, S; Parajuli, KR; Zhang, W; Zhang, K; Mo, Z; Liu, J; Chen, Z; Yang, S; Wang, AR; Myers, L; You, Z

    2016-01-01

    Chronic inflammation has been associated with a variety of human cancers including prostate cancer. Interleukin-17 (IL-17) is a critical pro-inflammatory cytokine, which has been demonstrated to promote development of prostate cancer, colon cancer, skin cancer, breast cancer, lung cancer, and pancreas cancer. IL-17 promotes prostate adenocarcinoma with a concurrent increase of matrix metalloproteinase 7 (MMP7) expression in mouse prostate. Whether MMP7 mediates IL-17’s action and the underlying mechanisms remain unknown. We generated Mmp7 and Pten double knockout (Mmp7−/− in abbreviation) mouse model and demonstrated that MMP7 promotes prostate adenocarcinoma through induction of epithelial-to-mesenchymal transition (EMT) in Pten-null mice. MMP7 disrupted E-cadherin/β-catenin complex to up-regulate EMT transcription factors in mouse prostate tumors. IL-17 receptor C and Pten double knockout mice recapitulated the weak EMT characteristics observed in Mmp7−/− mice. IL-17 induced MMP7 and EMT in human prostate cancer LNCaP, C4-2B, and PC-3 cell lines, while siRNA knockdown of MMP7 inhibited IL-17-induced EMT. Compound III, a selective MMP7 inhibitor, decreased development of invasive prostate cancer in Pten single knockout mice. In human normal prostates and prostate tumors, IL-17 mRNA levels were positively correlated with MMP7 mRNA levels. These findings demonstrate that MMP7 mediates IL-17’s function in promoting prostate carcinogenesis through induction of EMT, indicating IL-17-MMP7-EMT axis as potential targets for developing new strategies in the prevention and treatment of prostate cancer. PMID:27375020

  11. The evolving biology and treatment of prostate cancer

    PubMed Central

    Taichman, Russel S.; Loberg, Robert D.; Mehra, Rohit; Pienta, Kenneth J.

    2007-01-01

    Since the effectiveness of androgen deprivation for treatment of advanced prostate cancer was first demonstrated, prevention strategies and medical therapies for prostate cancer have been based on understanding the biologic underpinnings of the disease. Prostate cancer treatment is one of the best examples of a systematic therapeutic approach to target not only the cancer cells themselves, but the microenvironment in which they are proliferating. As the population ages and prostate cancer prevalence increases, challenges remain in the diagnosis of clinically relevant prostate cancer as well as the management of the metastatic and androgen-independent metastatic disease states. PMID:17786228

  12. Proteomic identification of the lactate dehydrogenase A in a radioresistant prostate cancer xenograft mouse model for improving radiotherapy

    PubMed Central

    Hao, Jingli; Graham, Peter; Chang, Lei; Ni, Jie; Wasinger, Valerie; Beretov, Julia; Deng, Junli; Duan, Wei; Bucci, Joseph; Malouf, David; Gillatt, David; Li, Yong

    2016-01-01

    Radioresistance is a major challenge for prostate cancer (CaP) metastasis and recurrence after radiotherapy. This study aimed to identify potential protein markers and signaling pathways associated with radioresistance using a PC-3 radioresistant (RR) subcutaneous xenograft mouse model and verify the radiosensitization effect from a selected potential candidate. PC-3RR and PC-3 xenograft tumors were established and differential protein expression profiles from two groups of xenografts were analyzed using liquid chromatography tandem-mass spectrometry. One selected glycolysis marker, lactate dehydrogenase A (LDHA) was validated, and further investigated for its role in CaP radioresistance. We found that 378 proteins and 51 pathways were significantly differentially expressed between PC-3RR and PC-3 xenograft tumors, and that the glycolysis pathway is closely linked with CaP radioresistance. In addition, we also demonstrated that knock down of LDHA with siRNA or inhibition of LDHA activity with a LDHA specific inhibitor (FX-11), could sensitize PC-3RR cells to radiotherapy with reduced epithelial-mesenchymal transition, hypoxia, DNA repair ability and autophagy, as well as increased DNA double strand breaks and apoptosis. In summary, we identified a list of potential RR protein markers and important signaling pathways from a PC-3RR xenograft mouse model, and demonstrate that targeting LDHA combined with radiotherapy could increase radiosensitivity in RR CaP cells, suggesting that LDHA is an ideal therapeutic target to develop combination therapy for overcoming CaP radioresistance. PMID:27708237

  13. Molecular Mechanism of Nkx3.1 Deregulation and its Function in Murine Pten Prostate Cancer Model

    DTIC Science & Technology

    2006-09-01

    levels of either NKX3.1 (in red; red arrowheads) or AR (in green ; white arrowheads) expression. C: The relative expression levels of Nkx3.1, AR, and...the iQ SYBR Green Supermix (Bio-Rad). Quantitative PCR for each sample was run in triplicate. Results were analyzed by the relative quantification...25: 6464-6474, 2005. 20. Jennbacken, K., Gustavsson , H., Welen, K., Vallbo, C., and Damber, J. E. Prostate cancer progression into androgen

  14. Curcumin Based Drug Screening for Inhibitors of NF kappa B in a Cell Model of Prostate Cancer Progression

    DTIC Science & Technology

    2008-02-01

    West Society of Toxicology in Breckenridge, CO in September 2007: “Identification of Curcumin Analogs Toxic against Prostate Cancer Cells Through...quantitative structure-activity relationship ( QSAR ) and ligand-based virtual screening (LBVS) to explore the possibility of improving their efficacy...Student in my laboratory has presented part of this data at the 25th Annual Meeting of the Mountain West Society of Toxicology in Breckenridge, CO in

  15. Mechanisms of VEGF Availability in Prostate Cancer

    DTIC Science & Technology

    2005-01-01

    the information obtained from this proposal has now been used to further understand resistance to VEGF 7 therapy in cancer progression. We...prostate cancer biology. Thanks to this training, Dr. Monvoisin is currently faculty at the Institut de Physiologie et Biologie Cellulaires , Université de

  16. Regulation of the Prostate Cancer Tumor Microenvironment

    DTIC Science & Technology

    2015-04-01

    are interested in understanding the mechanisms for development of TILs and how they modulate prostate cancer. Our hypothesis is that the innate ...growth can be altered through modulating the composition of TILs through innate immunity. Body Pathogens or cancerous cells alike can produce danger... innate immunity, including Toll-like receptors (TLRs). Thirteen mammalian TLRs have been identified to date with ligands ranging from

  17. Role of Mitochondria in Prostate Cancer

    DTIC Science & Technology

    2006-12-01

    prostate epithelial cell line, PNT1A. This is consistent with the enzymatic activity and protein level of mGPDH. However, cytochrome c oxidase (COX...dehydrogenase; Reactive oxygen species; Cytochrome c oxidase ; Antioxidant enzymes; Liver tissues; Glycerophosphate shuttle; Prostate cancer...Although cytochrome c oxidase (COX) itself is not a source of ROS, inhibition of COX may facilitate ROS production from other complexes [11

  18. Beta Catenin in Prostate Cancer Apoptosis

    DTIC Science & Technology

    2014-04-01

    insensitive cell types to determine whether this apoptosis pathway is only specific to androgen sensitive cell types. In order to determine the role of β...obtained: Effect of TRAIL-TZD combination on the apoptosis potential and β-catenin expression of androgen sensitive and androgen insensitive prostate...and 22RV1) and androgen insensitive (DU145 and PC3) prostate cancer cells were treated with either DMSO or a combination of 100ng/ml TRAIL and

  19. Tyrosine Kinase Display of Prostate Cancer Cells

    DTIC Science & Technology

    2001-10-01

    transdifferentiation . The fact that some prostate cancer cell lines, such as LNCaP, can undergo NE differentiation suggests that at least a subset of NE cells is...Katz, C. A. Olsson, and R. Buttyan. 1997. Transdifferentiation of cultured human prostate cells to a neuroendocrine cell phenotype in a hormone...in the above-mentioned cases 3), and some of these cells can be induced to transdifferentiate are tyrosine kinases, which are known initiators of

  20. The Infectious Pathogenesis of Prostate Cancer

    DTIC Science & Technology

    2008-03-01

    Press, 2002:385. 11. Sutcliffe S, Giovannucci E, Alderete JF, et al. Plasma antibodies against Trichomonas vaginalis and subsequent risk of...consistently been identified. In this project, we are examining two specific infectious agents with respect to prostate cancer: T vaginalis , the...of the newly identified XMRV virus in prostate carcinogenesis and progression; 2-) To characterize the role of the infectious protozoa T. vaginalis

  1. Modifiable Prostate Cancer Risk Reduction and Early Detection Behaviors in Black Men

    ERIC Educational Resources Information Center

    Odedina, Folakemi T.; Scrivens, John J., Jr.; Larose-Pierre, Margareth; Emanuel, Frank; Adams, Angela Denise; Dagne, Getachew A.; Pressey, Shannon Alexis; Odedina, Oladapo

    2011-01-01

    Objective: To explore the personal factors related to modifiable prostate cancer risk-reduction and detection behaviors among black men. Methods: Three thousand four hundred thirty (3430) black men were surveyed and structural equation modeling employed to test study hypotheses. Results: Modifiable prostate cancer risk-reduction behavior was found…

  2. SU-E-QI-19: Evaluation of a Clinical 1.5T MRI for Prostate Cancer MRS Imaging Using a In Vivo Tumor Model

    SciTech Connect

    Chen, X; Chen, L; Hensley, H; Cvetkovic, D; Fan, J; Ma, C; Zhang, C

    2014-06-15

    Purpose: Magnetic resonance spectroscopic (MRS) imaging may provide important bio-markers to distinguish normal/cancerous prostate tissue. While MRS imaging requires a high uniform magnetic field, the ability of a clinical 1.5T MRI to achieve a comparable MRS signal is of interest for radiation treatment planning/assessment. This study is to evaluate the MRS imaging of a 1.5T clinical MRI for prostate cancers by comparing with a small animal 7T MRS scanner. Methods: A tumor model was developed by implanting LNCaP tumor cells in nude mice prostates. Tumor was monitored 3 weeks after implantation using MRI, and MRS imaging was performed on the tumor area when the tumor reached around 1cm in diameter. The 1.5T GE clinical MR scanner and the 7T Bruker small animal MR scanner were used for each mouse. MR spectrums acquired with these scanners were analyzed and compared. The signals of Choline and Citrate were considered. Results: The prostate tumor MR spectrum under the 1.5T clinical MRI showed a similar spectrum pattern to that acquired using the 7T animal MRI. The Choline signal (3.2ppm) is clear and there is no clear peak for Citrate (2.6ppm). However, the signal magnitude for Choline is not dominant compared to the background signal under 1.5T MRI. Typical cancerous prostate tissue MR spectrum with an increased Choline signal and a reduced Citrate signal was observed. In addition, signal variation is noticeable between repeated spectrum scans. The average of these scans showed a comparable and consistent spectrum to those under 7T MRI. Conclusion: The clinical 1.5T MRI is able to acquire a MR spectrum for prostate cancer comparable to those acquired using a dedicated 7T MRS scanner. However, to achieve a consistent and reliable spectrum, multiple repeated scans were necessary to get a statistical result and reduce the noise-induced artifact. This work was supported in part by the National Cancer Institute Grant R21 CA131979 and R01CA172638.

  3. Effects of exercise training on tumor hypoxia and vascular function in the rodent preclinical orthotopic prostate cancer model.

    PubMed

    McCullough, Danielle J; Nguyen, Linda M-D; Siemann, Dietmar W; Behnke, Bradley J

    2013-12-01

    Regular physical exercise is considered to be an integral component of cancer care strategies. However, the effect of exercise training on tumor microvascular oxygenation, hypoxia, and vascular function, all of which can affect the tumor microenvironment, remains unknown. Using an orthotopic preclinical model of prostate cancer, we tested the hypotheses that, after exercise training, in the tumor, there would be an enhanced microvascular Po2, increased number of patent vessels, and reduced hypoxia. We also investigated tumor resistance artery contractile properties. Dunning R-3327 AT-1 tumor cells (10(4)) were injected into the ventral prostate of 4-5-mo-old male Copenhagen or Nude rats, which were randomly assigned to tumor-bearing exercise trained (TB-Ex trained; n = 15; treadmill exercise for 5-7 wk) or sedentary groups (TB-Sedentary; n = 12). Phosphorescence quenching was used to measure tumor microvascular Po2, and Hoechst-33342 and EF-5 were used to measure patent vessels and tumor hypoxia, respectively. Tumor resistance artery function was assessed in vitro using the isolated microvessel technique. Compared with sedentary counterparts, tumor microvascular Po2 increased ∼100% after exercise training (TB-Sedentary, 6.0 ± 0.3 vs. TB-Ex Trained, 12.2 ± 1.0 mmHg, P < 0.05). Exercise training did not affect the number of patent vessels but did significantly reduce tumor hypoxia in the conscious, resting condition from 39 ± 12% of the tumor area in TB-Sedentary to 4 ± 1% in TB-Ex Trained. Exercise training did not affect vessel contractile function. These results demonstrate that after exercise training, there is a large increase in the driving force of O2 from the tumor microcirculation, which likely contributes to the considerable reduction in tumor hypoxia. These results suggest that exercise training can modulate the microenvironment of the tumor, such that a sustained reduction in tumor hypoxia occurs, which may lead to a less aggressive phenotype and

  4. Use of shear waves for diagnosis and ablation monitoring of prostate cancer: a feasibility study

    NASA Astrophysics Data System (ADS)

    Gomez, A.; Rus, G.; Saffari, N.

    2016-01-01

    Prostate cancer remains as a major healthcare issue. Limitations in current diagnosis and treatment monitoring techniques imply that there is still a need for improvements. The efficacy of prostate cancer diagnosis is still low, generating under and over diagnoses. High intensity focused ultrasound ablation is an emerging treatment modality, which enables the noninvasive ablation of pathogenic tissue. Clinical trials are being carried out to evaluate its longterm efficacy as a focal treatment for prostate cancer. Successful treatment of prostate cancer using non-invasive modalities is critically dependent on accurate diagnostic means and is greatly benefited by a real-time monitoring system. While magnetic resonance imaging remains the gold standard for prostate imaging, its wider implementation for prostate cancer diagnosis remains prohibitively expensive. Conventional ultrasound is currently limited to guiding biopsy. Elastography techniques are emerging as a promising real-time imaging method, as cancer nodules are usually stiffer than adjacent healthy prostatic tissue. In this paper, a new transurethral approach is proposed, using shear waves for diagnosis and ablation monitoring of prostate cancer. A finite-difference time domain model is developed for studying the feasibility of the method, and an inverse problem technique based on genetic algorithms is proposed for reconstructing the location, size and stiffness parameters of the tumour. Preliminary results indicate that the use of shear waves for diagnosis and monitoring ablation of prostate cancer is feasible.

  5. Androgen receptor profiling predicts prostate cancer outcome

    PubMed Central

    Stelloo, Suzan; Nevedomskaya, Ekaterina; van der Poel, Henk G; de Jong, Jeroen; van Leenders, Geert JLH; Jenster, Guido; Wessels, Lodewyk FA; Bergman, Andries M; Zwart, Wilbert

    2015-01-01

    Prostate cancer is the second most prevalent malignancy in men. Biomarkers for outcome prediction are urgently needed, so that high-risk patients could be monitored more closely postoperatively. To identify prognostic markers and to determine causal players in prostate cancer progression, we assessed changes in chromatin state during tumor development and progression. Based on this, we assessed genomewide androgen receptor/chromatin binding and identified a distinct androgen receptor/chromatin binding profile between primary prostate cancers and tumors with an acquired resistance to therapy. These differential androgen receptor/chromatin interactions dictated expression of a distinct gene signature with strong prognostic potential. Further refinement of the signature provided us with a concise list of nine genes that hallmark prostate cancer outcome in multiple independent validation series. In this report, we identified a novel gene expression signature for prostate cancer outcome through generation of multilevel genomic data on chromatin accessibility and transcriptional regulation and integration with publically available transcriptomic and clinical datastreams. By combining existing technologies, we propose a novel pipeline for biomarker discovery that is easily implementable in other fields of oncology. PMID:26412853

  6. A Novel Imaging Approach for Early Detection of Prostate Cancer Based on Endogenous Zinc Sensing

    PubMed Central

    Ghosh, Subrata K.; Kim, Pilhan; Zhang, Xiao-an; Yun, Seok-Hyun; Moore, Anna; Lippard, Stephen J.; Medarova, Zdravka

    2010-01-01

    The early detection of prostate cancer is a life-saving event in patients harboring potentially aggressive disease. With the development of malignancy there is a dramatic reduction in the zinc content of prostate tissue associated with the inability of cancer cells to accumulate the ion. In the current study, we utilized endogenous zinc as an imaging biomarker for prostate cancer detection and progression monitoring. We employed a novel fluorescent sensor for mobile zinc (ZPP1) to detect and monitor the development of prostate cancer in a transgenic mouse model of prostate adenocarcinoma, using in vivo optical imaging correlated with biological fluid-based methods. We demonstrated that the progression of prostate cancer could be monitored in vivo judging by decreasing zinc content in the prostates of tumor-bearing mice in an age-dependent manner. In a novel quantitative assay, we determine the concentration of mobile zinc in both prostate cell lysates and mouse prostate extracts through simple titration of the ZPP1 sensor. Our findings fulfill the promise of zinc-based prostate cancer diagnostics with the prospect for immediate clinical translation. PMID:20610630

  7. State-of-the-art imaging of prostate cancer.

    PubMed

    Marko, Jamie; Gould, C Frank; Bonavia, Grant H; Wolfman, Darcy J

    2016-03-01

    Prostate cancer is the most common cancer in men. Modern medical imaging is intimately involved in the diagnosis and management of prostate cancer. Ultrasound is primarily used to guide prostate biopsy to establish the diagnosis of prostate carcinoma. Prostate magnetic resonance imaging uses a multiparametric approach, including anatomic and functional imaging sequences. Multiparametric magnetic resonance imaging can be used for detection and localization of prostate cancer and to evaluate for disease recurrence. Computed tomography and scintigraphic imaging are primarily used to detect regional lymph node spread and distant metastases. Recent advancements in ultrasound, multiparametric magnetic resonance imaging, and scintigraphic imaging have the potential to change the way prostate cancer is diagnosed and managed. This article addresses the major imaging modalities involved in the evaluation of prostate cancer and updates the reader on the state of the art for each modality.

  8. Acne and risk of prostate cancer.

    PubMed

    Sutcliffe, Siobhan; Giovannucci, Edward; Isaacs, William B; Willett, Walter C; Platz, Elizabeth A

    2007-12-15

    In a recent study, prostatectomy specimens from which Propionibacterium acnes was cultured were more likely to have inflammation than culture-negative specimens or specimens positive for other bacteria, leading the authors to hypothesize that P. acnes-mediated inflammation may contribute to prostate carcinogenesis. To indirectly explore associations between P. acnes and prostate cancer, we investigated severe acne, as measured by tetracycline use for 4 or more years, in relation to incident prostate cancer in the Health Professionals Follow-up Study. On the 1992 follow-up questionnaire, participants were asked whether they had ever used "tetracycline for at least 2 months at a time (e.g., for acne or other reason)" and their duration of use. Prostate cancer diagnoses were ascertained on each subsequent biennial questionnaire and confirmed by medical record review. Between 1992 and 2002, 2,147 cases of prostate cancer were reported among 34,629 eligible participants. Men who used tetracycline for 4 or more years had a significantly higher risk of prostate cancer (16 cases, 1,569 person-years) than men who did not use tetracycline (2,071 cases, 304,822 person-years, multivariable-adjusted RR = 1.70, 95% CI: 1.03-2.80). Although intriguing, this finding should be viewed cautiously because of the small number of exposed cases, indirect assessment of severe acne, and complex etiology of acne, which is not limited to P. acnes infection. Therefore, additional biologic and epidemiologic studies are necessary to determine and elucidate the possible role of P. acnes infection in prostate carcinogenesis.

  9. Current clinical challenges in prostate cancer

    PubMed Central

    Silberstein, Jonathan L.; Pal, Sumanta Kumar; Lewis, Brian

    2013-01-01

    Prostate cancer is the most common malignancy and the second leading cause of cancer death in men in the United States. Close to $12 billion are spent annually on the treatment of prostate cancer in the US alone. Yet still there remain tremendous controversies and challenges that exist in all facets of the disease. This review and discussion will focus on issues and challenges for clinicians and patients diagnosed with the disease. Appropriate risk stratification for men with newly diagnosed prostate cancer is an appropriate first step for all patients. Once risk-stratified, for those with low-risk of death, it is increasingly recognized that overtreatment creates an unnecessary burden for many patients. This is particularly evident when put in the context of competing comorbidities in an elderly population. For those with advanced or high-risk localized disease, under-treatment remains too common. For those with a high-risk of recurrence or failure following primary treatment, adjuvant or salvage therapies are an option, but how and when to best deploy these treatments are controversial. Recently, tremendous progress has been made for those with advanced disease, in particular those with metastatic castrate-resistant prostate cancer (mCRPC). Within the last 4 years, five novel FDA approved agents, acting through distinct mechanisms have been FDA approved for mCRPC. With the introduction of these new agents a host of new challenges have arisen. Timing, sequencing and combinations of these novel agents are welcomed challenges when compared with the lack of available therapies just a few years ago. In this summary of current clinical challenges in prostate cancer we review critical recent studies that have created or shifted the current paradigms of treatment for prostate cancer. We will also highlight ongoing issues that continue to challenge our field. PMID:26816735

  10. [Pharmaco and diet based prostate cancer prevention].

    PubMed

    Eisinger, François; Cancel-Tassin, Géraldine; Azzouzi, Abdel Rahmene; Gravis, Gwenaelle; Rossi, Dominique; Cussenot, Olivier

    2013-05-01

    In 2010, in France, 8,790 men died from prostate cancer despite a low and decreasing mortality rate. The individual risk/benefit ratio of prostate cancer screening is the focus of controversy and currently not in favor of a systematic screening program. Therefore, only prevention could reduce incidence, side effects of treatment and related mortality. Interestingly, prostate cancer prevention is also a field of controversy mainly about 5-alpha-reductase inhibitors. However, it could be expected that pharmaco- or diet-based prevention will be a huge tool for cancer control, even more for prostate cancer burden. This review comprehensively analyses which molecules or compounds could be used in preventive trials. With regard to pharmaco-prevention, three different kinds of drugs could be identified. First drugs, which aim at mainly or even solely reduce prostate cancer risk such as 5-alpha-reductase inhibitors and selective estrogen receptor modulators. Drugs, which aim at wider preventive impact such as: nonsteroidal anti-inflammatory drugs or difluoromethylornithine. Lastly, drugs for which reducing prostate cancer incidence is merely a side effect such as statins, metformin or histones desacetylase inhibitors. With regard to diet-based prevention, two main approaches could be identified: aliments and nutriments, on one hand, and vitamin and minerals, on the other. Interestingly if compounds reach experimental plausibility, natural foods or even global diet seem to have a higher impact. Lastly, besides assessment of efficacy, effectiveness required the critical step of compliance, which might actually be the weakest link of the prevention chain.

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

    DTIC Science & Technology

    2014-10-01

    After five days in culture, slices were incubated in PBS with the ethidium homodimer-1 and calcein AM reagents that emit red fluorescence in dead...cells and green in viable cells, respectively. Visualization under a fluorescent microscope revealed primarily red (dead) cells in the benign slices...of the benign and malignant human prostate. Lab Invest 94, 208 (Feb, 2014). 3. S. A. Bigler, R. E. Deering , M. K. Brawer, Comparison of microscopic

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  14. Early detection of prostate cancer. Role of prostate-specific antigen.

    PubMed Central

    Prabhakaran, V. M.

    1996-01-01

    Pressure to request prostate-specific antigen (PSA) tests for early detection of prostate cancer in middle-aged and older men is increasing. However, current scientific data suggest that such testing does more harm than good. Most professional groups do not advise routine screening for prostate cancer. This paper reviews the current status of PSA testing. PMID:8653039

  15. Photoacoustic imaging of prostate cancer using cylinder diffuse radiation

    NASA Astrophysics Data System (ADS)

    Xie, Wenming; Li, Li; Li, Zhifang; Li, Hui

    2012-12-01

    Prostate cancer is one of diseases with high mortality in man. Many clinical imaging modalities are utilized for the detection, grading and staging of prostate cancer, such as ultrasound, CT, MRI, etc. But they lacked adequate sensitivity and specificity for finding cancer in transition or central zone of prostate. To overcome these problems, we propose a photoacoustic imaging modality based on cylinder diffuse radiation through urethra for prostate cancer detection. We measure the related parameters about this system like lateral resolution (~2mm) and axial resolution(~333μm). Finally, simulated sample was imaged by our system. The results demonstrate the feasibility for detecting prostate cancer by our system.

  16. LIGHT: A Novel Immunotherapy for Primary and Metastatic Prostate Cancer

    DTIC Science & Technology

    2014-09-01

    effects due to the loss of testosterone (including fatigue, decreased sexual desire, weight gain, loss of muscle mass and osteoporosis ) and the well...beyond the prostate, immunotherapy may be the only way to treat it [6, 7]. A majority of clinical trials for the immunotherapy of prostate cancer...Localized Prostate Cancer. J Sex Med, 2012. 5. Fitzpatrick, J.M., Management of localized prostate cancer in senior adults : the crucial role of comorbidity

  17. Role of Human Polyomavirus Bkv in Prostate Cancer

    DTIC Science & Technology

    2007-12-01

    been surgically removed due to prostate cancer diagnosis . A normal prostate is defined as prostate that has been removed either during autopsy or by...immunosuppressed transplant patients, in whom it is associated with haemorrhagic cystitis and polyomavirus nephropathy (5, 35, 58, 70). BKV transforms rodent cells...cystoprostatectomy specimens from bladder cancer patients with the diagnosis of muscle invasive high grade urothelial carcinoma, with no prostate cancer histology

  18. Increasing Sustained Participation in Free Mass Prostate Cancer Screening Clinics

    DTIC Science & Technology

    2005-05-01

    Prostate - Screening Clinic? If I had signs of prostate cancer I wanted to find out so - Newspaper that treatment decisions can be made early ...three study years. 15. SUBJECT TERMS Prostate Cancer, Screening, Early Detection, African Americans 16. SECURITY CLASSIFICATION OF: 17. LIMITATION 18...prostate cancer screening and early detection. Pastors who participated in a focus group in Year I continue to be contacted, and we continue to follow-up

  19. SOST Inhibits Prostate Cancer Invasion

    SciTech Connect

    Hudson, Bryan D.; Hum, Nicholas R.; Thomas, Cynthia B.; Kohlgruber, Ayano; Sebastian, Aimy; Collette, Nicole M.; Coleman, Matthew A.; Christiansen, Blaine A.; Loots, Gabriela G.

    2015-11-06

    Inhibitors of Wnt signaling have been shown to be involved in prostate cancer (PC) metastasis; however the role of Sclerostin (Sost) has not yet been explored. Here we show that elevated Wnt signaling derived from Sost deficient osteoblasts promotes PC invasion, while rhSOST has an inhibitory effect. In contrast, rhDKK1 promotes PC elongation and filopodia formation, morphological changes characteristic of an invasive phenotype. Furthermore, rhDKK1 was found to activate canonical Wnt signaling in PC3 cells, suggesting that SOST and DKK1 have opposing roles on Wnt signaling in this context. Gene expression analysis of PC3 cells co-cultured with OBs exhibiting varying amounts of Wnt signaling identified CRIM1 as one of the transcripts upregulated under highly invasive conditions. We found CRIM1 overexpression to also promote cell-invasion. These findings suggest that bone-derived Wnt signaling may enhance PC tropism by promoting CRIM1 expression and facilitating cancer cell invasion and adhesion to bone. We concluded that SOST and DKK1 have opposing effects on PC3 cell invasion and that bone-derived Wnt signaling positively contributes to the invasive phenotypes of PC3 cells by activating CRIM1 expression and facilitating PC-OB physical interaction. As such, we investigated the effects of high concentrations of SOST in vivo. In conclusion, we found that PC3-cells overexpressing SOST injected via the tail vein in NSG mice did not readily metastasize, and those injected intrafemorally had significantly reduced osteolysis, suggesting that targeting the molecular bone environment may influence bone metastatic prognosis in clinical settings.

  20. SOST Inhibits Prostate Cancer Invasion

    DOE PAGES

    Hudson, Bryan D.; Hum, Nicholas R.; Thomas, Cynthia B.; ...

    2015-11-06

    Inhibitors of Wnt signaling have been shown to be involved in prostate cancer (PC) metastasis; however the role of Sclerostin (Sost) has not yet been explored. Here we show that elevated Wnt signaling derived from Sost deficient osteoblasts promotes PC invasion, while rhSOST has an inhibitory effect. In contrast, rhDKK1 promotes PC elongation and filopodia formation, morphological changes characteristic of an invasive phenotype. Furthermore, rhDKK1 was found to activate canonical Wnt signaling in PC3 cells, suggesting that SOST and DKK1 have opposing roles on Wnt signaling in this context. Gene expression analysis of PC3 cells co-cultured with OBs exhibiting varyingmore » amounts of Wnt signaling identified CRIM1 as one of the transcripts upregulated under highly invasive conditions. We found CRIM1 overexpression to also promote cell-invasion. These findings suggest that bone-derived Wnt signaling may enhance PC tropism by promoting CRIM1 expression and facilitating cancer cell invasion and adhesion to bone. We concluded that SOST and DKK1 have opposing effects on PC3 cell invasion and that bone-derived Wnt signaling positively contributes to the invasive phenotypes of PC3 cells by activating CRIM1 expression and facilitating PC-OB physical interaction. As such, we investigated the effects of high concentrations of SOST in vivo. In conclusion, we found that PC3-cells overexpressing SOST injected via the tail vein in NSG mice did not readily metastasize, and those injected intrafemorally had significantly reduced osteolysis, suggesting that targeting the molecular bone environment may influence bone metastatic prognosis in clinical settings.« less

  1. Management of progressive metastatic prostate cancer.

    PubMed

    Waselenko, J K; Dawson, N A

    1997-10-01

    Metastatic prostate cancer is a growing health problem and is the second leading cause of cancer death in men. While the response of patients with metastatic prostate cancer to initial hormonal manipulation is excellent, the majority of patients eventually progress. As a result, a growing number of patients and their physicians need-to-find acceptable therapeutic alternatives. Fortunately, the number of therapies in the management armamentarium is growing and includes: alternative hormonal therapies, chemotherapy, radioisotopes, and investigational agents. The major focus of treatment has shifted to palliation and quality of life. The decline of prostate-specific antigen (PSA) has become another important end point as evidence supporting a correlation with prolonged survival mounts. Enrolling eligible patients in clinical trials is critical to the development of new treatment strategies for this difficult disease.

  2. A Promising Future for Prostate Cancer Diagnostics

    PubMed Central

    Assinder, Stephen J.; Bhoopalan, Vanitha

    2017-01-01

    It has been estimated that globally there is a death attributable to prostate cancer every four minutes. As life expectancy in all world regions increases, so too incidence of this disease of the ageing male will increase. For many men diagnosis occurs after presentation with symptoms of altered urinary dynamics. Unfortunately, these changes, whilst also associated with benign disease, are evident quite late in the aetiology of prostate cancer. Early detection provides for better management and prognosis. This Special Issue provides an up to date view of the advances made towards early diagnosis and prognosis. It provides reviews of advanced imaging techniques (e.g., multiparametric MRI and protocols), and of biomaterials and molecular biomarkers currently being explored (e.g., microRNAs, proteomics) and the technologies that are revolutionizing this field. It describes the multi-disciplinary approaches that are essential to inexpensive, deliverable and accurate platforms for prostate cancer diagnostics. PMID:28106714

  3. Clinical adenoviral gene therapy for prostate cancer.

    PubMed

    Schenk, Ellen; Essand, Magnus; Bangma, Chris H; Barber, Chris; Behr, Jean-Paul; Briggs, Simon; Carlisle, Robert; Cheng, Wing-Shing; Danielsson, Angelika; Dautzenberg, Iris J C; Dzojic, Helena; Erbacher, Patrick; Fisher, Kerry; Frazier, April; Georgopoulos, Lindsay J; Hoeben, Rob; Kochanek, Stefan; Koppers-Lalic, Daniela; Kraaij, Robert; Kreppel, Florian; Lindholm, Leif; Magnusson, Maria; Maitland, Norman; Neuberg, Patrick; Nilsson, Berith; Ogris, Manfred; Remy, Jean-Serge; Scaife, Michelle; Schooten, Erik; Seymour, Len; Totterman, Thomas; Uil, Taco G; Ulbrich, Karel; Veldhoven-Zweistra, Joke L M; de Vrij, Jeroen; van Weerden, Wytske; Wagner, Ernst; Willemsen, Ralph

    2010-07-01

    Prostate cancer is at present the most common malignancy in men in the Western world. When localized to the prostate, this disease can be treated by curative therapy such as surgery and radiotherapy. However, a substantial number of patients experience a recurrence, resulting in spreading of tumor cells to other parts of the body. In this advanced stage of the disease only palliative treatment is available. Therefore, there is a clear clinical need for new treatment modalities that can, on the one hand, enhance the cure rate of primary therapy for localized prostate cancer and, on the other hand, improve the treatment of metastasized disease. Gene therapy is now being explored in the clinic as a treatment option for the various stages of prostate cancer. Current clinical experiences are based predominantly on trials with adenoviral vectors. As the first of a trilogy of reviews on the state of the art and future prospects of gene therapy in prostate cancer, this review focuses on the clinical experiences and progress of adenovirus-mediated gene therapy for this disease.

  4. Effects of Brassicaceae Isothiocyanates on Prostate Cancer.

    PubMed

    Novío, Silvia; Cartea, María Elena; Soengas, Pilar; Freire-Garabal, Manuel; Núñez-Iglesias, María Jesús

    2016-05-12

    Despite the major progress made in the field of cancer biology, cancer is still one of the leading causes of mortality, and prostate cancer (PCa) is one of the most encountered malignancies among men. The effective management of this disease requires developing better anticancer agents with greater efficacy and fewer side effects. Nature is a large source for the development of chemotherapeutic agents, with more than 50% of current anticancer drugs being of natural origin. Isothiocyanates (ITCs) are degradation products from glucosinolates that are present in members of the family Brassicaceae. Although they are known for a variety of therapeutic effects, including antioxidant, immunostimulatory, anti-inflammatory, antiviral and antibacterial properties, nowadays, cell line and animal studies have additionally indicated the chemopreventive action without causing toxic side effects of ITCs. In this way, they can induce cell cycle arrest, activate apoptosis pathways, increase the sensitivity of resistant PCa to available chemodrugs, modulate epigenetic changes and downregulate activated signaling pathways, resulting in the inhibition of cell proliferation, progression and invasion-metastasis. The present review summarizes the chemopreventive role of ITCs with a particular emphasis on specific molecular targets and epigenetic alterations in in vitro and in vivo cancer animal models.

  5. The Genomic Evolution of Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    addition, multiple genetic alterations are associated with disease evolution in response to therapy. This project aims to characterize evolution of...of castrate resistant metastatic cancer from primary foci. 15. SUBJECT TERMS Cancer genetics , tumor evolution, tumor heterogeneity, prostate cancer... genetic alterations are found more often in advanced disease. It is not known if these arise after metastases occur or are found in a subclone of the

  6. [Prostate cancer external beam radiotherapy].

    PubMed

    de Crevoisier, R; Pommier, P; Latorzeff, I; Chapet, O; Chauvet, B; Hennequin, C

    2016-09-01

    The prostate external beam radiotherapy techniques are described, when irradiating the prostate or after prostatectomy, with and without pelvic lymph nodes. The following parts are presented: indications of radiotherapy, total dose and fractionation, planning CT image acquisition, volume of interest delineation (target volumes and organs at risk) and margins, Intensity modulated radiotherapy planning and corresponding dose-volume constraints, and finally Image guided radiotherapy.

  7. High Prevalence of Screen Detected Prostate Cancer in West Africans: Implications for Racial Disparity of Prostate Cancer

    PubMed Central

    Hsing, Ann W.; Yeboah, Edward; Biritwum, Richard; Tettey, Yao; De Marzo, Angelo M.; Adjei, Andrew; Netto, George J.; Yu, Kai; Li, Yan; Chokkalingam, Anand P.; Chu, Lisa W.; Chia, David; Partin, Alan; Thompson, Ian M.; Quraishi, Sabah M.; Niwa, Shelley; Tarone, Robert; Hoover, Robert N.

    2015-01-01

    Purpose To our knowledge the reasons for the high rates of prostate cancer in black American men are unknown. Genetic and lifestyle factors have been implicated. Better understanding of prostate cancer rates in West African men would help clarify why black American men have such high rates since the groups share genetic ancestry and yet have different lifestyles and screening practices. To estimate the prostate cancer burden in West African men we performed a population based screening study with biopsy confirmation in Ghana. Materials and Methods We randomly selected 1,037 healthy men 50 to 74 years old from Accra, Ghana for prostate cancer screening with prostate specific antigen testing and digital rectal examination. Men with a positive screen result (positive digital rectal examination or prostate specific antigen greater than 2.5 ng/ml) underwent transrectal ultrasound guided biopsies. Results Of the 1,037 men 154 (14.9%) had a positive digital rectal examination and 272 (26.2%) had prostate specific antigen greater than 2.5 ng/ml, including 166 with prostate specific antigen greater than 4.0 ng/ml. A total of 352 men (33.9%) had a positive screen by prostate specific antigen or digital rectal examination and 307 (87%) underwent biopsy. Of these men 73 were confirmed to have prostate cancer, yielding a 7.0% screen detected prostate cancer prevalence (65 patients), including 5.8% with prostate specific antigen greater than 4.0 ng/ml. Conclusions In this relatively unscreened population in Africa the screen detected prostate cancer prevalence is high, suggesting a possible role of genetics in prostate cancer etiology and the disparity in prostate cancer risk between black and white American men. Further studies are needed to confirm the high prostate cancer burden in African men and the role of genetics in prostate cancer etiology. PMID:24747091

  8. Hormone Therapy for Prostate Cancer

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  9. The influence of the local effect model parameters on the prediction of the tumor control probability for prostate cancer.

    PubMed

    Chanrion, M-A; Sauerwein, W; Jelen, U; Wittig, A; Engenhart-Cabillic, R; Beuve, M

    2014-06-21

    In carbon ion beams, biological effects vary along the ion track; hence, to quantify them, specific radiobiological models are needed. One of them, the local effect model (LEM), in particular version I (LEM I), is implemented in treatment planning systems (TPS) clinically used in European particle therapy centers. From the physical properties of the specific ion radiation, the LEM calculates the survival probabilities of the cell or tissue type under study, provided that some determinant input parameters are initially defined. Mathematical models can be used to predict, for instance, the tumor control probability (TCP), and then evaluate treatment outcomes. This work studies the influence of the LEM I input parameters on the TCP predictions in the specific case of prostate cancer. Several published input parameters and their combinations were tested. Their influence on the dose distributions calculated for a water phantom and for a patient geometry was evaluated using the TPS TRiP98. Changing input parameters induced clinically significant modifications of the mean dose (up to a factor of 3.5), spatial dose distribution, and TCP predictions (up to factor of 2.6 for D50). TCP predictions were found to be more sensitive to the parameter threshold dose (Dt) than to the biological parameters α and β. Additionally, an analytical expression was derived for correlating α, β and Dt, and this has emphasized the importance of [Formula: see text]. The improvement of radiobiological models for particle TPS will only be achieved when more patient outcome data with well-defined patient groups, fractionation schemes and well-defined end-points are available.

  10. Concepts of epigenetics in prostate cancer development

    PubMed Central

    Cooper, C S; Foster, C S

    2008-01-01

    Substantial evidence now supports the view that epigenetic changes have a role in the development of human prostate cancer. Analyses of the patterns of epigenetic alteration are providing important insights into the origin of this disease and have identified specific alterations that may serve as useful diagnostic and prognostic biomarkers. Examination of cancer methylation patterns supports a stem cell origin of prostate cancer. It is well established that methylation of GSTpi is a marker of prostate cancer, and global patterns of histone marking appear to be linked to cancer prognosis with levels of acetylated histones H3K9, H3K18, and H4K12, and of dimethylated H4R3 and H3K4, dividing low-grade prostate cancer (Gleason 6 or less) into two prognostically separate groups. Elevated levels of several components of the polycomb group protein complex, EZH2, BMI1, and RING1, can also act as biomarkers of poor clinical outcome. Many components of the epigenetic machinery, including histone deacetylase (whose expression level is linked to the TMPRSS2:ERG translocation) and the histone methylase EZH2, are potential therapeutic targets. The recent discovery of the role of small RNAs in governing the epigenetic status of individual genes offers exciting new possibilities in therapeutics and chemoprevention. PMID:19002169

  11. Nanoparticle therapeutics for prostate cancer treatment.

    PubMed

    Sanna, Vanna; Sechi, Mario

    2012-09-01

    The application of nanotechnology in medicine is offering many exciting possibilities in healthcare. Engineered nanoparticles have the potential to revolutionize the diagnosis and the therapy of several diseases, particularly by targeted delivery of anticancer drugs and imaging contrast agents. Prostate cancer, the second most common cancer in men, represents one of the major epidemiological problems, especially for patients in the advanced age. There is a substantial interest in developing therapeutic options for treatment of prostate cancer based on use of nanodevices, to overcome the lack of specificity of conventional chemotherapeutic agents as well as for the early detection of precancerous and malignant lesions. Herein, we highlight on the recent development of nanotechnology strategies adopted for the management of prostate cancer. In particular, the combination of targeted and controlled-release polymer nanotechnologies has recently resulted in the clinical development of BIND-014, a promising targeted Docetaxel-loaded nanoprototype, which can be validated for use in the prostate cancer therapy. However, several limitations facing nanoparticle delivery to solid tumours, such as heterogeneity of intratumoural barriers and vasculature, cytotoxicity and/or hypersensitivity reactions to currently available cancer nanomedicines, and the difficult in developing targeted nanoparticles with optimal biophysicochemical properties, should be still addressed for a successful tumour eradication.

  12. MAPS: A Quantitative Radiomics Approach for Prostate Cancer Detection.

    PubMed

    Cameron, Andrew; Khalvati, Farzad; Haider, Masoom A; Wong, Alexander

    2016-06-01

    This paper presents a quantitative radiomics feature model for performing prostate cancer detection using multiparametric MRI (mpMRI). It incorporates a novel tumor candidate identification algorithm to efficiently and thoroughly identify the regions of concern and constructs a comprehensive radiomics feature model to detect tumorous regions. In contrast to conventional automated classification schemes, this radiomics-based feature model aims to ground its decisions in a way that can be interpreted and understood by the diagnostician. This is done by grouping features into high-level feature categories which are already used by radiologists to diagnose prostate cancer: Morphology, Asymmetry, Physiology, and Size (MAPS), using biomarkers inspired by the PI-RADS guidelines for performing structured reporting on prostate MRI. Clinical mpMRI data were collected from 13 men with histology-confirmed prostate cancer and labeled by an experienced radiologist. These annotated data were used to train classifiers using the proposed radiomics-driven feature model in order to evaluate the classification performance. The preliminary experimental results indicated that the proposed model outperformed each of its constituent feature groups as well as a comparable conventional mpMRI feature model. A further validation of the proposed algorithm will be conducted using a larger dataset as future work.

  13. Chronic prostatic infection and inflammation by Propionibacterium acnes in a rat prostate infection model.

    PubMed

    Olsson, Jan; Drott, Johanna Bergh; Laurantzon, Lovisa; Laurantzon, Oscar; Bergh, Anders; Elgh, Fredrik

    2012-01-01

    Chronic inflammation in the prostate, seen as infiltration of inflammatory cells into the prostate gland in histological samples, affects approximately half the male population without indication of prostate disease, and is almost ubiquitous in patients diagnosed with benign prostate hyperplasia and cancer. Several studies have demonstrated the gram-positive bacterium Propionibacterium acnes to be frequently present in prostate tissue from men suffering from prostate disease. P. acnes has been shown to be associated with histological inflammation in human prostatectomy specimens, and also to induce strong inflammatory response in prostate-derived tissue culture models. The present paper describes a rat model for assessment of the pathogenic potential of P. acnes in prostate. Prostate glands of Sprague Dawley rats (n = 98) were exposed via an abdominal incision and live P. acnes or, in control rats, saline were injected into the ventral and dorso-lateral lobes. Rats were sacrificed 5 days, 3 weeks, 3 months and 6 months post infection, and prostate tissue was analyzed for bacterial content and histological inflammation. Rat sera were assessed for levels of CRP and anti-P. acnes IgG. Live P. acnes could be recovered from the dorso-lateral lobes up to 3 months post infection, while the ventral lobes were cleared from bacteria at that time. In samples up to 3 months post infection, the dorso-lateral lobes exhibited intense focal inflammation. CRP and IgG levels were elevated throughout the span of the experiment, and reached maximum levels 3 weeks and 3 months post infection, respectively. We show that P. acnes have the potential to cause chronic infection in previously healthy prostate, and that the infection has potential to cause chronic histological inflammation in the infected tissue. The high prevalence of P. acnes in human prostate tissue calls for resolution of pathogenic details. The present rat model suggests that complications such as chronic

  14. Chimeric Amino Acid Rearrangements as Immune Targets in Prostate Cancer

    DTIC Science & Technology

    2016-05-01

    cancer using a variety of approaches, including dendritic cell-based vaccines (e.g. Provegene), pox-based vaccines (e.g. PROSTVAC) as well as...Background: Cancer vaccines aim to elicit antigen-specific T cell responses against tumor antigens. Most prostate cancer vaccines to date target mis...therapeutic vaccination against fusion oncogenes in prostate cancer. IMMUNOGENICITY OF CHIMERIC AMINO ACID SEQUENCES IN PROSTATE CANCER Jennifer L

  15. Selective expression of myosin IC Isoform A in mouse and human cell lines and mouse prostate cancer tissues.

    PubMed

    Ihnatovych, Ivanna; Sielski, Neil L; Hofmann, Wilma A

    2014-01-01

    Myosin IC is a single headed member of the myosin superfamily. We recently identified a novel isoform and showed that the MYOIC gene in mammalian cells encodes three isoforms (isoforms A, B, and C). Furthermore, we demonstrated that myosin IC isoform A but not isoform B exhibits a tissue specific expression pattern. In this study, we extended our analysis of myosin IC isoform expression patterns by analyzing the protein and mRNA expression in various mammalian cell lines and in various prostate specimens and tumor tissues from the transgenic mouse prostate (TRAMP) model by immunoblotting, qRT-PCR, and by indirect immunohistochemical staining of paraffin embedded prostate specimen. Analysis of a panel of mammalian cell lines showed an increased mRNA and protein expression of specifically myosin IC isoform A in a panel of human and mouse prostate cancer cell lines but not in non-cancer prostate or other (non-prostate-) cancer cell lines. Furthermore, we demonstrate that myosin IC isoform A expression is significantly increased in TRAMP mouse prostate samples with prostatic intraepithelial neoplasia (PIN) lesions and in distant site metastases in lung and liver when compared to matched normal tissues. Our observations demonstrate specific changes in the expression of myosin IC isoform A that are concurrent with the occurrence of prostate cancer in the TRAMP mouse prostate cancer model that closely mimics clinical prostate cancer. These data suggest that elevated levels of myosin IC isoform A may be a potential marker for the detection of prostate cancer.

  16. A poxviral-based cancer vaccine targeting the transcription factor Twist inhibits primary tumor growth and metastases in a model of metastatic breast cancer and improves survival in a spontaneous prostate cancer model

    PubMed Central

    Kwilas, Anna R.; Ardiani, Andressa; Dirmeier, Ulrike; Wottawah, Cornelia

    2015-01-01

    Several transcription factors play a role in the alteration of gene expression that occurs during cancer metastasis. Twist expression has been shown to be associated with the hallmarks of the metastatic process, as well as poor prognosis and drug resistance in many tumor types. However, primarily due to their location within the cell and the lack of a hydrophobic groove required for drug attachment, transcription factors such as Twist are difficult to target with conventional therapies. An alternative therapeutic strategy is a vaccine comprised of a Modified vaccinia Ankara (MVA), incorporating the Twist transgene and a TRIad of COstimulatory Molecules (B7-1, ICAM-1, LFA-3; TRICOM). Here we characterize an MVA-TWIST/TRICOM vaccine that induced both CD4+ and CD8+ Twist-specific T-cell responses in vivo. In addition, administration of this vaccine reduced both the primary tumor growth and metastasis in the 4T1 model of metastatic breast cancer. In the TRAMP transgenic model of spontaneous prostate cancer, MVA-TWIST/TRICOM alone significantly improved survival, and when combined with the androgen receptor antagonist enzalutamide, the vaccine further improved survival. These studies thus provide a rationale for the use of active immunotherapy targeting transcription factors involved in the metastatic process and for the combination of cancer vaccines with androgen deprivation. PMID:26317648

  17. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of prostate carcinoma.

    PubMed

    McNeel, Douglas G; Bander, Neil H; Beer, Tomasz M; Drake, Charles G; Fong, Lawrence; Harrelson, Stacey; Kantoff, Philip W; Madan, Ravi A; Oh, William K; Peace, David J; Petrylak, Daniel P; Porterfield, Hank; Sartor, Oliver; Shore, Neal D; Slovin, Susan F; Stein, Mark N; Vieweg, Johannes; Gulley, James L

    2016-01-01

    Prostate cancer is the most commonly diagnosed malignancy and second leading cause of cancer death among men in the United States. In recent years, several new agents, including cancer immunotherapies, have been approved or are currently being investigated in late-stage clinical trials for the management of advanced prostate cancer. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel, including physicians, nurses, and patient advocates, to develop consensus recommendations for the clinical application of immunotherapy for prostate cancer patients. To do so, a systematic literature search was performed to identify high-impact papers from 2006 until 2014 and was further supplemented with literature provided by the panel. Results from the consensus panel voting and discussion as well as the literature review were used to rate supporting evidence and generate recommendations for the use of immunotherapy in prostate cancer patients. Sipuleucel-T, an autologous dendritic cell vaccine, is the first and currently only immunotherapeutic agent approved for the clinical management of metastatic castrate resistant prostate cancer (mCRPC). The consensus panel utilized this model to discuss immunotherapy in the treatment of prostate cancer, issues related to patient selection, monitoring of patients during and post treatment, and sequence/combination with other anti-cancer treatments. Potential immunotherapies emerging from late-stage clinical trials are also discussed. As immunotherapy evolves as a therapeutic option for the treatment of prostate cancer, these recommendations will be updated accordingly.

  18. Dietary phenethyl isothiocyanate inhibition of androgen-responsive LNCaP prostate cancer cell tumor growth correlates with decreased angiogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phenethyl isothiocyanate (PEITC), found in certain cruciferous vegetables, has antitumor activity in several cancer models, including prostate cancer. In our xenograft model, dietary administration of PEITC (100-150 mg/kg/d) inhibited androgen-responsive LNCaP human prostate cancer cell tumor growth...

  19. Prostate Specific or Enriched Genes as Composite Biomarkers for Prostate Cancer

    DTIC Science & Technology

    2010-02-01

    research: To evaluate prostate specific genes such as WDR19, NDRG1 , TAGLN2 as diagnosis and prognosis markers for prostate cancers. Major findings: (1) We...have determined that WDR19, NDRG1 are not as good a marker as PSA for prostate cancer stratification. (2) We developed a mouse antibody for a...optimize sandwich ELISA assays for WDR19, NDRG1 , or other novel prostate-specific biomarker candidates. During the past two years, we have evaluated the

  20. A Hybrid Systems Approach to Hormonal Therapy of Prostate Cancer and its Nonlinear Dynamics

    SciTech Connect

    Aihara, Kazuyuki; Tanaka, Gouhei; Suzuki, Taiji; Hirata, Yoshito

    2007-07-13

    This talk is to review our recent work on mathematical modeling of prostate cancer and its application to hormonal therapy of intermittent androgen suppression. First, we model the tumor growth of prostate cancer composed of a mixed dynamical assembly of androgen-dependent and androgen-independent cancer cells. Then, we introduce the intermittent androgen suppression to the model as feedback control with monitoring the serum prostate-specific antigen, where the controlled model is described as a hybrid system with continuous and discrete variables. Next, we analyze nonlinear dynamics and bifurcations of the hybrid system. Finally, we discuss a possibility to improve the hormonal therapy.