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Sample records for prostate cancer effect

  1. 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 ...

  2. 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 ...

  3. Prostate Cancer

    MedlinePlus

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

  4. 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.

  5. Genetic variation: effect on prostate cancer

    PubMed Central

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

    2014-01-01

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

  6. Quality of Life and Cost Effectiveness of Prostate Cancer Treatment

    DTIC Science & Technology

    2005-03-01

    AD Award Number: W81XWH-04-1-0257 TITLE: Quality of Life and Cost Effectiveness of Prostate Cancer Treatment PRINCIPAL INVESTIGATOR: Ravishankar...patients across two ethnic groups, (2) analyze and compare short and long term cost-effectiveness of prostate cancer treatment across ethnic groups; and...cost-effectiveness of prostate cancer treatment across ethnic groups; and (3) analyze and compare resource utilization patterns, treatment modalities

  7. Prostate Cancer

    MedlinePlus

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

  8. 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.

  9. Prostate Cancer Screening

    MedlinePlus

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

  10. 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.

  11. Physical activity and its mechanistic effects on prostate cancer.

    PubMed

    Wekesa, A; Harrison, M; Watson, R W

    2015-09-01

    Beneficial effects of physical activity have been illustrated in numerous aspects of health. With the increasing incidence of prostate cancer and changes in physical activity of men, understanding the link between the two has important implications for changing this cancer burden. Both positive and negative associations between physical activity and prostate cancer have been previously demonstrated in observational epidemiological studies. Elucidating the biological mechanisms would lead to a better understanding of how physical activity influences the progression of prostate cancer. This review was undertaken to: (1) identify evidence in literature that demonstrates the effects of physical activity on skeletal muscle secretomes, (2) indicate the plausible signaling pathways these proteins might activate, and (3) identify evidence in literature that demonstrates the roles of the signaling pathways in prostate cancer progression and regression. We also discuss proposed biological mechanisms and signaling pathways by which physical activity may prevent the development and progression of prostate cancer. We discuss proteins involved in the normal and aberrant growth and development of the prostate gland that may be affected by physical activity. We further identify future directions for research, including a better understanding of the biological mechanisms, the need to standardize physical activity and identify mechanistic end points of physical activity that can then be correlated with outcomes.

  12. 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 ...

  13. [Prostate cancer].

    PubMed

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

    2016-02-05

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

  14. [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.

  15. [The effect of castration on bone in prostate cancer patients].

    PubMed

    Vaarala, Markku; Kähkönen, Esa; Viitanen, Jouko; Taari, Kimmo; Tammela, Teuvo

    2011-01-01

    Surgical or chemical castration is widely used for the treatment of advanced prostate cancer. Common side effects of castration are e.g. sweating, increased body fat, decreased muscle mass, impotency and anemia. Castration increases the risk of osteoporosis and fractures in prostate cancer patients via hormonal effects to the bone. Castrated men should be recommended to increase physical activity. Calcium and vitamin-D supplementation is recommended. The European Association of Urology guidelines for prostate cancer recommend bone mineral density measurements before long-lasting castration therapy. Medical therapy should be considered for patients after low-energy fractures, after the diagnosis of osteoporosis based on bone mineral density measurements and for fracture high-risk patients based on clinical decision.

  16. 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

  17. 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/ ...

  18. Risks of Prostate Cancer Screening

    MedlinePlus

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

  19. [Treatment effect of breast cancer and prostate cancer on bone].

    PubMed

    Varsavsky, Mariela; Guadalix Iglesias, Sonsoles

    2013-02-16

    Aromatase inhibitors are used in the treatment of breast cancer and androgen deprivation therapy is used in prostate cancer. Both of them induce bone loss and increase fracture incidence. Early detection is important for patients with increased risk of osteoporotic fractures. In this article we review the available treatments and their indication to prevent the onset of osteoporosis and osteoporotic fractures in this patient group. Copyright © 2012 Elsevier España, S.L. All rights reserved.

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

    PubMed Central

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

    2010-01-01

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

  1. 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 ...

  2. Proapoptotic effect of endocannabinoids in prostate cancer cells

    PubMed Central

    ORELLANA-SERRADELL, O.; POBLETE, C.E.; SANCHEZ, C.; CASTELLÓN, E.A.; GALLEGOS, I.; HUIDOBRO, C.; LLANOS, M.N.; CONTRERAS, H.R.

    2015-01-01

    In the early stages, prostate cancer is androgen- dependent; therefore, medical castration has shown significant results during the initial stages of this pathology. Despite this early effect, advanced prostate cancer is resilient to such treatment. Recent evidence shows that derivatives of Cannabis sativa and its analogs may exert a protective effect against different types of oncologic pathologies. The purpose of the present study was to detect the presence of cannabinoid receptors (CB1 and CB2) on cancer cells with a prostatic origin and to evaluate the effect of the in vitro use of synthetic analogs. In order to do this, we used a commercial cell line and primary cultures derived from prostate cancer and benign prostatic hyperplasia. The presence of the CB1 and CB2 receptors was determined by immunohistochemistry where we showed a higher expression of these receptors in later stages of the disease (samples with a high Gleason score). Later, treatments were conducted using anandamide, 2-arachidonoyl glycerol and a synthetic analog of anandamide, methanandamide. Using the MTT assay, we proved that the treatments produced a cell growth inhibitory effect on all the different prostate cancer cultures. This effect was demonstrated to be dose-dependent. The use of a specific CB1 receptor blocker (SR141716) confirmed that this effect was produced primarily from the activation of the CB1 receptor. In order to understand the MTT assay results, we determined cell cycle distribution by flow cytometry, which showed no variation at the different cell cycle stages in all the cultures after treatment. Treatment with endocannabinoids resulted in an increase in the percentage of apoptotic cells as determined by Annexin V assays and caused an increase in the levels of activated caspase-3 and a reduction in the levels of Bcl-2 confirming that the reduction in cell viability noted in the MTT assay was caused by the activation of the apoptotic pathway. Finally, we observed that

  3. Tanshinones as Effective Therapeutic Agents for Prostate Cancer

    DTIC Science & Technology

    2011-06-01

    disappoint- ing.25 In the prostate cancer prevention trial (PCPT trial), finasteride , a 5a-reductase inhibitor, reduced the risk of pros- tate cancer by...associated with finasteride , the results may need further confirmation from another clinical trial, the Reduction by Dutasteride of prostate cancer...LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, et al. The influence of finasteride on the development of prostate cancer. N Engl

  4. 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.

  5. Inhibitory effects of megakaryocytic cells in prostate cancer skeletal metastasis.

    PubMed

    Li, Xin; Koh, Amy J; Wang, Zhengyan; Soki, Fabiana N; Park, Serk In; Pienta, Kenneth J; McCauley, Laurie K

    2011-01-01

    Prostate cancer cells commonly spread through the circulation, but few successfully generate metastatic foci in bone. Osteoclastic cellular activity has been proposed as an initiating event for skeletal metastasis. Megakaryocytes (MKs) inhibit osteoclastogenesis, which could have an impact on tumor establishment in bone. Given the location of mature MKs at vascular sinusoids, they may be the first cells to physically encounter cancer cells as they enter the bone marrow. Identification of the interaction between MKs and prostate cancer cells was the focus of this study. K562 (human MK precursors) and primary MKs derived from mouse bone marrow hematopoietic precursor cells potently suppressed prostate carcinoma PC-3 cells in coculture. The inhibitory effects were specific to prostate carcinoma cells and were enhanced by direct cell-cell contact. Flow cytometry for propidium iodide (PI) and annexin V supported a proapoptotic role for K562 cells in limiting PC-3 cells. Gene expression analysis revealed reduced mRNA levels for cyclin D1, whereas mRNA levels of apoptosis-associated specklike protein containing a CARD (ASC) and death-associated protein kinase 1 (DAPK1) were increased in PC-3 cells after coculture with K562 cells. Recombinant thrombopoietin (TPO) was used to expand MKs in the marrow and resulted in decreased skeletal lesion development after intracardiac tumor inoculation. These novel findings suggest a potent inhibitory role of MKs in prostate carcinoma cell growth in vitro and in vivo. This new finding, of an interaction of metastatic tumors and hematopoietic cells during tumor colonization in bone, ultimately will lead to improved therapeutic interventions for prostate cancer patients.

  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. Radiation Effects on the Immune Response to Prostate Cancer

    DTIC Science & Technology

    2009-02-01

    candidate to be used in conjunction with cancer immunotherapy . APPENDIX – see publication attached. ...to Prostate Cancer PRINCIPAL INVESTIGATOR: William H. McBride CONTRACTING ORGANIZATION: University of California...on the Immune Response to Prostate Cancer 5b. GRANT NUMBER W81XWH-07-1-0135 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER

  8. 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 ...

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

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0503 TITLE: “Effect of Diabetes and Obesity on Disparities in Prostate Cancer Outcomes PRINCIPAL INVESTIGATOR: Bettina F...RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2015 2. REPORT TYPE Annual 3. DATES COVERED 20154. TITLE AND SUBTITLE Effect of Diabetes ... diabetes (at prostate cancer diagnosis and during follow- up) and prostate cancer recurrence and mortality; as well as the combined effect of obesity

  10. 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

  11. Molecular effects of soy phytoalexin glyceollins in human prostate cancer cells LNCaP

    USDA-ARS?s Scientific Manuscript database

    Glyceollins are soy–derived phytoalexins that have been proposed to be candidate cancer preventive compounds. The effect of the glyceollins on prostate cancer is unknown. The present study examined the molecular effects of soy phytoalexins, glyceollins, on the human prostate cancer cell line LNCaP t...

  12. The effect of lycopene on the PI3K/Akt signalling pathway in prostate cancer.

    PubMed

    Chen, Jiezhong; O'Donoghue, Adam; Deng, Yi-Fu; Zhang, Bing; Kent, Fanning; O'Hare, Tim

    2014-01-01

    Prostate cancer is common in men with very high mortality which is one of leading causes of cancer-related deaths in men. The main treatment approaches for metastasized prostate cancer are androgen deprivation and chemotherapeutic agents. Although there are initial responses to castration, the resistance to the treatment will eventually occur, leading to castration-resistant prostate cancer. The common chemotherapeutic agents for the treatment of prostate cancer are docetaxel and taxane but outcomes of using these drugs have not been satisfactory. Therefore, it is necessary to find better treatment approaches for prostate cancer and to search for compounds that are effective in prostate cancer prevention. Lycopene extracted from tomato and other fruits or plants such as Gac, watermelon, pink grapefruit, pink guava, red carrot and papaya has been shown to be effective on prostate cancer prevention and treatment. The advantage of the application of lycopene for its anti-prostate cancer activity is that lycopene can reach much higher concentration in prostate tissue than other tissues. In this review, the effect of lycopene on PI3K/Akt pathway is summarised, which could be one of major mechanisms for anti-cancer activity of lycopene.

  13. Obesity and Prostate Cancer.

    PubMed

    Cao, Yin; Giovannucci, Edward

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

  14. Understanding the causes of depression among prostate cancer patients: development of the Effects of Prostate Cancer on Lifestyle Questionnaire.

    PubMed

    Sharpley, Christopher F; Bitsika, Vicki; Christie, David R H

    2009-02-01

    Depression among prostate cancer patients remains a major source of distress for them and their families, has been linked with suicide, and has been shown to contribute to poorer longterm treatment outcomes. Most psychological assessment strategies focus upon the presence of depressive symptomatology without identifying the specific causal antecedents that lead to depression among this patient group, although this underlies effective individually-oriented treatment planning and delivery. 150 prostate cancer patients completed self reports on anxiety, depression and lifestyle changes that they had experienced as a result of receiving a diagnosis of, and treatment for their cancer. The principal instrument being investigated was a measure of 50 lifestyle changes that had been developed from previous interviews with prostate cancer patients. Data indicated significant relationships between depression scores and the frequency of unpleasant lifestyle changes and the ratings that participants gave to these changes, supporting a model of depression as an adaptive withdrawal from noxious stimuli and environments. Psychometric data provided a method of deleting several items so that a clinical analysis and a research scale of 36 items was developed for use with prostate cancer patients. Implications for treatment are discussed in terms of accurate identification of antecedents that lead to a further understanding of depression as an 'adaptive' response of active withdrawal from noxious environments. (c) 2008 John Wiley & Sons, Ltd.

  15. What is Prostate Cancer?

    MedlinePlus

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

  16. Prostate Cancer for the Internist.

    PubMed

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

    2015-10-01

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

  17. Proteomic Analysis of Prostate Cancer Field Effect

    DTIC Science & Technology

    2011-02-01

    fragile X mental retardation protein interacting protein 1 [Homo sapiens] alpha-2-macroglobulin precursor [Homo sapiens] filamin A, alpha isoform 1...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT We have undertaken a novel proteomic approach to identify proteins ...in normal cells, to discover cancer altered protein that could be more abundant in serum or urine since they would come from both benign and cancer

  18. Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

    SciTech Connect

    Alizadeh, Moein; Sylvestre, Marie-Pierre; Zilli, Thomas; Van Nguyen, Thu; Guay, Jean-Pierre; Bahary, Jean-Paul; Taussky, Daniel

    2012-07-15

    Purpose: Statins and anticoagulants (ACs) have both been associated with a less-aggressive prostate cancer (PCa) and a better outcome after treatment of localized PCa. The results of these studies might have been confounded because patients might often take both medications. We examined their respective influence on PCa aggressiveness at initial diagnosis. Materials and Methods: We analyzed 381 patients treated with either external beam radiotherapy or brachytherapy for low-risk (n = 152), intermediate-risk (n = 142), or high-risk (n = 87) localized PCa. Univariate and multivariate logistic regression analyses were used to investigate an association between these drug classes and prostate cancer aggressiveness. We tested whether the concomitant use of statins and ACs had a different effect than that of either AC or statin use alone. Results: Of the 381 patients, 172 (45.1%) were taking statins and 141 (37.0%) ACs; 105 patients (27.6%) used both. On univariate analysis, the statin and AC users were associated with the prostate-specific antigen (PSA) level (p = .017) and National Comprehensive Cancer Network risk group (p = .0022). On multivariate analysis, statin use was associated with a PSA level <10 ng/mL (odds ratio, 2.9; 95% confidence interval, 1.3-6.8; p = .012) and a PSA level >20 ng/mL (odds ratio, 0.29; 95% confidence interval, 0.08-0.83; p = .03). The use of ACs was associated with a PSA level >20 ng/mL (odds ratio, 0.13; 95% confidence interval, 0.02-0.59, p = .02). Conclusion: Both AC and statins have an effect on PCa aggressiveness, with statins having a more stringent relationship with the PSA level, highlighting the importance of considering statin use in studies of PCa aggressiveness.

  19. Chemopreventive effect of PSP through targeting of prostate cancer stem cell-like population.

    PubMed

    Luk, Sze-Ue; Lee, Terence Kin-Wah; Liu, Ji; Lee, Davy Tak-Wing; Chiu, Yung-Tuen; Ma, Stephanie; Ng, Irene Oi-Lin; Wong, Yong-Chuan; Chan, Franky Leung; Ling, Ming-Tat

    2011-01-01

    Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer.

  20. Screening for Prostate Cancer

    MedlinePlus

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

  1. Prostate Cancer FAQs

    MedlinePlus

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

  2. Prostate Cancer Symptoms

    MedlinePlus

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

  3. 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 ...

  4. 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

  5. Effects of cisplatin on the LSD1-mediated invasion and metastasis of prostate cancer cells

    PubMed Central

    Chen, Zhi-Yuan; Chen, Hui; Qiu, Tao; Weng, Xiao-Dong; Guo, Jia; Wang, Lei; Liu, Xiu-Heng

    2016-01-01

    Prostate cancer poses a major public health problem in men. Metastatic prostate cancer is incurable, and ultimately threatens the life of patients. Lysine-specific demethylase 1 (LSD1) is an androgen receptor-interacting protein that exerts a key role in regulating gene expression and is involved in numerous biological processes associated with prostate cancer. Cisplatin, also known as cis-diamminedichloroplatinum or DDP, is a standard chemotherapeutic agent used to treat prostate cancer; however, it has the disadvantage of various serious side effects. The present study aimed to investigate the effects of LSD1 knockdown, and the interplay between LSD1 and DDP, on prostate cancer cell proliferation, apoptosis and invasion, and, therefore, the potential of LSD1 as a target for prostate cancer therapy. Flow cytometric analysis, Cell Counting kit 8 assay, Transwell assay and western blotting results revealed that LSD1 knockdown, in combination with DDP treatment, exerted antiproliferative, proapoptotic and anti–invasive effects on PC3 prostate cancer cells. In addition, knockdown of LSD1 acted synergistically with DDP, thereby enhancing the induction of apoptosis, and the inhibition of proliferation and invasion in prostate cancer cells. These results indicated that LSD1 may serve as a potential therapeutic target, and may enhance the sensitivity of PC3 cells to DDP. PMID:27484796

  6. [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.

  7. Comparative effectiveness of external beam radiation approaches for prostate cancer

    PubMed Central

    Jacobs, Bruce L.; Zhang, Yun; Skolarus, Ted A.; Wei, John T.; Montie, James E.; Miller, David C.; Hollenbeck, Brent K.

    2014-01-01

    Background Intensity-modulated radiotherapy (IMRT) is increasingly used for treating localized prostate cancer. While allowing for the delivery of higher doses of radiation to the prostate, its effectiveness compared to the prior standard, 3-dimensional conformal therapy (3D-CRT), is uncertain. Objective To examine the comparative effectiveness of IMRT relative to 3D-CRT. Design, setting, and participants We performed a population-based cohort study using Surveillance, Epidemiology, and End Results (SEER)-Medicare data to identify men diagnosed with prostate cancer between 2001 and 2007 who underwent either 3D-CRT (n=6,976) or IMRT (n=11,039). Measurements We assessed our main outcomes (i.e., the adjusted use of salvage therapy with androgen deprivation therapy (ADT) and risk of a complication requiring an intervention) using Cox proportional-hazards models. Results and limitations The percentage of men receiving IMRT increased from 9% in 2001 to 93% in 2007. Compared to those treated with 3D-CRT, low-risk patients treated with IMRT had similar likelihoods of using salvage therapy with ADT and similar risks of having a complication requiring an intervention (all p>0.05). Conversely, a subset of higher-risk patients treated with IMRT who did not receive concurrent ADT were less likely to use salvage therapy (p=0.02), while maintaining similar complication rates. Since our cohort includes Medicare beneficiaries, our findings may not be generalizable to younger patients. Conclusions For a subset of higher-risk patients, IMRT appears to show a benefit in terms of reduced salvage therapy without an increase in complications. For other patients, the risks of salvage therapy and complications are comparable between the two modalities. PMID:22790288

  8. Hypofractionation for prostate cancer.

    PubMed

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

    2009-01-01

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

  9. [Overdiagnosis in prostate cancer].

    PubMed

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

    2014-06-01

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

  10. Orchidectomy versus oestrogen for prostatic cancer: cardiovascular effects.

    PubMed Central

    Henriksson, P; Edhag, O

    1986-01-01

    One hundred consecutive patients aged up to 75 with newly diagnosed cancer of the prostate suitable for hormonal treatment were included in a controlled study of the cardiovascular effects of oestrogen versus orchidectomy. In all cases pre-existing cardiovascular morbidity was excluded. Of the 100 patients, 91 were strictly randomised to receive either oestrogen (n = 47) or orchidectomy (n = 44) and 9 (6 given oestrogen, 3 orchidectomy) either chose their own treatment (five cases) or had it selected for them by the urologist (four). Oestrogen was given in the lowest recommended dosage in Sweden--namely, as 160 mg polyestradiol phosphate intramuscularly every month for the first three months, then 80 mg monthly, plus ethinyloestradiol 1 mg by mouth daily for the first two weeks, then 150 micrograms daily. At entry to the study the two treatment groups showed no difference in demographic characteristics or conventional risk factors for cardiovascular disease. During the first year, however, 13 (25%) of the patients given oestrogen suffered major cardiovascular events as compared with none of the patients after orchidectomy. Patients in the oestrogen treatment group who did not have minor signs of atherosclerosis at entry to the study suffered a similar incidence of cardiovascular complications to those who did have these signs at entry. The substantially increased risk of cardiovascular complications in patients given oestrogen for prostatic cancer warrants careful consideration when choosing treatment for this disorder. PMID:3091138

  11. [Diet and prostate cancer].

    PubMed

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

    2003-06-01

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

  12. Proteomic Analysis of Prostate Cancer Field Effect

    DTIC Science & Technology

    2008-12-01

    frozen sections, stains them with hematoxylin and eosin , and she and Dr. Wilson review them with Dr. Stephen Ewing, Chief of Pathology Service at...specimen available. The thickness of frozen sections and the effect of the Arcturus stain were examined with respect to quality of LCM isolated 4 4...when the LCM capture caps were lifted from the slide. Use of frozen sections at 7 micron thickness minimized this, but did not totally eliminate it

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

    PubMed

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

    2007-10-01

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

  14. Effect of Metformin on Cancer Risk and Treatment Outcome of Prostate Cancer: A Meta-Analysis of Epidemiological Observational Studies

    PubMed Central

    Yu, Hongliang; Yin, Li; Jiang, Xuesong; Sun, Xiujin; Wu, Jing; Tian, Hao; Gao, Xianshu; He, Xia

    2014-01-01

    Background Laboratory studies have shown the anti-tumor effect of metformin on prostate cancer. However, recent epidemiological studies have yielded inconclusive results. Methods We searched PubMed database from the inception to May 30 2014 for studies which assessed the effect of metformin use on cancer risk of prostate cancer, biochemical recurrence (BCR) and all-cause mortality of patients with prostate cancer. The pooled results and 95% confidence intervals (CIs) were estimated by random-effect model. Results Twenty-one studies were eligible according to the inclusion criteria. Based on the pooled results of available observational studies, metformin use was significantly associated with a decreased cancer risk (14 datasets, 963991 male subjects, odds ratio: 0.91, 95% CI: 0.85–0.97) and BCR (6 datasets, 2953 patients, hazard ratio: 0.81, 95% CI: 0.68–0.98) of prostate cancer. However, the association of metformin use with all-cause mortality of patients with prostate cancer was not significant (5 datasets, 9241 patients, hazard ratio: 0.86, 95% CI: 0.64–1.14). Conclusion Results suggest that metformin use appears to be associated with a significant reduction in the cancer risk and BCR of prostate cancer, but not in all-cause mortality of patients with prostate cancer. PMID:25545701

  15. Selenoproteins and Prostate Cancer

    DTIC Science & Technology

    2005-11-01

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

  16. 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.…

  17. Counseling the Client with Prostate Cancer.

    ERIC Educational Resources Information Center

    Curtis, Russell C.; Juhnke, Gerald A.

    2003-01-01

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

  18. 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.

  19. Effect of Finasteride on Serum Androstenedione and Risk of Prostate Cancer within the Prostate Cancer Prevention Trial: Differential Effect on High and Low Grade Disease

    PubMed Central

    Hoque, Ashraful; Yao, Song; Till, Cathee; Kristal, Alan R.; Goodman, Phyllis J.; Hsing, Ann W.; Tangen, Catherine M.; Platz, Elizabeth A.; Stanczyk, Frank Z.; Reichardt, Juergen K.V.; vanBokhoven, Adrie; Neuhouser, Marian L.; Santella, Regina M.; Figg, William D.; Price, Douglas K.; Parnes, Howard L.; Lippman, Scott M.; Ambrosone, Christine B.; Thompson, Ian M.

    2014-01-01

    Objectives To evaluate the effect of finasteride on serum Androst-4-ene-3,17-dione (androstenedione) and its association with prostate cancer risk among subjects who participated in the Prostate Cancer Prevention Trial (PCPT). Methods We analyzed serum androstenedione levels in 317 prostate cancer cases and 353 controls, nested in the Prostate Cancer Prevention Trial (PCPT), a randomized, placebo-controlled trial that found finasteride decreased prostate cancer risk. Androstenedione is the second most important circulating androgen in men beside testosterone and also a substrate for 5α-reductase enzyme. Results We observed 22% increase in andostenedione levels compared to baseline values in subjects who were treated with finasteride for 3 years. This significant increase did not vary by case-control status. Adjusted OR and 95% CI for the 3rd tertile of absolute change of androstenedione levels compared to the 1st tertile was 0.42 (95% CI 0.19–0.94) for low-grade (Gleason <7) cases. Similar results were observed when analyzed using percent change. There were no significant associations between serum androstenedione levels and risk of high-grade disease. Conclusions The results of this nested case-control study confirm that finasteride blocks the conversion of testosterone to DHT and of androstenedione to 5α-androstanedione-3, 17-dione, which also leads to reduction of DHT formation. This decrease in DHT may help reduce the risk of low-grade prostate cancer in men. Our data on a differential effect of androstenedione also suggest that some high-grade prostate cancers may not require androgen for progression. PMID:25733274

  20. Effect of finasteride on serum androstenedione and risk of prostate cancer within the prostate cancer prevention trial: differential effect on high- and low-grade disease.

    PubMed

    Hoque, Ashraful; Yao, Song; Till, Cathee; Kristal, Alan R; Goodman, Phyllis J; Hsing, Ann W; Tangen, Catherine M; Platz, Elizabeth A; Stanczyk, Frank Z; Reichardt, Juergen K V; vanBokhoven, Adrie; Neuhouser, Marian L; Santella, Regina M; Figg, William D; Price, Douglas K; Parnes, Howard L; Lippman, Scott M; Ambrosone, Christine B; Thompson, Ian M

    2015-03-01

    To evaluate the effect of finasteride on serum androst-4-ene-3,17-dione (androstenedione) and its association with prostate cancer risk among subjects who participated in the Prostate Cancer Prevention Trial. We analyzed serum androstenedione levels in 317 prostate cancer cases and 353 controls, nested in the Prostate Cancer Prevention Trial, a randomized placebo-controlled trial that found finasteride decreased prostate cancer risk. Androstenedione is the second most important circulating androgen in men besides testosterone and also a substrate for 5α-reductase enzyme. We observed a 22% increase in androstenedione levels compared with the baseline values in subjects who were treated with finasteride for 3 years. This significant increase did not vary by case-control status. Adjusted odds ratio and 95% confidence interval for the third tertile of absolute change in androstenedione levels compared with the first tertile were 0.42 (95% confidence interval, 0.19-0.94) for low-grade (Gleason score <7) cases. Similar results were observed when analyzed using percent change. There were no significant associations between serum androstenedione levels and the risk of high-grade disease. The results of this nested case-control study confirm that finasteride blocks the conversion of testosterone to dihydrotestosterone (DHT) and of androstenedione to 5α-androstanedione-3,17-dione, which also leads to the reduction of DHT formation. This decrease in DHT may help reduce the risk of low-grade prostate cancer in men. Our data on a differential effect of androstenedione also suggest that some high-grade prostate cancers may not require androgen for progression. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Genetics Home Reference: prostate cancer

    MedlinePlus

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

  2. Hormone therapy for prostate cancer

    MedlinePlus

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

  3. Denosumab Reduces Risk of Bone Side Effects in Advanced Prostate Cancer

    Cancer.gov

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

  4. A review of clinical effects associated with metabolic syndrome and exercise in prostate cancer patients

    PubMed Central

    Kiwata, J L; Dorff, T B; Schroeder, E T; Gross, M E; Dieli-Conwright, C M

    2016-01-01

    Androgen deprivation therapy (ADT), a primary treatment for locally advanced or metastatic prostate cancer, is associated with the adverse effects on numerous physiologic parameters, including alterations in cardiometabolic variables that overlap with components of the metabolic syndrome (MetS). As MetS is an established risk factor for cardiovascular mortality and treatment for prostate cancer has been associated with the development of MetS, interventions targeting cardiometabolic factors have been investigated in prostate cancer patients to attenuate the detrimental effects of ADT. Much support exists for exercise interventions in improving MetS variables in insulin-resistant adults, but less evidence is available in men with prostate cancer. Regular exercise, when performed at appropriate intensities and volumes, can elicit improvements in ADT-related adverse effects, including MetS, and contributes to the growing body of literature supporting the role of exercise in cancer survivorship. This review (1) discusses the biologic inter-relationship between prostate cancer, ADT and MetS, (2) evaluates the current literature in support of exercise in targeting MetS and (3) describes the physiological mechanisms by which exercise may favorably alter MetS risk factors in prostate cancer patients on ADT. PMID:27349496

  5. Selenoproteins and Prostate Cancer

    DTIC Science & Technology

    2006-11-01

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

  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. Evaluation of ecological and in vitro effects of boron on prostate cancer risk (United States).

    PubMed

    Barranco, Wade T; Hudak, Paul F; Eckhert, Curtis D

    2007-02-01

    To determine: (1) the correlation of prostate cancer incidence and mortality with groundwater boron and selenium concentrations; and (2) the impact of boron on prostate cancer cell proliferation during co-treatment with alternative chemo-preventative agents, along with boron pre-treatment effects on cell sensitivity to ionizing radiation. For regression analysis, data on prostate cancer incidence and mortality were obtained from the Texas Cancer Registry, while groundwater boron and selenium concentrations were derived from the Texas Water Development Board. Cultured DU-145 prostate cancer cells were used to assess the impact of boric acid on cell proliferation when applied in combination with selenomethionine and genistein, or preceding radiation exposure. Groundwater boron levels correlated with a decrease in prostate cancer incidence (R = 0.6) and mortality (R = 0.6) in state planning regions, whereas selenium did not (R = 0.1; R = 0.2). Growth inhibition was greater during combined treatments of boric acid and selenomethionine, or boric acid and genistein, versus singular treatments. 8-day boric acid pre-exposure enhanced the toxicity of ionizing radiation treatment, while dose-dependently decreasing the expression of anti-apoptotic protein Bcl-2. Increased groundwater boron concentrations, across the state of Texas, correlate with reduced risk of prostate cancer incidence and mortality. Also, boric acid improves the anti-proliferative effectiveness of chemo-preventative agents, selenomethionine and genistein, while enhancing ionizing radiation cell kill.

  8. 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

  9. Inhibition of microRNA-500 has anti-cancer effect through its conditional downstream target of TFPI in human prostate cancer.

    PubMed

    Cai, Bing; Chen, Wei; Pan, Yue; Chen, Hongde; Zhang, Yirong; Weng, Zhiliang; Li, Yeping

    2017-07-01

    We investigated the prognostic potential and regulatory mechanism of microRNA-500 (miR-500), and human gene of tissue factor pathway inhibitor (TFPI) in prostate cancer. MiR-500 expression was assessed by qRT-PCR in prostate cancer cell lines and primary tumors. Cancer patients' clinicopathological factors and overall survival were analyzed according to endogenous miR-500 level. MiR-500 was downregulated in DU145 and VCaP cells. Its effect on prostate cancer proliferation, invasion in vitro, and tumorigenicity in vivo, were probed. Possible downstream target of miR-500, TFPI was assessed by luciferase assay and qRT-PCR in prostate cancer cells. In miR-500-downregulated DU145 and VCaP cells, TFPI was silenced to see whether it was directly involved in the regulation of miR-500 in prostate cancer. TFPI alone was either upregulated or downregulated in DU145 and VCaP cells. Their effect on prostate cancer development was further evaluated. MiR-500 is upregulated in both prostate cancer cells and primary tumors. In prostate cancer patients, high miR-500 expression is associated with poor prognosis and overall survival. In DU145 and VCaP cells, miR-500 downregulation inhibited cancer proliferation, invasion in vitro, and explant growth in vivo. TFPI was verified to be associated with miR-500 in prostate cancer. Downregulation of TFPI reversed anti-cancer effects of miR-500 downregulation in prostate cancer cells. However, neither TFPI upregulation nor downregulation alone had any functional impact on prostate cancer development. MiR-500 may be a potential biomarker and molecular target in prostate cancer. TFPI may conditionally regulate prostate cancer in miR-500-downregualted prostate cancer cells. © 2017 Wiley Periodicals, Inc.

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

    PubMed Central

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

    2016-01-01

    Stromal-epithelial interaction has been shown to promote local tumor growth and distant metastasis. We sought to create a promising gene therapy approach that co-targets cancer and its supporting stromal cells for combating castration-resistant prostate tumors. Herein, we demonstrated that human osteonectin is overexpressed in the prostate cancer epithelium and tumor stroma in comparison with their normal counterpart. We designed a novel human osteonectin promoter (hON-522E) containing positive transcriptional regulatory elements identified in both the promoter and exon 1 region of the human osteonectin gene. In vitro reporter assays revealed that the hON-522E promoter is highly active in androgen receptor negative and metastatic prostate cancer and bone stromal cells compared to androgen receptor-positive prostate cancer cells. Moreover, in vivo prostate-tumor–promoting activity of the hON-522E promoter was confirmed by intravenous administration of an adenoviral vector containing the hON-522E promoter-driven luciferase gene (Ad-522E-Luc) into mice bearing orthotopic human prostate tumor xenografts. In addition, an adenoviral vector with the hON-522E-promoter–driven herpes simplex virus thymidine kinase gene (Ad-522E-TK) was highly effective against the growth of androgen-independent human prostate cancer PC3M and bone stromal cell line in vitro and in pre-established PC3M tumors in vivo upon addition of the prodrug ganciclovir. Because of the heterogeneity of human prostate tumors, hON-522E promoter-mediated gene therapy has the potential for the treatment of hormone refractory and bone metastatic prostate cancers. PMID:27054343

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

    PubMed

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

    2016-01-01

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

  12. Fisetin Enhances Chemotherapeutic Effect of Cabazitaxel against Human Prostate Cancer Cells.

    PubMed

    Mukhtar, Eiman; Adhami, Vaqar Mustafa; Siddiqui, Imtiaz Ahmad; Verma, Ajit Kumar; Mukhtar, Hasan

    2016-12-01

    Although treatment of prostate cancer has improved over the past several years, taxanes, such as cabazitaxel, remain the only form of effective chemotherapy that improves survival in patients with metastatic castration-resistant prostate cancer. However, the effectiveness of this class of drugs has been associated with various side effects and drug resistance. We previously reported that fisetin, a hydroxyflavone, is a microtubule-stabilizing agent and inhibits prostate cancer cell proliferation, migration, and invasion and suggested its use as an adjuvant for treatment of prostate and other cancer types. In this study, we investigated the effect of fisetin in combination with cabazitaxel with the objective to achieve maximum therapeutic benefit, reduce dose and toxicity, and minimize or delay the induction of drug resistance and metastasis. Our data show for the first time that a combination of fisetin (20 μmol/L) enhances cabazitaxel (5 nmol/L) and synergistically reduces 22Rν1, PC-3M-luc-6, and C4-2 cell viability and metastatic properties with minimal adverse effects on normal prostate epithelial cells. In addition, the combination of fisetin with cabazitaxel was associated with inhibition of proliferation and enhancement of apoptosis. Furthermore, combination treatment resulted in the inhibition of tumor growth, invasion, and metastasis when assessed in two in vivo xenograft mouse models. These results provide evidence that fisetin may have therapeutic benefit for patients with advanced prostate cancer through enhancing the efficacy of cabazitaxel under both androgen-dependent and androgen-independent conditions. This study underscores the benefit of the combination of fisetin with cabazitaxel for the treatment of advanced and resistant prostate cancer and possibly other cancer types. Mol Cancer Ther; 15(12); 2863-74. ©2016 AACR. ©2016 American Association for Cancer Research.

  13. 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 ...

  14. Effect of dutasteride on the risk of prostate cancer.

    PubMed

    Andriole, Gerald L; Bostwick, David G; Brawley, Otis W; Gomella, Leonard G; Marberger, Michael; Montorsi, Francesco; Pettaway, Curtis A; Tammela, Teuvo L; Teloken, Claudio; Tindall, Donald J; Somerville, Matthew C; Wilson, Timothy H; Fowler, Ivy L; Rittmaster, Roger S

    2010-04-01

    We conducted a study to determine whether dutasteride reduces the risk of incident prostate cancer, as detected on biopsy, among men who are at increased risk for the disease. In this 4-year, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, we compared dutasteride, at a dose of 0.5 mg daily, with placebo. Men were eligible for inclusion in the study if they were 50 to 75 years of age, had a prostate-specific antigen (PSA) level of 2.5 to 10.0 ng per milliliter, and had had one negative prostate biopsy (6 to 12 cores) within 6 months before enrollment. Subjects underwent a 10-core transrectal ultrasound-guided biopsy at 2 and 4 years. Among 6729 men who underwent a biopsy or prostate surgery, cancer was detected in 659 of the 3305 men in the dutasteride group, as compared with 858 of the 3424 men in the placebo group, representing a relative risk reduction with dutasteride of 22.8% (95% confidence interval, 15.2 to 29.8) over the 4-year study period (P<0.001). Overall, in years 1 through 4, among the 6706 men who underwent a needle biopsy, there were 220 tumors with a Gleason score of 7 to 10 among 3299 men in the dutasteride group and 233 among 3407 men in the placebo group (P=0.81). During years 3 and 4, there were 12 tumors with a Gleason score of 8 to 10 in the dutasteride group, as compared with only 1 in the placebo group (P=0.003). Dutasteride therapy, as compared with placebo, resulted in a reduction in the rate of acute urinary retention (1.6% vs. 6.7%, a 77.3% relative reduction). The incidence of adverse events was similar to that in studies of dutasteride therapy for benign prostatic hyperplasia, except that in our study, as compared with previous studies, the relative incidence of the composite category of cardiac failure was higher in the dutasteride group than in the placebo group (0.7% [30 men] vs. 0.4% [16 men], P=0.03). Over the course of the 4-year study period, dutasteride reduced the risk of incident prostate

  15. Beneficial effects of tea and its polyphenols against prostate cancer.

    PubMed

    Siddiqui, Imtiaz A; Adhami, Vaqar M; Saleem, Mohammad; Mukhtar, Hasan

    2006-02-01

    Tea, next to water, is the most widely consumed beverage in the world. Depending upon the level of fermentation, tea can be categorized into three types: green (unfermented), oolong (partially fermented), and black (highly to fully fermented). In general, green tea has been found to be superior to black and oolong tea in terms of antioxidant and health promoting benefits owing to the higher content of (-)-epigallocatechin-3-gallate. Tea polyphenols comprise about one-third of the weight of the dried leaf, and they exhibit biochemical and pharmacological activities including antioxidant activities, inhibition of cell proliferation, induction of apoptosis, cell cycle arrest and modulation of carcinogen metabolism. Several studies demonstrate that most tea polyphenols exert their effects by scavenging reactive oxygen species (ROS) since excessive production of ROS has been implicated in the development of a variety of ailments including cancer of the prostate gland (CaP). Using cell culture and animal model systems, molecular targets for these remarkable beneficial effects of green tea drinking on CaP prevention and therapy have been defined. Geographical and case-control studies are showing that green tea drinking could afford CaP chemopreventive effects in human population. In this review we attempt to summarize the experimental as well as the epidemiological basis for the possible role of tea and its polyphenols for chemoprevention and chemotherapy of CaP.

  16. Quality of Life and Cost Effectiveness of Prostate Cancer Treatment

    DTIC Science & Technology

    2008-03-01

    61:120-128. 8. Cappelleri JC, Althof SE, Siegel RL, et al. Association between the erectile dysfunction inventory of treatment satisfaction and the...self-esteem and relationship questionnaire following treatment with sildenafil citrate for men with erectile dysfunction . Value in Health. 2005; 8...Inclusion and Exclusion criteria for CE Analysis Inclusion Criteria: (1) Patients must be treated for prostate cancer at the Hospital of the University of

  17. Quality of Life and Cost Effectiveness of Prostate Cancer Treatment

    DTIC Science & Technology

    2006-03-01

    Distribution Unlimited The views, opinions and/or findings contained in this report are...include comparison of efficiency and HRQoL for men with prostate cancer offered in two health care systems: Veterans Affairs (VA-public) and non-VA...uncertainty in the screening and treatment, debate on outcomes such as quality of life, satisfaction with care and cost of care continues. Our recent

  18. Effects of Radiation on Proteasome Function in Prostate Cancer Cells

    DTIC Science & Technology

    2011-02-01

    LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b. ABSTRACT U c. THIS PAGE U UU 13 19b...Radiation therapy plays an important role in the cure of prostate cancer. However, the outcome is limited by the existence of a highly radioresistant...lack of specific markers limited the outcome (Moscatelli et al. 2010; Richardson et al. 2004; Wang et al. 2009; Goldstein et al. 2010). Basal cells

  19. Nebraska Prostate Cancer Research Program

    DTIC Science & Technology

    2014-07-01

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

  20. Nebraska Prostate Cancer Research Program

    DTIC Science & Technology

    2012-05-01

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

  1. [Prostate cancer screening].

    PubMed

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

    2003-04-01

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

  2. Association between Biomarkers of Obesity and Risk of High-Grade Prostatic Intraepithelial Neoplasia and Prostate Cancer - Evidence of Effect Modification by Prostate Size

    PubMed Central

    Fowke, Jay H.; Motley, Saundra; Dai, Qi; Concepcion, Raoul; Barocas, Daniel A.

    2012-01-01

    Prostate enlargement is common with aging and obesity. We investigated the association between obesity and prostate cancer controlling for differential detection related to prostate enlargement. In an analysis of 500 men, we found body mass index, waist-hip ratio, and blood leptin levels were significantly associated with high-grade PC, but only among men without prostate enlargement. Leptin was also significantly associated with high-grade prostatic intraepithelial neoplasia (HGPIN) in the absence of prostate enlargement. Our results suggest obesity advances prostate carcinogenesis, and that detection biases at prostate biopsy may explain past inconsistencies in the association between obesity and PC. PMID:23079532

  3. Association between biomarkers of obesity and risk of high-grade prostatic intraepithelial neoplasia and prostate cancer--evidence of effect modification by prostate size.

    PubMed

    Fowke, Jay H; Motley, Saundra; Dai, Qi; Concepcion, Raoul; Barocas, Daniel A

    2013-01-28

    Prostate enlargement is common with aging and obesity. We investigated the association between obesity and prostate cancer controlling for differential detection related to prostate enlargement. In an analysis of 500 men, we found body mass index, waist-hip ratio, and blood leptin levels were significantly associated with high-grade PC, but only among men without prostate enlargement. Leptin was also significantly associated with high-grade prostatic intraepithelial neoplasia (HGPIN) in the absence of prostate enlargement. Our results suggest obesity advances prostate carcinogenesis, and that detection biases at prostate biopsy may explain past inconsistencies in the association between obesity and PC. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. Prostate Cancer Biorepository Network

    DTIC Science & Technology

    2015-10-01

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

  5. 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 ...

  6. Photosensitizers in prostate cancer therapy

    PubMed Central

    Gheewala, Taher; Skwor, Troy; Munirathinam, Gnanasekar

    2017-01-01

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

  7. Anticancer effects of ethanolic neem leaf extract on prostate cancer cell line (PC-3).

    PubMed

    Kumar, Suresh; Suresh, P K; Vijayababu, M R; Arunkumar, A; Arunakaran, J

    2006-04-21

    Prostate cancer (PC) is the most prevalent cancer and the leading cause of male cancer death. Azadirachta indica (neem tree) has been used successfully centuries to reduce tumors by herbalists throughout Southeast Asia. Here the present study indicated that an ethanolic extract of neem has been shown to cause cell death of prostate cancer cells (PC-3) by inducing apoptosis as evidenced by a dose-dependent increase in DNA fragmentation and a decrease in cell viability. Western blot studies indicated that treatment with neem extract showed decreased level of Bcl-2, which is anti-apoptotic protein and increased the level of Bax protein. So the neem extract could be potentially effective against prostate cancer treatment.

  8. [Benign prostatic hypertrophy and prostate cancer].

    PubMed

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

    2014-01-01

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

  9. Biomarkers for prostate cancer.

    PubMed

    Leman, Eddy S; Getzenberg, Robert H

    2009-09-01

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

  10. 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

  11. Antagonizing effects of membrane-acting androgens on the eicosanoid receptor OXER1 in prostate cancer

    PubMed Central

    Kalyvianaki, Konstantina; Gebhart, Veronika; Peroulis, Nikolaos; Panagiotopoulou, Christina; Kiagiadaki, Fotini; Pediaditakis, Iosif; Aivaliotis, Michalis; Moustou, Eleni; Tzardi, Maria; Notas, George; Castanas, Elias; Kampa, Marilena

    2017-01-01

    Accumulating evidence during the last decades revealed that androgen can exert membrane initiated actions that involve signaling via specific kinases and the modulation of significant cellular processes, important for prostate cancer cell growth and metastasis. Results of the present work clearly show that androgens can specifically act at the membrane level via the GPCR oxoeicosanoid receptor 1 (OXER1) in prostate cancer cells. In fact, OXER1 expression parallels that of membrane androgen binding in prostate cancer cell lines and tumor specimens, while in silico docking simulation of OXER1 showed that testosterone could bind to OXER1 within the same grove as 5-OxoETE, the natural ligand of OXER1. Interestingly, testosterone antagonizes the effects of 5-oxoETE on specific signaling pathways and rapid effects such as actin cytoskeleton reorganization that ultimately can modulate cell migration and metastasis. These findings verify that membrane-acting androgens exert specific effects through an antagonistic interaction with OXER1. Additionally, this interaction between androgen and OXER1, which is an arachidonic acid metabolite receptor expressed in prostate cancer, provides a novel link between steroid and lipid actions and renders OXER1 as new player in the disease. These findings should be taken into account in the design of novel therapeutic approaches in prostate cancer. PMID:28290516

  12. 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 ...

  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. 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.

  15. 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.

  16. Effect of Baliospermum montanum nanomedicine apoptosis induction and anti-migration of prostate cancer cells.

    PubMed

    Cherian, Aleena Mary; Snima, K S; Kamath, C Ravindranath; Nair, Shantikumar V; Lakshmanan, Vinoth-Kumar

    2015-04-01

    Prostate cancer has been diagnosed as the second most frequent and the sixth among the cancer causing deaths among men worldwide. There is a limited scope for the prevalent therapies as prostate cancer advances and they present adverse aftermaths that have put way for us to delve into naturally available anticancer agents. The main objective of the present work is to compile the advantages of ayurvedic herbal formulations with modern technology. Baliospermum montanum is a plant that is used in ayurveda for the treatment of cancer and the plant is studied to possess various constituents in it that are responsible for its anticancer activity. Stable nanoparticles of B. montanum were prepared from both the aqueous and ethanolic extracts of the plant and its cytotoxic effects were studied on prostate cancer and normal cell lines. Size analysis by DLS and SEM revealed the average size of nanoparticles prepared was 100±50 nm and 150±50 nm for the nanoparticles prepared from aqueous and ethanolic extract respectively. In vitro cytotoxicity showed a concentration and time dependent toxicity on prostate cancer cells with cell viability of 22% and 6% with maximum concentration of aqueous and ethanolic nanoparticles respectively, in 48 h. In vitro hemolysis assay confirmed that the prepared nanoparticles were compatible with blood with no occurrence of hemolysis. The nanoparticles showed a significant reduction in the colony forming ability and wound healing capacity of the prostate cancer cells. These studies hold the anti cancer potential of the B. montanum nanoparticles making it an important candidate for prostate cancer therapy.

  17. Preventing and Treating Prostate Cancer Spread to Bone

    MedlinePlus

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

  18. PROACT: Iterative Design of a Patient-Centered Visualization for Effective Prostate Cancer Health Risk Communication.

    PubMed

    Hakone, Anzu; Harrison, Lane; Ottley, Alvitta; Winters, Nathan; Gutheil, Caitlin; Han, Paul K J; Chang, Remco

    2017-01-01

    Prostate cancer is the most common cancer among men in the US, and yet most cases represent localized cancer for which the optimal treatment is unclear. Accumulating evidence suggests that the available treatment options, including surgery and conservative treatment, result in a similar prognosis for most men with localized prostate cancer. However, approximately 90% of patients choose surgery over conservative treatment, despite the risk of severe side effects like erectile dysfunction and incontinence. Recent medical research suggests that a key reason is the lack of patient-centered tools that can effectively communicate personalized risk information and enable them to make better health decisions. In this paper, we report the iterative design process and results of developing the PROgnosis Assessment for Conservative Treatment (PROACT) tool, a personalized health risk communication tool for localized prostate cancer patients. PROACT utilizes two published clinical prediction models to communicate the patients' personalized risk estimates and compare treatment options. In collaboration with the Maine Medical Center, we conducted two rounds of evaluations with prostate cancer survivors and urologists to identify the design elements and narrative structure that effectively facilitate patient comprehension under emotional distress. Our results indicate that visualization can be an effective means to communicate complex risk information to patients with low numeracy and visual literacy. However, the visualizations need to be carefully chosen to balance readability with ease of comprehension. In addition, due to patients' charged emotional state, an intuitive narrative structure that considers the patients' information need is critical to aid the patients' comprehension of their risk information.

  19. Molecular therapeutics in prostate cancer.

    PubMed

    Nicholson, B; Theodorescu, D

    2003-01-01

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

  20. Height and Prostate Cancer Risk

    PubMed Central

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

    2008-01-01

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

  1. Metabolic imbalance and prostate cancer progression

    PubMed Central

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

    2010-01-01

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

  2. 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.

  3. 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 ...

  4. Combined effects of atorvastatin and aspirin on growth and apoptosis in human prostate cancer cells.

    PubMed

    He, Yan; Huang, Huarong; Farischon, Chelsea; Li, Dongli; Du, Zhiyun; Zhang, Kun; Zheng, Xi; Goodin, Susan

    2017-02-01

    Epidemiologic studies indicate the use of either statins or aspirin have beneficial effects in prostate cancer patients. The present study was undertaken to evaluate the effects and mechanisms of atorvastatin and aspirin alone or in combination in human prostate cancer cells cultured in vitro and grown as xenograft tumors in severe combined immune-deficient (SCID) mice. The growth and apoptosis in prostate cancer cells were determined by the trypan blue exclusion and propidium iodide staining assays. Activation of the nuclear factor κB (NF-κB) was measured by luciferase reporter assay, and the levels of phospho-signal transducer and activator of transcription (Stat)3 and phospho-extracellular signal-regulated kinase (Erk)1/2 were determined by western blot analysis. Mice were injected subcutaneously with PC-3 cells in Matrigel. After 4-6 weeks, mice with PC-3 tumors received i.p. injections of vehicle, atorvastatin (5 mg/kg), aspirin (80 mg/kg), or atorvastatin (5 mg/kg) + aspirin (80 mg/kg) three times a week for 30 days. Our results demonstrated the combination of atorvastatin and aspirin had more potent effects on growth inhibition and apoptosis stimulation in prostate cancer cells than either drug alone. Mechanistic studies indicated the induction of apoptosis in PC-3 cells was associated with strong inhibition of NF-κB and decreases in the levels of phospho-Stat3 and phospho-Erk1/2. Results of the present study demonstrated a strong combined effect of atorvastatin and aspirin on inhibiting the growth of prostate cancer cells in vitro and in vivo. The findings provide a strong rationale for clinical evaluation of the combination of atorvastatin and aspirin in patients with prostate cancer.

  5. Potent anti-cancer effects of citrus peel flavonoids in human prostate xenograft tumors.

    PubMed

    Lai, Ching-Shu; Li, Shiming; Miyauchi, Yutaka; Suzawa, Michiko; Ho, Chi-Tang; Pan, Min-Hsiung

    2013-06-01

    Prostate cancer is one of the most prevalent malignancies and is the second leading cause of cancer-related deaths in men. Fruit and vegetable consumption is a novel, non-toxic therapeutic approach that can be used to prevent and treat prostate cancer. Citrus peels and their extracts have been reported to have potent pharmacological activities and health benefits due to the abundance of flavonoids in citrus fruits, particularly in the peels. Our previous studies demonstrated that oral administration of Gold Lotion (GL), an extract of multiple varieties of citrus peels containing abundant flavonoids, including a large percentage of polymethoxyflavones (PMFs), effectively suppressed azoxymethane (AOM)-induced colonic tumorigenesis. However, the efficacy of GL against prostate cancer has not yet been investigated. Here, we explored the anti-tumor effects of GL using a human prostate tumor xenograft mouse model. Our data demonstrated that treatment with GL by both intraperitoneal (i.p.) injection and oral administration dramatically reduced both the weights (57%-100% inhibition) and volumes (78%-94% inhibition) of the tumors without any observed toxicity. These inhibitory effects were accompanied by mechanistic down-regulation of the protein levels of inflammatory enzymes (inducible nitric oxide synthase, iNOS and cyclooxygenase-2, COX-2), metastasis (matrix metallopeptidase-2, MMP-2 and MMP-9), angiogenesis (vascular endothelial growth factor, VEGF), and proliferative molecules, as well as by the induction of apoptosis in prostate tumors. Our findings suggest that GL is an effective anti-cancer agent that may potentially serve as a novel therapeutic option for prostate cancer treatment.

  6. Plant-derived SAC domain of PAR-4 (Prostate Apoptosis Response 4) exhibits growth inhibitory effects in prostate cancer cells

    PubMed Central

    Sarkar, Shayan; Jain, Sumeet; Rai, Vineeta; Sahoo, Dipak K.; Raha, Sumita; Suklabaidya, Sujit; Senapati, Shantibhusan; Rangnekar, Vivek M.; Maiti, Indu B.; Dey, Nrisingha

    2015-01-01

    The gene Par-4 (Prostate Apoptosis Response 4) was originally identified in prostate cancer cells undergoing apoptosis and its product Par-4 showed cancer specific pro-apoptotic activity. Particularly, the SAC domain of Par-4 (SAC-Par-4) selectively kills cancer cells leaving normal cells unaffected. The therapeutic significance of bioactive SAC-Par-4 is enormous in cancer biology; however, its large scale production is still a matter of concern. Here we report the production of SAC-Par-4-GFP fusion protein coupled to translational enhancer sequence (5′ AMV) and apoplast signal peptide (aTP) in transgenic Nicotiana tabacum cv. Samsun NN plants under the control of a unique recombinant promoter M24. Transgene integration was confirmed by genomic DNA PCR, Southern and Northern blotting, Real-time PCR, and Nuclear run-on assays. Results of Western blot analysis and ELISA confirmed expression of recombinant SAC-Par-4-GFP protein and it was as high as 0.15% of total soluble protein. In addition, we found that targeting of plant recombinant SAC-Par-4-GFP to the apoplast and endoplasmic reticulum (ER) was essential for the stability of plant recombinant protein in comparison to the bacterial derived SAC-Par-4. Deglycosylation analysis demonstrated that ER-targeted SAC-Par-4-GFP-SEKDEL undergoes O-linked glycosylation unlike apoplast-targeted SAC-Par-4-GFP. Furthermore, various in vitro studies like mammalian cells proliferation assay (MTT), apoptosis induction assays, and NF-κB suppression suggested the cytotoxic and apoptotic properties of plant-derived SAC-Par-4-GFP against multiple prostate cancer cell lines. Additionally, pre-treatment of MAT-LyLu prostate cancer cells with purified SAC-Par-4-GFP significantly delayed the onset of tumor in a syngeneic rat prostate cancer model. Taken altogether, we proclaim that plant made SAC-Par-4 may become a useful alternate therapy for effectively alleviating cancer in the new era. PMID:26500666

  7. [Effect of change to flutamide for prostate cancer patient who developed breast pain during bicalutamide treatment (BIP-F study)].

    PubMed

    Kitamura, Yuki; Okuno, Hiroshi; Sakura, Yuma; Manabe, Yumi; Masuda, Norihiko; Ito, Haruk; Mishina, Mutsuki; Taoka, Rikiya; Terai, Akito; Sugimoto, Mikio; Kakehi, Yoshiyuki

    2014-01-01

    In Japan, prostate cancer is treated with non-steroidal anti-androgen (flutamide and bicalutamide). Development of breast pain during bicalutamide treatment, in prostate cancer patients reduces their quality of life (QOL) and treatment compliance. We studied the safety and effectiveness of switching from bicalutamide to flutamide in 13 prostate cancer patients who developed breast pain during bicalutamide treatment. We estimated the change in breast pain using a face scale and the Expanded Prostate Cancer Index Composite (EPIC) and EPIC-hormone domain (HD) score. The switch to flutamide relieved breast pain in nine patients, had no effect in one patient, and increased breast pain in two patients. One patient dropped out. Furthermore, summary score and hormone function were improved with a significant difference in the EPIC-HD score. Switching to flutamide in prostate cancer patients who develop breast pain during bicalutamide is safe and effective.

  8. Prostate Cancer Pathology Resource Network

    DTIC Science & Technology

    2015-12-01

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

  9. Methylselenium and Prostate Cancer Apoptosis

    DTIC Science & Technology

    2005-02-01

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

  10. 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

  11. 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.

  12. 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.

  13. [Late effects following curative radiotherapy for prostate cancer].

    PubMed

    Fokdal, Lars U; Høyer, Morten

    2005-09-12

    In this study we report late bladder, gastrointestinal and sexual dysfunctions in 23 patients following radical radiotherapy (66Gy-70Gy/33-35fx, 5 fx/week) for prostate cancer. We interviewed the subjects by telephone and compared the results with those of 45 healthy population controls. In general, the patients' bladder function was well preserved. However, compared with the population controls, significantly more patients reported dysuria and hematuria. Twenty-six percent of the patients reported moderate distress from the gastrointestinal tract. Fecal urgency, incontinence and the use of sanitary pads, as well as diarrhoea, and blood and mucous were significantly more common among the patients. Thirty-nine percent of the patients reported moderate or worse distress upon sexual activity, and significantly more patients suffered from erectile impotence.

  14. Growth Inhibitory Effect of Low Fat Diet on Prostate Cancer Cells: Results of a Prospective, Randomized Dietary Intervention Trial in Men With Prostate Cancer

    PubMed Central

    Aronson, William J.; Barnard, R. James; Freedland, Stephen J.; Henning, Susanne; Elashoff, David; Jardack, Patricia M.; Cohen, Pinchas; Heber, David; Kobayashi, Naoko

    2011-01-01

    Purpose A high fat Western diet and sedentary lifestyle may predispose men to prostate cancer through changes in serum hormones and growth factors. We evaluated the effect of a low fat diet on serum factors affecting prostate cancer cell growth by performing a prospective, randomized dietary intervention trial in men with prostate cancer. Materials and Methods We randomized 18 men with prostate cancer who did not receive prior therapy to a low fat (15% kcal), high fiber, soy protein supplemented diet or a Western (40% kcal fat) diet for 4 weeks. Fasting serum was collected at baseline and after the intervention to measure prostate specific antigen, sex hormones, insulin, insulin-like growth factor I and II, insulin-like growth factor binding proteins, lipids and fatty acids. LNCaP cells (ATCC®) were cultured in medium containing pre-intervention and post-intervention human serum to assess the in vitro effect of the diet on prostate cancer cell proliferation. Results Subjects in each group were highly compliant with the dietary intervention. Serum from men in the low fat group significantly decreased the growth of LNCaP cells relative to Western diet serum (p = 0.03). There were no significant between group changes in serum prostate specific antigen, sex hormones, insulin, insulin-like growth factor I and II, and insulin-like growth factor binding proteins. Serum triglyceride and linoleic acid (ω-6) levels were decreased in the low fat group (p = 0.034 and 0.005, respectively). Correlation analysis revealed that decreased ω-6 and increased ω-3 fatty acid correlated with decreased serum stimulated LNCaP cell growth (r = 0.64, p = 0.004 and r = −0.49, p = 0.04, respectively). Conclusions In this prospective, randomized dietary intervention trial a low fat diet resulted in changes in serum fatty acid levels that were associated with decreased human LNCaP cancer cell growth. Further prospective trials are indicated to evaluate the potential of low fat diets for

  15. Comparative effectiveness of alternative PSA-based prostate cancer screening strategies

    PubMed Central

    Gulati, Roman; Gore, John L.; Etzioni, Ruth

    2013-01-01

    Background The US Preventive Services Task Force recently concluded that the harms of existing prostate-specific antigen (PSA) screening strategies outweigh benefits. Objective To evaluate comparative effectiveness of alternative PSA screening strategies. Design Microsimulation model of prostate cancer incidence and mortality quantifying harms and lives saved for alternative PSA screening strategies. Data Sources National and trial data on PSA growth, screening and biopsy patterns, incidence, treatment distributions, treatment efficacy, and mortality. Target Population A contemporary cohort of US men. Time Horizon Lifetime. Perspective Societal. Intervention 35 screening strategies that vary by start/stop ages, inter-screening intervals, and thresholds for biopsy referral. Outcome Measurements PSA tests, false positive tests, cancers detected, overdiagnoses, prostate cancer deaths, lives saved, and months of life saved. Results of Base-Case Analysis Without screening, the risk of prostate cancer death is 2.86%. A reference strategy that screens men aged 50–74 annually with a PSA threshold for biopsy referral of 4 μg/L reduces the risk of prostate cancer death to 2.15% with risk of overdiagnosis of 3.3%. A strategy that uses higher PSA thresholds for biopsy referral in older men achieves a similar risk of prostate cancer death (2.23%) but reduces the risk of overdiagnosis to 2.3%. A strategy that screens biennially with longer inter-screen intervals for men with low PSA levels achieves similar risks of prostate cancer death (2.27%) and overdiagnosis (2.4%) but reduces total tests by 59% and false positive tests by 50%. Results of Sensitivity Analysis Varying incidence inputs or reducing the survival improvement due to screening did not change conclusions. Limitations The model is a simplification of prostate cancer natural history, and the survival improvement due to screening is uncertain. Conclusions PSA screening strategies that use higher thresholds for

  16. 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.

  17. 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 ...

  18. High-Dose-Rate Monotherapy: Safe and Effective Brachytherapy for Patients With Localized Prostate Cancer

    SciTech Connect

    Demanes, D. Jeffrey; Martinez, Alvaro A.; Ghilezan, Michel; Hill, Dennis R.; Schour, Lionel; Brandt, David; Gustafson, Gary

    2011-12-01

    Purpose: High-dose-rate (HDR) brachytherapy used as the only treatment (monotherapy) for early prostate cancer is consistent with current concepts in prostate radiobiology, and the dose is reliably delivered in a prospectively defined anatomic distribution that meets all the requirements for safe and effective therapy. We report the disease control and toxicity of HDR monotherapy from California Endocurietherapy (CET) and William Beaumont Hospital (WBH) in low- and intermediate-risk prostate cancer patients. Methods and Materials: There were 298 patients with localized prostate cancer treated with HDR monotherapy between 1996 and 2005. Two biologically equivalent hypofractionation protocols were used. At CET the dose was 42 Gy in six fractions (two implantations 1 week apart) delivered to a computed tomography-defined planning treatment volume. At WBH the dose was 38 Gy in four fractions (one implantation) based on intraoperative transrectal ultrasound real-time treatment planning. The bladder, urethral, and rectal dose constraints were similar. Toxicity was scored with the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 5.2 years. The median age of the patients was 63 years, and the median value of the pretreatment prostate-specific antigen was 6.0 ng/mL. The 8-year results were 99% local control, 97% biochemical control (nadir +2), 99% distant metastasis-free survival, 99% cause-specific survival, and 95% overall survival. Toxicity was scored per event, meaning that an individual patient with more than one symptom was represented repeatedly in the morbidity data table. Genitourinary toxicity consisted of 10% transient Grade 2 urinary frequency or urgency and 3% Grade 3 episode of urinary retention. Gastrointestinal toxicity was <1%. Conclusions: High disease control rates and low morbidity demonstrate that HDR monotherapy is safe and effective for patients with localized prostate cancer.

  19. Molecular Effects of 13C/DIM in Prostate Cancer

    DTIC Science & Technology

    2007-04-01

    with mutant Akt; Akt-Myr: transfected with constitutively activated Akt; Emp- v : transfected with empty vector; *: p ɘ.05; n=2) b IM and I3C could...Akt; Emp- V : transfected with empty vector, pLNCX; *: p ɘ.05; n=2). selective inhibitory effect of DIM on NF-kappaB DNA- binding activity in prostate...also extracted and subjected to measurement of NF-nB DNA-binding activity using the EMSA method described above. The protein expressions of AR, p -AR

  20. Use of testosterone replacement therapy in the United States and its effect on subsequent prostate cancer outcomes.

    PubMed

    Kaplan, Alan L; Hu, Jim C

    2013-08-01

    To assess utilization trends and determine the effect of testosterone replacement therapy on outcomes in men who subsequently developed prostate cancer. We used linked Surveillance, Epidemiology, and End Results-Medicare data to identify 149,354 men diagnosed with prostate cancer from 1992 to 2007. Of those, 2,237 men (1.5%) underwent testosterone replacement therapy before their prostate cancer diagnosis. Propensity scoring methods were used to assess cancer-specific outcomes of testosterone replacement vs no replacement therapy. Testosterone replacement was associated with older age at cancer diagnosis, nonwhite race, and higher comorbidity (P <.001). No testosterone vs testosterone before the prostate cancer diagnosis was associated with higher grade (34% vs 30%, P <.0001) and more T4 (6.5% vs 4.3%, P <.0001) tumors. Mortality was decreased in men with ≥2 prostate-specific antigen (PSA) tests in the year before their cancer diagnosis. No significant difference was found between groups in overall survival, cancer-specific survival, or use of salvage androgen-deprivation therapy after initial treatment. Through our observational study design, we show that testosterone use was low throughout the study period. Testosterone use was not associated with aggressive prostate cancer and did not affect overall or disease-specific mortality. Although our findings support growing evidence that testosterone replacement is safe with respect to prostate cancer, confirmatory prospective studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. The Effect of Start and Stop Age at Screening on the Risk of Being Diagnosed with Prostate Cancer.

    PubMed

    Godtman, Rebecka Arnsrud; Carlsson, Sigrid; Holmberg, Erik; Stranne, Johan; Hugosson, Jonas

    2016-05-01

    We investigated the effect of age and number of screens on the risk of prostate cancer diagnosis. Since 1995 the Göteborg randomized population based prostate cancer screening trial has invited men biennially for prostate specific antigen testing, until the upper age limit of 70 years. Men with a prostate specific antigen above the threshold of 2.5 ng/ml were recommended further evaluation including 10-core biopsy (sextant before 2009). The present study comprises 9,065 men born between 1930 and 1943 (1944 excluded due to different screening algorithm). Complete attendees were defined as men who accepted all screening invitations (maximum 3 to 9 invitations). The cumulative incidence of prostate cancer was calculated using standard methods. Of the 3,488 (38%) complete attendees 667 were diagnosed with prostate cancer (followup 1995 to June 30, 2014). At age 70 years there was no significant difference in prostate cancer risk among those who started screening at the age of 52 (9 screens), 55 (7 screens) or 60 (5 screens) years. However, the cumulative risk of prostate cancer diagnosis increased dramatically with age, and was 7.9% at age 60, 15% at age 65 and 21% at age 70 for men who had been screened 4 or more times. There was no clear association between risk of prostate cancer and the number of screens. Starting screening at an early age appears to advance the time of prostate cancer diagnosis but does not seem to increase the risk of being diagnosed with the disease. Age at termination of screening is strongly associated with the risk of being diagnosed with prostate cancer. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. [Surgery of prostate cancer].

    PubMed

    Villers, Arnauld; Rébillard, Xavier

    2003-12-31

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

  3. 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.

  4. Hydrogen sulfide mediates the anti-survival effect of sulforaphane on human prostate cancer cells

    SciTech Connect

    Pei, Yanxi; Wu, Bo; Cao, Qiuhui; Wu, Lingyun; Yang, Guangdong

    2011-12-15

    Hydrogen sulfide (H{sub 2}S) is a novel gasotransmitter that regulates cell proliferation and other cellular functions. Sulforaphane (SFN) is a sulfur-containing compound that exhibits anticancer properties, and young sprouts of broccoli are particularly rich in SFN. There is consistent epidemiological evidence that the consumption of sulfur-containing vegetables, such as garlic and cruciferous vegetables, may help reduce the occurrence of prostate cancer. Here we found that a large amount of H{sub 2}S is released when SFN is added into cell culture medium or mixed with mouse liver homogenates, respectively. Both SFN and NaHS (a H{sub 2}S donor) decreased the viability of PC-3 cells (a human prostate cancer cell line) in a dose-dependent manner, and supplement of methemoglobin or oxidized glutathione (two H{sub 2}S scavengers) reversed SFN-reduced cell viability. We further found both cystathionine gamma-lyase (CSE) and cystathionine beta-synthase are expressed in PC-3 cells and mouse prostate tissues. H{sub 2}S production in prostate tissues from CSE knockout mice was only 20% of that from wild-type mice, suggesting CSE is a major H{sub 2}S-producing enzyme in prostate. CSE overexpression enhanced H{sub 2}S production and inhibited cell viability in PC-3 cells. In addition, both SFN and NaHS activated p38 mitogen-activated protein kinases (MAPK) and c-Jun N-terminal kinase (JNK). Pre-treatment of PC-3 cells with methemoglobin decreased SFN-stimulated MAPK activities. Suppression of both p38 MAPK and JNK reversed H{sub 2}S- or SFN-reduced viability of PC-3 cells. Our results demonstrated that H{sub 2}S mediates the inhibitory effect of SFN on the proliferation of PC-3 cells, which suggests that H{sub 2}S-releasing diet or drug might be beneficial in the treatment of prostate cancer. Highlights: Black-Right-Pointing-Pointer A large amount of H{sub 2}S is released from sulforaphane. Black-Right-Pointing-Pointer H{sub 2}S mediates the anti-survival effect of

  5. 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.

  6. Overview of Dietary Supplements in Prostate Cancer.

    PubMed

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

    2016-11-01

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

  7. Oral selenium supplementation has no effect on prostate-specific antigen velocity in men undergoing active surveillance for localized prostate cancer.

    PubMed

    Stratton, M Suzanne; Algotar, Amit M; Ranger-Moore, James; Stratton, Steven P; Slate, Elizabeth H; Hsu, Chiu-Hsieh; Thompson, Patricia A; Clark, Larry C; Ahmann, Frederick R

    2010-08-01

    The Nutritional Prevention of Cancer trial showed a 52% lower incidence of prostate cancer in men supplemented with selenium. As a result, our study was designed to assess whether selenium supplementation attenuates the progression of prostate cancer. A phase 2 randomized, double-blind, placebo-controlled clinical trial was conducted in men with localized nonmetastatic prostate cancer who had elected to forgo active treatment and be followed by active surveillance. A total of 140 men were randomized to placebo (n = 46), 200 microg/d (n = 47), or 800 microg/d (n = 47) selenium p.o. (as selenized yeast) and followed every 3 months for up to 5 years. Prostate-specific antigen (PSA) velocity was used as a marker of prostate cancer progression and was estimated using mixed-effects regression. Adjusting for age, body mass index, baseline selenium, smoking, baseline PSA, race, PSA method, and Gleason score, PSA velocities for the 200 microg/d and 800 microg/d treatment groups were not statistically significantly different from placebo (P = 0.32 and P = 0.61, respectively). In the highest quartile of baseline selenium, men supplemented with 800 microg selenium showed statistically significantly higher PSA velocity as compared with placebo (P = 0.018). Selenium supplementation did not show a protective effect on PSA velocity in subjects with localized prostate cancer. On the contrary, supplementation with high-dose selenium was observed to be a risk factor for increased PSA velocity in men with high baseline plasma selenium concentrations.

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

    PubMed

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

    2016-11-22

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

  9. Dietary Antioxidants and Prostate Cancer: A Review

    PubMed Central

    Vance, Terrence M.; Su, Joseph; Fontham, Elizabeth T. H.; Koo, Sung I.; Chun, Ock K.

    2013-01-01

    Prostate cancer is the most common non-cutaneous cancer in men in the United States. Several studies have examined the relationship between prostate cancer and antioxidants; however, the results of these studies are inconsistent. This article provides a systematic review of studies on prostate cancer and antioxidant intake from diet and supplements. Tea and coffee appear to offer protection against advanced prostate cancer. Different forms of vitamin E appear to exert different effects on prostate cancer, with alpha-tocopherol potentially increasing and gamma-tocopherol potentially decreasing risk of the disease. There is no strong evidence for a beneficial effect of selenium, vitamin C, or beta-carotene, while lycopene appears to be negatively associated with risk of the disease. The effect of dietary antioxidants on prostate cancer remains undefined and inconclusive, with different antioxidants affecting prostate cancer risk differentially. Further studies are needed to clarify the relationship between antioxidants and prostate cancer risk and to delineate the underlying mechanisms. PMID:23909722

  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. Serum testosterone level predicts the effective time of androgen deprivation therapy in metastatic prostate cancer patients

    PubMed Central

    Wang, Yue; Dai, Bo; Ye, Ding-Wei

    2017-01-01

    Androgen deprivation therapy (ADT) is the standard of care for patients with metastatic prostate cancer. However, whether serum testosterone levels, using a cut-off point of 50 ng dl−1, are related to the effective time of ADT in newly diagnosed prostate cancer patients remains controversial. Moreover, recent studies have shown that some patients may benefit from the addition of upfront docetaxel chemotherapy. To date, no studies have been able to distinguish patients who will benefit from the combination of ADT and docetaxel chemotherapy. This study included 206 patients who were diagnosed with metastatic prostate cancer and showed progression to castrate-resistance prostate cancer (CRPC). Serum testosterone levels were measured prospectively after ADT for 1, 3, and 6 months. The endpoint was the time to CRPC. In univariate and multivariate analyses, testosterone levels <50 ng dl−1 were not associated with the effective time of ADT. Receiver operating characteristic and univariate analysis showed that testosterone levels of ≤25 ng dl−1 after the first month of ADT offered the best overall sensitivity and specificity for prediction of a longer time to CRPC (adjusted hazard ratio [HR], 1.46; 95% confidence interval [95% CI], 1.08–1.96; P = 0.013). Our results show that serum testosterone level of 25 ng dl−1 plays a prognostic role in prostate cancer patients receiving ADT. A testosterone value of 25 ng dl−1 after the first month of ADT can distinguish patients who benefit from ADT effectiveness for only a short time. These patients may need to receive ADT and concurrent docetaxel chemotherapy. PMID:26975487

  12. Serum testosterone level predicts the effective time of androgen deprivation therapy in metastatic prostate cancer patients.

    PubMed

    Wang, Yue; Dai, Bo; Ye, Ding-Wei

    2017-01-01

    Androgen deprivation therapy (ADT) is the standard of care for patients with metastatic prostate cancer. However, whether serum testosterone levels, using a cut-off point of 50 ng dl-1 , are related to the effective time of ADT in newly diagnosed prostate cancer patients remains controversial. Moreover, recent studies have shown that some patients may benefit from the addition of upfront docetaxel chemotherapy. To date, no studies have been able to distinguish patients who will benefit from the combination of ADT and docetaxel chemotherapy. This study included 206 patients who were diagnosed with metastatic prostate cancer and showed progression to castrate-resistance prostate cancer (CRPC). Serum testosterone levels were measured prospectively after ADT for 1, 3, and 6 months. The endpoint was the time to CRPC. In univariate and multivariate analyses, testosterone levels <50 ng dl-1 were not associated with the effective time of ADT. Receiver operating characteristic and univariate analysis showed that testosterone levels of ≤25 ng dl-1 after the first month of ADT offered the best overall sensitivity and specificity for prediction of a longer time to CRPC (adjusted hazard ratio [HR], 1.46; 95% confidence interval [95% CI], 1.08-1.96; P = 0.013). Our results show that serum testosterone level of 25 ng dl-1 plays a prognostic role in prostate cancer patients receiving ADT. A testosterone value of 25 ng dl-1 after the first month of ADT can distinguish patients who benefit from ADT effectiveness for only a short time. These patients may need to receive ADT and concurrent docetaxel chemotherapy.

  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. Review of selenium and prostate cancer prevention.

    PubMed

    Yang, Lei; Pascal, Mouracade; Wu, Xiao-Hou

    2013-01-01

    Prostate cancer is the most common malignancy in men in the United States. Surgery or radiation are sometimes unsatisfactory treatments because of the complications such as incontinence or erectile dysfunction. Selenium was found to be effective to prevent prostate cancer in the Nutritional Prevention of Cancer Trial (NPC), which motivated two other clinical trials: the Selenium and Vitamin E Cancer Prevention Trial (SELECT) and a Phase III trial of selenium to prevent prostate cancer in men with high-grade prostatic intraepithelial neoplasia. However, these two trials failed to confirm the results of the NPC trial and indicated that the selenium may not be preventive of prostate cancer. In this article we review the three clinical trials and discuss some different points which might be potential factors underlying variation in results obtained.

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

    PubMed Central

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

    2015-01-01

    Inflammation is associated with several diseases of the prostate including benign enlargement and cancer, but a causal relationship has not been established. Our objective was to characterize the prostate inflammatory microenvironment after infection with a human prostate-derived bacterial strain and to determine the effect of inflammation on prostate cancer progression. To this end, we mimicked typical human prostate infection with retrograde urethral instillation of CP1, a human prostatic isolate of Escherichia coli. CP1 bacteria were tropic for the accessory sex glands and induced acute inflammation in the prostate and seminal vesicles, with chronic inflammation lasting at least 1 year. Compared to controls, infection induced both acute and chronic inflammation with epithelial hyperplasia, stromal hyperplasia, and inflammatory cell infiltrates. In areas of inflammation, epithelial proliferation and hyperplasia often persist, despite decreased expression of androgen receptor (AR). Inflammatory cells in the prostates of CP1-infected mice were characterized at 8 weeks post-infection by flow cytometry, which showed an increase in macrophages and lymphocytes, particularly Th17 cells. Inflammation was additionally assessed in the context of carcinogenesis. Multiplex cytokine profiles of inflamed prostates showed that distinct inflammatory cytokines were expressed during prostate inflammation and cancer, with a subset of cytokines synergistically increased during concurrent inflammation and cancer. Furthermore, CP1 infection in the Hi-Myc mouse model of prostate cancer accelerated the development of invasive prostate adenocarcinoma, with 70% more mice developing cancer by 4.5 months of age. This study provides direct evidence that prostate inflammation accelerates prostate cancer progression and gives insight into the microenvironment changes induced by inflammation that may accelerate tumour initiation or progression. PMID:25348195

  16. 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

  17. Prostate Cancer-Specific and Potent Antitumor Effect of a DD3-Controlled Oncolytic Virus Harboring the PTEN Gene

    PubMed Central

    Ding, Miao; Cao, Xin; Xu, Hai-neng; Fan, Jun-kai; Huang, Hong-ling; Yang, Dong-qin; Li, Yu-hua; Wang, Jian; Li, Runsheng; Liu, Xin-Yuan

    2012-01-01

    Prostate cancer is a major health problem for men in Western societies. Here we report a Prostate Cancer-Specific Targeting Gene-Viro-Therapy (CTGVT-PCa), in which PTEN was inserted into a DD3-controlled oncolytic viral vector (OV) to form Ad.DD3.E1A.E1B(Δ55)-(PTEN) or, briefly, Ad.DD3.D55-PTEN. The woodchuck post-transcriptional element (WPRE) was also introduced at the downstream of the E1A coding sequence, resulting in much higher expression of the E1A gene. DD3 is one of the most prostate cancer-specific genes and has been used as a clinical bio-diagnostic marker. PTEN is frequently inactivated in primary prostate cancers, which is crucial for prostate cancer progression. Therefore, the Ad.DD3.D55-PTEN has prostate cancer specific and potent antitumor effect. The tumor growth rate was almost completely inhibited with the final tumor volume after Ad.DD3.D55-PTEN treatment less than the initial volume at the beginning of Ad.DD3.D55-PTEN treatment, which shows the powerful antitumor effect of Ad.DD3.D55-PTEN on prostate cancer tumor growth. The CTGVT-PCa construct reported here killed all of the prostate cancer cell lines tested, such as DU145, 22RV1 and CL1, but had a reduced or no killing effect on all the non-prostate cancer cell lines tested. The mechanism of action of Ad.DD3.D55-PTEN was due to the induction of apoptosis, as detected by TUNEL assays and flow cytometry. The apoptosis was mediated by mitochondria-dependent and -independent pathways, as determined by caspase assays and mitochondrial membrane potential. PMID:22509396

  18. 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 ...

  19. [CCAFU Recommendations 2013: Prostate cancer].

    PubMed

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

    2013-11-01

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

  20. Delivering prostate cancer prevention messages to the public: how the National Cancer Institute (NCI) effectively spread the word about the Prostate Cancer Prevention Trial (PCPT) results.

    PubMed

    Croker, Kara Smigel; Ryan, Anne; Morzenti, Thuy; Cave, Lynn; Maze-Gallman, Tamara; Ford, Leslie

    2004-01-01

    The Prostate Cancer Prevention Trial was the first clinical trial to show that a direct intervention (5 mg of finasteride daily for 7 years) could reduce a man's risk of developing prostate cancer. Initial results also suggested that men taking finasteride had an increased risk of developing what appeared to be higher-grade disease (Gleason score 7-10). The National Cancer Institute has a congressional mandate to communicate health information to the public and has established methods to reach the public directly and to reach information intermediaries in the media, professional societies, and advocacy groups. The groundbreaking yet complicated results of the Prostate Cancer Prevention Trial were widely disseminated by National Cancer Institute using the social marketing and public-relations strategies and tactics detailed here. Copyright 2004 Elsevier Inc.

  1. TGF-β Effects on Prostate Cancer Cell Migration and Invasion Require FosB.

    PubMed

    Barrett, Cachétne S X; Millena, Ana C; Khan, Shafiq A

    2017-01-01

    Activator Protein-1 (AP-1) family (cJun, JunB, JunD, cFos, FosB, Fra1, and Fra2) plays a central role in the transcriptional regulation of many genes that are associated with cell proliferation, differentiation, migration, metastasis, and survival. Many oncogenic signaling pathways converge at the AP-1 transcription complex. Transforming growth factor beta (TGF-β) is a multifunctional regulatory cytokine that regulates many aspects of cellular function, including cellular proliferation, differentiation, migration, apoptosis, adhesion, angiogenesis, immune surveillance, and survival. This study investigated, the role of FOS proteins in TGF-β signaling in prostate cancer cell proliferation, migration, and invasion. Steady state expression levels of FOS mRNA and proteins were determined using RT-PCR and western blotting analyses. DU145 and PC3 prostate cancer cells were exposed to TGF-β1 at varying time and dosage, RT-PCR, western blot, and immunofluorescence analyses were used to determine TGF-β1 effect on FOS mRNA and protein expression levels as well as FosB subcellular localization. Transient silencing of FosB protein was used to determine its role in cell proliferation, migration, and invasion. Our data show that FOS mRNA and proteins were differentially expressed in human prostate epithelial (RWPE-1) and prostate cancer cell lines (LNCaP, DU145, and PC3). TGF-β1 induced the expression of FosB at both the mRNA and protein levels in DU145 and PC3 cells, whereas cFos and Fra1 were unaffected. Immunofluorescence analysis showed an increase in the accumulation of FosB protein in the nucleus of PC3 cells after treatment with exogenous TGF-β1. Selective knockdown of endogenous FosB by specific siRNA did not have any effect on cell proliferation in PC3 and DU145 cells. However, basal and TGF-β1- and EGF-induced cell migration was significantly reduced in DU145 and PC3 cells lacking endogenous FosB. TGF-β1- and EGF-induced cell invasion were also significantly

  2. Tomato-based randomized controlled trial in prostate cancer patients: Effect on PSA.

    PubMed

    Paur, Ingvild; Lilleby, Wolfgang; Bøhn, Siv Kjølsrud; Hulander, Erik; Klein, Willibrord; Vlatkovic, Ljiljana; Axcrona, Karol; Bolstad, Nils; Bjøro, Trine; Laake, Petter; Taskén, Kristin A; Svindland, Aud; Eri, Lars Magne; Brennhovd, Bjørn; Carlsen, Monica H; Fosså, Sophie D; Smeland, Sigbjørn S; Karlsen, Anette S; Blomhoff, Rune

    2017-06-01

    The effect of lycopene-containing foods in prostate cancer development remains undetermined. We tested whether a lycopene-rich tomato intervention could reduce the levels of prostate specific antigen (PSA) in prostate cancer patients. Prior to their curative treatment, 79 patients with prostate cancer were randomized to a nutritional intervention with either 1) tomato products containing 30 mg lycopene per day; 2) tomato products plus selenium, omega-3 fatty acids, soy isoflavones, grape/pomegranate juice, and green/black tea (tomato-plus); or 3) control diet for 3 weeks. The main analysis, which included patients in all risk categories, did not reveal differences in changes of PSA-values between the intervention and control groups. Post-hoc, exploratory analyses within intermediate risk (n = 41) patients based on tumor classification and Gleason score post-surgery, revealed that median PSA decreased significantly in the tomato group as compared to controls (-2.9% and +6.5% respectively, p = 0.016). In separate post-hoc analyses, we observed that median PSA-values decreased by 1% in patients with the highest increases in plasma lycopene, selenium and C20:5 n-3 fatty acid, compared to an 8.5% increase in the patients with the lowest increase in lycopene, selenium and C20:5 n-3 fatty acid (p = 0.003). Also, PSA decreased in patients with the highest increase in lycopene alone (p = 0.009). Three week nutritional interventions with tomato-products alone or in combination with selenium and n-3 fatty acids lower PSA in patients with non-metastatic prostate cancer. Our observation suggests that the effect may depend on both aggressiveness of the disease and the blood levels of lycopene, selenium and omega-3 fatty acids. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  3. Effect of Soy Protein Isolate Supplementation on Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy

    PubMed Central

    Bosland, Maarten C; Kato, Ikuko; Zeleniuch-Jacquotte, Anne; Schmoll, Joanne; Rueter, Erika Enk; Melamed, Jonathan; Xiangtian Kong, Max; Macias, Virgilia; Kajdacsy-Balla, Andre; Lumey, L. H.; Xie, Hui; Gao, Weihua; Walden, Paul; Lepor, Herbert; Taneja, Samir S.; Randolph, Carla; Schlicht, Michael J.; Meserve-Watanabe, Hiroko; Deaton, Ryan J.; Davies, Joanne A.

    2013-01-01

    IMPORTANCE Soy consumption has been suggested to reduce risk or recurrence of prostate cancer, but this has not been tested in a randomized trial with prostate cancer as the end point. OBJECTIVE To determine whether daily consumption of a soy protein isolate supplement for 2 years reduces the rate of biochemical recurrence of prostate cancer after radical prostatectomy or delays such recurrence. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind trial conducted from July 1997 to May 2010 at 7 US centers comparing daily consumption of a soy protein supplement vs placebo in 177 men at high risk of recurrence after radical prostatectomy for prostate cancer. Supplement intervention was started within 4 months after surgery and continued for up to 2 years, with prostate-specific antigen (PSA) measurements made at 2-month intervals in the first year and every 3 months thereafter. INTERVENTION Participants were randomized to receive a daily serving of a beverage powder containing 20 g of protein in the form of either soy protein isolate (n=87)or, as placebo, calcium caseinate (n=90). MAIN OUTCOMES AND MEASURES Biochemical recurrence rate of prostate cancer (defined as development of a PSA level of ≥0.07 ng/mL) over the first 2 years following randomization and time to recurrence. RESULTS The trial was stopped early for lack of treatment effects at a planned interim analysis with 81 evaluable participants in the intervention group and 78 in the placebo group. Overall, 28.3% of participants developed biochemical recurrence within 2 years of entering the trial (close to the a priori predicted recurrence rate of 30%). Among these, 22 (27.2%) occurred in the intervention group and 23 (29.5%) in the placebo group. The resulting hazard ratio for active treatment was 0.96 (95% CI, 0.53–1.72; log-rank P = .89). Adherence was greater than 90% and there were no apparent adverse events related to supplementation. CONCLUSION AND RELEVANCE Daily consumption of a beverage

  4. 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

  5. Effect of metabolic syndrome on pathologic features of prostate cancer.

    PubMed

    Kheterpal, Emil; Sammon, Jesse D; Diaz, Mireya; Bhandari, Akshay; Trinh, Quoc-Dien; Pokala, Naveen; Sharma, Pranav; Menon, Mani; Agarwal, Piyush K

    2013-10-01

    The prevalence of metabolic syndrome has been increasing worldwide, however its association with prostate cancer (CaP) is unclear. We reviewed patients undergoing robot assisted radical prostatectomy (RARP) to evaluate if those with metabolic syndrome had more aggressive disease. A prospective database of patients undergoing RARP between January 2005 and December 2008 (n = 2756) was queried for components of metabolic syndrome (BMI ≥ 30 and ≥ 2 of the following: hypertension, diabetes or elevated blood glucose, and dyslipidemia; n = 357). Patients with no components of metabolic syndrome were used as controls (n = 694). Biopsy and final pathology were compared between the 2 groups using all controls, and using best-matched controls (n = 357) based on greedy matching by propensity score. Compared with unmatched controls, metabolic syndrome patients had higher pathology Gleason grade (≥ 7: 78% vs. 64%, P < 0.001) and higher pathologic stage (≥ T3 disease: 43% vs. 31%, P < 0.001). After controlling for confounders, those with metabolic syndrome when compared with best-matched controls had maintained the greater pathology Gleason grade (≥ 7: 78% vs. 64%, P < 0.001) and pathologic stage (≥ T3 disease: 43% vs. 32%, P < 0.001). They also had significantly greater pathologic upgrading of Gleason grade 6 adenocarcinoma found on biopsy compared with best-matched controls (63% vs. 45%, P < 0.001). On pathology, a 2-fold increase in Gleason 8 and greater was noted between patients with metabolic syndrome and best-matched controls (15% vs. 8%). After controlling for confounders, patients with metabolic syndrome were found to have higher Gleason grade and tumor stage on final pathology and were more likely to have upgrading. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. 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.

  7. The effect of testosterone replacement therapy on prostate cancer: a systematic review and meta-analysis.

    PubMed

    Cui, Y; Zong, H; Yan, H; Zhang, Y

    2014-06-01

    Testosterone replacement therapy (TRT) is a widely accepted form of treatment worldwide for aging men with late-onset hypogonadism syndrome. Urologists have been concerned about the possibility of TRT causing prostate cancer. The aim of this study was to assess the relationship between TRT and prostate cancer. A literature review was performed to identify all published, randomized controlled trials (RCTs) of testosterone treatment for hypogonadism. The search included the MEDLINE, Embase and the Cochrane Controlled Trials Register databases. Fixed-effect model was chosen for homogeneous studies; otherwise, a random-effect model was used. Inconsistency was quantified by using the I2 statistic, which tests the proportion of heterogeneity across studies. Results of 22 RCTs involving a total of 2351 patients were analyzed. Eleven RCTs were short-term (<12 months) and 11 were long-term (12-36 months) comparisons of TRT with a placebo; TRT was administered transdermally, orally or by injection. Respective odds ratio (OR) and 95% confidence interval (CI) values for injection, transdermal administration and oral administration of short-term TRT were as follows: prostate cancer: 0.39 (0.06-2.45), 1.10 (0.26-4.65) and no oral; biopsy: 5.28 (0.24-113.87), 2.11 (0.32-13.73) and no oral; and prostate nodule: 1.01 (0.13-7.60), no injection and oral. Respective OR and 95% CI values for injection, transdermal administration and oral administration of long-term TRT were as follows: prostate cancer: 2.09 (0.18-24.73), 3.06 (0.12-76.70) and 0.19 (0.01-4.03); biopsy: 2.09 (0.18-24.73), 3.65 (0.88-15.20) and 0.97 (0.13-7.03); and prostate nodule: 3.13 (0.12-80.68), 1.00 (0.06-16.41) and 0.97 (0.13-7.03). Though for some routes of administration and some end points, the OR associated with testosterone administration were >1 indicating increased risk, none of these reached or even approached statistical significance (all P>0.10), which was consistent with the results of subgroup analyses

  8. Vitamin E and Prostate Cancer

    USDA-ARS?s Scientific Manuscript database

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

  9. [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.

  10. 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

  11. 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

  12. Equivalent dose and effective dose from stray radiation during passively scattered proton radiotherapy for prostate cancer

    NASA Astrophysics Data System (ADS)

    Fontenot, Jonas; Taddei, Phillip; Zheng, Yuanshui; Mirkovic, Dragan; Jordan, Thomas; Newhauser, Wayne

    2008-03-01

    Proton therapy reduces the integral therapeutic dose required for local control in prostate patients compared to intensity-modulated radiotherapy. One proposed benefit of this reduction is an associated decrease in the incidence of radiogenic secondary cancers. However, patients are also exposed to stray radiation during the course of treatment. The purpose of this study was to quantify the stray radiation dose received by patients during proton therapy for prostate cancer. Using a Monte Carlo model of a proton therapy nozzle and a computerized anthropomorphic phantom, we determined that the effective dose from stray radiation per therapeutic dose (E/D) for a typical prostate patient was approximately 5.5 mSv Gy-1. Sensitivity analysis revealed that E/D varied by ±30% over the interval of treatment parameter values used for proton therapy of the prostate. Equivalent doses per therapeutic dose (HT/D) in specific organs at risk were found to decrease with distance from the isocenter, with a maximum of 12 mSv Gy-1 in the organ closest to the treatment volume (bladder) and 1.9 mSv Gy-1 in the furthest (esophagus). Neutrons created in the nozzle predominated effective dose, though neutrons created in the patient contributed substantially to the equivalent dose in organs near the proton field. Photons contributed less than 15% to equivalent doses.

  13. 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

  14. Analysis of Morphogenic Effect of hDAB2IP on Prostate Cancer and its Disease Correlation

    DTIC Science & Technology

    2007-02-01

    hDAB2, a candidate tumor suppressor gene involved in the devel- opment of gestational trophoblastic diseases . Oncogene 17, 419–424. GLANZER, J.G., LIAO...hDAB2IP on Prostate Cancer and its Disease Correlation PRINCIPAL INVESTIGATOR: Jer-Tsong Hsieh, Ph.D. CONTRACTING...SUBTITLE Analysis of Morphogenic Effect of hDAB2IP on Prostate Cancer and its Disease 5a. CONTRACT NUMBER Correlation 5b. GRANT NUMBER W81XWH

  15. 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.

  16. Effects of interferons and double-stranded RNA on human prostate cancer cell apoptosis

    PubMed Central

    Tan, Haiyan; Zeng, Chun; Xie, Junbo; Alghamdi, Norah J.; Song, Ya; Zhang, Hongbing; Zhou, Aimin; Jin, Di

    2015-01-01

    Prostate cancer is the second most commonly diagnosed cancer among men in the United States. Prostate cancer therapy is severely hampered by lack of response and development of resistance to conventional chemotherapeutic drugs in patients. Therefore, the development and discovery of new drugs have become an urgent clinical need. Interferons (IFNs), a family of pleiotropic cytokines, exert antitumor activities due to their anti-proliferative, immunomodulatory and proapoptotic functions. Here, we report that pretreatment of prostate cancer PC-3 cells with IFNs sensitized these cells to double-stranded RNAs (dsRNAs)-induced apoptosis. The enhancement effect of IFN treatment was dependent on IFN subtypes, in particular, IFN γ. In comparison with IFN α or β, IFN γ treatment remarkably augmented apoptosis in PC-3 cells induced with polyinosinic:polycytidylic acid (poly I:C), a synthesized form of dsRNA. We demonstrated that IFN-signaling was necessary for these effects by using mutant cell lines. Transfection of 2–5A, the activator of RNase L, or silencing of dsRNA-dependent protein kinase R (PKR) by siRNA did not have any significant impact on this event, suggesting that neither RNase L nor PKR was involved in poly I:C/IFN γ-induced apoptosis in the cells. Further investigation of the apoptotic pathway revealed that Bak, a pro-apoptotic member of the Bcl-2family, was synergistically up-regulated by IFN γ and poly I:C, whereas other members of the family were not affected. Knocking down of Bak demonstrated its contribution to poly I:C/IFN γ-induced apoptosis in the cells. We believeour findings will precipitate the design of novel therapeutic strategies for prostate cancer. PMID:26452032

  17. Effect of AQP9 Expression in Androgen-Independent Prostate Cancer Cell PC3

    PubMed Central

    Chen, Qiwei; Zhu, Liang; Zheng, Bo; Wang, Jinliang; Song, Xishuang; Zheng, Wei; Wang, Lina; Yang, Deyong; Wang, Jianbo

    2016-01-01

    It is known that aquaporin 9 (AQP9) in the prostate was strictly upregulated by androgen and may represent a novel therapeutic target for several cancers, but whether AQP9 plays a role in the regulation of androgen-independent prostate cancer still remains unclear. In the present study, AQP9 was determined in prostate cancer and adjacent cancer tissues; AQP9-siRNA was applied to silencing AQP9 in androgen-independent prostate cancer cell PC3 cell line. Western blot and flow cytometry analysis were employed to detect changes in related-function of control and AQP9-siRNA groups. The results showed that AQP9 is significantly induced in cancer tissues than that in adjacent cancer tissues. Moreover, knockdown of AQP9 in PC3 androgen-independent prostate cancer cell prostate cancer cells increased inhibition rates of proliferation. In addition, knockdown of AQP9 resulted in a significant decrease in the expression of the Bcl-2 and with a notable increase in the expression of Bax and cleaved caspase 3, indicated that AQP9 knockdown promoted apoptosis in prostate cancer cells. From wound healing assay and matrigel invasion, we suggested that AQP9 expression affects the motility and invasiveness of prostate cancer cells. Moreover, In order to explore the pathway may be involved in AQP9-mediated motility and invasion of prostate cancer cells, the phosphorylation of ERK1/2 was significant suppressed in AQP9 siRNA-transfected cells compared with that in control cells, suggesting that AQP9 is involved in the activation of the ERK pathway in androgen-independent prostate cancer cells. PMID:27187384

  18. TGF-β Effects on Prostate Cancer Cell Migration and Invasion Require FosB

    PubMed Central

    Barrett, Cachétne S.X.; Millena, Ana C.; Khan, Shafiq A.

    2017-01-01

    BACKGROUND Activator Protein-1 (AP-1) family (cJun, JunB, JunD, cFos, FosB, Fra1, and Fra2) plays a central role in the transcriptional regulation of many genes that are associated with cell proliferation, differentiation, migration, metastasis, and survival. Many oncogenic signaling pathways converge at the AP-1 transcription complex. Transforming growth factor beta (TGF-β) is a multifunctional regulatory cytokine that regulates many aspects of cellular function, including cellular proliferation, differentiation, migration, apoptosis, adhesion, angiogenesis, immune surveillance, and survival. METHODS This study investigated, the role of FOS proteins in TGF-β signaling in prostate cancer cell proliferation, migration, and invasion. Steady state expression levels of FOS mRNA and proteins were determined using RT-PCR and western blotting analyses. DU145 and PC3 prostate cancer cells were exposed to TGF-β1 at varying time and dosage, RT-PCR, western blot, and immunofluorescence analyses were used to determine TGF-β1 effect on FOS mRNA and protein expression levels as well as FosB subcellular localization. Transient silencing of FosB protein was used to determine its role in cell proliferation, migration, and invasion. RESULTS Our data show that FOS mRNA and proteins were differentially expressed in human prostate epithelial (RWPE-1) and prostate cancer cell lines (LNCaP, DU145, and PC3). TGF-β1 induced the expression of FosB at both the mRNA and protein levels in DU145 and PC3 cells, whereas cFos and Fra1 were unaffected. Immunofluorescence analysis showed an increase in the accumulation of FosB protein in the nucleus of PC3 cells after treatment with exogenous TGF-β1. Selective knockdown of endogenous FosB by specific siRNA did not have any effect on cell proliferation in PC3 and DU145 cells. However, basal and TGF-β1- and EGF-induced cell migration was significantly reduced in DU145 and PC3 cells lacking endogenous FosB. TGF-β1- and EGF-induced cell invasion

  19. The novel Akt inhibitor Palomid 529 (P529) enhances the effect of radiotherapy in prostate cancer.

    PubMed

    Diaz, R; Nguewa, P A; Diaz-Gonzalez, J A; Hamel, E; Gonzalez-Moreno, O; Catena, R; Serrano, D; Redrado, M; Sherris, D; Calvo, A

    2009-03-24

    Radiotherapy (RT) is a common treatment for localised prostate cancer, but can cause important side effects. The therapeutic efficacy of RT can be enhanced by pharmacological compounds that target specific pathways involved in cell survival. This would elicit a similar therapeutic response using lower doses of RT and, in turn, reducing side effects. This study describes the antitumour activity of the novel Akt inhibitor 8-(1-Hydroxy-ethyl)-2-methoxy-3-(4-methoxy-benzyloxy)-benzo[c]chromen-6-one (Palomid 529 or P529) as well as its ability to decrease radiation-activated phospho-Akt (p-Akt) signalling in a prostate cancer model. P529 showed a potent antiproliferative activity in the NCI-60 cell lines panel, with growth inhibitory 50 (GI50) <35 microM. In addition, P529 significantly enhanced the antiproliferative effect of radiation in prostate cancer cells (PC-3). Analysis of signalling pathways targeted by P529 exhibited a decrease in p-Akt, VEGF, MMP-2, MMP-9, and Id-1 levels after radiation treatment. Moreover, the Bcl-2/Bax ratio was also reduced. Treatment of PC-3 tumour-bearing mice with 20 mg kg(-1) P529 or 6 Gy radiation dose decreased tumour size by 42.9 and 53%, respectively. Combination of both treatments resulted in 77.4% tumour shrinkage. Decreased tumour growth was due to reduced proliferation and increased apoptosis (as assessed by PCNA and caspase-3 immunostaining). Our results show the antitumour efficacy of P529 alone, and as a radiosensitiser, and suggest that this compound could be used in the future to treat human prostate cancer.

  20. The novel Akt inhibitor Palomid 529 (P529) enhances the effect of radiotherapy in prostate cancer

    PubMed Central

    Diaz, R; Nguewa, P A; Diaz-Gonzalez, J A; Hamel, E; Gonzalez-Moreno, O; Catena, R; Serrano, D; Redrado, M; Sherris, D; Calvo, A

    2009-01-01

    Radiotherapy (RT) is a common treatment for localised prostate cancer, but can cause important side effects. The therapeutic efficacy of RT can be enhanced by pharmacological compounds that target specific pathways involved in cell survival. This would elicit a similar therapeutic response using lower doses of RT and, in turn, reducing side effects. This study describes the antitumour activity of the novel Akt inhibitor 8-(1-Hydroxy-ethyl)-2-methoxy-3-(4-methoxy-benzyloxy)-benzo[c]chromen-6-one (Palomid 529 or P529) as well as its ability to decrease radiation-activated phospho-Akt (p-Akt) signalling in a prostate cancer model. P529 showed a potent antiproliferative activity in the NCI-60 cell lines panel, with growth inhibitory 50 (GI50) <35 μM. In addition, P529 significantly enhanced the antiproliferative effect of radiation in prostate cancer cells (PC-3). Analysis of signalling pathways targeted by P529 exhibited a decrease in p-Akt, VEGF, MMP-2, MMP-9, and Id-1 levels after radiation treatment. Moreover, the Bcl-2/Bax ratio was also reduced. Treatment of PC-3 tumour-bearing mice with 20 mg kg−1 P529 or 6 Gy radiation dose decreased tumour size by 42.9 and 53%, respectively. Combination of both treatments resulted in 77.4% tumour shrinkage. Decreased tumour growth was due to reduced proliferation and increased apoptosis (as assessed by PCNA and caspase-3 immunostaining). Our results show the antitumour efficacy of P529 alone, and as a radiosensitiser, and suggest that this compound could be used in the future to treat human prostate cancer. PMID:19240717

  1. Tocopherols and saponins derived from Argania spinosa exert, an antiproliferative effect on human prostate cancer.

    PubMed

    Drissi, A; Bennani, H; Giton, F; Charrouf, Z; Fiet, J; Adlouni, A

    2006-10-01

    The aim of our study is to evaluate the antiproliferative effect of tocopherols obtained from alimentary virgin argan oil extracted from the endemic argan tree of Morocco and of saponins extracted from argan press cake on three human prostatic cell lines (DU145, LNCaP, and PC3). The results were compared to 2-methoxyestradiol as antiproliferative drug candidates. Cytotoxicity and antiproliferative effects were investigated after cells' treatment with tocopherols and saponins compared to 2-Methoxyoestradiol as the positive control. Tocopherols and saponins extracted from argan tree and 2-methoxyestradiol exhibit a dose-response cytotoxic effect and an antiproliferative action on the tested cell lines. The best antiproliferative effect of tocopherols is obtained with DU145 and LNCaP cell lines (28 microg/ml and 32 microg/ml, respectively, as GI50). The saponins fraction displayed the best antiproliferative effect on the PC3 cell line with 18 microg/ml as GI50. Our results confirm the antiproliferative effect of 2-methoxyestradiol and show for the first time the antiproliferative effect of tocopherols and saponins extracted from the argan tree on hormone-dependent and hormone-independent prostate cancer cell lines. These data suggest that argan oil is of potential interest in developing new strategies for prostate cancer prevention.

  2. 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.

  3. Biological Effects of TMPRSS2/ERG Fusion Isoforms in Human Prostate Cancer

    DTIC Science & Technology

    2009-02-01

    40–5. 11. Lapointe J, Kim YH, Miller MA, et al. A variant TMPRSS2 isoform and ERG fusion product in prostate cancer with implications for molecular ... diagnosis . Mod Pathol 2007;20:467–73. 12. Demichelis F, Fall K, Perner S, et al. TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a

  4. 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

  5. Prostate cancer in native Japanese and Japanese-American men: effects of dietary differences on prostatic tissue.

    PubMed

    Marks, Leonard S; Kojima, Munekado; Demarzo, Angelo; Heber, David; Bostwick, David G; Qian, Junqi; Dorey, Frederick J; Veltri, Robert W; Mohler, James L; Partin, Alan W

    2004-10-01

    To investigate the relationship between diet and prostate cancer (CaP) among native Japanese (NJ) and second-generation or third-generation Japanese-American (J-A) men--focusing on the effects of animal fat and soy on prostatic tissues. The subjects were 50 Japanese men undergoing radical prostatectomy, 25 NJ living in Nagoya, Japan and 25 U.S.-born J-A men, living in Los Angeles, California. A priori, the NJ men were believed to be a low-fat, high-soy group and the J-A men, a high-fat, low-soy group. The studies included postoperative measurements of diet (Block questionnaire), body fat (bioimpedance), blood, urine, and prostatic biomarkers in malignant and adjacent normal tissue, using a tissue microarray made from the original paraffin blocks. The NJ and J-A men were similar in age (65 to 70 years old; P <0.05), prostate-specific antigen level (7.1 to 8.6 ng/mL), prostate volume (35 to 38 cm3), and Gleason score (5.6 to 6.6), but their body composition differed. J-A men had more body fat (24% versus 19%), higher serum triglyceride levels (245 versus 106 mg/dL), lower estradiol levels (27 versus 31 ng/mL), and much lower urinary soy-metabolite levels (1:3) than NJ men (P <0.02). In both NJ and J-A groups, expression of numerous tissue biomarkers separated normal from CaP tissue, including markers for apoptosis (Bcl-2, caspase-3), growth factor receptors (epidermal growth factor receptor), racemase, 5-lipoxygenase, kinase inhibition (p27), and cell proliferation (Ki-67; all P <0.02). Furthermore, within both normal and CaP tissues, caspase-3 and 5-lipoxygenase were expressed more in NJ than in J-A men (P <0.01). Nuclear morphometry showed that the chromatin in each of the four groups (normal versus CaP, NJ versus J-A) was different (area under the curve 85% to 94%, P <0.01), despite fundamental genetic homogeneity. NJ and J-A men, products of similar genetics but differing environments, were shown to have differences in body composition that could influence Ca

  6. Effectiveness of Androgen-Deprivation Therapy and Radiotherapy for Older Men With Locally Advanced Prostate Cancer

    PubMed Central

    Bekelman, Justin E.; Mitra, Nandita; Handorf, Elizabeth A.; Uzzo, Robert G.; Hahn, Stephen A.; Polsky, Daniel; Armstrong, Katrina

    2015-01-01

    Purpose We examined whether the survival advantage of androgen-deprivation therapy with radiotherapy (ADT plus RT) relative to ADT alone for men with locally advanced prostate cancer reported in two randomized trials holds in real-world clinical practice and extended the evidence to patients poorly represented in the trials. Methods We conducted nonrandomized effectiveness studies of ADT plus RT versus ADT in three groups of patients diagnosed between 1995 and 2007 and observed through 2009 in the SEER-Medicare data set: (1) the randomized clinical trial (RCT) cohort, which included men age 65 to 75 years and was most consistent with participants in the randomized trials; (2) the elderly cohort, which included men age > 75 years with locally advanced prostate cancer; and (3) the screen-detected cohort, which included men age ≥ 65 years with screen-detected high-risk prostate cancer. We evaluated cause-specific and all-cause mortality using propensity score, instrumental variable (IV), and sensitivity analyses. Results In the RCT cohort, ADT plus RT was associated with reduced cause-specific and all-cause mortality relative to ADT alone (cause-specific propensity score–adjusted hazard ratio [HR], 0.43; 95% CI, 0.37 to 0.49; all-cause propensity score–adjusted HR, 0.63; 95% CI, 0.59 to 0.67). Effectiveness estimates for the RCT cohort were not significantly different from those from randomized trials (P > .1). In the elderly and screen-detected cohorts, ADT plus RT was also associated with reduced cause-specific and all-cause mortality. IV analyses produced estimates similar to those from propensity score–adjusted methods. Conclusion Older men with locally advanced or screen-detected high-risk prostate cancer who receive ADT alone risk decrements in cause-specific and overall survival. PMID:25559808

  7. Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells

    PubMed Central

    Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M.; Vadgama, Jaydutt V.

    2014-01-01

    Scope We investigated whether a combination of two promising chemopreventive agents arctigenin and quercetin increases the anti-carcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Methods and results Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of arctigenin and quercetin alone or in combination for 48h. The anti-proliferative activity of arctigenin was 10-20 fold stronger than quercetin in both cell lines. Their combination synergistically enhanced the anti-proliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arctigenin demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. Conclusion The combination of arctigenin and quercetin, that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. PMID:25380086

  8. Arctigenin in combination with quercetin synergistically enhances the antiproliferative effect in prostate cancer cells.

    PubMed

    Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M; Vadgama, Jaydutt V

    2015-02-01

    We investigated whether a combination of two promising chemopreventive agents arctigenin (Arc) and quercetin (Q) increases the anticarcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of Arc and Q alone or in combination for 48 h. The antiproliferative activity of Arc was 10- to 20-fold stronger than Q in both cell lines. Their combination synergistically enhanced the antiproliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arc demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. The combination of Arc and Q that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. 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.

  10. Mouse Models of Prostate Cancer

    PubMed Central

    Valkenburg, Kenneth C.; Williams, Bart O.

    2011-01-01

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

  11. Obesity, serum prostate specific antigen and prostate size: implications for prostate cancer detection.

    PubMed

    Freedland, Stephen J; Platz, Elizabeth A; Presti, Joseph C; Aronson, William J; Amling, Christopher L; Kane, Christopher J; Terris, Martha K

    2006-02-01

    Obesity has been associated with lower serum testosterone, theoretically resulting in decreased PSA production. Obesity has also been associated with prostatic enlargement, making the detection of existent cancer more difficult. Together these findings would result in an apparent protective effect of obesity on prostate cancer risk due to technical detection issues unrelated to cancer biology. We examined the association between BMI, and PSA and prostate weight in a cohort of men undergoing RP. We evaluated the association of BMI with prostate weight and PSA using linear regression, adjusting for patient age at RP, year of RP, race, and pathological stage and grade in 1,414 men treated with RP between 1988 and 2004 at the 5 equal access medical centers that comprise the Shared Equal Access Regional Cancer Hospital Database. On multivariate analysis increasing BMI was associated with increasing prostate weight but only in men younger than 63 years and not in men 63 years or older (p-trend <0.001 and 0.44, respectively). In men younger than 63 years mean multivariate adjusted prostate weight +/- SE in those with a BMI of less than 25 vs 30 to 34.9 kg/m was 33.8 +/- 1.4 vs 41.4 +/- 1.6 gm. There was no significant association between BMI and preoperative PSA (p-trend = 0.70). In a cohort of men undergoing RP obesity was associated with larger prostate size but only in younger men. There was no association between BMI and PSA. Assuming equal PSA, the degree of prostatic enlargement observed in younger obese men in this study would be expected to result in a modest decrease in the odds of detecting prostate cancer in a contemporary series of PSA screened men due to the decreased sensitivity of cancer detection related to larger prostate size. Obesity may appear protective for prostate cancer in younger men due to technical issues unrelated to cancer biology.

  12. Treatment options for localized prostate cancer

    PubMed Central

    Keyes, Mira; Crook, Juanita; Morton, Gerard; Vigneault, Eric; Usmani, Nawaid; Morris, W. James

    2013-01-01

    Abstract Objective To describe treatment options for clinically localized prostate cancer: radical prostatectomy, prostate brachytherapy, external beam radiation, and active surveillance. Quality of evidence Prostate-specific antigen (PSA) outcomes presented are from non-randomized, cohort, and other comparisons trials (level II evidence). We describe PSA outcomes from Canadian centres when they are available. One small randomized controlled trial (level I evidence) in localized prostate cancer is available to compare radical prostatectomy with brachytherapy. Main message Treatment choice in prostate cancer is based on initial PSA level, clinical stage of disease, and Gleason score, together with baseline urinary function, comorbidities, and patient age. In this article, we describe patients’ eligibility for and the common side effects of all treatment options. Prostate brachytherapy and active surveillance have evolved as new standard treatments of localized prostate cancer. We give a brief overview of the brachytherapy procedure, side effects, and PSA outcomes across Canada, as well as active surveillance guidelines. Conclusion Prostate cancer treatment requires a multidisciplinary approach, with input from both urology and radiation oncology. Input from family physicians is often as important in helping guide patients through the treatment decision process. PMID:24336537

  13. Optimization of Invasion-Specific Effects of Betulin Derivatives on Prostate Cancer Cells through Lead Development.

    PubMed

    Härmä, Ville; Haavikko, Raisa; Virtanen, Johannes; Ahonen, Ilmari; Schukov, Hannu-Pekka; Alakurtti, Sami; Purev, Enkhee; Rischer, Heiko; Yli-Kauhaluoma, Jari; Moreira, Vânia M; Nees, Matthias; Oksman-Caldentey, Kirsi-Marja

    2015-01-01

    The anti-invasive and anti-proliferative effects of betulins and abietane derivatives was systematically tested using an organotypic model system of advanced, castration-resistant prostate cancers. A preliminary screen of the initial set of 93 compounds was performed in two-dimensional (2D) growth conditions using non-transformed prostate epithelial cells (EP156T), an androgen-sensitive prostate cancer cell line (LNCaP), and the castration-resistant, highly invasive cell line PC-3. The 25 most promising compounds were all betulin derivatives. These were selected for a focused secondary screen in three-dimensional (3D) growth conditions, with the goal to identify the most effective and specific anti-invasive compounds. Additional sensitivity and cytotoxicity tests were then performed using an extended cell line panel. The effects of these compounds on cell cycle progression, mitosis, proliferation and unspecific cytotoxicity, versus their ability to specifically interfere with cell motility and tumor cell invasion was addressed. To identify potential mechanisms of action and likely compound targets, multiplex profiling of compound effects on a panel of 43 human protein kinases was performed. These target de-convolution studies, combined with the phenotypic analyses of multicellular organoids in 3D models, revealed specific inhibition of AKT signaling linked to effects on the organization of the actin cytoskeleton as the most likely driver of altered cell morphology and motility.

  14. Biomarkers in Prostate Cancer Epidemiology

    PubMed Central

    Verma, Mukesh; Patel, Payal; Verma, Mudit

    2011-01-01

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

  15. Optimising the Diagnosis of Prostate Cancer in the Era of Multiparametric Magnetic Resonance Imaging: A Cost-effectiveness Analysis Based on the Prostate MR Imaging Study (PROMIS).

    PubMed

    Faria, Rita; Soares, Marta O; Spackman, Eldon; Ahmed, Hashim U; Brown, Louise C; Kaplan, Richard; Emberton, Mark; Sculpher, Mark J

    2017-09-18

    The current recommendation of using transrectal ultrasound-guided biopsy (TRUSB) to diagnose prostate cancer misses clinically significant (CS) cancers. More sensitive biopsies (eg, template prostate mapping biopsy [TPMB]) are too resource intensive for routine use, and there is little evidence on multiparametric magnetic resonance imaging (MPMRI). To identify the most effective and cost-effective way of using these tests to detect CS prostate cancer. Cost-effectiveness modelling of health outcomes and costs of men referred to secondary care with a suspicion of prostate cancer prior to any biopsy in the UK National Health Service using information from the diagnostic Prostate MR Imaging Study (PROMIS). Combinations of MPMRI, TRUSB, and TPMB, using different definitions and diagnostic cut-offs for CS cancer. Strategies that detect the most CS cancers given testing costs, and incremental cost-effectiveness ratios (ICERs) in quality-adjusted life years (QALYs) given long-term costs. The use of MPMRI first and then up to two MRI-targeted TRUSBs detects more CS cancers per pound spent than a strategy using TRUSB first (sensitivity = 0.95 [95% confidence interval {CI} 0.92-0.98] vs 0.91 [95% CI 0.86-0.94]) and is cost effective (ICER = £7,076 [€8350/QALY gained]). The limitations stem from the evidence base in the accuracy of MRI-targeted biopsy and the long-term outcomes of men with CS prostate cancer. An MPMRI-first strategy is effective and cost effective for the diagnosis of CS prostate cancer. These findings are sensitive to the test costs, sensitivity of MRI-targeted TRUSB, and long-term outcomes of men with cancer, which warrant more empirical research. This analysis can inform the development of clinical guidelines. We found that, under certain assumptions, the use of multiparametric magnetic resonance imaging first and then up to two transrectal ultrasound-guided biopsy is better than the current clinical standard and is good value for money. Copyright

  16. Effect of caffeine on exercise capacity and function in prostate cancer survivors.

    PubMed

    Cornish, Rahchell S; Bolam, Kate A; Skinner, Tina L

    2015-03-01

    This study aimed to examine the acute effect of caffeine on exercise capacity, exercise-related fatigue, and functional performance in prostate cancer survivors. In this randomized, placebo-controlled, double-blind crossover study, 30 prostate cancer survivors (age, 70.3 ± 7.7 yr; body mass, 80.5 ± 13.0 kg; mean ± SD) consumed 6.04 ± 0.16 mg·kg(-1) of anhydrous caffeine or a placebo 1 h before completing a battery of exercise capacity and functional performance tests. Testing sessions were separated by 3-4 wk. Immediate fatigue and perceived exertion were measured directly pre- and postexercise at both testing sessions. Caffeine increased exercise capacity by 7.93 s (+3.0%; P = 0.010); however, postexercise fatigue and perception of exertion were comparable with the placebo session (P = 0.632 and P = 0.902, respectively). Increases in isometric grip strength trended toward significance in both dominant (+2.9%; P = 0.053) and nondominant (+2.1%; P = 0.061) hands in the caffeine trial compared with placebo. Caffeine ingestion did not result in improvements in performance for any of the remaining functional measures, including the timed up-and-go test, repeated chair stands, 6-m fast walk, and 6-m backward tandem walk. Systolic blood pressure and HR were significantly increased (P = 0.006 and P = 0.040, respectively) upon completion of the testing battery when compared with placebo. Consumption of caffeine 1 h before exercise induced improvements in exercise capacity and muscular strength in prostate cancer survivors. However, there was no change in exercise-related fatigue when compared with placebo despite reduction in timed performance of the 400-m walk. Caffeine seems to enhance exercise tolerance through improved performance with no subsequent increase in fatigue or perception of exertion and may be an appropriate strategy to promote exercise participation in prostate cancer survivors.

  17. 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].

  18. Androgen receptor in prostate cancer.

    PubMed

    Heinlein, Cynthia A; Chang, Chawnshang

    2004-04-01

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

  19. Effect of triptorelin on lower urinary tract symptoms in Australian prostate cancer patients

    PubMed Central

    Woo, Henry H; Murphy, Declan G; Testa, Gerard M; Grummet, Jeremy P; Chong, Michael; Stork, Andrew P

    2017-01-01

    Purpose Prostate cancer is often comorbidly associated with lower urinary tract symptoms (LUTS), but few studies have assessed the effects of androgen deprivation therapy on LUTS in this patient group. Patients and methods We conducted a prospective, noninterventional, multicenter, observational study to assess the effectiveness of triptorelin (11.25 mg every 12 weeks) over 48 weeks in men presenting with local stage T3/4 prostate cancer and moderate to severe LUTS (International Prostate Symptom Score [IPSS] >7) in a routine practice setting in Australia. Results Of the 44 men who enrolled, effectiveness data were available for 39 men. By the end of the study, 30% of men no longer met the IPSS criteria for moderate to severe LUTS. The proportion of patients with moderate to severe LUTS was 69.6% (16/23) at week 48 and 76.9% (30/39) at the last available visit (coprimary outcomes). An IPSS reduction of ≥3 from week 0 was observed in 47% of men at week 4, 56% at week 24, 61% (14/23) at week 48, and 61.5% (24/39) at the last available visit. Quality of life was rated as mostly satisfied-to-delighted by 39.5% of patients at week 0, 53.9% at week 24, and 77.3% at week 48. Triptorelin was well tolerated with 8 treatment-related adverse events reported, half of which were hot flushes; 5 patients discontinued due to the reported treatment-related adverse events. Conclusion This observational study suggests that triptorelin improves moderate to severe LUTS in prostate cancer patients in a routine clinical practice setting. PMID:28261572

  20. Prostate Cancer Aggressiveness Gene in Hereditary Prostate Cancer

    DTIC Science & Technology

    2007-03-01

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

  1. Targeting Prostate Cancer Metastasis

    DTIC Science & Technology

    2015-09-01

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

  2. Unique Approaches to Androgen Effects on Prostate Cancer

    DTIC Science & Technology

    2007-02-01

    Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a...SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b. ABSTRACT U...hormone-binding globulin (SHBG) not only binds testosterone (T) and other androgens in plasma, but is part of a prostatic androgen signal transduction

  3. Accumulation of Palmitoylcarnitine and Its Effect on Pro-Inflammatory Pathways and Calcium Influx in Prostate Cancer.

    PubMed

    Al-Bakheit, Ala'a; Traka, Maria; Saha, Shikha; Mithen, Richard; Melchini, Antonietta

    2016-10-01

    Acylcarnitines are intermediates of fatty acid oxidation and accumulate as a consequence of the metabolic dysfunction resulting from the insufficient integration between β-oxidation and the tricarboxylic acid (TCA) cycle. The aim of this study was to investigate whether acylcarnitines accumulate in prostate cancer tissue, and whether their biological actions could be similar to those of dihydrotestosterone (DHT), a structurally related compound associated with cancer development. Levels of palmitoylcarnitine (palcar), a C16:00 acylcarnitine, were measured in prostate tissue using LC-MS/MS. The effect of palcar on inflammatory cytokines and calcium (Ca(2+) ) influx was investigated in in vitro models of prostate cancer. We observed a significantly higher level of palcar in prostate cancerous tissue compared to benign tissue. High levels of palcar have been associated with increased gene expression and secretion of the pro-inflammatory cytokine IL-6 in cancerous PC3 cells, compared to normal PNT1A cells. Furthermore, we found that high levels of palcar induced a rapid Ca(2+) influx in PC3 cells, but not in DU145, BPH-1, or PNT1A cells. This pattern of Ca(2+) influx was also observed in response to DHT. Through the use of whole genome arrays we demonstrated that PNT1A cells exposed to palcar or DHT have a similar biological response. This study suggests that palcar might act as a potential mediator for prostate cancer progression through its effect on (i) pro-inflammatory pathways, (ii) Ca(2+) influx, and (iii) DHT-like effects. Further studies need to be undertaken to explore whether this class of compounds has different biological functions at physiological and pathological levels. Prostate 76:1326-1337, 2016. © 2016 The Authors. The Prostate published by Wiley Periodicals, Inc. © 2016 The Authors. The Prostate published by Wiley Periodicals, Inc.

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

    PubMed

    Iversen, Peter; Roder, Martin Andreas

    2008-03-01

    The Early Prostate Cancer program is investigating the addition of bicalutamide 150 mg to standard care for localized or locally advanced, nonmetastatic prostate cancer. The third program analysis, at 7.4 years' median follow-up, has shown that bicalutamide 150 mg does not benefit patients with localized disease, but does confer significant progression-free survival benefits in patients with locally advanced disease, irrespective of standard care received. In patients receiving radiotherapy for locally advanced disease, bicalutamide 150 mg significantly reduced the risk of death by 35%; the magnitude of this benefit compares favorably with that of adjuvant luteinizing hormone-releasing hormone agonist therapy in a similar population. Bicalutamide 150 mg represents an alternative to castration for patients with locally advanced disease who wish to avoid the side effects associated with castration.

  5. Understanding Fragmentation of Prostate Cancer Survivorship Care

    PubMed Central

    Skolarus, Ted A.; Zhang, Yun; Hollenbeck, Brent K.

    2016-01-01

    BACKGROUND Cancer survivors are particularly prone to the effects of a fragmented health care delivery system. The implications of fragmented cancer care across providers likely include greater spending and worse quality of care. For this reason, the authors measured relations between increasing fragmentation of cancer care, expenditures, and quality of care among prostate cancer survivors. METHODS A total of 67,736 patients diagnosed with prostate cancer between 1992 and 2005 were identified using Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Using the Herfindahl-Hirschman Index and a measure of the average number of prostate cancer providers over time, patients were sorted into 3 fragmentation groups (low, intermediate, and high). The authors then examined annual per capita survivorship expenditures and a measure of quality (ie, repetitive prostate-specific antigen [PSA] testing within 30 days) according to their fragmentation exposure using multinomial logistic regression. RESULTS Patients with highly fragmented cancer care tended to be younger, white, and of higher socioeconomic status (all P < .001). Prostate cancer survivorship interventions were most common among patients with the highest fragmentation of care across providers (P < .001). After adjustment for clinical characteristics and prostate cancer survivorship interventions, higher degrees of fragmentation continued to be associated with repetitive PSA testing (13.6% for high vs 7.0% for low fragmentation; P < .001) and greater spending, particularly among patients not treated with androgen deprivation therapy. CONCLUSIONS Fragmented prostate cancer survivorship care is expensive and associated with potentially unnecessary services. Efforts to improve care coordination via current policy initiatives, electronic medical records, and the implementation of cancer survivorship tools may help to decrease fragmentation of care and mitigate downstream consequences for prostate cancer

  6. Metformin enhances the antiproliferative and apoptotic effect of bicalutamide in prostate cancer.

    PubMed

    Colquhoun, A J; Venier, N A; Vandersluis, A D; Besla, R; Sugar, L M; Kiss, A; Fleshner, N E; Pollak, M; Klotz, L H; Venkateswaran, V

    2012-12-01

    Prostate cancer incidence and mortality vary dramatically by geographical location. Both are higher in developed countries. Some attribute this to westernized lifestyles of high-energy diets and limited physical activity with consequent obesity. Obesity and obesity-related diseases like diabetes cause hyperinsulinaemia, which upregulates pro-survival cell signalling. Previous work revealed diet-induced hyperinsulinaemia enhances prostate cancer xenograft growth in vivo. Metformin, an antidiabetic medication, reduces hyperinsulinaemia and also exhibits antineoplastic properties. Herein, we assess the potential additive benefit of combining bicalutamide antiandrogen therapy with metformin, in vitro and in vivo. Using clonogenic assays, we assessed the effect of bicalutamide and/or metformin on clonogenicity in prostate cancer cell lines. Western blot and cell cycle analyses were used to elucidate mechanisms of interaction between the drugs in androgen receptor (AR)-positive (LNCaP) and AR-negative (PC3) cell lines. The combination treatment regimen was assessed in vivo using an LNCaP murine xenograft model. Micromolar bicalutamide or millimolar metformin caused a significant dose-dependent reduction in clonogenicity (P<0.001). Combination treatment further significantly reduced clonogenicity (P<0.005) with greater effects in AR-positive cells. Western blot and cell cycle analyses suggested differing mechanisms of interaction in AR-positive and -negative cell lines. Following combination treatment, LNCaP cells exhibited an altered cell proliferation (decreased phospho mammalian target of rapamycin expression) and perturbed cell cycle kinetics (G1/S cell cycle arrest). PC3 cells showed evidence of enhanced apoptosis (increased Bcl-2-associated X protein and decreased total caspase 3 expression). Markedly diminished tumour growth occurred following combination treatment in vivo (P<0.001). Combining bicalutamide and metformin significantly reduces prostate cancer cell

  7. Development of a standardized and effect-optimized herbal extract of Wedelia chinensis for prostate cancer.

    PubMed

    Tsai, Chin-Hsien; Tzeng, Sheue-Fen; Hsieh, Shih-Chuan; Lin, Chih-Yu; Tsai, Chia-Jui; Chen, Yet-Ran; Yang, Yu-Chih; Chou, Ya-Wen; Lee, Ming-Ting; Hsiao, Pei-Wen

    2015-03-15

    Herbal medicine is a popular complementary or alternative treatment for prostate cancer. Wedelia chinensis has at least three active compounds, wedelolactone, luteolin, and apigenin synergistically inhibiting prostate cancer cell growth in vitro. Here, we report a systematic study to develop a standardized and effect-optimized herbal extract, designated as W. chinensis extract (WCE) to facilitate its future scientific validation and clinical use. Ethanolic extract of dried W. chinensis plant was further condensed, acid hydrolyzed, and enriched with preparative chromatography. The chemical compositions of multiple batches of the standardized preparation WCE were quantified by LC/MS/MS, and biological activities were analyzed by in vitro and in vivo assays. Furthermore, the pharmacokinetics of the holistic WCE were compared with the combination of the equivalent principal active compounds through oral administration. The results indicated that quantitative chemical assay and PSA (prostate-specific antigen)-reporter assay together are suitable to measure the quality and efficacy of a standardized Wedelia extract on a xenograft tumor model. The presence of minor concomitant compounds in WCE prolonged the systemic exposure to the active compounds, thus augmented the anti-tumor efficacy of WCE. In conclusion, a combination of LC/MS/MS and PSA reporter assay is suitable to qualify a standardized preparation of WCE. Furthermore, the pharmacokinetics and oral bioavailability of active compounds demonstrate that holistic WCE exerted additional pharmacological synergy beyond the multi-targeted therapeutic effects caused by more than one active compound. WCE merits a higher priority to be studied for use in prostate cancer treatment.

  8. The Anticancer Effect of Fucoidan in PC-3 Prostate Cancer Cells

    PubMed Central

    Boo, Hye-Jin; Hong, Ji-Young; Kim, Sang-Cheol; Kang, Jung-Il; Kim, Min-Kyoung; Kim, Eun-Ji; Hyun, Jin-Won; Koh, Young-Sang; Yoo, Eun-Sook; Kwon, Jung-Mi; Kang, Hee-Kyoung

    2013-01-01

    Fucoidan, a sulfated polysaccharide, has a variety of biological activities, such as anti-cancer, anti-angiogenic and anti-inflammatory. However, the mechanisms of action of fucoidan as an anti-cancer agent have not been fully elucidated. The present study examined the anti-cancer effect of fucoidan obtained from Undaria pinnatifida in PC-3 cells, human prostate cancer cells. Fucoidan induced the apoptosis of PC-3 cells by activating both intrinsic and extrinsic pathways. The induction of apoptosis was accompanied by the activation of extracellular signal-regulated kinase mitogen-activated protein kinase (ERK1/2 MAPK) and the inactivation of p38 MAPK and phosphatidylinositol 3-kinase (PI3K)/Akt. In addition, fucoidan also induced the up-regulation of p21Cip1/Waf and down-regulation of E2F-1 cell-cycle-related proteins. Furthermore, in the Wnt/β-catenin pathway, fucoidan activated GSK-3β that resulted in the decrease of β-catenin level, followed by the decrease of c-myc and cyclin D1 expressions, target genes of β-catenin in PC-3 cells. These results suggested that fucoidan treatment could induce intrinsic and extrinsic apoptosis pathways via the activation of ERK1/2 MAPK, the inactivation of p38 MAPK and PI3K/Akt signaling pathway, and the down-regulation of Wnt/β-catenin signaling pathway in PC-3 prostate cancer cells. These data support that fucoidan might have potential for the treatment of prostate cancer. PMID:23966032

  9. Endocrine disruptors and prostate cancer risk

    PubMed Central

    Prins, Gail S

    2010-01-01

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

  10. Dosimetric effects of endorectal balloons on intensity-modulated radiation therapy plans for prostate cancer

    NASA Astrophysics Data System (ADS)

    Kim, Jae-Sung; Chung, Jin-Beom; Kim, In-Ah; Eom, Keun-Yong

    2013-10-01

    We used an endorectal balloon (ERB) for prostate immobilization during intensity-modulated radiotherapy (IMRT) for prostate cancer treatment. To investigate the dosimetric effects of ERB-filling materials, we changed the ERB Hounsfield unit (HU) from 0 to 1000 HU in 200-HU intervals to simulate the various ERB fillings; 0 HU simulated a water-filled ERB, and 1000 HU simulated the densest material-filled ERB. Dosimetric data (coverage, homogeneity, conformity, maximal dose, and typical volume dose) for the tumor and the organs at risk (OARs) were evaluated in prostate IMRT treatment plans with 6-MV and 15-MV beams. The tumor coverage appeared to differ by approximately 1%, except for the clinical target volume (CTV) V100% and the planning target volume (PTV) V100%. The largest difference for the various ERB fillings was observed in the PTV V100%. In spite of increasing HU, the prostate IMRT plans at both energies had relatively low dosimetric effects on the PTV and the CTV. However, the maximal and the typical volume doses (D25%, D30%, and D50%) to the rectal wall and the bladder increased with increasing HU. For an air-filled ERB, the maximal doses to the rectal wall and the monitor units were lower than the corresponding values for the water-filled and the densest material-filled ERBs. An air-filled ERB spared the rectal wall because of its dosimetric effect. Thus, we conclude that the use of an air-filled ERB provides a dosimetric benefit to the rectal wall without a loss of target coverage and is an effective option for prostate IMRT treatment.

  11. Finasteride concentrations and prostate cancer risk: results from the Prostate Cancer Prevention Trial.

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  13. Methylselenium and Prostate Cancer Apoptosis

    DTIC Science & Technology

    2007-02-01

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

  14. Transrectal high-intensity focused ultrasound ablation of prostate cancer: effective treatment requiring accurate imaging.

    PubMed

    Rouvière, Olivier; Souchon, Rémi; Salomir, Rarès; Gelet, Albert; Chapelon, Jean-Yves; Lyonnet, Denis

    2007-09-01

    Transrectal HIFU ablation has become a reasonable option for the treatment of localized prostate cancer in non-surgical patients, with 5-year disease-free survival similar to that of radiation therapy. It is also a promising salvage therapy of local recurrence after radiation therapy. These favourable results are partly due to recent improvements in prostate cancer imaging. However, further improvements are needed in patient selection, pre-operative localization of the tumor foci, assessment of the volume treated and early detection of recurrence. A better knowledge of the factors influencing the HIFU-induced tissue destruction and a better pre-operative assessment of them by imaging techniques should improve treatment outcome. Whereas prostate HIFU ablation is currently performed under transrectal ultrasound guidance, MR guidance with real-time operative monitoring of temperature will be available in the near future. If this technique will give better targeting and more uniform tissue destruction, its cost-effectiveness will have to be carefully evaluated. Finally, a recently reported synergistic effect between HIFU ablation and chemotherapy opens possibilities for treatment in high-risk or clinically advanced tumors.

  15. 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

  16. Effect of Paget's disease of bone (osteitis deformans) on the progression of prostate cancer bone metastasis

    PubMed Central

    Tu, S-M; Som, A; Tu, B; Logothetis, C J; Lee, M-H; Yeung, S-CJ

    2012-01-01

    Background: Patients with prostate cancer tend to die from bone metastases. Until now, no evidence has shown that Paget's disease of bone (PDB) affects the progression of bone metastasis or overall survival of patients with prostate cancer. Methods: We searched our patient database for men who had presented with prostate cancer and PDB between June 1993 and March 2009, and identified best-matched control patients according to stage, grade, age, date of diagnosis, treatment, and race. Results: Among 1346 consecutive patients with prostate cancer diagnosed before 2008, 15 were confirmed to have comorbid PDB. Twenty-six more were identified from the institutional billing search. Including the 41 best-matched controls, our total study population was 82 patients. In the Kaplan–Meier analysis, we estimated median times from diagnosis of prostate cancer to bone metastasis to be 21.5 years for those with PDB and 9.4 years for those without PDB (P=0.044). Median overall survival times were 11.8 and 9.2 years for the two groups, respectively (P=0.008). Conclusion: For the first time, we have obtained evidence that patients with prostate cancer and PDB have delayed time to bone metastases and improved overall survival than do patients with prostate cancer alone. PMID:22805323

  17. 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

  18. Effect of metabolic syndrome and its components on prostate cancer risk: meta-analysis.

    PubMed

    Esposito, K; Chiodini, P; Capuano, A; Bellastella, G; Maiorino, M I; Parretta, E; Lenzi, A; Giugliano, D

    2013-02-01

    Literature data examining the role of metabolic syndrome and its components in prostate cancer risk are limited and contradictory. We did a meta-analysis of studies that evaluated the association between metabolic syndrome, its components, and risk of prostate cancer. We conducted an electronic search for articles published through September 2012 without restrictions. Every included study was to report risk estimates with 95% confidence intervals for the association between metabolic syndrome and prostate cancer. The final number of papers included in the meta-analysis was 14, all published in English, with 4728 prostate cancer cases. Metabolic syndrome was associated with a 12% increase in prostate cancer risk (p=0.231), that was lower in cohort studies (7 studies, RR=1.04, p=0.791) than other studies (RR=1.23, p=0.125). The association was significant in the 8 European studies (RR=1.30, p=0.034), but not in the 4 U.S. or 2 Asiatic studies. The risk estimates of prostate cancer for higher values of body mass index, dysglycemia or dyslipidemia (high triglycerides, low HDL-cholesterol) were not significant; on the contrary, hypertension and waist circumference >102 cm were associated with a significant 15% (p=0.035) and 56% (p=0.007) greater risk of prostate cancer, respectively. Metabolic syndrome is weakly and non significantly associated with prostate cancer risk, but associations vary with geography. Among single components of the syndrome, hypertension and higher waist circumference are significantly associated with increased risk of prostate cancer.

  19. 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...

  20. 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...

  1. Molecular Imaging of Prostate Cancer

    PubMed Central

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

    2016-01-01

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

  2. General Information about Prostate Cancer

    MedlinePlus

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

  3. Maximizing resources in the local treatment of prostate cancer: A summary of cost-effectiveness studies.

    PubMed

    Muralidhar, Vinayak; Nguyen, Paul L

    2017-02-01

    Prostate cancer is a common diagnosis with several treatment options for the newly diagnosed patient, including radiation, surgery, active surveillance, and watchful waiting. Although tailoring of treatment to individual patient needs is an important goal, the recent passage of the Affordable Care Act has placed renewed interest in cost containment and cost-effectiveness. We sought to conduct a literature review of recent US-based studies to analyze the cost-effectiveness of initial local treatments for localized prostate cancer. We conducted a systematic literature search through PubMed, the Cost-Effectiveness Analysis Registry, and manual cross-referencing of articles. We identified US-based studies with cost analyses starting in 2005 that studied the cost-effectiveness of initial local treatments for localized prostate cancer (surgery, radiation, or observation). There were eight studies that met our inclusion and exclusion criteria. Most studies took the cost perspective of Medicare, and two studies also considered the societal cost in terms of lost patient time. Most studies also used a Markov model with inputs based on the available literature for the effectiveness and toxicity of the different treatment options. The radiation-focused studies tended to find brachytherapy (BT) or stereotactic body radiation therapy (SBRT) to be more cost-effective than intensity-modulated radiation therapy or proton beam therapy. These findings were primarily based on the lower cost of SBRT or BT with roughly equal efficacy and toxicity. The two studies focused on surgery found surgery to be more cost effective than intensity-modulated radiation therapy, at least for low-risk disease, and one study found BT to be more cost-effective than surgery, and watchful waiting to be the most cost-effective option overall. Cost-effectiveness analysis is important because it helps patients, physicians, and policymakers make quantitatively-based decisions, which balance treatment efficacy

  4. Obesity, body composition, and prostate cancer.

    PubMed

    Fowke, Jay H; Motley, Saundra S; Concepcion, Raoul S; Penson, David F; Barocas, Daniel A

    2012-01-18

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

  5. 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.

  6. Urinary biomarkers for prostate cancer.

    PubMed

    Wei, John T

    2015-01-01

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

  7. 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 ...

  8. Prostate Cancer Mortality in Puerto Rican Men: The Effect of Body Habitus and Physical Activity

    DTIC Science & Technology

    2005-02-01

    92. 5. Chan, J. M., Stampfer , M. J., Ma, J., Gann, P. H., Gaziano, J. M., and Giovannucci, E. L. Dairy Products, Calcium, and Prostate Cancer Risk in...Risk of Prostate Cancer in US Physicians. Int J Epidemiol 2000;29:29-35. 43. Giovannucci, E, Leitzmann, M, Spiegelman, D, Rimm, EB, Colditz, GA, Stampfer ...Yan L, Leitzmann M, Wu K, Stampfer M, and Willett W. Body Mass Index and Risk of Prostate Cancer in U.S. Health Professionals. Journal of the

  9. 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.

  10. Biomarkers in localized prostate cancer

    PubMed Central

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

    2016-01-01

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

  11. Effects of long-term finasteride treatment on prostate cancer morphology and clinical outcome.

    PubMed

    Rubin, Mark A; Allory, Yves; Molinié, Vincent; Leroy, Xavier; Faucon, Hugo; Vacherot, Francis; Huang, Wei; Kuten, Adam; Salomon, Laurent; Rebillard, Xavier; Cussenot, Olivier; Abbou, Claude; de la Taille, Alexandre

    2005-11-01

    To examine the morphologic alterations of finasteride therapy on prostate cancer compared with no treatment or treatment with a luteinizing hormone-releasing hormone (LHRH) agonist and the clinical outcomes of patients treated with finasteride. The data of 56 patients with prostate cancer who had taken finasteride for at least 6 months were reviewed. A central pathology review was performed in a blinded manner comparing these patients with 56 matched controls and 44 patients who received a 3-month course of LHRH agonist before radical prostatectomy. The histologic hormonal treatment effects included apoptosis, vacuolated cytoplasm, pyknotic nuclei, and small irregular glands. An overall consensus was scored using a three-tiered system: no apparent effect (score = 0), suspicious for hormonal effect (score = 1), and highly suggestive of hormonal treatment (score = 2). A Gleason score was assigned to all prostatectomy specimens. The mean hormonal treatment score for the prostatectomy specimens was 0.4, 0.5, and 1.6 for the control, finasteride, and 3-month LHRH groups, respectively. Surprisingly, 20% of control patients had suspicious or highly suggestive hormonal effects and 26% of the finasteride-treated patients did so. For the LHRH-treated group, only 23% did not demonstrate classic features of hormonal treatment. Similar clinical outcomes were observed between the finasteride and control groups. No consistent hormonal therapy effects with finasteride treatment were observed compared with LHRH agonists. The hormonal effect was observed in the control group. Therefore, although other aspects of the Prostate Cancer Prevention Trial design might account for the greater percentage of Gleason grade tumors in the study arm, morphologic changes due to long-term finasteride treatment were not a likely cause.

  12. 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

  13. Prevention of Prostate Cancer by Inositol Hexaphosphate

    DTIC Science & Technology

    2007-02-01

    signaling pathways therby inhibit growth. A large number of studies have pointed out that inositol hexaphosphate ( IP6 ) could have beneficial effect on...years, a large number of studies have pointed out that inositol hexaphosphate ( IP6 ), the most abundant phosphorylated inositol present in beans, cereal... inositol hexaphosphate ( IP6 ) on the growth and development of prostate cancer in TRAMP mice. To test the efficacy of IP6 in preventing prostate cancer

  14. Effects of radiation on the incidence of prostate cancer among Nagasaki atomic bomb survivors.

    PubMed

    Kondo, Hisayoshi; Soda, Midori; Mine, Mariko; Yokota, Kenichi

    2013-10-01

    Atomic bomb survivors have been reported to have an increased risk of some cancers, especially leukemia. However, the risk of prostate cancer in atomic bomb survivors is not known to have been examined previously. This study examined the association between atomic bomb radiation and the incidence of prostate cancer among male Nagasaki atomic bomb survivors. The subjects were classified by distance from the hypocenter into a proximal group (<2 km), a distal group (≥2 km), and an early entrance group (those who entered the region <2 km from the hypocenter within 2 weeks after the explosion). Between 1996 and 2009, 631 new cases of prostate cancer were identified among approximately 18 400 male Nagasaki atomic bomb survivors who were alive in 1996. The Cox proportional hazard model was used to estimate the risk of prostate cancer development, with adjustment for age at atomic bomb explosion, attained age, smoking status, and alcohol consumption. Compared with the distal group, the proximal group had significant increased risks of total, localized, and high-grade prostate cancer (relative risk and 95% confidence interval: 1.51 [1.21-1.89]; 1.80 [1.26-2.57]; and 1.88 [1.20-2.94], respectively). This report is the first known to reveal a significant relationship between atomic bomb radiation and prostate cancer. © 2013 Japanese Cancer Association.

  15. Accumulation of Palmitoylcarnitine and Its Effect on Pro‐Inflammatory Pathways and Calcium Influx in Prostate Cancer

    PubMed Central

    Al‐Bakheit, Ala'a; Traka, Maria; Saha, Shikha; Mithen, Richard

    2016-01-01

    BACKGROUND Acylcarnitines are intermediates of fatty acid oxidation and accumulate as a consequence of the metabolic dysfunction resulting from the insufficient integration between β‐oxidation and the tricarboxylic acid (TCA) cycle. The aim of this study was to investigate whether acylcarnitines accumulate in prostate cancer tissue, and whether their biological actions could be similar to those of dihydrotestosterone (DHT), a structurally related compound associated with cancer development. METHODS Levels of palmitoylcarnitine (palcar), a C16:00 acylcarnitine, were measured in prostate tissue using LC‐MS/MS. The effect of palcar on inflammatory cytokines and calcium (Ca2+) influx was investigated in in vitro models of prostate cancer. RESULTS We observed a significantly higher level of palcar in prostate cancerous tissue compared to benign tissue. High levels of palcar have been associated with increased gene expression and secretion of the pro‐inflammatory cytokine IL‐6 in cancerous PC3 cells, compared to normal PNT1A cells. Furthermore, we found that high levels of palcar induced a rapid Ca2+ influx in PC3 cells, but not in DU145, BPH‐1, or PNT1A cells. This pattern of Ca2+ influx was also observed in response to DHT. Through the use of whole genome arrays we demonstrated that PNT1A cells exposed to palcar or DHT have a similar biological response. CONCLUSIONS This study suggests that palcar might act as a potential mediator for prostate cancer progression through its effect on (i) pro‐inflammatory pathways, (ii) Ca2+ influx, and (iii) DHT‐like effects. Further studies need to be undertaken to explore whether this class of compounds has different biological functions at physiological and pathological levels. Prostate 76:1326–1337, 2016. © 2016 The Authors. The Prostate published by Wiley Periodicals, Inc. PMID:27403764

  16. Combined effects of terazosin and genistein on a metastatic, hormone-independent human prostate cancer cell line.

    PubMed

    Chang, Kee-Lung; Cheng, Hsiao-Ling; Huang, Li-Wen; Hsieh, Bau-Shan; Hu, Yu-Chen; Chih, Tsai-Tung; Shyu, Huey-Wen; Su, Shu-Jem

    2009-04-08

    Metastatic prostate cancer progresses from androgen-dependent to androgen-independent. Terazosin, a long-acting selective alpha1-adrenoreceptor antagonist, induces apoptosis of prostate cancer cells in an alpha1-adrenoreceptor-independent manner, while genistein, a major soy isoflavone, inhibits the growth of several types of cancer cells. The present study was designed to test the therapeutic potential of a combination of terazosin and genistein using a metastatic, hormone-independent prostatic cancer cell line, DU-145. Terazosin or genistein treatment inhibited the growth of DU-145 cells in a dose-dependent manner, whereas had no effect on normal prostate epithelial cells. Addition of 1 microg/ml of terazosin, which was inactive alone, augmented the growth inhibitory effect of 5 microg/ml of genistein. Co-treatment with terazosin resulted in the genistein-induced arrest of DU-145 cells in G2/M phase being overridden and an increase in apoptotic cells, as evidenced by procaspase-3 activation and PARP cleavage. The combination also caused a greater decrease in the levels of the apoptosis-regulating protein, Bcl-XL, and of VEGF165 and VEGF121 than genistein alone. In conclusion, the terazosin/genistein combination was more effective in inhibiting cell growth and VEGF expression as well as inducing apoptosis of the metastatic, androgen-independent prostate cancer cell line, DU-145, than either alone. The doses used in this study are in lower and nontoxic anticancer dosage range, suggesting this combination has potential for therapeutic use.

  17. Calcium intake and prostate cancer among African Americans: effect modification by vitamin D receptor calcium absorption genotype.

    PubMed

    Rowland, Glovioell W; Schwartz, Gary G; John, Esther M; Ingles, Sue Ann

    2012-01-01

    High dietary intake of calcium has been classified as a probable cause of prostate cancer, although the mechanism underlying the association between dietary calcium and prostate cancer risk is unclear. The vitamin D receptor (VDR) is a key regulator of calcium absorption. In the small intestine, VDR expression is regulated by the CDX-2 transcription factor, which binds a polymorphic site in the VDR gene promoter. We examined VDR Cdx2 genotype and calcium intake, assessed by a food frequency questionnaire, in 533 African-American prostate cancer cases (256 with advanced stage at diagnosis, 277 with localized stage) and 250 African-American controls who participated in the California Collaborative Prostate Cancer Study. We examined the effects of genotype, calcium intake, and diet-gene interactions by conditional logistic regression. Compared with men in the lowest quartile of calcium intake, men in the highest quartile had an approximately twofold increased risk of localized and advanced prostate cancer (odds ratio [OR] = 2.20, 95% confidence interval [CI] = 1.40, 3.46), with a significant dose-response. Poor absorbers of calcium (VDR Cdx2 GG genotype) had a significantly lower risk of advanced prostate cancer (OR = 0.41, 95% CI = 0.19, 0.90). The gene-calcium interaction was statistically significant (p = 0.03). Among men with calcium intake below the median (680 mg/day), carriers of the G allele had an approximately 50% decreased risk compared with men with the AA genotype. These findings suggest a link between prostate cancer risk and high intestinal absorption of calcium.

  18. Calcium Intake and Prostate Cancer Among African Americans: Effect Modification by Vitamin D Receptor Calcium Absorption Genotype

    PubMed Central

    Rowland, Glovioell W.; Schwartz, Gary G.; John, Esther M.; Ingles, Sue Ann

    2011-01-01

    High dietary intake of calcium has been classified as a probable cause of prostate cancer although the mechanism underlying the association between dietary calcium and prostate cancer risk is unclear. The vitamin D receptor (VDR) is a key regulator of calcium absorption. In the small intestine, VDR expression is regulated by the CDX-2 transcription factor, which binds a polymorphic site in the VDR gene promoter. We examined VDR Cdx2 genotype and calcium intake, assessed by a food frequency questionnaire, in 533 African American prostate cancer cases (256 with advanced stage at diagnosis, 277 with localized stage) and 250 African American controls who participated in the California Collaborative Prostate Cancer Study. We examined the effects of genotype, calcium intake, and diet-gene interactions by conditional logistic regression. Compared to men in the lowest quartile of calcium intake, men in the highest quartile had an approximately two-fold increased risk of localized and advanced prostate cancer (odds ratio [OR]= 2.20, 95% confidence interval [CI]= 1.40, 3.46), with a significant dose-response. Poor absorbers of calcium (VDR Cdx2 GG genotype) had a significantly lower risk of advanced prostate cancer (OR= 0.41, 95% CI = 0.19, 0.90). The gene-calcium interaction was statistically significant (p=0.03). Among men with calcium intake below the median (680 mg/day), carriers of the G allele had an approximately 50% decreased risk compared to men with the AA genotype. These findings suggest a link between prostate cancer risk and high intestinal absorption of calcium. PMID:21887707

  19. Effect of curcumin on Bcl-2 and Bax expression in nude mice prostate cancer.

    PubMed

    Yang, Jiayi; Ning, Jianping; Peng, Linlin; He, Dan

    2015-01-01

    Prostate cancer is a common malignant tumor in urinary system. Curcumin has curative effect on many kinds of cancers and can inhibit prostate cancer (PC)-3 cells proliferation. This study aimed to explore the curcumin induced prostate cancer cell apoptosis and apoptosis related proteins Bcl-2 and Bax expression. PC-3 cells were injected subcutaneously to the nude mice to establish the tumor model. The nude mice were randomly divided into group C (normal saline), group B (6% polyethylene glycol and 6% anhydrous ethanol), group H, M, L (100 mg/kg, 50 mg/kg, and 25 mg/kg curcumin). The tumor volume was measured every 6 days to draw the tumor growth curve. The mice were killed at the 30(th) day after injection to weight the tumor. TUNEL assay was applied to determine cell apoptosis. Immunohistochemistry was used to detect Bcl-2 and Bax expression. The tumor volume and weight in group H, M, L were significantly lower than the control group (C, B) (P<0.05), and the inhibitory rate increased following the curcumin dose increase. Compared with the control group, Bcl-2 expression in group H, M, L gradually decreased, while Bax protein expression increased (P<0.05). The cell apoptosis rate showed no statistical difference between group B and C, while it increased in curcumin group H, M, and L (P<0.05). Curcumin could inhibit PC-3 growth, decrease tumor volume, reduce tumor weight, and induce cell apoptosis under the skin of nude mice by up-regulating Bax and down-regulating Bcl-2.

  20. Effect of curcumin on Bcl-2 and Bax expression in nude mice prostate cancer

    PubMed Central

    Yang, Jiayi; Ning, Jianping; Peng, Linlin; He, Dan

    2015-01-01

    Prostate cancer is a common malignant tumor in urinary system. Curcumin has curative effect on many kinds of cancers and can inhibit prostate cancer (PC)-3 cells proliferation. This study aimed to explore the curcumin induced prostate cancer cell apoptosis and apoptosis related proteins Bcl-2 and Bax expression. PC-3 cells were injected subcutaneously to the nude mice to establish the tumor model. The nude mice were randomly divided into group C (normal saline), group B (6% polyethylene glycol and 6% anhydrous ethanol), group H, M, L (100 mg/kg, 50 mg/kg, and 25 mg/kg curcumin). The tumor volume was measured every 6 days to draw the tumor growth curve. The mice were killed at the 30th day after injection to weight the tumor. TUNEL assay was applied to determine cell apoptosis. Immunohistochemistry was used to detect Bcl-2 and Bax expression. The tumor volume and weight in group H, M, L were significantly lower than the control group (C, B) (P<0.05), and the inhibitory rate increased following the curcumin dose increase. Compared with the control group, Bcl-2 expression in group H, M, L gradually decreased, while Bax protein expression increased (P<0.05). The cell apoptosis rate showed no statistical difference between group B and C, while it increased in curcumin group H, M, and L (P<0.05). Curcumin could inhibit PC-3 growth, decrease tumor volume, reduce tumor weight, and induce cell apoptosis under the skin of nude mice by up-regulating Bax and down-regulating Bcl-2. PMID:26464676

  1. Synergistic cytotoxic effects of zoledronic acid and radiation in human prostate cancer and myeloma cell lines

    SciTech Connect

    Algur, Ece; Macklis, Roger M.; Haefeli, Urs O. . E-mail: uhafeli@interchange.ubc.ca

    2005-02-01

    Purpose: The clinical use of the potent bisphosphonate zoledronic acid has increased recently, especially for the treatment of bone metastases. Synergistic effects with chemotherapeutic agents (e.g., doxorubicin, paclitaxel) have been shown. It is not known whether similar synergistic effects exist with radiation. Methods and materials: IM-9 myeloma cells and C4-2 prostate cancer cells were treated with up to 200 {mu}M concentrations of zoledronic acid, irradiated with single doses of up to 1,000 cGy, or exposed to combinations of both treatments. Cell viability was then determined via yellow dye 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assay and the affected fractions analyzed using the median effect principal, a method developed and validated by Chou and Talalay. Results: A statistically significant synergistic cytotoxic effect of the combination of zoledronic acid and radiation was documented. The extent of the effect was cell type-dependent, with the C4-2 cells showing a greater synergistic effect than the IM-9 cells. Conclusions: The combined use of zoledronic acid and radiotherapy shows enhanced in vitro cytotoxicity for two human prostate and myeloma cancer cell lines over that expected for a simple additive effect from each treatment alone. A clinical trial is under way to test this combination therapy.

  2. Antiproliferative effect of polyphenols and sterols of virgin argan oil on human prostate cancer cell lines.

    PubMed

    Bennani, H; Drissi, A; Giton, F; Kheuang, L; Fiet, J; Adlouni, A

    2007-01-01

    The aim of our study has to evaluate the antiproliferative effect of polyphenols and sterols extracted from the virgin argan oil on three human prostatic cell lines (DU145, LNCaP, and PC3). Cytotoxicity, anti-proliferative effects and nuclear morphological changes of cells were analyzed after treatment with sterols and polyphenols. The results were compared to 2-methoxyestradiol (2ME(2)) as positive control. Polyphenols and sterols of virgin argan oil and 2ME(2) exhibited a dose-response cytotoxic effect and antiproliferative action on the three tested cell lines. The antiproliferative effect of polyphenols was similar for the DU145 and LNCaP cell lines; the GI(50) (defined as the concentration inhibiting growth by 50% in comparison with the control) was respectively 73 and 70microg/ml. The antiproliferative effect of sterols was 46 and 60microg/ml as GI(50) for the DU145 and LNCaP cell lines. For the PC3 cell line, the best antiproliferative effect was obtained by argan sterols with GI(50)=43microg/ml. On the other hand, the nuclear morphology analyses have shown an increased proportion of pro-apoptotic of nuclei in LNCaP cell treated with IC(50) of polyphenols or sterols compared to control cells. Our results show for the first time the antiproliferative and pro-apoptotic effects of polyphenols and sterols extracted from virgin argan oil and confirm the antiproliferative and pro-apoptotic effects of 2ME(2) on prostate cancer cell lines. These data suggest that argan oil may be interesting in the development of new strategies for prostate cancer prevention.

  3. Bortezomib and etoposide combinations exert synergistic effects on the human prostate cancer cell line PC-3

    PubMed Central

    ARAS, BEKIR; YERLIKAYA, AZMI

    2016-01-01

    Novel treatment modalities are urgently required for androgen-independent prostate cancer. In order to develop an alternative treatment for prostate cancer, the cytotoxic effects of the 26S proteasome inhibitor bortezomib, either alone or in combination with the two commonly used chemotherapeutic agents irinotecan and etoposide, on the human prostate cancer cell line PC-3 were evaluated in the present study. The PC-3 cell line was maintained in Dulbecco's modified Eagle's medium with 10% fetal bovine serum and treated with various doses of bortezomib, irinotecan, etoposide or their combinations. The growth inhibitory and cytotoxic effects were determined by water-soluble tetrazolium (WST)-1 assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay or iCELLigence system. The combination index values were determined by the Chou-Talalay method. The half maximal inhibitory concentration (IC50) value of bortezomib on the PC-3 cell line was determined to be 53.4 nM by WST-1 assay, whereas the IC50 values of irinotecan and etoposide were determined to be 2.1 and 26.5 µM, respectively. These results suggest that the 26S proteasome inhibitor bortezomib is more potent, compared with irinotecan and etoposide, in the androgen-insensitive and tumor protein p53-null cell line PC-3. The combined effects of bortezomib+irinotecan and bortezomib+etoposide were also tested on PC-3 cells. The effect of bortezomib+irinotecan combination was not significantly different than that produced by either monotherapy, according to the results of iCELLigence system and MTT assay. However, 40 nM bortezomib+5 µM etoposide or 40 nM bortezomib+20 µM etoposide combinations were observed to be more effective than each drug tested alone. The results of the current study suggest that bortezomib and etoposide combination may be additionally evaluated in clinical trials for the treatment of hormone-refractory prostate cancer. PMID:27123085

  4. 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

  5. Milk consumption in relation to incidence of prostate, breast, colon, and rectal cancers: is there an independent effect?

    PubMed

    Zhang, Jianjun; Kesteloot, Hugo

    2005-01-01

    Milk contains a wide variety of ingredients, such as nutrients, hormones, and chemical contaminants. Whether milk consumption is associated with the risk of prostate, breast, colon, and rectal cancers is unclear and was evaluated in this study. Data on milk consumption for 9 time periods (1964-1994) and incidence rates of prostate, female breast, colon, and rectal cancers, mostly around 1993-1997, in 38 countries were obtained from the Food and Agriculture Organization and World Health Organization, respectively. Milk consumption was strongly correlated with incidence rates of prostate cancer (r = 0.65-0.69; all P < 0.0001) and breast cancer (r = 0.64-0.74; all P < 0.0001) in all the nine time periods examined. A modest positive correlation was found for colon and rectal cancers in both sexes (all P < 0.05, except for rectal cancer in the first three time periods). The previous findings remained essentially unchanged after adjustment for vegetable, alcohol, and cigarette consumption but disappeared after further adjustment for non-milk fat consumption, except for breast cancer in the last three time periods. The present study does not support an overall substantial effect of milk consumption on the risk of prostate, breast, colon, and rectal cancers at the population level.

  6. The economic effect of using magnetic resonance imaging and magnetic resonance ultrasound fusion biopsy for prostate cancer diagnosis.

    PubMed

    Hutchinson, Ryan C; Costa, Daniel N; Lotan, Yair

    2016-07-01

    Prostate magnetic resonance imaging (MRI) is a maturing imaging modality that has been used to improve detection and staging of prostate cancer. The goal of this review is to evaluate the economic effect of the use of MRI and MRI fusion in the diagnosis of prostate cancer. A literature review was used to identify articles regarding efficacy and cost of MRI and MRI-guided biopsies. There are currently a limited number of studies evaluating cost of incorporating MRI into clinical practice. These studies are primarily models projecting cost estimates based on meta-analyses of the literature. There is considerable variance in the effectiveness of MRI-guided biopsies, both cognitive and fusion, based on user experience, type of MRI (3T vs. 1.5T), use of endorectal coil and type of scoring system for abnormalities such that there is still potential for improvement in accuracy. There is also variability in assumed costs of incorporating MRI into clinical practice. The addition of MRI to the diagnostic algorithm for prostate cancer has caused a shift in how we understand the disease and in what tumors are found on initial and repeat biopsies. Further risk stratification may allow more men to pursue noncurative therapy, which in and of itself is cost-effective in properly selected men. As prostate cancer care comes under increasing scrutiny on a national level, there is pressure on providers to be more accurate in their diagnoses. This in turn can lead to additional testing including Multiparametric MRI, which adds upfront cost. Whether the additional cost of prostate MRI is warranted in detection of prostate cancer is an area of intense research. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Effect of a HIF-1 Alpha Polymorphism on the Incidence and Prostate Cancer

    DTIC Science & Technology

    2007-02-01

    factor levels and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 2005;14(6):1557-1561. 34. Percy MJ, Mooney SM, McMullin MF, Flores A...vascular endothelial growth factor in pathological angiogenesis. Breast Cancer Research & Treatment 1995;36(2):127-137. 37. Jackson MW, Bentel JM, Tilley

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

    PubMed

    Kotb, Ahmed Fouad; Beltagy, Ahmad; Ismail, Asmaa Mohamed; Hashad, Mohamed Mohie

    2015-09-30

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

  9. Effects of Marine Phospholipids Extract on the Lipid Levels of Metastatic and Nonmetastatic Prostate Cancer Patients

    PubMed Central

    Taylor, Lenka A.; Kluth, Jessica; Hübschle, Tobias; Fritzsche, Jonas; Hildenbrand, Bernd; Pletschen, Lars; Schilli, Karin; Hodina, Arwen; Griffith, Lee S.; Breul, Jürgen

    2014-01-01

    High intake of omega-3 fatty acids (n-3 FAs) from fish has shown to reduce metastatic progression of prostate cancer. This clinical trial investigated the influence of high n-3 FA intake (marine phospholipids, MPL) on the FA composition of blood lipids, lysophosphatidylcholine (LPC), and on lipoproteins in prostate cancer patients and elderly men without prostate cancer. MPL supplementation resulted in a significant increase of n-3 FAs (eicosapentaenoic and docosahexaenoic acid) in blood lipids, while arachidonic acid (n-6 FA) decreased significantly. Low density lipoprotein (LDL) and high density lipoprotein (HDL) increased significantly, but the LDL increase was observed only in subjects with an inactive tumour. Similarly, LPC plasma concentration increased significantly only in patients without tumour. The missing increase of LDL and LPC after MPL supplementation in patients with actively growing (metastasizing) prostate cancer suggests that tumour cells have an elevated demand for LDL and LPC. Due to the MPL-induced increase of n-3 FAs in these blood lipids, it can be assumed that especially actively growing and metastasizing prostate cancer cells are provided with elevated amounts of these antimetastatic n-3 FAs. A hypothetic model explaining the lower incidence of metastatic progression in prostate cancer patients with high fish consumption is presented. PMID:27351011

  10. Medical hospitalizations in prostate cancer survivors.

    PubMed

    Gnanaraj, Jerome; Balakrishnan, Shobana; Umar, Zarish; Antonarakis, Emmanuel S; Pavlovich, Christian P; Wright, Scott M; Khaliq, Waseem

    2016-07-01

    The objectives of the study were to explore the context and reasons for medical hospitalizations among prostate cancer survivors and to study their relationship with obesity and the type of prostate cancer treatment. A retrospective review of medical records was performed at an academic institution for male patients aged 40 years and older who were diagnosed and/or treated for prostate cancer 2 years prior to the study's observation period from January 2008 to December 2010. Unpaired t test, ANOVA, and Chi-square tests were used to compare patients' characteristics, admission types, and medical comorbidities by body mass index (BMI) and prostate cancer treatment. Mean age for the study population was 76 years (SD = 9.2). Two hundred and forty-five prostate cancer survivors were stratified into two groups: non-obese (BMI < 30 kg/m(2)) and obese (BMI ≥ 30 kg/m(2)). The study population's characteristics analyzed by BMI were similar including Gleason score, presence of metastatic disease and genitourinary-related side effects. Only 13 % of admissions were for complaints related to their genitourinary system. Neither the specific treatment that the patients had received for their prostate cancer, nor obesity was associated with the reasons for their medical admission. Survivorship after having a diagnosis of prostate cancer is often lengthy, and these men are at risk of being hospitalized, as they get older. From this inquiry, it has become clear that neither body mass index nor prior therapy is associated with specific admission characteristics, and only a minority of such admissions was directly related to prostate cancer or the genitourinary tract.

  11. Effects of a human plasma membrane-associated sialidase siRNA on prostate cancer invasion

    SciTech Connect

    Li, Xiaojie; Zhang, Ling; Shao, Yueting; Liang, Zuowen; Shao, Chen; Wang, Bo; Guo, Baofeng; Li, Na; Zhao, Xuejian; Li, Yang; Xu, Deqi

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer Neu3 is as one of the sialidases and regulates cell surface functions. Black-Right-Pointing-Pointer A Neu3-specific siRNA inhibited prostrate cancer cell invasion and migration. Black-Right-Pointing-Pointer The Neu3-specific siRNA inhibited prostate cancer metastasis in mice. Black-Right-Pointing-Pointer Targeting Neu3 may have utility for gene-based therapy of human cancer metastasis. -- Abstract: Human plasma membrane-associated sialidase (Neu3) is one of several sialidases that hydrolyze sialic acids in the terminal position of the carbohydrate groups of glycolipids and glycoproteins. Neu3 is mainly localized in plasma membranes and plays crucial roles in the regulation of cell surface functions. In this study, we investigated the effects and molecular mechanisms of Neu3 on cell invasion and migration in vivo and in vitro. Initially, we found that the levels of Neu3 expression were higher in prostate cancer tissues and cell lines than in normal prostate tissues based on RT-PCR and Western blotting analyses. We then applied a Neu3 siRNA approach to block Neu3 signaling using PC-3M cells as model cells. Transwell invasion assays and wound assays showed significantly decreased invasion and migration potential in the Neu3 siRNA-transfected cells. RT-PCR and Western blotting analyses revealed that Neu3 knockdown decreased the expressions of the matrix metalloproteinases MMP-2 and MMP-9. In vivo, mice injected with PC-3M cell tumors were evaluated by SPECT/CT to determine the presence of bone metastases. Mice treated with attenuated Salmonella carrying the Neu3 siRNA developed fewer bone metastases than mice treated with attenuated Salmonella carrying a control Scramble siRNA, attenuated Salmonella alone or PBS. The results for bone metastasis detection by pathology were consistent with the data obtained by SPECT/CT. Tumor blocks were evaluated by histochemical, RT-PCR and Western blotting analyses. The results revealed

  12. 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.

  13. 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.

  14. Effects of occupational therapy on quality of life of patients with metastatic prostate cancer

    PubMed Central

    Huri, Meral; Huri, Emre; Kayihan, Hulya; Altuntas, Onur

    2015-01-01

    Objectives: To evaluate the efficiency of occupational therapy relative to a home program in improving quality of life (QoL) among men who were treated for metastatic prostate cancer (MPC). Methods: Fifty-five men were assigned randomly to either the 12-week cognitive behavioral therapy based occupational therapy (OT-CBSM) intervention (treatment group) or a home program (control group) between March 2012 and August 2014 in the Department of Occupational Therapy, Faculty of Health Sciences, Hacettepe University, Ankara, Turkey. The Canadian Occupational Performance Measure (COPM) was used to measure the occupational performance and identify difficulties in daily living activities. The QoL and symptom status were measured by The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 and its Prostate Cancer Module. A 12-week OT-CBSM intervention including client-centered training of daily living activities, recreational group activities, and cognitive behavioral stress management intervention were applied. Results: The COPM performance and satisfaction scores, which indicate occupational participation and QoL increased statistically in the treatment group in relation to men who were included in the home-program (p≤0.05). Conclusion: A 12-week OT-CBSM intervention was effective in improving QoL in men treated for MPC, and these changes were associated significantly with occupational performance. PMID:26219446

  15. Apoptotic and anti-angiogenic effects of Salvia triloba extract in prostate cancer cell lines.

    PubMed

    Atmaca, Harika; Bozkurt, Emir

    2016-03-01

    Plants, due to their remarkable composition, are considered as natural resources of bioactive compounds with specific biological activities. Salvia genus (Lamiaceae) has been used around the world in complementary medicine since ancient times. We investigated the cytotoxic, apoptotic and anti-angiogenic effects of methanolic Salvia triloba extract (STE) in prostate cancer cells. Cell viability was evaluated by XTT; apoptosis was investigated by DNA fragmentation and caspase 3/7 activity assays. Changes in the angiogenic cytokine levels were investigated by human angiogenesis antibody array. Scratch assay was used to determine the cell motility. STE induced cytotoxicity and apoptosis in a concentration-dependent manner in both cancer cells; however, it was not cytotoxic to normal cells. Cell motility was reduced in PC-3, DU-145 and HUVEC cells by STE treatment. ANG, ENA-78, bFGF, EGF, IGF-1 and VEGF-D levels were significantly decreased by -2.9, -3.7, -1.7, -1.7, -2.0 and -1.8 fold in STE-treated DU-145 cells, however, ANG, IL-8, LEP, RANTES, TIMP-1, TIMP-2 and VEGF levels were significantly decreased by -5.1, -2.0, -2.4, -3.1, -1.5, -2.0 and -2.5 fold in PC-3 cells. These data suggest that STE might be a promising candidate for anti-tumor and anti-angiogenic treatment of prostate cancer.

  16. Apoptotic effects of cooked and in vitro digested soy on human prostate cancer cells.

    PubMed

    Dong, Xin; Xu, Wenqing; Sikes, Robert A; Wu, Changqing

    2012-12-01

    Previous laboratory and animal studies reported that soy isoflavones were major bioactive compounds in soy to exert chemoprotection of prostate cancer. However, these studies cannot reflect the realistic effects that soy may induce through diets, and little is known about the bioavailability of isoflavones from whole soy food and their bioactivities after cooking and digestion. In this study, cooking and in vitro digestion were used to prepare soy extracts and the effects of cooking and digestion on the isoflavone contents and bioactivities of the whole soy extracts were examined. The cooking procedure generally increased the amount of daidzin, genistin and daidzein, but decreased that of genistein. Digestion process significantly lowered contents of daidzin and genistin in 60min cooked sample, while increased the contents of daidzin and daidzein and decreased the content of genistein in the uncooked sample. Antioxidant activities of soy extracts increased after cooking and in vitro digestion, while no consistent increase of the four soy isoflavones was determined. The apoptotic effects of soy extracts on both LNCaP and C4-2B cells were generally in a dose-dependent manner. Compared to purified single isoflavones, cooked and digested soy were more effective on induction of prostate cancer cell apoptosis, which indicated synergistic interactions between various bioactive compounds in the whole soy.

  17. DNA Damage and Genetic Instability as Harbingers of Prostate Cancer

    DTIC Science & Technology

    2013-01-01

    incidence of prostate cancer as compared to placebo . Primary analysis of this trial indicated no statistically significant effect of selenium...sample of patients that participated in a Phase 2 clinical trial investigating the effect of selenium supplementation on prostate cancer progression...Results of this trial indicated that selenium did not have an effect on prostate cancer aggressiveness as measured by PSA velocity and hence biopsy

  18. Interpatient variation in normal peripheral zone apparent diffusion coefficient: effect on the prediction of prostate cancer aggressiveness.

    PubMed

    Litjens, Geert J S; Hambrock, Thomas; Hulsbergen-van de Kaa, Christina; Barentsz, Jelle O; Huisman, Henkjan J

    2012-10-01

    To determine the interpatient variability of prostate peripheral zone (PZ) apparent diffusion coefficient (ADC) and its effect on the assessment of prostate cancer aggressiveness. The requirement for institutional review board approval was waived. Intra- and interpatient variation of PZ ADCs was determined by means of repeated measurements of normal ADCs at three magnetic resonance (MR) examinations in a retrospective cohort of 10 consecutive patients who had high prostate-specific antigen levels and negative findings at transrectal ultrasonographically-guided biopsy. In these patients, no signs of PZ cancer were found at all three MR imaging sessions. The effect of interpatient variation on the assessment of prostate cancer aggressiveness was examined in a second retrospective cohort of 51 patients with PZ prostate cancer. Whole-mount step-section pathologic evaluation served as reference standard for placement of regions of interest on tumors and normal PZ. Repeated-measures analysis of variance was used to determine the significance of the interpatient variations in ADCs. Linear logistic regression was used to assess whether incorporating normal PZ ADCs improves the prediction of cancer aggressiveness. Analysis of variance revealed that interpatient variability (1.2-2.0×10(-3) mm2/sec) was significantly larger than measurement variability (0.068×10(-3) mm2/sec±0.027 [standard deviation]) (P=.0058). Stand-alone tumor ADCs showed an area under the receiver operating characteristic curve (AUC) of 0.91 for discriminating low-grade versus high-grade tumors. Incorporating normal PZ ADC significantly improved the AUC to 0.96 (P=.0401). PZ ADCs show significant interpatient variation, which has a substantial effect on the prediction of prostate cancer aggressiveness. Correcting this effect results in a significant increase in diagnostic accuracy. © RSNA, 2012.

  19. Tissue Effects in a Randomized Controlled Trial of Short-term Finasteride in Early Prostate Cancer.

    PubMed

    Kim, Jeri; Davis, John W; Klein, Eric A; Magi-Galluzzi, Cristina; Lotan, Yair; Ward, John F; Pisters, Louis L; Basler, Joseph W; Pettaway, Curtis A; Stephenson, Andrew; Li Ning Tapia, Elsa M; Efstathiou, Eleni; Wang, Xuemei; Do, Kim-Anh; Lee, J Jack; Gorlov, Ivan P; Vornik, Lana A; Hoque, Ashraful M; Prokhorova, Ina N; Parnes, Howard L; Lippman, Scott M; Thompson, Ian M; Brown, Powel H; Logothetis, Christopher J; Troncoso, Patricia

    2016-05-01

    In the Prostate Cancer Prevention Trial, finasteride selectively suppressed low-grade prostate cancer and significantly reduced the incidence of prostate cancer in men treated with finasteride compared with placebo. However, an apparent increase in high-grade disease was also observed among men randomized to finasteride. We aimed to determine why and hypothesized that there is a grade-dependent response to finasteride. From 2007 to 2012, we randomized dynamically by intranet-accessible software 183 men with localized prostate cancer to receive 5mg finasteride or placebo daily in a double-blind study during the 4-6weeks preceding prostatectomy. As the primary end point, the expression of a predefined molecular signature (ERβ, UBE2C, SRD5A2, and VEGF) differentiating high- and low-grade tumors in Gleason grade (GG) 3 areas of finasteride-exposed tumors from those in GG3 areas of placebo-exposed tumors, adjusted for Gleason score (GS) at prostatectomy, was compared. We also determined androgen receptor (AR) levels, Ki-67, and cleaved caspase 3 to evaluate the effects of finasteride on the expression of its downstream target, cell proliferation, and apoptosis, respectively. The expression of these markers was also compared across grades between and within treatment groups. Logistic regression was used to assess the expression of markers. We found that the predetermined molecular signature did not distinguish GG3 from GG4 areas in the placebo group. However, AR expression was significantly lower in the GG4 areas of the finasteride group than in those of the placebo group. Within the finasteride group, AR expression was also lower in GG4 than in GG3 areas, but not significantly. Expression of cleaved caspase 3 was significantly increased in both GG3 and GG4 areas in the finasteride group compared to the placebo group, although it was lower in GG4 than in GG3 areas in both groups. We showed that finasteride's effect on apoptosis and AR expression is tumor grade dependent

  20. 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.

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

    DTIC Science & Technology

    2009-03-01

    through direct cellular toxicity and the release of inflammatory cytokines 24. Likewise, T cells directed against Helicobacter pylori are thought to...systemic T-cell response to Helicobacter pylori in gastric cancer patients is characterised by production of interleukin-10. Clin Immunol 2007;125:205...Xue LJ, Su QS, Yang JH, Lin Y. Autoimmune responses induced by Helicobacter pylori improve the prognosis of gastric carcinoma. Med Hypotheses

  2. The association of long-term treatment-related side effects with cancer-specific and general quality of life among prostate cancer survivors.

    PubMed

    Davis, Kimberly M; Kelly, Scott P; Luta, George; Tomko, Catherine; Miller, Anthony B; Taylor, Kathryn L

    2014-08-01

    To examine the association between treatment-related side effects and cancer-specific and general quality of life (QOL) among long-term prostate cancer survivors. Within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we conducted telephone interviews with prostate cancer survivors (N = 518) who were 5-10 years after diagnosis. We assessed demographic and clinical information, sexual, urinary, and bowel treatment-related side effects (Expanded Prostate Cancer Index Composite), cancer-specific QOL (Functional Assessment of Cancer Therapy--total score), and general QOL (the Medical Outcomes Study Short Form 12's physical and mental subscales). Participants were aged 74.6 years on average, primarily White (88.4%), and married (81.7%). Pearson correlation coefficients between the 3 treatment-related side effect domains (urinary, sexual, and bowel) and QOL ranged between 0.14 and 0.42 (P <.0001). Multivariable linear regression analyses revealed that poorer urinary and sexual functioning and greater bowel side effects were independently associated with poorer cancer-specific QOL (P <.0001). Bowel and urinary functions were also associated with poorer general QOL on the Medical Outcomes Study Short Form 12's physical component summary and mental component summary (P <.05). Bowel side effects demonstrated the strongest association with all QOL outcomes. Treatment-related side effects persisted for up to 10 years after diagnosis and continued to be associated with men's QOL. These results suggest that each of the treatment-related side effects was independently associated with cancer-specific QOL. Compared with the other Expanded Prostate Cancer Index Composite domains, bowel side effects had the strongest association with cancer-specific and general QOL. These associations emphasize the tremendous impact that bowel side effects continue to have for men many years after their initial diagnosis. Copyright © 2014. Published by Elsevier Inc.

  3. Development of prostate cancer treatment: the good news.

    PubMed

    Denmeade, Samuel R; Isaacs, John T

    2004-02-15

    Prostate cancer is the most commonly diagnosed cancer in American men representing one-third of all new cancer cases each year. This translates into one out of every six American men being diagnosed with prostate cancer over the course of their lifetimes. Over 31,000 of these men die each year from prostate cancer. Before the 1980's, 50% of men were diagnosed with widespread metastatic disease and there were few therapeutic choices for patients. The good news for patients is that, over the last 30 years there have been significant advances in detection and prognostication as well as major improvements in the surgical, radiation, and medical oncological management of prostate cancer. This review describes the evolution of these therapeutic modalities for prostate cancer. This evolution has been driven by the explosion of knowledge concerning cancer in general and in the specific biology of prostate cancer in particular over the last 30 years. This knowledge has been obtained by concentrating human and financial resources in organ specific studies of the prostate. The end result of this effort is that, today, 85% of new prostate cancer cases are diagnosed at local and regional stages and the 5-year relative prostate cancer survival rate has increased by 20% since 1985. In addition, the therapeutic approach to prostate cancer can now be individualized based on the characteristics of the patient's disease. Finally, recent data suggest that the death rate from prostate cancer is decreasing by approximately 4% per year since 1994. Further good news for patients is that new discoveries about the biology of prostate cancer are rapidly being translated into new therapies, a large number of which are currently being tested in clinical trials. Continued allocation of appropriate human and material resources should yield new, more effective therapies for prostate cancer that will further impact patient quality of life and survival in the 21st century. Copyright 2004 Wiley

  4. The effect of the USPSTF PSA screening recommendation on prostate cancer incidence patterns in the USA.

    PubMed

    Fleshner, Katherine; Carlsson, Sigrid V; Roobol, Monique J

    2017-01-01

    Guidelines regarding recommendations for PSA screening for early detection of prostate cancer are conflicting. In 2012, the United States Preventive Services Task Force (USPSTF) assigned a grade of D (recommending against screening) for men aged ≥75 years in 2008 and for men of all ages in 2012. Understanding temporal trends in rates of screening before and after the 2012 recommendation in terms of usage patterns in PSA screening, changes in prostate cancer incidence and biopsy patterns, and how the recommendation has influenced physician's and men's attitudes about PSA screening and subsequent ordering of other screening tests is essential within the scope of prostate cancer screening policy. Since the 2012 recommendation, rates of PSA screening decreased by 3-10% in all age groups and across most geographical regions of the USA. Rates of prostate biopsy and prostate cancer incidence have declined in unison, with a shift towards tumours being of higher grade and stage upon detection. Despite the recommendation, some physicians report ongoing willingness to screen appropriately selected men, and many men report intending to continue to ask for the PSA test from their physician. In the coming years, we expect to have an improved understanding of whether these decreased rates of screening will affect prostate cancer metastasis and mortality.

  5. Vitamins, metabolomics, and prostate cancer.

    PubMed

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

    2017-06-01

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

  6. Molecular imaging of prostate cancer.

    PubMed

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

    2012-07-01

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

  7. Predictive Factors and Management of Rectal Bleeding Side Effects Following Prostate Cancer Brachytherapy

    SciTech Connect

    Price, Jeremy G.; Stone, Nelson N.; Stock, Richard G.

    2013-08-01

    Purpose: To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥grade 2 proctitis. Methods and Materials: A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, and treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Results: Actuarial risk of ≥grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Conclusions: Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following

  8. Predictive factors and management of rectal bleeding side effects following prostate cancer brachytherapy.

    PubMed

    Price, Jeremy G; Stone, Nelson N; Stock, Richard G

    2013-08-01

    To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥ grade 2 proctitis. A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, and treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Actuarial risk of ≥ grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following BT. Copyright © 2013 Elsevier Inc. All rights

  9. Vaccine Treatment for Prostate Cancer

    MedlinePlus

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

  10. 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

  11. Prostate Cancer Aggressiveness Genes in Hereditary Prostate Cancer

    DTIC Science & Technology

    2006-03-01

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

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

    PubMed

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

    2016-08-01

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

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

    ERIC Educational Resources Information Center

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

    2015-01-01

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

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

    ERIC Educational Resources Information Center

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

    2015-01-01

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

  16. Urinary Biomarkers for Prostate Cancer.

    PubMed

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

    2016-02-01

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

  17. Anti-proliferative and pro-apoptotic effects of GHRH antagonists in prostate cancer

    PubMed Central

    Muñoz-Moreno, Laura; Arenas, Maria Isabel; Carmena, María J.; Schally, Andrew V.; Sánchez-Chapado, Manuel; Prieto, Juan C.; Bajo, Ana M.

    2016-01-01

    Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in the progression of various tumors. In vitro and in vivo studies have demonstrated that GHRH antagonists inhibit the growth of several cancers. GHRH antagonists, JMR-132 and JV-1-38 inhibit the growth of androgen-independent prostate tumors. Here we investigated the involvement of GHRH antagonists in proliferative and apoptotic processes. We used non-tumoral RWPE-1 and tumoral LNCaP and PC3 human prostatic epithelial cells, as well as an experimental model of human tumor PC3 cells. We evaluated the effects of JMR-132 and JV-1-38 antagonists on cell viability and proliferation in the three cell lines by means of MTT and BrdU assays, respectively, as well as on cell cycle and apoptotic process in PC3 cells. The expression levels of PCNA, p53, p21, CD44, Cyclin D1, c-myc, Bax and Bcl2 were determined in both in vivo and in vitro models by means of Western-blot and RT-PCR. GHRH antagonists suppressed cell proliferation and decreased the levels of the proliferation marker, PCNA, in the three cell lines and in PC3 tumor. GHRH antagonists led to an increase of cells in S-phase and a decrease in G1 and G2/M phases, and induced S-phase arrest and increase of apoptotic cells. The effects of GHRH-antagonists on cell cycle could be due to the changes observed in the expression of p21, p53, Bax, Bcl2, CD44, Cyclin D1, c-myc and caspase 3. Present results confirm and extend the role of GHRH antagonists as anti-proliferative and pro-apoptotic molecules in prostate cancer. PMID:27448980

  18. Challenges in Clinical Prostate Cancer: Role of Imaging

    PubMed Central

    Kelloff, Gary J.; Choyke, Peter; Coffey, Donald S.

    2010-01-01

    Objective This article reviews a recent 2-day workshop on prostate cancer and imaging technology that was conducted by the Cancer Imaging Program of the National Cancer Institute. The workshop dealt with research trends and avenues for improving imaging and applications across the clinical spectrum of the disease. Conclusion After a summary of prostate cancer incidence and mortality, four main clinical challenges in prostate cancer treatment and management—diagnostic accuracy; risk stratification, initial staging, active surveillance, and focal therapy; prostate-specific antigen relapse after radiation therapy or radical prostatectomy; and assessing response to therapy in advanced disease—were discussed by the 55-member panel. The overarching issue in prostate cancer is distinguishing lethal from nonlethal disease. New technologies and fresh uses for established procedures make imaging effective in both assessing and treating prostate cancer. PMID:19457806

  19. Prostate Cancer Screening: MedlinePlus Health Topic

    MedlinePlus

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

  20. The effect of the USPSTF PSA screening recommendation on prostate cancer incidence patterns in the USA

    PubMed Central

    Fleshner, Katherine; Carlsson, Sigrid V.; Roobol, Monique J.

    2017-01-01

    Guidelines conflict regarding recommendations for prostate-specific antigen (PSA) screening for early detection of prostate cancer. The United States Preventive Services Task Force (USPSTF) assigned a grade of D (recommending against screening) for men 75 and older in 2008 and for men of all ages in 2012. We reviewed temporal trends in rates of screening before and after the 2012 recommendation based on a literature search for studies published between 2011/01/01–2016/10/03 on PSA utilization patterns, changes in prostate cancer incidence and biopsy patterns, and how the recommendation has shaped physician and patient attitudes about PSA screening and subsequent ordering of other screening tests. Rates of PSA screening decreased by 3–10 percentage points among all age groups and within most U.S. geographic regions. Rates of prostate biopsy and prostate cancer incidence have declined in unison, with a notable shift towards higher grade, stage and risk upon detection. Despite the recommendation, some physicians reported ongoing willingness to screen appropriately selected men, and men largely reported intending to continue to ask for the PSA test. In the coming years, we expect to have a better picture of whether these decreased rates of screening will impact prostate cancer metastasis and mortality. PMID:27995937

  1. Molecular subtyping of prostate cancer.

    PubMed

    Kaffenberger, Samuel D; Barbieri, Christopher E

    2016-05-01

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

  2. Lovastatin-induced RhoA modulation and its effect on senescence in prostate cancer cells

    SciTech Connect

    Lee, Jeeyun; Lee, Inkyoung; Park, Chaehwa; Kang, Won Ki . E-mail: wkkang@smc.samsung.co.kr

    2006-01-20

    Lovastatin inhibits a 3-hydroxy 3-methylglutaryl coenzyme A reductase and prevents the synthesis of cholesterol precursors, such as farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), responsible for important cell signaling in cell proliferation and migration. Recently, the anti-cancer effect of lovastatin has been suggested in various tumor types. In this study, we showed that a low dose lovastatin induced senescence and G1 cell cycle arrest in human prostate cancer cells. Addition of GGPP or mevalonate, but not FPP, prevented the lovastatin-induced G1 phase cell cycle arrest and cell senescence. We found that constitutively active RhoA (caRhoA) reversed lovastatin-induced senescence in caRhoA-transfected PC-3 cells. Thus, we postulate that modulation of RhoA may be critical in lovastatin-induced senescence in PC-3 cells.

  3. Hormone Therapy for Prostate Cancer

    MedlinePlus

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

  4. 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

  5. Diet and survival after prostate cancer diagnosis.

    PubMed

    Berkow, Susan E; Barnard, Neal D; Saxe, Gordon A; Ankerberg-Nobis, Trulie

    2007-09-01

    Prostate cancer is the most commonly diagnosed non-skin cancer in men in the United States. Among environmental factors, diet may play a particularly important role in its incidence, progression, and clinical outcome. This article reviews the findings of eight observational studies and 17 intervention or laboratory trials on the effect of plant-based diets and plant nutrients on both the progression and clinical outcome of prostate cancer as well as additional studies examining mechanisms that may explain dietary effects. While additional long-term therapeutic clinical trials are needed to further elucidate the role of diet, these early investigations suggest that a recommendation for individual patients to shift their diets toward plant foods may serve as an important component of the tertiary treatment of prostate cancer.

  6. Lifetime implications and cost-effectiveness of using finasteride to prevent prostate cancer.

    PubMed

    Zeliadt, Steven B; Etzioni, Ruth D; Penson, David F; Thompson, Ian M; Ramsey, Scott D

    2005-08-01

    We estimate the lifetime implications of daily treatment with finasteride following the results of the Prostate Cancer Prevention Trial (PCPT). In this trial, prostate cancer prevalence was reduced by 25%; however, an increase in the number of high-grade tumors among the treatment group necessitates the long-term projection of the likely benefits and costs. We use a Markov decision analysis model with data from the trial, the SEER program, and published literature. The model measures the cost per life-year and cost per quality-adjusted life-year (QALY) gained for a cohort of men age 55 years who initiate preventive treatment with finasteride. Finasteride is associated with a gain of 6 life-years per 1000 men treated at an incremental cost of 1660000 dollars per life-year gained. The quality-adjusted analysis results in 46 QALYs gained per 1000 men treated at an incremental cost of 200000 dollars per QALY gained, due primarily to the favorable effects of finasteride on benign prostatic hyperplasia. Under the assumption that the increase in high-grade tumors observed among finasteride treated men is a pathologic artifact, the incremental costs are 290000 dollars per life-year gained and 130000 dollars per QALY gained. The cost burden associated with finasteride is substantial, while its survival benefit is small and only realized many years after initiating treatment. To achieve an incremental cost below 100000 dollars per QALY gained, the price of finasteride must be reduced by 50% from its current average wholesale price and finasteride must be shown to prevent high-grade as well as low-grade disease.

  7. 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

  8. The effect of breast cancer awareness month on internet search activity--a comparison with awareness campaigns for lung and prostate cancer.

    PubMed

    Glynn, Ronan W; Kelly, John C; Coffey, Norma; Sweeney, Karl J; Kerin, Michael J

    2011-10-12

    This work aimed to assess the effects of the annual breast cancer awareness campaign on internet search activity, and to compare these effects with those of similar campaigns in prostate and lung cancer. We further aimed to assess overall levels of online activity relating to all three neoplasms between 2004 and 2009. Google Insights for Search was employed to examine search trends for the term "breast cancer", across all Google domains between January 2004 and December 2009 (6 years). Search trends for both "prostate cancer" and "lung cancer" across all domains were also analysed for the same period, and these trends were compared with those for "breast cancer". Repeated measures ANOVA and Tukey post-hoc analyses were performed to assess for significant differences in activity. Increased levels of online activity relating to breast cancer are consistently generated each October. There is a significantly higher level of background activity in breast cancer compared with that in lung or prostate cancer (p < 0.001), and the October campaign stimulates online activity more effectively than equivalent campaigns for these other malignancies (p < 0.001). The annual breast cancer awareness campaign is proving effective in stimulating online activity and may hold useful lessons for other cancer awareness initiatives.

  9. Antineoplastic Effects of siRNA against TMPRSS2-ERG Junction Oncogene in Prostate Cancer

    PubMed Central

    Urbinati, Giorgia; Ali, Hafiz Muhammad; Rousseau, Quentin; Chapuis, Hubert; Desmaële, Didier; Couvreur, Patrick; Massaad-Massade, Liliane

    2015-01-01

    TMPRSS2-ERG junction oncogene is present in more than 50% of patients with prostate cancer and its expression is frequently associated with poor prognosis. Our aim is to achieve gene knockdown by siRNA TMPRSS2-ERG and then to assess the biological consequences of this inhibition. First, we designed siRNAs against the two TMPRSS2-ERG fusion variants (III and IV), most frequently identified in patients’ biopsies. Two of the five siRNAs tested were found to efficiently inhibit mRNA of both TMPRSS2-ERG variants and to decrease ERG protein expression. Microarray analysis further confirmed ERG inhibition by both siRNAs TMPRSS2-ERG and revealed one common down-regulated gene, ADRA2A, involved in cell proliferation and migration. The siRNA against TMPRSS2-ERG fusion variant IV showed the highest anti-proliferative effects: Significantly decreased cell viability, increased cleaved caspase-3 and inhibited a cluster of anti-apoptotic proteins. To propose a concrete therapeutic approach, siRNA TMPRSS2-ERG IV was conjugated to squalene, which can self-organize as nanoparticles in water. The nanoparticles of siRNA TMPRSS2-ERG-squalene injected intravenously in SCID mice reduced growth of VCaP xenografted tumours, inhibited oncoprotein expression and partially restored differentiation (decrease in Ki67). In conclusion, this study offers a new prospect of treatment for prostate cancer based on siRNA-squalene nanoparticles targeting TMPRSS2-ERG junction oncogene. PMID:25933120

  10. Recent advances on bisphenol-A and endocrine disruptor effects on human prostate cancer.

    PubMed

    Di Donato, Marzia; Cernera, Gustavo; Giovannelli, Pia; Galasso, Giovanni; Bilancio, Antonio; Migliaccio, Antimo; Castoria, Gabriella

    2017-12-05

    Endocrine disrupting chemicals (EDCs) are man-made substances widespread in the environment that include, among many others, bisphenol A (BPA), organochlorinated pesticides and hormone derivatives detectable in meat from animals raised in concentrated animal feeding operations. Increasing evidence indicates that EDCs have a negative impact on human health as well as on male and female fertility. They may also be associated with some endocrine diseases and increased incidence of breast and prostate cancer. This review aims to summarize available data on the (potential) impact of some common EDCs, focusing particularly on BPA, prostate cancer and their mechanisms of action. These compounds interfere with normal hormone signal pathway transduction, resulting in prolonged exposure of receptors to stimuli or interference with cellular hormone signaling in target cells. Understanding the effects of BPA and other EDCs as well as their molecular mechanism(s) may be useful in sensitizing the scientific community and the manufacturing industry to the importance of finding alternatives to their indiscriminate use. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    USDA-ARS?s Scientific Manuscript database

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

  12. Strategies for Online Organ Motion Correction for Intensity-Modulated Radiotherapy of Prostate Cancer: Prostate, Rectum, and Bladder Dose Effects

    SciTech Connect

    Rijkhorst, Erik-Jan; Lakeman, Annemarie; Nijkamp, Jasper; Bois, Josien de; Herk, Marcel van; Lebesque, Joos V.; Sonke, Jan-Jakob

    2009-11-15

    Purpose: To quantify and evaluate the accumulated prostate, rectum, and bladder dose for several strategies including rotational organ motion correction for intensity-modulated radiotherapy (IMRT) of prostate cancer using realistic organ motion data. Methods and Materials: Repeat computed tomography (CT) scans of 19 prostate patients were used. Per patient, two IMRT plans with different uniform margins were created. To quantify prostate and seminal vesicle motion, repeat CT clinical target volumes (CTVs) were matched onto the planning CTV using deformable registration. Four different strategies, from online setup to full motion correction, were simulated. Rotations were corrected for using gantry and collimator angle adjustments. Prostate, rectum, and bladder doses were accumulated for each patient, plan, and strategy. Minimum CTV dose (D{sub min}), rectum equivalent uniform dose (EUD, n = 0.13), and bladder surface receiving >=78 Gy (S78), were calculated. Results: With online CTV translation correction, a 7-mm margin was sufficient (i.e., D{sub min} >= 95% of the prescribed dose for all patients). A 4-mm margin required additional rotational correction. Margin reduction lowered the rectum EUD(n = 0.13) by approx2.6 Gy, and the bladder S78 by approx1.9%. Conclusions: With online correction of both translations and rotations, a 4-mm margin was sufficient for 15 of 19 patients, whereas the remaining four patients had an underdosed CTV volume <1%. Margin reduction combined with online corrections resulted in a similar or lower dose to the rectum and bladder. The more advanced the correction strategy, the better the planned and accumulated dose agreed.

  13. Cytotoxic Effects of the Ethanol Bane Skin Extract in Human Prostate Cancer Pc3 Cells

    PubMed Central

    Amiri, Maryam; Kazerouni, Faranak; Namaki, Saeed; Darbandi Tamijani, Hassan; Rahimipour, Hooman; Boroumand, Nasrin; Barghi, Siyamak; Ebrahimi, Nazanin; Gheibi Hayat, Seyed Mohammad

    2016-01-01

    Background: It is extensively supposed that vegetarian diet could affect cancer progress and increase the influence of formal chemotherapy. Objectives: The present study was designed to determine the effect of the ethanol Bane skin extract against chemo resistant prostate cancer PC3 cells. Materials and Methods: PC3 and L929 cells were cultivated and then incubated in the ethanol Bane skin extract with various concentrations of 0.78, 1.5, 3.13, 6.25, 12.5 mg/mL in 3 times 24, 48, 72 hours. Cytotoxic effect of the ethanol Bane skin extract on PC3 and L929 cells was examined by MTT assay after 24, 48, and 72 hours. Morphology of PC3 cells was evaluated by Gimsa staining. Results: The ethanol Bane skin extract inhibited proliferation and caused cell death with IC50 values of 2.8 mg/mL on PC3 cells and the IC50 was 6.1 mg/mL on l929 cells. Morphological changes and apoptotic bodies were observed in PC3 cells faced with the ethanol Bane skin extract by staining with Gimsa. Conclusions: The ethanol Bane skin extract could repress the growth of PC3 cell line. This inhibitory effect of the Bane extract depended on the dose and the time on PC3. The result of this study shows that the ethanol Bane skin extract includes photochemical and inhibitory function against proliferation and inducer of apoptosis in human prostate cancer PC3 cells and also has less cytotoxic effect on l929 than PC3 cells. The ethanol Bane skin extract might be a good candidate for the new herbal anticancer drug. PMID:27482333

  14. Molecular Imaging of Prostate Cancer

    PubMed Central

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

    2015-01-01

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

  15. Prostate Cancer Clinical Consortium Clinical Research Site:Targeted Therapies

    DTIC Science & Technology

    2015-10-01

    Cornell Medical College Prostate Cancer Research Program (WCMC-PCRP) is a Clinical Research Site of the Prostate Cancer Clinical Trials Consortium...effectively bring novel agents and new biomarker driven trials directly to patients 17 Table of Contents Page 1. Introduction...purpose and scope of the research. The Weill Cornell Medical College Prostate Cancer Research Program (WCMC-PCRP) is a Clinical Research Site of the

  16. CK2 abrogates the inhibitory effects of PRH/HHEX on prostate cancer cell migration and invasion and acts through PRH to control cell proliferation

    PubMed Central

    Siddiqui, Y H; Kershaw, R M; Humphreys, E H; Assis Junior, E M; Chaudhri, S; Jayaraman, P-S; Gaston, K

    2017-01-01

    PRH/HHEX (proline-rich homeodomain protein/haematopoietically expressed homeobox protein) is a transcription factor that controls cell proliferation, cell differentiation and cell migration. Our previous work has shown that in haematopoietic cells, Protein Kinase CK2-dependent phosphorylation of PRH results in the inhibition of PRH DNA-binding activity, increased cleavage of PRH by the proteasome and the misregulation of PRH target genes. Here we show that PRH and hyper-phosphorylated PRH are present in normal prostate epithelial cells, and that hyper-phosphorylated PRH levels are elevated in benign prostatic hyperplasia, prostatic adenocarcinoma, and prostate cancer cell lines. A reduction in PRH protein levels increases the motility of normal prostate epithelial cells and conversely, PRH over-expression inhibits prostate cancer cell migration and blocks the ability of these cells to invade an extracellular matrix. We show that CK2 over-expression blocks the repression of prostate cancer cell migration and invasion by PRH. In addition, we show that PRH knockdown in normal immortalised prostate cells results in an increase in the population of cells capable of colony formation in Matrigel, as well as increased cell invasion and decreased E-cadherin expression. Inhibition of CK2 reduces PRH phosphorylation and reduces prostate cell proliferation but the effects of CK2 inhibition on cell proliferation are abrogated in PRH knockdown cells. These data suggest that the increased phosphorylation of PRH in prostate cancer cells increases both cell proliferation and tumour cell migration/invasion. PMID:28134934

  17. [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.

  18. 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

  19. Molecular Effects of 13C/DIM in Prostate Cancer

    DTIC Science & Technology

    2006-04-01

    cells.50 Sierens et al.51 have found that isoflavone supplementation reduces hydrogen peroxide -induced DNA damage in sperm, suggesting the antioxidant...tetradecanoylphorbol-13-acetate induced hydrogen peroxide production in human polymorphonuclear leukocytes and HL-60 cells, sug- gesting the inhibitory effect...inhibits lipid peroxidation in rat brain, liver, and lens, suggesting its antiox- idant properties.78–80 Chuang et al.81 have shown that curcumin inhibits

  20. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

    DTIC Science & Technology

    2016-12-01

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

  1. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

    DTIC Science & Technology

    2016-11-01

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

  2. Anticancer properties of carotenoids in prostate cancer. A review.

    PubMed

    Soares, Nathalia da Costa Pereira; Teodoro, Anderson Junger; Lotsch, Priscila Falagan; Granjeiro, José Mauro; Borojevic, Radovan

    2015-10-01

    Prostate cancer is the most common noncutaneous cancer of men in the world. Several epidemiological studies have linked increased carotenoids consumption with decreased prostate cancer risk. These findings are supported by in vitro and in vivo experiments showing that carotenoids not only enhance the antioxidant response of prostate cells, but that they are able to inhibit proliferation, induce apoptosis and decrease the metastatic capacity of prostate cancer cells. However, clear clinical evidence supporting the use of carotenoids in prevention or treatment of prostate cancer is not available, due to the limited number of published randomized clinical trials, and the varying protocols used in the existing studies. The scope of the present review is to discuss the potential impact of carotenoids on prostate cancer by giving an overview of the molecular mechanisms and in vitro / in vivo effects.

  3. Adenovirus-derived vectors for prostate cancer gene therapy.

    PubMed

    de Vrij, Jeroen; Willemsen, Ralph A; Lindholm, Leif; Hoeben, Rob C; Bangma, Chris H; Barber, Chris; Behr, Jean-Paul; Briggs, Simon; Carlisle, Robert; Cheng, Wing-Shing; Dautzenberg, Iris J C; de Ridder, Corrina; Dzojic, Helena; Erbacher, Patrick; Essand, Magnus; Fisher, Kerry; Frazier, April; Georgopoulos, Lindsay J; Jennings, Ian; Kochanek, Stefan; Koppers-Lalic, Daniela; Kraaij, Robert; Kreppel, Florian; Magnusson, Maria; Maitland, Norman; Neuberg, Patrick; Nugent, Regina; Ogris, Manfred; Remy, Jean-Serge; Scaife, Michelle; Schenk-Braat, Ellen; Schooten, Erik; Seymour, Len; Slade, Michael; Szyjanowicz, Pio; Totterman, Thomas; Uil, Taco G; Ulbrich, Karel; van der Weel, Laura; van Weerden, Wytske; Wagner, Ernst; Zuber, Guy

    2010-07-01

    Prostate cancer is a leading cause of death among men in Western countries. Whereas the survival rate approaches 100% for patients with localized cancer, the results of treatment in patients with metastasized prostate cancer at diagnosis are much less successful. The patients are usually presented with a variety of treatment options, but therapeutic interventions in prostate cancer are associated with frequent adverse side effects. Gene therapy and oncolytic virus therapy may constitute new strategies. Already a wide variety of preclinical studies has demonstrated the therapeutic potential of such approaches, with oncolytic prostate-specific adenoviruses as the most prominent vector. The state of the art and future prospects of gene therapy in prostate cancer are reviewed, with a focus on adenoviral vectors. We summarize advances in adenovirus technology for prostate cancer treatment and highlight areas where further developments are necessary.

  4. Methylseleninic acid enhances the effect of etoposide to inhibit prostate cancer growth in vivo.

    PubMed

    Gonzalez-Moreno, Oscar; Segura, Victor; Serrano, Diego; Nguewa, Paul; de las Rivas, Javier; Calvo, Alfonso

    2007-09-15

    New therapeutic agents are needed for the treatment of androgen-independent prostate cancer (PrCa). We have investigated the effect of methylseleninic acid (MSA) on tumor stage-specific prostate cells derived from the C3 (1)/Tag model for PrCa: Pr111, a slow-growing and nontumorigenic cell line isolated from a prostate intraepithelial neoplasia lesion; Pr14, a tumorigenic line derived from a primary tumor; and Pr14C1, a sub-clone of Pr14 explanted from a lung metastasis. We demonstrate that MSA strongly inhibits cell growth and induces apoptosis in C3 (1)/Tag tumor cells, in a dose-dependent manner. A decrease in phosphorylated ERK1/2 and AKT was also found in tumor cells, but not in Pr111. Microarray analysis using affymetrix showed that the number of genes with an altered expression in tumor cells is significantly higher (p < 0.01) than in nontumoral cells. Pathways analyses revealed a decrease in the expression of genes involved in metabolism (Fabp5, Cyba), signal transduction (ERK, AKT), angiogenesis (neuropilin-1, Flt-4) and transcription (cAMP response element-binding protein) in tumor cells. The expression of neuropilin-1, a protein involved in VEGF signaling and tumor angiogenesis, was 97-fold repressed in Pr14 cells treated with MSA. Combination treatments using low doses of etoposide or taxotere (docetaxel), plus low doses of MSA revealed a strong enhancement of cell growth inhibition and apoptosis in tumor cells. Our in vivo studies using Pr14 cells xenografted into nude mice demonstrated that MSA significantly enhances the chemotherapeutical effect of etoposide, resulting in 78.3% tumor growth inhibition. These results suggest that MSA could be used against PrCa to enhance the effect of etoposide. (c) 2007 Wiley-Liss, Inc.

  5. Effect of Family History on Outcomes in Patients Treated With Definitive Brachytherapy for Clinically Localized Prostate Cancer

    SciTech Connect

    Peters, Christopher A. Stock, Richard G.; Blacksburg, Seth R.; Stone, Nelson N.

    2009-01-01

    Purpose: To determine the impact familial prostate cancer has on prognosis in men treated with brachytherapy for clinically localized prostate cancer. Methods and Materials: A total of 1,738 consecutive patients with prostate cancer (cT1-3, N0/X, M0) received low-dose-rate brachytherapy alone or in combination with external beam radiation therapy or hormone ablation from 1992 to 2005. The primary end-point was freedom from biochemical failure (FFBF) using the Phoenix definition. Minimum follow-up was 2 years and the median follow-up was 60 months (range, 24-197 months). Results: A total of 187 of 1,738 men (11%) had a family history of prostate cancer in a first-degree relative. For the low-risk patients, both groups had similar actuarial 5-year FFBF (97.2% vs. 95.5%, p = 0.516). For intermediate-risk patients, there was a trend toward improved biochemical control in men positive for family history (5-yr FFBF 100% vs. 93.6%, p = 0.076). For the high-risk patients, men with a positive family history had similar 5-year FFBF (92.8% vs. 85.2%, p = 0.124). On multivariate analysis, family history was not significant; use of hormones, high biologic effective dose, initial prostate-specific antigen value, and Gleason score were the significant variables predicting biochemical control. Conclusions: This is the first study to examine the relationship of familial prostate cancer and outcomed in men treated with brachytherapy alone or in combination therapy. Men with a positive family history have clinicopathologic characteristics and biochemical outcomes similar to those with sporadic disease.

  6. Effect of family history on outcomes in patients treated with definitive brachytherapy for clinically localized prostate cancer.

    PubMed

    Peters, Christopher A; Stock, Richard G; Blacksburg, Seth R; Stone, Nelson N

    2009-01-01

    To determine the impact familial prostate cancer has on prognosis in men treated with brachytherapy for clinically localized prostate cancer. A total of 1,738 consecutive patients with prostate cancer (cT1-3, N0/X, M0) received low-dose-rate brachytherapy alone or in combination with external beam radiation therapy or hormone ablation from 1992 to 2005. The primary end-point was freedom from biochemical failure (FFBF) using the Phoenix definition. Minimum follow-up was 2 years and the median follow-up was 60 months (range, 24-197 months). A total of 187 of 1,738 men (11%) had a family history of prostate cancer in a first-degree relative. For the low-risk patients, both groups had similar actuarial 5-year FFBF (97.2% vs. 95.5%, p = 0.516). For intermediate-risk patients, there was a trend toward improved biochemical control in men positive for family history (5-yr FFBF 100% vs. 93.6%, p = 0.076). For the high-risk patients, men with a positive family history had similar 5-year FFBF (92.8% vs. 85.2%, p = 0.124). On multivariate analysis, family history was not significant; use of hormones, high biologic effective dose, initial prostate-specific antigen value, and Gleason score were the significant variables predicting biochemical control. This is the first study to examine the relationship of familial prostate cancer and outcomed in men treated with brachytherapy alone or in combination therapy. Men with a positive family history have clinicopathologic characteristics and biochemical outcomes similar to those with sporadic disease.

  7. Prostate cancer: endogenous chemical castration.

    PubMed

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

    2016-04-28

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

  8. Chemopreventive Effects of Tea in Prostate Cancer: Green Tea vs. Black Tea

    PubMed Central

    Henning, Susanne M.; Wang, Piwen; Heber, David

    2011-01-01

    The polyphenol compositions of green tea (GT) and black tea (BT) are very different due to post-harvest processing. GT contains higher concentrations of monomeric polyphenols, which affect numerous intracellular signaling pathways involved in prostate cancer (CaP) development. BT polymers, on the other hand, are poorly absorbed and are converted to phenolic acids by the colonic microflora. Therefore, after consumption of GT higher concentrations of polyphenols are found in the circulation while after BT consumption the phenolic acid levels in the circulation are higher. The majority of in vitro cell culture, in vivo animal, and clinical intervention studies examine the effects of extracts of GT or purified (-)-epigallocatechin-3-gallate (EGCG) on prostate carcinogenesis. These studies provide strong evidence supporting a chemopreventive effect of GT, but results from epidemiological studies of GT consumption are mixed. While the evidence for a chemopreventive effect of BT is much weaker than the body of evidence with regard to GT, there are several animal BT intervention studies demonstrating inhibition of CaP growth. This article will review in detail the available epidemiological and human clinical studies, as well as animal and basic mechanistic studies on GT and BT supporting a chemopreventive role in CaP. PMID:21538852

  9. Inhibition of CHOP accentuates the apoptotic effect of α-mangostin from the mangosteen fruit (Garcinia mangostana) in 22Rv1 prostate cancer cells.

    PubMed

    Li, Gongbo; Petiwala, Sakina M; Nonn, Larisa; Johnson, Jeremy J

    2014-10-10

    The mangosteen (Garcinia mangostana) fruit has been a popular food in Southeast Asia for centuries and is increasing in popularity in Western countries. We identified α-Mangostin as a primary phytochemical modulating ER stress proteins in prostate cancer cells and propose that α-Mangostin is responsible for exerting a biological effect in prostate cancer cells. Two human prostate cancer cell lines, 22Rv1 and LNCaP, and prostate epithelial cells procured from two patients undergoing radical prostatectomy were treated with α-Mangostin and evaluated by RT-PCR, Western blot, fluorescent microscopy and siRNA transfection to evaluate ER stress. Next, we evaluated α-Mangostin for microsomal stability, pharmacokinetic parameters, and anti-cancer activity in nude mice. α-Mangostin significantly upregulated ER stress markers in prostate cancer cells. Interestingly, α-Mangostin did not promote ER stress in prostate epithelial cells (PrECs) from prostate cancer patients. CHOP knockdown enhanced α-Mangostin-induced apoptosis in prostate cancer cells. α-Mangostin significantly suppressed tumor growth in a xenograft tumor model without obvious toxicity. Our study suggests that α-Mangostin is not the only active constituent from the mangosteen fruit requiring further work to understand the complex chemical composition of the mangosteen. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Precise preoperative localization of prostate cancer employing 12-core needle biopsy with a tissue-marking method for effective surgical strategy.

    PubMed

    Sato, Satoko; Watanabe, Mika; Taniuchi, Shinji; Kasajima, Atsuko; Mitsuzuka, Koji; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Arai, Yoichi; Sasano, Hironobu

    2015-05-01

    Prostate needle biopsy plays a pivotal role not only in the diagnosis but also the management of patients with prostate cancer. Prostate cancer is often multifocal and diagnosis of the lesion could therefore be difficult with diagnostic imaging only; thus, multiple core biopsies are taken from several different regions of the prostate. In current practice, 10- or 12-core needle biopsy is considered the clinical standard. Several techniques have been reported to improve the orientation of the specimens, but tissue marking, which could theoretically provide important information on the location of the lesion in the prostate, has been rarely reported. Therefore, in this study, we evaluated the clinical significance of systematic 12-core needle biopsy with tissue marking for preoperative prediction of lesion sites and clinicopathological features of patients. We evaluated 93 patients who underwent 12-core prostate biopsy and subsequent radical prostatectomy. We correlated the biopsy results to the prostate sites in which biopsies were performed and prognostic factors of the patients, especially the degree of extraprostatic extension (EPE) obtained in surgical specimens. Among 253 cancer foci detected in 93 prostatectomy specimens, 168 (66.4%) foci were detected by biopsy. All patients had proven cancer. EPE-positive cancers were associated with a larger number of positive cores, larger tumor length, and higher percentage of cancer tissue in the corresponding cores. Systematic 12-core prostate biopsy with tissue marking is useful for preoperative detection of cancer foci and provides valuable information that enables effective surgical strategies.

  11. 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

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

    PubMed

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

    2014-06-01

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

  13. 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

  14. [The epidemiology of prostate cancer].

    PubMed

    Rébillard, Xavier; Tretarre, Brigitte; Villers, Arnauld

    2003-12-31

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

  15. Heterogeneous patterns of DNA methylation-based field effects in histologically normal prostate tissue from cancer patients

    PubMed Central

    Møller, Mia; Strand, Siri Hundtofte; Mundbjerg, Kamilla; Liang, Gangning; Gill, Inderbir; Haldrup, Christa; Borre, Michael; Høyer, Søren; Ørntoft, Torben Falck; Sørensen, Karina Dalsgaard

    2017-01-01

    Prostate cancer (PC) diagnosis is based on histological evaluation of prostate needle biopsies, which have high false negative rates. Here, we investigated if cancer-associated epigenetic field effects in histologically normal prostate tissue may be used to increase sensitivity for PC. We focused on nine genes (AOX1, CCDC181 (C1orf114), GABRE, GAS6, HAPLN3, KLF8, MOB3B, SLC18A2, and GSTP1) known to be hypermethylated in PC. Using quantitative methylation-specific PCR, we analysed 66 malignant and 134 non-malignant tissue samples from 107 patients, who underwent ultrasound-guided prostate biopsy (67 patients had at least one cancer-positive biopsy, 40 had exclusively cancer-negative biopsies). Hypermethylation was detectable for all genes in malignant needle biopsy samples (AUC: 0.80 to 0.98), confirming previous findings in prostatectomy specimens. Furthermore, we identified a four-gene methylation signature (AOX1xGSTP1xHAPLN3xSLC18A2) that distinguished histologically non-malignant biopsies from patients with vs. without PC in other biopsies (AUC = 0.65; sensitivity = 30.8%; specificity = 100%). This signature was validated in an independent patient set (59 PC, 36 adjacent non-malignant, and 9 normal prostate tissue samples) analysed on Illumina 450 K methylation arrays (AUC = 0.70; sensitivity = 40.6%; specificity = 100%). Our results suggest that a novel four-gene signature may be used to increase sensitivity for PC diagnosis through detection of epigenetic field effects in histologically non-malignant prostate tissue samples. PMID:28084441

  16. Heterogeneous patterns of DNA methylation-based field effects in histologically normal prostate tissue from cancer patients.

    PubMed

    Møller, Mia; Strand, Siri Hundtofte; Mundbjerg, Kamilla; Liang, Gangning; Gill, Inderbir; Haldrup, Christa; Borre, Michael; Høyer, Søren; Ørntoft, Torben Falck; Sørensen, Karina Dalsgaard

    2017-01-13

    Prostate cancer (PC) diagnosis is based on histological evaluation of prostate needle biopsies, which have high false negative rates. Here, we investigated if cancer-associated epigenetic field effects in histologically normal prostate tissue may be used to increase sensitivity for PC. We focused on nine genes (AOX1, CCDC181 (C1orf114), GABRE, GAS6, HAPLN3, KLF8, MOB3B, SLC18A2, and GSTP1) known to be hypermethylated in PC. Using quantitative methylation-specific PCR, we analysed 66 malignant and 134 non-malignant tissue samples from 107 patients, who underwent ultrasound-guided prostate biopsy (67 patients had at least one cancer-positive biopsy, 40 had exclusively cancer-negative biopsies). Hypermethylation was detectable for all genes in malignant needle biopsy samples (AUC: 0.80 to 0.98), confirming previous findings in prostatectomy specimens. Furthermore, we identified a four-gene methylation signature (AOX1xGSTP1xHAPLN3xSLC18A2) that distinguished histologically non-malignant biopsies from patients with vs. without PC in other biopsies (AUC = 0.65; sensitivity = 30.8%; specificity = 100%). This signature was validated in an independent patient set (59 PC, 36 adjacent non-malignant, and 9 normal prostate tissue samples) analysed on Illumina 450 K methylation arrays (AUC = 0.70; sensitivity = 40.6%; specificity = 100%). Our results suggest that a novel four-gene signature may be used to increase sensitivity for PC diagnosis through detection of epigenetic field effects in histologically non-malignant prostate tissue samples.

  17. Prostate Cancer: Symptoms, Tests, and Treatment

    MedlinePlus

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

  18. Metabolic Risk Factors in Prostate Cancer

    PubMed Central

    Chu, David I.; Freedland, Stephen J.

    2010-01-01

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

  19. Effects of Family History and Genetic Polymorphism on the Cost-Effectiveness of Chemoprevention With Finasteride for Prostate Cancer

    PubMed Central

    Reed, Shelby D.; Scales, Charles D.; Stewart, Suzanne B.; Sun, Jielin; Moul, Judd W.; Schulman, Kevin A.; Xu, Jianfeng

    2010-01-01

    Purpose Improvement in the cost-effectiveness of chemoprevention for prostate cancer could be realized through the identification of patients at higher risk. We estimated the cost-effectiveness of prostate cancer chemoprevention across risk groups defined by family history and number of risk alleles and the cost-effectiveness of targeting chemoprevention to higher-risk groups. Materials and Methods We developed a probabilistic Markov model to estimate costs, survival, and quality-adjusted survival across risk groups for patients receiving or not receiving chemoprevention with finasteride. The model uses data from national cancer registries, online sources, and the medical literature. Results The incremental cost-effectiveness of 25 years of chemoprevention with finasteride in patients aged 50 years was an estimated $89,300 per quality-adjusted life-year (95% confidence interval, $58,800-$149,800), assuming finasteride reduced all grades of prostate cancer by 24.8%. Among patients with positive family history (without genetic testing), chemoprevention provided 1 additional QALY at a cost of $64,200. Among patients with negative family history, at $400 per person tested, the cost-effectiveness of genetically targeted chemoprevention ranged from $98,100 per QALY when limiting finasteride to patients with 14 or more risk alleles to $103,200 per QALY when including patients with 8 or more risk alleles. Conclusions Although there are small differences in the cost-effectiveness of genetically targeted chemoprevention strategies in patients with negative family history, genetic testing could reduce total expenditures if used to target chemoprevention for higher-risk groups. PMID:21239023

  20. Effects of family history and genetic polymorphism on the cost-effectiveness of chemoprevention with finasteride for prostate cancer.

    PubMed

    Reed, Shelby D; Scales, Charles D; Stewart, Suzanne B; Sun, Jielin; Moul, Judd W; Schulman, Kevin A; Xu, Jianfeng

    2011-03-01

    Improvement in the cost-effectiveness of chemoprevention for prostate cancer could be realized through the identification of patients at higher risk. We estimated the cost-effectiveness of prostate cancer chemoprevention across risk groups defined by family history and number of risk alleles, and the cost-effectiveness of targeting chemoprevention to higher risk groups. We developed a probabilistic Markov model to estimate costs, survival and quality adjusted survival across risk groups for patients receiving or not receiving chemoprevention with finasteride. The model uses data from national cancer registries, online sources and the medical literature. The incremental cost-effectiveness of 25 years of chemoprevention with finasteride in patients 50 years old was an estimated $89,300 per quality adjusted life-year (95% CI $58,800-$149,800), assuming finasteride decreased all grades of prostate cancer by 24.8%. Among patients with a positive family history (without genetic testing) chemoprevention provided 1 additional quality adjusted life-year at a cost of $64,200. Among patients with a negative family history at $400 per person tested, the cost-effectiveness of genetically targeted chemoprevention ranged from $98,100 per quality adjusted life-year when limiting finasteride to individuals with 14 or more risk alleles, to $103,200 per quality adjusted life-year when including those with 8 or more risk alleles. Although there are small differences in the cost-effectiveness of genetically targeted chemoprevention strategies in patients with a negative family history, genetic testing could reduce total expenditures if used to target chemoprevention for higher risk groups. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  1. Diet, Supplement Use, and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial

    PubMed Central

    Kristal, Alan R.; Arnold, Kathryn B.; Neuhouser, Marian L.; Goodman, Phyllis; Platz, Elizabeth A.; Albanes, Demetrius; Thompson, Ian M.

    2010-01-01

    The authors examined nutritional risk factors for prostate cancer among 9,559 participants in the Prostate Cancer Prevention Trial (United States and Canada, 1994–2003). The presence or absence of cancer was determined by prostate biopsy, which was recommended during the trial because of an elevated prostate-specific antigen level or an abnormal digital rectal examination and was offered to all men at the trial's end. Nutrient intake was assessed using a food frequency questionnaire and a structured supplement-use questionnaire. Cancer was detected in 1,703 men; 127 cancers were high-grade (Gleason score 8–10). There were no associations of any nutrient or supplement with prostate cancer risk overall. Risk of high-grade cancer was associated with high intake of polyunsaturated fats (quartile 4 vs. quartile 1: odds ratio = 2.41, 95% confidence interval (CI): 1.33, 4.38). Dietary calcium was positively associated with low-grade cancer but inversely associated with high-grade cancer (for quartile 4 vs. quartile 1, odds ratios were 1.27 (95% CI: 1.02, 1.57) and 0.43 (95% CI: 0.21, 0.89), respectively). Neither dietary nor supplemental intakes of nutrients often suggested for prostate cancer prevention, including lycopene, long-chain n-3 fatty acids, vitamin D, vitamin E, and selenium, were significantly associated with cancer risk. High intake of n-6 fatty acids, through their effects on inflammation and oxidative stress, may increase prostate cancer risk. PMID:20693267

  2. The effects of motion on the dose distribution of proton radiotherapy for prostate cancer.

    PubMed

    Qamhiyeh, Sima; Geismar, Dirk; Pöttgen, Christoph; Stuschke, Martin; Farr, Jonathan

    2012-05-10

    Proton radiotherapy of the prostate basal or whole seminal vesicles using scattering delivery systems is an effective treatment of prostate cancer that has been evaluated in prospective trials. Meanwhile, the use of pencil beam scanning (PBS) can further reduce the dose in the beam entrance channels and reduce the dose to the normal tissues. However, PBS dose distributions can be affected by intra- and interfractional motion. In this treatment planning study, the effects of intra- and interfractional organ motion on PBS dose distributions are investigated using repeated CT scans at close and distant time intervals. The minimum dose (Dmin) and the dose to 2% and 98% of the volumes (D2% and D98%), as well as EUD in the clinical target volumes (CTV), is used as measure of robustness. In all patients, D98% was larger than 96% and D2% was less than 106% of the prescribed dose. The combined information from Dmin, D98% and EUD led to the conclusion that there are no relevant cold spots observed in any of the verification plans. Moreover, it was found that results of single field optimization are more robust than results from multiple field optimizations.

  3. Enoxacin inhibits growth of prostate cancer cells and effectively restores microRNA processing

    PubMed Central

    Sousa, Elsa J.; Graça, Inês; Baptista, Tiago; Vieira, Filipa Q.; Palmeira, Carlos; Henrique, Rui; Jerónimo, Carmen

    2013-01-01

    Prostate cancer (PCa) is one of the most incident malignancies worldwide. Although efficient therapy is available for early-stage PCa, treatment of advanced disease is mainly ineffective and remains a clinical challenge. microRNA (miRNA) dysregulation is associated with PCa development and progression. In fact, several studies have reported a widespread downregulation of miRNAs in PCa, which highlights the importance of studying compounds capable of restoring the global miRNA expression. The main aim of this study was to define the usefulness of enoxacin as an anti-tumoral agent in PCa, due to its ability to induce miRNA biogenesis in a TRBP-mediated manner. Using a panel of five PCa cell lines, we observed that all of them were wild type for the TARBP2 gene and expressed TRBP protein. Furthermore, primary prostate carcinomas displayed normal levels of TRBP protein. Remarkably, enoxacin was able to decrease cell viability, induce apoptosis, cause cell cycle arrest, and inhibit the invasiveness of cell lines. Enoxacin was also effective in restoring the global expression of miRNAs. This study is the first to show that PCa cells are highly responsive to the anti-tumoral effects of enoxacin. Therefore, enoxacin constitutes a promising therapeutic agent for PCa. PMID:23644875

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

    PubMed

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

    2011-03-01

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

  5. Prostate Cancer Genetics: Variation by Race, Ethnicity, and Geography.

    PubMed

    Rebbeck, Timothy R

    2017-01-01

    Prostate cancer rates vary substantially by race, ethnicity, and geography. These disparities can be explained by variation in access to screening and treatment, variation in exposure to prostate cancer risk factors, and variation in the underlying biology of prostate carcinogenesis (including genomic propensity of some groups to develop biologically aggressive disease). It is clear that access to screening and access to treatment are critical influencing factors of prostate cancer rates; yet, even among geographically diverse populations with similar access to care (eg, low- and medium-income countries), African descent men have higher prostate cancer rates and poorer prognosis. To date, the proportion of prostate cancer that can be explained by environmental exposures is small, and the effect of these factors across different racial, ethnic, or geographical populations is poorly understood. In contrast, prostate cancer has one of the highest heritabilities of all major cancers. Numerous genetic susceptibility markers have been identified from family-based studies, candidate gene association studies, and genome-wide association studies. Some prostate cancer loci, including the risk loci found at chromosome 8q24, have consistent effects in all groups studied to date. However, replication of many susceptibility loci across race, ethnicity, and geography remains limited, and additional studies in certain populations (particularly in men of African descent) are needed to better understand the underlying genetic basis of prostate cancer.

  6. Effect of D-allose on prostate cancer cell lines: phospholipid profiling by nanoflow liquid chromatography-tandem mass spectrometry.

    PubMed

    Jeong, Rae Ung; Lim, Sangsoo; Kim, Myoung Ok; Moon, Myeong Hee

    2011-08-01

    D-Allose, a rare, naturally occurring monosaccharide, is known to exert anti-proliferative effects on cancer cells. The effects of D-allose on the cellular membranes of hormone-refractory prostate cancer cell line (DU145), hormone-sensitive prostate cancer cell line (LNCaP), and normal prostate epithelial cells (PrEC) were studied at the molecular level by phospholipid (PL) profiling using a shotgun lipidomic method. The molecular structures of 85 PL species including 23 phosphatidylcholines, 12 phosphatidylethanolamines (PEs), 11 phosphatidylserines (PSs), 16 phosphatidylinositols, 9 phosphatidic acids (PAs), and 14 phosphatidylglycerols (PGs) were identified by data-dependent collision-induced dissociation of nanoflow liquid chromatography-tandem mass spectrometry, and the PL amounts were quantified. The addition of D-allose to prostate cancer cell lines during their growth phases had negligible or decreased effects on the relative regulation of PL species, but several new PS molecules (two for DU145 and three for LNCaP) emerged. In contrast, experiments on the PrEC cell line revealed that some high abundant species (14:0/14:0-PE, 16:2/16:0-PG, and 20:6/18:1-PA) showed significant increases in concentration. These findings support a mechanism for the anti-proliferative effect of D-allose on prostate cancer cell lines that involves the induction of programmed cell death since PS molecules are known to induce apoptosis. Principal component analysis was carried out to examine differences in PL distributions among the three cell lines promoted by D-allose.

  7. [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.

  8. Do Prostate Cancer Exosomes Generate a Field Effect Leading to Tumor Multifocality

    DTIC Science & Technology

    2016-04-01

    Nakai Y, Isaacs WB and Nelson WG: Inflammation in prostate carcinogenesis. Nat Rev Cancer 7: 256-269, 2007. 4. De Marzo AM, Marchi VL, Epstein JI and...Saturation biopsies for prostate cancer: current uses and future prospects. Nat Rev Urol 6: 645-652, 2009. 19. Eichler K, Hempel S, Wilby J, Myers L...PERSON USAMRMC a. REPORT U b. ABSTRACT U c. THIS PAGE U UU 38 19b. TELEPHONE NUMBER (include area code) Standard Form 298 ( Rev . 8-98

  9. The Effect of Finasteride and Dutasteride on the Growth of WPE1-NA22 Prostate Cancer Xenografts in Nude Mice

    PubMed Central

    Opoku-Acheampong, Alexander B.; Nelsen, Michelle K.; Unis, Dave; Lindshield, Brian L.

    2012-01-01

    Background 5α-reductase 1 (5αR1) and 5α-reductase 2 (5αR2) convert testosterone into the more potent androgen dihydrotestosterone. 5αR2 is the main isoenzyme in normal prostate tissue; however, most prostate tumors have increased 5αR1 and decreased 5αR2 expression. Previously, finasteride (5αR2 inhibitor) treatment begun 3 weeks post-tumor implantation had no effect on Dunning R3327-H rat prostate tumor growth. We believe the tumor compensated for finasteride treatment by increasing tumor 5αR1 expression or activity. We hypothesize that finasteride treatment would not significantly alter tumor growth even if begun before tumor implantation, whereas dutasteride (5αR1 and 5αR2 inhibitor) treatment would decrease tumor growth regardless of whether treatment was initiated before or after tumor implantation. Methodology/Principal Findings Sixty 8-week-old male nude mice were randomized to Control, Pre- and Post-Finasteride, and Pre- and Post-Dutasteride (83.3 mg drug/kg diet) diet groups. Pre- and post-groups began their treatment diets 1–2 weeks prior to or 3 weeks after subcutaneous injection of 1×105 WPE1-NA22 human prostate cancer cells, respectively. Tumors were allowed to grow for 22 weeks; tumor areas, body weights, and food intakes were measured weekly. At study's conclusion, prostate and seminal vesicle weights were significantly decreased in all treatment groups versus the control; dutasteride intake significantly decreased seminal vesicle weights compared to finasteride intake. No differences were measured in final tumor areas or tumor weights between groups, likely due to poor tumor growth. In follow-up studies, proliferation of WPE1-NA22 prostate cancer cells and parent line RWPE-1 prostate epithelial cells were unaltered by treatment with testosterone, dihydrotestosterone, or mibolerone, suggesting that these cell lines are not androgen-sensitive. Conclusion The lack of response of WPE1-NA22 prostate cancer cells to androgen treatment may

  10. Differential Effects of Tissue Culture Coating Substrates on Prostate Cancer Cell Adherence, Morphology and Behavior

    PubMed Central

    Liberio, Michelle S.; Sadowski, Martin C.; Soekmadji, Carolina; Davis, Rohan A.; Nelson, Colleen C.

    2014-01-01

    Weak cell-surface adhesion of cell lines to tissue culture surfaces is a common problem and presents technical limitations to the design of experiments. To overcome this problem, various surface coating protocols have been developed. However, a comparative and precise real-time measurement of their impact on cell behavior has not been conducted. The prostate cancer cell line LNCaP, derived from a patient lymph node metastasis, is a commonly used model system in prostate cancer research. However, the cells’ characteristically weak attachment to the surface of tissue culture vessels and cover slips has impeded their manipulation and analysis and use in high throughput screening. To improve the adherence of LNCaP cells to the culture surface, we compared different coating reagents (poly-l-lysine, poly-l-ornithine, collagen type IV, fibronectin, and laminin) and culturing conditions and analyzed their impact on cell proliferation, adhesion, morphology, mobility and gene expression using real-time technologies. The results showed that fibronectin, poly-l-lysine and poly-l-ornithine improved LNCaP cells adherence and provoked cell morphology alterations, such as increase of nuclear and cellular area. These coating reagents also induced a higher expression of F-actin and reduced cell mobility. In contrast, laminin and collagen type IV did not improve adherence but promoted cell aggregation and affected cell morphology. Cells cultured in the presence of laminin displayed higher mobility than control cells. All the coating conditions significantly affected cell viability; however, they did not affect the expression of androgen receptor-regulated genes. Our comparative findings provide important insight for the selection of the ideal coating reagent and culture conditions for the cancer cell lines with respect to their effect on proliferation rate, attachment, morphology, migration, transcriptional response and cellular cytoskeleton arrangement. PMID:25375165

  11. Differential effects of tissue culture coating substrates on prostate cancer cell adherence, morphology and behavior.

    PubMed

    Liberio, Michelle S; Sadowski, Martin C; Soekmadji, Carolina; Davis, Rohan A; Nelson, Colleen C

    2014-01-01

    Weak cell-surface adhesion of cell lines to tissue culture surfaces is a common problem and presents technical limitations to the design of experiments. To overcome this problem, various surface coating protocols have been developed. However, a comparative and precise real-time measurement of their impact on cell behavior has not been conducted. The prostate cancer cell line LNCaP, derived from a patient lymph node metastasis, is a commonly used model system in prostate cancer research. However, the cells' characteristically weak attachment to the surface of tissue culture vessels and cover slips has impeded their manipulation and analysis and use in high throughput screening. To improve the adherence of LNCaP cells to the culture surface, we compared different coating reagents (poly-L-lysine, poly-L-ornithine, collagen type IV, fibronectin, and laminin) and culturing conditions and analyzed their impact on cell proliferation, adhesion, morphology, mobility and gene expression using real-time technologies. The results showed that fibronectin, poly-L-lysine and poly-L-ornithine improved LNCaP cells adherence and provoked cell morphology alterations, such as increase of nuclear and cellular area. These coating reagents also induced a higher expression of F-actin and reduced cell mobility. In contrast, laminin and collagen type IV did not improve adherence but promoted cell aggregation and affected cell morphology. Cells cultured in the presence of laminin displayed higher mobility than control cells. All the coating conditions significantly affected cell viability; however, they did not affect the expression of androgen receptor-regulated genes. Our comparative findings provide important insight for the selection of the ideal coating reagent and culture conditions for the cancer cell lines with respect to their effect on proliferation rate, attachment, morphology, migration, transcriptional response and cellular cytoskeleton arrangement.

  12. 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

  13. Bone health in patients with prostate cancer.

    PubMed

    Miñana, B; Cózar, J M; Alcaraz, A; Morote, J; Gómez-Veiga, F J; Solsona, E; Rodríguez-Antolín, A; Carballido, J

    2014-12-01

    In patients with prostate cancer, bone health is compromised by advanced age at diagnosis, androgen suppression treatments and the developmentofbone metastases. In this paper the medical literature is reviewed in order to update the state of the art on their incidence, prevention and management. A literature review about bone involvement in patients with prostate cancer in different clinical settings is performed. Decreased bone mineral density is higher in patients diagnosed of prostate cancer before starting treatment than in healthy men with the same age. During the first year of treatment, a severe loss bone density is reported due to androgen suppression therapy. From then on, loss bone density seems to slow down, persisting at long-term. It is important to know the starting point and the dynamics of loss bone in order to prevent its progression. The skeletal events have an important impact on quality of life in patients with prostate cancer. Both Denosumab and Zoledronic Acid have proven effective in reducing loss bone. The prevention and management of bone involvement in patients with prostate cancer is critical to quality of life in these patients and requires an individualized approach. Before starting a prolonged androgen deprivation, baseline risk of fracture should be evaluated in order to adopt the proper protective measures. In patients with metastases, early treatments reducing the risk of bone events should be taken into account. Copyright © 2014 AEU. Published by Elsevier Espana. All rights reserved.

  14. 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.

  15. PET/CT imaging and radioimmunotherapy of prostate cancer

    PubMed Central

    Bouchelouche, Kirsten; Tagawa, Scott T.; Goldsmith, Stanley J.; Turkbey, Baris; Capala, Jacek; Choyke, Peter

    2012-01-01

    Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an important role in the clinical management of patients with prostate cancer. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis of anatomic, functional, and molecular imaging information. Positron emission tomography (PET)/computed tomography (CT) in oncology is emerging as an important imaging tool. The most common radiotracer for PET/CT in oncology, 18F- fluorodeoxyglucose (FDG), is not very useful in prostate cancer. However, in recent years other PET tracers have improved the accuracy of PET/CT imaging of prostate cancer. Among these, choline, labelled with 18F or 11C, 11C-acetate and 18F- fluoride have demonstrated promising results, and other new radiopharmaceuticals are currently under development and evaluation in pre-clinical and clinical studies. Large prospective clinical PET/CT trials are needed to establish the role of PET/CT in prostate cancer patients. Because there are only limited available therapeutic options for advanced metastatic prostate cancer, there is an urgent need for the development of more effective treatment modalities that could improve outcome. Prostate cancer represents an attractive target for radioimmunotherapy (RIT) for several reasons, including pattern of metastatic spread (lymph nodes and bone marrow, sites with good access to circulating antibodies), and small volume disease (ideal for antigen access and antibody delivery). Furthermore, prostate cancer is also radiation sensitive. Prostate-specific membrane antigen (PSMA) is expressed by virtually all prostate cancers, and represents an attractive target for RIT. Anti PSMA RIT demonstrates antitumor activity and is well tolerated. Clinical trials are underway to further improve upon treatment efficacy and patient selection. This review focuses on the recent advances of clinical PET/CT imaging and RIT of prostate

  16. Urine biomarkers in prostate cancer.

    PubMed

    Ploussard, Guillaume; de la Taille, Alexandre

    2010-02-01

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

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

    PubMed Central

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

    2011-01-01

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

  18. Teriflunomide (leflunomide) promotes cytostatic, antioxidant, and apoptotic effects in transformed prostate epithelial cells: evidence supporting a role for teriflunomide in prostate cancer chemoprevention.

    PubMed

    Hail, Numsen; Chen, Ping; Bushman, Lane R

    2010-06-01

    Teriflunomide (TFN) is an inhibitor of de novo pyrimidine synthesis and the active metabolite of leflunomide. Leflunomide is prescribed to patients worldwide as an immunomodulatory and anti-inflammatory disease-modifying prodrug. Leflunomide inhibited the growth of human prostate cancer xenographs in mice, and leflunomide or TFN promoted cytostasis and/or apoptosis in cultured cells. These findings suggest that TFN could be useful in prostate cancer chemoprevention. We investigated the possible mechanistic aspects of this tenet by characterizing the effects of TFN using premalignant PWR-1E and malignant DU-145 human prostate epithelial cells. TFN promoted a dose- and time-dependent cytostasis or apoptosis induction in these cells. The cytostatic effects of TFN, which were reversible but not by the presence of excess uridine in the culture medium, included diminished cellular uridine levels, an inhibition in oxygen consumption, a suppression of reactive oxygen species (ROS) generation, S-phase cell cycle arrest, and a conspicuous reduction in the size and number of the nucleoli in the nuclei of these cells. Conversely, TFN's apoptogenic effects were characteristic of catastrophic mitochondrial disruption (i.e., a dissipation of mitochondrial inner transmembrane potential, enhanced ROS production, mitochondrial cytochrome c release, and cytoplasmic vacuolization) and followed by DNA fragmentation. The respiration-deficient derivatives of the DU-145 cells, which are also uridine auxotrophs, were markedly resistant to the cytostatic and apoptotic effects of TFN, implicating de novo pyrimidine synthesis and mitochondrial bioenergetics as the primary targets for TFN in the respiration competent cells. These mechanistic findings advocate a role for TFN and mitochondrial bioenergetics in prostate cancer chemoprevention.

  19. Teriflunomide (Leflunomide) Promotes Cytostatic, Antioxidant, and Apoptotic Effects in Transformed Prostate Epithelial Cells: Evidence Supporting a Role for Teriflunomide in Prostate Cancer Chemoprevention1

    PubMed Central

    Hail, Numsen; Chen, Ping; Bushman, Lane R

    2010-01-01

    Teriflunomide (TFN) is an inhibitor of de novo pyrimidine synthesis and the active metabolite of leflunomide. Leflunomide is prescribed to patients worldwide as an immunomodulatory and anti-inflammatory disease-modifying prodrug. Leflunomide inhibited the growth of human prostate cancer xenographs in mice, and leflunomide or TFN promoted cytostasis and/or apoptosis in cultured cells. These findings suggest that TFN could be useful in prostate cancer chemoprevention. We investigated the possible mechanistic aspects of this tenet by characterizing the effects of TFN using premalignant PWR-1E and malignant DU-145 human prostate epithelial cells. TFN promoted a dose- and time-dependent cytostasis or apoptosis induction in these cells. The cytostatic effects of TFN, which were reversible but not by the presence of excess uridine in the culture medium, included diminished cellular uridine levels, an inhibition in oxygen consumption, a suppression of reactive oxygen species (ROS) generation, S-phase cell cycle arrest, and a conspicuous reduction in the size and number of the nucleoli in the nuclei of these cells. Conversely, TFN's apoptogenic effects were characteristic of catastrophic mitochondrial disruption (i.e., a dissipation of mitochondrial inner transmembrane potential, enhanced ROS production, mitochondrial cytochrome c release, and cytoplasmic vacuolization) and followed by DNA fragmentation. The respiration-deficient derivatives of the DU-145 cells, which are also uridine auxotrophs, were markedly resistant to the cytostatic and apoptotic effects of TFN, implicating de novo pyrimidine synthesis and mitochondrial bioenergetics as the primary targets for TFN in the respiration competent cells. These mechanistic findings advocate a role for TFN and mitochondrial bioenergetics in prostate cancer chemoprevention. PMID:20563249

  20. Adverse Effects of Androgen Deprivation Therapy: Defining the Problem and Promoting Health Among Men with Prostate Cancer

    PubMed Central

    Saylor, Philip J.; Smith, Matthew R.

    2010-01-01

    Androgen deprivation therapy (ADT) plays a central role in the management of men with locally advanced, recurrent, and metastatic prostate cancer. Because most men diagnosed with prostate cancer will die of something other than their cancer, treatment-related adverse effects are highly relevant to their long-term health. Benefits of ADT in each clinical setting must be weighed against ADT-related adverse effects. ADT is detrimental to several metabolic end points and to bone health. ADT has been prospectively shown to cause decreased lean muscle mass, increased fat mass, weight gain, increased cholesterol and triglycerides, insulin resistance, and loss of bone mineral density. In population-based analyses it has been associated with an increased incidence of diabetes, clinical fractures, and cardiovascular disease. Data-driven recommendations for managing these adverse effects are needed. Currently the authors advocate the use of adapted practice guidelines developed to prevent diabetes, fractures, and coronary heart disease in the general population. PMID:20141678

  1. The other face of miR-17-92a cluster, exhibiting tumor suppressor effects in prostate cancer.

    PubMed

    Ottman, Richard; Levy, Jenna; Grizzle, William E; Chakrabarti, Ratna

    2016-11-08

    miR-17-92a cluster miRNAs are transcribed from a polycistronic transcription unit C13orf25 that generates six mature miRNAs, miR-17, miR-18a, miR-19a, miR-19b, miR-20a and miR-92a that are overexpressed in lung and colon cancers. Here we show that the expression of miR-17-92a miRNAs are reduced in cancerous prostate tissues compared to uninvolved areas and also in aggressive prostate cancer cells. Restoration of expression of all members of miR-17-92a cluster showed, decreased expression of cell cycle regulatory proteins cyclin D1 and SSH1; and LIMK1 and FGD4 of RhoGTPase signaling pathway. Expression of miR-17-92a miRNAs caused decreased cell proliferation, reduced activation of AKT and MAP kinases, delayed tumorigenicity and reduced tumor growth in animals. Expression of miR-17-92a miRNAs inhibited EMT via reduced cell migration and expression of mesenchymal markers while elevating expression and surface localization of the epithelial marker E-Cadherin. Expression of miR-17-92a miRNAs improved sensitivity of androgen dependent LNCaP 104-S prostate cancer cells to anti-androgen drug Casodex, AKT inhibitor MK-2206 2HCl, and docetaxel. The androgen refractory PC-3 cells also showed increased sensitivity to docetaxel, MK-2206 2HCl and Aurora kinase inhibitor VX680 upon ectopic expression of miR-17-92a cluster miRNAs. Our data demonstrate a tumor suppressor effect of miR-17-92a cluster miRNAs in prostate cancer cells and restoration of expression of these miRNAs has a therapeutic benefit for both androgen-dependent and -independent prostate cancer cells.

  2. The other face of miR-17-92a cluster, exhibiting tumor suppressor effects in prostate cancer

    PubMed Central

    Ottman, Richard; Levy, Jenna; Grizzle, William E.; Chakrabarti, Ratna

    2016-01-01

    miR-17-92a cluster miRNAs are transcribed from a polycistronic transcription unit C13orf25 that generates six mature miRNAs, miR-17, miR-18a, miR-19a, miR-19b, miR-20a and miR-92a that are overexpressed in lung and colon cancers. Here we show that the expression of miR-17-92a miRNAs are reduced in cancerous prostate tissues compared to uninvolved areas and also in aggressive prostate cancer cells. Restoration of expression of all members of miR-17-92a cluster showed, decreased expression of cell cycle regulatory proteins cyclin D1 and SSH1; and LIMK1 and FGD4 of RhoGTPase signaling pathway. Expression of miR-17-92a miRNAs caused decreased cell proliferation, reduced activation of AKT and MAP kinases, delayed tumorigenicity and reduced tumor growth in animals. Expression of miR-17-92a miRNAs inhibited EMT via reduced cell migration and expression of mesenchymal markers while elevating expression and surface localization of the epithelial marker E-Cadherin. Expression of miR-17-92a miRNAs improved sensitivity of androgen dependent LNCaP 104-S prostate cancer cells to anti-androgen drug Casodex, AKT inhibitor MK-2206 2HCl, and docetaxel. The androgen refractory PC-3 cells also showed increased sensitivity to docetaxel, MK-2206 2HCl and Aurora kinase inhibitor VX680 upon ectopic expression of miR-17-92a cluster miRNAs. Our data demonstrate a tumor suppressor effect of miR-17-92a cluster miRNAs in prostate cancer cells and restoration of expression of these miRNAs has a therapeutic benefit for both androgen-dependent and -independent prostate cancer cells. PMID:27650539

  3. The effect of dietary and exercise interventions on body weight in prostate cancer patients: a systematic review.

    PubMed

    Mohamad, Hamdan; McNeill, Geraldine; Haseen, Farhana; N'Dow, James; Craig, Leone C A; Heys, Steven D

    2015-01-01

    Prostate cancer prognosis may therefore be improved by maintaining healthy weight through diet and physical activity. This systematic review looked at the effect of diet and exercise interventions on body weight among men treated for prostate cancer. MEDLINE, EMBASE, CINAHL, and Cochrane Library databases were searched from the earliest record to August 2013. Randomized controlled trials of diet and exercise interventions in prostate cancer patients that reported body weight or body composition changes were included. A total of 20 trials were included in the review. Because of the heterogeneity of intervention components, a narrative review was conducted. Interventions were categorized as diet (n = 6), exercise (n = 8), or a combination of both diet and exercise (n = 6). The sample size ranged from 8 to 155 and the duration from 3 wk to 4 yr. Four diet interventions and 1 combined diet and exercise intervention achieved significant weight loss with mean values ranging from 0.8 kg to 6.1 kg (median 4.5 kg). Exercise alone did not lead to weight loss, though most of these trials aimed to increase fitness and quality of life rather than decrease body weight. Diet intervention, alone or in combination with exercise, can lead to weight loss in men treated for prostate cancer.

  4. Analgesic efficacy of zoledronic acid and its effect on functional status of prostate cancer patients with metastasis

    PubMed Central

    Gálvez, Rafael; Ribera, Victoria; González-Escalada, José Ramón; Souto, Alicia; Cánovas, María Luz; Castro, Andrés; Herrero, Begoña; de los Ángeles Maqueda, María; Castilforte, Matilde; Marco-Martínez, José Javier; Pérez, Concepción; Vicente-Fatela, Lorenza; MD, Consuelo Nieto; Orduña, Maria José; Padrol, Anna; Reig, Enrique; Carballido, Joaquín; Cózar, José Manuel

    2008-01-01

    Objectives A multi-centered observational study evaluated the efficacy of zoledronic acid for improving pain and mobility, and preventing skeletal-related events (SRE) (fracture, spinal compression, pain-relieving radiotherapy), in patients with prostate cancer and bone metastasis. Materials and Methods Males (n = 218) with prostate cancer and bone metastasis undergoing oncologic therapy received zoledronic acid (4 mg iv/month) for 6 months. Parameters evaluated were: 1) pain and movement after 2 consecutive doses; 2) quality of life; 3) SRE incidence and time-to-appearance. Medication tolerance and treatment satisfaction were assessed using a questionnaire. Results A total of 170 that matched all the inclusion criteria (78%) out of 218 were evaluable for efficacy. There was a measurable statistically significant reduction in pain at rest and on movement as well as an improvement in the quality of life compared with baseline. Best results were obtained with early treatment. Overall incidence of bone events was 11.2%. Of the 212 patients (97.2%) evaluable for safety, 16% suffered adverse events and 66% expressed satisfaction with the treatment Discussion Zoledronic acid is effective for reducing pain, improving mobility, and increasing the quality of life in patients with prostate cancer with bone metastasis. Its easy administration and good tolerability make zoledronic acid one of the principal therapeutic tools in the management of patients with pain associated with bone metastasis from prostate cancer. PMID:19920966

  5. Cost-effectiveness analysis of multiparametric MRI with increased active surveillance for low-risk prostate cancer in Australia.

    PubMed

    Gordon, Louisa G; James, Robbie; Tuffaha, Haitham W; Lowe, Anthony; Yaxley, John

    2017-05-01

    To evaluate the cost-effectiveness of multiparametric magnetic resonance imaging (mpMRI) to diagnose prostate cancer and direct all low-risk patients into active surveillance (AS). A Markov cohort model was developed to assess three scenarios: 1) no mpMRI and current AS; 2) mpMRI and current AS; and 3) mpMRI and increased AS. Men were tracked from diagnosis to end-of-life. Estimates to populate the model were derived from systematic reviews, meta-analyses, epidemiological publications, and national cost reports. An Australian Government perspective was used. Outcomes included healthcare costs, survival, quality-adjusted life years (QALYs), number of biopsies, and significant and insignificant cancers. Extensive sensitivity analyses were undertaken to address possible variation in the modeled inputs. Mean lifetime costs per patient were AU$23,191 for Scenario 1, AU$23,387 for Scenario 2 and AU$21,064 for Scenario 3. Corresponding QALYs were 7.81, 7.77, 7.83 for Scenarios 1, 2, and 3, respectively. At the current uptake of AS in Australia, mpMRI alone does not appear cost-effective (16.9% likelihood). However, mpMRI with AS for all men with low-risk disease is strongly cost-effective (86.9% likelihood) at a willingness-to-pay AU$50,000 per QALY gained. For the mpMRI options, for every 1000 men suspected of prostate cancer, using mpMRI would avoid 340 biopsies, detect an additional 20 significant cancers, and detect 10 fewer insignificant cancers. Diagnosis of prostate cancer through mpMRI technology would be cost-effective if it leads to increased uptake of AS for men with confirmed very-low- or low-risk prostate cancer. 2 J. MAGN. RESON. IMAGING 2017;45:1304-1315. © 2016 International Society for Magnetic Resonance in Medicine.

  6. Meharry-Johns Hopkins Center for Prostate Cancer Research

    DTIC Science & Technology

    2015-11-01

    fathers. 1. Investigate the effects of race , economic status, and psychosocial factors, on the quality of life of men diagnosed with prostate cancer. 2...examination of men with prostate cancer ("The Fathers Study"), the goals of which are (1) to investigate the effects of race , economic status, and psycho...Interviews Race | Freq. Percent ------------+----------------------------------- White | 18 75.00

  7. The association between metabolic syndrome and prostate cancer: Effect on its aggressiveness and progression.

    PubMed

    Sanchís-Bonet, A; Ortiz-Vico, F; Morales-Palacios, N; Sánchez-Chapado, M

    2015-04-01

    To evaluate the impact of metabolic syndrome and its individual components on prostate biopsy findings, the radical prostatectomy specimen and on biochemical recurrence. An observational study was conducted of 1319 men who underwent prostate biopsy between January 2007 and December 2011. The impact on the biopsy findings, the radical prostatectomy specimen and biochemical recurrence was evaluated using logistic regression and Cox regression. Of the 1319 patients, 275 (21%) had metabolic syndrome, and 517 prostate cancers were diagnosed. A greater percentage of metabolic syndrome was found among patients with prostate cancer than among patients without prostate cancer (25% vs. 18%; P=.002). Poorer results were found in the radical prostatectomy specimens (Gleason score ≥ 7, P<.001; stage ≥ T2c, P<.001; positive surgical margins, P<.001), and there was a greater percentage of biochemical recurrence in patients with metabolic syndrome than in those without metabolic syndrome (24% vs. 13%; P=.003). Metabolic syndrome behaved as an independent predictive factor of finding a Gleason score ≥ 7 for the specimen, as well as for finding a specimen stage ≥ T2c. Metabolic syndrome was also able to independently predict a greater rate of biochemical recurrence (OR: 3.6, P<.001; OR: 3.2, P=.03; HR: 1.7; respectively). Metabolic syndrome is associated with poorer findings in the radical prostatectomy specimens and is an independent prognostic factor of biochemical recurrence. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Chemopreventive effect of quercetin in MNU and testosterone induced prostate cancer of Sprague-Dawley rats.

    PubMed

    Sharmila, Govindaraj; Athirai, Thavadurainathan; Kiruthiga, Balakrishnan; Senthilkumar, Kalimuthu; Elumalai, Perumal; Arunkumar, Ramachandran; Arunakaran, Jagadeesan

    2014-01-01

    Prostate cancer becomes an ideal target for chemoprevention because of its high incidence and extended natural history. The consumption of quercetin (plant flavonoid) in diet is associated with decreased risk of disease and many cancers but then this was not elucidated in prostate malignancy. Hence, a study in which the male Sprague-Dawley rats were induced prostate cancer by hormone (testosterone) and carcinogen (MNU) and simultaneously supplemented with quercetin (200 mg/Kg body weight) thrice a week, was conducted. After the treatment period, rats were killed; ventral and dorsolateral lobes of the prostate were dissected. Histology and oxidative stress markers LPO, H2O2, and antioxidant GSH level were measured in both lobes. The lipid peroxidation, H2O2, in (MNU+T) treated rats were increased and GSH level was decreased, whereas simultaneous quercetin-treated rats reverted back to normal level in both ventral and dorsolateral regions. The different patterns of PIN were observed with associated hyperplasia and dysplasia; changes in these regions and the occurrence of this lesion were reduced in simultaneous quercetin-treated rats. The study concluded that dietary quercetin prevented MNU + T-induced prostate carcinogenesis on both ventral and dorsolateral lobes of Sprague-Dawley rats.

  9. Novel Imidazopyridine Derivatives Possess Anti-Tumor Effect on Human Castration-Resistant Prostate Cancer Cells

    PubMed Central

    Muniyan, Sakthivel; D’Cunha, Napoleon; Robinson, Tashika; Hoelting, Kyle; Dwyer, Jennifer G.; Bu, Xiu R.; Batra, Surinder K.; Lin, Ming-Fong

    2015-01-01

    Prostate cancer (PCa) is the second leading cause of cancer-related death afflicting United States males. Most treatments to-date for metastatic PCa include androgen-deprivation therapy and second-generation anti-androgens such as abiraterone acetate and enzalutamide. However, a majority of patients eventually develop resistance to these therapies and relapse into the lethal, castration-resistant form of PCa to which no adequate treatment option remains. Hence, there is an immediate need to develop effective therapeutic agents toward this patient population. Imidazopyridines have recently been shown to possess Akt kinase inhibitory activity; thus in this study, we investigated the inhibitory effect of novel imidazopyridine derivatives HIMP, M-MeI, OMP, and EtOP on different human castration-resistant PCa cells. Among these compounds, HIMP and M-MeI were found to possess selective dose- and time-dependent growth inhibition: they reduced castration-resistant PCa cell proliferation and spared benign prostate epithelial cells. Using LNCaP C-81 cells as the model system, these compounds also reduced colony formation as well as cell adhesion and migration, and M-MeI was the most potent in all studies. Further investigation revealed that while HIMP primarily inhibits PCa cell growth via suppression of PI3K/Akt signaling pathway, M-MeI can inhibit both PI3K/Akt and androgen receptor pathways and arrest cell growth in the G2 phase. Thus, our results indicate the novel compound M-MeI to be a promising candidate for castration-resistant PCa therapy, and future studies investigating the mechanism of imidazopyridine inhibition may aid to the development of effective anti-PCa agents. PMID:26121643

  10. Novel Imidazopyridine Derivatives Possess Anti-Tumor Effect on Human Castration-Resistant Prostate Cancer Cells.

    PubMed

    Ingersoll, Matthew A; Lyons, Anastesia S; Muniyan, Sakthivel; D'Cunha, Napoleon; Robinson, Tashika; Hoelting, Kyle; Dwyer, Jennifer G; Bu, Xiu R; Batra, Surinder K; Lin, Ming-Fong

    2015-01-01

    Prostate cancer (PCa) is the second leading cause of cancer-related death afflicting United States males. Most treatments to-date for metastatic PCa include androgen-deprivation therapy and second-generation anti-androgens such as abiraterone acetate and enzalutamide. However, a majority of patients eventually develop resistance to these therapies and relapse into the lethal, castration-resistant form of PCa to which no adequate treatment option remains. Hence, there is an immediate need to develop effective therapeutic agents toward this patient population. Imidazopyridines have recently been shown to possess Akt kinase inhibitory activity; thus in this study, we investigated the inhibitory effect of novel imidazopyridine derivatives HIMP, M-MeI, OMP, and EtOP on different human castration-resistant PCa cells. Among these compounds, HIMP and M-MeI were found to possess selective dose- and time-dependent growth inhibition: they reduced castration-resistant PCa cell proliferation and spared benign prostate epithelial cells. Using LNCaP C-81 cells as the model system, these compounds also reduced colony formation as well as cell adhesion and migration, and M-MeI was the most potent in all studies. Further investigation revealed that while HIMP primarily inhibits PCa cell growth via suppression of PI3K/Akt signaling pathway, M-MeI can inhibit both PI3K/Akt and androgen receptor pathways and arrest cell growth in the G2 phase. Thus, our results indicate the novel compound M-MeI to be a promising candidate for castration-resistant PCa therapy, and future studies investigating the mechanism of imidazopyridine inhibition may aid to the development of effective anti-PCa agents.

  11. Reconstructing the Prostate Cancer Transcriptional Regulatory Network

    DTIC Science & Technology

    2010-07-01

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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. Image-guided conformation arc therapy for prostate cancer: Early side effects

    SciTech Connect

    Soete, Guy . E-mail: guy.soete@az.vub.ac.be; Verellen, Dirk; Michielsen, Dirk; Rappe, Bernard; Keuppen, Frans; Storme, Guy

    2006-11-15

    Purpose: To evaluate early side effects in prostate cancer patients treated with image-guided conformation arc therapy (IGCAT) using a minimultileaf collimator and daily X-ray-assisted patient positioning. Methods and Materials: Between May 2000 and November 2004, 238 cT1-T3N0M0 tumors were treated with doses of 70 or 78 Gy. Seventy patients also received neoadjuvant or concurrent hormonal treatment. Median follow-up is 18 months (range, 4-55 months). Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer toxicity scoring system was used to evaluate early side effects. Results: Grade 1, 2, and >2 acute side effects occurred in 19, 6, and 0% (gastrointestinal) and 37, 16, and 0% (genitourinary) of the patients. No relation between radiation dose and early side effects was observed. Conclusion: Patients treated with image-guided conformation arc therapy experience a low rate of Grade 2 (i.e., requiring medication) early side effects. The definitive evaluation of late side effects and biochemical control requires further follow-up.

  17. Effects of Hedera helix L. extracts on rat prostate cancer cell proliferation and motility

    PubMed Central

    Gumushan-Aktas, Hatice; Altun, Seyhan

    2016-01-01

    Hedera helix L., a member of Araliaceae family, has antiproliferative, cytotoxic, antimicrobial, antifungal, antiprotozoal and anti-inflammatory effects, and is used in cosmetics. The aim of the present study was to investigate the effect of treatment with extracts of leaves and unripened fruits of H. helix on rat prostate cancer cell lines with markedly different metastatic potentials: Mat-LyLu cells (strongly metastatic) and AT-2 cells (weakly metastatic). The effects of the extracts on cell kinetics and migration were determined. Tetrodotoxin was used to block the voltage-gated sodium channels (VGSCs) associated specifically with Mat-LyLu cells. Cell proliferation was detected spectrophotometrically using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. The mitotic index was determined using the Feulgen staining method. Lateral motility was quantified by wound-healing assays. The results of the present study demonstrated that cell kinetics (proliferation and mitotic activity) and motility were inhibited by ethanolic leaf extract of H. helix. The ethanolic extract of H. helix fruit suppressed Mat-LyLu cell migration, with no effect on proliferation. The opposite effects were observed in AT-2 cells; migration was not affected but proliferation was inhibited. In conclusion, the ethanolic fruit extract of H. helix may inhibit the cell migration of Mat-LyLu cells by blocking VGSCs. However, the effect of ethanolic leaf extract of H. helix treatment on the lateral motility of the cancer cells is unclear. PMID:27698887

  18. 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.

  19. The use of dietary supplements to alleviate androgen deprivation therapy side effects during prostate cancer treatment.

    PubMed

    Dueregger, Andrea; Heidegger, Isabel; Ofer, Philipp; Perktold, Bernhard; Ramoner, Reinhold; Klocker, Helmut; Eder, Iris E

    2014-10-21

    Prostate cancer (PCa), the most commonly diagnosed cancer and second leading cause of male cancer death in Western societies, is typically androgen-dependent, a characteristic that underlies the rationale of androgen deprivation therapy (ADT). Approximately 90% of patients initially respond to ADT strategies, however many experience side effects including hot flashes, cardiotoxicity, metabolic and musculoskeletal alterations. This review summarizes pre-clinical and clinical studies investigating the ability of dietary supplements to alleviate adverse effects arising from ADT. In particular, we focus on herbal compounds, phytoestrogens, selenium (Se), fatty acids (FA), calcium, and Vitamins D and E. Indeed, there is some evidence that calcium and Vitamin D can prevent the development of osteoporosis during ADT. On the other hand, caution should be taken with the antioxidants Se and Vitamin E until the basis underlying their respective association with type 2 diabetes mellitus and PCa tumor development has been clarified. However, many other promising supplements have not yet been subjected large-scale clinical trials making it difficult to assess their efficacy. Given the demographic trend of increased PCa diagnoses and dependence on ADT as a major therapeutic strategy, further studies are required to objectively evaluate these supplements as adjuvant for PCa patients receiving ADT.

  20. The Use of Dietary Supplements to Alleviate Androgen Deprivation Therapy Side Effects during Prostate Cancer Treatment

    PubMed Central

    Dueregger, Andrea; Heidegger, Isabel; Ofer, Philipp; Perktold, Bernhard; Ramoner, Reinhold; Klocker, Helmut; Eder, Iris E.

    2014-01-01

    Prostate cancer (PCa), the most commonly diagnosed cancer and second leading cause of male cancer death in Western societies, is typically androgen-dependent, a characteristic that underlies the rationale of androgen deprivation therapy (ADT). Approximately 90% of patients initially respond to ADT strategies, however many experience side effects including hot flashes, cardiotoxicity, metabolic and musculoskeletal alterations. This review summarizes pre-clinical and clinical studies investigating the ability of dietary supplements to alleviate adverse effects arising from ADT. In particular, we focus on herbal compounds, phytoestrogens, selenium (Se), fatty acids (FA), calcium, and Vitamins D and E. Indeed, there is some evidence that calcium and Vitamin D can prevent the development of osteoporosis during ADT. On the other hand, caution should be taken with the antioxidants Se and Vitamin E until the basis underlying their respective association with type 2 diabetes mellitus and PCa tumor development has been clarified. However, many other promising supplements have not yet been subjected large-scale clinical trials making it difficult to assess their efficacy. Given the demographic trend of increased PCa diagnoses and dependence on ADT as a major therapeutic strategy, further studies are required to objectively evaluate these supplements as adjuvant for PCa patients receiving ADT. PMID:25338271

  1. The effects of multidisciplinary rehabilitation: RePCa—a randomised study among primary prostate cancer patients

    PubMed Central

    Dieperink, K B; Johansen, C; Hansen, S; Wagner, L; Andersen, K K; Minet, L R; Hansen, O

    2013-01-01

    Background: The objective of this study is the effectiveness of multidisciplinary rehabilitation on treatment-related adverse effects after completed radiotherapy in patients with prostate cancer (PCa). Methods: In a single-centre oncology unit in Odense, Denmark, 161 PCa patients treated with radiotherapy and androgen deprivation therapy were randomly assigned to either a programme of two nursing counselling sessions and two instructive sessions with a physical therapist (n=79) or to usual care (n=82). Primary outcome was Expanded Prostate Cancer Index Composite (EPIC-26) urinary irritative sum-score. Before radiotherapy, pre-intervention 4 weeks after radiotherapy, and after a 20-week intervention, measurements included self-reported disease-specific quality of life (QoL; EPIC-26, including urinary, bowel, sexual, and hormonal symptoms), general QoL (Short-form-12, SF-12), pelvic floor muscle strength (Modified Oxford Scale), and pelvic floor electromyography. Intension-to-treat analyses were made with adjusted linear regression. Results: The intervention improved, as compared with controls, urinary irritative sum-score 5.8 point (Cohen's d=0.40; P=0.011), urinary sum-score (d=0.34; P=0.023), hormonal sum-score (d=0.19; P=0.018), and the SF-12 Physical Component Summary, d=0.35; P=0.002. Patients with more severe impairment gained most. Pelvic floor muscle strength measured by electromyography declined in both groups, P=0.0001. Conclusion: Multidisciplinary rehabilitation in irradiated PCa patients improved urinary and hormonal symptoms, and SF-12 physical QoL. PMID:24169342

  2. 5-Aminoimidazole-4-Carboxamide Riboside Enhances Effect of Ionizing Radiation in PC3 Prostate Cancer Cells

    SciTech Connect

    Isebaert, Sofie F.; Swinnen, Johannes V.; McBride, William H.; Begg, Adrian C.; Haustermans, Karin M.

    2011-12-01

    Purpose: The nucleoside 5-aminoimidazole-4-carboxamide riboside (AICAR) is a low-energy mimetic and adenosine monophosphate (AMP)-activated protein kinase (AMPK) agonist that can affect the phenotype of malignant cells by diminishing their anabolism. It does this by being converted to 5-aminoimidazole-4-carboxamide ribotide (ZMP), an AMP analog. We combined this promising antineoplastic agent with ionizing radiation in an attempt to increase its efficacy. Methods and Materials: The effect of AICAR on cell proliferation, cell viability, apoptosis, reactive oxygen species production, radiosensitivity, and AMPK activation was determined in the human prostate cancer cell line PC3. To elucidate the radiosensitizing mechanism, clonogenic survival assays in the presence of a drug agonist or antagonist or with small interfering RNA targeting AMPK were done, as well as measurements of ZMP production and double strand break repair. Moreover, immunoblot analysis of the radiation response signaling pathways after AICAR treatment was performed. Results: The incubation of human PC3 prostate cancer cells with AICAR-activated AMPK inhibited cell proliferation, decreased viability, increased apoptosis, and generated reactive oxygen species in a dose- and time-dependent manner. None of these endpoints gave more than additive effects when radiation was added. Radiosensitization was observed but only after 72 hours of treatment with 250 {mu}M AICAR, suggesting that it was independent of AMPK activation. This finding was confirmed by small interfering RNA knockdown of AMPK. The mechanism of radiosensitization was associated with imbalanced deoxynucleotide pools owing to ZMP accumulation after AICAR administration that interfered with DNA repair. Conclusions: Our findings on the favorable interaction between low doses of AICAR and ionizing radiation in PC3 cells could open new perspectives for the clinical use of this or similar compounds. However, additional research is still required

  3. Natural history of prostate cancer.

    PubMed

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

    2014-06-01

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

  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. High biologically effective dose radiation therapy using brachytherapy in combination with external beam radiotherapy for high-risk prostate cancer

    PubMed Central

    Wada, Akinori; Kohno, Naoaki

    2017-01-01

    Purpose To evaluate the outcomes of high-risk prostate cancer patients treated with biologically effective dose (BED) ≥ 220 Gy of high-dose radiotherapy, using low-dose-rate (LDR) brachytherapy in combination with external beam radiotherapy (EBRT) and short-term androgen deprivation therapy (ADT). Material and methods From 2005 to 2013, a total of 143 patients with high-risk prostate cancer were treated by radiotherapy of BED ≥ 220 Gy with a combination of LDR brachytherapy, EBRT, and androgen deprivation therapy (ADT). The high-risk patients in the present study included both high-risk and very high-risk prostate cancer. The number of high-risk features were: 60 patients with 1 high-risk factor (42%), 61 patients with 2 high-risk factors (43%), and 22 patients with 3 high-risk factors (15%) including five N1 disease. External beam radiotherapy fields included prostate and seminal vesicles only or whole pelvis depending on the extension of the disease. Biochemical failure was defined by the Phoenix definition. Results Six patients developed biochemical failure, thus providing a 5-year actual biochemical failure-free survival (BFFS) rate of 95.2%. Biochemical failure was observed exclusively in cases with distant metastasis in the present study. All six patients with biochemical relapse had clinical failure due to bone metastasis, thus yielding a 5-year freedom from clinical failure (FFCF) rate of 93.0%. None of the cases with N1 disease experienced biochemical failure. We observed four deaths, including one death from prostate cancer, therefore yielding a cause-specific survival (CSS) rate of 97.2%, and an overall survival (OS) rate of 95.5%. Conclusions High-dose (BED ≥ 220 Gy) radiotherapy by LDR in combination with EBRT has shown an excellent outcome on BFFS in high-risk and very high-risk cancer, although causal relationship between BED and BFFS remain to be explained further. PMID:28344597

  6. Effects of a Fluorescent Myosin Light Chain Phosphatase Inhibitor on Prostate Cancer Cells

    PubMed Central

    Grindrod, Scott; Suy, Simeng; Fallen, Shannon; Eto, Masumi; Toretsky, Jeffrey; Brown, Milton L.

    2011-01-01

    Myosin light chain phosphatase (MLCP) is an enzyme important to regulation of cell cycle and motility that is shown to be upregulated in aggressive prostate cancer cells and tissue. We developed a fluorescent small molecule inhibitor of MLCP using structure based design in recombinant protein phosphatase 1C. Several best fit compounds were synthesized and evaluated by their inhibition of MLCP/32P-MLC dephosphorylation, which resulted in the identification of novel MLCP inhibitors. Androgen dependent (AD) and castration resistant prostate cancer cell (CRPC) lines were treated with the lead inhibitor resulting in decreased growth rate, reduced DNA synthesis, and G2/M cell cycle arrest. Moreover, CRPC cell lines showed an increased sensitivity to drug treatment having GI50 values four times lower than the AD prostate cancer cell line. This was reinforced by reduced BrdU DNA incorporation into CRPC cells compared to AD cells. β-actin disruption was also seen at much lower drug concentrations in CR cells which caused a dose dependent reduction in cellular chemotaxis of PC-3 cells. Since there are currently few clinical therapeutics targeting CR prostate cancer, MLCP represents a new target for preclinical and clinical development of new potential therapeutics which inhibit this disease phenotype. PMID:22655237

  7. Prostate Cancer Detection Using Composite Impedance Metric.

    PubMed

    Khan, Shadab; Mahara, Aditya; Hyams, Elias S; Schned, Alan R; Halter, Ryan J

    2016-12-01

    Prostate cancer (PCa) recurrences are often predicted by assessing the status of surgical margins (SM)- positive surgical margins (PSM) increase the chances of biochemical recurrence by 2-4 times which may lead to PCa recurrence. To this end, an electrical impedance acquisition system with a microendoscopic probe was employed in an ex-vivo study of human prostates. This system measures the tissue bioimpedance over a range of frequencies (1 kHz to 1MHz), and computes a number of Composite Impedance Metrics (CIM). A classifier trained using CIM data can be used to classify tissue as benign or cancerous. The system was used to collect the impedance spectra from 14 excised prostates, which were obtained from men undergoing radical prostatectomy, for a total of 23 cancerous and 53 benign measurements. The data revealed statistically significant (p < 0.05) differences in the impedance properties of the benign and tumorous tissues, and among the measurements taken on the apical, base, and lateral surface of the prostate. Further, in the leave-one-patient-out cross validation, a maximum predictive accuracy of 90.79% was achieved by combining high frequency CIM phase data to train a support vector machine classifier with a radial basis function kernel. The observations are consistent with the physiology and morphology of benign and malignant prostate tissue. CIMs were found to be an effective tool in distinguishing benign from cancerous tissues.

  8. The effects of androgen deprivation therapy on cardiac function and heart failure: implications for management of prostate cancer.

    PubMed

    Edelman, Scott; Butler, Javed; Hershatter, Bruce W; Khan, Mohammad K

    2014-12-01

    Conflicting clinical evidence regarding the possible association between androgen deprivation therapy (ADT) with heart failure in men with prostate cancer is reviewed, including 2 population-based registries showing such an association, and 1 showing no association. Studies of the effects of androgens on cardiomyocyte contractility at the molecular level, the effects of testosterone on the cardiovascular system, particularly cardiac function, and the beneficial effects of testosterone therapy for patients with heart failure might help illuminate this controversy. Future studies are needed to evaluate the effect of ADT on end points of heart failure. The authors weigh the possible adverse effects of ADT on cardiac function and heart failure against its known benefits to cancer outcomes, defined according to published, randomized trials, in a discussion of the implications of the preclinical and clinical literature on the management of prostate cancer in men at risk for heart failure. In the absence of conclusive evidence that ADT causes heart failure, the authors discuss clinical situations in which ADT may be delayed, given on a short-term or intermittent basis, or withheld from treatment with the goal of reducing the risks of heart failure without compromising prostate cancer outcomes.

  9. The antiproliferative effects of biologically active isomers of conjugated linoleic acid on human colorectal and prostatic cancer cells.

    PubMed

    Palombo, John D; Ganguly, Aniruddha; Bistrian, Bruce R; Menard, Michael P

    2002-03-28

    The antiproliferative effects of two commercial preparations of conjugated linoleic acid (CLA) and their constituent isomers, cis-9, trans-11 (c9,t11)-CLA, c9,c11-CLA, and t10,c12-CLA, were determined in vitro using human colorectal (HT-29, MIP-101) and prostate (PC-3) carcinoma cells adapted to serum-free medium. The antiproliferative effects of the preparations were dependent upon the type and concentration of CLA isomer present. The t10,c12-CLA isomer exhibited the greatest potency against colorectal cancer proliferation, and the c9,t11 and t10,c12 isomers were moderately effective against prostate cancer. The t10,c12 isomer induced caspase-dependent apoptosis in MIP-101 and PC-3 cells. The results are the first to demonstrate that physiologic levels of two CLA preparations, their constituent isomers, and the c9,t11-CLA elongation product, c11,t13-conjugated eicosadienoic acid, induce dose-dependent inhibitory effects on cancer proliferation in vitro. Novel CLA preparations may prove effective as chemopreventive supplements for individuals at risk of or diagnosed with colorectal or prostate cancer.

  10. Screening for prostate cancer: the current evidence and guidelines controversy.

    PubMed

    Gomella, Leonard G; Liu, Xiaolong S; Trabulsi, Edouard J; Kelly, Wm Kevin; Myers, Ronald; Showalter, Timothy; Dicker, Adam; Wender, Richard

    2011-10-01

    Prostate cancer presents a global public health dilemma. While screening with prostate specific antigen (PSA) has led to more men diagnosed with prostate cancer than in previous years, the potential for negative effects from over-diagnosis and treatment cannot be ignored. We reviewed Medline for recent articles that discuss clinical trials, evidence based recommendations and guidelines from major medical organizations in the United States and worldwide concerning prostate cancer screening. Results from the European Randomized Screening for Prostate Cancer (ERSPC), the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, and Göteborg Swedish trials regarding prostate screening are controversial with the ERSPC and Göteborg showing a reduction in prostate cancer mortality and the PLCO trial showing no benefit. Recommendations from the American Urological Association (AUA), Japanese Urological Association (JUA), and National Comprehensive Cancer Network (NCCN) have recommended that all men obtain a baseline PSA beginning at age 40. The American Cancer Society (ACS) stratifies screening recommendations based on age and risk, but states that screening should take place only after an informed discussion between provider and patient. The United States Preventative Health Service Task Force (USPSTF) states that evidence is insufficient to assess the risks and benefits of prostate cancer screening in men younger than 75 years. Other major international health organizations offer a similar reserved approach or recommend against screening for prostate cancer. Most groups indicate that screening to determine who should undergo prostate biopsy typically includes both a serum PSA and digital rectal examination, with the latest ACS publications noting that the rectal exam is optional. A common theme from all groups is that an informed discussion with the patients is strongly recommended and that screening does increase the number of men diagnosed with non

  11. National Cancer Institute Prostate Cancer Genetics Workshop.

    PubMed

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

    2011-05-15

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

  12. Motexafin lutetium-photodynamic therapy of prostate cancer: Short and long term effects on PSA

    PubMed Central

    Patel, Hiral; Mick, Rosemarie; Finlay, Jarod; Zhu, Timothy C.; Rickter, Elizabeth; Cengel, Keith A.; Malkowicz, S. Bruce; Hahn, Stephen M.; Busch, Theresa M.

    2009-01-01

    Purpose: The time course of serum PSA response to photodynamic therapy (PDT) of prostate cancer was measured. Experimental Design: Seventeen patients were treated in a Phase I trial of motexafin lutetium-PDT. PDT dose was calculated in each patient as the product of the ex vivo-measured pre-PDT photosensitizer level and the in situ-measured light dose. Serum PSA level was measured within two months prior to PDT (baseline), and at day 1; weeks 1-3; months 1, 2 and 3; months 4-6 and months 7-11 after PDT. Results: At 24h after PDT, serum PSA increased by 98±36% (mean ± SE) relative to baseline levels (p=0.007). When patients were dichotomized based on median PDT dose, those who received high PDT dose demonstrated a 119±52% increase in PSA compared to a 54±27% increase in patients treated at low PDT dose. Patients treated with high vs. low PDT dose demonstrated a median biochemical delay of 82 vs. 43 days (p=0.024), with biochemical delay defined as the length of time between PDT and a nonreversible increase in PSA to a value ≥baseline. Conclusions: Results show PDT to induce large, transient increases in serum PSA levels. Patients who experienced high PDT dose demonstrated greater short-term increase in PSA and a significantly more durable PSA response (biochemical delay). These data strongly promote the need for individualized delivery of PDT dose and assessment of treatment effect in PDT of prostate cancer. Information gained from such patient-specific measurements could facilitate the introduction of multiple PDT sessions in patients who would benefit. PMID:18676760

  13. Lithium chloride has a biphasic effect on prostate cancer stem cells and a proportional effect on midkine levels

    PubMed Central

    Erguven, Mine; Oktem, Gulperi; Kara, Ali Nail; Bilir, Ayhan

    2016-01-01

    Prostate cancer (PCa) is the second most frequent type of cancer in men worldwide and the levels of differentiation growth factor midkine (MK) are increased in PCa. Cancer and/or the treatment process itself may lead to psychiatric disorders. Lithium chloride (LiCl) has anti-manic properties and has been used in cancer therapy; however, it has a queried safety profile. In addition, cancer stem cells are responsible for the heterogeneous phenotype of tumor cells; they are involved in progression, metastasis, recurrence and therapy resistance in various cancer types. The aims of the present study were to investigate the effect of different concentrations of LiCl on PCa stem cells (whether a shift from tumorigenic to non-tumorigenic cells occurs) and to determine if these results can be explained through changes in MK levels. Monolayer and spheroid cultures of human prostate stem cells and non-stem cells were incubated with low (1, 10 µM) and high (100, 500 µM) concentrations of LiCl for 72 h. Cell proliferation, apoptotic indices, MK levels and ultrastructure were evaluated. Cells stimulated with low concentrations showed high proliferation, low apoptotic indices, high MK levels and more healthy ultrastructure. Opposite results were obtained at high concentrations. Furthermore, stem cells were more sensitive to stimulation and more resistant to inhibition than non-stem cells. LiCl exhibited concentration-dependent effects on stem cell and non-stem cell groups. MK levels were not involved in the biphasic effect of LiCl; however, they were proportionally affected. To the best of our knowledge, the present study was the first to show the effect of LiCl on PCa stem cells through MK. PMID:27703531

  14. Micellar Drug Delivery and Proteomics Analysis for Effective Treatment of Resistant Prostate Cancer

    DTIC Science & Technology

    2015-12-01

    conjugated micelles carrying CBDIV17 in an ectopic athymic mouse model of prostate cancer. MATERIALS AND METHODS Materials 2, 2-Bis(hydroxymethyl... Materials and Methods Materials PTX and CYA were purchased from LC Labs (Woburn, MA). SYBR Green real-time PCR master mix and reverse transcription...Contributed reagents/ materials /analysis tools: RIM. Wrote the paper: SS DC SWB RIM. References 1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, et al. (2009) Cancer

  15. Late radiation effects to the rectum and anus after treatment for prostate cancer; validity of the LENT/SOMA score.

    PubMed

    Lund, Jo-Å; Kaasa, Stein; Wibe, Arne; Widmark, Anders; Fransson, Per

    2013-05-01

    The Late Effects Normal Tissue/Subjective Objective Management Analytic (LENT/SOMA) system for grading of side effects after radiotherapy was proposed several years ago. Only a few studies have previously been performed on the validity of the LENT/SOMA. The aim of the present study was to validate the LENT/SOMA scoring system for recto-anal side effects after treatment for prostate cancer in a randomized trial. A total of 875 patients with locally advanced prostate cancer were randomized to either hormonal treatment alone or hormonal treatment plus radiotherapy in the Scandinavian Prostate Cancer Group 7 (SPCG-7) study. At least three years after treatment was started, the 178 patients that were randomized at St. Olavs Hospital were approached. One hundred and three patients of these accepted inclusion. The side effects according to LENT/SOMA were graded by oncologist and nurse. In addition, side effects were graded according to the European Organisation for Research and Treatment of Cancer and the Radiation Therapy Oncology Group (EORTC/RTOG) toxicity scale and patient-reported health-related quality of life (HRQOL) questionnaires. Content/face validity, sensitivity and inter-rater reliability of the LENT/SOMA tables for rectum were analyzed. Content/face analysis of LENT/SOMA revealed serious problems. Significant correlations (Spearman's rho > 0.4) were found between three of 15 LENT/SOMA items and similar HRQOL items. LENT/SOMA score made it possible to detect significant differences between the two groups of patients (p < 0.001), EORTC/RTOG toxicity score did not (p = 0.138). Inter-rater reliability was acceptable. LENT/SOMA scoring system for recto-anal side effects after radiotherapy for prostate cancer displays serious difficulties in the present study. Replacement of LENT/SOMA tables for rectum by a combination of patient-reported HRQOL questionnaires, clinical examination and objective physiological measurements might be called for.

  16. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial.

    PubMed

    Buys, Saundra S; Partridge, Edward; Black, Amanda; Johnson, Christine C; Lamerato, Lois; Isaacs, Claudine; Reding, Douglas J; Greenlee, Robert T; Yokochi, Lance A; Kessel, Bruce; Crawford, E David; Church, Timothy R; Andriole, Gerald L; Weissfeld, Joel L; Fouad, Mona N; Chia, David; O'Brien, Barbara; Ragard, Lawrence R; Clapp, Jonathan D; Rathmell, Joshua M; Riley, Thomas L; Hartge, Patricia; Pinsky, Paul F; Zhu, Claire S; Izmirlian, Grant; Kramer, Barnett S; Miller, Anthony B; Xu, Jian-Lun; Prorok, Philip C; Gohagan, John K; Berg, Christine D

    2011-06-08

    Screening for ovarian cancer with cancer antigen 125 (CA-125) and transvaginal ultrasound has an unknown effect on mortality. To evaluate the effect of screening for ovarian cancer on mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Randomized controlled trial of 78,216 women aged 55 to 74 years assigned to undergo either annual screening (n = 39,105) or usual care (n = 39,111) at 10 screening centers across the United States between November 1993 and July 2001. Intervention The intervention group was offered annual screening with CA-125 for 6 years and transvaginal ultrasound for 4 years. Participants and their health care practitioners received the screening test results and managed evaluation of abnormal results. The usual care group was not offered annual screening with CA-125 for 6 years or transvaginal ultrasound but received their usual medical care. Participants were followed up for a maximum of 13 years (median [range], 12.4 years [10.9-13.0 years]) for cancer diagnoses and death until February 28, 2010. Mortality from ovarian cancer, including primary peritoneal and fallopian tube cancers. Secondary outcomes included ovarian cancer incidence and complications associated with screening examinations and diagnostic procedures. Ovarian cancer was diagnosed in 212 women (5.7 per 10,000 person-years) in the intervention group and 176 (4.7 per 10,000 person-years) in the usual care group (rate ratio [RR], 1.21; 95% confidence interval [CI], 0.99-1.48). There were 118 deaths caused by ovarian cancer (3.1 per 10,000 person-years) in the intervention group and 100 deaths (2.6 per 10,000 person-years) in the usual care group (mortality RR, 1.18; 95% CI, 0.82-1.71). Of 3285 women with false-positive results, 1080 underwent surgical follow-up; of whom, 163 women experienced at least 1 serious complication (15%). There were 2924 deaths due to other causes (excluding ovarian, colorectal, and lung cancer) (76.6 per 10,000 person

  17. Prostate Cancer Prevention Through Induction of Phase 2 Enzymes

    DTIC Science & Technology

    2001-04-01

    enzymes. During our Phase I Award, we identified sulforaphane as the most potent inducer of carcinogen defenses in the prostate cell. We have...characterized global effects of sulforaphane in prostate cancer cell lines using cDNA microarray technology that allows large-scale determination of changes...of sulforaphane ) and decreased risk of prostate cancer. These findings argue strongly for a preventive intervention trial involving supplementation

  18. The Prostate Cancer Biorepository Network (PCBN)

    DTIC Science & Technology

    2016-10-01

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

  19. Complementary and alternative therapies for advanced prostate cancer.

    PubMed

    Smith, M R

    2001-06-01

    This article reviews complementary and alternative therapies for advanced prostate cancer. This is not a comprehensive survey of nontraditional therapies for prostate cancer. Rather, this review focuses on alternative and complementary therapies with published studies to evaluate efficacy and safety. Three areas are addressed: alternative forms of hormonal therapy, management of side effects of hormonal therapy, and management of skeletal complications.

  20. Utilizing a Narrative Approach to Increasing Intimacy after Prostate Cancer

    ERIC Educational Resources Information Center

    McCoy, Megan; Stinson, Morgan A.; Bermudez, J. Maria; Gladney, Leslie A.

    2013-01-01

    Attitudes about sexual intimacy are an important aspect of relationship satisfaction, especially for couples dealing with prostate cancer. Prostate cancer can have profound effects on men and their partners, and more research is needed to better understand potential sexual barriers for these couples. Five major themes identified in the literature…

  1. Utilizing a Narrative Approach to Increasing Intimacy after Prostate Cancer

    ERIC Educational Resources Information Center

    McCoy, Megan; Stinson, Morgan A.; Bermudez, J. Maria; Gladney, Leslie A.

    2013-01-01

    Attitudes about sexual intimacy are an important aspect of relationship satisfaction, especially for couples dealing with prostate cancer. Prostate cancer can have profound effects on men and their partners, and more research is needed to better understand potential sexual barriers for these couples. Five major themes identified in the literature…

  2. Prostate Cancer Research Training in Health Disparities for Minority Undergraduates

    DTIC Science & Technology

    2014-04-01

    Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite...and they also received expert presentations from external prostate cancer researchers from Howard University, Washington DC and Atlanta GA... Okoro ). Project 2: (Ashmit Mittal): Effects of Pim1 Inhibitor on Prostate Cancer Tumorigenesis. (Mentors: Dr. Abdulkadir, Irina Doubinskaia

  3. 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

  4. Effectiveness of community-based football compared to usual care in men with prostate cancer: Protocol for a randomised, controlled, parallel group, multicenter superiority trial (The FC Prostate Community Trial).

    PubMed

    Bjerre, Eik; Bruun, Ditte Marie; Tolver, Anders; Brasso, Klaus; Krustrup, Peter; Johansen, Christoffer; Christensen, Robin; Rørth, Mikael; Midtgaard, Julie

    2016-10-03

    Prostate cancer is the most common non-cutaneous malignancy in men. Today most patients may expect to live years following the diagnosis and may thus experience significant morbidity due to disease progression and treatment toxicity. In order to address some of these problems exercise has been suggested and previously studies have shown improvements of disease specific quality of life and a reduction in treatment-related toxicity. Cohort studies with long term follow up have suggested that physical activity is associated with improved survival in prostate cancer patients. Previously one randomised controlled trial has examined the efficacy of football in prostate cancer patients undergoing androgen deprivation therapy to usual care and reported positive effects on lean body mass and bone markers. Against this background, we wish to examine the effectiveness of community-based football for men diagnosed with prostate cancer. Using a randomised controlled parallel group, multicenter, superiority trial design, two hundred prostate cancer patients will be recruited and randomised (1:1) to either community-based football one hour twice weekly or to a control group. The intervention period will be six months. The primary outcome is quality of life assessed after 12 weeks based on the change from baseline in the Functional Assessment of Cancer Therapy-Prostate questionnaire. Secondary outcomes are change from baseline to six months in quality of life, lean body mass, fat mass, whole body and regional bone markers, as well as physical activity and functional capacity at 12 weeks and six months. Safety outcome variables will be falls resulting in seeking medical assessment and fractures during the six-month period. Football is viewed as a case for non-professional, supervised community-based team sport for promoting long-term physical activity in men diagnosed with prostate cancer. This randomised trial will provide data on effectiveness and safety for men with prostate

  5. Prostate Cancer Research Training Program

    DTIC Science & Technology

    2014-05-01

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

  6. 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

  7. Complementary medicine down-regulates side-effects of hormone therapy in prostate cancer patients.

    PubMed

    Beuth, Josef; Van Leendert, Rudolf; Pempelfort, Kirsten; Schneider, Berthold; Grund, Christina; Engelmann, Udo

    2014-01-01

    The present clinical investigation was performed to evaluate the benefits of complementary medicine in prostate cancer patients undergoing hormone therapy (HT). Patients (N=93) were treated according to international guidelines. All patients suffered from side-effects induced by the HT. To reduce the side-effects, the patients were complementarily treated with a combination of sodium selenite, proteolytic plant enzymes and Lens culinaris (Lc) lectin. On case report formulas (CRFs), self assessment of defined side-effects of HT (arthralgia, mucosal dryness, bone pain and hot flushes) were documented before (T-0) and on days 25 (T-1) and 50 (T-2) after complementary treatment. Validation was carried-out by scoring from 1 (no side-effects/optimal tolerability) to 6 (extreme side-effects/extremely bad tolerability), however, only patients suffering from severe side-effects (symptom scores >3) were enrolled in this investigation. The severity of side-effects of HT was reduced by complementary treatment with sodium selenite, proteolytic plant enzymes and Lc-lectin. The mean scores of side-effects declined for arthralgia from 4.72 (T-0) to 3.66 (T-1) to 2.76 (T-2), for mucosal dryness from 4.45 (T-0) to 3.65 (T-1) to 2.90 (T-2), for bone pain from 4.74 (T-0) to 3.44 (T-1) to 2.82 (T-2), for hot flushes from 4.97 (T-0) to 3.70 (T-1) to 3.15 (T-2). The reduced severity of the side-effects was statistically significant (p<0.001) for T-1 and T-2, compared to T-0. This investigation demonstrates benefits of indication-based complementary treatment with the combination of sodium selenite, proteolytic plant enzymes and Lc-lectin in prostate cancer patients, e.g. reduction of side-effects of HT. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  8. Functional role and tobacco smoking effects on methylation of CYP1A1 gene in prostate cancer

    PubMed Central

    Kato, Taku; Hashimoto, Yutaka; Yamamura, Soichiro; Fukuhara, Shinichiro; Wong, Darryn K.; Shiina, Marisa; Imai-Sumida, Mitsuho; Majid, Shahana; Saini, Sharanjot; Shiina, Hiroaki; Nakajima, Koichi; Deng, Guoren; Dahiya, Rajvir; Tanaka, Yuichiro

    2016-01-01

    Cytochrome P450 (CYP) 1A1 is a phase I enzyme that can activate various compounds into reactive forms and thus, may contribute to carcinogenesis. In this study, we investigated the expression, methylation status, and functional role of CYP1A1 on prostate cancer cells. Increased expression of CYP1A1 was observed in all cancer lines (PC-3, LNCaP, and DU145) compared to BPH-1 (P < 0.05); and was enhanced further by 5-aza-2′-deoxycytidine treatment (P < 0.01). Methylation-specific PCR (MSP) and sequencing of bisulfite-modified DNA of the xenobiotic response element (XRE) enhancer site XRE-1383 indicated promoter methylation as a regulator of CYP1A1 expression. In tissue, microarrays showed higher immunostaining of CYP1A1 in prostate cancer than normal and benign prostatic hyperplasia (BPH; P < 0.001), and methylation analyses in clinical specimens revealed significantly lower methylation levels in cancer compared to BPH at all enhancer sites analyzed (XRE-1383, XRE-983, XRE-895; P < 0.01). Interestingly, smoking affected the XRE-1383 site where the methylation level was much lower in cancer tissues from smokers than non-smokers (P < 0.05). CYP1A1 levels are thus increased in prostate cancer and to determine the functional effect of CYP1A1 on cells, we depleted the gene in LNCaP and DU145 by siRNA. We observe that CYP1A1 knockdown decreased cell proliferation (P < 0.05) and increased apoptosis (P < 0.01) in both cell lines. We analyzed genes affected by CYP1A1 silencing and found that apoptosis-related BCL2 was significantly down-regulated. This study supports an oncogenic role for CYP1A1 in prostate cancer via promoter hypomethylation that is influenced by tobacco smoking, indicating CYP1A1 to be a promising target for prostate cancer treatment. PMID:27203547

  9. Proton radiation for localized prostate cancer.

    PubMed

    Coen, John J; Zietman, Anthony L

    2009-06-01

    Proton radiation is an emerging therapy for localized prostate cancer that is being sought with increasing frequency by patients. The physical properties of a proton beam make it ideal for clinical applications; the Bragg peak allows for deposition of dose at a well-defined depth with essentially no exit dose. Thus, high doses can be delivered to a target while largely sparing adjacent normal tissue. Proton radiation has proven effective in dose escalation for prostate cancer. This is important, as high-dose conformal radiation is now the standard form of external radiation for this disease. Intensity-modulated radiation therapy, which uses X-rays, is another means of delivering high radiation doses to the prostate and is currently the most widely used form of external radiation in the US. At present prices, it is probably more cost-effective than proton radiation; this could change. Clear dosimetric superiority of protons in the high-dose region has not yet been demonstrated. A dosimetric advantage may emerge as pencil-beam scanning replaces passive scanning, and intensity-modulated proton therapy becomes possible. This technique would be particularly well suited to partial prostate 'boosts', hypofractionation regimens and stereotactic delivery of radiation, all new approaches to prostate cancer that are being investigated.

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

    PubMed

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

    2015-07-01

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

  11. Systematic Search for Gene-Gene Interaction Effect on Prostate Cancer Risk

    DTIC Science & Technology

    2012-07-01

    17q12 and 17q24.3 and prostate cancer risk in European and African Americans . Prostate, 68, 691-7. 15. Hsu, F.C., Sun, J., Wiklund, F., Isaacs, S.D...interact with the 32 known risk SNPs on PCa risk at a P- value of 1E-05 in the combined analysis of three populations. The most significant...patients and 1,157 control subjects of European Americans descent. The second study population is our large population-based case-control study from Sweden

  12. Linking obesogenic dysregulation to prostate cancer progression

    PubMed Central

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

    2015-01-01

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

  13. 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.

  14. [Hormonal therapy for prostatic cancer--state of the art].

    PubMed

    Miyakita, Hideshi

    2005-02-01

    Following the studies of Huggins and colleagues in 1941, the hormonal treatment of prostatic cancer has been aimed at neutralizing the influence of testicular androgens through surgical castration or the administration of high dose estrogen. Labrie et al introduced combined use of a LHRH agonist and an androgen antagonist for prostatic cancer. Various reports demonstrated a beneficial effect for combined androgen blockade using nonsteroidal antiandrogens for advanced prostatic cancer through meta-analysis of published randomized control trials. In Japanese status, a combined androgen blockade is popular for advanced prostatic cancer as well as local cancer by J-Cap survey. There is a lot of controversy about adjuvant hormonal therapy for prostatic cancer including intermittent hormonal therapy, but the results are not gotten yet.

  15. [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.

  16. 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

  17. Highly Stable PEGylated Poly(lactic-co-glycolic acid) (PLGA) Nanoparticles for the Effective Delivery of Docetaxel in Prostate Cancers

    NASA Astrophysics Data System (ADS)

    Cao, Long-Bin; Zeng, Sha; Zhao, Wei

    2016-06-01

    In the present study, a highly stable luteinizing-hormone-releasing hormone (LHRH)-conjugated PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles were developed for the successful treatment of prostate cancers. We have demonstrated that a unique combination of targeted drug delivery and controlled drug release is effective against prostate cancer therapy. The docetaxel (DTX)/PLGA-LHRH micelles possessed a uniform spherical shape with an average diameter of ~170 nm. The micelles exhibited a controlled drug release for up to 96 h which can minimize the non-specific systemic spread of toxic drugs during circulation while maximizing the efficiency of tumor-targeted drug delivery. The LHRH-conjugated micelles showed enhanced cellular uptake and exhibited significantly higher cytotoxicity against LNCaP cancer cells. We have showed that PLGA-LHRH induced greater caspase-3 activity indicating its superior apoptosis potential. Consistently, LHRH-conjugated micelles induced threefold and twofold higher G2/M phase arrest than compared to free DTX or PLGA NP-treated groups. Overall, results indicate that use of LHRH-conjugated nanocarriers may potentially be an effective nanocarrier to effectively treat prostate cancer.

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

    PubMed Central

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

    2013-01-01

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

  19. 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

  20. Cialis (Tadalafil) Does Not Prevent Erectile Dysfunction in Prostate Cancer Patients

    MedlinePlus

    ... Side Effects Study: Cialis (Tadalafil) Does Not Prevent Erectile Dysfunction in Prostate Cancer Patients Apr 4, 2014 Researchers ... that Cialis (tadalafil) does not help men avoid erectile dysfunction after radiation therapy for prostate cancer . Erection problems ...

  1. Dramatic remission of hormone refractory prostate cancer achieved with extract of the mushroom, Phellinus linteus.

    PubMed

    Shibata, Yasuhiro; Kurita, Susumu; Okugi, Hironobu; Yamanaka, Hidetoshi

    2004-01-01

    At present, there is no distinctly effective treatment for hormone refractory prostate cancer. We describe a hormone refractory prostate cancer patient with rapidly progressive bone metastasis who showed dramatic response to intake of an extract from the mushroom, Phellinus linteus.

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

    PubMed

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

    2011-12-01

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

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

    PubMed Central

    Barve, Ashutosh; Jin, Wei; Cheng, Kun

    2014-01-01

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

  4. Endocrine fibroblast growth factor FGF19 promotes prostate cancer progression.

    PubMed

    Feng, Shu; Dakhova, Olga; Creighton, Chad J; Ittmann, Michael

    2013-04-15

    Prostate cancer is the most common visceral malignancy and the second leading cause of cancer deaths in US men. There is broad evidence that fibroblast growth factor (FGF) receptors are important in prostate cancer initiation and progression, but the contribution of particular FGFs in this disease is not fully understood. The FGF family members FGF19, FGF21, and FGF23 comprise a distinct subfamily that circulate in serum and act in an endocrine manner. These endocrine FGFs require α-Klotho (KL) and/or β-Klotho (KLB), two related single-pass transmembrane proteins restricted in their tissue distribution, to act as coreceptors along with classic FGF receptors (FGFR) to mediate potent biologic activity. Here we show that FGF19 is expressed in primary and metastatic prostate cancer tissues, where it functions as an autocrine growth factor. Exogenous FGF19 promoted the growth, invasion, adhesion, and colony formation of prostate cancer cells at low ligand concentrations. FGF19 silencing in prostate cancer cells expressing autocrine FGF19 decreased invasion and proliferation in vitro and tumor growth in vivo. Consistent with these observations, KL and/or KLB were expressed in prostate cancer cells in vitro and in vivo, raising the possibility that additional endocrine FGFs may also exert biologic effects in prostate cancer. Our findings support the concept that therapies targeting FGFR signaling may have efficacy in prostate cancer and highlight FGF19 as a relevant endocrine FGF in this setting.

  5. Reconstructing the Prostate Cancer Transcriptional Regulatory Network

    DTIC Science & Technology

    2010-09-01

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

  6. Complementary and alternative medicine (CAM) in prostate and bladder cancer.

    PubMed

    Philippou, Yiannis; Hadjipavlou, Marios; Khan, Shahid; Rane, Abhay

    2013-12-01

    To provide an overview of the scientific and clinical studies underlying the most common vitamin and herbal preparations used in prostate and bladder cancer and evaluate the evidence behind them. A literature search was undertaken on PubMed using various keywords relating to the use of complementary and alternative medicine (CAM) in prostate and bladder cancer.Vitamin E and selenium supplementation can potentially have adverse effects by increasing the risk of prostate cancer. Initial clinical studies of pomegranate and green tea, investigating their chemotherapeutic properties in prostate and bladder cancer have yielded encouraging results. Curcumin, resveratrol, and silibinin have potential anticancer properties through multiple molecular targets; their clinical effectiveness in prostate and bladder cancer is yet to be evaluated. Zyflamend, like PC-SPES, is a combined CAM therapy used in prostate cancer. Acupuncture is popular among patients experiencing hot flushes who are receiving androgen-deprivation therapy for prostate cancer. Conclusive evidence for the use of CAM in prostate and bladder cancer is lacking and not without risk.

  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. CT-guided brachytherapy of prostate cancer: reduction of effective dose from X-ray examination

    NASA Astrophysics Data System (ADS)

    Sanin, Dmitriy B.; Biryukov, Vitaliy A.; Rusetskiy, Sergey S.; Sviridov, Pavel V.; Volodina, Tatiana V.

    2014-03-01

    Computed tomography (CT) is one of the most effective and informative diagnostic method. Though the number of CT scans among all radiographic procedures in the USA and European countries is 11% and 4% respectively, CT makes the highest contribution to the collective effective dose from all radiographic procedures, it is 67% in the USA and 40% in European countries [1-5]. Therefore it is necessary to understand the significance of dose value from CT imaging to a patient . Though CT dose from multiple scans and potential risk is of great concern in pediatric patients, this applies to adults as well. In this connection it is very important to develop optimal approaches to dose reduction and optimization of CT examination. International Commission on Radiological Protection (ICRP) in its publications recommends radiologists to be aware that often CT image quality is higher than it is necessary for diagnostic confidence[6], and there is a potential to reduce the dose which patient gets from CT examination [7]. In recent years many procedures, such as minimally invasive surgery, biopsy, brachytherapy and different types of ablation are carried out under guidance of computed tomography [6;7], and during a procedures multiple CT scans focusing on a specific anatomic region are performed. At the Clinics of MRRC different types of treatment for patients with prostate cancer are used, incuding conformal CT-guided brachytherapy, implantation of microsources of I into the gland under guidance of spiral CT [8]. So, the purpose of the study is to choose optimal method to reduce radiation dose from CT during CT-guided prostate brachytherapy and to obtain the image of desired quality.

  9. Apoptotic effect of demethoxyfumitremorgin C from marine fungus Aspergillus fumigatus on PC3 human prostate cancer cells.

    PubMed

    Kim, Young-Sang; Kim, Se-Kwon; Park, Sun Joo

    2017-03-28

    Demethoxyfumitremorgin C, a secondary metabolite of the marine fungus, Aspergillus fumigatus, had been reported to demonstrate cytotoxic effect on mouse tsFT210 cells. However, no information is available regarding its functional mechanism and the chemo-sensitization effects on different kinds of human cancer cells. We found that treatment of demethoxyfumitremorgin C inhibited the cell viability of PC3 human advanced prostate cancer cells, induced apoptosis as determined by Annexin V/propidium iodide double staining, and decreased mitochondrial membrane potential. Demethoxyfumitremorgin C induced apoptosis was associated with downregulation of anti-apoptotic proteins: Ras, PI3K, Akt, Bcl-xL, and Bcl-2, and upregulation of pro-apoptotic Bax. Demethoxyfumitremorgin C activated caspase-3, -8, and -9, leading to PARP cleavage. Additionally, caspase inhibitors blocked demethoxyfumitremorgin C-induced apoptosis of PC3 cells. These results suggest that demethoxyfumitremorgin C from Aspergillus fumigatus inhibits the proliferation of PC3 human prostate cancer cells via the intrinsic (mitochondrial) and extrinsic pathway, followed by downstream events leading to apoptotic cell death. Demethoxyfumitremorgin C could therefore, serve as a useful agent to treat human advanced prostate cancer.

  10. The epidemiology of prostate cancer.

    PubMed

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

    2003-05-01

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

  11. 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

  12. 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.

  13. Detection of aggressive prostate cancer associated glycoproteins in urine using glycoproteomics and mass spectrometry.

    PubMed

    Jia, Xingwang; Chen, Jing; Sun, Shisheng; Yang, Weiming; Yang, Shuang; Shah, Punit; Hoti, Naseruddin; Veltri, Bob; Zhang, Hui

    2016-12-01

    Clinical management of prostate cancer remains a significant challenge due to the lack of available tests for guiding treatment decisions. The blood prostate-specific antigen test has facilitated early detection and intervention of prostate cancer. However, blood prostate-specific antigen levels are less effective in distinguishing aggressive from indolent prostate cancers and other benign prostatic diseases. Thus, the development of novel approaches specific for prostate cancer that can differentiate aggressive from indolent disease remains an urgent medical need. In the current study, we evaluated urine specimens from prostate cancer patients using LC-MS/MS, with the aim of identifying effective urinary prostate cancer biomarkers. Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS. A total of 2923 unique glycosite-containing peptides were identified. Glycoproteomic comparison on urine and tissues from aggressive and non-aggressive prostate cancers as well as sera from prostate cancer patients revealed that the majority of AG prostate cancer associated glycoproteins were more readily detected in patient's urine than serum samples. Our data collectively indicate that urine provides a potential source for biomarker testing in patients with AG prostate cancer. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    PubMed Central

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

    2016-01-01

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

  15. Dietary Supplement 4-Methylumbelliferone: An Effective Chemopreventive and Therapeutic Agent for Prostate Cancer

    PubMed Central

    Yates, Travis J.; Lopez, Luis E.; Lokeshwar, Soum D.; Ortiz, Nicolas; Kallifatidis, Georgios; Jordan, Andre; Hoye, Kelly; Altman, Norman

    2015-01-01

    Background: Prevention and treatment of advanced prostate cancer (PCa) by a nontoxic agent can improve outcome, while maintaining quality of life. 4-methylumbelliferone (4-MU) is a dietary supplement that inhibits hyaluronic acid (HA) synthesis. We evaluated the chemopreventive and therapeutic efficacy and mechanism of action of 4-MU. Methods: TRAMP mice (7–28 per group) were gavaged with 4-MU (450mg/kg/day) in a stage-specific treatment design (8–28, 12–28, 22–28 weeks). Efficacy of 4-MU (200–450mg/kg/day) was also evaluated in the PC3-ML/Luc+ intracardiac injection and DU145 subcutaneous models. PCa cells and tissues were analyzed for HA and Phosphoinositide 3-kinase (PI-3K)/Akt signaling and apoptosis effectors. HA add-back and myristoylated Akt (mAkt) overexpression studies evaluated the mechanism of action of 4-MU. Data were analyzed with one-way analysis of variance and unpaired t test or Tukey’s multiple comparison test. All statistical tests were two-sided. Results: While vehicle-treated transgenic adenocarcinoma of the prostate (TRAMP) mice developed prostate tumors and metastases at 28 weeks, both were abrogated in treatment groups, without serum/organ toxicity or weight loss; no tumors developed at one year, even after stopping the treatment at 28 weeks. 4-MU did not alter the transgene or neuroendocrine marker expression but downregulated HA levels. However, 4-MU decreased microvessel density and proliferative index (P < .0001,). 4-MU completely prevented/inhibited skeletal metastasis in the PC3-ML/Luc+ model and DU145-tumor growth (85–90% inhibition, P = .002). 4-MU also statistically significantly downregulated HA receptors, PI-3K/CD44 complex and activity, Akt signaling, and β-catenin levels/activation, but upregulated GSK-3 function, E-cadherin, and apoptosis effectors (P < .001); HA addition or mAkt overexpression rescued these effects. Conclusion: 4-MU is an effective nontoxic, oral chemopreventive, and therapeutic agent that

  16. Stages of Prostate Cancer

    MedlinePlus

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

  17. A phase III clinical trial of exercise modalities on treatment side-effects in men receiving therapy for prostate cancer.

    PubMed

    Newton, Robert U; Taaffe, Dennis R; Spry, Nigel; Gardiner, Robert A; Levin, Gregory; Wall, Bradley; Joseph, David; Chambers, Suzanne K; Galvão, Daniel A

    2009-06-29

    Androgen deprivation therapy (ADT) is accompanied by a number of adverse side effects including reduced bone mass and increased risk for fracture, reduced lean mass and muscle strength, mood disturbance and increased fat mass compromising physical functioning, independence, and quality of life. The purpose of this investigation is to examine the effects of long term exercise on reversing musculoskeletal-related side effects, and cardiovascular and diabetes risk factors in men receiving androgen deprivation for their prostate cancer. Specifically, we aim to investigate the effects of a 12-month exercise program designed to load the musculoskeletal system and reduce cardiovascular and diabetes disease progression on the following primary endpoints: 1) bone mineral density; 2) cardiorespiratory function and maximal oxygen capacity; 3) body composition (lean mass and fat mass); 4) blood pressure and cardiovascular function; 5) lipids and glycemic control; and 6) quality of life and psychological distress. Multi-site randomized controlled trial of 195 men (65 subjects per arm) undergoing treatment for prostate cancer involving ADT in the cities of Perth and Brisbane in Australia. Participants will be randomized to (1) resistance/impact loading exercise, (2) resistance/cardiovascular exercise groups and (3) usual care/delayed exercise. Participants will then undergo progressive training for 12 months. Measurements for primary and secondary endpoints will take place at baseline, 6 and 12 months (end of the intervention). The principal outcome of this project will be the determination of the strength of effect of exercise on the well established musculoskeletal, cardiovascular and insulin metabolism side effects of androgen deprivation in prostate cancer patients. As this project is much longer term than previous investigations in the area of exercise and cancer, we will gain knowledge as to the continuing effects of exercise in this patient population specifically

  18. 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.

  19. Status of selenium in prostate cancer prevention

    PubMed Central

    Combs, G F

    2004-01-01

    The complete, 13 years, results of the Nutritional Prevention of Cancer Trial have been analysed, causing some speculation over the robustness of the previously reported findings of reduction of cancer risks by supplements of selenium (Se) to a cohort of older Americans. These analyses confirmed that Se supplementation was associated with marked reductions in risks to total (all-site except skin) carcinomas and to cancers of the prostate and colon–rectum. Of those deep-site treatment effects, the most robust was for prostate cancer, which was more frequent, and was confirmed by serum prostate-specific antigen level. Recent subgroup analyses showed Se supplementation reduced risk of cancer mostly among subjects who entered the trial with plasma Se levels in the bottom tertile of the cohort. Other recent findings have demonstrated that Se treatment can promote apoptosis in prostate cancer cells and, possibly, impair their proliferation through antiangiogenic effects. Thus, a body of basic understanding is developing by which one can understand and evaluate the results of the Nutritional Prevention of Cancer and future clinical trials. This understanding also requires inclusion of the mechanisms of Se transport and cellular uptake, so that appropriate inferences can be made from findings from cell culture systems, which tended to use effective Se doses much larger than relevant to cells in vivo. Also needed is information on the chemical speciation of Se in foods, so that Se delivery can be achieved in ways that are effective in reducing cancer risk and is also safe, accessible and sustainable. PMID:15213714

  20. The Effect of Metformin and GANT61 Combinations on the Radiosensitivity of Prostate Cancer Cells.

    PubMed

    Gonnissen, Annelies; Isebaert, Sofie; McKee, Chad M; Muschel, Ruth J; Haustermans, Karin

    2017-02-13

    The anti-diabetes drug metformin has been shown to have anti-neoplastic effects in several tumor models through its effects on energy metabolism and protein synthesis. Recent studies show that metformin also targets Hedgehog (Hh) signaling, a developmental pathway re-activated in several tumor types, including prostate cancer (PCa). Furthermore, we and others have shown that Hh signaling is an important target for radiosensitization. Here, we evaluated the combination of metformin and the Hh inhibitor GANT61 (GLI-ANTagonist 61) with or without ionizing radiation in three PCa cell lines (PC3, DU145, 22Rv1). The effect on proliferation, radiosensitivity, apoptosis, cell cycle distribution, reactive oxygen species production, DNA repair, gene and protein expression was investigated. Furthermore, this treatment combination was also assessed in vivo. Metformin was shown to interact with Hh signaling by inhibiting the effector protein glioma-associated oncogene homolog 1 (GLI1) in PCa cells both in vitro and in vivo. The combination of metformin and GANT61 significantly inhibited PCa cell growth in vitro and enhanced the radiation response of 22Rv1 cells compared to either single agent. Nevertheless, neither the growth inhibitory effect nor the radiosensitization effect of the combination treatment observed in vitro was seen in vivo. Although the interaction between metformin and Hh signaling seems to be promising from a therapeutic point of view in vitro, more research is needed when implementing this combination strategy in vivo.

  1. The Effect of Metformin and GANT61 Combinations on the Radiosensitivity of Prostate Cancer Cells

    PubMed Central

    Gonnissen, Annelies; Isebaert, Sofie; McKee, Chad M.; Muschel, Ruth J.; Haustermans, Karin

    2017-01-01

    The anti-diabetes drug metformin has been shown to have anti-neoplastic effects in several tumor models through its effects on energy metabolism and protein synthesis. Recent studies show that metformin also targets Hedgehog (Hh) signaling, a developmental pathway re-activated in several tumor types, including prostate cancer (PCa). Furthermore, we and others have shown that Hh signaling is an important target for radiosensitization. Here, we evaluated the combination of metformin and the Hh inhibitor GANT61 (GLI-ANTagonist 61) with or without ionizing radiation in three PCa cell lines (PC3, DU145, 22Rv1). The effect on proliferation, radiosensitivity, apoptosis, cell cycle distribution, reactive oxygen species production, DNA repair, gene and protein expression was investigated. Furthermore, this treatment combination was also assessed in vivo. Metformin was shown to interact with Hh signaling by inhibiting the effector protein glioma-associated oncogene homolog 1 (GLI1) in PCa cells both in vitro and in vivo. The combination of metformin and GANT61 significantly inhibited PCa cell growth in vitro and enhanced the radiation response of 22Rv1 cells compared to either single agent. Nevertheless, neither the growth inhibitory effect nor the radiosensitization effect of the combination treatment observed in vitro was seen in vivo. Although the interaction between metformin and Hh signaling seems to be promising from a therapeutic point of view in vitro, more research is needed when implementing this combination strategy in vivo. PMID:28208838

  2. Effect of anatomic motion on proton therapy dose distributions in prostate cancer treatment

    SciTech Connect

    Zhang Xiaodong . E-mail: xizhang@mdanderson.org; Dong, Lei; Lee, Andrew K.; Cox, James D.; Kuban, Deborah A.; Zhu, Ron X.; Wang Xiaochun; Li Yupeng; Newhauser, Wayne D.; Gillin, Michael; Mohan, Radhe

    2007-02-01

    Purpose: To determine the dosimetric impact of interfraction anatomic movements in prostate cancer patients receiving proton therapy. Methods and Materials: For each of the 10 patients studied, 8 computed tomography (CT) scans were selected from sets of daily setup CT images that were acquired from a cohort of prostate cancer patients. The images were acquired in the treatment room using the CT-on-rails system. First, standard proton therapy and intensity-modulated radiation therapy (IMRT) plans were designed for each patient using standard modality-specific methods. The images, the proton plan, and the IMRT plan were then aligned to the eight CT images based on skin marks. The doses were recalculated on these eight CT images using beam from the standard plans. Second, the plans were redesigned and evaluated assuming a smaller clinical target volume to planning target volume margin (3 mm). The images and the corresponding plans were then realigned based on the center of volume of the prostate. Dose distributions were evaluated using isodose displays, dose-volume histograms, and target coverage. Results: For the skin-marker alignment method, 4 of the 10 IMRT plans were deficient, whereas 3 of 10 proton plans were compromised. For the alignment method based on the center of volume of the prostate, only the proton plan for 1 patient was deficient, whereas 3 of the 10 IMRT plans were suboptimal. Conclusion: A comparison of passively scattered proton therapy and highly conformal IMRT plans for prostate cancer revealed that the dosimetric impact of interfractional anatomic motions was similar for both modalities.

  3. Prostate cancer and inflammation: the evidence

    PubMed Central

    Sfanos, Karen S; De Marzo, Angelo M

    2014-01-01

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

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

    PubMed

    Cheetham, Philippa J; Katz, Aaron E

    2011-10-01

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

  5. Transcriptional network of androgen receptor in prostate cancer progression.

    PubMed

    Takayama, Ken-ichi; Inoue, Satoshi

    2013-08-01

    The androgen receptor belongs to the nuclear receptor superfamily and functions as a ligand-dependent transcription factor. It binds to the androgen responsive element and recruits coregulatory factors to modulate gene transcription. In addition, the androgen receptor interacts with other transcription factors, such as forkhead box A1, and other oncogenic signaling pathway molecules that bind deoxyribonucleic acid and regulate transcription. Androgen receptor signaling plays an important role in the development of prostate cancer. Prostate cancer cells proliferate in an androgen-dependent manner, and androgen receptor blockade is effective in prostate cancer therapy. However, patients often progress to castration-resistant prostate cancer with elevated androgen receptor expression and hypersensitivity to androgen. Recently, comprehensive analysis tools, such as complementary DNA microarray, chromatin immunoprecipitation-on-chip and chromatin immunoprecipitation-sequence, have described the androgen-mediated diverse transcriptional program and gene networks in prostate cancer. Furthermore, functional and clinical studies have shown that some of the androgen receptor-regulated genes could be prognostic markers and potential therapeutic targets for the treatment of prostate cancer, particularly castration-resistant prostate cancer. Thus, identifying androgen receptor downstream signaling events and investigating the regulation of androgen receptor activity is critical for understanding the mechanism of carcinogenesis and progression to castration-resistant prostate cancer.

  6. Gonadotrophin releasing hormone-based vaccine, an effective candidate for prostate cancer and other hormone-sensitive neoplasms.

    PubMed

    Junco, Jesús A; Basalto, Roberto; Fuentes, Franklin; Bover, Eddy; Reyes, Osvaldo; Pimentel, Eulogio; Calzada, Lesvia; Castro, Maria D; Arteaga, Niurka; López, Yovisleidis; Hernández, Héctor; Bringas, Ricardo; Garay, Hilda; Peschke, Peter; Bertot, José; Guillén, Gerardo

    2008-01-01

    Prostate growth, development, functions, and neoplastic transformation is androgen dependent. Estrogens have similar effects in the ovary and breast. Previous studies using gonadotrophin releasing hormone (GnRH/LHRH) vaccines have shown the usefulness of immunization against this hormone in prostate (PC) and breast cancer (BC). We have synthesized a peptide mutated at position 6 and attached to the 830-844 tetanic toxoid (TT) helper T cell sequence in the same synthesis process. After repeated pig immunizations, we have demonstrated a vaccine that significantly decreased testes size (p < 0.001), prostate (p < 0.01), seminal vesicles (p < 0.01), and testosterone (T) castration [0.05 nM ml(-1) (p < 0. 01)]. Similar results were obtained in adult male and female healthy dogs and Macaca fascicularis models. These data indicate that this GnRHm1-TT vaccine is safe and able to induce significant tumor growth inhibition in the Dunning R3327-H rat androgen responsive prostate tumor model. In these rats, the immunization induced high anti-GnRH titers concomitant with T castration reduction (p < 0.01) in 90% of the animals tested. In addition, 70% of the responders exhibited tumor growth inhibition (p = 0.02) and a survival rate approximately three times longer that those of untreated rats. These data indicate that GnRHm1-TT vaccine may be a potential candidate in the treatment of PC, BC, and other hormone-dependent cancers.

  7. Targeting amino acid transport in metastatic castration-resistant prostate cancer: effects on cell cycle, cell growth, and tumor development.

    PubMed

    Wang, Qian; Tiffen, Jessamy; Bailey, Charles G; Lehman, Melanie L; Ritchie, William; Fazli, Ladan; Metierre, Cynthia; Feng, Yue Julie; Li, Estelle; Gleave, Martin; Buchanan, Grant; Nelson, Colleen C; Rasko, John E J; Holst, Jeff

    2013-10-02

    L-type amino acid transporters (LATs) uptake neutral amino acids including L-leucine into cells, stimulating mammalian target of rapamycin complex 1 signaling and protein synthesis. LAT1 and LAT3 are overexpressed at different stages of prostate cancer, and they are responsible for increasing nutrients and stimulating cell growth. We examined LAT3 protein expression in human prostate cancer tissue microarrays. LAT function was inhibited using a leucine analog (BCH) in androgen-dependent and -independent environments, with gene expression analyzed by microarray. A PC-3 xenograft mouse model was used to study the effects of inhibiting LAT1 and LAT3 expression. Results were analyzed with the Mann-Whitney U or Fisher exact tests. All statistical tests were two-sided. LAT3 protein was expressed at all stages of prostate cancer, with a statistically significant decrease in expression after 4-7 months of neoadjuvant hormone therapy (4-7 month mean = 1.571; 95% confidence interval = 1.155 to 1.987 vs 0 month = 2.098; 95% confidence interval = 1.962 to 2.235; P = .0187). Inhibition of LAT function led to activating transcription factor 4-mediated upregulation of amino acid transporters including ASCT1, ASCT2, and 4F2hc, all of which were also regulated via the androgen receptor. LAT inhibition suppressed M-phase cell cycle genes regulated by E2F family transcription factors including critical castration-resistant prostate cancer regulatory genes UBE2C, CDC20, and CDK1. In silico analysis of BCH-downregulated genes showed that 90.9% are statistically significantly upregulated in metastatic castration-resistant prostate cancer. Finally, LAT1 or LAT3 knockdown in xenografts inhibited tumor growth, cell cycle progression, and spontaneous metastasis in vivo. Inhibition of LAT transporters may provide a novel therapeutic target in metastatic castration-resistant prostate cancer, via suppression of mammalian target of rapamycin complex 1 activity and M-phase cell cycle genes.

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

    PubMed

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

    2017-02-01

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

  9. Soy Isoflavones Exert Differential Effects on Androgen Responsive Genes in LNCaP Human Prostate Cancer Cells1

    PubMed Central

    Rice, Lori; Handayani, Renita; Cui, Yuehua; Medrano, Theresa; Samedi, Von; Baker, Henry; Szabo, Nancy J.; Rosser, Charles J.; Goodison, Steve; Shiverick, Kathleen T.

    2007-01-01

    The high consumption of soy isoflavones in Asian diets has been correlated to a lower incidence of clinically important cases of prostate cancer. This study characterized the effects of a soy-derived isoflavone concentrate (ISF) on growth and gene expression profiles in the LNCaP, an androgen-sensitive human prostate cancer cell line. ISF caused a dose-dependent decrease in viability (P<0.05) and DNA synthesis (P<0.01), as well as an accumulation of cells in G2/M, and G0/G1 phases of the cell cycle compared with controls. Using Affymetrix oligonucleotide DNA microarrays (U133A), we determined that ISF upregulated 80 genes and downregulated 33 genes (P<0.05) involving androgen-regulated genes and pathways controlling cell cycle, metabolism, and intracellular trafficking. Changes in the expression of the genes of interest, identified by microarrays, were validated by Western immunoblot, Northern blot, and luciferase reporter assays. Prostate-specific antigen, homeobox protein NKX3, and cyclin B mRNA were significantly reduced, whereas mRNA was significantly upregulated for p21CIP1, a major cell cycle inhibitory protein, and fatty acid and cholesterol synthesis pathway genes. ISF also significantly increased cyclin-dependent kinase inhibitor p27KIP1 and FOXO3A/FKHRL1, a forkhead transcription factor. A differential pattern of androgen-regulated genes was apparent with genes involved in prostate cancer progression being downregulated by ISF, whereas metabolism genes were upregulated. In summary, we found that ISF inhibits the growth of LNCaP cells through the modulation of cell cycle progression and the differential expression of androgen-regulated genes. Thus, ISF treatment serves to identify new therapeutic targets designed to prevent proliferation of malignant prostate cells. PMID:17374662

  10. Vaccine Immunotherapy for Prostate Cancer

    DTIC Science & Technology

    2010-05-01

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

  11. Methylselenium and Prostate Cancer Apoptosis

    DTIC Science & Technology

    2008-02-01

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

  12. [Inhibitory effect of Genipin on uncoupling protein-2 and energy metabolism of androgen-independent prostate cancer cells].

    PubMed

    Yao, Mao-liang; Gu, Jiang; Zhang, Yong-chun; Wang, Nan; Zhu, Zhi-hui; Yang, Qing-tao; Liu, Miao; Xia, Jian-feng

    2015-11-01

    To explore whether the inhibitory effect of Genipin on uncoupling protein-2 (UCP-2) in mitochondria is involved in energy metabolism of androgen-independent PC3 prostate cancer cells. PC3 prostate cancer cells were cultured and treated with Genipin at the concentrations of 40, 80, and 160 μmol/L for 48 hours. Then the proliferation of the cells was detected by MTT assay, the expression of UCP-2 mRNA determined by RT-PCR, and the content of intracellular pyruvic acid (PA) and the activity of succinate dehydrogenase (SDH) in the mitochondria measured by visible spectrophotometry. With the increased concentration of Genipin, the proliferative activity of the PC-3 cells, the expression level of UCP-2 mRNA, the content of intracellular PA and the activity of SDH in the cells were all decreased, namely, with the enhanced inhibitory effect of Genipin on UCP-2, a trend of reduction was observed in the proliferation of the cells, intracellular PA content, and SDH activity in the mitochondria. Genipin is involved in the energy metabolism of androgen-independent PC3 prostate cancer cells by reducing the content of intracellular PA and the activity of SDH in the mitochondria, which may be associated with its inhibitory effect on UCP-2.

  13. Heparin affin regulatory peptide/pleiotrophin mediates fibroblast growth factor 2 stimulatory effects on human prostate cancer cells.

    PubMed

    Hatziapostolou, Maria; Polytarchou, Christos; Katsoris, Panagiotis; Courty, Jose; Papadimitriou, Evangelia

    2006-10-27

    Fibroblast growth factor 2 (FGF2) is a pleiotropic growth factor that has been implicated in prostate cancer formation and progression. In the present study we found that exogenous FGF2 significantly increased human prostate cancer LNCaP cell proliferation and migration. Heparin affin regulatory peptide (HARP) or pleiotrophin seems to be an important mediator of FGF2 stimulatory effects, since the latter had no effect on stably transfected LNCaP cells that did not express HARP. Moreover, FGF2, through FGF receptors (FGFRs), significantly induced HARP expression and secretion by LNCaP cells and increased luciferase activity of a reporter gene vector carrying the full-length promoter of HARP gene. Using a combination of Western blot analyses, as well as genetic and pharmacological inhibitors, we found that activation of FGFR by FGF2 in LNCaP cells leads to NAD(P)H oxidase-dependent hydrogen peroxide production, phosphorylation of ERK1/2 and p38, activation of AP-1, increased expression and secretion of HARP, and, finally, increased cell proliferation and migration. These results establish the role and the mode of activity of FGF2 in LNCaP cells and support an interventional role of HARP in FGF2 effects, providing new insights on the interplay among growth factor pathways within prostate cancer cells.

  14. [Current treatments of cancer of the prostate].

    PubMed

    Saussine, C; Bollack, C

    1991-10-19

    Cancer of the prostate mainly occurs in elderly men and is becoming more frequent as the general European population gets older. Only through continuing progress in the already well developed therapeutic methods will mortality due to this cancer be curtailed. Prognosis of cancer limited to the prostate gland has been improved by radical surgery which reduces morbidity and mortality and advanced radiotherapy techniques. The potentially curable forms, still mainly detected by systematic rectal examination, can be defined better with magnetic resonance imagery and biological markers. Hormonal treatment for more extended or metastatic cancers is now based on several effective, well tolerated products. Chemotherapy has not been able to solve the problem of hormonal escape for which other therapeutic techniques are now under study.

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

    PubMed

    Chen, RuiQi; Yu, Yue; Dong, Xuesen

    2017-02-01

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

  16. Boron intake and prostate cancer risk.

    PubMed

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

    2007-12-01

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

  17. Prostate Cancer Research Training Program

    DTIC Science & Technology

    2014-04-01

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

  18. 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.

  19. Baseline selenium status and effects of selenium and vitamin e supplementation on prostate cancer risk.

    PubMed

    Kristal, Alan R; Darke, Amy K; Morris, J Steven; Tangen, Catherine M; Goodman, Phyllis J; Thompson, Ian M; Meyskens, Frank L; Goodman, Gary E; Minasian, Lori M; Parnes, Howard L; Lippman, Scott M; Klein, Eric A

    2014-03-01

    The Selenium and Vitamin E Cancer Prevention Trial found no effect of selenium supplementation on prostate cancer (PCa) risk but a 17% increased risk from vitamin E supplementation. This case-cohort study investigates effects of selenium and vitamin E supplementation conditional upon baseline selenium status. There were 1739 total and 489 high-grade (Gleason 7-10) PCa cases and 3117 men in the randomly selected cohort. Proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for effects of supplementation within quintiles of baseline toenail selenium. Cox proportional hazards models were used to estimate hazard ratios, and all statistical tests are two-sided. Toenail selenium, in the absence of supplementation, was not associated with PCa risk. Selenium supplementation (combined selenium only and selenium + vitamin E arms) had no effect among men with low selenium status (<60th percentile of toenail selenium) but increased the risk of high-grade PCa among men with higher selenium status by 91% (P = .007). Vitamin E supplementation (alone) had no effect among men with high selenium status (≥40th percentile of toenail selenium) but increased the risks of total, low-grade, and high-grade PCa among men with lower selenium status (63%, P = .02; 46%, P = .09; 111%, P = .008, respectively). Selenium supplementation did not benefit men with low selenium status but increased the risk of high-grade PCa among men with high selenium status. Vitamin E increased the risk of PCa among men with low selenium status. Men should avoid selenium or vitamin E supplementation at doses that exceed recommended dietary intakes.

  20. The Thoc1 ribonucleoprotein and prostate cancer progression.

    PubMed

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

    2014-11-01

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

  1. Differential effects of cholesterol and phytosterols on cell proliferation, apoptosis and expression of a prostate specific gene in prostate cancer cell lines.

    PubMed

    Ifere, Godwin O; Barr, Erika; Equan, Anita; Gordon, Kereen; Singh, Udai P; Chaudhary, Jaideep; Igietseme, Joseph U; Ananaba, Godwin A

    2009-01-01

    The purpose of our study was to show the apoptotic and anti-proliferative effects of phytosterols as distinct from cholesterol effects on prostate cancer cell lines, and also their differential expression of caveolin-1, and a prostate specific gene, PCGEM1. PC-3 and DU145 cells were treated with sterols (cholesterol and phytosterols) for 48h, followed by trypan blue dye exclusion measurement of cytotoxicity and MTT cell proliferation assays, respectively. Cell cycle analysis was carried out microscopically, and by propidium iodide uptake using flow cytometry. Sterol induction of oncogenic gene expression was evaluated by RT-PCR. Apoptotic cells were identified by immunocytochemistry using DNA fragmentation method, and by annexin V adhesion using flow cytometry. Physiological doses (16microM) of these sterols were not cytotoxic in these cells. Cholesterol-enrichment promoted mitosis (54 and 61% by microscopy; 40.8 and 34.08% by FACS analysis in PC-3 and DU145, respectively) and cell growth (P<0.05), while phytosterols suppressed mitosis (29 and 35% by microscopy; 27.71 and 17.37% by FACS analysis in PC-3 and DU145, respectively), and significantly induced tumor-suppression (P<0.05) and apoptosis. We demonstrated for the first time that cholesterols upregulated the expression of PCGEM1 even in androgen-insensitive prostate cancer cell lines. Phytosterols reversed this effect, while upregulating the expression of caveolin-1, a known mediator of androgen-dependent proto-oncogene signals that presumably control growth and anti-apoptosis. Phytosterol inhibition of PCGEM1 and cell growth and the overexpression of caveolin-1, suggests that poor disease prognosis anchors on the ability of caveolin-1 to regulate downstream oncogene(s) and apoptosis genes. Sterol intake may contribute to the disparity in incidence of prostate cancer, and elucidation of the mechanism for modulation of growth and apoptosis signaling may reveal potential targets for cancer prevention and

  2. Inhibition of hedgehog signaling improves the anti-carcinogenic effects of docetaxel in prostate cancer.

    PubMed

    Mimeault, Murielle; Rachagani, Satyanarayana; Muniyan, Sakthivel; Seshacharyulu, Parthasarathy; Johansson, Sonny L; Datta, Kaustubh; Lin, Ming-Fong; Batra, Surinder K

    2015-02-28

    The establishment of docetaxel-based chemotherapeutic treatments has improved the survival of castration-resistant prostate cancer (CRPC) patients. However, most patients develop resistance supporting the development of therapy. The current study was undertaken to establish the therapeutic benefit to target hedgehog signaling cascade using GDC-0449 to improve the efficacy of chemotherapeutic drug, docetaxel. Here, we show that the combination of GDC-0449 plus docetaxel inhibited the proliferation of WPE1-NB26 cells and PC3 cells via a blockade of G1 and G2M phases. The combined treatment significantly inhibited PC cell migration in vitro. Moreover, the apoptotic effect induced by GDC-0449 plus docetaxel on PC3 cells was mediated, at least partly, via the mitochondrial membrane depolarization, H2O2 production and caspase cascade activation. Interestingly, GDC-0449 was effective at inhibiting the prostasphere formation, inducing the prostasphere disintegration and apoptotic death of side population (SP) from PC3 cells and reversing the resistance of SP cells to docetaxel. In addition, GDC-0449 plus docetaxel also have shown a greater anti-tumoral growth inhibitory effect on PC3 cell xenografts. These findings support the use of the hedgehog inhibitor GDC-0449, which is currently in clinical trials, for improving the anticarcinogenic efficacy of docetaxel-based chemotherapeutic treatments against locally advanced, AI and metastatic PC.

  3. Differential Effects of Genistein on Prostate Cancer Cells Depend on Mutational Status of the Androgen Receptor

    PubMed Central

    Mahmoud, Abeer M.; Zhu, Tian; Parray, Aijaz; Siddique, Hifzur R.; Yang, Wancai; Saleem, Mohammad; Bosland, Maarten C.

    2013-01-01

    Blocking the androgen receptor (AR) activity is the main goal of therapies for advanced prostate cancer (PCa). However, relapse with a more aggressive, hormone refractory PCa arises, which harbors restored AR activity. One mechanism of such reactivation occurs through acquisition of AR mutations that enable its activation by various steroidal and non-steroidal structures. Thus, natural and chemical compounds that contribute to inappropriate (androgen-independent) activation of the AR become an area of intensive research. Here, we demonstrate that genistein, a soy phytoestrogen binds to both the wild and the Thr877Ala (T877A) mutant types of AR competitively with androgen, nevertheless, it exerts a pleiotropic effect on PCa cell proliferation and AR activity depending on the mutational status of the AR. Genistein inhibited, in a dose-dependent way, cell proliferation and AR nuclear localization and expression in LAPC-4 cells that have wild AR. However, in LNCaP cells that express the T877A mutant AR, genistein induced a biphasic effect where physiological doses (0.5-5 µmol/L) stimulated cell growth and increased AR expression and transcriptional activity, and higher doses induced inhibitory effects. Similar biphasic results were achieved in PC-3 cells transfected with AR mutants; T877A, W741C and H874Y. These findings suggest that genistein, at physiological concentrations, potentially act as an agonist and activate the mutant AR that can be present in advanced PCa after androgen ablation therapy. PMID:24167630

  4. Differential effects of genistein on prostate cancer cells depend on mutational status of the androgen receptor.

    PubMed

    Mahmoud, Abeer M; Zhu, Tian; Parray, Aijaz; Siddique, Hifzur R; Yang, Wancai; Saleem, Mohammad; Bosland, Maarten C

    2013-01-01

    Blocking the androgen receptor (AR) activity is the main goal of therapies for advanced prostate cancer (PCa). However, relapse with a more aggressive, hormone refractory PCa arises, which harbors restored AR activity. One mechanism of such reactivation occurs through acquisition of AR mutations that enable its activation by various steroidal and non-steroidal structures. Thus, natural and chemical compounds that contribute to inappropriate (androgen-independent) activation of the AR become an area of intensive research. Here, we demonstrate that genistein, a soy phytoestrogen binds to both the wild and the Thr877Ala (T877A) mutant types of AR competitively with androgen, nevertheless, it exerts a pleiotropic effect on PCa cell proliferation and AR activity depending on the mutational status of the AR. Genistein inhibited, in a dose-dependent way, cell proliferation and AR nuclear localization and expression in LAPC-4 cells that have wild AR. However, in LNCaP cells that express the T877A mutant AR, genistein induced a biphasic effect where physiological doses (0.5-5 µmol/L) stimulated cell growth and increased AR expression and transcriptional activity, and higher doses induced inhibitory effects. Similar biphasic results were achieved in PC-3 cells transfected with AR mutants; T877A, W741C and H874Y. These findings suggest that genistein, at physiological concentrations, potentially act as an agonist and activate the mutant AR that can be present in advanced PCa after androgen ablation therapy.

  5. 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

  6. 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 ...

  7. Effect of Practice Integration between Urologists and Radiation Oncologists on Prostate Cancer Treatment Patterns

    PubMed Central

    Bekelman, Justin E.; Suneja, Gita; Guzzo, Thomas; Evan Pollack, Craig; Armstrong, Katrina; Epstein, Andrew J.

    2013-01-01

    Purpose National attention has focused on whether urology-radiation oncology practice integration – known as integrated prostate cancer centers (IPCCs) – contributes to use of intensity-modulated radiation therapy (IMRT), a common and expensive treatment for prostate cancer. Methods We examined prostate cancer treatment patterns pre- and post-conversion of a urology practice to an IPCC in July, 2006. Using the SEER-Medicare database, we identified patients age ≥ 65 years diagnosed in one state-wide registry with non-metastatic prostate cancer between 2004 and 2007 and classified patients into 3 groups: (1) those seen by IPCC physicians (exposure group); (2) those living in the same hospital referral region (HRR) and not seen by IPCC physicians (HRR-control group); and (3) those living elsewhere in the state (state-control group). We compared changes in treatment among the 3 groups, adjusting for patient, clinical, and socio-economic factors. Results Compared with the 8.1 percentage point (ppt) increase in adjusted IMRT use in the state-control group, IMRT increased 20.3 ppts (95% confidence interval [CI] 13.4, 27.1) in the IPCC group and 19.2 ppts (95% CI 9.6, 28.9) in the HRR-control group. Androgen-deprivation therapy (ADT), for which Medicare reimbursement declined sharply, decreased similarly in the IPCC and HRR-control groups. Prostatectomy declined significantly in the IPCC group. Conclusions Coincident with the conversion of a urology group practice to an IPCC, we observed increases in IMRT and decreases in ADT among patients seen by IPCC physicians and those seen in the surrounding healthcare market that were not observed in the remainder of the state. PMID:23399652

  8. Comparative Effectiveness Study of Patient-Reported Outcomes following Proton Therapy or IMRT for Prostate Cancer

    PubMed Central

    Hoppe, Bradford S.; Michalski, Jeff M.; Mendenhall, Nancy P.; Morris, Christopher G.; Henderson, Randal H.; Nichols, Romaine C.; Mendenhall, William M.; Williams, Christopher; Regan, Meredith M.; Chipman, Jonathan; Crociani, Catrina; Sandler, Howard M.; Sanda, Martin G.; Hamstra, Daniel A.

    2014-01-01

    Background Data continues to emerge on the relative merits of different treatment modalities for prostate cancer. The purpose of this study is to compare patient-reported quality-of-life outcomes (QOL) after proton therapy (PT) and intensity-modulated radiation therapy (IMRT) for prostate cancer. Methods A comparison was performed of prospectively collected QOL data using the expanded prostate cancer index (EPIC) questionnaire. QOL data was collected during the first 2 years following treatment for men treated with PT and IMRT. PT was delivered to 1,243 men at a single center to 76-82Gy. IMRT was delivered to 204 men included in the Prostate Cancer Quality Assurance Study (PROSTQA) in doses of 75.6-79.4Gy.The Wilcoxon rank sum test was used to compare EPIC outcomes by modality using baseline-adjusted scores at different time points. Individual questions were assessed by converting to binary outcomes and testing with generalized estimating equations. Results No differences in changes in summary scores for bowel, urinary incontinence, urinary irritative/obstructive, and sexual domains were seen between the two cohorts. However, more men treated with IMRT reported moderate/big problems with rectal urgency (p=0.02) and frequent bowel movements (p=0.05) than men treated with PT. Conclusions There were no differences in QOL summary scores between the IMRT and PT cohorts during early follow-up up to 2-years. Response to individual questions suggests possible differences in specific bowel symptoms between the two cohorts. These outcomes highlight the need for further comparative studies of PT and IMRT. PMID:24382757

  9. Retrovirally transduced murine T lymphocytes expressing FasL mediate effective killing of prostate cancer cells

    PubMed Central

    Symes, JC; Siatskas, C; Fowler, DH; Medin, JA

    2010-01-01

    Adoptively transferred T cells possess anticancer activities partially mediated by T-cell FasL engagement of Fas tumor targets. However, antigen-induced T-cell activation and clonal expansion, which stimulates FasL activity, is often inefficient in tumors. As a gene therapy approach to overcome this obstacle, we have created oncoretroviral vectors to overexpress FasL or non-cleavable FasL (ncFasL) on murine T cells of a diverse T-cell receptor repertoire. Expression of c-FLIP was also engineered to prevent apoptosis of transduced cells. Retroviral transduction of murine T lymphocytes has historically been problematic, and we describe optimized T-cell transduction protocols involving CD3/CD28 co-stimulation of T cells, transduction on ice using concentrated oncoretrovirus, and culture with IL-15. Genetically modified T cells home to established prostate cancer tumors in vivo. Co-stimulated T cells expressing FasL, ncFasL and ncFasL/c-FLIP each mediated cytotoxicity in vitro against RM-1 and LNCaP prostate cancer cells. To evaluate the compatibility of this approach with current prostate cancer therapies, we exposed RM-1, LNCaP, and TRAMP-C1 cells to radiation, mitoxantrone, or docetaxel. Fas and H-2b expression were upregulated by these methods. We have developed a novel FasL-based immuno-gene therapy for prostate cancer that warrants further investigation given the apparent constitutive and inducible Fas pathway expression in this malignancy. PMID:19096446

  10. Effects of Calorie Restriction and IGF-1 Receptor Blockade on the Progression of 22Rv1 Prostate Cancer Xenografts

    PubMed Central

    Galet, Colette; Gray, Ashley; Said, Jonathan W.; Castor, Brandon; Wan, Junxiang; Beltran, Pedro J.; Calzone, Franck J.; Elashoff, David; Cohen, Pinchas; Aronson, William J.

    2013-01-01

    Calorie restriction (CR) inhibits prostate cancer progression, partially through modulation of the IGF axis. IGF-1 receptor (IGF-1R) blockade reduces prostate cancer xenograft growth. We hypothesized that combining calorie restriction with IGF-1R blockade would have an additive effect on prostate cancer growth. Severe combined immunodeficient mice were subcutaneously injected with 22Rv1 cells and randomized to: (1) Ad libitum feeding/intraperitoneal saline (Ad-lib); (2) Ad-lib/20 mg/kg twice weekly, intraperitoneal ganitumab [anti-IGF-1R antibody (Ad-lib/Ab)]; (3) 40% calorie restriction/intraperitoneal saline (CR); (4) CR/ intraperitoneal ganitumab, (CR/Ab). CR and ganitumab treatment were initiated one week after tumor injection. Euthanasia occurred 19 days post treatment. Results showed that CR alone decreased final tumor weight, plasma insulin and IGF-1 levels, and increased apoptosis. Ganitumab therapy alone reduced tumor growth but had no effect on final tumor weight. The combination therapy (CR/Ab) further decreased final tumor weight and proliferation, increased apoptosis in comparison to the Ad-lib group, and lowered plasma insulin levels relative to the Ad-lib and Ad-lib/Ab groups. Tumor AKT activation directly correlated with plasma IGF-1 levels. In conclusion, whereas ganitumab therapy modestly affected 22Rv1 tumor growth, combining IGF-1R blockade with calorie restriction resulted in a significant decrease in final tumor weight and improved metabolic profile. PMID:23823800

  11. Effects of calorie restriction and IGF-1 receptor blockade on the progression of 22Rv1 prostate cancer xenografts.

    PubMed

    Galet, Colette; Gray, Ashley; Said, Jonathan W; Castor, Brandon; Wan, Junxiang; Beltran, Pedro J; Calzone, Franck J; Elashoff, David; Cohen, Pinchas; Aronson, William J

    2013-07-03

    Calorie restriction (CR) inhibits prostate cancer progression, partially through modulation of the IGF axis. IGF-1 receptor (IGF-1R) blockade reduces prostate cancer xenograft growth. We hypothesized that combining calorie restriction with IGF-1R blockade would have an additive effect on prostate cancer growth. Severe combined immunodeficient mice were subcutaneously injected with 22Rv1 cells and randomized to: (1) Ad libitum feeding/intraperitoneal saline (Ad-lib); (2) Ad-lib/20 mg/kg twice weekly, intraperitoneal ganitumab [anti-IGF-1R antibody (Ad-lib/Ab)]; (3) 40% calorie restriction/intraperitoneal saline (CR); (4) CR/ intraperitoneal ganitumab, (CR/Ab). CR and ganitumab treatment were initiated one week after tumor injection. Euthanasia occurred 19 days post treatment. Results showed that CR alone decreased final tumor weight, plasma insulin and IGF-1 levels, and increased apoptosis. Ganitumab therapy alone reduced tumor growth but had no effect on final tumor weight. The combination therapy (CR/Ab) further decreased final tumor weight and proliferation, increased apoptosis in comparison to the Ad-lib group, and lowered plasma insulin levels relative to the Ad-lib and Ad-lib/Ab groups. Tumor AKT activation directly correlated with plasma IGF-1 levels. In conclusion, whereas ganitumab therapy modestly affected 22Rv1 tumor growth, combining IGF-1R blockade with calorie restriction resulted in a significant decrease in final tumor weight and improved metabolic profile.

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

    PubMed Central

    Simoneau, Anne R

    2006-01-01

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

  13. Managing the low-socioeconomic-status prostate cancer patient.

    PubMed Central

    Rayford, Walter

    2006-01-01

    Management of patients with low socioeconomic status and/or low literacy who have prostate cancer presents a challenge to healthcare professionals. Improving treatment outcomes for these men requires specific educational programs to provide a better understanding of prostate cancer including careful posttreatment follow-up to ensure they have recovered well, that the cancer is not progressing and that complications are not proving troublesome. Practice nurses and health educators/navigators can play an important role in achieving these objectives. Education and knowledgeable advice can lead to earlier diagnosis of prostate cancer, improved patient participation in the treatment decision-making process and effective management of posttreatment complications. PMID:16623064

  14. Effect of n-3 and n-6 unsaturated fatty acids on prostate cancer (PC-3) and prostate epithelial (RWPE-1) cells in vitro.

    PubMed

    Meng, Hongzhou; Shen, Yuzhen; Shen, Junhui; Zhou, Feng; Shen, Shengrong; Das, Undurti N

    2013-10-29

    Prostate cancer (PCa) is one of the leading causes of death in the elderly men. Polyunsaturated fatty acids (PUFAs) regulate proliferation of cancer cells. In the present study, we evaluated the effect of various PUFAs on the proliferation and survival of human prostate cancer (PC-3) and human prostate epithelial (RWPE-1) cells in vitro.LA, GLA, AA, ALA, EPA and DHA (linoleic acid, gamma-linolenic acid, arachidonic acid, alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid respectively) when tested at 50, 100, 150, and 200 μM inhibited proliferation of RWPE-1 and PC-3 cells, except that lower concentrations of LA (25 μM) and GLA (5, 10 μM) promoted proliferation. Though all fatty acids tested produced changes in the production of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), lipoxin A4 and free radical generation by RWPE-1 and PC-3 cells, there were significant differences in their ability to do so. As expected, supplementation of various n-3 and n-6 fatty acids to RWPE-1 and PC-3 cells enhanced the content of the added fatty acids and their long-chain metabolites in these cells. In contrast to previous results, we did not find any direct correlation between inhibition of cell proliferation induced by various fatty acids and free radical generation. These results suggest that polyunsaturated fatty acids suppress proliferation of normal and tumor cells by a variety of mechanisms that may partly depend on the type(s) of cell(s) being tested and the way these fatty acids are handled by the cells. Hence, it is suggested that more deeper and comprehensive studies are needed to understand the actions of fatty acids on the growth of normal and tumor cells.

  15. Observation Versus Initial Treatment for Men With Localized, Low-Risk Prostate Cancer A Cost-Effectiveness Analysis

    PubMed Central

    Hayes, Julia H.; Ollendorf, Daniel A.; Pearson, Steven D.; Barry, Michael J.; Kantoff, Philip W.; Lee, Pablo A.; McMahon, Pamela M.

    2015-01-01

    Background Observation is underused among men with localized, low-risk prostate cancer. Objective To assess the costs and benefits of observation versus initial treatment. Design Decision analysis simulating treatment or observation. Data Sources Medicare schedules, published literature. Target Population Men ages 65 and 75 years with newly diagnosed low-risk prostate cancer (prostate-specific antigen level <10 μg/L, stage ≤T2a, Gleason score ≤3+3). Time Horizon Lifetime. Perspective Societal. Intervention Treatment (brachytherapy, intensity-modulated radiation therapy, or radical prostatectomy) or observation (active surveillance [AS] or watchful waiting [WW]). Outcome Measures Quality-adjusted life expectancy, costs. Results of Base-Case Analysis Observation was more effective and less costly than initial treatment. Compared with AS, WW provided 2 additional months of quality-adjusted life expectancy (9.02 vs. 8.85 years) at a savings of $15 374 ($24 520 vs. $39 894) in men aged 65 years and 2 additional months (6.14 vs. 5.98 years) at a savings of $11 746 ($18 302 vs. $30 048) in men aged 75 years. Brachytherapy was the most effective and least expensive initial treatment. Results of Sensitivity Analysis Treatment became more effective than observation when it led to more dramatic reductions in prostate cancer death (hazard ratio, 0.47 vs. WW and 0.64 vs. AS). Active surveillance became as effective as WW in men aged 65 years when the probability of progressing to treatment on AS decreased below 63% or when the quality of life with AS versus WW was 4% higher in men aged 65 years or 1% higher in men aged 75 years. Watchful waiting remained least expensive in all analyses. Limitation Results depend on outcomes reported in the published literature, which is limited. Conclusion Among these men, observation is more effective and costs less than initial treatment, and WW is most effective and least expensive under a wide range of clinical scenarios. Primary

  16. Effects of strength training on muscle cellular outcomes in prostate cancer patients on androgen deprivation therapy.

    PubMed

    Nilsen, T S; Thorsen, L; Fosså, S D; Wiig, M; Kirkegaard, C; Skovlund, E; Benestad, H B; Raastad, T

    2016-09-01

    Androgen deprivation therapy (ADT) improves life expectancy in prostate cancer (PCa) patients, but is associated with adverse effects on muscle mass. Here, we investigated the effects of strength training during ADT on muscle fiber cross-sectional area (CSA) and regulators of muscle mass. PCa patients on ADT were randomized to 16 weeks of strength training (STG) (n = 12) or a control group (CG; n = 11). Muscle biopsies were obtained from m. vastus lateralis and analyzed by immunohistochemistry and western blot. Muscle fiber CSA increased with strength training (898 μm(2) , P = 0.04), with the only significant increase observed in type II fibers (1076 μm(2) , P = 0.03). There was a trend toward a difference in mean change between groups myonuclei number (0.33 nuclei/fiber, P = 0.06), with the only significant increase observed in type I fibers, which decreased the myonuclear domain size of type I fibers (P = 0.05). Satellite cell numbers and the content of androgen receptor and myostatin remained unchanged. Sixteen weeks of strength training during ADT increased type II fiber CSA and reduced myonuclear domain in type I fibers in PCa patients. The increased number of satellite cells normally seen following strength training was not observed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Do Environmental Factors Modify the Genetic Risk of Prostate Cancer?

    PubMed Central

    Loeb, Stacy; Peskoe, Sarah B.; Joshu, Corinne E.; Huang, Wen-Yi; Hayes, Richard B.; Carter, H. Ballentine; Isaacs, William B.; Platz, Elizabeth A.

    2015-01-01

    Background Many SNPs influence prostate cancer risk. To what extent genetic risk can be reduced by environmental factors is unknown. Methods We evaluated effect modification by environmental factors of the association between susceptibility SNPs and prostate cancer in 1,230 incident prostate cancer cases and 1,361 controls, all white and similar ages, nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Trial. Genetic risk scores were calculated as number of risk alleles for 20 validated SNPs. We estimated the association between higher genetic risk (≥ 12 SNPs) and prostate cancer within environmental factor strata and tested for interaction. Results Men with ≥12 risk alleles had 1.98, 2.04, and 1.91 times the odds of total, advanced, and nonadvanced prostate cancer, respectively. These associations were attenuated with the use of selenium supplements, aspirin, ibuprofen, and higher vegetable intake. For selenium, the attenuation was most striking for advanced prostate cancer: compared with <12 alleles and no selenium, the OR for ≥12 alleles was 2.06 [95% confidence interval (CI), 1.67–2.55] in nonusers and 0.99 (0.38–2.58) in users (Pinteraction = 0.031). Aspirin had the most marked attenuation for nonadvanced prostate cancer: compared with <12 alleles and nonusers, the OR for ≥12 alleles was 2.25 (1.69–3.00) in nonusers and 1.70 (1.25–2.32) in users (Pinteraction = 0.009). This pattern was similar for ibuprofen (Pinteraction = 0.023) and vegetables (Pinteraction = 0.010). Conclusions This study suggests that selenium supplements may reduce genetic risk of advanced prostate cancer, whereas aspirin, ibuprofen, and vegetables may reduce genetic risk of nonadvanced prostate cancer. PMID:25342390

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

    DTIC Science & Technology

    2005-01-01

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

  19. 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.

  20. 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

  1. Imaging for Prostate Cancer Recurrence.

    PubMed

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

    2016-06-01

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

  2. Effects of sextant transrectal prostate biopsy plus additional far lateral cores in improving cancer detection rates in men with large prostate glands.

    PubMed

    Kobayashi, Takashi; Nishizawa, Koji; Watanabe, Jun; Ogura, Keiji; Mitsumori, Kenji; Ide, Yoshihiro

    2004-06-01

    To determine whether additional, far lateral cores improve the diagnostic performance of transrectal sextant biopsy in men with large prostate glands. Men with prostate volumes of 50 mL or greater in transrectal ultrasonography who were suspected of prostatic adenocarcinoma were prospectively enrolled. Biopsy criteria were defined as 2.0 ng/mL or greater of serum total prostate-specific antigen and/or abnormal findings on digital rectal examination. Four cores of far lateral biopsies were added to the standard sextant technique. Of 104 patients enrolled in the present study and undergoing biopsy, 14 (13.5%) were diagnosed as having prostate cancer and 27 (26.0%) were diagnosed as having prostatic intraepithelial neoplasia (PIN) or an atypical gland. There were no cases where cancer was only detected in the additional cores, whereas PIN/atypical gland was uniquely detected from the additional, far lateral sites in eight of the 27 patients who were diagnosed with this condition. Although the number of patients diagnosed as having PIN/atypical gland might increase with the addition of far lateral cores, this additional sampling does not improve cancer detection rates in men with large prostate glands.

  3. 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

  4. 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

  5. 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.

  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. Copyright © 2016. Published by Elsevier SAS.

  7. Antivascular Effects of Neoadjuvant Androgen Deprivation for Prostate Cancer: An In Vivo Human Study Using Susceptibility and Relaxivity Dynamic MRI

    SciTech Connect

    Alonzi, Roberto; Padhani, Anwar R.; Taylor, N. Jane; Collins, David J.; D'Arcy, James A.; Stirling, J. James; Saunders, Michele I.; Hoskin, Peter J.

    2011-07-01

    Purpose: The antivascular effects of androgen deprivation have been investigated in animal models; however, there has been minimal investigation in human prostate cancer. This study tested the hypothesis that androgen deprivation causes significant reductions in human prostate tumor blood flow and the induction of hypoxia at a magnitude and in a time scale relevant to the neoadjuvant setting before radiotherapy. Methods and Materials: Twenty patients were examined, each with five multi-parameter magnetic resonance imaging scans: two scans before the commencement of androgen suppression, one scan after 1 month of hormone treatment, and two further scans after 3 months of therapy. Quantitative parametric maps of the prostate informing on relative blood flow (rBF), relative blood volume (rBV), vascular permeability (transfer constant [K{sup trans}]), leakage space (v{sub e}) and blood oxygenation (intrinsic relaxivity [R{sub 2}*]) were calculated. Results: Tumor blood volume and blood flow decreased by 83% and 79%, respectively, in the first month (p < 0.0001), with 74% of patients showing significant changes. The proportion of individual patients who achieved significant changes in T1 kinetic parameter values after 3 months of androgen deprivation for tumor measurements was 68% for K{sup trans} and 53% for v{sub e} By 3 months, significant increases in R{sub 2}* had occurred in prostate tumor, with a rise of 41.1% (p < 0.0001). Conclusions: Androgen deprivation induces profound vascular collapse within 1 month of starting treatment. Increased R{sub 2}* in regions of prostate cancer and a decrease in blood volume suggest a reduction in tumor oxygenation.

  8. Effect of 25-Hydroxyvitamin D Status on Serological Response to Influenza Vaccine in Prostate Cancer Patients

    PubMed Central

    Chadha, Manpreet K.; Fakih, Marwan; Muindi, Josephia; Tian, Lili; Mashtare, Terry; Johnson, Candace S.; Trump, Donald

    2015-01-01

    BACKGROUND Epidemiologic data suggest that there is an association between vitamin D deficiency and influenza infection. We conducted a prospective influenza vaccination study to determine the influence of vitamin D status on serological response to influenza vaccine in prostate cancer (CaP) patients. METHODS During the 2006–2007 influenza season, CaP patients treated at Roswell Park Cancer Institute were offered vaccination with the trivalent influenza vaccine (Fluzone®, 2006–2007) and sera collected for hemagglutination inhibition (HI) assay titers before and 3 months after vaccination. Response to vaccination was defined as ≥1:40 titer ratio or a fourfold increase in titer at 3 months, against any of the three strains. Serum 25-hydroxyvitamin D (25-D3) levels were measured using DiaSorin 125I radioimmunoassay kits. RESULTS Thirty-five patients with CaP participated in the study. Median baseline 25-D3 level was 44.88 ng/ml (range: 9.16–71.98 ng/ml) Serological response against any of the three strains was noted in 80%. There was a significant effect of baseline 25-D3 level when tested as a continuous variable in relation to serological response (P = 0.0446). All patients in the upper quartile of 25-D3 level responded by mounting a serological response (P = 0.0344). None of the other baseline variables (age, race, chemotherapy status, or white cell count) had an effect on serological response. CONCLUSIONS In this study in CaP patients, a replete vitamin D status was associated with more frequent serological response to influenza vaccine. PMID:20812224

  9. Localized volume effects for late rectal and anal toxicity after radiotherapy for prostate cancer

    SciTech Connect

    Peeters, Stephanie T.H.; Lebesque, Joos V. . E-mail: j.lebesque@nki.nl; Heemsbergen, Wilma D.; Putten, Wim L.J. van; Slot, Annerie; Dielwart, Michel F.H.; Koper, Peter C.M.

    2006-03-15

    Purpose: To identify dosimetric parameters derived from anorectal, rectal, and anal wall dose distributions that correlate with different late gastrointestinal (GI) complications after three-dimensional conformal radiotherapy for prostate cancer. Methods and Materials: In this analysis, 641 patients from a randomized trial (68 Gy vs. 78 Gy) were included. Toxicity was scored with adapted Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer (RTOG/EORTC) criteria and five specific complications. The variables derived from dose-volume histogram of anorectal, rectal, and anal wall were as follows: % receiving {>=}5-70 Gy (V5-V70), maximum dose (D{sub max}), and mean dose (D{sub mean}). The anus was defined as the most caudal 3 cm of the anorectum. Statistics were done with multivariate Cox regression models. Median follow-up was 44 months. Results: Anal dosimetric variables were associated with RTOG/EORTC Grade {>=}2 (V5-V40, D{sub mean}) and incontinence (V5-V70, D{sub mean}). Bleeding correlated most strongly with anorectal V55-V65, and stool frequency with anorectal V40 and D{sub mean}. Use of steroids was weakly related to anal variables. No volume effect was seen for RTOG/EORTC Grade {>=}3 and pain/cramps/tenesmus. Conclusion: Different volume effects were found for various late GI complications. Therefore, to evaluate the risk of late GI toxicity, not only intermediate and high doses to the anorectal wall volume should be taken into account, but also the dose to the anal wall.

  10. Prostate-related antigen-derived new peptides having the capacity of inducing prostate cancer-reactive CTLs in HLA-A2+ prostate cancer patients.

    PubMed

    Harada, Mamoru; Matsueda, Satoko; Yao, Akihisa; Ogata, Rika; Noguchi, Masanori; Itoh, Kyogo

    2004-09-01

    Prostate-related antigens, including prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP), can be targets in specific immunotherapy for prostate cancer. In this study, we attempted to newly identify epitope peptides from these 2 antigens, which are immunogenic in human histocompatibility leukocyte antigen (HLA)-A2+ prostate cancer patients. Twenty-nine peptides (PSMA with 15 and PAP with 14) were prepared based on the HLA-A2 binding motif. Based on our previous finding that antigenic peptides recognized by both cellular and humoral immune systems are useful for peptide-based immunotherapy, peptide candidates were screened first by their ability to be recognized by immunoglobulin G (IgG), and then by their ability to induce peptide-specific cytotoxic T lymphocytes (CTLs). As a result, PSMA441-450 and PAP112-120 peptides were found to be frequently recognized by IgG in plasma from prostate cancer patients. These 2 candidates effectively induced HLA-A2-restricted and prostate cancer-reactive CTLs in HLA-A2+ prostate cancer patients with several HLA-A2 subtypes. In addition, their cytotoxicity was mainly dependent on peptide-specific and CD8+ T cells. These results indicate that these PSMA441-450 and PAP112-120 peptides could be promising candidates for peptide-based immunotherapy for HLA-A2(+) prostate cancer.

  11. Design of Curcumin loaded Cellulose Nanoparticles for Prostate Cancer

    PubMed Central

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

    2013-01-01

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

  12. Effect of melamine on [Ca(2+)]i and viability in PC3 human prostate cancer cells.

    PubMed

    Yu, Chia-Cheng; Chou, Chiang-Ting; Sun, Te-Kung; Liang, Wei-Zhe; Cheng, Jin-Shiung; Chang, Hong-Tai; Wang, Jue-Long; Tseng, Hui-Wen; Kuo, Chun-Chi; Chen, Fu-An; Kuo, Daih-Huang; Shieh, Pochuen; Jan, Chung-Ren

    2014-11-01

    Melamine is thought to be an endocrine disrupter that affects physiology in cells. This study examined the effect of melamine on cytosolic free Ca(2+) concentrations ([Ca(2+)]i) and viability in PC3 human prostate cancer cells. Melamine evoked [Ca(2+)]i rises concentration-dependently. Melamine-evoked Ca(2+) entry was inhibited by nifedipine, econazole, SKF96365, GF109203X and phorbol 12-myristate 13 acetate. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin inhibited melamine-evoked [Ca(2+)]i rise. Conversely, treatment with melamine abolished thapsigargin-evoked [Ca(2+)]i rise. Inhibition of phospholipase C with U73122 did not alter melamine-evoked [Ca(2+)]i rise. Melamine at 500-800μM decreased cell viability, which was not reversed by pretreatment with the Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Collectively, our data suggest that in PC3 cells, melamine induced [Ca(2+)]i rises by evoking phospholipase C-independent Ca(2+) release from the endoplasmic reticulum, and Ca(2+) entry via protein kinase C-regulated store-operated Ca(2+) entry. Melamine also caused Ca(2+)-independent cell death. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. In vitro and in vivo effects of a recombinant anti-PSMA immunotoxin in combination with docetaxel against prostate cancer

    PubMed Central

    Michalska, Marta; Schultze-Seemann, Susanne; Bogatyreva, Lioudmila; Hauschke, Dieter; Wetterauer, Ulrich; Wolf, Philipp

    2016-01-01

    Docetaxel (DOC) is used for the first-line treatment of castration resistant prostate cancer (CPRC). However, the therapeutic effects are limited, only about one half of patients respond to the therapy and severe side effects possibly lead to discontinuation of treatment. Therefore, actual research is focused on the development of new DOC-based combination treatments. In this study we investigated the antitumor effects of a recombinant immunotoxin targeting the prostate specific membrane antigen (PSMA) in combination with DOC in vitro and in vivo. The immunotoxin consists of an anti-PSMA single chain antibody fragment (scFv) as binding and a truncated form of Pseudomonas aeruginosa Exotoxin A (PE40) as toxin domain. The immunotoxin induced apoptosis and specifically reduced the viability of androgen-dependent LNCaP and androgen-independent C4-2 prostate cancer cells. A synergistic cytotoxic activity was observed in combination with DOC with IC50 values in the low picomolar or even femtomolar range. Moreover, combination treatment resulted in an enhanced antitumor activity in a C4-2 SCID mouse xenograft model. This highlights the immunotoxin as a promising therapeutic agent for a future DOC-based combination therapy of CPRC. PMID:26968813

  14. Targeting Prostate Cancer with Multifunctional Nanoparticles

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0487 TITLE: Targeting Prostate Cancer with Multifunctional Nanoparticles PRINCIPAL INVESTIGATOR: Darryl Martin...Targeting Prostate Cancer with Multifunctional Nanoparticles 5b. GRANT NUMBER W81XWH-14-1-0487 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Darryl...STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Prostate cancer cells were transfected with claudin siRNA

  15. 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.

  16. 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

  17. Targeting TMPRSS2 ERG in Prostate Cancer

    DTIC Science & Technology

    2016-09-01

    molecules in prostate cancer cells for perturbations that would modulate the ERG signature. These results will provide new insights into ERG function...prostate cancer, however, the exact role of TMPRSS2-ERG in tumorigenesis is unclear, making it difficult to design assays to target its function...essential for TMPRSS2-ERG activity in prostate cancer cells (months 1-28) 1a. Generate and titer lentiviruses expressing shRNAs targeting

  18. Molecular Imaging of Prostate Cancer: PET Radiotracers

    PubMed Central

    Jadvar, Hossein

    2012-01-01

    OBJECTIVE Recent advances in the fundamental understanding of the complex biology of prostate cancer have provided an increasing number of potential targets for imaging and treatment. The imaging evaluation of prostate cancer needs to be tailored to the various phases of this remarkably heterogeneous disease. CONCLUSION In this article, I review the current state of affairs on a range of PET radiotracers for potential use in the imaging evaluation of men with prostate cancer. PMID:22826388

  19. Both IGF1R and INSR Knockdown Exert Antitumorigenic Effects in Prostate Cancer In Vitro and In Vivo

    PubMed Central

    Ofer, Philipp; Heidegger, Isabel; Eder, Iris E.; Schöpf, Bernd; Neuwirt, Hannes; Geley, Stephan; Massoner, Petra

    2015-01-01

    The IGF network with its main receptors IGF receptor 1 (IGF1R) and insulin receptor (INSR) is of major importance for cancer initiation and progression. To date, clinical studies targeting this network were disappointing and call for thorough analysis of the IGF network in cancer models. We highlight the oncogenic effects controlled by IGF1R and INSR in prostate cancer cells and show similarities as well as differences after receptor knockdown (KD). In PC3 prostate cancer cells stably transduced with inducible short hairpin RNAs, targeting IGF1R or INSR attenuated cell growth and proliferation ultimately driving cells into apoptosis. IGF1R KD triggered rapid and strong antiproliferative and proapoptotic responses, whereas these effects were less pronounced and delayed after INSR KD. Down-regulation of the antiapoptotic proteins myeloid cell leukemia-1 and survivin was observed in both KDs, whereas IGF1R KD also attenuated expression of prosurvival proteins B cell lymphoma-2 and B cell lymphoma-xL. Receptor KD induced cell death involved autophagy in particular upon IGF1R KD; however, no difference in mitochondrial energy metabolism was observed. In a mouse xenograft model, induction of IGF1R or INSR KD after tumor establishment eradicated most of the tumors. After 20 days of receptor KD, tumor cells were found only in 1/14 IGF1R and 3/14 INSR KD tumor remnants. Collectively, our data underline the oncogenic functions of IGF1R and INSR in prostate cancer namely growth, proliferation, and survival in vitro as well as in vivo and identify myeloid cell leukemia-1 and survivin as important mediators of inhibitory and apoptotic effects. PMID:26452103

  20. Both IGF1R and INSR Knockdown Exert Antitumorigenic Effects in Prostate Cancer In Vitro and In Vivo.

    PubMed

    Ofer, Philipp; Heidegger, Isabel; Eder, Iris E; Schöpf, Bernd; Neuwirt, Hannes; Geley, Stephan; Klocker, Helmut; Massoner, Petra

    2015-12-01

    The IGF network with its main receptors IGF receptor 1 (IGF1R) and insulin receptor (INSR) is of major importance for cancer initiation and progression. To date, clinical studies targeting this network were disappointing and call for thorough analysis of the IGF network in cancer models. We highlight the oncogenic effects controlled by IGF1R and INSR in prostate cancer cells and show similarities as well as differences after receptor knockdown (KD). In PC3 prostate cancer cells stably transduced with inducible short hairpin RNAs, targeting IGF1R or INSR attenuated cell growth and proliferation ultimately driving cells into apoptosis. IGF1R KD triggered rapid and strong antiproliferative and proapoptotic responses, whereas these effects were less pronounced and delayed after INSR KD. Down-regulation of the antiapoptotic proteins myeloid cell leukemia-1 and survivin was observed in both KDs, whereas IGF1R KD also attenuated expression of prosurvival proteins B cell lymphoma-2 and B cell lymphoma-xL. Receptor KD induced cell death involved autophagy in particular upon IGF1R KD; however, no difference in mitochondrial energy metabolism was observed. In a mouse xenograft model, induction of IGF1R or INSR KD after tumor establishment eradicated most of the tumors. After 20 days of receptor KD, tumor cells were found only in 1/14 IGF1R and 3/14 INSR KD tumor remnants. Collectively, our data underline the oncogen