Science.gov

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. Genetic variation: effect on prostate cancer

    PubMed Central

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

    2014-01-01

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

  3. 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 ...

  4. Vaccine Treatment for Prostate Cancer

    MedlinePlus

    ... Preventing and treating prostate cancer spread to bones Vaccine treatment for prostate cancer Sipuleucel-T (Provenge) is ... less advanced prostate cancer. Possible side effects of vaccine treatment Side effects from the vaccine tend to ...

  5. What is Prostate Cancer?

    MedlinePlus

    ... Topic Key statistics for prostate cancer What is prostate cancer? Cancer starts when cells in the body begin ... through the center of the prostate. Types of prostate cancer Almost all prostate cancers are adenocarcinomas . These cancers ...

  6. Prostate cancer screenings

    MedlinePlus

    ... not do an accurate job of screening for prostate cancer. ... and anxiety, even if you do not have prostate cancer. Side effects from further testing. If your PSA test is higher than normal, you may need to ...

  7. Prostate cancer.

    PubMed

    Castillejos-Molina, Ricardo Alonso; Gabilondo-Navarro, Fernando Bernardo

    2016-04-01

    Prostate cancer is the most frequent tumor found in men worldwide and in Mexico in particular. Age and family history are the main risk factors. The diagnosis is made by prostate biopsy in patients with abnormalities detected in their prostate-specific antigen (PSA) levels or digital rectal exam (DRE). This article reviews screening and diagnostic methods as well as treatment options for patients diagnosed with prostate cancer. PMID:27557386

  8. Hormone therapy for prostate cancer

    MedlinePlus

    Androgen deprivation therapy; ADT; Androgen suppression therapy; Combined androgen blockade ... Androgens cause prostate cancer cells to grow. Hormone therapy for prostate cancer lowers the effect level of ...

  9. Prostate cancer

    MedlinePlus

    ... spread of the cancer. But it does not cure the cancer. If prostate cancer spreads even after hormone therapy, ... the Gleason score) when you are diagnosed. A cure is possible if the cancer has not spread. Hormone treatment can improve survival, ...

  10. 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.

  11. [Prostate cancer].

    PubMed

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

    2016-02-01

    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.

  12. [Prostate cancer].

    PubMed

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

    2016-02-01

    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. PMID:25727526

  13. Prostate Cancer

    PubMed Central

    Vickers, Andrew J.; Lilja, Hans

    2010-01-01

    Two groundbreaking trials have this year reported conflicting results as to the benefit of screening for prostate cancer. Careful interpretation in the light of contemporary data might, however, reveal the true value of this intervention. PMID:19498406

  14. 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/ ...

  15. Prostate Cancer Prevention

    MedlinePlus

    ... finasteride who did have prostate cancer had more aggressive tumors . The number of deaths from prostate cancer ... men that did not. The number of less aggressive prostate cancers was lower, but the number of ...

  16. 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 ...

  17. 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.

  18. 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. PMID:24188663

  19. 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

  20. 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

  1. Effect of erectile dysfunction following prostate cancer treatment.

    PubMed

    McConkey, Robert

    2015-11-18

    Prostate cancer is the most prevalent non-cutaneous cancer in men worldwide. As a result of increased survival rates, men and their partners are living longer with the sexual sequelae of active treatments for prostate cancer, including surgery, radiotherapy and hormone therapy. The effect of erectile dysfunction on the patient and his partner is complex; many men experience psychosocial effects influenced by their hegemonic masculine beliefs. Some men experience difficulties in addressing their needs and require support while they attempt to reframe their beliefs about masculinity. The PLISSIT model can be used to guide healthcare practitioners in assessing and addressing the needs of this group of patients. The man's partner should be included in assessment and interventions where appropriate. PMID:26576913

  2. 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 ...

  3. Chemoprevention of prostate cancer.

    PubMed

    Stephenson, Andrew J; Abouassaly, Robert; Klein, Eric A

    2010-02-01

    Prostate cancer is an appropriate target for primary chemoprevention because of its ubiquity, disease-related mortality, treatment-related morbidity, and long latency period. The PCPT and REDUCE trials demonstrate that this cancer can be prevented by a relatively nontoxic oral pharmacologic agent (5alpha-reductase inhibitors). Evidence from the SELECT trial argues against the recommendation of the use of vitamins and micronutrients as chemoprevention of prostate cancer. Dietary modification may substantially alter a man's risk of prostate cancer, but the specific dietary manipulations that are necessary are poorly defined and these may need to be instituted in early adulthood to be successful. 5alpha-reductase inhibitors represent an effective primary prevention strategy, and these agents should be used more liberally for the prevention of prostate cancer, particularly in high-risk patients. PMID:20152515

  4. Prostate cancer markers: An update

    PubMed Central

    PENTYALA, SRINIVAS; WHYARD, TERRY; PENTYALA, SAHANA; MULLER, JOHN; PFAIL, JOHN; PARMAR, SUNJIT; HELGUERO, CARLOS G.; KHAN, SARDAR

    2016-01-01

    As the most common noncutaneous malignancy in American men, prostate cancer currently accounts for 29% of all diagnosed cancers, and ranks second as the cause of cancer fatality in American men. Prostatic cancer is rarely symptomatic early in its course and therefore disease presentation often implies local extension or even metastatic disease. Thus, it is extremely critical to detect and diagnose prostate cancer in its earliest stages, often prior to the presentation of symptoms. Three of the most common techniques used to detect prostate cancer are the digital rectal exam, the transrectal ultrasound, and the use of biomarkers. This review presents an update regarding the field of prostate cancer biomarkers and comments on future biomarkers. Although there is not a lack of research in the field of prostate cancer biomarkers, the discovery of a novel biomarker that may have the advantage of being more specific and effective warrants future scientific inquiry. PMID:26998261

  5. Effects of metal ions, catechins, and their interactions on prostate cancer.

    PubMed

    Yu, Hai-Ning; Shen, Sheng-Rong; Yin, Jun-Jie

    2007-01-01

    Prostate cancer is threatening human health heavily, for its causes are related to diet, genetic factors, and lifestyle. Metal ions, which are necessary to our health, are important factors inducing many diseases including prostate cancer in the condition of absence or excess. Epidemiological and laboratory studies provide convincing evidence that green tea prevents and cures prostate cancer. Practically, interactions of catechins, which are the main bioactive components in green tea or GTP, with metal ions have a new aspect to investigate their mechanism in preventing and curing prostate cancer. In the present paper, we summarize some research about the effects of catechins with metal ions related to prostate cancer and their interactions on prostate cancer. PMID:17987445

  6. Prostate Cancer Support Groups

    PubMed Central

    Chambers, Suzanne; Garrett, Bernie; Bottorff, Joan L.; McKenzie, Michael; Han, Christina S.; Ogrodniczuk, John S.

    2015-01-01

    To understand prostate cancer (PCa) specialists’ views about prostate cancer support groups (PCSGs), a volunteer sample of Canada-based PCa specialists (n = 150), including urologists (n = 100), radiation oncologists (n = 40), and medical oncologists (n = 10) were surveyed. The 56-item questionnaire used in this study included six sets of attitudinal items to measure prostate cancer specialists’ beliefs about positive and negative influences of PCSGs, reasons for attending PCSGs, the attributes of effective PCSGs, and the value of face-to-face and web-based PCSGs. In addition, an open-ended question was included to invite additional input from participants. Results showed that PCSGs were positively valued, particularly for information sharing, education and psychosocial support. Inclusivity, privacy, and accessibility were identified as potential barriers, and recommendations were made for better marketing PCSGs to increase engagement. Findings suggest prostate cancer specialists highly valued the role and potential benefits of face-to-face PCSGs. Information provision and an educational role were perceived as key benefits. Some concerns were expressed about the ability of web-based PCSGs to effectively engage and educate men who experience prostate cancer. PMID:25061087

  7. 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.

  8. Screening for Prostate Cancer

    MedlinePlus

    ... of Internal Medicine Summaries for Patients Screening for Prostate Cancer: A Guidance Statement From the Clinical Guidelines Committee ... Physicians The full report is titled “Screening for Prostate Cancer: A Guidance Statement From the Clinical Guidelines Committee ...

  9. Prostate Cancer Screening

    MedlinePlus

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

  10. Chemopreventive Effect of PSP Through Targeting of Prostate Cancer Stem Cell-Like Population

    PubMed Central

    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. PMID:21603625

  11. Synergistic Effects of Dietary Natural Products as Anti-Prostate Cancer Agents.

    PubMed

    Vue, Bao; Zhang, Sheng; Chen, Qiao-Hong

    2015-12-01

    This review is to describe synergistic effects of various combinations of dietary natural products including curcumin, quercetin, soybean isoflavones, silibinin, and EGCG that have potential for the treatment of prostate cancer. These data can provide valuable insights into the future rational design and development of synergistic and/or hybrid agents for potential treatment of prostate cancer. PMID:26882694

  12. PDEF in prostate cancer.

    PubMed

    Sood, Ashwani K; Kim, Hyung; Geradts, Joseph

    2012-05-01

    Prostate-derived Ets factor (PDEF) is a relatively recently described member of the Ets family of transcription factors. It differs from other family members in its restricted and epithelial-specific expression in normal tissues and its unique DNA-binding motif that together may impart interesting specificity to its function. This communication reviews our current understanding of the expression characteristics of PDEF in normal prostate and in prostate cancer. Also, the biochemical and genetic evidence relating to the role of this transcription factor in prostate cancer is reviewed. Most evidence is consistent with an oncogenic role for PDEF in prostate cancer. Specific observations about the loss of PDEF expression in prostate tumors and its apparent role as a prostate tumor suppressor are also discussed. PDEF is one of the few transcription factors with potential to have a significant impact on the management of prostate cancer. A better understanding of its biology and its role in prostate cancer is urgently needed.

  13. 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

  14. Effects of Serum Triglycerides on Prostate Cancer and Breast Cancer Risk: A Meta-Analysis of Prospective Studies.

    PubMed

    Ma, Hong-Qun; Cui, Lian-Hua; Li, Cheng-Cheng; Yu, Zhuang; Piao, Jin-Mei

    2016-10-01

    Epidemiological studies show conflicting results regarding the link between serum triglyceride and the risk of prostate cancer and breast cancer. Therefore, we performed a meta-analysis of prospective studies to clarify this association. We searched PubMed, EMBASE, the Chinese Biomedical Database (CBM), and the China National Knowledge Infrastructure (CNKI) database to identify relevant prospective studies of the relationship between serum triglyceride and prostate cancer and breast cancer risk. Study-specific estimates adjusting for potential confounders were combined to evaluate a summary relative risks (RRs) and 95% confidence intervals (95% CIs) using a fixed- or random-effects model. A total of 11 prospective studies (619,410 subjects and 15,691 incident prostate cancer patients) and 8 prospective studies (590,878 subjects and 12,177 incident breast cancer patients) were respectively included in our meta-analysis to assess the associations of serum triglyceride with prostate cancer and breast cancer risk. The pooled adjusted RR estimates for prostate cancer and breast cancer for the highest versus the lowest exposure levels of serum triglycerides were 0.95 (95% CI: 0.87-1.04) and 0.94 (95% CI: 0.87-1.00), respectively. Additionally, a dose-response analysis revealed that serum levels of triglycerides were not associated with the risk of prostate cancer and breast cancer. We found that serum triglyceride was not related to the risk of prostate cancer and breast cancer. PMID:27618148

  15. [Chemotherapy for prostate cancer].

    PubMed

    Rauchenwald, Michael; De Santis, Maria; Fink, Eleonore; Höltl, Wolfgang; Kramer, Gero; Marei, Isabella-Carolina; Neumann, Hans-Jörg; Reissigl, Andreas; Schmeller, Nikolaus; Stackl, Walter; Hobisch, Alfred; Krainer, Michael

    2008-01-01

    For many years the benefit of chemotherapy in patients with prostate cancer was thought to be limited to palliation of late-stage disease, and thus this treatment option only became involved in patient care towards the end of the disease process, if at all. However, two landmark phase-III trials with docetaxel-based therapy (TAX 327 and Southwest Oncology Group, SWOG, 9916) have shown a survival benefit for patients with hormone refractory prostate cancer (HRPC) thus prompting a change in patterns of care. With raising interest for chemotherapeutic options and clinical trials for new drugs and new indications (neoadjuvant therapy, adjuvant therapy, increasing PSA levels after local treatment, and hormone sensitive cancer) under way our goal was to review within the context of a multidisciplinary team the available evidence and explore the standard for the medical treatment of prostate cancer outside of clinical trials. We are carefully evaluating the current treatment recommendations based on the available evidence and highlight potential future treatment options but also discuss important clinical topics (treatment until progression versus the advantage of chemo holidays, definition of particular patient subgroups and potential second line options) for which there are no clear cut answers to date. The role and importance of radiotherapy, biphosphonate treatment and the medical management of pain and side effects is also discussed. The multitude of treatment options for patients with advanced prostate cancer clearly asks for a close collaboration between urologists, medical oncologists and radiation therapists. PMID:18726672

  16. Biomarkers for prostate cancer.

    PubMed

    Makarov, Danil V; Loeb, Stacy; Getzenberg, Robert H; Partin, Alan W

    2009-01-01

    The development of biomarkers for prostate cancer screening, detection, and prognostication has revolutionized the management of this disease. Prostate-specific antigen (PSA) is a useful, though not specific, biomarker for detecting prostate cancer. We review the literature on prostate cancer biomarkers, including serum markers (PAP, tPSA, fPSA, proPSA, PSAD, PSAV, PSADT, EPCA, and EPCA-2), tissue markers (AMACR, methylated GSTP1, and the TMPRSS2-ETS gene rearrangement), and a urine marker (DD3PCA3/UPM-3). Future research should focus on validation of already existing biomarkers and the discovery of new markers to identify men with aggressive prostate cancer.

  17. Anti-androgenic effects of flavonols in prostate cancer

    PubMed Central

    Boam, Tristan

    2015-01-01

    Dietary-derived agents, such as the flavonoids, are of particular interest for prostate cancer (PCa) chemoprevention as they may offer a favourable safety and side-effect profile. An agent that demonstrates action on the androgen receptor (AR) axis may have value for preventing or treating castrate-resistant PCa. Four main flavonols – quercetin, myricetin, kaempferol, and fisetin – have been demonstrated in laboratory studies to have chemopreventive action in both castrate-resistant and castrate-sensitive PCa models. Mechanisms of flavonol action on the AR axis in PCa have been proposed to be inhibition of the 5α-reductase enzymes, direct androgen competition, suppression of the AR complex and transactivation by coregulators such as c-Jun, Sp1, and the PI3K/Akt pathway. It is, however, still unclear with current levels of evidence whether AR axis-mediated effects can fully account for the flavonols’ chemopreventive action. PMID:26557883

  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. 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.…

  20. Design of the North Carolina Prostate Cancer Comparative Effectiveness and Survivorship Study (NC ProCESS).

    PubMed

    Chen, Ronald C; Carpenter, William R; Kim, Mimi; Hendrix, Laura H; Agans, Robert P; Meyer, Anne-Marie; Hoffmeyer, Anna; Reeve, Bryce B; Nielsen, Matthew E; Usinger, Deborah S; Strigo, Tara S; Jackman, Anne M; Anderson, Mary; Godley, Paul A

    2015-01-01

    The North Carolina Prostate Cancer Comparative Effectiveness & Survivorship Study (NC ProCESS) was designed in collaboration with stakeholders to compare the effectiveness of different treatment options for localized prostate cancer. Using the Rapid Case Ascertainment system of the North Carolina Central Cancer Registry, 1,419 patients (57% of eligible) with newly-diagnosed localized prostate cancer were enrolled from January 2011 to June 2013, on average 5 weeks after diagnosis. All participants were enrolled prior to treatment and this population-based cohort is sociodemographically diverse. Prospective follow-up continues to collect data on treatments received, disease control, survival and patient-reported outcomes. This study highlights several important considerations regarding stakeholder involvement, study design and generalizability regarding comparative effectiveness research in prostate cancer.

  1. Predictive computational modeling to define effective treatment strategies for bone metastatic prostate cancer.

    PubMed

    Cook, Leah M; Araujo, Arturo; Pow-Sang, Julio M; Budzevich, Mikalai M; Basanta, David; Lynch, Conor C

    2016-01-01

    The ability to rapidly assess the efficacy of therapeutic strategies for incurable bone metastatic prostate cancer is an urgent need. Pre-clinical in vivo models are limited in their ability to define the temporal effects of therapies on simultaneous multicellular interactions in the cancer-bone microenvironment. Integrating biological and computational modeling approaches can overcome this limitation. Here, we generated a biologically driven discrete hybrid cellular automaton (HCA) model of bone metastatic prostate cancer to identify the optimal therapeutic window for putative targeted therapies. As proof of principle, we focused on TGFβ because of its known pleiotropic cellular effects. HCA simulations predict an optimal effect for TGFβ inhibition in a pre-metastatic setting with quantitative outputs indicating a significant impact on prostate cancer cell viability, osteoclast formation and osteoblast differentiation. In silico predictions were validated in vivo with models of bone metastatic prostate cancer (PAIII and C4-2B). Analysis of human bone metastatic prostate cancer specimens reveals heterogeneous cancer cell use of TGFβ. Patient specific information was seeded into the HCA model to predict the effect of TGFβ inhibitor treatment on disease evolution. Collectively, we demonstrate how an integrated computational/biological approach can rapidly optimize the efficacy of potential targeted therapies on bone metastatic prostate cancer. PMID:27411810

  2. Predictive computational modeling to define effective treatment strategies for bone metastatic prostate cancer

    PubMed Central

    Cook, Leah M.; Araujo, Arturo; Pow-Sang, Julio M.; Budzevich, Mikalai M.; Basanta, David; Lynch, Conor C.

    2016-01-01

    The ability to rapidly assess the efficacy of therapeutic strategies for incurable bone metastatic prostate cancer is an urgent need. Pre-clinical in vivo models are limited in their ability to define the temporal effects of therapies on simultaneous multicellular interactions in the cancer-bone microenvironment. Integrating biological and computational modeling approaches can overcome this limitation. Here, we generated a biologically driven discrete hybrid cellular automaton (HCA) model of bone metastatic prostate cancer to identify the optimal therapeutic window for putative targeted therapies. As proof of principle, we focused on TGFβ because of its known pleiotropic cellular effects. HCA simulations predict an optimal effect for TGFβ inhibition in a pre-metastatic setting with quantitative outputs indicating a significant impact on prostate cancer cell viability, osteoclast formation and osteoblast differentiation. In silico predictions were validated in vivo with models of bone metastatic prostate cancer (PAIII and C4-2B). Analysis of human bone metastatic prostate cancer specimens reveals heterogeneous cancer cell use of TGFβ. Patient specific information was seeded into the HCA model to predict the effect of TGFβ inhibitor treatment on disease evolution. Collectively, we demonstrate how an integrated computational/biological approach can rapidly optimize the efficacy of potential targeted therapies on bone metastatic prostate cancer. PMID:27411810

  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. 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.

  5. 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

  6. 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. PMID:27054343

  7. Prostate Cancer Foundation

    MedlinePlus

    ... Close About Us Our Story A Legacy of Leadership About the Prostate Cancer Foundation CEO Message Why ... Cancer Board of Directors Annual Report & Financials Our Leadership Leadership Team A Legacy of Leadership Featured Take ...

  8. Prostate cancer (image)

    MedlinePlus

    Treatment of prostate cancer varies depending on the stage of the cancer (i.e., spread) and may include surgical removal, radiation, chemotherapy, hormonal manipulation or a combination of these treatments.

  9. 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 ...

  10. What Is Prostate Cancer?

    MedlinePlus Videos and Cool Tools

    ... the more likely he is to develop the disease. Physician: Come on back, first room. Narrator: Most ... cancer. Prostate cancer is really a spectrum of diseases where on one end of the spectrum there ...

  11. Detecting Prostate Cancer

    MedlinePlus Videos and Cool Tools

    ... abnormal and raises the index of suspicion that cancer may be present. Narrator: While the use of ... examination does not mean that they have prostate cancer. It means that we're concerned about it ...

  12. Cost-effectiveness of Prostate Cancer Screening: A Simulation Study Based on ERSPC Data

    PubMed Central

    de Carvalho, T. M.; Auvinen, A.; Zappa, M.; Nelen, V.; Kwiatkowski, M.; Villers, A.; Páez, A.; Moss, S. M.; Tammela, T. L. J.; Recker, F.; Denis, L.; Carlsson, S.V.; Wever, E. M.; Bangma, C. H.; Schröder, F. H.; Roobol, M. J.; Hugosson, J.; de Koning, H. J.

    2015-01-01

    Background: The results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial showed a statistically significant 29% prostate cancer mortality reduction for the men screened in the intervention arm and a 23% negative impact on the life-years gained because of quality of life. However, alternative prostate-specific antigen (PSA) screening strategies for the population may exist, optimizing the effects on mortality reduction, quality of life, overdiagnosis, and costs. Methods: Based on data of the ERSPC trial, we predicted the numbers of prostate cancers diagnosed, prostate cancer deaths averted, life-years and quality-adjusted life-years (QALY) gained, and cost-effectiveness of 68 screening strategies starting at age 55 years, with a PSA threshold of 3, using microsimulation modeling. The screening strategies varied by age to stop screening and screening interval (one to 14 years or once in a lifetime screens), and therefore number of tests. Results: Screening at short intervals of three years or less was more cost-effective than using longer intervals. Screening at ages 55 to 59 years with two-year intervals had an incremental cost-effectiveness ratio of $73000 per QALY gained and was considered optimal. With this strategy, lifetime prostate cancer mortality reduction was predicted as 13%, and 33% of the screen-detected cancers were overdiagnosed. When better quality of life for the post-treatment period could be achieved, an older age of 65 to 72 years for ending screening was obtained. Conclusion: Prostate cancer screening can be cost-effective when it is limited to two or three screens between ages 55 to 59 years. Screening above age 63 years is less cost-effective because of loss of QALYs because of overdiagnosis. PMID:25505238

  13. The Effects of Enzalutamide Monotherapy on Multiparametric 3T MR Imaging in Prostate Cancer.

    PubMed

    Van der Roest, Rosanne Cv; van Houdt, Petra J; Heijmink, Stijn Wtpj; de Jong, Jeroen; Bergman, André M; Zwart, Wilbert; van der Heide, Uulke A; van der Poel, Henk G

    2016-07-01

    The effects of enzalutamide monotherapy on prostate tumor downsizing and multiparametric MRI are currently unknown. Here we present the first case in literature of a patient with high-grade prostate cancer who underwent 3 months of neoadjuvant enzalutamide, for which the effects on mpMRI and histology were determined. Tumor size reduction and downstaging were noted. Neoadjuvant enzalutamide resulted in an increase in ADC value on the DWI-MRI sequences. Histological changes were also observed. PMID:27335799

  14. Cancer of the Prostate

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 180,890 % of All New Cancer Cases 10.7% Estimated Deaths in 2016 26,120 % of All Cancer ... of This Cancer : In 2013, there were an estimated 2,850,139 men living with prostate cancer ...

  15. 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 ...

  16. 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

  17. Chemoprevention of prostate cancer.

    PubMed

    Rittmaster, Roger S

    2011-06-01

    Over the past two decades, many more men are diagnosed with prostate cancer then die of the disease. This increase in diagnosis has led to aggressive treatment of indolent disease in many individuals and has been the impetus for finding a means of reducing the risk of prostate cancer. In the past decade, there have been eight large trials of prostate cancer risk reduction using dietary supplements, 5α-reductase inhibitors, or anti-estrogens. The only two trials which have demonstrated efficacy are those involving 5α-reductase inhibitors: the PCPT (finasteride) and REDUCE (dutasteride). This review examines prostate cancer risk reduction, with emphasis on conclusions that can be drawn from these two landmark studies. PMID:21604953

  18. 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.

  19. 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. PMID:25960237

  20. 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

  1. 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.

  2. Prevention strategies for prostate cancer.

    PubMed

    Schmitz-Dräger, B J; Lümmen, G; Bismarck, E; Fischer, C

    2012-12-01

    Through the last decade consideration of the role of vitamins and minerals in primary prevention of genitourinary tumors has dramatically changed. Despite all efforts efficacy of a specific compound has not been proven, so far. In consequence, recommendations for a use of vitamins or other supplements with the intention of prostate cancer prevention should be avoided today. In contrast, there is some evidence that life style modification might be helpful: recent investigations suggest that smoking may be involved in prostate cancer carcinogenesis. In addition, there is evidence that moderate food consumption, reduction of dairy products and an Asian or Mediterranean diet might not only prevent prostate cancer but also harbors additional beneficial effects on general health. This move from single compounds to more complex diets can be considered as a change of paradigm in prostate cancer prevention and could be the starting point of future epidemiological research. Disappointing findings with regards to nutritional cancer prevention contrast with a solid evidence concerning the efficacy of chemoprevention using 5a-reductase inhibitors: Long-term use of Finasteride and Dutasteride significantly reduces prostate cancer detection. Further candidate drugs are under investigation. However, translation of these findings into urological practice remains a matter of controversial discussion. PMID:23288209

  3. 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.

  4. Staging of prostate cancer.

    PubMed

    Cheng, Liang; Montironi, Rodolfo; Bostwick, David G; Lopez-Beltran, Antonio; Berney, Daniel M

    2012-01-01

    Prostatic carcinoma (PCa) is a significant cause of cancer morbidity and mortality worldwide. Accurate staging is critical for prognosis assessment and treatment planning for PCa. Despite the large volume of clinical activity and research, the challenge to define the most appropriate and clinically relevant staging system remains. The pathologically complex and uncertain clinical course of prostate cancer further complicates the design of staging classification and a substaging system suitable for individualized care. This review will focus on recent progress and controversial issues related to prostate cancer staging. The 2010 revision of the American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumour, node and metastasis (TNM) system is the most widely used staging system at this time. Despite general acceptance of the system as a whole, there is controversy and uncertainty about its application, particularly for T2 subclassification. The three-tiered T2 classification system for organ-confined prostate cancer is superfluous, considering the biology and anatomy of PCa. A tumour size-based substaging system may be considered in the future TNM subclassification of pT2 cancer. Lymph node status is one of the most important prognostic factors for prostate cancer. Nevertheless, clinical outcomes in patients with positive lymph nodes are variable. Identification of patients at the greatest risk of systemic progression helps in the selection of appropriate therapy. The data suggest that the inherent aggressiveness of metastatic prostate cancer is closely linked to the tumour volume of lymph node metastasis. We recommend that a future TNM staging system should consider subclassification of node-positive cancer on the basis of nodal cancer volume, using the diameter of the largest nodal metastasis and/or the number of positive nodes.

  5. Staging of prostate cancer.

    PubMed

    Cheng, Liang; Montironi, Rodolfo; Bostwick, David G; Lopez-Beltran, Antonio; Berney, Daniel M

    2012-01-01

    Prostatic carcinoma (PCa) is a significant cause of cancer morbidity and mortality worldwide. Accurate staging is critical for prognosis assessment and treatment planning for PCa. Despite the large volume of clinical activity and research, the challenge to define the most appropriate and clinically relevant staging system remains. The pathologically complex and uncertain clinical course of prostate cancer further complicates the design of staging classification and a substaging system suitable for individualized care. This review will focus on recent progress and controversial issues related to prostate cancer staging. The 2010 revision of the American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumour, node and metastasis (TNM) system is the most widely used staging system at this time. Despite general acceptance of the system as a whole, there is controversy and uncertainty about its application, particularly for T2 subclassification. The three-tiered T2 classification system for organ-confined prostate cancer is superfluous, considering the biology and anatomy of PCa. A tumour size-based substaging system may be considered in the future TNM subclassification of pT2 cancer. Lymph node status is one of the most important prognostic factors for prostate cancer. Nevertheless, clinical outcomes in patients with positive lymph nodes are variable. Identification of patients at the greatest risk of systemic progression helps in the selection of appropriate therapy. The data suggest that the inherent aggressiveness of metastatic prostate cancer is closely linked to the tumour volume of lymph node metastasis. We recommend that a future TNM staging system should consider subclassification of node-positive cancer on the basis of nodal cancer volume, using the diameter of the largest nodal metastasis and/or the number of positive nodes. PMID:22212080

  6. Understanding Prostate Cancer: Newly Diagnosed

    MedlinePlus

    ... Wellness PCF Spotlight Glossary African American Men Understanding Prostate Cancer Newly Diagnosed Newly Diagnosed Staging the Disease Issues ... you care about has recently been diagnosed with prostate cancer, this section will help guide you through the ...

  7. 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.

  8. Prostate cancer. Foreword.

    PubMed

    Patel, Hiten R H

    2014-11-01

    Professor Hiten Patel is an expert in Laparoscopic and Robotic Surgery for treating prostate disease. He is also a leading researcher in basic science and `clinical research. His basic science research is focused on studying the pathways for improving prostate cancer diagnosis and prognosis through biomarker application, and his clinical research includes new technology applications for training surgeons and improving patient care outcome. Prof Patel is also Chairman of the Urology group for the Enhanced Recovery after Surgery Society.

  9. Effect of cyclin G2 on proliferative ability of prostate cancer PC-3 cell.

    PubMed

    Cui, D W; Cheng, Y J; Jing, S W; Sun, G G

    2014-04-01

    This study aimed to analyze the expression, clinical significance of cyclin G2 (CCNG2) in prostate carcinoma, and the biological effect in its cell line by CCNG2 overexpression. Immunohistochemistry and Western blot were used to analyze CCNG2 protein expression in 85 cases of prostate cancer and normal tissues to study the relationship between CCNG2 expression and clinical factors. CCNG2 lentiviral vector and empty vector were, respectively, transfected into prostate cancer PC-3 cell line. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the mRNA level and protein of CCNG2. MTT assay and cell cycle were also conducted as to the influence of the upregulated expression of CCNG2 that might be found on PC-3 cells biological effect. The level of CCNG2 protein expression was found to be significantly lower in prostate cancer tissue than normal tissues (P < 0.05). The level of CCNG2 protein expression was not correlated with age, PSA contention, and tumor size (P < 0.05), but it was correlated with lymph node metastasis, clinic stage, and Gleason score (P < 0.05). The result of biological function shown that PC-3 cell transfected CCNG2 had a lower survival fraction, more percentage of the G0/G1 phases, and lower CDK2 protein expression compared with PC-3 cell untransfected CCNG2 (P < 0.05). CCNG2 expression decreased in prostate cancer and correlated significantly with lymph node metastasis, clinic stage, and Gleason score, suggesting that CCNG2 may play important roles as a negative regulator to prostate cancer cell.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. Prostate cancer biomarkers: an update.

    PubMed

    Romero Otero, Javier; Garcia Gomez, Borja; Campos Juanatey, Felix; Touijer, Karim A

    2014-04-01

    Many aspects of prostate cancer diagnosis and treatment could be greatly advanced with new, effective biomarkers. Prostate-specific antigen (PSA) has multiple weaknesses as a biomarker, such as not distinguishing well between cancer and benign prostatic hyperplasia or between indolent and aggressive cancers, thus leading to overtreatment, especially unnecessary biopsies. PSA also often fails to indicate accurately which patients are responding to a given treatment. Yet PSA is the only prostate cancer biomarker routinely used by urologists. Here, we provide updated information on the most relevant of the other biomarkers currently in use or in development for prostate cancer. Recent research shows improvement over using PSA alone by comparing total PSA (tPSA) or free PSA (fPSA) with new, related markers, such as prostate cancer antigen (PCA) 3, the individual molecular forms of PSA (proPSA, benign PSA, and intact PSA), and kallikreins other than PSA. Promising results have also been seen with the use of the fusion gene TMPRSS2:ERG and with various forms of the urokinase plasminogen activation receptor. Initially, there were high hopes for early PCA, but those data were not reproducible and thus research on early PCA has been abandoned. Much work remains to be done before any of these biomarkers are fully validated and accepted. Currently, the only markers discussed in this paper with Food and Drug Administration-approved tests are PCA 3 and an isoform of proPSA, [-2]proPSA. Assays are in development for most of the other biomarkers described in this paper. While the biomarker validation process can be long and filled with obstacles, the rewards will be great-in terms of both patient care and costs to the health care system.

  15. Precursors of prostate cancer.

    PubMed

    Bostwick, David G; Cheng, Liang

    2012-01-01

    High-grade prostatic intraepithelial neoplasia (PIN) is the only accepted precursor of prostatic adenocarcinoma, according to numerous studies of animal models and man; other proposed precursors include atrophy and malignancy-associated changes (with no morphologic changes). PIN is characterized by progressive abnormalities of phenotype and genotype that are intermediate between benign prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. The only method of detection of PIN is biopsy because it does not significantly elevate serum prostate-specific antigen concentration and cannot be detected by ultrasonography. The mean incidence of PIN in biopsies is 9% (range, 4%-16%), representing about 115,000 new cases of isolated PIN diagnosed each year in the United States. The clinical importance of PIN is its high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent carcinoma, especially when multifocal or observed in association with atypical small acinar proliferation (ASAP). Carcinoma develops in most patients with PIN within 10 years. Androgen deprivation therapy and radiation therapy decrease the prevalence and extent of PIN, suggesting that these forms of treatment may play a role in prevention of subsequent cancer. Multiple clinical trials to date of men with PIN have had modest success in delaying or preventing subsequent cancer. PMID:22212075

  16. Characterizing Interfraction Variations and Their Dosimetric Effects in Prostate Cancer Radiotherapy

    SciTech Connect

    Peng Cheng; Ahunbay, Ergun; Chen Guangpei; Anderson, Savannah; Lawton, Colleen; Li, X. Allen

    2011-03-01

    Purpose: To quantitatively characterize the interfraction variations and their dosimetric effects in radiotherapy for prostate cancer. Methods and Materials: A total of 486 daily computed tomography (CT) sets acquired for 20 prostate cancer patients treated with daily CT-guided repositioning using a linear accelerator and CT-on-rail combination were analyzed. The prostate, rectum, and bladder, delineated on each daily CT data set, were compared with those from the planning CT scan. Several quantities, including Dice's coefficient and the maximal overlapping rate, were used to characterize the interfraction variations. The delivered dose was reconstructed by applying the original plan to the daily CT scan with consideration of proper repositioning. Results: The mean prostate Dice's coefficient and maximal overlapping rate after bony registration was 69.7% {+-} 13.8% (standard deviation) and 85.6% {+-} 7.8% (standard deviation), respectively. The daily delivered dose distributions were generally inferior to the planned dose distribution for target coverage and/or normal structure sparing. For example, for approximately 5% of the treatment fractions, the prostate volume receiving 100% of the prescription dose decreased dramatically (15-20%) compared with its planned value. The magnitudes of the interfraction variations and their dosimetric effects indicated that, statistically, current standard repositioning using prostate alignment might be adequate for two-thirds of the fractions, but for the rest of the fractions, better on-line correction strategies, such as on-line replanning, are needed. Conclusion: Different adaptive correction schemes for prostatic interfraction changes can be used according to the anatomic changes, as quantified by the organ displacement and deformation parameters. On-line replanning is needed for approximately one-third of the treatment fractions.

  17. Berberis libanotica Ehrenb extract shows anti-neoplastic effects on prostate cancer stem/progenitor cells.

    PubMed

    El-Merahbi, Rabih; Liu, Yen-Nien; Eid, Assaad; Daoud, Georges; Hosry, Leina; Monzer, Alissar; Mouhieddine, Tarek H; Hamade, Aline; Najjar, Fadia; Abou-Kheir, Wassim

    2014-01-01

    Cancer stem cells (CSCs), including those of advanced prostate cancer, are a suggested reason for tumor resistance toward conventional tumor therapy. Therefore, new therapeutic agents are urgently needed for targeting CSCs. Despite the minimal understanding of their modes of action, natural products and herbal therapies have been commonly used in the prevention and treatment of many cancers. Berberis libanotica Ehrenb (BLE) is a plant rich in alkaloids which may possess anti-cancer activity and a high potential for eliminating CSCs. We tested the effect of BLE on prostate cancer cells and our data indicated that this extract induced significant reduction in cell viability and inhibited the proliferation of human prostate cancer cell lines (DU145, PC3 and 22Rv1) in a dose- and time-dependent manner. BLE extract induced a perturbation of the cell cycle, leading to a G0-G1 arrest. Furthermore, we noted 50% cell death, characterized by the production of high levels of reactive oxidative species (ROS). Inhibition of cellular migration and invasion was also achieved upon treatment with BLE extract, suggesting a role in inhibiting metastasis. Interestingly, BLE extract had a major effect on CSCs. Cells were grown in a 3D sphere-formation assay to enrich for a population of cancer stem/progenitor cells. Our results showed a significant reduction in sphere formation ability. Three rounds of treatment with BLE extract were sufficient to eradicate the self-renewal ability of highly resistant CSCs. In conclusion, our results suggest a high therapeutic potential of BLE extract in targeting prostate cancer and its CSCs.

  18. 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

  19. Prevention strategies in prostate cancer.

    PubMed

    Trottier, Greg; Lawrentschuk, N; Fleshner, N E

    2010-09-01

    Prostate cancer (PCa) prevention has been an exciting and controversial topic since the results of the Prostate Cancer Prevention Trial (PCPT) were published. With the recently published results of the reduce (Reduction by Dutasteride of Prostate Cancer Events) trial, interest in this topic is at a peak. Primary pca prevention will be unlikely to affect mortality significantly, but the reduction in overtreatment and the effect on quality of life from the avoidance of a cancer diagnosis are important factors to consider.This review provides a comparative update on the REDUCE and PCPT trials and some clinical recommendations. Other potential primary preventive strategies with statins, selective estrogen response modulators, and nutraceutical compounds-including current evidence for these agents and their roles in clinical practice-are discussed. Many substances that have been examined in the primary prevention of pca and for which clinical data are either negative or particularly weak are not covered.The future of PCa prevention continues to expand, with several ongoing clinical trials and much interest in tertiary prostate cancer prevention. PMID:20882132

  20. [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. PMID:27393141

  1. Vitamin E and Prostate Cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  2. Living with Prostate Cancer

    MedlinePlus

    ... pork, lamb, and processed meat (such as hot dogs, sausage, and bacon); and low in high-fat ... ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects Cancer ...

  3. Primary Care of the Prostate Cancer Survivor.

    PubMed

    Noonan, Erika M; Farrell, Timothy W

    2016-05-01

    This summary of the American Cancer Society Prostate Cancer Survivorship Care Guidelines targets primary care physicians who coordinate care of prostate cancer survivors with subspecialists. Prostate cancer survivors should undergo prostate-specific antigen screening every six to 12 months and digital rectal examination annually. Surveillance of patients who choose watchful waiting for their prostate cancer should be conducted by a subspecialist. Any hematuria or rectal bleeding must be thoroughly evaluated. Prostate cancer survivors should be screened regularly for urinary incontinence and sexual dysfunction. Patients with predominant urge incontinence symptoms, which can occur after surgical and radiation treatments, may benefit from an anticholinergic agent. If there is difficulty with bladder emptying, a trial of an alpha blocker may be considered. A phosphodiesterase type 5 inhibitor can effectively treat sexual dysfunction following treatment for prostate cancer. Osteoporosis screening should occur before initiation of androgen deprivation therapy, and patients treated with androgen deprivation therapy should be monitored for anemia, metabolic syndrome, and vasomotor symptoms. Healthy lifestyle choices should be encouraged, including weight management, regular physical activity, proper nutrition, and smoking cessation. Primary care physicians should be vigilant for psychosocial distress, including depression, among prostate cancer survivors, as well as the potential impact of this distress on patients' family members and partners. PMID:27175954

  4. Piperine, a Bioactive Component of Pepper Spice Exerts Therapeutic Effects on Androgen Dependent and Androgen Independent Prostate Cancer Cells

    PubMed Central

    Dakshinamoorthy, Gajalakshmi; Bartik, Mary Margaret; Johnson, Gary Leon; Webb, Brian; Zheng, Guoxing; Chen, Aoshuang; Kalyanasundaram, Ramaswamy; Munirathinam, Gnanasekar

    2013-01-01

    Prostate cancer is the most common solid malignancy in men, with 32,000 deaths annually. Piperine, a major alkaloid constituent of black pepper, has previously been reported to have anti-cancer activity in variety of cancer cell lines. The effect of piperine against prostate cancer is not currently known. Therefore, in this study, we investigated the anti-tumor mechanisms of piperine on androgen dependent and androgen independent prostate cancer cells. Here, we show that piperine inhibited the proliferation of LNCaP, PC-3, 22RV1 and DU-145 prostate cancer cells in a dose dependent manner. Furthermore, Annexin-V staining demonstrated that piperine treatment induced apoptosis in hormone dependent prostate cancer cells (LNCaP). Using global caspase activation assay, we show that piperine-induced apoptosis resulted in caspase activation in LNCaP and PC-3 cells. Further studies revealed that piperine treatment resulted in the activation of caspase-3 and cleavage of PARP-1 proteins in LNCaP, PC-3 and DU-145 prostate cancer cells. Piperine treatment also disrupted androgen receptor (AR) expression in LNCaP prostate cancer cells. Our evaluations further show that there is a significant reduction of Prostate Specific Antigen (PSA) levels following piperine treatment in LNCaP cells. NF-kB and STAT-3 transcription factors have previously been shown to play a role in angiogenesis and invasion of prostate cancer cells. Interestingly, treatment of LNCaP, PC-3 and DU-145 prostate cancer cells with piperine resulted in reduced expression of phosphorylated STAT-3 and Nuclear factor-κB (NF-kB) transcription factors. These results correlated with the results of Boyden chamber assay, wherein piperine treatment reduced the cell migration of LNCaP and PC-3 cells. Finally, we show that piperine treatment significantly reduced the androgen dependent and androgen independent tumor growth in nude mice model xenotransplanted with prostate cancer cells. Taken together, these results support

  5. What Tests Can Detect Prostate Cancer?

    MedlinePlus

    ... prostate cancer early detection What tests can detect prostate cancer early? The tests discussed below are used to ... also found in the blood. Most men without prostate cancer have PSA levels under 4 nanograms per milliliter ( ...

  6. 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

  7. Prostate cancer is not breast cancer

    PubMed Central

    Venniyoor, Ajit

    2016-01-01

    Cancers of the prostate and breast are hormone dependent cancers. There is a tendency to equate them and apply same algorithms for treatment. It is pointed out that metastatic prostate cancer with bone-only disease is a potentially fatal condition with a much poorer prognosis than metastatic breast cancer and needs a more aggressive approach. PMID:27051149

  8. 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

  9. [Screening for prostate cancer].

    PubMed

    Koch, Klaus; Büchter, Roland; Lange, Stefan

    2013-04-01

    Prostate cancer screening has been a controversial for decades. The recently published findings of large trials have further intensified the debate. The prospect of reducing mortality from prostate cancer is measured against the risk of over-diagnosing the disease. In individual cases, the trade-off between possible benefits and harms is possible to ascertain, so general recommendations in favor of or against PSA tests for individuals cannot be made. The majority of men, however, are not well-informed on the possible advantages and drawbacks of screening. This situation urgently needs to be corrected. The PSA test is promoted to healthy men, who need to be provided with especially detailed information. If not provided with clear and unbiased information on the risks associated with the test (above all over-diagnosis and over-treatment), these men cannot be considered to be fully informed. PMID:23535548

  10. 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

  11. 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. PMID:16982463

  12. 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.

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

    ClinicalTrials.gov

    2014-11-21

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

  14. Estrogen receptors in prostate development and cancer

    PubMed Central

    Yeh, Chiuan-Ren; Da, Jun; Song, Wenbin; Fazili, Anees; Yeh, Shuyuan

    2014-01-01

    Prostate cancer (PCa) is an androgen-sensitive disease, which can be pharmacologically controlled by androgen blockade. To date, a growing body of evidence showed that estrogen and estrogen receptors (ERs) could regulate prostate development, as well as cancer initiation and progression. This review will address the expression levels and function of ERs in different stages of PCa progression. The functions of ERs in different types of prostate cells, the ligand effect, and the potential applications of selective estrogen modulators (SERMs) will also be discussed. To further dissect ERs’ roles in prostate development, cell type specific ER knockout mouse models were generated. Results collected from the prostate cell type-specific ERαKO mouse models provided new insights about the cell type specific ERα roles in prostate development prenatally and postnatally. The results of ERs’ roles in mouse PCa mode and the correlation of ERs expression and biomedical outcome will also be discussed. PMID:25374919

  15. 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

  16. Statin Use in Prostate Cancer: An Update.

    PubMed

    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

  17. Effect of vicanicin and protolichesterinic acid on human prostate cancer cells: role of Hsp70 protein.

    PubMed

    Russo, A; Caggia, S; Piovano, M; Garbarino, J; Cardile, V

    2012-01-01

    With the aim of identifying novel agents with antigrowth and pro-apoptotic activity on prostate cancer cells, in the present study, we evaluated the effect of five lichen secondary metabolites the depsides atranorin (1), diffrattaic (2) and divaricatic (3) acids, the depsidone vicanicin (4) and the protolichesterinic acid (5) on cell growth in androgen-sensitive (LNCaP) and androgen-insensitive (DU-145) human prostate cancer cells. The cell viability was measured using MTT assay. LDH release, a marker of membrane breakdown, was also measured. For the detection of apoptosis, the evaluation of DNA fragmentation (COMET assay) and caspase-3 activity assay were employed. The expression of Bcl-2, Bax, TRAIL, COX-2, NOS2 and Hsp70 proteins was detected by western blot analysis. Generation of reactive oxygen species was measured by using a fluorescent probe. It was observed that atranorin (1), diffrattaic (2) and divaricatic (3) acids showed a lower activity inhibiting the prostate cancer cells only at more high concentrations (25 and 50μM). Whereas compounds vicanicin (4) and protolichesterinic acid (5) showed a dose-response relationship in the range of 6.25-50μM concentrations in DU-145 and LNCaP cells, activating an apoptotic process. The novel finding, in the present study, is that apoptosis induced by these compounds appears to be mediated, at least in part, via the inhibition of Hsp70 expression, that may be correlated with a modulation of redox-sensitive mechanisms. The combination of vicanicin (4) and protolichesterinic acid (5) with other anti-prostate cancer therapies could be considered a promising strategy that warrants further in vivo evaluation. PMID:22063921

  18. Molecular Imaging of Prostate Cancer.

    PubMed

    Wibmer, Andreas G; 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. PMID:26587888

  19. Drug development in prostate cancer.

    PubMed

    Ripple, G H; Wilding, G

    1999-04-01

    Despite strategies aimed at early detection and treatment, prostate cancer remains a leading cause of morbidity and mortality among males. Current therapies have limited impact on the natural history of metastatic hormone-refractory prostate cancer (HRPC). With an improved understanding of tumor biology, including apoptosis, differentiation, cell cycling and signaling, and angiogenesis, many potential new targets for therapy have been unveiled. Modulation of these processes may result in cytotoxic or cytostatic effects. The evaluation of therapies based on manipulation of these targets may not be adequately addressed by current study designs and traditional parameters of efficacy. Examples of agents currently in clinical trials that illustrate some of the challenges presented to clinical investigators include monoterpenes such as perillyl alcohol (POH), vitamin D analogs, flavones such as flavopiridol, and angiogenesis inhibitors. Agents such as these are aimed at unique cellular targets and will require novel approaches to determine their clinical utility. Unfortunately, in the United States, only a small proportion of cancer patients, including prostate cancer patients, are enrolled in clinical trials. We must do better to efficiently assess promising new treatment approaches and improve outcome for our patients.

  20. Endocrine disruptors and prostate cancer risk.

    PubMed

    Prins, Gail S

    2008-09-01

    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.

  1. 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

  2. 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

  3. HUMAN PROSTATE CANCER RISK FACTORS

    EPA Science Inventory

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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. New drugs in prostate cancer.

    PubMed

    Yoo, Sangjun; Choi, Se Young; You, Dalsan; Kim, Choung-Soo

    2016-06-01

    The standard primary treatment for advanced prostate cancer has been hormonal therapy since the 1940s. However, prostate cancer inevitably progresses to castration-resistant prostate cancer (CRPC) after a median duration of 18 months of androgen deprivation therapy. In patients with CRPC, docetaxel has been regarded as the standard treatment. However, survival advantages of docetaxel over other treatments are slim, and the need for new agents persists. In recent years, novel agents, including abiraterone, enzalutamide, cabazitaxel, radium-223, and sipuleucel-T, have been approved for the treatment of CRPC, and more such agents based on diverse mechanisms are under investigation or evaluation. In this article, the authors reviewed the current literature on recent advances in medical treatment of prostate cancer, especially CRPC. In addition, the authors elaborated on novel drugs for prostate cancer currently undergoing investigation and their mechanisms. PMID:27358841

  9. Prostate cancer stem cell biology

    PubMed Central

    Yu, Chunyan; Yao, Zhi; Jiang, Yuan; Keller, Evan. T.

    2012-01-01

    The cancer stem cell (CSC) model provides insights into pathophysiology of cancers and their therapeutic response. The CSC model has been both controversial, yet provides a foundation to explore cancer biology. In this review, we provide an overview of CSC concepts, biology and potential therapeutic avenues. We then focus on prostate CSC including (1) their purported origin as either basal-derived or luminal-derived cells; (2) markers used for prostate CSC identification; (3) alterations of signaling pathways in prostate CSCs (4) involvement of prostate CSCs in metastasis of PCa and (5) microRNA-mediated regulation of prostate CSCs. Although definitive evidence for the identification and characterization of prostate CSCs still remains unclear, future directions pursuing therapeutic targets of CSCs may provide novel insights for the treatment of PCa. PMID:22402315

  10. Mechanisms of Androgen-Independent Prostate Cancer

    PubMed Central

    Saraon, Punit; Drabovich, Andrei P.; Jarvi, Keith A.; Diamandis, Eleftherios P.

    2014-01-01

    Abstract Prostate cancer is the second leading cause of cancer-related deaths among men in North America. Almost all prostate cancers begin in an androgen-dependent state, so androgen deprivation therapy is administered and results in improved clinical outcomes. However, over time, some cancerous cells are able to survive and grow during this treatment, resulting in androgen-independent prostate cancer. At this point, the disease is fatal, as there are no effective targeted therapies available. Most prostate cancer tumors require androgen receptor (AR) signalling for survival. During the progression to androgen-independence, this signalling cascade has been found to be altered at many levels within prostate cancers. Mechanisms that enhance AR signalling during androgen deprivation include: AR gene amplifications, AR gene mutations, changes in expression of AR co-regulatory proteins, changes in expression of steroid-generating enzymes, ligand-independent activation of AR via ‘outlaw’ pathways, and AR-independent pathways that become activated, termed ‘bypass’ pathways. One or more of these aforementioned changes can lead to prostate cancer cells to gain androgen-independent properties. Understanding the molecular alterations that occur during this process will allow for improved therapeutic strategies to target key molecules and pathways important for this progression. PMID:27683456

  11. Mechanisms of Androgen-Independent Prostate Cancer

    PubMed Central

    Saraon, Punit; Drabovich, Andrei P.; Jarvi, Keith A.; Diamandis, Eleftherios P.

    2014-01-01

    Abstract Prostate cancer is the second leading cause of cancer-related deaths among men in North America. Almost all prostate cancers begin in an androgen-dependent state, so androgen deprivation therapy is administered and results in improved clinical outcomes. However, over time, some cancerous cells are able to survive and grow during this treatment, resulting in androgen-independent prostate cancer. At this point, the disease is fatal, as there are no effective targeted therapies available. Most prostate cancer tumors require androgen receptor (AR) signalling for survival. During the progression to androgen-independence, this signalling cascade has been found to be altered at many levels within prostate cancers. Mechanisms that enhance AR signalling during androgen deprivation include: AR gene amplifications, AR gene mutations, changes in expression of AR co-regulatory proteins, changes in expression of steroid-generating enzymes, ligand-independent activation of AR via ‘outlaw’ pathways, and AR-independent pathways that become activated, termed ‘bypass’ pathways. One or more of these aforementioned changes can lead to prostate cancer cells to gain androgen-independent properties. Understanding the molecular alterations that occur during this process will allow for improved therapeutic strategies to target key molecules and pathways important for this progression.

  12. Correlations between meteorological parameters and prostate cancer

    PubMed Central

    2010-01-01

    Background There exists a north-south pattern to the distribution of prostate cancer in the U.S., with the north having higher rates than the south. The current hypothesis for the spatial pattern of this disease is low vitamin D levels in individuals living at northerly latitudes; however, this explanation only partially explains the spatial distribution in the incidence of this cancer. Using a U.S. county-level ecological study design, we provide evidence that other meteorological parameters further explain the variation in prostate cancer across the U.S. Results In general, the colder the temperature and the drier the climate in a county, the higher the incidence of prostate cancer, even after controlling for shortwave radiation, age, race, snowfall, premature mortality from heart disease, unemployment rate, and pesticide use. Further, in counties with high average annual snowfall (>75 cm/yr) the amount of land used to grow crops (a proxy for pesticide use) was positively correlated with the incidence of prostate cancer. Conclusion The trends found in this USA study suggest prostate cancer may be partially correlated with meteorological factors. The patterns observed were consistent with what we would expect given the effects of climate on the deposition, absorption, and degradation of persistent organic pollutants including pesticides. Some of these pollutants are known endocrine disruptors and have been associated with prostate cancer. PMID:20409297

  13. 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

  14. 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.

  15. 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.

  16. 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. PMID:23859763

  17. 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.

  18. 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

  19. 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.

  20. Human Prostate Cancer Hallmarks Map

    PubMed Central

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

    2016-01-01

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

  1. 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

  2. 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. PMID:27613410

  3. Effect of hypertension on bacteria composition of prostate biopsy in patients with benign prostatic hyperplasia and prostate cancer in PSA grey-zone

    PubMed Central

    NI, XIAOFENG; MENG, HONGZHOU; ZHOU, FENG; YU, HAINING; XIANG, JIANJIAN; SHEN, SHENGRONG

    2016-01-01

    Diagnostic prostate cancer (PC) is difficult to diagnose by prostate biopsy, even in patients with markedly elevated PSA levels. Therefore, we aimed to identify a new, better technique to detect PC in a more consistent manner. A variety of steps were employed to validate this proposed method, including DNA extraction, polymerase chain reaction (PCR) amplification, denaturing gradient gel electrophoresis (DGGE) and DGGE band sequencing. Four transperineal prostate biopsy specimens were obtained from male patients. The patients were under the age of 65 and PSA levels were 4–10 ng/ml. We also investigated the bacteria composition of transperineal prostate biopsy in patients with benign prostatic hyperplasia (BPH) and PC by PCR-DGGE profiling. Sequences from selected bands 2 and 4 both matched with Sphingomonas, which is present in lower amounts in PC without hypertension as compared to PC with hypertension, while there were no particular differences in the BPH group. Specific bacteria from the prostate biopsy tissues provide further confidence in PC diagnosis based on a PCR approach as a diagnostic tool, while hypertension was found to be a disturbing factor that can affect the diagnosis of BPH and PC in grey-zone. PMID:27284421

  4. Safety and chemopreventive effect of Polyphenon E in preventing early and metastatic progression of prostate cancer in TRAMP mice.

    PubMed

    Kim, Seung Joon; Amankwah, Ernest; Connors, Shahnjayla; Park, Hyun Y; Rincon, Maria; Cornnell, Heather; Chornokur, Ganna; Hashim, Arig Ibrahim; Choi, Junsung; Tsai, Ya-Yu; Engelman, Robert W; Kumar, Nagi; Park, Jong Y

    2014-04-01

    Prostate cancer treatment is often accompanied by untoward side effects. Therefore, chemoprevention to reduce the risk and inhibit the progression of prostate cancer may be an effective approach to reducing disease burden. We investigated the safety and efficacy of Polyphenon E, a green tea extract, in reducing the progression of prostate cancer in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. A total of 119 male TRAMP and 119 C57BL/6J mice were treated orally with one of 3 doses of Polyphenon E (200, 500, and 1,000 mg/kg/day) in drinking water ad libitum replicating human achievable doses. Baseline assessments were performed before treatments. Safety and efficacy assessments during treatments were performed when mice were 12, 22, and 32 weeks old. The number and size of tumors in treated TRAMP mice were significantly decreased compared with untreated animals. In untreated 32 weeks old TRAMP mice, prostate carcinoma metastasis to distant sites was observed in 100% of mice (8/8), compared with 13% of mice (2/16) treated with high-dose Polyphenon E during the same period. Furthermore, Polyphenon E treatment significantly inhibited metastasis in TRAMP mice in a dose-dependent manner (P = 0.0003). Long-term (32 weeks) treatment with Polyphenon E was safe and well tolerated with no evidence of toxicity in C57BL/6J mice. Polyphenon E is an effective chemopreventive agent in preventing the progression of prostate cancer to metastasis in TRAMP mice. Polyphenon E showed no toxicity in these mouse models. Our findings provide additional evidence for the safety and chemopreventive effect of Polyphenon E in preventing metastatic progression of prostate cancer.

  5. Antagonistic effects of sodium butyrate and N-(4-hydroxyphenyl)-retinamide on prostate cancer.

    PubMed

    Kuefer, Rainer; Genze, Felicitas; Zugmaier, Waltraud; Hautmann, Richard E; Rinnab, Ludwig; Gschwend, Juergen E; Angelmeier, Marina; Estrada, Aidee; Buechele, Berthold

    2007-03-01

    Butyrates and retinoids are promising antineoplastic agents. Here we analyzed effects of sodium butyrate and N-(4-hydroxyphenyl)-retinamide (4-HPR) on prostate cancer cells as monotherapy or in combination in vitro and in vivo. Sodium butyrate and 4-HPR induced concentration-dependent growth inhibition in prostate cancer cells in vitro. The isobologram analysis revealed that sodium butyrate and 4-HPR administered together antagonize effects of each other. For the in vivo studies, a water-soluble complex (4-HPR with a cyclodextrin) was created. A single dose of sodium butyrate and 4-HPR showed a peak level in chicken plasma within 30 minutes. Both compounds induced inhibition of proliferation and apoptosis in xenografts of the chicken chorioallantoic membrane. Analysis of the cytotoxic effects of the drugs used in combination demonstrated an antagonistic effect on inhibition of proliferation and on induction of apoptosis. Prolonged jun N-terminal kinase phosphorylation induced by sodium butyrate and 4-HPR was strongly attenuated when both compounds were used in combination. Both compounds induced inhibition of NF-kappaB. This effect was strongly antagonized in LNCaP cells when the compounds were used in combination. These results indicate that combinational therapies have to be carefully investigated due to potential antagonistic effects in the clinical setting despite promising results of a monotherapy.

  6. 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

  7. Tumoristatic effects of endostatin in prostate cancer is dependent on androgen receptor status

    PubMed Central

    Isayeva, Tatyana; Moore, Lakisha D.; Chanda, Diptiman; Chen, Dongquan; Ponnazhagan, Selvarangan

    2016-01-01

    Background Although antiangiogenic therapy is a promising new line of therapy for prostate cancer, we recently reported that stable expression of endostatin arrested the progression of prostate cancer to poorly differentiated state and distant metastasis in TRAMP mice. However, the same therapy failed to provide any benefit when given either during or after the onset of metastatic switch. The present study determined the possible mechanisms behind the selective advantage of endostatin therapy in early stage disease. Methods Angiogenesis-related gene expression analysis was performed to identify target genes and molecular pathways involved in the therapy effects. Based on the results from in vivo studies, and recapitulation of the in vivo data in vitro using tumorigenic and non-tumorigenic human prostate cancer cells that are either androgen-sensitive or androgen-independent, analyses of possible mechanisms of the selective advantage of early treatment were performed using assays for cell proliferation, apoptosis, migration and cell signaling. The identified mechanisms were further confirmed in vivo. Results Results indicated that cells with high androgen receptor (AR) expression were more sensitive to endostatin treatment than androgen-independent cells with low or no AR expression. Endostatin was found to significantly downregulate the expression of growth factors, receptor tyrosine kinases, proteases, and AR both in vitro and in vivo only when the cells express high levels of AR. Cell proliferation was not influenced by endostatin treatment but migration was significantly affected only in androgen-sensitive cells. Targeted downregulation of AR prior to endostatin treatment in androgen sensitive cells and overexpression of AR in androgen independent cells indicated that the effect of endostatin via AR downregulation is mediated by a non-genotropic mechanism on Ras and RhoA pathways, and independently of AR on MAPK/ERK pathway. Conclusions These data indicate that

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

    PubMed

    Küllenberg de Gaudry, Daniela; Taylor, Lenka A; Kluth, Jessica; Hübschle, Tobias; Fritzsche, Jonas; Hildenbrand, Bernd; Pletschen, Lars; Schilli, Karin; Hodina, Arwen; Griffith, Lee S; Breul, Jürgen; Unger, Clemens; Massing, Ulrich

    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

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

    PubMed

    Küllenberg de Gaudry, Daniela; Taylor, Lenka A; Kluth, Jessica; Hübschle, Tobias; Fritzsche, Jonas; Hildenbrand, Bernd; Pletschen, Lars; Schilli, Karin; Hodina, Arwen; Griffith, Lee S; Breul, Jürgen; Unger, Clemens; Massing, Ulrich

    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.

  10. 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

  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. The Effects of Serum from Prostate Cancer Patients with Elevated Body Mass Index on Prostate Cancer Cells In Vitro

    PubMed Central

    Mora, Benjamin C; Fleshner, Neil E; Klotz, Laurence H; Venkateswaran, Vasundara

    2015-01-01

    We examined whether serum from obese, compared to non-obese, PCa (prostate cancer) patients creates a growth-enhancing tumor micro-environment in vitro. Serum from 80 subjects was divided into four groups: normal weight men with and without PCa and overweight/obese men with and without PCa. Cell proliferation, migration, and invasion were measured in LNCaP, and PC3 cells treated with patient serum were obtained from the above groups. The results reveal that proliferation of LNCaP cells was significantly (P = 0.05) greater with serum from non-obese (mean = 1.26 ± 0.20) compared to that from obese patients (mean = 1.16 ± 0.19). Serum from obese PCa patients compared to non-obese PCa patients induced significantly greater amounts of cell migration (P < 0.01) in PC3 cells. Serum from obese patients induced significantly (P < 0.01) lower amounts of cell invasion (mean = 8.2 ± 4.5) compared to non-obese patients (mean = 18.1 ± 5.0) when treated on PC3 cells. Serum TNF-α (tumor necrosis factor alpha) levels correlated with LNCaP cell proliferation in vitro in non-obese PCa (P < 0.01) and non-obese control groups (P = 0.05). All statistical calculations controlled for age, since the PCa patient groups were significantly older than the control groups (P < 0.01). In conclusion, serum from obese PCa patients induced greater PCa cell migration and lower cell proliferation and invasion in vitro. PMID:25987846

  13. The effect of superoxide anion and hydrogen peroxide imbalance on prostate cancer: an integrative in vivo and in vitro analysis.

    PubMed

    Berto, Maiquidieli Dal; Bica, Claudia Giuliano; de Sá, Gustavo Pereira; Barbisan, Fernanda; Azzolin, Verônica Farina; Rogalski, Felipe; Duarte, Marta Maria Medeiros Frescura; da Cruz, Ivana Beatrice Mânica

    2015-11-01

    The epidemiological impact of SOD2 imbalance on prostate cancer (PC) risk associated with genetic variations has previously been studied. However, we found no previous studies clarifying the nature of SOD2 effects on prostate cancer. Here, we performed integrated in vivo and in vitro protocols that analyzed the association between Ala16Val-SOD2 polymorphism and prostate cancer aggressiveness at the time of diagnosis and evaluated the effect of the imbalance on PC proliferation using the DU-145 PC cell line treated with paraquat and porphyrin. In the pharmacological model, paraquat was used to increase superoxide anion levels and porphyrin was the SOD2 analog. The results confirmed the impact of superoxide-hydrogen peroxide imbalance on PC cell biology since porphyrin decreased cell proliferation and both treatments modulated antioxidant genes. Therefore, our results corroborate previous suggestions that alteration of redox status could be exploited therapeutically in the treatment of PC. PMID:26468117

  14. Tissue ablation technologies for localized prostate cancer.

    PubMed

    Gillett, Michael D; Gettman, Matthew T; Zincke, Horst; Blute, Michael L

    2004-12-01

    Traditional treatments for men with localized prostate cancer have included both surgical removal and radiation therapy, with their potential adverse effects on patient quality of life. Thus, there has been increasing interest in the development of minimally invasive procedures that use various technologies to deliver lethal doses of heat or cold to the prostate in an attempt to kill cancer cells. At the same time, it is vital that these newer techniques ablate prostate tissue and spare vital periprostatic organs essential for maintaining function and quality of life. In this article, we evaluate the current status of tissue ablation modalities in the treatment of clinically localized prostate cancer, focusing on the different methods, early results, and possible future directions. Although still in the beginning stages, these newer forms of treatment offer exciting potential for first-line and second-line treatment of this common urologic malignancy.

  15. 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

  16. The inhibitory effects of AR/miR-190a/YB-1 negative feedback loop on prostate cancer and underlying mechanism.

    PubMed

    Xu, Shaohua; Wang, Tao; Song, Wen; Jiang, Tao; Zhang, Feng; Yin, Yu; Jiang, Shi-Wen; Wu, Kongming; Yu, Zuoren; Wang, Chenguang; Chen, Ke

    2015-08-28

    Prostate cancer at advanced stages including metastatic and castration-resistant cancer remains incurable due to the lack of effective therapies. MiR-190a belongs to the small noncoding RNA family and has an important role in breast cancer metastasis. However, it is still unknown whether miR-190a plays a role in prostate cancer development. Herein, we first observed AR/miR-190a/YB-1 forms an auto-regulatory negative feedback loop in prostate cancer: miR-190a expression was down-regulated by AR activation; YB-1 functions are as an AR activator; miR-190a inhibited AR expression and transactivation through direct binding to 3'UTR of YB-1 gene. MiR-190a contributes the human prostate cancer cell growth through AR-dependent signaling. Moreover, we examined the expression of miR-190a and observed a significant decrease in human prostate cancers. Reduced expression of miR-190a was inversely correlated to AR levels of prostate cancer patients, and patients with higher miR-190a expression in their tumor have improved tumor-free survival. Taken together, our findings identified a biochemical and functional link between miR-190a with reduced expression in advanced prostate cancer, YB-1 and AR signaling in prostate cancer.

  17. Pomegranate and its components as alternative treatment for prostate cancer.

    PubMed

    Wang, Lei; Martins-Green, Manuela

    2014-01-01

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

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

    PubMed Central

    Wang, Lei; Martins-Green, Manuela

    2014-01-01

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

  19. 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

  20. Contemporary Management of Prostate Cancer

    PubMed Central

    Cotter, Katherine; Konety, Badrinath; Ordonez, Maria A.

    2016-01-01

    Prostate cancer represents a spectrum ranging from low-grade, localized tumors to devastating metastatic disease. We discuss the general options for treatment and recent developments in the field. PMID:26949522

  1. Prostate Cancer Genetics: A Review

    PubMed Central

    Wallis, Christopher J.D.

    2015-01-01

    Over the past decades, research has focussed on identifying the genetic underpinnings of prostate cancer. It has been recognized that a number of forms of genetic changes coupled with epigenetic and gene expression changes can increase the prediction to develop prostate cancer. This review outlines the role of somatic copy number alterations (SCNAs), structural rearrangements, point mutations, and single nucleotide polymorphisms (SNPs) as well as miRNAs. Identifying relevant genetic changes offers the ability to develop novel biomarkers to allow early and accurate detection of prostate cancer as well as provide risk stratification of patients following their diagnosis. The concept of personalized or individualized medicine has gained significant attention. Therefore, a better understanding of the genetic and metabolic pathways underlying prostate cancer development offers the opportunity to explore new therapeutic interventions with the possibility of offering patient-specific targeted therapy.

  2. Expression of Nodal and Nodal Receptors in Prostate Stem Cells and Prostate Cancer Cells: Autocrine Effects on Cell Proliferation and Migration

    PubMed Central

    Vo, BaoHan T.; Khan, Shafiq A.

    2010-01-01

    BACKGROUND Nodal, a TGFβ like growth factor, functions as an embryonic morphogen that maintains the pluripotency of embryonic stem cells. Nodal has been implicated in cancer progression; however, there is no information on expression and functions of Nodal in prostate cancer. In this study, we have investigated the expression of Nodal, its receptors, and its effects on proliferation and migration of human prostate cells. METHODS RT-PCR, qPCR, and Western blot analyses were performed to analyze expression of Nodal and Nodal receptors and its effects on phosphorylation of Smad2/3 in prostate cells. The effects on proliferation and migration were determined by 3H-Thymidine incorporation and cell migration assays in the presence or absence of Nodal receptor inhibitor (SB431542). RESULTS Nodal was highly expressed in WPE, DU145, LNCaP, and LNCaP-C81 cells with low expression in RWPE1 and RWPE2 cells, but not in PREC, PC3 and PC3M cells. Nodal receptors are expressed at varying levels in all prostate cells. Treatment with exogenous Nodal induced phosphorylation of Smad2/3 in WPE, DU145, and PC3 cells, which was blocked by SB431542. Nodal dose-dependently inhibited proliferation of WPE, RWPE1 and DU145 cells, but not LNCaP and PC3 cells. Nodal induced cell migration in PC3 cells, which was inhibited by SB431542; Nodal had no effect on cell migration in WPE and DU145 cells. The effects of Nodal on cell proliferation and migration are mediated via ALK4 and ActRII/ActRIIB receptors and Smad 2/3 phosphorylation. CONCLUSIONS Nodal may function as an autocrine regulator of proliferation and migration of prostate cancer cells. PMID:21557273

  3. 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…

  4. IL-8 secretion in primary cultures of prostate cells is associated with prostate cancer aggressiveness

    PubMed Central

    Neveu, Bertrand; Moreel, Xavier; Deschênes-Rompré, Marie-Pier; Bergeron, Alain; LaRue, Hélène; Ayari, Cherifa; Fradet, Yves; Fradet, Vincent

    2014-01-01

    Background Chronic inflammation is believed to be a major factor in prostate cancer initiation and promotion and has been studied using prostate cancer cells and immortalized cell lines. However, little is known about the contribution of normal cells to the prostatic microenvironment and inflammation. We aim to study the contribution of normal prostate epithelial cells to prostate inflammation and to link the inflammatory status of normal cells to prostate cancer aggressiveness. Materials and methods Short-term primary cell cultures of normal epithelial prostate cells were derived from prostate biopsies from 25 men undergoing radical prostatectomy, cystoprostatectomy, or organ donation. Cells were treated with polyinosinic:polycytidylic acid, a mimic of double-stranded viral RNA and a potent inducer of the inflammatory response. Secretion of interleukin (IL)-8 in the cell culture medium by untreated and treated cells was measured and we determined the association between IL-8 levels in these primary cell cultures and prostate cancer characteristics. The Fligner–Policello test was used to compare the groups. Results Baseline and induced IL-8 secretion were highly variable between cultured cells from different patients. This variation was not related to drug use, past medical history, age, or preoperative prostate-specific antigen value. Nonetheless, an elevated secretion of IL-8 from normal cultured epithelial cells was associated with prostate cancer aggressiveness (P=0.0005). Conclusion The baseline secretion of IL-8 from normal prostate epithelial cells in culture is strongly correlated with cancer aggressiveness and may drive prostate cancer carcinogenesis. A better characterization of individual prostate microenvironment may provide a basis for personalized treatment and for monitoring the effects of strategies aimed at preventing aggressive prostate cancer. PMID:24892030

  5. 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

  6. Vitamin K2, a Naturally Occurring Menaquinone, Exerts Therapeutic Effects on Both Hormone-Dependent and Hormone-Independent Prostate Cancer Cells

    PubMed Central

    Samykutty, Abhilash; Shetty, Aditya V.; Dakshinamoorthy, Gajalakshmi; Zheng, Gouxing; Chen, Aoshuang; Bosland, Maarten C.; Kajdacsy-Balla, André; Gnanasekar, Munirathinam

    2013-01-01

    In recent years, several studies have shown that vitamin k2 (VK2) has anticancer activity in a variety of cancer cells. The antitumor effects of VK2 in prostate cancer are currently not known. In the present study, we sought to characterize the anticancer potential of VK2 in both androgen-dependent and -independent prostate cancer cells. Our investigations show that VK2 is able to suppress viability of androgen-dependent and androgen-independent prostate cancer cells via caspase-3 and -8 dependent apoptosis. We also show that VK2 treatment reduces androgen receptor expression and PSA secretion in androgen-dependent prostate cancer cells. Our results also implicate VK2 as a potential anti-inflammatory agent, as several inflammatory genes are downregulated in prostate cancer cells following treatment with VK2. Additionally, AKT and NF-kB levels in prostate cancer cells are reduced significantly when treated with VK2. These findings correlated with the results of the Boyden chamber and angiogenesis assay, as VK2 treatment reduced cell migration and angiogenesis potential of prostate cancer cells. Finally, in a nude mice model, VK2 administration resulted in significant inhibition of both androgen-dependent and androgen-independent tumor growth. Overall, our results suggest that VK2 may be a potential therapeutic agent in the treatment of prostate cancer. PMID:24062781

  7. 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.

  8. Cryotherapy for prostate cancer

    MedlinePlus

    ... the needles to the prostate gland. Then, very cold gas passes through the needles, creating ice balls that destroy the prostate gland. Warm salt water will flow through the catheter to keep your urethra (the tube from the bladder to ...

  9. 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.

  10. Prevention and management of osteoporosis in women with breast cancer and men with prostate cancer.

    PubMed

    Hershman, Dawn; Narayanan, Rashmi

    2004-07-01

    Advances in cancer treatment have resulted in improved life expectancies for survivors of breast and prostate cancer. As the number of cancer survivors grows, the long-term side effects of treatment play an increasingly prominent role in the routine care of these patients. Due to similar management approaches, survivors of breast and prostate cancer are at increased risk for osteoporosis. This review summarizes the prevention and management of osteoporosis and osteopenia resulting from cancer treatment in survivors of breast and prostate cancer.

  11. The effect of photon energy on intensity-modulated radiation therapy (IMRT) plans for prostate cancer

    PubMed Central

    Sung, Wonmo; Park, Jong Min; Choi, Chang Heon; Ha, Sung Whan

    2012-01-01

    Purpose To evaluate the effect of common three photon energies (6-MV, 10-MV, and 15-MV) on intensity-modulated radiation therapy (IMRT) plans to treat prostate cancer patients. Materials and Methods Twenty patients with prostate cancer treated locally to 81.0 Gy were retrospectively studied. 6-MV, 10-MV, and 15-MV IMRT plans for each patient were generated using suitable planning objectives, dose constraints, and 8-field setting. The plans were analyzed in terms of dose-volume histogram for the target coverage, dose conformity, organs at risk (OAR) sparing, and normal tissue integral dose. Results Regardless of the energies chosen at the plans, the target coverage, conformity, and homogeneity of the plans were similar. However, there was a significant dose increase in rectal wall and femoral heads for 6-MV compared to those for 10-MV and 15-MV. The V20 Gy of rectal wall with 6-MV, 10-MV, and 15-MV were 95.6%, 88.4%, and 89.4% while the mean dose to femoral heads were 31.7, 25.9, and 26.3 Gy, respectively. Integral doses to the normal tissues in higher energy (10-MV and 15-MV) plans were reduced by about 7%. Overall, integral doses in mid and low dose regions in 6-MV plans were increased by up to 13%. Conclusion In this study, 10-MV prostate IMRT plans showed better OAR sparing and less integral doses than the 6-MV. The biological and clinical significance of this finding remains to be determined afterward, considering neutron dose contribution. PMID:23120741

  12. Effects of Sorafenib on C-Terminally Truncated Androgen Receptor Variants in Human Prostate Cancer Cells

    PubMed Central

    Zengerling, Friedemann; Streicher, Wolfgang; Schrader, Andres J.; Schrader, Mark; Nitzsche, Bianca; Cronauer, Marcus V.; Höpfner, Michael

    2012-01-01

    Recent evidence suggests that the development of castration resistant prostate cancer (CRPCa) is commonly associated with an aberrant, ligand-independent activation of the androgen receptor (AR). A putative mechanism allowing prostate cancer (PCa) cells to grow under low levels of androgens, is the expression of constitutively active, C-terminally truncated AR lacking the AR-ligand binding domain (LBD). Due to the absence of a LBD, these receptors, termed ARΔLBD, are unable to respond to any form of anti-hormonal therapies. In this study we demonstrate that the multikinase inhibitor sorafenib inhibits AR as well as ARΔLBD-signalling in CRPCa cells. This inhibition was paralleled by proteasomal degradation of the AR- and ARΔLBD-molecules. In line with these observations, maximal antiproliferative effects of sorafenib were achieved in AR and ARΔLBD-positive PCa cells. The present findings warrant further investigations on sorafenib as an option for the treatment of advanced AR-positive PCa. PMID:23109869

  13. Effects of sorafenib on C-terminally truncated androgen receptor variants in human prostate cancer cells.

    PubMed

    Zengerling, Friedemann; Streicher, Wolfgang; Schrader, Andres J; Schrader, Mark; Nitzsche, Bianca; Cronauer, Marcus V; Höpfner, Michael

    2012-01-01

    Recent evidence suggests that the development of castration resistant prostate cancer (CRPCa) is commonly associated with an aberrant, ligand-independent activation of the androgen receptor (AR). A putative mechanism allowing prostate cancer (PCa) cells to grow under low levels of androgens, is the expression of constitutively active, C-terminally truncated AR lacking the AR-ligand binding domain (LBD). Due to the absence of a LBD, these receptors, termed ARΔLBD, are unable to respond to any form of anti-hormonal therapies. In this study we demonstrate that the multikinase inhibitor sorafenib inhibits AR as well as ARΔLBD-signalling in CRPCa cells. This inhibition was paralleled by proteasomal degradation of the AR- and ARΔLBD-molecules. In line with these observations, maximal antiproliferative effects of sorafenib were achieved in AR and ARΔLBD-positive PCa cells. The present findings warrant further investigations on sorafenib as an option for the treatment of advanced AR-positive PCa. PMID:23109869

  14. 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

  15. Anti-tumor effect of RGD modified PTX loaded liposome on prostatic cancer

    PubMed Central

    Cao, Yunjie; Zhou, Yaojun; Zhuang, Qianfeng; Cui, Li; Xu, Xianlin; Xu, Renfang; He, Xiaozhou

    2015-01-01

    In this study, we report an active targeting liposomal formulation directed by a novel peptide (RGD) that specifically binds to the integrins receptors overexpressed on prostatic cancer cells. The objectives of this study were to evaluate the in vitro and in vivo tumor drug targeting delivery of RGD modified liposomes on PC-3 cells and DU145 cells. The uptake efficiency of RGD-LP was 5.2 times higher than that of LP on PC-3 cells. The uptake efficiency of RGD-LP was 3.2 times higher than that of LP on DU145 cells. The anti-proliferative activity of RGD-LP-PTX against PC-3 cells and DU145 cells were much stronger compared to that of LP-PTX and free PTX, respectively. The tumor spheroids experiment revealed that RGD-LP-PTX was more efficaciously internalized into tumor spheroids than LP in both PC-3 cells and DU145 cells. Compared to LP-PTX and free PTX, RGD-LP-PTX showed the greatest tumor growth inhibitory effect in vivo. In brief, the RGD-LP may be an efficient targeting drug delivery system for prostatic cancer. PMID:26550128

  16. 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

  17. Evidence that Human Prostate Cancer is a ZIP1-Deficient Malignancy that could be Effectively Treated with a Zinc Ionophore (Clioquinol) Approach

    PubMed Central

    Costello, Leslie C; Franklin, Renty B; Zou, Jing; Naslund, Michael J

    2015-01-01

    Despite decades of research, no efficacious chemotherapy exists for the treatment of prostate cancer. Malignant prostate zinc levels are markedly decreased in all cases of prostate cancer compared to normal/benign prostate. ZIP1 zinc transporter down regulation decreases zinc to prevent its cytotoxic effects. Thus, prostate cancer is a “ZIP1-deficient” malignancy. A zinc ionophore (e.g. Clioquinol) treatment to increase malignant zinc levels is a plausible treatment of prostate cancer. However, skepticism within the clinical/biomedical research community impedes significant progress leading to such a zinc treatment. This report reviews the clinical and experimental background, and presents new experimental data showing Clioquinol suppression of prostate malignancy; which provides strong support for a zinc ionophore treatment for prostate cancer. Evaluation of often-raised opposing issues is presented. These considerations lead to the conclusion that the compelling evidence dictates that a zinc-treatment approach for prostate cancer should be pursued with additional research leading to clinical trials. PMID:26273543

  18. Prostate cancer: a serious disease suitable for prevention.

    PubMed

    Fitzpatrick, John M; Schulman, Claude; Zlotta, Alexandre R; Schröder, Fritz H

    2009-04-01

    Prostate cancer is among the most common causes of death from cancer in men, and accounts for 10% of all new male cancers worldwide. The diagnosis and treatment of prostate cancer place a substantial physical and emotional burden on patients and their families, and have considerable financial implications for healthcare providers and society. Given that the risk of prostate cancer continues to increase with age, the burden of the disease is likely to increase in line with population life-expectancy. Reducing the risk of prostate cancer has gained increasing coverage in recent years, with proof of principle shown in the Prostate Cancer Prevention Trial with the type 2 5alpha-reductase (5AR) inhibitor, finasteride. The long latency period, high disease prevalence, and significant associated morbidity and mortality make prostate cancer a suitable target for a risk-reduction approach. Several agents are under investigation for reducing the risk of prostate cancer, including selenium/vitamin E and selective oestrogen receptors modulators (e.g. toremifene). In addition, the Reduction by Dutasteride of Prostate Cancer Events trial, involving >8000 men, is evaluating the effect of the dual 5AR inhibitor, dutasteride, on the risk of developing prostate cancer. A successful risk-reduction strategy might decrease the incidence of the disease, as well as the anxiety, cost and morbidity associated with its diagnosis and treatment. PMID:19302133

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

    ClinicalTrials.gov

    2016-09-08

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

  20. 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

  1. African American Men and Prostate Cancer

    MedlinePlus Videos and Cool Tools

    ... have one of the highest incidences of prostate cancer in the world, and in this country the ... an epidemic. Winston Dyer: My introduction to prostate cancer started with the death of my 46-year- ...

  2. Leptin increases prostate cancer aggressiveness.

    PubMed

    López Fontana, Constanza M; Maselli, María E; Pérez Elizalde, Rafael F; Di Milta Mónaco, Nicolás A; Uvilla Recupero, Ana L; López Laur, José D

    2011-12-01

    Recent studies indicate that adipose tissue and adipocytokines might affect the development of prostate cancer (PCa). Leptin would have a stimulating effect on prostate cancer cells by inducing promotion and progression, whereas adiponectin would have a protective effect. The aim of this study was to determine the relation between body composition, leptin, and adiponectin levels with the prevalence and aggressiveness of PCa in men of Mendoza, Argentina. Seventy volunteers between 50 and 80 years (35 healthy men as control group and 35 with PCa) were selected. The PCa group was subclassified according to the Gleason Score (GS). Digital rectal examination, transrectal ultrasound, and prostatic biopsy were performed; PSA, testosterone, leptin, and adiponectin levels were determined; and a nutritional interview including anthropometric measurements and a food frequency questionnaire was carried out. Statistical analysis was performed by Student t test, ANOVA I, and Bonferroni (p < 0.05). Body mass index and percentage of body fat mass were not statistically different between PCa and control groups. However, body fat mass was higher in subjects with more aggressive tumors (p = 0.032). No differences were observed regarding leptin levels between the groups. Nevertheless, leptin levels were higher in subjects with high GS (p < 0.001). Adiponectin levels showed no statistical differences regarding the presence and aggressiveness of the tumor (p = 0.131). Finally, consumption and nutrient intake did not differ in the studied groups. In conclusion, body composition and leptin are related to the PCa aggressiveness but not with its prevalence.

  3. 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.

  4. Fortifying the Treatment of Prostate Cancer with Physical Activity

    PubMed Central

    Champ, Colin E.; Francis, Lanie; Klement, Rainer J.; Dickerman, Roger; Smith, Ryan P.

    2016-01-01

    Over the past decade, significant data have shown that obese men experience a survival detriment after treatment for prostate cancer. While methods to combat obesity are of utmost importance for the prostate cancer patient, newer data reveal the overall metabolic improvements that accompany increased activity levels and intense exercise beyond weight loss. Along these lines, a plethora of data have shown improvement in prostate cancer-specific outcomes after treatment accompanied with these activity levels. This review discusses the metabolic mechanisms in which increased activity levels and exercise can help improve both outcomes for men treated for prostate cancer while lowering the side effects of treatment. PMID:26977321

  5. 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.

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

    PubMed

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

    2013-05-01

    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.

  7. [Castration resistant prostate cancer 2015].

    PubMed

    Merseburger, A S; Böker, A; Kuczyk, M A; von Klot, C-A

    2015-01-01

    Prostate cancer is still the most common urological cancer of the elderly man. In some patients, a metastatic prostate cancer arises which may remain a stable disease for years with palliative antiandrogen therapy. On average, after 3-4 years, affected men develop a PSA rise and disease progression with the formation of a so-called castration-resistant disease. 5 years ago cytotoxic chemotherapy with docetaxel was the only life-prolonging treatment option in this situation. In the last 5 years, the results of randomised phase III studies have led to the approval of 5 new agents for the treatment of metastatic castration resistant prostate cancer (mCRPC). The results and approval status of the substances, Abiraterone, Enzalutamide, Cabazitaxel, Sipuleucel-T and radium-223 are described below. In addition, some aspects of sequential therapy and possible future molecular approaches are discussed. PMID:25658232

  8. Folate and B12 in prostate cancer.

    PubMed

    Collin, Simon M

    2013-01-01

    Mechanisms postulated to link folate and B12 metabolism with cancer, including genome-wide hypomethylation, gene-specific promoter hypermethylation, and DNA uracil misincorporation, have been observed in prostate tumor cells. However, epidemiological studies of prostate cancer risk, based on dietary intakes and blood levels of folate and vitamin B12 and on folate-pathway gene variants, have generated contradictory findings. In a meta-analysis, circulating concentrations of B12 (seven studies, OR = 1.10; 95% CI 1.01, 1.19; P = 0.002) and (in cohort studies) folate (five studies, OR = 1.18; 95% CI 1.00, 1.40; P = 0.02) were positively associated with an increased risk of prostate cancer. Homocysteine was not associated with risk of prostate cancer (four studies, OR = 0.91; 95% CI 0.69, 1.19; P = 0.5). In a meta-analysis of folate-pathway polymorphisms, MTR 2756A > G (eight studies, OR = 1.06; 95% CI 1.00, 1.12; P = 0.06) and SHMT1 1420C > T (two studies, OR = 1.11; 95% CI 1.00, 1.22; P = 0.05) were positively associated with prostate cancer risk. There were no effects due to any other polymorphisms, including MTHFR 677C > T (12 studies, OR = 1.04; 95% CI 0.97, 1.12; P = 0.3). The positive association of circulating B12 with an increased risk of prostate cancer could be explained by reverse causality. However, given current controversies over mandatory B12 fortification, further research to eliminate a causal role of B12 in prostate cancer initiation and/or progression is required. Meta-analysis does not entirely rule out a positive association of circulating folate with increased prostate cancer risk. As with B12, even a weak positive association would be a significant public health issue, given the high prevalence of prostate cancer and concerns about the potential harms versus benefits of mandatory folic acid fortification.

  9. 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.

  10. 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.

  11. Prostate Cancer Imaging with Novel PET Tracers.

    PubMed

    Lindenberg, Liza; Choyke, Peter; Dahut, William

    2016-03-01

    Molecular imaging of prostate cancer is in a dynamic phase of development. Currently approved techniques are limited and researchers have been working on novel agents to improve accuracy in targeting and detecting prostate tumors. In addition, the complexity of various prostate cancer states also contributes to the challenges in evaluating suitable radiotracer candidates. We have highlighted nuclear medicine tracers that focus on mechanisms involved in bone metastasis, prostate cancer cell membrane synthesis, amino acid analogs, androgen analogs, and the prostate specific membrane antigen. Encouraging results with many of these innovative radiotracer compounds will not only advance diagnostic capabilities for prostate cancer but open opportunities for theranostic applications to treat this worldwide malignancy.

  12. Selenium and Vitamin E: Cell Type– and Intervention-Specific Tissue Effects in Prostate Cancer

    PubMed Central

    Tsavachidou, Dimitra; McDonnell, Timothy J.; Wen, Sijin; Wang, Xuemei; Vakar-Lopez, Funda; Pisters, Louis L.; Pettaway, Curtis A.; Wood, Christopher G.; Do, Kim-Anh; Thall, Peter F.; Stephens, Clifton; Efstathiou, Eleni; Taylor, Robert; Menter, David G.; Troncoso, Patricia; Lippman, Scott M.; Logothetis, Christopher J.

    2009-01-01

    Background Secondary analyses of two randomized, controlled phase III trials demonstrated that selenium and vitamin E could reduce prostate cancer incidence. To characterize pharmacodynamic and gene expression effects associated with use of selenium and vitamin E, we undertook a randomized, placebo-controlled phase IIA study of prostate cancer patients before prostatectomy and created a preoperative model for prostatectomy tissue interrogation. Methods Thirty-nine men with prostate cancer were randomly assigned to treatment with 200 μg of selenium, 400 IU of vitamin E, both, or placebo. Laser capture microdissection of prostatectomy biopsy specimens was used to isolate normal, stromal, and tumor cells. Gene expression in each cell type was studied with microarray analysis and validated with a real-time polymerase chain reaction (PCR) and immunohistochemistry. An analysis of variance model was fit to identify genes differentially expressed between treatments and cell types. A beta-uniform mixture model was used to analyze differential expression of genes and to assess the false discovery rate. All statistical tests were two-sided. Results The highest numbers of differentially expressed genes by treatment were 1329 (63%) of 2109 genes in normal epithelial cells after selenium treatment, 1354 (66%) of 2051 genes in stromal cells after vitamin E treatment, and 329 (56%) of 587 genes in tumor cells after combination treatment (false discovery rate = 2%). Validation of 21 representative genes across all treatments and all cell types yielded Spearman correlation coefficients between the microarray analysis and the PCR validation ranging from 0.64 (95% confidence interval [CI] = 0.31 to 0.79) for the vitamin E group to 0.87 (95% CI = 0.53 to 0.99) for the selenium group. The increase in the mean percentage of p53-positive tumor cells in the selenium-treated group (26.3%), compared with that in the placebo-treated group (5%), showed borderline statistical significance

  13. 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

  14. Prostate Cancer Screening

    MedlinePlus

    ... Laboratory for Cancer Research Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer ... Centers Frederick National Lab Partners & Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer ...

  15. Prostate cancer in Asian men.

    PubMed

    Ito, Kazuto

    2014-04-01

    Prostate cancer incidence and mortality in most native Asian populations have gradually increased, but are around one-third lower than in corresponding Asian-American cohorts, which are themselves lower than the rates observed in other American cohorts. Although genetic and environmental factors, particularly a Western diet, could partially explain these differences, lower exposure to PSA screening in Asian individuals might be a major contributing factor. Genetic features and diet are, however, unlikely to differ substantially within the same region of Asia, and age-stratified PSA levels in men from various Asian countries are almost identical; therefore, variation in the epidemiology of prostate cancer among native Asian populations might be attributable to differences in access to PSA testing, urology clinics, and available therapies. Conversely, the proportion of patients with metastatic prostate cancer is substantially higher even in the more developed Asian countries than in migratory Asian populations residing in Western countries and in Westerners. Consequently, the most appropriate approaches to the management of prostate cancer in Asian countries probably also differ, and therefore individualized prostate cancer screening and treatment strategies based on the epidemiological features and socioeconomic status of each country are needed.

  16. 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

  17. 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. PMID:26121643

  18. PET/CT AND RADIOIMMUNOTHERAPY OF PROSTATE CANCER

    PubMed Central

    Bouchelouche, Kirsten; Capala, Jacek; Oehr, Peter

    2009-01-01

    Purpose of review Traditional morphologically based imaging modalities are now being complemented by positron emission tomography (PET)/computerized tomography (CT) in prostate cancer. Metastatic prostate cancer is an attractive target for radioimmunotherapy (RIT) since no effective therapies are available. This review highlights the most important achievements within the last year in PET/CT and RIT of prostate cancer. Recent findings Conflicting results exist on the use of choline for detection of malignant disease in the prostate gland. The role of PET/CT in N-staging remains to be elucidated further. However, 18F-choline and 11C-choline PET/CT have been demonstrated to be useful for detection of recurrence. 18F-choline and 18F-fluoride PET/CT are useful for detection of bone metastases. Prostate tumor antigens may be used as targets for RIT. Prostate specific membrane antigen (PSMA) is currently under focus of a number of diagnostic and therapeutic strategies. J591, a monoclonal antibody, that targets the extracellular domain of PSMA, shows promising results. HER2 receptors may also have a potential as target for PET/CT imaging and RIT of advanced prostate cancer. Summary PET/CT in prostate cancer has proven to play a significant role, in particular for detection of prostate cancer recurrence and bone metastases. Radioimmunotherapy of metastatic prostate cancer warrant further investigations. PMID:19535981

  19. Longitudinal Effects of Social Support and Adaptive Coping on the Emotional Well-Being of Survivors of Localized Prostate Cancer

    PubMed Central

    Zhou, Eric S.; Penedo, Frank J.; Bustillo, Natalie E.; Benedict, Catherine; Rasheed, Mikal; Lechner, Suzanne; Soloway, Mark; Kava, Bruce R.; Schneiderman, Neil; Antoni, Michael H.

    2010-01-01

    Survivors of prostate cancer experience treatment-related physical side effects that can compromise emotional well-being for years post treatment. There is limited research investigating how social support and the use of coping may affect the emotional well-being of this population following treatment. The aim of this study was to investigate how social support and coping impact emotional well-being 2 years after treatment in survivors of localized prostate cancer who have received either radical prostatectomy or radiotherapy. Psychosocial and disease-specific measures were administered to an ethnically and demographically diverse sample of 180 men treated for localized prostate cancer at baseline and at 2-year follow-up. Regression analyses demonstrated that higher levels of social support at baseline predicted better emotional well-being 2 years later. Furthermore, higher levels of adaptive coping at baseline partially mediated the relationship between social support and emotional well-being. Supportive relationships may contribute to improved emotional well-being following treatment by facilitating the use of adaptive coping strategies. Attention should be given to strengthening social support networks and educating survivors of prostate cancer on adaptive coping techniques. PMID:21086876

  20. 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

  1. 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.

  2. DNA damage phenotype and prostate cancer risk

    PubMed Central

    Kosti, O.; Goldman, L.; Saha, D.T.; Orden, R.A.; Pollock, A.J.; Madej, H.L.; Hsing, A.W.; Chu, L.W.; Lynch, J.H.; Goldman, R.

    2010-01-01

    The capacity of an individual to process DNA damage is considered a crucial factor in carcinogenesis. The comet assay is a phenotypic measure of the combined effects of sensitivity to a mutagen exposure and repair capacity. In this paper, we evaluate the association of the DNA repair kinetics, as measured by the comet assay, with prostate cancer risk. In a pilot study of 55 men with prostate cancer, 53 men without the disease, and 71 men free of cancer at biopsy, we investigated the association of DNA damage with prostate cancer risk at early (0-15 min) and later (15-45 min) stages following gamma-radiation exposure. Although residual damage within 45 min was the same for all groups (65% of DNA in comet tail disappeared), prostate cancer cases had a slower first phase (38% vs 41%) and faster second phase (27% vs 22%) of the repair response compared to controls. When subjects were categorized into quartiles, according to efficiency of repairing DNA damage, high repair-efficiency within the first 15 min after exposure was not associated with prostate cancer risk while higher at the 15-45 min period was associated with increased risk (OR for highest-to-lowest quartiles = 3.24, 95% CI=0.98-10.66, p-trend =0.04). Despite limited sample size, our data suggest that DNA repair kinetics marginally differ between prostate cancer cases and controls. This small difference could be associated with differential responses to DNA damage among susceptible individuals. PMID:21095241

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. Prostate cancer radiotherapy 2002: the way forward.

    PubMed

    Lukka, Himu; Pickles, Tom; Morton, Gerard; Catton, Charles; Souhami, Luis; Warde, Padraig

    2005-02-01

    In November 2000, the GU Radiation Oncologists of Canada had their first meeting, "Controversies in prostate cancer radiotherapy: consensus development". The success of this meeting prompted a second meeting, held in December 2002 to discuss "The Way Forward" in prostate radiotherapy. Radiation oncologists from across Canada were brought together and integrated with key opinion leaders in prostate cancer treatment from throughout North America. The group debated current controversies including: intensity modulated radiotherapy (IMRT), external beam hypofractionation, high dose-rate brachytherapy, and hormone therapy in the management of prostate cancer. The meeting also sought to identify and prioritize clinical trial opportunities and to highlight steps required to achieve these research goals. In summary, advances involving IMRT have enabled the use of higher radiation doses without increasing morbidity. With renewed interest in hypofractionated radiation schedules, the value of hypofractionation using IMRT was discussed and initial results from ongoing clinical trials were presented. The emerging role for high dose-rate brachytherapy in higher risk patients was also discussed. Based on existing preliminary evidence the group expressed enthusiasm for further investigation of the role for brachytherapy in intermediate to high-risk patients. Despite significant advances in radiotherapy, hormone therapy continues to play an important role in prostate cancer treatment for patients with intermediate and high-risk disease. Although evidence supports the effectiveness of hormone therapy, the optimal timing, and duration of hormonal treatment are unclear. Results from ongoing clinical trials will provide insight into these questions and will assist in the design of future clinical trials.

  8. Safety and chemopreventive effect of Polyphenon E in preventing early and metastatic progression of prostate cancer in TRAMP mice

    PubMed Central

    Kim, Seung Joon; Amankwah, Ernest; Connors, Shahnjayla; Park, Hyun Y.; Rincon, Maria; Cornnell, Heather; Chornokur, Ganna; Hashim, Arig Ibrahim; Choi, Junsung; Tsai, Ya-Yu; Engelman, Robert W.; Kumar, Nagi; Park, Jong Y.

    2014-01-01

    Background Prostate cancer treatment is often accompanied by untoward side effects. Therefore, chemoprevention to reduce the risk and inhibit the progression of prostate cancer may be an effective approach to reducing disease burden. We investigated the safety and efficacy of Polyphenon E, a green tea extract, in reducing the progression of prostate cancer in TRAMP mice. Methods 119 male TRAMP and 119 C57BL/6J mice were treated orally with one of three doses of Polyphenon E (200, 500, 1,000 mg/kg/day) in drinking water ad libitum replicating human achievable doses. Baseline assessments were performed prior to treatments. Safety and efficacy assessments during treatments were performed when mice were 12, 22 and 32 weeks old. Results The number and size of tumors in treated TRAMP mice were significantly decreased compared to untreated animals. In untreated 32 weeks old TRAMP mice, prostate carcinoma metastasis to distant sites was observed in 100% of mice (8/8), compared to 13% of mice (2/16) treated with high dose Polyphenon E during the same period. Further, Polyphenon E treatment significantly inhibited metastasis in TRAMP mice in a dose-dependent manner (P=0.0003). Long-term (32 weeks) treatment with Polyphenon E was safe and well tolerated with no evidence of toxicity in C57BL/6J mice. Conclusion Polyphenon E is an effective chemopreventive agent in preventing the progression of prostate cancer to metastasis in TRAMP mice. Polyphenon E showed no toxicity in these mouse models. Impact Our findings provide additional evidence for the safety and chemopreventive effect of Polyphenon E in preventing metastatic progression of PCa. PMID:24501325

  9. Evolving information needs among colon, breast, and prostate cancer survivors: Results from a longitudinal mixed-effects analysis

    PubMed Central

    Tan, Andy SL; Nagler, Rebekah H; Hornik, Robert C; DeMichele, Angela

    2015-01-01

    Background This study describes how cancer survivors’ information needs about recurrence, late effects, and family risks of cancer evolve over the course of their survivorship period. Methods Three annual surveys were conducted from 2006 to 2008 in a cohort of Pennsylvania cancer survivors diagnosed with colon, breast, or prostate cancer in 2005 (Round 1 N=2013, Round 2 N=1293, Round 3 N = 1,128). Outcomes were information seeking about five survivorship topics. Key predictors were survey round, cancer diagnosis, and the interaction between these variables. Mixed effects logistic regression analyses were performed to predict information seeking about each topic, adjusting for demographic variables, clinical characteristics, and clustering of repeated observations within individuals. Results Information seeking about reducing risks of cancer recurrence was the most frequently reported topic across survivors and over time. Breast cancer survivors were more likely to seek about survivorship topics at Round 1 compared with other survivors. In general, information seeking declined over time, but cancer-specific patterns emerged: the decline was sharpest for breast cancer survivors whereas in later years female colon cancer survivors actually sought more information (about how to reduce the risk of family members getting colon cancer or a different cancer). Conclusion Cancer survivors’ information needs varied over time depending on the topic, and these trends differed by cancer type. Impact Clinicians may need to intervene at distinct points during the survivorship period with information to address concerns about cancer recurrence, late effects, and family members’ risks. PMID:25979968

  10. 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

  11. CXCL5 Promotes Prostate Cancer Progression1

    PubMed Central

    Begley, Lesa A; Kasina, Sathish; Mehra, Rohit; Adsule, Shreelekha; Admon, Andrew J; Lonigro, Robert J; Chinnaiyan, Arul M; Macoska, Jill A

    2008-01-01

    CXCL5 is a proangiogenic CXC-type chemokine that is an inflammatory mediator and a powerful attractant for granulocytic immune cells. Unlike many other chemokines, CXCL5 is secreted by both immune (neutrophil, monocyte, and macrophage) and nonimmune (epithelial, endothelial, and fibroblastic) cell types. The current study was intended to determine which of these cell types express CXCL5 in normal and malignant human prostatic tissues, whether expression levels correlated with malignancy and whether CXCL5 stimulated biologic effects consistent with a benign or malignant prostate epithelial phenotype. The results of these studies show that CXCL5 protein expression levels are concordant with prostate tumor progression, are highly associated with inflammatory infiltrate, and are frequently detected in the lumens of both benign and malignant prostate glands. Exogenous administration of CXCL5 stimulates cellular proliferation and gene transcription in both nontransformed and transformed prostate epithelial cells and induces highly aggressive prostate cancer cells to invade through synthetic basement membrane in vitro. These findings suggest that the inflammatory mediator, CXCL5, may play multiple roles in the etiology of both benign and malignant proliferative diseases in the prostate. PMID:18320069

  12. 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…

  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. Psychological effects of androgen-deprivation therapy on men with prostate cancer and their partners.

    PubMed

    Donovan, Kristine A; Walker, Lauren M; Wassersug, Richard J; Thompson, Lora M A; Robinson, John W

    2015-12-15

    The clinical benefits of androgen-deprivation therapy (ADT) for men with prostate cancer (PC) have been well documented and include living free from the symptoms of metastases for longer periods and improved quality of life. However, ADT comes with a host of its own serious side effects. There is considerable evidence of the adverse cardiovascular, metabolic, and musculoskeletal effects of ADT. Far less has been written about the psychological effects of ADT. This review highlights several adverse psychological effects of ADT. The authors provide evidence for the effect of ADT on men's sexual function, their partner, and their sexual relationship. Evidence of increased emotional lability and depressed mood in men who receive ADT is also presented, and the risk of depression in the patient's partner is discussed. The evidence for adverse cognitive effects with ADT is still emerging but suggests that ADT is associated with impairment in multiple cognitive domains. Finally, the available literature is reviewed on interventions to mitigate the psychological effects of ADT. Across the array of adverse effects, physical exercise appears to have the greatest potential to address the psychological effects of ADT both in men who are receiving ADT and in their partners. PMID:26372364

  15. Psychological effects of androgen-deprivation therapy on men with prostate cancer and their partners.

    PubMed

    Donovan, Kristine A; Walker, Lauren M; Wassersug, Richard J; Thompson, Lora M A; Robinson, John W

    2015-12-15

    The clinical benefits of androgen-deprivation therapy (ADT) for men with prostate cancer (PC) have been well documented and include living free from the symptoms of metastases for longer periods and improved quality of life. However, ADT comes with a host of its own serious side effects. There is considerable evidence of the adverse cardiovascular, metabolic, and musculoskeletal effects of ADT. Far less has been written about the psychological effects of ADT. This review highlights several adverse psychological effects of ADT. The authors provide evidence for the effect of ADT on men's sexual function, their partner, and their sexual relationship. Evidence of increased emotional lability and depressed mood in men who receive ADT is also presented, and the risk of depression in the patient's partner is discussed. The evidence for adverse cognitive effects with ADT is still emerging but suggests that ADT is associated with impairment in multiple cognitive domains. Finally, the available literature is reviewed on interventions to mitigate the psychological effects of ADT. Across the array of adverse effects, physical exercise appears to have the greatest potential to address the psychological effects of ADT both in men who are receiving ADT and in their partners.

  16. Cellular and molecular mechanisms of pomegranate juice-induced anti-metastatic effect on prostate cancer cells.

    PubMed

    Wang, Lei; Alcon, Andre; Yuan, Hongwei; Ho, Jeffrey; Li, Qi-Jing; Martins-Green, M

    2011-07-01

    Prostate cancer is the second leading cause of cancer-related deaths among US males. Pomegranate juice (PJ), a natural product, was shown in a clinical trial to inhibit progression of this disease. However, the underlying mechanisms involved in the anti-progression effects of PJ on prostate cancer remain unclear. Here we show that, in addition to causing cell death of hormone-refractory prostate cancer cells, PJ also increases cell adhesion and decreases cell migration of the cells that do not die. We hypothesized that PJ does so by stimulating the expression and/or activation of molecules that alter the cytoskeleton and the adhesion machinery of prostate cancer cells, resulting in enhanced cell adhesion and reduced cell migration. We took an integrative approach to these studies by using Affimetrix gene arrays to study gene expression, microRNA arrays to study the non-coding RNAs, molecules known to be disregulated in cancer cells, and Luminex Multiplex array assays to study the level of secreted pro-inflammatory cytokines/chemokines. PJ up-regulates genes involved in cell adhesion such as E-cadherin, intercellular adhesion molecule 1 (ICAM-1) and down-regulates genes involved in cell migration such as hyaluranan-mediated motility receptor (HMMR) and type I collagen. In addition, anti-invasive microRNAs such as miR-335, miR-205, miR-200, and miR-126, were up-regulated, whereas pro-invasive microRNA such as miR-21 and miR-373, were down-regulated. Moreover, PJ significantly reduced the level of secreted pro-inflammatory cytokines/chemokines such as IL-6, IL-12p40, IL-1β and RANTES, thereby having the potential to decrease inflammation and its impact on cancer progression. PJ also inhibits the ability of the chemokine SDF1α to chemoattract these cancer cells. SDF1α and its receptor CXCR4 are important in metastasis of cancer cells to the bone. Discovery of the mechanisms by which this enhanced adhesion and reduced migration are accomplished can lead to

  17. miRNA Expression Analyses in Prostate Cancer Clinical Tissues

    PubMed Central

    Bucay, Nathan; Shahryari, Varahram; Majid, Shahana; Yamamura, Soichiro; Mitsui, Yozo; Tabatabai, Z. Laura; Greene, Kirsten; Deng, Guoren; Dahiya, Rajvir; Tanaka, Yuichiro; Saini, Sharanjot

    2015-01-01

    A critical challenge in prostate cancer (PCa) clinical management is posed by the inadequacy of currently used biomarkers for disease screening, diagnosis, prognosis and treatment. In recent years, microRNAs (miRNAs) have emerged as promising alternate biomarkers for prostate cancer diagnosis and prognosis. However, the development of miRNAs as effective biomarkers for prostate cancer heavily relies on their accurate detection in clinical tissues. miRNA analyses in prostate cancer clinical specimens is often challenging owing to tumor heterogeneity, sampling errors, stromal contamination etc. The goal of this article is to describe a simplified workflow for miRNA analyses in archived FFPE or fresh frozen prostate cancer clinical specimens using a combination of quantitative real-time PCR (RT-PCR) and in situ hybridization (ISH). Within this workflow, we optimize the existing methodologies for miRNA extraction from FFPE and frozen prostate tissues and expression analyses by Taqman-probe based miRNA RT-PCR. In addition, we describe an optimized method for ISH analyses formiRNA detection in prostate tissues using locked nucleic acid (LNA)- based probes. Our optimized miRNA ISH protocol can be applied to prostate cancer tissue slides or prostate cancer tissue microarrays (TMA). PMID:26382040

  18. miRNA Expression Analyses in Prostate Cancer Clinical Tissues.

    PubMed

    Bucay, Nathan; Shahryari, Varahram; Majid, Shahana; Yamamura, Soichiro; Mitsui, Yozo; Tabatabai, Z Laura; Greene, Kirsten; Deng, Guoren; Dahiya, Rajvir; Tanaka, Yuichiro; Saini, Sharanjot

    2015-01-01

    A critical challenge in prostate cancer (PCa) clinical management is posed by the inadequacy of currently used biomarkers for disease screening, diagnosis, prognosis and treatment. In recent years, microRNAs (miRNAs) have emerged as promising alternate biomarkers for prostate cancer diagnosis and prognosis. However, the development of miRNAs as effective biomarkers for prostate cancer heavily relies on their accurate detection in clinical tissues. miRNA analyses in prostate cancer clinical specimens is often challenging owing to tumor heterogeneity, sampling errors, stromal contamination etc. The goal of this article is to describe a simplified workflow for miRNA analyses in archived FFPE or fresh frozen prostate cancer clinical specimens using a combination of quantitative real-time PCR (RT-PCR) and in situ hybridization (ISH). Within this workflow, we optimize the existing methodologies for miRNA extraction from FFPE and frozen prostate tissues and expression analyses by Taqman-probe based miRNA RT-PCR. In addition, we describe an optimized method for ISH analyses formiRNA detection in prostate tissues using locked nucleic acid (LNA)- based probes. Our optimized miRNA ISH protocol can be applied to prostate cancer tissue slides or prostate cancer tissue microarrays (TMA). PMID:26382040

  19. miRNA Expression Analyses in Prostate Cancer Clinical Tissues.

    PubMed

    Bucay, Nathan; Shahryari, Varahram; Majid, Shahana; Yamamura, Soichiro; Mitsui, Yozo; Tabatabai, Z Laura; Greene, Kirsten; Deng, Guoren; Dahiya, Rajvir; Tanaka, Yuichiro; Saini, Sharanjot

    2015-09-08

    A critical challenge in prostate cancer (PCa) clinical management is posed by the inadequacy of currently used biomarkers for disease screening, diagnosis, prognosis and treatment. In recent years, microRNAs (miRNAs) have emerged as promising alternate biomarkers for prostate cancer diagnosis and prognosis. However, the development of miRNAs as effective biomarkers for prostate cancer heavily relies on their accurate detection in clinical tissues. miRNA analyses in prostate cancer clinical specimens is often challenging owing to tumor heterogeneity, sampling errors, stromal contamination etc. The goal of this article is to describe a simplified workflow for miRNA analyses in archived FFPE or fresh frozen prostate cancer clinical specimens using a combination of quantitative real-time PCR (RT-PCR) and in situ hybridization (ISH). Within this workflow, we optimize the existing methodologies for miRNA extraction from FFPE and frozen prostate tissues and expression analyses by Taqman-probe based miRNA RT-PCR. In addition, we describe an optimized method for ISH analyses formiRNA detection in prostate tissues using locked nucleic acid (LNA)- based probes. Our optimized miRNA ISH protocol can be applied to prostate cancer tissue slides or prostate cancer tissue microarrays (TMA).

  20. Screening spectroscopy of prostate cancer

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

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

  1. LOW RISK PROSTATE CANCER: ACTIVE TREATMENT OR ACTIVE SURVEILLANCE?

    PubMed

    Tomašković, Igor

    2015-09-01

    The widely used screening for prostate cancer with prostate specific antigen has resulted in identification of potentially lethal prostate cancers at a much more curable stage and has been associated with significant falls in prostate cancer mortality. In spite of the fact that prostate cancer is one of the deadliest malignancies in men, the advent of sensitive diagnostic testing has also resulted in detection of low risk cancers due to the high incidence of latent prostate cancer in aging men and prolonged natural history of the disease. This, in turn, has entailed the problem of cancer overdiagnosis and subsequent overtreatment. Approximately 6 times as many men will be diagnosed with the disease as will die from it. Active surveillance appeared as a response to the clearly documented risks of overdiagnosis and overtreatment of low risk prostate cancer for localized prostate cancer. It entails initial expectant management rather than immediate therapy, with 'curative-intent' treatment deferred until there is evidence that the patient is at an increased risk of disease progression. This approach attempts to balance the risks and side effects of overtreatment against the possibility of disease progression and lost opportunity for cure. A systematic literature review brings current knowledge on the subject.

  2. 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.

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

    PubMed

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

    2016-12-01

    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.

  4. Cost-effectiveness analysis comparing degarelix with leuprolide in hormonal therapy for patients with locally advanced prostate cancer.

    PubMed

    Hatoum, Hind T; Crawford, E David; Nielsen, Sandy Kildegaard; Lin, Swu-Jane; Marshall, Dennis C

    2013-04-01

    Degarelix, approved in the USA in 2008, is a gonadotropin-releasing hormone antagonist, representing one of the latest additions to androgen deprivation therapy (ADT). ADT is used as first-line therapy for locally advanced or metastatic prostate cancer with the aim to reduce testosterone to castrate levels. Like other gonadotropin-releasing hormone-antagonists, degarelix treatment results in rapid decrease in luteinizing hormone, follicle-stimulating hormone and testosterone levels without the associated risk of flare. Using one registration trial for degarelix with leuprolide as the active control, a cost-effectiveness analysis with a Markov model and a 20-year time horizon found the incremental cost-effectiveness ratio for degarelix to be US$245/quality-adjusted life years. Degarelix provides a cost-effective treatment for ADT among patients with locally advanced prostate cancer.

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

    PubMed

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

    2014-10-15

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

  6. 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

  7. 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.

  8. Effect of Increasing Radiation Doses on Local and Distant Failures in Patients With Localized Prostate Cancer

    SciTech Connect

    Kupelian, Patrick A. Ciezki, Jay; Reddy, Chandana A.; Klein, Eric A.; Mahadevan, Arul

    2008-05-01

    Purpose: To study the effect of radiation dose on local failure (LF) and distant metastasis (DM) in prostate cancer patients treated with external beam radiotherapy. Methods and Materials: The study sample consisted of 919 Stage T1-T3N0M0 patients treated with radiotherapy alone. Three separate dose groups were analyzed: <72 Gy (n = 552, median dose, 68.4 Gy), {>=}72 but <82 Gy (n = 215, median dose, 78 Gy), and {>=}82 Gy (n = 152, median dose, 83 Gy). The median follow-up period for all patients and those receiving <72 Gy, {>=}72 but <82 Gy, and {>=}82 Gy was 97, 112, 94, and 65 months, respectively. Results: For all patients, the LF rate at 10 and 15 years was 6% and 13%, respectively. The 7-year LF rate stratified by dose group (<72 Gy, {>=}72 but <82 Gy, and {>=}82 Gy) was 6%, 2%, and 2%, respectively (p 0.012). For all patients, the DM rate at 10 and 15 years was 10% and 17%, respectively. The 7-year DM rate stratified by dose group (<72 Gy, {>=}72 but <82 Gy, and {>=}82 Gy) was 9%, 6%, and 1%, respectively (p = 0.008). Multivariate analysis revealed T stage (p < 0.001), pretreatment prostate-specific antigen level (p = 0.001), Gleason score (p < 0.001), and dose (p = 0.018) to be independent predictors of DM. For all 919 patients, multivariate analysis revealed only Gleason score (p = 0.009) and dose (p 0.004) to be independent predictors of LF. Conclusion: Although the effect of increasing radiation doses has been documented mostly for biochemical failure rates, the results of our study have shown a clear association between greater radiation doses and lower LF and DM rates.

  9. Progress in prostate cancer imaging

    PubMed Central

    Gulley, James L.; Emberton, Mark; Kurhanewicz, John; Choyke, Peter

    2013-01-01

    There are multiple new technologies being developed for imaging of advanced prostate cancer. This Seminar article highlights several of these emerging modalities that were discussed at the Society of Urologic Oncology annual meeting in Bethesda, MD. © 2012 Elsevier Inc. All rights reserved. PMID:23218070

  10. Recent advances in imaging-guided interventions for prostate cancers

    PubMed Central

    Wu, Xia; Zhang, Feng; Chen, Ran; Zheng, Weiliang; Yang, Xiaoming

    2014-01-01

    The numbers of patients diagnosed with prostate cancers is increasing due to the widespread application of prostate-specific antigen screening and subsequent prostate biopsies. The methods of systemic administration of therapeutics are not target-specific and thus cannot efficiently destroy prostate tumour cells while simultaneously sparing the surrounding normal tissues and organs. Recent advances in imaging-guided minimally invasive therapeutic techniques offer considerable potential for the effective management of prostate cancers. An objective understanding of the feasibility, effectiveness, morbidity, and deficiencies of these interventional techniques is essential for both clinical practice and scientific progress. This review presents the recent advances in imaging-guided interventional techniques for the diagnosis and treatment of prostate cancers. PMID:24769076

  11. 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

  12. Prostate and Urologic Cancer | Division of Cancer Prevention

    Cancer.gov

    Conducts and supports research on the prevention and early detection of prostate and bladder cancer. | Conducts and supports research on the prevention and early detection of prostate, bladder, and skin cancers.

  13. 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.

  14. 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. PMID:18497085

  15. 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.

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

    MedlinePlus

    ... Next Topic Additional resources for 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 ...

  17. 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 ...

  18. Selenium level in benign and cancerous prostate.

    PubMed

    Zachara, Bronislaw A; Szewczyk-Golec, Karolina; Wolski, Zbigniew; Tyloch, Janusz; Skok, Zdzislaw; Bloch-Boguslawska, Elzbieta; Wasowicz, Wojciech

    2005-03-01

    The dietary microelement selenium (Se) has been proposed as a potential chemopreventive agent for prostate cancer. This element is present in various amounts in all tissues. Little information is available on Se level in patients with prostate gland disorders. The levels of Se in prostatic gland of patients with prostate cancer, benign prostate hyperplasia, and healthy controls were examined. The Se level for benign prostate hyperplasia (156 +/- 30.6 ng/g) was the same as in the control group (157 +/- 26.0 ng/g), but in the gland of prostate cancer patients (182 +/- 34.1 ng/g wet weight), the Se level was significantly (p < 0.01) higher than in both healthy controls and benign prostate hyperplasia. Thus, the Se level in human healthy controls is lower than in kidney and liver but higher compared with other tissues. PMID:15784953

  19. 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

  20. Antitumor effects of saffron-derived carotenoids in prostate cancer cell models.

    PubMed

    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.

  1. Antitumor effects of saffron-derived carotenoids in prostate cancer cell models.

    PubMed

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

    2014-01-01

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

  2. 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.

  3. Androgen receptors in prostate cancer.

    PubMed

    Culig, Z; Klocker, H; Bartsch, G; Hobisch, A

    2002-09-01

    The androgen receptor (AR), a transcription factor that mediates the action of androgens in target tissues, is expressed in nearly all prostate cancers. Carcinoma of the prostate is the most frequently diagnosed neoplasm in men in industrialized countries. Palliative treatment for non-organ-confined prostate cancer aims to down-regulate the concentration of circulating androgen or to block the transcription activation function of the AR. AR function during endocrine therapy was studied in tumor cells LNCaP subjected to long-term steroid depletion; newly generated sublines could be stimulated by lower concentrations of androgen than parental cells and showed up-regulation of AR expression and activity as well as resistance to apoptosis. Androgenic hormones regulate the expression of key cell cycle regulators, cyclin-dependent kinase 2 and 4, and that of the cell cycle inhibitor p27. Inhibition of AR expression could be achieved by potential chemopreventive agents flufenamic acid, resveratrol, quercetin, polyunsaturated fatty acids and interleukin-1beta, and by the application of AR antisense oligonucleotides. In the clinical situation, AR gene amplification and point mutations were reported in patients with metastatic disease. These mutations generate receptors which could be activated by other steroid hormones and non-steroidal antiandrogens. In the absence of androgen, the AR could be activated by various growth-promoting (growth factors, epidermal growth factor receptor-related oncogene HER-2/neu) and pleiotropic (protein kinase A activators, interleukin-6) compounds as well as by inducers of differentiation (phenylbutyrate). AR function is modulated by a number of coactivators and corepressors. The three coactivators, TIF-2, SRC-1 and RAC3, are up-regulated in relapsed prostate cancer. New experimental therapies for prostate cancer are aimed to down-regulate AR expression and to overcome difficulties which occur because of the acquisition of agonistic properties

  4. Targeting prostate cancer stem cells for cancer therapy

    PubMed Central

    Wang, Guocan; Wang, Zhiwei; Sarkar, Fazlul H.; Wei, Wenyi

    2012-01-01

    Prostate cancer (PCa) is the most common malignant neoplasm in men and the second most frequent cause of cancer death for males in the United States. Recently, emerging evidence suggests that prostate cancer stem cells (CSCs) may play a critical role in the development and progression of PCa. Therefore, targeting prostate CSCs for the prevention of tumor progression and treatment of PCa could become a novel strategy for better treatment of patients diagnosed with PCa. In this review article, we will summarize the most recent advances in the prostate CSCs field, with particular emphasis on targeting prostate CSCs to treat prostate cancer. PMID:22369972

  5. The high prevalence of undiagnosed prostate cancer at autopsy: implications for epidemiology and treatment of prostate cancer in the Prostate-specific Antigen-era.

    PubMed

    Jahn, Jaquelyn L; Giovannucci, Edward L; Stampfer, Meir J

    2015-12-15

    Widespread prostate-specific antigen (PSA) screening detects many cancers that would have otherwise gone undiagnosed. To estimate the prevalence of unsuspected prostate cancer, we reviewed 19 studies of prostate cancer discovered at autopsy among 6,024 men. Among men aged 70-79, tumor was found in 36% of Caucasians and 51% of African-Americans. This enormous prevalence, coupled with the high sensitivity of PSA screening, has led to the marked increase in the apparent incidence of prostate cancer. The impact of PSA screening on clinical practice is well-recognized, but its effect on epidemiologic research is less appreciated. Before screening, a larger proportion of incident prostate cancers had lethal potential and were diagnosed at advanced stage. However, in the PSA era, overall incident prostate cancer mainly is indolent disease, and often reflects the propensity to be screened and biopsied. Studies must therefore focus on cancers with lethal potential, and include long follow-up to accommodate the lead time induced by screening. Moreover, risk factor patterns differ markedly for potentially lethal and indolent disease, suggesting separate etiologies and distinct disease entities. Studies of total incident or indolent prostate cancer are of limited clinical utility, and the main focus of research should be on prostate cancers of lethal potential.

  6. Milk thistle and prostate cancer: differential effects of pure flavonolignans from Silybum marianum on antiproliferative end points in human prostate carcinoma cells.

    PubMed

    Davis-Searles, Paula R; Nakanishi, Yuka; Kim, Nam-Cheol; Graf, Tyler N; Oberlies, Nicholas H; Wani, Mansukh C; Wall, Monroe E; Agarwal, Rajesh; Kroll, David J

    2005-05-15

    Extracts from the seeds of milk thistle, Silybum marianum, are known commonly as silibinin and silymarin and possess anticancer actions on human prostate carcinoma in vitro and in vivo. Seven distinct flavonolignan compounds and a flavonoid have been isolated from commercial silymarin extracts. Most notably, two pairs of diastereomers, silybin A and silybin B and isosilybin A and isosilybin B, are among these compounds. In contrast, silibinin is composed only of a 1:1 mixture of silybin A and silybin B. With these isomers now isolated in quantities sufficient for biological studies, each pure compound was assessed for antiproliferative activities against LNCaP, DU145, and PC3 human prostate carcinoma cell lines. Isosilybin B was the most consistently potent suppressor of cell growth relative to either the other pure constituents or the commercial extracts. Isosilybin A and isosilybin B were also the most effective suppressors of prostate-specific antigen secretion by androgen-dependent LNCaP cells. Silymarin and silibinin were shown for the first time to suppress the activity of the DNA topoisomerase IIalpha gene promoter in DU145 cells and, among the pure compounds, isosilybin B was again the most effective. These findings are significant in that isosilybin B composes no more than 5% of silymarin and is absent from silibinin. Whereas several other more abundant flavonolignans do ultimately influence the same end points at higher exposure concentrations, these findings are suggestive that extracts enriched for isosilybin B, or isosilybin B alone, might possess improved potency in prostate cancer prevention and treatment.

  7. 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

  8. Inhibitory effects of antagonists of growth hormone-releasing hormone on growth and invasiveness of PC3 human prostate cancer.

    PubMed

    Muñoz-Moreno, Laura; Arenas, M Isabel; Schally, Andrew V; Fernández-Martínez, Ana B; Zarka, Elías; González-Santander, Marta; Carmena, María J; Vacas, Eva; Prieto, Juan C; Bajo, Ana M

    2013-02-15

    New approaches are needed to the therapy of advanced prostate cancer. This study determined the effect of growth hormone-releasing hormone (GHRH) antagonists, JMR-132 and JV-1-38 on growth of PC3 tumors as well as on angiogenesis and metastasis through the evaluation of various factors that contribute largely to the progression of prostate cancer. Human PC3 androgen-independent prostate cancer cells were injected subcutaneously into nude mice. The treatment with JMR-132 (10 μg/day) or JV-1-38 (20 μg/day) lasted 41 days. We also evaluated the effects of JMR-132 and JV-1-38 on proliferation, cell adhesion and migration in PC-3 cells in vitro. Several techniques (Western blot, reverse transcription polymerase chain reaction, immunohistochemistry, ELISA and zymography) were used to evaluate the expression levels of GHRH receptors and its splice variants, GHRH, vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF)-1α, metalloproteinases (MMPs) -2 and -9, β-catenin and E-cadherin. GHRH antagonists suppressed the proliferation of PC-3 cells in vitro and significantly inhibited growth of PC3 tumors. After treatment with these analogues, we found an increase in expression of GHRH receptor accompanied by a decrease of GHRH levels, a reduction in both VEGF and HIF-1α expression and in active forms of MMP-2 and MMP-9, a significant increase in levels of membrane-associated β-catenin and a significant decline in E-cadherin. These results support that the blockade of GHRH receptors can modulate elements involved in angiogenesis and metastasis. Consequently, GHRH antagonists could be considered as suitable candidates for therapeutic trials in the management of androgen-independent prostate cancer.

  9. 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. PMID:26282343

  10. Anticancer effect of deoxypodophyllotoxin induces apoptosis of human prostate cancer cells

    PubMed Central

    Hu, Sheng; Zhou, Qiang; Wu, Wan-Rui; Duan, Yi-Xing; Gao, Zhi-Yong; Li, Yuan-Wei; Lu, Qiang

    2016-01-01

    Deoxypodophyllotoxin (DPPT) is extracted and separated from citrus-related plants, including Podophyllum (P.) peltatum, P. pleianthum, P. emodi (also called P. hexandrum) and Diphylleia grayi. DPPT has significant antitumor and antiviral activity. However, due to its strong toxicity and side effects, its use is limited in practical applications. The in vitro antitumor efficacy of DPPT on human prostate cancer (PCa) cells remains to be determined. The present study investigated the anticancer effect of DPPT on human PCa cells and its potential mechanism. The data revealed that DPPT markedly reduced cell proliferation and activated the caspase-3 expression level by an increase in apoptotic cell death in DU-145 cells. In addition, treatment with DPPT markedly downregulated the levels of phosphorylated Akt and activated the p53/B-cell lymphoma 2 associated X protein (Bax)/phosphatase and tensin homolog (PTEN) signaling pathway in DU-145 cells, suggesting that caspase-mediated pathways were involved in DPPT-induced apoptosis. The present study suggested the role of DPPT as a novel chemotherapeutic drug for human PCa, which may function through the Akt/p53/Bax/PTEN signaling pathway. PMID:27698880

  11. Anticancer effect of deoxypodophyllotoxin induces apoptosis of human prostate cancer cells

    PubMed Central

    Hu, Sheng; Zhou, Qiang; Wu, Wan-Rui; Duan, Yi-Xing; Gao, Zhi-Yong; Li, Yuan-Wei; Lu, Qiang

    2016-01-01

    Deoxypodophyllotoxin (DPPT) is extracted and separated from citrus-related plants, including Podophyllum (P.) peltatum, P. pleianthum, P. emodi (also called P. hexandrum) and Diphylleia grayi. DPPT has significant antitumor and antiviral activity. However, due to its strong toxicity and side effects, its use is limited in practical applications. The in vitro antitumor efficacy of DPPT on human prostate cancer (PCa) cells remains to be determined. The present study investigated the anticancer effect of DPPT on human PCa cells and its potential mechanism. The data revealed that DPPT markedly reduced cell proliferation and activated the caspase-3 expression level by an increase in apoptotic cell death in DU-145 cells. In addition, treatment with DPPT markedly downregulated the levels of phosphorylated Akt and activated the p53/B-cell lymphoma 2 associated X protein (Bax)/phosphatase and tensin homolog (PTEN) signaling pathway in DU-145 cells, suggesting that caspase-mediated pathways were involved in DPPT-induced apoptosis. The present study suggested the role of DPPT as a novel chemotherapeutic drug for human PCa, which may function through the Akt/p53/Bax/PTEN signaling pathway.

  12. Current Perspectives in Prostate Cancer Vaccines

    PubMed Central

    Arlen, Philip M.; Gulley, James L.

    2012-01-01

    The use of vaccines as a potential therapeutic modality for the treatment of cancer has been extensively studied. Recent advances include identification and characterization of tumor-associated antigens, novel vaccine delivery systems, and the combination of vaccines with immune stimulants and other therapeutic modalities. Immunotherapy as a modality for treatment of prostate cancer has received significant attention. There are several characteristics of prostate cancer that make it an ideal target for immunotherapy. Prostate cancer’s relative indolence allows sufficient time to generate immune responses, which may take weeks or months to mount. In addition, prostate cancer-associated antigens direct the immune response to prostate cancer cells, thus sparing normal vital tissue. This review focuses on promising new vaccines and novel perspectives in the treatment of prostate cancer. PMID:19719454

  13. 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

  14. Phosphodiesterase 4D Inhibitors Limit Prostate Cancer Growth Potential

    PubMed Central

    Powers, Ginny L.; Hammer, Kimberly D.P.; Domenech, Maribella; Frantskevich, Katsiaryna; Malinowski, Rita L.; Bushman, Wade; Beebe, David J.; Marker, Paul C.

    2014-01-01

    Phosphodiesterase 4D (PDE4D) has recently been implicated as a proliferation-promoting factor in prostate cancer and is over-expressed in human prostate carcinoma. However, the effects of PDE4D inhibition using pharmacological inhibitors have not been examined in prostate cancer. These studies examined the effects of selective PDE4D inhibitors, NVP-ABE171 and cilomilast, as anti-prostate cancer therapies in both in vitro and in vivo models. The effects of PDE4D inhibitors on pathways that are critical in prostate cancer and/or downstream of cyclic AMP (cAMP) were examined. Both NVP-ABE171 and cilomilast decreased cell growth. In vitro, PDE4D inhibitors lead to decreased signaling of the sonic hedgehog (SHH), Androgen Receptor (AR), and MAPK pathways, but growth inhibition was best correlated to the sonic hedgehog pathway. PDE4D inhibition also reduced proliferation of epithelial cells induced by paracrine signaling from co-cultured stromal cells that had activated hedgehog signaling. In addition, PDE4D inhibitors decreased the weight of the prostate in wild-type mice. Prostate cancer xenografts grown in nude mice that were treated with cilomilast or NVP-ABE171 had decreased wet weight and increased apoptosis compared to vehicle treated controls. These studies suggest the pharmacological inhibition of PDE4D using small molecule inhibitors is an effective option for prostate cancer therapy. Implications PDE4D inhibitors decrease the growth of prostate cancer cells in vivo and in vitro, and PDE4D inhibition has therapeutic potential in prostate cancer. PMID:25149359

  15. Metformin and prostate cancer stem cells: a novel therapeutic target.

    PubMed

    Mayer, M J; Klotz, L H; Venkateswaran, V

    2015-12-01

    Prostate cancer is the second most frequently diagnosed cancer in the world. Localized disease can be effectively treated with radiation therapy or radical prostatectomy. However, advanced prostate cancer is more difficult to treat and if metastatic, is incurable. There is a need for more effective therapy for advanced prostate cancer. One potential target is the cancer stem cell (CSC). CSCs have been described in several solid tumors, including prostate cancer, and contribute to therapeutic resistance and tumor recurrence. Metformin, a common oral biguanide used to treat type 2 diabetes, has been demonstrated to have anti-neoplastic effects. Specifically, metformin targets CSCs in breast cancer, pancreatic cancer, glioblastoma and colon cancer. Metformin acts directly on the mitochondria to inhibit oxidative phosphorylation and reduce mitochondrial ATP production. This forces tumor cells to compensate by increasing the rate of glycolysis. CSCs rely heavily on mitochondrial oxidative phosphorylation for energy production. The glycolytic switch results in an energy crisis in these cells. Metformin could be used to exploit this metabolic weakness in CSCs. This would increase CSC sensitivity to conventional cancer therapies, circumventing treatment resistance and enhancing treatment efficacy. This review will explore the characteristics of prostate CSCs, their role in tumor propagation and therapeutic resistance and the role of metformin as a potential prostate CSC sensitizer to current anticancer therapies. PMID:26215782

  16. Metformin and prostate cancer stem cells: a novel therapeutic target.

    PubMed

    Mayer, M J; Klotz, L H; Venkateswaran, V

    2015-12-01

    Prostate cancer is the second most frequently diagnosed cancer in the world. Localized disease can be effectively treated with radiation therapy or radical prostatectomy. However, advanced prostate cancer is more difficult to treat and if metastatic, is incurable. There is a need for more effective therapy for advanced prostate cancer. One potential target is the cancer stem cell (CSC). CSCs have been described in several solid tumors, including prostate cancer, and contribute to therapeutic resistance and tumor recurrence. Metformin, a common oral biguanide used to treat type 2 diabetes, has been demonstrated to have anti-neoplastic effects. Specifically, metformin targets CSCs in breast cancer, pancreatic cancer, glioblastoma and colon cancer. Metformin acts directly on the mitochondria to inhibit oxidative phosphorylation and reduce mitochondrial ATP production. This forces tumor cells to compensate by increasing the rate of glycolysis. CSCs rely heavily on mitochondrial oxidative phosphorylation for energy production. The glycolytic switch results in an energy crisis in these cells. Metformin could be used to exploit this metabolic weakness in CSCs. This would increase CSC sensitivity to conventional cancer therapies, circumventing treatment resistance and enhancing treatment efficacy. This review will explore the characteristics of prostate CSCs, their role in tumor propagation and therapeutic resistance and the role of metformin as a potential prostate CSC sensitizer to current anticancer therapies.

  17. Testosterone Replacement Therapy and Prostate Cancer Incidence

    PubMed Central

    2015-01-01

    While early studies demonstrated a positive association between testosterone and prostate cancer, evidence on the nature of the relationship has evolved with time and newer data. Studies examining links between baseline testosterone levels as well as testosterone therapy and incident prostate cancer, reveal a more complex relationship. Moreover, investigators have reported their initial experiences with supplementing testosterone in men with a history of both treated and untreated prostate cancer. PMID:26770932

  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. 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.

  20. 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

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

    NASA Astrophysics Data System (ADS)

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

    2000-04-01

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

  2. Current Status of Biomarkers for Prostate Cancer

    PubMed Central

    Velonas, Vicki M.; Woo, Henry H.; dos Remedios, Cristobal G.; Assinder, Stephen J.

    2013-01-01

    Prostate cancer (PCa) is a leading cause of cancer-related death of men globally. Since its introduction, there has been intense debate as to the effectiveness of the prostate specific antigen (PSA) test as a screening tool for PCa. It is now evident that the PSA test produces unacceptably high rates of false positive results and is not prognostic. Here we review the current status of molecular biomarkers that promise to be prognostic and that might inform individual patient management. It highlights current efforts to identify biomarkers obtained by minimally invasive methods and discusses current knowledge with regard to gene fusions, mRNA and microRNAs, immunology, and cancer-associated microparticles. PMID:23708103

  3. Design of curcumin loaded cellulose nanoparticles for prostate cancer.

    PubMed

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

    2012-01-01

    Prostate cancer (PC) is the most frequently diagnosed disease in men in the United States. Curcumin (CUR), a natural diphenol, 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), hydroxypropyl methylcellulose (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 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.

  4. 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.

  5. Ethnic differences in prostate cancer

    PubMed Central

    Kheirandish, P; Chinegwundoh, F

    2011-01-01

    Background: It is recognised that the risk of prostate cancer is higher in black men than in white men worldwide. Recent studies suggest that a number of genetic mutations in black men predispose them to this disease; hence, race as well as environmental factors such as diet and migration are thought to be the determining factors. Methods: This review compares data from the United States (US), which suggest that African-American men have a 60% higher risk for developing prostate cancer with poorer prognosis in comparison with their white counterparts, with similar studies carried out in the United Kingdom (UK) and also in African and Caribbean countries. Conclusions: Studies from the United States and the United Kingdom came to significantly different conclusions, and this has implications for policy development, awareness raising among black men in each country and clinical practice. PMID:21829203

  6. Oxidative stress in prostate cancer.

    PubMed

    Khandrika, Lakshmipathi; Kumar, Binod; Koul, Sweaty; Maroni, Paul; Koul, Hari K

    2009-09-18

    As prostate cancer and aberrant changes in reactive oxygen species (ROS) become more common with aging, ROS signaling may play an important role in the development and progression of this malignancy. Increased ROS, otherwise known as oxidative stress, is a result of either increased ROS generation or a loss of antioxidant defense mechanisms. Oxidative stress is associated with several pathological conditions including inflammation and infection. ROS are products of normal cellular metabolism and play vital roles in stimulation of signaling pathways in response to changing intra- and extracellular environmental conditions. Chronic increases in ROS over time are known to induce somatic mutations and neoplastic transformation. In this review we summarize the causes for increased ROS generation and its potential role in etiology and progression of prostate cancer. PMID:19185987

  7. 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

  8. Vitamin D, sunlight, and the epidemiology of prostate cancer.

    PubMed

    Schwartz, Gary G

    2013-01-01

    The hypothesis that vitamin D deficiency increases the risk of clinical prostate cancer has stimulated an extensive body of research. Ecologic studies have shown that mortality rates from prostate cancer are inversely correlated with levels of ultraviolet radiation, the principal source of vitamin D. Human prostate cells express receptors for 1,25-Dihydroxyvitamin D which exerts pleitropic anticancer effects on these cells in vitro and in animal models. Moreover, normal prostate cells synthesize 1,25-Dihydroxyvitamin D from circulating levels of 25-OHD, whose levels are dependent on exposure to ultraviolet light. Analytic epidemiologic studies of vitamin D and prostate cancer have focused on polymorphisms in the vitamin D receptor (VDR), on serum vitamin D levels, and on solar exposure. A role for VDR polymorphisms in prostate cancer risk and progression is established. Prospective studies of serum 25(OH)D do not support a protective role for higher levels of 25(OH)D on prostate cancer risk overall, but a role for vitamin D deficiency is supported by several studies. Conversely, a growing body of evidence implicates low levels of 25-OHD with an increased risk of fatal prostate cancer. The results of most epidemiologic studies of sunlight exposure are consistent with a protective effect of exposure to ultraviolet radiation. The discrepancy between the results of studies of solar exposure and studies of serum 25-OHD may be related to methodological differences and to uncertainties regarding the critical period for vitamin D exposure. Additionally, both high dietary intake of calcium and high levels of calcium in serum are positively associated with prostate cancer risk. The relationship between serum 25(OH)D levels and risk of prostate cancer may differ by calcium intake.

  9. 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 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.

  10. 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

  11. Annatto Tocotrienol Induces a Cytotoxic Effect on Human Prostate Cancer PC3 Cells via the Simultaneous Inhibition of Src and Stat3.

    PubMed

    Sugahara, Ryosuke; Sato, Ayami; Uchida, Asuka; Shiozawa, Shinya; Sato, Chiaki; Virgona, Nantiga; Yano, Tomohiro

    2015-01-01

    Prostate cancer is one of the most frequently occurring cancers and often acquires the potential of androgen-independent growth as a malignant phenotype. Androgen-independent prostate cancer has severe chemoresistance towards conventional chemotherapeutic agents, so a new treatment approach is required for curing such prostate cancer. In this context, the present study was undertaken to check if annatto tocotrienol (main component δ-tocotrienol) could suppress cell growth in human prostate cancer (PC3, androgen-independent type) cells via the inhibition of Src and Stat3. The tocotrienol showed cytotoxic effects on PC3 cells in a dose-dependent manner, and the effect depended on G1 arrest in the cell cycle and subsequent induction of apoptosis. In a cytotoxic dose, the tocotrienol suppressed cellular growth via the simultaneous inhibition of Src and Stat3. Similarly, the treatment combination of both Src and Stat3 inhibitors induced cytotoxic effects in PC3 cells in an additive manner compared to each by itself. With respect to cell cycle regulation and the induction of apoptosis, the combination treatment showed a similar effect to that of the tocotrienol treatment. These results suggest that annatto tocotrienol effectively induces cytotoxicity in androgen-independent prostate cancer cells via the suppression of Src and Stat3. PMID:26875492

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

    PubMed Central

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

    2015-01-01

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

  13. Environmental exposures and prostate cancer.

    PubMed

    Mullins, Jeffrey K; Loeb, Stacy

    2012-01-01

    Many malignancies have been linked to specific environmental exposures. Several environmental and occupational factors have been studied for an association to prostate cancer (CaP) risk. These include Agent Orange exposure, farming and pesticides, sunlight/ultraviolet radiation, as well as trace minerals used in tire and battery manufacturing. This manuscript reviews the literature on these environmental exposures and CaP. PMID:22385992

  14. [Chemoprevention of prostate cancer - a plea].

    PubMed

    Schmitz-Dräger, B J; Bismarck, E; Schöffski, O; Fischer, C

    2012-05-01

    The high disease prevalence, the presentation in older age, a frequently slowly progressing course of disease, and high costs make the diagnosis of and therapy for prostate cancer a special challenge for urologists. Effective prevention of the disease may help to improve some of the problems mentioned above. Two randomised, controlled studies have proved that effective chemoprevention of prostate cancer is viable using 5α-reductase inhibitors (finasteride, dutasteride). Furthermore, there is increasing evidence that other compounds, e. g., selective oestrogen receptor modulators (SERMs), NSAIDs and statins might also be effective. This review investigates potential risks and benefits of chemoprevention including a consideration of health economical aspects. The authors conclude that the options of chemoprevention should be investigated in an open and unbiased way. PMID:22639024

  15. American Cancer Society prostate cancer survivorship care guidelines.

    PubMed

    Skolarus, Ted A; Wolf, Andrew M D; Erb, Nicole L; Brooks, Durado D; Rivers, Brian M; Underwood, Willie; Salner, Andrew L; Zelefsky, Michael J; Aragon-Ching, Jeanny B; Slovin, Susan F; Wittmann, Daniela A; Hoyt, Michael A; Sinibaldi, Victoria J; Chodak, Gerald; Pratt-Chapman, Mandi L; Cowens-Alvarado, Rebecca L

    2014-01-01

    Prostate cancer survivors approach 2.8 million in number and represent 1 in 5 of all cancer survivors in the United States. While guidelines exist for timely treatment and surveillance for recurrent disease, there is limited availability of guidelines that facilitate the provision of posttreatment clinical follow-up care to address the myriad of long-term and late effects that survivors may face. Based on recommendations set forth by a National Cancer Survivorship Resource Center expert panel, the American Cancer Society developed clinical follow-up care guidelines to facilitate the provision of posttreatment care by primary care clinicians. These guidelines were developed using a combined approach of evidence synthesis and expert consensus. Existing guidelines for health promotion, surveillance, and screening for second primary cancers were referenced when available. To promote comprehensive follow-up care and optimal health and quality of life for the posttreatment survivor, the guidelines address health promotion, surveillance for prostate cancer recurrence, screening for second primary cancers, long-term and late effects assessment and management, psychosocial issues, and care coordination among the oncology team, primary care clinicians, and nononcology specialists. A key challenge to the development of these guidelines was the limited availability of published evidence for management of prostate cancer survivors after treatment. Much of the evidence relies on studies with small sample sizes and retrospective analyses of facility-specific and population databases.

  16. Clarifying the positive association between education and prostate cancer: a Monte Carlo simulation approach.

    PubMed

    Pudrovska, Tetyana; Anishkin, Andriy

    2015-04-01

    Using the 1993-2011 data from the Wisconsin Longitudinal Study (N = 5,218), we examine prostate cancer screening, mortality after the diagnosis, and health behaviors as potential mechanisms explaining the paradoxical association between men's higher education and higher prostate cancer risk. Our study combines within-cohort longitudinal hazard models predicting a prostate cancer diagnosis with Monte Carlo simulations estimating the joint effects of socioeconomic differences in prostate cancer screening and mortality after the diagnosis. Our findings strongly suggest that higher utilization of prostate cancer screening and lower mortality after the diagnosis are important explanations for higher prostate rates among more educated men. In addition to applying an innovative method to the issues of prostate cancer incidence and survival, our results have potentially important implications for the current debate about the utility of prostate cancer screening as well as for accurate predictions of future mortality and morbidity trends in the expanding older population.

  17. [Testosterone replacement therapy and prostate cancer: the downfall of a paradigm?].

    PubMed

    Castillo, Octavio A; López-Fontana, Gastón; Vidal-Mora, Ivar; López Laur, José Daniel

    2015-04-06

    For six decades, it has been a part of the conventional medical wisdom that higher levels of testosterone increase the risk of prostate cancer. This belief is mostly derived from the well-documented regression of prostate cancer after surgical or pharmacological castration. However, there is an absence of scientific data supporting the concept that higher testosterone levels are associated with an increased risk of prostate cancer. Moreover, men with hypogonadism have substantial rates of prostate cancer in prostatic biopsies, suggesting that low testosterone has no protective effect against the development of prostate cancer. Moreover, prostate cancer rate is higher in elderly patients when hormonal levels are low. These results argue against an increased risk of prostate cancer with testosterone replacement therapy.

  18. Correlation between overexpression of EpCAM in prostate tissues and genesis of androgen-dependent prostate cancer.

    PubMed

    Xu, Yuan; Zhao, Hu; Hou, Jianquan

    2014-07-01

    The objective of this study was to investigate the role of epithelial cell adhesion molecule (EpCAM) in the genesis and the progress of prostate cancer, especially of castration-resistant prostate cancer. Protein expression of EpCAM in ten pairs of prostate cancer tissues and normal adjacent tissues, plus three cell lines, was examined. Short hairpin RNA (shRNA) interference technique was employed to silence the expression of EpCAM in prostate cancer cell LNCaP and construct a stable transfected cell line. In vitro assay was conducted to analyze the effect of EpCAM expression on the expressions of Androgen receptor (AR), Prostate specific antigen (PSA), and cellular proliferation and invasion. EpCAM was found significantly expressed higher in prostate cancer tissues than in normal adjacent tissues. In three cell lines (DU-145, PC-3, and LNCaP), the expression of EpCAM in LNCaP, androgen-dependent prostate cancer cells, was significantly higher than that in the other two. As EpCAM was silenced in LNCaP, the expression levels of AR and PSA obviously descended, and cellular abilities of proliferation and invasion were obviously inhibited.The overexpression of EpCAM has correlation with the genesis of prostate cancer, especially androgen-dependent prostate cancer. As the expression of AR is facilitated, prostate cancer cells' abilities to proliferate and invade are consequently enhanced.

  19. Promoter Methylation in Prostate Cancer and its Application for the Early Detection of Prostate Cancer Using Serum and Urine Samples

    PubMed Central

    Ahmed, Hafiz

    2010-01-01

    Prostate cancer is the second most common cancer and the second leading cause of cancer death in men. However, prostate cancer can be effectively treated and cured, if it is diagnosed in its early stages when the tumor is still confined to the prostate. Combined with the digital rectal examination, the PSA test has been widely used to detect prostate cancer. But, the PSA screening method for early detection of prostate cancer is not reliable due to the high prevalence of false positive and false negative results. Epigenetic alterations including hypermethylation of gene promoters are believed to be the early events in neoplastic progression and thus these methylated genes can serve as biomarkers for the detection of cancer from clinical specimens. This review discusses DNA methylation of several gene promoters during prostate carcinogenesis and evaluates the usefulness of monitoring methylated DNA sequences, such as GSTP1, RASSF1A, RARβ2 and galectin-3, for early detection of prostate cancer in tissue biopsies, serum and urine. PMID:20657713

  20. SOST Inhibits Prostate Cancer Invasion

    PubMed Central

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

    2015-01-01

    Inhibitors of Wnt signaling have been shown to be involved in prostate cancer (PC) metastasis; however the role of Sclerostin (Sost) has not yet been explored. Here we show that elevated Wnt signaling derived from Sost deficient osteoblasts promotes PC invasion, while rhSOST has an inhibitory effect. In contrast, rhDKK1 promotes PC elongation and filopodia formation, morphological changes characteristic of an invasive phenotype. Furthermore, rhDKK1 was found to activate canonical Wnt signaling in PC3 cells, suggesting that SOST and DKK1 have opposing roles on Wnt signaling in this context. Gene expression analysis of PC3 cells co-cultured with OBs exhibiting varying amounts of Wnt signaling identified CRIM1 as one of the transcripts upregulated under highly invasive conditions. We found CRIM1 overexpression to also promote cell-invasion. These findings suggest that bone-derived Wnt signaling may enhance PC tropism by promoting CRIM1 expression and facilitating cancer cell invasion and adhesion to bone. We concluded that SOST and DKK1 have opposing effects on PC3 cell invasion and that bone-derived Wnt signaling positively contributes to the invasive phenotypes of PC3 cells by activating CRIM1 expression and facilitating PC-OB physical interaction. As such, we investigated the effects of high concentrations of SOST in vivo. We found that PC3-cells overexpressing SOST injected via the tail vein in NSG mice did not readily metastasize, and those injected intrafemorally had significantly reduced osteolysis, suggesting that targeting the molecular bone environment may influence bone metastatic prognosis in clinical settings. PMID:26545120

  1. SOST Inhibits Prostate Cancer Invasion.

    PubMed

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

    2015-01-01

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

  2. Prostate cancer recurrence after Focal Therapy: Treatment options.

    PubMed

    Hamid, S; Guillaumier, S; Shah, T; Arya, M; Ahmed, H U

    2016-07-01

    Focal therapy is a novel treatment option in localised prostate cancer with or without a visible lesion on MRI. Treatment for low to intermediate risk prostate cancer with focal therapy has demonstrated good short to medium term outcomes with fewer undesirable genitourinary side effects. This has made focal therapy more appealing to men who find the implications of radical treatment unacceptable or are unable to tolerate active surveillance. In this paper we review the literature for treatment options in prostate cancer recurrence post focal therapy. We also cover the different definitions of failure agreed upon in previous consensus meetings, as well as their implications on future management focal therapy patients. PMID:27416641

  3. Prostate cancer: multiparametric MR imaging for detection, localization, and staging.

    PubMed

    Hoeks, Caroline M A; Barentsz, Jelle O; Hambrock, Thomas; Yakar, Derya; Somford, Diederik M; Heijmink, Stijn W T P J; Scheenen, Tom W J; Vos, Pieter C; Huisman, Henkjan; van Oort, Inge M; Witjes, J Alfred; Heerschap, Arend; Fütterer, Jurgen J

    2011-10-01

    This review presents the current state of the art regarding multiparametric magnetic resonance (MR) imaging of prostate cancer. Technical requirements and clinical indications for the use of multiparametric MR imaging in detection, localization, characterization, staging, biopsy guidance, and active surveillance of prostate cancer are discussed. Although reported accuracies of the separate and combined multiparametric MR imaging techniques vary for diverse clinical prostate cancer indications, multiparametric MR imaging of the prostate has shown promising results and may be of additional value in prostate cancer localization and local staging. Consensus on which technical approaches (field strengths, sequences, use of an endorectal coil) and combination of multiparametric MR imaging techniques should be used for specific clinical indications remains a challenge. Because guidelines are currently lacking, suggestions for a general minimal protocol for multiparametric MR imaging of the prostate based on the literature and the authors' experience are presented. Computer programs that allow evaluation of the various components of a multiparametric MR imaging examination in one view should be developed. In this way, an integrated interpretation of anatomic and functional MR imaging techniques in a multiparametric MR imaging examination is possible. Education and experience of specialist radiologists are essential for correct interpretation of multiparametric prostate MR imaging findings. Supportive techniques, such as computer-aided diagnosis are needed to obtain a fast, cost-effective, easy, and more reproducible prostate cancer diagnosis out of more and more complex multiparametric MR imaging data. PMID:21931141

  4. [Prostate cancer. Current and practice-relevant news from urology in 2011].

    PubMed

    Wirth, M; Zastrow, S

    2011-09-01

    The effect of 5α reductase inhibitors in prostate cancer has been extensively investigated. The studies determined that finasteride and also dutasteride reduced the risk of prostate cancer; however, particularly high-grade cancer was not reduced and may possibly even have been increased. This is appropriately reflected in the S3 guideline on prostate cancer. New data on early recognition show that after longer term observation prostate cancer-specific mortality can be more effectively reduced by screening than was initially shown by the original data from the ERSPC study. Active surveillance is becoming more important for the therapy of early prostate cancer. Other new publications have shown good results for patients who underwent surgery for high risk prostate cancer. For metastasized prostate cancer new immunotherapeutic, chemotherapeutic and hormonal options are now available or will soon be approved. PMID:21842194

  5. Prognostic factors in prostate cancer.

    PubMed

    Braeckman, Johan; Michielsen, Dirk

    2007-01-01

    In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before

  6. Prostate Cancer Imaging with Novel PET Tracers.

    PubMed

    Lindenberg, Liza; Choyke, Peter; Dahut, William

    2016-03-01

    Molecular imaging of prostate cancer is in a dynamic phase of development. Currently approved techniques are limited and researchers have been working on novel agents to improve accuracy in targeting and detecting prostate tumors. In addition, the complexity of various prostate cancer states also contributes to the challenges in evaluating suitable radiotracer candidates. We have highlighted nuclear medicine tracers that focus on mechanisms involved in bone metastasis, prostate cancer cell membrane synthesis, amino acid analogs, androgen analogs, and the prostate specific membrane antigen. Encouraging results with many of these innovative radiotracer compounds will not only advance diagnostic capabilities for prostate cancer but open opportunities for theranostic applications to treat this worldwide malignancy. PMID:26874530

  7. Prevention and Early Detection of Prostate Cancer

    PubMed Central

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

    2014-01-01

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

  8. Prostate Cancer Prevention: Concepts and Clinical Trials.

    PubMed

    Hamilton, Zachary; Parsons, J Kellogg

    2016-04-01

    Prevention is an important treatment strategy for diminishing prostate cancer morbidity and mortality and is applicable to both early- and late-stage disease. There are three basic classifications of cancer prevention: primary (prevention of incident disease), secondary (identification and treatment of preclinical disease), and tertiary (prevention of progression or recurrence). Based on level I evidence, 5-alpha reductase inhibitors (5-ARIs) should be considered in selected men to prevent incident prostate cancer. Level I evidence also supports the consideration of dutasteride, a 5-ARI, for tertiary prevention in active surveillance and biochemical recurrence patients. Vitamins and supplements, including selenium or vitamin E, have not been proven in clinical trials to prevent prostate cancer and in the case of Vitamin E has been found to increase the risk of incident prostate cancer. Ongoing and future trials may further elucidate the role of diet and immunotherapy for prevention of prostate cancer. PMID:26957512

  9. Focal Ablation of Prostate Cancer: Four Roles for MRI Guidance

    PubMed Central

    Sommer, Graham; Bouley, Donna; Gill, Harcharan; Daniel, Bruce; Pauly, Kim Butts; Diederich, Christopher

    2014-01-01

    Introduction There is currently a great deal of interest in the possible use of focal therapies for prostate cancer, since such treatments offer the prospect for control or cure of the primary disease with minimal side effects. Many forms of thermal therapy have been proposed for focal ablation of prostate cancer, including laser, high intensity ultrasound and cryotherapy. This review will demonstrate the important roles that MRI guidance can offer to such focal ablation, focusing on the use of high intensity ultrasonic applicators as an example of one promising technique. Materials and Methods Transurethral and interstitial high intensity ultrasonic applicators, designed specifically for ablation of prostate tissue were tested extensively in vivo in a canine model. The roles of MRI in positioning the devices, monitoring prostate ablation, and depicting ablated tissue were assessed using appropriate MRI sequences. Results MRI guidance provides a very effective tool for the positioning of ablative devices in the prostate, and thermal monitoring successfully predicted ablation of prostate tissue when a threshold of 52°C was achieved. Contrast enhanced MRI accurately depicted the distribution of ablated prostate tissue, which is resorbed at 30 days. Conclusions Guidance of thermal therapies for focal ablation of prostate cancer will likely prove critically dependent on MRI functioning in four separate roles. Our studies indicate that in 3 roles: device positioning; thermal monitoring of prostate ablation; and depiction of ablated prostate tissue, MR techniques are highly accurate and likely to be of great benefit in focal prostate cancer ablation. A fourth critical role, identification of cancer within the gland for targeting of thermal therapy, is more problematic at present, but will likely become practical with further technological advances. PMID:23587506

  10. Markers for Detection of Prostate Cancer

    PubMed Central

    Clarke, Raymond A.; Schirra, Horst J.; Catto, James W.; Lavin, Martin F.; Gardiner, Robert A.

    2010-01-01

    Early detection of prostate cancer is problematic, not just because of uncertainly whether a diagnosis will benefit an individual patient, but also as a result of the imprecise and invasive nature of establishing a diagnosis by biopsy. Despite its low sensitivity and specificity for identifying patients harbouring prostate cancer, serum prostate specific antigen (PSA) has become established as the most reliable and widely-used diagnostic marker for this condition. In its wake, many other markers have been described and evaluated. This review focuses on the supporting evidence for the most prominent of these for detection and also for predicting outcome in prostate cancer. PMID:24281110

  11. Imaging techniques for prostate cancer: implications for focal therapy

    PubMed Central

    Turkbey, Baris; Pinto, Peter A.; Choyke, Peter L.

    2012-01-01

    The multifocal nature of prostate cancer has necessitated whole-gland therapy in the past; however, since the widespread use of PSA screening, patients frequently present with less-advanced disease. Many men with localized disease wish to avoid the adverse effects of whole-gland therapy; therefore, focal therapy for prostate cancer is being considered as a treatment option. For focal treatment to be viable, accurate imaging is required for diagnosis, staging, and monitoring of treatment. Developments in MRI and PET have brought more attention to prostate imaging and the possibility of improving the accuracy of focal therapy. In this Review, we discuss the advantages and disadvantages of conventional methods for imaging the prostate, new developments for targeted imaging, and the possible role of image-guided biopsy and therapy for localized prostate cancer. PMID:19352394

  12. KLK-targeted Therapies for Prostate Cancer

    PubMed Central

    Johanna, Mattsson; Ulf-Håkan, Stenman

    2014-01-01

    Alternative treatments are urgently needed for prostate cancer, especially to address the aggressive metastatic castration-resistant disease. Proteolytic enzymes are involved in cancer growth and progression. The prostate produces several proteases, the most abundant ones being two members of the kallikrein-related peptidase (KLK) family, prostate-specific antigen (PSA) and KLK2. Despite the wide use of PSA as a clinical marker, the function(s) of PSA and other KLKs in prostate cancer are poorly known. Hypothetic roles of KLKs in prostate cancer include activities that may both promote and inhibit cancer growth and metastasis, including the antiangiogenic activity of PSA. Thus it may be possible to control prostate cancer growth by modulating the proteolytic activities of KLKs. PSA and KLK2 are especially attractive targets for prostate cancer treatment because of their proposed roles in tumor development and inhibition of angiogenesis in combination with their prostate selective expression. So far the number of molecules affecting selectively the activity of KLKs is limited and none of these are used to treat prostate cancer. Prodrugs that, after cleavage of the peptide part by PSA or KLK2, release active drug molecules, and PSA-targeted therapeutic vaccines have already been tested clinically in humans and the first results have been encouraging. Although KLKs are attractive targets for prostate cancer treatment, much remains to be done before their potential can be fully elucidated. The objective of this review is to address the current state of the KLKs as novel therapeutic targets for prostate cancer treatment.

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  15. Enhancing the effectiveness of androgen deprivation in prostate cancer by inducing Filamin A nuclear localization

    PubMed Central

    Mooso, Benjamin A.; Vinall, Ruth L.; Tepper, Clifford G.; Savoy, Rosalinda M.; Cheung, Jean P.; Singh, Sheetal; Siddiqui, Salma; Wang, Yu; Bedolla, Roble G.; Martinez, Anthony; Mudryj, Maria; Kung, Hsing-Jien; deVere White, Ralph W.; Ghosh, Paramita M.

    2013-01-01

    Since prostate cancer (CaP) is regulated by androgen receptor (AR) activity, metastatic CaP is treated with androgen deprivation therapy (ADT). Despite initial response, patients on ADT eventually progress to castration-resistant CaP (CRPC), which is currently incurable. We previously showed that cleavage of the 280kDa structural protein Filamin A (FlnA) to a 90kDa fragment, and nuclear localization of the cleaved product, sensitized CRPC cells to ADT. Hence, treatment promoting FlnA nuclear localization would enhance androgen responsiveness. Here, we show that FlnA nuclear localization induced apoptosis in CRPC cells during ADT, identifying it as a treatment tool in advanced CaP. Significantly, the natural product genistein-combined-polysaccharide (GCP) had a similar effect. Investigation of the mechanism of GCP-induced apoptosis showed that GCP induced FlnA cleavage and nuclear localization, and that apoptosis resulting from GCP treatment was mediated by FlnA nuclear localization. Two main components of GCP are genistein and daidzein: the ability of GCP to induce G2 arrest was due to genistein whereas sensitivity to ADT stemmed from daidzein; hence both were needed to mediate GCP's effects. FlnA cleavage is regulated by its phosphorylation; we show that ADT enhanced FlnA phosphorylation, which prevented its cleavage, whereas GCP inhibited FlnA phosphorylation, thereby sensitizing CaP cells to ADT. In a mouse model of CaP recurrence, GCP, but not vehicle, impeded relapse following castration; indicating that GCP, when administered with ADT, interrupted the development of CRPC. These results demonstrate the efficacy of GCP in promoting FlnA nuclear localization and enhancing androgen responsiveness in CaP. PMID:22993077

  16. Controversies in proton therapy for prostate cancer.

    PubMed

    Bryant, Curtis; Henderson, Randal H; Hoppe, Bradford S; Mendenhall, William M; Nichols, R Charles; Su, Zhong; Li, Zuofeng; Mendenhall, Nancy P

    2016-08-01

    Proton therapy (PT) for prostate cancer has been a subject of controversy over the past two decades. Because of its dosimetric advantages when compared to conventional radiation, PT has the potential to improve the therapeutic ratio in the management of prostate cancer by decreasing toxicity and improving disease control. Nevertheless, its higher costs and the current lack of level I evidence documenting improved clinical outcomes have led some to question its cost-effectiveness. A number of new PT centers have been built over the past decade, leading many stakeholders, including patients, physicians, and insurers, to demand comparative effectiveness data to support its current use. In this review, we summarize the results of recently published studies that support the safety and efficacy of PT in the treatment of prostate cancer. We also review the available cost-effectiveness data for PT and discuss the future of PT, including the current randomized trial comparing PT to intensity-modulated radiation therapy and the need for additional research that may help to establish the relative benefit of PT when compared to photon-based radiation therapy. PMID:27558255

  17. The chemomodulatory effects of glufosfamide on docetaxel cytotoxicity in prostate cancer cells

    PubMed Central

    Attia, Reem T.; Tolba, Mai F.; Trivedi, Ruchit; Tadros, Mariane G.; Arafa, Hossam M.M.

    2016-01-01

    Background. Glufosfamide (GLU) is a glucose conjugate of ifosfamide in which isophosphoramide mustard is glycosidically linked to the β-D-glucose molecule. Based on GLU structure, it is considered a targeted chemotherapy with fewer side effects. The main objective of the current study is to assess the cytotoxic potential of GLU for the first time in prostate cancer (PC) cells representing different stages of the tumor. Furthermore, this study examined the potential synergistic activity of GLU in combination with docetaxel (DOC). Methods. Two different cell lines were used, LNCaP and PC-3. Concentration-response curves were assessed. The tested groups per cell line were, control, GLU, DOC and combination. Treatment duration was 72 h. Cytotoxicity was assessed using sulforhodamine B (SRB) assay and half maximal inhibitory concentration (IC50) was calculated. Synergy analyses were performed using Calcusyn®software. Subsequent mechanistic studies included β-glucosidase activity assay, glucose uptake and apoptosis studies, namely annexin V-FITC assay and the protein expression of mitochondrial pathway signals including Bcl-2, Bax, Caspase 9 and 3 were assessed. Data are presented as mean ± SD; comparisons were carried out using one way analysis of variance (ANOVA) followed by Tukey-Kramer’s test for post hoc analysis. Results. GLU induced cytotoxicity in both cell lines in a concentration-dependent manner. The IC50 in PC-3 cells was significantly lower by 19% when compared to that of LNCaP cells. The IC50 of combining both drugs showed comparable effect to DOC in PC-3 but was tremendously lowered by 49% compared to the same group in LNCaP cell line. β-glucosidase activity was higher in LNCaP by about 67% compared to that determined in PC-3 cells while the glucose uptake in PC-3 cells was almost 2 folds that found in LNCaP cells. These results were directly correlated to the efficacy of GLU in each cell line. Treatment of PC cells with GLU as single agent or in

  18. Androgen deprivation therapy for prostate cancer.

    PubMed

    Singer, Eric A; Golijanin, Dragan J; Miyamoto, Hiroshi; Messing, Edward M

    2008-02-01

    Androgen deprivation continues to play a crucial role in the treatment of advanced and metastatic prostate cancer. In the 65 years since its use was first described, urologists and medical oncologists have developed new and innovative ways to manipulate the hypothalamic-pituitary-gonadal axis with the goal of alleviating symptoms and prolonging the life of men with prostate cancer. Despite the successes that androgen deprivation therapy has brought, each method and regimen possesses unique benefits and burdens, of which the clinician and patient must be cognizant. This review discusses the first-line androgen deprivation methods and regimens presently in use with special attention paid to their side effects and the management of them, as well as the question of when to initiate androgen deprivation therapy.

  19. Current early diagnostic biomarkers of prostate cancer

    PubMed Central

    Qu, Min; Ren, Shan-Cheng; Sun, Ying-Hao

    2014-01-01

    Prostate cancer (PCa) has become to have the highest incidence and the second mortality rate in western countries, affecting men's health to a large extent. Although prostate-specific antigen (PSA) was discovered to help diagnose the cancer in an early stage for decades, its specificity is relative low, resulting in unnecessary biopsy for healthy people and over-treatment for patients. Thus, it is imperative to identify more and more effective biomarkers for early diagnosis of PCa in order to distinguish patients from healthy populations, which helps guide an early treatment to lower disease-related mortality by noninvasive or minimal invasive approaches. This review generally describes the current early diagnostic biomarkers of PCa in addition to PSA and summarizes the advantages and disadvantages of these biomarkers. PMID:24830695

  20. Detection of DNA viruses in prostate cancer

    PubMed Central

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

    2016-01-01

    We tested prostatic secretions from men with and without prostate cancer (13 cases and 13 matched controls) or prostatitis (18 cases and 18 matched controls) with metagenomic sequencing. A large number (>200) of viral reads was only detected among four prostate cancer cases (1 patient each positive for Merkel cell polyomavirus, JC polyomavirus and Human Papillomavirus types 89 or 40, respectively). Lower numbers of reads from a large variety of viruses were detected in all patient groups. Our knowledge of the biology of the prostate may be furthered by the fact that DNA viruses are commonly shed from the prostate and can be readily detected by metagenomic sequencing of expressed prostate secretions. PMID:27121729

  1. Androgen receptor and immune inflammation in benign prostatic hyperplasia and prostate cancer

    PubMed Central

    Izumi, Kouji; Li, Lei; Chang, Chawnshang

    2014-01-01

    Both benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are frequent diseases in middle-aged to elderly men worldwide. While both diseases are linked to abnormal growth of the prostate, the epidemiological and pathological features of these two prostate diseases are different. BPH nodules typically arise from the transitional zone, and, in contrast, PCa arises from the peripheral zone. Androgen deprivation therapy alone may not be sufficient to cure these two prostatic diseases due to its undesirable side effects. The alteration of androgen receptor-mediated inflammatory signals from infiltrating immune cells and prostate stromal/epithelial cells may play key roles in those unwanted events. Herein, this review will focus on the roles of androgen/androgen receptor signals in the inflammation-induced progression of BPH and PCa. PMID:26594314

  2. Prostate Cancer Screening (Beyond the Basics)

    MedlinePlus

    ... complications of advanced disease. ● For men with an aggressive prostate cancer, the best chance for curing it ... body. However, many early-stage cancers are not aggressive, and the five-year survival will be nearly ...

  3. Is whole gland salvage cryotherapy effective as palliative treatment of haematuria in patients with locally advanced prostate cancer? Results of a preliminary case series

    PubMed Central

    Mucciardi, Giuseppe; Galì, Alessandro; Pappalardo, Rosa; Lembo, Francesco; Anastasi, Giuseppina; Butticè, Salvatore; Ascenti, Giorgio; Lugnani, Franco

    2015-01-01

    Objectives: Locally advanced prostate cancer may cause several complications such as haematuria, bladder outlet obstruction, and renal failure due to the ureteral obstruction. Various treatments have been suggested, including radiotherapy, antifibrinolytics, bladder irrigation with alum solution, transurethral surgery and angioembolization, none of which have proven effectiveness. In the last years cryoablation has become a valid therapeutic option for prostate cancer. In our experience we used this ‘new’ technique as haemostatic therapy. Methods: We selected four patients with gross haematuria affected by locally advanced hormone refractory prostate cancer, who had already been treated with primary radiotherapy. We used third-generation cryotherapy: under ultrasonographic guidance, we inserted six cryoprobes, two in each of the vascular pedicles reaching at least −60°C, and three thermometers. We then induced two freeze–thaw cycles. Results: After the operation the haematuria stopped in all patients and at 9-month follow up we observed a mean of four red cells (range three to five) in the urinary sediment with no evidence of bacteriuria. Prostate volume, prostate-specific antigen and postmicturition residue were significantly reduced. Qmax improved significantly too. Conclusion: Our experience has given us good results with minimal intra- and postoperative complications. We think that haemostatic cryotherapy as a palliative approach for locally advanced prostate cancer could represent a valid treatment option and more consideration could be given to its use. PMID:26425138

  4. Angiogenesis Inhibitors in the treatment of Prostate Cancer

    PubMed Central

    Kluetz, Paul G.; Figg, William D.; Dahut, William L.

    2009-01-01

    Importance of the Field Prostate carcinoma is the most common non-cutaneous malignancy in American men. The efficacy of docetaxel and prednisone in metastatic castrate-resistant prostate cancer (mCRPC) has been shown to improve overall survival however its effect is not durable highlighting the need for new therapies. Areas covered in this Review We will review the development of some of the leading compounds with direct and indirect anti-angiogenic activity in prostate cancer including antibodies to vascular endothelial growth factor and its receptors, small molecule inhibitors of downstream signaling, immunomodulatory drugs with anti-angiogenic activity, and compounds thought to directly inhibit or destroy vascular endothelial cells. What the reader will gain The reader will gain a basic understanding of the role of angiogenesis in prostate cancer growth and metastasis. Current and potential targets of angiogenesis and their corresponding drugs under development for prostate cancer are discussed. Take Home Message There are now multiple early phase clinical trials of anti-angiogenic agents alone or in combination in prostate cancer. Several of these are now in phase III development. Combined therapy with two or more anti-angiogenic compounds may improve the activity of either compound alone. Multiple targets in the angiogenesis pathway continue to be elucidated and should remain an active area of investigation for the treatment of prostate cancer. PMID:20088745

  5. Polymeric Nanoparticles for Targeted Radiosensitization of Prostate Cancer Cells

    PubMed Central

    Menon, Jyothi U.; Tumati, Vasu; Hsieh, Jer-Tsong; Nguyen, Kytai T.; Saha, Debabrata

    2014-01-01

    One of the many issues of using radiosensitizers in a clinical setting is timing daily radiation treatments to coincide with peak drug concentration in target tissue. To overcome this deficit, we have synthesized a novel nanoparticle system consisting of poly (lactic-co-glycolic acid) (PLGA) nanoparticles conjugated with prostate cancer cell penetrating peptide-R11 and encapsulated with a potent radio-sensitizer 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one (NU7441) to allow prostate cancer-specific targeting and sustained delivery over 3 weeks. Preliminary characterization studies showed that the R11-conjugated nanoparticles (R11-NU7441 NPs) had an average size of about 274 ± 80 nm and were stable for up to 5 days in de-ionized water and serum. The nanoparticles were cytocompatible with immortalized prostate cells (PZ-HPV-7). Further, the particles showed a bi-phasic release of encapsulated NU7441 and were taken up by PC3 prostate cancer cells in a dose- and magnetic field-dependent manner while not being taken up in non-prostate cancer cell lines. In addition, R11-NU7441 NPs were effective radiation sensitizers of prostate cancer cell lines in vitro. These results thus demonstrate the potential of R11-conjugated PLGA NPs as novel platforms for targeted radiosensitization of prostate cancer cells. PMID:25088162

  6. [Value of galvanotherapy for localised prostate cancer].

    PubMed

    Arsov, C; Winter, C; Albers, P

    2009-07-01

    In recent years electrotherapy has become an accepted treatment option in several medical subfields such as defibrillation during cardiopulmonary resuscitation, electroconvulsive shock treatment (ECT) in conjunction with antidepressant therapy, pain management and physical therapy [transcutaneous electrical nerve stimulation (TENS), diathermia, Stanger bath therapy, etc.]. In recent years several groups, especially from Asia, have investigated the therapeutic effect of electricity in the treatment of malignant tumours. They determined basic principles of electrotherapy and developed different theories of tumour destruction. They postulated a multifactorial tissue effect of continuous current based on tumour cell necrosis due to pH shifting and alteration of membrane potential. In clinical trials similar oncological results of electrotherapy in several malignant tumours compared to established therapeutic methods were observed, whereas clinical trial designs to some extent were not consistent with internationally accepted scientific standards. Regarding electrotherapy of localised prostate cancer only limited data with a few cases and controversial study designs were published. According to EAU guidelines electrotherapy of localised prostate cancer as an alternative treatment option is not recommended and is still an experimental method. For this procedure well-designed clinical trials and a longer follow-up are mandatory to assess the true role of electrotherapy in the management of prostate cancer.

  7. Detection of AR-V7 mRNA in whole blood may not predict the effectiveness of novel endocrine drugs for castration-resistant prostate cancer

    PubMed Central

    Takeuchi, Takumi; Okuno, Yumiko; Hattori-Kato, Mami; Zaitsu, Masayoshi; Mikami, Koji

    2016-01-01

    A splice variant of androgen receptor (AR), AR-V7, lacks in androgen-binding portion and leads to aggressive cancer characteristics. Reverse transcription-polymerase chain reactions (PCRs) and subsequent nested PCRs for the amplification of AR-V7 and prostate-specific antigen (PSA) transcripts were done for whole blood of patients with prostate cancer and male controls. With primary reverse transcription PCRs, AR-V7 and PSA were detected in 4.5% and 4.7% of prostate cancer, respectively. With nested PCRs, AR-V7 messenger RNA (mRNA) was positive in 43.8% of castration-sensitive prostate cancer and 48.1% of castration-resistant prostate cancer (CRPC), while PSA mRNA was positive in 6.3% of castration-sensitive prostate cancer and 18.5% of CRPC. Whole-blood samples of controls showed AR-V7 mRNA expression by nested PCR. Based on multivariate analysis, expression of AR-V7 mRNA in whole blood was not significantly correlated with clinical parameters and PSA mRNA in blood, while univariate analysis showed a correlation between AR-V7 mRNA and metastasis at initial diagnosis. Detection of AR-V7 mRNA did not predict the reduction of serum PSA in patients with CRPC following abiraterone and enzalutamide administration. In conclusion, AR-V7 mRNA expression in normal hematopoietic cells may have annihilated the manifestation of aggressiveness of prostate cancer and the prediction of the effectiveness of abiraterone and enzalutamide by the assessment of AR-V7 mRNA in blood. PMID:26870716

  8. Replication and cumulative effects of GWAS-identified genetic variations for prostate cancer in Asians: a case–control study in the ChinaPCa consortium

    PubMed Central

    Wang, Meilin; Liu, Fang; Hsing, Ann W.; Wang, Xiang; Shao, Qiang; Qi, Jun; Ye, Yu; Wang, Zhong; Chen, Hongyan; Gao, Xin; Wang, Guozeng; Chu, Lisa W.; Ding, Qiang; OuYang, Jun; Gao, Xu; Huang, Yichen; Chen, Yanbo; Gao, Yu-Tang; Zhang, Zuo-Feng; Rao, Jiangyu; Shi, Rong; Wu, Qijun; Zhang, Yuanyuan; Jiang, Haowen; Zheng, Jie; Hu, Yanlin; Guo, Ling; Lin, Xiaoling; Tao, Sha; Jin, Guangfu; Sun, Jielin; Lu, Daru; Zheng, S.Lilly; Sun, Yinghao; Mo, Zengnan; Yin, Changjun; Zhang, Zhengdong

    2012-01-01

    A recent genome-wide association study has identified five new genetic variants for prostate cancer susceptibility in a Japanese population, but it is unknown whether these newly identified variants are associated with prostate cancer risk in other populations, including Chinese men. We genotyped these five variants in a case–control study of 1524 patients diagnosed with prostate cancer and 2169 control subjects from the Chinese Consortium for Prostate Cancer Genetics (ChinaPCa). We found that three of the five genetic variants were associated with prostate cancer risk (P = 4.33 × 10−8 for rs12653946 at 5p15, 4.43 × 10−5 for rs339331 at 6q22 and 8.42 × 10−4 for rs9600079 at 13q22, respectively). A cumulative effect was observed in a dose-dependent manner with increasing numbers of risk variant alleles (Ptrend = 2.58 × 10−13), and men with 5–6 risk alleles had a 2-fold higher risk of prostate cancer than men with 0–2 risk alleles (odds ratio = 2.26, 95% confidence interval = 1.78–2.87). Furthermore, rs339331 T allele was significantly associated with RFX6 and GPRC6A higher messenger RNA expression, compared with the C allele. However, none of the variants was associated with clinical stage, Gleason score or family history. These results provide further evidence that the risk loci identified in Japanese men also contribute to prostate cancer susceptibility in Chinese men. PMID:22114074

  9. Detection of AR-V7 mRNA in whole blood may not predict the effectiveness of novel endocrine drugs for castration-resistant prostate cancer.

    PubMed

    Takeuchi, Takumi; Okuno, Yumiko; Hattori-Kato, Mami; Zaitsu, Masayoshi; Mikami, Koji

    2016-01-01

    A splice variant of androgen receptor (AR), AR-V7, lacks in androgen-binding portion and leads to aggressive cancer characteristics. Reverse transcription-polymerase chain reactions (PCRs) and subsequent nested PCRs for the amplification of AR-V7 and prostate-specific antigen (PSA) transcripts were done for whole blood of patients with prostate cancer and male controls. With primary reverse transcription PCRs, AR-V7 and PSA were detected in 4.5% and 4.7% of prostate cancer, respectively. With nested PCRs, AR-V7 messenger RNA (mRNA) was positive in 43.8% of castration-sensitive prostate cancer and 48.1% of castration-resistant prostate cancer (CRPC), while PSA mRNA was positive in 6.3% of castration-sensitive prostate cancer and 18.5% of CRPC. Whole-blood samples of controls showed AR-V7 mRNA expression by nested PCR. Based on multivariate analysis, expression of AR-V7 mRNA in whole blood was not significantly correlated with clinical parameters and PSA mRNA in blood, while univariate analysis showed a correlation between AR-V7 mRNA and metastasis at initial diagnosis. Detection of AR-V7 mRNA did not predict the reduction of serum PSA in patients with CRPC following abiraterone and enzalutamide administration. In conclusion, AR-V7 mRNA expression in normal hematopoietic cells may have annihilated the manifestation of aggressiveness of prostate cancer and the prediction of the effectiveness of abiraterone and enzalutamide by the assessment of AR-V7 mRNA in blood.

  10. Bone-targeting agents in prostate cancer.

    PubMed

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

    2014-09-01

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

  11. Molecular imaging of prostate cancer with PET.

    PubMed

    Jadvar, Hossein

    2013-10-01

    Molecular imaging is paving the way for precision and personalized medicine. In view of the significant biologic and clinical heterogeneity of prostate cancer, molecular imaging is expected to play an important role in the evaluation of this prevalent disease. The natural history of prostate cancer spans from an indolent localized process to biochemical relapse after radical treatment with curative intent to a lethal castrate-resistant metastatic disease. The ongoing unraveling of the complex tumor biology of prostate cancer uniquely positions molecular imaging with PET to contribute significantly to every clinical phase of prostate cancer evaluation. The purpose of this article was to provide a concise review of the current state of affairs and potential future developments in the diagnostic utility of PET in prostate cancer.

  12. Bone-targeting agents in prostate cancer

    PubMed Central

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

    2014-01-01

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

  13. Metabolomic Imaging for Human Prostate Cancer Detection

    PubMed Central

    Wu, Chin-Lee; Jordan, Kate W.; Ratai, Eva M.; Sheng, Jinhua; Adkins, Christen B.; DeFeo, Elita M; Jenkins, Bruce G.; Ying, Leslie; McDougal, W. Scott; Cheng, Leo L.

    2010-01-01

    As current radiological approaches cannot accurately localize prostate cancer in vivo, biopsies are conducted at random within prostates for at-risk patients, leading to high false-negative rates. Metabolomic imaging can map cancer-specific biomolecular profile values onto anatomical structures to direct biopsy. In this preliminary study, we evaluated five prostatectomy-removed whole prostates from biopsy-proven cancer patients on a 7 Tesla human, whole-body magnetic resonance scanner. Localized, multi-cross-sectional, multi-voxel magnetic resonance spectra were used to construct a malignancy index based on prostate cancer metabolomic profiles obtained from previous, intact tissue analyses by a 14 Tesla spectrometer. This calculated Malignancy Index shows linear correlation with lesion size (p<0.013) and demonstrates a 93–97% overall accuracy for detecting the presence of prostate cancer lesions. PMID:20371475

  14. Effect of collagen I and fibronectin on the adhesion, elasticity and cytoskeletal organization of prostate cancer cells

    SciTech Connect

    Docheva, Denitsa; Padula, Daniela; Schieker, Matthias; Clausen-Schaumann, Hauke

    2010-11-12

    Research highlights: {yields} Depending on the metastatic origin, prostate cancer cells differ in their affinity to COL1. {yields} COL1 affects specifically the F-actin and cell elasticity of bone-derived prostate cancer cells. {yields} Cell elasticity can be used as a biomarker for cancer cells from different metastases. -- Abstract: Despite of intensive research efforts, the precise mechanism of prostate cancer metastasis in bone is still not fully understood. Several studies have suggested that specific matrix production by the bone cells, such as collagen I, supports cancer cell invasion. The aim of this study was to investigate the effect of collagen I (COL1) and fibronectin (FN) on cell adhesion, cell elasticity and cytoskeletal organization of prostate cancer cells. Two cell lines, bone marrow- (PC3) and lymph node-derived (LNCaP) were cultivated on COL1 and FN (control protein). By using a quantitative adhesion assay and time-lapse analysis, it was found that PC3, but not LNCaP, adhered strongly and were more spread on COL1. Next, PC3 and LNCaP were evaluated by atomic force microscopy (AFM) and flatness shape factor and cellular Young's modulus were calculated. The shape analysis revealed that PC3 were significantly flatter when grown on COL1 in comparison to LNCaP. In general, PC3 were also significantly stiffer than LNCaP and furthermore, their stiffness increased upon interaction with COL1. Since cell stiffness is strongly dependent on actin organization, phalloidin-based actin staining was performed and revealed that, of the two cell types as well as the two different matrix proteins, only PC3 grown on COL1 formed robust actin cytoskeleton. In conclusion, our study showed that PC3 cells have a strong affinity towards COL1. On this matrix protein, the cells adhered strongly and underwent a specific cell flattening. Moreover, with the establishment of PC3 contact to COL1 a significant increase of PC3 stiffness was observed due to a profound cytoskeletal

  15. Prostate Cancer Research Trial Helps John Spencer Treat His Cancer | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Prostate Cancer Prostate Cancer Research Trial Helps John Spencer Treat His Cancer ... because of timely detection and treatment of his prostate cancer. He participated in an NIH-sponsored clinical trial. ...

  16. Phytoestrogens selective for the estrogen receptor beta exert anti-androgenic effects in castration resistant prostate cancer.

    PubMed

    Thelen, Paul; Wuttke, Wolfgang; Seidlová-Wuttke, Dana

    2014-01-01

    Prostate cancer is the leading cause of cancer death in men of the Western world. A castration-resistant prostate cancer (CRPC) eventually will arise when a local restricted prostate carcinoma was not cured duly by radical prostatectomy or radiation therapy. Although androgen ablation therapies are considered the gold standard for treatments of advanced prostate cancer there is no curative therapy available at present. In previous pre-clinical and clinical trials several phytoestrogens were investigated for their anticancer potential in various models for prostate cancer. Phytoestrogens feature tumour preventive characteristics and most probably are involved in the low incidence rate of hormone related cancers in Asian countries. Phytoestrogens such as isoflavones can have a marked impact on the most essential therapy target of CRPC i.e. the androgen receptor. Furthermore, functional analyses solidified the notion of such drugs as androgen antagonistic. Phytoestrogens commonly feature low toxicity combined with a potential of targeted therapy. Thus, these drugs qualify for conceivable implementation in prostate cancer patients under active surveillance. In addition, relapse prevention with these drugs after radical prostatectomy or radiation therapy might be considered. This article is part of a Special Issue entitled 'Phytoestrogens'.

  17. Detection of prostate cancer with a blood-based assay for early prostate cancer antigen.

    PubMed

    Paul, Barbara; Dhir, Rajiv; Landsittel, Douglas; Hitchens, Moira R; Getzenberg, Robert H

    2005-05-15

    Prostate-specific antigen lacks specificity for prostate cancer, so the identification and characterization of a unique blood-based marker for the disease would provide for a more accurate diagnosis, reducing both unnecessary biopsies and patient uncertainty. We previously identified a novel biomarker for prostate cancer, early prostate cancer antigen (EPCA). EPCA antibodies positively stained the negative biopsies of men who, as much as 5 years later, were diagnosed with prostate cancer. The goal of this study was to determine whether EPCA antibodies could be used in a clinically applicable plasma-based immunoassay to specifically detect prostate cancer. Using an EPCA-based ELISA, the protein was measured in the plasma of 46 individuals, including prostate cancer patients, healthy individuals, other cancer patients, spinal cord injury victims, and patients with prostatitis. With a predetermined cutoff value of 1.7 absorbance at 450 nm, only the prostate cancer population, as a whole, expressed plasma-EPCA levels above the cutoff. Statistical analysis showed a significant difference in EPCA levels between the prostate cancer population and each of the other groups, specifically the healthy donors (P < 0.0001), bladder cancer patients (P = 0.03), and spinal cord injury patients (P = 0.001). Sensitivity of the EPCA assay for prostate cancer patients was 92% whereas the overall specificity was 94%. Specificity for the healthy donors was 100%. Although larger trials are required, this initial study shows the potential of EPCA to serve as a highly specific blood-based marker for prostate cancer. EPCA, when coupled with prostate-specific antigen, may help reduce the number of both unnecessary biopsies and undetected prostate tumors.

  18. PSA and beyond: alternative prostate cancer biomarkers

    PubMed Central

    2016-01-01

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

  19. IGFBP-3 is a Metastasis Suppression Gene in Prostate Cancer

    PubMed Central

    Mehta, Hemal H.; Gao, Qinglei; Galet, Colette; Paharkova, Vladislava; Wan, Junxiang; Said, Jonathan; Sohn, Joanne J.; Lawson, Gregory; Cohen, Pinchas; Cobb, Laura J.; Lee, Kuk-Wha

    2011-01-01

    The insulin-like growth factor binding protein IGFBP-3 is a pro-apoptotic and anti-angiogenic protein in prostate cancer (CaP). Epidemiological studies suggest that low IGFBP-3 is associated with greater risk of aggressive, metastatic prostate cancers, but in vivo functional data are lacking. Here we show that mice that are genetically deficient in IGFBP-3 exhibit weaker growth of primary prostate tumors growth but higher incidence of metastatic disease. Prostates in IGFBP-3 knockout mice (IGFBP-3KO mice) failed to undergo apoptosis after castration. Spontaneous prostate tumors did not develop in IGFBP-3KO mice, but splenic lymphomas occured in 23% of female IGFBP-3KO mice by 80 weeks of age. To assess the effects of IGFBP-3 deficiency on prostate cancer development, we crossed IGFBP-3KO mice with a c-Myc-driven model of CaP that develops slow-growing, non-metastatic tumors. By 24 weeks of age, well-differentiated prostate cancers were observed in all mice regardless of IGFBP-3 status. However, by 80 weeks of age IGFBP-3KO mice tended to exhibit larger prostate tumors than control mice. More strikingly, lung metastases were observed at this time in 55% of the IGFBP-3KO mice but none of the control animals. Cell lines established from Myc:IGFBP-3KO tumors displayed more aggressive phenotypes in proliferation, invasion and colony formation assays, relative to control Myc tumor cell lines. In addition, Myc:IGFBP-3KO cells exhibited evidence of epithelial-mesenchymal transition (EMT). Our findings establish a function for IGFBP-3 in suppressing metastasis in prostate cancer, and they also offer the first reported transgenic model of spontaneous metastatic prostate cancer for studies of this advanced stage of disease. PMID:21697285

  20. Emerging biomarkers of prostate cancer (Review)

    PubMed Central

    MARTIN, SARAH K.; VAUGHAN, TAYLOR B.; ATKINSON, TIMOTHY; ZHU, HAINING; KYPRIANOU, NATASHA

    2012-01-01

    Prostate cancer progression involves activation of signaling pathways controlling cell proliferation, apoptosis, anoikis, angiogenesis and metastasis. The current PSA-based test for the diagnosis of prostate cancer lacks sensitivity and specificity, resulting in missed diagnoses and unnecessary biopsies. Intense research efforts to identify serum and tissue biomarkers will expand the opportunities to understand the functional activation of cancer-related pathways and consequently lead to molecular therapeutic targeting towards inhibition of tumor growth. Current literature describes multiple biomarkers that indicate the properties of prostate cancer including its presence, stage, metastatic potential and prognosis. Used singly, assays detecting these biomarkers have their respective shortcomings. Several recent studies evaluating the clinical utilization of multiple markers show promising results in improving prostate cancer profiling. This review discusses the current understanding of biomarker signature cluster-based approaches for the diagnosis and therapeutic response of prostate cancer derived from panels of biomarker tests that provide a selective molecular signature characteristic of the tumor. As these signatures are robustly defined and their pathways are exhaustively dissected, prostate cancer can be more accurately diagnosed, characterized, staged and targeted with inhibitory antitumor agents. The growing promise surrounding the recent evidence in identifying and utilizing such biomarker panels, will lead to improvement in cancer prognosis and management of the therapeutic response of prostate cancer patients. PMID:22641253

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

    PubMed Central

    Zhang, Kaile; Zhou, Shukui; Wang, Leilei; Wang, Jianlong; Zou, Qingsong; Zhao, Weixin; Fu, Qiang; Fang, Xiaolan

    2016-01-01

    Currently there is little effective treatment available for castration resistant prostate cancer, which is responsible for the majority of prostate cancer related deaths. Emerging evidence suggested that cancer stem cells might play an important role in resistance to traditional cancer therapies, and the studies of cancer stem cells (including specific isolation and targeting on those cells) might benefit the discovery of novel treatment of prostate cancer, especially castration resistant disease. In this review, we summarized major biomarkers for prostate cancer stem cells, as well as their functional mechanisms and potential application in clinical diagnosis and treatment of patients. PMID:27447616

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

    PubMed

    Bonn, Stephanie E; Sjölander, Arvid; Tillander, Annika; Wiklund, Fredrik; Grönberg, Henrik; Bälter, Katarina

    2016-07-01

    High Body mass index (BMI) has been directly associated with risk of aggressive or fatal prostate cancer. One possible explanation may be an effect of BMI on serum levels of prostate-specific antigen (PSA). To study the association between BMI and serum PSA as well as prostate cancer risk, a large cohort of men without prostate cancer at baseline was followed prospectively for prostate cancer diagnoses until 2015. Serum PSA and BMI were assessed among 15,827 men at baseline in 2010-2012. During follow-up, 735 men were diagnosed with prostate cancer with 282 (38.4%) classified as high-grade cancers. Multivariable linear regression models and natural cubic linear regression splines were fitted for analyses of BMI and log-PSA. For risk analysis, Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) and natural cubic Cox regression splines producing standardized cancer-free probabilities were fitted. Results showed that baseline Serum PSA decreased by 1.6% (95% CI: -2.1 to -1.1) with every one unit increase in BMI. Statistically significant decreases of 3.7, 11.7 and 32.3% were seen for increasing BMI-categories of 25 < 30, 30 < 35 and ≥35 kg/m(2), respectively, compared to the reference (18.5 < 25 kg/m(2)). No statistically significant associations were seen between BMI and prostate cancer risk although results were indicative of a positive association to incidence rates of high-grade disease and an inverse association to incidence of low-grade disease. However, findings regarding risk are limited by the short follow-up time. In conclusion, BMI was inversely associated to PSA-levels. BMI should be taken into consideration when referring men to a prostate biopsy based on serum PSA-levels.

  3. Multiparametric magnetic resonance imaging of prostate cancer.

    PubMed

    Hedgire, Sandeep S; Oei, Tamara N; McDermott, Shaunagh; Cao, Kai; Patel M, Zena; Harisinghani, Mukesh G

    2012-07-01

    In India, prostate cancer has an incidence rate of 3.9 per 100,000 men and is responsible for 9% of cancer-related mortality. It is the only malignancy that is diagnosed with an apparently blind technique, i.e., transrectal sextant biopsy. With increasing numbers of high-Tesla magnetic resonance imaging (MRI) equipment being installed in India, the radiologist needs to be cognizant about endorectal MRI and multiparametric imaging for prostate cancer. In this review article, we aim to highlight the utility of multiparamteric MRI in prostate cancer. It plays a crucial role, mainly in initial staging, restaging, and post-treatment follow-up. PMID:23599562

  4. Diagnosis of prostate cancer via nanotechnological approach

    PubMed Central

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

    2015-01-01

    Prostate cancer is one of the leading causes of cancer-related deaths among the Caucasian adult males in Europe and the USA. Currently available diagnostic strategies for patients with prostate cancer are invasive and unpleasant and have poor accuracy. Many patients have been overly or underly treated resulting in a controversy regarding the reliability of current conventional diagnostic approaches. This review discusses the state-of-the-art research in the development of novel noninvasive prostate cancer diagnostics using nanotechnology coupled with suggested diagnostic strategies for their clinical implication. PMID:26527873

  5. Brassinin Combined with Capsaicin Enhances Apoptotic and Anti-metastatic Effects in PC-3 Human Prostate Cancer Cells.

    PubMed

    Kim, Sung-Moo; Oh, Eun Young; Lee, Jong Hyun; Nam, Dongwoo; Lee, Seok Geun; Lee, Junhee; Kim, Sung-Hoon; Shim, Bum Sang; Ahn, Kwang Seok

    2015-11-01

    Brassinin (BSN), a type of indole compound derived from cruciferous vegetables, has shown anti-cancer effects in cells and animals. Capsaicin (CAP), an alkaloid derived from the chilli pepper, is also of interest in for its reported efficacy against various malignancies. The objective of our study was to analyze the potential synergistic anti-tumor effects of BSN combined with CAP on prostate cancer PC-3 cells. After treatment with BSN and CAP at various concentrations, the synergistic cytotoxic effect of PC-3 cells was analyzed by MTT method, proliferation, apoptosis, mitochondrial membrane potential, colony formation, and Western blotting. Moreover, the inhibitory effects of BSN and CAP on the constitutive expressions of MMP-9/2, their enzymatic activities, cellular migration, and cell invasion were also investigated. The cytotoxicity was synergistically increased in combination compared with the single drug used; moreover, proliferation, apoptosis, mitochondrial membrane potential, and colony formation were significantly suppressed and anti-apoptotic-, proliferative-, and metastatic-related proteins were clearly abolished in the combination group. Besides, constitutive MMP-9/2 expression, their enzymatic activities, cell migration, and tumor cell invasion were inhibited, and TIMP-1 was up-regulated in the combination group in PC-3 cells. Our results indicate, for the first time, that BSN and CAP in combination exert synergistic anticancer effects in prostate carcinoma. PMID:26426257

  6. Brassinin Combined with Capsaicin Enhances Apoptotic and Anti-metastatic Effects in PC-3 Human Prostate Cancer Cells.

    PubMed

    Kim, Sung-Moo; Oh, Eun Young; Lee, Jong Hyun; Nam, Dongwoo; Lee, Seok Geun; Lee, Junhee; Kim, Sung-Hoon; Shim, Bum Sang; Ahn, Kwang Seok

    2015-11-01

    Brassinin (BSN), a type of indole compound derived from cruciferous vegetables, has shown anti-cancer effects in cells and animals. Capsaicin (CAP), an alkaloid derived from the chilli pepper, is also of interest in for its reported efficacy against various malignancies. The objective of our study was to analyze the potential synergistic anti-tumor effects of BSN combined with CAP on prostate cancer PC-3 cells. After treatment with BSN and CAP at various concentrations, the synergistic cytotoxic effect of PC-3 cells was analyzed by MTT method, proliferation, apoptosis, mitochondrial membrane potential, colony formation, and Western blotting. Moreover, the inhibitory effects of BSN and CAP on the constitutive expressions of MMP-9/2, their enzymatic activities, cellular migration, and cell invasion were also investigated. The cytotoxicity was synergistically increased in combination compared with the single drug used; moreover, proliferation, apoptosis, mitochondrial membrane potential, and colony formation were significantly suppressed and anti-apoptotic-, proliferative-, and metastatic-related proteins were clearly abolished in the combination group. Besides, constitutive MMP-9/2 expression, their enzymatic activities, cell migration, and tumor cell invasion were inhibited, and TIMP-1 was up-regulated in the combination group in PC-3 cells. Our results indicate, for the first time, that BSN and CAP in combination exert synergistic anticancer effects in prostate carcinoma.

  7. Evidence for Field Cancerization of the Prostate

    PubMed Central

    Nonn, Larisa; Ananthanarayanan, Vijayalakshmi; Gann, Peter H.

    2013-01-01

    BACKGROUND Field cancerization, which is not yet well-characterized in the prostate, occurs when large areas of an organ or tissue surface are affected by a carcinogenic insult, resulting in the development of multi-focal independent premalignant foci and molecular lesions that precede histological change. METHODS Herein, we review the cumulative body of evidence concerning field effects in the prostate and critically evaluate the methods available for the identification and validation of field effect biomarkers. Validated biomarkers for field effects have an important role to play as surrogate endpoint biomarkers in Phase II prevention trials and as clinical predictors of cancer in men with negative biopsies. RESULTS Thus far, field effects have been identified involving nuclear morphometric changes, gene expression, protein expression, gene promoter methylation, DNA damage and angiogenesis. In addition to comparing cancer-adjacent benign tissue to more distant areas or to “supernormal” tissue from cancer-free organs, investigators can use a nested case–control design for negative biopsies that offers a number of unique advantages. CONCLUSIONS True carcinogenic field effects should be distinguished from secondary responses of the microenvironment to a developing tumor, although the latter may still lead to useful clinical prediction tools. PMID:19462462

  8. Epigenetic modulators as therapeutic targets in prostate cancer.

    PubMed

    Graça, Inês; Pereira-Silva, Eva; Henrique, Rui; Packham, Graham; Crabb, Simon J; Jerónimo, Carmen

    2016-01-01

    Prostate cancer is one of the most common non-cutaneous malignancies among men worldwide. Epigenetic aberrations, including changes in DNA methylation patterns and/or histone modifications, are key drivers of prostate carcinogenesis. These epigenetic defects might be due to deregulated function and/or expression of the epigenetic machinery, affecting the expression of several important genes. Remarkably, epigenetic modifications are reversible and numerous compounds that target the epigenetic enzymes and regulatory proteins were reported to be effective in cancer growth control. In fact, some of these drugs are already being tested in clinical trials. This review discusses the most important epigenetic alterations in prostate cancer, highlighting the role of epigenetic modulating compounds in pre-clinical and clinical trials as potential therapeutic agents for prostate cancer management. PMID:27651838

  9. ETS fusion genes in prostate cancer.

    PubMed

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

    2014-06-01

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

  10. Obesity promotes aerobic glycolysis in prostate cancer cells.

    PubMed

    Cavazos, David A; deGraffenried, Matthew J; Apte, Shruti A; Bowers, Laura W; Whelan, Kaitlin A; deGraffenried, Linda A

    2014-01-01

    Obesity is the leading preventable comorbidity associated with increased prostate cancer-related recurrence and mortality. Epidemiological and clinical studies indicate that a body mass index >30 is associated with increased oxidative DNA damage within the prostate gland and increased prostate cancer-related mortality. Here we provide evidence that obesity promotes worse clinical outcome through induction of metabolic abnormalities known to promote genotoxic stress. We have previously reported that blood serum derived from obese mice may enhance the proliferative and invasive potential of human prostate cancer cell lines ex vivo. Here we show that a 1-h exposure of LNCaP or PacMetUT1 prostate cancer cell lines and nonmalignant RWPE-1 prostate epithelial cells to 2% serum from obese mice induces markers of aerobic glycolysis relative to those exposed to serum from nonobese mice. This metabolic change was correlated with accumulation of reactive oxygen species (ROS) and increased frequency of DNA double-strand breaks. Interestingly, N-tert-Butylhydroxylamine, an antioxidant, significantly suppressed markers of aerobic glycolysis in the cells exposed to the blood serum of obese mice, suggesting that ROS contributes to a metabolic shift toward aerobic glycolysis. Here we describe obesity-induced changes in key metabolic markers that impact prostate cancer cell progression and explore the role of antioxidants in ameliorating these effects. PMID:25264717

  11. The association between metabolic syndrome and the risk of prostate cancer, high-grade prostate cancer, advanced prostate cancer, prostate cancer-specific mortality and biochemical recurrence

    PubMed Central

    2013-01-01

    Background Although a previous meta-analysis reported no association between metabolic syndrome (MetS) and prostate cancer risk, a number of studies suggest that MetS may be associated with the aggressiveness and progression of prostate cancer. However, these results have been inconsistent. This systematic review and meta-analysis investigated the nature of this association. Methods We systematically searched MEDLINE, EMBASE and bibliographies of retrieved studies up to January 2013 using the keywords “metabolic syndrome” and “prostate cancer”. We assessed relative risks (RRs) of the prostate cancer, several parameters of prostate cancer aggressiveness and progression associated with MetS using 95% confidence intervals (95% CIs). Results The literature search produced 547 hits from which 19 papers were extracted for the meta-analysis. In cancer-free population with and without MetS, the combined adjusted RR (95% CI) of prostate cancer risk and prostate cancer-specific mortality in longitudinal cohort studies is 0.96 (0.85 ~ 1.09) and 1.12 (1.02 ~ 1.23) respectively. In the prostate cancer patients with and without MetS, the combined unadjusted OR (95% CI) of high grade Gleason prostate cancer is 1.44 (1.20 ~ 1.72), the OR of advanced prostate cancer is 1.37 (1.12 ~ 1.68) and the OR of biochemical recurrence is 2.06 (1.43 ~ 2.96). Conclusions The overall analyses revealed no association between MetS and prostate cancer risk, although men with MetS appear more likely to have high-grade prostate cancer and more advanced disease, were at greater risk of progression after radical prostatectomy and were more likely to suffer prostate cancer-specific death. Further primary studies with adjustment for appropriate confounders and larger, prospective, multicenter investigations are required. PMID:23406686

  12. New developments in metastatic prostate cancer therapy.

    PubMed

    Manickavasagar, Thubeena; Gilson, Clare; Chowdhury, Simon; Kirby, Roger

    2015-04-01

    Metastatic prostate cancer is still commonly a lethal condition. The concept that 'men with prostate cancer die with rather than of their cancer' has been shown to be false. It is estimated that 10-20% of men in the UK present with locally advanced disease. Median overall survival remains only 3.5 years for men presenting with metastatic disease. The use of LHRH analogues to achieve medical castration has become the gold standard for both locally advanced prostate cancer, combined with radiotherapy, and metastatic disease. Androgen deprivation therapy (ADT) is the standard first-line treatment for advanced disease resulting in improvements in symptoms, radiological findings and PSA levels. Ultimately the majority of men with advanced prostate cancer will develop resistance to ADT Docetaxel is the standard first-line therapy recommended by international guidelines for patients with symptomatic metastatic castrate refractory prostate cancer who are suitable candidates for chemotherapy. More than 90% of patients with castrate refractory prostate cancer have bone metastases. Radium-223 dichloride is a novel alpha-emitting radiopharmaceutical agent, which mimics calcium and therefore targets bone metastases. It is indicated in patients with metastatic castrate refractory prostate cancer who have symptomatic bone metastases without visceral metastases.

  13. Prostate Cancer and Bone: The Elective Affinities

    PubMed Central

    2014-01-01

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

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

    PubMed

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

    2013-10-01

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

  15. Differential metabolism of dehydroepiandrosterone sulfate and estrogen conjugates by normal or malignant AXC/SSh rat prostate cells and effects of these steroid conjugates on cancer cell proliferation in vitro.

    PubMed

    Huot, R I; Shain, S A

    1988-06-01

    Normal AXC/SSh rat ventral prostate and clonally derived AXC/SSh rat prostate cancer cells were evaluated for ability to metabolize estrone sulfate (E1S), estrone glucuronide (E1G), or dehydroepiandrosterone sulfate (DHEAS). Both normal and malignant prostate cells converted E1S to estrone. Neither normal nor malignant prostate cells had significant ability to metabolize DHEAS to DHEA, indicating differential specificity of prostate sulfatases(s) for estrogen and androgen sulfates. Both normal and neoplastic prostate cells possess beta-glucuronidase which hydrolyzed E1G to estrone. To assess potential physiologic consequences of these enzymatic activities, we determined the effect of steroid conjugates on in vitro proliferation of selected clonal lines of AXC/SSh rat prostate cancer cells. DHEAS, 10(-6) to 10(-9) M in decade intervals, did not affect in vitro proliferation of AXC/SSh prostate cancer cells; however, 10(-5) M DHEAS decreased in vitro proliferation of these cells. Neither E1S nor E1G, 10(-5) to 10(-9) M in decade intervals, affected in vitro proliferation of AXC/SSh prostate cancer cells. These findings suggest that low residual levels of steroid conjugates, which are not removed by charcoal stripping of serum, do not affect demonstrated in vitro androgen modulation of AXC/SSh rat prostate cancer cell proliferation (Cancer Res. 46, 3775-3781, 1986).

  16. Effects of recreational soccer in men with prostate cancer undergoing androgen deprivation therapy: study protocol for the ‘FC Prostate’ randomized controlled trial

    PubMed Central

    2013-01-01

    Background Androgen deprivation therapy (ADT) is a cornerstone in the treatment of advanced prostate cancer. Adverse musculoskeletal and cardiovascular effects of ADT are widely reported and investigations into the potential of exercise to ameliorate the effects of treatment are warranted. The ‘Football Club (FC) Prostate’ study is a randomized trial comparing the effects of soccer training with standard treatment approaches on body composition, cardiovascular function, physical function parameters, glucose tolerance, bone health, and patient-reported outcomes in men undergoing ADT for prostate cancer. Methods/Design Using a single-center randomized controlled design, 80 men with histologically confirmed locally advanced or disseminated prostate cancer undergoing ADT for 6 months or more at The Copenhagen University Hospital will be enrolled on this trial. After baseline assessments eligible participants will be randomly assigned to a soccer training group or a control group receiving usual care. The soccer intervention will consist of 12 weeks of training 2–3 times/week for 45–60 min after which the assessment protocol will be repeated. Soccer training will then continue bi-weekly for an additional 20 weeks at the end of which all measures will be repeated to allow for additional analyses of long-term effects. The primary endpoint is changes in lean body mass from baseline to 12 weeks assessed by dual X-ray absorptiometry scan. Secondary endpoints include changes of cardiovascular, metabolic, and physical function parameters, as well as markers of bone metabolism and patient-reported outcomes. Discussion The FC Prostate trial will assess the safety and efficacy of a novel soccer-training approach to cancer rehabilitation on a number of clinically important health outcomes in men with advanced prostate cancer during ADT. The results may pave the way for innovative, community-based interventions in the approach to treating prostate cancer. Trial

  17. Trichomonas vaginalis: a possible foe to prostate cancer.

    PubMed

    Zhu, Ziwen; Davidson, Kristoffer T; Brittingham, Andrew; Wakefield, Mark R; Bai, Qian; Xiao, Huaping; Fang, Yujiang

    2016-10-01

    Prostate cancer (PCA) is the most common malignancy in men in USA, and the role of Trichomonas vaginalis (T. vag) in the development of PCA is still controversial. Clonogenic assay, PCNA staining, TUNEL staining and caspase-3 activity assay were used to investigate the in vitro role of T. vag in human prostate cancer. We further investigated the possible molecular mechanisms using RT-PCR and immunohistochemical staining. Culture supernatant of T. vag inhibits growth of PC-3 prostate cancer cells, and this correlated with upregulation of p21. Culture supernatant of T. vag induced apoptosis of PC-3 cells, and this correlated with downregulation of Bcl-2. The growth inhibition effect of culture supernatant of T. vag is also demonstrated in another prostate cancer cell line DU145, suggesting that its effect is not specific to one prostate cancer cell line. Culture supernatant of T. vag inhibits growth of prostate cancer by inhibition of proliferation and promotion of apoptosis. Such a study might be helpful to address the association between PCA and infection of T. vag. PMID:27613161

  18. ESTIMATING PERSON-CENTERED TREATMENT (PeT) EFFECTS USING INSTRUMENTAL VARIABLES: AN APPLICATION TO EVALUATING PROSTATE CANCER TREATMENTS

    PubMed Central

    BASU, ANIRBAN

    2014-01-01

    SUMMARY This paper builds on the methods of local instrumental variables developed by Heckman and Vytlacil (1999, 2001, 2005) to estimate person-centered treatment (PeT) effects that are conditioned on the person’s observed characteristics and averaged over the potential conditional distribution of unobserved characteristics that lead them to their observed treatment choices. PeT effects are more individualized than conditional treatment effects from a randomized setting with the same observed characteristics. PeT effects can be easily aggregated to construct any of the mean treatment effect parameters and, more importantly, are well suited to comprehend individual-level treatment effect heterogeneity. The paper presents the theory behind PeT effects, and applies it to study the variation in individual-level comparative effects of prostate cancer treatments on overall survival and costs. PMID:25620844

  19. Triple orbital metastases from prostate cancer.

    PubMed

    Tun, Kagan; Bulut, Turgay

    2016-01-01

    Prostate carcinoma, when metastatic, typically involves bone and produces both osteoblastic and osteolytic changes. A 73-year-old man was admitted to our department because of unilateral progressive proptosis and visual blurriness for 3 months. The patient had a history of prostate adenocarcinoma diagnosis 5 years ago. We report a case of orbital involvement presented that intraorbital mass (including periocular structures), temporal bone and temporal muscle from prostate cancer. The mass was removed with total excision. Despite the frequency of bone metastasis in prostatic carcinoma, triple orbital metastases are extremely rare. The best of our knowledge, prostate adenocarcinoma and its triple (temporal bone, temporal muscle and intraorbital mass) orbital metastases have not been published previously. Metastatic orbital tumor secondary to prostate cancer should be considered in patients who have varying degrees of eye symptoms. PMID:27591068

  20. Marital Satisfaction of Advanced Prostate Cancer Survivors and Their Spousal Caregivers: The Dyadic Effects of Physical and Mental Health

    PubMed Central

    Zhou, Eric S.; Kim, Youngmee; Rasheed, Mikal; Benedict, Catherine; Bustillo, Natalie E.; Soloway, Mark; Kava, Bruce R.; Penedo, Frank J.

    2010-01-01

    Objective Coping with the physical and mental side effects of diagnosis and treatment for advanced prostate cancer (APC) is a challenge for both survivors and their spousal caregivers. There is a gap in our current understanding of the dyadic adjustment process on marital satisfaction in this population. The current study sought to: 1) document levels of physical and mental health, and marital satisfaction and 2) evaluate the relationship between physical and mental health with marital satisfaction in this understudied population. Methods APC survivors who had undergone hormonal therapy within the past year and their spousal caregiver participated in the study (N=29 dyads). Physical and mental health was assessed using the MOS SF-36 Health Survey and marital satisfaction was evaluated using the Dyadic Adjustment Scale. Results The Actor-Partner Interdependence Model revealed strong relations between physical and mental health with marital satisfaction for both survivor and caregiver (actor effects). Furthermore, caregiver physical and mental health was related with the survivor's marital satisfaction (partner effect). Conclusions Levels of mental health and marital satisfaction were comparable to community-based or prostate cancer samples, while physical health was higher. Marital satisfaction between APC survivors and their spousal caregivers may be influenced by both physical and mental health functioning. In particular, APC survivor functioning may affect both his marital satisfaction as well as his spousal caregiver's. This has implications for psychosocial interventions for APC dyads. Further evaluation of the complex nature of survivor/caregiver dyadic adjustment in dealing with APC is necessary. PMID:20925137

  1. Prostate MRI can reduce overdiagnosis and overtreatment of prostate cancer.

    PubMed

    Rosenkrantz, Andrew B; Taneja, Samir S

    2015-08-01

    The contemporary management of prostate cancer (PCa) has been criticized as fostering overdetection and overtreatment of indolent disease. In particular, the historical inability to identify those men with an elevated PSA who truly warrant biopsy, and, for those needing biopsy, to localize aggressive tumors within the prostate, has contributed to suboptimal diagnosis and treatment strategies. This article describes how modern multi-parametric MRI of the prostate addresses such challenges and reduces both overdiagnosis and overtreatment. The central role of diffusion-weighted imaging (DWI) in contributing to MRI's current impact is described. Prostate MRI incorporating DWI achieves higher sensitivity than standard systematic biopsy for intermediate-to-high risk tumor, while having lower sensitivity for low-grade tumors that are unlikely to impact longevity. Particular applications of prostate MRI that are explored include selection of a subset of men with clinical suspicion of PCa to undergo biopsy as well as reliable confirmation of only low-risk disease in active surveillance patients. Various challenges to redefining the standard of care to incorporate solely MRI-targeted cores, without concomitant standard systematic cores, are identified. These include needs for further technical optimization of current systems for performing MRI-targeted biopsies, enhanced education and expertise in prostate MRI among radiologists, greater standardization in prostate MRI reporting across centers, and recognition of the roles of pre-biopsy MRI and MRI-targeted biopsy by payers. Ultimately, it is hoped that the medical community in the United States will embrace prostate MRI and MRI-targeted biopsy, allowing all patients with known or suspected prostate cancer to benefit from this approach.

  2. A Perspective of Immunotherapy for Prostate Cancer

    PubMed Central

    Silvestri, Ida; Cattarino, Susanna; Giantulli, Sabrina; Nazzari, Cristina; Collalti, Giulia; Sciarra, Alessandro

    2016-01-01

    In cancer patients, the immune system is often altered with an excess of inhibitory factors, such as immunosuppressive cytokines, produced by regulatory T cells (Treg) or myeloid-derived suppressor cells (MDSC). The manipulation of the immune system has emerged as one of new promising therapies for cancer treatment, and also represents an attractive strategy to control prostate cancer (PCa). Therapeutic cancer vaccines and immune checkpoint inhibitors have been the most investigated in clinical trials. Many trials are ongoing to define the effects of immune therapy with established treatments: androgen deprivation therapy (ADT) and chemotherapy (CT) or radiotherapy (RT). This article discusses some of these approaches in the context of future treatments for PCa. PMID:27399780

  3. Association of serum EPCA-2 level with prostate cancer in Chinese Han population

    PubMed Central

    Wang, Lei; Ma, Ling; Wang, Xinli; Li, Bing; Guo, Shan; Qiao, Qingdong

    2015-01-01

    Background: Early prostate cancer antigen 2 (EPCA-2), a kind of nuclear matrix protein, may relate to prostate cancer. However, the association of EPCA-2 level in serum with prostate diseases has not been clarified in Chinese Han population. Methods: EPCA-2 and prostate-specific antigen (PSA) levels in serum were detected by enzyme linked immunosorbent assay in 116 patients with prostate cancer (PCa), 342 patients with benign prostatic hyperplasia (BPH), and 174 healthy controls (Control) in Chinese population. Associations of serum EPCA-2 and PSA level with prostate diseases were analyzed by ANOVA. Comparison of diagnostic effect for prostate cancer between EPCA-2 and PSA was evaluated by Receiver Operator Curve, Chi-square test, and others. Results: Serum EPCA-2 and PSA levels in PCa group were significantly higher than BPH and Control group (EPCA-2: F=200.05, P<0.01; PSA: F=210.65, P<0.01). However, EPCA-2 levels in the prostate cancers with different pathological grade were no significant difference. Furthermore, for detection of prostate cancer, EPCA-2 had a sensitivity of 81.9% and a specificity of 87.6%. Conclusions: Serum EPCA-2 could be used as a potential serological marker to diagnose prostate cancer in Chinese Han population, which was more specific than PSA and did not associate with pathological grades of prostate cancer. PMID:26464694

  4. Evolving Recommendations on Prostate Cancer Screening.

    PubMed

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

    2016-01-01

    Results of a number of studies demonstrate that the serum prostate-specific antigen (PSA) in and of itself is an inadequate screening test. Today, one of the most pressing questions in prostate cancer medicine is how can screening be honed to identify those who have life-threatening disease and need aggressive treatment. A number of efforts are underway. One such effort is the assessment of men in the landmark Prostate Cancer Prevention Trial that has led to a prostate cancer risk calculator (PCPTRC), which is available online. PCPTRC version 2.0 predicts the probability of the diagnosis of no cancer, low-grade cancer, or high-grade cancer when variables such as PSA, age, race, family history, and physical findings are input. Modern biomarker development promises to provide tests with fewer false positives and improved ability to find high-grade cancers. Stockholm III (STHLM3) is a prospective, population-based, paired, screen-positive, prostate cancer diagnostic study assessing a combination of plasma protein biomarkers along with age, family history, previous biopsy, and prostate examination for prediction of prostate cancer. Multiparametric MRI incorporates anatomic and functional imaging to better characterize and predict future behavior of tumors within the prostate. After diagnosis of cancer, several genomic tests promise to better distinguish the cancers that need treatment versus those that need observation. Although the new technologies are promising, there is an urgent need for evaluation of these new tests in high-quality, large population-based studies. Until these technologies are proven, most professional organizations have evolved to a recommendation of informed or shared decision making in which there is a discussion between the doctor and patient. PMID:27249774

  5. Potent inhibitory effect of δ-tocopherol on prostate cancer cells cultured in vitro and grown as xenograft tumors in vivo.

    PubMed

    Huang, Huarong; He, Yan; Cui, Xiao-Xing; Goodin, Susan; Wang, Hong; Du, Zhi Yun; Li, Dongli; Zhang, Kun; Tony Kong, Ah-Ng; DiPaola, Robert S; Yang, Chung S; Conney, Allan H; Zheng, Xi

    2014-11-01

    In the present study, the effects of δ-tocopherol (δ-T) on growth and apoptosis of human prostate cancer cells were determined and compared with that of α-tocopherol (α-T), a commonly used form of vitamin E. Treatment of human prostate cancer cells with δ-T resulted in strong growth inhibition and apoptosis stimulation, while the effects of α-T were modest. The strong effects of δ-T on the cells were associated with suppression of androgen receptor (AR) activity and decreased level of prostate specific antigen (PSA) that is a downstream target of the AR signaling. In the in vivo study, we found that δ-T had a more potent inhibitory effect on the formation and growth of prostate xenograft tumors than that of α-T. Moreover, δ-T inhibited proliferation and stimulated apoptosis in the tumors. The present study identified δ-T as a better form of vitamin E than α-T for future clinical studies of prostate cancer prevention.

  6. The protective effect of soybean phytochemicals on androgen responsive human prostate cancer cells LNCaP is likely mediated through modulation of hormone/cytokine-dependent pathways

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Population studies suggested that the consumption of a soy rich diet provides protective effects against several chronic diseases including prostate cancer. However, the active components in soy, as well as the mechanisms of action of soy’s protective effects, remain unclear. It would be important t...

  7. Cold Atmospheric Plasma Treatment Induces Anti-Proliferative Effects in Prostate Cancer Cells by Redox and Apoptotic Signaling Pathways.

    PubMed

    Weiss, Martin; Gümbel, Denis; Hanschmann, Eva-Maria; Mandelkow, Robert; Gelbrich, Nadine; Zimmermann, Uwe; Walther, Reinhard; Ekkernkamp, Axel; Sckell, Axel; Kramer, Axel; Burchardt, Martin; Lillig, Christopher H; Stope, Matthias B

    2015-01-01

    One of the promising possibilities of the clinical application of cold plasma, so-called cold atmospheric plasma (CAP), is its application on malignant cells and cancer tissue using its anti-neoplastic effects, primarily through the delivery of reactive oxygen and nitrogen species (ROS, RNS). In this study, we investigated the impact of CAP on cellular proliferation and consecutive molecular response mechanisms in established prostate cancer (PC) cell lines. PC cells showed a significantly reduced cell growth following CAP treatment as a result of both an immediate increase of intracellular peroxide levels and through the induction of apoptosis indicated by annexin V assay, TUNEL assay, and the evaluation of changes in nuclear morphology. Notably, co-administration of N-acetylcysteine (NAC) completely neutralized CAP effects by NAC uptake and rapid conversion to glutathione (GSH). Vitamin C could not counteract the CAP induced effects on cell growth. In summary, relatively short treatments with CAP of 10 seconds were sufficient to induce a significant inhibition of cancer proliferation, as observed for the first time in urogenital cancer. Therefore, it is important to understand the mode of CAP related cell death and clarify and optimize CAP as cancer therapy. Increased levels of peroxides can alter redox-regulated signaling pathways and can lead to growth arrest and apoptosis. We assume that the general intracellular redox homeostasis, especially the levels of cellular GSH and peroxidases such as peroxiredoxins affect the outcome of the CAP treatment. PMID:26132846

  8. Cold Atmospheric Plasma Treatment Induces Anti-Proliferative Effects in Prostate Cancer Cells by Redox and Apoptotic Signaling Pathways.

    PubMed

    Weiss, Martin; Gümbel, Denis; Hanschmann, Eva-Maria; Mandelkow, Robert; Gelbrich, Nadine; Zimmermann, Uwe; Walther, Reinhard; Ekkernkamp, Axel; Sckell, Axel; Kramer, Axel; Burchardt, Martin; Lillig, Christopher H; Stope, Matthias B

    2015-01-01

    One of the promising possibilities of the clinical application of cold plasma, so-called cold atmospheric plasma (CAP), is its application on malignant cells and cancer tissue using its anti-neoplastic effects, primarily through the delivery of reactive oxygen and nitrogen species (ROS, RNS). In this study, we investigated the impact of CAP on cellular proliferation and consecutive molecular response mechanisms in established prostate cancer (PC) cell lines. PC cells showed a significantly reduced cell growth following CAP treatment as a result of both an immediate increase of intracellular peroxide levels and through the induction of apoptosis indicated by annexin V assay, TUNEL assay, and the evaluation of changes in nuclear morphology. Notably, co-administration of N-acetylcysteine (NAC) completely neutralized CAP effects by NAC uptake and rapid conversion to glutathione (GSH). Vitamin C could not counteract the CAP induced effects on cell growth. In summary, relatively short treatments with CAP of 10 seconds were sufficient to induce a significant inhibition of cancer proliferation, as observed for the first time in urogenital cancer. Therefore, it is important to understand the mode of CAP related cell death and clarify and optimize CAP as cancer therapy. Increased levels of peroxides can alter redox-regulated signaling pathways and can lead to growth arrest and apoptosis. We assume that the general intracellular redox homeostasis, especially the levels of cellular GSH and peroxidases such as peroxiredoxins affect the outcome of the CAP treatment.

  9. Co-targeting EGFR and survivin with a bivalent aptamer-dual siRNA chimera effectively suppresses prostate cancer.

    PubMed

    Liu, Hong Yan; Yu, Xiaolin; Liu, Haitao; Wu, Daqing; She, Jin-Xiong

    2016-01-01

    Current targeted therapies using small kinase inhibitors and antibodies have limited efficacy in treating prostate cancer (PCa), a leading cause of cancer death in American men. We have developed a novel strategy by engineering an RNA-based aptamer-siRNA chimera, in which a bivalent aptamer specifically binds prostate-specific membrane antigen (PSMA) via an antibody-like structure to promote siRNA internalization in PCa cells, and two siRNAs specific to EGFR and survivin are fused between two aptamers. The chimera is able to inhibit EGFR and survivin simultaneously and induce apoptosis effectively in vitro and in vivo. In the C4-2 PCa xenograft model, the treatment with the chimera significantly suppresses tumor growth and angiogenesis. The inhibition of angiogenesis is mediated by an EGFR-HIF1α-VEGF-dependent mechanism. Our results support that the bivalent aptamer-driven delivery of two siRNAs could be a new combination therapeutic strategy to effectively inhibit multiple and conventionally "undruggable" targets. PMID:27456457

  10. Co-targeting EGFR and survivin with a bivalent aptamer-dual siRNA chimera effectively suppresses prostate cancer

    PubMed Central

    Liu, Hong Yan; Yu, Xiaolin; Liu, Haitao; Wu, Daqing; She, Jin-Xiong

    2016-01-01

    Current targeted therapies using small kinase inhibitors and antibodies have limited efficacy in treating prostate cancer (PCa), a leading cause of cancer death in American men. We have developed a novel strategy by engineering an RNA-based aptamer-siRNA chimera, in which a bivalent aptamer specifically binds prostate-specific membrane antigen (PSMA) via an antibody-like structure to promote siRNA internalization in PCa cells, and two siRNAs specific to EGFR and survivin are fused between two aptamers. The chimera is able to inhibit EGFR and survivin simultaneously and induce apoptosis effectively in vitro and in vivo. In the C4-2 PCa xenograft model, the treatment with the chimera significantly suppresses tumor growth and angiogenesis. The inhibition of angiogenesis is mediated by an EGFR-HIF1α-VEGF-dependent mechanism. Our results support that the bivalent aptamer-driven delivery of two siRNAs could be a new combination therapeutic strategy to effectively inhibit multiple and conventionally “undruggable” targets. PMID:27456457

  11. Co-targeting EGFR and survivin with a bivalent aptamer-dual siRNA chimera effectively suppresses prostate cancer.

    PubMed

    Liu, Hong Yan; Yu, Xiaolin; Liu, Haitao; Wu, Daqing; She, Jin-Xiong

    2016-07-26

    Current targeted therapies using small kinase inhibitors and antibodies have limited efficacy in treating prostate cancer (PCa), a leading cause of cancer death in American men. We have developed a novel strategy by engineering an RNA-based aptamer-siRNA chimera, in which a bivalent aptamer specifically binds prostate-specific membrane antigen (PSMA) via an antibody-like structure to promote siRNA internalization in PCa cells, and two siRNAs specific to EGFR and survivin are fused between two aptamers. The chimera is able to inhibit EGFR and survivin simultaneously and induce apoptosis effectively in vitro and in vivo. In the C4-2 PCa xenograft model, the treatment with the chimera significantly suppresses tumor growth and angiogenesis. The inhibition of angiogenesis is mediated by an EGFR-HIF1α-VEGF-dependent mechanism. Our results support that the bivalent aptamer-driven delivery of two siRNAs could be a new combination therapeutic strategy to effectively inhibit multiple and conventionally "undruggable" targets.

  12. Novel diagnostic biomarkers for prostate cancer

    PubMed Central

    Madu, Chikezie O.; Lu, Yi

    2010-01-01

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

  13. Lymph node staging in prostate cancer.

    PubMed

    Sankineni, Sandeep; Brown, Anna M; Fascelli, Michele; Law, Yan Mee; Pinto, Peter A; Choyke, Peter L; Turkbey, Baris

    2015-05-01

    Nodal staging is important in prostate cancer treatment. While surgical lymph node dissection is the classic method of determining whether lymph nodes harbor malignancy, this is a very invasive technique. Current noninvasive approaches to identifying malignant lymph nodes are limited. Conventional imaging methods rely on size and morphology of lymph nodes and have notoriously low sensitivity for detecting malignant nodes. New imaging techniques such as targeted positron emission tomography (PET) imaging and magnetic resonance lymphography (MRL) with iron oxide particles are promising for nodal staging of prostate cancer. In this review, the strengths and limitations of imaging techniques for lymph node staging of prostate cancer are discussed.

  14. Novel diagnostic biomarkers for prostate cancer.

    PubMed

    Madu, Chikezie O; Lu, Yi

    2010-10-06

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

  15. Occupation and prostate cancer risk in Sweden.

    PubMed

    Sharma-Wagner, S; Chokkalingam, A P; Malker, H S; Stone, B J; McLaughlin, J K; Hsing, A W

    2000-05-01

    To provide new leads regarding occupational prostate cancer risk factors, we linked 36,269 prostate cancer cases reported to the Swedish National Cancer Registry during 1961 to 1979 with employment information from the 1960 National Census. Standardized incidence ratios for prostate cancer, within major (1-digit), general (2-digit), and specific (3-digit) industries and occupations, were calculated. Significant excess risks were seen for agriculture-related industries, soap and perfume manufacture, and leather processing industries. Significantly elevated standardized incidence ratios were also seen for the following occupations: farmers, leather workers, and white-collar occupations. Our results suggest that farmers; certain occupations and industries with exposures to cadmium, herbicides, and fertilizers; and men with low occupational physical activity levels have elevated prostate cancer risks. Further research is needed to confirm these findings and identify specific exposures related to excess risk in these occupations and industries.

  16. Newer potential biomarkers in prostate cancer.

    PubMed

    Wright, Jonathan L; Lange, Paul H

    2007-01-01

    Prostate-specific antigen (PSA) screening has led to a significant rise in the number of men diagnosed with prostate cancer and an associated increase in biopsies performed. Despite its limitations, including a positive predictive value of only 25%-40%, PSA remains the only generally accepted biomarker for prostate cancer. There is a need for better tools to not only identify men with prostate cancer, but also to recognize those with potentially lethal disease who will benefit from intervention. A great deal of work has been done worldwide to improve our knowledge of the genetics behind prostate cancer and the specificity of PSA by developing assays for different PSA isoforms. Common genetic alterations in prostate cancer patients have been identified, including CpG hypermethylation of GSPT1 and TMPRSS2:ERG gene fusion. Serum and urine detection of RNA biomarkers (eg, PCA3) and prostate cancer tissue protein antibodies (eg, EPCA) are being evaluated for detection and prognostic tools. This article reviews some of the promising developments in biomarkers.

  17. Newer Potential Biomarkers in Prostate Cancer

    PubMed Central

    Wright, Jonathan L; Lange, Paul H

    2007-01-01

    Prostate-specific antigen (PSA) screening has led to a significant rise in the number of men diagnosed with prostate cancer and an associated increase in biopsies performed. Despite its limitations, including a positive predictive value of only 25%–40%, PSA remains the only generally accepted biomarker for prostate cancer. There is a need for better tools to not only identify men with prostate cancer, but also to recognize those with potentially lethal disease who will benefit from intervention. A great deal of work has been done worldwide to improve our knowledge of the genetics behind prostate cancer and the specificity of PSA by developing assays for different PSA isoforms. Common genetic alterations in prostate cancer patients have been identified, including CpG hypermethylation of GSPT1 and TMPRSS2:ERG gene fusion. Serum and urine detection of RNA biomarkers (eg, PCA3) and prostate cancer tissue protein antibodies (eg, EPCA) are being evaluated for detection and prognostic tools. This article reviews some of the promising developments in biomarkers. PMID:18231617

  18. Evaluating localized prostate cancer and identifying candidates for focal therapy.

    PubMed

    Sartor, A Oliver; Hricak, Hedvig; Wheeler, Thomas M; Coleman, Jonathan; Penson, David F; Carroll, Peter R; Rubin, Mark A; Scardino, Peter T

    2008-12-01

    Can focal therapy successfully control prostate cancer? Also, if so, which patients should be considered eligible? With limited data available from relatively few patients, these questions are difficult to answer. At this writing, the most likely candidates for focal therapy are patients with low-risk, small-volume tumors, located in 1 region or sector of the prostate, who would benefit from early intervention. The difficulty lies in reliably identifying these men. The larger number of cores obtained in each needle biopsy session has increased both the detection of prostate cancer and the potential risk of overtreating many patients whose cancers pose very little risk to life or health. Urologists typically perform at least a 12-core template biopsy. Although the debate continues about the optimal template, laterally and peripherally directed biopsies have been shown to improve the diagnostic yield. However, as many as 25% of tumors arise anteriorly and can be missed with peripherally directed techniques. Prostate cancer tends to be multifocal, even in its earliest stages. However, the secondary cancers are usually smaller and less aggressive than the index cancer. They appear similar to the incidental cancers found in cystoprostatectomy specimens and appear to have little effect on prognosis in surgical series. When a single focus of cancer is found in 1 core, physicians rightly suspect that more foci of cancer are present in the prostate. Assessing the risk in these patients is challenging when determined by the biopsy data alone. To predict the presence of a very low-risk or "indolent" cancer, nomograms have been developed to incorporate clinical stage, Gleason grade, prostate-specific antigen levels, and prostate volume, along with the quantitative analysis of the biopsy results. Transperineal "mapping" or "saturation" biopsies have been advocated to detect cancers missed or underestimated by previous transrectal biopsies. This approach could provide the

  19. Polyphenols: Key Issues Involved in Chemoprevention of Prostate Cancer

    PubMed Central

    Cimino, Sebastiano; Sortino, Giuseppe; Favilla, Vincenzo; Castelli, Tommaso; Madonia, Massimo; Sansalone, Salvatore; Russo, Giorgio Ivan; Morgia, Giuseppe

    2012-01-01

    Prostate cancer is is the most common solid neoplasm and it is now recognized as one of the most important medical problems facing the male population. Due to its long latency and its identifiable preneoplastic lesions, prostate cancer is an ideal target tumor for chemoprevention. Different compounds are available and certainly polyphenols represent those with efficacy against prostate cancer. This review take a look at activity and properties of major polyphenolic substances, such as epigallocatechin-3-gallate, curcumin, resveratrol and the flavonoids quercetin and genistein. Although the current studies are limited, mechanisms of action of polyphenols added with the lack of side effects show a a start for future strategies in prostate chemoprevention. PMID:22690272

  20. Estimation of effective imaging dose for kilovoltage intratreatment monitoring of the prostate position during cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Ng, J. A.; Booth, J.; Poulsen, P.; Kuncic, Z.; Keall, P. J.

    2013-09-01

    Kilovoltage intratreatment monitoring (KIM) is a novel real-time localization modality where the tumor position is continuously measured during intensity modulated radiation therapy (IMRT) or intensity modulated arc therapy (IMAT) by a kilovoltage (kV) x-ray imager. Adding kV imaging during therapy adds radiation dose. The additional effective dose is quantified for prostate radiotherapy and compared to dose from other localization modalities. The software PCXMC 2.0 was used to calculate the effective dose delivered to a phantom as a function of imager angle and field size for a Varian On-Board Imager. The average angular effective dose was calculated for a field size of 6 cm × 6 cm. The average angular effective dose was used in calculations for different treatment scenarios. Treatment scenarios considered were treatment type and fractionation. For all treatment scenarios, (i.e. conventionally fractionated and stereotactic body radiotherapy (SBRT), IMRT and IMAT), the total KIM dose at 1 Hz ranged from 2-10 mSv. This imaging dose is less than the Navotek radioactive implant dose (64 mSv) and a standard SBRT cone beam computed tomography pretreatment scan dose (22 mSv) over an entire treatment regime. KIM delivers an acceptably low effective dose for daily use as a real-time image-guidance method for prostate radiotherapy.

  1. Screening for Prostate Cancer

    MedlinePlus

    ... difficult to assess the effect of lead-time bias on the reported rates. Men with screen-detected ... and Treatment Two poor-quality (high risk of bias) randomized, con- trolled trials initiated in the 1980s ...

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

    PubMed Central

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

    2016-01-01

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

  3. Molecular aspects of prostate cancer with neuroendocrine differentiation

    PubMed Central

    Li, Qi; Zhang, Connie S.

    2016-01-01

    Neuroendocrine differentiation (NED), which is not uncommon in prostate cancer, is increases in prostate cancer after androgen-deprivation therapy (ADT) and generally appears in castration-resistant prostate cancer (CRPC). Neuroendocrine cells, which are found in normal prostate tissue, are a small subset of cells and have unique function in regulating the growth of prostate cells. Prostate cancer with NED includes different types of tumor, including focal NED, pure neuroendocrine tumor or mixed neuroendocrine-adenocarcinoma. Although more and more studies are carried out on NED in prostate cancer, the molecular components that are involved in NED are still poorly elucidated. We review neuroendocrine cells in normal prostate tissue, NED in prostate cancer, terminology of NED and biomarkers used for detecting NED in routine pathological practice. Some recently reported molecular components which drive NED in prostate cancer are listed in the review. PMID:27041934

  4. Synthesis, crystal structure and effect of indeno[1,2-b]indole derivatives on prostate cancer in vitro. Potential effect against MMP-9.

    PubMed

    Lobo, Gricela; Monasterios, Melina; Rodrigues, Juan; Gamboa, Neira; Capparelli, Mario V; Martínez-Cuevas, Javier; Lein, Michael; Jung, Klaus; Abramjuk, Claudia; Charris, Jaime

    2015-01-01

    A highly regiospecific synthesis of a series of indenoindoles is reported, together with X-ray studies and their activity against human prostate cancer cells PC-3 and LNCaP in vitro. The most effective compound 7,7-dimethyl-5-[(3,4-dichlorophenyl)]-(4bRS,9bRS)-dihydroxy-4b,5,6,7,8,9bhexahydro-indeno[1,2-b]indole-9,10-dione 7q reduced the viability in both cell lines in a time and dose-dependent manner. Inhibitory effects were also observed on the adhesion, migration, and invasion of the prostate cancer cells as well as on clonogenic possibly by inhibition of MMP-9 activity. Molecular docking of 7q and 6k into MMP-9 human active site was also performed to determine the probable binding mode.

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

    ClinicalTrials.gov

    2016-06-22

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

  6. Increased chemopreventive effect by combining arctigenin, green tea polyphenol and curcumin in prostate and breast cancer cells.

    PubMed

    Wang, Piwen; Wang, Bin; Chung, Seyung; Wu, Yanyuan; Henning, Susanne M; Vadgama, Jaydutt V

    2014-08-01

    The low bioavailability of most flavonoids limits their application as anti-carcinogenic agents in humans. A novel approach of treatment with a mixture of bioactive compounds that share molecular anti-carcinogenic targets may enhance the effect on these targets at low concentrations of individual compound, thereby overcoming the limitations of reduced bioavailability. We therefore investigated whether a combination of three natural products arctigenin (Arc), a novel anti-inflammatory lignan from the seeds of Arctium lappa, green tea polyphenol (-)-epigallocatechin gallate (EGCG) and curcumin (Cur) increases the chemopreventive potency of individual compounds. LNCaP prostate cancer and MCF-7 breast cancer cells were treated with 2-4 mg/L (about 5-10μM) Cur, 1μM Arc and 40μM EGCG alone or in combination for 48h. In both cell lines treatment with the mixture of Cur, Arc and EGCG synergistically increased the antiproliferative effect. In LNCaP cells both Arc and EGCG increased the pro-apoptotic effect of Cur. Whereas in MCF-7 cells Arc increased the cell apoptosis of Cur while EGCG enhanced cell cycle arrest of Cur at G0/G1 phase. The strongest effects on cell cycle arrest and apoptosis were achieved by combining all three compounds in both cell lines. The combination treatment significantly increased the ratio of Bax to Bcl-2 proteins, decreased the activation of NFκB, PI3K/Akt and Stat3 pathways and cell migration compared to individual treatment. These results warrant in vivo studies to confirm the efficacy of this novel regimen by combining Arc and EGCG with Cur to enhance chemoprevention in both prostate and breast cancer.

  7. Increased chemopreventive effect by combining arctigenin, green tea polyphenol and curcumin in prostate and breast cancer cells.

    PubMed

    Wang, Piwen; Wang, Bin; Chung, Seyung; Wu, Yanyuan; Henning, Susanne M; Vadgama, Jaydutt V

    2014-08-01

    The low bioavailability of most flavonoids limits their application as anti-carcinogenic agents in humans. A novel approach of treatment with a mixture of bioactive compounds that share molecular anti-carcinogenic targets may enhance the effect on these targets at low concentrations of individual compound, thereby overcoming the limitations of reduced bioavailability. We therefore investigated whether a combination of three natural products arctigenin (Arc), a novel anti-inflammatory lignan from the seeds of Arctium lappa, green tea polyphenol (-)-epigallocatechin gallate (EGCG) and curcumin (Cur) increases the chemopreventive potency of individual compounds. LNCaP prostate cancer and MCF-7 breast cancer cells were treated with 2-4 mg/L (about 5-10μM) Cur, 1μM Arc and 40μM EGCG alone or in combination for 48h. In both cell lines treatment with the mixture of Cur, Arc and EGCG synergistically increased the antiproliferative effect. In LNCaP cells both Arc and EGCG increased the pro-apoptotic effect of Cur. Whereas in MCF-7 cells Arc increased the cell apoptosis of Cur while EGCG enhanced cell cycle arrest of Cur at G0/G1 phase. The strongest effects on cell cycle arrest and apoptosis were achieved by combining all three compounds in both cell lines. The combination treatment significantly increased the ratio of Bax to Bcl-2 proteins, decreased the activation of NFκB, PI3K/Akt and Stat3 pathways and cell migration compared to individual treatment. These results warrant in vivo studies to confirm the efficacy of this novel regimen by combining Arc and EGCG with Cur to enhance chemoprevention in both prostate and breast cancer. PMID:25243063

  8. Prostate Cancer Stem Cells: Research Advances

    PubMed Central

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

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

  9. Prostate Cancer Stem Cells: Research Advances.

    PubMed

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

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

  10. EDB Fibronectin Specific Peptide for Prostate Cancer Targeting.

    PubMed

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

    2015-05-20

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

  11. Radium-223 for Advanced Prostate Cancer

    Cancer.gov

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

  12. Abiraterone Improves Survival in Metastatic Prostate Cancer

    Cancer.gov

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

  13. A Urologist's Personal View of Prostate Cancer.

    PubMed

    Schellhammer, Paul F

    2016-09-01

    A urologist's personal experience with multiple surgical, hormonal, and radio/immunotherapeutic options for the treatment of advanced prostate cancer and thoughts on the role of old and new therapies. PMID:27635283

  14. Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers: The Selenium and Vitamin E Cancer Prevention Trial (SELECT)

    PubMed Central

    Lippman, Scott M.; Klein, Eric A.; Goodman, Phyllis J.; Lucia, M. Scott; Thompson, Ian M.; Ford, Leslie G.; Parnes, Howard L.; Minasian, Lori M.; Gaziano, J. Michael; Hartline, Jo Ann; Parsons, J. Kellogg; Bearden, James D.; Crawford, E. David; Goodman, Gary E.; Claudio, Jaime; Winquist, Eric; Cook, Elise D.; Karp, Daniel D.; Walther, Philip; Lieber, Michael M.; Kristal, Alan R.; Darke, Amy K.; Arnold, Kathryn B.; Ganz, Patricia A.; Santella, Regina M.; Albanes, Demetrius; Taylor, Philip R.; Probstfield, Jeffrey L.; Jagpal, T. J.; Crowley, John J.; Meyskens, Frank L.; Baker, Laurence H.; Coltman, Charles A.

    2013-01-01

    Context Secondary analyses of two randomized controlled trials (RCTs) and supportive epidemiologic and preclinical indicated the potential of selenium and vitamin E for preventing prostate cancer. Objective To determine whether selenium or vitamin E or both could prevent prostate cancer with little or no toxicity in relatively healthy men. Design, Setting, and Participants Randomization of a planned 32,400 men to selenium, vitamin E, selenium plus vitamin E, and placebo in a double-blinded fashion. Participants were recruited and followed in community practices, local hospitals and HMOs, and tertiary cancer centers in the United States, Canada and Puerto Rico. Baseline eligibility included 50 years or older (African American) or 55 years or older (all others), a serum prostate-specific antigen (PSA) ≤ 4 ng/mL, and a digital rectal examination (DRE) not suspicious for prostate cancer. Between 2001 and 2004, 35,533 men (10% more than planned because of a faster-than-expected accrual rate) were randomly assigned to the four study arms, which were well balanced with respect to all potentially important risk factors. Interventions Oral selenium (200 µg/day from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/day of all rac-α-tocopheryl acetate) and matched selenium placebo, or the two combined or placebo plus placebo for a planned minimum of 7 and maximum of 12 years. Main Outcome Measures Prostate cancer (as determined by routine community diagnostic standards) and prespecified secondary outcomes including lung, colorectal and overall cancer. Results Study supplements were discontinued at the recommendation of the Data and Safety Monitoring Committee at a planned 7-year interim analysis because the evidence convincingly demonstrated no benefit from either study agent (p < 0.0001) and no possibility of a benefit to the planned degree with additional follow-up. As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17 and 7

  15. [Use of gold radionuclide markers implanted into the prostate for image-guided radiotherapy in prostate cancer: side effects caused by the marker implantation].

    PubMed

    Kliton, Jorgo; Ágoston, Péter; Szabó, Zoltán; Major, Tibor; Polgár, Csaba

    2014-09-01

    The purpose of the study was to introduce the use of the gold radiopaque markers implanted into the prostate for image-guided radiotherapy of prostate cancer patients and to present the side effects caused by the marker implantation. Between November 2011 and November 2013, three radiopaque, gold-plated markers (Best Medical International, Springfield, VA, USA, 1.0 mm x 3.0 mm) were implanted transperineally into the prostate of 60 patients under transrectal ultrasound guidance. Local anaesthesia was performed in all patients. A week after the procedure the patients filled in a questionnaire regarding the pain, dysuria, urinary frequency, nycturia, rectal bleeding, haematuria, haematospermia or fever symptoms caused by the implantation. The pain caused by the intervention was scored on a 1-10 scale, where 1 was a very weak and 10 was an unbearable pain. Ten days after the implantation a treatment planning CT was performed and subsequently patients started intensity-modulated radiation therapy (IMRT) within one week. During the treatments markers were used for daily verification and correction of patient's setup. No patients experienced fever or infection. Based on the questionnaires nobody experienced dysuria or rectal bleeding after implantation. Among the 60 patients studied, five (8 %) had haematospermia, nine (15 %) haematuria, which lasted in average of 3.4 and 1.8 days, respectively. The average pain score on 1-10 scale was 4.2 (range: 0-9). After the marker implantation 18 patients (30%) reported less, 10 patients (17%) more, and 27 patients (45%) equal amount of pain compared to biopsy. Five patients, who had a biopsy performed under general anaesthesia, did not answer this question. None of the patients needed analgesics after implantation. The gold marker implantation implemented for image-guided radiotherapy was well tolerated under a local anaesthesia. The complications were limited, rate and frequency of perioperative pain was comparable to the pain

  16. SOCS2 correlates with malignancy and exerts growth-promoting effects in prostate cancer

    PubMed Central

    Hoefer, Julia; Kern, Johann; Ofer, Philipp; Eder, Iris E; Schäfer, Georg; Dietrich, Dimo; Kristiansen, Glen; Geley, Stephan; Rainer, Johannes; Gunsilius, Eberhard; Klocker, Helmut; Culig, Zoran; Puhr, Martin

    2014-01-01

    Deregulation of cytokine and growth factor signaling due to an altered expression of endogenous regulators is well recognized in prostate cancer (PCa) and other cancers. Suppressor of cytokine signaling 2 (SOCS2) is a key regulator of the GH, IGF, and prolactin signaling pathways that have been implicated in carcinogenesis. In this study, we evaluated the expression patterns and functional significance of SOCS2 in PCa. Protein expression analysis employing tissue microarrays from two independent patient cohorts revealed a significantly enhanced expression in tumor tissue compared with benign tissue as well as association with Gleason score and disease progression. In vitro and in vivo assays uncovered the involvement of SOCS2 in the regulation of cell growth and apoptosis. Functionally, SOCS2 knockdown inhibited PCa cell proliferation and xenograft growth in a CAM assay. Decreased cell growth after SOCS2 downregulation was associated with cell-cycle arrest and apoptosis. In addition, we proved that SOCS2 expression is significantly elevated upon androgenic stimulation in androgen receptor (AR)-positive cell lines, providing a possible mechanistic explanation for high SOCS2 levels in PCa tissue. Consequently, SOCS2 expression correlated with AR expression in the malignant tissue of patients. On the whole, our study linked increased SOCS2 expression in PCa with a pro-proliferative role in vitro and in vivo. PMID:24280133

  17. Anti-cancer effect of ursolic acid activates apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer

    PubMed Central

    Gai, Wen-Tao; Yu, Da-Peng; Wang, Xin-Sheng; Wang, Pei-Tao

    2016-01-01

    Ursolic acid is a type of pentacyclic triterpene compound with multiple pharmacological activities including cancer resistance, protection from liver injury, antisepsis, anti-inflammation and antiviral activity. The present study aimed to investigate the anticancer effect of ursolic acid. Ursolic acid activates cell apoptosis and its pro-apoptotic mechanism remains to be fully elucidated. Cell Counting kit-8 assays, flow cytometric analysis and analysis of caspase-3 and caspase-9 activity were used to estimate the anticancer effect of ursolic acid on DU145 prostate cancer cells. The protein expression of cytochrome c, rho-associated protein kinase (ROCK), phosphatase and tensin homolog (PTEN) and cofilin-1 were examined using western blot analysis. In the present study, ursolic acid significantly suppressed cell growth and induced apoptosis, as well as increasing caspase-3 and caspase-9 activities of DU145 cells. Furthermore, cytoplasmic and mitochondrial cytochrome c protein expression was significantly activated and suppressed, respectively, by ursolic acid. Ursolic acid significantly suppressed the ROCK/PTEN signaling pathway and inhibited cofilin-1 protein expression in DU145 cells. The results of the present study indicate that the anticancer effect of ursolic acid activates cell apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer.

  18. Anti-cancer effect of ursolic acid activates apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer

    PubMed Central

    Gai, Wen-Tao; Yu, Da-Peng; Wang, Xin-Sheng; Wang, Pei-Tao

    2016-01-01

    Ursolic acid is a type of pentacyclic triterpene compound with multiple pharmacological activities including cancer resistance, protection from liver injury, antisepsis, anti-inflammation and antiviral activity. The present study aimed to investigate the anticancer effect of ursolic acid. Ursolic acid activates cell apoptosis and its pro-apoptotic mechanism remains to be fully elucidated. Cell Counting kit-8 assays, flow cytometric analysis and analysis of caspase-3 and caspase-9 activity were used to estimate the anticancer effect of ursolic acid on DU145 prostate cancer cells. The protein expression of cytochrome c, rho-associated protein kinase (ROCK), phosphatase and tensin homolog (PTEN) and cofilin-1 were examined using western blot analysis. In the present study, ursolic acid significantly suppressed cell growth and induced apoptosis, as well as increasing caspase-3 and caspase-9 activities of DU145 cells. Furthermore, cytoplasmic and mitochondrial cytochrome c protein expression was significantly activated and suppressed, respectively, by ursolic acid. Ursolic acid significantly suppressed the ROCK/PTEN signaling pathway and inhibited cofilin-1 protein expression in DU145 cells. The results of the present study indicate that the anticancer effect of ursolic acid activates cell apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer. PMID:27698874

  19. Gabapentin, an Analgesic Used Against Cancer-Associated Neuropathic Pain: Effects on Prostate Cancer Progression in an In Vivo Rat Model.

    PubMed

    Bugan, Ilknur; Karagoz, Zeynep; Altun, Seyhan; Djamgoz, Mustafa B A

    2016-03-01

    A major problem associated with clinical management of cancer is controlling the accompanying pain, and various analgesics are in common use for this purpose. Recent evidence suggests that some of the targets of analgesics, such as ion channels and receptors, may also be involved in the cancer process, thereby raising the possibility that such use of some analgesics may impact upon cancer itself. The main aim of this study was to determine whether gabapentin, a common adjuvant analgesic in current use against cancer-associated neuropathic pain, would affect tumour development and progression in vivo. The Dunning rat model of prostate cancer was used. Strongly metastatic Mat-LyLu cells were implanted subcutaneously into syngeneic Copenhagen rats which were then treated every other day with 4.6-16.8 μg/kg gabapentin by gavage. Primary tumourigenesis was monitored daily. Lung metastases were counted and measured after killing the rats 21 days later. Gabapentin had no effect on primary tumourigenesis but produced dose-dependent effects on lung metastasis. Whilst 4.6 μg/kg had no effect, 9.1 μg/kg gabapentin decreased the number of lung metastases significantly by 64%. In contrast, 16.8 μg/kg gabapentin promoted metastasis significantly by 112% and showed a strong tendency to shorten mean survival time. It is concluded that gabapentin prescribed to cancer patients against pain could impact upon the cancer process itself.

  20. Gabapentin, an Analgesic Used Against Cancer-Associated Neuropathic Pain: Effects on Prostate Cancer Progression in an In Vivo Rat Model.

    PubMed

    Bugan, Ilknur; Karagoz, Zeynep; Altun, Seyhan; Djamgoz, Mustafa B A

    2016-03-01

    A major problem associated with clinical management of cancer is controlling the accompanying pain, and various analgesics are in common use for this purpose. Recent evidence suggests that some of the targets of analgesics, such as ion channels and receptors, may also be involved in the cancer process, thereby raising the possibility that such use of some analgesics may impact upon cancer itself. The main aim of this study was to determine whether gabapentin, a common adjuvant analgesic in current use against cancer-associated neuropathic pain, would affect tumour development and progression in vivo. The Dunning rat model of prostate cancer was used. Strongly metastatic Mat-LyLu cells were implanted subcutaneously into syngeneic Copenhagen rats which were then treated every other day with 4.6-16.8 μg/kg gabapentin by gavage. Primary tumourigenesis was monitored daily. Lung metastases were counted and measured after killing the rats 21 days later. Gabapentin had no effect on primary tumourigenesis but produced dose-dependent effects on lung metastasis. Whilst 4.6 μg/kg had no effect, 9.1 μg/kg gabapentin decreased the number of lung metastases significantly by 64%. In contrast, 16.8 μg/kg gabapentin promoted metastasis significantly by 112% and showed a strong tendency to shorten mean survival time. It is concluded that gabapentin prescribed to cancer patients against pain could impact upon the cancer process itself. PMID:26335695

  1. Dietary Polyphenols in Prevention and Treatment of Prostate Cancer

    PubMed Central

    Lall, Rahul K.; Syed, Deeba N.; Adhami, Vaqar M.; Khan, Mohammad Imran; Mukhtar, Hasan

    2015-01-01

    Prostate cancer is the most prevalent disease affecting males in many Western countries, with an estimated 29,480 deaths in 2014 in the US alone. Incidence rates for prostate cancer deaths have been decreasing since the early 1990s in men of all races/ethnicities, though they remain about 60% higher in African Americans than in any other group. The relationship between dietary polyphenols and the prevention of prostate cancer has been examined previously. Although results are sometimes inconsistent and variable, there is a general agreement that polyphenols hold great promise for the future management of prostate cancer. Various dietary components, including polyphenols, have been shown to possess anti-cancer properties. Generally considered as non-toxic, dietary polyphenols act as key modulators of signaling pathways and are therefore considered ideal chemopreventive agents. Besides possessing various anti-tumor properties, dietary polyphenols also contribute to epigenetic changes associated with the fate of cancer cells and have emerged as potential drugs for therapeutic intervention. Polyphenols have also been shown to affect post-translational modifications and microRNA expressions. This article provides a systematic review of the health benefits of selected dietary polyphenols in prostate cancer, especially focusing on the subclasses of polyphenols, which have a great effect on disease prevention and treatment. PMID:25654230

  2. Dietary polyphenols in prevention and treatment of prostate cancer.

    PubMed

    Lall, Rahul K; Syed, Deeba N; Adhami, Vaqar M; Khan, Mohammad Imran; Mukhtar, Hasan

    2015-02-03

    Prostate cancer is the most prevalent disease affecting males in many Western countries, with an estimated 29,480 deaths in 2014 in the US alone. Incidence rates for prostate cancer deaths have been decreasing since the early 1990s in men of all races/ethnicities, though they remain about 60% higher in African Americans than in any other group. The relationship between dietary polyphenols and the prevention of prostate cancer has been examined previously. Although results are sometimes inconsistent and variable, there is a general agreement that polyphenols hold great promise for the future management of prostate cancer. Various dietary components, including polyphenols, have been shown to possess anti-cancer properties. Generally considered as non-toxic, dietary polyphenols act as key modulators of signaling pathways and are therefore considered ideal chemopreventive agents. Besides possessing various anti-tumor properties, dietary polyphenols also contribute to epigenetic changes associated with the fate of cancer cells and have emerged as potential drugs for therapeutic intervention. Polyphenols have also been shown to affect post-translational modifications and microRNA expressions. This article provides a systematic review of the health benefits of selected dietary polyphenols in prostate cancer, especially focusing on the subclasses of polyphenols, which have a great effect on disease prevention and treatment.

  3. AR function in promoting metastatic prostate cancer

    PubMed Central

    Augello, Michael A.; Den, Robert B.

    2015-01-01

    Prostate cancer (PCa) remains a leading cause of cancer-related death in the USA. While localized lesions are effectively treated through radical prostatectomy and/or radiation therapy, treatment for metastatic disease leverages the addiction of these tumors on the androgen receptor (AR) signaling axis for growth and disease progression. Though initially effective, tumors resistant to AR-directed therapeutics ultimately arise (a stage of the disease known as castration-resistant prostate cancer) and are responsible for PCa-specific mortality. Importantly, an abundance of clinical and preclinical evidence strongly implicates AR signaling cascades in the development of metastatic disease in both early and late stages, and thus a concerted effort has been made to delineate the AR-specific programs that facilitate progression to metastatic PCa. A multitude of downstream AR targets as well as critical AR cofactors have been identified which impinge upon both the AR pathway as well as associated metastatic phenotypes. This review will highlight the functional significance of these pathways to disseminated disease and define the molecular underpinnings behind these unique, AR-driven, metastatic signatures. PMID:24425228

  4. Losartan sensitizes selectively prostate cancer cell to ionizing radiation.

    PubMed

    Yazdannejat, H; Hosseinimehr, S J; Ghasemi, A; Pourfallah, T A; Rafiei, A

    2016-01-11

    Losartan is an angiotensin II receptor (AT-II-R) blocker that is widely used by human for blood pressure regulation. Also, it has antitumor property. In this study, we investigated the radiosensitizing effect of losartan on cellular toxicity induced by ionizing radiation on prostate cancer and non-malignant fibroblast cells. Human prostate cancer (DU-145) and human non-malignant fibroblast cells (HFFF2) were treated with losartan at different concentrations (0.5, 1, 10, 50 and 100 µM) and then these cells were exposed to ionizing radiation. The cell proliferation was determined using MTT assay. Our results showed that losartan exhibited antitumor effect on prostate cancer cells; it was reduced cell survival to 66% at concentration 1 µM. Losartan showed an additive killing effect in combination with ionizing radiation on prostate cancer cell. The cell proliferation was reduced to 54% in the prostate cancer cells treated with losartan at concentration 1 µM in combination with ionizing radiation. Losartan did not exhibit any toxicity on HFFF2 cell. This result shows a promising effect of losartan on enhancement of therapeutic effect of ionizing radiation in patients during therapy.

  5. Epidemiology, etiology, diagnosis and treatment of prostate cancer.

    PubMed

    Daniyal, Muhammad; Siddiqui, Zamir Ali; Akram, Muhammad; Asif, H M; Sultana, Sabira; Khan, Asmatullah

    2014-01-01

    Prostate cancer is more common in men over the age of 65 years. There are 15% cases with positive family history of prostate cancer Worldwide. Prostate cancer is the second leading cause of death among the U.S. men. Prostate cancer incidence is strongly related to age with the highest rates in older man. Globally millions of people are suffering from this disease. This study aims to provide awareness about prostate cancer as well as an updated knowledge about the epidemiology, etiology, diagnosis and treatment of prostate cancer.

  6. Rectal wall sparing by dosimetric effect of rectal balloon used during intensity-modulated radiation therapy (IMRT) for prostate cancer.

    PubMed

    Teh, Bin S; Dong, Lei; McGary, John E; Mai, Wei-Yuan; Grant, Walter; Butler, E Brian

    2005-01-01

    The use of an air-filled rectal balloon has been shown to decrease prostate motion during prostate radiotherapy. However, the perturbation of radiation dose near the air-tissue interfaces has raised clinical concerns of underdosing the prostate gland. The aim of this study was to investigate the dosimetric effects of an air-filled rectal balloon on the rectal wall/mucosa and prostate gland. Clinical rectal toxicity and dose-volume histogram (DVH) were also assessed to evaluate for any correlation. A film phantom was constructed to simulate the 4-cm diameter air cavity created by a rectal balloon. Kodak XV2 films were utilized to measure and compare dose distribution with and without air cavity. To study the effect in a typical clinical situation, the phantom was computed tomography (CT) scanned on a Siemens DR CT scanner for intensity-modulated radiation therapy (IMRT) treatment planning. A target object was drawn on the phantom CT images to simulate the treatment of prostate cancer. Because patients were treated in prone position, the air cavity was situated superiorly to the target. The treatment used a serial tomotherapy technique with the Multivane Intensity Modulating Collimator (MIMiC) in arc treatment mode. Rectal toxicity was assessed in 116 patients treated with IMRT to a mean dose of 76 Gy over 35 fractions (2.17-Gy fraction size). They were treated in the prone position, immobilized using a Vac-Loktrade mark bag and carrier-box system. Rectal balloon inflated with 100 cc of air was used for prostate gland immobilization during daily treatment. Rectal toxicity was assessed using modifications of the Radiation Therapy Oncology Group (RTOG) and late effects Normal Tissue Task Force (LENT) scales systems. DVH of the rectum was also evaluated. From film dosimetry, there was a dose reduction at the distal air-tissue interface as much as 60% compared with the same geometry without the air cavity for 15-MV photon beam and 2x2-cm field size. The dose beyond the

  7. The politics of prostate cancer screening.

    PubMed

    Kaffenberger, Samuel D; Penson, David F

    2014-05-01

    The controversial recent recommendation by the United States Preventive Services Task Force (USPSTF) against prostate-specific antigen (PSA) screening for early-stage prostate cancer has caused much debate. Whereas USPSTF recommendations against routine screening mammography in younger women resulted in fierce public outcry and eventual alteration in the language of the recommendation, the same public and political response has not been seen with PSA screening for prostate cancer. It is of paramount importance to ensure improved efficiency and transparency of the USPSTF recommendation process, and resolution of concerns with the current USPSTF recommendation against PSA screening for all ages. PMID:24725487

  8. [An unusual presentation of prostate cancer].

    PubMed

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

    1996-01-01

    The authors report an uncommon case of a 74-year old man with prostatic cancer revealed by pelvic mass. Ultrasound exam and CT-scan showed a bilateral laterorectal mass with high density. Presence of such a mass in an old patient is very suggestive of lymph nodes than retroperitoneal tumor. Serum prostate specific antigen (PSA) is rather helpful in such conditions. Biopsy of the mass allows confirmation of the prostatic cancer diagnosis. Bilateral Surgical pulpectomy is performed in combination with oral hormonal therapy. Follow-up after 6 months showed a good course or ultrasound exam and PSA level. PMID:8975593

  9. Cost-effectiveness analysis of abiraterone and sipuleucel-T in asymptomatic metastatic castration-resistant prostate cancer.

    PubMed

    Gong, Cynthia L; Hay, Joel W

    2014-10-01

    Of patients diagnosed with prostate cancer, 0% to 20% experience disease progression to metastatic castration-resistant prostate cancer (mCRPC). Recently, 4 novel therapies have been introduced for the treatment of mCRPC; of these, abiraterone and sipuleucel-T have been studied in the asymptomatic, pre-docetaxel population. Both have shown clinical benefits compared with placebo. This study evaluated the cost-effectiveness of abiraterone acetate and sipuleucel-T compared with prednisone in asymptomatic, pre-docetaxel mCRPC from a US societal perspective. A Markov model was constructed to simulate stable disease, progressed disease, and death. Survival and event rates were derived from published clinical trial data. Costs were derived from the literature and government reimbursement schedules. Outcomes were measured as average cost-effectiveness ratios (ACERs), incremental cost-effectiveness ratios (ICERs), and net monetary benefits (NMBs). One-way and probabilistic sensitivity analyses were conducted to test the robustness of the model. The base-case ACER was $114K/quality-adjusted life-years (QALY) for abiraterone, $85K/QALY for sipuleucel-T, and $31K/QALY for prednisone. The base-case ICER was $389K/QALY for abiraterone and $547K/QALY for sipuleucel-T. Prednisone dominates both abiraterone and sipuleucel-T in terms of NMB at willingness-to-pay (WTP) thresholds of $400K or less. One-way sensitivity analyses revealed that the model was most sensitive to overall survival and utility inputs. Probabilistic sensitivity analyses showed abiraterone to be cost-effective 50% or more of the time at a WTP of greater than $400K, whereas sipuleucel-T was cost-effective 50% or more of the time at a WTP of greater than $270K. Neither abiraterone nor sipuleucel-T was found to be cost-effective compared with prednisone in the treatment of asymptomatic, pre-docetaxel mCRPC. PMID:25313181

  10. Integration of Prostate Cancer Clinical Data Using an Ontology

    PubMed Central

    Min, Hua; Manion, Frank J.; Goralczyk, Elizabeth; Wong, Yu-Ning; Ross, Eric; Beck, J. Robert

    2009-01-01

    It is increasingly important for investigators to efficiently and effectively access, interpret, and analyze the data from diverse biological, literature, and annotation sources in a unified way. The heterogeneity of biomedical data and the lack of metadata are the primary sources of the difficulty for integration, presenting major challenges to effective search and retrieval of the information. As a proof of concept, the Prostate Cancer Ontology (PCO) is created for the development of the Prostate Cancer Information System (PCIS). PCIS is applied to demonstrate how the ontology is utilized to solve the semantic heterogeneity problem from the integration of two prostate cancer related database systems at the Fox Chase Cancer Center. As the results of the integration process, the semantic query language SPARQL is applied to perform the integrated queries across the two database systems based on PCO. PMID:19497389

  11. Integration of prostate cancer clinical data using an ontology.

    PubMed

    Min, Hua; Manion, Frank J; Goralczyk, Elizabeth; Wong, Yu-Ning; Ross, Eric; Beck, J Robert

    2009-12-01

    It is increasingly important for investigators to efficiently and effectively access, interpret, and analyze the data from diverse biological, literature, and annotation sources in a unified way. The heterogeneity of biomedical data and the lack of metadata are the primary sources of the difficulty for integration, presenting major challenges to effective search and retrieval of the information. As a proof of concept, the Prostate Cancer Ontology (PCO) is created for the development of the Prostate Cancer Information System (PCIS). PCIS is applied to demonstrate how the ontology is utilized to solve the semantic heterogeneity problem from the integration of two prostate cancer related database systems at the Fox Chase Cancer Center. As the results of the integration process, the semantic query language SPARQL is applied to perform the integrated queries across the two database systems based on PCO.

  12. Management of low risk and low PSA prostate cancer: long term results from the prostate cancer intervention versus observation trial.

    PubMed

    Wilt, Timothy J

    2014-01-01

    Management of localized prostate cancer is controversial due in part to the lack of randomized controlled trial information in men diagnosed with prostate specific antigen (PSA) testing. Men with low risk or low PSA (<10 ng/ml) prostate cancer comprise up to 70 % of men currently diagnosed. Evidence suggests an excellent long-term prognosis with observation though nearly 90 % are treated with surgery (radical prostatectomy), external beam radiation, or brachytherapy. Results from the Prostate cancer Intervention Versus Observation Trial (PIVOT) provide high quality Level 1 evidence that observation compared to surgery results in similar long-term overall and prostate cancer survival, prevention of bone metastases and avoidance of surgery related harms. Combined with emerging evidence from screening, natural history, decision analysis and cost-effectiveness modeling studies, these data demonstrate that observation is the preferred treatment option for men with low risk and possibly low PSA prostate cancer. Recommending against PSA testing or, in men who still desire testing, raising thresholds of PSA values used to define abnormal, lengthening intervals between PSA tests and discontinuing testing in men with a life expectancy less than 15 years will reduce diagnostic and treatment related harms without adversely impacting overall or disease specific mortality and morbidity. PMID:24531789

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

    ClinicalTrials.gov

    2016-05-06

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

  14. Growth inhibitory and apoptosis-inducing effects of xanthohumol, a prenylated chalone present in hops, in human prostate cancer cells.

    PubMed

    Deeb, D; Gao, X; Jiang, H; Arbab, A S; Dulchavsky, S A; Gautam, S C

    2010-09-01

    Promotion of apoptosis in cancer cells could potentially lead to the regression and improved prognosis of hormone-refractory prostate cancer. Xanthohumol (XN), a prenylated chalcone-derived from hops, has shown strong antitumorigenic activity towards diverse types of cancer cells. In the present study, the growth-inhibitory and apoptosis-inducing activity of XN was tested in hormone-sensitive and hormone-refractory human prostate cancer cells lines. Cell growth/viability assay (MTS) demonstrated that prostate cancer cells are highly sensitive to XN at a concentration range of 20-40 μM. The primary mode of tumor cell destruction was apoptosis as demonstrated by the binding of annexin V-FITC, cleavage of PARP-1, activation of procaspases -3, -8, and -9, mitochondrial depolarization and release of cytochrome c from mitochondria. Induction of apoptosis by XN was associated with the inhibition of prosurvival Akt, NF-κB and mTOR signaling proteins and NF-κB-regulated anti-apoptotic Bcl-2 and survivin. These studies provide a rationale for clinical evaluation of XN for the treatment of hormone-refractory metastatic prostate cancer. PMID:20944105

  15. Growth Inhibitory and Apoptosis-inducing Effects of Xanthohumol, a Prenylated Chalcone Present in Hops, in Human Prostate Cancer Cells

    PubMed Central

    DEEB, D.; GAO, X.; JIANG, H.; ARBAB, A.S.; DULCHAVSKY, S.A.; GAUTAM, S.C.

    2013-01-01

    Promotion of apoptosis in cancer cells could potentially lead to the regression and improved prognosis of hormone-refractory prostate cancer. Xanthohumol (XN), a prenylated chalcone-derived from hops, has shown strong antitumorigenic activity towards diverse types of cancer cells. In the present study, the growth-inhibitory and apoptosis-inducing activity of XN was tested in hormone-sensitive and hormone-refractory human prostate cancer cells lines. Cell growth/viability assay (MTS) demonstrated that prostate cancer cells are highly sensitive to XN at a concentration range of 20-40 μM. The primary mode of tumor cell destruction was apoptosis as demonstrated by the binding of annexin V-FITC, cleavage of PARP-1, activation of procaspases -3, -8, and -9, mitochondrial depolarization and release of cytochrome c from mitochondria. Induction of apoptosis by XN was associated with the inhibition of prosurvival Akt, NF-κB and mTOR signaling proteins and NF-κB-regulated anti-apoptotic Bcl-2 and survivin. These studies provide a rationale for clinical evaluation of XN for the treatment of hormone-refractory metastatic prostate cancer. PMID:20944105

  16. Oncolytic adenovirus-mediated therapy for prostate cancer.

    PubMed

    Sweeney, Katrina; Halldén, Gunnel

    2016-01-01

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

  17. Oncolytic adenovirus-mediated therapy for prostate cancer

    PubMed Central

    Sweeney, Katrina; Halldén, Gunnel

    2016-01-01

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

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

    Cancer.gov

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

  19. Blood lipids and prostate cancer: a Mendelian randomization analysis.

    PubMed

    Bull, Caroline J; Bonilla, Carolina; Holly, Jeff M P; Perks, Claire M; Davies, Neil; Haycock, Philip; Yu, Oriana Hoi Yun; Richards, J Brent; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Amin Al Olama, Ali; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; MacInnis, Robert J; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G; Travis, Ruth C; Neal, David; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Micheal, Agnieszka; Pandha, Hardev; Smith, George Davey; Lewis, Sarah J; Martin, Richard M

    2016-06-01

    Genetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL consortium were analyzed. Allele scores based on single nucleotide polymorphisms (SNPs) previously reported to be uniquely associated with each of low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels, were first validated in an independent dataset, and then entered into logistic regression models to estimate the presence (and direction) of any causal effect of each lipid trait on prostate cancer risk. There was weak evidence for an association between the LDL genetic score and cancer grade: the odds ratio (OR) per genetically instrumented standard deviation (SD) in LDL, comparing high- (≥7 Gleason score) versus low-grade (<7 Gleason score) cancers was 1.50 (95% CI: 0.92, 2.46; P = 0.11). A genetically instrumented SD increase in TGs was weakly associated with stage: the OR for advanced versus localized cancer per unit increase in genetic risk score was 1.68 (95% CI: 0.95, 3.00; P = 0.08). The rs12916-T variant in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was inversely associated with prostate cancer (OR: 0.97; 95% CI: 0.94, 1.00; P = 0.03). In conclusion, circulating lipids, instrumented by our genetic risk scores, did not appear to alter prostate cancer risk. We found weak evidence that higher LDL and TG levels increase aggressive prostate cancer risk, and that a variant in HMGCR (that mimics the LDL lowering effect of statin drugs) reduces risk. However, inferences are limited by sample size and evidence of pleiotropy. PMID:26992435

  20. Localized prostate cancer treatment decision-making information online: improving its effectiveness and dissemination for nonprofit and government-supported organizations.

    PubMed

    Silk, Kami J; Perrault, Evan K; Nazione, Samantha; Pace, Kristin; Hager, Polly; Springer, Steven

    2013-12-01

    The current study reports findings from evaluation research conducted to identify how online prostate cancer treatment decision-making information can be both improved and more effectively disseminated to those who need it most. A multi-method, multi-target approach was used and guided by McGuire's Communication Matrix Model. Focus groups (n = 31) with prostate cancer patients and their family members, and in-depth interviews with physicians (n = 8), helped inform a web survey (n = 89). Results indicated that physicians remain a key information source for medical advice and the Internet is a primary channel used to help make informed prostate cancer treatment decisions. Participants reported a need for more accessible information related to treatment options and treatment side effects. Additionally, physicians indicated that the best way for agencies to reach them with new information to deliver to patients is by contacting them directly and meeting with them one-on-one. Advice for organizations to improve their current prostate cancer web offerings and further ways to improve information dissemination are discussed.

  1. Localized prostate cancer treatment decision-making information online: improving its effectiveness and dissemination for nonprofit and government-supported organizations.

    PubMed

    Silk, Kami J; Perrault, Evan K; Nazione, Samantha; Pace, Kristin; Hager, Polly; Springer, Steven

    2013-12-01

    The current study reports findings from evaluation research conducted to identify how online prostate cancer treatment decision-making information can be both improved and more effectively disseminated to those who need it most. A multi-method, multi-target approach was used and guided by McGuire's Communication Matrix Model. Focus groups (n = 31) with prostate cancer patients and their family members, and in-depth interviews with physicians (n = 8), helped inform a web survey (n = 89). Results indicated that physicians remain a key information source for medical advice and the Internet is a primary channel used to help make informed prostate cancer treatment decisions. Participants reported a need for more accessible information related to treatment options and treatment side effects. Additionally, physicians indicated that the best way for agencies to reach them with new information to deliver to patients is by contacting them directly and meeting with them one-on-one. Advice for organizations to improve their current prostate cancer web offerings and further ways to improve information dissemination are discussed. PMID:23907786

  2. [Prostate cancer: papillomaviruses as a possible cause].

    PubMed

    Volgareva, G M

    2015-01-01

    Prostate cancer (PC) incidence and mortality are steadily increasing. Causation of PC is not clearly understood; in particular, role of human papillomaviruses (HPV) is still disputable. The review contains analysis of literature data on possible participation of HPV powerful biological carcinogens, in PC genesis. PC incidence increase in persons with immunodeficiency indicates involvement of some infectious agent in the disease etiology. Several research groups communicated HPV DNA finding including that of oncogenic types in PC specimens (transrectal biopsies). There are limited data on the occurrence of oncogenic HPV 16 oncoprotein E7 in such specimens and on its unfavorable effect on disease prognosis. The successful attempt is known to transfect normal human prostate cells with oncogenic HPVDNA in vitro. Epidemiological data on associations of PC with HPV are controversial. It may result from the considered in the present review certain technical peculiarities of these studies. Controlfor serum antibodies to HPV E6 and E7 oncoproteins recognized to indicate HPV-positive tumor growth in an organism has not been performed yet in PC patients. DNA of oncogenic HPV is rather commonly found in organs adjacent to prostate--urethra, rectum, urinary bladder. In the study held in Russia on a group of healthy men examined for sexually transmitted diseases genitourinary HPVinfection was found in every second person; 42% of them harbored oncogenic HPV. Possible participation of oncogenic HPV in PC genesis deserves close attention and further study. PMID:26027277

  3. [Prostate cancer: papillomaviruses as a possible cause].

    PubMed

    Volgareva, G M

    2015-01-01

    Prostate cancer (PC) incidence and mortality are steadily increasing. Causation of PC is not clearly understood; in particular, role of human papillomaviruses (HPV) is still disputable. The review contains analysis of literature data on possible participation of HPV powerful biological carcinogens, in PC genesis. PC incidence increase in persons with immunodeficiency indicates involvement of some infectious agent in the disease etiology. Several research groups communicated HPV DNA finding including that of oncogenic types in PC specimens (transrectal biopsies). There are limited data on the occurrence of oncogenic HPV 16 oncoprotein E7 in such specimens and on its unfavorable effect on disease prognosis. The successful attempt is known to transfect normal human prostate cells with oncogenic HPVDNA in vitro. Epidemiological data on associations of PC with HPV are controversial. It may result from the considered in the present review certain technical peculiarities of these studies. Controlfor serum antibodies to HPV E6 and E7 oncoproteins recognized to indicate HPV-positive tumor growth in an organism has not been performed yet in PC patients. DNA of oncogenic HPV is rather commonly found in organs adjacent to prostate--urethra, rectum, urinary bladder. In the study held in Russia on a group of healthy men examined for sexually transmitted diseases genitourinary HPVinfection was found in every second person; 42% of them harbored oncogenic HPV. Possible participation of oncogenic HPV in PC genesis deserves close attention and further study.

  4. Chemotherapy of prostate cancer: present and future.

    PubMed

    Trump, Donald; Lau, Yiu-Keung

    2003-06-01

    The role of chemotherapy in prostate cancer continues to evolve. In men with symptomatic androgen-independent prostate cancer, significant reduction in pain and analgesic requirements are achievable with mitoxantrone and glucocorticoid combinations compared with glucocorticoids alone. However, survival rates are not improved. Taxane-based combinations with estramustine phosphate or other new agents show promise. Prostate-specific antigen response rates with these combinations appear to be 1.5 to 2 times more frequent than with mitoxantrone-based combinations. Randomized trials of taxane versus mitoxantrone-based therapies are underway. New agents and applications of current agents in adjuvant settings should be explored if survival in men with prostate cancer is to be improved. PMID:12756087

  5. Chemotherapy of prostate cancer: present and future.

    PubMed

    Trump, Donald; Lau, Yiu-Keung

    2003-06-01

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

  6. Zinc as an anti-tumor agent in prostate cancer and in other cancers.

    PubMed

    Franklin, Renty B; Costello, Leslie C

    2007-07-15

    Human prostate glandular epithelial cells have the unique capability of accumulating high levels of zinc. This is essential to inhibit m-aconitase activity so that citrate can accumulate for secretion into prostatic fluid, which is a major function of the prostate gland. As a result, the Krebs cycle is truncated with the consequence of the lost ATP production that would result from citrate oxidation. The cellular accumulation of zinc also inhibits mitochondrial terminal oxidation and respiration. In addition to these metabolic effects, zinc accumulation exhibits anti-proliferative effects via its induction of mitochondrial apoptogenesis. Zinc accumulation also inhibits the invasive/migration activities in malignant prostate cells. The anti-proliferative effects and the effects on invasion and migration occur through zinc activation of specific intracellular signaling pathways. Consequently, these effects impose anti-tumor actions by zinc. The ability of prostate cells to accumulate zinc is due to the expression and activity of the zinc uptake transporter, ZIP1. To avoid the anti-tumor effects of zinc, in prostate cancer the malignant prostate cells exhibit a silencing of ZIP1 gene expression accompanied by a depletion of cellular zinc. Therefore we regard ZIP1 as a tumor suppressor gene in prostate cancer. In addition to prostate cells, similar tumor suppressor effects of zinc have been identified in several other types of tumors. PMID:17400177

  7. The relationship between prostate-specific antigen and prostate cancer risk: the Prostate Biopsy Collaborative Group

    PubMed Central

    Vickers, Andrew J.; Cronin, Angel M.; Roobol, Monique J.; Hugosson, Jonas; Jones, J. Stephen; Kattan, Michael W.; Klein, Eric; Hamdy, Freddie; Neal, David; Donovan, Jenny; Parekh, Dipen J.; Ankerst, Donna; Bartsch, George; Klocker, Helmut; Horninger, Wolfgang; Benchikh, Amine; Salama, Gilles; Villers, Arnauld; Freedland, Steve J.; Moreira, Daniel M.; Schröder, Fritz H.; Lilja, Hans

    2010-01-01

    PURPOSE The relationship between prostate specific antigen (PSA) level and prostate cancer risk remains subject to fundamental disagreements. We hypothesize that the risk of prostate cancer on biopsy for a given PSA level is affected by identifiable characteristics of the cohort under study. EXPERIMENTAL DESIGN We used data from 5 European and 3 US cohorts of men undergoing biopsy for prostate cancer; six were population-based studies and two were clinical cohorts. The association between PSA and prostate cancer was calculated separately for each cohort using locally-weighted scatterplot smoothing. RESULTS The final data set included 25,772 biopsies and 8,503 cancers. There were gross disparities between cohorts with respect to both the prostate cancer risk at a given PSA level and the shape of the risk curve. These disparities were associated with identifiable differences between cohorts: for a given PSA level, a greater number of biopsy cores increased risk of cancer (odds ratio for >6 vs. 6 core biopsy 1.35; 95% C.I. 1.18, 1.54; p<0.0005); recent screening led to a smaller increase in risk per unit change in PSA (p=0.001 for interaction term) and US cohorts had higher risk than the European cohorts (2.14; 95% C.I. 1.99, 2.30; p<0.0005). CONCLUSIONS Our results suggest that the relationship between PSA and risk of a positive prostate biopsy varies, both in terms of the probability of prostate cancer at a given PSA value and the shape of the risk curve. This poses challenges to the use of PSA-driven algorithms to determine whether biopsy is indicated. PMID:20736330

  8. Anti-cancer effects of novel flavonoid vicenin-2 as a single agent and in synergistic combination with docetaxel in prostate cancer.

    PubMed

    Nagaprashantha, Lokesh Dalasanur; Vatsyayan, Rit; Singhal, Jyotsana; Fast, Spence; Roby, Rhonda; Awasthi, Sanjay; Singhal, Sharad S

    2011-11-01

    The present study was conducted to determine the efficacy of novel flavonoid vicenin-2 (VCN-2), an active constituent of the medicinal herb Ocimum Sanctum Linn or Tulsi, as a single agent and in combination with docetaxel (DTL) in carcinoma of prostate (CaP). VCN-2 effectively induced anti-proliferative, anti-angiogenic and pro-apoptotic effect in CaP cells (PC-3, DU-145 and LNCaP) irrespective of their androgen responsiveness or p53 status. VCN-2 inhibited EGFR/Akt/mTOR/p70S6K pathway along with decreasing c-Myc, cyclin D1, cyclin B1, CDK4, PCNA and hTERT in vitro. VCN-2 reached a level of 2.6±0.3μmol/l in serum after oral administration in mice which reflected that VCN-2 is orally absorbed. The i.v. administration of docetaxel (DTL), current drug of choice in androgen-independent CaP, is associated with dose-limiting toxicities like febrile neutropenia which has lead to characterization of alternate routes of administration and potential combinatorial regimens. In this regard, VCN-2 in combination with DTL synergistically inhibited the growth of prostate tumors in vivo with a greater decrease in the levels of AR, pIGF1R, pAkt, PCNA, cyclin D1, Ki67, CD31, and increase in E-cadherin. VCN-2 has been investigated for radioprotection and anti-inflammatory properties. This is the first study on the anti-cancer effects of VCN-2. In conclusion, our investigations collectively provide strong evidence that VCN-2 is effective against CaP progression along with indicating that VCN-2 and DTL co-administration is more effective than either of the single agents in androgen-independent prostate cancer.

  9. Nigerian foodstuffs with prostate cancer chemopreventive polyphenols

    PubMed Central

    2011-01-01

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

  10. Nigerian foodstuffs with prostate cancer chemopreventive polyphenols.

    PubMed

    Atawodi, Sunday Eneojo

    2011-09-23

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

  11. Oxidative Stress and DNA Methylation in Prostate Cancer

    PubMed Central

    Donkena, Krishna Vanaja; Young, Charles Y. F.; Tindall, Donald J.

    2010-01-01

    The protective effects of fruits, vegetables, and other foods on prostate cancer may be due to their antioxidant properties. An imbalance in the oxidative stress/antioxidant status is observed in prostate cancer patients. Genome oxidative damage in prostate cancer patients is associated with higher lipid peroxidation and lower antioxidant levels. Oxygen radicals are associated with different steps of carcinogenesis, including structural DNA damage, epigenetic changes, and protein and lipid alterations. Epigenetics affects genetic regulation, cellular differentiation, embryology, aging, cancer, and other diseases. DNA methylation is perhaps the most extensively studied epigenetic modification, which plays an important role in the regulation of gene expression and chromatin architecture, in association with histone modification and other chromatin-associated proteins. This review will provide a broad overview of the interplay of oxidative stress and DNA methylation, DNA methylation changes in regulation of gene expression, lifestyle changes for prostate cancer prevention, DNA methylation as biomarkers for prostate cancer, methods for detection of methylation, and clinical application of DNA methylation inhibitors for epigenetic therapy. PMID:20671914

  12. Single nucleotide polymorphisms in DKK3 gene are associated with prostate cancer risk and progression

    PubMed Central

    Kim, Min Su; Lee, Ha Na; Kim, Hae Jong; Myung, Soon Chul

    2015-01-01

    ABSTRACT We had investigated whether sequence variants within DKK3 gene are associated with the development of prostate cancer in a Korean study cohort. We evaluated the association between 53 single nucleotide polymorphisms (SNPs) in the DKK3 gene and prostate cancer risk as well as clinical characteristics (PSA, clinical stage, pathological stage and Gleason score) in Korean men (272 prostate cancer subjects and 173 benign prostate hyperplasia subjects) using unconditional logistic regression analysis. Of the 53 SNPs and 25 common haplotypes, 5 SNPs and 4 haplotypes were associated with prostate cancer risk (P=0.02–0.04); 3 SNPs and 2 haplotypes were significantly associated with susceptibility to prostate cancer, however 2 SNPs and 2 haplotypes exhibited a significant protective effect on prostate cancer. Logistic analyses of the DKK3 gene polymorphisms with several prostate cancer related factors showed that several SNPs were significant; three SNPs and two haplotypes to PSA level, three SNPs and two haplotypes to clinical stage, nine SNPs and two haplotype to pathological stage, one SNP and one haplotypes to Gleason score. To the author's knowledge, this is the first report documenting that DKK3 polymorphisms are not only associated with prostate cancer but also related to prostate cancer-related factors. PMID:26689513

  13. Neural Cell Adhesion Protein CNTN1 Promotes the Metastatic Progression of Prostate Cancer.

    PubMed

    Yan, Judy; Ojo, Diane; Kapoor, Anil; Lin, Xiaozeng; Pinthus, Jehonathan H; Aziz, Tariq; Bismar, Tarek A; Wei, Fengxiang; Wong, Nicholas; De Melo, Jason; Cutz, Jean-Claude; Major, Pierre; Wood, Geoffrey; Peng, Hao; Tang, Damu

    2016-03-15

    Prostate cancer metastasis is the main cause of disease-related mortality. Elucidating the mechanisms underlying prostate cancer metastasis is critical for effective therapeutic intervention. In this study, we performed gene-expression profiling of prostate cancer stem-like cells (PCSC) derived from DU145 human prostate cancer cells to identify factors involved in metastatic progression. Our studies revealed contactin 1 (CNTN1), a neural cell adhesion protein, to be a prostate cancer-promoting factor. CNTN1 knockdown reduced PCSC-mediated tumor initiation, whereas CNTN1 overexpression enhanced prostate cancer cell invasion in vitro and promoted xenograft tumor formation and lung metastasis in vivo. In addition, CNTN1 overexpression in DU145 cells and corresponding xenograft tumors resulted in elevated AKT activation and reduced E-cadherin (CDH1) expression. CNTN1 expression was not readily detected in normal prostate glands, but was clearly evident on prostate cancer cells in primary tumors and lymph node and bone metastases. Tumors from 637 patients expressing CNTN1 were associated with prostate cancer progression and worse biochemical recurrence-free survival following radical prostatectomy (P < 0.05). Collectively, our findings demonstrate that CNTN1 promotes prostate cancer progression and metastasis, prompting further investigation into the mechanisms that enable neural proteins to become aberrantly expressed in non-neural malignancies.

  14. Responder Analysis of the Effects of Denosumab on Bone Mineral Density in Men Receiving Androgen Deprivation Therapy for Prostate Cancer

    PubMed Central

    Egerdie, Blair; Saad, Fred; Smith, Matthew R; Tammela, Teuvo LJ; Heracek, Jiri; Sieber, Paul; Ke, Chunlei; Leder, Benjamin; Dansey, Roger; Goessl, Carsten

    2013-01-01

    Background Men with prostate cancer are at risk of experiencing accelerated bone loss and fractures as a result of androgen deprivation therapy (ADT). Objective We evaluated the effects of denosumab, a fully human monoclonal antibody against RANKL, on preservation of BMD at 3 key skeletal sites (lumbar spine [LS], femoral neck [FN], and total hip [TH]) and the distal radius at 36 months both by responder category and individual responses in a waterfall plot analysis. Design, Setting, and Participants This phase 3, randomized, double-blind study of men with non-metastatic prostate cancer receiving ADT investigated the effects of denosumab on bone mineral density (BMD) and fractures. Patients were treated for 36 months. Intervention Subcutaneous denosumab 60 mg (n=734) or placebo (n=734) every 6 months for up to 36 months. Patients were instructed to take supplemental Calcium and vitamin D. Measurements Primary outcome measure: The percentage change from baseline to month 36 in LS, FN, and TH BMD was measured by dual energy x-ray absorptiometry. BMD at the distal 1/3 radius at 36 months was measured in a sub-study of 309 patients. Results and Limitations At 36 months, significantly more patients in the denosumab arm had increases of >3% BMD from baseline at each site studied compared with placebo (LS, 78% vs 17%; TH, 48% vs 6%; FN, 48% vs 13%; distal 1/3 radius, 40% vs 7%). The percentage of denosumab patients with bone loss at all 3 key BMD sites at month 36 was 1%, as opposed to 42% in placebo arm. At 36 months 69% of denosumab-treated patients had BMD increases at all three sites (LS, TH or FN) compared with 8% of placebo-treated patients. Lower baseline BMD was associated with higher magnitude lumbar spine, femoral neck, and total hip BMD responses to denosumab. Conclusions In men with prostate cancer receiving ADT significantly higher BMD response rates were observed with denosumab vs. placebo. Trial Registration This study is registered with Clinical

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

    PubMed Central

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

    2015-01-01

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

  16. Gleason 6 Prostate Cancer: Translating Biology into Population Health

    PubMed Central

    Eggener, Scott E.; Badani, Ketan; Barocas, Daniel A.; Barrisford, Glen W.; Cheng, Jed-Sian; Chin, Arnold I.; Corcoran, Anthony; Epstein, Jonathan I.; George, Arvin K.; Gupta, Gopal N.; Hayn, Matthew H.; Kauffman, Eric C.; Lane, Brian; Liss, Michael A.; Mirza, Moben; Morgan, Todd M.; Moses, Kelvin; Nepple, Kenneth G.; Preston, Mark A.; Rais-Bahrami, Soroush; Resnick, Matthew J.; Siddiqui, M. Minhaj; Silberstein, Jonathan; Singer, Eric A.; Sonn, Geoffrey A.; Sprenkle, Preston; Stratton, Kelly L.; Taylor, Jennifer; Tomaszewski, Jeffrey; Tollefson, Matt; Vickers, Andrew; White, Wesley M.; Lowrance, William T.

    2015-01-01

    active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes. Conclusions The definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening. PMID:25849602

  17. Targeting prostate cancer based on signal transduction and cell cycle pathways

    PubMed Central

    Lee, John T.; Lehmann, Brian D.; Terrian, David M.; Chappell, William H.; Stivala, Franca; Libra, Massimo; Martelli, Alberto M.; Steelman, Linda S.

    2008-01-01

    Prostate cancer remains a leading cause of death in men despite increased capacity to diagnose at earlier stages. After prostate cancer has become hormone independent, which often occurs after hormonal ablation therapies, it is difficult to effectively treat. Prostate cancer may arise from mutations and dysregulation of various genes involved in regulation signal transduction (e.g., PTEN, Akt, etc.,) and the cell cycle (e.g., p53, p21Cip1, p27Kip1, Rb, etc.,). This review focuses on the aberrant interactions of signal transduction and cell cycle genes products and how they can contribute to prostate cancer and alter therapeutic effectiveness. PMID:18594202

  18. The effect of concurrent androgen deprivation and 3D conformal radiotherapy on prostate volume and clinical organ doses during treatment for prostate cancer

    PubMed Central

    Onal, C; Topkan, E; Efe, E; Yavuz, M; Arslan, G; Yavuz, A

    2009-01-01

    In this study, we investigated the shrinking effect of concurrent three-dimensional conformal radiotherapy (3D-CRT) and androgen deprivation (AD) on prostate volume, and its possible impact on the dose received by the rectum and bladder during the course of 3D-CRT. The difference between the prostatic volumes determined on pre-treatment planning CT (PL-CT) and post-treatment CT (PT-CT) following a 3D-CRT course was assessed in 52 patients with localised prostate carcinoma. The changes in mean prostate volume when compared with PL-CT and PT-CT-based measurements were assessed. The pre- and post-treatment mean prostate volumes for the whole study population were 49.7 cm3 and 41.0 cm3 (p _ 0.02), respectively. The study cohort was divided into two groups depending on the duration of neoadjuvant androgen deprivation (NAD): 23 patients (44.7%) were designated as “short NAD” (≤3 months; SNAD) and the remaining 29 (55.3%) as “long NAD” (>3 months; LNAD). Patients on SNAD experienced a significantly greater reduction in prostate volume compared with those on LNAD (14.1% vs 5.1%; p _ 0.03). A significant increase in rectum V40–60 values in PT-CT compared with PL-CT was demonstrated. LNAD patients had significantly higher rectal V50–70 values at PT-CT compared with the SNAD group. There was a significant decline in V30–V75 bladder values in PT-CT compared with PL-CT in the SNAD group. In conclusion, a higher prostate volume reduction during 3D-CRT was demonstrated when RT planning was performed within 3 months of NAD. However, this reduction and daily organ motion may lead to an unpredictable increase in rectal doses. PMID:19581310

  19. Monocyte-Induced Prostate Cancer Cell Invasion is Mediated by Chemokine ligand 2 and Nuclear Factor-κB Activity

    PubMed Central

    Lindholm, Paul F; Sivapurapu, Neela; Jovanovic, Borko; Kajdacsy-Balla, André

    2015-01-01

    Study Background The tumor microenvironment contains inflammatory cells which can influence cancer growth and progression; however the mediators of these effects vary with different cancer types. The mechanisms by which prostate cancer cells communicate with monocytes to promote cancer progression are incompletely understood. This study tested prostate cancer cell and monocyte interactions that lead to increased prostate cancer cell invasion. Methods We analyzed the prostate cancer cell invasion and NF-κB activity and cytokine expression during interaction with monocyte-lineage cells in co-cultures. The roles of monocyte chemotactic factor (MCP-1/CCL2) and NF-κB activity for co-culture induced prostate cancer invasion were tested. Clinical prostate cancer NF-κB expression was analyzed by immunohistochemistry. Results In co-cultures of prostate cancer cell lines with monocyte-lineage cells, (C-C motif) ligand 2 (CCL2) levels were significantly increased when compared with monocytes or cancer cells cultured alone. Prostate cancer cell invasion was induced by recombinant CCL2 in a dose dependent manner, similar to co-cultures with monocytes. The monocyte-induced prostate cancer cell invasion was inhibited by CCL2 neutralizing antibodies and by the CCR2 inhibitor, RS102895. Prostate cancer cell invasion and CCL2 expression induced in the co-cultures was inhibited by Lactacystin and Bay11-7082 NF-κB inhibitors. Prostate cancer cell NF-κB DNA binding activity depended on CCL2 dose and was inhibited by CCL2 neutralizing antibodies. Clinical prostate cancer NF-κB expression correlated with tumor grade. Conclusions Co-cultures with monocyte-lineage cell lines stimulated increased prostate cancer cell invasion through increased CCL2 expression and increased prostate cancer cell NF-κB activity. CCL2 and NF-κB may be useful therapeutic targets to interfere with inflammation-induced prostate cancer invasion. PMID:26317041

  20. Interstitially implanted I125 for prostate cancer using transrectal ultrasound

    SciTech Connect

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

    1990-11-01

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

  1. Prostate cancer in men of African origin.

    PubMed

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

    2016-02-01

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

  2. A Double Blind, Randomized, Neoadjuvant Study of the Tissue effects of POMx Pills in Men with Prostate Cancer Prior to Radical Prostatectomy

    PubMed Central

    Freedland, Stephen J.; Carducci, Michael; Kroeger, Nils; Partin, Alan; Rao, Jian-yu; Jin, Yusheng; Kerkoutian, Susan; Wu, Hong; Li, Yunfeng; Creel, Patricia; Mundy, Kelly; Gurganus, Robin; Fedor, Helen; King, Serina A.; Zhang, Yanjun; Heber, David; Pantuck, Allan J.

    2013-01-01

    Pomegranates slow prostate cancer xenograft growth and prolong PSA doubling times in single-arm human studies. Pomegranates’ effects on human prostate tissue are understudied. We hypothesized orally administered pomegranate extract (POMx; PomWonderful, Los Angeles, CA) would lower tissue 8-hydroxy-2-deoxyguanosine (8-OHdG), an oxidative stress biomarker. 70 men were randomized to 2 tablets POMx or placebo daily up to 4 weeks prior to radical prostatectomy. Tissue was analyzed for intra-prostatic Urolithin A, a pomegranate metabolite, benign and malignant 8-OHdG, and cancer pS6 kinase, NFκB, and Ki67. Primary end-point was differences in 8-OHdG powered to detect 30% reduction. POMx was associated with 16% lower benign tissue 8-OHdG (p=0.095), which was not statistically significant. POMx was well-tolerated with no treatment-related withdrawals. There were no differences in baseline clinicopathological features between arms. Urolithin A was detected in 21/33 patient in the POMx group vs. 12/35 in the placebo group (p=0.031). Cancer pS6 kinase, NFκB, Ki67, and serum PSA changes were similar between arms. POMx prior to surgery results in pomegranate metabolite accumulation in prostate tissues. Our primary end-point in this modest-sized short-term trial was negative. Future larger longer studies are needed to more definitely test whether POMx reduces prostate oxidative stress as well as further animal testing to better understand the multiple mechanisms through which POMx may alter prostate cancer biology. PMID:23985577

  3. Gene expression in normal-appearing tissue adjacent to prostate cancers are predictive of clinical outcome: evidence for a biologically meaningful field effect

    PubMed Central

    Magi-Galluzzi, Cristina; Maddala, Tara; Falzarano, Sara Moscovita; Cherbavaz, Diana B.; Zhang, Nan; Knezevic, Dejan; Febbo, Phillip G.; Lee, Mark; Lawrence, Hugh Jeffrey; Klein, Eric A.

    2016-01-01

    Purpose We evaluated gene expression in histologically normal-appearing tissue (NT) adjacent to prostate tumor in radical prostatectomy specimens, assessing for biological significance based on prediction of clinical recurrence (cR - metastatic disease or local recurrence). Results A total of 410 evaluable patients had paired tumor and NT. Fortysix genes, representing diverse biological pathways (androgen signaling, stromal response, stress response, cellular organization, proliferation, cell adhesion, and chromatin remodeling) were associated with cR in NT (FDR < 20%), of which 39 concordantly predicted cR in tumor (FDR < 20%). Overall GPS and its stromal response and androgen-signaling gene group components also significantly predicted time to cR in NT (RM-corrected HR/20 units = 1.25; 95% CI: 1.01-1.56; P = 0.024). Experimental Design Expression of 732 genes was measured by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) separately in tumor and adjacent NT specimens from 127 patients with and 374 without cR following radical prostatectomy for T1/T2 prostate cancer. A 17-gene expression signature (Genomic Prostate Score [GPS]), previously validated to predict aggressive prostate cancer when measured in tumor tissue, was also assessed using pre-specified genes and algorithms. Analysis used Cox proportional hazards models, Storey's false discovery rate (FDR) control, and regression to the mean (RM) correction. Conclusions Gene expression profiles, including GPS, from NT adjacent to tumor can predict prostate cancer outcome. These findings suggest that there is a biologically significant field effect in primary prostate cancer that is a marker for aggressive disease. PMID:27121323

  4. Expression and significance of 90K/Mac-2BP in prostate cancer.

    PubMed

    Hu, Jianxin; He, Jian; Kuang, Youlin; Wang, Zhenxing; Sun, Zhaolin; Zhu, Hengcheng; Liu, Xiuheng

    2013-01-01

    The aim of this study was to detect the differences in 90K/Mac-2BP expression in prostate cancer, benign prostatic hyperplasia and normal prostate tissues, as well as to study the significance of 90K/Mac-2BP in the early diagnosis and prognosis of prostate cancer. Comparative proteomic technologies were used in the present study. Total protein from 10 cases of prostate cancer, benign prostatic hyperplasia and normal prostate tissue was extracted and separated by two-dimensional electrophoresis (2-DE). Proteins expressed differentially by more than 2-fold were selected for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) and biological information analysis. The 2-DE patterns of the proteins from the normal prostate, benign prostatic hyperplasia and prostate cancer tissues were successfully identified. The average numbers of protein spots were 3,066, 3,289 and 2,986, respectively. There were 31 spots with a difference of more than 2-fold. A total of 18 proteins were identified by MS and database searches. Of these 18 proteins, the most significant differential expression was that of 90K/Mac-2BP. Functional analysis demonstrated that 90K/Mac-2BP (Mac-2 binding protein) overexpression is correlated with the occurrence, proliferation, differentiation and metastasis of cancer cells. The proteomic approach used in the present study was effective and is feasible for identifying differentially expressed proteins in prostate cancer, benign prostatic hyperplasia and normal prostate tissues. 90K/Mac-2BP may be important for the early diagnosis and prognosis of prostate cancer and may also be associated with the molecular mechanisms of prostate cancer development.

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

    ClinicalTrials.gov

    2016-06-17

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

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

    PubMed Central

    Ayyıldız, Sema Nur; Ayyıldız, Ali

    2014-01-01

    Currently, prostate- specific antigen (PSA) is the most common oncological marker used for prostate cancer screening. However, high levels of PSA in benign prostatic hyperplasia and prostatitis decrease the specificity of PSA as a cancer marker. To increase the specificity of PSA, PSA derivatives and PSA kinetics have been used. However, these new techniques were not able to increase the diagnostic specificity for prostate cancer. Therefore, the search for new molecules and derivatives of PSA continues. With the aim of increasing the specificity of prostate cancer diagnosis, proPSA and the Prostate Health Index have been introduced. In this review, the roles of PSA, PSA derivatives, proPSA and the Prostate Health Index in Prostate Cancer diagnosis are examined. PMID:26328156

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

    PubMed Central

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

    2014-01-01

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

  8. Cholesterol Metabolism and Prostate Cancer Lethality.

    PubMed

    Stopsack, Konrad H; Gerke, Travis A; Sinnott, Jennifer A; Penney, Kathryn L; Tyekucheva, Svitlana; Sesso, Howard D; Andersson, Swen-Olof; Andrén, Ove; Cerhan, James R; Giovannucci, Edward L; Mucci, Lorelei A; Rider, Jennifer R

    2016-08-15

    Cholesterol metabolism has been implicated in prostate cancer pathogenesis. Here, we assessed the association of intratumoral mRNA expression of cholesterol synthesis enzymes, transporters, and regulators in tumor specimen at diagnosis and lethal prostate cancer, defined as mortality or metastases from prostate cancer in contrast to nonlethal disease without evidence of metastases after at least 8 years of follow-up. We analyzed the prospective prostate cancer cohorts within the Health Professionals Follow-up Study (n = 249) and the Physicians' Health Study (n = 153) as well as expectantly managed patients in the Swedish Watchful Waiting Study (n = 338). The expression of squalene monooxygenase (SQLE) was associated with lethal cancer in all three cohorts. Men with high SQLE expression (>1 standard deviation above the mean) were 8.3 times (95% confidence interval, 3.5 to 19.7) more likely to have lethal cancer despite therapy compared with men with the mean level of SQLE expression. Absolute SQLE expression was associated with lethal cancer independently from Gleason grade and stage, as was a SQLE expression ratio in tumor versus surrounding benign prostate tissue. Higher SQLE expression was tightly associated with increased histologic markers of angiogenesis. Collectively, this study establishes the prognostic value of intratumoral cholesterol synthesis as measured via SQLE, its second rate-limiting enzyme. SQLE expression at cancer diagnosis is prognostic for lethal prostate cancer both after curative-intent prostatectomy and in a watchful waiting setting, possibly by facilitating micrometastatic disease. Cancer Res; 76(16); 4785-90. ©2016 AACR.

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

    PubMed

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

    2016-08-15

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

  10. Protective effect of carboxymethyl-glucan (CM-G) against DNA damage in patients with advanced prostate cancer.

    PubMed

    Magnani, Marciane; Castro-Gomez, Raul Jorge Hernan; Mori, Mateus Prates; Kuasne, Hellen; Gregório, Emerson Pereira; Libos, Farid; de Syllos Cólus, Ilce Mara

    2011-01-01

    Carboxymethyl-glucan (CM-G) is a soluble derivative from Saccharomyces cerevisiae (1 → 3)(1 → 6)-β-D-glucan. The protective efficiency of CM-G against DNA damage in cells from patients with advanced prostate cancer (PCa), and undergoing Androgen Deprivation Therapy (ADT), was evaluated. DNA damage scores were obtained by the comet assay, both before and after treatment with CM-G. The reduction in DNA damage, ranging from 18% to 87%, with an average of 59%, was not related to the increased number of leukocytes in peripheral blood. The results demonstrate for the first time the protective effect of CM-G against DNA damage in patients with advanced PCa. Among smokers, three presented the highest reduction in DNA damage after treatment with CM-G. There was no observable relationship between DNA damage scores before and after treatment, and age, alcoholism and radiotherapy.

  11. Protective effect of carboxymethyl-glucan (CM-G) against DNA damage in patients with advanced prostate cancer

    PubMed Central

    Magnani, Marciane; Castro-Gomez, Raul Jorge Hernan; Mori, Mateus Prates; Kuasne, Hellen; Gregório, Emerson Pereira; Libos, Farid; de Syllos Cólus, Ilce Mara

    2011-01-01

    Carboxymethyl-glucan (CM-G) is a soluble derivative from Saccharomyces cerevisiae (1 → 3)(1 → 6)-β-D-glucan. The protective efficiency of CM-G against DNA damage in cells from patients with advanced prostate cancer (PCa), and undergoing Androgen Deprivation Therapy (ADT), was evaluated. DNA damage scores were obtained by the comet assay, both before and after treatment with CM-G. The reduction in DNA damage, ranging from 18% to 87%, with an average of 59%, was not related to the increased number of leukocytes in peripheral blood. The results demonstrate for the first time the protective effect of CM-G against DNA damage in patients with advanced PCa. Among smokers, three presented the highest reduction in DNA damage after treatment with CM-G. There was no observable relationship between DNA damage scores before and after treatment, and age, alcoholism and radiotherapy. PMID:21637556

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

    PubMed

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

    2016-08-15

    Multicellular tumour spheroids (MTS) are three-dimensional cell cultures that possess their own microenvironments and provide a more meaningful model of tumour biology than monolayer cultures. As a result, MTS are becoming increasingly used as tumor models when measuring the efficiency of therapies. Monitoring the viability of live MTS is complicated by their 3D nature and conventional approaches such as fluorescence often require fixation and sectioning. In this paper we detail the use of Surface Enhanced Raman Spectroscopy (SERS) to measure the viability of MTS grown from prostate cancer (PC3) cells. Our results show that we can monitor loss of viability by measuring pH and redox potential in MTS and furthermore we demonstrate that SERS can be used to measure the effects of fractionation of a dose of radiotherapy in a way that has potential to inform treatment planning. PMID:27310732

  13. The level of knowledge and awareness about prostate cancer in the Turkish male and the relevant effective factors

    PubMed Central

    Turkan, Sadi; Doğan, Faruk; Ekmekçioğlu, Ozan; Çolak, Aslıhan; Kalkan, Mehmet; Şahin, Çoşkun

    2016-01-01

    Objective Our aim was to determine the general knowledge and awareness levels, information sources, and the state of medical check-up for prostate cancer (PCa) and relevant effective factors. Material and methods The participants were asked to answer to 14 questions of a questionnaire about age, education, economic and social condition, knowledge about PCa, state of being examined and their related factors. According to demographic characteristics of the participants, levels of awareness about PCa, sources of information, affecting factors and their interrelationships were examined. Two groups were formed according to age (<60 years, >60 years) and variations according to ages were investigated. Results Two hundred and ninety-three men with an average age of 57 years (range 40–85) were included in the study. Our findings showed that 68.3% of the participants were thinking that PCa is a frequently seen disease, 88.4% were thinking that it can be treated and 62.8% of men specified that their information sources are doctors. We also found that 60.8% of the participants had not undergone prostate examination and prostate specific antigen (PSA) control. The most reason for not having annual examinations was (44.4%) “negligence”. Significantly greater number of men with higher education (high school/university) were highly informed about PCa (p=0.037). Check-up rates were statistically significantly higher among men with intermediate income (p=0.041). Curability of PCa diagnosed at an early stage was acknowledged by statistically higher number of individuals under the age 60 (p<0.05). Health control, prostate examination and/or PSA control rates were higher in men with a family history of PCa and in the group of >60 years. Conclusion Although PCa has a high prevalence and mortality rates, personal and social information and sensitivity levels must be increased as it can be treated if diagnosed at an early stage. We think that social and medical impact of the

  14. The level of knowledge and awareness about prostate cancer in the Turkish male and the relevant effective factors

    PubMed Central

    Turkan, Sadi; Doğan, Faruk; Ekmekçioğlu, Ozan; Çolak, Aslıhan; Kalkan, Mehmet; Şahin, Çoşkun

    2016-01-01

    Objective Our aim was to determine the general knowledge and awareness levels, information sources, and the state of medical check-up for prostate cancer (PCa) and relevant effective factors. Material and methods The participants were asked to answer to 14 questions of a questionnaire about age, education, economic and social condition, knowledge about PCa, state of being examined and their related factors. According to demographic characteristics of the participants, levels of awareness about PCa, sources of information, affecting factors and their interrelationships were examined. Two groups were formed according to age (<60 years, >60 years) and variations according to ages were investigated. Results Two hundred and ninety-three men with an average age of 57 years (range 40–85) were included in the study. Our findings showed that 68.3% of the participants were thinking that PCa is a frequently seen disease, 88.4% were thinking that it can be treated and 62.8% of men specified that their information sources are doctors. We also found that 60.8% of the participants had not undergone prostate examination and prostate specific antigen (PSA) control. The most reason for not having annual examinations was (44.4%) “negligence”. Significantly greater number of men with higher education (high school/university) were highly informed about PCa (p=0.037). Check-up rates were statistically significantly higher among men with intermediate income (p=0.041). Curability of PCa diagnosed at an early stage was acknowledged by statistically higher number of individuals under the age 60 (p<0.05). Health control, prostate examination and/or PSA control rates were higher in men with a family history of PCa and in the group of >60 years. Conclusion Although PCa has a high prevalence and mortality rates, personal and social information and sensitivity levels must be increased as it can be treated if diagnosed at an early stage. We think that social and medical impact of the

  15. Breast and Prostate Cancer Cohort Consortium (BPC3)

    Cancer.gov

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

  16. Piezoelectricity and prostate cancer: proposed interaction between electromagnetic field and prostatic crystalloids.

    PubMed

    Ghabili, Kamyar; Shoja, Mohammadali M; Agutter, Paul S

    2008-06-01

    There is evidence that electromagnetic fields (EMF) play some part in the pathogenesis of prostate cancer, but the pathogenic mechanism remains unknown. The normal prostate gland and both benign and malignant prostate lesions contain abundant calcium/phosphorus crystalloids with various morphologies, which seem to be heterogeneously and diffusely distributed within the gland. We hypothesize that an environmental EMF may result in simultaneous, multidirectional and diffuse compression or expansion of these crystalloids (a piezoelectric effect). This would result in a slight mechanical distortion of the prostate, potentially altering cell behavior and enhancing the expression of specific genes, particularly those involved in suppressing apoptosis. A mathematical model of the cell mechanical effect is presented, and the hypothesis is related to current clinical evidence and to potential validation by critical laboratory tests.

  17. Heme oxygenase-1 in macrophages controls prostate cancer progression

    PubMed Central

    Nemeth, Zsuzsanna; Li, Mailin; Csizmadia, Eva; Döme, Balazs; Johansson, Martin; Persson, Jenny Liao; Seth, Pankaj; Otterbein, Leo; Wegiel, Barbara

    2015-01-01

    Innate immune cells strongly influence cancer growth and progression via multiple mechanisms including regulation of epithelial to mesenchymal transition (EMT). In this study, we investigated whether expression of the metabolic gene, heme oxygenase-1 (HO-1) in tumor microenvironment imparts significant effects on prostate cancer progression. We showed that HO-1 is expressed in MARCO-positive macrophages in prostate cancer (PCa) xenografts and human prostate cancers. We demonstrated that macrophage specific (LyzM-Cre) conditional deletion of HO-1 suppressed growth of PC3 xenografts in vivo and delayed progression of prostate intraepithelial neoplasia (PIN) in TRAMP mice. However, initiation and progression of cancer xenografts in the presence of macrophages lacking HO-1 resulted in loss of E-cadherin, a known marker of poor prognosis as well as EMT. Application of CO, a product of HO-1 catalysis, increased levels of E-cadherin in the adherens junctions between cancer cells. We further showed that HO-1-driven expression of E-cadherin in cancer cells cultured in the presence of macrophages is dependent on mitochondrial activity of cancer cells. In summary, these data suggest that HO-1-derived CO from tumor-associated macrophages influences, in part, E-cadherin expression and thus tumor initiation and progression. PMID:26418896

  18. MET expression during prostate cancer progression

    PubMed Central

    Verhoef, Esther I.; van der Steen, Berdine; Hoogland, A. Marije; Sleddens, Hein F.B.M.; Looijenga, Leendert H.J.; van Leenders, Geert J.L.H.

    2016-01-01

    Tyrosine-kinase inhibitors of the hepatocyte growth factor receptor MET are under investigation for the treatment of hormone-refractory prostate cancer (HRPC) metastasis. Analysis of MET protein expression and genetic alterations might contribute to therapeutic stratification of prostate cancer patients. Our objective was to investigate MET on protein, DNA and RNA level in clinical prostate cancer at various stages of progression. Expression of MET was analyzed in hormone-naive primary prostate cancers (N=481), lymph node (N=40) and bone (N=8) metastases, as well as HRPC (N=54) and bone metastases (N=15). MET protein expression was analyzed by immunohistochemistry (D1C2 C-terminal antibody). MET mRNA levels and MET DNA copy numbers were determined by in situ hybridization. None of the hormone-naive primary prostate cancer or lymph node metastases demonstrated MET protein or mRNA expression. In contrast, MET protein was expressed in 12/52 (23%) evaluable HRPC resections. RNA in situ demonstrated cytoplasmic signals in 14/54 (26%) of the HRPC patients, and was associated with MET protein expression (p=0.025, χ2), in absence of MET amplification or polysomy. MET protein expression was present in 7/8 (88%) hormone-naive and 10/15 (67%) HRPC bone metastases, without association of HRPC (p=0.37; χ2), with MET polysomy in 8/13 (61%) evaluable cases. In conclusion, MET was almost exclusively expressed in HRPC and prostate cancer bone metastasis, but was not related to MET amplification or polysomy. Evaluation of MET status could be relevant for therapeutic stratification of late stage prostate cancer. PMID:27105539

  19. Prostate cancer epigenetics and its clinical implications

    PubMed Central

    Yegnasubramanian, Srinivasan

    2016-01-01

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

  20. Extremely Early Diagnostic Test for Prostate Cancer

    SciTech Connect

    James, Veronica Jean

    2011-11-17

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

  1. Prostate cancer radiation therapy: A physician's perspective.

    PubMed

    Dal Pra, Alan; Souhami, Luis

    2016-03-01

    Prostate cancer is the second most common cancer in men and a major cause of cancer deaths worldwide. Ionizing radiation has played a substantial role in the curative treatment of this disease. The historical evolution of radiotherapy techniques through 3D-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and image-guided radiotherapy (IGRT) has allowed more accurate and precise treatments toward significant improvements in the therapeutic ratio. The addition of androgen deprivation therapy has significantly improved overall survival becoming the standard therapy for intermediate- and high-risk disease. Many randomized controlled trials have shown improved local control with dose escalation, and hypofractionated RT has been consolidated with proven efficacy and safe clinical results. However, several questions remain open in the radiotherapeutic management of prostate cancer patients and hopefully ongoing studies will shed light on these uncertainties. More individualized approaches are essential through better prognostic and novel predictive biomarkers of prostate radiotherapy response. Clinicians should critically interpret the evolving technologies in prostate cancer radiotherapy with important optimism but balancing the costs and the actual magnitude of clinical benefit. This article provides an overview of the basic aspects of radiotherapy treatment in localized prostate cancer from a physician's perspective. PMID:27056435

  2. External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

    SciTech Connect

    Cho, Eunpi; Mostaghel, Elahe A.; Russell, Kenneth J.; Liao, Jay J.; Konodi, Mark A.; Kurland, Brenda F.; Marck, Brett T.; Matsumoto, Alvin M.; Dalkin, Bruce L.; Montgomery, R. Bruce

    2015-06-01

    Purpose: Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. Methods and Materials: A prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at the discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. Results: A total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse. Conclusions: Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression

  3. How surgical innovation reduced death and suffering from prostate cancer.

    PubMed

    Walsh, Patrick C

    2013-01-01

    Radical prostatectomy for the cure of prostate cancer never gained widespread popularity because of severe side effects: all men were impotent, many were totally incontinent, and when performed by the retropubic approach, bleeding was often life threatening. When I arrived at Johns Hopkins in 1974 as the new director of the Brady Urological Institute, I embarked upon a series of anatomic studies to determine the source of this morbidity. Using the operating room as an anatomy laboratory and performing dissections in stillborn male infants, it was possible to define important, previously unrecognized anatomic structures. Application of these discoveries to the surgical technique made it possible to preserve sexual function, reduce urinary continence to a minimum, and perform the procedure in a relative bloodless field. Armed with the ability to cure prostate cancer more safely with surgery and with fewer side effects, radical prostatectomy was rapidly adopted and in the following decade death from prostate cancer declined by 40%.

  4. Image-guided focal therapy for prostate cancer

    PubMed Central

    Sankineni, Sandeep; Wood, Bradford J.; Rais-Bahrami, Soroush; Diaz, Annerleim Walton; Hoang, Anthony N.; Pinto, Peter A.; Choyke, Peter L.; Türkbey, Barış

    2014-01-01

    The adoption of routine prostate specific antigen screening has led to the discovery of many small and low-grade prostate cancers which have a low probability of causing mortality. These cancers, however, are often treated with radical therapies resulting in long-term side effects. There has been increasing interest in minimally invasive focal therapies to treat these tumors. While imaging modalities have improved rapidly over the past decade, similar advances in image-guided therapy are now starting to emerge—potentially achieving equivalent oncologic efficacy while avoiding the side effects of conventional radical surgery. The purpose of this article is to review the existing literature regarding the basis of various focal therapy techniques such as cryotherapy, microwave, laser, and high intensity focused ultrasound, and to discuss the results of recent clinical trials that demonstrate early outcomes in patients with prostate cancer. PMID:25205025

  5. Geographical epidemiology of prostate cancer in Great Britain.

    PubMed

    Jarup, Lars; Best, Nicky; Toledano, Mireille B; Wakefield, Jon; Elliott, Paul

    2002-02-10

    Prostate cancer incidence has increased during recent years, possibly linked to environmental exposures. Exposure to environmental carcinogens is unlikely to be evenly distributed geographically, which may give rise to variations in disease occurrence that is detectable in a spatial analysis. The aim of our study was to examine the spatial variation of prostate cancer in Great Britain at ages 45-64 years. Spatial variation was examined across electoral wards from 1975-1991. Poisson regression was used to examine regional, urbanisation and socioeconomic effects, while Bayesian mapping techniques were used to assess spatial variability. There was an indication of geographical differences in prostate cancer risk at a regional level, ranging from 0.83 (95% CI: 0.78-0.87) to 1.2 (95% CI: 1.1-1.3) across regions. There was significant heterogeneity in the risk across wards, although the range of relative risks was narrow. More detailed spatial analyses within 4 regions did not indicate any clear evidence of localised geographical clustering for prostate cancer. The absence of any marked geographical variability at a small-area scale argues against a geographically varying environmental factor operating strongly in the aetiology of prostate cancer. PMID:11807800

  6. Geographical epidemiology of prostate cancer in Great Britain.

    PubMed

    Jarup, Lars; Best, Nicky; Toledano, Mireille B; Wakefield, Jon; Elliott, Paul

    2002-02-10

    Prostate cancer incidence has increased during recent years, possibly linked to environmental exposures. Exposure to environmental carcinogens is unlikely to be evenly distributed geographically, which may give rise to variations in disease occurrence that is detectable in a spatial analysis. The aim of our study was to examine the spatial variation of prostate cancer in Great Britain at ages 45-64 years. Spatial variation was examined across electoral wards from 1975-1991. Poisson regression was used to examine regional, urbanisation and socioeconomic effects, while Bayesian mapping techniques were used to assess spatial variability. There was an indication of geographical differences in prostate cancer risk at a regional level, ranging from 0.83 (95% CI: 0.78-0.87) to 1.2 (95% CI: 1.1-1.3) across regions. There was significant heterogeneity in the risk across wards, although the range of relative risks was narrow. More detailed spatial analyses within 4 regions did not indicate any clear evidence of localised geographical clustering for prostate cancer. The absence of any marked geographical variability at a small-area scale argues against a geographically varying environmental factor operating strongly in the aetiology of prostate cancer.

  7. [Staging Based Strategies and Practice for Prostate Cancer].

    PubMed

    Chen, Zhi-qiang; Wang, Shu-sheng; Bai, Zun-guang; Wang, Zhao-hui; Lv, Li-guo; Gu, Chi-ming; Xiang, Song-tao; Dai, Rui-xin; Zhu, Shou-lun

    2016-06-01

    Authors raised that staging based strategies and practice of integrative medicine (IM) by combining syndrome typing and disease identification, and choosing suitable measures in accordance with different persons and seasonal conditions after more than ten years' clinical practice and researches. Radical operation as prior (as evil eliminating) and strengthening vital qi in perioerative period are best strategy for promoting rapid rehabilitation of early stage prostate cancer patients. Strengthening body resistance to eliminate evil was used in treating advanced prostate cancer patients. For example, a comprehensive treatment program for hormone-dependent patients was combined with endocrinotherapy and Chinese herbs for synergisic efficacy-enhancing actions. In this way, these patients' quality of life (QOL) were improved and time to castration resistant prostate cancer (CRPC) was delayed, even some patients were clinically cured. There are lack of effective medicines and methods for CRPC patients. Greatly tonifying original qi is mainly used for improving their clinical symptoms and prolonging survivals. Practice has proved staging based strategies and practice of IM has favorable advantages in treating prostate cancer, especially showing prospect in prolonging survival and postponing progression of advanced prostate cancer patients. Besides, it also could provide beneficial considerations and inspiration for combination of syndrome typing and disease identification. PMID:27491237

  8. Geranylated 4-Phenylcoumarins Exhibit Anticancer Effects against Human Prostate Cancer Cells through Caspase-Independent Mechanism

    PubMed Central

    Suparji, Noor Shahirah; Chan, Gomathi; Sapili, Hani; Arshad, Norhafiza M.; In, Lionel L. A.; Awang, Khalijah; Hasima Nagoor, Noor

    2016-01-01

    Geranylated 4-phenylcoumarins, DMDP-1 & -2 isolated from Mesua elegans were investigated for anticancer potential against human prostate cancer cells. Treatment with DMDP-1 & -2 resulted in cell death in a time and dose dependent manner in an MTT assay on all cancer cell lines tested with the exception of lung adenocarcinoma cells. DMDP-1 showed highest cytotoxic efficacy in PC-3 cells while DMDP-2 was most potent in DU 145 cells. Flow cytometry indicated that both coumarins were successful to induce programmed cell death after 24 h treatment. Elucidation on the mode-of-action via protein arrays and western blotting demonstrated death induced without any significant expressions of caspases, Bcl-2 family proteins and cleaved PARP, thus suggesting the involvement of caspase-independent pathways. In identifying autophagy, analysis of GFP-LC3 showed increased punctate in PC-3 cells pre-treated with CQ and treated with DMDP-1. In these cells decreased expression of autophagosome protein, p62 and cathepsin B further confirmed autophagy. In contrary, the DU 145 cells pre-treated with CQ and treated with DMDP-2 has reduced GFP-LC3 punctate although the number of cells with obvious GFP-LC3 puncta was significantly increased in the inhibitor-treated cells. The increase level of p62 suggested leakage of cathepsin B into the cytosol to trigger potential downstream death mediators. This correlated with increased expression of cathepsin B and reduced expression after treatment with its inhibitor, CA074. Also auto-degradation of calpain-2 upon treatment with DMDP-1 &-2 and its inhibitor alone, calpeptin compared with the combination treatment, further confirmed involvement of calpain-2 in PC-3 and DU 145 cells. Treatment with DMDP-1 & -2 also showed up-regulation of total and phosphorylated p53 levels in a time dependent manner. Hence, DMDP-1 & -2 showed ability to activate multiple death pathways involving autophagy, lysosomal and endoplasmic reticulum death proteins which could

  9. Development of PROSTVAC immunotherapy in prostate cancer

    PubMed Central

    Singh, Parminder; Pal, Sumanta K; Alex, Anitha; Agarwal, Neeraj

    2015-01-01

    PROSTVAC immunotherapy is a heterologous prime-boost regimen of two different recombinant pox-virus vectors; vaccinia as the primary immunotherapy, followed by boosters employing fowlpox, to provoke immune responses against prostate-specific antigen. Both vectors contain transgenes for prostate-specific antigen and a triad of T-cell costimulatory molecules (TRICOM). In a placebo-controlled Phase II trial of men with minimally symptomatic, chemotherapy-naive metastatic castration-resistant prostate cancer, PROSTVAC was well tolerated and associated with a 44% reduction in death. With a novel mechanism of action, and excellent tolerability, PROSTVAC has the potential to dramatically alter the treatment landscape of prostate cancer, not only as a monotherapy, but also in combination with other novel agents, such as immune check point inhibitors and novel androgen receptor blockers. A Phase III trial recently completed accrual. PMID:26235179

  10. Risk stratification of prostate cancer 2016.

    PubMed

    Reiter, Robert E

    2016-01-01

    Prostate cancer is a common malignancy in men, but its management is fraught with controversy owing to its variable biologic and clinical behavior. Despite evidence that PSA screening reduces prostate cancer specific metastasis and death, it has not gained acceptance by various health authorities. Nevertheless, recent advances in biomarker development potentially address many of the shortcomings of routine PSA testing alone, including improved specificity for the detection of clinically significant cancer, optimized risk stratification to aid clinical management decisions, and discovery of genetic variants that may guide optimized therapy of advanced disease. PMID:27533326

  11. Antiproliferative effect on human prostate cancer cells by a stinging nettle root (Urtica dioica) extract.

    PubMed

    Konrad, L; Müller, H H; Lenz, C; Laubinger, H; Aumüller, G; Lichius, J J

    2000-02-01

    In the present study the activity of a 20% methanolic extract of stinging nettle roots (Urtica dioica L., Urticaceae) on the proliferative activity of human prostatic epithelial (LNCaP) and stromal (hPCPs) cells was evaluated using a colorimetric assay. A concentration-dependent and significant (p < 0.05) antiproliferative effect of the extract was observed only on LNCaP cells during 7 days, whereas stromal cell growth remained unaltered. The inhibition was time-dependent with the maximum of growth reduction (30%) at a concentration of 1.0E-6 mg/ml on day 5 compared to the untreated control. On day 4 and 6, the reduction in proliferation of LNCaP cells showed the minimal effective dose at 1.0E-9 mg/ml. No cytotoxic effect of ME-20 on cell proliferation was observed. The antiproliferative effect of ME-20 of stinging nettle roots observed both in an in vivo model and in an in vitro system clearly indicates a biologically relevant effect of compounds present in the extract. PMID:10705733

  12. Prostatic and dietary omega-3 fatty acids and prostate cancer progression during active surveillance.

    PubMed

    Moreel, Xavier; Allaire, Janie; Léger, Caroline; Caron, André; Labonté, Marie-Ève; Lamarche, Benoît; Julien, Pierre; Desmeules, Patrice; Têtu, Bernard; Fradet, Vincent

    2014-07-01

    The association between omega-3 (ω-3) fatty acids and prostate cancer has been widely studied. However, little is known about the impact of prostate tissue fatty acid content on prostate cancer progression. We hypothesized that compared with the estimated dietary ω-3 fatty acids intake and the ω-3 fatty acids levels measured in red blood cells (RBC), the prostate tissue ω-3 fatty acid content is more strongly related to prostate cancer progression. We present the initial observations from baseline data of a phase II clinical trial conducted in a cohort of 48 untreated men affected with low-risk prostate cancer, managed under active surveillance. These men underwent a first repeat biopsy session within 6 months after the initial diagnosis of low-risk prostate cancer, at which time 29% of the men had progressed from a Gleason score of 6 to a Gleason score of 7. At the first repeat biopsy session, fatty acid levels were assessed with a food-frequency questionnaire, and determined in the RBC and in the prostate tissue biopsy. We found that eicosapentaenoic acid (EPA) was associated with a reduced risk of prostate cancer progression when measured directly in the prostate tissue. Thus, this initial interim study analysis suggests that prostate tissue ω-3 fatty acids, especially EPA, may be protective against prostate cancer progression in men with low-risk prostate cancer.

  13. The effect of statins on prostate cancer recurrence and mortality after definitive therapy: a systematic review and meta-analysis

    PubMed Central

    Tan, Ping; Wei, Shiyou; Yang, Lu; Tang, Zhuang; Cao, Dehong; Liu, Liangren; Lei, Junhao; Fan, Yu; Gao, Liang; Wei, Qiang

    2016-01-01

    In this work, we aim to further analyze the association of statins use with biochemical recurrence (BCR) of prostate cancer (PCa) and PCa-specific mortality after definitive therapy. A systematic literature search of PubMed, MEDLINE, and EMBASE through Jul 2015 was conducted. Pooled Hazard ratio (HR) estimates with corresponding 95% confidence intervals (CIs) were calculated using random-effects model. STATA version 10 (Stata corporation, college station, TX) was employed to conduct all statistical analyses. A total of 22 and 8 studies contributed to the biochemical recurrence analysis and PCa-specific mortality, respectively. 13 trials were included for BCR-free survival analysis. The combined result showed statins users had lowered 12% BCR risk of PCa compared with non-users (HR = 0.88, 95%CI: 0.765–0.998) (p < 0.05). The association was null among the men who underwent radical prostatectomy as primary therapy (HR = 0.96, 95%CI: 0.83–1.09), while the improved outcomes had be seen among patients who received radiation therapy (HR = 0.67, 95%CI: 0.48–0.86). After excluding the patients undergoing ADT, participants did not benefit from statins use (HR = 0.94, 95%CI: 0.77–1.11). Meanwhile, long-term statins using did not alter recurrence risk. A lower risk of prostate cancer-specific mortality was observed among statins users (HR = 0.68, 95%CI: 0.56–0.80). There was a plausible trend towards increasing the BCR-free survival rate among statins users. PMID:27384548

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

    NASA Astrophysics Data System (ADS)

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

    2011-11-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

  16. Selenium Supplementation and Prostate Cancer Mortality

    PubMed Central

    Van Blarigan, Erin L.; DuPre, Natalie; Stampfer, Meir J.; L. Giovannucci, Edward; Chan, June M.

    2015-01-01

    Background: Few studies have evaluated the relation between selenium supplementation after diagnosis and prostate cancer outcomes. Methods: We prospectively followed 4459 men initially diagnosed with nonmetastatic prostate cancer in the Health Professionals Follow-Up Study from 1988 through 2010 and examined whether selenium supplement use (from selenium-specific supplements and multivitamins) after diagnosis was associated with risk of biochemical recurrence, prostate cancer mortality, and, secondarily, cardiovascular disease mortality and overall mortality, using Cox proportional hazards models. All P values were from two-sided tests. Results: We documented 965 deaths, 226 (23.4%) because of prostate cancer and 267 (27.7%) because of cardiovascular disease, during a median follow-up of 8.9 years. In the biochemical recurrence analysis, we documented 762 recurrences during a median follow-up of 7.8 years. Crude rates per 1000 person-years for prostate cancer death were 5.6 among selenium nonusers and 10.5 among men who consumed 140 or more μg/day. Crude rates per 1000 person-years were 28.2 vs 23.5 for all-cause mortality and 28.4 vs 29.3 for biochemical recurrence, for nonuse vs highest-dose categories, respectively. In multivariable analyses, men who consumed 1 to 24 μg/day, 25 to 139 μg/day, and 140 or more μg/day of supplemental selenium had a 1.18 (95% confidence interval [CI] = 0.73 to 1.91), 1.33 (95% CI = 0.77 to 2.30), and 2.60-fold (95% CI = 1.44 to 4.70) greater risk of prostate cancer mortality compared with nonusers, respectively, P trend = .001. There was no statistically significant association between selenium supplement use and biochemical recurrence, cardiovascular disease mortality, or overall mortality. Conclusion: Selenium supplementation of 140 or more μg/day after diagnosis of nonmetastatic prostate cancer may increase risk of prostate cancer mortality. Caution is warranted regarding usage of such supplements among men with prostate

  17. Carr-Purcell-Meiboom-Gill imaging of prostate cancer: quantitative T2 values for cancer discrimination.

    PubMed

    Roebuck, Joseph R; Haker, Steven J; Mitsouras, Dimitris; Rybicki, Frank J; Tempany, Clare M; Mulkern, Robert V

    2009-05-01

    Quantitative, apparent T(2) values of suspected prostate cancer and healthy peripheral zone tissue in men with prostate cancer were measured using a Carr-Purcell-Meiboom-Gill (CPMG) imaging sequence in order to assess the cancer discrimination potential of tissue T(2) values. The CPMG imaging sequence was used to image the prostates of 18 men with biopsy-proven prostate cancer. Whole gland coverage with nominal voxel volumes of 0.54 x 1.1 x 4 mm(3) was obtained in 10.7 min, resulting in data sets suitable for generating high-quality images with variable T(2)-weighting and for evaluating quantitative T(2) values on a pixel-by-pixel basis. Region-of-interest analysis of suspected healthy peripheral zone tissue and suspected cancer, identified on the basis of both T(1)- and T(2)-weighted signal intensities and available histopathology reports, yielded significantly (P<.0001) longer apparent T(2) values in suspected healthy tissue (193+/-49 ms) vs. suspected cancer (100+/-26 ms), suggesting potential utility of this method as a tissue specific discrimination index for prostate cancer. We conclude that CPMG imaging of the prostate can be performed in reasonable scan times and can provide advantages over T(2)-weighted fast spin echo (FSE) imaging alone, including quantitative T(2) values for cancer discrimination as well as proton density maps without the point spread function degradation associated with short effective echo time FSE sequences. PMID:18823731

  18. [EPCA-2 in the early diagnosis of prostate cancer].

    PubMed

    Yu, De-Shui; Xu, Zhuo-Qun

    2010-06-01

    More and more clinical evidence has confirmed the limitations of the use of serum PSA in the screening, detection and treatment of prostate cancer, and scientists are continuously seeking for new biomarkers of the disease. The discovery of early prostate cancer antigen 2 (EPCA-2) has provided a new base for the screening, detection, treatment and follow-up of prostate cancer.

  19. 76 FR 55551 - National Prostate Cancer Awareness Month, 2011

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-07

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

  20. Studying depletion kinetics of circulating prostate cancer cells by in vivo flow cytometer

    NASA Astrophysics Data System (ADS)

    Liu, Guangda; Gu, Zhengqin; Guo, Jin; Li, Yan; Chen, Yun; Chen, Tong; Wang, Cheng; Wei, Xunbin

    2011-03-01

    Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. During this time, the tumor produces little or no symptoms or outward signs. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal near-infrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. A real- time quantitative monitoring of circulating prostate cancer cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential therapeutic interventions.

  1. Depletion kinetics of circulating prostate cancer cells studied by in vivo flow cytometer

    NASA Astrophysics Data System (ADS)

    Liu, Guangda; Guo, Jin; Li, Yan; Chen, Yun; Gu, Zhengqin; Chen, Tong; Wang, Cheng; Wei, Xunbin

    2010-11-01

    Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. During this time, the tumor produces little or no symptoms or outward signs. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal nearinfrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. A real- time quantitative monitoring of circulating prostate cancer cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential therapeutic interventions.

  2. Testosterone and prostate cancer: an evidence-based review of pathogenesis and oncologic risk.

    PubMed

    Michaud, Jason E; Billups, Kevin L; Partin, Alan W

    2015-12-01

    Testosterone plays a central role in male development and health. Likewise, androgen deficiency, or hypogonadism, is associated with a variety of symptoms including decreased energy, diminished libido and erectile dysfunction, among others. Male androgen levels steadily decline with age, and, in a subset of symptomatic older men, can result in late-onset hypogonadism (LOH). Over the last decade, increased awareness of hypogonadism among patients and providers has led to a significant rise in the use of testosterone replacement therapy (TRT) for hypogonadism, and especially in LOH. Accompanying the rise in TRT are concerns of potential adverse effects, including cardiovascular risks and the promotion of prostate cancer. The 'androgen hypothesis' asserts that prostate cancer development and progression is driven by androgens, and thus TRT has the theoretical potential to drive prostate cancer development and progression. In this review, we examine existing data surrounding testosterone and prostate cancer. There is significant evidence that androgens promote prostate cancer in experimental systems. However, there is no clear evidence that elevations in endogenous testosterone levels promote the development of prostate cancer in humans. As a result of experimental and historical data on the progression of prostate cancer following TRT, there has been widespread belief that TRT will promote disease progression in prostate cancer patients. Despite these fears, there are a growing number of studies demonstrating no increase in prostate cancer incidence among men on TRT. Furthermore, in studies involving a small number of patients, there has been no discernable increase in disease progression in prostate cancer patients on TRT. While data from large, prospective, randomized, controlled trials are absent, TRT in select prostate cancer patients is likely safe. In the end, the use of TRT in prostate cancer patients is still considered experimental and should only be offered

  3. Fine-mapping IGF1 and prostate cancer risk in African Americans: the multiethnic cohort study.

    PubMed

    Giorgi, Elena E; Stram, Daniel O; Taverna, Darin; Turner, Stephen D; Schumacher, Fredrick; Haiman, Christopher A; Lum-Jones, Annette; Tirikainen, Maarit; Caberto, Christian; Duggan, David; Henderson, Brian E; Le Marchand, Loic; Cheng, Iona

    2014-09-01

    Genetic variation at insulin-like growth factor 1 (IGF1) has been linked to prostate cancer risk. However, the specific predisposing variants have not been identified. In this study, we fine-mapped the IGF1 locus for prostate cancer risk in African Americans. We conducted targeted Roche GS-Junior 454 resequencing of a 156-kb region of IGF1 in 80 African American aggressive prostate cancer cases. Three hundred and thirty-four IGF1 SNPs were examined for their association with prostate cancer risk in 1,000 African American prostate cancer cases and 991 controls. The top associated SNP in African Americans, rs148371593, was examined in an additional 3,465 prostate cancer cases and 3,425 controls of non-African American ancestry-European Americans, Japanese Americans, Latinos, and Native Hawaiians. The overall association of 334 IGF1 SNPs and prostate cancer risk was assessed using logistic kernel-machine methods. The association between each SNP and prostate cancer risk was evaluated through unconditional logistic regression. A false discovery rate threshold of q < 0.1 was used to determine statistical significance of associations. We identified 8 novel IGF1 SNPs. The cumulative effect of the 334 IGF1 SNPs was not associated with prostate cancer risk (P = 0.13) in African Americans. Twenty SNPs were nominally associated with prostate cancer at P < 0.05. The top associated SNP among African Americans, rs148371593 [minor allele frequency (MAF) = 0.03; P = 0.0014; q > 0.1], did not reach our criterion of statistical significance. This polymorphism was rare in non-African Americans (MAF < 0.003) and was not associated with prostate cancer risk (P = 0.98). Our findings do not support the role of IGF1 variants and prostate cancer risk among African Americans.

  4. Testosterone and prostate cancer: an evidence-based review of pathogenesis and oncologic risk

    PubMed Central

    Michaud, Jason E.; Billups, Kevin L.; Partin, Alan W.

    2015-01-01

    Testosterone plays a central role in male development and health. Likewise, androgen deficiency, or hypogonadism, is associated with a variety of symptoms including decreased energy, diminished libido and erectile dysfunction, among others. Male androgen levels steadily decline with age, and, in a subset of symptomatic older men, can result in late-onset hypogonadism (LOH). Over the last decade, increased awareness of hypogonadism among patients and providers has led to a significant rise in the use of testosterone replacement therapy (TRT) for hypogonadism, and especially in LOH. Accompanying the rise in TRT are concerns of potential adverse effects, including cardiovascular risks and the promotion of prostate cancer. The ‘androgen hypothesis’ asserts that prostate cancer development and progression is driven by androgens, and thus TRT has the theoretical potential to drive prostate cancer development and progression. In this review, we examine existing data surrounding testosterone and prostate cancer. There is significant evidence that androgens promote prostate cancer in experimental systems. However, there is no clear evidence that elevations in endogenous testosterone levels promote the development of prostate cancer in humans. As a result of experimental and historical data on the progression of prostate cancer following TRT, there has been widespread belief that TRT will promote disease progression in prostate cancer patients. Despite these fears, there are a growing number of studies demonstrating no increase in prostate cancer incidence among men on TRT. Furthermore, in studies involving a small number of patients, there has been no discernable increase in disease progression in prostate cancer patients on TRT. While data from large, prospective, randomized, controlled trials are absent, TRT in select prostate cancer patients is likely safe. In the end, the use of TRT in prostate cancer patients is still considered experimental and should only be

  5. Risks of Prostate Cancer Screening

    MedlinePlus

    ... Laboratory for Cancer Research Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer ... Centers Frederick National Lab Partners & Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer ...

  6. Imaging Localized Prostate Cancer: Current Approaches and New Developments

    PubMed Central

    Turkbey, Baris; Albert, Paul S.; Kurdziel, Karen; Choyke, Peter L.

    2012-01-01

    OBJECTIVE Prostate cancer is the most common noncutaneous malignancy among men in the Western world. Imaging has recently become more important in the diagnosis, local staging, and treatment follow-up of prostate cancer. In this article, we review conventional and functional imaging methods as well as targeted imaging approaches with novel tracers used in the diagnosis and staging of prostate cancer. CONCLUSION Although prostate cancer is the second leading cause of cancer death in men, imaging of localized prostate cancer remains limited. Recent developments in imaging technologies, particularly MRI and PET, may lead to significant improvements in lesion detection and staging. PMID:19457807

  7. Penile Rehabilitation Strategies Among Prostate Cancer Survivors.

    PubMed

    Aoun, Fouad; Peltier, Alexandre; van Velthoven, Roland

    2015-01-01

    Despite advances in technical and surgical approaches, erectile dysfunction (ED) remains the most common complication among prostate cancer survivors, adversely impacting quality of life. This article analyzes the concept and rationale of ED rehabilitation programs in prostate cancer patients. Emphasis is placed on the pathophysiology of ED after diagnosis and treatment of prostate cancer to understand the efficacy of rehabilitation programs in clinical practice. Available evidence shows that ED is a transient complication following prostate biopsy and cancer diagnosis, with no evidence to support rehabilitation programs in these patients. A small increase in ED and in the use of phosphodiesterase type 5 (PDE5) inhibitors was reported in patients under active surveillance. Patients should be advised that active surveillance is unlikely to severely affect erectile function, but clinically significant changes in sexual function are possible. Focal therapy could be an intermediate option for patients demanding treatment/refusing active surveillance and invested in maintaining sexual activity. Unlike radical prostatectomy, there is no support for PDE5 inhibitor use to prevent ED after highly conformal external radiotherapy or low-dose rate brachytherapy. Despite progress in the understanding of the pathophysiologic mechanisms responsible for ED in prostate cancer patients, the success rates of rehabilitation programs remain low in clinical practice. Alternative strategies to prevent ED appear warranted, with attention toward neuromodulation, nerve grafting, nerve preservation, stem cell therapy, investigation of neuroprotective interventions, and further refinements of radiotherapy dosing and delivery methods. PMID:27222641

  8. Penile Rehabilitation Strategies Among Prostate Cancer Survivors

    PubMed Central

    Aoun, Fouad; Peltier, Alexandre; van Velthoven, Roland

    2015-01-01

    Despite advances in technical and surgical approaches, erectile dysfunction (ED) remains the most common complication among prostate cancer survivors, adversely impacting quality of life. This article analyzes the concept and rationale of ED rehabilitation programs in prostate cancer patients. Emphasis is placed on the pathophysiology of ED after diagnosis and treatment of prostate cancer to understand the efficacy of rehabilitation programs in clinical practice. Available evidence shows that ED is a transient complication following prostate biopsy and cancer diagnosis, with no evidence to support rehabilitation programs in these patients. A small increase in ED and in the use of phosphodiesterase type 5 (PDE5) inhibitors was reported in patients under active surveillance. Patients should be advised that active surveillance is unlikely to severely affect erectile function, but clinically significant changes in sexual function are possible. Focal therapy could be an intermediate option for patients demanding treatment/refusing active surveillance and invested in maintaining sexual activity. Unlike radical prostatectomy, there is no support for PDE5 inhibitor use to prevent ED after highly conformal external radiotherapy or low-dose rate brachytherapy. Despite progress in the understanding of the pathophysiologic mechanisms responsible for ED in prostate cancer patients, the success rates of rehabilitation programs remain low in clinical practice. Alternative strategies to prevent ED appear warranted, with attention toward neuromodulation, nerve grafting, nerve preservation, stem cell therapy, investigation of neuroprotective interventions, and further refinements of radiotherapy dosing and delivery methods. PMID:27222641

  9. Fibre intake and prostate cancer risk.

    PubMed

    Pelucchi, Claudio; Talamini, Renato; Galeone, Carlotta; Negri, Eva; Franceschi, Silvia; Dal Maso, Luigino; Montella, Maurizio; Conti, Ettore; La Vecchia, Carlo

    2004-03-20

    Dietary fibre has been reported to protect from several neoplasms, but the issue remains controversial. No previous study considered in depth the topic of fibres and prostate cancer. A multicentre case-control study was conducted in Italy from 1991 to 2002, including 1,294 men with incident, histologically confirmed prostate cancer and 1,451 controls admitted to the same network of hospitals as cases with acute nonmalignant conditions. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were obtained after allowance for major identified confounding factors, including total energy intake. Compared to the lowest quintile, the OR of prostate cancer for the highest quintile of total fibre intake was 0.93 (95% CI 0.71-1.22). The risk was inversely related with soluble fibre (OR = 0.89, 95% CI 0.78-1.02, for a difference between 80th and 20th percentile), cellulose (OR = 0.88, 95% CI 0.78-1.01) and vegetable fibre (OR = 0.82, 95% CI 0.73-0.93). These relationships were consistent across strata of age, family history of prostate cancer, body mass index and education. Vegetable fibres appear, therefore, to have a favourable association with prostate cancer risk. PMID:14750181

  10. EFFECT OF DUAL INHIBITION OF APOPTOSIS AND AUTOPHAGY IN PROSTATE CANCER

    PubMed Central

    Saleem, Ahamed; Dvorzhinski, Dmitri; Santanam, Urmila; Mathew, Robin; Bray, Kevin; Stein, Mark; White, Eileen; DiPaola, Robert S.

    2013-01-01

    Purpose Targeting multiple anti-apoptotic proteins is now possible with the small molecule BH3 domain mimetics such as ABT-737. Given recent studies demonstrating that autophagy is a resistance mechanism to multiple therapeutic agents in the setting of apoptotic inhibition, we hypothesized that hydroxychloroquine (HCQ), an anti-malarial drug that inhibits autophagy, will increase cytotoxicity of ABT-737. Experimental Design Cytotoxicity of ABT-737 and HCQ was assessed in vitro in PC-3 and LNCaP cells, and in vivo in a xenograft mouse model. The role of autophagy as a resistance mechanism was assessed by siRNA knockdown of the essential autophagy gene beclin1. ROS was measured by flow cytometry, and mitophagy assessed by the mCherry-Parkin reporter. Results Induction of autophagy by ABT-737 was a mechanism of resistance in prostate cancer cell lines. Therapeutic inhibition of autophagy with HCQ increased cytotoxicity of ABT-737 both in vitro and in vivo. ABT-737 induced LC-3 and decreased p62 expression by immunoblot in cell lines and by immunohistochemistry in tumors in vivo. Assessment of ROS and mitochondria demonstrated that ROS production by ABT-737 and HCQ was a mechanism of cytotoxicity. Conclusions We demonstrated that autophagy inhibition with HCQ enhances ABT-737 cytotoxicity in vitro and in vivo, that LC-3 and p62 represent assessable markers in human tissue for future clinical trials, and that ROS induction is a mechanism of cytotoxicity. These results support a new paradigm of dual targeting of apoptosis and autophagy in future clinical studies. PMID:22241682

  11. The REDUCE trial: chemoprevention in prostate cancer using a dual 5alpha-reductase inhibitor, dutasteride.

    PubMed

    Musquera, Mireia; Fleshner, Neil E; Finelli, Antonio; Zlotta, Alexandre R

    2008-07-01

    Dutasteride, a dual 5alpha-reductase inhibitor, is used in the treatment of benign prostatic hyperplasia (BPH). It reduces serum prostate-specific antigen levels by approximately 50% at 6 months and total prostate volume by 25% after 2 years. Randomized placebo-controlled trials in BPH patients have shown the efficacy of dutasteride in symptomatic relief, improvements in quality of life and peak urinary flow rate. Side effects occurring with dutasteride are decreased libido, erectile dysfunction, ejaculation disorders and gynecomastia. Preliminary data from placebo-controlled BPH trials have shown a decrease in the detection of prostate cancer in patients treated with dutasteride, although these studies were not designed to look at this issue. Dutasteride differs from finasteride in that it inhibits both isoenzymes of 5alpha-reductase, type I and type II. The landmark Prostate Cancer Prevention Trial at the end of the 7-year study demonstrated a 24.8% reduction in the incidence of prostate cancer in the finasteride group compared with placebo. However, a 25.5% increase in the prevalence of high-grade Gleason tumors has been observed, the clinical significance of which has been debated. Preliminary data suggest a decrease in prostate cancer incidence in dutasteride-treated patients and demonstrate type I alphareductase enzyme expression in prostate cancer. As a result, dutasteride is being investigated for prostate cancer prevention in the ongoing Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, which is discussed here. PMID:18588452

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

    PubMed Central

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

    2016-01-01

    Introduction Cancer center websites are trusted sources of internet information about treatment options for prostate cancer. The quality of information on these websites is unknown. The objective of this study was to evaluate the quality of information on cancer center websites addressing prostate cancer treatment options, outcomes, and toxicity. Materials and methods We evaluated the websites of all National Cancer Institute-designated cancer centers to determine if sufficient information was provided to address eleven decision-specific knowledge questions from the validated Early Prostate Cancer Treatment Decision Quality Instrument. We recorded the number of questions addressed, the number of clicks to reach the prostate cancer-specific webpage, evaluation time, and Spanish and mobile accessibility. Correlation between evaluation time and questions addressed were calculated using the Pearson coefficient. Results Sixty-three websites were reviewed. Eighty percent had a prostate cancer-specific webpage reached in a median of three clicks. The average evaluation time was 6.5 minutes. Information was available in Spanish on 24% of sites and 59% were mobile friendly. Websites provided sufficient information to address, on average, 19% of questions. No website addressed all questions. Evaluation time correlated with the number of questions addressed (R2 = 0.42, p < 0.001). Conclusions Cancer center websites provide insufficient information for men with localized prostate cancer due to a lack of information about and direct comparison of specific treatment outcomes and toxicities. Information is also less accessible in Spanish and on mobile devices. These data can be used to improve the quality and accessibility of prostate cancer treatment information on cancer center websites. PMID:27226941

  13. Hydrogen Sulfide Signaling Axis as a Target for Prostate Cancer Therapeutics

    PubMed Central

    Liu, Mingzhe; Wu, Lingyun; Montaut, Sabine; Yang, Guangdong

    2016-01-01

    Hydrogen sulfide (H2S) was originally considered toxic at elevated levels; however just in the past decade H2S has been proposed to be an important gasotransmitter with various physiological and pathophysiological roles in the body. H2S can be generated endogenously from L-cysteine by multiple enzymes, including cystathionine gamma-lyase, cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase in combination with cysteine aminotransferase. Prostate cancer is a major health concern and no effective treatment for prostate cancers is available. H2S has been shown to inhibit cell survival of androgen-independent, androgen-dependent, and antiandrogen-resistant prostate cancer cells through different mechanisms. Various H2S-releasing compounds, including sulfide salts, diallyl disulfide, diallyl trisulfide, sulforaphane, and other polysulfides, also have been shown to inhibit prostate cancer growth and metastasis. The expression of H2S-producing enzyme was reduced in both human prostate cancer tissues and prostate cancer cells. Androgen receptor (AR) signaling is indispensable for the development of castration resistant prostate cancer, and H2S was shown to inhibit AR transactivation and contributes to antiandrogen-resistant status. In this review, we summarized the current knowledge of H2S signaling in prostate cancer and described the molecular alterations, which may bring this gasotransmitter into the clinic in the near future for developing novel pharmacological and therapeutic interventions for prostate cancer. PMID:27019751

  14. Multimodality Therapy: Bone-Targeted Radioisotope Therapy of Prostate Cancer

    PubMed Central

    Tu, Shi-Ming; Lin, Sue-Hwa; Podoloff, Donald A.; Logothetis, Christopher J.

    2016-01-01

    Accumulating data suggest that bone-seeking radiopharmaceuticals can be used to treat prostate cancer bone metastasis and improve the clinical outcome of patients with advanced prostate cancer. It remains to be elucidated whether radiopharmaceuticals enhance the disruption of the onco-niche or the eradication of micrometastatic cells in the bone marrow. The purpose of this review is to investigate the role of bone-targeted radioisotope therapy in the setting of multimodality therapy for advanced prostate cancer. We examine available data and evaluate whether dose escalation, newer generations, or repeated dosing of radiopharmaceuticals enhance their antitumor effects and whether their combination with hormone ablative therapy, chemotherapy, or novel targeted therapy can improve clinical efficacy. PMID:20551894

  15. Unravelling ``off-target'' effects of redox-active polymers and polymer multilayered capsules in prostate cancer cells

    NASA Astrophysics Data System (ADS)

    Beretta, Giovanni L.; Folini, Marco; Cavalieri, Francesca; Yan, Yan; Fresch, Enrico; Kaliappan, Subramanian; Hasenöhrl, Christoph; Richardson, Joseph J.; Tinelli, Stella; Fery, Andreas; Caruso, Frank; Zaffaroni, Nadia

    2015-03-01

    Redox-active polymers and carriers are oxidizing nanoagents that can potentially trigger intracellular off-target effects. In the present study, we investigated the occurrence of off-target effects in prostate cancer cells following exposure to redox-active polymer and thin multilayer capsules with different chemical properties. We show that, depending on the intracellular antioxidant capacity, thiol-functionalized poly(methacrylic acid), PMASH triggers cell defense responses/perturbations that result in off-target effects (i.e., induction of autophagy and down-regulation of survivin). Importantly, the conversion of the carboxyl groups of PMASH into the neutral amides of poly(hydroxypropylmetacrylamide) (pHPMASH) nullified the off-target effects and cytotoxicity in tested cell lines. This suggests that the simultaneous action of carboxyl and disulfide groups in PMASH polymer or capsules may play a role in mediating the intracellular off-target effects. Our work provides evidence that the rational design of redox-active carriers for therapeutic-related application should be guided by a careful investigation on potential disturbance of the cellular machineries related to the carrier association.Redox-active polymers and carriers are oxidizing nanoagents that can potentially trigger intracellular off-target effects. In the present study, we investigated the occurrence of off-target effects in prostate cancer cells following exposure to redox-active polymer and thin multilayer capsules with different chemical properties. We show that, depending on the intracellular antioxidant capacity, thiol-functionalized poly(methacrylic acid), PMASH triggers cell defense responses/perturbations that result in off-target effects (i.e., induction of autophagy and down-regulation of survivin). Importantly, the conversion of the carboxyl groups of PMASH into the neutral amides of poly(hydroxypropylmetacrylamide) (pHPMASH) nullified the off-target effects and cytotoxicity in tested cell

  16. New strategies against prostate cancer--Pt(II)-based chemotherapy.

    PubMed

    Matos, C S; de Carvalho, A L M B; Lopes, R P; Marques, M P M

    2012-01-01

    Prostate cancer is the second most common cancer worldwide and the sixth cause of cancer-related death in men. When hormone therapy fails to control tumour growth, castration-resistant prostate cancer (CRPC) occurs and chemotherapy drugs must be administered. Since 2004, docetaxel administration is the standard of care in metastatic CRPC, although it presents severe limitations such as acquired resistance and poor prognosis. An analogue (cabazitaxel) was approved by the FDA in 2010 as a second-line chemotherapeutic agent. Novel immuno- and hormonal therapy agents, as well as tumour vaccines, have been recently developed, but new strategies are still needed for effectively handling this type of neoplasia. Platinum compounds, in particular, have been the object of a growing interest, despite the former belief that they should have modest activity against prostate cancer. Compounds such as carboplatin, oxaliplatin or satraplatin, either alone or in combination, have lately shown promising results. In order to overcome the deleterious side-effects usually associated to these metal-based agents, several approaches have been followed with a view to optimise drug delivery and targeting, some of which showed considerable success in CRPC. Platinum drugs may therefore have an important role in the chemotherapeutic management of human metastatic castration-resistant prostate cancer, mostly in second-line strategies. The present review addresses the most relevant studies on platinum-based antineoplastic agents towards CRPC in the last decade--from first--and second-generation complexes to newly developed compounds.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  19. Symptom Management Strategies for Men with Early-Stage Prostate Cancer: Results from the Prostate Cancer Patient Education Program (PCPEP)

    PubMed Central

    Vij, Alok; Kowalkowski, Marc A.; Hart, Tae; Goltz, Heather Honoré; Hoffman, David J.; Knight, Sara J.; Caroll, Peter R.

    2013-01-01

    While the literature on prostate cancer health-related quality of life has grown extensively, little is known about symptom management strategies used by men to manage treatment-related side effects and the effectiveness of those strategies. We collected 628 symptom management reports from 98 men treated for localized prostate cancer. Participants were recruited from email lists and a prostate cancer clinic in Northern California. Data were collected using the Critical Incident Technique. Symptom management reports were assigned to categories of urinary, sexual, bowel, mental health, systemic, or “other.” We calculated descriptive statistics by symptom type and management strategy effectiveness. The most common symptoms were urinary (26 %) and sexual (23 %). Participants’ symptom management strategies varied widely, from medical and surgical interventions (20 %) to behavioral strategies (11 %) to diet and lifestyle interventions (12 %). The effectiveness of symptom management strategies varied, with sexual symptoms being managed effectively only 47 % of the time to mental health symptom management strategies considered effective 89 % of the time. Doing nothing was a commonly reported (15 %) response to symptoms and was effective only 14 % of the time. Men report the least effectiveness in symptom management for sexual dysfunction after prostate cancer treatment. Including men’s experience with managing treatment side effects may be an important way to improve survivorship programs and make them more acceptable to men. More work is needed to find out why men frequently do nothing in response to symptoms when effective solutions exist and how providers can successfully engage such men. PMID:23996206

  20. Novel bourgeonal fragrance conjugates for the detection of prostate cancer.

    PubMed

    Sturzu, Alexander; Sheikh, Sumbla; Echner, Hartmut; Nägele, Thomas; Deeg, Martin; Schwentner, Christian; Horger, Marius; Ernemann, Ulrike; Heckl, Stefan

    2013-10-01

    The methods used for detection of prostate cancer and prostate cancer lymph node metastases in medical diagnostics leave room for improvement. Currently, no means of identifying metastasized lymph nodes other than biopsies is available. Markers which are exclusively found on prostate cancer cells present a focal point for potential imaging methods. To complement the established markers like e.g. PCA3-a noncoding mRNA sequence-and PSA-a serine protease-we investigated the ectopically expressed G-protein coupled olfactory receptor OR1D2 as a possible target for prostate-specific detection with its agonist bourgeonal which has been conjugated to two different fluorescent dyes. We performed mRNA expression analysis of the OR1D2 receptor mRNA by reverse transcriptase polymerase chain reaction on LNCaP prostate carcinoma cells and three other non-prostate derived carcinoma cell lines. Additionally, we used flow cytometry to investigate the uptake of fluorescent-dye-bound OR1D2-ligand bourgeonal into the examined carcinoma cell lines. Finally, confocal laser scanning microscopy of in vitro cell culture and in vivo tumor xenografts on mice was performed. We could confirm OR1D2 receptor mRNA overexpression as well as stronger uptake of both bourgeonal conjugates in vitro and in vivo for LNCaP cells compared to the non-prostate derived cell lines. Cytoplasmic accumulation and no adverse effects after in vitro and in vivo application of the conjugates were observed. The conjugates represent a platform for the development of future prostate-specific imaging applications, e.g. detection of metastasized lymph nodes during surgery by intraoperative laser examination.

  1. In vitro anti-oxidant, cytotoxic and pro-apoptotic effects of Achillea teretifolia Willd extracts on human prostate cancer cell lines

    PubMed Central

    Bali, Elif Burcu; Açık, Leyla; Elçi, Pınar; Sarper, Meral; Avcu, Ferit; Vural, Mecit

    2015-01-01

    Background: The majority of Achillea species are the most important native economic plants of Anatolia. They include highly bioactive compounds, so they have therapeutic applications. Objective: In the present study, the aim was to investigate in vitro anti-oxidant, cytotoxic and pro-apoptotic effects of Achillea teretifolia Willd extracts (Turkish name: Beyaz civanperÇemi). Materials and Methods: The anti-oxidant potential of the extracts was analyzed by the free radical 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and total phenolic content methods. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to detect cytotoxicity of the extracts onhuman prostate cancer cell lines (DU145 and PC-3) and human gingival fibroblast (HGF) cells. mRNA expression levels of pro-apoptotic (bax, caspase-3) and anti-apoptotic (bcl-2) genes were measured by quantitative real-time polymerase chain reaction. Results: The results showed that extracts exhibited a remarkable DPPH scavenging activity, and total phenolic content of the methanol extract was higher than that of the water extract. As time and concentration were increased, the methanol extract exhibited a more powerful cytotoxic effect on prostate cancer cells. In prostate cancer cells, the levels of mRNA expression of the bax and caspase-3 genes were significantly up-regulated (P < 0.05), whereas the expression of bcl-2 was down-regulated (P < 0.05). In HGF cells, there were no cytotoxic effect and apoptosis induction triggered by the extracts. Conclusion: The methanol extract had more powerful anti-oxidant, cytotoxic and pro-apoptotic effects than the water extract. The extracts could be good anti-oxidant sources, and they might include anti-cancer compounds triggering the cytotoxicity and the apoptosis on prostate cancer cells. PMID:26664020</