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Sample records for finnish prostate cancer

  1. 5-Alpha reductase inhibitor use and prostate cancer survival in the Finnish Prostate Cancer Screening Trial.

    PubMed

    Murtola, Teemu J; Karppa, Elina K; Taari, Kimmo; Talala, Kirsi; Tammela, Teuvo Lj; Auvinen, Anssi

    2016-06-15

    Randomized clinical trials have shown that use of 5α-reductase inhibitors (5-ARIs) lowers overall prostate cancer (PCa) risk compared to placebo, while the proportion of Gleason 8-10 tumors is elevated. It is unknown whether this affects PCa-specific survival. We studied disease-specific survival by 5-ARI usage in a cohort of 6,537 prostate cancer cases diagnosed in the Finnish Prostate Cancer Screening Trial and linked to the national prescription database for information on medication use. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals for prostate cancer-specific deaths. For comparison, survival among alpha-blocker users was also evaluated. During the median follow-up of 7.5 years after diagnosis a total of 2,478 men died; 617 due to prostate cancer and 1,861 due to other causes. The risk of prostate cancer death did not differ between 5-ARI users and nonusers (multivariable adjusted HR 0.94, 95% CI 0.72-1.24 and HR 0.98, 95% CI 0.69-1.41 for usage before and after the diagnosis, respectively). Alpha-blocker usage both before and after diagnosis was associated with increased risk of prostate cancer death (HR 1.29, 95% CI 1.08-1.54 and HR 1.56, 95% CI 1.30-1.86, respectively). The risk increase vanished in long-term alpha-blocker usage. Use of 5-ARIs does not appear to affect prostate cancer mortality when used in management of benign prostatic hyperplasia. Increased risk associated with alpha-blocker usage should prompt further exploration on the prognostic role of lower urinary tract symptoms. PMID:26804670

  2. Non-Steroidal Anti-Inflammatory Drugs and Cancer Death in the Finnish Prostate Cancer Screening Trial

    PubMed Central

    Veitonmäki, Thea; Murtola, Teemu J.; Talala, Kirsi; Taari, Kimmo; Tammela, Teuvo; Auvinen, Anssi

    2016-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, have been associated with lowered cancer incidence and mortality. We examined overall cancer mortality and mortality from specific cancer sites among the 80,144 men in the Finnish Prostate Cancer Screening Trial. Information on prescription drug use was acquired from the national drug reimbursement database. Over-the-counter use information was gathered by a questionnaire. Hazard ratios (HR) and 95% confidence intervals (CI) by prescription and over-the-counter NSAID use for overall and specific cancer deaths were calculated using Cox regression. During the median follow-up time of 15 years, 7,008 men died from cancer. Men with prescription NSAID use had elevated cancer mortality (HR 2.02 95% CI 1.91–2.15) compared to non-users. The mortality risk was increased for lung, colorectal and pancreas cancer mortality (HR 2.68, 95%CI 2.40–2.99, HR 1.91, 95% CI 1.57–2.32 and HR 1.93, 95% CI 1.58–2.37, respectively). The increased risk remained in competing risks regression (HR 1.11, 95% CI 1.05–1.18). When the usage during the last three years of follow-up was excluded, the effect was reversed (HR 0.69, 95% CI 0.65–0.73). Cancer mortality was not decreased for prescription or over-the-counter aspirin use. However, in the competing risk regression analysis combined prescription and over-the-counter aspirin use was associated with decreased overall cancer mortality (HR 0.76, 95% CI 0.70–0.82). Cancer mortality was increased for NSAID users. However, the risk disappeared when the last 3 years were excluded. PMID:27100876

  3. Non-Steroidal Anti-Inflammatory Drugs and Cancer Death in the Finnish Prostate Cancer Screening Trial.

    PubMed

    Veitonmäki, Thea; Murtola, Teemu J; Talala, Kirsi; Taari, Kimmo; Tammela, Teuvo; Auvinen, Anssi

    2016-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, have been associated with lowered cancer incidence and mortality. We examined overall cancer mortality and mortality from specific cancer sites among the 80,144 men in the Finnish Prostate Cancer Screening Trial. Information on prescription drug use was acquired from the national drug reimbursement database. Over-the-counter use information was gathered by a questionnaire. Hazard ratios (HR) and 95% confidence intervals (CI) by prescription and over-the-counter NSAID use for overall and specific cancer deaths were calculated using Cox regression. During the median follow-up time of 15 years, 7,008 men died from cancer. Men with prescription NSAID use had elevated cancer mortality (HR 2.02 95% CI 1.91-2.15) compared to non-users. The mortality risk was increased for lung, colorectal and pancreas cancer mortality (HR 2.68, 95%CI 2.40-2.99, HR 1.91, 95% CI 1.57-2.32 and HR 1.93, 95% CI 1.58-2.37, respectively). The increased risk remained in competing risks regression (HR 1.11, 95% CI 1.05-1.18). When the usage during the last three years of follow-up was excluded, the effect was reversed (HR 0.69, 95% CI 0.65-0.73). Cancer mortality was not decreased for prescription or over-the-counter aspirin use. However, in the competing risk regression analysis combined prescription and over-the-counter aspirin use was associated with decreased overall cancer mortality (HR 0.76, 95% CI 0.70-0.82). Cancer mortality was increased for NSAID users. However, the risk disappeared when the last 3 years were excluded. PMID:27100876

  4. 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 ...

  5. Serum phytanic and pristanic acid levels and prostate cancer risk in Finnish smokers.

    PubMed

    Wright, Margaret E; Albanes, Demetrius; Moser, Ann B; Weinstein, Stephanie J; Snyder, Kirk; Männistö, Satu; Gann, Peter H

    2014-12-01

    Phytanic acid is a saturated branched-chain fatty acid found predominantly in red meat and dairy products, and may contribute to the elevated risks of prostate cancer associated with higher consumption of these foods. Pristanic acid is formed during peroxisomal oxidation of phytanic acid, and is the direct substrate of α-Methyl-CoA-Racemase (AMACR)--an enzyme that is consistently overexpressed in prostate tumors relative to benign tissue. We measured phytanic and pristanic acids as percentages of total fatty acids by gas chromatography-mass spectrometry in prediagnostic blood samples from 300 prostate cancer cases and 300 matched controls, all of whom were participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study supplementation trial and follow-up cohort. In addition to providing a fasting blood sample at baseline, all men completed extensive diet, lifestyle, and medical history questionnaires. Among controls, the strongest dietary correlates of serum phytanic and pristanic acids were saturated fat, dairy fat, and butter (r = 0.50 and 0.40, 0.46 and 0.38, and 0.40 and 0.37, respectively; all P-values <0.001). There was no association between serum phytanic acid and risk of total or aggressive prostate cancer in multivariate logistic regression models (for increasing quartiles, odds ratios (OR) and 95% confidence intervals (CI) for aggressive cancer were 1.0 (referent), 1.62 (0.97-2.68), 1.12 (0.66-1.90), and 1.14 (0.67-1.94), P(trend) = 0.87). Pristanic acid was strongly correlated with phytanic acid levels (r = 0.73, P < 0.0001), and was similarly unrelated to prostate cancer risk. Significant interactions between phytanic and pristanic acids and baseline circulating β-carotene concentrations were noted in relation to total and aggressive disease among participants who did not receive β-carotene supplements as part of the original ATBC intervention trial. In summary, we observed no overall association between serum phytanic and

  6. Serum phytanic and pristanic acid levels and prostate cancer risk in Finnish smokers

    PubMed Central

    Wright, Margaret E; Albanes, Demetrius; Moser, Ann B; Weinstein, Stephanie J; Snyder, Kirk; Männistö, Satu; Gann, Peter H

    2014-01-01

    Phytanic acid is a saturated branched-chain fatty acid found predominantly in red meat and dairy products, and may contribute to the elevated risks of prostate cancer associated with higher consumption of these foods. Pristanic acid is formed during peroxisomal oxidation of phytanic acid, and is the direct substrate of α-Methyl-CoA-Racemase (AMACR)—an enzyme that is consistently overexpressed in prostate tumors relative to benign tissue. We measured phytanic and pristanic acids as percentages of total fatty acids by gas chromatography-mass spectrometry in prediagnostic blood samples from 300 prostate cancer cases and 300 matched controls, all of whom were participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study supplementation trial and follow-up cohort. In addition to providing a fasting blood sample at baseline, all men completed extensive diet, lifestyle, and medical history questionnaires. Among controls, the strongest dietary correlates of serum phytanic and pristanic acids were saturated fat, dairy fat, and butter (r = 0.50 and 0.40, 0.46 and 0.38, and 0.40 and 0.37, respectively; all P-values <0.001). There was no association between serum phytanic acid and risk of total or aggressive prostate cancer in multivariate logistic regression models (for increasing quartiles, odds ratios (OR) and 95% confidence intervals (CI) for aggressive cancer were 1.0 (referent), 1.62 (0.97–2.68), 1.12 (0.66–1.90), and 1.14 (0.67–1.94), Ptrend = 0.87). Pristanic acid was strongly correlated with phytanic acid levels (r = 0.73, P < 0.0001), and was similarly unrelated to prostate cancer risk. Significant interactions between phytanic and pristanic acids and baseline circulating β-carotene concentrations were noted in relation to total and aggressive disease among participants who did not receive β-carotene supplements as part of the original ATBC intervention trial. In summary, we observed no overall association between serum phytanic and

  7. Prostate cancer

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000380.htm Prostate cancer To use the sharing features on this page, please enable JavaScript. Prostate cancer is cancer that starts in the prostate gland. ...

  8. Finnish Fanconi anemia mutations and hereditary predisposition to breast and prostate cancer.

    PubMed

    Mantere, T; Haanpää, M; Hanenberg, H; Schleutker, J; Kallioniemi, A; Kähkönen, M; Parto, K; Avela, K; Aittomäki, K; von Koskull, H; Hartikainen, J M; Kosma, V-M; Laasanen, S-L; Mannermaa, A; Pylkäs, K; Winqvist, R

    2015-07-01

    Mutations in downstream Fanconi anemia (FA) pathway genes, BRCA2, PALB2, BRIP1 and RAD51C, explain part of the hereditary breast cancer susceptibility, but the contribution of other FA genes has remained questionable. Due to FA's rarity, the finding of recurrent deleterious FA mutations among breast cancer families is challenging. The use of founder populations, such as the Finns, could provide some advantage in this. Here, we have resolved complementation groups and causative mutations of five FA patients, representing the first mutation confirmed FA cases in Finland. These patients belonged to complementation groups FA-A (n = 3), FA-G (n = 1) and FA-I (n = 1). The prevalence of the six FA causing mutations was then studied in breast (n = 1840) and prostate (n = 565) cancer cohorts, and in matched controls (n = 1176 females, n = 469 males). All mutations were recurrent, but no significant association with cancer susceptibility was observed for any: the prevalence of FANCI c.2957_2969del and c.3041G>A mutations was even highest in healthy males (1.7%). This strengthens the exclusive role of downstream genes in cancer predisposition. From a clinical point of view, current results provide fundamental information of the mutations to be tested first in all suspected FA cases in Finland. PMID:24989076

  9. Hemochromatosis gene mutations among Finnish male breast and prostate cancer patients.

    PubMed

    Syrjäkoski, Kirsi; Fredriksson, Henna; Ikonen, Tarja; Kuukasjärvi, Tuula; Autio, Ville; Matikainen, Mika P; Tammela, Teuvo L J; Koivisto, Pasi A; Schleutker, Johanna

    2006-01-15

    Hereditary hemochromatosis (HH), the most common genetic disease in northern Europeans, is an autosomal recessive disorder of iron metabolism. The association between hepatocellular carcinoma and HFE homozygosity is well documented, but recently HFE hetero- and homozygosity has also been linked to nonhepatocellular malignancies, including female breast cancer. We hypothesized that C282Y and H63D mutations in the HFE gene could contribute to male breast cancer (MBC) and prostate cancer (PC) susceptibility at the population level in Finland. We screened the 2 major HFE mutations, H63D and C282Y, from 116 MBC cases diagnosed in Finland between 1967 and 1996, 843 consecutive unselected PC cases diagnosed at the Pirkanmaa Hospital District between 1999 and 2001 and 480 anonymous blood donor controls by minisequencing. Our results indicate that the frequencies of the HFE mutations do not significantly differ between MBC and PC patients and the population-based controls. No significantly altered risks for MBC or PC among carriers of the 2 variants were observed. However, HFE mutations were seen twice as often among carriers of a common BRCA2 mutation 9346(-2)A-->G compared with the rest of the MBC cases, indicating that HFE may be an MBC risk modifier gene among BRCA2 mutation carriers. In conclusion, our results indicate a minor role for the HFE mutations C282Y and H63D in the causation of MBC and PC, but carriers of both BRCA2 9346(-2)A-->G and an HFE mutation may be at an increased risk. PMID:16003728

  10. Prostate cancer

    SciTech Connect

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

    1987-01-01

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

  11. 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 ...

  12. Prostate Cancer

    MedlinePlus

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

  13. 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 ...

  14. 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

  15. Postscreening follow-up of the Finnish Prostate Cancer Screening Trial on putative prostate cancer risk factors: vitamin and mineral use, male pattern baldness, pubertal development and non-steroidal anti-inflammatory drug use.

    PubMed

    Sarre, Sami; Määttänen, Liisa; Tammela, Teuvo L J; Auvinen, Anssi; Murtola, Teemu J

    2016-08-01

    Objective The etiology of prostate cancer (PCa) is still unclear. This study aimed to investigate the association between PCa risk and the indicators of endogenous androgen production at puberty, male pattern baldness, over-the-counter use of non-steroidal anti-inflammatory drugs and vitamin supplement use. Materials and methods Participants in the third round of the Finnish Prostate Cancer Screening Trial were sent a survey on possible PCa risk factors and 11,795 out of 12,740 (93%) men returned the questionnaire. PCa cases were identified from the Finnish Cancer Registry. Results During the median follow-up of 6.6 years, 757 PCa cases were diagnosed and 21 men died from PCa. Compared to earlier onset, puberty onset after 15 years of age was associated with a borderline significant decrease in PCa risk [hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.75-1.00] but not with PCa mortality. Weekly use of ibuprofen was associated with an increased risk of PCa overall (HR 1.43, 95% CI 1.08-1.91) and with metastatic PCa (HR 1.49, 95% CI 1.12-1.99) compared to less frequent use. No statistically significant association was found between vitamin use and PCa. Conclusions This study suggests that the timing of initiation of endogenous androgen production at puberty may have importance for later PCa development. Current use of over-the-counter ibuprofen is associated with an increased risk of PCa. There was no evidence of any protective effects of vitamin use on PCa risk. PMID:26927237

  16. Prostate cancer.

    PubMed

    Attard, Gerhardt; Parker, Chris; Eeles, Ros A; Schröder, Fritz; Tomlins, Scott A; Tannock, Ian; Drake, Charles G; de Bono, Johann S

    2016-01-01

    Much progress has been made in research for prostate cancer in the past decade. There is now greater understanding for the genetic basis of familial prostate cancer with identification of rare but high-risk mutations (eg, BRCA2, HOXB13) and low-risk but common alleles (77 identified so far by genome-wide association studies) that could lead to targeted screening of patients at risk. This is especially important because screening for prostate cancer based on prostate-specific antigen remains controversial due to the high rate of overdiagnosis and unnecessary prostate biopsies, despite evidence that it reduces mortality. Classification of prostate cancer into distinct molecular subtypes, including mutually exclusive ETS-gene-fusion-positive and SPINK1-overexpressing, CHD1-loss cancers, could allow stratification of patients for different management strategies. Presently, men with localised disease can have very different prognoses and treatment options, ranging from observation alone through to radical surgery, with few good-quality randomised trials to inform on the best approach for an individual patient. The survival of patients with metastatic prostate cancer progressing on androgen-deprivation therapy (castration-resistant prostate cancer) has improved substantially. In addition to docetaxel, which has been used for more than a decade, in the past 4 years five new drugs have shown efficacy with improvements in overall survival leading to licensing for the treatment of metastatic castration-resistant prostate cancer. Because of this rapid change in the therapeutic landscape, no robust data exist to inform on the selection of patients for a specific treatment for castration-resistant prostate cancer or the best sequence of administration. Moreover, the high cost of the newer drugs limits their widespread use in several countries. Data from continuing clinical and translational research are urgently needed to improve, and, crucially, to personalise management. PMID

  17. Prostate cancer - resources

    MedlinePlus

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

  18. 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 ...

  19. 6 Common Cancers - Prostate Cancer

    MedlinePlus

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

  20. 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 ...

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

    PubMed Central

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

    2016-01-01

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

  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. [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

  4. 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 ...

  5. Prostate cancer screenings

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000846.htm Prostate cancer screenings To use the sharing features on this ... present it is not clear if screening for prostate cancer is helpful for most men. For this reason, ...

  6. Prostate Cancer Foundation

    MedlinePlus

    ... PCF Spotlight Prostate Cancer Foundation and Major League Baseball Step Up To The Plate To Raise Awareness ... Foundation News Prostate Cancer Foundation and Major League Baseball Step Up To The Plate To Raise Awareness ...

  7. 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 ...

  8. Prostate Cancer Research Trial Helps John Spencer Treat His Cancer

    MedlinePlus

    ... please turn Javascript on. Feature: Prostate Cancer Prostate Cancer Research Trial Helps John Spencer Treat His Cancer Past ... Prostate Cancer" Articles Progress Against Prostate Cancer / Prostate Cancer Research Trial Helps John Spencer Treat His Cancer / Prostate ...

  9. Cryotherapy for prostate cancer

    MedlinePlus

    Cryotherapy uses very cold temperatures to freeze and kill prostate cancer cells. The goal of cryosurgery is ... Possible short-term side effects of cryotherapy for prostate ... of the penis or scrotum Problems controlling your bladder (more ...

  10. 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.

  11. 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 ...

  12. Hormone therapy for prostate cancer

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000908.htm Hormone therapy for prostate cancer To use the sharing ... helps slow the growth of prostate cancer. Male Hormones and Prostate Cancer Androgens are male sex hormones. ...

  13. Prostate cancer staging

    MedlinePlus

    ... effects of treatment The chance that treatment can cure your cancer or help you in other ways With stage ... III prostate cancer, the main goal is to cure the cancer by treating it and keeping it from coming ...

  14. 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 ...

  15. Prostate cancer screenings

    MedlinePlus

    Prostate-specific antigen (PSA) test is a blood test that checks the level of PSA in your blood. In some cases, a high level of PSA could mean you have prostate cancer. But other conditions can also cause a high level, such as infection in the prostate or ...

  16. 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 ...

  17. Prostate cancer - treatment

    MedlinePlus

    ... when cancer has spread to the bone. External beam radiation therapy uses high-powered x-rays pointed ... radiation therapy used to treat prostate cancer. Proton beams target the tumor precisely, so there is less ...

  18. 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 ...

  19. 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 ...

  20. 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.

  1. 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

  2. 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 ...

  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. 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 ...

  5. Cancer incidence among Finnish nuclear reactor workers.

    PubMed

    Auvinen, Anssi; Pukkala, Eero; Hyvönen, Hannu; Hakama, Matti; Rytömaa, Tapio

    2002-07-01

    Because of their well-documented exposures to repeated low doses of ionizing radiation, nuclear reactor workers offer an opportunity to assess cancer risk from low-dose radiation. A cohort of all 15,619 Finnish nuclear reactor workers was established through dose-monitoring records. A questionnaire survey revealed no substantial differences in consumption of tobacco or alcohol between different exposure groups nor between nuclear power company employees and contract workers. In the follow-up for cancer incidence, no clear excess in cancer incidence was observed overall, nor was any observed in any of the specific cancer types studied. There was little evidence for an association between cancer incidence and cumulative radiation dose, but the statistical power was limited. More precise estimates will be available from an international collaborative study of nuclear industry workers, including our cohort. PMID:12134527

  6. Screening for prostate cancer.

    PubMed Central

    Cher, M L; Carroll, P R

    1995-01-01

    Prostate cancer is a serious health care problem in the United States. Whether or not to screen for it has become a timely issue. Although a large number of men have clinically important, asymptomatic, undetected prostate cancer, an even larger number have clinically unimportant cancer. To justify screening programs, not only must we avoid detecting biologically unimportant cancers, we must also detect and effectively treat that subset of tumors that, if undiagnosed, would progress, produce symptoms, and reduce life expectancy. Serum prostate-specific antigen (PSA) assay, or its variations such as PSA density, PSA velocity, and age-specific reference ranges, and the digital rectal examination are the best tests for detecting clinically important, asymptomatic, curable tumors. Recent data suggest that using serum PSA levels does not result in an overdetection of unimportant tumors. Highly effective, curative treatment of localized prostate cancer is available. These factors promote optimism that screening for prostate cancer will ultimately prove beneficial. Nonetheless, men should be informed regarding the benefits and possible risks before being screened for prostate cancer. PMID:7536993

  7. 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

  8. Changing cancer risk pattern among Finnish hairdressers.

    PubMed

    Pukkala, E; Nokso-Koivisto, P; Roponen, P

    1992-01-01

    A cohort of 3637 female and 168 male hair-dressers in Finland was followed up for cancer through the Finnish Cancer Registry in 1970-1987. Compared with the total population, the women had a significantly elevated risk (standardized incidence ratio 1.7) during the first third of the observation period, but not thereafter. For the total follow-up period, the relative risks were highest for nonmelanoma skin cancer (2.0), lung cancer (1.7), ovarian cancer (1.6), cervical cancer (1.5), and cancer of the pancreas (1.5); only the risk of ovarian cancer was statistically significant. A decrease in relative risk with time was observed for many primary sites, e.g., pancreas, cervix uteri, central nervous system, and thyroid. The opposite was true for lung and skin: An increased risk was found only in 1982-1987. The excess was most prominent in the oldest age groups with the longest time span since the first employment as a hairdresser. Among men, too, the general cancer risk was highest (1.6) during the first third of the observation period. An excess of cancers of the lung and the pancreas was observed. The small numbers, however, did not allow any further conclusions. The changes in the cancer risk pattern over time may be associated with changes in working conditions in hairdressing salons. PMID:1399013

  9. Immunotherapy in prostate cancer.

    PubMed

    Sobol, Ilya; Thompson, R H; Dong, Haidong; Krco, Christopher; Kwon, Eugene D

    2015-06-01

    Immunotherapy for the treatment of malignant neoplasms has made significant progress over the last 20 years. Multiple molecular targets and clinical agents have been developed recently, particularly in the field of metastatic adenocarcinoma of the prostate. Sipuleucel-T is currently the only FDA approved immunotherapy for prostate cancer. PSA-TRICOM (Prostvac) currently has a phase III randomized trial underway after a phase II trial showed an improvement in overall survival. Interestingly, both these agents showed improvement in overall survival with no measurable change in disease state, leading to significant controversy as the utility of these agents in prostate cancer. Ipilimumab revealed a benefit for a sub-cohort of men in a post-docetaxel group and is currently undergoing investigation in a pre-docetaxel group. There are a number of other targets such as PD-1 which have shown effectiveness in other neoplasms that will likely be investigated in the future for use in prostate cancer. PMID:25894495

  10. 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 ...

  11. 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.

  12. Clinical Perspective of Prostate Cancer.

    PubMed

    Patil, Nilesh; Gaitonde, Krishnanath

    2016-06-01

    Prostate cancer is the most common noncutaneous cancer affecting men today. It largely affects men in the fifth and sixth decade of life. Screening for prostate cancer, though controversial, is still the only way to detect early prostate cancer. Multiple newer options such as blood tests and genetic markers are being used in the clinical domain today to improve cancer detection and avoid unnecessary biopsies. To date, biopsy of the prostate remains the only modality to stratify the grade of cancer. Significant improvements in the imaging technology have improved localizing and detecting the disease. Treatment of prostate cancer is stratified on the basis of the grade and volume of the disease. There are multiple treatment options involved in the management of prostate cancer. Treatment of localized prostate cancer still continues to have very high cure rates and long-term cancer-specific survival rates. PMID:27187167

  13. MYC and Prostate Cancer

    PubMed Central

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

    2010-01-01

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

  14. 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

  15. Radioimmunoscintigraphy of prostate cancer

    SciTech Connect

    Babaian, R.J.; Lamki, L.M. )

    1989-10-01

    The development of hybridoma technology has increased research efforts and clinical applications in the area of radioimmunodetection. Despite the many investigative antibodies directed against prostatic tissue or prostate cancer cell lines, only two have been tested in clinical trials. A 111In-labeled antibody directed against prostate-specific antigen, the best available serum tumor marker for prostate cancer, has shown poor sensitivity in limited clinical radioimmunoimaging trials. Monoclonal antibodies against prostatic acid phosphatase have shown better imaging results, particularly at higher antibody doses (greater than or equal to 40 mg). The limitations of this antibody include the poor results in detecting soft tissue lesions, including the primary lesion; the development of human antimouse antibodies in 50% of the patients at doses greater than or equal to 40 mg; the expense of the antibody; and the fact that better results are currently attainable by other less expensive imaging modalities. If and when a more suitable antibody or fragment is developed, the prospect of improved staging and new treatments using immunologic conjugates carrying therapeutic agents may become realities. Until such time, prostatic cancer will be staged with other currently available imaging modalities and conventional therapies with their limitations will remain state of the art. 56 references.

  16. Chemotherapy in Prostate Cancer.

    PubMed

    Hurwitz, Michael

    2015-10-01

    For approximately a decade, chemotherapy has been shown to prolong life in patients with metastatic castration-resistant prostate cancer (mCRPC). Since that time, however, only two agents have proven to prolong life (docetaxel and cabazitaxel). However, in the last year, the addition of chemotherapy to primary hormonal therapy became a standard of care for high-volume castration-sensitive metastatic disease. Here I will review current prostate cancer chemotherapies, mechanisms of resistance to those therapies, and ongoing clinical studies of chemotherapy combinations and novel chemotherapeutics. PMID:26216506

  17. Prostate Cancer: Take Time to Decide

    MedlinePlus

    ... printing [PDF-983KB] Cancer Home Prostate Cancer: Take Time to Decide Infographic Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Prostate Cancer: Take Time to Decide Most prostate cancers grow slowly, and ...

  18. [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

  19. 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

  20. 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...

  1. 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 ( ...

  2. Survival in prostate cancer prevention trial detailed

    Cancer.gov

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

  3. Prostate 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

  4. Hepcidin regulation in prostate and its disruption in prostate cancer

    PubMed Central

    Tesfay, Lia; Clausen, Kathryn A.; Kim, Jin W.; Hegde, Poornima; Wang, Xiaohong; Miller, Lance D.; Deng, Zhiyong; Blanchette, Nicole; Arvedson, Tara; Miranti, Cindy K.; Babitt, Jodie L.; Lin, Herbert Y.; Peehl, Donna M.; Torti, Frank M.; Torti, Suzy V.

    2015-01-01

    Hepcidin is a circulating peptide hormone made by the liver that is a central regulator of systemic iron uptake and recycling. Here we report that prostate epithelial cells also synthesize hepcidin, and that synthesis and secretion of hepcidin are markedly increased in prostate cancer cells and tissue. Prostatic hepcidin functions as an autocrine hormone, decreasing cell surface ferroportin, an iron exporter, increasing intracellular iron retention, and promoting prostate cancer cell survival. Synthesis of hepcidin in prostate cancer is controlled by a unique intersection of pathways that involves BMP4/7, IL6, Wnt, and the dual BMP and Wnt antagonist, SOSTDC1. Epigenetic silencing of SOSTDC1 through methylation is increased in prostate cancer, and is associated with accelerated disease progression in prostate cancer patients. These results establish a new connection between iron metabolism and prostate cancer, and suggest that prostatic dysregulation of hepcidin contributes to prostate cancer growth and progression. PMID:25858146

  5. 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

  6. Biomarkers for prostate cancer.

    PubMed

    Schiffer, Eric

    2007-12-01

    Novel biomarkers for prostate cancer (PCa) are currently being assessed for utility in PCa diagnosis. This article aims to provide concise information on the current findings that impact prostate cancer research. Results of enzyme-linked immunosorbent assays (ELISA) for single biomarkers, quantitative polymerase chain reaction (PCR)-based assays for DNA/RNA markers will be reviewed in addition to high-throughput proteomic profiling of PCa specimens. The advantages/disadvantages of tissue, blood, urine or seminal plasma as sources for potential biomarkers are discussed emphasizing the consequences for PCa diagnosis. In summary, the majority of promising marker candidates available today needs further validation. Some of the identified markers have the potential to yield novel prognostic tools for PCa, provide novel insights into its pathophysiology, and contribute to the establishment of novel treatment strategies. PMID:17690889

  7. [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

  8. Prostate Cancer MR Imaging

    NASA Astrophysics Data System (ADS)

    Fütterer, Jurgen J.

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

  9. Biochip analysis of prostate cancer.

    PubMed

    Fan, M Q; Wang, P X; Feng, J Y; Xiao, Y; Huang, C B

    2014-01-01

    Microarray expression analysis was used to forecast the roles of differentially co-expressed genes (DCG) and DCG and links in the pathogenesis of prostate cancer. In addition, we demonstrate that the relationship between transcriptional factors (TFs) and their targets can be considered a key factor in determining the difference between primary and metastatic prostate cancer. Regulatory impact factors were adopted to calculate the impact of TF. We identified 5 TFs and 29 target genes important in the transition between normal prostate and primary prostate cancer and 2 TFs and 7 target genes important in the transition between primary and metastatic prostate cancer. These results suggest that it may be possible to predict the clinical behavior of prostate cancer based on gene expression analysis. PMID:24446298

  10. 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

  11. 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

  12. Prostate Cancer and Sexual Function

    PubMed Central

    2012-01-01

    Prostate cancer is now ranked fifth in incidence among cancers in Korean adult males. This is attributable to the more Westernized dietary style which increases the morbidity of prostate cancer and the development of cancer diagnostic technologies, such as prostate-specific antigen and advanced medical systems, increasing the rate of prostate cancer diagnosis. Prostate cancer effects include not only erectile dysfunction caused by the disease itself, but also by psychiatric disorders caused by prostate cancer or its treatments. Prostate cancer by itself reduces sexual desire and the frequency of sexual intercourse. Additionally, surgery or hormonal therapy to block testosterone further increases the frequency of erectile dysfunction. Erectile dysfunction following radical prostatectomy is primarily attributable to nerve injury caused by intraoperative nerve traction, thermal injury, ischemic injury, and local inflammatory reactions. Additionally, the absence of nocturnal penile tumescence causes persistent hypoxia of the corpus cavernosum, which, secondarily, causes anatomical and functional changes in the corpus cavernosum. Preservation of erectile function is one of the most significant issues for patients with local prostate cancer. Erectile dysfunction following radical prostatectomy is known to have various prognoses, depending on preservation of the neurovascular bundle, patient age, and preoperative erectile status. Intracavernosal injections, PDE5 inhibitors, and penile rehabilitation therapy using a vacuum constriction device after radical prostatectomy are known to improve the recovery of erectile function. Recently, testosterone replacement therapy has also drawn attention as a treatment method. PMID:23596596

  13. 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...

  14. Androgen Control in Prostate Cancer.

    PubMed

    Pelekanou, Vasiliki; Castanas, Elias

    2016-10-01

    Research on prostate cancer has extensively advanced in the past decade, through an improved understanding for its genetic basis and risk-stratification. Molecular classification of prostate cancer into distinct subtypes and the recognition of new histologic entities promise the development of tailored-made management strategies of patients. Nowadays, various alternatives are available for clinical management of localized disease ranging from observation alone through radical prostatectomy. In patients with castration-resistant prostate cancer, the approval of new drugs for the management of metastatic disease has offered promising results improving the survival of these patients. In this context, androgen receptors (AR) remain at the epicenter of prostate cancer research holding a prominent role in the biology and therapeutic regimens of prostate cancer. As many of castration-resistant tumors retain hormone-responsiveness, AR is a clinical relevant, druggable target. However, AR paradoxically remains neglected as a prostate cancer biomarker. The great advancements in prostate cancer preclinical and clinical research, imply further improvement in clinical and translational data, for patient selection and treatment optimization. For a precision medicine-guided clinical management of prostate cancer, AR evaluation has to be implemented in companion and complementary diagnostics, as discussed here. J. Cell. Biochem. 117: 2224-2234, 2016. © 2016 Wiley Periodicals, Inc. PMID:27104784

  15. 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

  16. American Cancer Society Recommendations for Prostate Cancer Early Detection

    MedlinePlus

    ... Research Get Involved Find Local ACS Learn About Cancer » Prostate Cancer » More Information » Prostate Cancer Early Detection » American ... Causes Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate Cancer Skin Cancer Show All Cancer Types News ...

  17. The link between benign prostatic hyperplasia and prostate cancer.

    PubMed

    Ørsted, David D; Bojesen, Stig E

    2013-01-01

    Benign prostatic hyperplasia (BPH) and prostate cancer are among the most common diseases of the prostate gland and represent significant burdens for patients and health-care systems in many countries. The two diseases share traits such as hormone-dependent growth and response to antiandrogen therapy. Furthermore, risk factors such as prostate inflammation and metabolic disruption have key roles in the development of both diseases. Despite these commonalities, BPH and prostate cancer exhibit important differences in terms of histology and localization. Although large-scale epidemiological studies have shown that men with BPH have an increased risk of prostate cancer and prostate-cancer-related mortality, it remains unclear whether this association reflects a causal link, shared risk factors or pathophysiological mechanisms, or detection bias upon statistical analysis. Establishing BPH as a causal factor for prostate cancer development could improve the accuracy of prognostication and expedite intervention, potentially reducing the number of men who die from prostate cancer. PMID:23165396

  18. Lactase persistence, dietary intake of milk, and the risk for prostate cancer in Sweden and Finland.

    PubMed

    Torniainen, Suvi; Hedelin, Maria; Autio, Ville; Rasinperä, Heli; Bälter, Katarina Augustsson; Klint, Asa; Bellocco, Rino; Wiklund, Fredrik; Stattin, Pär; Ikonen, Tarja; Tammela, Teuvo L J; Schleutker, Johanna; Grönberg, Henrik; Järvelä, Irma

    2007-05-01

    Prostate carcinoma is the most common cancer in men. Its primary pathogenesis is mostly unknown. Dairy products containing lactose have been suggested to be risk factors for prostate cancer. Digestion of lactose is dependent on lactase activity in the intestinal wall. A single nucleotide polymorphism C to T residing 13,910 bp upstream of the lactase gene has been shown to associate with the developmental down-regulation of lactase activity underlying persistence/nonpersistence trait. To find out whether lactase persistence is related to the risk for prostate cancer, we genotyped 1,229 Finnish and 2,924 Swedish patients and their 473 Finnish and 1,842 Swedish controls using solid-phase minisequencing. To explore if dairy products have an association with prostate cancer, we analyzed the milk consumption in the Swedish study consisting of 1,499 prostate cancer patients and 1,130 controls (Cancer Prostate in Sweden I study) using a questionnaire. Only the consumption of low-fat milk was found to be associated with increased risk of prostate cancer [odds ratio (OR), 1.73; 95% confidence interval (95% CI), 1.16-2.39]. A statistically significantly higher (P < 0.01) lactose intake was observed among subjects with high lactase activity (C/T and T/T genotypes) compared with those with low lactase activity (C/C genotype). Lactase persistence did not associate with increased risk for prostate carcinoma in the Finnish (OR, 1.11; 95% CI, 0.83-1.47; P = 0.488) or in the Swedish populations (OR, 1.16; 95% CI, 0.91-1.46; P = 0.23). In conclusion, lactase persistence/nonpersistence contains no risk for prostate cancer. Analysis of different milk products showed some evidence for low-fat milk as a potential risk factor for prostate cancer. PMID:17507622

  19. Dietary acrylamide intake and the risk of cancer among Finnish male smokers

    PubMed Central

    Hirvonen, T; Kontto, J; Jestoi, M; Valsta, L; Peltonen, K; Pietinen, P; Virtanen, SM; Sinkko, H; Kronberg-Kippilä, C; Albanes, D; Virtamo, J

    2012-01-01

    Objective To assess the association between dietary acrylamide intake and the risk of cancer among male smokers. Methods The study consisted of 27,111 male smokers, aged 50–69 years, without history of cancer. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire and a questionnaire on general background characteristics (including smoking habits) at baseline. Incident cases of cancer were identified through the national Finnish Cancer Registry. Results During an average 10.2 year follow-up 1703 lung cancers, 799 prostate cancers, 365 urothelial cancers, 316 colorectal cancers, 224 stomach cancers, 192 pancreatic cancers, 184 renal cell cancers, and 175 lymphomas were diagnosed. Dietary acrylamide intake was positively associated with the risk of lung cancer; relative risk (RR) in the highest vs. the lowest quintile in the multivariate-adjusted model was 1.18 ((95% confidence interval (CI) 1.01–1.38, p for trend 0.11). Other cancers were not associated with acrylamide intake. Conclusions High acrylamide intake is associated with increased risk of lung cancer but not with other cancers in male smokers. PMID:20859673

  20. Human Prostate Cancer Hallmarks Map.

    PubMed

    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. 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

  2. Prostate Cancer for the Internist

    PubMed Central

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

    2015-01-01

    In the United States, approximately 240,000 men are diagnosed annually with prostate cancer. Although effective treatment options are available for clinically localized cancer, the potential burdensome co-morbidities and attendant healthcare costs from over diagnosis and over treatment have escalated the discussion and controversy regarding appropriate screening, diagnosis, and optimal management of prostate cancer. Although the lifetime risk of developing prostate cancer is approximately 1 in 6 (~16%), the risk of dying from the disease is only ~2%. The discrepancy between the cancer incidence and lethality has led to widespread scrutiny of prostate cancer patient management, particularly for low-grade, low-stage (indolent) disease. The vast majority of men diagnosed with clinically localized prostate cancer are treated with interventional therapies despite studies demonstrating that even without treatment, prostate cancer-specific mortality is low. A MedLine/PubMed search was performed using PICO format (Patient, Intervention, Comparison and Outcome) identifying all relevant articles. No restrictions were used for publication dates. The terms “Prostate Cancer”, “Screening”, “Mortality”, “Morbidity” yielded 307 results. “Diagnosis”, “Prognosis” and “Survival” yielded 1504 results. Further filters were applied to narrow down the results using keywords “Prostate cancer screening guidelines 2014”, “Beyond PSA”, “NCCN Guidelines prostate”, “MRI guided Prostate biopsy” yielding 72, 274, 54 and 568 results respectively. Of these, approximately 137 articles were found relevant and were reviewed. References from the reviewed articles were included in the final article. PMID:26713287

  3. Cancer of the prostate.

    PubMed Central

    Dearnaley, D. P.

    1994-01-01

    Prostate cancer presents a growing health problem in Western societies as longevity increases. It is characteristically a disease of elderly men associated with the development of osteoblastic bone metastases and initial hormone responsiveness to androgen deprivation. Previously regarded as a Cinderella of cancers, there is currently more controversy concerning the detection and management of both localised and metastatic disease than for any other common malignancy. A balance needs to be drawn between the potential gains of more aggressive management and the disadvantages in terms of increased treatment side effects and cost, taking into account both the natural course of the disease and the life expectancy of patients. Images FIG 1 FIG 2 PMID:8142838

  4. 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

  5. Contemporary Management of Prostate Cancer.

    PubMed

    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

  6. Prevention and early detection of prostate cancer.

    PubMed

    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

    2014-10-01

    Prostate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by prostate-specific antigen (PSA) screening is controversial, but changes in the PSA threshold, frequency of screening, and the use of other biomarkers have the potential to minimise the overdiagnosis associated with PSA screening. Several new biomarkers for individuals with raised PSA concentrations or those diagnosed with prostate cancer are likely to identify individuals who can be spared aggressive treatment. Several pharmacological agents such as 5α-reductase inhibitors and aspirin could prevent development of prostate cancer. In this Review, we discuss the present 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

  7. Molecular Imaging of Prostate Cancer

    PubMed Central

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

    2015-01-01

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

  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. 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

  10. Lycopene: redress for prostate cancer.

    PubMed

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

    2012-03-01

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

  11. Lipid metabolism in prostate cancer

    PubMed Central

    Wu, Xinyu; Daniels, Garrett; Lee, Peng; Monaco, Marie E

    2014-01-01

    The malignant transformation of cells requires adaptations across multiple metabolic processes to satisfy the energy required for their increased rate of proliferation. Dysregulation of lipid metabolism has been a hallmark of the malignant phenotype; increased lipid accumulation secondary to changes in the levels of a variety of lipid metabolic enzymes has been documented in a variety of tumors, including prostate. Alterations in prostate lipid metabolism include upregulation of several lipogenic enzymes as well as of enzymes that function to oxidize fatty acids as an energy source. Cholesterol metabolism and phospholipid metabolism are also affected. With respect to lipogenesis, most studies have concentrated on increased expression and activity ofthe de novo fatty acid synthesis enzyme, fatty acid synthase (FASN), with suggestions that FASN might function as an oncogene. A central role for fatty acid oxidation in supplying energy to the prostate cancer cell is supported by the observation that the peroxisomal enzyme, α-methylacyl-CoA racemase (AMACR), which facilitates the transformation of branched chain fatty acids to a form suitable for β-oxidation, is highly overexpressed in prostate cancer compared with normal prostate. Exploitation of the alterations in lipid metabolic pathways in prostate cancer could result in the development of new therapeutic modalities as well as provide candidates for new prognostic and predictive biomarkers. AMACR has already proven to be a valuable biomarker in distinguishing normal from malignant prostate tissue, and is used routinely in clinical practice. PMID:25374912

  12. Height and Prostate Cancer Risk

    PubMed Central

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

    2008-01-01

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

  13. 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- ...

  14. Vitamin D in Prostate Cancer.

    PubMed

    Ahn, Jungmi; Park, Sulgi; Zuniga, Baltazar; Bera, Alakesh; Song, Chung Seog; Chatterjee, Bandana

    2016-01-01

    Metastatic castration-resistant prostate cancer (mCRPC) is a progressive, noncurable disease induced by androgen receptor (AR) upon its activation by tumor tissue androgen, which is generated from adrenal steroid dehydroepiandrosterone (DHEA) through intracrine androgen biosynthesis. Inhibition of mCRPC and early-stage, androgen-dependent prostate cancer by calcitriol, the bioactive vitamin D3 metabolite, is amply documented in cell culture and animal studies. However, clinical trials of calcitriol or synthetic analogs are inconclusive, although encouraging results have recently emerged from pilot studies showing efficacy of a safe-dose vitamin D3 supplementation in reducing tumor tissue inflammation and progression of low-grade prostate cancer. Vitamin D-mediated inhibition of normal and malignant prostate cells is caused by diverse mechanisms including G1/S cell cycle arrest, apoptosis, prodifferentiation gene expression changes, and suppressed angiogenesis and cell migration. Biological effects of vitamin D are mediated by altered expression of a gene network regulated by the vitamin D receptor (VDR), which is a multidomain, ligand-inducible transcription factor similar to AR and other nuclear receptors. AR-VDR cross talk modulates androgen metabolism in prostate cancer cells. Androgen inhibits vitamin D-mediated induction of CYP24A1, the calcitriol-degrading enzyme, while vitamin D promotes androgen inactivation by inducing phase I monooxygenases (e.g., CYP3A4) and phase II transferases (e.g., SULT2B1b, a DHEA-sulfotransferase). CYP3A4 and SULT2B1b levels are markedly reduced and CYP24A1 is overexpressed in advanced prostate cancer. In future trials, combining low-calcemic, potent next-generation calcitriol analogs with CYP24A1 inhibition or androgen supplementation, or cancer stem cell suppression by a phytonutrient such as sulfarophane, may prove fruitful in prostate cancer prevention and treatment. PMID:26827958

  15. Cancer incidence among Finnish ferrochromium and stainless steel production workers in 1967–2011: a cohort study

    PubMed Central

    Huvinen, Markku; Pukkala, Eero

    2013-01-01

    Objectives The aim of the study was to assess the risk of cancer among workers employed in the Finnish ferrochromium and stainless steel industry since the beginning of production in 1967. Methods The study cohort was made up of all persons employed by the Finnish stainless steel production chain from chromite mining to cold rolling of stainless steel during the period 1967–2004, and it was divided into subcohorts by production units with specific exposure patterns of the subcohorts assessed in previous studies. Follow-up for cancer through the files of the Finnish Cancer Registry was performed using the personal identity code as key. Standardised incidence ratios (SIRs) were calculated as the ratios of observed numbers of cancer cases and numbers expected on the basis of incidence rates in the population of the same region. Results The overall cancer incidence was at the expected level. The lung cancer risk was decreased in the whole cohort (SIR 0.79; 95% CI 0.65 to 1.08). The incidence of prostate cancer was significantly increased (1.31; 1.05 to 1.61) and that for kidney cancer was significantly decreased (0.38; 0.14 to 0.82). None of the department-specific SIRs for lung cancer were significantly different from 1.0. No cancers of the nose and nasal sinuses were observed among workers in the ferrochromium smelter or the stainless steel melting shop. Conclusions It is not likely that the occupational exposures in the Finnish ferrochromium and stainless steel industry would have increased the risk of cancer. PMID:24253032

  16. 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

  17. 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. PMID:26621054

  18. Prostate-specific antigen-negative prostate cancer recurrence?

    PubMed

    Froehner, Michael; Abolmaali, Nasreddin; Wirth, Manfred P

    2013-02-01

    We describe a patient with bone metastases occurring shortly after radical prostatectomy for organ-confined prostate cancer. The medical history and immunohistochemical findings suggested prostate cancer recurrence to the skeleton. Undetectable serum prostate-specific antigen levels, however, raised doubts about this diagnosis. A whole body (18)F-fluorodeoxyglucose positron emission tomography-computed tomography scan was obtained and revealed a right-sided breast cancer as the primary site of metastatic spread. PMID:23374851

  19. 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.

  20. 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.…

  1. 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 ...

  2. Prostate cancer in the elderly.

    PubMed

    Konstantinos, Hatzimouratidis

    2005-01-01

    Prostate cancer is the second leading cause of cancer deaths among men. Despite earlier diagnosis due to prostate specific antigen (PSA) screening, it is still a disease of the elderly. Diagnosis is based on digital rectal examination (DRE) and PSA assessment. Refinements in PSA testing (age-specific reference ranges, free PSA, PSA density and velocity) increased specificity and limited unnecessary prostate biopsies. Diagnosis in earlier stages (T1 and T2) commonly leads to cure with current treatment modalities. These include radical prostatectomy, external beam radiotherapy and brachytherapy. Other treatment options under development include cryotherapy and high-intensity focused ultrasound. Metastatic prostate cancer is incurable and treatment is based on hormonal therapy. Cytotoxic chemotherapy has only limited role in hormone-independent prostate cancer. Radioisotopes and biphosphonates may alleviate bone pain and prevent osteoporosis and pathological fractures. Follow-up is based on PSA. Prognostic factors for recurrence include stage, Gleason score, pre- and posttreatment PSA. Quality of life issues play an important role in selecting treatment, especially in the elderly due to comorbidities that may negatively affect the overall quality of life. A holistic approach is recommended addressing all quality of life issues without focus only in cancer control. PMID:16362603

  3. [Prostate cancer and chemotherapy].

    PubMed

    Gravis, Gwenaelle; Salem, Naji; Bladou, Franck; Viens, Patrice

    2007-07-01

    Androgen deprivation in patients with metastatic prostate cancer produces palliation of symptoms, PSA decrease and tumoral regression in most patients. After a brief period of disease regression lasting 18 to 24 months nearly all pts will progress to androgen independence disease (HRPC) with progressive clinical deterioration and ultimately death. Chemotherapy with mitoxantrone has been shown to palliate symptoms but did not extend survival. Two large randomized trials showed a survival benefit for pts with HRPC treated with docetaxel with a reduction risk of death by 21-24%, and significant improvement in palliation of symptoms and quality of life. New agents targeting angiogenesis, apoptosis, signal transduction pathway, used alone or in combination with docetaxel currently are under trial in an attempt to provide much needed improvements in outcome. Questions remains in suspend when and who need to be treated, earlier, in high risk as in adjuvant setting? Current data have demonstrated that neoadjuvant or adjuvant chemotherapy is relatively safe and feasible. Further investigation through prospective randomize trials is critical to define the precise role of this modality in high risk populations. PMID:17845990

  4. Signaling lansdscape of prostate cancer.

    PubMed

    Lin, X; Aslam, A; Attar, R; Yaylim, I; Qureshi, M Z; Hasnain, S; Qadir, M I; Farooqi, A A

    2016-01-01

    Research over the decades has gradually and sequentially shown that both intratumor heterogeneity and multifocality make prostate cancer difficult to target. Different challenges associated with generation of risk-stratification tools that correlate genomic landscape with clinical outcomes severely influence clinical efficacy of therapeutic strategies. Androgen receptor mediated signaling has gained great appreciation and rewiring of AR induced signaling cascade in absence of androgen, structural variants of AR have provided near complete resolution of genomic landscape and underlying mechanisms of prostate cancer. In this review we have attempted to provide an overview of most recent advancements in our knowledge related to different signaling cascades including TGF, SHH, Notch, JAK-STAT in prostate cancer progression and development. PMID:26828986

  5. Gene therapy for prostate cancer.

    PubMed

    Tangney, Mark; Ahmad, Sarfraz; Collins, Sara A; O'Sullivan, Gerald C

    2010-05-01

    Cancer remains a leading cause of morbidity and mortality. Despite advances in understanding, detection, and treatment, it accounts for almost one-fourth of all deaths per year in Western countries. Prostate cancer is currently the most commonly diagnosed noncutaneous cancer in men in Europe and the United States, accounting for 15% of all cancers in men. As life expectancy of individuals increases, it is expected that there will also be an increase in the incidence and mortality of prostate cancer. Prostate cancer may be inoperable at initial presentation, unresponsive to chemotherapy and radiotherapy, or recur following appropriate treatment. At the time of presentation, patients may already have metastases in their tissues. Preventing tumor recurrence requires systemic therapy; however, current modalities are limited by toxicity or lack of efficacy. For patients with such metastatic cancers, the development of alternative therapies is essential. Gene therapy is a realistic prospect for the treatment of prostate and other cancers, and involves the delivery of genetic information to the patient to facilitate the production of therapeutic proteins. Therapeutics can act directly (eg, by inducing tumor cells to produce cytotoxic agents) or indirectly by upregulating the immune system to efficiently target tumor cells or by destroying the tumor's vasculature. However, technological difficulties must be addressed before an efficient and safe gene medicine is achieved (primarily by developing a means of delivering genes to the target cells or tissue safely and efficiently). A wealth of research has been carried out over the past 20 years, involving various strategies for the treatment of prostate cancer at preclinical and clinical trial levels. The therapeutic efficacy observed with many of these approaches in patients indicates that these treatment modalities will serve as an important component of urological malignancy treatment in the clinic, either in isolation or

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

    PubMed Central

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

    2015-01-01

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

  7. Prostate cancer immunotherapy: beyond immunity to curability.

    PubMed

    Simons, Jonathan W

    2014-11-01

    Metastatic prostate cancer is the second leading cause of death from cancer in the United States. It is the first prevalent cancer in which overall survival in advanced disease is modestly, but objectively, improved with outpatient delivered dendritic cell-based immunotherapy. More prostate cancer patients have enrolled through Facebook and trusted-site Internet searches in clinical trials for prostate cancer vaccine-based immunotherapy than in immunotherapy trials for lung, breast, colon, pancreas, ovarian, and bladder cancer combined in the past 7 years. Exceptional responses to anti-CTLA-4 treatment have been documented in clinics, and prostate cancer neoantigen characterization and T-cell clonotyping are in their research ascendancy. The prostate is an accessory organ; it is not required for fertility, erectile function, or urinary continence. The true evolutionary advantage of having a prostate for male mammalian physiology is a topic of speculation in seminar rooms and on bar stools, but it remains unknown. Hundreds of prostate lineage-unique proteins (PLUP) exist among the >37,000 normal human prostate lineage-unique open reading frames that can be targeted for immunologic ablation of PLUP(+) prostate cancer cells by prostate-specific autoimmunity. This bioengineered graft-versus-prostate disease is a powerful strategy that can eliminate deaths from prostate cancer. Immunologic tolerance to prostate cancer can be overcome at every clinical stage of presentation. This Cancer Immunology at the Crossroads article aims to present advances in the past two decades of basic, translational, and clinical research in prostate cancer, including bioengineering B-cell and T-cell responses, and ongoing prostate cancer immunotherapy trials. PMID:25367978

  8. 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 ...

  9. Prevention strategies in prostate cancer

    PubMed Central

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

    2010-01-01

    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

  10. DNA microarrays in prostate cancer.

    PubMed

    Ho, Shuk-Mei; Lau, Kin-Mang

    2002-02-01

    DNA microarray technology provides a means to examine large numbers of molecular changes related to a biological process in a high throughput manner. This review discusses plausible utilities of this technology in prostate cancer research, including definition of prostate cancer predisposition, global profiling of gene expression patterns associated with cancer initiation and progression, identification of new diagnostic and prognostic markers, and discovery of novel patient classification schemes. The technology, at present, has only been explored in a limited fashion in prostate cancer research. Some hurdles to be overcome are the high cost of the technology, insufficient sample size and repeated experiments, and the inadequate use of bioinformatics. With the completion of the Human Genome Project and the advance of several highly complementary technologies, such as laser capture microdissection, unbiased RNA amplification, customized functional arrays (eg, single-nucleotide polymorphism chips), and amenable bioinformatics software, this technology will become widely used by investigators in the field. The large amount of novel, unbiased hypotheses and insights generated by this technology is expected to have a significant impact on the diagnosis, treatment, and prevention of prostate cancer. Finally, this review emphasizes existing, but currently underutilized, data-mining tools, such as multivariate statistical analyses, neural networking, and machine learning techniques, to stimulate wider usage. PMID:12084220

  11. 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

  12. 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.

  13. Common Gene Rearrangements in Prostate Cancer

    PubMed Central

    Rubin, Mark A.; Maher, Christopher A.; Chinnaiyan, Arul M.

    2011-01-01

    Prostate cancer is a common heterogeneous disease, and most patients diagnosed in the post prostate-specific antigen (PSA) era present with clinically localized disease, the majority of which do well regardless of treatment regimen undertaken. Overall, those with advanced prostate cancer at time of diagnosis do poorly after androgen withdrawal therapy. Understanding the biologic underpinning of prostate cancer is necessary to best determine the risk of disease progression and would be advantageous for the development of novel therapeutic approaches to impede or prevent disease. This review focuses on the recently identified common ETS and non-ETS gene rearrangements in prostate cancer. Although multiple molecular alterations have been detected in prostate cancer, a detailed understanding of gene fusion prostate cancer should help explain the clinical and biologic diversity, providing a rationale for a molecular subclassification of the disease. PMID:21859993

  14. Immunotherapy for metastatic prostate cancer

    PubMed Central

    Drake, Charles G.

    2016-01-01

    Chemotherapy with docetaxel is the standard treatment for men with metastatic prostate cancer, and results in statistically significant improvements in survival, as well as in quality of life. However, the response rate to single-agent docetaxel is approximately 40% to 45%, emphasizing a need for alternative approaches. More significantly, with the onset of early, PSA-based detection of prostate cancer and closer follow-up, many men present with metastatic disease that remains asymptomatic. For such patients, the side effects of chemotherapy would compromise their current performance status and, thus, a nontoxic, early treatment option that could improve overall survival would be highly desirable. Immunotherapy represents one such approach; a number of clinical trials have suggested a survival benefit for immunotherapy in metastatic prostate cancer and confirmed that these agents are generally well-tolerated. As is the case for chemotherapy, it is doubtful that maximal survival benefit will be achieved with single-agent immunotherapy; experimental treatments in which mechanistically distinct immunotherapy approaches are combined, as well as approaches in which immunotherapy is combined with chemotherapy or hormonal therapy are currently under investigation. This review will discuss the mechanisms of action of several immunotherapy approaches for metastatic prostate cancer, focusing on active immunotherapy as opposed to administration of anti-tumor antibodies. The relative advantages and disadvantages of current approaches will be noted, and ongoing clinical trials will be highlighted. PMID:18593624

  15. 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.

  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. 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

  19. Decision making and prostate cancer screening.

    PubMed

    Knight, Sara J

    2014-05-01

    This article presents an overview of the challenges that men encounter in making decisions about prostate cancer screening, including complex affective and cognitive factors and controversies in the interpretation of the evidence on prostate cancer screening. Shared decision making involving patient decision aids are discussed as approaches that can be used to improve the quality of prostate cancer screening decisions, including a close alignment between a man's values, goals, and preferences and his choice about screening. PMID:24725488

  20. 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

  1. 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

  2. Bone imaging in prostate cancer.

    PubMed

    Dotan, Zohar A

    2008-08-01

    Bone metastases of solid tumors are common, and about 80% of them occur in patients with breast, lung or prostate cancer. Bone metastases can be suspected clinically and by laboratory tests; however, a final diagnosis relies on radiographic evidence. Bone metastases of prostate cancer usually have osteoblastic characteristics, manifested by pathological bone resorption and formation. Conventional bone scans (e.g. with (99m)Tc-labeled methylene diphosphonate) are preferred to plain-film radiography for surveillance of the entire skeleton. Radiologic diagnosis of bone metastases, particularly in patients with low burden of disease, is difficult because noncancerous bone lesions that mimic cancer are common. Conventional bone scans are limited by their low sensitivity and high false-negative rate (up to 40%) compared with advanced bone-imaging modalities such as PET, PET-CT and MRI, which might assist or replace conventional scanning methods. The correct diagnosis of bone involvement in prostate cancer is crucial to assess the effects of therapy on the primary tumor, the patient's prognosis, and the efficacy of bone-specific treatments that can reduce future bone-associated morbidity. In addition, predictive tools such as nomograms enable the identification of patients at risk of bone involvement during the course of their disease. Such tools may limit treatment costs by avoidance of unnecessary tests and might reduce both short-term and long-term complication rates. PMID:18682719

  3. Antisense approaches in prostate cancer.

    PubMed

    Chi, Kim N; Gleave, Martin E

    2004-06-01

    Patients with hormone refractory prostate cancer have limited treatment options and new therapies are urgently needed. Advances in the understanding of the molecular mechanisms implicated in prostate cancer progression have identified many potential therapeutic gene targets that are involved in apoptosis, growth factors, cell signalling and the androgen receptor (AR). Antisense oligonucleotides are short sequences of synthetic modified DNA that are designed to be complimentary to a selected gene's mRNA and thereby specifically inhibit expression of that gene. The antisense approach continues to hold promise as a therapeutic modality to target genes involved in cancer progression, especially those in which the gene products are not amenable to small molecule inhibition or antibodies. The current status and future direction of a number of antisense oligonucleotides targeting several genes, including BCL-2, BCL-XL, clusterin, the inhibitors of apoptosis (IAP) family, MDM2, protein kinase C-alpha, c-raf, insulin-like growth factor binding proteins and the AR, that have potential clinical use in prostate cancer are reviewed. PMID:15174974

  4. 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.

  5. Prostate Cancer, Version 1.2016.

    PubMed

    Mohler, James L; Armstrong, Andrew J; Bahnson, Robert R; D'Amico, Anthony Victor; Davis, Brian J; Eastham, James A; Enke, Charles A; Farrington, Thomas A; Higano, Celestia S; Horwitz, Eric M; Hurwitz, Michael; Kane, Christopher J; Kawachi, Mark H; Kuettel, Michael; Lee, Richard J; Meeks, Joshua J; Penson, David F; Plimack, Elizabeth R; Pow-Sang, Julio M; Raben, David; Richey, Sylvia; Roach, Mack; Rosenfeld, Stan; Schaeffer, Edward; Skolarus, Ted A; Small, Eric J; Sonpavde, Guru; Srinivas, Sandy; Strope, Seth A; Tward, Jonathan; Shead, Dorothy A; Freedman-Cass, Deborah A

    2016-01-01

    The NCCN Guidelines for Prostate Cancer address staging and risk assessment after an initial diagnosis of prostate cancer and management options for localized, regional, and metastatic disease. Recommendations for disease monitoring, treatment of recurrent disease, and systemic therapy for metastatic castration-recurrent prostate cancer also are included. This article summarizes the NCCN Prostate Cancer Panel's most significant discussions for the 2016 update of the guidelines, which include refinement of risk stratification methods and new options for the treatment of men with high-risk and very-high-risk disease and progressive castration-naïve disease. PMID:26733552

  6. Toll-Like Receptors and Prostate Cancer

    PubMed Central

    Zhao, Shu; Zhang, Yifan; Zhang, Qingyuan; Wang, Fen; Zhang, Dekai

    2014-01-01

    Prostate cancer is the second leading cause of cancer-related death in men after lung cancer. Immune responses clearly play a critical role in the tumorigenesis and in the efficacy of radiation therapy and chemotherapy in prostate cancer; however, the underlying molecular mechanisms are still poorly understood. Toll-like receptors (TLRs) are a well-known family of pattern recognition receptors that play a key role in host immune system. Recent studies demonstrate that there are links between TLRs and cancer; however, the function and biological importance of TLRs in prostate cancer seems complex. To elucidate the role of TLRs and innate immunity in prostate cancer might provide us with a better understanding of the molecular mechanisms of this disease. Moreover, utilizing the agonists or antagonists of TLRs might represent a promising new strategy against prostate cancer. In this review, we summarize recent advances on the studies of association between TLR signaling and prostate cancer, TLR polymorphisms and prostate cancer risk, and provide some insights about TLRs as potential targets for prostate cancer immunotherapy. PMID:25101092

  7. 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

  8. [Medical treatment of prostate cancer].

    PubMed

    Lobel, B; Cipolla, B; Labrador, J

    1994-03-01

    Hormone dependence of prostate cancer is well known. In 80% of cases with metastases, hormone suppression leads to the reduction of tumour volume and related disorders. However the treatment is generally palliative because malignant process recurs after about around 16 months. Mean survival is less than 3 years in these forms. Lack of response come always together with a poor prognosis, and there is 90% mortality at 2 years. Advanced prostatic cancer should not be treated with hormones if the patient has few symptoms and his quality of life is satisfactory. Symptomatic forms require hormone manipulation. Orchidectomy or LH-RH are recommended. Total androgen ablation (combined treatment) leads rapidly to more relief of symptoms, but its drawbacks and especially high cost indicate that its use should be weighed individually. Estramustine is not a first-lune treatment. Presently, there is no criteria to predict response to treatment. PMID:8066398

  9. [Novel treatment for prostate cancer targeting prostaglandins].

    PubMed

    Terada, Naoki; Inoue, Takahiro; Kamba, Tomomi; Ogawa, Osamu

    2014-12-01

    PGE2 is highly expressed in the prostate, associating with prostate cancer progression. Targeting downstream signaling pathways of PGE2 may represent an attractive new strategy for the treatment of prostate cancer. We have established a novel prostate cancer xenograft model, KUCaP-2. The expression of EP4, one of PGE2 receptors, was significantly up-regulated during the development of castration resistance. A specific EP4 antagonist, ONO-AE3-208, decelerated castration-resistant growth of KUCaP-2 tumors in vivo. Moreover, ONO-AE3-208 could in vitro inhibit the cell invasion and in vivo suppress the bone metastasis of prostate cancer cells. These results indicated that EP4 is a novel target for the treatment of metastatic castration resistant prostate cancer. PMID:25518348

  10. Prostate cancer - treatment

    MedlinePlus

    ... blood in the urine There are reports of secondary cancers arising from the radiation as well. Proton therapy ... Chemotherapy and immunotherapy (medicine that helps the body's immune system fight the cancer) may be used to ...

  11. 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

  12. [Roles of folate metabolism in prostate cancer].

    PubMed

    Sun, Fei-vu; Hu, Qing-feng; Xia, Guo-wei

    2015-07-01

    Epidemiological surveys show that folic acid can prevent prostate cancer, but fortified folic acid may increase the risk of the malignancy. The physician data queries from the National Cancer Institute of the USA describe folate as protective against prostate cancer, whereas its synthetic analog, folic acid, is considered to increase prostate cancer risk when taken at levels easily achievable by eating fortified food or taking over-the-counter supplements. We review the current literature to examine the effects of folate and folic acid on prostate cancer, help interpret previous epidemiologic data, and provide a clarification regarding the apparently opposing roles of folate for patients with prostate cancer. A literature search was conducted in Medline to identify studies investigating the effect of nutrition and specifically folate and folic acid on prostate carcinogenesis and progression. In addition, the National Health and Nutrition Examination Survey database was analyzed for the trends in serum folate levels before and after mandatory fortification. Folate likely plays a dual role in prostate carcinogenesis. There remains some conflicting epidemiologic evidence regarding folate and prostate cancer risk. However, there is growing experimental evidence that higher circulating folate levels can contribute to prostate cancer progression. Further research is needed to clarify these complex relationships. PMID:26333231

  13. Precision medicine for advanced prostate cancer

    PubMed Central

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

    2016-01-01

    Purpose of review Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Recent findings Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Summary Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients. PMID:26909474

  14. Approach to Oligometastatic Prostate Cancer.

    PubMed

    Bernard, Brandon; Gershman, Boris; Karnes, R Jeffrey; Sweeney, Christopher J; Vapiwala, Neha

    2016-01-01

    Oligometastatic prostate cancer has increasingly been recognized as a unique clinical state with therapeutic implications. It has been proposed that patients with oligometastases may have a more indolent course and that outcome may be further improved with metastasis-directed local ablative therapy. In addition, there are differing schools of thoughts regarding whether oligometastases represent isolated lesions-where targeted therapy may render a patient disease free-or whether they coexist with micrometastases, where targeted therapy in addition to systemic therapy is required for maximal clinical impact. As such, the approach to the patient with oligometastatic prostate cancer requires multidisciplinary consideration, with surgery, radiotherapy, and systemic therapy potentially of benefit either singularly or in combination. Indeed, mounting evidence suggests durable disease-free intervals and, in some cases, possibly cure, may be achieved with such a multimodal strategy. However, selecting patients that may benefit most from treatment of oligometastases is an ongoing challenge. Moreover, with the advent of new, highly sensitive imaging technologies, the spectrum based on CT of the abdomen and pelvis and technetium bone scan of localized to oligometastatic to widespread disease has become increasingly blurred. As such, new MRI- and PET-based modalities require validation. As some clinical guidelines advise against routine prostate-specific antigen screening, the possibility of more men presenting with locally advanced or de novo oligometastatic prostate cancer exists; thus, knowing how best to treat these patients may become more relevant at a population level. Ultimately, the arrival of prospective clinical data and better understanding of biology will hopefully further inform how best to treat men with this disease. PMID:27249693

  15. 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

  16. Development of New Treatments for Prostate Cancer

    SciTech Connect

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

    2005-02-01

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

  17. 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

  18. 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

  19. Functional Imaging for Prostate Cancer: Therapeutic Implications

    PubMed Central

    Aparici, Carina Mari; Seo, Youngho

    2012-01-01

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

  20. 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

  1. Review of selenium and prostate cancer prevention.

    PubMed

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

    2013-01-01

    Prostate cancer is the most common malignancy in men in the United States. Surgery or radiation are sometimes unsatisfactory treatments because of the complications such as incontinence or erectile dysfunction. Selenium was found to be effective to prevent prostate cancer in the Nutritional Prevention of Cancer Trial (NPC), which motivated two other clinical trials: the Selenium and Vitamin E Cancer Prevention Trial (SELECT) and a Phase III trial of selenium to prevent prostate cancer in men with high-grade prostatic intraepithelial neoplasia. However, these two trials failed to confirm the results of the NPC trial and indicated that the selenium may not be preventive of prostate cancer. In this article we review the three clinical trials and discuss some different points which might be potential factors underlying variation in results obtained. PMID:23725109

  2. AB012. Brachytherapy for localized prostate cancer

    PubMed Central

    Xu, Yong; Yang, Yong

    2016-01-01

    Background To evaluate the security and effect of brachytherapy for localized prostate cancer. Methods Forty five patients with Tl–T2 prostate cancer were treated with real-time transperineal ultrasound-guide 125I seeds prostate implantation. Results The median operation time was 90 min, the median number of I seeds used was 56. The follow up time was 12–48 months, the cases of PSA <1 µg/L were 29, PSA 1–2 µg/L were 11 and PSA ≥2 µg/L were 5. Conclusions Brachytherapy for localized prostate cancer is safe and effective.

  3. Risk factors for skin cancer among Finnish airline cabin crew.

    PubMed

    Kojo, Katja; Helminen, Mika; Pukkala, Eero; Auvinen, Anssi

    2013-07-01

    Increased incidence of skin cancers among airline cabin crew has been reported in several studies. We evaluated whether the difference in risk factor prevalence between Finnish airline cabin crew and the general population could explain the increased incidence of skin cancers among cabin crew, and the possible contribution of estimated occupational cosmic radiation exposure. A self-administered questionnaire survey on occupational, host, and ultraviolet radiation exposure factors was conducted among female cabin crew members and females presenting the general population. The impact of occupational cosmic radiation dose was estimated in a separate nested case-control analysis among the participating cabin crew (with 9 melanoma and 35 basal cell carcinoma cases). No considerable difference in the prevalence of risk factors of skin cancer was found between the cabin crew (N = 702) and the general population subjects (N = 1007) participating the study. The mean risk score based on all the conventional skin cancer risk factors was 1.43 for cabin crew and 1.44 for general population (P = 0.24). Among the cabin crew, the estimated cumulative cosmic radiation dose was not related to the increased skin cancer risk [adjusted odds ratio (OR) = 0.75, 95% confidence interval (CI): 0.57-1.00]. The highest plausible risk of skin cancer for estimated cosmic radiation dose was estimated as 9% per 10 mSv. The skin cancer cases had higher host characteristics scores than the non-cases among cabin crew (adjusted OR = 1.43, 95% CI: 1.01-2.04). Our results indicate no difference between the female cabin crew and the general female population in the prevalence of factors generally associated with incidence of skin cancer. Exposure to cosmic radiation did not explain the excess of skin cancer among the studied cabin crew in this study. PMID:23316078

  4. 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

  5. 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

  6. MedlinePlus: Prostate Cancer Screening

    MedlinePlus

    ... Cancer (U.S. Preventive Services Task Force) - PDF Specifics Digital Rectal Exam (DRE) (American Society of Clinical Oncology) Prostate Cancer Screening: Should You Get a PSA Test? (Mayo Foundation for Medical Education and Research) Prostate-Specific Antigen (PSA) Test (National ...

  7. A history of prostate cancer treatment

    PubMed Central

    Denmeade, Samuel R.; Isaacs, John T.

    2014-01-01

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

  8. 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 ...

  9. 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

  10. 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

  11. Epidemiology of Prostate and Testicular Cancer.

    PubMed

    Filippou, Pauline; Ferguson, James E; Nielsen, Matthew E

    2016-09-01

    Prostate and testicular cancers account for a large percentage of cancer morbidity in men in the United States and worldwide due to high prevalence rates that continue to grow. Patterns of incidence and mortality vary greatly in both cancers among men of different age groups, ethnicities, and geographic locations. This article summarizes the incidence, prognosis, and risk factors of both prostate and testicular cancers, globally and in the United States. PMID:27582605

  12. Prostate cancer progression. Implications of histopathology.

    PubMed Central

    Ware, J. L.

    1994-01-01

    This review examines selected areas of contemporary prostate cancer research in terms of the impact of prostatic cellular and histopathological heterogeneity. Prostate tumor progression is accompanied by dysregulation of multiple growth factor networks as well as disruption of normal patterns of cell-cell interactions. Molecular and cytogenetic studies demonstrate that prostate cancer results from the accumulation of several different genetic defects. No single event predominates, but modifications in tumor suppressor genes or functional elimination of the suppressor gene product are more common than activation of known oncogenes. Intratumor heterogeneity is also detectable at the genetic level. This further complicates efforts to correlate modifications at specific loci with progression or outcome. The development of new in vitro and in vivo systems for the study of human prostate cancer should increase our understanding of this complex disease. In each approach, knowledge of the histopathology of the normal and neoplastic prostate is essential. PMID:7977655

  13. Opposing roles of folate in prostate cancer.

    PubMed

    Rycyna, Kevin J; Bacich, Dean J; O'Keefe, Denise S

    2013-12-01

    The US diet has been fortified with folic acid to prevent neural tube defects since 1998. The Physician Data Queries from the National Cancer Institute describe folate as protective against prostate cancer, whereas its synthetic analog, folic acid, is considered to increase prostate cancer risk when taken at levels easily achievable by eating fortified food or taking over-the-counter supplements. We review the present literature to examine the effects of folate and folic acid on prostate cancer, help interpret previous epidemiologic data, and provide clarification regarding the apparently opposing roles of folate for patients with prostate cancer. A literature search was conducted in Medline to identify studies investigating the effect of nutrition and specifically folate and folic acid on prostate carcinogenesis and progression. In addition, the National Health and Nutrition Examination Survey database was analyzed for trends in serum folate levels before and after mandatory fortification. Folate likely plays a dual role in prostate carcinogenesis. There remains conflicting epidemiologic evidence regarding folate and prostate cancer risk; however, there is growing experimental evidence that higher circulating folate levels can contribute to prostate cancer progression. Further research is needed to clarify these complex relationships. PMID:23992971

  14. 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

  15. The Japanese guideline for prostate cancer screening.

    PubMed

    Hamashima, Chisato; Nakayama, Tomio; Sagawa, Motoyasu; Saito, Hiroshi; Sobue, Tomotaka

    2009-06-01

    In 2005, there were 9264 deaths from prostate cancer, accounting for 4.7% of the total number of cancer deaths in Japan. As the population continues to age, interest in prostate cancer screening has increased, and opportunistic screening for prostate cancer has been conducted worldwide. The guideline for prostate cancer screening was developed based on the established method. The efficacies of prostate-specific antigen (PSA) and digital rectal examination (DRE) were evaluated. Based on the balance of the benefits and harms, recommendations for population-based and opportunistic screening were formulated. Two methods of prostate cancer screening were evaluated. Based on the analytic framework involving key questions, 1186 articles published from January 1985 to October 2006 were selected using MEDLINE and other methods. After the systematic literature review, 28 articles were identified as providing evidence of mortality reduction from prostate cancer, including 5 observational studies for DRE screening, 1 meta-analysis, 3 randomized controlled trials and 19 observational studies for PSA screening. Although several studies showed that PSA screening had a beneficial effect, the results of the selected studies were inconsistent. Overall, the evidence that screening reduced mortality from prostate cancer was insufficient. Furthermore, prostate cancer screening is associated with serious harms, including overdiagnosis, adverse effects of needle biopsy and adverse effects of local prostatectomy. At present, the evidence for the effect of prostate cancer screening is insufficient. Both PSA and DRE were not recommended for population-based screening programs, but they could be conducted as individual-based screening if basic requirements were met. PMID:19346535

  16. Serum and dietary vitamin E in relation to prostate cancer risk.

    PubMed

    Weinstein, Stephanie J; Wright, Margaret E; Lawson, Karla A; Snyder, Kirk; Männistö, Satu; Taylor, Philip R; Virtamo, Jarmo; Albanes, Demetrius

    2007-06-01

    Alpha-tocopherol supplementation (50 mg daily for 5-8 years) reduced prostate cancer incidence by 32% in the alpha-Tocopherol, beta-Carotene Cancer Prevention Study. We investigated whether serum alpha-tocopherol or intake of vitamin E (eight tocopherols and tocotrienols) was associated with prostate cancer risk with up to 19 years of follow-up in the alpha-Tocopherol, beta-Carotene Cancer Prevention Study cohort. Of the 29,133 Finnish male smokers, ages 50 to 69 years recruited into the study, 1,732 were diagnosed with incident prostate cancer between 1985 and 2004. Baseline serum alpha-tocopherol was measured by high-performance liquid chromatography and the components of vitamin E intake were estimated based on a 276-item food frequency questionnaire and food chemistry analyses. Proportional hazard models were used to determine multivariate-adjusted relative risks (RR) and 95% confidence intervals (95% CI). Higher serum alpha-tocopherol was associated with reduced risk of prostate cancer (RR, 0.80; 95% CI, 0.66-0.96 for highest versus lowest quintile; Ptrend = 0.03) and was strongly and inversely related to the risk of developing advanced disease (RR, 0.56; 95% CI, 0.36-0.85; Ptrend = 0.002). The inverse serum alpha-tocopherol-prostate cancer association was greater among those who were supplemented with either alpha-tocopherol or beta-carotene during the trial. There were no associations between prostate cancer and the individual dietary tocopherols and tocotrienols. In summary, higher prediagnostic serum concentrations of alpha-tocopherol, but not dietary vitamin E, was associated with lower risk of developing prostate cancer, particularly advanced prostate cancer. PMID:17548693

  17. 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

  18. 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

  19. [Prostate cancer and metabolic syndrome].

    PubMed

    Nagamatsu, Hirotaka; Teishima, Jun; Inoue, Shogo; Hayashi, Tetsutaro; Matsubara, Akio

    2016-01-01

    The prevalence of metabolic syndrome (MS) is increasing in Japan because of westernization of diet and lifestyle. Previous epidemiological studies have demonstrated MS to relate with the malignant potential of prostate cancer (PCa) while its relationship to the risk of PCa has been still controversial. Several pathologies involved in MS, such as insulin resistance, abnormality of secreted adipokines, chronic inflammation, alteration of sex hormones, have been reported to affect the progression of PCa. Based on these evidences, clinical studies for PCa patients have been tried for suppressing the progression of PCa through the management of MS. PMID:26793896

  20. 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

  1. Is prostate cancer screening responsible for the negative results of prostate cancer treatment trials?

    PubMed

    Prasad, Vinay

    2016-08-01

    Clinical guidelines continue to move away from routine prostate specific antigen screening (PSA), once a widespread medical practice. A curious difference exists between early prostate cancer and early breast cancer. While randomized trials of therapy in early breast cancer continue to show overall survival benefit, this is not the case in prostate cancer, where prostatectomy was no better than observation in a recent trial, and where early androgen deprivation is no better than late androgen deprivation. Here, I make the case that prostate cancer screening contributes so greatly to over diagnosis that even treatment trials yield null results due to contamination with non-life threatening disease. PMID:27372859

  2. 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

  3. Comparison of different prostatic markers in lymph node and distant metastases of prostate cancer.

    PubMed

    Queisser, Angela; Hagedorn, Susanne A; Braun, Martin; Vogel, Wenzel; Duensing, Stefan; Perner, Sven

    2015-01-01

    Prostate cancer is mostly diagnosed at an early stage; however, some tumors are diagnosed in a metastatic stage as cancer of unknown primary origin. In order to allow specific treatment in the case of prostate cancer presenting as cancer of unknown primary origin, it is important to determine the tumor origin. Prostate-specific antigen is used as a diagnostic marker for prostate cancer but the expression declines with progression to castration-resistant prostate cancer. Aim of this study was to identify the most informative marker constellation, which is able to detect metastatic prostate cancer at high sensitivity. The widely used prostate cancer markers such as prostate-specific antigen, prostate-specific acid phosphatase, androgen receptor, prostate-specific membrane antigen, prostein, and ETS-related gene were investigated for their sensitivity to detect prostatic origin of metastases. Expression of prostate-specific antigen, prostate-specific acid phosphatase, androgen receptor, prostate-specific membrane antigen, prostein, and ETS-related gene was determined on archived tissue specimens consisting of benign prostatic tissue (n=9), primary prostate cancer (n=79), lymph node metastases (n=58), and distant metastases (n=39) using immunohistochemistry. The staining intensity was categorized as negative (0), weak (1), moderate (2), and strong (3). All markers except ETS-related gene were able to detect at least 70% of lymph node metastases and distant metastases, with prostate-specific antigen, androgen receptor, and prostate-specific membrane antigen having the highest sensitivity (97%, 91%, and 94%, respectively). A further increase of the sensitivity up to 98% and 100% could be achieved by the combination of prostate-specific antigen, prostate-specific membrane antigen, or androgen receptor for lymph node metastases and for distant metastases, respectively. The same sensitivity could be reached by combining prostate-specific membrane antigen and prostein. Our

  4. 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

  5. [Treatment strategies for advanced prostate cancer].

    PubMed

    Küronya, Zsófia; Bíró, Krisztina; Géczi, Lajos; Németh, Hajnalka

    2015-09-01

    There has been dramatic improvement in the diagnosis and treatment of prostate cancer recently. The treatment of localized disease became more successful with the application of new, sophisticated techniques available for urologic surgeons and radiotherapists. Nevertheless a significant proportion of patients relapses after the initial local treatment or is diagnosed with metastatic disease at the beginning. In the past five years, six new drugs became registered for the treatment of metastatic, castration-resistant prostate cancer, such as sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, the α-emitting radionuclide alpharadin and the receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor denosumab. The availability of these new treatment options raises numerous questions. In this review we present the standard of care of metastatic prostate cancer by disease stage (hormone naive/ hormone sensitive metastatic prostate cancer, non-metastatic castration-resistant prostate cancer, oligometastatic/multimetastatic castration-resistant prostate cancer) and the emerging treatment modalities presently assessed in clinical trials. We would also like to give advice on debatable aspects of the management of metastatic prostate cancer. PMID:26339912

  6. Nanotherapies for treating prostate cancer

    NASA Astrophysics Data System (ADS)

    Danquah, Michael

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

  7. 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

  8. 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

  9. Recurrent Gene Fusions in Prostate Cancer

    PubMed Central

    Kumar-Sinha, Chandan; Tomlins, Scott A.; Chinnaiyan, Arul M.

    2009-01-01

    The discovery of recurrent gene fusions in a majority of prostate cancers has important clinical and biological implications in the study of common epithelial tumors. Gene fusion and chromosomal rearrangements were previously thought to be the primary oncogenic mechanism of hematological malignancies and sarcomas. The prostate cancer gene fusions that have been identified thus far are characterized by 5’ genomic regulatory elements, most commonly controlled by androgen, fused to members of the ETS family of transcription factors, leading to the over-expression of oncogenic transcription factors. ETS gene fusions likely define a distinct class of prostate cancer which may have a bearing on diagnosis, prognosis and rational therapeutic targeting. PMID:18563191

  10. Magnetic resonance imaging of prostate cancer.

    PubMed

    Guneyli, Serkan; Erdem, Cemile Zuhal; Erdem, Lutfi Oktay

    2016-01-01

    Prostate cancer is one of the causes of cancer-related deaths. Multiparametric magnetic resonance imaging (MRI) provides the best soft tissue resolution and plays an important role in the management of prostate cancer patients. It is the recommended imaging modality for patients with prostate cancer, and it is clinically indicated for diagnosis, staging, tumor localization, detection of tumor aggressiveness, follow-up, and MRI-guided interventions. Multiparametric MRI includes T1- and high-resolution T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced MRI. We evaluated MR images of patients with prostate cancer who underwent multiparametric endorectal MRI on a 3.0-T scanner and presented demonstrative images. PMID:27317204

  11. Statin Use in Prostate Cancer: An Update

    PubMed Central

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

    2016-01-01

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

  12. 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

  13. 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

  14. 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

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

    PubMed

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

    2013-03-01

    Prostate cancer is the leading cancer type diagnosed in American men and is the second leading cancer diagnosed in men worldwide. Although studies have been conducted to investigate the association between prostate cancer and exposure to pesticides and/or farming, the results have been inconsistent. We performed a meta-analysis to summarize the association of farming and prostate cancer. The PubMed database was searched to identify all published case-control studies that evaluated farming as an occupational exposure by questionnaire or interview and prostate cancer. Ten published and two unpublished studies were included in this analysis, yielding 3,978 cases and 7,393 controls. Prostate cancer cases were almost four times more likely to be farmers compared with controls with benign prostate hyperplasia (BPH; meta odds ratio [OR], crude = 3.83, 95% confidence interval [CI] = 1.96-7.48, Q-test p value = .352; two studies); similar results were obtained when non-BPH controls were considered, but with moderate heterogeneity between studies (meta OR crude = 1.38, 95% CI = 1.16-1.64, Q-test p value = .216, I (2) = 31% [95% CI = 0-73]; five studies). Reported pesticide exposure was inversely associated with prostate cancer (meta OR crude = 0.68, 95% CI = 0.49-0.96, Q-test p value = .331; four studies), whereas no association with exposure to fertilizers was observed. Our findings confirm that farming is a risk factor for prostate cancer, but this increased risk may not be due to exposure to pesticides. PMID:22948300

  16. Molecular pathways and targets in prostate cancer

    PubMed Central

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

    2014-01-01

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

  17. 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

  18. Regular Exercise May Boost Prostate Cancer Survival

    MedlinePlus

    ... nih.gov/medlineplus/news/fullstory_158374.html Regular Exercise May Boost Prostate Cancer Survival Study found that ... HealthDay News) -- Sticking to a moderate or intense exercise regimen may improve a man's odds of surviving ...

  19. 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.

  20. Shorter, Intensive Radiation Works for Prostate Cancer

    MedlinePlus

    ... April 4, 2016 (HealthDay News) -- A slightly higher dose of radiation therapy for early stage prostate cancer may reduce treatment time without compromising effectiveness, researchers report. The ...

  1. 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.

  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. Medical hospitalizations in prostate cancer survivors.

    PubMed

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

    2016-07-01

    The objectives of the study were to explore the context and reasons for medical hospitalizations among prostate cancer survivors and to study their relationship with obesity and the type of prostate cancer treatment. A retrospective review of medical records was performed at an academic institution for male patients aged 40 years and older who were diagnosed and/or treated for prostate cancer 2 years prior to the study's observation period from January 2008 to December 2010. Unpaired t test, ANOVA, and Chi-square tests were used to compare patients' characteristics, admission types, and medical comorbidities by body mass index (BMI) and prostate cancer treatment. Mean age for the study population was 76 years (SD = 9.2). Two hundred and forty-five prostate cancer survivors were stratified into two groups: non-obese (BMI < 30 kg/m(2)) and obese (BMI ≥ 30 kg/m(2)). The study population's characteristics analyzed by BMI were similar including Gleason score, presence of metastatic disease and genitourinary-related side effects. Only 13 % of admissions were for complaints related to their genitourinary system. Neither the specific treatment that the patients had received for their prostate cancer, nor obesity was associated with the reasons for their medical admission. Survivorship after having a diagnosis of prostate cancer is often lengthy, and these men are at risk of being hospitalized, as they get older. From this inquiry, it has become clear that neither body mass index nor prior therapy is associated with specific admission characteristics, and only a minority of such admissions was directly related to prostate cancer or the genitourinary tract. PMID:27324503

  4. Immune Infiltration and Prostate Cancer

    PubMed Central

    Strasner, Amy; Karin, Michael

    2015-01-01

    It is becoming increasingly clear that inflammation influences prostate cancer (PCa) development and that immune cells are among the primary drivers of this effect. This information has launched numerous clinical trials testing immunotherapy drugs in PCa patients. The results of these studies are promising but have yet to generate a complete response. Importantly, the precise immune profile that determines clinical outcome remains unresolved. Individual immune cell types are divided into various functional subsets whose effects on tumor development may differ depending on their particular phenotype and functional status, which is often shaped by the tumor microenvironment. Thus, this review aims to examine the current knowledge regarding the role of inflammation and specific immune cell types in mediating PCa progression to assist in directing and optimizing immunotherapy targets, regimens, and responses and to uncover areas in which further research is needed. Finally, a summary of ongoing immunotherapy clinical trials in PCa is provided. PMID:26217583

  5. New agents for prostate cancer.

    PubMed

    Agarwal, N; Di Lorenzo, G; Sonpavde, G; Bellmunt, J

    2014-09-01

    The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has been revolutionized by the arrival of multiple novel agents in the past 2 years. Immunotherapy in the form of sipuleucel-T, androgen axis inhibitors, including abiraterone acetate and enzalutamide, a chemotherapeutic agent, cabazitaxel, and a radiopharmaceutical, radium-223, have all yielded incremental extensions of survival and have been recently approved. A number of other agents appear promising in early studies, suggesting that the armamentarium against castrate-resistant prostate cancer is likely to continue to expand. Emerging androgen pathway inhibitors include androgen synthesis inhibitors (TAK700), androgen receptor inhibitors (ARN-509, ODM-201), AR DNA binding domain inhibitors (EPI-001), selective AR downregulators or SARDs (AZD-3514), and agents that inhibit both androgen synthesis and receptor binding (TOK-001/galeterone). Promising immunotherapeutic agents include poxvirus vaccines and CTLA-4 inhibitor (ipilimumab). Biologic agents targeting the molecular drivers of disease are also being investigated as single agents, including cabozantinib (Met and VEGFR2 inhibitor) and tasquinimod (angiogenesis and immune modulatory agent). Despite the disappointing results seen from studies evaluating docetaxel in combination with other agents, including GVAX, anti-angiogentic agents (bevacizumab, aflibercept, lenalinomide), a SRC kinase inhibitor (dasatinib), endothelin receptor antagonists (atrasentan, zibotentan), and high-dose calcitriol (DN-101), the results from the trial evaluating docetaxel in combination with the clusterin antagonist, custirsen, are eagerly awaited. New therapeutic hurdles consist of discovering new targets, understanding resistance mechanisms, the optimal sequencing and combinations of available agents, as well as biomarkers predictive for benefit. Novel agents targeting bone metastases are being developed following the success of zoledronic acid

  6. [Optimization of prostate biopsy strategy in diagnosis of prostate cancer].

    PubMed

    Kimura, Go

    2016-01-01

    The prostate gland is the sole organ that uses not targeted but systematic biopsy in the pathological diagnosis of prostate cancer due to its anatomical location and lack of adequate imaging modality to depict cancer nodules clearly. The U.S. Preventive Services Task Force published that the harms of PSA based screening outweigh the benefits, yielding a grade D recommendation against screening. In this current situation, what we need is to optimize a biopsy template that maximizes the detection rate of clinically significant cancer and provides adequate pathological information for a treatment plan while minimizing the detection of indolent cancers and has good cost-effectiveness and safety. In this manuscript, optimal systematic biopsy templates and possible role of MRI-guided biopsy are reviewed. PMID:26793884

  7. 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

  8. Update: immunological strategies for prostate cancer.

    PubMed

    Drake, Charles G; Antonarakis, Emmanuel S

    2010-05-01

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

  9. 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.

  10. Shared gene expression alterations in prostate cancer and histologically benign prostate from patients with prostate cancer.

    PubMed

    Kosari, Farhad; Cheville, John C; Ida, Cristiane M; Karnes, R Jeffrey; Leontovich, Alexey A; Sebo, Thomas J; Erdogan, Sibel; Rodriguez, Erika; Murphy, Stephen J; Vasmatzis, George

    2012-07-01

    Prostate cancer (PCa) field effect alterations provide important clues regarding the initiation of these tumors and suggest targets for prevention or biomarkers for early detection. However, biomarkers of PCa field effects that have passed independent validation are lacking, largely because these alterations are subtle and difficult to distinguish from unrelated small changes in gene expression. We hypothesized that shared expression alterations in PCa and benign prostates containing PCa (BPCs) would have a higher potential for independent validation than alterations identified in BPCs alone. Expression analyses were performed on 37 PCas and 36 unmatched BPCs and were contrasted with 28 benign prostates (BPs) from patients free of PCa. Most of the protein-coding genes and nonexonic RNAs selected according to the hypothesis were validated by quantitative RT-PCR in an independent set of 51 BPCs and BPs. A statistical model based on two markers distinguished BPCs from BPs in the RT-PCR set and in an external microarray (area under the curve = 0.84 and 0.90, respectively). In addition, genes with predominant expression in stroma were identified by expression profiling of pure stroma and epithelial cells. Pathway analysis identified dysregulated platelet-derived growth factor receptor signaling in BPC stroma. These results validate our approach for finding PCa field effect alterations and demonstrate a PCa transcriptome fingerprint in nonneoplastic cells in prostates containing cancer. PMID:22640805

  11. FDG PET/CT in Peritoneal Metastasis From Prostate Cancer.

    PubMed

    Gungor, Serkan; Asa, Sertac; Kupik, Osman

    2016-09-01

    Prostate cancer is one of the leading causes of cancer death in men. The prognosis in prostate cancer is greatly worsened by the presence of metastases, which are most commonly found in bone, lung, liver, and brain. The peritoneum is an extremely uncommon metastatic site for prostate cancer, even in autopsy series. We present a case of FDG PET/CT demonstration of peritoneal metastasis from prostate cancer. PMID:27187732

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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. PMID:27325648

  19. Radiation Therapy for Prostate Cancer May Carry Certain Risks

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_157587.html Radiation Therapy for Prostate Cancer May Carry Certain Risks ... 3, 2016 THURSDAY, March 3, 2016 (HealthDay News) -- Radiation treatment for prostate cancer may put men at ...

  20. Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer?

    MedlinePlus

    ... html Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer? Study also suggests that cholesterol-lowering ... fatty beef and cheese was linked with more aggressive prostate cancer, the researchers found. A diet high ...

  1. Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer?

    MedlinePlus

    ... Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer? Study also suggests that cholesterol-lowering drugs may ... meats and cheese -- may affect how quickly their prostate cancer progresses, a new study suggests. "We show that ...

  2. Low Vitamin D Levels May Signal More Aggressive Prostate Cancer

    MedlinePlus

    ... html Low Vitamin D Levels May Signal More Aggressive Prostate Cancer But men should not expect supplements ... 2016 (HealthDay News) -- Prostate cancer may be more aggressive in men who are deficient in vitamin D, ...

  3. 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.

  4. Prostate cancer epigenetics and its clinical implications.

    PubMed

    Yegnasubramanian, Srinivasan

    2016-01-01

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

  5. 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

  6. 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.

  7. 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

  8. Antiepileptic drugs with histone deacetylase inhibition activity and prostate cancer risk: a population-based case-control study.

    PubMed

    Salminen, Jukka K; Tammela, Teuvo L J; Auvinen, Anssi; Murtola, Teemu J

    2016-05-01

    Previous studies suggest that antiepileptic drugs with histone deacetylase (HDAC) inhibitor properties may have prostate cancer preventive effects. We evaluated the association between antiepileptic drug use and prostate cancer risk in a population-based case-control study. The study included all new prostate cancer cases diagnosed in Finland in 1995-2002 and matched controls (24,657 case-control pairs) identified from the Finnish Cancer Registry and the Population Register Center, respectively. Information on antiepileptic drug purchases was obtained from the national prescription reimbursement database. Odds ratios and their 95 % confidence intervals were estimated using age-adjusted and multivariable-adjusted conditional logistic regression analysis. Compared to never-users of antiepileptic drugs, the overall prostate cancer risk was decreased among users of phenobarbital, carbamazepine, and valproic acid (multivariable-adjusted odds ratio (OR) 0.47, 95 % CI 0.24-0.92; OR 0.82, 95 % CI 0.71-0.94, and OR 0.62, 95 % CI 0.42-0.92, respectively), but not among users of other antiepileptic drugs. Overall prostate cancer risk decreased in a dose-dependent manner by cumulative amount, duration and yearly dosage (intensity) of HDAC inhibitors valproic acid and carbamazepine. The risk of advanced prostate cancer was decreased only among carbamazepine users (OR 0.65, 95 % CI 0.44-0.96). Our results support possible prostate cancer preventive effects of HDAC inhibitors. However, also phenobarbital use was associated with decreased prostate cancer risk, despite not having HDAC inhibiting activity. The mechanism of action for antiepileptic drugs in prostate cancer deserves further study. PMID:27038166

  9. Sotalol, but not digoxin is associated with decreased prostate cancer risk: A population-based case-control study.

    PubMed

    Kaapu, Kalle J; Ahti, Janne; Tammela, Teuvo L J; Auvinen, Anssi; Murtola, Teemu J

    2015-09-01

    Antiarrhythmic drug digoxin has been reported to have apoptosis-inducing and cytotoxic effects on prostate cancer cells. We evaluated the association between antiarrhythmic drug use and prostate cancer risk in a population-based case-control study. The study included all new prostate cancer cases diagnosed in Finland during 1995-2002 and matched controls (24,657 case-control pairs) obtained from the Finnish Cancer Registry and the Population Register Center, respectively. Information on antiarrhythmic drug purchases was obtained from national prescription database. Multivariable-adjusted conditional logistic regression model was used for data analysis. Compared to never-users of antiarrhythmic drugs, we found no significant association between digoxin use and prostate cancer risk overall [odds ratio (OR) 0.95, 95% confidence interval (CI): 0.89-1.01] or for advanced prostate cancer risk (OR: 0.90, 95% CI: 0.77-1.05). The result was similar also for other antiarrhythmic drugs, with the exception of sotalol, users of which had decreased risk of advanced prostate cancer (OR: 0.73, 95% CI: 0.56-0.96). Also the overall prostate cancer risk decreased by duration of sotalol use (p for trend 0.038). We show that digoxin or other common antiarrhythmic drugs generally do not associate with prostate cancer risk at population level during maximum follow-up of eight years. However, we cannot rule out longer term protective effects of digoxin. K(+) -channel blocker sotalol shows some promise as prostate cancer preventing agent. However, findings need to be confirmed in further studies. PMID:25656312

  10. Development of PROSTVAC immunotherapy in prostate cancer.

    PubMed

    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

  11. 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

  12. [Sharing uncertainties of prostate cancer screening].

    PubMed

    Selby, Kevin; Auer, Reto; Valerio, Massimo; Jichlinski, Patrice; Cornuz, Jacques

    2015-11-25

    The decision of whether our patients should undergo prostate cancer screening with the prostate specifc antigen (PSA) test remains daunting. The role of the primary care doctor is to help men decide between a potential decrease in mortality from a slow evolving but sometimes lethal cancer, and the risk of diagnosing and treating cancers that would have otherwise been indolent and asymptomatic. We can structure our discussions with three steps: choice, option, and decision making. A decision aid, such as the one that we have adapted and simplifed from the Collège des médecins du Québec, can help with this complex decision. PMID:26742351

  13. SPARCL1 suppresses metastasis in prostate cancer

    PubMed Central

    Xiang, Yuzhu; Qiu, Qingchao; Jiang, Ming; Jin, Renjie; Lehmann, Brian D; Strand, Douglas W; Jovanovic, Bojana; DeGraff, David J; Zheng, Yi; Yousif, Dina A; Case, Thomas C; Yi, Jia; Cates, Justin M; Virostko, John; He, Xiusheng; Jin, Xunbo; Hayward, Simon W; Matusik, Robert J; George, Alfred L; Yi, Yajun

    2013-01-01

    Purpose Metastasis, the main cause of death from cancer, remains poorly understood at the molecular level. Experimental design Based on a pattern of reduced expression in human prostate cancer tissues and tumor cell lines, a candidate suppressor gene (SPARCL1) was identified. We used in vitro approaches to determine whether overexpression of SPARCL1 affects cell growth, migration, and invasiveness. We then employed xenograft mouse models to analyze the impact of SPARCL1 on prostate cancer cell growth and metastasis in vivo. Results SPARCL1 expression did not inhibit tumor cell proliferation in vitro. By contrast, SPARCL1 did suppress tumor cell migration and invasiveness in vitro and tumor metastatic growth in vivo, conferring improved survival in xenograft mouse models. Conclusions We present the first in vivo data suggesting that SPARCL1 suppresses metastasis of prostate cancer. PMID:23916135

  14. The evolving biology and treatment of prostate cancer

    PubMed Central

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

    2007-01-01

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

  15. Measurement of quality of life in men with prostate cancer.

    PubMed

    Albaugh, Jeffrey; Hacker, Eileen Danaher

    2008-02-01

    Prostate cancer continues to be one of the most common cancers diagnosed in men. In light of the excellent survival rates for prostate cancer, quality of life is a primary concern during and following prostate cancer treatment. Quality of life is defined and determined in multiple ways. This article explores quality of life in men with prostate cancer. Quality-of-life dimensions, measurement tools, and implications of quality of life with prostate cancer on clinical practice for oncology nurses will be presented. PMID:18258577

  16. 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 ...

  17. 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

  18. 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

  19. 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

  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. Current clinical challenges in prostate cancer

    PubMed Central

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

    2013-01-01

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

  2. Cytoskeleton targeting value in prostate cancer treatment

    PubMed Central

    Martin, Sarah K; Kamelgarn, Marisa; Kyprianou, Natasha

    2014-01-01

    Prostate cancer is a disease that affects hundreds of thousands of men in the United States each year. In the early stages of advanced prostate cancer, the disease can be suppressed by androgen deprivation therapy (ADT). Eventually, however, most patients experience resistance to androgen deprivation, and their treatment transitions to alternative targeting of the androgen axis with abiraterone and enzalutamide, as well as taxane-based chemotherapy. Development of advanced castration-resistant prostate cancer (CRPC) is a consequence of lack of an apoptotic response by the tumor cells to treatment. Understanding the mechanisms contributing to prostate tumor therapeutic resistance and progression to metastasis requires dissection of the signaling mechanisms navigating tumor invasion and metastasis as mediated by cell-matrix interactions engaging components of the extracellular matrix (ECM), to form adhesion complexes. For a tumor call to metastasize from the primary tumor, it requires disruption of cell-cell interactions from the surrounding cells, as well as detachment from the ECM and resistance to anoikis (apoptosis upon cell detachment from ECM). Attachment, movement and invasion of cancer cells are functionally facilitated by the actin cytoskeleton and tubulin as the structural component of microtubules. Transforming growth factor (TGF)-β has tumor-inhibitory activity in the early stages of tumorigenesis, but it promotes tumor invasive characteristics in metastatic disease. Recent evidence implicates active (dephosphorylated) cofilin, an F-actin severing protein required for cytoskeleton reorganization, as an important contributor to switching TGF-β characteristics from a growth suppressor to a promoter of prostate cancer invasion and metastasis. Cancer cells eventually lose the ability to adhere to adjacent neighboring cells as well as ECM proteins, and via epithelial-mesenchymal transition (EMT), acquire invasive and metastatic characteristics. Microtubule

  3. Dietary acrylamide and risk of prostate cancer.

    PubMed

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

    2012-07-15

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

  4. 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. PMID:27453073

  5. 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

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

    PubMed

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

    2016-03-01

    Prostate cancer is the most common cancer in men. Modern medical imaging is intimately involved in the diagnosis and management of prostate cancer. Ultrasound is primarily used to guide prostate biopsy to establish the diagnosis of prostate carcinoma. Prostate magnetic resonance imaging uses a multiparametric approach, including anatomic and functional imaging sequences. Multiparametric magnetic resonance imaging can be used for detection and localization of prostate cancer and to evaluate for disease recurrence. Computed tomography and scintigraphic imaging are primarily used to detect regional lymph node spread and distant metastases. Recent advancements in ultrasound, multiparametric magnetic resonance imaging, and scintigraphic imaging have the potential to change the way prostate cancer is diagnosed and managed. This article addresses the major imaging modalities involved in the evaluation of prostate cancer and updates the reader on the state of the art for each modality. PMID:26087969

  7. Role of PARP-1 in prostate cancer

    PubMed Central

    Deshmukh, Dhanraj; Qiu, Yun

    2015-01-01

    Poly (ADP-ribose) polymerase-1 (PARP-1) is an enzyme that catalyzes the covalent attachment of polymers of ADP-ribose (PAR) moieties on itself and its target proteins. PARP1 activity is frequently deregulated in various cancers and therefore it has emerged as a new drug target for cancer therapy. The role of PARP-1 in DNA repair has been well documented and BRCA mutations are implicated for determining the sensitivity to PARP inhibitors. Recent studies also point to a role of PARP-1 in transcription regulation which may contribute to oncogenic signaling and cancer progression. Given that efficacy of PARP inhibitors are also seen in patients not harboring BRCA mutations, some other mechanisms might also be involved. In the present review, we highlight the mechanisms by which PARP-1 regulates gene expression in prostate cancer and provide an overview of the ongoing clinical trials using PARP inhibitors in various cancers including prostate cancer. PMID:26069882

  8. Stereotactic body radiotherapy for prostate cancer.

    PubMed

    Henderson, D R; Tree, A C; van As, N J

    2015-05-01

    The use of stereotactic body radiotherapy (SBRT) for localised prostate cancer is now supported by a substantial body of non-randomised data, with medium-term outcomes consistent with current standard radiotherapy. The ability to deliver profoundly hypofractionated treatment, combined with the relatively low α/β ratio of prostate cancer, may result in a more favourable therapeutic ratio, presenting an opportunity for isotoxic dose escalation. Furthermore, as treatment can be given in five attendances, SBRT has the potential both to reduce costs and improve patient quality of life. However, in a treatment landscape with many competing options of broadly similar efficacy, randomised trials are essential to define the relative benefits of this approach. SBRT also has an emerging application in oligometastatic prostate cancer, with promising early outcomes for delaying disease progression and deferring the need for androgen deprivation therapy. PMID:25707911

  9. CYP17 inhibitors for prostate cancer therapy.

    PubMed

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

    2011-05-01

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

  10. CYP17 inhibitors for prostate cancer therapy

    PubMed Central

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

    2010-01-01

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

  11. [THE EVOLUTION OF MARKERS OF PROSTATE CANCER].

    PubMed

    Peshkov, M N; Generozov, E V; Kostryukova, E S

    2016-03-01

    The implementation of biochemical laboratory tests in oncology practice increased exponentially during last decades and continues to be in progress nowadays. The application of modern molecular genetic technologies permits using diagnostic systems with greater diagnostic sensitivity and specificity. The new tests are actively implemented permitting to diagnose physical presence of tumor systemic manifestations of malignant neoplasm (cachexia, pyrexia), paraneoplastic syndromes and also to detect tumor markers. The oncomarker permits to differentiate malignant from benign tumor on the basis of quantitative differences in content of corresponding antigene-tumor marker in blood serum independently of localization of tumor nidus. The prostate cancer is a medical social problem of male population. On initial stages, this disease can take its course asymptomatically or with symptomatic conditioned by such concomitant and more prevalent pathologies as chronic prostatitis and prostate benign hyperplasia. The early diagnostic ofprostate cancer permits implementing timely radical treatment frequently contributing to total recovery of patients. The article presents detailed description of evolutionary conception of markers using in diagnostic, staging and prognostication of course of prostate cancer. The acid phosphatase was applied for the first time in early diagnostic of staging of prostate cancer in 1974. Nowadays, in century of "OMX"-technologies, in common clinical practice detection of RNA in urine of patient is used for staging diagnostic and prognostication of progression of process of tissue neotransformation. PMID:27506103

  12. Translational Molecular Imaging of Prostate Cancer

    PubMed Central

    Kiess, Ana P.; Cho, Steve Y.; Pomper, Martin G.

    2013-01-01

    Prostate cancer is a heterogeneous disease, and its management is now evolving to become more personalized and to incorporate new targeted therapies. With these new changes comes a demand for molecular imaging techniques that can not only detect disease but also assess biology and treatment response. This review article summarizes current molecular imaging approaches in prostate cancer (e.g. 99mTc bone scintigraphy and 18F-fluorodeoxyglucose positron emission tomography) and highlights emerging clinical and preclinical imaging agents, with an emphasis on mechanism and clinical application. Emerging agents at various stages of clinical translation include radiolabeled analogs of lipid, amino acid, and nucleoside metabolism, as well as agents more specifically targeting prostate cancer biomarkers including androgen receptor, prostate-specific membrane antigen and others. We also highlight new techniques and targeted contrast agents for magnetic resonance imaging and spectroscopy. For all these imaging techniques, a growing and important unmet need is for well-designed prospective clinical trials to establish clear indications with clinical benefit in prostate cancer. PMID:24159427

  13. Applications of transrectal ultrasound in prostate cancer

    PubMed Central

    Harvey, C J; Pilcher, J; Richenberg, J; Patel, U; Frauscher, F

    2012-01-01

    Transrectal ultrasound (TRUS) was first developed in the 1970s. TRUS-guided biopsy, under local anaesthetic and prophylactic antibiotics, is now the most widely accepted method to diagnose prostate cancer. However, the sensitivity and specificity of greyscale TRUS in the detection of prostate cancer is low. Prostate cancer most commonly appears as a hypoechoic focal lesion in the peripheral zone on TRUS but the appearances are variable with considerable overlap with benign lesions. Because of the low accuracy of greyscale TRUS, TRUS-guided biopsies have become established in the acquisition of systematic biopsies from standard locations. The number of systematic biopsies has increased over the years, with 10–12 cores currently accepted as the minimum standard. This article describes the technique of TRUS and biopsy and its complications. Novel modalities including contrast-enhanced modes and elastography as well as fusion techniques for increasing the sensitivity of TRUS-guided prostate-targeted biopsies are discussed along with their role in the diagnosis and management of prostate cancer. PMID:22844031

  14. Stroma–epithelium crosstalk in prostate cancer

    PubMed Central

    Niu, Yi-Nong; Xia, Shu-Jie

    2009-01-01

    The critical role played by stroma–epithelium crosstalk in carcinogenesis and progression of prostate cancer has been increasingly recognized. These interactions are mediated by a variety of paracrine factors secreted by cancer cells and/or stromal cells. In human prostate cancer, reactive stroma is characterized by an increase in myofibroblasts and a corresponding amplification of extracellular matrix production and angiogenesis. Permanent genetic mutations have been reported in stromal cells as well as in tumour cells. Transforming growth factor-β, vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor signalling pathways are involved in the process of angiogenesis, whereas hepatocyte growth factor, insulin-like growth factor-1, epidermal growth factor, CXC12 and Interleukin-6 play active roles in the progression, androgen-independent conversion and distal metastasis of prostate cancer. Some soluble factors have reciprocal interactions with androgens and the androgen receptor (AR), and can even activate AR in the absence of the androgen ligand. In this article, we review the complex interactions between cancer cells and the surrounding microenvironment, and discuss the potential therapeutic targets in the stromal compartment of prostate cancer. PMID:19098934

  15. Changing trends of prostate cancer in Asia.

    PubMed

    Pu, Y S; Chiang, H S; Lin, C C; Huang, C Y; Huang, K H; Chen, J

    2004-06-01

    Although Asian people have the lowest incidence and mortality rates of prostate cancer in the world, these rates have risen rapidly in the past two decades in most Asian countries. Prostate cancer has become one of the leading male cancers in some Asian countries. In 2000, the age-adjusted incidence was over 10 per 100000 men in Japan, Taiwan, Singapore, Malaysia, the Philippines and Israel. Although some of the increases may result from enhanced detection, much of the increased incidence may be associated with westernization of the lifestyle, with increasing obesity and increased consumption of fat. The differences in incidences between native Americans and Asian immigrants are getting smaller, reflecting a possible improvement of diagnostic efforts and changes of environmental risk factors in Asian immigrants. Nevertheless, the huge variations in incidences among ethnic groups imply that there are important genetic risk factors. The stage distributions of prostate cancer in Asian populations are still unfavorable compared to those of Western developed countries. However, a trend towards diagnosing cancer with more favorable prognosis is seen in most Asian countries. Both genetic and environmental risk factors responsible for elevated risks in Asian people are being identified, which may help to reduce prostate cancer incidence in a chemopreventive setting. PMID:15672937

  16. 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

  17. [Prostate-rectum spacers: optimization of prostate cancer irradiation].

    PubMed

    Zilli, T; Benz, E; Miralbell, R

    2014-06-01

    In the curative radiotherapy of localized prostate cancer, improvements in biochemical control observed with dose escalation have been counterbalanced by an increase in radiation-induced toxicity. The injection of biodegradable spacers between prostate and rectum represents a new frontier in the optimization of radiotherapy treatments for patients with localized disease. Transperineal injection of different types of spacers under transrectal ultrasound guidance allows creating a 7-to-20 mm additional space between the prostate and the anterior rectal wall lasting 3 to 12 months. Dosimetrically, a relative reduction in the rectal volume receiving at least 70 Gy (V70) in the order of 43% to 84% is observed with all types of spacers, regardless of the radiotherapy technique used. Preliminary clinical results show for all spacers a good tolerance and a possible reduction in the acute side effects rate. The aim of the present systematic review of the literature is to report on indications as well as dosimetric and clinical advantages of the different types of prostate-rectum spacers commercially available (hydrogel, hyaluronic acid, collagen, biodegradable balloon). PMID:24746454

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

    PubMed Central

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

    2010-01-01

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

  19. MMP inhibition in prostate cancer.

    PubMed

    Lokeshwar, B L

    1999-06-30

    Matrix metalloproteinases (MMPs) play a significant role during the development and metastasis of prostate cancer (CaP). CaP cells secrete high levels of MMPs and low levels of endogenous MMP inhibitors (TIMPs), thus creating an excess balance of MMPs. Established CaP cell lines that express high levels of MMPs frequently metastasize to the bone and the lungs. Drugs such as Taxol and alendronate that reduce cell motility and calcium metabolism reduce bony metastasis of xenografted CaP tumors. We tested several synthetic, nontoxic inhibitors of MMPs that can be administered orally, including doxycycline (DC) and chemically modified tetracyclines (CMTs) on CaP cells in vitro and on a rat CaP model in vivo. Among several anti-MMP agents tested, CMT-3 (6-deoxy, 6-demethyl,4-de-dimethylamino tetracycline) showed highest activity against CaP cell invasion and cell proliferation. Micromolar concentration of CMT-3 and DC inhibited both the secretion and activity of MMPs by CaP cells. When tested for in vivo efficacy in the Dunning rat CaP model by daily oral gavage, CMT-3 and DC both reduced the lung metastases (> 50%). CMT-3, but not DC, inhibited tumor incidence (55 +/- 9%) and also reduced the tumor growth rate (27 +/- 9.3%). More significantly, the drugs showed minimum systemic toxicity. Ongoing studies indicate that CMT-3 may inhibit the skeletal metastases of CaP cells and delay the onset of paraplegia due to lumbar metastases. These preclinical studies provide the basis for clinical trials of CMT-3 for the treatment of metastatic disease. PMID:10415736

  20. Reduction in the risk of prostate cancer: future directions after the Prostate Cancer Prevention Trial.

    PubMed

    Crawford, E David; Andriole, Gerald L; Marberger, Michael; Rittmaster, Roger S

    2010-03-01

    The landmark Prostate Cancer Prevention Trial (PCPT) generated interest in the potential health benefits and cost of reducing prostate cancer risk--specifically, the potential role of 5alpha-reductase inhibitors. However, the PCPT raised several unanswered questions, including the cause and significance of the increased incidence of high-grade tumors associated with finasteride. In the present study, we review the PCPT findings and unanswered questions, next steps in this field, and ongoing prostate cancer prevention trials addressing these unanswered questions. Particular emphasis is placed on the design of the second large-scale trial of a 5alpha-reductase inhibitor, the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial. PMID:20035983

  1. The Genomic Landscape of Prostate Cancer

    PubMed Central

    Spans, Lien; Clinckemalie, Liesbeth; Helsen, Christine; Vanderschueren, Dirk; Boonen, Steven; Lerut, Evelyne; Joniau, Steven; Claessens, Frank

    2013-01-01

    By the age of 80, approximately 80% of men will manifest some cancerous cells within their prostate, indicating that prostate cancer constitutes a major health burden. While this disease is clinically insignificant in most men, it can become lethal in others. The most challenging task for clinicians is developing a patient-tailored treatment in the knowledge that this disease is highly heterogeneous and that relatively little adequate prognostic tools are available to distinguish aggressive from indolent disease. Next-generation sequencing allows a description of the cancer at an unprecedented level of detail and at different levels, going from whole genome or exome sequencing to transcriptome analysis and methylation-specific immunoprecipitation, followed by sequencing. Integration of all these data is leading to a better understanding of the initiation, progression and metastatic processes of prostate cancer. Ultimately, these insights will result in a better and more personalized treatment of patients suffering from prostate cancer. The present review summarizes current knowledge on copy number changes, gene fusions, single nucleotide mutations and polymorphisms, methylation, microRNAs and long non-coding RNAs obtained from high-throughput studies. PMID:23708091

  2. [Prostate cancer external beam radiotherapy].

    PubMed

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

    2016-09-01

    The prostate external beam radiotherapy techniques are described, when irradiating the prostate or after prostatectomy, with and without pelvic lymph nodes. The following parts are presented: indications of radiotherapy, total dose and fractionation, planning CT image acquisition, volume of interest delineation (target volumes and organs at risk) and margins, Intensity modulated radiotherapy planning and corresponding dose-volume constraints, and finally Image guided radiotherapy. PMID:27516051

  3. PSA Screening Has Led to Overtreatment of Many Prostate Cancers

    Cancer.gov

    Screening for prostate cancer with the prostate-specific antigen (PSA) test has led to overtreatment of many prostate cancers, including aggressive treatments in older men considered to be at low risk for progression of the disease according to a study published in the July 26, 2010 Archives of Internal Medicine.

  4. Stromal androgen receptor roles in the development of normal prostate, benign prostate hyperplasia, and prostate cancer.

    PubMed

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

    2015-02-01

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

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

    PubMed Central

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

    2016-01-01

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

  6. [Recent advances in diagnosis of prostate cancer].

    PubMed

    Hara, Isao

    2016-01-01

    Most valuable tool for diagnosis of prostate cancer is PSA. Although PSA is highly specific for organ, it is not so specific for disease. Therefore, about 70% of patients whose PSA value is 4-10 ng/mL are forced to undergo unnecessary prostate biopsy. In order to discriminate the unnecessary biopsies, several markers such as free/total PSA ratio, PSA density, and PSA velocity have been developed. However, none of these markers were widely approved in daily clinical settings. Prostate cancer antigen 3 (PCA3) is thought to be a useful marker for necessity of repeat biopsy. Functional MR imaging such as dynamic contrast enhancement (DCE), diffusion weighted imaging(DWI), MR spectroscopy (MRS) have been developed. Recently MRI-TRUS fusion biopsy is gathering attention. In terms of pathology, atypical glands but not high grade PIN require repeat biopsy after 3 to 6 months from initial biopsy. PMID:26793874

  7. What's wrong with chemoprevention of prostate cancer?

    PubMed

    Justman, Stewart

    2011-12-01

    When prostate-specific antigen (PSA) testing was introduced, proponents expected it to cut prostate-cancer mortality and did not expect it to unleash an epidemic of unnecessary treatments. Now that evidence of a mortality benefit remains unclear while evidence of overtreatment in undeniable, there is understandable interest in reducing the human costs of the PSA system. Two related drugs, finasteride and dutasteride, both proven to reduce the incidence of prostate cancer and the "risk of diagnosis," are being promoted accordingly. However, if not for the flaws of the PSA system the use of these drugs for purposes of prevention would lose its rationale. Not only are the drugs in this sense dependent on a faulty system, but their own mortality benefits are as speculative as PSA's-in addition to which, they introduce new risks. PMID:22146025

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

    PubMed Central

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

    2016-01-01

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

  9. The Prostate

    MedlinePlus

    ... Renal Cell) Cancer Leukemia Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ... Publications Reports What You Need To Know About™ Prostate Cancer This booklet is about prostate cancer. Learning about ...

  10. 4-Kallikrein Test and Kallikrein Markers in Prostate Cancer Screening.

    PubMed

    McDonald, Michelle L; Parsons, J Kellogg

    2016-02-01

    A preponderance of clinical evidence supports a significant public health benefit for prostate-specific antigen (PSA)-based screening and early detection of prostate cancer in appropriately counseled and selected men. Population-based screening with PSA decreases prostate cancer mortality; however, because of relatively poor specificity, PSA-based screening may also increase the detection of clinically insignificant cancers that would otherwise never require treatment. Use of newer biomarkers that increase the specificity for prostate cancer detection may aid in risk stratification and the appropriate identification of men for prostate biopsy. The authors review the 4-kallikrein panel and 4K probability score. PMID:26614027

  11. Hypofractionated Radiotherapy for Favorable Risk Prostate Cancer

    SciTech Connect

    Rene, Nicholas; Faria, Sergio; Cury, Fabio; David, Marc; Duclos, Marie; Shenouda, George; Souhami, Luis

    2010-07-01

    Purpose: Since the recognition that prostate cancer probably has a low {alpha}/{beta} ratio, hypofractionated radiotherapy has become an attractive treatment option for localized prostate cancer. However, there is little experience with the use of hypofractionation delivering a high biologically equivalent dose. We report our experience with high-dose hypofractionated radiotherapy. Material and Methods: A total of 129 patients with favorable risk prostate cancer were treated with three-dimensional conformal radiotherapy treatment plans to the dose of 66 Gy in 22 fractions, prescribed at the isocenter. Planning target volume consisted of the prostate plus a uniform 7-mm margin, including the rectal margin. No patient received hormonal therapy. Toxicity was prospectively graded by the Common Toxicity Criteria version3. Biochemical relapse was defined as postradiotherapy nadir prostate-specific antigen + 2 ng/mL. Results: With a median follow-up of 51 months, the 5-year actuarial biochemical control rate is 98%. The only 3 cases with biochemical failure did not have a clinical local relapse. More than 50% of patients did not develop acute toxicity. For late toxicity, the worst crude rate of Grade {>=}2 genitourinary (GU) and gastrointestinal (GI) toxicity seen at any time during follow-up were 32% and 25%, respectively. There was no Grade 4 or 5 toxicity. At the last follow-up, persistent Grade {>=}2 late GU and GI toxicity were 2% and 1.5%, respectively. Conclusions: This hypofractionated regimen provides excellent biochemical control in favorable risk prostate cancer with an acceptable rate of late toxicity. Further studies exploring this hypofractionation regimen are warranted.

  12. Magnetic resonance imaging for prostate cancer radiotherapy.

    PubMed

    Dinh, Cuong V; Steenbergen, Peter; Ghobadi, Ghazaleh; Heijmink, Stijn W T J P; Pos, Floris J; Haustermans, Karin; van der Heide, Uulke A

    2016-03-01

    For radiotherapy of prostate cancer, MRI is used increasingly for delineation of the prostate gland. For focal treatment of low-risk prostate cancer or focal dose escalation for intermediate and high-risk cancer, delineation of the tumor is also required. While multi-parametric MRI is well established for detection of tumors and for staging of the disease, delineation of the tumor inside the prostate is not common practice. Guidelines, such as the PI-RADS classification, exist for tumor detection and staging, but no such guidelines are available for tumor delineation. Indeed, interobserver studies show substantial variation in tumor contours. Computer-aided tumor detection and delineation may help improve the robustness of the interpretation of multi-parametric MRI data. Comparing the performance of an earlier developed model for tumor segmentation with expert delineations, we found a significant correlation between tumor probability in a voxel and the number of experts identifying this voxel as tumor. This suggests that the model agrees with 'the wisdom of the crowd', and thus could serve as a reference for individual physicians in their decision making. With multi-parametric MRI it becomes feasible to revisit the GTV-CTV concept in radiotherapy of prostate cancer. While detection of index lesions is quite reliable, contouring variability and the low sensitivity to small lesions suggest that the remainder of the prostate should be treated as CTV. Clinical trials that investigate the options for dose differentiation, for example with dose escalation to the visible tumor or dose reduction to the CTV, are therefore warranted. PMID:26858164

  13. Expression and Localization of Aquaporins in Benign Prostate Hyperplasia and Prostate Cancer

    PubMed Central

    Hwang, Insang; Hwang, Eu-Chang; Song, Seung Hee; Lee, Hyun-Suk; Kim, Sun-Ouck; Kang, Taek-Won; Kwon, Dongdeuk; Park, Kwangsung

    2012-01-01

    The aquaporin (AQP) families of water channels are intrinsic membrane proteins that facilitate selective water and small solute movement across the plasma membrane. The purposes of this study were to determine the expression and localization of AQPs in benign prostatic hyperplasia and prostate cancer. Prostatic tissue was collected from patients with benign prostatic hyperplasia or prostate cancer by transurethral resection of the prostate. The expression and cellular localization of the AQPs were determined in the human prostate by Western blot and immunohistochemistry. AQP1, 3, and 9 were expressed in the human prostate. Western blot analysis revealed bands at 28-36 kDa for the AQP1, 3, and 9 proteins. Of these proteins, AQP3 and 9 were expressed in the epithelium. Immunolabeling showed that AQP1 was mainly expressed in the capillaries and venules of the prostate, AQP9 was expressed in the cytoplasm of the epithelium, and AQP3 was mainly associated with the plasma membrane of the prostatic epithelium. Only AQP3 expression was localized in the cell membrane, and expressed AQP3 was translocated to the cytoplasm in prostate cancer. The epithelium in the human prostate expresses AQP3 and 9 proteins, and the capillaries and venules of the prostate express AQP1. Characterizing or modifying the expression of AQP3 may lead to an understanding of the role of the AQPs in human prostatic disease. PMID:23323224

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

    PubMed Central

    2014-01-01

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

  15. PSA Velocity Does Not Improve Prostate Cancer Detection

    Cancer.gov

    A rapid increase in prostate-specific antigen (PSA) levels is not grounds for automatically recommending a prostate biopsy, according to a study published online February 24, 2011, in the Journal of the National Cancer Institute.

  16. Metastatic Sites Predict Prostate Cancer Survival.

    PubMed

    2016-05-01

    A new meta-analysis of clinical trial data from patients with metastatic castration-resistant prostate cancer indicates that overall survival is strongly influenced by where the disease spreads. Men with visceral disease-liver or lung metastases-fare worse than those with bone or lymph node involvement. PMID:27001152

  17. [Primary prevention of urologic tumors: prostate cancer].

    PubMed

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

    2011-10-01

    Assessment of the role of vitamins and micronutrients in the primary prevention of prostate cancer has changed dramatically in the past 10 years. Efforts to confirm the efficacy of a single substance have not yet succeeded. Therefore, such recommendations should at present no longer be given. Consideration could even be given to discussing whether additional large-scale interventional studies are expedient in this regard. There is still solid evidence that a well-balanced moderate diet, reduced consumption of milk products, and an Asian or Mediterranean diet are not only beneficial for general good health but can also prevent the development of prostate cancer. This should be the focus of further epidemiological studies. Thus, one can certainly speak of a paradigm shift in the prevention of prostate cancer. In contrast, available data on chemoprevention with 5α-reductase inhibitors is unequivocal: intake of finasteride as well as dutasteride correlates with significantly decreased evidence for prostate cancer. Converting this result into urologic practice remains the topic of extensive controversy. PMID:21927877

  18. The Molecular Taxonomy of Primary Prostate Cancer.

    PubMed

    2015-11-01

    There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects. PMID:26544944

  19. New genetic variants associated with prostate cancer

    Cancer.gov

    Researchers have newly identified 23 common genetic variants -- one-letter changes in DNA known as single-nucleotide polymorphisms or SNPs -- that are associated with risk of prostate cancer. These results come from an analysis of more than 10 million SNP

  20. Altered Endosome Biogenesis in Prostate Cancer has Biomarker Potential

    PubMed Central

    Johnson, Ian R D; Parkinson-Lawrence, Emma J; Shandala, Tetyana; Weigert, Roberto; Butler, Lisa M; Brooks, Doug A

    2016-01-01

    Prostate cancer is the second most common form of cancer in males, affecting one in eight men by the time they reach the age of 70. Current diagnostic tests for prostate cancer have significant problems with both false negatives and false positives, necessitating the search for new molecular markers. A recent investigation of endosomal and lysosomal proteins revealed that the critical process of endosomal biogenesis might be altered in prostate cancer. Here, a panel of endosomal markers was evaluated in prostate cancer and non-malignant cells and a significant increase in gene and protein expression was found for early, but not late endosomal proteins. There was also a differential distribution of early endosomes, and altered endosomal traffic and signalling of the transferrin receptors (TFRC and TFR2) in prostate cancer cells. These findings support the concept that endosome biogenesis and function is altered in prostate cancer. Microarray analysis of a clinical cohort confirmed the altered endosomal gene expression observed in cultured prostate cancer cells. Furthermore, in prostate cancer patient tissue specimens, the early endosomal marker and adaptor protein APPL1 showed consistently altered basement membrane histology in the vicinity of tumours and concentrated staining within tumour masses. These novel observations on altered early endosome biogenesis provide a new avenue for prostate cancer biomarker investigation and suggest new methods for the early diagnosis and accurate prognosis of prostate cancer. PMID:25080433

  1. Olaparib Targets Some Advanced Prostate Cancers.

    PubMed

    2016-01-01

    In the phase II TOPARP-A clinical trial, patients with metastatic castrate-resistant prostate cancer who were treated with the PARP inhibitor olaparib lived nearly three times longer without their cancer worsening if their tumors had mutations in at least one of 12 DNA repair genes. However, physicians say that a larger trial is needed to confirm olaparib's effectiveness against the disease before they start routinely sequencing tumors and prescribing the drug. PMID:26658963

  2. [Epidemiological situation of prostate cancer in Spain].

    PubMed

    Granado de la Orden, S; Saá Requejo, C; Quintás Viqueira, A

    2006-06-01

    Prostate cancer is the third most frequent neoplasms in Spanish men and the third cause of cancer death. Incidence grows up with the increase of age. 90% of cases are diagnostic in people over 65 years old. Etiology is quite unknown and has been associated with environmental exposure, life style, family sign and genetic factors. In 2002 mortality rate was 21.5/ 100.000 (situated among the lowest in Europe), with more than 5.000 deaths. Trend of mortality has grown up until 1998, from this year it has decreased due to improve on diagnostic and treatment. In order to study prostate cancer incidence we find a difficulty due to shortage of population cancer register. Estimations have found incidence rates of 45.33/100.000 which are among the lowest in Europe. Annual incidence of prostatic cancer has grown up in all Spanish registers, not only improve in register systems explains it, but also the development of diagnosis tests with a higher survival from the beginning of 90s (86% the first year after diagnosis and 65,5% five years after diagnosis), similar to other European countries. Blow up the cancer register system is necessary to know the incidence and prevalence, to assess survival and effectiveness of screening programs and to improve the knowledge of risk factors. PMID:16921834

  3. Tumor microenvironment and metabolism in prostate cancer.

    PubMed

    Chiarugi, Paola; Paoli, Paolo; Cirri, Paolo

    2014-04-01

    Prostate cancer is no longer viewed mostly as a disease of abnormally proliferating epithelial cells, but rather as a disease affecting the complex interactions between the cells of the prostate epithelial compartment and the surrounding stromal compartment in which they live. Indeed, the microenvironment in which tumor cells evolve towards an aggressive phenotype is highly heterogeneous, as it is composed of different cell populations such as endothelial cells, fibroblasts, macrophages, and lymphocytes, either resident or trans-differentiated by bone marrow-derived mesenchymal stem cells recruited at the tumor site. Cancer-associated fibroblasts, the most abundant population within this microenvironment, exert a mandatory role in prostate cancer progression as they metabolically sustain cancer cell survival and growth, recruit inflammatory and immune cells, and promote cancer cells stemness and epithelial mesenchymal transition, thereby favoring metastatic dissemination of aggressive cancers. The interruption of this two-compartment crosstalk, together with the idea that stromal cells are mostly vulnerable, being drug-sensitive, could lead to the development of anticancer therapies that target tumor stromal elements. PMID:24787298

  4. The essential role of methylthioadenosine phosphorylase in prostate cancer

    PubMed Central

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

    2016-01-01

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

  5. Defining young in the context of prostate cancer.

    PubMed

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

    2015-03-01

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

  6. Defining Young in the Context of Prostate Cancer

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Chang, R T M; Kirby, Roger; Challacombe, B J

    2012-04-01

    BPH is one of the most common diseases of older men, with more than 70% of men over 70 years affected, and prostate cancer is the most common cancer in men in the UK. Prostate cancer generally presents in one of three ways: asymptomatic patients who are screened (usually by a PSA test); men with LUTS who are investigated and undergo prostate biopsy; or patients with symptoms of metastasis such as bone pain. Men can be reassured that the main cause of LUTS is BPH. Only a small proportion of men have LUTS that are directly attributable to prostate cancer. Digital rectal examination (DRE) gives an evaluation of prostate size, which is relevant in particular to BPH management, and along with PSA testing it is one of the only ways of differentiating clinically between BPH and prostate cancer. If a nodular abnormality is present there is around a 50% chance of a diagnosis of prostate cancer being made on biopsy. Raised levels of serum PSA may be suggestive of prostate cancer, but diagnosis requires histological confirmation in almost every case. A normal PSA, PSA density and DRE can give reasonable confidence with regards to excluding clinically significant prostate cancer. BPH is not a known risk factor for prostate cancer, although the two frequently coexist. Age is the strongest predictor of prostate cancer risk, along with family history. BPH is not considered to be a precursor of prostate cancer. It is likely that although BPH may not make prostate cancer more likely to occur, it may increase the chance of diagnosing an incidental cancer. PMID:22792684

  8. New Developments in the Medical Management of Prostate Cancer

    PubMed Central

    Kohli, Manish; Tindall, Donald J.

    2010-01-01

    Prostate cancer is a substantial public health burden and a leading cause of cancer—related morbidity and mortality in the United States despite the observation that annual prostate cancer—specific mortality rates have been declining during the previous decade. Although the reasons for this positive development are unclear, a combination of factors may have contributed. This update will review ongoing developments and summarize therapeutic advances in prostate cancer treatment on the basis of the current understanding of prostate cancer biology. Literature for this review was selected in 2009 by searching PubMed for the following keywords: prostatic neoplasms, castration, androgen receptor, hormonal, and chemotherapy. Emphasis is placed on published clinical studies in advanced prostate cancer therapeutics in the past 5 to 10 years. Also included in the review are novel hormonal agents targeting the androgen receptor currently in development for the treatment of advanced prostate cancer. PMID:20042563

  9. Oligometastatic prostate cancer: Metastases-directed therapy?

    PubMed

    Van Poppel, Hein; De Meerleer, Gert; Joniau, Steven

    2016-09-01

    Since the introduction of anatomical and functional imaging with multiparametric magnetic resonance imaging and choline or prostate-specific membrane antigen positron emission tomography-computed tomography, we are able to diagnose a previously unknown disease, the oligometastatic prostate cancer after local therapy. Reports on surgical and radiation treatment for low-volume metastatic recurrence have shown promising results, with definitive cure in few but a relevant delay of androgen-deprivation therapy with both treatment methods. Obviously, these results need to be validated with prospective randomised data. PMID:27547457

  10. 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

  11. Gene regulatory mechanisms underpinning prostate cancer susceptibility.

    PubMed

    Whitington, Thomas; Gao, Ping; Song, Wei; Ross-Adams, Helen; Lamb, Alastair D; Yang, Yuehong; Svezia, Ilaria; Klevebring, Daniel; Mills, Ian G; Karlsson, Robert; Halim, Silvia; Dunning, Mark J; Egevad, Lars; Warren, Anne Y; Neal, David E; Grönberg, Henrik; Lindberg, Johan; Wei, Gong-Hong; Wiklund, Fredrik

    2016-04-01

    Molecular characterization of genome-wide association study (GWAS) loci can uncover key genes and biological mechanisms underpinning complex traits and diseases. Here we present deep, high-throughput characterization of gene regulatory mechanisms underlying prostate cancer risk loci. Our methodology integrates data from 295 prostate cancer chromatin immunoprecipitation and sequencing experiments with genotype and gene expression data from 602 prostate tumor samples. The analysis identifies new gene regulatory mechanisms affected by risk locus SNPs, including widespread disruption of ternary androgen receptor (AR)-FOXA1 and AR-HOXB13 complexes and competitive binding mechanisms. We identify 57 expression quantitative trait loci at 35 risk loci, which we validate through analysis of allele-specific expression. We further validate predicted regulatory SNPs and target genes in prostate cancer cell line models. Finally, our integrated analysis can be accessed through an interactive visualization tool. This analysis elucidates how genome sequence variation affects disease predisposition via gene regulatory mechanisms and identifies relevant genes for downstream biomarker and drug development. PMID:26950096

  12. Circulating 25-Hydroxyvitamin D, Vitamin D Binding Protein, and Risk of Prostate Cancer

    PubMed Central

    Weinstein, Stephanie J.; Mondul, Alison M.; Kopp, William; Rager, Helen; Virtamo, Jarmo; Albanes, Demetrius

    2012-01-01

    We recently reported a significant positive association between 25-hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, and prostate cancer risk. To further elucidate this association, we examined the influence of vitamin D binding protein (DBP), the primary transporter of vitamin D compounds in the circulation. Prediagnostic serum concentrations of DBP were assayed for 950 cases and 964 matched controls with existing 25(OH)D measurements within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI), and statistical tests were two-sided. Serum DBP modified the association between serum 25(OH)D and prostate cancer, with higher risk for elevated 25(OH)D levels observed primarily among men having DBP concentrations above the median (OR=1.81, 95% CI 1.18–2.79 for highest vs. lowest quintile, p-trend = 0.001) compared to those with DBP below the median (OR=1.22, 95% CI 0.81–1.84, p-trend 0.97; p-interaction = 0.04). Serum DBP was not associated with prostate cancer risk overall (OR=0.96, 95% CI 0.70–1.33 for highest vs. lowest quintile); however, high serum DBP was associated with significantly decreased risk of prostate cancer in men with lower (prostate cancer. PMID:23180681

  13. Estimated phytanic acid intake and prostate cancer risk: a prospective cohort study.

    PubMed

    Wright, Margaret E; Bowen, Phyllis; Virtamo, Jarmo; Albanes, Demetrius; Gann, Peter H

    2012-09-15

    Phytanic acid is a saturated fatty acid found predominantly in red meat and dairy products and may contribute to increases in prostate cancer risk that are observed with higher intakes of these foods. We constructed a novel summary measure of phytanic acid intake and prospectively examined its association with prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study--a cohort of Finnish male smokers aged 50-69 years. Diet was assessed at baseline in 27,111 participants using a validated 276-item dietary questionnaire. Since phytanic acid is not currently included in food composition tables, we used the published phytanic acid content of 151 major food items to estimate total daily intake. During up to 21 years of follow-up, a total of 1,929 incident prostate cancer cases (including 438 advanced cases) were identified. Higher phytanic acid intake, though unrelated to the risk of localized disease [relative risks (RR) and 95% confidence intervals (CI) for increasing quartiles of intake = 1.00 (ref), 0.83 (0.68-1.01), 0.76 (0.62-0.94) and 0.91 (0.74-1.13); p trend = 0.23], was associated with increased risks of advanced prostate cancer [RR and 95% CI = 1.00 (ref), 1.43 (1.09-1.89), 1.31 (0.99-1.75) and 1.38 (1.02-1.89); p trend = 0.06]. This association appeared to be driven predominantly by phytanic acid obtained from dairy products (particularly butter). Our study indicates that phytanic acid may contribute to previously observed associations between high-fat animal foods (particularly dairy products) and prostate cancer risk, although some caution is warranted as it may be acting as a surrogate marker of dairy fat. PMID:22120496

  14. Estimated Phytanic Acid Intake and Prostate Cancer Risk: a Prospective Cohort Study

    PubMed Central

    Wright, Margaret E.; Bowen, Phyllis; Virtamo, Jarmo; Albanes, Demetrius; Gann, Peter H.

    2013-01-01

    Phytanic acid is a saturated fatty acid found predominantly in red meat and dairy products and may contribute to increases in prostate cancer risk that are observed with higher intakes of these foods. We constructed a novel summary measure of phytanic acid intake and prospectively examined its association with prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study – a cohort of Finnish male smokers ages 50–69 years. Diet was assessed at baseline in 27,111 participants using a validated 276-item dietary questionnaire. Since phytanic acid is not currently included in food composition tables, we used the published phytanic acid content of 151 major food items to estimate total daily intake. During up to 20 years of follow-up, a total of 1,929 incident prostate cancer cases (including 438 advanced cases) were identified. Higher phytanic acid intake, though unrelated to the risk of localized disease [relative risks and 95% confidence intervals for increasing quartiles of intake = 1.00 (ref), 0.83 (0.68–1.01), 0.76 (0.62–0.94), and 0.91 (0.74–1.13); p trend = 0.23], was associated with increased risks of advanced prostate cancer [RR and 95% CI = 1.00 (ref), 1.43 (1.09–1.89), 1.31 (0.99–1.75), and 1.38 (1.02–1.89); p trend = 0.06]. This association appeared to be driven predominantly by phytanic acid obtained from dairy products (particularly butter). Our study indicates that phytanic acid may contribute to previously observed associations between high-fat animal foods (particularly dairy products) and prostate cancer risk, although some caution is warranted as it may be acting as a surrogate marker of dairy fat. PMID:22120496

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

    ERIC Educational Resources Information Center

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

    2015-01-01

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

  16. African American Men and Prostate Cancer: Be Your Own Advocate and Understand Screening

    MedlinePlus

    ... the benefits of prostate cancer screening outweigh the harms. Some doctors screen some men for prostate cancer ... find prostate cancers that never would have caused harm in a man’s lifetime. In either case, screening ...

  17. Prostate Cancer: Symptoms, Diagnosis and Treatment | NIH MedlinePlus the Magazine

    MedlinePlus

    ... Javascript on. Feature: Prostate Cancer Prostate Cancer: Symptoms, Diagnosis and Treatment Past Issues / Winter 2010 Table of ... thighs Difficulty having an erection Pain with ejaculation Diagnosis Your healthcare provider can check for prostate cancer ...

  18. Finasteride Reduces the Risk of Low-Grade Prostate Cancer in Men 55 and Older

    MedlinePlus

    ... Genetics of Prostate Cancer Prostate Cancer Screening Research Finasteride Reduces the Risk of Low-Grade Prostate Cancer ... PCPT) continue to show that regular use of finasteride (Proscar®) for up to 7 years decreased the ...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. An unusual case of retrovesical ectopic prostate tissue accompanied by primary prostate cancer.

    PubMed

    Tan, Fu-Qing; Xu, Xin; Shen, Bo-Hua; Qin, Jie; Sun, Ke; You, Qihan; Shang, De-Sheng; Zheng, Xiang-Yi

    2012-01-01

    We report an unusual case of retrovesical ectopic prostate tissue in a 73-year-old man with primary prostate cancer. The man's prostate-specific antigen was 24.66 ng/ml.Transabdominal ultrasonography, pelvic computed tomography,and pelvic magnetic resonance imaging demonstrated a heterogeneous 8.5 × 8.0 × 7.0 cm mass in contact with the posterior wall of the urinary bladder. The patient underwent a retropubic radical prostatectomy and resection of tumor. Pathological examination of prostate revealed a prostatic adenocarcinoma, Gleason score of 4 + 5 = 9, and the retrovesical tumor was confirmed to be a benign prostate tissue. PMID:22966979

  1. EXAFS studies of prostate cancer cell lines

    NASA Astrophysics Data System (ADS)

    Czapla, J.; Kwiatek, W. M.; Lekki, J.; Kisiel, A.; Steininger, R.; Goettlicher, J.

    2013-04-01

    Sulphur plays a vital role in every human organism. It is known, that sulphur-bearing compounds, such as for example cysteine and glutathione, play critical roles in development and progression of many diseases. Any alteration in sulphur's biochemistry could become a precursor of serious pathological conditions. One of such condition is prostate cancer, the most frequently diagnosed malignancy in the western world and the second leading cause of cancer related death in men. The purpose of presented studies was to examine what changes occur in the nearest chemical environment of sulphur in prostate cancer cell lines in comparison to healthy cells. The Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy was used, followed by theoretical calculations. The results of preliminary analysis is presented.

  2. Prospective Evaluation of Operating Characteristics of Prostate Cancer Detection Biomarkers

    PubMed Central

    Liang, Yuanyuan; Ankerst, Donna P.; Ketchum, Norma S.; Ercole, Barbara; Shah, Girish; Shaughnessy, John D.; Leach, Robin J.; Thompson, Ian M.

    2016-01-01

    Purpose We assessed the independent predictive values of the serum markers free prostate specific antigen, proenzyme prostate specific antigen, neuroendocrine marker and Dickkopf-1 compared to serum prostate specific antigen and other standard risk factors for early prostate cancer detection. Materials and Methods From the prospectively collected SABOR cohort 250 prostate cancer cases, and 250 mean age matched and proportion of African-American race/ethnicity matched controls were selected who had a prior available prostate specific antigen and digital rectal examination. Serum samples were obtained, and free prostate specific antigen, [−2]proenzyme prostate specific antigen, Dickkopf-1 and neuroendocrine marker were measured. AUC, sensitivities and specificities were calculated, and multivariable logistic regression was used to assess the independent predictive value compared to prostate specific antigen, digital rectal examination, family history, prior biopsy history, race/ethnicity and age. Results The AUCs (95% CI) were 0.76 (0.71, 0.8) for free prostate specific antigen, 0.72 (0.67, 0.76) for [−2]proenzyme prostate specific antigen, 0.76 (0.72, 0.8) for %free prostate specific antigen, 0.61 (0.56, 0.66) for %[−2]proenzyme prostate specific antigen, 0.73 (0.68, 0.77) for prostate health index, 0.53 (0.48, 0.58) for Dickkopf-1 and 0.53 (0.48, 0.59) for neuroendocrine marker. In the 2 to 10 ng/ml prostate specific antigen range the AUCs (95% CI) were 0.58 (0.49, 0.67) for free prostate specific antigen, 0.53 (0.44, 0.62) for [−2]proenzyme prostate specific antigen, 0.67 (0.59, 0.75) for %free prostate specific antigen, 0.57 (0.49, 0.65) for %[−2]proenzyme prostate specific antigen and 0.59 (0.51, 0.67) for phi. Only %free prostate specific antigen retained independent predictive value compared to the traditional risk factors. Conclusions Free prostate specific antigen retained independent diagnostic usefulness for prostate cancers detected through

  3. 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

  4. Optimization of Radiation Therapy Techniques for Prostate Cancer With Prostate-Rectum Spacers: A Systematic Review

    SciTech Connect

    Mok, Gary; Benz, Eileen; Vallee, Jean-Paul; Miralbell, Raymond; Zilli, Thomas

    2014-10-01

    Dose-escalated radiation therapy for localized prostate cancer improves disease control but is also associated with worse rectal toxicity. A spacer placed between the prostate and rectum can be used to displace the anterior rectal wall outside of the high-dose radiation regions and potentially minimize radiation-induced rectal toxicity. This systematic review focuses on the published data regarding the different types of commercially available prostate-rectum spacers. Dosimetric results and preliminary clinical data using prostate-rectum spacers in patients with localized prostate cancer treated by curative radiation therapy are compared and discussed.

  5. New serum biomarkers for prostate cancer diagnosis

    PubMed Central

    Chadha, Kailash C.; Miller, Austin; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Underwood, Willie

    2014-01-01

    Background Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods Concurrent measurements of circulating interleukin-8 (IL-8), Tumor necrosis factor-α (TNF-α) and soluble tumor necrosis factor-α receptors 1 (sTNFR1) were obtained from four groups of men: (1) Controls (2) with elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx) (3) with clinically localized CaP and (4) with castration resistant prostate cancer. Results TNF-α Area under the receiver operating characteristic curve (AUC = 0.93) and sTNFR1 (AUC = 0.97) were strong predictors of elPSA_negBx (vs. CaP). The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC = 0.997). The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC = 0.992) and PSA (AUC = 0.963) levels. Conclusions The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in the larger cohort is warranted. PMID:25593898

  6. β-Adrenergic Receptor Signaling in Prostate Cancer

    PubMed Central

    Braadland, Peder Rustøen; Ramberg, Håkon; Grytli, Helene Hartvedt; Taskén, Kristin Austlid

    2015-01-01

    Enhanced sympathetic signaling, often associated with obesity and chronic stress, is increasingly acknowledged as a contributor to cancer aggressiveness. In prostate cancer, intact sympathetic nerves are critical for tumor formation, and sympathectomy induces apoptosis and blocks tumor growth. Perineural invasion, involving enrichment of intra-prostatic nerves, is frequently observed in prostate cancer and is associated with poor prognosis. β2-adrenergic receptor (ADRB2), the most abundant receptor for sympathetic signals in prostate luminal cells, has been shown to regulate trans-differentiation of cancer cells to neuroendocrine-like cells and to affect apoptosis, angiogenesis, epithelial–mesenchymal transition, migration, and metastasis. Epidemiologic studies have shown that use of β-blockers, inhibiting β-adrenergic receptor activity, is associated with reduced prostate cancer-specific mortality. In this review, we aim to present an overview on how β-adrenergic receptor and its downstream signaling cascade influence the development of aggressive prostate cancer, primarily through regulating neuroendocrine differentiation. PMID:25629002

  7. Demography and disease characteristics of prostate cancer in India

    PubMed Central

    Hariharan, Krishnamoorthy; Padmanabha, Venugopal

    2016-01-01

    Introduction: The incidence of prostate cancer has shown significant variation across the globe. Though the prevalence and characteristics of this disease have been extensively studied in many countries, data regarding the true incidence of prostate cancer in India is limited. Materials and Methods: MEDLINE publications from 1990 to 2014 were searched and reviewed and compiled to assess the demographic profile of prostate cancer in India and characteristics unique to this disease in India. Results: The limited data available on prostate cancer showed significant differences in incidence, precipitating factors, and disease characteristics of prostate cancer in India. Conclusions: Since India would be having more number of cases of prostate cancer than most others in the years to come, adequate population-based data regarding the demography and disease characteristics of this disease are of paramount importance in this country. PMID:27127351

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

  9. Metastatic Prostate Cancer to the Duodenum: A Rare Case

    PubMed Central

    Kaswala, Dharmesh H.; Patel, Nitin; Jadallah, Sana; Wang, Weizheng

    2014-01-01

    Prostate cancer is the third most common cancer in man. About 1 in 6 males developed prostate cancer and 1 in 35 males die of this disease. Prostate cancer behavior ranges from microscopic tumors to aggressive cancer with metastatic potential. While metastasis to bone is relatively common, prostate cancer rarely metastasizes to the cecum, pituitary gland, small bowel, maxillary sinus and skin. Our case report presents a rare presentation of metastatic prostate cancer to the duodenum. Our search of the literature found only 2 cases of prostate metastases to duodenum published from 1966 to the present. To our knowledge this is the third case of metastatic prostate cancer presenting with duodenal metastasis. Although it is rare but in symptomatic patients small intestine metastasis should not be ignored with advanced prostate cancer. The case demonstrates a novel presentation of a common malignancy, and should raise awareness in clinicians and radiologists that prostate cancer can present with distant metastases in absence of any local lymphadenopathy. PMID:25161979

  10. Hypofractionated External-Beam Radiotherapy for Prostate Cancer

    PubMed Central

    Cho, L. Chinsoo; Timmerman, Robert; Kavanagh, Brian

    2013-01-01

    There are radiobiological rationales supporting hypofractionated radiotherapy for prostate cancer. The recent advancements in treatment planning and delivery allow sophisticated radiation treatments to take advantage of the differences in radiobiology of prostate cancer and the surrounding normal tissues. The preliminary results from clinical studies indicate that abbreviated fractionation programs can result in successful treatment of localized prostate cancer without escalation of late toxicity. PMID:23533777

  11. Port site metastasis in prostate cancer.

    PubMed

    De Bruyne, Peter; Schatteman, Peter; De Naeyer, Geert; Carpentier, Paul; Mottrie, Alex

    2015-01-01

    Port-site metastasis of prostatic adenocarcinoma is rare and usually associated with poor prognosis. We report a case of a young man with a rising prostate-specific antigen (PSA) 4.5 years after robot-assisted laparoscopic prostatectomy (RALP) and extended pelvic lymphadenectomy (ePLND) for a Gleason 7 (4+3) prostate cancer (pT3b pN0 cM0). Choline positron emission tomography-computed tomography (PET-CT) demonstrated a PET positive subcutaneous recurrence in a previous trocar site accompanied by a PET positive ipsilateral inguinal lymph node. Excision of both lesions was performed, confirming the diagnosis of metastatic prostate cancer. The patient's PSA dropped significantly postoperatively enabling postponement of androgen deprivation treatment up to this date. The etiology of port-site metastasis is multifactorial, including patient and surgery related factors. Such metastases have been scarcely reported following ePLND with or without RALP. Certain surgical precautions can be made to prevent the occurrence. We summarize previously reported mechanisms of development and possible precautionary measures. PMID:26225184

  12. A Genome-wide Pleiotropy Scan for Prostate Cancer Risk

    PubMed Central

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

    2014-01-01

    Background No single-nucleotide polymorphisms (SNPs) specific for aggressive prostate cancer have been identified in genome-wide association studies (GWAS). Objective To test if SNPs associated with other traits may also affect the risk of aggressive prostate cancer. Design, setting, and participants SNPs implicated in any phenotype other than prostate cancer (p ≤ 10−7) were identified through the catalog of published GWAS and tested in 2891 aggressive prostate cancer cases and 4592 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). The 40 most significant SNPs were followed up in 4872 aggressive prostate cancer cases and 24 534 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Outcome measurements and statistical analysis Odds ratios (ORs) and 95% confidence intervals (CIs) for aggressive prostate cancer were estimated. Results and limitations A total of 4666 SNPs were evaluated by the BPC3. Two signals were seen in regions already reported for prostate cancer risk. rs7014346 at 8q24.21 was marginally associated with aggressive prostate cancer in the BPC3 trial (p = 1.6 × 10-6), whereas after meta-analysis by PRACTICAL the summary OR was 1.21 (95%CI 1.16–1.27; p = 3.22 × 10−18). rs9900242 at 17q24.3 was also marginally associated with aggressive disease in the meta-analysis (OR 0.90, 95% CI 0.86–0.94; p = 2.5 × 10−6). Neither of these SNPs remained statistically significant when conditioning on correlated known prostate cancer SNPs. The meta-analysis by BPC3 and PRACTICAL identified a third promising signal, marked by rs16844874 at 2q34, independent of known prostate cancer loci (OR 1.12,95% CI 1.06–1.19; p = 4.67 × 10−5); it has been shown that SNPs correlated with this signal affect glycine concentrations. The main limitation is the heterogeneity in the definition of aggressive prostate cancer between BPC3 and PRACTICAL. Conclusions We did

  13. Integrative clinical genomics of advanced prostate cancer.

    PubMed

    Robinson, Dan; Van Allen, Eliezer M; Wu, Yi-Mi; Schultz, Nikolaus; Lonigro, Robert J; Mosquera, Juan-Miguel; Montgomery, Bruce; Taplin, Mary-Ellen; Pritchard, Colin C; Attard, Gerhardt; Beltran, Himisha; Abida, Wassim; Bradley, Robert K; Vinson, Jake; Cao, Xuhong; Vats, Pankaj; Kunju, Lakshmi P; Hussain, Maha; Feng, Felix Y; Tomlins, Scott A; Cooney, Kathleen A; Smith, David C; Brennan, Christine; Siddiqui, Javed; Mehra, Rohit; Chen, Yu; Rathkopf, Dana E; Morris, Michael J; Solomon, Stephen B; Durack, Jeremy C; Reuter, Victor E; Gopalan, Anuradha; Gao, Jianjiong; Loda, Massimo; Lis, Rosina T; Bowden, Michaela; Balk, Stephen P; Gaviola, Glenn; Sougnez, Carrie; Gupta, Manaswi; Yu, Evan Y; Mostaghel, Elahe A; Cheng, Heather H; Mulcahy, Hyojeong; True, Lawrence D; Plymate, Stephen R; Dvinge, Heidi; Ferraldeschi, Roberta; Flohr, Penny; Miranda, Susana; Zafeiriou, Zafeiris; Tunariu, Nina; Mateo, Joaquin; Perez-Lopez, Raquel; Demichelis, Francesca; Robinson, Brian D; Schiffman, Marc; Nanus, David M; Tagawa, Scott T; Sigaras, Alexandros; Eng, Kenneth W; Elemento, Olivier; Sboner, Andrea; Heath, Elisabeth I; Scher, Howard I; Pienta, Kenneth J; Kantoff, Philip; de Bono, Johann S; Rubin, Mark A; Nelson, Peter S; Garraway, Levi A; Sawyers, Charles L; Chinnaiyan, Arul M

    2015-05-21

    Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals. PMID:26000489

  14. Integrative clinical genomics of advanced prostate cancer

    PubMed Central

    Dan, Robinson; Van Allen, Eliezer M.; Wu, Yi-Mi; Schultz, Nikolaus; Lonigro, Robert J.; Mosquera, Juan-Miguel; Montgomery, Bruce; Taplin, Mary-Ellen; Pritchard, Colin C; Attard, Gerhardt; Beltran, Himisha; Abida, Wassim M.; Bradley, Robert K.; Vinson, Jake; Cao, Xuhong; Vats, Pankaj; Kunju, Lakshmi P.; Hussain, Maha; Feng, Felix Y.; Tomlins, Scott A.; Cooney, Kathleen A.; Smith, David C.; Brennan, Christine; Siddiqui, Javed; Mehra, Rohit; Chen, Yu; Rathkopf, Dana E.; Morris, Michael J.; Solomon, Stephen B.; Durack, Jeremy C.; Reuter, Victor E.; Gopalan, Anuradha; Gao, Jianjiong; Loda, Massimo; Lis, Rosina T.; Bowden, Michaela; Balk, Stephen P.; Gaviola, Glenn; Sougnez, Carrie; Gupta, Manaswi; Yu, Evan Y.; Mostaghel, Elahe A.; Cheng, Heather H.; Mulcahy, Hyojeong; True, Lawrence D.; Plymate, Stephen R.; Dvinge, Heidi; Ferraldeschi, Roberta; Flohr, Penny; Miranda, Susana; Zafeiriou, Zafeiris; Tunariu, Nina; Mateo, Joaquin; Lopez, Raquel Perez; Demichelis, Francesca; Robinson, Brian D.; Schiffman, Marc A.; Nanus, David M.; Tagawa, Scott T.; Sigaras, Alexandros; Eng, Kenneth W.; Elemento, Olivier; Sboner, Andrea; Heath, Elisabeth I.; Scher, Howard I.; Pienta, Kenneth J.; Kantoff, Philip; de Bono, Johann S.; Rubin, Mark A.; Nelson, Peter S.; Garraway, Levi A.; Sawyers, Charles L.; Chinnaiyan, Arul M.

    2015-01-01

    SUMMARY Toward development of a precision medicine framework for metastatic, castration resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53 and PTEN were frequent (40–60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified novel genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin and ZBTB16/PLZF. Aberrations of BRCA2, BRCA1 and ATM were observed at substantially higher frequencies (19.3% overall) than seen in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides evidence that clinical sequencing in mCRPC is feasible and could impact treatment decisions in significant numbers of affected individuals. PMID:26000489

  15. Prostate Cancer Severity Associations with Neighborhood Deprivation

    PubMed Central

    Zeigler-Johnson, Charnita M.; Tierney, Ann; Rebbeck, Timothy R.; Rundle, Andrew

    2011-01-01

    Background. The goal of this paper was to examine neighborhood deprivation and prostate cancer severity. Methods. We studied African American and Caucasian prostate cancer cases from the Pennsylvania State Cancer Registry. Census tract-level variables and deprivation scores were examined in relation to diagnosis stage, grade, and tumor aggressiveness. Results. We observed associations of low SES with high Gleason score among African Americans residing in neighborhoods with low educational attainment (OR = 1.34, 95% CI = 1.13–1.60), high poverty (OR = 1.39, 95% CI = 1.15–1.67), low car ownership (OR = 1.46, 95% CI = 1.20–1.78), and higher percentage of residents on public assistance (OR = 1.32, 95% = 1.08–1.62). The highest quartile of neighborhood deprivation was also associated with high Gleason score. For both Caucasians and African Americans, the highest quartile of neighborhood deprivation was associated with high Gleason score at diagnosis (OR = 1.34, 95% CI = 1.19–1.52; OR = 1.71, 95% CI = 1.21–2.40, resp.). Conclusion. Using a neighborhood deprivation index, we observed associations between high-grade prostate cancer and neighborhood deprivation in Caucasians and African-Americans. PMID:22111000

  16. 75 FR 54453 - National Prostate Cancer Awareness Month, 2010

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-07

    .... (Presidential Sig.) [FR Doc. 2010-22429 Filed 9-3-10; 11:15 am] Billing code 3195-W0-P ... Documents#0;#0; ] Proclamation 8552 of August 31, 2010 National Prostate Cancer Awareness Month, 2010 By the... the last decade, prostate cancer is still the second leading cause of cancer deaths among men in...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  18. Epigenetics in Breast and Prostate Cancer

    PubMed Central

    Wu, Yanyuan; Sarkissyan, Marianna; Vadgama, Jaydutt V.

    2015-01-01

    SUMMARY Most recent investigations into cancer etiology have identified a key role played by epigenetics. Specifically, aberrant DNA and histone modifications which silence tumor suppressor genes or promote oncogenes have been demonstrated in multiple cancer models. While the role of epigenetics in several solid tumor cancers such as colorectal cancer are well established, there is emerging evidence that epigenetics also plays a critical role in breast and prostate cancer. In breast cancer, DNA methylation profiles have been linked to hormone receptor status and tumor progression. Similarly in prostate cancer, epigenetic patterns have been associated with androgen receptor status and response to therapy. The regulation of key receptor pathways and activities which affect clinical therapy treatment options by epigenetics renders this field high priority for elucidating mechanisms and potential targets. A new set of methylation arrays are now available to screen epigenetic changes and provide the cuttingedge tools needed to perform such investigations. The role of nutritional interventions affecting epigenetic changes particularly holds promise. Ultimately, determining the causes and outcomes from epigenetic changes will inform translational applications for utilization as biomarkers for risk and prognosis as well as candidates for therapy. PMID:25421674

  19. Resveratrol–zinc combination for prostate cancer management

    PubMed Central

    Singh, Chandra K; Pitschmann, Anna; Ahmad, Nihal

    2014-01-01

    Zinc, an essential trace element, plays a critical role in cell signaling, and defect(s) in zinc homeostasis may contribute to adverse physiological and pathological conditions, including cancer. Zinc is present in healthy prostate at a very high concentration, where it is required for important prostatic functions. However, zinc levels are significantly diminished in cancerous tissue, and intracellular zinc level is inversely correlated with prostate cancer progression. During neoplastic transformation, zinc-accumulating, citrate-producing normal prostate cells are metabolically transformed to citrate oxidizing cells that lose the ability to accumulate zinc. Interestingly, zinc has been shown to function as chemopreventive agent against prostate cancer, albeit at high doses, which may lead to many adverse effects. Therefore, novel means to enhance bioaccumulation of sufficient zinc in prostate cells via increasing zinc transport could be useful against prostate cancer. On the basis of available evidence, we present a possibility that the grape antioxidant resveratrol, when given with zinc, may lead to retuning the zinc homeostasis in prostate, thereby abolishing or reversing malignancy. If experimentally verified in in vivo model(s) of prostate cancer, such as transgenic mouse models, this may lead to novel means toward management of prostate cancer and other conditions with compromised zinc homeostasis. PMID:24866157

  20. 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

  1. Resveratrol-zinc combination for prostate cancer management.

    PubMed

    Singh, Chandra K; Pitschmann, Anna; Ahmad, Nihal

    2014-01-01

    Zinc, an essential trace element, plays a critical role in cell signaling, and defect(s) in zinc homeostasis may contribute to adverse physiological and pathological conditions, including cancer. Zinc is present in healthy prostate at a very high concentration, where it is required for important prostatic functions. However, zinc levels are significantly diminished in cancerous tissue, and intracellular zinc level is inversely correlated with prostate cancer progression. During neoplastic transformation, zinc-accumulating, citrate-producing normal prostate cells are metabolically transformed to citrate oxidizing cells that lose the ability to accumulate zinc. Interestingly, zinc has been shown to function as chemopreventive agent against prostate cancer, albeit at high doses, which may lead to many adverse effects. Therefore, novel means to enhance bioaccumulation of sufficient zinc in prostate cells via increasing zinc transport could be useful against prostate cancer. On the basis of available evidence, we present a possibility that the grape antioxidant resveratrol, when given with zinc, may lead to retuning the zinc homeostasis in prostate, thereby abolishing or reversing malignancy. If experimentally verified in in vivo model(s) of prostate cancer, such as transgenic mouse models, this may lead to novel means toward management of prostate cancer and other conditions with compromised zinc homeostasis. PMID:24866157

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

    PubMed Central

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

    2014-01-01

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

  3. From Inflammation to Prostate Cancer: The Role of Inflammasomes

    PubMed Central

    Dubey, Seema

    2016-01-01

    Inflammation-associated studies entice specific attention due to inflammation's role in multiple stages of prostate cancer development. However, mechanistic regulation of inflammation inciting prostate cancer remains largely uncharacterized. A focused class of inflammatory regulators known as inflammasomes has recently gained attention in cancer development. Inflammasomes are a multiprotein complex that drives a cascade of proinflammatory cytokines regulating various cellular activities. Inflammasomes activation is linked with infection, stress, or danger signals, which are common events within the prostate gland. In this study, we review the potential of inflammasomes in understanding the role of inflammation in prostate cancer. PMID:27429614

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

    PubMed Central

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

    2013-01-01

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

  5. 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

  6. Fortifying the Treatment of Prostate Cancer with Physical Activity.

    PubMed

    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

  7. Prostate cancer and glutathione S-transferase deletions

    PubMed Central

    Malik, Saima Shakil; Masood, Nosheen; Yasmin, Azra

    2015-01-01

    GSTM1 and GSTT1 gene polymorphisms have been studied in many populations to evaluate their association with prostate cancer risk with contrasting results. The current study was aimed to find out the association of GSTM1 and GSTT1 gene polymorphisms with prostate cancer in Pakistani men. This case control study included pathologically confirmed prostate cancer patients and age matched male controls. Epidemiological data was collected by a standard questionnaire and presence or absence of GSTM1 and GSTT1 gene was observed by multiplex PCR using CYP1A1 as housekeeping gene. Prostate cancer was more prevalent in age of >60 years and most of the patients were at stage IV (70 %) and have undergone surgery. Family history of cancer, smoking, metastasis and surgery were found to be significant (P<0.05) risk factors in prostate cancer development. Gleason score 7 was most prevalent (40.5 %) in prostate cancer patients. Source of drinking water, residential area, occupation, eating habits and number of family members had no association (P>0.05) with prostate cancer risk. No significant association was found when comparing GSTM1 (OR=0.78) and GSTT1 (OR=0.89) gene deletions with prostate cancer risk. Smoking and TNM staging were also not associated with deletion of GSTM1 and GSTT1 genes. Comparison of dual null deletion of both genes with prostate cancer also showed non-significant associations. Deletion of GSTM1 gene at stage IV prostate cancer patients was significantly higher compared with other stages of cancer while no significance was shown by GSTT1 gene deletion. GSTM1, GSTT1 and deletion of both GSTM1 and GSTT1 genes do not contribute towards increased risk of prostate cancer in Pakistani population. PMID:26600754

  8. Genomic approaches to outcome prediction in prostate cancer.

    PubMed

    Febbo, Phillip G

    2009-07-01

    Prostate cancer remains a common cause of cancer death in men. Applications of emerging genomic technologies to high-quality prostate cancer models and patient samples in multiple contexts have made significant contributions to our molecular understanding of the development and progression of prostate cancer. Genomic analysis of DNA, RNA, and protein alterations allows for the global assessment of this disease and provides the molecular framework to improve risk classification, outcome prediction, and development of targeted therapies. In this review, the author focused on highlighting recent work in genomics and its role in evaluating molecular modifiers of prostate cancer risk and behavior and the development of predictive models that anticipate the risk of developing prostate cancer, prostate cancer progression, and the response of prostate cancer to therapy. This framework has the exciting potential to be predictive and to provide personalized and individual treatment to the large number of men diagnosed with prostate cancer each year. Cancer 2009;115(13 suppl):3046-57. (c) 2009 American Cancer Society. PMID:19544546

  9. Europa Uomo: the European Prostate Cancer Coalition.

    PubMed

    Hudson, Tom; Denis, Louis J

    2007-01-01

    Europa Uomo is a patient-led, non-governmental association (NGO), launched formally in Milan in 2004 with a legal base in Antwerp. As a coalition of prostate cancer patient groups with representation in 18 European countries, the NGO focusses on awareness, early detection, optimal treatment, multi-professional care and, above all, quality of life and patient advocacy. In the majority of European countries prostate cancer is the most commonly diagnosed cancer affecting men beyond middle age. The incidence and substantial mortality rises with age, peaking in the seventh decade. Standards of diagnosis and treatment vary across Europe and attitudes differ. Information about the early detection and awareness of prostate cancer available to the public leaves much to be desired. Since 2002, involved individuals, patient support groups, patients, family members, physicians, urologists, oncologists and nurses joined in the formation of an independent, international, non-profit association of patient-led prostate cancer support groups from European countries known as Europa Uomo, the European Prostate Cancer Coalition. This Coalition was legally established as an NGO in June 2004 in Milan with the headquarters and secretariat in Antwerp, Belgium. Its membership represents 18 countries by the national or regional groups listed in Table 16.1 with their respective contact persons. The coalition is led by a steering committee under the control of the annual general assembly. The steering committee members and their co-ordinates are listed in Table 16.2. Scientific advice is given by a scientific committee chaired by Prof. H. Van Poppel as the liaison officer with the European Association of Urology (EAU). The support for EAU guidelines appears on the Web site and will be linked to all members in their own language (www.cancerworld.org/europauomo). The goals and activities of Europa Uomo have been condensed in a series of slides at the request of the Eurocan+Plus collaboration to

  10. [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

  11. Ureteral Metastasis Secondary to Prostate Cancer: A Case Report.

    PubMed

    Morales, I; Bassa, C; Pavlovic, A; Morales, C

    2016-03-01

    Prostate cancer is very frequent, but secondary ureteral metastasis are extremely rare. We present a 55 year old man with a 2 month history of right flank pain and lower urinary tract symptoms. Prostatic specific antigen of 11.3 ng/mL. Computed tomography showed right hydroureteronephrosis, a developing urinoma and right iliac adenopathies. He underwent right ureteronephrectomy, iliac lymphadenectomy and prostate biopsy. Pathology revealed prostatic carcinoma infiltrating the ureteral muscularis propria, without mucosal involvement. There are 46 reported cases of prostate cancer with ureteral metastases. Ureteral metastasis are a rare cause of renal colic and need of a high index of suspicion. PMID:26793587

  12. Ureteral Metastasis Secondary to Prostate Cancer: A Case Report

    PubMed Central

    Morales, I.; Bassa, C.; Pavlovic, A.; Morales, C.

    2015-01-01

    Prostate cancer is very frequent, but secondary ureteral metastasis are extremely rare. We present a 55 year old man with a 2 month history of right flank pain and lower urinary tract symptoms. Prostatic specific antigen of 11.3 ng/mL. Computed tomography showed right hydroureteronephrosis, a developing urinoma and right iliac adenopathies. He underwent right ureteronephrectomy, iliac lymphadenectomy and prostate biopsy. Pathology revealed prostatic carcinoma infiltrating the ureteral muscularis propria, without mucosal involvement. There are 46 reported cases of prostate cancer with ureteral metastases. Ureteral metastasis are a rare cause of renal colic and need of a high index of suspicion. PMID:26793587

  13. A recommender system for prostate cancer websites.

    PubMed

    Witteman, Holly; Chignell, Mark; Krahn, Murray

    2008-01-01

    One of the challenges for people seeking health information online is the difficulty in locating health Websites that are personally relevant, credible and useful. We developed a Web-based recommender system in order to help address this problem in the context of prostate cancer. We are conducting an online randomized controlled trial to evaluate the accuracy of its recommendations and to compare the efficacy of content-based and collaborative filtering. PMID:18999034

  14. [Metastatic hormone-sensitive prostate cancer].

    PubMed

    Gravis, Gwenaelle; Salem, Naji; Walz, Jochen

    2015-01-01

    The prostate cancer in its hormone-sensitive metastatic presentation is infrequent, it is either an initial presentation of the disease or an evolution after local treatment, without castration of the biological relapse. The surgical or biological castration remains the cornerstone of the treatment. The deadline of castration initiation and its modalities of administration, intermittent or continuous rest debated but consensual on the initiation is the appearance of the symptomatic disease. The chemotherapy by docetaxel in association with the castration increases significantly the survival of the patients having a high tumoral volume. The efficacy on the whole metastatic population requires additional analyses. Clinical prognostic factors as the bone localizations (axial or appendicular), the visceral involvement (liver, lung) are determining for the survival of these patients. Biological prognostic factors are in evaluation. Except the clodronate acid, which showed a survival improvement in the hormone-sensitive metastatic prostate cancer (HSMPC), the other treatments targeting the bone (zoledronic acid, rank-ligand inhibitor) demonstrated a benefit only in castrate resistant metastatic prostate cancer (MCRPC). The management of local disease lets suggest a benefit to at least symptomatic disease, but it requires to be estimated prospectively in clinical trials. The new hormonal treatments targeting the androgen receptor in CPMRC are in evaluation in CPMHS. The objective is to increase the survival and the quality of life of the CPMHS and to delay the evolution towards the castration resistant metastatic disease. PMID:25609491

  15. Upfront Chemotherapy for Metastatic Prostate Cancer.

    PubMed

    Lam, Elaine T; Flaig, Thomas W

    2015-12-01

    Traditionally, androgen deprivation therapy (ADT) has been the standard initial treatment for metastatic hormone-sensitive prostate cancer (mHSPC), with chemotherapy utilized in the castration-resistant setting. Data reported from three recent clinical trials shed new light on the role of upfront docetaxel in advanced or mHSPC. Two of these studies-CHAARTED and STAMPEDE-showed significant improvement in overall survival, while the third study, GETUG-AFU 15, showed no statistical difference. The CHAARTED study showed a 13.6-month survival improvement and the STAMPEDE study showed a 10-month survival improvement with ADT plus docetaxel, compared with ADT alone, in the hormone-sensitive setting. These numbers are remarkable when compared with the 2.9-month survival benefit from docetaxel in the metastatic castration-resistant setting, which has been the standard setting for the use of docetaxel in advanced prostate cancer. In this review, we describe the historical data for chemotherapy in the perioperative and metastatic prostate cancer settings, and the recent trials that are changing the paradigm in support of docetaxel in the upfront setting. PMID:26676900

  16. Insights into Chemoresistance of Prostate Cancer

    PubMed Central

    Zhang, Wei; Meng, Yan; Liu, Na; Wen, Xiao-Fei; Yang, Tao

    2015-01-01

    Prostate cancer (PCa) remains the most prevalent malignancy among males in the western world. Though hormonal therapies through chemical or surgical castration have been proposed many years ago, heretofore, such mainstay for the treatment on advanced PCa has not fundamentally changed. These therapeutic responses are temporary and most cases will eventually undergo PCa recurrence and metastasis, or even progress to castration-resistant prostate cancer (CRPC) due to persistent development of drug resistance. Prostate cancer stem cells (PCSCs) are a small population of cells, which possess unlimited self-renewal capacities, and can regenerate tumorigenic progenies, and play an essential role in PCa therapy resistance, metastasis and recurrence. Nowadays advanced progresses have been made in understanding of PCSC properties, roles of androgen receptor signaling and ATP-binding cassette sub-family G member 2 (ABCG2), as well as roles of genomic non-coding microRNAs and key signaling pathways, which have led to the development of novel therapies which are active against chemoresistant PCa and CRPC. Based on these progresses, this review is dedicated to address mechanisms underlying PCa chemoresistance, unveil crosstalks among pivotal signaling pathways, explore novel biotherapeutic agents, and elaborate functional properties and specific roles of chemoresistant PCSCs, which may act as a promising target for novel therapies against chemoresistant PCa. PMID:26327810

  17. 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

  18. Palliative Radiofrequency Ablation for Recurrent Prostate Cancer

    SciTech Connect

    Jindal, Gaurav; Friedman, Marc; Locklin, Julia Wood, Bradford J.

    2006-06-15

    Percutaneous radiofrequency ablation (RFA) is a minimally invasive local therapy for cancer. Its efficacy is now becoming well documented in many different organs, including liver, kidney, and lung. The goal of RFA is typically complete eradication of a tumor in lieu of an invasive surgical procedure. However, RFA can also play an important role in the palliative care of cancer patients. Tumors which are surgically unresectable and incompatible for complete ablation present the opportunity for RFA to be used in a new paradigm. Cancer pain runs the gamut from minor discomfort relieved with mild pain medication to unrelenting suffering for the patient, poorly controlled by conventional means. RFA is a tool which can potentially palliate intractable cancer pain. We present here a case in which RFA provided pain relief in a patient with metastatic prostate cancer with pain uncontrolled by conventional methods.

  19. Targeted prostate biopsy and MR-guided therapy for prostate cancer.

    PubMed

    Woodrum, David A; Kawashima, Akira; Gorny, Krzysztof R; Mynderse, Lance A

    2016-05-01

    Prostate cancer is the most commonly diagnosed noncutaneous cancer and second-leading cause of death in men. Many patients with clinically organ-confined prostate cancer undergo definitive treatment of the whole gland including radical prostatectomy, radiation therapy, and cryosurgery. Active surveillance is a growing alternative option for patients with documented low-volume, low-grade prostate cancer. With recent advances in software and hardware of MRI, multiparametric MRI of the prostate has been shown to improve the accuracy in detecting and characterizing clinically significant prostate cancer. Targeted biopsy is increasingly utilized to improve the yield of MR-detected, clinically significant prostate cancer and to decrease in detection of indolent prostate cancer. MR-guided targeted biopsy techniques include cognitive MR fusion TRUS biopsy, in-bore transrectal targeted biopsy using robotic transrectal device, and in-bore direct MR-guided transperineal biopsy with a software-based transperineal grid template. In addition, advances in MR compatible thermal ablation technology allow accurate focal or regional delivery of optimal thermal energy to the biopsy-proved, MRI-detected tumor, utilizing cryoablation, laser ablation, high-intensity focused ultrasound ablation under MR guidance and real-time or near simultaneous monitoring of the ablation zone. Herein we present a contemporary review of MR-guided targeted biopsy techniques of MR-detected lesions as well as MR-guided focal or regional thermal ablative therapies for localized naïve and recurrent cancerous foci of the prostate. PMID:26907717

  20. Prostate cancer, Hu antibodies and paraneoplastic neurological syndromes.

    PubMed

    Storstein, A; Raspotnig, M; Vitaliani, R; Giometto, B; Graus, F; Grisold, W; Honnorat, J; Vedeler, C A

    2016-05-01

    Prostate cancer is the most common cancer among American and European men. Nervous system affection caused by local tumor growth or osseous metastases are the main causes of neurological symptoms in prostate cancer patients. Prostate cancer is rarely reported in association with paraneoplastic neurological syndromes (PNS). We have, therefore, studied clinical and paraclinical findings of a series of patients with prostate cancer and PNS, and reviewed cases reported in the literature. Case histories of 14 patients with definite PNS from the PNS Euronetwork database and from the authors' databases were reviewed. A PubMed literature search identified 23 patients with prostate cancer and PNS. Thus, a total of 37 case histories were reviewed with respect to syndrome type, cancer evolution, paraclinical investigations, antibody status, treatment and outcome. The three most frequent isolated PNS were paraneoplastic cerebellar degeneration, paraneoplastic encephalomyelitis (PEM)/limbic encephalitis and subacute sensory neuronopathy (SSN). Onconeural antibodies were detected in 23 patients, in most cases the Hu antibody (17 patients, 74 % of all antibody-positive cases). Other well-characterized onconeural antibodies (Yo, CV2/CRMP5, amphiphysin, VGCC antibodies) were found in a minority. PNS was diagnosed prior to prostate cancer diagnosis in 50 % of the cases. The association of PNS with prostate cancer is quite infrequent, but clinically important. PNS often heralds prostate cancer diagnosis. Syndromes associated with Hu antibodies predominate. Another tumor more prone to associate with PNS should always be excluded. PMID:27007485

  1. Germline Mutations in HOXB13 and Prostate-Cancer Risk

    PubMed Central

    Ewing, Charles M.; Ray, Anna M.; Lange, Ethan M.; Zuhlke, Kimberly A.; Robbins, Christiane M.; Tembe, Waibhav D.; Wiley, Kathleen E.; Isaacs, Sarah D.; Johng, Dorhyun; Wang, Yunfei; Bizon, Chris; Yan, Guifang; Gielzak, Marta; Partin, Alan W.; Shanmugam, Vijayalakshmi; Izatt, Tyler; Sinari, Shripad; Craig, David W.; Zheng, S. Lilly; Walsh, Patrick C.; Montie, James E.; Xu, Jianfeng; Carpten, John D.; Isaacs, William B.; Cooney, Kathleen A.

    2013-01-01

    BACKGROUND Family history is a significant risk factor for prostate cancer, although the molecular basis for this association is poorly understood. Linkage studies have implicated chromosome 17q21-22 as a possible location of a prostate-cancer susceptibility gene. METHODS We screened more than 200 genes in the 17q21-22 region by sequencing germline DNA from 94 unrelated patients with prostate cancer from families selected for linkage to the candidate region. We tested family members, additional case subjects, and control subjects to characterize the frequency of the identified mutations. RESULTS Probands from four families were discovered to have a rare but recurrent mutation (G84E) in HOXB13 (rs138213197), a homeobox transcription factor gene that is important in prostate development. All 18 men with prostate cancer and available DNA in these four families carried the mutation. The carrier rate of the G84E mutation was increased by a factor of approximately 20 in 5083 unrelated subjects of European descent who had prostate cancer, with the mutation found in 72 subjects (1.4%), as compared with 1 in 1401 control subjects (0.1%) (P = 8.5×10−7). The mutation was significantly more common in men with early-onset, familial prostate cancer (3.1%) than in those with late-onset, nonfamilial prostate cancer (0.6%) (P = 2.0×10−6). CONCLUSIONS The novel HOXB13 G84E variant is associated with a significantly increased risk of hereditary prostate cancer. Although the variant accounts for a small fraction of all prostate cancers, this finding has implications for prostate-cancer risk assessment and may provide new mechanistic insights into this common cancer. (Funded by the National Institutes of Health and others.) PMID:22236224

  2. Prostate Cancer in Young Men: An Important Clinical Entity

    PubMed Central

    Salinas, Claudia A.; Tsodikov, Alex; Ishak-Howard, Miriam; Cooney, Kathleen A.

    2014-01-01

    Prostate cancer is considered a disease of older men, but today over 10% of new diagnoses occur in U.S. men ≤ 55 years. Early onset prostate cancer, i.e., diagnosed at ≤55 years, differs from prostate cancer in older men in several ways. Among men diagnosed with high grade and stage prostate cancer, men with early onset prostate cancer are more likely to die of their cancer, with higher cause-specific mortality than all others except those diagnosed over age 80. This suggests that important biological differences may exist in early onset disease compared to late onset disease. Furthermore, early onset prostate cancer has been shown to have a more significant genetic component indicating that this group may benefit more than most from evaluation of genetic risk. Clinically, although the majority of cases ≤ 55 years are diagnosed with low risk disease, their extended life expectancy exposes them to long-term risk of disease progression resulting in death from prostate cancer, but also to prolonged impact from treatment-related morbidities. These patients pose unique challenges and opportunities for both the research and clinical communities. We therefore suggest that early onset prostate cancer is a distinct phenotype, from both an etiologic and clinical perspective, that deserves further attention. PMID:24818853

  3. Growth factors mediated cell signalling in prostate cancer progression: Implications in discovery of anti-prostate cancer agents.

    PubMed

    Joshi, Gaurav; Singh, Pankaj Kumar; Negi, Arvind; Rana, Anil; Singh, Sandeep; Kumar, Raj

    2015-10-01

    Cancer is one of the leading causes of mortality amongst world's population, in which prostate cancer is one of the most encountered malignancies among men. Globally, it is the sixth leading cause of cancer-related death in men. Prostate cancer is more prevalent in the developed world and is increasing at alarming rates in the developing countries. Prostate cancer is mostly a very sluggish progressing disease, caused by the overproduction of steroidal hormones like dihydrotestosterone or due to over-expression of enzymes such as 5-α-reductase. Various studies have revealed that growth factors play a crucial role in the progression of prostate cancer as they act either by directly elevating the level of steroidal hormones or upregulating enzyme efficacy by the active feedback mechanism. Presently, treatment options for prostate cancer include radiotherapy, surgery and chemotherapy. If treatment is done with prevailing traditional chemotherapy; it leads to resistance and development of androgen-independent prostate cancer that further complicates the situation with no cure option left. The current review article is an attempt to cover and establish an understanding of some major signalling pathways intervened through survival factors (IGF-1R), growth factors (TGF-α, EGF), Wnt, Hedgehog, interleukin, cytokinins and death factor receptor which are frequently dysregulated in prostate cancer. This will enable the researchers to design and develop better therapeutic strategies targeting growth factors and their cross talks mediated prostate cancer cell signalling. PMID:26297992

  4. Prostate specific antigen density for discriminating prostate cancer from benign prostatic hyperplasia in the gray zone of prostate-specific antigen.

    PubMed

    Uno, H; Koide, T; Kuriyama, M; Ban, Y; Deguchi, T; Kawada, Y

    1999-07-01

    Serum prostate specific antigen (PSA) is currently the best blood marker for prostate cancer. However, low specificity for detection of prostate cancer, especially in the gray zone of PSA, is a problem. We evaluated the clinical significance of PSA density (PSAD) in gray zone PSA cases with conversion of serum PSA to a Stanford reference value. In a series of histologically confirmed 63 benign prostatic hyperplasia (BPH) patients and 234 prostate cancer patients, 36 BPH patients and 25 prostate cancer patients had gray zone PSA levels. Serum PSA was measured with the Markit-F or Markit-M PA assay. All data were converted to Stanford reference values. We used transabdominal ultrasound to determine prostate volume. PSAD was determined as the serum PSA/prostate volume ratio. The mean PSA values for BPH and prostate cancer were 6.42 +/- 1.80 and 7.80 +/- 2.15 ng/ml (p = 0.0116), respectively, and prostate volume was 33.4 +/- 14.1 ml and 17.1 +/- 8.2 ml, respectively (p < 0.0001). The mean PSAD for prostate cancer was 0.572 +/- 0.363 while that for BPH was 0.218 +/- 0.085 (p = 0.0001). Cut-off values with sensitivity > 90% were 0.218 for PSAD and 30 ml for prostate volume. At these cut-off values, specificity reached 56% for each marker. In discriminating prostate cancer from BPH in the gray zone of PSA, PSAD demonstrated better performance than PSA. PMID:10466060

  5. [Occult cancer in patients with symptomatic benign prostatic hyperplasia].

    PubMed

    Rodríguez Duarte, C; Aguillón, J; Rodríguez, H

    1991-05-01

    The results of a prospective study undertaken in 29 patients with symptomatic benign prostatic hyperplasia (BPH) are presented. Transrectal ultrasound, ultrasound-guided biopsy and prostate specific antigen (PSA) were utilized in the search for hidden cancer of the prostate. However, no cancer was detected in any patient. Very high values of PSA were found, particularly in patients with an indwelling catheter. Transrectal ultrasound yielded no false negatives and no complications were observed. PMID:1712190

  6. A Perspective of Immunotherapy for Prostate Cancer.

    PubMed

    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

  7. 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

  8. Proton-beam therapy for prostate cancer.

    PubMed

    Kagan, A Robert; Schulz, Robert J

    2010-01-01

    The treatment options for prostate cancer include prostatectomy, external-beam irradiation, brachytherapy, cryosurgery, focused ultrasound, hormonal therapy, watchful waiting, and various combinations of these modalities. Because the prostate abuts the bladder and rectum, the dose distributions of external-beam irradiations and the accuracy of their placement play crucial roles in the probability of tumor cure and the incidence of posttreatment complications. Principal among the newer radiation technologies is proton-beam therapy (PBT), whose dose distributions make it possible to deliver higher tumor doses and smaller doses to surrounding normal tissues than from x-ray systems. However, as the 10-year cause-specific survival for early-stage disease treated by radiation therapy now exceeds 90%, and with severe late toxicities in the range of 2% to 3%, randomized clinical trials provide the only means to demonstrate improved outcomes from PBT. Short of the data provided by such trials, the efficacy of PBT can be gleaned only from reports in the clinical literature, and, to date, these reports are equivocal. In view of the current health care crisis and the higher costs of PBT for prostate cancer, it is reasonable to assess the viability of this in-vogue but not-so-new technology. PMID:20890135

  9. Analysis of Prostate Deformation during a Course of Radiation Therapy for Prostate Cancer

    PubMed Central

    Nakazawa, Takuya; Tateoka, Kunihiko; Saito, Yuichi; Abe, Tadanori; Yano, Masaki; Yaegashi, Yuji; Narimatsu, Hirokazu; Fujimoto, Kazunori; Nakata, Akihiro; Nakata, Kensei; Someya, Masanori; Hori, Masakazu; Hareyama, Masato; Sakata, Koichi

    2015-01-01

    Purpose Accurate analysis of the correlation between deformation of the prostate and displacement of its center of gravity (CoG) is important for efficient radiation therapy for prostate cancer. In this study, we addressed this problem by introducing a new analysis approach. Method A planning computed tomography (CT) scan and 7 repeat cone-beam CT scans during the course of treatment were obtained for 19 prostate cancer patients who underwent three-dimensional conformal radiation therapy. A single observer contoured the prostate gland only. To evaluate the local deformation of the prostate, it was divided into 12 manually defined segments. Prostate deformation was calculated using in-house developed software. The correlation between the displacement of the CoG and the local deformation of the prostate was evaluated using multiple regression analysis. Results The mean value and standard deviation (SD) of the prostate deformation were 0.6 mm and 1.7 mm, respectively. For the majority of the patients, the local SD of the deformation was slightly lager in the superior and inferior segments. Multiple regression analysis revealed that the anterior-posterior displacement of the CoG of the prostate had a highly significant correlation with the deformations in the middle-anterior (p < 0.01) and middle-posterior (p < 0.01) segments of the prostate surface (R2 = 0.84). However, there was no significant correlation between the displacement of the CoG and the deformation of the prostate surface in other segments. Conclusion Anterior-posterior displacement of the CoG of the prostate is highly correlated with deformation in its middle-anterior and posterior segments. In the radiation therapy for prostate cancer, it is necessary to optimize the internal margin for every position of the prostate measured using image-guided radiation therapy. PMID:26120840

  10. [Clinical significance of prostate specific antigen and gamma-seminoprotein ratio for diagnosing prostate cancer].

    PubMed

    Akino, H; Suzuki, Y; Okada, K

    1998-08-01

    It has been reported that prostate specific antigen and gamma-seminoprotein ratio (PSA/gamma-Sm ratio) is an useful means for distinguishing benign prostatic hyperplasia and prostate cancer if serum PSA is measured by Eiken-PSA method. We studied the clinical significance of PSA/gamma-Sm ratio when using Markit-M-PSA method. PSA/gamma-Sm ratio had no superiority over PSA alone for detecting prostate cancer. The present results suggest that the clinical significance of PSA/gamma-Sm ratio can be varied by various PSA-assay kits. PMID:9750496

  11. 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…

  12. Prostate cancer education in the Washington, DC, area.

    PubMed Central

    Warrick, Cynthia; Wutoh, Anthony K.; Corria-McDow, Zakia; Emekalam, Anthony

    2002-01-01

    Pharmacists are key members of the healthcare team, especially in minority and urban communities. This study was developed to assess pharmacists' ability and willingness to counsel the public on prostate cancer in the community pharmacy setting. A mail survey was sent to all 192 community pharmacies in Washington, DC, and Prince George's County, Maryland. A total of 90 pharmacists responded to the questionnaire, providing a 46.9% response rate. One third of the pharmacists indicated a willingness to participate in a prostate cancer training program. Perceived benefits and perceived barriers were each measured through five questionnaire items using Likert-style statements with responses ranging from "strongly agree" to "strongly disagree." The most significant predictor of perceived benefits of providing prostate cancer information was gender; male pharmacists perceived greater benefits for providing prostate cancer information than female pharmacists. Similarly, black pharmacists perceived greater benefits of providing prostate cancer information to their patients than non-black pharmacists. Also, pharmacists in stores that offered disease state management programs had a significantly lower perceived benefit of providing prostate cancer information. These findings indicate that gender and race may play a role in health promotion in health disparities. There were no significant barriers to providing prostate cancer information. Thus, many pharmacists are willing to participate in health education on prostate cancer. PMID:12442999

  13. Defining the threshold for significant versus insignificant prostate cancer.

    PubMed

    Van der Kwast, Theo H; Roobol, Monique J

    2013-08-01

    Autopsy studies have shown the presence of a large reservoir of latent prostate cancers in adult men. Serum PSA testing of asymptomatic men leads to the detection of a proportion of these latent prostate cancers. The unequivocal demonstration of a substantial (30-50%) risk of overdiagnosis by the two largest randomized population-based screening trials has led to a growing awareness of this unwanted effect. Unsurprisingly, active surveillance is now becoming the favoured strategy for deferring active treatment in men diagnosed with low-risk prostate cancer and reducing their risk of overtreatment. Almost all eligibility criteria for active surveillance refer to a strict pathological definition of insignificant prostate cancer, based on two landmark studies published about 20 years ago. However, current epidemiological data suggest that this original pathological definition of insignificant prostate cancer is too restrictive. In addition, the International Society of Urological Pathology (ISUP) 2005 modification to the Gleason grading system might have resulted in a marked upgrading of biopsy-diagnosed prostate cancers, reducing the number of men eligible for active surveillance. An updated definition of insignificant prostate cancer should reflect the optimal trade-off between reducing the risk of underestimating a significant prostate cancer and including as many men as possible in active surveillance programmes. PMID:23712205

  14. Hormone Therapy for Prostate Cancer Tied to Depression

    MedlinePlus

    ... html Hormone Therapy for Prostate Cancer Tied to Depression Study found a 23 percent increased risk compared ... cancer may be at increased risk of developing depression, a new, large study suggests. The findings are ...

  15. Microwave Treatment of Prostate Cancer and Hyperplasia

    NASA Technical Reports Server (NTRS)

    Arndt, G. Dickey; Ngo, Phong; Carl, J. R.; Raffoul, George

    2005-01-01

    Microwave ablation in the form of microwave energy applied to a heart muscle by a coaxial catheter inserted in a vein in the groin area can be used to heat and kill diseased heart cells. A microwave catheter has been developed to provide deep myocardial ablation to treat ventricular tachycardia by restoring appropriate electrical activity within the heart and eliminating irregular heartbeats. The resulting microwave catheter design, which is now being developed for commercial use in treating ventricular tachycardia, can be modified to treat prostate cancer and benign prostatic hyperplasia (BPH). Inasmuch as the occurrence of BPH is increasing currently 350,000 operations per year are performed in the United States alone to treat this condition this microwave catheter has significant commercial potential.

  16. 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

  17. General Information about Prostate Cancer

    MedlinePlus

    ... professional versions have detailed information written in technical language. The patient versions are written in easy-to-understand, nontechnical language. Both versions have cancer information that is accurate ...

  18. 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

  19. Is There a Future for Chemoprevention of Prostate Cancer?

    PubMed

    Bosland, Maarten C

    2016-08-01

    The outcome of the Selenium and Vitamin E Cancer Prevention Trial, demonstrating harm and no preventive activity of selenomethionine and α-tocopherol for prostate cancer, and the lack of approval by the FDA for the use of 5α-reductase inhibitors to prevent prostate cancer have cast doubt about the future of chemoprevention of prostate cancer. This article attempts to critically assess whether the notion that chemoprevention of prostate cancer has no future is warranted. Risk of prostate cancer is modifiable and chemoprevention of prostate cancer, particularly fatal/lethal cancer, is both needed and possible. However, the approach to prostate cancer-chemopreventive agent development has not followed a rational and systematic process. To make progress, the following steps are necessary: (i) identification of intermediate biomarkers predictive of fatal/lethal disease; (ii) development of a rational approach to identification of candidate agents, including high-throughput screening and generation of information on mechanism and biology of candidate agents and potential molecular targets; and (iii) systematic evaluation of the predictive value of preclinical models, phase II trials, and intermediate biomarkers for the outcome of phase III trials. New phase III trials should be based on adequate preclinical and phase II studies. Cancer Prev Res; 9(8); 642-7. ©2016 AACR. PMID:27099271

  20. Proteomics in diagnosis of prostate cancer.

    PubMed

    Davalieva, K; Polenakovic, M

    2015-01-01

    Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. The introduction of prostate specific antigen (PSA) has greatly increased the number of men diagnosed with PCa but at the same time, as a result of the low specificity, led to overdiagnosis, resulting to unnecessary biopsies and high medical cost treatments. The primary goal in PCa research today is to find a biomarker or biomarker set for clear and effecttive diagnosis of PCa as well as for distinction between aggressive and indolent cancers. Different proteomic technologies such as 2-D PAGE, 2-D DIGE, MALDI MS profiling, shotgun proteomics with label-based (ICAT, iTRAQ) and label-free (SWATH) quantification, MudPIT, CE-MS have been applied to the study of PCa in the past 15 years. Various biological samples, including tumor tissue, serum, plasma, urine, seminal plasma, prostatic secretions and prostatic-derived exosomes were analyzed with the aim of identifying diagnostic and prognostic biomarkers and developing a deeper understanding of the disease at the molecular level. This review is focused on the overall analysis of expression proteomics studies in the PCa field investigating all types of human samples in the search for diagnostics biomarkers. Emphasis is given on proteomics platforms used in biomarker discovery and characterization, explored sources for PCa biomarkers, proposed candidate biomarkers by comparative proteomics studies and the possible future clinical application of those candidate biomarkers in PCa screening and diagnosis. In addition, we review the specificity of the putative markers and existing challenges in the proteomics research of PCa. PMID:26076772

  1. Recent adverse trends in semen quality and testis cancer incidence among Finnish men

    PubMed Central

    Jørgensen, N; Vierula, M; Jacobsen, R; Pukkala, E; Perheentupa, A; Virtanen, H E; Skakkebæk, N E; Toppari, J

    2011-01-01

    Impaired semen quality and testicular cancer may be linked through a testicular dysgenesis syndrome of foetal origin. The incidence of testis cancer has been shown to increase among Finnish men, whereas there is no recent publication describing temporal trends in semen quality. Therefore, we carried out a prospective semen quality study and a registry study of testis cancer incidence among Finnish men to explore recent trends. A total of 858 men were investigated in the semen quality study during 1998–2006. Median sperm concentrations were 67 (95% CI 57–80) million/mL, 60 (51–71) and 48 (39–60) for birth cohorts 1979–81, 1982–83 and 1987; total sperm counts 227 (189–272) million, 202 (170–240) and 165 (132–207); total number of morphologically normal spermatozoa 18 (14–23) million, 15 (12–19) and 11 (8–15). Men aged 10–59 years at the time of diagnosis with testicular cancer during 1954–2008 were included in the registry study, which confirmed the increasing incidence of testicular cancer in recent cohorts. These simultaneous and rapidly occurring adverse trends suggest that the underlying causes are environmental and, as such, preventable. Our findings necessitate not only further surveillance of male reproductive health but also research to detect and remove the underlying factors. PMID:21366607

  2. 5alpha-reductase inhibitors in benign prostatic hyperplasia and prostate cancer risk reduction.

    PubMed

    Rittmaster, Roger S

    2008-04-01

    Androgens play an essential role in prostatic development and function, but are also involved in prostate disease pathogenesis. The primary prostatic androgen, dihydrotestosterone (DHT), is synthesized from testosterone by 5alpha-reductase types 1 and 2. Inhibition of the 5alpha-reductase isoenzymes therefore has potential therapeutic benefit in prostate disease. The two currently approved 5alpha-reductase inhibitors (5ARIs), finasteride and dutasteride, have demonstrated long-term efficacy and safety in the treatment of benign prostatic hyperplasia. Finasteride, a type-2 5ARI, has also been studied for its ability to reduce the incidence of biopsy-detectable prostate cancer in the Prostate Cancer Prevention Trial. Treatment with dutasteride, a dual 5ARI, has been shown to result in a greater degree and consistency of DHT suppression compared with finasteride. Two large-scale studies of dutasteride are currently investigating the role of near-maximal DHT suppression in the settings of prostate cancer risk reduction and expectant management of localized prostate cancer. PMID:18471794

  3. Clinical variability and molecular heterogeneity in prostate cancer.

    PubMed

    Shoag, Jonathan; Barbieri, Christopher E

    2016-01-01

    Prostate cancer is a clinically heterogeneous disease, with some men having indolent disease that can safely be observed, while others have aggressive, lethal disease. Over the past decade, researchers have begun to unravel some of the genomic heterogeneity that contributes to these varying clinical phenotypes. Distinct molecular sub-classes of prostate cancer have been identified, and the uniqueness of these sub-classes has been leveraged to predict clinical outcomes, design novel biomarkers for prostate cancer diagnosis, and develop novel therapeutics. Recent work has also elucidated the temporal and spatial heterogeneity of prostate cancer, helping us understand disease pathogenesis, response to therapy, and progression. New genomic techniques have provided us with a window into the remarkable clinical and genomic heterogeneity of prostate cancer, and this new perspective will increasingly impact patient care. PMID:27080479

  4. Clinical variability and molecular heterogeneity in prostate cancer

    PubMed Central

    Shoag, Jonathan; Barbieri, Christopher E

    2016-01-01

    Prostate cancer is a clinically heterogeneous disease, with some men having indolent disease that can safely be observed, while others have aggressive, lethal disease. Over the past decade, researchers have begun to unravel some of the genomic heterogeneity that contributes to these varying clinical phenotypes. Distinct molecular sub-classes of prostate cancer have been identified, and the uniqueness of these sub-classes has been leveraged to predict clinical outcomes, design novel biomarkers for prostate cancer diagnosis, and develop novel therapeutics. Recent work has also elucidated the temporal and spatial heterogeneity of prostate cancer, helping us understand disease pathogenesis, response to therapy, and progression. New genomic techniques have provided us with a window into the remarkable clinical and genomic heterogeneity of prostate cancer, and this new perspective will increasingly impact patient care. PMID:27080479

  5. Active surveillance for prostate cancer: patient selection and management

    PubMed Central

    Klotz, L.

    2010-01-01

    Screening for prostate cancer using prostate-specific antigen (psa) has been appealing. However, the significant associated decline in prostate cancer mortality comes at the cost of a very high rate of diagnosis, and many patients with indolent, non-life-threatening cancer are exposed to the risk of significant side effects from radical treatment. Most men with favourable-risk prostate cancer are not destined to die of their disease, even in the absence of treatment. The challenge is to identify the subset that harbour more aggressive disease early enough that curative therapy is still a possibility, thereby allowing the others to enjoy improved quality of life, free from the side effects of treatment. This article reviews current research into active surveillance in favourable-risk disease and some of the issues that arise when prostate cancer is monitored rather than being treated immediately. PMID:20882126

  6. Targeting PARP in Prostate Cancer: Novelty, Pitfalls, and Promise.

    PubMed

    Palmbos, Phillip L; Hussain, Maha H

    2016-05-01

    Metastatic prostate cancer remains a highly lethal disease with no curative therapeutic options. A significant subset of patients with prostate cancer harbor either germline or somatic mutations in DNA repair enzyme genes such as BRCA1, BRCA2, or ATM. Emerging data suggest that drugs that target poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) enzymes may represent a novel and effective means of treating tumors with these DNA repair defects, including prostate cancers. Here we will review the molecular mechanism of action of PARP inhibitors and discuss how they target tumor cells with faulty DNA repair functions and transcriptional controls. We will review emerging data for the utility of PARP inhibition in the management of metastatic prostate cancer. Finally, we will place PARP inhibitors within the framework of precision medicine-based care of patients with prostate cancer. PMID:27188668

  7. A microRNA code for prostate cancer metastasis

    PubMed Central

    Bonci, D; Coppola, V; Patrizii, M; Addario, A; Cannistraci, A; Francescangeli, F; Pecci, R; Muto, G; Collura, D; Bedini, R; Zeuner, A; Valtieri, M; Sentinelli, S; Benassi, M S; Gallucci, M; Carlini, P; Piccolo, S; De Maria, R

    2016-01-01

    Although the development of bone metastasis is a major detrimental event in prostate cancer, the molecular mechanisms responsible for bone homing and destruction remain largely unknown. Here we show that loss of miR-15 and miR-16 in cooperation with increased miR-21 expression promote prostate cancer spreading and bone lesions. This combination of microRNA endows bone-metastatic potential to prostate cancer cells. Concomitant loss of miR-15/miR-16 and gain of miR-21 aberrantly activate TGF-β and Hedgehog signaling, that mediate local invasion, distant bone marrow colonization and osteolysis by prostate cancer cells. These findings establish a new molecular circuitry for prostate cancer metastasis that was validated in patients' cohorts. Our data indicate a network of biomarkers and druggable pathways to improve patient treatment. PMID:26073083

  8. 3 CFR 8408 - Proclamation 8408 of August 31, 2009. National Prostate Cancer Awareness Month, 2009

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Prostate Cancer Awareness Month, 2009 8408 Proclamation 8408 Presidential Documents Proclamations Proclamation 8408 of August 31, 2009 Proc. 8408 National Prostate Cancer Awareness Month, 2009By the President... fight against prostate cancer. Over the last decade, prostate cancer mortality rates have...

  9. Does length of prostate biopsy cores have an impact on diagnosis of prostate cancer?

    PubMed Central

    Ergün, Müslüm; İslamoğlu, Ekrem; Yalçınkaya, Soner; Tokgöz, Hüsnü; Savaş, Murat

    2016-01-01

    Objective To investigate whether core length is a significant biopsy parameter in the detection of prostate cancer. Material and methods We retrospectively analyzed pathology reports of the specimens of 188 patients diagnosed with prostate cancer who had undergone initial transrectal ultrasound (TRUS) guided prostate biopsy, and compared biopsy core lengths of the patients with, and without prostate cancer. The biopsy specimens of prostate cancer patients were divided into 3 groups according to core length, and the data obtained were compared (Group 1; total core length <10 mm, Group 2; total core length 10 mm–19 mm, and Group 3; total core length >20 mm). Biopsy core lengths of the patients diagnosed as prostate cancer, and benign prostatic hyperplasia were compared, and a certain cut-off value for core length with optimal diagnostic sensitivity and specificity for prostate cancer was calculated. Results Mean age, PSA and total length of cores were 65.08±7.41 years, 9.82±6.34 ng/mL and 11.2±0.2 mm, respectively. Assessment of biopsy core lengths showed that cores with cancer (n=993, median length 12.5 mm) were significantly longer than benign cores (n=1185, median length=11.3 mm) (p<0.001). Core length analysis yielded 12 mm cores have an optimal sensitivity (41.9%) and specificity (62%) for detection of cancer (odds ratio: 1.08). Conclusion Biopsy core length is one of the most important parameter that determines the quality of biopsy and detection of prostate cancer. A median sample length of 12 mm is ideal lower limit for cancer detection, and biopsy procedures which yield shorter biopsy cores should be repeated.

  10. [Postoperative radiotherapy of prostate cancer].

    PubMed

    Guérif, S; Latorzeff, I; Lagrange, J-L; Hennequin, C; Supiot, S; Garcia, A; François, P; Soulié, M; Richaud, P; Salomon, L

    2014-10-01

    Between 10 and 40% of patients who have undergone a radical prostatectomy may have a biologic recurrence. Local or distant failure represents the possible patterns of relapse. Patients at high-risk for local relapse have extraprostatic disease, positive surgical margins or seminal vesicles infiltration or high Gleason score at pathology. Three phase-III randomized clinical trials have shown that, for these patients, adjuvant irradiation reduces the risk of tumoral progression without higher toxicity. Salvage radiotherapy for late relapse allows a disease control in 60-70% of the cases. Several research in order to improve the therapeutic ratio of the radiotherapy after prostatectomy are evaluate in the French Groupe d'Étude des Tumeurs Urogénitales (Gétug) and of the French association of urology (Afu). The Gétug-Afu 17 trial will provide answers to the question of the optimal moment for postoperative radiotherapy for pT3-4 R1 pN0 Nx patients, with the objective of comparing an immediate treatment to a differed early treatment initiated at biological recurrence. The Gétug-Afu 22 questions the place of a short hormonetherapy combined with image-guided, intensity-modulated radiotherapy (IMRT) in adjuvant situation for a detectable prostate specific antigen (PSA). The implementation of a multicenter quality control within the Gétug-Afu in order to harmonize a modern postoperative radiotherapy will allow the development of a dose escalation IMRT after surgery. PMID:25195116

  11. 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

  12. Progress of molecular targeted therapies for prostate cancers

    PubMed Central

    Fu, Weihua; Madan, Elena; Yee, Marla; Zhang, Hongtao

    2011-01-01

    Prostate cancer remains the most commonly diagnosed malignancy and the second leading cause of cancer-related deaths in men in the United States. The current standard of care consists of prostatectomy and radiation therapy, which may often be supplemented with hormonal therapies. Recurrence is common, and many develop metastatic prostate cancer for which chemotherapy is only moderately effective. It is clear that novel therapies are needed for the treatment of the malignant forms of prostate cancer that recur after initial therapies, such as hormone refractory (HRPC) or castration resistant prostate cancer (CRPC). With advances in understanding of the molecular mechanisms of cancer, we have witnessed unprecedented progress in developing new forms of targeted therapy. Several targeted therapeutic agents have been developed and clinically used for the treatment of solid tumors such as breast cancer, non-small cell lung cancer, and renal cancer. Some of these reagents modulate growth factors and/or their receptors, which are abundant in cancer cells. Other reagents target the downstream signal transduction, survival pathways, and angiogenesis pathways that are abnormally activated in transformed cells or metastatic tumors. We will review current developments in this field, focusing specifically on treatments that can be applied to prostate cancers. Finally we will describe aspects of the future direction of the field with respect to discovering biomarkers to aid in identifying responsive prostate cancer patients. PMID:22146293

  13. Marked heterogeneity of ERG expression in large primary prostate cancers.

    PubMed

    Minner, Sarah; Gärtner, Michael; Freudenthaler, Fabian; Bauer, Melanie; Kluth, Martina; Salomon, Georg; Heinzer, Hans; Graefen, Markus; Bokemeyer, Carsten; Simon, Ronald; Sauter, Guido; Schlomm, Thorsten; Wilczak, Waldemar

    2013-01-01

    Approximately 50% of prostate cancers are characterized by TMPRSS2 (transmembrane protease serine 2)-ERG (avian v-ets erythroblastosis virus E26 oncogene homolog) gene fusions resulting in an androgen-regulated overexpression of the transcription factor ERG. Some studies have suggested prognostic or predictive relevance of ERG status in prostate cancer. Such concepts could be impaired by extensive ERG heterogeneity in analyzed tumors. The aim of this study was to analyze the extent of heterogeneity for TMPRSS2-ERG fusion in prostate cancer. To enable large-scale studies on the extent of heterogeneity of biomarkers in prostate cancer, a heterogeneity tissue microarray containing samples from 10 different tumor blocks of 190 large prostate cancers selected from a consecutive series of 480 radical prostatectomies was developed. ERG expression was analyzed by immunohistochemistry. Positive ERG immunostaining was found in arrayed cancer-containing samples from 103 of the 178 analyzable patients (58%). ERG immunostaining was homogeneously positive in 29 prostate cancers (16%), whereas heterogeneous ERG positivity was seen in 74 cancers (42%). ERG heterogeneity was within one tumor focus (intrafocal heterogeneity) in 69 cases (93% of heterogeneous cases) and between different tumor foci (interfocal heterogeneity) in 5 cases (7%). Marked intrafocal heterogeneity challenges the concept of TMPRSS2-ERG fusion always representing an early step in prostate cancer development. Marked heterogeneity also compromises the concept of analyzing ERG status for treatment decisions in diagnostic needle core biopsies. PMID:22899295

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

    PubMed

    Rizos, Ch; Papassava, M; Golias, Ch; Charalabopoulos, K

    2010-07-01

    Prostate cancer has become a major public health problem worldwide although the etiology of prostate cancer remains largely unknown. Dietary factors, dietary supplements, and physical activity might be important in the prevention of the disease. In the majority of studies published, it was observed that high consumption of meat, alcohol and dairy products has been linked to a greater risk. Specifically, alcohol use, and particularly heavy use, may cause cancers of liver, esophagus, larynx, pharynx and oral cavity, with risks for the aero-digestive cancers. Moderate use among women has been related with increases in breast cancer. Alcohol consumption is a modifiable lifestyle factor that may affect prostate cancer risk. Alcohol alters the hormonal environment and in parallel, containing chemical substances such as flavonoids (red wine), may alter tumor cell growth. In this mini review, the relation between alcohol consumption and prostate cancer risk is analyzed. PMID:20693964

  15. Analysis of Urinary Prostate-Specific Antigen Glycoforms in Samples of Prostate Cancer and Benign Prostate Hyperplasia

    PubMed Central

    Hsiao, Chun-Jen; Tzai, Tzong-Shin; Chen, Chein-Hung; Yang, Wen-Horng; Chen, Chung-Hsuan

    2016-01-01

    Glycans of prostate-specific antigen (PSA) in prostate cancer were found to be different from that in benign disease. It is difficult to analyze heterogeneous PSA glycoforms in each individual specimen because of low protein abundance and the limitation of detection sensitivity. We developed a method for prostate cancer diagnosis based on PSA glycoforms. Specific glycoforms were screened in each clinical sample based on liquid chromatography-tandem mass spectrometry with ion accumulation. To look for potential biomarkers, normalized abundance of each glycoform in benign prostate hyperplasia (BPH) and in prostate cancer was evaluated. The PSA glycoform, Hex5HexNAc4NeuAc1dHex1, and monosialylated, sialylated, and unfucosylated glycoforms differed significantly between the prostate cancer and BPH samples. The detection sensitivity (87.5%) and specificity (60%) for prostate cancer identification are higher than those of the serum PSA marker. As low as 100 amol PSA could be detected with the ion accumulation method which has not been reported before. The improved detection specificity can help reduce unnecessary examinations. PMID:27065039

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

    PubMed Central

    Simoneau, Anne R

    2006-01-01

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

  17. 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. PMID:25557753

  18. Managing the low-socioeconomic-status prostate cancer patient.

    PubMed

    Rayford, Walter

    2006-04-01

    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

  19. 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

  20. Metastatic prostate cancer initially presenting as chylothorax: A case report

    PubMed Central

    YANG, YU-JIN; SEO, MINJUNG; JEON, HEE-JEONG; NOH, JIN-HEE; PARK, SEOL HOON; CHOI, YUNSUK; JO, JAE-CHEOL; BAEK, JIN HO; KOH, SU-JIN; KIM, HAWK; MIN, YOUNG JOO

    2016-01-01

    Chylothorax is caused by disruption or obstruction of the thoracic duct, which results in leakage of chyle in the pleural space. The most common etiologies are malignancy and trauma. Among the causative malignancies, lymphoma is the most common, followed by primary lung cancer, mediastinal tumors, and other metastatic malignancies. Conversely, prostate cancer has rarely been reported as the cause of chylothorax. We herein report a case of metastatic prostate cancer initially presenting as chylothorax, with disappearance of the pleural effusion after the initiation of androgen deprivation therapy. Moreover, we also discuss the various rare manifestations of metastatic prostate cancer, including chylothorax. PMID:27313861

  1. Advances in genetics: widening our understanding of prostate cancer

    PubMed Central

    Pine, Angela C.; Fioretti, Flavia F.; Brooke, Greg N.; Bevan, Charlotte L.

    2016-01-01

    Prostate cancer is a leading cause of cancer-related death in Western men. Our understanding of the genetic alterations associated with disease predisposition, development, progression, and therapy response is rapidly improving, at least in part, owing to the development of next-generation sequencing technologies. Large advances have been made in our understanding of the genetics of prostate cancer through the application of whole-exome sequencing, and this review summarises recent advances in this field and discusses how exome sequencing could be used clinically to promote personalised medicine for prostate cancer patients. PMID:27408704

  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. Circumcision and the risk of prostate cancer

    PubMed Central

    Wright, Jonathan L; Lin, Daniel W; Stanford, Janet L

    2011-01-01

    Background Several lines of evidence support a role for infectious agents in the development of prostate cancer (PCa). In particular, sexually transmitted infections (STIs) have been implicated in PCa etiology, and studies have found that the risk of acquiring a STI can be reduced with circumcision. Therefore, circumcision may reduce PCa risk. Methods Participant data collected as part of two population-based case-control studies of PCa were analyzed. Self-reported circumcision status, age at circumcision and age at first sexual intercourse were recorded along with a history of STIs or prostatitis. Multivariate logistic regression was used to estimate the relative risk of PCa by circumcision status. Results Data from 1,754 cases and 1,645 controls were available. Circumcision before first sexual intercourse was associated with a 15% reduction in risk of PCa compared to uncircumcised men (95% CI 0.73 – 0.99). This risk reduction was observed for cases with both less aggressive (OR 0.88, 95% CI 0.74 – 1.04) and more aggressive (OR 0.82, 95% CI 0.66 – 1.00) PCa features. Conclusions Circumcision before first sexual intercourse is associated with a reduction in the relative risk of PCa in this study population. These findings are consistent with research supporting the infectious/inflammation pathway in prostate carcinogenesis. PMID:22411189

  4. Loss of JUNB/AP-1 promotes invasive prostate cancer

    PubMed Central

    Thomsen, M K; Bakiri, L; Hasenfuss, S C; Wu, H; Morente, M; Wagner, E F

    2015-01-01

    Prostate cancer is a frequent cause of male death in the Western world. Relatively few genetic alterations have been identified, likely owing to disease heterogeneity. Here, we show that the transcription factor JUNB/AP-1 limits prostate cancer progression. JUNB expression is increased in low-grade prostate cancer compared with normal human prostate, but downregulated in high-grade samples and further decreased in all metastatic samples. To model the hypothesis that this downregulation is functionally significant, we genetically inactivated Junb in the prostate epithelium of mice. When combined with Pten (phosphatase and tensin homologue) loss, double-mutant mice were prone to invasive cancer development. Importantly, invasive tumours also developed when Junb and Pten were inactivated in a small cell population of the adult anterior prostate by topical Cre recombinase delivery. The resulting tumours displayed strong histological similarity with human prostate cancer. Loss of JunB expression led to increased proliferation and decreased senescence, likely owing to decreased p16Ink4a and p21CIP1 in epithelial cells. Furthermore, the tumour stroma was altered with increased osteopontin and S100 calcium-binding protein A8/9 expression, which correlated with poor prognoses in patients. These data demonstrate that JUNB/AP-1 cooperates with PTEN signalling as barriers to invasive prostate cancer, whose concomitant genetic or epigenetic suppression induce malignant progression. PMID:25526087

  5. Loss of JUNB/AP-1 promotes invasive prostate cancer.

    PubMed

    Thomsen, M K; Bakiri, L; Hasenfuss, S C; Wu, H; Morente, M; Wagner, E F

    2015-04-01

    Prostate cancer is a frequent cause of male death in the Western world. Relatively few genetic alterations have been identified, likely owing to disease heterogeneity. Here, we show that the transcription factor JUNB/AP-1 limits prostate cancer progression. JUNB expression is increased in low-grade prostate cancer compared with normal human prostate, but downregulated in high-grade samples and further decreased in all metastatic samples. To model the hypothesis that this downregulation is functionally significant, we genetically inactivated Junb in the prostate epithelium of mice. When combined with Pten (phosphatase and tensin homologue) loss, double-mutant mice were prone to invasive cancer development. Importantly, invasive tumours also developed when Junb and Pten were inactivated in a small cell population of the adult anterior prostate by topical Cre recombinase delivery. The resulting tumours displayed strong histological similarity with human prostate cancer. Loss of JunB expression led to increased proliferation and decreased senescence, likely owing to decreased p16(Ink4a) and p21(CIP1) in epithelial cells. Furthermore, the tumour stroma was altered with increased osteopontin and S100 calcium-binding protein A8/9 expression, which correlated with poor prognoses in patients. These data demonstrate that JUNB/AP-1 cooperates with PTEN signalling as barriers to invasive prostate cancer, whose concomitant genetic or epigenetic suppression induce malignant progression. PMID:25526087

  6. The Prostate Health Index: a new test for the detection of prostate cancer

    PubMed Central

    Loeb, Stacy

    2014-01-01

    A major focus in urologic research is the identification of new biomarkers with improved specificity for clinically-significant prostate cancer. A promising new test based on prostate-specific antigen (PSA) is called the Prostate Health Index (PHI), which has recently been approved in the United States, Europe and Australia. PHI is a mathematical formula that combines total PSA, free PSA and [-2] proPSA. Numerous international studies have consistently shown that PHI outperforms its individual components for the prediction of overall and high-grade prostate cancer on biopsy. PHI also predicts the likelihood of progression during active surveillance, providing another noninvasive modality to potentially select and monitor this patient population. This article reviews the evidence on this new blood test with significant promise for both prostate cancer screening and treatment decision-making. PMID:24688603

  7. The Eastland Prostate Cancer Survey: instrument development and psychometric testing.

    PubMed

    Eastland, Taryn Y; Dancy, Barbara L

    2013-03-01

    African-American (AA) women could be instrumental in communicating positive prostate screening behavior to the significant males in their lives. However, little is known about AA women's prostate cancer attitudes, perceived behavioral control, subjective norms, intentions, behaviors, and knowledge regarding prostate cancer screening. This study describes the development and psychometric testing of the Eastland Prostate Cancer Survey (EPCS). A nonexperimental, correlational study with 200 AA women was used to test the psychometric properties of the six-subscale EPCS with 66 items. Construct validity, internal consistency, and test-retest reliability for the EPCS were acceptable and resulted in an eight-subscale EPCS with 56 items. Cronbach's alphas for the subscales ranged from 0.69 to 0.92. The EPCS is a culturally sensitive, gender-relevant instrument that could be used by community health providers to develop community health programs aimed at engaging AA women in the promotion of prostate cancer screening for AA men. PMID:23288607

  8. Steroid hormone synthetic pathways in prostate cancer.

    PubMed

    Mostaghel, Elahe A

    2013-09-01

    While androgen deprivation therapy (ADT) remains the primary treatment for metastatic prostate cancer (PCa) since the seminal recognition of the disease as androgen-dependent by Huggins and Hodges in 1941, therapy is uniformly marked by progression to castration-resistant prostate cancer (CRPC) over a period of about 18 months, with an ensuing median survival of 1 to 2 years. Importantly, castration does not eliminate androgens from the prostate tumor microenvironment. Castration resistant tumors are characterized by elevated tumor androgens that are well within the range capable of activating the AR and AR-mediated gene expression, and by steroid enzyme alterations which may potentiate de novo androgen synthesis or utilization of circulating adrenal androgens. The dependence of CRPC on intratumoral androgen metabolism has been modeled in vitro and in vivo, and residual intratumoral androgens are implicated in nearly every mechanism by which AR-mediated signaling promotes castration-resistant disease. These observations suggest that tissue based alterations in steroid metabolism contribute to the development of CRPC and underscore these metabolic pathways as critical targets of therapy. Herein, we review the accumulated body of evidence which strongly supports intracrine (tumoral) androgen synthesis as an important mechanism underlying PCa progression. We first discuss the presence and significance of residual prostate tumor androgens in the progression of CRPC. We review the classical and non-classical pathways of androgen metabolism, and how dysregulated expression of these enzymes is likely to potentiate tumor androgen production in the progression to CRPC. Next we review the in vitro and in vivo data in human tumors, xenografts, and cell line models which demonstrate the capacity of prostate tumors to utilize cholesterol and adrenal androgens in the production of testosterone (T) and dihydrotestosterone (DHT), and briefly review the potential role of exogenous

  9. SU-E-J-95: Predicting Treatment Outcomes for Prostate Cancer: Irradiation Responses of Prostate Cancer Stem Cells

    SciTech Connect

    Wang, K

    2014-06-01

    Purpose: Most prostate cancers are slow-growing diseases but normally require much higher doses (80Gy) with conventional fractionation radiotherapy, comparing to other more aggressive cancers. This study is to disclose the radiobiological basis of this discrepancy by proposing the concept of prostate cancer stem cells (CSCs) and examining their specific irradiation responses. Methods: There are overwhelming evidences that CSC may keep their stemness, e.g. the competency of cell differentiation, in hypoxic microenvironments and hence become radiation resistive, though the probability is tiny for aggressiveness cancers. Tumor hypoxia used to be considered as an independent reason for poor treatment outcomes, and recent evidences showed that even prostate cancers were also hypoxic though they are very slow-growing. In addition, to achieve comparable outcomes to other much more aggressive cancers, much higher doses (rather than lower doses) are always needed for prostate cancers, regardless of its non-aggressiveness. All these abnormal facts can only be possibly interpreted by the irradiation responses characteristics of prostate CSCs. Results: Both normal cancer cells (NCCs) and CSCs exiting in tumors, in which NCCs are mainly for symptoms whereas killing all CSCs achieves disease-free. Since prostate cancers are slow-growing, the hypoxia in prostate cancers cannot possibly from NCCs, thus it is caused by hypoxic CSCs. However, single hypoxic cell cannot be imaged due to limitation of imaging techniques, unless a large group of hypoxic cells exist together, thus most of CSCs in prostate cancers are virtually hypoxic, i.e. not in working mode because CSCs in proliferating mode have to be normoxic, and this explains why prostate cancers are unaggressive. Conclusion: The fractional dose in conventional radiotherapy (∼2Gy) could only kill NCCs and CSCs in proliferating modes, whereas most CSCs survived fractional treatments since they were hypoxic, thus to eliminate all

  10. Screening Prostate-specific Antigen Concentration and Prostate Cancer Mortality: The Korean Heart Study

    PubMed Central

    Mok, Yejin; Kimm, Heejin; Shin, Sang Yop; Jee, Sun Ha; Platz, Elizabeth A.

    2015-01-01

    OBJECTIVE To evaluate the association between serum prostate-specific antigen (PSA) concentration from a screening test and prostate cancer mortality in an Asian population. METHODS We included 118,665 men in the Korean Heart Study, a large prospective cohort study of participants who voluntarily underwent private health examinations that included PSA-based prostate cancer screening. The baseline visit occurred between January 1994 and December 2004, and follow-up was through December 2011. Deaths from prostate cancer were ascertained from the underlying cause of death from a computerized search of death certificate data from the National Statistical Office in Korea. We used the Cox proportional hazards regression to estimate the association between serum PSA and risk of prostate cancer death adjusting the baseline age, cigarette smoking status, and body mass index. RESULTS During 1,381,901 person-years of follow-up, 6036 men died of any cause, and of these, 56 men died of prostate cancer. The multivariate-adjusted hazard ratio for prostate cancer death statistically significantly increased across PSA concentrations (P trend <.0001). The hazard ratio increased 7% per 1-ng/mL increase in PSA. The association between PSA concentration and death from prostate cancer was stronger in younger than in older men and in heavier than leaner men. CONCLUSION In conclusion, an increased screening PSA level is associated with an increased risk of prostate cancer death in Korean men. Our findings may have implications for the development of targeted PSA cutpoints for biopsy recommendation. PMID:25917733

  11. 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

  12. Therapeutic vaccines for prostate cancer: recent advances and future directions.

    PubMed

    Strauss, Julius; Madan, Ravi A

    2016-07-01

    In recent years, therapeutic cancer vaccines have emerged as a viable and promising treatment for prostate cancer. Beyond sipuleucel-T, phase III trials are evaluating multiple vaccine platforms in men with this disease. Growing data evaluating vaccine therapies suggests that these agents are more effective in patients with more indolent and possibly also earlier stages of disease. In addition, a wealth of preclinical data has shown that traditional prostate cancer treatments including anti androgens, cytotoxic and radiation therapies may provide immunologic synergy when given in combination with vaccine platforms. Building off this data, numerous clinical trials are evaluating therapeutic cancer vaccines in early stage prostate cancer and also in combination with traditional prostate cancer therapies. In addition, in order to optimize immune responses, ongoing trials are evaluating vaccines in combination with immune checkpoint inhibitors. Preliminary data from these trials have been promising and are offering an exciting glimpse at the future of immunotherapy for this disease. PMID:26889831

  13. 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

  14. Interleukin-6: a multifunctional targetable cytokine in human prostate cancer.

    PubMed

    Culig, Zoran; Puhr, Martin

    2012-09-01

    Several cytokines are involved in regulation of cellular events in prostate cancer. Interleukin-6 (IL-6) was frequently investigated in prostate cancer models because of its increased expression in cancer tissue at early stages of the disease. In patients with metastatic prostate cancer, it is well-known that IL-6 levels increase in serum. High levels of IL-6 were measured in the supernatants of cells which do not respond to androgenic stimulation. IL-6 expression in prostate cancer increases due to enhanced expression of transforming growth factor-beta, and members of the activating protein-1 complex, and loss of the retinoblastoma tumour suppressor. IL-6 activation of androgen receptor (AR) may contribute to progression of a subgroup of prostate cancers. Results obtained with two prostate cancer cell lines, LNCaP and MDA PCa 2b, indicate that IL-6 activation of AR may cause either stimulatory or inhibitory responses on proliferation. Interestingly, prolonged treatment with IL-6 led to establishment of an IL-6 autocrine loop, suppressed signal transducer and activator of transcription (STAT)3 activation, and increased mitogen-activated protein kinase phosphorylation. In several cell lines IL-6 acts as a survival molecule through activation of the signalling pathway of phosphotidylinositol 3-kinase. Expression of suppressors of cytokine signalling (SOCS) has been studied in prostate cancer. SOCS-3 prevents phosphorylation of STAT3 and is an important anti-apoptotic factor in AR-negative prostate cancer cells. Experimental therapy against IL-6 in prostate cancer is based on the use of the monoclonal antibody siltuximab which may be used for personalised therapy coming in the future. PMID:21664423

  15. The mutational landscape of lethal castration-resistant prostate cancer.

    PubMed

    Grasso, Catherine S; Wu, Yi-Mi; Robinson, Dan R; Cao, Xuhong; Dhanasekaran, Saravana M; Khan, Amjad P; Quist, Michael J; Jing, Xiaojun; Lonigro, Robert J; Brenner, J Chad; Asangani, Irfan A; Ateeq, Bushra; Chun, Sang Y; Siddiqui, Javed; Sam, Lee; Anstett, Matt; Mehra, Rohit; Prensner, John R; Palanisamy, Nallasivam; Ryslik, Gregory A; Vandin, Fabio; Raphael, Benjamin J; Kunju, Lakshmi P; Rhodes, Daniel R; Pienta, Kenneth J; Chinnaiyan, Arul M; Tomlins, Scott A

    2012-07-12

    Characterization of the prostate cancer transcriptome and genome has identified chromosomal rearrangements and copy number gains and losses, including ETS gene family fusions, PTEN loss and androgen receptor (AR) amplification, which drive prostate cancer development and progression to lethal, metastatic castration-resistant prostate cancer (CRPC). However, less is known about the role of mutations. Here we sequenced the exomes of 50 lethal, heavily pre-treated metastatic CRPCs obtained at rapid autopsy (including three different foci from the same patient) and 11 treatment-naive, high-grade localized prostate cancers. We identified low overall mutation rates even in heavily treated CRPCs (2.00 per megabase) and confirmed the monoclonal origin of lethal CRPC. Integrating exome copy number analysis identified disruptions of CHD1 that define a subtype of ETS gene family fusion-negative prostate cancer. Similarly, we demonstrate that ETS2, which is deleted in approximately one-third of CRPCs (commonly through TMPRSS2:ERG fusions), is also deregulated through mutation. Furthermore, we identified recurrent mutations in multiple chromatin- and histone-modifying genes, including MLL2 (mutated in 8.6% of prostate cancers), and demonstrate interaction of the MLL complex with the AR, which is required for AR-mediated signalling. We also identified novel recurrent mutations in the AR collaborating factor FOXA1, which is mutated in 5 of 147 (3.4%) prostate cancers (both untreated localized prostate cancer and CRPC), and showed that mutated FOXA1 represses androgen signalling and increases tumour growth. Proteins that physically interact with the AR, such as the ERG gene fusion product, FOXA1, MLL2, UTX (also known as KDM6A) and ASXL1 were found to be mutated in CRPC. In summary, we describe the mutational landscape of a heavily treated metastatic cancer, identify novel mechanisms of AR signalling deregulated in prostate cancer, and prioritize candidates for future study. PMID

  16. Impact of hydrogel spacer injections on interfraction prostate motion during prostate cancer radiotherapy.

    PubMed

    Picardi, Cristina; Rouzaud, Michel; Kountouri, Melpomeni; Lestrade, Laetitia; Vallée, Jean Paul; Caparrotti, Francesca; Dubouloz, Angèle; Miralbell, Raymond; Zilli, Thomas

    2016-07-01

    Background The dosimetric advantage of prostate-rectum spacers to displace the anterior rectal wall outside of the high-dose radiation regions has been clearly established in prostate cancer radiotherapy (RT). The aim of this study was to assess the impact of hydrogel spacer (HS) in the interfraction prostate motion in patients undergoing RT for prostate cancer. Material and methods Twenty prostate cancer patients implanted with three fiducial markers (FM) with (n = 10) or without (n = 10) HS were analyzed. Displacements between the prostate isocenter based on the FM's position and the bony anatomy were quantified in the left-right (LR), anterior-posterior (AP), superior-inferior (SI) axes by offline analyses of 122 cone beam computed tomography scans. Group systematic (M), systematic (Σ) and random (σ) setup errors were determined. Results In patients with or without HS, the overall mean interfraction prostate displacements were 0.4 versus -0.4 mm (p = 0.0001), 0.6 versus 0.6 mm (p = 0.85), and -0.6 mm versus -0.3 mm (p = 0.48) for the LR, AP, and SI axes, respectively. Prostate displacements >5 mm in the AP and SI directions were similar for both groups. No differences in M, Σ and σ setup errors were observed in the three axes between HS + or HS- patients. Conclusions HS implantation does not significantly influence the interfraction prostate motion in patients treated with RT for prostate cancer. The major expected benefit of HS is a reduction of the high-dose levels to the rectal wall without influence in prostate immobilization. PMID:26796870

  17. Prostate Cancer Care Before and After Medicare Eligibility.

    PubMed

    Huesch, Marco D; Ong, Michael K

    2016-01-01

    Prior studies suggest Medicare eligibility confers significant and substantial reductions in mortality and beneficial increases in health service utilization. We compared 13,882 patients diagnosed with prostate cancer at ages 63 to 64 years with 14,774 patients diagnosed at ages 65 to 66 (controls) in 2004 to 2007. Compared with controls, patients diagnosed with prostate cancer before Medicare eligibility had no statistically significant or meaningful differences in cancer stage, time to treatment, or type of treatment. PMID:27166412

  18. The hallmarks of castration-resistant prostate cancers.

    PubMed

    Katsogiannou, Maria; Ziouziou, Hajer; Karaki, Sara; Andrieu, Claudia; Henry de Villeneuve, Marie; Rocchi, Palma

    2015-07-01

    Prostate cancer has become a real public health issue in industrialized countries, mainly due to patients' relapse by castration-refractory disease after androgen ablation. Castration-resistant prostate cancer is an incurable and highly aggressive terminal stage of prostate cancer, seriously jeopardizing the patient's quality of life and lifespan. The management of castration-resistant prostate cancer is complex and has opened new fields of research during the last decade leading to an improved understanding of the biology of the disease and the development of new therapies. Most advanced tumors resistant to therapy still maintain the androgen receptor-pathway, which plays a central role for survival and growth of most castration-resistant prostate cancers. Many mechanisms induce the emergence of the castration resistant phenotype through this pathway. However some non-related AR pathways like neuroendocrine cells or overexpression of anti-apoptotic proteins like Hsp27 are described to be involved in CRPC progression. More recently, loss of expression of tumor suppressor gene, post-transcriptional modification using miRNA, epigenetic alterations, alternatif splicing and gene fusion became also hallmarks of castration-resistant prostate cancer. This review presents an up-to-date overview of the androgen receptor-related mechanisms as well as the latest evidence of the non-AR-related mechanisms underlying castration-resistant prostate cancer progression. PMID:25981454

  19. Differentially Expressed Genes and Signature Pathways of Human Prostate Cancer

    PubMed Central

    Myers, Jennifer S.; von Lersner, Ariana K.; Robbins, Charles J.; Sang, Qing-Xiang Amy

    2015-01-01

    Genomic technologies including microarrays and next-generation sequencing have enabled the generation of molecular signatures of prostate cancer. Lists of differentially expressed genes between malignant and non-malignant states are thought to be fertile sources of putative prostate cancer biomarkers. However such lists of differentially expressed genes can be highly variable for multiple reasons. As such, looking at differential expression in the context of gene sets and pathways has been more robust. Using next-generation genome sequencing data from The Cancer Genome Atlas, differential gene expression between age- and stage- matched human prostate tumors and non-malignant samples was assessed and used to craft a pathway signature of prostate cancer. Up- and down-regulated genes were assigned to pathways composed of curated groups of related genes from multiple databases. The significance of these pathways was then evaluated according to the number of differentially expressed genes found in the pathway and their position within the pathway using Gene Set Enrichment Analysis and Signaling Pathway Impact Analysis. The “transforming growth factor-beta signaling” and “Ran regulation of mitotic spindle formation” pathways were strongly associated with prostate cancer. Several other significant pathways confirm reported findings from microarray data that suggest actin cytoskeleton regulation, cell cycle, mitogen-activated protein kinase signaling, and calcium signaling are also altered in prostate cancer. Thus we have demonstrated feasibility of pathway analysis and identified an underexplored area (Ran) for investigation in prostate cancer pathogenesis. PMID:26683658

  20. Genetic architecture of prostate cancer in the Ashkenazi Jewish population

    PubMed Central

    Vijai, J; Kirchhoff, T; Gallagher, D; Hamel, N; Guha, S; Darvasi, A; Lencz, T; Foulkes, W D; Offit, K; Klein, R J

    2011-01-01

    Background: Recently, numerous prostate cancer risk loci have been identified, some of which show association in specific populations. No study has yet investigated whether these single nucleotide polymorphisms (SNPs) are associated with prostate cancer in the Ashkenazi Jewish (AJ) population. Methods: A total of 29 known prostate cancer risk SNPs were genotyped in 963 prostate cancer cases and 613 controls of AJ ancestry. These data were combined with data from 1241 additional Ashkenazi controls and tested for association with prostate cancer. Correction for multiple testing was performed using the false discovery rate procedure. Results: Ten of twenty-three SNPs that passed quality control procedures were associated with prostate cancer risk at a false discovery rate of 5%. Of these, nine were originally discovered in studies of individuals of European ancestry. Based on power calculations, the number of significant associations observed is not surprising. Conclusion: We see no convincing evidence that the genetic architecture of prostate cancer in the AJ population is substantively different from that observed in other populations of European ancestry. PMID:21829199

  1. Prostate cancer trends in Canada: rising incidence or increased detection?

    PubMed Central

    Levy, I G; Gibbons, L; Collins, J P; Perkins, D G; Mao, Y

    1993-01-01

    OBJECTIVES: To analyse trends in the incidence and mortality rates of prostate cancer in Canada according to age distribution, temporal pattern and provincial variation; to determine any association with the rate of prostatectomy; and to determine whether any observed increase in the rate of prostate cancer was due to an increase in the detection rate. DESIGN: Descriptive epidemiologic study based on Canadian population data from 1959 to 1989 and chart review from one Canadian hospital. SETTING: The chart review was conducted at the Ottawa Civic Hospital. SUBJECTS: The data on prostate cancer trends were obtained from the Canadian population. Charts were reviewed for two groups of patients: (a) men discharged from inpatient care during 1976 and 1986-87 with prostate cancer first diagnosed in the same year and (b) men who underwent transurethral resection of the prostate (TURP) during 1976 and 1986. OUTCOME MEASURES: Incidence and mortality rates of prostate cancer, rates of prostatectomy and TURP, and correlations between them. From the hospital data, changes between 1976 and 1986-87 in distribution of cancer stages, distribution of cases detected incidentally after surgery for suspected benign prostatic hypertrophy and average number of slides analysed per gram of tissue obtained from prostatectomy. RESULTS: The epidemiologic data showed that the age-adjusted incidence rates increased by 72% overall, an increase seen in all age groups over 60 years. The mortality rates increased by 29% overall, primarily in men over 85 years old. The prostatectomy rate increased by 55%. There were significant linear correlations between the national and provincial incidence rates of prostate cancer and the TURP rates. The chart review revealed that during 1976, 53% of the cases of prostate cancer diagnosed were localized, as compared with 75% in 1986-87 (p < 0.01). The proportion of tumours diagnosed incidentally in men undergoing TURP increased by 11%, whereas the number of

  2. Tumor clone dynamics in lethal prostate cancer

    PubMed Central

    Carreira, Suzanne; Romanel, Alessandro; Goodall, Jane; Grist, Emily; Ferraldeschi, Roberta; Miranda, Susana; Prandi, Davide; Lorente, David; Frenel, Jean-Sebastien; Pezaro, Carmel; Omlin, Aurelius; Rodrigues, Daniel Nava; Flohr, Penelope; Tunariu, Nina; de Bono, Johann S.; Demichelis, Francesca; Attard, Gerhardt

    2015-01-01

    It is unclear whether a single clone metastasizes and remains dominant over the course of lethal prostate cancer. We describe the clonal architectural heterogeneity at different stages of disease progression by sequencing serial plasma and tumor samples from 16 ERG-positive patients. By characterizing the clonality of commonly occurring deletions at 21q22, 8p21, and 10q23, we identified multiple independent clones in metastatic disease that are differentially represented in tissue and circulation. To exemplify the clinical utility of our studies, we then showed a temporal association between clinical progression and emergence of androgen receptor (AR) mutations activated by glucocorticoids in about 20% of patients progressing on abiraterone and prednisolone or dexamethasone. Resistant clones showed a complex dynamic with temporal and spatial heterogeneity, suggesting distinct mechanisms of resistance at different sites that emerged and regressed depending on treatment selection pressure. This introduces a management paradigm requiring sequential monitoring of advanced prostate cancer patients with plasma and tumor biopsies to ensure early discontinuation of agents when they become potential disease drivers. PMID:25232177

  3. When Prostate Cancer Circulates in the Bloodstream

    PubMed Central

    Vlaeminck-Guillem, Virginie

    2015-01-01

    Management of patients with prostate cancer is currently based on imperfect clinical, biological, radiological and pathological evaluation. Prostate cancer aggressiveness, including metastatic potential, remains difficult to accurately estimate. In an attempt to better adapt therapeutics to an individual (personalized medicine), reliable evaluation of the intrinsic molecular biology of the tumor is warranted, and particularly for all tumor sites (primary tumors and secondary sites) at any time of the disease progression. As a consequence of their natural tendency to grow (passive invasion) or as a consequence of an active blood vessel invasion by metastase-initiating cells, tumors shed various materials into the bloodstream. Major efforts have been recently made to develop powerful and accurate methods able to detect, quantify and/or analyze all these circulating tumor materials: circulating tumors cells, disseminating tumor cells, extracellular vesicles (including exosomes), nucleic acids, etc. The aim of this review is to summarize current knowledge about these circulating tumor materials and their applications in translational research. PMID:26854164

  4. Inflammation and preneoplastic lesions in benign prostate as risk factors for prostate cancer

    PubMed Central

    Kryvenko, Oleksandr N; Jankowski, Michelle; Chitale, Dhananjay A; Tang, Deliang; Rundle, Andrew; Trudeau, Sheri; Rybicki, Benjamin A

    2013-01-01

    Benign changes ranging from atrophy and inflammation to high-grade prostatic intraepithelial neoplasia (HGPIN) are common findings on prostate core needle biopsies. Although atrophy and inflammation may be precursors of prostate cancer, only HGPIN is currently recommended to be included in surgical pathology reports. To determine whether these benign findings increase prostate cancer risk, we conducted a case–control study nested within a historical cohort of 6692 men with a benign prostate specimen collected between 1990 and 2002. The analytic sample included 574 case–control pairs comprised of cases diagnosed with prostate cancer a minimum of 1 year after cohort entry and controls matched to cases on date and age at cohort entry, race, and type of specimen. The initial benign specimen was reviewed for presence of HGPIN, atrophy (simple, lobular, and partial) and inflammation (glandular and/or stromal). HGPIN significantly increased risk for prostate cancer (odds ratio (OR) = 2.00; 95% confidence interval (CI) = 1.25–3.20). Inflammation within the stromal compartment was associated with decreased risk (OR = 0.66; CI = 0.52–0.84), and diffuse stromal inflammation of severe grade had the strongest inverse association with risk (OR = 0.21; CI = 0.07–0.62). In a model adjusted for prostate-specific antigen (PSA) level at cohort entry and inflammation, simple atrophy was associated with a 33% increased prostate cancer risk that was marginally significant (P = 0.03). Clinicians should consider patterns and extent of inflammation when managing high-risk patients with negative biopsy results. Identifying benign inflammatory processes that underlie high PSA levels would help to reduce the number of unnecessary repeated prostate biopsies. PMID:22460812

  5. MRI-Guided Prostate Biopsy of Native and Recurrent Prostate Cancer.

    PubMed

    Woodrum, David A; Gorny, Krzysztof R; Greenwood, Bernadette; Mynderse, Lance A

    2016-09-01

    Prostate cancer is the most commonly diagnosed noncutaneous cancer and second-leading cause of death in men. Many patients with clinically organ-confined prostate cancer undergo definitive, curative treatment of the whole gland with either radical prostatectomy or radiation therapy. However, many men are reluctant to take the definitive step due to potential morbidity associated with either therapy. A growing interest in active surveillance or focal therapy has emerged as realistic alternatives for many patients. With each of these management strategies, it is critical to accurately quantify and stage the cancer with improved biopsy targeting and more precise imaging with magnetic resonance imaging (MRI). Furthermore, having dependable prostate imaging allows for targeted biopsies to improve the yield of clinically significant prostate cancer and decrease detection of indolent prostate cancer. MRI-guided targeted biopsy techniques include cognitive MRI/transrectal ultrasound fusion biopsy, in-bore transrectal targeted biopsy using a calibrated guidance device, and in-bore direct MR-guided transperineal biopsy with a software-based transperineal grid template. Herein we present a contemporary review of MRI-guided targeted biopsy techniques for new and recurrent cancerous foci of the prostate. PMID:27582607

  6. Nuclear Kaiso Indicates Aggressive Prostate Cancers and Promotes Migration and Invasiveness of Prostate Cancer Cells

    PubMed Central

    Jones, Jacqueline; Wang, Honghe; Zhou, Jianjun; Hardy, Shana; Turner, Timothy; Austin, David; He, Qinghua; Wells, Alan; Grizzle, William E.; Yates, Clayton

    2013-01-01

    Kaiso, a p120 catenin-binding protein, is expressed in the cytoplasmic and nuclear compartments of cells; however, the biological consequences and clinical implications of a shift between these compartments have yet to be established. Herein, we report an enrichment of nuclear Kaiso expression in cells of primary and metastatic prostate tumors relative to the normal prostate epithelium. Nuclear expression of Kaiso correlates with Gleason score (P < 0.001) and tumor grade (P < 0.001). There is higher nuclear expression of Kaiso in primary tumor/normal matched samples and in primary tumors from African American men (P < 0.0001). We further found that epidermal growth factor (EGF) receptor up-regulates Kaiso at the RNA and protein levels in prostate cancer cell lines, but more interestingly causes a shift of cytoplasmic Kaiso to the nucleus that is reversed by the EGF receptor–specific kinase inhibitor, PD153035. In both DU-145 and PC-3 prostate cancer cell lines, Kaiso inhibition (short hairpin RNA-Kaiso) decreased cell migration and invasion even in the presence of EGF. Further, Kaiso directly binds to the E-cadherin promoter, and inhibition of Kaiso in PC-3 cells results in increased E-cadherin expression, as well as re-establishment of cell–cell contacts. In addition, Kaiso-depleted cells show more epithelial morphology and a reversal of the mesenchymal markers N-cadherin and fibronectin. Our findings establish a defined oncogenic role of Kaiso in promoting the progression of prostate cancer. PMID:22974583

  7. 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

  8. A review of prostate motion with considerations for the treatment of prostate cancer

    SciTech Connect

    Byrne, Thomas E. . E-mail: tbyrne@covhlth.com

    2005-09-30

    The motion of the prostate gland can influence the efficacy of radiation therapy. This article examines the literature concerning prostate gland motion with considerations for the treatment of cancer. The objectives of this review include providing radiation oncologists, medical physicists, and dosimetrists with data to assist in determining the best treatment adaptation for individual patients. The prostate gland is not a static structure, but rather a dynamic structure and this should be a consideration in the treatment protocol. The treatment planning personnel must add a margin to the clinical treatment volume (CTV) radiation field to account for prostate motion and patient setup errors resulting in a planning treatment volume (PTV). The movement of the prostate in a radiation field with a small margin to protect the anterior rectum may allow the posterior aspect of the gland to escape the prescribed dose. Thus, an understanding of potential prostate movements in radiation therapy is critical to achieve tumor control and minimize radiation complications in patients.

  9. [The latest research of the molecular biomarker in prostate cancer].

    PubMed

    Ashikari, Daisaku; Takahashi, Satoru

    2016-01-01

    The incidence of prostate cancer is rapidly increasing in Japan. Currently, the biomarker of prostate cancer is widely used in clinical is serum PSA only. We need to develop novel molecular markers (biomarkers) that diagnose early prostate cancer so that we can treat appropriately. Recently, the whole genome sequencing analysis has advanced that has made finding of novel molecular markers easier. The best molecular markers identified using personalized genome information will be useful to select appropriate treatment. These therapeutic options for each patient will improve the survival rate. We give an outline about the latest molecular marker basic research with reference to the articles. PMID:26793879

  10. Treatment of Metastatic Prostate Cancer in Older Adults.

    PubMed

    Loh, Kah Poh; Mohile, Supriya G; Kessler, Elizabeth; Fung, Chunkit

    2016-10-01

    The aging of the population, along with rising life expectancy, means that increasing numbers of older men will be diagnosed with prostate cancer, and a large proportion of these men will present with metastatic disease. In this paper, we discuss recent advances in prostate cancer treatment. In particular, we review management approaches for older patients with metastatic prostate cancer based on the decision tree developed by the International Society of Geriatric Oncology, which categorized older men as "fit," "vulnerable," and "frail" according to comprehensive geriatric assessment. PMID:27586377

  11. Quantify Prostate Cancer by Automated Histomorphometry

    NASA Astrophysics Data System (ADS)

    Braumann, Ulf-Dietrich; Kuska, Jens-Peer; Löffler, Markus; Wernert, Nicolas

    A new method is presented to quantify malignant changes in histological sections of prostate tissue immunohistochemically stained for prostate-specific antigen (PSA) by means of image processing. The morphological analysis of the prostate tissue uses the solidity of PSA-positive prostate tissue segments to compute a quantitative measure that turns out highly correlated with scores obtained from routine diagnosis (Gleason, Dhom).

  12. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

    PubMed Central

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R.; Tang, Dean G.

    2016-01-01

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. PMID:26924072

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

    PubMed Central

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

    2016-01-01

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

  14. Normal peripheral prostate stromal cells stimulate prostate cancer development: roles of c-kit signal

    PubMed Central

    Guo, Jian-Hua; Zhou, Juan; Zhao, Yang; Liu, Peng-Yue; Yao, Hai-Jun; Da, Jun; Zhang, Ming; Zhou, Zhe; Chen, Qi; Peng, Yu-Bing; Wang, Zhong

    2015-01-01

    Background: To investigated the peripheral stromal cell conditioned medium (CM) -stimulated c-kit-JAK2-STAT1 pathway in prostate cancer. Methods: CM harvested from normal prostate peripheral stromal cells was added to DU145 cells. DU145 cell viability and migration were measured by cell counting kit-8 reagent and Transwell analysis respectively. Colony and sphere formation efficiencies of DU145 cells co-cultured with CM from human prostate stromal cells were also measured. DU145cells were stably transfected with lentivirus-mediated shRNA for c-kit silencing. Results: C-kit expression in prostate cancer was found to be significantly higher than in benign prostatic hyperplasia and positively associated with Gleason scores. The growth, migration and capacity of clonogenic property of DU145 cells significantly increased upon exposure to peripheral stromal CM and then were inhibited after silencing the expression of c-kit. The levels of c-kit, pJAK2 and pSTAT1 were significantly induced by peripheral zone stromal CM compared with controls in serum free medium and the levels of pJAK2 and pSTAT1 decreased after c-kit silencing. Conclusions: C-kit hyper-expression promotes the development of prostate cancer. The peripheral stromal cell CM stimulated c-kit-JAK2-STAT1 pathway in prostate cancer cell viability, migration, and capacity of clonogenic property. This may lead to a greater understanding of the role of c-kit in prostate cancer and provide a potential therapeutic target for prostate cancer. PMID:26045890

  15. 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. PMID:26914149

  16. Current use of PSMA-PET in prostate cancer management.

    PubMed

    Maurer, Tobias; Eiber, Matthias; Schwaiger, Markus; Gschwend, Jürgen E

    2016-04-01

    Currently, the findings of imaging procedures used for detection or staging of prostate cancer depend on morphology of lymph nodes or bone metabolism and do not always meet diagnostic needs. Prostate-specific membrane antigen (PSMA), a transmembrane protein that has considerable overexpression on most prostate cancer cells, has gained increasing interest as a target molecule for imaging. To date, several small compounds for labelling PSMA have been developed and are currently being investigated as imaging probes for PET with the (68)Ga-labelled PSMA inhibitor Glu-NH-CO-NH-Lys(Ahx)-HBED-CC being the most widely studied agent. (68)Ga-PSMA-PET imaging in combination with multiparametric MRI (mpMRI) might provide additional molecular information on cancer localization within the prostate. In patients with primary prostate cancer of intermediate-risk to high-risk, PSMA-based imaging has been reported to improve detection of metastatic disease compared with CT or mpMRI, rendering additional cross-sectional imaging or bone scintigraphy unnecessary. Furthermore, in patients with biochemically recurrent prostate cancer, use of (68)Ga-PSMA-PET imaging has been shown to increase detection of metastatic sites, even at low serum PSA values, compared with conventional imaging or PET examination with different tracers. Thus, although current knowledge is still limited and derived mostly from retrospective series, PSMA-based imaging holds great promise to improve prostate cancer management. PMID:26902337

  17. The 22nd annual prostate cancer foundation scientific retreat report.

    PubMed

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

    2016-09-01

    The 22nd Annual Prostate Cancer Foundation (PCF) Scientific Retreat was convened in Washington, D.C. from October 8 to 10, 2015. This event is the foremost scientific conference in the world focusing on basic, translational, and clinical prostate cancer research with the highest potential for accelerating the understanding of prostate cancer biology and improving the lives and outcomes of prostate cancer patients. Topics highlighted during the 2015 Retreat included: (i) new strategies and treatments for localized high-risk, hormone-naïve, oligometastatic, castrate-resistant, and treatment-refractory prostate cancer settings; (ii) the biology and genomics of tumor heterogeneity and tumor evolution; (iii) new understandings on the mechanisms and targeting of oncogenic drivers of prostate cancer; (iv) bioengineering of novel therapies and drug delivery methods; (v) innovative approaches to tumor immunotherapy; (vi) emerging molecular imaging technologies with improved sensitivity and specificity; and (vii) advancements in prognostic and predictive biomarkers and precision medicine strategies. Prostate 76:1037-1052, 2016. © 2016 Wiley Periodicals, Inc. PMID:27272144

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

    PubMed Central

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

    2009-01-01

    Objective To assess the frequency of vitamin D deficiency among men with prostate cancer, as considerable epidemiological, in vitro, in vivo and clinical data support an association between vitamin D deficiency and prostate cancer outcome. Patients, subjects and methods The study included 120 ambulatory men with recurrent prostate cancer and 50 with clinically localized prostate cancer who were evaluated and serum samples assayed for 25-OH vitamin D levels. Then 100 controls (both sexes), matched for age and season of serum sample, were chosen from a prospective serum banking protocol. The relationship between age, body mass index, disease stage, Eastern Cooperative Oncology Group performance status, season and previous therapy on vitamin D status were evaluated using univariate and multivariate analyses. Results The mean 25-OH vitamin D level was 25.9 ng/mL in those with recurrent disease, 27.5 ng/mL in men with clinically localized prostate cancer and 24.5 ng/mL in controls. The frequency of vitamin D deficiency (< 20 ng/mL) and insufficiency (20–31 ng/mL) was 40% and 32% in men with recurrent prostate; 28% had vitamin D levels that were normal (32–100 ng/mL). Among men with localized prostate cancer, 18% were deficient, 50% were insufficient and 32% were normal. Among controls, 31% were deficient, 40% were insufficient and 29% were normal. Metastatic disease (P = 0.005) and season of blood sampling (winter/spring; P = 0.01) were associated with vitamin D deficiency in patients with prostate cancer, while age, race, performance status and body mass index were not. Conclusions Vitamin D deficiency and insufficiency were common among men with prostate cancer and apparently normal controls in the western New York region. PMID:19426195

  19. [Treatment of prostate cancer using cryoablation: a prospective study].

    PubMed

    Govorov, A V; Vasil'ev, A O; Ivanov, V Iu; Kovylina, M V; Prilepskaia, E A; Pushkar', D Iu

    2014-01-01

    Currently, the choice of tactics of treatment of the patient with prostate cancer (PCa) requires to take into account the degree of differentiation and stage of tumor, age of the patient and his somatic diseases, the risk of complications, as well as the patient's desire and physician's experience. Due to the progressive development of medical technology, interest in minimally invasive treatments for prostate cancer, such as cryoablation, interstitial brachytherapy and HIFU-therapy, has grown. Cryoablation of the prostate gland is a tissue ablation by local effects of very low temperatures and is minimally invasive, highly effective treatment for prostate cancer that can be used as the primary treatment, and in the case of tumor recurrence after radiotherapy. Focal cryoablation of the prostate allows to selectively destroy the known tumor with preservation of organ function and without reducing the quality of life of the patient. Focal therapy for prostate cancer is an alternative to radical treatment and active surveillance, occupying an intermediate position between them. Due to the lack of long-term results, focal cryoablation is an experimental type of treatment. First cryoablation of the prostate using modern equipment was carried out in Russia in March 2010, at the Department of Urology MSMSU. Since that time, we performed this procedure in 122 patients with prostate cancer; cryoablation was primary treatment in 110 patients and was used as salvage treatment in 12 patients. In most cases, the operation was performed under epidural or spinal anesthesia. According to the protocol, all the patients underwent 2 cycles of freezing and thawing under transrectal ultrasound guidance. A significant improvement of equipment for cryosurgery, the use of cryoneedles with smaller diameter, and the use of temperature sensors and catheters to warm the urethral mucosa have allowed to minimize the number of complications in comparison with other methods of treatment of

  20. 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

  1. The hedgehog/Gli signaling paradigm in prostate cancer

    PubMed Central

    Chen, Mengqian; Carkner, Richard; Buttyan, Ralph

    2011-01-01

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

  2. [Bilateral testicular metastasis of cancer of the prostate].

    PubMed

    el Moussaoui, A; Sarf, I; Dakir, M; Zamiati, S; Benjelloun, S

    1997-01-01

    Testicular metastasis of prostate cancer rarely occurs. Bilateral localization is exceptional. We report a new case of prostate adenocarcinoma with bilateral testicular metastasis. The diagnosis was made on clinical and ultrasonic arguments, and confirmed on the pathological specimen. Treatment consisted in a bilateral orchidectomy, associated with nonsteroid androgens. PMID:9765784

  3. Vitamin D, intermediary metabolism and prostate cancer tumor progression

    PubMed Central

    Wang, Wei-Lin W.; Tenniswood, Martin

    2014-01-01

    Epidemiological data have demonstrated an inverse association between serum vitamin D3 levels, cancer incidence and related mortality. However, the effects of vitamin D on prostate cancer biology and its utility for prevention of prostate cancer progression are not as well-defined. The data are often conflicting: some reports suggest that vitamin D3 induces apoptosis in androgen dependent prostate cancer cell lines, while others suggest that vitamin D3 only induces cell cycle arrest. Recent molecular studies have identified an extensive synergistic crosstalk between the vitamin D- and androgen-mediated mRNA and miRNA expression, adding an additional layer of post-transcriptional regulation to the known VDR- and AR-regulated gene activation. The Warburg effect, the inefficient metabolic pathway that converts glucose to lactate for rapid energy generation, is a phenomenon common to many different types of cancer. This process supports cell proliferation and promotes cancer progression via alteration of glucose, glutamine and lipid metabolism. Prostate cancer is a notable exception to this general process since the metabolic switch that occurs early during malignancy is the reverse of the Warburg effect. This “anti-Warburg effect” is due to the unique biology of normal prostate cells that harbor a truncated TCA cycle that is required to produce and secret citrate. In prostate cancer cells, the TCA cycle activity is restored and citrate oxidation is used to produce energy for cancer cell proliferation. 1,25(OH)2D3 and androgen together modulates the TCA cycle via transcriptional regulation of zinc transporters, suggesting that 1,25(OH)2D3 and androgen maintain normal prostate metabolism by blocking citrate oxidation. These data demonstrate the importance of androgens in the anti-proliferative effect of vitamin D in prostate cancer and highlight the importance of understanding the crosstalk between these two signaling pathways. PMID:24860512

  4. Vitamin D, intermediary metabolism and prostate cancer tumor progression.

    PubMed

    Wang, Wei-Lin W; Tenniswood, Martin

    2014-01-01

    Epidemiological data have demonstrated an inverse association between serum vitamin D3 levels, cancer incidence and related mortality. However, the effects of vitamin D on prostate cancer biology and its utility for prevention of prostate cancer progression are not as well-defined. The data are often conflicting: some reports suggest that vitamin D3 induces apoptosis in androgen dependent prostate cancer cell lines, while others suggest that vitamin D3 only induces cell cycle arrest. Recent molecular studies have identified an extensive synergistic crosstalk between the vitamin D- and androgen-mediated mRNA and miRNA expression, adding an additional layer of post-transcriptional regulation to the known VDR- and AR-regulated gene activation. The Warburg effect, the inefficient metabolic pathway that converts glucose to lactate for rapid energy generation, is a phenomenon common to many different types of cancer. This process supports cell proliferation and promotes cancer progression via alteration of glucose, glutamine and lipid metabolism. Prostate cancer is a notable exception to this general process since the metabolic switch that occurs early during malignancy is the reverse of the Warburg effect. This "anti-Warburg effect" is due to the unique biology of normal prostate cells that harbor a truncated TCA cycle that is required to produce and secret citrate. In prostate cancer cells, the TCA cycle activity is restored and citrate oxidation is used to produce energy for cancer cell proliferation. 1,25(OH)2D3 and androgen together modulates the TCA cycle via transcriptional regulation of zinc transporters, suggesting that 1,25(OH)2D3 and androgen maintain normal prostate metabolism by blocking citrate oxidation. These data demonstrate the importance of androgens in the anti-proliferative effect of vitamin D in prostate cancer and highlight the importance of understanding the crosstalk between these two signaling pathways. PMID:24860512

  5. Polygenic risk score is associated with increased disease risk in 52 Finnish breast cancer families.

    PubMed

    Muranen, Taru A; Mavaddat, Nasim; Khan, Sofia; Fagerholm, Rainer; Pelttari, Liisa; Lee, Andrew; Aittomäki, Kristiina; Blomqvist, Carl; Easton, Douglas F; Nevanlinna, Heli

    2016-08-01

    The risk of developing breast cancer is increased in women with family history of breast cancer and particularly in families with multiple cases of breast or ovarian cancer. Nevertheless, many women with a positive family history never develop the disease. Polygenic risk scores (PRSs) based on the risk effects of multiple common genetic variants have been proposed for individual risk assessment on a population level. We investigate the applicability of the PRS for risk prediction within breast cancer families. We studied the association between breast cancer risk and a PRS based on 75 common genetic variants in 52 Finnish breast cancer families including 427 genotyped women and pedigree information on ~4000 additional individuals by comparing the affected to healthy family members, as well as in a case-control dataset comprising 1272 healthy population controls and 1681 breast cancer cases with information on family history. Family structure was summarized using the BOADICEA risk prediction model. The PRS was associated with increased disease risk in women with family history of breast cancer as well as in women within the breast cancer families. The odds ratio (OR) for breast cancer within the family dataset was 1.55 [95 % CI 1.26-1.91] per unit increase in the PRS, similar to OR in unselected breast cancer cases of the case-control dataset (1.49 [1.38-1.62]). High PRS-values were informative for risk prediction in breast cancer families, whereas for the low PRS-categories the results were inconclusive. The PRS is informative in women with family history of breast cancer and should be incorporated within pedigree-based clinical risk assessment. PMID:27438779

  6. Screening for familial and hereditary prostate cancer.

    PubMed

    Lynch, Henry T; Kosoko-Lasaki, Omofolasade; Leslie, Stephen W; Rendell, Marc; Shaw, Trudy; Snyder, Carrie; D'Amico, Anthony V; Buxbaum, Sarah; Isaacs, William B; Loeb, Stacy; Moul, Judd W; Powell, Isaac

    2016-06-01

    Prostate cancer (PC) has the highest degree of genetic transmission of any form of malignancy. In some families, the hereditary pattern is so strong as to mimic an autosomal dominance trait. We reviewed the known predisposing genetic markers to assess possible strategies for screening of families at risk. We carried out a systematic literature search using the Pubmed service of the National Center for Biotechnology Information (NCBI) and several gene libraries, including the NCBI SNP Library, the Online Mendelian Inheritance in Man® Catalog of Human Genes and Genetic Disorders (OMIM) and SNPedia to obtain known gene loci, SNPs and satellite markers associated with PC. We further cross referenced information on identified loci comparing data from different articles and gene reference sites. Whenever possible, we recorded the odds ratio (OR) for the allele associated with PC. In multiple different linkage studies, many independent PC associated loci have been identified on separate chromosomes. Genome-wide association studies have added many more markers to the set derived from linkage investigations. A subset of the alleles is associated with early onset and aggressive cancer. Due to the great heterogeneity, the OR for any one allele predicting future development of this malignancy is low. The strongest predictors are the BRCA2 mutations, and the highly penetrant G84E mutation in HOXB13. The presence of multiple risk alleles is more highly predictive than a single allele. Technical limitations on screening large panels of alleles are being overcome. It is appropriate to begin supplementing prostate specific antigen testing with alleles, such as BRCA2 and HOXB13, disclosed by targeted genomic analysis in families with an unfavorable family cancer history. Future population studies of PC should include genomic sequencing protocols, particularly in families with a history of PC and other malignancies. PMID:26638190

  7. Prostate Cancer Stem-like Cells Contribute to the Development of Castration-Resistant Prostate Cancer

    PubMed Central

    Ojo, Diane; Lin, Xiaozeng; Wong, Nicholas; Gu, Yan; Tang, Damu

    2015-01-01

    Androgen deprivation therapy (ADT) has been the standard care for patients with advanced prostate cancer (PC) since the 1940s. Although ADT shows clear benefits for many patients, castration-resistant prostate cancer (CRPC) inevitably occurs. In fact, with the two recent FDA-approved second-generation anti-androgens abiraterone and enzalutamide, resistance develops rapidly in patients with CRPC, despite their initial effectiveness. The lack of effective therapeutic solutions towards CRPC largely reflects our limited understanding of the underlying mechanisms responsible for CRPC development. While persistent androgen receptor (AR) signaling under castration levels of serum testosterone (<50 ng/mL) contributes to resistance to ADT, it is also clear that CRPC evolves via complex mechanisms. Nevertheless, the physiological impact of individual mechanisms and whether these mechanisms function in a cohesive manner in promoting CRPC are elusive. In spite of these uncertainties, emerging evidence supports a critical role of prostate cancer stem-like cells (PCSLCs) in stimulating CRPC evolution and resistance to abiraterone and enzalutamide. In this review, we will discuss the recent evidence supporting the involvement of PCSLC in CRPC acquisition as well as the pathways and factors contributing to PCSLC expansion in response to ADT. PMID:26593949

  8. Prostate cancer region prediction using MALDI mass spectra

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

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

  9. Effects of Brassicaceae Isothiocyanates on Prostate Cancer.

    PubMed

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

    2016-01-01

    Despite the major progress made in the field of cancer biology, cancer is still one of the leading causes of mortality, and prostate cancer (PCa) is one of the most encountered malignancies among men. The effective management of this disease requires developing better anticancer agents with greater efficacy and fewer side effects. Nature is a large source for the development of chemotherapeutic agents, with more than 50% of current anticancer drugs being of natural origin. Isothiocyanates (ITCs) are degradation products from glucosinolates that are present in members of the family Brassicaceae. Although they are known for a variety of therapeutic effects, including antioxidant, immunostimulatory, anti-inflammatory, antiviral and antibacterial properties, nowadays, cell line and animal studies have additionally indicated the chemopreventive action without causing toxic side effects of ITCs. In this way, they can induce cell cycle arrest, activate apoptosis pathways, increase the sensitivity of resistant PCa to available chemodrugs, modulate epigenetic changes and downregulate activated signaling pathways, resulting in the inhibition of cell proliferation, progression and invasion-metastasis. The present review summarizes the chemopreventive role of ITCs with a particular emphasis on specific molecular targets and epigenetic alterations in in vitro and in vivo cancer animal models. PMID:27187332

  10. Prostate cancer incidence rates in Africa.

    PubMed

    Chu, Lisa W; Ritchey, Jamie; Devesa, Susan S; Quraishi, Sabah M; Zhang, Hongmei; Hsing, Ann W

    2011-01-01

    African American men have among the highest prostate cancer incidence rates in the world yet rates among their African counterparts are unclear. In this paper, we compared reported rates among black men of Sub-Saharan African descent using data from the International Agency for Research on Cancer (IARC) and the National Cancer Institute Surveillance, Epidemiology, and End Results Program for 1973-2007. Although population-based data in Africa are quite limited, the available data from IARC showed that rates among blacks were highest in the East (10.7-38.1 per 100,000 man-years, age-adjusted world standard) and lowest in the West (4.7-19.8). These rates were considerably lower than those of 80.0-195.3 observed among African Americans. Rates in Africa increased over time (1987-2002) and have been comparable to those for distant stage in African Americans. These patterns are likely due to differences between African and African American men in medical care access, screening, registry quality, genetic diversity, and Westernization. Incidence rates in Africa will likely continue to rise with improving economies and increasing Westernization, warranting the need for more high-quality population-based registration to monitor cancer incidence in Africa. PMID:22111004

  11. Genomic and epigenomic alterations in prostate cancer

    PubMed Central

    Aschelter, Anna M.; Giacinti, Silvana; Caporello, Paola; Marchetti, Paolo

    2012-01-01

    Prostate cancer (PC) is the second most frequently diagnosed cancer and the second leading cause of cancer deaths in man. The treatment of localized PC includes surgery or radiation therapy. In case of relapse after a definitive treatment or in patients with locally advanced or metastatic disease, the standard treatment includes the androgen-deprivation therapy (ADT). By reducing the levels of testosterone and dihydrotestosterone under the castration threshold, the ADT acts on the androgen receptor (AR), even if indirectly. The effects of the ADT are usually temporary and nearly all patients, initially sensitive to the androgen ablation therapy, have a disease progression after an 18–24 months medium term. This is probably due to the selection of the cancer cell clones and to their acquisition of critical somatic genome and epigenomic changes. This review aims to provide an overview about the genetic and epigenetic alterations having a crucial role in the carcinogenesis and in the disease progression toward the castration resistant PC. We focused on the role of the AR, on its signaling cascade and on the clinical implications that the knowledge of these aspects would have on hormonal therapy, on its failure and its toxicity. PMID:23133437

  12. 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

  13. A follow-up of cancer incidence among former Finnish dump site residents: 1999–2011

    PubMed Central

    Pukkala, Eero

    2014-01-01

    Background: In an analysis of the years 1976–1998, a 50% excess in cancer incidence was observed among residents in twelve blockhouses in Helsinki, Finland on a former dump area containing industrial and household waste. Objective: To assess cancer risk over a 13-year period 1999–2011 among residents formerly living in houses built on a dump area. Methods: All 1879 persons who ever lived in the former dump area were identified and the number of cancer cases in this population was obtained from the Finnish Cancer Registry. Results: After 5 years of residence at the dump site, the standardized incidence ratio of cancer (all sites combined) was 1.32 (95% CI: 0.94–1.79) in men and 0.53 (95% CI: 0.33–0.82) for women, in comparison with the general Helsinki population (1999–2011). No significant excess cancer risks were found. Conclusions: Residing on a former dump area was not found to result in an increased risk of cancer. PMID:25224807

  14. Statin Use Reduces Prostate Cancer All-Cause Mortality

    PubMed Central

    Sun, Li-Min; Lin, Ming-Chia; Lin, Cheng-Li; Chang, Shih-Ni; Liang, Ji-An; Lin, I-Ching; Kao, Chia-Hung

    2015-01-01

    Abstract Studies have suggested that statin use is related to cancer risk and prostate cancer mortality. We conducted a population-based cohort study to determine whether using statins in prostate cancer patients is associated with reduced all-cause mortality rates. Data were obtained from the Taiwan National Health Insurance Research Database. The study cohort comprised 5179 patients diagnosed with prostate cancer who used statins for at least 6 months between January 1, 1998 and December 31, 2010. To form a comparison group, each patient was randomly frequency-matched (according to age and index date) with a prostate cancer patient who did not use any type of statin-based drugs during the study period. The study endpoint was mortality. The hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox regression models. Among prostate cancer patients, statin use was associated with significantly decreased all-cause mortality (adjusted HR = 0.65; 95% CI = 0.60–0.71). This phenomenon was observed among various types of statin, age groups, and treatment methods. Analyzing the defined daily dose of statins indicated that both low- and high-dose groups exhibited significantly decreased death rates compared with nonusers, suggesting a dose–response relationship. The results of this population-based cohort study suggest that using statins reduces all-cause mortality among prostate cancer patients, and a dose–response relationship may exist. PMID:26426656

  15. Secondary Cancers After Radiation Therapy for Primary Prostate or Rectal Cancer.

    PubMed

    Lee, Yen-Chien; Hsieh, Chung-Cheng; Li, Chung-Yi; Chuang, Jen-Pin; Lee, Jenq-Chang

    2016-04-01

    Literature about the risk of secondary cancer after radiation therapy (RT) of prostate and rectal cancer reveals contradictory results. We conducted a meta-analysis to examine whether the RT induces secondary rectal or prostate cancer in patients, respectively, with prostate or rectal cancer. All studies published in Medline or Pubmed up to March 3, 2015, containing RT of primary rectal or prostate cancer, and providing risk estimates of secondary prostate or rectal cancer were considered as eligible. Relative risk (RR) and standardized incidence ratios (SIR) were calculated using the random-effects model. Twenty studies met the inclusion criteria. 12 of them were from the Surveillance, Epidemiology, and End Results (SEER) database. For prostate cancer patients, pooled adjusted RRs or SIRs did not show an effect on the risk of secondary rectal cancer. However, notwithstanding the limitations of SEER-based studies, the subgroup of prostate cancer patients receiving external beam radiation therapy (EBRT) showed an increased risk of rectal cancer. For rectal cancer patients, pooled adjusted RR of prostate cancer was 1.12 (95 % CI, 0.44-2.8) and SIR was 0.40 (95 % CI, 0.29-0.55). All studies included in the SIR analysis of rectal cancer were derived from the SEER data source. Based on current evidence, RT for prostate cancer patients had no effect on rectal cancer incidence, except for patients who received EBRT therapy. However, compared with the general population, RT for rectal cancer is associated with a decreased prostate cancer risk as found in SEER-based studies. PMID:26711638

  16. Progress Against Prostate Cancer | NIH MedlinePlus the Magazine

    MedlinePlus

    ... below the bladder. The urethra (the tube carrying urine from the bladder to outside the body) runs ... in size. This can narrow the urethra, decreasing urine flow. Prostate cancer is made up of cells ...

  17. Panel Endorses Active Monitoring for Low-Risk Prostate Cancer

    Cancer.gov

    An independent panel convened this week by NIH has concluded that many men with localized, low-risk prostate cancer should be closely monitored, permitting treatment to be delayed until warranted by disease progression. However, monitoring strategies—such

  18. A Urologist’s Personal View of Prostate Cancer

    PubMed Central

    Schellhammer, Paul F.

    2016-01-01

    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.

  19. AEG-1 promoter-mediated imaging of prostate cancer.

    PubMed

    Bhatnagar, Akrita; Wang, Yuchuan; Mease, Ronnie C; Gabrielson, Matthew; Sysa, Polina; Minn, Il; Green, Gilbert; Simmons, Brian; Gabrielson, Kathleen; Sarkar, Siddik; Fisher, Paul B; Pomper, Martin G

    2014-10-15

    We describe a new imaging method for detecting prostate cancer, whether localized or disseminated and metastatic to soft tissues and bone. The method relies on the use of imaging reporter genes under the control of the promoter of AEG-1 (MTDH), which is selectively active only in malignant cells. Through a systemic, nanoparticle-based delivery of the imaging construct, lesions can be identified through bioluminescence imaging and single-photon emission computed tomography in the PC3-ML murine model of prostate cancer at high sensitivity. This approach is applicable for the detection of prostate cancer metastases, including bone lesions for which there is no current reliable agent for noninvasive clinical imaging. Furthermore, the approach compares favorably with accepted and emerging clinical standards, including PET with [(18)F]fluorodeoxyglucose and [(18)F]sodium fluoride. Our results offer a preclinical proof of concept that rationalizes clinical evaluation in patients with advanced prostate cancer. PMID:25145668

  20. SPOP mutation leads to genomic instability in prostate cancer

    PubMed Central

    Boysen, Gunther; Barbieri, Christopher E; Prandi, Davide; Blattner, Mirjam; Chae, Sung-Suk; Dahija, Arun; Nataraj, Srilakshmi; Huang, Dennis; Marotz, Clarisse; Xu, Limei; Huang, Julie; Lecca, Paola; Chhangawala, Sagar; Liu, Deli; Zhou, Pengbo; Sboner, Andrea; de Bono, Johann S

    2015-01-01

    Genomic instability is a fundamental feature of human cancer often resulting from impaired genome maintenance. In prostate cancer, structural genomic rearrangements are a common mechanism driving tumorigenesis. However, somatic alterations predisposing to chromosomal rearrangements in prostate cancer remain largely undefined. Here, we show that SPOP, the most commonly mutated gene in primary prostate cancer modulates DNA double strand break (DSB) repair, and that SPOP mutation is associated with genomic instability. In vivo, SPOP mutation results in a transcriptional response consistent with BRCA1 inactivation resulting in impaired homology-directed repair (HDR) of DSB. Furthermore, we found that SPOP mutation sensitizes to DNA damaging therapeutic agents such as PARP inhibitors. These results implicate SPOP as a novel participant in DSB repair, suggest that SPOP mutation drives prostate tumorigenesis in part through genomic instability, and indicate that mutant SPOP may increase response to DNA-damaging therapeutics. DOI: http://dx.doi.org/10.7554/eLife.09207.001 PMID:26374986

  1. SPOP mutation leads to genomic instability in prostate cancer.

    PubMed

    Boysen, Gunther; Barbieri, Christopher E; Prandi, Davide; Blattner, Mirjam; Chae, Sung-Suk; Dahija, Arun; Nataraj, Srilakshmi; Huang, Dennis; Marotz, Clarisse; Xu, Limei; Huang, Julie; Lecca, Paola; Chhangawala, Sagar; Liu, Deli; Zhou, Pengbo; Sboner, Andrea; de Bono, Johann S; Demichelis, Francesca; Houvras, Yariv; Rubin, Mark A

    2015-01-01

    Genomic instability is a fundamental feature of human cancer often resulting from impaired genome maintenance. In prostate cancer, structural genomic rearrangements are a common mechanism driving tumorigenesis. However, somatic alterations predisposing to chromosomal rearrangements in prostate cancer remain largely undefined. Here, we show that SPOP, the most commonly mutated gene in primary prostate cancer modulates DNA double strand break (DSB) repair, and that SPOP mutation is associated with genomic instability. In vivo, SPOP mutation results in a transcriptional response consistent with BRCA1 inactivation resulting in impaired homology-directed repair (HDR) of DSB. Furthermore, we found that SPOP mutation sensitizes to DNA damaging therapeutic agents such as PARP inhibitors. These results implicate SPOP as a novel participant in DSB repair, suggest that SPOP mutation drives prostate tumorigenesis in part through genomic instability, and indicate that mutant SPOP may increase response to DNA-damaging therapeutics. PMID:26374986

  2. Enzalutamide Improves Survival in Patients with Metastatic Prostate Cancer

    Cancer.gov

    A summary of results from an international phase III trial that compared enzalutamide (Xtandi®) and placebo for the treatment of metastatic prostate cancer that had progressed during treatment with androgen deprivation therapy.

  3. Men with Advanced Prostate Cancer Might Consider Gene Test

    MedlinePlus

    ... html Men With Advanced Prostate Cancer Might Consider Gene Test Detection of genetic flaw could help predict ... suggests. Testing for inherited abnormalities in DNA repair genes could provide patients and family members important information ...

  4. Spontaneous circadian fluctuations of prostate specific antigen and prostatic acid phosphatase serum activities in patients with prostatic cancer.

    PubMed

    Mannini, D; Maver, P; Aiello, E; Corrado, G; Vecchi, F; Bellanova, B; Marengo, M

    1988-01-01

    Spontaneous circadian variations of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP), determined simultaneously by radioimmunoassay (RIA), were investigated by multiple sampling, over a 24-hour period, in 32 patients with prostatic cancer. In 29/32 patients (91%), the coefficient of variation of 24-hour values, for either marker, was greater than that of the RIA method at the same range of values; stage D patients showed the greatest spontaneous variability. Fluctuations around the mean of 24-hour values ranged from -65% to +85% for PAP, from -72% to +190% for PSA, occurring random and independently for each marker. Variability was about 20% greater for PSA than for PAP. The existence of spontaneous fluctuations should be considered in multiple marker evaluation of prostatic cancer patients. PMID:2449758

  5. ZINC AND ZINC TRANSPORTERS IN NORMAL PROSTATE FUNCTION AND THE PATHOGENESIS OF PROSTATE CANCER

    PubMed Central

    Franklin, Renty B.; Milon, Beatrice; Feng, Pei; Costello, Leslie C.

    2015-01-01

    Zinc is an essential metal for all cells. It plays a role in a wide variety of physiological and biochemical processes. In the prostate epithelial cell the accumulation of high cellular zinc is a specialized function that is necessary for these cells to carry out the major physiological functions of production and secretion of citrate. The production of citrate and its secretion into prostatic fluid is a differentiated function of the prostate epithelial cells that is apparently important for reproduction. The loss of citrate and zinc accumulation is the most consistent and persistent characteristic of prostate malignancy. This characteristic of prostate cancer indicates that the lost ability of the malignant cells to accumulate zinc and citrate is an important factor in the development and progression of malignancy. The lost ability of the epithelial cells to accumulate zinc and thus to also accumulate citrate is the result of decreased expression of specific zinc uptake transporters. The purpose of this presentation is to review the current understanding of zinc and zinc homeostasis in the prostate and the role of zinc and zinc transporters in the normal function of the prostate and the pathogenesis of prostate cancer. PMID:15970489

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

    Cancer.gov

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

  7. Potential role of gastrointestinal microbiota composition in prostate cancer risk

    PubMed Central

    2013-01-01

    Background Among men in the U.S., prostate cancer is the most common cancer and the second leading cause of cancer death. Despite its prevalence, there are few established risk factors for prostate cancer. Some studies have found that intake of certain foods/nutrients may be associated with prostate cancer risk, but few have accounted for how intake and metabolic factors may interact to influence bioavailable nutrient levels and subsequent disease risk. Presentation of the hypothesis The composition of the gastrointestinal (GI) microbiome may influence metabolism of dietary compounds and nutrients (e.g., plant phenols, calcium, choline) that may be relevant to prostate cancer risk. We, therefore, propose the hypothesis that GI microbiota may have a markedly different composition among individuals with higher prostate cancer risk. These individuals could have microbial profiles that are conducive to intestinal inflammation and/or are less favorable for the metabolism and uptake of chemopreventive agents. Testing the hypothesis Because very little preliminary data exist on this potential association, a case–control study may provide valuable information on this topic. Such a study could evaluate whether the GI microbial profile is markedly different between three groups of individuals: healthy men, those with latent prostate cancer, and those with invasive prostate cancer. Any findings could then be validated in a larger study, designed to collect a series of specimens over time. Implications of the hypothesis Given the plethora of information emerging from the Human Microbiome Project, this is an opportune time to explore associations between the microbiome and complex human diseases. Identification of profiles that alter the host’s risk for disease may clarify inconsistencies in the literature on dietary factors and cancer risk, and could provide valuable targets for novel cancer prevention strategies. PMID:24180596

  8. Lethal Prostate Cancer in the PLCO Cancer Screening Trial.

    PubMed

    Shoag, Jonathan; Mittal, Sameer; Halpern, Joshua A; Scherr, Douglas; Hu, Jim C; Barbieri, Christopher E

    2016-07-01

    The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial randomized men to usual care or annual prostate-specific antigen (PSA) screening for 6 yr and digital rectal examination for 4 yr. This trial found no difference between the intervention and usual care arms of the study in the primary end point of prostate cancer (PCa)-specific mortality. The PLCO trial results have had a major impact on health policy and the rate of PSA screening in the United States. We analyzed the 13-yr screening and outcomes data from the 151 participants who died of PCa in the screening arm of the trial to better understand how randomization to screening failed to prevent PCa death in these men. We found that of these men, 81 (53.6%) either were never screened as part of the trial or had an initial positive screen. Only 17 (11.3%) of those who died reached year 6 of the trial with a PSA <4.0 ng/ml. The men who died in the screening arm were also older at study entry than the average PLCO participant (66 vs 62 yr; p < 0.001). Our analysis should inform the interpretation of the PLCO trial and provide insight into future trial design. PMID:27166670

  9. PBX3 is a putative biomarker of aggressive prostate cancer.

    PubMed

    Ramberg, Håkon; Grytli, Helene Hartvedt; Nygård, Ståle; Wang, Wanzhong; Ögren, Olov; Zhao, Sen; Løvf, Marthe; Katz, Betina; Skotheim, Rolf I; Bjartell, Anders; Eri, Lars Magne; Berge, Viktor; Svindland, Aud; Taskén, Kristin Austlid

    2016-10-15

    There is a great need to identify new and better prognostic and predictive biomarkers to stratify prostate cancer patients for optimal treatment. The aims of this study were to characterize the expression profile of pre-B cell leukemia homeobox (PBX) transcription factors in prostate cancer with an emphasis on investigating whether PBX3 harbours any prognostic value. The expression profile of PBX3 and PBX1 in prostate tissue was determined by immunohistochemical and immunoblot analysis. Furthermore, the expression of PBX3 transcript variants was analyzed by RT-PCR, NanoString Technologies®, and by analyzing RNA sequence data. The potential of PBX3 to predict prognosis, either at mRNA or protein level, was studied in four independent cohorts. PBX3 was mainly expressed in the nucleus of normal prostate basal cells, while it showed cytosolic expression in prostatic intraepithelial neoplasia and cancer cells. We detected four PBX3 transcript variants in prostate tissue. Competing risk regression analysis revealed that high PBX3 expression was associated with slower progression to castration resistant prostate cancer (sub-hazard ratio (SHR) 0.18, 95% CI: 0.081-0.42, p values < 0.001). PBX3 expression had a high predictive accuracy (area under the curve (AUC) = 0.82) when combined with Gleason score and age. Patients undergoing radical prostatectomy, with high levels of PBX3 mRNA, had improved prostate cancer specific survival compared to patients expressing low levels (SHR 0.21, 95% CI: 0.46-0.93, p values < 0.001, and AUC = 0.75). Our findings strongly indicate that PBX3 has potential as a biomarker, both as part of a larger gene panel and as an immunohistochemical marker, for aggressive prostate cancer. PMID:27273830

  10. The diet as a cause of human prostate cancer.

    PubMed

    Nelson, William G; Demarzo, Angelo M; Yegnasubramanian, Srinivasan

    2014-01-01

    Asymptomatic prostate inflammation and prostate cancer have reached epidemic proportions among men in the developed world. Animal model studies implicate dietary carcinogens, such as the heterocyclic amines from over-cooked meats and sex steroid hormones, particularly estrogens, as candidate etiologies for prostate cancer. Each acts by causing epithelial cell damage, triggering an inflammatory response that can evolve into a chronic or recurrent condition. This milieu appears to spawn proliferative inflammatory atrophy (PIA) lesions, a type of focal atrophy that represents the earliest of prostate cancer precursor lesions. Rare PIA lesions contain cells which exhibit high c-Myc expression, shortened telomere segments, and epigenetic silencing of genes such as GSTP1, encoding the π-class glutathione S-transferase, all characteristic of prostatic intraepithelial neoplasia (PIN) and prostate cancer. Subsequent genetic changes, such as the gene translocations/deletions that generate fusion transcripts between androgen-regulated genes (such as TMPRSS2) and genes encoding ETS family transcription factors (such as ERG1), arise in PIN lesions and may promote invasiveness characteristic of prostatic adenocarcinoma cells. Lethal prostate cancers contain markedly corrupted genomes and epigenomes. Epigenetic silencing, which seems to arise in response to the inflamed microenvironment generated by dietary carcinogens and/or estrogens as part of an epigenetic "catastrophe" affecting hundreds of genes, persists to drive clonal evolution through metastatic dissemination. The cause of the initial epigenetic "catastrophe" has not been determined but likely involves defective chromatin structure maintenance by over-exuberant DNA methylation or histone modification. With dietary carcinogens and estrogens driving pro-carcinogenic inflammation in the developed world, it is tempting to speculate that dietary components associated with decreased prostate cancer risk, such as intake of

  11. Calcium intake increases risk of prostate cancer among Singapore Chinese

    PubMed Central

    Butler, Lesley M.; Wong, Alvin S.; Koh, Woon-Puay; Wang, Renwei; Yuan, Jian-Min; Yu, Mimi C.

    2010-01-01

    Consumption of dairy products, the primary source of calcium in Western diets, has been found to be positively associated with prostate cancer. In an Asian diet, non-dairy foods are the major contributors of calcium. Thus, a study of dietary calcium and prostate cancer in Asians can better inform on whether calcium, as opposed to other dairy components is responsible for the dairy foods-prostate cancer association. We examined calcium intake and prostate cancer risk among 27,293 men of the Singapore Chinese Health Study that was established between 1993 and 1998. As of December 31, 2007, 298 incident prostate cancer cases had been diagnosed among the cohort members. Diet was assessed at baseline with a validated 165-item food frequency questionnaire. It is hypothesized that there is greater net absorption of calcium in smaller individuals. Therefore, the calcium-prostate cancer association was also assessed in stratified analyses by median body mass index (BMI). Vegetables were the largest contributor of daily calcium intake in the study population. Overall, we observed a modest, statistically nonsignificant 25% increase in prostate cancer risk for the 4th (median = 659 mg/day) versus 1st (median=211 mg/day) quartiles of calcium intake after adjustment for potential confounders. The association became considerably stronger and achieved statistical significance (hazard ratio=2.03; 95% confidence interval: 1.23, 3.34; P for trend=0.01) for men with below median (22.9 kg/m2) BMI. Dietary calcium may be a risk factor for prostate cancer even at relatively low intake. PMID:20516117

  12. Perspectives on the clinical management of localized prostate cancer

    PubMed Central

    Nelson, Joel B

    2014-01-01

    If cure is necessary, is it possible and if cure is possible, is it necessary?’-Willet F. Whitmore Defined broadly, prostate cancer has two states: An indolent histological manifestation of a locally proliferative and invasive process or a clinically relevant, potentially lethal disease. Likewise, the management of clinically localized prostate cancer must address two questions: what sort of disease is this and what needs to be done. PMID:24589461

  13. Immune Response to Sipuleucel-T in Prostate Cancer

    PubMed Central

    Thara, Eddie; Dorff, Tanya B.; Averia-Suboc, Monica; Luther, Michael; Reed, Mary E.; Pinski, Jacek K.; Quinn, David I.

    2012-01-01

    Historically, chemotherapy has remained the most commonly utilized therapy in patients with metastatic cancers. In prostate cancer, chemotherapy has been reserved for patients whose metastatic disease becomes resistant to first line castration or androgen deprivation. While chemotherapy palliates, decreases serum prostate specific antigen and improves survival, it is associated with significant side effects and is only suitable for approximately 60% of patients with castrate-resistant prostate cancer. On that basis, exploration of other therapeutic options such as active secondary hormone therapy, bone targeted treatments and immunotherapy are important. Until recently, immunotherapy has had no role in the treatment of solid malignancies aside from renal cancer and melanoma. The FDA-approved autologous cellular immunotherapy sipuleucel-T has demonstrated efficacy in improving overall survival in patients with metastatic castrate-resistant prostate cancer in randomized clinical trials. The proposed mechanism of action is reliant on activating the patients’ own antigen presenting cells (APCs) to prostatic acid phosphatase (PAP) fused with granulocyte-macrophage colony stimulating factor (GM-CSF) and subsequent triggered T-cell response to PAP on the surface of prostate cancer cells in the patients body. Despite significant prolongation of survival in Phase III trials, the challenge to health care providers remains the dissociation between objective changes in serum PSA or on imaging studies after sipleucel-T and survival benefit. On that basis there is an unmet need for markers of outcome and a quest to identify immunologic or clinical surrogates to fill this role. This review focuses on the impact of sipuleucel-T on the immune system, the T and B cells, and their responses to relevant antigens and prostate cancer. Other therapeutic modalities such as chemotherapy, corticosteroids and GM-CSF and host factors can also affect immune response. The optimal timing for

  14. Detection of micrometastatic prostate cancer cells in the bone marrow of patients with prostate cancer.

    PubMed Central

    Deguchi, T.; Yang, M.; Ehara, H.; Ito, S.; Nishino, Y.; Takahashi, Y.; Ito, Y.; Shimokawa, K.; Tanaka, T.; Imaeda, T.; Doi, T.; Kawada, Y.

    1997-01-01

    Thirty-five patients with prostate cancer were examined for micrometastases to the bone marrow using reverse transcription-polymerase chain reaction (RT-PCR) with primers specific for the prostate-specific antigen (PSA) gene. Of nine patients with bone metastases detectable by bone scan imaging, five patients had PSA mRNA expression in the bone marrow detectable by RT-PCR. Of 26 patients with negative bone scan findings, seven patients had PSA mRNA expression detectable in the bone marrow. RT-PCR could detect micrometastatic prostate cancer cells in the bone marrow that were not detectable by bone scan imaging. Of 16 patients with a serum PSA concentration of 25 ng ml(-1) or greater, only nine (56.3%) had bone metastases detected by bone scans. Of the remaining seven patients, five had micrometastases to the bone marrow detected by RT-PCR. Overall, 14 of 16 patients (87.5%) with a serum PSA concentration of 25 ng ml(-1) or greater had metastatic bone diseases including bone marrow micrometastases. Of 19 patients with a serum PSA concentration of less than 25 ng ml(-1), two (10.5%) had only micrometastatic disease detected by RT-PCR. A significant correlation was observed between the incidence of bone involvement and the serum PSA concentration. This study suggests that RT-PCR will potentially develop into a relevant tool to assess bone involvement including bone marrow micrometastases and establish a precise correlation between serum PSA concentration and metastatic bone disease in patients with prostate cancer. Images Figure 1 PMID:9043017

  15. Methylation in benign prostate and risk of disease progression in men subsequently diagnosed with prostate cancer.

    PubMed

    Rybicki, Benjamin A; Rundle, Andrew; Kryvenko, Oleksandr N; Mitrache, Nicoleta; Do, Kieu C; Jankowski, Michelle; Chitale, Dhananjay A; Trudeau, Sheri; Belinsky, Steven A; Tang, Deliang

    2016-06-15

    In DNA from prostate tumors, methylation patterns in gene promoter regions can be a biomarker for disease progression. It remains unclear whether methylation patterns in benign prostate tissue--prior to malignant transformation--may provide similar prognostic information. To determine whether early methylation events predict prostate cancer outcomes, we evaluated histologically benign prostate specimens from 353 men who eventually developed prostate cancer and received "definitive" treatment [radical prostatectomy (58%) or radiation therapy (42%)]. Cases were drawn from a large hospital-based cohort of men with benign prostate biopsy specimens collected between 1990 and 2002. Risk of disease progression associated with methylation was estimated using time-to-event analyses. Average follow-up was over 5 years; biochemical recurrence (BCR) occurred in 91 cases (26%). In White men, methylation of the APC gene was associated with increased risk of BCR, even after adjusting for standard clinical risk factors for prostate cancer progression (adjusted hazard ratio (aHR) = 2.26; 95%CI 1.23-4.16). APC methylation was most strongly associated with a significant increased risk of BCR in White men with low prostate specific antigen at cohort entry (HR = 3.66; 95%CI 1.51-8.85). In additional stratified analyses, we found that methylation of the RARB gene significantly increased risk of BCR in African American cases who demonstrated methylation of at least one of the other four genes under study (HR = 3.80; 95%CI 1.07-13.53). These findings may have implications in the early identification of aggressive prostate cancer as well as reducing unnecessary medical procedures and emotional distress for men who present with markers of indolent disease. PMID:26860439

  16. Hydrodynamic stretching for prostate cancer detection

    NASA Astrophysics Data System (ADS)

    Belotti, Yuri; Conneely, Michael; Palmer, Scott; Huang, Tianjun; Campbell, Paul; McKenna, Stephen; Nabi, Ghulam; McGloin, David

    2015-06-01

    Advances in diagnostic technologies enabled scientists to link a large number of diseases with structural changes of the intracellular organisation. This intrinsic biophysical characteristic opened up the possibility to perform clinical assessments based on the measurement of single-cell mechanical properties. In this work, we combine microfluidics, high speed imaging and computational automatic tracking to measure the single-cell deformability of large samples of prostate cancer cells at a rate of ~ 104cells/s. Such a high throughput accounts for the inherent heterogeneity of biological samples and enabled us to extract statistically meaningful signatures from each cell population. In addition, using our technique we investigate the effect of Latrunculin A to the cellular stiffness.

  17. [Advancement in the treatment against prostate cancer].

    PubMed

    Shinohara, Nobuo; Abe, Takashige; Maruyama, Satoru

    2016-01-01

    With the advancement of basic science and medical technology, the treatment against prostate cancer (PC) has dramatically changed. Although the introduction of robotic radical prostatectomy and particle therapies in patients with early stage PC is of much note, the issues on the over-treatment and treatment cost should be heeded. From these points, active surveillance has been an important strategy in these patients. In patients with metastatic hormone-sensitive PC, especially high volume metastases, androgen deprivation therapy (ADT) with docetaxel has been reported to prolong overall survival compared with ADT alone. Lastly, several novel therapeutic agents have been investigated and shown to be favorable outcomes in patients with castration resistant PC. This review focuses on the recent advancement in the treatment against PCs. PMID:26793875

  18. MicroRNAs and drug resistance in prostate cancers.

    PubMed

    Li, Feng; Mahato, Ram I

    2014-08-01

    Prostate cancer is the second leading cause of cancer related death in American men. Androgen deprivation therapy (ADT) is used to treat patients with aggressive prostate cancers. After androgen deprivation therapy, prostate cancers slowly progress to an androgen-independent status. Taxanes (e.g., docetaxel) are used as standard treatments for androgen-independent prostate cancers. However, these chemotherapeutic agents will eventually become ineffective due to the development of drug resistance. A microRNA (miRNA) is a small noncoding RNA molecule, which can regulate gene expression at the post-transcription level. miRNAs elicit their effects by binding to the 3'-untranslated region (3'-UTR) of their target mRNAs, leading to the inhibition of translation or the degradation of the mRNAs. miRNAs have received increasing attention as targets for cancer therapy, as they can target multiple signaling pathways related to tumor progression, metastasis, invasion, and chemoresistance. Emerging evidence suggests that aberrant expression of miRNAs can lead to the development of resistant prostate cancers. Here, we discuss the roles of miRNAs in the development of resistant prostate cancers and their involvement in various drug resistant mechanisms including androgen signaling, apoptosis avoidance, multiple drug resistance (MDR) transporters, epithelialmesenchymal transition (EMT), and cancer stem cells (CSCs). In addition, we also discuss strategies for treating resistant prostate cancers by targeting specific miRNAs. Different delivery strategies are also discussed with focus on those that have been successfully used in human clinical trials. PMID:24742219

  19. Detection of prostate cancer using a voltammetric electronic tongue.

    PubMed

    Pascual, Lluís; Campos, Inmaculada; Vivancos, José-Luis; Quintás, Guillermo; Loras, Alba; Martínez-Bisbal, M Carmen; Martínez-Máñez, Ramón; Boronat, Francisco; Ruiz-Cerdà, José Luis

    2016-08-01

    A simple method based on the multivariate analysis of data from urine using an electronic voltammetric tongue is used to detect patients with prostate cancer. A sensitivity of 91% and a specificity of 73% were obtained to distinguish the urine from cancer patients and the urine from non-cancer patients. PMID:27375181

  20. Impact of Candidate Genetic Polymorphisms in Prostate Cancer: An Overview.

    PubMed

    Salvi, S; Conteduca, V; Gurioli, G; Calistri, D; Casadio, V; De Giorgi, U

    2016-02-01

    In the last few years, the presence of single nucleotide polymorphisms (SNPs) has been investigated in many tumors as predictor of disease aggressiveness and clinical outcome. We searched for relevant articles from 1998 to 2015 about the impact of SNPs in prostate cancer. Particularly, in this article, we review the pathogenetic, prognostic and predictive significance of gene polymorphisms in prostate tumor, providing a brief overview of studies in which the possible role of genetic variants was investigated in clinical settings. Because conflicting results often emerge about the impact of gene polymorphisms in prostate cancer, further larger studies are warranted in order to introduce gene polymorphism into clinical practice as biomarkers. PMID:26518421

  1. Lycopene modulates growth and survival associated genes in prostate cancer.

    PubMed

    Rafi, Mohamed M; Kanakasabai, Saravanan; Reyes, Marynell D; Bright, John J

    2013-10-01

    Lycopene is a fat soluble red-orange carotenoid pigment present in tomato that reduces the risk for prostate cancer, a common malignancy among men. However, the mechanism by which lycopene attenuates prostate cancer is not fully defined. In this study we examined the effect of lycopene on proliferation, survival, and biomarker gene expression in prostate cancer (PC-3) cells in culture. WST-1 assay showed that lycopene induces a biphasic effect on PC-3 cells with a modest increase in proliferation at 1-5 μM, no change at 10-25 μM and a decrease at 50-100 μM doses in culture. Interestingly, combination treatment with lycopene induced anti-proliferative effect of Temozolomide on PC-3 cells. Lycopene also augmented the anti-proliferative effect of peroxisome proliferator-activated receptor gamma (PPARγ) agonists, but not Doxorubicin or Taxol, in prostate cancer. Flow cytometry analyses showed that lycopene, in combination with chemotherapeutic agents and PPARγ agonists, induced modest cell cycle arrest with significant increase in cell death by apoptosis and necrosis on prostate cancer. Gene array and quantitative reverse transcription polymerase chain reaction analyses showed that lycopene alters the expression of growth and apoptosis associated biomarkers in PC-3 cells. These findings highlight that lycopene attenuates prostate cancer by modulating the expression of growth and survival associated genes. PMID:23746934

  2. [Treatment strategy for advanced prostate cancer with bone metastases].

    PubMed

    Sugimoto, Mikio; Kakehi, Yoshiyuki

    2006-08-01

    The introduction of PSA screening has led to confirming a shift towards an earlier pathological stage in the diagnosis of prostate cancer. Consequently, the proportion of detecting early stage prostate cancer has clearly been increasing. On the other hand, progressive cancers in the form of distant metastases and locally advanced ones that have been confirmed at the initial diagnosis exhibit a constant rate. In addition, there have been a lot of cases where hormonal resistance was acquired during hormonal therapy which resulted in advanced metastases of the prostate. Prostate cancer has a tendency to be metastatic to bones. Combining the fact that the survival period of patients undergoing treatment is prolonged after metastases, the length of suffering caused by complications, such as ostealgia, pathological fracture and myelopathy, becomes an issue in which QOL and ADL of the patient are sacrificed for a long time. As for treatment of prostate cancer with metastases, a palliative treatment is common in the clinical scene. However, we can extend a life prognosis with use of radiotherapy and surgical treatment in addition to the palliative treatment at an appropriate time. It appears that a combination of new chemotherapy and hormonal therapy will be promising. In the future, we believe that the appearance of new anticancer drugs, endocrine therapies, bisphosphonates and strontium treatment could be used as a part of the treatment strategy for prostate cancer with bone metastases. PMID:16912523

  3. 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. PMID:25800589

  4. Characterization of aggressive prostate cancer using ultrasound RF time series

    NASA Astrophysics Data System (ADS)

    Khojaste, Amir; Imani, Farhad; Moradi, Mehdi; Berman, David; Siemens, D. Robert; Sauerberi, Eric E.; Boag, Alexander H.; Abolmaesumi, Purang; Mousavi, Parvin

    2015-03-01

    Prostate cancer is the most prevalently diagnosed and the second cause of cancer-related death in North American men. Several approaches have been proposed to augment detection of prostate cancer using different imaging modalities. Due to advantages of ultrasound imaging, these approaches have been the subject of several recent studies. This paper presents the results of a feasibility study on differentiating between lower and higher grade prostate cancer using ultrasound RF time series data. We also propose new spectral features of RF time series to highlight aggressive prostate cancer in small ROIs of size 1 mm × 1 mm in a cohort of 19 ex vivo specimens of human prostate tissue. In leave-one-patient-out cross-validation strategy, an area under accumulated ROC curve of 0.8 has been achieved with overall sensitivity and specificity of 81% and 80%, respectively. The current method shows promising results on differentiating between lower and higher grade of prostate cancer using ultrasound RF time series.

  5. Model-based patterns in prostate cancer mortality worldwide

    PubMed Central

    Fontes, F; Severo, M; Castro, C; Lourenço, S; Gomes, S; Botelho, F; La Vecchia, C; Lunet, N

    2013-01-01

    Background: Prostate cancer mortality has been decreasing in several high income countries and previous studies analysed the trends mostly according to geographical criteria. We aimed to identify patterns in the time trends of prostate cancer mortality across countries using a model-based approach. Methods: Model-based clustering was used to identify patterns of variation in prostate cancer mortality (1980–2010) across 37 European, five non-European high-income countries and four leading emerging economies. We characterised the patterns observed regarding the geographical distribution and gross national income of the countries, as well as the trends observed in mortality/incidence ratios. Results: We identified three clusters of countries with similar variation in prostate cancer mortality: pattern 1 (‘no mortality decline'), characterised by a continued increase throughout the whole period; patterns 2 (‘later mortality decline') and 3 (‘earlier mortality decline') depict mortality declines, starting in the late and early 1990s, respectively. These clusters are also homogeneous regarding the variation in the prostate cancer mortality/incidence ratios, while are heterogeneous with reference to the geographical region of the countries and distribution of the gross national income. Conclusion: We provide a general model for the description and interpretation of the trends in prostate cancer mortality worldwide, based on three main patterns. PMID:23660943

  6. Multiparametric Magnetic Resonance Imaging of Recurrent Prostate Cancer

    PubMed Central

    Oppenheimer, Daniel Corey; Weinberg, Eric P; Hollenberg, Gary M; Meyers, Steven P

    2016-01-01

    Multiparametric magnetic resonance (MR) imaging of the prostate combines both morphological and functional MR techniques by utilizing small field of view T1-weighted, T2-weighted, diffusion-weighted imaging, dynamic contrast-enhanced imaging, and MR spectroscopy to accurately detect, localize, and stage primary and recurrent prostate cancer. Localizing the site of recurrence in patients with rising prostate-specific antigen following treatment affects decision making regarding treatment and can be accomplished with multiparametric prostate MR. Several different treatment options are available for prostate cancer including radical prostatectomy, external beam radiation therapy, brachytherapy, androgen deprivation therapy, or a number of focal therapy techniques. The findings of recurrent prostate cancer can be different depending on the treatment the patient has received, and the radiologist must be able to recognize the variety of imaging findings seen with this common disease. This review article will detail the findings of recurrent prostate cancer on multiparametric MR and describe common posttreatment changes which may create challenges to accurate interpretation. PMID:27195184

  7. Copy number alteration burden predicts prostate cancer relapse

    PubMed Central

    Hieronymus, Haley; Schultz, Nikolaus; Gopalan, Anuradha; Carver, Brett S.; Chang, Matthew T.; Xiao, Yonghong; Heguy, Adriana; Huberman, Kety; Bernstein, Melanie; Assel, Melissa; Murali, Rajmohan; Vickers, Andrew; Scardino, Peter T.; Sander, Chris; Reuter, Victor; Taylor, Barry S.; Sawyers, Charles L.

    2014-01-01

    Primary prostate cancer is the most common malignancy in men but has highly variable outcomes, highlighting the need for biomarkers to determine which patients can be managed conservatively. Few large prostate oncogenome resources currently exist that combine the molecular and clinical outcome data necessary to discover prognostic biomarkers. Previously, we found an association between relapse and the pattern of DNA copy number alteration (CNA) in 168 primary tumors, raising the possibility of CNA as a prognostic biomarker. Here we examine this question by profiling an additional 104 primary prostate cancers and updating the initial 168 patient cohort with long-term clinical outcome. We find that CNA burden across the genome, defined as the percentage of the tumor genome affected by CNA, was associated with biochemical recurrence and metastasis after surgery in these two cohorts, independent of the prostate-specific antigen biomarker or Gleason grade, a major existing histopathological prognostic variable in prostate cancer. Moreover, CNA burden was associated with biochemical recurrence in intermediate-risk Gleason 7 prostate cancers, independent of prostate-specific antigen or nomogram score. We further demonstrate that CNA burden can be measured in diagnostic needle biopsies using low-input whole-genome sequencing, setting the stage for studies of prognostic impact in conservatively treated cohorts. PMID:25024180

  8. Milk stimulates growth of prostate cancer cells in culture.

    PubMed

    Tate, Patricia L; Bibb, Robert; Larcom, Lyndon L

    2011-11-01

    Concern has been expressed about the fact that cows' milk contains estrogens and could stimulate the growth of hormone-sensitive tumors. In this study, organic cows' milk and two commercial substitutes were digested in vitro and tested for their effects on the growth of cultures of prostate and breast cancer cells. Cows' milk stimulated the growth of LNCaP prostate cancer cells in each of 14 separate experiments, producing an average increase in growth rate of over 30%. In contrast, almond milk suppressed the growth of these cells by over 30%. Neither cows' milk nor almond milk affected the growth of MCF-7 breast cancer cells or AsPC-1 pancreatic cancer cells significantly. Soy milk increased the growth rate of the breast cancer cells. These data indicate that prostate and breast cancer patients should be cautioned about the possible promotional effects of commercial dairy products and their substitutes. PMID:22043817

  9. Calcitriol in the treatment of prostate cancer.

    PubMed

    Beer, Tomasz M; Myrthue, Anne

    2006-01-01

    Calcitriol, the principal active metabolite of vitamin D and a naturally occurring hormone, showed significant antineoplastic activity in pre-clinical models of prostate cancer and many other tumor types. These antineoplastic effects were observed at calcitriol concentrations substantially above the physiological range. While a number of mechanisms of action have been postulated, the induction of apoptosis and inhibition of proliferation have been most extensively reported. These pre-clinical findings motivated several investigators to pursue a series of clinical trials to examine the potential of targeting the vitamin D receptor for cancer treatment using calcitriol. Initial studies tested daily dosing of calcitriol and showed that substantial dose escalation was not feasible due to hypercalciuria and/or hypercalcemia. In contrast, weekly dosing of calcitriol allowed substantial dose escalation without dose-limiting toxicities. Notably, however, the commercially available formulation of calcitriol exhibited nonlinear pharmacokinetics at the highest doses tested. While substantially higher concentrations were achieved, the maximum tolerated dose was not established due to this pharmacological limitation. Intermittently-dosed calcitriol was then combined with several antineoplastic agents, including steroids, bisphosphonates and chemotherapeutic agents. The activity seen in a phase II study of weekly calcitriol plus docetaxel was particularly encouraging and led to the development of DN-101, a proprietary formulation designed for cancer treatment. DN-101 in combination with docetaxel is being evaluated in a placebo-controlled randomized clinical trial that has completed accrual. PMID:16886675

  10. Prostate cancer in the elderly patient.

    PubMed

    Fung, Chunkit; Dale, William; Mohile, Supriya Gupta

    2014-08-20

    Treatment for prostate cancer (PCa) has evolved significantly over the last decade. PCa is the most prevalent non-skin cancer and the second leading cause of cancer death in men, and it has an increased incidence and prevalence in older men. As a result, physicians and patients are faced with the challenge of identifying optimal treatment strategies for localized, biochemical recurrent, and advanced PCa in the older population. When older patients are appropriately selected, treatment for PCa results in survival benefits and toxicity profiles similar to those experienced in younger patients. However, underlying health status and age-related changes can have an impact on tolerance of hormonal therapy and chemotherapy in men with advanced disease. Therefore, the heterogeneity of the elderly population necessitates a multidimensional assessment to maximize the benefit of medical and/or surgical options. Providing clinicians with the requisite health status data on which to base treatment decisions would help ensure that older patients with PCa receive optimal therapy if it will benefit them and/or active surveillance or best supportive care if it will not. We provide a review of the existing evidence to date on the management of PCa in the older population. PMID:25071137

  11. STUDY OF CYTOMEGALOVIRUS SEROSTATUS AND PROSTATE CANCER RISK IN THE PROSTATE CANCER PREVENTION TRIAL

    PubMed Central

    Sutcliffe, Siobhan; Till, Cathee; Gaydos, Charlotte A.; Jenkins, Frank J.; Goodman, Phyllis J.; Hoque, Ashraful M.; Hsing, Ann W.; Thompson, Ian M.; Zenilman, Jonathan M.; Nelson, William G.; De Marzo, Angelo M.; Platz, Elizabeth A.

    2012-01-01

    Purpose To investigate serologic evidence of infection by cytomegalovirus (CMV), a herpesvirus with known oncogenic potential that has been detected in malignant prostate tissue, in relation to prostate cancer (PCa) risk in a large case-control study nested in the Prostate Cancer Prevention Trial (PCPT). Methods Cases were men with a confirmed diagnosis of PCa after visit 2 (n=614) and controls were men not diagnosed with PCa during the trial who also had a negative end-of-study biopsy (n=616). Controls were frequency-matched to cases by age, treatment arm, and family history of PCa. Sera from visit 2 were tested for CMV IgG antibodies. Results No association was observed between CMV serostatus and PCa risk (adjusted CMV seroprevalence=67.9% for cases and 65.2% for controls, odds ratio=1.13, 95% confidence interval: 0.89–1.45). Conclusions Considering our null findings in the context of the full CMV literature, CMV infection, as measured by serostatus, does not appear to increase PCa risk. PMID:22810146

  12. Comparative uptake of polyamines by prostate and non-prostate cancer cell lines.

    PubMed

    Srinath, P; McQuarrie, S A; Suresh, M R

    2002-05-01

    The Km and Vmax of [14C]-radiolabeled polyamines were determined for PC-3 and AT3B-1 cell lines. With PC-3 Km values are in the following order: ornithine> spermidine> spermine> putrescine, while with AT3B-1 it was spermidine> ornithine> spermine> putrescine. To determine which of these polyamines exhibit higher accumulation, the relative uptake of all the four amines was studied with prostate (PC-3, AT3B-1, LNCaP) and non-prostate (MCF-7, KLN-205, OVCAR) cell lines at 10 and 20 microM after 1 hour. Spermine and spermidine accumulated at higher levels in prostate (AT3B-1 and LNCaP) over non-prostate cell lines (p < 0.01). Putrescine accumulated more in PC-3 and LNCaP than the non-prostate cancer cells. PMID:12031886

  13. N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells.

    PubMed

    Lee, John K; Phillips, John W; Smith, Bryan A; Park, Jung Wook; Stoyanova, Tanya; McCaffrey, Erin F; Baertsch, Robert; Sokolov, Artem; Meyerowitz, Justin G; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M; Shokat, Kevan M; Gustafson, W Clay; Huang, Jiaoti; Witte, Owen N

    2016-04-11

    MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance, and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention. PMID:27050099

  14. Theranostic Agents for Photodynamic Therapy of Prostate Cancer by Targeting Prostate-Specific Membrane Antigen.

    PubMed

    Wang, Xinning; Tsui, Brian; Ramamurthy, Gopolakrishnan; Zhang, Ping; Meyers, Joseph; Kenney, Malcolm E; Kiechle, Jonathan; Ponsky, Lee; Basilion, James P

    2016-08-01

    Prostatectomy has been the mainstay treatment for men with localized prostate cancer. Surgery, however, often can result in major side effects, which are caused from damage and removal of nerves and muscles surrounding the prostate. A technology that can help surgeons more precisely identify and remove prostate cancer resulting in a more complete prostatectomy is needed. Prostate-specific membrane antigen (PSMA), a type II membrane antigen highly expressed in prostate cancer, has been an attractive target for imaging and therapy. The objective of this study is to develop low molecular weight PSMA-targeted photodynamic therapy (PDT) agents, which would provide image guidance for prostate tumor resection and allow for subsequent PDT to eliminate unresectable or remaining cancer cells. On the basis of our highly negatively charged, urea-based PSMA ligand PSMA-1, we synthesized two PSMA-targeting PDT conjugates named PSMA-1-Pc413 and PSMA-1-IR700. In in vitro cellular uptake experiments and in vivo animal imaging experiments, the two conjugates demonstrated selective and specific uptake in PSMA-positive PC3pip cells/tumors, but not in PSMA-negative PC3flu cells/tumors. Further in vivo photodynamic treatment proved that the two PSMA-1-PDT conjugates can effectively inhibit PC3pip tumor progression. The two PSMA-1-PDT conjugates reported here may have the potential to aid in the detection and resection of prostate cancers. It may also allow for the identification of unresectable cancer tissue and PDT ablation of such tissue after surgical resection with potentially less damage to surrounding tissues. Mol Cancer Ther; 15(8); 1834-44. ©2016 AACR. PMID:27297866

  15. SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia

    PubMed Central

    Pearson, Helen B.; Perez-Mancera, Pedro A.; Dow, Lukas E.; Ryan, Andrew; Tennstedt, Pierre; Bogani, Debora; Elsum, Imogen; Greenfield, Andy; Tuveson, David A.; Simon, Ronald; Humbert, Patrick O.

    2011-01-01

    Loss of cellular polarity is a hallmark of epithelial cancers, raising the possibility that regulators of polarity have a role in suppressing tumorigenesis. The Scribble complex is one of at least three interacting protein complexes that have a critical role in establishing and maintaining epithelial polarity. In human colorectal, breast, and endometrial cancers, expression of the Scribble complex member SCRIB is often mislocalized and deregulated. Here, we report that Scrib is indispensable for prostate homeostasis in mice. Scrib heterozygosity initiated prostate hyperplasia, while targeted biallelic Scrib loss predisposed mice to prostate intraepithelial neoplasia. Mechanistically, Scrib was shown to negatively regulate the MAPK cascade to suppress tumorigenesis. Further analysis revealed that prostate-specific loss of Scrib in mice combined with expression of an oncogenic Kras mutation promoted the progression of prostate cancer that recapitulated the human disease. The clinical significance of the work in mice was highlighted by our observation that SCRIB deregulation strongly correlated with poor survival in human prostate cancer. These data suggest that the polarity network could provide a new avenue for therapeutic intervention. PMID:21965329

  16. Long noncoding RNAs in prostate cancer: overview and clinical implications.

    PubMed

    Malik, Bhavna; Feng, Felix Y

    2016-01-01

    Prostate cancer is the second most common cause of cancer mortality among men in the United States. While many prostate cancers are indolent, an important subset of patients experiences disease recurrence after conventional therapy and progresses to castration-resistant prostate cancer (CRPC), which is currently incurable. Thus, there is a critical need to identify biomarkers that will distinguish indolent from aggressive disease, as well as novel therapeutic targets for the prevention or treatment of CRPC. In recent years, long noncoding RNAs (lncRNAs) have emerged as an important class of biological molecules. LncRNAs are polyadenylated RNA species that share many similarities with protein-coding genes despite the fact that they are noncoding (not translated into proteins). They are usually transcribed by RNA polymerase II and exhibit the same epigenetic signatures as protein-coding genes. LncRNAs have also been implicated in the development and progression of variety of cancers, including prostate cancer. While a large number of lncRNAs exhibit tissue- and cancer-specific expression, their utility as diagnostic and prognostic biomarkers is just starting to be explored. In this review, we highlight recent findings on the functional role and molecular mechanisms of lncRNAs in the progression of prostate cancer and evaluate their use as potential biomarkers and therapeutic targets. PMID:27072044

  17. Long noncoding RNAs in prostate cancer: overview and clinical implications

    PubMed Central

    Malik, Bhavna; Feng, Felix Y

    2016-01-01

    Prostate cancer is the second most common cause of cancer mortality among men in the United States. While many prostate cancers are indolent, an important subset of patients experiences disease recurrence after conventional therapy and progresses to castration-resistant prostate cancer (CRPC), which is currently incurable. Thus, there is a critical need to identify biomarkers that will distinguish indolent from aggressive disease, as well as novel therapeutic targets for the prevention or treatment of CRPC. In recent years, long noncoding RNAs (lncRNAs) have emerged as an important class of biological molecules. LncRNAs are polyadenylated RNA species that share many similarities with protein-coding genes despite the fact that they are noncoding (not translated into proteins). They are usually transcribed by RNA polymerase II and exhibit the same epigenetic signatures as protein-coding genes. LncRNAs have also been implicated in the development and progression of variety of cancers, including prostate cancer. While a large number of lncRNAs exhibit tissue- and cancer-specific expression, their utility as diagnostic and prognostic biomarkers is just starting to be explored. In this review, we highlight recent findings on the functional role and molecular mechanisms of lncRNAs in the progression of prostate cancer and evaluate their use as potential biomarkers and therapeutic targets. PMID:27072044

  18. 3 CFR 8855 - Proclamation 8855 of August 31, 2012. National Prostate Cancer Awareness Month, 2012

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Prostate Cancer Awareness Month, 2012 8855 Proclamation 8855 Presidential Documents Proclamations Proclamation 8855 of August 31, 2012 Proc. 8855 National Prostate Cancer Awareness Month, 2012By the President of the United States of America A Proclamation Prostate cancer is among the most common cancers...

  19. 3 CFR 8552 - Proclamation 8552 of August 31, 2010. National Prostate Cancer Awareness Month, 2010

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Prostate Cancer Awareness Month, 2010 8552 Proclamation 8552 Presidential Documents Proclamations Proclamation 8552 of August 31, 2010 Proc. 8552 National Prostate Cancer Awareness Month, 2010By the President... last decade, prostate cancer is still the second leading cause of cancer deaths among men in the...

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

    Cancer.gov

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

  1. 'Charting a new course for prostate cancer' - currying favor for docetaxel in hormone-sensitive metastatic prostate cancer.

    PubMed

    Voskoboynik, Mark; Staffurth, John; Malik, Zafar; Sweeney, Christopher; Chowdhury, Simon

    2014-11-01

    Docetaxel has an established role in the treatment of metastatic castrate-resistant prostate cancer. A number of recent treatments have been shown to improve the survival outcomes for this group of patients and many with improved toxicity profiles, bringing the role of docetaxel into question. We discuss the results and implications of the CHAARTED study that demonstrated a significant improvement in overall survival with docetaxel in metastatic hormone-sensitive prostate cancer. PMID:25353342

  2. Prospective evaluation of serum sarcosine and risk of prostate cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

    PubMed Central

    Koutros, Stella; Hsing, Ann W.; Berndt, Sonja I.

    2013-01-01

    Metabolomic profiling has identified, sarcosine, a derivative of the amino acid glycine, as an important metabolite involved in the etiology or natural history of prostate cancer. We examined the association between serum sarcosine levels and risk of prostate cancer in 1122 cases (813 non-aggressive and 309 aggressive) and 1112 controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Sarcosine was quantified using high-throughput liquid chromatography–mass spectrometry. A significantly increased risk of prostate cancer was observed with increasing levels of sarcosine (odds ratio [OR] for the highest quartile of exposure [Q4] versus the lowest quartile [Q1] = 1.30, 95% confidence interval [CI]: 1.02, 1.65; P-trend 0.03). When stratified by disease aggressiveness, we observed a stronger association for non-aggressive cases (OR for Q4 versus Q1 = 1.44, 95% CI: 1.11, 1.88; P-trend 0.006) but no association for aggressive prostate cancer (OR for Q4 versus Q1 = 1.03, 95% CI: 0.73, 1.47; P-trend 0.89). Although not statistically significant, temporal analyses showed a stronger association between sarcosine and prostate cancer for serum collected closer to diagnosis, suggesting that sarcosine may be an early biomarker of disease. Interestingly, the association between sarcosine and prostate cancer risk was stronger among men with diabetes (OR = 2.66, 95% CI: 1.04, 6.84) compared with those without reported diabetes (OR = 1.23, 95% CI: 0.95–1.59, P-interaction = 0.01). This study found that elevated levels of serum sarcosine are associated with an increased prostate cancer risk and evidence to suggest that sarcosine may be an early biomarker for this disease. PMID:23698636

  3. Toxicity Profile With a Large Prostate Volume After External Beam Radiotherapy for Localized Prostate Cancer

    SciTech Connect

    Pinkawa, Michael Fischedick, Karin; Asadpour, Branka; Gagel, Bernd; Piroth, Marc D.; Nussen, Sandra; Eble, Michael J.

    2008-01-01

    Purpose: To assess the impact of prostate volume on health-related quality of life (HRQOL) before and at different intervals after radiotherapy for prostate cancer. Methods and Materials: A group of 204 patients was surveyed prospectively before (Time A), at the last day (Time B), 2 months after (Time C), and 16 months (median) after (Time D) radiotherapy, with a validated questionnaire (Expanded Prostate Cancer Index Composite). The group was divided into subgroups with a small (11-43 cm{sup 3}) and a large (44-151 cm{sup 3}) prostate volume. Results: Patients with large prostates presented with lower urinary bother scores (median 79 vs. 89; p = 0.01) before treatment. Urinary function/bother scores for patients with large prostates decreased significantly compared to patients with small prostates due to irritative/obstructive symptoms only at Time B (pain with urination more than once daily in 48% vs. 18%; p < 0.01). Health-related quality of life did not differ significantly between both patient groups at Times C and D. In contrast to a large prostate, a small initial bladder volume (with associated higher dose-volume load) was predictive for lower urinary bother scores both in the acute and late phase; at Time B it predisposed for pollakiuria but not for pain. Patients with neoadjuvant hormonal therapy reached significantly lower HRQOL scores in several domains (affecting only incontinence in the urinary domain), despite a smaller prostate volume (34 cm{sup 3} vs. 47 cm{sup 3}; p < 0.01). Conclusions: Patients with a large prostate volume have a great risk of irritative/obstructive symptoms (particularly dysuria) in the acute radiotherapy phase. These symptoms recover rapidly and do not influence long-term HRQOL.

  4. Progress and controversies: Radiation therapy for prostate cancer.

    PubMed

    Martin, Neil E; D'Amico, Anthony V

    2014-01-01

    Radiation therapy remains a standard treatment option for men with localized prostate cancer. Alone or in combination with androgen-deprivation therapy, it represents a curative treatment and has been shown to prolong survival in selected populations. In this article, the authors review recent advances in prostate radiation-treatment techniques, photon versus proton radiation, modification of treatment fractionation, and brachytherapy-all focusing on disease control and the impact on morbidity. Also discussed are refinements in the risk stratification of men with prostate cancer and how these are better for matching patients to appropriate treatment, particularly around combined androgen-deprivation therapy. Many of these advances have cost and treatment burden implications, which have significant repercussions given the prevalence of prostate cancer. The discussion includes approaches to improve value and future directions for research. PMID:25234700

  5. Multiparametric magnetic resonance imaging: Current role in prostate cancer management.

    PubMed

    Ueno, Yoshiko; Tamada, Tsutomu; Bist, Vipul; Reinhold, Caroline; Miyake, Hideaki; Tanaka, Utaru; Kitajima, Kazuhiro; Sugimura, Kazuro; Takahashi, Satoru

    2016-07-01

    Digital rectal examination, serum prostate-specific antigen screening and transrectal ultrasound-guided biopsy are conventionally used as screening, diagnostic and surveillance tools for prostate cancer. However, they have limited sensitivity and specificity. In recent years, the role of multiparametric magnetic resonance imaging has steadily grown, and is now part of the standard clinical management in many institutions. In multiparametric magnetic resonance imaging, the morphological assessment of T2-weighted imaging is correlated with diffusion-weighted imaging, dynamic contrast-enhanced imaging perfusion and/or magnetic resonance spectroscopic imaging. Multiparametric magnetic resonance imaging is currently regarded as the most sensitive and specific imaging technique for the evaluation of prostate cancer, including detection, staging, localization and aggressiveness evaluation. This article presents an overview of multiparametric magnetic resonance imaging, and discusses the current role of multiparametric magnetic resonance imaging in the different fields of prostate cancer management. PMID:27184019

  6. Genetically engineered mouse models to study prostate cancer.

    PubMed

    Brzezinska, Elspeth A; Nixon, Colin; Patel, Rachana; Leung, Hing Y

    2015-01-01

    Genetically engineered mouse models have become fundamental tools in the basic and translational research of prostate cancer. There is a plethora of models available to dissect the genetic alterations and aberrant signaling events associated with human prostate cancer and, furthermore, to investigate new and "personalized" therapies to treat the disease. In this chapter, we discuss some of the models recently and currently used to study prostate cancer in vivo, and some considerations when selecting an appropriate model to investigate particular aspects of the disease. We describe the methods required to isolate prostate tumors and conduct basic characterization of the tumor to determine tumor load and histopathology. We also discuss important aspects to be considered when processing samples for further analysis. PMID:25636465

  7. The integrated proactive surveillance system for prostate cancer.

    PubMed

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

    2012-01-01

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

  8. Benign Prostatic Hyperplasia and the Risk of Prostate Cancer and Bladder Cancer: A Meta-Analysis of Observational Studies.

    PubMed

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

    2016-05-01

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

  9. Past exposure to asbestos and combustion products and incidence of cancer among Finnish locomotive drivers.

    PubMed

    Nokso-Koivisto, P; Pukkala, E

    1994-05-01

    Locomotive drivers in the steam engine era were exposed to asbestos during their vocational training for two years while training in workshops. Later in their career they had exposure to coal and diesel combustion products. To assess the level of earlier exposure historical working conditions were reconstructed and hygienic conditions were measured. The average exposure to asbestos (mainly anthophylline) fibres > 5 microns was 5.0 fibres/cm3. Incidence of cancer in a cohort of 8391 members of the Finnish Locomotive Drivers' Association, 1953-91, was analysed. The incidence of lung cancer and also total cancer was below the national average, probably due to the low prevalence of smoking among the drivers in the steam engine era. A four-fold risk of mesothelioma was found, most likely caused by exposure to asbestos. Also the observed 1.5-fold incidence of non-melanoma skin cancer and 1.7-fold risk of cancer of the oral cavity and pharynx may be related to occupation. PMID:8199683

  10. Circulating Levels of 25-hydroxyvitamin D and Prostate Cancer Prognosis

    PubMed Central

    Holt, Sarah K.; Kolb, Suzanne; Fu, Rong; Horst, Ronald; Feng, Ziding; Stanford, Janet L.

    2013-01-01

    Objectives Ecological, in vitro, and in vivo studies demonstrate a link between vitamin D and prostate tumor growth and aggressiveness. The goal of this study was to investigate whether plasma concentration of vitamin D is associated with survivorship and disease progression in men diagnosed with prostate cancer. Methods and Materials We conducted a population-based cohort study of 1,476 prostate cancer patients to assess disease recurrence/progression and prostate cancer-specific mortality (PCSM) risks associated with serum levels of 25(OH) vitamin D [25(OH)D]. Results There were 325 recurrence/progression and 95 PCSM events during an average of 10.8 years of follow-up. Serum levels of 25(OH)D were not associated with risk of recurrence/ progression or mortality. Clinically deficient vitamin D levels were associated with an increased risk of death from other causes. Conclusions We did not find evidence that serum vitamin D levels measured after diagnosis affect prostate cancer prognosis. Lower levels of vitamin D were associated with risk of non-prostate cancer mortality. PMID:23972671

  11. Optoacoustic imaging of an animal model of prostate cancer

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

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

  12. Reduced serum selenoprotein P concentrations in German prostate cancer patients.

    PubMed

    Meyer, Hellmuth-Alexander; Hollenbach, Birgit; Stephan, Carsten; Endermann, Tobias; Morgenthaler, Nils G; Cammann, Henning; Köhrle, Josef; Jung, Klaus; Schomburg, Lutz

    2009-09-01

    Selenium (Se) is essentially needed for the biosynthesis of selenoproteins. Low Se intake causes reduced selenoprotein biosynthesis and constitutes a risk factor for tumorigenesis. Accordingly, some Se supplementation trials have proven effective to reduce prostate cancer risk, especially in poorly supplied individuals. Because Se metabolism is controlled by selenoprotein P (SEPP), we have tested whether circulating SEPP concentrations correlate to prostate cancer stage and grade. A total of 190 men with prostate cancer (n = 90) and "no evidence of malignancy" (NEM; n = 100) histologically confirmed by prostate biopsy were retrospectively analyzed for established tumor markers and for their Se and SEPP status. Prostate specific antigen (PSA), free PSA, total Se, and SEPP concentrations were determined from serum samples and compared with clinicopathologic parameters. The diagnostic performance was analyzed with receiver operating characteristic curves. Median Se and SEPP concentrations differed significantly (P < 0.001) between the groups. Median serum Se concentrations in the 25th to 75th percentile were 95.9 microg/L (82-117.9) in NEM patients and 81.4 microg/L (67.9-98.4) in prostate cancer patients. Corresponding serum SEPP concentrations were 3.4 mg/L (1.9-5.6) in NEM and 2.9 mg/L (1.1-5.5) in prostate cancer patients. The area under the curve (AUC) of a marker combination with age, PSA, and percent free PSA (%fPSA) in combination with the SEPP concentration, yielded the highest diagnostic value (AUC 0.80) compared with the marker combination without SEPP (AUC 0.77) or %fPSA (AUC 0.76). We conclude that decreased SEPP concentration in serum might represent an additional valuable marker for prostate cancer diagnostics. PMID:19690186

  13. A role for STEAP2 in prostate cancer progression.

    PubMed

    Whiteland, Helen; Spencer-Harty, Samantha; Morgan, Claire; Kynaston, Howard; Thomas, David Hywel; Bose, Pradeep; Fenn, Neil; Lewis, Paul; Jenkins, Spencer; Doak, Shareen H

    2014-12-01

    Prostate adenocarcinoma is the second most frequent cancer worldwide and is one of the leading causes of male cancer-related deaths. However, it varies greatly in its behaviour, from indolent non-progressive disease to metastatic cancers with high associated mortality. The aim of this study was to identify predictive biomarkers for patients with localised prostate tumours most likely to progress to aggressive disease, to facilitate future tailored clinical treatment and identify novel therapeutic targets. The expression of 602 genes was profiled using oligoarrays, across three prostate cancer cell lines: CA-HPV-10, LNCaP and PC3, qualitatively identifying several potential prognostic biomarkers. Of particular interest was six transmembrane epithelial antigen of the prostate (STEAP) 1 and STEAP 2 which was subsequently analysed further in prostate cancer tissue samples following optimisation of an RNA extraction method from laser captured cells isolated from formalin-fixed paraffin-embedded biopsy samples. Quantitative analysis of STEAP1 and 2 gene expression were statistically significantly associated with the metastatic cell lines DU145 and PC3 as compared to the normal prostate epithelial cell line, PNT2. This expression pattern was also mirrored at the protein level in the cells. Furthermore, STEAP2 up-regulation was observed within a small patient cohort and was associated with those that had locally advanced disease. Subsequent mechanistic studies in the PNT2 cell line demonstrated that an over-expression of STEAP2 resulted in these normal prostate cells gaining an ability to migrate and invade, suggesting that STEAP2 expression may be a crucial molecule in driving the invasive ability of prostate cancer cells. PMID:25248617

  14. 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

  15. Pathology of prostate cancer and focal therapy ('male lumpectomy').

    PubMed

    Mazzucchelli, Roberta; Scarpelli, Marina; Cheng, Liang; Lopez-Beltran, Antonio; Galosi, Andrea B; Kirkali, Ziya; Montironi, Rodolfo

    2009-12-01

    Focal therapy of the prostate is defined as prostate gland ablation aiming at eradication of unifocal low-risk prostate cancer, and preserving uninvolved (peri-) prostatic tissue and therefore quality of life. The major arguments against focal therapy can be classified under the headings of understaging and multifocality. The argument of understaging highlights the importance of the occasional, but troublesome, finding of a large, extraprostatic or high-grade tumor (Gleason score > or = 7) in about a quarter of radical prostatectomy specimens removed from men initially classified as having a low-risk tumor. Indeed, 85% of all prostate cancer cases are multifocal. These concerns can be offset by additional testing: another biopsy, especially a transperineal mapping biopsy, and magnetic resonance imaging (MRI) of the prostate. The technology needed to ablate small regions or sectors of the prostate harboring a known cancer is rapidly becoming available. Cryotherapy is already being used and the preliminary data are encouraging, Ultrasound-guided high-intensity focused ultrasound (HIFU), photodynamic therapy using newly developed light-sensitizing agents, and MRI-guided HIFU are all promising new tools. PMID:20044631

  16. A possible role of BDNF in prostate cancer detection.

    PubMed

    Bronzetti, E; Artico, M; Forte, F; Pagliarella, G; Felici, L M; D'Ambrosio, A; Vespasiani, G; Bronzetti, B

    2008-04-01

    Many studies have demonstrated that both normal and malignant prostate cells respond to a variety of growth factors, while several significant differences were found between normal and tumoural cells. The aim of this study was to focus on the localization and distribution of the immuno-reactivity for neurotrophins (NTs) and neurotrophin receptors (NTRs) in normal, hyperplastic and prostate cancer cells, obtained from 40 subjects. We studied samples obtained from 16 prostate cancer (PC, retropubic radical prostatectomy), 20 benign prostatic hyperplasia (BPH, supra-pubic prostatectomy) and normal peripheral prostate tissue from four fresh male cadavers. Samples were examined via immunohistochemical techniques in order to detect the expression of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and their own receptors TrkA, p75, TrkB and TrkC. We observed a high expression of BDNF and TrkB in PC and BPH, though no immuno-reactivity was found for p75. Low expression was reported by other NTs and NTRs in the normal peripheral prostate zone, BPH and PC. These data suggest a possible predictive role for NTs and NTRs, especially for BDNF and TrkB, in the diagnosis and/or management of prostate cancer. The absence of p75 expression confirms its supposed role in apoptotic phenomenon. PMID:18357383

  17. Therapeutic efficacy of nanomedicines for prostate cancer: An update

    PubMed Central

    2016-01-01

    Recent advances in cancer nanomedicine have attracted remarkable attention in medical sectors. Pharmacologic research on nanomedicines, including targeted cancer therapy, has increased dramatically in the past 5 years. The success stories of nanomedicines in the clinical field include the fabrication of nanomedicines that show maximum loading efficiency into carriers, maximal release kinetics, and minimum toxicity to healthy cells. Nanoparticle-mediated medicines have been developed to specifically target prostate cancer tissue by use of aptamers, antibody targeting, and sustained release of nanomedicines in a dose- and time-dependent manner. Nanomedicines have been developed for therapeutic application in combination with image-guided therapy in real time. The scope of one of these nanomedicines, Abraxane (paclitaxel), may be extended to prostate cancer therapeutic applications for better quality of patient life and longer survival. This review provides an update on the latest directions and developments in nanomedicines for prostate cancer. PMID:26966723

  18. [Testosterone in the management of metastatic prostate cancer].

    PubMed

    Wolff, J M; Schmid, H P

    2015-11-01

    Background Among all cancer types, prostate cancer (PCa) is the most prevalent cancer and is the third-leading cause of cancer-related death in men. The biologic function of the prostate is decisively influenced by testosterone and its metabolic product dihydrotestosterone. However, there is general uncertainty about the role of testosterone in metastatic castration-resistant prostate cancer (mCRPC). For many years, the androgen hypothesis had been accepted to explain the correlation between testosterone levels and the development or progression of PCa. However, extensive study analyses revealed contradictory results, leading to a reconsideration of the androgen hypothesis. High serum testosterone levels do not predispose to PCa development and low serum testosterone levels are not protective. The importance of testosterone levels in patients with mCRPC has been shown in several registration studies with new drugs, such as abiraterone acetate and enzalutamide. There is growing evidence suggesting a prognostic role of testosterone levels in mCRPC. PMID:26113300

  19. A population-based analysis of clustering identifies a strong genetic contribution to lethal prostate cancer

    PubMed Central

    Nelson, Quentin; Agarwal, Neeraj; Stephenson, Robert; Cannon-Albright, Lisa A.

    2013-01-01

    Background: Prostate cancer is a common and often deadly cancer. Decades of study have yet to identify genes that explain much familial prostate cancer. Traditional linkage analysis of pedigrees has yielded results that are rarely validated. We hypothesize that there are rare segregating variants responsible for high-risk prostate cancer pedigrees, but recognize that within-pedigree heterogeneity is responsible for significant noise that overwhelms signal. Here we introduce a method to identify homogeneous subsets of prostate cancer, based on cancer characteristics, which show the best evidence for an inherited contribution. Methods: We have modified an existing method, the Genealogical Index of Familiality (GIF) used to show evidence for significant familial clustering. The modification allows a test for excess familial clustering of a subset of prostate cancer cases when compared to all prostate cancer cases. Results: Consideration of the familial clustering of eight clinical subsets of prostate cancer cases compared to the expected familial clustering of all prostate cancer cases identified three subsets of prostate cancer cases with evidence for familial clustering significantly in excess of expected. These subsets include prostate cancer cases diagnosed before age 50 years, prostate cancer cases with body mass index (BMI) greater than or equal to 30, and prostate cancer cases for whom prostate cancer contributed to death. Conclusions: This analysis identified several subsets of prostate cancer cases that cluster significantly more than expected when compared to all prostate cancer familial clustering. A focus on high-risk prostate cancer cases or pedigrees with these characteristics will reduce noise and could allow identification of the rare predisposition genes or variants responsible. PMID:23970893

  20. Prognostic DNA Methylation Markers for Prostate Cancer

    PubMed Central

    Strand, Siri H.; Orntoft, Torben F.; Sorensen, Karina D.

    2014-01-01

    Prostate cancer (PC) is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181) and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC. PMID:25238417

  1. When prostate cancer remains undetectable: The dilemma.

    PubMed

    Mustafa, Mahmoud Othman; Pisters, Louis

    2015-03-01

    Since the first report on the efficacy of sextant biopsy under transrectal ultrasound guidance, there have been many modifications related to the total number of cores and the localization of biopsies to improve the prostate cancer (PCa) detection rate. The 2010 National Comprehensive Cancer Network Early PCa Detection Guidelines noted the 12-core biopsy scheme as the standard. However, this extended biopsy scheme still fails to detect 20% of high-grade PCa that can be detected by detailed pathological evaluation of radical prostatectomy; therefore, there is need for saturation biopsies. The existence of suspicions of PCa after previous negative biopsy or biopsies represents a valid indication for saturation biopsy. There has been no significant increment in morbidity or in insignificant PCa detection rates when a saturation biopsy scheme was used with an extended biopsy scheme. Along with the improvement in the PCa detection rate, accurate oncological mapping of PCa is another important consideration of saturation biopsies. The ideal number of cores and the diagnostic value of saturation biopsy after the failure of initial therapy are some of the issues that need to be addressed. Preliminary reports have shown that magnetic resonance imaging can improve the PCa detection rate, save patients from unnecessary biopsies, and decrease the need for a high number of cores; however, multiple limitations continue to exist. PMID:26328196

  2. Prognostic DNA methylation markers for prostate cancer.

    PubMed

    Strand, Siri H; Orntoft, Torben F; Sorensen, Karina D

    2014-01-01

    Prostate cancer (PC) is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181) and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC. PMID:25238417

  3. Segmentation of prostate cancer tissue microarray images

    NASA Astrophysics Data System (ADS)

    Cline, Harvey E.; Can, Ali; Padfield, Dirk

    2006-02-01

    Prostate cancer is diagnosed by histopathology interpretation of hematoxylin and eosin (H and E)-stained tissue sections. Gland and nuclei distributions vary with the disease grade. The morphological features vary with the advance of cancer where the epithelial regions grow into the stroma. An efficient pathology slide image analysis method involved using a tissue microarray with known disease stages. Digital 24-bit RGB images were acquired for each tissue element on the slide with both 10X and 40X objectives. Initial segmentation at low magnification was accomplished using prior spectral characteristics from a training tissue set composed of four tissue clusters; namely, glands, epithelia, stroma and nuclei. The segmentation method was automated by using the training RGB values as an initial guess and iterating the averaging process 10 times to find the four cluster centers. Labels were assigned to the nearest cluster center in red-blue spectral feature space. An automatic threshold algorithm separated the glands from the tissue. A visual pseudo color representation of 60 segmented tissue microarray image was generated where white, pink, red, blue colors represent glands, epithelia, stroma and nuclei, respectively. The higher magnification images provided refined nuclei morphology. The nuclei were detected with a RGB color space principle component analysis that resulted in a grey scale image. The shape metrics such as compactness, elongation, minimum and maximum diameters were calculated based on the eigenvalues of the best-fitting ellipses to the nuclei.

  4. Nuclear morphometry, nucleomics and prostate cancer progression

    PubMed Central

    Veltri, Robert W; Christudass, Christhunesa S; Isharwal, Sumit

    2012-01-01

    Prostate cancer (PCa) results from a multistep process. This process includes initiation, which occurs through various aging events and multiple insults (such as chronic infection, inflammation and genetic instability through reactive oxygen species causing DNA double-strand breaks), followed by a multistep process of progression. These steps include several genetic and epigenetic alterations, as well as alterations to the chromatin structure, which occur in response to the carcinogenic stress-related events that sustain proliferative signaling. Events such as evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis are readily observed. In addition, in conjunction with these critical drivers of carcinogenesis, other factors related to the etiopathogenesis of PCa, involving energy metabolism and evasion of the immune surveillance system, appear to be involved. In addition, when cancer spread and metastasis occur, the ‘tumor microenvironment' in the bone of PCa patients may provide a way to sustain dormancy or senescence and eventually establish a ‘seed and soil' site where PCa proliferation and growth may occur over time. When PCa is initiated and progression ensues, significant alterations in nuclear size, shape and heterochromatin (DNA transcription) organization are found, and key nuclear transcriptional and structural proteins, as well as multiple nuclear bodies can lead to precancerous and malignant changes. These series of cellular and tissue-related malignancy-associated events can be quantified to assess disease progression and management. PMID:22504875

  5. 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

  6. 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

  7. Breast and Prostate Cancer and Hormone-Related Gene Variant Study

    Cancer.gov

    The Breast and Prostate Cancer and Hormone-Related Gene Variant Study allows large-scale analyses of breast and prostate cancer risk in relation to genetic polymorphisms and gene-environment interactions that affect hormone metabolism.

  8. High-Dose Radiation May Be No Better for Low-Risk Prostate Cancer

    MedlinePlus

    ... Radiation May Be No Better for Low-Risk Prostate Cancer Study finds no benefits in disease progression, survival ... doses of radiation may not benefit low-risk prostate cancer patients, a new review suggests. "In the field ...

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

    MedlinePlus

    ... News » Filed under: Prostate Cancer Study: Cialis (Tadalafil) Does Not Prevent Erectile Dysfunction in Prostate Cancer Patients ... States and Canada have found that Cialis (tadalafil) does not help men avoid erectile dysfunction after radiation ...

  10. 'Active Surveillance' of Prostate Cancer Doesn't Dampen Quality of Life

    MedlinePlus

    ... Active Surveillance' of Prostate Cancer Doesn't Dampen Quality of Life Choosing no treatment and regular check- ... with low-risk prostate cancer report a good quality of life after choosing active surveillance as a ...

  11. Survivin Is a Potential Mediator of Prostate Cancer Metastasis

    SciTech Connect

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

    2010-11-15

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

  12. Prostate-specific membrane antigen protein expression in tumor tissue and risk of lethal prostate cancer

    PubMed Central

    Kasperzyk, Julie L.; Finn, Stephen P.; Flavin, Richard; Fiorentino, Michelangelo; Lis, Rosina; Hendrickson, Whitney K.; Clinton, Steven K.; Sesso, Howard D.; Giovannucci, Edward L.; Stampfer, Meir J.; Loda, Massimo; Mucci, Lorelei A.

    2013-01-01

    Background Over-expression of prostate-specific membrane antigen (PSMA) in tumor tissue and serum has been linked to increased risk of biochemical recurrence in surgically treated prostate cancer patients, but no studies have assessed its association with disease-specific mortality. Methods We examined whether high PSMA protein expression in prostate tumor tissue was associated with lethal disease, and with tumor biomarkers of progression, among participants of two US-based cohorts (n=902, diagnosed 1983–2004). We used Cox proportional hazards regression to calculate multivariable hazard ratios (HR) and 95% confidence intervals (CI) of lethal prostate cancer, defined as disease-specific death or development of distant metastases (n=95). Partial Spearman rank correlation coefficients were used to correlate PSMA with tumor biomarkers. Results During an average 13 years of follow-up, higher PSMA expression at prostatectomy was significantly associated with lethal prostate cancer (age-adjusted HRQuartile(Q)4vs.Q1=2.42; p-trend<0.01). This association was attenuated and non-significant (multivariable-adjusted HRQ4vs.Q1=1.01; p-trend=0.52) after further adjusting for Gleason score and PSA at diagnosis. High PSMA expression was significantly (p<0.05) correlated with higher Gleason score and PSA at diagnosis, increased tumor angiogenesis, lower vitamin D receptor and androgen receptor expression, and absence of ERG expression. Conclusions High tumor PSMA expression was not an independent predictor of lethal prostate cancer in the current study. PSMA expression likely captures, in part, malignant features of Gleason grade and tumor angiogenesis. Impact PSMA is not a strong candidate biomarker for predicting prostate cancer-specific mortality in surgically treated patients. PMID:24130224

  13. Multimodal and three-dimensional imaging of prostate cancer.

    PubMed

    Lee, Zhenghong; Sodee, D Bruce; Resnick, Martin; Maclennan, Gregory T

    2005-09-01

    Accurate characterization of prostate cancer is crucial for treatment planning and patient management. Non-invasive SPECT imaging using a radiolabeled monoclonal antibody, 111In-labeled capromab pendetide, offers advantage over existing means for prostate cancer diagnosis and staging. However, there are difficulties associated with the interpretation of these SPECT images. In this study, we developed a 3D surface-volume hybrid rendering method that utilizes multi-modality image data to facilitate diagnosis of prostate cancer. SPECT and CT or MRI (or both) images were aligned either manually or automatically. 3D hybrid rendering was implemented to blend prostate tumor distribution from SPECT in pelvis with anatomic structures from CT/MRI. Feature extraction technique was also implemented within the hybrid rendering for tumor uptake enhancement. Autoradiographic imaging and histological evaluation were performed to correlate with the in-vivo SPECT images. Warping registration of histological sections was carried out to compensate the deformation of histology slices during fixation to help the alignment between histology and in-vivo images. Overall, the rendered volumetric evaluation of prostate cancer has the potential to greatly increase the confidence in the reading of radiolabeled monoclonal antibody scans, especially in patients where there is a high suspicion of prostate tumor metastasis. PMID:15893911

  14. LHRH-Conjugated Lytic Peptides Directly Target Prostate Cancer Cells

    PubMed Central

    Yates, Clayton; Sharp, Starlette; Jones, Jacqueline; Topps, Daphne; Coleman, Mathew; Aneja, Ritu; Jaynes, Jesse; Turner, Timothy

    2010-01-01

    Prostate cancer is the second leading cause of cancer deaths among men. For patients with hormone-refractory disease, few treatments are available once the tumor has metastasized beyond the prostate. In the present study, two conjugated lytic peptide sequences (named JCHLHRH and JC21LHRH) were designed to target luteinizing hormone-releasing hormone receptors (LHRH-R). Our results indicate that human prostate cancer cell lines were sensitive to both LHRH-conjugated and non-conjugated lytic peptides, with IC50 concentrations for LNCaP cells, 4.4 and 9.1 µM; for DU-145 cells, 4.8 and 5.7 µM; and for PC-3 cells, 4.4 and 8.2 µM, respectively. JCHLHRH and JC21LHRH were nontoxic to normal primary human prostate epithelial cells or to bone marrow stromal cells in co-culture. There were morphological changes in PC-3 cells after 3 hr of exposure to either peptide; after 6 hr, there were significant reductions in cell numbers. Exposure of PC-3 cells for 24 hr to either JCHLHRH or JC21LHRH blocked their growth over 3 days. Since JCHLHRH and JC21LHRH have specificity for and anti-proliferative activity against tumor cells, and low toxicity for normal prostate cells, these peptides could serve as a new type of therapy for prostate cancer. PMID:20869347

  15. Current role of multiparametric magnetic resonance imaging for prostate cancer

    PubMed Central

    Chevallier, Olivier; Moulin, Morgan; Favelier, Sylvain; Genson, Pierre-Yves; Pottecher, Pierre; Crehange, Gilles; Cochet, Alexandre; Cormier, Luc

    2015-01-01

    Multiparametric magnetic resonance imaging (mp-MRI) has shown promising results in diagnosis, localization, risk stratification and staging of clinically significant prostate cancer, and targeting or guiding prostate biopsy. mp-MRI consists of T2-weighted imaging (T2WI) combined with several functional sequences including diffusion-weighted imaging (DWI), perfusion or dynamic contrast-enhanced imaging (DCEI) and spectroscopic imaging. Recently, mp-MRI has been used to assess prostate cancer aggressiveness and to identify anteriorly located tumors before and during active surveillance. Moreover, recent studies have reported that mp-MRI is a reliable imaging modality for detecting local recurrence after radical prostatectomy or external beam radiation therapy. Because assessment on mp-MRI can be subjective, use of the newly developed standardized reporting Prostate Imaging and Reporting Archiving Data System (PI-RADS) scoring system and education of specialist radiologists are essential for accurate interpretation. This review focuses on the current place of mp-MRI in prostate cancer and its evolving role in the management of prostate cancer. PMID:26682144

  16. Prostate-specific extracellular vesicles as a novel biomarker in human prostate cancer.

    PubMed

    Park, Yong Hyun; Shin, Hyun Woo; Jung, Ae Ryang; Kwon, Oh Sung; Choi, Yeong-Jin; Park, Jaesung; Lee, Ji Youl

    2016-01-01

    Extracellular vesicles (EVs) may play an important role in cancer development and progression. We aimed to investigate the prognostic potential of prostate-specific EVs in prostate cancer (PCa) patients. Plasma and prostate tissue were collected from patients who underwent surgery for PCa (n = 82) or benign prostatic hyperplasia (BPH, n = 28). To analyze the quantity of EVs in prostate, we performed transmission electron microscopy (TEM), immuno-TEM with CD63 and prostate-specific membrane antigen (PSMA), and immunofluorescence staining. After EV isolation from plasma, CD63 and PSMA concentration was measured using ELISA kits. PSMA-positive areas in prostate differed in patients with BPH, and low-, intermediate-, and high-risk PCa (2.4, 8.2, 17.5, 26.5%, p < 0.001). Plasma PSMA-positive EV concentration differed in patients with BPH, and low-, intermediate-, and high-risk PCa (21.9, 43.4, 49.2, 59.9 ng/mL, p < 0.001), and ROC curve analysis indicated that plasma PSMA-positive EV concentration differentiated PCa from BPH (AUC 0.943). Patients with lower plasma PSMA-positive EV concentration had greater prostate volume (50.2 vs. 33.4 cc, p < 0.001) and lower pathologic Gleason score (p = 0.025). During the median follow-up of 18 months, patients with lower plasma PSMA-positive EV concentration tended to have a lower risk of biochemical failure than those with higher levels of prostate-specific EVs (p = 0.085). PMID:27503267

  17. Prostate-specific extracellular vesicles as a novel biomarker in human prostate cancer

    PubMed Central

    Park, Yong Hyun; Shin, Hyun Woo; Jung, Ae Ryang; Kwon, Oh Sung; Choi, Yeong-Jin; Park, Jaesung; Lee, Ji Youl

    2016-01-01

    Extracellular vesicles (EVs) may play an important role in cancer development and progression. We aimed to investigate the prognostic potential of prostate-specific EVs in prostate cancer (PCa) patients. Plasma and prostate tissue were collected from patients who underwent surgery for PCa (n = 82) or benign prostatic hyperplasia (BPH, n = 28). To analyze the quantity of EVs in prostate, we performed transmission electron microscopy (TEM), immuno-TEM with CD63 and prostate-specific membrane antigen (PSMA), and immunofluorescence staining. After EV isolation from plasma, CD63 and PSMA concentration was measured using ELISA kits. PSMA-positive areas in prostate differed in patients with BPH, and low-, intermediate-, and high-risk PCa (2.4, 8.2, 17.5, 26.5%, p < 0.001). Plasma PSMA-positive EV concentration differed in patients with BPH, and low-, intermediate-, and high-risk PCa (21.9, 43.4, 49.2, 59.9 ng/mL, p < 0.001), and ROC curve analysis indicated that plasma PSMA-positive EV concentration differentiated PCa from BPH (AUC 0.943). Patients with lower plasma PSMA-positive EV concentration had greater prostate volume (50.2 vs. 33.4 cc, p < 0.001) and lower pathologic Gleason score (p = 0.025). During the median follow-up of 18 months, patients with lower plasma PSMA-positive EV concentration tended to have a lower risk of biochemical failure than those with higher levels of prostate-specific EVs (p = 0.085). PMID:27503267

  18. Update on prostate cancer in black men within the UK

    PubMed Central

    Jones, Abeyna LC; Chinegwundoh, Frank

    2014-01-01

    There is a wealth of evidence which can be traced back to the African transatlantic slave trade indicating that black men have a higher risk of prostate cancer compared to other ethnic groups. Migration to Westernised countries may have had little effect on the incidence of prostate cancer in this ethnic group; however, current evidence indicates that there are several complex factors that may contribute to this risk. Studies in the UK quote that black men are at 2–3 times the risk of prostate cancer in comparison to their Caucasian counterparts, with a 30% higher mortality rate. Caution should be taken prior to the interpretation of these results due to a paucity of research in this area, limited accurate ethnicity data, and lack of age-specific standardisation for comparison. Cultural attitudes towards prostate cancer and health care in general may have a significant impact on these figures, combined with other clinico-pathological associations. This update summarises new contributory research on this subject, highlighting the need to increase awareness and understanding of prostate cancer amongst high-risk communities and to support further robust research in this area by nominating a lead in cancer and ethnicity studies within the National Health Service. PMID:25228911

  19. Abnormal expression of CDK11p58 in prostate cancer

    PubMed Central

    2014-01-01

    Background CDK11p58 is one of the large families of p34cdc2-related kinases whose functions are linked with cell cycle progression, tumorigenesis and apoptotic signaling. Our previous investigation demonstrated that CDK11p58 repressed androgen receptor (AR) transcriptional activity and was involved in the negative regulation of AR function. Methods CDK11p58 expression was examined in the prostate cancer tissues and adjacent tissues by IHC and qRT-PCR. Cell apoptosis was detected by flow cytometry. The metastasis of cancer cells was evaluated by the Transwell Assay. Finally we further investigated the underlying molecular mechanisms by examining expression levels of relevant proteins using western blot analysis. Results We found that both RNA and protein expression of CDK11p58 were low in prostate cancer tissues compared with its adjacent noncancerous tissues. CDK11p58 promoted the prostate cancer cell apoptosis and inhibited its metastasis in a kinase dependent way. And finally CDK11p58 could inhibit the metastasis of AR positive prostate cancer cells through inhibition of integrin β3 and MMP2. Conclusions These data indicate that CDK11p58 is an anti-metastasis gene product in prostate cancer. PMID:24397471

  20. Primary versus castration-resistant prostate cancer: modeling through novel murine prostate cancer cell lines.

    PubMed

    Daoud, Georges; Monzer, Alissar; Bahmad, Hisham; Chamaa, Farah; Hamdar, Layal; Mouhieddine, Tarek H; Shayya, Sami; Eid, Assaad; Kobeissy, Firas; Liu, Yen-Nien; Abou-Kheir, Wassim

    2016-05-17

    Cell lines representing the progression of prostate cancer (PC) from an androgen-dependent to an androgen-independent state are scarce. In this study, we used previously characterized prostate luminal epithelial cell line (Plum), under androgen influence, to establish cellular models of PC progression. Cells derived from orthotopic tumors have been isolated to develop an androgen-dependent (PLum-AD) versus an androgen-independent (PLum-AI) model. Upon immunofluorescent, qRT-PCR and Western blot analyses, PLum-AD cells mostly expressed prostate epithelial markers while PLum-AI cells expressed mesenchymal cell markers. Interestingly, both cell lines maintained a population of stem/progenitor cells. Furthermore, our data suggest that both cell lines are tumorigenic; PLum-AD resulted in an adenocarcinoma whereas PLum-AI resulted in a sarcomatoid carcinoma when transplanted subcutaneously in NOD-SCID mice. Finally, gene expression profiles showed enrichment in functions involved in cell migration, apoptosis, as well as neoplasm invasiveness and metastasis in PLum-AI cells. In conclusion, these data suggest that the newly isolated cell lines represent a new in vitro model of androgen-dependent and -independent PC. PMID:27036046