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Sample records for intermittent androgen deprivation

  1. Continuous vs. intermittent androgen deprivation therapy for metastatic prostate cancer

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    Langenhuijsen, J.F.; Badhauser, D.; Schaaf, B.; Kiemeney, L.A.L.M.; Witjes, J.A.; Mulders, P.F.A.

    2013-01-01

    OBJECTIVES: To analyze the predictive value of PSA for progression and the role of testosterone for quality of life (QOL) in patients with androgen deprivation therapy (ADT) for metastatic prostate cancer. MATERIALS AND METHODS: PSA and testosterone data were used from a phase III trial randomizing

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

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

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

  3. Metabolic syndrome in patients with prostate cancer undergoing intermittent androgen-deprivation therapy.

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    Rezaei, Mohammadali Mohammadzadeh; Rezaei, Mohammadhadi Mohammadzadeh; Ghoreifi, Alireza; Kerigh, Behzad Feyzzadeh

    2016-01-01

    The presence of metabolic syndrome in men with prostate cancer (PCa) undergoing androgen-deprivation therapy (ADT), especially intermittent type, has not been completely evaluated. The aim of this study is to evaluate metabolic syndrome in men with PCa undergoing intermittent ADT. In this longitudinal study, we studied the prevalence of metabolic syndrome and its components in 190 patients who were undergoing intermittent ADT. The metabolic syndrome was defined according to the Adult Treatment Panel III criteria. All metabolic parameters, including lipid profile, blood glucose, blood pressures, and waist circumferences of the patients were measured six and 12 months after treatment. Mean age of the patients was 67.5 ± 6.74 years. The incidence of metabolic syndrome after six and 12 months was 6.8% and 14.7%, respectively. Analysis of various components of the metabolic syndrome revealed that patients had significantly higher overall prevalence of hyperglycemia, abdominal obesity, and hypertriglyceridemia in their six- and 12-month followups, but blood pressure has not been changed in the same period except for diastolic blood pressure after six months. Although there was an increased risk of metabolic syndrome in patients receiving intermittent ADT, it was lower than other studies that treated the same patients with continuous ADT. Also it seems that intermittent ADT has less metabolic complications than continuous ADT and could be used as a safe alternative in patients with advanced and metastatic PCa.

  4. Intermittent androgen deprivation therapy in patients with prostate cancer: Connecting the dots

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    Per-Anders Abrahamsson

    2017-10-01

    Full Text Available Intermittent androgen deprivation therapy (IADT is now being increasingly opted by the treating physicians and patients with prostate cancer. The most common reason driving this is the availability of an off-treatment period to the patients that provides some relief from treatment-related side-effects, and reduced treatment costs. IADT may also delay the progression to castration-resistant prostate cancer. However, the use of IADT in the setting of prostate cancer has not been strongly substantiated by data from clinical trials. Multiple factors seem to contribute towards this inadequacy of supportive data for the use of IADT in patients with prostate cancer, e.g., population characteristics (both demographic and clinical, study design, treatment regimen, on- and off-treatment criteria, duration of active treatment, endpoints, and analysis. The present review article focuses on seven clinical trials that evaluated the efficacy of IADT vs. continuous androgen deprivation therapy for the treatment of prostate cancer. The results from these clinical trials have been discussed in light of the factors that may impact the treatment outcomes, especially the disease (tumor burden. Based on evidence, potential candidate population for IADT has been suggested along with recommendations for the use of IADT in patients with prostate cancer.

  5. Hedgehog/Gli supports androgen signaling in androgen deprived and androgen independent prostate cancer cells

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    Shtutman Michael

    2010-04-01

    Full Text Available Abstract Background Castration resistant prostate cancer (CRPC develops as a consequence of hormone therapies used to deplete androgens in advanced prostate cancer patients. CRPC cells are able to grow in a low androgen environment and this is associated with anomalous activity of their endogenous androgen receptor (AR despite the low systemic androgen levels in the patients. Therefore, the reactivated tumor cell androgen signaling pathway is thought to provide a target for control of CRPC. Previously, we reported that Hedgehog (Hh signaling was conditionally activated by androgen deprivation in androgen sensitive prostate cancer cells and here we studied the potential for cross-talk between Hh and androgen signaling activities in androgen deprived and androgen independent (AI prostate cancer cells. Results Treatment of a variety of androgen-deprived or AI prostate cancer cells with the Hh inhibitor, cyclopamine, resulted in dose-dependent modulation of the expression of genes that are regulated by androgen. The effect of cyclopamine on endogenous androgen-regulated gene expression in androgen deprived and AI prostate cancer cells was consistent with the suppressive effects of cyclopamine on the expression of a reporter gene (luciferase from two different androgen-dependent promoters. Similarly, reduction of smoothened (Smo expression with siRNA co-suppressed expression of androgen-inducible KLK2 and KLK3 in androgen deprived cells without affecting the expression of androgen receptor (AR mRNA or protein. Cyclopamine also prevented the outgrowth of AI cells from androgen growth-dependent parental LNCaP cells and suppressed the growth of an overt AI-LNCaP variant whereas supplemental androgen (R1881 restored growth to the AI cells in the presence of cyclopamine. Conversely, overexpression of Gli1 or Gli2 in LNCaP cells enhanced AR-specific gene expression in the absence of androgen. Overexpressed Gli1/Gli2 also enabled parental LNCaP cells to

  6. Androgen deprivation treatment of sexual behavior.

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    Houts, Frederick W; Taller, Inna; Tucker, Douglas E; Berlin, Fred S

    2011-01-01

    Gonadotropin-releasing hormone agonists are underutilized in patients seeking diminution of problematic sexual drives. This chapter reviews the literature on surgical castration of sex offenders, anti-androgen use and the rationale for providing androgen deprivation therapy, rather than selective serotonin reuptake inhibitors or more conservative interventions, for patients with paraphilias and excessive sexual drive. Discussions of informed consent, side effects, contraindications and case examples are provided. Copyright © 2011 S. Karger AG, Basel.

  7. Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

    National Research Council Canada - National Science Library

    Wang, Zhou

    2003-01-01

    .... Intermittent androgen ablation therapy may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells...

  8. Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

    National Research Council Canada - National Science Library

    Wang, Zhou

    2005-01-01

    .... Intermittent androgen ablation therapy may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells...

  9. Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

    National Research Council Canada - National Science Library

    Wang, Zhou

    2006-01-01

    .... Intermittent androgen ablation therapy (IAAT) may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells...

  10. Enhancement of Intermittent Androgen Ablation Therapy by Finasteride Administration in Animal Models

    National Research Council Canada - National Science Library

    Wang, Zhou

    2004-01-01

    .... Intermittent androgen ablation therapy may slow down the development of androgen refractory tumors because intermittent recovery of androgens can induce differentiation of prostatic epithelial cells...

  11. Androgen deprivation therapy-associated vasomotor symptoms

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    Jones, Jason M; Kohli, Manish; Loprinzi, Charles L

    2012-01-01

    Androgen deprivation therapy (ADT) is widely used as standard therapy in the treatment of locally advanced and metastatic prostate cancer. While efficacious, ADT is associated with multiple side effects, including decreased libido, erectile dysfunction, diabetes, loss of muscle tone and altered body composition, osteoporosis, lipid changes, memory loss, gynecomastia and hot flashes. The breadth of literature for the treatment of hot flashes is much smaller in men than that in women. While hor...

  12. Mathematical modeling of continuous and intermittent androgen suppression for the treatment of advanced prostate cancer.

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    Voth, Alacia M; Alford, John G; Swim, Edward W

    2017-06-01

    Prostate cancer is one of the most prevalent types of cancer among men. It is stimulated by the androgens, or male sexual hormones, which circulate in the blood and diffuse into the tissue where they stimulate the prostate tumor to grow. One of the most important treatments for advanced prostate cancer has become androgen deprivation therapy (ADT). In this paper we present three different models of ADT for prostate cancer: continuous androgen suppression (CAS), intermittent androgen suppression (IAS), and periodic androgen suppression. Currently, many patients in the U.S. receive CAS therapy of ADT, but many undergo a relapse after several years and experience adverse side effects while receiving treatment. Some clinical studies have introduced various IAS regimens in order to delay the time to relapse, and/or to reduce the economic costs and adverse side effects. We will compute and analyze parameter sensitivity analysis for CAS and IAS which may give insight to plan effective data collection in a future clinical trial. Moreover, a periodic model for IAS is used to develop an analytical formulation for relapse times which then provides information about the sensitivity of relapse to the parameters in our models.

  13. Mathematical Models of Androgen Resistance in Prostate Cancer Patients under Intermittent Androgen Suppression Therapy

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    Javier Baez

    2016-11-01

    Full Text Available Predicting the timing of a castrate resistant prostate cancer is critical to lowering medical costs and improving the quality of life of advanced prostate cancer patients. We formulate, compare and analyze two mathematical models that aim to forecast future levels of prostate-specific antigen (PSA. We accomplish these tasks by employing clinical data of locally advanced prostate cancer patients undergoing androgen deprivation therapy (ADT. While these models are simplifications of a previously published model, they fit data with similar accuracy and improve forecasting results. Both models describe the progression of androgen resistance. Although Model 1 is simpler than the more realistic Model 2, it can fit clinical data to a greater precision. However, we found that Model 2 can forecast future PSA levels more accurately. These findings suggest that including more realistic mechanisms of androgen dynamics in a two population model may help androgen resistance timing prediction.

  14. Clinical Outcomes and Testosterone Levels Following Continuous Androgen Deprivation in Patients with Relapsing or Locally Advanced Prostate Cancer: A Post Hoc Analysis of the ICELAND Study.

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    Tombal, Bertrand; Cornel, Erik B; Persad, Raj; Stari, Anny; Gómez Veiga, Francisco; Schulman, Claude

    2017-11-01

    Lower serum testosterone levels correlate with improved cause specific survival and longer time to progression in year 1 of continuous androgen deprivation in men with prostate cancer. ICELAND was a large European study demonstrating the efficacy of leuprorelin (Eligard®) during continuous androgen deprivation. In this post hoc analysis we investigated serum testosterone levels within year 1 of continuous androgen deprivation to determine survival and time to progression. In ICELAND (ClinicalTrials.gov NCT00378690) patients with locally advanced or relapsing nonmetastatic prostate cancer and with prostate specific antigen 1 ng/ml or less following 6-month induction with leuprorelin 3-month depot 22.5 mg (plus bicalutamide 50 mg per day for 1 month) were randomized 1:1 to continuous androgen deprivation (361) or intermittent androgen deprivation (340) with leuprorelin for 36 months. Patients receiving continuous androgen deprivation were stratified by minimum, median and maximum testosterone levels during year 1 of therapy into 20 or less, greater than 20 to 50 and greater than 50 ng/dl subgroups. Cause specific survival and time to prostate specific antigen (castrate resistant prostate cancer) progression were analyzed. A total of 90.1%, 83.5% and 74.5% of patients receiving continuous androgen deprivation achieved minimum, median and maximum serum testosterone levels of 20 ng/dl or less, respectively. Cause specific survival rates and time to prostate specific antigen progression did not differ among the testosterone subgroups. In patients receiving continuous androgen deprivation cause specific survival and time to prostate specific antigen progression did not differ according to testosterone levels in year 1 of therapy. This finding may in part be due to the induction period and the effectiveness of leuprorelin in lowering testosterone. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  15. Androgen deprivation therapy (castration therapy) and pedophilia: What's new.

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    Silvani, Mauro; Mondaini, Nicola; Zucchi, Alessandro

    2015-09-30

    Andrology is a constantly evolving discipline, embracing social problems like pedophilia and its pharmacological treatment. With regard to chemical castration, the andrologist may perform an important role as part of a team of specialists. At present, no knowledge is available regarding hormonal, chromosomal or genetic alterations involved in pedophilia. International legislation primarily aims to defend childhood, but does not provide for compulsory treatment. We reviewed international literature that, at present, only comprises a few reports on research concerning androgen deprivation. Most of these refer to the use of leuprolide acetate, rather than medroxyprogesterone and cyproterone acetate, which present a larger number of side effects. Current opinions on chemical castration for pedophilia are discordant. Some surveys confirm that therapy reduces sexual thoughts and fantasies, especially in recidivism. On the other hand, some authors report that chemical castration does not modify the pedophile's personality. In our opinion, once existing legislation has changed, andrologists could play a significant role in the selection of patients to receive androgen deprivation therapy, due in part to their knowledge about its action and side effects.

  16. Metabolic sequelae associated with androgen deprivation therapy for prostate cancer.

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    Faris, Jason E; Smith, Matthew R

    2010-06-01

    To summarize the metabolic alterations associated with androgen deprivation therapy (ADT) for prostate cancer and to evaluate the evidence linking ADT with an increased risk of diabetes and cardiovascular disease. ADT by either bilateral orchiectomy or treatment with gonadotropin-releasing hormone agonists causes changes in body composition, alterations in lipid profiles, and decreased insulin sensitivity. The spectrum of metabolic changes during ADT is distinct from classically described metabolic syndrome. Population-based, linked cancer registry studies have consistently reported significant associations between ADT and greater risk for diabetes mellitus. Some but not all studies have reported a link between ADT and cardiovascular disease risk. Most studies have reported no increase in cardiovascular mortality following ADT. ADT appears causally associated with diabetes mellitus. ADT is also linked to cardiovascular morbidity, although there is less evidence that this relationship is causal.

  17. Radiation therapy and androgen deprivation in the management of high risk prostate cancer

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    Dal Pra, Alan; Cury, Fabio L.; Souhami, Luis, E-mail: luis.souhami@muhc.mcgill.c [McGill University Health Centre, Montreal, QC (Canada). Dept. of Oncology. Division of Radiation Oncology

    2011-03-15

    The combined use of radiation therapy (RT) and androgen deprivation for patients with localized high-risk prostate cancer is commonly accepted as the standard treatment among uro-oncologists. Preclinical studies have provided rationale for the use of this combination. Additionally, results of phase 3 studies using conventional doses of RT have supported the combined approach. Other phase 3 studies have also shown a benefit for using higher doses of RT; however, the role of androgen deprivation in this context is not clear. The optimal duration of the androgen deprivation, in both the neoadjuvant and adjuvant setting, is still under investigation. This article critically reviews the data on the use of RT combined with androgen deprivation for the treatment of high-risk prostate cancer with emphasis on the results of phase 3 trials. (author)

  18. Prostate Cancer Metastases to Bone: Role of High Bone Turnover Induced by Androgen Deprivation

    National Research Council Canada - National Science Library

    Padalecki, Susan

    2002-01-01

    .... Treatment with androgen deprivation therapy leads to an increase in bone turnover as indicated by the loss of bone mineral density and the increase in markers of bone turnover in patients on treatment...

  19. Radiation therapy and androgen deprivation in the management of high risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Alan Dal Pra

    2011-04-01

    Full Text Available The combined use of radiation therapy (RT and androgen deprivation for patients with localized high-risk prostate cancer is commonly accepted as the standard treatment among uro-oncologists. Preclinical studies have provided rationale for the use of this combination. Additionally, results of phase 3 studies using conventional doses of RT have supported the combined approach. Other phase 3 studies have also shown a benefit for using higher doses of RT; however, the role of androgen deprivation in this context is not clear. The optimal duration of the androgen deprivation, in both the neoadjuvant and adjuvant setting, is still under investigation. This article critically reviews the data on the use of RT combined with androgen deprivation for the treatment of high-risk prostate cancer with emphasis on the results of phase 3 trials.

  20. Maintaining intimacy for prostate cancer patients on androgen deprivation therapy.

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    Wassersug, Richard J

    2016-03-01

    Androgen deprivation therapy (ADT) causes erectile dysfunction and increases patients' emotionality while diminishing their sexual interest. ADT has been linked to erosion of spousal bonds; however, this is not an invariant outcome. Understanding the factors that lead to these various outcomes may help couples deal with ADT. A subset of couples report that they became closer as a result of the patients going on ADT. Recent data suggest that what helps couples most is preemptive awareness of ADT's side-effects and congruence in how patients and their partners understand and accept the psychosexual impact of ADT. Sex therapy for prostate cancer patients divides along gendered lines, with distinctly 'male' (recovery of erections) and 'female' (promoting sexual practices that are not erection dependent) approaches. Unfortunately, neither is very effective for couples when the patient is on ADT. Options beyond the standard gendered framework, such as use of an external penile prosthesis, may be worth offering to ADT patients trying to find a 'new normal' that is sexually rewarding for them. Intimacy is sharing something with someone that one shares with no one else. Exploring novel sexual practices can help couples stay intimate, even when the patient is on ADT.

  1. Biopsychosocial impact of prostate cancer and androgen-deprivation therapy.

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    Tripp, Dean A; Verreault, Phylicia; Tong, Steven; Izard, Jason; Black, Angela; Siemens, D Robert

    2017-10-01

    Prostate cancer is the most non-cutaneous malignancy in men, and androgen-deprivation therapy (ADT) is a cornerstone of management in advanced disease. The aim of this study was to evaluate the association of ADT with changes in depression and mental and physical quality of life (QoL) within a prospective patient cohort design. Patients were prospectively recruited and consented at a single academic health sciences centre in Ontario, Canada. Inclusion criteria included those men with adenocarcinoma of the prostate and either on watchful waiting or initiating ADT as palliation or as an adjuvant therapy for high-risk localized disease. All three cohorts were followed in routine care and completed psychosocial evaluations, including depression, social support, anxiety, and QoL measures. In comparison to the control cohort of patients with prostate cancer on watchful waiting, initiation of ADT over a two-year period of time was not associated with any changes in depression or mental QoL. Instead, all patients, regardless of treatment cohort, showed increased depression scores and reduced mental QoL scores over time; however, for patients receiving ADT, a significant reduction in physical QoL compared to patients who did not receive ADT was demonstrated. ADT does not appear to significantly impact depressive symptoms and mental QoL over a two-year period; however, the depressive symptoms in this limited sample of men with prostate cancer was higher than expected and monitoring for these may be advisable for those who care for such patients.

  2. Synergistic killing effect of chloroquine and androgen deprivation in LNCaP cells

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    Kaini, Ramesh R. [Department of Biochemistry and Molecular Biology and UNM Cancer and Treatment Center, University of New Mexico Health Sciences Center, Albuquerque, NM (United States); Hu, Chien-An A., E-mail: AHu@salud.unm.edu [Department of Biochemistry and Molecular Biology and UNM Cancer and Treatment Center, University of New Mexico Health Sciences Center, Albuquerque, NM (United States)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Chloroquine synergistically killed LNCaP cells during androgen deprivation treatment. Black-Right-Pointing-Pointer Chloroquine inhibited the function of autolysosomes and decreases the cytosolic ATP. Black-Right-Pointing-Pointer Chloroquine induced nuclear and DNA fragmentation in androgen deprived LNCaP. Black-Right-Pointing-Pointer Chloroquine may be an useful adjuvant in hormone ablation therapy in PCa patients. -- Abstract: Modulation of autophagy is a new paradigm in cancer therapeutics. Recently a novel function of chloroquine (CLQ) in inhibiting degradation of autophagic vesicles has been revealed, which raises the question whether CLQ can be used as an adjuvant in targeting autophagic pro-survival mechanism in prostate cancer (PCa). We previously showed that autophagy played a protective role during hormone ablation therapy, in part, by consuming lipid droplets in PCa cells. In addition, blocking autophagy by genetic and pharmacological means in the presence of androgen deprivation caused cell death in PCa cells. To further investigate the importance of autophagy in PCa survival and dissect the role of CLQ in PCa death, we treated hormone responsive LNCaP cells with CLQ in combination with androgen deprivation. We observed that CLQ synergistically killed LNCaP cells during androgen deprivation in a dose- and time-dependent manner. We further confirmed that CLQ inhibited the maturation of autophagic vesicles and decreased the cytosolic ATP. Moreover, CLQ induced nuclear condensation and DNA fragmentation, a hallmark of apoptosis, in androgen deprived LNCaP cells. Taken together, our finding suggests that CLQ may be an useful adjuvant in hormone ablation therapy to improve the therapeutic efficacy.

  3. Effects of recreational soccer in men with prostate cancer undergoing androgen deprivation therapy

    DEFF Research Database (Denmark)

    Uth, Jacob; Schmidt, Jakob Friis; Christensen, Jesper Frank

    2013-01-01

    Androgen deprivation therapy (ADT) is a cornerstone in the treatment of advanced prostate cancer. Adverse musculoskeletal and cardiovascular effects of ADT are widely reported and investigations into the potential of exercise to ameliorate the effects of treatment are warranted. The 'Football Club...

  4. Steroidogenic enzymes and stem cell markers are upregulated during androgen deprivation in prostate cancer

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    Pfeiffer, M.J.; Smit, F.P.; Sedelaar, J.P.M.; Schalken, J.A.

    2011-01-01

    Considerable levels of testosterone and dihydrotestosterone (DHT) are found in prostate cancer (PCa) tissue after androgen deprivation therapy. Treatment of surviving cancer-initiating cells and the ability to metabolize steroids from precursors may be the keystones for the appearance of recurrent

  5. An Update on the Changing Indications for Androgen Deprivation Therapy for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Kristene Myklak

    2011-01-01

    Full Text Available Quality of life has become increasingly more important for men diagnosed with prostate cancer. In light of this and the recognized risks of androgen deprivation therapy (ADT, the guidelines and use of ADT have changed significantly over the last few years. This paper reviews the current recommendations and the future perspectives regarding ADT. The benefits of ADT are evident neoadjuvantly and adjuvantly in patients treated with external beam radiation therapy for intermediate- and high-risk disease, in patients who have undergone prostatectomy with lymph node involvement, in high-risk patients after definitive therapy, and in patients who have developed progression or metastasis. Finally, this paper reviews the risks and benefits of each of these scenarios and the risks of androgen deprivation in general, and it delineates the areas where ADT was previously recommended, but where evidence is lacking for its additional benefit.

  6. The metabolic syndrome and its components in patients with prostate cancer on androgen deprivation therapy.

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    Morote, Juan; Gómez-Caamaño, Antonio; Alvarez-Ossorio, José L; Pesqueira, Daniel; Tabernero, Angel; Gómez Veiga, Francisco; Lorente, José A; Porras, Mariano; Lobato, Juan J; Ribal, María J; Planas, Jacques

    2015-06-01

    Androgen deprivation therapy may promote the development of the metabolic syndrome in patients with prostate cancer. We assessed the prevalence of the full metabolic syndrome and its components during the first year of androgen deprivation therapy. This observational, multicenter, prospective study included 539 patients with prostate cancer scheduled to receive 3-month depot luteinizing hormone-releasing hormone analogs for more than 12 months. Waist circumference, body mass index, lipid profile, blood pressure and fasting glucose were evaluated at baseline and after 6 and 12 months. The metabolic syndrome was assessed according to NCEP ATP III criteria (2001) and 4 other definitions (WHO 1998, AACE 2003, AHA/NHLBI 2005 and IDF 2005). At 6 and 12 months after the initiation of androgen deprivation therapy, significant increases were observed in waist circumference, body mass index, fasting glucose, triglycerides, total cholesterol, and high-density and low-density lipoprotein cholesterol. No significant changes in blood pressure 130/85 or greater were detected. A nonsignificant increase of 3.9% in the prevalence of the full metabolic syndrome (ATP III) was observed (22.9% at baseline vs 25.5% and 26.8% at 6 and 12 months, respectively). The prevalence of the metabolic syndrome at baseline varied according to the definition used, ranging from 9.4% (WHO) to 50% (IDF). At 12 months significant increases in prevalence were observed with the WHO (4.1%) and AHA/NHLBI (8.1%) definitions. Androgen deprivation therapy produces significant early effects on waist circumference, body mass index, fasting glucose, triglycerides and cholesterol. The prevalence of and increase in the metabolic syndrome depend on the defining criteria. Counseling patients on the prevention, early detection and treatment of specific metabolic alterations is recommended. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  7. PSA bounces after neoadjuvant androgen deprivation and external beam radiation: Impact on definitions of failure

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    Zietman, Anthony L.; Christodouleas, John P.; Shipley, William U.

    2005-01-01

    Purpose: To determine the characteristics of prostate specific antigen (PSA) bounces after external beam radiation therapy (EBRT) with neoadjuvant androgen deprivation and their impact on definitions of biochemical failure. Methods and Materials: Characteristics of bounce were calculated for all patients treated by EBRT with neoadjuvant androgen deprivation at our institution between 1992 and 1998 (preexclusion analysis). Calculations were repeated for the subgroup that satisfied additional inclusion/exclusion criteria (postexclusion analysis). The percentage of bounces scoring as false positives according to the ASTRO definition of biochemical failure was compared with those for three alternative definitions (Vancouver, Nadir-plus-two, and Nadir-plus-three) using McNemar's tests. Results: Thirty-nine percent (preexclusion cohort) and 56% (postexclusion cohort) of patients demonstrated a PSA bounce. Twenty percent (preexclusion analysis) and 25% (postexclusion analysis) of these bounces scored as biochemical failure according to the ASTRO definition. The Nadir-plus-three definition scored the smallest percentage of bounces as failure, but the difference between this definition and the ASTRO definition reached statistical significance in neither preexclusion nor postexclusion analyses (p ≥ 0.070). Conclusions: A substantial proportion of patients treated by EBRT with neoadjuvant deprivation experienced a PSA bounce. A large percentage of these bounces scored as biochemical failure according to the ASTRO definition. The Nadir-plus-three definition is less vulnerable to this bias

  8. Functional and structural changes in internal pudendal arteries underlie erectile dysfunction induced by androgen deprivation

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    Rhéure Alves-Lopes

    2017-01-01

    Full Text Available Androgen deficiency is strongly associated with erectile dysfunction (ED. Inadequate penile arterial blood flow is one of the major causes of ED. The blood flow to the corpus cavernosum is mainly derived from the internal pudendal arteries (IPAs; however, no study has evaluated the effects of androgen deprivation on IPA′s function. We hypothesized that castration impairs IPAs reactivity and structure, contributing to ED. In our study, Wistar male rats, 8-week-old, were castrated and studied 30 days after orchiectomy. Functional and structural properties of rat IPAs were determined using wire and pressure myograph systems, respectively. Protein expression was determined by Western blot and immunohistochemistry. Plasma testosterone levels were determined using the IMMULITE 1000 Immunoassay System. Castrated rats exhibited impaired erectile function, represented by decreased intracavernosal pressure/mean arterial pressure ratio. IPAs from castrated rats exhibited decreased phenylephrine- and electrical field stimulation (EFS-induced contraction and decreased acetylcholine- and EFS-induced vasodilatation. IPAs from castrated rats exhibited decreased internal diameter, external diameter, thickness of the arterial wall, and cross-sectional area. Castration decreased nNOS and α-actin expression and increased collagen expression, p38 (Thr180/Tyr182 phosphorylation, as well as caspase 3 cleavage. In conclusion, androgen deficiency is associated with impairment of IPA reactivity and structure and increased apoptosis signaling markers. Our findings suggest that androgen deficiency-induced vascular dysfunction is an event involving hypotrophic vascular remodeling of IPAs.

  9. Androgen deprivation therapy for prostate cancer: recommendations to improve patient and partner quality of life.

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    Elliott, Stacy; Latini, David M; Walker, Lauren M; Wassersug, Richard; Robinson, John W

    2010-09-01

    Because of improved prostate cancer detection, more patients begin androgen deprivation therapy (ADT) earlier and remain on it longer than before. Patients now may be androgen deprived for over a decade, even when they are otherwise free of cancer symptoms. An ADT Survivorship Working Group was formed to develop and evaluate interventions to limit the physiological and emotional trauma patients and their partners experience from this treatment. The multidisciplinary Working Group met for 2 days to define the challenges couples face when patients commence ADT. A writing sub-group was formed. It compiled the meeting's proceedings, reviewed the literature and, in consultation with the other members of the working group, wrote the manuscript. Expert opinion of the side effects of ADT that affect the quality of life (QOL) of patients and their partners and the recommendations for managing ADT to optimize QOL were based on the best available literature, clinical experience, and widespread internal discussions among Working Group members. Side effects identified as particularly challenging include: (i) body feminization; (ii) changes in sexual performance; (iii) relationship changes; (iv) cognitive and affective symptoms; and (v) fatigue, sleep disturbance, and depression. Recommendations for managing ADT include providing information about ADT side effects before administration of ADT, and, where appropriate, providing referrals for psychosocial support. Sexual rehabilitation principles for persons with chronic illness may prove useful. Psychological interventions for sexual sequelae need to be offered and individualized to patients, regardless of their age or partnership. Support should also be offered to partners. Our hope is that this plan will serve as a guide for optimizing how ADT is carried out and improve the lives of androgen-deprived men and their intimate partners. © 2010 International Society for Sexual Medicine.

  10. Preferred treatment frequency in patients receiving androgen deprivation therapy for advanced prostate cancer

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    Fode, Mikkel; Nielsen, Torben K; Al-Hamadani, Muhammad

    2014-01-01

    OBJECTIVE: The aim of this study was to assess patient preference regarding the length of treatment intervals of androgen deprivation therapy (ADT) with gonadotropin-releasing hormone agonists for prostate cancer. MATERIAL AND METHODS: The study was conducted as a questionnaire-based, cross...... the pressure on healthcare systems and may be of benefit for a large group of patients. However, it cannot be prescribed blindly without possibly affecting patient satisfaction. The choice of treatment intervals should be made in collaboration between the physician and the patient....

  11. Preferred treatment frequency in patients receiving androgen deprivation therapy for advanced prostate cancer

    DEFF Research Database (Denmark)

    Fode, Mikkel; Nielsen, Torben K; Al-Hamadani, Muhammad

    2014-01-01

    OBJECTIVE: The aim of this study was to assess patient preference regarding the length of treatment intervals of androgen deprivation therapy (ADT) with gonadotropin-releasing hormone agonists for prostate cancer. MATERIAL AND METHODS: The study was conducted as a questionnaire-based, cross...... satisfaction and side-effects. Overall, 238 men receiving ADT for prostate cancer were presented with the questionnaire between September 2011 and May 2012. Descriptive statistics, the chi-squared test and multiple regression were used for analyses. RESULTS: In total, 176 questionnaires (74%) were available...

  12. Cognitive Impairment in Men with Prostate Cancer Treated with Androgen Deprivation Therapy: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Sun, Maxine; Cole, Alexander P; Hanna, Nawar; Mucci, Lorelei A; Berry, Donna L; Basaria, Shehzad; Ahern, David K; Kibel, Adam S; Choueiri, Toni K; Trinh, Quoc-Dien

    2018-02-02

    Use of androgen deprivation therapy may increase the risk of cognitive impairment in men with prostate cancer. We performed a systematic review of the risk of overall cognitive impairment as an outcome in men receiving androgen deprivation therapy for prostate cancer. Studies were identified through PubMed®, MEDLINE®, PsycINFO®, Cochrane Library and Web of Knowledge/Science™. Articles were included if they 1) were published in English, 2) had subjects treated for prostate cancer with androgen deprivation therapy, 3) incorporated longitudinal comparisons and 4) used control groups. In addition, prospective studies were required to assess an established cognitive related end point using International Cognition and Cancer Task Force criteria defining impaired cognitive performance as scoring 1.5 or more standard deviations below published norms on 2 or more tests, or scoring 2.0 or more standard deviations below published norms on at least 1 test. The effect of androgen deprivation therapy on cognitive impairment was pooled using a random effects model. Of 221 abstracts 26 were selected for full text review, and 2 prospective and 4 retrospective studies were analyzed. Androgen deprivation therapy was not associated with overall cognitive impairment when the prospective cohort studies were pooled (OR 1.57, 95% CI 0.50 to 4.92, p = 0.44) with significant heterogeneity between estimates (I 2 = 83%). In retrospective data the relative risk of any cognitive impairment, including senile dementia and Alzheimer disease, was increased in men receiving androgen deprivation therapy, although the difference was not statistically significant (HR 1.28, 95% CI 0.93 to 1.76, p = 0.13) with moderate heterogeneity between estimates (I 2 = 67%). Analyses between overall cognitive impairment and use of androgen deprivation therapy defined according to International Cognition and Cancer Task Force criteria in a pooled analysis were inconclusive. In retrospective cohort studies the

  13. Androgen deprivation in prostate cancer and the long-term risk of fracture.

    Science.gov (United States)

    Ojeda, S; Lloret, M; Naranjo, A; Déniz, F; Chesa, N; Domínguez, C; Lara, P C

    2017-10-01

    To determine the rate of bone mass loss and the risk of fracture induced by androgen deprivation therapy in patients with prostate cancer. Prospective study in 2 phases. In the first phase, demographic variables, FRAX ® , bone mineral density and clinical fractures were collected, before starting the therapy and up to 1 year after ending the therapy. In the second phase, we conducted a telephone interview a mean of 8.5 years after the start of the study to assess new fractures. We included 150 patients with a mean age of 67 years and a mean therapy duration of 24 months. Before starting the treatment, 62 patients (41%) showed osteoporosis or low bone mass in the densitometry. After the first year of treatment, the bone mineral density decreased a mean of 3.7% and 2.1% in the lumbar spine and femoral neck, respectively. At the end of the second and third year, the loss rate was lower. During the first phase of the study, 4 patients (2.7%) experienced a fracture. In the telephone interviews with 80 patients (53%), only 1 had experienced a fracture. In the patients with prostate cancer and androgen deprivation therapy, greater bone loss occurred during the first year. When the treatment did not exceed 2 years, the absolute risk of fracture was low, and clinical fractures were uncommon in the short and long term. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Androgen deprivation therapy (castration therapy and pedophilia: What’s new

    Directory of Open Access Journals (Sweden)

    Mauro Silvani

    2015-09-01

    Full Text Available Andrology is a constantly evolving discipline, embracing social problems like pedophilia and its pharmacological treatment. With regard to chemical castration, the andrologist may perform an important role as part of a team of specialists. At present, no knowledge is available regarding hormonal, chromosomal or genetic alterations involved in pedophilia. International legislation primarily aims to defend childhood, but does not provide for compulsory treatment. We reviewed international literature that, at present, only comprises a few reports on research concerning androgen deprivation. Most of these refer to the use of leuprolide acetate, rather than medroxyprogesterone and cyproterone acetate, which present a larger number of side effects. Current opinions on chemical castration for pedophilia are discordant. Some surveys confirm that therapy reduces sexual thoughts and fantasies, especially in recidivism. On the other hand, some authors report that chemical castration does not modify the pedophile’s personality. In our opinion, once existing legislation has changed, andrologists could play a significant role in the selection of patients to receive androgen deprivation therapy, due in part to their knowledge about its action and side effects.

  15. Tissue polypeptide-specific antigen (TPS) determinations before and during intermittent maximal androgen blockade in patients with metastatic prostatic carcinoma

    NARCIS (Netherlands)

    Kil, P. J. M.; Goldschmidt, H. M. J.; Wieggers, B. J. A.; Kariakine, O. B.; Studer, U. E.; Whelan, P.; Hetherington, J.; de Reijke, Th M.; Hoekstra, J. W.; Collette, L.

    2003-01-01

    To evaluate the prognostic significance of serially measured tissue polypeptide-specific antigen (TPS) levels in patients with metastatic prostatic carcinoma treated with intermittent maximal androgen blockade (MAB). To determine its value with respect to predicting response to treatment and time to

  16. Adjuvant androgen deprivation therapy augments cure and long-term cancer control in men with poor prognosis, nonmetastatic prostate cancer.

    NARCIS (Netherlands)

    Fleshner, N.; Keane, T.E.; Lawton, C.A.; Mulders, P.F.A.; Payne, H.; Taneja, S.S.; Morris, T.

    2008-01-01

    Historically, adjuvant androgen deprivation therapy has been viewed as a palliative treatment option for patients with poor-prognosis non-metastatic prostate cancer. In addition, guidelines from bodies such as the European Association of Urology and American Society for Clinical Oncology do not

  17. Hot flushes in prostatic cancer patients during androgen-deprivation therapy with monthly dose of degarelix or leuprolide

    DEFF Research Database (Denmark)

    Iversen, P; Karup, C; van der Meulen, E

    2011-01-01

    The aim of the study was to compare the onset, incidence and frequency/intensity of hot flushes during androgen-deprivation therapy with a gonadotropin-releasing hormone antagonist (GnRH) blocker versus an agonist using data from a randomized Phase 3 clinical trial. In total, 610 prostate cancer...

  18. Integrating diet and exercise into care of prostate cancer patients on androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Moyad MA

    2016-08-01

    Full Text Available Mark A Moyad,1 Robert U Newton,2 Ulf W Tunn,3 Damian Gruca4 1Department of Urology, University of Michigan Medical Center, Ann Arbor, MI, USA; 2Exercise Medicine Research Institute, Edith Cowan University, Joondalup, WA, Australia; 3Urological Clinic, Facharztzentrum Academic Hospital Sana Klinikum Offenbach, Offenbach/Main, 4Global Medical Affairs, AbbVie Deutschland, Ludwigshafen, Germany Abstract: Improved diagnosis and treatment regimens have resulted in greater longevity for men with prostate cancer. This has led to an increase in both androgen deprivation therapy (ADT use and duration of exposure, and therefore to its associated adverse effects, such as sexual dysfunction, osteoporosis, reduced muscle mass, increased fat mass, and increased incidence of cardiovascular disease and type 2 diabetes. Given that the adverse effects of ADT are systemic, often debilitating, and difficult to treat, efforts continue in the development of new strategies for long-term management of prostate cancer. The PubMed database was searched to select trials, reviews, and meta-analyses in English using such search terms as “prostate cancer” and “androgen deprivation therapy”, “cardiovascular risk”, “lean body mass”, “exercise”, and “diet”. The initial searches produced 379 articles with dates 2005 or more recent. Articles published after 2004 were favored. This review utilizes the latest data to provide a status update on the effects of exercise and diet on patients with prostate cancer, focusing on ADT-associated side effects, and it discusses the evidence for such interventions. Since the evidence of large-scale trials in patients with prostate cancer is missing, and an extrapolation of supporting data to all patient subgroups cannot be provided, individualized risk assessments remain necessary before the initiation of exercise and diet programs. Exercise, diet, and nutritional supplementation interventions have the potential to

  19. Hypoxia-Independent Downregulation of Hypoxia-Inducible Factor 1 Targets by Androgen Deprivation Therapy in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ragnum, Harald Bull [Department of Radiation Biology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Røe, Kathrine [Department of Radiation Biology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Division of Medicine, Department of Oncology, Akershus University Hospital, Lørenskog (Norway); Holm, Ruth; Vlatkovic, Ljiljana [Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Nesland, Jahn Marthin [Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Medical Faculty, University of Oslo, Oslo (Norway); Aarnes, Eva-Katrine [Department of Radiation Biology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Ree, Anne Hansen [Division of Medicine, Department of Oncology, Akershus University Hospital, Lørenskog (Norway); Medical Faculty, University of Oslo, Oslo (Norway); Flatmark, Kjersti [Department of Tumor Biology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Department of Gastrointestinal Surgery, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Seierstad, Therese [Department of Radiology and Nuclear Medicine, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Faculty of Health Sciences, Buskerud University College, Drammen (Norway); Lilleby, Wolfgang [Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Lyng, Heidi, E-mail: heidi.lyng@rr-research.no [Department of Radiation Biology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway)

    2013-11-15

    Purpose: We explored changes in hypoxia-inducible factor 1 (HIF1) signaling during androgen deprivation therapy (ADT) of androgen-sensitive prostate cancer xenografts under conditions in which no significant change in immunostaining of the hypoxia marker pimonidazole had occurred. Methods and Materials: Gene expression profiles of volume-matched androgen-exposed and androgen-deprived CWR22 xenografts, with similar pimonidazole-positive fractions, were compared. Direct targets of androgen receptor (AR) and HIF1 transcription factors were identified among the differentially expressed genes by using published lists. Biological processes affected by ADT were determined by gene ontology analysis. HIF1α protein expression in xenografts and biopsy samples from 35 patients receiving neoadjuvant ADT was assessed by immunohistochemistry. Results: A total of 1344 genes showed more than 2-fold change in expression by ADT, including 35 downregulated and 5 upregulated HIF1 targets. Six genes were shared HIF1 and AR targets, and their downregulation was confirmed with quantitative RT-PCR. Significant suppression of the biological processes proliferation, metabolism, and stress response in androgen-deprived xenografts was found, consistent with tumor regression. Nineteen downregulated HIF1 targets were involved in those significant biological processes, most of them in metabolism. Four of these were shared AR and HIF1 targets, including genes encoding the regulatory glycolytic proteins HK2, PFKFB3, and SLC2A1. Most of the downregulated HIF1 targets were induced by hypoxia in androgen-responsive prostate cancer cell lines, confirming their role as hypoxia-responsive HIF1 targets in prostate cancer. Downregulation of HIF1 targets was consistent with the absence of HIF1α protein in xenografts and downregulation in patients by ADT (P<.001). Conclusions: AR repression by ADT may lead to downregulation of HIF1 signaling independently of hypoxic fraction, and this may contribute to

  20. Hypoxia-Independent Downregulation of Hypoxia-Inducible Factor 1 Targets by Androgen Deprivation Therapy in Prostate Cancer

    International Nuclear Information System (INIS)

    Ragnum, Harald Bull; Røe, Kathrine; Holm, Ruth; Vlatkovic, Ljiljana; Nesland, Jahn Marthin; Aarnes, Eva-Katrine; Ree, Anne Hansen; Flatmark, Kjersti; Seierstad, Therese; Lilleby, Wolfgang; Lyng, Heidi

    2013-01-01

    Purpose: We explored changes in hypoxia-inducible factor 1 (HIF1) signaling during androgen deprivation therapy (ADT) of androgen-sensitive prostate cancer xenografts under conditions in which no significant change in immunostaining of the hypoxia marker pimonidazole had occurred. Methods and Materials: Gene expression profiles of volume-matched androgen-exposed and androgen-deprived CWR22 xenografts, with similar pimonidazole-positive fractions, were compared. Direct targets of androgen receptor (AR) and HIF1 transcription factors were identified among the differentially expressed genes by using published lists. Biological processes affected by ADT were determined by gene ontology analysis. HIF1α protein expression in xenografts and biopsy samples from 35 patients receiving neoadjuvant ADT was assessed by immunohistochemistry. Results: A total of 1344 genes showed more than 2-fold change in expression by ADT, including 35 downregulated and 5 upregulated HIF1 targets. Six genes were shared HIF1 and AR targets, and their downregulation was confirmed with quantitative RT-PCR. Significant suppression of the biological processes proliferation, metabolism, and stress response in androgen-deprived xenografts was found, consistent with tumor regression. Nineteen downregulated HIF1 targets were involved in those significant biological processes, most of them in metabolism. Four of these were shared AR and HIF1 targets, including genes encoding the regulatory glycolytic proteins HK2, PFKFB3, and SLC2A1. Most of the downregulated HIF1 targets were induced by hypoxia in androgen-responsive prostate cancer cell lines, confirming their role as hypoxia-responsive HIF1 targets in prostate cancer. Downregulation of HIF1 targets was consistent with the absence of HIF1α protein in xenografts and downregulation in patients by ADT (P<.001). Conclusions: AR repression by ADT may lead to downregulation of HIF1 signaling independently of hypoxic fraction, and this may contribute to

  1. The use of exercise interventions to overcome adverse effects of androgen deprivation therapy

    DEFF Research Database (Denmark)

    Østergren, Peter Busch; Kistorp, Caroline; Bennedbæk, Finn Noe

    2016-01-01

    existing cardiovascular disease. In this initial phase of ADT, metabolic changes are also most prominent. In addition, ADT increases the rate of bone loss and fracture risk. Currently available evidence supports the use of exercise interventions to improve physical function and mitigate ADT-induced fatigue......Androgen deprivation therapy (ADT) induces severe hypogonadism and is associated with several adverse effects that negatively affect health and quality of life in patients with prostate cancer. ADT changes body composition characterized by an increase in fat mass and a reduction in muscle mass....... Some studies also indicate that exercise might moderate ADT-related changes in body composition. However, beneficial effects of exercise interventions on other ADT-related conditions have not been conclusively proven. Trials investigating the effects of ADT on fracture risk and development of diabetes...

  2. Football training in men with prostate cancer undergoing androgen deprivation therapy

    DEFF Research Database (Denmark)

    Uth, Jacob; Hornstrup, Therese; Christensen, Jesper F

    2016-01-01

    ) and density, BTMs and postural balance. RESULTS: In the last part of the 12 weeks, FTG performed 194 ± 41 accelerations and 296 ± 65 decelerations at >0.6 m/s/s and covered a distance of 905 ± 297 m at speeds >6 km/h and 2646 ± 705 m per training session. Analysis of baseline-to-12-week change scores showed......PURPOSE: To investigate the activity profile of football training and its short-term effects on bone mass, bone turnover markers (BTMs) and postural balance in men with prostate cancer (PCa) undergoing androgen deprivation therapy (ADT). METHODS: This was a randomised 12-week study in which men...

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

    Science.gov (United States)

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

    2014-01-01

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

  4. Rising prostate-specific antigen values during neoadjuvant androgen deprivation therapy: The importance of monitoring

    International Nuclear Information System (INIS)

    Niblock, Paddy; Pickles, Tom

    2006-01-01

    Purpose: To assess the impact of a rising prostate-specific antigen (PSA) level in patients receiving neoadjuvant androgen deprivation therapy (N-ADT) before external beam radiotherapy for prostate cancer. Methods and Materials: From prospectively collected data, we identified 182 patients who received between 3 and 12 months of N-ADT before definitive external beam radiotherapy and who had at least three PSA readings during the neoadjuvant period. One hundred fifty patients had PSA values that continued to fall (Non-Rise group), but 32 had a PSA value that started to rise (Rise group). The two groups were compared by Mann-Whitney U and Pearson chi-square tests. Kaplan-Meier and log-rank analyses were performed for time to treatment failure, cause-specific survival (CSS), and overall survival (OS). Results: The median follow-up was 62.5 months for the Non-Rise group and 53 months for the Rise group. Patients who sustained a PSA rise during the N-ADT period had a shorter time to PSA relapse (p = 0.013), poorer CSS (p = 0.027), and poorer OS (p = 0.03). Multivariate analysis confirms the significance of a PSA rise during the N-ADT period for CSS (p = 0.035) and OS (p = 0.038). Conclusions:: A subset of patients treated with N-ADT develop a rising PSA profile that likely represents early androgen resistance. They have significantly worse outcome

  5. Phase II study of neoadjuvant androgen deprivation followed by external-beam radiotherapy with 9 months of androgen deprivation for intermediate- to high-risk localized prostate cancer.

    Science.gov (United States)

    Heymann, Jonas J; Benson, Mitchell C; O'Toole, Kathleen M; Malyszko, Bozena; Brody, Rachel; Vecchio, Darleen; Schiff, Peter B; Mansukhani, Mahesh M; Ennis, Ronald D

    2007-01-01

    To evaluate the toxicity and efficacy of individualized neoadjuvant androgen deprivation (AD) to maximal response followed by external beam radiotherapy (RT) with continued AD for a total of 9 months in a prospective phase II trial. One hundred twenty-three patients received a total of 9 months of flutamide and luprolide combined with RT. RT initiation was individualized to begin after maximum response to AD as assessed by monthly digital rectal examination and prostate-specific antigen (PSA). The neoadjuvant phase was restricted to no more than 6 months. Median time to initiation of RT was 4.7 months. Indications to begin RT (and their rates) were undetectable PSA (28%), PSA unchanged from one month to the next (46%), PSA rising from one month to the next (10%), 6 months of AD (14%), and other (2%). Five-year outcomes were biochemical disease-free survival, (DFS) 63% +/- 7%; clinical DFS, 75% +/- 5%; cancer-specific survival, 99% +/- 1%; and overall survival, 89% +/- 3%. Patients initiating RT after 6 months of AD had significantly lower biochemical and clinical DFS. Those patients whose testosterone recovered to normal after completion of AD had a significantly superior survival rate. Of those patients potent before treatment, 65% remained so at last follow-up. The combination of 9 months of AD and RT, with initiation of RT individualized on the basis of maximum response to AD, achieves disease control rates comparable with past studies, while preserving potency in many patients. Further studies are warranted to determine the optimal combination of AD and RT in this patient population.

  6. To Die or to Survive, a Fatal Question for the Destiny of Prostate Cancer Cells after Androgen Deprivation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Kai-Xin; Firus, Jessica; Prieur, Brenda [The Vancouver Prostate Centre, 2660 Oak St., Vancouver, BC V6H 3Z6 (Canada); Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6 (Canada); Jia, William [Department of Surgery and Brain Research Centre, University of British Columbia, Vancouver, BC V6H 3Z6 (Canada); Rennie, Paul S., E-mail: prennie@interchange.ubc.ca [The Vancouver Prostate Centre, 2660 Oak St., Vancouver, BC V6H 3Z6 (Canada); Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6 (Canada)

    2011-03-24

    Prostate cancer is the most frequently diagnosed non-skin cancer in adult males in North America and is the second leading cause of cancer-related mortality. For locally advanced or metastatic disease, androgen deprivation, through medical or surgical castration, is the primary treatment to induce prostate cancer cell death and extend patient survival. However, the vast majority of cancers progress to a castration-resistant/androgen-independent state where the cell death processes are no longer active. This review describes the main cell death processes, apoptosis, autophagy, necrosis and necroptosis, which may be activated in prostate cancers after androgen deprivation therapy as well as the molecular mechanisms through which the cancers progress to become castration resistant. In particular, the central role of persistent androgen receptor (AR)-mediated signaling and AR crosstalk with other critical cell signaling pathways, including (i) the PI3K/Akt pathway, (ii) receptor tyrosine kinases, (iii) the p38 MAPK pathway, and (iv) the Wnt/β-catenin pathway, as well as reactivation of AR by de novo synthesized androgen are discussed in this context. Understanding the molecular changes that subvert normal cell death mechanisms and thereby compromise the survival of prostate cancer patients continues to be a major challenge.

  7. Significance of pretreatment cardiovascular morbidity as a risk factor during treatment with parenteral oestrogen or combined androgen deprivation of 915 patients with metastasized prostate cancer

    DEFF Research Database (Denmark)

    Hedlund, Per Olov; Johansson, Robert; Damber, Jan Erik

    2011-01-01

    This study aimed to evaluate prognostic risk factors for cardiovascular events during treatment of metastatic prostate cancer patients with high-dose parenteral polyoestradiol phosphate (PEP, Estradurin®) or combined androgen deprivation (CAD) with special emphasis on pretreatment cardiovascular...

  8. A Prospective Audit of Intermittent Anti-Androgen verses Pituitary Blockade Suggests a Bipolar Androgen Type Strategy May Be Safe in Untreated Prostate Cancer.

    Science.gov (United States)

    Oliver, Timothy; Wilson, Peter; Ansell, Wendy; Philp, Tim; Chinegwundoh, Frank; Shamash, Jonathan; Shaw, Greg; Ahmad, Amar

    2018-01-01

    A locally advanced Gleason 4 + 4 prostate cancer patient who was on self-medication with intermittent anti-androgen monotherapy (iAAm) over 14 years suggested that raised testosterone was not dangerous and this suggestion needed investigating. Others who were on AA continuously were recruited to ongoing audit of intermittent hormone therapy (IHT) and iAAm outcomes were compared with intermittent LHRH therapy (iLHRH or iMAB). Between 1994 and 2007, 111 patients sought IHT because of side effects of treatment. Forty-two M0 patients received IHT with iLHRHm or iMAB and 33 received iAAm (31 of these were M0). PSA nadir below 4 was necessary for entry. Overall survival was 87, 72 and 67% with iAAm and 73, 56 and 43% with iLHRH/MAB at 5, 8 and 10 years respectively. Overall survival was 61, 55 and 33% continued on iAAm and 56, 41, and 32% on iLHRH/MAB at 5, 8, and 10 years respectively. Multivariable analysis and matched case control analysis confirm that the maintenance of advantage for iAAm Testosterone levels in patients on iAAm compared to iLHRH therapy was more intense throughout treatment. These results complement recent progress in using bipolar androgen therapy to reverse castration resistance and add to the increasing acceptance that controlled testosterone exposure might be relevant in hormone-naïve patients. © 2017 S. Karger AG, Basel.

  9. [Clinical Study of 2014 ISUP New Grade Group Classification for Prostate Cancer Patients Treated by Androgen Deprivation Therapy].

    Science.gov (United States)

    Uno, Masahiro; Kawase, Makoto; Kato, Daiki; Ishida, Takashi; Kato, Seiichi; Fujimoto, Yoshinori

    2018-01-01

    The 2014 International Society of Urological Pathology (ISUP) has proposed a new grade group (GG) classification for Gleason scores (GS). The usefulness of the new GG classification was investigated with 518 prostate cancer patients who underwent androgen deprivation therapy. According to the new GG classification, Stages B‒D and the new GG classification relapse-free rate for each stage were calculated using the Kaplan‒Meier method. The new GG classification revealed a significant difference for the relapse-free rate only between some groups. Analysis using the Cox proportional hazards model indicated that the risk of relapse was higher in GGs 4 and 5 than in GG 1. The usefulness about the relapse-free rate in androgen deprivation therapy of the 2014 ISUP new grade group classification a waits future examination.

  10. [Osteoporosis fracture in a male patient secondary to hypogonadism due to androgen deprivation treatment for prostate cancer].

    Science.gov (United States)

    Verdú Solans, J; Roig Grau, I; Almirall Banqué, C

    2014-01-01

    A 84 year-old patient, in therapy with androgen deprivation during the last 5 years due a prostate cancer, is presented with a osteoporotic fracture of the first lumbar vertebra. The pivotal role of the primary care physician, in the prevention of the osteoporosis secondary to the hypogonadism in these patients, is highlighted. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  11. The sexuality and social performance of androgen-deprived (castrated) men throughout history: implications for modern day cancer patients.

    Science.gov (United States)

    Aucoin, Michael William; Wassersug, Richard Joel

    2006-12-01

    Androgen-deprivation therapy (ADT) via either surgical or chemical castration is the standard treatment for advanced prostate cancer (PCa). In North America, it is estimated that more than 40,000 men start ADT each year. The side effects of this treatment are extensive and include gynecomastia, erectile dysfunction, and reduced libido. These changes strongly challenge patients' self-identity and sexuality. The historical term for a man who has been castrated is 'eunuch', now a pejorative term implying overall social and sexual impotence. In this paper, we review key historical features of eunuch social performance and sexuality from a variety of cultures in order to assess the validity of contemporary stereotypes of the androgen-deprived male. Data were taken from secondary sources on the history of Byzantium, Roman Antiquity, Early Islamic societies, the Ottoman Empire, Chinese Dynasties, and the Italian Castrati period. This cross-cultural survey shows that castrated men consistently held powerful social positions that yielded great political influence. Many eunuchs were recognized for their loyalty, managerial style, wisdom, and pedagogical skills. Furthermore, rather than being consistently asexual and celibate, they were often sexually active. In certain cultures, they were objects of sexual desire for males, or females, or both. Collectively, the historical accounts suggest that, given the right cultural setting and individual motivation, androgen deprivation may actually enhance rather than hinder both social and sexual performance. We conclude that eunuch history contradicts the presumption that androgen deprivation necessarily leads to social and sexual impotence. The capabilities and accomplishments of eunuchs in the past gives patients on ADT grounds for viewing themselves in a positive light, where they are neither socially impotent nor sexually chaste.

  12. Acceptability of short term neo-adjuvant androgen deprivation in patients with locally advanced prostate cancer

    International Nuclear Information System (INIS)

    Lamb, David S.; Denham, James W.; Mameghan, Hedy; Joseph, David; Turner, Sandra; Matthews, John; Franklin, Ian; Atkinson, Chris; North, John; Poulsen, Michael; Kovacev, Olga; Robertson, Randall; Francis, Lynne; Christie, David; Spry, Nigel A.; Tai, K.-H.; Wynne, Chris; Duchesne, Gillian

    2003-01-01

    Purpose: To determine the acceptability of short term neo-adjuvant maximal androgen deprivation (MAD) to patients treated with external beam radiation for locally advanced prostate cancer. Methods: Between 1996 and 2000, 818 patients with locally advanced, but non-metastatic, prostate cancer were entered into a randomised clinical trial (TROG 96.01), which compared radiation treatment alone with the same radiation treatment and 3 or 6 months neo-adjuvant MAD with goserelin and flutamide. Relevant symptoms, and how troublesome they were to the patient, were scored using a self-assessment questionnaire. This was completed by the patient at registration, and at specified times during and after treatment. Patients taking flutamide had liver function tests checked at regular intervals. Results: All patients have completed at least 12 months follow-up after treatment. Nearly all patients completed planned treatment with goserelin, but 27% of patients in the 6-month MAD treatment arm, and 20% in the 3-month arm, had to stop flutamide early. This was mainly due to altered liver function (up to 17% patients) and bowel side effects (up to 8% patients). However, although flutamide resulted in more bowel symptoms for patients on MAD, there was significant reduction in some urinary symptoms on this treatment. Acute bowel and urinary side effects at the end of radiation treatment were similar in all treatment arms. Side effect severity was unrelated to radiation target volume size, which was reduced by MAD, but symptomatology prior to any treatment was a powerful predictor. Of the 36% of patients who were sexually active before any treatment, the majority became inactive whilst on MAD. However, sexual activity at 12 months after radiation treatment was similar in all treatment arms, indicating that the effects of short term MAD on sexual function are reversible. Conclusion: Despite temporary effects on sexual activity, and compliance difficulties with flutamide, short-term neo

  13. Duration of Androgen Deprivation Therapy Influences Outcomes for Patients Receiving Radiation Therapy Following Radical Prostatectomy.

    Science.gov (United States)

    Jackson, William C; Schipper, Matthew J; Johnson, Skyler B; Foster, Corey; Li, Darren; Sandler, Howard M; Palapattu, Ganesh S; Hamstra, Daniel A; Feng, Felix Y

    2016-01-01

    Limited data exist to guide the use of androgen deprivation therapy (ADT) for men treated with radiation therapy (RT) after radical prostatectomy (RP). The optimal duration of ADT in this setting is unknown. To determine if the duration of ADT influences clinical outcomes for men receiving post-RP RT. A total of 680 men who received adjuvant radiation therapy (n=105) or salvage radiation therapy (n=575) between 1986 and 2010 at a single tertiary care institution were reviewed retrospectively. Median follow-up post-RT was 57.8 mo. RT was delivered using three-dimensional conformal or intensity-modulated RT in 1.8-Gy fractions. For patients treated with ADT, >80% were treated with a gonadotropin-releasing hormone agonist with or without a nonsteroidal antiandrogen. Biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall mortality were assessed using Kaplan-Meier analysis and propensity score analysis. Overall, 144 patients (21%) received ADT with post-RP RT, most of whom had high-risk disease features such as Gleason score 8-10, seminal vesicle invasion, or pre-RT prostate-specific antigen >1 ng/ml. Median ADT duration was 12 mo (interquartile range: 6.0-23.7). Patients who received HR]: 2.27; p=0.003) and DM (HR: 2.48; p=0.03) compared with patients receiving ≥12 mo of ADT. The 5-yr rates of DM were 6.0% and 23% for ≥12 and controlling for pretreatment and treatment-related factors, each month of ADT was associated with a decreased risk for BF (HR: 0.95; p=0.0004), DM (HR: 0.88; p=0.0004), and PCSM (HR: 0.90; p=0.037). These findings are limited by the retrospective nature of our analysis. For men with high-risk disease features receiving ADT with post-RP RT, the duration of ADT is associated with clinical outcomes. Our findings suggest that for these men an extended course of ADT ≥12 mo may be preferable. Validation of our findings is needed. We evaluated outcomes for men with high-risk disease features

  14. Impact of Concurrent Androgen Deprivation on Fiducial Marker Migration in External-beam Radiation Therapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tiberi, David A.; Carrier, Jean-Francois; Beauchemin, Marie-Claude; Nguyen, Thu Van; Beliveau-Nadeau, Dominic [Departement de Radio-Oncologie, Centre hospitalier de l' Universite de Montreal-Hopital Notre-Dame, Montreal, Quebec (Canada); Taussky, Daniel, E-mail: daniel.taussky.chum@ssss.gouv.qc.ca [Departement de Radio-Oncologie, Centre hospitalier de l' Universite de Montreal-Hopital Notre-Dame, Montreal, Quebec (Canada)

    2012-09-01

    Purpose: To determine the extent of gold fiducial marker (FM) migration in patients treated for prostate cancer with concurrent androgen deprivation and external-beam radiation therapy (EBRT). Methods and Materials: Three or 4 gold FMs were implanted in 37 patients with prostate adenocarcinoma receiving androgen deprivation therapy (ADT) in conjunction with 70-78 Gy. Androgen deprivation therapy was started a median of 3.9 months before EBRT (range, 0.3-12.5 months). To establish the extent of FM migration, the distance between each FM was calculated for 5-8 treatments once per week throughout the EBRT course. For each treatment, the distance between FMs was compared with the distance from the digitally reconstructed radiographs generated from the planning CT. A total of 281 treatments were analyzed. Results: The average daily migration was 0.8 {+-} 0.3 mm, with distances ranging from 0.2 mm-2.6 mm. Two of the 281 assessed treatments (0.7%) showed migrations >2 mm. No correlation between FM migration and patient weight or time delay between ADT and start of EBRT was found. There was no correlation between the extent of FM migration and prostate volume. Conclusion: This is the largest report of implanted FM migration in patients receiving concomitant ADT. Only 0.7% of the 281 treatments studied had significant marker migrations (>2 mm) throughout the course of EBRT. Consequently, the use of implanted FMs in these patients enables accurate monitoring of prostate gland position during treatment.

  15. Obesity and the Odds of Weight Gain following Androgen Deprivation Therapy for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Lior Z. Braunstein

    2014-01-01

    Full Text Available Background. Increasing body mass index (BMI is associated with increased risk of mortality; however, quantifying weight gain in men undergoing androgen deprivation therapy (ADT for prostate cancer (PC remains unexplored. Methods. Between 1995 and 2001, 206 men were enrolled in a randomized trial evaluating the survival difference of adding 6 months of ADT to radiation therapy (RT. BMI measurements were available in 171 men comprising the study cohort. The primary endpoint was weight gain of ≥10 lbs by 6-month followup. Logistic regression analysis was performed to assess whether baseline BMI or treatment received was associated with this endpoint adjusting for known prognostic factors. Results. By the 6-month followup, 12 men gained ≥10 lbs, of which 10 (83% received RT + ADT and, of these, 7 (70% were obese at randomization. Men treated with RT as compared to RT + ADT were less likely to gain ≥10 lbs (adjusted odds ratio (AOR: 0.18 [95% CI: 0.04–0.89]; P=0.04, whereas this risk increased with increasing BMI (AOR: 1.15 [95% CI: 1.01–1.31]; P=0.04. Conclusions. Consideration should be given to avoid ADT in obese men with low- or favorable-intermediate risk PC where improved cancer control has not been observed, but shortened life expectancy from weight gain is expected.

  16. Influence of androgen deprivation therapy on the uptake of PSMA-targeted agents: Emerging opportunities challenges

    Energy Technology Data Exchange (ETDEWEB)

    Bakht, Martin K.; Oh, So Won; Youn, Hye Won; Cheon, Gi Jeong; Kwak, Cheol; Kang, Keon Wook [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2017-09-15

    Prostate-specific membrane antigen (PSMA) is an attractive target for both diagnosis and therapy because of its high expression in the vast majority of prostate cancers. Development of small molecules for targeting PSMA is important for molecular imaging and radionuclide therapy of prostate cancer. Recent evidence implies that androgen-deprivation therapy increase PSMA-ligand uptake in some cases. The reported upregulations in PSMA-ligand uptake after exposure to second-generation antiandrogens such as enzalutamide and abiraterone might disturb PSMA-targeted imaging for staging and response monitoring of patients undergoing treatment with antiandrogen-based drugs. On the other hand, second-generation antiandrogens are emerging as potential endoradio-/chemosensitizers. Therefore, the enhancement of the therapeutic efficiency of PSMA-targeted theranostic methods can be listed as a new capability of antiandrogens. In this manuscript, we will present what is currently known about the mechanism of increasing PSMA uptake following exposure to antiandrogens. In addition, we will discuss whether these above-mentioned antiandrogens could play the role of endoradio-/chemosensitizers in combination with the well-established PSMA-targeted methods for pre-targeting of prostate cancer.

  17. Cardiometabolic and Skeletal Risk Factors in Black Men with Prostate Cancer Starting Androgen Deprivation Therapy

    International Nuclear Information System (INIS)

    Gunnarsson, Orvar; Basaria, Shehzad; Gignac, Gretchen A.

    2015-01-01

    Background: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with multiple metabolic complications, previously predominantly evaluated in the white population. Methods: A chart-based retrospective review was conducted on black patients with PCa, considered for ADT, from September 2007 to July 2010. Baseline data were collected on body mass index (BMI), vitamin-D status, bone mineral density (BMD), dyslipidemia and diabetes. Overweight and obesity were classified as BMI ≥ 25 and BMI ≥ 30, respectively. Vitamin-D sufficiency was defined as levels ≥30 ng/mL, insufficiency as <30 ng/mL and deficiency as ≤20 ng/mL. Osteopenia was defined as T scores between −1 to −2.5 and osteoporosis when T scores ≤−2.5. Results: Of the initial cohort of 130 black men, 111 (85.4%) patients underwent ADT. At baseline, average BMI was 28.1 ± 5.9 with 43.3% of men being overweight and 30.8% obese. More than one-third of the patients had pre-existing dyslipidemia while 28.8% were diabetics. 50% were vitamin-D deficient while 41% had low bone mass. Conclusions: Black men with PCa presenting for consideration of ADT have a high prevalence of existing metabolic risk factors. Close monitoring of this patient population is needed during ADT to prevent and treat metabolic complications

  18. Prostate Carcinogenesis with Diabetes and Androgen-Deprivation-Therapy-Related Diabetes: An Update

    Directory of Open Access Journals (Sweden)

    Noboru Hara

    2012-01-01

    Full Text Available Prostate cancer and the androgen deprivation therapy (ADT thereof are involved in diabetes in terms of diabetes-associated carcinogenesis and ADT-related metabolic disorder, respectively. The aim of this study is to systematically review relevant literature. About 218,000 men are estimated to be newly diagnosed with prostate cancer every year in the United States. Approximately 10% of them are still found with metastasis, and in addition to them, about 30% of patients with nonmetastatic prostate cancer recently experience ADT. Population-based studies have shown that dissimilar to other malignancies, type 2 diabetes is associated with a lower incidence of prostate cancer, whereas recent large cohort studies have reported the association of diabetes with advanced high-grade prostate cancer. Although the reason for the lower prevalence of prostate cancer among diabetic men remains unknown, the lower serum testosterone and PSA levels in them can account for the increased risk of advanced disease at diagnosis. Meanwhile, insulin resistance already appears in 25–60% of the patients 3 months after the introduction of ADT, and long-term ADT leads to a higher incidence of diabetes (reported hazard ratio of 1.28–1.44. Although the possible relevance of cytokines such as Il-6 and TNF-α to ADT-related diabetes has been suggested, its mechanism is poorly understood.

  19. Cardiometabolic and Skeletal Risk Factors in Black Men with Prostate Cancer Starting Androgen Deprivation Therapy

    Directory of Open Access Journals (Sweden)

    Orvar Gunnarsson

    2015-04-01

    Full Text Available Background: Androgen deprivation therapy (ADT for prostate cancer (PCa is associated with multiple metabolic complications, previously predominantly evaluated in the white population. Methods: A chart-based retrospective review was conducted on black patients with PCa, considered for ADT, from September 2007 to July 2010. Baseline data were collected on body mass index (BMI, vitamin-D status, bone mineral density (BMD, dyslipidemia and diabetes. Overweight and obesity were classified as BMI ≥ 25 and BMI ≥ 30, respectively. Vitamin-D sufficiency was defined as levels ≥30 ng/mL, insufficiency as <30 ng/mL and deficiency as ≤20 ng/mL. Osteopenia was defined as T scores between −1 to −2.5 and osteoporosis when T scores ≤−2.5. Results: Of the initial cohort of 130 black men, 111 (85.4% patients underwent ADT. At baseline, average BMI was 28.1 ± 5.9 with 43.3% of men being overweight and 30.8% obese. More than one-third of the patients had pre-existing dyslipidemia while 28.8% were diabetics. 50% were vitamin-D deficient while 41% had low bone mass. Conclusions: Black men with PCa presenting for consideration of ADT have a high prevalence of existing metabolic risk factors. Close monitoring of this patient population is needed during ADT to prevent and treat metabolic complications.

  20. Cardiometabolic and Skeletal Risk Factors in Black Men with Prostate Cancer Starting Androgen Deprivation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Gunnarsson, Orvar, E-mail: orvar.gunnarsson@uphs.upenn.edu [Department of Medicine, Division of Hematology and Oncology, Hospital of the University of Pennsylvania, 3400 Spruce Street, 16 Penn Tower, Philadelphia, PA 19104 (United States); Basaria, Shehzad [Department of Medicine, Section of Men’s Health, Aging and Metabolism, Brigham and Women’s Hospital, Boston, MA 02115 (United States); Gignac, Gretchen A. [Department of Medicine, Section of Hematology and Oncology, Boston University School of Medicine, Boston, MA 02118 (United States)

    2015-04-22

    Background: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with multiple metabolic complications, previously predominantly evaluated in the white population. Methods: A chart-based retrospective review was conducted on black patients with PCa, considered for ADT, from September 2007 to July 2010. Baseline data were collected on body mass index (BMI), vitamin-D status, bone mineral density (BMD), dyslipidemia and diabetes. Overweight and obesity were classified as BMI ≥ 25 and BMI ≥ 30, respectively. Vitamin-D sufficiency was defined as levels ≥30 ng/mL, insufficiency as <30 ng/mL and deficiency as ≤20 ng/mL. Osteopenia was defined as T scores between −1 to −2.5 and osteoporosis when T scores ≤−2.5. Results: Of the initial cohort of 130 black men, 111 (85.4%) patients underwent ADT. At baseline, average BMI was 28.1 ± 5.9 with 43.3% of men being overweight and 30.8% obese. More than one-third of the patients had pre-existing dyslipidemia while 28.8% were diabetics. 50% were vitamin-D deficient while 41% had low bone mass. Conclusions: Black men with PCa presenting for consideration of ADT have a high prevalence of existing metabolic risk factors. Close monitoring of this patient population is needed during ADT to prevent and treat metabolic complications.

  1. Prognostic significance of genetic polymorphisms in disease progression and survival in prostate cancer after androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Tsung-Yi Huang

    2015-06-01

    Full Text Available It is believed that androgens and their receptors regulate normal prostate growth and mediate prostate cancer development. Androgen deprivation therapy is the most commonly used treatment for advanced prostate cancer. Although the therapy is initially effective, progression of the disease to castration-resistant prostate cancer is almost inevitable, leading to treatment failure. Despite the existence of current clinical parameters, new biomarkers are urgently needed to improve the prognosis. Some molecules and DNA-based genetic biomarkers are under investigation as potential prognostic factors. The advancement in molecular cytogenetic research, such as genome-wide association for single-nucleotide polymorphisms, has made possible the detection of genetic mutations. In this study, a literature search from August 1985 to April 2013 was performed through the PubMed database using the keywords “genetic polymorphisms”, “prostate cancer” and “androgen deprivation therapy”. The results revealed that several genome-wide association studies (such as rs16901979, rs7931342, HSD17B4, rs6162 in the CYP17A1, rs4243229 and rs7201637 in the HSD17B2, rs1062577 in the ESR1, SLCO1B3, SLCO2B1, rs2939244 in the ARRDC3, rs9508016 in the FLT1, rs6504145 in the SKAP1, rs7830611 in the FBXO32, rs9508016 in the FLT1, rs12529 in the AKR1C3, rs16934641 in the BNC2, rs3763763 in the TACC2, rs2051778 in the ALPK1, and rs3763763 in the TACC2, AR, ESR1, and ESR2 and single-nucleotide polymorphisms in important pathways (such as androgen signal, biosynthesis, metabolism, androgen receptor binding site, response element, androgen receptor CAG repeat polymorphism length, and estrogen receptor-binding sites involved in prostate cancer occurrence and mechanism could serve as candidate biomarkers for the early detection of castration-resistant prostate cancer after androgen deprivation therapy. Additional investigations are required to decipher precisely the gene

  2. Exercise improves quality of life in androgen deprivation therapy-treated prostate cancer: systematic review of randomised controlled trials.

    Science.gov (United States)

    Teleni, Laisa; Chan, Raymond J; Chan, Alexandre; Isenring, Elisabeth A; Vela, Ian; Inder, Warrick J; McCarthy, Alexandra L

    2016-02-01

    Men receiving androgen deprivation therapy (ADT) for prostate cancer (PCa) are likely to develop metabolic conditions such as diabetes, cardiovascular disease, abdominal obesity and osteoporosis. Other treatment-related side effects adversely influence quality of life (QoL) including vasomotor distress, depression, anxiety, mood swings, poor sleep quality and compromised sexual function. The objective of this study was to systematically review the nature and effects of dietary and exercise interventions on QoL, androgen deprivation symptoms and metabolic risk factors in men with PCa undergoing ADT. An electronic search of CINAHL, CENTRAL, Medline, PsychINFO and reference lists was performed to identify peer-reviewed articles published between January 2004 and December 2014 in English. Eligible study designs included randomised controlled trials (RCTs) with pre- and post-intervention data. Data extraction and assessment of methodological quality with the Cochrane approach was conducted by two independent reviewers. Seven exercise studies were identified. Exercise significantly improved QoL, but showed no effect on metabolic risk factors (weight, waist circumference, lean or fat mass, blood pressure and lipid profile). Two dietary studies were identified, both of which tested soy supplements. Soy supplementation did not improve any outcomes. No dietary counselling studies were identified. No studies evaluated androgen-deficiency symptoms (libido, erectile function, sleep quality, mood swings, depression, anxiety and bone mineral density). Evidence from RCTs indicates that exercise enhances health- and disease-specific QoL in men with PCa undergoing ADT. Further studies are required to evaluate the effect of exercise and dietary interventions on QoL, androgen deprivation symptoms and metabolic risk factors in this cohort. © 2016 Society for Endocrinology.

  3. Androgen deprivation therapy for prostate cancer and the risk of hospitalisation for community-acquired pneumonia.

    Science.gov (United States)

    Hicks, Blánaid M; Yin, Hui; Bladou, Franck; Ernst, Pierre; Azoulay, Laurent

    2017-07-01

    Androgens have been shown to influence both the immune system and lung tissue, raising the hypothesis that androgen deprivation therapy (ADT) for prostate cancer may increase the risk of pneumonia. Thus, the aim of this study was to determine whether ADT is associated with an increased risk of hospitalisation for community-acquired pneumonia in patients with prostate cancer. This was a population-based cohort study using the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository. The cohort consisted of 20 310 men newly diagnosed with non-metastatic prostate cancer between 1 April 1998 and 31 March 2015. Time-dependent Cox proportional hazards models were used to estimate adjusted HRs and 95% CIs for hospitalisation for community-acquired pneumonia associated with current and past use of ADT compared with non-use. During a mean follow-up of 4.3 years, there were 621 incident hospitalisations for community-acquired pneumonia (incidence rate: 7.2/1000 person-years). Current ADT use was associated with an 81% increased risk of hospitalisation for community-acquired pneumonia (12.1 vs 3.8 per 1000 person-years, respectively; HR 1.81, 95% CI 1.47 to 2.23). The association was observed within the first six months of use (HR 1.73, 95% CI 1.23 to 2.42) and remained elevated with increasing durations of use (≥25 months; HR 1.79, 95% CI 1.39 to 2.30). In contrast, past ADT use was not associated with an increased risk (HR 1.23, 95% CI 0.95 to 1.60). The use of ADT is associated with an increased risk of hospitalisation for community-acquired pneumonia in men with prostate cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Impact of Androgen Deprivation Therapy on Self-reported Cognitive Function in Men with Prostate Cancer.

    Science.gov (United States)

    Marzouk, Shireen; Naglie, Gary; Tomlinson, George; Duff Canning, Sarah; Breunis, Henriette; Timilshina, Narhari; Alibhai, Shabbir M H

    2018-02-22

    Although androgen deprivation therapy (ADT) is widely used to treat prostate cancer (PC), its effects on cognitive function are unclear, and no prior report has examined the impact of ADT on self-reported cognitive function. Three groups of men age 50 or older and matched on age and education were enrolled: PC patients starting continuous ADT (n=81), PC patients not receiving ADT (PC controls, n=84), and healthy controls (n=85). Two scales from the Functional Assessment of Cancer Therapy-Cognitive Questionnaire (FACT-Cog) version 3 were used to assess self-reported cognitive function. Changes in cognitive scores over time were analyzed using two approaches: multivariable regression and calculation of the proportion of subjects per group with declines of 1-SD or more. Multivariable regression was used to assess predictors of decline in self-reported cognitive function. Relationships between the FACT-Cog and a neuropsychological battery of 15 tests were also examined. The mean age of participants was 69 years (range 50-87) and their mean educational level was 15 years (range 8-24). FACT-Cog scores were similar at baseline across cohorts. Neither analytic approach found ADT use to be associated with changes in self-reported cognitive function on either FACT-Cog scale. Mood and fatigue were correlated with changes in self-reported cognitive function. The relationship between self-reported and objective cognitive measures was weak (maximum Spearman correlation coefficient of 0.14) and only two of 30 correlations were statistically significant. Twelve months of ADT was not associated with self-reported cognitive function in older men with non-metastatic PC. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  5. Persistence of senescent prostate cancer cells following prolonged neoadjuvant androgen deprivation therapy.

    Directory of Open Access Journals (Sweden)

    Michael L Blute

    Full Text Available Androgen deprivation therapy (ADT commonly leads to incomplete cell death and the fate of persistent cells involves, in part, a senescent phenotype. Senescence is terminal growth arrest in response to cell stress that is characterized by increased lysosomal-β-galactosidase (GLB1 the origin of senescence associated-β-gal activity (SA-β-gal. In the current study senescence is examined in vivo after ADT use in a neoadjuvant trial.Tissue microarrays were generated from prostate cancer specimens (n = 126 from a multicenter neoadjuvant ADT trial. Arrays were subjected to multiplexed immunofluorescent staining for GLB1, Ki67, cleaved caspase 3 (CC3 and E-cadherin. Automated quantitative imaging was performed using Vectra™ and expression correlated with clinicopathologic features.Tissue was analyzed from 59 patients treated with neoadjuvant ADT and 67 receiving no therapy preoperatively. Median follow-up was 85.3 mo and median ADT treatment was 5 mo. In PC treated with neoadjuvant ADT, GLB1 expression increased in intermediate Gleason score (GS 6-7; p = 0.001, but not high grade (GS 8-10 cancer. Significantly higher levels of GLB1 were seen in tissues undergoing neoadjuvant ADT longer than 5 months compared to untreated tissues (p = 0.002. In contrast, apoptosis significantly increased earlier (1-4 mo after ADT treatment (p<0.5.Increased GLB1 after neoadjuvant ADT occurs primarily among more clinically favorable intermediate grade cancers and enrichment of the phenotype occurs in a temporally prolonged fashion. Senescence may explain the persistence of PCa cells after ADT. Given concerns for the detrimental longer term presence of senescent cells, targeting these cells for removal may improve outcomes.

  6. Prospective study of exercise intervention in prostate cancer patients on androgen deprivation therapy

    International Nuclear Information System (INIS)

    Beydoun, Nadine; Bucci, Joseph A.; Chin, Yaw S.; Spry, Nigel; Newton, Robert; Galvão, Daniel A.

    2014-01-01

    Androgen deprivation therapy (ADT) is an important component of modern prostate cancer treatment. Survival benefits from neo-adjuvant and adjuvant hormones may take years to manifest, and balancing this with potential morbidity of therapy can be challenging. This study aimed to assess whether education and short-term combined aerobic and resistance exercises could help to ameliorate the adverse side effects of ADT. Eight hundred fifty-nine patients with relapsed or metastatic prostate cancer on leuprorelin acetate were allocated to three interventional streams based on patient preference and medical fitness: supervised group (Face-to-Face) exercise sessions, home-based (At Home) exercise or a support programme for those incapable of exercising (Support). Patients enrolled onto Face to Face underwent measurement of body composition and cardiorespiratory fitness variables at baseline and programme completion. Patients in the exercise streams were surveyed to determine the programme's impact on physical fitness and well-being. Statistically significant improvements (p<0.001) were seen in all measured cardiorespiratory fitness and strength variables. Programme attrition rates were low (75/859; 8.7%), the primary reason for withdrawal being discontinuation of hormones (70%). Programme satisfaction was high, with 98% of surveyed patients reporting a positive impact on fitness and 97% planning to continue exercising after programme completion. At 6 months, improved physical and emotional well-being was reported by 93 and 79% of patients, respectively. A short-term structured exercise intervention results in high compliance and significant improvements in muscle strength and cardiorespiratory fitness in prostate cancer patients on ADT.

  7. National Trends and Predictors of Androgen Deprivation Therapy Use in Low-Risk Prostate Cancer.

    Science.gov (United States)

    Yang, David D; Muralidhar, Vinayak; Mahal, Brandon A; Labe, Shelby A; Nezolosky, Michelle D; Vastola, Marie E; King, Martin T; Martin, Neil E; Orio, Peter F; Choueiri, Toni K; Trinh, Quoc-Dien; Spratt, Daniel E; Hoffman, Karen E; Feng, Felix Y; Nguyen, Paul L

    2017-06-01

    Androgen deprivation therapy (ADT) is not recommended for low-risk prostate cancer because of its lack of benefit and potential for harm. We evaluated the incidence and predictors of ADT use in low-risk disease. Using the National Cancer Database, we identified 197,957 patients with low-risk prostate cancer (Gleason score of 3 + 3 = 6, prostate-specific antigen level used multiple logistic regression to evaluate predictors of ADT use and Cox regression to examine its association with all-cause mortality. Overall ADT use decreased from 17.6% in 2004 to 3.5% in 2012. In 2012, 11.5% of low-risk brachytherapy patients and 7.6% of external beam radiation therapy patients received ADT. Among 82,352 irradiation-managed patients, predictors of ADT use included treatment in a community versus academic cancer program (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.50-1.71; Puse versus external beam radiation therapy (AOR, 1.32; 95% CI, 1.27-1.37; Puse included a Charlson-Deyo comorbidity score of ≥2 versus 0 (AOR, 1.42; 95% CI, 1.06-1.91; P=.018); treatment in a community versus academic cancer program (AOR, 1.61; 95% CI, 1.37-1.90; Puse was associated with increased all-cause mortality in patients who did not receive local therapy (adjusted hazard ratio, 1.28; 95% CI, 1.14-1.43; Puse in low-risk prostate cancer has declined nationally but may remain an issue of concern in certain populations and regions. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Maximal exercise testing of men with prostate cancer being treated with androgen deprivation therapy.

    Science.gov (United States)

    Wall, Bradley A; Galvão, Daniel A; Fatehee, Naeem; Taaffe, Dennis R; Spry, Nigel; Joseph, David; Newton, Robert U

    2014-12-01

    Exercise is being increasingly established as a key adjuvant therapy in clinical oncology. As research has demonstrated the beneficial effect of exercise for cancer management, a growing number of patients with cancer are undertaking structured exercise programs. This study aimed to determine the safety and feasibility of formal exercise testing in clinical settings as it is becoming increasingly used as a screening tool and for exercise prescription purposes. One hundred and twelve patients with prostate cancer undergoing androgen deprivation therapy (ADT) took part in a physician-supervised multistage maximal stress test (Bruce protocol). Sixty patients had been on ADT for 3 months (chronic). Of these men, 85% were able to meet the criteria for the attainment of V˙O2max, whereas three positive tests (3.2%) were observed. The three participants who recorded a positive stress test underwent further medical examination and were subsequently cleared of clinically significant cardiovascular disease. Apart from the relatively low V˙O2max (24.7 ± 6.0 mL·kg·min, 10th-15th percentile), compared with normative data in healthy age-matched controls, the cardiovascular response to exercise was similar in this cancer population. Moreover, treatment duration did not seem to influence cardiovascular responses to exercise. This early evidence suggests that risk of adverse events during maximal exercise testing is relatively low in this population and certainly no higher than that in ages-matched, apparently healthy individuals. Maximal exercise testing was demonstrated to be feasible and safe, providing a direct assessment of V˙O2max. The relatively low number of positive tests in this study suggests that the risk of adverse events is relatively low in this population and certainly no higher than that in age-matched, apparently healthy individuals.

  9. Adjuvant and salvage therapy following radical prostatectomy for prostate cancer: effect of combined transient androgen deprivation and irradiation

    International Nuclear Information System (INIS)

    Eulau, Stephen M.; Tate, David J.; Cox, Richard S.; Bagshaw, Malcolm A.; Hancock, Steven L.

    1996-01-01

    Purpose: Adjuvant and salvage irradiation have been shown to improve local control after radical prostatectomy for prostatic cancer in patients with high risk pathologic features, rising PSA, or evidence of local failure. Transient androgen deprivation combined with primary irradiation has resulted in improved local control and biochemical disease free survival in patients with locally advanced, unresected, prostate cancer. This retrospective study evaluates whether transient androgen blockade improves the outcome from post-prostatectomy irradiation given as either adjuvant or salvage therapy. Methods: From August, 1985 to December, 1995, 105 patients were treated with radiotherapy to the prostatic fossa following radical prostatectomy for adenocarcinoma of the prostate. No patient had clinically or radiographically evident distant disease. Median follow-up was 4.6 years from the date of surgery and 3.2 years from completion of radiotherapy. Findings at prostatectomy included capsular penetration in 38 patients, seminal vesicle involvement in 42 patients, lymph node involvement in 15 patients, and positive surgical margins in 70 patients. Treatment was administered as adjuvant therapy for high risk pathologic features in 39 patients, for persistent or rising PSA in 52 patients, or for clinically evident local recurrence in 14 patients. Of the 105 patients, 32 received combined androgen deprivation/radiotherapy and 73 received radiotherapy alone. Both groups received 60-70 Gy in 2 Gy daily fractions to the prostatic fossa. Selected patients with poor prognostic features received pelvic irradiation to a median dose of 50 Gy. Androgen deprivation typically consisted of Lupron and Flutamide for 4 to 6 months before, during, and in selected cases, after irradiation. No patients received maintenance androgen deprivation or underwent orchiectomy. Tumor stage, lymph node status, Gleason sum, and indications for treatment did not differ significantly between the two groups

  10. Endurance training improves insulin sensitivity and body composition in prostate cancer patients treated with androgen deprivation therapy

    DEFF Research Database (Denmark)

    Hvid, Thine; Winding, Kamilla; Rinnov, Anders

    2013-01-01

    Insulin resistance and changes in body composition are side effects of androgen deprivation therapy (ADT) given to prostate cancer patients. The present study investigated whether endurance training improves insulin sensitivity and body composition in ADT-treated prostate cancer patients. Nine men...... and magnetic resonance imaging). The secondary endpoint was systemic inflammation. Statistical analysis was carried out using two-way ANOVA. Endurance training increased VO2max (ml(O2)/min per kg) by 11 and 13% in the patients and controls respectively (P...

  11. Risk factors for bone loss with prostate cancer in Korean men not receiving androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Sun-Ouck Kim

    2009-04-01

    Full Text Available PURPOSE: Preexisting bone loss in men with prostate cancer is an important issue due to the accelerated bone loss during androgen deprivation therapy (ADT. In addition, a high prostate-specific antigen (PSA level has been reported to be related to bone metabolism. This study assessed the factors associated with osteoporosis in Korean men with non-metastatic prostate cancer before undergoing ADT. MATERIAL AND METHODS: The study enrolled patients admitted for a prostate biopsy because of a high PSA or palpable nodule on a digital rectal examination. We divided the patients (n = 172 according to the results of the biopsy: group I, non-metastatic prostate cancer (n = 42 and group II, benign prostatic hypertrophy (BPH; n = 130. The lumbar bone mineral density (BMD was evaluated using quantitative computed tomography. The demographic, health status, lifestyle, body mass index (BMI, serum testosterone concentration, and disease variables in prostate cancer (Gleason score, clinical stage, and PSA were analyzed prospectively to determine their effect on the BMD. RESULTS: The estimated mean T-score was higher in group I than in group II (-1.96 ± 3.35 vs. -2.66 ± 3.20, but without statistic significance (p = 0.235. The significant factors correlated with BMD in group I were a high serum PSA (ß = -0.346, p = 0.010 and low BMI (ß = 0.345, p = 0.014 in the multiple linear regression model. Also old age (r = -0.481, p = 0.001, a high serum PSA (r = -0.571, p < 0.001, low BMI (r = 0.598, p < 0.001, and a high Gleason’s score (r = -0.319, p = 0.040 were the factors related to BMD in the correlation. The significant factors correlated with BMD in group II were old age (ß = -0.324, p = 0.001 and BMI (ß = 0.143, p = 0.014 in the multiple linear regression model. CONCLUSIONS: The risk factors for osteoporosis in men with prostate cancer include a low BMI, and elevated serum PSA. Monitoring BMD from the outset of ADT is a logical first step in the clinical

  12. Implementation of High-Dose-Rate Brachytherapy and Androgen Deprivation in Patients With Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lilleby, Wolfgang, E-mail: wolfgang.lilleby@ous-hf.no [Cancer Clinic, Oslo University Hospital, Norwegian Radiumhospital, Department of Radiotherapy and Oncology, Oslo (Norway); Tafjord, Gunnar; Raabe, Nils K. [Cancer Clinic, Oslo University Hospital, Norwegian Radiumhospital, Department of Radiotherapy and Oncology, Oslo (Norway)

    2012-07-01

    Purpose: To evaluate outcome (overall survival [OS], the actuarial 5-year cancer-specific survival [CSS], disease-free survival [DFS], biochemical failure-free survival [BFS]), complications and morbidity in patients treated with high-dose-rate brachytherapy (HDR-BT) boost and hormonal treatment with curative aims. Methods: Between 2004 and 2009, 275 prospectively followed pN0/N0M0 patients were included: 19 patients (7%) with T2, Gleason score 7 and prostate-specific antigen (PSA) <10 and 256 patients (93%) with T3 or Gleason score 8-10 or PSA >20 received multimodal treatment with conformal four-field radiotherapy (prostate/vesiculae 2 Gy Multiplication-Sign 25) combined with HDR-BT (iridium 192; prostate 10 Gy Multiplication-Sign 2) with long-term androgen deprivation therapy (ADT). Results: After a median observation time of 44.2 months (range, 10.4-90.5 months) 12 patients had relapsed clinically and/or biochemically and 10 patients were dead, of which 2 patients died from prostate cancer. Five-year estimates of BFS, CSS, DFS, and OS rates were 98.5%, 99.3%, 95.6%, and 96.3%, respectively. None of the patients with either Gleason score <8 or with intermediate risk profile had relapsed. The number of HDR-BT treatments was not related to outcome. Despite of age (median, 65.7 years; range, 45.7-77 years) and considerable pretreatment comorbidity in 39 of 275 patients, Genitourinary treatment-related morbidity was moderate with long-lasting Radiation Therapy Oncology Group Grade 2 voiding problems in 26 patients (9.5%) and occasionally mucous discharge in 20 patients (7%), none with Grade >2 for gastrointestinal at follow-up. Complications during implantations were related to pubic arch interference (4 patients) and lithotomy time, causing 2 patients to develop compartment syndrome. Conclusion: Despite still preliminary observations, our 5-year outcome estimates favor the implementation of high-dose-rate brachytherapy in high-risk patients combined with conformal

  13. A pilot study of exercise in men with prostate cancer receiving androgen deprivation therapy

    International Nuclear Information System (INIS)

    Lee, C Ellen; Leslie, William D; Lau, YK James

    2012-01-01

    Androgen deprivation therapy (ADT) is the mainstay therapy for men with prostate cancer. However, there are musculoskeletal side effects from ADT that increase the risk for osteoporosis and fracture, and can compromise the quality of life of these individuals. The objectives of this study are to determine the efficacy of a home-based walking exercise program in promoting bone health, physical function and quality of life in men with prostate cancer receiving ADT. A 12-month prospective, single-blinded, randomized controlled trial will be conducted to compare the Exercise Group with the Control Group. Sixty men with prostate cancer who will be starting ADT will be recruited and randomly assigned to one of the two groups: the Exercise Group will receive instructions in setting up an individualized 12-month home-based walking exercise program, while the Control Group will receive standard medical advice from the attending physician. A number of outcome measures will be used to assess bone health, physical function, and health-related quality of life. At baseline and 12 months, bone health will be assessed using dual-energy X-ray absorptiometry. At baseline and every 3 months up to 12 months, physical function will be evaluated using the Functional Assessment of Chronic Illness Therapy - Fatigue Scale, Activities-specific Balance Confidence Scale, Short Physical Performance Battery, and Six-Minute Walk Test; and health-related quality of life will be assessed using the Functional Assessment of Cancer Therapy Prostate Module and the Medical Outcomes Study 12-item Short Form Health Survey Version 2. A mixed multiple analysis of variance will be used to analyze the data. Musculoskeletal health management remains a challenge in men with prostate cancer receiving ADT. This study addresses this issue by designing a simple and accessible home-based walking exercise program that will potentially have significant impact on reducing the risk of fracture, promoting physical

  14. High-Dose Adjuvant Radiotherapy After Radical Prostatectomy With or Without Androgen Deprivation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ost, Piet, E-mail: piet.ost@ugent.be [Department of Radiotherapy, Ghent University Hospital (Belgium); Cozzarini, Cesare [Department of Radiotherapy, Hospital San Raffaele, Milan (Italy); De Meerleer, Gert [Department of Radiotherapy, Ghent University Hospital (Belgium); Fiorino, Claudio [Department of Radiotherapy, Hospital San Raffaele, Milan (Italy); De Potter, Bruno [Department of Radiotherapy, Ghent University Hospital (Belgium); Briganti, Alberto [Department of Urology, San Raffaele Hospital, Vita-Salute University, Milan (Italy); Nagler, Evi V.T. [Department of Nephrology, Ghent University Hospital (Belgium); Montorsi, Francesco [Department of Urology, San Raffaele Hospital, Vita-Salute University, Milan (Italy); Fonteyne, Valerie [Department of Radiotherapy, Ghent University Hospital (Belgium); Di Muzio, Nadia [Department of Radiotherapy, Hospital San Raffaele, Milan (Italy)

    2012-07-01

    Purpose: To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (>69 Gy) adjuvant radiotherapy (HD-ART) and the impact of androgen deprivation therapy (ADT). Methods and Materials: Between 1999 and 2008, 225 node-negative patients were referred for HD-ART with or without ADT to two large academic institutions. Indications for HD-ART were extracapsular extension, seminal vesicle invasion (SVI), and/or positive surgical margins at radical prostatectomy (RP). A dose of at least 69.1 Gy was prescribed to the prostate bed and seminal vesicle bed. The ADT consisted of a luteinizing hormone-releasing hormone analog. The duration and indication of ADT was left at the discretion of the treating physician. The effect of HD-ART and ADT on biochemical (bRFS) and clinical (cRFS) relapse-free survival was examined through univariate and multivariate analysis, with correction for known patient- and treatment-related variables. Interaction terms were introduced to evaluate effect modification. Results: After a median follow-up time of 5 years, the 7-year bRFS and cRFS were 84% and 88%, respectively. On multivariate analysis, the addition of ADT was independently associated with an improved bRFS (hazard ratio [HR] 0.4, p = 0.02) and cRFS (HR 0.2, p = 0.008). Higher Gleason scores and SVI were associated with decreased bRFS and cRFS. A lymphadenectomy at the time of RP independently improved cRFS (HR 0.09, p = 0.009). The 7-year probability of late Grade 2-3 toxicity was 29% and 5% for genitourinary (GU) and gastrointestinal (GI) symptoms, respectively. The absolute incidence of Grade 3 toxicity was <1% and 10% for GI and GU symptoms, respectively. The study is limited by its retrospective design and the lack of a standardized use of ADT. Conclusions: This retrospective study shows significantly improved bRFS and cRFS rates with the addition of ADT to HD-ART, with low Grade 3 gastrointestinal toxicity and 10% Grade 3 genitourinary toxicity.

  15. National Trends and Predictors of Androgen Deprivation Therapy Use in Low-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, David D. [Harvard Medical School, Boston, Massachusetts (United States); Muralidhar, Vinayak [Department of Medicine, Harvard Medical School, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Mahal, Brandon A. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Labe, Shelby A.; Nezolosky, Michelle D.; Vastola, Marie E.; King, Martin T.; Martin, Neil E.; Orio, Peter F. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Choueiri, Toni K. [Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Trinh, Quoc-Dien [Division of Urological Surgery, Harvard Medical School, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Spratt, Daniel E. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); University of Michigan, Ann Arbor, Michigan (United States); Hoffman, Karen E. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Feng, Felix Y. [Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts (United States); Departments of Urology & Medicine and Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California (United States); and others

    2017-06-01

    Purpose: Androgen deprivation therapy (ADT) is not recommended for low-risk prostate cancer because of its lack of benefit and potential for harm. We evaluated the incidence and predictors of ADT use in low-risk disease. Methods and Materials: Using the National Cancer Database, we identified 197,957 patients with low-risk prostate cancer (Gleason score of 3 + 3 = 6, prostate-specific antigen level <10 ng/mL, and cT1-T2a) diagnosed from 2004 to 2012 with complete demographic and treatment information. We used multiple logistic regression to evaluate predictors of ADT use and Cox regression to examine its association with all-cause mortality. Results: Overall ADT use decreased from 17.6% in 2004 to 3.5% in 2012. In 2012, 11.5% of low-risk brachytherapy patients and 7.6% of external beam radiation therapy patients received ADT. Among 82,352 irradiation-managed patients, predictors of ADT use included treatment in a community versus academic cancer program (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.50-1.71; P<.001; incidence, 14.0% vs 6.0% in 2012); treatment in the South (AOR, 1.51), Midwest (AOR, 1.81), or Northeast (AOR, 1.90) versus West (P<.001); and brachytherapy use versus external beam radiation therapy (AOR, 1.32; 95% CI, 1.27-1.37; P<.001). Among 25,196 patients who did not receive local therapy, predictors of primary ADT use included a Charlson-Deyo comorbidity score of ≥2 versus 0 (AOR, 1.42; 95% CI, 1.06-1.91; P=.018); treatment in a community versus academic cancer program (AOR, 1.61; 95% CI, 1.37-1.90; P<.001); and treatment in the South (AOR, 1.26), Midwest (AOR, 1.52), or Northeast (AOR, 1.28) versus West (P≤.008). Primary ADT use was associated with increased all-cause mortality in patients who did not receive local therapy (adjusted hazard ratio, 1.28; 95% CI, 1.14-1.43; P<.001) after adjustment for age and comorbidity. Conclusions: ADT use in low-risk prostate cancer has declined nationally but may remain an issue

  16. Androgen deprivation therapy's impact on the mood of prostate cancer patients as perceived by patients and the partners of patients.

    Science.gov (United States)

    Van Dam, Dexter; Wassersug, Richard J; Hamilton, Lisa Dawn

    2016-07-01

    To assess the relationship between of androgen deprivation therapy (ADT) and the mood of prostate cancer (PCa) patients and partners of PCa patients. PCa patients (n = 295) and partners of patients (n = 84) completed an online survey assessing the patients' current mood and mood prior to treatment, relationship adjustment, and sexual function. We compared men on ADT to men who received non-hormonal treatments for their PCa. Patients currently treated with ADT (n = 82) reported worsened mood as measured by the Profile of Mood States compared to those not on ADT (n = 213). The negative impact of ADT on mood, however, was reduced in older patients. Partners of patients on ADT (n = 42) reported similar declines in the patient's mood that patients reported, but to a greater degree than patient-reported levels. Our data support ADT's impact on PCa patients' mood and verify that partners concurrently see the effects. The psychological changes related to ADT can impact relationships and affect the quality of life of both PCa patients and partners. Patients and their partners are likely to benefit from being well informed about the psychological effects of androgen deprivation on men beginning ADT. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Significance of pretreatment cardiovascular morbidity as a risk factor during treatment with parenteral oestrogen or combined androgen deprivation of 915 patients with metastasized prostate cancer

    DEFF Research Database (Denmark)

    Johansson, Robert; Damber, Jan Erik; Hagerman, Inger

    2011-01-01

    This study aimed to evaluate prognostic risk factors for cardiovascular events during treatment of metastatic prostate cancer patients with high-dose parenteral polyoestradiol phosphate (PEP, Estradurin®) or combined androgen deprivation (CAD) with special emphasis on pretreatment cardiovascular...... disease....

  18. Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer: part 2. Final evaluation of the Scandinavian Prostatic Cancer Group (SPCG) Study No. 5

    DEFF Research Database (Denmark)

    Hedlund, P.O.; Damber, J.E.; Hagerman, I.

    2008-01-01

    To compare parenteral estrogen therapy in the form of high-dose polyestradiol phosphate (PEP; Estradurin) with combined androgen deprivation (CAD) in the treatment of prostate cancer patients with skeletal metastases. The aim of the study was to compare anticancer efficacy and adverse events...

  19. Type I Collagen Synthesis Marker Procollagen I N-Terminal Peptide (PINP) in Prostate Cancer Patients Undergoing Intermittent Androgen Suppression

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, Gerhard, E-mail: gerhard.hamilton@toc.lbg.ac.at; Olszewski-Hamilton, Ulrike [Ludwig Boltzmann Cluster of Translational of Oncology, Nussdorfer Strasse 64, Vienna A-1090 (Austria); Theyer, Gerhard [Hospital Kittsee, Kittsee A-2421, Burgenland (Austria)

    2011-09-15

    Intermittent androgen suppression (IAS) therapy for prostate cancer patients attempts to maintain the hormone dependence of the tumor cells by cycles alternating between androgen suppression (AS) and treatment cessation till a certain prostate-specific antigen (PSA) threshold is reached. Side effects are expected to be reduced, compared to standard continuous androgen suppression (CAS) therapy. The present study examined the effect of IAS on bone metabolism by determinations of serum procollagen I N-terminal peptide (PINP), a biochemical marker of collagen synthesis. A total of 105 treatment cycles of 58 patients with prostate cancer stages ≥pT2 was studied assessing testosterone, PSA and PINP levels at monthly intervals. During phases of AS lasting for up to nine months PSA levels were reversibly reduced, indicating apoptotic regression of the prostatic tumors. Within the first cycle PINP increased at the end of the AS period and peaked in the treatment cessation phase. During the following two cycles a similar pattern was observed for PINP, except a break in collagen synthesis as indicated by low PINP levels in the first months off treatment. Therefore, measurements of the serum PINP concentration indicated increased bone matrix synthesis in response to >6 months of AS, which uninterruptedly continued into the first treatment cessation phase, with a break into each of the following two pauses. In summary, synthesis of bone matrix collagen increases while degradation decreases during off-treatment phases in patients undergoing IAS. Although a direct relationship between bone matrix turnover and risk of fractures is difficult to establish, IAS for treatment of biochemical progression of prostate tumors is expected to reduce osteoporosis in elderly men often at high risk for bone fractures representing a highly suitable patient population for this kind of therapy.

  20. Associations between statin use and progression in men with prostate cancer treated with primary androgen deprivation therapy

    DEFF Research Database (Denmark)

    Mikkelsen, Marta Kramer; Thomsen, Frederik Birkebæk; Berg, Kasper Drimer

    2017-01-01

    INTRODUCTION: In several observational studies, statin use has been associated with reduced risk of progression and mortality in men with prostate cancer (PCa). The study aim was to investigate the association between statin use at time of PCa diagnosis and time to PCa progression in men...... with advanced or metastatic PCa receiving androgen deprivation therapy (ADT) as primary treatment. PATIENTS AND METHODS: The study population consisted of all men receiving ADT as primary therapy at two Danish Urological Departments in 2007-2013. The primary outcome was time to progression defined as castration...... between statin use and risk of progression, HR 0.98 (95% CI: 0.72-1.32). In competing risk analyses the 5-year cumulative incidence of progression was 55% (95% CI: 46-64%) for statin users and 62% (95% CI: 57-67%) for non-statin users, p = 0.11. CONCLUSION: In the current study, statin use at time of PCa...

  1. Androgen Deprivation Enhances PLZF-Repressed Cistrome that Promotes the Castration-Resistant Phenotype

    Science.gov (United States)

    2014-10-01

    regulated network is activated when AR binds enhancer elements and modulates specific enhancer–promoter looping. Kallikrein-related peptidase 3 (KLK3... peptidase 3 (KLK3) enhancer, one of the strongest AR-bound enhancers in prostate cancer cells, produces KLK3 eRNA (KLK3e), which impacts androgen

  2. A randomized controlled trial on the effectiveness of strength training on clinical and muscle cellular outcomes in patients with prostate cancer during androgen deprivation therapy: rationale and design.

    Science.gov (United States)

    Thorsen, Lene; Nilsen, Tormod S; Raastad, Truls; Courneya, Kerry S; Skovlund, Eva; Fosså, Sophie D

    2012-03-29

    Studies indicate that strength training has beneficial effects on clinical health outcomes in prostate cancer patients during androgen deprivation therapy. However, randomized controlled trials are needed to scientifically determine the effectiveness of strength training on the muscle cell level. Furthermore, close examination of the feasibility of a high-load strength training program is warranted. The Physical Exercise and Prostate Cancer (PEPC) trial is designed to determine the effectiveness of strength training on clinical and muscle cellular outcomes in non-metastatic prostate cancer patients after high-dose radiotherapy and during ongoing androgen deprivation therapy. Patients receiving androgen deprivation therapy for 9-36 months combined with external high-dose radiotherapy for locally advanced prostate cancer are randomized to an exercise intervention group that receives a 16 week high-load strength training program or a control group that is encouraged to maintain their habitual activity level. In both arms, androgen deprivation therapy is continued until the end of the intervention period.Clinical outcomes are body composition (lean body mass, bone mineral density and fat mass) measured by Dual-energy X-ray Absorptiometry, serological outcomes, physical functioning (muscle strength and cardio-respiratory fitness) assessed with physical tests and psycho-social functioning (mental health, fatigue and health-related quality of life) assessed by questionnaires. Muscle cellular outcomes are a) muscle fiber size b) regulators of muscle fiber size (number of myonuclei per muscle fiber, number of satellite cells per muscle fiber, number of satellite cells and myonuclei positive for androgen receptors and proteins involved in muscle protein degradation and muscle hypertrophy) and c) regulators of muscle fiber function such as proteins involved in cellular stress and mitochondrial function. Muscle cellular outcomes are measured on muscle cross sections and muscle

  3. A randomized controlled trial on the effectiveness of strength training on clinical and muscle cellular outcomes in patients with prostate cancer during androgen deprivation therapy: rationale and design

    Directory of Open Access Journals (Sweden)

    Thorsen Lene

    2012-03-01

    Full Text Available Abstract Background Studies indicate that strength training has beneficial effects on clinical health outcomes in prostate cancer patients during androgen deprivation therapy. However, randomized controlled trials are needed to scientifically determine the effectiveness of strength training on the muscle cell level. Furthermore, close examination of the feasibility of a high-load strength training program is warranted. The Physical Exercise and Prostate Cancer (PEPC trial is designed to determine the effectiveness of strength training on clinical and muscle cellular outcomes in non-metastatic prostate cancer patients after high-dose radiotherapy and during ongoing androgen deprivation therapy. Methods/design Patients receiving androgen deprivation therapy for 9-36 months combined with external high-dose radiotherapy for locally advanced prostate cancer are randomized to an exercise intervention group that receives a 16 week high-load strength training program or a control group that is encouraged to maintain their habitual activity level. In both arms, androgen deprivation therapy is continued until the end of the intervention period. Clinical outcomes are body composition (lean body mass, bone mineral density and fat mass measured by Dual-energy X-ray Absorptiometry, serological outcomes, physical functioning (muscle strength and cardio-respiratory fitness assessed with physical tests and psycho-social functioning (mental health, fatigue and health-related quality of life assessed by questionnaires. Muscle cellular outcomes are a muscle fiber size b regulators of muscle fiber size (number of myonuclei per muscle fiber, number of satellite cells per muscle fiber, number of satellite cells and myonuclei positive for androgen receptors and proteins involved in muscle protein degradation and muscle hypertrophy and c regulators of muscle fiber function such as proteins involved in cellular stress and mitochondrial function. Muscle cellular outcomes

  4. Nutrition therapy with high intensity interval training to improve prostate cancer-related fatigue in men on androgen deprivation therapy: a study protocol

    OpenAIRE

    Baguley, Brenton J.; Skinner, Tina L.; Leveritt, Michael D.; Wright, Olivia R. L.

    2017-01-01

    Background Cancer-related fatigue is one of the most prevalent, prolonged and distressing side effects of prostate cancer treatment with androgen deprivation therapy. Preliminary evidence suggests natural therapies such as nutrition therapy and structured exercise prescription can reduce symptoms of cancer-related fatigue. Men appear to change their habitual dietary patterns after prostate cancer diagnosis, yet prostate-specific dietary guidelines provide limited support for managing adverse ...

  5. Androgen-deprivation therapy-induced aggressive prostate cancer with neuroendocrine differentiation

    Directory of Open Access Journals (Sweden)

    Julia Lipianskaya

    2014-08-01

    Full Text Available Most prostate cancers (PCas are classified as acinar type (conventional adenocarcinoma which are composed of tumor cells with luminal differentiation including the expression of androgen receptor (AR and prostate-specific antigen (PSA. There are also scattered neuroendocrine (NE cells in every case of adenocarcinoma. The NE cells are quiesecent, do not express AR or PSA, and their function remains unclear. We have demonstrated that IL8-CXCR2-P53 pathway provides a growth-inhibitory signal and keeps the NE cells in benign prostate and adenocarcinoma quiescent. Interestingly, some patients with a history of adenocarcinoma recur with small cell neuroendocrine carcinoma (SCNC after hormonal therapy, and such tumors are composed of pure NE cells that are highly proliferative and aggressive, due to P53 mutation and inactivation of the IL8-CXCR2-P53 pathway. The incidence of SCNC will likely increase due to the widespread use of novel drugs that further inhibit AR function or intratumoral androgen synthesis. A phase II trial has demonstrated that platinum-based chemotherapy may be useful for such therapy-induced tumors.

  6. Long-term side-effects of intermittent androgen suppression therapy in prostate cancer: results of a phase II study.

    Science.gov (United States)

    Malone, Shawn; Perry, Gad; Segal, Roanne; Dahrouge, Simone; Crook, Juanita

    2005-09-01

    To assess the feasibility and tolerability of intermittent androgen suppression therapy (IAS) in prostate cancer. Patients with recurrent or metastic prostate cancer received cyclical periods of treatment with leuprolide acetate and nilutamide for 8 months, and rest periods. Cycles were repeated at progression until the treatment failed to achieve normal prostate-specific antigen (PSA) levels. Patients were followed with PSA level, testosterone level, haemoglobin level, weight and bone mineral density evaluations. The median time to treatment failure, recovery from anaemia, or normalization of testosterone level was estimated by the Kaplan-Meier method. In all, 95 patients received 245 cycles; the median duration of rest periods was 8 months and median time to treatment failure 47 months. Testosterone recovery during rest periods was documented in 117 (61%) of cycles. Anaemia was mild and reported in 33%, 44% and 67% of cycles 1, 2 and 3, respectively. Sexual function recovered during the rest periods in 47% of cycles. There was no significant overall change in body mass index at the end of the treatment period. Osteoporosis was documented in at least one site evaluated in 41 patients (37%). IAS has the potential to reduce side-effects, including recovery of haemoglobin level, return of sexual function and absence of weight gain at the end of the study period.

  7. The effect of estrogen on the sexual interest of castrated males: Implications to prostate cancer patients on androgen-deprivation therapy.

    Science.gov (United States)

    Wibowo, Erik; Wassersug, Richard J

    2013-09-01

    Androgen deprivation therapy (ADT) for prostate cancer (PCa) treatment causes sexual dysfunction. We review here the effects of estrogen on the sexual performance of androgen-deprived males. The major findings are: 1. Estrogen receptors are present in brain centers that are important for sexual behavior; as well as in male reproductive organs, in a pattern suggesting that estrogen may have some role in orgasmic function and genital skin sensitivity. 2. Estrogen restores sexual interest above castrate levels in many vertebrates including reptiles, birds and mammals; but multiple factors contribute to the magnitude of this effect. 3. Data from castrated men, aromatase-deficient men, male-to-female transsexuals, and men on antiandrogens all suggest that estrogen can maintain some libido in androgen-deprived men. We discuss the general benefits of estrogen therapy to quality of life of men on ADT, the potential risks of this treatment, and possible treatment regimes for estrogen therapy in males. Unless contraindicated, we propose that PCa patients on ADT would benefit from supplemental parenteral estrogen. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Measurements of free and total PSA, tissue polypeptide-specific antigen (TPS), and CYFRA 21-1 in prostate cancer patients under intermittent androgen suppression therapy.

    Science.gov (United States)

    Theyer, G; Dürer, A; Theyer, U; Haberl, I; Ulsperger, E; Baumgartner, G; Hamilton, G

    1999-10-01

    The present study evaluated monthly measurements of free and total prostate-specific antigen (PSA), and the tumor proliferation markers tissue polypeptide-specific antigen (TPS) and cytokeratin fragment 21-1 (CYFRA 21-1) in patients with advanced prostate cancer receiving intermittent androgen suppression therapy (IAS). Thirty-four men received alternating cycles of 8 month androgen suppression and treatment cessation (mean duration, 10.3 months) until PSA increased to >20 microg/l. Measurements of testosterone, percentage of free PSA, TPS, and CYFRA 21-1 were performed using ELISA and RIA assays. Periods of androgen suppression resulted in reversible reductions of testosterone (from 6 +/- 0.8 to IAS cycle. TPS showed a decrease of 50% after 3 months, and CYFRA 21-1 a 25% decrease after 7 months of androgen suppression treatment. During treatment cessation, TPS exceeded the normal cutoff value of 90 U/l late in tumor regrowth (9-11 months), whereas CYFRA 21-1 remained below the normal cutoff value of 3.3 ng/ml. PSA is the best and most sensitive marker of prostate cancer regression and regrowth during IAS cycles of the markers tested in this study. Free PSA constitutes approximately 15% of total PSA (range, 5-32%), and its percentage showed no significant change during IAS cycles. The TPS and CYFRA 21-1 proliferation marker changes in IAS seem to be related mainly to effects on normal androgen-dependent tissues. Copyright 1999 Wiley-Liss, Inc.

  9. Optimal duration of androgen deprivation therapy following radiation therapy in intermediate- or high-risk non-metastatic prostate cancer: a systematic review and meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Leal, Frederico; Figueiredo, Maximiliano Augusto Novis de; Sasse, Andre Deeke, E-mail: sasse@cevon.com.br [Universidade Estadual de Campinas (UNICAMP), SP (Brazil)

    2015-05-15

    Objectives: to investigate current evidence on the optimal duration of adjuvant hormone deprivation for prostate cancer treated with radiation therapy with curative intent. Materials and Methods: A systematic search was performed in electronic databases. Data from randomized trials comparing different durations of hormone blockade was collected for pooled analysis. Overall survival, disease-free survival, disease-specific survival and toxicity were the outcomes of interest. Meta-analyses were performed using random-effects model. Results: Six studies met the eligibility criteria. For overall survival, the pooled data from the studies demonstrated a statistically significant benefit for longer hormone deprivation (Hazard Ratio 0.84; 95% CI 0.74 - 0.96). A statistically significant benefit was also found for disease-free survival (Hazard Ratio 0.74; 95% CI 0.62 - 0.89), and disease-specific survival (Hazard Ratio 0.73; 95% CI 0.62 - 0.85). Studies with longer blockade duration arm demonstrated greater benefit. Toxicity was low, with no increase in cardiovascular events. Conclusions: Longer duration of androgen deprivation combined to radiotherapy prolongs OS, DFS and DSS in patients with intermediate and high-risk non-metastatic prostate cancer. However, this evidence is based on trials using older radiation techniques, and further research of combination of androgen deprivation and new RT technologies may be warranted. (author)

  10. National survey addressing the information needs of primary care physicians: Side effect management of patients on androgen deprivation therapy.

    Science.gov (United States)

    Soeyonggo, Tony; Locke, Jennifer; Giudice, Maria Elizabeth Del; Alibhai, Shabbir; Fleshner, Neil Eric; Warde, Padraig

    2014-03-01

    Androgen deprivation therapy (ADT) is a common treatment for prostate cancer with numerous side effects. We assess primary care physicians' (PCPs) knowledge of ADT side effects and their interest in increasing their knowledge in this area. A list of active Canadian PCPs was obtained using the Canadian Medical Directory. A cross-sectional survey was distributed to 600 randomly selected physicians. We collected PCPs' demographic information, experience with ADT management, knowledge regarding ADT side effects and desired sources for obtaining knowledge on ADT management. In total, we received 103 completed questionnaires. Of these, 89% of PCPs had patients on ADT. One-third of respondents prescribed ADT and over half of them administered ADT annually. Thirty-eight percent felt their knowledge of ADT side effects was inadequate and 50% felt uncomfortable counselling patients on ADT. Many PCPs were less familiar with the incidence of functional side effects of ADT (i.e., hot flashes, fatigue and erectile dysfunction) compared to life-threatening side effects (i.e., cardiovascular events, metabolic syndrome, fractures). In terms of increasing their knowledge of ADT side effects, 82% of PCPs would use educational resources if they were available (52% and 32% preferred continued medical education [CME] events and educational pamphlets, respectively). PCPs play an important role in managing ADT side effects. There is poor awareness of the prevalence of ADT side effects, and many are uncomfortable in managing these side effects. These areas may be addressed through CME programs and educational pamphlets.

  11. Predictors of Fracture Risk and Bone Mineral Density in Men with Prostate Cancer on Androgen Deprivation Therapy

    Directory of Open Access Journals (Sweden)

    Katherine Neubecker

    2011-01-01

    Full Text Available Decrease of bone mineral density (BMD and fracture risk is increased in men with prostate cancer receiving androgen deprivation therapy (ADT. We looked at possible predictors of decreased BMD and increased fracture risk in men with prostate cancer; most of whom were on ADT. In a retrospective study, we analyzed serum, BMD, and clinical risk factors used in the Fracture Risk Assessment (FRAX tool and others in 78 men with prostate cancer with reported height loss. The subjects were divided in two groups: 22 men with and 56 without vertebral fractures. 17 of the 22 men with vertebral fractures on spine X-rays did not know they had a vertebral fracture. Of those 17 men, 9 had not previously qualified for treatment based on preradiograph FRAX score calculated with BMD, and 6 based on FRAX calculated without BMD. Performing spine films increased the predictive ability of FRAX for vertebral fracture. Vertebral fracture was better predicted by FRAX for other osteoporotic fractures than FRAX for hip fractures. The inclusion of BMD in FRAX calculations did not affect the predictive ability of FRAX. The PSA level showed a positive correlation with lumbar spine BMD and accounted for about 9% of spine BMD.

  12. Multimodal therapy for locally advanced prostate cancer: the roles of radiotherapy, androgen deprivation therapy, and their combination

    International Nuclear Information System (INIS)

    Lee, Sung Uk; Cho, Kwan Ho

    2017-01-01

    Locally advanced prostate cancer (LAPC) is defined as histologically proven T3–4 prostatic adenocarcinoma. In this review, we define the individual roles of radiotherapy (RT), short-term (ST-) and long-term (LT-) androgen deprivation therapy (ADT), and their combination in multimodal therapy for LAPC. Despite limitations in comparing the clinical outcomes among published papers, in the present study, a trend of 10-year clinical outcomes was roughly estimated by calculating the average rates weighted by the cohort number. With RT alone, the following rates were estimated: 87% biochemical failure, 34% local failure (LF), 48% distant metastasis (DM), 38% overall survival (OS), and 27% disease-specific mortality (DSM). Those associated with ADT alone were 74% BCF, 54% OS, and 25% DSM, which appeared to be better than those of RT alone. The addition of ADT to RT produced a notable local and systemic effect, regardless of ST- or LT-ADT. The LF rate decreased from 34% with RT alone to 21% with ST-ADT and further to 15% with LT-ADT. The DM and DSM rates also showed a similar trend among RT alone, RT+ST-ADT, and RT+LT-ADT. The combination of RT+LT-ADT resulted in the best long-term clinical outcomes, indicating that both RT and ADT are important parts of multimodal therapy

  13. Increase in visceral and subcutaneous abdominal fat in men with prostate cancer treated with androgen deprivation therapy.

    Science.gov (United States)

    Hamilton, E J; Gianatti, E; Strauss, B J; Wentworth, J; Lim-Joon, D; Bolton, D; Zajac, J D; Grossmann, M

    2011-03-01

    Androgen deprivation therapy (ADT) for prostate cancer is associated with increases in fat mass and risk of type 2 diabetes; however, the relationship between sex steroid deficiency and abdominal fat distribution remains controversial. We conducted a 12-month prospective observational study at a tertiary referral centre. We investigated changes in abdominal fat distribution and insulin resistance in 26 men (70.6±6.8 years) with nonmetastatic prostate cancer during the first year of ADT. Twelve months of ADT increased visceral abdominal fat area by 22% (from 160.8±61.7 to 195.9±69.7 cm(2) ; Pfat area by 13% (from 240.7±107.5 to 271.3±92.8 cm(2) ; PFat mass increased by 14% (+3.4 kg; Ptestosterone (TT) was inversely associated with visceral fat area independent of oestradiol (E2), but E2 was not associated with visceral fat area independent of TT. Visceral fat area, not TT or E2, was independently associated with insulin resistance. ADT for prostate cancer results in accumulation of both visceral and subcutaneous abdominal fat. Increased visceral fat area appears more closely linked to testosterone than oestradiol deficiency. Increased insulin resistance may arise secondary to visceral fat accumulation, rather than as a direct result of sex steroid deficiency. © 2011 Blackwell Publishing Ltd.

  14. Expanded risk groups help determine which prostate radiotherapy sub-group may benefit from adjuvant androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Williams Scott G

    2008-04-01

    Full Text Available Abstract Purpose To assess whether an expanded (five level risk stratification system can be used to identify the sub-group of intermediate risk patients with prostate cancer who benefit from combining androgen deprivation therapy (ADT with external beam radiotherapy (EBRT. Materials and methods Using a previously validated 5-risk group schema, a prospective non-randomized data set of 1423 men treated at the British Columbia Cancer Agency was assessed for the primary end point of biochemical control (bNED with the RTOG-ASTRO "Phoenix" definition (lowest PSA to date + 2 ng/mL, both with and without adjuvant ADT. The median follow-up was 5 years. Results There was no bNED benefit for ADT in the low or low intermediate groups but there was a statistically significant bNED benefit in the high intermediate, high and extreme risk groups. The 5-year bNED rates with and without ADT were 70% and 73% respectively for the low intermediate group (p = non-significant and 72% and 58% respectively for the high intermediate group (p = 0.002. Conclusion There appears to be no advantage to ADT where the Gleason score is 6 or less and PSA is 15 or less. ADT is beneficial in patients treated to standard dose radiation with Gleason 6 disease and a PSA greater than 15 or where the Gleason score is 7 or higher.

  15. [Histopathological changes due to transurethural microwave thermotherapy associated with androgen deprivation therapy in patients with localized prostate cancer].

    Science.gov (United States)

    Jujo, Yutaka; Koshiba, Ken; Suzuki, Ryuta; Hoshiai, Osamu; Endo, Tadao; Aihara, Masahiro; Katsuta, Masayuki; Nakajo, Hirotaka

    2006-03-01

    The 2nd generation transurethral microwave thermotherapy (TUMT), equipped with high energy microwave generator and urethral cooling device is widely accepted as an less invasive effective modality to treat benign prostatic hyperplasia. For prostatic cancer, however, it is generally estimated as insufficient because of limitation in penetration of microwave into deep prostatic tissue. In this study, we examined histopathologic changes after androgen deprivation theraphy (ADT) and TUMT. Ten patients with localized prostate cancer underwent ADT for 3 months, and then TUMT was proceeded using Urowave (Dornier MedTech GmbH). Additional 3 months after TUMT and continued ADT, TURP in radical fashion was performed in all the patients, and all the resected chips were submitted for pathological study. Significant reduction in prostate volume was noted after NHT for 3 months from 37.4 +/- 9.6 ml to 22.0 +/- 5.6 ml. The pathological study of resected chips revealed progressive fibrotic changes without viable cancer cells in 9 of 10 patients. In 1 patient, however, some remnant of carcinomatous foci were noted in a resected chip from the middle lobe of the prostate. Although the number of patient is limited and longer follow-up is needed, the results in present series was interested and worth considering.

  16. Multimodal therapy for locally advanced prostate cancer: the roles of radiotherapy, androgen deprivation therapy, and their combination

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sung Uk; Cho, Kwan Ho [The Proton Therapy Center, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)

    2017-09-15

    Locally advanced prostate cancer (LAPC) is defined as histologically proven T3–4 prostatic adenocarcinoma. In this review, we define the individual roles of radiotherapy (RT), short-term (ST-) and long-term (LT-) androgen deprivation therapy (ADT), and their combination in multimodal therapy for LAPC. Despite limitations in comparing the clinical outcomes among published papers, in the present study, a trend of 10-year clinical outcomes was roughly estimated by calculating the average rates weighted by the cohort number. With RT alone, the following rates were estimated: 87% biochemical failure, 34% local failure (LF), 48% distant metastasis (DM), 38% overall survival (OS), and 27% disease-specific mortality (DSM). Those associated with ADT alone were 74% BCF, 54% OS, and 25% DSM, which appeared to be better than those of RT alone. The addition of ADT to RT produced a notable local and systemic effect, regardless of ST- or LT-ADT. The LF rate decreased from 34% with RT alone to 21% with ST-ADT and further to 15% with LT-ADT. The DM and DSM rates also showed a similar trend among RT alone, RT+ST-ADT, and RT+LT-ADT. The combination of RT+LT-ADT resulted in the best long-term clinical outcomes, indicating that both RT and ADT are important parts of multimodal therapy.

  17. One night of partial sleep deprivation increased biomarkers of muscle and cardiac injuries during acute intermittent exercise.

    Science.gov (United States)

    Mejri, Mohamed A; Yousfi, Narimen; Hammouda, Omar; Tayech, Amel; Ben Rayana, Mohamed C; Driss, Tarak; Chaouachi, Anis; Souissi, Nizar

    2017-05-01

    The aim of this study was to evaluate the effect of two types of partial sleep deprivation (PSD) on biomarkers of muscle and cardiac injuries in response to acute intermittent exercise in professional athletes. In a counterbalanced order, ten healthy male Taekwondo athletes were asked to perform the Yo-Yo Intermittent Recovery Test (YYIRT) in three conditions, allowing a 36 h recovery period in between: 1) following a full night of habitual sleep known as a reference sleep night (RN); 2) following PSD in the beginning of the night (PSDBN); and 3) following PSD in the end of the night (PSDEN). Heart rate (HR) and arterial oxygen saturation (SaO2) were measured during exercise. Blood samples were taken just before and 3 min after the YYIRT to measure biomarkers related to muscle and cardiac injuries (BRMCI). No significant effect of PSD was observed for physiological parameters (i.e., HR and SaO2). However, a significant alteration of resting ultra-sensitive C-reactive protein (us-CRP) (Pexercise. Likewise, compared to RN, PSD affected creatine phosphokinase (CPK) and MYO levels in response to exercise (Pexercise, among Taekwondo athletes, in the evening of the following day. However, no rise of the physiological responses has been observed after the two types of PSD, at rest and in response to the exercise.

  18. Treatment of gynecomastia in patients with prostate cancer and androgen deprivation.

    Science.gov (United States)

    Bautista-Vidal, C; Barnoiu, O; García-Galisteo, E; Gómez-Lechuga, P; Baena-González, V

    2014-01-01

    Gynecomastia, defined as benign proliferation of glandular breast tissue has a prevalence of 32% to 72% in the male. In the urology setting, it is associated to patients with prostate cancer and hormone treatment with a prevalence of 15% in the case of complete hormone blockage and 75% in monotherapy. The different options of treatment in prostate cancer have changed in recent decades. Thus, we have focused on this subject to evaluate the different therapy options of hormone manipulation induced gynecomastia in prostate cancer patients. To synthesize the available evidence on the different therapeutic options in prostate cancer patients who develop gynecomastia due to the use of nonsteroidal antiandrogens and to generate a diagnostic algorithm and treatment. Using the PICO type structured search strategy (Patient or problem, Intervention, Comparison, Outcome or result) in the data bases of PubMed-Medline and Cochrane, identification was made of the relevant studies related to the treatment of gynecomastia in Prostate Cancer patients treated with nonsteroidal antiandrogens. We have found 3 possible therapeutic options for the treatment of gynecomastia and mastodynia in patients with hormone deprivation therapy for prostate cancer. The 10Gy radiotherapy would be an option for the treatment of gynecomastia, although not all the patients need prophylactic treatment since only 50% report moderate-severe discomfort. Another option is the use of drugs such as tamoxifen 20mg/day that lead to a significant decrease in the mammary effects. Gynecomastia and mastodynia, given their high incidence, make the physical examination a fundamental tool for all patients before initiating treatment with antiandrogens. The use of tamoxifen 20mg/day is the best treatment and prevention option against gynecomastia and mastodynia, while in the case of long-course established gynecomastia, surgery is the gold standard. Copyright © 2012 AEU. Published by Elsevier Espana. All rights reserved.

  19. Clinical (non-histological) diagnosis of advanced prostate cancer: Evaluation of treatment outcome after androgen deprivation therapy.

    Science.gov (United States)

    Heyns, Chris F; Basson, Jacque; Van der Merwe, Andre; Zarrabi, Amir D

    2014-08-08

    Introduction. Transrectal biopsy in suspected adenocarcinoma of the prostate (ACP) may cause significant morbidity and even mortality. A strong association between serum prostate-specific antigen (PSA) and tumour burden exists. If biopsy can be avoided in advanced disease, much morbidity and cost may be saved.Objective. To evaluate the reliability of using PSA and clinical features to establish a non-histological diagnosis of ACP.Methods. Androgen deprivation therapy (ADT) was used in 825 (56.2%) of 1 467 men with ACP. The diagnosis of ACP was made histologically in 607 patients (73.6%) and clinically alone in 218 (26.4%), based on a serum PSA level of >60 ng/ml, and/or clinical evidence of a T3 - T4 tumour on digital rectal examination, and/or imaging evidence of metastases. We compared two randomly selected groups treated with bilateral orchidectomy (BO) based on a clinical-only (n=90) v. histological (n=96) diagnosis of ACP.Results. There was no significant difference between the groups with regard to mean follow-up (26.1 v. 26.8 months), documented PSA relapse (70% v. 67.7%), and patients alive at last follow-up (91.1% v. 95.8%). ZAR1 068 200 (US$1 = ZAR8) was saved by treating men with advanced ACP on the basis of a clinical (non-histological) diagnosis only, and a total of ZAR24 321 000 was saved by using BO instead of luteinising hormone-releasing hormone agonists as ADT.Conclusion. A reliable clinical (non-histological) diagnosis of advanced ACP can be made based on serum PSA and clinical features. This avoids the discomfort and potentially serious complications of biopsy and saves cost.

  20. Clamp ablation of the testes compared to bilateral orchiectomy as androgen deprivation therapy for advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    AD Zarrabi

    2011-06-01

    Full Text Available PURPOSE: Burdizzo clamp ablation of the testes (CAT may provide an incisionless, cost-effective form of androgen deprivation therapy (ADT in men with adenocarcinoma of the prostate (ACP who find bilateral orchiectomy (BO unacceptable or can not afford medical ADT. The aim of this study was to compare CAT with BO as primary ADT in men with ACP. MATERIALS AND METHODS: Written, informed consent was obtained from men with locally advanced or metastatic ACP. Patients were prospectively randomized to BO (n = 9 or CAT (n = 10 under local anaesthesia, and were evaluated 3 and 7 days, 6 weeks and 3 months post-procedure. The protocol was approved by the local institutional ethics committee. Statistical analysis was performed using Student's, Mann-Whitney's and Fisher's tests. RESULTS: Mean duration of the procedure was significantly longer for BO than CAT (16.9 vs. 10.9 minutes. Mean pain scores during and after the procedure did not differ significantly. Serum testosterone decreased significantly on days 3 and 7 after CAT, but increased at 6 weeks, and was significantly higher than after BO. Serum luteinizing hormone increased significantly from day 3 after BO and from day 7 after CAT. Serum prostate specific antigen decreased significantly after BO, but not after CAT. Minor complications were more common after BO (89% than CAT (40%. In the 9 men who did not achieve castrate levels of testosterone after CAT, BO was performed. CONCLUSIONS: CAT was quicker to perform and had a lower complication rate, but was not as effective as BO in achieving castrate serum testosterone levels.

  1. Avoidance of androgen deprivation therapy in radiorecurrent prostate cancer as a clinically meaningful endpoint for salvage cryoablation.

    Science.gov (United States)

    Ginsburg, Kevin B; Elshafei, Ahmed; Yu, Changhong; Jones, J Stephen; Cher, Michael L

    2017-10-01

    To investigate the ability of salvage cryoablation of the prostate (SCAP) to delay the need for androgen deprivation therapy (ADT) in local recurrence after radiation therapy to the prostate using the Cryo-On-Line Database (COLD) registry. The COLD registry is comprised of a combination of retrospectively and prospectively collected data on patients undergoing primary and SCAP. Patients with local recurrence after radiation therapy were identified. Kaplan-Meier analysis was used to calculate ADT-free survival. We identified 898 patients that have undergone SCAP in the COLD registry. Overall, the calculated 5-year ADT-free survival probability was 0.713. When stratified by D'Amico risk group, 264 high-risk patients (71.9%), 234 intermediate-risk (86.7%),and 228 low-risk (87.7%) were free of ADT post-SCAP. This correlates with a 5-year ADT-free survival of 60.7, 73.9, and 82.4%, respectively. Patients with post-SCAP PSA nadir of <0.2 ng/mL had a 5 year ADT-free survival of 87.1% compared to 48.7% with a PSA nadir ≥0.2 ng/mL. Pre-operative ADT use or full versus partial gland SCAP did not have an effect on ADT use post-operatively. In 118 (55.4%) of patients with post-operative biochemical recurrence, ADT was not used. For patients with local recurrence after radiation, SCAP is an option that provides a high chance of avoiding or delaying ADT. The potential to delay ADT and its associated side effects should be a part of counseling sessions with the patient when discussing treatment options for locally recurrent prostate cancer after radiation. Avoidance of ADT is more clinically relevant than PSA elevation. © 2017 Wiley Periodicals, Inc.

  2. Course and Predictors of Cognitive Function in Patients With Prostate Cancer Receiving Androgen-Deprivation Therapy: A Controlled Comparison

    Science.gov (United States)

    Gonzalez, Brian D.; Jim, Heather S.L.; Booth-Jones, Margaret; Small, Brent J.; Sutton, Steven K.; Lin, Hui-Yi; Park, Jong Y.; Spiess, Philippe E.; Fishman, Mayer N.; Jacobsen, Paul B.

    2015-01-01

    Purpose Men receiving androgen-deprivation therapy (ADT) for prostate cancer may be at risk for cognitive impairment; however, evidence is mixed in the existing literature. Our study examined the impact of ADT on impaired cognitive performance and explored potential demographic and genetic predictors of impaired performance. Patients and Methods Patients with prostate cancer were assessed before or within 21 days of starting ADT (n = 58) and 6 and 12 months later. Age- and education-matched patients with prostate cancer treated with prostatectomy only (n = 84) and men without prostate cancer (n = 88) were assessed at similar intervals. Participants provided baseline blood samples for genotyping. Mean-level cognitive performance was compared using mixed models; cognitive impairment was compared using generalized estimating equations. Results ADT recipients demonstrated higher rates of impaired cognitive performance over time relative to all controls (P = .01). Groups did not differ at baseline (P > .05); however, ADT recipients were more likely to demonstrate impaired performance within 6 and 12 months (P for both comparisons < .05). Baseline age, cognitive reserve, depressive symptoms, fatigue, and hot flash interference did not moderate the impact of ADT on impaired cognitive performance (P for all comparisons ≥ .09). In exploratory genetic analyses, GNB3 single-nucleotide polymorphism rs1047776 was associated with increased rates of impaired performance over time in the ADT group (P < .001). Conclusion Men treated with ADT were more likely to demonstrate impaired cognitive performance within 6 months after starting ADT relative to matched controls and to continue to do so within 12 months after starting ADT. If confirmed, findings may have implications for patient education regarding the risks and benefits of ADT. PMID:25964245

  3. Three linked nomograms for predicting biochemical failure in prostate cancer treated with radiotherapy plus androgen deprivation therapy

    International Nuclear Information System (INIS)

    Lopez-Torrecilla, Jose; Boladeras, Anna; Angeles Cabeza, Maria; Zapatero, Almudena; Jove, Josep; Esteban, Luis M.; Henriquez, Ivan; Casana, Manuel; Mengual, Jose Luis; Gonzalez-San Segundo, Carmen; Gomez-Caamano, Antonio; Hervas, Asuncion; Munoz, Julia Luisa; Sanz, Gerardo

    2015-01-01

    Nomograms were established to predict biochemical recurrence (BCR) after radiotherapy (RT) with a low weight of the characteristic variables of RT and androgen deprivation therapy (ADT). Our aim is to provide a new stratified tool for predicting BCR at 4 and 7 years in patients treated using RT with radical intent. A retrospective, nonrandomized analysis was performed on 5044 prostate cancer (PCa) patients with median age 70 years, who received RT - with or without ADT - between November 1992 and May 2007. Median follow-up was 5.5 years. BCR was defined as a rise in serum prostate-specific antigen (PSA) of 2 ng/ml over the post-treatment PSA nadir. Univariate association between predictor variables and BCR was assessed by the log-rank test, and three linked nomograms were created for multivariate prognosis of BCR-free survival. Each nomogram corresponds to a category of the Gleason score - either 6,7, or 8-10 - and all of them were created from a single proportional hazards regression model stratified also by months of ADT (0, 1-6, 7-12, 13-24, 25-36, 36-60). The performance of this model was analyzed by calibration, discrimination, and clinical utility. Initial PSA, clinical stage, and RT dose were significant variables (p < 0.01). The model showed a good calibration. The concordance probability was 0.779, improving those obtained with other nomograms (0.587, 0.571, 0.554) in the database. Survival curves showed best clinical utility in a comparison with National Comprehensive Cancer Network (NCCN) risk groups. For each Gleason score category, the nomogram provides information on the benefit of adding ADT to a specific RT dose. (orig.) [de

  4. Does primary androgen-deprivation therapy delay the receipt of secondary cancer therapy for localized prostate cancer?

    Science.gov (United States)

    Lu-Yao, Grace L; Albertsen, Peter C; Li, Hui; Moore, Dirk F; Shih, Weichung; Lin, Yong; DiPaola, Robert S; Yao, Siu-Long

    2012-12-01

    Despite evidence that shows no survival advantage, many older patients receive primary androgen-deprivation therapy (PADT) shortly after the diagnosis of localized prostate cancer (PCa). This study evaluates whether the early use of PADT affects the subsequent receipt of additional palliative cancer treatments such as chemotherapy, palliative radiation therapy, or intervention for spinal cord compression or bladder outlet obstruction. This longitudinal population-based cohort study consists of Medicare patients aged ≥ 66 yr diagnosed with localized PCa from 1992 to 2006 in areas covered by the Surveillance Epidemiology and End Results (SEER) program. SEER-Medicare linked data through 2009 were used to identify the use of PADT and palliative cancer therapy. Instrumental variable analysis methods were used to minimize confounding effects. Confidence intervals were derived from the bootstrap estimates. This study includes 29 775 men who did not receive local therapy for T1-T2 PCa within the first year of cancer diagnosis. Among low-risk patients (Gleason score 2-7 in 1992-2002 and Gleason score 2-6 in 2003-2006) with a median age of 78 yr and a median follow-up of 10.3 yr, PADT was associated with a 25% higher use of chemotherapy (hazard ratio [HR]: 1.25; 95% confidence interval [CI], 1.08-1.44) and a borderline higher use of any palliative cancer treatment (HR: 1.07; 95% CI, 0.97-1.19) within 10 yr of diagnosis in regions with high PADT use compared with regions with low PADT use. Because this study was limited to men >65 yr, the results may not be applicable to younger patients. Early treatment of low-risk, localized PCa with PADT does not delay the receipt of subsequent palliative therapies and is associated with an increased use of chemotherapy. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  5. Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-Term Update of NRG Oncology RTOG 9202

    Energy Technology Data Exchange (ETDEWEB)

    Lawton, Colleen A.F., E-mail: clawton@mcw.edu [Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Lin, Xiaolei [University of Chicago, Chicago, Illinois (United States); Hanks, Gerald E. [Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Lepor, Herbert [New York University, New York, New York (United States); Grignon, David J. [Indiana University, Indianapolis, Indiana (United States); Brereton, Harmar D. [Northeast Radiation Oncology Center, Dunmore, Pennsylvania (United States); Bedi, Meena [Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Rosenthal, Seth A. [Sutter General Hospital, Sacramento, California (United States); Zeitzer, Kenneth L. [Albert Einstein Medical Center, Philadelphia, Pennsylvania (United States); Venkatesan, Varagur M. [London Regional Cancer Program, London, Ontario (Canada); Horwitz, Eric M. [Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Pisansky, Thomas M. [Mayo Clinic, Rochester, Minnesota (United States); Kim, Harold [Wayne State University-Karmanos Cancer Institute, Detroit, Michigan (United States); Parliament, Matthew B. [Cross Cancer Institute, Edmonton, Alberta (Canada); Rabinovitch, Rachel [University of Colorado Denver, Denver, Colorado (United States); Roach, Mack [University of California, San Francisco, California (United States); Kwok, Young [University of Maryland Medical System, Baltimore, Maryland (United States); Dignam, James J. [University of Chicago, Chicago, Illinois (United States); NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Sandler, Howard M. [Cedars-Sinai Medical Center, Los Angeles, California (United States)

    2017-06-01

    Purpose: Trial RTOG 9202 was a phase 3 randomized trial designed to determine the optimal duration of androgen deprivation therapy (ADT) when combined with definitive radiation therapy (RT) in the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate. Long-term follow-up results of this study now available are relevant to the management of this disease. Methods and Materials: Men (N=1554) with adenocarcinoma of the prostate (cT2c-T4, N0-Nx) with a prostate-specific antigen (PSA) <150 ng/mL and no evidence of distant metastasis were randomized (June 1992 to April 1995) to short-term ADT (STAD: 4 months of flutamide 250 mg 3 times per day and goserelin 3.6 mg per month) and definitive RT versus long-term ADT (LTAD: STAD with definitive RT plus an additional 24 months of monthly goserelin). Results: Among 1520 protocol-eligible and evaluable patients, the median follow-up time for this analysis was 19.6 years. In analysis adjusted for prognostic covariates, LTAD improved disease-free survival (29% relative reduction in failure rate, P<.0001), local progression (46% relative reduction, P=.02), distant metastases (36% relative reduction, P<.0001), disease-specific survival (30% relative reduction, P=.003), and overall survival (12% relative reduction, P=.03). Other-cause mortality (non–prostate cancer) did not differ (5% relative reduction, P=.48). Conclusions: LTAD and RT is superior to STAD and RT for the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate and should be considered the standard of care.

  6. Recognizing False Biochemical Failure Calls After Radiation With or Without Neo-Adjuvant Androgen Deprivation for Prostate Cancer

    International Nuclear Information System (INIS)

    Denham, James W.; Kumar, Mahesh; Gleeson, Paul S.; Lamb, David S.; Joseph, David FRANZCR.; Atkinson, Chris FRANZCR.; Matthews, John FRANZCR.; Tai, K.-H.; Spry, Nigel A.; Christie, David; Turner, Sandra FRANZCR.; Greer, Peter B.; D'Este, Catherine; Steigler, Allison

    2009-01-01

    Purpose: We studied prostate-specific antigen (PSA) changes after radiation with or without neoadjuvant androgen deprivation to determine posttreatment PSA scenarios in which false-positive biochemical failures (FPBF) are most likely to occur. Methods and Materials: In the Trans-Tasman Radiation Oncology 96.01 Group trial, patients with T2b, 2c, 3, 4 N0 prostate cancer were randomized to 3 or 6 months goserelin and flutamide (STAD) before and during 66 Gy to the prostate and seminal vesicles (XRT) or to XRT alone. Piecewise longitudinal changes in PSA before relapse were characterized and quantified to determine which might cause FPBF calls. Results: Between 1996 and 2000, 802 eligible patients were randomized. Of these, 492 met the criteria for American Society for Therapeutic Radiology and Oncology (ASTRO) failure and 467 for Phoenix failure. Seventy-seven ASTRO fails and 39 Phoenix fails were deemed false positives (FPs). The majority of FPBFs were associated with the 'plateauing' in PSA values that follow posttreatment nadir. FPBFs were particularly common in men treated with STAD, in whom small, consecutive PSA rises before or during this phenomenon triggered 56 FP ASTRO fail calls. In these men, the Phoenix fail criteria triggered only 15 FPBF calls. However, the Phoenix criteria were more vulnerable than ASTRO to short-term isolated PSA rises during plateau, which resulted in 15 Phoenix fail calls but only 3 FP ASTRO fails. Conclusions: The Phoenix definition avoided 50% of FPBF calls that occurred with the ASTRO definition. Failures should be confirmed by further PSA rises before investigation and treatment is considered.

  7. Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-Term Update of NRG Oncology RTOG 9202

    International Nuclear Information System (INIS)

    Lawton, Colleen A.F.; Lin, Xiaolei; Hanks, Gerald E.; Lepor, Herbert; Grignon, David J.; Brereton, Harmar D.; Bedi, Meena; Rosenthal, Seth A.; Zeitzer, Kenneth L.; Venkatesan, Varagur M.; Horwitz, Eric M.; Pisansky, Thomas M.; Kim, Harold; Parliament, Matthew B.; Rabinovitch, Rachel; Roach, Mack; Kwok, Young; Dignam, James J.; Sandler, Howard M.

    2017-01-01

    Purpose: Trial RTOG 9202 was a phase 3 randomized trial designed to determine the optimal duration of androgen deprivation therapy (ADT) when combined with definitive radiation therapy (RT) in the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate. Long-term follow-up results of this study now available are relevant to the management of this disease. Methods and Materials: Men (N=1554) with adenocarcinoma of the prostate (cT2c-T4, N0-Nx) with a prostate-specific antigen (PSA) <150 ng/mL and no evidence of distant metastasis were randomized (June 1992 to April 1995) to short-term ADT (STAD: 4 months of flutamide 250 mg 3 times per day and goserelin 3.6 mg per month) and definitive RT versus long-term ADT (LTAD: STAD with definitive RT plus an additional 24 months of monthly goserelin). Results: Among 1520 protocol-eligible and evaluable patients, the median follow-up time for this analysis was 19.6 years. In analysis adjusted for prognostic covariates, LTAD improved disease-free survival (29% relative reduction in failure rate, P<.0001), local progression (46% relative reduction, P=.02), distant metastases (36% relative reduction, P<.0001), disease-specific survival (30% relative reduction, P=.003), and overall survival (12% relative reduction, P=.03). Other-cause mortality (non–prostate cancer) did not differ (5% relative reduction, P=.48). Conclusions: LTAD and RT is superior to STAD and RT for the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate and should be considered the standard of care.

  8. Efficacy of walking exercise in promoting cognitive-psychosocial functions in men with prostate cancer receiving androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Lee C

    2012-07-01

    Full Text Available Abstract Background Prostate cancer is the most commonly diagnosed non-melanoma cancer among men. Androgen deprivation therapy (ADT has been the core therapy for men with advanced prostate cancer. It is only in recent years that clinicians began to recognize the cognitive-psychosocial side effects from ADT, which significantly compromise the quality of life of prostate cancer survivors. The objectives of the study are to determine the efficacy of a simple and accessible home-based, walking exercise program in promoting cognitive and psychosocial functions of men with prostate cancer receiving ADT. Methods A 6-month prospective, single-blinded, randomized controlled trial will be conducted to compare the Exercise Group with the Control Group. Twenty men with prostate cancer starting ADT will be recruited and randomly assigned to one of the two groups: the Exercise Group will receive instructions in setting up an individualized 6-month home-based, walking exercise program, while the Control Group will receive standard medical advice from the attending physician. The primary outcomes will be psychosocial and cognitive functions. Cognitive functions including memory, attention, working memory, and executive function will be assessed using a battery of neurocognitive tests at baseline and 6 months. Psychosocial functions including depression, anxiety and self-esteem will be assessed at baseline, 3 and 6 months using the Center for Epidemiological Studies Depression Scale, Spielberger State-Trait Anxiety Inventory, and Rosenberg Self-Esteem Scale. Discussion The significance of the cognitive-psychosocial side effects of ADT in men with prostate cancer has only been recently recognized, and the management remains unclear. This study addresses this issue by designing a simple and accessible home-based, exercise program that may potentially have significant impact on reducing the cognitive and psychosocial side effects of ADT, and ultimately

  9. Radical Prostatectomy Versus Radiation and Androgen Deprivation Therapy for Clinically Localized Prostate Cancer: How Good Is the Evidence?

    Energy Technology Data Exchange (ETDEWEB)

    Roach, Mack, E-mail: mroach@radonc.ucsf.edu [Department of Radiation Oncology, University of California San Francisco, San Francisco, California (United States); Ceron Lizarraga, Tania L. [Department of Radiation Oncology, University of California San Francisco, San Francisco, California (United States); Lazar, Ann A. [Department of Radiation Oncology, University of California San Francisco, San Francisco, California (United States); Division of Oral Epidemiology and Dental Public Health, Division of Biostatistics, University of California San Francisco, San Francisco, California (United States)

    2015-12-01

    Purpose: The optimal treatment of clinically localized prostate cancer is controversial. Most studies focus on biochemical (PSA) failure when comparing radical prostatectomy (RP) with radiation therapy (RT), but this endpoint has not been validated as predictive of overall survival (OS) or cause-specific survival (CSS). We analyzed the available literature to determine whether reliable conclusions could be made concerning the effectiveness of RP compared with RT with or without androgen deprivation therapy (ADT), assuming current treatment standards. Methods: Articles published between February 29, 2004, and March 1, 2015, that compared OS and CSS after RP or RT with or without ADT were included. Because the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system emphasis is on randomized controlled clinical trials, a reliability score (RS) was explored to further understand the issues associated with the study quality of observational studies, including appropriateness of treatment, source of data, clinical characteristics, and comorbidity. Lower RS values indicated lower reliability. Results: Fourteen studies were identified, and 13 were completely evaluable. Thirteen of the 14 studies (93%) were observational studies with low-quality evidence. The median RS was 12 (range, 5-18); the median difference in 10-year OS and CSS favored RP over RT: 10% and 4%, respectively. In studies with a RS ≤12 (average RS 9) the 10-year OS and CSS median differences were 17% and 6%, respectively. For studies with a RS >12 (average RS 15.5), the 10-year OS and CSS median differences were 5.5% and 1%, respectively. Thus, we observed an association between low RS and a higher percentage difference in OS and CSS. Conclusions: Reliable evidence that RP provides a superior CSS to RT with ADT is lacking. The most reliable studies suggest that the differences in 10-year CSS between RP and RT are small, possibly <1%.

  10. Strength training induces muscle hypertrophy and functional gains in black prostate cancer patients despite androgen deprivation therapy.

    Science.gov (United States)

    Hanson, Erik D; Sheaff, Andrew K; Sood, Suchi; Ma, Lei; Francis, Jack D; Goldberg, Andrew P; Hurley, Ben F

    2013-04-01

    Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with weakness, fatigue, sarcopenia, and reduced quality of life (QoL). Black men have a higher incidence and mortality from PCa than Caucasians. We hypothesized that despite ADT, strength training (ST) would increase muscle power and size, thereby improving body composition, physical function, fatigue levels, and QoL in older black men with PCa. Muscle mass, power, strength, endurance, physical function, fatigue perception, and QoL were measured in 17 black men with PCa on ADT before and after 12 weeks of ST. Within-group differences were determined using t tests and regression models. ST significantly increased total body muscle mass (2.7%), thigh muscle volume (6.4%), power (17%), and strength (28%). There were significant increases in functional performance (20%), muscle endurance (110%), and QoL scores (7%) and decreases in fatigue perception (38%). Improved muscle function was associated with higher functional performance (R (2) = 0.54) and lower fatigue perception (R (2) = 0.37), and both were associated with improved QoL (R (2) = 0.45), whereas fatigue perception tended to be associated with muscle endurance (R (2) = 0.37). ST elicits muscle hypertrophy even in the absence of testosterone and is effective in counteracting the adverse functional consequences of ADT in older black men with PCa. These improvements are associated with reduced fatigue perception, enhanced physical performance, and improved QoL. Thus, ST may be a safe and well-tolerated therapy to prevent the loss of muscle mass, strength, and power commonly observed during ADT.

  11. A quality assurance audit: phase iii trial of maximal androgen deprivation in prostate cancer (TROG 96.01)

    International Nuclear Information System (INIS)

    Steigler, A.; Kovacev, O.; Denham, J.; Lamb, D.; North, J.

    2000-01-01

    In 1997 the Trans-Tasman Radiation Oncology Group (TROG) performed a quality assurance (QA) audit of its phase III randomized clinical trial investigating the effectiveness of different durations of maximal androgen deprivation prior to and during definitive radiation therapy for locally advanced carcinoma of the prostate (TROG 96.01). The audit reviewed a total of 60 cases from 15 centres across Australia and New Zealand. In addition to verification of technical adherence to the protocol, the audit also incorporated a survey of centre planning techniques and a QA time/cost analysis. The present report builds on TROG's first technical audit conducted in 1996 for the phase III accelerated head and neck trial (TROG 91.01) and highlights the significant progress TROG has made in the interim period. The audit provides a strong validation of the results of the 96.01 trial, as well as valuable budgeting and treatment planning information for future trials. Overall improvements were detected in data quality and quantity, and in protocol compliance, with a reduction in the rate of unacceptable protocol violations from 10 to 4%. Audit design, staff education and increased data management resources were identified as the main contributing factors to these improvements. In addition, a budget estimate of $100 per patient has been proposed for conducting similar technical audits. The next major QA project to be undertaken by TROG during the period 1998-1999 is an intercentre dosimetry study. Trial funding and staff education have been targeted as the key major issues essential to the continued success and expansion of TROG's QA programme. Copyright (1999) Blackwell Science Pty Ltd

  12. Patterns of androgen deprivation therapies among men diagnosed with localised prostate cancer: a population-based study.

    Science.gov (United States)

    Lycken, Magdalena; Garmo, Hans; Adolfsson, Jan; Stattin, Pär; Holmberg, Lars; Bill-Axelson, Anna

    2014-07-01

    Many men diagnosed with localised prostate cancer will eventually be treated with androgen deprivation therapy (ADT). ADT is associated with adverse effects and its timing is controversial. Data on patterns of use are scarce. We describe patterns of ADT use, defined as castration (medical and surgical) or antiandrogen monotherapy initiated after primary treatment, in a population-based cohort. Data were extracted from the population-based Prostate Cancer data Base Sweden (PCBaSe). Totally 45,147 men diagnosed between 1997 and 2009 with clinical stage T1-2, N0-NX, M0-MX and prostate specific antigen (PSA)<50ng/ml without primary ADT were included. Outcomes in the period 2006 through 2010 were analysed using a period analysis approach. The cumulative incidence of castration at 10years after diagnosis was 11.6% (95% confidence interval (CI), 11.0-12.2%). The corresponding proportion of antiandrogen monotherapy was 10.8% (95% CI, 10.2-11.4%). Castration was the dominant therapy among men on deferred treatment. The probability of receiving castration rather than antiandrogen monotherapy increased with age. Estimated median durations of castration ranged from 4years in the deferred treatment high-risk group to 17years in the prostatectomy low-risk group. The main limitation was the lack of information on progression to metastatic disease and PSA at the time for initiation of ADT. When initiated early after curative treatment, the duration of castration can be decades. The findings indicate that more accurate tools are necessary to guide which men should be selected for ADT as secondary treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Factors associated with the omission of androgen deprivation therapy in radiation-managed high-risk prostate cancer.

    Science.gov (United States)

    Chen, Yu-Wei; Muralidhar, Vinayak; Mahal, Brandon A; Nezolosky, Michelle D; Beard, Clair J; Choueiri, Toni K; Hoffman, Karen E; Martin, Neil E; Orio, Peter F; Sweeney, Christopher J; Feng, Felix Y; Trinh, Quoc-Dien; Nguyen, Paul L

    Androgen deprivation therapy (ADT) has been shown to improve survival for men with unfavorable-risk prostate cancer (PCa). We investigated the utilization and factors associated with the omission of ADT in radiation-managed high-risk PCa. We used the National Cancer Database to identify men with National Comprehensive Cancer Network high-risk PCa treated with external beam radiation therapy (EBRT) with or without brachytherapy boost from 2004 to 2012. Multivariable logistic regression adjusting for clinical and sociodemographic factors was used to identify independent predictors for ADT use. A total of 57,968 radiation-treated high-risk PCa men were included in our analysis. There were 49,363 patients (85.2%) treated with EBRT alone and 8605 patients (14.8%) treated with EBRT plus brachytherapy boost. Overall, 77% of men received ADT. In multivariable regression analysis, the use of brachytherapy boost was associated with a significantly lower utilization of ADT (70% vs. 78%; adjusted odds ratio [AOR]: 0.65; 95% CI: 0.62-0.69; p-Value use was seen with higher Gleason scores, PSA, and T-category (all p-Values <0.001). Approximately one in four men with radiation-managed high-risk PCa do not receive ADT, which may reflect concerns about its toxicity profile despite known improvements in overall survival. Practice patterns suggest that some providers believe dose escalation through brachytherapy boost may obviate the need for ADT in some high-risk patients, but this hypothesis requires further testing. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  14. Prevalent and incident use of androgen deprivation therapy among men with prostate cancer in the United States.

    Science.gov (United States)

    Gilbert, Scott M; Kuo, Yong-Fang; Shahinian, Vahakn B

    2011-01-01

    Androgen deprivation therapy (ADT) for prostate cancer increased substantially through the 1990s, but more recent national trends regarding incident and prevalent use have been incompletely characterized. Linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data were used to study patterns of ADT utilization. Prevalence of ADT in the male Medicare population was estimated by examining a cohort of prostate cancer patients and a 5% noncancer control population, from 1991 to 2005. ADT use across different indications was examined for men with incident cancers from 2000 to 2002. Nested logit models were used to examine determinants of ADT use in men with lower risk prostate cancer not treated definitively by surgery or radiation. Prevalent ADT use increased through the 1990s, peaked in 2000 at 3.17% of all male Medicare beneficiaries, subsequently stabilized, then dropped in 2005 to 2.92%. Between 2000 and 2002, use in incident prostate cancer was stable, with 44.8% use in all cases, 15% of cases as an adjuvant with radiation, and 14% as a primary therapy. In the nested logit model, predictors of ADT use in a lower risk setting were older age, higher stage and grade, and elevated prostate-specific antigen levels. Following a period of rapid expansion during the 1990s, incident and prevalent use of ADT has leveled, and may be starting to decline. Further research is needed to monitor how reductions in reimbursement for GnRH agonists will affect appropriate use of ADT as well as use in settings where its benefits may be marginal. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Sleep disturbance in men receiving androgen deprivation therapy for prostate cancer: The role of hot flashes and nocturia.

    Science.gov (United States)

    Gonzalez, Brian D; Small, Brent J; Cases, Mallory G; Williams, Noelle L; Fishman, Mayer N; Jacobsen, Paul B; Jim, Heather S L

    2018-02-01

    Patients with prostate cancer receiving androgen deprivation therapy (ADT) are at risk of sleep disturbance; however, to the authors' knowledge, the mechanisms by which ADT may affect sleep are not well understood. The current study compared objective and subjective sleep disturbance in ADT recipients and controls and examined whether sleep disturbance in ADT recipients is attributable to the influence of ADT on hot flashes and nocturia. Patients with prostate cancer were assessed before or within 1 month after the initiation of ADT as well as 6 months and 12 months later (78 patients). Patients with prostate cancer were treated with prostatectomy only (99 patients) and men with no history of cancer (108 men) were assessed at similar intervals. Participants self-reported their sleep disturbance (Insomnia Severity Index) and interference from hot flashes (Hot Flash Related Daily Interference Scale). One hundred participants also wore actigraphs for 3 days at the 6-month assessment to measure objective sleep disturbance and reported their nocturia frequency. ADT recipients reported worse sleep disturbance, higher rates of clinically significant sleep disturbance, and greater hot flash interference than controls (Ps≤.03). In cross-sectional analyses among those with actigraphy data, ADT recipients had greater objective sleep disturbance and more episodes of nocturia (Pssleep disturbance was partly attributable to nocturia and hot flashes (Pssleep may be partly explained by nocturia and hot flash interference. Future studies should examine behavioral and pharmacologic interventions to address these symptoms among ADT recipients. Cancer 2018;124:499-506. © 2017 American Cancer Society. © 2017 American Cancer Society.

  16. Sunitinib Plus Androgen Deprivation and Radiation Therapy for Patients With Localized High-Risk Prostate Cancer: Results From a Multi-institutional Phase 1 Study

    Energy Technology Data Exchange (ETDEWEB)

    Corn, Paul G., E-mail: pcorn@mdanderson.org [Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Song, Danny Y. [Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland (United States); Heath, Elisabeth; Maier, Jordan [Karmanos Cancer Institute, Wayne State University, Detroit, Michigan (United States); Meyn, Raymond [Department of Experimental Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Kuban, Deborah [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); DePetrillo, Thomas A. [Department of Radiation Oncology, Tufts Medical Center, Boston, Massachusetts (United States); Mathew, Paul, E-mail: pmathew@tuftsmedicalcenter.org [Department of Hematology-Oncology, Tufts Medical Center, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States)

    2013-07-01

    Purpose: To evaluate the feasibility of administering sunitinib in combination with androgen deprivation therapy and external-beam intensity modulated radiation therapy (XRT) in patients with localized high-risk prostate cancer. Methods and Materials: Seventeen men with localized adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or prostate-specific antigen >20 ng/mL received initial androgen deprivation (leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50 mg daily) for 4-8 weeks before oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks after XRT (75.6 Gy in 42 fractions to prostate and seminal vesicles). A 3+3 sequential dose-escalation design was used to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose of sunitinib. Results: Sunitinib at 12.5- and 25-mg dose levels was well tolerated. The first 4 patients enrolled at 37.5 mg experienced a DLT during lead-in, and a drug interaction between sunitinib and bicalutamide was suspected. The protocol was revised and concurrent bicalutamide omitted. Of the next 3 patients enrolled at 37.5 mg, 2 of 3 receiving concurrent therapy experienced DLTs during radiation: grade 3 diarrhea and grade 3 proctitis, respectively. Only 1 of 7 patients completed sunitinib at 37.5 mg daily, whereas 3 of 3 patients (25 mg as starting dose) and 3 of 4 patients (25 mg as reduced dose) completed therapy. Conclusions: The feasibility of combined vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR) inhibitor therapy, androgen deprivation, and radiation therapy for prostate cancer was established. Using a daily dosing regimen with lead-in, concurrent, and post-XRT therapy, the recommended phase 2 dose of sunitinib is 25 mg daily.

  17. Nutrition therapy with high intensity interval training to improve prostate cancer-related fatigue in men on androgen deprivation therapy: a study protocol.

    Science.gov (United States)

    Baguley, Brenton J; Skinner, Tina L; Leveritt, Michael D; Wright, Olivia R L

    2017-01-03

    Cancer-related fatigue is one of the most prevalent, prolonged and distressing side effects of prostate cancer treatment with androgen deprivation therapy. Preliminary evidence suggests natural therapies such as nutrition therapy and structured exercise prescription can reduce symptoms of cancer-related fatigue. Men appear to change their habitual dietary patterns after prostate cancer diagnosis, yet prostate-specific dietary guidelines provide limited support for managing adverse side effects of treatment. The exercise literature has shown high intensity interval training can improve various aspects of health that are typically impaired with androgen deprivation therapy; however exercise at this intensity is yet to be conducted in men with prostate cancer. The purpose of this study is to examine the effects of nutrition therapy beyond the current healthy eating guidelines with high intensity interval training for managing cancer-related fatigue in men with prostate cancer treated with androgen deprivation therapy. This is a two-arm randomized control trial of 116 men with prostate cancer and survivors treated with androgen deprivation therapy. Participants will be randomized to either the intervention group i.e. nutrition therapy and high intensity interval training, or usual care. The intervention group will receive 20 weeks of individualized nutrition therapy from an Accredited Practising Dietitian, and high intensity interval training (from weeks 12-20 of the intervention) from an Accredited Exercise Physiologist. The usual care group will maintain their standard treatment regimen over the 20 weeks. Both groups will undertake primary and secondary outcome testing at baseline, week 8, 12, and 20; testing includes questionnaires of fatigue and quality of life, objective measures of body composition, muscular strength, cardiorespiratory fitness, biomarkers for disease progression, as well as dietary analysis. The primary outcomes for this trial are measures of

  18. A Comparison Between Low-Dose-Rate Brachytherapy With or Without Androgen Deprivation, External Beam Radiation Therapy With or Without Androgen Deprivation, and Radical Prostatectomy With or Without Adjuvant or Salvage Radiation Therapy for High-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ciezki, Jay P., E-mail: ciezkij@ccf.org [Taussig Cancer Institute, Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio (United States); Weller, Michael; Reddy, Chandana A.; Kittel, Jeffrey; Singh, Harguneet; Tendulkar, Rahul; Stephans, Kevin L. [Taussig Cancer Institute, Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio (United States); Ulchaker, James; Angermeier, Kenneth; Stephenson, Andrew; Campbell, Steven; Haber, Georges-Pascal; Klein, Eric A. [Glickman Urological and Kidney Institute, Department of Urology, Cleveland Clinic, Cleveland, Ohio (United States)

    2017-04-01

    Purpose: We compare the efficacy and toxicity among the 3 major modalities available used to treat high-risk prostate cancer (HRCaP). Methods and Materials: From 1996 to 2012, 2557 HRCaP patients were treated: 734 received external beam radiation therapy (EBRT) with or without androgen deprivation therapy (ADT), 515 received low-dose-rate prostate brachytherapy (LDR) with or without ADT, and 1308 received radical prostatectomy (RP) with or without EBRT. Biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), and prostate cancer–specific mortality (PCSM) were assessed. Toxicity was assessed using the Common Terminology Criteria for Adverse Events, version 4.03. The log-rank test compared bRFS and cRFS among the modalities, and Cox regression identified factors associated with bRFS and cRFS. Gray's test compared differences in late toxicity and PSCM among the modalities. Competing risk regression identified factors associated with PCSM. Results: The median follow-up time and age were 63.5 months and 65 years, respectively. The bRFS at 5 and 10 years, respectively, was 74% and 53% for EBRT, 74% and 52% for LDR, and 65% and 47% for RP (P=.0001). The cRFS at 5 and 10 years, respectively, was 85% and 73% for EBRT, 90% and 76% for LDR, and 89% and 75% for RP (P=.121). The PCSM at 5 and 10 years, respectively, was 5.3% and 11.2% for EBRT, 3.2% and 3.6% for LDR, and 2.8% and 6.8% for RP (P=.0004). The 10-year cumulative incidence of ≥grade 3 genitourinary toxicity was 8.1% for EBRT, 7.2% for LDR, and 16.4% for RP (P<.0001). The 10-year cumulative incidence of ≥grade 3 gastrointestinal toxicity was 4.6% for EBRT, 1.1% for LDR, and 1.0% for RP (P<.0001). Conclusion: HRCaP treated with EBRT, LDR, or RP yields efficacy showing better bRFS for LDR and EBRT relative to RP, equivalence for cRFS, and a PCSM advantage of LDR and RP over EBRT. The toxicity is lowest for LDR.

  19. A Comparison Between Low-Dose-Rate Brachytherapy With or Without Androgen Deprivation, External Beam Radiation Therapy With or Without Androgen Deprivation, and Radical Prostatectomy With or Without Adjuvant or Salvage Radiation Therapy for High-Risk Prostate Cancer.

    Science.gov (United States)

    Ciezki, Jay P; Weller, Michael; Reddy, Chandana A; Kittel, Jeffrey; Singh, Harguneet; Tendulkar, Rahul; Stephans, Kevin L; Ulchaker, James; Angermeier, Kenneth; Stephenson, Andrew; Campbell, Steven; Haber, Georges-Pascal; Klein, Eric A

    2017-04-01

    We compare the efficacy and toxicity among the 3 major modalities available used to treat high-risk prostate cancer (HRCaP). From 1996 to 2012, 2557 HRCaP patients were treated: 734 received external beam radiation therapy (EBRT) with or without androgen deprivation therapy (ADT), 515 received low-dose-rate prostate brachytherapy (LDR) with or without ADT, and 1308 received radical prostatectomy (RP) with or without EBRT. Biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), and prostate cancer-specific mortality (PCSM) were assessed. Toxicity was assessed using the Common Terminology Criteria for Adverse Events, version 4.03. The log-rank test compared bRFS and cRFS among the modalities, and Cox regression identified factors associated with bRFS and cRFS. Gray's test compared differences in late toxicity and PSCM among the modalities. Competing risk regression identified factors associated with PCSM. The median follow-up time and age were 63.5 months and 65 years, respectively. The bRFS at 5 and 10 years, respectively, was 74% and 53% for EBRT, 74% and 52% for LDR, and 65% and 47% for RP (P=.0001). The cRFS at 5 and 10 years, respectively, was 85% and 73% for EBRT, 90% and 76% for LDR, and 89% and 75% for RP (P=.121). The PCSM at 5 and 10 years, respectively, was 5.3% and 11.2% for EBRT, 3.2% and 3.6% for LDR, and 2.8% and 6.8% for RP (P=.0004). The 10-year cumulative incidence of ≥grade 3 genitourinary toxicity was 8.1% for EBRT, 7.2% for LDR, and 16.4% for RP (P<.0001). The 10-year cumulative incidence of ≥grade 3 gastrointestinal toxicity was 4.6% for EBRT, 1.1% for LDR, and 1.0% for RP (P<.0001). HRCaP treated with EBRT, LDR, or RP yields efficacy showing better bRFS for LDR and EBRT relative to RP, equivalence for cRFS, and a PCSM advantage of LDR and RP over EBRT. The toxicity is lowest for LDR. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Prevention of Gynecomastia and Breast Pain Caused by Androgen Deprivation Therapy in Prostate Cancer: Tamoxifen or Radiotherapy?

    Energy Technology Data Exchange (ETDEWEB)

    Arruda Viani, Gustavo, E-mail: gusviani@gmail.com [Department of Radiation Oncology, Marilia Medical School, Marilia, Sao Paulo (Brazil); Bernardes da Silva, Lucas Godoi; Stefano, Eduardo Jose [Department of Radiation Oncology, Marilia Medical School, Marilia, Sao Paulo (Brazil)

    2012-07-15

    Purpose: To determine, in a meta-analysis, whether gynecomastia and breast pain rates in men with prostate cancer treated with androgen deprivation therapy (ADT) are reduced if treated with prophylactic radiotherapy (RT) or tamoxifen (TMX). Methods and Materials: The MEDLINE, EMBASE, CANCERLIT, and Cochrane Library databases, as well as proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing RT or TMX with observation for men with prostate cancer using ADT. Results: Six RCTs (three RT trials and three TMX trials, N = 777 patients total) were identified that met the study criteria. Pooled results from these RCTs comparing RT vs. observation showed a significant reduction in the incidence of gynecomastia and breast pain rates in patients treated with RT (odds ratio [OR] = 0.21, 95% confidence interval [CI] = 0.12-0.37, p < 0.0001, and OR = 0.34, 95% CI 0.20-0.57, p < 0.0001, respectively). Use of RT resulted in an absolute risk reduction (ARR) of 29.4% and 19.9%, with a number needed to treat (NNT) of 3.4 and 5 to avoid one case of gynecomastia and breast pain, respectively. Pooled results from trials comparing TMX vs. observation showed a statistical benefit for breast pain and gynecomastia in favor of TMX arms (OR = 0.04, 95% CI = 0.02-0.08, p < 0.0001 and OR = 0.07, 95% CI = 0.0-0.14, p < 0.00001). TMX resulted in an ARR = 64.1% and 47.6%, with an NNT of 1.56 and 2.1 to avoid one case of gynecomastia and breast pain, respectively. Considering adverse effects, TMX was 6 times more adverse effects than RT. Conclusions: Our data have shown that both TMX and RT prevented gynecomastia and breast pain in patients with prostate cancer receiving ADT for prostate cancer. Although TMX was two times more effective in preventing gynecomastia, RT should represent an effective and safe treatment option, to take into account mainly in patients with cardiovascular risk factors or thrombotic diathesis.

  1. Is Androgen Deprivation Therapy Necessary in All Intermediate-Risk Prostate Cancer Patients Treated in the Dose Escalation Era?

    Energy Technology Data Exchange (ETDEWEB)

    Castle, Katherine O., E-mail: kocastle@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hoffman, Karen E.; Levy, Lawrence B.; Lee, Andrew K.; Choi, Seungtaek; Nguyen, Quynh N.; Frank, Steven J.; Pugh, Thomas J.; McGuire, Sean E.; Kuban, Deborah A. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-03-01

    Purpose: The benefit of adding androgen deprivation therapy (ADT) to dose-escalated radiation therapy (RT) for men with intermediate-risk prostate cancer is unclear; therefore, we assessed the impact of adding ADT to dose-escalated RT on freedom from failure (FFF). Methods: Three groups of men treated with intensity modulated RT or 3-dimensional conformal RT (75.6-78 Gy) from 1993-2008 for prostate cancer were categorized as (1) 326 intermediate-risk patients treated with RT alone, (2) 218 intermediate-risk patients treated with RT and ≤6 months of ADT, and (3) 274 low-risk patients treated with definitive RT. Median follow-up was 58 months. Recursive partitioning analysis based on FFF using Gleason score (GS), T stage, and pretreatment PSA concentration was applied to the intermediate-risk patients treated with RT alone. The Kaplan-Meier method was used to estimate 5-year FFF. Results: Based on recursive partitioning analysis, intermediate-risk patients treated with RT alone were divided into 3 prognostic groups: (1) 188 favorable patients: GS 6, ≤T2b or GS 3+4, ≤T1c; (2) 71 marginal patients: GS 3+4, T2a-b; and (3) 68 unfavorable patients: GS 4+3 or T2c disease. Hazard ratios (HR) for recurrence in each group were 1.0, 2.1, and 4.6, respectively. When intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT, the greatest benefit from ADT was seen for the unfavorable intermediate-risk patients (FFF, 74% vs 94%, respectively; P=.005). Favorable intermediate-risk patients had no significant benefit from the addition of ADT to RT (FFF, 94% vs 95%, respectively; P=.85), and FFF for favorable intermediate-risk patients treated with RT alone approached that of low-risk patients treated with RT alone (98%). Conclusions: Patients with favorable intermediate-risk prostate cancer did not benefit from the addition of ADT to dose-escalated RT, and their FFF was nearly as good as patients with low-risk disease

  2. Favorable outcomes in locally advanced and node positive prostate cancer patients treated with combined pelvic IMRT and androgen deprivation therapy

    International Nuclear Information System (INIS)

    Lilleby, Wolfgang; Narrang, Amol; Tafjord, Gunnar; Vlatkovic, Ljiljana; Russnes, Kjell Magne; Stensvold, Andreas; Hole, Knut Håkon; Tran, Phuoc; Eilertsen, Karsten

    2015-01-01

    The most appropriate treatment for men with prostate cancer and positive pelvic nodes, N+, is an area of active controversy. We report our 5-years outcomes in men with locally advanced prostate cancer (T1-T4N0-N1M0) treated with definitive radiotherapy encompassing the prostate and pelvic lymph nodes (intensity modulated radiotherapy, IMRT) and long-term androgen deprivation therapy (ADT). Of the 138 consecutive eligible men all living patients have been followed up to almost 5 years. Survival endpoints for 5-year biochemical failure-free survival (BFFS), relapse-free survival (RFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were assessed by Kaplan-Meier analysis. Univariate and multivariate Cox regression proportional hazards models were constructed for all survival endpoints. The RTOG morbidity grading system for physician rated toxicity was applied. Patients with locally advanced T3-T4 tumors (35 %) and N1 (51 %) have favorable outcome when long-term ADT is combined with definitive radiotherapy encompassing pelvic lymph nodes. The 5-year BFFS, RFS, PCSS and OS were 71.4, 76.2, 94.5 and 89.0 %, respectively. High Gleason sum (9–10) had a strong independent prognostic impact on BFFS, RFS and OS (p = 0.001, <0.001, and 0.005 respectively). The duration of ADT (= > 28 months) showed a significant independent association with improved PCSS (p = 0.02) and OS (p = 0.001). Lymph node involvement was not associated with survival endpoints in the multivariate analysis. The radiotherapy induced toxicity seen in our study population was moderate with rare Grade 3 GI side effects and up to 11 % for Grade 3 GU consisting mainly of urgency and frequency. Pelvic IMRT in combination with long-term ADT can achieve long-lasting disease control in men with N+ disease and unfavorable prognostic factors. The online version of this article (doi:10.1186/s13014-015-0540-3) contains supplementary material, which is available to authorized users

  3. Biochemical failure and the temporal kinetics of prostate-specific antigen after radiation therapy with androgen deprivation

    International Nuclear Information System (INIS)

    Buyyounouski, Mark K.; Hanlon, Alexandra L.; Horwitz, Eric M.; Uzzo, Robert G.; Pollack, Alan

    2005-01-01

    Purpose: The accuracy of the American Society of Therapeutic Radiation Oncology consensus definition of biochemical failure (BF) after radiation therapy (RT) and androgen deprivation (AD) has been questioned, because posttreatment prostate-specific antigen (PSA) levels typically rise after release from AD, and misclassification of BF may be made. The temporal kinetics of posttreatment PSA levels was examined to define the error in the classification of BF. Methods and Materials: Between December 1, 1991 and April 30, 1998, 688 men with T1c-T3 NX/0 M0 prostate cancer received three-dimensional conformal RT alone (n = 586) or in combination with either short-term (STAD: 3 to 12 months, n = 82) or long-term (LTAD: 12 to 36 months, n = 20) AD. Follow-up, calculated from the end of all treatment, was ≥48 months. The mean posttreatment PSA was calculated in 3-month intervals. Results: The median posttreatment clinical follow-up period was 76 months (range, 48-152 months). The posttreatment PSA values from the end of all treatment for the RT+STAD-BF group showed an initial period of rise followed by a period of decline at 30 months and then a continued rise again. The decline in the mean posttreatment PSA is explained in part by stabilization in PSA level after 3 consecutive rises. Nonbiochemical failures (NBF) after RT+STAD had a relatively constant mean PSA over time of approximately 0.5 ng/mL. Unlike the RT+STAD-NBF profile, the RT+LTAD-NBF profile rose continuously and steadily to a level approaching 1 ng/mL. The RT+LTAD-BF profile rose continuously but at a slower rate over time. Nine RT+STAD-NBF patients (22%) and 2 RT+LTAD-BF (29%) patients experienced 3 consecutive rises followed by a subsequent decline and stabilization of PSA compared to 10 RT-BF patients (5%). Redistributing these misclassified patients to their respective NBF groups changed the mean posttreatment PSA profiles as follows: The RT+LTAD-BF profile rose constantly and steadily with a doubling

  4. Intensity-Modulated Radiotherapy Reduces Gastrointestinal Toxicity in Patients Treated With Androgen Deprivation Therapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Sharma, Navesh K.; Li Tianyu; Chen, David Y.; Pollack, Alan; Horwitz, Eric M.; Buyyounouski, Mark K.

    2011-01-01

    Purpose: Androgen deprivation therapy (AD) has been shown to increase late Grade 2 or greater rectal toxicity when used concurrently with three-dimensional conformal radiotherapy (3D-CRT). Intensity-modulated radiotherapy (IMRT) has the potential to reduce toxicity by limiting the radiation dose received by the bowel and bladder. The present study compared the genitourinary and gastrointestinal (GI) toxicity in men treated with 3D-CRT+AD vs. IMRT+AD. Methods and Materials: Between July 1992 and July 2004, 293 men underwent 3D-CRT (n = 170) or IMRT (n = 123) with concurrent AD (<6 months, n = 123; ≥6 months, n = 170). The median radiation dose was 76 Gy for 3D-CRT (International Commission on Radiation Units and Measurements) and 76 Gy for IMRT (95% to the planning target volume). Toxicity was assessed by a patient symptom questionnaire that was completed at each visit and recorded using a Fox Chase Modified Late Effects Normal Tissue Task radiation morbidity scale. Results: The mean follow-up was 86 months (standard deviation, 29.3) for the 3D-CRT group and 40 months (standard deviation, 9.7) for the IMRT group. Acute GI toxicity (odds ratio, 4; 95% confidence interval, 1.6-11.7; p = .005) was significantly greater with 3D-CRT than with IMRT and was independent of the AD duration (i.e., <6 vs. ≥6 months). The interval to the development of late GI toxicity was significantly longer in the IMRT group. The 5-year Kaplan-Meier estimate for Grade 2 or greater GI toxicity was 20% for 3D-CRT and 8% for IMRT (p = .01). On multivariate analysis, Grade 2 or greater late GI toxicity (hazard ratio, 2.1; 95% confidence interval, 1.1-4.3; p = .04) was more prevalent in the 3D-CRT patients. Conclusion: Compared with 3D-CRT, IMRT significantly decreased the acute and late GI toxicity in patients treated with AD.

  5. Exercise Improves V˙O2max and Body Composition in Androgen Deprivation Therapy-treated Prostate Cancer Patients.

    Science.gov (United States)

    Wall, Bradley A; GALVãO, Daniel A; Fatehee, Naeem; Taaffe, Dennis R; Spry, Nigel; Joseph, David; Hebert, Jeffrey J; Newton, Robert U

    2017-08-01

    Prostate cancer is the most common cancer in men, and patients treated with androgen deprivation therapy (ADT) experience unfavorable changes in body composition and associated metabolic complications, which can increase the risk of cardiovascular disease. We examined the effect of a 6-month program of aerobic and resistance exercise aimed at improving body composition and cardiorespiratory health in this population. Ninety-seven men (43-90 yr) with localized prostate cancer receiving ADT were randomized to either exercise (EX, n = 50) or usual care (CON, n = 47). Supervised exercise was undertaken twice weekly at moderate to high intensity. Measures of cardiorespiratory capacity (V˙O2max), resting metabolic rate, central blood pressure, hemodynamic variables, blood markers, and body composition were assessed. There was a significant group-time interaction present for V˙O2max (P = 0.033) with a treatment effect for EX of 0.11 L·min (95% confidence interval [CI] = 0.04-0.19) (relative to body mass = 1.3 mL·kg·min, 95% CI = 0.3-2.3) and fat oxidation (P = 0.037) of 12.0 mg·min (95% CI = 2.3-21.7). Similarly, there was a significant improvement in glucose (P < 0.001) for EX of -0.5 mmol·L (95% CI = -0.8 to -0.3), with no change in prostate-specific antigen or testosterone as a result of exercise. Body composition was enhanced for EX with adjusted mean differences in lean mass (P = 0.015) of 0.8 kg (95% CI = 0.3-1.3), total fat mass (P = 0.020) of -1.1 kg (95% CI = -1.8 to -0.5), and trunk fat mass (P < 0.001) of -1.0 kg (95% CI = -1.4 to -0.6). A 6-month combined aerobic and resistance exercise program has a significant favorable effect on cardiorespiratory capacity, resting fat oxidation, glucose, and body composition despite the adverse effects of hormone suppression. Combined aerobic and resistance training should be considered a key adjuvant component in men undergoing ADT for the treatment of prostate cancer.

  6. Riscos cardiovasculares do bloqueio androgênico Riesgos cardiovasculares del bloqueo androgénico Cardiovascular risks of androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Adriano Freitas Ribeiro

    2010-09-01

    Full Text Available O adenocarcinoma de próstata é o câncer mais comum no sexo masculino após o câncer de pele. Entre as várias formas de tratamento do câncer de próstata, a terapia de bloqueio androgênico é uma modalidade consagrada nos pacientes com doença metastática ou localmente avançada, que provavelmente resulta em aumento de sobrevida. No entanto, o bloqueio androgênico é causador de uma série de consequências adversas. Complicações como osteoporose, disfunção sexual, ginecomastia, anemia e alterações na composição corporal são bem conhecidas. Recentemente, uma série de complicações metabólicas foi descrita como aumento da circunferência abdominal, resistência à insulina, hiperglicemia, diabete, dislipidemia e síndrome metabólica com consequente aumento do risco de eventos coronarianos e mortalidade cardiovascular nessa população específica. Este artigo de atualização apresenta uma revisão bibliográfica realizada no MEDLINE de toda literatura publicada em inglês no período de 1966 até junho de 2009, com as seguintes palavras-chave: androgen deprivation therapy, androgen supression therapy, hormone treatment, prostate cancer, metabolic syndrome e cardiovascular disease, no intuito de analisar quais seriam os reais riscos cardiovasculares da terapia de deprivação androgênica, também chamada bloqueio androgênico, nos pacientes com câncer de próstata.El adenocarcinoma de próstata es el cáncer más común en el sexo masculino después del cáncer de piel. Entre las varias formas de tratamiento del cáncer de próstata, la terapia de bloqueo androgénico es una modalidad consagrada en los pacientes con enfermedad metastásica o localmente avanzada, que probablemente resulta en aumento de sobrevida. Mientras tanto, el bloqueo androgénico es causante de una serie de consecuencias adversas. Complicaciones como osteoporosis, disfunción sexual, ginecomastia, anemia y alteraciones en la composición corporal son

  7. Combined curative radiotherapy including HDR brachytherapy and androgen deprivation in localized prostate cancer: A prospective assessment of acute and late treatment toxicity

    International Nuclear Information System (INIS)

    Wahlgren, Thomas; Nilsson, Sten; Ryberg, Marianne; Brandberg, Yvonne; Lennernaes, Bo

    2005-01-01

    Self-reported symptoms including urinary, bowel and sexual side effects were investigated prospectively at multiple assessment points before and after combined radiotherapy of prostate cancer including HDR brachytherapy and neoadjuvant androgen deprivation therapy. Between April 2000 and June 2003, patients with predominantly advanced localized prostate tumours subjected to this treatment were asked before treatment and on follow-up visits to complete a questionnaire covering urinary, bowel and sexual problems. The mainly descriptive analyses included 525 patients, responding to at least one questionnaire before or during the period 2-34 months after radiotherapy. Adding androgen deprivation before radiotherapy significantly worsened sexual function. During radiotherapy, urinary, bowel and sexual problems increased and were reported at higher levels up to 34 months, although there seemed to be a general tendency to less pronounced irritative bowel and urinary tract symptoms over time. No side effects requiring surgery were reported. Classic late irradiation effects such as mucosal bleeding were demonstrated mainly during the second year after therapy, but appear less pronounced in comparison with dose escalated EBRT series. In conclusion, despite the high radiation dose given, the toxicity seemed comparable with that of other series but long term (5-10 years) symptom outcome has to be determined

  8. The impact of androgen deprivation therapy on setup errors during external beam radiation therapy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Onal, Cem; Dolek, Yemliha; Ozdemir, Yurday [Baskent University, Faculty of Medicine, Adana Dr. Turgut Noyan Research and Treatment Centre, Department of Radiation Oncology, Adana (Turkey)

    2017-06-15

    To determine whether setup errors during external beam radiation therapy (RT) for prostate cancer are influenced by the combination of androgen deprivation treatment (ADT) and RT. Data from 175 patients treated for prostate cancer were retrospectively analyzed. Treatment was as follows: concurrent ADT plus RT, 33 patients (19%); neoadjuvant and concurrent ADT plus RT, 91 patients (52%); RT only, 51 patients (29%). Required couch shifts without rotations were recorded for each megavoltage (MV) cone beam computed tomography (CBCT) scan, and corresponding alignment shifts were recorded as left-right (x), superior-inferior (y), and anterior-posterior (z). The nonparametric Mann-Whitney test was used to compare shifts by group. Pearson's correlation coefficient was used to measure the correlation of couch shifts between groups. Mean prostate shifts and standard deviations (SD) were calculated and pooled to obtain mean or group systematic error (M), SD of systematic error (Σ), and SD of random error (σ). No significant differences were observed in prostate shifts in any direction between the groups. Shifts on CBCT were all less than setup margins. A significant positive correlation was observed between prostate volume and the z-direction prostate shift (r = 0.19, p = 0.04), regardless of ADT group, but not between volume and x- or y-direction shifts (r = 0.04, p = 0.7; r = 0.03, p = 0.7). Random and systematic errors for all patient cohorts and ADT groups were similar. Hormone therapy given concurrently with RT was not found to significantly impact setup errors. Prostate volume was significantly correlated with shifts in the anterior-posterior direction only. (orig.) [German] Ziel war zu untersuchen, ob Konfigurationsfehler bei der externen Radiotherapie (RT) des Prostatakarzinoms durch die Kombination aus Androgendeprivationstherapie (ADT) und RT beeinflusst werden. Retrospektiv wurden die Daten von 175 wegen eines Prostatakarzinoms behandelten Patienten

  9. Three linked nomograms for predicting biochemical failure in prostate cancer treated with radiotherapy plus androgen deprivation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Torrecilla, Jose [Hospital General Universitario, Servicio Oncologia Radioterapica- ERESA, Valencia (Spain); Boladeras, Anna [Institut Catala d' Oncologia, S.Oncologia Radioterapica, Hospitalet (Spain); Angeles Cabeza, Maria [Hospital Universitario Doce de Octubre, S.Oncologia Radioterapica, Madrid (Spain); Zapatero, Almudena [Hospital Universitario de la Princesa, S.Oncologia Radioterapica, Madrid (Spain); Jove, Josep [Institut Catala d' Oncologia, S.Oncologia Radioterapica, Badalona (Spain); Esteban, Luis M. [Universidad de Zaragoza, Escuela Universitaria Politecnica de La Almunia, Zaragoza (Spain); Henriquez, Ivan [Hospital Universitari Sant Joan de Reus, S.Oncologia Radioterapica, Reus (Spain); Casana, Manuel; Mengual, Jose Luis [Fundacion Instituto Valenciano de Oncologia, S.Oncologia Radioterapica, Valencia (Spain); Gonzalez-San Segundo, Carmen [Hospital Universitario Gregorio Maranon, S.Oncologia Radioterapica, Madrid (Spain); Gomez-Caamano, Antonio [Hospital Clinico Universitario de Santiago, S.Oncologia Radioterapica, Santiago de Compostela (Spain); Hervas, Asuncion [Hospital Universitario Ramon y Cajal, S.Oncologia Radioterapica, Madrid (Spain); Munoz, Julia Luisa [Hospital Infanta Cristina, S.Oncologia Radioterapica, Badajoz (Spain); Sanz, Gerardo [Universidad de Zaragoza, Departamento de Metodos Estadisticos, Zaragoza (Spain)

    2015-10-15

    Nomograms were established to predict biochemical recurrence (BCR) after radiotherapy (RT) with a low weight of the characteristic variables of RT and androgen deprivation therapy (ADT). Our aim is to provide a new stratified tool for predicting BCR at 4 and 7 years in patients treated using RT with radical intent. A retrospective, nonrandomized analysis was performed on 5044 prostate cancer (PCa) patients with median age 70 years, who received RT - with or without ADT - between November 1992 and May 2007. Median follow-up was 5.5 years. BCR was defined as a rise in serum prostate-specific antigen (PSA) of 2 ng/ml over the post-treatment PSA nadir. Univariate association between predictor variables and BCR was assessed by the log-rank test, and three linked nomograms were created for multivariate prognosis of BCR-free survival. Each nomogram corresponds to a category of the Gleason score - either 6,7, or 8-10 - and all of them were created from a single proportional hazards regression model stratified also by months of ADT (0, 1-6, 7-12, 13-24, 25-36, 36-60). The performance of this model was analyzed by calibration, discrimination, and clinical utility. Initial PSA, clinical stage, and RT dose were significant variables (p < 0.01). The model showed a good calibration. The concordance probability was 0.779, improving those obtained with other nomograms (0.587, 0.571, 0.554) in the database. Survival curves showed best clinical utility in a comparison with National Comprehensive Cancer Network (NCCN) risk groups. For each Gleason score category, the nomogram provides information on the benefit of adding ADT to a specific RT dose. (orig.) [German] Es wurden Nomogramme etabliert, um ein biochemisches Rezidiv (BCR) nach einer Strahlentherapie (RT) vorhersagen zu koennen und den Einfluss der charakteristischen Variablen der RT und der Androgendeprivationstherapie (ADT) dabei moeglichst gering zu halten. Unser Ziel ist es, ein neues stratifiziertes Instrument

  10. Obesity is associated with castration-resistant disease and metastasis in men treated with androgen deprivation therapy after radical prostatectomy: results from the SEARCH database.

    Science.gov (United States)

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

    2012-08-01

    Study Type - Prognosis (cohort series). Level of Evidence 2a. What's known on the subject? and What does the study add? The incidence and prevalence of obesity in the USA and Europe is increasing. Higher body mass index is associated with a lower risk of overall prostate cancer diagnosis but also with an increased risk of high grade prostate cancer. Obese men undergoing primary therapy with radical prostatectomy or external beam radiation are more likely to experience a biochemical recurrence after treatment compared with normal weight men. Finally, obesity is associated with increased prostate-cancer-specific mortality. We hypothesized that obese men on androgen deprivation therapy may be at increased risk for prostate cancer progression. Previous studies have shown that obese men have lower levels of testosterone compared with normal weight men. Additionally, one previous study found that obese men have higher levels of testosterone on androgen deprivation therapy. Men with higher levels of testosterone on androgen deprivation therapy are at increased risk of prostate cancer progression. We found that men with higher body mass index were at increased risk of progression to castration-resistant prostate cancer, development of metastases and prostate-cancer-specific mortality. When we adjusted for various clinicopathological characteristics, obese men were at increased risk of progression to castration-resistant prostate cancer and development of metastases. The results of our study help generate hypotheses for further study regarding the mechanisms between obesity and aggressive prostate cancer. • To investigate whether obesity predicts poor outcomes in men starting androgen deprivation therapy (ADT) before metastasis, since previous studies found worse outcomes after surgery and radiation for obese men. • A retrospective review was carried out of 287 men in the SEARCH database treated with radical prostatectomy between 1988 and 2009. • Body mass index (BMI

  11. Cardiovascular Adaptations to Recreational Football Training in Men with Type 2 Diabetes, Untrained Elderly Men and in Men with Prostate Cancer Receiving Androgen Deprivation Therapy

    DEFF Research Database (Denmark)

    Schmidt, Jakob Friis

    untrained men and in veteran football players encouraging results were observed. In conclusion, the present PhD thesis revealed that football training is a feasible alternative exercise training modality, which is associated with improved cardiovascular health in the examined populations.......Numerous people in the general population are not suffuciently physically active and the use of new exercise training modalities which could promote physically active lifestyles are important. The present PhD thesis includes studies , which investigated the effect of recreational football training...... in middle-aged men with type 2 diabetes, 65-75-year-old untrained men, men with prostate cancer receiving androgen deprivation therapy and the effect of life-long participation in football training in veteran football players. The primary purpose was to evaluate the structure and function of the heart...

  12. Effects of Different Exercise Modalities on Fatigue in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: A Year-long Randomised Controlled Trial.

    Science.gov (United States)

    Taaffe, Dennis R; Newton, Robert U; Spry, Nigel; Joseph, David; Chambers, Suzanne K; Gardiner, Robert A; Wall, Brad A; Cormie, Prue; Bolam, Kate A; Galvão, Daniel A

    2017-08-01

    Physical exercise mitigates fatigue during androgen deprivation therapy (ADT); however, the effects of different exercise prescriptions are unknown. To determine the long-term effects of different exercise modes on fatigue in prostate cancer patients undergoing ADT. Between 2009 and 2012, 163 prostate cancer patients aged 43-90 y on ADT were randomised to exercise targeting the musculoskeletal system (impact loading+resistance training; ILRT; n=58), the cardiovascular and muscular systems (aerobic+resistance training; ART; n=54), or to usual care/delayed exercise (DEL; n=51) for 12 mo across university-affiliated exercise clinics in Australia. Supervised ILRT for 12 mo, supervised ART for 6 mo followed by a 6-mo home program, and DEL received a printed booklet on exercise information for 6 mo followed by 6-mo stationary cycling exercise. Fatigue was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 36 and vitality using the Short Form-36. Analysis of variance was used to compare outcomes for groups at 6 mo and 12 mo. Fatigue was reduced (p=0.005) in ILRT at 6 mo and 12 mo (∼5 points), and in ART (p=0.005) and DEL (p=0.022) at 12 mo. Similarly, vitality increased for all groups (p≤0.001) at 12 mo (∼4 points). Those with the highest levels of fatigue and lowest vitality improved the most with exercise (p trend exercise modes have comparable effects on reducing fatigue and enhancing vitality during ADT. Patients with the highest levels of fatigue and lowest vitality had the greatest benefits. We compared the effects of different exercise modes on fatigue in men on androgen deprivation therapy. All exercise programs reduced fatigue and enhanced vitality. We conclude that undertaking some form of exercise will help reduce fatigue, especially in those who are the most fatigued. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  13. Clinical outcomes and nadir prostate-specific antigen (PSA) according to initial PSA levels in primary androgen deprivation therapy for metastatic prostate cancer.

    Science.gov (United States)

    Kitagawa, Yasuhide; Ueno, Satoru; Izumi, Kouji; Kadono, Yoshifumi; Mizokami, Atsushi; Hinotsu, Shiro; Akaza, Hideyuki; Namiki, Mikio

    2016-03-01

    To investigate the clinical outcomes of metastatic prostate cancer patients and the relationship between nadir prostate-specific antigen (PSA) levels and different types of primary androgen deprivation therapy (PADT). This study utilized data from the Japan Study Group of Prostate Cancer registry, which is a large, multicenter, population-based database. A total of 2982 patients treated with PADT were enrolled. Kaplan-Meier analysis was used to compare progression-free survival (PFS) and overall survival (OS) in patients treated using combined androgen blockade (CAB) and non-CAB therapies. The relationships between nadir PSA levels and PADT type according to initial serum PSA levels were also investigated. Among the 2982 enrolled patients, 2101 (70.5 %) were treated with CAB. Although CAB-treated patients had worse clinical characteristics, their probability of PFS and OS was higher compared with those treated with a non-CAB therapy. These results were due to a survival benefit with CAB in patients with an initial PSA level of 500-1000 ng/mL. Nadir PSA levels were significantly lower in CAB patients than in non-CAB patients with comparable initial serum PSA levels. A small survival benefit for CAB in metastatic prostate cancer was demonstrated in a Japanese large-scale prospective cohort study. The clinical significance of nadir PSA levels following PADT was evident, but the predictive impact of PSA nadir on OS was different between CAB and non-CAB therapy.

  14. SLCO2B1 and SLCO1B3 as New Targets for Enhancing Androgen Deprivation Therapy for Prostate Cancer

    Science.gov (United States)

    2015-10-01

    Wang Y-K, Charng M-J, Ueng Y-F. Determination of serum atorvastatin concentrations in lipid-controlling patients with and without myalgia syndrome ...specific antigen levels: analysis of the National Health and Nutrition Examination Survey. Journal of clinical oncology : official journal of the...in prostate cancer. Curr Opin Oncol 24:251-7, 2012 6. Mostaghel EA, Nelson PS: Intracrine androgen metabolism in prostate cancer progression

  15. External beam radiation therapy and a low-dose-rate brachytherapy boost without or with androgen deprivation therapy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Strom, Tobin J.; Hutchinson, Sean Z.; Shrinath, Kushagra; Cruz, Alex A.; Figura, Nicholas B.; Nethers, Kevin; Biagioli, Matthew C.; Fernandez, Daniel C.; Heysek, Randy V.; Wilder, Richard B., E-mail: richard.wilder@moffitt.org [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States)

    2014-07-15

    Purpose: To assess outcomes with external beam radiation therapy (EBRT) and a low-dose-rate (LDR) brachytherapy boost without or with androgen deprivation therapy (ADT) for prostate cancer. Materials and Methods: From January 2001 through August 2011, 120 intermediate-risk or high-risk prostate cancer patients were treated with EBRT to a total dose of 4,500 cGy in 25 daily fractions and a palladium-103 LDR brachytherapy boost of 10,000 cGy (n = 90) or an iodine-125 LDR brachytherapy boost of 11,000 cGy (n = 30). ADT, consisting of a gonadotropin-releasing hormone agonist ± an anti-androgen, was administered to 29/92 (32%) intermediate-risk patients for a median duration of 4 months and 26/28 (93%) high-risk patients for a median duration of 28 months. Results: Median follow-up was 5.2 years (range, 1.1-12.8 years). There was no statistically-significant difference in biochemical disease-free survival (bDFS), distant metastasis-free survival (DMFS), or overall survival (OS) without or with ADT. Also, there was no statistically-significant difference in bDFS, DMFS, or OS with a palladium-103 vs. an iodine-125 LDR brachytherapy boost. Conclusions: There was no statistically-significant difference in outcomes with the addition of ADT, though the power of the current study was limited. The Radiation Therapy Oncology Group 0815 and 0924 phase III trials, which have accrual targets of more than 1,500 men, will help to clarify the role ADT in locally-advanced prostate cancer patients treated with EBRT and a brachytherapy boost. Palladium-103 and iodine-125 provide similar bDFS, DMFS, and OS. (author)

  16. A phase II RCT and economic analysis of three exercise delivery methods in men with prostate cancer on androgen deprivation therapy.

    Science.gov (United States)

    Alibhai, Shabbir M H; Santa Mina, Daniel; Ritvo, Paul; Sabiston, Catherine; Krahn, Murray; Tomlinson, George; Matthew, Andrew; Segal, Roanne; Warde, Padraig; Durbano, Sara; O'Neill, Meagan; Culos-Reed, Nicole

    2015-04-25

    Androgen deprivation therapy is commonly used to treat prostate cancer, the most common visceral cancer in men. However, various side effects often worsen physical functioning and reduce well-being among men on this treatment. Based on existing evidence, both resistance and aerobic training provide benefits for this population yet adherence rates are often low. The method of exercise delivery (supervised in-center or home-based) may be important, yet few studies have compared different models. Additionally, long-term exercise adherence is critical to achieve sustained benefits but long-term adherence data and predictors of adherence are lacking. The primary aim of this phase II, non-inferiority randomized controlled trial is to determine whether three exercise training delivery models are equivalent in terms of benefits in quality of life and physical fitness in this population. Secondary aims include examination of long-term adherence and cost-effectiveness. Men diagnosed with prostate cancer, starting or continuing on androgen deprivation therapy for at least 6 months, fluent in English, and living close to one of two experienced Canadian study centers are eligible. Participants complete five assessments over one year, including a fitness assessment and self-report questionnaires. Socio-demographic and clinical data collection occur at baseline, bone mineral density testing at two time points, and blood work is performed at three time points. Participants are randomized in a 1:1:1 fashion to supervised personal training, supervised group training, or home-based smartphone- and health coach-supported training. Each participant receives a detailed exercise manual, including illustrations of exercises and safety precautions. Participants are asked to complete 4 to 5 exercise sessions per week, incorporating aerobic, resistance and flexibility training. Participant intensity levels will be monitored. The intervention duration is 6 months, with 6 months additional

  17. A randomised controlled trial to evaluate the efficacy of a 6 month dietary and physical activity intervention for prostate cancer patients receiving androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Haseen Farhana

    2010-08-01

    Full Text Available Abstract Background Treatment with Androgen Deprivation Therapy (ADT for prostate cancer is associated with changes in body composition including increased fat and decreased lean mass; increased fatigue, and a reduction in quality of life. No study to date has evaluated the effect of dietary and physical activity modification on the side-effects related to ADT. The aim of this study is to evaluate the efficacy of a 6-month dietary and physical activity intervention for prostate cancer survivors receiving ADT to minimise the changes in body composition, fatigue and quality of life, typically associated with ADT. Methods Men are recruited to this study if their treatment plan is to receive ADT for at least 6 months. Men who are randomised to the intervention arm receive a home-based tailored intervention to meet the following guidelines a ≥ 5 servings vegetables and fruits/day; b 30%-35% of total energy from fat, and Discussion The results of this study will provide detailed information on diet and physical activity levels in prostate cancer patients treated with ADT and will test the feasibility and efficacy of a diet and physical activity intervention which could provide essential information to develop guidelines for prostate cancer patients to minimise the side effects related to ADT. Trial registration ISRCTN trial number ISCRTN75282423

  18. Multi-institutional Evaluation of Elective Nodal Irradiation and/or Androgen Deprivation Therapy with Postprostatectomy Salvage Radiotherapy for Prostate Cancer.

    Science.gov (United States)

    Ramey, Stephen J; Agrawal, Shree; Abramowitz, Matthew C; Moghanaki, Drew; Pisansky, Thomas M; Efstathiou, Jason A; Michalski, Jeff M; Spratt, Daniel E; Hearn, Jason W D; Koontz, Bridget F; Liauw, Stanley L; Pollack, Alan; Anscher, Mitchell S; Den, Robert B; Stephans, Kevin L; Zietman, Anthony L; Lee, W Robert; Stephenson, Andrew J; Tendulkar, Rahul D

    2017-11-09

    Outcomes with postprostatectomy salvage radiation therapy (SRT) are not ideal. Little evidence exists regarding potential benefits of adding whole pelvic radiation therapy (WPRT) alone or in combination with androgen deprivation therapy (ADT). To explore whether WPRT and/or ADT added to prostate bed radiation therapy (PBRT) improves freedom from biochemical failure (FFBF) or distant metastases (DM). A database was compiled from 10 academic institutions of patients with postprostatectomy prostate-specific antigen (PSA) >0.01 ng/ml; pT1-4, Nx/0, cM0; and Gleason score (GS) ≥7 treated between 1987 and 2013. Median follow-up was 51 mo. WPRT and/or ADT in addition to PBRT. FFBF and DM were calculated using cumulative incidence estimation. Multivariable analysis (MVA) utilized cumulative incidence regression. Median pre-SRT PSA was 0.5 ng/ml for 1861 patients. Median follow-up for patients not experiencing biochemical failure (BF) was 55 mo. MVA showed increased BF for PBRT versus WPRT (hazard ratio [HR] 1.82, pevaluated patients with prostate cancer treated with radiation after surgery to remove the prostate. Both radiation to the pelvic lymph nodes and suppression of testosterone lowered the chance of increasing prostate-specific antigen (a marker for cancer returning). Copyright © 2017 European Association of Urology. All rights reserved.

  19. Spinal multiparametric MRI and DEXA changes over time in men with prostate cancer treated with androgen deprivation therapy: a potential imaging biomarker of treatment toxicity

    International Nuclear Information System (INIS)

    Martin, Jarad; Arm, Jameen; Smart, Joanne; Palazzi, Kerrin; Capp, Anne; Ainsworth, Paul; Cowin, Gary

    2017-01-01

    To explore changes in bone mineral density (BMD) measured by DEXA and MRS fat fraction (FF), Dixon FF, and ADC in lower spinal vertebral bodies in men with prostate cancer treated with androgen deprivation therapy (ADT). Twenty-eight men were enrolled onto a clinical trial. All received ADT. DEXA imaging was performed at baseline and 12 months. L-spine MRI was done at baseline and 6 months. The number of patients who underwent DEXA, Dixon, ADC, and MRS at baseline/follow-up were 28/27, 28/26, 28/26, and 22/20. An increase in FF was observed from T11 to S2 (average 1 %/vertebra). There was a positive correlation between baseline MRS FF and Dixon FF (r = 0.85, p < 0.0001) and a negative correlation between MRS FF and ADC (r = -0.56, p = 0.036). Over 6 months, MRS FF increased by a median of 25 % in relative values (p = 0.0003), Dixon FF increased (p < 0.0001) and ADC values decreased (p = 0.0014). Men with >5 % BMD loss after 1 year had triple the percentage increase in MRS FF at 6 months (61.1 % vs. 20.9 %, p = 0.19). Changes are observed on L-spine MRI after 6 months of ADT. Further investigation is warranted of MRS change as a potential predictive biomarker for later BMD loss. (orig.)

  20. Spinal multiparametric MRI and DEXA changes over time in men with prostate cancer treated with androgen deprivation therapy: a potential imaging biomarker of treatment toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Jarad [Calvary Mater Newcastle, Department of Radiation Oncology, Newcastle, New South Wales (Australia); University of Newcastle, School of Medicine and Public Health, Newcastle, New South Wales (Australia); University of Queensland, Centre for Advanced Imaging, Brisbane, Queensland (Australia); Arm, Jameen [Hunter New England Imaging, Newcastle, New South Wales (Australia); Smart, Joanne [Calvary Mater Newcastle, Department of Radiation Oncology, Newcastle, New South Wales (Australia); Palazzi, Kerrin [CREDITSS, Hunter Medical Research Institute, Newcastle, New South Wales (Australia); Capp, Anne [Calvary Mater Newcastle, Department of Radiation Oncology, Newcastle, New South Wales (Australia); University of Newcastle, School of Medicine and Public Health, Newcastle, New South Wales (Australia); Ainsworth, Paul [Hunter New England Health, Department of Urology, Newcastle, New South Wales (Australia); Cowin, Gary [University of Queensland, Centre for Advanced Imaging, Brisbane, Queensland (Australia)

    2017-03-15

    To explore changes in bone mineral density (BMD) measured by DEXA and MRS fat fraction (FF), Dixon FF, and ADC in lower spinal vertebral bodies in men with prostate cancer treated with androgen deprivation therapy (ADT). Twenty-eight men were enrolled onto a clinical trial. All received ADT. DEXA imaging was performed at baseline and 12 months. L-spine MRI was done at baseline and 6 months. The number of patients who underwent DEXA, Dixon, ADC, and MRS at baseline/follow-up were 28/27, 28/26, 28/26, and 22/20. An increase in FF was observed from T11 to S2 (average 1 %/vertebra). There was a positive correlation between baseline MRS FF and Dixon FF (r = 0.85, p < 0.0001) and a negative correlation between MRS FF and ADC (r = -0.56, p = 0.036). Over 6 months, MRS FF increased by a median of 25 % in relative values (p = 0.0003), Dixon FF increased (p < 0.0001) and ADC values decreased (p = 0.0014). Men with >5 % BMD loss after 1 year had triple the percentage increase in MRS FF at 6 months (61.1 % vs. 20.9 %, p = 0.19). Changes are observed on L-spine MRI after 6 months of ADT. Further investigation is warranted of MRS change as a potential predictive biomarker for later BMD loss. (orig.)

  1. Evaluation of the efficacy and safety of Salvia officinalis in controlling hot flashes in prostate cancer patients treated with androgen deprivation.

    Science.gov (United States)

    Vandecasteele, Katrien; Ost, Piet; Oosterlinck, Willem; Fonteyne, Valérie; Neve, Wilfried De; Meerleer, Gert De

    2012-02-01

    The purpose of this pilot study was to evaluate the efficacy and safety of Salvia officinalis in controlling hot flashes in prostate cancer patients treated with androgen deprivation therapy (ADT). Ten patients experiencing hot flashes were included in a single-centre prospective pilot study. Treatment consisted of 150 mg of Salvia officinalis extract taken orally three times daily. A diary questionnaire scoring hot flashes, subjective side effects and quality of life (QOL) had to be completed. Clinical examination was performed at every visit and the concentration of ADT-linked hormones, haemoglobin and cholesterol was measured before, during and after ending treatment. Before the start of treatment, a 1 week baseline registration was performed. An analysis of variance with time of measurement as a within-subject factor was performed. When analysing the hot flashes score, one patient was excluded due to insufficient diary notes. The mean weekly score declined from 112 (SD = 71) at baseline to 59 (SD = 54) at the end of treatment (p = 0.002). Hot flashes diminished significantly from the first week up to and including week 3. This was maintained during treatment. There was no effect on QOL. There were no side effects. It is concluded that Salvia officinalis is efficient and safe in the treatment hot flashes, without improving QOL. Copyright © 2011 John Wiley & Sons, Ltd.

  2. Androgen Deprivation Therapy and maintenance of intimacy: a randomized controlled pilot study of an educational intervention for patients and their partners.

    Science.gov (United States)

    Walker, Lauren M; Hampton, Amy J; Wassersug, Richard J; Thomas, Bejoy C; Robinson, John W

    2013-03-01

    Androgen Deprivation Therapy (ADT) for prostate cancer is associated with many treatment side effects that tend to erode couples' intimacy. We piloted a randomized controlled trial to investigate the effect of an educational intervention designed to preserve couples' intimacy in the face of ADT. Couples were recruited at the time the patient was first prescribed ADT and were randomized to a treatment or control group. Those in the treatment group were asked to read an educational guide and participate in an educational session designed to inform couples about possible ADT side effects and management strategies. To assess changes in the couples' relationships, they were administered the Dyadic Adjustment Scale and the Personal Assessment of Intimacy in Relationships questionnaire prior to randomization and again at 6 months. While results were not statistically significant, trends and effect sizes suggest that the educational intervention helped attenuate declines in intimacy for patients, but not for their partners. Couples who participated in the intervention were more successful at maintaining sexual activity than were couples in the control group. ADT places considerable strain on intimate relationships, particularly for the partners. It appears that patients who receive help in anticipating and managing ADT related changes report better dyadic adjustment and closer intimacy. More efforts are needed to develop interventions to benefit patients' partners. We conclude that the intervention holds promise and that a full-scale evaluation of the intervention is both feasible and warranted. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Additional androgen deprivation makes the difference. Biochemical recurrence-free survival in prostate cancer patients after HDR brachytherapy and external beam radiotherapy

    International Nuclear Information System (INIS)

    Schiffmann, Jonas; Tennstedt, Pierre; Beyer, Burkhard; Boehm, Katharina; Tilki, Derya; Salomon, Georg; Graefen, Markus; Lesmana, Hans; Platz, Volker; Petersen, Cordula; Kruell, Andreas; Schwarz, Rudolf

    2015-01-01

    The role of additional androgen deprivation therapy (ADT) in prostate cancer (PCa) patients treated with combined HDR brachytherapy (HDR-BT) and external beam radiotherapy (EBRT) is still unknown. Consecutive PCa patients classified as D'Amico intermediate and high-risk who underwent HDR-BT and EBRT treatment ± ADT at our institution between January 1999 and February 2009 were assessed. Multivariable Cox regression models predicting biochemical recurrence (BCR) were performed. BCR-free survival was assessed with Kaplan-Meier analyses. Overall, 392 patients were assessable. Of these, 221 (56.4 %) underwent trimodality (HDR-BT and EBRT and ADT) and 171 (43.6 %) bimodality (HDR-BT and EBRT) treatment. Additional ADT administration reduced the risk of BCR (HR: 0.4, 95 % CI: 0.3-0.7, p < 0.001). D'Amico high-risk patients had superior BCR-free survival when additional ADT was administered (log-rank p < 0.001). No significant difference for BCR-free survival was recorded when additional ADT was administered to D'Amico intermediate-risk patients (log-rank p = 0.2). Additional ADT administration improves biochemical control in D'Amico high-risk patients when HDR-BT and EBRT are combined. Physicians should consider the oncological benefit of ADT administration for these patients during the decision-making process. (orig.) [de

  4. Prostate cancer: assessing the effects of androgen-deprivation therapy using quantitative diffusion-weighted and dynamic contrast-enhanced MRI

    Energy Technology Data Exchange (ETDEWEB)

    Hoetker, Andreas M. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Universitaetsmedizin Mainz, Department of Diagnostic and Interventional Radiology, Mainz (Germany); Mazaheri, Yousef [Memorial Sloan-Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Zheng, Junting; Moskowitz, Chaya S. [Memorial Sloan-Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Berkowitz, Joshua; Pei, Xin; Zelefsky, Michael J. [Memorial Sloan-Kettering Cancer Center, Department of Radiation Oncology, New York, NY (United States); Lantos, Joshua E.; Hricak, Hedvig; Akin, Oguz [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States)

    2015-09-15

    To investigate the effects of androgen-deprivation therapy (ADT) on MRI parameters and evaluate their associations with treatment response measures. The study included 30 men with histopathologically confirmed prostate cancer who underwent MRI before and after initiation of ADT. Thirty-four tumours were volumetrically assessed on DW-MRI (n = 32) and DCE-MRI (n = 18), along with regions of interest in benign prostatic tissue, to calculate apparent diffusion coefficient (ADC) and transfer constant (K{sup trans}) values. Changes in MRI parameters and correlations with clinical parameters (change in prostate-specific antigen [PSA], treatment duration, PSA nadir) were assessed. Prostate volume and PSA values decreased significantly with therapy (p < 0.001). ADC values increased significantly in tumours and decreased in benign prostatic tissue (p < 0.05). Relative changes in ADC and absolute post-therapeutic ADC values differed significantly between tumour and benign tissue (p < 0.001). K{sup trans} decreased significantly only in tumours (p < 0.001); relative K{sup trans} changes and post-therapeutic values were not significantly different between tumour and benign tissue. The relative change in tumour ADC correlated significantly with PSA decrease. No changes were associated with treatment duration or PSA nadir. Multi-parametric MRI shows significant measurable changes in tumour and benign prostate caused by ADT and may help in monitoring treatment response. (orig.)

  5. Androgen deprivation decreases prostate specific antigen in the absence of tumor: implications for interpretation of PSA results.

    Science.gov (United States)

    Wenisch, Judith M; Mayr, Florian B; Spiel, Alexander O; Radicioni, Milko; Jilma, Bernd; Jilma-Stohlawetz, Petra

    2014-03-01

    Prostate-specific antigen (PSA) is used as an outcome measure for relapsed disease in prostate cancer. Nonetheless, there are considerable concerns about its indiscriminate use as a surrogate endpoint for cell growth or survival. We hypothesized that treatment with a luteinizing hormone releasing hormone (LHRH) analog would decrease PSA levels even in the absence of malignant disease. We determined testosterone and PSA levels in 30 healthy volunteers after a single intramuscular injection of a LHRH depot formulation. Testosterone and PSA levels were quantified by radioimmunoassay and electrochemi-luminescence immunoassay, respectively. After an initial flare-up during the first 3 days testosterone decreased reaching castration levels in 18 of the 30 young men (60%). After the nadir on day 28, testosterone levels increased to normal again. Changes in PSA paralleled those of testosterone. Castration reduced PSA levels by 29% (95% CI 19%-39%) compared to baseline (pPSA levels by testosterone deprivation. Conferring these findings to tumor patients, decreases in PSA after treatment with LHRH analogs might not only reflect disease regression but also a direct testosterone mediated effect on PSA. Thus, PSA levels should be cautiously interpreted when patients receive hormonal therapy.

  6. Additional androgen deprivation makes the difference. Biochemical recurrence-free survival in prostate cancer patients after HDR brachytherapy and external beam radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Schiffmann, Jonas; Tennstedt, Pierre; Beyer, Burkhard; Boehm, Katharina; Tilki, Derya; Salomon, Georg; Graefen, Markus [University Medical Center Hamburg-Eppendorf, Martini-Clinic Prostate Cancer Center, Hamburg (Germany); Lesmana, Hans; Platz, Volker; Petersen, Cordula; Kruell, Andreas; Schwarz, Rudolf [University Medical Center Hamburg-Eppendorf, Department of Radiation oncology, Hamburg (Germany)

    2015-04-01

    The role of additional androgen deprivation therapy (ADT) in prostate cancer (PCa) patients treated with combined HDR brachytherapy (HDR-BT) and external beam radiotherapy (EBRT) is still unknown. Consecutive PCa patients classified as D'Amico intermediate and high-risk who underwent HDR-BT and EBRT treatment ± ADT at our institution between January 1999 and February 2009 were assessed. Multivariable Cox regression models predicting biochemical recurrence (BCR) were performed. BCR-free survival was assessed with Kaplan-Meier analyses. Overall, 392 patients were assessable. Of these, 221 (56.4 %) underwent trimodality (HDR-BT and EBRT and ADT) and 171 (43.6 %) bimodality (HDR-BT and EBRT) treatment. Additional ADT administration reduced the risk of BCR (HR: 0.4, 95 % CI: 0.3-0.7, p < 0.001). D'Amico high-risk patients had superior BCR-free survival when additional ADT was administered (log-rank p < 0.001). No significant difference for BCR-free survival was recorded when additional ADT was administered to D'Amico intermediate-risk patients (log-rank p = 0.2). Additional ADT administration improves biochemical control in D'Amico high-risk patients when HDR-BT and EBRT are combined. Physicians should consider the oncological benefit of ADT administration for these patients during the decision-making process. (orig.) [German] Der Nutzen einer zusaetzlichen Hormonentzugstherapie (ADT, ''androgen deprivation therapy'') fuer Patienten mit Prostatakarzinom (PCa), welche mit einer Kombination aus HDR-Brachytherapie (HDR-BT) und perkutaner Bestrahlung (EBRT) behandelt werden, ist weiterhin ungeklaert. Fuer diese Studie wurden konsekutive, nach der D'Amico-Risikoklassifizierung in ''intermediate'' und ''high-risk'' eingeteilte Patienten ausgewaehlt, die zwischen Januar 1999 und Februar 2009 in unserem Institut eine kombinierte Therapie aus HDR-BT, EBRT ± ADT erhalten haben. Eine

  7. Long-term outcomes from dose-escalated image-guided intensity-modulated radiotherapy with androgen deprivation: encouraging results for intermediate- and high-risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Wilcox SW

    2014-08-01

    Full Text Available Shea W Wilcox,1,4 Noel J Aherne,2,4 Linus C Benjamin,1 Bosco Wu,1 Thomaz de Campos Silva,3 Craig S McLachlan,4 Michael J McKay,3,5 Andrew J Last,1 Thomas P Shakespeare1–4 1North Coast Cancer Institute, Port Macquarie, NSW, Australia; 2North Coast Cancer Institute, Coffs Harbour, NSW, Australia; 3North Coast Cancer Institute, Lismore, NSW, Australia; 4The University of New South Wales, Rural Clinical School, Sydney, NSW, Australia; 5The University of Sydney, Sydney, NSW, Australia Purpose: Dose-escalated (DE radiotherapy in the setting of localized prostate cancer has been shown to improve biochemical disease-free survival (bDFS in several studies. In the same group of patients, androgen deprivation therapy (ADT has been shown to confer a survival benefit when combined with radiotherapy doses of up to 70 Gy; however, there is currently little long-term data on patients who have received high-dose intensity-modulated radiotherapy (IMRT with ADT. We report the long-term outcomes in a large cohort of patients treated with the combination of DE image-guided IMRT (IG-IMRT and ADT. Methods and materials: Patients with localized prostate cancer were identified from a centralized database across an integrated cancer center. All patients received DE IG-IMRT, combined with ADT, and had a minimum follow up of 12 months post-radiotherapy. All relapse and toxicity data were collected prospectively. Actuarial bDFS, metastasis-free survival, prostate cancer-specific survival, and multivariate analyses were calculated using the SPSS v20.0 statistical package. Results: Seven hundred and eighty-two eligible patients were identified with a median follow up of 46 months. Overall, 4.3% of patients relapsed, 2.0% developed distant metastases, and 0.6% died from metastatic prostate cancer. At 5-years, bDFS was 88%, metastasis-free survival was 95%, and prostate cancer-specific survival was 98%. Five-year grade 2 genitourinary and gastrointestinal toxicity was 2

  8. Patterns of Declining Use and the Adverse Effect of Primary Androgen Deprivation on All-cause Mortality in Elderly Men with Prostate Cancer.

    Science.gov (United States)

    Sammon, Jesse D; Abdollah, Firas; Reznor, Gally; Pucheril, Daniel; Choueiri, Toni K; Hu, Jim C; Kim, Simon P; Schmid, Marianne; Sood, Akshay; Sun, Maxine; Kibel, Adam S; Nguyen, Paul L; Menon, Mani; Trinh, Quoc-Dien

    2015-07-01

    Primary androgen deprivation therapy (pADT) is commonly used to treat elderly men diagnosed with localized prostate cancer (CaP), despite the lack of evidence supporting its use. To examine the effect of pADT on mortality and to assess contemporary trends of pADT use in elderly men with CaP. Men older than 65 yr residing in Surveillance, Epidemiology, and End Results (SEER) registry areas diagnosed with localized or locally advanced CaP between 1992 and 2009 and not receiving definitive therapy. Propensity score (PS)-weighted Cox proportional hazards models were used to estimate the effect of pADT use on overall survival among patients receiving pADT. The interaction between comorbidity-adjusted life expectancy (LE) and pADT use was assessed within the Cox and PS-weighted models. Contemporary (2004-2009) trends for pADT use were analyzed by linear regression. The primary cohort included 46 376 men, of whom 17 873 received pADT (39%). Patients with >10 yr LE had lower pADT utilization rates than patients with short LE. Between 2004 and 2009, the use of pADT in men with localized CaP decreased by 14% (from 36% to 22%). Relative to observation, pADT was associated with a survival disadvantage, with a hazard ratio for all-cause mortality of 1.37 (95% confidence interval 1.20-1.56). Limitations included biases not accounted for by the PS-weighted model, changes in CaP staging over the study period, the absence of prostate-specific antigen (PSA) data prior to 2004, and the limits of retrospective analysis to demonstrate causality. The use of pADT in elderly men with localized CaP has decreased over time. For men forgoing primary definitive therapy, the use of pADT is not associated with a survival benefit compared to observation, and denies men an opportunity for cure with definitive therapy. The deleterious effect of pADT is most pronounced in men with prolonged LE. In this report, we assessed the effect of primary androgen deprivation (pADT) on prostate cancer

  9. Effect of Whole Pelvic Radiotherapy for Patients With Locally Advanced Prostate Cancer Treated With Radiotherapy and Long-Term Androgen Deprivation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mantini, Giovanna [Department of Radiotherapy, Policlinico Universitario A. Gemelli, Catholic University, Rome (Italy); Tagliaferri, Luca, E-mail: luca.tagliaferri@rm.unicatt.it [Department of Radiotherapy, Policlinico Universitario A. Gemelli, Catholic University, Rome (Italy); Mattiucci, Gian Carlo; Balducci, Mario; Frascino, Vincenzo; Dinapoli, Nicola [Department of Radiotherapy, Policlinico Universitario A. Gemelli, Catholic University, Rome (Italy); Di Gesu, Cinzia; Ippolito, Edy; Morganti, Alessio G. [Department of Radiotherapy, John Paul II Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso (Italy); Cellini, Numa [Department of Radiotherapy, Policlinico Universitario A. Gemelli, Catholic University, Rome (Italy)

    2011-12-01

    Purpose: To evaluate the effect of whole pelvic radiotherapy (WPRT) in prostate cancer patients treated with RT and long-term (>1 year) androgen deprivation therapy (ADT). Methods and materials: Prostate cancer patients with high-risk features (Stage T3-T4 and/or Gleason score {>=}7 and/or prostate-specific antigen level {>=}20 ng/mL) who had undergone RT and long-term ADT were included in the present analysis. Patients with bowel inflammatory disease, colon diverticula, and colon diverticulitis were excluded from WPRT and treated with prostate-only radiotherapy (PORT). Patients were grouped according to nodal risk involvement as assessed by the Roach formula using different cutoff levels (15%, 20%, 25%, and 30%). Biochemical disease-free survival (bDFS) was analyzed in each group according to the RT type (WPRT or PORT). Results: A total of 358 patients treated between 1994 and 2007 were included in the analysis (46.9% with WPRT and 53.1% with PORT). The median duration of ADT was 24 months (range, 12-38). With a median follow-up of 52 months (range, 20-150), the overall 4-year bDFS rate was 90.5%. The 4-year bDFS rate was similar between the patients who had undergone WPRT or PORT (90.4% vs. 90.5%; p = NS). However, in the group of patients with the greatest nodal risk (>30%), a significant bDFS improvement was recorded for the patients who had undergone WPRT (p = .03). No differences were seen in acute toxicity among the patients treated with WPRT or PORT. The late gastrointestinal toxicity was similar in patients treated with PORT or WPRT (p = NS). Conclusions: Our analysis has supported the use of WPRT in association with long-term ADT for patients with high-risk nodal involvement (>30%), although a definitive recommendation should be confirmed by a randomized trial.

  10. Development of a nomogram model predicting current bone scan positivity in patients treated with androgen-deprivation therapy for prostate cancer

    Directory of Open Access Journals (Sweden)

    Michael eKattan

    2014-10-01

    Full Text Available Purpose: To develop a nomogram predictive of current bone scan positivity in patients receiving androgen-deprivation therapy (ADT for advanced prostate cancer; to augment clinical judgment and highlight patients in need of additional imaging investigations.Materials and Methods: A retrospective chart review of bone scan records (conventional 99mTc-scintigraphy of 1,293 patients who received ADT at the Memorial Sloan-Kettering Cancer Center from 2000 to 2011. Multivariable logistic regression analysis was used to identify variables suitable for inclusion in the nomogram. The probability of current bone scan positivity was determined using these variables and the predictive accuracy of the nomogram was quantified by concordance index.Results: In total, 2,681 bone scan records were analyzed and 636 patients had a positive result. Overall, the median pre-scan prostate-specific antigen (PSA level was 2.4 ng/ml; median PSA doubling time (PSADT was 5.8 months. At the time of a positive scan, median PSA level was 8.2 ng/ml; 53% of patients had PSA <10 ng/ml; median PSADT was 4.0 months. Five variables were included in the nomogram: number of previous negative bone scans after initiating ADT, PSA level, Gleason grade sum, and history of radical prostatectomy and radiotherapy. A concordance index value of 0.721 was calculated for the nomogram. This was a retrospective study based on limited data in patients treated in a large cancer centre who underwent conventional 99mTc bone scans, which themselves have inherent limitations. Conclusions: This is the first nomogram to predict current bone scan positivity in ADT-treated prostate cancer patients, providing high predictive accuracy.

  11. Lack of benefit for the addition of androgen deprivation therapy to dose-escalated radiotherapy in the treatment of intermediate- and high-risk prostate cancer.

    LENUS (Irish Health Repository)

    Krauss, Daniel

    2012-02-01

    PURPOSE: Assessment of androgen deprivation therapy (ADT) benefits for prostate cancer treated with dose-escalated radiotherapy (RT). METHODS AND MATERIALS: From 1991 to 2004, 1,044 patients with intermediate- (n = 782) or high-risk (n = 262) prostate cancer were treated with dose-escalated RT at William Beaumont Hospital. Patients received external-beam RT (EBRT) alone, brachytherapy (high or low dose rate), or high dose rate brachytherapy plus pelvic EBRT. Intermediate-risk patients had Gleason score 7, prostate-specific antigen (PSA) 10.0-19.9 ng\\/mL, or Stage T2b-T2c. High-risk patients had Gleason score 8-10, PSA >\\/=20, or Stage T3. Patients were additionally divided specifically by Gleason score, presence of palpable disease, and PSA level to further define subgroups benefitting from ADT. RESULTS: Median follow-up was 5 years; 420 patients received ADT + dose-escalated RT, and 624 received dose-escalated RT alone. For all patients, no advantages in any clinical endpoints at 8 years were associated with ADT administration. No differences in any endpoints were associated with ADT administration based on intermediate- vs. high-risk group or RT modality when analyzed separately. Patients with palpable disease plus Gleason >\\/=8 demonstrated improved clinical failure rates and a trend toward improved survival with ADT. Intermediate-risk patients treated with brachytherapy alone had improved biochemical control when ADT was given. CONCLUSION: Benefits of ADT in the setting of dose-escalated RT remain poorly defined. This question must continue to be addressed in prospective study.

  12. Redefining high-risk prostate cancer based on distant metastases and mortality after high-dose radiotherapy with androgen deprivation therapy.

    Science.gov (United States)

    Tendulkar, Rahul D; Reddy, Chandana A; Stephans, Kevin L; Ciezki, Jay P; Klein, Eric A; Mahadevan, Arul; Kupelian, Patrick A

    2012-03-15

    Modern outcomes of high-dose external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT) for high-risk (HR) prostate cancer are not well described. We identified 585 patients who met HR criteria by 2010 National Comprehensive Cancer Network guidelines, who were treated with EBRT consisting of ≥74 Gy from 1996 to 2008 at Cleveland Clinic, of whom 95% received ADT. We analyzed biochemical relapse-free survival (bRFS), distant metastases-free survival (DMFS), and prostate cancer-specific mortality (PCSM). The median EBRT dose was 78 Gy, and median ADT duration was 6 months. At 10 years, the bRFS was 50.2%, the DMFS was 71.6%, and the PCSM was 14.4%. On multivariate analysis, significant predictors of bRFS were biopsy Gleason score (bGS) of 8 to 10, stage T3, and prostate-specific antigen (PSA) concentration; predictors of DMFS were bGS of 8 to 10 and stage T3; the only predictor of PCSM was bGS of 8 to 10. The duration of ADT was not predictive of any endpoint. We identified an unfavorable high-risk (UHR) group of stage T1-T2 tumors consisting of bGS of 8 with PSA of >10 ng/ml or bGS of 9 to 10 with any PSA level; the remaining clinically localized cancers comprised the favorable high-risk (FHR) group. Comparing FHR, UHR, and stage T3 groups, the DMFS rates were 81.4%, 57.8%, and 59.1% (p bGS of 8 to 10 is the strongest predictor of bRFS, DMFS, and PCSM after high-dose EBRT with ADT. The duration of ADT did not correlate with outcome. Future studies should account for the heterogeneity in HR prostate cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Uth, Jacob; Brasso, Klaus; Rørth, Mikael; Krustrup, Peter; Midtgaard, Julie; Schmidt, Jakob Friis; Christensen, Jesper Frank; Hornstrup, Therese; Andersen, Lars Juel; Hansen, Peter Riis; Christensen, Karl Bang; Andersen, Lars Louis; Helge, Eva Wulff

    2013-01-01

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

  14. Statin Use at the Time of Initiation of Androgen Deprivation Therapy and Time to Progression in Patients With Hormone-Sensitive Prostate Cancer.

    Science.gov (United States)

    Harshman, Lauren C; Wang, Xiaodong; Nakabayashi, Mari; Xie, Wanling; Valenca, Loana; Werner, Lillian; Yu, Yongjiang; Kantoff, Aaron M; Sweeney, Christopher J; Mucci, Lorelei A; Pomerantz, Mark; Lee, Gwo-Shu Mary; Kantoff, Philip W

    2015-07-01

    Statin use has been associated with improved prostate cancer outcomes. Dehydroepiandrosterone sulfate (DHEAS) is a precursor of testosterone and a substrate for SLCO2B1, an organic anionic transporter. We previously demonstrated that genetic variants of SLCO2B1 correlated with time to progression (TTP) during receipt of androgen deprivation therapy (ADT). Statins also use SLCO2B1 to enter cells, and thus we hypothesized that they may compete with DHEAS uptake by the tumor cells. To evaluate whether statin use prolongs TTP during ADT for hormone-sensitive prostate cancer. In vitro studies were performed using prostate cancer cell lines at an academic, comprehensive cancer center. Statin use was retrospectively analyzed in 926 patients who had received ADT for biochemical or metastatic recurrence or de novo metastatic prostate cancer between January 1996 and November 2013. To determine whether statins interfere with DHEAS uptake, we performed in vitro studies using prostate cancer cell lines. Next, we queried our institutional clinical database to assess for an association between statin use and TTP during ADT using multivariable Cox regression analysis and adjusted for known prognostic factors. In vitro, we demonstrated that statins block DHEAS uptake by competitively binding to SLCO2B1. In our ADT cohort of 926 patients, 283 (31%) were taking a statin at ADT initiation. After a median follow-up of 5.8 years, 644 patients (70%) had experienced disease progression while receiving ADT. Median TTP during ADT was 20.3 months (95% CI, 18-24 months). Men taking statins had a longer median TTP during ADT compared with nonusers (27.5 [95% CI, 21.1-37.7] vs 17.4 [95% CI, 14.9-21.1] months; P mechanism to support the clinical observation of prolonged TTP in statin users.

  15. The role of androgen deprivation therapy on biochemical failure and distant metastasis in intermediate-risk prostate cancer: effects of radiation dose escalation.

    Science.gov (United States)

    Ludwig, Michelle S; Kuban, Deborah A; Strom, Sara S; Du, Xianglin L; Lopez, David S; Yamal, Jose-Miguel

    2015-03-27

    To determine whether the effect of androgen deprivation therapy (ADT) on the risk of biochemical failure varies at different doses of radiation in patients treated with definitive external beam radiation for intermediate risk prostate cancer (IRPC). This study included 1218 IRPC patients treated with definitive external beam radiation therapy to the prostate and seminal vesicles from June 1987 to January 2009 at our institution. Patient, treatment, and tumor information was collected, including age, race, Gleason score, radiation dose, PSA, T-stage, and months on ADT. The median follow-up was 6 years. A total of 421(34.6%) patients received ADT, 211 (17.3%) patients experienced a biochemical failure, and 38 (3.1%) developed distant metastasis. On univariable analyses, higher PSA, earlier year of diagnosis, higher T-stage, lower doses of radiation, and the lack of ADT were associated with an increased risk of biochemical failure. No difference in biochemical failure was seen among different racial groups or with the use of greater than 6 months of ADT compared with less than 6 months. On multivariate analysis, the use of ADT was associated with a lower risk of biochemical failure than no ADT (HR, 0.599; 95% CI, 0.367-0.978; P<0.04) and lower risk of distant metastasis (HR, 0.114; 95% CI, 0.014-0.905; P=0.04). ADT reduced the risk of biochemical failure and distant metastasis in both low- and high dose radiation groups among men with intermediate-risk PCa. Increasing the duration of ADT beyond 6 months did not reduce the risk of biochemical failures. Better understanding the benefit of ADT in the era of dose escalation will require a randomized clinical trial.

  16. Can androgen-deprivation therapy obviate the need of channel transurethral resection of the prostate in advanced prostate cancer with urinary retention? A prospective study

    Directory of Open Access Journals (Sweden)

    Rajeev Sood

    2017-12-01

    Full Text Available Objective: To evaluate the efficacy of androgen-deprivation therapy (ADT in relieving urinary retention in patients with advanced prostate cancer presenting with urinary retention or a high post-void residual urine volume (PVR. Patients and methods: Patients with advanced prostate cancer with an indwelling catheter for acute/chronic urinary retention, or with a high PVR (>200 mL who had not received any previous treatment were included in the study. Patients with localised prostate cancer eligible for receiving any therapy aimed at cure were excluded. All enrolled patients were managed by ADT (LHRH antagonist/agonist or orchidectomy combined with α-adrenoceptor antagonist/combined therapy for at least 1 month to a maximum of 3 months; they were given their first trial of voiding without catheter after 1 month, and monthly thereafter. Results: A total of 101 patients received ADT of which 97 were able to void successfully at the end of 3 months. In all, 27 patients could void in the first month, followed by 50 in the second month, and an additional 20 in the third month. There was a significant decrease in prostate volume, PVR, and International Prostate Symptom Score, and maximum urinary flow rates improved with normalisation of renal functions and resolution of upper tract changes noted on ultrasonography. Conclusion: ADT can relieve retention and decrease PVR over a period of time obviating the need for channel transurethral resection of the prostate. Keywords: ADT, ADT in retention, Prostate cancer

  17. The perspective of prostate cancer patients and patients' partners on the psychological burden of androgen deprivation and the dyadic adjustment of prostate cancer couples.

    Science.gov (United States)

    Hamilton, Lisa Dawn; Van Dam, Dexter; Wassersug, Richard J

    2016-07-01

    Prostate cancer and its treatments, particularly androgen deprivation therapy (ADT), affect both patients and partners. This study assessed how prostate cancer treatment type, patient mood, and sexual function related to dyadic adjustment from patient and partner perspectives. Men with prostate cancer (n = 206) and partners of men with prostate cancer (n = 66) completed an online survey assessing the patients' mood (profile of mood states short form), their dyadic adjustment (dyadic adjustment scale), and sexual function (expanded prostate cancer index composite). Analyses of covariance found that men on ADT reported better dyadic adjustment compared with men not on ADT. Erectile dysfunction was high for all patients, but a multivariate analysis of variance found that those on ADT experienced greater bother at loss of sexual function than patients not on ADT, suggesting that loss of libido when on ADT does not mitigate the psychological distress associated with loss of erections. In a multiple linear regression, patients' mood predicted their dyadic adjustment, such that worse mood was related to worse dyadic adjustment. However, more bother with patients' overall sexual function predicted lower relationship scores for the patients, while the patients' lack of sexual desire predicted lower dyadic adjustment for partners. Both patients and partners are impacted by the prostate cancer treatment effects on patients' psychological and sexual function. Our data help clarify the way that prostate cancer treatments can affect relationships and that loss of libido on ADT does not attenuate distress about erectile dysfunction. Understanding these changes may help patients and partners maintain a co-supportive relationship. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Effects of a Group-Mediated Exercise and Dietary Intervention in the Treatment of Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: Results From the IDEA-P Trial.

    Science.gov (United States)

    Focht, Brian C; Lucas, Alexander R; Grainger, Elizabeth; Simpson, Christina; Fairman, Ciaran M; Thomas-Ahner, Jennifer M; Buell, Jackie; Monk, J Paul; Mortazavi, Amir; Clinton, Steven K

    2018-04-19

    Although androgen-deprivation therapy (ADT) is the foundation of treatment for prostate cancer, the physiological impacts of ADT result in functional decline and enhanced risk of chronic disease and metabolic syndrome. The Individualized Diet and Exercise Adherence Pilot Trial (IDEA-P) is a single-blind, randomized, pilot trial comparing the effects of a group-mediated, cognitive-behavioral (GMCB) exercise and dietary intervention (EX+D) with those of a standard-of-care (SC) control during the treatment of prostate cancer patients undergoing ADT. A total of 32 prostate cancer patients (M age = 66.28, SD = 7.79) undergoing ADT were randomly assigned to the 12-week EX+D intervention (n = 16) or control (n = 16). The primary outcome in IDEA-P was change in mobility performance with secondary outcomes including body composition and muscular strength. Blinded assessment of outcomes were obtained at baseline and at 2- and 3-month follow-ups. Favorable adherence and retention rates were observed, and no serious intervention-related adverse events were documented. Intent-to-treat ANCOVA controlling for baseline value and ADT duration demonstrated that EX+D resulted in significantly greater improvements in mobility performance (p < .02), muscular strength (p < .01), body fat percentage (p < .05), and fat mass (p < .03) at 3-month follow-up, relative to control. Findings from the IDEA-P trial suggest that a GMCB-based EX+D intervention resulted in significant, clinically meaningful improvements in mobility performance, muscular strength, and body composition, relative to controls. Collectively, these results suggest that the EX+D was a safe and well-tolerated intervention for prostate cancer patients on ADT. The utility of implementing this approach in the treatment of prostate cancer patients on ADT should be evaluated in future large-scale efficacy trials. NCT02050906.

  19. Large institutional variations in use of androgen deprivation therapy with definitive radiotherapy in a population-based cohort of men with intermediate- and high-risk prostate cancer.

    Science.gov (United States)

    Ong, Wee Loon; Foroudi, Farshad; Evans, Sue; Millar, Jeremy

    2017-11-01

    To evaluate the pattern of use of androgen deprivation therapy (ADT) with definitive radiotherapy (RT) in men with prostate cancer (PCa) in a population-based study in Australia. This is a prospective cohort of men with intermediate- and high-risk PCa, captured in the population-based Prostate Cancer Outcome Registry Victoria, who were treated with definitive prostate RT between January 2010 and December 2015. The primary outcome of interest was ADT utilization. Chi-squared test for trend was used to evaluate the temporal trend in the use of ADT over the study period. Multivariate logistic regressions were used to evaluate the effects of patient-, tumour- and treatment-related factors, and treatment institutions (public/ private and metropolitan/ regional) on the likelihood of ADT utilization. A total of 1806 men were included in the study, 199 of whom (11%) had favourable National Comprehensive Cancer Network (NCCN) intermediate-risk disease (i.e. only one intermediate-risk feature, primary Gleason grade 3, and use of brachytherapy boost), treatment institution (public and regional) remained independently associated with increased likelihood of ADT utilization. Men with intermediate-risk PCa treated in regional and public institutions were 2.7 times (95% confidence interval [CI] 1.9-3.9; P use of ADT with definitive prostate RT. While there was an increasing trend towards use of ADT over time, ADT still appeared to be underutilized in certain groups of patients who may benefit from ADT, with approximately one in five men with high-risk and one in two with unfavourable intermediate-risk PCa not receiving ADT with RT. There was notable variation in the use of ADT between public vs private and metropolitan vs regional institutions. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  20. End-of-radiation PSA as a novel prognostic factor in patients undergoing definitive radiation and androgen deprivation therapy for prostate cancer.

    Science.gov (United States)

    Narang, A K; Trieu, J; Radwan, N; Ram, A; Robertson, S P; He, P; Gergis, C; Griffith, E; Singh, H; DeWeese, T A; Honig, S; Annadanam, A; Greco, S; DeVille, C; McNutt, T; DeWeese, T L; Song, D Y; Tran, P T

    2017-06-01

    In men undergoing definitive radiation for prostate cancer, it is unclear whether early biochemical response can provide additional prognostic value beyond pre-treatment risk stratification. Prostate cancer patients consecutively treated with definitive radiation at our institution by a single provider from 1993 to 2006 and who had an end-of-radiation (EOR) PSA (n=688, median follow-up 11.2 years). We analyzed the association of an EOR PSA level, obtained during the last week of radiation, with survival outcomes. Multivariable-adjusted cox proportional hazards models were constructed to assess associations between a detectable EOR PSA (defined as ⩾0.1 ng ml -1 ) and biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS) and overall survival (OS). Kaplan-Meier survival curves were constructed, with stratification by EOR PSA. At the end of radiation, the PSA level was undetectable in 30% of patients. Men with a detectable EOR PSA experienced inferior 10-year BFFS (49.7% versus 64.4%, PPSA. Among National Comprehensive Care Network (NCCN) intermediate- and high-risk men who were treated with definitive radiation and androgen deprivation therapy (ADT), a detectable EOR PSA was more strongly associated with PCSS than initial NCCN risk level (EOR PSA: HR 5.89, 95% CI 2.37-14.65, PPSA was significantly associated with survival endpoints in men who received treatment with definitive radiation and ADT. Whether the EOR PSA can be used to modulate treatment intensity merits further investigation.

  1. The role of androgen deprivation therapy on biochemical failure and distant metastasis in intermediate-risk prostate cancer: effects of radiation dose escalation

    International Nuclear Information System (INIS)

    Ludwig, Michelle S; Kuban, Deborah A; Du, Xianglin L; Lopez, David S; Yamal, Jose-Miguel; Strom, Sara S

    2015-01-01

    To determine whether the effect of androgen deprivation therapy (ADT) on the risk of biochemical failure varies at different doses of radiation in patients treated with definitive external beam radiation for intermediate risk prostate cancer (IRPC). This study included 1218 IRPC patients treated with definitive external beam radiation therapy to the prostate and seminal vesicles from June 1987 to January 2009 at our institution. Patient, treatment, and tumor information was collected, including age, race, Gleason score, radiation dose, PSA, T-stage, and months on ADT. The median follow-up was 6 years. A total of 421(34.6%) patients received ADT, 211 (17.3%) patients experienced a biochemical failure, and 38 (3.1%) developed distant metastasis. On univariable analyses, higher PSA, earlier year of diagnosis, higher T-stage, lower doses of radiation, and the lack of ADT were associated with an increased risk of biochemical failure. No difference in biochemical failure was seen among different racial groups or with the use of greater than 6 months of ADT compared with less than 6 months. On multivariate analysis, the use of ADT was associated with a lower risk of biochemical failure than no ADT (HR, 0.599; 95% CI, 0.367-0.978; P < 0.04) and lower risk of distant metastasis (HR, 0.114; 95% CI, 0.014-0.905; P = 0.04). ADT reduced the risk of biochemical failure and distant metastasis in both low- and high dose radiation groups among men with intermediate-risk PCa. Increasing the duration of ADT beyond 6 months did not reduce the risk of biochemical failures. Better understanding the benefit of ADT in the era of dose escalation will require a randomized clinical trial

  2. Admissions to hospital due to fracture in England in patients with prostate cancer treated with androgen-deprivation therapy - do we have to worry about the hormones?

    Science.gov (United States)

    Jefferies, Edward R; Bahl, Amit; Hounsome, Luke; Eylert, Maike F; Verne, Julia; Persad, Raj A

    2016-09-01

    To investigate the association between androgen-deprivation therapy (ADT) and fracture risk in men with prostate cancer in England. Using the Hospital Episodes Statistics database, which contains all the information about National Health Service (NHS) and NHS-funded hospital admissions in England, for the years 2004-2008, 8 902 patients were found to have had prostate cancer and an admission to hospital with a fracture. Of these patients, 3 372 (37.8%) were identified as being treated with ADT, whilst 5 530 (62.2%) were not. There was a total of 228 852 admissions in the background population. The risk of a fracture requiring hospitalisation increased from 1.12 to 1.41 per 100 person-years in a man with prostate cancer treated with ADT compared with those without ADT, an absolute increase of only 0.29 per 100 person-years. When compared with the background population, there was an increase from 0.58 to 1.41 per 100 person-years, a relative rate ratio increase of 2.4 (P < 0.01) with an absolute increase of 0.83 per 100 person-years. In England there was a small but statistically significant increased risk of fracture in men who had been treated with ADT. Men with prostate cancer, with or without ADT, were at an increased risk of fracture compared with the background population. We therefore suggest that if bone health is to be taken seriously in men with prostate cancer that all these men should be risk assessed (FRAX(®) or Qfracture(®) tools, as National Institute for Health and Care Excellence advised), as all men with prostate cancer have an increased risk of fracture, with those on ADT having slightly higher risk. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

  3. Lack of Apparent Survival Benefit With Use of Androgen Deprivation Therapy in Patients With High-risk Prostate Cancer Receiving Combined External Beam Radiation Therapy and Brachytherapy.

    Science.gov (United States)

    Yang, David D; Muralidhar, Vinayak; Mahal, Brandon A; Nguyen, Paul L; Devlin, Phillip M; King, Martin T; Orio, Peter F

    2018-01-01

    Although level 1 evidence has demonstrated a survival benefit from the addition of androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) for patients with high-risk prostate cancer, the benefits of ADT with combined EBRT and brachytherapy for high-risk patients are unclear. We examined the association between ADT and overall survival in a national cohort of high-risk patients treated with EBRT with or without brachytherapy. We identified 46,325 men in the National Cancer Database with a diagnosis of high-risk prostate cancer (Gleason score 8-10, clinical stage T3-T4, or prostate-specific antigen >20 ng/mL) who were treated with EBRT with or without brachytherapy and ADT from 2004 through 2011. Multivariable Cox regression analysis adjusting for sociodemographic and clinicopathologic factors was used to identify the association between ADT and overall survival. The median follow-up period was 48.6 and 59.2 months for patients treated with EBRT only and combined modality RT, respectively. ADT was associated with an improvement in overall survival for the 85.0% (39,361) of the study cohort who underwent EBRT alone (adjusted hazard ratio 0.91, P=.001) but not for patients treated with combined modality RT (adjusted hazard ratio 1.05, P=.496), with a significant interaction (P interaction =.036). In contrast to the known survival benefit when ADT is given with EBRT, our results suggest that ADT might not improve survival for high-risk patients who undergo combined EBRT and brachytherapy. Given the significant adverse effects of ADT, in particular, with long-term therapy, a randomized controlled trial of combined EBRT and brachytherapy with or without ADT for select high-risk patients using a noninferiority design should be undertaken. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Assessment of mouse cognitive and anxiety-like behaviors and hippocampal inflammation following a repeated and intermittent paradoxical sleep deprivation procedure.

    Science.gov (United States)

    Yin, Mengmei; Chen, Yali; Zheng, Hui; Pu, Tinglin; Marshall, Charles; Wu, Ting; Xiao, Ming

    2017-03-15

    It has been reported that more than one fourth of the world's population suffers from sleep problems. However, there is not a stable and reliable animal model to mimic the persistent and periodic features of sleep disorders, and correspondingly, the feasibility and effectiveness of repeated behavioral tests remains to be determined. In the present study, we repetitively, and intermittently, treated mice with 3days and 7days of paradoxical sleep deprivation (SD), using the modified multiple small-platforms-over-water method for 3 months. The behavioral results suggested that repeated open field and Y-maze tests are able to successfully detect anxiety-like behaviors and working memory dysfunction of the model mice. The Morris water maze test is not suitable for evaluating spatial learning ability following SD because the long-term utilization of the flower-pot method increases the familiarity of mice with the water environment. Moreover, neuroinflammation, microglial activation and neuronal apoptosis were observed in the hippocampus of model mice even recovery for 3 weeks later. This animal model and corresponding behavioral evaluation method will help to explore the pathogenesis and therapeutic strategies of chronic sleep disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Concept and viability of androgen annihilation for advanced prostate cancer.

    Science.gov (United States)

    Mohler, James L

    2014-09-01

    There remains no standard of care for patients with a rising prostate-specific antigen level after radical prostatectomy or radiotherapy but who have no radiographic metastases, even though this is the second largest group of patients with prostate cancer (CaP) in the United States. Androgen deprivation therapy (ADT) may cure some men with advanced CaP based on single-institution series and a randomized clinical trial of immediate versus delayed ADT for men found to have pelvic lymph node metastasis at the time of radical prostatectomy. ADT may be more effective when initiated for minimal disease burden, which can be detected using PSA after radical prostatectomy or radiotherapy, and if more complete disruption of the androgen axis using newer agents decreases the chance that androgen-sensitive cells survive to adapt to a low-androgen environment. Androgens may be "annihilated" simultaneously using a luteinizing hormone-releasing hormone antagonist or agonist to inhibit testicular production of testosterone, a P45017A1 (CYP17A1) inhibitor to diminish metabolism of testosterone via the adrenal pathway and dihydrotestosterone (DHT) via the backdoor pathway, a 5α-reductase (SRD5A) inhibitor to diminish testosterone reduction to DHT and backdoor metabolism of progesterone substrates to DHT, and a newer antiandrogen to compete better with DHT for the androgen receptor ligand-binding domain. Early initiation of androgen annihilation for induction as part of planned intermittent ADT should be safe, may reduce tumor burden below a threshold that allows eradication by the immune system, and may cure many men who have failed definitive local therapy. © 2014 American Cancer Society.

  6. External Beam Radiation Therapy or Brachytherapy With or Without Short-course Neoadjuvant Androgen Deprivation Therapy: Results of a Multicenter, Prospective Study of Quality of Life

    International Nuclear Information System (INIS)

    Gay, Hiram A.; Sanda, Martin G.; Liu, Jingxia; Wu, Ningying; Hamstra, Daniel A.; Wei, John T.; Dunn, Rodney L.; Klein, Eric A.; Sandler, Howard M.; Saigal, Christopher S.; Litwin, Mark S.; Kuban, Deborah A.; Hembroff, Larry; Regan, Meredith M.; Chang, Peter; Michalski, Jeff M.; Regan, Meredith; Hembroff, Larry; Wei, John T.; Hamstra, Dan

    2017-01-01

    Purpose: The long-term effects of neoadjuvant androgen deprivation therapy (NADT) with radiation therapy on participant-reported health-related quality of life (HRQOL) have not been characterized in prospective multicenter studies. We evaluated HRQOL for 2 years among participants undergoing radiation therapy (RT) with or without NADT for newly diagnosed, early-stage prostate cancer. Methods and Materials: We analyzed longitudinal cohort data from the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment Consortium to ascertain the HRQOL trajectory of men receiving NADT with external beam RT (EBRT) or brachytherapy. HRQOL was measured using the expanded prostate cancer index composite 26-item questionnaire at 2, 6, 12, and 24 months after the initiation of NADT. We used the χ 2 or Fisher exact test to compare the shift in percentages between groups that did or did not receive NADT. Analyses were conducted at the 2-sided 5% significance level. Results: For subjects receiving EBRT, questions regarding the ability to have an erection, ability to reach an orgasm, quality of erections, frequency of erections, ability to function sexually, and lack of energy were in a significantly worse dichotomized category for the patients receiving NADT. Comparing the baseline versus 24-month outcomes, 24%, 23%, and 30% of participants receiving EBRT plus NADT shifted to the worse dichotomized category for the ability to reach an orgasm, quality of erections, and ability to function sexually compared with 14%, 13%, and 16% in the EBRT group, respectively. Conclusions: Compared with baseline, at 2 years, participants receiving NADT plus EBRT compared with EBRT alone had worse HRQOL, as measured by the ability to reach orgasm, quality of erections, and ability to function sexually. However, no difference was found in the ability to have an erection, frequency of erections, overall sexual function, hot flashes, breast tenderness/enlargement, depression, lack of

  7. Continued Benefit to Androgen Deprivation Therapy for Prostate Cancer Patients Treated With Dose-Escalated Radiation Therapy Across Multiple Definitions of High-Risk Disease

    International Nuclear Information System (INIS)

    Stenmark, Matthew H.; Blas, Kevin; Halverson, Schuyler; Sandler, Howard M.; Feng, Felix Y.; Hamstra, Daniel A.

    2011-01-01

    Purpose: To analyze prognostic factors in patients with high-risk prostate cancer treated with dose-escalated external-beam radiation therapy (EBRT) and androgen deprivation (ADT). Methods and Materials: Between 1998 and 2008 at University of Michigan Medical Center, 718 men were consecutively treated with EBRT to at least 75 Gy. Seven definitions of high-risk prostate cancer, applying to 11–33% of patients, were evaluated. Biochemical failure (BF), salvage ADT use, metastatic progression, and prostate cancer–specific mortality (PCSM) were estimated by the Kaplan-Meier method and Cox proportional hazards regression. Results: Each high-risk definition was associated with increased BF (hazard ratio [HR] 2.8–3.9, p < 0.0001), salvage ADT use (HR 3.9–6.3, p < 0.0001), metastasis (HR 3.7–6.6, p < 0.0001), and PCSM (HR 3.7–16.2, p < 0.0001). Furthermore, an increasing number of high-risk features predicted worse outcome. Adjuvant ADT yielded significant reductions in both metastases (HR 0.19–0.38, p < 0.001) and PCSM (HR 0.38–0.50, p < 0.05) for all high-risk definitions (with the exception of clinical Stage T3–4 disease) but improved BF only for those with elevated Gleason scores (p < 0.03, HR 0.25–0.48). When treated with ADT and dose-escalated EBRT, patients with Gleason scores 8 to 10, without other high-risk features, had 8-year freedom from BF of 74%, freedom from distant metastases of 93%, and cause-specific survival of 92%, with salvage ADT used in 16% of patients. Conclusion: Adjuvant ADT results in a significant improvement in clinical progression and PCSM across multiple definitions of high-risk disease even with dose-escalated EBRT. There is a subset of patients, characterized by multiple high-risk features or the presence of Gleason Pattern 5, who remain at significant risk for metastasis and PCSM despite current treatment.

  8. Influence of Androgen Deprivation Therapy on All-Cause Mortality in Men With High-Risk Prostate Cancer and a History of Congestive Heart Failure or Myocardial Infarction

    International Nuclear Information System (INIS)

    Nguyen, Paul L.; Chen, Ming-Hui; Beckman, Joshua A.; Beard, Clair J.; Martin, Neil E.; Choueiri, Toni K.; Hu, Jim C.; Hoffman, Karen E.; Dosoretz, Daniel E.; Moran, Brian J.; Salenius, Sharon A.; Braccioforte, Michelle H.; Kantoff, Philip W.; D’Amico, Anthony V.; Ennis, Ronald D.

    2012-01-01

    Purpose: It is unknown whether the excess risk of all-cause mortality (ACM) observed when androgen deprivation therapy (ADT) is added to radiation for men with prostate cancer and a history of congestive heart failure (CHF) or myocardial infarction (MI) also applies to those with high-risk disease. Methods and Materials: Of 14,594 men with cT1c–T3aN0M0 prostate cancer treated with brachytherapy-based radiation from 1991 through 2006, 1,378 (9.4%) with a history of CHF or MI comprised the study cohort. Of these, 22.6% received supplemental external beam radiation, and 42.9% received a median of 4 months of neoadjuvant ADT. Median age was 71.8 years. Median follow-up was 4.3 years. Cox multivariable analysis tested for an association between ADT use and ACM within risk groups, after adjusting for treatment factors, prognostic factors, and propensity score for ADT. Results: ADT was associated with significantly increased ACM (adjusted hazard ratio [AHR] = 1.76; 95% confidence interval [CI], 1.32–2.34; p = 0.0001), with 5-year estimates of 22.71% with ADT and 11.62% without ADT. The impact of ADT on ACM by risk group was as follows: high-risk AHR = 2.57; 95% CI, 1.17–5.67; p = 0.019; intermediate-risk AHR = 1.75; 95% CI, 1.13–2.73; p = 0.012; low-risk AHR = 1.52; 95% CI, 0.96–2.43; p = 0.075). Conclusions: Among patients with a history of CHF or MI treated with brachytherapy-based radiation, ADT was associated with increased all-cause mortality, even for patients with high-risk disease. Although ADT has been shown in Phase III studies to improve overall survival in high-risk disease, the small subgroup of high-risk patients with a history of CHF or MI, who represented about 9% of the patients, may be harmed by ADT.

  9. External Beam Radiation Therapy or Brachytherapy With or Without Short-course Neoadjuvant Androgen Deprivation Therapy: Results of a Multicenter, Prospective Study of Quality of Life

    Energy Technology Data Exchange (ETDEWEB)

    Gay, Hiram A., E-mail: hiramgay@wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Sanda, Martin G. [Department of Urology, Emory University School of Medicine, Atlanta, Georgia (United States); Liu, Jingxia; Wu, Ningying [Division of Public Health Sciences, Washington University School of Medicine, St. Louis, Missouri (United States); Hamstra, Daniel A. [Texas Center for Proton Therapy, Irving, Texas (United States); Wei, John T.; Dunn, Rodney L. [Department of Urology, University of Michigan, Ann Arbor, Michigan (United States); Klein, Eric A. [Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio (United States); Sandler, Howard M. [Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California (United States); Saigal, Christopher S. [Department of Urology, University of California at Los Angeles, Los Angeles, California (United States); Litwin, Mark S. [Department of Urology, University of California at Los Angeles, Los Angeles, California (United States); Health Policy and Management, University of California at Los Angeles, Los Angeles, California (United States); Kuban, Deborah A. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hembroff, Larry [Institute for Public Policy and Social Research, Michigan State University, East Lansing, Michigan (United States); Regan, Meredith M. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Chang, Peter [Department of Surgery, Beth Israel-Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (United States); Michalski, Jeff M. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Regan, Meredith; Hembroff, Larry; Wei, John T.; Hamstra, Dan; and others

    2017-06-01

    Purpose: The long-term effects of neoadjuvant androgen deprivation therapy (NADT) with radiation therapy on participant-reported health-related quality of life (HRQOL) have not been characterized in prospective multicenter studies. We evaluated HRQOL for 2 years among participants undergoing radiation therapy (RT) with or without NADT for newly diagnosed, early-stage prostate cancer. Methods and Materials: We analyzed longitudinal cohort data from the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment Consortium to ascertain the HRQOL trajectory of men receiving NADT with external beam RT (EBRT) or brachytherapy. HRQOL was measured using the expanded prostate cancer index composite 26-item questionnaire at 2, 6, 12, and 24 months after the initiation of NADT. We used the χ{sup 2} or Fisher exact test to compare the shift in percentages between groups that did or did not receive NADT. Analyses were conducted at the 2-sided 5% significance level. Results: For subjects receiving EBRT, questions regarding the ability to have an erection, ability to reach an orgasm, quality of erections, frequency of erections, ability to function sexually, and lack of energy were in a significantly worse dichotomized category for the patients receiving NADT. Comparing the baseline versus 24-month outcomes, 24%, 23%, and 30% of participants receiving EBRT plus NADT shifted to the worse dichotomized category for the ability to reach an orgasm, quality of erections, and ability to function sexually compared with 14%, 13%, and 16% in the EBRT group, respectively. Conclusions: Compared with baseline, at 2 years, participants receiving NADT plus EBRT compared with EBRT alone had worse HRQOL, as measured by the ability to reach orgasm, quality of erections, and ability to function sexually. However, no difference was found in the ability to have an erection, frequency of erections, overall sexual function, hot flashes, breast tenderness/enlargement, depression

  10. Posttreatment Prostate-Specific Antigen 6 Months After Radiation With Androgen Deprivation Therapy Predicts for Distant Metastasis–Free Survival and Prostate Cancer–Specific Mortality

    Energy Technology Data Exchange (ETDEWEB)

    Naik, Mihir, E-mail: naikm@ccf.org [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Reddy, Chandana A.; Stephans, Kevin L.; Ciezki, Jay P. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Garcia, Jorge; Grivas, Petros [Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Stephenson, Andrew J.; Klein, Eric A. [Department of Urology, Glickman Urology and Kidney Institute, Cleveland Clinic, Cleveland, Ohio (United States); Tendulkar, Rahul D. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States)

    2016-11-01

    Objectives/Background: To determine whether a 6-month posttreatment prostate-specific antigen (PSA) value in patients with prostate cancer (PCa) treated with concurrent androgen deprivation therapy (ADT) and external beam radiation therapy (EBRT) serves as an early predictor for biochemical relapse free survival (bRFS), distant metastasis–free survival (DMFS), and prostate cancer–specific mortality (PCSM). Methods: A retrospective review of intermediate-risk and high-risk PCa patients treated with EBRT and concurrent ADT at a single institution between 1996 and 2012. All patients received high-dose radiation with either 78 Gy in 39 fractions or 70 Gy in 28 fractions. Kaplan-Meier analysis was used to estimate bRFS and DMFS, and cumulative incidence was used to estimate PCSM. Results: 532 patients were identified. The median follow-up time was 7.5 years (range, 1-16.25 years). The median initial PSA (iPSA) was 13.0 ng/mL (range, 0.37-255 ng/mL), and the median duration of ADT was 6 months (range, 1-78 months). The median PSA 6 months after EBRT was 0.1 ng/mL (range, 0-19 ng/mL), and 310 patients (58.3%) had a 6-month PSA ≤0.1 ng/mL. Multivariable analysis (MVA) demonstrated that a 6-month post-EBRT PSA of >0.1 ng/mL was an independent predictor of worse bRFS (hazard ratio [HR] = 2.518; P<.0001), DMFS (HR=3.743; P<.0001), and PCSM (HR=5.435; P<.0001). On MVA, a Gleason score of 8 to 10 also correlated with worse DMFS and PCSM (P<.05). The duration of ADT (1-6 vs >6 months) was not predictive of any clinical endpoint. Conclusions: A 6-month posttreatment PSA >0.1 ng/mL in intermediate-risk and high-risk PCa patients treated with concurrent high-dose EBRT and ADT is associated with worse bRFS, DMFS, and PCSM. The duration of ADT was not predictive of any clinical endpoint. A 6-month PSA after definitive EBRT and ADT helps identify patients at higher risk of disease progression and may serve as a predictive tool to select patients for early

  11. High-Dose Radiotherapy With or Without Androgen Deprivation Therapy for Intermediate-Risk Prostate Cancer: Cancer Control and Toxicity Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Edelman, Scott [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA (United States); Liauw, Stanley L. [Department of Radiation Oncology, University of Chicago, Chicago, IL (United States); Rossi, Peter J.; Cooper, Sherrie [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA (United States); Jani, Ashesh B., E-mail: abjani@emory.edu [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA (United States)

    2012-08-01

    Purpose: To evaluate the impact of short-course androgen deprivation therapy (ADT) on cancer control outcomes and toxicity in intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (high-dose radiotherapy [HDRT]). Methods and Materials: Demographic, disease, and treatment characteristics of prostate cancer patients at 2 institution consortiums were charted. Of 296 men with intermediate-risk prostate cancer (defined as {>=}T2b, prostate-specific antigen level >10 ng/mL, or Gleason score [GS] of 7, with none of the following: {>=}T3, prostate-specific antigen level >20 ng/mL, GS {>=}8, or positive nodes) treated with HDRT to a dose of 72 Gy or greater, 123 received short-course ADT and 173 did not. Univariate and multivariate analyses on biochemical failure-free survival (BFFS) (including subset analysis by disease factors) and on overall survival (OS) were performed, as were comparisons of gastrointestinal (GI) and genitourinary (GU) toxicity rates. Results: For the whole group, the median dose was 75.6 Gy; the minimum follow-up was 2 years, and the median follow-up was 47.4 months. For ADT vs. no ADT, the 5-year BFFS rate was 86% vs. 79% (p = 0.138) and the 5-year OS rate was 87% vs. 80% (p = 0.159). On multivariate analysis, percent positive cores (PPC) (p = 0.002) and GS (p = 0.008) were significantly associated with BFFS, with ADT showing a trend (p = 0.055). The impact of ADT was highest in the subsets with PPC greater than 50% (p = 0.019), GS 4+3 (p = 0.078), and number of risk factors greater than 1 (p = 0.022). Only intensity-modulated radiotherapy use (p = 0.012) and GS (p = 0.023) reached significance for OS, and there were no significant differences in GU or GI toxicity. Conclusions: Although the use of ADT with HDRT did not influence BFFS, our study suggests a benefit in patients with PPC greater than 50%, GS 4+3, or multiple risk factors. No OS benefit was shown, and ADT was not associated with additional radiotherapy

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

    Science.gov (United States)

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

    2015-01-01

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

  13. The predictive value of ERG protein expression for development of castration-resistant prostate cancer in hormone-naïve advanced prostate cancer treated with primary androgen deprivation therapy

    DEFF Research Database (Denmark)

    Berg, Kasper Drimer; Røder, Martin A; Thomsen, Frederik B

    2015-01-01

    BACKGROUND: Biomarkers predicting response to primary androgen deprivation therapy (ADT) and risk of castration-resistant prostate cancer (CRPC) is lacking. We aimed to analyse the predictive value of ERG expression for development of CRPC. METHODS: In total, 194 patients with advanced and....../or metastatic prostate cancer (PCa) treated with first-line castration-based ADT were included. ERG protein expression was analysed in diagnostic specimens using immunohistochemistry (anti-ERG, EPR3864). Time to CRPC was compared between ERG subgroups using multiple cause-specific Cox regression stratified...... on ERG-status. Risk reclassification and time-dependent area under the ROC curves were used to assess the discriminative ability of ERG-status. Time to PSA-nadir, proportion achieving PSA-nadir ≤0.2 ng/ml, and risk of PCa-specific death were secondary endpoints. RESULTS: Median follow-up was 6.8 years...

  14. Evaluation of urinary prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG score changes when starting androgen-deprivation therapy with triptorelin 6-month formulation in patients with locally advanced and metastatic prostate cancer

    DEFF Research Database (Denmark)

    Martínez-Piñeiro, Luis; Schalken, Jack A; Cabri, Patrick

    2014-01-01

    OBJECTIVE: To assess prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG scores in patients with advanced and metastatic prostate cancer at baseline and after 6 months of treatment with triptorelin 22.5 mg, and analyse these scores in patient-groups defined by different disease characteristics....... PATIENTS AND METHODS: The Triptocare study was a prospective, open-label, multicentre, single-arm, Phase III study of triptorelin 22.5 mg in men with locally advanced or metastatic prostate cancer, who were naïve to androgen-deprivation therapy (ADT). The primary objective was to model the urinary PCA3...... change at 6 months, according to baseline variables. Other outcome measures included urinary PCA3 and TMPRSS2-ERG scores and statuses, and serum testosterone and prostate-specific antigen (PSA) levels at baseline and at 1, 3 and 6 months after initiation of ADT. Safety was assessed by recording adverse...

  15. Effects of Androgen Blockade on Cognitive Function and Quality of Life in Men with Prostate Cancer

    National Research Council Canada - National Science Library

    Grigsby, James

    2004-01-01

    .... Our major hypothesis is the patients undergoing androgen deprivation therapy will experience impairments in those cognitive abilities reported in the research literature to be related to androgen levels (e.g...

  16. Effects of Androgen Blockade on Cognitive Function and Quality of Life in Men with Prostate Cancer

    National Research Council Canada - National Science Library

    Grigaby, James

    2003-01-01

    .... Our major hypothesis is that patients undergoing androgen deprivation therapy will experience impairments in those cognitive abilities reported in the research literature to be related to androgen levels (e.g...

  17. The prognostic value of expression of HIF1α, EGFR and VEGF-A, in localized prostate cancer for intermediate- and high-risk patients treated with radiation therapy with or without androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Weber Damien C

    2012-04-01

    Full Text Available Abstract Purpose Androgens stimulate the production of hypoxia-inducible factor (HIF1α and ultimately vascular endothelial growth factor (VEGF-A. Additionally, epithelial growth factor (EGF mediates HIF1α production. Carbonic anhydrase IX (CAIX expression is associated with tumor cell hypoxia in a variety of malignancies. This study assesses the prognostic relation between HIF1α, VEGF-A, EGF Receptor and CAIX expression by immunochemistry in diagnostic samples of patients with intermediate- and high-risk localized prostate cancer treated with radiation therapy, with or without androgen deprivation therapy (ADT. Materials and methods Between 1994 and 2004, 103 prostate cancer patients (mean age, 68.7 ± 6.2, with prostate cancer (mean PSA, 13.3 ± 3.7, were treated with radiation therapy (RT, median dose, 74 Gy. Fifty seven (55.3% patients received ADT (median duration, 6 months; range, 0 – 24. Median follow-up was 97.6 months (range, 5.9 – 206.8. Results Higher EGFR expression was significantly (p = 0.04 correlated with higher Gleason scores. On univariate analysis, HIF1α nuclear expression was a significant (p = 0.02 prognostic factor for biological progression-free survival (bPFS. A trend towards significance (p = 0.05 was observed with EGFR expression and bPFS. On multivariate analysis, low HIF1α nuclear (p = 0.01 and high EGFR (p = 0.04 expression remained significant adverse prognostic factors. Conclusions Our study suggests that high nuclear expression of HIF1α and low EGFR expression in diagnostic biopsies of prostate cancer patients treated with RT ± ADT is associated with a good prognosis.

  18. The prognostic value of expression of HIF1α, EGFR and VEGF-A, in localized prostate cancer for intermediate- and high-risk patients treated with radiation therapy with or without androgen deprivation therapy

    International Nuclear Information System (INIS)

    Weber, Damien C; Tille, Jean-Christophe; Combescure, Christophe; Egger, Jean-François; Laouiti, Mahomet; Hammad, Karim; Granger, Perrine; Rubbia-Brandt, Laura; Miralbell, Raymond

    2012-01-01

    Androgens stimulate the production of hypoxia-inducible factor (HIF1α) and ultimately vascular endothelial growth factor (VEGF-A). Additionally, epithelial growth factor (EGF) mediates HIF1α production. Carbonic anhydrase IX (CAIX) expression is associated with tumor cell hypoxia in a variety of malignancies. This study assesses the prognostic relation between HIF1α, VEGF-A, EGF Receptor and CAIX expression by immunochemistry in diagnostic samples of patients with intermediate- and high-risk localized prostate cancer treated with radiation therapy, with or without androgen deprivation therapy (ADT). Between 1994 and 2004, 103 prostate cancer patients (mean age, 68.7 ± 6.2), with prostate cancer (mean PSA, 13.3 ± 3.7), were treated with radiation therapy (RT, median dose, 74 Gy). Fifty seven (55.3%) patients received ADT (median duration, 6 months; range, 0 – 24). Median follow-up was 97.6 months (range, 5.9 – 206.8). Higher EGFR expression was significantly (p = 0.04) correlated with higher Gleason scores. On univariate analysis, HIF1α nuclear expression was a significant (p = 0.02) prognostic factor for biological progression-free survival (bPFS). A trend towards significance (p = 0.05) was observed with EGFR expression and bPFS. On multivariate analysis, low HIF1α nuclear (p = 0.01) and high EGFR (p = 0.04) expression remained significant adverse prognostic factors. Our study suggests that high nuclear expression of HIF1α and low EGFR expression in diagnostic biopsies of prostate cancer patients treated with RT ± ADT is associated with a good prognosis

  19. Prognostic factors in Chinese patients with prostate cancer receiving primary androgen deprivation therapy: validation of Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score and impacts of pre-existing obesity and diabetes mellitus.

    Science.gov (United States)

    Hu, Meng-Bo; Yang, Tian; Hu, Ji-Meng; Zhu, Wen-Hui; Jiang, Hao-Wen; Ding, Qiang

    2018-01-06

    Our aim was to determine the prognostic factors in Chinese patients with prostate cancer receiving primary androgen deprivation therapy (PADT), validate the Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score, and investigate the impacts of pre-existing obesity and diabetes mellitus (DM). The study enrolled Chinese patients diagnosed with prostatic adenocarcinoma and treated with bilateral orchiectomy as PADT at Huashan Hospital, Fudan University (Shanghai, China), from January 2003 to December 2015. The overall survival (OS) and prognostic value of J-CAPRA score, pre-existing obesity, DM, and various clinicopathological variables were analyzed. Of the 435 patients enrolled, 174 (40.0%) deaths occurred during follow-up; 3- and 5-year OS were 74.0 and 58.9%, respectively. Multivariate analysis identified that higher Gleason score and metastasis were both correlated with worse OS and that higher J-CAPRA score was correlated with worse OS [hazard ratio (HR) 1.110, 95% confidence interval (CI) 1.035-1.190, P = 0.003). Different risk categories based on J-CAPRA score showed good stratification in OS (log-rank P = 0.015). In subgroup analysis, pre-existing obesity as a protective factor in younger patients (age ≤ 65, HR 0.271, 95% CI 0.075-0.980, P = 0.046) and pre-existing DM as a risk factor in older patients (> 75, HR 1.854, 95% CI 1.026-3.351, P = 0.041) for OS were recognized, and the prediction accuracy of J-CAPRA was elevated after incorporating pre-existing obesity and DM. The J-CAPRA score presented with good OS differentiation among Chinese patients under PADT. Younger patients (age ≤ 65) had better OS with pre-existing obesity, while older patients (age > 75) had worse OS with pre-existing DM.

  20. A Comparison of the Prognostic Value of Early PSA Test-Based Variables Following External Beam Radiotherapy, With or Without Preceding Androgen Deprivation: Analysis of Data From the TROG 96.01 Randomized Trial

    International Nuclear Information System (INIS)

    Lamb, David S.; Denham, James W.; Joseph, David; Matthews, John; Atkinson, Chris; Spry, Nigel A.; Duchesne, Gillian; Ebert, Martin; Steigler, Allison; Delahunt, Brett; D'Este, Catherine

    2011-01-01

    Purpose: We sought to compare the prognostic value of early prostate-specific antigen (PSA) test-based variables for the 802 eligible patients treated in the Trans-Tasman Radiation Oncology Group 96.01 randomized trial. Methods and Materials: Patients in this trial had T2b, T2c, T3, and T4 N0 prostate cancer and were randomized to 0, 3, or 6 months of neoadjuvant androgen deprivation therapy (NADT) prior to and during radiation treatment at 66 Gy to the prostate and seminal vesicles. The early PSA test-based variables evaluated were the pretreatment initial PSA (iPSA) value, PSA values at 2 and 4 months into NADT, the PSA nadir (nPSA) value after radiation in all patients, and PSA response signatures in men receiving radiation. Comparisons of endpoints were made using Cox models of local progression-free survival, distant failure-free survival, biochemical failure-free survival, and prostate cancer-specific survival. Results: The nPSA value was a powerful predictor of all endpoints regardless of whether NADT was given before radiation. PSA response signatures also predicted all endpoints in men treated by radiation alone. iPSA and PSA results at 2 and 4 months into NADT predicted biochemical failure-free survival but not any of the clinical endpoints. nPSA values correlated with those of iPSA, Gleason grade, and T stage and were significantly higher in men receiving radiation alone than in those receiving NADT. Conclusions: The postradiation nPSA value is the strongest prognostic indicator of all early PSA-based variables. However, its use as a surrogate endpoint needs to take into account its dependence on pretreatment variables and treatment method.

  1. Androgen Deprivation Therapy Use in the Setting of High-dose Radiation Therapy and the Risk of Prostate Cancer–Specific Mortality Stratified by the Extent of Competing Mortality

    Energy Technology Data Exchange (ETDEWEB)

    Rose, Brent S., E-mail: brose44@gmail.com [Harvard Radiation Oncology Program, Brigham and Women' s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Chen, Ming-Hui; Wu, Jing [Department of Statistics, University of Connecticut, Storrs, Connecticut (United States); Braccioforte, Michelle H.; Moran, Brian J. [Prostate Cancer Foundation of Chicago, Westmont, Illinois (United States); Doseretz, Daniel E.; Katin, Michael J.; Ross, Rudolf H.; Salenius, Sharon A. [21st Century Oncology, Inc, Fort Myers, Florida (United States); D' Amico, Anthony V. [Department of Radiation Oncology, Brigham and Women' s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts (United States)

    2016-11-15

    Purpose: The addition of androgen deprivation therapy (ADT) to radiation therapy (RT) is the standard of care for men with intermediate- and high-risk prostate cancer (PC). However, whether competing mortality (CM) affects the ability of ADT to improve, survival remains unanswered. Methods and Materials: We calculated a CM risk score using a Fine-Gray semiparametric model that included age and cardiometabolic comorbidities from a cohort of 17,669 men treated with high-dose RT with or without supplemental ADT for nonmetastatic PC. Fine and Gray competing risk regression analysis was used to assess whether ADT reduced the risk of PC-specific mortality for men with a low versus a high risk of CM among the 4550 patients within the intermediate- and high-risk cohort after adjustment for established PC prognostic factors, year of treatment, site, and ADT propensity score. Results: After a median follow-up of 8.4 years, 1065 men had died, 89 (8.36%) of PC. Among the men with a low CM score, ADT use was associated with a significant reduction in the risk of PC-specific mortality (adjusted hazard ratio 0.35, 95% confidence interval 0.14-0.87, P=.02) but was not for men with high CM (adjusted hazard ratio 1.33, 95% confidence interval 0.77-2.30, P=.30). Conclusions: Adding ADT to high-dose RT appears to be associated with decreased PC-specific mortality risk in men with a low but not a high CM score. These data should serve to heighten awareness about the importance of considering competing risks when determining whether to add ADT to RT for older men with intermediate- or high-risk PC.

  2. Neoadjuvant androgen deprivation and long-term results for patients with intermediate- and high-risk prostate cancer treated with high-dose rate brachytherapy and external beam radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Pellizzon, Antonio Cassio Assis; Fogaroli, Ricardo Cesar; Silva, Maria Leticia Gobo; Castro, Douglas Guedes; Maia, Maria Conte, E-mail: acapellizzon@hcancer.org.b [Hospital A.C. Camargo, Sao Paulo, SP (Brazil). Radiation Oncology Dept.

    2010-07-01

    Purpose: to evaluate the influence of neoadjuvant androgen deprivation (NAAD) and report the long term biochemical control rates according to the Phoenix Consensus Conference, and prognostic factors of intermediate- (IR) and high-risk (HR) prostate cancer treated with external beam radiotherapy and high-dose-rate brachytherapy (HDR-BT). Methods and materials: between March, 1997 and June, 2005, 184 patients considered IR or HR were treated with localized radiotherapy and HDR-BT at the Department of Radiation Oncology, Hospital A.C. Camargo, Sao Paulo, Brazil. Patient's age, Gleason score, clinical stage, initial PSA value, risk group for biochemical failure, presence of NAAD, doses of radiotherapy and HDR-BT were evaluated. Results: median age and follow-up were 70 years old (range, 47-83) and 74.5 months (range, 24-123 months), respectively. Patients considered IR were 91 (49.4%) and HR 93 (50.6%). Ninety-nine (53.8%) patients had no NAAD. The overall survival at 5 years was 93.6%. The 5-year actuarial biochemical control rates for all patients, IR and HR were 83.4%, 86.2% and 78.8%, respectively, p0.076. On univariate analysis the prognostic factors related to better biochemical control were Gleason score < 6 ng/ml (p= 0.037), radiotherapy dose > 45 Gy (p= 0.011) and HDR-BT dose > 20 Gy (p< 0.001). On multivariate analysis no statistical significant predictive factor related to biochemical control was found. Conclusions: the role of NAAD for IR and HR prostate cancer is still to be defined. HDR-BT combined to external radiotherapy is a successful form of treatment for these patients, with our results comparable to published data. (author)

  3. Randomized, Double-Blinded, Placebo-Controlled, Trial of Risedronate for the Prevention of Bone Mineral Density Loss in Nonmetastatic Prostate Cancer Patients Receiving Radiation Therapy Plus Androgen Deprivation Therapy

    International Nuclear Information System (INIS)

    Choo, Richard; Lukka, Himu; Cheung, Patrick; Corbett, Tom; Briones-Urbina, Rosario; Vieth, Reinhold; Ehrlich, Lisa; Kiss, Alex; Danjoux, Cyril

    2013-01-01

    Purpose: Androgen deprivation therapy (ADT) has been used as an adjuvant treatment to radiation therapy (RT) for the management of locally advanced prostate carcinoma. Long-term ADT decreases bone mineral density (BMD) and increases the risk of osteoporosis. The objective of this clinical trial was to evaluate the efficacy of risedronate for the prevention of BMD loss in nonmetastatic prostate cancer patients undergoing RT plus 2 to 3 years of ADT. Methods and Materials: A double-blinded, placebo-controlled, randomized trial was conducted for nonmetastatic prostate cancer patients receiving RT plus 2 to 3 years of ADT. All had T scores > −2.5 on dual energy x-ray absorptiometry at baseline. Patients were randomized 1:1 between risedronate and placebo for 2 years. The primary endpoints were the percent changes in the BMD of the lumbar spine at 1 and 2 years from baseline, measured by dual energy x-ray absorptiometry. Analyses of the changes in BMD and bone turnover biomarkers were carried out by comparing mean values of the intrapatient changes between the 2 arms, using standard t tests. Results: One hundred four patients were accrued between 2004 and 2007, with 52 in each arm. Mean age was 66.8 and 67.5 years for the placebo and risedronate, respectively. At 1 and 2 years, mean (±SE) BMD of the lumbar spine decreased by 5.77% ± 4.66% and 13.55% ± 6.33%, respectively, in the placebo, compared with 0.12% ± 1.29% at 1 year (P=.2485) and 0.85% ± 1.56% (P=.0583) at 2 years in the risedronate. The placebo had a significant increase in serum bone turnover biomarkers compared with the risedronate. Conclusions: Weekly oral risedronate prevented BMD loss at 2 years and resulted in significant suppression of bone turnover biomarkers for 24 months for patients receiving RT plus 2 to 3 years of ADT

  4. Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Felix Y., E-mail: ffeng@med.umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiation Oncology, Veterans Affairs Medical Center, Ann Arbor, Michigan (United States); Blas, Kevin; Olson, Karin; Stenmark, Matthew [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Sandler, Howard [Cedars Sinai Medical Center, Los Angeles, California (United States); Hamstra, Daniel A. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

    2013-05-01

    Purpose: To evaluate the role of androgen deprivation therapy (ADT) and duration for high-risk prostate cancer patients treated with dose-escalated radiation therapy (RT). Methods and Materials: A retrospective analysis of high-risk prostate cancer patients treated with dose-escalated RT (minimum 75 Gy) with or without ADT was performed. The relationship between ADT use and duration with biochemical failure (BF), metastatic failure (MF), prostate cancer-specific mortality (PCSM), non-prostate cancer death (NPCD), and overall survival (OS) was assessed as a function of pretreatment characteristics, comorbid medical illness, and treatment using Fine and Gray's cumulative incidence methodology. Results: The median follow-up time was 64 months. In men with National Comprehensive Cancer Network defined high-risk prostate cancer treated with dose-escalated RT, on univariate analysis, both metastasis (P<.0001; hazard ratio 0.34; 95% confidence interval 0.18-0.67; cumulative incidence at 60 months 13% vs 35%) and PCSM (P=.015; hazard ratio 0.41; 95% confidence interval 0.2-1.0; cumulative incidence at 60 months 6% vs 11%) were improved with the use of ADT. On multivariate analysis for all high-risk patients, Gleason score was the strongest negative prognostic factor, and long-term ADT (LTAD) improved MF (P=.002), PCSM (P=.034), and OS (P=.001). In men with prostate cancer and Gleason scores 8 to 10, on multivariate analysis after adjustment for other risk features, there was a duration-dependent improvement in BF, metastasis, PCSM, and OS, all favoring LTAD in comparison with STAD or RT alone. Conclusion: For men with high-risk prostate cancer treated with dose-escalated EBRT, this retrospective study suggests that the combination of LTAD and RT provided a significant improvement in clinical outcome, which was especially true for those with Gleason scores of 8 to 10.

  5. Nadir prostate-specific antigen (PSA) level and time to PSA nadir following primary androgen deprivation therapy as independent prognostic factors in a Japanese large-scale prospective cohort study (J-CaP).

    Science.gov (United States)

    Kitagawa, Yasuhide; Ueno, Satoru; Izumi, Kouji; Mizokami, Atsushi; Hinotsu, Shiro; Akaza, Hideyuki; Namiki, Mikio

    2014-04-01

    The aim of this study was to investigate whether nadir prostate-specific antigen (PSA) level and time to PSA nadir (TTN) are independent prognostic factors equivalent to the pretreatment factors in the data of the Japan Study Group of Prostate Cancer registry, which is a large, multicenter, population-based database of patients undergoing primary androgen deprivation therapy (PADT). A total of 10,958 patients treated with PADT were enrolled into the present study. Univariate and multivariate Cox proportional hazards regression analysis and Kaplan-Meier analysis were used to evaluate the associations of PSA nadir level and TTN with progression-free survival (PFS) and overall survival (OS), adjusting for the pretreatment factors adopted in the Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score. Of the 10,958 patients, 3,451 (31.5%) had lymph node and/or distant metastases. The median PSA level was 27.0 ng/ml before treatment, and the nadir PSA level in 6,983 patients (63.7%) reached below 0.2 ng/ml. Disease progression occurred in 4,736 cases, and 2,163 patients died during a mean follow-up period of 3.86 years. Nadir PSA level and TTN were independent prognostic factors, similar to the pretreatment factors adopted in the J-CAPRA score. The probabilities of PFS and OS showed significant differences among the groups categorized by the combination of nadir PSA level and TTN in all J-CAPRA risk stratifications. The present study demonstrated that nadir PSA level and TTN are strong predictors in patients undergoing PADT in a large-scale prospective cohort study.

  6. The impact of comorbidity and PSA doubling time on the risk of death in men experiencing PSA failure following radiation therapy with or with androgen deprivation therapy for unfavorable-risk prostate cancer.

    Science.gov (United States)

    Patel, S A; Chen, M-H; Loffredo, M; Renshaw, A; Kantoff, P W; D'Amico, A V

    2017-06-01

    The optimal management of men with PSA failure following initial prostate cancer (PC) therapy stratified by comorbidity is unknown. We investigated the impact that PSA doubling time (DT) and comorbidity had on the risk of all-cause mortality (ACM), prostate cancer-specific mortality (PCSM) and other-cause mortality (OCM) following PSA failure. Between 1995 and 2001, 206 men with unfavorable-risk PC were randomized to receive radiation therapy alone or in combination with 6 months of androgen deprivation therapy (ADT); 108 men experienced PSA failure and formed the study cohort. Cox and Fine-Gray regression analysis was used to determine whether PSA DT was associated with the risk of ACM and PCSM/OCM, respectively, stratified by comorbidity status using a validated metric. After a median follow-up of 13.71 years following PSA failure, 81 of the 108 men (75%) died. Longer PSA DT was associated with a decreased risk of PCSM in men with no/minimal (adjusted hazard ratio (AHR) 0.33, 95% confidence interval (CI) 0.17-0.65, P=0.001) and moderate/severe comorbidity (AHR 0.014, 95% CI 0.002-0.129, P=0.0002). However, because of the different contributions of the risk of OCM to risk of ACM within comorbidity subgroups, increasing PSA DT was only associated with a decreased risk of ACM in men with no/minimal (AHR 0.69, 95% CI 0.50-0.96, P=0.03) but not moderate/severe comorbidity (AHR 0.95, 95% CI 0.51-1.78, P=0.87). Both the extent of comorbidity and the PSA DT should be taken into consideration when deciding on appropriate management and/or clinical trial eligibility at the time of PSA failure.

  7. Randomized, Double-Blinded, Placebo-Controlled, Trial of Risedronate for the Prevention of Bone Mineral Density Loss in Nonmetastatic Prostate Cancer Patients Receiving Radiation Therapy Plus Androgen Deprivation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Choo, Richard [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Lukka, Himu [Department of Radiation Oncology, Juravinski Cancer Center, McMaster University, Hamilton (Canada); Cheung, Patrick [Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto (Canada); Corbett, Tom [Department of Radiation Oncology, Juravinski Cancer Center, McMaster University, Hamilton (Canada); Briones-Urbina, Rosario [Department of Medicine, Women' s College Hospital, University of Toronto, Toronto (Canada); Vieth, Reinhold [Departments of Nutritional Sciences and Laboratory Medicine and Pathology, Mount Sinai Hospital, University of Toronto, Toronto (Canada); Ehrlich, Lisa [Department of Radiology, Sunnybrook Health Sciences Center, University of Toronto (Canada); Kiss, Alex [Department of Health Policy, Management, and Evaluation, Sunnybrook Health Sciences Center, University of Toronto, Toronto (Canada); Danjoux, Cyril, E-mail: Cyril.danjoux@sunnybrook.ca [Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto (Canada)

    2013-04-01

    Purpose: Androgen deprivation therapy (ADT) has been used as an adjuvant treatment to radiation therapy (RT) for the management of locally advanced prostate carcinoma. Long-term ADT decreases bone mineral density (BMD) and increases the risk of osteoporosis. The objective of this clinical trial was to evaluate the efficacy of risedronate for the prevention of BMD loss in nonmetastatic prostate cancer patients undergoing RT plus 2 to 3 years of ADT. Methods and Materials: A double-blinded, placebo-controlled, randomized trial was conducted for nonmetastatic prostate cancer patients receiving RT plus 2 to 3 years of ADT. All had T scores > −2.5 on dual energy x-ray absorptiometry at baseline. Patients were randomized 1:1 between risedronate and placebo for 2 years. The primary endpoints were the percent changes in the BMD of the lumbar spine at 1 and 2 years from baseline, measured by dual energy x-ray absorptiometry. Analyses of the changes in BMD and bone turnover biomarkers were carried out by comparing mean values of the intrapatient changes between the 2 arms, using standard t tests. Results: One hundred four patients were accrued between 2004 and 2007, with 52 in each arm. Mean age was 66.8 and 67.5 years for the placebo and risedronate, respectively. At 1 and 2 years, mean (±SE) BMD of the lumbar spine decreased by 5.77% ± 4.66% and 13.55% ± 6.33%, respectively, in the placebo, compared with 0.12% ± 1.29% at 1 year (P=.2485) and 0.85% ± 1.56% (P=.0583) at 2 years in the risedronate. The placebo had a significant increase in serum bone turnover biomarkers compared with the risedronate. Conclusions: Weekly oral risedronate prevented BMD loss at 2 years and resulted in significant suppression of bone turnover biomarkers for 24 months for patients receiving RT plus 2 to 3 years of ADT.

  8. The Outcome for Patients With Pathologic Node-Positive Prostate Cancer Treated With Intensity Modulated Radiation Therapy and Androgen Deprivation Therapy: A Case-Matched Analysis of pN1 and pN0 Patients

    Energy Technology Data Exchange (ETDEWEB)

    Van Hemelryk, Annelies [Department of Urology, Ghent University Hospital, Ghent (Belgium); De Meerleer, Gert; Ost, Piet [Department of Radiation Oncology, Ghent University Hospital, Ghent (Belgium); Poelaert, Filip [Department of Urology, Ghent University Hospital, Ghent (Belgium); De Gersem, Werner [Department of Radiation Oncology, Ghent University Hospital, Ghent (Belgium); Decaestecker, Karel [Department of Urology, Ghent University Hospital, Ghent (Belgium); De Visschere, Pieter [Department of Radiology, Ghent University Hospital, Ghent (Belgium); Fonteyne, Valérie, E-mail: valerie.fonteyne@uzgent.be [Department of Radiation Oncology, Ghent University Hospital, Ghent (Belgium)

    2016-10-01

    Purpose: Improved outcome is reported after surgery or external beam radiation therapy (EBRT) plus androgen deprivation therapy (ADT) for patients with lymph node (LN) positive (N1) prostate cancer (PC). Surgical series have shown that pathologic (p)N1 PC does not behave the same in all patients. The aim of this study was to perform a matched-case analysis to compare the outcome of pN1 and pN0 PC after high-dose EBRT plus ADT. Methods and Materials: Radiation therapy up to 80 Gy was delivered to the prostate with a minimal dose of 45 Gy to the pelvis for pN1 patients. After matching, Kaplan-Meier statistics were used to compare the 5-year biochemical and clinical relapse-free survival (bRFS and cRFS), prostate cancer–specific survival (PCSS), and overall survival (OS). Acute and late rectal and urinary toxicity was evaluated. Results: Sixty-nine pN1 PC patients were matched 1:1 with pN0 PC patients. The median follow-up time was 60 months. The 5-year bRFS and cRFS for pN1 versus pN0 PC patients were 65% ± 7% versus 79% ± 5% (P=.08) and 70% ± 6% versus 83% ± 5% (P=.04) respectively. No significant difference was found in bRFS or cRFS rates between low volume pN1 (≤2 positive LNs) and pN0 patients. The 5-year PCSS and OS were comparable between pN1 and pN0 PC patients: PCSS: 92% ± 4% versus 93% ± 3% (P=.66); OS: 82% ± 5% versus 80% ± 5% (P=.58). Severe toxicity was rare for both groups, although pN1 patients experienced significantly more acute grade 2 rectal toxicity. Conclusion: Primary EBRT plus 2 to 3 years of ADT is a legitimate treatment option for pN1 PC patients, especially those with ≤2 positive LNs, and this with bRFS and cRFS rates comparable to those in pN0 PC patients. For pN1 PC patients with >2 positive LNs, bRFS and cRFS are worse than in pN0 patients, but even in this subgroup, long-term disease control is obtained.

  9. Late Radiation and Cardiovascular Adverse Effects After Androgen Deprivation and High-Dose Radiation Therapy in Prostate Cancer: Results From the DART 01/05 Randomized Phase 3 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Zapatero, Almudena, E-mail: almudena.zapatero@salud.madrid.org [Hospital Universitario de la Princesa, Madrid (Spain); Guerrero, Araceli [Hospital Son Espases, Palma de Mallorca (Spain); Maldonado, Xavier [Hospital Universitari Vall d' Hebron, Barcelona (Spain); Álvarez, Ana; González-San Segundo, Carmen [Hospital General Universitario Gregorio Marañón, Madrid (Spain); Cabeza Rodriguez, Maria Angeles [Hospital Universitario 12 de Octubre, Madrid (Spain); Macías, Victor [Hospital General de Catalunya, Sant Cugat del Vallès and Hospital Universitario de Salamanca, Salamanca (Spain); Pedro Olive, Agustí [Hospital Plató, Barcelona (Spain); Casas, Francesc [Hospital Clinic, Barcelona (Spain); Boladeras, Ana [Institut Català d' Oncologia, Barcelona (Spain); Martín de Vidales, Carmen [Hospital Universitario de la Princesa, Madrid (Spain); Vázquez de la Torre, Maria Luisa [Hospital Do Meixoeiro, Vigo (Spain); Calvo, Felipe A. [Hospital General Universitario Gregorio Marañón, Madrid (Spain)

    2016-10-01

    Purpose: To present data on the late toxicity endpoints of a randomized trial (DART 01/05) conducted to determine whether long-term androgen deprivation (LTAD) was superior to short-term AD (STAD) when combined with high-dose radiation therapy (HDRT) in patients with prostate cancer (PCa). Patients and Methods: Between November 2005 and December 2010, 355 eligible men with cT1c-T3aN0M0 PCa and intermediate-risk and high-risk factors (2005 National Comprehensive Cancer Network criteria) were randomized to 4 months of AD combined with HDRT (median dose, 78 Gy) (STAD) or the same treatment followed by 24 months of AD (LTAD). Treatment-related complications were assessed using European Organization for Research and Treatment of Cancer–Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events v3.0 scoring schemes. Multivariate analyses for late toxicity were done using the Fine-Gray method. Results: The 5-year incidence of grade ≥2 rectal and urinary toxicity was 11.1% and 8.2% for LTAD and 7.6% and 7.3% for STAD, respectively. Compared with STAD, LTAD was not significantly associated with a higher risk of late grade ≥2 rectal toxicity (hazard ratio [HR] 1.360, 95% confidence interval [CI] 0.660-2.790, P=.410) or urinary toxicity (HR 1.028, 95% CI 0.495-2.130, P=.940). The multivariate analysis showed that a baseline history of intestinal comorbidity (HR 3.510, 95% CI 1.560-7.930, P=.025) and the rectal volume receiving >60 Gy (Vr60) (HR 1.030, 95% CI 1.001-1.060, P=.043) were the only factors significantly correlated with the risk of late grade ≥2 rectal complications. A history of previous surgical prostate manipulations was significantly associated with a higher risk of grade ≥2 urinary complications (HR 2.427, 95% CI 1.051-5.600, P=.038). Long-term AD (HR 2.090; 95% CI 1.170-3.720, P=.012) and a history of myocardial infarction (HR 2.080; 95% CI 1.130-3.810, P=.018) were significantly correlated with a higher probability of

  10. Long-Term Follow-Up of a Prospective Trial of Trimodality Therapy of Weekly Paclitaxel, Radiation, and Androgen Deprivation in High-Risk Prostate Cancer With or Without Prior Prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, Arif, E-mail: ahussain@som.umaryland.edu [University of Maryland Greenebaum Cancer Center, Baltimore, MD (United States); Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (United States); Baltimore VA Medical Center, Baltimore, MD (United States); Wu, Yin [Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (United States); Mirmiran, Alireza [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); DiBiase, Steven [Cooper University Hospital, Camden, NJ (United States); Goloubeva, Olga [University of Maryland Greenebaum Cancer Center, Baltimore, MD (United States); Bridges, Benjamin [University of Maryland Greenebaum Cancer Center, Baltimore, MD (United States); Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (United States); Mannuel, Heather [University of Maryland Greenebaum Cancer Center, Baltimore, MD (United States); Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (United States); Baltimore VA Medical Center, Baltimore, MD (United States); Engstrom, Christine [Baltimore VA Medical Center, Baltimore, MD (United States); Dawson, Nancy [Lombardi Cancer Center, Georgetown University, Washington, D.C (United States); Amin, Pradip; Kwok, Young [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States)

    2012-01-01

    Purpose: Weekly paclitaxel, concurrent radiation, and androgen deprivation (ADT) were evaluated in patients with high-risk prostate cancer (PC) with or without prior prostatectomy (RP). Methods and Materials: Eligible post-RP patients included: pathological T3 disease, or rising prostate-specific antigen (PSA) {>=}0.5 ng/mL post-RP. Eligible locally advanced PC (LAPC) patients included: 1) cT2b-4N0N+, M0; 2) Gleason score (GS) 8-10; 3) GS 7 + PSA 10-20 ng/mL; or 4) PSA 20-150 ng/mL. Treatment included ADT (4 or 24 months), weekly paclitaxel (40, 50, or 60 mg/m{sup 2}/wk), and pelvic radiation therapy (total dose: RP = 64.8 Gy; LAPC = 70.2 Gy). Results: Fifty-nine patients were enrolled (LAPC, n = 29; RP, n = 30; ADT 4 months, n = 29; 24 months, n = 30; whites n = 29, African Americans [AA], n = 28). Baseline characteristics (median [range]) were: age 67 (45-86 years), PSA 5.9 (0.1-92.1 ng/mL), GS 8 (6-9). At escalating doses of paclitaxel, 99%, 98%, and 95% of doses were given with radiation and ADT, respectively, with dose modifications required primarily in RP patients. No acute Grade 4 toxicities occurred. Grade 3 toxicities were diarrhea 15%, urinary urgency/incontinence 10%, tenesmus 5%, and leukopenia 3%. Median follow-up was 75.3 months (95% CI: 66.8-82.3). Biochemical progression occurred in 24 (41%) patients and clinical progression in 11 (19%) patients. The 5- and 7-year OS rates were 83% and 67%. There were no differences in OS between RP and LAPC, 4- and 24-month ADT, white and AA patient categories. Conclusions: In addition to LAPC, to our knowledge, this is the first study to evaluate concurrent chemoradiation with ADT in high-risk RP patients. With a median follow-up of 75.3 months, this trial also represents the longest follow-up of patients treated with taxane-based chemotherapy with EBRT in high-risk prostate cancer. Concurrent ADT, radiation, and weekly paclitaxel at 40 mg/m{sup 2}/week in RP patients and 60 mg/m{sup 2}/week in LAPC patients is

  11. Late Radiation and Cardiovascular Adverse Effects After Androgen Deprivation and High-Dose Radiation Therapy in Prostate Cancer: Results From the DART 01/05 Randomized Phase 3 Trial

    International Nuclear Information System (INIS)

    Zapatero, Almudena; Guerrero, Araceli; Maldonado, Xavier; Álvarez, Ana; González-San Segundo, Carmen; Cabeza Rodriguez, Maria Angeles; Macías, Victor; Pedro Olive, Agustí; Casas, Francesc; Boladeras, Ana; Martín de Vidales, Carmen; Vázquez de la Torre, Maria Luisa; Calvo, Felipe A.

    2016-01-01

    Purpose: To present data on the late toxicity endpoints of a randomized trial (DART 01/05) conducted to determine whether long-term androgen deprivation (LTAD) was superior to short-term AD (STAD) when combined with high-dose radiation therapy (HDRT) in patients with prostate cancer (PCa). Patients and Methods: Between November 2005 and December 2010, 355 eligible men with cT1c-T3aN0M0 PCa and intermediate-risk and high-risk factors (2005 National Comprehensive Cancer Network criteria) were randomized to 4 months of AD combined with HDRT (median dose, 78 Gy) (STAD) or the same treatment followed by 24 months of AD (LTAD). Treatment-related complications were assessed using European Organization for Research and Treatment of Cancer–Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events v3.0 scoring schemes. Multivariate analyses for late toxicity were done using the Fine-Gray method. Results: The 5-year incidence of grade ≥2 rectal and urinary toxicity was 11.1% and 8.2% for LTAD and 7.6% and 7.3% for STAD, respectively. Compared with STAD, LTAD was not significantly associated with a higher risk of late grade ≥2 rectal toxicity (hazard ratio [HR] 1.360, 95% confidence interval [CI] 0.660-2.790, P=.410) or urinary toxicity (HR 1.028, 95% CI 0.495-2.130, P=.940). The multivariate analysis showed that a baseline history of intestinal comorbidity (HR 3.510, 95% CI 1.560-7.930, P=.025) and the rectal volume receiving >60 Gy (Vr60) (HR 1.030, 95% CI 1.001-1.060, P=.043) were the only factors significantly correlated with the risk of late grade ≥2 rectal complications. A history of previous surgical prostate manipulations was significantly associated with a higher risk of grade ≥2 urinary complications (HR 2.427, 95% CI 1.051-5.600, P=.038). Long-term AD (HR 2.090; 95% CI 1.170-3.720, P=.012) and a history of myocardial infarction (HR 2.080; 95% CI 1.130-3.810, P=.018) were significantly correlated with a higher probability of

  12. Transperineal prostate brachytherapy, using I-125 seed with or without adjuvant androgen deprivation, in patients with intermediate-risk prostate cancer: study protocol for a phase III, multicenter, randomized, controlled trial

    Directory of Open Access Journals (Sweden)

    Miyakoda Keiko

    2010-10-01

    Full Text Available Abstract Background The optimal protocol for 125I-transperineal prostatic brachytherapy (TPPB in intermediate-risk prostate cancer (PCa patients remains controversial. Data on the efficacy of combining androgen-deprivation therapy (ADT with 125I-TPPB in this group remain limited and consequently the guidelines of the American Brachytherapy Society (ABS provide no firm recommendations. Methods/Design Seed and Hormone for Intermediate-risk Prostate Cancer (SHIP 0804 is a phase III, multicenter, randomized, controlled study that will investigate the impact of adjuvant ADT following neoadjuvant ADT and 125I-TPPB. Prior to the end of March, 2011, a total of 420 patients with intermediate-risk, localized PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from 20 institutions, all of which have broad experience of 125I-TPPB. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will initially undergo 3-month ADT prior to 125I-TPPB. Those randomly assigned to adjuvant therapy will subsequently undergo 9 months of adjuvant ADT. All participants will be assessed at baseline and at the following intervals: every 3 months for the first 24 months following 125I-TPPB, every 6 months during the 24- to 60-month post-125I-TPPB interval, annually between 60 and 84 months post-125I-TPPB, and on the 10th anniversary of treatment. The primary endpoint is biochemical progression-free survival (BPFS. Secondary endpoints are overall survival (OS, clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, acceptability (assessed using the international prostate symptom score [IPSS], quality of life (QOL evaluation, and adverse events. In the correlative study (SHIP36B, we also evaluate biopsy results at 36 months following treatment to examine the relationship between the results and the eventual recurrence after completion of radiotherapy

  13. Andrographolide Targets Androgen Receptor Pathway in Castration-Resistant Prostate Cancer

    OpenAIRE

    Liu, Chengfei; Nadiminty, Nagalakshmi; Tummala, Ramakumar; Chun, Jae Yeon; Lou, Wei; Zhu, Yezi; Sun, Meng; Evans, Christopher P.; Zhou, Qinghua; Gao, Allen C.

    2011-01-01

    Androgen receptor (AR) signaling not only plays a pivotal role in the development of androgen-dependent prostate cancer but is also important in the growth and survival of castration-resistant prostate cancer (CRPC). The first line of treatment of androgen-dependent prostate cancer is the use of androgen deprivation therapy. However, most patients will eventually relapse due to development of CRPC. Thus, development of a strategy to target AR for treatment of CRPC is urgently needed. The auth...

  14. Efficacy and Safety of Combined Androgen Deprivation Therapy (ADT and Docetaxel Compared with ADT Alone for Metastatic Hormone-Naive Prostate Cancer: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Tobias Engel Ayer Botrel

    Full Text Available Prostate cancer is the most common nonskin cancer and second most common cause of cancer mortality in older men in the United States (USA and Western Europe. Androgen-deprivation therapy alone (ADT remains the first line of treatment in most cases, for metastatic disease. We performed a systematic review and meta-analysis of all randomized controlled trials (RCT that compared the efficacy and adverse events profile of a chemohormonal therapy (ADT ± docetaxel for metastatic hormone-naive prostate cancer (mHNPC.Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoint was overall survival. Data extracted from the studies were combined by using the hazard ratio (HR or risk ratio (RR with their corresponding 95% confidence intervals (95% CI.The final analysis included 3 trials comprising 2,264 patients (mHNPC. Patients who received the chemohormonal therapy had a longer clinical progression-free survival interval (HR = 0.64; 95% CI: 0.55 to 0.75; p<0.00001, and no heterogeneity (Chi2 = 0.64; df = 1 [p = 0.42]; I2 = 0%. The biochemical progression-free survival (bPFS also was higher in patients treated with ADT plus docetaxel (HR = 0.63; 95% CI: 0.57 to 0.69; p<0.00001, also with no heterogeneity noted (Chi2 = 0.48; df = 2 [p = 0.79]; I2 = 0%. Finally, the combination of ADT with docetaxel showed a superior overall survival (OS compared with ADT alone (HR = 0.73; 95% CI: 0.64 to 0.84; p<0.0001, with moderate heterogeneity (Chi2 = 3.84; df = 2 [p = 0.15]; I2 = 48%. A random-effects model analysis was performed, and the results remained favorable to the use of ADT plus docetaxel (HR = 0.73; 95% CI: 0.60 to 0.89; p = 0.002. In the final combined analysis of the high-volume disease patients, the use of the combination therapy also favored an increased overall survival (HR = 0.67; 95% CI: 0.54 to 0.83; p = 0.0003. Regarding adverse events and severe toxicity (grade ≥3, the group receiving the combined therapy

  15. The effect of short term neo-adjuvant androgen deprivation on erectile function in patients treated with external beam radiotherapy for localised prostate cancer: an analysis of the 4- versus 8-month randomised trial (Irish Clinical Oncology Research Group 97-01).

    LENUS (Irish Health Repository)

    Daly, Patricia E

    2012-07-01

    Erectile dysfunction is a common consequence of external beam radiotherapy (EBRT) for prostate cancer. The addition of neo-adjuvant androgen deprivation (NAD) has an indeterminate additive effect. We examined the long-term effect on erectile function (EF) of two durations (4 months: arm 1 and 8 months: arm 2) of NAD prior to radiation (RT) for patients with localised prostate cancer from the Irish Clinical Oncology Research Group (ICORG 97-01) 4- versus 8-month trial. In this study we aimed to (1) analyse the overall effect on EF of NAD in an EBRT population, (2) compare the probability of retained EF over time in an EBRT population treated with either 4 or 8 months of NAD and (3) identify any variables such as risk group and age which may have an additive detrimental effect. This analysis provides unique long term follow up data.

  16. The 'Timing of Androgen-Deprivation therapy in incurable prostate cancer' protocol (TOAD)--where are we now? Synopsis of the Victorian Cooperative Oncology Group PR 01-03 and Trans-Tasman Radiation Oncology Group 03.06 clinical trial.

    Science.gov (United States)

    Duchesne, Gillian M; Woo, Henry H

    2014-11-01

    To outline the development of the 'Timing of Androgen Deprivation' (TOAD) protocol, a collaborative randomised clinical trial under the auspices of the Cancer Council Victoria, the Trans-Tasman Radiation Oncology Group, and the Urological Society of Australia and New Zealand (USANZ), which opened to recruitment in 2004. The principal hypothesis for the trial was that the early introduction of androgen-deprivation therapy (ADT; experimental arm) at the time when curative therapies are no longer considered an option, would improve overall survival for these patients, whilst maintaining an acceptable quality of life; compared with waiting for disease progression or the development of symptoms (control arm). An increase in overall survival at 5 years of 10% was judged to be clinically worthwhile. Recruitment was slow, with fewer than half of the protocol requirement of 750 patients eventually accrued, but nonetheless it is considered that the trial will still contribute a major source of evidence in this area. The study closed to follow-up at the end of 2013, with data analysis commencing mid-2014, and with the primary publication anticipated to be submitted by the end of 2014. The question of timing of ADT remains relevant in the current era of newer and more varied treatment methods. Even with the advent of novel chemotherapy and the biological agents that are undergoing investigation for progressively earlier disease stages, the dilemma of when to commence palliative treatment in an asymptomatic patient will remain, unless or until these agents are shown to increase overall survival. The TOAD trial will contribute to answering at least in part, some of these questions. © 2014 The Authors. BJU International © 2014 BJU International.

  17. Androgen regulation of prostate cancer: where are we now?

    Science.gov (United States)

    Corona, G; Baldi, E; Maggi, M

    2011-03-01

    Androgens play an essential role in the development and differentiation of the prostate gland; their contribution to pathological conditions, such as benign prostatic hyperplasia and prostate cancer (PC), remains unclear. We reviewed relationships between androgens and the prostate both in physiological and pathological conditions. A systematic search of published evidence was performed using Medline (1969 to September 2010). Androgen-dependency of prostate growth is evident only in the hypogonadal condition, but not in the eugonadal state (the "saturation hypothesis"). There is unequivocal evidence that reducing androgen signaling to the hypogonadal range can reduce PC growth and patient symptoms. At physiological testosterone concentration there is no link between androgen levels and PC risk. In addition, different strategies of androgen deprivation (ADT) for advanced PC are only palliative and rarely cure patients. Preliminary evidence indicates that a low androgen milieu is associated with tumor aggressiveness. Transition to androgen-independence is complex and involves both selection and outgrowth of preexisting androgen resistant clones, as well as adaptative upregulation of genes that help the cancer cells to survive and grow after ADT. Because androgens are essential for the regulation of fat distribution, insulin sensitivity, and lipid and bone metabolism, recent publications have highlighted the concept that ADT may also be involved with an increase in overall, as well as cardiovascular, morbidity and mortality. While ADT still represents a cornerstone for the palliative therapy of a small fraction of aggressive PC, a "misuse and/or abuse" of ADT should be avoided.

  18. Androgen insensitivity syndrome: gonadal androgen receptor activity

    International Nuclear Information System (INIS)

    Coulam, C.B.; Graham, M.L.; Spelsberg, T.C.

    1984-01-01

    To determine whether abnormalities of the androgen receptor previously observed in skin fibroblasts from patients with androgen insensitivity syndrome also occur in the gonads of affected individuals, androgen receptor activity in the gonads of a patient with testicular feminization syndrome was investigated. Using conditions for optimal recovery of androgen receptor from human testes established by previous studies, we detected the presence of a high-affinity (dissociation constant . 3.2 X 10(-10) mol/L), low-capacity (4.2 X 10(-12) mol/mg DNA), androgen-binding protein when tritium-labeled R1881 was incubated at 4 degrees C with nuclear extracts from the gonads of control patients or from a patient with testicular feminization syndrome but not when incubated at 37 degrees C. Thus this patient has an androgen receptor with a temperature lability similar to that of receptors from normal persons

  19. Intermittency '93

    International Nuclear Information System (INIS)

    Bialas, A.

    1993-01-01

    The existing data definitely indicate the existence of intermittency, i.e. of self similar structures in the systems of particles created in high-energy collisions. The effect seems universal: it was found in most of the processes investigated and its measures parameters depend only weakly (if at all) on the process in question. Strong HBT effect was found, suggesting that intermittency is related to space-time structure of the pion source rather than to detailed momentum structure of the production amplitudes. There are indications that this space time structure may be fractal, but more data is needed to establish this. The theoretical explanation remains obscure: it seems that both parton cascade and hadronization play an important role. Their interrelation, however, remains a mystery. 5 figs., 19 refs

  20. Intermittent hyperthyreosis

    International Nuclear Information System (INIS)

    Sulman, F.G.; Tal, E.; Pfeifer, Y.; Superstine, E.

    1975-01-01

    Intermittent hyperthyreosis occurs under various forms of stress, especially heat stress. The clinician may diagnose such cases as masked or apathetic hyperthyroidism or 'forme fruste' hyperthyreosis or thyroid autonomy. As most routine and standard tests may here yield inconsistent results, it is the patients' anamnesis which may provide the clue. Our Bioclimatology Unit has now seen over 100 cases in which thyroid hypersensitivity towards heat was the most prominent syndrome: 10-15% of weather-sensitive patients are affected. The patients complain before or during heat spells of such contradictory symptoms as insomnia, irritability, tension, tachycardia, palpitations, precordial pain, dyspnoe, flushes with sweating or chills, tremor, abdominal pain or diarrhea, polyuria or pollakisuria, weight loss in spite of ravenous appetite, fatigue, exhaustion, depression, adynamia, lack of concentration and confusion. Determination of urinary neurohormones allows a differential diagnosis, intermittent hyperthyreosis being characterized by three cardinal symptoms: tachycardia - every case with more than 80 pulse beats being suspect (not specific); urinary histamine - every case excreting more than 90 μg/day being suspect. Again the drawback of this test is its lack of specificity, as histamine may also be increased in cases of allergy and spondylitis; urinary thyroxine - every case excreting more than 20 μg/day T-4 being suspect. This is the only specific test. Therapy should make use of lithium carbonate and betablockers. Propyl thiouracil is rarely required. (orig.) [de

  1. Androgen receptor abnormalities

    NARCIS (Netherlands)

    A.O. Brinkmann (Albert); G.G.J.M. Kuiper (George); C. Ris-Stalpers (Carolyn); H.C.J. van Rooij (Henri); G. Romalo (G.); G. Trifiro (Gianluca); E. Mulder (Eppo); L. Pinsky (L.); H.U. Schweikert (H.); J. Trapman (Jan)

    1991-01-01

    markdownabstract__Abstract__ The human androgen receptor is a member of the superfamily of steroid hormone receptors. Proper functioning of this protein is a prerequisite for normal male sexual differentiation and development. The cloning of the human androgen receptor cDNA and the elucidation of

  2. Androgen receptor abnormalities

    NARCIS (Netherlands)

    Brinkmann, A. O.; Kuiper, G. G.; Ris-Stalpers, C.; van Rooij, H. C.; Romalo, G.; Trifiro, M.; Mulder, E.; Pinsky, L.; Schweikert, H. U.; Trapman, J.

    1991-01-01

    The human androgen receptor is a member of the superfamily of steroid hormone receptors. Proper functioning of this protein is a prerequisite for normal male sexual differentiation and development. The cloning of the human androgen receptor cDNA and the elucidation of the genomic organization of the

  3. Androgen receptor phosphorylation

    NARCIS (Netherlands)

    G.G.J.M. Kuiper (George)

    1995-01-01

    textabstractMany physiological processes in organisms are regulated by a relatively small number of steroid honnones. Androgens are the so-called male sex steroid hormones which control growth, differentiation and functions of male reproductive and accessory sex tissues. Androgens are mainly

  4. Bipolar Androgen Therapy for Men With Androgen Ablation Naïve Prostate Cancer: Results From the Phase II BATMAN Study.

    Science.gov (United States)

    Schweizer, Michael T; Wang, Hao; Luber, Brandon; Nadal, Rosa; Spitz, Avery; Rosen, D Marc; Cao, Haiyi; Antonarakis, Emmanuel S; Eisenberger, Mario A; Carducci, Michael A; Paller, Channing; Denmeade, Samuel R

    2016-09-01

    We have previously documented a paradoxical anti-tumor effect when castration-resistant prostate cancer patients were treated with intermittent, high-dose testosterone (i.e., Bipolar Androgen Therapy; BAT). Because, an adaptive increase in androgen receptor expression following chronic androgen deprivation therapy (ADT) may underlie this effect, we tested whether men with hormone-sensitive (HS) prostate cancer (PC) would also respond to BAT if given following a 6-month ADT lead-in. Asymptomatic HS PC patients with low metastatic burden or non-metastatic biochemically recurrent disease were enrolled. Following 6-month of ADT, those with a PSA <4 ng/ml went on to receive alternating 3-month cycles of BAT and ADT. BAT was administered as intramuscular testosterone (T) cypionate or enanthate 400 mg on Days (D) 1, 29, and 57. ADT was continued throughout the study to allow rapid cycling from near castrate to supraphysiologic range T following T injections. The primary endpoint was the percent of patients with a PSA <4 ng/ml after 18 months. Secondary endpoints included radiographic response and quality of life (QoL). Twenty-nine of 33 patients received BAT following the ADT lead-in. The primary endpoint was met, with 17/29 men (59%, 90% confidence interval: 42-74%) having a PSA <4 ng/ml at 18 months. Ten patients receiving BAT had RECIST evaluable disease, and eight (80%) objective responses were observed (four complete; four partial). Three patients progressed per RECIST criteria and three had unconfirmed progression on bone scan. Men treated with 6-month of ADT had improved QoL following the first cycle of BAT as measured by the SF-36, FACT-P, and IIEF surveys. BAT demonstrated preliminary efficacy in men with HS PC following 6-month of ADT. BAT may improve QoL in men treated with ADT. Prostate 76:1218-1226, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Sphingosine kinase-1 is central to androgen-regulated prostate cancer growth and survival.

    Directory of Open Access Journals (Sweden)

    Audrey Dayon

    Full Text Available BACKGROUND: Sphingosine kinase-1 (SphK1 is an oncogenic lipid kinase notably involved in response to anticancer therapies in prostate cancer. Androgens regulate prostate cancer cell proliferation, and androgen deprivation therapy is the standard of care in the management of patients with advanced disease. Here, we explored the role of SphK1 in the regulation of androgen-dependent prostate cancer cell growth and survival. METHODOLOGY/PRINCIPAL FINDINGS: Short-term androgen removal induced a rapid and transient SphK1 inhibition associated with a reduced cell growth in vitro and in vivo, an event that was not observed in the hormono-insensitive PC-3 cells. Supporting the critical role of SphK1 inhibition in the rapid effect of androgen depletion, its overexpression could impair the cell growth decrease. Similarly, the addition of dihydrotestosterone (DHT to androgen-deprived LNCaP cells re-established cell proliferation, through an androgen receptor/PI3K/Akt dependent stimulation of SphK1, and inhibition of SphK1 could markedly impede the effects of DHT. Conversely, long-term removal of androgen support in LNCaP and C4-2B cells resulted in a progressive increase in SphK1 expression and activity throughout the progression to androgen-independence state, which was characterized by the acquisition of a neuroendocrine (NE-like cell phenotype. Importantly, inhibition of the PI3K/Akt pathway--by negatively impacting SphK1 activity--could prevent NE differentiation in both cell models, an event that could be mimicked by SphK1 inhibitors. Fascinatingly, the reversability of the NE phenotype by exposure to normal medium was linked with a pronounced inhibition of SphK1 activity. CONCLUSIONS/SIGNIFICANCE: We report the first evidence that androgen deprivation induces a differential effect on SphK1 activity in hormone-sensitive prostate cancer cell models. These results also suggest that SphK1 activation upon chronic androgen deprivation may serve as a

  6. Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer.

    OpenAIRE

    Asim, Mohammad; Tarish, Firas; Zecchini, Heather I; Sanjiv, Kumar; Gelali, Eleni; Massie, Charles Edward; Baridi, Ajoeb; Warren, Anne Y; Zhao, Wanfeng; Ogris, Christoph; McDuffus, Leigh-Anne; Mascalchi, Patrice; Shaw, Greg; Dev, Harveer; Wadhwa, Karan

    2017-01-01

    Emerging data demonstrate homologous recombination (HR) defects in castration resistant prostate cancers, rendering these tumours sensitive to PARP inhibition. Here, we demonstrate a direct requirement for the androgen receptor (AR) to maintain HR gene expression and HR activity in prostate cancer. We show that PARP-mediated repair pathways are upregulated in prostate cancer following androgen-deprivation therapy (ADT). Furthermore, upregulation of PARP activity is essential for the survival...

  7. Molecular basis of androgen insensitivity

    NARCIS (Netherlands)

    Brinkmann, A.; Jenster, G.; Ris-Stalpers, C.; van der Korput, H.; Brüggenwirth, H.; Boehmer, A.; Trapman, J.

    1996-01-01

    Male sexual differentiation and development proceed under direct control of androgens. Androgen action is mediated by the intracellular androgen receptor, which belongs to the superfamily of ligand-dependent transcription factors. In the X-linked androgen insensitivity syndrome, defects in the

  8. Ovarian overproduction of androgens

    Science.gov (United States)

    ... an ovarian or adrenal tumor. Outlook (Prognosis) Treatment success depends on the cause of excess androgen production. ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

  9. Androgens and menopause.

    Science.gov (United States)

    Shulman, L P

    2009-12-01

    The cessation of ovarian sex steroidigenesis, either as result as surgical extirpation, certain medical therapies or the gradual cessation of ovarian function, leads to menopause with all its associated physiological, physical and lifestyle changes. The changing hormonal milieu of menopause is most commonly associated with declining levels of estrogens. However, ovarian senescence also results in declining levels of androgens. Indeed, it is the loss of physiological levels of estrogens and androgens that result in the varied signs and symptoms of menopause including vasomotor symptoms, bone mineral density loss, reduced interest in sex, alterations in mood and energy and hair loss, among others. This paper will provide a review of the role of androgens in the menopause and assess the potential of androgen therapies in the management of the menopause.

  10. Therapeutic androgen receptor ligands

    Science.gov (United States)

    Allan, George F.; Sui, Zhihua

    2003-01-01

    In the past several years, the concept of tissue-selective nuclear receptor ligands has emerged. This concept has come to fruition with estrogens, with the successful marketing of drugs such as raloxifene. The discovery of raloxifene and other selective estrogen receptor modulators (SERMs) has raised the possibility of generating selective compounds for other pathways, including androgens (that is, selective androgen receptor modulators, or SARMs). PMID:16604181

  11. Interocular suppression in children with deprivation amblyopia.

    Science.gov (United States)

    Hamm, Lisa; Chen, Zidong; Li, Jinrong; Black, Joanna; Dai, Shuan; Yuan, Junpeng; Yu, Minbin; Thompson, Benjamin

    2017-04-01

    In patients with anisometropic or strabismic amblyopia, interocular suppression can be minimized by presenting high contrast stimulus elements to the amblyopic eye and lower contrast elements to the fellow eye. This suggests a structurally intact binocular visual system that is functionally suppressed. We investigated whether suppression can also be overcome by contrast balancing in children with deprivation amblyopia due to childhood cataracts. To quantify interocular contrast balance, contrast interference thresholds were measured using an established dichoptic global motion technique for 21 children with deprivation amblyopia, 14 with anisometropic or mixed strabismic/anisometropic amblyopia and 10 visually normal children (mean age mean=9.9years, range 5-16years). We found that interocular suppression could be overcome by contrast balancing in most children with deprivation amblyopia, at least intermittently, and all children with anisometropic or mixed anisometropic/strabismic amblyopia. However, children with deprivation amblyopia due to early unilateral or bilateral cataracts could tolerate only very low contrast levels to the stronger eye indicating strong suppression. Our results suggest that treatment options reliant on contrast balanced dichoptic presentation could be attempted in a subset of children with deprivation amblyopia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Muscle Dysfunction in Androgen Deprivation: Role of Ryanodine Receptor

    Science.gov (United States)

    2016-11-01

    Lamb GD, Westerblad H . Skeletal muscle fatigue: cellular mechanisms. Physiol Rev. Jan 2008;88(1):287-332. 15. Bellinger AM, Reiken S...than aged sham mice (p=0.0016, 2way ANOVA). Body Weight Young Mice Time (weeks) % c h a n g e b o d y w e ig h t 0 5 10 15 20 0 10 20 30 40...50 ORX SHAM Body Weight Aged Mice Time (weeks) % c h a n g e b o d y w e ig h t 5 10 15 -20 -10 0 10 ORX SHAM p = 0.0016 Fat

  13. Characterizing Mechanisms of Resistance to Androgen Deprivation in Prostate Cancer

    Science.gov (United States)

    2015-11-01

    targeted CRISPR genomic editing technology. Cas9 - expressing LNcaP cells were infected with small guides targeting the AR gene. Unfortunately, only...of AR using IPTG-inducible constructs. Figure 5. CRISPR -driven INPP5A knock-out (A) Immunoblot of INPP5A showing CRISPR - Cas9 knock out of...endogenous INPP5A in LNCaP cells. (B) CRISPR - Cas9 KO of endogenous INPP5A in LNCaP cells drives proliferation in CSS medium. (C) AR and PSA levels in INPP5A

  14. Intermittent Explosive Disorder

    OpenAIRE

    Lut Tamam; Meliha Zengin Eroglu; Ozlem Paltaci

    2011-01-01

    Intermittent explosive disorder is an impulse control disorder characterized by the occurrence of discrete episodes of failure to resist aggressive impulses that result in violent assault or destruction of property. Though the prevalence intermittent explosive disorder has been reported to be relatively rare in frontier studies on the field, it is now common opinion that intermittent explosive disorder is far more common than previously thought especially in clinical psychiatry settings. Etio...

  15. Androgen secreting adrenocortical tumours.

    Science.gov (United States)

    Wolthers, O D; Cameron, F J; Scheimberg, I; Honour, J W; Hindmarsh, P C; Savage, M O; Stanhope, R G; Brook, C G

    1999-01-01

    Androgen secreting adrenocortical tumours are rare in children and the determination of their malignant potential can be difficult. To assess the presentation, histology, and clinical behaviour of these tumours. Two tertiary referral centres. Retrospective analysis of children diagnosed with an androgen secreting adrenocortical tumour between 1976 and 1996. Twenty three girls and seven boys aged 0-14 years. Pubic hair was observed in all children, clitoromegaly or growth of the phallus in 23 children, acceleration of linear growth in 22 children, and advanced bone age (> 1.5 years) in 18 children. Hypersecretion of androgens was detected by assessment of serum androgen concentrations alone in four patients and by 24 hour urine steroid excretion profiles in 22 patients. All 16 tumours measuring 10 cm were malignant. Histological slides were available for reassessment in 25 children. Although mitoses and necrosis were more characteristic of tumours with malignant behaviour, no exclusive histological features of malignancy were seen. Histological criteria for malignancy are not reliable, whereas tumour size is important in assessing malignant potential.

  16. Evolving perspectives of the role of novel agents in androgen-independent prostate cancer

    Directory of Open Access Journals (Sweden)

    Sujith Kalmadi

    2008-01-01

    Full Text Available Metastatic androgen-independent prostate cancer presents an intriguing clinical challenge, with a subtle interaction between hormone-responsive and refractory tumor cell elements. The treatment of advanced prostate carcinoma, which had remained stagnant for several decades following the understanding of the link between androgenic stimulation and carcinogenesis, has now started to make steady headway with chemotherapy and targeted approaches. Metastatic prostate cancer is almost always treated with initial androgen deprivation, in various forms. However, despite such treatment androgen-independent prostate cancer cells eventually emerge and progress to threaten life. The therapeutic objectives for treatment of metastatic prostate cancer are to maintain the quality of life and prolong survival. The out-dated nihilistic dogma of deferring chemotherapy until the most advanced stages in advanced prostate cancer is now falling by the wayside with the development of newer effective, tolerable agents.

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

    Science.gov (United States)

    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

  18. Summarizing multiple deprivation indicators

    OpenAIRE

    Cappellari, Lorenzo; Jenkins, Stephen P.

    2006-01-01

    Deprivation scales derived from multiple, typically dichotomous, indicators, are widely used to monitor households’ standards of living, and to complement measures of living standards based on income. We use an item response modelling (IRM) framework to address several issues concerning the derivation of deprivation scales in general and the use of sum-score deprivation indices in particular. Although we favour the IRM approach over the sum-score one in principle, we find in an illustrative...

  19. Deprivation and Social Exclusion

    OpenAIRE

    BOSSERT, Walter; D'AMBROSIO, Conchita; PERAGINE, Vito

    2004-01-01

    Social exclusion manifests itself in the lack of an individual’s access to functionings as compared to other members of society. Thus, the concept is closely related to deprivation. We view deprivation as having two basic determinants: the lack of identification with other members of society and the aggregate alienation experienced by an agent with respect to those with fewer functioning failures. We use an axiomatic approach to characterize classes of deprivation and exclusion measures and a...

  20. Genetics Home Reference: androgen insensitivity syndrome

    Science.gov (United States)

    ... allow cells to respond to androgens, which are hormones (such as testosterone ) that direct male sexual development. Androgens and androgen receptors also have other important functions in both males and females, such as regulating ...

  1. Metabolic syndrome in androgenic alopecia.

    Science.gov (United States)

    Gopinath, Hima; Upadya, Gatha M

    2016-01-01

    Androgenic alopecia has been associated with an increased risk of coronary heart disease in various studies. The relationship between androgenic alopecia and metabolic syndrome, a known risk factor for atherosclerotic cardiovascular disease, is still poorly understood. To study the association between metabolic syndrome and early-onset androgenic alopecia. A hospital-based analytical cross-sectional study was done on men in the age group of 18-55 years. Eighty five clinically diagnosed cases with early-onset (alopecia of Norwood grade III or above, and 85 controls without androgenic alopecia were included. Data collected included anthropometric measurements, arterial blood pressure and history of chronic diseases. Fasting blood and lipid profile were determined. Metabolic syndrome was diagnosed as per the new International Diabetes Federation criteria. Chi-square and Student's t-test were used for statistical analysis using Statistical Package for the Social Sciences (SPSS) version 17.00. Metabolic syndrome was seen in 19 (22.4%) patients with androgenic alopecia and 8 (9.4%) controls (P = 0.021). Abdominal obesity, hypertension and lowered high-density lipoprotein were significantly higher in patients with androgenic alopecia versus their respective controls. The limitations of our study include small sample size in subgroups and the lack of evidence of a temporal relationship between metabolic syndrome and androgenic alopecia. A higher prevalence of metabolic syndrome is seen in men with early-onset androgenic alopecia. Early screening for metabolic syndrome and its components is beneficial in patients with early-onset androgenic alopecia.

  2. Private deprivation of liberty.

    Science.gov (United States)

    Griffith, Richard

    2017-04-02

    The Court of Appeal has ruled that a person is deprived of their liberty in their own home even though care and treatment was provided in the person's own home and funded using the person's money. In this article Richard Griffith discusses when a private deprivation of liberty must be authorised by a welfare order from the Court of Protection.

  3. Intermittent Explosive Disorder

    Science.gov (United States)

    ... Headache Intermittent explosive disorder Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  4. Intermittent Explosive Disorder

    Directory of Open Access Journals (Sweden)

    Lut Tamam

    2011-09-01

    Full Text Available Intermittent explosive disorder is an impulse control disorder characterized by the occurrence of discrete episodes of failure to resist aggressive impulses that result in violent assault or destruction of property. Though the prevalence intermittent explosive disorder has been reported to be relatively rare in frontier studies on the field, it is now common opinion that intermittent explosive disorder is far more common than previously thought especially in clinical psychiatry settings. Etiological studies displayed the role of both psychosocial factors like childhood traumas and biological factors like dysfunctional neurotransmitter systems and genetics. In differential diagnosis of the disorder, disorders involving agression as a symptom such as alcohol and drug intoxication, antisocial and borderline personality disorders, personality changes due to general medical conditions and behavioral disorder should be considered. A combination of pharmacological and psychotherapeutic approaches are suggested in the treatment of the disorder. This article briefly reviews the historical background, diagnostic criteria, epidemiology, etiology and treatment of intermittent explosive disorder.

  5. Androgen deprivation with or without radiation therapy for clinically node-positive prostate cancer. Lin CC, Gray PJ, Jemal A, Efstathiou JA, Surveillance and Health Services Research Program, Intramural Research, American Cancer Society, Atlanta, GA (CCL, AJ); Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (PJG, JAE); e-mail: jefstathiou@partners.org. J Natl Cancer Inst. 2015 May 9;107(7). pii: djv119. [Print 2015 Jul]. doi: 10.1093/jnci/djv119.

    Science.gov (United States)

    Scott, Eggener

    2017-03-01

    Clinically lymph node-positive (cN+) prostate cancer (PCa) is an often-fatal disease. Its optimal management remains largely undefined given a lack of prospective, randomized data to inform practice. We sought to describe modern practice patterns in the management of cN+PCa and assess the effect of adding radiation therapy (RT) to androgen deprivation therapy (ADT) on survival using the National Cancer Data Base. Patients with cN+PCa and without distant metastases diagnosed between 2004 and 2011 were included. Five-year overall survival for patients diagnosed between 2004 and 2006 and treated with ADT alone or ADT+RT were compared. Propensity score (PS) matching was used to balance baseline characteristics, and Cox multivariate regression analysis was used to estimate hazard ratios (HRs) for all-cause mortality. Of 3,540 total patients, 32.2% were treated with ADT alone and 51.4% received ADT+RT. Compared with ADT alone, patients treated with ADT+RT were younger and more likely to have private insurance, lower comorbidity scores, higher Gleason scores, and lower PSA values. After PS matching, 318 patients remained in each group. Compared with ADT alone, ADT+RT was associated with a 50% decreased risk of five-year all-cause mortality (HR = 0.50, 95% CI: 0.37-0.67, two-sided P<0.001; crude OS rate: 71.5% vs. 53.2%). Using a large national database, we have identified a statistically significant survival benefit for patients with cN+PCa treated with ADT+RT. These data, if appropriately validated by randomized trials, suggest that a substantial proportion of such patients at high risk for prostate cancer death may be undertreated, warranting a reevaluation of current practice guidelines. Copyright © 2017. Published by Elsevier Inc.

  6. Was cultural deprivation in fact sensory deprivation? Deprivation, retardation and intervention in the USA.

    Science.gov (United States)

    Raz, Mical

    2011-01-01

    In the 1950s, the term "deprivation" entered American psychiatric discourse. This article examines how the concept of deprivation permeated the field of mental retardation, and became an accepted theory of etiology. It focuses on sensory deprivation and cultural deprivation, and analyzes the interventions developed, based on these theories. It argues that the controversial theory of cultural deprivation derived its scientific legitimization from the theory of sensory deprivation, and was a highly politicized concept that took part in the nature-nurture debate.

  7. Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Villagran, Marcelo A.; Gutierrez-Castro, Francisco A.; Pantoja, Diego F.; Alarcon, Jose C.; Fariña, Macarena A.; Amigo, Romina F.; Muñoz-Godoy, Natalia A. [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Pinilla, Mabel G. [Department of Medical Specialties, School of Medicine, University of Concepcion, Concepcion (Chile); Peña, Eduardo A.; Gonzalez-Chavarria, Ivan; Toledo, Jorge R.; Rivas, Coralia I.; Vera, Juan C. [Department of Physiopathology, School of Biological Sciences, University of Concepcion, Concepcion (Chile); McNerney, Eileen M. [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Onate, Sergio A., E-mail: sergio.onate@udec.cl [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Department of Medical Specialties, School of Medicine, University of Concepcion, Concepcion (Chile); Department of Urology, State University of New York at Buffalo, NY (United States)

    2015-11-27

    Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells. - Highlights: • Decreased corepressor expression change AR in androgen-resistance prostate cancer. • Bone stroma-derived cells change AR coregulator recruitment in prostate cancer. • Bone stroma cells change cell proliferation in androgen-resistant cancer cells. • Global gene expression in CaP cells is modified by bone stroma cells in co

  8. Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells

    International Nuclear Information System (INIS)

    Villagran, Marcelo A.; Gutierrez-Castro, Francisco A.; Pantoja, Diego F.; Alarcon, Jose C.; Fariña, Macarena A.; Amigo, Romina F.; Muñoz-Godoy, Natalia A.; Pinilla, Mabel G.; Peña, Eduardo A.; Gonzalez-Chavarria, Ivan; Toledo, Jorge R.; Rivas, Coralia I.; Vera, Juan C.; McNerney, Eileen M.; Onate, Sergio A.

    2015-01-01

    Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells. - Highlights: • Decreased corepressor expression change AR in androgen-resistance prostate cancer. • Bone stroma-derived cells change AR coregulator recruitment in prostate cancer. • Bone stroma cells change cell proliferation in androgen-resistant cancer cells. • Global gene expression in CaP cells is modified by bone stroma cells in co

  9. Androgens and androgen receptor action in skin and hair follicles.

    Science.gov (United States)

    Ceruti, Julieta María; Leirós, Gustavo José; Balañá, María Eugenia

    2018-04-15

    Beyond sexual functions, androgens exert their action in skin physiology and pathophysiology. Skin cells are able to synthesize most active androgens from gonadal or adrenal precursors and the enzymes involved in skin steroidogenesis are implicated both in normal or pathological processes. Even when the role of androgens and androgen receptor (AR) in skin pathologies has been studied for decades, their molecular mechanisms in skin disorders remain largely unknown. Here, we analyze recent studies of androgens and AR roles in several skin-related disorders, focusing in the current understanding of their molecular mechanisms in androgenetic alopecia (AGA). We review the molecular pathophysiology of type 2 5α-reductase, AR coactivators, the paracrine factors deregulated in dermal papillae (such as TGF-β, IGF 1, WNTs and DKK-1) and the crosstalk between AR and Wnt signaling in order to shed some light on new promising treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. [Diabetes and social deprivation].

    Science.gov (United States)

    Jaffiol, Claude; Fontbonne, Annick; Vannereau, Denyse; Olive, Jean-Paul; Passeron, Serge

    2012-01-01

    Diabetes prevalence is frequently associated with low socioeconomic status (SES), but little is known about the relationship between SES and diabetes control, follow-up and quality of life. We evaluated SES by using the EPICES score, an individual index of deprivation (Evaluation de la Précarité et des Inégalités de Santé dans les Centres d'Examen de Santé; Evaluation of Precariousness and Inequalities in Health Examination Centers). A total of 1686 subjects aged from 25 to 85 years were selected at random in Montpellier and 154 in Narbonne, of whom 126 were managed by a care network including diabetologists, general practitioners and nurses. Capillary glycemia, the body mass index (BMI), waist circumference (WC), and blood pressure were measured in all the subjects. HbA1c was measured in subjects with above-normal glycemia. Five hundred sixty-four subjects from the study population (190 diabetic patients, 292 subjects with non diabetic hyperglycemia, and 86 euglycemic subjects) were clinically evaluated and asked to complete a questionnaire covering socioeconomic status and diet. The data were then compared between deprived and non deprived subjects. One hundred sixty-one diabetic patients had a clinical examination and completed a detailed questionnaire including their history, therapy, control and follow-up of diabetes, perception of diabetes, quality of life, socioeconomic status and diet. The data were then compared between deprived and non deprived patients. One hundred twenty-six diabetic subjects managed by the AUDIAB care network were compared with 163 diabetics recruited in Montpellier, based on the same investigations and the same questionnaires. The data were compared between the overall patients and between deprived and non deprived patients. In the overall population, deprived subjects were younger and more frequently smokers, and had higher BMI than non deprived subjects. The overall prevalence of type 2 diabetes was 8.1%. Among patients

  11. A novel selective androgen receptor modulator (SARM) MK-4541 exerts anti-androgenic activity in the prostate cancer xenograft R-3327G and anabolic activity on skeletal muscle mass & function in castrated mice.

    Science.gov (United States)

    Chisamore, Michael J; Gentile, Michael A; Dillon, Gregory Michael; Baran, Matthew; Gambone, Carlo; Riley, Sean; Schmidt, Azriel; Flores, Osvaldo; Wilkinson, Hilary; Alves, Stephen E

    2016-10-01

    The androgen receptor (AR) is a member of the nuclear hormone receptor super family of transcription factors. Androgens play an essential role in the development, growth, and maintenance of male sex organs, as well as the musculoskeletal and central nervous systems. Yet with advancing age, androgens can drive the onset of prostate cancer, the second leading cause of cancer death in males within the United States. Androgen deprivation therapy (ADT) by pharmacologic and/or surgical castration induces apoptosis of prostate cells and subsequent shrinkage of the prostate and prostate tumors. However, ADT is associated with significant musculoskeletal and behavioral adverse effects. The unique pharmacological activity of selective androgen receptor modulator (SARM) MK-4541 recently has been reported as an AR antagonist with 5α-reductase inhibitor function. The molecule inhibits proliferation and induces apoptosis in AR positive, androgen dependent prostate cancer cells. Importantly, MK-4541 inhibited androgen-dependent prostate growth in male rats yet maintained lean body mass and bone formation following ovariectomy in female rats. In the present study, we evaluated the effects of SARM MK-4541 in the androgen-dependent Dunning R3327-G prostate carcinoma xenograft mouse model as well as on skeletal muscle mass and function, and AR-regulated behavior in mice. MK-4541 significantly inhibited the growth of R3327-G prostate tumors, exhibited anti-androgen effects on the seminal vesicles, reduced plasma testosterone concentrations in intact males, and inhibited Ki67 expression. MK-4541 treated xenografts appeared similar to xenografts in castrated mice. Importantly, we demonstrate that MK-4541 exhibited anabolic activity in androgen deficient conditions, increasing lean body mass and muscle function in adult castrated mice. Moreover, MK-4541 treatment restored general activity levels in castrated mice. Thus, MK-4541 exhibits an optimum profile as an adjuvant therapy to ADT

  12. Identification of an anabolic selective androgen receptor modulator that actively induces death of androgen-independent prostate cancer cells.

    Science.gov (United States)

    Schmidt, Azriel; Meissner, Robert S; Gentile, Michael A; Chisamore, Michael J; Opas, Evan E; Scafonas, Angela; Cusick, Tara E; Gambone, Carlo; Pennypacker, Brenda; Hodor, Paul; Perkins, James J; Bai, Chang; Ferraro, Damien; Bettoun, David J; Wilkinson, Hilary A; Alves, Stephen E; Flores, Osvaldo; Ray, William J

    2014-09-01

    Prostate cancer (PCa) initially responds to inhibition of androgen receptor (AR) signaling, but inevitably progresses to hormone ablation-resistant disease. Much effort is focused on optimizing this androgen deprivation strategy by improving hormone depletion and AR antagonism. However we found that bicalutamide, a clinically used antiandrogen, actually resembles a selective AR modulator (SARM), as it partially regulates 24% of endogenously 5α-dihydrotestosterone (DHT)-responsive genes in AR(+) MDA-MB-453 breast cancer cells. These data suggested that passive blocking of all AR functions is not required for PCa therapy. Hence, we adopted an active strategy that calls for the development of novel SARMs, which induce a unique gene expression profile that is intolerable to PCa cells. Therefore, we screened 3000 SARMs for the ability to arrest the androgen-independent growth of AR(+) 22Rv1 and LNCaP PCa cells but not AR(-) PC3 or DU145 cells. We identified only one such compound; the 4-aza-steroid, MK-4541, a potent and selective SARM. MK-4541 induces caspase-3 activity and cell death in both androgen-independent, AR(+) PCa cell lines but spares AR(-) cells or AR(+) non-PCa cells. This activity correlates with its promoter context- and cell-type dependent transcriptional effects. In rats, MK-4541 inhibits the trophic effects of DHT on the prostate, but not the levator ani muscle, and triggers an anabolic response in the periosteal compartment of bone. Therefore, MK-4541 has the potential to effectively manage prostatic hypertrophic diseases owing to its antitumor SARM-like mechanism, while simultaneously maintaining the anabolic benefits of natural androgens. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. ANDROGEN LEVELS IN PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    M. Valadan

    2006-08-01

    Full Text Available Preeclampsia is a major cause of morbidity and mortality during pregnancy. Several independent investigators have demonstrated the association of androgens with hypertension. The main purpose of this study was to determine whether maternal levels of sex hormones, especially testosterone, are higher in patients with preeclampsia than in matched normotensive control subjects. Serum levels of testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEA-S and estradiol were measured in 60 subjects in the 3rd trimester of pregnancy with documented preeclampsia (including 30 cases of mild and 30 cases of severe preeclampsia and 60 healthy normotensive women with similar maternal and gestational ages and body mass index (BMI and neonatal sex. All subjects were primigravid with singleton pregnancies. Cases of polycystic ovary (PCO, diabetes, chronic hypertension and chronic systemic diseases such as lupus and patients using steroid hormones and anti-hypertensive drugs were excluded. Levels of testosterone, DHEA-S and estradiol were not higher in primigravid women with preeclampsia than in normotensive women with similar gestational and maternal ages, BMI and neonatal sex. There were no significant differences in sex hormones measured between groups of mild and severe preeclampsia and normotensive women. There were also no significant differences in sex hormone levels according to neonatal sex. These findings are against the hypothesis of mediating or amplifying role of high androgen levels in pathophysiology of preeclampsia.

  14. [Neurogenic intermittent claudication].

    Science.gov (United States)

    Jarmundowicz, W; Haftek, J

    1984-01-01

    In the period 1971-1981 operations were carried out in 1114 cases of discopathy or lumbar spondylosis. Three patients in this group had pains of the type of intermittent claudication as the main symptoms. In all these cases narrowing of the vertebral canal was found in the lumbar part caused in two cases by degenerative changes and herniation of the intervertebral discs, and in a third case it was due to an extensive connective tissue scar at the site of previously done laminectomy. The nerve roots of the cauda were relieved from pressure surgically and in all cases pains disappeared. The authors discuss factors contributing to the development of neurogenic intermittent claudication.

  15. New Insights into the Androgen-Targeted Therapies and Epigenetic Therapies in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Abhijit M. Godbole

    2011-01-01

    Full Text Available Prostate cancer is the most common cancer in men in the United States, and it is the second leading cause of cancer-related death in American men. The androgen receptor (AR, a receptor of nuclear family and a transcription factor, is the most important target in this disease. While most efforts in the clinic are currently directed at lowering levels of androgens that activate AR, resistance to androgen deprivation eventually develops. Most prostate cancer deaths are attributable to this castration-resistant form of prostate cancer (CRPC. Recent work has shed light on the importance of epigenetic events including facilitation of AR signaling by histone-modifying enzymes, posttranslational modifications of AR such as sumoylation. Herein, we provide an overview of the structure of human AR and its key structural domains that can be used as targets to develop novel antiandrogens. We also summarize recent findings about the antiandrogens and the epigenetic factors that modulate the action of AR.

  16. Effects of sleep deprivation and exercise on cognitive, motor performance and mood.

    Science.gov (United States)

    Scott, Jonathon P R; McNaughton, Lars R; Polman, Remco C J

    2006-02-28

    This study examined the effect of 30 h of sleep deprivation and intermittent physical exercise, on both cognitive and psychomotor function as well subjective ratings of mood. Six subjects with the following physical characteristics participated in the study (Mean +/- S.D.): age 22 +/- 0.3 years, height 180 +/- 5 cm, body mass: 77 +/- 5 kg, VO2peak 44 +/- 5 ml kg(-1) min(-1). Three subjects engaged in normal sedentary activities while three others cycled on a cycle ergometer at 50% VO2peak for 20 min out of every 2 h during 30 h of sleep deprivation. One week later sleep deprivation was repeated with a cross over of subjects. Every 4 h, subjects completed simple and two-choice reaction time tasks at both rest and during exercise, a computerized tracking task, a number cancellation task, and an assessment of subjective mood state as measured by the POMS questionnaire. A 3 x 4 repeated measures ANOVA revealed that resting but not exercising reaction times were significantly slower with sleep deprivation. Sleep deprivation was also associated with significantly greater negative disturbances to subjective vigour, fatigue and depression assessed by the Profile of Mood States questionnaire. Compared to those who have been deprived of sleep alone, individuals that performed 5 h of intermittent moderate exercise during 30 h of sleep deprivation appeared to be more vulnerable to negative mood disturbances and impairment in reaction times. This could result in greater risk of accident due to a reduced capacity to respond quickly.

  17. Fate in intermittent claudication

    DEFF Research Database (Denmark)

    Jelnes, Rolf; Gaardsting, O; Hougaard Jensen, K

    1986-01-01

    The fate of 257 consecutive patients (100 women) aged 36-85 years (mean 65) first seen with intermittent claudication in 1977 was analysed after a mean of 6.5 (SD 0.5) years. When first seen none of the patients complained of rest pain or had ulcers or gangrenous lesions on the feet. At follow up...

  18. Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer.

    Science.gov (United States)

    Asim, Mohammad; Tarish, Firas; Zecchini, Heather I; Sanjiv, Kumar; Gelali, Eleni; Massie, Charles E; Baridi, Ajoeb; Warren, Anne Y; Zhao, Wanfeng; Ogris, Christoph; McDuffus, Leigh-Anne; Mascalchi, Patrice; Shaw, Greg; Dev, Harveer; Wadhwa, Karan; Wijnhoven, Paul; Forment, Josep V; Lyons, Scott R; Lynch, Andy G; O'Neill, Cormac; Zecchini, Vincent R; Rennie, Paul S; Baniahmad, Aria; Tavaré, Simon; Mills, Ian G; Galanty, Yaron; Crosetto, Nicola; Schultz, Niklas; Neal, David; Helleday, Thomas

    2017-08-29

    Emerging data demonstrate homologous recombination (HR) defects in castration-resistant prostate cancers, rendering these tumours sensitive to PARP inhibition. Here we demonstrate a direct requirement for the androgen receptor (AR) to maintain HR gene expression and HR activity in prostate cancer. We show that PARP-mediated repair pathways are upregulated in prostate cancer following androgen-deprivation therapy (ADT). Furthermore, upregulation of PARP activity is essential for the survival of prostate cancer cells and we demonstrate a synthetic lethality between ADT and PARP inhibition in vivo. Our data suggest that ADT can functionally impair HR prior to the development of castration resistance and that, this potentially could be exploited therapeutically using PARP inhibitors in combination with androgen-deprivation therapy upfront in advanced or high-risk prostate cancer.Tumours with homologous recombination (HR) defects become sensitive to PARPi. Here, the authors show that androgen receptor (AR) regulates HR and AR inhibition activates the PARP pathway in vivo, thus inhibition of both AR and PARP is required for effective treatment of high risk prostate cancer.

  19. ANDROGEN REPLACEMENT THERAPY IN POSTMENOPAUSE

    Directory of Open Access Journals (Sweden)

    Helena Meden Vrtovec

    2008-12-01

    Scientific studies and clinical experiences have not provided until now the answers to thequestion: »Whom to treat, when, why and for how long should androgens be used for HRTin postmenopausal women?«

  20. LncRNA HOTAIR Enhances the Androgen-Receptor-Mediated Transcriptional Program and Drives Castration-Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Ali Zhang

    2015-10-01

    Full Text Available Understanding the mechanisms of androgen receptor (AR activation in the milieu of low androgen is critical to effective treatment of castration-resistant prostate cancer (CRPC. Here, we report HOTAIR as an androgen-repressed lncRNA, and, as such, it is markedly upregulated following androgen deprivation therapies and in CRPC. We further demonstrate a distinct mode of lncRNA-mediated gene regulation, wherein HOTAIR binds to the AR protein to block its interaction with the E3 ubiquitin ligase MDM2, thereby preventing AR ubiquitination and protein degradation. Consequently, HOTAIR expression is sufficient to induce androgen-independent AR activation and drive the AR-mediated transcriptional program in the absence of androgen. Functionally, HOTAIR overexpression increases, whereas HOTAIR knockdown decreases, prostate cancer cell growth and invasion. Taken together, our results provide compelling evidence of lncRNAs as drivers of androgen-independent AR activity and CRPC progression, and they support the potential of lncRNAs as therapeutic targets.

  1. Dual-Tasking Alleviated Sleep Deprivation Disruption in Visuomotor Tracking: An fMRI Study

    Science.gov (United States)

    Gazes, Yunglin; Rakitin, Brian C.; Steffener, Jason; Habeck, Christian; Butterfield, Brady; Basner, Robert C.; Ghez, Claude; Stern, Yaakov

    2012-01-01

    Effects of dual-responding on tracking performance after 49-h of sleep deprivation (SD) were evaluated behaviorally and with functional magnetic resonance imaging (fMRI). Continuous visuomotor tracking was performed simultaneously with an intermittent color-matching visual detection task in which a pair of color-matched stimuli constituted a…

  2. Sleep deprivation and false memories.

    Science.gov (United States)

    Frenda, Steven J; Patihis, Lawrence; Loftus, Elizabeth F; Lewis, Holly C; Fenn, Kimberly M

    2014-09-01

    Many studies have investigated factors that affect susceptibility to false memories. However, few have investigated the role of sleep deprivation in the formation of false memories, despite overwhelming evidence that sleep deprivation impairs cognitive function. We examined the relationship between self-reported sleep duration and false memories and the effect of 24 hr of total sleep deprivation on susceptibility to false memories. We found that under certain conditions, sleep deprivation can increase the risk of developing false memories. Specifically, sleep deprivation increased false memories in a misinformation task when participants were sleep deprived during event encoding, but did not have a significant effect when the deprivation occurred after event encoding. These experiments are the first to investigate the effect of sleep deprivation on susceptibility to false memories, which can have dire consequences. © The Author(s) 2014.

  3. Relative deprivation and intergroup prejudice

    NARCIS (Netherlands)

    Pettigrew, T.F.; Christ, O.; Wagner, U.; Meertens, R.W.; van Dick, R.; Zick, A.

    2008-01-01

    Using three diverse European surveys, we test the relationship between relative deprivation (RD) and anti-immigrant prejudice. We find that both group relative deprivation (GRD) and individual relative deprivation (IRD) are found primarily among working-class respondents who are politically

  4. Sleep deprivation and depression

    NARCIS (Netherlands)

    Elsenga, Simon

    1992-01-01

    The association between depression and sleep disturbances is perhaps as old as makind. In view of the longstanding experience with this association it is amazing that only some 20 years ago, a few depressed patients attracted attention to the fact that Total Sleep Deprivation (TSD) had

  5. Are You Sleep Deprived?

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Sleep Disorders Are You Sleep Deprived? Past Issues / Summer 2015 Table of Contents ... even if you think you've had enough sleep? You might have a sleep disorder. There are ...

  6. Andrographolide targets androgen receptor pathway in castration-resistant prostate cancer.

    Science.gov (United States)

    Liu, Chengfei; Nadiminty, Nagalakshmi; Tummala, Ramakumar; Chun, Jae Yeon; Lou, Wei; Zhu, Yezi; Sun, Meng; Evans, Christopher P; Zhou, Qinghua; Gao, Allen C

    2011-02-01

    Androgen receptor (AR) signaling not only plays a pivotal role in the development of androgen-dependent prostate cancer but is also important in the growth and survival of castration-resistant prostate cancer (CRPC). The first line of treatment of androgen-dependent prostate cancer is the use of androgen deprivation therapy. However, most patients will eventually relapse due to development of CRPC. Thus, development of a strategy to target AR for treatment of CRPC is urgently needed. The authors have previously identified andrographolide as an inhibitor of interleukin-6, which can suppress tumor growth of prostate cancer cells by screening compounds from the Prestwick Natural compound library. In this study, they identified that andrographolide can inhibit AR expression and prostate cancer cell growth and induce apoptosis. Andrographolide is able to down-regulate AR expression at both mRNA and protein levels, prevents its nuclear translocation, and inhibits transactivation of its target genes. Andrographolide prevents the binding of Hsp90 to AR, resulting in proteasome-mediated AR degradation. Furthermore, andrographolide inhibits castration-resistant C4-2 cell growth by reducing AR expression and activity. Thus, andrographolide can be developed as a potential therapeutic agent for prostate cancer by inhibition of androgen receptor signaling.

  7. Androgens and obesity.

    Science.gov (United States)

    Allan, Carolyn A; McLachlan, Robert I

    2010-06-01

    As testosterone levels are frequently reduced in obesity, an understanding of the relationship between serum testosterone and adiposity is necessary in the clinical evaluation of these men, in particular when considering testosterone therapy. Population and interventional data suggest a bi-directional relationship exists between testosterone and obesity in men, with lower total testosterone and sex hormone binding globulin (SHBG) (and to a lesser extent free testosterone) levels than their nonobese peers; obesity having an impact at least as important as ageing. Abnormalities in the hypothalamo-pituitary-testicular axis are seen with increasing obesity. Weight loss in massive obesity increases testosterone levels but its role in mild-moderate obesity is unclear. Testosterone supplementation reduces total body fat in hypogonadal and ageing men although the effects on regional fat distribution are less well described. Favourable changes in total body fat and regional fat distribution suggest a potential role for testosterone in obesity. However, lifestyle advice to achieve sustained weight loss should be the mainstay of management. Obese men with confirmed androgen deficiency can be offered treatment, whereas in those with low-normal testosterone levels more research is needed.

  8. Male patients with partial androgen insensitivity syndrome

    DEFF Research Database (Denmark)

    Hellmann, Philip; Christiansen, Peter; Johannsen, Trine Holm

    2012-01-01

    To describe the natural history of phenotype, growth and gonadal function in patients with partial androgen insensitivity syndrome.......To describe the natural history of phenotype, growth and gonadal function in patients with partial androgen insensitivity syndrome....

  9. Creatine supplementation, sleep deprivation, cortisol, melatonin and behavior.

    Science.gov (United States)

    McMorris, T; Harris, R C; Howard, A N; Langridge, G; Hall, B; Corbett, J; Dicks, M; Hodgson, C

    2007-01-30

    The effect of creatine supplementation and sleep deprivation, with intermittent moderate-intensity exercise, on cognitive and psychomotor performance, mood state, effort and salivary concentrations of cortisol and melatonin were examined. Subjects were divided into a creatine supplementation group and a placebo group. They took 5 g of creatine monohydrate or a placebo, dependent on their group, four times a day for 7 days immediately prior to the experiment. They undertook tests examining central executive functioning, short-term memory, choice reaction time, balance, mood state and effort at baseline and following 18-, 24- and 36-h sleep deprivation, with moderate intermittent exercise. Saliva samples were taken prior to each set of tests. A group x time analysis of covariance, with baseline performance the covariate, showed that the creatine group performed significantly (p Cortisol concentrations on Day 1 were significantly (p < 0.01) higher than on Day 2. Mood significantly (p < 0.001) deteriorated up to 24 h with no change from 24 to 36 h. Effort at baseline was significantly (p < 0.01) lower than in the other conditions. It was concluded that, during sleep deprivation with moderate-intensity exercise, creatine supplementation only affects performance of complex central executive tasks.

  10. Intermittent hypoxia and neurorehabilitation.

    Science.gov (United States)

    Gonzalez-Rothi, Elisa J; Lee, Kun-Ze; Dale, Erica A; Reier, Paul J; Mitchell, Gordon S; Fuller, David D

    2015-12-15

    In recent years, it has become clear that brief, repeated presentations of hypoxia [i.e., acute intermittent hypoxia (AIH)] can boost the efficacy of more traditional therapeutic strategies in certain cases of neurologic dysfunction. This hypothesis derives from a series of studies in animal models and human subjects performed over the past 35 yr. In 1980, Millhorn et al. (Millhorn DE, Eldridge FL, Waldrop TG. Respir Physiol 41: 87-103, 1980) showed that electrical stimulation of carotid chemoafferent neurons produced a persistent, serotonin-dependent increase in phrenic motor output that outlasts the stimulus for more than 90 min (i.e., a "respiratory memory"). AIH elicits similar phrenic "long-term facilitation" (LTF) by a mechanism that requires cervical spinal serotonin receptor activation and de novo protein synthesis. From 2003 to present, a series of studies demonstrated that AIH can induce neuroplasticity in the injured spinal cord, causing functional recovery of breathing capacity after cervical spinal injury. Subsequently, it was demonstrated that repeated AIH (rAIH) can induce recovery of limb function, and the functional benefits of rAIH are greatest when paired with task-specific training. Since uncontrolled and/or prolonged intermittent hypoxia can elicit pathophysiology, a challenge of intermittent hypoxia research is to ensure that therapeutic protocols are well below the threshold for pathogenesis. This is possible since many low dose rAIH protocols have induced functional benefits without evidence of pathology. We propose that carefully controlled rAIH is a safe and noninvasive modality that can be paired with other neurorehabilitative strategies including traditional activity-based physical therapy or cell-based therapies such as intraspinal transplantation of neural progenitors. Copyright © 2015 the American Physiological Society.

  11. Fate in intermittent claudication

    DEFF Research Database (Denmark)

    Jelnes, Rolf; Gaardsting, O; Hougaard Jensen, K

    1986-01-01

    113 of the patients (44%) had died. Causes of death were no different from those in the general population. Mortality was twice that of the general population matched for age and sex. Mortality among the men was twice that among the women. In men under 60 mortality was four times that expected......, or an ankle/arm pressure index below 50% were individually significantly associated with progression of the arteriosclerotic disease. These findings show the importance of peripheral blood pressure measurements in the management of patients with intermittent claudication due to arteriosclerotic disease....

  12. Intermittency in Complex Flows

    Science.gov (United States)

    Ben Mahjoub, Otman; Redondo, Jose M.

    2017-04-01

    Experimental results of the complex turbulent wake of a cilinder in 2D [1] and 3D flows [2] were used to investigate the scaling of structure functions, similar research was also performed on wave propagation and breaking in the Ocean [3], in the the stratified Atmosphere (ABL) [4] and in a 100large flume (UPC) for both regular and irregular waves, where long time series of waves propagating and generating breaking turbulence velocity rms and higher order measurements were taken in depth. [3,5] by means of a velocimeter SONTEK3-D. The probability distribution functions of the velocity differences and their non Gaussian distribution related to the energy spectrum indicate that irregularity is an important source of turbulence. From Kolmogorov's K41 and K61 intermittency correction: the p th-order longitudinal velocity structure function δul at scale l in the inertial range of three-dimensional fully developed turbulence is related by ⟨δup⟩ = ⟨(u(x+ l)- u(x))p⟩ ˜ ɛp0/3lp/3 l where ⟨...⟩ represents the spatial average over flow domain, with ɛ0 the mean energy dissipation per unit mass and l is the separation distance. The importance of the random nature of the energy dissipation led to the K62 theory of intermittency, but locality and non-homogeneity are key issues. p p/3 p/3 ξd ⟨δul⟩ ˜ ⟨ɛl ⟩l ˜ l and ξp = p 3 + τp/3 , where now ɛl is a fractal energy dissipation at scale l, τp/3 is the scaling of and ξp is the scaling exponent of the velocity structure function of order p. Both in K41 and K62, the structure functions of third order related to skewness is ξ3 = 1. But this is not true either. We show that scaling exponents ξp do deviate from early studies that only investigated homogeneous turbulence, where a large inertial range dominates. The use of multi-fractal analysis and improvements on Structure function calculations on standard Enhanced mixing is an essential property of turbulence and efforts to alter and to control

  13. Androgens and the ageing male

    DEFF Research Database (Denmark)

    Juul, Anders; Skakkebaek, Niels E

    2002-01-01

    Hypogonadal men share a variety of signs and symptoms such as decreased muscle mass, osteopoenia, increased fat mass, fatigue, decreased libido and cognitive dysfunctions. Controlled trials have demonstrated favourable effects of androgen substitution therapy on these signs and symptoms in men...... with severe primary or secondary hypogonadism. Thus, androgen substitution therapy is warranted in men with true hypogonadism at all ages. Symptoms experienced by otherwise healthy ageing males are non-specific and vague, although some may be similar to symptoms of hypogonadism. Therefore, the term...

  14. Androgen Receptor-Mediated Escape Mechanism from Androgen Ablation Therapy

    Science.gov (United States)

    2008-10-31

    except that no salmon sperm DNA was used as blocking reagent. The immunoprecipitated DNA and un- enriched input DNA were treated with RNase A and purified...A, Wang Y, Suzuki K, Mirosevich J, et al. (2005) Foxa1 and Foxa2 interact with the androgen receptor to regulate prostate and epididymal genes

  15. Unihemispheric sleep deprivation in bottlenose dolphins.

    Science.gov (United States)

    Oleksenko; Mukhametov; Polyakova; Supin; Kovalzon

    1992-03-01

    Unihemispheric and bihemispheric sleep deprivation were performed in bottlenose dolphins. One brain hemisphere was capable of being deprived of delta (0.5-3.0 Hz) sleep in the former condition. Here, an increase in sleep pressure was observed during sleep deprivation in the deprived hemisphere. In the recovery sleep, following unihemispheric sleep deprivation, there was a rebound of delta sleep only in the deprived hemisphere. Following bihemispheric sleep deprivation the animals exhibited an increase in delta sleep in both hemispheres.

  16. Androgens and the ageing male

    DEFF Research Database (Denmark)

    Juul, Anders; Skakkebaek, Niels E

    2002-01-01

    not have an andropause. As large placebo-controlled studies of androgen treatment in elderly males are lacking, proper risk assessment of adverse effects such as prostate cancer following testosterone treatment in elderly males is completely lacking. In the future, testosterone therapy may prove beneficial...

  17. Androgenic switch in barley microspores

    NARCIS (Netherlands)

    de Faria Maraschin, Simone

    2005-01-01

    Barley androgenesis represents an attractive system to study stress-induced cell differentiation and is a valuable tool for efficient plant breeding. The switch from the pollen developmental pathway towards an androgenic route involves several well-described morphological changes. However, little is

  18. Metabolic Effects of Intermittent Fasting.

    Science.gov (United States)

    Patterson, Ruth E; Sears, Dorothy D

    2017-08-21

    The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved health outcomes. A MEDLINE search was performed using PubMed and the terms "intermittent fasting," "fasting," "time-restricted feeding," and "food timing." Modified fasting regimens appear to promote weight loss and may improve metabolic health. Several lines of evidence also support the hypothesis that eating patterns that reduce or eliminate nighttime eating and prolong nightly fasting intervals may result in sustained improvements in human health. Intermittent fasting regimens are hypothesized to influence metabolic regulation via effects on (a) circadian biology, (b) the gut microbiome, and (c) modifiable lifestyle behaviors, such as sleep. If proven to be efficacious, these eating regimens offer promising nonpharmacological approaches to improving health at the population level, with multiple public health benefits.

  19. Intermittent 96-Hour Auricular Electroacupuncture for Hot Flashes in Patients with Prostate Cancer: A Pilot Study.

    Science.gov (United States)

    Rich, Tyvin; Porter, Gerald W; Ricks-Santi, Luisel; Milshtein, Tzvi; Corbin, Thomas

    2017-10-01

    Objective: The hot flash is a common vasomotor disorder that causes distress in menopausal women and that can be debilitating in men with prostate cancer who are treated with androgen deprivation therapy (ADT). The utility of auricular electroacupuncture (AEA) was tested exclusively for a small cohort of men with ADT-induced vasomotor symptoms while the men underwent a course of curative radiotherapy. Materials and Methods: Prior to and during radiotherapy treatment, men with vasomotor symptoms were given repeated questionnaires regarding severity and frequency of hot flashes, quality of life (QoL), and sleep over a 6-week span of an AEA protocol. Each subject's heart rate variability (HRV) was obtained repeatedly every week in an ambulatory setting with a BlueCardio device (BlueCardio, Miami, FL). The AEA intervention was given with a Neurova device (Nunka Corporation, CM Wellness Clinic, Pompano Beach, FL) that used three needles at Master points Sympathetic, Shen Men , and Point Zero, which were located precisely with a bipolar point finder. Intermittent microcurrent stimulation was given every other week for 96 hours, using a cyclic programmed output of 2 hours on and 2 hours off. Results: Of 10 men completing the 6-week protocol, all responded with significantly lower frequency, duration, and severity of vasomotor symptoms; QoL and sleep scores improved significantly. The HRV analysis showed significantly lower low-frequency/high-frequency power ratios in each individual, compared to baseline, that were consistent with the subjective responses. Conclusions: Vasomotor disturbance, caused by gender hormone withdrawal-either naturally or in patients treated with ADT, as in this study-is a well-defined neurophysiologic condition. This disorder is a constellation of findings that reflect autonomic disturbances of excessive sympathetic and reduced parasympathetic activity. AEA intervention with the Neurova device is simple to administer, is well-tolerated, and

  20. Intermittent 96-Hour Auricular Electroacupuncture for Hot Flashes in Patients with Prostate Cancer: A Pilot Study

    Science.gov (United States)

    Porter, Gerald W.; Ricks-Santi, Luisel; Milshtein, Tzvi; Corbin, Thomas

    2017-01-01

    Abstract Objective: The hot flash is a common vasomotor disorder that causes distress in menopausal women and that can be debilitating in men with prostate cancer who are treated with androgen deprivation therapy (ADT). The utility of auricular electroacupuncture (AEA) was tested exclusively for a small cohort of men with ADT-induced vasomotor symptoms while the men underwent a course of curative radiotherapy. Materials and Methods: Prior to and during radiotherapy treatment, men with vasomotor symptoms were given repeated questionnaires regarding severity and frequency of hot flashes, quality of life (QoL), and sleep over a 6-week span of an AEA protocol. Each subject's heart rate variability (HRV) was obtained repeatedly every week in an ambulatory setting with a BlueCardio device (BlueCardio, Miami, FL). The AEA intervention was given with a Neurova device (Nunka Corporation, CM Wellness Clinic, Pompano Beach, FL) that used three needles at Master points Sympathetic, Shen Men, and Point Zero, which were located precisely with a bipolar point finder. Intermittent microcurrent stimulation was given every other week for 96 hours, using a cyclic programmed output of 2 hours on and 2 hours off. Results: Of 10 men completing the 6-week protocol, all responded with significantly lower frequency, duration, and severity of vasomotor symptoms; QoL and sleep scores improved significantly. The HRV analysis showed significantly lower low-frequency/high-frequency power ratios in each individual, compared to baseline, that were consistent with the subjective responses. Conclusions: Vasomotor disturbance, caused by gender hormone withdrawal—either naturally or in patients treated with ADT, as in this study—is a well-defined neurophysiologic condition. This disorder is a constellation of findings that reflect autonomic disturbances of excessive sympathetic and reduced parasympathetic activity. AEA intervention with the Neurova device is simple to administer, is well

  1. Can exercise ameliorate treatment toxicity during the initial phase of testosterone deprivation in prostate cancer patients? Is this more effective than delayed rehabilitation?

    Directory of Open Access Journals (Sweden)

    Newton Robert U

    2012-09-01

    Full Text Available Abstract Background There has been substantial increase in use of androgen deprivation therapy as adjuvant management of prostate cancer. However, this leads to a range of musculoskeletal toxicities including reduced bone mass and increased skeletal fractures compounded with rapid metabolic alterations, including increased body fat, reduced lean mass, insulin resistance and negative lipoprotein profile, increased incidence of cardiovascular and metabolic morbidity, greater distress and reduced quality of life. Numerous research studies have demonstrated certain exercise prescriptions to be effective at preventing or even reversing these treatment toxicities. However, all interventions to date have been of rehabilitative intent being implemented after a minimum of 3 months since initiation of androgen deprivation, by which time considerable physical and psychological health problems have manifested. The pressing question is whether it is more efficacious to commence exercise therapy at the same time as initiating androgen deprivation, so treatment induced adverse effects can be immediately attenuated or indeed prevented. Methods/design We are proposing a multi-site randomized controlled trial with partial crossover to examine the effects of timing of exercise implementation (immediate or delayed on preserving long-term skeletal health, reversing short- and long-term metabolic and cardiovascular risk factors, and supporting mental health in men receiving androgen deprivation therapy. 124 men who are about to initiate androgen deprivation for prostate cancer will be randomized to immediate or delayed groups. Immediate will commence a 6-month exercise program within 7–10 days of their first dose. Delayed will receive usual care for 6 months and then commence the exercise program for 6 months (partial cross-over. Immediate will be free to adopt the lifestyle of their choosing following the initial 6-month intervention. Measurements for primary and

  2. Can exercise ameliorate treatment toxicity during the initial phase of testosterone deprivation in prostate cancer patients? Is this more effective than delayed rehabilitation?

    International Nuclear Information System (INIS)

    Newton, Robert U; Taaffe, Dennis R; Spry, Nigel; Cormie, Prue; Chambers, Suzanne K; Gardiner, Robert A; Shum, David HK; Joseph, David; Galvão, Daniel A

    2012-01-01

    There has been substantial increase in use of androgen deprivation therapy as adjuvant management of prostate cancer. However, this leads to a range of musculoskeletal toxicities including reduced bone mass and increased skeletal fractures compounded with rapid metabolic alterations, including increased body fat, reduced lean mass, insulin resistance and negative lipoprotein profile, increased incidence of cardiovascular and metabolic morbidity, greater distress and reduced quality of life. Numerous research studies have demonstrated certain exercise prescriptions to be effective at preventing or even reversing these treatment toxicities. However, all interventions to date have been of rehabilitative intent being implemented after a minimum of 3 months since initiation of androgen deprivation, by which time considerable physical and psychological health problems have manifested. The pressing question is whether it is more efficacious to commence exercise therapy at the same time as initiating androgen deprivation, so treatment induced adverse effects can be immediately attenuated or indeed prevented. We are proposing a multi-site randomized controlled trial with partial crossover to examine the effects of timing of exercise implementation (immediate or delayed) on preserving long-term skeletal health, reversing short- and long-term metabolic and cardiovascular risk factors, and supporting mental health in men receiving androgen deprivation therapy. 124 men who are about to initiate androgen deprivation for prostate cancer will be randomized to immediate or delayed groups. Immediate will commence a 6-month exercise program within 7–10 days of their first dose. Delayed will receive usual care for 6 months and then commence the exercise program for 6 months (partial cross-over). Immediate will be free to adopt the lifestyle of their choosing following the initial 6-month intervention. Measurements for primary and secondary endpoints will take place at baseline, 6

  3. Consequences of sleep deprivation.

    Science.gov (United States)

    Orzeł-Gryglewska, Jolanta

    2010-01-01

    This paper presents the history of research and the results of recent studies on the effects of sleep deprivation in animals and humans. Humans can bear several days of continuous sleeplessness, experiencing deterioration in wellbeing and effectiveness; however, also a shorter reduction in the sleep time may lead to deteriorated functioning. Sleeplessness accounts for impaired perception, difficulties in keeping concentration, vision disturbances, slower reactions, as well as the appearance of microepisodes of sleep during wakefulness which lead to lower capabilities and efficiency of task performance and to increased number of errors. Sleep deprivation results in poor memorizing, schematic thinking, which yields wrong decisions, and emotional disturbances such as deteriorated interpersonal responses and increased aggressiveness. The symptoms are accompanied by brain tissue hypometabolism, particularly in the thalamus, prefrontal, frontal and occipital cortex and motor speech centres. Sleep deficiency intensifies muscle tonus and coexisting tremor, speech performance becomes monotonous and unclear, and sensitivity to pain is higher. Sleeplessness also relates to the changes in the immune response and the pattern of hormonal secretion, of the growth hormone in particular. The risk of obesity, diabetes and cardiovascular disease increases. The impairment of performance which is caused by 20-25 hours of sleeplessness is comparable to that after ethanol intoxication at the level of 0.10% blood alcohol concentration. The consequences of chronic sleep reduction or a shallow sleep repeated for several days tend to accumulate and resemble the effects of acute sleep deprivation lasting several dozen hours. At work, such effects hinder proper performance of many essential tasks and in extreme situations (machine operation or vehicle driving), sleep loss may be hazardous to the worker and his/her environment.

  4. Androgen Depletion Induces Senescence in Prostate Cancer Cells through Down-regulation of Skp2

    Directory of Open Access Journals (Sweden)

    Zuzana Pernicová

    2011-06-01

    Full Text Available Although the induction of senescence in cancer cells is a potent mechanism of tumor suppression, senescent cells remain metabolically active and may secrete a broad spectrum of factors that promote tumorigenicity in neighboring malignant cells. Here we show that androgen deprivation therapy (ADT, a widely used treatment for advanced prostate cancer, induces a senescence-associated secretory phenotype in prostate cancer epithelial cells, indicated by increases in senescence-associated β-galactosidase activity, heterochromatin protein 1β foci, and expression of cathepsin B and insulin-like growth factor binding protein 3. Interestingly, ADT also induced high levels of vimentin expression in prostate cancer cell lines in vitro and in human prostate tumors in vivo. The induction of the senescence-associated secretory phenotype by androgen depletion was mediated, at least in part, by down-regulation of S-phase kinase-associated protein 2, whereas the neuroendocrine differentiation of prostate cancer cells was under separate control. These data demonstrate a previously unrecognized link between inhibition of androgen receptor signaling, down-regulation of S-phase kinase-associated protein 2, and the appearance of secretory, tumor-promoting senescent cells in prostate tumors. We propose that ADT may contribute to the development of androgen-independent prostate cancer through modulation of the tissue microenvironment by senescent cells.

  5. Sleep Deprivation and Advice Taking

    NARCIS (Netherlands)

    Hausser, J.A.; Leder, J.; Ketturat, C.; Dresler, M.; Faber, N.S.

    2016-01-01

    Judgements and decisions in many political, economic or medical contexts are often made while sleep deprived. Furthermore, in such contexts individuals are required to integrate information provided by - more or less qualified - advisors. We asked if sleep deprivation affects advice taking. We

  6. Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs)

    OpenAIRE

    Gao, Wenqing; Dalton, James T.

    2007-01-01

    Selective androgen receptor modulators (SARMs) are a novel class of androgen receptor (AR) ligands that might change the future of androgen therapy dramatically. With improved pharmacokinetic characteristics and tissue-selective pharmacological activities, SARMs are expected to greatly extend the clinical applications of androgens to osteoporosis, muscle wasting, male contraception and diseases of the prostate. Mechanistic studies with currently available SARMs will help to define the contrib...

  7. Salivary Duct Carcinoma: An Update on Morphologic Mimics and Diagnostic Use of Androgen Receptor Immunohistochemistry.

    Science.gov (United States)

    Udager, Aaron M; Chiosea, Simion I

    2017-09-01

    More than 15 years ago, seminal studies by Dr. E. Leon Barnes and colleagues transformed our understanding of salivary duct carcinoma (SDC) and, in doing so, paved the way for contemporary diagnostic and therapeutic approaches to this aggressive salivary adenocarcinoma. In particular, attention to the apocrine phenotype of SDC and expression of androgen receptor (AR) by immunohistochemistry has improved the diagnostic accuracy and showed how SDC can be reliably distinguished from its morphologic mimics (i.e., other salivary gland carcinomas with high grade transformation, low grade cribriform cystadenocarcinoma, and squamous cell carcinomas involving parotid). Furthermore, the observation that SDC shares AR expression with prostate cancer and apocrine breast cancer foresaw the discovery of common molecular alterations between SDC and these tumor types and draw attention to androgen deprivation therapy for SDC patients.

  8. Differential Mechanisms of Androgen Resistance

    Science.gov (United States)

    2007-12-01

    two infertile Finnish men. Fertility and Sterility , 79, Supple3, 2003. Miyake H, Hara I, Eto H.2005 Clinical outcome of maximum androgen blockade...identified in two infertile men (Lund et al 2003). It can be postulated that Q58L could change the conformation of the polyglutamide tract thereby...and PC3- LNCAP AR (C) tumour xenografts. 3 million cells in sterile PBS (1:1 ratio with Matrigel) were implanted s.c. into the flank of SCID mice

  9. Intermedia and Intermittency

    Directory of Open Access Journals (Sweden)

    Veres Bálint

    2014-12-01

    Full Text Available It is commonly known that medial reflections have been initiated by attempts to secure the borders of discrete medial forms and to define the modus operandi of each essentialized medial area. Later on, the focus of study has shifted to plurimedial formations and the interactions between predefined medial genres. In the last few decades, taxonomic approaches to various multi-, inter-, and transmedial phenomena dominated the discussions, which offered invaluable support in mapping the terrain, but at the same time hindered the analysis of the ephemeral, time-dependent aspects of plurimedial operations. While we explore the properties of each medial configuration, we lose sight of the actual historical drivers that produce ever-new configurations. My thesis is that any discourse on intermediality should be paralleled by a discourse on cultural intermittency, and consequently, media studies should involve an approach that focuses on the “ecosystem” of the constantly renewing media configurations from the point of view of their vitalizing potential and capability to trigger heightened experiences. This approach draws much inspiration from K. Ludwig Pfeiffer’s media anthropology that gives orientation in my paper.

  10. Coho salmon dependence on intermittent streams.

    Science.gov (United States)

    P.J. Wigington; J.L. Ebersole; M.E. Colvin; S.G. Leibowitz; B. Miller; B. Hansen; H. Lavigne; D. White; J.P. Baker; M.R. Church; J.R. Brooks; M.A. Cairns; J.E. Compton

    2006-01-01

    In this paper, we quantify the contributions of intermittent streams to coho salmon production in an Oregon coastal watershed. We provide estimates of (1) proportion of spawning that occurred in intermittent streams, (2) movement of juveniles into intermittent streams, (3) juvenile survival in intermittent and perennial streams during winter, and (4) relative size of...

  11. Sleep deprivation in depression.

    Science.gov (United States)

    Hemmeter, Ulrich-Michael; Hemmeter-Spernal, Julia; Krieg, Jürgen-Christian

    2010-07-01

    Sleep deprivation (SD) is a powerful antidepressant treatment that shows antidepressant responses within hours in 40-60% of depressed patients. In more than 80% of responders to SD, a relapse into depression occurred after the recovery night. In addition, it serves as an excellent tool to examine the neurobiological disturbance of depression and may profoundly contribute to the development of new specific and more rapidly acting antidepressants. The reason why SD works and relapses occur is still unclear. A key to solve this problem is to include the current knowledge about the neurobiological disturbance of depression in research, with a focus on neurobiological aspects of sleep and SD (sleep EEG, neuroendocrinology, neurochemistry and chronobiology). Based on findings from these different areas, different strategies to stabilize the antidepressant effect of SD have been applied. This article provides an overview of clinical and neurobiological responses related to SD in depression.

  12. New insights into the androgen biotransformation in prostate cancer: A regulatory network among androgen, androgen receptors and UGTs.

    Science.gov (United States)

    Qin, Xuan; Liu, Mingyao; Wang, Xin

    2016-04-01

    Androgen, as one kind of steroid hormones, is pivotal in the hormone-sensitive cancer, such as prostate cancer (PCa). The synthesis, elimination, and bioavailability of androgen in prostate cells have been proved to be a main cause of the carcinogenesis, maintenance and deterioration of PCa. This review illustrates the outlines of androgen biotransformation, and further discusses the different enzymes, especially UDP-glucuronyltransferases (UGTs) embedded in both benign and malignant prostate cells, which catalyze the reactions. Although many inhibitors of the enzymes responsible for the synthesis of androgens have been developed into drugs to fight against PCa, the elimination procedures metabolized by the UGTs are less emphasized. Thus the regulatory network among androgen, androgen receptors (AR) and UGTs is carefully reviewed in this article, indicating the determinant effects of UGTs on prostatic androgens and the regulation of AR. Finally, the hypothesis is also put forward that the regulators of UGTs may be developed to accelerate the androgen elimination and benefit PCa therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Identifying a deprivation of liberty.

    Science.gov (United States)

    Griffith, Richard

    2016-01-01

    The UK Supreme Court's judgment in Cheshire West and Chester Council v P [2014] fundamentally changed the approach to determining if a person who lacked capacity was deprived of their liberty by the State. The Supreme Court further held that a deprivation of liberty could occur in any care setting including a person's own home. In this article, Richard Griffith discusses the approach district nurses should adopt when determining whether a patient being cared for at home is deprived of his/her liberty.

  14. Molecular mechanisms of androgen receptor functions

    NARCIS (Netherlands)

    K. Steketee (Karine)

    2007-01-01

    textabstractThe androgens testosterone (T) and dihydrotestosterone (DHT) are steroid hormones, which are necessary for development and maintenance of the functions of the male sex organs, including the prostate. Androgens also play an important role in benign abnormalities of the prostate and in the

  15. Androgen receptors and experimental bone loss - an in vivo and in vitro study.

    Science.gov (United States)

    Steffens, Joao Paulo; Coimbra, Leila Santana; Rossa, Carlos; Kantarci, Alpdogan; Van Dyke, Thomas E; Spolidorio, Luis Carlos

    2015-12-01

    Testosterone is a sex hormone that exhibits many functions beyond reproduction; one such function is the regulation of bone metabolism. The role played by androgen receptors during testosterone-mediated biological processes associated with bone metabolism is largely unknown. This study aims to use a periodontal disease model in vivo in order to assess the involvement of androgen receptors on microbial-induced inflammation and alveolar bone resorption in experimental bone loss. The impact of hormone deprivation was tested through both orchiectomy and chemical blockage of androgen receptor using flutamide (FLU). Additionally, the direct effect of exogenous testosterone, and the role of the androgen receptor, on osteoclastogenesis were investigated. Thirty male adult rats (n=10/group) were subjected to: 1-orchiectomy (OCX); 2-OCX sham surgery; or 3-OCX sham surgery plus FLU, four weeks before the induction of experimental bone loss. Ten OCX sham-operated rats were not subjected to experimental bone loss and served as healthy controls. The rats were euthanized two weeks later, so as to assess bone resorption and the production of inflammatory cytokines in the gingival tissue and serum. In order to study the in vitro impact of testosterone, osteoclasts were differentiated from RAW264.7 cells and testosterone was added at increasing concentrations. Both OCX and FLU increased bone resorption, but OCX alone was observed to increase osteoclast count. IL-1β production was increased only in the gingival tissue of OCX animals, whereas FLU-treated animals presented a decreased expression of IL-6. Testosterone reduced the osteoclast formation in a dose-dependent manner, and significantly impacted the production of TNF-α; FLU partially reversed these actions. When taken together, our results indicate that testosterone modulates experimental bone loss, and that this action is mediated, at least in part, via the androgen receptor. Copyright © 2015 Elsevier Inc. All rights

  16. Androgens, body fat Distribution and Adipogenesis.

    Science.gov (United States)

    Zerradi, Mouna; Dereumetz, Julie; Boulet, Marie-Michèle; Tchernof, André

    2014-12-01

    Androgens are regulators of important adipocyte functions such as adipogenesis, lipid storage, and lipolysis. Through depot-specific impact on the cells of each fat compartment, androgens could modulate body fat distribution patterns in humans. Testosterone and dihydrotestosterone have been shown to inhibit the differentiation of preadipocytes to lipid-storing adipocytes in several models including primary cultures of human adipocytes from both men and women. Androgen effects have also been observed on some markers of lipid metabolism such as LPL activity, fatty acid uptake, and lipolysis. Possible depot-specific and sex-specific effects have been observed in some but not all models. Transformation of androgen precursors to active androgens or their inactivation by enzymes that are expressed and functional in adipose tissue may contribute to modulate the local availability of active hormones. These phenomena, along with putative depot-specific interactions with glucocorticoids may contribute to human body fat distribution patterns.

  17. Neurobiological Consequences of Sleep Deprivation

    Science.gov (United States)

    Alkadhi, Karim; Zagaar, Munder; Alhaider, Ibrahim; Salim, Samina; Aleisa, Abdulaziz

    2013-01-01

    Although the physiological function of sleep is not completely understood, it is well documented that it contributes significantly to the process of learning and memory. Ample evidence suggests that adequate sleep is essential for fostering connections among neuronal networks for memory consolidation in the hippocampus. Sleep deprivation studies are extremely valuable in understanding why we sleep and what are the consequences of sleep loss. Experimental sleep deprivation in animals allows us to gain insight into the mechanism of sleep at levels not possible to study in human subjects. Many useful approaches have been utilized to evaluate the effect of sleep loss on cognitive function, each with relative advantages and disadvantages. In this review we discuss sleep and the detrimental effects of sleep deprivation mostly in experimental animals. The negative effects of sleep deprivation on various aspects of brain function including learning and memory, synaptic plasticity and the state of cognition-related signaling molecules are discussed. PMID:24179461

  18. Neurobiological Consequences of Sleep Deprivation

    OpenAIRE

    Alkadhi, Karim; Zagaar, Munder; Alhaider, Ibrahim; Salim, Samina; Aleisa, Abdulaziz

    2013-01-01

    Although the physiological function of sleep is not completely understood, it is well documented that it contributes significantly to the process of learning and memory. Ample evidence suggests that adequate sleep is essential for fostering connections among neuronal networks for memory consolidation in the hippocampus. Sleep deprivation studies are extremely valuable in understanding why we sleep and what are the consequences of sleep loss. Experimental sleep deprivation in animals allows us...

  19. Sleep Deprivation and Neurobehavioral Dynamics

    OpenAIRE

    Basner, Mathias; Rao, Hengyi; Goel, Namni; Dinges, David F.

    2013-01-01

    Lifestyles involving sleep deprivation are common, despite mounting evidence that both acute total sleep deprivation and chronically restricted sleep degrade neurobehavioral functions associated with arousal, attention, memory and state stability. Current research suggests dynamic differences in the way the central nervous system responds to acute versus chronic sleep restriction, which is reflected in new models of sleep-wake regulation. Chronic sleep restriction likely induces long-term neu...

  20. Health Effects of Sleep Deprivation,

    Science.gov (United States)

    1990-06-01

    sleep -deprived subjects, they often observed frequent, but transient, psychotic behavior.32 These behavioral pathologies are easily missed because of...physical harm, sleep deprivation is also believed to result in mental harm, i.e., psychosis or intensification of psycho- pathology . 319 The belief that...Process. Glenview, IL, Scott, Foresman, 1973, pp 48-58. 80. Dement WC: The relevance of sleep pathologies to the function of sleep . In Drucker-Colin R

  1. ErbB-2 signaling plays a critical role in regulating androgen-sensitive and castration-resistant androgen receptor-positive prostate cancer cells.

    Science.gov (United States)

    Muniyan, Sakthivel; Chen, Siu-Ju; Lin, Fen-Fen; Wang, Zhengzhong; Mehta, Parmender P; Batra, Surinder K; Lin, Ming-Fong

    2015-11-01

    While androgen deprivation therapy (ADT) reduces tumor burden, autocrine growth factor loops such as human epidermal growth factor receptor 2 (HER2/ErbB-2/neu) have been proposed to contribute to prostate cancer (PCa) survival and relapse. However, the role of ErbB-2 in regulating androgen-sensitive (AS) and castration-resistant (CR) cell proliferation remains unclear. Here, we determined the role of ErbB-2 in PCa progression and survival under steroid-reduced conditions using two independent PCa cell progression models. In AR-positive androgen-independent (AI) PCa cells that exhibit the CR phenotype, ErbB-2 was constitutively activated, compared to corresponding AS PCa cells. In AS LNCaP C-33 cells, androgen-induced ErbB-2 activation through ERK1/2 mediates PCa cell proliferation. Further, the ErbB-2-specific but not EGFR-specific inhibitor suppresses basal and androgen-stimulated cell proliferation and also blocks ERK1/2 activation. ErbB-2 ectopic expression and cPAcP siRNA transfection of LNCaP C-33 cells each increases ErbB-2 tyrosine phosphorylation, correlating with increased AI PSA secretion and cell proliferation. Conversely, trapping ErbB-2 by transfected endoplasmic reticulum-targeting ScFv5R expression vector abolished DHT-induced LNCaP C-33 cell growth. Moreover, inhibition of ErbB-2 but not EGFR in AI LNCaP C-81 and MDA PCa2b-AI PCa cells significantly abolished AI cell growth. In contrast to androgens via ErbB-2/ERK1/2 signaling in AS PCa cells, the inhibition of ErbB-2 abrogated AI cell proliferation by inhibiting the cell survival protein Akt in those AI cells. These results suggest that ErbB-2 is a prominent player in mediating the ligand-dependent and -independent activation of AR in AS and AI/CR PCa cells respectively for PCa progression and survival. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Enhanced radiosensitization of enzalutamide via schedule dependent administration to androgen-sensitive prostate cancer cells.

    Science.gov (United States)

    Ghashghaei, Maryam; Paliouras, Miltiadis; Heravi, Mitra; Bekerat, Hamed; Trifiro, Mark; Niazi, Tamim M; Muanza, Thierry

    2018-01-01

    Prostate cancer (PCa) is a progressive disease and the most diagnosed cancer in men. The current standard of care for high-risk localized PCa is a combination of androgen deprivation therapy (ADT) and radiation (XRT). The majority of these patients however become resistant due to incomplete responses to ADT as a result of selective cells maintaining androgen receptor (AR) activity. Improvement can be made if increasing radiosensitivity is realized. Therefore, the aim of this study is to investigate the efficacy of the next-generation PCa drug Enzalutamide (ENZA), as a radiosensitizer in XRT therapy. Using a number of androgen-dependent (LNCaP, PC3-T877A) and androgen-independent (C4-2, 22RV1, PC3, PC3-AR V7) cell lines, the effect of ENZA as a radiosensitizer was studied alone or in combination with ADT and/or XRT. Cell viability and cell survival were assessed, along with determination of cell cycle arrest, DNA damage response and repair, apoptosis and senescence. Our results indicated that either ENZA alone (in AR positive, androgen-dependent PCa cells) or in combination with ADT (in AR positive, hormone-insensitive PCa cells) potentiates radiation response [Dose enhancement factor (DEF) of 1.75 in LNCAP and 1.35 in C4-2] stronger than ADT + XRT conditions. Additionally, ENZA sensitized androgen dependent PCa cells to XRT in a schedule-dependent manner, where concurrent administration of ENZA and radiation lead to a maximal radiosensitization when compared to either drug administration prior or after XRT. In LNCaP cells, ENZA treatment significantly prolonged the presence of XRT-induced phospho-γH2AX up to 24 h after treatment; suggesting enhanced DNA damage. It also significantly increased XRT-induced apoptosis and senescence. Our data indicates that ENZA acts as a much stronger radiosensitizer compared to ADT. We have also observed that its efficacy is schedule dependent and related to increased levels of DNA damage and a delay of DNA repair processes

  3. Androgen receptor expression in human ovarian and uterine tissue of long term androgen-treated transsexual women

    NARCIS (Netherlands)

    D. Chadha; T.D. Pache; F.J. Huikeshoven (Frans); A.O. Brinkmann (Albert); Th.H. van der Kwast (Theo)

    1994-01-01

    textabstractAndrogen receptor (AR) modulation in human uteri and ovaries of long term androgen-treated transsexual female patients was investigated. Androgen receptor expression was evaluated immunohistochemically in the ovaries of 11 and the endometria and myometria of six androgen-treated

  4. Structural characteristics of anabolic androgenic steroids contributing to binding to the androgen receptor and to their anabolic and androgenic activities. Applied modifications in the steroidal structure.

    Science.gov (United States)

    Fragkaki, A G; Angelis, Y S; Koupparis, M; Tsantili-Kakoulidou, A; Kokotos, G; Georgakopoulos, C

    2009-02-01

    Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone introduced for therapeutic purposes providing enhanced anabolic potency with reduced androgenic effects. Androgens mediate their action through their binding to the androgen receptor (AR) which is mainly expressed in androgen target tissues, such as the prostate, skeletal muscle, liver and central nervous system. This paper reviews some of the wide spectrum of testosterone and synthetic AAS structure modifications related to the intended enhancement in anabolic activity. The structural features of steroids necessary for effective binding to the AR and those which contribute to the stipulation of the androgenic and anabolic activities are also presented.

  5. The Effect of Intermittent Feeding on Metabolic Signs of Chronic Stress in Male NMRI Mice

    Directory of Open Access Journals (Sweden)

    Fatemeh Sadat Hoseini Namvar

    2016-03-01

    Full Text Available Background and Objectives: Reduction of calorie (energy intake can lead to stress management and improvement of nervous system function. In this research, the effect of intermittent feeding on metabolic signs of stress was investigated. Methods: Male laboratory mice with mean weight of 27±3g were divided into 4 groups of 7 each. The control group received ad-lib food and water and did not have stress. The second group (experimental was deprived from food 2 hours per day for one week, and then went under stress for 4 days. The third group was only deprived from food 2 hours per day for a week, and the fourth group received electric shock for 4 days without food deprivation. In this investigation, plasma corticosterone level, the amount of food consumption, delay in eating, weight gain, and the amount of feces, were measured. Data were analyzed using one-way ANOVA and Tukey test. The significance level was considered p<0.5. Results: In this study, stress increased the plasma level of corticosterone and fecal materials, and reduced food intake and weight of the animals and increased delay in eating. In the stress with intermittent feeding group, plasma level of corticosterone and delay in eating increased, and food intake and feces decreased. In this group, weight change was not observed, but in animals that only had intermittent feeding, increase in weight and food intake was observed. Also, delay in eating was decreased. Conclusion: The results of this study indicated that intermittent feeding can influence the effect of stress on nutrition and metabolism.

  6. Androgen ablation augments human HLA2.1-restricted T cell responses to PSA self-antigen in transgenic mice.

    Science.gov (United States)

    Arredouani, Mohamed S; Tseng-Rogenski, Stephanie S; Hollenbeck, Brent K; Escara-Wilke, June; Leander, Karen R; Defeo-Jones, Deborah; Hwang, Clara; Sanda, Martin G

    2010-06-15

    In recent years, there has been an increasing interest in targeting human prostate tumor-associated antigens (TAAs) for prostate cancer immunotherapy as an alternative to other therapeutic modalities. However, immunologic tolerance to TAA poses a significant obstacle to effective, TAA-targeted immunotherapy. We sought to investigate whether androgen deprivation would result in circumventing immune tolerance to prostate TAA by impacting CD8 cell responses. To this end, we generated a transgenic mouse that expresses the human prostate-specific antigen (PSA) specifically in the prostate, and crossed it to the HLA-A2.1 transgenic mouse to evaluate how androgen deprivation affects human HLA A2.1-resticted T cell responses following immunization of PSA-expressing mice by vaccinia-PSA (PROSTVAC). Our PSA transgenic mouse showed restricted expression of PSA in the prostate and detectable circulating PSA levels. Additionally, PSA expression was androgen-dependent with reduced PSA expression in the prostate within 1 week of castration, and undetectable PSA by day 42 after castration as evaluated by ELISA. Castration of the PSA/A2.1 hybrid mouse prior to immunization with a PSA-expressing recombinant vaccinia virus resulted in a significant augmentation of PSA-specific cytotoxic lymphocytes. This humanized hybrid mouse model provides a well-defined system to gain additional insight into the mechanisms of immune tolerance to PSA and to test novel strategies aiming at circumventing immune tolerance to PSA and other TAA for targeted prostate cancer immunotherapy.

  7. Intermittent fasting attenuates inflammasome activity in ischemic stroke.

    Science.gov (United States)

    Fann, David Yang-Wei; Santro, Tomislav; Manzanero, Silvia; Widiapradja, Alexander; Cheng, Yi-Lin; Lee, Seung-Yoon; Chunduri, Prasad; Jo, Dong-Gyu; Stranahan, Alexis M; Mattson, Mark P; Arumugam, Thiruma V

    2014-07-01

    Recent findings have revealed a novel inflammatory mechanism that contributes to tissue injury in cerebral ischemia mediated by multi-protein complexes termed inflammasomes. Intermittent fasting (IF) can decrease the levels of pro-inflammatory cytokines in the periphery and brain. Here we investigated the impact of IF (16h of food deprivation daily) for 4months on NLRP1 and NLRP3 inflammasome activities following cerebral ischemia. Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion (I/R). IF decreased the activation of NF-κB and MAPK signaling pathways, the expression of NLRP1 and NLRP3 inflammasome proteins, and both IL-1β and IL-18 in the ischemic brain tissue. These findings demonstrate that IF can attenuate the inflammatory response and tissue damage following ischemic stroke by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Sprint cycling training improves intermittent run performance

    Directory of Open Access Journals (Sweden)

    Hardaway Chun-Kwan Chan

    2018-01-01

    Conclusions: Sprint cycling significantly improved intermittent run performance, VO2max and peak power output at VO2max. Sprint cycling training is suitable for intermittent sports athletes but separate speed and COD training should be included.

  9. Androgens in pregnancy: roles in parturition.

    Science.gov (United States)

    Makieva, Sofia; Saunders, Philippa T K; Norman, Jane E

    2014-01-01

    Understanding the physiology of pregnancy enables effective management of pregnancy complications that could otherwise be life threatening for both mother and fetus. A functional uterus (i) retains the fetus in utero during pregnancy without initiating stretch-induced contractions and (ii) is able to dilate the cervix and contract the myometrium at term to deliver the fetus. The onset of labour is associated with successful cervical remodelling and contraction of myometrium, arising from concomitant activation of uterine immune and endocrine systems. A large body of evidence suggests that actions of local steroid hormones may drive changes occurring in the uterine microenvironment at term. Although there have been a number of studies considering the potential role(s) played by progesterone and estrogen at the time of parturition, the bio-availability and effects of androgens during pregnancy have received less scrutiny. The aim of this review is to highlight potential roles of androgens in the biology of pregnancy and parturition. A review of published literature was performed to address (i) androgen concentrations, including biosynthesis and clearance, in maternal and fetal compartments throughout gestation, (ii) associations of androgen concentrations with adverse pregnancy outcomes, (iii) the role of androgens in the physiology of cervical remodelling and finally (iv) the role of androgens in the physiology of myometrial function including any impact on contractility. Some, but not all, androgens increase throughout gestation in maternal circulation. The effects of this increase are not fully understood; however, evidence suggests that increased androgens might regulate key processes during pregnancy and parturition. For example, androgens are believed to be critical for cervical remodelling at term, in particular cervical ripening, via regulation of cervical collagen fibril organization. Additionally, a number of studies highlight potential roles for androgens

  10. Androgen effects on women's gendered behaviour.

    Science.gov (United States)

    Udry, J R; Morris, N M; Kovenock, J

    1995-07-01

    Test of the applicability of the hormonal theory of sex-dimorphic behaviour to adult women is achieved in this study by assembling measures of prenatal and adult androgen exposure, and a broad measure of gendered behaviour on a sample of white women aged 27-30. Androgen exposure in the second (and no other) trimester of fetal life, combined with and in interaction with adult androgens, masculineses women's behaviour and explains a substantial proportion of the within-sex variance in women's adult gendered behaviour.

  11. Intermittent control of coexisting attractors.

    Science.gov (United States)

    Liu, Yang; Wiercigroch, Marian; Ing, James; Pavlovskaia, Ekaterina

    2013-06-28

    This paper proposes a new control method applicable for a class of non-autonomous dynamical systems that naturally exhibit coexisting attractors. The central idea is based on knowledge of a system's basins of attraction, with control actions being applied intermittently in the time domain when the actual trajectory satisfies a proximity constraint with regards to the desired trajectory. This intermittent control uses an impulsive force to perturb one of the system attractors in order to switch the system response onto another attractor. This is carried out by bringing the perturbed state into the desired basin of attraction. The method has been applied to control both smooth and non-smooth systems, with the Duffing and impact oscillators used as examples. The strength of the intermittent control force is also considered, and a constrained intermittent control law is introduced to investigate the effect of limited control force on the efficiency of the controller. It is shown that increasing the duration of the control action and/or the number of control actuations allows one to successfully switch between the stable attractors using a lower control force. Numerical and experimental results are presented to demonstrate the effectiveness of the proposed method.

  12. Androgen Induces Adaptation to Oxidative Stress in Prostate Cancer: Implications for Treatment with Radiation Therapy

    Directory of Open Access Journals (Sweden)

    Jehonathan H. Pinthus

    2007-01-01

    Full Text Available Radiation therapy is a standard treatment for prostate cancer (PC. The postulated mechanism of action for radiation therapy is the generation of reactive oxygen species (ROS. Adjuvant androgen deprivation (AD therapy has been shown to confer a survival advantage over radiation alone in high-risk localized PC. However, the mechanism of this interaction is unclear. We hypothesize that androgens modify the radioresponsiveness of PC through the regulation of cellular oxidative homeostasis. Using androgen receptor (AR+ 22rv1 and AR− PC3 human PC cell lines, we demonstrated that testosterone increased basal reactive oxygen species (bROS levels, resulting in dose-dependent activation of phospho-p38 and pAKT, increased expression of clusterin, catalase, manganese superoxide dismutase. Similar data were obtained in three human PC xenografts; WISH-PC14, WISH-PC23, CWR22, growing in testosterone-supplemented or castrated SCID mice. These effects were reversible through AD or through incubation with a reducing agent. Moreover, testosterone increased the activity of catalase, superoxide dismutases, glutathione reductase. Consequently, AD significantly facilitated the response of AR+ cells to oxidative stress challenge. Thus, testosterone induces a preset cellular adaptation to radiation through the generation of elevated bROS, which is modified by AD. These findings provide a rational for combined hormonal and radiation therapy for localized PC.

  13. Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs).

    Science.gov (United States)

    Gao, Wenqing; Dalton, James T

    2007-03-01

    Selective androgen receptor modulators (SARMs) are a novel class of androgen receptor (AR) ligands that might change the future of androgen therapy dramatically. With improved pharmacokinetic characteristics and tissue-selective pharmacological activities, SARMs are expected to greatly extend the clinical applications of androgens to osteoporosis, muscle wasting, male contraception and diseases of the prostate. Mechanistic studies with currently available SARMs will help to define the contributions of differential tissue distribution, tissue-specific expression of 5alpha-reductase, ligand-specific regulation of gene expression and AR interactions with tissue-specific coactivators to their observed tissue selectivity, and lead to even greater expansion of selective anabolic therapies.

  14. Combined effects of food deprivation and food frequency on the amount and temporal distribution of schedule-induced drinking.

    Science.gov (United States)

    Castilla, José Luis; Pellón, Ricardo

    2013-11-01

    Under intermittent food schedules animals develop temporally organized behaviors throughout interfood intervals, with behaviors early in the intervals (interim) normally occurring in excess. Schedule-induced drinking (a prototype of interim, adjunctive behavior) is related to food deprivation and food frequency. This study investigated the interactions that resulted from combining different food-deprivation levels (70%, 80% or 90% free-feeding weights) with different food-occurrence frequencies (15-, 30- or 60-s interfood intervals) in a within-subjects design. Increases in food deprivation and food frequency generally led to increased licking, with greater differences due to food deprivation as interfood intervals became shorter. Distributions of licking were modestly shifted to later in the interfood interval as interfood intervals lengthened, a result that was most marked under 90% food deprivation, which also resulted in flatter distributions. It would therefore appear that food deprivation modulates the licking rate and the distribution of licking in different ways. Effects of food deprivation and food frequency are adequately explained by a theory of adjunctive behavior based on delayed food reinforcement, in contrast to alternative hypotheses. © Society for the Experimental Analysis of Behavior.

  15. ANABOLIC ANDROGENIC STEROIDS AND DEPENDENCE

    Directory of Open Access Journals (Sweden)

    IHSAN SARI

    2010-12-01

    Full Text Available Anabolic androgenic steroids are used for sportive, cosmetic, therapeutic and occupational reasons and there are many side effects reported (George, 2005; Nieminen et al., 1996; O'Sullivan et al., 2000. Prevalence of anabolic steroids’ use also indicates the importance of this topic. Moreover, it is now known that use of anabolic steroids could lead to dependence which could be psychological or/and physiological (Copeland et al., 2000. It isimportant to know about all aspects of anabolic steroids including dependence. Therefore, this study has attempted to give an insight into use of anabolic steroids and dependence. The discussion will focus on prevalence, reasons, and side effects of use and physiological and psychological dependence

  16. ABUSE OF ANABOLIC ANDROGENIC STEROIDS

    Directory of Open Access Journals (Sweden)

    Abbas Yavari

    2009-09-01

    Full Text Available According to the International Olympic Committee, the abuse of anabolic androgenic steroids (AASS is found in over 50% of positive doping tests. AASS abuse is not restricted to the organized sports andwidespread use. It remains as an unsolved public-health problem.Lower black market price, easier access to AASS, bodybuilding clubs and internet advertising are factors of this increasingly misuse. There is not real data about the prevalence of AASS abuse in various populations or countries, because most of athletes or students, due to their prohibition or ethical aspects do not admit to AASS abuse. Often they are aware of the risks of their choice and yet, are eager to put themselves at risk without deeper consideration. The abusers use them to improve their physical fitness and appearance.Present article has been collected to elucidate the risks and adverse effects of AASS and explanation of mechanisms of these events.

  17. Sleep Deprivation and Neurobehavioral Dynamics

    Science.gov (United States)

    Basner, Mathias; Rao, Hengyi; Goel, Namni; Dinges, David F.

    2013-01-01

    Lifestyles involving sleep deprivation are common, despite mounting evidence that both acute total sleep deprivation and chronically restricted sleep degrade neurobehavioral functions associated with arousal, attention, memory and state stability. Current research suggests dynamic differences in the way the central nervous system responds to acute versus chronic sleep restriction, which is reflected in new models of sleep-wake regulation. Chronic sleep restriction likely induces long-term neuromodulatory changes in brain physiology that could explain why recovery from it may require more time than from acute sleep loss. High intraclass correlations in neurobehavioral responses to sleep loss suggest that these trait-like differences are phenotypic and may include genetic components. Sleep deprivation induces changes in brain metabolism and neural activation that involve distributed networks and connectivity. PMID:23523374

  18. Adrenal Androgens and the Menopausal Transition

    OpenAIRE

    Lasley, B. L.; Crawford, S.; McConnell, D.S.

    2011-01-01

    The concept that adrenal androgen production gradually declines with age has changed following the analysis of the longitudinal data collected in the Study of Women’s Health Across the Nation (SWAN). It is now recognized that four adrenal androgens (3-beta hydroxy-5-androsten-17-one or dehydroepiandrosterone--DHEA, its sulfate, dehydroepiandrosterone sulfate--DHEAS; androst-4-ene, 3,17-dione or androstenedione; and androst-5-ene-3-beta, 17-beta diol, also known as androstenediol or Adiol) ris...

  19. Effects of sleep deprivation on prospective memory.

    Science.gov (United States)

    Grundgeiger, Tobias; Bayen, Ute J; Horn, Sebastian S

    2014-01-01

    Sleep deprivation reduces cognitive performance; however, its effects on prospective memory (remembering to perform intended actions) are unknown. One view suggests that effects of sleep deprivation are limited to tasks associated with prefrontal functioning. An alternative view suggests a global, unspecific effect on human cognition, which should affect a variety of cognitive tasks. We investigated the impact of sleep deprivation (25 hours of sleep deprivation vs. no sleep deprivation) on prospective-memory performance in more resource-demanding and less resource-demanding prospective-memory tasks. Performance was lower after sleep deprivation and with a more resource-demanding prospective-memory task, but these factors did not interact. These results support the view that sleep deprivation affects cognition more globally and demonstrate that sleep deprivation increases failures to carry out intended actions, which may have severe consequences in safety-critical situations.

  20. SOCIODEMOGRAPHIC DOAMINS OF DEPRIVATION AND PRETERM BIRTH

    Science.gov (United States)

    Background. Neighborhood-level deprivation has long been associated with adverse outcomes, including preterm birth (PTB), as observed in the authors' previous work using a composite deprivation index. Area disadvantage is multifaceted comprising income, employment, education and...

  1. The effect of testosterone on androgen receptors and human penile growth.

    Science.gov (United States)

    Baskin, L S; Sutherland, R S; DiSandro, M J; Hayward, S W; Lipschutz, J; Cunha, G R

    1997-09-01

    Recent rat studies suggest that early exposure to exogenous testosterone accelerates the loss of androgen receptors and compromises eventual penile length. In humans we hypothesize that down regulation of the androgen receptor is not the mechanism that stops penile growth. To test this hypothesis we investigated the effects of androgen deprivation and supplementation on the developing human penis. A total of 15 normal human fetal penises at 7 to 19 weeks of gestation (mean plus or minus standard deviation 12 +/- 4.5) was divided in half sagittally. Specimens were grafted beneath the renal capsule of male athymic nude mice or nude rats. Three groups of host animals were prepared, including 10 with no testosterone that were castrated at grafting, 15 with testosterone and 5 with super testosterone in which 50 mg. testosterone propionate pellets were implanted subcutaneously at grafting. Each fetal penile specimen was its own control, since half was implanted into an intact animal and the other into a castrated or super testosterone host. Six weeks after grafting the specimens were analyzed for gross size (length), histology and expression of androgen receptors. All human fetal penile specimens grew from the nadir size and appeared as white exophytic growths on the surface of the host kidneys. Normal grafts were larger than castrate specimens (mean 6.9 +/- 2.1 versus 3.9 +/- 2.1 mm., p = 0.014). Mean length of the super testosterone specimens (7.3 +/- 2.3 mm.) was not significantly greater than that of normal specimens (p = 0.797). Histological analysis revealed that all specimens were composed of viable penile tissue. Cellular density of the castrate penises was approximately 2 times greater than that of the normal and super testosterone specimens (40.6 +/- 5.9 versus 25.1 +/- 2.8 cells per cm.2, p > 0.001), as calculated on enlarged micrographs. Supraphysiological doses of testosterone did not change the histology compared to controls. Immunohistochemical

  2. Phenotypic Plasticity, Bet-Hedging, and Androgen Independence in Prostate Cancer: Role of Non-Genetic Heterogeneity

    Directory of Open Access Journals (Sweden)

    Mohit Kumar Jolly

    2018-03-01

    Full Text Available It is well known that genetic mutations can drive drug resistance and lead to tumor relapse. Here, we focus on alternate mechanisms—those without mutations, such as phenotypic plasticity and stochastic cell-to-cell variability that can also evade drug attacks by giving rise to drug-tolerant persisters. The phenomenon of persistence has been well-studied in bacteria and has also recently garnered attention in cancer. We draw a parallel between bacterial persistence and resistance against androgen deprivation therapy in prostate cancer (PCa, the primary standard care for metastatic disease. We illustrate how phenotypic plasticity and consequent mutation-independent or non-genetic heterogeneity possibly driven by protein conformational dynamics can stochastically give rise to androgen independence in PCa, and suggest that dynamic phenotypic plasticity should be considered in devising therapeutic dosing strategies designed to treat and manage PCa.

  3. Bearding the Capability Deprivation Machine: The Pedagogical ...

    African Journals Online (AJOL)

    Drawing on Sen and his ideas of capability deprivation, it is contended here that income-deprivation ideas by themselves do not adequately encompass the full complexity of how deprivation works. The approach taken here, therefore, is different. It works with the proposition that education needs to respond to the full range ...

  4. Androgen Bioassay for the Detection of Nonlabeled Androgenic Compounds in Nutritional Supplements.

    Science.gov (United States)

    Cooper, Elliot R; McGrath, Kristine C Y; Li, XiaoHong; Heather, Alison K

    2018-01-01

    Both athletes and the general population use nutritional supplements. Athletes often turn to supplements hoping that consuming the supplement will help them be more competitive and healthy, while the general population hopes to improve body image or vitality. While many supplements contain ingredients that may have useful properties, there are supplements that are contaminated with compounds that are banned for use in sport or have been deliberately adulterated to fortify a supplement with an ingredient that will produce the advertised effect. In the present study, we have used yeast cell and mammalian cell androgen bioassays to characterize the androgenic bioactivity of 112 sports supplements available from the Australian market, either over the counter or via the Internet. All 112 products did not declare an androgen on the label as an included ingredient. Our findings show that six out of 112 supplements had strong androgenic bioactivity in the yeast cell bioassay, indicating products spiked or contaminated with androgens. The mammalian cell bioassay confirmed the strong androgenic bioactivity of five out of six positive supplements. Supplement 6 was metabolized to weaker androgenic bioactivity in the mammalian cells. Further to this, Supplement 6 was positive in a yeast cell progestin bioassay. Together, these findings highlight that nutritional supplements, taken without medical supervision, could expose or predispose users to the adverse consequences of androgen abuse. The findings reinforce the need to increase awareness of the dangers of nutritional supplements and highlight the challenges that clinicians face in the fast-growing market of nutritional supplements.

  5. Multidimensional child deprivation in Iran

    NARCIS (Netherlands)

    Yousefzadeh Faal Daghati, Sepideh; Mideros-Mora, Andrés; De Neubourg, Chris; Minujin, Alberto; Nandy, Shailen

    The chapter analyses children's multidimensional deprivation in Iran in 2009 and explores inequalities in different regions. The study focused on outcome indicators, with the level of analysis focusing on the individual child as well as the household. A child rights approach is applied to define

  6. Relative Deprivation with Imperfect Information

    OpenAIRE

    Paolo Verme; Rima Izem

    2008-01-01

    The paper proposes an alternative index of relative deprivation which allows for selection of the reference group and imperfect information, two central elements of modern theories of social justice. An application to real data and a simulation on artificial data illustrate the use and some properties of the index.

  7. Do androgens control the uptake of {sup 18}F-FDG, {sup 11}C-choline and {sup 11}C-acetate in human prostate cancer cell lines?

    Energy Technology Data Exchange (ETDEWEB)

    Emonds, Kimy M.; Nuyts, Johan; Mortelmans, Luc [University Hospital Gasthuisberg Leuven, Department of Nuclear Medicine, Leuven (Belgium); Swinnen, Johannes V.; Vanderhoydonc, Frank [K.U. Leuven, Laboratory for Experimental Medicine and Endocrinology, Department of Experimental Medicine, Leuven (Belgium); Weerden, Wytske M. van [Erasmus University Rotterdam, Department of Experimental Urology, Josephine Nefkens Institute, Rotterdam (Netherlands); Mottaghy, Felix M. [University Hospital Gasthuisberg Leuven, Department of Nuclear Medicine, Leuven (Belgium); University Hospital Aachen, Department of Nuclear Medicine, Aachen (Germany); Maastricht University Medical Center, Department of Nuclear Medicine, Maastricht (Netherlands)

    2011-10-15

    The aim of this study was to evaluate the impact of androgen ablation therapy in different prostate cancer (PCa) cell lines - reflecting different stages of the disease - on {sup 18}F-fluorodeoxyglucose (FDG), {sup 11}C-choline and {sup 11}C-acetate uptake. Uptake experiments were performed in androgen-sensitive (LNCaP, PC346C) and independent cell lines (22Rv1, PC346DCC, PC-3) as well as in a benign prostatic hyperplasia (BPH-1) cell line. Tracer uptake was assessed under androgen ablation. Results of the cancer cell lines were normalized to those of BPH-1. To evaluate the effect of androgen on the uptake of {sup 18}F-FDG, {sup 11}C-choline and {sup 11}C-acetate in PCa cell lines, 10{sup -8}M R1881, 10{sup -10}M R1881, the combination of 10{sup -10}M R1881 plus 10{sup -6}M Casodex or 10{sup -6}M Casodex alone were added in parallel cell cultures 1 day before uptake experiments. Uptake in androgen-supplemented cell cultures was compared to the uptake under androgen deprivation. Uptake was corrected for cell number using protein content. Compared to BPH-1, a higher {sup 18}F-FDG uptake was observed only in PC346C cells, whereas a higher {sup 11}C-choline and markedly increased {sup 11}C-acetate uptake was seen in all cancer cell lines. Androgens significantly modulated the uptake of {sup 18}F-FDG in LNCaP, PC346C and 22Rv1 cells, and of {sup 11}C-choline in the PC346C and 22Rv1 cell line. No androgenic effect on {sup 11}C-choline and {sup 18}F-FDG uptake was observed in PC-3 and PC346DCC cells. {sup 11}C-Acetate uptake was independent of androgen status in all PCa cell lines studied. {sup 18}F-FDG uptake in PCa cell lines showed the highest variability and strongest androgen effect, suggesting its poor potential for metabolic imaging of advanced PCa. In contrast to {sup 18}F-FDG and {sup 11}C-choline, {sup 11}C-acetate uptake was unaffected by androgens and thus {sup 11}C-acetate seems best for monitoring PCa progression. (orig.)

  8. Obesity and androgens: facts and perspectives.

    Science.gov (United States)

    Pasquali, Renato

    2006-05-01

    This review discusses androgen status in male and female obesity, according to their specific phenotype, and the main mechanisms responsible. Published data in the literature of the last 20 years represented the basis of most of the data and concepts incorporated in the review. Obesity is associated with profound alterations in androgen secretion, transport, metabolism, and action, according to a dichotomous behavior depending on sex. Obese men are characterized by a progressive decrease of testosterone levels with increasing body weight, whereas obese women, particularly those with the abdominal phenotype, tend to develop a condition of functional hyperandrogenism. Reduced sex hormone-binding globulin synthesis and circulating blood levels represent the sole common mechanism which is responsible in both sexes. Among other still partially undefined factors, mechanisms potentially responsible for the sex dichotomy in androgen levels involve specific alterations of gonadotropin secretion, estrogens, the hypothalamic-pituitary-adrenal axis, leptin, androgen receptors, specific steroidogenic enzymes in the peripheral tissues, and, possibly, ghrelin. In both sexes, androgens play an important role in determining the sex-dependent pattern of body fat distribution. Moreover there are theoretical possibilities that low testosterone in men and high free testosterone fraction in women may play a role in the development of the metabolic syndrome. This is exemplified by the well defined association between obesity and other features of the metabolic syndrome in women with polycystic ovary syndrome and in hypogonadal men. The effects of androgen and antiandrogens in obese men and women also represent arguments in favor of this association. Given the fundamental role of sex hormones in the regulation of body composition, fuel homeostasis, and reproduction in humans, more emphasis should be placed on the potential role of androgen dysregulation in the pathophysiology of different

  9. Effects of Hormone Deprivation, 2-Methoxyestradiol Combination Therapy on Hormone-Dependent Prostate Cancer In Vivo

    Directory of Open Access Journals (Sweden)

    Fuminori Sato

    2005-09-01

    Full Text Available 2-Methoxyestradiol (2-ME has potent anti proliferative effects on cancer cells. Its utility alone or in combination with other therapies for treating prostate cancer, however, has not been fully explored. Androgendependent, independent human prostate cancer cells were examined in vivo for their response to combination therapy. Efficacy was assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay, measuring microvessel density (MVD in excised tumors. Animals harboring hormonedependent tumors treated with 2-ME alone, androgen deprivation therapy alone, or the combination of the two had a 3.1-fold, 5.3-fold, 10.1-fold increase in apoptosis, respectively. For hormone-independent tumors, treatment with 2-ME resulted in a 2.43-fold increase in apoptosis, a 73% decrease in MVD. 2-ME was most effective against hormone-dependent tumors in vivo, combination therapy resulted in a significant increase in efficacy compared to no treatment controls, trended toward greater efficacy than either 2-ME or androgen deprivation alone. Combination therapy should be investigated further as an additional therapeutic option for early prostate cancer.

  10. Anabolic-androgenic steroids for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, Andrea; Iaquinto, Gaetano; Gluud, Christian

    2002-01-01

    The objectives were to assess the beneficial and harmful effects of anabolic-androgenic steroids for alcoholic liver disease.......The objectives were to assess the beneficial and harmful effects of anabolic-androgenic steroids for alcoholic liver disease....

  11. Three novel and two known androgen receptor gene mutations ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 95; Issue 4. Three novel and two known androgen receptor gene mutations associated with androgen insensitivity syndrome in sex-reversed XY female patients. BALACHANDRAN SARANYA GUNASEKARAN BHAVANI BRINDHA ARUMUGAM MEENA JAYASHANKAR ...

  12. Football training improves lean body mass in men with prostate cancer undergoing androgen deprivation therapy

    DEFF Research Database (Denmark)

    Uth, J; Hornstrup, Therese; Schmidt, Jakob Friis

    2014-01-01

    ). Fifty-seven men aged 67 (range: 43-74) were randomly assigned to a football group (FG, n = 29) or a usual care control group (CON, n = 28). The primary outcome was change in lean body mass (LBM) assessed by dual-energy X-ray absorptiometry scanning. Secondary outcomes included changes in knee......-extensor muscle strength (one repetition maximum), fat percentage, and maximal oxygen uptake (VO2max ). Mean heart rate during training was 137.7 (standard deviation 13.7) bpm or 84.6 (3.9)% HRmax. In FG, LBM increased by 0.5 kg [95% confidence interval (CI) 0.1-0.9; P = 0.02] with no change in CON (mean group...... difference 0.7 kg; 95% CI 0.1-1.2; P = 0.02). Also, muscle strength increased in FG (8.9 kg; 95% CI 6.0-11.8; P fat percentage tended to decrease (0...

  13. Cardiovascular mortality in patients with prostate cancer exposed to androgen deprivation therapy.

    Science.gov (United States)

    Monzó-Gardiner, J I; Herranz-Amo, F

    2015-10-01

    A relationship between the administration of GnRH agonists and the risk of acute myocardial infarction (AMC) in patients with prostate cancer has been showed in the third observational study published in April 2014. The association AMC-orchiectomy was not found in any of these studies. Define risk factors for cardiovascular disease in patients treated with GnRH agonist. Their probable underlying pathogenic mechanism in the myocardium and peripheral vascular tree was also analyzed. English articles cited in PubMed were reviewed. No time period is specified. The last search date was 11/30/14. In patients with coronary history of AMC or congestive heart failure, hormonal neoadjuvant therapy increased cardiovascular mortality rates (HR: 1.96, IC 95%: 1.04-3.71; P=.04) as well as cardiovascular-specific mortality rates (AHR: 3.28; IC 95%: 1.01-10.64; P=.048). Two possible mechanisms can be involved: a) direct mechanism through myocardial receptor for GnRH/PKA along with atherogenic plaques; and b) indirect mechanism related with metabolic disturbances. Patients with AMC or congestive heart failure history could present a higher risk of death related to the use of GnRH agonists. In these cases, should carefully consider appropriateness of such treatment. These effects can explained by a direct mechanism on myocardium and peripheral vascular tree and indirect ones related with modified metabolic syndrome. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Down-regulation of DcR2 sensitizes androgen-dependent prostate cancer LNCaP cells to TRAIL-induced apoptosis

    Directory of Open Access Journals (Sweden)

    Vindrieux David

    2011-12-01

    Full Text Available Abstract Background Dysregulation of many apoptotic related genes and androgens are critical in the development, progression, and treatment of prostate cancer. The differential sensitivity of tumour cells to TRAIL-induced apoptosis can be mediated by the modulation of surface TRAIL receptor expression related to androgen concentration. Our previous results led to the hypothesis that downregulation of TRAIL-decoy receptor DcR2 expression following androgen deprivation would leave hormone sensitive normal prostate cells vulnerable to the cell death signal generated by TRAIL via its pro-apoptotic receptors. We tested this hypothesis under pathological conditions by exploring the regulation of TRAIL-induced apoptosis related to their death and decoy receptor expression, as also to hormonal concentrations in androgen-sensitive human prostate cancer, LNCaP, cells. Results In contrast to androgen-insensitive PC3 cells, decoy (DcR2 and death (DR5 receptor protein expression was correlated with hormone concentrations and TRAIL-induced apoptosis in LNCaP cells. Silencing of androgen-sensitive DcR2 protein expression by siRNA led to a significant increase in TRAIL-mediated apoptosis related to androgen concentration in LNCaP cells. Conclusions The data support the hypothesis that hormone modulation of DcR2 expression regulates TRAIL-induced apoptosis in LNCaP cells, giving insight into cell death induction in apoptosis-resistant hormone-sensitive tumour cells from prostate cancer. TRAIL action and DcR2 expression modulation are potentially of clinical value in advanced tumour treatment.

  15. Salbutamol exhibits androgenic activity in vitro

    Science.gov (United States)

    von Bueren, André O; Ma, Risheng; Schlumpf, Margret; Lichtensteiger, Walter

    2007-01-01

    Background Salbutamol has been shown to mediate anabolic effects after intravenous administration. However, the mechanism responsible for the anabolic actions of salbutamol remains unknown. Aim To investigate the potential mechanism by which salbutamol mediates anabolic effects in vitro. Methods The potential androgenic activity of salbutamol was investigated in vitro by the A‐Screen assay that measures androgen‐dependent inhibition of proliferation of the androgen receptor (AR)‐positive human mammary carcinoma cell line, MCF7‐AR1. Results The assay was validated with three known androgens; methyltrienolone (R1881), 5α‐dihydrotestosterone (DHT) and danazol. IC50 values of R1881, DHT and danazol, 4.41×10–11, 4.44×10−11 and 1.08×10−8 M, respectively, were in the ranges known from earlier studies. Our results demonstrate that salbutamol exhibits androgenic activity, with an IC50 value of 8.93×10−6 M. Anti‐estrogenic or cytotoxic effects, which might have interfered with the assay, were excluded by additional experiments on wild‐type MCF7 and MCF7‐AR1 cells, respectively. Conclusion These data indicate that salbutamol exerts anabolic effects through androgen receptor agonistic activity in vitro. PMID:17510230

  16. Discovery AND Therapeutic Promise OF Selective Androgen Receptor Modulators

    Science.gov (United States)

    Chen, Jiyun; Kim, Juhyun; Dalton, James T.

    2007-01-01

    Androgens are essential for male development and the maintenance of male secondary characteristics, such as bone mass, muscle mass, body composition, and spermatogenesis. The main disadvantages of steroidal androgens are their undesirable physicochemical and pharmacokinetic properties. The recent discovery of nonsteroidal selective androgen receptor modulators (SARMs) provides a promising alternative for testosterone replacement therapies with advantages including oral bioavailability, flexibility of structural modification, androgen receptor specificity, tissue selectivity, and the lack of steroid-related side effects. PMID:15994457

  17. Empirical heuristics for improving Intermittent Demand Forecasting

    OpenAIRE

    Petropoulos, Fotios; Nikolopoulos, Konstantinos; Spithourakis, George; Assimakopoulos, Vassilios

    2013-01-01

    Purpose– Intermittent demand appears sporadically, with some time periods not even displaying any demand at all. Even so, such patterns constitute considerable proportions of the total stock in many industrial settings. Forecasting intermittent demand is a rather difficult task but of critical importance for corresponding cost savings. The current study aims to examine the empirical outcomes of three heuristics towards the modification of established intermittent demand forecasting approaches...

  18. Enhanced Androgen Signaling With Androgen Receptor Overexpression in the Osteoblast Lineage Controls Skeletal Turnover, Matrix Quality and Bone Architecture

    National Research Council Canada - National Science Library

    Wiren, Kristine M; Jepsen, Karl

    2006-01-01

    .... We genetically engineered transgenic mice in which androgen receptor (AR) overexpression is skeletally targeted in two separate models to better understand the role of androgen signaling directly in bone...

  19. SLEEP DEPRIVATION AND CARDIOVASCULAR RISK

    Directory of Open Access Journals (Sweden)

    V. А. Vizir

    2013-06-01

    Full Text Available In a review article extensively discusses the relationship between sleep duration and cardiovascular diseases. Sleep loss is a common condition in developed countries, with evidence showing that people in Western countries are sleeping on average only 6.8 hour per night, 1.5 hour less than a century ago. Although the effect of sleep deprivation on the human body is not completely unexplained, recent epidemiological studies have revealed relationships between sleep deprivation and arterial hypertension, coronary heart disease and diabetes mellitus. Increased sympathetic nervous system activity and changes in melatonin secretion are considered as the main pathophysiological mechanisms involved in the development and progression of cardiovascular disease in patients with insufficient duration of nighttime sleep. Adequate sleep duration may be important for preventing cardiovascular diseases in modern society.

  20. Three novel and two known androgen receptor gene mutations ...

    Indian Academy of Sciences (India)

    gene mutations associated with androgen insensitivity syndrome in sex-reversed XY female patients. J. Genet. ... signal and a C-terminal. Keywords. androgen insensitivity syndrome; androgen receptor; truncation mutation; N-terminal domain; XY sex reversal. .... and an increased risk of gonadal tumour. Mutations in SRY.

  1. Sleep Deprivation and the Epigenome

    OpenAIRE

    Marie E. Gaine; Snehajyoti Chatterjee; Ted Abel

    2018-01-01

    Sleep deprivation disrupts the lives of millions of people every day and has a profound impact on the molecular biology of the brain. These effects begin as changes within a neuron, at the DNA and RNA level, and result in alterations in neuronal plasticity and dysregulation of many cognitive functions including learning and memory. The epigenome plays a critical role in regulating gene expression in the context of memory storage. In this review article, we begin by describing the effects of e...

  2. Deprival value: information utility analysis

    Directory of Open Access Journals (Sweden)

    Marco Antonio Pereira

    Full Text Available ABSTRACT This article contributes to the perception that the users’ learning process plays a key role in order to apply an accounting concept and this involves a presentation that fits its informative potential, free of previous accounting fixations. Deprival value is a useful measure for managerial and corporate purposes, it may be applied to the current Conceptual Framework of the International Accounting Standards Board (IASB. This study analyzes its utility, taking into account cognitive aspects. Also known as value to the business, deprival value is a measurement system that followed a path where it was misunderstood, confused with another one, it faced resistance to be implemented and fell into disuse; everything that a standardized measurement method tries to avoid. In contrast, deprival value has found support in the academy and in specific applications, such as those related to the public service regulation. The accounting area has been impacted by sophistication of the measurement methods that increasingly require the ability to analyze accounting facts on an economic basis, at the risk of loss of their information content. This development becomes possible only when the potential of a measurement system is known and it is feasible to be achieved. This study consists in a theoretical essay based on literature review to discuss its origin, presentation, and application. Considering the concept’s cognitive difficulties, deprival value was analyzed, as well as its corresponding heteronym, value to the business, in order to explain some of these changes. The concept’s utility was also explored through cross-analysis with impairment and the scheme developed was applied to actual economic situations faced by a company listed on stock exchange.

  3. Partial Androgen Insensitivity Syndrome Presenting with Gynecomastia

    Directory of Open Access Journals (Sweden)

    Sung Won Lee

    2015-06-01

    Full Text Available Gynecomastia is a benign enlargement of the male breast caused by the proliferation of glandular breast tissue. Determining the various causes of gynecomastia such as physiological causes, drugs, systemic diseases, and endocrine disorders is important. Androgen insensitivity syndrome (AIS is a rare endocrine disorder presenting with gynecomastia and is a disorder of male sexual differentiation caused by mutations within the androgen receptor gene. All individuals with AIS have the 46 XY karyotype, although AIS phenotypes can be classified as mild, partial or complete and can differ among both males and females including ambiguous genitalia or infertility in males. We experienced a case of partial AIS presenting with gynecomastia and identified the androgen receptor gene mutation.

  4. Age, performance and sleep deprivation.

    Science.gov (United States)

    Philip, Pierre; Taillard, Jacques; Sagaspe, Patricia; Valtat, Cédric; Sanchez-Ortuno, Montserrat; Moore, Nicholas; Charles, André; Bioulac, Bernard

    2004-06-01

    Young subjects are frequently involved in sleep-related accidents. They could be more affected than older drivers by sleep loss and therefore worsen their driving skills quicker, or have a different perception of their level of impairment. To test these hypotheses we studied variations of reaction time (RT), a fundamental prerequisite for safe performing, as measured by lapses, i.e. responses > or = 500 ms and self-assessment of performance and sleepiness after a night awake and after a night asleep in a balanced crossover design in young versus older healthy subjects. Ten young (20-25 years old) and 10 older volunteers (52-63 years old) were tested with and without 24 h of sleep deprivation. Without sleep deprivation, RTs were slower in older subjects than in the younger ones. However, after sleep deprivation, the RTs of young subjects increased while that of the older subjects remained almost unaffected. Sleepiness and self-perception of performance were equally affected in both age groups showing different perception of performance in the age groups. Our findings are discussed in terms of vulnerability to sleep-related accidents.

  5. Bioactive Androgens and Glucuronidated Androgen Metabolites are Associated with Subcutaneous and Ectopic Skeletal Muscle Adiposity among Older Black Men

    OpenAIRE

    Miljkovic, Iva; Cauley, Jane A; Dressen, Amy S; Gordon, Christopher L; Goodpaster, Bret H; Kuller, Lewis H; Bunker, Clareann H; Patrick, Alan L; Wheeler, Victor W; Orwoll, Eric S; Zmuda, Joseph M

    2011-01-01

    Aging is associated with declining serum levels of androgenic hormones and with increased skeletal muscle fat infiltration, an emerging risk factor for type 2 diabetes mellitus (T2DM). Androgens regulate fat mass and glucose homeostasis, but the effect of androgenic hormones on skeletal muscle fat infiltration is largely unknown. Thus, the aim of the current study was to examine the association of serum androgens and their precursors and metabolites with skeletal muscle fat infiltration and T...

  6. Pharmacodynamics of selective androgen receptor modulators.

    Science.gov (United States)

    Yin, Donghua; Gao, Wenqing; Kearbey, Jeffrey D; Xu, Huiping; Chung, Kiwon; He, Yali; Marhefka, Craig A; Veverka, Karen A; Miller, Duane D; Dalton, James T

    2003-03-01

    The present study aimed to identify selective androgen receptor modulators (SARMs) with in vivo pharmacological activity. We examined the in vitro and in vivo pharmacological activity of four chiral, nonsteroidal SARMs synthesized in our laboratories. In the in vitro assays, these compounds demonstrated moderate to high androgen receptor (AR) binding affinity, with K(i) values ranging from 4 to 37 nM, and three of the compounds efficaciously stimulated AR-mediated reporter gene expression. The compounds were then administered subcutaneously to castrated rats to appraise their in vivo pharmacological activity. Androgenic activity was evaluated by the ability of these compounds to maintain the weights of prostate and seminal vesicle, whereas levator ani muscle weight was used as a measure of anabolic activity. The maximal response (E(max)) and dose for half-maximal effect (ED(50)) were determined for each compound and compared with that observed for testosterone propionate (TP). Compounds S-1 and S-4 demonstrated in vivo androgenic and anabolic activity, whereas compounds S-2 and S-3 did not. The activities of S-1 and S-4 were tissue-selective in that both compounds stimulated the anabolic organs more than the androgenic organs. These two compounds were less potent and efficacious than TP in androgenic activity, but their anabolic activity was similar to or greater than that of TP. Neither S-1 nor S-4 caused significant luteinizing hormone or follicle stimulating hormone suppression at doses near the ED(50) value. Thus, compounds S-1 and S-4 were identified as SARMs with potent and tissue-selective in vivo pharmacological activity, and represent the first members of a new class of SARMs with selective anabolic effects.

  7. Adrenal androgens and the menopausal transition.

    Science.gov (United States)

    Lasley, Bill L; Crawford, Sybil; McConnell, Daniel S

    2011-09-01

    The concept that adrenal androgen production gradually declines with age has changed after analysis of longitudinal data from the Study of Women's Health Across the Nation (SWAN). It is now recognized that 4 adrenal androgens rise during the menopausal transition in most women. Ethnic and individual differences in sex steroids are more apparent in circulating adrenal steroids than in either estradiol or cyclic ovarian steroid hormone profiles, particularly during the early and late perimenopause. Thus, adrenal steroid production may play a larger role in the occurrence of symptoms and the potential for healthier aging than previously recognized.

  8. Regulation of expression of Na+,K+-ATPase in androgen-dependent and androgen-independent prostate cancer

    NARCIS (Netherlands)

    L.J. Blok (Leen); G.T.G. Chang; M. Steenbeek-Slotboom (M.); W.M. van Weerden (Wytske); H.G. Swarts; J.J.H.H.M. de Pont (J. J H H M); G.J. van Steenbrugge (Gert Jan); A.O. Brinkmann (Albert)

    1999-01-01

    textabstractThe β1-subunit of Na+,K+-ATPase was isolated and identified as an androgen down-regulated gene. Expression was observed at high levels in androgen-independent as compared to androgen-dependent (responsive) human prostate cancer cell lines and xenografts when grown in the presence of

  9. Antioxidants Abrogate Alpha-Tocopherylquinone-Mediated Down-Regulation of the Androgen Receptor in Androgen-Responsive Prostate Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Alexandra M Fajardo

    Full Text Available Tocopherylquinone (TQ, the oxidation product of alpha-tocopherol (AT, is a bioactive molecule with distinct properties from AT. In this study, AT and TQ are investigated for their comparative effects on growth and androgenic activity in prostate cancer cells. TQ potently inhibited the growth of androgen-responsive prostate cancer cell lines (e.g., LAPC4 and LNCaP cells, whereas the growth of androgen-independent prostate cancer cells (e.g., DU145 cells was not affected by TQ. Due to the growth inhibitory effects induced by TQ on androgen-responsive cells, the anti-androgenic properties of TQ were examined. TQ inhibited the androgen-induced activation of an androgen-responsive reporter and inhibited the release of prostate specific antigen from LNCaP cells. TQ pretreatment was also found to inhibit AR activation as measured using the Multifunctional Androgen Receptor Screening assay. Furthermore, TQ decreased androgen-responsive gene expression, including TM4SF1, KLK2, and PSA over 5-fold, whereas AT did not affect the expression of androgen-responsive genes. Of importance, the antiandrogenic effects of TQ on prostate cancer cells were found to result from androgen receptor protein down-regulation produced by TQ that was not observed with AT treatment. Moreover, none of the androgenic endpoints assessed were affected by AT. The down-regulation of androgen receptor protein by TQ was abrogated by co-treatment with antioxidants. Overall, the biological actions of TQ were found to be distinct from AT, where TQ was found to be a potent inhibitor of cell growth and androgenic activity in androgen-responsive prostate cancer cells.

  10. PTTG1, A novel androgen responsive gene is required for androgen-induced prostate cancer cell growth and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zheng [Department of Urology, First Hospital, Peking University & Institute of Urology, Peking University, Beijing 100034 (China); Jin, Bo [Department of Clinical Laboratory, Peking University First Hospital, Beijing 100034 (China); Jin, Yaqiong [Biobank for Clinical Data and Samples in Pediatric, Beijing Pediatric Research Institute, Beijing Children' s Hospital, Capital Medical University, Beijing 100045 (China); Huang, Shengquan; Niu, Xiaohua [Department of Urology, First Hospital, Peking University & Institute of Urology, Peking University, Beijing 100034 (China); Mao, Zebin [The Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, 38 Xueyuan Road, Beijing 100191 (China); Xin, Dianqi, E-mail: xin-dianqi@163.com [Department of Urology, First Hospital, Peking University & Institute of Urology, Peking University, Beijing 100034 (China)

    2017-01-01

    Androgens (AR) play an important role in initiation and progression of prostate cancer. It has been shown that AR exert their effects mainly through the androgen-activated AR which binds to androgen response elements (AREs) in the regulatory regions of target genes to regulate the transcription of androgen-responsive genes, thus, identification of AR downstream target gene is critical to understand androgen function in prostate cancer. In this study, our results showed that androgen treatment of LNCaP cells induced PTTG1 expression, which was blocked by the androgen receptor antagonist, Casodex. Bioinformatics analysis and experiments using PTTG1 promoter deletion mutants showed that the PTTG1 promoter contains a putative androgen response element (ARE), which localizes in the −851 to −836 region of the promoter. Androgen activated androgen receptor (AR) binding to this ARE was confirmed by Chromatin immunoprecipitation (ChIP) assay. Furthermore, Knockdown of PTTG1 expression using short hairpin RNA significantly reduced androgen-induced LNCaP cell growth and invasion. In addition, we showed PTTG1 is highly expressed in metastasis prostate cancer tissue. These results suggest that PTTG1 is a novel downstream target gene of androgen receptor and take part in prostate cancer proliferation and metastasis. - Highlights: • Androgen treatment of LNCaP cells induced PTTG1 expression. • Knockdown of PTTG1 expression significantly reduced androgen-induced LNCaP cell growth and invasion. • PTTG1 is highly expressed in metastasis prostate cancer tissue. • PTTG1 is a novel downstream target gene of androgen receptor.

  11. Recovery of neurofilament following early monocular deprivation

    Directory of Open Access Journals (Sweden)

    Timothy P O'Leary

    2012-04-01

    Full Text Available A brief period of monocular deprivation in early postnatal life can alter the structure of neurons within deprived-eye-receiving layers of the dorsal lateral geniculate nucleus. The modification of structure is accompanied by a marked reduction in labeling for neurofilament, a protein that composes the stable cytoskeleton and that supports neuron structure. This study examined the extent of neurofilament recovery in monocularly deprived cats that either had their deprived eye opened (binocular recovery, or had the deprivation reversed to the fellow eye (reverse occlusion. The degree to which recovery was dependent on visually-driven activity was examined by placing monocularly deprived animals in complete darkness (dark rearing. The loss of neurofilament and the reduction of soma size caused by monocular deprivation were both ameliorated equally following either binocular recovery or reverse occlusion for 8 days. Though monocularly deprived animals placed in complete darkness showed recovery of soma size, there was a generalized loss of neurofilament labeling that extended to originally non-deprived layers. Overall, these results indicate that recovery of soma size is achieved by removal of the competitive disadvantage of the deprived eye, and occurred even in the absence of visually-driven activity. Recovery of neurofilament occurred when the competitive disadvantage of the deprived eye was removed, but unlike the recovery of soma size, was dependent upon visually-driven activity. The role of neurofilament in providing stable neural structure raises the intriguing possibility that dark rearing, which reduced overall neurofilament levels, could be used to reset the deprived visual system so as to make it more ameliorable with treatment by experiential manipulations.

  12. Transfection of Sertoli cells with androgen receptor alters gene expression without androgen stimulation.

    Science.gov (United States)

    Fietz, D; Markmann, M; Lang, D; Konrad, L; Geyer, J; Kliesch, S; Chakraborty, T; Hossain, H; Bergmann, M

    2015-12-29

    Androgens play an important role for the development of male fertility and gained interest as growth and survival factors for certain types of cancer. Androgens act via the androgen receptor (AR/Ar), which is involved in various cell biological processes such as sex differentiation. To study the functional mechanisms of androgen action, cell culture systems and AR-transfected cell lines are needed. Transfection of AR into cell lines and subsequent gene expression analysis after androgen treatment is well established to investigate the molecular biology of target cells. However, it remains unclear how the transfection with AR itself can modulate the gene expression even without androgen stimulation. Therefore, we transfected Ar-deficient rat Sertoli cells 93RS2 by electroporation using a full length human AR. Transfection success was confirmed by Western Blotting, immunofluorescence and RT-PCR. AR transfection-related gene expression alterations were detected with microarray-based genome-wide expression profiling of transfected and non-transfected 93RS2 cells without androgen stimulation. Microarray analysis revealed 672 differentially regulated genes with 200 up- and 472 down-regulated genes. These genes could be assigned to four major biological categories (development, hormone response, immune response and metabolism). Microarray results were confirmed by quantitative RT-PCR analysis for 22 candidate genes. We conclude from our data, that the transfection of Ar-deficient Sertoli cells with AR has a measurable effect on gene expression even without androgen stimulation and cause Sertoli cell damage. Studies using AR-transfected cells, subsequently stimulated, should consider alterations in AR-dependent gene expression as off-target effects of the AR transfection itself.

  13. Probabilistic signatures of spatiotemporal intermittency in the ...

    Indian Academy of Sciences (India)

    where spatiotemporal intermittency with travelling wave laminar states and solitons is seen at points marked with boxes (2). (b) The space-time plot of spatiotemporal intermittency with solitons. the strength of nonlinearity in the map and Ω is the frequency of the map in the absence of nonlinearity. The phase diagram of the ...

  14. Intermittent behavior of the logistic system

    Science.gov (United States)

    Mayer-Kress, G.; Haken, H.

    1981-03-01

    In the discrete logistic model a transition to chaotic behavior via intermittency occurs in a neighborhood of periodic bands. Intermittent behavior is also induced if a stable periodic orbit is perturbed by low-level external noise, whereas alterations due to computer digitalisation produce remarkable periodicities. We compare our numerical results with the predictions of Pomeau and Manneville for the Lorenz system.

  15. Probabilistic signatures of spatiotemporal intermittency in the ...

    Indian Academy of Sciences (India)

    with triangles (△) and asterisks (∗). Inset shows a part of the phase diagram where spatiotemporal intermittency with travelling wave laminar states and solitons is seen at points marked with boxes (2). (b) The space-time plot of spatiotemporal intermittency with solitons. the strength of nonlinearity in the map and Ω is the ...

  16. Is Entrepreneurship a Route Out of Deprivation?

    DEFF Research Database (Denmark)

    Frankish, Julian S.; Roberts, Richard G.; Coad, Alexander Jean-Luc

    2014-01-01

    Frankish J. S., Roberts R. G., Coad A. and Storey D. J. Is entrepreneurship a route out of deprivation?, Regional Studies. This paper investigates whether entrepreneurship constitutes a route out of deprivation for those living in deprived areas. The measure of income/wealth used is based...... on an analysis of improvements in an individual's residential address. The data consist of information on over 800 000 individuals, and come from the customer records of a major UK bank. Comparing business owners with non-owners, the results suggest that the benefits of business ownership are found across...... the wealth distribution. Hence, entrepreneurship can be a route out of deprivation....

  17. SLEEP DEPRIVATION INDUCED ANXIETY AND ANAEROBIC PERFORMANCE

    Directory of Open Access Journals (Sweden)

    Selma Arzu Vardar

    2007-12-01

    Full Text Available The aim of this study was to investigate the effects of sleep deprivation induced anxiety on anaerobic performance. Thirteen volunteer male physical education students completed the Turkish version of State Anxiety Inventory and performed Wingate anaerobic test for three times: (1 following a full-night of habitual sleep (baseline measurements, (2 following 30 hours of sleep deprivation, and (3 following partial-night sleep deprivation. Baseline measurements were performed the day before total sleep deprivation. Measurements following partial sleep deprivation were made 2 weeks later than total sleep deprivation measurements. State anxiety was measured prior to each Wingate test. The mean state anxiety following total sleep deprivation was higher than the baseline measurement (44.9 ± 12.9 vs. 27.6 ± 4.2, respectively, p = 0.02 whereas anaerobic performance parameters remained unchanged. Neither anaerobic parameters nor state anxiety levels were affected by one night partial sleep deprivation. Our results suggest that 30 hours continuous wakefulness may increase anxiety level without impairing anaerobic performance, whereas one night of partial sleep deprivation was ineffective on both state anxiety and anaerobic performance

  18. Nonsteroidal mycotoxin alternariol is a full androgen agonist in the yeast reporter androgen bioassay.

    Science.gov (United States)

    Stypuła-Trębas, Sylwia; Minta, Maria; Radko, Lidia; Jedziniak, Piotr; Posyniak, Andrzej

    2017-10-01

    Alternariol (AOH) is a toxic metabolite of phytopathogenic fungi of the Alternaria spp. and important contaminant of agricultural commodities. According to the recent studies, AOH has a potential to modulate the endocrine system of humans and animals. In the view of these reports, our study addressed the effects of AOH on human estrogen receptor (hERα) and androgen receptor (hAR) signaling with the use of the yeast estrogen and androgen reporter bioassays. Our results show that, apart from a weak estrogenic response, AOH induces full androgenic response of the bioassay with the EC50 of 269.4μM. The androgenic potency of AOH relative to testosterone (T) is 0.046%. Moreover, in the presence of T, AOH at 5μM acts as a weak antiandrogen, whereas at higher concentrations AOH sum up with the androgenic activity of T in a dose-dependent manner, suggesting additive effect. To our knowledge it is the first report of the androgenic potency of natural, nonsteroidal substance and may have the impact on the direction of the further studies. Further research is warranted to clarify the role of AOH in disruption of AR signaling in humans and animals. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Androgen receptor signaling is required for androgen-sensitive human prostate cancer cell proliferation and survival

    Directory of Open Access Journals (Sweden)

    Day Wanda V

    2005-04-01

    Full Text Available Abstract Background Androgens and androgen receptors (AR regulate normal prostate development and growth. They also are involved in pathological development of prostatic diseases, including benign prostatic hyperplasia (BPH and prostate cancer (PCa. Antiandrogen therapy for PCa, in conjunction with chemical or surgical castration, offers initial positive responses and leads to massive prostate cell death. However, cancer cells later appear as androgen-independent PCa. To investigate the role of AR in prostate cell proliferation and survival, we introduced a vector-based small interfering RNA (siRNA. This siRNA targeted 5'-untranslated region of AR mRNA for extended suppression of AR expression in androgen-sensitive human prostate LNCaP cells. Results The siRNA design successfully suppressed endogenous AR expression, as revealed by western blotting and immunofluorescence staining in LNCaP cells. LNCaP cells did not proliferate in the absence of AR and underwent apoptosis, based on elevated phospho-Histone H2B expression and higher number of apoptotic body as compared to control cells. Conclusion We demonstrated that AR is vital for prostate cell proliferation and survival in this androgen-sensitive prostate cell line. These results further strengthen the hypothesis that AR can be a therapeutic target for treating androgen-sensitive stages of PCa. Unlike antiandorgens, however, siRNA targeting AR provides a direct inactivation of AR function through the suppression of AR protein expression.

  20. Three siblings with complete androgen insensitivity syndrome ...

    African Journals Online (AJOL)

    A diagnosis of complete androgen insensitivity syndrome was made, based on this clinical picture and laboratory findings. Two of her younger siblings were subsequently also diagnosed with this condition. She underwent an orchidectomy and is currently on female hormone replacement therapy. At the time of writing up ...

  1. Sexual behavior reduces hypothalamic androgen receptor immunoreactivity

    NARCIS (Netherlands)

    Fernandez-Guasti, Alonso; Swaab, Dick; Rodríguez-Manzo, Gabriela

    2003-01-01

    Male sexual behavior is regulated by limbic areas like the medial preoptic nucleus (MPN), the bed nucleus of the stria terminalis (BST), the nucleus accumbens (nAcc) and the ventromedial hypothalamic nucleus (VMN). Neurons in these brain areas are rich in androgen receptors (AR) and express

  2. Therapeutic Use of Androgens in Women

    Science.gov (United States)

    ... in men, the same is not true for women. Media stories about how testosterone increases libido (sexual desire) ... medications, do have lower androgen levels than healthy women. In addition, despite claims in the popular media that getting testosterone levels checked is “a small ...

  3. Leverpatologi associeret med anaboliske-androgene steroider

    DEFF Research Database (Denmark)

    Søe, Katrine; Søe, Martin Jensen; Gluud, C N

    1994-01-01

    This review regards the liver damaging side-effects of anabolic-androgenic steroids (AAS). It seems that AAS can cause development of peliosis hepatis, subcellular changes of hepatocytes, hepatocellular hyperplasia and hepatocellular adenomas. On the other hand, it has not been convincingly proved...

  4. The relationship between follicular fluid androgen concentrations ...

    African Journals Online (AJOL)

    Polycystic ovary syndrome (PCOS) is the most common cause of oligoanovulation, infertility, and hyperandrogenism in women and characterized by abnormal folliculogenesis. The androgen receptoe ( AR) is present in the ovary in almost all stages of folliculogenesis and has been suggested to play a proliferative role for ...

  5. Development of selective androgen receptor modulators (SARMs).

    Science.gov (United States)

    Narayanan, Ramesh; Coss, Christopher C; Dalton, James T

    2017-06-15

    The Androgen Receptor (AR), a member of the steroid hormone receptor family, plays important roles in the physiology and pathology of diverse tissues. AR ligands, which include circulating testosterone and locally synthesized dihydrotestosterone, bind to and activate the AR to elicit their effects. Ubiquitous expression of the AR, metabolism and cross reactivity with other receptors limit broad therapeutic utilization of steroidal androgens. However, the discovery of selective androgen receptor modulators (SARMs) and other tissue-selective nuclear hormone receptor modulators that activate their cognate receptors in a tissue-selective manner provides an opportunity to promote the beneficial effects of androgens and other hormones in target tissues with greatly reduced unwanted side-effects. In the last two decades, significant resources have been dedicated to the discovery and biological characterization of SARMs in an effort to harness the untapped potential of the AR. SARMs have been proposed as treatments of choice for various diseases, including muscle-wasting, breast cancer, and osteoporosis. This review provides insight into the evolution of SARMs from proof-of-concept agents to the cusp of therapeutic use in less than two decades, while covering contemporary views of their mechanisms of action and therapeutic benefits. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Deciphering the selective androgen receptor modulators paradigm.

    Science.gov (United States)

    Zhang, Xuqing; Sui, Zhihua

    2013-02-01

    The development and potential clinical use of tissue-selective androgen receptor modulators (SARMs) have advanced tremendously over the past few years. A key aspect of SARMs is the ability to clearly differentiate between the anabolic and androgenic activities. SARMs provide therapeutic opportunities in a variety of diseases, including muscle wasting associated with burns, cancer, end-stage renal disease, osteoporosis, frailty and hypogonadism. The aim of the present paper is to summarize the current standing of research and development of SARMs and plausible molecular mechanisms underlying the potential for selective modulation of androgen receptor (AR) by different ligands. This paper also provides an update on SARM discovery paradigms for preclinical evaluations. Promising results have been obtained in preclinical investigations and initial clinical trials, but long-term safety, tolerability and efficacy studies in patients are still necessary. Preclinically, improving knowledge of tissue selectivity at the molecular level, developing AR selectivity transcription profile, exploring in vitro/in vivo correlation, along with expanding selectivity evaluation among more androgen responsive tissues would accelerate the discovery of a new generation of more selective and safer clinical candidates, minimize false leads and hasten development of effective approaches for an expanded range of clinical conditions.

  7. Cosmic Rays in Intermittent Magnetic Fields

    Energy Technology Data Exchange (ETDEWEB)

    Shukurov, Anvar; Seta, Amit; Bushby, Paul J.; Wood, Toby S. [School of Mathematics and Statistics, Newcastle University, Newcastle Upon Tyne NE1 7RU (United Kingdom); Snodin, Andrew P., E-mail: a.seta1@ncl.ac.uk, E-mail: amitseta90@gmail.com [Department of Mathematics, Faculty of Applied Science, King Mongkut’s University of Technology North Bangkok, Bangkok 10800 (Thailand)

    2017-04-10

    The propagation of cosmic rays in turbulent magnetic fields is a diffusive process driven by the scattering of the charged particles by random magnetic fluctuations. Such fields are usually highly intermittent, consisting of intense magnetic filaments and ribbons surrounded by weaker, unstructured fluctuations. Studies of cosmic-ray propagation have largely overlooked intermittency, instead adopting Gaussian random magnetic fields. Using test particle simulations, we calculate cosmic-ray diffusivity in intermittent, dynamo-generated magnetic fields. The results are compared with those obtained from non-intermittent magnetic fields having identical power spectra. The presence of magnetic intermittency significantly enhances cosmic-ray diffusion over a wide range of particle energies. We demonstrate that the results can be interpreted in terms of a correlated random walk.

  8. Prolonged Intermittent Renal Replacement Therapy.

    Science.gov (United States)

    Edrees, Fahad; Li, Tingting; Vijayan, Anitha

    2016-05-01

    Prolonged intermittent renal replacement therapy (PIRRT) is becoming an increasingly popular alternative to continuous renal replacement therapy in critically ill patients with acute kidney injury. There are significant practice variations in the provision of PIRRT across institutions, with respect to prescription, technology, and delivery of therapy. Clinical trials have generally demonstrated that PIRRT is non-inferior to continuous renal replacement therapy regarding patient outcomes. PIRRT offers cost-effective renal replacement therapy along with other advantages such as early patient mobilization and decreased nursing time. However, due to lack of standardization of the procedure, PIRRT still poses significant challenges, especially pertaining to appropriate drug dosing. Future guidelines and clinical trials should work toward developing consensus definitions for PIRRT and ensure optimal delivery of therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  9. Characteristics of intermittent fuel sprays

    Science.gov (United States)

    Jawad, B.; Gulari, E.; Henein, N. A.

    1992-03-01

    The spray-tip penetrations and the drop sizes of intermittent fuel sprays were measured by using a modified pulsed optical spray sizer. The average spray tip speeds were determined from simultaneously recorded needle lift signals and obscuration traces. The speeds of a sequence of fuel pulses injected at about 1000 Hz were analyzed to elucidate penetration mechanisms. A correlation that relates penetration distance to time, pressure drop across the nozzle, fuel density, and ambient gas density was obtained. The temporal variations of drop size in penetrating pulses of sprays were measured. The concentration of drops were calculated by combining drop size and obscuration data. The Sauter mean diameter of penetrating fuel drops increased with an increase of the chamber pressure and decreased with an increase of the injection pressure.

  10. Ginkgo biloba for intermittent claudication.

    Science.gov (United States)

    Nicolaï, Saskia P A; Kruidenier, Lotte M; Bendermacher, Bianca L W; Prins, Martin H; Stokmans, Rutger A; Broos, Pieter P H L; Teijink, Joep A W

    2013-06-06

    People with intermittent claudication (IC) suffer from pain in the muscles of the leg occurring during exercise which is relieved by a short period of rest. Symptomatic relief can be achieved by (supervised) exercise therapy and pharmacological treatments. Ginkgo biloba is a vasoactive agent and is used to treat IC. To assess the effect of Ginkgo biloba on walking distance in people with intermittent claudication. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (March 2013) and CENTRAL (2013, Issue 2). Randomised controlled trials of Ginkgo biloba extract, irrespective of dosage, versus placebo in people with IC. Two authors independently assessed trials for selection, assessed study quality and extracted data. We extracted number of patients, mean walking distances or times and standard deviations. To standardise walking distance or time, caloric expenditures were used to express the difference between the different treadmill protocols, which were calculated from the speed and incline of the treadmill. Fourteen trials with a total of 739 participants were included. Eleven trials involving 477 participants compared Ginkgo biloba with placebo and assessed the absolute claudication distance (ACD). Following treatment with Ginkgo biloba at the end of the study the ACD increased with an overall effect size of 3.57 kilocalories (confidence interval (CI) -0.10 to 7.23, P = 0.06), compared with placebo. This translates to an increase of just 64.5 ( CI -1.8 to 130.7) metres on a flat treadmill with an average speed of 3.2 km/h. Publication bias leading to missing data or "negative" trials is likely to have inflated the effect size. Overall, there is no evidence that Ginkgo biloba has a clinically significant benefit for patients with peripheral arterial disease.

  11. Relative deprivation and political protest

    Directory of Open Access Journals (Sweden)

    R. M. Kliuchnyk

    2017-03-01

    Examples of anti-system political parties and movements have been given. Many of them have changed the political disposition in Europe. Lega Nord (Italy, PEGIDA (Germany, Movimento 5 Stelle (Italy, Front National (France, Ataka (Bulgaria, etc are between them. These parties and movements influence increasingly on the European political process. Nativism and populism are marked as main peculiarities of such right parties. According to the author, Anti-Trump protests in the USA are the examples of the relative deprivation of numerous groups of people that feel their rights and freedoms being threatened.

  12. Androgen Receptor Expression in Primary Nonsquamous Cell Rare-Variant Carcinomas of the Head and Neck

    Directory of Open Access Journals (Sweden)

    Siavash Rahimi MD, FRCPath

    2017-06-01

    Full Text Available Objective Androgen receptor (AR is a diagnostic immunohistochemical marker for salivary gland duct carcinoma (SDC, but other nonsquamous cell head and neck carcinomas (NSCCs may also express it. The aim of this preliminary study was to investigate the immunohistochemical expression of AR in rare head and neck NSCCs. Study Design Retrospective analysis of histologic records. Setting A large community hospital. Subjects and Methods Twenty-seven patients with NSCC were selected (21 men, 6 women; average age, 69 years. Exclusion criteria were histologically confirmed primary and metastatic head and neck squamous cell carcinomas and thyroid carcinomas. AR immunohistochemistry was done on formalin-fixed, paraffin-embedded tissue blocks. Results Variable AR expression was found in 5 of 27 (25% cases of NSCC. All 7 patients with SDC showed intense and extensive positive immunoreactivity. Of 27 NSCC tumors, 15 (56% had negative staining. Conclusion In the head and neck, expression of AR is not limited to SDCs; other NSCCs also express it. When surgery or radiotherapy is not appropriate for recurrent or metastatic head and neck NSCC, palliative chemotherapy offers poor results. Antiandrogen therapy is well tolerated and is much less toxic than chemotherapy. Since androgen deprivation therapy has been used against SDCs, this therapy may theoretically be used in a small subset of head and neck NSCCs.

  13. Origin of Androgen-Insensitive Poorly Differentiated Tumors in the Transgenic Adenocarcinoma of Mouse Prostate Model

    Directory of Open Access Journals (Sweden)

    Wendy J. Huss

    2007-11-01

    Full Text Available Following castration, the transgenic adenocarcinoma of mouse prostate (TRAMP model demonstrates rapid development of SV40-Tag-driven poorly differentiated tumors that express neuroendocrine cell markers. The cell population dynamics within the prostates of castrated TRAMP mice were characterized by analyzing the incorporation of 5-bromodeoxyuridine (BrdUrd and the expression of SV40-Tag, synaptophysin, and androgen receptor (AR. Fourteen days postcastration, the remaining epithelial cells and adenocarcinoma cells were nonproliferative and lacked detectable SV40-Tag or synaptophysin expression. In contrast, morphologically distinct intraglandular foci were identified which expressed SV40-Tag, synaptophysin, and Ki67, but that lacked AR expression. These proliferative SV40-Tag and synaptophysin-expressing intraglandular foci were associated with the rare BrdUrd-retaining cells. These foci expanded rapidly in the postcastration prostate environment, in contrast to the AR- and SV40-Tag-expressing adenocarcinoma cells that lost SV40-Tag expression and underwent apoptosis after castration. Intraglandular foci of synaptophysin-expressing cells were also observed in the prostates of intact TRAMP mice at a comparable frequency; however, they did not progress to rapidly expanding tumors until much later in the life of the mice. This suggests that the foci of neuroendocrine-like cells that express SV40-Tag and synaptophysin, but lack AR, arise independent of androgen-deprivation and represent the source of the poorly differentiated tumors that are the lethal phenotype in the TRAMP model.

  14. Effect of monocular deprivation on rabbit neural retinal cell densities

    Directory of Open Access Journals (Sweden)

    Philip Maseghe Mwachaka

    2015-01-01

    Conclusion: In this rabbit model, monocular deprivation resulted in activity-dependent changes in cell densities of the neural retina in favour of the non-deprived eye along with reduced cell densities in the deprived eye.

  15. Identification of a RhoA- and SRF-dependent mechanism of androgen action that is associated with prostate cancer progression.

    Science.gov (United States)

    Heemers, Hannelore V

    2013-04-01

    Androgen receptor (AR) action is critical for prostate cancer (CaP) progression, but is not inhibited fully by available androgen deprivation therapy (ADT). One of the limitations to current ADT is that it targets all androgen action in CaP, and other, cells irrespective of clinical relevance. The resulting off-target effects are responsible for ADT associated side effects that affect negatively a patient's quality of life. Isolation of the AR-dependent events that drive CaP progression may lead to novel forms of ADT that are at least as effective but more selective. Here, an approach is described that starts from insights in the basic mechanism(s) by which AR regulates target gene expression to identify novel drugable targets downstream of AR. Exploration of the molecular events that underlie androgen regulation of the AR-associated coregulator FHL2 led to the isolation of a novel indirect mechanism of androgen action that is mediated by the secondary transcription factor Serum Response Factor (SRF). Using a combination of oligoarray and in silico analyses, an SRF-dependent fraction of AR action was identified that is enriched in CaP tissues, is able to discriminate between benign and malignant prostate, and correlates with aggressive disease and biochemical failure. The RhoA signaling axis, a well known upstream stimulator of SRF action that harbors drugable targets, conveyed androgen-responsiveness to SRF, and was activated in CaP where it correlates with increased CaP aggressiveness and poor outcome after surgery.

  16. Sleep Deprivation and the Epigenome.

    Science.gov (United States)

    Gaine, Marie E; Chatterjee, Snehajyoti; Abel, Ted

    2018-01-01

    Sleep deprivation disrupts the lives of millions of people every day and has a profound impact on the molecular biology of the brain. These effects begin as changes within a neuron, at the DNA and RNA level, and result in alterations in neuronal plasticity and dysregulation of many cognitive functions including learning and memory. The epigenome plays a critical role in regulating gene expression in the context of memory storage. In this review article, we begin by describing the effects of epigenetic alterations on the regulation of gene expression, focusing on the most common epigenetic mechanisms: (i) DNA methylation; (ii) histone modifications; and (iii) non-coding RNAs. We then discuss evidence suggesting that sleep loss impacts the epigenome and that these epigenetic alterations might mediate the changes in cognition seen following disruption of sleep. The link between sleep and the epigenome is only beginning to be elucidated, but clear evidence exists that epigenetic alterations occur following sleep deprivation. In the future, these changes to the epigenome could be utilized as biomarkers of sleep loss or as therapeutic targets for sleep-related disorders.

  17. Sleep Deprivation and the Epigenome

    Directory of Open Access Journals (Sweden)

    Marie E. Gaine

    2018-02-01

    Full Text Available Sleep deprivation disrupts the lives of millions of people every day and has a profound impact on the molecular biology of the brain. These effects begin as changes within a neuron, at the DNA and RNA level, and result in alterations in neuronal plasticity and dysregulation of many cognitive functions including learning and memory. The epigenome plays a critical role in regulating gene expression in the context of memory storage. In this review article, we begin by describing the effects of epigenetic alterations on the regulation of gene expression, focusing on the most common epigenetic mechanisms: (i DNA methylation; (ii histone modifications; and (iii non-coding RNAs. We then discuss evidence suggesting that sleep loss impacts the epigenome and that these epigenetic alterations might mediate the changes in cognition seen following disruption of sleep. The link between sleep and the epigenome is only beginning to be elucidated, but clear evidence exists that epigenetic alterations occur following sleep deprivation. In the future, these changes to the epigenome could be utilized as biomarkers of sleep loss or as therapeutic targets for sleep-related disorders.

  18. Neurocognitive consequences of sleep deprivation.

    Science.gov (United States)

    Goel, Namni; Rao, Hengyi; Durmer, Jeffrey S; Dinges, David F

    2009-09-01

    Sleep deprivation is associated with considerable social, financial, and health-related costs, in large measure because it produces impaired cognitive performance due to increasing sleep propensity and instability of waking neurobehavioral functions. Cognitive functions particularly affected by sleep loss include psychomotor and cognitive speed, vigilant and executive attention, working memory, and higher cognitive abilities. Chronic sleep-restriction experiments--which model the kind of sleep loss experienced by many individuals with sleep fragmentation and premature sleep curtailment due to disorders and lifestyle--demonstrate that cognitive deficits accumulate to severe levels over time without full awareness by the affected individual. Functional neuroimaging has revealed that frequent and progressively longer cognitive lapses, which are a hallmark of sleep deprivation, involve distributed changes in brain regions including frontal and parietal control areas, secondary sensory processing areas, and thalamic areas. There are robust differences among individuals in the degree of their cognitive vulnerability to sleep loss that may involve differences in prefrontal and parietal cortices, and that may have a basis in genes regulating sleep homeostasis and circadian rhythms. Thus, cognitive deficits believed to be a function of the severity of clinical sleep disturbance may be a product of genetic alleles associated with differential cognitive vulnerability to sleep loss. Thieme Medical Publishers.

  19. Intermittent Swimming with a Flexible Propulsor

    Science.gov (United States)

    Akoz, Emre; Moored, Keith

    2017-11-01

    Aquatic animals use a variety of swimming gaits to propel themselves efficiently through the oceans. One type of gait known as intermittent or burst-and-coast swimming is used by species such as saithe, cod and trout. Recent studies have shown that this gait can save up to 60% of a swimmer's energy by exploiting an inviscid Garrick mechanism. These detailed studies have examined the effects of an intermittent swimming gait on rigid propulsors, yet the caudal fins of intermittent swimmers are in fact highly flexible propulsors. In this respect, to gain a comprehensive understanding of intermittent swimming, the effect of elasticity on the swimming performance and wake flow of an intermittent swimmer is investigated. To accomplish this a torsional spring structural model is strongly coupled to a fast boundary element method solver that captures the fluid-structure interaction of a two-dimensional self-propelled intermittently pitching hydrofoil. It is shown that flexibility introduces extra vortices to the coasting phase of motion that can either promote or diminish thrust production depending upon the hydrofoil parameters. An optimal intermittent flexible swimmer is shown to increase its efficiency by as much as 28% when compared to an optimal continuous flexible swimmer. Supported by the Office of Naval Research under Program Director Dr. Bob Brizzolara, MURI Grant Number N00014-14-1-0533.

  20. Specific modulation of nongenomic androgen signaling in the ovary.

    Science.gov (United States)

    White, Stacy N; Jamnongjit, Michelle; Gill, Arvind; Lutz, Lindsey B; Hammes, Stephen R

    2005-01-01

    Maturation, or meiotic progression, of amphibian oocytes is one of the few physiologically relevant steroid-mediated processes that occurs in the complete absence of transcription from beginning to end. As such, frog oocyte maturation has served as a useful model of nongenomic steroid signaling for many years. Earlier work in Xenopus laevis demonstrated that, although several steroids promoted oocyte maturation in vitro, androgens were the most abundant and potent steroids detected in the serum and ovaries of ovulating frogs. Thus, androgens were likely the primary physiologic regulators of Xenopus oocyte maturation, mediating their actions at least in part via classical androgen receptors expressed in oocytes. The importance of androgens for Xenopus oocyte maturation and ovulation has now been confirmed, as inhibition of androgen production in vivo by blocking CYP17 activity reduced hCG-triggered oocyte maturation and delayed ovulation in female frogs. Taking advantage of the absolute transcription-independence of this androgen-mediated response, selective androgen receptor modulators (SARMs) have been characterized that specifically promote genomic versus nongenomic androgen responses. These include androstenediol and estren, which preferentially promote nongenomic signals, as well as R1881 and 19-nortestosterone, which preferentially promote genomic signaling. Interestingly, the SARMs androstenediol and R1881 signal similarly in mouse oocytes, demonstrating the conserved nature of androgen-mediated maturation in vertebrates. These results suggest that SARMs may serve as useful tools for specifically regulating nongenomic androgen signaling both in vitro and in vivo.

  1. Physiological responses of men during sleep deprivation.

    Science.gov (United States)

    1970-05-01

    The effects of 84 hours of sleep deprivation were examined in a group of six young men and compared with a group of six controls. Subjects were studied in pairs, one sleep-deprived and one control. Primary attention was given to the responses to acut...

  2. Motor development after vestibular deprivation in rats

    NARCIS (Netherlands)

    Geisler, HC; Gramsbergen, A

    This review summarizes the postural development in the rat and the influences of vestibular deprivation from the 5th postnatal day on this development. Vestibular deprivation leads to a delay in motor development. Most probably this delay is caused by a delay in the development of postural control,

  3. Health-risk behaviour in deprived neighbourhoods compared with non-deprived neighbourhoods

    DEFF Research Database (Denmark)

    Algren, Maria Holst; Bak, Carsten Kronborg; Berg-Beckhoff, Gabriele

    2015-01-01

    in deprived neighbourhoods compared with those who live in non-deprived neighbourhoods and to summarise what kind of operationalisations of neighbourhood deprivation that were used in the studies. METHODS: PRISMA guidelines for systematic reviews were followed. Systematic searches were performed in Pub......Med, Embase, Web of Science and Sociological Abstracts using relevant search terms, Boolean operators, and truncation, and reference lists were scanned. Quantitative observational studies that examined health-risk behaviour in deprived neighbourhoods compared with non-deprived neighbourhoods were eligible...... consumption, the results were ambiguous, and no clear differences were found. Numerous different operationalisations of neighbourhood deprivation were used in the studies. CONCLUSION: Substantial evidence indicates that future health interventions in deprived neighbourhoods should focus on smoking...

  4. Assessing Relative Volatility/Intermittency/Energy Dissipation

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole E.; Pakkanen, Mikko; Schmiegel, Jürgen

    process in particular. While this estimation method is motivated by the assessment of relative energy dissipation in empirical data of turbulence, we apply it also to energy price data. Moreover, we develop a probabilistic asymptotic theory for relative power variations of Brownian semistationary......We introduce the notion of relative volatility/intermittency and demonstrate how relative volatility statistics can be used to estimate consistently the temporal variation of volatility/intermittency even when the data of interest are generated by a non-semimartingale, or a Brownian semistationary...... processes and Ito semimartingales and discuss how it can be used for inference on relative volatility/intermittency....

  5. Intermittent cranial lung herniation in two dogs.

    Science.gov (United States)

    Guglielmini, Carlo; De Simone, Antonio; Valbonetti, Luca; Diana, Alessia

    2007-01-01

    Two aged dogs with chronic obstructive airway disease were evaluated because of intermittent swelling of the ventral cervical region. Radiographs made at expiration and caudal positioning of the forelimbs allowed identification of intermittent cervical lung herniation of the left and right cranial lung lobe in both dogs. Pulmonary hyperinflation, increased expiratory effort, and chronic coughing were considered responsible for the lung herniation. Cervical lung hernia should be included in the differential diagnoses of intermittent cervical swelling in dogs with chronic respiratory disorders associated with increased expiratory effort and chronic coughing.

  6. Sleep deprivation suppresses aggression in Drosophila

    Science.gov (United States)

    Kayser, Matthew S; Mainwaring, Benjamin; Yue, Zhifeng; Sehgal, Amita

    2015-01-01

    Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness. DOI: http://dx.doi.org/10.7554/eLife.07643.001 PMID:26216041

  7. Lenses generated by intermittent currents

    Science.gov (United States)

    Nof, Doron

    1991-03-01

    A nonlinear mechanism for the generation of anticyclonic lens-like eddies from boundary currents is proposed. In contrast to the familiar generation processes that rely on unstable long waves that grow and close upon themselves or vortex shedding due to the geometry of the boundary, the present mechanism is related to intermittency in the current's mass transport. The essence of the new mechanism is that intermittencies in the transport (such as those in the Denmark Strait or the Mediterranean outflow) lead to unbalanced patches of fluid which break up into a discrete sets of eddies that interact with the boundary. The process is highly nonlinear because both the amplitude and the Rossby number are of order unity. It is modeled as follows: we begin with a rectangular box containing the motionless (light) fluid near the boundary. At, say, t = 0, the conceptual box is removed the unbalanced fluid undergoes two main processes. The first involves the establishment of a set of eddies via breakup and geostrophic adjustment, whereas the second is associated with the interaction of the set with the wall. These two processes are examined independently even though in reality the processes are, obviously, taking place at the same time. To examine the first processes we consider the nonlinear collapse of a (light) rectangular box in the open ocean away from the boundary. The breakup processes involves, of course, some sort of instability (because the patch does not remain intact) but this is not necessarily related to the long wave instability that is usually associated with long gravity currents. The general structures of the resulting final chain of eddies can be computed analytically by using the usual connecting principles, the conservation of potential vorticity and mass. It turns out, however, that the number of eddies and their detailed structure cannot be computed unless one invokes an additional constraint. To resolve this closure difficulty, the integrated angular

  8. Lifestyle intervention program in deprived obese adult patients and their non-deprived counterparts.

    Science.gov (United States)

    Loddo, Celine; Pupier, Emilie; Amour, Rémy; Monsaingeon-Henry, Maud; Mohammedi, Kamel; Gatta-Cherifi, Blandine

    2017-01-01

    Although it is known that the prevalence of obesity is high in deprived patients, the link between deprivation and obesity, and the impact of deprivation on compliance and efficacy of a lifestyle intervention program are not known. Deprivation was assessed in 40 patients (23 Females, mean±SD age: 49±17 years) from the diabetology department and 140 patients (101 Females, age: 50±15 years) from the nutrition department of Bordeaux University hospital. Eighty-seven patients suffering from obesity were evaluated before and after a tailored, multidisciplinary lifestyle intervention. Deprivation was assessed using EPICES scores. Deprivation was defined with an EPICES score > 30. Deprived patients suffering from obesity had significantly higher current (43.8 ±8.4 versus 40.9 ± 5.5 kg/m2, p = 0,02) and maximal BMI (46.1± 8.6 versus 42.3± 5.2 kg/m2, p = 0.002) compared to non-deprived obese. Percentage of body weight loss was not different according to deprivation (4.74 ± 0.75 versus 4.65 ± 1.04%, p = 0.9). EPICES scores were not different according to adherence to lifestyle intervention program (20.5 ± 8.5 versus 29.9 ± 3.9 versus 29.0 ±2.5, no follow up versus partial follow up versus total follow up, p = 0,58). Deprived patients suffering from obesity have a more serious disease than non-deprived patients. However, neither compliance to the lifestyle intervention program nor body weight loss differed between deprived patients with obesity and non-deprived ones. Deprivation should not be a limitation when enrolling patients with obesity in lifestyle intervention programs.

  9. Lifestyle intervention program in deprived obese adult patients and their non-deprived counterparts.

    Directory of Open Access Journals (Sweden)

    Celine Loddo

    Full Text Available Although it is known that the prevalence of obesity is high in deprived patients, the link between deprivation and obesity, and the impact of deprivation on compliance and efficacy of a lifestyle intervention program are not known.Deprivation was assessed in 40 patients (23 Females, mean±SD age: 49±17 years from the diabetology department and 140 patients (101 Females, age: 50±15 years from the nutrition department of Bordeaux University hospital. Eighty-seven patients suffering from obesity were evaluated before and after a tailored, multidisciplinary lifestyle intervention. Deprivation was assessed using EPICES scores. Deprivation was defined with an EPICES score > 30.Deprived patients suffering from obesity had significantly higher current (43.8 ±8.4 versus 40.9 ± 5.5 kg/m2, p = 0,02 and maximal BMI (46.1± 8.6 versus 42.3± 5.2 kg/m2, p = 0.002 compared to non-deprived obese. Percentage of body weight loss was not different according to deprivation (4.74 ± 0.75 versus 4.65 ± 1.04%, p = 0.9. EPICES scores were not different according to adherence to lifestyle intervention program (20.5 ± 8.5 versus 29.9 ± 3.9 versus 29.0 ±2.5, no follow up versus partial follow up versus total follow up, p = 0,58.Deprived patients suffering from obesity have a more serious disease than non-deprived patients. However, neither compliance to the lifestyle intervention program nor body weight loss differed between deprived patients with obesity and non-deprived ones. Deprivation should not be a limitation when enrolling patients with obesity in lifestyle intervention programs.

  10. Extended access nicotine self-administration with periodic deprivation increases immature neurons in the hippocampus.

    Science.gov (United States)

    Cohen, Ami; Soleiman, Matthew T; Talia, Reneta; Koob, George F; George, Olivier; Mandyam, Chitra D

    2015-01-01

    Limited access nicotine self-administration decreases hippocampal neurogenesis, providing a mechanism for the deleterious effects of nicotine on hippocampal neuronal plasticity. However, recent studies have shown that limited access nicotine self-administration does not exhibit key features of nicotine dependence such as motivational withdrawal and increased motivation for nicotine after deprivation. The present study used extended access nicotine self-administration (0.03 mg/kg/infusion, 21 h/day, 4 days) with intermittent periods of deprivation (3 days) for 14 weeks, to test the hypothesis that this model enhances nicotine seeking and produces distinct responses in hippocampal neurogenesis when compared with limited access (1 h/day, 4 days) intake. Animals in the extended access group were either perfused prior to or following their final deprivation period, whereas animals in the limited access group were perfused after their last session. Limited- and extended access nicotine self-administration with periodic deprivation did not affect proliferation and differentiation of oligodendrocyte progenitors in the medial prefrontal cortex (mPFC). Conversely, extended access nicotine self-administration with periodic deprivation enhanced proliferation and differentiation of hippocampal neural progenitors. Furthermore, in the hippocampus, the number of differentiating NeuroD-labeled cells strongly and positively correlated with enhanced nicotine seeking in rats that experienced extended access nicotine self-administration. These findings demonstrate that extended versus limited access to nicotine self-administration differentially affects the generation of new oligodendroglia and new neurons during adulthood. The increases in the number of differentiating cells in extended access nicotine self-administering rats may consequently contribute to aberrant hippocampal neurogenesis and may contribute to maladaptive addiction-like behaviors dependent on the hippocampus.

  11. Effect of Intermittent Feeding on Gonadal Function in Male And Female NMRI Mice During Chronic Stress

    Directory of Open Access Journals (Sweden)

    Badri Zarrin Ehteram

    2017-10-01

    Full Text Available ABSTRACT Stress can inhibit gonadal activity via Hypothalamus-Pituitary-Gonad (HPG axis activity suppression. In the present study, effects of intermittent feeding (IF on gonadal function under stress in male and female mice were evaluated. Twenty eight male and twenty eight female mice's were divided into four groups. The control group received adequate food and water without stress. The second group received four days of electric shock without food deprivation. The third group was deprived of food two hours/day for a week, and the fourth group was deprived of food (2 hours/day for seven consecutive days and then electric foot shock stress was applied to them for four days. Blood samples were collected from all animals for plasma testosterone, estrogen and/or Interlukin-6 (IL-6 evaluation. The animals’ gonads were also removed and fixed for the measure of their weight. Results showed that stress reduces both testosterone and estrogen levels, whereas IF did not change the hormone levels. In addition, stress increases blood IL-6 concentration. The combination of IF and stress, increased the hormone levels in animals. Stress and IF alone had no significant effect on gonadal weight in the male mice, whereas stress decreased gonadal weight in the females. Combination of stress with IF increased gonadal weight in both male and female mice. In conclusion stress showed a negative effect on gonadal function in both animals with more effect on females. Intermittent feeding inhibits the stress effect and even promotes the gonadal function in both sexes. The effect may be due to IL-6 reduction.

  12. The Androgen Receptor Gene Mutations Database.

    Science.gov (United States)

    Gottlieb, B; Lehvaslaiho, H; Beitel, L K; Lumbroso, R; Pinsky, L; Trifiro, M

    1998-01-01

    The current version of the androgen receptor (AR) gene mutations database is described. The total number of reported mutations has risen from 272 to 309 in the past year. We have expanded the database: (i) by giving each entry an accession number; (ii) by adding information on the length of polymorphic polyglutamine (polyGln) and polyglycine (polyGly) tracts in exon 1; (iii) by adding information on large gene deletions; (iv) by providing a direct link with a completely searchable database (courtesy EMBL-European Bioinformatics Institute). The addition of the exon 1 polymorphisms is discussed in light of their possible relevance as markers for predisposition to prostate or breast cancer. The database is also available on the internet (http://www.mcgill. ca/androgendb/ ), from EMBL-European Bioinformatics Institute (ftp. ebi.ac.uk/pub/databases/androgen ), or as a Macintosh FilemakerPro or Word file (MC33@musica.mcgill.ca).

  13. Sky dancer: an intermittent system

    Science.gov (United States)

    Cros, Anne; Rodríguez Romero, Jesse Alexander; Damián Díaz Andrade, Oscar

    2009-11-01

    Sky dancers attract people sight to make advertising. What is the origin of those large vertical tubes fluctuations above an air blower? This study complements the previous one [1] about the system analysis from a dynamical system point of view. As a difference from the ``garden hose-instability'' [2], the tube shape has got ``break points''. Those ``break points'' separate the air-filled bottom tube portion from its deflated top portion. We record the tube dynamics with a high-speed videocamera simultaneously that we measure the pressure at the air blower exit. The intermittent pressure evolution displays picks when the tube fluctuates. We compare those overpressure values with the ones that appears in a rigid tube whose exit is partially obstructed. [1] F. Castillo Flores & A. Cros ``Transition to chaos of a vertical collapsible tube conveying air flow'' J. Phys.: Conf. Ser. 166, 012017 (2009). [2] A. S. Greenwald & J. Dungundji ``Static and dynamic instabilities of a propellant line'' MIT Aeroelastic and Structures Research Lab, AFOSR Sci. Report: AFOSR 67-1395 (1967).

  14. Intermittent sea-level acceleration

    Science.gov (United States)

    Olivieri, M.; Spada, G.

    2013-10-01

    Using instrumental observations from the Permanent Service for Mean Sea Level (PSMSL), we provide a new assessment of the global sea-level acceleration for the last ~ 2 centuries (1820-2010). Our results, obtained by a stack of tide gauge time series, confirm the existence of a global sea-level acceleration (GSLA) and, coherently with independent assessments so far, they point to a value close to 0.01 mm/yr2. However, differently from previous studies, we discuss how change points or abrupt inflections in individual sea-level time series have contributed to the GSLA. Our analysis, based on methods borrowed from econometrics, suggests the existence of two distinct driving mechanisms for the GSLA, both involving a minority of tide gauges globally. The first effectively implies a gradual increase in the rate of sea-level rise at individual tide gauges, while the second is manifest through a sequence of catastrophic variations of the sea-level trend. These occurred intermittently since the end of the 19th century and became more frequent during the last four decades.

  15. Social Smoking among Intermittent Smokers

    Science.gov (United States)

    Shiffman, Saul; Li, Xiaoxue; Dunbar, Michael S.; Ferguson, Stuart G.; Tindle, Hilary A.; Scholl, Sarah M.

    2015-01-01

    Background “Social smoking” - smoking mostly or even only with others – may be an important pattern that implies smoking motivated extrinsically by social influences. Non-daily smokers (intermittent smokers; ITS) are often assumed to be social smokers, with some authors even assuming that all ITS are social smokers (SS+). We sought to identify and characterize social smokers in a sample of ITS. Methods 204 adult ITS (smoking 4–27 days/month) recorded the circumstances of smoking in their natural settings using Ecological Momentary Assessment, while also recording their circumstances in nonsmoking moments. SS+ were defined as ITS who were with others when they smoked most of their cigarettes, and who were ≥ 50% more likely to be with others when smoking than when not. Results Only 13% of ITS were SS+. Although defined solely on the basis of presence of others, SS+ showed a distinct pattern of smoking across multiple dimensions: Compared to other ITS (who were significantly less likely to smoke when with others), SS+ smoking was more associated with socializing, being with friends and acquaintances, drinking alcohol, weekends, evening or nighttime, being in other people’s homes, but not their own home. SS+ smoking was low in the morning and increased in the evening. SS+ smoked fewer days/week and were less dependent, but did not differ demographically. Conclusions Social smoking does constitute a highly distinct smoking pattern, but is not common among adult ITS. PMID:26205313

  16. Androgen levels in women with various forms of ovarian dysfunction : Associations with cardiometabolic features

    NARCIS (Netherlands)

    Daan, N. M P; Jaspers, L.; Koster, M. P H; Broekmans, F. J M; De Rijke, Y. B.; Franco, O. H.; Laven, J. S E; Kavousi, M.; Fauser, B. C J M

    2015-01-01

    STUDY QUESTION Are differences in androgen levels among women with various forms of ovarian dysfunction associated with cardiometabolic abnormalities? SUMMARY ANSWER Androgen levels differed substantially between women with and without ovarian dysfunction, and increased androgen levels were

  17. On-line intermittent connector anomaly detection

    Data.gov (United States)

    National Aeronautics and Space Administration — This paper investigates a non-traditional use of differential current sensor and current sensor to detect intermittent disconnection problems in connectors. An...

  18. Intermittent chaotic chimeras for coupled rotators

    DEFF Research Database (Denmark)

    Olmi, Simona; Martens, Erik Andreas; Thutupalli, Shashi

    2015-01-01

    Two symmetrically coupled populations of N oscillators with inertia m display chaotic solutions with broken symmetry similar to experimental observations with mechanical pendulums. In particular, we report evidence of intermittent chaotic chimeras, where one population is synchronized and the other...

  19. Sleep deprivation: consequences for students.

    Science.gov (United States)

    Marhefka, Julie King

    2011-09-01

    During the adolescent years, a delayed pattern of the sleep-wake cycle occurs. Many parents and health care providers are not aware that once established, these poor sleep habits can continue into adulthood. Early school hours start a pattern of sleep loss that begins a cycle of daytime sleepiness, which may affect mood, behavior, and increase risk for accidents or injury. These sleep-deprived habits established in adolescence can often lead to problems during college years. Sleep hygiene can be initiated to help break the cycle, along with education and implementation of a strict regimen. Monitoring all adolescents and college-aged students for sleep insufficiency is imperative to improve both academic and emotional well-being. Copyright 2011, SLACK Incorporated.

  20. Infantile nystagmus and visual deprivation

    DEFF Research Database (Denmark)

    Fledelius, Hans C; Jensen, Hanne

    2014-01-01

    refraction was emmetropia in all subgroups. Compared with Danish control data, myopia was over-represented, and generally of juvenile onset. The Down syndrome subgroup was separated from the remainder by an even higher myopia prevalence. Astigmatism above 1 D cylinder value was recorded in 52% of all cases......PURPOSE: To evaluate whether effects of early foveal motor instability due to infantile nystagmus might compare to those of experimental visual deprivation on refraction in a childhood series. METHODS: This was a retrospective analysis of data from the Danish Register for Blind and Weaksighted...... Children with infantile nystagmus recorded as prime diagnosis. We perused 90 records of children now aged 10-17 years, some of whom eventually exceeded the register borderline of 0.3 as best-corrected visual acuity. Spherical equivalent refraction was the primary outcome parameter, but visual acuity...

  1. Infantile nystagmus and visual deprivation

    DEFF Research Database (Denmark)

    Fledelius, Hans C; Jensen, Hanne

    2014-01-01

    . CONCLUSIONS: The prevalence of myopia and astigmatism was higher among children with nystagmus than in controls. Myopia was mainly juvenile, and not related to the period of infancy when the motor foveal smear is considered most disturbing and possibly influencing visual development.......PURPOSE: To evaluate whether effects of early foveal motor instability due to infantile nystagmus might compare to those of experimental visual deprivation on refraction in a childhood series. METHODS: This was a retrospective analysis of data from the Danish Register for Blind and Weaksighted...... Children with infantile nystagmus recorded as prime diagnosis. We perused 90 records of children now aged 10-17 years, some of whom eventually exceeded the register borderline of 0.3 as best-corrected visual acuity. Spherical equivalent refraction was the primary outcome parameter, but visual acuity...

  2. Recurrent angioedema associated with hypogonadism or anti-androgen therapy.

    Science.gov (United States)

    Pichler, W J; Lehner, R; Späth, P J

    1989-10-01

    Two male patients with hypogonadism and four female patients who received an anti-androgen as contraceptive (cyproteronacetate) and who had recurrent angioedema are described. In one male patient, augmentation of the plasma androgen level resulted in disappearance of symptoms. In the four female patients, recurrent angioedema and urticaria developed after initiation of the anti-androgen treatment. Cessation of cyproteronacetate and a change to another contraceptive resulted in complete resolution of the previously frequent angioedematous attacks. The women are still symptom free after more than 60 patient's months. These cases suggest that an androgen deficit due to either hypogonadism or to anti-androgen treatment may be another cause of angioedema. One of the two male patients was untreated and presented with 40% normal value of C1-INH. Androgen therapy normalized C1-INH concentration in this male patient. Functional C1-INH in the same patient, studied before and after the beginning of androgen therapy, clearly increased when assessed by inhibition of amidolytic activity of C1-esterase. The other male patient with hypogonadism had already been under androgen treatment for 4 years and had C1-INH levels in the normal range. In the female patients, complement profiles were normal before and after cessation of anti-androgen contraception; however, the C1-INH plasma levels were higher after cessation of anti-androgen anticonception. These results indicate an effect of androgen deficit on the level of C1-INH in circulating plasma but do not prove a role of C1-INH in angioedema associated with diminished androgen plasma levels.

  3. Prostate cancer: molecular biology of early progression to androgen independence.

    Science.gov (United States)

    Sadar, M D; Hussain, M; Bruchovsky, N

    1999-12-01

    To improve the therapy for prostate cancer, it will be necessary to address the problems of progression to androgen independence and the process of metastatic spread of tumour. The complexity of the latter condition is likely to mitigate against the immediate development of relevant therapeutic approaches. However, the basis of androgen independence appears to be a problem of simpler dimensions and more amenable to treatment with current therapeutic technology. Since early tumour progression can be detected by an incomplete prostate-specific antigen (PSA) response to androgen withdrawal therapy, a study of the molecular biology of PSA gene regulation may well provide insight into new methods for preventing or delaying this problem. Mounting evidence suggests that ligand-independent activation of the androgen receptor may be one underlying mechanism of androgen independence. In the absence of androgen, a compensatory increase in the activity of cAMP-dependent protein kinase (PKA) enhances the ability of the androgen receptor to bind to the response elements regulating PSA gene expression. The activation of the androgen receptor through up-regulation of the PKA signal transduction pathway involves the amino-terminus of the androgen receptor, the function of which may be altered either by modifications such as phosphorylation, or through interactions with co-regulators or other proteins. Of therapeutic interest is the fact that this effect can be counteracted experimentally by the anti-androgen, bicalutamide, and clinically by several other similar agents. We speculate that the inhibition of PKA-activated androgen receptor might also be accomplished by decoy molecules that can bind to the relevant activated site on the amino-terminus or competitively interact with proteins recruited by the PKA pathway that are responsible for activating the receptor in the absence of androgen. Such molecules might include small mimetic substances or agents that can gain access to the

  4. Aberrant splicing of androgen receptor mRNA results in synthesis of a nonfunctional receptor protein in a patient with androgen insensitivity

    NARCIS (Netherlands)

    Ris-Stalpers, C.; Kuiper, G. G.; Faber, P. W.; Schweikert, H. U.; van Rooij, H. C.; Zegers, N. D.; Hodgins, M. B.; Degenhart, H. J.; Trapman, J.; Brinkmann, A. O.

    1990-01-01

    Androgen insensitivity is a disorder in which the correct androgen response in an androgen target cell is impaired. The clinical symptoms of this X chromosome-linked syndrome are presumed to be caused by mutations in the androgen receptor gene. We report a G----T mutation in the splice donor site of

  5. Bladder Management in Children: Intermittent Catheterization Education.

    Science.gov (United States)

    Fortuna, Suzanne Marie; Korcal, Layna; Thomas, Ginger

    2018-03-01

    Clean intermittent catheterization (IC) of the bladder is one example of advanced medical care required by students with special health care needs. The success of a child's intermittent catheterization program in a community setting such as a school is dependent on an educated team. This article discusses indications and problems that arise with IC bladder management in the pediatric population. The article also provides information about current best practice for IC management to assist school nurses in the optimization of bladder health.

  6. Pathological changes in anabolic androgenic steroid users.

    Science.gov (United States)

    Lusetti, Monia; Licata, Manuela; Silingardi, Enrico; Reggiani Bonetti, Luca; Palmiere, Cristian

    2015-07-01

    Several classes of recreational and prescription drugs have additional effects on the heart and vasculature, which may significantly contribute to morbidity and mortality in chronic users. The study presented herein focuses on pathological changes involving the heart possibly due to anabolic androgenic steroid use. The role these hormones may play in their occurrence of sudden cardiac death is also investigated. 98 medico-legal cases including 6 anabolic androgenic steroid users were retrospectively reviewed. Autopsies, histology, immunohistochemistry, biochemistry and toxicology were performed in all cases. Pathological changes consisted of various degrees of interstitial and perivascular fibrosis as well as fibroadipous metaplasia and perineural fibrosis within the myocardium of the left ventricle. Within the limits of the small number of investigated cases, our results appear to confirm former observations on this topic and suggest anabolic androgenic steroid's potential causative role in the pathogenesis of sudden cardiac deaths in chronic users. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  7. Androgen therapy in women, beyond libido.

    Science.gov (United States)

    Davis, S R

    2013-08-01

    The aim of this review was to summarize the literature regarding the potential role of testosterone therapy for women. The author conducted a search of the literature using Medline (Ovid, 1946-present) and PubMed (1966-2013) for English-language studies that included the following search terms: 'testosterone' or 'androgen' combined with 'women', 'therapy' or 'treatment'. Randomized, placebo-controlled trials have consistently shown that transdermal testosterone therapy improves sexual desire, arousal, orgasm frequency and satisfaction in premenopausal and postmenopausal women presenting with sexual desire/arousal problems. No adverse metabolic effects have been observed in these studies. In postmenopausal women, testosterone therapy has also been associated with favorable effects on body composition, bone, cardiovascular function and cognitive performance. Although androgens have many varied roles, the focus of testosterone therapy for women has been on improving sexual desire. Not only do testosterone effects on sexuality extend beyond libido, but testosterone has other key physiological actions. Issues that urgently need to be addressed include approval of a testosterone formulation that delivers a female dose such that physicians refrain from prescribing compounded testosterone or modifying doses of testosterone formulated for men and regulation of prescription of compounded androgens for women.

  8. Modulators of androgen and estrogen receptor activity.

    Science.gov (United States)

    Clarke, Bart L; Khosla, Sundeep

    2010-01-01

    This review focuses on significant recent findings regarding modulators of androgen and estrogen receptor activity. Selective androgen receptor modulators (SARMs) interact with androgen receptors (ARs), and selective estrogen receptor modulators (SERMs) interact with estrogen receptors (ERs), with variable tissue selectivity. SERMs, which interact with both ERб and ERв in a tissue-specific manner to produce diverse outcomes in multiple tissues, continue to generate significant interest for clinical application. Development of SARMs for clinical application has been slower to date because of potential adverse effects, but these diverse compounds continue to be investigated for use in disorders in which modulation of the AR is important. SARMs have been investigated mostly at the basic and preclinical level to date, with few human clinical trials published. These compounds have been evaluated mostly for application in different stages of prostate cancer to date, but they hold promise for multiple other applications. Publication of the large STAR and RUTH clinical trials demonstrated that the SERMs tamoxifen and raloxifene have interesting similarities and differences in tissues that contain ERs. Lasofoxifene, bazedoxifene, and arzoxifene are newer SERMs that have been demonstrated in clinical trials to more potently increase bone mineral density and lower serum cholesterol values than tamoxifen or raloxifene. Both SARMs and SERMs hold great promise for therapeutic use in multiple disorders in which tissue-specific effects are mediated by their respective receptors.

  9. The Role of (BETA)-Catenin in Androgen Receptor Signaling

    National Research Council Canada - National Science Library

    Bhowmick, Neil A

    2006-01-01

    .... Our preliminary data seem indicate stromally derived paracrine Wnt family members activate theepithelial frizzled receptor to enable prostate epithelial survival in an androgen deficient environment...

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Eunpi [University of Washington School of Medicine, Seattle, Washington (United States); Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Mostaghel, Elahe A. [Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Russell, Kenneth J.; Liao, Jay J.; Konodi, Mark A. [University of Washington School of Medicine, Seattle, Washington (United States); Kurland, Brenda F. [University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Marck, Brett T. [Veterans Affairs Puget Sound Health Care System, Seattle, Washington (United States); Matsumoto, Alvin M. [University of Washington School of Medicine, Seattle, Washington (United States); Veterans Affairs Puget Sound Health Care System, Seattle, Washington (United States); Dalkin, Bruce L. [University of Washington School of Medicine, Seattle, Washington (United States); Montgomery, R. Bruce, E-mail: rbmontgo@uw.edu [University of Washington School of Medicine, Seattle, Washington (United States)

    2015-06-01

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

  12. Immediate error correction process following sleep deprivation.

    Science.gov (United States)

    Hsieh, Shulan; Cheng, I-Chen; Tsai, Ling-Ling

    2007-06-01

    Previous studies have suggested that one night of sleep deprivation decreases frontal lobe metabolic activity, particularly in the anterior cingulated cortex (ACC), resulting in decreased performance in various executive function tasks. This study thus attempted to address whether sleep deprivation impaired the executive function of error detection and error correction. Sixteen young healthy college students (seven women, nine men, with ages ranging from 18 to 23 years) participated in this study. Participants performed a modified letter flanker task and were instructed to make immediate error corrections on detecting performance errors. Event-related potentials (ERPs) during the flanker task were obtained using a within-subject, repeated-measure design. The error negativity or error-related negativity (Ne/ERN) and the error positivity (Pe) seen immediately after errors were analyzed. The results show that the amplitude of the Ne/ERN was reduced significantly following sleep deprivation. Reduction also occurred for error trials with subsequent correction, indicating that sleep deprivation influenced error correction ability. This study further demonstrated that the impairment in immediate error correction following sleep deprivation was confined to specific stimulus types, with both Ne/ERN and behavioral correction rates being reduced only for trials in which flanker stimuli were incongruent with the target stimulus, while the response to the target was compatible with that of the flanker stimuli following sleep deprivation. The results thus warrant future systematic investigation of the interaction between stimulus type and error correction following sleep deprivation.

  13. Exercise training for intermittent claudication.

    Science.gov (United States)

    McDermott, Mary M

    2017-11-01

    The objective of this study was to provide an overview of evidence regarding exercise therapies for patients with lower extremity peripheral artery disease (PAD). This manuscript summarizes the content of a lecture delivered as part of the 2016 Crawford Critical Issues Symposium. Multiple randomized clinical trials demonstrate that supervised treadmill exercise significantly improves treadmill walking performance in people with PAD and intermittent claudication symptoms. A meta-analysis of 25 randomized trials demonstrated a 180-meter increase in treadmill walking distance in response to supervised exercise interventions compared with a nonexercising control group. Supervised treadmill exercise has been inaccessible to many patients with PAD because of lack of medical insurance coverage. However, in 2017, the Centers for Medicare and Medicaid Services issued a decision memorandum to support health insurance coverage of 12 weeks of supervised treadmill exercise for patients with walking impairment due to PAD. Recent evidence also supports home-based walking exercise to improve walking performance in people with PAD. Effective home-exercise programs incorporate behavioral change interventions such as a remote coach, goal setting, and self-monitoring. Supervised treadmill exercise programs preferentially improve treadmill walking performance, whereas home-based walking exercise programs preferentially improve corridor walking, such as the 6-minute walk test. Clinical trial evidence also supports arm or leg ergometry exercise to improve walking endurance in people with PAD. Treadmill walking exercise appears superior to resistance training alone for improving walking endurance. Supervised treadmill exercise significantly improves treadmill walking performance in people with PAD by approximately 180 meters compared with no exercise. Recent evidence suggests that home-based exercise is also effective and preferentially improves over-ground walking performance, such as

  14. A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility.

    Science.gov (United States)

    Desai, Mahesh S; Seekatz, Anna M; Koropatkin, Nicole M; Kamada, Nobuhiko; Hickey, Christina A; Wolter, Mathis; Pudlo, Nicholas A; Kitamoto, Sho; Terrapon, Nicolas; Muller, Arnaud; Young, Vincent B; Henrissat, Bernard; Wilmes, Paul; Stappenbeck, Thaddeus S; Núñez, Gabriel; Martens, Eric C

    2016-11-17

    Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota, and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome, and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. The PPARγ ligand ciglitazone regulates androgen receptor activation differently in androgen-dependent versus androgen-independent human prostate cancer cells

    International Nuclear Information System (INIS)

    Moss, Patrice E.; Lyles, Besstina E.; Stewart, LaMonica V.

    2010-01-01

    The androgen receptor (AR) regulates growth and progression of androgen-dependent as well as androgen-independent prostate cancer cells. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have been reported to reduce AR activation in androgen-dependent LNCaP prostate cancer cells. To determine whether PPARγ ligands are equally effective at inhibiting AR activity in androgen-independent prostate cancer, we examined the effect of the PPARγ ligands ciglitazone and rosiglitazone on C4-2 cells, an androgen- independent derivative of the LNCaP cell line. Luciferase-based reporter assays and Western blot analysis demonstrated that PPARγ ligand reduced dihydrotestosterone (DHT)-induced increases in AR activity in LNCaP cells. However, in C4-2 cells, these compounds increased DHT-induced AR driven luciferase activity. In addition, ciglitazone did not significantly alter DHT-mediated increases in prostate specific antigen (PSA) protein or mRNA levels within C4-2 cells. siRNA-based experiments demonstrated that the ciglitazone-induced regulation of AR activity observed in C4-2 cells was dependent on the presence of PPARγ. Furthermore, overexpression of the AR corepressor cyclin D1 inhibited the ability of ciglitazone to induce AR luciferase activity in C4-2 cells. Thus, our data suggest that both PPARγ and cyclin D1 levels influence the ability of ciglitazone to differentially regulate AR signaling in androgen-independent C4-2 prostate cancer cells.

  16. Sleep deprivation affects reactivity to positive but not negative stimuli.

    Science.gov (United States)

    Pilcher, June J; Callan, Christina; Posey, J Laura

    2015-12-01

    The current study examined the effects of partial and total sleep deprivation on emotional reactivity. Twenty-eight partially sleep-deprived participants and 31 totally sleep-deprived participants rated their valence and arousal responses to positive and negative pictures across four testing sessions during the day following partial sleep deprivation or during the night under total sleep deprivation. The results suggest that valence and arousal ratings decreased under both sleep deprivation conditions. In addition, partial and total sleep deprivation had a greater negative effect on positive events than negative events. These results suggest that sleep-deprived persons are more likely to respond less to positive events than negative events. One explanation for the current findings is that negative events could elicit more attentive behavior and thus stable responding under sleep deprivation conditions. As such, sleep deprivation could impact reactivity to emotional stimuli through automated attentional and self-regulatory processes. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Sleep deprivation and neurobehavioral functioning in children.

    Science.gov (United States)

    Maski, Kiran P; Kothare, Sanjeev V

    2013-08-01

    Sleep deprivation can result in significant impairments in daytime neurobehavioral functioning in children. Neural substrates impacted by sleep deprivation include the prefrontal cortex, basal ganglia and amygdala and result in difficulties with executive functioning, reward anticipation and emotional reactivity respectively. In everyday life, such difficulties contribute to academic struggles, challenging behaviors and public health concerns of substance abuse and suicidality. In this article, we aim to review 1) core neural structures impacted by sleep deprivation; 2) neurobehavioral problems associated with sleep deprivation; 3) specific mechanisms that may explain the relationship between sleep disturbances and neurobehavioral dysfunction; and 4) sleep problems reported in common neurodevelopmental disorders including attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorders (ASDs). Published by Elsevier B.V.

  18. Court-authorised deprivation of liberty.

    Science.gov (United States)

    Griffith, Richard

    2015-01-01

    The United Kingdom Supreme Court judgment in Cheshire West and Chester Council v P in 2014 introduced a more inclusive 'acid test' for determining the objective element of a deprivation of liberty in cases concerning people who lack decision-making capacity. The case made clear that adults and young people who lack capacity could be deprived of their liberty in care settings other than hospitals and care homes, including the person's own home. A deprivation of liberty that occurs in a setting other than a hospital or care home must be authorised by a Court. This article explains the revised process for applying for Court authorisation of a deprivation of liberty where it occurs in supported living, Shared Lives placements or the incapable person's own home.

  19. Relative deprivation and disordered gambling in youths.

    Science.gov (United States)

    Elgar, Frank J; Canale, Natale; Wohl, Michael J A; Lenzi, Michela; Vieno, Alessio

    2018-03-07

    Previous research has found that area-level income inequality and individual-level relative deprivation both contribute to disordered gambling in adults. However, the socioeconomic factors that contribute to disordered gambling in youths and protective factors in their social environment have not been fully explored. This study examined the association between relative deprivation and youth disordered gambling and the potential moderating role of social support in this association. We used data on family material assets and self-reported symptoms of disordered gambling symptoms in 19 321 participants of the 2013/2014 Italian Health Behaviour in School-aged Children study. Relative deprivation was measured using the Yitzhaki index and classmates as a social reference group. Its association with disordered gambling was tested using multilevel negative binomial regression analyses. We also tested moderated effects of relative deprivation on disordered gambling by four sources of social support: families, peers, teachers and classmates. Relative deprivation related to a fourfold increase in the rate of disordered gambling symptoms (incidence rate ratio=4.18) after differences in absolute family wealth and other variables were statistically controlled. Symptoms were also more prevalent in males, first-generation immigrants and less supported youth. Peer support moderated the association between relative deprivation and symptoms, suggesting that high deprivation and low peer support have interactive links to disordered gambling. Relative deprivation among classmates relate to youth symptoms of disordered gambling. Youth who live in economically unequal settings and perceive a lack of social support may be at greatest risk. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Sensory deprivation leading to late onset psychosis

    Directory of Open Access Journals (Sweden)

    Swapnajeet Sahoo

    2016-01-01

    Full Text Available Sensory deprivation is understood as diminution or absence of perceptual experiences to the usual external stimuli. Sensory deprivation in elderly is reported to be associated with depression, anxiety, psychosis, dementia, etc. In this report, we present the case of an 84-year- elderly man who developed auditory hallucination and after 1 year of onset of hearing difficulties. He was managed with quetiapine, with which he showed significant improvement.

  1. Sleep deprivation increases formation of false memory

    OpenAIRE

    Lo, June C.; Chong, Pearlynne L. H.; Ganesan, Shankari; Leong, Ruth L. F.; Chee, Michael W. L.

    2016-01-01

    Summary Retrieving false information can have serious consequences. Sleep is important for memory, but voluntary sleep curtailment is becoming more rampant. Here, the misinformation paradigm was used to investigate false memory formation after 1 night of total sleep deprivation in healthy young adults (N?=?58, mean age???SD?=?22.10???1.60?years; 29 males), and 7 nights of partial sleep deprivation (5?h sleep opportunity) in these young adults and healthy adolescents (N?=?54, mean age???SD?=?1...

  2. Intrahousehold allocation of resources and household deprivation

    OpenAIRE

    Barcena-Martin, Elena

    2017-01-01

    This paper analyzes to what extent household financial regime, in terms of level of income pooling and decision-making responsibilities, is associated with different levels of household deprivation. We conclude that either pooling incomes and sharing decisions or not pooling income and female making decisions are associated with low deprivation levels. We identify household characteristics that are frequently associated with them such as higher household income levels, middle-aged households ...

  3. Comparative safety evaluation of selective androgen receptor modulators and anabolic androgenic steroids.

    Science.gov (United States)

    Choi, Seul Min; Lee, Byung-Mu

    2015-01-01

    Anabolic androgenic steroids (AASs) have been in use for decades for the treatment of short stature, severe burns, HIV wasting syndrome, osteoporosis, and anemia. However, their lack of selective effects on certain symptoms and unfavorable pharmacokinetic properties has limited their long-term usage in clinics. Selective androgen receptor modulators (SARMs) have some advantages over AASs; they are highly specific for androgen receptors, are orally available, and, most importantly, act as strong receptor agonists in skeletal muscle and bone, and as weak agonists or antagonists in androgen-responsive tissues such as the prostate and sebaceous glands. The exact molecular mechanism, however, has not been fully elucidated. This article includes a toxicological review of major AASs, and a comparative safety analysis of major AASs and SARMs in clinical trials to evaluate the therapeutic potential of SARMs. Based on the robust tissue selectivity of SARMs over AASs, they are worth considering as a promising therapeutic option for the treatment of various muscle-wasting diseases.

  4. Prostate Cancer Severity Associations with Neighborhood Deprivation

    Directory of Open Access Journals (Sweden)

    Charnita M. Zeigler-Johnson

    2011-01-01

    Full Text Available 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.

  5. Sleep deprivation and interference by emotional distracters.

    Science.gov (United States)

    Chuah, Lisa Y M; Dolcos, Florin; Chen, Annette K; Zheng, Hui; Parimal, Sarayu; Chee, Michael W L

    2010-10-01

    We determined if sleep deprivation would amplify the effect of negative emotional distracters on working memory. A crossover design involving 2 functional neuroimaging scans conducted at least one week apart. One scan followed a normal night of sleep and the other followed 24 h of sleep deprivation. Scanning order was counterbalanced across subjects. The study took place in a research laboratory. 24 young, healthy volunteers with no history of any sleep, psychiatric, or neurologic disorders. N/A. Study participants were scanned while performing a delayed-response working memory task. Two distracters were presented during the maintenance phase, and these differed in content: highly arousing, negative emotional scenes; low-arousing, neutral scenes; and digitally scrambled versions of the pictures. Irrespective of whether volunteers were sleep deprived, negative emotional (relative to neutral) distracters elicited greater maintenance-related activity in the amygdala, ventrolateral prefrontal cortex, and fusiform gyri, while concurrently depressing activity in cognitive control regions. Individuals who maintained or increased distracter-related amygdala activation after sleep deprivation showed increased working memory disruptions by negative emotional distracters. These individuals also showed reduced functional connectivity between the amygdala and the ventromedial and dorsolateral prefrontal cortices, regions postulated to mediate cognitive control against emotional distraction. Increased distraction by emotional stimuli following sleep deprivation is accompanied by increases in amygdala activation and reduced functional connectivity between the amygdala and prefrontal cognitive control regions. These findings shed light on the neural basis for interindividual variation in how negative emotional stimuli might distract sleep deprived persons.

  6. Additive effects of dietary glycotoxins and androgen excess on the ...

    African Journals Online (AJOL)

    AGE immunoreactivity was higher on the renal tubules of the androgenized animals fed with HA diet, when compared with the animals fed with LA diet, but did not significantly differ among the two groups. Conclusions: The above mentioned data suggest that dietary glycotoxins, in combination with increased androgen ...

  7. Anabolic-androgenic steroids for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2006-01-01

    Alcohol is one of the most common causes of liver disease in the Western World. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease.......Alcohol is one of the most common causes of liver disease in the Western World. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease....

  8. ENVIRONMENTAL ANDROGENS AND ANTIANDROGENS: AN EXPANDING CHEMICAL UNIVERSE

    Science.gov (United States)

    Within the last ten years, awareness has grown about environmental chemicals that display antiandrogenic or androgenic activity. While studies in the early 1990s focused on pesticides that acted as androgen receptor (AR) antagonists, it soon became evident that this was not the ...

  9. New selective estrogen and androgen receptor modulators.

    Science.gov (United States)

    Clarke, Bart L; Khosla, Sundeep

    2009-07-01

    The present review focuses on the most significant recent findings regarding selective estrogen receptor modulators (SERMs) and selective androgen receptor modulators (SARMs). SERMs, which interact with estrogen receptor-alpha and estrogen receptor-beta in multiple tissues, continue to generate clinical interest in potential applications in as many disorders as the tissues in which the two known receptors are found. SARMs have been demonstrated to have fewer clinical applications to date, but continue to be investigated for use in multiple disorders in which androgen receptor modulation is likely to be important. Both types of compounds hold great promise for therapeutic use in multiple hormonal disorders involving tissue-specific effects mediated by estrogen or androgen receptors. Although SERMs have been available for clinical use for 50 years, recent investigation has focused on large randomized clinical trials for newer indications of older agents or smaller clinical trials of newer agents with improved clinical activity and reduced side effects in specific tissues. In particular, the large, prospective, randomized, controlled, multiyear Study of Tamoxifen and Raloxifene and Raloxifene Use in the Heart clinical trials have recently shown interesting similarities and differences between tamoxifen and raloxifene in estrogen-responsive tissues. Lasofoxifene and arzoxifene are two newer SERMs that have recently been demonstrated to improve bone mineral density and lower serum cholesterol values compared with older SERMs in smaller clinical trials. SARMs are a newer category of drug still being investigated mostly at the basic and preclinical level, with fewer clinical trials available for review. SARMs are currently being investigated mostly for use in prostate cancer at different stages but hold promise for multiple other applications. Recent clinical trials indicate that SERMs are useful in treatment of disorders of bone and mineral metabolism and breast cancer

  10. The Yo-Yo intermittent recovery test

    DEFF Research Database (Denmark)

    Bangsbo, Jens; Iaia, F. Marcello; Krustrup, Peter

    2008-01-01

    The two Yo-Yo intermittent recovery (IR) tests evaluate an individual's ability to repeatedly perform intense exercise. The Yo-Yo IR level 1 (Yo-Yo IR1) test focuses on the capacity to carry out intermittent exercise leading to a maximal activation of the aerobic system, whereas Yo-Yo IR level 2...... (Yo-Yo IR2) determines an individual's ability to recover from repeated exercise with a high contribution from the anaerobic system. Evaluations of elite athletes in various sports involving intermittent exercise showed that the higher the level of competition the better an athlete performs in the Yo......-Yo IR tests. Performance in the Yo-Yo IR tests for young athletes increases with rising age. The Yo-Yo IR tests have shown to be a more sensitive measure of changes in performance than maximum oxygen uptake. The Yo-Yo IR tests provide a simple and valid way to obtain important information...

  11. Assessing relative volatility/intermittency/energy dissipation

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole E.; Pakkanen, Mikko S.; Schmiegel, Jürgen

    2014-01-01

    process in particular. This estimation method is motivated by the assessment of relative energy dissipation in empirical data of turbulence, but it is also applicable in other areas. We develop a probabilistic asymptotic theory for realised relative power variations of Brownian semistationary processes......, and introduce inference methods based on the theory. We also discuss how to extend the asymptotic theory to other classes of processes exhibiting stochastic volatility/intermittency. As an empirical application, we study relative energy dissipation in data of atmospheric turbulence.......We introduce the notion of relative volatility/intermittency and demonstrate how relative volatility statistics can be used to estimate consistently the temporal variation of volatility/intermittency when the data of interest are generated by a non-semimartingale, or a Brownian semistationary...

  12. Forces and energetics of intermittent swimming

    Science.gov (United States)

    Floryan, Daniel; Van Buren, Tyler; Smits, Alexander J.

    2017-08-01

    Experiments are reported on intermittent swimming motions. Water tunnel experiments on a nominally two-dimensional pitching foil show that the mean thrust and power scale linearly with the duty cycle, from a value of 0.2 all the way up to continuous motions, indicating that individual bursts of activity in intermittent motions are independent of each other. This conclusion is corroborated by particle image velocimetry (PIV) flow visualizations, which show that the main vortical structures in the wake do not change with duty cycle. The experimental data also demonstrate that intermittent motions are generally energetically advantageous over continuous motions. When metabolic energy losses are taken into account, this conclusion is maintained for metabolic power fractions less than 1.

  13. Masking effect of anti-androgens on androgenic activity in European river sediment unveiled by effect-directed analysis

    NARCIS (Netherlands)

    Weiss, J.M.; Hamers, T.; Thomas, K.; van der Linden, S.C.; Leonards, P.E.G.; Lamoree, M.H.

    2009-01-01

    This study shows that the androgen receptor agonistic potency is clearly concealed by the effects of androgen receptor antagonists in a total sediment extract, demonstrating that toxicity screening of total extracts is not enough to evaluate the full in vitro endocrine disrupting potential of a

  14. RAINBOW TROUT ANDROGEN RECEPTOR ALPHA AND THE HUMAN ANDROGEN RECEPTOR: COMPARISONS IN THE COS WHOLE CELL BINDING ASSAY

    Science.gov (United States)

    Rainbow Trout Androgen Receptor Alpha And Human Androgen Receptor: Comparisons in the COS Whole Cell Binding Assay Mary C. Cardon, L. Earl Gray, Jr. and Vickie S. WilsonU.S. Environmental Protection Agency, ORD, NHEERL, Reproductive Toxicology Division, Research Triangle...

  15. Functional analysis of a novel androgen receptor mutation, Q902K, in an individual with partial androgen insensitivity.

    NARCIS (Netherlands)

    A. Umar (Arzu); C.A. Berrevoets (Cor); N.M. Van (Mai); M. van Leeuwen (Marije); M.M.P.J. Verbiest (Michael); W.J. Kleijer (Wim); D. Dooijes (Dennis); J.A. Grootegoed (Anton); S.L.S. Drop (Stenvert); A.O. Brinkmann (Albert)

    2005-01-01

    textabstractAndrogen insensitivity syndrome (AIS) is caused by defects in the androgen receptor (AR) that render the AR partially or completely inactive. As a result, embryonic sex differentiation is impaired. Here, we describe a novel mutation in the AR found in a patient with

  16. The long-term outcome of boys with partial androgen insensitivity syndrome and a mutation in the androgen receptor gene

    NARCIS (Netherlands)

    Lucas-Herald, A.; S. Bertelloni (Silvano); A. Juul (Anders); J. Bryce (Jillian); Jiang, J.; M. Rodie (Martina); R. Sinnott (Richard); Boroujerdi, M.; Lindhardt Johansen, M.; O. Hiort (Olaf); P-M. Holterhus (Paul-Martin); M.L. Cools (Martine); Guaragna-Filho, G.; Guerra-Junior, G.; N. Weintrob (Naomi); S.E. Hannema (Sabine); S.L.S. Drop (Stenvert); T. Guran (Tulay); F. Darendeliler (Feyza); A. Nordenström (Anna); I.A. Hughes (Ieuan A.); Acerini, C.; Tadokoro-Cuccaro, R.; S.F. Ahmed (Faisal)

    2016-01-01

    textabstractBackground: In boys with suspected partial androgen insensitivity syndrome (PAIS), systematic evidence that supports the long-term prognostic value of identifying a mutation in the androgen receptor gene (AR) is lacking. Objective: To assess the clinical characteristics and long-term

  17. Unsteady propulsion by an intermittent swimming gait

    Science.gov (United States)

    Akoz, Emre; Moored, Keith W.

    2018-01-01

    Inviscid computational results are presented on a self-propelled swimmer modeled as a virtual body combined with a two-dimensional hydrofoil pitching intermittently about its leading edge. Lighthill (1971) originally proposed that this burst-and-coast behavior can save fish energy during swimming by taking advantage of the viscous Bone-Lighthill boundary layer thinning mechanism. Here, an additional inviscid Garrick mechanism is discovered that allows swimmers to control the ratio of their added mass thrust-producing forces to their circulatory drag-inducing forces by decreasing their duty cycle, DC, of locomotion. This mechanism can save intermittent swimmers as much as 60% of the energy it takes to swim continuously at the same speed. The inviscid energy savings are shown to increase with increasing amplitude of motion, increase with decreasing Lighthill number, Li, and switch to an energetic cost above continuous swimming for sufficiently low DC. Intermittent swimmers are observed to shed four vortices per cycle that form into groups that are self-similar with the DC. In addition, previous thrust and power scaling laws of continuous self-propelled swimming are further generalized to include intermittent swimming. The key is that by averaging the thrust and power coefficients over only the bursting period then the intermittent problem can be transformed into a continuous one. Furthermore, the intermittent thrust and power scaling relations are extended to predict the mean speed and cost of transport of swimmers. By tuning a few coefficients with a handful of simulations these self-propelled relations can become predictive. In the current study, the mean speed and cost of transport are predicted to within 3% and 18% of their full-scale values by using these relations.

  18. The Yo-Yo intermittent recovery test

    DEFF Research Database (Denmark)

    Bangsbo, Jens; Iaia, F. Marcello; Krustrup, Peter

    2008-01-01

    The two Yo-Yo intermittent recovery (IR) tests evaluate an individual's ability to repeatedly perform intense exercise. The Yo-Yo IR level 1 (Yo-Yo IR1) test focuses on the capacity to carry out intermittent exercise leading to a maximal activation of the aerobic system, whereas Yo-Yo IR level 2......-Yo IR tests. Performance in the Yo-Yo IR tests for young athletes increases with rising age. The Yo-Yo IR tests have shown to be a more sensitive measure of changes in performance than maximum oxygen uptake. The Yo-Yo IR tests provide a simple and valid way to obtain important information...

  19. Sprint cycling training improves intermittent run performance

    OpenAIRE

    Hardaway Chun-Kwan Chan; Weeraya Ka-Yan Ho; Patrick Shu-Hang Yung

    2018-01-01

    Background/Objective: The aim of this study was to examine the effect of sprint cycling training on the intermittent run performance, sprinting speed, and change of direction (COD) ability of recreational intermittent sports athletes. Methods: Sixteen participants participated in the study. The experimental group (EG, n = 8) received a total of 12 sessions of sprint cycling training in a 4-week period and the control group (CG, n = 8) received no training. Both EG and CG were instructed to...

  20. Androgens and estrogens in skeletal sexual dimorphism

    Science.gov (United States)

    Laurent, Michaël; Antonio, Leen; Sinnesael, Mieke; Dubois, Vanessa; Gielen, Evelien; Classens, Frank; Vanderschueren, Dirk

    2014-01-01

    Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conversion in bone tissue, for example, from testosterone (T) to estradiol (E2) by aromatase, or to dihydrotestosterone by 5α-reductase enzymes. Our understanding of the structural basis for gender differences in bone strength has advanced considerably over recent years due to increasing use of (high resolution) peripheral computed tomography. These microarchitectural insights form the basis to understand sex steroid influences on male peak bone mass and turnover in cortical vs trabecular bone. Recent studies using Cre/LoxP technology have further refined our mechanistic insights from global knockout mice into the direct contributions of sex steroids and their respective nuclear receptors in osteoblasts, osteoclasts, osteocytes, and other cells to male osteoporosis. At the same time, these studies have reinforced the notion that androgen and estrogen deficiency have both direct and pleiotropic effects via interaction with, for example, insulin-like growth factor 1, inflammation, oxidative stress, central nervous system control of bone metabolism, adaptation to mechanical loading, etc., This review will summarize recent advances on these issues in the field of sex steroid actions in male bone homeostasis. PMID:24385015

  1. Sleep deprivation impairs recognition of specific emotions

    Directory of Open Access Journals (Sweden)

    William D.S. Killgore

    2017-06-01

    Full Text Available Emotional processing is particularly sensitive to sleep deprivation, but research on the topic has been limited and prior studies have generally evaluated only a circumscribed subset of emotion categories. Here, we evaluated the effects of one night of sleep deprivation and a night of subsequent recovery sleep on the ability to identify the six most widely agreed upon basic emotion categories (happiness, surprise, fear, sadness, disgust, anger. Healthy adults (29 males; 25 females classified a series of 120 standard facial expressions that were computer morphed with their most highly confusable expression counterparts to create continua of expressions that differed in discriminability between emotion categories (e.g., combining 70% happiness+30% surprise; 90% surprise+10% fear. Accuracy at identifying the dominant emotion for each morph was assessed after a normal night of sleep, again following a night of total sleep deprivation, and finally after a night of recovery sleep. Sleep deprivation was associated with significantly reduced accuracy for identifying the expressions of happiness and sadness in the morphed faces. Gender differences in accuracy were not observed and none of the other emotions showed significant changes as a function of sleep loss. Accuracy returned to baseline after recovery sleep. Findings suggest that sleep deprivation adversely affects the recognition of subtle facial cues of happiness and sadness, the two emotions that are most relevant to highly evolved prosocial interpersonal interactions involving affiliation and empathy, while the recognition of other more primitive survival-oriented emotional face cues may be relatively robust against sleep loss.

  2. Effects of sleep deprivation on wound healing.

    Science.gov (United States)

    Mostaghimi, L; Obermeyer, W H; Ballamudi, B; Martinez-Gonzalez, D; Benca, R M

    2005-09-01

    Sleep deprivation is widely regarded as a stressor and has been shown to have significant effects on host defences. Severely sleep-deprived rats develop lesions on their paws and tails, suggesting possible deficits in the healing process. The purpose of this study was to assess the impact of rapid eye-movement (REM) sleep deprivation (RSD) on wound healing in a rat model. Male dark-hooded Long-Evans rats, 2-4 months old, were subjected to dorsal application of two sterile punch biopsies, each 3.5 mm in size. Biopsies were performed either immediately before or immediately after 5 days of sleep deprivation. Wound healing in REM sleep-deprived animals was compared with home cage control and yoked control animals. RSD did not produce differences in the rate of healing, regardless of the timing of the biopsy punch. RSD does not appear to have significant effects on wound healing and thus appears to act differently from other types of stressors on wound healing.

  3. Androgenic alopecia; the risk–benefit ratio of Finasteride

    Directory of Open Access Journals (Sweden)

    David L. Rowland

    2018-04-01

    Full Text Available Finasteride is currently approved and largely used as a therapeutic option for androgenetic alopecia. Apparently a safe drug and effective at the onset, several concerns appeared over time regarding the frequency and magnitude of finasteride adverse effects, which in some cases seem to be even irreversible. This paper presents administration of finasteride in androgenic alopecia from two distinct perspectives. On one hand, androgenic alopecia is a condition that affects especially the self-image and esteem, aspects that are subjective, namely changeable and thus relative. On the other hand, this condition presents a multifactorial etiology, androgens being only in part involved. In addition, androgens have their own physiological roles within the body, so that any androgenic suppression should be carefully advised. Yet, adverse effects induced by Finasteride are only in part documented and treatable. Finally, alternative therapeutic approaches (like topical finasteride become available, so that the oral administration of Finasteride for androgenic alopecia should be in our opinion reevaluated. As a conclusion, a very detailed and informed discussion should take place with such patients accepting to start a therapy with finasteride for androgenic alopecia.

  4. New insights into androgen treatment of erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Louis Gooren

    2006-01-01

    Full Text Available Erectile response in mammals is centrally and peripherally regulated by androgens. Severe hypogonadism in men usually results in loss of libido and potency which can be restored by androgen administration. The original insights into the mechanisms of action of androgens on sexual function indicated that androgens particularly exert effects on libido and that sleep-related erections were androgen-sensitive but erections in response to erotic stimuli were relatively androgen-independent. There are a number of recent developments which shed new light on testosterone treatment of erectile dysfunction in aging men. There is growing insight that testosterone has profound effects on tissues of the penis involved in the mechanism of erection and that testosterone deficiency impairs the anatomical and physiological/biochemical substrate of erectile capacity, reversible upon androgen treatment. Several studies have indicated that the administration of PDE-5-inhibitors is not always sufficient to restore erectile potency in men and that administration of testosterone improves the therapeutical response to PDE-5-inhibitors considerably. There is increasing insight not to view erectile dysfunction (ED as a single entity but as part of the aging process. Circulating levels of testosterone are closely related to manifestations of other etiological factors in ED, such as atherosclerotic disease and diabetes mellitus. The latter are correlated with lower-than-normal testosterone levels.

  5. Fractal structures and intermittency in QCD

    International Nuclear Information System (INIS)

    Gustafson, Goesta.

    1990-04-01

    New results are presented for fractal structures and intermittency in QCD parton showers. A geometrical interpretation of the anomalous dimension in QCD is given. It is shown that model predications for factorial moments in the PEP-PETRA energy range are increased. if the properties of directly produced pions are more carefully taken into account

  6. Intermittent mechanical and clinical intravalvar regurgitation aortic ...

    African Journals Online (AJOL)

    due to intravalvar occlusion caused by thrombosis and/or tissue ingrowth or to periprosthetic regurgitation. .... position). A. The tilting disc of the prosthetic aortic valve is in the normal closed position during diastole. B. The disc is 'stuck' in the open position during diastole. Intermittent AR in patients with aortic prosthetic ...

  7. Intermittent and global transitions in plasma turbulence

    International Nuclear Information System (INIS)

    Vlad, M.; Spineanu, F.; Itoh, K.; Itoh, S.-I.

    2003-07-01

    The dynamics of the transition processes in plasma turbulence described by the nonlinear Langevin equation (1) is studied. We show that intermittent or global transitions between metastable states can appear. The conditions for the generation of these transitions and their statistical characteristics are determined. (author)

  8. Acute intermittent porphyria presenting as progressive muscular ...

    African Journals Online (AJOL)

    Acute intermittent porphyria, the most common porphyria affecting the nervous system, typically presents with neurovisceral crises followed by a motor neuropathy. We describe a 23-year-old black South African man presenting with a progressive stuttering, lower motor neuron syndrome developing over months. He had not ...

  9. Walking training for intermittent claudication in diabetes

    NARCIS (Netherlands)

    Ubels, FL; Links, TP; Sluiter, WJ; Smit, AJ

    OBJECTIVE - Walking training (WT) is an established treatment for patients with intermittent claudication (IC). Abnormalities specific to diabetes, such as a relative preponderance of distal lesions and the contribution of microcirculatory disease, might well influence the results of WT. We compared

  10. Cooling tower modification for intermittent operation

    International Nuclear Information System (INIS)

    Midkiff, W.S.

    1975-03-01

    One of the cooling towers at Los Alamos Scientific Laboratory is being operated intermittently. The cooling tower has been modified to restrict air flow and to keep the tower from drying out. The modifications are relatively inexpensive, simple to operate, and have proved effective. (U.S.)

  11. Intermittent demand : Linking forecasting to inventory obsolescence

    NARCIS (Netherlands)

    Teunter, Ruud H.; Syntetos, Aris A.; Babai, M. Zied

    2011-01-01

    The standard method to forecast intermittent demand is that by Croston. This method is available in ERP-type solutions such as SAP and specialised forecasting software packages (e.g. Forecast Pro), and often applied in practice. It uses exponential smoothing to separately update the estimated demand

  12. Prevalence of intermittent preventive treatment with sulphadoxine ...

    African Journals Online (AJOL)

    Cite as: Orish VN, Onyeabor OS, Boampong JN , Afoakwah R, Nwaefuna E, Acquah S, et al. Prevalence of intermittent preventive treat- ment with sulphadoxine-pyrimethamine (IPTp-SP) use ..... by the increase of SP drug resistance in pregnant wom- en in Ghana since the adoption and implementation of. IPTp-SP policy35.

  13. Intermittent resistive faults in digital cmos circuits

    NARCIS (Netherlands)

    Kerkhoff, Hans G.; Ebrahimi, Hassan

    2015-01-01

    A major threat in extremely dependable high-end process node integrated systems in e.g. Avionics are no failures found (NFF). One category of NFFs is the intermittent resistive fault, often originating from bad (e.g. Via or TSV-based) interconnections. This paper will show the impact of these faults

  14. Androgenic Regulation of Male Sexual Behavior and Physiology in the Syrian Hamster (Mesocricetus Auratus)

    OpenAIRE

    Piekarski, David John

    2012-01-01

    The androgen testosterone (T) and its metabolite, dihydrotestosterone (DHT), are released from the gonads and act in the brain and periphery to control many male-typical traits, including male sexual behavior (MSB). The classical model of androgenic action asserts that T, or DHT binds to a single species of intracellular androgen receptor (AR), that acts as a transcription factor to induce transactivation of androgen-regulated genes. Accordingly, androgens may take hours or days to assert t...

  15. Blood androgen levels in male baboons throughout the year

    International Nuclear Information System (INIS)

    Taranov, A.G.; Goncharov, N.P.

    1986-01-01

    This paper describes a study of possible dependence of the androgen level in male baboons on the time of year. Plasma was obtained by centrifugation of the blood at 3000 rpm and the following androgens were determined by radioimmunoassay, using chromatographic separation of the steroids on columns with celite: testosterone, 5s-dihydrotestosterone, and dehydroepiandrosterone. Plasma steriod concentrations were calculated and the results were subjected to statistical analysis by Students test. Seasonal change in the concentration of steroids in the animals' blood plasma were discovered. The results of androgen assay throughout the year and determination of their mean annual concentrations are shown

  16. ANABOLIC ANDROGENIC STEROIDS AND ADVERSE EVENTS OF THEIR APPLICATION

    Directory of Open Access Journals (Sweden)

    Nina Đukanović

    2011-08-01

    Full Text Available Anabolic androgenic steroids are synthetic compounds originating from testosterone. Their main effects are the control of development and expression of male secondary sexual characteristics, which are known as androgenic effects, and encourage muscle growth or anabolic effects. Anabolic androgenic steroids are most commonly used illegal substances. Besides these physiological effects, which are achieved using therapeutic doses of these preparations, higher doses than recommended, especially over the longer term, may be associated with the emergence of numerous adverse events. Adverse events may be registered in almost all organs and organ systems, but usually include changes in the reproductive system, skin, liver and cardiovascular system.

  17. Androgenic anabolic steroids also impair right ventricular function.

    Science.gov (United States)

    Kasikcioglu, Erdem; Oflaz, Huseyin; Umman, Berrin; Bugra, Zehra

    2009-05-01

    Chronic anabolic steroid use suppresses left ventricular functions. However, there is no information regarding the chronic effects of anabolic steroids on right ventricular function which also plays a key role in global cardiac function. The main objective of the present study was to investigate the effects of androgenic anabolic steroids usage among athletes on remodeling the right part of the heart. Androgenic-anabolic steroids-using bodybuilders had smaller diastolic velocities of both ventricles than drug-free bodybuilders and sedentary counterparts. This study shows that androgenic anabolic steroids-using bodybuilders exhibited depressed diastolic functions of both ventricles.

  18. [Bone and Men's Health. Bone selective androgen receptor modulators].

    Science.gov (United States)

    Furuya, Kazuyuki

    2010-02-01

    Androgen, one of the sex steroid hormones shows various biological activities on the corresponding various tissues. Many efforts to produce novel drug materials maintaining a desired biological activity with an adequate tissue selectivity, which is so-called selective androgen receptor modulators (SARMs) , are being performed. As one of such efforts, studies on SARMs against bone tissues which possess a significant potential to stimulate a bone formation with reducing undesirable androgenic virilizing activities are in progress all over the world. This review focuses on the research and development activities of such SARMs and discuses their usefulness for the treatment of osteoporosis.

  19. 40 CFR 51.119 - Intermittent control systems.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 2 2010-07-01 2010-07-01 false Intermittent control systems. 51.119... Intermittent control systems. (a) The use of an intermittent control system (ICS) may be taken into account in... of any constant pollution control system which was in use before December 31, 1970, or the equivalent...

  20. Nursing diagnoses in women deprived of freedom

    Directory of Open Access Journals (Sweden)

    Izabelle de Freitas Ferreira

    2016-05-01

    Full Text Available Objective: to analyze the nursing diagnoses profile of women deprived of freedom, using the International Classification for Nursing® Practice version 1.0. Methods: a descriptive study, conducted with 186 women deprived of freedom. Nursing Diagnoses were extrapolated based on the clinical data of the participants, collected through a structured form and clinical reasoning. Results: there were 44 nursing diagnostic statements, among the most common, there were: infection risk (70.9%; fluid intake, decreased (61.2%; Sleep, impaired (60.7%; tobacco abuse, started (51.6%; health seeking behavior, committed (50.0%. Conclusion: the diagnoses are related to factors that compromise the biopsychosocial health. The nurse, health staff member in the prison setting, must recognize and assess the individual and collective needs of women deprived of freedom. The inference of nursing diagnoses, based on clinical reasoning, contributes to a humanized, empathic and special care.

  1. Neuroendocrine prostate cancer (NEPCa) increased the neighboring PCa chemo-resistance via altering the PTHrP/p38/Hsp27/androgen receptor (AR)/p21 signals

    Science.gov (United States)

    Cui, Yun; Sun, Yin; Hu, Shuai; Luo, Jie; Li, Lei; Li, Xin; Yeh, Shuyuan; Jin, Jie; Chang, Chawnshang

    2016-01-01

    Prostatic neuroendocrine cells (NE) are an integral part of prostate cancer (PCa) that are associated with PCa progression. As the current androgen-deprivation therapy (ADT) with anti-androgens may promote the neuroendocrine PCa (NEPCa) development, and few therapies can effectively suppress NEPCa, understanding the impact of NEPCa on PCa progression may help us to develop better therapies to battle PCa. Here we found NEPCa cells could increase the docetaxel-resistance of their neighboring PCa cells. Mechanism dissection revealed that through secretion of PTHrP, NEPCa cells could alter the p38/MAPK/Hsp27 signals in their neighboring PCa cells that resulted in increased androgen receptor (AR) activity via promoting AR nuclear translocation. The consequences of increased AR function might then increase docetaxel-resistance via increasing p21 expression. In vivo xenograft mice experiments also confirmed NEPCa could increase the docetaxel-resistance of neighboring PCa, and targeting this newly identified PTHrP/p38/Hsp27/AR/p21 signaling pathway with either p38 inhibitor (SB203580) or sh-PTHrP may result in improving/restoring the docetaxel sensitivity to better suppress PCa. PMID:27375022

  2. Differential regulation of metabolic pathways by androgen receptor (AR) and its constitutively active splice variant, AR-V7, in prostate cancer cells.

    Science.gov (United States)

    Shafi, Ayesha A; Putluri, Vasanta; Arnold, James M; Tsouko, Efrosini; Maity, Suman; Roberts, Justin M; Coarfa, Cristian; Frigo, Daniel E; Putluri, Nagireddy; Sreekumar, Arun; Weigel, Nancy L

    2015-10-13

    Metastatic prostate cancer (PCa) is primarily an androgen-dependent disease, which is treated with androgen deprivation therapy (ADT). Tumors usually develop resistance (castration-resistant PCa [CRPC]), but remain androgen receptor (AR) dependent. Numerous mechanisms for AR-dependent resistance have been identified including expression of constitutively active AR splice variants lacking the hormone-binding domain. Recent clinical studies show that expression of the best-characterized AR variant, AR-V7, correlates with resistance to ADT and poor outcome. Whether AR-V7 is simply a constitutively active substitute for AR or has novel gene targets that cause unique downstream changes is unresolved. Several studies have shown that AR activation alters cell metabolism. Using LNCaP cells with inducible expression of AR-V7 as a model system, we found that AR-V7 stimulated growth, migration, and glycolysis measured by ECAR (extracellular acidification rate) similar to AR. However, further analyses using metabolomics and metabolic flux assays revealed several differences. Whereas AR increased citrate levels, AR-V7 reduced citrate mirroring metabolic shifts observed in CRPC patients. Flux analyses indicate that the low citrate is a result of enhanced utilization rather than a failure to synthesize citrate. Moreover, flux assays suggested that compared to AR, AR-V7 exhibits increased dependence on glutaminolysis and reductive carboxylation to produce some of the TCA (tricarboxylic acid cycle) metabolites. These findings suggest that these unique actions represent potential therapeutic targets.

  3. Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs.

    Directory of Open Access Journals (Sweden)

    Kathy Bailey

    Full Text Available Testosterone (T and related androgens are performance enhancing drugs (PEDs abused by some athletes to gain competitive advantage. To monitor unauthorized androgen abuse, doping control programs use mass spectrometry (MS to detect androgens, synthetic anabolic-androgenic steroids (AASs and their metabolites in an athlete's urine. AASs of unknown composition will not be detected by these procedures. Since AASs achieve their anabolic effects by activating the Androgen Receptor (AR, cell-based bioassays that measure the effect of a urine sample on AR activity are under investigation as complementary, pan-androgen detection methods. We evaluated an AR BioAssay as a monitor for androgen activity in urine pre-treated with glucuronidase, which releases T from the inactive T-glucuronide that predominates in urine. AR BioAssay activity levels were expressed as 'T-equivalent' concentrations by comparison to a T dose response curve. The T-equivalent concentrations of androgens in the urine of hypogonadal participants supplemented with T (in whom all androgenic activity should arise from T were quantitatively identical to the T measurements conducted by MS at the UCLA Olympic Analytical Laboratory (0.96 ± 0.22. All 17 AASs studied were active in the AR BioAssay; other steroids were inactive. 12 metabolites of 10 commonly abused AASs, which are used for MS monitoring of AAS doping because of their prolonged presence in urine, had reduced or no AR BioAssay activity. Thus, the AR BioAssay can accurately and inexpensively monitor T, but its ability to monitor urinary AASs will be limited to a period immediately following doping in which the active AASs remain intact.

  4. Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs.

    Science.gov (United States)

    Bailey, Kathy; Yazdi, Tahmineh; Masharani, Umesh; Tyrrell, Blake; Butch, Anthony; Schaufele, Fred

    2016-01-01

    Testosterone (T) and related androgens are performance enhancing drugs (PEDs) abused by some athletes to gain competitive advantage. To monitor unauthorized androgen abuse, doping control programs use mass spectrometry (MS) to detect androgens, synthetic anabolic-androgenic steroids (AASs) and their metabolites in an athlete's urine. AASs of unknown composition will not be detected by these procedures. Since AASs achieve their anabolic effects by activating the Androgen Receptor (AR), cell-based bioassays that measure the effect of a urine sample on AR activity are under investigation as complementary, pan-androgen detection methods. We evaluated an AR BioAssay as a monitor for androgen activity in urine pre-treated with glucuronidase, which releases T from the inactive T-glucuronide that predominates in urine. AR BioAssay activity levels were expressed as 'T-equivalent' concentrations by comparison to a T dose response curve. The T-equivalent concentrations of androgens in the urine of hypogonadal participants supplemented with T (in whom all androgenic activity should arise from T) were quantitatively identical to the T measurements conducted by MS at the UCLA Olympic Analytical Laboratory (0.96 ± 0.22). All 17 AASs studied were active in the AR BioAssay; other steroids were inactive. 12 metabolites of 10 commonly abused AASs, which are used for MS monitoring of AAS doping because of their prolonged presence in urine, had reduced or no AR BioAssay activity. Thus, the AR BioAssay can accurately and inexpensively monitor T, but its ability to monitor urinary AASs will be limited to a period immediately following doping in which the active AASs remain intact.

  5. Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs

    Science.gov (United States)

    Bailey, Kathy; Yazdi, Tahmineh; Masharani, Umesh; Tyrrell, Blake; Butch, Anthony; Schaufele, Fred

    2016-01-01

    Testosterone (T) and related androgens are performance enhancing drugs (PEDs) abused by some athletes to gain competitive advantage. To monitor unauthorized androgen abuse, doping control programs use mass spectrometry (MS) to detect androgens, synthetic anabolic-androgenic steroids (AASs) and their metabolites in an athlete’s urine. AASs of unknown composition will not be detected by these procedures. Since AASs achieve their anabolic effects by activating the Androgen Receptor (AR), cell-based bioassays that measure the effect of a urine sample on AR activity are under investigation as complementary, pan-androgen detection methods. We evaluated an AR BioAssay as a monitor for androgen activity in urine pre-treated with glucuronidase, which releases T from the inactive T-glucuronide that predominates in urine. AR BioAssay activity levels were expressed as ‘T-equivalent’ concentrations by comparison to a T dose response curve. The T-equivalent concentrations of androgens in the urine of hypogonadal participants supplemented with T (in whom all androgenic activity should arise from T) were quantitatively identical to the T measurements conducted by MS at the UCLA Olympic Analytical Laboratory (0.96 ± 0.22). All 17 AASs studied were active in the AR BioAssay; other steroids were inactive. 12 metabolites of 10 commonly abused AASs, which are used for MS monitoring of AAS doping because of their prolonged presence in urine, had reduced or no AR BioAssay activity. Thus, the AR BioAssay can accurately and inexpensively monitor T, but its ability to monitor urinary AASs will be limited to a period immediately following doping in which the active AASs remain intact. PMID:26998755

  6. Deprivation of Dignity in Nursing Home Residents

    DEFF Research Database (Denmark)

    Høy, Bente

    2016-01-01

    deepened knowledge in how to maintain and promote dignity in nursing home residents. The purpose of this paper is to present results concerning the question: How is nursing home residents’ dignity maintained or deprived from the perspective of close family caregivers? In this presentation we only focus...... on deprivation of dignity. Methodology: The overall design of this study is modified clinical application research. The study took place at six different nursing home residences in Sweden, Denmark and Norway. Data collection methods were individual research interviews. All together the sample consisted of 28...

  7. [Is the socioeconomic deprivation EPICES score useful in obstetrics?].

    Science.gov (United States)

    Convers, M; Langeron, A; Sass, C; Moulin, J-J; Augier, A; Varlet, M-N; Seffert, P; Chêne, G

    2012-04-01

    To describe a validated and multifactorial deprivation score to study the relationship between socioeconomic deprivation and perinatal risks. The index of deprivation EPICES (Evaluation of Precarity and Inequalities in Health Examination Centers) was used to characterize the deprivation status of 234 women in post-partum in comparison with perinatal morbidity. The cutoff value of 30.7 was the threshold to define deprivation. Two hundred and eight patients were included in this retrospective study from whom 48 (23%) had a score of deprivation higher than 30.7. Maternofetal morbidity was more severe in deprived patients. The current results show that the EPICES score could be a useful obstetrical tool for the identification of deprived women during pregnancy. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  8. Deprivation of Liberty Safeguards: ethical and clinical implications.

    Science.gov (United States)

    Chakraborty, Arpita

    2015-04-01

    The Deprivation of Liberty Safeguards were introduced in 2009 as an addition to the Mental Capacity Act 2005. This review discusses the legal impact of the Deprivation of Liberty Safeguards in the management of incapacitated patients.

  9. Anabolic androgenic steroid-induced hepatotoxicity.

    Science.gov (United States)

    Bond, Peter; Llewellyn, William; Van Mol, Peter

    2016-08-01

    Anabolic androgenic steroids (AAS) have been abused for decades by both professional and amateur athletes in order to improve physical performance or muscle mass. AAS abuse can cause adverse effects, among which are hepatotoxic effects. These effects include cholestatic icterus and possibly peliosis hepatis and hepatocellular carcinoma or adenoma. In particular, 17α-alkylated AAS appear to be hepatotoxic, whereas nonalkylated AAS appear not to be. The 17α-alkyl substitution retards hepatic metabolism of the AAS rendering it orally bioavailable. The mechanism responsible for the hepatotoxicity induced by 17α-alkylated AAS remains poorly understood. However, oxidative stress has been repeatedly shown to be associated with it. In this manuscript we present a hypothesis which describes a potential mechanism responsible for AAS-induced hepatotoxicity, based on several observations from the literature which suggest oxidative stress being a causal factor. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. [Control measures for anabolic androgenic steroid medicines].

    Science.gov (United States)

    Vázquez-Mourelle, Raquel; Carracedo-Martínez, Eduardo; Ces Gens, Eugenio; Cadórniga Valiño, Luis; Álvaro Esteban, Pilar; Pose Reino, José Manuel

    2015-01-01

    Anabolic androgenic steroids (AAS) can cause serious adverse effects when used without a therapeutic purpose. This article aims to show that the AAS are susceptible to being sold on the black market. We also aim to describe how certain limitations on the health inspection services of the Galician health service to pursue these illegal actions prompted a regulatory initiative demanding that additional actions be granted to community pharmacies when dispensing AAS. Four pharmacy inspections detected the diversion of a total of 3118 packages of AAS, which led to the opening of four disciplinary proceedings. In two of these, specialized police forces were called in as there was sufficient evidence of possible diversion to gymnasiums, resulting in a police operation called Operation Fitness. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  11. Occlusion for stimulus deprivation amblyopia

    Science.gov (United States)

    Antonio-Santos, Aileen; Vedula, Satyanarayana S; Hatt, Sarah R; Powell, Christine

    2014-01-01

    Background Stimulus deprivation amblyopia (SDA) develops due to an obstruction to the passage of light secondary to a condition such as cataract. The obstruction prevents formation of a clear image on the retina. SDA can be resistant to treatment, leading to poor visual prognosis. SDA probably constitutes less than 3% of all amblyopia cases, although precise estimates of prevalence are unknown. In developed countries, most patients present under the age of one year; in less developed parts of the world patients are likely to be older at the time of presentation. The mainstay of treatment is removal of the cataract and then occlusion of the better-seeing eye, but regimens vary, can be difficult to execute, and traditionally are believed to lead to disappointing results. Objectives Our objective was to evaluate the effectiveness of occlusion therapy for SDA in an attempt to establish realistic treatment outcomes. Where data were available, we also planned to examine evidence of any dose response effect and to assess the effect of the duration, severity, and causative factor on the size and direction of the treatment effect. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2013), EMBASE (January 1980 to October 2013), the Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2013), PubMed (January 1946 to October 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 28 October 2013. Selection criteria We planned

  12. Effects of Androgen Ablation on Anti-Tumor Immunity

    National Research Council Canada - National Science Library

    Kast, W

    2003-01-01

    ... prostate. Castration of mice stimulates B and T lymphopoiesis, thymic and bone marrow hyperplasia. The induction of apoptotic cell death following androgen ablation is accompanied by an inflammatory infiltrate comprised predominantly of activated T cells...

  13. Multiple arterial thromboses associated with anabolic androgenic steroids.

    Science.gov (United States)

    McCulloch, Neil Arthur; Abbas, Jonathan Raihan; Simms, Malcolm Harold

    2014-03-01

    The use of supraphysiological doses of anabolic androgenic steroids can have serious side effects. This article reports the case of a young man who suffered potentially life-threatening arterial thromboses following the use of these drugs.

  14. Androgen Receptor Splice Variants and Resistance to Taxane Chemotherapy

    Science.gov (United States)

    2016-10-01

    report. Inventions, patent applications, and/or licenses Nothing to report. Others Nothing to report. 7. Participants & Other... Brand LJ et al: Androgen receptor splice variants mediate enzalutamide resistance in castration-resistant prostate cancer cell lines. Cancer Res

  15. Regulation of Androgen Responses in Prostate Cancer by BAG-1

    National Research Council Canada - National Science Library

    Reed, John

    2001-01-01

    .... However, nearly all tumors eventually relapse as hormone-refractory disease. A need therefore exists for better understanding of the mechanisms that allow prostate cancer cells to grow in an androgen - independent manner...

  16. Regulation of Androgen Responses in Prostate Cancer by BAG-1

    National Research Council Canada - National Science Library

    Reed, John

    1999-01-01

    .... However, nearly all tumors eventually relapse as hormone- refractory disease. A need therefore exists for better understanding of the mechanisms that allow prostate cancer cells to grow in an androgen - independent manner...

  17. Performance of the Androgen Deficiency in Aging Male ...

    African Journals Online (AJOL)

    failure, chronic liver disease, chronic renal failure, tuberculosis, chronic obstructive pulmonary diseases, acquired immunodeficiency syndrome and malignancy. Relevant socio- demographic and diabetes-related information were documented. Clinical evaluation of androgen deficiency. Participants completed the original ...

  18. Male osteoporosis and androgenic therapy: from testosterone to SARMs.

    Science.gov (United States)

    Cilotti, Antonio; Falchetti, Alberto

    2009-09-01

    As in the women, male osteoporosis represents an important social problem, amplified by the increasing life expectance.Differently from women, 50% of male osteoporosis is secondary to treatments and/or diseases that make mandatory their search through an accurate clinical investigations in every newly diagnosed osteoporotic men. Male osteoporosis is frequently underdiagnosed and consequently undertreated, and too often it is revealed only after the occurrence of a fragility fracture. Androgens may prevent the loss of cancellous bone and stimulate periosteal cortical bone apposition. The anabolic effect of testosterone on both bone and muscle, is limited by the high incidence of androgenic side effects. Hypogonadism is the only situation where the benefits of the use of testosterone formulations exceed the side effects. Selective androgen receptor modulators can dissociate androgenic and anabolic effect on different tissues with various strategies. Many compounds have been studied with positive results in vivo and in clinical trials.

  19. Vocal cues to male androgen levels in giant pandas.

    Science.gov (United States)

    Charlton, Benjamin D; Keating, Jennifer L; Kersey, David; Rengui, Li; Huang, Yan; Swaisgood, Ronald R

    2011-02-23

    Little is known about the potential of non-human mammal vocalizations to signal information on the hormonal status of the caller. In the current study, we used endocrine data and acoustic analyses to determine whether male giant panda bleats provide reliable information about the caller's current androgen levels. Our results revealed significant relationships between acoustic features of male giant panda bleats and the caller's faecal androgen metabolite concentrations. To our knowledge, this constitutes the first demonstration that the acoustic structure of a non-human mammal call has the potential to yield information about the caller's current androgen levels. We go on to discuss the anatomical basis for our findings and the potential functional relevance of signalling information on male androgen levels in giant panda sexual communication.

  20. Molecular analysis of the androgen-receptor gene in a family with receptor-positive partial androgen insensitivity: an unusual type of intronic mutation

    NARCIS (Netherlands)

    H.T. Brüggenwirth (Hennie); A.L.M. Boehmer (Annemie); S. Ramnarain; M.C. Verleun-Mooijman; D.P.E. Satijn (David); J. Trapman (Jan); J.A. Grootegoed (Anton); A.O. Brinkmann (Albert)

    1997-01-01

    textabstractIn the coding part and the intron-exon boundaries of the androgen-receptor gene of a patient with partial androgen insensitivity, no mutation was found. The androgen receptor of this patient displayed normal ligand-binding parameters and migrated as a

  1. Sleep deprivation impairs cAMP signalling in the hippocampus

    NARCIS (Netherlands)

    Vecsey, Christopher G; Baillie, George S; Jaganath, Devan; Havekes, Robbert; Daniels, Andrew; Wimmer, Mathieu; Huang, Ted; Brown, Kim M; Li, Xiang-Yao; Descalzi, Giannina; Kim, Susan S; Chen, Tao; Shang, Yu-Ze; Zhuo, Min; Houslay, Miles D; Abel, Ted

    2009-01-01

    Millions of people regularly obtain insufficient sleep. Given the effect of sleep deprivation on our lives, understanding the cellular and molecular pathways affected by sleep deprivation is clearly of social and clinical importance. One of the major effects of sleep deprivation on the brain is to

  2. Impact of Early Postnatal Androgen Exposure on Voice Development

    Science.gov (United States)

    Grisa, Leila; Leonel, Maria L.; Gonçalves, Maria I. R.; Pletsch, Francisco; Sade, Elis R.; Custódio, Gislaine; Zagonel, Ivete P. S.; Longui, Carlos A.; Figueiredo, Bonald C.

    2012-01-01

    Background The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT) in childhood. Methods The long-term effects of androgen exposure on the fundamental vocal frequency (F0), vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years) and 10 adolescent (13.6 to 17.8 years) female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels. Results Of the 19 subjects, 17 (89%) had been diagnosed with ACT before 4 years of age, 1 (5%) at 8.16 years, and 1 (5%) at 10.75 years. Androgen exposure (2 to 30 months) was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19) of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz) and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz. Conclusions Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors. PMID:23284635

  3. Anabolic-androgenic steroids for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Iaquinto, G; Gluud, C

    2003-01-01

    Alcohol is one of the most common causes of liver disease in the Western World today. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease.......Alcohol is one of the most common causes of liver disease in the Western World today. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease....

  4. Androgen receptor and histone lysine demethylases in ovine placenta.

    Directory of Open Access Journals (Sweden)

    Ellane R Cleys

    Full Text Available Sex steroid hormones regulate developmental programming in many tissues, including programming gene expression during prenatal development. While estradiol is known to regulate placentation, little is known about the role of testosterone and androgen signaling in placental development despite the fact that testosterone rises in maternal circulation during pregnancy and in placenta-induced pregnancy disorders. We investigated the role of testosterone in placental gene expression, and focused on androgen receptor (AR. Prenatal androgenization decreased global DNA methylation in gestational day 90 placentomes, and increased placental expression of AR as well as genes involved in epigenetic regulation, angiogenesis, and growth. As AR complexes with histone lysine demethylases (KDMs to regulate AR target genes in human cancers, we also investigated if the same mechanism is present in the ovine placenta. AR co-immunoprecipitated with KDM1A and KDM4D in sheep placentomes, and AR-KDM1A complexes were recruited to a half-site for androgen response element (ARE in the promoter region of VEGFA. Androgenized ewes also had increased cotyledonary VEGFA. Finally, in human first trimester placental samples KDM1A and KDM4D immunolocalized to the syncytiotrophoblast, with nuclear KDM1A and KDM4D immunostaining also present in the villous stroma. In conclusion, placental androgen signaling, possibly through AR-KDM complex recruitment to AREs, regulates placental VEGFA expression. AR and KDMs are also present in first trimester human placenta. Androgens appear to be an important regulator of trophoblast differentiation and placental development, and aberrant androgen signaling may contribute to the development of placental disorders.

  5. Aberrant AR Signaling as a Function of Declining Androgen

    Science.gov (United States)

    2005-03-01

    Ser 133) obtained from the American Type Culture Collection located within a transcriptionally critical region called G\\’lanassas, VA, USA) and grown...p300 and its activation via the PIKA pathway. cells toward androgen independence with respect to Western blot data indicated that CREB phosphorylation...presence of obtained from the American Type Culture Collection (Manassas, V.A) and dihydrotestosterone after androgen receptor knock-down. We C4-2B

  6. Nonsteroidal Selective Androgen Receptor Modulators Enhance Female Sexual Motivation

    OpenAIRE

    Jones, Amanda; Hwang, Dong Jin; Duke, Charles B.; He, Yali; Siddam, Anjaiah; Miller, Duane D.; Dalton, James T.

    2010-01-01

    Women experience a decline in estrogen and androgen levels after natural or surgically induced menopause, effects that are associated with a loss of sexual desire and bone mineral density. Studies in our laboratories have shown the beneficial effects of selective androgen receptor modulators (SARMs) in the treatment of osteoporosis and muscle wasting in animal models. A series of S-3-(phenoxy)-2-hydroxy-2-methyl-N-(4-cyano-3-trifluoromethyl-phenyl)-propionamide analogs was synthesized to eval...

  7. Selective androgen receptor modulators in preclinical and clinical development

    OpenAIRE

    Narayanan, Ramesh; Mohler, Michael L.; Bohl, Casey E.; Miller, Duane D.; Dalton, James T.

    2008-01-01

    Androgen receptor (AR) plays a critical role in the function of several organs including primary and accessory sexual organs, skeletal muscle, and bone, making it a desirable therapeutic target. Selective androgen receptor modulators (SARMs) bind to the AR and demonstrate osteo- and myo-anabolic activity; however, unlike testosterone and other anabolic steroids, these nonsteroidal agents produce less of a growth effect on prostate and other secondary sexual organs. SARMs provide therapeutic o...

  8. CONDITIONED ANALYSIS OF HIGH-LATITUDE SOLAR WIND INTERMITTENCY

    International Nuclear Information System (INIS)

    D'Amicis, R.; Consolini, G.; Bavassano, B.; Bruno, R.

    2012-01-01

    The solar wind is a turbulent medium displaying intermittency. Its intermittent features have been widely documented and studied, showing how the intermittent character is different in fast and slow wind. In this paper, a statistical conditioned analysis of the solar wind intermittency for a period of high-latitude fast solar wind is presented. In particular, the intermittent features are investigated as a function of the Alfvénic degree of fluctuations at a given scale. The results show that the main contribution to solar wind intermittency is due to non-Alfvénic structures, while Alfvénic increments are found to be characterized by a smaller level of intermittency than the previous ones. Furthermore, the lifetime statistics of Alfvénic periods are discussed in terms of a multiscale texture of randomly oriented flux tubes.

  9. Relative Deprivation and the Gender Wage Gap.

    Science.gov (United States)

    Jackson, Linda A.

    1989-01-01

    Discusses how gender differences in the value of pay, based on relative deprivation theory, explain women's paradoxical contentment with lower wages. Presents a model of pay satisfaction to integrate value-based and comparative-referent explanations of the relationship between gender and pay satisfaction. Discusses economic approaches to the…

  10. Sleep deprivation impairs object recognition in mice

    NARCIS (Netherlands)

    Palchykova, S; Winsky-Sommerer, R; Meerlo, P; Durr, R; Tobler, Irene

    2006-01-01

    Many studies in animals and humans suggest that sleep facilitates learning, memory consolidation, and retrieval. Moreover, sleep deprivation (SD) incurred after learning, impaired memory in humans, mice, rats, and hamsters. We investigated the importance of sleep and its timing in in object

  11. Infant Face Preferences after Binocular Visual Deprivation

    Science.gov (United States)

    Mondloch, Catherine J.; Lewis, Terri L.; Levin, Alex V.; Maurer, Daphne

    2013-01-01

    Early visual deprivation impairs some, but not all, aspects of face perception. We investigated the possible developmental roots of later abnormalities by using a face detection task to test infants treated for bilateral congenital cataract within 1 hour of their first focused visual input. The seven patients were between 5 and 12 weeks old…

  12. Deprivation among unemployed South African youth ...

    African Journals Online (AJOL)

    a dedicated poverty survey conducted by Statistics South Africa from 2008 to 2009. Instead of focusing on the rather narrow income-poverty viewpoint, the study follows a multidimensional approach, using a range of social and material deprivation indicators to measure poverty. Results show that only transitory factors are ...

  13. Estrogens and Androgens in Skeletal Physiology and Pathophysiology

    Science.gov (United States)

    Almeida, Maria; Laurent, Michaël R.; Dubois, Vanessa; Claessens, Frank; O'Brien, Charles A.; Bouillon, Roger; Vanderschueren, Dirk

    2016-01-01

    Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably the landscape of our understanding of bone biology as well as the relationship between sex steroids and the physiology and pathophysiology of bone metabolism. Together with the appreciation of the side effects of estrogen-related therapies on breast cancer and cardiovascular diseases, these advances have also drastically altered the treatment of osteoporosis. In this article, we provide a comprehensive review of the molecular and cellular mechanisms of action of estrogens and androgens on bone, their influences on skeletal homeostasis during growth and adulthood, the pathogenetic mechanisms of the adverse effects of their deficiency on the female and male skeleton, as well as the role of natural and synthetic estrogenic or androgenic compounds in the pharmacotherapy of osteoporosis. We highlight latest advances on the crosstalk between hormonal and mechanical signals, the relevance of the antioxidant properties of estrogens and androgens, the difference of their cellular targets in different bone envelopes, the role of estrogen deficiency in male osteoporosis, and the contribution of estrogen or androgen deficiency to the monomorphic effects of aging on skeletal involution. PMID:27807202

  14. Anabolic-androgenic steroid increases running endurance in rats.

    Science.gov (United States)

    Van Zyl, C G; Noakes, T D; Lambert, M I

    1995-10-01

    The study was designed to determine whether treatment with an anabolic-androgenic steroid enhances running performance in rats by increasing their freely chosen training distance. Forty male Long-Evans rats were randomly divided into either a sedentary control group or an exercising group caged in specially designed running wheels in which the rats were able to run spontaneously. After 4 wk, both groups were further subdivided into two groups receiving either 0.5-mg Durabolin (nandrolone phenylpropionate) (im) or 0.5-mg saline, every second day. After 8 wk, running distance was similar in both exercising groups. Rats receiving the anabolic-androgenic steroid ran 41% longer during the test of submaximal running endurance compared to the trained rats receiving saline (P sedentary rats receiving the anabolic-androgenic steroid. After 4 wk of training, the maximal sprinting speed increased by 29% in trained rats. There was no further increase in maximal sprinting speed after an additional 4 wk of training and treatment with either anabolic-androgenic steroid or saline treatment. Therefore, rats that train spontaneously while being treated with an anabolic-androgenic steroid had increased submaximal running endurance compared with trained rats treated with saline, despite the similar voluntary training distance and skeletal muscle oxidative capacity between the two groups. The mechanism by which treatment with an anabolic-androgenic steroid, combined with training, enhances submaximal running performance could not be identified and needs to be addressed in future studies.

  15. Female adipocyte androgen synthesis and the effects of insulin

    Directory of Open Access Journals (Sweden)

    David Cadagan

    2014-01-01

    Full Text Available The metabolic syndrome is a cluster of metabolic disorders characterized by insulin resistance and hyperinsulinaemia, and its presence can increase the risk of cardiovascular disease significantly. The metabolic syndrome is associated with increased circulating androgen levels in women, which may originate from the ovaries and adrenal glands. Adipocytes are also able to synthesise steroid hormones, and this output has been hypothesised to increase with elevated insulin plasma concentrations. However, the contribution of the adipocytes to the circulating androgen levels in women with metabolic syndrome is limited and the effects of insulin are not fully understood. The aim of this study was to investigate the presence of steroid precursors and synthetic enzymes in human adipocyte biopsies as markers of possible adipocyte androgen synthesis. We examined pre and mature adipocytes taken from tissue biopsies of abdominal subcutaneous adipose tissue of participating women from the Department of Obstetrics and Gynaecology, of the Royal Derby Hospital. The results showed the potential for localised adipocyte androgen synthesis through the presence of the androgen precursor progesterone, as well as the steroid-converting enzyme 17α-hydroxylase. Furthermore, we found the controlled secretion of androstenedione in vitro and that insulin treatment caused levels to increase. Continued examination of a localised source of androgen production is therefore of clinical relevance due to its influence on adipocyte metabolism, its negative impact on female steroidogenic homeostasis, and the possible aggravation this may have when associated to obesity and obesity related metabolic abnormalities such as hyperinsulinaemia.

  16. Enhanced evaluation of selective androgen receptor modulators in vivo.

    Science.gov (United States)

    Otto-Duessel, M; He, M; Adamson, T W; Jones, J O

    2013-01-01

    Selective androgen receptor modulators (SARMs) are a class of drugs that control the activity of the androgen receptor (AR), which mediates the response to androgens, in a tissue-selective fashion. They are specifically designed to reduce the possible complications that result from the systemic inhibition or activation of AR in patients with diseases that involve androgen signalling. However, there are no ideal in vivo models for evaluating candidate SARMs. Therefore, we created a panel of androgen-responsive genes in clinically relevant AR expressing tissues including prostate, skin, bone, fat, muscle, brain and kidney. We used select genes from this panel to compare transcriptional changes in response to the full agonist dihydrotestosterone (DHT) and the SARM bolandiol at 16 h and 6 weeks. We identified several genes in each tissue whose expression at each of these time points correlates with the known tissue-specific effects of these compounds. For example, in the prostate we found four genes whose expression was much lower in animals treated with bolandiol compared with animals treated with DHT for 6 weeks, which correlated well with differences in prostate weight. We demonstrate that adding molecular measurements (androgen-regulated gene expression) to the traditional physiological measurements (tissue weights, etc.) makes the evaluation of potential SARMs more accurate, thorough and perhaps more rapid by allowing measurement of selectivity after only 16 h of drug treatment. © 2012 American Society of Andrology and European Academy of Andrology.

  17. Hormone Treatment and Muscle Anabolism during Aging: Androgens

    Science.gov (United States)

    Dillon, E. Lichar; Durham, William J.; Urban, Randall J.; Sheffield-Moore, Melinda

    2010-01-01

    Aging is associated with a gradual decline in circulating testosterone concentrations and decreased musculature in men. While testosterone administration is often considered when symptoms of hypogonadism are presented, the long-term effects of androgen use on muscle physiology are not yet fully understood. The definition of hypogonadism in men remains obscure but is generally indicated by total testosterone concentrations less than a threshold value of 300-500 ng/dL. Androgen replacement therapy is generally safe in men and women with low endogenous testosterone concentrations. The development of selective androgen receptor modulators (SARMs) may provide additional options in treatment of hypogonadism while lowering the potential of side effects often associated with long-term androgen use. Androgen administration, either alone or in combination with other treatments, can be successful in improving muscle mass by increasing protein anabolism and reducing protein catabolism in men and women. Further research is necessary to optimize the anabolic and anticatabolic properties of androgens for treatment and prevention of muscle loss in men and women. PMID:20452103

  18. Effects of sleep deprivation on cognition.

    Science.gov (United States)

    Killgore, William D S

    2010-01-01

    Sleep deprivation is commonplace in modern society, but its far-reaching effects on cognitive performance are only beginning to be understood from a scientific perspective. While there is broad consensus that insufficient sleep leads to a general slowing of response speed and increased variability in performance, particularly for simple measures of alertness, attention and vigilance, there is much less agreement about the effects of sleep deprivation on many higher level cognitive capacities, including perception, memory and executive functions. Central to this debate has been the question of whether sleep deprivation affects nearly all cognitive capacities in a global manner through degraded alertness and attention, or whether sleep loss specifically impairs some aspects of cognition more than others. Neuroimaging evidence has implicated the prefrontal cortex as a brain region that may be particularly susceptible to the effects of sleep loss, but perplexingly, executive function tasks that putatively measure prefrontal functioning have yielded inconsistent findings within the context of sleep deprivation. Whereas many convergent and rule-based reasoning, decision making and planning tasks are relatively unaffected by sleep loss, more creative, divergent and innovative aspects of cognition do appear to be degraded by lack of sleep. Emerging evidence suggests that some aspects of higher level cognitive capacities remain degraded by sleep deprivation despite restoration of alertness and vigilance with stimulant countermeasures, suggesting that sleep loss may affect specific cognitive systems above and beyond the effects produced by global cognitive declines or impaired attentional processes. Finally, the role of emotion as a critical facet of cognition has received increasing attention in recent years and mounting evidence suggests that sleep deprivation may particularly affect cognitive systems that rely on emotional data. Thus, the extent to which sleep deprivation

  19. Insights from intermittent binocular rivalry and EEG

    Directory of Open Access Journals (Sweden)

    Michael A Pitts

    2011-09-01

    Full Text Available Novel stimulation and analytical approaches employed in EEG studies of ambiguous figures have recently been applied to binocular rivalry. The combination of intermittent stimulus presentation and EEG source imaging has begun to shed new light on the neural underpinnings of binocular rivalry. Here, we review the basics of the intermittent paradigm and highlight methodological issues important for interpreting previous results and designing future experiments. We then outline current analytical approaches, including EEG microstates, event-related potentials, and statistically-based source estimation, and propose a spatio-temporal model that integrates findings from several studies. Finally, we discuss the advantages and limitations of using binocular rivalry as a tool to investigate the neural basis of perceptual awareness.

  20. Effects of vacusac in intermittent claudication

    DEFF Research Database (Denmark)

    Himmelstrup, H; Himmelstrup, Bodil; Mehlsen, J

    1991-01-01

    The effect of a new physical treatment modality, Vacusac, was tested on a group of patients with stable intermittent claudication. Twenty-two patients with a median age of 65 years and a median duration of intermittent claudication of 5 years were randomized to either active or placebo treatments....... Seventeen patients completed the study. The effect of treatment was quantified by measurements of systemic and peripheral systolic blood pressures and by measurements of the pain-free and the maximal walking distance on a treadmill. The ankle pressure index (ankle systolic pressure/arm systolic pressure......) and toe pressure index (toe systolic pressure/arm systolic pressure) were calculated. After 25 active treatments, administered over a period of 2 months, the patients allocated to this group attained a significant increase in the pain-free walking distance from 54 m (24-107 m) to 99 m (30-420 m) (P less...

  1. Intermittent character of interplanetary magnetic field fluctuations

    International Nuclear Information System (INIS)

    Bruno, Roberto; Carbone, Vincenzo; Chapman, Sandra; Hnat, Bogdan; Noullez, Alain; Sorriso-Valvo, Luca

    2007-01-01

    Interplanetary magnetic field magnitude fluctuations are notoriously more intermittent than velocity fluctuations in both fast and slow wind. This behavior has been interpreted in terms of the anomalous scaling observed in passive scalars in fully developed hydrodynamic turbulence. In this paper, the strong intermittent nature of the interplanetary magnetic field is briefly discussed comparing results performed during different phases of the solar cycle. The scaling properties of the interplanetary magnetic field magnitude show solar cycle variation that can be distinguished in the scaling exponents revealed by structure functions. The scaling exponents observed around the solar maximum coincide, within the errors, to those measured for passive scalars in hydrodynamic turbulence. However, it is also found that the values are not universal in the sense that the solar cycle variation may be reflected in dependence on the structure of the velocity field

  2. Intermittency exponent of the turbulent energy cascade

    International Nuclear Information System (INIS)

    Cleve, J.; Greiner, M.; Pearson, B.R.; Sreenivasan, K.R.

    2006-12-01

    We consider the turbulent energy dissipation from one-dimensional records in experiments using air and gaseous helium at cryogenic temperatures, and obtain the intermittency exponent via the two-point correlation function of the energy dissipation. The air data are obtained in a number of flows in a wind tunnel and the atmospheric boundary layer at a height of about 35 m above the ground. The helium data correspond to the centerline of a jet exhausting into a container. The air data on the intermittency exponent are consistent with each other and with a trend that increases with the Taylor microscale Reynolds number, R λ , of up to about 1000 and saturates thereafter. On the other hand, the helium data cluster around a constant value at nearly all R λ , this being about half of the asymptotic value for the air data. Some possible explanation is offered for this anomaly. (author)

  3. Optimal intermittent search strategies: smelling the prey

    International Nuclear Information System (INIS)

    Revelli, J A; Wio, H S; Rojo, F; Budde, C E

    2010-01-01

    We study the kinetics of the search of a single fixed target by a searcher/walker that performs an intermittent random walk, characterized by different states of motion. In addition, we assume that the walker has the ability to detect the scent left by the prey/target in its surroundings. Our results, in agreement with intuition, indicate that the prey's survival probability could be strongly reduced (increased) if the predator is attracted (or repelled) by the trace left by the prey. We have also found that, for a positive trace (the predator is guided towards the prey), increasing the inhomogeneity's size reduces the prey's survival probability, while the optimal value of α (the parameter that regulates intermittency) ceases to exist. The agreement between theory and numerical simulations is excellent.

  4. Downstream effects of intermittent power generation

    Energy Technology Data Exchange (ETDEWEB)

    Bretschko, G. (Austrian Academy of Sciences, Lunz (AT). Inst. fuer Limnologie); Moog, O. (Univ. Agric., Vienna (AT). Inst. Water Prov., Water Quality and Fisheries Management)

    1990-01-01

    Intermittent hydro-power generation creates frequent and dramatic discharge peaks combined with intervening extremely low water conditions downstream of the plant. Studies of the two Austrian rivers showed that whereas no alterations were found in the qualitative composition of zoobenthos, the decrease in abundance and biomass may amount up to 95%. The mismatch between the hydrography of surface water and groundwater might well be a cause of the detrimental effects of frequent and artificially created spates. The drastic reduction of zoobenthic biomass affects not only fish production but minimizes self-purification processes as well. Until tributaries diminish the effects of intermittent power generation, the river is reduced to a mere transport vehicle. (author).

  5. Intermittent preventive treatment of malaria in pregnancy

    DEFF Research Database (Denmark)

    Mbonye, A.K.; Bygbjerg, Ib Christian; Magnussen, Pascal

    2008-01-01

    OBJECTIVE: To assess whether traditional birth attendants, drug-shop vendors, community reproductive-health workers, or adolescent peer mobilizers could administer intermittent preventive treatment (IPTp) for malaria with sulfadoxine-pyrimethamine to pregnant women. METHODS: A non-randomized comm......OBJECTIVE: To assess whether traditional birth attendants, drug-shop vendors, community reproductive-health workers, or adolescent peer mobilizers could administer intermittent preventive treatment (IPTp) for malaria with sulfadoxine-pyrimethamine to pregnant women. METHODS: A non......, still births, and maternal and child deaths were secondary endpoints. FINDINGS: 1404 (67.5%) of 2081 with the new delivery system received two doses of sulfadoxine-pyrimethamine versus 281 (39.9%) of 704 with health units (P

  6. Further Evaluation of Androgen Therapy In Aplastic Anemia: With Special Reference to Correlation Between Response to Androgen and EEI

    International Nuclear Information System (INIS)

    Whang, Kee Suk

    1967-01-01

    Patients with aplastic anemia were treated with a combination of depo-testosterone cyclopentylpropionate (Upjohn) and dexamethasone. In 7 of 15 patients treated, there was response in which either a significant increase in hemoglobin concentration, a prolonged interval or a cessation of blood transfusion requirement developed during androgen therapy. Younger patients with cellular marrow appeared to be better responding to androgen. EEI (Effective Erythropoietic Index) formulated by Gardner and Nathan (1966) which was a helpful measurement as to whether patients with myelofibrosis would response to androgen, was evaluated in patients with aplastic anemia. It was concluded that EEI as well as ferrokinetics indices (Plasma- 59 Fe-disappearance rate, RBC 59 Fe net incorporation) did not significantly correlate with the degree of response to androgen in aplastic anemia.

  7. Long-range forecasting of intermittent streamflow

    OpenAIRE